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Conserved domains on  [gi|661567379|ref|NP_001281272|]
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myotubularin-related protein 12 isoform 2 [Homo sapiens]

Protein Classification

PTP-MTMR12 and 3-PAP domain-containing protein( domain architecture ID 13117803)

protein containing domains PH-like, PTP-MTMR12, and 3-PAP

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PTP-MTMR12 cd14594
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 260-462 1.14e-144

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: 420.02  E-value: 1.14e-144
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 260 HGIPIWCWSCHNGSALLKMSALPKEQDDGILQIQKSFLDGIYKTIHRPPYEIVKTEDLSSNFLSLQEIQTAYSKFKQLFL 339
Cdd:cd14594    1 RGIPIWCWSCHNGCALLKMSALPKEQDDVALQDQKSFLDRIYKTLSRPPYESVKTEDLSASLPSLQEIQTAYNRFKQLFL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 340 IDNSTEFWDTDIKWFSLLESSSWLDIIRRCLKKAIEITECMEAQNMNVLLLEENASDLCCLISSLVQLMMDPHCRTRIGF 419
Cdd:cd14594   81 IDNSTDFWDTDVKWFSSLESSNWLEIIRQCLKKAVEVVECLEKQNTNVLLTEEEATDLCCVISSLVQIMMDPYCRTKSGF 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 661567379 420 QSLIQKEWVMGGHCFLDRCNHLRQNDKEEVPVFLLFLDCVWQL 462
Cdd:cd14594  161 QSLIQKEWVMGGHCFLDRCNHLRQNDKEEVPVFLLFLDCVWQL 203
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
 26-202 2.29e-108

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 cd13348:

Pssm-ID: 473070  Cd Length: 178  Bit Score: 325.66  E-value: 2.29e-108
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379  26 PEEIHTNEKEVTEKEVTLHLLPGEQLLCEASTVLKYVQEDSCQHGVYGRLVCTDFKIAFLGDDESALDNDeTQFKNKVIG 105
Cdd:cd13348    1 TEEEIKLEKEPQEKEVNPHLLPGEVVLCEANTVLKYTQDDGSQRGVYGRLVCTNFRIAFLGDDAPQDDNS-KQFKNKIYG 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 106 ENDITLHCVDQIYGVFDEKKKTLFGQL--KKYPEKLIIHCKDLRVFQFCLRYTKEEEVKRIVSGIIHHTQAPKLLKRLFL 183
Cdd:cd13348   80 ENDITLQCVDQIYGVYDEKKKLITGGLvkNKYPEKLIIHCKDLRVFQFCLRYTKEEEVKRIVSGIIHHTQEPKLLKRLFL 159

                        170
                 ....*....|....*....
gi 661567379 184 FSYATAAQNNTVTDPKNHT 202
Cdd:cd13348  160 FSYARAAPNNTVTKREAIM 178
3-PAP pfam12578
Myotubularin-associated protein; This domain family is found in eukaryotes, and is typically ...
 505-633 1.93e-49

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: 169.08  E-value: 1.93e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379  505 HQRQLSLPLTQSKSSP--KRGFFREETDHLIKNLLGKRISK---LINSSDELQdnFREFYDSWHSKSTDYHGLLLPHIEG 579
Cdd:pfam12578   1 KRRKKSYSSTLRGPPPslKNGLFRDEEDLLRRNSLLLRLKPdcpLHRSSDSND--SEQFFRDWFSKPADLHGLLLPLLSG 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 661567379  580 PEIKVWAQRYLRWIPEAQILGGGQVATLSKLLEMMEEVQSLQEKIDERHHSQQA 633
Cdd:pfam12578  79 PHIKLWKLCYLRWVPEAQINHGGPITAFHKLSLLADEVEALQRLLRQYRGGPSE 132
 
Name Accession Description Interval E-value
PTP-MTMR12 cd14594
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 260-462 1.14e-144

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: 420.02  E-value: 1.14e-144
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 260 HGIPIWCWSCHNGSALLKMSALPKEQDDGILQIQKSFLDGIYKTIHRPPYEIVKTEDLSSNFLSLQEIQTAYSKFKQLFL 339
Cdd:cd14594    1 RGIPIWCWSCHNGCALLKMSALPKEQDDVALQDQKSFLDRIYKTLSRPPYESVKTEDLSASLPSLQEIQTAYNRFKQLFL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 340 IDNSTEFWDTDIKWFSLLESSSWLDIIRRCLKKAIEITECMEAQNMNVLLLEENASDLCCLISSLVQLMMDPHCRTRIGF 419
Cdd:cd14594   81 IDNSTDFWDTDVKWFSSLESSNWLEIIRQCLKKAVEVVECLEKQNTNVLLTEEEATDLCCVISSLVQIMMDPYCRTKSGF 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 661567379 420 QSLIQKEWVMGGHCFLDRCNHLRQNDKEEVPVFLLFLDCVWQL 462
Cdd:cd14594  161 QSLIQKEWVMGGHCFLDRCNHLRQNDKEEVPVFLLFLDCVWQL 203
PH-GRAM_MTMR12 cd13348
Myotubularian (MTM) related 12 protein (MTMR12) Pleckstrin Homology-Glucosyltransferases, ...
 26-202 2.29e-108

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: 325.66  E-value: 2.29e-108
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379  26 PEEIHTNEKEVTEKEVTLHLLPGEQLLCEASTVLKYVQEDSCQHGVYGRLVCTDFKIAFLGDDESALDNDeTQFKNKVIG 105
Cdd:cd13348    1 TEEEIKLEKEPQEKEVNPHLLPGEVVLCEANTVLKYTQDDGSQRGVYGRLVCTNFRIAFLGDDAPQDDNS-KQFKNKIYG 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 106 ENDITLHCVDQIYGVFDEKKKTLFGQL--KKYPEKLIIHCKDLRVFQFCLRYTKEEEVKRIVSGIIHHTQAPKLLKRLFL 183
Cdd:cd13348   80 ENDITLQCVDQIYGVYDEKKKLITGGLvkNKYPEKLIIHCKDLRVFQFCLRYTKEEEVKRIVSGIIHHTQEPKLLKRLFL 159

                        170
                 ....*....|....*....
gi 661567379 184 FSYATAAQNNTVTDPKNHT 202
Cdd:cd13348  160 FSYARAAPNNTVTKREAIM 178
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
 228-496 2.00e-53

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: 186.92  E-value: 2.00e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379  228 SVNEGYKVCERLPAYFVVPTPLPEENVQ---RFQGHG-IPIWCWsCH--NGSALLKmSALPK--------EQDDGILQ-I 292
Cdd:pfam06602  29 DINKDYKVCPTYPALLVVPKSISDETLKkaaKFRSKGrIPVLSY-RHkeNGAVITR-SSQPLvglngkrsIEDEKLLQaI 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379  293 QKSFLDGIYKTIH----RPP------------YEIvktEDLSSN----FLSLQEIQTAYSKFKQLFLIDNSTEfwDTDIK 352
Cdd:pfam06602 107 FKSSNPYSAKKLYivdaRPKlnamanrakgggYEN---EDNYPNckkiFLGIENIHVMRDSLNKLVEACNDRS--PSMDK 181

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379  353 WFSLLESSSWLDIIRRCLKKAIEITECMEAQNMNVLLLEENASDLCCLISSLVQLMMDPHCRTRIGFQSLIQKEWVMGGH 432
Cdd:pfam06602 182 WLSRLESSGWLKHIKAILDGACLIAQAVDLEGSSVLVHCSDGWDRTAQLTSLAQLLLDPYYRTIEGFQVLIEKEWLSFGH 261

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 661567379  433 CFLDRCNHLR--QNDKEEVPVFLLFLDCVWQLVHQHPPAFEFTETYLTVLSDSLYIPIFSTFFFNS 496
Cdd:pfam06602 262 KFADRCGHLAgfTDSKERSPVFLQFLDCVWQLLRQFPCAFEFNERFLIRLLYHLYSCQFGTFLCNS 327
3-PAP pfam12578
Myotubularin-associated protein; This domain family is found in eukaryotes, and is typically ...
 505-633 1.93e-49

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: 169.08  E-value: 1.93e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379  505 HQRQLSLPLTQSKSSP--KRGFFREETDHLIKNLLGKRISK---LINSSDELQdnFREFYDSWHSKSTDYHGLLLPHIEG 579
Cdd:pfam12578   1 KRRKKSYSSTLRGPPPslKNGLFRDEEDLLRRNSLLLRLKPdcpLHRSSDSND--SEQFFRDWFSKPADLHGLLLPLLSG 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 661567379  580 PEIKVWAQRYLRWIPEAQILGGGQVATLSKLLEMMEEVQSLQEKIDERHHSQQA 633
Cdd:pfam12578  79 PHIKLWKLCYLRWVPEAQINHGGPITAFHKLSLLADEVEALQRLLRQYRGGPSE 132
 
Name Accession Description Interval E-value
PTP-MTMR12 cd14594
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 260-462 1.14e-144

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: 420.02  E-value: 1.14e-144
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 260 HGIPIWCWSCHNGSALLKMSALPKEQDDGILQIQKSFLDGIYKTIHRPPYEIVKTEDLSSNFLSLQEIQTAYSKFKQLFL 339
Cdd:cd14594    1 RGIPIWCWSCHNGCALLKMSALPKEQDDVALQDQKSFLDRIYKTLSRPPYESVKTEDLSASLPSLQEIQTAYNRFKQLFL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 340 IDNSTEFWDTDIKWFSLLESSSWLDIIRRCLKKAIEITECMEAQNMNVLLLEENASDLCCLISSLVQLMMDPHCRTRIGF 419
Cdd:cd14594   81 IDNSTDFWDTDVKWFSSLESSNWLEIIRQCLKKAVEVVECLEKQNTNVLLTEEEATDLCCVISSLVQIMMDPYCRTKSGF 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|...
gi 661567379 420 QSLIQKEWVMGGHCFLDRCNHLRQNDKEEVPVFLLFLDCVWQL 462
Cdd:cd14594  161 QSLIQKEWVMGGHCFLDRCNHLRQNDKEEVPVFLLFLDCVWQL 203
PH-GRAM_MTMR12 cd13348
Myotubularian (MTM) related 12 protein (MTMR12) Pleckstrin Homology-Glucosyltransferases, ...
 26-202 2.29e-108

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: 325.66  E-value: 2.29e-108
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379  26 PEEIHTNEKEVTEKEVTLHLLPGEQLLCEASTVLKYVQEDSCQHGVYGRLVCTDFKIAFLGDDESALDNDeTQFKNKVIG 105
Cdd:cd13348    1 TEEEIKLEKEPQEKEVNPHLLPGEVVLCEANTVLKYTQDDGSQRGVYGRLVCTNFRIAFLGDDAPQDDNS-KQFKNKIYG 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 106 ENDITLHCVDQIYGVFDEKKKTLFGQL--KKYPEKLIIHCKDLRVFQFCLRYTKEEEVKRIVSGIIHHTQAPKLLKRLFL 183
Cdd:cd13348   80 ENDITLQCVDQIYGVYDEKKKLITGGLvkNKYPEKLIIHCKDLRVFQFCLRYTKEEEVKRIVSGIIHHTQEPKLLKRLFL 159

                        170
                 ....*....|....*....
gi 661567379 184 FSYATAAQNNTVTDPKNHT 202
Cdd:cd13348  160 FSYARAAPNNTVTKREAIM 178
PTP-MTMR10-like cd14537
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 260-461 5.64e-99

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: 302.34  E-value: 5.64e-99
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 260 HGIPIWCWSCHNGSALLKMSALPKeqddgilQIQKSFLDGIYKTIHRPPY---EIVKTEDLSSNFLSLQEIQTAYSKFKQ 336
Cdd:cd14537    1 GRPPVWCWSHPNGAALVRMAELLP-------TITDRTQENKMLEAIRKSHpnlKKPKVIDLDKLLPSLQDVQAAYLKLRE 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 337 LFLIDNSTEFWDTDIKWFSLLESSSWLDIIRRCLKKAIEITECMEAQNMNVLLLEENASDLCCLISSLVQLMMDPHCRTR 416
Cdd:cd14537   74 LCTPDSSEQFWVQDSKWYSLLENTKWLHYVSACLKKASEAAEALESRGRSVVLQESDGRDLSCVVSSLVQLLLDPHFRTI 153

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*..
gi 661567379 417 IGFQSLIQKEWVMGGHCFLDRCNHLR--QNDKEEVPVFLLFLDCVWQ 461
Cdd:cd14537  154 TGFQSLIQKEWVALGHPFCDRLGHVKpnKTESEESPVFLLFLDCVWQ 200
PTP-MTMR10 cd14593
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 262-461 1.04e-64

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: 212.44  E-value: 1.04e-64
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 262 IPIWCWSCHNGSALLKMSALpkeqDDGILQ--IQKSFLDGIYKTihRPPYEIVKTEDLSSNFLSLQEIQTAYSKFKQLFL 339
Cdd:cd14593    3 IPLWCWNHPNGSALVRMANI----KDLLQQrkIDQRICNAITRS--HPLRSDVYKSDLDKTLPNIQEIQAAFVKLKQLCV 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 340 IDnstEFWDTDIKWFSLLESSSWLDIIRRCLKKAIEITECMEAQNMNVLLLEENASDLCCLISSLVQLMMDPHCRTRIGF 419
Cdd:cd14593   77 NE---PFEETEEKWLSSLESTRWLEYVRAFLKHSAELVYMLESKHVSVILQEEEGRDLSCVVASLVQVMLDPYFRTITGF 153

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|..
gi 661567379 420 QSLIQKEWVMGGHCFLDRCNHLRQNDKEEVPVFLLFLDCVWQ 461
Cdd:cd14593  154 QSLIQKEWVMAGYRFLDRCNHLKKSSKKESPLFLLFLDCVWQ 195
PH-GRAM_MTMR10-like cd13212
Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins ...
 46-169 1.72e-63

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: 206.70  E-value: 1.72e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379  46 LPGEQLLCEASTVLKYVQEDSCQHGVYGRLVCTDFKIAFLGDDESALDNdeTQFKNKVIGENDITLHCVDQIYGVFDEK- 124
Cdd:cd13212    1 LPGEQVLAEAPGVRKGLQEDSSQPELSGTLICTNFKITFQPDDWQWLDN--TQQKNPLNGEYDFALVCIGQIEAVSDLKr 78

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
gi 661567379 125 --KKTLFGQLKKYPEKLIIHCKDLRVFQFCLRYTKEEEVKRIVSGII 169
Cdd:cd13212   79 vqLLRPGSLLKFIPEELIIHCKDFRVLRFGFEATGGEEPKAFQVTIA 125
PTP-MTMR11 cd14595
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 262-462 1.47e-56

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: 190.81  E-value: 1.47e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 262 IPIWCWSCHNGSALLKMSALPKEQD---DGILQIQKSFLDGIYKTIhrppyeIVkteDLSSNFLSLQEIQTAYSKFKQLF 338
Cdd:cd14595    3 IPRWCWHHPGGSDLLRMAGFYTNSDpekEDIRSVELLLQAGHSQCV------IV---DTSEELPSPADIQLAYLKLRTLC 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 339 LIDNSTefWDTDIKWFSLLESSSWLDIIRRCLKKAIEITECMEAQNMNVLLLEENASDLCCLISSLVQLMMDPHCRTRIG 418
Cdd:cd14595   74 LPDISV--SVSDEKWLSNLEGTRWLDHVRACLRKASEVSCLLAERHRSVILQESEDRDLNCLLSSLVQLLSDPHARTISG 151

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....
gi 661567379 419 FQSLIQKEWVMGGHCFLDRCNHLRQNDKEEVPVFLLFLDCVWQL 462
Cdd:cd14595  152 FQSLVQKEWVVAGHPFLQRLNLTRESDKEESPVFLLFLDCVWQL 195
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
 228-496 2.00e-53

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: 186.92  E-value: 2.00e-53
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379  228 SVNEGYKVCERLPAYFVVPTPLPEENVQ---RFQGHG-IPIWCWsCH--NGSALLKmSALPK--------EQDDGILQ-I 292
Cdd:pfam06602  29 DINKDYKVCPTYPALLVVPKSISDETLKkaaKFRSKGrIPVLSY-RHkeNGAVITR-SSQPLvglngkrsIEDEKLLQaI 106

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379  293 QKSFLDGIYKTIH----RPP------------YEIvktEDLSSN----FLSLQEIQTAYSKFKQLFLIDNSTEfwDTDIK 352
Cdd:pfam06602 107 FKSSNPYSAKKLYivdaRPKlnamanrakgggYEN---EDNYPNckkiFLGIENIHVMRDSLNKLVEACNDRS--PSMDK 181

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379  353 WFSLLESSSWLDIIRRCLKKAIEITECMEAQNMNVLLLEENASDLCCLISSLVQLMMDPHCRTRIGFQSLIQKEWVMGGH 432
Cdd:pfam06602 182 WLSRLESSGWLKHIKAILDGACLIAQAVDLEGSSVLVHCSDGWDRTAQLTSLAQLLLDPYYRTIEGFQVLIEKEWLSFGH 261

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 661567379  433 CFLDRCNHLR--QNDKEEVPVFLLFLDCVWQLVHQHPPAFEFTETYLTVLSDSLYIPIFSTFFFNS 496
Cdd:pfam06602 262 KFADRCGHLAgfTDSKERSPVFLQFLDCVWQLLRQFPCAFEFNERFLIRLLYHLYSCQFGTFLCNS 327
3-PAP pfam12578
Myotubularin-associated protein; This domain family is found in eukaryotes, and is typically ...
 505-633 1.93e-49

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: 169.08  E-value: 1.93e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379  505 HQRQLSLPLTQSKSSP--KRGFFREETDHLIKNLLGKRISK---LINSSDELQdnFREFYDSWHSKSTDYHGLLLPHIEG 579
Cdd:pfam12578   1 KRRKKSYSSTLRGPPPslKNGLFRDEEDLLRRNSLLLRLKPdcpLHRSSDSND--SEQFFRDWFSKPADLHGLLLPLLSG 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 661567379  580 PEIKVWAQRYLRWIPEAQILGGGQVATLSKLLEMMEEVQSLQEKIDERHHSQQA 633
Cdd:pfam12578  79 PHIKLWKLCYLRWVPEAQINHGGPITAFHKLSLLADEVEALQRLLRQYRGGPSE 132
PTP-MTM-like cd14507
protein tyrosine phosphatase-like domain of myotubularins; Myotubularins are a unique subgroup ...
 262-461 1.45e-41

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: 150.78  E-value: 1.45e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 262 IPIWCWSC-HNGSALLKmSALPKeqdDGILQiQKSFLDGIY-----------KTIH----RPPY----EIVK---TEDLS 318
Cdd:cd14507    3 IPVLSWRHpRNGAVICR-SSQPL---VGLTG-SRSKEDEKLlnairkaspssKKLYivdaRPKLnavaNRAKgggYENTE 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 319 S------NFLSLQEIQTAYSKFKQLFLIDNSTEfwDTDIKWFSLLESSSWLDIIRRCLKKAIEITECMEAQNMNVLLLEE 392
Cdd:cd14507   78 YypncelEFLNIENIHAMRDSLNKLRDACLSPN--DEESNWLSALESSGWLEHIRLILKGAVRVADLLEKEGTSVLVHCS 155

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 661567379 393 NASDLCCLISSLVQLMMDPHCRTRIGFQSLIQKEWVMGGHCFLDRCNHLR--QNDKEEVPVFLLFLDCVWQ 461
Cdd:cd14507  156 DGWDRTSQLTSLAQLLLDPYYRTIEGFQVLIEKEWLSFGHKFADRCGHGDknSSDEERSPIFLQFLDCVWQ 226
PTP-MTMR6-like cd14532
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases ...
 221-485 4.93e-35

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: 134.78  E-value: 4.93e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 221 NMKYKAVSVNEGYKVCERLPAYFVVPTPLPEENVQ---RFQGHG-IPIW--------CWSCHNGSALLKMSALPKEqDDG 288
Cdd:cd14532   12 NDNWTLSDINKDYELCDTYPRELFVPTSASTPVLVgssKFRSKGrLPVLsylhkdnqAAICRCSQPLSGFSARCVE-DEQ 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 289 ILQ-IQKS--FLDGIYKTIHRPP------------YEivkTEDLSSN----FLSLQEIQTAY-SKFKQLFLIDNST---- 344
Cdd:cd14532   91 LLQaIRKAnpNSKFMYVVDTRPKinamankaagkgYE---NEDNYSNikfqFFGIENIHVMRsSLQKLLEVCELKNpsms 167

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 345 EFWDTdikwfslLESSSWLDIIRRCLKKAIEITECMEaQNMNVLLLEENASDLCCLISSLVQLMMDPHCRTRIGFQSLIQ 424
Cdd:cd14532  168 AFLSG-------LESSGWLKHIKAVMDTSVFIAKAVS-EGASVLVHCSDGWDRTAQTCSLASLLLDPYYRTIKGFQVLIE 239

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 661567379 425 KEWVMGGHCFLDRCNHLRQNDKEEVPVFLLFLDCVWQLVHQHPPAFEFTETYLTVLSDSLY 485
Cdd:cd14532  240 KEWLSFGHKFTDRCGHLQGDAKEVSPVFTQFLDCVWQLMQQFPRAFEFNERFLLTLHDHVY 300
PTP-MTM1-like cd14535
protein tyrosine phosphatase-like domain of myotubularin, and myotubularin related ...
 350-485 1.33e-31

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: 123.71  E-value: 1.33e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 350 DIKWFSLLESSSWLDIIRRCLKKAIEITECMEAQNMNVLLLEENASDLCCLISSLVQLMMDPHCRTRIGFQSLIQKEWVM 429
Cdd:cd14535  112 DSHWLSNLESTHWLEHIKLILAGAVRIADKVESGKTSVVVHCSDGWDRTAQLTSLAMLMLDPYYRTIRGFEVLIEKEWLS 191

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 661567379 430 GGHCFLDRCNHLRQN--DKEEVPVFLLFLDCVWQLVHQHPPAFEFTETYLTVLSDSLY 485
Cdd:cd14535  192 FGHKFAQRIGHGDKNhsDADRSPVFLQFIDCVWQMTRQFPNAFEFNEHFLITILDHLY 249
PTP-MTMR9 cd14536
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 352-461 5.02e-31

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: 120.91  E-value: 5.02e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 352 KWFSLLESSSWLDIIRRCLKKAIEITECMEAQNMNVLLLEENASDLCCLISSLVQLMMDPHCRTRIGFQSLIQKEWVMGG 431
Cdd:cd14536  112 KWLSKLESSNWLSHVKEILTTACLVAQCIDREGASVLVHGSEGMDSTLQVTSLAQIILDPDCRTIRGFEALIEREWLQAG 191

                         90       100       110
                 ....*....|....*....|....*....|...
gi 661567379 432 HCFLDRCNHL---RQNDKEEVPVFLLFLDCVWQ 461
Cdd:cd14536  192 HPFQSRCAKSaysNSKQKFESPVFLLFLDCVWQ 224
PTP-MTM1 cd14591
protein tyrosine phosphatase-like domain of myotubularin phosphoinositide phosphatase 1; ...
 353-485 9.57e-31

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: 121.29  E-value: 9.57e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 353 WFSLLESSSWLDIIRRCLKKAIEITECMEAQNMNVLLLEENASDLCCLISSLVQLMMDPHCRTRIGFQSLIQKEWVMGGH 432
Cdd:cd14591  115 WLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSYYRTIEGFEVLVQKEWISFGH 194

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 661567379 433 CFLDRCNHLRQN--DKEEVPVFLLFLDCVWQLVHQHPPAFEFTETYLTVLSDSLY 485
Cdd:cd14591  195 KFASRIGHGDKNhaDADRSPIFLQFIDCVWQMSKQFPTAFEFNEQFLITILDHLY 249
PTP-MTMR6 cd14585
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 221-485 1.21e-29

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: 119.26  E-value: 1.21e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 221 NMKYKAVSVNEGYKVCERLPAYFVVPTPLPEENV---QRFQGHG-IPIWCWS--------CHNGSALLKMSALPKEqDDG 288
Cdd:cd14585   12 NDYWQLSDVNRDYKICDTYPRDLYVPITASKPIIvgsSKFRSKGrFPVLSYYhqekkaaiCRCSQPLSGFSARCLE-DEH 90

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 289 ILQ-IQKSFLDG--IYKTIHRPPYEIV---------KTEDLSSN----FLSLQEIQTAYSKFKQLFLIDNSTEFWDTDik 352
Cdd:cd14585   91 MLQaISKANPNNryMYVMDTRPKLNAManraagkgyENEDNYSNirfqFVGIENIHVMRSSLQKLLEVCGTKALSVND-- 168

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 353 WFSLLESSSWLDIIRRCLKKAIEITECMEAQNMNVLLLEENASDLCCLISSLVQLMMDPHCRTRIGFQSLIQKEWVMGGH 432
Cdd:cd14585  169 FLSGLESSGWLRHIKAVLDAAVFLAKAVAVEGASVLVHCSDGWDRTAQVCSLGSLLLDPYYRTIKGFMVLIEKDWISFGH 248

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|...
gi 661567379 433 CFLDRCNHLRQNDKEEVPVFLLFLDCVWQLVHQHPPAFEFTETYLTVLSDSLY 485
Cdd:cd14585  249 KFSDRCGQLDGDPKEISPVFTQFLECVWQLTEQFPRAFEFSEAFLLQIHEHIH 301
PTP-MTMR2 cd14590
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 353-485 1.79e-29

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: 117.83  E-value: 1.79e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 353 WFSLLESSSWLDIIRRCLKKAIEITECMEAQNMNVLLLEENASDLCCLISSLVQLMMDPHCRTRIGFQSLIQKEWVMGGH 432
Cdd:cd14590  128 WLSNLESTHWLEHIKLILAGALRIADKVESGKTSVVVHCSDGWDRTAQLTSLAMLMLDGYYRTIRGFEVLVEKEWLSFGH 207

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 661567379 433 CFLDRCNHLRQN--DKEEVPVFLLFLDCVWQLVHQHPPAFEFTETYLTVLSDSLY 485
Cdd:cd14590  208 RFQLRVGHGDKNhaDADRSPVFLQFIDCVWQMTRQFPTAFEFNEYFLITILDHLY 262
PTP-MTMR1 cd14592
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 352-485 3.97e-29

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: 116.62  E-value: 3.97e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 352 KWFSLLESSSWLDIIRRCLKKAIEITECMEAQNMNVLLLEENASDLCCLISSLVQLMMDPHCRTRIGFQSLIQKEWVMGG 431
Cdd:cd14592  114 RWLSNVDGTHWLEYIRMLLAGAVRIADKIESGKTSVVVHCSDGWDRTAQLTSLAMLMLDSYYRTIKGFEVLIEKEWISFG 193

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 661567379 432 HCFLDRCNHLRQN--DKEEVPVFLLFLDCVWQLVHQHPPAFEFTETYLTVLSDSLY 485
Cdd:cd14592  194 HRFALRVGHGDDNhaDADRSPIFLQFIDCVWQMTRQFPSAFEFNELFLITILDHLY 249
PTP-MTMR7 cd14583
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 221-485 2.24e-28

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: 115.83  E-value: 2.24e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 221 NMKYKAVSVNEGYKVCERLPAYFVVPTPLPEENV---QRFQGHG-IPIWCWSCHNGSALLKMSALPKE-------QDDGI 289
Cdd:cd14583   12 NSLWQVSDVNRDYRVCDTYPTELYVPKSATAPIIvgsSKFRSRGrFPVLSYYCKDNNASICRSSQPLSgfsarclEDEQM 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 290 LQ-IQKSF--LDGIYKTIHRPPYEIV---------KTEDLSSN----FLSLQEIQTAYSKFKQLFLIDNSTEFWDTDIKW 353
Cdd:cd14583   92 LQaIRKANpgSDFMYVVDTRPKLNAManraagkgyENEDNYSNikfqFIGIENIHVMRNSLQKMLEVCELRSPSMGDFLW 171

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 354 FslLESSSWLDIIRRCLKKAIEITECMEAQNMNVLLLEENASDLCCLISSLVQLMMDPHCRTRIGFQSLIQKEWVMGGHC 433
Cdd:cd14583  172 G--LENSGWLKHIKAIMDAGIFIAKAVAEEGASVLVHCSDGWDRTAQVCSVASLLLDPYYRTIKGFMVLIEKDWVSFGHK 249

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 661567379 434 FLDRCNHLRQNDKEEVPVFLLFLDCVWQLVHQHPPAFEFTETYLTVLSDSLY 485
Cdd:cd14583  250 FNHRYGHLDGDPKEVSPVIDQFIECVWQLMEQFPCAFEFNERFLIHIHHHIY 301
PTP-MTMR8 cd14584
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 221-485 2.45e-28

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: 115.74  E-value: 2.45e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 221 NMKYKAVSVNEGYKVCERLPAYFVVPTPLPEENV---QRFQGHG-IPIWCWSCHNGSALLKMSALPK-------EQDDGI 289
Cdd:cd14584   18 NDYWEITDANKNYEICSTYPPELVVPKSASKATVvgsSKFRSRGrFPVLSYLYKENNAAICRCSQPLsgfsarcVEDEQM 97

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 290 LQIQKSFLDG---IYKTIHRPPYEIV---------KTEDLSSN----FLSLQEIQTAYSKFKQLFLIDNSTEFWDTDikW 353
Cdd:cd14584   98 LQAISKANPGspfMYVVDTRPKLNAManraagkgyENEDNYSNirfqFIGIENIHVMRSSLQKLLEVCEMKSPSMSD--F 175

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 354 FSLLESSSWLDIIRRCLKKAIEITECMEAQNMNVLLLEENASDLCCLISSLVQLMMDPHCRTRIGFQSLIQKEWVMGGHC 433
Cdd:cd14584  176 LTGLENSGWLRHIKAVMDAGVFLAKAVKEEKASVLVHCSDGWDRTAQVCSLASLLLDPFYRTIKGLMVLIEKEWISMGHK 255

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|..
gi 661567379 434 FLDRCNHLRQNDKEEVPVFLLFLDCVWQLVHQHPPAFEFTETYLTVLSDSLY 485
Cdd:cd14584  256 FSQRCGHLDGDPKEVSPVFTQFLECVWQLMEQFPCAFEFNEHFLLEIHDHVF 307
PTP-MTMR5-like cd14534
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 228-465 9.23e-28

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: 113.23  E-value: 9.23e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 228 SVNEGYKVCERLPAYFVVPTPLPEENVQR----FQGHGIPIWCWSCHNGSALL-------------------KMSALPK- 283
Cdd:cd14534    5 TANRDYSICRSYPALVVVPQSVSDESLRKvarcYRQGRFPVVTWRHPRTKALLlrsggfhgkgvmgmlksanTSTSSPTv 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 284 ---------EQDDGILQI------QKSFLdgiyKTIHRPPYEivKTEDLSSNFLSLQEIQTAYSKFKQ-----LFLIDNS 343
Cdd:cd14534   85 sssetssslEQEKYLSALvlyvlgEKSQM----KGVKAESDP--KCEFIPVEYPEVRQVKASFKKLLRacvpsSAPTEPE 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 344 TEFwdtdikwFSLLESSSWLDIIRRCLKKAIEITECMEAQNMNVLLLEENASDLCCLISSLVQLMMDPHCRTRIGFQSLI 423
Cdd:cd14534  159 QSF-------LKAVEDSEWLQQLQCLMQLSGAVVDLLDVQGSSVLLCLEDGWDVTTQVSSLSQLLLDPYYRTLEGFRVLV 231

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|...
gi 661567379 424 QKEWVMGGHCFLDRCNHLRQNDKEE-VPVFLLFLDCVWQLVHQ 465
Cdd:cd14534  232 EKEWLAFGHRFSHRSNLTAASQSSGfAPVFLQFLDAVHQIHRQ 274
PH-GRAM_MTMR10 cd13346
Myotubularian (MTM) related 10 protein (MTMR10) Pleckstrin Homology-Glucosyltransferases, ...
 39-195 2.41e-27

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: 108.86  E-value: 2.41e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379  39 KEVTLHLLPGEQLLCEASTVLKYVQEDSCQHGVYGRLVCTDFKIAFLGDDesALDNDETQFKNKVIGENDITLHCVDQIY 118
Cdd:cd13346   12 KKLEPVLLPGEIVVNEVNFVRKCIATDTSQYDLWGKLICTNFKISFITDD--PMPLQKFHYKNLLLGEHDVPLTCIEQIV 89

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 119 GVFDEKKK-TLFG---QLKKYPEKLIIHCKDLRVFQFCLRYTKEEEVKRIVSGIIHHTQaPKLLKRLFLFSYATAAQNNT 194
Cdd:cd13346   90 TVNDTKRKqKVLGpnqKLKFNPTELIIYCKDFRIVRFRFDEAGPESAKKVCLAIAHYSQ-PTDLQLLFAFEYVGKKYHNS 168


                 .
gi 661567379 195 V 195
Cdd:cd13346  169 A 169
PTP-MTMR3-like cd14533
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases ...
 353-461 9.86e-23

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: 97.47  E-value: 9.86e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 353 WFSLLESSSWLDIIRRCLKKAIEITECMEAQNMNVLLLEENASDLCCLISSLVQLMMDPHCRTRIGFQSLIQKEWVMGGH 432
Cdd:cd14533  119 WLSNLESTKWLHHLSGLLKAALLVVNAVDEEGRPVLVHCSDGWDRTPQIVALAELMLDPYYRTIEGFQVLVEREWLDFGH 198

                         90       100       110
                 ....*....|....*....|....*....|.
gi 661567379 433 CFLDRCNHLRQND--KEEVPVFLLFLDCVWQ 461
Cdd:cd14533  199 KFADRCGHGVNSEdiNERCPVFLQWLDCVHQ 229
PTP-MTMR13 cd14589
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 224-465 9.28e-20

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: 90.37  E-value: 9.28e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 224 YKAVSVNEGYKVCERLPAYFVVPTPLPEENVQR----FQGHGIPIWCW-SCHNGSALLKM------------------SA 280
Cdd:cd14589    1 FRITAVNRMYSLCRSYPGLLVVPQSVQDSSLQKvarcYRHNRLPVVCWkNSKTKAVLLRSggfhgkgvvglfksqnphSA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 281 LPKEQDDGILQIQKSFLDGIYKTI-------------------HRPPYEIVKTEDLSSNF------------LSLQEIQT 329
Cdd:cd14589   81 APASSESSSSIEQEKYLQALLNAIsvhqkmngnstllqsqllkRQAALYIFGEKSQLRGFkldfalncefvpVEFHDIRQ 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 330 AYSKFKQLF-LIDNSTEFWDTDIKWFSLLESSSWLDIIRRCLKKAIEITECMEAQNmNVLLLEENASDLCCLISSLVQLM 408
Cdd:cd14589  161 VKASFKKLMrACVPSTIPTDSEVTFLKALGESEWFLQLHRIMQLAVVISELLESGS-SVMVCLEDGWDITTQVVSLVQLL 239

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 661567379 409 MDPHCRTRIGFQSLIQKEWVMGGHCFLDRCNhLRQNDKEE--VPVFLLFLDCVWQLVHQ 465
Cdd:cd14589  240 SDPFYRTLEGFQMLVEKEWLSFGHKFSQRSN-LTPNSQGSgfAPIFLQFLDCVHQIHNQ 297
PTP-MTM-like_fungal cd17666
protein tyrosine phosphatase-like domain of fungal myotubularins; Myotubularins are a unique ...
 356-461 1.27e-19

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: 88.27  E-value: 1.27e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 356 LLESSSWLDIIRRCLKKAIEITECMEAQNMNVLLLEENASDLCCLISSLVQLMMDPHCRTRIGFQSLIQKEWVMGGHCFL 435
Cdd:cd17666  129 ALKKSNWLKYLAIILQGADLIAKSIHFNHSHVLIHCSDGWDRTSQLSALAQLCLDPYYRTLEGFMVLVEKDWLSFGHRFA 208

                         90       100
                 ....*....|....*....|....*.
gi 661567379 436 DRCNHlrqndKEEVPVFLLFLDCVWQ 461
Cdd:cd17666  209 ERSGH-----KETSPVFHQFLDCVYQ 229
PTP-MTMR5 cd14588
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 224-462 1.61e-19

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: 89.64  E-value: 1.61e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 224 YKAVSVNEGYKVCERLPAYFVVPTPLPEENVQR----FQGHGIPIWCW-SCHNGSALLKMSAL----------------- 281
Cdd:cd14588    1 FRISTVNRMYAVCRSYPGLLIVPQSIQDNTIQRisrcYRQNRFPVVCWrNSRTKAVLLRSGGLhgkgvvglfksqnapaa 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 282 -PKEQDDGILQiQKSFLDGIYKTIhrPPYEIVKTEDLSSNF----------------------------LSLQEIQTAYS 332
Cdd:cd14588   81 gQSQTDSTSLE-QEKYLQAVINSM--PRYADASGRNTLSGFraalyiigdksqlkgvkqdplqqwevvpIEVFDVRQVKA 157

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 333 KFKQLF--LIDNSTEFwDTDIKWFSLLESSSWLDIIRRCLKKAIEITECMEAQNmNVLLLEENASDLCCLISSLVQLMMD 410
Cdd:cd14588  158 SFKKLMkaCVPSCPST-DPSQTYLRTLEESEWLSQLHKLLQVSVLVVELLDSGS-SVLVSLEDGWDITTQVVSLVQLLSD 235

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|...
gi 661567379 411 PHCRTRIGFQSLIQKEWVMGGHCFLDRCNH-LRQNDKEEVPVFLLFLDCVWQL 462
Cdd:cd14588  236 PYYRTIEGFRLLVEKEWLSFGHRFSHRGAQtLASQSSGFTPVFLQFLDCVHQI 288
PTP-MTMR3 cd14586
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 321-461 9.35e-19

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: 87.77  E-value: 9.35e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 321 FLSLQEIQTAYSKFKQLFLIdnSTEFWDTDiKWFSLLESSSWLDIIRRCLKKAIEITECMEAQNMNVLLLEENASDLCCL 400
Cdd:cd14586  178 FMGMANIHSIRKSFQSLRLL--CTQMPDPA-NWLSALESTKWLQHLSMLLKSALLVVHAVDRDQRPVLVHCSDGWDRTPQ 254

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 661567379 401 ISSLVQLMMDPHCRTRIGFQSLIQKEWVMGGHCFLDRCNHLRQND--KEEVPVFLLFLDCVWQ 461
Cdd:cd14586  255 IVALSKLLLDPYYRTIEGFQVLVETEWLDFGHKFADRCGHGENSDdlNERCPVFLQWLDCVHQ 317
PTP-MTMR4 cd14587
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 353-461 3.11e-18

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: 86.24  E-value: 3.11e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379 353 WFSLLESSSWLDIIRRCLKKAIEITECMEAQNMNVLLLEENASDLCCLISSLVQLMMDPHCRTRIGFQSLIQKEWVMGGH 432
Cdd:cd14587  198 WLSALESTKWLQHLSVMLKAAVLVASAVDREGRPVLVHCSDGWDRTPQIVALAKILLDPYYRTIEGFQVLVETDWLDFGH 277

                         90       100       110
                 ....*....|....*....|....*....|.
gi 661567379 433 CFLDRCNHL--RQNDKEEVPVFLLFLDCVWQ 461
Cdd:cd14587  278 KFGDRCGHQenVEDQNEQCPVFLQWLDCVHQ 308
PH-GRAM_MTMR11 cd15790
Myotubularian (MTM) related 11 protein (MTMR11) Pleckstrin Homology-Glucosyltransferases, ...
 46-154 1.25e-15

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: 73.66  E-value: 1.25e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 661567379  46 LPGEQLLCEASTVLKYVQEDSCQHGVYGRLVCTDFKIAFLGDD-ESALDNDETQFKNkvigENDITLHCVDQIYGVFDEK 124
Cdd:cd15790    1 LPGEHILEEAVRVRKLVQWRDGEGFLSGTLYCTNFRVAFVPEHiQKDENDHDTVLNS----EHDIALPSIDRVVAVQGPT 76

                         90       100       110
                 ....*....|....*....|....*....|...
gi 661567379 125 KKTLF---GQLKKYPEKLIIHCKDLRVFQFCLR 154
Cdd:cd15790   77 TMKAVtasSGLKFIPEELVIYCRDFRLLRFQFE 109
 
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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