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Conserved domains on  [gi|34784179|gb|AAH58091|]
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Mtmr4 protein [Mus musculus]

Protein Classification

PH domain-containing protein; PH domain-containing RhoGEF family protein( domain architecture ID 13117787)

Pleckstrin homology (PH) domain-containing protein may be involved in targeting a protein to the appropriate cellular location or interacting with a binding partner; similar to the PH region of pleckstrin homology domain-containing family A member 2 (PLEKHA2/TAAP2) that binds specifically to phosphatidylinositol 3,4-diphosphate (PtdIns3,4P2)| PH domain-containing RhoGEF family protein may function as a guanine nucleotide exchange factor; similar to Homo sapiens pleckstrin homology domain-containing family G member 4B and Danio rerio quattro

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PTP-MTMR4 cd14587
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
172-479 0e+00

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: 714.50  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 172 NVWRVSHINSNYKLCPSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLRNGAAIARCSQPEISWWGWRNADDEYL 251
Cdd:cd14587   1 NVWRVSEINSNYKLCSSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLRNGAVIARCSQPEISWWGWRNADDEYL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 252 VTSIAKACALDPGTRASGGSLSTGTNDASEACDTDFDSSLTACSGVESTAAPQKLLILDARSYTAAVANRAKGGGCECEE 331
Cdd:cd14587  81 VTSIAKACALDPGTRAPGGSPSKGNSDGSDASDTDFDSSLTACSAVESGAAPQKLLILDARSYTAAVANRAKGGGCECEE 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 332 YYPNCEVLFMGMANIHAIRNSFQYLRAVCSQMPDPSNWLSALESTKWLQHLSVMLKAAVLVANTVDREGRPVLVHCSDGW 411
Cdd:cd14587 161 YYPNCEVMFMGMANIHSIRNSFQYLRAVCSQMPDPGNWLSALESTKWLQHLSVMLKAAVLVASAVDREGRPVLVHCSDGW 240
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 34784179 412 DRTPQIVALAKILLDPYYRTLEGFQVLVESDWLDFGHKFGDRCGHQENAEDQNEQCPVFLQWLDSVHQ 479
Cdd:cd14587 241 DRTPQIVALAKILLDPYYRTIEGFQVLVETDWLDFGHKFGDRCGHQENVEDQNEQCPVFLQWLDCVHQ 308
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
23-136 2.17e-78

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 cd13342:

Pssm-ID: 473070  Cd Length: 114  Bit Score: 249.51  E-value: 2.17e-78
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179  23 LVKEEENLQVPFILLQGEGVEFLGRATDALIAISNYRLHIKFKDSVINVPLRMIDSVESRDMFQLHIACKDSKVVRCHFS 102
Cdd:cd13342   1 LVKEEESLQVPFPVLQGEGVEYLGHANDAVIAISNYRLHIKFKDSVINVPLRMMESVESRDMFQLHIICKDSKVVRCHFS 80
                        90       100       110
                ....*....|....*....|....*....|....
gi 34784179 103 TFKQCQEWLSRLSRATARPAKPEDLFAFAYHAWC 136
Cdd:cd13342  81 TFKQCQEWLKRLNRATARPAKPEDLFAFAYHAWC 114
 
Name Accession Description Interval E-value
PTP-MTMR4 cd14587
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
172-479 0e+00

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: 714.50  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 172 NVWRVSHINSNYKLCPSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLRNGAAIARCSQPEISWWGWRNADDEYL 251
Cdd:cd14587   1 NVWRVSEINSNYKLCSSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLRNGAVIARCSQPEISWWGWRNADDEYL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 252 VTSIAKACALDPGTRASGGSLSTGTNDASEACDTDFDSSLTACSGVESTAAPQKLLILDARSYTAAVANRAKGGGCECEE 331
Cdd:cd14587  81 VTSIAKACALDPGTRAPGGSPSKGNSDGSDASDTDFDSSLTACSAVESGAAPQKLLILDARSYTAAVANRAKGGGCECEE 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 332 YYPNCEVLFMGMANIHAIRNSFQYLRAVCSQMPDPSNWLSALESTKWLQHLSVMLKAAVLVANTVDREGRPVLVHCSDGW 411
Cdd:cd14587 161 YYPNCEVMFMGMANIHSIRNSFQYLRAVCSQMPDPGNWLSALESTKWLQHLSVMLKAAVLVASAVDREGRPVLVHCSDGW 240
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 34784179 412 DRTPQIVALAKILLDPYYRTLEGFQVLVESDWLDFGHKFGDRCGHQENAEDQNEQCPVFLQWLDSVHQ 479
Cdd:cd14587 241 DRTPQIVALAKILLDPYYRTIEGFQVLVETDWLDFGHKFGDRCGHQENVEDQNEQCPVFLQWLDCVHQ 308
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
160-496 1.96e-171

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: 500.47  E-value: 1.96e-171
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179   160 EAELARMGFDLQNVWRVSHINSNYKLCPSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLRNGAAIARCSQPEIS 239
Cdd:pfam06602  11 EAEFARQGLPSKDEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHKENGAVITRSSQPLVG 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179   240 WWGWRNADDEYLVTSIAKACaldpgtrasggslstgtndaseacdtdfdssltacsgveSTAAPQKLLILDARSYTAAVA 319
Cdd:pfam06602  91 LNGKRSIEDEKLLQAIFKSS---------------------------------------NPYSAKKLYIVDARPKLNAMA 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179   320 NRAKGGGCECEEYYPNCEVLFMGMANIHAIRNSFQYLRAVCS-QMPDPSNWLSALESTKWLQHLSVMLKAAVLVANTVDR 398
Cdd:pfam06602 132 NRAKGGGYENEDNYPNCKKIFLGIENIHVMRDSLNKLVEACNdRSPSMDKWLSRLESSGWLKHIKAILDGACLIAQAVDL 211
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179   399 EGRPVLVHCSDGWDRTPQIVALAKILLDPYYRTLEGFQVLVESDWLDFGHKFGDRCGHQENAEDQNEQCPVFLQWLDSVH 478
Cdd:pfam06602 212 EGSSVLVHCSDGWDRTAQLTSLAQLLLDPYYRTIEGFQVLIEKEWLSFGHKFADRCGHLAGFTDSKERSPVFLQFLDCVW 291
                         330
                  ....*....|....*...
gi 34784179   479 QLLKQFPCLFEFNEAFLV 496
Cdd:pfam06602 292 QLLRQFPCAFEFNERFLI 309
PH-GRAM_MTMR4 cd13342
Myotubularian (MTM) related 4 protein (MTMR4) Pleckstrin Homology-Glucosyltransferases, ...
23-136 2.17e-78

Myotubularian (MTM) related 4 protein (MTMR4) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR4 is a member of the myotubularin dual specificity protein phosphatase gene family. MTMR4 binds to phosphoinositide lipids through its PH-GRAM domain, and can hydrolyze phosphatidylinositol(3)-phosphate and phosphatidylinositol(3,5)-biphosphate in vitro. The protein form heteromers with MTMR3. Both MTMR3 and MTMR4 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 lipid-binding FYVE domain which binds phosphotidylinositol-3-phosphate. 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: 270150  Cd Length: 114  Bit Score: 249.51  E-value: 2.17e-78
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179  23 LVKEEENLQVPFILLQGEGVEFLGRATDALIAISNYRLHIKFKDSVINVPLRMIDSVESRDMFQLHIACKDSKVVRCHFS 102
Cdd:cd13342   1 LVKEEESLQVPFPVLQGEGVEYLGHANDAVIAISNYRLHIKFKDSVINVPLRMMESVESRDMFQLHIICKDSKVVRCHFS 80
                        90       100       110
                ....*....|....*....|....*....|....
gi 34784179 103 TFKQCQEWLSRLSRATARPAKPEDLFAFAYHAWC 136
Cdd:cd13342  81 TFKQCQEWLKRLNRATARPAKPEDLFAFAYHAWC 114
PTPc_motif smart00404
Protein tyrosine phosphatase, catalytic domain motif;
402-433 7.99e-06

Protein tyrosine phosphatase, catalytic domain motif;


Pssm-ID: 214649 [Multi-domain]  Cd Length: 105  Bit Score: 45.43  E-value: 7.99e-06
                           10        20        30
                   ....*....|....*....|....*....|..
gi 34784179    402 PVLVHCSDGWDRTPQIVALAKILLDPYYRTLE 433
Cdd:smart00404  41 PVVVHCSAGVGRTGTFVAIDILLQQLEAEAGE 72
 
Name Accession Description Interval E-value
PTP-MTMR4 cd14587
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
172-479 0e+00

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: 714.50  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 172 NVWRVSHINSNYKLCPSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLRNGAAIARCSQPEISWWGWRNADDEYL 251
Cdd:cd14587   1 NVWRVSEINSNYKLCSSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLRNGAVIARCSQPEISWWGWRNADDEYL 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 252 VTSIAKACALDPGTRASGGSLSTGTNDASEACDTDFDSSLTACSGVESTAAPQKLLILDARSYTAAVANRAKGGGCECEE 331
Cdd:cd14587  81 VTSIAKACALDPGTRAPGGSPSKGNSDGSDASDTDFDSSLTACSAVESGAAPQKLLILDARSYTAAVANRAKGGGCECEE 160
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 332 YYPNCEVLFMGMANIHAIRNSFQYLRAVCSQMPDPSNWLSALESTKWLQHLSVMLKAAVLVANTVDREGRPVLVHCSDGW 411
Cdd:cd14587 161 YYPNCEVMFMGMANIHSIRNSFQYLRAVCSQMPDPGNWLSALESTKWLQHLSVMLKAAVLVASAVDREGRPVLVHCSDGW 240
                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 34784179 412 DRTPQIVALAKILLDPYYRTLEGFQVLVESDWLDFGHKFGDRCGHQENAEDQNEQCPVFLQWLDSVHQ 479
Cdd:cd14587 241 DRTPQIVALAKILLDPYYRTIEGFQVLVETDWLDFGHKFGDRCGHQENVEDQNEQCPVFLQWLDCVHQ 308
PTP-MTMR3 cd14586
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
167-479 0e+00

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: 580.82  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 167 GFDLQNVWRVSHINSNYKLCPSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLRNGAAIARCSQPEISWWGWRNA 246
Cdd:cd14586   1 GFDMQNAWRISNINEKYKLCGSYPQELIVPAWITDKELESVASFRSWKRIPAVVYRHQSNGAVIARCGQPEVSWWGWRNA 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 247 DDEYLVTSIAKACALDpgTRASGGSLSTGT-----NDASEACDTDFDSSLTACSGVESTA-APQKLLILDARSYTAAVAN 320
Cdd:cd14586  81 DDEHLVQSVAKACASD--SSSCKSVLMTGNcsrdfPNGGDLSDVEFDSSMSNASGVESLAiQPQKLLILDARSYAAAVAN 158
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 321 RAKGGGCECEEYYPNCEVLFMGMANIHAIRNSFQYLRAVCSQMPDPSNWLSALESTKWLQHLSVMLKAAVLVANTVDREG 400
Cdd:cd14586 159 RAKGGGCECPEYYPNCEVVFMGMANIHSIRKSFQSLRLLCTQMPDPANWLSALESTKWLQHLSMLLKSALLVVHAVDRDQ 238
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 34784179 401 RPVLVHCSDGWDRTPQIVALAKILLDPYYRTLEGFQVLVESDWLDFGHKFGDRCGHQENAEDQNEQCPVFLQWLDSVHQ 479
Cdd:cd14586 239 RPVLVHCSDGWDRTPQIVALSKLLLDPYYRTIEGFQVLVETEWLDFGHKFADRCGHGENSDDLNERCPVFLQWLDCVHQ 317
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
160-496 1.96e-171

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: 500.47  E-value: 1.96e-171
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179   160 EAELARMGFDLQNVWRVSHINSNYKLCPSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLRNGAAIARCSQPEIS 239
Cdd:pfam06602  11 EAEFARQGLPSKDEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHKENGAVITRSSQPLVG 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179   240 WWGWRNADDEYLVTSIAKACaldpgtrasggslstgtndaseacdtdfdssltacsgveSTAAPQKLLILDARSYTAAVA 319
Cdd:pfam06602  91 LNGKRSIEDEKLLQAIFKSS---------------------------------------NPYSAKKLYIVDARPKLNAMA 131
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179   320 NRAKGGGCECEEYYPNCEVLFMGMANIHAIRNSFQYLRAVCS-QMPDPSNWLSALESTKWLQHLSVMLKAAVLVANTVDR 398
Cdd:pfam06602 132 NRAKGGGYENEDNYPNCKKIFLGIENIHVMRDSLNKLVEACNdRSPSMDKWLSRLESSGWLKHIKAILDGACLIAQAVDL 211
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179   399 EGRPVLVHCSDGWDRTPQIVALAKILLDPYYRTLEGFQVLVESDWLDFGHKFGDRCGHQENAEDQNEQCPVFLQWLDSVH 478
Cdd:pfam06602 212 EGSSVLVHCSDGWDRTAQLTSLAQLLLDPYYRTIEGFQVLIEKEWLSFGHKFADRCGHLAGFTDSKERSPVFLQFLDCVW 291
                         330
                  ....*....|....*...
gi 34784179   479 QLLKQFPCLFEFNEAFLV 496
Cdd:pfam06602 292 QLLRQFPCAFEFNERFLI 309
PTP-MTMR3-like cd14533
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases ...
213-479 3.60e-155

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: 454.55  E-value: 3.60e-155
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 213 WKRIPVVVYRHLRNGAAIARCSQPEISWWGWRNADDEYLVTSIAKACAldpgtrasggslstgtndaseacdtdfdsslt 292
Cdd:cd14533   1 SKRIPSVVWRHQRNGAVIARCSQPEVGWLGWRNAEDENLLQAIAEACA-------------------------------- 48
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 293 acsgveSTAAPQKLLILDARSYTAAVANRAKGGGCECEEYYPNCEVLFMGMANIHAIRNSFQYLRAVCSQMPDPSNWLSA 372
Cdd:cd14533  49 ------SNASPKKLLIVDARSYAAAVANRAKGGGCECPEYYPNCEVVFMNLANIHAIRKSFHSLRALCSSAPDQPNWLSN 122
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 373 LESTKWLQHLSVMLKAAVLVANTVDREGRPVLVHCSDGWDRTPQIVALAKILLDPYYRTLEGFQVLVESDWLDFGHKFGD 452
Cdd:cd14533 123 LESTKWLHHLSGLLKAALLVVNAVDEEGRPVLVHCSDGWDRTPQIVALAELMLDPYYRTIEGFQVLVEREWLDFGHKFAD 202
                       250       260
                ....*....|....*....|....*..
gi 34784179 453 RCGHQENAEDQNEQCPVFLQWLDSVHQ 479
Cdd:cd14533 203 RCGHGVNSEDINERCPVFLQWLDCVHQ 229
PTP-MTM-like cd14507
protein tyrosine phosphatase-like domain of myotubularins; Myotubularins are a unique subgroup ...
214-479 3.34e-121

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: 366.49  E-value: 3.34e-121
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 214 KRIPVVVYRHLRNGAAIARCSQPEISWWGWRNADDEYLVTSIAKACAldpgtrasggslstgtndaseacdtdfdsslta 293
Cdd:cd14507   1 GRIPVLSWRHPRNGAVICRSSQPLVGLTGSRSKEDEKLLNAIRKASP--------------------------------- 47
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 294 csgvestaAPQKLLILDARSYTAAVANRAKGGGCECEEYYPNCEVLFMGMANIHAIRNSFQYLRAVCSQMPDP-SNWLSA 372
Cdd:cd14507  48 --------SSKKLYIVDARPKLNAVANRAKGGGYENTEYYPNCELEFLNIENIHAMRDSLNKLRDACLSPNDEeSNWLSA 119
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 373 LESTKWLQHLSVMLKAAVLVANTVDREGRPVLVHCSDGWDRTPQIVALAKILLDPYYRTLEGFQVLVESDWLDFGHKFGD 452
Cdd:cd14507 120 LESSGWLEHIRLILKGAVRVADLLEKEGTSVLVHCSDGWDRTSQLTSLAQLLLDPYYRTIEGFQVLIEKEWLSFGHKFAD 199
                       250       260
                ....*....|....*....|....*..
gi 34784179 453 RCGHQENAEDQNEQCPVFLQWLDSVHQ 479
Cdd:cd14507 200 RCGHGDKNSSDEERSPIFLQFLDCVWQ 226
PTP-MTMR6-like cd14532
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases ...
160-498 3.52e-108

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: 335.47  E-value: 3.52e-108
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 160 EAELARMGFDLQNvWRVSHINSNYKLCPSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLRNGAAIARCSQPeIS 239
Cdd:cd14532   2 ESEYTRMGVPNDN-WTLSDINKDYELCDTYPRELFVPTSASTPVLVGSSKFRSKGRLPVLSYLHKDNQAAICRCSQP-LS 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 240 WWGWRNADDEYLVTSIAKAcalDPGTRAsggslstgtndaseacdtdfdssltacsgvestaapqkLLILDARSYTAAVA 319
Cdd:cd14532  80 GFSARCVEDEQLLQAIRKA---NPNSKF--------------------------------------MYVVDTRPKINAMA 118
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 320 NRAKGGGCECEEYYPNCEVLFMGMANIHAIRNSFQYLRAVCSQM-PDPSNWLSALESTKWLQHLSVMLKAAVLVANTVDr 398
Cdd:cd14532 119 NKAAGKGYENEDNYSNIKFQFFGIENIHVMRSSLQKLLEVCELKnPSMSAFLSGLESSGWLKHIKAVMDTSVFIAKAVS- 197
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 399 EGRPVLVHCSDGWDRTPQIVALAKILLDPYYRTLEGFQVLVESDWLDFGHKFGDRCGHQENaeDQNEQCPVFLQWLDSVH 478
Cdd:cd14532 198 EGASVLVHCSDGWDRTAQTCSLASLLLDPYYRTIKGFQVLIEKEWLSFGHKFTDRCGHLQG--DAKEVSPVFTQFLDCVW 275
                       330       340
                ....*....|....*....|.
gi 34784179 479 QLLKQFPCLFEFNEAFLV-LH 498
Cdd:cd14532 276 QLMQQFPRAFEFNERFLLtLH 296
PTP-MTM1-like cd14535
protein tyrosine phosphatase-like domain of myotubularin, and myotubularin related ...
215-497 6.07e-86

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: 275.10  E-value: 6.07e-86
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 215 RIPVVVYRHLRNGAAIARCSQPEISWWGWRNADDEYLVTSIakacaldpgtrasggslstgtndaseacdtdfdssltac 294
Cdd:cd14535   2 RIPVLSWIHPESQATITRCSQPLVGVSGKRSKDDEKYLQLI--------------------------------------- 42
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 295 sgVESTAAPQKLLILDARSYTAAVANRAKGGGCECEEYYPNCEVLFMGMANIHAIRNSFQYLRAVCSQMPDPSNWLSALE 374
Cdd:cd14535  43 --MDANAQSHKLFIMDARPSVNAVANKAKGGGYESEDAYQNAELVFLDIHNIHVMRESLRKLKDICFPNIDDSHWLSNLE 120
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 375 STKWLQHLSVMLKAAVLVANTVDREGRPVLVHCSDGWDRTPQIVALAKILLDPYYRTLEGFQVLVESDWLDFGHKFGDRC 454
Cdd:cd14535 121 STHWLEHIKLILAGAVRIADKVESGKTSVVVHCSDGWDRTAQLTSLAMLMLDPYYRTIRGFEVLIEKEWLSFGHKFAQRI 200
                       250       260       270       280
                ....*....|....*....|....*....|....*....|...
gi 34784179 455 GHQENAEDQNEQCPVFLQWLDSVHQLLKQFPCLFEFNEAFLVL 497
Cdd:cd14535 201 GHGDKNHSDADRSPVFLQFIDCVWQMTRQFPNAFEFNEHFLIT 243
PTP-MTMR8 cd14584
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
160-496 2.70e-85

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: 275.60  E-value: 2.70e-85
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 160 EAELARMGFDLQNvWRVSHINSNYKLCPSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLRNGAAIARCSQPeIS 239
Cdd:cd14584   8 KVDFQRMGIPNDY-WEITDANKNYEICSTYPPELVVPKSASKATVVGSSKFRSRGRFPVLSYLYKENNAAICRCSQP-LS 85
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 240 WWGWRNADDEYLVTSIAKAcalDPGTrasggslstgtndaseacdtdfdssltacsgvestaapQKLLILDARSYTAAVA 319
Cdd:cd14584  86 GFSARCVEDEQMLQAISKA---NPGS--------------------------------------PFMYVVDTRPKLNAMA 124
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 320 NRAKGGGCECEEYYPNCEVLFMGMANIHAIRNSFQYLRAVCS-QMPDPSNWLSALESTKWLQHLSVMLKAAVLVANTVDR 398
Cdd:cd14584 125 NRAAGKGYENEDNYSNIRFQFIGIENIHVMRSSLQKLLEVCEmKSPSMSDFLTGLENSGWLRHIKAVMDAGVFLAKAVKE 204
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 399 EGRPVLVHCSDGWDRTPQIVALAKILLDPYYRTLEGFQVLVESDWLDFGHKFGDRCGHQENaeDQNEQCPVFLQWLDSVH 478
Cdd:cd14584 205 EKASVLVHCSDGWDRTAQVCSLASLLLDPFYRTIKGLMVLIEKEWISMGHKFSQRCGHLDG--DPKEVSPVFTQFLECVW 282
                       330
                ....*....|....*...
gi 34784179 479 QLLKQFPCLFEFNEAFLV 496
Cdd:cd14584 283 QLMEQFPCAFEFNEHFLL 300
PTP-MTMR7 cd14583
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
160-496 1.82e-83

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: 270.29  E-value: 1.82e-83
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 160 EAELARMGFdLQNVWRVSHINSNYKLCPSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLRNGAAIARCSQPeIS 239
Cdd:cd14583   2 KAEYNRMGL-PNSLWQVSDVNRDYRVCDTYPTELYVPKSATAPIIVGSSKFRSRGRFPVLSYYCKDNNASICRSSQP-LS 79
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 240 WWGWRNADDEYLVTSIAKAcalDPGTrasggslstgtndaseacdtDFdssltacsgvestaapqkLLILDARSYTAAVA 319
Cdd:cd14583  80 GFSARCLEDEQMLQAIRKA---NPGS--------------------DF------------------MYVVDTRPKLNAMA 118
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 320 NRAKGGGCECEEYYPNCEVLFMGMANIHAIRNSFQYLRAVCS-QMPDPSNWLSALESTKWLQHLSVMLKAAVLVANTVDR 398
Cdd:cd14583 119 NRAAGKGYENEDNYSNIKFQFIGIENIHVMRNSLQKMLEVCElRSPSMGDFLWGLENSGWLKHIKAIMDAGIFIAKAVAE 198
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 399 EGRPVLVHCSDGWDRTPQIVALAKILLDPYYRTLEGFQVLVESDWLDFGHKFGDRCGHQENaeDQNEQCPVFLQWLDSVH 478
Cdd:cd14583 199 EGASVLVHCSDGWDRTAQVCSVASLLLDPYYRTIKGFMVLIEKDWVSFGHKFNHRYGHLDG--DPKEVSPVIDQFIECVW 276
                       330
                ....*....|....*...
gi 34784179 479 QLLKQFPCLFEFNEAFLV 496
Cdd:cd14583 277 QLMEQFPCAFEFNERFLI 294
PTP-MTMR6 cd14585
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
161-496 1.09e-82

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: 268.34  E-value: 1.09e-82
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 161 AELARMGFDlQNVWRVSHINSNYKLCPSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLRNGAAIARCSQPeISW 240
Cdd:cd14585   3 EEYKRMGVP-NDYWQLSDVNRDYKICDTYPRDLYVPITASKPIIVGSSKFRSKGRFPVLSYYHQEKKAAICRCSQP-LSG 80
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 241 WGWRNADDEYLVTSIAKAcalDPGTRasggslstgtndaseacdtdfdssltacsgvestaapqKLLILDARSYTAAVAN 320
Cdd:cd14585  81 FSARCLEDEHMLQAISKA---NPNNR--------------------------------------YMYVMDTRPKLNAMAN 119
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 321 RAKGGGCECEEYYPNCEVLFMGMANIHAIRNSFQYLRAVC-SQMPDPSNWLSALESTKWLQHLSVMLKAAVLVANTVDRE 399
Cdd:cd14585 120 RAAGKGYENEDNYSNIRFQFVGIENIHVMRSSLQKLLEVCgTKALSVNDFLSGLESSGWLRHIKAVLDAAVFLAKAVAVE 199
                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 400 GRPVLVHCSDGWDRTPQIVALAKILLDPYYRTLEGFQVLVESDWLDFGHKFGDRCGHQENaeDQNEQCPVFLQWLDSVHQ 479
Cdd:cd14585 200 GASVLVHCSDGWDRTAQVCSLGSLLLDPYYRTIKGFMVLIEKDWISFGHKFSDRCGQLDG--DPKEISPVFTQFLECVWQ 277
                       330
                ....*....|....*..
gi 34784179 480 LLKQFPCLFEFNEAFLV 496
Cdd:cd14585 278 LTEQFPRAFEFSEAFLL 294
PTP-MTMR2 cd14590
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
201-496 4.86e-82

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: 264.97  E-value: 4.86e-82
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 201 DKELENVASFRSWKRIPVVVYRHLRNGAAIARCSQPEISWWGWRNADDEYLVTSIakacaldpgtrasggslstgtndas 280
Cdd:cd14590   1 DEELKRVASFRSRGRIPVLSWIHPESQATITRCSQPMVGVSGKRSKEDEKYLQAI------------------------- 55
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 281 eacdtdfdssltacsgVESTAAPQKLLILDARSYTAAVANRAKGGGCECEEYYPNCEVLFMGMANIHAIRNSFQYLRAVC 360
Cdd:cd14590  56 ----------------MDSNAQSHKIFIFDARPSVNAVANKAKGGGYESEDAYQNAELVFLDIHNIHVMRESLRKLKEIV 119
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 361 SQMPDPSNWLSALESTKWLQHLSVMLKAAVLVANTVDREGRPVLVHCSDGWDRTPQIVALAKILLDPYYRTLEGFQVLVE 440
Cdd:cd14590 120 YPNIEESHWLSNLESTHWLEHIKLILAGALRIADKVESGKTSVVVHCSDGWDRTAQLTSLAMLMLDGYYRTIRGFEVLVE 199
                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 34784179 441 SDWLDFGHKFGDRCGHQENAEDQNEQCPVFLQWLDSVHQLLKQFPCLFEFNEAFLV 496
Cdd:cd14590 200 KEWLSFGHRFQLRVGHGDKNHADADRSPVFLQFIDCVWQMTRQFPTAFEFNEYFLI 255
PH-GRAM_MTMR4 cd13342
Myotubularian (MTM) related 4 protein (MTMR4) Pleckstrin Homology-Glucosyltransferases, ...
23-136 2.17e-78

Myotubularian (MTM) related 4 protein (MTMR4) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR4 is a member of the myotubularin dual specificity protein phosphatase gene family. MTMR4 binds to phosphoinositide lipids through its PH-GRAM domain, and can hydrolyze phosphatidylinositol(3)-phosphate and phosphatidylinositol(3,5)-biphosphate in vitro. The protein form heteromers with MTMR3. Both MTMR3 and MTMR4 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 lipid-binding FYVE domain which binds phosphotidylinositol-3-phosphate. 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: 270150  Cd Length: 114  Bit Score: 249.51  E-value: 2.17e-78
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179  23 LVKEEENLQVPFILLQGEGVEFLGRATDALIAISNYRLHIKFKDSVINVPLRMIDSVESRDMFQLHIACKDSKVVRCHFS 102
Cdd:cd13342   1 LVKEEESLQVPFPVLQGEGVEYLGHANDAVIAISNYRLHIKFKDSVINVPLRMMESVESRDMFQLHIICKDSKVVRCHFS 80
                        90       100       110
                ....*....|....*....|....*....|....
gi 34784179 103 TFKQCQEWLSRLSRATARPAKPEDLFAFAYHAWC 136
Cdd:cd13342  81 TFKQCQEWLKRLNRATARPAKPEDLFAFAYHAWC 114
PTP-MTM1 cd14591
protein tyrosine phosphatase-like domain of myotubularin phosphoinositide phosphatase 1; ...
215-496 8.30e-78

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: 253.41  E-value: 8.30e-78
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 215 RIPVVVYRHLRNGAAIARCSQPEISWWGWRNADDEYLVTSIAkacaldpgtrasggslstgtndaseacdtdfdssltac 294
Cdd:cd14591   2 RIPVLSWIHPENQAVIMRCSQPLVGMSGKRNKDDEKYLDIIR-------------------------------------- 43
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 295 sgvESTAAPQKLLILDARSYTAAVANRAKGGGCECEEYYPNCEVLFMGMANIHAIRNSFQYLRAVCSQMPDPSNWLSALE 374
Cdd:cd14591  44 ---EANGQTSKLTIYDARPSVNAVANKATGGGYEGDDAYQNAELVFLDIHNIHVMRESLKKLKDIVYPNVEESHWLSSLE 120
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 375 STKWLQHLSVMLKAAVLVANTVDREGRPVLVHCSDGWDRTPQIVALAKILLDPYYRTLEGFQVLVESDWLDFGHKFGDRC 454
Cdd:cd14591 121 STHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWDRTAQLTSLAMLMLDSYYRTIEGFEVLVQKEWISFGHKFASRI 200
                       250       260       270       280
                ....*....|....*....|....*....|....*....|..
gi 34784179 455 GHQENAEDQNEQCPVFLQWLDSVHQLLKQFPCLFEFNEAFLV 496
Cdd:cd14591 201 GHGDKNHADADRSPIFLQFIDCVWQMSKQFPTAFEFNEQFLI 242
PTP-MTMR1 cd14592
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
215-496 4.33e-69

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: 229.87  E-value: 4.33e-69
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 215 RIPVVVYRHLRNGAAIARCSQPEISWWGWRNADDEYLVTSIakacaldpgtrasggslstgtndaseacdtdfdssltac 294
Cdd:cd14592   2 RVPVLSWIHPESQATITRCSQPLVGPNDKRCKEDEKYLQTI--------------------------------------- 42
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 295 sgVESTAAPQKLLILDARSYTAAVANRAKGGGCECEEYYPNCEVLFMGMANIHAIRNSFQYLRAVCSQMPDPSNWLSALE 374
Cdd:cd14592  43 --MDANAQSHKLIIFDARQNSVADTNKTKGGGYESESAYPNAELVFLEIHNIHVMRESLRKLKEIVYPSIDEARWLSNVD 120
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 375 STKWLQHLSVMLKAAVLVANTVDREGRPVLVHCSDGWDRTPQIVALAKILLDPYYRTLEGFQVLVESDWLDFGHKFGDRC 454
Cdd:cd14592 121 GTHWLEYIRMLLAGAVRIADKIESGKTSVVVHCSDGWDRTAQLTSLAMLMLDSYYRTIKGFEVLIEKEWISFGHRFALRV 200
                       250       260       270       280
                ....*....|....*....|....*....|....*....|..
gi 34784179 455 GHQENAEDQNEQCPVFLQWLDSVHQLLKQFPCLFEFNEAFLV 496
Cdd:cd14592 201 GHGDDNHADADRSPIFLQFIDCVWQMTRQFPSAFEFNELFLI 242
PTP-MTM-like_fungal cd17666
protein tyrosine phosphatase-like domain of fungal myotubularins; Myotubularins are a unique ...
214-479 9.33e-69

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: 228.10  E-value: 9.33e-69
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 214 KRIPVVVYRHLRNGAAIARCSQPEISWWGWRNADDEYLVTSIakacaldpgtrasggslstgtndaseacdtdFDSSLTA 293
Cdd:cd17666   1 QRIPVLTYLHKANGCSITRSSQPLVGLKQNRSIQDEKLVSEI-------------------------------FNTSINE 49
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 294 CSGvestaAPQKLLILDARSYTAAVANRAKGGGCECEE--YYPNCEVLFMGMANIHAIRNSFQYLRAVC-----SQMPDP 366
Cdd:cd17666  50 IYI-----SPQKNLIVDARPTTNAMAQVALGAGTENMDnyKYKTAKKIYLGIDNIHVMRDSLNKVTEALkdgddSNPSYP 124
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 367 SNwLSALESTKWLQHLSVMLKAAVLVANTVDREGRPVLVHCSDGWDRTPQIVALAKILLDPYYRTLEGFQVLVESDWLDF 446
Cdd:cd17666 125 PL-INALKKSNWLKYLAIILQGADLIAKSIHFNHSHVLIHCSDGWDRTSQLSALAQLCLDPYYRTLEGFMVLVEKDWLSF 203
                       250       260       270
                ....*....|....*....|....*....|...
gi 34784179 447 GHKFGDRCGHQENAedqneqcPVFLQWLDSVHQ 479
Cdd:cd17666 204 GHRFAERSGHKETS-------PVFHQFLDCVYQ 229
PH-GRAM_MTMR3_MTMR4 cd13209
Myotubularian (MTM) related 3 and 4 proteins (MTMR3 and MTMR4) Pleckstrin ...
23-116 2.71e-59

Myotubularian (MTM) related 3 and 4 proteins (MTMR3 and MTMR4) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR3 is a member of the myotubularin dual specificity protein phosphatase gene family. MTMR3 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 also form heteromers with MTMR4. MTMR4, a member of the myotubularin dual specificity protein phosphatase gene family. MTMR4 binds to phosphoinositide lipids through its PH-GRAM domain, and can hydrolyze phosphatidylinositol(3)-phosphate and phosphatidylinositol(3,5)-biphosphate in vitro. The protein form heteromers with MTMR3. Both MTMR3 and MTMR4 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 lipid-binding FYVE domain which binds phosphotidylinositol-3-phosphate. 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: 275397  Cd Length: 94  Bit Score: 196.98  E-value: 2.71e-59
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179  23 LVKEEENLQVPFILLQGEGVEFLGRATDALIAISNYRLHIKFKDSVINVPLRMIDSVESRDMFQLHIACKDSKVVRCHFS 102
Cdd:cd13209   1 LVKEDENLQVPFPELHGEGTEYVGRAEDAVIAISNYRLHIKFKESVINVPLQLIESVECRDMFQLHITCKDCKVIRCQFS 80
                        90
                ....*....|....
gi 34784179 103 TFKQCQEWLSRLSR 116
Cdd:cd13209  81 TFEQCQEWLKRLNR 94
PTP-MTMR5-like cd14534
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
174-483 3.51e-54

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: 189.50  E-value: 3.51e-54
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 174 WRVSHINSNYKLCPSYPQKLLVPVWITDKELENVA-SFRSwKRIPVVVYRHLRNGAAIARCSQPEiswwgwrnaddeylV 252
Cdd:cd14534   1 FRISTANRDYSICRSYPALVVVPQSVSDESLRKVArCYRQ-GRFPVVTWRHPRTKALLLRSGGFH--------------G 65
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 253 TSIAkacaldpGTRASGGSLSTGTNDASeacdTDFDSSLTAcsgvESTAAPQKLLILDARSYTAAVANrakgggceceEY 332
Cdd:cd14534  66 KGVM-------GMLKSANTSTSSPTVSS----SETSSSLEQ----EKYLSALVLYVLGEKSQMKGVKA----------ES 120
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 333 YPNCEVLFMGMANIHAIRNSFQYLRAVC----SQMPDPSNWLSALESTKWLQHLSVMLKAAVLVANTVDREGRPVLVHCS 408
Cdd:cd14534 121 DPKCEFIPVEYPEVRQVKASFKKLLRACvpssAPTEPEQSFLKAVEDSEWLQQLQCLMQLSGAVVDLLDVQGSSVLLCLE 200
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 34784179 409 DGWDRTPQIVALAKILLDPYYRTLEGFQVLVESDWLDFGHKFGDRCGHQENAEDQNeQCPVFLQWLDSVHQLLKQ 483
Cdd:cd14534 201 DGWDVTTQVSSLSQLLLDPYYRTLEGFRVLVEKEWLAFGHRFSHRSNLTAASQSSG-FAPVFLQFLDAVHQIHRQ 274
PTP-MTMR9 cd14536
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
215-479 1.69e-49

protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related phosphoinositide phosphatase 9; Myotubularin related phosphoinositide phosphatase 9 (MTMR9) is enzymatically inactive and contains a C-terminal coiled-coil domain and an N-terminal PH-GRAM domain. Mutations have been associated with obesity and metabolic syndrome. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. MTMR9 is a pseudophosphatase that lacks the catalytic cysteine in its catalytic pocket. It forms complexes with catalytically active MTMR6, MTMR7 and MTMR8, and regulates their activities; the complexes display differential substrate preferences. The MTMR6/R9 complex serves to inhibit stress-induced apoptosis while the MTMR8/R9 complex inhibits autophagy.


Pssm-ID: 350384  Cd Length: 224  Bit Score: 174.45  E-value: 1.69e-49
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 215 RIPVVVYRHLRNGAAIARCSQPEISWWGWRNADDEYLVTSiakacALDPGTRAsggslstgtndaseacdtdfdssltac 294
Cdd:cd14536   2 RFPVLSYYHKKNGMVLMRSSQPLTGPNGKRCKEDEKLLNA-----VLGGGKRG--------------------------- 49
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 295 sgvestaapqklLILDARSYTAAVANRAKGGGCECEEYYPNCEVLFMGMANIHAIRNSFQYLRAVCSqmpDPS----NWL 370
Cdd:cd14536  50 ------------YIIDTRSKNVAQQARAKGGGFEPEAHYPQWRRIHKPIERYNVLQESLIKLVEACN---DQGhsmdKWL 114
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 371 SALESTKWLQHLSVMLKAAVLVANTVDREGRPVLVHCSDGWDRTPQIVALAKILLDPYYRTLEGFQVLVESDWLDFGHKF 450
Cdd:cd14536 115 SKLESSNWLSHVKEILTTACLVAQCIDREGASVLVHGSEGMDSTLQVTSLAQIILDPDCRTIRGFEALIEREWLQAGHPF 194
                       250       260       270
                ....*....|....*....|....*....|
gi 34784179 451 GDRCGHQENAEDQN-EQCPVFLQWLDSVHQ 479
Cdd:cd14536 195 QSRCAKSAYSNSKQkFESPVFLLFLDCVWQ 224
PH-GRAM_MTMR3 cd13341
Myotubularian (MTM) related 3 protein (MTMR3) Pleckstrin Homology-Glucosyltransferases, ...
23-115 2.60e-47

Myotubularian (MTM) related 3 protein (MTMR3) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR3 is a member of the myotubularin dual specificity protein phosphatase gene family. MTMR3 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 also form heteromers with MTMR4. Both MTMR3 and MTMR4 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 lipid-binding FYVE domain which binds phosphotidylinositol-3-phosphate. 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: 270149  Cd Length: 94  Bit Score: 163.25  E-value: 2.60e-47
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179  23 LVKEEENLQVPFILLQGEGVEFLGRATDALIAISNYRLHIKFKDSVINVPLRMIDSVESRDMFQLHIACKDSKVVRCHFS 102
Cdd:cd13341   1 LIREDENLQVPFQELHGESTEFVGRAEDAIIALSNYRLHIKFKESVVNVPLQLIESVECRDIFQLHLTCKDCKVIRCQFS 80
                        90
                ....*....|...
gi 34784179 103 TFKQCQEWLSRLS 115
Cdd:cd13341  81 TFEQCQEWLKRLN 93
PTP-MTMR13 cd14589
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
174-483 4.62e-40

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: 150.07  E-value: 4.62e-40
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 174 WRVSHINSNYKLCPSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLRNGAAIARCSqpeiswwGWRNADdeylVT 253
Cdd:cd14589   1 FRITAVNRMYSLCRSYPGLLVVPQSVQDSSLQKVARCYRHNRLPVVCWKNSKTKAVLLRSG-------GFHGKG----VV 69
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 254 SIAKAcaLDPGTRASGGSLSTGTNDASEACDTDFDSSLTACS-GVESTAAPQKLLILDARSYTAAVANRAKGGGCEceeY 332
Cdd:cd14589  70 GLFKS--QNPHSAAPASSESSSSIEQEKYLQALLNAISVHQKmNGNSTLLQSQLLKRQAALYIFGEKSQLRGFKLD---F 144
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 333 YPNCEVLFMGMANIHAIRNSFQYLRAVC--SQMP-DP-SNWLSALESTKWLQHLSVMLKAAVLVANTVDrEGRPVLVHCS 408
Cdd:cd14589 145 ALNCEFVPVEFHDIRQVKASFKKLMRACvpSTIPtDSeVTFLKALGESEWFLQLHRIMQLAVVISELLE-SGSSVMVCLE 223
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 34784179 409 DGWDRTPQIVALAKILLDPYYRTLEGFQVLVESDWLDFGHKFGDRCGHQENAEDQNeQCPVFLQWLDSVHQLLKQ 483
Cdd:cd14589 224 DGWDITTQVVSLVQLLSDPFYRTLEGFQMLVEKEWLSFGHKFSQRSNLTPNSQGSG-FAPIFLQFLDCVHQIHNQ 297
PTP-MTMR5 cd14588
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
174-483 7.52e-40

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: 149.35  E-value: 7.52e-40
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 174 WRVSHINSNYKLCPSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLRNGAAIARCSqpeiswwGWRNADdeylVT 253
Cdd:cd14588   1 FRISTVNRMYAVCRSYPGLLIVPQSIQDNTIQRISRCYRQNRFPVVCWRNSRTKAVLLRSG-------GLHGKG----VV 69
                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 254 SIAKAcaldPGTRASGGSLSTGTNDASEACDTDFDSSLTACSgveSTAAPQKLLILDARSYTAAVANRAKGGGCECEEYY 333
Cdd:cd14588  70 GLFKS----QNAPAAGQSQTDSTSLEQEKYLQAVINSMPRYA---DASGRNTLSGFRAALYIIGDKSQLKGVKQDPLQQW 142
                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 334 pncEVLFMGMANIHAIRNSFQYLRAVC----SQMPDPSNWLSALESTKWLQHLSVMLKAAVLVANTVDrEGRPVLVHCSD 409
Cdd:cd14588 143 ---EVVPIEVFDVRQVKASFKKLMKACvpscPSTDPSQTYLRTLEESEWLSQLHKLLQVSVLVVELLD-SGSSVLVSLED 218
                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 34784179 410 GWDRTPQIVALAKILLDPYYRTLEGFQVLVESDWLDFGHKFGDRcGHQENAEDQNEQCPVFLQWLDSVHQLLKQ 483
Cdd:cd14588 219 GWDITTQVVSLVQLLSDPYYRTIEGFRLLVEKEWLSFGHRFSHR-GAQTLASQSSGFTPVFLQFLDCVHQIHLQ 291
PTP-MTMR10-like cd14537
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
344-479 6.21e-32

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: 123.22  E-value: 6.21e-32
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 344 ANIHAirnSFQYLRAVCsqMPDP--------SNWLSALESTKWLQHLSVMLKAAVLVANTVDREGRPVLVHCSDGWDRTP 415
Cdd:cd14537  62 QDVQA---AYLKLRELC--TPDSseqfwvqdSKWYSLLENTKWLHYVSACLKKASEAAEALESRGRSVVLQESDGRDLSC 136
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 34784179 416 QIVALAKILLDPYYRTLEGFQVLVESDWLDFGHKFGDRCGHQENAEDQNEQCPVFLQWLDSVHQ 479
Cdd:cd14537 137 VVSSLVQLLLDPHFRTITGFQSLIQKEWVALGHPFCDRLGHVKPNKTESEESPVFLLFLDCVWQ 200
PTP-MTMR10 cd14593
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
343-479 2.05e-23

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: 98.81  E-value: 2.05e-23
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 343 MANIHAIRNSFQYLRAVCSQMP---DPSNWLSALESTKWLQHLSVMLKAAVLVANTVDREGRPVLVHCSDGWDRTPQIVA 419
Cdd:cd14593  58 LPNIQEIQAAFVKLKQLCVNEPfeeTEEKWLSSLESTRWLEYVRAFLKHSAELVYMLESKHVSVILQEEEGRDLSCVVAS 137
                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 420 LAKILLDPYYRTLEGFQVLVESDWLDFGHKFGDRCGHQENAEDQneQCPVFLQWLDSVHQ 479
Cdd:cd14593 138 LVQVMLDPYFRTITGFQSLIQKEWVMAGYRFLDRCNHLKKSSKK--ESPLFLLFLDCVWQ 195
PTP-MTMR12 cd14594
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
369-480 3.16e-21

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: 92.60  E-value: 3.16e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 369 WLSALESTKWLQHLSVMLKAAVLVANTVDREGRPVLVHCSDGWDRTPQIVALAKILLDPYYRTLEGFQVLVESDWLDFGH 448
Cdd:cd14594  94 WFSSLESSNWLEIIRQCLKKAVEVVECLEKQNTNVLLTEEEATDLCCVISSLVQIMMDPYCRTKSGFQSLIQKEWVMGGH 173
                        90       100       110
                ....*....|....*....|....*....|..
gi 34784179 449 KFGDRCGHQEnaEDQNEQCPVFLQWLDSVHQL 480
Cdd:cd14594 174 CFLDRCNHLR--QNDKEEVPVFLLFLDCVWQL 203
PTP-MTMR11 cd14595
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
349-480 1.23e-20

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: 90.66  E-value: 1.23e-20
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179 349 IRNSFQYLRAVCsqMPDPS------NWLSALESTKWLQHLSVMLKAAVLVANTVDREGRPVLVHCSDGWDRTPQIVALAK 422
Cdd:cd14595  62 IQLAYLKLRTLC--LPDISvsvsdeKWLSNLEGTRWLDHVRACLRKASEVSCLLAERHRSVILQESEDRDLNCLLSSLVQ 139
                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 34784179 423 ILLDPYYRTLEGFQVLVESDWLDFGHKFGDRCG-HQENAEdqnEQCPVFLQWLDSVHQL 480
Cdd:cd14595 140 LLSDPHARTISGFQSLVQKEWVVAGHPFLQRLNlTRESDK---EESPVFLLFLDCVWQL 195
PH-GRAM cd10570
Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins ...
27-114 2.11e-07

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: 49.69  E-value: 2.11e-07
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 34784179  27 EENLQVPF------ILLQGEGVEFLGraTDALIAISNYRLHikfkDSVINVPLRMIDSVESRDMFQ-----LHIACKDSK 95
Cdd:cd10570   1 IEKLGVRFccalrpRKLPLEGTLYLS--TYRLIFSSKADGD----ETKLVIPLVDITDVEKIAGASflpsgLIITCKDFR 74
                        90
                ....*....|....*....
gi 34784179  96 VVRCHFSTFKQCQEWLSRL 114
Cdd:cd10570  75 TIKFSFDSEDEAVKVIARV 93
PTPc_motif smart00404
Protein tyrosine phosphatase, catalytic domain motif;
402-433 7.99e-06

Protein tyrosine phosphatase, catalytic domain motif;


Pssm-ID: 214649 [Multi-domain]  Cd Length: 105  Bit Score: 45.43  E-value: 7.99e-06
                           10        20        30
                   ....*....|....*....|....*....|..
gi 34784179    402 PVLVHCSDGWDRTPQIVALAKILLDPYYRTLE 433
Cdd:smart00404  41 PVVVHCSAGVGRTGTFVAIDILLQQLEAEAGE 72
PTPc_DSPc smart00012
Protein tyrosine phosphatase, catalytic domain, undefined specificity; Protein tyrosine ...
402-433 7.99e-06

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: 45.43  E-value: 7.99e-06
                           10        20        30
                   ....*....|....*....|....*....|..
gi 34784179    402 PVLVHCSDGWDRTPQIVALAKILLDPYYRTLE 433
Cdd:smart00012  41 PVVVHCSAGVGRTGTFVAIDILLQQLEAEAGE 72
PTP_DSP_cys cd14494
cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This ...
366-425 3.16e-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: 3.16e-05
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 34784179 366 PSNWLSALESTKWLQHLSV-------MLKAAVLVANTVDREGRPVLVHCSDGWDRTPQIVALAKILL 425
Cdd:cd14494  15 PLSPLEADSRFLKQLGVTTivdltlaMVDRFLEVLDQAEKPGEPVLVHCKAGVGRTGTLVACYLVLL 81
PH-GRAM_MTM-like cd13223
Myotubularian 1 and related proteins Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase; ...
53-106 1.93e-03

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


Pssm-ID: 275407  Cd Length: 100  Bit Score: 38.37  E-value: 1.93e-03
                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 34784179  53 IAISNYRLHIKFKDS----VINVPLRMIDSVE--------SRDMFQLHIACKDSKVVRchFsTFKQ 106
Cdd:cd13223  20 LYITNYRLYFKSRDRepnfVLDVPLGVISRVEkvggatsrGENSYGLEIHCKDMRNLR--F-AHKQ 82
 
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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