NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|568993627|ref|XP_006521601|]
View 

myotubularin-related protein 5 isoform X1 [Mus musculus]

Protein Classification

DENN domain-containing protein( domain architecture ID 13925258)

DENN domain-containing protein may be involved in Rab-mediated processes or regulation of mitogen-activated protein kinase (MAPK) signalling pathways

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

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 ...
 1158-1530 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: 573.84  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1158 FRISPVNRMYAICRSYPGLLIVPQSIQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLLRSGGLHGKGVVGLFKAQNTPSP 1237
Cdd:cd14588     1 FRISTVNRMYAVCRSYPGLLIVPQSIQDNTIQRISRCYRQNRFPVVCWRNSRTKAVLLRSGGLHGKGVVGLFKSQNAPAA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1238 GQAQADSSSLEQEKYLQAVVSSMPRYADSSGRNTLSSFssahmgghvpsprarvttlsnplaasasrwtasrgkwssvra 1317
Cdd:cd14588    81 GQSQTDSTSLEQEKYLQAVINSMPRYADASGRNTLSGF------------------------------------------ 118

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1318 sgrssglgsdvgsrlagrdllstphtngappdsgflrpqRAALYIIGDKAQLKGVRPDPLQQWELVPIEVFEARQVKASF 1397
Cdd:cd14588   119 ---------------------------------------RAALYIIGDKSQLKGVKQDPLQQWEVVPIEVFDVRQVKASF 159

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1398 KKLLKACVPGCPATePSPASFLRSLEDSEWLIQIHKLLQISVLVVELLDSGSSVLVSLEDGWDITTQVVSLVQLLSDPFY 1477
Cdd:cd14588   160 KKLMKACVPSCPST-DPSQTYLRTLEESEWLSQLHKLLQVSVLVVELLDSGSSVLVSLEDGWDITTQVVSLVQLLSDPYY 238

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568993627 1478 RTLEGFRLLVEKEWLSFGHRFSHRGAHTLAGQSSGFTPVFLQFLDCVHQVHLQ 1530
Cdd:cd14588   239 RTIEGFRLLVEKEWLSFGHRFSHRGAQTLASQSSGFTPVFLQFLDCVHQIHLQ 291
SBF2 pfam12335
Myotubularin protein; This domain family is found in eukaryotes, and is approximately 220 ...
 550-772 5.20e-134

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: 416.71  E-value: 5.20e-134
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627   550 GPPMTAILERCSGPHINSARRLEVVRNCISYVFEGKMLEAKKLLPAVLRALKGRAARRCLAHELHLHVQQNRAVLDHQQF 629
Cdd:pfam12335    1 GPPVVSIVDKRGNVFSNSARRLEVLRNCISFIFENKISEARKSLPAVLRALKGKAARLALCEELNQHVQQNRAVLDHQQF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627   630 DFVVRMMNCCLQDCTSLDEHGIASALLPLVTAFCRKLSPGVTQFAYSCVQEHVVWSTPQFWEAMFYGDVQTHIRALYLEP 709
Cdd:pfam12335   81 DLVVRLMNCALQDCSSMDEYGVAAALLPLSTAFCRKLCTGVIQFAYTCVQDHPVWKNQQFWEAAFYQDVQKQIRALYLPS 160

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568993627   710 SDGVSPTQETGE----AQSQDDERSALDVASEQRRLWPTLSREKQQELVQKEESTVFSQAIHYANRM 772
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 ...
 901-1019 4.23e-66

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: 218.96  E-value: 4.23e-66
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627  901 EECVLDGLRVYLLPDGREEGVGGSGGGPALLPAEGAVFLTTYRVIFTGMPTDPLVGEQVVVRSFPVAALTKEKRISVQTP 980
Cdd:cd13340     1 EECVMDGLRVYLLPDGREEASGGSLGGPPLLPAEGAIFLTTYRVIFKGTPTDPLVGEQVVVRSFPVASLTKEKRISVQAQ 80

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 568993627  981 VDQLLQDGLQLRSCTFQLLKMAFDEEVGSDSAELFRKQL 1019
Cdd:cd13340    81 MDQFLQEGLQLRSCTFQLLKIAFDEEVASDSAEVFRKHL 119
PH_Sbf1_hMTMR5 cd01235
Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a ...
 1794-1899 2.35e-63

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: 210.65  E-value: 2.35e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1794 ENRSYEGILYKKGAFMKPWKARWFVLDKTKHQLRYYDHRMDTECKGVIDLAEVEAVAPGTPTIGAPKTVDEKAFFDVKTT 1873
Cdd:cd01235     1 ENRTHEGYLYKRGALLKGWKQRWFVLDSTKHQLRYYESREDTKCKGFIDLAEVESVTPATPIIGAPKRADEGAFFDLKTN 80

                          90       100
                  ....*....|....*....|....*.
gi 568993627 1874 RRVYNFCAQDVPSAQQWVDRIQSCLS 1899
Cdd:cd01235    81 KRVYNFCAFDAESAQQWIEKIQSCLS 106
DENN smart00799
Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN; The ...
 129-318 9.01e-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: 203.58  E-value: 9.01e-60
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627    129 APKTLVLVSRLDHAEVFRNSLGLIYAIHVEGLNVSLENVIgNLLTCTVPLAGGSQldsveegaRTISLGAGDRQVIQTPL 208
Cdd:smart00799    1 APKCICILSRLPFFELFRKILNELYRLLPSSSNLPLELLI-SLLLYPVPPPGGSL--------VLVSLGPGDLIELQRPL 71

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627    209 VDSLPVSRCSVALLFRQLGITNVLSLFCAALTEHKVLFLSRSYQRLADACRGLLALLFPLRYSFTYVPILPAQLLEVLST 288
Cdd:smart00799   72 DSSLPLIDFSLHELFECLGVENILQLFAALLLERRIIFTSSNLSTLSAVIEALLALLYPFVWQHIYIPILPASLLDVLSA 151

                           170       180       190
                    ....*....|....*....|....*....|..
gi 568993627    289 PTPFIIGVNAAFQAETQELL--DVIVADLDGG 318
Cdd:smart00799  152 PTPFIIGVHSSYFEEVKELPdeDVVVVDLDTG 183
uDENN smart00800
Domain always found upstream of DENN domain, found in a variety of signalling proteins; The ...
 1-86 1.35e-28

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: 110.89  E-value: 1.35e-28
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627      1 MARLADYFVLVAFGPHPRGSGEGQ-GQILQRFPEKDWEDNPFPQGIELFCQPSGWQLCP--ERNPPTFFVAVLTDINSER 77
Cdd:smart00800    1 PSRLFDYFVVVGLDSDTGPLGRSYkPEILQRYPEKDFEDFPLPDSIPLFCFPEGLDFVTqtSSKDPQFFSFVLTDIDGSR 80


                    ....*....
gi 568993627     78 HYCACLTFW 86
Cdd:smart00800   81 RYGFCLRFY 89
dDENN smart00801
Domain always found downstream of DENN domain, found in a variety of signalling proteins; The ...
 372-440 4.20e-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: 4.20e-19
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568993627    372 DKELRAVFLRLFAQLLQGYRWCLHIVRIHPEPVIRFHKAAFLGQRGLVEDDFLMKVLEGMAFAGFVSER 440
Cdd:smart00801    1 NDEIREAFLRFFVNLFGGYRNFLRELRKEPGPVITFDKESFLKSRPSSERPFLSKFLETQMFSQFIEER 69
 
Name Accession Description Interval E-value
PTP-MTMR5 cd14588
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1158-1530 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: 573.84  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1158 FRISPVNRMYAICRSYPGLLIVPQSIQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLLRSGGLHGKGVVGLFKAQNTPSP 1237
Cdd:cd14588     1 FRISTVNRMYAVCRSYPGLLIVPQSIQDNTIQRISRCYRQNRFPVVCWRNSRTKAVLLRSGGLHGKGVVGLFKSQNAPAA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1238 GQAQADSSSLEQEKYLQAVVSSMPRYADSSGRNTLSSFssahmgghvpsprarvttlsnplaasasrwtasrgkwssvra 1317
Cdd:cd14588    81 GQSQTDSTSLEQEKYLQAVINSMPRYADASGRNTLSGF------------------------------------------ 118

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1318 sgrssglgsdvgsrlagrdllstphtngappdsgflrpqRAALYIIGDKAQLKGVRPDPLQQWELVPIEVFEARQVKASF 1397
Cdd:cd14588   119 ---------------------------------------RAALYIIGDKSQLKGVKQDPLQQWEVVPIEVFDVRQVKASF 159

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1398 KKLLKACVPGCPATePSPASFLRSLEDSEWLIQIHKLLQISVLVVELLDSGSSVLVSLEDGWDITTQVVSLVQLLSDPFY 1477
Cdd:cd14588   160 KKLMKACVPSCPST-DPSQTYLRTLEESEWLSQLHKLLQVSVLVVELLDSGSSVLVSLEDGWDITTQVVSLVQLLSDPYY 238

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568993627 1478 RTLEGFRLLVEKEWLSFGHRFSHRGAHTLAGQSSGFTPVFLQFLDCVHQVHLQ 1530
Cdd:cd14588   239 RTIEGFRLLVEKEWLSFGHRFSHRGAQTLASQSSGFTPVFLQFLDCVHQIHLQ 291
SBF2 pfam12335
Myotubularin protein; This domain family is found in eukaryotes, and is approximately 220 ...
 550-772 5.20e-134

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: 416.71  E-value: 5.20e-134
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627   550 GPPMTAILERCSGPHINSARRLEVVRNCISYVFEGKMLEAKKLLPAVLRALKGRAARRCLAHELHLHVQQNRAVLDHQQF 629
Cdd:pfam12335    1 GPPVVSIVDKRGNVFSNSARRLEVLRNCISFIFENKISEARKSLPAVLRALKGKAARLALCEELNQHVQQNRAVLDHQQF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627   630 DFVVRMMNCCLQDCTSLDEHGIASALLPLVTAFCRKLSPGVTQFAYSCVQEHVVWSTPQFWEAMFYGDVQTHIRALYLEP 709
Cdd:pfam12335   81 DLVVRLMNCALQDCSSMDEYGVAAALLPLSTAFCRKLCTGVIQFAYTCVQDHPVWKNQQFWEAAFYQDVQKQIRALYLPS 160

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568993627   710 SDGVSPTQETGE----AQSQDDERSALDVASEQRRLWPTLSREKQQELVQKEESTVFSQAIHYANRM 772
Cdd:pfam12335  161 DEKNPHISAQGKntasLASHAEEPSALEIAAEQMRLWPTLSKEKQQELVKSEESTVYSQAIHYANRM 227
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
 1136-1565 4.70e-100

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: 325.20  E-value: 4.70e-100
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627  1136 RDYQRLGLGTlssslsrakSEPFRISPVNRMYAICRSYPGLLIVPQSIQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLL 1215
Cdd:pfam06602   12 AEFARQGLPS---------KDEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHKENGAVIT 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627  1216 RSgglhgkgvvglfkAQntPSPGQAQAdsSSLEQEKYLQAVVSSMPRYAdssgrntlssfssahmgghvpsprarvttls 1295
Cdd:pfam06602   83 RS-------------SQ--PLVGLNGK--RSIEDEKLLQAIFKSSNPYS------------------------------- 114

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627  1296 nplaasasrwtasrgkwssvrasgrssglgsdvgsrlagrdllstphtngapPDSGFLRPQRAALYIIGDKAQLKGVRP- 1374
Cdd:pfam06602  115 ----------------------------------------------------AKKLYIVDARPKLNAMANRAKGGGYENe 142

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627  1375 DPLQQWELVPIEVFEARQVKASFKKLLKACVPgcpaTEPSPASFLRSLEDSEWLIQIHKLLQISVLVVELLDS-GSSVLV 1453
Cdd:pfam06602  143 DNYPNCKKIFLGIENIHVMRDSLNKLVEACND----RSPSMDKWLSRLESSGWLKHIKAILDGACLIAQAVDLeGSSVLV 218

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627  1454 SLEDGWDITTQVVSLVQLLSDPFYRTLEGFRLLVEKEWLSFGHRFSHRGAHTLAGQSSGFT-PVFLQFLDCVHQVHLQFP 1532
Cdd:pfam06602  219 HCSDGWDRTAQLTSLAQLLLDPYYRTIEGFQVLIEKEWLSFGHKFADRCGHLAGFTDSKERsPVFLQFLDCVWQLLRQFP 298

                          410       420       430
                   ....*....|....*....|....*....|...
gi 568993627  1533 MEFEFSQFYLKFLGYHHTSRRFRTFLLDSDYER 1565
Cdd:pfam06602  299 CAFEFNERFLIRLLYHLYSCQFGTFLCNSEKER 331
PH-GRAM_MTMR5 cd13340
Myotubularian (MTM) related 5 protein (MTMR5) Pleckstrin Homology-Glucosyltransferases, ...
 901-1019 4.23e-66

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: 218.96  E-value: 4.23e-66
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627  901 EECVLDGLRVYLLPDGREEGVGGSGGGPALLPAEGAVFLTTYRVIFTGMPTDPLVGEQVVVRSFPVAALTKEKRISVQTP 980
Cdd:cd13340     1 EECVMDGLRVYLLPDGREEASGGSLGGPPLLPAEGAIFLTTYRVIFKGTPTDPLVGEQVVVRSFPVASLTKEKRISVQAQ 80

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 568993627  981 VDQLLQDGLQLRSCTFQLLKMAFDEEVGSDSAELFRKQL 1019
Cdd:cd13340    81 MDQFLQEGLQLRSCTFQLLKIAFDEEVASDSAEVFRKHL 119
PH_Sbf1_hMTMR5 cd01235
Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a ...
 1794-1899 2.35e-63

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: 210.65  E-value: 2.35e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1794 ENRSYEGILYKKGAFMKPWKARWFVLDKTKHQLRYYDHRMDTECKGVIDLAEVEAVAPGTPTIGAPKTVDEKAFFDVKTT 1873
Cdd:cd01235     1 ENRTHEGYLYKRGALLKGWKQRWFVLDSTKHQLRYYESREDTKCKGFIDLAEVESVTPATPIIGAPKRADEGAFFDLKTN 80

                          90       100
                  ....*....|....*....|....*.
gi 568993627 1874 RRVYNFCAQDVPSAQQWVDRIQSCLS 1899
Cdd:cd01235    81 KRVYNFCAFDAESAQQWIEKIQSCLS 106
DENN smart00799
Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN; The ...
 129-318 9.01e-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: 203.58  E-value: 9.01e-60
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627    129 APKTLVLVSRLDHAEVFRNSLGLIYAIHVEGLNVSLENVIgNLLTCTVPLAGGSQldsveegaRTISLGAGDRQVIQTPL 208
Cdd:smart00799    1 APKCICILSRLPFFELFRKILNELYRLLPSSSNLPLELLI-SLLLYPVPPPGGSL--------VLVSLGPGDLIELQRPL 71

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627    209 VDSLPVSRCSVALLFRQLGITNVLSLFCAALTEHKVLFLSRSYQRLADACRGLLALLFPLRYSFTYVPILPAQLLEVLST 288
Cdd:smart00799   72 DSSLPLIDFSLHELFECLGVENILQLFAALLLERRIIFTSSNLSTLSAVIEALLALLYPFVWQHIYIPILPASLLDVLSA 151

                           170       180       190
                    ....*....|....*....|....*....|..
gi 568993627    289 PTPFIIGVNAAFQAETQELL--DVIVADLDGG 318
Cdd:smart00799  152 PTPFIIGVHSSYFEEVKELPdeDVVVVDLDTG 183
DENN pfam02141
DENN (AEX-3) domain; DENN (after differentially expressed in neoplastic vs normal cells) is a ...
 128-318 1.09e-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: 189.32  E-value: 1.09e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627   128 FAPKTLVLVSRLDHAEVFRNSLGLIYAIHVEGLN-VSLENVIGNLLTC-TVPLAGGSQldsveegaRTISLGAGDRQVIQ 205
Cdd:pfam02141    1 RIPKAYCIISRLPFFNLFKKFLDELYRRRTISPLpNPIERFIANLLYEvPFPPPGRTQ--------KLKPLGGTEPILLQ 72

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627   206 TPLVDSLPVSRCSVALLFRQLGITNVLSLFCAALTEHKVLFLSRSYQRLADACRGLLALLFPLRYSFTYVPILPAQLLEV 285
Cdd:pfam02141   73 RPEDSELPLEGVDLHLLFRCLSPENILQLFEAALLERRIIFLSSDLARLTLVAEAVVALLYPFVWQHIYIPVLPASLLDV 152

                          170       180       190
                   ....*....|....*....|....*....|....
gi 568993627   286 LSTPTPFIIGVNAAFQAET-QELLDVIVADLDGG 318
Cdd:pfam02141  153 LSAPTPFIIGVHSRYFDLLeDPLDDVVLVDLDTG 186
uDENN smart00800
Domain always found upstream of DENN domain, found in a variety of signalling proteins; The ...
 1-86 1.35e-28

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: 110.89  E-value: 1.35e-28
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627      1 MARLADYFVLVAFGPHPRGSGEGQ-GQILQRFPEKDWEDNPFPQGIELFCQPSGWQLCP--ERNPPTFFVAVLTDINSER 77
Cdd:smart00800    1 PSRLFDYFVVVGLDSDTGPLGRSYkPEILQRYPEKDFEDFPLPDSIPLFCFPEGLDFVTqtSSKDPQFFSFVLTDIDGSR 80


                    ....*....
gi 568993627     78 HYCACLTFW 86
Cdd:smart00800   81 RYGFCLRFY 89
uDENN pfam03456
uDENN domain; This region is always found associated with pfam02141. It is predicted to form ...
 25-84 2.66e-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: 94.60  E-value: 2.66e-23
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627    25 GQILQRFPEKDWEDNPFPQGIELFCQPSGWQLCPERnPPTFFVAVLTDINSERHYCACLT 84
Cdd:pfam03456    1 PEVLDRYPEDDWSDPPLPDGIPMFCFPEGLETLSSR-EPTFFSFVLTDEDGSRLYGACLT 59
dDENN smart00801
Domain always found downstream of DENN domain, found in a variety of signalling proteins; The ...
 372-440 4.20e-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: 4.20e-19
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568993627    372 DKELRAVFLRLFAQLLQGYRWCLHIVRIHPEPVIRFHKAAFLGQRGLVEDDFLMKVLEGMAFAGFVSER 440
Cdd:smart00801    1 NDEIREAFLRFFVNLFGGYRNFLRELRKEPGPVITFDKESFLKSRPSSERPFLSKFLETQMFSQFIEER 69
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 1798-1899 2.39e-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: 70.66  E-value: 2.39e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627   1798 YEGILYKKGA-FMKPWKARWFVLdkTKHQLRYYDHR---MDTECKGVIDLAEVEAVapgtpTIGAPKTVDEKAFFDVKT- 1872
Cdd:smart00233    3 KEGWLYKKSGgGKKSWKKRYFVL--FNSTLLYYKSKkdkKSYKPKGSIDLSGCTVR-----EAPDPDSSKKPHCFEIKTs 75

                            90       100
                    ....*....|....*....|....*..
gi 568993627   1873 TRRVYNFCAQDVPSAQQWVDRIQSCLS 1899
Cdd:smart00233   76 DRKTLLLQAESEEEREKWVEALRKAIA 102
GRAM pfam02893
GRAM domain; The GRAM domain is found in in glucosyltransferases, myotubularins and other ...
 898-1025 9.04e-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: 69.32  E-value: 9.04e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627   898 LPGEECVLDGLRVYLLPDgreegvggsgggpaLLPAEGAVFLTTYRVIFTGMPTDPLvgeQVVVrsFPVAALtkeKRISV 977
Cdd:pfam02893    9 LPPEERLIASYSCYLNRD--------------GGPVQGRLYLTNYRLCFRSLPKGWS---TKVV--IPLVDI---EEIEK 66

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 568993627   978 QTPVDQLLQDGLQLRSCTFQllKMAFDEEVGSDSAELFRKQLHKLRYP 1025
Cdd:pfam02893   67 LKGGANLFPNGIQVETGSND--KFSFAGFVTRDEAIEFILALLKNAHP 112
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 1798-1899 1.50e-10

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 59.88  E-value: 1.50e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627  1798 YEGILYKKG-AFMKPWKARWFVLdkTKHQLRYYDHRM---DTECKGVIDLAEVEAVapgtpTIGAPKTVDEKAFFDVKTT 1873
Cdd:pfam00169    3 KEGWLLKKGgGKKKSWKKRYFVL--FDGSLLYYKDDKsgkSKEPKGSISLSGCEVV-----EVVASDSPKRKFCFELRTG 75

                           90       100       110
                   ....*....|....*....|....*....|
gi 568993627  1874 ----RRVYNFCAQDVPSAQQWVDRIQSCLS 1899
Cdd:pfam00169   76 ertgKRTYLLQAESEEERKDWIKAIQSAIR 105
GRAM smart00568
domain in glucosyltransferases, myotubularins and other putative membrane-associated proteins;
898-976 7.83e-06

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


Pssm-ID: 214725 [Multi-domain]  Cd Length: 60  Bit Score: 44.89  E-value: 7.83e-06
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568993627    898 LPGEECVLDGLRVYLLpdgreegvggsgggpALLPAEGAVFLTTYRVIFTGMPTDPLvgeqvVVRSFPVAALTKEKRIS 976
Cdd:smart00568    2 LPEEEKLIADYSCYLS---------------RTGPVQGRLYISNYRLCFRSNLPGKL-----TKVVIPLADITRIEKST 60
dDENN pfam03455
dDENN domain; This region is always found associated with pfam02141. It is predicted to form a ...
 407-453 1.37e-05

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: 44.11  E-value: 1.37e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 568993627   407 FHKAAFLGQRGLVEDDFLMKVLEGMAFAGFVSERG-VPYRATDLFDEL 453
Cdd:pfam03455    1 FDKEAFLKSLPSDSRPFLSQFLETQMFNEFIEERLeSSDPSIDLFDEE 48
 
Name Accession Description Interval E-value
PTP-MTMR5 cd14588
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1158-1530 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: 573.84  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1158 FRISPVNRMYAICRSYPGLLIVPQSIQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLLRSGGLHGKGVVGLFKAQNTPSP 1237
Cdd:cd14588     1 FRISTVNRMYAVCRSYPGLLIVPQSIQDNTIQRISRCYRQNRFPVVCWRNSRTKAVLLRSGGLHGKGVVGLFKSQNAPAA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1238 GQAQADSSSLEQEKYLQAVVSSMPRYADSSGRNTLSSFssahmgghvpsprarvttlsnplaasasrwtasrgkwssvra 1317
Cdd:cd14588    81 GQSQTDSTSLEQEKYLQAVINSMPRYADASGRNTLSGF------------------------------------------ 118

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1318 sgrssglgsdvgsrlagrdllstphtngappdsgflrpqRAALYIIGDKAQLKGVRPDPLQQWELVPIEVFEARQVKASF 1397
Cdd:cd14588   119 ---------------------------------------RAALYIIGDKSQLKGVKQDPLQQWEVVPIEVFDVRQVKASF 159

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1398 KKLLKACVPGCPATePSPASFLRSLEDSEWLIQIHKLLQISVLVVELLDSGSSVLVSLEDGWDITTQVVSLVQLLSDPFY 1477
Cdd:cd14588   160 KKLMKACVPSCPST-DPSQTYLRTLEESEWLSQLHKLLQVSVLVVELLDSGSSVLVSLEDGWDITTQVVSLVQLLSDPYY 238

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|...
gi 568993627 1478 RTLEGFRLLVEKEWLSFGHRFSHRGAHTLAGQSSGFTPVFLQFLDCVHQVHLQ 1530
Cdd:cd14588   239 RTIEGFRLLVEKEWLSFGHRFSHRGAQTLASQSSGFTPVFLQFLDCVHQIHLQ 291
PTP-MTMR5-like cd14534
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1158-1530 4.80e-141

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: 438.34  E-value: 4.80e-141
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1158 FRISPVNRMYAICRSYPGLLIVPQSIQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLLRSGGLHGKGVVGLFKAQNTPSP 1237
Cdd:cd14534     1 FRISTANRDYSICRSYPALVVVPQSVSDESLRKVARCYRQGRFPVVTWRHPRTKALLLRSGGFHGKGVMGMLKSANTSTS 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1238 GQA---QADSSSLEQEKYLQAVVssmpryadssgrntlssfssahmgghvpsprarvttlsnplaasasrwtasrgkwss 1314
Cdd:cd14534    81 SPTvssSETSSSLEQEKYLSALV--------------------------------------------------------- 103

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1315 vrasgrssglgsdvgsrlagrdllstphtngappdsgflrpqraaLYIIGDKAQLKGVRPDPLQQWELVPIEVFEARQVK 1394
Cdd:cd14534   104 ---------------------------------------------LYVLGEKSQMKGVKAESDPKCEFIPVEYPEVRQVK 138

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1395 ASFKKLLKACVPGCPATEPSPaSFLRSLEDSEWLIQIHKLLQISVLVVELLD-SGSSVLVSLEDGWDITTQVVSLVQLLS 1473
Cdd:cd14534   139 ASFKKLLRACVPSSAPTEPEQ-SFLKAVEDSEWLQQLQCLMQLSGAVVDLLDvQGSSVLLCLEDGWDVTTQVSSLSQLLL 217

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568993627 1474 DPFYRTLEGFRLLVEKEWLSFGHRFSHRGAHTLAGQSSGFTPVFLQFLDCVHQVHLQ 1530
Cdd:cd14534   218 DPYYRTLEGFRVLVEKEWLAFGHRFSHRSNLTAASQSSGFAPVFLQFLDAVHQIHRQ 274
PTP-MTMR13 cd14589
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1158-1530 2.43e-138

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: 432.04  E-value: 2.43e-138
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1158 FRISPVNRMYAICRSYPGLLIVPQSIQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLLRSGGLHGKGVVGLFKAQNTPSP 1237
Cdd:cd14589     1 FRITAVNRMYSLCRSYPGLLVVPQSVQDSSLQKVARCYRHNRLPVVCWKNSKTKAVLLRSGGFHGKGVVGLFKSQNPHSA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1238 GQAQAD-SSSLEQEKYLQAVVSSMPRYADSSGRNTLssfssahmgghvpsprarvttLSNPLaasasrwtasrgkwssvr 1316
Cdd:cd14589    81 APASSEsSSSIEQEKYLQALLNAISVHQKMNGNSTL---------------------LQSQL------------------ 121

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1317 asgrssglgsdvgsrlagrdllstphtngappdsgfLRPQrAALYIIGDKAQLKGVRPDPLQQWELVPIEVFEARQVKAS 1396
Cdd:cd14589   122 ------------------------------------LKRQ-AALYIFGEKSQLRGFKLDFALNCEFVPVEFHDIRQVKAS 164

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1397 FKKLLKACVPGCPATEPSpASFLRSLEDSEWLIQIHKLLQISVLVVELLDSGSSVLVSLEDGWDITTQVVSLVQLLSDPF 1476
Cdd:cd14589   165 FKKLMRACVPSTIPTDSE-VTFLKALGESEWFLQLHRIMQLAVVISELLESGSSVMVCLEDGWDITTQVVSLVQLLSDPF 243

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568993627 1477 YRTLEGFRLLVEKEWLSFGHRFSHRGAHTLAGQSSGFTPVFLQFLDCVHQVHLQ 1530
Cdd:cd14589   244 YRTLEGFQMLVEKEWLSFGHKFSQRSNLTPNSQGSGFAPIFLQFLDCVHQIHNQ 297
SBF2 pfam12335
Myotubularin protein; This domain family is found in eukaryotes, and is approximately 220 ...
 550-772 5.20e-134

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: 416.71  E-value: 5.20e-134
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627   550 GPPMTAILERCSGPHINSARRLEVVRNCISYVFEGKMLEAKKLLPAVLRALKGRAARRCLAHELHLHVQQNRAVLDHQQF 629
Cdd:pfam12335    1 GPPVVSIVDKRGNVFSNSARRLEVLRNCISFIFENKISEARKSLPAVLRALKGKAARLALCEELNQHVQQNRAVLDHQQF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627   630 DFVVRMMNCCLQDCTSLDEHGIASALLPLVTAFCRKLSPGVTQFAYSCVQEHVVWSTPQFWEAMFYGDVQTHIRALYLEP 709
Cdd:pfam12335   81 DLVVRLMNCALQDCSSMDEYGVAAALLPLSTAFCRKLCTGVIQFAYTCVQDHPVWKNQQFWEAAFYQDVQKQIRALYLPS 160

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 568993627   710 SDGVSPTQETGE----AQSQDDERSALDVASEQRRLWPTLSREKQQELVQKEESTVFSQAIHYANRM 772
Cdd:pfam12335  161 DEKNPHISAQGKntasLASHAEEPSALEIAAEQMRLWPTLSKEKQQELVKSEESTVYSQAIHYANRM 227
Myotub-related pfam06602
Myotubularin-like phosphatase domain; This family represents the phosphatase domain within ...
 1136-1565 4.70e-100

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: 325.20  E-value: 4.70e-100
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627  1136 RDYQRLGLGTlssslsrakSEPFRISPVNRMYAICRSYPGLLIVPQSIQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLL 1215
Cdd:pfam06602   12 AEFARQGLPS---------KDEWRISDINKDYKVCPTYPALLVVPKSISDETLKKAAKFRSKGRIPVLSYRHKENGAVIT 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627  1216 RSgglhgkgvvglfkAQntPSPGQAQAdsSSLEQEKYLQAVVSSMPRYAdssgrntlssfssahmgghvpsprarvttls 1295
Cdd:pfam06602   83 RS-------------SQ--PLVGLNGK--RSIEDEKLLQAIFKSSNPYS------------------------------- 114

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627  1296 nplaasasrwtasrgkwssvrasgrssglgsdvgsrlagrdllstphtngapPDSGFLRPQRAALYIIGDKAQLKGVRP- 1374
Cdd:pfam06602  115 ----------------------------------------------------AKKLYIVDARPKLNAMANRAKGGGYENe 142

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627  1375 DPLQQWELVPIEVFEARQVKASFKKLLKACVPgcpaTEPSPASFLRSLEDSEWLIQIHKLLQISVLVVELLDS-GSSVLV 1453
Cdd:pfam06602  143 DNYPNCKKIFLGIENIHVMRDSLNKLVEACND----RSPSMDKWLSRLESSGWLKHIKAILDGACLIAQAVDLeGSSVLV 218

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627  1454 SLEDGWDITTQVVSLVQLLSDPFYRTLEGFRLLVEKEWLSFGHRFSHRGAHTLAGQSSGFT-PVFLQFLDCVHQVHLQFP 1532
Cdd:pfam06602  219 HCSDGWDRTAQLTSLAQLLLDPYYRTIEGFQVLIEKEWLSFGHKFADRCGHLAGFTDSKERsPVFLQFLDCVWQLLRQFP 298

                          410       420       430
                   ....*....|....*....|....*....|...
gi 568993627  1533 MEFEFSQFYLKFLGYHHTSRRFRTFLLDSDYER 1565
Cdd:pfam06602  299 CAFEFNERFLIRLLYHLYSCQFGTFLCNSEKER 331
PH-GRAM_MTMR5 cd13340
Myotubularian (MTM) related 5 protein (MTMR5) Pleckstrin Homology-Glucosyltransferases, ...
 901-1019 4.23e-66

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: 218.96  E-value: 4.23e-66
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627  901 EECVLDGLRVYLLPDGREEGVGGSGGGPALLPAEGAVFLTTYRVIFTGMPTDPLVGEQVVVRSFPVAALTKEKRISVQTP 980
Cdd:cd13340     1 EECVMDGLRVYLLPDGREEASGGSLGGPPLLPAEGAIFLTTYRVIFKGTPTDPLVGEQVVVRSFPVASLTKEKRISVQAQ 80

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 568993627  981 VDQLLQDGLQLRSCTFQLLKMAFDEEVGSDSAELFRKQL 1019
Cdd:cd13340    81 MDQFLQEGLQLRSCTFQLLKIAFDEEVASDSAEVFRKHL 119
PH_Sbf1_hMTMR5 cd01235
Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a ...
 1794-1899 2.35e-63

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: 210.65  E-value: 2.35e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1794 ENRSYEGILYKKGAFMKPWKARWFVLDKTKHQLRYYDHRMDTECKGVIDLAEVEAVAPGTPTIGAPKTVDEKAFFDVKTT 1873
Cdd:cd01235     1 ENRTHEGYLYKRGALLKGWKQRWFVLDSTKHQLRYYESREDTKCKGFIDLAEVESVTPATPIIGAPKRADEGAFFDLKTN 80

                          90       100
                  ....*....|....*....|....*.
gi 568993627 1874 RRVYNFCAQDVPSAQQWVDRIQSCLS 1899
Cdd:cd01235    81 KRVYNFCAFDAESAQQWIEKIQSCLS 106
DENN smart00799
Domain found in a variety of signalling proteins, always encircled by uDENN and dDENN; The ...
 129-318 9.01e-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: 203.58  E-value: 9.01e-60
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627    129 APKTLVLVSRLDHAEVFRNSLGLIYAIHVEGLNVSLENVIgNLLTCTVPLAGGSQldsveegaRTISLGAGDRQVIQTPL 208
Cdd:smart00799    1 APKCICILSRLPFFELFRKILNELYRLLPSSSNLPLELLI-SLLLYPVPPPGGSL--------VLVSLGPGDLIELQRPL 71

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627    209 VDSLPVSRCSVALLFRQLGITNVLSLFCAALTEHKVLFLSRSYQRLADACRGLLALLFPLRYSFTYVPILPAQLLEVLST 288
Cdd:smart00799   72 DSSLPLIDFSLHELFECLGVENILQLFAALLLERRIIFTSSNLSTLSAVIEALLALLYPFVWQHIYIPILPASLLDVLSA 151

                           170       180       190
                    ....*....|....*....|....*....|..
gi 568993627    289 PTPFIIGVNAAFQAETQELL--DVIVADLDGG 318
Cdd:smart00799  152 PTPFIIGVHSSYFEEVKELPdeDVVVVDLDTG 183
PH-GRAM_MTMR5_MTMR13 cd13208
Myotubularian (MTM) related 5 and 13 proteins (MTMR5 and MTMR13) Pleckstrin ...
 901-1019 3.58e-56

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: 190.64  E-value: 3.58e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627  901 EECVLDGLRVYLLPDGREEGVGGSGGgPALLPAEGAVFLTTYRVIFTGMPTDPLVGEQVVVRSFPVAALTKEKRISVQTP 980
Cdd:cd13208     1 EELVMEGLRVYLLPDGREEGTGGNGG-PNLLPAEGALFLTNYRVIFKGTPCDPLACEQTVVRSFPIASLTKEKKIAVQKL 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 568993627  981 --VDQLLQDGLQLRSCTFQLLKMAFDEEVGSDSAELFRKQL 1019
Cdd:cd13208    80 ahLDQKLQEGLQLRSATFQLIKVAFDEEVSSEKIEKFRKQL 120
PTP-MTM-like cd14507
protein tyrosine phosphatase-like domain of myotubularins; Myotubularins are a unique subgroup ...
 1198-1526 3.54e-55

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: 191.99  E-value: 3.54e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1198 NRFPVVCWRSGRSKAVLLRSGGLHgkgvVGLFkaqntpspgqaqaDSSSLEQEKYLQAVVSSmpryadSSGRNTLSSFss 1277
Cdd:cd14507     1 GRIPVLSWRHPRNGAVICRSSQPL----VGLT-------------GSRSKEDEKLLNAIRKA------SPSSKKLYIV-- 55

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1278 ahmgghvpsprarvttlsnplaasasrwtasrgkwssvrasgrssglgsdvgsrlagrdllstphtngappDSgflRPQR 1357
Cdd:cd14507    56 -----------------------------------------------------------------------DA---RPKL 61

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1358 AALyiiGDKAQLKGVR-PDPLQQWELVPIEVFEARQVKASFKKLLKACVPGcpatEPSPASFLRSLEDSEWLIQIHKLLQ 1436
Cdd:cd14507    62 NAV---ANRAKGGGYEnTEYYPNCELEFLNIENIHAMRDSLNKLRDACLSP----NDEESNWLSALESSGWLEHIRLILK 134

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1437 ISVLVVELLDS-GSSVLVSLEDGWDITTQVVSLVQLLSDPFYRTLEGFRLLVEKEWLSFGHRFSHRGAHTLAGQSSG-FT 1514
Cdd:cd14507   135 GAVRVADLLEKeGTSVLVHCSDGWDRTSQLTSLAQLLLDPYYRTIEGFQVLIEKEWLSFGHKFADRCGHGDKNSSDEeRS 214

                         330
                  ....*....|..
gi 568993627 1515 PVFLQFLDCVHQ 1526
Cdd:cd14507   215 PIFLQFLDCVWQ 226
DENN pfam02141
DENN (AEX-3) domain; DENN (after differentially expressed in neoplastic vs normal cells) is a ...
 128-318 1.09e-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: 189.32  E-value: 1.09e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627   128 FAPKTLVLVSRLDHAEVFRNSLGLIYAIHVEGLN-VSLENVIGNLLTC-TVPLAGGSQldsveegaRTISLGAGDRQVIQ 205
Cdd:pfam02141    1 RIPKAYCIISRLPFFNLFKKFLDELYRRRTISPLpNPIERFIANLLYEvPFPPPGRTQ--------KLKPLGGTEPILLQ 72

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627   206 TPLVDSLPVSRCSVALLFRQLGITNVLSLFCAALTEHKVLFLSRSYQRLADACRGLLALLFPLRYSFTYVPILPAQLLEV 285
Cdd:pfam02141   73 RPEDSELPLEGVDLHLLFRCLSPENILQLFEAALLERRIIFLSSDLARLTLVAEAVVALLYPFVWQHIYIPVLPASLLDV 152

                          170       180       190
                   ....*....|....*....|....*....|....
gi 568993627   286 LSTPTPFIIGVNAAFQAET-QELLDVIVADLDGG 318
Cdd:pfam02141  153 LSAPTPFIIGVHSRYFDLLeDPLDDVVLVDLDTG 186
PTP-MTMR6-like cd14532
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases ...
 1137-1542 3.34e-52

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: 186.39  E-value: 3.34e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1137 DYQRLGLgtlssslsraKSEPFRISPVNRMYAICRSYPGLLIVPQSIQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLLR 1216
Cdd:cd14532     4 EYTRMGV----------PNDNWTLSDINKDYELCDTYPRELFVPTSASTPVLVGSSKFRSKGRLPVLSYLHKDNQAAICR 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1217 -SGGLHGkgvvglFKAQntpspgqaqadssSLEQEKYLQAVVSSMPryadssgrntlssfSSAHMggHVPSPRARVTTLS 1295
Cdd:cd14532    74 cSQPLSG------FSAR-------------CVEDEQLLQAIRKANP--------------NSKFM--YVVDTRPKINAMA 118

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1296 NplaasasrwtasrgkwssvRASGRssglgsdvgsrlagrdllstphtngappdsGFlrpqraalyiiGDKAQLKGVRpd 1375
Cdd:cd14532   119 N-------------------KAAGK------------------------------GY-----------ENEDNYSNIK-- 136

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1376 plqqWELVPIEVFEArqVKASFKKLLKACvpgcPATEPSPASFLRSLEDSEWLIQIHKLLQISVLVVELLDSGSSVLVSL 1455
Cdd:cd14532   137 ----FQFFGIENIHV--MRSSLQKLLEVC----ELKNPSMSAFLSGLESSGWLKHIKAVMDTSVFIAKAVSEGASVLVHC 206

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1456 EDGWDITTQVVSLVQLLSDPFYRTLEGFRLLVEKEWLSFGHRFSHRGAHtLAGQSSGFTPVFLQFLDCVHQVHLQFPMEF 1535
Cdd:cd14532   207 SDGWDRTAQTCSLASLLLDPYYRTIKGFQVLIEKEWLSFGHKFTDRCGH-LQGDAKEVSPVFTQFLDCVWQLMQQFPRAF 285


                  ....*..
gi 568993627 1536 EFSQFYL 1542
Cdd:cd14532   286 EFNERFL 292
PH-GRAM_MTMR13 cd13339
Myotubularian (MTM) related 13 protein Pleckstrin Homology-Glucosyltransferases, Rab-like ...
 901-1019 3.47e-45

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: 159.37  E-value: 3.47e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627  901 EECVLDGLRVYLLPDGREEGVGGSGGGPALLPAEGAVFLTTYRVIFTGMPTDPLVGEQVVVRSFPVAALTKEKRISVQTP 980
Cdd:cd13339     1 EEFVCEGLRVLLDPDGREEATGGLLGGPHILPAEGALFLTTYRIIFKGTPHDQLVGEQTVIRSFPIASITKEKKITIQNQ 80

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 568993627  981 VDQLLQDGLQLRSCTFQLLKMAFDEEVGSDSAELFRKQL 1019
Cdd:cd13339    81 LQQNMQEGLQITSASFQLIKVAFDEEVSPEVVEIFKKQL 119
PTP-MTMR3 cd14586
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1158-1526 1.12e-42

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: 159.42  E-value: 1.12e-42
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1158 FRISPVNRMYAICRSYPGLLIVPQSIQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLLRSGglhgkgvvglfkaqntpSP 1237
Cdd:cd14586     8 WRISNINEKYKLCGSYPQELIVPAWITDKELESVASFRSWKRIPAVVYRHQSNGAVIARCG-----------------QP 70

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1238 GQAQADSSSLEQEKYLQAVVSSMPryADSSgrntlssfSSAHMGGHVPSPRARVTtlsnplaasasrwtasrgkwssvra 1317
Cdd:cd14586    71 EVSWWGWRNADDEHLVQSVAKACA--SDSS--------SCKSVLMTGNCSRDFPN------------------------- 115

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1318 sgrssglgsdvGSRLAGRDLLSTpHTNGAPPDSGFLRPQ-------RAALYIIGDKAQLKGVR-PDPLQQWELVPIEVFE 1389
Cdd:cd14586   116 -----------GGDLSDVEFDSS-MSNASGVESLAIQPQkllildaRSYAAAVANRAKGGGCEcPEYYPNCEVVFMGMAN 183

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1390 ARQVKASFKKLLKACvpgcpATEPSPASFLRSLEDSEWLIQIHKLLQISVLVVELLDSGSS-VLVSLEDGWDITTQVVSL 1468
Cdd:cd14586   184 IHSIRKSFQSLRLLC-----TQMPDPANWLSALESTKWLQHLSMLLKSALLVVHAVDRDQRpVLVHCSDGWDRTPQIVAL 258

                         330       340       350       360       370       380
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 568993627 1469 VQLLSDPFYRTLEGFRLLVEKEWLSFGHRFSHRGAHtlaGQSSG----FTPVFLQFLDCVHQ 1526
Cdd:cd14586   259 SKLLLDPYYRTIEGFQVLVETEWLDFGHKFADRCGH---GENSDdlneRCPVFLQWLDCVHQ 317
PTP-MTMR4 cd14587
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1158-1526 1.33e-40

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: 153.26  E-value: 1.33e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1158 FRISPVNRMYAICRSYPGLLIVPQSIQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLLRSgglhgkgvvglfkaqntpsp 1237
Cdd:cd14587     3 WRVSEINSNYKLCSSYPQKLLVPVWITDKELENVASFRSWKRIPVVVYRHLRNGAVIARC-------------------- 62

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1238 gqaqadsssleqekylqavvsSMPRYADSSGRNTLSSFssahmgghvpspraRVTTLSNPLAASASrwtasrgkwssVRA 1317
Cdd:cd14587    63 ---------------------SQPEISWWGWRNADDEY--------------LVTSIAKACALDPG-----------TRA 96

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1318 SGRSSGLGSDVGSRLAGRDLLST-----PHTNGAPPDSGFLRPQRAALYIIGDKAQLKGVRPDPL-QQWELVPIEVFEAR 1391
Cdd:cd14587    97 PGGSPSKGNSDGSDASDTDFDSSltacsAVESGAAPQKLLILDARSYTAAVANRAKGGGCECEEYyPNCEVMFMGMANIH 176

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1392 QVKASFKKLLKACvpgcpATEPSPASFLRSLEDSEWLIQIHKLLQISVLVVELLD-SGSSVLVSLEDGWDITTQVVSLVQ 1470
Cdd:cd14587   177 SIRNSFQYLRAVC-----SQMPDPGNWLSALESTKWLQHLSVMLKAAVLVASAVDrEGRPVLVHCSDGWDRTPQIVALAK 251

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568993627 1471 LLSDPFYRTLEGFRLLVEKEWLSFGHRFSHRGAHTLAGQS-SGFTPVFLQFLDCVHQ 1526
Cdd:cd14587   252 ILLDPYYRTIEGFQVLVETDWLDFGHKFGDRCGHQENVEDqNEQCPVFLQWLDCVHQ 308
PTP-MTMR7 cd14583
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1137-1548 5.06e-40

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: 151.27  E-value: 5.06e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1137 DYQRLGLgtlssslsraKSEPFRISPVNRMYAICRSYPGLLIVPQSIQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLLR 1216
Cdd:cd14583     4 EYNRMGL----------PNSLWQVSDVNRDYRVCDTYPTELYVPKSATAPIIVGSSKFRSRGRFPVLSYYCKDNNASICR 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1217 SgglhgkgvvglfkaqNTPSPGQAqadSSSLEQEKYLQAVVSSMPryadssgrntlssfSSAHMggHVPSPRARVTTLSN 1296
Cdd:cd14583    74 S---------------SQPLSGFS---ARCLEDEQMLQAIRKANP--------------GSDFM--YVVDTRPKLNAMAN 119

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1297 plaasasrwtasrgkwssvRASGRssglgsdvgsrlagrdllstphtnGAPPDSGFlrpqraalyiigdkAQLKgvrpdp 1376
Cdd:cd14583   120 -------------------RAAGK------------------------GYENEDNY--------------SNIK------ 136

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1377 lqqWELVPIEVFEArqVKASFKKLLKACvpgcPATEPSPASFLRSLEDSEWLIQIHKLLQISVLVVELL-DSGSSVLVSL 1455
Cdd:cd14583   137 ---FQFIGIENIHV--MRNSLQKMLEVC----ELRSPSMGDFLWGLENSGWLKHIKAIMDAGIFIAKAVaEEGASVLVHC 207

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1456 EDGWDITTQVVSLVQLLSDPFYRTLEGFRLLVEKEWLSFGHRFSHRGAHtLAGQSSGFTPVFLQFLDCVHQVHLQFPMEF 1535
Cdd:cd14583   208 SDGWDRTAQVCSVASLLLDPYYRTIKGFMVLIEKDWVSFGHKFNHRYGH-LDGDPKEVSPVIDQFIECVWQLMEQFPCAF 286

                         410
                  ....*....|...
gi 568993627 1536 EFSQFYLKFLGYH 1548
Cdd:cd14583   287 EFNERFLIHIHHH 299
PTP-MTMR8 cd14584
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1137-1542 8.52e-39

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: 148.10  E-value: 8.52e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1137 DYQRLGLgtlssslsraKSEPFRISPVNRMYAICRSYPGLLIVPQSIQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLLR 1216
Cdd:cd14584    10 DFQRMGI----------PNDYWEITDANKNYEICSTYPPELVVPKSASKATVVGSSKFRSRGRFPVLSYLYKENNAAICR 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1217 -SGGLHGkgvvglFKAQntpspgqaqadssSLEQEKYLQAVVSSMPryadssgrntlssfSSAHMggHVPSPRARVTTLS 1295
Cdd:cd14584    80 cSQPLSG------FSAR-------------CVEDEQMLQAISKANP--------------GSPFM--YVVDTRPKLNAMA 124

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1296 NplaASASRWTASRGKWSSVRasgrssglgsdvgsrlagrdllstphtngappdsgflrpqraalyiigdkaqlkgvrpd 1375
Cdd:cd14584   125 N---RAAGKGYENEDNYSNIR----------------------------------------------------------- 142

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1376 plqqWELVPIEVFEArqVKASFKKLLKACvpgcPATEPSPASFLRSLEDSEWLIQIHKLLQISVLVVELL-DSGSSVLVS 1454
Cdd:cd14584   143 ----FQFIGIENIHV--MRSSLQKLLEVC----EMKSPSMSDFLTGLENSGWLRHIKAVMDAGVFLAKAVkEEKASVLVH 212

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1455 LEDGWDITTQVVSLVQLLSDPFYRTLEGFRLLVEKEWLSFGHRFSHRGAHtLAGQSSGFTPVFLQFLDCVHQVHLQFPME 1534
Cdd:cd14584   213 CSDGWDRTAQVCSLASLLLDPFYRTIKGLMVLIEKEWISMGHKFSQRCGH-LDGDPKEVSPVFTQFLECVWQLMEQFPCA 291


                  ....*...
gi 568993627 1535 FEFSQFYL 1542
Cdd:cd14584   292 FEFNEHFL 299
PTP-MTM1-like cd14535
protein tyrosine phosphatase-like domain of myotubularin, and myotubularin related ...
 1354-1542 1.63e-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: 145.28  E-value: 1.63e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1354 RPQRAAlyiIGDKAQLKGV-RPDPLQQWELVPIEVFEARQVKASFKKLLKACVPGCPATEpspasFLRSLEDSEWLIQIH 1432
Cdd:cd14535    58 RPSVNA---VANKAKGGGYeSEDAYQNAELVFLDIHNIHVMRESLRKLKDICFPNIDDSH-----WLSNLESTHWLEHIK 129

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1433 KLLQISVLVVELLDSG-SSVLVSLEDGWDITTQVVSLVQLLSDPFYRTLEGFRLLVEKEWLSFGHRFSHRGAHTLAGQS- 1510
Cdd:cd14535   130 LILAGAVRIADKVESGkTSVVVHCSDGWDRTAQLTSLAMLMLDPYYRTIRGFEVLIEKEWLSFGHKFAQRIGHGDKNHSd 209

                         170       180       190
                  ....*....|....*....|....*....|..
gi 568993627 1511 SGFTPVFLQFLDCVHQVHLQFPMEFEFSQFYL 1542
Cdd:cd14535   210 ADRSPVFLQFIDCVWQMTRQFPNAFEFNEHFL 241
PTP-MTMR3-like cd14533
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatases ...
 1393-1526 2.88e-37

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: 140.62  E-value: 2.88e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1393 VKASFKKLLKACvpgcpATEPSPASFLRSLEDSEWLIQIHKLLQISVLVVELLD-SGSSVLVSLEDGWDITTQVVSLVQL 1471
Cdd:cd14533    99 IRKSFHSLRALC-----SSAPDQPNWLSNLESTKWLHHLSGLLKAALLVVNAVDeEGRPVLVHCSDGWDRTPQIVALAEL 173

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568993627 1472 LSDPFYRTLEGFRLLVEKEWLSFGHRFSHRGAHTL-AGQSSGFTPVFLQFLDCVHQ 1526
Cdd:cd14533   174 MLDPYYRTIEGFQVLVEREWLDFGHKFADRCGHGVnSEDINERCPVFLQWLDCVHQ 229
PTP-MTMR6 cd14585
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1137-1542 4.00e-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: 142.76  E-value: 4.00e-37
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1137 DYQRLGLgtlssslsraKSEPFRISPVNRMYAICRSYPGLLIVPQSIQDNALQRVSRCYRQNRFPVVCWRSGRSKAVLLR 1216
Cdd:cd14585     4 EYKRMGV----------PNDYWQLSDVNRDYKICDTYPRDLYVPITASKPIIVGSSKFRSKGRFPVLSYYHQEKKAAICR 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1217 -SGGLHGkgvvglFKAQntpspgqaqadssSLEQEKYLQAVVSSMPryadssgrntlssfSSAHMggHVPSPRARVTTLS 1295
Cdd:cd14585    74 cSQPLSG------FSAR-------------CLEDEHMLQAISKANP--------------NNRYM--YVMDTRPKLNAMA 118

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1296 NplaASASRWTASRGKWSSVRasgrssglgsdvgsrlagrdllstphtngappdsgflrpqraalyiigdkaqlkgvrpd 1375
Cdd:cd14585   119 N---RAAGKGYENEDNYSNIR----------------------------------------------------------- 136

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1376 plqqWELVPIEVFEArqVKASFKKLLKACvpGCPATepSPASFLRSLEDSEWLIQIHKLLQISVLVVELL-DSGSSVLVS 1454
Cdd:cd14585   137 ----FQFVGIENIHV--MRSSLQKLLEVC--GTKAL--SVNDFLSGLESSGWLRHIKAVLDAAVFLAKAVaVEGASVLVH 206

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1455 LEDGWDITTQVVSLVQLLSDPFYRTLEGFRLLVEKEWLSFGHRFSHRGAHtLAGQSSGFTPVFLQFLDCVHQVHLQFPME 1534
Cdd:cd14585   207 CSDGWDRTAQVCSLGSLLLDPYYRTIKGFMVLIEKDWISFGHKFSDRCGQ-LDGDPKEISPVFTQFLECVWQLTEQFPRA 285


                  ....*...
gi 568993627 1535 FEFSQFYL 1542
Cdd:cd14585   286 FEFSEAFL 293
PTP-MTMR2 cd14590
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1352-1542 4.11e-36

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: 138.63  E-value: 4.11e-36
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1352 FLRPQRAALYIIGDKAQLKGVRP-DPLQQWELVPIEVFEARQVKASFKKLLKACVPGCpatepSPASFLRSLEDSEWLIQ 1430
Cdd:cd14590    66 FIFDARPSVNAVANKAKGGGYESeDAYQNAELVFLDIHNIHVMRESLRKLKEIVYPNI-----EESHWLSNLESTHWLEH 140

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1431 IHKLLQISVLVVELLDSG-SSVLVSLEDGWDITTQVVSLVQLLSDPFYRTLEGFRLLVEKEWLSFGHRFSHRGAHTLAGQ 1509
Cdd:cd14590   141 IKLILAGALRIADKVESGkTSVVVHCSDGWDRTAQLTSLAMLMLDGYYRTIRGFEVLVEKEWLSFGHRFQLRVGHGDKNH 220

                         170       180       190
                  ....*....|....*....|....*....|....
gi 568993627 1510 S-SGFTPVFLQFLDCVHQVHLQFPMEFEFSQFYL 1542
Cdd:cd14590   221 AdADRSPVFLQFIDCVWQMTRQFPTAFEFNEYFL 254
PTP-MTM1 cd14591
protein tyrosine phosphatase-like domain of myotubularin phosphoinositide phosphatase 1; ...
 1375-1542 1.00e-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: 137.08  E-value: 1.00e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1375 DPLQQWELVPIEVFEARQVKASFKKLLKACVPGCPATEpspasFLRSLEDSEWLIQIHKLLQISVLVVELLDSG-SSVLV 1453
Cdd:cd14591    77 DAYQNAELVFLDIHNIHVMRESLKKLKDIVYPNVEESH-----WLSSLESTHWLEHIKLVLTGAIQVADKVSSGkSSVLV 151

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1454 SLEDGWDITTQVVSLVQLLSDPFYRTLEGFRLLVEKEWLSFGHRFSHRGAHTLAGQS-SGFTPVFLQFLDCVHQVHLQFP 1532
Cdd:cd14591   152 HCSDGWDRTAQLTSLAMLMLDSYYRTIEGFEVLVQKEWISFGHKFASRIGHGDKNHAdADRSPIFLQFIDCVWQMSKQFP 231

                         170
                  ....*....|
gi 568993627 1533 MEFEFSQFYL 1542
Cdd:cd14591   232 TAFEFNEQFL 241
PTP-MTM-like_fungal cd17666
protein tyrosine phosphatase-like domain of fungal myotubularins; Myotubularins are a unique ...
 1412-1526 1.94e-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: 132.57  E-value: 1.94e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1412 EPSPASFLRSLEDSEWLIQIHKLLQISVLVVELLD-SGSSVLVSLEDGWDITTQVVSLVQLLSDPFYRTLEGFRLLVEKE 1490
Cdd:cd17666   120 NPSYPPLINALKKSNWLKYLAIILQGADLIAKSIHfNHSHVLIHCSDGWDRTSQLSALAQLCLDPYYRTLEGFMVLVEKD 199

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 568993627 1491 WLSFGHRFSHRGAHTLAgqssgfTPVFLQFLDCVHQ 1526
Cdd:cd17666   200 WLSFGHRFAERSGHKET------SPVFHQFLDCVYQ 229
PTP-MTMR1 cd14592
protein tyrosine phosphatase-like domain of myotubularin related phosphoinositide phosphatase ...
 1381-1542 7.72e-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: 7.72e-34
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1381 ELVPIEVFEARQVKASFKKLLKACVPGCpatepSPASFLRSLEDSEWLIQIHKLLQISVLVVELLDSG-SSVLVSLEDGW 1459
Cdd:cd14592    83 ELVFLEIHNIHVMRESLRKLKEIVYPSI-----DEARWLSNVDGTHWLEYIRMLLAGAVRIADKIESGkTSVVVHCSDGW 157

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1460 DITTQVVSLVQLLSDPFYRTLEGFRLLVEKEWLSFGHRFSHRGAHTLAGQS-SGFTPVFLQFLDCVHQVHLQFPMEFEFS 1538
Cdd:cd14592   158 DRTAQLTSLAMLMLDSYYRTIKGFEVLIEKEWISFGHRFALRVGHGDDNHAdADRSPIFLQFIDCVWQMTRQFPSAFEFN 237


                  ....
gi 568993627 1539 QFYL 1542
Cdd:cd14592   238 ELFL 241
uDENN smart00800
Domain always found upstream of DENN domain, found in a variety of signalling proteins; The ...
 1-86 1.35e-28

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: 110.89  E-value: 1.35e-28
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627      1 MARLADYFVLVAFGPHPRGSGEGQ-GQILQRFPEKDWEDNPFPQGIELFCQPSGWQLCP--ERNPPTFFVAVLTDINSER 77
Cdd:smart00800    1 PSRLFDYFVVVGLDSDTGPLGRSYkPEILQRYPEKDFEDFPLPDSIPLFCFPEGLDFVTqtSSKDPQFFSFVLTDIDGSR 80


                    ....*....
gi 568993627     78 HYCACLTFW 86
Cdd:smart00800   81 RYGFCLRFY 89
PTP-MTMR10-like cd14537
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1390-1526 6.55e-26

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: 107.04  E-value: 6.55e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1390 ARQVKASFKKLLKACVPGCP-ATEPSPASFLRSLEDSEWLIQIHKLLQISVLVVELL-DSGSSVLVSLEDGWDITTQVVS 1467
Cdd:cd14537    61 LQDVQAAYLKLRELCTPDSSeQFWVQDSKWYSLLENTKWLHYVSACLKKASEAAEALeSRGRSVVLQESDGRDLSCVVSS 140

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1468 LVQLLSDPFYRTLEGFRLLVEKEWLSFGHRFSHRGAHTLAGQ-SSGFTPVFLQFLDCVHQ 1526
Cdd:cd14537   141 LVQLLLDPHFRTITGFQSLIQKEWVALGHPFCDRLGHVKPNKtESEESPVFLLFLDCVWQ 200
PTP-MTMR9 cd14536
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1379-1526 6.79e-26

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: 107.81  E-value: 6.79e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1379 QWELV--PIEVFEARQvkASFKKLLKACV-PGCpatepSPASFLRSLEDSEWLIQIHKLLQISVLVVELLDS-GSSVLVS 1454
Cdd:cd14536    78 QWRRIhkPIERYNVLQ--ESLIKLVEACNdQGH-----SMDKWLSKLESSNWLSHVKEILTTACLVAQCIDReGASVLVH 150

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568993627 1455 LEDGWDITTQVVSLVQLLSDPFYRTLEGFRLLVEKEWLSFGHRFSHRGAHTLAGQSSGFT--PVFLQFLDCVHQ 1526
Cdd:cd14536   151 GSEGMDSTLQVTSLAQIILDPDCRTIRGFEALIEREWLQAGHPFQSRCAKSAYSNSKQKFesPVFLLFLDCVWQ 224
uDENN pfam03456
uDENN domain; This region is always found associated with pfam02141. It is predicted to form ...
 25-84 2.66e-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: 94.60  E-value: 2.66e-23
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627    25 GQILQRFPEKDWEDNPFPQGIELFCQPSGWQLCPERnPPTFFVAVLTDINSERHYCACLT 84
Cdd:pfam03456    1 PEVLDRYPEDDWSDPPLPDGIPMFCFPEGLETLSSR-EPTFFSFVLTDEDGSRLYGACLT 59
PTP-MTMR10 cd14593
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1391-1526 1.20e-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: 94.57  E-value: 1.20e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1391 RQVKASFKKLLKACVPgcPATEPSPASFLRSLEDSEWLIQIHKLLQISVLVVELLDSGS-SVLVSLEDGWDITTQVVSLV 1469
Cdd:cd14593    62 QEIQAAFVKLKQLCVN--EPFEETEEKWLSSLESTRWLEYVRAFLKHSAELVYMLESKHvSVILQEEEGRDLSCVVASLV 139

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 568993627 1470 QLLSDPFYRTLEGFRLLVEKEWLSFGHRFSHRGAHtLAGQSSGFTPVFLQFLDCVHQ 1526
Cdd:cd14593   140 QVMLDPYFRTITGFQSLIQKEWVMAGYRFLDRCNH-LKKSSKKESPLFLLFLDCVWQ 195
PTP-MTMR12 cd14594
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1419-1527 5.96e-21

protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related phosphoinositide phosphatase 12; Myotubularin related phosphoinositide phosphatase 12 (MTMR12), also called phosphatidylinositol 3 phosphate 3-phosphatase adapter subunit (3-PAP), is enzymatically inactive and contains a C-terminal coiled-coil domain and an N-terminal PH-GRAM domain. In general, myotubularins are a unique subgroup of protein tyrosine phosphatases that use inositol phospholipids, rather than phosphoproteins, as substrates. MTMR12 is a pseudophosphatase that lacks the catalytic cysteine in its catalytic pocket. It functions as an adapter for the catalytically active myotubularin to regulate its intracellular location.


Pssm-ID: 350442  Cd Length: 203  Bit Score: 92.98  E-value: 5.96e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1419 LRSLEDSEWLIQIHKLLQISVLVVELLDS-GSSVLVSLEDGWDITTQVVSLVQLLSDPFYRTLEGFRLLVEKEWLSFGHR 1497
Cdd:cd14594    95 FSSLESSNWLEIIRQCLKKAVEVVECLEKqNTNVLLTEEEATDLCCVISSLVQIMMDPYCRTKSGFQSLIQKEWVMGGHC 174

                          90       100       110
                  ....*....|....*....|....*....|
gi 568993627 1498 FSHRGAHtLAGQSSGFTPVFLQFLDCVHQV 1527
Cdd:cd14594   175 FLDRCNH-LRQNDKEEVPVFLLFLDCVWQL 203
dDENN smart00801
Domain always found downstream of DENN domain, found in a variety of signalling proteins; The ...
 372-440 4.20e-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: 4.20e-19
                            10        20        30        40        50        60
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568993627    372 DKELRAVFLRLFAQLLQGYRWCLHIVRIHPEPVIRFHKAAFLGQRGLVEDDFLMKVLEGMAFAGFVSER 440
Cdd:smart00801    1 NDEIREAFLRFFVNLFGGYRNFLRELRKEPGPVITFDKESFLKSRPSSERPFLSKFLETQMFSQFIEER 69
PTP-MTMR11 cd14595
protein tyrosine phosphatase-like pseudophosphatase domain of myotubularin related ...
 1393-1527 7.02e-19

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: 86.81  E-value: 7.02e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1393 VKASFKKLLKACVPGcPATEPSPASFLRSLEDSEWLIQIHKLLQISVLVVELLDSGS-SVLVSLEDGWDITTQVVSLVQL 1471
Cdd:cd14595    62 IQLAYLKLRTLCLPD-ISVSVSDEKWLSNLEGTRWLDHVRACLRKASEVSCLLAERHrSVILQESEDRDLNCLLSSLVQL 140

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 568993627 1472 LSDPFYRTLEGFRLLVEKEWLSFGHRFSHRgAHTLAGQSSGFTPVFLQFLDCVHQV 1527
Cdd:cd14595   141 LSDPHARTISGFQSLVQKEWVVAGHPFLQR-LNLTRESDKEESPVFLLFLDCVWQL 195
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 1798-1899 2.39e-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: 70.66  E-value: 2.39e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627   1798 YEGILYKKGA-FMKPWKARWFVLdkTKHQLRYYDHR---MDTECKGVIDLAEVEAVapgtpTIGAPKTVDEKAFFDVKT- 1872
Cdd:smart00233    3 KEGWLYKKSGgGKKSWKKRYFVL--FNSTLLYYKSKkdkKSYKPKGSIDLSGCTVR-----EAPDPDSSKKPHCFEIKTs 75

                            90       100
                    ....*....|....*....|....*..
gi 568993627   1873 TRRVYNFCAQDVPSAQQWVDRIQSCLS 1899
Cdd:smart00233   76 DRKTLLLQAESEEEREKWVEALRKAIA 102
GRAM pfam02893
GRAM domain; The GRAM domain is found in in glucosyltransferases, myotubularins and other ...
 898-1025 9.04e-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: 69.32  E-value: 9.04e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627   898 LPGEECVLDGLRVYLLPDgreegvggsgggpaLLPAEGAVFLTTYRVIFTGMPTDPLvgeQVVVrsFPVAALtkeKRISV 977
Cdd:pfam02893    9 LPPEERLIASYSCYLNRD--------------GGPVQGRLYLTNYRLCFRSLPKGWS---TKVV--IPLVDI---EEIEK 66

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 568993627   978 QTPVDQLLQDGLQLRSCTFQllKMAFDEEVGSDSAELFRKQLHKLRYP 1025
Cdd:pfam02893   67 LKGGANLFPNGIQVETGSND--KFSFAGFVTRDEAIEFILALLKNAHP 112
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
 1797-1898 1.61e-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: 68.12  E-value: 1.61e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1797 SYEGILYKKGAFMKPWKARWFVLdkTKHQLRYYDHRMDTECKGVIDLAEVEAVapgtptigAPKTVDEKAF-FDVKTTRR 1875
Cdd:cd10573     4 SKEGYLTKLGGIVKNWKTRWFVL--RRNELKYFKTRGDTKPIRVLDLRECSSV--------QRDYSQGKVNcFCLVFPER 73

                          90       100
                  ....*....|....*....|...
gi 568993627 1876 VYNFCAQDVPSAQQWVDRIQSCL 1898
Cdd:cd10573    74 TFYMYANTEEEADEWVKLLKWKL 96
PH_SWAP-70 cd13273
Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called ...
 1799-1898 4.22e-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: 64.62  E-value: 4.22e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1799 EGILYKKGAFMKPWKARWFVLdkTKHQLRYYDHRMDTECKGVIDLAE---VEavapgtptiGAPKTVDEKAFFDVKTTRR 1875
Cdd:cd13273    11 KGYLWKKGHLLPTWTERWFVL--KPNSLSYYKSEDLKEKKGEIALDSnccVE---------SLPDREGKKCRFLVKTPDK 79

                          90       100
                  ....*....|....*....|...
gi 568993627 1876 VYNFCAQDVPSAQQWVDRIQSCL 1898
Cdd:cd13273    80 TYELSASDHKTRQEWIAAIQTAI 102
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 1798-1894 8.07e-12

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: 62.95  E-value: 8.07e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1798 YEGILYKKGAF-MKPWKARWFVLDktKHQLRYYDHRMD--TECKGVIDLAEVEAVAPGTPTigapktvDEKAFFDVKTT- 1873
Cdd:cd00821     1 KEGYLLKRGGGgLKSWKKRWFVLF--EGVLLYYKSKKDssYKPKGSIPLSGILEVEEVSPK-------ERPHCFELVTPd 71

                          90       100
                  ....*....|....*....|.
gi 568993627 1874 RRVYNFCAQDVPSAQQWVDRI 1894
Cdd:cd00821    72 GRTYYLQADSEEERQEWLKAL 92
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
 1800-1894 1.71e-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: 1.71e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1800 GILYKKGAFMKPWKARWFVLdkTKHQLRYYDHRMDTECKGVIDLAEVEAVAPgtptIGAPKTvdeKAFFDVKTTRRVYNF 1879
Cdd:cd13298    10 GYLLKRSRKTKNWKKRWVVL--RPCQLSYYKDEKEYKLRRVINLSELLAVAP----LKDKKR---KNVFGIYTPSKNLHF 80

                          90
                  ....*....|....*
gi 568993627 1880 CAQDVPSAQQWVDRI 1894
Cdd:cd13298    81 RATSEKDANEWVEAL 95
PH_TBC1D2A cd01265
TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1 ...
 1798-1896 8.11e-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: 60.41  E-value: 8.11e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1798 YEGILYKKGAFMKPWKARWFVLDKTKHQLRYYDHRMDTECKGVIDLAeveavapgtptiGAPKTVD---EKAFFDVKTTR 1874
Cdd:cd01265     5 YLNKLETRGLGLKGWKRRWFVLDESKCQLYYYRSPQDATPLGSIDLS------------GAAFSYDpeaEPGQFEIHTPG 72

                          90       100
                  ....*....|....*....|..
gi 568993627 1875 RVYNFCAQDVPSAQQWVDRIQS 1896
Cdd:cd01265    73 RVHILKASTRQAMLYWLQALQS 94
PH_PHLDB1_2 cd14673
Pleckstrin homology-like domain-containing family B member 2 pleckstrin homology (PH) domain; ...
 1796-1894 1.25e-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: 60.28  E-value: 1.25e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1796 RSYEGILYKKGAFMKPWKARWFVLDKTKHQLRYYDHRMDTECKGVIDLAEVEAVAPGTPTiGAPKTVDEKAFFDVKTTRR 1875
Cdd:cd14673     3 KRCRGFLTKMGGKIKTWKKRWFVFDRNKRTLSYYVDKHEKKLKGVIYFQAIEEVYYDHLR-SAAKSPNPALTFCVKTHDR 81

                          90
                  ....*....|....*....
gi 568993627 1876 VYNFCAQDVPSAQQWVDRI 1894
Cdd:cd14673    82 LYYMVAPSPEAMRIWMDVI 100
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 1798-1899 1.50e-10

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 59.88  E-value: 1.50e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627  1798 YEGILYKKG-AFMKPWKARWFVLdkTKHQLRYYDHRM---DTECKGVIDLAEVEAVapgtpTIGAPKTVDEKAFFDVKTT 1873
Cdd:pfam00169    3 KEGWLLKKGgGKKKSWKKRYFVL--FDGSLLYYKDDKsgkSKEPKGSISLSGCEVV-----EVVASDSPKRKFCFELRTG 75

                           90       100       110
                   ....*....|....*....|....*....|
gi 568993627  1874 ----RRVYNFCAQDVPSAQQWVDRIQSCLS 1899
Cdd:pfam00169   76 ertgKRTYLLQAESEEERKDWIKAIQSAIR 105
PH_GRP1-like cd01252
General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 ...
 1795-1899 2.86e-10

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: 59.64  E-value: 2.86e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1795 NRSYEGILYKKGAFMKPWKARWFVLdkTKHQLRYYDHRMDTECKGVIDLAEV--------------EAVAPGTP-TIGAP 1859
Cdd:cd01252     2 NPDREGWLLKLGGRVKSWKRRWFIL--TDNCLYYFEYTTDKEPRGIIPLENLsvrevedkkkpfcfELYSPSNGqVIKAC 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 568993627 1860 KT-VDEKAffdVKTTRRVYNFCAQDVPSAQQWVDRIQSCLS 1899
Cdd:cd01252    80 KTdSDGKV---VEGNHTVYRISAASEEERDEWIKSIKASIS 117
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
 1799-1900 3.86e-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: 58.17  E-value: 3.86e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1799 EGILYKKG--AFMKPWKARWFVLDKTkhQLRYYDHRMDTECKGVIDLAEVEAVAPgtptIGapktvDEKafFDVKTTRRV 1876
Cdd:cd13253     3 SGYLDKQGgqGNNKGFQKRWVVFDGL--SLRYFDSEKDAYSKRIIPLSAISTVRA----VG-----DNK--FELVTTNRT 69

                          90       100
                  ....*....|....*....|....
gi 568993627 1877 YNFCAQDVPSAQQWVDRIQSCLSD 1900
Cdd:cd13253    70 FVFRAESDDERNLWCSTLQAAISE 93
PH-GRAM cd10570
Pleckstrin Homology-Glucosyltransferases, Rab-like GTPase activators and Myotubularins ...
 928-1019 6.43e-10

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: 57.78  E-value: 6.43e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627  928 PALLPAEGAVFLTTYRVIFTGMPTDplvgeQVVVRSFPVAALTKEKRISVQtpvdQLLQDGLQLRSCTFQLLKMAFDEEv 1007
Cdd:cd10570    14 PRKLPLEGTLYLSTYRLIFSSKADG-----DETKLVIPLVDITDVEKIAGA----SFLPSGLIITCKDFRTIKFSFDSE- 83

                          90
                  ....*....|..
gi 568993627 1008 gSDSAELFRKQL 1019
Cdd:cd10570    84 -DEAVKVIARVL 94
PH_Gab2_2 cd13384
Grb2-associated binding protein family pleckstrin homology (PH) domain; The Gab subfamily ...
 1798-1894 4.06e-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: 56.30  E-value: 4.06e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1798 YEGILYK----KGAFMKPWKARWFVLDKT----KHQLRYYDHRMDTECKGVIDLAEVEAVAPGTpTIGAPKTVDEKAFFD 1869
Cdd:cd13384     5 YEGWLTKsppeKRIWRAKWRRRYFVLRQSeipgQYFLEYYTDRTCRKLKGSIDLDQCEQVDAGL-TFETKNKLKDQHIFD 83

                          90       100
                  ....*....|....*....|....*
gi 568993627 1870 VKTTRRVYNFCAQDVPSAQQWVDRI 1894
Cdd:cd13384    84 IRTPKRTYYLVADTEDEMNKWVNCI 108
PH2_MyoX cd13296
Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular ...
 1800-1899 5.96e-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: 55.17  E-value: 5.96e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1800 GILYKKGAFM-----KPWKARWFVLDKTKhqLRYYDHRMDTE-CKGVIDLAEVEAVAPGTPTIGApktvdekafFDVKTT 1873
Cdd:cd13296     3 GWLTKKGGGSstlsrRNWKSRWFVLRDTV--LKYYENDQEGEkLLGTIDIRSAKEIVDNDPKENR---------LSITTE 71

                          90       100
                  ....*....|....*....|....*.
gi 568993627 1874 RRVYNFCAQDVPSAQQWVDRIQSCLS 1899
Cdd:cd13296    72 ERTYHLVAESPEDASQWVNVLTRVIS 97
PH_ORP10_ORP11 cd13291
Human Oxysterol binding protein (OSBP) related proteins 10 and 11 (ORP10 and ORP11) Pleckstrin ...
 1798-1897 8.46e-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: 54.99  E-value: 8.46e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1798 YEGILYKKGAFMKPWKARWFVLDKTKHQLRYY--DHRMDTECKGVIDLAevEAVApgtptigAPKTVDEKAFFDVKTTRR 1875
Cdd:cd13291     1 LEGQLLKYTNVVKGWQNRWFVLDPDTGILEYFlsEESKNQKPRGSLSLA--GAVI-------SPSDEDSHTFTVNAANGE 71

                          90       100
                  ....*....|....*....|..
gi 568993627 1876 VYNFCAQDVPSAQQWVDRIQSC 1897
Cdd:cd13291    72 MYKLRAADAKERQEWVNRLRAV 93
PH_Gab-like cd13324
Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are ...
 1798-1894 1.44e-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: 1.44e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1798 YEGILYK----KGAFMKPWKARWFVLDKTK-----HQLRYYDHRMDTECKGVIDLAEVEAVAPGTPTigAPKTVDEKAFF 1868
Cdd:cd13324     3 YEGWLTKsppeKKIWRAAWRRRWFVLRSGRlsggqDVLEYYTDDHCKKLKGIIDLDQCEQVDAGLTF--EKKKFKNQFIF 80

                          90       100
                  ....*....|....*....|....*.
gi 568993627 1869 DVKTTRRVYNFCAQDVPSAQQWVDRI 1894
Cdd:cd13324    81 DIRTPKRTYYLVAETEEEMNKWVRCI 106
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
 1799-1899 1.96e-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: 53.46  E-value: 1.96e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1799 EGILYKKGAFMKPWKARWFVLDKTkhQLRYYDHRMDTECK--GVIDLAEVEAVAPGtptigapktvDEKAFFDVKTTRRV 1876
Cdd:cd13282     2 AGYLTKLGGKVKTWKRRWFVLKNG--ELFYYKSPNDVIRKpqGQIALDGSCEIARA----------EGAQTFEIVTEKRT 69

                          90       100
                  ....*....|....*....|...
gi 568993627 1877 YNFCAQDVPSAQQWVDRIQSCLS 1899
Cdd:cd13282    70 YYLTADSENDLDEWIRVIQNVLR 92
PH_RASA1 cd13260
RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 ...
 1800-1897 7.84e-08

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: 51.96  E-value: 7.84e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1800 GILYKKGAFMKPWKARWFVLDKTKHQLRYYDHRMDTECKGVIDLAE--VEAVAPGtpTIGAPK--TVDEKAFFDVkttrR 1875
Cdd:cd13260     7 GYLLKKGGKNKKWKNLYFVLEGKEQHLYFFDNEKRTKPKGLIDLSYcsLYPVHDS--LFGRPNcfQIVVRALNES----T 80

                          90       100
                  ....*....|....*....|..
gi 568993627 1876 VYNFCAQDVPSAQQWVDRIQSC 1897
Cdd:cd13260    81 ITYLCADTAELAQEWMRALRAF 102
PH2_ADAP cd01251
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called ...
 1799-1899 8.74e-08

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: 51.82  E-value: 8.74e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1799 EGILYKKGAFMK-PWKARWFVLDKTKhqLRYYDHRMDTECKGVIDLAEVE---AVAPGTPTiGAPKTVDEKafFDVKTTR 1874
Cdd:cd01251     5 EGYLEKTGPKQTdGFRKRWFTLDDRR--LMYFKDPLDAFPKGEIFIGSKEegySVREGLPP-GIKGHWGFG--FTLVTPD 79

                          90       100
                  ....*....|....*....|....*
gi 568993627 1875 RVYNFCAQDVPSAQQWVDRIQSCLS 1899
Cdd:cd01251    80 RTFLLSAETEEERREWITAIQKVLE 104
PH_Btk cd01238
Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of ...
 1799-1853 7.51e-07

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: 50.30  E-value: 7.51e-07
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 568993627 1799 EGILYKKG---AFMKP--WKARWFVLdkTKHQLRYYDHRMDT--ECKGVIDLAE---VEAVAPGT 1853
Cdd:cd01238     2 EGLLVKRSqgkKRFGPvnYKERWFVL--TKSSLSYYEGDGEKrgKEKGSIDLSKvrcVEEVKDEA 64
PH1_Pleckstrin_2 cd13301
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in ...
 1799-1843 8.65e-07

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: 49.29  E-value: 8.65e-07
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*
gi 568993627 1799 EGILYKKGAFMKPWKARWFVLdkTKHQLRYYDHRMDTECKGVIDL 1843
Cdd:cd13301     6 EGYLVKKGHVVNNWKARWFVL--KEDGLEYYKKKTDSSPKGMIPL 48
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
 1792-1894 2.06e-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: 48.18  E-value: 2.06e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1792 ESENRSYEGILYKKGAFMKPWKARWFVLDKTKhqLRYYDHRMDTECKGVIDLAEVEAVAPgtptigapktVDEKAF---F 1868
Cdd:cd13255     2 ISEAVLKAGYLEKKGERRKTWKKRWFVLRPTK--LAYYKNDKEYRLLRLIDLTDIHTCTE----------VQLKKHdntF 69

                          90       100
                  ....*....|....*....|....*.
gi 568993627 1869 DVKTTRRVYNFCAQDVPSAQQWVDRI 1894
Cdd:cd13255    70 GIVTPARTFYVQADSKAEMESWISAI 95
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
 1799-1898 2.54e-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: 47.70  E-value: 2.54e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1799 EGILYKKGAFMKPWKARWFVLDKTK-HQLRYYDHRMDTECKGVIDLAEVEAVApgtptiGAPKTVDEKAFFDVKTTRRVY 1877
Cdd:cd13276     2 AGWLEKQGEFIKTWRRRWFVLKQGKlFWFKEPDVTPYSKPRGVIDLSKCLTVK------SAEDATNKENAFELSTPEETF 75

                          90       100
                  ....*....|....*....|.
gi 568993627 1878 NFCAQDVPSAQQWVDRIQSCL 1898
Cdd:cd13276    76 YFIADNEKEKEEWIGAIGRAI 96
PH2_TAPP1_2 cd13271
Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal ...
 1800-1849 2.65e-06

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: 48.12  E-value: 2.65e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 568993627 1800 GILYKKGAFMKPWKARWFVLDktKHQLRYYDHRMDTECKGVIDLAEVEAV 1849
Cdd:cd13271    12 GYCVKQGAVRKNWKRRFFILD--DNTISYYKSETDKEPLRTIPLREVLKV 59
GRAM smart00568
domain in glucosyltransferases, myotubularins and other putative membrane-associated proteins;
898-976 7.83e-06

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


Pssm-ID: 214725 [Multi-domain]  Cd Length: 60  Bit Score: 44.89  E-value: 7.83e-06
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 568993627    898 LPGEECVLDGLRVYLLpdgreegvggsgggpALLPAEGAVFLTTYRVIFTGMPTDPLvgeqvVVRSFPVAALTKEKRIS 976
Cdd:smart00568    2 LPEEEKLIADYSCYLS---------------RTGPVQGRLYISNYRLCFRSNLPGKL-----TKVVIPLADITRIEKST 60
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
 1799-1895 1.03e-05

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: 46.46  E-value: 1.03e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1799 EGILYKKGAFMKPWKARWFVLdktKHQ-LRYYdhRMDTEC---KGVIDLAEVEAVAPGTPTIGAPKTvdekafFDVKTTR 1874
Cdd:cd13215    24 SGYLSKRSKRTLRYTRYWFVL---KGDtLSWY--NSSTDLyfpAGTIDLRYATSIELSKSNGEATTS------FKIVTNS 92

                          90       100
                  ....*....|....*....|.
gi 568993627 1875 RVYNFCAQDVPSAQQWVDRIQ 1895
Cdd:cd13215    93 RTYKFKADSETSADEWVKALK 113
dDENN pfam03455
dDENN domain; This region is always found associated with pfam02141. It is predicted to form a ...
 407-453 1.37e-05

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: 44.11  E-value: 1.37e-05
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 568993627   407 FHKAAFLGQRGLVEDDFLMKVLEGMAFAGFVSERG-VPYRATDLFDEL 453
Cdd:pfam03455    1 FDKEAFLKSLPSDSRPFLSQFLETQMFNEFIEERLeSSDPSIDLFDEE 48
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
 1800-1892 4.72e-05

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: 44.19  E-value: 4.72e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1800 GILYKK-GAFMKPWKARWFVLdkTKHQLRYYDHRMDTECKGVIDLaeveavaPG---TPTIGAPKTVDEKAFFDVKTTRR 1875
Cdd:cd13248    11 GWLHKQgGSGLKNWRKRWFVL--KDNCLYYYKDPEEEKALGSILL-------PSytiSPAPPSDEISRKFAFKAEHANMR 81

                          90
                  ....*....|....*..
gi 568993627 1876 VYNFCAQDVPSAQQWVD 1892
Cdd:cd13248    82 TYYFAADTAEEMEQWMN 98
PH1_ADAP cd13252
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 1; ADAP (also called ...
 1797-1859 5.05e-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: 44.17  E-value: 5.05e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 568993627 1797 SYEGILYKKGAFMKPWKARWFVLDKTKHQLRYYDHRMDTECKGVIDLAEVEAV-APGtpTIGAP 1859
Cdd:cd13252     2 SKEGFLWKRGKDNNQFKQRKFVLSEREGTLKYFVKEDAKEPKAVISIEELNATfQPE--KIGHP 63
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
 1799-1891 7.30e-05

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: 44.15  E-value: 7.30e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1799 EGILYKKGAFMKPWKARWFVLdkTKHQLRYYDHRMDTECKGVIDLAEVeavapgtpTIGAPKTVDEKAF---FDVKTTrR 1875
Cdd:cd13288    11 EGYLWKKGERNTSYQKRWFVL--KGNLLFYFEKKGDREPLGVIVLEGC--------TVELAEDAEPYAFairFDGPGA-R 79

                          90
                  ....*....|....*.
gi 568993627 1876 VYNFCAQDVPSAQQWV 1891
Cdd:cd13288    80 SYVLAAENQEDMESWM 95
SPA pfam08616
Stabilization of polarity axis; Swiss:Q99222 has been shown to interact with the outer plaque ...
 230-322 2.03e-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: 42.66  E-value: 2.03e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627   230 NVLSLFCAALTEHKVLFLsrSYQRLADA-CRGLLALL------FPLRY----SFTYVPIlpAQLLEVLSTPtPFIIGV-N 297
Cdd:pfam08616   14 PIILLINALLTSKRIIFL--SYQRSAGEvSEFVLALCnlisggFVLRGftnnSFPYVDL--SKLDALRKVP-GYIAGVtN 88

                           90       100
                   ....*....|....*....|....*
gi 568993627   298 AAFqAETQELLDVIVaDLDGGTVTV 322
Cdd:pfam08616   89 PIF-ENQDQWWDVLC-DLDSGSVKL 111
PH_FAPP1_FAPP2 cd01247
Four phosphate adaptor protein 1 and 2 Pleckstrin homology (PH) domain; Human FAPP1 (also ...
 1799-1850 2.09e-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: 2.09e-04
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....
gi 568993627 1799 EGILYKKGAFMKPWKARWFVLDKTkhQLRYYDHRMDTE--CKGVIDLAEVEAVA 1850
Cdd:cd01247     2 EGVLWKWTNYLSGWQPRWFVLDDG--VLSYYKSQEEVNqgCKGSVKMSVCEIIV 53
PH_GPBP cd13283
Goodpasture antigen binding protein Pleckstrin homology (PH) domain; The GPBP (also called ...
 1799-1896 2.36e-04

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: 41.89  E-value: 2.36e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1799 EGILYKKGAFMKPWKARWFVL-DKTkhqLRYYDHRMDTE--CKGVIDLAEVeavapgtptIGAPKTVDEKAFfDVKTTRR 1875
Cdd:cd13283     2 RGVLSKWTNYIHGWQDRYFVLkDGT---LSYYKSESEKEygCRGSISLSKA---------VIKPHEFDECRF-DVSVNDS 68

                          90       100
                  ....*....|....*....|.
gi 568993627 1876 VYNFCAQDVPSAQQWVDRIQS 1896
Cdd:cd13283    69 VWYLRAESPEERQRWIDALES 89
PH_ORP9 cd13290
Human Oxysterol binding protein related protein 9 Pleckstrin homology (PH) domain; Human ORP9 ...
 1799-1895 2.64e-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: 42.05  E-value: 2.64e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1799 EGILYKKGAFMKPWKARWFVLDKTKHQLRYY---DHRMDTECKGVIDLAeveavapgtptiGAPKTVD--EKAFFDVKTT 1873
Cdd:cd13290     2 EGPLSKWTNVMKGWQYRWFVLDDNAGLLSYYtskEKMMRGSRRGCVRLK------------GAVVGIDdeDDSTFTITVD 69

                          90       100
                  ....*....|....*....|..
gi 568993627 1874 RRVYNFCAQDVPSAQQWVDRIQ 1895
Cdd:cd13290    70 QKTFHFQARDAEERERWIRALE 91
PH_Osh1p_Osh2p_yeast cd13292
Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p ...
 1796-1844 1.29e-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: 39.98  E-value: 1.29e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568993627 1796 RSYEGILYKKGAFMKPWKARWFVLDKTkhQLRYYDHRMD--TECKGVIDLA 1844
Cdd:cd13292     2 PTMKGYLKKWTNYAKGYKTRWFVLEDG--VLSYYRHQDDegSACRGSINMK 50
Niban-like cd23949
Niban-like protein; Niban-like proteins contain an N-terminal Pleckstrin-Homology (PH) domain ...
 1792-1898 1.44e-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: 1.44e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1792 ESENRSYEGILYKKGAFMKPWKARWFVLdKTKHQLRYYDHRMDTE----CKGVIDLAEVEAVAPGT----------PTIG 1857
Cdd:cd23949    58 EDRKVIFSGKLSKYGEDSKKWKERFCVV-RGDYNLEYYESKEAYErgkkPKGSINLAGYKVLTSPEeylelvdrkfPDLA 136

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 568993627 1858 APKTVDEKAFFDVKTT---------RRVYNFCAQDVPSAQQWVDRIQSCL 1898
Cdd:cd23949   137 GKSEKASVPFPERPPPftlelyhpyRRHYYFCFETEKEQEEWVAVLQDCI 186
PH_Gab3 cd13385
Grb2-associated binding protein 3 pleckstrin homology (PH) domain; The Gab subfamily includes ...
 1812-1897 1.77e-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: 40.34  E-value: 1.77e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1812 WKARWFVLDKTKHQ-----LRYYDHRMDTECKGVIDLAEVEAVAPGTPTIgAPKTVDEKAFFDVKTTRRVYNFCAQDVPS 1886
Cdd:cd13385    26 WRKRWFVLRRGRMSgnpdvLEYYRNNHSKKPIRVIDLSECEVLKHSGPNF-IRKEFQNNFVFIVKTTYRTFYLVAKTEEE 104

                          90
                  ....*....|..
gi 568993627 1887 AQQWVDRI-QSC 1897
Cdd:cd13385   105 MQVWVHNIsQIC 116
PH_Boi cd13316
Boi family Pleckstrin homology domain; Yeast Boi proteins Boi1 and Boi2 are functionally ...
 1798-1843 1.97e-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: 1.97e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*.
gi 568993627 1798 YEGILYKKGAFMKPWKARWFVLDKTkhQLRYYDHRMDTECKGVIDL 1843
Cdd:cd13316     2 HSGWMKKRGERYGTWKTRYFVLKGT--RLYYLKSENDDKEKGLIDL 45
PH_GAP1-like cd01244
RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; ...
 1799-1892 2.32e-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: 39.58  E-value: 2.32e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1799 EGILYK------KGAFMKPWKARWFVLdkTKHQLRYYDHRMDTECKgVIDLAEVEAVapgtptigapKTVDEKAF----- 1867
Cdd:cd01244     2 EGYLIKraqgrkKKFGRKNFKKRYFRL--TNEALSYSKSKGKQPLC-SIPLEDILAV----------ERVEEESFkmknm 68

                          90       100
                  ....*....|....*....|....*
gi 568993627 1868 FDVKTTRRVYNFCAQDVPSAQQWVD 1892
Cdd:cd01244    69 FQIVQPDRTLYLQAKNVVELNEWLS 93
PH_11 pfam15413
Pleckstrin homology domain; This Pleckstrin homology domain is found in some fungal species.
 1799-1895 2.39e-03

Pleckstrin homology domain; This Pleckstrin homology domain is found in some fungal species.


Pssm-ID: 405988  Cd Length: 105  Bit Score: 39.49  E-value: 2.39e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627  1799 EGILYKKGAfmKPWKARWFVldKTKH-QLRYYDHRMDTECKGVIDLAEVE-------AVAPGTPTIG--APKTVDEKaFF 1868
Cdd:pfam15413    2 EGYLKKKGP--KTWKHRWFA--VLRNgVLFYYKSEKMKVVKHVIVLSNYIvgklgtdIISGALFKIDniRSETSDDL-LL 76

                           90       100
                   ....*....|....*....|....*..
gi 568993627  1869 DVKTTRRVYNFCAQDVPSAQQWVDRIQ 1895
Cdd:pfam15413   77 EISTETKIFFLYGDNNEETYEWVEALQ 103
PH_CNK_mammalian-like cd01260
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
 1799-1845 2.51e-03

Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; CNK family members function as protein scaffolds, regulating the activity and the subcellular localization of RAS activated RAF. There is a single CNK protein present in Drosophila and Caenorhabditis elegans in contrast to mammals which have 3 CNK proteins (CNK1, CNK2, and CNK3). All of the CNK members contain a sterile a motif (SAM), a conserved region in CNK (CRIC) domain, and a PSD-95/DLG-1/ZO-1 (PDZ) domain, and, with the exception of CNK3, a PH domain. A CNK2 splice variant CNK2A also has a PDZ domain-binding motif at its C terminus and Drosophila CNK (D-CNK) also has a domain known as the Raf-interacting region (RIR) that mediates binding of the Drosophila Raf kinase. This cd contains CNKs from mammals, chickens, amphibians, fish, and crustacea. 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: 269962  Cd Length: 114  Bit Score: 39.70  E-value: 2.51e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|.
gi 568993627 1799 EGILYKK----GAFMKPWKARWFVLDktKHQLRYYDHRMDTECKGVIDLAE 1845
Cdd:cd01260    16 QGWLWKKkeakSFFGQKWKKYWFVLK--GSSLYWYSNQQDEKAEGFINLPD 64
PH_evt cd13265
Evectin Pleckstrin homology (PH) domain; There are 2 members of the evectin family (also ...
 1800-1891 2.54e-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: 39.21  E-value: 2.54e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1800 GILYKKGAFMKPWKARWFVLdKTKHQLRYYDHRMDTECKGVIDL-AEVEAVAPGT--PTIGAPKTVDEKAFFDVKT-TRR 1875
Cdd:cd13265     7 GWLLRQSTILKRWKKNWFVL-YGDGNLVYYEDETRREVEGRINMpRECRNIRVGLecRDVQPPEGRSRDCLLQIVLrDGS 85

                          90
                  ....*....|....*.
gi 568993627 1876 VYNFCAQDVPSAQQWV 1891
Cdd:cd13265    86 TLFLCAESADDALAWK 101
PH_Gab1_Gab2 cd01266
Grb2-associated binding proteins 1 and 2 pleckstrin homology (PH) domain; The Gab subfamily ...
 1812-1894 4.02e-03

Grb2-associated binding proteins 1 and 2 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 and Gab2 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: 241297  Cd Length: 123  Bit Score: 39.16  E-value: 4.02e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1812 WKARWFVLDKTKHQ-----LRYYDHRMDTECKGVIDLAEVEAVAPGTptIGAPKTVDEKAFFDVKTTRRVYNFCAQDVPS 1886
Cdd:cd01266    24 WKKRWFVLRSGRLSgdpdvLEYYKNDHAKKPIRVIDLNLCEQVDAGL--TFNKKELENSYIFDIKTIDRIFYLVAETEED 101


                  ....*...
gi 568993627 1887 AQQWVDRI 1894
Cdd:cd01266   102 MNKWVRNI 109
PH_M-RIP cd13275
Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed ...
 1800-1851 5.00e-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: 38.47  E-value: 5.00e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 568993627 1800 GILYKKGAFMKPWKARWFVLdkTKHQLRYY-DHRMD--TECKGVIDLAEVEAVAP 1851
Cdd:cd13275     3 GWLMKQGSRQGEWSKHWFVL--RGAALKYYrDPSAEeaGELDGVIDLSSCTEVTE 55
PH2_PH_fungal cd13299
Fungal proteins Pleckstrin homology (PH) domain, repeat 2; The functions of these fungal ...
 1798-1898 8.06e-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: 37.61  E-value: 8.06e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 568993627 1798 YEGILYK-KGAFMKPWKARWFVLdkTKHQLRYYDHRMDTECKGVIDLAEVEAVAPGTPTigapkTVDEKAFFDVKTTRRV 1876
Cdd:cd13299     8 EQGYLQVlKKKGVNQWKKYWLVL--RNRSLSFYKDQSEYSPVKIIPIDDIIDVVELDPL-----SKSKKWCLQIITPEKR 80

                          90       100
                  ....*....|....*....|..
gi 568993627 1877 YNFCAQDVPSAQQWVDRIQSCL 1898
Cdd:cd13299    81 IRFCADDEESLIKWLGALKSLL 102
PH_OSBP_ORP4 cd13284
Human Oxysterol binding protein and OSBP-related protein 4 Pleckstrin homology (PH) domain; ...
 1798-1844 9.10e-03

Human Oxysterol binding protein and OSBP-related protein 4 Pleckstrin homology (PH) domain; Human OSBP is proposed to function is sterol-dependent regulation of ERK dephosphorylation and sphingomyelin synthesis as well as modulation of insulin signaling and hepatic lipogenesis. It contains a N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. OSBPs and Osh1p PH domains specifically localize to the Golgi apparatus in a PtdIns4P-dependent manner. ORP4 is proposed to function in Vimentin-dependent sterol transport and/or signaling. Human ORP4 has 2 forms, a long (ORP4L) and a short (ORP4S). ORP4L contains a N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. ORP4S is truncated and contains only an OSBP-related domain. Oxysterol binding proteins are a multigene family that is conserved in yeast, flies, worms, mammals and plants. 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: 270101  Cd Length: 99  Bit Score: 37.36  E-value: 9.10e-03
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 568993627 1798 YEGILYKKGAFMKPWKARWFVLDKTkhQLRYYDHR--MDTECKGVIDLA 1844
Cdd:cd13284     1 MKGWLLKWTNYIKGYQRRWFVLSNG--LLSYYRNQaeMAHTCRGTINLA 47
 
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH