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Conserved domains on  [gi|1869284176|ref|NP_001372163|]
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myotubularin-related protein 6 isoform 6 [Homo sapiens]

Protein Classification

protein-tyrosine phosphatase family protein; tyrosine-protein phosphatase( domain architecture ID 12988791)

cys-based protein-tyrosine phosphatase (PTP) family protein may be a PTP or a dual-specificity phosphatase (DUSP or DSP), and may catalyze the dephosphorylation of target phosphoproteins at tyrosine or tyrosine and serine/threonine residues, respectively; similar to Mus musculus myotubularin-related protein 14 (MTMR14) which is a phosphoinositide phosphatase which specifically dephosphorylates PtdIns(3,5)P2) and PI3P; contains a pleckstrin homology-like (PH-like) domain; tyrosine-protein phosphatase catalyzes the dephosphorylation of O-phosphotyrosine groups in phosphoproteins; has a C-terminal GNAT-family acetyltransferase domain

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PTP_DSP_cys super family cl28904
cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This ...
 130-386 0e+00

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


The actual alignment was detected with superfamily member cd14585:

Pssm-ID: 475123 [Multi-domain]  Cd Length: 302  Bit Score: 549.53  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 130 LAEEYKRMGVPNSHWQLSDANRDYKICETYPRELYVPRIASKPIIVGSSKFRSKGRFPVLSYYHQDKE------------ 197
Cdd:cd14585     1 LAEEYKRMGVPNDYWQLSDVNRDYKICDTYPRDLYVPITASKPIIVGSSKFRSKGRFPVLSYYHQEKKaaicrcsqplsg 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 198 ---------------------------------LNAMANRAAGKGYENEDNYSNIRFQFVGIENIHVMRSSLQKLLEVNG 244
Cdd:cd14585    81 fsarcledehmlqaiskanpnnrymyvmdtrpkLNAMANRAAGKGYENEDNYSNIRFQFVGIENIHVMRSSLQKLLEVCG 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 245 TKGLSVNDFYSGLESSGWLRHIKAVMDAAIFLAKAITVENASVLVHCSDGWDRTSQVCSLGSLLLDSYYRTIKGFMVLIE 324
Cdd:cd14585   161 TKALSVNDFLSGLESSGWLRHIKAVLDAAVFLAKAVAVEGASVLVHCSDGWDRTAQVCSLGSLLLDPYYRTIKGFMVLIE 240

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1869284176 325 KDWISFGHKFSERCGQLDGDPKEVSPVFTQFLECVWHLTEQFPQAFEFSEAFLLQIHEHIHS 386
Cdd:cd14585   241 KDWISFGHKFSDRCGQLDGDPKEISPVFTQFLECVWQLTEQFPRAFEFSEAFLLQIHEHIHS 302
PH-GRAM_MTMR6 cd13343
Myotubularian (MTM) related (MTMR) 6 protein Pleckstrin Homology-Glucosyltransferases, ...
 1-101 1.94e-68

Myotubularian (MTM) related (MTMR) 6 protein Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR6 is a member of the myotubularin dual specificity protein phosphatase gene family. MTMR6 binds to phosphoinositide lipids through its PH-GRAM domain. It acts as a negative regulator of KCNN4/KCa3.1 channel activity in CD4+ T-cells possibly by decreasing intracellular levels of phosphatidylinositol-3 phosphatase and negatively regulates proliferation of reactivated CD4+ T-cells MTMR6 interacts with MTMR7, MTMR8 and MTMR9. MTMR6 contains a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an active PTP domain, a SET-interaction domain, and a C-terminal coiled-coil region. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 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: 270151  Cd Length: 101  Bit Score: 216.42  E-value: 1.94e-68
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176   1 MEHIRTTKVEQVKLLDRFSTSNKSLTGTLYLTATHLLFIDSHQKETWILHHHIASVEKLALTTSGCPLVIQCKNFRTVHF 80
Cdd:cd13343     1 MEHIRTTKVEQVKLLDRFSTSNKSLTGTLYLTATHLLFIDNSQQETWILHHHIAPVEKLSLTTSGCPLVIQCKNFRVVHF 80

                          90       100
                  ....*....|....*....|.
gi 1869284176  81 IVPRERDCHDIYNSLLQLSKQ 101
Cdd:cd13343    81 VVPRERDCHDIYNSLLQLSRP 101
 
Name Accession Description Interval E-value
PTP-MTMR6 cd14585
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 130-386 0e+00

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: 549.53  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 130 LAEEYKRMGVPNSHWQLSDANRDYKICETYPRELYVPRIASKPIIVGSSKFRSKGRFPVLSYYHQDKE------------ 197
Cdd:cd14585     1 LAEEYKRMGVPNDYWQLSDVNRDYKICDTYPRDLYVPITASKPIIVGSSKFRSKGRFPVLSYYHQEKKaaicrcsqplsg 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 198 ---------------------------------LNAMANRAAGKGYENEDNYSNIRFQFVGIENIHVMRSSLQKLLEVNG 244
Cdd:cd14585    81 fsarcledehmlqaiskanpnnrymyvmdtrpkLNAMANRAAGKGYENEDNYSNIRFQFVGIENIHVMRSSLQKLLEVCG 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 245 TKGLSVNDFYSGLESSGWLRHIKAVMDAAIFLAKAITVENASVLVHCSDGWDRTSQVCSLGSLLLDSYYRTIKGFMVLIE 324
Cdd:cd14585   161 TKALSVNDFLSGLESSGWLRHIKAVLDAAVFLAKAVAVEGASVLVHCSDGWDRTAQVCSLGSLLLDPYYRTIKGFMVLIE 240

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1869284176 325 KDWISFGHKFSERCGQLDGDPKEVSPVFTQFLECVWHLTEQFPQAFEFSEAFLLQIHEHIHS 386
Cdd:cd14585   241 KDWISFGHKFSDRCGQLDGDPKEISPVFTQFLECVWQLTEQFPRAFEFSEAFLLQIHEHIHS 302
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
 123-400 5.72e-175

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: 497.77  E-value: 5.72e-175
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 123 QGWQLIDLAEEYKRMGVPN-SHWQLSDANRDYKICETYPRELYVPRIASKPIIVGSSKFRSKGRFPVLSYYH-------- 193
Cdd:pfam06602   3 NGWDLYDPEAEFARQGLPSkDEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHkengavit 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 194 ---------------QDKEL-------------------------NAMANRAAGKGYENEDNYSNIRFQFVGIENIHVMR 233
Cdd:pfam06602  83 rssqplvglngkrsiEDEKLlqaifkssnpysakklyivdarpklNAMANRAKGGGYENEDNYPNCKKIFLGIENIHVMR 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 234 SSLQKLLEVNGTKGLSVNDFYSGLESSGWLRHIKAVMDAAIFLAKAITVENASVLVHCSDGWDRTSQVCSLGSLLLDSYY 313
Cdd:pfam06602 163 DSLNKLVEACNDRSPSMDKWLSRLESSGWLKHIKAILDGACLIAQAVDLEGSSVLVHCSDGWDRTAQLTSLAQLLLDPYY 242

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 314 RTIKGFMVLIEKDWISFGHKFSERCGQLDG--DPKEVSPVFTQFLECVWHLTEQFPQAFEFSEAFLLQIHEHIHSCQFGN 391
Cdd:pfam06602 243 RTIEGFQVLIEKEWLSFGHKFADRCGHLAGftDSKERSPVFLQFLDCVWQLLRQFPCAFEFNERFLIRLLYHLYSCQFGT 322


                  ....*....
gi 1869284176 392 FLGNCQKER 400
Cdd:pfam06602 323 FLCNSEKER 331
PH-GRAM_MTMR6 cd13343
Myotubularian (MTM) related (MTMR) 6 protein Pleckstrin Homology-Glucosyltransferases, ...
 1-101 1.94e-68

Myotubularian (MTM) related (MTMR) 6 protein Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR6 is a member of the myotubularin dual specificity protein phosphatase gene family. MTMR6 binds to phosphoinositide lipids through its PH-GRAM domain. It acts as a negative regulator of KCNN4/KCa3.1 channel activity in CD4+ T-cells possibly by decreasing intracellular levels of phosphatidylinositol-3 phosphatase and negatively regulates proliferation of reactivated CD4+ T-cells MTMR6 interacts with MTMR7, MTMR8 and MTMR9. MTMR6 contains a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an active PTP domain, a SET-interaction domain, and a C-terminal coiled-coil region. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 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: 270151  Cd Length: 101  Bit Score: 216.42  E-value: 1.94e-68
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176   1 MEHIRTTKVEQVKLLDRFSTSNKSLTGTLYLTATHLLFIDSHQKETWILHHHIASVEKLALTTSGCPLVIQCKNFRTVHF 80
Cdd:cd13343     1 MEHIRTTKVEQVKLLDRFSTSNKSLTGTLYLTATHLLFIDNSQQETWILHHHIAPVEKLSLTTSGCPLVIQCKNFRVVHF 80

                          90       100
                  ....*....|....*....|.
gi 1869284176  81 IVPRERDCHDIYNSLLQLSKQ 101
Cdd:cd13343    81 VVPRERDCHDIYNSLLQLSRP 101
PTPc_motif smart00404
Protein tyrosine phosphatase, catalytic domain motif;
263-317 1.59e-05

Protein tyrosine phosphatase, catalytic domain motif;


Pssm-ID: 214649 [Multi-domain]  Cd Length: 105  Bit Score: 43.89  E-value: 1.59e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1869284176  263 LRHIKAVMDAaiflaKAITVENASVLVHCSDGWDRTSQVCSLGSLLLDSYYRTIK 317
Cdd:smart00404  23 LELLRAVKKN-----LNQSESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEAGE 72
 
Name Accession Description Interval E-value
PTP-MTMR6 cd14585
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 130-386 0e+00

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: 549.53  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 130 LAEEYKRMGVPNSHWQLSDANRDYKICETYPRELYVPRIASKPIIVGSSKFRSKGRFPVLSYYHQDKE------------ 197
Cdd:cd14585     1 LAEEYKRMGVPNDYWQLSDVNRDYKICDTYPRDLYVPITASKPIIVGSSKFRSKGRFPVLSYYHQEKKaaicrcsqplsg 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 198 ---------------------------------LNAMANRAAGKGYENEDNYSNIRFQFVGIENIHVMRSSLQKLLEVNG 244
Cdd:cd14585    81 fsarcledehmlqaiskanpnnrymyvmdtrpkLNAMANRAAGKGYENEDNYSNIRFQFVGIENIHVMRSSLQKLLEVCG 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 245 TKGLSVNDFYSGLESSGWLRHIKAVMDAAIFLAKAITVENASVLVHCSDGWDRTSQVCSLGSLLLDSYYRTIKGFMVLIE 324
Cdd:cd14585   161 TKALSVNDFLSGLESSGWLRHIKAVLDAAVFLAKAVAVEGASVLVHCSDGWDRTAQVCSLGSLLLDPYYRTIKGFMVLIE 240

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1869284176 325 KDWISFGHKFSERCGQLDGDPKEVSPVFTQFLECVWHLTEQFPQAFEFSEAFLLQIHEHIHS 386
Cdd:cd14585   241 KDWISFGHKFSDRCGQLDGDPKEISPVFTQFLECVWQLTEQFPRAFEFSEAFLLQIHEHIHS 302
PTP-MTMR6-like cd14532
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases ...
 130-386 0e+00

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: 518.82  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 130 LAEEYKRMGVPNSHWQLSDANRDYKICETYPRELYVPRIASKPIIVGSSKFRSKGRFPVLSYYHQDKE------------ 197
Cdd:cd14532     1 LESEYTRMGVPNDNWTLSDINKDYELCDTYPRELFVPTSASTPVLVGSSKFRSKGRLPVLSYLHKDNQaaicrcsqplsg 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 198 ---------------------------------LNAMANRAAGKGYENEDNYSNIRFQFVGIENIHVMRSSLQKLLEVNG 244
Cdd:cd14532    81 fsarcvedeqllqairkanpnskfmyvvdtrpkINAMANKAAGKGYENEDNYSNIKFQFFGIENIHVMRSSLQKLLEVCE 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 245 TKGLSVNDFYSGLESSGWLRHIKAVMDAAIFLAKAItVENASVLVHCSDGWDRTSQVCSLGSLLLDSYYRTIKGFMVLIE 324
Cdd:cd14532   161 LKNPSMSAFLSGLESSGWLKHIKAVMDTSVFIAKAV-SEGASVLVHCSDGWDRTAQTCSLASLLLDPYYRTIKGFQVLIE 239

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1869284176 325 KDWISFGHKFSERCGQLDGDPKEVSPVFTQFLECVWHLTEQFPQAFEFSEAFLLQIHEHIHS 386
Cdd:cd14532   240 KEWLSFGHKFTDRCGHLQGDAKEVSPVFTQFLDCVWQLMQQFPRAFEFNERFLLTLHDHVYS 301
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
 123-400 5.72e-175

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: 497.77  E-value: 5.72e-175
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 123 QGWQLIDLAEEYKRMGVPN-SHWQLSDANRDYKICETYPRELYVPRIASKPIIVGSSKFRSKGRFPVLSYYH-------- 193
Cdd:pfam06602   3 NGWDLYDPEAEFARQGLPSkDEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHkengavit 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 194 ---------------QDKEL-------------------------NAMANRAAGKGYENEDNYSNIRFQFVGIENIHVMR 233
Cdd:pfam06602  83 rssqplvglngkrsiEDEKLlqaifkssnpysakklyivdarpklNAMANRAKGGGYENEDNYPNCKKIFLGIENIHVMR 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 234 SSLQKLLEVNGTKGLSVNDFYSGLESSGWLRHIKAVMDAAIFLAKAITVENASVLVHCSDGWDRTSQVCSLGSLLLDSYY 313
Cdd:pfam06602 163 DSLNKLVEACNDRSPSMDKWLSRLESSGWLKHIKAILDGACLIAQAVDLEGSSVLVHCSDGWDRTAQLTSLAQLLLDPYY 242

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 314 RTIKGFMVLIEKDWISFGHKFSERCGQLDG--DPKEVSPVFTQFLECVWHLTEQFPQAFEFSEAFLLQIHEHIHSCQFGN 391
Cdd:pfam06602 243 RTIEGFQVLIEKEWLSFGHKFADRCGHLAGftDSKERSPVFLQFLDCVWQLLRQFPCAFEFNERFLIRLLYHLYSCQFGT 322


                  ....*....
gi 1869284176 392 FLGNCQKER 400
Cdd:pfam06602 323 FLCNSEKER 331
PTP-MTMR8 cd14584
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 124-386 3.82e-166

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: 474.75  E-value: 3.82e-166
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 124 GWQLIDLAEEYKRMGVPNSHWQLSDANRDYKICETYPRELYVPRIASKPIIVGSSKFRSKGRFPVLSYYHQDK------- 196
Cdd:cd14584     1 GWKLIDLKVDFQRMGIPNDYWEITDANKNYEICSTYPPELVVPKSASKATVVGSSKFRSRGRFPVLSYLYKENnaaicrc 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 197 --------------------------------------ELNAMANRAAGKGYENEDNYSNIRFQFVGIENIHVMRSSLQK 238
Cdd:cd14584    81 sqplsgfsarcvedeqmlqaiskanpgspfmyvvdtrpKLNAMANRAAGKGYENEDNYSNIRFQFIGIENIHVMRSSLQK 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 239 LLEVNGTKGLSVNDFYSGLESSGWLRHIKAVMDAAIFLAKAITVENASVLVHCSDGWDRTSQVCSLGSLLLDSYYRTIKG 318
Cdd:cd14584   161 LLEVCEMKSPSMSDFLTGLENSGWLRHIKAVMDAGVFLAKAVKEEKASVLVHCSDGWDRTAQVCSLASLLLDPFYRTIKG 240

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1869284176 319 FMVLIEKDWISFGHKFSERCGQLDGDPKEVSPVFTQFLECVWHLTEQFPQAFEFSEAFLLQIHEHIHS 386
Cdd:cd14584   241 LMVLIEKEWISMGHKFSQRCGHLDGDPKEVSPVFTQFLECVWQLMEQFPCAFEFNEHFLLEIHDHVFS 308
PTP-MTMR7 cd14583
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 130-386 1.53e-157

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: 452.49  E-value: 1.53e-157
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 130 LAEEYKRMGVPNSHWQLSDANRDYKICETYPRELYVPRIASKPIIVGSSKFRSKGRFPVLSYYHQDK------------- 196
Cdd:cd14583     1 LKAEYNRMGLPNSLWQVSDVNRDYRVCDTYPTELYVPKSATAPIIVGSSKFRSRGRFPVLSYYCKDNnasicrssqplsg 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 197 --------------------------------ELNAMANRAAGKGYENEDNYSNIRFQFVGIENIHVMRSSLQKLLEVNG 244
Cdd:cd14583    81 fsarcledeqmlqairkanpgsdfmyvvdtrpKLNAMANRAAGKGYENEDNYSNIKFQFIGIENIHVMRNSLQKMLEVCE 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 245 TKGLSVNDFYSGLESSGWLRHIKAVMDAAIFLAKAITVENASVLVHCSDGWDRTSQVCSLGSLLLDSYYRTIKGFMVLIE 324
Cdd:cd14583   161 LRSPSMGDFLWGLENSGWLKHIKAIMDAGIFIAKAVAEEGASVLVHCSDGWDRTAQVCSVASLLLDPYYRTIKGFMVLIE 240

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1869284176 325 KDWISFGHKFSERCGQLDGDPKEVSPVFTQFLECVWHLTEQFPQAFEFSEAFLLQIHEHIHS 386
Cdd:cd14583   241 KDWVSFGHKFNHRYGHLDGDPKEVSPVIDQFIECVWQLMEQFPCAFEFNERFLIHIHHHIYS 302
PTP-MTM-like cd14507
protein tyrosine phosphatase-like domain of myotubularins; Myotubularins are a unique subgroup ...
 184-361 5.62e-94

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: 287.14  E-value: 5.62e-94
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 184 GRFPVLSYYHQDKE----------------------------------------------LNAMANRAAGKGYENEDNYS 217
Cdd:cd14507     1 GRIPVLSWRHPRNGavicrssqplvgltgsrskedekllnairkaspsskklyivdarpkLNAVANRAKGGGYENTEYYP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 218 NIRFQFVGIENIHVMRSSLQKLLEVNGTKGLSVNDFYSGLESSGWLRHIKAVMDAAIFLAKAITVENASVLVHCSDGWDR 297
Cdd:cd14507    81 NCELEFLNIENIHAMRDSLNKLRDACLSPNDEESNWLSALESSGWLEHIRLILKGAVRVADLLEKEGTSVLVHCSDGWDR 160

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1869284176 298 TSQVCSLGSLLLDSYYRTIKGFMVLIEKDWISFGHKFSERCGQLD--GDPKEVSPVFTQFLECVWH 361
Cdd:cd14507   161 TSQLTSLAQLLLDPYYRTIEGFQVLIEKEWLSFGHKFADRCGHGDknSSDEERSPIFLQFLDCVWQ 226
PTP-MTM1-like cd14535
protein tyrosine phosphatase-like domain of myotubularin, and myotubularin related ...
 199-385 2.31e-72

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: 231.95  E-value: 2.31e-72
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 199 NAMANRAAGKGYENEDNYSNIRFQFVGIENIHVMRSSLQKLLEVNGTkglSVND--FYSGLESSGWLRHIKAVMDAAIFL 276
Cdd:cd14535    62 NAVANKAKGGGYESEDAYQNAELVFLDIHNIHVMRESLRKLKDICFP---NIDDshWLSNLESTHWLEHIKLILAGAVRI 138

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 277 AKAITVENASVLVHCSDGWDRTSQVCSLGSLLLDSYYRTIKGFMVLIEKDWISFGHKFSERCGQldGDPK----EVSPVF 352
Cdd:cd14535   139 ADKVESGKTSVVVHCSDGWDRTAQLTSLAMLMLDPYYRTIRGFEVLIEKEWLSFGHKFAQRIGH--GDKNhsdaDRSPVF 216

                         170       180       190
                  ....*....|....*....|....*....|...
gi 1869284176 353 TQFLECVWHLTEQFPQAFEFSEAFLLQIHEHIH 385
Cdd:cd14535   217 LQFIDCVWQMTRQFPNAFEFNEHFLITILDHLY 249
PTP-MTM1 cd14591
protein tyrosine phosphatase-like domain of myotubularin phosphoinositide phosphatase 1; ...
 182-385 2.63e-72

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: 231.84  E-value: 2.63e-72
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 182 SKGRFPVLSYYHQDKELNAMANRAAGKGYENEDNYSNIRFQFVGIENIHVMRSSLQKLLEVNgTKGLSVNDFYSGLESSG 261
Cdd:cd14591    45 ANGQTSKLTIYDARPSVNAVANKATGGGYEGDDAYQNAELVFLDIHNIHVMRESLKKLKDIV-YPNVEESHWLSSLESTH 123

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 262 WLRHIKAVMDAAIFLAKAITVENASVLVHCSDGWDRTSQVCSLGSLLLDSYYRTIKGFMVLIEKDWISFGHKFSERCGQL 341
Cdd:cd14591   124 WLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSYYRTIEGFEVLVQKEWISFGHKFASRIGHG 203

                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1869284176 342 DGDPKEV--SPVFTQFLECVWHLTEQFPQAFEFSEAFLLQIHEHIH 385
Cdd:cd14591   204 DKNHADAdrSPIFLQFIDCVWQMSKQFPTAFEFNEQFLITILDHLY 249
PTP-MTMR2 cd14590
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 178-385 1.08e-70

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: 227.99  E-value: 1.08e-70
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 178 SKFRSKGRFPVLSYYHQDKE----------------------------------------------LNAMANRAAGKGYE 211
Cdd:cd14590     8 ASFRSRGRIPVLSWIHPESQatitrcsqpmvgvsgkrskedekylqaimdsnaqshkififdarpsVNAVANKAKGGGYE 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 212 NEDNYSNIRFQFVGIENIHVMRSSLQKLLEVNgTKGLSVNDFYSGLESSGWLRHIKAVMDAAIFLAKAITVENASVLVHC 291
Cdd:cd14590    88 SEDAYQNAELVFLDIHNIHVMRESLRKLKEIV-YPNIEESHWLSNLESTHWLEHIKLILAGALRIADKVESGKTSVVVHC 166

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 292 SDGWDRTSQVCSLGSLLLDSYYRTIKGFMVLIEKDWISFGHKFSERCGQLDGDPKEV--SPVFTQFLECVWHLTEQFPQA 369
Cdd:cd14590   167 SDGWDRTAQLTSLAMLMLDGYYRTIRGFEVLVEKEWLSFGHRFQLRVGHGDKNHADAdrSPVFLQFIDCVWQMTRQFPTA 246

                         250
                  ....*....|....*.
gi 1869284176 370 FEFSEAFLLQIHEHIH 385
Cdd:cd14590   247 FEFNEYFLITILDHLY 262
PH-GRAM_MTMR6 cd13343
Myotubularian (MTM) related (MTMR) 6 protein Pleckstrin Homology-Glucosyltransferases, ...
 1-101 1.94e-68

Myotubularian (MTM) related (MTMR) 6 protein Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR6 is a member of the myotubularin dual specificity protein phosphatase gene family. MTMR6 binds to phosphoinositide lipids through its PH-GRAM domain. It acts as a negative regulator of KCNN4/KCa3.1 channel activity in CD4+ T-cells possibly by decreasing intracellular levels of phosphatidylinositol-3 phosphatase and negatively regulates proliferation of reactivated CD4+ T-cells MTMR6 interacts with MTMR7, MTMR8 and MTMR9. MTMR6 contains a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an active PTP domain, a SET-interaction domain, and a C-terminal coiled-coil region. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 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: 270151  Cd Length: 101  Bit Score: 216.42  E-value: 1.94e-68
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176   1 MEHIRTTKVEQVKLLDRFSTSNKSLTGTLYLTATHLLFIDSHQKETWILHHHIASVEKLALTTSGCPLVIQCKNFRTVHF 80
Cdd:cd13343     1 MEHIRTTKVEQVKLLDRFSTSNKSLTGTLYLTATHLLFIDNSQQETWILHHHIAPVEKLSLTTSGCPLVIQCKNFRVVHF 80

                          90       100
                  ....*....|....*....|.
gi 1869284176  81 IVPRERDCHDIYNSLLQLSKQ 101
Cdd:cd13343    81 VVPRERDCHDIYNSLLQLSRP 101
PTP-MTM-like_fungal cd17666
protein tyrosine phosphatase-like domain of fungal myotubularins; Myotubularins are a unique ...
 199-360 2.38e-67

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: 218.08  E-value: 2.38e-67
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 199 NAMANRAAGKGYENEDNYSN--IRFQFVGIENIHVMRSSLQKLLEV---NGTKGLSVNDFYSGLESSGWLRHIKAVMDAA 273
Cdd:cd17666    67 NAMAQVALGAGTENMDNYKYktAKKIYLGIDNIHVMRDSLNKVTEAlkdGDDSNPSYPPLINALKKSNWLKYLAIILQGA 146

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 274 IFLAKAITVENASVLVHCSDGWDRTSQVCSLGSLLLDSYYRTIKGFMVLIEKDWISFGHKFSERCGQldgdpKEVSPVFT 353
Cdd:cd17666   147 DLIAKSIHFNHSHVLIHCSDGWDRTSQLSALAQLCLDPYYRTLEGFMVLVEKDWLSFGHRFAERSGH-----KETSPVFH 221


                  ....*..
gi 1869284176 354 QFLECVW 360
Cdd:cd17666   222 QFLDCVY 228
PTP-MTMR1 cd14592
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 195-385 4.69e-64

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: 210.22  E-value: 4.69e-64
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 195 DKELNAMA--NRAAGKGYENEDNYSNIRFQFVGIENIHVMRSSLQKLLEVNgTKGLSVNDFYSGLESSGWLRHIKAVMDA 272
Cdd:cd14592    56 DARQNSVAdtNKTKGGGYESESAYPNAELVFLEIHNIHVMRESLRKLKEIV-YPSIDEARWLSNVDGTHWLEYIRMLLAG 134

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 273 AIFLAKAITVENASVLVHCSDGWDRTSQVCSLGSLLLDSYYRTIKGFMVLIEKDWISFGHKFSERCGQLDGD--PKEVSP 350
Cdd:cd14592   135 AVRIADKIESGKTSVVVHCSDGWDRTAQLTSLAMLMLDSYYRTIKGFEVLIEKEWISFGHRFALRVGHGDDNhaDADRSP 214

                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1869284176 351 VFTQFLECVWHLTEQFPQAFEFSEAFLLQIHEHIH 385
Cdd:cd14592   215 IFLQFIDCVWQMTRQFPSAFEFNELFLITILDHLY 249
PH-GRAM_MTMR6-like cd13210
Myotubularian (MTM) related (MTMR) 7 and 8 proteins Pleckstrin Homology-Glucosyltransferases, ...
 4-100 1.63e-56

Myotubularian (MTM) related (MTMR) 7 and 8 proteins Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR6, MTMR7, and MRMR8 are all member of the myotubularin dual specificity protein phosphatase gene family. They bind to phosphoinositide lipids through its PH-GRAM domain. These proteins also interact with each other as well as MTMR9. 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. 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 lipid-binding FYVE domain has been shown to bind phosphotidylinositol-3-phosphate. 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: 270030  Cd Length: 98  Bit Score: 184.79  E-value: 1.63e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176   4 IRTTKVEQVKLLDRFSTSnKSLTGTLYLTATHLLFID-SHQKETWILHHHIASVEKLALTTSGCPLVIQCKNFRTVHFIV 82
Cdd:cd13210     1 IRTPKVENVRLLDRFSSR-KPAVGTLYLTATHLIFVEpSGKKETWILHSHIASVEKLPLTTAGCPLVIRCKNFQVITFVI 79

                          90
                  ....*....|....*...
gi 1869284176  83 PRERDCHDIYNSLLQLSK 100
Cdd:cd13210    80 PRERDCHDVYTSLLRLSR 97
PTP-MTMR3-like cd14533
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases ...
 200-359 2.23e-55

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: 186.84  E-value: 2.23e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 200 AMANRAAGKGYENEDNYSNIRFQFVGIENIHVMRSSLQKLLEVNGTKGLSVNdFYSGLESSGWLRHIKAVMDAAIFLAKA 279
Cdd:cd14533    67 AVANRAKGGGCECPEYYPNCEVVFMNLANIHAIRKSFHSLRALCSSAPDQPN-WLSNLESTKWLHHLSGLLKAALLVVNA 145

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 280 ITVENASVLVHCSDGWDRTSQVCSLGSLLLDSYYRTIKGFMVLIEKDWISFGHKFSERCGQLDG--DPKEVSPVFTQFLE 357
Cdd:cd14533   146 VDEEGRPVLVHCSDGWDRTPQIVALAELMLDPYYRTIEGFQVLVEREWLDFGHKFADRCGHGVNseDINERCPVFLQWLD 225


                  ..
gi 1869284176 358 CV 359
Cdd:cd14533   226 CV 227
PTP-MTMR4 cd14587
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 144-359 4.45e-54

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: 186.01  E-value: 4.45e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 144 WQLSDANRDYKICETYPRELYVPRIASKPIIVGSSKFRSKGRFPVLSYYHQ----------------------------- 194
Cdd:cd14587     3 WRVSEINSNYKLCSSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLrngaviarcsqpeiswwgwrnaddeylvt 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 195 ----------------------------------DKELN------------------------AMANRAAGKGYENEDNY 216
Cdd:cd14587    83 siakacaldpgtrapggspskgnsdgsdasdtdfDSSLTacsavesgaapqkllildarsytaAVANRAKGGGCECEEYY 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 217 SNIRFQFVGIENIHVMRSSLQKLLEVnGTKGLSVNDFYSGLESSGWLRHIKAVMDAAIFLAKAITVENASVLVHCSDGWD 296
Cdd:cd14587   163 PNCEVMFMGMANIHSIRNSFQYLRAV-CSQMPDPGNWLSALESTKWLQHLSVMLKAAVLVASAVDREGRPVLVHCSDGWD 241

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1869284176 297 RTSQVCSLGSLLLDSYYRTIKGFMVLIEKDWISFGHKFSERCGQLDG--DPKEVSPVFTQFLECV 359
Cdd:cd14587   242 RTPQIVALAKILLDPYYRTIEGFQVLVETDWLDFGHKFGDRCGHQENveDQNEQCPVFLQWLDCV 306
PTP-MTMR9 cd14536
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 184-360 4.70e-49

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: 169.83  E-value: 4.70e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 184 GRFPVLSYYHQD--------------------KE----LNAM-------------------ANRAAGKGYENEDNYSNIR 220
Cdd:cd14536     1 GRFPVLSYYHKKngmvlmrssqpltgpngkrcKEdeklLNAVlgggkrgyiidtrsknvaqQARAKGGGFEPEAHYPQWR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 221 FQFVGIENIHVMRSSLQKLLEVNGTKGLSVNDFYSGLESSGWLRHIKAVMDAAIFLAKAITVENASVLVHCSDGWDRTSQ 300
Cdd:cd14536    81 RIHKPIERYNVLQESLIKLVEACNDQGHSMDKWLSKLESSNWLSHVKEILTTACLVAQCIDREGASVLVHGSEGMDSTLQ 160

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1869284176 301 VCSLGSLLLDSYYRTIKGFMVLIEKDWISFGHKFSERCGQL---DGDPKEVSPVFTQFLECVW 360
Cdd:cd14536   161 VTSLAQIILDPDCRTIRGFEALIEREWLQAGHPFQSRCAKSaysNSKQKFESPVFLLFLDCVW 223
PTP-MTMR3 cd14586
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 141-359 1.40e-48

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: 171.36  E-value: 1.40e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 141 NSHWQLSDANRDYKICETYPRELYVPRIASKPIIVGSSKFRSKGRFPVLSYYHQ-----------------------DKE 197
Cdd:cd14586     5 QNAWRISNINEKYKLCGSYPQELIVPAWITDKELESVASFRSWKRIPAVVYRHQsngaviarcgqpevswwgwrnadDEH 84

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 198 L--------------------------------------------------------------------NAMANRAAGKG 209
Cdd:cd14586    85 LvqsvakacasdssscksvlmtgncsrdfpnggdlsdvefdssmsnasgveslaiqpqkllildarsyaAAVANRAKGGG 164

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 210 YENEDNYSNIRFQFVGIENIHVMRSSLQKLlEVNGTKGLSVNDFYSGLESSGWLRHIKAVMDAAIFLAKAITVENASVLV 289
Cdd:cd14586   165 CECPEYYPNCEVVFMGMANIHSIRKSFQSL-RLLCTQMPDPANWLSALESTKWLQHLSMLLKSALLVVHAVDRDQRPVLV 243

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1869284176 290 HCSDGWDRTSQVCSLGSLLLDSYYRTIKGFMVLIEKDWISFGHKFSERCGQLDG--DPKEVSPVFTQFLECV 359
Cdd:cd14586   244 HCSDGWDRTPQIVALSKLLLDPYYRTIEGFQVLVETEWLDFGHKFADRCGHGENsdDLNERCPVFLQWLDCV 315
PH-GRAM_MTMR8 cd13345
Myotubularian (MTM) related 8 protein (MTMR8) Pleckstrin Homology-Glucosyltransferases, ...
 1-100 2.71e-45

Myotubularian (MTM) related 8 protein (MTMR8) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR8 is a member of the myotubularin dual specificity protein phosphatase gene family. MTMR8 binds to phosphoinositide lipids through its PH-GRAM domain. MTMR8 can self associate and interacts with MTMR6, MTMR7 and MTMR9. MTMR8 contains a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an active PTP domain, a SET-interaction domain, and a C-terminal coiled-coil region. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 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: 270153  Cd Length: 103  Bit Score: 155.12  E-value: 2.71e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176   1 MEHIRTTKVEQVKLLDRFsTSNKSLTGTLYLTATHLLFIDSH---QKETWILHHHIASVEKLALTTSGCPLVIQCKNFRT 77
Cdd:cd13345     1 MEHITTPKVENVKLLDRY-TNKKPANGTLYLTATHLIYVEASgaaRKETWILHHHIATVEKLPLTSLGCPLLIRCKNFRV 79

                          90       100
                  ....*....|....*....|...
gi 1869284176  78 VHFIVPRERDCHDIYNSLLQLSK 100
Cdd:cd13345    80 AHFVLDSERDCHEVYISLLKLSQ 102
PTP-MTMR5-like cd14534
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 144-365 5.10e-42

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: 152.14  E-value: 5.10e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 144 WQLSDANRDYKICETYPRELYVP---------RIA-----------------SKPIIVGSSKFRSKGRF----------- 186
Cdd:cd14534     1 FRISTANRDYSICRSYPALVVVPqsvsdeslrKVArcyrqgrfpvvtwrhprTKALLLRSGGFHGKGVMgmlksantsts 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 187 -------PVLSYYHQDKELNAMA-----NRAAGKGYENEdnySNIRFQFVGIE--NIHVMRSSLQKLLE------VNGTK 246
Cdd:cd14534    81 sptvsssETSSSLEQEKYLSALVlyvlgEKSQMKGVKAE---SDPKCEFIPVEypEVRQVKASFKKLLRacvpssAPTEP 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 247 GLSvndFYSGLESSGWLRHIKAVMDAAIFLAKAITVENASVLVHCSDGWDRTSQVCSLGSLLLDSYYRTIKGFMVLIEKD 326
Cdd:cd14534   158 EQS---FLKAVEDSEWLQQLQCLMQLSGAVVDLLDVQGSSVLLCLEDGWDVTTQVSSLSQLLLDPYYRTLEGFRVLVEKE 234

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 1869284176 327 WISFGHKFSERCGQLDGDPKE-VSPVFTQFLECVWHLTEQ 365
Cdd:cd14534   235 WLAFGHRFSHRSNLTAASQSSgFAPVFLQFLDAVHQIHRQ 274
PH-GRAM_MTMR7 cd13344
Myotubularian (MTM) related 7 protein (MTMR7) Pleckstrin Homology-Glucosyltransferases, ...
 1-100 6.72e-41

Myotubularian (MTM) related 7 protein (MTMR7) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR7 is a member of the myotubularin dual specificity protein phosphatase gene family. MTMR6 binds to phosphoinositide lipids through its PH-GRAM domain and can hydrolyze phosphatidylinositol(3)-phosphate and phosphatidylinositol(3,5)-biphosphate. MTMR7 interacts with MTMR6, MTMR8 and MTMR9. MTMR7 contains a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an active PTP domain, a SET-interaction domain, and a C-terminal coiled-coil region. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 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: 270152  Cd Length: 103  Bit Score: 143.52  E-value: 6.72e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176   1 MEHIRTTKVEQVKLLDRFStSNKSLTGTLYLTATHLLFIDSH---QKETWILHHHIASVEKLALTTSGCPLVIQCKNFRT 77
Cdd:cd13344     1 MEHIRMPKVENVRLVDRIS-SKKAALGTLYLTATHVIFVENSsdtRKETWILHSQISSIEKQATTATGCPLLIRCKNFQV 79

                          90       100
                  ....*....|....*....|...
gi 1869284176  78 VHFIVPRERDCHDIYNSLLQLSK 100
Cdd:cd13344    80 IQLIIPQERDCHDVYISLIRLAR 102
PTP-MTMR5 cd14588
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 144-359 5.47e-28

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: 113.91  E-value: 5.47e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 144 WQLSDANRDYKICETYPRELYVPRIASKPIIVGSSKFRSKGRFPVL---------------------------------- 189
Cdd:cd14588     1 FRISTVNRMYAVCRSYPGLLIVPQSIQDNTIQRISRCYRQNRFPVVcwrnsrtkavllrsgglhgkgvvglfksqnapaa 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 190 -------SYYHQDKELNAMAN-----------------RAAGKGYENEDNYSNIR------FQFVGIE--NIHVMRSSLQ 237
Cdd:cd14588    81 gqsqtdsTSLEQEKYLQAVINsmpryadasgrntlsgfRAALYIIGDKSQLKGVKqdplqqWEVVPIEvfDVRQVKASFK 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 238 KLLEVNGTKGLSVN---DFYSGLESSGWLRHIKAVMDAAIFLAKAITvENASVLVHCSDGWDRTSQVCSLGSLLLDSYYR 314
Cdd:cd14588   161 KLMKACVPSCPSTDpsqTYLRTLEESEWLSQLHKLLQVSVLVVELLD-SGSSVLVSLEDGWDITTQVVSLVQLLSDPYYR 239

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*.
gi 1869284176 315 TIKGFMVLIEKDWISFGHKFSERCGQ-LDGDPKEVSPVFTQFLECV 359
Cdd:cd14588   240 TIEGFRLLVEKEWLSFGHRFSHRGAQtLASQSSGFTPVFLQFLDCV 285
PTP-MTMR10-like cd14537
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 251-360 1.12e-27

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: 110.12  E-value: 1.12e-27
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 251 NDFYSGLESSGWLRHIKAVMDAAIFLAKAITVENASVLVHCSDGWDRTSQVCSLGSLLLDSYYRTIKGFMVLIEKDWISF 330
Cdd:cd14537    88 SKWYSLLENTKWLHYVSACLKKASEAAEALESRGRSVVLQESDGRDLSCVVSSLVQLLLDPHFRTITGFQSLIQKEWVAL 167

                          90       100       110
                  ....*....|....*....|....*....|..
gi 1869284176 331 GHKFSERCG--QLDGDPKEVSPVFTQFLECVW 360
Cdd:cd14537   168 GHPFCDRLGhvKPNKTESEESPVFLLFLDCVW 199
PTP-MTMR13 cd14589
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 222-365 8.55e-26

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: 107.70  E-value: 8.55e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 222 QFVGIE--NIHVMRSSLQKLLEVNGTKGLSVND---FYSGLESSGWLRHIKAVMDAAIFLAKAITvENASVLVHCSDGWD 296
Cdd:cd14589   149 EFVPVEfhDIRQVKASFKKLMRACVPSTIPTDSevtFLKALGESEWFLQLHRIMQLAVVISELLE-SGSSVMVCLEDGWD 227

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 297 RTSQVCSLGSLLLDSYYRTIKGFMVLIEKDWISFGHKFSERCG-QLDGDPKEVSPVFTQFLECVWHLTEQ 365
Cdd:cd14589   228 ITTQVVSLVQLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQRSNlTPNSQGSGFAPIFLQFLDCVHQIHNQ 297
PTP-MTMR12 cd14594
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 254-362 7.51e-23

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: 96.45  E-value: 7.51e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 254 YSGLESSGWLRHIKAVMDAAIFLAKAITVENASVLVHCSDGWDRTSQVCSLGSLLLDSYYRTIKGFMVLIEKDWISFGHK 333
Cdd:cd14594    95 FSSLESSNWLEIIRQCLKKAVEVVECLEKQNTNVLLTEEEATDLCCVISSLVQIMMDPYCRTKSGFQSLIQKEWVMGGHC 174

                          90       100
                  ....*....|....*....|....*....
gi 1869284176 334 FSERCGQLDGDPKEVSPVFTQFLECVWHL 362
Cdd:cd14594   175 FLDRCNHLRQNDKEEVPVFLLFLDCVWQL 203
PTP-MTMR11 cd14595
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 249-362 5.29e-21

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: 91.05  E-value: 5.29e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 249 SVNDFYSGLESSGWLRHIKAVMDAAIFLAKAITVENASVLVHCSDGWDRTSQVCSLGSLLLDSYYRTIKGFMVLIEKDWI 328
Cdd:cd14595    82 SDEKWLSNLEGTRWLDHVRACLRKASEVSCLLAERHRSVILQESEDRDLNCLLSSLVQLLSDPHARTISGFQSLVQKEWV 161

                          90       100       110
                  ....*....|....*....|....*....|....
gi 1869284176 329 SFGHKFSERCGQLDGDPKEVSPVFTQFLECVWHL 362
Cdd:cd14595   162 VAGHPFLQRLNLTRESDKEESPVFLLFLDCVWQL 195
PTP-MTMR10 cd14593
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 228-360 1.56e-19

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: 86.87  E-value: 1.56e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176 228 NIHVMRSSLQKLlevngtKGLSVND--------FYSGLESSGWLRHIKAVMDAAIFLAKAITVENASVLVHCSDGWDRTS 299
Cdd:cd14593    60 NIQEIQAAFVKL------KQLCVNEpfeeteekWLSSLESTRWLEYVRAFLKHSAELVYMLESKHVSVILQEEEGRDLSC 133

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1869284176 300 QVCSLGSLLLDSYYRTIKGFMVLIEKDWISFGHKFSERCGQLDGDPKEVSPVFTQFLECVW 360
Cdd:cd14593   134 VVASLVQVMLDPYFRTITGFQSLIQKEWVMAGYRFLDRCNHLKKSSKKESPLFLLFLDCVW 194
PH-GRAM cd10570
Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins ...
 4-95 1.71e-15

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: 72.03  E-value: 1.71e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176   4 IRTTKVEQVKLLDrfsTSNKSLTGTLYLTATHLLFIDS---HQKETWILHHHIASVEKLA-LTTSGCPLVIQCKNFRTVH 79
Cdd:cd10570     1 IEKLGVRFCCALR---PRKLPLEGTLYLSTYRLIFSSKadgDETKLVIPLVDITDVEKIAgASFLPSGLIITCKDFRTIK 77

                          90
                  ....*....|....*..
gi 1869284176  80 FIVPRE-RDCHDIYNSL 95
Cdd:cd10570    78 FSFDSEdEAVKVIARVL 94
PH-GRAM_MTMR9 cd13211
Myotubularian (MTM) related 9 protein (MTMR9) Pleckstrin Homology-Glucosyltransferases, ...
 1-95 3.98e-14

Myotubularian (MTM) related 9 protein (MTMR9) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR9 is a catalytically inactive phosphatase that plays a role as an adapter for the phosphatase myotubularin to regulate myotubularintracellular location. It contains a Gly residue instead of a conserved Cys residue in the dsPTPase catalytic loop which renders it catalytically inactive as a phosphatase. MTMR9 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 region. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 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: 275398  Cd Length: 99  Bit Score: 68.46  E-value: 3.98e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176   1 MEHIRTTKVEQVKLLDRFstsNKSLTGTLYLTATHLLFIDS--HQKETWILHHHIASVEK-LALTTSGCPLVIQCKNFRT 77
Cdd:cd13211     4 AELIKTPKVDNVVLHRPP---RPAVEGTLCITGHHLILSSRqdNAEELWLLHSNIDSVEKkFVGKSSGGTLTLKCKDFRI 80

                          90
                  ....*....|....*...
gi 1869284176  78 VHFIVPRERDCHDIYNSL 95
Cdd:cd13211    81 IQLDIPDMEECLNIASSI 98
PTPc_motif smart00404
Protein tyrosine phosphatase, catalytic domain motif;
263-317 1.59e-05

Protein tyrosine phosphatase, catalytic domain motif;


Pssm-ID: 214649 [Multi-domain]  Cd Length: 105  Bit Score: 43.89  E-value: 1.59e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1869284176  263 LRHIKAVMDAaiflaKAITVENASVLVHCSDGWDRTSQVCSLGSLLLDSYYRTIK 317
Cdd:smart00404  23 LELLRAVKKN-----LNQSESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEAGE 72
PTPc_DSPc smart00012
Protein tyrosine phosphatase, catalytic domain, undefined specificity; Protein tyrosine ...
 263-317 1.59e-05

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


Pssm-ID: 214469 [Multi-domain]  Cd Length: 105  Bit Score: 43.89  E-value: 1.59e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1869284176  263 LRHIKAVMDAaiflaKAITVENASVLVHCSDGWDRTSQVCSLGSLLLDSYYRTIK 317
Cdd:smart00012  23 LELLRAVKKN-----LNQSESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEAGE 72
PH-GRAM_MTM-like cd13223
Myotubularian 1 and related proteins Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase; ...
 8-95 5.68e-03

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: 36.45  E-value: 5.68e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1869284176   8 KVEQVKLLDRFstsNKSLTGTLYLTATHLLFIDSHQKETWILHHH---IASVEKLALTTSG----CPLVIQCKNFRTVHF 80
Cdd:cd13223     2 KEKDVTYLCPF---RGPVRGTLYITNYRLYFKSRDREPNFVLDVPlgvISRVEKVGGATSRgensYGLEIHCKDMRNLRF 78

                          90
                  ....*....|....*.
gi 1869284176  81 I-VPRERDCHDIYNSL 95
Cdd:cd13223    79 AhKQENHSRRKLYETL 94
 
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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