Myotubularin protein; This domain family is found in eukaryotes, and is approximately 220 amino acids in length. The family is found in association with pfam02141, pfam03456, pfam03455. This family is the middle region of SBF2, a member of the myotubularin family. Myotubularin-related proteins have been suggested to work in phosphoinositide-mediated signalling events that may also convey control of myelination. Mutations of SBF2 are implicated in Charcot-Marie-Tooth disease.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966630   530 GPPVVSIMDKVTTVF-NSAQRLEVVRNCISFIFENKILETEKTLPAALRALKGKAARQCLTDELGLHVQQNRAILDHQQF 608
Cdd:pfam12335    1 GPPVVSIVDKRGNVFsNSARRLEVLRNCISFIFENKISEARKSLPAVLRALKGKAARLALCEELNQHVQQNRAVLDHQQF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966630   609 DYIIRMMNCTLQDCSSLEEYNIAAALLPLTSAFYRKLAPGVSQFAYTCVQDHPIWTNQQFWETTFYNAVQEQVRSLYLSA 688
Cdd:pfam12335   81 DLVVRLMNCALQDCSSMDEYGVAAALLPLSTAFCRKLCTGVIQFAYTCVQDHPVWKNQQFWEAAFYQDVQKQIRALYLPS 160

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767966630   689 KEDNHAPHLKQK-DKLPDDHYQEKTAMDLAAEQLRLWPTLSKSTQQELVQHEESTVFSQAIHFANLM 754
Cdd:pfam12335  161 DEKNPHISAQGKnTASLASHAEEPSALEIAAEQMRLWPTLSKEKQQELVKSEESTVYSQAIHYANRM 227

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966630 1138 FRITASNRMYSLCRSYPGLLVVPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLLRSGGFHGKGVVGLFKSQNSPQA 1217
Cdd:cd14589     1 FRITAVNRMYSLCRSYPGLLVVPQSVQDSSLQKVARCYRHNRLPVVCWKNSKTKAVLLRSGGFHGKGVVGLFKSQNPHSA 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 767966630 1218 APTsSLESSSSIEQEKYLQALLNAVSVHQKLRGNSTL 1254
Cdd:cd14589    81 APA-SSESSSSIEQEKYLQALLNAISVHQKMNGNSTL 116

Domain always found upstream of DENN domain, found in a variety of signalling proteins; The uDENN domain is part of the tripartite DENN domain. It is always found upstream of the DENN domain itself, which is found in a variety of signalling proteins involved in Rab-mediated processes or regulation of MAPKs signalling pathways. The DENN domain is always encircled on both sides by more divergent domains, called uDENN (for upstream DENN) and dDENN (for downstream DENN). The function of the DENN domain remains to date unclear, although it appears to represent a good candidate for a GTP/GDP exchange activity.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966630      1 MARLADYFIVVGYDHEKPGSGEG-LGKIIQRFPQKDWDDTPFPQGIELFCQPGGWQL--SRERKQPTFFVVVLTDIDSDR 77
Cdd:smart00800    1 PSRLFDYFVVVGLDSDTGPLGRSyKPEILQRYPEKDFEDFPLPDSIPLFCFPEGLDFvtQTSSKDPQFFSFVLTDIDGSR 80

                    ....*....
gi 767966630     78 HYCSCLTFY 86
Cdd:smart00800   81 RYGFCLRFY 89

Myotubularin protein; This domain family is found in eukaryotes, and is approximately 220 amino acids in length. The family is found in association with pfam02141, pfam03456, pfam03455. This family is the middle region of SBF2, a member of the myotubularin family. Myotubularin-related proteins have been suggested to work in phosphoinositide-mediated signalling events that may also convey control of myelination. Mutations of SBF2 are implicated in Charcot-Marie-Tooth disease.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966630   530 GPPVVSIMDKVTTVF-NSAQRLEVVRNCISFIFENKILETEKTLPAALRALKGKAARQCLTDELGLHVQQNRAILDHQQF 608
Cdd:pfam12335    1 GPPVVSIVDKRGNVFsNSARRLEVLRNCISFIFENKISEARKSLPAVLRALKGKAARLALCEELNQHVQQNRAVLDHQQF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966630   609 DYIIRMMNCTLQDCSSLEEYNIAAALLPLTSAFYRKLAPGVSQFAYTCVQDHPIWTNQQFWETTFYNAVQEQVRSLYLSA 688
Cdd:pfam12335   81 DLVVRLMNCALQDCSSMDEYGVAAALLPLSTAFCRKLCTGVIQFAYTCVQDHPVWKNQQFWEAAFYQDVQKQIRALYLPS 160

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767966630   689 KEDNHAPHLKQK-DKLPDDHYQEKTAMDLAAEQLRLWPTLSKSTQQELVQHEESTVFSQAIHFANLM 754
Cdd:pfam12335  161 DEKNPHISAQGKnTASLASHAEEPSALEIAAEQMRLWPTLSKEKQQELVKSEESTVYSQAIHYANRM 227

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966630 1138 FRITASNRMYSLCRSYPGLLVVPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLLRSGGFHGKGVVGLFKSQNSPQA 1217
Cdd:cd14589     1 FRITAVNRMYSLCRSYPGLLVVPQSVQDSSLQKVARCYRHNRLPVVCWKNSKTKAVLLRSGGFHGKGVVGLFKSQNPHSA 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 767966630 1218 APTsSLESSSSIEQEKYLQALLNAVSVHQKLRGNSTL 1254
Cdd:cd14589    81 APA-SSESSSSIEQEKYLQALLNAISVHQKMNGNSTL 116

Myotubularian (MTM) related 13 protein Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR13 (also called SBF2/SET binding factor 2) is a catalytically inactive phosphatase that plays a role as an adapter for the phosphatase myotubularin to regulate myotubularintracellular location. It contains a Leu residue instead of a conserved Cys residue in the dsPTPase catalytic loop which renders it catalytically inactive as a phosphatase. MTMR13 has high sequence similarity to MTMR5 and has recently been shown to be a second gene mutated in type 4B Charcot-Marie-Tooth syndrome. Both MTMR5 and MTMR13 contain an N-terminal DENN domain, a PH-GRAM domain, an inactive PTP domain, a SET interaction domain, a coiled-coil domain, and a C-terminal PH domain. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 6 of the 13 MTMRs (MTMRs 5, 9-13) contain naturally occurring substitutions of residues required for catalysis by PTP family enzymes. Although these proteins are predicted to be enzymatically inactive, they are thought to function as antagonists of endogenous phosphatase activity or interaction modules. Most MTMRs contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, a PTP domain (which may be active or inactive), a SET-interaction domain, and a C-terminal coiled-coil region. In addition some members contain DENN domain N-terminal to the PH-GRAM domain and FYVE, PDZ, and PH domains C-terminal to the coiled-coil region. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. The PH domain family possesses multiple functions including the ability to bind phosphoinositides via its beta1/beta2, beta3/beta4, and beta6/beta7 connecting loops and to other proteins. However, no phosphoinositide binding sites have been found for the MTMRs to date.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966630  882 EEIVCEGLRVLLDPDGREEATGGLLGGPQLLPAEGALFLTTYRILFRGTPHDQLVGEQTVVRSFPIASITKEKKITMQNQ 961
Cdd:cd13339     1 EEFVCEGLRVLLDPDGREEATGGLLGGPHILPAEGALFLTTYRIIFKGTPHDQLVGEQTVIRSFPIASITKEKKITIQNQ 80

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 767966630  962 LQQNMQEGLQITSASFQLIKVAFDEEVSPEVVEIFKKQL 1000
Cdd:cd13339    81 LQQNMQEGLQITSASFQLIKVAFDEEVSPEVVEIFKKQL 119

uDENN domain; This region is always found associated with pfam02141. It is predicted to form an all beta domain.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966630    25 GKIIQRFPQKDWDDTPFPQGIELFCQPGGWQLSRERKqPTFFVVVLTDIDSDRHYCSCLT 84
Cdd:pfam03456    1 PEVLDRYPEDDWSDPPLPDGIPMFCFPEGLETLSSRE-PTFFSFVLTDEDGSRLYGACLT 59

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966630  1116 RDYQRLGLGTisgsssrsrPEYFRITASNRMYSLCRSYPGLLVVPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLL 1195
Cdd:pfam06602   12 AEFARQGLPS---------KDEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHKENGAVIT 82

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 767966630  1196 RSggfhGKGVVGLFKSQNspqaaptsslessssIEQEKYLQALLNAVSVHQKLRG 1250
Cdd:pfam06602   83 RS----SQPLVGLNGKRS---------------IEDEKLLQAIFKSSNPYSAKKL 118

dDENN domain; This region is always found associated with pfam02141. It is predicted to form a globular domain. Although not statistically supported it has been suggested that this domain may be similar to members of the Rho/Rac/Cdc42 GEF family. This N-terminal region of DENN folds into a longin module, consisting of a central antiparallel beta-sheet layered between helix H1 and helices H2 and H3 (strands S1-S5). Rab35 interacts with dDENN via residues in helix 1 and in the loop S3-S4.

                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 767966630   387 FHKTAFLGQRGLVENDFLTKVLSGMAFAGFVSERG-PPYRSCDLFDEL 433
Cdd:pfam03455    1 FDKEAFLKSLPSDSRPFLSQFLETQMFNEFIEERLeSSDPSIDLFDEE 48

Myotubularin protein; This domain family is found in eukaryotes, and is approximately 220 amino acids in length. The family is found in association with pfam02141, pfam03456, pfam03455. This family is the middle region of SBF2, a member of the myotubularin family. Myotubularin-related proteins have been suggested to work in phosphoinositide-mediated signalling events that may also convey control of myelination. Mutations of SBF2 are implicated in Charcot-Marie-Tooth disease.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966630   530 GPPVVSIMDKVTTVF-NSAQRLEVVRNCISFIFENKILETEKTLPAALRALKGKAARQCLTDELGLHVQQNRAILDHQQF 608
Cdd:pfam12335    1 GPPVVSIVDKRGNVFsNSARRLEVLRNCISFIFENKISEARKSLPAVLRALKGKAARLALCEELNQHVQQNRAVLDHQQF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966630   609 DYIIRMMNCTLQDCSSLEEYNIAAALLPLTSAFYRKLAPGVSQFAYTCVQDHPIWTNQQFWETTFYNAVQEQVRSLYLSA 688
Cdd:pfam12335   81 DLVVRLMNCALQDCSSMDEYGVAAALLPLSTAFCRKLCTGVIQFAYTCVQDHPVWKNQQFWEAAFYQDVQKQIRALYLPS 160

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767966630   689 KEDNHAPHLKQK-DKLPDDHYQEKTAMDLAAEQLRLWPTLSKSTQQELVQHEESTVFSQAIHFANLM 754
Cdd:pfam12335  161 DEKNPHISAQGKnTASLASHAEEPSALEIAAEQMRLWPTLSKEKQQELVKSEESTVYSQAIHYANRM 227

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966630 1138 FRITASNRMYSLCRSYPGLLVVPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLLRSGGFHGKGVVGLFKSQNSPQA 1217
Cdd:cd14589     1 FRITAVNRMYSLCRSYPGLLVVPQSVQDSSLQKVARCYRHNRLPVVCWKNSKTKAVLLRSGGFHGKGVVGLFKSQNPHSA 80

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 767966630 1218 APTsSLESSSSIEQEKYLQALLNAVSVHQKLRGNSTL 1254
Cdd:cd14589    81 APA-SSESSSSIEQEKYLQALLNAISVHQKMNGNSTL 116

Myotubularian (MTM) related 13 protein Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR13 (also called SBF2/SET binding factor 2) is a catalytically inactive phosphatase that plays a role as an adapter for the phosphatase myotubularin to regulate myotubularintracellular location. It contains a Leu residue instead of a conserved Cys residue in the dsPTPase catalytic loop which renders it catalytically inactive as a phosphatase. MTMR13 has high sequence similarity to MTMR5 and has recently been shown to be a second gene mutated in type 4B Charcot-Marie-Tooth syndrome. Both MTMR5 and MTMR13 contain an N-terminal DENN domain, a PH-GRAM domain, an inactive PTP domain, a SET interaction domain, a coiled-coil domain, and a C-terminal PH domain. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 6 of the 13 MTMRs (MTMRs 5, 9-13) contain naturally occurring substitutions of residues required for catalysis by PTP family enzymes. Although these proteins are predicted to be enzymatically inactive, they are thought to function as antagonists of endogenous phosphatase activity or interaction modules. Most MTMRs contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, a PTP domain (which may be active or inactive), a SET-interaction domain, and a C-terminal coiled-coil region. In addition some members contain DENN domain N-terminal to the PH-GRAM domain and FYVE, PDZ, and PH domains C-terminal to the coiled-coil region. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. The PH domain family possesses multiple functions including the ability to bind phosphoinositides via its beta1/beta2, beta3/beta4, and beta6/beta7 connecting loops and to other proteins. However, no phosphoinositide binding sites have been found for the MTMRs to date.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966630  882 EEIVCEGLRVLLDPDGREEATGGLLGGPQLLPAEGALFLTTYRILFRGTPHDQLVGEQTVVRSFPIASITKEKKITMQNQ 961
Cdd:cd13339     1 EEFVCEGLRVLLDPDGREEATGGLLGGPHILPAEGALFLTTYRIIFKGTPHDQLVGEQTVIRSFPIASITKEKKITIQNQ 80

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 767966630  962 LQQNMQEGLQITSASFQLIKVAFDEEVSPEVVEIFKKQL 1000
Cdd:cd13339    81 LQQNMQEGLQITSASFQLIKVAFDEEVSPEVVEIFKKQL 119

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966630 1138 FRITASNRMYSLCRSYPGLLVVPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLLRSGGFHGKGVVGLFKSQNSPQA 1217
Cdd:cd14534     1 FRISTANRDYSICRSYPALVVVPQSVSDESLRKVARCYRQGRFPVVTWRHPRTKALLLRSGGFHGKGVMGMLKSANTSTS 80

                          90       100
                  ....*....|....*....|...
gi 767966630 1218 APTSSLE-SSSSIEQEKYLQALL 1239
Cdd:cd14534    81 SPTVSSSeTSSSLEQEKYLSALV 103

Myotubularian (MTM) related 5 protein (MTMR5) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR5 (also called SBF1/SET binding factor 1) is a catalytically inactive phosphatase that plays a role as an adapter for the phosphatase myotubularin to regulate myotubularintracellular location. It lacks several amino acids in the dsPTPase catalytic pocket which renders it catalytically inactive as a phosphatase. MTMR5 is the most well-studied inactive member of this family and has been implicated in cellular growth control and oncogenic transformation. MTMR5 and MTMR13 contain an N-terminal DENN domain, a PH-GRAM domain, an inactive PTP domain, a SET interaction domain, a coiled-coil domain, and a C-terminal PH domain. Myotubularin-related proteins are a subfamily of protein tyrosine phosphatases (PTPs) that dephosphorylate D3-phosphorylated inositol lipids. Mutations in this family cause the human neuromuscular disorders myotubular myopathy and type 4B Charcot-Marie-Tooth syndrome. 6 of the 13 MTMRs (MTMRs 5, 9-13) contain naturally occurring substitutions of residues required for catalysis by PTP family enzymes. Although these proteins are predicted to be enzymatically inactive, they are thought to function as antagonists of endogenous phosphatase activity or interaction modules. Most MTMRs contain a N-terminal PH-GRAM domain, a Rac-induced recruitment domain (RID) domain, a PTP domain (which may be active or inactive), a SET-interaction domain, and a C-terminal coiled-coil region. In addition some members contain DENN domain N-terminal to the PH-GRAM domain and FYVE, PDZ, and PH domains C-terminal to the coiled-coil region. The GRAM domain, found in myotubularins, glucosyltransferases, and other putative membrane-associated proteins, is part of a larger motif with a pleckstrin homology (PH) domain fold. The PH domain family possesses multiple functions including the ability to bind phosphoinositides via its beta1/beta2, beta3/beta4, and beta6/beta7 connecting loops and to other proteins. However, no phosphoinositide binding sites have been found for the MTMRs to date.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966630  882 EEIVCEGLRVLLDPDGREEATGGLLGGPQLLPAEGALFLTTYRILFRGTPHDQLVGEQTVVRSFPIASITKEKKITMQNQ 961
Cdd:cd13340     1 EECVMDGLRVYLLPDGREEASGGSLGGPPLLPAEGAIFLTTYRVIFKGTPTDPLVGEQVVVRSFPVASLTKEKRISVQAQ 80

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 767966630  962 LQQNMQEGLQITSASFQLIKVAFDEEVSPEVVEIFKKQL 1000
Cdd:cd13340    81 MDQFLQEGLQLRSCTFQLLKIAFDEEVASDSAEVFRKHL 119

uDENN domain; This region is always found associated with pfam02141. It is predicted to form an all beta domain.

                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966630    25 GKIIQRFPQKDWDDTPFPQGIELFCQPGGWQLSRERKqPTFFVVVLTDIDSDRHYCSCLT 84
Cdd:pfam03456    1 PEVLDRYPEDDWSDPPLPDGIPMFCFPEGLETLSSRE-PTFFSFVLTDEDGSRLYGACLT 59

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966630  1116 RDYQRLGLGTisgsssrsrPEYFRITASNRMYSLCRSYPGLLVVPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLL 1195
Cdd:pfam06602   12 AEFARQGLPS---------KDEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHKENGAVIT 82

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 767966630  1196 RSggfhGKGVVGLFKSQNspqaaptsslessssIEQEKYLQALLNAVSVHQKLRG 1250
Cdd:pfam06602   83 RS----SQPLVGLNGKRS---------------IEDEKLLQAIFKSSNPYSAKKL 118

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.

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 767966630 1138 FRITASNRMYSLCRSYPGLLVVPQAVQDSSLPRVARCYRHNRLPVVCWKNSRSGTLLLR 1196
Cdd:cd14587     3 WRVSEINSNYKLCSSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLRNGAVIAR 61

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

                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767966630    879 LPGEEIVCEGLRVLLDPDGReeatggllggpqllpAEGALFLTTYRILFRGTPHDQLvgeqtVVRSFPIASITKEKKIT 957
Cdd:smart00568    2 LPEEEKLIADYSCYLSRTGP---------------VQGRLYISNYRLCFRSNLPGKL-----TKVVIPLADITRIEKST 60

Stabilization of polarity axis; Swiss:Q99222 has been shown to interact with the outer plaque of the spindle pole body. In Aspergillus nidulans the protein member is necessary for stabilization of the polarity axes during septation. and in S. cerevisiae it functions as a polarization-specific docking factor.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767966630   208 IQNVLSLFCAVLTENKVLF--HSASFQRLSDACRALESLMFPL-------KYSYPYIPIlpaQLLEVLSSPTPFIIGVHS 278
Cdd:pfam08616   12 TPPIILLINALLTSKRIIFlsYQRSAGEVSEFVLALCNLISGGfvlrgftNNSFPYVDL---SKLDALRKVPGYIAGVTN 88

                           90       100
                   ....*....|....*....|....
gi 767966630   279 VFKTDVHELLDVIIaDLDGGTIKI 302
Cdd:pfam08616   89 PIFENQDQWWDVLC-DLDSGSVKL 111

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.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 767966630 1117 DYQRLGLGTisgsssrsrpEYFRITASNRMYSLCRSYPGLLVVPQAVQDSSLPRVARCYRHNRLPVVCW 1185
Cdd:cd14584    10 DFQRMGIPN----------DYWEITDANKNYEICSTYPPELVVPKSASKATVVGSSKFRSRGRFPVLSY 68