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Conserved domains on  [gi|569005821|ref|XP_006531826|]
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calcium-binding protein 2 isoform X1 [Mus musculus]

Protein Classification

EF-hand domain-containing protein( domain architecture ID 11473824)

EF-hand (EFh) domain-containing protein similar to Homo sapiens guanylyl cyclase-activating proteins (GCAP1 and GCAP2), myosin regulatory light chain proteins, (MYL2, MYL5, MYL9, MYL10, and MYL12), and Kv channel-interacting proteins (KChIP1, KChIP2 and KChIP4)

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
166-324 6.92e-38

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


:

Pssm-ID: 227455 [Multi-domain]  Cd Length: 160  Bit Score: 132.43  E-value: 6.92e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 166 LRPSIAATQLDRElrpeEIEELQIAFQEFDRDRDGYIGYRELGACMRTLGYMPTEMELIEISQQISGGK--VDFEDFVEL 243
Cdd:COG5126    5 ISDLLTFTQLTEE----QIQELKEAFQLFDRDSDGLIDRNELGKILRSLGFNPSEAEINKLFEEIDAGNetVDFPEFLTV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 244 MGPKLLAETADmigvRELRDAFREFDTNGDGCISVGELRAALKAlLGERLSQREVDEILQDIDLNGDGLVDFEEFVRMMS 323
Cdd:COG5126   81 MSVKLKRGDKE----EELREAFKLFDKDHDGYISIGELRRVLKS-LGERLSDEEVEKLLKEYDEDGDGEIDYEEFKKLIK 155

                 .
gi 569005821 324 R 324
Cdd:COG5126  156 D 156
 
Name Accession Description Interval E-value
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
166-324 6.92e-38

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 227455 [Multi-domain]  Cd Length: 160  Bit Score: 132.43  E-value: 6.92e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 166 LRPSIAATQLDRElrpeEIEELQIAFQEFDRDRDGYIGYRELGACMRTLGYMPTEMELIEISQQISGGK--VDFEDFVEL 243
Cdd:COG5126    5 ISDLLTFTQLTEE----QIQELKEAFQLFDRDSDGLIDRNELGKILRSLGFNPSEAEINKLFEEIDAGNetVDFPEFLTV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 244 MGPKLLAETADmigvRELRDAFREFDTNGDGCISVGELRAALKAlLGERLSQREVDEILQDIDLNGDGLVDFEEFVRMMS 323
Cdd:COG5126   81 MSVKLKRGDKE----EELREAFKLFDKDHDGYISIGELRRVLKS-LGERLSDEEVEKLLKEYDEDGDGEIDYEEFKKLIK 155

                 .
gi 569005821 324 R 324
Cdd:COG5126  156 D 156
PTZ00184 PTZ00184
calmodulin; Provisional
178-322 4.24e-37

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 129.88  E-value: 4.24e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 178 ELRPEEIEELQIAFQEFDRDRDGYIGYRELGACMRTLGYMPTEMELIEISQQI---SGGKVDFEDFVELMGPKLlaetAD 254
Cdd:PTZ00184   4 QLTEEQIAEFKEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVdadGNGTIDFPEFLTLMARKM----KD 79
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569005821 255 MIGVRELRDAFREFDTNGDGCISVGELRAALKAlLGERLSQREVDEILQDIDLNGDGLVDFEEFVRMM 322
Cdd:PTZ00184  80 TDSEEEIKEAFKVFDRDGNGFISAAELRHVMTN-LGEKLTDEEVDEMIREADVDGDGQINYEEFVKMM 146
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
260-323 9.31e-24

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.


Pssm-ID: 238008 [Multi-domain]  Cd Length: 63  Bit Score: 92.23  E-value: 9.31e-24
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569005821 260 ELRDAFREFDTNGDGCISVGELRAALKALlGERLSQREVDEILQDIDLNGDGLVDFEEFVRMMS 323
Cdd:cd00051    1 ELREAFRLFDKDGDGTISADELKAALKSL-GEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63
EF-hand_7 pfam13499
EF-hand domain pair;
260-323 1.15e-18

EF-hand domain pair;


Pssm-ID: 433258 [Multi-domain]  Cd Length: 67  Bit Score: 78.45  E-value: 1.15e-18
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569005821  260 ELRDAFREFDTNGDGCISVGELRAALKALLGER-LSQREVDEILQDIDLNGDGLVDFEEFVRMMS 323
Cdd:pfam13499   3 KLKEAFKLLDKDGDGYLDVEELKKLLRKLEEGEpLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
260-288 2.13e-07

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 46.22  E-value: 2.13e-07
                           10        20
                   ....*....|....*....|....*....
gi 569005821   260 ELRDAFREFDTNGDGCISVGELRAALKAL 288
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29
 
Name Accession Description Interval E-value
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
166-324 6.92e-38

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 227455 [Multi-domain]  Cd Length: 160  Bit Score: 132.43  E-value: 6.92e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 166 LRPSIAATQLDRElrpeEIEELQIAFQEFDRDRDGYIGYRELGACMRTLGYMPTEMELIEISQQISGGK--VDFEDFVEL 243
Cdd:COG5126    5 ISDLLTFTQLTEE----QIQELKEAFQLFDRDSDGLIDRNELGKILRSLGFNPSEAEINKLFEEIDAGNetVDFPEFLTV 80
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 244 MGPKLLAETADmigvRELRDAFREFDTNGDGCISVGELRAALKAlLGERLSQREVDEILQDIDLNGDGLVDFEEFVRMMS 323
Cdd:COG5126   81 MSVKLKRGDKE----EELREAFKLFDKDHDGYISIGELRRVLKS-LGERLSDEEVEKLLKEYDEDGDGEIDYEEFKKLIK 155

                 .
gi 569005821 324 R 324
Cdd:COG5126  156 D 156
PTZ00184 PTZ00184
calmodulin; Provisional
178-322 4.24e-37

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 129.88  E-value: 4.24e-37
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 178 ELRPEEIEELQIAFQEFDRDRDGYIGYRELGACMRTLGYMPTEMELIEISQQI---SGGKVDFEDFVELMGPKLlaetAD 254
Cdd:PTZ00184   4 QLTEEQIAEFKEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVdadGNGTIDFPEFLTLMARKM----KD 79
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569005821 255 MIGVRELRDAFREFDTNGDGCISVGELRAALKAlLGERLSQREVDEILQDIDLNGDGLVDFEEFVRMM 322
Cdd:PTZ00184  80 TDSEEEIKEAFKVFDRDGNGFISAAELRHVMTN-LGEKLTDEEVDEMIREADVDGDGQINYEEFVKMM 146
PTZ00183 PTZ00183
centrin; Provisional
178-324 9.74e-27

centrin; Provisional


Pssm-ID: 185503 [Multi-domain]  Cd Length: 158  Bit Score: 102.85  E-value: 9.74e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 178 ELRPEEIEELQIAFQEFDRDRDGYIGYRELGACMRTLGYMPTEMELIEISQQI---SGGKVDFEDFVELMGPKLlaetad 254
Cdd:PTZ00183  10 GLTEDQKKEIREAFDLFDTDGSGTIDPKELKVAMRSLGFEPKKEEIKQMIADVdkdGSGKIDFEEFLDIMTKKL------ 83
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569005821 255 miGVRELRD----AFREFDTNGDGCISVGELRAALKAlLGERLSQREVDEILQDIDLNGDGLVDFEEFVRMMSR 324
Cdd:PTZ00183  84 --GERDPREeilkAFRLFDDDKTGKISLKNLKRVAKE-LGETITDEELQEMIDEADRNGDGEISEEEFYRIMKK 154
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
260-323 9.31e-24

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.


Pssm-ID: 238008 [Multi-domain]  Cd Length: 63  Bit Score: 92.23  E-value: 9.31e-24
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569005821 260 ELRDAFREFDTNGDGCISVGELRAALKALlGERLSQREVDEILQDIDLNGDGLVDFEEFVRMMS 323
Cdd:cd00051    1 ELREAFRLFDKDGDGTISADELKAALKSL-GEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63
EF-hand_7 pfam13499
EF-hand domain pair;
260-323 1.15e-18

EF-hand domain pair;


Pssm-ID: 433258 [Multi-domain]  Cd Length: 67  Bit Score: 78.45  E-value: 1.15e-18
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 569005821  260 ELRDAFREFDTNGDGCISVGELRAALKALLGER-LSQREVDEILQDIDLNGDGLVDFEEFVRMMS 323
Cdd:pfam13499   3 KLKEAFKLLDKDGDGYLDVEELKKLLRKLEEGEpLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
186-322 8.58e-16

Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds to Group I PEF proteins that have been found not only in higher animals but also in lower animals, plants, fungi and protists. Group I PEF proteins include apoptosis-linked gene 2 protein (ALG-2), peflin and similar proteins. ALG-2, also termed programmed cell death protein 6 (PDCD6), is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination. Peflin is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+.


Pssm-ID: 320055 [Multi-domain]  Cd Length: 164  Bit Score: 73.72  E-value: 8.58e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 186 ELQIAFQEFDRDRDGYIGYRELGACMRTLGYMPTEME----LIEISQQISGGKVDFEDFVELMGPkllaetadmigVREL 261
Cdd:cd16180    1 ELRRIFQAVDRDRSGRISAKELQRALSNGDWTPFSIEtvrlMINMFDRDRSGTINFDEFVGLWKY-----------IQDW 69
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569005821 262 RDAFREFDTNGDGCISVGELRAALKAlLGERLSQREVDEILQDIDLNGDGLVDFEEFVRMM 322
Cdd:cd16180   70 RRLFRRFDRDRSGSIDFNELQNALSS-FGYRLSPQFVQLLVRKFDRRRRGSISFDDFVEAC 129
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
182-274 7.41e-12

Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds to Group I PEF proteins that have been found not only in higher animals but also in lower animals, plants, fungi and protists. Group I PEF proteins include apoptosis-linked gene 2 protein (ALG-2), peflin and similar proteins. ALG-2, also termed programmed cell death protein 6 (PDCD6), is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination. Peflin is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+.


Pssm-ID: 320055 [Multi-domain]  Cd Length: 164  Bit Score: 62.55  E-value: 7.41e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 182 EEIEELQIAFQEFDRDRDGYIGYRELGACMRTLGYmptemeliEISQQIS-----------GGKVDFEDFVELmgpklla 250
Cdd:cd16180   64 KYIQDWRRLFRRFDRDRSGSIDFNELQNALSSFGY--------RLSPQFVqllvrkfdrrrRGSISFDDFVEA------- 128
                         90       100
                 ....*....|....*....|....
gi 569005821 251 etadMIGVRELRDAFREFDTNGDG 274
Cdd:cd16180  129 ----CVTLKRLTDAFRKYDTNRTG 148
PTZ00184 PTZ00184
calmodulin; Provisional
258-324 7.79e-12

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 62.09  E-value: 7.79e-12
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569005821 258 VRELRDAFREFDTNGDGCISVGELRAALKALlGERLSQREVDEILQDIDLNGDGLVDFEEFVRMMSR 324
Cdd:PTZ00184  10 IAEFKEAFSLFDKDGDGTITTKELGTVMRSL-GQNPTEAELQDMINEVDADGNGTIDFPEFLTLMAR 75
EFh_HEF cd15902
EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand ...
191-322 1.58e-11

EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand proteins family, also named the calbindin sub-family, contains a group of six EF-hand Ca2+-binding proteins, including calretinin (CR, also termed 29 kDa calbindin), calbindin D28K (CB, also termed vitamin D-dependent calcium-binding protein, avian-type), and secretagogin (SCGN). CR is a cytosolic hexa-EF-hand calcium-binding protein predominantly expressed in a variety of normal and tumorigenic t-specific neurons of the central and peripheral nervous system. It is a multifunctional protein implicated in many biological processes, including cell proliferation, differentiation, and cell death. CB is highly expressed in brain tissue. It is a strong calcium-binding and buffering protein responsible for preventing a neuronal death as well as maintaining and controlling calcium homeostasis. SCGN is a six EF-hand calcium-binding protein expressed in neuroendocrine, pancreatic endocrine and retinal cells. It plays a crucial role in cell apoptosis, receptor signaling and differentiation. It is also involved in vesicle secretion through binding to various proteins, including interacts with SNAP25, SNAP23, DOC2alpha, ARFGAP2, rootletin, KIF5B, beta-tubulin, DDAH-2, ATP-synthase and myeloid leukemia factor 2. SCGN functions as a Ca2+ sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. Although the family members share a significant amount of secondary sequence homology, they display altered structural and biochemical characteristics, and operate in distinct fashions. CB contains six EF-hand motifs in a single globular domain, where EF-hands 1, 3, 4, 5 bind four calcium ions. CR contains six EF-hand motifs within two independent domains, CR I-II and CR III-VI. They harbor two and four EF-hand motifs, respectively. The first 5 EF-hand motifs are capable of binding calcium ions, while the EF-hand 6 is inactive. SCGN consists of the three globular domains each of which contains a pair of EF-hand motifs. Human SCGN simultaneously binds four calcium ions through its EF-hands 3, 4, 5 and 6 in one high affinity and three low affinity calcium-binding sites. In contrast, SCGNs in other lower eukaryotes, such as D. rerio, X. laevis, M. domestica, G. gallus, O. anatinus, are fully competent in terms of six calcium-binding.


Pssm-ID: 320075 [Multi-domain]  Cd Length: 254  Bit Score: 63.53  E-value: 1.58e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 191 FQEFDRDRDGYIGYRELGACMRTL-----GYMPTEMELIEISQQI-------SGGKVDFEDFVELMGPK----LLAET-A 253
Cdd:cd15902    5 WMHFDADGNGYIEGKELDSFLRELlkalnGKDKTDDEVAEKKKEFmekydenEDGKIEIRELANILPTEenflLLFRReQ 84
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569005821 254 DMIGVRELRDAFREFDTNGDGCISVGELRAALKALL-------GERLSQREVDEILQDIDLNGDGLVDFEEFVRMM 322
Cdd:cd15902   85 PLISSVEFMKIWRKYDTDGSGFIEAKELKGFLKDLLlknkkhvSPPKLDEYTKLILKEFDANKDGKLELDEMAKLL 160
EF-hand_8 pfam13833
EF-hand domain pair;
272-324 4.02e-10

EF-hand domain pair;


Pssm-ID: 404678 [Multi-domain]  Cd Length: 54  Bit Score: 54.63  E-value: 4.02e-10
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|...
gi 569005821  272 GDGCISVGELRAALKALLGERLSQREVDEILQDIDLNGDGLVDFEEFVRMMSR 324
Cdd:pfam13833   1 EKGVITREELKRALALLGLKDLSEDEVDILFREFDTDGDGYISFDEFCVLLER 53
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
186-244 4.74e-10

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.


Pssm-ID: 238008 [Multi-domain]  Cd Length: 63  Bit Score: 54.86  E-value: 4.74e-10
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569005821 186 ELQIAFQEFDRDRDGYIGYRELGACMRTLGYMPTEMELIEISQQISG---GKVDFEDFVELM 244
Cdd:cd00051    1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKdgdGKIDFEEFLELM 62
EFh_CREC_RCN2_like cd16227
EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This ...
185-322 1.62e-09

EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This family corresponds to a group of uncharacterized RCN2-like proteins, which are mainly found in protostomes. Although their biological function remains unclear, they show high sequence similarity with RCN2 (also known as E6BP or TCBP-49), which is an endoplasmic reticulum resident low-affinity Ca2+-binding protein that has been implicated in immunity, redox homeostasis, cell cycle regulation and coagulation. Members in this family contain six copies of the EF-hand Ca2+-binding motif, but may lack a C-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide that is required for retention of RCN2 in the endoplasmic reticulum (ER).


Pssm-ID: 320025 [Multi-domain]  Cd Length: 263  Bit Score: 57.71  E-value: 1.62e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 185 EELQIAFQEFDRDRDGYIGYRELGAcmRTLGYMPTEME----------LIEISQ---------QISGGKVDFEDFVELMG 245
Cdd:cd16227   72 EEANERFEEADEDGDGKVTWEEYLA--DSFGYDDEDNEemikdsteddLKLLEDdkemfeaadLNKDGKLDKTEFSAFQH 149
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 246 PKllaETADMIGVrELRDAFREFDTNGDGCISVGELraalkalLGERLSQR-------EVDEILQDIDLNGDGLVDFEEF 318
Cdd:cd16227  150 PE---EYPHMHPV-LIEQTLRDKDKDNDGFISFQEF-------LGDRAGHEdkewllvEKDRFDEDYDKDGDGKLDGEEI 218

                 ....
gi 569005821 319 VRMM 322
Cdd:cd16227  219 LSWL 222
EFh_PEF_Group_II_sorcin_like cd16181
Penta-EF hand, calcium binding motifs, found in sorcin, grancalcin, and similar proteins; The ...
191-274 2.05e-09

Penta-EF hand, calcium binding motifs, found in sorcin, grancalcin, and similar proteins; The family corresponds to the second group of penta-EF hand (PEF) proteins that includes sorcin, grancalcin, and similar proteins. Sorcin, also termed 22 kDa Ca2+-binding protein, CP-22, or V19, is a soluble resistance-related calcium-binding protein that is expressed in normal mammalian tissues, such as the liver, lungs and heart. It contains a flexible glycine and proline-rich N-terminal extension and five EF-hand motifs that associate with membranes in a calcium-dependent manner. It may harbor three potential Ca2+ binding sites through its EF1, EF2 and EF3 hands. However, binding of only two Ca2+/monomer suffices to trigger the conformational change that exposes hydrophobic regions and leads to interaction with the respective targets. Sorcin forms homodimers through the association of the unpaired EF5 hand. Among the PEF proteins, sorcin is unique in that it contains potential phosphorylation sites by cAMP-dependent protein kinase (PKA), and it can form a tetramer at slightly acid pH values although remaining a stable dimer at neutral pH. Grancalcin (GCA) is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It can strongly interact with sorcin to form a heterodimer and further modulate the function of sorcin. GCA exists as homodimers in solution. It contains five EF-hand motifs attached to an N-terminal region of an approximately 50 residue-long segment rich in glycines and prolines. In contrast with sorcin, GCA binds two Ca2+ ions through its EF1 and EF3 hands.


Pssm-ID: 320056 [Multi-domain]  Cd Length: 165  Bit Score: 55.84  E-value: 2.05e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 191 FQEFDRDRDGYIGYRELGACMRTLGY--MPTEMELIeISQQISGGKVDFEDFVELmgpkllaetadMIGVRELRDAFREF 268
Cdd:cd16181   76 FMQYDRDRSGTVEPQELQQAIRSFGYnlSPQALNVI-VKRYSKNGRITFDDFVAC-----------AVRLRALTDRFRRR 143

                 ....*.
gi 569005821 269 DTNGDG 274
Cdd:cd16181  144 DTQQNG 149
EFh_CREC_Calumenin_like cd16226
EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 ...
178-319 2.34e-09

EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins; The family corresponds to a group of six EF-hand Ca2+-binding proteins, including calumenin (also known as crocalbin or CBP-50), reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins. Calumenin is an endo/sarcoplasmic reticulum (ER/SR) resident low-affinity Ca2+-binding protein that contains six EF-hand domains and a C-terminal SR retention signal His-Asp-Glu-Phe (HDEF) tetrapeptide. It functions as a novel regulator of SERCA2, and its expressional changes are tightly coupled with Ca2+-cycling of cardiomyocytes. It is also broadly involved in haemostasis and in the pathophysiology of thrombosis. Moreover, the extracellular calumenin acts as a suppressor of cell migration and tumor metastasis. RCN-1 is an endoplasmic reticulum resident Ca2+-binding protein with a carboxyl-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide signal. It acts as a potential negative regulator of B-RAF activation and can negatively modulate cardiomyocyte hypertrophy by inhibition of the mitogen-activated protein kinase signalling cascade. It also plays a key role in the development of doxorubicin-associated resistance. RCN-3 is a putative six EF-hand Ca2+-binding protein that contains five RXXR (X is any amino acid) motifs and a C-terminal ER retrieval signal HDEL tetrapeptide. The RXXR motif represents the target sequence of subtilisin-like proprotein convertases (SPCs). RCN-3 is specifically bound to the paired basic amino-acid-cleaving enzyme-4 (PACE4) precursor protein and plays an important role in the biosynthesis of PACE4.


Pssm-ID: 320024 [Multi-domain]  Cd Length: 264  Bit Score: 57.21  E-value: 2.34e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 178 ELRPEEIEE-LQIAFQEFDRDRDGYIgyrelgacmrtlgympTEMEL---IEISQQ----------------ISGGKVDF 237
Cdd:cd16226   27 QLTPEESKErLGIIVDKIDKNGDGFV----------------TEEELkdwIKYVQKkyiredvdrqwkeydpNKDGKLSW 90
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 238 EDFVELMGPKLLAETADMIGVRELRDA-------FREFDTNGDGCISVGELRAALKALLGERLSQREVDEILQDIDLNGD 310
Cdd:cd16226   91 EEYKKATYGFLDDEEEDDDLHESYKKMirrderrWKAADQDGDGKLTKEEFTAFLHPEEFPHMRDIVVQETLEDIDKNKD 170

                 ....*....
gi 569005821 311 GLVDFEEFV 319
Cdd:cd16226  171 GFISLEEYI 179
EF-hand_7 pfam13499
EF-hand domain pair;
184-244 3.46e-09

EF-hand domain pair;


Pssm-ID: 433258 [Multi-domain]  Cd Length: 67  Bit Score: 52.26  E-value: 3.46e-09
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569005821  184 IEELQIAFQEFDRDRDGYIGYRELGACMRTLGYM--PTEMELIEISQQI---SGGKVDFEDFVELM 244
Cdd:pfam13499   1 EEKLKEAFKLLDKDGDGYLDVEELKKLLRKLEEGepLSDEEVEELFKEFdldKDGRISFEEFLELY 66
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
187-323 7.01e-09

EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) isozymes; PI-PLC isozymes are signaling enzymes that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. This family corresponds to the four EF-hand motifs containing PI-PLC isozymes, including PI-PLC-beta (1-4), -gamma (1-2), -delta (1,3,4), -epsilon (1), -zeta (1), eta (1-2). Lower eukaryotes such as yeast and slime molds contain only delta-type isozymes. In contrast, other types of isoforms present in higher eukaryotes. This family also includes 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1 (PLC1) from fungi. Some homologs from plants contain only two atypical EF-hand motifs and they are not included. All PI-PLC isozymes except sperm-specific PI-PLC-zeta share a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. PI-PLC-zeta lacks the PH domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Most of EF-hand motifs found in PI-PLCs consist of a helix-loop-helix structure, but lack residues critical to metal binding. Moreover, the EF-hand region of most of PI-PLCs may have an important regulatory function, but it has yet to be identified. However, PI-PLC-zeta is a key exception. It is responsible for Ca2+ oscillations in fertilized oocytes and exhibits a high sensitivity to Ca2+ mediated through its EF-hand domain. In addition, PI-PLC-eta2 shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Also it appears that PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. PI-PLCs can be activated by a variety of extracellular ligands, such as growth factors, hormones, cytokines and lipids. Their activation has been implicated in tumorigenesis and/or metastasis linked to migration, proliferation, growth, inflammation, angiogenesis and actin cytoskeleton reorganization. PI-PLC-beta isozymes are activated by G-protein coupled receptor (GPCR) through different mechanisms. However, PI-PLC-gamma isozymes are activated by receptor tyrosine kinase (RTK), such as Rho and Ras GTPases. In contrast, PI-PLC-epsilon are activated by both GPCR and RTK. PI-PLC-delta1 and PLC-eta 1 are activated by GPCR-mediated calcium mobilization. The activation mechanism for PI-PLC-zeta remains unclear.


Pssm-ID: 320029 [Multi-domain]  Cd Length: 137  Bit Score: 53.44  E-value: 7.01e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 187 LQIAFQEFDRDRDGYIGYRELGACMRTLGYMPTEMELIEISQQI---SGGKVDFEDFVELMgpKLLAETAdmigvrELRD 263
Cdd:cd15898    2 LRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVdtnGDGTLTFDEFEELY--KSLTERP------ELEP 73
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569005821 264 AFREFDTNGDGCISVGELRAALKALLGERLSQREVDEILQDIDLNG-DGLVDFEEFVRMMS 323
Cdd:cd15898   74 IFKKYAGTNRDYMTLEEFIRFLREEQGENVSEEECEELIEKYEPEReNRQLSFEGFTNFLL 134
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
261-324 2.50e-08

EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) isozymes; PI-PLC isozymes are signaling enzymes that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. This family corresponds to the four EF-hand motifs containing PI-PLC isozymes, including PI-PLC-beta (1-4), -gamma (1-2), -delta (1,3,4), -epsilon (1), -zeta (1), eta (1-2). Lower eukaryotes such as yeast and slime molds contain only delta-type isozymes. In contrast, other types of isoforms present in higher eukaryotes. This family also includes 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1 (PLC1) from fungi. Some homologs from plants contain only two atypical EF-hand motifs and they are not included. All PI-PLC isozymes except sperm-specific PI-PLC-zeta share a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. PI-PLC-zeta lacks the PH domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Most of EF-hand motifs found in PI-PLCs consist of a helix-loop-helix structure, but lack residues critical to metal binding. Moreover, the EF-hand region of most of PI-PLCs may have an important regulatory function, but it has yet to be identified. However, PI-PLC-zeta is a key exception. It is responsible for Ca2+ oscillations in fertilized oocytes and exhibits a high sensitivity to Ca2+ mediated through its EF-hand domain. In addition, PI-PLC-eta2 shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Also it appears that PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. PI-PLCs can be activated by a variety of extracellular ligands, such as growth factors, hormones, cytokines and lipids. Their activation has been implicated in tumorigenesis and/or metastasis linked to migration, proliferation, growth, inflammation, angiogenesis and actin cytoskeleton reorganization. PI-PLC-beta isozymes are activated by G-protein coupled receptor (GPCR) through different mechanisms. However, PI-PLC-gamma isozymes are activated by receptor tyrosine kinase (RTK), such as Rho and Ras GTPases. In contrast, PI-PLC-epsilon are activated by both GPCR and RTK. PI-PLC-delta1 and PLC-eta 1 are activated by GPCR-mediated calcium mobilization. The activation mechanism for PI-PLC-zeta remains unclear.


Pssm-ID: 320029 [Multi-domain]  Cd Length: 137  Bit Score: 51.90  E-value: 2.50e-08
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569005821 261 LRDAFREFDTNGDGCISVGELRAALKALLGeRLSQREVDEILQDIDLNGDGLVDFEEFVRMMSR 324
Cdd:cd15898    2 LRRQWIKADKDGDGKLSLKEIKKLLKRLNI-RVSEKELKKLFKEVDTNGDGTLTFDEFEELYKS 64
EFh_CREC cd15899
EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin ...
183-319 5.49e-08

EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin/ERC45/calumenin)-EF hand family contains a group of six EF-hand, low-affinity Ca2+-binding proteins, including reticulocalbin (RCN-1), ER Ca2+-binding protein of 55 kDa (ERC-55, also known as TCBP-49 or E6BP), reticulocalbin-3 (RCN-3), Ca2+-binding protein of 45 kDa (Cab45 and its splice variant Cab45b), and calumenin ( also known as crocalbin or CBP-50). The proteins are not only localized in various parts of the secretory pathway, but also found in the cytosolic compartment and at the cell surface. They interact with different ligands or proteins and have been implicated in the secretory process, chaperone activity, signal transduction as well as in a large variety of disease processes.


Pssm-ID: 320021 [Multi-domain]  Cd Length: 267  Bit Score: 53.21  E-value: 5.49e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 183 EIEELQIAFQEFDRDRDGYIGYRELGAcmRTLGYmptemelieisqqisggKVDFEDFVELmGPKLLAETADMIgvRELR 262
Cdd:cd15899   69 AMEESKEQFRAVDPDEDGHVSWDEYKN--DTYGS-----------------VGDDEENVAD-NIKEDEEYKKLL--LKDK 126
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 569005821 263 DAFREFDTNGDGCISVGELRAALKALLGERLSQREVDEILQDIDLNGDGLVDFEEFV 319
Cdd:cd15899  127 KRFEAADQDGDLILTLEEFLAFLHPEESPYMLDFVIKETLEDLDKNGDGFISLEEFI 183
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
260-321 5.50e-08

EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein (ALG-2); The family includes some homologs of mammalian apoptosis-linked gene 2 protein (ALG-2) mainly found in lower eukaryotes, such as a parasitic protist Leishmarua major and a cellular slime mold Dictyostelium discoideum. These homologs contains five EF-hand motifs. Due to the presence of unfavorable residues at the Ca2+-coordinating positions, their non-canonical EF4 and EF5 hands may not bind Ca2+. Two Dictyostelium PEF proteins are the prototypes of this family. They may bind to cytoskeletal proteins and/or signal-transducing proteins localized to detergent-resistant membranes named lipid rafts, and occur as monomers or weak homo- or heterodimers like ALG-2. They can serve as a mediator for Ca2+ signaling-related Dictyostehum programmed cell death (PCD).


Pssm-ID: 320060 [Multi-domain]  Cd Length: 163  Bit Score: 51.45  E-value: 5.50e-08
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 569005821 260 ELRDAFREFDTNGDGCISVGELRAALkALLGERLSQREVDEILQDIDLNGDGLVDFEEFVRM 321
Cdd:cd16185    1 ELRQWFRAVDRDRSGSIDVNELQKAL-AGGGLLFSLATAEKLIRMFDRDGNGTIDFEEFAAL 61
EFh_PI-PLCdelta cd16202
EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta ...
261-324 5.59e-08

EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta isozymes represent a class of metazoan PI-PLCs that are some of the most sensitive to calcium among all PLCs. Their activation is modulated by intracellular calcium ion concentration, phospholipids, polyamines, and other proteins, such as RhoAGAP. Like other PI-PLC isozymes, PI-PLC-delta isozymes contain a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1, 3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Different PI-PLC-delta isozymes have different tissue distribution and different subcellular locations. PI-PLC-delta1 is mostly a cytoplasmic protein, PI-PLC-delta3 is located in the membrane, and PI-PLC-delta4 is predominantly detected in the cell nucleus. PI-PLC-delta isozymes is evolutionarily conserved even in non-mammalian species, such as yeast, slime molds and plants.


Pssm-ID: 320032 [Multi-domain]  Cd Length: 140  Bit Score: 51.07  E-value: 5.59e-08
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569005821 261 LRDAFREFDTNGDGCISVGELRAALKaLLGERLSQREVDEILQDIDLNGDGLVDFEEFV----RMMSR 324
Cdd:cd16202    2 LKDQFRKADKNGDGKLSFKECKKLLK-KLNVKVDKDYAKKLFQEADTSGEDVLDEEEFVqfynRLTKR 68
EFh_CREC_RCN3 cd16230
EF-hand, calcium binding motif, found in reticulocalbin-3 (RCN-3); RCN-3, also termed EF-hand ...
166-319 6.77e-08

EF-hand, calcium binding motif, found in reticulocalbin-3 (RCN-3); RCN-3, also termed EF-hand calcium-binding protein RLP49, is a putative six EF-hand Ca2+-binding protein that contains five RXXR (X is any amino acid) motifs and a C-terminal ER retrieval signal His-Asp-Glu-Leu (HDEL) tetrapeptide. The RXXR motif represents the target sequence of subtilisin-like proprotein convertases (SPCs). RCN-3 is specifically bound to the paired basic amino-acid-cleaving enzyme-4 (PACE4) precursor protein and plays an important role in the biosynthesis of PACE4.


Pssm-ID: 320028 [Multi-domain]  Cd Length: 268  Bit Score: 52.67  E-value: 6.77e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 166 LRPSIAATQlDRELRpeeiEELQIAFQEFDRDRDGYIGYRELgacmRTLGYmptemelieisqqisGGKVDFEDFVELMG 245
Cdd:cd16230   59 LRAWIAHTQ-QRHIR----DSVSAAWQTYDTDRDGRVGWEEL----RNATY---------------GHYEPGEEFHDVED 114
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569005821 246 PkllaETADMIGVRELRdAFREFDTNGDGCISVGELRAALKALLGERLSQREVDEILQDIDLNGDGLVDFEEFV 319
Cdd:cd16230  115 A----ETYKKMLARDER-RFRVADQDGDSMATREELTAFLHPEEFPHMRDIVVAETLEDLDKNKDGYVQVEEYI 183
EF-hand_6 pfam13405
EF-hand domain;
260-288 1.04e-07

EF-hand domain;


Pssm-ID: 433181 [Multi-domain]  Cd Length: 30  Bit Score: 47.17  E-value: 1.04e-07
                          10        20
                  ....*....|....*....|....*....
gi 569005821  260 ELRDAFREFDTNGDGCISVGELRAALKAL 288
Cdd:pfam13405   1 ELREAFKLFDKDGDGKISLEELRKALRSL 29
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
186-321 1.41e-07

EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein (ALG-2); The family includes some homologs of mammalian apoptosis-linked gene 2 protein (ALG-2) mainly found in lower eukaryotes, such as a parasitic protist Leishmarua major and a cellular slime mold Dictyostelium discoideum. These homologs contains five EF-hand motifs. Due to the presence of unfavorable residues at the Ca2+-coordinating positions, their non-canonical EF4 and EF5 hands may not bind Ca2+. Two Dictyostelium PEF proteins are the prototypes of this family. They may bind to cytoskeletal proteins and/or signal-transducing proteins localized to detergent-resistant membranes named lipid rafts, and occur as monomers or weak homo- or heterodimers like ALG-2. They can serve as a mediator for Ca2+ signaling-related Dictyostehum programmed cell death (PCD).


Pssm-ID: 320060 [Multi-domain]  Cd Length: 163  Bit Score: 50.29  E-value: 1.41e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 186 ELQIAFQEFDRDRDGYIGYRELGAcMRTLGYMP----TEMELIEISQQISGGKVDFEDFVELMgpKLLAEtadmigvreL 261
Cdd:cd16185    1 ELRQWFRAVDRDRSGSIDVNELQK-ALAGGGLLfslaTAEKLIRMFDRDGNGTIDFEEFAALH--QFLSN---------M 68
                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 262 RDAFREFDTNGDGCISVGELRAALkALLGERLSQREVDEILQDIDLNGDGLVDFEEFVRM 321
Cdd:cd16185   69 QNGFEQRDTSRSGRLDANEVHEAL-AASGFQLDPPAFQALFRKFDPDRGGSLGFDDYIEL 127
EFh_PEF cd15897
The penta-EF hand (PEF) family; The penta-EF hand (PEF) family contains a group of five ...
184-278 1.89e-07

The penta-EF hand (PEF) family; The penta-EF hand (PEF) family contains a group of five EF-hand calcium-binding proteins, including several classical calpain large catalytic subunits (CAPN1, 2, 3, 8, 9, 11, 12, 13, 14), two calpain small subunits (CAPNS1 and CAPNS2), as well as non-calpain PEF proteins, ALG-2 (apoptosis-linked gene 2, also termed programmed cell death protein 6, PDCD6), peflin, sorcin, and grancalcin. Based on the sequence similarity of EF1 hand, ALG-2 and peflin have been classified into group I PEF proteins. Calcium-dependent protease calpain subfamily members, sorcin and grancalcin, are group II PEF proteins. Calpains (EC 3.4.22.17) are calcium-activated intracellular cysteine proteases that play important roles in the degradation or functional modulation in a variety of substrates. They have been implicated in a number of physiological processes such as cell cycle progression, remodeling of cytoskeletal-cell membrane attachments, signal transduction, gene expression and apoptosis. ALG-2 is a pro-apoptotic factor that forms a homodimer in the cell or a heterodimer with its closest paralog peflin through their EF5s. Peflin is a 30-kD PEF protein with a longer N-terminal hydrophobic domain than any other member of the PEF family, and it contains nine nonapeptide (A/PPGGPYGGP) repeats. It exists only as a heterodimer with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+. ALG-2 interacts with various proteins in a Ca2+-dependent manner. Sorcin (for soluble resistance-related calcium binding protein) is a soluble resistance-related calcium-binding protein that participates in the regulation of calcium homeostasis in cells. Grancalcin is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It plays a key role in leukocyte-specific functions that are responsible for host defense. Grancalcin can form a heterodimer together with sorcin. Members in this family contain five EF-hand motifs attached to an N-terminal region of variable length containing one or more short Gly/Pro-rich sequences. These proteins form homodimers or heterodimers through pairing between the 5th EF-hands from the two molecules. Unlike calmodulin, the PEF domains do not undergo major conformational changes upon binding Ca2+.


Pssm-ID: 320054 [Multi-domain]  Cd Length: 165  Bit Score: 50.12  E-value: 1.89e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 184 IEELQIAFQEFDRDRDGYIGYRELGACMRTLGYMPTEMELIEISQQIS--GGKVDFEDFVELMgpkllaetadmIGVREL 261
Cdd:cd15897   69 IKAWQEIFRTYDTDGSGTIDSNELRQALSGAGYRLSEQTYDIIIRRYDrgRGNIDFDDFIQCC-----------VRLQRL 137
                         90
                 ....*....|....*..
gi 569005821 262 RDAFREFDTNGDGCISV 278
Cdd:cd15897  138 TDAFRRYDKDQDGQIQV 154
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
260-288 2.13e-07

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 46.22  E-value: 2.13e-07
                           10        20
                   ....*....|....*....|....*....
gi 569005821   260 ELRDAFREFDTNGDGCISVGELRAALKAL 288
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29
EFh_PEF_ALG-2 cd16183
EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar ...
184-279 2.37e-07

EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar proteins; ALG-2, also termed programmed cell death protein 6 (PDCD6), or probable calcium-binding protein ALG-2, is one of the prototypic members of the penta EF-hand protein family. It is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. ALG-2 acts as a pro-apoptotic factor participating in T cell receptor-, Fas-, and glucocorticoid-induced programmed cell death, and also serves as a useful molecular marker for the prognosis of cancers. Moreover, ALG-2 functions as a calcium ion sensor at endoplasmic reticulum (ER) exit sites, and modulates ER-stress-stimulated cell death and neuronal apoptosis during organ formation. Furthermore, ALG-2 can mediate the pro-apoptotic activity of cisplatin or tumor necrosis factor alpha (TNFalpha) through the down-regulation of nuclear factor-kappaB (NF-kappaB) expression. It also inhibits angiogenesis through PI3K/mTOR/p70S6K pathway by interacting of vascular endothelial growth factor receptor-2 (VEGFR-2). In addition, nuclear ALG-2 may participate in the post-transcriptional regulation of Inositol Trisphosphate Receptor Type 1 (IP3R1) pre-mRNA at least in part by interacting with CHERP (Ca2+ homeostasis endoplasmic reticulum protein) calcium-dependently. ALG-2 contains five serially repeated EF-hand motifs and interacts with various proteins, including ALG-2-interacting protein X (Alix), Fas, annexin XI, death-associated protein kinase 1 (DAPk1), Tumor susceptibility gene 101 (TSG101), Sec31A, phospholipid scramblase 3 (PLSCR3), the P-body component PATL1, and endosomal sorting complex required for transport (ESCRT)-III-related protein IST1, in a calcium-dependent manner. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination.


Pssm-ID: 320058 [Multi-domain]  Cd Length: 165  Bit Score: 49.56  E-value: 2.37e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 184 IEELQIAFQEFDRDRDGYIGYRELGACMRTLGY---MPTEMELIEISQQISGGKVDFEDFVELmgpkllaetadMIGVRE 260
Cdd:cd16183   66 ITDWQNCFRSFDRDNSGNIDKNELKQALTSFGYrlsDQFYDILVRKFDRQGRGTIAFDDFIQC-----------CVVLQT 134
                         90
                 ....*....|....*....
gi 569005821 261 LRDAFREFDTNGDGCISVG 279
Cdd:cd16183  135 LTDSFRRYDTDQDGWIQIS 153
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
297-324 2.47e-07

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 46.22  E-value: 2.47e-07
                           10        20
                   ....*....|....*....|....*...
gi 569005821   297 EVDEILQDIDLNGDGLVDFEEFVRMMSR 324
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKA 28
EFh_PEF_Group_II_CAPN_like cd16182
Penta-EF hand, calcium binding motifs, found in PEF calpain family; The PEF calpain family ...
233-324 2.47e-07

Penta-EF hand, calcium binding motifs, found in PEF calpain family; The PEF calpain family belongs to the second group of penta-EF hand (PEF) proteins. It includes classical (also called conventional or typical) calpain (referring to a calcium-dependent papain-like enzymes, EC 3.4.22.17) large catalytic subunits (CAPN1, 2, 3, 8, 9, 11, 12, 13, 14) and two calpain small subunits (CAPNS1 and CAPNS2), which are largely confined to animals (metazoans). These PEF-containing are nonlysosomal intracellular calcium-activated intracellular cysteine proteases that play important roles in the degradation or functional modulation in a variety of substrates in response to calcium signalling. The classical mu- and m-calpains are heterodimers consisting of homologous but a distinct (large) L-subunit/chain (CAPN1 or CAPN2) and a common (small) S-subunit/chain (CAPNS1 or CAPNS2). These L-subunits (CAPN1 and CAPN2) and S-subunit CAPNS1 are ubiquitously found in all tissues. Other calpains likely consist of an isolated L-subunit/chain alone. Many of them, such as CAPNS2, CAPN3 (in skeletal muscle, or lens), CAPN8 (in stomach), CAPN9 (in digestive tracts), CAPN11 (in testis), CAPN12 (in follicles), are tissue-specific and have specific functions in distinct organs. The L-subunits of similar structure (called CALPA and B) also have been found in Drosophila melanogaster. The S-subunit seems to have a chaperone-like function for proper folding of the L-subunit. The catalytic L-subunits contain a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain. The S-subunits only have the PEF domain following an N-terminal Gly-rich hydrophobic domain. The calpains undergo a rearrangement of the protein backbone upon Ca2+-binding.


Pssm-ID: 320057 [Multi-domain]  Cd Length: 167  Bit Score: 49.53  E-value: 2.47e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 233 GKVDFEDFVELMgpkllaetadmIGVRELRDAFREFDTNGDGCISVGELRAALKA-------LLGERLSQREVDEilqdi 305
Cdd:cd16182   57 GRLDLEEFKTLW-----------SDLKKWQAIFKKFDTDRSGTLSSYELRKALESagfhlsnKVLQALVLRYADS----- 120
                         90
                 ....*....|....*....
gi 569005821 306 dlngDGLVDFEEFVRMMSR 324
Cdd:cd16182  121 ----TGRITFEDFVSCLVR 135
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
260-288 3.02e-07

EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo calcium dependent conformational changes.


Pssm-ID: 425435 [Multi-domain]  Cd Length: 29  Bit Score: 45.85  E-value: 3.02e-07
                          10        20
                  ....*....|....*....|....*....
gi 569005821  260 ELRDAFREFDTNGDGCISVGELRAALKAL 288
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLKKL 29
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
297-324 7.44e-07

EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo calcium dependent conformational changes.


Pssm-ID: 425435 [Multi-domain]  Cd Length: 29  Bit Score: 44.70  E-value: 7.44e-07
                          10        20
                  ....*....|....*....|....*...
gi 569005821  297 EVDEILQDIDLNGDGLVDFEEFVRMMSR 324
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLKK 28
EFh_HEF cd15902
EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand ...
190-319 8.80e-07

EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand proteins family, also named the calbindin sub-family, contains a group of six EF-hand Ca2+-binding proteins, including calretinin (CR, also termed 29 kDa calbindin), calbindin D28K (CB, also termed vitamin D-dependent calcium-binding protein, avian-type), and secretagogin (SCGN). CR is a cytosolic hexa-EF-hand calcium-binding protein predominantly expressed in a variety of normal and tumorigenic t-specific neurons of the central and peripheral nervous system. It is a multifunctional protein implicated in many biological processes, including cell proliferation, differentiation, and cell death. CB is highly expressed in brain tissue. It is a strong calcium-binding and buffering protein responsible for preventing a neuronal death as well as maintaining and controlling calcium homeostasis. SCGN is a six EF-hand calcium-binding protein expressed in neuroendocrine, pancreatic endocrine and retinal cells. It plays a crucial role in cell apoptosis, receptor signaling and differentiation. It is also involved in vesicle secretion through binding to various proteins, including interacts with SNAP25, SNAP23, DOC2alpha, ARFGAP2, rootletin, KIF5B, beta-tubulin, DDAH-2, ATP-synthase and myeloid leukemia factor 2. SCGN functions as a Ca2+ sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. Although the family members share a significant amount of secondary sequence homology, they display altered structural and biochemical characteristics, and operate in distinct fashions. CB contains six EF-hand motifs in a single globular domain, where EF-hands 1, 3, 4, 5 bind four calcium ions. CR contains six EF-hand motifs within two independent domains, CR I-II and CR III-VI. They harbor two and four EF-hand motifs, respectively. The first 5 EF-hand motifs are capable of binding calcium ions, while the EF-hand 6 is inactive. SCGN consists of the three globular domains each of which contains a pair of EF-hand motifs. Human SCGN simultaneously binds four calcium ions through its EF-hands 3, 4, 5 and 6 in one high affinity and three low affinity calcium-binding sites. In contrast, SCGNs in other lower eukaryotes, such as D. rerio, X. laevis, M. domestica, G. gallus, O. anatinus, are fully competent in terms of six calcium-binding.


Pssm-ID: 320075 [Multi-domain]  Cd Length: 254  Bit Score: 49.27  E-value: 8.80e-07
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 190 AFQEFDRDRDGYIGYRELGACMRTL------GYMPTEM----ELIEISQQISG-GKVDFEDFVELMGPKL-LAETADMIG 257
Cdd:cd15902   95 IWRKYDTDGSGFIEAKELKGFLKDLllknkkHVSPPKLdeytKLILKEFDANKdGKLELDEMAKLLPVQEnFLLKFQILG 174
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 569005821 258 VRELR-----DAFREFDTNGDGCISVGELRAALKALLGERLSQREVDE-------ILQDIDLNGDGLVDFEEFV 319
Cdd:cd15902  175 AMDLTkedfeKVFEHYDKDNNGVIEGNELDALLKDLLEKNKADIDKPDlenfrdaILRACDKNKDGKIQKTELA 248
EFh_PI-PLCeta cd16205
EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes ...
261-323 9.18e-07

EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes represent a class of neuron-specific metazoan PI-PLCs that are most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. They are phosphatidylinositol 4,5-bisphosphate-hydrolyzing enzymes that are more sensitive to Ca2+ than other PI-PLC isozymes. They function as calcium sensors activated by small increases in intracellular calcium concentrations. They are also activated through G-protein-coupled receptor (GPCR) stimulation, and further mediate GPCR signalling pathways. PI-PLC-eta isozymes contain an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases. There are two PI-PLC-eta isozymes (1-2). Aside from the PI-PLC-eta isozymes identified in mammals, their eukaryotic homologs are also present in this family.


Pssm-ID: 320035 [Multi-domain]  Cd Length: 141  Bit Score: 47.38  E-value: 9.18e-07
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569005821 261 LRDAFREFDTNGDGCISVGELRAALKAlLGERLSQREVDEILQDIDL-NGDGLVDFEEFV---RMMS 323
Cdd:cd16205    2 LKQTFEEADKNGDGLLSIGEILQLMHK-LNVNLPRRKVRQMFKEADTdDNQGTLDFEEFCafyKMMS 67
EFh_PEF_peflin cd16184
EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed ...
190-279 1.96e-06

EF-hand, calcium binding motif, found in peflin and similar proteins; Peflin, also termed penta-EF hand (PEF) protein with a long N-terminal hydrophobic domain, or penta-EF hand domain-containing protein 1, is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+. In lower vertebrates, peflin may interact with transient receptor potential N (TRPN1), suggesting a potential role of peflin in fast transducer channel adaptation.


Pssm-ID: 320059 [Multi-domain]  Cd Length: 165  Bit Score: 47.26  E-value: 1.96e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 190 AFQEFDRDRDGYIGYRELGACMRTLGYMPTEM---ELIEISQQISGGKVDFEDFVELmgpkllaetadMIGVRELRDAFR 266
Cdd:cd16184   72 VFQQFDRDRSGSIDENELHQALSQMGYRLSPQfvqFLVSKYDPRARRSLTLDQFIQV-----------CVQLQSLTDAFR 140
                         90
                 ....*....|...
gi 569005821 267 EFDTNGDGCISVG 279
Cdd:cd16184  141 QRDTQMTGTITIS 153
EFh_PEF_CalpA_B cd16196
Penta-EF hand, calcium binding motifs, found in Drosophila melanogaster calpain-A (CalpA), ...
233-324 3.03e-06

Penta-EF hand, calcium binding motifs, found in Drosophila melanogaster calpain-A (CalpA), calpain-B (CalpB), and similar proteins; The family contains two calpains that have been found in Drosophila, CalpA and CalpB. CalpA, also termed calcium-activated neutral proteinase A (CANP A), or calpain-A catalytic subunit, is a Drosophila calpain homolog specifically expressed in a few neurons in the central nervous system, in scattered endocrine cells in the midgut, and in blood cells. CalpB, also termed calcium-activated neutral proteinase B (CANP B), contains calpain-B catalytic subunit 1 and calpain-B catalytic subunit 2. Both CalpA and CalpB are closely related to that of vertebrate calpains, and they share similar domain architecture, which consists of four domains: the N-terminal domain I, the catalytic domain II carrying the three active site residues, Cys, His and Asn, the Ca2+-regulated phospholipid-binding domain III, and penta-EF-hand Ca2+-binding domain IV. Besides, CalpA and CalpB display some distinguishing structural features that are not found in mammalian typical calpains. CalpA harbors a 76 amino acid long hydrophobic stretch inserted in domain IV, which may be involved in membrane attachment of this enzyme. CalpB has an unusually long N-terminal tail of 224 amino acids, which belongs to the class of intrinsically unstructured proteins (IUP) and may become ordered upon binding to target protein(s). Moreover, they do not need small regulatory subunits for their catalytic activity, and their proteolytic function is not regulated by an intrinsic inhibitor as the Drosophila genome contains neither regulatory subunit nor calpastatin orthologs. As a result, they may exist as a monomer or perhaps as a homo- or heterodimer together with a second large subunit. Furthermore, both CalpA and CalpB are dispensable for viability and fertility and do not share vital functions during Drosophila development. Phosphatidylinositol 4,5-diphosphate, phosphatidylinositol 4-monophosphate, phosphatidylinositol, and phosphatidic acid can stimulate the activity and the rate of activation of CalpA, but not CalpB. Calpain A modulates Toll responses by limited Cactus/IkappaB proteolysis. CalpB directly interacts with talin, an important component of the focal adhesion complex, and functions as an important modulator in border cell migration within egg chambers, which may act via the digestion of talin. CalpB can be phosphorylated by cAMP-dependent protein kinase (protein kinase A, PKA; EC 2.7.11.11) at Ser240 and Ser845, as well as by mitogen-activated protein kinase (ERK1 and ERK2; EC 2.7.11.24) at Thr747. The activation of the ERK pathway by extracellular signals results in the phosphorylation and activation of calpain B. In Schneider cells (S2), calpain B was mainly in the cytoplasm and upon a rise in Ca2+ the enzyme adhered to intracellular membranes.


Pssm-ID: 320071 [Multi-domain]  Cd Length: 167  Bit Score: 46.43  E-value: 3.03e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 233 GKVDFEDFVELMGpkllaetadmiGVRELRDAFREFDTNGDGCISVGELRAALKAlLGERLSQRevdeILQDIDL---NG 309
Cdd:cd16196   56 GKLGFEEFKKLWE-----------DLRSWKRVFKLFDTDGSGSFSSFELRNALNS-AGFRLSNA----TLNALVLrysNK 119
                         90
                 ....*....|....*
gi 569005821 310 DGLVDFEEFVRMMSR 324
Cdd:cd16196  120 DGRISFDDFIMCAVK 134
EFh_PEF cd15897
The penta-EF hand (PEF) family; The penta-EF hand (PEF) family contains a group of five ...
191-319 3.67e-06

The penta-EF hand (PEF) family; The penta-EF hand (PEF) family contains a group of five EF-hand calcium-binding proteins, including several classical calpain large catalytic subunits (CAPN1, 2, 3, 8, 9, 11, 12, 13, 14), two calpain small subunits (CAPNS1 and CAPNS2), as well as non-calpain PEF proteins, ALG-2 (apoptosis-linked gene 2, also termed programmed cell death protein 6, PDCD6), peflin, sorcin, and grancalcin. Based on the sequence similarity of EF1 hand, ALG-2 and peflin have been classified into group I PEF proteins. Calcium-dependent protease calpain subfamily members, sorcin and grancalcin, are group II PEF proteins. Calpains (EC 3.4.22.17) are calcium-activated intracellular cysteine proteases that play important roles in the degradation or functional modulation in a variety of substrates. They have been implicated in a number of physiological processes such as cell cycle progression, remodeling of cytoskeletal-cell membrane attachments, signal transduction, gene expression and apoptosis. ALG-2 is a pro-apoptotic factor that forms a homodimer in the cell or a heterodimer with its closest paralog peflin through their EF5s. Peflin is a 30-kD PEF protein with a longer N-terminal hydrophobic domain than any other member of the PEF family, and it contains nine nonapeptide (A/PPGGPYGGP) repeats. It exists only as a heterodimer with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+. ALG-2 interacts with various proteins in a Ca2+-dependent manner. Sorcin (for soluble resistance-related calcium binding protein) is a soluble resistance-related calcium-binding protein that participates in the regulation of calcium homeostasis in cells. Grancalcin is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It plays a key role in leukocyte-specific functions that are responsible for host defense. Grancalcin can form a heterodimer together with sorcin. Members in this family contain five EF-hand motifs attached to an N-terminal region of variable length containing one or more short Gly/Pro-rich sequences. These proteins form homodimers or heterodimers through pairing between the 5th EF-hands from the two molecules. Unlike calmodulin, the PEF domains do not undergo major conformational changes upon binding Ca2+.


Pssm-ID: 320054 [Multi-domain]  Cd Length: 165  Bit Score: 46.27  E-value: 3.67e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 191 FQEFDRDrDGYIGYRELGACMRTLGYMPTEME--------LIEISQQISGGKVDFEDFVELMGpKLLAetadmigvreLR 262
Cdd:cd15897    6 FQAVAGD-DGEISATELQQALSNVGWTHFDLGfsletcrsMIAMMDRDHSGKLNFSEFKGLWN-YIKA----------WQ 73
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 569005821 263 DAFREFDTNGDGCISVGELRAALKAlLGERLSQREVDEILQDIDlNGDGLVDFEEFV 319
Cdd:cd15897   74 EIFRTYDTDGSGTIDSNELRQALSG-AGYRLSEQTYDIIIRRYD-RGRGNIDFDDFI 128
EFh_calglandulin_like cd16252
EF-hand, calcium binding motif, found in uncharacterized calglandulin-like proteins; The ...
217-324 3.69e-06

EF-hand, calcium binding motif, found in uncharacterized calglandulin-like proteins; The family corresponds to a group of uncharacterized calglandulin-like proteins. Although their biological function remain unclear, they show high sequence similarity with human calglandulin-like protein GAGLP, which is an ortholog of calglandulin from the venom glands of Bothrops insularis snake. Both GAGLP and calglandulin are putative Ca2+-binding proteins with four EF-hand motifs. However, members in this family contain only three EF-hand motifs. In this point, they may belong to the parvalbumin-like EF-hand family, which is characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix).


Pssm-ID: 319995 [Multi-domain]  Cd Length: 106  Bit Score: 44.83  E-value: 3.69e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 217 MPTEMELieisqqisGGKVDFEDFVELMGPKLLAETADMIgvreLRDAFREFDTNGDGCISVGELRAALKALLGER---- 292
Cdd:cd16252    7 LPSEMRH--------HGSFNYSKFFEYMQKFQTSEQQEEA----IRKAFQMLDKDKSGFIEWNEIKYILSTVPSSMpvap 74
                         90       100       110
                 ....*....|....*....|....*....|..
gi 569005821 293 LSQREVDEILQDIDLNGDGLVDFEEFVRMMSR 324
Cdd:cd16252   75 LSDEEAEAMIQAADTDGDGRIDFQEFSDMVKK 106
EFh_PEF_ALG-2 cd16183
EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar ...
191-319 3.84e-06

EF-hand, calcium binding motif, found in apoptosis-linked gene 2 protein (ALG-2) and similar proteins; ALG-2, also termed programmed cell death protein 6 (PDCD6), or probable calcium-binding protein ALG-2, is one of the prototypic members of the penta EF-hand protein family. It is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. ALG-2 acts as a pro-apoptotic factor participating in T cell receptor-, Fas-, and glucocorticoid-induced programmed cell death, and also serves as a useful molecular marker for the prognosis of cancers. Moreover, ALG-2 functions as a calcium ion sensor at endoplasmic reticulum (ER) exit sites, and modulates ER-stress-stimulated cell death and neuronal apoptosis during organ formation. Furthermore, ALG-2 can mediate the pro-apoptotic activity of cisplatin or tumor necrosis factor alpha (TNFalpha) through the down-regulation of nuclear factor-kappaB (NF-kappaB) expression. It also inhibits angiogenesis through PI3K/mTOR/p70S6K pathway by interacting of vascular endothelial growth factor receptor-2 (VEGFR-2). In addition, nuclear ALG-2 may participate in the post-transcriptional regulation of Inositol Trisphosphate Receptor Type 1 (IP3R1) pre-mRNA at least in part by interacting with CHERP (Ca2+ homeostasis endoplasmic reticulum protein) calcium-dependently. ALG-2 contains five serially repeated EF-hand motifs and interacts with various proteins, including ALG-2-interacting protein X (Alix), Fas, annexin XI, death-associated protein kinase 1 (DAPk1), Tumor susceptibility gene 101 (TSG101), Sec31A, phospholipid scramblase 3 (PLSCR3), the P-body component PATL1, and endosomal sorting complex required for transport (ESCRT)-III-related protein IST1, in a calcium-dependent manner. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination.


Pssm-ID: 320058 [Multi-domain]  Cd Length: 165  Bit Score: 46.09  E-value: 3.84e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 191 FQEFDRDRDGYIGYRELGACMRTLGYMPTEME----LIEISQQISGGKVDFEDFVELMgpKLlaetadmigVRELRDAFR 266
Cdd:cd16183    6 FQRVDKDRSGQISATELQQALSNGTWTPFNPEtvrlMIGMFDRDNSGTINFQEFAALW--KY---------ITDWQNCFR 74
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 569005821 267 EFDTNGDGCISVGELRAALKAlLGERLSQREVDEILQDIDLNGDGLVDFEEFV 319
Cdd:cd16183   75 SFDRDNSGNIDKNELKQALTS-FGYRLSDQFYDILVRKFDRQGRGTIAFDDFI 126
EF-hand_6 pfam13405
EF-hand domain;
186-215 5.39e-06

EF-hand domain;


Pssm-ID: 433181 [Multi-domain]  Cd Length: 30  Bit Score: 42.55  E-value: 5.39e-06
                          10        20        30
                  ....*....|....*....|....*....|
gi 569005821  186 ELQIAFQEFDRDRDGYIGYRELGACMRTLG 215
Cdd:pfam13405   1 ELREAFKLFDKDGDGKISLEELRKALRSLG 30
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
186-214 5.83e-06

EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo calcium dependent conformational changes.


Pssm-ID: 425435 [Multi-domain]  Cd Length: 29  Bit Score: 42.39  E-value: 5.83e-06
                          10        20
                  ....*....|....*....|....*....
gi 569005821  186 ELQIAFQEFDRDRDGYIGYRELGACMRTL 214
Cdd:pfam00036   1 ELKEIFRLFDKDGDGKIDFEEFKELLKKL 29
EH cd00052
Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and ...
263-319 6.67e-06

Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and signal transduction. The alignment contains a pair of EF-hand motifs, typically one of them is canonical and binds to Ca2+, while the other may not bind to Ca2+. A hydrophobic binding pocket is formed by residues from both EF-hand motifs. The EH domain binds to proteins containing NPF (class I), [WF]W or SWG (class II), or H[TS]F (class III) sequence motifs.


Pssm-ID: 238009 [Multi-domain]  Cd Length: 67  Bit Score: 42.98  E-value: 6.67e-06
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 569005821 263 DAFREFDTNGDGCISVGELRAALKALlgeRLSQREVDEILQDIDLNGDGLVDFEEFV 319
Cdd:cd00052    3 QIFRSLDPDGDGLISGDEARPFLGKS---GLPRSVLAQIWDLADTDKDGKLDKEEFA 56
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
186-214 8.35e-06

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 41.98  E-value: 8.35e-06
                           10        20
                   ....*....|....*....|....*....
gi 569005821   186 ELQIAFQEFDRDRDGYIGYRELGACMRTL 214
Cdd:smart00054   1 ELKEAFRLFDKDGDGKIDFEEFKDLLKAL 29
EFh_HEF_CR cd16177
EF-hand, calcium binding motif, found in calretinin (CR); CR, also termed 29 kDa calbindin, is ...
191-322 1.40e-05

EF-hand, calcium binding motif, found in calretinin (CR); CR, also termed 29 kDa calbindin, is a cytosolic hexa-EF-hand calcium-binding protein predominantly expressed in a variety of normal and tumorigenic t specific neurons of the central and peripheral nervous system. It possibly functions as a calcium buffer, calcium sensor, and apoptosis regulator, which may be implicated in many biological processes, including cell proliferation, differentiation, and cell death. CR contains six EF-hand motifs within two independent domains, CR I-II and CR III-VI. CR I-II consists of EF-hand motifs 1 and 2, and CR III-VI consists of EF-hand motifs 3-6. The first 5 EF-hand motifs are capable of binding calcium ions, while the EF-hand 6 is inactive. Thus, CR has two pairs of cooperative binding sites (I-II and III-IV), which display high affinity calcium-binding sites, and one independent calcium ion-binding site (V), which displays lower affinity binding.


Pssm-ID: 320077 [Multi-domain]  Cd Length: 248  Bit Score: 45.64  E-value: 1.40e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 191 FQEFDRDRDGYIG-------YRELGACMRTLGYMPTEM-------ELIEISQQISGGKVDFEDFVELMGPK---LLAETA 253
Cdd:cd16177    5 WKHFDADGNGYIEgkelenfFRELERARRGAGVDSKSAnfgekmkEFMQKYDKNADGRIEMAELAQILPTEenfLLCFRQ 84
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569005821 254 DMIGVRELRDAFREFDTNGDGCISVGELRAALKALLgeRLSQREVDE---------ILQDIDLNGDGLVDFEEFVRMM 322
Cdd:cd16177   85 HVGSSSEFMEAWRKYDTDRSGYIEANELKGFLSDLL--KKANRPYDEkklqeytqtILRMFDLNGDGKLGLSEMARLL 160
S-100 cd00213
S-100: S-100 domain, which represents the largest family within the superfamily of proteins ...
272-322 1.77e-05

S-100: S-100 domain, which represents the largest family within the superfamily of proteins carrying the Ca-binding EF-hand motif. Note that this S-100 hierarchy contains only S-100 EF-hand domains, other EF-hands have been modeled separately. S100 proteins are expressed exclusively in vertebrates, and are implicated in intracellular and extracellular regulatory activities. Intracellularly, S100 proteins act as Ca-signaling or Ca-buffering proteins. The most unusual characteristic of certain S100 proteins is their occurrence in extracellular space, where they act in a cytokine-like manner through RAGE, the receptor for advanced glycation products. Structural data suggest that many S100 members exist within cells as homo- or heterodimers and even oligomers; oligomerization contributes to their functional diversification. Upon binding calcium, most S100 proteins change conformation to a more open structure exposing a hydrophobic cleft. This hydrophobic surface represents the interaction site of S100 proteins with their target proteins. There is experimental evidence showing that many S100 proteins have multiple binding partners with diverse mode of interaction with different targets. In addition to S100 proteins (such as S100A1,-3,-4,-6,-7,-10,-11,and -13), this group includes the ''fused'' gene family, a group of calcium binding S100-related proteins. The ''fused'' gene family includes multifunctional epidermal differentiation proteins - profilaggrin, trichohyalin, repetin, hornerin, and cornulin; functionally these proteins are associated with keratin intermediate filaments and partially crosslinked to the cell envelope. These ''fused'' gene proteins contain N-terminal sequence with two Ca-binding EF-hands motif, which may be associated with calcium signaling in epidermal cells and autoprocessing in a calcium-dependent manner. In contrast to S100 proteins, "fused" gene family proteins contain an extraordinary high number of almost perfect peptide repeats with regular array of polar and charged residues similar to many known cell envelope proteins.


Pssm-ID: 238131 [Multi-domain]  Cd Length: 88  Bit Score: 42.48  E-value: 1.77e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 569005821 272 GDGC-ISVGELRAALK----ALLGERLSQREVDEILQDIDLNGDGLVDFEEFVRMM 322
Cdd:cd00213   22 GDKDtLSKKELKELLEtelpNFLKNQKDPEAVDKIMKDLDVNKDGKVDFQEFLVLI 77
EFh_HEF_CBN cd16179
EF-hand, calcium binding motif, found in Drosophila melanogaster calbindin-32 (CBN) and ...
165-322 3.52e-05

EF-hand, calcium binding motif, found in Drosophila melanogaster calbindin-32 (CBN) and similar proteins; CBN, the product of the cbn gene, is a Drosophila homolog to vertebrate neuronal six EF-hand calcium binding proteins. It is expressed through most of ontogenesis with a selective distribution in the nervous system and in a few small adult thoracic muscles. Its precise biological role remains unclear. CBN contains six EF-hand motifs, but some of them may not bind calcium ions due to the lack of key residues.


Pssm-ID: 320079 [Multi-domain]  Cd Length: 261  Bit Score: 44.32  E-value: 3.52e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 165 FLRP---SIAATQLDRELRPE-EIEELQIAFQE-FDRDRDGYIGYRELGAcmrtlgYMPTEMELIEISQQisggKVDFED 239
Cdd:cd16179   24 FLREfvsSVNPEDVGPEVVSEtALEELKEEFMEaYDENQDGRIDIRELAQ------LLPTEENFLLLFRR----DNPLDS 93
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 240 FVELMgpkllaetadmigvrelrDAFREFDTNGDGCISVGELRAALKALLGErlSQREV-----------DEILQDIDLN 308
Cdd:cd16179   94 SVEFM------------------KVWREYDKDNSGYIEADELKNFLKHLLKE--AKRDNdvsedklieytDTILQLFDRN 153
                        170
                 ....*....|....
gi 569005821 309 GDGLVDFEEFVRMM 322
Cdd:cd16179  154 KDGKLQLSEMARLL 167
S-100A1 cd05025
S-100A1: S-100A1 domain found in proteins similar to S100A1. S100A1 is a calcium-binding ...
276-323 3.63e-05

S-100A1: S-100A1 domain found in proteins similar to S100A1. S100A1 is a calcium-binding protein belonging to a large S100 vertebrate-specific protein family within the EF-hand superfamily of calcium-binding proteins. Note that the S-100 hierarchy, to which this S-100A1 group belongs, contains only S-100 EF-hand domains, other EF-hands have been modeled separately. As is the case with many other members of S100 protein family, S100A1 is implicated in intracellular and extracellular regulatory activities, including interaction with myosin-associated twitchin kinase, actin-capping protein CapZ, sinapsin I, and tubulin. Structural data suggests that S100A1 proteins exist within cells as antiparallel homodimers, while heterodimers with S100A4 and S100B also has been reported. Upon binding calcium S100A1 changes conformation to expose a hydrophobic cleft which is the interaction site of S100A1 with its more that 20 known target proteins.


Pssm-ID: 240152 [Multi-domain]  Cd Length: 92  Bit Score: 41.80  E-value: 3.63e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 569005821 276 ISVGELRAALKALLGERL-SQRE---VDEILQDIDLNGDGLVDFEEFVRMMS 323
Cdd:cd05025   28 LSKKELKDLLQTELSDFLdAQKDadaVDKIMKELDENGDGEVDFQEFVVLVA 79
EFh_PEF_sorcin cd16187
Penta-EF hand, calcium binding motifs, found in sorcin; Sorcin, also termed 22 kDa Ca2 ...
191-277 4.16e-05

Penta-EF hand, calcium binding motifs, found in sorcin; Sorcin, also termed 22 kDa Ca2+-binding protein, CP-22, or V19, is a soluble resistance-related calcium-binding protein that is expressed in normal mammalian tissues, such as the liver, lungs and heart. The up-regulation of sorcin is correlated with a number of cancer types, including colorectal, gastric and breast cancer. It may represent a therapeutic target for reversing tumor multidrug resistance (MDR). Sorcin participates in the regulation of calcium homeostasis in cells and is necessary for the activation of mitosis and cytokinesis. It enhances metastasis and promotes epithelial-to-mesenchymal transition of colorectal cancer. Moreover, sorcin has been implicated in the regulation of intracellular Ca2+ cycling and cardiac excitation-contraction coupling. It displays the anti-apoptotic properties via the modulation of mitochondrial Ca2+ handling in cardiac myocytes. It can target and activate the sarcolemmal Na+/Ca2+ exchanger (NCX1) in cardiac muscle. Meanwhile, sorcin modulates cardiac L-type Ca2+ current by functional interaction with the alpha1C subunit. It also associates with calcium/calmodulin-dependent protein kinase IIdeltaC (CaMKIIdelta(C)) and further modulates ryanodine receptor (RyR) function in cardiac myocytes. Furthermore, sorcin may act as a Ca2+ sensor for glucose-induced nuclear translocation and the activation of carbohydrate-responsive element-binding protein (ChREBP)-dependent genes. As a mitochondrial chaperone TRAP1 interactor, sorcin involves in mitochondrial metabolism through the TRAP1 pathway. In addition, sorcin may regulate the inhibition of type I interferon response in cells through interacting with foot-and-mouth disease virus (FMDV) VP1. Sorcin contains a flexible glycine and proline-rich N-terminal extension and five EF-hand motifs that associate with membranes in a calcium-dependent manner. It may harbor three potential Ca2+ binding sites through its EF1, EF2 and EF3 hands. However, binding of only two Ca2+/monomer suffices to trigger the conformational change that exposes hydrophobic regions and leads to interaction with the respective targets. Sorcin forms homodimers through the association of the unpaired EF5 hand. Among the PEF proteins, sorcin is unique in that it contains potential phosphorylation sites by cAMP-dependent protein kinase (PKA), and it can form a tetramer at slightly acid pH values although remaining a stable dimer at neutral pH.


Pssm-ID: 320062 [Multi-domain]  Cd Length: 165  Bit Score: 43.36  E-value: 4.16e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 191 FQEFDRDRDGYIGYRELGACMRTLGYMPTEMELIEISQQIS-GGKVDFEDFVelmgpkllaetADMIGVRELRDAFREFD 269
Cdd:cd16187   76 FISFDSDRSGTVDPQELQKALTTMGFRLSPQAVNSIAKRYStNGKITFDDYI-----------ACCVKLRALTDSFRRRD 144

                 ....*...
gi 569005821 270 TNGDGCIS 277
Cdd:cd16187  145 TSQQGVVN 152
EFh_MICU cd15900
EF-hand, calcium binding motif, found in mitochondrial calcium uptake proteins MICU1, MICU2, ...
189-324 5.54e-05

EF-hand, calcium binding motif, found in mitochondrial calcium uptake proteins MICU1, MICU2, MICU3, and similar proteins; This family includes mitochondrial calcium uptake protein MICU1 and its two additional paralogs, MICU2 and MICU3. MICU1 localizes to the inner mitochondrial membrane (IMM). It functions as a gatekeeper of the mitochondrial calcium uniporter (MCU) and regulates MCU-mediated mitochondrial Ca2+ uptake, which is essential for maintaining mitochondrial homoeostasis. MICU1 and MICU2 are physically associated within the uniporter complex and are co-expressed across all tissues. They may play non-redundant roles in the regulation of the mitochondrial calcium uniporter. At present, the precise molecular function of MICU2 and MICU3 remain unclear. MICU2 may play possible roles in Ca2+ sensing and regulation of MCU, calcium buffering with a secondary impact on transport or assembly and stabilization of MCU. MICU3 likely has a role in mitochondrial calcium handling. All members in this family contains an N-terminal mitochondrial targeting sequence (MTS) as well as two evolutionarily conserved canonical Ca2+-binding EF-hands separated by a long stretch of residues predicted to form alpha-helices.


Pssm-ID: 320080 [Multi-domain]  Cd Length: 152  Bit Score: 42.60  E-value: 5.54e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 189 IAFQEFDRDRDGYIGYREL---------GACMRTLGYMPTEMELIEISQQiSG-----------GKVDFEDFVELMgPKL 248
Cdd:cd15900    4 IAFKMFDLDGDGELDKEEFnkvqsiirsQTSVGQRHRDHTNGESTKLGMN-STlaryffgkdgkQKLSIEKFLEFQ-ENL 81
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 569005821 249 LAETADMigvrelrDAFREFDTNGDGCISVGELRAALKALLGERLSQREVDEILQDIDLNGDGLVDFEEFVRMMSR 324
Cdd:cd15900   82 QEEIDDV-------DTALTFYHLAGASIDRKTFKRAAKVVAGVELSDHVVDVVFTIFDEDGDGILSHKEFISVMKD 150
EFh_HEF_CBN cd16179
EF-hand, calcium binding motif, found in Drosophila melanogaster calbindin-32 (CBN) and ...
191-322 5.81e-05

EF-hand, calcium binding motif, found in Drosophila melanogaster calbindin-32 (CBN) and similar proteins; CBN, the product of the cbn gene, is a Drosophila homolog to vertebrate neuronal six EF-hand calcium binding proteins. It is expressed through most of ontogenesis with a selective distribution in the nervous system and in a few small adult thoracic muscles. Its precise biological role remains unclear. CBN contains six EF-hand motifs, but some of them may not bind calcium ions due to the lack of key residues.


Pssm-ID: 320079 [Multi-domain]  Cd Length: 261  Bit Score: 43.94  E-value: 5.81e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 191 FQEFDRDRDGYIGYRELGACMRTL------GYMPTEMELIEISQQI-------SGGKVDFEDFVELMGPK------LLAE 251
Cdd:cd16179  101 WREYDKDNSGYIEADELKNFLKHLlkeakrDNDVSEDKLIEYTDTIlqlfdrnKDGKLQLSEMARLLPVKenflcrPIFK 180
                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 252 TADMIGVRELRDAFREFDTNGDGCISVGELRAALKALLgeRLSQREVDE---------ILQDIDLNGDGLVDFEEfVRMM 322
Cdd:cd16179  181 GAGKLTREDIDRVFALYDRDNNGTIENEELTGFLKDLL--ELVQEDYDEqdleefkeiILRGWDFNNDGKISRKE-LTML 257
EFh_MICU3 cd16175
EF-hand, calcium binding motif, found in calcium uptake protein 3, mitochondrial (MICU3) and ...
188-322 6.91e-05

EF-hand, calcium binding motif, found in calcium uptake protein 3, mitochondrial (MICU3) and similar proteins; MICU3, also termed EF-hand domain-containing family member A2 (EFHA2), is a paralog of MICU1 and notably found in the central nervous system (CNS) and skeletal muscle. At present, the precise molecular function of MICU3 remains unclear. It likely has a role in mitochondrial calcium handling. MICU3 contains an N-terminal mitochondrial targeting sequence (MTS) as well as two evolutionarily conserved canonical Ca2+-binding EF-hands separated by a long stretch of residues predicted to form alpha-helices.


Pssm-ID: 320083 [Multi-domain]  Cd Length: 128  Bit Score: 41.73  E-value: 6.91e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 188 QIAFQEFDRDRDGYIGYRE---LGACMRTLgymptemeLIEISQQISGGKVDFEDFVELMGpKLLAEtadmigVRELRDA 264
Cdd:cd16175    3 RIAFNMFDTDGNEMVDKKEflvLQEIFRTL--------LVHFFGKKGKAELNFEDFYRFMD-NLQTE------VEDFTIA 67
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 569005821 265 FREFdTNGDGCISVGELRAALKALLGERLSQREVDEILQDIDLNGDGLVDFEEFVRMM 322
Cdd:cd16175   68 MRMY-TFADRSISQDEFARAVKVCTGLKLSPHLVNTVFKIFDVDGDGQLSYKEFIGIM 124
S-100A10_like cd05031
S-100A10_like: S-100A10 domain found in proteins similar to S100A10. S100A10 is a member of ...
280-319 7.10e-05

S-100A10_like: S-100A10 domain found in proteins similar to S100A10. S100A10 is a member of the S100 family of EF-hand superfamily of calcium-binding proteins. Note that the S-100 hierarchy, to which this S-100A1_like group belongs, contains only S-100 EF-hand domains, other EF-hands have been modeled separately. S100 proteins are expressed exclusively in vertebrates, and are implicated in intracellular and extracellular regulatory activities. A unique feature of S100A10 is that it contains mutation in both of the calcium binding sites, making it calcium insensitive. S100A10 has been detected in brain, heart, gastrointestinal tract, kidney, liver, lung, spleen, testes, epidermis, aorta, and thymus. Structural data supports the homo- and hetero-dimeric as well as hetero-tetrameric nature of the protein. S100A10 has multiple binding partners in its calcium free state and is therefore involved in many diverse biological functions.


Pssm-ID: 240157 [Multi-domain]  Cd Length: 94  Bit Score: 40.87  E-value: 7.10e-05
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....
gi 569005821 280 ELRAALKALLGERL-SQRE---VDEILQDIDLNGDGLVDFEEFV 319
Cdd:cd05031   31 ELKKLMEKELSEFLkNQKDpmaVDKIMKDLDQNRDGKVNFEEFV 74
S-100Z cd05026
S-100Z: S-100Z domain found in proteins similar to S100Z. S100Z is a member of the S100 domain ...
276-323 7.15e-05

S-100Z: S-100Z domain found in proteins similar to S100Z. S100Z is a member of the S100 domain family within the EF-hand Ca2+-binding proteins superfamily. Note that the S-100 hierarchy, to which this S-100Z group belongs, contains only S-100 EF-hand domains, other EF-hands have been modeled separately.S100 proteins exhibit unique patterns of tissue- and cell type-specific expression and have been implicated in the Ca2+-dependent regulation of diverse physiological processes, including cell cycle regulation, differentiation, growth, and metabolic control. S100Z is normally expressed in various tissues, with its highest level of expression being in spleen and leukocytes. The function of S100Z remains unclear. Preliminary structural data suggests that S100Z is homodimer, however a heterodimer with S100P has been reported. S100Z is capable of binding calcium ions. When calcium binds to S110Z, the protein experiences a conformational change, which exposes hydrophobic surfaces on the protein. In comparison with their normal tissue counterparts, S100Z gene expression appears to be deregulated in some tumor tissues.


Pssm-ID: 240153 [Multi-domain]  Cd Length: 93  Bit Score: 41.01  E-value: 7.15e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 569005821 276 ISVGELRAALKALLGERL-SQRE---VDEILQDIDLNGDGLVDFEEFVRMMS 323
Cdd:cd05026   29 LSKGELKELLQRELTDFLsSQKDpmlVDKIMNDLDSNKDNEVDFNEFVVLVA 80
EFh_CREC_Calumenin_like cd16226
EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 ...
265-322 7.20e-05

EF-hand, calcium binding motif, found in calumenin, reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins; The family corresponds to a group of six EF-hand Ca2+-binding proteins, including calumenin (also known as crocalbin or CBP-50), reticulocalbin-1 (RCN-1), reticulocalbin-3 (RCN-3), and similar proteins. Calumenin is an endo/sarcoplasmic reticulum (ER/SR) resident low-affinity Ca2+-binding protein that contains six EF-hand domains and a C-terminal SR retention signal His-Asp-Glu-Phe (HDEF) tetrapeptide. It functions as a novel regulator of SERCA2, and its expressional changes are tightly coupled with Ca2+-cycling of cardiomyocytes. It is also broadly involved in haemostasis and in the pathophysiology of thrombosis. Moreover, the extracellular calumenin acts as a suppressor of cell migration and tumor metastasis. RCN-1 is an endoplasmic reticulum resident Ca2+-binding protein with a carboxyl-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide signal. It acts as a potential negative regulator of B-RAF activation and can negatively modulate cardiomyocyte hypertrophy by inhibition of the mitogen-activated protein kinase signalling cascade. It also plays a key role in the development of doxorubicin-associated resistance. RCN-3 is a putative six EF-hand Ca2+-binding protein that contains five RXXR (X is any amino acid) motifs and a C-terminal ER retrieval signal HDEL tetrapeptide. The RXXR motif represents the target sequence of subtilisin-like proprotein convertases (SPCs). RCN-3 is specifically bound to the paired basic amino-acid-cleaving enzyme-4 (PACE4) precursor protein and plays an important role in the biosynthesis of PACE4.


Pssm-ID: 320024 [Multi-domain]  Cd Length: 264  Bit Score: 43.73  E-value: 7.20e-05
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 569005821 265 FREFDTNGDGCISVGELRAALKaLLGERLSQREVDEILQDIDLNGDGLVDFEEFVRMM 322
Cdd:cd16226   41 VDKIDKNGDGFVTEEELKDWIK-YVQKKYIREDVDRQWKEYDPNKDGKLSWEEYKKAT 97
EFh_parvalbumin_like cd16251
EF-hand, calcium binding motif, found in parvalbumin-like EF-hand family; The family includes ...
233-321 7.79e-05

EF-hand, calcium binding motif, found in parvalbumin-like EF-hand family; The family includes alpha- and beta-parvalbumins, and a group of uncharacterized calglandulin-like proteins. Parvalbumins are small, acidic, cytosolic EF-hand-containing Ca2+-buffer and Ca2+ transporter/shuttle proteins belonging to EF-hand superfamily. They are expressed by vertebrates in fast-twitch muscle cells, specific neurons of the central and peripheral nervous system, sensory cells of the mammalian auditory organ (Corti's cell), and some other cells, and characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix) called AB, CD, and EF, but only CD and EF can chelate metal ions, such as Ca2+ and Mg2+. Thus, they may play an additional role in Mg2+ handling. Moreover, parvalbumins represent one of the major animal allergens. In metal-bound states, parvalbumins possess a rigid and stable tertiary structure and display strong allergenicity. In contrast, the metal-free parvalbumins are intrinsically disordered, and the loss of metal ions results in a conformational change that decreases their IgE binding capacity. Furthermore, parvalbumins have been widely used as a neuronal marker for a variety of functional brain systems. They also function as a Ca2+ shuttle transporting Ca2+ from troponin-C (TnC) to the sarcoplasmic reticulum (SR) Ca2+ pump during muscle relaxation. Thus they may facilitate myocardial relaxation and play important roles in cardiac diastolic dysfunction. Parvalbumins consists of alpha- and beta- sublineages, which can be distinguished on the basis of isoelectric point (pI > 5 for alpha; pI


Pssm-ID: 319994 [Multi-domain]  Cd Length: 101  Bit Score: 40.98  E-value: 7.79e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 233 GKVDFEDFVELMGpkLLAETADMIgvrelRDAFREFDTNGDGCISVGELRAALKAL--LGERLSQREVDEILQDIDLNGD 310
Cdd:cd16251   15 GSFNYKKFFEHVG--LKQKSEDQI-----KKVFQILDKDKSGFIEEEELKYILKGFsiAGRDLTDEETKALLAAGDTDGD 87
                         90
                 ....*....|.
gi 569005821 311 GLVDFEEFVRM 321
Cdd:cd16251   88 GKIGVEEFATL 98
EFh_PEF_CAPN13_14 cd16195
Penta-EF hand, calcium binding motifs, found in calpain-13 (CAPN13), calpain-14 (CAPN14), and ...
233-324 7.85e-05

Penta-EF hand, calcium binding motifs, found in calpain-13 (CAPN13), calpain-14 (CAPN14), and similar proteins; CAPN13, also termed calcium-activated neutral proteinase 13 (CANP 13), a 63.6 kDa calpain large subunit that exhibits a restricted tissue distribution with low levels of expression detected only in human testis and lung. In calpain family, CAPN13 is most closely related to calpain-14 (CAPN14). CAPN14, also termed calcium-activated neutral proteinase 14 (CANP 14), is a 76.7 kDa calpain large subunit that is most highly expressed in the oesophagus. Its expression and calpain activity can be induced by IL-13. Both CAPN13 and CAPN14 contain a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain.


Pssm-ID: 320070 [Multi-domain]  Cd Length: 168  Bit Score: 42.58  E-value: 7.85e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 233 GKVDFEDFVELMgpKLLaetadmigvRELRDAFREFDTNGDGCISVGELRAALKAlLGERLSqrevDEILQDIDL---NG 309
Cdd:cd16195   58 GRLSLEEFSRLW--KKL---------RKYKDIFQKADVSKSGFLSLSELRNAIQA-AGIRVS----DDLLNLMALrygDS 121
                         90
                 ....*....|....*
gi 569005821 310 DGLVDFEEFVRMMSR 324
Cdd:cd16195  122 SGRISFESFICLMLR 136
EFh_HEF_SCGN cd16178
EF-hand, calcium binding motif, found in secretagogin (SCGN); SCGN is a six EF-hand ...
191-323 7.94e-05

EF-hand, calcium binding motif, found in secretagogin (SCGN); SCGN is a six EF-hand calcium-binding protein expressed in neuroendocrine, pancreatic endocrine and retinal cells. It plays a crucial role in cell apoptosis, receptor signaling and differentiation. It is also involved in vesicle secretion through binding to various proteins, including interacts with SNAP25, SNAP23, DOC2alpha, ARFGAP2, rootletin, KIF5B, beta-tubulin, DDAH-2, ATP-synthase and myeloid leukemia factor 2. SCGN functions as a calcium sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. It also serves as a calcium buffer in neurons. Thus, SCGN may be linked to the pathogenesis of neurological diseases such as Alzheimer's, and also acts as a serum marker of neuronal damage, or as a tumor biomarker. SCGN consists of the three globular domains each of which contains a pair of EF-hand motifs. All six EF hand motifs of SCGN in some eukaryotes, including D. rerio, X. laevis, M. domestica, G. gallus, O. anatinus, could potentially bind six calcium ions. In contrast, SCGNs from higher eukaryotes have at least one non-functional EF-hand motif due to the mutation(s) or deletions. For instance, the EF1 loop does not coordinate calcium ion due to the key residue asparagine replaced by lysine in SCGNs of many mammalian species. Moreover, the EF2 loop seems to be competent for calcium-binding in most mammalian SCGNs except for human and chimpanzee orthologs.


Pssm-ID: 320078 [Multi-domain]  Cd Length: 257  Bit Score: 43.55  E-value: 7.94e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 191 FQEFDRDRDGYIGYRELGACMRTLGYM------PTEMELIEISQQISG-------GKVDFEDFVELMGPK------LLAE 251
Cdd:cd16178    5 WQHFDADESGYIEGKELDNFFKDLLKKlgtkdtISADEVQDVKECFMSaydvtgdGRIQIQELANIILPDdenfllFFRR 84
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569005821 252 TADMIGVRELRDAFREFDTNGDGCISVGELRAALKALL---GERLSQREVDE----ILQDIDLNGDGLVDFEEFVRMMS 323
Cdd:cd16178   85 EEPLDSSVEFMRIWRKYDADSSGYISAAELKNFLRDLFlqhKKVITEDKLDEytdtMMKIFDKNKDGRLDLNDMARILA 163
EF-hand_8 pfam13833
EF-hand domain pair;
231-288 1.10e-04

EF-hand domain pair;


Pssm-ID: 404678 [Multi-domain]  Cd Length: 54  Bit Score: 39.22  E-value: 1.10e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 569005821  231 SGGKVDFEDFVELMGPKLLAetadMIGVRELRDAFREFDTNGDGCISVGELRAALKAL 288
Cdd:pfam13833   1 EKGVITREELKRALALLGLK----DLSEDEVDILFREFDTDGDGYISFDEFCVLLERR 54
EF-hand_5 pfam13202
EF hand;
261-283 1.12e-04

EF hand;


Pssm-ID: 433035 [Multi-domain]  Cd Length: 25  Bit Score: 38.45  E-value: 1.12e-04
                          10        20
                  ....*....|....*....|...
gi 569005821  261 LRDAFREFDTNGDGCISVGELRA 283
Cdd:pfam13202   1 LKDTFRQIDLNGDGKISKEELRR 23
calgranulins cd05030
Calgranulins: S-100 domain found in proteins belonging to the Calgranulin subgroup of the S100 ...
295-324 1.58e-04

Calgranulins: S-100 domain found in proteins belonging to the Calgranulin subgroup of the S100 family of EF-hand calcium-modulated proteins, including S100A8, S100A9, and S100A12 . Note that the S-100 hierarchy, to which this Calgranulin group belongs, contains only S-100 EF-hand domains, other EF-hands have been modeled separately. These proteins are expressed mainly in granulocytes, and are involved in inflammation, allergy, and neuritogenesis, as well as in host-parasite response. Calgranulins are modulated not only by calcium, but also by other metals such as zinc and copper. Structural data suggested that calgranulins may exist in multiple structural forms, homodimers, as well as hetero-oligomers. For example, the S100A8/S100A9 complex called calprotectin plays important roles in the regulation of inflammatory processes, wound repair, and regulating zinc-dependent enzymes as well as microbial growth.


Pssm-ID: 240156 [Multi-domain]  Cd Length: 88  Bit Score: 40.02  E-value: 1.58e-04
                         10        20        30
                 ....*....|....*....|....*....|
gi 569005821 295 QREVDEILQDIDLNGDGLVDFEEFVRMMSR 324
Cdd:cd05030   50 QKAIDKIFEDLDTNQDGQLSFEEFLVLVIK 79
EFh_CREC_RCN1 cd16229
EF-hand, calcium binding motif, found in reticulocalbin-1 (RCN-1); RCN-1 is an endoplasmic ...
178-322 1.70e-04

EF-hand, calcium binding motif, found in reticulocalbin-1 (RCN-1); RCN-1 is an endoplasmic reticulum resident low-affinity Ca2+-binding protein with six EF-hand motifs and a carboxyl-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide signal. It is expressed at the cell surface. RCN-1 acts as a potential negative regulator of B-RAF activation and can negatively modulate cardiomyocyte hypertrophy by inhibition of the mitogen-activated protein kinase signaling cascade. It also plays a key role in the development of doxorubicin-associated resistance.


Pssm-ID: 320027 [Multi-domain]  Cd Length: 267  Bit Score: 42.56  E-value: 1.70e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 178 ELRPEEIEE-LQIAFQEFDRDRDGYIGYRELGACMRTLGYMPTEMELIEISQQI---SGGKVDFEDFVE------LMGPK 247
Cdd:cd16229   27 QLTPEESKErLGKIVDRIDDDKDGFVTTEELKAWIKRVQKRYIYENVAKVWKDYdlnKDNKISWEEYKQatygyyLGNPE 106
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 569005821 248 LLAETADMIGVREL--RDA--FREFDTNGDGCISVGELRAALKALLGERLSQREVDEILQDIDLNGDGLVDFEEFVRMM 322
Cdd:cd16229  107 EFQDATDQFSFKKMlpRDErrFKAADLDGDLAATREEFTAFLHPEEFEHMKDIVVLETLEDIDKNGDGFVDEDEYIADM 185
EFh_CREC_Calumenin cd16228
EF-hand, calcium binding motif, found in calumenin; Calumenin, also termed crocalbin, or IEF ...
178-322 2.26e-04

EF-hand, calcium binding motif, found in calumenin; Calumenin, also termed crocalbin, or IEF SSP 9302, is an endo/sarcoplasmic reticulum (ER/SR) resident low-affinity Ca2+-binding protein that contains six EF-hand domains and a C-terminal SR retention signal His-Asp-Glu-Phe (HDEF) tetrapeptide. It is highly expressed in various brain regions. Thus it plays an important role in migration and differentiation of neurons, and/or in Ca2+ signaling between glial cells and neurons. Calumenin is involved in Ca2+ homeostasis through interacting with ryanodine receptor RyR2 and SERCA2. It acts as a novel regulator of SERCA2, and its expressional changes are tightly coupled with Ca2+-cycling of cardiomyocytes. Calumenin also forms a Ca2+-dependent complex with thrombospondin-1, which is broadly involved in haemostasis and thrombosis. Moreover, calumenin is a molecular chaperone that endogenously regulates the vitamin K-dependent gamma-carboxylation of several proteins, including blood coagulation factors (such as FII, FVII, FIX, FX, and proteins C, S and Z), cell survival factors (Gas6) and bone metabolism proteins (such as matrix Gla protein or MGP, osteocalcin and periostin), through targeting the gamma-glutamyl carboxylase. It also functions as a charged F508del-cystic fibrosis transmembrane regulator (CFTR) folding modulator, as well as a G551D-CFTR associated protein. Furthermore, the extracellular calumenin acts as a suppressor of cell migration and tumor metastasis. It binds to and stabilizes fibulin-1, and further inactivates extracellular signal-regulated kinases 1 and 2 (ERK1/2) signaling.


Pssm-ID: 320026 [Multi-domain]  Cd Length: 263  Bit Score: 42.24  E-value: 2.26e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 178 ELRPEEIEE-LQIAFQEFDRDRDGYIGYRELGACMRtlgYMPTEMELIEISQQISG------GKVDFEDFVELMGPKLL- 249
Cdd:cd16228   27 QLTPEESKErLGKIVGKIDEDKDGFVTEDELKAWIK---FAQKRWIYEDVERQWKGhdlnedGLVSWEEYKNATYGYILd 103
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569005821 250 -AETADMIGVREL--RDA--FREFDTNGDGCISVGELRAALKALLGERLSQREVDEILQDIDLNGDGLVDFEEFVRMM 322
Cdd:cd16228  104 dPDPDDGFNYKQMmvRDErrFKMADKDGDLRATKEEFTAFLHPEEYDYMKDIVVLETMEDIDKNGDGFIDLEEYIGDM 181
EFh_PEF_CPNS1_2 cd16188
Penta-EF hand, calcium binding motifs, found in calcium-dependent protease small subunit ...
184-278 2.79e-04

Penta-EF hand, calcium binding motifs, found in calcium-dependent protease small subunit CAPNS1 and CAPNS2; CAPNS1, also termed calpain small subunit 1 (CSS1), or calcium-activated neutral proteinase small subunit (CANP small subunit), or calcium-dependent protease small subunit (CDPS), or calpain regulatory subunit, is a common 28-kDa regulatory calpain subunit encoded by the calpain small 1 (Capns1, also known as Capn4) gene. It acts as a binding partner to form a heterodimer with the 80 kDa calpain large catalytic subunit and is required in maintaining the activity of calpain. CAPNS1 plays a significant role in tumor progression of human cancer, and functions as a potential therapeutic target in human hepatocellular carcinoma (HCC), nasopharyngeal carcinoma (NPC), glioma, and clear cell renal cell carcinoma (ccRCC). It may be involved in regulating migration and cell survival through binding to the SH3 domain of Ras GTPase-activating protein (RasGAP). It may also modulate Akt/FoxO3A signaling and apoptosis through PP2A. CAPNS1 contains an N-terminal glycine rich domain and a C-terminal PEF-hand domain. CAPNS2, also termed calpain small subunit 2 (CSS2), is a novel tissue-specific 30 kDa calpain small subunit that lacks two oligo-Gly stretches characteristic of the N-terminal Gly-rich domain of CAPNS1. CAPNS2 acts as a chaperone for the calpain large subunit, and appears to be the functional equivalent of CAPNS1. However, CAPNS2 binds the large subunit much more weakly than CAPNS1 and it does not undergo the autolytic conversion typical of CAPNS1.


Pssm-ID: 320063 [Multi-domain]  Cd Length: 169  Bit Score: 40.88  E-value: 2.79e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 184 IEELQIAFQEFDRDRDGYIGYRELGACMRTLGYMPTEMELIEISQQIS--GGKVDFEDFVELMgpkllaetadmigVR-- 259
Cdd:cd16188   72 IKKWQGIYKQFDTDRSGTIGSQELPGAFEAAGFHLNEQLYQMIIRRYSdeDGNMDFDNFISCL-------------VRld 138
                         90
                 ....*....|....*....
gi 569005821 260 ELRDAFREFDTNGDGCISV 278
Cdd:cd16188  139 AMFRAFKSLDKDGTGQIQV 157
EFh_PI-PLCeta2 cd16221
EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also ...
261-323 2.81e-04

EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-2, or phosphoinositide phospholipase C-like 4, or phospholipase C-like protein 4 (PLC-L4), or phospholipase C-eta-2 (PLC-eta2), is a neuron-specific PI-PLC that is most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. It is also expressed in the pituitary gland, pineal gland, retina, and lung, as well as in neuroendocrine cells. PI-PLC-eta2 has been implicated in the regulation of neuronal differentiation/maturation. It is required for retinoic acid-stimulated neurite growth. It may also in part function downstream of G-protein-coupled receptors and play an important role in the formation and maintenance of the neuronal network in the postnatal brain. Moreover, PI-PLC-eta2 acts as a Ca2+ sensor that shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Its activation can be triggered either by intracellular calcium mobilization or by G beta-gamma signaling. PI-PLC-eta2 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases.


Pssm-ID: 320051 [Multi-domain]  Cd Length: 141  Bit Score: 40.30  E-value: 2.81e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569005821 261 LRDAFREFDTNGDGCISVGELRAALKAlLGERLSQREVDEILQDIDLNGD-GLVDFEEFV---RMMS 323
Cdd:cd16221    2 LKQTFDEADKNGDGSLSIGEVLQLLHK-LNVNLPRQKVKQMFKEADTDDNqGTLGFEEFCafyKMMS 67
EFh_CREC_RCN2_like cd16227
EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This ...
259-319 3.23e-04

EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This family corresponds to a group of uncharacterized RCN2-like proteins, which are mainly found in protostomes. Although their biological function remains unclear, they show high sequence similarity with RCN2 (also known as E6BP or TCBP-49), which is an endoplasmic reticulum resident low-affinity Ca2+-binding protein that has been implicated in immunity, redox homeostasis, cell cycle regulation and coagulation. Members in this family contain six copies of the EF-hand Ca2+-binding motif, but may lack a C-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide that is required for retention of RCN2 in the endoplasmic reticulum (ER).


Pssm-ID: 320025 [Multi-domain]  Cd Length: 263  Bit Score: 41.53  E-value: 3.23e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569005821 259 RELRDAFREFDTNGDGCISVGELRAALKALLgERLSQREVDEILQDIDLNGDGLVDFEEFV 319
Cdd:cd16227   36 RRLAVLAKKMDLNDDGFIDRKELKAWILRSF-KMLDEEEANERFEEADEDGDGKVTWEEYL 95
EF-hand_5 pfam13202
EF hand;
298-322 4.53e-04

EF hand;


Pssm-ID: 433035 [Multi-domain]  Cd Length: 25  Bit Score: 36.91  E-value: 4.53e-04
                          10        20
                  ....*....|....*....|....*
gi 569005821  298 VDEILQDIDLNGDGLVDFEEFVRMM 322
Cdd:pfam13202   1 LKDTFRQIDLNGDGKISKEELRRLL 25
EFh_PI-PLCeta1 cd16220
EF-hand motif found in phosphoinositide phospholipase C eta 1 (PI-PLC-eta1); PI-PLC-eta1, also ...
261-323 4.77e-04

EF-hand motif found in phosphoinositide phospholipase C eta 1 (PI-PLC-eta1); PI-PLC-eta1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-1, or phospholipase C-eta-1 (PLC-eta-1), or phospholipase C-like protein 3 (PLC-L3), is a neuron-specific PI-PLC that is most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. It is also expressed in the zona incerta and in the spinal cord. PI-PLC-eta1 may perform a fundamental role in the brain. It may also act in synergy with other PLC subtypes. For instance, it is activated via intracellular Ca2+ mobilization and then plays a role in the amplification of GPCR (G-protein-coupled receptor)-mediated PLC-beta signals. In addition, its activity can be stimulated by ionomycin. PI-PLC-eta1 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases.


Pssm-ID: 320050 [Multi-domain]  Cd Length: 141  Bit Score: 39.62  E-value: 4.77e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 569005821 261 LRDAFREFDTNGDGCISVGELRAALKAlLGERLSQREVDEILQDIDLNGD-GLVDFEEFV---RMMS 323
Cdd:cd16220    2 VKQTFEEADKNGDGLLNIEEIYQLMHK-LNVNLPRRKVRQMFQEADTDENqGTLTFEEFCvfyKMMS 67
Dockerin_I cd14256
Type I dockerin repeat domain; Bacterial cohesin domains bind to a complementary protein ...
269-314 8.86e-04

Type I dockerin repeat domain; Bacterial cohesin domains bind to a complementary protein domain named dockerin, and this interaction is required for the formation of the cellulosome, a cellulose-degrading complex. The cellulosome consists of scaffoldin, a noncatalytic scaffolding polypeptide, that comprises repeating cohesion modules and a single carbohydrate-binding module (CBM). Specific calcium-dependent interactions between cohesins and dockerins appear to be essential for cellulosome assembly. This subfamily represents type I dockerins, which are responsible for anchoring a variety of enzymatic domains to the complex.


Pssm-ID: 271215 [Multi-domain]  Cd Length: 57  Bit Score: 36.75  E-value: 8.86e-04
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 569005821 269 DTNGDGCISVGELRAALKALLGERLSQrevDEILQDIDLNGDGLVD 314
Cdd:cd14256    3 DVNGDGKVNSADAALLKKYLLGKITLT---EAQLKAADVNGDGKVN 45
ELC_N cd22949
N-terminal domain of Myosin essential light chain ELC; ELC is part of the apicomplexan ...
181-241 9.12e-04

N-terminal domain of Myosin essential light chain ELC; ELC is part of the apicomplexan membrane-associated protein complex called the glideosome, which is essential for parasite motility. The glideosome is composed of six proteins: myosin A (MyoA), essential light chain ELC, myosin light chain MLC1 (also called MTIP), and the glideosome-associated proteins GAP40, GAP45, and GAP50. MyoA is a Class XIV myosin implicated in gliding motility, as well as host cell and tissue invasion by parasites. ELC binds to the MyoA neck region adjacent to the MLC1-binding site, and both myosin light chains co-located to the glideosome. Although ELCs bind to a conserved MyoA sequence, P. falciparum ELC adopts a distinct structure in the free and MyoA-bound state. Therefore ELCs enhance MyoA performance by inducing alpha helical structure formation in MyoA and thus stiffening its lever arm. It has been shown that disruption of MyoA, MLC1, or ELC have dramatic effects on parasite motility but do not affect parasite shape or replication. The ELC N-terminal domain is part of the EF-hand calcium binding motif superfamily. Calcium binding has no effect on the structure of ELCs.


Pssm-ID: 439385 [Multi-domain]  Cd Length: 66  Bit Score: 36.94  E-value: 9.12e-04
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 569005821 181 PEEIEElqiAFQEFDRDRDGYIGYRELGACMRTLGYMPTEMELIEISQQISggKVDFEDFV 241
Cdd:cd22949    2 EEKFRE---AFILFDRDGDGELTMYEAVLAMRSCGIPLTNDEKDALPASMN--WDQFENWA 57
EFh_CREC_cab45 cd16225
EF-hand, calcium binding motif, found in 45 kDa calcium-binding protein (Cab45); Cab45, also ...
251-318 1.29e-03

EF-hand, calcium binding motif, found in 45 kDa calcium-binding protein (Cab45); Cab45, also termed stromal cell-derived factor 4 (SDF-4), is a soluble, lumenal Golgi resident low-affinity Ca2+-binding protein that contains six copies of the EF-hand Ca2+-binding motif. It is required for secretory pathway calcium ATPase1 (SPCA1)-dependent Ca2+ import into the trans-Golgi network (TGN) and plays an essential role in Ca2+-dependent secretory cargo sorting at the TGN.


Pssm-ID: 320023 [Multi-domain]  Cd Length: 278  Bit Score: 39.98  E-value: 1.29e-03
                         10        20        30        40        50        60        70
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 251 ETADMIGVRELRDAFREFDTNGDGCISVGELRAALKALLGERLSQ--REVDEILQDIDLNGDGLVDFEEF 318
Cdd:cd16225   26 EDSEPKKRKKLKEIFKKVDVNTDGFLSAEELEDWIMEKTQEHFQEavEENEQIFKAVDTDKDGNVSWEEY 95
EFh_parvalbumin_alpha cd16254
EF-hand, calcium binding motif, found in alpha-parvalbumin; Alpha-parvalbumin is cytosolic Ca2 ...
236-323 1.46e-03

EF-hand, calcium binding motif, found in alpha-parvalbumin; Alpha-parvalbumin is cytosolic Ca2+/Mg2+-binding protein expressed mainly in fast-twitch skeletal myofibrils, where it may act as a soluble relaxing factor facilitating the Ca2+-mediated relaxation phase. It is also expressed in rapidly firing neurons, particularly GABA-ergic neurons, and thus may confer protection against Ca2+ toxicity. The major role of alpha-parvalbumin is metal buffering and transport of Ca2+. It binds different metal cations, and exhibits very high affinity for Ca2+ and physiologically significant affinity for Mg2+. Alpha-parvalbumin is characterized by the presence of three consecutive EF-hand motifs (helix-loop-helix) called AB, CD, and EF, but only CD and EF can chelate metal ions, such as Ca2+ and Mg2+. Both metal ion-binding sites in alpha-parvalbumin are high-affinity sites. Additionally, in contrast to beta-parvalbumin, alpha-parvalbumin is less acidic and has an additional residue in the C-terminal helix.


Pssm-ID: 319997 [Multi-domain]  Cd Length: 101  Bit Score: 37.50  E-value: 1.46e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 236 DFEDFVELMGPKllAETADmigvrELRDAFREFDTNGDGCISVGELRAALKALL--GERLSQREVDEILQDIDLNGDGLV 313
Cdd:cd16254   18 DYKKFFEMVGLK--KKSAD-----DVKKVFHILDKDKSGFIEEDELKFVLKGFSpdGRDLSDKETKALLAAGDKDGDGKI 90
                         90
                 ....*....|
gi 569005821 314 DFEEFVRMMS 323
Cdd:cd16254   91 GIDEFATLVA 100
EFh_HEF_CB cd16176
EF-hand, calcium binding motif, found in calbindin (CB); CB, also termed calbindin D28, or ...
191-322 1.74e-03

EF-hand, calcium binding motif, found in calbindin (CB); CB, also termed calbindin D28, or D-28K, or avian-type vitamin D-dependent calcium-binding protein, is a unique intracellular calcium binding protein that functions as both a calcium sensor and buffer in eukaryotic cells, which undergoes a conformational change upon calcium binding and protects cells against insults of high intracellular calcium concentration. CB is highly expressed in brain and sensory neurons. It plays essential roles in neural functioning, altering synaptic interactions in the hippocampus, modulating calcium channel activity, calcium transients, and intrinsic neuronal firing activity. It prevents a neuronal death, as well as maintains and controls calcium homeostasis. CB also modulates the activity of proteins participating in the development of neurodegenerative disorders such as Alzheimer's disease, Huntington's disease, and bipolar disorder. Moreover, CB interacts with Ran-binding protein M, a protein known to involve in microtubule function. It also interacts with alkaline phosphatase and myo-inositol monophosphatase, as well as caspase 3, an enzyme that plays an important role in the regulation of apoptosis. CB contains six EF-hand motifs in a single globular domain, where EF-hands 1, 3, 4, 5 bind four calcium ions with high affinity.


Pssm-ID: 320076 [Multi-domain]  Cd Length: 243  Bit Score: 39.05  E-value: 1.74e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 191 FQEFDRDRDGYIGYRELGACMRTLGY--------MPTEME-LIEISQQISGGKVDFEDFVELMGPK---LLAETADMIGV 258
Cdd:cd16176    5 WHHYDNDGNGYIEGKELQSFIQELQQarkkagleLSDQMKaFVDQYGQSTDGKIGIVELAQILPTEenfLLFFRQQLKSS 84
                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 569005821 259 RELRDAFREFDTNGDGCISVGELRAALKALLGErlSQREVDE---------ILQDIDLNGDGLVDFEEFVRMM 322
Cdd:cd16176   85 EEFMQTWRKYDADHSGFIEADELKSFLKDLLKK--ANKPFDEskleeythtMLKMFDSNNDGKLGLTEMARLL 155
EFh_PEF_grancalcin cd16186
Penta-EF hand, calcium binding motifs, found in grancalcin; Grancalcin (GCA) is a cytosolic ...
191-270 1.82e-03

Penta-EF hand, calcium binding motifs, found in grancalcin; Grancalcin (GCA) is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It displays a Ca2+-dependent translocation to granules and plasma membrane upon neutrophil activation, suggesting roles in granule-membrane fusion and degranulation of neutrophils. It may also play a role in the regulation of vesicle/granule exocytosis through the reversible binding of secretory vesicles and plasma membranes upon the presence of calcium. Moreover, GCA is involved in inflammation, as well as in the process of adhesion of neutrophils to fibronectin. It plays a key role in leukocyte-specific functions that are responsible for host defense, and affects the function of integrin receptors on immune cells through binding to L-plastin in the absence of calcium. Furthermore, GCA can strongly interact with sorcin to form a heterodimer, and further modulate the function of sorcin. GCA exists as homodimers in solution. It contains five EF-hand motifs attached to an N-terminal region of an approximately 50 residue-long segment rich in glycines and prolines. GCA binds two Ca2+ ions through its EF1 and EF3 hands.


Pssm-ID: 320061 [Multi-domain]  Cd Length: 165  Bit Score: 38.31  E-value: 1.82e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 191 FQEFDRDRDGYIGYRELGACMRTLGYMPTEMELIEISQQIS-GGKVDFEDFVelmgpkllaetADMIGVRELRDAFREFD 269
Cdd:cd16186   76 FMTVDQDRSGTVEPHELRQAIGAMGYRLSPQTLTTIVKRYSkNGRIYFDDYV-----------ACCVKLRALTDFFRRRD 144

                 .
gi 569005821 270 T 270
Cdd:cd16186  145 H 145
EFh_PEF_CalpA_B cd16196
Penta-EF hand, calcium binding motifs, found in Drosophila melanogaster calpain-A (CalpA), ...
190-274 2.15e-03

Penta-EF hand, calcium binding motifs, found in Drosophila melanogaster calpain-A (CalpA), calpain-B (CalpB), and similar proteins; The family contains two calpains that have been found in Drosophila, CalpA and CalpB. CalpA, also termed calcium-activated neutral proteinase A (CANP A), or calpain-A catalytic subunit, is a Drosophila calpain homolog specifically expressed in a few neurons in the central nervous system, in scattered endocrine cells in the midgut, and in blood cells. CalpB, also termed calcium-activated neutral proteinase B (CANP B), contains calpain-B catalytic subunit 1 and calpain-B catalytic subunit 2. Both CalpA and CalpB are closely related to that of vertebrate calpains, and they share similar domain architecture, which consists of four domains: the N-terminal domain I, the catalytic domain II carrying the three active site residues, Cys, His and Asn, the Ca2+-regulated phospholipid-binding domain III, and penta-EF-hand Ca2+-binding domain IV. Besides, CalpA and CalpB display some distinguishing structural features that are not found in mammalian typical calpains. CalpA harbors a 76 amino acid long hydrophobic stretch inserted in domain IV, which may be involved in membrane attachment of this enzyme. CalpB has an unusually long N-terminal tail of 224 amino acids, which belongs to the class of intrinsically unstructured proteins (IUP) and may become ordered upon binding to target protein(s). Moreover, they do not need small regulatory subunits for their catalytic activity, and their proteolytic function is not regulated by an intrinsic inhibitor as the Drosophila genome contains neither regulatory subunit nor calpastatin orthologs. As a result, they may exist as a monomer or perhaps as a homo- or heterodimer together with a second large subunit. Furthermore, both CalpA and CalpB are dispensable for viability and fertility and do not share vital functions during Drosophila development. Phosphatidylinositol 4,5-diphosphate, phosphatidylinositol 4-monophosphate, phosphatidylinositol, and phosphatidic acid can stimulate the activity and the rate of activation of CalpA, but not CalpB. Calpain A modulates Toll responses by limited Cactus/IkappaB proteolysis. CalpB directly interacts with talin, an important component of the focal adhesion complex, and functions as an important modulator in border cell migration within egg chambers, which may act via the digestion of talin. CalpB can be phosphorylated by cAMP-dependent protein kinase (protein kinase A, PKA; EC 2.7.11.11) at Ser240 and Ser845, as well as by mitogen-activated protein kinase (ERK1 and ERK2; EC 2.7.11.24) at Thr747. The activation of the ERK pathway by extracellular signals results in the phosphorylation and activation of calpain B. In Schneider cells (S2), calpain B was mainly in the cytoplasm and upon a rise in Ca2+ the enzyme adhered to intracellular membranes.


Pssm-ID: 320071 [Multi-domain]  Cd Length: 167  Bit Score: 38.34  E-value: 2.15e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 190 AFQEFDRDRDGYIGYRELGACMRTLGYMPTEMELIEISQQISG--GKVDFEDFVELmgpkllaetadMIGVRELRDAFRE 267
Cdd:cd16196   76 VFKLFDTDGSGSFSSFELRNALNSAGFRLSNATLNALVLRYSNkdGRISFDDFIMC-----------AVKLKTMFEIFKE 144

                 ....*..
gi 569005821 268 FDTNGDG 274
Cdd:cd16196  145 KDPRGGG 151
EFh_HEF cd15902
EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand ...
263-322 2.28e-03

EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand proteins family, also named the calbindin sub-family, contains a group of six EF-hand Ca2+-binding proteins, including calretinin (CR, also termed 29 kDa calbindin), calbindin D28K (CB, also termed vitamin D-dependent calcium-binding protein, avian-type), and secretagogin (SCGN). CR is a cytosolic hexa-EF-hand calcium-binding protein predominantly expressed in a variety of normal and tumorigenic t-specific neurons of the central and peripheral nervous system. It is a multifunctional protein implicated in many biological processes, including cell proliferation, differentiation, and cell death. CB is highly expressed in brain tissue. It is a strong calcium-binding and buffering protein responsible for preventing a neuronal death as well as maintaining and controlling calcium homeostasis. SCGN is a six EF-hand calcium-binding protein expressed in neuroendocrine, pancreatic endocrine and retinal cells. It plays a crucial role in cell apoptosis, receptor signaling and differentiation. It is also involved in vesicle secretion through binding to various proteins, including interacts with SNAP25, SNAP23, DOC2alpha, ARFGAP2, rootletin, KIF5B, beta-tubulin, DDAH-2, ATP-synthase and myeloid leukemia factor 2. SCGN functions as a Ca2+ sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. Although the family members share a significant amount of secondary sequence homology, they display altered structural and biochemical characteristics, and operate in distinct fashions. CB contains six EF-hand motifs in a single globular domain, where EF-hands 1, 3, 4, 5 bind four calcium ions. CR contains six EF-hand motifs within two independent domains, CR I-II and CR III-VI. They harbor two and four EF-hand motifs, respectively. The first 5 EF-hand motifs are capable of binding calcium ions, while the EF-hand 6 is inactive. SCGN consists of the three globular domains each of which contains a pair of EF-hand motifs. Human SCGN simultaneously binds four calcium ions through its EF-hands 3, 4, 5 and 6 in one high affinity and three low affinity calcium-binding sites. In contrast, SCGNs in other lower eukaryotes, such as D. rerio, X. laevis, M. domestica, G. gallus, O. anatinus, are fully competent in terms of six calcium-binding.


Pssm-ID: 320075 [Multi-domain]  Cd Length: 254  Bit Score: 38.87  E-value: 2.28e-03
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 569005821 263 DAFREFDTNGDGCISVGELRAALKALLGERLSQREVDEILQDI--------DLNGDGLVDFEEFVRMM 322
Cdd:cd15902    3 EVWMHFDADGNGYIEGKELDSFLRELLKALNGKDKTDDEVAEKkkefmekyDENEDGKIEIRELANIL 70
EFh_PEF_Group_II_sorcin_like cd16181
Penta-EF hand, calcium binding motifs, found in sorcin, grancalcin, and similar proteins; The ...
198-319 3.22e-03

Penta-EF hand, calcium binding motifs, found in sorcin, grancalcin, and similar proteins; The family corresponds to the second group of penta-EF hand (PEF) proteins that includes sorcin, grancalcin, and similar proteins. Sorcin, also termed 22 kDa Ca2+-binding protein, CP-22, or V19, is a soluble resistance-related calcium-binding protein that is expressed in normal mammalian tissues, such as the liver, lungs and heart. It contains a flexible glycine and proline-rich N-terminal extension and five EF-hand motifs that associate with membranes in a calcium-dependent manner. It may harbor three potential Ca2+ binding sites through its EF1, EF2 and EF3 hands. However, binding of only two Ca2+/monomer suffices to trigger the conformational change that exposes hydrophobic regions and leads to interaction with the respective targets. Sorcin forms homodimers through the association of the unpaired EF5 hand. Among the PEF proteins, sorcin is unique in that it contains potential phosphorylation sites by cAMP-dependent protein kinase (PKA), and it can form a tetramer at slightly acid pH values although remaining a stable dimer at neutral pH. Grancalcin (GCA) is a cytosolic Ca2+-binding protein specifically expressed in neutrophils and monocytes/macrophages. It can strongly interact with sorcin to form a heterodimer and further modulate the function of sorcin. GCA exists as homodimers in solution. It contains five EF-hand motifs attached to an N-terminal region of an approximately 50 residue-long segment rich in glycines and prolines. In contrast with sorcin, GCA binds two Ca2+ ions through its EF1 and EF3 hands.


Pssm-ID: 320056 [Multi-domain]  Cd Length: 165  Bit Score: 37.74  E-value: 3.22e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 198 RDGYIGYRELGACMRTLG----YMPTEME----LIEISQQISGGKVDFEDFVELMGpkllaetadmiGVRELRDAFREFD 269
Cdd:cd16181   12 QDGQIDADELQRCLTQSGisgnYQPFSLEtcrlMIAMLDRDHSGKMGFNEFKELWA-----------ALNQWKTTFMQYD 80
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 569005821 270 TNGDGCISVGELRAALKAlLGERLSQREVDEILQDIDLNGDglVDFEEFV 319
Cdd:cd16181   81 RDRSGTVEPQELQQAIRS-FGYNLSPQALNVIVKRYSKNGR--ITFDDFV 127
EF-hand_5 pfam13202
EF hand;
187-211 3.32e-03

EF hand;


Pssm-ID: 433035 [Multi-domain]  Cd Length: 25  Bit Score: 34.22  E-value: 3.32e-03
                          10        20
                  ....*....|....*....|....*
gi 569005821  187 LQIAFQEFDRDRDGYIGYRELGACM 211
Cdd:pfam13202   1 LKDTFRQIDLNGDGKISKEELRRLL 25
EF-hand_8 pfam13833
EF-hand domain pair;
185-214 3.41e-03

EF-hand domain pair;


Pssm-ID: 404678 [Multi-domain]  Cd Length: 54  Bit Score: 34.98  E-value: 3.41e-03
                          10        20        30
                  ....*....|....*....|....*....|
gi 569005821  185 EELQIAFQEFDRDRDGYIGYRELGACMRTL 214
Cdd:pfam13833  25 DEVDILFREFDTDGDGYISFDEFCVLLERR 54
PLN02964 PLN02964
phosphatidylserine decarboxylase
269-323 4.00e-03

phosphatidylserine decarboxylase


Pssm-ID: 215520 [Multi-domain]  Cd Length: 644  Bit Score: 38.69  E-value: 4.00e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 569005821 269 DTNGDGCISVGELRAALKALlGERLSQREVDEILQDIDLNGDGLVDFEEFVRMMS 323
Cdd:PLN02964 189 DYDEDGQLSFSEFSDLIKAF-GNLVAANKKEELFKAADLNGDGVVTIDELAALLA 242
EFh_PEF_sorcin cd16187
Penta-EF hand, calcium binding motifs, found in sorcin; Sorcin, also termed 22 kDa Ca2 ...
198-319 6.23e-03

Penta-EF hand, calcium binding motifs, found in sorcin; Sorcin, also termed 22 kDa Ca2+-binding protein, CP-22, or V19, is a soluble resistance-related calcium-binding protein that is expressed in normal mammalian tissues, such as the liver, lungs and heart. The up-regulation of sorcin is correlated with a number of cancer types, including colorectal, gastric and breast cancer. It may represent a therapeutic target for reversing tumor multidrug resistance (MDR). Sorcin participates in the regulation of calcium homeostasis in cells and is necessary for the activation of mitosis and cytokinesis. It enhances metastasis and promotes epithelial-to-mesenchymal transition of colorectal cancer. Moreover, sorcin has been implicated in the regulation of intracellular Ca2+ cycling and cardiac excitation-contraction coupling. It displays the anti-apoptotic properties via the modulation of mitochondrial Ca2+ handling in cardiac myocytes. It can target and activate the sarcolemmal Na+/Ca2+ exchanger (NCX1) in cardiac muscle. Meanwhile, sorcin modulates cardiac L-type Ca2+ current by functional interaction with the alpha1C subunit. It also associates with calcium/calmodulin-dependent protein kinase IIdeltaC (CaMKIIdelta(C)) and further modulates ryanodine receptor (RyR) function in cardiac myocytes. Furthermore, sorcin may act as a Ca2+ sensor for glucose-induced nuclear translocation and the activation of carbohydrate-responsive element-binding protein (ChREBP)-dependent genes. As a mitochondrial chaperone TRAP1 interactor, sorcin involves in mitochondrial metabolism through the TRAP1 pathway. In addition, sorcin may regulate the inhibition of type I interferon response in cells through interacting with foot-and-mouth disease virus (FMDV) VP1. Sorcin contains a flexible glycine and proline-rich N-terminal extension and five EF-hand motifs that associate with membranes in a calcium-dependent manner. It may harbor three potential Ca2+ binding sites through its EF1, EF2 and EF3 hands. However, binding of only two Ca2+/monomer suffices to trigger the conformational change that exposes hydrophobic regions and leads to interaction with the respective targets. Sorcin forms homodimers through the association of the unpaired EF5 hand. Among the PEF proteins, sorcin is unique in that it contains potential phosphorylation sites by cAMP-dependent protein kinase (PKA), and it can form a tetramer at slightly acid pH values although remaining a stable dimer at neutral pH.


Pssm-ID: 320062 [Multi-domain]  Cd Length: 165  Bit Score: 36.81  E-value: 6.23e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 198 RDGYIGYRELGACMRTLG----YMPTEME----LIEISQQISGGKVDFEDFVELMgpkllaetadmIGVRELRDAFREFD 269
Cdd:cd16187   12 QDGQIDADELQRCLTQSGiaggYKPFNLEtcrlMISMLDRDMSGTMGFNEFKELW-----------AVLNGWRQHFISFD 80
                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|
gi 569005821 270 TNGDGCISVGELRAALKAlLGERLSQREVDEILQDIDLNGDglVDFEEFV 319
Cdd:cd16187   81 SDRSGTVDPQELQKALTT-MGFRLSPQAVNSIAKRYSTNGK--ITFDDYI 127
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
187-278 7.05e-03

EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein (ALG-2); The family includes some homologs of mammalian apoptosis-linked gene 2 protein (ALG-2) mainly found in lower eukaryotes, such as a parasitic protist Leishmarua major and a cellular slime mold Dictyostelium discoideum. These homologs contains five EF-hand motifs. Due to the presence of unfavorable residues at the Ca2+-coordinating positions, their non-canonical EF4 and EF5 hands may not bind Ca2+. Two Dictyostelium PEF proteins are the prototypes of this family. They may bind to cytoskeletal proteins and/or signal-transducing proteins localized to detergent-resistant membranes named lipid rafts, and occur as monomers or weak homo- or heterodimers like ALG-2. They can serve as a mediator for Ca2+ signaling-related Dictyostehum programmed cell death (PCD).


Pssm-ID: 320060 [Multi-domain]  Cd Length: 163  Bit Score: 36.81  E-value: 7.05e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 187 LQIAFQEFDRDRDGYIGYRELGACMRTLGYM---PTEMELIEISQQISGGKVDFEDFVELMgpkllaetadmIGVRELRD 263
Cdd:cd16185   68 MQNGFEQRDTSRSGRLDANEVHEALAASGFQldpPAFQALFRKFDPDRGGSLGFDDYIELC-----------IFLASARN 136
                         90
                 ....*....|....*
gi 569005821 264 AFREFDTNGDGCISV 278
Cdd:cd16185  137 LFQAFDRQRTGRVTL 151
EFh_PEF_Group_II_CAPN_like cd16182
Penta-EF hand, calcium binding motifs, found in PEF calpain family; The PEF calpain family ...
183-280 7.45e-03

Penta-EF hand, calcium binding motifs, found in PEF calpain family; The PEF calpain family belongs to the second group of penta-EF hand (PEF) proteins. It includes classical (also called conventional or typical) calpain (referring to a calcium-dependent papain-like enzymes, EC 3.4.22.17) large catalytic subunits (CAPN1, 2, 3, 8, 9, 11, 12, 13, 14) and two calpain small subunits (CAPNS1 and CAPNS2), which are largely confined to animals (metazoans). These PEF-containing are nonlysosomal intracellular calcium-activated intracellular cysteine proteases that play important roles in the degradation or functional modulation in a variety of substrates in response to calcium signalling. The classical mu- and m-calpains are heterodimers consisting of homologous but a distinct (large) L-subunit/chain (CAPN1 or CAPN2) and a common (small) S-subunit/chain (CAPNS1 or CAPNS2). These L-subunits (CAPN1 and CAPN2) and S-subunit CAPNS1 are ubiquitously found in all tissues. Other calpains likely consist of an isolated L-subunit/chain alone. Many of them, such as CAPNS2, CAPN3 (in skeletal muscle, or lens), CAPN8 (in stomach), CAPN9 (in digestive tracts), CAPN11 (in testis), CAPN12 (in follicles), are tissue-specific and have specific functions in distinct organs. The L-subunits of similar structure (called CALPA and B) also have been found in Drosophila melanogaster. The S-subunit seems to have a chaperone-like function for proper folding of the L-subunit. The catalytic L-subunits contain a short N-terminal anchor helix, followed by a calpain cysteine protease (CysPc) domain, a C2-domain-like (C2L) domain, and a C-terminal Ca2+-binding penta-EF-hand (PEF) domain. The S-subunits only have the PEF domain following an N-terminal Gly-rich hydrophobic domain. The calpains undergo a rearrangement of the protein backbone upon Ca2+-binding.


Pssm-ID: 320057 [Multi-domain]  Cd Length: 167  Bit Score: 36.43  E-value: 7.45e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 569005821 183 EIEELQIAFQEFDRDRDGYIGYRELGACMRTLGYMPTEMELIEISQQISG--GKVDFEDFVelmgpkllaetADMIGVRE 260
Cdd:cd16182   70 DLKKWQAIFKKFDTDRSGTLSSYELRKALESAGFHLSNKVLQALVLRYADstGRITFEDFV-----------SCLVRLKT 138
                         90       100
                 ....*....|....*....|
gi 569005821 261 LRDAFREFDTNGDGCISVGE 280
Cdd:cd16182  139 AFETFSALDKKNEGVIPLTL 158
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.20
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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