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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958798354  993 TVEEKGFLTIFEDVSGFGAWHRRWCVLSGNCISYWTYPDDERRKNPIGRINLANCISHQIEPANREFCARRNTLELITVR 1072
Cdd:cd01263      1 SVEYRGFLTVFEDVSGLGAWHRRWCVLRGGYLSFWKYPDDEEKKKPIGSIDLTKCITEKVEPAPRELCARPNTFLLETLR 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1958798354 1073 PQREDDREtlvsqcrDTLCVTKNWLSADTKEERDLWMQKLNQVIVDIR 1120
Cdd:cd01263     81 PAEDDDRD-------DTNEKIRVLLSADTKEERIEWLSALNQTLADLR 121

Anillin N-terminus; This domain is found towards the N-terminus of anillin. In mammalian anillin this domain is repeated. This domain overlaps with the region responsible for nuclear localization of anillin.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958798354  135 VKTRMQKLAEQRRHWDSE-ITDDVSESSHFSPMPSEEKPASPSKPPVSnaSATPVGRRGRLANLAATICSWEDDVSYSSA 213
Cdd:pfam16018    1 VKSRMQKLAEQRRRWDNDdWSDDVPESSPVSPLKSEAEAASPPKPITS--SETPVGRRGRLANLAATIGSWEDDLSHPSI 78

                   ....*...
gi 1958798354  214 KQNSVQEQ 221
Cdd:pfam16018   79 PQNPAQEK 86

transcriptional regulator ICP4; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958798354   26 RPTAAARSAPHAKRGREP-------LSEASNQQQPLLAGGEEKSCTKPSPSKKRCSDKIEVEAsdlenkepvdAAKPCSP 98
Cdd:PHA03307   211 SPISASASSPAPAPGRSAaddagasSSDSSSSESSGCGWGPENECPLPRPAPITLPTRIWEAS----------GWNGPSS 280

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958798354   99 KPAPRqmKPPAPAAISDSVAAPASLLSTGKASTTSSVKTRmqklaEQRRHWDSEITDDVSESSH---FSPMPSEEKPASP 175
Cdd:PHA03307   281 RPGPA--SSSSSPRERSPSPSPSSPGSGPAPSSPRASSSS-----SSSRESSSSSTSSSSESSRgaaVSPGPSPSRSPSP 353

                          170       180
                   ....*....|....*....|....*
gi 1958798354  176 SKPPVSNASATPvGRRGRLANLAAT 200
Cdd:PHA03307   354 SRPPPPADPSSP-RKRPRPSRAPSS 377

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958798354  993 TVEEKGFLTIFEDVSGFGAWHRRWCVLSGNCISYWTYPDDERRKNPIGRINLANCISHQIEPANREFCARRNTLELITVR 1072
Cdd:cd01263      1 SVEYRGFLTVFEDVSGLGAWHRRWCVLRGGYLSFWKYPDDEEKKKPIGSIDLTKCITEKVEPAPRELCARPNTFLLETLR 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1958798354 1073 PQREDDREtlvsqcrDTLCVTKNWLSADTKEERDLWMQKLNQVIVDIR 1120
Cdd:cd01263     81 PAEDDDRD-------DTNEKIRVLLSADTKEERIEWLSALNQTLADLR 121

Anillin N-terminus; This domain is found towards the N-terminus of anillin. In mammalian anillin this domain is repeated. This domain overlaps with the region responsible for nuclear localization of anillin.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958798354  135 VKTRMQKLAEQRRHWDSE-ITDDVSESSHFSPMPSEEKPASPSKPPVSnaSATPVGRRGRLANLAATICSWEDDVSYSSA 213
Cdd:pfam16018    1 VKSRMQKLAEQRRRWDNDdWSDDVPESSPVSPLKSEAEAASPPKPITS--SETPVGRRGRLANLAATIGSWEDDLSHPSI 78

                   ....*...
gi 1958798354  214 KQNSVQEQ 221
Cdd:pfam16018   79 PQNPAQEK 86

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958798354  997 KGFLTIFEDVSGFGaWHRRWCVLSGNCISYWTYPDDERRKNPIGRINLANCIShqIEPANREFCARRNTLELITVRPQRe 1076
Cdd:pfam00169    4 EGWLLKKGGGKKKS-WKKRYFVLFDGSLLYYKDDKSGKSKEPKGSISLSGCEV--VEVVASDSPKRKFCFELRTGERTG- 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1958798354 1077 ddRETLVsqcrdtlcvtknwLSADTKEERDLWMQKLNQVI 1116
Cdd:pfam00169   80 --KRTYL-------------LQAESEEERKDWIKAIQSAI 104

transcriptional regulator ICP4; Provisional

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958798354   26 RPTAAARSAPHAKRGREP-------LSEASNQQQPLLAGGEEKSCTKPSPSKKRCSDKIEVEAsdlenkepvdAAKPCSP 98
Cdd:PHA03307   211 SPISASASSPAPAPGRSAaddagasSSDSSSSESSGCGWGPENECPLPRPAPITLPTRIWEAS----------GWNGPSS 280

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958798354   99 KPAPRqmKPPAPAAISDSVAAPASLLSTGKASTTSSVKTRmqklaEQRRHWDSEITDDVSESSH---FSPMPSEEKPASP 175
Cdd:PHA03307   281 RPGPA--SSSSSPRERSPSPSPSSPGSGPAPSSPRASSSS-----SSSRESSSSSTSSSSESSRgaaVSPGPSPSRSPSP 353

                          170       180
                   ....*....|....*....|....*
gi 1958798354  176 SKPPVSNASATPvGRRGRLANLAAT 200
Cdd:PHA03307   354 SRPPPPADPSSP-RKRPRPSRAPSS 377

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958798354  993 TVEEKGFLTIFEDVSGFGAWHRRWCVLSGNCISYWTYPDDERRKNPIGRINLANCISHQIEPANREFCARRNTLELITVR 1072
Cdd:cd01263      1 SVEYRGFLTVFEDVSGLGAWHRRWCVLRGGYLSFWKYPDDEEKKKPIGSIDLTKCITEKVEPAPRELCARPNTFLLETLR 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*...
gi 1958798354 1073 PQREDDREtlvsqcrDTLCVTKNWLSADTKEERDLWMQKLNQVIVDIR 1120
Cdd:cd01263     81 PAEDDDRD-------DTNEKIRVLLSADTKEERIEWLSALNQTLADLR 121

Anillin N-terminus; This domain is found towards the N-terminus of anillin. In mammalian anillin this domain is repeated. This domain overlaps with the region responsible for nuclear localization of anillin.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958798354  135 VKTRMQKLAEQRRHWDSE-ITDDVSESSHFSPMPSEEKPASPSKPPVSnaSATPVGRRGRLANLAATICSWEDDVSYSSA 213
Cdd:pfam16018    1 VKSRMQKLAEQRRRWDNDdWSDDVPESSPVSPLKSEAEAASPPKPITS--SETPVGRRGRLANLAATIGSWEDDLSHPSI 78

                   ....*...
gi 1958798354  214 KQNSVQEQ 221
Cdd:pfam16018   79 PQNPAQEK 86

PH domain; PH stands for pleckstrin homology.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958798354  997 KGFLTIFEDVSGFGaWHRRWCVLSGNCISYWTYPDDERRKNPIGRINLANCIShqIEPANREFCARRNTLELITVRPQRe 1076
Cdd:pfam00169    4 EGWLLKKGGGKKKS-WKKRYFVLFDGSLLYYKDDKSGKSKEPKGSISLSGCEV--VEVVASDSPKRKFCFELRTGERTG- 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1958798354 1077 ddRETLVsqcrdtlcvtknwLSADTKEERDLWMQKLNQVI 1116
Cdd:pfam00169   80 --KRTYL-------------LQAESEEERKDWIKAIQSAI 104

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958798354 1012 WHRRWCVLSGNCISYWTYPDDerrKNPIGRINLANCISHQIEPANREFCarrntLELITvrpqreDDRETLVSQCR---D 1088
Cdd:cd01252     19 WKRRWFILTDNCLYYFEYTTD---KEPRGIIPLENLSVREVEDKKKPFC-----FELYS------PSNGQVIKACKtdsD 84

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1958798354 1089 TLCVTKN----WLSADTKEERDLWMQKLNQVI 1116
Cdd:cd01252     85 GKVVEGNhtvyRISAASEEERDEWIKSIKASI 116

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        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958798354 1007 SGFGAWHRRWCVLSGNCISYwtYPDDERRKnPIGRINLAnciSHQIEPA------NREF---CARRNTlelitvrpqred 1077
Cdd:cd13248     19 SGLKNWRKRWFVLKDNCLYY--YKDPEEEK-ALGSILLP---SYTISPAppsdeiSRKFafkAEHANM------------ 80

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1958798354 1078 dretlvsqcrdtlcvTKNWLSADTKEERDLWMQKLNQ 1114
Cdd:cd13248     81 ---------------RTYYFAADTAEEMEQWMNAMSL 102

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958798354 1007 SGFGAWHRRWCVLSGNCISYWTypddeRRKNPIGRI---NLANCISHQIEPANREFCarrntLELITvrPQReddreTLV 1083
Cdd:cd13250     11 NAFKTWKRRWFSLQNGQLYYQK-----RDKKDEPTVmveDLRLCTVKPTEDSDRRFC-----FEVIS--PTK-----SYM 73

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1958798354 1084 sqcrdtlcvtknwLSADTKEERDLWMQKLNQVI 1116
Cdd:cd13250     74 -------------LQAESEEDRQAWIQAIQSAI 93

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        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958798354 1011 AWHRRWCVLSGNCISYWTYPDDerrKNPIGRINLANCishQIEPANRE--FCarrntlelITVRPQREDDReTLVsqcrd 1088
Cdd:cd13288     23 SYQKRWFVLKGNLLFYFEKKGD---REPLGVIVLEGC---TVELAEDAepYA--------FAIRFDGPGAR-SYV----- 82

                           90       100
                   ....*....|....*....|....
gi 1958798354 1089 tlcvtknwLSADTKEERDLWMQKL 1112
Cdd:cd13288     83 --------LAAENQEDMESWMKAL 98

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.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958798354 1012 WHRRWCVLSGNCISYWTYPDDERrknPIGRINLANCISHQIePANREfCARRNTLELItvrPQREDDRETlvsQCRDTlC 1091
Cdd:cd13263     19 WQQRWFVLRGDQLYYYKDEDDTK---PQGTIPLPGNKVKEV-PFNPE-EPGKFLFEII---PGGGGDRMT---SNHDS-Y 86

                           90       100
                   ....*....|....*....|....*
gi 1958798354 1092 VtknwLSADTKEERDLWMQKLNQVI 1116
Cdd:cd13263     87 L----LMANSQAEMEEWVKVIRRVI 107

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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1958798354  998 GFLTIFEDVSGFgaWHRRWCVLSGNCISYwtYPDDERRKNPIGRINLANCISHQIEPAN----REFC 1060
Cdd:cd13215     25 GYLSKRSKRTLR--YTRYWFVLKGDTLSW--YNSSTDLYFPAGTIDLRYATSIELSKSNgeatTSFK 87

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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958798354 1012 WHRRWCVLSGNCISYWTYPDDERRKNPIGRINLANCIShqIEPANREFcARRNTLELITVRpqreddretlvsqcrdtlc 1091
Cdd:cd13276     15 WRRRWFVLKQGKLFWFKEPDVTPYSKPRGVIDLSKCLT--VKSAEDAT-NKENAFELSTPE------------------- 72

                           90       100
                   ....*....|....*....|....*.
gi 1958798354 1092 vTKNWLSADTKEERDLWMQKLNQVIV 1117
Cdd:cd13276     73 -ETFYFIADNEKEKEEWIGAIGRAIV 97

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.

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958798354 1012 WHRRWCVLSGN-CISYWtypDDERRKNPIGRINL-ANCIshqiepanrefcARRNTLELITVRPQREDDRETLVS-QCRD 1088
Cdd:cd13265     19 WKKNWFVLYGDgNLVYY---EDETRREVEGRINMpRECR------------NIRVGLECRDVQPPEGRSRDCLLQiVLRD 83

                           90       100
                   ....*....|....*....|....*....
gi 1958798354 1089 tlcvTKNW-LSADTKEERDLWMQKLNQVI 1116
Cdd:cd13265     84 ----GSTLfLCAESADDALAWKLALQDAR 108

DNA polymerase III subunits gamma and tau; Provisional

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                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1958798354   92 AAKPCSPKPAPRQMKPPAPAAISDSVAAPASLLSTGKASTTSSVKTRMQKLAEQRRH-WDSEITDDVSESSHFSPMPSEE 170
Cdd:PRK14951   390 AAAPVAQAAAAPAPAAAPAAAASAPAAPPAAAPPAPVAAPAAAAPAAAPAAAPAAVAlAPAPPAQAAPETVAIPVRVAPE 469

                           90       100
                   ....*....|....*....|....
gi 1958798354  171 KPASPSKPPVSNASATPVGRRGRL 194
Cdd:PRK14951   470 PAVASAAPAPAAAPAAARLTPTEE 493