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Conserved domains on  [gi|44680154|ref|NP_057240|]
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myotubularin-related protein 2 isoform 1 [Homo sapiens]

Protein Classification

PH-like and Myotub-related domain-containing protein (domain architecture ID 10352270)

PH-like and Myotub-related domain-containing protein

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
208-528 0e+00

Myotubularin-like phosphatase domain; This family represents the phosphatase domain within eukaryotic myotubularin-related proteins. Myotubularin is a dual-specific lipid phosphatase that dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol (3,5)-bi-phosphate. Mutations in gene encoding myotubularin-related proteins have been associated with disease.


:

Pssm-ID: 310891  Cd Length: 321  Bit Score: 617.95  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154   208 LYDPLLEYRRQGIPNES-WRITKINERYELCDTYPALLVVPANIPDEELKRVASFRSRGRIPVLSWIHPESQATITRCSQ 286
Cdd:pfam06602   1 LYDPEKEFARLGLPSKDgWRISDINKDYKLCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHKENGAVITRSSQ 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154   287 PMVGVSGKRSKEDEKYLQAIMDSnaqSHKIFIFDARPSVNAVANKAKGGGYESEDAYQNAELVFLDIHNIHVMRESLRKL 366
Cdd:pfam06602  81 PLVGLNGKRSIEDEKLLNAIFSA---SKKLYIVDARPTINAMANRAKGGGTENEDNYPNCKKVFLGIDNIHVMRDSLNKL 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154   367 KEIVY-PNIEETHWLSNLESTHWLEHIKLILAGALRIADKVESGKTSVVVHCSDGWDRTAQLTSLAMLMLDGYYRTIRGF 445
Cdd:pfam06602 158 VEACRdSSSSMDRWLSRLESSGWLKHIKAILDGACLIAQCVHLEGSSVLVHCSDGWDRTAQLTSLAQLLLDPYYRTIEGF 237
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154   446 EVLVEKEWLSFGHRFQLRVGHGDKNHADADRSPVFLQFIDCVWQMTRQFPTAFEFNEYFLITILDHLYSCLFGTFLCNSE 525
Cdd:pfam06602 238 QVLIEKEWLSFGHKFADRCGHLASESGSKERSPVFLQFLDCVWQLLRQFPCAFEFNERFLIRLLDHLYSCQFGTFLCNSE 317

                  ...
gi 44680154   526 QQR 528
Cdd:pfam06602 318 KER 320
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
73-187 1.25e-78

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.


The actual alignment was detected with superfamily member cd13356:

Pssm-ID: 327399  Cd Length: 115  Bit Score: 248.45  E-value: 1.25e-78
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154  73 MEEPPLLPGENIKDMAKDVTYICPFTGAVRGTLTVTNYRLYFKSMERDPPFVLDASLGVINRVEKIGGASSRGENSYGLE 152
Cdd:cd13356   1 MEEPPLLPGENIKDMAKDVTYICPFTGAVRGTLTVTNYRLYFKSMERDPPFVLDASLGVINRVEKIGGASSRGENSYGLE 80
                        90       100       110
                ....*....|....*....|....*....|....*
gi 44680154 153 TVCKDIRNLRFAHKPEGRTRRSIFENLMKYAFPVS 187
Cdd:cd13356  81 TVCKDIRNLRFAHKPEGRTRRSIFENLMKYAFPVS 115
 
Name Accession Description Interval E-value
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
208-528 0e+00

Myotubularin-like phosphatase domain; This family represents the phosphatase domain within eukaryotic myotubularin-related proteins. Myotubularin is a dual-specific lipid phosphatase that dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol (3,5)-bi-phosphate. Mutations in gene encoding myotubularin-related proteins have been associated with disease.


Pssm-ID: 310891  Cd Length: 321  Bit Score: 617.95  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154   208 LYDPLLEYRRQGIPNES-WRITKINERYELCDTYPALLVVPANIPDEELKRVASFRSRGRIPVLSWIHPESQATITRCSQ 286
Cdd:pfam06602   1 LYDPEKEFARLGLPSKDgWRISDINKDYKLCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHKENGAVITRSSQ 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154   287 PMVGVSGKRSKEDEKYLQAIMDSnaqSHKIFIFDARPSVNAVANKAKGGGYESEDAYQNAELVFLDIHNIHVMRESLRKL 366
Cdd:pfam06602  81 PLVGLNGKRSIEDEKLLNAIFSA---SKKLYIVDARPTINAMANRAKGGGTENEDNYPNCKKVFLGIDNIHVMRDSLNKL 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154   367 KEIVY-PNIEETHWLSNLESTHWLEHIKLILAGALRIADKVESGKTSVVVHCSDGWDRTAQLTSLAMLMLDGYYRTIRGF 445
Cdd:pfam06602 158 VEACRdSSSSMDRWLSRLESSGWLKHIKAILDGACLIAQCVHLEGSSVLVHCSDGWDRTAQLTSLAQLLLDPYYRTIEGF 237
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154   446 EVLVEKEWLSFGHRFQLRVGHGDKNHADADRSPVFLQFIDCVWQMTRQFPTAFEFNEYFLITILDHLYSCLFGTFLCNSE 525
Cdd:pfam06602 238 QVLIEKEWLSFGHKFADRCGHLASESGSKERSPVFLQFLDCVWQLLRQFPCAFEFNERFLIRLLDHLYSCQFGTFLCNSE 317

                  ...
gi 44680154   526 QQR 528
Cdd:pfam06602 318 KER 320
PH-GRAM_MTMR2_mammal-like cd13356
Myotubularian related 2 protein (MTMR2) Pleckstrin Homology-Glucosyltransferases, Rab-like ...
73-187 1.25e-78

Myotubularian related 2 protein (MTMR2) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR2 is a member of the myotubularin protein phosphatase gene family. MTMR2 binds to phosphoinositide lipids through its PH-GRAM domain, and can hydrolyze phosphatidylinositol(3)-phosphate and phosphatidylinositol(3,5)-biphosphate in vitro. Mutations in MTMR2 are a cause of Charcot-Marie-Tooth disease type 4B, an autosomal recessive demyelinating neuropathy. The protein can self-associate and form heteromers with MTMR5 and MTMR12. MTMR2 contains a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an active PTP domain, a SET-interaction domain, a coiled-coil region, and a C-terminal PDZ domain. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 6 of the 13 MTMRs (MTMRs 5, 9-13) contain naturally occurring substitutions of residues required for catalysis by PTP family enzymes. Although these proteins are predicted to be enzymatically inactive, they are thought to function as antagonists of endogenous phosphatase activity or interaction modules. Most MTMRs contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, a PTP domain (which may be active or inactive), a SET-interaction domain, and a C-terminal coiled-coil region. In addition some members contain DENN domain N-terminal to the PH-GRAM domain and FYVE, PDZ, and PH domains C-terminal to the coiled-coil region. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. The PH domain family possesses multiple functions including the ability to bind phosphoinositides via its beta1/beta2, beta3/beta4, and beta6/beta7 connecting loops and to other proteins. However, no phosphoinositide binding sites have been found for the MTMRs to date.Members in this cd include mammals, chickens, anoles, human body lice, and aphids.


Pssm-ID: 270163  Cd Length: 115  Bit Score: 248.45  E-value: 1.25e-78
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154  73 MEEPPLLPGENIKDMAKDVTYICPFTGAVRGTLTVTNYRLYFKSMERDPPFVLDASLGVINRVEKIGGASSRGENSYGLE 152
Cdd:cd13356   1 MEEPPLLPGENIKDMAKDVTYICPFTGAVRGTLTVTNYRLYFKSMERDPPFVLDASLGVINRVEKIGGASSRGENSYGLE 80
                        90       100       110
                ....*....|....*....|....*....|....*
gi 44680154 153 TVCKDIRNLRFAHKPEGRTRRSIFENLMKYAFPVS 187
Cdd:cd13356  81 TVCKDIRNLRFAHKPEGRTRRSIFENLMKYAFPVS 115
GRAM pfam02893
GRAM domain; The GRAM domain is found in in glucosyltransferases, myotubularins and other ...
77-185 1.31e-23

GRAM domain; The GRAM domain is found in in glucosyltransferases, myotubularins and other putative membrane-associated proteins. Note the alignment is lacking the last two beta strands and alpha helix.


Pssm-ID: 308507  Cd Length: 106  Bit Score: 97.41  E-value: 1.31e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154    77 PLLPGENIKDmakdvTYICPF---TGAVRGTLTVTNYRLYFKSMERDPPFVLDASLGVINRVEKIGGASSRGENSYGLET 153
Cdd:pfam02893   1 TLPPGERLIA-----DYSCYLlrdGGPVQGRLYLTNYRLCFRSLPLGWSTKVVIPLADIERIEKLTGAASLFPNGIQVET 75
                          90       100       110
                  ....*....|....*....|....*....|..
gi 44680154   154 VCKDiRNLRFAHKPEGRTRRSIFENLMKYAFP 185
Cdd:pfam02893  76 GSKD-LELRFAGFVSRDEAFEFILRLLKNAHP 106
GRAM smart00568
domain in glucosyltransferases, myotubularins and other putative membrane-associated proteins;
77-139 1.27e-10

domain in glucosyltransferases, myotubularins and other putative membrane-associated proteins;


Pssm-ID: 214725  Cd Length: 60  Bit Score: 59.14  E-value: 1.27e-10
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 44680154     77 PLLPGENIKDmakdvTYICPF--TGAVRGTLTVTNYRLYFKSMERDPPFVLDASLGVINRVEKIG 139
Cdd:smart00568   1 KLPEEEKLIA-----DYSCYLsrTGPVQGRLYISNYRLCFRSNLPGKLTKVVIPLADITRIEKST 60
PTPc_DSPc smart00012
Protein tyrosine phosphatase, catalytic domain, undefined specificity; Protein tyrosine ...
407-513 4.87e-07

Protein tyrosine phosphatase, catalytic domain, undefined specificity; Protein tyrosine phosphatases. Homologues detected by this profile and not by those of "PTPc" or "DSPc" are predicted to be protein phosphatases with a similar fold to DSPs and PTPs, yet with unpredicted specificities.


Pssm-ID: 214469  Cd Length: 105  Bit Score: 49.28  E-value: 4.87e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154    407 ESGKTSVVVHCSDGWDRTAQLTSLAMLMLDGYYRTIrgfevlvekewlsfghrfqlrvghgdknhadadrspvFLQFIDC 486
Cdd:smart00012  36 SESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEAG-------------------------------------EVDIFDT 78
                           90       100
                   ....*....|....*....|....*..
gi 44680154    487 VWQMTRQFPTAFEFNEYFLITILDHLY 513
Cdd:smart00012  79 VKELRSQRPGMVQTEEQYLFLYRALLE 105
 
Name Accession Description Interval E-value
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
208-528 0e+00

Myotubularin-like phosphatase domain; This family represents the phosphatase domain within eukaryotic myotubularin-related proteins. Myotubularin is a dual-specific lipid phosphatase that dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol (3,5)-bi-phosphate. Mutations in gene encoding myotubularin-related proteins have been associated with disease.


Pssm-ID: 310891  Cd Length: 321  Bit Score: 617.95  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154   208 LYDPLLEYRRQGIPNES-WRITKINERYELCDTYPALLVVPANIPDEELKRVASFRSRGRIPVLSWIHPESQATITRCSQ 286
Cdd:pfam06602   1 LYDPEKEFARLGLPSKDgWRISDINKDYKLCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHKENGAVITRSSQ 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154   287 PMVGVSGKRSKEDEKYLQAIMDSnaqSHKIFIFDARPSVNAVANKAKGGGYESEDAYQNAELVFLDIHNIHVMRESLRKL 366
Cdd:pfam06602  81 PLVGLNGKRSIEDEKLLNAIFSA---SKKLYIVDARPTINAMANRAKGGGTENEDNYPNCKKVFLGIDNIHVMRDSLNKL 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154   367 KEIVY-PNIEETHWLSNLESTHWLEHIKLILAGALRIADKVESGKTSVVVHCSDGWDRTAQLTSLAMLMLDGYYRTIRGF 445
Cdd:pfam06602 158 VEACRdSSSSMDRWLSRLESSGWLKHIKAILDGACLIAQCVHLEGSSVLVHCSDGWDRTAQLTSLAQLLLDPYYRTIEGF 237
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154   446 EVLVEKEWLSFGHRFQLRVGHGDKNHADADRSPVFLQFIDCVWQMTRQFPTAFEFNEYFLITILDHLYSCLFGTFLCNSE 525
Cdd:pfam06602 238 QVLIEKEWLSFGHKFADRCGHLASESGSKERSPVFLQFLDCVWQLLRQFPCAFEFNERFLIRLLDHLYSCQFGTFLCNSE 317

                  ...
gi 44680154   526 QQR 528
Cdd:pfam06602 318 KER 320
PH-GRAM_MTMR2_mammal-like cd13356
Myotubularian related 2 protein (MTMR2) Pleckstrin Homology-Glucosyltransferases, Rab-like ...
73-187 1.25e-78

Myotubularian related 2 protein (MTMR2) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR2 is a member of the myotubularin protein phosphatase gene family. MTMR2 binds to phosphoinositide lipids through its PH-GRAM domain, and can hydrolyze phosphatidylinositol(3)-phosphate and phosphatidylinositol(3,5)-biphosphate in vitro. Mutations in MTMR2 are a cause of Charcot-Marie-Tooth disease type 4B, an autosomal recessive demyelinating neuropathy. The protein can self-associate and form heteromers with MTMR5 and MTMR12. MTMR2 contains a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an active PTP domain, a SET-interaction domain, a coiled-coil region, and a C-terminal PDZ domain. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 6 of the 13 MTMRs (MTMRs 5, 9-13) contain naturally occurring substitutions of residues required for catalysis by PTP family enzymes. Although these proteins are predicted to be enzymatically inactive, they are thought to function as antagonists of endogenous phosphatase activity or interaction modules. Most MTMRs contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, a PTP domain (which may be active or inactive), a SET-interaction domain, and a C-terminal coiled-coil region. In addition some members contain DENN domain N-terminal to the PH-GRAM domain and FYVE, PDZ, and PH domains C-terminal to the coiled-coil region. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. The PH domain family possesses multiple functions including the ability to bind phosphoinositides via its beta1/beta2, beta3/beta4, and beta6/beta7 connecting loops and to other proteins. However, no phosphoinositide binding sites have been found for the MTMRs to date.Members in this cd include mammals, chickens, anoles, human body lice, and aphids.


Pssm-ID: 270163  Cd Length: 115  Bit Score: 248.45  E-value: 1.25e-78
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154  73 MEEPPLLPGENIKDMAKDVTYICPFTGAVRGTLTVTNYRLYFKSMERDPPFVLDASLGVINRVEKIGGASSRGENSYGLE 152
Cdd:cd13356   1 MEEPPLLPGENIKDMAKDVTYICPFTGAVRGTLTVTNYRLYFKSMERDPPFVLDASLGVINRVEKIGGASSRGENSYGLE 80
                        90       100       110
                ....*....|....*....|....*....|....*
gi 44680154 153 TVCKDIRNLRFAHKPEGRTRRSIFENLMKYAFPVS 187
Cdd:cd13356  81 TVCKDIRNLRFAHKPEGRTRRSIFENLMKYAFPVS 115
PH-GRAM_MTM-like cd13223
Myotubularian 1 and related proteins Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase; ...
86-185 3.34e-57

Myotubularian 1 and related proteins Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase; MTM1, MTMR1, and MTMR2 are members of the myotubularin protein phosphatase gene family. They contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an active PTP domain, a SET-interaction domain, and a C-terminal coiled-coil region. In addition MTMR1 (Myotubularian related 1 protein) and MTMR2 (Myotubularian related 2 protein) contain a C-terminal PDZ domain. Mutations in MTMR2 are a cause of Charcot-Marie-Tooth disease type 4B, an autosomal recessive demyelinating neuropathy. The protein can self-associate and form heteromers with MTMR5 and MTMR12. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. The PH domain family possesses multiple functions including the ability to bind phosphoinositides via its beta1/beta2, beta3/beta4, and beta6/beta7 connecting loops and to other proteins. However, no phosphoinositide binding sites have been found for the MTMRs to date.


Pssm-ID: 275407  Cd Length: 100  Bit Score: 190.53  E-value: 3.34e-57
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154  86 DMAKDVTYICPFTGAVRGTLTVTNYRLYFKSMERDPPFVLDASLGVINRVEKIGGASSRGENSYGLETVCKDIRNLRFAH 165
Cdd:cd13223   1 LKEKDVTYLCPFRGPVRGTLYITNYRLYFKSRDREPNFVLDVPLGVISRVEKVGGATSRGENSYGLEIHCKDMRNLRFAH 80
                        90       100
                ....*....|....*....|
gi 44680154 166 KPEGRTRRSIFENLMKYAFP 185
Cdd:cd13223  81 KQENHSRRKLYETLQKYAFP 100
PH-GRAM_MTMR2_insect-like cd13357
Myotubularian related 2 protein (MTMR2) Pleckstrin Homology-Glucosyltransferases, Rab-like ...
86-185 2.27e-55

Myotubularian related 2 protein (MTMR2) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR2 is a member of the myotubularin protein phosphatase gene family. MTMR2 binds to phosphoinositide lipids through its PH-GRAM domain, and can hydrolyze phosphatidylinositol(3)-phosphate and phosphatidylinositol(3,5)-biphosphate in vitro. Mutations in MTMR2 are a cause of Charcot-Marie-Tooth disease type 4B, an autosomal recessive demyelinating neuropathy. The protein can self-associate and form heteromers with MTMR5 and MTMR12. MTMR2 contains a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an active PTP domain, a SET-interaction domain, a coiled-coil region, and a C-terminal PDZ domain. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 6 of the 13 MTMRs (MTMRs 5, 9-13) contain naturally occurring substitutions of residues required for catalysis by PTP family enzymes. Although these proteins are predicted to be enzymatically inactive, they are thought to function as antagonists of endogenous phosphatase activity or interaction modules. Most MTMRs contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, a PTP domain (which may be active or inactive), a SET-interaction domain, and a C-terminal coiled-coil region. In addition some members contain DENN domain N-terminal to the PH-GRAM domain and FYVE, PDZ, and PH domains C-terminal to the coiled-coil region. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. The PH domain family possesses multiple functions including the ability to bind phosphoinositides via its beta1/beta2, beta3/beta4, and beta6/beta7 connecting loops and to other proteins. However, no phosphoinositide binding sites have been found for the MTMRs to date. Members in this cd include Drosophila, sea urchins, mosquitos, bees, ticks, and anemones.


Pssm-ID: 270164  Cd Length: 100  Bit Score: 185.40  E-value: 2.27e-55
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154  86 DMAKDVTYICPFTGAVRGTLTVTNYRLYFKSMERDPPFVLDASLGVINRVEKIGGASSRGENSYGLETVCKDIRNLRFAH 165
Cdd:cd13357   1 AIAKDVTYLCPFRGPVRGTLTITNYKLYFKSLDREPPFTVEVPLGVIYRVEKVGGATSRGENSYGLEIFCKDMRNLRFAH 80
                        90       100
                ....*....|....*....|
gi 44680154 166 KPEGRTRRSIFENLMKYAFP 185
Cdd:cd13357  81 KQENHSRRLVFEKLQAYAFP 100
PH-GRAM_MTMR1 cd13358
Myotubularian related 1 protein (MTMR1) Pleckstrin Homology-Glucosyltransferases, Rab-like ...
85-185 2.86e-48

Myotubularian related 1 protein (MTMR1) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR1 is a member of the myotubularin protein phosphatase gene family. MTMR1 binds to phosphoinositide lipids through its PH-GRAM domain, and can hydrolyze phosphatidylinositol(3)-phosphate and phosphatidylinositol(3,5)-biphosphate in vitro. MTMR1 contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an active PTP domain, a SET-interaction domain, a coiled-coil region, and a C-terminal PDZ domain. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 6 of the 13 MTMRs (MTMRs 5, 9-13) contain naturally occurring substitutions of residues required for catalysis by PTP family enzymes. Although these proteins are predicted to be enzymatically inactive, they are thought to function as antagonists of endogenous phosphatase activity or interaction modules. Most MTMRs contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, a PTP domain (which may be active or inactive), a SET-interaction domain, and a C-terminal coiled-coil region. In addition some members contain DENN domain N-terminal to the PH-GRAM domain and FYVE, PDZ, and PH domains C-terminal to the coiled-coil region. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. The PH domain family possesses multiple functions including the ability to bind phosphoinositides via its beta1/beta2, beta3/beta4, and beta6/beta7 connecting loops and to other proteins. However, no phosphoinositide binding sites have been found for the MTMRs to date.


Pssm-ID: 270165  Cd Length: 100  Bit Score: 165.85  E-value: 2.86e-48
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154  85 KDMAKDVTYICPFTGAVRGTLTVTNYRLYFKSMERDPPFVLDASLGVINRVEKIgGASSRGENSYGLETVCKDIRNLRFA 164
Cdd:cd13358   1 KAIVKDVMYICPFMGAVSGTLTVTDFKMYFKNVERDPPFILDVPLGVISRVEKI-GVQSHGDNSCGIEIVCKDMRNLRLA 79
                        90       100
                ....*....|....*....|.
gi 44680154 165 HKPEGRTRRSIFENLMKYAFP 185
Cdd:cd13358  80 YKQEEQSKLEIFENLNKHAFP 100
PH-GRAM_MTM1 cd13355
Myotubularian 1 protein (MTM1) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase ...
89-185 4.43e-47

Myotubularian 1 protein (MTM1) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTM1 is a member of the myotubularin protein phosphatase gene family. It is required for muscle cell differentiation and mutations in this gene have been identified as being responsible for X-linked myotubular myopathy, a severe congenital muscle disorder characterized by defective muscle cell development. Since its initial discovery, there have been an additional 14 myotubularin-related proteins identified. MTM1 binds to phosphoinositide lipids through its PH-GRAM domain, and can hydrolyze phosphatidylinositol(3)-phosphate and phosphatidylinositol(3,5)-biphosphate in vitro. The protein can self-associate and form heteromers with MTMR12. MTM1 contains a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an active PTP domain, a SET-interaction domain, and a C-terminal coiled-coil region. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. All MTMRs contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, a PTP domain (which may be active or inactive), a SET-interaction domain, and a C-terminal coiled-coil region. In addition some members contain DENN domain N-terminal to the PH-GRAM domain and FYVE and PH domains C-terminal to the coiled-coil region.


Pssm-ID: 270162  Cd Length: 100  Bit Score: 162.33  E-value: 4.43e-47
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154  89 KDVTYICPFTGAVRGTLTVTNYRLYFKSMERDPPFVLDASLGVINRVEKIGGASSRGENSYGLETVCKDIRNLRFAHKPE 168
Cdd:cd13355   4 KDVIYICPFNGPVKGRVYITNYRLYFKSTESEPPVTLDVPLGVISRIEKMGGASSRGENSYGLDITCKDMRNLRFALKQE 83
                        90
                ....*....|....*..
gi 44680154 169 GRTRRSIFENLMKYAFP 185
Cdd:cd13355  84 GHSRRDIFEILTKYAFP 100
GRAM pfam02893
GRAM domain; The GRAM domain is found in in glucosyltransferases, myotubularins and other ...
77-185 1.31e-23

GRAM domain; The GRAM domain is found in in glucosyltransferases, myotubularins and other putative membrane-associated proteins. Note the alignment is lacking the last two beta strands and alpha helix.


Pssm-ID: 308507  Cd Length: 106  Bit Score: 97.41  E-value: 1.31e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154    77 PLLPGENIKDmakdvTYICPF---TGAVRGTLTVTNYRLYFKSMERDPPFVLDASLGVINRVEKIGGASSRGENSYGLET 153
Cdd:pfam02893   1 TLPPGERLIA-----DYSCYLlrdGGPVQGRLYLTNYRLCFRSLPLGWSTKVVIPLADIERIEKLTGAASLFPNGIQVET 75
                          90       100       110
                  ....*....|....*....|....*....|..
gi 44680154   154 VCKDiRNLRFAHKPEGRTRRSIFENLMKYAFP 185
Cdd:pfam02893  76 GSKD-LELRFAGFVSRDEAFEFILRLLKNAHP 106
PH-GRAM cd10570
Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins ...
86-179 9.63e-19

Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 6 of the 13 MTMRs (MTMRs 5, 9-13) contain naturally occurring substitutions of residues required for catalysis by PTP family enzymes. Although these proteins are predicted to be enzymatically inactive, they are thought to function as antagonists of endogenous phosphatase activity or interaction modules. Most MTMRs contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, a PTP domain (which may be active or inactive), a SET-interaction domain, and a C-terminal coiled-coil region. In addition some members contain DENN domain N-terminal to the PH-GRAM domain and FYVE, PDZ, and PH domains C-terminal to the coiled-coil region. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold.


Pssm-ID: 275393  Cd Length: 94  Bit Score: 83.20  E-value: 9.63e-19
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154  86 DMAKDVTYIC---PFTGAVRGTLTVTNYRLYFKSMERDPPFVLDASLGVINRVEKIGGASSrgeNSYGLETVCKDIRNLR 162
Cdd:cd10570   1 IEKLGVRFCCalrPRKLPLEGTLYLSTYRLIFSSKADGDETKLVIPLVDITDVEKIAGASF---LPSGLIITCKDFRTIK 77
                        90
                ....*....|....*..
gi 44680154 163 FAHKPEGRTRRSIFENL 179
Cdd:cd10570  78 FSFDSEDEAVKVIARVL 94
GRAM smart00568
domain in glucosyltransferases, myotubularins and other putative membrane-associated proteins;
77-139 1.27e-10

domain in glucosyltransferases, myotubularins and other putative membrane-associated proteins;


Pssm-ID: 214725  Cd Length: 60  Bit Score: 59.14  E-value: 1.27e-10
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 44680154     77 PLLPGENIKDmakdvTYICPF--TGAVRGTLTVTNYRLYFKSMERDPPFVLDASLGVINRVEKIG 139
Cdd:smart00568   1 KLPEEEKLIA-----DYSCYLsrTGPVQGRLYISNYRLCFRSNLPGKLTKVVIPLADITRIEKST 60
PH-like cd00900
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
86-179 2.97e-08

Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like and IRS-like PTB domains, the ran-binding domain, the EVH1 domain, a domain in neurobeachin and the third domain of FERM. All of these domains have a PH fold, but lack significant sequence similarity. They are generally involved in targeting to protein to the appropriate cellular location or interacting with a binding partner. This domain family possesses multiple functions including the ability to bind inositol phosphates and to other proteins.


Pssm-ID: 275390  Cd Length: 89  Bit Score: 52.79  E-value: 2.97e-08
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154  86 DMAKDVTYICPFTGAVRGTLTVTNYRLYFKSMErDPPFVLDASLGVINRVEKiggaSSRGENSYGLETVCKD-IRNLRFA 164
Cdd:cd00900   1 LKFRAVRVYREPTKRVEGTLYITSDRLILRDKN-DGGLELSIPISDIVNVNV----SPQGPSSRYLVLVLKDrGEFVGFS 75
                        90
                ....*....|....*
gi 44680154 165 HKPEgRTRRSIFENL 179
Cdd:cd00900  76 FPKE-EDAIEISDAL 89
PTPc_DSPc smart00012
Protein tyrosine phosphatase, catalytic domain, undefined specificity; Protein tyrosine ...
407-513 4.87e-07

Protein tyrosine phosphatase, catalytic domain, undefined specificity; Protein tyrosine phosphatases. Homologues detected by this profile and not by those of "PTPc" or "DSPc" are predicted to be protein phosphatases with a similar fold to DSPs and PTPs, yet with unpredicted specificities.


Pssm-ID: 214469  Cd Length: 105  Bit Score: 49.28  E-value: 4.87e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154    407 ESGKTSVVVHCSDGWDRTAQLTSLAMLMLDGYYRTIrgfevlvekewlsfghrfqlrvghgdknhadadrspvFLQFIDC 486
Cdd:smart00012  36 SESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEAG-------------------------------------EVDIFDT 78
                           90       100
                   ....*....|....*....|....*..
gi 44680154    487 VWQMTRQFPTAFEFNEYFLITILDHLY 513
Cdd:smart00012  79 VKELRSQRPGMVQTEEQYLFLYRALLE 105
PTPc_motif smart00404
Protein tyrosine phosphatase, catalytic domain motif;
407-513 4.87e-07

Protein tyrosine phosphatase, catalytic domain motif;


Pssm-ID: 214649  Cd Length: 105  Bit Score: 49.28  E-value: 4.87e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 44680154    407 ESGKTSVVVHCSDGWDRTAQLTSLAMLMLDGYYRTIrgfevlvekewlsfghrfqlrvghgdknhadadrspvFLQFIDC 486
Cdd:smart00404  36 SESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEAG-------------------------------------EVDIFDT 78
                           90       100
                   ....*....|....*....|....*..
gi 44680154    487 VWQMTRQFPTAFEFNEYFLITILDHLY 513
Cdd:smart00404  79 VKELRSQRPGMVQTEEQYLFLYRALLE 105
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.16
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
  • Marchler-Bauer A et al. (2015), "CDD: NCBI's conserved domain database.", Nucleic Acids Res.43(D)222-6.
  • Marchler-Bauer A et al. (2011), "CDD: a Conserved Domain Database for the functional annotation of proteins.", Nucleic Acids Res.39(D)225-9.
  • Marchler-Bauer A, Bryant SH (2004), "CD-Search: protein domain annotations on the fly.", Nucleic Acids Res.32(W)327-331.
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