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Conserved domains on  [gi|255958300|ref|NP_064310|]
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myotubularin isoform 1 [Mus musculus]

Protein Classification

myotubularin family protein( domain architecture ID 10352270)

myotubularin family protein similar to myotubularin, a protein tyrosine phosphatase that dephosphorylates phosphatidylinositol 3-monophosphate (PI3P) and phosphatidylinositol 3,5-bisphosphate (PI(3,5)P2)

CATH:  3.90.190.10
EC:  3.1.3.64
Gene Ontology:  GO:0004438|GO:0046856|GO:0035091|GO:0004721|GO:0006470
PubMed:  9736772|16289848|12925573|27514797
SCOP:  4001084

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: 587.52  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300  162 DGWTVYNPVEEYRRQGLPNH-HWRISFINKCYELCETYPALLVVPYRTSDDDLRRIATFRSRNRLPVLSWIHPENKMVIM 240
Cdd:pfam06602   3 NGWDLYDPEAEFARQGLPSKdEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHKENGAVIT 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300  241 RCSQPLVGMSGKRNKDDEKYLDVIRETNKQTS--KLMIYDARPSVNAVANKATGGGYESDDAYQNSELSFLDIHNIHVMR 318
Cdd:pfam06602  83 RSSQPLVGLNGKRSIEDEKLLQAIFKSSNPYSakKLYIVDARPKLNAMANRAKGGGYENEDNYPNCKKIFLGIENIHVMR 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300  319 ESLKKVKDIVYP-NIEESHWLSSLESTHWLEHIKLVLTGAIQVADQVSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFY 397
Cdd:pfam06602 163 DSLNKLVEACNDrSPSMDKWLSRLESSGWLKHIKAILDGACLIAQAVDLEGSSVLVHCSDGWDRTAQLTSLAQLLLDPYY 242

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300  398 RTIEGFEILVQKEWISFGHKFASRIGHGDKNHADADRSPIFLQFIDCVWQMSKQFPTAFEFNEGFLITVLDHLYSCRFGT 477
Cdd:pfam06602 243 RTIEGFQVLIEKEWLSFGHKFADRCGHLAGFTDSKERSPVFLQFLDCVWQLLRQFPCAFEFNERFLIRLLYHLYSCQFGT 322

                         330
                  ....*....|..
gi 255958300  478 FLFNCDsaRERQ 489
Cdd:pfam06602 323 FLCNSE--KERV 332
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
 44-143 2.07e-67

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


The actual alignment was detected with superfamily member cd13355:

Pssm-ID: 473070  Cd Length: 100  Bit Score: 214.33  E-value: 2.07e-67
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300  44 ITEKEVIYICPFNGPIKGRVYITNYRLYLRSLETDSALILDVPLGVISRIEKMGGATSRGENSYGLDITCKDLRNLRFAL 123
Cdd:cd13355    1 VTDKDVIYICPFNGPVKGRVYITNYRLYFKSTESEPPVTLDVPLGVISRIEKMGGASSRGENSYGLDITCKDMRNLRFAL 80

                         90       100
                 ....*....|....*....|
gi 255958300 124 KQEGHSRRDMFEILVKHAFP 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: 587.52  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300  162 DGWTVYNPVEEYRRQGLPNH-HWRISFINKCYELCETYPALLVVPYRTSDDDLRRIATFRSRNRLPVLSWIHPENKMVIM 240
Cdd:pfam06602   3 NGWDLYDPEAEFARQGLPSKdEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHKENGAVIT 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300  241 RCSQPLVGMSGKRNKDDEKYLDVIRETNKQTS--KLMIYDARPSVNAVANKATGGGYESDDAYQNSELSFLDIHNIHVMR 318
Cdd:pfam06602  83 RSSQPLVGLNGKRSIEDEKLLQAIFKSSNPYSakKLYIVDARPKLNAMANRAKGGGYENEDNYPNCKKIFLGIENIHVMR 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300  319 ESLKKVKDIVYP-NIEESHWLSSLESTHWLEHIKLVLTGAIQVADQVSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFY 397
Cdd:pfam06602 163 DSLNKLVEACNDrSPSMDKWLSRLESSGWLKHIKAILDGACLIAQAVDLEGSSVLVHCSDGWDRTAQLTSLAQLLLDPYY 242

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300  398 RTIEGFEILVQKEWISFGHKFASRIGHGDKNHADADRSPIFLQFIDCVWQMSKQFPTAFEFNEGFLITVLDHLYSCRFGT 477
Cdd:pfam06602 243 RTIEGFQVLIEKEWLSFGHKFADRCGHLAGFTDSKERSPVFLQFLDCVWQLLRQFPCAFEFNERFLIRLLYHLYSCQFGT 322

                         330
                  ....*....|..
gi 255958300  478 FLFNCDsaRERQ 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: 556.56  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 223 NRLPVLSWIHPENKMVIMRCSQPLVGMSGKRNKDDEKYLDVIRETNKQTSKLMIYDARPSVNAVANKATGGGYESDDAYQ 302
Cdd:cd14591    1 NRIPVLSWIHPENQAVIMRCSQPLVGMSGKRNKDDEKYLDIIREANGQTSKLTIYDARPSVNAVANKATGGGYEGDDAYQ 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 303 NSELSFLDIHNIHVMRESLKKVKDIVYPNIEESHWLSSLESTHWLEHIKLVLTGAIQVADQVSSGKSSVLVHCSDGWDRT 382
Cdd:cd14591   81 NAELVFLDIHNIHVMRESLKKLKDIVYPNVEESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWDRT 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 383 AQLTSLAMLMLDSFYRTIEGFEILVQKEWISFGHKFASRIGHGDKNHADADRSPIFLQFIDCVWQMSKQFPTAFEFNEGF 462
Cdd:cd14591  161 AQLTSLAMLMLDSYYRTIEGFEVLVQKEWISFGHKFASRIGHGDKNHADADRSPIFLQFIDCVWQMSKQFPTAFEFNEQF 240


                 ....*....
gi 255958300 463 LITVLDHLY 471
Cdd:cd14591  241 LITILDHLY 249
PH-GRAM_MTM1 cd13355
Myotubularian 1 protein (MTM1) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase ...
 44-143 2.07e-67

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: 214.33  E-value: 2.07e-67
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300  44 ITEKEVIYICPFNGPIKGRVYITNYRLYLRSLETDSALILDVPLGVISRIEKMGGATSRGENSYGLDITCKDLRNLRFAL 123
Cdd:cd13355    1 VTDKDVIYICPFNGPVKGRVYITNYRLYFKSTESEPPVTLDVPLGVISRIEKMGGASSRGENSYGLDITCKDMRNLRFAL 80

                         90       100
                 ....*....|....*....|
gi 255958300 124 KQEGHSRRDMFEILVKHAFP 143
Cdd:cd13355   81 KQEGHSRRDIFEILTKYAFP 100
GRAM pfam02893
GRAM domain; The GRAM domain is found in in glucosyltransferases, myotubularins and other ...
 32-143 3.54e-20

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: 85.88  E-value: 3.54e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300   32 SETVPRLPGELLITEkeviYICPFN---GPIKGRVYITNYRLYLRSLETDSALILDVPLGVISRIEKMGGATSRGENSYG 108
Cdd:pfam02893   4 RKKFKLPPEERLIAS----YSCYLNrdgGPVQGRLYLTNYRLCFRSLPKGWSTKVVIPLVDIEEIEKLKGGANLFPNGIQ 79

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 255958300  109 LDITCKDlrNLRFALKQEGHSRRDMFEILVKHAFP 143
Cdd:pfam02893  80 VETGSND--KFSFAGFVTRDEAIEFILALLKNAHP 112
GRAM smart00568
domain in glucosyltransferases, myotubularins and other putative membrane-associated proteins;
38-97 9.19e-12

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


Pssm-ID: 214725 [Multi-domain]  Cd Length: 60  Bit Score: 60.30  E-value: 9.19e-12
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 255958300    38 LPGELLITEkeviYICPFN--GPIKGRVYITNYRLYLRSLETDSALILDVPLGVISRIEKMG 97
Cdd:smart00568   3 PEEEKLIAD----YSCYLSrtGPVQGRLYISNYRLCFRSNLPGKLTKVVIPLADITRIEKST 60
PTPc_motif smart00404
Protein tyrosine phosphatase, catalytic domain motif;
323-471 3.79e-07

Protein tyrosine phosphatase, catalytic domain motif;


Pssm-ID: 214649 [Multi-domain]  Cd Length: 105  Bit Score: 48.51  E-value: 3.79e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300   323 KVKDIVYPNIEESHW-LSSLESTHWLEHIKLVLTGaiqvadqvSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFYRTie 401
Cdd:smart00404   1 TVKHYHYTGWPDHGVpESPDSILELLRAVKKNLNQ--------SESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEA-- 70

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300   402 gfeilvqkewisfghkfasrighgdknhadadrspIFLQFIDCVWQMSKQFPTAFEFNEGFLITVLDHLY 471
Cdd:smart00404  71 -----------------------------------GEVDIFDTVKELRSQRPGMVQTEEQYLFLYRALLE 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: 587.52  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300  162 DGWTVYNPVEEYRRQGLPNH-HWRISFINKCYELCETYPALLVVPYRTSDDDLRRIATFRSRNRLPVLSWIHPENKMVIM 240
Cdd:pfam06602   3 NGWDLYDPEAEFARQGLPSKdEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHKENGAVIT 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300  241 RCSQPLVGMSGKRNKDDEKYLDVIRETNKQTS--KLMIYDARPSVNAVANKATGGGYESDDAYQNSELSFLDIHNIHVMR 318
Cdd:pfam06602  83 RSSQPLVGLNGKRSIEDEKLLQAIFKSSNPYSakKLYIVDARPKLNAMANRAKGGGYENEDNYPNCKKIFLGIENIHVMR 162

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300  319 ESLKKVKDIVYP-NIEESHWLSSLESTHWLEHIKLVLTGAIQVADQVSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFY 397
Cdd:pfam06602 163 DSLNKLVEACNDrSPSMDKWLSRLESSGWLKHIKAILDGACLIAQAVDLEGSSVLVHCSDGWDRTAQLTSLAQLLLDPYY 242

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300  398 RTIEGFEILVQKEWISFGHKFASRIGHGDKNHADADRSPIFLQFIDCVWQMSKQFPTAFEFNEGFLITVLDHLYSCRFGT 477
Cdd:pfam06602 243 RTIEGFQVLIEKEWLSFGHKFADRCGHLAGFTDSKERSPVFLQFLDCVWQLLRQFPCAFEFNERFLIRLLYHLYSCQFGT 322

                         330
                  ....*....|..
gi 255958300  478 FLFNCDsaRERQ 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: 556.56  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 223 NRLPVLSWIHPENKMVIMRCSQPLVGMSGKRNKDDEKYLDVIRETNKQTSKLMIYDARPSVNAVANKATGGGYESDDAYQ 302
Cdd:cd14591    1 NRIPVLSWIHPENQAVIMRCSQPLVGMSGKRNKDDEKYLDIIREANGQTSKLTIYDARPSVNAVANKATGGGYEGDDAYQ 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 303 NSELSFLDIHNIHVMRESLKKVKDIVYPNIEESHWLSSLESTHWLEHIKLVLTGAIQVADQVSSGKSSVLVHCSDGWDRT 382
Cdd:cd14591   81 NAELVFLDIHNIHVMRESLKKLKDIVYPNVEESHWLSSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWDRT 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 383 AQLTSLAMLMLDSFYRTIEGFEILVQKEWISFGHKFASRIGHGDKNHADADRSPIFLQFIDCVWQMSKQFPTAFEFNEGF 462
Cdd:cd14591  161 AQLTSLAMLMLDSYYRTIEGFEVLVQKEWISFGHKFASRIGHGDKNHADADRSPIFLQFIDCVWQMSKQFPTAFEFNEQF 240


                 ....*....
gi 255958300 463 LITVLDHLY 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: 520.47  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 223 NRLPVLSWIHPENKMVIMRCSQPLVGMSGKRNKDDEKYLDVIRETNKQTSKLMIYDARPSVNAVANKATGGGYESDDAYQ 302
Cdd:cd14535    1 NRIPVLSWIHPESQATITRCSQPLVGVSGKRSKDDEKYLQLIMDANAQSHKLFIMDARPSVNAVANKAKGGGYESEDAYQ 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 303 NSELSFLDIHNIHVMRESLKKVKDIVYPNIEESHWLSSLESTHWLEHIKLVLTGAIQVADQVSSGKSSVLVHCSDGWDRT 382
Cdd:cd14535   81 NAELVFLDIHNIHVMRESLRKLKDICFPNIDDSHWLSNLESTHWLEHIKLILAGAVRIADKVESGKTSVVVHCSDGWDRT 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 383 AQLTSLAMLMLDSFYRTIEGFEILVQKEWISFGHKFASRIGHGDKNHADADRSPIFLQFIDCVWQMSKQFPTAFEFNEGF 462
Cdd:cd14535  161 AQLTSLAMLMLDPYYRTIRGFEVLIEKEWLSFGHKFAQRIGHGDKNHSDADRSPVFLQFIDCVWQMTRQFPNAFEFNEHF 240


                 ....*....
gi 255958300 463 LITVLDHLY 471
Cdd:cd14535  241 LITILDHLY 249
PTP-MTMR2 cd14590
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 210-471 0e+00

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: 511.12  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 210 DDDLRRIATFRSRNRLPVLSWIHPENKMVIMRCSQPLVGMSGKRNKDDEKYLDVIRETNKQTSKLMIYDARPSVNAVANK 289
Cdd:cd14590    1 DEELKRVASFRSRGRIPVLSWIHPESQATITRCSQPMVGVSGKRSKEDEKYLQAIMDSNAQSHKIFIFDARPSVNAVANK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 290 ATGGGYESDDAYQNSELSFLDIHNIHVMRESLKKVKDIVYPNIEESHWLSSLESTHWLEHIKLVLTGAIQVADQVSSGKS 369
Cdd:cd14590   81 AKGGGYESEDAYQNAELVFLDIHNIHVMRESLRKLKEIVYPNIEESHWLSNLESTHWLEHIKLILAGALRIADKVESGKT 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 370 SVLVHCSDGWDRTAQLTSLAMLMLDSFYRTIEGFEILVQKEWISFGHKFASRIGHGDKNHADADRSPIFLQFIDCVWQMS 449
Cdd:cd14590  161 SVVVHCSDGWDRTAQLTSLAMLMLDGYYRTIRGFEVLVEKEWLSFGHRFQLRVGHGDKNHADADRSPVFLQFIDCVWQMT 240

                        250       260
                 ....*....|....*....|..
gi 255958300 450 KQFPTAFEFNEGFLITVLDHLY 471
Cdd:cd14590  241 RQFPTAFEFNEYFLITILDHLY 262
PTP-MTMR1 cd14592
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 224-471 3.22e-152

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: 437.87  E-value: 3.22e-152
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 224 RLPVLSWIHPENKMVIMRCSQPLVGMSGKRNKDDEKYLDVIRETNKQTSKLMIYDARPSVNAVANKATGGGYESDDAYQN 303
Cdd:cd14592    2 RVPVLSWIHPESQATITRCSQPLVGPNDKRCKEDEKYLQTIMDANAQSHKLIIFDARQNSVADTNKTKGGGYESESAYPN 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 304 SELSFLDIHNIHVMRESLKKVKDIVYPNIEESHWLSSLESTHWLEHIKLVLTGAIQVADQVSSGKSSVLVHCSDGWDRTA 383
Cdd:cd14592   82 AELVFLEIHNIHVMRESLRKLKEIVYPSIDEARWLSNVDGTHWLEYIRMLLAGAVRIADKIESGKTSVVVHCSDGWDRTA 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 384 QLTSLAMLMLDSFYRTIEGFEILVQKEWISFGHKFASRIGHGDKNHADADRSPIFLQFIDCVWQMSKQFPTAFEFNEGFL 463
Cdd:cd14592  162 QLTSLAMLMLDSYYRTIKGFEVLIEKEWISFGHRFALRVGHGDDNHADADRSPIFLQFIDCVWQMTRQFPSAFEFNELFL 241


                 ....*...
gi 255958300 464 ITVLDHLY 471
Cdd:cd14592  242 ITILDHLY 249
PTP-MTM-like cd14507
protein tyrosine phosphatase-like domain of myotubularins; Myotubularins are a unique subgroup ...
 223-447 3.07e-142

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: 411.56  E-value: 3.07e-142
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 223 NRLPVLSWIHPENKMVIMRCSQPLVGMSGKRNKDDEKYLDVIRETNKQTSKLMIYDARPSVNAVANKATGGGYESDDAYQ 302
Cdd:cd14507    1 GRIPVLSWRHPRNGAVICRSSQPLVGLTGSRSKEDEKLLNAIRKASPSSKKLYIVDARPKLNAVANRAKGGGYENTEYYP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 303 NSELSFLDIHNIHVMRESLKKVKDIVY-PNIEESHWLSSLESTHWLEHIKLVLTGAIQVADQVSSGKSSVLVHCSDGWDR 381
Cdd:cd14507   81 NCELEFLNIENIHAMRDSLNKLRDACLsPNDEESNWLSALESSGWLEHIRLILKGAVRVADLLEKEGTSVLVHCSDGWDR 160

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 255958300 382 TAQLTSLAMLMLDSFYRTIEGFEILVQKEWISFGHKFASRIGHGDKNHADADRSPIFLQFIDCVWQ 447
Cdd:cd14507  161 TSQLTSLAQLLLDPYYRTIEGFQVLIEKEWLSFGHKFADRCGHGDKNSSDEERSPIFLQFLDCVWQ 226
PTP-MTMR6-like cd14532
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases ...
 169-472 2.76e-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: 404.42  E-value: 2.76e-138
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 169 PVEEYRRQGLPNHHWRISFINKCYELCETYPALLVVPYRTSDDDLRRIATFRSRNRLPVLSWIHPENKMVIMRCSQPLVG 248
Cdd:cd14532    1 LESEYTRMGVPNDNWTLSDINKDYELCDTYPRELFVPTSASTPVLVGSSKFRSKGRLPVLSYLHKDNQAAICRCSQPLSG 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 249 MSGkRNKDDEKYLDVIRETNKQTSKLMIYDARPSVNAVANKATGGGYESDDAYQNSELSFLDIHNIHVMRESLKKVKDIV 328
Cdd:cd14532   81 FSA-RCVEDEQLLQAIRKANPNSKFMYVVDTRPKINAMANKAAGKGYENEDNYSNIKFQFFGIENIHVMRSSLQKLLEVC 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 329 -YPNIEESHWLSSLESTHWLEHIKLVLTGAIQVADQVSSGkSSVLVHCSDGWDRTAQLTSLAMLMLDSFYRTIEGFEILV 407
Cdd:cd14532  160 eLKNPSMSAFLSGLESSGWLKHIKAVMDTSVFIAKAVSEG-ASVLVHCSDGWDRTAQTCSLASLLLDPYYRTIKGFQVLI 238

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 255958300 408 QKEWISFGHKFASRIGHGDKNHADAdrSPIFLQFIDCVWQMSKQFPTAFEFNEGFLITVLDHLYS 472
Cdd:cd14532  239 EKEWLSFGHKFTDRCGHLQGDAKEV--SPVFTQFLDCVWQLMQQFPRAFEFNERFLLTLHDHVYS 301
PTP-MTMR8 cd14584
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 163-472 8.84e-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: 352.25  E-value: 8.84e-118
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 163 GWTVYNPVEEYRRQGLPNHHWRISFINKCYELCETYPALLVVPYRTSDDDLRRIATFRSRNRLPVLSWIHPENKMVIMRC 242
Cdd:cd14584    1 GWKLIDLKVDFQRMGIPNDYWEITDANKNYEICSTYPPELVVPKSASKATVVGSSKFRSRGRFPVLSYLYKENNAAICRC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 243 SQPLVGMSGkRNKDDEKYLDVIRETNKQTSKLMIYDARPSVNAVANKATGGGYESDDAYQNSELSFLDIHNIHVMRESLK 322
Cdd:cd14584   81 SQPLSGFSA-RCVEDEQMLQAISKANPGSPFMYVVDTRPKLNAMANRAAGKGYENEDNYSNIRFQFIGIENIHVMRSSLQ 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 323 K---VKDIVYPNIeeSHWLSSLESTHWLEHIKLVLTGAIQVADQVSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFYRT 399
Cdd:cd14584  160 KlleVCEMKSPSM--SDFLTGLENSGWLRHIKAVMDAGVFLAKAVKEEKASVLVHCSDGWDRTAQVCSLASLLLDPFYRT 237

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 255958300 400 IEGFEILVQKEWISFGHKFASRIGHGDKNHADAdrSPIFLQFIDCVWQMSKQFPTAFEFNEGFLITVLDHLYS 472
Cdd:cd14584  238 IKGLMVLIEKEWISMGHKFSQRCGHLDGDPKEV--SPVFTQFLECVWQLMEQFPCAFEFNEHFLLEIHDHVFS 308
PTP-MTMR6 cd14585
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 171-472 2.85e-110

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: 332.66  E-value: 2.85e-110
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 171 EEYRRQGLPNHHWRISFINKCYELCETYPALLVVPYRTSDDDLRRIATFRSRNRLPVLSWIHPENKMVIMRCSQPLVGMS 250
Cdd:cd14585    3 EEYKRMGVPNDYWQLSDVNRDYKICDTYPRDLYVPITASKPIIVGSSKFRSKGRFPVLSYYHQEKKAAICRCSQPLSGFS 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 251 GkRNKDDEKYLDVIRETNKQTSKLMIYDARPSVNAVANKATGGGYESDDAYQNSELSFLDIHNIHVMRESLKKVKDIV-Y 329
Cdd:cd14585   83 A-RCLEDEHMLQAISKANPNNRYMYVMDTRPKLNAMANRAAGKGYENEDNYSNIRFQFVGIENIHVMRSSLQKLLEVCgT 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 330 PNIEESHWLSSLESTHWLEHIKLVLTGAIQVADQVSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFYRTIEGFEILVQK 409
Cdd:cd14585  162 KALSVNDFLSGLESSGWLRHIKAVLDAAVFLAKAVAVEGASVLVHCSDGWDRTAQVCSLGSLLLDPYYRTIKGFMVLIEK 241

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 255958300 410 EWISFGHKFASRIGHGDKNHADAdrSPIFLQFIDCVWQMSKQFPTAFEFNEGFLITVLDHLYS 472
Cdd:cd14585  242 DWISFGHKFSDRCGQLDGDPKEI--SPVFTQFLECVWQLTEQFPRAFEFSEAFLLQIHEHIHS 302
PTP-MTMR7 cd14583
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 171-472 7.91e-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: 323.84  E-value: 7.91e-107
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 171 EEYRRQGLPNHHWRISFINKCYELCETYPALLVVPYRTSDDDLRRIATFRSRNRLPVLSWIHPENKMVIMRCSQPLVGMS 250
Cdd:cd14583    3 AEYNRMGLPNSLWQVSDVNRDYRVCDTYPTELYVPKSATAPIIVGSSKFRSRGRFPVLSYYCKDNNASICRSSQPLSGFS 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 251 GkRNKDDEKYLDVIRETNKQTSKLMIYDARPSVNAVANKATGGGYESDDAYQNSELSFLDIHNIHVMRESLKK---VKDI 327
Cdd:cd14583   83 A-RCLEDEQMLQAIRKANPGSDFMYVVDTRPKLNAMANRAAGKGYENEDNYSNIKFQFIGIENIHVMRNSLQKmleVCEL 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 328 VYPNIEESHWlsSLESTHWLEHIKLVLTGAIQVADQVSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFYRTIEGFEILV 407
Cdd:cd14583  162 RSPSMGDFLW--GLENSGWLKHIKAIMDAGIFIAKAVAEEGASVLVHCSDGWDRTAQVCSVASLLLDPYYRTIKGFMVLI 239

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 255958300 408 QKEWISFGHKFASRIGHGDKNHADAdrSPIFLQFIDCVWQMSKQFPTAFEFNEGFLITVLDHLYS 472
Cdd:cd14583  240 EKDWVSFGHKFNHRYGHLDGDPKEV--SPVIDQFIECVWQLMEQFPCAFEFNERFLIHIHHHIYS 302
PTP-MTMR4 cd14587
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 183-447 3.12e-85

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: 268.44  E-value: 3.12e-85
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 183 WRISFINKCYELCETYPALLVVPYRTSDDDLRRIATFRSRNRLPVLSWIHPENKMVIMRCSQPLVGMSGKRNKDDEKYLD 262
Cdd:cd14587    3 WRVSEINSNYKLCSSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLRNGAVIARCSQPEISWWGWRNADDEYLVT 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 263 VI----------RETNKQTS-------------------------------KLMIYDARPSVNAVANKATGGGYESDDAY 301
Cdd:cd14587   83 SIakacaldpgtRAPGGSPSkgnsdgsdasdtdfdssltacsavesgaapqKLLILDARSYTAAVANRAKGGGCECEEYY 162

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 302 QNSELSFLDIHNIHVMRESLKKVKDIVYPNIEESHWLSSLESTHWLEHIKLVLTGAIQVADQVSSGKSSVLVHCSDGWDR 381
Cdd:cd14587  163 PNCEVMFMGMANIHSIRNSFQYLRAVCSQMPDPGNWLSALESTKWLQHLSVMLKAAVLVASAVDREGRPVLVHCSDGWDR 242

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 255958300 382 TAQLTSLAMLMLDSFYRTIEGFEILVQKEWISFGHKFASRIGHGDKNHADADRSPIFLQFIDCVWQ 447
Cdd:cd14587  243 TPQIVALAKILLDPYYRTIEGFQVLVETDWLDFGHKFGDRCGHQENVEDQNEQCPVFLQWLDCVHQ 308
PTP-MTMR3 cd14586
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 180-447 4.34e-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: 265.73  E-value: 4.34e-84
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 180 NHHWRISFINKCYELCETYPALLVVPYRTSDDDLRRIATFRSRNRLPVLSWIHPENKMVIMRCSQPLVGMSGKRNKDDEK 259
Cdd:cd14586    5 QNAWRISNINEKYKLCGSYPQELIVPAWITDKELESVASFRSWKRIPAVVYRHQSNGAVIARCGQPEVSWWGWRNADDEH 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 260 YLDVIRE-------------------------------------TNK--------QTSKLMIYDARPSVNAVANKATGGG 294
Cdd:cd14586   85 LVQSVAKacasdssscksvlmtgncsrdfpnggdlsdvefdssmSNAsgveslaiQPQKLLILDARSYAAAVANRAKGGG 164

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 295 YESDDAYQNSELSFLDIHNIHVMRESLKKVKDIVYPNIEESHWLSSLESTHWLEHIKLVLTGAIQVADQVSSGKSSVLVH 374
Cdd:cd14586  165 CECPEYYPNCEVVFMGMANIHSIRKSFQSLRLLCTQMPDPANWLSALESTKWLQHLSMLLKSALLVVHAVDRDQRPVLVH 244

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 255958300 375 CSDGWDRTAQLTSLAMLMLDSFYRTIEGFEILVQKEWISFGHKFASRIGHGDKNHADADRSPIFLQFIDCVWQ 447
Cdd:cd14586  245 CSDGWDRTPQIVALSKLLLDPYYRTIEGFQVLVETEWLDFGHKFADRCGHGENSDDLNERCPVFLQWLDCVHQ 317
PTP-MTMR3-like cd14533
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases ...
 223-447 1.57e-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: 258.49  E-value: 1.57e-82
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 223 NRLPVLSWIHPENKMVIMRCSQPLVGMSGKRNKDDEKYLDVIRET---NKQTSKLMIYDARPSVNAVANKATGGGYESDD 299
Cdd:cd14533    2 KRIPSVVWRHQRNGAVIARCSQPEVGWLGWRNAEDENLLQAIAEAcasNASPKKLLIVDARSYAAAVANRAKGGGCECPE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 300 AYQNSELSFLDIHNIHVMRESLKKVKDIVYPNIEESHWLSSLESTHWLEHIKLVLTGAIQVADQVSSGKSSVLVHCSDGW 379
Cdd:cd14533   82 YYPNCEVVFMNLANIHAIRKSFHSLRALCSSAPDQPNWLSNLESTKWLHHLSGLLKAALLVVNAVDEEGRPVLVHCSDGW 161

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 255958300 380 DRTAQLTSLAMLMLDSFYRTIEGFEILVQKEWISFGHKFASRIGHGDKNHADADRSPIFLQFIDCVWQ 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 9.34e-81

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: 253.91  E-value: 9.34e-81
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 223 NRLPVLSWIHPENKMVIMRCSQPLVGMSGKRNKDDEKYLDVI-----RETNKQTSKLMIYDARPSVNAVANKATGGGYES 297
Cdd:cd17666    1 QRIPVLTYLHKANGCSITRSSQPLVGLKQNRSIQDEKLVSEIfntsiNEIYISPQKNLIVDARPTTNAMAQVALGAGTEN 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 298 DDAYQNSELS--FLDIHNIHVMRESLKKVKDIV----YPNIEESHWLSSLESTHWLEHIKLVLTGAIQVADQVSSGKSSV 371
Cdd:cd17666   81 MDNYKYKTAKkiYLGIDNIHVMRDSLNKVTEALkdgdDSNPSYPPLINALKKSNWLKYLAIILQGADLIAKSIHFNHSHV 160

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 255958300 372 LVHCSDGWDRTAQLTSLAMLMLDSFYRTIEGFEILVQKEWISFGHKFASRIGHGDKnhadadrSPIFLQFIDCVWQ 447
Cdd:cd17666  161 LIHCSDGWDRTSQLSALAQLCLDPYYRTLEGFMVLVEKDWLSFGHRFAERSGHKET-------SPVFHQFLDCVYQ 229
PH-GRAM_MTM1 cd13355
Myotubularian 1 protein (MTM1) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase ...
 44-143 2.07e-67

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: 214.33  E-value: 2.07e-67
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300  44 ITEKEVIYICPFNGPIKGRVYITNYRLYLRSLETDSALILDVPLGVISRIEKMGGATSRGENSYGLDITCKDLRNLRFAL 123
Cdd:cd13355    1 VTDKDVIYICPFNGPVKGRVYITNYRLYFKSTESEPPVTLDVPLGVISRIEKMGGASSRGENSYGLDITCKDMRNLRFAL 80

                         90       100
                 ....*....|....*....|
gi 255958300 124 KQEGHSRRDMFEILVKHAFP 143
Cdd:cd13355   81 KQEGHSRRDIFEILTKYAFP 100
PTP-MTMR9 cd14536
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 224-447 3.35e-63

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: 207.58  E-value: 3.35e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 224 RLPVLSWIHPENKMVIMRCSQPLVGMSGKRNKDDEKYLDVIRETNKqtsKLMIYDARPSVNAVANKATGGGYESDDAYQN 303
Cdd:cd14536    2 RFPVLSYYHKKNGMVLMRSSQPLTGPNGKRCKEDEKLLNAVLGGGK---RGYIIDTRSKNVAQQARAKGGGFEPEAHYPQ 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 304 SELSFLDIHNIHVMRESLKK-VKDIVYPNIEESHWLSSLESTHWLEHIKLVLTGAIQVADQVSSGKSSVLVHCSDGWDRT 382
Cdd:cd14536   79 WRRIHKPIERYNVLQESLIKlVEACNDQGHSMDKWLSKLESSNWLSHVKEILTTACLVAQCIDREGASVLVHGSEGMDST 158

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 255958300 383 AQLTSLAMLMLDSFYRTIEGFEILVQKEWISFGHKFASRIGHGDKNHA-DADRSPIFLQFIDCVWQ 447
Cdd:cd14536  159 LQVTSLAQIILDPDCRTIRGFEALIEREWLQAGHPFQSRCAKSAYSNSkQKFESPVFLLFLDCVWQ 224
PTP-MTMR5-like cd14534
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 183-451 1.46e-57

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: 194.51  E-value: 1.46e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 183 WRISFINKCYELCETYPALLVVPYRTSDDDLRRIATFRSRNRLPVLSWIHPENKMVIMRCSQP----LVGM--------- 249
Cdd:cd14534    1 FRISTANRDYSICRSYPALVVVPQSVSDESLRKVARCYRQGRFPVVTWRHPRTKALLLRSGGFhgkgVMGMlksantsts 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 250 SGKRNKDD-------EKYLdviretnkqtSKLMIYdarpsvnAVANKATGGGYESDdAYQNSELSFLDIHNIHVMRESLK 322
Cdd:cd14534   81 SPTVSSSEtsssleqEKYL----------SALVLY-------VLGEKSQMKGVKAE-SDPKCEFIPVEYPEVRQVKASFK 142

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 323 KVKDIVYPNI----EESHWLSSLESTHWLEHIKLVLTGAIQVADQVSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFYR 398
Cdd:cd14534  143 KLLRACVPSSaptePEQSFLKAVEDSEWLQQLQCLMQLSGAVVDLLDVQGSSVLLCLEDGWDVTTQVSSLSQLLLDPYYR 222

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|...
gi 255958300 399 TIEGFEILVQKEWISFGHKFASRiGHGDKNHADADRSPIFLQFIDCVWQMSKQ 451
Cdd:cd14534  223 TLEGFRVLVEKEWLAFGHRFSHR-SNLTAASQSSGFAPVFLQFLDAVHQIHRQ 274
PH-GRAM_MTM-like cd13223
Myotubularian 1 and related proteins Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase; ...
 44-143 2.15e-57

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: 187.83  E-value: 2.15e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300  44 ITEKEVIYICPFNGPIKGRVYITNYRLYLRSLETDSALILDVPLGVISRIEKMGGATSRGENSYGLDITCKDLRNLRFAL 123
Cdd:cd13223    1 LKEKDVTYLCPFRGPVRGTLYITNYRLYFKSRDREPNFVLDVPLGVISRVEKVGGATSRGENSYGLEIHCKDMRNLRFAH 80

                         90       100
                 ....*....|....*....|
gi 255958300 124 KQEGHSRRDMFEILVKHAFP 143
Cdd:cd13223   81 KQENHSRRKLYETLQKYAFP 100
PTP-MTMR13 cd14589
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 183-451 1.40e-50

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: 176.65  E-value: 1.40e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 183 WRISFINKCYELCETYPALLVVPYRTSDDDLRRIATFRSRNRLPVLSWIHPENKMVIMRC----SQPLVGMSGKRNK--- 255
Cdd:cd14589    1 FRITAVNRMYSLCRSYPGLLVVPQSVQDSSLQKVARCYRHNRLPVVCWKNSKTKAVLLRSggfhGKGVVGLFKSQNPhsa 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 256 -----------DDEKYLDVIRETNKQTSKL---------MIYDARPSVNAVANKATGGGYESDDAYqNSELSFLDIHNIH 315
Cdd:cd14589   81 apassessssiEQEKYLQALLNAISVHQKMngnstllqsQLLKRQAALYIFGEKSQLRGFKLDFAL-NCEFVPVEFHDIR 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 316 VMRESLKKVKDIVYPNI----EESHWLSSLESTHWLEHIKLVLTGAIQVADQVSSGkSSVLVHCSDGWDRTAQLTSLAML 391
Cdd:cd14589  160 QVKASFKKLMRACVPSTiptdSEVTFLKALGESEWFLQLHRIMQLAVVISELLESG-SSVMVCLEDGWDITTQVVSLVQL 238

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 392 MLDSFYRTIEGFEILVQKEWISFGHKFASRiGHGDKNHADADRSPIFLQFIDCVWQMSKQ 451
Cdd:cd14589  239 LSDPFYRTLEGFQMLVEKEWLSFGHKFSQR-SNLTPNSQGSGFAPIFLQFLDCVHQIHNQ 297
PH-GRAM_MTMR2_insect-like cd13357
Myotubularian related 2 protein (MTMR2) Pleckstrin Homology-Glucosyltransferases, Rab-like ...
 45-143 3.08e-49

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: 166.14  E-value: 3.08e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300  45 TEKEVIYICPFNGPIKGRVYITNYRLYLRSLETDSALILDVPLGVISRIEKMGGATSRGENSYGLDITCKDLRNLRFALK 124
Cdd:cd13357    2 IAKDVTYLCPFRGPVRGTLTITNYKLYFKSLDREPPFTVEVPLGVIYRVEKVGGATSRGENSYGLEIFCKDMRNLRFAHK 81

                         90
                 ....*....|....*....
gi 255958300 125 QEGHSRRDMFEILVKHAFP 143
Cdd:cd13357   82 QENHSRRLVFEKLQAYAFP 100
PTP-MTMR5 cd14588
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 183-451 6.13e-48

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: 169.38  E-value: 6.13e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 183 WRISFINKCYELCETYPALLVVPYRTSDDDLRRIATFRSRNRLPVLSWIHPENKMVIMRC----SQPLVGMSGKRNK--- 255
Cdd:cd14588    1 FRISTVNRMYAVCRSYPGLLIVPQSIQDNTIQRISRCYRQNRFPVVCWRNSRTKAVLLRSgglhGKGVVGLFKSQNApaa 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 256 ----------DDEKYLDVIRET----NKQTSKLMIYDARPSVNAVANKATGGGYESDdAYQNSELSFLDIHNIHVMRESL 321
Cdd:cd14588   81 gqsqtdstslEQEKYLQAVINSmpryADASGRNTLSGFRAALYIIGDKSQLKGVKQD-PLQQWEVVPIEVFDVRQVKASF 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 322 KKVKDIVYPNIEES----HWLSSLESTHWLEHIKLVLTGAIQVADQVSSGkSSVLVHCSDGWDRTAQLTSLAMLMLDSFY 397
Cdd:cd14588  160 KKLMKACVPSCPSTdpsqTYLRTLEESEWLSQLHKLLQVSVLVVELLDSG-SSVLVSLEDGWDITTQVVSLVQLLSDPYY 238

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 255958300 398 RTIEGFEILVQKEWISFGHKFASRIGHGDKNHADAdRSPIFLQFIDCVWQMSKQ 451
Cdd:cd14588  239 RTIEGFRLLVEKEWLSFGHRFSHRGAQTLASQSSG-FTPVFLQFLDCVHQIHLQ 291
PH-GRAM_MTMR2_mammal-like cd13356
Myotubularian related 2 protein (MTMR2) Pleckstrin Homology-Glucosyltransferases, Rab-like ...
 33-145 2.58e-44

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: 153.31  E-value: 2.58e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300  33 ETVPRLPGELLI-TEKEVIYICPFNGPIKGRVYITNYRLYLRSLETDSALILDVPLGVISRIEKMGGATSRGENSYGLDI 111
Cdd:cd13356    2 EEPPLLPGENIKdMAKDVTYICPFTGAVRGTLTVTNYRLYFKSMERDPPFVLDASLGVINRVEKIGGASSRGENSYGLET 81

                         90       100       110
                 ....*....|....*....|....*....|....
gi 255958300 112 TCKDLRNLRFALKQEGHSRRDMFEILVKHAFPLA 145
Cdd:cd13356   82 VCKDIRNLRFAHKPEGRTRRSIFENLMKYAFPVS 115
PH-GRAM_MTMR1 cd13358
Myotubularian related 1 protein (MTMR1) Pleckstrin Homology-Glucosyltransferases, Rab-like ...
 45-143 7.28e-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: 135.42  E-value: 7.28e-38
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300  45 TEKEVIYICPFNGPIKGRVYITNYRLYLRSLETDSALILDVPLGVISRIEKMgGATSRGENSYGLDITCKDLRNLRFALK 124
Cdd:cd13358    3 IVKDVMYICPFMGAVSGTLTVTDFKMYFKNVERDPPFILDVPLGVISRVEKI-GVQSHGDNSCGIEIVCKDMRNLRLAYK 81

                         90
                 ....*....|....*....
gi 255958300 125 QEGHSRRDMFEILVKHAFP 143
Cdd:cd13358   82 QEEQSKLEIFENLNKHAFP 100
PTP-MTMR10-like cd14537
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 223-447 1.36e-36

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: 135.55  E-value: 1.36e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 223 NRLPVLSWIHPeNKMVIMRCS--QPLVGMSgkrnKDDEKYLDVIRETNKQTSKLMIYDarPSVNAVANKATGGGYESDda 300
Cdd:cd14537    1 GRPPVWCWSHP-NGAALVRMAelLPTITDR----TQENKMLEAIRKSHPNLKKPKVID--LDKLLPSLQDVQAAYLKL-- 71

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 301 yqnSELSFLDihnihvmreSLKKVKDIvypnieESHWLSSLESTHWLEHIKLVLTGAIQVADQVSSGKSSVLVHCSDGWD 380
Cdd:cd14537   72 ---RELCTPD---------SSEQFWVQ------DSKWYSLLENTKWLHYVSACLKKASEAAEALESRGRSVVLQESDGRD 133

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 255958300 381 RTAQLTSLAMLMLDSFYRTIEGFEILVQKEWISFGHKFASRIGHGDKNHADADRSPIFLQFIDCVWQ 447
Cdd:cd14537  134 LSCVVSSLVQLLLDPHFRTITGFQSLIQKEWVALGHPFCDRLGHVKPNKTESEESPVFLLFLDCVWQ 200
PTP-MTMR11 cd14595
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 337-448 7.67e-30

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: 116.47  E-value: 7.67e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 337 WLSSLESTHWLEHIKLVLTGAIQVADQVSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFYRTIEGFEILVQKEWISFGH 416
Cdd:cd14595   86 WLSNLEGTRWLDHVRACLRKASEVSCLLAERHRSVILQESEDRDLNCLLSSLVQLLSDPHARTISGFQSLVQKEWVVAGH 165

                         90       100       110
                 ....*....|....*....|....*....|...
gi 255958300 417 KFASRIG-HGDknhADADRSPIFLQFIDCVWQM 448
Cdd:cd14595  166 PFLQRLNlTRE---SDKEESPVFLLFLDCVWQL 195
PTP-MTMR12 cd14594
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 337-448 3.59e-27

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: 109.16  E-value: 3.59e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 337 WLSSLESTHWLEHIKLVLTGAIQVADQVSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFYRTIEGFEILVQKEWISFGH 416
Cdd:cd14594   94 WFSSLESSNWLEIIRQCLKKAVEVVECLEKQNTNVLLTEEEATDLCCVISSLVQIMMDPYCRTKSGFQSLIQKEWVMGGH 173

                         90       100       110
                 ....*....|....*....|....*....|..
gi 255958300 417 KFASRIGHGDKNhaDADRSPIFLQFIDCVWQM 448
Cdd:cd14594  174 CFLDRCNHLRQN--DKEEVPVFLLFLDCVWQL 203
PTP-MTMR10 cd14593
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 224-447 5.52e-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: 108.44  E-value: 5.52e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 224 RLPVLSWIHPE-NKMVIMRCSQPLVgmsgKRNKDDEKYLDVIRETNKQTSKLmiydarpsvnavankatgggYESDdayq 302
Cdd:cd14593    2 RIPLWCWNHPNgSALVRMANIKDLL----QQRKIDQRICNAITRSHPLRSDV--------------------YKSD---- 53

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 303 nselsfLD--IHNIHVMRESLKKVKDI-VYPNIEESH--WLSSLESTHWLEHIKLVLTGAIQVADQVSSGKSSVLVHCSD 377
Cdd:cd14593   54 ------LDktLPNIQEIQAAFVKLKQLcVNEPFEETEekWLSSLESTRWLEYVRAFLKHSAELVYMLESKHVSVILQEEE 127

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300 378 GWDRTAQLTSLAMLMLDSFYRTIEGFEILVQKEWISFGHKFASRIGHGDKnhADADRSPIFLQFIDCVWQ 447
Cdd:cd14593  128 GRDLSCVVASLVQVMLDPYFRTITGFQSLIQKEWVMAGYRFLDRCNHLKK--SSKKESPLFLLFLDCVWQ 195
GRAM pfam02893
GRAM domain; The GRAM domain is found in in glucosyltransferases, myotubularins and other ...
 32-143 3.54e-20

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: 85.88  E-value: 3.54e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300   32 SETVPRLPGELLITEkeviYICPFN---GPIKGRVYITNYRLYLRSLETDSALILDVPLGVISRIEKMGGATSRGENSYG 108
Cdd:pfam02893   4 RKKFKLPPEERLIAS----YSCYLNrdgGPVQGRLYLTNYRLCFRSLPKGWSTKVVIPLVDIEEIEKLKGGANLFPNGIQ 79

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 255958300  109 LDITCKDlrNLRFALKQEGHSRRDMFEILVKHAFP 143
Cdd:pfam02893  80 VETGSND--KFSFAGFVTRDEAIEFILALLKNAHP 112
PH-GRAM cd10570
Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins ...
 47-137 2.02e-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: 66.25  E-value: 2.02e-13
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300  47 KEVIYICPFNGPIKGRVYITNYRLYLRSLETDSALILDVPLGVISRIEKMGGATSrgeNSYGLDITCKDLRNLRFALKQE 126
Cdd:cd10570    7 RFCCALRPRKLPLEGTLYLSTYRLIFSSKADGDETKLVIPLVDITDVEKIAGASF---LPSGLIITCKDFRTIKFSFDSE 83

                         90
                 ....*....|.
gi 255958300 127 GHSRRDMFEIL 137
Cdd:cd10570   84 DEAVKVIARVL 94
GRAM smart00568
domain in glucosyltransferases, myotubularins and other putative membrane-associated proteins;
38-97 9.19e-12

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


Pssm-ID: 214725 [Multi-domain]  Cd Length: 60  Bit Score: 60.30  E-value: 9.19e-12
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 255958300    38 LPGELLITEkeviYICPFN--GPIKGRVYITNYRLYLRSLETDSALILDVPLGVISRIEKMG 97
Cdd:smart00568   3 PEEEKLIAD----YSCYLSrtGPVQGRLYISNYRLCFRSNLPGKLTKVVIPLADITRIEKST 60
PTPc_motif smart00404
Protein tyrosine phosphatase, catalytic domain motif;
323-471 3.79e-07

Protein tyrosine phosphatase, catalytic domain motif;


Pssm-ID: 214649 [Multi-domain]  Cd Length: 105  Bit Score: 48.51  E-value: 3.79e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300   323 KVKDIVYPNIEESHW-LSSLESTHWLEHIKLVLTGaiqvadqvSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFYRTie 401
Cdd:smart00404   1 TVKHYHYTGWPDHGVpESPDSILELLRAVKKNLNQ--------SESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEA-- 70

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300   402 gfeilvqkewisfghkfasrighgdknhadadrspIFLQFIDCVWQMSKQFPTAFEFNEGFLITVLDHLY 471
Cdd:smart00404  71 -----------------------------------GEVDIFDTVKELRSQRPGMVQTEEQYLFLYRALLE 105
PTPc_DSPc smart00012
Protein tyrosine phosphatase, catalytic domain, undefined specificity; Protein tyrosine ...
 323-471 3.79e-07

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: 48.51  E-value: 3.79e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300   323 KVKDIVYPNIEESHW-LSSLESTHWLEHIKLVLTGaiqvadqvSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSFYRTie 401
Cdd:smart00012   1 TVKHYHYTGWPDHGVpESPDSILELLRAVKKNLNQ--------SESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEA-- 70

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300   402 gfeilvqkewisfghkfasrighgdknhadadrspIFLQFIDCVWQMSKQFPTAFEFNEGFLITVLDHLY 471
Cdd:smart00012  71 -----------------------------------GEVDIFDTVKELRSQRPGMVQTEEQYLFLYRALLE 105
PTP_DSP_cys cd14494
cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This ...
 354-422 1.96e-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: 43.88  E-value: 1.96e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 255958300 354 LTGAIQVADQVSSGKSSVLVHCSDGWDRTAQLTSLAMLMldsfyRTIEGFEILVQKEWISFGHKFASRI 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 1.07e-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: 38.53  E-value: 1.07e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255958300  49 VIYICPFNGPIKGRVYITNYRLYLRSlETDSALILDVPLGVISRIEKmggaTSRGENSYGLDITCKDLRN-LRFALKQEG 127
Cdd:cd00900    6 VRVYREPTKRVEGTLYITSDRLILRD-KNDGGLELSIPISDIVNVNV----SPQGPSSRYLVLVLKDRGEfVGFSFPKEE 80


                 ....
gi 255958300 128 HSRR 131
Cdd:cd00900   81 DAIE 84
DSP_DUSP4 cd14640
dual specificity phosphatase domain of dual specificity protein phosphatase 4; Dual ...
 357-412 5.70e-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: 37.71  E-value: 5.70e-03
                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 255958300 357 AIQVADQVSSGKSSVLVHCSDGWDRTAQLTsLAMLMLDSFYRTIEGFEILVQKEWI 412
Cdd:cd14640   67 AIEYIDSVKDCNGRVLVHCQAGISRSATIC-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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