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Conserved domains on  [gi|767984582|ref|XP_011520040|]
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myotubularin-related protein 10 isoform X4 [Homo sapiens]

Protein Classification

PH-GRAM_MTMR10 and PTP-MTMR10 domain-containing protein( domain architecture ID 12988801)

PH-GRAM_MTMR10 and PTP-MTMR10 domain-containing protein

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PTP-MTMR10 cd14593
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 279-472 8.37e-143

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: 409.28  E-value: 8.37e-143
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 279 RRMPLWCWSHSNGSALVRMALIKDVLQQRKIDQRICNAITKSHPQRSDVYKSDLDKTLPNIQEVQAAFVKLKQLCVNEPF 358
Cdd:cd14593    1 RRIPLWCWNHPNGSALVRMANIKDLLQQRKIDQRICNAITRSHPLRSDVYKSDLDKTLPNIQEIQAAFVKLKQLCVNEPF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 359 EETEEKWLSSLENTRWLEYVRAFLKHSAELVYMLESKHLSVVLQEEEGRDLSCCVASLVQVMLDPYFRTITGFQSLIQKE 438
Cdd:cd14593   81 EETEEKWLSSLESTRWLEYVRAFLKHSAELVYMLESKHVSVILQEEEGRDLSCVVASLVQVMLDPYFRTITGFQSLIQKE 160

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 767984582 439 WVMAGYQFLDRCNHLKRS-EKESPLFLLFLDATWQ 472
Cdd:cd14593  161 WVMAGYRFLDRCNHLKKSsKKESPLFLLFLDCVWQ 195
PH-GRAM_MTMR10 cd13346
Myotubularian (MTM) related 10 protein (MTMR10) Pleckstrin Homology-Glucosyltransferases, ...
 21-195 8.32e-136

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: 390.83  E-value: 8.32e-136
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582  21 TDDKINSEPKIKKLEPVLLPGEIVVNEVNFVRKCIATDTSQYDLWGKLICSNFKISFITDDPMPLQKFHYRNLLLGEHDV 100
Cdd:cd13346    1 TDDKINSEPKIKKLEPVLLPGEIVVNEVNFVRKCIATDTSQYDLWGKLICTNFKISFITDDPMPLQKFHYKNLLLGEHDV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 101 PLTCIEQIVTVNDHKRKQKVLGPNQKLKFNPTELIIYCKDFRIVRFRFDESGPESAKKVCLAIAHYSQPTDLQLLFAFEY 180
Cdd:cd13346   81 PLTCIEQIVTVNDTKRKQKVLGPNQKLKFNPTELIIYCKDFRIVRFRFDEAGPESAKKVCLAIAHYSQPTDLQLLFAFEY 160

                        170
                 ....*....|....*
gi 767984582 181 VGKKYHNSANKINGI 195
Cdd:cd13346  161 VGKKYHNSAGKVNGI 175
 
Name Accession Description Interval E-value
PTP-MTMR10 cd14593
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 279-472 8.37e-143

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: 409.28  E-value: 8.37e-143
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 279 RRMPLWCWSHSNGSALVRMALIKDVLQQRKIDQRICNAITKSHPQRSDVYKSDLDKTLPNIQEVQAAFVKLKQLCVNEPF 358
Cdd:cd14593    1 RRIPLWCWNHPNGSALVRMANIKDLLQQRKIDQRICNAITRSHPLRSDVYKSDLDKTLPNIQEIQAAFVKLKQLCVNEPF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 359 EETEEKWLSSLENTRWLEYVRAFLKHSAELVYMLESKHLSVVLQEEEGRDLSCCVASLVQVMLDPYFRTITGFQSLIQKE 438
Cdd:cd14593   81 EETEEKWLSSLESTRWLEYVRAFLKHSAELVYMLESKHVSVILQEEEGRDLSCVVASLVQVMLDPYFRTITGFQSLIQKE 160

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 767984582 439 WVMAGYQFLDRCNHLKRS-EKESPLFLLFLDATWQ 472
Cdd:cd14593  161 WVMAGYRFLDRCNHLKKSsKKESPLFLLFLDCVWQ 195
PH-GRAM_MTMR10 cd13346
Myotubularian (MTM) related 10 protein (MTMR10) Pleckstrin Homology-Glucosyltransferases, ...
 21-195 8.32e-136

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: 390.83  E-value: 8.32e-136
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582  21 TDDKINSEPKIKKLEPVLLPGEIVVNEVNFVRKCIATDTSQYDLWGKLICSNFKISFITDDPMPLQKFHYRNLLLGEHDV 100
Cdd:cd13346    1 TDDKINSEPKIKKLEPVLLPGEIVVNEVNFVRKCIATDTSQYDLWGKLICTNFKISFITDDPMPLQKFHYKNLLLGEHDV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 101 PLTCIEQIVTVNDHKRKQKVLGPNQKLKFNPTELIIYCKDFRIVRFRFDESGPESAKKVCLAIAHYSQPTDLQLLFAFEY 180
Cdd:cd13346   81 PLTCIEQIVTVNDTKRKQKVLGPNQKLKFNPTELIIYCKDFRIVRFRFDEAGPESAKKVCLAIAHYSQPTDLQLLFAFEY 160

                        170
                 ....*....|....*
gi 767984582 181 VGKKYHNSANKINGI 195
Cdd:cd13346  161 VGKKYHNSAGKVNGI 175
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
 226-512 1.01e-69

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: 226.59  E-value: 1.01e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582  226 DWDREIKRTGA---SGWRVCSINEGYMISTCLPEYIVVPSSLADQDLKIFSHSFVGRRMPLWCWSH-SNGSALVRMA--L 299
Cdd:pfam06602   9 DPEAEFARQGLpskDEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHkENGAVITRSSqpL 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582  300 IkDVLQQRKI-DQRICNAITKSHPQRS----------------------------DVYKSD----LDktLPNIQEVQAAF 346
Cdd:pfam06602  89 V-GLNGKRSIeDEKLLQAIFKSSNPYSakklyivdarpklnamanrakgggyeneDNYPNCkkifLG--IENIHVMRDSL 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582  347 VKLKQLCvnEPFEETEEKWLSSLENTRWLEYVRAFLKHSAELVYMLESKHLSVVLQEEEGRDLSCCVASLVQVMLDPYFR 426
Cdd:pfam06602 166 NKLVEAC--NDRSPSMDKWLSRLESSGWLKHIKAILDGACLIAQAVDLEGSSVLVHCSDGWDRTAQLTSLAQLLLDPYYR 243

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582  427 TITGFQSLIQKEWVMAGYQFLDRCNHL---KRSEKESPLFLLFLDATWQLLEQYPAAFEFSETYLAVLYDSTRISLFGTF 503
Cdd:pfam06602 244 TIEGFQVLIEKEWLSFGHKFADRCGHLagfTDSKERSPVFLQFLDCVWQLLRQFPCAFEFNERFLIRLLYHLYSCQFGTF 323


                  ....*....
gi 767984582  504 LFNSPHQRV 512
Cdd:pfam06602 324 LCNSEKERV 332
 
Name Accession Description Interval E-value
PTP-MTMR10 cd14593
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 279-472 8.37e-143

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: 409.28  E-value: 8.37e-143
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 279 RRMPLWCWSHSNGSALVRMALIKDVLQQRKIDQRICNAITKSHPQRSDVYKSDLDKTLPNIQEVQAAFVKLKQLCVNEPF 358
Cdd:cd14593    1 RRIPLWCWNHPNGSALVRMANIKDLLQQRKIDQRICNAITRSHPLRSDVYKSDLDKTLPNIQEIQAAFVKLKQLCVNEPF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 359 EETEEKWLSSLENTRWLEYVRAFLKHSAELVYMLESKHLSVVLQEEEGRDLSCCVASLVQVMLDPYFRTITGFQSLIQKE 438
Cdd:cd14593   81 EETEEKWLSSLESTRWLEYVRAFLKHSAELVYMLESKHVSVILQEEEGRDLSCVVASLVQVMLDPYFRTITGFQSLIQKE 160

                        170       180       190
                 ....*....|....*....|....*....|....*
gi 767984582 439 WVMAGYQFLDRCNHLKRS-EKESPLFLLFLDATWQ 472
Cdd:cd14593  161 WVMAGYRFLDRCNHLKKSsKKESPLFLLFLDCVWQ 195
PH-GRAM_MTMR10 cd13346
Myotubularian (MTM) related 10 protein (MTMR10) Pleckstrin Homology-Glucosyltransferases, ...
 21-195 8.32e-136

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: 390.83  E-value: 8.32e-136
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582  21 TDDKINSEPKIKKLEPVLLPGEIVVNEVNFVRKCIATDTSQYDLWGKLICSNFKISFITDDPMPLQKFHYRNLLLGEHDV 100
Cdd:cd13346    1 TDDKINSEPKIKKLEPVLLPGEIVVNEVNFVRKCIATDTSQYDLWGKLICTNFKISFITDDPMPLQKFHYKNLLLGEHDV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 101 PLTCIEQIVTVNDHKRKQKVLGPNQKLKFNPTELIIYCKDFRIVRFRFDESGPESAKKVCLAIAHYSQPTDLQLLFAFEY 180
Cdd:cd13346   81 PLTCIEQIVTVNDTKRKQKVLGPNQKLKFNPTELIIYCKDFRIVRFRFDEAGPESAKKVCLAIAHYSQPTDLQLLFAFEY 160

                        170
                 ....*....|....*
gi 767984582 181 VGKKYHNSANKINGI 195
Cdd:cd13346  161 VGKKYHNSAGKVNGI 175
PTP-MTMR10-like cd14537
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 279-472 1.88e-107

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: 319.29  E-value: 1.88e-107
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 279 RRMPLWCWSHSNGSALVRMALIKDVLQQRKIDQRICNAITKSHPQRSDVYKSDLDKTLPNIQEVQAAFVKLKQLCVNEPF 358
Cdd:cd14537    1 GRPPVWCWSHPNGAALVRMAELLPTITDRTQENKMLEAIRKSHPNLKKPKVIDLDKLLPSLQDVQAAYLKLRELCTPDSS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 359 EETEE---KWLSSLENTRWLEYVRAFLKHSAELVYMLESKHLSVVLQEEEGRDLSCCVASLVQVMLDPYFRTITGFQSLI 435
Cdd:cd14537   81 EQFWVqdsKWYSLLENTKWLHYVSACLKKASEAAEALESRGRSVVLQESDGRDLSCVVSSLVQLLLDPHFRTITGFQSLI 160

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|
gi 767984582 436 QKEWVMAGYQFLDRCNHL---KRSEKESPLFLLFLDATWQ 472
Cdd:cd14537  161 QKEWVALGHPFCDRLGHVkpnKTESEESPVFLLFLDCVWQ 200
PH-GRAM_MTMR10-like cd13212
Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins ...
 39-164 8.42e-73

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: 227.50  E-value: 8.42e-73
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582  39 LPGEIVVNEVNFVRKCIATDTSQYDLWGKLICSNFKISFITDDPMPLQKFHYRNLLLGEHDVPLTCIEQIVTVNDHKRKQ 118
Cdd:cd13212    1 LPGEQVLAEAPGVRKGLQEDSSQPELSGTLICTNFKITFQPDDWQWLDNTQQKNPLNGEYDFALVCIGQIEAVSDLKRVQ 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*.
gi 767984582 119 KvLGPNQKLKFNPTELIIYCKDFRIVRFRFDESGPESAKKVCLAIA 164
Cdd:cd13212   81 L-LRPGSLLKFIPEELIIHCKDFRVLRFGFEATGGEEPKAFQVTIA 125
PTP-MTM-like cd14507
protein tyrosine phosphatase-like domain of myotubularins; Myotubularins are a unique subgroup ...
 279-472 1.36e-72

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: 230.51  E-value: 1.36e-72
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 279 RRMPLWCWSHS-NGSALVRMALIKDVLQQR--KIDQRICNAITKSHPQRSDVYKSDLDKTL------------------- 336
Cdd:cd14507    1 GRIPVLSWRHPrNGAVICRSSQPLVGLTGSrsKEDEKLLNAIRKASPSSKKLYIVDARPKLnavanrakgggyenteyyp 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 337 ---------PNIQEVQAAFVKLKQLCvnEPFEETEEKWLSSLENTRWLEYVRAFLKHSAELVYMLESKHLSVVLQEEEGR 407
Cdd:cd14507   81 nceleflniENIHAMRDSLNKLRDAC--LSPNDEESNWLSALESSGWLEHIRLILKGAVRVADLLEKEGTSVLVHCSDGW 158

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767984582 408 DLSCCVASLVQVMLDPYFRTITGFQSLIQKEWVMAGYQFLDRCNHLKR---SEKESPLFLLFLDATWQ 472
Cdd:cd14507  159 DRTSQLTSLAQLLLDPYYRTIEGFQVLIEKEWLSFGHKFADRCGHGDKnssDEERSPIFLQFLDCVWQ 226
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
 226-512 1.01e-69

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: 226.59  E-value: 1.01e-69
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582  226 DWDREIKRTGA---SGWRVCSINEGYMISTCLPEYIVVPSSLADQDLKIFSHSFVGRRMPLWCWSH-SNGSALVRMA--L 299
Cdd:pfam06602   9 DPEAEFARQGLpskDEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHkENGAVITRSSqpL 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582  300 IkDVLQQRKI-DQRICNAITKSHPQRS----------------------------DVYKSD----LDktLPNIQEVQAAF 346
Cdd:pfam06602  89 V-GLNGKRSIeDEKLLQAIFKSSNPYSakklyivdarpklnamanrakgggyeneDNYPNCkkifLG--IENIHVMRDSL 165

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582  347 VKLKQLCvnEPFEETEEKWLSSLENTRWLEYVRAFLKHSAELVYMLESKHLSVVLQEEEGRDLSCCVASLVQVMLDPYFR 426
Cdd:pfam06602 166 NKLVEAC--NDRSPSMDKWLSRLESSGWLKHIKAILDGACLIAQAVDLEGSSVLVHCSDGWDRTAQLTSLAQLLLDPYYR 243

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582  427 TITGFQSLIQKEWVMAGYQFLDRCNHL---KRSEKESPLFLLFLDATWQLLEQYPAAFEFSETYLAVLYDSTRISLFGTF 503
Cdd:pfam06602 244 TIEGFQVLIEKEWLSFGHKFADRCGHLagfTDSKERSPVFLQFLDCVWQLLRQFPCAFEFNERFLIRLLYHLYSCQFGTF 323


                  ....*....
gi 767984582  504 LFNSPHQRV 512
Cdd:pfam06602 324 LCNSEKERV 332
PTP-MTMR12 cd14594
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 279-473 7.26e-69

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: 220.10  E-value: 7.26e-69
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 279 RRMPLWCWSHSNGSALVRM-ALIKDV------LQQRKIDqRICNAITKSHPQRsdVYKSDLDKTLPNIQEVQAAFVKLKQ 351
Cdd:cd14594    1 RGIPIWCWSCHNGCALLKMsALPKEQddvalqDQKSFLD-RIYKTLSRPPYES--VKTEDLSASLPSLQEIQTAYNRFKQ 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 352 LCVNE---PFEETEEKWLSSLENTRWLEYVRAFLKHSAELVYMLESKHLSVVLQEEEGRDLSCCVASLVQVMLDPYFRTI 428
Cdd:cd14594   78 LFLIDnstDFWDTDVKWFSSLESSNWLEIIRQCLKKAVEVVECLEKQNTNVLLTEEEATDLCCVISSLVQIMMDPYCRTK 157

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*.
gi 767984582 429 TGFQSLIQKEWVMAGYQFLDRCNHLKRSEK-ESPLFLLFLDATWQL 473
Cdd:cd14594  158 SGFQSLIQKEWVMGGHCFLDRCNHLRQNDKeEVPVFLLFLDCVWQL 203
PTP-MTMR11 cd14595
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 279-473 8.95e-63

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: 203.91  E-value: 8.95e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 279 RRMPLWCWSHSNGSALVRMALIKDVLQQRKIDQRICNAITKSHpqRSDVYKSDLDKTLPNIQEVQAAFVKLKQLCVNEP- 357
Cdd:cd14595    1 GRIPRWCWHHPGGSDLLRMAGFYTNSDPEKEDIRSVELLLQAG--HSQCVIVDTSEELPSPADIQLAYLKLRTLCLPDIs 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 358 FEETEEKWLSSLENTRWLEYVRAFLKHSAELVYMLESKHLSVVLQEEEGRDLSCCVASLVQVMLDPYFRTITGFQSLIQK 437
Cdd:cd14595   79 VSVSDEKWLSNLEGTRWLDHVRACLRKASEVSCLLAERHRSVILQESEDRDLNCLLSSLVQLLSDPHARTISGFQSLVQK 158

                        170       180       190
                 ....*....|....*....|....*....|....*..
gi 767984582 438 EWVMAGYQFLDRCNHLKRSEK-ESPLFLLFLDATWQL 473
Cdd:cd14595  159 EWVVAGHPFLQRLNLTRESDKeESPVFLLFLDCVWQL 195
PTP-MTMR6-like cd14532
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases ...
 227-493 2.56e-47

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: 166.75  E-value: 2.56e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 227 WDREIKRTGA--SGWRVCSINEGYMISTCLPEYIVVPSSlADQDLKIFSHSFVGR-RMPLWCWSH-SNGSALVRMALIKD 302
Cdd:cd14532    1 LESEYTRMGVpnDNWTLSDINKDYELCDTYPRELFVPTS-ASTPVLVGSSKFRSKgRLPVLSYLHkDNQAAICRCSQPLS 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 303 VLQQRKI-DQRICNAITKSHPQRSDVYKSDldkTLP-------------------------------NIQEVQAAFVKLK 350
Cdd:cd14532   80 GFSARCVeDEQLLQAIRKANPNSKFMYVVD---TRPkinamankaagkgyenednysnikfqffgieNIHVMRSSLQKLL 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 351 QLCvnEPFEETEEKWLSSLENTRWLEYVRAFLKHSAELVYMLESKHlSVVLQEEEGRDLSCCVASLVQVMLDPYFRTITG 430
Cdd:cd14532  157 EVC--ELKNPSMSAFLSGLESSGWLKHIKAVMDTSVFIAKAVSEGA-SVLVHCSDGWDRTAQTCSLASLLLDPYYRTIKG 233

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767984582 431 FQSLIQKEWVMAGYQFLDRCNHLKRSEKE-SPLFLLFLDATWQLLEQYPAAFEFSETYLAVLYD 493
Cdd:cd14532  234 FQVLIEKEWLSFGHKFTDRCGHLQGDAKEvSPVFTQFLDCVWQLMQQFPRAFEFNERFLLTLHD 297
PTP-MTMR5-like cd14534
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 239-476 3.71e-41

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: 149.44  E-value: 3.71e-41
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 239 WRVCSINEGYMISTCLPEYIVVPSSLADQDLKIFSHSFVGRRMPLWCWSHSNGSA-LVRMALI--KDVLQQRKIDQRICN 315
Cdd:cd14534    1 FRISTANRDYSICRSYPALVVVPQSVSDESLRKVARCYRQGRFPVVTWRHPRTKAlLLRSGGFhgKGVMGMLKSANTSTS 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 316 AITKSHPQRSDV-----YKSDL------DKT-------------------LPNIQEVQAAFVKLKQLCVNEPF-EETEEK 364
Cdd:cd14534   81 SPTVSSSETSSSleqekYLSALvlyvlgEKSqmkgvkaesdpkcefipveYPEVRQVKASFKKLLRACVPSSApTEPEQS 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 365 WLSSLENTRWLEYVRAFLKHSAELVYMLESKHLSVVLQEEEGRDLSCCVASLVQVMLDPYFRTITGFQSLIQKEWVMAGY 444
Cdd:cd14534  161 FLKAVEDSEWLQQLQCLMQLSGAVVDLLDVQGSSVLLCLEDGWDVTTQVSSLSQLLLDPYYRTLEGFRVLVEKEWLAFGH 240

                        250       260       270
                 ....*....|....*....|....*....|....
gi 767984582 445 QFLDRCNHLKRSEKE--SPLFLLFLDATWQLLEQ 476
Cdd:cd14534  241 RFSHRSNLTAASQSSgfAPVFLQFLDAVHQIHRQ 274
PTP-MTM1-like cd14535
protein tyrosine phosphatase-like domain of myotubularin, and myotubularin related ...
 338-493 2.65e-35

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: 132.57  E-value: 2.65e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 338 NIQEVQAAFVKLKQLCvnepFEETEE-KWLSSLENTRWLEYVRAFLKHSAELVYMLESKHLSVVLQEEEGRDLSCCVASL 416
Cdd:cd14535   91 NIHVMRESLRKLKDIC----FPNIDDsHWLSNLESTHWLEHIKLILAGAVRIADKVESGKTSVVVHCSDGWDRTAQLTSL 166

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 417 VQVMLDPYFRTITGFQSLIQKEWVMAGYQFLDRCNHLKRSEKE---SPLFLLFLDATWQLLEQYPAAFEFSETYLAVLYD 493
Cdd:cd14535  167 AMLMLDPYYRTIRGFEVLIEKEWLSFGHKFAQRIGHGDKNHSDadrSPVFLQFIDCVWQMTRQFPNAFEFNEHFLITILD 246
PTP-MTMR8 cd14584
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 226-493 2.94e-35

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: 134.23  E-value: 2.94e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 226 DWDREIKRTGASG--WRVCSINEGYMISTCLPEYIVVPSSlADQDLKIFSHSFVGR-RMPLWCWSHS-NGSALVRMALIK 301
Cdd:cd14584    6 DLKVDFQRMGIPNdyWEITDANKNYEICSTYPPELVVPKS-ASKATVVGSSKFRSRgRFPVLSYLYKeNNAAICRCSQPL 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 302 DVLQQRKI-DQRICNAITKSHPQRSDVYKSDLDKTL----------------------------PNIQEVQAAFVKLKQL 352
Cdd:cd14584   85 SGFSARCVeDEQMLQAISKANPGSPFMYVVDTRPKLnamanraagkgyenednysnirfqfigiENIHVMRSSLQKLLEV 164

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 353 CvnEPFEETEEKWLSSLENTRWLEYVRAFLKHSAELVYMLESKHLSVVLQEEEGRDLSCCVASLVQVMLDPYFRTITGFQ 432
Cdd:cd14584  165 C--EMKSPSMSDFLTGLENSGWLRHIKAVMDAGVFLAKAVKEEKASVLVHCSDGWDRTAQVCSLASLLLDPFYRTIKGLM 242

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 767984582 433 SLIQKEWVMAGYQFLDRCNHLKRSEKE-SPLFLLFLDATWQLLEQYPAAFEFSETYLAVLYD 493
Cdd:cd14584  243 VLIEKEWISMGHKFSQRCGHLDGDPKEvSPVFTQFLECVWQLMEQFPCAFEFNEHFLLEIHD 304
PTP-MTMR2 cd14590
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 266-493 5.56e-35

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: 132.08  E-value: 5.56e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 266 DQDLKIFShSFVGR-RMPLWCWSHSNGSALV---RMALIKDVLQQRKIDQRICNAITKSHPQRSDVYKSD---------- 331
Cdd:cd14590    1 DEELKRVA-SFRSRgRIPVLSWIHPESQATItrcSQPMVGVSGKRSKEDEKYLQAIMDSNAQSHKIFIFDarpsvnavan 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 332 --------------------LDktLPNIQEVQAAFVKLKQLcVNEPFEETEekWLSSLENTRWLEYVRAFLKHSAELVYM 391
Cdd:cd14590   80 kakgggyesedayqnaelvfLD--IHNIHVMRESLRKLKEI-VYPNIEESH--WLSNLESTHWLEHIKLILAGALRIADK 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 392 LESKHLSVVLQEEEGRDLSCCVASLVQVMLDPYFRTITGFQSLIQKEWVMAGYQFLDRCNHLKRSEKE---SPLFLLFLD 468
Cdd:cd14590  155 VESGKTSVVVHCSDGWDRTAQLTSLAMLMLDGYYRTIRGFEVLVEKEWLSFGHRFQLRVGHGDKNHADadrSPVFLQFID 234

                        250       260
                 ....*....|....*....|....*
gi 767984582 469 ATWQLLEQYPAAFEFSETYLAVLYD 493
Cdd:cd14590  235 CVWQMTRQFPTAFEFNEYFLITILD 259
PH-GRAM_MTMR12 cd13348
Myotubularian (MTM) related 12 protein (MTMR12) Pleckstrin Homology-Glucosyltransferases, ...
 19-180 7.72e-35

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: 129.20  E-value: 7.72e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582  19 PQTDDKINSEPKIKKLEPVLLPGEIVVNEVNFVRKCIATDTSQYDLWGKLICSNFKISFITDDPMPLQ-KFHYRNLLLGE 97
Cdd:cd13348    1 TEEEIKLEKEPQEKEVNPHLLPGEVVLCEANTVLKYTQDDGSQRGVYGRLVCTNFRIAFLGDDAPQDDnSKQFKNKIYGE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582  98 HDVPLTCIEQIVTVNDHKRkqKVLGPNQKLKFNPTELIIYCKDFRIVRFRFDESGPESAKKVCLAIAHYSQ-PTDLQLLF 176
Cdd:cd13348   81 NDITLQCVDQIYGVYDEKK--KLITGGLVKNKYPEKLIIHCKDLRVFQFCLRYTKEEEVKRIVSGIIHHTQePKLLKRLF 158


                 ....
gi 767984582 177 AFEY 180
Cdd:cd13348  159 LFSY 162
PTP-MTM1 cd14591
protein tyrosine phosphatase-like domain of myotubularin phosphoinositide phosphatase 1; ...
 280-493 7.75e-35

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: 131.30  E-value: 7.75e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 280 RMPLWCWSH-SNGSALVRMA--LIKDVLQQRKIDQRICNAITKSHPQRSDV--------------------YKSD----- 331
Cdd:cd14591    2 RIPVLSWIHpENQAVIMRCSqpLVGMSGKRNKDDEKYLDIIREANGQTSKLtiydarpsvnavankatgggYEGDdayqn 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 332 -----LDktLPNIQEVQAAFVKLKQLcVNEPFEETEekWLSSLENTRWLEYVRAFLKHSAELVYMLESKHLSVVLQEEEG 406
Cdd:cd14591   82 aelvfLD--IHNIHVMRESLKKLKDI-VYPNVEESH--WLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDG 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 407 RDLSCCVASLVQVMLDPYFRTITGFQSLIQKEWVMAGYQFLDRCNHLKRSEKE---SPLFLLFLDATWQLLEQYPAAFEF 483
Cdd:cd14591  157 WDRTAQLTSLAMLMLDSYYRTIEGFEVLVQKEWISFGHKFASRIGHGDKNHADadrSPIFLQFIDCVWQMSKQFPTAFEF 236

                        250
                 ....*....|
gi 767984582 484 SETYLAVLYD 493
Cdd:cd14591  237 NEQFLITILD 246
PTP-MTMR6 cd14585
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 230-493 8.46e-35

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: 132.75  E-value: 8.46e-35
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 230 EIKRTGA--SGWRVCSINEGYMISTCLPEYIVVPSSlADQDLKIFSHSFVGR-RMPLWCWSH-SNGSALVRMALIKDVLQ 305
Cdd:cd14585    4 EYKRMGVpnDYWQLSDVNRDYKICDTYPRDLYVPIT-ASKPIIVGSSKFRSKgRFPVLSYYHqEKKAAICRCSQPLSGFS 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 306 QRKI-DQRICNAITKSHPQRSDVYKSDLDKTL----------------------------PNIQEVQAAFVKLKQLCVNE 356
Cdd:cd14585   83 ARCLeDEHMLQAISKANPNNRYMYVMDTRPKLnamanraagkgyenednysnirfqfvgiENIHVMRSSLQKLLEVCGTK 162

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 357 PFEETEekWLSSLENTRWLEYVRAFLKHSAELVYMLESKHLSVVLQEEEGRDLSCCVASLVQVMLDPYFRTITGFQSLIQ 436
Cdd:cd14585  163 ALSVND--FLSGLESSGWLRHIKAVLDAAVFLAKAVAVEGASVLVHCSDGWDRTAQVCSLGSLLLDPYYRTIKGFMVLIE 240

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 767984582 437 KEWVMAGYQFLDRCNHLKRSEKE-SPLFLLFLDATWQLLEQYPAAFEFSETYLAVLYD 493
Cdd:cd14585  241 KDWISFGHKFSDRCGQLDGDPKEiSPVFTQFLECVWQLTEQFPRAFEFSEAFLLQIHE 298
PTP-MTMR1 cd14592
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 336-493 1.20e-34

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: 130.87  E-value: 1.20e-34
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 336 LPNIQEVQAAFVKLKQLcVNEPFEETeeKWLSSLENTRWLEYVRAFLKHSAELVYMLESKHLSVVLQEEEGRDLSCCVAS 415
Cdd:cd14592   89 IHNIHVMRESLRKLKEI-VYPSIDEA--RWLSNVDGTHWLEYIRMLLAGAVRIADKIESGKTSVVVHCSDGWDRTAQLTS 165

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 416 LVQVMLDPYFRTITGFQSLIQKEWVMAGYQFLDRCNHLKRSEKE---SPLFLLFLDATWQLLEQYPAAFEFSETYLAVLY 492
Cdd:cd14592  166 LAMLMLDSYYRTIKGFEVLIEKEWISFGHRFALRVGHGDDNHADadrSPIFLQFIDCVWQMTRQFPSAFEFNELFLITIL 245


                 .
gi 767984582 493 D 493
Cdd:cd14592  246 D 246
PTP-MTMR9 cd14536
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 334-472 5.03e-33

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: 125.53  E-value: 5.03e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 334 KTLPNIQEVQAAFVKLKQLCVNEpfEETEEKWLSSLENTRWLEYVRAFLKHSAELVYMLESKHLSVVLQEEEGRDLSCCV 413
Cdd:cd14536   84 KPIERYNVLQESLIKLVEACNDQ--GHSMDKWLSKLESSNWLSHVKEILTTACLVAQCIDREGASVLVHGSEGMDSTLQV 161

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767984582 414 ASLVQVMLDPYFRTITGFQSLIQKEWVMAGYQFLDRCNHL----KRSEKESPLFLLFLDATWQ 472
Cdd:cd14536  162 TSLAQIILDPDCRTIRGFEALIEREWLQAGHPFQSRCAKSaysnSKQKFESPVFLLFLDCVWQ 224
PTP-MTMR7 cd14583
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 230-488 2.67e-30

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: 120.06  E-value: 2.67e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 230 EIKRTG--ASGWRVCSINEGYMISTCLPEYIVVPSSlADQDLKIFSHSFVGR-RMP-LWCWSHSNGSALVRMALIKDVLQ 305
Cdd:cd14583    4 EYNRMGlpNSLWQVSDVNRDYRVCDTYPTELYVPKS-ATAPIIVGSSKFRSRgRFPvLSYYCKDNNASICRSSQPLSGFS 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 306 QRKI-DQRICNAITKSHPQRSDVYKSDLDKTL----------------------------PNIQEVQAAFVKLKQLCvnE 356
Cdd:cd14583   83 ARCLeDEQMLQAIRKANPGSDFMYVVDTRPKLnamanraagkgyenednysnikfqfigiENIHVMRNSLQKMLEVC--E 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 357 PFEETEEKWLSSLENTRWLEYVRAFLKHSAELVYMLESKHLSVVLQEEEGRDLSCCVASLVQVMLDPYFRTITGFQSLIQ 436
Cdd:cd14583  161 LRSPSMGDFLWGLENSGWLKHIKAIMDAGIFIAKAVAEEGASVLVHCSDGWDRTAQVCSVASLLLDPYYRTIKGFMVLIE 240

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767984582 437 KEWVMAGYQFLDRCNHLKRSEKE-SPLFLLFLDATWQLLEQYPAAFEFSETYL 488
Cdd:cd14583  241 KDWVSFGHKFNHRYGHLDGDPKEvSPVIDQFIECVWQLMEQFPCAFEFNERFL 293
PTP-MTMR3 cd14586
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 237-472 1.43e-29

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: 118.59  E-value: 1.43e-29
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 237 SGWRVCSINEGYMISTCLPEYIVVPSSLADQDLKIFSHSFVGRRMPLWCWSH-SNGSALVRMA----------------L 299
Cdd:cd14586    6 NAWRISNINEKYKLCGSYPQELIVPAWITDKELESVASFRSWKRIPAVVYRHqSNGAVIARCGqpevswwgwrnaddehL 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 300 IKDVLQQRKIDQRICNAI------TKSHPQRSDVYKSDLDKTLPNIQEVQA----------------------------- 344
Cdd:cd14586   86 VQSVAKACASDSSSCKSVlmtgncSRDFPNGGDLSDVEFDSSMSNASGVESlaiqpqkllildarsyaaavanrakgggc 165

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 345 ------------------------AFVKLKQLCVNEPfeeTEEKWLSSLENTRWLEYVRAFLKHSAELVYMLESKHLSVV 400
Cdd:cd14586  166 ecpeyypncevvfmgmanihsirkSFQSLRLLCTQMP---DPANWLSALESTKWLQHLSMLLKSALLVVHAVDRDQRPVL 242

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767984582 401 LQEEEGRDLSCCVASLVQVMLDPYFRTITGFQSLIQKEWVMAGYQFLDRCNHLKRSE---KESPLFLLFLDATWQ 472
Cdd:cd14586  243 VHCSDGWDRTPQIVALSKLLLDPYYRTIEGFQVLVETEWLDFGHKFADRCGHGENSDdlnERCPVFLQWLDCVHQ 317
PH-GRAM_MTMR11 cd15790
Myotubularian (MTM) related 11 protein (MTMR11) Pleckstrin Homology-Glucosyltransferases, ...
 39-154 1.17e-28

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: 110.25  E-value: 1.17e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582  39 LPGEIVVNEVNFVRKCIATDTSQYDLWGKLICSNFKISFITDDPmPLQKFHYRNLLLGEHDVPLTCIEQIVTVNDhKRKQ 118
Cdd:cd15790    1 LPGEHILEEAVRVRKLVQWRDGEGFLSGTLYCTNFRVAFVPEHI-QKDENDHDTVLNSEHDIALPSIDRVVAVQG-PTTM 78

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 767984582 119 KVLGPNQKLKFNPTELIIYCKDFRIVRFRFDESGPE 154
Cdd:cd15790   79 KAVTASSGLKFIPEELVIYCRDFRLLRFQFEQSTLE 114
PTP-MTMR3-like cd14533
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases ...
 336-472 2.47e-28

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: 112.50  E-value: 2.47e-28
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 336 LPNIQEVQAAFVKLKQLCVNEPFEETeekWLSSLENTRWLEYVRAFLKHSAELVYMLESKHLSVVLQEEEGRDLSCCVAS 415
Cdd:cd14533   93 LANIHAIRKSFHSLRALCSSAPDQPN---WLSNLESTKWLHHLSGLLKAALLVVNAVDEEGRPVLVHCSDGWDRTPQIVA 169

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 416 LVQVMLDPYFRTITGFQSLIQKEWVMAGYQFLDRCNHLKRSE---KESPLFLLFLDATWQ 472
Cdd:cd14533  170 LAELMLDPYYRTIEGFQVLVEREWLDFGHKFADRCGHGVNSEdinERCPVFLQWLDCVHQ 229
PTP-MTMR13 cd14589
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 239-476 1.84e-25

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: 106.54  E-value: 1.84e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 239 WRVCSINEGYMISTCLPEYIVVPSSLADQDLKIFSHSFVGRRMPLWCWSHS-NGSALVR---------MALIKD------ 302
Cdd:cd14589    1 FRITAVNRMYSLCRSYPGLLVVPQSVQDSSLQKVARCYRHNRLPVVCWKNSkTKAVLLRsggfhgkgvVGLFKSqnphsa 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 303 ---------VLQQRKIDQRICNAITKSHP-----------------------QRSDVYKSDLDKTL---------PNIQE 341
Cdd:cd14589   81 apassesssSIEQEKYLQALLNAISVHQKmngnstllqsqllkrqaalyifgEKSQLRGFKLDFALncefvpvefHDIRQ 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 342 VQAAFVKLKQLCVNEPF-EETEEKWLSSLENTRWLEYVRAFLKHSAELVYMLESKHlSVVLQEEEGRDLSCCVASLVQVM 420
Cdd:cd14589  161 VKASFKKLMRACVPSTIpTDSEVTFLKALGESEWFLQLHRIMQLAVVISELLESGS-SVMVCLEDGWDITTQVVSLVQLL 239

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 767984582 421 LDPYFRTITGFQSLIQKEWVMAGYQFLDRCNHLKRSEKE--SPLFLLFLDATWQLLEQ 476
Cdd:cd14589  240 SDPFYRTLEGFQMLVEKEWLSFGHKFSQRSNLTPNSQGSgfAPIFLQFLDCVHQIHNQ 297
PTP-MTMR5 cd14588
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 239-473 2.15e-25

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: 106.21  E-value: 2.15e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 239 WRVCSINEGYMISTCLPEYIVVPSSLADQDLKIFSHSFVGRRMPLWCWSHSNGSA-LVRMA---------LIKD------ 302
Cdd:cd14588    1 FRISTVNRMYAVCRSYPGLLIVPQSIQDNTIQRISRCYRQNRFPVVCWRNSRTKAvLLRSGglhgkgvvgLFKSqnapaa 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 303 --------VLQQRKIDQricnAITKSHPQRSDVY-----------------KSDLDKTLPN--------------IQEVQ 343
Cdd:cd14588   81 gqsqtdstSLEQEKYLQ----AVINSMPRYADASgrntlsgfraalyiigdKSQLKGVKQDplqqwevvpievfdVRQVK 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 344 AAFVKLKQLCV-NEPFEETEEKWLSSLENTRWLEYVRAFLKHSAELVYMLESKHlSVVLQEEEGRDLSCCVASLVQVMLD 422
Cdd:cd14588  157 ASFKKLMKACVpSCPSTDPSQTYLRTLEESEWLSQLHKLLQVSVLVVELLDSGS-SVLVSLEDGWDITTQVVSLVQLLSD 235

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|...
gi 767984582 423 PYFRTITGFQSLIQKEWVMAGYQFLDRCNHLKRSEKE--SPLFLLFLDATWQL 473
Cdd:cd14588  236 PYYRTIEGFRLLVEKEWLSFGHRFSHRGAQTLASQSSgfTPVFLQFLDCVHQI 288
PTP-MTMR4 cd14587
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 239-472 5.08e-25

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: 105.50  E-value: 5.08e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 239 WRVCSINEGYMISTCLPEYIVVPSSLADQDLKIFSHSFVGRRMPLWCWSHS-NGSALVRMAlikdvlqQRKI-------- 309
Cdd:cd14587    3 WRVSEINSNYKLCSSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLrNGAVIARCS-------QPEIswwgwrna 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 310 -DQRICNAITKS-----------------HPQRSDVYKSDLDKTL----------------------------------- 336
Cdd:cd14587   76 dDEYLVTSIAKAcaldpgtrapggspskgNSDGSDASDTDFDSSLtacsavesgaapqkllildarsytaavanrakggg 155

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 337 -----------------PNIQEVQAAFVKLKQLCVNEPfeeTEEKWLSSLENTRWLEYVRAFLKHSAELVYMLESKHLSV 399
Cdd:cd14587  156 ceceeyypncevmfmgmANIHSIRNSFQYLRAVCSQMP---DPGNWLSALESTKWLQHLSVMLKAAVLVASAVDREGRPV 232

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767984582 400 VLQEEEGRDLSCCVASLVQVMLDPYFRTITGFQSLIQKEWVMAGYQFLDRCNHLKRSEKES---PLFLLFLDATWQ 472
Cdd:cd14587  233 LVHCSDGWDRTPQIVALAKILLDPYYRTIEGFQVLVETDWLDFGHKFGDRCGHQENVEDQNeqcPVFLQWLDCVHQ 308
PTP-MTM-like_fungal cd17666
protein tyrosine phosphatase-like domain of fungal myotubularins; Myotubularins are a unique ...
 352-472 9.04e-21

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: 90.97  E-value: 9.04e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582 352 LCVNEPFEETEEKWLSSLENTRWLEYVRAFLKHSAELVYMLESKHLSVVLQEEEGRDLSCCVASLVQVMLDPYFRTITGF 431
Cdd:cd17666  113 LKDGDDSNPSYPPLINALKKSNWLKYLAIILQGADLIAKSIHFNHSHVLIHCSDGWDRTSQLSALAQLCLDPYYRTLEGF 192

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 767984582 432 QSLIQKEWVMAGYQFLDRCNHlkrseKE-SPLFLLFLDATWQ 472
Cdd:cd17666  193 MVLVEKDWLSFGHRFAERSGH-----KEtSPVFHQFLDCVYQ 229
PH-GRAM cd10570
Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins ...
 46-163 4.43e-14

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


Pssm-ID: 275393  Cd Length: 94  Bit Score: 67.79  E-value: 4.43e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582  46 NEVNFVRKCIATDTSQYDLWGKLICSNFKISFITDDPMPLQKFhyrnlllgehDVPLTCIEQivtVNDHKRKQkvlgpnq 125
Cdd:cd10570    1 IEKLGVRFCCALRPRKLPLEGTLYLSTYRLIFSSKADGDETKL----------VIPLVDITD---VEKIAGAS------- 60

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 767984582 126 klkFNPTELIIYCKDFRIVRFRFDeSGPESAKKVCLAI 163
Cdd:cd10570   61 ---FLPSGLIITCKDFRTIKFSFD-SEDEAVKVIARVL 94
PH-GRAM_MTM-like cd13223
Myotubularian 1 and related proteins Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase; ...
 66-169 6.91e-05

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


Pssm-ID: 275407  Cd Length: 100  Bit Score: 41.84  E-value: 6.91e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767984582  66 GKLICSNFKISFITDDPMPLQKFhyrnlllgehDVPLTCIEQIvtvndhkrkQKVLGPNQKlKFNPTELIIYCKDFRIVR 145
Cdd:cd13223   18 GTLYITNYRLYFKSRDREPNFVL----------DVPLGVISRV---------EKVGGATSR-GENSYGLEIHCKDMRNLR 77

                         90       100
                 ....*....|....*....|....
gi 767984582 146 FRFDESGpESAKKVCLAIAHYSQP 169
Cdd:cd13223   78 FAHKQEN-HSRRKLYETLQKYAFP 100
 
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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