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Conserved domains on  [gi|224994246|ref|NP_852074|]
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myotubularin-related protein 11 [Mus musculus]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PTP_DSP_cys super family cl28904
cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This ...
 259-449 2.84e-102

cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This superfamily is composed of cys-based phosphatases, which includes classical protein tyrosine phosphatases (PTPs) as well as dual-specificity phosphatases (DUSPs or DSPs). They are characterized by a CxxxxxR conserved catalytic loop (where C is the catalytic cysteine, x is any amino acid, and R is an arginine). PTPs are part of the tyrosine phosphorylation/dephosphorylation regulatory mechanism, and are important in the response of the cells to physiologic and pathologic changes in their environment. DUSPs show more substrate diversity (including RNA and lipids) and include pTyr, pSer, and pThr phosphatases.


The actual alignment was detected with superfamily member cd14595:

Pssm-ID: 475123  Cd Length: 195  Bit Score: 310.99  E-value: 2.84e-102
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 259 GRGPRLSWHHPGGSDLLRCGGFYIASDPNKEDIRAVESMLQAGHSDVVLVETMDEMPSLADIQLAHLKLRALCLPDSSVA 338
Cdd:cd14595    1 GRIPRWCWHHPGGSDLLRMAGFYTNSDPEKEDIRSVELLLQAGHSQCVIVDTSEELPSPADIQLAYLKLRTLCLPDISVS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 339 ED--KWLSALEGTRWLDYVRSCLRKASDISVLVTSRVRSVVLQELGDRDFNGLLSSLVQLLLAPEARTLFGFQSLVQREW 416
Cdd:cd14595   81 VSdeKWLSNLEGTRWLDHVRACLRKASEVSCLLAERHRSVILQESEDRDLNCLLSSLVQLLSDPHARTISGFQSLVQKEW 160

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 224994246 417 VAAGHPFLTRLGDTG--ASEEAPVFPLFLDCAWQL 449
Cdd:cd14595  161 VVAGHPFLQRLNLTResDKEESPVFLLFLDCVWQL 195
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
 51-165 1.89e-52

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 cd15790:

Pssm-ID: 473070  Cd Length: 123  Bit Score: 176.89  E-value: 1.89e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246  51 LPGEHILAWAPGRRK------GPGlDLPGTLICTNFRVTFQPCGWQR---KQDTPLSSENDFALINIGRLEAVSGLSRVQ 121
Cdd:cd15790    1 LPGEHILEEAVRVRKlvqwrdGEG-FLSGTLYCTNFRVAFVPEHIQKdenDHDTVLNSEHDIALPSIDRVVAVQGPTTMK 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 224994246 122 LLRPGSQLKFIPEELLLHGRDFRLLRVGFEAGGLAPQAFQVTMA 165
Cdd:cd15790   80 AVTASSGLKFIPEELVIYCRDFRLLRFQFEQSTLEPQAFQITTA 123
3-PAP super family cl13953
Myotubularin-associated protein; This domain family is found in eukaryotes, and is typically ...
 549-683 4.22e-26

Myotubularin-associated protein; This domain family is found in eukaryotes, and is typically between 115 and 138 amino acids in length. Myotubularin is a dual-specific phosphatase that dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol (3,5)-bisphosphate. 3-PAP is a catalytically inactive member of the myotubularin gene family, which coprecipitates lipid phosphatidylinositol 3-phosphate-3-phosphatase activity from lysates of human platelets.


The actual alignment was detected with superfamily member pfam12578:

Pssm-ID: 463634  Cd Length: 132  Bit Score: 103.99  E-value: 4.22e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246  549 RFSRQQQSLMVPGPPSSMwlfsrGTLTPLNQLCPWQDSSSLLAVSSHWLPrpARSSESlaDQEWGLPSHWGACPLPPGLL 628
Cdd:pfam12578   1 KRRKKSYSSTLRGPPPSL-----KNGLFRDEEDLLRRNSLLLRLKPDCPL--HRSSDS--NDSEQFFRDWFSKPADLHGL 71

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 224994246  629 -LPGYLGPQIRFWKRCYLRGRPEVQMGSSAL-----TVSALQDELSHLQELLRQWTPRISP 683
Cdd:pfam12578  72 lLPLLSGPHIKLWKLCYLRWVPEAQINHGGPitafhKLSLLADEVEALQRLLRQYRGGPSE 132
 
Name Accession Description Interval E-value
PTP-MTMR11 cd14595
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 259-449 2.84e-102

protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related phosphoinositide phosphatase 11; Myotubularin related phosphoinositide phosphatase 11 (MTMR11), also called cisplatin resistance-associated protein (hCRA) in humans, is enzymatically inactive and contains a C-terminal coiled-coil domain and an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. MTMR11 is a pseudophosphatase that lacks the catalytic cysteine in its catalytic pocket.


Pssm-ID: 350443  Cd Length: 195  Bit Score: 310.99  E-value: 2.84e-102
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 259 GRGPRLSWHHPGGSDLLRCGGFYIASDPNKEDIRAVESMLQAGHSDVVLVETMDEMPSLADIQLAHLKLRALCLPDSSVA 338
Cdd:cd14595    1 GRIPRWCWHHPGGSDLLRMAGFYTNSDPEKEDIRSVELLLQAGHSQCVIVDTSEELPSPADIQLAYLKLRTLCLPDISVS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 339 ED--KWLSALEGTRWLDYVRSCLRKASDISVLVTSRVRSVVLQELGDRDFNGLLSSLVQLLLAPEARTLFGFQSLVQREW 416
Cdd:cd14595   81 VSdeKWLSNLEGTRWLDHVRACLRKASEVSCLLAERHRSVILQESEDRDLNCLLSSLVQLLSDPHARTISGFQSLVQKEW 160

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 224994246 417 VAAGHPFLTRLGDTG--ASEEAPVFPLFLDCAWQL 449
Cdd:cd14595  161 VVAGHPFLQRLNLTResDKEESPVFLLFLDCVWQL 195
PH-GRAM_MTMR11 cd15790
Myotubularian (MTM) related 11 protein (MTMR11) Pleckstrin Homology-Glucosyltransferases, ...
 51-165 1.89e-52

Myotubularian (MTM) related 11 protein (MTMR11) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR10, MTMR11, and MTMR12 are catalytically inactive phosphatases that play a role as an adapter for the phosphatase myotubularin to regulate myotubularintracellular location. They contains a Glu residue instead of a conserved Cys residue in the dsPTPase catalytic loop which renders it catalytically inactive as a phosphatase. They contains an N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an inactive PTP domain, a SET interaction domain, and a C-terminal coiled-coil 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: 275433  Cd Length: 123  Bit Score: 176.89  E-value: 1.89e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246  51 LPGEHILAWAPGRRK------GPGlDLPGTLICTNFRVTFQPCGWQR---KQDTPLSSENDFALINIGRLEAVSGLSRVQ 121
Cdd:cd15790    1 LPGEHILEEAVRVRKlvqwrdGEG-FLSGTLYCTNFRVAFVPEHIQKdenDHDTVLNSEHDIALPSIDRVVAVQGPTTMK 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 224994246 122 LLRPGSQLKFIPEELLLHGRDFRLLRVGFEAGGLAPQAFQVTMA 165
Cdd:cd15790   80 AVTASSGLKFIPEELVIYCRDFRLLRFQFEQSTLEPQAFQITTA 123
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
 206-469 3.12e-46

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: 461958 [Multi-domain]  Cd Length: 332  Bit Score: 167.27  E-value: 3.12e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246  206 DWETECKKQGA---RGWRVSTVNERFDVATSLSGYFWVPNRILDSEVRRAFAHFHQGRGPRLSWHHPG-GSDLLRCG--- 278
Cdd:pfam06602   9 DPEAEFARQGLpskDEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHKEnGAVITRSSqpl 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246  279 -GfyIASDPNKEDIRAVESMLQAGHSD----VVLV------------------ETMDEMPSladIQLAHL---------- 325
Cdd:pfam06602  89 vG--LNGKRSIEDEKLLQAIFKSSNPYsakkLYIVdarpklnamanrakgggyENEDNYPN---CKKIFLgienihvmrd 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246  326 ---KLRALCLpDSSVAEDKWLSALEGTRWLDYVRSCLRKASDI---------SVLV--------TSRVRSVVlQELGDrd 385
Cdd:pfam06602 164 slnKLVEACN-DRSPSMDKWLSRLESSGWLKHIKAILDGACLIaqavdlegsSVLVhcsdgwdrTAQLTSLA-QLLLD-- 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246  386 fngllsslvqlllaPEARTLFGFQSLVQREWVAAGHPFLTRLG----DTGASEEAPVFPLFLDCAWQLLQQFPAEFEFSE 461
Cdd:pfam06602 240 --------------PYYRTIEGFQVLIEKEWLSFGHKFADRCGhlagFTDSKERSPVFLQFLDCVWQLLRQFPCAFEFNE 305


                  ....*...
gi 224994246  462 FFLLALHD 469
Cdd:pfam06602 306 RFLIRLLY 313
3-PAP pfam12578
Myotubularin-associated protein; This domain family is found in eukaryotes, and is typically ...
 549-683 4.22e-26

Myotubularin-associated protein; This domain family is found in eukaryotes, and is typically between 115 and 138 amino acids in length. Myotubularin is a dual-specific phosphatase that dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol (3,5)-bisphosphate. 3-PAP is a catalytically inactive member of the myotubularin gene family, which coprecipitates lipid phosphatidylinositol 3-phosphate-3-phosphatase activity from lysates of human platelets.


Pssm-ID: 463634  Cd Length: 132  Bit Score: 103.99  E-value: 4.22e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246  549 RFSRQQQSLMVPGPPSSMwlfsrGTLTPLNQLCPWQDSSSLLAVSSHWLPrpARSSESlaDQEWGLPSHWGACPLPPGLL 628
Cdd:pfam12578   1 KRRKKSYSSTLRGPPPSL-----KNGLFRDEEDLLRRNSLLLRLKPDCPL--HRSSDS--NDSEQFFRDWFSKPADLHGL 71

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 224994246  629 -LPGYLGPQIRFWKRCYLRGRPEVQMGSSAL-----TVSALQDELSHLQELLRQWTPRISP 683
Cdd:pfam12578  72 lLPLLSGPHIKLWKLCYLRWVPEAQINHGGPitafhKLSLLADEVEALQRLLRQYRGGPSE 132
 
Name Accession Description Interval E-value
PTP-MTMR11 cd14595
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 259-449 2.84e-102

protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related phosphoinositide phosphatase 11; Myotubularin related phosphoinositide phosphatase 11 (MTMR11), also called cisplatin resistance-associated protein (hCRA) in humans, is enzymatically inactive and contains a C-terminal coiled-coil domain and an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. MTMR11 is a pseudophosphatase that lacks the catalytic cysteine in its catalytic pocket.


Pssm-ID: 350443  Cd Length: 195  Bit Score: 310.99  E-value: 2.84e-102
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 259 GRGPRLSWHHPGGSDLLRCGGFYIASDPNKEDIRAVESMLQAGHSDVVLVETMDEMPSLADIQLAHLKLRALCLPDSSVA 338
Cdd:cd14595    1 GRIPRWCWHHPGGSDLLRMAGFYTNSDPEKEDIRSVELLLQAGHSQCVIVDTSEELPSPADIQLAYLKLRTLCLPDISVS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 339 ED--KWLSALEGTRWLDYVRSCLRKASDISVLVTSRVRSVVLQELGDRDFNGLLSSLVQLLLAPEARTLFGFQSLVQREW 416
Cdd:cd14595   81 VSdeKWLSNLEGTRWLDHVRACLRKASEVSCLLAERHRSVILQESEDRDLNCLLSSLVQLLSDPHARTISGFQSLVQKEW 160

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 224994246 417 VAAGHPFLTRLGDTG--ASEEAPVFPLFLDCAWQL 449
Cdd:cd14595  161 VVAGHPFLQRLNLTResDKEESPVFLLFLDCVWQL 195
PTP-MTMR10-like cd14537
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 259-448 2.62e-69

protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related phosphoinositide phosphatases 10, 11, and 12; This subgroup of enzymatically inactive phosphatase domains of myotubularins consists of MTMR10, MTMR11, MTMR12, and similar proteins. Beside the phosphatase domain, they contain an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. MTMR10, MTMR11, and MTMR12 are pseudophosphatases that lack the catalytic cysteine in their catalytic pocket. MTMR12 functions as an adapter for the catalytically active myotubularin to regulate its intracellular location.


Pssm-ID: 350385  Cd Length: 200  Bit Score: 224.91  E-value: 2.62e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 259 GRGPRLSWHHPGGSDLLRCGGFYiasdpNKEDIRAVESMLQ-------AGHSDVVLVETMDEMPSLADIQLAHLKLRALC 331
Cdd:cd14537    1 GRPPVWCWSHPNGAALVRMAELL-----PTITDRTQENKMLeairkshPNLKKPKVIDLDKLLPSLQDVQAAYLKLRELC 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 332 LPDSSVAED----KWLSALEGTRWLDYVRSCLRKASDISVLVTSRVRSVVLQELGDRDFNGLLSSLVQLLLAPEARTLFG 407
Cdd:cd14537   76 TPDSSEQFWvqdsKWYSLLENTKWLHYVSACLKKASEAAEALESRGRSVVLQESDGRDLSCVVSSLVQLLLDPHFRTITG 155

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*
gi 224994246 408 FQSLVQREWVAAGHPFLTRLG----DTGASEEAPVFPLFLDCAWQ 448
Cdd:cd14537  156 FQSLIQKEWVALGHPFCDRLGhvkpNKTESEESPVFLLFLDCVWQ 200
PH-GRAM_MTMR11 cd15790
Myotubularian (MTM) related 11 protein (MTMR11) Pleckstrin Homology-Glucosyltransferases, ...
 51-165 1.89e-52

Myotubularian (MTM) related 11 protein (MTMR11) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR10, MTMR11, and MTMR12 are catalytically inactive phosphatases that play a role as an adapter for the phosphatase myotubularin to regulate myotubularintracellular location. They contains a Glu residue instead of a conserved Cys residue in the dsPTPase catalytic loop which renders it catalytically inactive as a phosphatase. They contains an N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an inactive PTP domain, a SET interaction domain, and a C-terminal coiled-coil 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: 275433  Cd Length: 123  Bit Score: 176.89  E-value: 1.89e-52
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246  51 LPGEHILAWAPGRRK------GPGlDLPGTLICTNFRVTFQPCGWQR---KQDTPLSSENDFALINIGRLEAVSGLSRVQ 121
Cdd:cd15790    1 LPGEHILEEAVRVRKlvqwrdGEG-FLSGTLYCTNFRVAFVPEHIQKdenDHDTVLNSEHDIALPSIDRVVAVQGPTTMK 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....
gi 224994246 122 LLRPGSQLKFIPEELLLHGRDFRLLRVGFEAGGLAPQAFQVTMA 165
Cdd:cd15790   80 AVTASSGLKFIPEELVIYCRDFRLLRFQFEQSTLEPQAFQITTA 123
PH-GRAM_MTMR10-like cd13212
Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins ...
 51-165 8.21e-50

Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR10, MTMR11, and MTMR12 are catalytically inactive phosphatases that play a role as an adapter for the phosphatase myotubularin to regulate myotubularintracellular location. They contains a Glu residue instead of a conserved Cys residue in the dsPTPase catalytic loop which renders it catalytically inactive as a phosphatase. They contains an N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an inactive PTP domain, a SET interaction domain, and a C-terminal coiled-coil 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: 275399  Cd Length: 125  Bit Score: 170.11  E-value: 8.21e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246  51 LPGEHILAWAPGRRKGPGLD-----LPGTLICTNFRVTFQPCGWQ----RKQDTPLSSENDFALINIGRLEAVSGLSRVQ 121
Cdd:cd13212    1 LPGEQVLAEAPGVRKGLQEDssqpeLSGTLICTNFKITFQPDDWQwldnTQQKNPLNGEYDFALVCIGQIEAVSDLKRVQ 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 224994246 122 LLRPGSQLKFIPEELLLHGRDFRLLRVGFEA-GGLAPQAFQVTMA 165
Cdd:cd13212   81 LLRPGSLLKFIPEELIIHCKDFRVLRFGFEAtGGEEPKAFQVTIA 125
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
 206-469 3.12e-46

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: 461958 [Multi-domain]  Cd Length: 332  Bit Score: 167.27  E-value: 3.12e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246  206 DWETECKKQGA---RGWRVSTVNERFDVATSLSGYFWVPNRILDSEVRRAFAHFHQGRGPRLSWHHPG-GSDLLRCG--- 278
Cdd:pfam06602   9 DPEAEFARQGLpskDEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHKEnGAVITRSSqpl 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246  279 -GfyIASDPNKEDIRAVESMLQAGHSD----VVLV------------------ETMDEMPSladIQLAHL---------- 325
Cdd:pfam06602  89 vG--LNGKRSIEDEKLLQAIFKSSNPYsakkLYIVdarpklnamanrakgggyENEDNYPN---CKKIFLgienihvmrd 163

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246  326 ---KLRALCLpDSSVAEDKWLSALEGTRWLDYVRSCLRKASDI---------SVLV--------TSRVRSVVlQELGDrd 385
Cdd:pfam06602 164 slnKLVEACN-DRSPSMDKWLSRLESSGWLKHIKAILDGACLIaqavdlegsSVLVhcsdgwdrTAQLTSLA-QLLLD-- 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246  386 fngllsslvqlllaPEARTLFGFQSLVQREWVAAGHPFLTRLG----DTGASEEAPVFPLFLDCAWQLLQQFPAEFEFSE 461
Cdd:pfam06602 240 --------------PYYRTIEGFQVLIEKEWLSFGHKFADRCGhlagFTDSKERSPVFLQFLDCVWQLLRQFPCAFEFNE 305


                  ....*...
gi 224994246  462 FFLLALHD 469
Cdd:pfam06602 306 RFLIRLLY 313
PTP-MTMR10 cd14593
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 259-448 7.81e-40

protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related phosphoinositide phosphatase 10; Myotubularin related phosphoinositide phosphatase 10 (MTMR10) is enzymatically inactive and contains an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. MTMR10 is a pseudophosphatase that lacks the catalytic cysteine in its catalytic pocket.


Pssm-ID: 350441  Cd Length: 195  Bit Score: 145.03  E-value: 7.81e-40
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 259 GRGPRLSWHHPGGSDLLRCGGFYIASDPNKEDIRAVESMLQAG--HSDVVLVETMDEMPSLADIQLAHLKLRALCLPDS- 335
Cdd:cd14593    1 RRIPLWCWNHPNGSALVRMANIKDLLQQRKIDQRICNAITRSHplRSDVYKSDLDKTLPNIQEIQAAFVKLKQLCVNEPf 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 336 SVAEDKWLSALEGTRWLDYVRSCLRKASDISVLVTSRVRSVVLQELGDRDFNGLLSSLVQLLLAPEARTLFGFQSLVQRE 415
Cdd:cd14593   81 EETEEKWLSSLESTRWLEYVRAFLKHSAELVYMLESKHVSVILQEEEGRDLSCVVASLVQVMLDPYFRTITGFQSLIQKE 160

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 224994246 416 WVAAGHPFLTRLGDTGAS--EEAPVFPLFLDCAWQ 448
Cdd:cd14593  161 WVMAGYRFLDRCNHLKKSskKESPLFLLFLDCVWQ 195
PTP-MTMR12 cd14594
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 262-449 5.26e-32

protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related phosphoinositide phosphatase 12; Myotubularin related phosphoinositide phosphatase 12 (MTMR12), also called phosphatidylinositol 3 phosphate 3-phosphatase adapter subunit (3-PAP), is enzymatically inactive and contains a C-terminal coiled-coil domain and an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. MTMR12 is a pseudophosphatase that lacks the catalytic cysteine in its catalytic pocket. It functions as an adapter for the catalytically active myotubularin to regulate its intracellular location.


Pssm-ID: 350442  Cd Length: 203  Bit Score: 123.41  E-value: 5.26e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 262 PRLSWHHPGGSDLLRCGGF-----YIASDPNKEDIRAVESMLQAGHSDVVLVETMDE-MPSLADIQLAHLKLRALCLPDS 335
Cdd:cd14594    4 PIWCWSCHNGCALLKMSALpkeqdDVALQDQKSFLDRIYKTLSRPPYESVKTEDLSAsLPSLQEIQTAYNRFKQLFLIDN 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 336 SV----AEDKWLSALEGTRWLDYVRSCLRKASDISVLVTSRVRSVVLQELGDRDFNGLLSSLVQLLLAPEARTLFGFQSL 411
Cdd:cd14594   84 STdfwdTDVKWFSSLESSNWLEIIRQCLKKAVEVVECLEKQNTNVLLTEEEATDLCCVISSLVQIMMDPYCRTKSGFQSL 163

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 224994246 412 VQREWVAAGHPFLTRLGDTGAS--EEAPVFPLFLDCAWQL 449
Cdd:cd14594  164 IQKEWVMGGHCFLDRCNHLRQNdkEEVPVFLLFLDCVWQL 203
PTP-MTMR6-like cd14532
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases ...
 207-471 5.88e-32

protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases 6, 7, and 8; This subgroup of enzymatically active phosphatase domains of myotubularins consists of MTMR6, MTMR7 and MTMR8, and related domains. Beside the phosphatase domain, they contain a C-terminal coiled-coil domain and an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively. MTMR6, MTMR7 and MTMR8 form complexes with catalytically inactive MTMR9, and display differential substrate preferences. In cells, the MTMR6/R9 complex significantly increases the cellular levels of PtdIns(5)P, the product of PI(3,5)P(2) dephosphorylation, whereas the MTMR8/R9 complex reduces cellular PtdIns(3)P levels. The MTMR6/R9 complex serves to inhibit stress-induced apoptosis while the MTMR8/R9 complex inhibits autophagy.


Pssm-ID: 350380 [Multi-domain]  Cd Length: 301  Bit Score: 125.92  E-value: 5.88e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 207 WETECKKQGA--RGWRVSTVNERFDVATSLSGYFWVPnRILDSEVRRAFAHFH-QGRGPRLSWHHPGG-SDLLRC----G 278
Cdd:cd14532    1 LESEYTRMGVpnDNWTLSDINKDYELCDTYPRELFVP-TSASTPVLVGSSKFRsKGRLPVLSYLHKDNqAAICRCsqplS 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 279 GFYIASDpnkEDiravESMLQA-----GHSDVVLV-------------------ETMDEMPSLA----DIQLAHL----- 325
Cdd:cd14532   80 GFSARCV---ED----EQLLQAirkanPNSKFMYVvdtrpkinamankaagkgyENEDNYSNIKfqffGIENIHVmrssl 152

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 326 -KLRALCLpDSSVAEDKWLSALEGTRWLDYVRSCLrkasDISVLVTSRVR---SVVLQELGDRDFNGLLSSLVQLLLAPE 401
Cdd:cd14532  153 qKLLEVCE-LKNPSMSAFLSGLESSGWLKHIKAVM----DTSVFIAKAVSegaSVLVHCSDGWDRTAQTCSLASLLLDPY 227

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 224994246 402 ARTLFGFQSLVQREWVAAGHPFLTRLG--DTGASEEAPVFPLFLDCAWQLLQQFPAEFEFSEFFLLALHDSI 471
Cdd:cd14532  228 YRTIKGFQVLIEKEWLSFGHKFTDRCGhlQGDAKEVSPVFTQFLDCVWQLMQQFPRAFEFNERFLLTLHDHV 299
PTP-MTMR2 cd14590
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 246-471 1.02e-28

protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase 2; Myotubularin related phosphoinositide phosphatase 2 (MTMR2) is enzymatically active and contains an additional N-terminal PH-GRAM domain and C-terminal coiled-coiled domain and PDZ binding site. Mutations in MTMR2 causes Charcot-Marie-Tooth type 4B1, a severe childhood-onset neuromuscular disorder, characterized by demyelination and redundant loops of myelin known as myelin outfoldings, a similar phenotype as mutations in MTMR13. MTMR13, an inactive phosphatase, is believed to interact with MTMR2 and stimulate its phosphatase activity. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively.


Pssm-ID: 350438  Cd Length: 262  Bit Score: 115.52  E-value: 1.02e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 246 DSEVRRAFAHFHQGRGPRLSWHHP-GGSDLLRCGGFYIASD--PNKEDIRAVESMLQA-GHSDVVLVetMDEMPSL---- 317
Cdd:cd14590    1 DEELKRVASFRSRGRIPVLSWIHPeSQATITRCSQPMVGVSgkRSKEDEKYLQAIMDSnAQSHKIFI--FDARPSVnava 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 318 ---------------------ADIQLAHL------KLRALCLPDssVAEDKWLSALEGTRWLDYVRSCLRKASDISVLVT 370
Cdd:cd14590   79 nkakgggyesedayqnaelvfLDIHNIHVmreslrKLKEIVYPN--IEESHWLSNLESTHWLEHIKLILAGALRIADKVE 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 371 SRVRSVVLQELGDRDFNGLLSSLVQLLLAPEARTLFGFQSLVQREWVAAGHPFLTRLG----DTGASEEAPVFPLFLDCA 446
Cdd:cd14590  157 SGKTSVVVHCSDGWDRTAQLTSLAMLMLDGYYRTIRGFEVLVEKEWLSFGHRFQLRVGhgdkNHADADRSPVFLQFIDCV 236

                        250       260
                 ....*....|....*....|....*
gi 224994246 447 WQLLQQFPAEFEFSEFFLLALHDSI 471
Cdd:cd14590  237 WQMTRQFPTAFEFNEYFLITILDHL 261
PTP-MTM1-like cd14535
protein tyrosine phosphatase-like domain of myotubularin, and myotubularin related ...
 259-469 8.12e-28

protein tyrosine phosphatase-like domain of myotubularin, and myotubularin related phosphoinositide phosphatases 1 and 2; This subgroup of enzymatically active phosphatase domains of myotubularins consists of MTM1, MTMR1 and MTMR2. All contain an additional N-terminal PH-GRAM domain and C-terminal coiled-coiled domain and PDZ binding site. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively.


Pssm-ID: 350383  Cd Length: 249  Bit Score: 112.54  E-value: 8.12e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 259 GRGPRLSWHHP-GGSDLLRCggfyiaSDP--------NKEDIRAVESMLQA-GHSDVVLVetMDEMPS------------ 316
Cdd:cd14535    1 NRIPVLSWIHPeSQATITRC------SQPlvgvsgkrSKDDEKYLQLIMDAnAQSHKLFI--MDARPSvnavankakggg 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 317 -------------LADIQLAHL------KLRALCLPdsSVAEDKWLSALEGTRWLDYVRSCLRKASDISVLVTSRVRSVV 377
Cdd:cd14535   73 yesedayqnaelvFLDIHNIHVmreslrKLKDICFP--NIDDSHWLSNLESTHWLEHIKLILAGAVRIADKVESGKTSVV 150

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 378 LQELGDRDFNGLLSSLVQLLLAPEARTLFGFQSLVQREWVAAGHPFLTRLG----DTGASEEAPVFPLFLDCAWQLLQQF 453
Cdd:cd14535  151 VHCSDGWDRTAQLTSLAMLMLDPYYRTIRGFEVLIEKEWLSFGHKFAQRIGhgdkNHSDADRSPVFLQFIDCVWQMTRQF 230

                        250
                 ....*....|....*.
gi 224994246 454 PAEFEFSEFFLLALHD 469
Cdd:cd14535  231 PNAFEFNEHFLITILD 246
PTP-MTMR1 cd14592
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 259-471 3.76e-27

protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase 1; Myotubularin-related phosphoinositide phosphatase 1 (MTMR1) is enzymatically active and contains an N-terminal PH-GRAM domain, a C-terminal coiled-coiled domain and a PDZ binding site. MTMR1 is associated with myotonic dystrophy. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively.


Pssm-ID: 350440  Cd Length: 249  Bit Score: 110.84  E-value: 3.76e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 259 GRGPRLSWHHP-GGSDLLRCGGFYIAsdPN----KEDIRAVESMLQAGHSDVVLVETMDEMPSLAD-------------- 319
Cdd:cd14592    1 GRVPVLSWIHPeSQATITRCSQPLVG--PNdkrcKEDEKYLQTIMDANAQSHKLIIFDARQNSVADtnktkgggyesesa 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 320 ----------IQLAHL------KLRALCLPdsSVAEDKWLSALEGTRWLDYVRSCLRKASDISVLVTSRVRSVVLQELGD 383
Cdd:cd14592   79 ypnaelvfleIHNIHVmreslrKLKEIVYP--SIDEARWLSNVDGTHWLEYIRMLLAGAVRIADKIESGKTSVVVHCSDG 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 384 RDFNGLLSSLVQLLLAPEARTLFGFQSLVQREWVAAGHPFLTRLG----DTGASEEAPVFPLFLDCAWQLLQQFPAEFEF 459
Cdd:cd14592  157 WDRTAQLTSLAMLMLDSYYRTIKGFEVLIEKEWISFGHRFALRVGhgddNHADADRSPIFLQFIDCVWQMTRQFPSAFEF 236

                        250
                 ....*....|..
gi 224994246 460 SEFFLLALHDSI 471
Cdd:cd14592  237 NELFLITILDHL 248
3-PAP pfam12578
Myotubularin-associated protein; This domain family is found in eukaryotes, and is typically ...
 549-683 4.22e-26

Myotubularin-associated protein; This domain family is found in eukaryotes, and is typically between 115 and 138 amino acids in length. Myotubularin is a dual-specific phosphatase that dephosphorylates phosphatidylinositol 3-phosphate and phosphatidylinositol (3,5)-bisphosphate. 3-PAP is a catalytically inactive member of the myotubularin gene family, which coprecipitates lipid phosphatidylinositol 3-phosphate-3-phosphatase activity from lysates of human platelets.


Pssm-ID: 463634  Cd Length: 132  Bit Score: 103.99  E-value: 4.22e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246  549 RFSRQQQSLMVPGPPSSMwlfsrGTLTPLNQLCPWQDSSSLLAVSSHWLPrpARSSESlaDQEWGLPSHWGACPLPPGLL 628
Cdd:pfam12578   1 KRRKKSYSSTLRGPPPSL-----KNGLFRDEEDLLRRNSLLLRLKPDCPL--HRSSDS--NDSEQFFRDWFSKPADLHGL 71

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 224994246  629 -LPGYLGPQIRFWKRCYLRGRPEVQMGSSAL-----TVSALQDELSHLQELLRQWTPRISP 683
Cdd:pfam12578  72 lLPLLSGPHIKLWKLCYLRWVPEAQINHGGPitafhKLSLLADEVEALQRLLRQYRGGPSE 132
PTP-MTM1 cd14591
protein tyrosine phosphatase-like domain of myotubularin phosphoinositide phosphatase 1; ...
 260-471 1.32e-25

protein tyrosine phosphatase-like domain of myotubularin phosphoinositide phosphatase 1; Myotubularin phosphoinositide phosphatase 1 (MTM1), also called myotubularin, is enzymatically active and contains an N-terminal PH-GRAM domain and C-terminal coiled-coiled domain and PDZ binding site. Mutations in MTM1 cause X-linked myotubular myopathy. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively.


Pssm-ID: 350439  Cd Length: 249  Bit Score: 106.27  E-value: 1.32e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 260 RGPRLSWHHP-GGSDLLRCGGFYI--ASDPNKEDIRAVESMLQAGHSDVVLVeTMDEMPSL------------------- 317
Cdd:cd14591    2 RIPVLSWIHPeNQAVIMRCSQPLVgmSGKRNKDDEKYLDIIREANGQTSKLT-IYDARPSVnavankatgggyegddayq 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 318 ------ADIQLAHL------KLRALCLPDssVAEDKWLSALEGTRWLDYVRSCLRKASDISVLVTSRVRSVVLQELGDRD 385
Cdd:cd14591   81 naelvfLDIHNIHVmreslkKLKDIVYPN--VEESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWD 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 386 FNGLLSSLVQLLLAPEARTLFGFQSLVQREWVAAGHPFLTRLG----DTGASEEAPVFPLFLDCAWQLLQQFPAEFEFSE 461
Cdd:cd14591  159 RTAQLTSLAMLMLDSYYRTIEGFEVLVQKEWISFGHKFASRIGhgdkNHADADRSPIFLQFIDCVWQMSKQFPTAFEFNE 238

                        250
                 ....*....|
gi 224994246 462 FFLLALHDSI 471
Cdd:cd14591  239 QFLITILDHL 248
PTP-MTM-like cd14507
protein tyrosine phosphatase-like domain of myotubularins; Myotubularins are a unique subgroup ...
 259-448 2.90e-24

protein tyrosine phosphatase-like domain of myotubularins; Myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively. Not all members are catalytically active proteins, some function as adaptors for the active members.


Pssm-ID: 350357  Cd Length: 226  Bit Score: 101.86  E-value: 2.90e-24
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 259 GRGPRLSWHHP-GGSDLLRCGGFY--IASDPNKEDIRAVESMLQAGHSDVVLVeTMDEMPSLA----------------- 318
Cdd:cd14507    1 GRIPVLSWRHPrNGAVICRSSQPLvgLTGSRSKEDEKLLNAIRKASPSSKKLY-IVDARPKLNavanrakgggyenteyy 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 319 -DIQLAHL-------------KLRALCLPDSSVaEDKWLSALEGTRWLDYVRSCLRKASDI---------SVLV------ 369
Cdd:cd14507   80 pNCELEFLnienihamrdslnKLRDACLSPNDE-ESNWLSALESSGWLEHIRLILKGAVRVadllekegtSVLVhcsdgw 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 370 --TSRVRSVVlQELGDrdfngllsslvqlllaPEARTLFGFQSLVQREWVAAGHPFLTRLG----DTGASEEAPVFPLFL 443
Cdd:cd14507  159 drTSQLTSLA-QLLLD----------------PYYRTIEGFQVLIEKEWLSFGHKFADRCGhgdkNSSDEERSPIFLQFL 221


                 ....*
gi 224994246 444 DCAWQ 448
Cdd:cd14507  222 DCVWQ 226
PTP-MTMR8 cd14584
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 219-471 6.03e-21

protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase 8; Myotubularin related phosphoinositide phosphatase 8 (MTMR8) is enzymatically active and contains a C-terminal coiled-coil domain and an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively. MTMR8 forms a complex with catalytically inactive MTMR9 and preferentially dephosphorylates PtdIns(3)P; the MTMR8/R9 complex inhibits autophagy. In zebrafish, it cooperates with PI3K to regulate actin filament modeling and muscle development.


Pssm-ID: 350432 [Multi-domain]  Cd Length: 308  Bit Score: 94.17  E-value: 6.03e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 219 WRVSTVNERFDVATSLSGYFWVPNRILDSEVRRAFAHFHQGRGPRLSWHHP-GGSDLLRCG----GFYIASdpnKEDira 293
Cdd:cd14584   21 WEITDANKNYEICSTYPPELVVPKSASKATVVGSSKFRSRGRFPVLSYLYKeNNAAICRCSqplsGFSARC---VED--- 94

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 294 vESMLQA------GHSDVVLVETMDEMPSLAD----------------------IQLAHL------KLRALCLPDSSVAE 339
Cdd:cd14584   95 -EQMLQAiskanpGSPFMYVVDTRPKLNAMANraagkgyenednysnirfqfigIENIHVmrsslqKLLEVCEMKSPSMS 173

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 340 DkWLSALEGTRWLDYVRSCLRKASDISVLVTSRVRSVVLQELGDRDFNGLLSSLVQLLLAPEARTLFGFQSLVQREWVAA 419
Cdd:cd14584  174 D-FLTGLENSGWLRHIKAVMDAGVFLAKAVKEEKASVLVHCSDGWDRTAQVCSLASLLLDPFYRTIKGLMVLIEKEWISM 252

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 224994246 420 GHPFLTRLG--DTGASEEAPVFPLFLDCAWQLLQQFPAEFEFSEFFLLALHDSI 471
Cdd:cd14584  253 GHKFSQRCGhlDGDPKEVSPVFTQFLECVWQLMEQFPCAFEFNEHFLLEIHDHV 306
PTP-MTMR5-like cd14534
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 219-452 6.84e-21

protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related phosphoinositide phosphatases 5 and 13; This subgroup of enzymatically inactive phosphatase domains of myotubularins consists of MTMR5, also known as SET binding factor 1 (SBF1) and MTMR13, also known as SET binding factor 2 (SBF2), and similar domains. Beside the pseudophosphatase domain, they contain a variety of other domains, including a DENN and a PH-like domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. MTMR5 and MTMR13 are pseudophosphatases that lack the catalytic cysteine in their catalytic pocket. Mutations in MTMR13 causes Charcot-Marie-Tooth type 4B2, a severe childhood-onset neuromuscular disorder, characterized by demyelination and redundant loops of myelin known as myelin outfoldings, a similar phenotype as mutations in MTMR2. Mutations in the MTMR5 gene cause Charcot-Marie-tooth disease type 4B3. MTMR5 and MTMR13 interact with MTMR2 and stimulate its phosphatase activity.


Pssm-ID: 350382 [Multi-domain]  Cd Length: 274  Bit Score: 93.20  E-value: 6.84e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 219 WRVSTVNERFDVATSLSGYFWVPNRILDSEVRRAFAHFHQGRGPRLSWHHPG-GSDLLRCGGFYIAS------------- 284
Cdd:cd14534    1 FRISTANRDYSICRSYPALVVVPQSVSDESLRKVARCYRQGRFPVVTWRHPRtKALLLRSGGFHGKGvmgmlksantsts 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 285 ---DPNKEDIRAVESM--LQA---------GHSDVVLVET-------MDEMPSLADIQLAHLKLRALCLPDSSVAEDK-- 341
Cdd:cd14534   81 sptVSSSETSSSLEQEkyLSAlvlyvlgekSQMKGVKAESdpkcefiPVEYPEVRQVKASFKKLLRACVPSSAPTEPEqs 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 342 WLSALEGTRWLDYVRSCLRKASDISVLVTSRVRSVVLQELGDRDFNGLLSSLVQLLLAPEARTLFGFQSLVQREWVAAGH 421
Cdd:cd14534  161 FLKAVEDSEWLQQLQCLMQLSGAVVDLLDVQGSSVLLCLEDGWDVTTQVSSLSQLLLDPYYRTLEGFRVLVEKEWLAFGH 240

                        250       260       270
                 ....*....|....*....|....*....|....
gi 224994246 422 PFLTRLGDTGASEE---APVFPLFLDCAWQLLQQ 452
Cdd:cd14534  241 RFSHRSNLTAASQSsgfAPVFLQFLDAVHQIHRQ 274
PTP-MTMR6 cd14585
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 219-471 1.95e-20

protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase 6; Myotubularin related phosphoinositide phosphatase 6 is enzymatically active and contains a C-terminal coiled-coil domain and an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively. MTMR6 forms a complex with catalytically inactive MTMR9 and preferentially dephosphorylates PtdIns(3,5)P(2); the MTMR6/R9 complex serves to inhibit stress-induced apoptosis.


Pssm-ID: 350433 [Multi-domain]  Cd Length: 302  Bit Score: 92.30  E-value: 1.95e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 219 WRVSTVNERFDVATSLSGYFWVPnRILDSEVRRAFAHFH-QGRGPRLSWHHPGG-SDLLRCG----GFyiaSDPNKEDIR 292
Cdd:cd14585   15 WQLSDVNRDYKICDTYPRDLYVP-ITASKPIIVGSSKFRsKGRFPVLSYYHQEKkAAICRCSqplsGF---SARCLEDEH 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 293 AVESMLQAGHSDVvLVETMDEMPSL-------------------------ADIQLAHL------KLRALCLPDSSVAEDk 341
Cdd:cd14585   91 MLQAISKANPNNR-YMYVMDTRPKLnamanraagkgyenednysnirfqfVGIENIHVmrsslqKLLEVCGTKALSVND- 168

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 342 WLSALEGTRWLDYVRSCLRKASDISVLVTSRVRSVVLQELGDRDFNGLLSSLVQLLLAPEARTLFGFQSLVQREWVAAGH 421
Cdd:cd14585  169 FLSGLESSGWLRHIKAVLDAAVFLAKAVAVEGASVLVHCSDGWDRTAQVCSLGSLLLDPYYRTIKGFMVLIEKDWISFGH 248

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 224994246 422 PFLTRLG--DTGASEEAPVFPLFLDCAWQLLQQFPAEFEFSEFFLLALHDSI 471
Cdd:cd14585  249 KFSDRCGqlDGDPKEISPVFTQFLECVWQLTEQFPRAFEFSEAFLLQIHEHI 300
PTP-MTMR9 cd14536
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 259-448 2.08e-19

protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related phosphoinositide phosphatase 9; Myotubularin related phosphoinositide phosphatase 9 (MTMR9) is enzymatically inactive and contains a C-terminal coiled-coil domain and an N-terminal PH-GRAM domain. Mutations have been associated with obesity and metabolic syndrome. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. MTMR9 is a pseudophosphatase that lacks the catalytic cysteine in its catalytic pocket. It forms complexes with catalytically active MTMR6, MTMR7 and MTMR8, and regulates their activities; the complexes display differential substrate preferences. The MTMR6/R9 complex serves to inhibit stress-induced apoptosis while the MTMR8/R9 complex inhibits autophagy.


Pssm-ID: 350384  Cd Length: 224  Bit Score: 87.39  E-value: 2.08e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 259 GRGPRLSW-HHPGGSDLLRCGgfYIASDPN----KEDIRAVESMLQAGHSDVVL-----------------VETMDEMPS 316
Cdd:cd14536    1 GRFPVLSYyHKKNGMVLMRSS--QPLTGPNgkrcKEDEKLLNAVLGGGKRGYIIdtrsknvaqqarakgggFEPEAHYPQ 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 317 LADIQLAHLKLRAL----------CLpDSSVAEDKWLSALEGTRWLDYVRSCLRKA---------SDISVLV-------- 369
Cdd:cd14536   79 WRRIHKPIERYNVLqesliklveaCN-DQGHSMDKWLSKLESSNWLSHVKEILTTAclvaqcidrEGASVLVhgsegmds 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 370 TSRVRSVVlQELGDrdfngllsslvqlllaPEARTLFGFQSLVQREWVAAGHPFLTR-----LGDTGASEEAPVFPLFLD 444
Cdd:cd14536  158 TLQVTSLA-QIILD----------------PDCRTIRGFEALIEREWLQAGHPFQSRcaksaYSNSKQKFESPVFLLFLD 220


                 ....
gi 224994246 445 CAWQ 448
Cdd:cd14536  221 CVWQ 224
PTP-MTMR7 cd14583
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 219-471 2.00e-18

protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase 7; Myotubularin related phosphoinositide phosphatase 7 (MTMR7) is enzymatically active and contains a C-terminal coiled-coil domain and an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively. In neuronal cells, MTMR7 forms a complex with catalytically inactive MTMR9 and dephosphorylates phosphatidylinositol 3-phosphate and Ins(1,3)P2.


Pssm-ID: 350431 [Multi-domain]  Cd Length: 302  Bit Score: 86.55  E-value: 2.00e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 219 WRVSTVNERFDVATSLSGYFWVPNRILDSEVRRAFAHFHQGRGPRLSWH-HPGGSDLLRCG----GFyiaSDPNKEDira 293
Cdd:cd14583   15 WQVSDVNRDYRVCDTYPTELYVPKSATAPIIVGSSKFRSRGRFPVLSYYcKDNNASICRSSqplsGF---SARCLED--- 88

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 294 vESMLQA------GHSDVVLVETMDEMPSLAD----------------------IQLAHL------KLRALC-LPDSSVA 338
Cdd:cd14583   89 -EQMLQAirkanpGSDFMYVVDTRPKLNAMANraagkgyenednysnikfqfigIENIHVmrnslqKMLEVCeLRSPSMG 167

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 339 EDKWlsALEGTRWLDYVRSCLRKASDISVLVTSRVRSVVLQELGDRDFNGLLSSLVQLLLAPEARTLFGFQSLVQREWVA 418
Cdd:cd14583  168 DFLW--GLENSGWLKHIKAIMDAGIFIAKAVAEEGASVLVHCSDGWDRTAQVCSVASLLLDPYYRTIKGFMVLIEKDWVS 245

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 224994246 419 AGHPFLTRLG--DTGASEEAPVFPLFLDCAWQLLQQFPAEFEFSEFFLLALHDSI 471
Cdd:cd14583  246 FGHKFNHRYGhlDGDPKEVSPVIDQFIECVWQLMEQFPCAFEFNERFLIHIHHHI 300
PTP-MTMR3-like cd14533
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases ...
 308-448 1.84e-14

protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases 3 and 4; This subgroup of enzymatically active phosphatase domains of myotubularins consists of MTMR3, also known as ZFYVE10, and MTMR4, also known as ZFYVE11, and related domains. Beside the phosphatase domain, they contain a C-terminal FYVE domain and an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively.


Pssm-ID: 350381  Cd Length: 229  Bit Score: 73.21  E-value: 1.84e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 308 VETMDeMPSLADIQLAHLKLRALClpDSSVAEDKWLSALEGTRWLDYVRSCLRKASDISVLVTSRVRSVVLQELGDRDFN 387
Cdd:cd14533   88 VVFMN-LANIHAIRKSFHSLRALC--SSAPDQPNWLSNLESTKWLHHLSGLLKAALLVVNAVDEEGRPVLVHCSDGWDRT 164

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 224994246 388 GLLSSLVQLLLAPEARTLFGFQSLVQREWVAAGHPFLTRLGDTGASEEA----PVFPLFLDCAWQ 448
Cdd:cd14533  165 PQIVALAELMLDPYYRTIEGFQVLVEREWLDFGHKFADRCGHGVNSEDInercPVFLQWLDCVHQ 229
PTP-MTMR4 cd14587
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 314-448 6.29e-14

protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase 4; Myotubularin related phosphoinositide phosphatase 4 (MTMR4), also known as FYVE domain-containing dual specificity protein phosphatase 2 (FYVE-DSP2) or zinc finger FYVE domain-containing protein 11 (ZFYVE11), is enzymatically active and contains a C-terminal FYVE domain and an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively. MTMR4 localizes at the interface of early and recycling endosomes to regulate trafficking through this pathway. It plays a role in bacterial pathogenesis by stabilizing the integrity of bacteria-containing vacuoles.


Pssm-ID: 350435 [Multi-domain]  Cd Length: 308  Bit Score: 73.14  E-value: 6.29e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 314 MPSLADIQLAHLKLRALC--LPDSSvaedKWLSALEGTRWLDYVRSCLRKASDISVLVTSRVRSVVLQELGDRDFNGLLS 391
Cdd:cd14587  172 MANIHSIRNSFQYLRAVCsqMPDPG----NWLSALESTKWLQHLSVMLKAAVLVASAVDREGRPVLVHCSDGWDRTPQIV 247

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 224994246 392 SLVQLLLAPEARTLFGFQSLVQREWVAAGHPFLTRLGDT----GASEEAPVFPLFLDCAWQ 448
Cdd:cd14587  248 ALAKILLDPYYRTIEGFQVLVETDWLDFGHKFGDRCGHQenveDQNEQCPVFLQWLDCVHQ 308
PTP-MTMR5 cd14588
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 219-452 1.74e-13

protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related phosphoinositide phosphatase 5; Myotubularin related phosphoinositide phosphatase 5 (MTMR5), also known as SET binding factor 1 (SBF1), is enzymatically inactive and contains a variety of other domains, including a DENN and a PH-like domain. Mutations in the MTMR5 gene cause Charcot-Marie-tooth disease type 4B3. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. MTMR5 is a pseudophosphatase that lacks the catalytic cysteine in its catalytic pocket. It interacts with MTMR2, an active myotubularin related phosphatidylinositol phosphatase, regulates its enzymatic activity and subcellular location.


Pssm-ID: 350436 [Multi-domain]  Cd Length: 291  Bit Score: 71.54  E-value: 1.74e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 219 WRVSTVNERFDVATSLSGYFWVPNRILDSEVRRAFAHFHQGRGPRLSWHHP-GGSDLLRCGGFY-------------IAS 284
Cdd:cd14588    1 FRISTVNRMYAVCRSYPGLLIVPQSIQDNTIQRISRCYRQNRFPVVCWRNSrTKAVLLRSGGLHgkgvvglfksqnaPAA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 285 DPNKEDIRAVE-------------------------------------SMLQAGHSD------VVLVETMDempsLADIQ 321
Cdd:cd14588   81 GQSQTDSTSLEqekylqavinsmpryadasgrntlsgfraalyiigdkSQLKGVKQDplqqweVVPIEVFD----VRQVK 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 322 LAHLKLRALCLPD--SSVAEDKWLSALEGTRWLdyvrSCLRKASDISVLVTSRVR--SVVLQELGDR-DFNGLLSSLVQL 396
Cdd:cd14588  157 ASFKKLMKACVPScpSTDPSQTYLRTLEESEWL----SQLHKLLQVSVLVVELLDsgSSVLVSLEDGwDITTQVVSLVQL 232

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 224994246 397 LLAPEARTLFGFQSLVQREWVAAGHPFLTRLGDTGASEE---APVFPLFLDCAWQLLQQ 452
Cdd:cd14588  233 LSDPYYRTIEGFRLLVEKEWLSFGHRFSHRGAQTLASQSsgfTPVFLQFLDCVHQIHLQ 291
PTP-MTMR3 cd14586
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 219-448 1.39e-12

protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase 3; Myotubularin related phosphoinositide phosphatase 3 (MTMR3), also known as FYVE domain-containing dual specificity protein phosphatase 1 (FYVE-DSP1) or Zinc finger FYVE domain-containing protein 10 (ZFYVE10), is enzymatically active and contains a C-terminal FYVE domain and an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively. Together with phosphoinositide 5-kinase PIKfyve, phosphoinositide 3-phosphatase MTMR3 constitutes a phosphoinositide loop that produces PI(5)P via PI(3,5)P2 and regulates cell migration.


Pssm-ID: 350434  Cd Length: 317  Bit Score: 69.28  E-value: 1.39e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 219 WRVSTVNERFDVATSLSGYFWVPNRILDSEVRRAFAHFHQGRGPRLSWHHPG-GSDLLRCG-------GFYIASD----- 285
Cdd:cd14586    8 WRISNINEKYKLCGSYPQELIVPAWITDKELESVASFRSWKRIPAVVYRHQSnGAVIARCGqpevswwGWRNADDehlvq 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 286 --------------------------PNKEDIRAVE---SMLQAGHSDVVLVE-----TMDE------------------ 313
Cdd:cd14586   88 svakacasdssscksvlmtgncsrdfPNGGDLSDVEfdsSMSNASGVESLAIQpqkllILDArsyaaavanrakgggcec 167

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 314 -------------MPSLADIQLAHLKLRALC--LPDSSvaedKWLSALEGTRWLDYVrSCLRKASDISVLVTSRVRSVVL 378
Cdd:cd14586  168 peyypncevvfmgMANIHSIRKSFQSLRLLCtqMPDPA----NWLSALESTKWLQHL-SMLLKSALLVVHAVDRDQRPVL 242

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 224994246 379 QELGDR-DFNGLLSSLVQLLLAPEARTLFGFQSLVQREWVAAGHPFLTRLGDTGASEE----APVFPLFLDCAWQ 448
Cdd:cd14586  243 VHCSDGwDRTPQIVALSKLLLDPYYRTIEGFQVLVETEWLDFGHKFADRCGHGENSDDlnerCPVFLQWLDCVHQ 317
PH-GRAM_MTMR10 cd13346
Myotubularian (MTM) related 10 protein (MTMR10) Pleckstrin Homology-Glucosyltransferases, ...
 32-166 4.16e-12

Myotubularian (MTM) related 10 protein (MTMR10) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR10 is a catalytically inactive phosphatase that plays a role as an adapter for the phosphatase myotubularin to regulate myotubularintracellular location. It contains a Glu residue instead of a conserved Cys residue in the dsPTPase catalytic loop which renders it catalytically inactive as a phosphatase. MTMR10 contains an N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an inactive PTP domain, and a SET interaction 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: 270154  Cd Length: 177  Bit Score: 65.34  E-value: 4.16e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246  32 NRMPEPSSHQLGSCLasgcLPGEHILAWAPGRRKGPGLD-----LPGTLICTNFRVTF---QPCGWQRKQDTP-LSSEND 102
Cdd:cd13346    4 KINSEPKIKKLEPVL----LPGEIVVNEVNFVRKCIATDtsqydLWGKLICTNFKISFitdDPMPLQKFHYKNlLLGEHD 79

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 224994246 103 FALINIGRLEAVSGLSRVQ-LLRPGSQLKFIPEELLLHGRDFRLLRVGFEAGGlaPQ-AFQVTMAI 166
Cdd:cd13346   80 VPLTCIEQIVTVNDTKRKQkVLGPNQKLKFNPTELIIYCKDFRIVRFRFDEAG--PEsAKKVCLAI 143
PTP-MTMR13 cd14589
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 219-452 4.16e-12

protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related phosphoinositide phosphatase 13; Myotubularin related phosphoinositide phosphatase 13 (MTMR13), also known as SET binding factor 2 (SBF2), is enzymatically inactive and contains a variety of other domains, including a DENN and a PH-like domain. Mutations in MTMR13 causes Charcot-Marie-Tooth type 4B2, a severe childhood-onset neuromuscular disorder, characterized by demyelination and redundant loops of myelin known as myelin outfoldings, a similar phenotype as mutations in MTMR2. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. MTMR13 is a pseudophosphatase that lacks the catalytic cysteine in its catalytic pocket. It is believed to interact with MTMR2 and stimulate its phosphatase activity. It is also a guanine nucleotide exchange factor (GEF) which may activate RAB28, promoting the exchange of GDP to GTP and converting inactive GDP-bound Rab proteins into their active GTP-bound form.


Pssm-ID: 350437  Cd Length: 297  Bit Score: 67.64  E-value: 4.16e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 219 WRVSTVNERFDVATSLSGYFWVPNRILDSEVRRAFAHFHQGRGPRLSWHHP-GGSDLLRCGGFY--------------IA 283
Cdd:cd14589    1 FRITAVNRMYSLCRSYPGLLVVPQSVQDSSLQKVARCYRHNRLPVVCWKNSkTKAVLLRSGGFHgkgvvglfksqnphSA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 284 SDPNKEDIRAVES--MLQAGHSDVVLVETMDEMPSLADIQL-------------AHL----------------------- 325
Cdd:cd14589   81 APASSESSSSIEQekYLQALLNAISVHQKMNGNSTLLQSQLlkrqaalyifgekSQLrgfkldfalncefvpvefhdirq 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246 326 ------KLRALCLPDS--SVAEDKWLSALEGTRWLDYVRSCLRKASDISVLVTSRVRSVVLQELGdRDFNGLLSSLVQLL 397
Cdd:cd14589  161 vkasfkKLMRACVPSTipTDSEVTFLKALGESEWFLQLHRIMQLAVVISELLESGSSVMVCLEDG-WDITTQVVSLVQLL 239

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 224994246 398 LAPEARTLFGFQSLVQREWVAAGHPFLTRLGDTGASEE---APVFPLFLDCAWQLLQQ 452
Cdd:cd14589  240 SDPFYRTLEGFQMLVEKEWLSFGHKFSQRSNLTPNSQGsgfAPIFLQFLDCVHQIHNQ 297
PTP-MTM-like_fungal cd17666
protein tyrosine phosphatase-like domain of fungal myotubularins; Myotubularins are a unique ...
 400-448 1.29e-09

protein tyrosine phosphatase-like domain of fungal myotubularins; Myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively. Not all members are catalytically active proteins, some function as adaptors for the active members.


Pssm-ID: 350504  Cd Length: 229  Bit Score: 58.99  E-value: 1.29e-09
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 224994246 400 PEARTLFGFQSLVQREWVAAGHPFLTRLGDtgaSEEAPVFPLFLDCAWQ 448
Cdd:cd17666  184 PYYRTLEGFMVLVEKDWLSFGHRFAERSGH---KETSPVFHQFLDCVYQ 229
PH-GRAM_MTMR12 cd13348
Myotubularian (MTM) related 12 protein (MTMR12) Pleckstrin Homology-Glucosyltransferases, ...
 51-145 6.72e-04

Myotubularian (MTM) related 12 protein (MTMR12) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR12 is a catalytically inactive phosphatase that plays a role as an adapter for the phosphatase myotubularin to regulate myotubularintracellular location. It contains a Glu residue instead of a conserved Cys residue in the dsPTPase catalytic loop which renders it catalytically inactive as a phosphatase. MTMR12 contains an N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an inactive PTP domain, a SET interaction domain, and a C-terminal a coiled-coil 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: 275418  Cd Length: 178  Bit Score: 40.99  E-value: 6.72e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 224994246  51 LPGEHILAWAPGRRKGPGLDLP-----GTLICTNFRVTFqpCGWQRKQDT-------PLSSENDFALINIGRLEAVSGLS 118
Cdd:cd13348   21 LPGEVVLCEANTVLKYTQDDGSqrgvyGRLVCTNFRIAF--LGDDAPQDDnskqfknKIYGENDITLQCVDQIYGVYDEK 98

                         90       100
                 ....*....|....*....|....*..
gi 224994246 119 RvQLLRPGSQLKFIPEELLLHGRDFRL 145
Cdd:cd13348   99 K-KLITGGLVKNKYPEKLIIHCKDLRV 124
 
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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