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Conserved domains on  [gi|1622837365|ref|XP_028683348|]
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myotubularin-related protein 5 isoform X1 [Macaca mulatta]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PTP_DSP_cys super family cl28904
cys-based protein tyrosine phosphatase and dual-specificity phosphatase superfamily; This ...
 1312-1684 0e+00

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.


The actual alignment was detected with superfamily member cd14588:

Pssm-ID: 475123 [Multi-domain]  Cd Length: 291  Bit Score: 574.22  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1312 FRISPVNRMYAICRSYPGLLIVPQSVQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLLRSGGLHGKGVVGLFKAQNAPSP 1391
Cdd:cd14588      1 FRISTVNRMYAVCRSYPGLLIVPQSIQDNTIQRISRCYRQNRFPVVCWRNSRTKAVLLRSGGLHGKGVVGLFKSQNAPAA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1392 GQSQADSSSLEQEKYLQAVVSSMPRYADASGRNTLSGFssahmgshvpsprarvttlsnpmaasasrrtaprgkwgsvrt 1471
Cdd:cd14588     81 GQSQTDSTSLEQEKYLQAVINSMPRYADASGRNTLSGF------------------------------------------ 118

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1472 sgrssglgtevgsrlagrdtlappqanggppdpgflrpqRAALYILGDKAQLKGVRPDPLQQWELVPIEVFEARQVKASF 1551
Cdd:cd14588    119 ---------------------------------------RAALYIIGDKSQLKGVKQDPLQQWEVVPIEVFDVRQVKASF 159

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1552 KKLLKACVPGCPAAePSPASFLRSLEDSEWLIQIHKLLQVSVLVVELLDSGSSVLVGLEDGWDITTQVVSLVQLLSDPFY 1631
Cdd:cd14588    160 KKLMKACVPSCPST-DPSQTYLRTLEESEWLSQLHKLLQVSVLVVELLDSGSSVLVSLEDGWDITTQVVSLVQLLSDPYY 238

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1622837365 1632 RTLEGFRLLLEKEWLSFGHRFSHRGAHTLAGQSSGFTPVFLQFLDCVHQVHLQ 1684
Cdd:cd14588    239 RTIEGFRLLVEKEWLSFGHRFSHRGAQTLASQSSGFTPVFLQFLDCVHQIHLQ 291
SBF2 pfam12335
Myotubularin protein; This domain family is found in eukaryotes, and is approximately 220 ...
 704-926 1.21e-135

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.


:

Pssm-ID: 463536  Cd Length: 227  Bit Score: 422.11  E-value: 1.21e-135
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365  704 GPPMTAILERCSGLHVNSARRLEVVRNCISYVFEGKMLEAKKLLPAVLRALKGRAARRCLAQELHLHVQQNRAVLDHQQF 783
Cdd:pfam12335    1 GPPVVSIVDKRGNVFSNSARRLEVLRNCISFIFENKISEARKSLPAVLRALKGKAARLALCEELNQHVQQNRAVLDHQQF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365  784 DFVVRMMNCCLQDCTSLDEHGIAAALLPLVTAFCRKLSPGVTQFAYSCVQEHVVWSTPQFWEAMFYGDVQTHIRALYLEP 863
Cdd:pfam12335   81 DLVVRLMNCALQDCSSMDEYGVAAALLPLSTAFCRKLCTGVIQFAYTCVQDHPVWKNQQFWEAAFYQDVQKQIRALYLPS 160

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1622837365  864 TEDLAPAQEVGEAP----SQEDERSALDVASEQRRLWPTLSREKQQELVQKEESTVFSQAIHYANRM 926
Cdd:pfam12335  161 DEKNPHISAQGKNTaslaSHAEEPSALEIAAEQMRLWPTLSKEKQQELVKSEESTVYSQAIHYANRM 227
PH-like super family cl17171
Pleckstrin homology-like domain; The PH-like family includes the PH domain, both the Shc-like ...
 1055-1173 6.52e-68

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


The actual alignment was detected with superfamily member cd13340:

Pssm-ID: 473070  Cd Length: 119  Bit Score: 224.36  E-value: 6.52e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1055 EECVLDGLRVYLLPDGREEGAGGSAGGPALLPAEGAVFLTTYRVIFTGMPTDPLVGEQVVVRSFPVAALTKEKRISVQTP 1134
Cdd:cd13340      1 EECVMDGLRVYLLPDGREEASGGSLGGPPLLPAEGAIFLTTYRVIFKGTPTDPLVGEQVVVRSFPVASLTKEKRISVQAQ 80

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1622837365 1135 VDQLLQDGLQLRSCTFQLLKMAFDEEVGSDSAELFRKQL 1173
Cdd:cd13340     81 MDQFLQEGLQLRSCTFQLLKIAFDEEVASDSAEVFRKHL 119
PH_Sbf1_hMTMR5 cd01235
Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a ...
 1948-2053 4.52e-62

Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a myotubularin-related pseudo-phosphatase. Both Sbf1 and myotubularin interact with the SET domains of Hrx and other epigenetic regulatory proteins, but Sbf1 lacks phosphatase activity due to several amino acid changes in its structurally preserved catalytic pocket. It contains pleckstrin (PH), GEF, and myotubularin homology domains that are thought to be responsible for signaling and growth control. Sbf1 functions as an inhibitor of cellular growth. The N-terminal GEF homology domain serves to inhibit the transforming effects of Sbf1. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


:

Pssm-ID: 269941  Cd Length: 106  Bit Score: 207.18  E-value: 4.52e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1948 ENRSYEGTLYKKGAFMKPWKARWFVLDKTKHQLRYYDHRVDTECKGVIDLAEVEAVAPGTPTMGAPKTVDEKAFFDVKTT 2027
Cdd:cd01235      1 ENRTHEGYLYKRGALLKGWKQRWFVLDSTKHQLRYYESREDTKCKGFIDLAEVESVTPATPIIGAPKRADEGAFFDLKTN 80

                           90       100
                   ....*....|....*....|....*.
gi 1622837365 2028 RRVYNFCAQDVPSAQQWVDRIQSCLS 2053
Cdd:cd01235     81 KRVYNFCAFDAESAQQWIEKIQSCLS 106
DENN smart00799
Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN; The ...
 283-472 3.38e-60

Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN; The DENN domain 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.


:

Pssm-ID: 214823  Cd Length: 183  Bit Score: 204.74  E-value: 3.38e-60
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365   283 APKTLVLVSRLDHAEVFRNSLGLIYAIHVEGLNVCLENVIgNLLTCTVPLAGGSQldsveegaRTISLGAGDRQVIQTPL 362
Cdd:smart00799    1 APKCICILSRLPFFELFRKILNELYRLLPSSSNLPLELLI-SLLLYPVPPPGGSL--------VLVSLGPGDLIELQRPL 71

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365   363 ADSLPVSRCSVALLFRQLGITNVLSLFCAALTEHKVLFLSRSYQRLADACRGLLALLFPLRYSFTYVPILPAQLLEVLST 442
Cdd:smart00799   72 DSSLPLIDFSLHELFECLGVENILQLFAALLLERRIIFTSSNLSTLSAVIEALLALLYPFVWQHIYIPILPASLLDVLSA 151

                           170       180       190
                    ....*....|....*....|....*....|..
gi 1622837365   443 PTPFIIGVNAAFQAETQELL--DVIVADLDGG 472
Cdd:smart00799  152 PTPFIIGVHSSYFEEVKELPdeDVVVVDLDTG 183
uDENN pfam03456
uDENN domain; This region is always found associated with pfam02141. It is predicted to form ...
 178-237 3.90e-23

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


:

Pssm-ID: 460926  Cd Length: 59  Bit Score: 94.21  E-value: 3.90e-23
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365  178 GQILQRFPEKDWEDNPFPQGIELFCQPSGWQLCPERnPPTFFVAVLTDINSERHYCACLT 237
Cdd:pfam03456    1 PEVLDRYPEDDWSDPPLPDGIPMFCFPEGLETLSSR-EPTFFSFVLTDEDGSRLYGACLT 59
dDENN smart00801
Domain always found downstream of DENN domain, found in a variety of signalling proteins; The ...
 526-594 4.05e-19

Domain always found downstream of DENN domain, found in a variety of signalling proteins; The dDENN domain is part of the tripartite DENN domain. It is always found downstream 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.


:

Pssm-ID: 129037  Cd Length: 69  Bit Score: 83.11  E-value: 4.05e-19
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1622837365   526 DKELRAVFLRLFAQLLQGYRWCLHVVRVHPEPVIRFHKAAFLGQRGLVEDDFLMKVLEGMAFAGFVSER 594
Cdd:smart00801    1 NDEIREAFLRFFVNLFGGYRNFLRELRKEPGPVITFDKESFLKSRPSSERPFLSKFLETQMFSQFIEER 69
PHA03247 super family cl33720
large tegument protein UL36; Provisional
 34-156 5.20e-03

large tegument protein UL36; Provisional


The actual alignment was detected with superfamily member PHA03247:

Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 42.23  E-value: 5.20e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365   34 PHPSPPRmeqlSPRKDPsrnravkygPLWSQRARGRQLPLPETFPTVAEDRPEAFPA-----RPRRDRKRSLRGRGQRAT 108
Cdd:PHA03247  2614 PSPLPPD----THAPDP---------PPPSPSPAANEPDPHPPPTVPPPERPRDDPApgrvsRPRRARRLGRAAQASSPP 2680

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1622837365  109 RLFHARGVKDP----DELEHPQLPSDNTEDRPPPLLKALVPPTNQTEPGEAS 156
Cdd:PHA03247  2681 QRPRRRAARPTvgslTSLADPPPPPPTPEPAPHALVSATPLPPGPAAARQAS 2732
 
Name Accession Description Interval E-value
PTP-MTMR5 cd14588
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1312-1684 0e+00

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: 574.22  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1312 FRISPVNRMYAICRSYPGLLIVPQSVQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLLRSGGLHGKGVVGLFKAQNAPSP 1391
Cdd:cd14588      1 FRISTVNRMYAVCRSYPGLLIVPQSIQDNTIQRISRCYRQNRFPVVCWRNSRTKAVLLRSGGLHGKGVVGLFKSQNAPAA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1392 GQSQADSSSLEQEKYLQAVVSSMPRYADASGRNTLSGFssahmgshvpsprarvttlsnpmaasasrrtaprgkwgsvrt 1471
Cdd:cd14588     81 GQSQTDSTSLEQEKYLQAVINSMPRYADASGRNTLSGF------------------------------------------ 118

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1472 sgrssglgtevgsrlagrdtlappqanggppdpgflrpqRAALYILGDKAQLKGVRPDPLQQWELVPIEVFEARQVKASF 1551
Cdd:cd14588    119 ---------------------------------------RAALYIIGDKSQLKGVKQDPLQQWEVVPIEVFDVRQVKASF 159

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1552 KKLLKACVPGCPAAePSPASFLRSLEDSEWLIQIHKLLQVSVLVVELLDSGSSVLVGLEDGWDITTQVVSLVQLLSDPFY 1631
Cdd:cd14588    160 KKLMKACVPSCPST-DPSQTYLRTLEESEWLSQLHKLLQVSVLVVELLDSGSSVLVSLEDGWDITTQVVSLVQLLSDPYY 238

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1622837365 1632 RTLEGFRLLLEKEWLSFGHRFSHRGAHTLAGQSSGFTPVFLQFLDCVHQVHLQ 1684
Cdd:cd14588    239 RTIEGFRLLVEKEWLSFGHRFSHRGAQTLASQSSGFTPVFLQFLDCVHQIHLQ 291
SBF2 pfam12335
Myotubularin protein; This domain family is found in eukaryotes, and is approximately 220 ...
 704-926 1.21e-135

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.


Pssm-ID: 463536  Cd Length: 227  Bit Score: 422.11  E-value: 1.21e-135
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365  704 GPPMTAILERCSGLHVNSARRLEVVRNCISYVFEGKMLEAKKLLPAVLRALKGRAARRCLAQELHLHVQQNRAVLDHQQF 783
Cdd:pfam12335    1 GPPVVSIVDKRGNVFSNSARRLEVLRNCISFIFENKISEARKSLPAVLRALKGKAARLALCEELNQHVQQNRAVLDHQQF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365  784 DFVVRMMNCCLQDCTSLDEHGIAAALLPLVTAFCRKLSPGVTQFAYSCVQEHVVWSTPQFWEAMFYGDVQTHIRALYLEP 863
Cdd:pfam12335   81 DLVVRLMNCALQDCSSMDEYGVAAALLPLSTAFCRKLCTGVIQFAYTCVQDHPVWKNQQFWEAAFYQDVQKQIRALYLPS 160

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1622837365  864 TEDLAPAQEVGEAP----SQEDERSALDVASEQRRLWPTLSREKQQELVQKEESTVFSQAIHYANRM 926
Cdd:pfam12335  161 DEKNPHISAQGKNTaslaSHAEEPSALEIAAEQMRLWPTLSKEKQQELVKSEESTVYSQAIHYANRM 227
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
 1290-1719 1.69e-99

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: 323.66  E-value: 1.69e-99
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1290 RDYQRLGLGTlssslsrakSEPFRISPVNRMYAICRSYPGLLIVPQSVQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLL 1369
Cdd:pfam06602   12 AEFARQGLPS---------KDEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHKENGAVIT 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1370 RSgglhgkgvvglfkAQnaPSPGQSQAdsSSLEQEKYLQAVVSSmpryadasgrntlsgfssahmgshvpsprarvttls 1449
Cdd:pfam06602   83 RS-------------SQ--PLVGLNGK--RSIEDEKLLQAIFKS------------------------------------ 109

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1450 npmaasasrrtaprgkwgsvrtsgrssglgtevgsrlagrdtlappqANGGPPDPGFLRPQRAALYILGDKAQLKGVRP- 1528
Cdd:pfam06602  110 -----------------------------------------------SNPYSAKKLYIVDARPKLNAMANRAKGGGYENe 142

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1529 DPLQQWELVPIEVFEARQVKASFKKLLKACVPgcpaAEPSPASFLRSLEDSEWLIQIHKLLQVSVLVVELLDS-GSSVLV 1607
Cdd:pfam06602  143 DNYPNCKKIFLGIENIHVMRDSLNKLVEACND----RSPSMDKWLSRLESSGWLKHIKAILDGACLIAQAVDLeGSSVLV 218

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1608 GLEDGWDITTQVVSLVQLLSDPFYRTLEGFRLLLEKEWLSFGHRFSHRGAHTLAGQSSGFT-PVFLQFLDCVHQVHLQFP 1686
Cdd:pfam06602  219 HCSDGWDRTAQLTSLAQLLLDPYYRTIEGFQVLIEKEWLSFGHKFADRCGHLAGFTDSKERsPVFLQFLDCVWQLLRQFP 298

                          410       420       430
                   ....*....|....*....|....*....|...
gi 1622837365 1687 MEFEFSQFYLKFLGYHHVSRRFRTFLLDSDYER 1719
Cdd:pfam06602  299 CAFEFNERFLIRLLYHLYSCQFGTFLCNSEKER 331
PH-GRAM_MTMR5 cd13340
Myotubularian (MTM) related 5 protein (MTMR5) Pleckstrin Homology-Glucosyltransferases, ...
 1055-1173 6.52e-68

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.


Pssm-ID: 275417  Cd Length: 119  Bit Score: 224.36  E-value: 6.52e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1055 EECVLDGLRVYLLPDGREEGAGGSAGGPALLPAEGAVFLTTYRVIFTGMPTDPLVGEQVVVRSFPVAALTKEKRISVQTP 1134
Cdd:cd13340      1 EECVMDGLRVYLLPDGREEASGGSLGGPPLLPAEGAIFLTTYRVIFKGTPTDPLVGEQVVVRSFPVASLTKEKRISVQAQ 80

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1622837365 1135 VDQLLQDGLQLRSCTFQLLKMAFDEEVGSDSAELFRKQL 1173
Cdd:cd13340     81 MDQFLQEGLQLRSCTFQLLKIAFDEEVASDSAEVFRKHL 119
PH_Sbf1_hMTMR5 cd01235
Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a ...
 1948-2053 4.52e-62

Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a myotubularin-related pseudo-phosphatase. Both Sbf1 and myotubularin interact with the SET domains of Hrx and other epigenetic regulatory proteins, but Sbf1 lacks phosphatase activity due to several amino acid changes in its structurally preserved catalytic pocket. It contains pleckstrin (PH), GEF, and myotubularin homology domains that are thought to be responsible for signaling and growth control. Sbf1 functions as an inhibitor of cellular growth. The N-terminal GEF homology domain serves to inhibit the transforming effects of Sbf1. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269941  Cd Length: 106  Bit Score: 207.18  E-value: 4.52e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1948 ENRSYEGTLYKKGAFMKPWKARWFVLDKTKHQLRYYDHRVDTECKGVIDLAEVEAVAPGTPTMGAPKTVDEKAFFDVKTT 2027
Cdd:cd01235      1 ENRTHEGYLYKRGALLKGWKQRWFVLDSTKHQLRYYESREDTKCKGFIDLAEVESVTPATPIIGAPKRADEGAFFDLKTN 80

                           90       100
                   ....*....|....*....|....*.
gi 1622837365 2028 RRVYNFCAQDVPSAQQWVDRIQSCLS 2053
Cdd:cd01235     81 KRVYNFCAFDAESAQQWIEKIQSCLS 106
DENN smart00799
Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN; The ...
 283-472 3.38e-60

Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN; The DENN domain 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.


Pssm-ID: 214823  Cd Length: 183  Bit Score: 204.74  E-value: 3.38e-60
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365   283 APKTLVLVSRLDHAEVFRNSLGLIYAIHVEGLNVCLENVIgNLLTCTVPLAGGSQldsveegaRTISLGAGDRQVIQTPL 362
Cdd:smart00799    1 APKCICILSRLPFFELFRKILNELYRLLPSSSNLPLELLI-SLLLYPVPPPGGSL--------VLVSLGPGDLIELQRPL 71

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365   363 ADSLPVSRCSVALLFRQLGITNVLSLFCAALTEHKVLFLSRSYQRLADACRGLLALLFPLRYSFTYVPILPAQLLEVLST 442
Cdd:smart00799   72 DSSLPLIDFSLHELFECLGVENILQLFAALLLERRIIFTSSNLSTLSAVIEALLALLYPFVWQHIYIPILPASLLDVLSA 151

                           170       180       190
                    ....*....|....*....|....*....|..
gi 1622837365   443 PTPFIIGVNAAFQAETQELL--DVIVADLDGG 472
Cdd:smart00799  152 PTPFIIGVHSSYFEEVKELPdeDVVVVDLDTG 183
DENN pfam02141
DENN (AEX-3) domain; DENN (after differentially expressed in neoplastic vs normal cells) is a ...
 282-472 3.50e-54

DENN (AEX-3) domain; DENN (after differentially expressed in neoplastic vs normal cells) is a domain which occurs in several proteins involved in Rab- mediated processes or regulation of MAPK signalling pathways.


Pssm-ID: 460461  Cd Length: 186  Bit Score: 187.78  E-value: 3.50e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365  282 FAPKTLVLVSRLDHAEVFRNSLGLIYAIHVEGLN-VCLENVIGNLLTC-TVPLAGGSQldsveegaRTISLGAGDRQVIQ 359
Cdd:pfam02141    1 RIPKAYCIISRLPFFNLFKKFLDELYRRRTISPLpNPIERFIANLLYEvPFPPPGRTQ--------KLKPLGGTEPILLQ 72

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365  360 TPLADSLPVSRCSVALLFRQLGITNVLSLFCAALTEHKVLFLSRSYQRLADACRGLLALLFPLRYSFTYVPILPAQLLEV 439
Cdd:pfam02141   73 RPEDSELPLEGVDLHLLFRCLSPENILQLFEAALLERRIIFLSSDLARLTLVAEAVVALLYPFVWQHIYIPVLPASLLDV 152

                          170       180       190
                   ....*....|....*....|....*....|....
gi 1622837365  440 LSTPTPFIIGVNAAFQAET-QELLDVIVADLDGG 472
Cdd:pfam02141  153 LSAPTPFIIGVHSRYFDLLeDPLDDVVLVDLDTG 186
uDENN pfam03456
uDENN domain; This region is always found associated with pfam02141. It is predicted to form ...
 178-237 3.90e-23

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


Pssm-ID: 460926  Cd Length: 59  Bit Score: 94.21  E-value: 3.90e-23
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365  178 GQILQRFPEKDWEDNPFPQGIELFCQPSGWQLCPERnPPTFFVAVLTDINSERHYCACLT 237
Cdd:pfam03456    1 PEVLDRYPEDDWSDPPLPDGIPMFCFPEGLETLSSR-EPTFFSFVLTDEDGSRLYGACLT 59
uDENN smart00800
Domain always found upstream of DENN domain, found in a variety of signalling proteins; The ...
 159-239 1.03e-22

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.


Pssm-ID: 214824  Cd Length: 89  Bit Score: 93.94  E-value: 1.03e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365   159 GHRLAE-----GQRKRLTGSGEGQ-GQILQRFPEKDWEDNPFPQGIELFCQPSGWQLCP--ERNPPTFFVAVLTDINSER 230
Cdd:smart00800    1 PSRLFDyfvvvGLDSDTGPLGRSYkPEILQRYPEKDFEDFPLPDSIPLFCFPEGLDFVTqtSSKDPQFFSFVLTDIDGSR 80


                    ....*....
gi 1622837365   231 HYCACLTFW 239
Cdd:smart00800   81 RYGFCLRFY 89
dDENN smart00801
Domain always found downstream of DENN domain, found in a variety of signalling proteins; The ...
 526-594 4.05e-19

Domain always found downstream of DENN domain, found in a variety of signalling proteins; The dDENN domain is part of the tripartite DENN domain. It is always found downstream 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.


Pssm-ID: 129037  Cd Length: 69  Bit Score: 83.11  E-value: 4.05e-19
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1622837365   526 DKELRAVFLRLFAQLLQGYRWCLHVVRVHPEPVIRFHKAAFLGQRGLVEDDFLMKVLEGMAFAGFVSER 594
Cdd:smart00801    1 NDEIREAFLRFFVNLFGGYRNFLRELRKEPGPVITFDKESFLKSRPSSERPFLSKFLETQMFSQFIEER 69
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 1952-2053 3.54e-14

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 70.27  E-value: 3.54e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365  1952 YEGTLYKKGA-FMKPWKARWFVLdkTKHQLRYYDHR---VDTECKGVIDLAEVEAVAPGTPTMgapktVDEKAFFDVKT- 2026
Cdd:smart00233    3 KEGWLYKKSGgGKKSWKKRYFVL--FNSTLLYYKSKkdkKSYKPKGSIDLSGCTVREAPDPDS-----SKKPHCFEIKTs 75

                            90       100
                    ....*....|....*....|....*..
gi 1622837365  2027 TRRVYNFCAQDVPSAQQWVDRIQSCLS 2053
Cdd:smart00233   76 DRKTLLLQAESEEEREKWVEALRKAIA 102
GRAM pfam02893
GRAM domain; The GRAM domain is found in in glucosyltransferases, myotubularins and other ...
 1052-1179 3.60e-14

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


Pssm-ID: 397160  Cd Length: 112  Bit Score: 70.47  E-value: 3.60e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1052 LPGEECVLDGLRVYLLPDGReegaggsaggpallPAEGAVFLTTYRVIFTGMPTDPLvgeQVVVrsFPVAALtkeKRISV 1131
Cdd:pfam02893    9 LPPEERLIASYSCYLNRDGG--------------PVQGRLYLTNYRLCFRSLPKGWS---TKVV--IPLVDI---EEIEK 66

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1622837365 1132 QTPVDQLLQDGLQLRSCTFQllKMAFDEEVGSDSAELFRKQLHKLRYP 1179
Cdd:pfam02893   67 LKGGANLFPNGIQVETGSND--KFSFAGFVTRDEAIEFILALLKNAHP 112
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 1952-2053 6.40e-10

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 58.34  E-value: 6.40e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1952 YEGTLYKKG-AFMKPWKARWFVLdkTKHQLRYYDHR---VDTECKGVIDLAEVEAVAPGTPTMGAPKTVdekafFDVKTT 2027
Cdd:pfam00169    3 KEGWLLKKGgGKKKSWKKRYFVL--FDGSLLYYKDDksgKSKEPKGSISLSGCEVVEVVASDSPKRKFC-----FELRTG 75

                           90       100       110
                   ....*....|....*....|....*....|
gi 1622837365 2028 ----RRVYNFCAQDVPSAQQWVDRIQSCLS 2053
Cdd:pfam00169   76 ertgKRTYLLQAESEEERKDWIKAIQSAIR 105
dDENN pfam03455
dDENN domain; This region is always found associated with pfam02141. It is predicted to form a ...
 561-607 5.16e-06

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.


Pssm-ID: 460925  Cd Length: 48  Bit Score: 45.26  E-value: 5.16e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1622837365  561 FHKAAFLGQRGLVEDDFLMKVLEGMAFAGFVSERGVPYRPT-DLFDEL 607
Cdd:pfam03455    1 FDKEAFLKSLPSDSRPFLSQFLETQMFNEFIEERLESSDPSiDLFDEE 48
GRAM smart00568
domain in glucosyltransferases, myotubularins and other putative membrane-associated proteins;
1052-1130 7.03e-06

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


Pssm-ID: 214725 [Multi-domain]  Cd Length: 60  Bit Score: 45.28  E-value: 7.03e-06
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1622837365  1052 LPGEECVLDGLRVYLLPDGreegaggsaggpallPAEGAVFLTTYRVIFTGMPTDPLvgeqvVVRSFPVAALTKEKRIS 1130
Cdd:smart00568    2 LPEEEKLIADYSCYLSRTG---------------PVQGRLYISNYRLCFRSNLPGKL-----TKVVIPLADITRIEKST 60
PHA03247 PHA03247
large tegument protein UL36; Provisional
 34-156 5.20e-03

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 42.23  E-value: 5.20e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365   34 PHPSPPRmeqlSPRKDPsrnravkygPLWSQRARGRQLPLPETFPTVAEDRPEAFPA-----RPRRDRKRSLRGRGQRAT 108
Cdd:PHA03247  2614 PSPLPPD----THAPDP---------PPPSPSPAANEPDPHPPPTVPPPERPRDDPApgrvsRPRRARRLGRAAQASSPP 2680

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1622837365  109 RLFHARGVKDP----DELEHPQLPSDNTEDRPPPLLKALVPPTNQTEPGEAS 156
Cdd:PHA03247  2681 QRPRRRAARPTvgslTSLADPPPPPPTPEPAPHALVSATPLPPGPAAARQAS 2732
 
Name Accession Description Interval E-value
PTP-MTMR5 cd14588
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1312-1684 0e+00

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: 574.22  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1312 FRISPVNRMYAICRSYPGLLIVPQSVQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLLRSGGLHGKGVVGLFKAQNAPSP 1391
Cdd:cd14588      1 FRISTVNRMYAVCRSYPGLLIVPQSIQDNTIQRISRCYRQNRFPVVCWRNSRTKAVLLRSGGLHGKGVVGLFKSQNAPAA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1392 GQSQADSSSLEQEKYLQAVVSSMPRYADASGRNTLSGFssahmgshvpsprarvttlsnpmaasasrrtaprgkwgsvrt 1471
Cdd:cd14588     81 GQSQTDSTSLEQEKYLQAVINSMPRYADASGRNTLSGF------------------------------------------ 118

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1472 sgrssglgtevgsrlagrdtlappqanggppdpgflrpqRAALYILGDKAQLKGVRPDPLQQWELVPIEVFEARQVKASF 1551
Cdd:cd14588    119 ---------------------------------------RAALYIIGDKSQLKGVKQDPLQQWEVVPIEVFDVRQVKASF 159

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1552 KKLLKACVPGCPAAePSPASFLRSLEDSEWLIQIHKLLQVSVLVVELLDSGSSVLVGLEDGWDITTQVVSLVQLLSDPFY 1631
Cdd:cd14588    160 KKLMKACVPSCPST-DPSQTYLRTLEESEWLSQLHKLLQVSVLVVELLDSGSSVLVSLEDGWDITTQVVSLVQLLSDPYY 238

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1622837365 1632 RTLEGFRLLLEKEWLSFGHRFSHRGAHTLAGQSSGFTPVFLQFLDCVHQVHLQ 1684
Cdd:cd14588    239 RTIEGFRLLVEKEWLSFGHRFSHRGAQTLASQSSGFTPVFLQFLDCVHQIHLQ 291
PTP-MTMR5-like cd14534
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1312-1684 1.61e-140

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: 437.95  E-value: 1.61e-140
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1312 FRISPVNRMYAICRSYPGLLIVPQSVQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLLRSGGLHGKGVVGLFKAQNAPSP 1391
Cdd:cd14534      1 FRISTANRDYSICRSYPALVVVPQSVSDESLRKVARCYRQGRFPVVTWRHPRTKALLLRSGGFHGKGVMGMLKSANTSTS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1392 GQ---SQADSSSLEQEKYLQAVVssmpryadasgrntlsgfssahmgshvpsprarvttlsnpmaasasrrtaprgkwgs 1468
Cdd:cd14534     81 SPtvsSSETSSSLEQEKYLSALV--------------------------------------------------------- 103

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1469 vrtsgrssglgtevgsrlagrdtlappqanggppdpgflrpqraaLYILGDKAQLKGVRPDPLQQWELVPIEVFEARQVK 1548
Cdd:cd14534    104 ---------------------------------------------LYVLGEKSQMKGVKAESDPKCEFIPVEYPEVRQVK 138

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1549 ASFKKLLKACVPGCPAAEPSPaSFLRSLEDSEWLIQIHKLLQVSVLVVELLD-SGSSVLVGLEDGWDITTQVVSLVQLLS 1627
Cdd:cd14534    139 ASFKKLLRACVPSSAPTEPEQ-SFLKAVEDSEWLQQLQCLMQLSGAVVDLLDvQGSSVLLCLEDGWDVTTQVSSLSQLLL 217

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1622837365 1628 DPFYRTLEGFRLLLEKEWLSFGHRFSHRGAHTLAGQSSGFTPVFLQFLDCVHQVHLQ 1684
Cdd:cd14534    218 DPYYRTLEGFRVLVEKEWLAFGHRFSHRSNLTAASQSSGFAPVFLQFLDAVHQIHRQ 274
PTP-MTMR13 cd14589
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1312-1684 9.50e-136

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: 425.88  E-value: 9.50e-136
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1312 FRISPVNRMYAICRSYPGLLIVPQSVQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLLRSGGLHGKGVVGLFKAQNAPSP 1391
Cdd:cd14589      1 FRITAVNRMYSLCRSYPGLLVVPQSVQDSSLQKVARCYRHNRLPVVCWKNSKTKAVLLRSGGFHGKGVVGLFKSQNPHSA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1392 GQSQAD-SSSLEQEKYLQAVVSSMPRYADASGRNTLsgfssahmgshvpsprarvttlsnpmaasasrrtaprgkwgsvr 1470
Cdd:cd14589     81 APASSEsSSSIEQEKYLQALLNAISVHQKMNGNSTL-------------------------------------------- 116

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1471 tsgrssglgteVGSRLAGRdtlappqanggppdpgflrpqRAALYILGDKAQLKGVRPDPLQQWELVPIEVFEARQVKAS 1550
Cdd:cd14589    117 -----------LQSQLLKR---------------------QAALYIFGEKSQLRGFKLDFALNCEFVPVEFHDIRQVKAS 164

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1551 FKKLLKACVPGCPAAEPSpASFLRSLEDSEWLIQIHKLLQVSVLVVELLDSGSSVLVGLEDGWDITTQVVSLVQLLSDPF 1630
Cdd:cd14589    165 FKKLMRACVPSTIPTDSE-VTFLKALGESEWFLQLHRIMQLAVVISELLESGSSVMVCLEDGWDITTQVVSLVQLLSDPF 243

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1622837365 1631 YRTLEGFRLLLEKEWLSFGHRFSHRGAHTLAGQSSGFTPVFLQFLDCVHQVHLQ 1684
Cdd:cd14589    244 YRTLEGFQMLVEKEWLSFGHKFSQRSNLTPNSQGSGFAPIFLQFLDCVHQIHNQ 297
SBF2 pfam12335
Myotubularin protein; This domain family is found in eukaryotes, and is approximately 220 ...
 704-926 1.21e-135

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.


Pssm-ID: 463536  Cd Length: 227  Bit Score: 422.11  E-value: 1.21e-135
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365  704 GPPMTAILERCSGLHVNSARRLEVVRNCISYVFEGKMLEAKKLLPAVLRALKGRAARRCLAQELHLHVQQNRAVLDHQQF 783
Cdd:pfam12335    1 GPPVVSIVDKRGNVFSNSARRLEVLRNCISFIFENKISEARKSLPAVLRALKGKAARLALCEELNQHVQQNRAVLDHQQF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365  784 DFVVRMMNCCLQDCTSLDEHGIAAALLPLVTAFCRKLSPGVTQFAYSCVQEHVVWSTPQFWEAMFYGDVQTHIRALYLEP 863
Cdd:pfam12335   81 DLVVRLMNCALQDCSSMDEYGVAAALLPLSTAFCRKLCTGVIQFAYTCVQDHPVWKNQQFWEAAFYQDVQKQIRALYLPS 160

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1622837365  864 TEDLAPAQEVGEAP----SQEDERSALDVASEQRRLWPTLSREKQQELVQKEESTVFSQAIHYANRM 926
Cdd:pfam12335  161 DEKNPHISAQGKNTaslaSHAEEPSALEIAAEQMRLWPTLSKEKQQELVKSEESTVYSQAIHYANRM 227
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
 1290-1719 1.69e-99

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: 323.66  E-value: 1.69e-99
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1290 RDYQRLGLGTlssslsrakSEPFRISPVNRMYAICRSYPGLLIVPQSVQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLL 1369
Cdd:pfam06602   12 AEFARQGLPS---------KDEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHKENGAVIT 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1370 RSgglhgkgvvglfkAQnaPSPGQSQAdsSSLEQEKYLQAVVSSmpryadasgrntlsgfssahmgshvpsprarvttls 1449
Cdd:pfam06602   83 RS-------------SQ--PLVGLNGK--RSIEDEKLLQAIFKS------------------------------------ 109

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1450 npmaasasrrtaprgkwgsvrtsgrssglgtevgsrlagrdtlappqANGGPPDPGFLRPQRAALYILGDKAQLKGVRP- 1528
Cdd:pfam06602  110 -----------------------------------------------SNPYSAKKLYIVDARPKLNAMANRAKGGGYENe 142

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1529 DPLQQWELVPIEVFEARQVKASFKKLLKACVPgcpaAEPSPASFLRSLEDSEWLIQIHKLLQVSVLVVELLDS-GSSVLV 1607
Cdd:pfam06602  143 DNYPNCKKIFLGIENIHVMRDSLNKLVEACND----RSPSMDKWLSRLESSGWLKHIKAILDGACLIAQAVDLeGSSVLV 218

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1608 GLEDGWDITTQVVSLVQLLSDPFYRTLEGFRLLLEKEWLSFGHRFSHRGAHTLAGQSSGFT-PVFLQFLDCVHQVHLQFP 1686
Cdd:pfam06602  219 HCSDGWDRTAQLTSLAQLLLDPYYRTIEGFQVLIEKEWLSFGHKFADRCGHLAGFTDSKERsPVFLQFLDCVWQLLRQFP 298

                          410       420       430
                   ....*....|....*....|....*....|...
gi 1622837365 1687 MEFEFSQFYLKFLGYHHVSRRFRTFLLDSDYER 1719
Cdd:pfam06602  299 CAFEFNERFLIRLLYHLYSCQFGTFLCNSEKER 331
PH-GRAM_MTMR5 cd13340
Myotubularian (MTM) related 5 protein (MTMR5) Pleckstrin Homology-Glucosyltransferases, ...
 1055-1173 6.52e-68

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.


Pssm-ID: 275417  Cd Length: 119  Bit Score: 224.36  E-value: 6.52e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1055 EECVLDGLRVYLLPDGREEGAGGSAGGPALLPAEGAVFLTTYRVIFTGMPTDPLVGEQVVVRSFPVAALTKEKRISVQTP 1134
Cdd:cd13340      1 EECVMDGLRVYLLPDGREEASGGSLGGPPLLPAEGAIFLTTYRVIFKGTPTDPLVGEQVVVRSFPVASLTKEKRISVQAQ 80

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1622837365 1135 VDQLLQDGLQLRSCTFQLLKMAFDEEVGSDSAELFRKQL 1173
Cdd:cd13340     81 MDQFLQEGLQLRSCTFQLLKIAFDEEVASDSAEVFRKHL 119
PH_Sbf1_hMTMR5 cd01235
Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a ...
 1948-2053 4.52e-62

Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a myotubularin-related pseudo-phosphatase. Both Sbf1 and myotubularin interact with the SET domains of Hrx and other epigenetic regulatory proteins, but Sbf1 lacks phosphatase activity due to several amino acid changes in its structurally preserved catalytic pocket. It contains pleckstrin (PH), GEF, and myotubularin homology domains that are thought to be responsible for signaling and growth control. Sbf1 functions as an inhibitor of cellular growth. The N-terminal GEF homology domain serves to inhibit the transforming effects of Sbf1. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269941  Cd Length: 106  Bit Score: 207.18  E-value: 4.52e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1948 ENRSYEGTLYKKGAFMKPWKARWFVLDKTKHQLRYYDHRVDTECKGVIDLAEVEAVAPGTPTMGAPKTVDEKAFFDVKTT 2027
Cdd:cd01235      1 ENRTHEGYLYKRGALLKGWKQRWFVLDSTKHQLRYYESREDTKCKGFIDLAEVESVTPATPIIGAPKRADEGAFFDLKTN 80

                           90       100
                   ....*....|....*....|....*.
gi 1622837365 2028 RRVYNFCAQDVPSAQQWVDRIQSCLS 2053
Cdd:cd01235     81 KRVYNFCAFDAESAQQWIEKIQSCLS 106
DENN smart00799
Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN; The ...
 283-472 3.38e-60

Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN; The DENN domain 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.


Pssm-ID: 214823  Cd Length: 183  Bit Score: 204.74  E-value: 3.38e-60
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365   283 APKTLVLVSRLDHAEVFRNSLGLIYAIHVEGLNVCLENVIgNLLTCTVPLAGGSQldsveegaRTISLGAGDRQVIQTPL 362
Cdd:smart00799    1 APKCICILSRLPFFELFRKILNELYRLLPSSSNLPLELLI-SLLLYPVPPPGGSL--------VLVSLGPGDLIELQRPL 71

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365   363 ADSLPVSRCSVALLFRQLGITNVLSLFCAALTEHKVLFLSRSYQRLADACRGLLALLFPLRYSFTYVPILPAQLLEVLST 442
Cdd:smart00799   72 DSSLPLIDFSLHELFECLGVENILQLFAALLLERRIIFTSSNLSTLSAVIEALLALLYPFVWQHIYIPILPASLLDVLSA 151

                           170       180       190
                    ....*....|....*....|....*....|..
gi 1622837365   443 PTPFIIGVNAAFQAETQELL--DVIVADLDGG 472
Cdd:smart00799  152 PTPFIIGVHSSYFEEVKELPdeDVVVVDLDTG 183
PH-GRAM_MTMR5_MTMR13 cd13208
Myotubularian (MTM) related 5 and 13 proteins (MTMR5 and MTMR13) Pleckstrin ...
 1055-1173 5.23e-59

Myotubularian (MTM) related 5 and 13 proteins (MTMR5 and MTMR13) Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins (PH-GRAM) domain; MTMR5 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. MTMR13 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. Although the majority of the sequences are MTMR 5 and 13, this cd also contains MTM5 nematode sequences.


Pssm-ID: 275396  Cd Length: 120  Bit Score: 198.73  E-value: 5.23e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1055 EECVLDGLRVYLLPDGREEGAGGSAGGPaLLPAEGAVFLTTYRVIFTGMPTDPLVGEQVVVRSFPVAALTKEKRISVQTP 1134
Cdd:cd13208      1 EELVMEGLRVYLLPDGREEGTGGNGGPN-LLPAEGALFLTNYRVIFKGTPCDPLACEQTVVRSFPIASLTKEKKIAVQKL 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1622837365 1135 --VDQLLQDGLQLRSCTFQLLKMAFDEEVGSDSAELFRKQL 1173
Cdd:cd13208     80 ahLDQKLQEGLQLRSATFQLIKVAFDEEVSSEKIEKFRKQL 120
PTP-MTM-like cd14507
protein tyrosine phosphatase-like domain of myotubularins; Myotubularins are a unique subgroup ...
 1352-1680 1.00e-54

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: 190.84  E-value: 1.00e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1352 NRFPVVCWRSGRSKAVLLRSGGLHgkgvVGLFkaqnapspgqsqaDSSSLEQEKYLQAVvssmpryadasgrntlsgfss 1431
Cdd:cd14507      1 GRIPVLSWRHPRNGAVICRSSQPL----VGLT-------------GSRSKEDEKLLNAI--------------------- 42

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1432 ahmgshvpsprarvttlsnpmaasasRRTAPRGKwgsvrtsgrssglgtevgsRLAGRDTlappqanggppdpgflRPQR 1511
Cdd:cd14507     43 --------------------------RKASPSSK-------------------KLYIVDA----------------RPKL 61

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1512 AALyilGDKAQLKGVR-PDPLQQWELVPIEVFEARQVKASFKKLLKACVPGcpaaEPSPASFLRSLEDSEWLIQIHKLLQ 1590
Cdd:cd14507     62 NAV---ANRAKGGGYEnTEYYPNCELEFLNIENIHAMRDSLNKLRDACLSP----NDEESNWLSALESSGWLEHIRLILK 134

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1591 VSVLVVELLDS-GSSVLVGLEDGWDITTQVVSLVQLLSDPFYRTLEGFRLLLEKEWLSFGHRFSHRGAHTLAGQSSG-FT 1668
Cdd:cd14507    135 GAVRVADLLEKeGTSVLVHCSDGWDRTSQLTSLAQLLLDPYYRTIEGFQVLIEKEWLSFGHKFADRCGHGDKNSSDEeRS 214

                          330
                   ....*....|..
gi 1622837365 1669 PVFLQFLDCVHQ 1680
Cdd:cd14507    215 PIFLQFLDCVWQ 226
DENN pfam02141
DENN (AEX-3) domain; DENN (after differentially expressed in neoplastic vs normal cells) is a ...
 282-472 3.50e-54

DENN (AEX-3) domain; DENN (after differentially expressed in neoplastic vs normal cells) is a domain which occurs in several proteins involved in Rab- mediated processes or regulation of MAPK signalling pathways.


Pssm-ID: 460461  Cd Length: 186  Bit Score: 187.78  E-value: 3.50e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365  282 FAPKTLVLVSRLDHAEVFRNSLGLIYAIHVEGLN-VCLENVIGNLLTC-TVPLAGGSQldsveegaRTISLGAGDRQVIQ 359
Cdd:pfam02141    1 RIPKAYCIISRLPFFNLFKKFLDELYRRRTISPLpNPIERFIANLLYEvPFPPPGRTQ--------KLKPLGGTEPILLQ 72

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365  360 TPLADSLPVSRCSVALLFRQLGITNVLSLFCAALTEHKVLFLSRSYQRLADACRGLLALLFPLRYSFTYVPILPAQLLEV 439
Cdd:pfam02141   73 RPEDSELPLEGVDLHLLFRCLSPENILQLFEAALLERRIIFLSSDLARLTLVAEAVVALLYPFVWQHIYIPVLPASLLDV 152

                          170       180       190
                   ....*....|....*....|....*....|....
gi 1622837365  440 LSTPTPFIIGVNAAFQAET-QELLDVIVADLDGG 472
Cdd:pfam02141  153 LSAPTPFIIGVHSRYFDLLeDPLDDVVLVDLDTG 186
PTP-MTMR6-like cd14532
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases ...
 1291-1704 5.24e-53

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: 188.70  E-value: 5.24e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1291 DYQRLGLgtlssslsraKSEPFRISPVNRMYAICRSYPGLLIVPQSVQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLLR 1370
Cdd:cd14532      4 EYTRMGV----------PNDNWTLSDINKDYELCDTYPRELFVPTSASTPVLVGSSKFRSKGRLPVLSYLHKDNQAAICR 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1371 -SGGLHGkgvvglFKAQnapspgqsqadssSLEQEKYLQAVVSSMPryadasgrntlsgfSSAHMgsHVPSPRARVttls 1449
Cdd:cd14532     74 cSQPLSG------FSAR-------------CVEDEQLLQAIRKANP--------------NSKFM--YVVDTRPKI---- 114

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1450 NPMAasasrrtaprgkwgsvrtsGRSSGLGTEvgsrlagrdtlappqanggppdpgflrpqraalyilgDKAQLKGVRpd 1529
Cdd:cd14532    115 NAMA-------------------NKAAGKGYE-------------------------------------NEDNYSNIK-- 136

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1530 plqqWELVPIEVFEArqVKASFKKLLKACvpgcPAAEPSPASFLRSLEDSEWLIQIHKLLQVSVLVVELLDSGSSVLVGL 1609
Cdd:cd14532    137 ----FQFFGIENIHV--MRSSLQKLLEVC----ELKNPSMSAFLSGLESSGWLKHIKAVMDTSVFIAKAVSEGASVLVHC 206

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1610 EDGWDITTQVVSLVQLLSDPFYRTLEGFRLLLEKEWLSFGHRFSHRGAHtLAGQSSGFTPVFLQFLDCVHQVHLQFPMEF 1689
Cdd:cd14532    207 SDGWDRTAQTCSLASLLLDPYYRTIKGFQVLIEKEWLSFGHKFTDRCGH-LQGDAKEVSPVFTQFLDCVWQLMQQFPRAF 285

                          410
                   ....*....|....*
gi 1622837365 1690 EFSQFYLKFLgYHHV 1704
Cdd:cd14532    286 EFNERFLLTL-HDHV 299
PH-GRAM_MTMR13 cd13339
Myotubularian (MTM) related 13 protein Pleckstrin Homology-Glucosyltransferases, Rab-like ...
 1055-1173 6.96e-48

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.


Pssm-ID: 275416  Cd Length: 119  Bit Score: 167.07  E-value: 6.96e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1055 EECVLDGLRVYLLPDGREEGAGGSAGGPALLPAEGAVFLTTYRVIFTGMPTDPLVGEQVVVRSFPVAALTKEKRISVQTP 1134
Cdd:cd13339      1 EEFVCEGLRVLLDPDGREEATGGLLGGPHILPAEGALFLTTYRIIFKGTPHDQLVGEQTVIRSFPIASITKEKKITIQNQ 80

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1622837365 1135 VDQLLQDGLQLRSCTFQLLKMAFDEEVGSDSAELFRKQL 1173
Cdd:cd13339     81 LQQNMQEGLQITSASFQLIKVAFDEEVSPEVVEIFKKQL 119
PTP-MTMR7 cd14583
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1291-1704 2.85e-41

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: 155.12  E-value: 2.85e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1291 DYQRLGLgtlssslsraKSEPFRISPVNRMYAICRSYPGLLIVPQSVQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLLR 1370
Cdd:cd14583      4 EYNRMGL----------PNSLWQVSDVNRDYRVCDTYPTELYVPKSATAPIIVGSSKFRSRGRFPVLSYYCKDNNASICR 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1371 SgglhgkgvvglfkaqNAPSPGQSqadSSSLEQEKYLQAVVSSMPryadasgrntlsgfSSAHMgsHVPSPRARVTTLSN 1450
Cdd:cd14583     74 S---------------SQPLSGFS---ARCLEDEQMLQAIRKANP--------------GSDFM--YVVDTRPKLNAMAN 119

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1451 pmaasasrrtaprgkwgsvrtsgRSSGLGTEvgsrlaGRDTLAppqanggppdpgflrpqraalyilGDKAQLKGVRPdp 1530
Cdd:cd14583    120 -----------------------RAAGKGYE------NEDNYS------------------------NIKFQFIGIEN-- 144

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1531 lqqwelvpIEVfearqVKASFKKLLKACvpgcPAAEPSPASFLRSLEDSEWLIQIHKLLQVSVLVVELL-DSGSSVLVGL 1609
Cdd:cd14583    145 --------IHV-----MRNSLQKMLEVC----ELRSPSMGDFLWGLENSGWLKHIKAIMDAGIFIAKAVaEEGASVLVHC 207

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1610 EDGWDITTQVVSLVQLLSDPFYRTLEGFRLLLEKEWLSFGHRFSHRGAHtLAGQSSGFTPVFLQFLDCVHQVHLQFPMEF 1689
Cdd:cd14583    208 SDGWDRTAQVCSVASLLLDPYYRTIKGFMVLIEKDWVSFGHKFNHRYGH-LDGDPKEVSPVIDQFIECVWQLMEQFPCAF 286

                          410
                   ....*....|....*
gi 1622837365 1690 EFSQFYLKFLgYHHV 1704
Cdd:cd14583    287 EFNERFLIHI-HHHI 300
PTP-MTMR3 cd14586
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1312-1680 3.89e-41

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: 155.18  E-value: 3.89e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1312 FRISPVNRMYAICRSYPGLLIVPQSVQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLLRSGglhgKGVVGLFKAQNApsp 1391
Cdd:cd14586      8 WRISNINEKYKLCGSYPQELIVPAWITDKELESVASFRSWKRIPAVVYRHQSNGAVIARCG----QPEVSWWGWRNA--- 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1392 gqsqadssslEQEKYLQAVVSSmpryadasgrntlsgfssahmgshvpsprarvttlsnpmAASASRRTAPRGKWGSVRT 1471
Cdd:cd14586     81 ----------DDEHLVQSVAKA---------------------------------------CASDSSSCKSVLMTGNCSR 111

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1472 SGRSSGLGTEVGSRlAGRDTLAPPQANGGPPDPGFLRPQRAALYILGDKAQLKGVR-PDPLQQWELVPIEVFEARQVKAS 1550
Cdd:cd14586    112 DFPNGGDLSDVEFD-SSMSNASGVESLAIQPQKLLILDARSYAAAVANRAKGGGCEcPEYYPNCEVVFMGMANIHSIRKS 190

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1551 FKKLLKACvpgcpAAEPSPASFLRSLEDSEWLIQIHKLLQVSVLVVELLDSGSS-VLVGLEDGWDITTQVVSLVQLLSDP 1629
Cdd:cd14586    191 FQSLRLLC-----TQMPDPANWLSALESTKWLQHLSMLLKSALLVVHAVDRDQRpVLVHCSDGWDRTPQIVALSKLLLDP 265

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1622837365 1630 FYRTLEGFRLLLEKEWLSFGHRFSHRGAHtlaGQSSG----FTPVFLQFLDCVHQ 1680
Cdd:cd14586    266 YYRTIEGFQVLVETEWLDFGHKFADRCGH---GENSDdlneRCPVFLQWLDCVHQ 317
PTP-MTMR8 cd14584
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1291-1696 7.69e-40

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: 151.18  E-value: 7.69e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1291 DYQRLGLgtlssslsraKSEPFRISPVNRMYAICRSYPGLLIVPQSVQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLLR 1370
Cdd:cd14584     10 DFQRMGI----------PNDYWEITDANKNYEICSTYPPELVVPKSASKATVVGSSKFRSRGRFPVLSYLYKENNAAICR 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1371 SgglhgkgvvglfkaqNAPSPGQSqadSSSLEQEKYLQAVVSSMPryadasgrntlsgfSSAHMgsHVPSPRARVTTLSN 1450
Cdd:cd14584     80 C---------------SQPLSGFS---ARCVEDEQMLQAISKANP--------------GSPFM--YVVDTRPKLNAMAN 125

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1451 pmaasasrrtaprgkwgsvrtsgRSSGLGTEvgsrlagrdtlappqanggppdpgflrpqraalyilgDKAQLKGVRpdp 1530
Cdd:cd14584    126 -----------------------RAAGKGYE-------------------------------------NEDNYSNIR--- 142

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1531 lqqWELVPIEVFEArqVKASFKKLLKACvpgcPAAEPSPASFLRSLEDSEWLIQIHKLLQVSVLVVELL-DSGSSVLVGL 1609
Cdd:cd14584    143 ---FQFIGIENIHV--MRSSLQKLLEVC----EMKSPSMSDFLTGLENSGWLRHIKAVMDAGVFLAKAVkEEKASVLVHC 213

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1610 EDGWDITTQVVSLVQLLSDPFYRTLEGFRLLLEKEWLSFGHRFSHRGAHtLAGQSSGFTPVFLQFLDCVHQVHLQFPMEF 1689
Cdd:cd14584    214 SDGWDRTAQVCSLASLLLDPFYRTIKGLMVLIEKEWISMGHKFSQRCGH-LDGDPKEVSPVFTQFLECVWQLMEQFPCAF 292


                   ....*..
gi 1622837365 1690 EFSQFYL 1696
Cdd:cd14584    293 EFNEHFL 299
PTP-MTMR4 cd14587
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1312-1680 1.18e-39

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: 150.57  E-value: 1.18e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1312 FRISPVNRMYAICRSYPGLLIVPQSVQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLLRSgglhgkgvvglfkaqnapsp 1391
Cdd:cd14587      3 WRVSEINSNYKLCSSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLRNGAVIARC-------------------- 62

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1392 gqsqadsssleqekylqavvsSMPRYADASGRNTLSGFssahmgshvpspraRVTTLSNPMAASASRRtAPRGKWGSVRT 1471
Cdd:cd14587     63 ---------------------SQPEISWWGWRNADDEY--------------LVTSIAKACALDPGTR-APGGSPSKGNS 106

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1472 SGrSSGLGTEVGSRLagrdTLAPPQANGGPPDPGFLRPQRAALYILGDKAQLKGVRPDPL-QQWELVPIEVFEARQVKAS 1550
Cdd:cd14587    107 DG-SDASDTDFDSSL----TACSAVESGAAPQKLLILDARSYTAAVANRAKGGGCECEEYyPNCEVMFMGMANIHSIRNS 181

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1551 FKKLLKACvpgcpAAEPSPASFLRSLEDSEWLIQIHKLLQVSVLVVELLD-SGSSVLVGLEDGWDITTQVVSLVQLLSDP 1629
Cdd:cd14587    182 FQYLRAVC-----SQMPDPGNWLSALESTKWLQHLSVMLKAAVLVASAVDrEGRPVLVHCSDGWDRTPQIVALAKILLDP 256

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1622837365 1630 FYRTLEGFRLLLEKEWLSFGHRFSHRGAHTLAGQS-SGFTPVFLQFLDCVHQ 1680
Cdd:cd14587    257 YYRTIEGFQVLVETDWLDFGHKFGDRCGHQENVEDqNEQCPVFLQWLDCVHQ 308
PTP-MTM1-like cd14535
protein tyrosine phosphatase-like domain of myotubularin, and myotubularin related ...
 1529-1696 6.82e-38

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: 143.36  E-value: 6.82e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1529 DPLQQWELVPIEVFEARQVKASFKKLLKACVPGCPAAEpspasFLRSLEDSEWLIQIHKLLQVSVLVVELLDSG-SSVLV 1607
Cdd:cd14535     77 DAYQNAELVFLDIHNIHVMRESLRKLKDICFPNIDDSH-----WLSNLESTHWLEHIKLILAGAVRIADKVESGkTSVVV 151

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1608 GLEDGWDITTQVVSLVQLLSDPFYRTLEGFRLLLEKEWLSFGHRFSHRGAHTLAGQS-SGFTPVFLQFLDCVHQVHLQFP 1686
Cdd:cd14535    152 HCSDGWDRTAQLTSLAMLMLDPYYRTIRGFEVLIEKEWLSFGHKFAQRIGHGDKNHSdADRSPVFLQFIDCVWQMTRQFP 231

                          170
                   ....*....|
gi 1622837365 1687 MEFEFSQFYL 1696
Cdd:cd14535    232 NAFEFNEHFL 241
PTP-MTMR6 cd14585
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1291-1696 1.14e-37

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: 144.69  E-value: 1.14e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1291 DYQRLGLgtlssslsraKSEPFRISPVNRMYAICRSYPGLLIVPQSVQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLLR 1370
Cdd:cd14585      4 EYKRMGV----------PNDYWQLSDVNRDYKICDTYPRDLYVPITASKPIIVGSSKFRSKGRFPVLSYYHQEKKAAICR 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1371 -SGGLHGkgvvglFKAQnapspgqsqadssSLEQEKYLQAVVSSMPryadasgrntlsgfSSAHMgsHVPSPRARVTTLS 1449
Cdd:cd14585     74 cSQPLSG------FSAR-------------CLEDEHMLQAISKANP--------------NNRYM--YVMDTRPKLNAMA 118

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1450 NpmaasasrrtaprgkwgsvrtsgRSSGLGTEvgsrlagrdtlappqanggppdpgflrpqraalyilgDKAQLKGVRpd 1529
Cdd:cd14585    119 N-----------------------RAAGKGYE-------------------------------------NEDNYSNIR-- 136

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1530 plqqWELVPIEVFEArqVKASFKKLLKACvpGCPAAepSPASFLRSLEDSEWLIQIHKLLQVSVLVVELL-DSGSSVLVG 1608
Cdd:cd14585    137 ----FQFVGIENIHV--MRSSLQKLLEVC--GTKAL--SVNDFLSGLESSGWLRHIKAVLDAAVFLAKAVaVEGASVLVH 206

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1609 LEDGWDITTQVVSLVQLLSDPFYRTLEGFRLLLEKEWLSFGHRFSHRGAHtLAGQSSGFTPVFLQFLDCVHQVHLQFPME 1688
Cdd:cd14585    207 CSDGWDRTAQVCSLGSLLLDPYYRTIKGFMVLIEKDWISFGHKFSDRCGQ-LDGDPKEISPVFTQFLECVWQLTEQFPRA 285


                   ....*...
gi 1622837365 1689 FEFSQFYL 1696
Cdd:cd14585    286 FEFSEAFL 293
PTP-MTMR3-like cd14533
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases ...
 1547-1680 4.33e-36

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: 137.54  E-value: 4.33e-36
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1547 VKASFKKLLKACvpgcpAAEPSPASFLRSLEDSEWLIQIHKLLQVSVLVVELLD-SGSSVLVGLEDGWDITTQVVSLVQL 1625
Cdd:cd14533     99 IRKSFHSLRALC-----SSAPDQPNWLSNLESTKWLHHLSGLLKAALLVVNAVDeEGRPVLVHCSDGWDRTPQIVALAEL 173

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1622837365 1626 LSDPFYRTLEGFRLLLEKEWLSFGHRFSHRGAHTL-AGQSSGFTPVFLQFLDCVHQ 1680
Cdd:cd14533    174 MLDPYYRTIEGFQVLVEREWLDFGHKFADRCGHGVnSEDINERCPVFLQWLDCVHQ 229
PTP-MTMR2 cd14590
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1506-1696 2.45e-35

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: 136.70  E-value: 2.45e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1506 FLRPQRAALYILGDKAQLKGVRP-DPLQQWELVPIEVFEARQVKASFKKLLKACVPGCpaaepSPASFLRSLEDSEWLIQ 1584
Cdd:cd14590     66 FIFDARPSVNAVANKAKGGGYESeDAYQNAELVFLDIHNIHVMRESLRKLKEIVYPNI-----EESHWLSNLESTHWLEH 140

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1585 IHKLLQVSVLVVELLDSG-SSVLVGLEDGWDITTQVVSLVQLLSDPFYRTLEGFRLLLEKEWLSFGHRFSHRGAHTLAGQ 1663
Cdd:cd14590    141 IKLILAGALRIADKVESGkTSVVVHCSDGWDRTAQLTSLAMLMLDGYYRTIRGFEVLVEKEWLSFGHRFQLRVGHGDKNH 220

                          170       180       190
                   ....*....|....*....|....*....|....
gi 1622837365 1664 S-SGFTPVFLQFLDCVHQVHLQFPMEFEFSQFYL 1696
Cdd:cd14590    221 AdADRSPVFLQFIDCVWQMTRQFPTAFEFNEYFL 254
PTP-MTM1 cd14591
protein tyrosine phosphatase-like domain of myotubularin phosphoinositide phosphatase 1; ...
 1529-1696 3.26e-35

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: 135.54  E-value: 3.26e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1529 DPLQQWELVPIEVFEARQVKASFKKLlKACVpgCPAAEPSpaSFLRSLEDSEWLIQIHKLLQVSVLVVELLDSG-SSVLV 1607
Cdd:cd14591     77 DAYQNAELVFLDIHNIHVMRESLKKL-KDIV--YPNVEES--HWLSSLESTHWLEHIKLVLTGAIQVADKVSSGkSSVLV 151

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1608 GLEDGWDITTQVVSLVQLLSDPFYRTLEGFRLLLEKEWLSFGHRFSHRGAHTLAGQS-SGFTPVFLQFLDCVHQVHLQFP 1686
Cdd:cd14591    152 HCSDGWDRTAQLTSLAMLMLDSYYRTIEGFEVLVQKEWISFGHKFASRIGHGDKNHAdADRSPIFLQFIDCVWQMSKQFP 231

                          170
                   ....*....|
gi 1622837365 1687 MEFEFSQFYL 1696
Cdd:cd14591    232 TAFEFNEQFL 241
PTP-MTM-like_fungal cd17666
protein tyrosine phosphatase-like domain of fungal myotubularins; Myotubularins are a unique ...
 1564-1680 8.70e-34

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: 131.03  E-value: 8.70e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1564 AAEPSPASFLRSLEDSEWLIQIHKLLQVSVLVVELLD-SGSSVLVGLEDGWDITTQVVSLVQLLSDPFYRTLEGFRLLLE 1642
Cdd:cd17666    118 DSNPSYPPLINALKKSNWLKYLAIILQGADLIAKSIHfNHSHVLIHCSDGWDRTSQLSALAQLCLDPYYRTLEGFMVLVE 197

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1622837365 1643 KEWLSFGHRFSHRGAHTLAgqssgfTPVFLQFLDCVHQ 1680
Cdd:cd17666    198 KDWLSFGHRFAERSGHKET------SPVFHQFLDCVYQ 229
PTP-MTMR1 cd14592
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1535-1696 9.16e-34

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: 131.64  E-value: 9.16e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1535 ELVPIEVFEARQVKASFKKLLKACVPGCpaaepSPASFLRSLEDSEWLIQIHKLLQVSVLVVELLDSG-SSVLVGLEDGW 1613
Cdd:cd14592     83 ELVFLEIHNIHVMRESLRKLKEIVYPSI-----DEARWLSNVDGTHWLEYIRMLLAGAVRIADKIESGkTSVVVHCSDGW 157

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1614 DITTQVVSLVQLLSDPFYRTLEGFRLLLEKEWLSFGHRFSHRGAHTLAGQS-SGFTPVFLQFLDCVHQVHLQFPMEFEFS 1692
Cdd:cd14592    158 DRTAQLTSLAMLMLDSYYRTIKGFEVLIEKEWISFGHRFALRVGHGDDNHAdADRSPIFLQFIDCVWQMTRQFPSAFEFN 237


                   ....
gi 1622837365 1693 QFYL 1696
Cdd:cd14592    238 ELFL 241
PTP-MTMR9 cd14536
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1533-1680 1.78e-25

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: 106.65  E-value: 1.78e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1533 QWELV--PIEVFEARQvkASFKKLLKACV-PGCpaaepSPASFLRSLEDSEWLIQIHKLLQVSVLVVELLDS-GSSVLVG 1608
Cdd:cd14536     78 QWRRIhkPIERYNVLQ--ESLIKLVEACNdQGH-----SMDKWLSKLESSNWLSHVKEILTTACLVAQCIDReGASVLVH 150

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1622837365 1609 LEDGWDITTQVVSLVQLLSDPFYRTLEGFRLLLEKEWLSFGHRFSHRGAHTLAGQSSGFT--PVFLQFLDCVHQ 1680
Cdd:cd14536    151 GSEGMDSTLQVTSLAQIILDPDCRTIRGFEALIEREWLQAGHPFQSRCAKSAYSNSKQKFesPVFLLFLDCVWQ 224
PTP-MTMR10-like cd14537
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1544-1680 2.03e-25

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: 105.89  E-value: 2.03e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1544 ARQVKASFKKLLKACVPGCPAAEPSPAS-FLRSLEDSEWLIQIHKLLQVSVLVVELL-DSGSSVLVGLEDGWDITTQVVS 1621
Cdd:cd14537     61 LQDVQAAYLKLRELCTPDSSEQFWVQDSkWYSLLENTKWLHYVSACLKKASEAAEALeSRGRSVVLQESDGRDLSCVVSS 140

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1622 LVQLLSDPFYRTLEGFRLLLEKEWLSFGHRFSHRGAHTLAGQ-SSGFTPVFLQFLDCVHQ 1680
Cdd:cd14537    141 LVQLLLDPHFRTITGFQSLIQKEWVALGHPFCDRLGHVKPNKtESEESPVFLLFLDCVWQ 200
uDENN pfam03456
uDENN domain; This region is always found associated with pfam02141. It is predicted to form ...
 178-237 3.90e-23

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


Pssm-ID: 460926  Cd Length: 59  Bit Score: 94.21  E-value: 3.90e-23
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365  178 GQILQRFPEKDWEDNPFPQGIELFCQPSGWQLCPERnPPTFFVAVLTDINSERHYCACLT 237
Cdd:pfam03456    1 PEVLDRYPEDDWSDPPLPDGIPMFCFPEGLETLSSR-EPTFFSFVLTDEDGSRLYGACLT 59
uDENN smart00800
Domain always found upstream of DENN domain, found in a variety of signalling proteins; The ...
 159-239 1.03e-22

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.


Pssm-ID: 214824  Cd Length: 89  Bit Score: 93.94  E-value: 1.03e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365   159 GHRLAE-----GQRKRLTGSGEGQ-GQILQRFPEKDWEDNPFPQGIELFCQPSGWQLCP--ERNPPTFFVAVLTDINSER 230
Cdd:smart00800    1 PSRLFDyfvvvGLDSDTGPLGRSYkPEILQRYPEKDFEDFPLPDSIPLFCFPEGLDFVTqtSSKDPQFFSFVLTDIDGSR 80


                    ....*....
gi 1622837365   231 HYCACLTFW 239
Cdd:smart00800   81 RYGFCLRFY 89
PTP-MTMR10 cd14593
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1545-1680 3.16e-21

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: 93.42  E-value: 3.16e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1545 RQVKASFKKLLKACVPgcPAAEPSPASFLRSLEDSEWLIQIHKLLQVSVLVVELLDSGS-SVLVGLEDGWDITTQVVSLV 1623
Cdd:cd14593     62 QEIQAAFVKLKQLCVN--EPFEETEEKWLSSLESTRWLEYVRAFLKHSAELVYMLESKHvSVILQEEEGRDLSCVVASLV 139

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1622837365 1624 QLLSDPFYRTLEGFRLLLEKEWLSFGHRFSHRGAHtLAGQSSGFTPVFLQFLDCVHQ 1680
Cdd:cd14593    140 QVMLDPYFRTITGFQSLIQKEWVMAGYRFLDRCNH-LKKSSKKESPLFLLFLDCVWQ 195
PTP-MTMR12 cd14594
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1573-1681 1.97e-20

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: 91.44  E-value: 1.97e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1573 LRSLEDSEWLIQIHKLLQVSVLVVELLDS-GSSVLVGLEDGWDITTQVVSLVQLLSDPFYRTLEGFRLLLEKEWLSFGHR 1651
Cdd:cd14594     95 FSSLESSNWLEIIRQCLKKAVEVVECLEKqNTNVLLTEEEATDLCCVISSLVQIMMDPYCRTKSGFQSLIQKEWVMGGHC 174

                           90       100       110
                   ....*....|....*....|....*....|
gi 1622837365 1652 FSHRGAHtLAGQSSGFTPVFLQFLDCVHQV 1681
Cdd:cd14594    175 FLDRCNH-LRQNDKEEVPVFLLFLDCVWQL 203
dDENN smart00801
Domain always found downstream of DENN domain, found in a variety of signalling proteins; The ...
 526-594 4.05e-19

Domain always found downstream of DENN domain, found in a variety of signalling proteins; The dDENN domain is part of the tripartite DENN domain. It is always found downstream 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.


Pssm-ID: 129037  Cd Length: 69  Bit Score: 83.11  E-value: 4.05e-19
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1622837365   526 DKELRAVFLRLFAQLLQGYRWCLHVVRVHPEPVIRFHKAAFLGQRGLVEDDFLMKVLEGMAFAGFVSER 594
Cdd:smart00801    1 NDEIREAFLRFFVNLFGGYRNFLRELRKEPGPVITFDKESFLKSRPSSERPFLSKFLETQMFSQFIEER 69
PTP-MTMR11 cd14595
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1547-1681 5.35e-18

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: 84.11  E-value: 5.35e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1547 VKASFKKLLKACVPGCPAAEPSPASFLrSLEDSEWLIQIHKLLQVSVLVVELLDSGS-SVLVGLEDGWDITTQVVSLVQL 1625
Cdd:cd14595     62 IQLAYLKLRTLCLPDISVSVSDEKWLS-NLEGTRWLDHVRACLRKASEVSCLLAERHrSVILQESEDRDLNCLLSSLVQL 140

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1622837365 1626 LSDPFYRTLEGFRLLLEKEWLSFGHRFSHRgAHTLAGQSSGFTPVFLQFLDCVHQV 1681
Cdd:cd14595    141 LSDPHARTISGFQSLVQKEWVVAGHPFLQR-LNLTRESDKEESPVFLLFLDCVWQL 195
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 1952-2053 3.54e-14

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 70.27  E-value: 3.54e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365  1952 YEGTLYKKGA-FMKPWKARWFVLdkTKHQLRYYDHR---VDTECKGVIDLAEVEAVAPGTPTMgapktVDEKAFFDVKT- 2026
Cdd:smart00233    3 KEGWLYKKSGgGKKSWKKRYFVL--FNSTLLYYKSKkdkKSYKPKGSIDLSGCTVREAPDPDS-----SKKPHCFEIKTs 75

                            90       100
                    ....*....|....*....|....*..
gi 1622837365  2027 TRRVYNFCAQDVPSAQQWVDRIQSCLS 2053
Cdd:smart00233   76 DRKTLLLQAESEEEREKWVEALRKAIA 102
GRAM pfam02893
GRAM domain; The GRAM domain is found in in glucosyltransferases, myotubularins and other ...
 1052-1179 3.60e-14

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


Pssm-ID: 397160  Cd Length: 112  Bit Score: 70.47  E-value: 3.60e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1052 LPGEECVLDGLRVYLLPDGReegaggsaggpallPAEGAVFLTTYRVIFTGMPTDPLvgeQVVVrsFPVAALtkeKRISV 1131
Cdd:pfam02893    9 LPPEERLIASYSCYLNRDGG--------------PVQGRLYLTNYRLCFRSLPKGWS---TKVV--IPLVDI---EEIEK 66

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1622837365 1132 QTPVDQLLQDGLQLRSCTFQllKMAFDEEVGSDSAELFRKQLHKLRYP 1179
Cdd:pfam02893   67 LKGGANLFPNGIQVETGSND--KFSFAGFVTRDEAIEFILALLKNAHP 112
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
 1951-2052 4.48e-13

Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; DAPP1 (also known as PHISH/3' phosphoinositide-interacting SH2 domain-containing protein or Bam32) plays a role in B-cell activation and has potential roles in T-cell and mast cell function. DAPP1 promotes B cell receptor (BCR) induced activation of Rho GTPases Rac1 and Cdc42, which feed into mitogen-activated protein kinases (MAPK) activation pathways and affect cytoskeletal rearrangement. DAPP1can also regulate BCR-induced activation of extracellular signal-regulated kinase (ERK), and c-jun NH2-terminal kinase (JNK). DAPP1 contains an N-terminal SH2 domain and a C-terminal pleckstrin homology (PH) domain with a single tyrosine phosphorylation site located centrally. DAPP1 binds strongly to both PtdIns(3,4,5)P3 and PtdIns(3,4)P2. The PH domain is essential for plasma membrane recruitment of PI3K upon cell activation. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269977 [Multi-domain]  Cd Length: 96  Bit Score: 66.96  E-value: 4.48e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1951 SYEGTLYKKGAFMKPWKARWFVLdkTKHQLRYYDHRVDTECKGVIDLAEVEAVapgtptmgAPKTVDEKAF-FDVKTTRR 2029
Cdd:cd10573      4 SKEGYLTKLGGIVKNWKTRWFVL--RRNELKYFKTRGDTKPIRVLDLRECSSV--------QRDYSQGKVNcFCLVFPER 73

                           90       100
                   ....*....|....*....|...
gi 1622837365 2030 VYNFCAQDVPSAQQWVDRIQSCL 2052
Cdd:cd10573     74 TFYMYANTEEEADEWVKLLKWKL 96
PH_SWAP-70 cd13273
Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called ...
 1953-2052 4.94e-12

Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called Differentially expressed in FDCP 6/DEF-6 or IRF4-binding protein) functions in cellular signal transduction pathways (in conjunction with Rac), regulates cell motility through actin rearrangement, and contributes to the transformation and invasion activity of mouse embryo fibroblasts. Metazoan SWAP-70 is found in B lymphocytes, mast cells, and in a variety of organs. Metazoan SWAP-70 contains an N-terminal EF-hand motif, a centrally located PH domain, and a C-terminal coiled-coil domain. The PH domain of Metazoan SWAP-70 contains a phosphoinositide-binding site and a nuclear localization signal (NLS), which localize SWAP-70 to the plasma membrane and nucleus, respectively. The NLS is a sequence of four Lys residues located at the N-terminus of the C-terminal a-helix; this is a unique characteristic of the Metazoan SWAP-70 PH domain. The SWAP-70 PH domain binds PtdIns(3,4,5)P3 and PtdIns(4,5)P2 embedded in lipid bilayer vesicles. There are additional plant SWAP70 proteins, but these are not included in this hierarchy. Rice SWAP70 (OsSWAP70) exhibits GEF activity toward the its Rho GTPase, OsRac1, and regulates chitin-induced production of reactive oxygen species and defense gene expression in rice. Arabidopsis SWAP70 (AtSWAP70) plays a role in both PAMP- and effector-triggered immunity. Plant SWAP70 contains both DH and PH domains, but their arrangement is the reverse of that in typical DH-PH-type Rho GEFs, wherein the DH domain is flanked by a C-terminal PH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270092  Cd Length: 110  Bit Score: 64.24  E-value: 4.94e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1953 EGTLYKKGAFMKPWKARWFVLdkTKHQLRYYDHRVDTECKGVIDLAE---VEavapgtptmGAPKTVDEKAFFDVKTTRR 2029
Cdd:cd13273     11 KGYLWKKGHLLPTWTERWFVL--KPNSLSYYKSEDLKEKKGEIALDSnccVE---------SLPDREGKKCRFLVKTPDK 79

                           90       100
                   ....*....|....*....|...
gi 1622837365 2030 VYNFCAQDVPSAQQWVDRIQSCL 2052
Cdd:cd13273     80 TYELSASDHKTRQEWIAAIQTAI 102
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
 1954-2048 1.96e-11

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270110  Cd Length: 106  Bit Score: 62.64  E-value: 1.96e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1954 GTLYKKGAFMKPWKARWFVLdkTKHQLRYYDHRVDTECKGVIDLAEVEAVAPgtptmgAPKTVDEKAFFdVKTTRRVYNF 2033
Cdd:cd13298     10 GYLLKRSRKTKNWKKRWVVL--RPCQLSYYKDEKEYKLRRVINLSELLAVAP------LKDKKRKNVFG-IYTPSKNLHF 80

                           90
                   ....*....|....*
gi 1622837365 2034 CAQDVPSAQQWVDRI 2048
Cdd:cd13298     81 RATSEKDANEWVEAL 95
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 1952-2048 2.29e-11

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275388 [Multi-domain]  Cd Length: 92  Bit Score: 61.79  E-value: 2.29e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1952 YEGTLYKKGAF-MKPWKARWFVLDktKHQLRYY--DHRVDTECKGVIDLAEVEAVAPGTPTmgapktvDEKAFFDVKTT- 2027
Cdd:cd00821      1 KEGYLLKRGGGgLKSWKKRWFVLF--EGVLLYYksKKDSSYKPKGSIPLSGILEVEEVSPK-------ERPHCFELVTPd 71

                           90       100
                   ....*....|....*....|.
gi 1622837365 2028 RRVYNFCAQDVPSAQQWVDRI 2048
Cdd:cd00821     72 GRTYYLQADSEEERQEWLKAL 92
PH_TBC1D2A cd01265
TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1 ...
 1952-2050 3.62e-11

TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1/Prostate antigen recognized and identified by SEREX 1 and ARMUS) contains a PH domain and a TBC-type GTPase catalytic domain. TBC1D2A integrates signaling between Arf6, Rac1, and Rab7 during junction disassembly. Activated Rac1 recruits TBC1D2A to locally inactivate Rab7 via its C-terminal TBC/RabGAP domain and facilitate E-cadherin degradation in lysosomes. The TBC1D2A PH domain mediates localization at cell-cell contacts and coprecipitates with cadherin complexes. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269966  Cd Length: 102  Bit Score: 61.57  E-value: 3.62e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1952 YEGTLYKKGAFMKPWKARWFVLDKTKHQLRYYDHRVDTECKGVIDLAeveavapgtptmGAPKTVD---EKAFFDVKTTR 2028
Cdd:cd01265      5 YLNKLETRGLGLKGWKRRWFVLDESKCQLYYYRSPQDATPLGSIDLS------------GAAFSYDpeaEPGQFEIHTPG 72

                           90       100
                   ....*....|....*....|..
gi 1622837365 2029 RVYNFCAQDVPSAQQWVDRIQS 2050
Cdd:cd01265     73 RVHILKASTRQAMLYWLQALQS 94
PH_PHLDB1_2 cd14673
Pleckstrin homology-like domain-containing family B member 2 pleckstrin homology (PH) domain; ...
 1950-2048 2.14e-10

Pleckstrin homology-like domain-containing family B member 2 pleckstrin homology (PH) domain; PHLDB2 (also called LL5beta) and PHLDB1 (also called LL5alpha) are cytoskeleton- and membrane-associated proteins. PHLDB2 has been identified as a key component of the synaptic podosomes that play an important role in in postsynaptic maturation. Both are large proteins containing an N-terminal pleckstrin (PH) domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270192  Cd Length: 105  Bit Score: 59.51  E-value: 2.14e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1950 RSYEGTLYKKGAFMKPWKARWFVLDKTKHQLRYYDHRVDTECKGVIDLAEVEAVAPGTpTMGAPKTVDEKAFFDVKTTRR 2029
Cdd:cd14673      3 KRCRGFLTKMGGKIKTWKKRWFVFDRNKRTLSYYVDKHEKKLKGVIYFQAIEEVYYDH-LRSAAKSPNPALTFCVKTHDR 81

                           90
                   ....*....|....*....
gi 1622837365 2030 VYNFCAQDVPSAQQWVDRI 2048
Cdd:cd14673     82 LYYMVAPSPEAMRIWMDVI 100
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
 1953-2054 2.88e-10

ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, repeat 1; ARAP proteins (also called centaurin delta) are phosphatidylinositol 3,4,5-trisphosphate-dependent GTPase-activating proteins that modulate actin cytoskeleton remodeling by regulating ARF and RHO family members. They bind phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P3) and phosphatidylinositol 3,4-bisphosphate (PtdIns(3,4,5)P2) binding. There are 3 mammalian ARAP proteins: ARAP1, ARAP2, and ARAP3. All ARAP proteins contain a N-terminal SAM (sterile alpha motif) domain, 5 PH domains, an ArfGAP domain, 2 ankyrin domain, A RhoGap domain, and a Ras-associating domain. This hierarchy contains the first PH domain in ARAP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270073  Cd Length: 94  Bit Score: 58.94  E-value: 2.88e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1953 EGTLYKKG--AFMKPWKARWFVLDKTkhQLRYYDHRVDTECKGVIDLAEVEAV-APGtptmgapktvDEKafFDVKTTRR 2029
Cdd:cd13253      3 SGYLDKQGgqGNNKGFQKRWVVFDGL--SLRYFDSEKDAYSKRIIPLSAISTVrAVG----------DNK--FELVTTNR 68

                           90       100
                   ....*....|....*....|....*
gi 1622837365 2030 VYNFCAQDVPSAQQWVDRIQSCLSD 2054
Cdd:cd13253     69 TFVFRAESDDERNLWCSTLQAAISE 93
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 1952-2053 6.40e-10

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 58.34  E-value: 6.40e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1952 YEGTLYKKG-AFMKPWKARWFVLdkTKHQLRYYDHR---VDTECKGVIDLAEVEAVAPGTPTMGAPKTVdekafFDVKTT 2027
Cdd:pfam00169    3 KEGWLLKKGgGKKKSWKKRYFVL--FDGSLLYYKDDksgKSKEPKGSISLSGCEVVEVVASDSPKRKFC-----FELRTG 75

                           90       100       110
                   ....*....|....*....|....*....|
gi 1622837365 2028 ----RRVYNFCAQDVPSAQQWVDRIQSCLS 2053
Cdd:pfam00169   76 ertgKRTYLLQAESEEERKDWIKAIQSAIR 105
PH_GRP1-like cd01252
General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 ...
 1949-2053 1.09e-09

General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 and the related proteins ARNO (ARF nucleotide-binding site opener)/cytohesin-2 and cytohesin-1 are ARF exchange factors that contain a pleckstrin homology (PH) domain thought to target these proteins to cell membranes through binding polyphosphoinositides. The PH domains of all three proteins exhibit relatively high affinity for PtdIns(3,4,5)P3. Within the Grp1 family, diglycine (2G) and triglycine (3G) splice variants, differing only in the number of glycine residues in the PH domain, strongly influence the affinity and specificity for phosphoinositides. The 2G variants selectively bind PtdIns(3,4,5)P3 with high affinity,the 3G variants bind PtdIns(3,4,5)P3 with about 30-fold lower affinity and require the polybasic region for plasma membrane targeting. These ARF-GEFs share a common, tripartite structure consisting of an N-terminal coiled-coil domain, a central domain with homology to the yeast protein Sec7, a PH domain, and a C-terminal polybasic region. The Sec7 domain is autoinhibited by conserved elements proximal to the PH domain. GRP1 binds to the DNA binding domain of certain nuclear receptors (TRalpha, TRbeta, AR, ER, but not RXR), and can repress thyroid hormone receptor (TR)-mediated transactivation by decreasing TR-complex formation on thyroid hormone response elements. ARNO promotes sequential activation of Arf6, Cdc42 and Rac1 and insulin secretion. Cytohesin acts as a PI 3-kinase effector mediating biological responses including cell spreading and adhesion, chemotaxis, protein trafficking, and cytoskeletal rearrangements, only some of which appear to depend on their ability to activate ARFs. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269954  Cd Length: 119  Bit Score: 58.09  E-value: 1.09e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1949 NRSYEGTLYKKGAFMKPWKARWFVLdkTKHQLRYYDHRVDTECKGVIDLAEV--------------EAVAPGTP-TMGAP 2013
Cdd:cd01252      2 NPDREGWLLKLGGRVKSWKRRWFIL--TDNCLYYFEYTTDKEPRGIIPLENLsvrevedkkkpfcfELYSPSNGqVIKAC 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1622837365 2014 KT-VDEKAffdVKTTRRVYNFCAQDVPSAQQWVDRIQSCLS 2053
Cdd:cd01252     80 KTdSDGKV---VEGNHTVYRISAASEEERDEWIKSIKASIS 117
PH-GRAM cd10570
Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins ...
 1084-1173 2.81e-09

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: 55.85  E-value: 2.81e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1084 LLPAEGAVFLTTYRVIFTGMPTDplvgeQVVVRSFPVAALTKEKRISVQtpvdQLLQDGLQLRSCTFQLLKMAFDEEvgS 1163
Cdd:cd10570     16 KLPLEGTLYLSTYRLIFSSKADG-----DETKLVIPLVDITDVEKIAGA----SFLPSGLIITCKDFRTIKFSFDSE--D 84

                           90
                   ....*....|
gi 1622837365 1164 DSAELFRKQL 1173
Cdd:cd10570     85 EAVKVIARVL 94
PH_Gab2_2 cd13384
Grb2-associated binding protein family pleckstrin homology (PH) domain; The Gab subfamily ...
 1952-2048 2.95e-09

Grb2-associated binding protein family pleckstrin homology (PH) domain; The Gab subfamily includes several Gab proteins, Drosophila DOS and C. elegans SOC-1. They are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. Members here include insect, nematodes, and crustacean Gab2s. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241535  Cd Length: 115  Bit Score: 56.68  E-value: 2.95e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1952 YEGTLYK----KGAFMKPWKARWFVLDKT----KHQLRYYDHRVDTECKGVIDLAEVEAVAPGTpTMGAPKTVDEKAFFD 2023
Cdd:cd13384      5 YEGWLTKsppeKRIWRAKWRRRYFVLRQSeipgQYFLEYYTDRTCRKLKGSIDLDQCEQVDAGL-TFETKNKLKDQHIFD 83

                           90       100
                   ....*....|....*....|....*
gi 1622837365 2024 VKTTRRVYNFCAQDVPSAQQWVDRI 2048
Cdd:cd13384     84 IRTPKRTYYLVADTEDEMNKWVNCI 108
PH_ORP10_ORP11 cd13291
Human Oxysterol binding protein (OSBP) related proteins 10 and 11 (ORP10 and ORP11) Pleckstrin ...
 1952-2051 3.24e-09

Human Oxysterol binding protein (OSBP) related proteins 10 and 11 (ORP10 and ORP11) Pleckstrin homology (PH) domain; Human ORP10 is involvedt in intracellular transport or organelle positioning and is proposed to function as a regulator of cellular lipid metabolism. Human ORP11 localizes at the Golgi-late endosome interface and is thought to form a dimer with ORP9 functioning as an intracellular lipid sensor or transporter. Both ORP10 and ORP11 contain a N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270106  Cd Length: 107  Bit Score: 56.15  E-value: 3.24e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1952 YEGTLYKKGAFMKPWKARWFVLDKTKHQLRYY--DHRVDTECKGVIDLAevEAVApgtptmgAPKTVDEKAFFDVKTTRR 2029
Cdd:cd13291      1 LEGQLLKYTNVVKGWQNRWFVLDPDTGILEYFlsEESKNQKPRGSLSLA--GAVI-------SPSDEDSHTFTVNAANGE 71

                           90       100
                   ....*....|....*....|..
gi 1622837365 2030 VYNFCAQDVPSAQQWVDRIQSC 2051
Cdd:cd13291     72 MYKLRAADAKERQEWVNRLRAV 93
PH2_MyoX cd13296
Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular ...
 1954-2053 5.85e-09

Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular motor that has crucial functions in the transport and/or tethering of integrins in the actin-based extensions known as filopodia, microtubule binding, and in netrin-mediated axon guidance. It functions as a dimer. MyoX walks on bundles of actin, rather than single filaments, unlike the other unconventional myosins. MyoX is present in organisms ranging from humans to choanoflagellates, but not in Drosophila and Caenorhabditis elegans.MyoX consists of a N-terminal motor/head region, a neck made of 3 IQ motifs, and a tail consisting of a coiled-coil domain, a PEST region, 3 PH domains, a myosin tail homology 4 (MyTH4), and a FERM domain at its very C-terminus. The first PH domain in the MyoX tail is a split-PH domain, interupted by the second PH domain such that PH 1a and PH 1b flanks PH 2. The third PH domain (PH 3) follows the PH 1b domain. This cd contains the second PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270108  Cd Length: 103  Bit Score: 55.55  E-value: 5.85e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1954 GTLYKKGAFM-----KPWKARWFVLDKTKhqLRYYDHRVDTE-CKGVIDLAEVEAVAPGTPTMGApktvdekafFDVKTT 2027
Cdd:cd13296      3 GWLTKKGGGSstlsrRNWKSRWFVLRDTV--LKYYENDQEGEkLLGTIDIRSAKEIVDNDPKENR---------LSITTE 71

                           90       100
                   ....*....|....*....|....*.
gi 1622837365 2028 RRVYNFCAQDVPSAQQWVDRIQSCLS 2053
Cdd:cd13296     72 ERTYHLVAESPEDASQWVNVLTRVIS 97
PH_Gab-like cd13324
Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are ...
 1952-2048 1.75e-08

Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. There are 3 families: Gab1, Gab2, and Gab3. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270133  Cd Length: 112  Bit Score: 54.34  E-value: 1.75e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1952 YEGTLYK----KGAFMKPWKARWFVLDKTK-----HQLRYYDHRVDTECKGVIDLAEVEAVAPGTPTmgAPKTVDEKAFF 2022
Cdd:cd13324      3 YEGWLTKsppeKKIWRAAWRRRWFVLRSGRlsggqDVLEYYTDDHCKKLKGIIDLDQCEQVDAGLTF--EKKKFKNQFIF 80

                           90       100
                   ....*....|....*....|....*.
gi 1622837365 2023 DVKTTRRVYNFCAQDVPSAQQWVDRI 2048
Cdd:cd13324     81 DIRTPKRTYYLVAETEEEMNKWVRCI 106
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
 1953-2053 2.90e-08

Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 (PLEKHH1) PH domain, repeat 1; PLEKHH1 and PLEKHH2 (also called PLEKHH1L) are thought to function in phospholipid binding and signal transduction. There are 3 Human PLEKHH genes: PLEKHH1, PLEKHH2, and PLEKHH3. There are many isoforms, the longest of which contain a FERM domain, a MyTH4 domain, two PH domains, a peroximal domain, a vacuolar domain, and a coiled coil stretch. The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C/N, alpha-, and C-lobe/A-lobe, B-lobe, C-lobe/F1, F2, F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241436  Cd Length: 96  Bit Score: 53.07  E-value: 2.90e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1953 EGTLYKKGAFMKPWKARWFVLDKTkhQLRYYDHRVDTECK--GVIDLAEVEAVAPGtptmgapktvDEKAFFDVKTTRRV 2030
Cdd:cd13282      2 AGYLTKLGGKVKTWKRRWFVLKNG--ELFYYKSPNDVIRKpqGQIALDGSCEIARA----------EGAQTFEIVTEKRT 69

                           90       100
                   ....*....|....*....|...
gi 1622837365 2031 YNFCAQDVPSAQQWVDRIQSCLS 2053
Cdd:cd13282     70 YYLTADSENDLDEWIRVIQNVLR 92
PH_RASA1 cd13260
RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 ...
 1954-2051 1.28e-07

RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 (also called RasGap1 or p120) is a member of the RasGAP family of GTPase-activating proteins. RASA1 contains N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Splice variants lack the N-terminal domains. It is a cytosolic vertebrate protein that acts as a suppressor of RAS via its C-terminal GAP domain function, enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. Additionally, it is involved in mitogenic signal transmission towards downstream interacting partners through its N-terminal SH2-SH3-SH2 domains. RASA1 interacts with a number of proteins including: G3BP1, SOCS3, ANXA6, Huntingtin, KHDRBS1, Src, EPHB3, EPH receptor B2, Insulin-like growth factor 1 receptor, PTK2B, DOK1, PDGFRB, HCK, Caveolin 2, DNAJA3, HRAS, GNB2L1 and NCK1. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270080  Cd Length: 103  Bit Score: 51.58  E-value: 1.28e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1954 GTLYKKGAFMKPWKARWFVLDKTKHQLRYYDHRVDTECKGVIDLAE--VEAVAPGtpTMGAPK--TVDEKAFFDVkttrR 2029
Cdd:cd13260      7 GYLLKKGGKNKKWKNLYFVLEGKEQHLYFFDNEKRTKPKGLIDLSYcsLYPVHDS--LFGRPNcfQIVVRALNES----T 80

                           90       100
                   ....*....|....*....|..
gi 1622837365 2030 VYNFCAQDVPSAQQWVDRIQSC 2051
Cdd:cd13260     81 ITYLCADTAELAQEWMRALRAF 102
PH2_ADAP cd01251
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called ...
 1953-2053 7.52e-07

ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity. This cd contains the second PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241282  Cd Length: 105  Bit Score: 49.51  E-value: 7.52e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1953 EGTLYKKGAFMK-PWKARWFVLDKTKhqLRYYDHRVDTECKGVIDLAEVE---AVAPGTPTmGAPKTVDEKafFDVKTTR 2028
Cdd:cd01251      5 EGYLEKTGPKQTdGFRKRWFTLDDRR--LMYFKDPLDAFPKGEIFIGSKEegySVREGLPP-GIKGHWGFG--FTLVTPD 79

                           90       100
                   ....*....|....*....|....*
gi 1622837365 2029 RVYNFCAQDVPSAQQWVDRIQSCLS 2053
Cdd:cd01251     80 RTFLLSAETEEERREWITAIQKVLE 104
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
 1953-2052 1.18e-06

Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all plant tissue and is proposed to be the plant homolog of human pleckstrin. Pleckstrin consists of two PH domains separated by a linker region, while AtPH has a single PH domain with a short N-terminal extension. AtPH1 binds PtdIns3P specifically and is thought to be an adaptor molecule since it has no obvious catalytic functions. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270095  Cd Length: 106  Bit Score: 48.85  E-value: 1.18e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1953 EGTLYKKGAFMKPWKARWFVLDKTK-HQLRYYDHRVDTECKGVIDLAEVEAVApgtptmGAPKTVDEKAFFDVKTTRRVY 2031
Cdd:cd13276      2 AGWLEKQGEFIKTWRRRWFVLKQGKlFWFKEPDVTPYSKPRGVIDLSKCLTVK------SAEDATNKENAFELSTPEETF 75

                           90       100
                   ....*....|....*....|.
gi 1622837365 2032 NFCAQDVPSAQQWVDRIQSCL 2052
Cdd:cd13276     76 YFIADNEKEKEEWIGAIGRAI 96
PH1_Pleckstrin_2 cd13301
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in ...
 1953-1997 1.41e-06

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. This cd contains the first PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270113  Cd Length: 108  Bit Score: 48.91  E-value: 1.41e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*
gi 1622837365 1953 EGTLYKKGAFMKPWKARWFVLdkTKHQLRYYDHRVDTECKGVIDL 1997
Cdd:cd13301      6 EGYLVKKGHVVNNWKARWFVL--KEDGLEYYKKKTDSSPKGMIPL 48
PH_Btk cd01238
Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of ...
 1953-2007 1.49e-06

Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of cytoplasmic protein tyrosine kinases that includes BMX, IL2-inducible T-cell kinase (Itk) and Tec. Btk plays a role in the maturation of B cells. Tec proteins general have an N-terminal PH domain, followed by a Tek homology (TH) domain, a SH3 domain, a SH2 domain and a kinase domain. The Btk PH domain binds phosphatidylinositol 3,4,5-trisphosphate and responds to signalling via phosphatidylinositol 3-kinase. The PH domain is also involved in membrane anchoring which is confirmed by the discovery of a mutation of a critical arginine residue in the BTK PH domain. This results in severe human immunodeficiency known as X-linked agammaglobulinemia (XLA) in humans and a related disorder is mice.PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269944 [Multi-domain]  Cd Length: 140  Bit Score: 49.53  E-value: 1.49e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1622837365 1953 EGTLYKKG---AFMKP--WKARWFVLdkTKHQLRYYDHRVDT--ECKGVIDLAE---VEAVAPGT 2007
Cdd:cd01238      2 EGLLVKRSqgkKRFGPvnYKERWFVL--TKSSLSYYEGDGEKrgKEKGSIDLSKvrcVEEVKDEA 64
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
 1946-2048 2.79e-06

Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP2 contains two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. The members here are most sequence similar to TAPP2 proteins, but may not be actual TAPP2 proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270075  Cd Length: 110  Bit Score: 47.79  E-value: 2.79e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1946 ESENRSYEGTLYKKGAFMKPWKARWFVLDKTKhqLRYYDHRVDTECKGVIDLAEVEAVAPgtptmgapktVDEKAF---F 2022
Cdd:cd13255      2 ISEAVLKAGYLEKKGERRKTWKKRWFVLRPTK--LAYYKNDKEYRLLRLIDLTDIHTCTE----------VQLKKHdntF 69

                           90       100
                   ....*....|....*....|....*.
gi 1622837365 2023 DVKTTRRVYNFCAQDVPSAQQWVDRI 2048
Cdd:cd13255     70 GIVTPARTFYVQADSKAEMESWISAI 95
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
 1953-2049 2.82e-06

Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, repeat 1; ATG26 (also called UGT51/UDP-glycosyltransferase 51), a member of the glycosyltransferase 28 family, resulting in the biosynthesis of sterol glucoside. ATG26 in decane metabolism and autophagy. There are 32 known autophagy-related (ATG) proteins, 17 are components of the core autophagic machinery essential for all autophagy-related pathways and 15 are the additional components required only for certain pathways or species. The core autophagic machinery includes 1) the ATG9 cycling system (ATG1, ATG2, ATG9, ATG13, ATG18, and ATG27), 2) the phosphatidylinositol 3-kinase complex (ATG6/VPS30, ATG14, VPS15, and ATG34), and 3) the ubiquitin-like protein system (ATG3, ATG4, ATG5, ATG7, ATG8, ATG10, ATG12, and ATG16). Less is known about how the core machinery is adapted or modulated with additional components to accommodate the nonselective sequestration of bulk cytosol (autophagosome formation) or selective sequestration of specific cargos (Cvt vesicle, pexophagosome, or bacteria-containing autophagosome formation). The pexophagosome-specific additions include the ATG30-ATG11-ATG17 receptor-adaptors complex, the coiled-coil protein ATG25, and the sterol glucosyltransferase ATG26. ATG26 is necessary for the degradation of medium peroxisomes. It contains 2 GRAM domains and a single PH domain. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains also have diverse functions. They are often involved in targeting proteins to the plasma membrane, but few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 275402  Cd Length: 116  Bit Score: 48.00  E-value: 2.82e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1953 EGTLYKKGAFMKPWKARWFVLdktKHQ-LRYYdhRVDTEC---KGVIDLAEVEAVAPGTPTMGAPKTvdekafFDVKTTR 2028
Cdd:cd13215     24 SGYLSKRSKRTLRYTRYWFVL---KGDtLSWY--NSSTDLyfpAGTIDLRYATSIELSKSNGEATTS------FKIVTNS 92

                           90       100
                   ....*....|....*....|.
gi 1622837365 2029 RVYNFCAQDVPSAQQWVDRIQ 2049
Cdd:cd13215     93 RTYKFKADSETSADEWVKALK 113
dDENN pfam03455
dDENN domain; This region is always found associated with pfam02141. It is predicted to form a ...
 561-607 5.16e-06

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.


Pssm-ID: 460925  Cd Length: 48  Bit Score: 45.26  E-value: 5.16e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1622837365  561 FHKAAFLGQRGLVEDDFLMKVLEGMAFAGFVSERGVPYRPT-DLFDEL 607
Cdd:pfam03455    1 FDKEAFLKSLPSDSRPFLSQFLETQMFNEFIEERLESSDPSiDLFDEE 48
GRAM smart00568
domain in glucosyltransferases, myotubularins and other putative membrane-associated proteins;
1052-1130 7.03e-06

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


Pssm-ID: 214725 [Multi-domain]  Cd Length: 60  Bit Score: 45.28  E-value: 7.03e-06
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1622837365  1052 LPGEECVLDGLRVYLLPDGreegaggsaggpallPAEGAVFLTTYRVIFTGMPTDPLvgeqvVVRSFPVAALTKEKRIS 1130
Cdd:smart00568    2 LPEEEKLIADYSCYLSRTG---------------PVQGRLYISNYRLCFRSNLPGKL-----TKVVIPLADITRIEKST 60
PH_GPBP cd13283
Goodpasture antigen binding protein Pleckstrin homology (PH) domain; The GPBP (also called ...
 1953-2050 6.59e-05

Goodpasture antigen binding protein Pleckstrin homology (PH) domain; The GPBP (also called Collagen type IV alpha-3-binding protein/hCERT; START domain-containing protein 11/StARD11; StAR-related lipid transfer protein 11) is a kinase that phosphorylates an N-terminal region of the alpha 3 chain of type IV collagen, which is commonly known as the goodpasture antigen. Its splice variant the ceramide transporter (CERT) mediates the cytosolic transport of ceramide. There have been additional splice variants identified, but all of them function as ceramide transport proteins. GPBP and CERT both contain an N-terminal PH domain, followed by a serine rich domain, and a C-terminal START domain. However, GPBP has an additional serine rich domain just upstream of its START domain. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270100 [Multi-domain]  Cd Length: 100  Bit Score: 43.81  E-value: 6.59e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1953 EGTLYKKGAFMKPWKARWFVL-DKTkhqLRYYDHRVDTE--CKGVIDLAEVEAvapgtptmgAPKTVDEKAFfDVKTTRR 2029
Cdd:cd13283      2 RGVLSKWTNYIHGWQDRYFVLkDGT---LSYYKSESEKEygCRGSISLSKAVI---------KPHEFDECRF-DVSVNDS 68

                           90       100
                   ....*....|....*....|.
gi 1622837365 2030 VYNFCAQDVPSAQQWVDRIQS 2050
Cdd:cd13283     69 VWYLRAESPEERQRWIDALES 89
PH2_TAPP1_2 cd13271
Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal ...
 1958-2003 6.84e-05

Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal repeat; The binding of TAPP1 (also called PLEKHA1/pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 1) and TAPP2 (also called PLEKHA2) adaptors to PtdIns(3,4)P(2), but not PI(3,4, 5)P3, function as negative regulators of insulin and PI3K signalling pathways (i.e. TAPP/utrophin/syntrophin complex). TAPP1 and TAPP2 contain two sequential PH domains in which the C-terminal PH domain specifically binds PtdIns(3,4)P2 with high affinity. The N-terminal PH domain does not interact with any phosphoinositide tested. They also contain a C-terminal PDZ-binding motif that interacts with several PDZ-binding proteins, including PTPN13 (known previously as PTPL1 or FAP-1) as well as the scaffolding proteins MUPP1 (multiple PDZ-domain-containing protein 1), syntrophin and utrophin. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270090  Cd Length: 114  Bit Score: 44.27  E-value: 6.84e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1622837365 1958 KKGAFMKPWKARWFVLDktKHQLRYYDHRVDTECKGVIDLAEVEAV 2003
Cdd:cd13271     16 KQGAVRKNWKRRFFILD--DNTISYYKSETDKEPLRTIPLREVLKV 59
PH1_ADAP cd13252
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 1; ADAP (also called ...
 1951-2003 8.38e-05

ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 1; ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity. This cd contains the first PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270072  Cd Length: 109  Bit Score: 43.79  E-value: 8.38e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1622837365 1951 SYEGTLYKKGAFMKPWKARWFVLDKTKHQLRYYDHRVDTECKGVIDLAEVEAV 2003
Cdd:cd13252      2 SKEGFLWKRGKDNNQFKQRKFVLSEREGTLKYFVKEDAKEPKAVISIEELNAT 54
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
 1954-2046 1.29e-04

Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; PEPP1 (also called PLEKHA4/PH domain-containing family A member 4 and RHOXF1/Rhox homeobox family member 1), and related homologs PEPP2 (also called PLEKHA5/PH domain-containing family A member 5) and PEPP3 (also called PLEKHA6/PH domain-containing family A member 6), have PH domains that interact specifically with PtdIns(3,4)P3. Other proteins that bind PtdIns(3,4)P3 specifically are: TAPP1 (tandem PH-domain-containing protein-1) and TAPP2], PtdIns3P AtPH1, and Ptd- Ins(3,5)P2 (centaurin-beta2). All of these proteins contain at least 5 of the 6 conserved amino acids that make up the putative phosphatidylinositol 3,4,5- trisphosphate-binding motif (PPBM) located at their N-terminus. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270068  Cd Length: 104  Bit Score: 43.03  E-value: 1.29e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1954 GTLYKK-GAFMKPWKARWFVLdkTKHQLRYYDHRVDTECKGVIDLaeveavaPG---TPTMGAPKTVDEKAFFDVKTTRR 2029
Cdd:cd13248     11 GWLHKQgGSGLKNWRKRWFVL--KDNCLYYYKDPEEEKALGSILL-------PSytiSPAPPSDEISRKFAFKAEHANMR 81

                           90
                   ....*....|....*..
gi 1622837365 2030 VYNFCAQDVPSAQQWVD 2046
Cdd:cd13248     82 TYYFAADTAEEMEQWMN 98
PH_ORP9 cd13290
Human Oxysterol binding protein related protein 9 Pleckstrin homology (PH) domain; Human ORP9 ...
 1953-2049 1.84e-04

Human Oxysterol binding protein related protein 9 Pleckstrin homology (PH) domain; Human ORP9 is proposed to function in regulation of Akt phosphorylation. ORP9 has 2 forms, a long (ORP9L) and a short (ORP9S). ORP9L contains an N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. ORP1S is truncated and contains a FFAT motif and an OSBP-related domain. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241444  Cd Length: 102  Bit Score: 42.43  E-value: 1.84e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1953 EGTLYKKGAFMKPWKARWFVLDKTKHQLRYYDHRvDTECKGV----IDLAeveavapgtptmGAPKTVD--EKAFFDVKT 2026
Cdd:cd13290      2 EGPLSKWTNVMKGWQYRWFVLDDNAGLLSYYTSK-EKMMRGSrrgcVRLK------------GAVVGIDdeDDSTFTITV 68

                           90       100
                   ....*....|....*....|...
gi 1622837365 2027 TRRVYNFCAQDVPSAQQWVDRIQ 2049
Cdd:cd13290     69 DQKTFHFQARDAEERERWIRALE 91
PH_FAPP1_FAPP2 cd01247
Four phosphate adaptor protein 1 and 2 Pleckstrin homology (PH) domain; Human FAPP1 (also ...
 1953-2004 2.03e-04

Four phosphate adaptor protein 1 and 2 Pleckstrin homology (PH) domain; Human FAPP1 (also called PLEKHA3/Pleckstrin homology domain-containing, family A member 3) regulates secretory transport from the trans-Golgi network to the plasma membrane. It is recruited through binding of PH domain to phosphatidylinositol 4-phosphate (PtdIns(4)P) and a small GTPase ADP-ribosylation factor 1 (ARF1). These two binding sites have little overlap the FAPP1 PH domain to associate with both ligands simultaneously and independently. FAPP1 has a N-terminal PH domain followed by a short proline-rich region. FAPP1 is a member of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), and Goodpasture antigen binding protein (GPBP). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. FAPP2 (also called PLEKHA8/Pleckstrin homology domain-containing, family A member 8), a member of the Glycolipid lipid transfer protein(GLTP) family has an N-terminal PH domain that targets the TGN and C-terminal GLTP domain. FAPP2 functions to traffic glucosylceramide (GlcCer) which is made in the Golgi. It's interaction with vesicle-associated membrane protein-associated protein (VAP) could be a means of regulation. Some FAPP2s share the FFAT-like motifs found in GLTP. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269951  Cd Length: 100  Bit Score: 42.39  E-value: 2.03e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1622837365 1953 EGTLYKKGAFMKPWKARWFVLDKTkhQLRYYDHR--VDTECKGVIDLAEVEAVA 2004
Cdd:cd01247      2 EGVLWKWTNYLSGWQPRWFVLDDG--VLSYYKSQeeVNQGCKGSVKMSVCEIIV 53
SPA pfam08616
Stabilization of polarity axis; Swiss:Q99222 has been shown to interact with the outer plaque ...
 384-474 6.62e-04

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.


Pssm-ID: 400783  Cd Length: 113  Bit Score: 41.12  E-value: 6.62e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365  384 NVLSLFCAALTEHKVLFLsrSYQRLADA-CRGLLALL------FPLRY----SFTYVPIlpAQLLEVLSTPtPFIIGV-N 451
Cdd:pfam08616   14 PIILLINALLTSKRIIFL--SYQRSAGEvSEFVLALCnlisggFVLRGftnnSFPYVDL--SKLDALRKVP-GYIAGVtN 88

                           90       100
                   ....*....|....*....|...
gi 1622837365  452 AAFqAETQELLDVIVaDLDGGTV 474
Cdd:pfam08616   89 PIF-ENQDQWWDVLC-DLDSGSV 109
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
 1953-2045 1.19e-03

Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 mammalian members: Ses1 and Ses2, which are also callled 7 kDa inositol polyphosphate phosphatase-interacting protein 1 and 2. They play a role in endocytic trafficking and are required for receptor recycling from endosomes, both to the trans-Golgi network and the plasma membrane. Members of this family form homodimers and heterodimers. Sesquipedalian interacts with inositol polyphosphate 5-phosphatase OCRL-1 (INPP5F) also known as Lowe oculocerebrorenal syndrome protein, a phosphatase enzyme that is involved in actin polymerization and is found in the trans-Golgi network and INPP5B. Sesquipedalian contains a single PH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270105 [Multi-domain]  Cd Length: 120  Bit Score: 40.68  E-value: 1.19e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1953 EGTLYKKGAFMKPWKARWFVLdkTKHQLRYYDHRVDTECKGVIDLAE--VEAVApgtptmgapkTVDEKAF---FDVKTT 2027
Cdd:cd13288     11 EGYLWKKGERNTSYQKRWFVL--KGNLLFYFEKKGDREPLGVIVLEGctVELAE----------DAEPYAFairFDGPGA 78

                           90
                   ....*....|....*...
gi 1622837365 2028 rRVYNFCAQDVPSAQQWV 2045
Cdd:cd13288     79 -RSYVLAAENQEDMESWM 95
PH2_PH_fungal cd13299
Fungal proteins Pleckstrin homology (PH) domain, repeat 2; The functions of these fungal ...
 1952-2052 1.64e-03

Fungal proteins Pleckstrin homology (PH) domain, repeat 2; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the second PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270111  Cd Length: 102  Bit Score: 39.92  E-value: 1.64e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1952 YEGTLYK-KGAFMKPWKARWFVLdkTKHQLRYYDHRVDTECKGVIDLAEVEAVAPGTPTmgapkTVDEKAFFDVKTTRRV 2030
Cdd:cd13299      8 EQGYLQVlKKKGVNQWKKYWLVL--RNRSLSFYKDQSEYSPVKIIPIDDIIDVVELDPL-----SKSKKWCLQIITPEKR 80

                           90       100
                   ....*....|....*....|..
gi 1622837365 2031 YNFCAQDVPSAQQWVDRIQSCL 2052
Cdd:cd13299     81 IRFCADDEESLIKWLGALKSLL 102
Niban-like cd23949
Niban-like protein; Niban-like proteins contain an N-terminal Pleckstrin-Homology (PH) domain ...
 1946-2052 1.78e-03

Niban-like protein; Niban-like proteins contain an N-terminal Pleckstrin-Homology (PH) domain that may be involved in binding to specific ligands. Phosphatidylinositol (3)-phosphate (PI3P) was recognized as the innate ligand of the PH domain of MINERVA (melanoma invasion by ERK, also known as FAM129B) PH. Niban family proteins have been found to regulate phosphorylation of a number of proteins involved in the regularion of translation, such as EIF2A, EIF4EBP1 and RPS6KB1. They may also be involved in the endoplasmic reticulum stress response (FAM129A, Niban-like protein 1), suggested to play a role in apoptosis suppression in cancer cells, while Niban-like protein 2 (FAM129C) is a B-cell membrane protein that is overexpressed in chronic lymphocytic leukemia.


Pssm-ID: 469558 [Multi-domain]  Cd Length: 550  Bit Score: 43.44  E-value: 1.78e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1946 ESENRSYEGTLYKKGAFMKPWKARWFVLdKTKHQLRYYDHRVDTE----CKGVIDLAEVEAVAPGT----------PTMG 2011
Cdd:cd23949     58 EDRKVIFSGKLSKYGEDSKKWKERFCVV-RGDYNLEYYESKEAYErgkkPKGSINLAGYKVLTSPEeylelvdrkfPDLA 136

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1622837365 2012 APKTVDEKAFFDVKTT---------RRVYNFCAQDVPSAQQWVDRIQSCL 2052
Cdd:cd23949    137 GKSEKASVPFPERPPPftlelyhpyRRHYYFCFETEKEQEEWVAVLQDCI 186
PH_Osh1p_Osh2p_yeast cd13292
Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p ...
 1950-1998 1.82e-03

Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p is proposed to function in postsynthetic sterol regulation, piecemeal microautophagy of the nucleus, and cell polarity establishment. Yeast Osh2p is proposed to function in sterol metabolism and cell polarity establishment. Both Osh1p and Osh2p contain 3 N-terminal ankyrin repeats, a PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. OSBP andOsh1p PH domains specifically localize to the Golgi apparatus in a PtdIns4P-dependent manner. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. In general OSBPs and ORPs have been found to be involved in the transport and metabolism of cholesterol and related lipids in eukaryotes. They all contain a C-terminal oxysterol binding domain, and most contain an N-terminal PH domain. OSBP PH domains bind to membrane phosphoinositides and thus likely play an important role in intracellular targeting. They are members of the oxysterol binding protein (OSBP) family which includes OSBP, OSBP-related proteins (ORP), Goodpasture antigen binding protein (GPBP), and Four phosphate adaptor protein 1 (FAPP1). They have a wide range of purported functions including sterol transport, cell cycle control, pollen development and vessicle transport from Golgi recognize both PI lipids and ARF proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 241446  Cd Length: 103  Bit Score: 39.60  E-value: 1.82e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1622837365 1950 RSYEGTLYKKGAFMKPWKARWFVLDKTkhQLRYYDHRVD--TECKGVIDLA 1998
Cdd:cd13292      2 PTMKGYLKKWTNYAKGYKTRWFVLEDG--VLSYYRHQDDegSACRGSINMK 50
PH_Boi cd13316
Boi family Pleckstrin homology domain; Yeast Boi proteins Boi1 and Boi2 are functionally ...
 1952-1997 2.15e-03

Boi family Pleckstrin homology domain; Yeast Boi proteins Boi1 and Boi2 are functionally redundant and important for cell growth with Boi mutants displaying defects in bud formation and in the maintenance of cell polarity.They appear to be linked to Rho-type GTPase, Cdc42 and Rho3. Boi1 and Boi2 display two-hybrid interactions with the GTP-bound ("active") form of Cdc42, while Rho3 can suppress of the lethality caused by deletion of Boi1 and Boi2. These findings suggest that Boi1 and Boi2 are targets of Cdc42 that promote cell growth in a manner that is regulated by Rho3. Boi proteins contain a N-terminal SH3 domain, followed by a SAM (sterile alpha motif) domain, a proline-rich region, which mediates binding to the second SH3 domain of Bem1, and C-terminal PH domain. The PH domain is essential for its function in cell growth and is important for localization to the bud, while the SH3 domain is needed for localization to the neck. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270126  Cd Length: 97  Bit Score: 39.28  E-value: 2.15e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*.
gi 1622837365 1952 YEGTLYKKGAFMKPWKARWFVLDKTkhQLRYYDHRVDTECKGVIDL 1997
Cdd:cd13316      2 HSGWMKKRGERYGTWKTRYFVLKGT--RLYYLKSENDDKEKGLIDL 45
PH_evt cd13265
Evectin Pleckstrin homology (PH) domain; There are 2 members of the evectin family (also ...
 1954-2045 2.52e-03

Evectin Pleckstrin homology (PH) domain; There are 2 members of the evectin family (also called pleckstrin homology domain containing, family B): evt-1 (also called PLEKHB1) and evt-2 (also called PLEKHB2). evt-1 is specific to the nervous system, where it is expressed in photoreceptors and myelinating glia. evt-2 is widely expressed in both neural and nonneural tissues. Evectins possess a single N-terminal PH domain and a C-terminal hydrophobic region. evt-1 is thought to function as a mediator of post-Golgi trafficking in cells that produce large membrane-rich organelles. It is a candidate gene for the inherited human retinopathy autosomal dominant familial exudative vitreoretinopathy and a susceptibility gene for multiple sclerosis. evt-2 is essential for retrograde endosomal membrane transport from the plasma membrane (PM) to the Golgi. Two membrane trafficking pathways pass through recycling endosomes: a recycling pathway and a retrograde pathway that links the PM to the Golgi/ER. Its PH domain that is unique in that it specifically recognizes phosphatidylserine (PS), but not polyphosphoinositides. PS is an anionic phospholipid class in eukaryotic biomembranes, is highly enriched in the PM, and plays key roles in various physiological processes such as the coagulation cascade, recruitment and activation of signaling molecules, and clearance of apoptotic cells. PH domains are only found in eukaryotes. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270085  Cd Length: 108  Bit Score: 39.59  E-value: 2.52e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1954 GTLYKKGAFMKPWKARWFVLdKTKHQLRYYDHRVDTECKGVIDL-AEVEAVAPGT--PTMGAPKTVDEKAFFDVKT-TRR 2029
Cdd:cd13265      7 GWLLRQSTILKRWKKNWFVL-YGDGNLVYYEDETRREVEGRINMpRECRNIRVGLecRDVQPPEGRSRDCLLQIVLrDGS 85

                           90
                   ....*....|....*.
gi 1622837365 2030 VYNFCAQDVPSAQQWV 2045
Cdd:cd13265     86 TLFLCAESADDALAWK 101
PH_Gab3 cd13385
Grb2-associated binding protein 3 pleckstrin homology (PH) domain; The Gab subfamily includes ...
 1966-2051 3.68e-03

Grb2-associated binding protein 3 pleckstrin homology (PH) domain; The Gab subfamily includes several Gab proteins, Drosophila DOS and C. elegans SOC-1. They are scaffolding adaptor proteins, which possess N-terminal PH domains and a C-terminus with proline-rich regions and multiple phosphorylation sites. Following activation of growth factor receptors, Gab proteins are tyrosine phosphorylated and activate PI3K, which generates 3-phosphoinositide lipids. By binding to these lipids via the PH domain, Gab proteins remain in proximity to the receptor, leading to further signaling. While not all Gab proteins depend on the PH domain for recruitment, it is required for Gab activity. The members in this cd include the Gab1, Gab2, and Gab3 proteins. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270184  Cd Length: 125  Bit Score: 39.57  E-value: 3.68e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1966 WKARWFVLDKTKHQ-----LRYYDHRVDTECKGVIDLAEVEAVAPGTPTMgAPKTVDEKAFFDVKTTRRVYNFCAQDVPS 2040
Cdd:cd13385     26 WRKRWFVLRRGRMSgnpdvLEYYRNNHSKKPIRVIDLSECEVLKHSGPNF-IRKEFQNNFVFIVKTTYRTFYLVAKTEEE 104

                           90
                   ....*....|..
gi 1622837365 2041 AQQWVDRI-QSC 2051
Cdd:cd13385    105 MQVWVHNIsQIC 116
PH_M-RIP cd13275
Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed ...
 1954-2005 4.13e-03

Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed to play a role in myosin phosphatase regulation by RhoA. M-RIP contains 2 PH domains followed by a Rho binding domain (Rho-BD), and a C-terminal myosin binding subunit (MBS) binding domain (MBS-BD). The amino terminus of M-RIP with its adjacent PH domains and polyproline motifs mediates binding to both actin and Galpha. M-RIP brings RhoA and MBS into close proximity where M-RIP can target RhoA to the myosin phosphatase complex to regulate the myosin phosphorylation state. M-RIP does this via its C-terminal coiled-coil domain which interacts with the MBS leucine zipper domain of myosin phosphatase, while its Rho-BD, directly binds RhoA in a nucleotide-independent manner. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270094  Cd Length: 104  Bit Score: 38.85  E-value: 4.13e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1622837365 1954 GTLYKKGAFMKPWKARWFVLdkTKHQLRYY-DHRVD--TECKGVIDLAEVEAVAP 2005
Cdd:cd13275      3 GWLMKQGSRQGEWSKHWFVL--RGAALKYYrDPSAEeaGELDGVIDLSSCTEVTE 55
PHA03247 PHA03247
large tegument protein UL36; Provisional
 34-156 5.20e-03

large tegument protein UL36; Provisional


Pssm-ID: 223021 [Multi-domain]  Cd Length: 3151  Bit Score: 42.23  E-value: 5.20e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365   34 PHPSPPRmeqlSPRKDPsrnravkygPLWSQRARGRQLPLPETFPTVAEDRPEAFPA-----RPRRDRKRSLRGRGQRAT 108
Cdd:PHA03247  2614 PSPLPPD----THAPDP---------PPPSPSPAANEPDPHPPPTVPPPERPRDDPApgrvsRPRRARRLGRAAQASSPP 2680

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1622837365  109 RLFHARGVKDP----DELEHPQLPSDNTEDRPPPLLKALVPPTNQTEPGEAS 156
Cdd:PHA03247  2681 QRPRRRAARPTvgslTSLADPPPPPPTPEPAPHALVSATPLPPGPAAARQAS 2732
PH_GAP1-like cd01244
RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; ...
 1953-2046 6.97e-03

RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; RASAL1, GAP1(m), GAP1(IP4BP), and CAPRI are all members of the GAP1 family of GTPase-activating proteins. They contain N-terminal SH2-SH3-SH2 domains, followed by two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. With the notable exception of GAP1(m), they all possess an arginine finger-dependent GAP activity on the Ras-related protein Rap1. They act as a suppressor of RAS enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS, allowing control of cellular proliferation and differentiation. PH domains share little sequence conservation, but all have a common fold, which is electrostatically polarized. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269950  Cd Length: 107  Bit Score: 38.04  E-value: 6.97e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1622837365 1953 EGTLYK------KGAFMKPWKARWFVLdkTKHQLRYYDHRVDTECKgVIDLAEVEAVapgtptmgapKTVDEKAF----- 2021
Cdd:cd01244      2 EGYLIKraqgrkKKFGRKNFKKRYFRL--TNEALSYSKSKGKQPLC-SIPLEDILAV----------ERVEEESFkmknm 68

                           90       100
                   ....*....|....*....|....*
gi 1622837365 2022 FDVKTTRRVYNFCAQDVPSAQQWVD 2046
Cdd:cd01244     69 FQIVQPDRTLYLQAKNVVELNEWLS 93
 
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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