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Conserved domains on  [gi|4557896|ref|NP_000243|]
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myotubularin isoform 1 [Homo sapiens]

Protein Classification

PH-GRAM_MTM1 and PTP-MTM1 domain-containing protein( domain architecture ID 10193444)

PH-GRAM_MTM1 and PTP-MTM1 domain-containing protein

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
 162-489 0e+00

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


:

Pssm-ID: 461958 [Multi-domain]  Cd Length: 332  Bit Score: 589.83  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896    162 DGWTVYNPVEEYRRQGLPNH-HWRITFINKCYELCDTYPALLVVPYRASDDDLRRVATFRSRNRIPVLSWIHPENKTVIV 240
Cdd:pfam06602   3 NGWDLYDPEAEFARQGLPSKdEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHKENGAVIT 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896    241 RCSQPLVGMSGKRNKDDEKYLDVIRETNKQIS--KLTIYDARPSVNAVANKATGGGYESDDAYHNAELFFLDIHNIHVMR 318
Cdd:pfam06602  83 RSSQPLVGLNGKRSIEDEKLLQAIFKSSNPYSakKLYIVDARPKLNAMANRAKGGGYENEDNYPNCKKIFLGIENIHVMR 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896    319 ESLKKVKDIVYP-NVEESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFY 397
Cdd:pfam06602 163 DSLNKLVEACNDrSPSMDKWLSRLESSGWLKHIKAILDGACLIAQAVDLEGSSVLVHCSDGWDRTAQLTSLAQLLLDPYY 242

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896    398 RSIEGFEILVQKEWISFGHKFASRIGHGDKNHTDADRSPIFLQFIDCVWQMSKQFPTAFEFNEQFLIIILDHLYSCRFGT 477
Cdd:pfam06602 243 RTIEGFQVLIEKEWLSFGHKFADRCGHLAGFTDSKERSPVFLQFLDCVWQLLRQFPCAFEFNERFLIRLLYHLYSCQFGT 322

                         330
                  ....*....|..
gi 4557896    478 FLFNCEsaRERQ 489
Cdd:pfam06602 323 FLCNSE--KERV 332
PH-GRAM_MTM1 cd13355
Myotubularian 1 protein (MTM1) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase ...
 44-143 1.31e-69

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


:

Pssm-ID: 270162  Cd Length: 100  Bit Score: 220.11  E-value: 1.31e-69
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896   44 ITDKEVIYICPFNGPIKGRVYITNYRLYLRSLETDSSLILDVPLGVISRIEKMGGATSRGENSYGLDITCKDMRNLRFAL 123
Cdd:cd13355   1 VTDKDVIYICPFNGPVKGRVYITNYRLYFKSTESEPPVTLDVPLGVISRIEKMGGASSRGENSYGLDITCKDMRNLRFAL 80

                        90       100
                ....*....|....*....|
gi 4557896  124 KQEGHSRRDMFEILTRYAFP 143
Cdd:cd13355  81 KQEGHSRRDIFEILTKYAFP 100
 
Name Accession Description Interval E-value
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
 162-489 0e+00

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


Pssm-ID: 461958 [Multi-domain]  Cd Length: 332  Bit Score: 589.83  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896    162 DGWTVYNPVEEYRRQGLPNH-HWRITFINKCYELCDTYPALLVVPYRASDDDLRRVATFRSRNRIPVLSWIHPENKTVIV 240
Cdd:pfam06602   3 NGWDLYDPEAEFARQGLPSKdEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHKENGAVIT 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896    241 RCSQPLVGMSGKRNKDDEKYLDVIRETNKQIS--KLTIYDARPSVNAVANKATGGGYESDDAYHNAELFFLDIHNIHVMR 318
Cdd:pfam06602  83 RSSQPLVGLNGKRSIEDEKLLQAIFKSSNPYSakKLYIVDARPKLNAMANRAKGGGYENEDNYPNCKKIFLGIENIHVMR 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896    319 ESLKKVKDIVYP-NVEESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFY 397
Cdd:pfam06602 163 DSLNKLVEACNDrSPSMDKWLSRLESSGWLKHIKAILDGACLIAQAVDLEGSSVLVHCSDGWDRTAQLTSLAQLLLDPYY 242

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896    398 RSIEGFEILVQKEWISFGHKFASRIGHGDKNHTDADRSPIFLQFIDCVWQMSKQFPTAFEFNEQFLIIILDHLYSCRFGT 477
Cdd:pfam06602 243 RTIEGFQVLIEKEWLSFGHKFADRCGHLAGFTDSKERSPVFLQFLDCVWQLLRQFPCAFEFNERFLIRLLYHLYSCQFGT 322

                         330
                  ....*....|..
gi 4557896    478 FLFNCEsaRERQ 489
Cdd:pfam06602 323 FLCNSE--KERV 332
PTP-MTM1 cd14591
protein tyrosine phosphatase-like domain of myotubularin phosphoinositide phosphatase 1; ...
 223-471 0e+00

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: 566.19  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  223 NRIPVLSWIHPENKTVIVRCSQPLVGMSGKRNKDDEKYLDVIRETNKQISKLTIYDARPSVNAVANKATGGGYESDDAYH 302
Cdd:cd14591   1 NRIPVLSWIHPENQAVIMRCSQPLVGMSGKRNKDDEKYLDIIREANGQTSKLTIYDARPSVNAVANKATGGGYEGDDAYQ 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  303 NAELFFLDIHNIHVMRESLKKVKDIVYPNVEESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWDRT 382
Cdd:cd14591  81 NAELVFLDIHNIHVMRESLKKLKDIVYPNVEESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWDRT 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  383 AQLTSLAMLMLDSFYRSIEGFEILVQKEWISFGHKFASRIGHGDKNHTDADRSPIFLQFIDCVWQMSKQFPTAFEFNEQF 462
Cdd:cd14591 161 AQLTSLAMLMLDSYYRTIEGFEVLVQKEWISFGHKFASRIGHGDKNHADADRSPIFLQFIDCVWQMSKQFPTAFEFNEQF 240


                ....*....
gi 4557896  463 LIIILDHLY 471
Cdd:cd14591 241 LITILDHLY 249
PH-GRAM_MTM1 cd13355
Myotubularian 1 protein (MTM1) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase ...
 44-143 1.31e-69

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


Pssm-ID: 270162  Cd Length: 100  Bit Score: 220.11  E-value: 1.31e-69
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896   44 ITDKEVIYICPFNGPIKGRVYITNYRLYLRSLETDSSLILDVPLGVISRIEKMGGATSRGENSYGLDITCKDMRNLRFAL 123
Cdd:cd13355   1 VTDKDVIYICPFNGPVKGRVYITNYRLYFKSTESEPPVTLDVPLGVISRIEKMGGASSRGENSYGLDITCKDMRNLRFAL 80

                        90       100
                ....*....|....*....|
gi 4557896  124 KQEGHSRRDMFEILTRYAFP 143
Cdd:cd13355  81 KQEGHSRRDIFEILTKYAFP 100
GRAM pfam02893
GRAM domain; The GRAM domain is found in in glucosyltransferases, myotubularins and other ...
 35-143 4.51e-21

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


Pssm-ID: 397160  Cd Length: 112  Bit Score: 88.58  E-value: 4.51e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896     35 VPRLPGETLITDkeviYICPFN---GPIKGRVYITNYRLYLRSLETDSSLILDVPLGVISRIEKMGGATSRGENSYGLDI 111
Cdd:pfam02893   7 FKLPPEERLIAS----YSCYLNrdgGPVQGRLYLTNYRLCFRSLPKGWSTKVVIPLVDIEEIEKLKGGANLFPNGIQVET 82

                          90       100       110
                  ....*....|....*....|....*....|..
gi 4557896    112 TCKDmrNLRFALKQEGHSRRDMFEILTRYAFP 143
Cdd:pfam02893  83 GSND--KFSFAGFVTRDEAIEFILALLKNAHP 112
GRAM smart00568
domain in glucosyltransferases, myotubularins and other putative membrane-associated proteins;
38-97 6.97e-13

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


Pssm-ID: 214725 [Multi-domain]  Cd Length: 60  Bit Score: 63.38  E-value: 6.97e-13
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4557896      38 LPGETLITDkeviYICPFN--GPIKGRVYITNYRLYLRSLETDSSLILDVPLGVISRIEKMG 97
Cdd:smart00568   3 PEEEKLIAD----YSCYLSrtGPVQGRLYISNYRLCFRSNLPGKLTKVVIPLADITRIEKST 60
PTPc_motif smart00404
Protein tyrosine phosphatase, catalytic domain motif;
365-471 1.93e-10

Protein tyrosine phosphatase, catalytic domain motif;


Pssm-ID: 214649 [Multi-domain]  Cd Length: 105  Bit Score: 58.14  E-value: 1.93e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896     365 SSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFYRSiegfeilvqkewisfghkfasrighgdknhtdadrspIFLQFIDC 444
Cdd:smart00404  36 SESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEA-------------------------------------GEVDIFDT 78

                           90       100
                   ....*....|....*....|....*..
gi 4557896     445 VWQMSKQFPTAFEFNEQFLIIILDHLY 471
Cdd:smart00404  79 VKELRSQRPGMVQTEEQYLFLYRALLE 105
 
Name Accession Description Interval E-value
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
 162-489 0e+00

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


Pssm-ID: 461958 [Multi-domain]  Cd Length: 332  Bit Score: 589.83  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896    162 DGWTVYNPVEEYRRQGLPNH-HWRITFINKCYELCDTYPALLVVPYRASDDDLRRVATFRSRNRIPVLSWIHPENKTVIV 240
Cdd:pfam06602   3 NGWDLYDPEAEFARQGLPSKdEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHKENGAVIT 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896    241 RCSQPLVGMSGKRNKDDEKYLDVIRETNKQIS--KLTIYDARPSVNAVANKATGGGYESDDAYHNAELFFLDIHNIHVMR 318
Cdd:pfam06602  83 RSSQPLVGLNGKRSIEDEKLLQAIFKSSNPYSakKLYIVDARPKLNAMANRAKGGGYENEDNYPNCKKIFLGIENIHVMR 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896    319 ESLKKVKDIVYP-NVEESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFY 397
Cdd:pfam06602 163 DSLNKLVEACNDrSPSMDKWLSRLESSGWLKHIKAILDGACLIAQAVDLEGSSVLVHCSDGWDRTAQLTSLAQLLLDPYY 242

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896    398 RSIEGFEILVQKEWISFGHKFASRIGHGDKNHTDADRSPIFLQFIDCVWQMSKQFPTAFEFNEQFLIIILDHLYSCRFGT 477
Cdd:pfam06602 243 RTIEGFQVLIEKEWLSFGHKFADRCGHLAGFTDSKERSPVFLQFLDCVWQLLRQFPCAFEFNERFLIRLLYHLYSCQFGT 322

                         330
                  ....*....|..
gi 4557896    478 FLFNCEsaRERQ 489
Cdd:pfam06602 323 FLCNSE--KERV 332
PTP-MTM1 cd14591
protein tyrosine phosphatase-like domain of myotubularin phosphoinositide phosphatase 1; ...
 223-471 0e+00

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: 566.19  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  223 NRIPVLSWIHPENKTVIVRCSQPLVGMSGKRNKDDEKYLDVIRETNKQISKLTIYDARPSVNAVANKATGGGYESDDAYH 302
Cdd:cd14591   1 NRIPVLSWIHPENQAVIMRCSQPLVGMSGKRNKDDEKYLDIIREANGQTSKLTIYDARPSVNAVANKATGGGYEGDDAYQ 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  303 NAELFFLDIHNIHVMRESLKKVKDIVYPNVEESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWDRT 382
Cdd:cd14591  81 NAELVFLDIHNIHVMRESLKKLKDIVYPNVEESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWDRT 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  383 AQLTSLAMLMLDSFYRSIEGFEILVQKEWISFGHKFASRIGHGDKNHTDADRSPIFLQFIDCVWQMSKQFPTAFEFNEQF 462
Cdd:cd14591 161 AQLTSLAMLMLDSYYRTIEGFEVLVQKEWISFGHKFASRIGHGDKNHADADRSPIFLQFIDCVWQMSKQFPTAFEFNEQF 240


                ....*....
gi 4557896  463 LIIILDHLY 471
Cdd:cd14591 241 LITILDHLY 249
PTP-MTM1-like cd14535
protein tyrosine phosphatase-like domain of myotubularin, and myotubularin related ...
 223-471 0e+00

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: 525.09  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  223 NRIPVLSWIHPENKTVIVRCSQPLVGMSGKRNKDDEKYLDVIRETNKQISKLTIYDARPSVNAVANKATGGGYESDDAYH 302
Cdd:cd14535   1 NRIPVLSWIHPESQATITRCSQPLVGVSGKRSKDDEKYLQLIMDANAQSHKLFIMDARPSVNAVANKAKGGGYESEDAYQ 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  303 NAELFFLDIHNIHVMRESLKKVKDIVYPNVEESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWDRT 382
Cdd:cd14535  81 NAELVFLDIHNIHVMRESLRKLKDICFPNIDDSHWLSNLESTHWLEHIKLILAGAVRIADKVESGKTSVVVHCSDGWDRT 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  383 AQLTSLAMLMLDSFYRSIEGFEILVQKEWISFGHKFASRIGHGDKNHTDADRSPIFLQFIDCVWQMSKQFPTAFEFNEQF 462
Cdd:cd14535 161 AQLTSLAMLMLDPYYRTIRGFEVLIEKEWLSFGHKFAQRIGHGDKNHSDADRSPVFLQFIDCVWQMTRQFPNAFEFNEHF 240


                ....*....
gi 4557896  463 LIIILDHLY 471
Cdd:cd14535 241 LITILDHLY 249
PTP-MTMR2 cd14590
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 210-471 2.89e-180

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: 509.58  E-value: 2.89e-180
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  210 DDDLRRVATFRSRNRIPVLSWIHPENKTVIVRCSQPLVGMSGKRNKDDEKYLDVIRETNKQISKLTIYDARPSVNAVANK 289
Cdd:cd14590   1 DEELKRVASFRSRGRIPVLSWIHPESQATITRCSQPMVGVSGKRSKEDEKYLQAIMDSNAQSHKIFIFDARPSVNAVANK 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  290 ATGGGYESDDAYHNAELFFLDIHNIHVMRESLKKVKDIVYPNVEESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGKS 369
Cdd:cd14590  81 AKGGGYESEDAYQNAELVFLDIHNIHVMRESLRKLKEIVYPNIEESHWLSNLESTHWLEHIKLILAGALRIADKVESGKT 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  370 SVLVHCSDGWDRTAQLTSLAMLMLDSFYRSIEGFEILVQKEWISFGHKFASRIGHGDKNHTDADRSPIFLQFIDCVWQMS 449
Cdd:cd14590 161 SVVVHCSDGWDRTAQLTSLAMLMLDGYYRTIRGFEVLVEKEWLSFGHRFQLRVGHGDKNHADADRSPVFLQFIDCVWQMT 240

                       250       260
                ....*....|....*....|..
gi 4557896  450 KQFPTAFEFNEQFLIIILDHLY 471
Cdd:cd14590 241 RQFPTAFEFNEYFLITILDHLY 262
PTP-MTMR1 cd14592
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 224-471 3.64e-151

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: 435.18  E-value: 3.64e-151
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  224 RIPVLSWIHPENKTVIVRCSQPLVGMSGKRNKDDEKYLDVIRETNKQISKLTIYDARPSVNAVANKATGGGYESDDAYHN 303
Cdd:cd14592   2 RVPVLSWIHPESQATITRCSQPLVGPNDKRCKEDEKYLQTIMDANAQSHKLIIFDARQNSVADTNKTKGGGYESESAYPN 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  304 AELFFLDIHNIHVMRESLKKVKDIVYPNVEESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWDRTA 383
Cdd:cd14592  82 AELVFLEIHNIHVMRESLRKLKEIVYPSIDEARWLSNVDGTHWLEYIRMLLAGAVRIADKIESGKTSVVVHCSDGWDRTA 161

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  384 QLTSLAMLMLDSFYRSIEGFEILVQKEWISFGHKFASRIGHGDKNHTDADRSPIFLQFIDCVWQMSKQFPTAFEFNEQFL 463
Cdd:cd14592 162 QLTSLAMLMLDSYYRTIKGFEVLIEKEWISFGHRFALRVGHGDDNHADADRSPIFLQFIDCVWQMTRQFPSAFEFNELFL 241


                ....*...
gi 4557896  464 IIILDHLY 471
Cdd:cd14592 242 ITILDHLY 249
PTP-MTM-like cd14507
protein tyrosine phosphatase-like domain of myotubularins; Myotubularins are a unique subgroup ...
 223-447 1.88e-139

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: 404.24  E-value: 1.88e-139
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  223 NRIPVLSWIHPENKTVIVRCSQPLVGMSGKRNKDDEKYLDVIRETNKQISKLTIYDARPSVNAVANKATGGGYESDDAYH 302
Cdd:cd14507   1 GRIPVLSWRHPRNGAVICRSSQPLVGLTGSRSKEDEKLLNAIRKASPSSKKLYIVDARPKLNAVANRAKGGGYENTEYYP 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  303 NAELFFLDIHNIHVMRESLKKVKDIVY-PNVEESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWDR 381
Cdd:cd14507  81 NCELEFLNIENIHAMRDSLNKLRDACLsPNDEESNWLSALESSGWLEHIRLILKGAVRVADLLEKEGTSVLVHCSDGWDR 160

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4557896  382 TAQLTSLAMLMLDSFYRSIEGFEILVQKEWISFGHKFASRIGHGDKNHTDADRSPIFLQFIDCVWQ 447
Cdd:cd14507 161 TSQLTSLAQLLLDPYYRTIEGFQVLIEKEWLSFGHKFADRCGHGDKNSSDEERSPIFLQFLDCVWQ 226
PTP-MTMR6-like cd14532
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases ...
 169-472 4.64e-138

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: 403.65  E-value: 4.64e-138
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  169 PVEEYRRQGLPNHHWRITFINKCYELCDTYPALLVVPYRASDDDLRRVATFRSRNRIPVLSWIHPENKTVIVRCSQPLVG 248
Cdd:cd14532   1 LESEYTRMGVPNDNWTLSDINKDYELCDTYPRELFVPTSASTPVLVGSSKFRSKGRLPVLSYLHKDNQAAICRCSQPLSG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  249 MSGkRNKDDEKYLDVIRETNKQISKLTIYDARPSVNAVANKATGGGYESDDAYHNAELFFLDIHNIHVMRESLKKVKDIV 328
Cdd:cd14532  81 FSA-RCVEDEQLLQAIRKANPNSKFMYVVDTRPKINAMANKAAGKGYENEDNYSNIKFQFFGIENIHVMRSSLQKLLEVC 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  329 -YPNVEESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGkSSVLVHCSDGWDRTAQLTSLAMLMLDSFYRSIEGFEILV 407
Cdd:cd14532 160 eLKNPSMSAFLSGLESSGWLKHIKAVMDTSVFIAKAVSEG-ASVLVHCSDGWDRTAQTCSLASLLLDPYYRTIKGFQVLI 238

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4557896  408 QKEWISFGHKFASRIGHGDknhTDA-DRSPIFLQFIDCVWQMSKQFPTAFEFNEQFLIIILDHLYS 472
Cdd:cd14532 239 EKEWLSFGHKFTDRCGHLQ---GDAkEVSPVFTQFLDCVWQLMQQFPRAFEFNERFLLTLHDHVYS 301
PTP-MTMR8 cd14584
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 163-472 3.56e-118

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: 353.02  E-value: 3.56e-118
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  163 GWTVYNPVEEYRRQGLPNHHWRITFINKCYELCDTYPALLVVPYRASDDDLRRVATFRSRNRIPVLSWIHPENKTVIVRC 242
Cdd:cd14584   1 GWKLIDLKVDFQRMGIPNDYWEITDANKNYEICSTYPPELVVPKSASKATVVGSSKFRSRGRFPVLSYLYKENNAAICRC 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  243 SQPLVGMSGkRNKDDEKYLDVIRETNKQISKLTIYDARPSVNAVANKATGGGYESDDAYHNAELFFLDIHNIHVMRESLK 322
Cdd:cd14584  81 SQPLSGFSA-RCVEDEQMLQAISKANPGSPFMYVVDTRPKLNAMANRAAGKGYENEDNYSNIRFQFIGIENIHVMRSSLQ 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  323 K---VKDIVYPNVeeSHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFYRS 399
Cdd:cd14584 160 KlleVCEMKSPSM--SDFLTGLENSGWLRHIKAVMDAGVFLAKAVKEEKASVLVHCSDGWDRTAQVCSLASLLLDPFYRT 237

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4557896  400 IEGFEILVQKEWISFGHKFASRIGHGDKNHTDAdrSPIFLQFIDCVWQMSKQFPTAFEFNEQFLIIILDHLYS 472
Cdd:cd14584 238 IKGLMVLIEKEWISMGHKFSQRCGHLDGDPKEV--SPVFTQFLECVWQLMEQFPCAFEFNEHFLLEIHDHVFS 308
PTP-MTMR6 cd14585
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 171-472 2.63e-109

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: 330.35  E-value: 2.63e-109
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  171 EEYRRQGLPNHHWRITFINKCYELCDTYPALLVVPYRASDDDLRRVATFRSRNRIPVLSWIHPENKTVIVRCSQPLVGMS 250
Cdd:cd14585   3 EEYKRMGVPNDYWQLSDVNRDYKICDTYPRDLYVPITASKPIIVGSSKFRSKGRFPVLSYYHQEKKAAICRCSQPLSGFS 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  251 GkRNKDDEKYLDVIRETNKQISKLTIYDARPSVNAVANKATGGGYESDDAYHNAELFFLDIHNIHVMRESLKKVKDIV-Y 329
Cdd:cd14585  83 A-RCLEDEHMLQAISKANPNNRYMYVMDTRPKLNAMANRAAGKGYENEDNYSNIRFQFVGIENIHVMRSSLQKLLEVCgT 161

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  330 PNVEESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFYRSIEGFEILVQK 409
Cdd:cd14585 162 KALSVNDFLSGLESSGWLRHIKAVLDAAVFLAKAVAVEGASVLVHCSDGWDRTAQVCSLGSLLLDPYYRTIKGFMVLIEK 241

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4557896  410 EWISFGHKFASRIGHGDKNHTDAdrSPIFLQFIDCVWQMSKQFPTAFEFNEQFLIIILDHLYS 472
Cdd:cd14585 242 DWISFGHKFSDRCGQLDGDPKEI--SPVFTQFLECVWQLTEQFPRAFEFSEAFLLQIHEHIHS 302
PTP-MTMR7 cd14583
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 171-472 9.81e-107

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: 323.45  E-value: 9.81e-107
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  171 EEYRRQGLPNHHWRITFINKCYELCDTYPALLVVPYRASDDDLRRVATFRSRNRIPVLSWIHPENKTVIVRCSQPLVGMS 250
Cdd:cd14583   3 AEYNRMGLPNSLWQVSDVNRDYRVCDTYPTELYVPKSATAPIIVGSSKFRSRGRFPVLSYYCKDNNASICRSSQPLSGFS 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  251 GkRNKDDEKYLDVIRETNKQISKLTIYDARPSVNAVANKATGGGYESDDAYHNAELFFLDIHNIHVMRESLKK---VKDI 327
Cdd:cd14583  83 A-RCLEDEQMLQAIRKANPGSDFMYVVDTRPKLNAMANRAAGKGYENEDNYSNIKFQFIGIENIHVMRNSLQKmleVCEL 161

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  328 VYPNVEESHWlsSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFYRSIEGFEILV 407
Cdd:cd14583 162 RSPSMGDFLW--GLENSGWLKHIKAIMDAGIFIAKAVAEEGASVLVHCSDGWDRTAQVCSVASLLLDPYYRTIKGFMVLI 239

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 4557896  408 QKEWISFGHKFASRIGHGDKNHTDAdrSPIFLQFIDCVWQMSKQFPTAFEFNEQFLIIILDHLYS 472
Cdd:cd14583 240 EKDWVSFGHKFNHRYGHLDGDPKEV--SPVIDQFIECVWQLMEQFPCAFEFNERFLIHIHHHIYS 302
PTP-MTMR4 cd14587
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 183-447 1.32e-84

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: 266.90  E-value: 1.32e-84
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  183 WRITFINKCYELCDTYPALLVVPYRASDDDLRRVATFRSRNRIPVLSWIHPENKTVIVRCSQPLVGMSGKRNKDDEKYLD 262
Cdd:cd14587   3 WRVSEINSNYKLCSSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLRNGAVIARCSQPEISWWGWRNADDEYLVT 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  263 VI----------RETNKQIS-------------------------------KLTIYDARPSVNAVANKATGGGYESDDAY 301
Cdd:cd14587  83 SIakacaldpgtRAPGGSPSkgnsdgsdasdtdfdssltacsavesgaapqKLLILDARSYTAAVANRAKGGGCECEEYY 162

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  302 HNAELFFLDIHNIHVMRESLKKVKDIVYPNVEESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWDR 381
Cdd:cd14587 163 PNCEVMFMGMANIHSIRNSFQYLRAVCSQMPDPGNWLSALESTKWLQHLSVMLKAAVLVASAVDREGRPVLVHCSDGWDR 242

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4557896  382 TAQLTSLAMLMLDSFYRSIEGFEILVQKEWISFGHKFASRIGHGDKNHTDADRSPIFLQFIDCVWQ 447
Cdd:cd14587 243 TPQIVALAKILLDPYYRTIEGFQVLVETDWLDFGHKFGDRCGHQENVEDQNEQCPVFLQWLDCVHQ 308
PTP-MTMR3 cd14586
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 180-447 9.25e-84

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: 264.96  E-value: 9.25e-84
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  180 NHHWRITFINKCYELCDTYPALLVVPYRASDDDLRRVATFRSRNRIPVLSWIHPENKTVIVRCSQPLVGMSGKRNKDDEK 259
Cdd:cd14586   5 QNAWRISNINEKYKLCGSYPQELIVPAWITDKELESVASFRSWKRIPAVVYRHQSNGAVIARCGQPEVSWWGWRNADDEH 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  260 YLDVIRE-------------------------------------TNK--------QISKLTIYDARPSVNAVANKATGGG 294
Cdd:cd14586  85 LVQSVAKacasdssscksvlmtgncsrdfpnggdlsdvefdssmSNAsgveslaiQPQKLLILDARSYAAAVANRAKGGG 164

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  295 YESDDAYHNAELFFLDIHNIHVMRESLKKVKDIVYPNVEESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVH 374
Cdd:cd14586 165 CECPEYYPNCEVVFMGMANIHSIRKSFQSLRLLCTQMPDPANWLSALESTKWLQHLSMLLKSALLVVHAVDRDQRPVLVH 244

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 4557896  375 CSDGWDRTAQLTSLAMLMLDSFYRSIEGFEILVQKEWISFGHKFASRIGHGDKNHTDADRSPIFLQFIDCVWQ 447
Cdd:cd14586 245 CSDGWDRTPQIVALSKLLLDPYYRTIEGFQVLVETEWLDFGHKFADRCGHGENSDDLNERCPVFLQWLDCVHQ 317
PTP-MTMR3-like cd14533
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases ...
 223-447 6.23e-82

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: 256.95  E-value: 6.23e-82
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  223 NRIPVLSWIHPENKTVIVRCSQPLVGMSGKRNKDDEKYLDVIRET---NKQISKLTIYDARPSVNAVANKATGGGYESDD 299
Cdd:cd14533   2 KRIPSVVWRHQRNGAVIARCSQPEVGWLGWRNAEDENLLQAIAEAcasNASPKKLLIVDARSYAAAVANRAKGGGCECPE 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  300 AYHNAELFFLDIHNIHVMRESLKKVKDIVYPNVEESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGW 379
Cdd:cd14533  82 YYPNCEVVFMNLANIHAIRKSFHSLRALCSSAPDQPNWLSNLESTKWLHHLSGLLKAALLVVNAVDEEGRPVLVHCSDGW 161

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 4557896  380 DRTAQLTSLAMLMLDSFYRSIEGFEILVQKEWISFGHKFASRIGHGDKNHTDADRSPIFLQFIDCVWQ 447
Cdd:cd14533 162 DRTPQIVALAELMLDPYYRTIEGFQVLVEREWLDFGHKFADRCGHGVNSEDINERCPVFLQWLDCVHQ 229
PTP-MTM-like_fungal cd17666
protein tyrosine phosphatase-like domain of fungal myotubularins; Myotubularins are a unique ...
 223-447 7.26e-79

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: 248.90  E-value: 7.26e-79
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  223 NRIPVLSWIHPENKTVIVRCSQPLVGMSGKRNKDDEKYLDVI-----RETNKQISKLTIYDARPSVNAVANKATGGGYES 297
Cdd:cd17666   1 QRIPVLTYLHKANGCSITRSSQPLVGLKQNRSIQDEKLVSEIfntsiNEIYISPQKNLIVDARPTTNAMAQVALGAGTEN 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  298 DDAYHN--AELFFLDIHNIHVMRESLKKVKDIV----YPNVEESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSV 371
Cdd:cd17666  81 MDNYKYktAKKIYLGIDNIHVMRDSLNKVTEALkdgdDSNPSYPPLINALKKSNWLKYLAIILQGADLIAKSIHFNHSHV 160

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4557896  372 LVHCSDGWDRTAQLTSLAMLMLDSFYRSIEGFEILVQKEWISFGHKFASRIGHGDKnhtdadrSPIFLQFIDCVWQ 447
Cdd:cd17666 161 LIHCSDGWDRTSQLSALAQLCLDPYYRTLEGFMVLVEKDWLSFGHRFAERSGHKET-------SPVFHQFLDCVYQ 229
PH-GRAM_MTM1 cd13355
Myotubularian 1 protein (MTM1) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase ...
 44-143 1.31e-69

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


Pssm-ID: 270162  Cd Length: 100  Bit Score: 220.11  E-value: 1.31e-69
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896   44 ITDKEVIYICPFNGPIKGRVYITNYRLYLRSLETDSSLILDVPLGVISRIEKMGGATSRGENSYGLDITCKDMRNLRFAL 123
Cdd:cd13355   1 VTDKDVIYICPFNGPVKGRVYITNYRLYFKSTESEPPVTLDVPLGVISRIEKMGGASSRGENSYGLDITCKDMRNLRFAL 80

                        90       100
                ....*....|....*....|
gi 4557896  124 KQEGHSRRDMFEILTRYAFP 143
Cdd:cd13355  81 KQEGHSRRDIFEILTKYAFP 100
PTP-MTMR9 cd14536
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 224-447 1.96e-61

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: 202.95  E-value: 1.96e-61
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  224 RIPVLSWIHPENKTVIVRCSQPLVGMSGKRNKDDEKYLDVIRETNKqisKLTIYDARPSVNAVANKATGGGYESDDAYHN 303
Cdd:cd14536   2 RFPVLSYYHKKNGMVLMRSSQPLTGPNGKRCKEDEKLLNAVLGGGK---RGYIIDTRSKNVAQQARAKGGGFEPEAHYPQ 78

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  304 AELFFLDIHNIHVMRESLKK-VKDIVYPNVEESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWDRT 382
Cdd:cd14536  79 WRRIHKPIERYNVLQESLIKlVEACNDQGHSMDKWLSKLESSNWLSHVKEILTTACLVAQCIDREGASVLVHGSEGMDST 158

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 4557896  383 AQLTSLAMLMLDSFYRSIEGFEILVQKEWISFGHKFASRIGHGDKNHT-DADRSPIFLQFIDCVWQ 447
Cdd:cd14536 159 LQVTSLAQIILDPDCRTIRGFEALIEREWLQAGHPFQSRCAKSAYSNSkQKFESPVFLLFLDCVWQ 224
PH-GRAM_MTM-like cd13223
Myotubularian 1 and related proteins Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase; ...
 44-143 6.54e-59

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: 191.68  E-value: 6.54e-59
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896   44 ITDKEVIYICPFNGPIKGRVYITNYRLYLRSLETDSSLILDVPLGVISRIEKMGGATSRGENSYGLDITCKDMRNLRFAL 123
Cdd:cd13223   1 LKEKDVTYLCPFRGPVRGTLYITNYRLYFKSRDREPNFVLDVPLGVISRVEKVGGATSRGENSYGLEIHCKDMRNLRFAH 80

                        90       100
                ....*....|....*....|
gi 4557896  124 KQEGHSRRDMFEILTRYAFP 143
Cdd:cd13223  81 KQENHSRRKLYETLQKYAFP 100
PTP-MTMR5-like cd14534
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 183-451 6.61e-58

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: 195.66  E-value: 6.61e-58
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  183 WRITFINKCYELCDTYPALLVVPYRASDDDLRRVATFRSRNRIPVLSWIHPENKTVIVRCSQP----LVGMSGKRNKDDE 258
Cdd:cd14534   1 FRISTANRDYSICRSYPALVVVPQSVSDESLRKVARCYRQGRFPVVTWRHPRTKALLLRSGGFhgkgVMGMLKSANTSTS 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  259 KYLDVIRETN------KQISKLTIYdarpsvnAVANKATGGGYESDdAYHNAELFFLDIHNIHVMRESLKKVKDIVYP-- 330
Cdd:cd14534  81 SPTVSSSETSssleqeKYLSALVLY-------VLGEKSQMKGVKAE-SDPKCEFIPVEYPEVRQVKASFKKLLRACVPss 152

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  331 -NVE-ESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFYRSIEGFEILVQ 408
Cdd:cd14534 153 aPTEpEQSFLKAVEDSEWLQQLQCLMQLSGAVVDLLDVQGSSVLLCLEDGWDVTTQVSSLSQLLLDPYYRTLEGFRVLVE 232

                       250       260       270       280
                ....*....|....*....|....*....|....*....|...
gi 4557896  409 KEWISFGHKFASRiGHGDKNHTDADRSPIFLQFIDCVWQMSKQ 451
Cdd:cd14534 233 KEWLAFGHRFSHR-SNLTAASQSSGFAPVFLQFLDAVHQIHRQ 274
PTP-MTMR13 cd14589
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 183-451 3.51e-51

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: 178.19  E-value: 3.51e-51
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  183 WRITFINKCYELCDTYPALLVVPYRASDDDLRRVATFRSRNRIPVLSWIHPENKTVIVRC----SQPLVGMSGKRNK--- 255
Cdd:cd14589   1 FRITAVNRMYSLCRSYPGLLVVPQSVQDSSLQKVARCYRHNRLPVVCWKNSKTKAVLLRSggfhGKGVVGLFKSQNPhsa 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  256 -----------DDEKYLDVIRETNKQISKLT---------IYDARPSVNAVANKATGGGYESDDAYhNAELFFLDIHNIH 315
Cdd:cd14589  81 apassessssiEQEKYLQALLNAISVHQKMNgnstllqsqLLKRQAALYIFGEKSQLRGFKLDFAL-NCEFVPVEFHDIR 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  316 VMRESLKKVKDIVYPNV----EESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGkSSVLVHCSDGWDRTAQLTSLAML 391
Cdd:cd14589 160 QVKASFKKLMRACVPSTiptdSEVTFLKALGESEWFLQLHRIMQLAVVISELLESG-SSVMVCLEDGWDITTQVVSLVQL 238

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  392 MLDSFYRSIEGFEILVQKEWISFGHKFASRiGHGDKNHTDADRSPIFLQFIDCVWQMSKQ 451
Cdd:cd14589 239 LSDPFYRTLEGFQMLVEKEWLSFGHKFSQR-SNLTPNSQGSGFAPIFLQFLDCVHQIHNQ 297
PH-GRAM_MTMR2_insect-like cd13357
Myotubularian related 2 protein (MTMR2) Pleckstrin Homology-Glucosyltransferases, Rab-like ...
 47-143 3.73e-50

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


Pssm-ID: 270164  Cd Length: 100  Bit Score: 168.45  E-value: 3.73e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896   47 KEVIYICPFNGPIKGRVYITNYRLYLRSLETDSSLILDVPLGVISRIEKMGGATSRGENSYGLDITCKDMRNLRFALKQE 126
Cdd:cd13357   4 KDVTYLCPFRGPVRGTLTITNYKLYFKSLDREPPFTVEVPLGVIYRVEKVGGATSRGENSYGLEIFCKDMRNLRFAHKQE 83

                        90
                ....*....|....*..
gi 4557896  127 GHSRRDMFEILTRYAFP 143
Cdd:cd13357  84 NHSRRLVFEKLQAYAFP 100
PTP-MTMR5 cd14588
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 183-451 4.12e-47

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: 167.07  E-value: 4.12e-47
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  183 WRITFINKCYELCDTYPALLVVPYRASDDDLRRVATFRSRNRIPVLSWIHPENKTVIVRC----SQPLVGMSGKRNK--- 255
Cdd:cd14588   1 FRISTVNRMYAVCRSYPGLLIVPQSIQDNTIQRISRCYRQNRFPVVCWRNSRTKAVLLRSgglhGKGVVGLFKSQNApaa 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  256 ----------DDEKYLDVIRETNKQISKL----TIYDARPSVNAVANKATGGGYESDdAYHNAELFFLDIHNIHVMRESL 321
Cdd:cd14588  81 gqsqtdstslEQEKYLQAVINSMPRYADAsgrnTLSGFRAALYIIGDKSQLKGVKQD-PLQQWEVVPIEVFDVRQVKASF 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  322 KKVKDIVYPNVEES----HWLSSLESTHWLEHIKLVLTGAIQVADKVSSGkSSVLVHCSDGWDRTAQLTSLAMLMLDSFY 397
Cdd:cd14588 160 KKLMKACVPSCPSTdpsqTYLRTLEESEWLSQLHKLLQVSVLVVELLDSG-SSVLVSLEDGWDITTQVVSLVQLLSDPYY 238

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 4557896  398 RSIEGFEILVQKEWISFGHKFASRighgdKNHTDADRS----PIFLQFIDCVWQMSKQ 451
Cdd:cd14588 239 RTIEGFRLLVEKEWLSFGHRFSHR-----GAQTLASQSsgftPVFLQFLDCVHQIHLQ 291
PH-GRAM_MTMR2_mammal-like cd13356
Myotubularian related 2 protein (MTMR2) Pleckstrin Homology-Glucosyltransferases, Rab-like ...
 33-145 2.34e-45

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


Pssm-ID: 270163  Cd Length: 115  Bit Score: 156.39  E-value: 2.34e-45
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896   33 EAVPRLPGETlITD--KEVIYICPFNGPIKGRVYITNYRLYLRSLETDSSLILDVPLGVISRIEKMGGATSRGENSYGLD 110
Cdd:cd13356   2 EEPPLLPGEN-IKDmaKDVTYICPFTGAVRGTLTVTNYRLYFKSMERDPPFVLDASLGVINRVEKIGGASSRGENSYGLE 80

                        90       100       110
                ....*....|....*....|....*....|....*
gi 4557896  111 ITCKDMRNLRFALKQEGHSRRDMFEILTRYAFPLA 145
Cdd:cd13356  81 TVCKDIRNLRFAHKPEGRTRRSIFENLMKYAFPVS 115
PTP-MTMR10-like cd14537
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 223-447 1.42e-38

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: 140.94  E-value: 1.42e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  223 NRIPVLSWIHPeNKTVIVRCS--QPLVGMSgkrnKDDEKYLDVIRETNKQISKLTIYDarPSVNAVANKATGGGYESDda 300
Cdd:cd14537   1 GRPPVWCWSHP-NGAALVRMAelLPTITDR----TQENKMLEAIRKSHPNLKKPKVID--LDKLLPSLQDVQAAYLKL-- 71

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  301 yhnAELFFLDihnihvmreSLKKVKDIvypnveESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWD 380
Cdd:cd14537  72 ---RELCTPD---------SSEQFWVQ------DSKWYSLLENTKWLHYVSACLKKASEAAEALESRGRSVVLQESDGRD 133

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 4557896  381 RTAQLTSLAMLMLDSFYRSIEGFEILVQKEWISFGHKFASRIGHGDKNHTDADRSPIFLQFIDCVWQ 447
Cdd:cd14537 134 LSCVVSSLVQLLLDPHFRTITGFQSLIQKEWVALGHPFCDRLGHVKPNKTESEESPVFLLFLDCVWQ 200
PH-GRAM_MTMR1 cd13358
Myotubularian related 1 protein (MTMR1) Pleckstrin Homology-Glucosyltransferases, Rab-like ...
 47-143 4.18e-38

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


Pssm-ID: 270165  Cd Length: 100  Bit Score: 136.19  E-value: 4.18e-38
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896   47 KEVIYICPFNGPIKGRVYITNYRLYLRSLETDSSLILDVPLGVISRIEKMgGATSRGENSYGLDITCKDMRNLRFALKQE 126
Cdd:cd13358   5 KDVMYICPFMGAVSGTLTVTDFKMYFKNVERDPPFILDVPLGVISRVEKI-GVQSHGDNSCGIEIVCKDMRNLRLAYKQE 83

                        90
                ....*....|....*..
gi 4557896  127 GHSRRDMFEILTRYAFP 143
Cdd:cd13358  84 EQSKLEIFENLNKHAFP 100
PTP-MTMR11 cd14595
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 332-448 1.22e-29

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: 115.70  E-value: 1.22e-29
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  332 VEESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFYRSIEGFEILVQKEW 411
Cdd:cd14595  81 VSDEKWLSNLEGTRWLDHVRACLRKASEVSCLLAERHRSVILQESEDRDLNCLLSSLVQLLSDPHARTISGFQSLVQKEW 160

                        90       100       110
                ....*....|....*....|....*....|....*...
gi 4557896  412 ISFGHKFASRIG-HGDknhTDADRSPIFLQFIDCVWQM 448
Cdd:cd14595 161 VVAGHPFLQRLNlTRE---SDKEESPVFLLFLDCVWQL 195
PTP-MTMR10 cd14593
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 224-447 5.91e-27

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: 108.06  E-value: 5.91e-27
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  224 RIPVLSWIHPeNKTVIVRCS--QPLVgmsgKRNKDDEKYLDVIRETNKQISKLtiydarpsvnavankatgggYESDday 301
Cdd:cd14593   2 RIPLWCWNHP-NGSALVRMAniKDLL----QQRKIDQRICNAITRSHPLRSDV--------------------YKSD--- 53

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  302 hnaelffLD--IHNIHVMRESLKKVKDI-VYPNVEESH--WLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCS 376
Cdd:cd14593  54 -------LDktLPNIQEIQAAFVKLKQLcVNEPFEETEekWLSSLESTRWLEYVRAFLKHSAELVYMLESKHVSVILQEE 126

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 4557896  377 DGWDRTAQLTSLAMLMLDSFYRSIEGFEILVQKEWISFGHKFASRIGHGDKnhTDADRSPIFLQFIDCVWQ 447
Cdd:cd14593 127 EGRDLSCVVASLVQVMLDPYFRTITGFQSLIQKEWVMAGYRFLDRCNHLKK--SSKKESPLFLLFLDCVWQ 195
PTP-MTMR12 cd14594
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 337-448 1.52e-26

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: 107.23  E-value: 1.52e-26
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  337 WLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFYRSIEGFEILVQKEWISFGH 416
Cdd:cd14594  94 WFSSLESSNWLEIIRQCLKKAVEVVECLEKQNTNVLLTEEEATDLCCVISSLVQIMMDPYCRTKSGFQSLIQKEWVMGGH 173

                        90       100       110
                ....*....|....*....|....*....|..
gi 4557896  417 KFASRIGHGDKNhtDADRSPIFLQFIDCVWQM 448
Cdd:cd14594 174 CFLDRCNHLRQN--DKEEVPVFLLFLDCVWQL 203
GRAM pfam02893
GRAM domain; The GRAM domain is found in in glucosyltransferases, myotubularins and other ...
 35-143 4.51e-21

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


Pssm-ID: 397160  Cd Length: 112  Bit Score: 88.58  E-value: 4.51e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896     35 VPRLPGETLITDkeviYICPFN---GPIKGRVYITNYRLYLRSLETDSSLILDVPLGVISRIEKMGGATSRGENSYGLDI 111
Cdd:pfam02893   7 FKLPPEERLIAS----YSCYLNrdgGPVQGRLYLTNYRLCFRSLPKGWSTKVVIPLVDIEEIEKLKGGANLFPNGIQVET 82

                          90       100       110
                  ....*....|....*....|....*....|..
gi 4557896    112 TCKDmrNLRFALKQEGHSRRDMFEILTRYAFP 143
Cdd:pfam02893  83 GSND--KFSFAGFVTRDEAIEFILALLKNAHP 112
PH-GRAM cd10570
Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins ...
 47-137 5.83e-13

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: 64.71  E-value: 5.83e-13
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896   47 KEVIYICPFNGPIKGRVYITNYRLYLRSLETDSSLILDVPLGVISRIEKMGGATSrgeNSYGLDITCKDMRNLRFALKQE 126
Cdd:cd10570   7 RFCCALRPRKLPLEGTLYLSTYRLIFSSKADGDETKLVIPLVDITDVEKIAGASF---LPSGLIITCKDFRTIKFSFDSE 83

                        90
                ....*....|.
gi 4557896  127 GHSRRDMFEIL 137
Cdd:cd10570  84 DEAVKVIARVL 94
GRAM smart00568
domain in glucosyltransferases, myotubularins and other putative membrane-associated proteins;
38-97 6.97e-13

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


Pssm-ID: 214725 [Multi-domain]  Cd Length: 60  Bit Score: 63.38  E-value: 6.97e-13
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 4557896      38 LPGETLITDkeviYICPFN--GPIKGRVYITNYRLYLRSLETDSSLILDVPLGVISRIEKMG 97
Cdd:smart00568   3 PEEEKLIAD----YSCYLSrtGPVQGRLYISNYRLCFRSNLPGKLTKVVIPLADITRIEKST 60
PTPc_motif smart00404
Protein tyrosine phosphatase, catalytic domain motif;
365-471 1.93e-10

Protein tyrosine phosphatase, catalytic domain motif;


Pssm-ID: 214649 [Multi-domain]  Cd Length: 105  Bit Score: 58.14  E-value: 1.93e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896     365 SSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFYRSiegfeilvqkewisfghkfasrighgdknhtdadrspIFLQFIDC 444
Cdd:smart00404  36 SESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEA-------------------------------------GEVDIFDT 78

                           90       100
                   ....*....|....*....|....*..
gi 4557896     445 VWQMSKQFPTAFEFNEQFLIIILDHLY 471
Cdd:smart00404  79 VKELRSQRPGMVQTEEQYLFLYRALLE 105
PTPc_DSPc smart00012
Protein tyrosine phosphatase, catalytic domain, undefined specificity; Protein tyrosine ...
 365-471 1.93e-10

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: 58.14  E-value: 1.93e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896     365 SSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFYRSiegfeilvqkewisfghkfasrighgdknhtdadrspIFLQFIDC 444
Cdd:smart00012  36 SESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEA-------------------------------------GEVDIFDT 78

                           90       100
                   ....*....|....*....|....*..
gi 4557896     445 VWQMSKQFPTAFEFNEQFLIIILDHLY 471
Cdd:smart00012  79 VKELRSQRPGMVQTEEQYLFLYRALLE 105
PTP_DSP_cys cd14494
cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This ...
 354-422 4.65e-05

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.


Pssm-ID: 350344 [Multi-domain]  Cd Length: 113  Bit Score: 43.11  E-value: 4.65e-05
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 4557896  354 LTGAIQVADKVSSGKSSVLVHCSDGWDRTAQLTSLAMLMldsfyRSIEGFEILVQKEWISFGHKFASRI 422
Cdd:cd14494  42 VDRFLEVLDQAEKPGEPVLVHCKAGVGRTGTLVACYLVL-----LGGMSAEEAVRIVRLIRPGGIPQTI 105
PH-like cd00900
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
 49-131 1.46e-03

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


Pssm-ID: 275390  Cd Length: 89  Bit Score: 38.15  E-value: 1.46e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896   49 VIYICPFNGPIKGRVYITNYRLYLRSlETDSSLILDVPLGVISRIEKmggaTSRGENSYGLDITCKDMRN-LRFALKQEG 127
Cdd:cd00900   6 VRVYREPTKRVEGTLYITSDRLILRD-KNDGGLELSIPISDIVNVNV----SPQGPSSRYLVLVLKDRGEfVGFSFPKEE 80


                ....
gi 4557896  128 HSRR 131
Cdd:cd00900  81 DAIE 84
DSP_DUSP4 cd14640
dual specificity phosphatase domain of dual specificity protein phosphatase 4; Dual ...
 300-412 6.70e-03

dual specificity phosphatase domain of dual specificity protein phosphatase 4; Dual specificity protein phosphatase 4 (DUSP4), also called mitogen-activated protein kinase (MAPK) phosphatase 2 (MKP-2), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). Like other MKPs, it deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. It belongs to the class I subfamily and is a mitogen- and stress-inducible nuclear MKP. DUSP4 regulates either ERK or c-JUN N-terminal kinase (JNK), depending on the cell type. It dephosphorylates nuclear JNK and induces apoptosis in diffuse large B cell lymphoma (DLBCL) cells. It acts as a negative regulator of macrophage M1 activation and inhibits inflammation during macrophage-adipocyte interaction. It has been linked to different aspects of cancer: it may have a role in the development of ovarian cancers, oesophagogastric rib metastasis, and pancreatic tumours; it may also be a candidate tumor suppressor gene, with its deletion implicated in breast cancer, prostate cancer, and gliomas. DUSP4/MKP-2 contains an N-terminal Cdc25/rhodanese-like domain, which is responsible for MAPK-binding, and a C-terminal catalytic dual specificity phosphatase domain.


Pssm-ID: 350488 [Multi-domain]  Cd Length: 141  Bit Score: 37.32  E-value: 6.70e-03
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 4557896  300 AYHNAELFFLDIHNIHVMresLKKVKDIvyPNVEESHWLSS---LESTHwLEHIKLVLTGAIQVADKVSSGKSSVLVHCS 376
Cdd:cd14640  13 AYHAARRDMLDALGITAL---LNVSSDC--PNHFEGHYQYKcipVEDNH-KADISSWFMEAIEYIDSVKDCNGRVLVHCQ 86

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 4557896  377 DGWDRTAQLTsLAMLMLDSFYRSIEGFEILVQKEWI 412
Cdd:cd14640  87 AGISRSATIC-LAYLMMKKRVRLEEAFEFVKQRRSI 121
 
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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