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Conserved domains on  [gi|33112674|sp|Q9Z2C9|]
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RecName: Full=Myotubularin-related protein 7; AltName: Full=Inositol 1,3-bisphosphate phosphatase; AltName: Full=Phosphatidylinositol-3-phosphate phosphatase

Protein Classification

PH-GRAM_MTMR7 and PTP-MTMR7 domain-containing protein( domain architecture ID 12988794)

PH-GRAM_MTMR7 and PTP-MTMR7 domain-containing protein

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PTP-MTMR7 cd14583
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 132-433 0e+00

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: 672.44  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 132 LSEEYKRMGLPDNYWQLSDVNRDYRVCDSYPTELYVPRSATAHIIVGSSKFRSRRRFPALSYYCKDSHASICRSSQPLSG 211
Cdd:cd14583   1 LKAEYNRMGLPNSLWQVSDVNRDYRVCDTYPTELYVPKSATAPIIVGSSKFRSRGRFPVLSYYCKDNNASICRSSQPLSG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 212 FSARCLEDEQMLQAIRKANPGSDFIYVVDTRPKLNAMANRAAGKGYENEDNYSNIKFQFIGIENIHVMRNSLQKMLEVCE 291
Cdd:cd14583  81 FSARCLEDEQMLQAIRKANPGSDFMYVVDTRPKLNAMANRAAGKGYENEDNYSNIKFQFIGIENIHVMRNSLQKMLEVCE 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 292 LKSPSMSDFLWGLENSGWLRHIKAIMDAGIFIAKAVSEEGASVLVHCSDGWDRTAQVCSVASLLLDPYYRTLKGFMVLIE 371
Cdd:cd14583 161 LRSPSMGDFLWGLENSGWLKHIKAIMDAGIFIAKAVAEEGASVLVHCSDGWDRTAQVCSVASLLLDPYYRTIKGFMVLIE 240

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 33112674 372 KDWISFGHKFNHRYGNLDGDPKEISPVIDQFIECVWQLTEQFPCAFEFNERFLTHIQHHVYS 433
Cdd:cd14583 241 KDWVSFGHKFNHRYGHLDGDPKEVSPVIDQFIECVWQLMEQFPCAFEFNERFLIHIHHHIYS 302
PH-GRAM_MTMR7 cd13344
Myotubularian (MTM) related 7 protein (MTMR7) Pleckstrin Homology-Glucosyltransferases, ...
 1-103 2.89e-69

Myotubularian (MTM) related 7 protein (MTMR7) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR7 is a member of the myotubularin dual specificity protein phosphatase gene family. MTMR6 binds to phosphoinositide lipids through its PH-GRAM domain and can hydrolyze phosphatidylinositol(3)-phosphate and phosphatidylinositol(3,5)-biphosphate. MTMR7 interacts with MTMR6, MTMR8 and MTMR9. MTMR7 contains a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an active PTP domain, a SET-interaction domain, and a C-terminal coiled-coil region. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 6 of the 13 MTMRs (MTMRs 5, 9-13) contain naturally occurring substitutions of residues required for catalysis by PTP family enzymes. Although these proteins are predicted to be enzymatically inactive, they are thought to function as antagonists of endogenous phosphatase activity or interaction modules. Most MTMRs contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, a PTP domain (which may be active or inactive), a SET-interaction domain, and a C-terminal coiled-coil region. In addition some members contain DENN domain N-terminal to the PH-GRAM domain and FYVE, PDZ, and PH domains C-terminal to the coiled-coil region. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. The PH domain family possesses multiple functions including the ability to bind phosphoinositides via its beta1/beta2, beta3/beta4, and beta6/beta7 connecting loops and to other proteins. However, no phosphoinositide binding sites have been found for the MTMRs to date.


:

Pssm-ID: 270152  Cd Length: 103  Bit Score: 220.56  E-value: 2.89e-69
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674   1 MEHIRTPKVENVRLVDRVSCKKAALGTLYLTATHVIFVENAPDTRKETWILHSQISTIEKQATTATGCPLLIRCKNFQIV 80
Cdd:cd13344   1 MEHIRMPKVENVRLVDRISSKKAALGTLYLTATHVIFVENSSDTRKETWILHSQISSIEKQATTATGCPLLIRCKNFQVI 80

                        90       100
                ....*....|....*....|...
gi 33112674  81 QLVIPQERDCHDVYISLIRLARP 103
Cdd:cd13344  81 QLIIPQERDCHDVYISLIRLARP 103
 
Name Accession Description Interval E-value
PTP-MTMR7 cd14583
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 132-433 0e+00

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: 672.44  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 132 LSEEYKRMGLPDNYWQLSDVNRDYRVCDSYPTELYVPRSATAHIIVGSSKFRSRRRFPALSYYCKDSHASICRSSQPLSG 211
Cdd:cd14583   1 LKAEYNRMGLPNSLWQVSDVNRDYRVCDTYPTELYVPKSATAPIIVGSSKFRSRGRFPVLSYYCKDNNASICRSSQPLSG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 212 FSARCLEDEQMLQAIRKANPGSDFIYVVDTRPKLNAMANRAAGKGYENEDNYSNIKFQFIGIENIHVMRNSLQKMLEVCE 291
Cdd:cd14583  81 FSARCLEDEQMLQAIRKANPGSDFMYVVDTRPKLNAMANRAAGKGYENEDNYSNIKFQFIGIENIHVMRNSLQKMLEVCE 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 292 LKSPSMSDFLWGLENSGWLRHIKAIMDAGIFIAKAVSEEGASVLVHCSDGWDRTAQVCSVASLLLDPYYRTLKGFMVLIE 371
Cdd:cd14583 161 LRSPSMGDFLWGLENSGWLKHIKAIMDAGIFIAKAVAEEGASVLVHCSDGWDRTAQVCSVASLLLDPYYRTIKGFMVLIE 240

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 33112674 372 KDWISFGHKFNHRYGNLDGDPKEISPVIDQFIECVWQLTEQFPCAFEFNERFLTHIQHHVYS 433
Cdd:cd14583 241 KDWVSFGHKFNHRYGHLDGDPKEVSPVIDQFIECVWQLMEQFPCAFEFNERFLIHIHHHIYS 302
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
 124-448 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: 611.79  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674   124 EQGWLLVDLSEEYKRMGLP-DNYWQLSDVNRDYRVCDSYPTELYVPRSATAHIIVGSSKFRSRRRFPALSYYCKDSHASI 202
Cdd:pfam06602   2 ENGWDLYDPEAEFARQGLPsKDEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHKENGAVI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674   203 CRSSQPLSGF-SARCLEDEQMLQAIRKAN--PGSDFIYVVDTRPKLNAMANRAAGKGYENEDNYSNIKFQFIGIENIHVM 279
Cdd:pfam06602  82 TRSSQPLVGLnGKRSIEDEKLLQAIFKSSnpYSAKKLYIVDARPKLNAMANRAKGGGYENEDNYPNCKKIFLGIENIHVM 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674   280 RNSLQKMLEVCELKSPSMSDFLWGLENSGWLRHIKAIMDAGIFIAKAVSEEGASVLVHCSDGWDRTAQVCSVASLLLDPY 359
Cdd:pfam06602 162 RDSLNKLVEACNDRSPSMDKWLSRLESSGWLKHIKAILDGACLIAQAVDLEGSSVLVHCSDGWDRTAQLTSLAQLLLDPY 241

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674   360 YRTLKGFMVLIEKDWISFGHKFNHRYGNLDG--DPKEISPVIDQFIECVWQLTEQFPCAFEFNERFLTHIQHHVYSCQFG 437
Cdd:pfam06602 242 YRTIEGFQVLIEKEWLSFGHKFADRCGHLAGftDSKERSPVFLQFLDCVWQLLRQFPCAFEFNERFLIRLLYHLYSCQFG 321

                         330
                  ....*....|.
gi 33112674   438 NFLCNSQKERR 448
Cdd:pfam06602 322 TFLCNSEKERV 332
PH-GRAM_MTMR7 cd13344
Myotubularian (MTM) related 7 protein (MTMR7) Pleckstrin Homology-Glucosyltransferases, ...
 1-103 2.89e-69

Myotubularian (MTM) related 7 protein (MTMR7) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR7 is a member of the myotubularin dual specificity protein phosphatase gene family. MTMR6 binds to phosphoinositide lipids through its PH-GRAM domain and can hydrolyze phosphatidylinositol(3)-phosphate and phosphatidylinositol(3,5)-biphosphate. MTMR7 interacts with MTMR6, MTMR8 and MTMR9. MTMR7 contains a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an active PTP domain, a SET-interaction domain, and a C-terminal coiled-coil region. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 6 of the 13 MTMRs (MTMRs 5, 9-13) contain naturally occurring substitutions of residues required for catalysis by PTP family enzymes. Although these proteins are predicted to be enzymatically inactive, they are thought to function as antagonists of endogenous phosphatase activity or interaction modules. Most MTMRs contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, a PTP domain (which may be active or inactive), a SET-interaction domain, and a C-terminal coiled-coil region. In addition some members contain DENN domain N-terminal to the PH-GRAM domain and FYVE, PDZ, and PH domains C-terminal to the coiled-coil region. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. The PH domain family possesses multiple functions including the ability to bind phosphoinositides via its beta1/beta2, beta3/beta4, and beta6/beta7 connecting loops and to other proteins. However, no phosphoinositide binding sites have been found for the MTMRs to date.


Pssm-ID: 270152  Cd Length: 103  Bit Score: 220.56  E-value: 2.89e-69
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674   1 MEHIRTPKVENVRLVDRVSCKKAALGTLYLTATHVIFVENAPDTRKETWILHSQISTIEKQATTATGCPLLIRCKNFQIV 80
Cdd:cd13344   1 MEHIRMPKVENVRLVDRISSKKAALGTLYLTATHVIFVENSSDTRKETWILHSQISSIEKQATTATGCPLLIRCKNFQVI 80

                        90       100
                ....*....|....*....|...
gi 33112674  81 QLVIPQERDCHDVYISLIRLARP 103
Cdd:cd13344  81 QLIIPQERDCHDVYISLIRLARP 103
PTPc_motif smart00404
Protein tyrosine phosphatase, catalytic domain motif;
328-364 4.76e-06

Protein tyrosine phosphatase, catalytic domain motif;


Pssm-ID: 214649 [Multi-domain]  Cd Length: 105  Bit Score: 45.81  E-value: 4.76e-06
                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 33112674    328 SEEGASVLVHCSDGWDRTAQVCSVASLLLDPYYRTLK 364
Cdd:smart00404  36 SESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEAGE 72
 
Name Accession Description Interval E-value
PTP-MTMR7 cd14583
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 132-433 0e+00

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: 672.44  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 132 LSEEYKRMGLPDNYWQLSDVNRDYRVCDSYPTELYVPRSATAHIIVGSSKFRSRRRFPALSYYCKDSHASICRSSQPLSG 211
Cdd:cd14583   1 LKAEYNRMGLPNSLWQVSDVNRDYRVCDTYPTELYVPKSATAPIIVGSSKFRSRGRFPVLSYYCKDNNASICRSSQPLSG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 212 FSARCLEDEQMLQAIRKANPGSDFIYVVDTRPKLNAMANRAAGKGYENEDNYSNIKFQFIGIENIHVMRNSLQKMLEVCE 291
Cdd:cd14583  81 FSARCLEDEQMLQAIRKANPGSDFMYVVDTRPKLNAMANRAAGKGYENEDNYSNIKFQFIGIENIHVMRNSLQKMLEVCE 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 292 LKSPSMSDFLWGLENSGWLRHIKAIMDAGIFIAKAVSEEGASVLVHCSDGWDRTAQVCSVASLLLDPYYRTLKGFMVLIE 371
Cdd:cd14583 161 LRSPSMGDFLWGLENSGWLKHIKAIMDAGIFIAKAVAEEGASVLVHCSDGWDRTAQVCSVASLLLDPYYRTIKGFMVLIE 240

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 33112674 372 KDWISFGHKFNHRYGNLDGDPKEISPVIDQFIECVWQLTEQFPCAFEFNERFLTHIQHHVYS 433
Cdd:cd14583 241 KDWVSFGHKFNHRYGHLDGDPKEVSPVIDQFIECVWQLMEQFPCAFEFNERFLIHIHHHIYS 302
PTP-MTMR6-like cd14532
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases ...
 132-433 0e+00

protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases 6, 7, and 8; This subgroup of enzymatically active phosphatase domains of myotubularins consists of MTMR6, MTMR7 and MTMR8, and related domains. Beside the phosphatase domain, they contain a C-terminal coiled-coil domain and an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively. MTMR6, MTMR7 and MTMR8 form complexes with catalytically inactive MTMR9, and display differential substrate preferences. In cells, the MTMR6/R9 complex significantly increases the cellular levels of PtdIns(5)P, the product of PI(3,5)P(2) dephosphorylation, whereas the MTMR8/R9 complex reduces cellular PtdIns(3)P levels. The MTMR6/R9 complex serves to inhibit stress-induced apoptosis while the MTMR8/R9 complex inhibits autophagy.


Pssm-ID: 350380 [Multi-domain]  Cd Length: 301  Bit Score: 642.47  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 132 LSEEYKRMGLPDNYWQLSDVNRDYRVCDSYPTELYVPRSATAHIIVGSSKFRSRRRFPALSYYCKDSHASICRSSQPLSG 211
Cdd:cd14532   1 LESEYTRMGVPNDNWTLSDINKDYELCDTYPRELFVPTSASTPVLVGSSKFRSKGRLPVLSYLHKDNQAAICRCSQPLSG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 212 FSARCLEDEQMLQAIRKANPGSDFIYVVDTRPKLNAMANRAAGKGYENEDNYSNIKFQFIGIENIHVMRNSLQKMLEVCE 291
Cdd:cd14532  81 FSARCVEDEQLLQAIRKANPNSKFMYVVDTRPKINAMANKAAGKGYENEDNYSNIKFQFFGIENIHVMRSSLQKLLEVCE 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 292 LKSPSMSDFLWGLENSGWLRHIKAIMDAGIFIAKAVSeEGASVLVHCSDGWDRTAQVCSVASLLLDPYYRTLKGFMVLIE 371
Cdd:cd14532 161 LKNPSMSAFLSGLESSGWLKHIKAVMDTSVFIAKAVS-EGASVLVHCSDGWDRTAQTCSLASLLLDPYYRTIKGFQVLIE 239

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 33112674 372 KDWISFGHKFNHRYGNLDGDPKEISPVIDQFIECVWQLTEQFPCAFEFNERFLTHIQHHVYS 433
Cdd:cd14532 240 KEWLSFGHKFTDRCGHLQGDAKEVSPVFTQFLDCVWQLMQQFPRAFEFNERFLLTLHDHVYS 301
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
 124-448 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: 611.79  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674   124 EQGWLLVDLSEEYKRMGLP-DNYWQLSDVNRDYRVCDSYPTELYVPRSATAHIIVGSSKFRSRRRFPALSYYCKDSHASI 202
Cdd:pfam06602   2 ENGWDLYDPEAEFARQGLPsKDEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHKENGAVI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674   203 CRSSQPLSGF-SARCLEDEQMLQAIRKAN--PGSDFIYVVDTRPKLNAMANRAAGKGYENEDNYSNIKFQFIGIENIHVM 279
Cdd:pfam06602  82 TRSSQPLVGLnGKRSIEDEKLLQAIFKSSnpYSAKKLYIVDARPKLNAMANRAKGGGYENEDNYPNCKKIFLGIENIHVM 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674   280 RNSLQKMLEVCELKSPSMSDFLWGLENSGWLRHIKAIMDAGIFIAKAVSEEGASVLVHCSDGWDRTAQVCSVASLLLDPY 359
Cdd:pfam06602 162 RDSLNKLVEACNDRSPSMDKWLSRLESSGWLKHIKAILDGACLIAQAVDLEGSSVLVHCSDGWDRTAQLTSLAQLLLDPY 241

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674   360 YRTLKGFMVLIEKDWISFGHKFNHRYGNLDG--DPKEISPVIDQFIECVWQLTEQFPCAFEFNERFLTHIQHHVYSCQFG 437
Cdd:pfam06602 242 YRTIEGFQVLIEKEWLSFGHKFADRCGHLAGftDSKERSPVFLQFLDCVWQLLRQFPCAFEFNERFLIRLLYHLYSCQFG 321

                         330
                  ....*....|.
gi 33112674   438 NFLCNSQKERR 448
Cdd:pfam06602 322 TFLCNSEKERV 332
PTP-MTMR8 cd14584
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 126-433 0e+00

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: 598.01  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 126 GWLLVDLSEEYKRMGLPDNYWQLSDVNRDYRVCDSYPTELYVPRSATAHIIVGSSKFRSRRRFPALSYYCKDSHASICRS 205
Cdd:cd14584   1 GWKLIDLKVDFQRMGIPNDYWEITDANKNYEICSTYPPELVVPKSASKATVVGSSKFRSRGRFPVLSYLYKENNAAICRC 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 206 SQPLSGFSARCLEDEQMLQAIRKANPGSDFIYVVDTRPKLNAMANRAAGKGYENEDNYSNIKFQFIGIENIHVMRNSLQK 285
Cdd:cd14584  81 SQPLSGFSARCVEDEQMLQAISKANPGSPFMYVVDTRPKLNAMANRAAGKGYENEDNYSNIRFQFIGIENIHVMRSSLQK 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 286 MLEVCELKSPSMSDFLWGLENSGWLRHIKAIMDAGIFIAKAVSEEGASVLVHCSDGWDRTAQVCSVASLLLDPYYRTLKG 365
Cdd:cd14584 161 LLEVCEMKSPSMSDFLTGLENSGWLRHIKAVMDAGVFLAKAVKEEKASVLVHCSDGWDRTAQVCSLASLLLDPFYRTIKG 240

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 33112674 366 FMVLIEKDWISFGHKFNHRYGNLDGDPKEISPVIDQFIECVWQLTEQFPCAFEFNERFLTHIQHHVYS 433
Cdd:cd14584 241 LMVLIEKEWISMGHKFSQRCGHLDGDPKEVSPVFTQFLECVWQLMEQFPCAFEFNEHFLLEIHDHVFS 308
PTP-MTMR6 cd14585
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 132-433 0e+00

protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase 6; Myotubularin related phosphoinositide phosphatase 6 is enzymatically active and contains a C-terminal coiled-coil domain and an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. They dephosphorylate the D-3 position of phosphatidylinositol 3-phosphate [PI(3)P] and phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2], generating phosphatidylinositol and phosphatidylinositol 5-phosphate [PI(5)P], respectively. MTMR6 forms a complex with catalytically inactive MTMR9 and preferentially dephosphorylates PtdIns(3,5)P(2); the MTMR6/R9 complex serves to inhibit stress-induced apoptosis.


Pssm-ID: 350433 [Multi-domain]  Cd Length: 302  Bit Score: 568.41  E-value: 0e+00
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 132 LSEEYKRMGLPDNYWQLSDVNRDYRVCDSYPTELYVPRSATAHIIVGSSKFRSRRRFPALSYYCKDSHASICRSSQPLSG 211
Cdd:cd14585   1 LAEEYKRMGVPNDYWQLSDVNRDYKICDTYPRDLYVPITASKPIIVGSSKFRSKGRFPVLSYYHQEKKAAICRCSQPLSG 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 212 FSARCLEDEQMLQAIRKANPGSDFIYVVDTRPKLNAMANRAAGKGYENEDNYSNIKFQFIGIENIHVMRNSLQKMLEVCE 291
Cdd:cd14585  81 FSARCLEDEHMLQAISKANPNNRYMYVMDTRPKLNAMANRAAGKGYENEDNYSNIRFQFVGIENIHVMRSSLQKLLEVCG 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 292 LKSPSMSDFLWGLENSGWLRHIKAIMDAGIFIAKAVSEEGASVLVHCSDGWDRTAQVCSVASLLLDPYYRTLKGFMVLIE 371
Cdd:cd14585 161 TKALSVNDFLSGLESSGWLRHIKAVLDAAVFLAKAVAVEGASVLVHCSDGWDRTAQVCSLGSLLLDPYYRTIKGFMVLIE 240

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 33112674 372 KDWISFGHKFNHRYGNLDGDPKEISPVIDQFIECVWQLTEQFPCAFEFNERFLTHIQHHVYS 433
Cdd:cd14585 241 KDWISFGHKFSDRCGQLDGDPKEISPVFTQFLECVWQLTEQFPRAFEFSEAFLLQIHEHIHS 302
PTP-MTM-like cd14507
protein tyrosine phosphatase-like domain of myotubularins; Myotubularins are a unique subgroup ...
 186-408 3.79e-124

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: 367.26  E-value: 3.79e-124
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 186 RRFPALSYYCKDSHASICRSSQPLSGF-SARCLEDEQMLQAIRKANPGSDFIYVVDTRPKLNAMANRAAGKGYENEDNYS 264
Cdd:cd14507   1 GRIPVLSWRHPRNGAVICRSSQPLVGLtGSRSKEDEKLLNAIRKASPSSKKLYIVDARPKLNAVANRAKGGGYENTEYYP 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 265 NIKFQFIGIENIHVMRNSLQKMLEVCELKSPSMSDFLWGLENSGWLRHIKAIMDAGIFIAKAVSEEGASVLVHCSDGWDR 344
Cdd:cd14507  81 NCELEFLNIENIHAMRDSLNKLRDACLSPNDEESNWLSALESSGWLEHIRLILKGAVRVADLLEKEGTSVLVHCSDGWDR 160

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 33112674 345 TAQVCSVASLLLDPYYRTLKGFMVLIEKDWISFGHKFNHRYGNLD--GDPKEISPVIDQFIECVWQ 408
Cdd:cd14507 161 TSQLTSLAQLLLDPYYRTIEGFQVLIEKEWLSFGHKFADRCGHGDknSSDEERSPIFLQFLDCVWQ 226
PTP-MTM1-like cd14535
protein tyrosine phosphatase-like domain of myotubularin, and myotubularin related ...
 187-432 6.26e-101

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: 308.22  E-value: 6.26e-101
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 187 RFPALSYYCKDSHASICRSSQPLSGFSA-RCLEDEQMLQAIRKANPGSDFIYVVDTRPKLNAMANRAAGKGYENEDNYSN 265
Cdd:cd14535   2 RIPVLSWIHPESQATITRCSQPLVGVSGkRSKDDEKYLQLIMDANAQSHKLFIMDARPSVNAVANKAKGGGYESEDAYQN 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 266 IKFQFIGIENIHVMRNSLQKMLEVCelkSPSMSDFLW--GLENSGWLRHIKAIMDAGIFIAKAVSEEGASVLVHCSDGWD 343
Cdd:cd14535  82 AELVFLDIHNIHVMRESLRKLKDIC---FPNIDDSHWlsNLESTHWLEHIKLILAGAVRIADKVESGKTSVVVHCSDGWD 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 344 RTAQVCSVASLLLDPYYRTLKGFMVLIEKDWISFGHKFNHRYGNldGDPK----EISPVIDQFIECVWQLTEQFPCAFEF 419
Cdd:cd14535 159 RTAQLTSLAMLMLDPYYRTIRGFEVLIEKEWLSFGHKFAQRIGH--GDKNhsdaDRSPVFLQFIDCVWQMTRQFPNAFEF 236

                       250
                ....*....|...
gi 33112674 420 NERFLTHIQHHVY 432
Cdd:cd14535 237 NEHFLITILDHLY 249
PTP-MTMR2 cd14590
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 180-432 2.93e-93

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: 289.24  E-value: 2.93e-93
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 180 SKFRSRRRFPALSYYCKDSHASICRSSQPLSGFSA-RCLEDEQMLQAIRKANPGSDFIYVVDTRPKLNAMANRAAGKGYE 258
Cdd:cd14590   8 ASFRSRGRIPVLSWIHPESQATITRCSQPMVGVSGkRSKEDEKYLQAIMDSNAQSHKIFIFDARPSVNAVANKAKGGGYE 87

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 259 NEDNYSNIKFQFIGIENIHVMRNSLQKMLEVCelkSPSMSDFLW--GLENSGWLRHIKAIMDAGIFIAKAVSEEGASVLV 336
Cdd:cd14590  88 SEDAYQNAELVFLDIHNIHVMRESLRKLKEIV---YPNIEESHWlsNLESTHWLEHIKLILAGALRIADKVESGKTSVVV 164

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 337 HCSDGWDRTAQVCSVASLLLDPYYRTLKGFMVLIEKDWISFGHKFNHRYGNLDGDPKEI--SPVIDQFIECVWQLTEQFP 414
Cdd:cd14590 165 HCSDGWDRTAQLTSLAMLMLDGYYRTIRGFEVLVEKEWLSFGHRFQLRVGHGDKNHADAdrSPVFLQFIDCVWQMTRQFP 244

                       250
                ....*....|....*...
gi 33112674 415 CAFEFNERFLTHIQHHVY 432
Cdd:cd14590 245 TAFEFNEYFLITILDHLY 262
PTP-MTM1 cd14591
protein tyrosine phosphatase-like domain of myotubularin phosphoinositide phosphatase 1; ...
 187-432 1.16e-88

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: 276.52  E-value: 1.16e-88
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 187 RFPALSYYCKDSHASICRSSQPLSGFSA-RCLEDEQMLQAIRKANPGSDFIYVVDTRPKLNAMANRAAGKGYENEDNYSN 265
Cdd:cd14591   2 RIPVLSWIHPENQAVIMRCSQPLVGMSGkRNKDDEKYLDIIREANGQTSKLTIYDARPSVNAVANKATGGGYEGDDAYQN 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 266 IKFQFIGIENIHVMRNSLQKMLEVCelkSPSMSDFLW--GLENSGWLRHIKAIMDAGIFIAKAVSEEGASVLVHCSDGWD 343
Cdd:cd14591  82 AELVFLDIHNIHVMRESLKKLKDIV---YPNVEESHWlsSLESTHWLEHIKLVLTGAIQVADKVSSGKSSVLVHCSDGWD 158

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 344 RTAQVCSVASLLLDPYYRTLKGFMVLIEKDWISFGHKFNHRYGNLDGDPKEI--SPVIDQFIECVWQLTEQFPCAFEFNE 421
Cdd:cd14591 159 RTAQLTSLAMLMLDSYYRTIEGFEVLVQKEWISFGHKFASRIGHGDKNHADAdrSPIFLQFIDCVWQMSKQFPTAFEFNE 238

                       250
                ....*....|.
gi 33112674 422 RFLTHIQHHVY 432
Cdd:cd14591 239 QFLITILDHLY 249
PTP-MTM-like_fungal cd17666
protein tyrosine phosphatase-like domain of fungal myotubularins; Myotubularins are a unique ...
 187-408 2.55e-83

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: 261.99  E-value: 2.55e-83
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 187 RFPALSYYCKDSHASICRSSQPLSGF-SARCLEDEQMLQAI------RKANPGSDFIyVVDTRPKLNAMANRAAGKGYEN 259
Cdd:cd17666   2 RIPVLTYLHKANGCSITRSSQPLVGLkQNRSIQDEKLVSEIfntsinEIYISPQKNL-IVDARPTTNAMAQVALGAGTEN 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 260 EDNYSN--IKFQFIGIENIHVMRNSLQKMLEV------CELKSPSMSDflwGLENSGWLRHIKAIMDAGIFIAKAVSEEG 331
Cdd:cd17666  81 MDNYKYktAKKIYLGIDNIHVMRDSLNKVTEAlkdgddSNPSYPPLIN---ALKKSNWLKYLAIILQGADLIAKSIHFNH 157

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 33112674 332 ASVLVHCSDGWDRTAQVCSVASLLLDPYYRTLKGFMVLIEKDWISFGHKFNHRYGNldgdpKEISPVIDQFIECVWQ 408
Cdd:cd17666 158 SHVLIHCSDGWDRTSQLSALAQLCLDPYYRTLEGFMVLVEKDWLSFGHRFAERSGH-----KETSPVFHQFLDCVYQ 229
PTP-MTMR1 cd14592
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 186-432 9.66e-81

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: 256.06  E-value: 9.66e-81
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 186 RRFPALSYYCKDSHASICRSSQPLSGFS-ARCLEDEQMLQAIRKANPGSDFIYVVDTRPKLNAMANRAAGKGYENEDNYS 264
Cdd:cd14592   1 GRVPVLSWIHPESQATITRCSQPLVGPNdKRCKEDEKYLQTIMDANAQSHKLIIFDARQNSVADTNKTKGGGYESESAYP 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 265 NIKFQFIGIENIHVMRNSLQKMLEVCelkSPSMSDFLW--GLENSGWLRHIKAIMDAGIFIAKAVSEEGASVLVHCSDGW 342
Cdd:cd14592  81 NAELVFLEIHNIHVMRESLRKLKEIV---YPSIDEARWlsNVDGTHWLEYIRMLLAGAVRIADKIESGKTSVVVHCSDGW 157

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 343 DRTAQVCSVASLLLDPYYRTLKGFMVLIEKDWISFGHKFNHRYGNLDGD--PKEISPVIDQFIECVWQLTEQFPCAFEFN 420
Cdd:cd14592 158 DRTAQLTSLAMLMLDSYYRTIKGFEVLIEKEWISFGHRFALRVGHGDDNhaDADRSPIFLQFIDCVWQMTRQFPSAFEFN 237

                       250
                ....*....|..
gi 33112674 421 ERFLTHIQHHVY 432
Cdd:cd14592 238 ELFLITILDHLY 249
PTP-MTMR4 cd14587
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 144-408 1.91e-72

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: 236.47  E-value: 1.91e-72
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 144 NYWQLSDVNRDYRVCDSYPTELYVPRSATAHIIVGSSKFRSRRRFPALSYYCKDSHASICRSSQP-LSGFSARCLEDEQM 222
Cdd:cd14587   1 NVWRVSEINSNYKLCSSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLRNGAVIARCSQPeISWWGWRNADDEYL 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 223 LQAIRKA---NPG--------------------SDF------------------IYVVDTRPKLNAMANRAAGKGYENED 261
Cdd:cd14587  81 VTSIAKAcalDPGtrapggspskgnsdgsdasdTDFdssltacsavesgaapqkLLILDARSYTAAVANRAKGGGCECEE 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 262 NYSNIKFQFIGIENIHVMRNSLQKMLEVCElKSPSMSDFLWGLENSGWLRHIKAIMDAGIFIAKAVSEEGASVLVHCSDG 341
Cdd:cd14587 161 YYPNCEVMFMGMANIHSIRNSFQYLRAVCS-QMPDPGNWLSALESTKWLQHLSVMLKAAVLVASAVDREGRPVLVHCSDG 239

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 33112674 342 WDRTAQVCSVASLLLDPYYRTLKGFMVLIEKDWISFGHKFNHRYGNLDG--DPKEISPVIDQFIECVWQ 408
Cdd:cd14587 240 WDRTPQIVALAKILLDPYYRTIEGFQVLVETDWLDFGHKFGDRCGHQENveDQNEQCPVFLQWLDCVHQ 308
PH-GRAM_MTMR7 cd13344
Myotubularian (MTM) related 7 protein (MTMR7) Pleckstrin Homology-Glucosyltransferases, ...
 1-103 2.89e-69

Myotubularian (MTM) related 7 protein (MTMR7) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR7 is a member of the myotubularin dual specificity protein phosphatase gene family. MTMR6 binds to phosphoinositide lipids through its PH-GRAM domain and can hydrolyze phosphatidylinositol(3)-phosphate and phosphatidylinositol(3,5)-biphosphate. MTMR7 interacts with MTMR6, MTMR8 and MTMR9. MTMR7 contains a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an active PTP domain, a SET-interaction domain, and a C-terminal coiled-coil region. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 6 of the 13 MTMRs (MTMRs 5, 9-13) contain naturally occurring substitutions of residues required for catalysis by PTP family enzymes. Although these proteins are predicted to be enzymatically inactive, they are thought to function as antagonists of endogenous phosphatase activity or interaction modules. Most MTMRs contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, a PTP domain (which may be active or inactive), a SET-interaction domain, and a C-terminal coiled-coil region. In addition some members contain DENN domain N-terminal to the PH-GRAM domain and FYVE, PDZ, and PH domains C-terminal to the coiled-coil region. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. The PH domain family possesses multiple functions including the ability to bind phosphoinositides via its beta1/beta2, beta3/beta4, and beta6/beta7 connecting loops and to other proteins. However, no phosphoinositide binding sites have been found for the MTMRs to date.


Pssm-ID: 270152  Cd Length: 103  Bit Score: 220.56  E-value: 2.89e-69
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674   1 MEHIRTPKVENVRLVDRVSCKKAALGTLYLTATHVIFVENAPDTRKETWILHSQISTIEKQATTATGCPLLIRCKNFQIV 80
Cdd:cd13344   1 MEHIRMPKVENVRLVDRISSKKAALGTLYLTATHVIFVENSSDTRKETWILHSQISSIEKQATTATGCPLLIRCKNFQVI 80

                        90       100
                ....*....|....*....|...
gi 33112674  81 QLVIPQERDCHDVYISLIRLARP 103
Cdd:cd13344  81 QLIIPQERDCHDVYISLIRLARP 103
PTP-MTMR3-like cd14533
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases ...
 186-408 3.93e-66

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: 216.89  E-value: 3.93e-66
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 186 RRFPALSYYCKDSHASICRSSQPLSGF-SARCLEDEQMLQAIRKANPGSD---FIYVVDTRPKLNAMANRAAGKGYENED 261
Cdd:cd14533   2 KRIPSVVWRHQRNGAVIARCSQPEVGWlGWRNAEDENLLQAIAEACASNAspkKLLIVDARSYAAAVANRAKGGGCECPE 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 262 NYSNIKFQFIGIENIHVMRNSLQKMLEVCElKSPSMSDFLWGLENSGWLRHIKAIMDAGIFIAKAVSEEGASVLVHCSDG 341
Cdd:cd14533  82 YYPNCEVVFMNLANIHAIRKSFHSLRALCS-SAPDQPNWLSNLESTKWLHHLSGLLKAALLVVNAVDEEGRPVLVHCSDG 160

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 33112674 342 WDRTAQVCSVASLLLDPYYRTLKGFMVLIEKDWISFGHKFNHRYGNLDG--DPKEISPVIDQFIECVWQ 408
Cdd:cd14533 161 WDRTPQIVALAELMLDPYYRTIEGFQVLVEREWLDFGHKFADRCGHGVNseDINERCPVFLQWLDCVHQ 229
PTP-MTMR3 cd14586
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 143-408 7.85e-63

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: 211.42  E-value: 7.85e-63
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 143 DNYWQLSDVNRDYRVCDSYPTELYVPRSATAHIIVGSSKFRSRRRFPALSYYCKDSHASICRSSQP-LSGFSARCLEDEQ 221
Cdd:cd14586   5 QNAWRISNINEKYKLCGSYPQELIVPAWITDKELESVASFRSWKRIPAVVYRHQSNGAVIARCGQPeVSWWGWRNADDEH 84

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 222 MLQAIRKA------------NPGS--------------DF-------------------IYVVDTRPKLNAMANRAAGKG 256
Cdd:cd14586  85 LVQSVAKAcasdssscksvlMTGNcsrdfpnggdlsdvEFdssmsnasgveslaiqpqkLLILDARSYAAAVANRAKGGG 164

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 257 YENEDNYSNIKFQFIGIENIHVMRNSLQKMLEVCElKSPSMSDFLWGLENSGWLRHIKAIMDAGIFIAKAVSEEGASVLV 336
Cdd:cd14586 165 CECPEYYPNCEVVFMGMANIHSIRKSFQSLRLLCT-QMPDPANWLSALESTKWLQHLSMLLKSALLVVHAVDRDQRPVLV 243

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 33112674 337 HCSDGWDRTAQVCSVASLLLDPYYRTLKGFMVLIEKDWISFGHKFNHR--YGNLDGDPKEISPVIDQFIECVWQ 408
Cdd:cd14586 244 HCSDGWDRTPQIVALSKLLLDPYYRTIEGFQVLVETEWLDFGHKFADRcgHGENSDDLNERCPVFLQWLDCVHQ 317
PTP-MTMR9 cd14536
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 187-408 1.67e-62

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: 207.19  E-value: 1.67e-62
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 187 RFPALSYYCKDSHASICRSSQPLSGFSA-RCLEDEQMLQA-IRKANPGsdfiYVVDTRPKLNAMANRAAGKGYENEDNYS 264
Cdd:cd14536   2 RFPVLSYYHKKNGMVLMRSSQPLTGPNGkRCKEDEKLLNAvLGGGKRG----YIIDTRSKNVAQQARAKGGGFEPEAHYP 77

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 265 NIKFQFIGIENIHVMRNSLQKMLEVCELKSPSMSDFLWGLENSGWLRHIKAIMDAGIFIAKAVSEEGASVLVHCSDGWDR 344
Cdd:cd14536  78 QWRRIHKPIERYNVLQESLIKLVEACNDQGHSMDKWLSKLESSNWLSHVKEILTTACLVAQCIDREGASVLVHGSEGMDS 157

                       170       180       190       200       210       220
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 33112674 345 TAQVCSVASLLLDPYYRTLKGFMVLIEKDWISFGHKFNHR-----YGNldGDPKEISPVIDQFIECVWQ 408
Cdd:cd14536 158 TLQVTSLAQIILDPDCRTIRGFEALIEREWLQAGHPFQSRcaksaYSN--SKQKFESPVFLLFLDCVWQ 224
PH-GRAM_MTMR6-like cd13210
Myotubularian (MTM) related (MTMR) 7 and 8 proteins Pleckstrin Homology-Glucosyltransferases, ...
 4-103 2.49e-61

Myotubularian (MTM) related (MTMR) 7 and 8 proteins Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR6, MTMR7, and MRMR8 are all member of the myotubularin dual specificity protein phosphatase gene family. They bind to phosphoinositide lipids through its PH-GRAM domain. These proteins also interact with each other as well as MTMR9. They contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an active PTP domain, a SET-interaction domain, and a C-terminal coiled-coil region. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 6 of the 13 MTMRs (MTMRs 5, 9-13) contain naturally occurring substitutions of residues required for catalysis by PTP family enzymes. Although these proteins are predicted to be enzymatically inactive, they are thought to function as antagonists of endogenous phosphatase activity or interaction modules. Most MTMRs contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, a PTP domain (which may be active or inactive), a SET-interaction domain, and a C-terminal coiled-coil region. In addition some members contain DENN domain N-terminal to the PH-GRAM domain and FYVE, PDZ, and PH domains C-terminal to the coiled-coil region. The lipid-binding FYVE domain has been shown to bind phosphotidylinositol-3-phosphate. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. The PH domain family possesses multiple functions including the ability to bind phosphoinositides via its beta1/beta2, beta3/beta4, and beta6/beta7 connecting loops and to other proteins. However, no phosphoinositide binding sites have been found for the MTMRs to date.


Pssm-ID: 270030  Cd Length: 98  Bit Score: 199.43  E-value: 2.49e-61
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674   4 IRTPKVENVRLVDRVSCKKAALGTLYLTATHVIFVEnaPDTRKETWILHSQISTIEKQATTATGCPLLIRCKNFQIVQLV 83
Cdd:cd13210   1 IRTPKVENVRLLDRFSSRKPAVGTLYLTATHLIFVE--PSGKKETWILHSHIASVEKLPLTTAGCPLVIRCKNFQVITFV 78

                        90       100
                ....*....|....*....|
gi 33112674  84 IPQERDCHDVYISLIRLARP 103
Cdd:cd13210  79 IPRERDCHDVYTSLLRLSRP 98
PH-GRAM_MTMR8 cd13345
Myotubularian (MTM) related 8 protein (MTMR8) Pleckstrin Homology-Glucosyltransferases, ...
 1-103 1.74e-50

Myotubularian (MTM) related 8 protein (MTMR8) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR8 is a member of the myotubularin dual specificity protein phosphatase gene family. MTMR8 binds to phosphoinositide lipids through its PH-GRAM domain. MTMR8 can self associate and interacts with MTMR6, MTMR7 and MTMR9. MTMR8 contains a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an active PTP domain, a SET-interaction domain, and a C-terminal coiled-coil region. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 6 of the 13 MTMRs (MTMRs 5, 9-13) contain naturally occurring substitutions of residues required for catalysis by PTP family enzymes. Although these proteins are predicted to be enzymatically inactive, they are thought to function as antagonists of endogenous phosphatase activity or interaction modules. Most MTMRs contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, a PTP domain (which may be active or inactive), a SET-interaction domain, and a C-terminal coiled-coil region. In addition some members contain DENN domain N-terminal to the PH-GRAM domain and FYVE, PDZ, and PH domains C-terminal to the coiled-coil region. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. The PH domain family possesses multiple functions including the ability to bind phosphoinositides via its beta1/beta2, beta3/beta4, and beta6/beta7 connecting loops and to other proteins. However, no phosphoinositide binding sites have been found for the MTMRs to date.


Pssm-ID: 270153  Cd Length: 103  Bit Score: 170.52  E-value: 1.74e-50
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674   1 MEHIRTPKVENVRLVDRVSCKKAALGTLYLTATHVIFVENAPDTRKETWILHSQISTIEKQATTATGCPLLIRCKNFQIV 80
Cdd:cd13345   1 MEHITTPKVENVKLLDRYTNKKPANGTLYLTATHLIYVEASGAARKETWILHHHIATVEKLPLTSLGCPLLIRCKNFRVA 80

                        90       100
                ....*....|....*....|...
gi 33112674  81 QLVIPQERDCHDVYISLIRLARP 103
Cdd:cd13345  81 HFVLDSERDCHEVYISLLKLSQP 103
PTP-MTMR5-like cd14534
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 146-412 2.89e-43

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: 156.76  E-value: 2.89e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 146 WQLSDVNRDYRVCDSYPTELYVPRSATAHIIVGSSKFRSRRRFPALSYYCKDSHASICRS-------------SQPLSGF 212
Cdd:cd14534   1 FRISTANRDYSICRSYPALVVVPQSVSDESLRKVARCYRQGRFPVVTWRHPRTKALLLRSggfhgkgvmgmlkSANTSTS 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 213 SARC--------LEDEQMLQAIrkanpgsdFIYVvdtrpklnaMANRAAGKGYENEdnySNIKFQFIGIE--NIHVMRNS 282
Cdd:cd14534  81 SPTVsssetsssLEQEKYLSAL--------VLYV---------LGEKSQMKGVKAE---SDPKCEFIPVEypEVRQVKAS 140

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 283 LQKMLEVCELKSPSMSD---FLWGLENSGWLRHIKAIMDagifIAKAVSE----EGASVLVHCSDGWDRTAQVCSVASLL 355
Cdd:cd14534 141 FKKLLRACVPSSAPTEPeqsFLKAVEDSEWLQQLQCLMQ----LSGAVVDlldvQGSSVLLCLEDGWDVTTQVSSLSQLL 216

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 33112674 356 LDPYYRTLKGFMVLIEKDWISFGHKFNHRyGNLDGDPKE--ISPVIDQFIECVWQLTEQ 412
Cdd:cd14534 217 LDPYYRTLEGFRVLVEKEWLAFGHRFSHR-SNLTAASQSsgFAPVFLQFLDAVHQIHRQ 274
PH-GRAM_MTMR6 cd13343
Myotubularian (MTM) related (MTMR) 6 protein Pleckstrin Homology-Glucosyltransferases, ...
 1-103 3.91e-43

Myotubularian (MTM) related (MTMR) 6 protein Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR6 is a member of the myotubularin dual specificity protein phosphatase gene family. MTMR6 binds to phosphoinositide lipids through its PH-GRAM domain. It acts as a negative regulator of KCNN4/KCa3.1 channel activity in CD4+ T-cells possibly by decreasing intracellular levels of phosphatidylinositol-3 phosphatase and negatively regulates proliferation of reactivated CD4+ T-cells MTMR6 interacts with MTMR7, MTMR8 and MTMR9. MTMR6 contains a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an active PTP domain, a SET-interaction domain, and a C-terminal coiled-coil region. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 6 of the 13 MTMRs (MTMRs 5, 9-13) contain naturally occurring substitutions of residues required for catalysis by PTP family enzymes. Although these proteins are predicted to be enzymatically inactive, they are thought to function as antagonists of endogenous phosphatase activity or interaction modules. Most MTMRs contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, a PTP domain (which may be active or inactive), a SET-interaction domain, and a C-terminal coiled-coil region. In addition some members contain DENN domain N-terminal to the PH-GRAM domain and FYVE, PDZ, and PH domains C-terminal to the coiled-coil region. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. The PH domain family possesses multiple functions including the ability to bind phosphoinositides via its beta1/beta2, beta3/beta4, and beta6/beta7 connecting loops and to other proteins. However, no phosphoinositide binding sites have been found for the MTMRs to date.


Pssm-ID: 270151  Cd Length: 101  Bit Score: 150.55  E-value: 3.91e-43
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674   1 MEHIRTPKVENVRLVDRVS-CKKAALGTLYLTATHVIFVENapdTRKETWILHSQISTIEKQATTATGCPLLIRCKNFQI 79
Cdd:cd13343   1 MEHIRTTKVEQVKLLDRFStSNKSLTGTLYLTATHLLFIDN---SQQETWILHHHIAPVEKLSLTTSGCPLVIQCKNFRV 77

                        90       100
                ....*....|....*....|....
gi 33112674  80 VQLVIPQERDCHDVYISLIRLARP 103
Cdd:cd13343  78 VHFVVPRERDCHDIYNSLLQLSRP 101
PTP-MTMR5 cd14588
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 146-412 9.38e-41

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: 150.50  E-value: 9.38e-41
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 146 WQLSDVNRDYRVCDSYPTELYVPRSATAHIIVGSSKFRSRRRFPALSYYCKDSHASICRS---------------SQPLS 210
Cdd:cd14588   1 FRISTVNRMYAVCRSYPGLLIVPQSIQDNTIQRISRCYRQNRFPVVCWRNSRTKAVLLRSgglhgkgvvglfksqNAPAA 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 211 GFS---ARCLEDEQMLQAIRKANPGSDFIYVVDT----RPKLNAMANRAAGKGYEnEDNYSNIKFQFIGIENIHVMRNSL 283
Cdd:cd14588  81 GQSqtdSTSLEQEKYLQAVINSMPRYADASGRNTlsgfRAALYIIGDKSQLKGVK-QDPLQQWEVVPIEVFDVRQVKASF 159

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 284 QKMLEVC---ELKSPSMSDFLWGLENSGWLRHIKAIMDAGIFIAKAVsEEGASVLVHCSDGWDRTAQVCSVASLLLDPYY 360
Cdd:cd14588 160 KKLMKACvpsCPSTDPSQTYLRTLEESEWLSQLHKLLQVSVLVVELL-DSGSSVLVSLEDGWDITTQVVSLVQLLSDPYY 238

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|...
gi 33112674 361 RTLKGFMVLIEKDWISFGHKFNHRYGN-LDGDPKEISPVIDQFIECVWQLTEQ 412
Cdd:cd14588 239 RTIEGFRLLVEKEWLSFGHRFSHRGAQtLASQSSGFTPVFLQFLDCVHQIHLQ 291
PTP-MTMR13 cd14589
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 146-412 2.75e-37

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: 140.83  E-value: 2.75e-37
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 146 WQLSDVNRDYRVCDSYPTELYVPRSATAHIIVGSSKFRSRRRFPALSYYCKDSHASICRS-------------SQ----- 207
Cdd:cd14589   1 FRITAVNRMYSLCRSYPGLLVVPQSVQDSSLQKVARCYRHNRLPVVCWKNSKTKAVLLRSggfhgkgvvglfkSQnphsa 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 208 -PLSGFSARCLEDEQMLQAIRKANPGSDFIYVVDTRPKLNAMANRAAGKGYENEDNYSNIKF------QFIGIE--NIHV 278
Cdd:cd14589  81 aPASSESSSSIEQEKYLQALLNAISVHQKMNGNSTLLQSQLLKRQAALYIFGEKSQLRGFKLdfalncEFVPVEfhDIRQ 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 279 MRNSLQKMLEVC---ELKSPSMSDFLWGLENSGWLRHIKAIMDAGIFIAKaVSEEGASVLVHCSDGWDRTAQVCSVASLL 355
Cdd:cd14589 161 VKASFKKLMRACvpsTIPTDSEVTFLKALGESEWFLQLHRIMQLAVVISE-LLESGSSVMVCLEDGWDITTQVVSLVQLL 239

                       250       260       270       280       290
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 33112674 356 LDPYYRTLKGFMVLIEKDWISFGHKFNHRYG-NLDGDPKEISPVIDQFIECVWQLTEQ 412
Cdd:cd14589 240 SDPFYRTLEGFQMLVEKEWLSFGHKFSQRSNlTPNSQGSGFAPIFLQFLDCVHQIHNQ 297
PTP-MTMR10-like cd14537
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 186-408 1.19e-27

protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related phosphoinositide phosphatases 10, 11, and 12; This subgroup of enzymatically inactive phosphatase domains of myotubularins consists of MTMR10, MTMR11, MTMR12, and similar proteins. Beside the phosphatase domain, they contain an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. MTMR10, MTMR11, and MTMR12 are pseudophosphatases that lack the catalytic cysteine in their catalytic pocket. MTMR12 functions as an adapter for the catalytically active myotubularin to regulate its intracellular location.


Pssm-ID: 350385  Cd Length: 200  Bit Score: 110.51  E-value: 1.19e-27
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 186 RRFPALSYYCKdSHASICRSSQPLSGFSARCLEdEQMLQAIRKANPGSDFIYVVDTrpklnamanraagkgyenEDNYSN 265
Cdd:cd14537   1 GRPPVWCWSHP-NGAALVRMAELLPTITDRTQE-NKMLEAIRKSHPNLKKPKVIDL------------------DKLLPS 60

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 266 IKfqfigieNIHVmrnSLQKMLEVCELKSPS---MSDFLW--GLENSGWLRHIKAIMDAGIFIAKAVSEEGASVLVHCSD 340
Cdd:cd14537  61 LQ-------DVQA---AYLKLRELCTPDSSEqfwVQDSKWysLLENTKWLHYVSACLKKASEAAEALESRGRSVVLQESD 130

                       170       180       190       200       210       220       230
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 341 GWDRTAQVCSVASLLLDPYYRTLKGFMVLIEKDWISFGHKFNHRYGNL--DGDPKEISPVIDQFIECVWQ 408
Cdd:cd14537 131 GRDLSCVVSSLVQLLLDPHFRTITGFQSLIQKEWVALGHPFCDRLGHVkpNKTESEESPVFLLFLDCVWQ 200
PTP-MTMR11 cd14595
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 296-409 3.59e-21

protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related phosphoinositide phosphatase 11; Myotubularin related phosphoinositide phosphatase 11 (MTMR11), also called cisplatin resistance-associated protein (hCRA) in humans, is enzymatically inactive and contains a C-terminal coiled-coil domain and an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. MTMR11 is a pseudophosphatase that lacks the catalytic cysteine in its catalytic pocket.


Pssm-ID: 350443  Cd Length: 195  Bit Score: 91.82  E-value: 3.59e-21
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 296 SMSDFLWGLENSGWLRHIKAIMDAGIFIAKAVSEEGASVLVHCSDGWDRTAQVCSVASLLLDPYYRTLKGFMVLIEKDWI 375
Cdd:cd14595  82 SDEKWLSNLEGTRWLDHVRACLRKASEVSCLLAERHRSVILQESEDRDLNCLLSSLVQLLSDPHARTISGFQSLVQKEWV 161

                        90       100       110
                ....*....|....*....|....*....|....
gi 33112674 376 SFGHKFNHRYGNLDGDPKEISPVIDQFIECVWQL 409
Cdd:cd14595 162 VAGHPFLQRLNLTRESDKEESPVFLLFLDCVWQL 195
PTP-MTMR12 cd14594
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 298-409 1.81e-18

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: 84.12  E-value: 1.81e-18
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 298 SDFLW--GLENSGWLRHIKAIMDAGIFIAKAVSEEGASVLVHCSDGWDRTAQVCSVASLLLDPYYRTLKGFMVLIEKDWI 375
Cdd:cd14594  90 TDVKWfsSLESSNWLEIIRQCLKKAVEVVECLEKQNTNVLLTEEEATDLCCVISSLVQIMMDPYCRTKSGFQSLIQKEWV 169

                        90       100       110
                ....*....|....*....|....*....|....
gi 33112674 376 SFGHKFNHRYGNLDGDPKEISPVIDQFIECVWQL 409
Cdd:cd14594 170 MGGHCFLDRCNHLRQNDKEEVPVFLLFLDCVWQL 203
PTP-MTMR10 cd14593
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 275-408 8.30e-17

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: 79.17  E-value: 8.30e-17
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 275 NIHVMRNSLQKMLEVCELKSPSMSDFLW--GLENSGWLRHIKAIMDAGIFIAKAVSEEGASVLVHCSDGWDRTAQVCSVA 352
Cdd:cd14593  60 NIQEIQAAFVKLKQLCVNEPFEETEEKWlsSLESTRWLEYVRAFLKHSAELVYMLESKHVSVILQEEEGRDLSCVVASLV 139

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 33112674 353 SLLLDPYYRTLKGFMVLIEKDWISFGHKFNHRYGNLDGDPKEISPVIDQFIECVWQ 408
Cdd:cd14593 140 QVMLDPYFRTITGFQSLIQKEWVMAGYRFLDRCNHLKKSSKKESPLFLLFLDCVWQ 195
PH-GRAM_MTMR9 cd13211
Myotubularian (MTM) related 9 protein (MTMR9) Pleckstrin Homology-Glucosyltransferases, ...
 1-97 1.08e-16

Myotubularian (MTM) related 9 protein (MTMR9) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR9 is a catalytically inactive phosphatase that plays a role as an adapter for the phosphatase myotubularin to regulate myotubularintracellular location. It contains a Gly residue instead of a conserved Cys residue in the dsPTPase catalytic loop which renders it catalytically inactive as a phosphatase. MTMR9 contains an N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, an inactive PTP domain, a SET interaction domain, and a C-terminal coiled-coil region. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 6 of the 13 MTMRs (MTMRs 5, 9-13) contain naturally occurring substitutions of residues required for catalysis by PTP family enzymes. Although these proteins are predicted to be enzymatically inactive, they are thought to function as antagonists of endogenous phosphatase activity or interaction modules. Most MTMRs contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, a PTP domain (which may be active or inactive), a SET-interaction domain, and a C-terminal coiled-coil region. In addition some members contain DENN domain N-terminal to the PH-GRAM domain and FYVE, PDZ, and PH domains C-terminal to the coiled-coil region. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. The PH domain family possesses multiple functions including the ability to bind phosphoinositides via its beta1/beta2, beta3/beta4, and beta6/beta7 connecting loops and to other proteins. However, no phosphoinositide binding sites have been found for the MTMRs to date.


Pssm-ID: 275398  Cd Length: 99  Bit Score: 75.77  E-value: 1.08e-16
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674   1 MEHIRTPKVENVRLVDRVscKKAALGTLYLTATHVIFvENAPDTRKETWILHSQISTIEK-QATTATGCPLLIRCKNFQI 79
Cdd:cd13211   4 AELIKTPKVDNVVLHRPP--RPAVEGTLCITGHHLIL-SSRQDNAEELWLLHSNIDSVEKkFVGKSSGGTLTLKCKDFRI 80

                        90
                ....*....|....*...
gi 33112674  80 VQLVIPQERDCHDVYISL 97
Cdd:cd13211  81 IQLDIPDMEECLNIASSI 98
PH-GRAM cd10570
Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins ...
 21-97 4.72e-11

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: 59.70  E-value: 4.72e-11
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 33112674  21 KKAALGTLYLTATHVIFVENAPDTRKETWILHSQISTIEKQATTAT-GCPLLIRCKNFQIVQL-VIPQERDCHDVYISL 97
Cdd:cd10570  16 KLPLEGTLYLSTYRLIFSSKADGDETKLVIPLVDITDVEKIAGASFlPSGLIITCKDFRTIKFsFDSEDEAVKVIARVL 94
PTPc_motif smart00404
Protein tyrosine phosphatase, catalytic domain motif;
328-364 4.76e-06

Protein tyrosine phosphatase, catalytic domain motif;


Pssm-ID: 214649 [Multi-domain]  Cd Length: 105  Bit Score: 45.81  E-value: 4.76e-06
                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 33112674    328 SEEGASVLVHCSDGWDRTAQVCSVASLLLDPYYRTLK 364
Cdd:smart00404  36 SESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEAGE 72
PTPc_DSPc smart00012
Protein tyrosine phosphatase, catalytic domain, undefined specificity; Protein tyrosine ...
 328-364 4.76e-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: 45.81  E-value: 4.76e-06
                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 33112674    328 SEEGASVLVHCSDGWDRTAQVCSVASLLLDPYYRTLK 364
Cdd:smart00012  36 SESSGPVVVHCSAGVGRTGTFVAIDILLQQLEAEAGE 72
DUSP3-like cd14515
dual specificity protein phosphatases 3, 13, 26, 27, and similar domains; This family is ...
 245-356 1.31e-04

dual specificity protein phosphatases 3, 13, 26, 27, and similar domains; This family is composed of dual specificity protein phosphatase 3 (DUSP3, also known as VHR), 13B (DUSP13B, also known as TMDP), 26 (DUSP26, also known as MPK8), 13A (DUSP13A, also known as MDSP), dual specificity phosphatase and pro isomerase domain containing 1 (DUPD1), and inactive DUSP27. In general, DUSPs function as protein-serine/threonine phosphatases (EC 3.1.3.16) and protein-tyrosine-phosphatases (EC 3.1.3.48). Members of this family are atypical DUSPs; they contain the catalytic dual specificity phosphatase domain but lack the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. Inactive DUSP27 contains a dual specificity phosphatase-like domain with the active site cysteine substituted to serine.


Pssm-ID: 350365 [Multi-domain]  Cd Length: 148  Bit Score: 42.58  E-value: 1.31e-04
                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 33112674 245 LNAMANRAAGKGYENEDNYSNIKFQFIGIEnihvmrnslqkmleVCELKSPSMSDFLWglensgwlrhikaimDAGIFIA 324
Cdd:cd14515  31 LNAAEGKKNGEVNTNAKFYKGSGIIYLGIP--------------ASDLPTFDISQYFD---------------EAADFID 81

                        90       100       110
                ....*....|....*....|....*....|..
gi 33112674 325 KAVSEEGASVLVHCSDGWDRTAqVCSVASLLL 356
Cdd:cd14515  82 KALSDPGGKVLVHCVEGVSRSA-TLVLAYLMI 112
PTP_DSP_cys cd14494
cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This ...
 293-350 3.03e-04

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: 40.80  E-value: 3.03e-04
                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 33112674 293 KSPSMSDFLWGLENSGWLRHIKAIMDAGIFIAKAVSEEGASVLVHCSDGWDRTAQVCS 350
Cdd:cd14494  18 PLEADSRFLKQLGVTTIVDLTLAMVDRFLEVLDQAEKPGEPVLVHCKAGVGRTGTLVA 75
DUSP13A cd14580
dual specificity protein phosphatase 13 isoform A; Dual specificity protein phosphatase 13 ...
 319-390 4.46e-03

dual specificity protein phosphatase 13 isoform A; Dual specificity protein phosphatase 13 isoform A (DUSP13A), also called branching-enzyme interacting DSP or muscle-restricted DSP (MDSP), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. DUSP13A is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. DUSP13A also functions as a regulator of apoptosis signal-regulating kinase 1 (ASK1), a MAPK kinase kinase, by interacting with its N-terminal domain and inducing ASK1-mediated apoptosis through the activation of caspase-3. This function is independent of phosphatase activity.


Pssm-ID: 350428 [Multi-domain]  Cd Length: 145  Bit Score: 38.20  E-value: 4.46e-03
                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 33112674 319 AGIFIAKAVSEEGASVLVHCSDGWDRTAQVCsVASLLLDPYYRTLKGFMVLIEKDWISFGHKFNHRYGNLDG 390
Cdd:cd14580  73 AAEFIHRALNTPGAKVLVHCAVGVSRSATLV-LAYLMIYHQLSLVQAIKTVKERRWIFPNRGFLKQLRKLDQ 143
DUSP3 cd14579
dual specificity protein phosphatase 3; Dual specificity protein phosphatase 3 (DUSP3), also ...
 318-356 7.97e-03

dual specificity protein phosphatase 3; Dual specificity protein phosphatase 3 (DUSP3), also called vaccinia H1-related phosphatase (VHR), functions as a protein-serine/threonine phosphatase (EC 3.1.3.16) and a protein-tyrosine-phosphatase (EC 3.1.3.48). It deactivates its MAPK substrates by dephosphorylating the threonine and tyrosine residues in the conserved Thr-Xaa-Tyr motif residing in their activation sites. DUSP3 is an atypical DUSP; it contains the catalytic dual specificity phosphatase domain but lacks the N-terminal Cdc25/rhodanese-like domain that is present in typical DUSPs or MKPs. It favors bisphosphorylated substrates over monophosphorylated ones, and prefers pTyr peptides over pSer/pThr peptides. Reported physiological substrates includes MAPKs ERK1/2, JNK, and p38, as well as STAT5, EGFR, and ErbB2. DUSP3 has been linked to breast and prostate cancer, and may also play a role in thrombosis.


Pssm-ID: 350427 [Multi-domain]  Cd Length: 168  Bit Score: 37.82  E-value: 7.97e-03
                        10        20        30
                ....*....|....*....|....*....|....*....
gi 33112674 318 DAGIFIAKAVSEEGASVLVHCSDGWDRTAQVCsVASLLL 356
Cdd:cd14579  95 EAADFIDKALAQKNGRVLVHCREGYSRSPTLV-IAYLML 132
 
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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