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

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 768010233  47 FADSREESVLGSVLLPSYNIRPDGPGAPRGRRFTFTAEHPGMRTYVLAADTLEDLRGWLRALGRAS 112
Cdd:cd13248   39 YKDPEEEKALGSILLPSYTISPAPPSDEISRKFAFKAEHANMRTYYFAADTAEEMEQWMNAMSLAA 104

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768010233  464 PPPHTEPDSPSPVLQGEESseRESLPEslELSSPRSPETDWGRPPGG--------DKDLASPHLGLGSPRVSRASSPEGR 535
Cdd:PHA03247 2569 PPPRPAPRPSEPAVTSRAR--RPDAPP--QSARPRAPVDDRGDPRGPappsplppDTHAPDPPPPSPSPAANEPDPHPPP 2644

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768010233  536 HLPSPQLGTKAPvARPRMSAQEQLERMRRNQECGRPFPRPTSPRLLTLGRTLSPARRQPDVEQRPVvghsgaqkwlrssg 615
Cdd:PHA03247 2645 TVPPPERPRDDP-APGRVSRPRRARRLGRAAQASSPPQRPRRRAARPTVGSLTSLADPPPPPPTPE-------------- 2709

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768010233  616 swSSPRNTTPYLPTSEG---HRERVLSLSQALATEASQWHRMMTGGNLDSQGDPLPGVPLPPSDPTRQETPPPRSPPVAN 692
Cdd:PHA03247 2710 --PAPHALVSATPLPPGpaaARQASPALPAAPAPPAVPAGPATPGGPARPARPPTTAGPPAPAPPAAPAAGPPRRLTRPA 2787

                         250       260       270
                  ....*....|....*....|....*....|....
gi 768010233  693 SGStgfsrRGSGRGGGPTPWGPAWDAGIAPPVLP 726
Cdd:PHA03247 2788 VAS-----LSESRESLPSPWDPADPPAAVLAPAA 2816

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 768010233  47 FADSREESVLGSVLLPSYNIRPDGPGAPRGRRFTFTAEHPGMRTYVLAADTLEDLRGWLRALGRAS 112
Cdd:cd13248   39 YKDPEEEKALGSILLPSYTISPAPPSDEISRKFAFKAEHANMRTYYFAADTAEEMEQWMNAMSLAA 104

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768010233 339 DRLLRRLQEeIDQKQEEKEQLEAALELTRQQLGQATREAGApgRAWGRQRLLQDRLVSVRATLCHLTQERERvwdtysgL 418
Cdd:COG4717  149 EELEERLEE-LRELEEELEELEAELAELQEELEELLEQLSL--ATEEELQDLAEELEELQQRLAELEEELEE-------A 218

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 768010233 419 EQELGTLRETLEYL---LHLGSPQDRVSAQQQLWMVEDTLAGLGG 460
Cdd:COG4717  219 QEELEELEEELEQLeneLEAAALEERLKEARLLLLIAAALLALLG 263

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 768010233   49 DSREESVLGSVLLPSYNIRPDGPGAPRGRRFTF---TAEHPGMRTYVLAADTLEDLRGWLRALGRASR 113
Cdd:pfam00169  38 SGKSKEPKGSISLSGCEVVEVVASDSPKRKFCFelrTGERTGKRTYLLQAESEEERKDWIKAIQSAIR 105

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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 768010233  47 FADSREESVLGSVLLPSYNIRPDGPGAPRGRRFTFTAEHPGMRTYVLAADTLEDLRGWLRALGRAS 112
Cdd:cd13248   39 YKDPEEEKALGSILLPSYTISPAPPSDEISRKFAFKAEHANMRTYYFAADTAEEMEQWMNAMSLAA 104

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|..
gi 768010233  73 APRGRRFTFTAEH--PGMRTYVLAADTLEDLRGWLRALGRAS 112
Cdd:cd13288   61 AEDAEPYAFAIRFdgPGARSYVLAAENQEDMESWMKALSRAS 102

Uncharacterized conserved protein YhaN, contains AAA domain [Function unknown];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768010233 339 DRLLRRLQEeIDQKQEEKEQLEAALELTRQQLGQATREAGApgRAWGRQRLLQDRLVSVRATLCHLTQERERvwdtysgL 418
Cdd:COG4717  149 EELEERLEE-LRELEEELEELEAELAELQEELEELLEQLSL--ATEEELQDLAEELEELQQRLAELEEELEE-------A 218

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*
gi 768010233 419 EQELGTLRETLEYL---LHLGSPQDRVSAQQQLWMVEDTLAGLGG 460
Cdd:COG4717  219 QEELEELEEELEQLeneLEAAALEERLKEARLLLLIAAALLALLG 263

Uncharacterized protein, contains DUF3084 domain [Function unknown];

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768010233 342 LRRLQEEIDQKQEEKEQLEAALELTRQQLGQAtreagapgrawgRQRL--LQDRLVSVRATLCHLTQERERVwdtysglE 419
Cdd:COG4372   47 LEQLREELEQAREELEQLEEELEQARSELEQL------------EEELeeLNEQLQAAQAELAQAQEELESL-------Q 107

                         90
                 ....*....|.
gi 768010233 420 QELGTLRETLE 430
Cdd:COG4372  108 EEAEELQEELE 118

Phospholipase C-gamma Split pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated by receptor and non-receptor tyrosine kinases due to the presence of its SH2 and SH3 domains. There are two main isoforms of PLC-gamma expressed in human specimens, PLC-gamma1 and PLC-gamma2. PLC-gamma consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves internal to which is a PH domain split by two SH2 domains and a single SH3 domain, and a C-terminal C2 domain. The split PH domain is present in this hierarchy. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). 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.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 768010233  47 FADSREESVLGSVL-----LPSYNI--RPDGPGaprGRRFTFTAE--HPGMRTYVLAADTLEDLRGWLR 106
Cdd:cd13234   31 YSEETENSPLGSLLrgildVPSCHVvkRPEGKN---SRPFVFILSpkSLSDPPLDVAADSQEELQDWVQ 96

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

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 768010233 342 LRRLQEEIDQKQEEKEQLEAALELTRQQLGQATREAGApgrAWGRQRLLQDRLVSVRATLCHLTQERERVWDTYSGLEQE 421
Cdd:COG1196  248 LEELEAELEELEAELAELEAELEELRLELEELELELEE---AQAEEYELLAELARLEQDIARLEERRRELEERLEELEEE 324

                 ....*....
gi 768010233 422 LGTLRETLE 430
Cdd:COG1196  325 LAELEEELE 333

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.

                         10        20        30
                 ....*....|....*....|....*....|....*
gi 768010233  74 PRGRRFTFTAEHPGMRTYVLAADTLEDLRGWLRAL 108
Cdd:cd00821   58 PKERPHCFELVTPDGRTYYLQADSEEERQEWLKAL 92

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.

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*....
gi 768010233  64 YNIRPDGP-GAPRGRRFTFTAEHPGmRTYVLAADTLEDLRGWLRALGRA 111
Cdd:cd01251   55 YSVREGLPpGIKGHWGFGFTLVTPD-RTFLLSAETEEERREWITAIQKV 102