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Conserved domains on  [gi|190194423|ref|NP_001121782|]
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SPARC-like protein 1 isoform 1 precursor [Homo sapiens]

Protein Classification

KAZAL_FS and EFh_SPARC_like domain-containing protein( domain architecture ID 13457661)

protein containing domains PRK08581, KAZAL_FS, and EFh_SPARC_like

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
EFh_SPARC_like cd16231
EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich ...
 515-655 5.27e-61

EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich in cysteine (SPARC) and similar proteins; This family includes secreted protein acidic and rich in cysteine (SPARC), secreted protein, acidic and rich in cysteine-like 1 (SPARCL1), and similar proteins. SPARC is a prototypic collagen-binding matricellular protein that is involved in extracellular matrix (ECM) assembly and fibrosis through binding both fibrillar collagen and basal lamina collagen IV. It regulates the activity of matrix metalloproteinases (MMPs), as well as the growth factor signaling mediated by cell surface receptors including vascular endothelial growth factor (VEGF) receptor, basic fibroblast growth factor (bFGF), and transforming growth factor (TGF) beta1. It also shows survival activity in tumor progression. SPARC contains an N-terminal acidic 52-residue segment followed by a follistatin-like (FS) domain, and an alpha-helical EC domain with 2 unusual calcium-binding EF-hands and the collagen-binding site. SPARCL1 is the closest family member to SPARC. It shares the three primary domains contained within SPARC with an expanded N-terminal domain. SPARCL1 may function as both a tumor suppressor and as a regulator of angiogenesis. It can bind to collagens and be counter-adhesive to wild-type dermal fibroblasts, but do not influence rates of cell proliferation. Moreover, SPARCL1 can influence central nervous system (CNS) development and synaptic rearrangement.


:

Pssm-ID: 320010  Cd Length: 116  Bit Score: 199.11  E-value: 5.27e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423 515 CTDFEVIQFPLRMRDWLKNILMQLYEANSEHAGYLNEkqrnkvkkiyldekrllagdhpidlLLRDFKKNYHMYVYPVHW 594
Cdd:cd16231    1 CLDEELSEFPLRMRDWLKNVMVQLAERDELHEGLTEK-------------------------ELEDFQKNYKMYVYPVHW 55

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 190194423 595 QFSELDQHPMDRVLTHSELAPLRASLVPMEHCITRFFEECDPNKDKHITLKEWGHCFGIKE 655
Cdd:cd16231   56 KFCDLDQHPHDRYLSHHELAPLRAPLVPMEHCTTPFLETCDADNDKLISLKEWGACLGLKE 116
KAZAL_FS super family cl00097
Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit ...
 433-512 4.82e-26

Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit serine proteases, such as, trypsin, chyomotrypsin, avian ovomucoids, and elastases. The inhibitory domain has one reactive site peptide bond, which serves the cognate enzyme as substrate. The reactive site peptide bond is a combining loop which has an identical conformation in all Kazal inhibitors and in all enzyme/inhibitor complexes. These Kazal domains (small hydrophobic core of alpha/beta structure with 3 to 4 disulfide bonds) often occur in tandem arrays. Similar domains are also present in follistatin (FS) and follistatin-like family members, which play an important role in tissue specific regulation. The FS domain consists of an N-terminal beta hairpin (FOLN/EGF-like domain) and a Kazal-like domain and has five disulfide bonds. Although the Kazal-like FS substructure is similar to Kazal proteinase inhibitors, no FS domain has yet been shown to be a proteinase inhibitor. Follistatin-like family members include SPARC, also known as, BM-40 or osteonectin, the Gallus gallus Flik protein, as well as, agrin which has a long array of FS domains. The kazal-type inhibitor domain has also been detected in an extracellular loop region of solute carrier 21 (SLC21) family members (organic anion transporters) , which may regulate the specificity of anion uptake. The distant homolog, Ascidian trypsin inhibitor, is included in this CD.


The actual alignment was detected with superfamily member cd01328:

Pssm-ID: 412159 [Multi-domain]  Cd Length: 86  Bit Score: 102.17  E-value: 4.82e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423 433 CMSFQCKRGHICKADQQGKPHCVCQDPvtCPP-TKPLDQVCGTDNQTYASSCHLFATKCRLEGTKKGH------QLQLDY 505
Cdd:cd01328    2 CENHHCGAGKVCEVDDENTPKCVCIDP--CPEeVDDRRKVCTNDNETFDSDCELYRTRCLCKGGKKGCrgpkyqHLHLDY 79


                 ....*..
gi 190194423 506 FGACKSI 512
Cdd:cd01328   80 YGECKEI 86
PRK08581 super family cl35718
amidase domain-containing protein;
1-297 1.08e-04

amidase domain-containing protein;


The actual alignment was detected with superfamily member PRK08581:

Pssm-ID: 236304 [Multi-domain]  Cd Length: 619  Bit Score: 45.55  E-value: 1.08e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423   1 MKTGLFFLCLLGTAAAIPTnarLLSDHSKPTAETVAPDNTAIPSLRAEAEENEKETAVSTEDDSHHKAEKSSVLKSKEES 80
Cdd:PRK08581   1 MKKNKILIYLLSTTLVLPT---LTSPTAYADDPQKDSTAKTTSHDSKKSNDDETSKDTSSKDTDKADNNNTSNQDNNDKK 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423  81 HEQSAEQGKSSSQelgLKDQEDSDGHLSVNLEYAPTEGTLDiKEDMSEPQEKKLSENtdflapgvSSFTDSNQQESITKR 160
Cdd:PRK08581  78 FSTIDSSTSDSNN---IIDFIYKNLPQTNINQLLTKNKYDD-NYSLTTLIQNLFNLN--------SDISDYEQPRNSEKS 145

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423 161 EENQEQPRNYSHHQLNRSSKHSQGLRDQGNQEQDPNISNGEEEEEKEPGEVGTHNDNQERKTELPREHANSKQEEDNTQS 240
Cdd:PRK08581 146 TNDSNKNSDSSIKNDTDTQSSKQDKADNQKAPSSNNTKPSTSNKQPNSPKPTQPNQSNSQPASDDTANQKSSSKDNQSMS 225

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 190194423 241 DDILEES-DQPTQVSKMQEDEFD-QGNQEQEDNSNAEMEEENASNVNKHiQETEWQSQE 297
Cdd:PRK08581 226 DSALDSIlDQYSEDAKKTQKDYAsQSKKDKTETSNTKNPQLPTQDELKH-KSKPAQSFE 283
 
Name Accession Description Interval E-value
EFh_SPARC_like cd16231
EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich ...
 515-655 5.27e-61

EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich in cysteine (SPARC) and similar proteins; This family includes secreted protein acidic and rich in cysteine (SPARC), secreted protein, acidic and rich in cysteine-like 1 (SPARCL1), and similar proteins. SPARC is a prototypic collagen-binding matricellular protein that is involved in extracellular matrix (ECM) assembly and fibrosis through binding both fibrillar collagen and basal lamina collagen IV. It regulates the activity of matrix metalloproteinases (MMPs), as well as the growth factor signaling mediated by cell surface receptors including vascular endothelial growth factor (VEGF) receptor, basic fibroblast growth factor (bFGF), and transforming growth factor (TGF) beta1. It also shows survival activity in tumor progression. SPARC contains an N-terminal acidic 52-residue segment followed by a follistatin-like (FS) domain, and an alpha-helical EC domain with 2 unusual calcium-binding EF-hands and the collagen-binding site. SPARCL1 is the closest family member to SPARC. It shares the three primary domains contained within SPARC with an expanded N-terminal domain. SPARCL1 may function as both a tumor suppressor and as a regulator of angiogenesis. It can bind to collagens and be counter-adhesive to wild-type dermal fibroblasts, but do not influence rates of cell proliferation. Moreover, SPARCL1 can influence central nervous system (CNS) development and synaptic rearrangement.


Pssm-ID: 320010  Cd Length: 116  Bit Score: 199.11  E-value: 5.27e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423 515 CTDFEVIQFPLRMRDWLKNILMQLYEANSEHAGYLNEkqrnkvkkiyldekrllagdhpidlLLRDFKKNYHMYVYPVHW 594
Cdd:cd16231    1 CLDEELSEFPLRMRDWLKNVMVQLAERDELHEGLTEK-------------------------ELEDFQKNYKMYVYPVHW 55

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 190194423 595 QFSELDQHPMDRVLTHSELAPLRASLVPMEHCITRFFEECDPNKDKHITLKEWGHCFGIKE 655
Cdd:cd16231   56 KFCDLDQHPHDRYLSHHELAPLRAPLVPMEHCTTPFLETCDADNDKLISLKEWGACLGLKE 116
SPARC_Ca_bdg pfam10591
Secreted protein acidic and rich in cysteine Ca binding region; The SPARC_Ca_bdg domain of ...
 513-649 2.33e-45

Secreted protein acidic and rich in cysteine Ca binding region; The SPARC_Ca_bdg domain of Secreted Protein Acidic and Rich in Cysteine is responsible for the anti-spreading activity of human urothelial cells. It is rich in alpha-helices. This extracellular calcium-binding domain contains two EF-hands that each coordinates one Ca2+ ion, forming a helix-loop-helix structure that not only drives the conformation of the protein but is also necessary for biological activity. The anti-spreading activity was dependent on the coordination of Ca2+ by a Glu residue at the Z position of EF-hand 2.


Pssm-ID: 463162  Cd Length: 111  Bit Score: 156.73  E-value: 2.33e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423  513 PTCTDFEVIQFPLRMRDWLKNILMQLYEANSEHagylnekqrnkvkkiyldekrllagDHPIDLLLRDFKKNYHMYVYPV 592
Cdd:pfam10591   1 PCCTDEELAEFPRRMRDWLKLLLEALRNRRERK-------------------------DHSSTLEKRDESLLYPCCKDPL 55

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 190194423  593 HWQFSELDQHpMDRVLTHSELAPLRASLVPMEHCITRFFEECDPNKDKHITLKEWGH 649
Cdd:pfam10591  56 GWMFKRLDTN-DDLLLDHEELAPIRAPLKPEEHCIKPFFESCDANKDKLISLEEWCC 111
FSL_SPARC cd01328
Follistatin-like SPARC (secreted protein, acidic, and rich in cysteines) domain; SPARC/BM-40 ...
 433-512 4.82e-26

Follistatin-like SPARC (secreted protein, acidic, and rich in cysteines) domain; SPARC/BM-40/osteonectin is a multifunctional glycoprotein which modulates cellular interaction with the extracellular matrix by its binding to structural matrix proteins such as collagen and vitronectin. The protein it composed of an N-terminal acidic region, a follistatin (FS) domain and an EF-hand calcium binding domain. The FS domain consists of an N-terminal beta hairpin (FOLN/EGF-like domain) and a small hydrophobic core of alpha/beta structure (Kazal domain) and has five disulfide bonds and a conserved N-glycosylation site. The FSL_SPARC domain is a member of the superfamily of kazal-like proteinase inhibitors and follistatin-like proteins.


Pssm-ID: 238649 [Multi-domain]  Cd Length: 86  Bit Score: 102.17  E-value: 4.82e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423 433 CMSFQCKRGHICKADQQGKPHCVCQDPvtCPP-TKPLDQVCGTDNQTYASSCHLFATKCRLEGTKKGH------QLQLDY 505
Cdd:cd01328    2 CENHHCGAGKVCEVDDENTPKCVCIDP--CPEeVDDRRKVCTNDNETFDSDCELYRTRCLCKGGKKGCrgpkyqHLHLDY 79


                 ....*..
gi 190194423 506 FGACKSI 512
Cdd:cd01328   80 YGECKEI 86
Kazal_1 pfam00050
Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. ...
 456-509 3.66e-11

Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. However, kazal-like domains are also seen in the extracellular part of agrins, which are not known to be protease inhibitors. Kazal domains often occur in tandem arrays. Small alpha+beta fold containing three disulphides. Alignment also includes a single domain from transporters in the OATP/PGT family.


Pssm-ID: 395004  Cd Length: 49  Bit Score: 58.45  E-value: 3.66e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 190194423  456 CQDPVTCPPTKPLDQVCGTDNQTYASSCHLfatkCRLEGtKKGHQLQLDYFGAC 509
Cdd:pfam00050   1 CSDYPSGACPRIYDPVCGTDGKTYSNECLF----CAENG-KRGTNLHKVHDGEC 49
KAZAL smart00280
Kazal type serine protease inhibitors; Kazal type serine protease inhibitors and ...
 455-509 4.94e-10

Kazal type serine protease inhibitors; Kazal type serine protease inhibitors and follistatin-like domains.


Pssm-ID: 197624  Cd Length: 46  Bit Score: 54.99  E-value: 4.94e-10
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 190194423   455 VCqdPVTCPptKPLDQVCGTDNQTYASSCHLFATKCrlegtKKGHQLQLDYFGAC 509
Cdd:smart00280   1 DC--PEACP--REYDPVCGSDGVTYSNECHLCKAAC-----ESGKSIEVKHDGPC 46
PRK08581 PRK08581
amidase domain-containing protein;
1-297 1.08e-04

amidase domain-containing protein;


Pssm-ID: 236304 [Multi-domain]  Cd Length: 619  Bit Score: 45.55  E-value: 1.08e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423   1 MKTGLFFLCLLGTAAAIPTnarLLSDHSKPTAETVAPDNTAIPSLRAEAEENEKETAVSTEDDSHHKAEKSSVLKSKEES 80
Cdd:PRK08581   1 MKKNKILIYLLSTTLVLPT---LTSPTAYADDPQKDSTAKTTSHDSKKSNDDETSKDTSSKDTDKADNNNTSNQDNNDKK 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423  81 HEQSAEQGKSSSQelgLKDQEDSDGHLSVNLEYAPTEGTLDiKEDMSEPQEKKLSENtdflapgvSSFTDSNQQESITKR 160
Cdd:PRK08581  78 FSTIDSSTSDSNN---IIDFIYKNLPQTNINQLLTKNKYDD-NYSLTTLIQNLFNLN--------SDISDYEQPRNSEKS 145

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423 161 EENQEQPRNYSHHQLNRSSKHSQGLRDQGNQEQDPNISNGEEEEEKEPGEVGTHNDNQERKTELPREHANSKQEEDNTQS 240
Cdd:PRK08581 146 TNDSNKNSDSSIKNDTDTQSSKQDKADNQKAPSSNNTKPSTSNKQPNSPKPTQPNQSNSQPASDDTANQKSSSKDNQSMS 225

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 190194423 241 DDILEES-DQPTQVSKMQEDEFD-QGNQEQEDNSNAEMEEENASNVNKHiQETEWQSQE 297
Cdd:PRK08581 226 DSALDSIlDQYSEDAKKTQKDYAsQSKKDKTETSNTKNPQLPTQDELKH-KSKPAQSFE 283
Agg_substance NF033875
LPXTG-anchored aggregation substance; Aggregation substances, as described in Enterococcus, ...
 5-309 3.32e-04

LPXTG-anchored aggregation substance; Aggregation substances, as described in Enterococcus, are LPXTG-anchored large surface proteins that contribute to virulence. Several closely related paralogs may be found in a single strain.


Pssm-ID: 411439 [Multi-domain]  Cd Length: 1306  Bit Score: 43.93  E-value: 3.32e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423    5 LFFLCLLGTAAAIPTNARLLSDHSKPTAETVAPDNtaiPSLRAEAEEneKETAVSTE----DDSHHKAEKSSVLKSKEES 80
Cdd:NF033875   25 ILFLGVLGVVGLATDNVQAAELDTQPGTTTVQPDN---PDPQSGSET--PKTAVSEEatvqKDTTSQPTKVEEVASEKNG 99

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423   81 HEQS---------AEQ----GKSSSQELGLKDQEDSDGHLSVNLEYAPTEGtlDIKEDMSEPQEkklsentdFLAPGVSS 147
Cdd:NF033875  100 AEQSsatpndttnAQQptvgAEKSAQEQPVVSPETTNEPLGQPTEVAPAEN--EANKSTSIPKE--------FETPDVDK 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423  148 FTDSNQQE-SITKREENQEQPRNYSHHQLNRSSKHSqglrDQGNQEQDPNISNGEEEEEKEPGEVGTHN-----DNQERK 221
Cdd:NF033875  170 AVDEAKKDpNITVVEKPAEDLGNVSSKDLAAKEKEV----DQLQKEQAKKIAQQAAELKAKNEKIAKENaeiaaKNKAEK 245

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423  222 TELPRE------HANSKQEEDNTQSDDILEESDQPTQVSK---------MQEDEFDQGNQEQEDNSNAEMEEENASNVNK 286
Cdd:NF033875  246 ERYEKEvaeynkHKNENGYVNEAISKNLVFDQSVVTKDTKissikggkfIKATDFNKVNAGDSKDIFTKLSKDMGGKATG 325

                         330       340
                  ....*....|....*....|....
gi 190194423  287 HIQETEWQSQE-GKTGLEAISNHK 309
Cdd:NF033875  326 NFQNSFVKEANlGSNGGYAVLLEK 349
 
Name Accession Description Interval E-value
EFh_SPARC_like cd16231
EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich ...
 515-655 5.27e-61

EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich in cysteine (SPARC) and similar proteins; This family includes secreted protein acidic and rich in cysteine (SPARC), secreted protein, acidic and rich in cysteine-like 1 (SPARCL1), and similar proteins. SPARC is a prototypic collagen-binding matricellular protein that is involved in extracellular matrix (ECM) assembly and fibrosis through binding both fibrillar collagen and basal lamina collagen IV. It regulates the activity of matrix metalloproteinases (MMPs), as well as the growth factor signaling mediated by cell surface receptors including vascular endothelial growth factor (VEGF) receptor, basic fibroblast growth factor (bFGF), and transforming growth factor (TGF) beta1. It also shows survival activity in tumor progression. SPARC contains an N-terminal acidic 52-residue segment followed by a follistatin-like (FS) domain, and an alpha-helical EC domain with 2 unusual calcium-binding EF-hands and the collagen-binding site. SPARCL1 is the closest family member to SPARC. It shares the three primary domains contained within SPARC with an expanded N-terminal domain. SPARCL1 may function as both a tumor suppressor and as a regulator of angiogenesis. It can bind to collagens and be counter-adhesive to wild-type dermal fibroblasts, but do not influence rates of cell proliferation. Moreover, SPARCL1 can influence central nervous system (CNS) development and synaptic rearrangement.


Pssm-ID: 320010  Cd Length: 116  Bit Score: 199.11  E-value: 5.27e-61
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423 515 CTDFEVIQFPLRMRDWLKNILMQLYEANSEHAGYLNEkqrnkvkkiyldekrllagdhpidlLLRDFKKNYHMYVYPVHW 594
Cdd:cd16231    1 CLDEELSEFPLRMRDWLKNVMVQLAERDELHEGLTEK-------------------------ELEDFQKNYKMYVYPVHW 55

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 190194423 595 QFSELDQHPMDRVLTHSELAPLRASLVPMEHCITRFFEECDPNKDKHITLKEWGHCFGIKE 655
Cdd:cd16231   56 KFCDLDQHPHDRYLSHHELAPLRAPLVPMEHCTTPFLETCDADNDKLISLKEWGACLGLKE 116
EFh_SPARC_SPARCL1 cd16236
EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein, acidic and rich ...
 515-655 1.12e-60

EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein, acidic and rich in cysteine-like 1 (SPARCL1); SPARCL1, also termed SPARC-like protein 1, or high endothelial venule protein (Hevin), or MAST 9, or SC-1, or RAGS-1, or QR1, or ECM 2, is a diversely expressed and developmentally regulated extracellular matrix glycoprotein involved in tissue repair and remodeling via interaction with the surrounding extracellular matrix (ECM) proteins. It plays a pivotal role in the corneal wound healing. SPARCL1 may function as both a tumor suppressor and as a regulator of angiogenesis. It regulates cell migration/invasion and suppresses metastasis in many cancers, including prostate cancer, colorectal cancer, gastric cancer, and breast cancer. It can bind to collagens and be counter-adhesive to wild-type dermal fibroblasts, but do not influence rates of cell proliferation. Moreover, SPARCL1 contributes to neural development and participates in remodeling events associated with neuronal degeneration following neural injury. It can influence central nervous system (CNS) development and synaptic rearrangement. SPARCL1 is the closest family member to secreted protein acidic and rich in cysteine (SPARC), but does not compensate for the absence of SPARC in the CNS. SPARC contains an N-terminal acidic 52-residue segment followed by a follistatin-like (FS) domain, and an alpha-helical EC domain with 2 unusual calcium-binding EF-hands and the collagen-binding site. SPARCL1 shares the three primary domains contained within SPARC with an expanded N-terminal domain.


Pssm-ID: 320015  Cd Length: 93  Bit Score: 197.52  E-value: 1.12e-60
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423 515 CTDFEVIQFPLRMRDWLKNILMQLYeansehagylnekqrnkvkkiyldekrllagdhpidlllrdfkknyhmYVYPVHW 594
Cdd:cd16236    1 CTDSEVVQFPLRMRDWLKNILMQLY------------------------------------------------YIYPVHW 32

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 190194423 595 QFSELDQHPMDRVLTHSELAPLRASLVPMEHCITRFFEECDPNKDKHITLKEWGHCFGIKE 655
Cdd:cd16236   33 QFAQLDQHPSDRFLTHSELAPLRASLVPMEHCITRFFQECDADKDKLITLKEWCHCFGIKE 93
SPARC_Ca_bdg pfam10591
Secreted protein acidic and rich in cysteine Ca binding region; The SPARC_Ca_bdg domain of ...
 513-649 2.33e-45

Secreted protein acidic and rich in cysteine Ca binding region; The SPARC_Ca_bdg domain of Secreted Protein Acidic and Rich in Cysteine is responsible for the anti-spreading activity of human urothelial cells. It is rich in alpha-helices. This extracellular calcium-binding domain contains two EF-hands that each coordinates one Ca2+ ion, forming a helix-loop-helix structure that not only drives the conformation of the protein but is also necessary for biological activity. The anti-spreading activity was dependent on the coordination of Ca2+ by a Glu residue at the Z position of EF-hand 2.


Pssm-ID: 463162  Cd Length: 111  Bit Score: 156.73  E-value: 2.33e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423  513 PTCTDFEVIQFPLRMRDWLKNILMQLYEANSEHagylnekqrnkvkkiyldekrllagDHPIDLLLRDFKKNYHMYVYPV 592
Cdd:pfam10591   1 PCCTDEELAEFPRRMRDWLKLLLEALRNRRERK-------------------------DHSSTLEKRDESLLYPCCKDPL 55

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 190194423  593 HWQFSELDQHpMDRVLTHSELAPLRASLVPMEHCITRFFEECDPNKDKHITLKEWGH 649
Cdd:pfam10591  56 GWMFKRLDTN-DDLLLDHEELAPIRAPLKPEEHCIKPFFESCDANKDKLISLEEWCC 111
EFh_SPARC_SPARC cd16235
EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich ...
 515-655 4.04e-42

EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich in cysteine (SPARC); SPARC, also termed basement-membrane protein 40 (BM-40), or osteonectin (ON), is a prototypic collagen-binding matricellular protein that is essential for embryo development in invertebrates and highly expressed in bone. It participates in normal tissue remodeling as it regulates the deposition of extracellular matrix, as well as in neoplastic transformation. It is involved in extracellular matrix (ECM) assembly and fibrosis through binding both fibrillar collagen and basal lamina collagen IV. It regulates the activity of matrix metalloproteinases (MMPs), as well as the growth factor signaling mediated by cell surface receptors including vascular endothelial growth factor (VEGF) receptor, basic fibroblast growth factor (bFGF), and transforming growth factor (TGF) beta1. SPARC shows survival activity in tumor progression. It plays a role in metastatic process to the lung during melanoma progression. It can suppress prostate cancer cell growth and survival. Moreover, SPARC is a bone- associated protein that has a major role in bone development and mineralisationis. It is involved in the initiation and progression of vascular calcification and upregulated by adiponectin. Furthermore, SPARC may be one of the molecules that govern the uptake and delivery of proteins from blood to the cerebrospinal fluid (CSF) during brain development. SPARC contains an N-terminal acidic 52-residue segment followed by a follistatin-like (FS) domain, and an alpha-helical EC domain with 2 unusual calcium-binding EF-hands and the collagen-binding site. Platelet-derived growth factor (PDGF) also interacts with its EC domain, but in a calcium-independent manner, whereas collagen binding is calcium-dependent.


Pssm-ID: 320014  Cd Length: 96  Bit Score: 147.46  E-value: 4.04e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423 515 CTDFEVIQFPLRMRDWLKNILMQLYEansehagylnekqrnkvkkiyldekrllagdhpidlllRDfkknyhmYVYPVHW 594
Cdd:cd16235    1 CLDSELTEFPLRMRDWLKNVLVTLYE--------------------------------------RD-------YIFPVHW 35

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 190194423 595 QFSELDQHPMDRVLTHSELAPLRASLVPMEHCITRFFEECDPNKDKHITLKEWGHCFGIKE 655
Cdd:cd16235   36 QFGQLDQHPIDGYLSHTELAPLRAPLIPMEHCTTRFFETCDLDNDKYIALDEWAGCFGIKQ 96
FSL_SPARC cd01328
Follistatin-like SPARC (secreted protein, acidic, and rich in cysteines) domain; SPARC/BM-40 ...
 433-512 4.82e-26

Follistatin-like SPARC (secreted protein, acidic, and rich in cysteines) domain; SPARC/BM-40/osteonectin is a multifunctional glycoprotein which modulates cellular interaction with the extracellular matrix by its binding to structural matrix proteins such as collagen and vitronectin. The protein it composed of an N-terminal acidic region, a follistatin (FS) domain and an EF-hand calcium binding domain. The FS domain consists of an N-terminal beta hairpin (FOLN/EGF-like domain) and a small hydrophobic core of alpha/beta structure (Kazal domain) and has five disulfide bonds and a conserved N-glycosylation site. The FSL_SPARC domain is a member of the superfamily of kazal-like proteinase inhibitors and follistatin-like proteins.


Pssm-ID: 238649 [Multi-domain]  Cd Length: 86  Bit Score: 102.17  E-value: 4.82e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423 433 CMSFQCKRGHICKADQQGKPHCVCQDPvtCPP-TKPLDQVCGTDNQTYASSCHLFATKCRLEGTKKGH------QLQLDY 505
Cdd:cd01328    2 CENHHCGAGKVCEVDDENTPKCVCIDP--CPEeVDDRRKVCTNDNETFDSDCELYRTRCLCKGGKKGCrgpkyqHLHLDY 79


                 ....*..
gi 190194423 506 FGACKSI 512
Cdd:cd01328   80 YGECKEI 86
EFh_SPARC_EC cd00252
EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich ...
 515-653 9.41e-25

EF-hand, extracellular calcium-binding (EC) motif, found in secreted protein acidic and rich in cysteine (SPARC)-like proteins; The SPARC protein family represents a diverse group of proteins that share a follistatin-like (FS) domain and an extracellular calcium-binding (EC) domain with two EF-hand motifs. It includes SPARC (for secreted protein acidic and rich in cysteine, also termed osteonectin/ON, or basement-membrane protein 40/BM-40), SPARC-like protein 1 (for secreted protein, acidic and rich in cysteines-like 1/ SPARCL1, also termed high endothelial venule protein/Hevi, or MAST 9, or SC-1, or RAGS-1, or QR1, or ECM 2), testicans 1, 2, and 3 (also termed SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycans, or SPOCK), secreted modular calcium-binding protein SMOC-1 (also termed SPARC-related modular calcium-binding protein 1) and SMOC-2 (also termed SPARC-related modular calcium-binding protein 2, or smooth muscle-associated protein 2/SMAP-2), follistatin-related protein 1 (FRP-1, also termed follistatin-like protein 1/fstl-1, TSC-36/Flik, TGF-beta inducible protein). The SPARC proteins have been implicated in modulating cell interaction with the extracellular milieu, including regulation of extracellular matrix assembly and deposition, counter-adhesion, effects on extracellular protease activity, and modulation of growth factor/cytokine signaling pathways, as well as in development and disease.


Pssm-ID: 320009  Cd Length: 107  Bit Score: 98.98  E-value: 9.41e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423 515 CTDFEVIQFPLRMRDWLKNILMQLYEANSEHAGylnekqrnkvkkiyldekrllagdhpidlllRDFKKNYHMYVYPVHW 594
Cdd:cd00252    1 CPGSELMQFPDRLLDWLLLLKEQDENRSYDNNK-------------------------------RGHDLSGTMRKEIAQW 49

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 190194423 595 QFSELDQhPMDRVLTHSELAPLRASLVPMEHCITRFFEECDPNKDKHITLKEWGHCFGI 653
Cdd:cd00252   50 EFDNLDN-NKDGKLDKRELAPFRAPLMPLEHCARGFFESCDLNKDKKISLQEWLGCFGV 107
EFh_SPARC_TICN cd16232
EF-hand, extracellular calcium-binding (EC) motif, found in testicans; Testicans are nervous ...
 515-651 1.16e-11

EF-hand, extracellular calcium-binding (EC) motif, found in testicans; Testicans are nervous system-expressed proteoglycans that play important roles in the regulation of protease activity, as well as in the determination of age at menarche. Testican-1 (TICN1, also termed protein SPOCK) is a secreted chimeric proteoglycan that is highly expressed in brain and carries both chondroitin and heparan sulfate glycosaminoglycan side chains. It has been implicated in autoimmune disease. It also acts as a regulator of bone morphogenetic protein (BMP) signaling and show critical functions in the nervous system. Testican-2 (TICN2, also termed protein SPOCK2) is an extracellular heparan sulphate proteoglycan highly expressed in brain. It may play regulatory roles in the development of the central nervous system. It also participates in diverse steps of neurogenesis. TICN1, but not TICN2, inhibits cathepsin L. TICN1 also inhibits attachment and neurite outgrowth in cultures of N2A neuroblastoma cells, While TICN2 is able to inhibit neurite outgrowth from primary cerebellar cells. Testicans contain an N-terminal signal peptide, a testican-specific domain followed by a follistatin-like (FS) domain, an extracellular calcium-binding (EC) domain including a pair of EF hands, a thyroglobulin-like domain (TY), and a C-terminal region with two putative glycosaminoglycan attachment sites. The substitution of a ligating Asp residue by Tyr orTyr in the +Y position of EF hand 2 in testican-2 could prevent Ca2+ binding to this site and also cause EF-hand 1 to bind one Ca2+ with low affinity. The substitution of a ligating Asp residue by Phe or Tyr in the +Y position of EF-hand 2 in testicans could prevent Ca2+ binding to this site and also cause EF-hand 1 to bind one Ca2+ ion with low affinity.


Pssm-ID: 320011  Cd Length: 108  Bit Score: 61.62  E-value: 1.16e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423 515 CTDFEVIQFPLRMRDWLKNIlmqlyeanseHAgylNEKQRNKVKKiyldEKRLLAGDHPIdllLRDfkknyhmyvyPVHW 594
Cdd:cd16232    1 CTESELSEMGDRLLDWFSVL----------HE---QSNKAKKTSS----SKRFDKSHLPE---CKP----------SVGW 50

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 190194423 595 QFSELDQHpMDRVLTHSELAPLraSLVPMEHCITRFFEECDPNKDKHITLKEWGHCF 651
Cdd:cd16232   51 MFNQLDTN-NDLHLSQSELYDL--ELDKYEPCIKPFLDSCDRNKDGKISSDEWCDCF 104
Kazal_1 pfam00050
Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. ...
 456-509 3.66e-11

Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. However, kazal-like domains are also seen in the extracellular part of agrins, which are not known to be protease inhibitors. Kazal domains often occur in tandem arrays. Small alpha+beta fold containing three disulphides. Alignment also includes a single domain from transporters in the OATP/PGT family.


Pssm-ID: 395004  Cd Length: 49  Bit Score: 58.45  E-value: 3.66e-11
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 190194423  456 CQDPVTCPPTKPLDQVCGTDNQTYASSCHLfatkCRLEGtKKGHQLQLDYFGAC 509
Cdd:pfam00050   1 CSDYPSGACPRIYDPVCGTDGKTYSNECLF----CAENG-KRGTNLHKVHDGEC 49
Kazal_2 pfam07648
Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. ...
 461-509 2.27e-10

Kazal-type serine protease inhibitor domain; Usually indicative of serine protease inhibitors. However, kazal-like domains are also seen in the extracellular part of agrins, which are not known to be protease inhibitors. Kazal domains often occur in tandem arrays. Small alpha+beta fold containing three disulphides.


Pssm-ID: 400135  Cd Length: 50  Bit Score: 56.35  E-value: 2.27e-10
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 190194423  461 TCPPTKpLDQVCGTDNQTYASSCHLFATKCRLEGTKKGHqlQLDYFGAC 509
Cdd:pfam07648   5 QCPKTE-YEPVCGSDGVTYPSPCALCAAGCKLGKEVKEE--KVKYDGSC 50
EFh_SPARC_SMOC cd16234
EF-hand, extracellular calcium-binding (EC) motif, found in secreted modular calcium-binding ...
 592-653 2.64e-10

EF-hand, extracellular calcium-binding (EC) motif, found in secreted modular calcium-binding protein SMOC-1, SMOC-2, and similar proteins; SMOC proteins corresponds to a group matricellular proteins that are involved in direct or indirect modulation of growth factor signaling pathways and play diverse roles in physiological processes involving extensive tissue remodeling, migration, proliferation, and angiogenesis. They may mediate intercellular signaling and cell type-specific differentiation during gonad and reproductive tract development. SMOC-1 is localized in basement membranes. Its mutations have been found to be associated with individuals with Warrdenburg Anopthalmia Syndrome. SMOC-2 is ubiquitously expressed and is involved in angiogenesis and the regulation of cell cycle progression. It enhances the angiogenic effect of basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF). It has also been implicated in generalized vitiligo. SMOC proteins consist of a follistatin-like (FS) domain, two thyroglobulin-like (TY) domains, a novel domain conserved only in SMOC proteins, and an extracellular calcium-binding (EC) domain with two EF-hand calcium-binding motifs.


Pssm-ID: 320013  Cd Length: 104  Bit Score: 57.67  E-value: 2.64e-10
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 190194423 592 VHWQFSELDQHPmDRVLTHSELAPLRA---SLVPMEHCITRFFEECDPNKDKHITLKEWGHCFGI 653
Cdd:cd16234   41 LDWKFSQLDKNK-NGVLERKEWKPFKRllkKAVKPKKCARKFPKYCDVNKDKKISLTEWLNCLGV 104
KAZAL smart00280
Kazal type serine protease inhibitors; Kazal type serine protease inhibitors and ...
 455-509 4.94e-10

Kazal type serine protease inhibitors; Kazal type serine protease inhibitors and follistatin-like domains.


Pssm-ID: 197624  Cd Length: 46  Bit Score: 54.99  E-value: 4.94e-10
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 190194423   455 VCqdPVTCPptKPLDQVCGTDNQTYASSCHLFATKCrlegtKKGHQLQLDYFGAC 509
Cdd:smart00280   1 DC--PEACP--REYDPVCGSDGVTYSNECHLCKAAC-----ESGKSIEVKHDGPC 46
FOLN pfam09289
Follistatin/Osteonectin-like EGF domain; Members of this family are predominantly found in ...
 433-454 1.77e-08

Follistatin/Osteonectin-like EGF domain; Members of this family are predominantly found in osteonectin and follistatin and adopt an EGF-like fold.


Pssm-ID: 462743  Cd Length: 22  Bit Score: 50.16  E-value: 1.77e-08
                          10        20
                  ....*....|....*....|..
gi 190194423  433 CMSFQCKRGHICKADQQGKPHC 454
Cdd:pfam09289   1 CENFQCKRGKVCKVDKEGKPHC 22
EFh_SPARC_TICN3 cd16239
EF-hand, extracellular calcium-binding (EC) motif, found in testican-3 (TICN3); TICN3, also ...
 515-651 4.30e-08

EF-hand, extracellular calcium-binding (EC) motif, found in testican-3 (TICN3); TICN3, also termed SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycan 3 (Spock3), is a brain-specific heparan sulfate proteoglycan that shows a widespread distribution within the extracellular matrix of the brain. It plays an important role in the formation or maintenance of major neuronal structures in the brain. It also functions as a novel regulator to reduce the activity of matrix metalloproteinase (MMP) in adult T-cell leukemia (ATL). It suppresses membrane-type 1 MMP-mediated MMP-2 activation and tumor invasion. Moreover, TICN3 corresponding gene SPOCK3 acts as a risk gene for adult attention-deficit/hyperactivity disorder (ADHD) and personality disorders. TICN3 contains an N-terminal signal peptide, a testican-specific domain followed by the follistatin-like (FS) and extracellular calcium-binding (EC) domains characteristic of the BM-40 family. Towards the C-terminus they contain a thyroglobulin-like domain (TY) and a novel sequence (domain V), which includes two potential glycosaminoglycan attachment sites. The substitution of a ligating Asp residue by Tyr295 in the +Y position of EF-hand 2 in testican-3 could prevent Ca2+ binding to this site and also cause EF-hand 1 to bind one Ca2+ ion with low affinity.


Pssm-ID: 320018  Cd Length: 113  Bit Score: 51.94  E-value: 4.30e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423 515 CTDFEVIQFPLRMRDWLKnilmQLYEANSEhagylnekqrNKVKKIYLDEKRLLAgDHPIDLLLRDfkknyhmyvyPVHW 594
Cdd:cd16239    1 CSDLEFREVANRLRDWFK----ALHESGSQ----------NKKTKIVRRPERSRF-DTSILPICKD----------SLGW 55

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*..
gi 190194423 595 QFSELDQHpMDRVLTHSELAPLraSLVPMEHCITRFFEECDPNKDKHITLKEWGHCF 651
Cdd:cd16239   56 MFNRLDTN-YDLLLDQSELGSI--YLDKNEQCTKAFFNSCDTYKDSLISNNEWCYCF 109
KAZAL_FS cd00104
Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit ...
 462-509 6.88e-08

Kazal type serine protease inhibitors and follistatin-like domains. Kazal inhibitors inhibit serine proteases, such as, trypsin, chyomotrypsin, avian ovomucoids, and elastases. The inhibitory domain has one reactive site peptide bond, which serves the cognate enzyme as substrate. The reactive site peptide bond is a combining loop which has an identical conformation in all Kazal inhibitors and in all enzyme/inhibitor complexes. These Kazal domains (small hydrophobic core of alpha/beta structure with 3 to 4 disulfide bonds) often occur in tandem arrays. Similar domains are also present in follistatin (FS) and follistatin-like family members, which play an important role in tissue specific regulation. The FS domain consists of an N-terminal beta hairpin (FOLN/EGF-like domain) and a Kazal-like domain and has five disulfide bonds. Although the Kazal-like FS substructure is similar to Kazal proteinase inhibitors, no FS domain has yet been shown to be a proteinase inhibitor. Follistatin-like family members include SPARC, also known as, BM-40 or osteonectin, the Gallus gallus Flik protein, as well as, agrin which has a long array of FS domains. The kazal-type inhibitor domain has also been detected in an extracellular loop region of solute carrier 21 (SLC21) family members (organic anion transporters) , which may regulate the specificity of anion uptake. The distant homolog, Ascidian trypsin inhibitor, is included in this CD.


Pssm-ID: 238052 [Multi-domain]  Cd Length: 41  Bit Score: 48.81  E-value: 6.88e-08
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*...
gi 190194423 462 CPPTkpLDQVCGTDNQTYASSCHLFATKCRlegtkKGHQLQLDYFGAC 509
Cdd:cd00104    1 CPKE--YDPVCGSDGKTYSNECHLGCAACR-----SGRSITVAHNGPC 41
EFh_SPARC_SMOC1 cd16240
EF-hand, extracellular calcium-binding (EC) motif, found in secreted modular calcium-binding ...
 592-655 4.11e-06

EF-hand, extracellular calcium-binding (EC) motif, found in secreted modular calcium-binding protein 1 (SMOC-1); SMOC-1, also termed SPARC-related modular calcium-binding protein 1, or smooth muscle-associated protein 1 (SMAP-1), is an Arf6 GTPase-activating protein (GAP) that directly interacts with clathrin and regulates the clathrin-dependent endocytosis of transferrin receptors from the plasma membrane. It is predominantly localized in basement membranes. SMOC-1 acts as a regulator of osteoblast differentiation and is involved in inhibition of transforming growth factor-beta (TGF-beta) signaling through production of nitric oxide. It also plays an essential role in ocular and limb development and functions as a regulator of bone morphogenic protein (BMP) signaling. It interacts with a matricellular protein, tenascin C in addition to the serum proteins, fibulin-1 and C-reactive protein, but not collagens. Two point mutations in the SMOC1 gene may cause Waardenburg Anophtalmia Syndrome. Moreover, SMOC-1 is involved in direct or indirect modulation of growth factor signaling pathways and plays a role in physiological processes involving extensive tissue remodeling. SMOC-1 contains a follistatin-like (FS) domain, two thyroglobulin-like (TY) domains, a novel domain, which is found only in the homologous SMOC-2, and an extracellular calcium-binding (EC) domain with two EF-hand calcium-binding motifs.


Pssm-ID: 320019  Cd Length: 115  Bit Score: 46.18  E-value: 4.11e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 190194423 592 VHWQFSELDQHPMDRVlTHSELAPLRASL---VPMEHCITRFFEECDPNKDKHITLKEWGHCFGIKE 655
Cdd:cd16240   50 VHWYFSQLDNNSSNDI-NKKELKPFKRYVkkkAKPKKCARRFTDYCDLNKDKSISLQELKGCLGVSK 115
EFh_SPARC_SMOC2 cd16241
EF-hand, extracellular calcium-binding (EC) motif, found in secreted modular calcium-binding ...
 592-653 4.98e-06

EF-hand, extracellular calcium-binding (EC) motif, found in secreted modular calcium-binding protein 2 (SMOC-2); SMOC-2, also termed SPARC-related modular calcium-binding protein 2, or smooth muscle-associated protein 2 (SMAP-2), is a ubiquitously expressed matricellular protein that enhances the response to angiogenic growth factors, mediate cell adhesion, keratinocyte migration, and metastasis. It is also associated with vitiligo and craniofacial and dental defects. Moreover, SMOC-2 acts as an Arf1 GTPase-activating protein (GAP) that interacts with clathrin heavy chain (CHC) and clathrin assembly protein CALM and functions in the retrograde, early endosome/trans-Golgi network (TGN) pathway in a clathrin- and AP-1-dependent manner. It also contributes to mitogenesis via activation of integrin-linked kinase (ILK). SMOC-2 contains a follistatin-like (FS) domain, two thyroglobulin-like (TY) domains, a novel domain, which is found only in the homologous SMOC-1, and an extracellular calcium-binding (EC) domain with two EF-hand calcium-binding motifs.


Pssm-ID: 320020  Cd Length: 114  Bit Score: 45.83  E-value: 4.98e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 190194423 592 VHWQFSELDQHPMDRVlTHSELAP----LRASLVPmEHCITRFFEECDPNKDKHITLKEWGHCFGI 653
Cdd:cd16241   49 VHWYFKQLDKNSSGDI-GKKEIKPfkrfLRKKSKP-KKCVKKFVEYCDVNNDKSLSVQELMGCLGV 112
FOLN smart00274
Follistatin-N-terminal domain-like; Follistatin-N-terminal domain-like, EGF-like. Region ...
 432-455 5.56e-06

Follistatin-N-terminal domain-like; Follistatin-N-terminal domain-like, EGF-like. Region distinct from the kazal-like sequence


Pssm-ID: 128570  Cd Length: 24  Bit Score: 43.04  E-value: 5.56e-06
                           10        20
                   ....*....|....*....|....
gi 190194423   432 SCMSFQCKRGHICKADQQGKPHCV 455
Cdd:smart00274   1 SCRNVQCPFGKVCVVDKNGNARCV 24
EFh_SPARC_TICN2 cd16238
EF-hand, extracellular calcium-binding (EC) motif, found in testican-2 (TICN2); TICN2, also ...
 592-651 7.93e-06

EF-hand, extracellular calcium-binding (EC) motif, found in testican-2 (TICN2); TICN2, also termed SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycan 2 (Spock2), is an extracellular heparan sulphate proteoglycan expressed in brain, lung, and testis. It inhibits neurite extension from cultured primary cerebellar neurons and may play regulatory roles in the development of the central nervous system. It also participates in diverse steps of neurogenesis. Moreover, TICN2 may contribute to ECM remodeling by regulating function(s) of other testican family members, which possess membrane-type matrix metalloproteinases (MT-MMPs) inhibitory function. Furthermore, TICN2 corresponding gene SPOCK2 acts as a susceptibility gene for bronchopulmonary dysplasia. TICN2 contains an N-terminal signal peptide, a testican-specific domain followed by a follistatin-like (FS) domain, an extracellular calcium-binding (EC) domain including a pair of EF hands, a thyroglobulin-like domain (TY), and a C-terminal region with two putative glycosaminoglycan attachment sites. The substitution of a ligating Asp residue by Tyr292 in the +Y position of EF-hand 2 in TICN2 could prevent Ca2+ binding to this site and also cause EF-hand 1 to bind one Ca2+ ion with low affinity.


Pssm-ID: 320017  Cd Length: 112  Bit Score: 45.31  E-value: 7.93e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423 592 VHWQFSELDQHPmDRVLTHSELAPLraSLVPMEHCITRFFEECDPNKDKHITLKEWGHCF 651
Cdd:cd16238   52 IGWMFSKLDTSG-DLFLDQAELAAI--NLDKYEVCIRPFFNSCDTYRDGRVSTAEWCFCF 108
PRK08581 PRK08581
amidase domain-containing protein;
1-297 1.08e-04

amidase domain-containing protein;


Pssm-ID: 236304 [Multi-domain]  Cd Length: 619  Bit Score: 45.55  E-value: 1.08e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423   1 MKTGLFFLCLLGTAAAIPTnarLLSDHSKPTAETVAPDNTAIPSLRAEAEENEKETAVSTEDDSHHKAEKSSVLKSKEES 80
Cdd:PRK08581   1 MKKNKILIYLLSTTLVLPT---LTSPTAYADDPQKDSTAKTTSHDSKKSNDDETSKDTSSKDTDKADNNNTSNQDNNDKK 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423  81 HEQSAEQGKSSSQelgLKDQEDSDGHLSVNLEYAPTEGTLDiKEDMSEPQEKKLSENtdflapgvSSFTDSNQQESITKR 160
Cdd:PRK08581  78 FSTIDSSTSDSNN---IIDFIYKNLPQTNINQLLTKNKYDD-NYSLTTLIQNLFNLN--------SDISDYEQPRNSEKS 145

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423 161 EENQEQPRNYSHHQLNRSSKHSQGLRDQGNQEQDPNISNGEEEEEKEPGEVGTHNDNQERKTELPREHANSKQEEDNTQS 240
Cdd:PRK08581 146 TNDSNKNSDSSIKNDTDTQSSKQDKADNQKAPSSNNTKPSTSNKQPNSPKPTQPNQSNSQPASDDTANQKSSSKDNQSMS 225

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 190194423 241 DDILEES-DQPTQVSKMQEDEFD-QGNQEQEDNSNAEMEEENASNVNKHiQETEWQSQE 297
Cdd:PRK08581 226 DSALDSIlDQYSEDAKKTQKDYAsQSKKDKTETSNTKNPQLPTQDELKH-KSKPAQSFE 283
Agg_substance NF033875
LPXTG-anchored aggregation substance; Aggregation substances, as described in Enterococcus, ...
 5-309 3.32e-04

LPXTG-anchored aggregation substance; Aggregation substances, as described in Enterococcus, are LPXTG-anchored large surface proteins that contribute to virulence. Several closely related paralogs may be found in a single strain.


Pssm-ID: 411439 [Multi-domain]  Cd Length: 1306  Bit Score: 43.93  E-value: 3.32e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423    5 LFFLCLLGTAAAIPTNARLLSDHSKPTAETVAPDNtaiPSLRAEAEEneKETAVSTE----DDSHHKAEKSSVLKSKEES 80
Cdd:NF033875   25 ILFLGVLGVVGLATDNVQAAELDTQPGTTTVQPDN---PDPQSGSET--PKTAVSEEatvqKDTTSQPTKVEEVASEKNG 99

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423   81 HEQS---------AEQ----GKSSSQELGLKDQEDSDGHLSVNLEYAPTEGtlDIKEDMSEPQEkklsentdFLAPGVSS 147
Cdd:NF033875  100 AEQSsatpndttnAQQptvgAEKSAQEQPVVSPETTNEPLGQPTEVAPAEN--EANKSTSIPKE--------FETPDVDK 169

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423  148 FTDSNQQE-SITKREENQEQPRNYSHHQLNRSSKHSqglrDQGNQEQDPNISNGEEEEEKEPGEVGTHN-----DNQERK 221
Cdd:NF033875  170 AVDEAKKDpNITVVEKPAEDLGNVSSKDLAAKEKEV----DQLQKEQAKKIAQQAAELKAKNEKIAKENaeiaaKNKAEK 245

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 190194423  222 TELPRE------HANSKQEEDNTQSDDILEESDQPTQVSK---------MQEDEFDQGNQEQEDNSNAEMEEENASNVNK 286
Cdd:NF033875  246 ERYEKEvaeynkHKNENGYVNEAISKNLVFDQSVVTKDTKissikggkfIKATDFNKVNAGDSKDIFTKLSKDMGGKATG 325

                         330       340
                  ....*....|....*....|....
gi 190194423  287 HIQETEWQSQE-GKTGLEAISNHK 309
Cdd:NF033875  326 NFQNSFVKEANlGSNGGYAVLLEK 349
EFh_SPARC_TICN1 cd16237
EF-hand, extracellular calcium-binding (EC) motif, found in testican-1 (TICN1); TICN1, also ...
 594-651 4.09e-04

EF-hand, extracellular calcium-binding (EC) motif, found in testican-1 (TICN1); TICN1, also termed protein SPOCK, or SPARC/osteonectin, CWCV, and Kazal-like domains proteoglycan 1 (Spock1), is a secreted chimeric proteoglycan that is highly expressed in brain and carries both chondroitin and heparan sulfate glycosaminoglycan side chains. It promotes resistance against Pseudomonas aeruginosa-induced keratitis through regulation of matrix metalloproteinase (MMP)-2 expression and activation. It also acts as a potential cancer prognostic marker that promotes the proliferation and metastasis of gallbladder cancer cells by activating the PI3K/Akt pathway. Moreover, TICN1 corresponding gene SPOCK1 is a novel transforming growth factor-beta target gene that regulates lung cancer cell epithelial-mesenchymal transition. It is also up-regulated by chromodomain helicase/adenosine triphosphatase DNA binding protein 1-like (CHD1L), and promotes human hepatocellular carcinoma (HCC) cell invasiveness and metastasis. Furthermore, TICN1 inhibits the lysosomal cysteine protease cathepsin L in intracellular vesicles and in the extracellular milieu. TICN1 contains an N-terminal signal sequence known to direct nascent polypeptides to the extracellular space, an unique region to the testicans, a follistatin (FS)-like domain generally involving five disulfide bridges, an extracellular calcium-binding (EC) domain including a pair of EF hands, and a thyroglobulin type-1 (TY) domain followed by a C-terminal acidic region with high density of negatively charged amino acids. The substitution of a ligating Asp residue by Phe291 in the +Y position of EF-hand 2 in TICN1 could prevent Ca2+ binding to this site and also cause EF-hand 1 to bind one Ca2+ ion with low affinity.


Pssm-ID: 320016  Cd Length: 112  Bit Score: 40.41  E-value: 4.09e-04
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 190194423 594 WQFSELDQHpMDRVLTHSELAPLRasLVPMEHCITRFFEECDPNKDKHITLKEWGHCF 651
Cdd:cd16237   54 WMFNKLDMN-YDLLLDPSEISAIY--LDKYEPCMKPLFNSCDSFKDGKLSNNEWCYCF 108
KAZAL_PSTI cd01327
Kazal-type pancreatic secretory trypsin inhibitors (PSTI) and related proteins, including the ...
 462-485 5.20e-03

Kazal-type pancreatic secretory trypsin inhibitors (PSTI) and related proteins, including the second domain of the ovomucoid turkey inhibitor and the C-terminal domain of the esophagus cancer-related gene-2 protein (ECRG-2), are members of the superfamily of kazal-type proteinase inhibitors and follistatin-like proteins.


Pssm-ID: 238648  Cd Length: 45  Bit Score: 35.34  E-value: 5.20e-03
                         10        20
                 ....*....|....*....|....
gi 190194423 462 CPptKPLDQVCGTDNQTYASSCHL 485
Cdd:cd01327    5 CP--KDYDPVCGTDGVTYSNECLL 26
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
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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