Cell division protein anillin; Anillin is a protein involved in septin organization during cell division. It is an actin binding protein that is localized to the cleavage furrow, and it maintains the localization of active myosin, which ensures the spatial control of concerted contraction during cytokinesis.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742   835 SKGSISLLELRLPLKADFICSSANKPECGNHYFFVMIRAGpENTVATPLSSTRTGLSGDALTFTTTFTLSDVSNDFEIDI 914
Cdd:pfam08174    1 CKGKVTISDIRIPLKWRFVDHFKNKGESRRYAFFCLLKCG-TEIEATDLVSTLDRTDGTDICFGDPITFSNVPPDFEITV 79

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 255069742   915 EVYCLVQKRELNPdkrkkasksKAITPKRFL-NISKSnlqtPVMASPGGPNAV-RTSSFVLVGSHKLTLASIG 985
Cdd:pfam08174   80 EVYSLRVTEEKLS---------SALTPKKLAsKLASK----SLGRSPGGKLAVrRGSKFKLLGSLTLTLLSVG 139

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742    2 DPFTEKLLERTRARRENLQKKMAERPTAANRPMAKRTREPLTDtnsvLSEPTIEKALPSSKPSPFkrrCSDENTFLAGEE 81
Cdd:PHA03247 2655 DPAPGRVSRPRRARRLGRAAQASSPPQRPRRRAARPTVGSLTS----LADPPPPPPTPEPAPHAL---VSATPLPPGPAA 2727

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742   82 NKQPVAPQMTDPMTdqkPPLAPTTVRPIPVEQRSAPDmLPTRPPPETekmvvcPPQSPAKrtdnvlrqkgldgaretqKE 161
Cdd:PHA03247 2728 ARQASPALPAAPAP---PAVPAGPATPGGPARPARPP-TTAGPPAPA------PPAAPAA------------------GP 2779

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742  162 APTTFPSSMRSRLQRLAGQRQNWDSNGATEAVS-ESVVVSPLKSHNLDHPPATPTNSEVPVGRKGRLANLAATIGSWEDd 240
Cdd:PHA03247 2780 PRRLTRPAVASLSESRESLPSPWDPADPPAAVLaPAAALPPAASPAGPLPPPTSAQPTAPPPPPGPPPPSLPLGGSVAP- 2858

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742  241 lGHPPIRRDNAqaqpgtayvRPPVSTVTSnseqlqSARPtshrPVNRGQQPAVYSPVKSTSVVPPSPQKTEFPQA----- 315
Cdd:PHA03247 2859 -GGDVRRRPPS---------RSPAAKPAA------PARP----PVRRLARPAVSRSTESFALPPDQPERPPQPQAppppq 2918

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742  316 --RWAQAVPSPVSSPlkiPPSTQPSSPLKSVTASPSSPHRGYVSQSPLKSHGQVDKLNFGAALNSSPAKPVLAPKPSAA- 392
Cdd:PHA03247 2919 pqPQPPPPPQPQPPP---PPPPRPQPPLAPTTDPAGAGEPSGAVPQPWLGALVPGRVAVPRFRVPQPAPSREAPASSTPp 2995

                  ....*....
gi 255069742  393 --DDAVSRV 399
Cdd:PHA03247 2996 ltGHSLSRV 3004

Cell division protein anillin; Anillin is a protein involved in septin organization during cell division. It is an actin binding protein that is localized to the cleavage furrow, and it maintains the localization of active myosin, which ensures the spatial control of concerted contraction during cytokinesis.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742   835 SKGSISLLELRLPLKADFICSSANKPECGNHYFFVMIRAGpENTVATPLSSTRTGLSGDALTFTTTFTLSDVSNDFEIDI 914
Cdd:pfam08174    1 CKGKVTISDIRIPLKWRFVDHFKNKGESRRYAFFCLLKCG-TEIEATDLVSTLDRTDGTDICFGDPITFSNVPPDFEITV 79

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 255069742   915 EVYCLVQKRELNPdkrkkasksKAITPKRFL-NISKSnlqtPVMASPGGPNAV-RTSSFVLVGSHKLTLASIG 985
Cdd:pfam08174   80 EVYSLRVTEEKLS---------SALTPKKLAsKLASK----SLGRSPGGKLAVrRGSKFKLLGSLTLTLLSVG 139

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.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742   1019 KGFLTMFEDvSGFGAWHRRWCVLSGYCISYWTYPDDEKRKNPMGRINLANCTSRkvEPANREFCARPNTFELITvrpqre 1098
Cdd:smart00233    4 EGWLYKKSG-GGKKSWKKRYFVLFNSTLLYYKSKKDKKSYKPKGSIDLSGCTVR--EAPDPDSSKKPHCFEIKT------ 74

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|
gi 255069742   1099 DDRETLVsrckdtlcvtknwLSADTKDERNLWMQKLNQIL 1138
Cdd:smart00233   75 SDRKTLL-------------LQAESEEEREKWVEALRKAI 101

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742    2 DPFTEKLLERTRARRENLQKKMAERPTAANRPMAKRTREPLTDtnsvLSEPTIEKALPSSKPSPFkrrCSDENTFLAGEE 81
Cdd:PHA03247 2655 DPAPGRVSRPRRARRLGRAAQASSPPQRPRRRAARPTVGSLTS----LADPPPPPPTPEPAPHAL---VSATPLPPGPAA 2727

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742   82 NKQPVAPQMTDPMTdqkPPLAPTTVRPIPVEQRSAPDmLPTRPPPETekmvvcPPQSPAKrtdnvlrqkgldgaretqKE 161
Cdd:PHA03247 2728 ARQASPALPAAPAP---PAVPAGPATPGGPARPARPP-TTAGPPAPA------PPAAPAA------------------GP 2779

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742  162 APTTFPSSMRSRLQRLAGQRQNWDSNGATEAVS-ESVVVSPLKSHNLDHPPATPTNSEVPVGRKGRLANLAATIGSWEDd 240
Cdd:PHA03247 2780 PRRLTRPAVASLSESRESLPSPWDPADPPAAVLaPAAALPPAASPAGPLPPPTSAQPTAPPPPPGPPPPSLPLGGSVAP- 2858

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742  241 lGHPPIRRDNAqaqpgtayvRPPVSTVTSnseqlqSARPtshrPVNRGQQPAVYSPVKSTSVVPPSPQKTEFPQA----- 315
Cdd:PHA03247 2859 -GGDVRRRPPS---------RSPAAKPAA------PARP----PVRRLARPAVSRSTESFALPPDQPERPPQPQAppppq 2918

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742  316 --RWAQAVPSPVSSPlkiPPSTQPSSPLKSVTASPSSPHRGYVSQSPLKSHGQVDKLNFGAALNSSPAKPVLAPKPSAA- 392
Cdd:PHA03247 2919 pqPQPPPPPQPQPPP---PPPPRPQPPLAPTTDPAGAGEPSGAVPQPWLGALVPGRVAVPRFRVPQPAPSREAPASSTPp 2995

                  ....*....
gi 255069742  393 --DDAVSRV 399
Cdd:PHA03247 2996 ltGHSLSRV 3004

Cell division protein anillin; Anillin is a protein involved in septin organization during cell division. It is an actin binding protein that is localized to the cleavage furrow, and it maintains the localization of active myosin, which ensures the spatial control of concerted contraction during cytokinesis.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742   835 SKGSISLLELRLPLKADFICSSANKPECGNHYFFVMIRAGpENTVATPLSSTRTGLSGDALTFTTTFTLSDVSNDFEIDI 914
Cdd:pfam08174    1 CKGKVTISDIRIPLKWRFVDHFKNKGESRRYAFFCLLKCG-TEIEATDLVSTLDRTDGTDICFGDPITFSNVPPDFEITV 79

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 255069742   915 EVYCLVQKRELNPdkrkkasksKAITPKRFL-NISKSnlqtPVMASPGGPNAV-RTSSFVLVGSHKLTLASIG 985
Cdd:pfam08174   80 EVYSLRVTEEKLS---------SALTPKKLAsKLASK----SLGRSPGGKLAVrRGSKFKLLGSLTLTLLSVG 139

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.

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742   1019 KGFLTMFEDvSGFGAWHRRWCVLSGYCISYWTYPDDEKRKNPMGRINLANCTSRkvEPANREFCARPNTFELITvrpqre 1098
Cdd:smart00233    4 EGWLYKKSG-GGKKSWKKRYFVLFNSTLLYYKSKKDKKSYKPKGSIDLSGCTVR--EAPDPDSSKKPHCFEIKT------ 74

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|
gi 255069742   1099 DDRETLVsrckdtlcvtknwLSADTKDERNLWMQKLNQIL 1138
Cdd:smart00233   75 SDRKTLL-------------LQAESEEEREKWVEALRKAI 101

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 255069742 1034 WHRRWCVLSGYCISYWTYPDDekrKNPMGRINLANCTSRKVEPANREFCarpntFELITvrpqreDDRETLVSRCK---D 1110
Cdd:cd01252    19 WKRRWFILTDNCLYYFEYTTD---KEPRGIIPLENLSVREVEDKKKPFC-----FELYS------PSNGQVIKACKtdsD 84

                          90       100       110
                  ....*....|....*....|....*....|
gi 255069742 1111 TLCVTKN----WLSADTKDERNLWMQKLNQ 1136
Cdd:cd01252    85 GKVVEGNhtvyRISAASEEERDEWIKSIKA 114

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 255069742 1029 SGFGAWHRRWCVLSGYCISYWTYPDDEKrknPMGRINLANCTSRKVEPANRefCARPNTFELitvrpQREDDRetlvsrc 1108
Cdd:cd13248    19 SGLKNWRKRWFVLKDNCLYYYKDPEEEK---ALGSILLPSYTISPAPPSDE--ISRKFAFKA-----EHANMR------- 81

                          90       100
                  ....*....|....*....|....*...
gi 255069742 1109 kdtlcvtKNWLSADTKDERNLWMQKLNQ 1136
Cdd:cd13248    82 -------TYYFAADTAEEMEQWMNAMSL 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 255069742 1029 SGFGAWHRRWCVLSGYCISYwtYPDDEKRKNPMGRINLANCTSRKVEPANREFCarpntFELITvrPQReddreTLVsrc 1108
Cdd:cd13250    11 NAFKTWKRRWFSLQNGQLYY--QKRDKKDEPTVMVEDLRLCTVKPTEDSDRRFC-----FEVIS--PTK-----SYM--- 73

                          90       100
                  ....*....|....*....|....*..
gi 255069742 1109 kdtlcvtknwLSADTKDERNLWMQKLN 1135
Cdd:cd13250    74 ----------LQAESEEDRQAWIQAIQ 90

large tegument protein UL36; Provisional

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742   52 PTIEKALPSSKPSPfkrrcsdentflageenkQPVAPQMTDpmTDQKPPLAPTTVRP-IPVEQR-SAPDMLPTRPPPETE 129
Cdd:PHA03247 2562 AAPDRSVPPPRPAP------------------RPSEPAVTS--RARRPDAPPQSARPrAPVDDRgDPRGPAPPSPLPPDT 2621

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742  130 KMVVCPPQSPAKRTDNVlrqKGLDGARETQKEAPTTFPSSMRSRLQRLAGQR----------QNWDSNGATEAV-SESVV 198
Cdd:PHA03247 2622 HAPDPPPPSPSPAANEP---DPHPPPTVPPPERPRDDPAPGRVSRPRRARRLgraaqassppQRPRRRAARPTVgSLTSL 2698

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742  199 VSPLKSHNLDHPPATPTNSEVPvgrkgrlanlaATIGSWEDDLGHPPIRRDNAQAQPGTAYVrPPVSTVTSNSEQLQSAR 278
Cdd:PHA03247 2699 ADPPPPPPTPEPAPHALVSATP-----------LPPGPAAARQASPALPAAPAPPAVPAGPA-TPGGPARPARPPTTAGP 2766

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742  279 PTSHRPVNRGQQPAVYSPVksTSVVPPSPQKTEFPQARWAQAVPSPVSSPLK-IPPSTQPSSPL---KSVTASPSSPHRG 354
Cdd:PHA03247 2767 PAPAPPAAPAAGPPRRLTR--PAVASLSESRESLPSPWDPADPPAAVLAPAAaLPPAASPAGPLpppTSAQPTAPPPPPG 2844

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|
gi 255069742  355 YVsQSPLKSHGQV---DKLNFGAALNSSPAKPVLAPKPSA---ADDAVSR 398
Cdd:PHA03247 2845 PP-PPSLPLGGSVapgGDVRRRPPSRSPAAKPAAPARPPVrrlARPAVSR 2893

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 255069742 1019 KGFLTMFEDVSGFGAWHRRWCVLSG---YCisYWTYPDDEKRKNPMGRINLANCTsrKVEPANREFCARPNTFELITVRP 1095
Cdd:cd13249     5 SGYLSQQQSVEGLQSWTRLYCVLKGgnlLC--YYSPEEIEAKVEPLLTIPINKET--RIRAVEKDSKGRASSLSIINPYS 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 255069742 1096 qreDDRETLVsrckdtlcvtknwLSADTKDERNLWMQKLNQILVDL 1141
Cdd:cd13249    81 ---GEEVTHV-------------LSADSREELQKWMEALWQHFYDM 110

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742 1019 KGFLtMFEDVSGfGAWHRRWCVLSGYCISYWTYPDDEKRKNPMGRINLANCTSRKVEPANREFcarpnTFELITvrpqRE 1098
Cdd:cd13275     2 KGWL-MKQGSRQ-GEWSKHWFVLRGAALKYYRDPSAEEAGELDGVIDLSSCTEVTELPVSRNY-----GFQVKT----WD 70

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 255069742 1099 DDRETlvsrckdtlcvtknwLSADTKDERNLWMQKLNQ 1136
Cdd:cd13275    71 GKVYV---------------LSAMTSGIRTNWIQALRK 93

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 255069742 1020 GFLTmfeDVSG-FGAWHRRWCVLSGYCISYWTYPDDEKRKnPMGRINLAncTSRKVEPANREfcarpNTFELIT 1092
Cdd:cd13282     3 GYLT---KLGGkVKTWKRRWFVLKNGELFYYKSPNDVIRK-PQGQIALD--GSCEIARAEGA-----QTFEIVT 65

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.

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 255069742 1020 GFLTMFEDVSGFgaWHRRWCVLSGYCISYwtYPDDEKRKNPMGRINLANCTSRKVEPANREfcaRPNTFELIT 1092
Cdd:cd13215    25 GYLSKRSKRTLR--YTRYWFVLKGDTLSW--YNSSTDLYFPAGTIDLRYATSIELSKSNGE---ATTSFKIVT 90

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 255069742 1034 WHRRWCVLSGYCISYWTYPDDEKrknPMGRINLANCTSRKVePANREfcaRPN--TFELItvrPQREDDRETlvsRCKDT 1111
Cdd:cd13263    19 WQQRWFVLRGDQLYYYKDEDDTK---PQGTIPLPGNKVKEV-PFNPE---EPGkfLFEII---PGGGGDRMT---SNHDS 85

                          90       100
                  ....*....|....*....|....*..
gi 255069742 1112 lCVtknwLSADTKDERNLWMQKLNQIL 1138
Cdd:cd13263    86 -YL----LMANSQAEMEEWVKVIRRVI 107

Atrophin-1 family; Atrophin-1 is the protein product of the dentatorubral-pallidoluysian atrophy (DRPLA) gene. DRPLA OMIM:125370 is a progressive neurodegenerative disorder. It is caused by the expansion of a CAG repeat in the DRPLA gene on chromosome 12p. This results in an extended polyglutamine region in atrophin-1, that is thought to confer toxicity to the protein, possibly through altering its interactions with other proteins. The expansion of a CAG repeat is also the underlying defect in six other neurodegenerative disorders, including Huntington's disease. One interaction of expanded polyglutamine repeats that is thought to be pathogenic is that with the short glutamine repeat in the transcriptional coactivator CREB binding protein, CBP. This interaction draws CBP away from its usual nuclear location to the expanded polyglutamine repeat protein aggregates that are characteriztic of the polyglutamine neurodegenerative disorders. This interferes with CBP-mediated transcription and causes cytotoxicity.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742    27 PTAANRPMAKRTREPLTDTNSVLSEPTIEKALPSSKPSPfkrRCSDENTFLAGEENKQPVAPQMTDPMTDQKPPLAPTTV 106
Cdd:pfam03154  185 SPPPPGTTQAATAGPTPSAPSVPPQGSPATSQPPNQTQS---TAAPHTLIQQTPTLHPQRLPSPHPPLQPMTQPPPPSQV 261

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742   107 RPIPVEQRSapdmLPTRPPPETEKMVVCPPQSPAKRTDNVLRQKGLDGARETQKEAPTTFPSSMRSRLQRLAGQRQNWDS 186
Cdd:pfam03154  262 SPQPLPQPS----LHGQMPPMPHSLQTGPSHMQHPVPPQPFPLTPQSSQSQVPPGPSPAAPGQSQQRIHTPPSQSQLQSQ 337

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742   187 NGATEavsESVVVSPLKSHNLDHPPATPTNS-EVPVGRKGRLANLAATIGSWEDDLGHPPIRR---DNAQAQPGTAYvrP 262
Cdd:pfam03154  338 QPPRE---QPLPPAPLSMPHIKPPPTTPIPQlPNPQSHKHPPHLSGPSPFQMNSNLPPPPALKplsSLSTHHPPSAH--P 412

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742   263 PVSTVTSNSEQLQSarPTSHRPVNRGQQ--PAVYSPVKSTSVVPPSPQKTEFPQARWAQAVPSPVSSPLKIPPSTQPS-- 338
Cdd:pfam03154  413 PPLQLMPQSQQLPP--PPAQPPVLTQSQslPPPAASHPPTSGLHQVPSQSPFPQHPFVPGGPPPITPPSGPPTSTSSAmp 490

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|...
gi 255069742   339 --SPLKSVTASPSSPHRGYVSQSPLKSHGQVDKLNfGAALNSSPAKPVLAPKP 389
Cdd:pfam03154  491 giQPPSSASVSSSGPVPAAVSCPLPPVQIKEEALD-EAEEPESPPPPPRSPSP 542

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742 1034 WHRRWCVLSGYCISYWTypdDEKRKNPMGRINLANCTSRKVEPANRefcARPNTFELITVRPqreddretlvsrCKDTlc 1113
Cdd:cd13308    28 WQLRYVIIHQGCVYYYK---NDQSAKPKGVFSLNGYNRRAAEERTS---KLKFVFKIIHLSP------------DHRT-- 87

                          90       100
                  ....*....|....*....|...
gi 255069742 1114 vtknW-LSADTKDERNLWMQKLN 1135
Cdd:cd13308    88 ----WyFAAKSEDEMSEWMEYIR 106

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742 1019 KGFLTMFEDV-SGFGAwhrRWCVLSGYCISYWTYPDDEKrKNPMGRINLANCtsrKVEPANREfcarPNTFELITvrpqr 1097
Cdd:cd13292     5 KGYLKKWTNYaKGYKT---RWFVLEDGVLSYYRHQDDEG-SACRGSINMKNA---RLVSDPSE----KLRFEVSS----- 68

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 255069742 1098 eddretlvsrckDTLCVTKNWLSADTKDERNLWMQKLNQ 1136
Cdd:cd13292    69 ------------KTSGSPKWYLKANHPVEAARWIQALQK 95

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.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 255069742 1034 WHRRWCVLSGY-CISYWtypDDEKRKNPMGRINL-ANCTSRKVEPANREfcarpntfelitVRPQREDDRETLVS-RCKD 1110
Cdd:cd13265    19 WKKNWFVLYGDgNLVYY---EDETRREVEGRINMpRECRNIRVGLECRD------------VQPPEGRSRDCLLQiVLRD 83

                          90       100
                  ....*....|....*....|....*..
gi 255069742 1111 tlcvTKNW-LSADTKDERNLWMQKLNQ 1136
Cdd:cd13265    84 ----GSTLfLCAESADDALAWKLALQD 106