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Conserved domains on  [gi|1034611600|ref|XP_016858840|]
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pleckstrin homology domain-containing family H member 2 isoform X1 [Homo sapiens]

Protein Classification

FERM_F1_PLEKHH2 and FERM_C-lobe_PLEKHH1_PLEKHH2 domain-containing protein( domain architecture ID 12988233)

protein containing domains PH1_PLEKHH1_PLEKHH2, MyTH4, FERM_F1_PLEKHH2, and FERM_C-lobe_PLEKHH1_PLEKHH2

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
FERM_F1_PLEKHH2 cd17179
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in pleckstrin ...
 1079-1181 6.49e-73

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in pleckstrin homology domain-containing family H member 2 (PLEKHH2); PLEKHH2 is a novel podocyte protein downregulated in human focal segmental glomerulosclerosis. It is highly enriched in renal glomerular podocytes, and acts as a novel, important component of the podocyte foot processes. PLEKHH2 contains a putative alpha-helical coiled-coil segment within the N-terminal half, and two Pleckstrin homology (PH) domains, a MyTH4 domain, and a FERM (Band 4.1, ezrin, radixin, moesin) domain within the C-terminal half. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). PLEKHH2 is involved in matrix adhesion and actin dynamics. It directly interacts through its FERM domain with the focal adhesion protein Hic-5 and actin.


:

Pssm-ID: 340699  Cd Length: 103  Bit Score: 237.56  E-value: 6.49e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600 1079 PFSIPVHFMNGIYQVVGFDASTTVEEFLNTLNQDTGMRKPAQSGFALFTDDPSGRDLEHCLQGNIKICDIISKWEQASKE 1158
Cdd:cd17179      1 PFSIPVHFMNGTYQVVGFDASTTVEEFLNTLNQDTGMRKPGQSGFALFTDDPSGKDLEHCLQGNIKICDIISKWEQASKE 80

                           90       100
                   ....*....|....*....|...
gi 1034611600 1159 QQPGKCEGTRTVRLTYKNRLYFS 1181
Cdd:cd17179     81 QHPGKCEGTRTVRLTYKNRLYFS 103
FERM_C-lobe_PLEKHH1_PLEKHH2 cd13206
FERM domain C-lobe of Pleckstrin homology domain-containing family H; PLEKHH1 and PLEKHH2 ...
 1309-1408 6.13e-62

FERM domain C-lobe of Pleckstrin homology domain-containing family H; 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 composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


:

Pssm-ID: 241360  Cd Length: 100  Bit Score: 206.13  E-value: 6.13e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600 1309 GAKLFLAKPITPSSLGSTFLWLAVHEDGLSLLEYNSMRLIVSYVYKSLMTFGGYQDDFMVVINNTHSKDKPTEKLLFAMA 1388
Cdd:cd13206      1 GAKLFAAKPKTPSSLENTVVWLAVNEDGISILDYNTMRLVVTYPYSSVMTFGGCQDDFMLVVNSIKDKKKPTEKLLFAMA 80

                           90       100
                   ....*....|....*....|
gi 1034611600 1389 KPKILEITLLIASYINNFHQ 1408
Cdd:cd13206     81 KPKILEITLLIASYINAFHQ 100
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
 665-760 1.42e-51

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: 176.33  E-value: 1.42e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELSASCSILRGDNKQTVQLTTEKHTYYLTADSPNIL 744
Cdd:cd13282      1 KAGYLTKLGGKVKTWKRRWFVLKNGELFYYKSPNDVIRKPQGQIALDGSCEIARAEGAQTFEIVTEKRTYYLTADSENDL 80

                           90
                   ....*....|....*.
gi 1034611600  745 EEWIKVLQNVLRVQAA 760
Cdd:cd13282     81 DEWIRVIQNVLRRQAS 96
MyTH4 smart00139
Domain in Myosin and Kinesin Tails; Domain present twice in myosin-VIIa, and also present in 3 ...
 914-1069 4.83e-45

Domain in Myosin and Kinesin Tails; Domain present twice in myosin-VIIa, and also present in 3 other myosins.


:

Pssm-ID: 214535  Cd Length: 152  Bit Score: 159.83  E-value: 4.83e-45
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600   914 HSKEGIISPLTTLPSEALQTEAIKLFKTCQLFINAaVDSPAIDYHISLAQSALQICLTHPELQNEICCQLIKQTRRRqpQ 993
Cdd:smart00139    1 YTKDPIKTSLLKLESDELQKEAVKIFKAILKFMGD-IPLPRPDSHLDLVQFILQKGLDHPELRDEIYCQLIKQLTDN--P 77

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034611600   994 NQPGPLQGWQLLALCVGLFLPHHPFLWLLRLHLKRNADSRTeFGKYAIYCQRCVERTQQNGDREARPSRMEILSTL 1069
Cdd:smart00139   78 SRQSEERGWQLLYLCTSLFPPSERLLPYLLQFLSRRADPGS-EQGLAKYCLYRLERTLKNGARKQPPSRLELEAIL 152
B41 smart00295
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ...
 1082-1313 1.28e-29

Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in myosins, ezrin, radixin, moesin, protein tyrosine phosphatases. Plasma membrane-binding domain. These proteins play structural and regulatory roles in the assembly and stabilization of specialized plasmamembrane domains. Some PDZ domain containing proteins bind one or more of this family. Now includes JAKs.


:

Pssm-ID: 214604 [Multi-domain]  Cd Length: 201  Bit Score: 117.40  E-value: 1.28e-29
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  1082 IPVHFMNGIYQVVGFDASTTVEEFLNTLNQDTGMRkpAQSGFALFTDDPSGrDLEHCLQGNIKICDIISKWEqaskeqqp 1161
Cdd:smart00295    2 LKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIR--ESEYFGLQFEDPDE-DLRHWLDPAKTLLDQDVKSE-------- 70

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  1162 gkcegtrTVRLTYKNRLYFSVQARGETDREKLLLMY-QTNDQIINGLFPLNKDLALEMAALLSQVEIGDFERPFSTPAGH 1240
Cdd:smart00295   71 -------PLTLYFRVKFYPPDPNQLKEDPTRLNLLYlQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHDLRGE 143

                           170       180       190       200       210       220       230
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034611600  1241 VtnqckvnqtlkqVIEKFYPKRYRDGCSEEQLRqlcQRLSTRWMALRGHSAADCVRIYLTVARKWPFFGAKLF 1313
Cdd:smart00295  144 L------------SLKRFLPKQLLDSRKLKEWR---ERIVELHKELIGLSPEEAKLKYLELARKLPTYGVELF 201
PRK12704 super family cl36166
phosphodiesterase; Provisional
 1-92 6.01e-06

phosphodiesterase; Provisional


The actual alignment was detected with superfamily member PRK12704:

Pssm-ID: 237177 [Multi-domain]  Cd Length: 520  Bit Score: 50.55  E-value: 6.01e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    1 MQQLERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESETRLYNKCQDLESLIQEKDDVIQNL-ELQLEEQKQIRIQ-- 77
Cdd:PRK12704    84 LQKLEKRLLQKEENLDRKLELLEKREEELEKKEKELEQKQQELEKKEEELEELIEEQLQELERIsGLTAEEAKEILLEkv 163

                           90
                   ....*....|....*
gi 1034611600   78 EAKIIEEKAAKIKEW 92
Cdd:PRK12704   164 EEEARHEAAVLIKEI 178
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 771-873 2.29e-05

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: 44.85  E-value: 2.29e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600   771 PTMKGLLTKVKHGYS---KRVWCTLIGKTLYYFRS---QEDKFPLGQIKLWEAKVEEVDRSCDSDEDyeasgrsllsthY 844
Cdd:smart00233    1 VIKEGWLYKKSGGGKkswKKRYFVLFNSTLLYYKSkkdKKSYKPKGSIDLSGCTVREAPDPDSSKKP------------H 68

                            90       100
                    ....*....|....*....|....*....
gi 1034611600   845 TIVIHPKDQGPTYLLIGSKHEKDTWLYHL 873
Cdd:smart00233   69 CFEIKTSDRKTLLLQAESEEEREKWVEAL 97
PRK03918 super family cl35229
DNA double-strand break repair ATPase Rad50;
5-195 9.37e-04

DNA double-strand break repair ATPase Rad50;


The actual alignment was detected with superfamily member PRK03918:

Pssm-ID: 235175 [Multi-domain]  Cd Length: 880  Bit Score: 43.90  E-value: 9.37e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    5 ERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESE---TRLYNKCQDLESLIQEKDDVIQNLELQLEEQKQIRIQEAKI 81
Cdd:PRK03918   216 LPELREELEKLEKEVKELEELKEEIEELEKELESLEgskRKLEEKIRELEERIEELKKEIEELEEKVKELKELKEKAEEY 295

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600   82 IEEKaaKIKEWVTVKLNELELENQNLRlinqnqtEEIRTMQSKLQEVQGKKSSTVSTLKLSEG--QRLSSL-TFGCFLSR 158
Cdd:PRK03918   296 IKLS--EFYEEYLDELREIEKRLSRLE-------EEINGIEERIKELEEKEERLEELKKKLKEleKRLEELeERHELYEE 366

                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 1034611600  159 ARSppqvvKSEEMSKISSKEPEFTEGKDMEEMEIPEK 195
Cdd:PRK03918   367 AKA-----KKEELERLKKRLTGLTPEKLEKELEELEK 398
 
Name Accession Description Interval E-value
FERM_F1_PLEKHH2 cd17179
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in pleckstrin ...
 1079-1181 6.49e-73

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in pleckstrin homology domain-containing family H member 2 (PLEKHH2); PLEKHH2 is a novel podocyte protein downregulated in human focal segmental glomerulosclerosis. It is highly enriched in renal glomerular podocytes, and acts as a novel, important component of the podocyte foot processes. PLEKHH2 contains a putative alpha-helical coiled-coil segment within the N-terminal half, and two Pleckstrin homology (PH) domains, a MyTH4 domain, and a FERM (Band 4.1, ezrin, radixin, moesin) domain within the C-terminal half. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). PLEKHH2 is involved in matrix adhesion and actin dynamics. It directly interacts through its FERM domain with the focal adhesion protein Hic-5 and actin.


Pssm-ID: 340699  Cd Length: 103  Bit Score: 237.56  E-value: 6.49e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600 1079 PFSIPVHFMNGIYQVVGFDASTTVEEFLNTLNQDTGMRKPAQSGFALFTDDPSGRDLEHCLQGNIKICDIISKWEQASKE 1158
Cdd:cd17179      1 PFSIPVHFMNGTYQVVGFDASTTVEEFLNTLNQDTGMRKPGQSGFALFTDDPSGKDLEHCLQGNIKICDIISKWEQASKE 80

                           90       100
                   ....*....|....*....|...
gi 1034611600 1159 QQPGKCEGTRTVRLTYKNRLYFS 1181
Cdd:cd17179     81 QHPGKCEGTRTVRLTYKNRLYFS 103
FERM_C-lobe_PLEKHH1_PLEKHH2 cd13206
FERM domain C-lobe of Pleckstrin homology domain-containing family H; PLEKHH1 and PLEKHH2 ...
 1309-1408 6.13e-62

FERM domain C-lobe of Pleckstrin homology domain-containing family H; 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 composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 241360  Cd Length: 100  Bit Score: 206.13  E-value: 6.13e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600 1309 GAKLFLAKPITPSSLGSTFLWLAVHEDGLSLLEYNSMRLIVSYVYKSLMTFGGYQDDFMVVINNTHSKDKPTEKLLFAMA 1388
Cdd:cd13206      1 GAKLFAAKPKTPSSLENTVVWLAVNEDGISILDYNTMRLVVTYPYSSVMTFGGCQDDFMLVVNSIKDKKKPTEKLLFAMA 80

                           90       100
                   ....*....|....*....|
gi 1034611600 1389 KPKILEITLLIASYINNFHQ 1408
Cdd:cd13206     81 KPKILEITLLIASYINAFHQ 100
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
 665-760 1.42e-51

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: 176.33  E-value: 1.42e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELSASCSILRGDNKQTVQLTTEKHTYYLTADSPNIL 744
Cdd:cd13282      1 KAGYLTKLGGKVKTWKRRWFVLKNGELFYYKSPNDVIRKPQGQIALDGSCEIARAEGAQTFEIVTEKRTYYLTADSENDL 80

                           90
                   ....*....|....*.
gi 1034611600  745 EEWIKVLQNVLRVQAA 760
Cdd:cd13282     81 DEWIRVIQNVLRRQAS 96
MyTH4 smart00139
Domain in Myosin and Kinesin Tails; Domain present twice in myosin-VIIa, and also present in 3 ...
 914-1069 4.83e-45

Domain in Myosin and Kinesin Tails; Domain present twice in myosin-VIIa, and also present in 3 other myosins.


Pssm-ID: 214535  Cd Length: 152  Bit Score: 159.83  E-value: 4.83e-45
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600   914 HSKEGIISPLTTLPSEALQTEAIKLFKTCQLFINAaVDSPAIDYHISLAQSALQICLTHPELQNEICCQLIKQTRRRqpQ 993
Cdd:smart00139    1 YTKDPIKTSLLKLESDELQKEAVKIFKAILKFMGD-IPLPRPDSHLDLVQFILQKGLDHPELRDEIYCQLIKQLTDN--P 77

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034611600   994 NQPGPLQGWQLLALCVGLFLPHHPFLWLLRLHLKRNADSRTeFGKYAIYCQRCVERTQQNGDREARPSRMEILSTL 1069
Cdd:smart00139   78 SRQSEERGWQLLYLCTSLFPPSERLLPYLLQFLSRRADPGS-EQGLAKYCLYRLERTLKNGARKQPPSRLELEAIL 152
MyTH4 pfam00784
MyTH4 domain; Domain in myosin and kinesin tails, present twice in myosin-VIIa, and also ...
 962-1067 5.69e-38

MyTH4 domain; Domain in myosin and kinesin tails, present twice in myosin-VIIa, and also present in 3 other myosins.


Pssm-ID: 459939  Cd Length: 105  Bit Score: 137.71  E-value: 5.69e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  962 AQSALQICLTHPELQNEICCQLIKQTRRRQpqNQPGPLQGWQLLALCVGLFLPHHPFLWLLRLHLKRNADSR-TEFGKYA 1040
Cdd:pfam00784    1 AQNILQKGLKRPELRDEIYCQLIKQTTNNP--KPESLLRGWQLLALCLGTFPPSKKLLKYLLKFLKRHADDPsREVGKYA 78

                           90       100
                   ....*....|....*....|....*..
gi 1034611600 1041 IYCQRCVERTQQNGDREARPSRMEILS 1067
Cdd:pfam00784   79 QFCLKRLKRTLKNGGRKYPPSREEIEA 105
B41 smart00295
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ...
 1082-1313 1.28e-29

Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in myosins, ezrin, radixin, moesin, protein tyrosine phosphatases. Plasma membrane-binding domain. These proteins play structural and regulatory roles in the assembly and stabilization of specialized plasmamembrane domains. Some PDZ domain containing proteins bind one or more of this family. Now includes JAKs.


Pssm-ID: 214604 [Multi-domain]  Cd Length: 201  Bit Score: 117.40  E-value: 1.28e-29
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  1082 IPVHFMNGIYQVVGFDASTTVEEFLNTLNQDTGMRkpAQSGFALFTDDPSGrDLEHCLQGNIKICDIISKWEqaskeqqp 1161
Cdd:smart00295    2 LKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIR--ESEYFGLQFEDPDE-DLRHWLDPAKTLLDQDVKSE-------- 70

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  1162 gkcegtrTVRLTYKNRLYFSVQARGETDREKLLLMY-QTNDQIINGLFPLNKDLALEMAALLSQVEIGDFERPFSTPAGH 1240
Cdd:smart00295   71 -------PLTLYFRVKFYPPDPNQLKEDPTRLNLLYlQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHDLRGE 143

                           170       180       190       200       210       220       230
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034611600  1241 VtnqckvnqtlkqVIEKFYPKRYRDGCSEEQLRqlcQRLSTRWMALRGHSAADCVRIYLTVARKWPFFGAKLF 1313
Cdd:smart00295  144 L------------SLKRFLPKQLLDSRKLKEWR---ERIVELHKELIGLSPEEAKLKYLELARKLPTYGVELF 201
FERM_M pfam00373
FERM central domain; This domain is the central structural domain of the FERM domain.
 1187-1313 7.71e-17

FERM central domain; This domain is the central structural domain of the FERM domain.


Pssm-ID: 459788 [Multi-domain]  Cd Length: 117  Bit Score: 77.69  E-value: 7.71e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600 1187 ETDREKLLLMYQTNDQIINGLFPLNKDLALEMAALLSQVEIGDFeRPFSTpaghvtnqckvnQTLKQVIEKFYPKRYrdg 1266
Cdd:pfam00373    7 QDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDY-QPSSH------------TSEYLSLESFLPKQL--- 70

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1034611600 1267 CSEEQLRQLCQRLSTRWMALRGHSAADCVRIYLTVARKWPFFGAKLF 1313
Cdd:pfam00373   71 LRKMKSKELEKRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 663-756 5.47e-16

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: 74.89  E-value: 5.47e-16
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600   663 LEKSGYLLKMS-GKVKSWKRRWFVLKGGELLYYKSPSDV-IRKPQGHIELSaSCSI------LRGDNKQTVQLTT-EKHT 733
Cdd:smart00233    1 VIKEGWLYKKSgGGKKSWKKRYFVLFNSTLLYYKSKKDKkSYKPKGSIDLS-GCTVreapdpDSSKKPHCFEIKTsDRKT 79

                            90       100
                    ....*....|....*....|...
gi 1034611600   734 YYLTADSPNILEEWIKVLQNVLR 756
Cdd:smart00233   80 LLLQAESEEEREKWVEALRKAIA 102
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 663-756 2.96e-15

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 72.98  E-value: 2.96e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  663 LEKSGYLLKMSGKVK-SWKRRWFVLKGGELLYYKSPSDVI-RKPQGHIELSASCSILRGDNKQT---------VQLTTEK 731
Cdd:pfam00169    1 VVKEGWLLKKGGGKKkSWKKRYFVLFDGSLLYYKDDKSGKsKEPKGSISLSGCEVVEVVASDSPkrkfcfelrTGERTGK 80

                           90       100
                   ....*....|....*....|....*
gi 1034611600  732 HTYYLTADSPNILEEWIKVLQNVLR 756
Cdd:pfam00169   81 RTYLLQAESEEERKDWIKAIQSAIR 105
FERM_B-lobe cd14473
FERM domain B-lobe; The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C ...
 1194-1305 7.08e-14

FERM domain B-lobe; 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 FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases, the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 271216  Cd Length: 99  Bit Score: 68.81  E-value: 7.08e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600 1194 LLMYQTNDQIINGLFPLNKDLALEMAALLSQVEIGDFERPFSTPaghvtnqckvnqtLKQVIEKFYPKRYRDGCSEEQLR 1273
Cdd:cd14473      4 LLYLQVKRDILEGRLPCSEETAALLAALALQAEYGDYDPSEHKP-------------KYLSLKRFLPKQLLKQRKPEEWE 70

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1034611600 1274 qlcQRLSTRWMALRGHSAADCVRIYLTVARKW 1305
Cdd:cd14473     71 ---KRIVELHKKLRGLSPAEAKLKYLKIARKL 99
PRK12704 PRK12704
phosphodiesterase; Provisional
 1-92 6.01e-06

phosphodiesterase; Provisional


Pssm-ID: 237177 [Multi-domain]  Cd Length: 520  Bit Score: 50.55  E-value: 6.01e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    1 MQQLERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESETRLYNKCQDLESLIQEKDDVIQNL-ELQLEEQKQIRIQ-- 77
Cdd:PRK12704    84 LQKLEKRLLQKEENLDRKLELLEKREEELEKKEKELEQKQQELEKKEEELEELIEEQLQELERIsGLTAEEAKEILLEkv 163

                           90
                   ....*....|....*
gi 1034611600   78 EAKIIEEKAAKIKEW 92
Cdd:PRK12704   164 EEEARHEAAVLIKEI 178
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 771-873 2.29e-05

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: 44.85  E-value: 2.29e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600   771 PTMKGLLTKVKHGYS---KRVWCTLIGKTLYYFRS---QEDKFPLGQIKLWEAKVEEVDRSCDSDEDyeasgrsllsthY 844
Cdd:smart00233    1 VIKEGWLYKKSGGGKkswKKRYFVLFNSTLLYYKSkkdKKSYKPKGSIDLSGCTVREAPDPDSSKKP------------H 68

                            90       100
                    ....*....|....*....|....*....
gi 1034611600   845 TIVIHPKDQGPTYLLIGSKHEKDTWLYHL 873
Cdd:smart00233   69 CFEIKTSDRKTLLLQAESEEEREKWVEAL 97
SMC_prok_A TIGR02169
chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of ...
 1-145 3.23e-05

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274009 [Multi-domain]  Cd Length: 1164  Bit Score: 48.53  E-value: 3.23e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    1 MQQLERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESETRLYN---KCQDLESLIQEKDDVIQNLELQLEEQKQ-IRI 76
Cdd:TIGR02169  711 LSDASRKIGEIEKEIEQLEQEEEKLKERLEELEEDLSSLEQEIENvksELKELEARIEELEEDLHKLEEALNDLEArLSH 790

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034611600   77 QEAKIIEEKAAKIKEWVT---VKLNELELENQNLRLINQNQTEEIRTMQSKLQEVQGKKSSTVSTLKLSEGQ 145
Cdd:TIGR02169  791 SRIPEIQAELSKLEEEVSrieARLREIEQKLNRLTLEKEYLEKEIQELQEQRIDLKEQIKSIEKEIENLNGK 862
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
1-129 8.69e-05

Uncharacterized protein, contains DUF3084 domain [Function unknown];


Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 46.43  E-value: 8.69e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    1 MQQLERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESETRLYNKCQDLESLIQEKDDVIQNLELQLEEQKQIRIQEAK 80
Cdd:COG4372     61 LEQLEEELEQARSELEQLEEELEELNEQLQAAQAELAQAQEELESLQEEAEELQEELEELQKERQDLEQQRKQLEAQIAE 140

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1034611600   81 IIEEKAAKIKEwvtvkLNELE-----LENQNLRLINQNQTEEIRTMQSKLQEVQ 129
Cdd:COG4372    141 LQSEIAEREEE-----LKELEeqlesLQEELAALEQELQALSEAEAEQALDELL 189
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
 770-832 1.20e-04

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: 43.00  E-value: 1.20e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034611600  770 KPTMKGLLTK---VKHGYSKRvWCTLIGKTLYYFRSQEDKFPLGQIKLWEAKVEevdrSCDSDEDY 832
Cdd:cd13288      7 PVDKEGYLWKkgeRNTSYQKR-WFVLKGNLLFYFEKKGDREPLGVIVLEGCTVE----LAEDAEPY 67
Myosin_tail_1 pfam01576
Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and ...
 2-140 3.07e-04

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types. This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament. The coiled-coil region provides the structural backbone the thick filament.


Pssm-ID: 460256 [Multi-domain]  Cd Length: 1081  Bit Score: 45.55  E-value: 3.07e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    2 QQLERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESE---TRLYNKCQDLEsliqekdDVIQNLELQLEE-------- 70
Cdd:pfam01576   22 QKAESELKELEKKHQQLCEEKNALQEQLQAETELCAEAEemrARLAARKQELE-------EILHELESRLEEeeersqql 94

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600   71 -------QKQIRIQEAKIIEEKAAKIK---EWVTV--KLNELE-----LENQNLRLINQNQ--TEEIRTMQSKLQEvQGK 131
Cdd:pfam01576   95 qnekkkmQQHIQDLEEQLDEEEAARQKlqlEKVTTeaKIKKLEedillLEDQNSKLSKERKllEERISEFTSNLAE-EEE 173


                   ....*....
gi 1034611600  132 KSSTVSTLK 140
Cdd:pfam01576  174 KAKSLSKLK 182
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 771-873 6.03e-04

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 40.62  E-value: 6.03e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  771 PTMKGLLTKVKHGYS---KRVWCTLIGKTLYYFRSQ---EDKFPLGQIKLWEAKVEEVDRSCDSDEDYeasgrsllstHY 844
Cdd:pfam00169    1 VVKEGWLLKKGGGKKkswKKRYFVLFDGSLLYYKDDksgKSKEPKGSISLSGCEVVEVVASDSPKRKF----------CF 70

                           90       100       110
                   ....*....|....*....|....*....|
gi 1034611600  845 TIVIHPKDQGPTYLLI-GSKHEKDTWLYHL 873
Cdd:pfam00169   71 ELRTGERTGKRTYLLQaESEEERKDWIKAI 100
PRK03918 PRK03918
DNA double-strand break repair ATPase Rad50;
5-195 9.37e-04

DNA double-strand break repair ATPase Rad50;


Pssm-ID: 235175 [Multi-domain]  Cd Length: 880  Bit Score: 43.90  E-value: 9.37e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    5 ERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESE---TRLYNKCQDLESLIQEKDDVIQNLELQLEEQKQIRIQEAKI 81
Cdd:PRK03918   216 LPELREELEKLEKEVKELEELKEEIEELEKELESLEgskRKLEEKIRELEERIEELKKEIEELEEKVKELKELKEKAEEY 295

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600   82 IEEKaaKIKEWVTVKLNELELENQNLRlinqnqtEEIRTMQSKLQEVQGKKSSTVSTLKLSEG--QRLSSL-TFGCFLSR 158
Cdd:PRK03918   296 IKLS--EFYEEYLDELREIEKRLSRLE-------EEINGIEERIKELEEKEERLEELKKKLKEleKRLEELeERHELYEE 366

                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 1034611600  159 ARSppqvvKSEEMSKISSKEPEFTEGKDMEEMEIPEK 195
Cdd:PRK03918   367 AKA-----KKEELERLKKRLTGLTPEKLEKELEELEK 398
SMC_N pfam02463
RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The ...
 4-203 1.91e-03

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.


Pssm-ID: 426784 [Multi-domain]  Cd Length: 1161  Bit Score: 43.04  E-value: 1.91e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    4 LERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESETRLYNKCQDL---ESLIQEKDDVIQNLELQLEEQKQIRIQEAK 80
Cdd:pfam02463  195 LKLQELKLKEQAKKALEYYQLKEKLELEEEYLLYLDYLKLNEERIDLlqeLLRDEQEEIESSKQEIEKEEEKLAQVLKEN 274

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600   81 IIEEKAAKIKEWVTVKLNELELENQNLRLINQNQTEEIRTMQSKLQEVQGKKSSTVSTLKLSEGQRLSSLTfgcFLSRAR 160
Cdd:pfam02463  275 KEEEKEKKLQEEELKLLAKEEEELKSELLKLERRKVDDEEKLKESEKEKKKAEKELKKEKEEIEELEKELK---ELEIKR 351

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1034611600  161 SPPQVVKSEEMSK----ISSKEPEFTEGKDMEEMEIPEKSVDNQVLE 203
Cdd:pfam02463  352 EAEEEEEEELEKLqeklEQLEEELLAKKKLESERLSSAAKLKEEELE 398
Mplasa_alph_rch TIGR04523
helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of ...
 2-200 5.50e-03

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.


Pssm-ID: 275316 [Multi-domain]  Cd Length: 745  Bit Score: 41.16  E-value: 5.50e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    2 QQLERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESE---TRLYNKCQDLESLIQEKDDVIQNLELQLEEQKQIRIQE 78
Cdd:TIGR04523  387 KNLESQINDLESKIQNQEKLNQQKDEQIKKLQQEKELLEkeiERLKETIIKNNSEIKDLTNQDSVKELIIKNLDNTRESL 466

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600   79 AKIIEEKAAKIKEwvtvklNELELENQNLRLINQNQ-----TEEIRTMQSKLQEVQGKKSStvstLKLSEgQRLSSLtfg 153
Cdd:TIGR04523  467 ETQLKVLSRSINK------IKQNLEQKQKELKSKEKelkklNEEKKELEEKVKDLTKKISS----LKEKI-EKLESE--- 532

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1034611600  154 cflsrarsppqvvKSEEMSKISSKEPEFTEGKDMEEMEIPEKSVDNQ 200
Cdd:TIGR04523  533 -------------KKEKESKISDLEDELNKDDFELKKENLEKEIDEK 566
 
Name Accession Description Interval E-value
FERM_F1_PLEKHH2 cd17179
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in pleckstrin ...
 1079-1181 6.49e-73

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in pleckstrin homology domain-containing family H member 2 (PLEKHH2); PLEKHH2 is a novel podocyte protein downregulated in human focal segmental glomerulosclerosis. It is highly enriched in renal glomerular podocytes, and acts as a novel, important component of the podocyte foot processes. PLEKHH2 contains a putative alpha-helical coiled-coil segment within the N-terminal half, and two Pleckstrin homology (PH) domains, a MyTH4 domain, and a FERM (Band 4.1, ezrin, radixin, moesin) domain within the C-terminal half. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). PLEKHH2 is involved in matrix adhesion and actin dynamics. It directly interacts through its FERM domain with the focal adhesion protein Hic-5 and actin.


Pssm-ID: 340699  Cd Length: 103  Bit Score: 237.56  E-value: 6.49e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600 1079 PFSIPVHFMNGIYQVVGFDASTTVEEFLNTLNQDTGMRKPAQSGFALFTDDPSGRDLEHCLQGNIKICDIISKWEQASKE 1158
Cdd:cd17179      1 PFSIPVHFMNGTYQVVGFDASTTVEEFLNTLNQDTGMRKPGQSGFALFTDDPSGKDLEHCLQGNIKICDIISKWEQASKE 80

                           90       100
                   ....*....|....*....|...
gi 1034611600 1159 QQPGKCEGTRTVRLTYKNRLYFS 1181
Cdd:cd17179     81 QHPGKCEGTRTVRLTYKNRLYFS 103
FERM_F1_PLEKHH1 cd17178
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in pleckstrin ...
 1079-1184 1.28e-65

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in pleckstrin homology domain-containing family H member 1 (PLEKHH1); PLEKHH1 is a homolog of Caenorhabditis elegans MAX-1 that has been implicated in motor neuron axon guidance. PLEKHH1 is critical in vascular patterning in vertebrate species through acting upstream of the ephrin pathway. PLEKHH1 contains a putative alpha-helical coiled-coil segment within the N-terminal half, and two Pleckstrin homology (PH) domains, a MyTH4 domain, and a FERM (Band 4.1, ezrin, radixin, moesin) domain within the C-terminal half. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).


Pssm-ID: 340698  Cd Length: 106  Bit Score: 216.75  E-value: 1.28e-65
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600 1079 PFSIPVHFMNGIYQVVGFDASTTVEEFLNTLNQDTGMRKPAQSGFALFTDDPSGRDLEHCLQGNIKICDIISKWEQASKE 1158
Cdd:cd17178      1 PFSIPVHFMNGTYQVVGFDGSTTVDEFLQTLNQETGMRKPSHSGFALFTDDPSGKDLEHCLQGSVKICDVISKWEQALKE 80

                           90       100
                   ....*....|....*....|....*.
gi 1034611600 1159 QQPGKCEGTRTVRLTYKNRLYFSVQA 1184
Cdd:cd17178     81 LHPGKYEGTRTVRLTYKSRLYFRAQA 106
FERM_C-lobe_PLEKHH1_PLEKHH2 cd13206
FERM domain C-lobe of Pleckstrin homology domain-containing family H; PLEKHH1 and PLEKHH2 ...
 1309-1408 6.13e-62

FERM domain C-lobe of Pleckstrin homology domain-containing family H; 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 composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 241360  Cd Length: 100  Bit Score: 206.13  E-value: 6.13e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600 1309 GAKLFLAKPITPSSLGSTFLWLAVHEDGLSLLEYNSMRLIVSYVYKSLMTFGGYQDDFMVVINNTHSKDKPTEKLLFAMA 1388
Cdd:cd13206      1 GAKLFAAKPKTPSSLENTVVWLAVNEDGISILDYNTMRLVVTYPYSSVMTFGGCQDDFMLVVNSIKDKKKPTEKLLFAMA 80

                           90       100
                   ....*....|....*....|
gi 1034611600 1389 KPKILEITLLIASYINNFHQ 1408
Cdd:cd13206     81 KPKILEITLLIASYINAFHQ 100
FERM_F1_Max1_like cd17094
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Caenorhabditis ...
 1079-1180 1.14e-60

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Caenorhabditis elegans max-1 and its homologs PLEKHH1 and PLEKHH2; Caenorhabditis elegans max-1 is expressed and functions in motor neurons. MAX-1 protein plays a possible role in netrin-induced axon repulsion by modulating the UNC-5 receptor signaling pathway. PLEKHH1 is critically required in vascular patterning in vertebrate species through acting upstream of the ephrin pathway. PLEKHH2 is highly enriched in renal glomerular podocytes, and acts as a novel, important component of the podocyte foot processes. It is involved in matrix adhesion and actin dynamics. Members in this family all contain two Pleckstrin homology (PH) domains, a MyTH4 domain, and a FERM (Band 4.1, ezrin, radixin, moesin) domain within the C-terminal half. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).


Pssm-ID: 340614  Cd Length: 102  Bit Score: 202.47  E-value: 1.14e-60
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600 1079 PFSIPVHFMNGIYQVVGFDASTTVEEFLNTLNQDTGMRKPAQSGFALFTDDPSGRDLEHCLQGNIKICDIISKWEQASKE 1158
Cdd:cd17094      1 PISIPVHLPNGTYQVVGFDGSTTVEEFLQTLNLELGIRPPSQSGFALFSDDPIGKDIEHCLQPSVKICDVISKWERASRE 80

                           90       100
                   ....*....|....*....|..
gi 1034611600 1159 QQPGKCEGTRTVRLTYKNRLYF 1180
Cdd:cd17094     81 AHSGKVDSSRVIRLTYKNRLYF 102
PH1_PLEKHH1_PLEKHH2 cd13282
Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) members 1 and 2 ...
 665-760 1.42e-51

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: 176.33  E-value: 1.42e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELSASCSILRGDNKQTVQLTTEKHTYYLTADSPNIL 744
Cdd:cd13282      1 KAGYLTKLGGKVKTWKRRWFVLKNGELFYYKSPNDVIRKPQGQIALDGSCEIARAEGAQTFEIVTEKRTYYLTADSENDL 80

                           90
                   ....*....|....*.
gi 1034611600  745 EEWIKVLQNVLRVQAA 760
Cdd:cd13282     81 DEWIRVIQNVLRRQAS 96
MyTH4 smart00139
Domain in Myosin and Kinesin Tails; Domain present twice in myosin-VIIa, and also present in 3 ...
 914-1069 4.83e-45

Domain in Myosin and Kinesin Tails; Domain present twice in myosin-VIIa, and also present in 3 other myosins.


Pssm-ID: 214535  Cd Length: 152  Bit Score: 159.83  E-value: 4.83e-45
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600   914 HSKEGIISPLTTLPSEALQTEAIKLFKTCQLFINAaVDSPAIDYHISLAQSALQICLTHPELQNEICCQLIKQTRRRqpQ 993
Cdd:smart00139    1 YTKDPIKTSLLKLESDELQKEAVKIFKAILKFMGD-IPLPRPDSHLDLVQFILQKGLDHPELRDEIYCQLIKQLTDN--P 77

                            90       100       110       120       130       140       150
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034611600   994 NQPGPLQGWQLLALCVGLFLPHHPFLWLLRLHLKRNADSRTeFGKYAIYCQRCVERTQQNGDREARPSRMEILSTL 1069
Cdd:smart00139   78 SRQSEERGWQLLYLCTSLFPPSERLLPYLLQFLSRRADPGS-EQGLAKYCLYRLERTLKNGARKQPPSRLELEAIL 152
MyTH4 pfam00784
MyTH4 domain; Domain in myosin and kinesin tails, present twice in myosin-VIIa, and also ...
 962-1067 5.69e-38

MyTH4 domain; Domain in myosin and kinesin tails, present twice in myosin-VIIa, and also present in 3 other myosins.


Pssm-ID: 459939  Cd Length: 105  Bit Score: 137.71  E-value: 5.69e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  962 AQSALQICLTHPELQNEICCQLIKQTRRRQpqNQPGPLQGWQLLALCVGLFLPHHPFLWLLRLHLKRNADSR-TEFGKYA 1040
Cdd:pfam00784    1 AQNILQKGLKRPELRDEIYCQLIKQTTNNP--KPESLLRGWQLLALCLGTFPPSKKLLKYLLKFLKRHADDPsREVGKYA 78

                           90       100
                   ....*....|....*....|....*..
gi 1034611600 1041 IYCQRCVERTQQNGDREARPSRMEILS 1067
Cdd:pfam00784   79 QFCLKRLKRTLKNGGRKYPPSREEIEA 105
B41 smart00295
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ...
 1082-1313 1.28e-29

Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in myosins, ezrin, radixin, moesin, protein tyrosine phosphatases. Plasma membrane-binding domain. These proteins play structural and regulatory roles in the assembly and stabilization of specialized plasmamembrane domains. Some PDZ domain containing proteins bind one or more of this family. Now includes JAKs.


Pssm-ID: 214604 [Multi-domain]  Cd Length: 201  Bit Score: 117.40  E-value: 1.28e-29
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  1082 IPVHFMNGIYQVVGFDASTTVEEFLNTLNQDTGMRkpAQSGFALFTDDPSGrDLEHCLQGNIKICDIISKWEqaskeqqp 1161
Cdd:smart00295    2 LKVYLLDGTTLEFEVDSSTTAEELLETVCRKLGIR--ESEYFGLQFEDPDE-DLRHWLDPAKTLLDQDVKSE-------- 70

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  1162 gkcegtrTVRLTYKNRLYFSVQARGETDREKLLLMY-QTNDQIINGLFPLNKDLALEMAALLSQVEIGDFERPFSTPAGH 1240
Cdd:smart00295   71 -------PLTLYFRVKFYPPDPNQLKEDPTRLNLLYlQVRNDILEGRLPCPEEEALLLAALALQAEFGDYDEELHDLRGE 143

                           170       180       190       200       210       220       230
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1034611600  1241 VtnqckvnqtlkqVIEKFYPKRYRDGCSEEQLRqlcQRLSTRWMALRGHSAADCVRIYLTVARKWPFFGAKLF 1313
Cdd:smart00295  144 L------------SLKRFLPKQLLDSRKLKEWR---ERIVELHKELIGLSPEEAKLKYLELARKLPTYGVELF 201
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 665-751 1.29e-20

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: 87.60  E-value: 1.29e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKV-KSWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELSASCSI---LRGDNKQTVQLTTEKH-TYYLTAD 739
Cdd:cd00821      1 KEGYLLKRGGGGlKSWKKRWFVLFEGVLLYYKSKKDSSYKPKGSIPLSGILEVeevSPKERPHCFELVTPDGrTYYLQAD 80

                           90
                   ....*....|..
gi 1034611600  740 SPNILEEWIKVL 751
Cdd:cd00821     81 SEEERQEWLKAL 92
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
 665-754 6.08e-18

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: 81.13  E-value: 6.08e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDvIRKPQGHIEL----SASCSILRGDNKQTVQLTTEKHTYYLTADS 740
Cdd:cd13215     23 KSGYLSKRSKRTLRYTRYWFVLKGDTLSWYNSSTD-LYFPAGTIDLryatSIELSKSNGEATTSFKIVTNSRTYKFKADS 101

                           90
                   ....*....|....
gi 1034611600  741 PNILEEWIKVLQNV 754
Cdd:cd13215    102 ETSADEWVKALKKQ 115
PH2_MyoX cd13296
Myosin X Pleckstrin homology (PH) domain, repeat 2; MyoX, a MyTH-FERM myosin, is a molecular ...
 665-756 2.38e-17

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: 78.66  E-value: 2.38e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKV-----KSWKRRWFVLKGGELLYYKSPSDViRKPQGHIELSASCSILRGDNKQT-VQLTTEKHTYYLTA 738
Cdd:cd13296      1 KSGWLTKKGGGSstlsrRNWKSRWFVLRDTVLKYYENDQEG-EKLLGTIDIRSAKEIVDNDPKENrLSITTEERTYHLVA 79

                           90
                   ....*....|....*...
gi 1034611600  739 DSPNILEEWIKVLQNVLR 756
Cdd:cd13296     80 ESPEDASQWVNVLTRVIS 97
FERM_M pfam00373
FERM central domain; This domain is the central structural domain of the FERM domain.
 1187-1313 7.71e-17

FERM central domain; This domain is the central structural domain of the FERM domain.


Pssm-ID: 459788 [Multi-domain]  Cd Length: 117  Bit Score: 77.69  E-value: 7.71e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600 1187 ETDREKLLLMYQTNDQIINGLFPLNKDLALEMAALLSQVEIGDFeRPFSTpaghvtnqckvnQTLKQVIEKFYPKRYrdg 1266
Cdd:pfam00373    7 QDEVTRHLLYLQAKDDILEGRLPCSEEEALLLAALQLQAEFGDY-QPSSH------------TSEYLSLESFLPKQL--- 70

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1034611600 1267 CSEEQLRQLCQRLSTRWMALRGHSAADCVRIYLTVARKWPFFGAKLF 1313
Cdd:pfam00373   71 LRKMKSKELEKRVLEAHKNLRGLSAEEAKLKYLQIAQSLPTYGVEFF 117
PH_TAAP2-like cd13255
Tandem PH-domain-containing protein 2 Pleckstrin homology (PH) domain; The binding of TAPP2 ...
 658-767 1.86e-16

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: 76.68  E-value: 1.86e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  658 GKNEPLEKSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSD--VIRK-PQGHIELSASCSILRGDNkqTVQLTTEKHTY 734
Cdd:cd13255      1 MISEAVLKAGYLEKKGERRKTWKKRWFVLRPTKLAYYKNDKEyrLLRLiDLTDIHTCTEVQLKKHDN--TFGIVTPARTF 78

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1034611600  735 YLTADSPNILEEWIKVLqNVLRVQAANPLSLQP 767
Cdd:cd13255     79 YVQADSKAEMESWISAI-NLARQALRATITPNT 110
PH_RhoGap25-like cd13263
Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; ...
 665-755 1.94e-16

Rho GTPase activating protein 25 and related proteins Pleckstrin homology (PH) domain; RhoGAP25 (also called ArhGap25) like other RhoGaps are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. This hierarchy contains RhoGAP22, RhoGAP24, and RhoGAP25. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) 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: 270083  Cd Length: 114  Bit Score: 76.65  E-value: 1.94e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDVirKPQGHIELSASC----------------SILRGDNKQtvQLT 728
Cdd:cd13263      5 KSGWLKKQGSIVKNWQQRWFVLRGDQLYYYKDEDDT--KPQGTIPLPGNKvkevpfnpeepgkflfEIIPGGGGD--RMT 80

                           90       100
                   ....*....|....*....|....*..
gi 1034611600  729 TEKHTYYLTADSPNILEEWIKVLQNVL 755
Cdd:cd13263     81 SNHDSYLLMANSQAEMEEWVKVIRRVI 107
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 663-756 5.47e-16

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: 74.89  E-value: 5.47e-16
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600   663 LEKSGYLLKMS-GKVKSWKRRWFVLKGGELLYYKSPSDV-IRKPQGHIELSaSCSI------LRGDNKQTVQLTT-EKHT 733
Cdd:smart00233    1 VIKEGWLYKKSgGGKKSWKKRYFVLFNSTLLYYKSKKDKkSYKPKGSIDLS-GCTVreapdpDSSKKPHCFEIKTsDRKT 79

                            90       100
                    ....*....|....*....|...
gi 1034611600   734 YYLTADSPNILEEWIKVLQNVLR 756
Cdd:smart00233   80 LLLQAESEEEREKWVEALRKAIA 102
PH_DAPP1 cd10573
Dual Adaptor for Phosphotyrosine and 3-Phosphoinositides Pleckstrin homology (PH) domain; ...
 665-752 8.51e-16

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: 74.28  E-value: 8.51e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDVirKPQGHIELSASCSILRGDNKQTV---QLTTEKHTYYLTADSP 741
Cdd:cd10573      5 KEGYLTKLGGIVKNWKTRWFVLRRNELKYFKTRGDT--KPIRVLDLRECSSVQRDYSQGKVncfCLVFPERTFYMYANTE 82

                           90
                   ....*....|.
gi 1034611600  742 NILEEWIKVLQ 752
Cdd:cd10573     83 EEADEWVKLLK 93
FERM_F1_DdMyo7_like cd17208
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Dictyostelium ...
 1084-1180 1.03e-15

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in Dictyostelium discoideum Myosin-VIIa (DdMyo7) and similar proteins; DdMyo7, also termed Myosin-I heavy chain, or class VII unconventional myosin, or M7, plays a role in adhesion in Dictyostelium where it is a component of a complex of proteins that serve to link membrane receptors to the underlying actin cytoskeleton. It interacts with talinA, an actin-binding protein with a known role in cell-substrate adhesion. DdMyo7 is required for phagocytosis. It is also essential for the extension of filopodia, plasma membrane protrusions filled with parallel bundles of F-actin. Members in this family contain a myosin motor domain, two MyTH4 domains, two FERM (Band 4.1, ezrin, radixin, moesin) domains, and two Pleckstrin homology (PH) domains. Some family members contain an extra SH3 domain. Each FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).


Pssm-ID: 340728  Cd Length: 98  Bit Score: 73.82  E-value: 1.03e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600 1084 VHFMNGIYQVVGFDASTTVEEFLNTLNQDTGMRKPAQsGFALFTDDPsgrDLEHCLQGNIKICDIISKWEQASKEQqpGK 1163
Cdd:cd17208      8 FYFLDGQFKALEFDSAATAAEVLEQLKQKIGLRSTAD-GFALYEVFG---GIERAILPEEKVADVLSKWEKLQRTM--AS 81

                           90
                   ....*....|....*..
gi 1034611600 1164 CEGTRTVRLTYKNRLYF 1180
Cdd:cd17208     82 CAAQQAVKFVFKKRLFF 98
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 663-756 2.96e-15

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 72.98  E-value: 2.96e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  663 LEKSGYLLKMSGKVK-SWKRRWFVLKGGELLYYKSPSDVI-RKPQGHIELSASCSILRGDNKQT---------VQLTTEK 731
Cdd:pfam00169    1 VVKEGWLLKKGGGKKkSWKKRYFVLFDGSLLYYKDDKSGKsKEPKGSISLSGCEVVEVVASDSPkrkfcfelrTGERTGK 80

                           90       100
                   ....*....|....*....|....*
gi 1034611600  732 HTYYLTADSPNILEEWIKVLQNVLR 756
Cdd:pfam00169   81 RTYLLQAESEEERKDWIKAIQSAIR 105
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
 660-751 4.19e-15

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: 72.31  E-value: 4.19e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  660 NEPLEKSGYLLKMSGK-VKSWKRRWFVLKGGELLYYKSPSDviRKPQGHIEL-SASCSILRGDNKqtvqlTTEKH----- 732
Cdd:cd13248      4 NAPVVMSGWLHKQGGSgLKNWRKRWFVLKDNCLYYYKDPEE--EKALGSILLpSYTISPAPPSDE-----ISRKFafkae 76

                           90       100
                   ....*....|....*....|....
gi 1034611600  733 -----TYYLTADSPNILEEWIKVL 751
Cdd:cd13248     77 hanmrTYYFAADTAEEMEQWMNAM 100
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
 660-753 5.79e-15

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: 72.66  E-value: 5.79e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  660 NEPLEKSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDviRKPQGHIELsASCSI--LRGDNKQTVQLTT---EKHTY 734
Cdd:cd13288      5 NSPVDKEGYLWKKGERNTSYQKRWFVLKGNLLFYFEKKGD--REPLGVIVL-EGCTVelAEDAEPYAFAIRFdgpGARSY 81

                           90
                   ....*....|....*....
gi 1034611600  735 YLTADSPNILEEWIKVLQN 753
Cdd:cd13288     82 VLAAENQEDMESWMKALSR 100
PH_AtPH1 cd13276
Arabidopsis thaliana Pleckstrin homolog (PH) 1 (AtPH1) PH domain; AtPH1 is expressed in all ...
 665-748 9.01e-15

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: 71.58  E-value: 9.01e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPsDVIR--KPQGHIELSaSCSILRGD----NKQ-TVQLTTEKHTYYLT 737
Cdd:cd13276      1 KAGWLEKQGEFIKTWRRRWFVLKQGKLFWFKEP-DVTPysKPRGVIDLS-KCLTVKSAedatNKEnAFELSTPEETFYFI 78

                           90
                   ....*....|.
gi 1034611600  738 ADSPNILEEWI 748
Cdd:cd13276     79 ADNEKEKEEWI 89
PH_GRP1-like cd01252
General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 ...
 664-755 5.28e-14

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: 69.65  E-value: 5.28e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  664 EKSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDviRKPQGHIELS------------ASCSILRGD-NKQTVQ---- 726
Cdd:cd01252      4 DREGWLLKLGGRVKSWKRRWFILTDNCLYYFEYTTD--KEPRGIIPLEnlsvrevedkkkPFCFELYSPsNGQVIKackt 81

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1034611600  727 -----LTTEKHT-YYLTADSPNILEEWIKVLQNVL 755
Cdd:cd01252     82 dsdgkVVEGNHTvYRISAASEEERDEWIKSIKASI 116
PH_SWAP-70 cd13273
Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called ...
 665-758 6.23e-14

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: 69.25  E-value: 6.23e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDviRKPQGHIELSASCSI----LRGDNKQTVQLTTEKHTYYLTADS 740
Cdd:cd13273     10 KKGYLWKKGHLLPTWTERWFVLKPNSLSYYKSEDL--KEKKGEIALDSNCCVeslpDREGKKCRFLVKTPDKTYELSASD 87

                           90
                   ....*....|....*...
gi 1034611600  741 PNILEEWIKVLQNVLRVQ 758
Cdd:cd13273     88 HKTRQEWIAAIQTAIRLS 105
PH_Sbf1_hMTMR5 cd01235
Set binding factor 1 (also called Human MTMR5) Pleckstrin Homology (PH) domain; Sbf1 is a ...
 667-755 6.67e-14

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: 69.28  E-value: 6.67e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  667 GYLLKMSGKVKSWKRRWFVLKGG--ELLYYKSPSDviRKPQGHIELSASCSI----------LRGDNKQTVQLTTEKHTY 734
Cdd:cd01235      7 GYLYKRGALLKGWKQRWFVLDSTkhQLRYYESRED--TKCKGFIDLAEVESVtpatpiigapKRADEGAFFDLKTNKRVY 84

                           90       100
                   ....*....|....*....|.
gi 1034611600  735 YLTADSPNILEEWIKVLQNVL 755
Cdd:cd01235     85 NFCAFDAESAQQWIEKIQSCL 105
FERM_B-lobe cd14473
FERM domain B-lobe; The FERM domain has a cloverleaf tripart structure (FERM_N, FERM_M, FERM_C ...
 1194-1305 7.08e-14

FERM domain B-lobe; 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 FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases, the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the pleckstrin homology (PH) and phosphotyrosine binding (PTB) domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 271216  Cd Length: 99  Bit Score: 68.81  E-value: 7.08e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600 1194 LLMYQTNDQIINGLFPLNKDLALEMAALLSQVEIGDFERPFSTPaghvtnqckvnqtLKQVIEKFYPKRYRDGCSEEQLR 1273
Cdd:cd14473      4 LLYLQVKRDILEGRLPCSEETAALLAALALQAEYGDYDPSEHKP-------------KYLSLKRFLPKQLLKQRKPEEWE 70

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1034611600 1274 qlcQRLSTRWMALRGHSAADCVRIYLTVARKW 1305
Cdd:cd14473     71 ---KRIVELHKKLRGLSPAEAKLKYLKIARKL 99
PH1_PH_fungal cd13298
Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal ...
 665-756 1.39e-13

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: 68.04  E-value: 1.39e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDviRKPQGHIELS--ASCSILRGDNKQTV-QLTTEKHTYYLTADSP 741
Cdd:cd13298      8 KSGYLLKRSRKTKNWKKRWVVLRPCQLSYYKDEKE--YKLRRVINLSelLAVAPLKDKKRKNVfGIYTPSKNLHFRATSE 85

                           90
                   ....*....|....*
gi 1034611600  742 NILEEWIKVLQNVLR 756
Cdd:cd13298     86 KDANEWVEALREEFR 100
PH_ACAP cd13250
ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP ...
 665-754 1.48e-13

ArfGAP with coiled-coil, ankyrin repeat and PH domains Pleckstrin homology (PH) domain; ACAP (also called centaurin beta) functions both as a Rab35 effector and as an Arf6-GTPase-activating protein (GAP) by which it controls actin remodeling and membrane trafficking. ACAP contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain, a phospholipid-binding domain, a PH domain, a GAP domain, and four ankyrin repeats. The AZAPs constitute a family of Arf GAPs that are characterized by an NH2-terminal pleckstrin homology (PH) domain and a central Arf GAP domain followed by two or more ankyrin repeats. On the basis of sequence and domain organization, the AZAP family is further subdivided into four subfamilies: 1) the ACAPs contain an NH2-terminal bin/amphiphysin/Rvs (BAR) domain (a phospholipid-binding domain that is thought to sense membrane curvature), a single PH domain followed by the GAP domain, and four ankyrin repeats; 2) the ASAPs also contain an NH2-terminal BAR domain, the tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 domain; 3) the AGAPs contain an NH2-terminal GTPase-like domain (GLD), a split PH domain, and the GAP domain followed by four ankyrin repeats; and 4) the ARAPs contain both an Arf GAP domain and a Rho GAP domain, as well as an NH2-terminal sterile-a motif (SAM), a proline-rich region, a GTPase-binding domain, and five PH domains. PMID 18003747 and 19055940 Centaurin can bind to phosphatidlyinositol (3,4,5)P3. 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: 270070  Cd Length: 98  Bit Score: 68.01  E-value: 1.48e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKV-KSWKRRWFVLKGGELLYYKspsdvirKPQGHIELSASCSILRGdnkqTVQLTTEKH----------- 732
Cdd:cd13250      1 KEGYLFKRSSNAfKTWKRRWFSLQNGQLYYQK-------RDKKDEPTVMVEDLRLC----TVKPTEDSDrrfcfevispt 69

                           90       100
                   ....*....|....*....|...
gi 1034611600  733 -TYYLTADSPNILEEWIKVLQNV 754
Cdd:cd13250     70 kSYMLQAESEEDRQAWIQAIQSA 92
PH_RASA1 cd13260
RAS p21 protein activator (GTPase activating protein) 1 Pleckstrin homology (PH) domain; RASA1 ...
 662-752 2.92e-13

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: 67.37  E-value: 2.92e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  662 PLEKSGYLLKMSGKVKSWKRRWFVLKGGE--LLYYKSPSDVirKPQGHIELSaSCSIL--------RGDNKQTV-QLTTE 730
Cdd:cd13260      2 GIDKKGYLLKKGGKNKKWKNLYFVLEGKEqhLYFFDNEKRT--KPKGLIDLS-YCSLYpvhdslfgRPNCFQIVvRALNE 78

                           90       100
                   ....*....|....*....|..
gi 1034611600  731 KHTYYLTADSPNILEEWIKVLQ 752
Cdd:cd13260     79 STITYLCADTAELAQEWMRALR 100
PH_TBC1D2A cd01265
TBC1 domain family member 2A pleckstrin homology (PH) domain; TBC1D2A (also called PARIS-1 ...
 666-752 2.96e-13

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: 66.96  E-value: 2.96e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  666 SGYLLKMSGK---VKSWKRRWFVLKGG--ELLYYKSPSDVirKPQGHIELS-ASCSILRGDNKQTVQLTTEKHTYYLTAD 739
Cdd:cd01265      3 CGYLNKLETRglgLKGWKRRWFVLDESkcQLYYYRSPQDA--TPLGSIDLSgAAFSYDPEAEPGQFEIHTPGRVHILKAS 80

                           90
                   ....*....|...
gi 1034611600  740 SPNILEEWIKVLQ 752
Cdd:cd01265     81 TRQAMLYWLQALQ 93
PH_RhoGAP2 cd13378
Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 ...
 661-755 1.67e-12

Rho GTPase activating protein 2 Pleckstrin homology (PH) domain; RhoGAP2 (also called RhoGap22 or ArhGap22) are involved in cell polarity, cell morphology and cytoskeletal organization. They activate a GTPase belonging to the RAS superfamily of small GTP-binding proteins. The encoded protein is insulin-responsive, is dependent on the kinase Akt, and requires the Akt-dependent 14-3-3 binding protein which binds sequentially to two serine residues resulting in regulation of cell motility. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) 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: 241529  Cd Length: 116  Bit Score: 65.35  E-value: 1.67e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  661 EPLEKSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDVirKPQGHIELSAS----------------CSILRGDNKQT 724
Cdd:cd13378      1 EGVLKAGWLKKQRSIMKNWQQRWFVLRGDQLFYYKDEEET--KPQGCISLQGSqvnelppnpeepgkhlFEILPGGAGDR 78

                           90       100       110
                   ....*....|....*....|....*....|.
gi 1034611600  725 VQLTTEKHTYYLTADSPNILEEWIKVLQNVL 755
Cdd:cd13378     79 EKVPMNHEAFLLMANSQSDMEDWVKAIRRVI 109
PH_RhoGap24 cd13379
Rho GTPase activating protein 24 Pleckstrin homology (PH) domain; RhoGap24 (also called ...
 665-755 1.61e-11

Rho GTPase activating protein 24 Pleckstrin homology (PH) domain; RhoGap24 (also called ARHGAP24, p73RhoGAp, and Filamin-A-associated RhoGAP) like other RhoGAPs are involved in cell polarity, cell morphology and cytoskeletal organization. They act as GTPase activators for the Rac-type GTPases by converting them to an inactive GDP-bound state and control actin remodeling by inactivating Rac downstream of Rho leading to suppress leading edge protrusion and promotes cell retraction to achieve cellular polarity and are able to suppress RAC1 and CDC42 activity in vitro. Overexpression of these proteins induces cell rounding with partial or complete disruption of actin stress fibers and formation of membrane ruffles, lamellipodia, and filopodia. Members here contain an N-terminal PH domain followed by a RhoGAP domain and either a BAR or TATA Binding Protein (TBP) Associated Factor 4 (TAF4) 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: 241530  Cd Length: 114  Bit Score: 62.68  E-value: 1.61e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDVirKPQGHIELSAS------CS----------ILRGDNKQtvQLT 728
Cdd:cd13379      5 KCGWLRKQGGFVKTWHTRWFVLKGDQLYYFKDEDET--KPLGTIFLPGNrvtehpCNeeepgkflfeVVPGGDRE--RMT 80

                           90       100
                   ....*....|....*....|....*..
gi 1034611600  729 TEKHTYYLTADSPNILEEWIKVLQNVL 755
Cdd:cd13379     81 ANHETYLLMASTQNDMEDWVKSIRRVI 107
PH_ORP3_ORP6_ORP7 cd13287
Human Oxysterol binding protein related proteins 3, 6, and 7 Pleckstrin homology (PH) domain; ...
 659-752 3.44e-11

Human Oxysterol binding protein related proteins 3, 6, and 7 Pleckstrin homology (PH) domain; Human ORP3 is proposed to function in regulating the cell-matrix and cell-cell adhesion. A proposed specific function for Human ORP6 was not found at present. Human ORP7is proposed to function in negatively regulating the Golgi soluble NSF attachment protein receptor (SNARE) of 28kDa (GS28) protein stability via sequestration of Golgi-associated ATPase enhancer of 16 kDa (GATE-16). ORP3 has 2 isoforms: the longer ORP3(1) and the shorter ORP3(2). ORP3(1), ORP6, and ORP7 all contain a N-terminal PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. The shorter ORP3(2) is missing the C-terminal portion of its 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: 270104  Cd Length: 123  Bit Score: 61.96  E-value: 3.44e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  659 KNEPLEKSGYLLKM-SGKVKSWKRRWFVLKGGELLYYKSPSDVIR-KPQGHIELSASC-SILRgdNKQTVQLTTEKHTYY 735
Cdd:cd13287     18 VQEPGKQEGYLLKKrKWPLKGWHKRFFVLEKGILKYAKSPLDIAKgKLHGSIDVGLSVmSIKK--KARRIDLDTEEFIYH 95

                           90
                   ....*....|....*..
gi 1034611600  736 LTADSPNILEEWIKVLQ 752
Cdd:cd13287     96 LKVKSQDLFDSWVAKLR 112
PH1_ARAP cd13253
ArfGAP with RhoGAP domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain, ...
 664-758 1.87e-10

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


Pssm-ID: 270073  Cd Length: 94  Bit Score: 58.94  E-value: 1.87e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  664 EKSGYLLKMSGK--VKSWKRRWFVLKGGELLYYKSPSDVIRKpqGHIELSA-SCSILRGDNKqtVQLTTEKHTYYLTADS 740
Cdd:cd13253      1 IKSGYLDKQGGQgnNKGFQKRWVVFDGLSLRYFDSEKDAYSK--RIIPLSAiSTVRAVGDNK--FELVTTNRTFVFRAES 76

                           90
                   ....*....|....*...
gi 1034611600  741 PNILEEWIKVLQNVLRVQ 758
Cdd:cd13253     77 DDERNLWCSTLQAAISEY 94
PH1_Pleckstrin_2 cd13301
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in ...
 665-756 3.14e-10

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: 58.54  E-value: 3.14e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDviRKPQGHIEL---SASCSILRGDNKQTV-QLTTEK-HTYYLTAD 739
Cdd:cd13301      5 KEGYLVKKGHVVNNWKARWFVLKEDGLEYYKKKTD--SSPKGMIPLkgcTITSPCLEYGKRPLVfKLTTAKgQEHFFQAC 82

                           90
                   ....*....|....*..
gi 1034611600  740 SPNILEEWIKVLQNVLR 756
Cdd:cd13301     83 SREERDAWAKDITKAIT 99
PH_evt cd13265
Evectin Pleckstrin homology (PH) domain; There are 2 members of the evectin family (also ...
 661-754 5.74e-10

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: 58.08  E-value: 5.74e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  661 EPLEKSGYLLKMSGKVKSWKRRWFVLKG-GELLYYKSPSDviRKPQGHIELSASC-SILRGDNKQTVQL----------- 727
Cdd:cd13265      1 MALVKSGWLLRQSTILKRWKKNWFVLYGdGNLVYYEDETR--REVEGRINMPRECrNIRVGLECRDVQPpegrsrdcllq 78

                           90       100
                   ....*....|....*....|....*....
gi 1034611600  728 --TTEKHTYYLTADSPNILEEWIKVLQNV 754
Cdd:cd13265     79 ivLRDGSTLFLCAESADDALAWKLALQDA 107
FERM_C-lobe cd00836
FERM domain C-lobe; The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N ...
 1309-1407 7.25e-10

FERM domain C-lobe; The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 275389  Cd Length: 93  Bit Score: 57.00  E-value: 7.25e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600 1309 GAKLFLAKPItpSSLGSTfLWLAVHEDGLSLLEYNSMRLIVSYVYK--SLMTFGGyQDDFMVVINNthskDKPTEKLLFA 1386
Cdd:cd00836      1 GVEFFPVKDK--SKKGSP-IILGVNPEGISVYDELTGQPLVLFPWPniKKISFSG-AKKFTIVVAD----EDKQSKLLFQ 72

                           90       100
                   ....*....|....*....|.
gi 1034611600 1387 MAKPKILEITLLIASYINNFH 1407
Cdd:cd00836     73 TPSRQAKEIWKLIVGYHRFLL 93
PH_3BP2 cd13308
SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes ...
 665-754 9.06e-10

SH3 domain-binding protein 2 Pleckstrin homology (PH) domain; SH3BP2 (the gene that encodes the adaptor protein 3BP2), HD, ITU, IT10C3, and ADD1 are located near the Huntington's Disease Gene on Human Chromosome 4pl6.3. SH3BP2 lies in a region that is often missing in individuals with Wolf-Hirschhorn syndrome (WHS). Gain of function mutations in SH3BP2 causes enhanced B-cell antigen receptor (BCR)-mediated activation of nuclear factor of activated T cells (NFAT), resulting in a rare, genetic disorder called cherubism. This results in an increase in the signaling complex formation with Syk, phospholipase C-gamma2 (PLC-gamma2), and Vav1. It was recently discovered that Tankyrase regulates 3BP2 stability through ADP-ribosylation and ubiquitylation by the E3-ubiquitin ligase. Cherubism mutations uncouple 3BP2 from Tankyrase-mediated protein destruction, which results in its stabilization and subsequent hyperactivation of the Src, Syk, and Vav signaling pathways. SH3BP2 is also a potential negative regulator of the abl oncogene. 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: 270118  Cd Length: 113  Bit Score: 57.42  E-value: 9.06e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKVKS---WKRRWFVLKGGELLYYKSPSDVirKPQGHIELS-ASCSI---LRGDNK---QTVQLTTEKHTY 734
Cdd:cd13308     11 HSGTLTKKGGSQKTlqnWQLRYVIIHQGCVYYYKNDQSA--KPKGVFSLNgYNRRAaeeRTSKLKfvfKIIHLSPDHRTW 88

                           90       100
                   ....*....|....*....|
gi 1034611600  735 YLTADSPNILEEWIKVLQNV 754
Cdd:cd13308     89 YFAAKSEDEMSEWMEYIRRE 108
PH_M-RIP cd13275
Myosin phosphatase-RhoA Interacting Protein Pleckstrin homology (PH) domain; M-RIP is proposed ...
 665-754 3.25e-09

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: 55.80  E-value: 3.25e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDVIRK-PQGHIELS--ASCSILRGDNKQTVQLTT-EKHTYYLTADS 740
Cdd:cd13275      1 KKGWLMKQGSRQGEWSKHWFVLRGAALKYYRDPSAEEAGeLDGVIDLSscTEVTELPVSRNYGFQVKTwDGKVYVLSAMT 80

                           90
                   ....*....|....
gi 1034611600  741 PNILEEWIKVLQNV 754
Cdd:cd13275     81 SGIRTNWIQALRKA 94
PH3_MyoX-like cd13297
Myosin X-like Pleckstrin homology (PH) domain, repeat 3; MyoX, a MyTH-FERM myosin, is a ...
 652-755 4.17e-09

Myosin X-like Pleckstrin homology (PH) domain, repeat 3; 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 third MyoX PH repeat. PLEKHH3/Pleckstrin homology (PH) domain containing, family H (with MyTH4 domain) member 3 is also part of this CD and like MyoX contains a FERM domain, a MyTH4 domain, and a single PH domain. Not much is known about the function of PLEKHH3. 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: 270109  Cd Length: 126  Bit Score: 55.90  E-value: 4.17e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  652 SSSSDNGKNEPLEKsGYLLKMSGK--VKSW---KRRWFVLKGGELLYYKSPSDVIRKpQGHIELSASCSILRGDNKQ--- 723
Cdd:cd13297      3 KGDLDEGGQDVIER-GWLYKEGGKggARGNltkKKRWFVLTGNSLDYYKSSEKNSLK-LGTLVLNSLCSVVPPDEKMake 80

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1034611600  724 ----TVQLTTEKHTYYLTADSPNILEEWIKVLQNVL 755
Cdd:cd13297     81 tgywTFTVHGRKHSFRLYTKLQEEAMRWVNAIQDVI 116
PH_Osh1p_Osh2p_yeast cd13292
Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p ...
 662-756 7.51e-09

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: 54.62  E-value: 7.51e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  662 PLEKSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELSAscSILRGDNKQTVQL-----TTEKHTYYL 736
Cdd:cd13292      1 PPTMKGYLKKWTNYAKGYKTRWFVLEDGVLSYYRHQDDEGSACRGSINMKN--ARLVSDPSEKLRFevsskTSGSPKWYL 78

                           90       100
                   ....*....|....*....|
gi 1034611600  737 TADSPNILEEWIKVLQNVLR 756
Cdd:cd13292     79 KANHPVEAARWIQALQKAIE 98
PH2_TAPP1_2 cd13271
Tandem PH-domain-containing proteins 1 and 2 Pleckstrin homology (PH) domain, C-terminal ...
 665-749 8.99e-09

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: 54.67  E-value: 8.99e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDviRKPQGHIEL-----SASC---SILRGDNkqTVQLTTEKHTYYL 736
Cdd:cd13271     10 KSGYCVKQGAVRKNWKRRFFILDDNTISYYKSETD--KEPLRTIPLrevlkVHEClvkSLLMRDN--LFEIITTSRTFYI 85

                           90
                   ....*....|...
gi 1034611600  737 TADSPNILEEWIK 749
Cdd:cd13271     86 QADSPEEMHSWIK 98
PH2_ADAP cd01251
ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2; ADAP (also called ...
 665-755 2.58e-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: 52.98  E-value: 2.58e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKVK-SWKRRWFVLKGGELLYYKSPSDVIRKPQ---GHIELSASCSI-----LRGDNKQTVQLTTEKHTYY 735
Cdd:cd01251      4 KEGYLEKTGPKQTdGFRKRWFTLDDRRLMYFKDPLDAFPKGEifiGSKEEGYSVREglppgIKGHWGFGFTLVTPDRTFL 83

                           90       100
                   ....*....|....*....|
gi 1034611600  736 LTADSPNILEEWIKVLQNVL 755
Cdd:cd01251     84 LSAETEEERREWITAIQKVL 103
PH_IRS cd01257
Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate ...
 665-756 2.62e-08

Insulin receptor substrate (IRS) pleckstrin homology (PH) domain; Insulin receptor substrate (IRS) molecules are mediators in insulin signaling and play a role in maintaining basic cellular functions such as growth and metabolism. They act as docking proteins between the insulin receptor and a complex network of intracellular signaling molecules containing Src homology 2 (SH2) domains. Four members (IRS-1, IRS-2, IRS-3, IRS-4) of this family have been identified that differ as to tissue distribution, subcellular localization, developmental expression, binding to the insulin receptor, and interaction with SH2 domain-containing proteins. IRS molecules have an N-terminal PH domain, followed by an IRS-like PTB domain which has a PH-like fold. 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.cytoskeletal associated molecules, and in lipid associated enzymes.


Pssm-ID: 269959  Cd Length: 106  Bit Score: 53.06  E-value: 2.62e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLlkmsGKVKSWKRRWFVLKGGE------LLYYKSPSDVIRK--PQGHIELSASCSILR---GDNKQTVQLTTEKHT 733
Cdd:cd01257      5 KSGYL----KKLKTMRKRYFVLRAEShggparLEYYENEKKFRRNaePKRVIPLSSCFNINKradAKHKHLIALYTKDEC 80

                           90       100
                   ....*....|....*....|...
gi 1034611600  734 YYLTADSPNILEEWIKVLQNVLR 756
Cdd:cd01257     81 FGLVAESEEEQDEWYQALLELQR 103
PH_OSBP_ORP4 cd13284
Human Oxysterol binding protein and OSBP-related protein 4 Pleckstrin homology (PH) domain; ...
 665-753 2.78e-08

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: 52.77  E-value: 2.78e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELSASCsILRGDNKQTVQLTTEKHTYYLTADSPNIL 744
Cdd:cd13284      1 MKGWLLKWTNYIKGYQRRWFVLSNGLLSYYRNQAEMAHTCRGTINLAGAE-IHTEDSCNFVISNGGTQTFHLKASSEVER 79


                   ....*....
gi 1034611600  745 EEWIKVLQN 753
Cdd:cd13284     80 QRWVTALEL 88
PH_Boi cd13316
Boi family Pleckstrin homology domain; Yeast Boi proteins Boi1 and Boi2 are functionally ...
 666-751 3.06e-08

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: 52.76  E-value: 3.06e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  666 SGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDVIRKpqGHIELSAScSILRGDN------KQTVQLT--TEKHTYYLT 737
Cdd:cd13316      3 SGWMKKRGERYGTWKTRYFVLKGTRLYYLKSENDDKEK--GLIDLTGH-RVVPDDSnspfrgSYGFKLVppAVPKVHYFA 79

                           90
                   ....*....|....
gi 1034611600  738 ADSPNILEEWIKVL 751
Cdd:cd13316     80 VDEKEELREWMKAL 93
PH_GPBP cd13283
Goodpasture antigen binding protein Pleckstrin homology (PH) domain; The GPBP (also called ...
 665-752 3.51e-08

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: 52.67  E-value: 3.51e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELSaSCSI-------LRGDnkqtvqLTTEKHTYYLT 737
Cdd:cd13283      1 LRGVLSKWTNYIHGWQDRYFVLKDGTLSYYKSESEKEYGCRGSISLS-KAVIkphefdeCRFD------VSVNDSVWYLR 73

                           90
                   ....*....|....*
gi 1034611600  738 ADSPNILEEWIKVLQ 752
Cdd:cd13283     74 AESPEERQRWIDALE 88
PH_FAPP1_FAPP2 cd01247
Four phosphate adaptor protein 1 and 2 Pleckstrin homology (PH) domain; Human FAPP1 (also ...
 667-751 3.78e-08

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: 52.41  E-value: 3.78e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  667 GYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELSAsCSILRGDNKQT---VQLTTEKHtYYLTADSPNI 743
Cdd:cd01247      3 GVLWKWTNYLSGWQPRWFVLDDGVLSYYKSQEEVNQGCKGSVKMSV-CEIIVHPTDPTrmdLIIPGEQH-FYLKASSAAE 80


                   ....*...
gi 1034611600  744 LEEWIKVL 751
Cdd:cd01247     81 RQRWLVAL 88
PH_anillin cd01263
Anillin Pleckstrin homology (PH) domain; Anillin (Rhotekin/RTKN; also called PLEKHK/Pleckstrin ...
 664-755 1.12e-07

Anillin Pleckstrin homology (PH) domain; Anillin (Rhotekin/RTKN; also called PLEKHK/Pleckstrin homology domain-containing family K) is an actin binding protein involved in cytokinesis. It interacts with GTP-bound Rho proteins and results in the inhibition of their GTPase activity. Dysregulation of the Rho signal transduction pathway has been implicated in many forms of cancer. Anillin proteins have a N-terminal HRI domain/ACC (anti-parallel coiled-coil) finger domain or Rho-binding domain binds small GTPases from the Rho family. The C-terminal PH domain helps target anillin to ectopic septin containing foci. 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: 269964  Cd Length: 121  Bit Score: 51.89  E-value: 1.12e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  664 EKSGYL--LKMSGKVKSWKRRWFVLKGGELLYYKSPSDVIRK-PQGHIELSA----------------------SCSILR 718
Cdd:cd01263      3 EYRGFLtvFEDVSGLGAWHRRWCVLRGGYLSFWKYPDDEEKKkPIGSIDLTKcitekvepaprelcarpntfllETLRPA 82

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1034611600  719 GDNKQTVQLTTEKHtyYLTADSPNILEEWIKVLQNVL 755
Cdd:cd01263     83 EDDDRDDTNEKIRV--LLSADTKEERIEWLSALNQTL 117
PH_DGK_type2 cd13274
Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes ...
 665-754 2.40e-07

Type 2 Diacylglycerol kinase Pleckstrin homology (PH) domain; DGK (also called DAGK) catalyzes the conversion of diacylglycerol (DAG) to phosphatidic acid (PA) utilizing ATP as a source of the phosphate. In non-stimulated cells, DGK activity is low and DAG is used for glycerophospholipid biosynthesis. Upon receptor activation of the phosphoinositide pathway, DGK activity increases which drives the conversion of DAG to PA. DGK acts as a switch by terminating the signalling of one lipid while simultaneously activating signalling by another. There are 9 mammalian DGK isoforms all with conserved catalytic domains and two cysteine rich domains. These are further classified into 5 groups according to the presence of additional functional domains and substrate specificity: Type 1 - DGK-alpha, DGK-beta, DGK-gamma - contain EF-hand motifs and a recoverin homology domain; Type 2 - DGK-delta, DGK-eta, and DGK-kappa- contain a pleckstrin homology domain, two cysteine-rich zinc finger-like structures, and a separated catalytic region; Type 3 - DGK-epsilon - has specificity for arachidonate-containing DAG; Type 4 - DGK-zeta, DGK-iota- contain a MARCKS homology domain, ankyrin repeats, a C-terminal nuclear localization signal, and a PDZ-binding motif; Type 5 - DGK-theta - contains a third cysteine-rich domain, a pleckstrin homology domain and a proline rich region. The type 2 DGKs are present as part of this Metazoan DGK hierarchy. They have a N-terminal PH domain, two cysteine rich domains, followed by bipartite catalytic domains, and a C-terminal SAM domain. Their catalytic domains and perhaps other DGK catalytic domains may function as two independent units in a coordinated fashion. They may also require other motifs for maximal activity because several DGK catalytic domains have very little DAG kinase activity when expressed as isolated subunits. 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: 270093  Cd Length: 97  Bit Score: 50.09  E-value: 2.40e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDVIRKpqgHIELS----ASCSILRGDNkqTVQLTTEKHTYYLTADS 740
Cdd:cd13274      2 KEGPLLKQTSSFQRWKRRYFKLKGRKLYYAKDSKSLIFE---EIDLSdasvAECSTKNVNN--SFTVITPFRKLILCAES 76

                           90
                   ....*....|....
gi 1034611600  741 PNILEEWIKVLQNV 754
Cdd:cd13274     77 RKEMEEWISALKTV 90
PH_PHLDB1_2 cd14673
Pleckstrin homology-like domain-containing family B member 2 pleckstrin homology (PH) domain; ...
 667-751 3.48e-07

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: 49.88  E-value: 3.48e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  667 GYLLKMSGKVKSWKRRWFV--LKGGELLYYKSPSDviRKPQGHIELSASCSI----LRGDNKQ-----TVQLTTEKHTYY 735
Cdd:cd14673      7 GFLTKMGGKIKTWKKRWFVfdRNKRTLSYYVDKHE--KKLKGVIYFQAIEEVyydhLRSAAKSpnpalTFCVKTHDRLYY 84

                           90
                   ....*....|....*.
gi 1034611600  736 LTADSPNILEEWIKVL 751
Cdd:cd14673     85 MVAPSPEAMRIWMDVI 100
PH2_FGD5_FGD6 cd13237
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6 pleckstrin ...
 666-751 4.11e-07

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins 5 and 6 pleckstrin homology (PH) domain, C-terminus; FGD5 regulates promotes angiogenesis of vascular endothelial growth factor (VEGF) in vascular endothelial cells, including network formation, permeability, directional movement, and proliferation. The specific function of FGD6 is unknown. In general, FGDs have a RhoGEF (DH) domain, followed by a PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activate the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the PH domain is involved in intracellular targeting of the DH 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: 270057  Cd Length: 91  Bit Score: 49.33  E-value: 4.11e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  666 SGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSDVIrkPQGHIELS--ASCSILRGDNKQT---VQLTTEKHTYY-LTAD 739
Cdd:cd13237      2 SGYLQRRKKSKKSWKRLWFVLKDKVLYTYKASEDVV--ALESVPLLgfTVVTIDESFEEDEslvFQLLHKGQLPIiFRAD 79

                           90
                   ....*....|..
gi 1034611600  740 SPNILEEWIKVL 751
Cdd:cd13237     80 DAETAQRWIEAL 91
PH_Gab-like cd13324
Grb2-associated binding protein family Pleckstrin homology (PH) domain; Gab proteins are ...
 666-748 8.78e-07

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: 48.95  E-value: 8.78e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  666 SGYLLKMSGKVK----SWKRRWFVLKGGELL-------YYKspSDVIRKPQGHIEL--------SASCSILRGDNKQTVQ 726
Cdd:cd13324      4 EGWLTKSPPEKKiwraAWRRRWFVLRSGRLSggqdvleYYT--DDHCKKLKGIIDLdqceqvdaGLTFEKKKFKNQFIFD 81

                           90       100
                   ....*....|....*....|..
gi 1034611600  727 LTTEKHTYYLTADSPNILEEWI 748
Cdd:cd13324     82 IRTPKRTYYLVAETEEEMNKWV 103
PH2_Pleckstrin_2 cd13302
Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 2; Pleckstrin is a protein found in ...
 665-754 1.02e-06

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 2; 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 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: 270114  Cd Length: 109  Bit Score: 48.66  E-value: 1.02e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKVKSWKRRWFVLKG--GELLYYKSPSDviRKPQGHIELSASCSILRGDN----KQTVQ------LTTEKH 732
Cdd:cd13302      9 KQGCLLKQGHRRKNWKVRKFVLRDdpAYLHYYDPAKG--EDPLGAIHLRGCVVTAVEDNsnprKGSVEgnlfeiITADEV 86

                           90       100
                   ....*....|....*....|..
gi 1034611600  733 TYYLTADSPNILEEWIKVLQNV 754
Cdd:cd13302     87 HYYLQAATPAERTEWIKAIQMA 108
PH_ASAP cd13251
ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs ...
 663-753 1.21e-06

ArfGAP with SH3 domain, ankyrin repeat and PH domain Pleckstrin homology (PH) domain; ASAPs (ASAP1, ASAP2, and ASAP3) function as an Arf-specific GAPs, participates in rhodopsin trafficking, is associated with tumor cell metastasis, modulates phagocytosis, promotes cell proliferation, facilitates vesicle budding, Golgi exocytosis, and regulates vesicle coat assembly via a Bin/Amphiphysin/Rvs domain. ASAPs contain an NH2-terminal BAR domain, a tandem PH domain/GAP domain, three ankyrin repeats, two proline-rich regions, and a COOH-terminal Src homology 3 (SH3) 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: 270071  Cd Length: 108  Bit Score: 48.51  E-value: 1.21e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  663 LEKSGYLLKMS-GKV-KSWKRRWFVLKGGELLYYKSPSDvirKPQGHIELsASCSI-LRGDNKQTVQLTTEKHTYYLTAD 739
Cdd:cd13251     10 TEKSGYLLKKSeGKIrKVWQKRRCSIKDGFLTISHADEN---KPPAKLNL-LTCQVkLVPEDKKCFDLISHNRTYHFQAE 85

                           90
                   ....*....|....
gi 1034611600  740 SPNILEEWIKVLQN 753
Cdd:cd13251     86 DENDANAWMSVLKN 99
PH_Bud4 cd13278
Bud4 Pleckstrin homology (PH) domain; Bud4 is an anillin-like yeast protein involved in the ...
 663-755 1.23e-06

Bud4 Pleckstrin homology (PH) domain; Bud4 is an anillin-like yeast protein involved in the formation and the disassembly of the double ring structure formed by the septins during cytokinesis. Bud4 acts with Bud3 and and in parallel with septin phosphorylation by the p21-activated kinase Cla4 and the septin-dependent kinase Gin4. Bud4 is regulated by the cyclin-dependent protein kinase Cdk1, the master regulator of cell cycle progression. Bud4 contains an anillin-like domain followed by a PH domain. In addition there are two consensus Cdk phosphorylation sites: one at the N-terminus and one right before the C-terminal PH domain. Anillins also have C-terminal PH domains. 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: 241432  Cd Length: 139  Bit Score: 49.51  E-value: 1.23e-06
                           10        20        30        40        50        60        70        80
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gi 1034611600  663 LEKSGYLLKMSGKVKSWKRRWFVLKGGELLYYkspSDVIRKPQGHIELSASCSILrgDNKQTVQLTTEKHTYY------- 735
Cdd:cd13278     19 ITKEGYLLQEGGDCEYWRRRFFKLQGTKLVAY---HEVTRKPRATINLLKVVDVV--DDDDARERTSSFKRNFtdlvlfe 93

                           90       100       110
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gi 1034611600  736 --------------LTADSPNILEEWIKVLQNVL 755
Cdd:cd13278     94 ecfrlvfangevidFYADSKEEKADWYSKLKEVV 127
PH_Osh3p_yeast cd13289
Yeast oxysterol binding protein homolog 3 Pleckstrin homology (PH) domain; Yeast Osh3p is ...
 666-752 2.15e-06

Yeast oxysterol binding protein homolog 3 Pleckstrin homology (PH) domain; Yeast Osh3p is proposed to function in sterol transport and regulation of nuclear fusion during mating and of pseudohyphal growth as well as sphingolipid metabolism. Osh3 contains a N-GOLD (Golgi dynamics) domain, a PH domain, a FFAT motif (two phenylalanines in an acidic tract), and a C-terminal OSBP-related domain. GOLD domains are thought to mediate protein-protein interactions, but their role in ORPs are unknown. 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: 241443  Cd Length: 90  Bit Score: 47.25  E-value: 2.15e-06
                           10        20        30        40        50        60        70        80
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gi 1034611600  666 SGYLLKMSGK-VKSWKRRWFVL--KGGELLYYKSPSDVIRkpqGHIELSaSCSILRGDNKQTVQLTTEKHTYYLTADSPN 742
Cdd:cd13289      3 EGWLLKKRRKkMQGFARRYFVLnfKYGTLSYYFNPNSPVR---GQIPLR-LASISASPRRRTIHIDSGSEVWHLKALNDE 78

                           90
                   ....*....|
gi 1034611600  743 ILEEWIKVLQ 752
Cdd:cd13289     79 DFQAWMKALR 88
PH_ORP_plant cd13294
Plant Oxysterol binding protein related protein Pleckstrin homology (PH) domain; Plant ORPs ...
 667-752 5.80e-06

Plant Oxysterol binding protein related protein Pleckstrin homology (PH) domain; Plant ORPs contain a N-terminal PH domain and a C-terminal OSBP-related domain. Not much is known about its specific function in plants to date. Members here include: Arabidopsis, spruce, and petunia. 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: 241448  Cd Length: 100  Bit Score: 46.33  E-value: 5.80e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  667 GYLLKMSGKVKSWKRRWFVLKGGELLYYK--SPSDVirKPQGHIELS-ASCSILRGDNKQTVQLTTEKhTYYLTADSPNI 743
Cdd:cd13294      3 GILYKWVNYGKGWRSRWFVLQDGVLSYYKvhGPDKV--KPSGEVHLKvSSIRESRSDDKKFYIFTGTK-TLHLRAESRED 79


                   ....*....
gi 1034611600  744 LEEWIKVLQ 752
Cdd:cd13294     80 RAAWLEALQ 88
PRK12704 PRK12704
phosphodiesterase; Provisional
 1-92 6.01e-06

phosphodiesterase; Provisional


Pssm-ID: 237177 [Multi-domain]  Cd Length: 520  Bit Score: 50.55  E-value: 6.01e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    1 MQQLERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESETRLYNKCQDLESLIQEKDDVIQNL-ELQLEEQKQIRIQ-- 77
Cdd:PRK12704    84 LQKLEKRLLQKEENLDRKLELLEKREEELEKKEKELEQKQQELEKKEEELEELIEEQLQELERIsGLTAEEAKEILLEkv 163

                           90
                   ....*....|....*
gi 1034611600   78 EAKIIEEKAAKIKEW 92
Cdd:PRK12704   164 EEEARHEAAVLIKEI 178
FERM1_F1_Myosin-VII cd17092
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain 1, F1 sub-domain, found in Myosin-VIIa, ...
 1079-1175 6.31e-06

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain 1, F1 sub-domain, found in Myosin-VIIa, Myosin-VIIb, and similar proteins; This family includes two nontraditional members of the myosin superfamily, myosin-VIIa and myosin-VIIb. Myosin-VIIa, also termed myosin-7a (Myo7a), has been implicated in the structural organization of hair bundles at the apex of sensory hair cells (SHCs) where it serves mechanotransduction in the process of hearing and balance. Mutations in the MYO7A gene may be associated with Usher Syndrome type 1B (USH1B) and nonsyndromic hearing loss (DFNB2, DFNA11). Myosin-VIIb, also termed myosin-7b (Myo7b), is a high duty ratio motor adapted for generating and maintaining tension. It associates with harmonin and ANKS4B to form a stable ternary complex for anchoring microvilli tip-link cadherins. Like other unconventional myosins, myosin-VII is composed of a conserved motor head, a neck region and a tail region containing two MyTH4 domains, a SH3 domain, and two FERM domains. The FERM domain is made up of three sub-domains, F1, F2, and F3. The family corresponds to the F1 sub-domain of the first FERM domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N).


Pssm-ID: 340612  Cd Length: 99  Bit Score: 46.09  E-value: 6.31e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600 1079 PFSIPVHFMNGIYQVVGFDASTTVEEFLNTLNQDTGMRKpaQSGFALF---TDDPS--GRDLEHclqgnikICDIISKWE 1153
Cdd:cd17092      1 PIMLPVTFMDGSTKTVEVDSATTARELCRQLAEKLGLKD--TFGFSLYialFDKVSslGSGTDH-------VMDAISQCE 71

                           90       100
                   ....*....|....*....|..
gi 1034611600 1154 QASKEQqpGKCEGTRTVRLTYK 1175
Cdd:cd17092     72 QYAKEK--GAQEREAPWRLYFR 91
PH_Bem3 cd13277
Bud emergence protein 3 (Bem3) Pleckstrin homology (PH) domain; Bud emergence in Saccharomyces ...
 665-751 6.59e-06

Bud emergence protein 3 (Bem3) Pleckstrin homology (PH) domain; Bud emergence in Saccharomyces cerevisiae involves cell cycle-regulated reorganizations of cortical cytoskeletal elements and requires the action of the Rho-type GTPase Cdc42. Bem3 contains a RhoGAP domain and a PH domain. Though Bem3 and Bem2 both contain a RhoGAP, but only Bem3 is able to stimulate the hydrolysis of GTP on Cdc42. Bem3 is thought to be the GAP for Cdc42. 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: 270096  Cd Length: 111  Bit Score: 46.51  E-value: 6.59e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLL----KMSGKVKSWKRRWFVLKGGELLYYKSP----SDVIRKPQGHIELSASCSILRGDNKQTVQLT-------T 729
Cdd:cd13277      5 KEGYLLkrrkKTLGSTGGWKLRYGVLDGNILELYESRggqlLESIKLRNAQIERQPNLPDDKYGTRHGFLINehkksglS 84

                           90       100
                   ....*....|....*....|..
gi 1034611600  730 EKHTYYLTADSPNILEEWIKVL 751
Cdd:cd13277     85 STTKYYLCAETDKERDEWVSAL 106
PH_ORP9 cd13290
Human Oxysterol binding protein related protein 9 Pleckstrin homology (PH) domain; Human ORP9 ...
 667-756 7.23e-06

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: 46.28  E-value: 7.23e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  667 GYLLKMSGKVKSWKRRWFVL--KGGELLYYKSPSDVIRKPQ-GHIELSASCSILRGDNKQTVQLTTEKHTYYLTADSPNI 743
Cdd:cd13290      3 GPLSKWTNVMKGWQYRWFVLddNAGLLSYYTSKEKMMRGSRrGCVRLKGAVVGIDDEDDSTFTITVDQKTFHFQARDAEE 82

                           90
                   ....*....|...
gi 1034611600  744 LEEWIKVLQNVLR 756
Cdd:cd13290     83 RERWIRALEDTIL 95
PH_Btk cd01238
Bruton's tyrosine kinase pleckstrin homology (PH) domain; Btk is a member of the Tec family of ...
 665-757 9.64e-06

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


Pssm-ID: 269944 [Multi-domain]  Cd Length: 140  Bit Score: 46.84  E-value: 9.64e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMS-GKVK----SWKRRWFVLKGGELLYYKSPSDVIRKPQGHIELS-----------ASCsilrgDNKQTVQLT 728
Cdd:cd01238      1 LEGLLVKRSqGKKRfgpvNYKERWFVLTKSSLSYYEGDGEKRGKEKGSIDLSkvrcveevkdeAFF-----ERKYPFQVV 75

                           90       100
                   ....*....|....*....|....*....
gi 1034611600  729 TEKHTYYLTADSPNILEEWIKVLQNVLRV 757
Cdd:cd01238     76 YDDYTLYVFAPSEEDRDEWIAALRKVCRN 104
PH_11 pfam15413
Pleckstrin homology domain; This Pleckstrin homology domain is found in some fungal species.
 665-752 1.47e-05

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


Pssm-ID: 405988  Cd Length: 105  Bit Score: 45.27  E-value: 1.47e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKvkSWKRRWF-VLKGGELLYYKSPSDVIRKPQGHIELSASC----SILRGDNkQTVQ------------- 726
Cdd:pfam15413    1 IEGYLKKKGPK--TWKHRWFaVLRNGVLFYYKSEKMKVVKHVIVLSNYIVGklgtDIISGAL-FKIDnirsetsddllle 77

                           90       100
                   ....*....|....*....|....*.
gi 1034611600  727 LTTEKHTYYLTADSPNILEEWIKVLQ 752
Cdd:pfam15413   78 ISTETKIFFLYGDNNEETYEWVEALQ 103
PH_Gab2_2 cd13384
Grb2-associated binding protein family pleckstrin homology (PH) domain; The Gab subfamily ...
 679-748 1.48e-05

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: 45.51  E-value: 1.48e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  679 WKRRWFVLKGGE------LLYYKspSDVIRKPQGHIELSaSC----SILRGDNKQTVQ------LTTEKHTYYLTADSPN 742
Cdd:cd13384     23 WRRRYFVLRQSEipgqyfLEYYT--DRTCRKLKGSIDLD-QCeqvdAGLTFETKNKLKdqhifdIRTPKRTYYLVADTED 99


                   ....*.
gi 1034611600  743 ILEEWI 748
Cdd:cd13384    100 EMNKWV 105
PH_3 pfam14593
PH domain;
659-756 1.90e-05

PH domain;


Pssm-ID: 434057  Cd Length: 103  Bit Score: 44.92  E-value: 1.90e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  659 KNEPLEKSGYLLKMSGKVKswKRRWFVLKGGELLYYKSPSDVIRKpqGHIELSASCSIlRGDNKQTVQLTTEKHTYYLTa 738
Cdd:pfam14593    9 PGELILKQGLVKKRKGLFA--KKRQLILTDGPRLIYVDPVKMVLK--GEIPWSKELKV-EAKNFKTFFIHTPNRTYYLE- 82

                           90
                   ....*....|....*...
gi 1034611600  739 DSPNILEEWIKVLQNVLR 756
Cdd:pfam14593   83 DPEGDALKWCKAIEDVRK 100
PH_Skap_family cd13266
Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor ...
 665-757 2.29e-05

Src kinase-associated phosphoprotein family Pleckstrin homology (PH) domain; Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Src kinase-associated phosphoprotein of 55 kDa (Skap55)/Src kinase-associated phosphoprotein 1 (Skap1), Skap2, and Skap-homology (Skap-hom) have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. 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: 270086  Cd Length: 106  Bit Score: 44.82  E-value: 2.29e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGK----VKSWKRRWFVLKGGELLYYKSPSDviRKPQGHIELSA----SCSILRGDNKQ--TVQLTT-EKHT 733
Cdd:cd13266      3 KAGYLEKRRKDhsffGSEWQKRWCAISKNVFYYYGSDKD--KQQKGEFAINGydvrMNPTLRKDGKKdcCFELVCpDKRT 80

                           90       100
                   ....*....|....*....|....
gi 1034611600  734 YYLTADSPNILEEWIKVLQNVLRV 757
Cdd:cd13266     81 YQFTAASPEDAEDWVDQISFILQD 104
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 771-873 2.29e-05

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: 44.85  E-value: 2.29e-05
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600   771 PTMKGLLTKVKHGYS---KRVWCTLIGKTLYYFRS---QEDKFPLGQIKLWEAKVEEVDRSCDSDEDyeasgrsllsthY 844
Cdd:smart00233    1 VIKEGWLYKKSGGGKkswKKRYFVLFNSTLLYYKSkkdKKSYKPKGSIDLSGCTVREAPDPDSSKKP------------H 68

                            90       100
                    ....*....|....*....|....*....
gi 1034611600   845 TIVIHPKDQGPTYLLIGSKHEKDTWLYHL 873
Cdd:smart00233   69 CFEIKTSDRKTLLLQAESEEEREKWVEAL 97
PH2_FGD1-4 cd13236
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins pleckstrin homology (PH) ...
 670-751 2.94e-05

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia proteins pleckstrin homology (PH) domain, C-terminus; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. Not much is known about FGD2. FGD1 is the best characterized member of the group with mutations here leading to the X-linked disorder known as faciogenital dysplasia (FGDY). Both FGD1 and FGD3 are targeted by the ubiquitin ligase SCF(FWD1/beta-TrCP) upon phosphorylation of two serine residues in its DSGIDS motif and subsequently degraded by the proteasome. However, FGD1 and FGD3 induced significantly different morphological changes in HeLa Tet-Off cells and while FGD1 induced long finger-like protrusions, FGD3 induced broad sheet-like protrusions when the level of GTP-bound Cdc42 was significantly increased by the inducible expression of FGD3. They also reciprocally regulated cell motility in inducibly expressed in HeLa Tet-Off cells, FGD1 stimulated cell migration while FGD3 inhibited it. FGD1 and FGD3 therefore play different roles to regulate cellular functions, even though their intracellular levels are tightly controlled by the same destruction pathway through SCF(FWD1/beta-TrCP). FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. 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: 270056  Cd Length: 105  Bit Score: 44.26  E-value: 2.94e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  670 LKMSGKVKSWKRRWFVLKGGE--LLY-YKSPSDVirKPQGHI-----ELSASCSILRGDNKQTVQLTTEKHTYYLTADSP 741
Cdd:cd13236     14 LQYSEKGKTWQKVWCVIPRTEplVLYlYGAPQDV--RAQRTIplpgcEVTVPPPEERLDGRHVFKLSQSKQSHYFSAESE 91

                           90
                   ....*....|
gi 1034611600  742 NILEEWIKVL 751
Cdd:cd13236     92 ELQQRWLEAL 101
PH_KIFIA_KIFIB cd01233
KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA ...
 659-751 2.95e-05

KIFIA and KIFIB protein pleckstrin homology (PH) domain; The kinesin-3 family motors KIFIA (Caenorhabditis elegans homolog unc-104) and KIFIB transport synaptic vesicle precursors that contain synaptic vesicle proteins, such as synaptophysin, synaptotagmin and the small GTPase RAB3A, but they do not transport organelles that contain plasma membrane proteins. They have a N-terminal motor domain, followed by a coiled-coil domain, and a C-terminal PH domain. KIF1A adopts a monomeric form in vitro, but acts as a processive dimer in vivo. KIF1B has alternatively spliced isoforms distinguished by the presence or absence of insertion sequences in the conserved amino-terminal region of the protein; this results in their different motor activities. KIF1A and KIF1B bind to RAB3 proteins through the adaptor protein mitogen-activated protein kinase (MAPK) -activating death domain (MADD; also calledDENN), which was first identified as a RAB3 guanine nucleotide exchange factor (GEF). 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: 269939  Cd Length: 103  Bit Score: 44.51  E-value: 2.95e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  659 KNEPLEKSGYLLKMSGKVKSWKRRWFVLKGGELLYYKSPSD-----VIRKPQGHIELSASCSILRGdNKQTVQLTTEKHT 733
Cdd:cd01233      2 KSPVVSKRGYLLFLEDATDGWVRRWVVLRRPYLHIYSSEKDgdergVINLSTARVEYSPDQEALLG-RPNVFAVYTPTNS 80

                           90
                   ....*....|....*...
gi 1034611600  734 YYLTADSPNILEEWIKVL 751
Cdd:cd01233     81 YLLQARSEKEMQDWLYAI 98
PH_GAP1-like cd01244
RAS p21 protein activator (GTPase activating protein) family pleckstrin homology (PH) domain; ...
 665-756 3.06e-05

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: 44.59  E-value: 3.06e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLK--MSGK----VKSWKRRWFVLKGGELLYYKSPSDvirKPQGHIELSASCSILRGDN-----KQTVQLTTEKHT 733
Cdd:cd01244      1 KEGYLIKraQGRKkkfgRKNFKKRYFRLTNEALSYSKSKGK---QPLCSIPLEDILAVERVEEesfkmKNMFQIVQPDRT 77

                           90       100
                   ....*....|....*....|...
gi 1034611600  734 YYLTADSPNILEEWIKVLQNVLR 756
Cdd:cd01244     78 LYLQAKNVVELNEWLSALRKVCL 100
PH_PLEKHD1 cd13281
Pleckstrin homology (PH) domain containing, family D (with coiled-coil domains) member 1 PH ...
 664-757 3.20e-05

Pleckstrin homology (PH) domain containing, family D (with coiled-coil domains) member 1 PH domain; Human PLEKHD1 (also called UPF0639, pleckstrin homology domain containing, family D (with M protein repeats) member 1) is a single transcript and contains a single PH domain. PLEKHD1 is conserved in human, chimpanzee, , dog, cow, mouse, chicken, zebrafish, and Caenorhabditis elegans. 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: 270099  Cd Length: 139  Bit Score: 45.39  E-value: 3.20e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  664 EKSGYLLK--MSGKVKSWKRRWFVLKGGELLYYkspSDVIRK-----------PQGHIELsASCSILRG-DNKQTVQLTT 729
Cdd:cd13281     13 QLHGILWKkpFGHQSAKWSKRFFIIKEGFLLYY---SESEKKdfektrhfnihPKGVIPL-GGCSIEAVeDPGKPYAISI 88

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1034611600  730 EkHTYY-----LTADSPNILEEWIKVLQNVLRV 757
Cdd:cd13281     89 S-HSDFkgniiLAADSEFEQEKWLDMLRESGKI 120
SMC_prok_A TIGR02169
chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of ...
 1-145 3.23e-05

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274009 [Multi-domain]  Cd Length: 1164  Bit Score: 48.53  E-value: 3.23e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    1 MQQLERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESETRLYN---KCQDLESLIQEKDDVIQNLELQLEEQKQ-IRI 76
Cdd:TIGR02169  711 LSDASRKIGEIEKEIEQLEQEEEKLKERLEELEEDLSSLEQEIENvksELKELEARIEELEEDLHKLEEALNDLEArLSH 790

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034611600   77 QEAKIIEEKAAKIKEWVT---VKLNELELENQNLRLINQNQTEEIRTMQSKLQEVQGKKSSTVSTLKLSEGQ 145
Cdd:TIGR02169  791 SRIPEIQAELSKLEEEVSrieARLREIEQKLNRLTLEKEYLEKEIQELQEQRIDLKEQIKSIEKEIENLNGK 862
PH_Gab1_Gab2 cd01266
Grb2-associated binding proteins 1 and 2 pleckstrin homology (PH) domain; The Gab subfamily ...
 666-762 4.16e-05

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: 44.55  E-value: 4.16e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  666 SGYLLKMSGKVK----SWKRRWFVLKGGELL-------YYKspSDVIRKPQGHIELSASCSILRG--DNKQTVQ------ 726
Cdd:cd01266      7 SGWLRKSPPEKKlrryAWKKRWFVLRSGRLSgdpdvleYYK--NDHAKKPIRVIDLNLCEQVDAGltFNKKELEnsyifd 84

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1034611600  727 LTTEKHTYYLTADSPNILEEWIKvlqNVLRVQAANP 762
Cdd:cd01266     85 IKTIDRIFYLVAETEEDMNKWVR---NICDICGFNP 117
PH_Skap-hom_Skap2 cd13381
Src kinase-associated phosphoprotein homolog and Skap 2 Pleckstrin homology (PH) domain; ...
 665-756 4.69e-05

Src kinase-associated phosphoprotein homolog and Skap 2 Pleckstrin homology (PH) domain; Adaptor protein Skap-hom, a homolog of Skap55, which interacts with actin and with ADAP (adhesion and degranulation promoting adapter protein) undergoes tyrosine phosphorylation in response to plating of bone marrow-derived macrophages on fibronectin. Skap-hom has an N-terminal coiled-coil conformation that is involved in homodimer formation, a central PH domain and a C-terminal SH3 domain that associates with ADAP. The Skap-hom PH domain regulates intracellular targeting; its interaction with the DM domain inhibits Skap-hom actin-based ruffles in macrophages and its binding to 3'-phosphoinositides reverses this autoinhibition. The Skap-hom PH domain binds PI[3,4]P2 and PI[3,4,5]P3, but not to PI[3]P, PI[5]P, or PI[4,5]P2. Skap2 is a downstream target of Heat shock transcription factor 4 (HSF4) and functions in the regulation of actin reorganization during lens differentiation. It is thought that SKAP2 anchors the complex of tyrosine kinase adaptor protein 2 (NCK20/focal adhesion to fibroblast growth factor receptors at the lamellipodium in lens epithelial cells. Skap2 has an N-terminal coiled-coil conformation which interacts with the SH2 domain of NCK2, a central PH domain and a C-terminal SH3 domain that associates with ADAP (adhesion and degranulation promoting adapter protein)/FYB (the Fyn binding protein). Skap2 PH domain binds to membrane lipids. Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Src kinase-associated phosphoprotein of 55 kDa (Skap55)/Src kinase-associated phosphoprotein 1 (Skap1), Skap2, and Skap-hom have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. 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: 270181  Cd Length: 106  Bit Score: 43.79  E-value: 4.69e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKM----SGKVKSWKRRWFVLKGGELLYYKSPSDVIRKPQGHIE--LSASCSILRGDNKQTV---QLTTEKHTYY 735
Cdd:cd13381      3 KAGYLEKRrkdhSFFGFEWQKRWCALSNSVFYYYGSDKDKQQKGEFAIDgyDVKMNNTLRKDAKKDCcfeICAPDKRVYQ 82

                           90       100
                   ....*....|....*....|.
gi 1034611600  736 LTADSPNILEEWIKVLQNVLR 756
Cdd:cd13381     83 FTAASPKEAEEWVQQIKFILQ 103
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
 1-131 6.91e-05

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 47.74  E-value: 6.91e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    1 MQQLERQVidaeRQAEKAFQQVQVMEDKLKAANIQTSESETRLYNKCQDLESLIQEKDDVIQNLELQLEEQKQIRIQEAK 80
Cdd:TIGR02168  784 IEELEAQI----EQLKEELKALREALDELRAELTLLNEEAANLRERLESLERRIAATERRLEDLEEQIEELSEDIESLAA 859

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034611600   81 IIEE---KAAKIKEWVTVKLNELELENQNLRLIN---QNQTEEIRTMQSKLQEVQGK 131
Cdd:TIGR02168  860 EIEEleeLIEELESELEALLNERASLEEALALLRselEELSEELRELESKRSELRRE 916
PH_CNK_mammalian-like cd01260
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
 679-751 7.39e-05

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: 43.55  E-value: 7.39e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034611600  679 WKRRWFVLKGGELLYYKSPSDviRKPQGHIELSaSCSILRGDN---KQTVQLTTEK-HTYYLTADSPNILEEWIKVL 751
Cdd:cd01260     33 WKKYWFVLKGSSLYWYSNQQD--EKAEGFINLP-DFKIERASEckkKYAFKACHPKiKTFYFAAENLDDMNKWLSKL 106
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
1-129 8.69e-05

Uncharacterized protein, contains DUF3084 domain [Function unknown];


Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 46.43  E-value: 8.69e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    1 MQQLERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESETRLYNKCQDLESLIQEKDDVIQNLELQLEEQKQIRIQEAK 80
Cdd:COG4372     61 LEQLEEELEQARSELEQLEEELEELNEQLQAAQAELAQAQEELESLQEEAEELQEELEELQKERQDLEQQRKQLEAQIAE 140

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1034611600   81 IIEEKAAKIKEwvtvkLNELE-----LENQNLRLINQNQTEEIRTMQSKLQEVQ 129
Cdd:COG4372    141 LQSEIAEREEE-----LKELEeqlesLQEELAALEQELQALSEAEAEQALDELL 189
Smc COG1196
Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...
 1-147 9.09e-05

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 440809 [Multi-domain]  Cd Length: 983  Bit Score: 47.24  E-value: 9.09e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    1 MQQLERQVIDAERQAEKA--FQQVQVMEDKLKA------------------ANIQTSESE-TRLYNKCQDLESLIQEKDD 59
Cdd:COG1196    195 LGELERQLEPLERQAEKAerYRELKEELKELEAellllklreleaeleeleAELEELEAElEELEAELAELEAELEELRL 274

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600   60 VIQNLELQLEE-QKQIRIQEAKIIEEKAAKIKEW-----VTVKLNELELENQNLRLINQNQTEEIRTMQSKLQEVQGKKS 133
Cdd:COG1196    275 ELEELELELEEaQAEEYELLAELARLEQDIARLEerrreLEERLEELEEELAELEEELEELEEELEELEEELEEAEEELE 354

                          170
                   ....*....|....
gi 1034611600  134 STVSTLKLSEGQRL 147
Cdd:COG1196    355 EAEAELAEAEEALL 368
PH_Ses cd13288
Sesquipedalian family Pleckstrin homology (PH) domain; The sesquipedalian family has 2 ...
 770-832 1.20e-04

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: 43.00  E-value: 1.20e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1034611600  770 KPTMKGLLTK---VKHGYSKRvWCTLIGKTLYYFRSQEDKFPLGQIKLWEAKVEevdrSCDSDEDY 832
Cdd:cd13288      7 PVDKEGYLWKkgeRNTSYQKR-WFVLKGNLLFYFEKKGDREPLGVIVLEGCTVE----LAEDAEPY 67
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
 1-150 1.64e-04

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 46.59  E-value: 1.64e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    1 MQQLERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESETR----------LYNKCQDLESLIQEKDDVIQNLELQLEE 70
Cdd:TIGR02168  241 LEELQEELKEAEEELEELTAELQELEEKLEELRLEVSELEEEieelqkelyaLANEISRLEQQKQILRERLANLERQLEE 320

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600   71 -QKQIRIQEAKIIE--EKAAKIKEWVTV----------KLNELELENQNLRLINQNQTEEIRTMQSKLQEVQGKKSSTVS 137
Cdd:TIGR02168  321 lEAQLEELESKLDElaEELAELEEKLEElkeelesleaELEELEAELEELESRLEELEEQLETLRSKVAQLELQIASLNN 400

                          170
                   ....*....|...
gi 1034611600  138 TLKLSEgQRLSSL 150
Cdd:TIGR02168  401 EIERLE-ARLERL 412
PH_DOCK-D cd13267
Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also ...
 659-755 1.87e-04

Dedicator of cytokinesis-D subfamily Pleckstrin homology (PH) domain; DOCK-D subfamily (also called Zizimin subfamily) consists of Dock9/Zizimin1, Dock10/Zizimin3, and Dock11/Zizimin2. DOCK-D has a N-terminal DUF3398 domain, a PH-like domain, a Dock Homology Region 1, DHR1 (also called CZH1), a C2 domain, and a C-terminal DHR2 domain (also called CZH2). Zizimin1 is enriched in the brain, lung, and kidney; zizimin2 is found in B and T lymphocytes, and zizimin3 is enriched in brain, lung, spleen and thymus. Zizimin1 functions in autoinhibition and membrane targeting. Zizimin2 is an immune-related and age-regulated guanine nucleotide exchange factor, which facilitates filopodial formation through activation of Cdc42, which results in activation of cell migration. No function has been determined for Zizimin3 to date. The N-terminal half of zizimin1 binds to the GEF domain through three distinct areas, including CZH1, to inhibit the interaction with Cdc42. In addition its PH domain binds phosphoinositides and mediates zizimin1 membrane targeting. DOCK is a family of proteins involved in intracellular signalling networks. They act as guanine nucleotide exchange factors for small G proteins of the Rho family, such as Rac and Cdc42. There are 4 subfamilies of DOCK family proteins based on their sequence homology: A-D. 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: 270087  Cd Length: 126  Bit Score: 42.70  E-value: 1.87e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  659 KNEPLEKSGYLLK--MSGK-------VKSWKRRWFVLKGGE-----LLYYKSpsDVIRKPQGHIELSaSCSILRGDNKQ- 723
Cdd:cd13267      2 GESGITKEGYLYKgpENSSdsfislaMKSFKRRFFHLKQLVdgsyiLEFYKD--EKKKEAKGTIFLD-SCTGVVQNSKRr 78

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1034611600  724 --TVQL-TTEKHTYYLTADSPNILEEWIKVLQNVL 755
Cdd:cd13267     79 kfCFELrMQDKKSYVLAAESEAEMDEWISKLNKIL 113
PH2_FGD4_insect-like cd13238
FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 4 pleckstrin homology (PH) ...
 666-751 1.99e-04

FYVE, RhoGEF and PH domain containing/faciogenital dysplasia protein 4 pleckstrin homology (PH) domain, C-terminus, in insect and related arthropods; In general, FGDs have a RhoGEF (DH) domain, followed by an N-terminal PH domain, a FYVE domain and a C-terminal PH domain. All FGDs are guanine nucleotide exchange factors that activates the Rho GTPase Cdc42, an important regulator of membrane trafficking. The RhoGEF domain is responsible for GEF catalytic activity, while the N-terminal PH domain is involved in intracellular targeting of the DH domain. FGD4 is one of the genes associated with Charcot-Marie-Tooth neuropathy type 4 (CMT4), a group of progressive motor and sensory axonal and demyelinating neuropathies that are distinguished from other forms of CMT by autosomal recessive inheritance. Those affected have distal muscle weakness and atrophy associated with sensory loss and, frequently, pes cavus foot deformity. This cd contains insects, crustaceans, and chelicerates. 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: 270058  Cd Length: 97  Bit Score: 41.86  E-value: 1.99e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  666 SGYLLKMSGKVKSWKRRWFVLKGGELLY-YKSPSDVIRKPQGHI------ELSASCSILRGDNKQ---TVQLTTEKHTYY 735
Cdd:cd13238      2 SGYLKLKTNGRKTWSRRWFALQPDFVLYsYKSQEDKLPLTATPVpgflvtLLEKGSAVDPLNDPKrprTFKMFHVKKSYY 81

                           90
                   ....*....|....*.
gi 1034611600  736 LTADSPNILEEWIKVL 751
Cdd:cd13238     82 FQANDGDEQKKWVLTL 97
Niban-like cd23949
Niban-like protein; Niban-like proteins contain an N-terminal Pleckstrin-Homology (PH) domain ...
 663-756 2.00e-04

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: 45.75  E-value: 2.00e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  663 LEKSGYLLKMSGKVKSWKRRWFVLKG-GELLYYKSPSDVIR--KPQGHIELS----------------ASCSILRGDNKQ 723
Cdd:cd23949     62 VIFSGKLSKYGEDSKKWKERFCVVRGdYNLEYYESKEAYERgkKPKGSINLAgykvltspeeylelvdRKFPDLAGKSEK 141

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1034611600  724 TVQLTTEKHT-------------YYLTADSPNILEEWIKVLQNVLR 756
Cdd:cd23949    142 ASVPFPERPPpftlelyhpyrrhYYFCFETEKEQEEWVAVLQDCIR 187
PH_RIP cd01236
Rho-Interacting Protein Pleckstrin homology (PH) domain; RIP1-RhoGDI2 was obtained in a screen ...
 677-752 2.03e-04

Rho-Interacting Protein Pleckstrin homology (PH) domain; RIP1-RhoGDI2 was obtained in a screen for proteins that bind to wild-type RhoA. RIP2, RIP3, and RIP4 were isolated from cDNA libraries with constitutively active V14RhoA (containing the C190R mutation). RIP2 represents a novel GDP/GTP exchange factor (RhoGEF), while RIP3 (p116Rip) and RIP4 are thought to be structural proteins. RhoGEF contains a Dbl(DH)/PH region, a a zinc finger motif, a leucine-rich domain, and a coiled-coil region. The last 2 domains are thought to be involved in mediating protein-protein interactions. RIP3 is a negative regulator of RhoA signaling that inhibits, either directly or indirectly, RhoA-stimulated actomyosin contractility. In plants RIP3 is localized at microtubules and interacts with the kinesin-13 family member AtKinesin-13A, suggesting a role for RIP3 in microtubule reorganization and a possible function in Rho proteins of plants (ROP)-regulated polar growth. It has a PH domain, two proline-rich regions which are putative binding sites for SH3 domains, and a COOH-terminal coiled-coil region which overlaps with the RhoA-binding region. 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: 269942  Cd Length: 136  Bit Score: 42.81  E-value: 2.03e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  677 KSWKRRWFVL-KGGELLYY--KSPSDVirkPQGHIELSASCSILRGD----NKQTVQLTTEKHTYYLTADSPNILEEWIK 749
Cdd:cd01236     52 KRWQRRWFVLyDDGELTYAldEMPDTL---PQGSIDMSQCTEVTDAEartgHPHSLAITTPERIHFVKADSKEEIRWWLE 128


                   ...
gi 1034611600  750 VLQ 752
Cdd:cd01236    129 LLA 131
Myosin_tail_1 pfam01576
Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and ...
 2-140 3.07e-04

Myosin tail; The myosin molecule is a multi-subunit complex made up of two heavy chains and four light chains it is a fundamental contractile protein found in all eukaryote cell types. This family consists of the coiled-coil myosin heavy chain tail region. The coiled-coil is composed of the tail from two molecules of myosin. These can then assemble into the macromolecular thick filament. The coiled-coil region provides the structural backbone the thick filament.


Pssm-ID: 460256 [Multi-domain]  Cd Length: 1081  Bit Score: 45.55  E-value: 3.07e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    2 QQLERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESE---TRLYNKCQDLEsliqekdDVIQNLELQLEE-------- 70
Cdd:pfam01576   22 QKAESELKELEKKHQQLCEEKNALQEQLQAETELCAEAEemrARLAARKQELE-------EILHELESRLEEeeersqql 94

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600   71 -------QKQIRIQEAKIIEEKAAKIK---EWVTV--KLNELE-----LENQNLRLINQNQ--TEEIRTMQSKLQEvQGK 131
Cdd:pfam01576   95 qnekkkmQQHIQDLEEQLDEEEAARQKlqlEKVTTeaKIKKLEedillLEDQNSKLSKERKllEERISEFTSNLAE-EEE 173


                   ....*....
gi 1034611600  132 KSSTVSTLK 140
Cdd:pfam01576  174 KAKSLSKLK 182
PH_OPR5_ORP8 cd13286
Human Oxysterol binding protein related proteins 5 and 8 Pleckstrin homology (PH) domain; ...
 670-697 3.19e-04

Human Oxysterol binding protein related proteins 5 and 8 Pleckstrin homology (PH) domain; Human ORP5 is proposed to function in efficient nonvesicular transfer of low-density lipoproteins-derived cholesterol (LDL-C) from late endosomes/lysosomes to the endoplasmic reticulum (ER). Human ORP8 is proposed to modulate lipid homeostasis and sterol regulatory element binding proteins (SREBP) activity. Both ORP5 and ORP8 contain a N-terminal PH domain, a C-terminal OSBP-related domain, followed by a transmembrane domain that localizes ORP5 to the ER. Unlike all the other human OSBP/ORPs they lack a FFAT motif (two phenylalanines in an acidic tract). 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: 270103  Cd Length: 130  Bit Score: 42.34  E-value: 3.19e-04
                           10        20
                   ....*....|....*....|....*...
gi 1034611600  670 LKMSGKVKSWKRRWFVLKGGELLYYKSP 697
Cdd:cd13286     14 LKIRGTLKSWTKLWCVLKPGVLLLYKSP 41
EnvC COG4942
Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, ...
 1-134 4.21e-04

Septal ring factor EnvC, activator of murein hydrolases AmiA and AmiB [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 443969 [Multi-domain]  Cd Length: 377  Bit Score: 44.37  E-value: 4.21e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    1 MQQLERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESETRLYNKCQDLESLIQEkddvIQNLELQLEEQKQIRIQEAK 80
Cdd:COG4942     36 IAELEKELAALKKEEKALLKQLAALERRIAALARRIRALEQELAALEAELAELEKE----IAELRAELEAQKEELAELLR 111

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034611600   81 iieeKAAKIKEWVTVKL-------NELELENQNLRLINQNQTEEIRTMQSKLQEVQGKKSS 134
Cdd:COG4942    112 ----ALYRLGRQPPLALllspedfLDAVRRLQYLKYLAPARREQAEELRADLAELAALRAE 168
Smc COG1196
Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...
 2-129 4.54e-04

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 440809 [Multi-domain]  Cd Length: 983  Bit Score: 44.93  E-value: 4.54e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    2 QQLERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESETRLYNKCQDLESLIQEKDDVIQNLELQLEEQKQIRIQEAKI 81
Cdd:COG1196    256 EELEAELAELEAELEELRLELEELELELEEAQAEEYELLAELARLEQDIARLEERRRELEERLEELEEELAELEEELEEL 335

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1034611600   82 IEEKAAKIKEwVTVKLNELELENQNLRLINQNQTEEIRTMQSKLQEVQ 129
Cdd:COG1196    336 EEELEELEEE-LEEAEEELEEAEAELAEAEEALLEAEAELAEAEEELE 382
Smc COG1196
Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning]; ...
 1-129 4.65e-04

Chromosome segregation ATPase Smc [Cell cycle control, cell division, chromosome partitioning];


Pssm-ID: 440809 [Multi-domain]  Cd Length: 983  Bit Score: 44.93  E-value: 4.65e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    1 MQQLERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESETRLYNKCQDLESLIQEKDDVIQNLELQLEEQKQIRIQEAK 80
Cdd:COG1196    286 AQAEEYELLAELARLEQDIARLEERRRELEERLEELEEELAELEEELEELEEELEELEEELEEAEEELEEAEAELAEAEE 365

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1034611600   81 IIEEKAAKIKEWVTVKLNELELENQNLRLINQNQTEEIRTMQSKLQEVQ 129
Cdd:COG1196    366 ALLEAEAELAEAEEELEELAEELLEALRAAAELAAQLEELEEAEEALLE 414
PH_ORP10_ORP11 cd13291
Human Oxysterol binding protein (OSBP) related proteins 10 and 11 (ORP10 and ORP11) Pleckstrin ...
 667-711 4.68e-04

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: 41.13  E-value: 4.68e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*..
gi 1034611600  667 GYLLKMSGKVKSWKRRWFVL--KGGELLYYKSPSDVIRKPQGHIELS 711
Cdd:cd13291      3 GQLLKYTNVVKGWQNRWFVLdpDTGILEYFLSEESKNQKPRGSLSLA 49
FERM_F1_Myo10_like cd17110
FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in unconventional ...
 1097-1180 4.68e-04

FERM (Four.1 protein, Ezrin, Radixin, Moesin) domain, F1 sub-domain, found in unconventional myosin-X and similar proteins; Myosin-X, also termed myosin-10 (Myo10), is an untraditional member of myosin superfamily. It is an actin-based motor protein that plays a critical role in diverse cellular motile events, such as filopodia formation/extension, phagocytosis, cell migration, and mitotic spindle maintenance, as well as a number of disease states including cancer metastasis and pathogen infection. Myosin-X functions as an important regulator of cytoskeleton that modulates cell motilities in many different cellular contexts. It regulates neuronal radial migration through interacting with N-cadherin. Like other unconventional myosins, Myosin-X is composed of a conserved motor head, a neck region and a variable tail. The neck region consists of three IQ motifs (light chain-binding sites), and a predicted stalk of coiled coil. The tail contains three PEST regions, three PH domains, a MyTH4 domain, and a FERM domain. The FERM domain is made up of three sub-domains, F1, F2, and F3. This family corresponds to the F1 sub-domain, which is also called the N-terminal ubiquitin-like structural domain of the FERM domain (FERM_N). Amoebozoan Dictyostelium discoideum myosin VII (DdMyo7) and uncharacterized pleckstrin homology domain-containing family H member 3 (PLEKHH3) are also included in this family. Like metazoan Myo10, DdMyo7 is essential for the extension of filopodia, plasma membrane protrusions filled with parallel bundles of F-actin.


Pssm-ID: 340630  Cd Length: 97  Bit Score: 40.83  E-value: 4.68e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600 1097 DASTTVEEFLNTLNQDTGMRKpAQSGFALFtdDPSGrDLEHCLQGNIKICDIISKWEqasKEQQPGKCEGTRTVRLTYKN 1176
Cdd:cd17110     21 DSWTTCGEVSKDLARRLGLER-SRNGFALF--ETSG-DIERALEAKTRVVDVLSKWE---KLAATGSSPGDDGWKLLFKL 93


                   ....
gi 1034611600 1177 RLYF 1180
Cdd:cd17110     94 YLFL 97
PH_rhotekin2 cd13249
Anillin Pleckstrin homology (PH) domain; Anillin (Rhotekin/RTKN; also called PLEKHK/Pleckstrin ...
 666-751 4.99e-04

Anillin Pleckstrin homology (PH) domain; Anillin (Rhotekin/RTKN; also called PLEKHK/Pleckstrin homology domain-containing family K) is an actin binding protein involved in cytokinesis. It interacts with GTP-bound Rho proteins and results in the inhibition of their GTPase activity. Dysregulation of the Rho signal transduction pathway has been implicated in many forms of cancer. Anillin proteins have a N-terminal HRI domain/ACC (anti-parallel coiled-coil) finger domain or Rho-binding domain binds small GTPases from the Rho family. The C-terminal PH domain helps target anillin to ectopic septin containing foci. 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: 270069  Cd Length: 111  Bit Score: 41.21  E-value: 4.99e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  666 SGYL--LKMSGKVKSWKRRWFVLKGGELLYYKSPSDVIRK--PQGHIELSASCSILRGDN-----KQTVQLTT----EKH 732
Cdd:cd13249      5 SGYLsqQQSVEGLQSWTRLYCVLKGGNLLCYYSPEEIEAKvePLLTIPINKETRIRAVEKdskgrASSLSIINpysgEEV 84

                           90
                   ....*....|....*....
gi 1034611600  733 TYYLTADSPNILEEWIKVL 751
Cdd:cd13249     85 THVLSADSREELQKWMEAL 103
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
1-131 5.07e-04

Uncharacterized protein, contains DUF3084 domain [Function unknown];


Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 44.12  E-value: 5.07e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    1 MQQLERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESETRLYNKCQDLESLIQEKDDVIQNLELQLEEQKQIRIQEAK 80
Cdd:COG4372     54 LEQAREELEQLEEELEQARSELEQLEEELEELNEQLQAAQAELAQAQEELESLQEEAEELQEELEELQKERQDLEQQRKQ 133

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1034611600   81 iIEEKAAKIKEWVTVKLNEL-ELENQNLRLINQNQTEEIRTMQSKLQEVQGK 131
Cdd:COG4372    134 -LEAQIAELQSEIAEREEELkELEEQLESLQEELAALEQELQALSEAEAEQA 184
SMC_prok_A TIGR02169
chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of ...
 3-140 5.07e-04

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274009 [Multi-domain]  Cd Length: 1164  Bit Score: 44.67  E-value: 5.07e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    3 QLERQVIDAERQ-AEKAFQQVQVMEDKLKA------ANIQTSESET-RLYNKCQDLESLIQEKDDVIQNLELQLEEQKQi 74
Cdd:TIGR02169  776 KLEEALNDLEARlSHSRIPEIQAELSKLEEevsrieARLREIEQKLnRLTLEKEYLEKEIQELQEQRIDLKEQIKSIEK- 854

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600   75 RIQEAKI-IEEKAAKIKEwVTVKLNELELENQNLRLINQNQTEEIRTMQSKLQEVQG---KKSSTVSTLK 140
Cdd:TIGR02169  855 EIENLNGkKEELEEELEE-LEAALRDLESRLGDLKKERDELEAQLRELERKIEELEAqieKKRKRLSELK 923
PH pfam00169
PH domain; PH stands for pleckstrin homology.
 771-873 6.03e-04

PH domain; PH stands for pleckstrin homology.


Pssm-ID: 459697 [Multi-domain]  Cd Length: 105  Bit Score: 40.62  E-value: 6.03e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  771 PTMKGLLTKVKHGYS---KRVWCTLIGKTLYYFRSQ---EDKFPLGQIKLWEAKVEEVDRSCDSDEDYeasgrsllstHY 844
Cdd:pfam00169    1 VVKEGWLLKKGGGKKkswKKRYFVLFDGSLLYYKDDksgKSKEPKGSISLSGCEVVEVVASDSPKRKF----------CF 70

                           90       100       110
                   ....*....|....*....|....*....|
gi 1034611600  845 TIVIHPKDQGPTYLLI-GSKHEKDTWLYHL 873
Cdd:pfam00169   71 ELRTGERTGKRTYLLQaESEEERKDWIKAI 100
RA_RASSF7_like cd16123
Ras-associating (RA) domain found in Ras-association domain family members, RASSF7, RASSF8, ...
 1082-1160 7.36e-04

Ras-associating (RA) domain found in Ras-association domain family members, RASSF7, RASSF8, RASSF9, and RASSF10; The RASSF family of proteins shares a conserved RalGDS/AF6 Ras association (RA) domain either in the C-terminus (RASSF1-6) or N-terminus (RASSF7-10). RASSF7-10 lacks a conserved SARAH (Salvador/RASSF/Hpo) motif adjacent to the RA domain that is found in members of the RASSF1-6 family. The structural differences between the C-terminus and N-terminus RASSF subgroups have led to the suggestion that they are two distinct families. RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub). Ras proteins are small GTPases that are involved in cellular signal transduction. The N-terminus RASSF proteins are potential Ras effectors that have been linked to key biological processes, including cell death, proliferation, microtubule stability, promoter methylation, vesicle trafficking and response to hypoxia.


Pssm-ID: 340540  Cd Length: 81  Bit Score: 39.92  E-value: 7.36e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600 1082 IPVhFMNGIYQVV-GFDASTTVEEFLNTLNQDTGMRKPAQSgFALFTddpSGRDLEHCLQGNIKICDIISKWEQASKEQQ 1160
Cdd:cd16123      2 LKV-WVDGEERVVsGVTERTTCQDVIYALAQATGQTNDTGR-YVLVE---RWRGIERPLPPRTRILKVWKAWGEEQSNVQ 76
PH_Skap1 cd13380
Src kinase-associated phosphoprotein 1 Pleckstrin homology (PH) domain; Adaptor protein Skap1 ...
 665-756 7.94e-04

Src kinase-associated phosphoprotein 1 Pleckstrin homology (PH) domain; Adaptor protein Skap1 (also called Skap55/Src kinase-associated phosphoprotein of 55 kDa) and its partner, ADAP (adhesion and degranulation promoting adapter protein) help reorganize the cytoskeleton and/or promote integrin-mediated adhesion upon immunoreceptor activation. Skap1 is also involved in T Cell Receptor (TCR)-induced RapL-Rap1 complex formation and LFA-1 activation. Skap1 has an N-terminal coiled-coil conformation which is proposed to be involved in homodimer formation, a central PH domain and a C-terminal SH3 domain that associates with ADAP. The Skap1 PH domain plays a role in controlling integrin function via recruitment of ADAP-SKAP complexes to integrins as well as in controlling the ability of ADAP to interact with the CBM signalosome and regulate NF-kappaB. SKAP1 is necessary for RapL binding to membranes in a PH domain-dependent manner and the PI3K pathway. Skap adaptor proteins couple receptors to cytoskeletal rearrangements. Skap55/Skap1, Skap2, and Skap-homology (Skap-hom) have an N-terminal coiled-coil conformation, a central PH domain and a C-terminal SH3 domain. Their PH domains bind 3'-phosphoinositides as well as directly affecting targets such as in Skap55 where it directly affecting integrin regulation by ADAP and NF-kappaB activation or in Skap-hom where the dimerization and PH domains comprise a 3'-phosphoinositide-gated molecular switch that controls ruffle formation. 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: 270180  Cd Length: 106  Bit Score: 40.61  E-value: 7.94e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKVK----SWKRRWFVLKGGELLYYKSPSDviRKPQGHIeLSASCSI-----LRGDNKQT--VQLTTE-KH 732
Cdd:cd13380      3 KQGYLEKRSKDHSffgsEWQKRWCVLTNRAFYYYASEKS--KQPKGGF-LIKGYSAqmaphLRKDSRRDscFELTTPgRR 79

                           90       100
                   ....*....|....*....|....
gi 1034611600  733 TYYLTADSPNILEEWIKVLQNVLR 756
Cdd:cd13380     80 TYQFTAASPSEARDWVDQIQFLLK 103
PH_CNK_mammalian-like cd01260
Connector enhancer of KSR (Kinase suppressor of ras) (CNK) pleckstrin homology (PH) domain; ...
 769-877 8.01e-04

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: 40.47  E-value: 8.01e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  769 GKPTMKGLLTKVKHGYS------KRVWCTLIGKTLYYFRSQEDKFPLGQIKLWEAKVEEVdRSCDSDEDYEASgrsllst 842
Cdd:cd01260     11 GRGDCQGWLWKKKEAKSffgqkwKKYWFVLKGSSLYWYSNQQDEKAEGFINLPDFKIERA-SECKKKYAFKAC------- 82

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1034611600  843 hytiviHPKDQgPTYLLIGSKHEKDTWLYHLTVAA 877
Cdd:cd01260     83 ------HPKIK-TFYFAAENLDDMNKWLSKLNMAI 110
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
 4-133 9.25e-04

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 43.89  E-value: 9.25e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    4 LERQVIDAERQAEKAfqqvqvmedkLKAANIQTSESETRLYNKCQDLESLIQEkddviqnlelqLEEQKQIRIQEAKIIE 83
Cdd:TIGR02168  198 LERQLKSLERQAEKA----------ERYKELKAELRELELALLVLRLEELREE-----------LEELQEELKEAEEELE 256

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1034611600   84 EKAAKIKEwVTVKLNELELENQNLRlinqnqtEEIRTMQSKLQEVQGKKS 133
Cdd:TIGR02168  257 ELTAELQE-LEEKLEELRLEVSELE-------EEIEELQKELYALANEIS 298
PRK03918 PRK03918
DNA double-strand break repair ATPase Rad50;
5-195 9.37e-04

DNA double-strand break repair ATPase Rad50;


Pssm-ID: 235175 [Multi-domain]  Cd Length: 880  Bit Score: 43.90  E-value: 9.37e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    5 ERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESE---TRLYNKCQDLESLIQEKDDVIQNLELQLEEQKQIRIQEAKI 81
Cdd:PRK03918   216 LPELREELEKLEKEVKELEELKEEIEELEKELESLEgskRKLEEKIRELEERIEELKKEIEELEEKVKELKELKEKAEEY 295

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600   82 IEEKaaKIKEWVTVKLNELELENQNLRlinqnqtEEIRTMQSKLQEVQGKKSSTVSTLKLSEG--QRLSSL-TFGCFLSR 158
Cdd:PRK03918   296 IKLS--EFYEEYLDELREIEKRLSRLE-------EEINGIEERIKELEEKEERLEELKKKLKEleKRLEELeERHELYEE 366

                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 1034611600  159 ARSppqvvKSEEMSKISSKEPEFTEGKDMEEMEIPEK 195
Cdd:PRK03918   367 AKA-----KKEELERLKKRLTGLTPEKLEKELEELEK 398
FERM_C2_myosin_like cd13204
FERM domain C-lobe, repeat 2, of Myosin-like proteins; These myosin-like proteins are ...
 1328-1404 9.75e-04

FERM domain C-lobe, repeat 2, of Myosin-like proteins; These myosin-like proteins are unidentified though they are sequence similar to myosin 1/myo1, myosin 7/myoVII, and myosin 10/myoX. These myosin-like proteins contain an N-terminal motor/head region and a C-terminal tail consisting of two myosin tail homology 4 (MyTH4) and twos FERM domains. In myoX the FERM domain forms a supramodule with its MyTH4 domain which binds to the negatively charged E-hook region in the tails of alpha- and beta-tubulin forming a proposed motorized link between actin filaments and microtubules and a similar thing might happen in these myosins. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The second FERM_N repeat is present in this hierarchy. The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 270025  Cd Length: 93  Bit Score: 39.72  E-value: 9.75e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1034611600 1328 LWLAVHEDGLSLLEYNSMRLIVSYVYKSLMTFGGYQDDFMVVinnTHSKDKPTEkllFAMAKPKILEITLLIASYIN 1404
Cdd:cd13204     19 LWLAIDQSGVHLLERRTKEPLCSYDYSSIVSYSPSLNSLMIV---TGSLTKGSK---FIFNTNQAFQIANLIRDYTH 89
SMC_prok_A TIGR02169
chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of ...
 6-145 9.88e-04

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274009 [Multi-domain]  Cd Length: 1164  Bit Score: 43.90  E-value: 9.88e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    6 RQVIDA-------ERQAEKAFQQVQVMEDKLKaaNIQTSESETRlynkcQDLESLIQEKDDVIQNLELQLEEQK---QIR 75
Cdd:TIGR02169  156 RKIIDEiagvaefDRKKEKALEELEEVEENIE--RLDLIIDEKR-----QQLERLRREREKAERYQALLKEKREyegYEL 228

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600   76 IQEAKIIEEKAAKI----------KEWVTVKLNELE---------LENQNLRlINQNQTEEIRTMQSKLQEVQGKKSSTV 136
Cdd:TIGR02169  229 LKEKEALERQKEAIerqlasleeeLEKLTEEISELEkrleeieqlLEELNKK-IKDLGEEEQLRVKEKIGELEAEIASLE 307


                   ....*....
gi 1034611600  137 STLKLSEGQ 145
Cdd:TIGR02169  308 RSIAEKERE 316
PH_PKB cd01241
Protein Kinase B-like pleckstrin homology (PH) domain; PKB (also called Akt), a member of the ...
 665-754 1.12e-03

Protein Kinase B-like pleckstrin homology (PH) domain; PKB (also called Akt), a member of the AGC kinase family, is a phosphatidylinositol 3'-kinase (PI3K)-dependent Ser/Thr kinase which alters the activity of the targeted protein. The name AGC is based on the three proteins that it is most similar to cAMP-dependent protein kinase 1 (PKA; also known as PKAC), cGMP-dependent protein kinase (PKG; also known as CGK1) and protein kinase C (PKC). Human Akt has three isoforms derived for distinct genes: Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma. All Akts have an N-terminal PH domain with an activating Thr phosphorylation site, a kinase domain, and a short C-terminal regulatory tail with an activating Ser phosphorylation site. The PH domain recruits Akt to the plasma membrane by binding to phosphoinositides (PtdIns-3,4-P2) and is required for activation. The phosphorylation of Akt at its Thr and Ser phosphorylation sites leads to increased Akt activity toward forkhead transcription factors, the mammalian target of rapamycin (mTOR), and the Bcl-xL/Bcl-2-associated death promoter (BAD), all of which possess a consensus motif R-X-R-XX-ST-B (X = amino acid, B = bulky hydrophobic residue) for Akt phosphorylation. 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: 269947  Cd Length: 107  Bit Score: 39.92  E-value: 1.12e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKVKSWKRRWFVLKG-GELLYYKspsdviRKPQGHIELS-------ASCSILRGDNKQT-------VQLTT 729
Cdd:cd01241      5 KEGWLLKRGEYIKNWRPRYFVLKSdGSFIGYK------EKPKPNQDPPplnnfsvAECQLMKTEKPKPntfiircLQWTT 78

                           90       100
                   ....*....|....*....|....*.
gi 1034611600  730 E-KHTYYltADSPNILEEWIKVLQNV 754
Cdd:cd01241     79 ViERTFH--VESEEEREEWMKAIQGV 102
SMC_prok_B TIGR02168
chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of ...
 1-148 1.32e-03

chromosome segregation protein SMC, common bacterial type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. This family represents the SMC protein of most bacteria. The smc gene is often associated with scpB (TIGR00281) and scpA genes, where scp stands for segregation and condensation protein. SMC was shown (in Caulobacter crescentus) to be induced early in S phase but present and bound to DNA throughout the cell cycle. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274008 [Multi-domain]  Cd Length: 1179  Bit Score: 43.51  E-value: 1.32e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    1 MQQLERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESETRLYNKCQDLESLIQEKDDVIQNLELQLEEQKQiriqeak 80
Cdd:TIGR02168  826 LESLERRIAATERRLEDLEEQIEELSEDIESLAAEIEELEELIEELESELEALLNERASLEEALALLRSELEE------- 898

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600   81 iieekaakikewVTVKLNELELENQNLRlinqNQTEEIRTMQSKLQEVQGKKSSTVSTL--KLSEGQRLS 148
Cdd:TIGR02168  899 ------------LSEELRELESKRSELR----RELEELREKLAQLELRLEGLEVRIDNLqeRLSEEYSLT 952
Mplasa_alph_rch TIGR04523
helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of ...
 2-151 1.68e-03

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.


Pssm-ID: 275316 [Multi-domain]  Cd Length: 745  Bit Score: 43.09  E-value: 1.68e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    2 QQLERQVIDAERQAEKAF-----QQVQVMEDKLKAANIQTSESE---TRLYNKCQDLESLIQEKDDVIQNLELQLEEqKQ 73
Cdd:TIGR04523  291 NQLKSEISDLNNQKEQDWnkelkSELKNQEKKLEEIQNQISQNNkiiSQLNEQISQLKKELTNSESENSEKQRELEE-KQ 369

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034611600   74 IRIQeaKIIEEKAAKIKEwvtvkLNELELENQNLRLINQNQTEEIRTMQSKLQEVQGKKSstvstLKLSEGQRLSSLT 151
Cdd:TIGR04523  370 NEIE--KLKKENQSYKQE-----IKNLESQINDLESKIQNQEKLNQQKDEQIKKLQQEKE-----LLEKEIERLKETI 435
PH_GRP1-like cd01252
General Receptor for Phosphoinositides-1-like Pleckstrin homology (PH) domain; GRP1/cytohesin3 ...
 769-823 1.68e-03

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: 39.99  E-value: 1.68e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1034611600  769 GKPTMKGLLTKV--KHGYSKRVWCTLIGKTLYYFRSQEDKFPLGQIKLWEAKVEEVD 823
Cdd:cd01252      1 FNPDREGWLLKLggRVKSWKRRWFILTDNCLYYFEYTTDKEPRGIIPLENLSVREVE 57
PH2_PH_fungal cd13299
Fungal proteins Pleckstrin homology (PH) domain, repeat 2; The functions of these fungal ...
 667-755 1.90e-03

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


Pssm-ID: 270111  Cd Length: 102  Bit Score: 39.15  E-value: 1.90e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  667 GYLLKMSGK-VKSWKRRWFVLKGGELLYYKSPSDVirKPQGHIELSASCSI-----LRGDNKQTVQLTTEKHTYYLTADS 740
Cdd:cd13299     10 GYLQVLKKKgVNQWKKYWLVLRNRSLSFYKDQSEY--SPVKIIPIDDIIDVveldpLSKSKKWCLQIITPEKRIRFCADD 87

                           90
                   ....*....|....*
gi 1034611600  741 PNILEEWIKVLQNVL 755
Cdd:cd13299     88 EESLIKWLGALKSLL 102
SMC_N pfam02463
RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The ...
 4-203 1.91e-03

RecF/RecN/SMC N terminal domain; This domain is found at the N terminus of SMC proteins. The SMC (structural maintenance of chromosomes) superfamily proteins have ATP-binding domains at the N- and C-termini, and two extended coiled-coil domains separated by a hinge in the middle. The eukaryotic SMC proteins form two kind of heterodimers: the SMC1/SMC3 and the SMC2/SMC4 types. These heterodimers constitute an essential part of higher order complexes, which are involved in chromatin and DNA dynamics. This family also includes the RecF and RecN proteins that are involved in DNA metabolism and recombination.


Pssm-ID: 426784 [Multi-domain]  Cd Length: 1161  Bit Score: 43.04  E-value: 1.91e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    4 LERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESETRLYNKCQDL---ESLIQEKDDVIQNLELQLEEQKQIRIQEAK 80
Cdd:pfam02463  195 LKLQELKLKEQAKKALEYYQLKEKLELEEEYLLYLDYLKLNEERIDLlqeLLRDEQEEIESSKQEIEKEEEKLAQVLKEN 274

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600   81 IIEEKAAKIKEWVTVKLNELELENQNLRLINQNQTEEIRTMQSKLQEVQGKKSSTVSTLKLSEGQRLSSLTfgcFLSRAR 160
Cdd:pfam02463  275 KEEEKEKKLQEEELKLLAKEEEELKSELLKLERRKVDDEEKLKESEKEKKKAEKELKKEKEEIEELEKELK---ELEIKR 351

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1034611600  161 SPPQVVKSEEMSK----ISSKEPEFTEGKDMEEMEIPEKSVDNQVLE 203
Cdd:pfam02463  352 EAEEEEEEELEKLqeklEQLEEELLAKKKLESERLSSAAKLKEEELE 398
PH_PLEKHJ1 cd13258
Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; ...
 670-753 1.93e-03

Pleckstrin homology domain containing, family J member 1 Pleckstrin homology (PH) domain; PLEKHJ1 (also called GNRPX2/Guanine nucleotide-releasing protein x ). It contains a single PH domain. Very little information is known about PLEKHJ1. PLEKHJ1 has been shown to interact with IKBKG (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma) and KRT33B (keratin 33B). 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: 270078  Cd Length: 123  Bit Score: 39.61  E-value: 1.93e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  670 LKMSGKVKS--WKRRWFVLKGGELLYYKS-PSDVIRKPQGHIELSaSCSILRGDNKQTVQLTT-------EKHtYYLTAD 739
Cdd:cd13258     25 RQMGGPKKSevFKERWFKLKGNLLFYFRTnEFGDCSEPIGAIVLE-NCRVQMEEITEKPFAFSivfndepEKK-YIFSCR 102

                           90
                   ....*....|....
gi 1034611600  740 SPNILEEWIKVLQN 753
Cdd:cd13258    103 SEEQCEQWIEALRQ 116
PH_Osh1p_Osh2p_yeast cd13292
Yeast oxysterol binding protein homologs 1 and 2 Pleckstrin homology (PH) domain; Yeast Osh1p ...
 771-819 2.03e-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: 39.21  E-value: 2.03e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1034611600  771 PTMKGLLTK---VKHGYSKRvWCTLIGKTLYYFRSQED--KFPLGQIKLWEAKV 819
Cdd:cd13292      2 PTMKGYLKKwtnYAKGYKTR-WFVLEDGVLSYYRHQDDegSACRGSINMKNARL 54
PTZ00332 PTZ00332
paraflagellar rod protein; Provisional
 2-140 2.15e-03

paraflagellar rod protein; Provisional


Pssm-ID: 240364 [Multi-domain]  Cd Length: 589  Bit Score: 42.64  E-value: 2.15e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    2 QQLERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSesetrlynkcqdleslIQEKDDVIQNLELQLEEQKQIRIQEAKI 81
Cdd:PTZ00332   144 EELRRSQLDATQLAQVPTATLKNIEDIMNVTQIQNA----------------LASTDDQIKTQLAQLEKTNEIQNVAMHD 207

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1034611600   82 IEEKAAKIKEWVTVKLNE--LELENQNLRLInqNQTEEIRTMQSKLQEVQGKKSSTVSTLK 140
Cdd:PTZ00332   208 GEMQVAEEQMWTKVQLQErlIELVADKFRLI--GKCEEENKSFSKIHEVQKQANQETSQMK 266
PH-GRAM1_AGT26 cd13215
Autophagy-related protein 26/Sterol 3-beta-glucosyltransferase Pleckstrin homology (PH) domain, ...
 767-869 2.52e-03

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: 39.14  E-value: 2.52e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  767 PEGKPTMKGLLTKV--KHGYSKRVWCTLIGKTLYYFRSQEDK-FPLGQIKLweAKVEEVDRSCDSDEDyeasgrsllSTH 843
Cdd:cd13215     17 RSGAVIKSGYLSKRskRTLRYTRYWFVLKGDTLSWYNSSTDLyFPAGTIDL--RYATSIELSKSNGEA---------TTS 85

                           90       100
                   ....*....|....*....|....*..
gi 1034611600  844 YTIVIHPKdqgpTYLLI-GSKHEKDTW 869
Cdd:cd13215     86 FKIVTNSR----TYKFKaDSETSADEW 108
PRK00409 PRK00409
recombination and DNA strand exchange inhibitor protein; Reviewed
 16-153 2.77e-03

recombination and DNA strand exchange inhibitor protein; Reviewed


Pssm-ID: 234750 [Multi-domain]  Cd Length: 782  Bit Score: 42.12  E-value: 2.77e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600   16 EKAfqQVQVMEDKLKAAN-IQTSE-SETRLYNKCQDLESLIQEKDDVIQNLELQLEEQKQIR---IQEAkiiEEKAAKI- 89
Cdd:PRK00409   505 EEA--KKLIGEDKEKLNElIASLEeLERELEQKAEEAEALLKEAEKLKEELEEKKEKLQEEEdklLEEA---EKEAQQAi 579

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1034611600   90 ----KEWVTVKLNELELENQNLRLINQNQTEEIRT----MQSKLQEVQGKKSSTVSTLKlsEGQRLSSLTFG 153
Cdd:PRK00409   580 keakKEADEIIKELRQLQKGGYASVKAHELIEARKrlnkANEKKEKKKKKQKEKQEELK--VGDEVKYLSLG 649
FERM_C_MyoX cd13202
FERM domain C-lobe of Myosin X (MyoX, Myo10); MyoX, a MyTH-FERM myosin, is a molecular motor ...
 1328-1404 3.49e-03

FERM domain C-lobe of Myosin X (MyoX, Myo10); 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 MyoX FERM domain binds to the NPXY motif of several beta-integrins, a key family of cell surface receptors that are involved in cell adhesion and migration. In addition the FERM domain binds to the cytoplasmic domains of the netrin receptors DCC (deleted in colorectal cancer) and neogenin. The FERM domain also forms a supramodule with its MyTH4 domain which binds to the negatively charged E-hook region in the tails of alpha- and beta-tubulin forming a proposed motorized link between actin filaments and microtubules. The FERM domain has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobe or F3). The C-lobe/F3 within the FERM domain is part of the PH domain family. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs), the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites.


Pssm-ID: 270023  Cd Length: 90  Bit Score: 38.14  E-value: 3.49e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1034611600 1328 LWLAVHEDGLSLLEYNSMRLIVSYVYKSLMTFGGYQDD-FMVVInnthskDKPTEkLLFamAKPKILEITLLIASYIN 1404
Cdd:cd13202     18 LWLGVSAEGVSLYKRGESKPLESFPYEHILSFGAPQANtYKIVV------DGDRP-MLF--ETTQVVEIAKLMKAYIN 86
SMC_prok_A TIGR02169
chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of ...
 2-151 3.69e-03

chromosome segregation protein SMC, primarily archaeal type; SMC (structural maintenance of chromosomes) proteins bind DNA and act in organizing and segregating chromosomes for partition. SMC proteins are found in bacteria, archaea, and eukaryotes. It is found in a single copy and is homodimeric in prokaryotes, but six paralogs (excluded from this family) are found in eukarotes, where SMC proteins are heterodimeric. This family represents the SMC protein of archaea and a few bacteria (Aquifex, Synechocystis, etc); the SMC of other bacteria is described by TIGR02168. The N- and C-terminal domains of this protein are well conserved, but the central hinge region is skewed in composition and highly divergent. [Cellular processes, Cell division, DNA metabolism, Chromosome-associated proteins]


Pssm-ID: 274009 [Multi-domain]  Cd Length: 1164  Bit Score: 41.98  E-value: 3.69e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    2 QQLERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESETRLYNKCQDLESLIQEK-----------DDVIQNLELQLEE 70
Cdd:TIGR02169  240 EAIERQLASLEEELEKLTEEISELEKRLEEIEQLLEELNKKIKDLGEEEQLRVKEKigeleaeiaslERSIAEKERELED 319

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600   71 -QKQIRIQEAKI--IEEKAAKIKEwvtvKLNELELENQNLRLINQNQTEEIRTMQSKLQEVQGKKSSTVSTLKlSEGQRL 147
Cdd:TIGR02169  320 aEERLAKLEAEIdkLLAEIEELER----EIEEERKRRDKLTEEYAELKEELEDLRAELEEVDKEFAETRDELK-DYREKL 394


                   ....
gi 1034611600  148 SSLT 151
Cdd:TIGR02169  395 EKLK 398
PH_MELT_VEPH1 cd01264
Melted pleckstrin homology (PH) domain; The melted protein (also called Ventricular zone ...
 676-752 3.80e-03

Melted pleckstrin homology (PH) domain; The melted protein (also called Ventricular zone expressed PH domain-containing protein homolog 1) is expressed in the developing central nervous system of vertebrates. It contains a single C-terminal PH domain that is required for membrane targeting. 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: 269965  Cd Length: 105  Bit Score: 38.59  E-value: 3.80e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  676 VKSWKRRWFVLKGGELLYYKSPSDVIRKPqghIELSA--SCSILRGDNK---QTVQLTTEKHTYYLTADSPNILEEWIKV 750
Cdd:cd01264     18 FKRWRTRYFTLSGAQLSYRGGKSKPDAPP---IELSKirSVKVVRKKDRsipKAFEIFTDDKTYVLKAKDEKNAEEWLQC 94


                   ..
gi 1034611600  751 LQ 752
Cdd:cd01264     95 LS 96
PH_PEPP1_2_3 cd13248
Phosphoinositol 3-phosphate binding proteins 1, 2, and 3 pleckstrin homology (PH) domain; ...
 767-814 3.84e-03

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: 38.41  E-value: 3.84e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1034611600  767 PEGKPTMKGLLTK-----VKHgYSKRvWCTLIGKTLYYFRSQEDKFPLGQIKL 814
Cdd:cd13248      3 PNAPVVMSGWLHKqggsgLKN-WRKR-WFVLKDNCLYYYKDPEEEKALGSILL 53
Mplasa_alph_rch TIGR04523
helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of ...
 2-200 5.50e-03

helix-rich Mycoplasma protein; Members of this family occur strictly within a subset of Mycoplasma species. Members average 750 amino acids in length, including signal peptide. Sequences are predicted (Jpred 3) to be almost entirely alpha-helical. These sequences show strong periodicity (consistent with long alpha helical structures) and low complexity rich in D,E,N,Q, and K. Genes encoding these proteins are often found in tandem. The function is unknown.


Pssm-ID: 275316 [Multi-domain]  Cd Length: 745  Bit Score: 41.16  E-value: 5.50e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    2 QQLERQVIDAERQAEKAFQQVQVMEDKLKAANIQTSESE---TRLYNKCQDLESLIQEKDDVIQNLELQLEEQKQIRIQE 78
Cdd:TIGR04523  387 KNLESQINDLESKIQNQEKLNQQKDEQIKKLQQEKELLEkeiERLKETIIKNNSEIKDLTNQDSVKELIIKNLDNTRESL 466

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600   79 AKIIEEKAAKIKEwvtvklNELELENQNLRLINQNQ-----TEEIRTMQSKLQEVQGKKSStvstLKLSEgQRLSSLtfg 153
Cdd:TIGR04523  467 ETQLKVLSRSINK------IKQNLEQKQKELKSKEKelkklNEEKKELEEKVKDLTKKISS----LKEKI-EKLESE--- 532

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1034611600  154 cflsrarsppqvvKSEEMSKISSKEPEFTEGKDMEEMEIPEKSVDNQ 200
Cdd:TIGR04523  533 -------------KKEKESKISDLEDELNKDDFELKKENLEKEIDEK 566
PRK12704 PRK12704
phosphodiesterase; Provisional
 2-101 5.52e-03

phosphodiesterase; Provisional


Pssm-ID: 237177 [Multi-domain]  Cd Length: 520  Bit Score: 40.92  E-value: 5.52e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    2 QQLERQVIDAERQA------------EKAFQQVQVMEDKLKAANIQTSESETRLYNKcqdlESLIQEKDDVIQNLELQLE 69
Cdd:PRK12704    38 EEAKRILEEAKKEAeaikkealleakEEIHKLRNEFEKELRERRNELQKLEKRLLQK----EENLDRKLELLEKREEELE 113

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1034611600   70 EQKQIRIQEAKIIEEKAAKIKEWVTVKLNELE 101
Cdd:PRK12704   114 KKEKELEQKQQELEKKEEELEELIEEQLQELE 145
PH cd00821
Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...
 773-873 5.97e-03

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: 37.52  E-value: 5.97e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  773 MKGLLTKVKHGYS---KRVWCTLIGKTLYYFRSQED--KFPLGQIKLWE-AKVEEVDRScdsdedyeasgrsllSTHYTI 846
Cdd:cd00821      1 KEGYLLKRGGGGLkswKKRWFVLFEGVLLYYKSKKDssYKPKGSIPLSGiLEVEEVSPK---------------ERPHCF 65

                           90       100
                   ....*....|....*....|....*..
gi 1034611600  847 VIHPKDQGPTYLLIGSKHEKDTWLYHL 873
Cdd:cd00821     66 ELVTPDGRTYYLQADSEEERQEWLKAL 92
CENP-F_leu_zip pfam10473
Leucine-rich repeats of kinetochore protein Cenp-F/LEK1; Cenp-F, a centromeric kinetochore, ...
 16-146 8.66e-03

Leucine-rich repeats of kinetochore protein Cenp-F/LEK1; Cenp-F, a centromeric kinetochore, microtubule-binding protein consisting of two 1,600-amino acid-long coils, is essential for the full functioning of the mitotic checkpoint pathway. There are several leucine-rich repeats along the sequence of LEK1 that are considered to be zippers, though they do not appear to be binding DNA directly in this instance.


Pssm-ID: 463102 [Multi-domain]  Cd Length: 140  Bit Score: 38.05  E-value: 8.66e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600   16 EKAFQQvqvMEDKLKaaniqtsESETRLYNKCQDLESLIQEKDDVIQNLE---LQLEEQKqiriqeaKIIEEKAAKIKEw 92
Cdd:pfam10473    2 EKKQLH---VLEKLK-------ESERKADSLKDKVENLERELEMSEENQElaiLEAENSK-------AEVETLKAEIEE- 63

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1034611600   93 VTVKLNELELENQNLRLINQNQTEEIRTMQSKLQEVQGKKSSTVSTLKLSEGQR 146
Cdd:pfam10473   64 MAQNLRDLELDLVTLRSEKENLTKELQKKQERVSELESLNSSLENLLEEKEQEK 117
PH_RASAL1 cd13369
Ras-GTPase-activating-like protein pleckstrin homology (PH) domain; RASAL1 is a member of the ...
 665-754 9.41e-03

Ras-GTPase-activating-like protein pleckstrin homology (PH) domain; RASAL1 is a member of the GAP1 family of GTPase-activating proteins, along with GAP1(m), GAP1(IP4BP) and CAPRI. RASAL1 contains two C2 domains, a PH domain, a RasGAP domain, and a BTK domain. RASAL1 contains two fully conserved C2 domains, a PH domain, a RasGAP domain, and a BTK domain. Its catalytic GAP domain has dual RasGAP and RapGAP activities, while its C2 domains bind phospholipids in the presence of Ca2+. Both CAPRI and RASAL1 are calcium-activated RasGAPs that inactivate Ras at the plasma membrane. Thereby enhancing the weak intrinsic GTPase activity of RAS proteins resulting in the inactive GDP-bound form of RAS and allowing control of cellular proliferation and differentiation. CAPRI and RASAL1 differ in that CAPRI is an amplitude sensor while RASAL1 senses calcium oscillations. This difference between them resides not in their C2 domains, but in their PH domains leading to speculation that this might reflect an association with either phosphoinositides and/or 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: 270175  Cd Length: 138  Bit Score: 37.92  E-value: 9.41e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600  665 KSGYLLKMSGKVKS------WKRRWFVLKGGELLYYKSPSDVIRKPqghIELSASCSILRGDN-----KQTVQLTT---- 729
Cdd:cd13369     17 KEGYLHKRKAEGVGlvtrftFKKRYFWLSSETLSYSKSPDWQVRSS---IPVQRICAVERVDEnafqqPNVMQVVTqdge 93

                           90       100
                   ....*....|....*....|....*.
gi 1034611600  730 -EKHTYYLTADSPNILEEWIKVLQNV 754
Cdd:cd13369     94 gQVHTTYIQCKNVNELNQWLSALRKV 119
COG4372 COG4372
Uncharacterized protein, contains DUF3084 domain [Function unknown];
8-134 9.89e-03

Uncharacterized protein, contains DUF3084 domain [Function unknown];


Pssm-ID: 443500 [Multi-domain]  Cd Length: 370  Bit Score: 39.89  E-value: 9.89e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034611600    8 VIDAERQAEKAFQQVQVMEDKLKAANIQTSESETRLYNKCQDLESLIQEKDDVIQNLE---LQLEE-QKQIRIQEAKI-- 81
Cdd:COG4372     26 IAALSEQLRKALFELDKLQEELEQLREELEQAREELEQLEEELEQARSELEQLEEELEelnEQLQAaQAELAQAQEELes 105

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1034611600   82 IEEKAAKIKEwvtvKLNELELENQNLRLINQNQTEEIRTMQSKLQEVQGKKSS 134
Cdd:COG4372    106 LQEEAEELQE----ELEELQKERQDLEQQRKQLEAQIAELQSEIAEREEELKE 154
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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