Dynamin central region; This is the stalk region which lies between the GTPase domain, see pfam00350, and the pleckstrin homology (PH) domain, see pfam00169. This region dimerizes in a cross-like fashion forming a dynamin dimer in which the two G-domains are oriented in opposite directions.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 817051557  216 DARDILENKLLPLRRGYIGVVNRSQKDIEGRKDIKNALAAERKFFLSHPSYRHLADRLGTPYLQRVLNQQLTNHIRDTLP 295
Cdd:pfam01031   1 DALDILRNRVIPLKLGYVGVVNRSQKDINGNKSIEEALQDERAFFETHPAYRLLADKCGTPYLAKKLNQILVNHIRKSLP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 817051557  296 ALRDRLQKQLLTLEKDVEQYKHFRPDDPAIKTKAMLQMIQQLQSDFERTIEGSgsAQINTNELSGGAKINRLFHERFPFE 375
Cdd:pfam01031  81 DLKNKINELLQKTEKELEKYGNGIPSDPAEKGKFLLQLITKFNQDFKNLIDGE--SEISTNELSGGARIRYIFNEIFPKS 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 817051557  376 IVKMEFDEKELRREIAFAIRNIHGIRVGLFTPDMAFEAIVKKQINRLKEPSLKCVDLVVQELSNVVRICTDRMARYPRLR 455
Cdd:pfam01031 159 LEKIDPLENLSDEEIRTAIRNSRGIRLPLFVPEKAFELLVKQQIKRLEEPALKCVELVYEELERIIHKCTPELKRFPNLR 238

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|...
gi 817051557  456 EETERIITTHVRQREQLCKEQLVLLVDCELAYMNTNHEDFIGF 498
Cdd:pfam01031 239 ERIKEVVEDLLRERLEPTEKMIRSLIEMELAYINTNHPDFIGG 281

Dynamin GTPase effector domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 817051557   666 QLERQVETIRNLVDSYMKIVTKTTRDLVPKAIMMLIINNAKDFINGELLAHLYASGDQSSMMEESPEEAQKREEMLRMYH 745
Cdd:smart00302   1 YEDSELEEIKSLVKSYFTIVSKTLADQVPKAIMYLLVNESKDSLQNELLALLYKEELLDELLEEDPEIASKRKELKKRLE 80

                           90
                   ....*....|..
gi 817051557   746 ACREALRIIGDV 757
Cdd:smart00302  81 LLKKARQIIAAV 92

Dynamin_like protein family includes dynamins and Mx proteins; The dynamin family of large mechanochemical GTPases includes the classical dynamins and dynamin-like proteins (DLPs) that are found throughout the Eukarya. These proteins catalyze membrane fission during clathrin-mediated endocytosis. Dynamin consists of five domains; an N-terminal G domain that binds and hydrolyzes GTP, a middle domain (MD) involved in self-assembly and oligomerization, a pleckstrin homology (PH) domain responsible for interactions with the plasma membrane, GED, which is also involved in self-assembly, and a proline arginine rich domain (PRD) that interacts with SH3 domains on accessory proteins. To date, three vertebrate dynamin genes have been identified; dynamin 1, which is brain specific, mediates uptake of synaptic vesicles in presynaptic terminals; dynamin-2 is expressed ubiquitously and similarly participates in membrane fission; mutations in the MD, PH and GED domains of dynamin 2 have been linked to human diseases such as Charcot-Marie-Tooth peripheral neuropathy and rare forms of centronuclear myopathy. Dynamin 3 participates in megakaryocyte progenitor amplification, and is also involved in cytoplasmic enlargement and the formation of the demarcation membrane system. This family also includes interferon-induced Mx proteins that inhibit a wide range of viruses by blocking an early stage of the replication cycle. Dynamin oligomerizes into helical structures around the neck of budding vesicles in a GTP hydrolysis-dependent manner.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 817051557  30 LDLPQIAVVGGQSAGKSSVLENFVGRDFLPRGSGIVTRRPLILQLINSST--------EHAEFLHQKGKKFVDFDEVRKE 101
Cdd:cd08771    1 IDLPQIVVVGDQSSGKSSVLEALVGRDFLPRGSGICTRRPLELQLRRSPSesdedekeEWGEFLHLKSKEFTDFEELREE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 817051557 102 IEAETDRVTGSNKGISNIPINLRVYSPNVLNLTLIDLPGLTKVPIGDQPVDIEAQIKGMIFQFIKRDNCLILAVTPANTD 181
Cdd:cd08771   81 IEKETDRVAGENKGISPEPIRLEIESPDVPNLTLVDLPGLIKVPVGDQPEDIEEQIRSMVKSYISNPRSIILAVVPANVD 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 817051557 182 LANSDALKLAKEVDPQGVRTIGVITKLDLMDEGTDARDIL---ENKLLPLRRGYIGVVNRSQKDIEGRKDIKNALAAERK 258
Cdd:cd08771  161 LANSEALKLAREVDPEGERTIGVLTKLDLMDPGTDAEDILlllQGKVIPLKLGYVGVVNRSQKDIDSGKSIEEALEAEEE 240

                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 817051557 259 FFLSHPSYRHL-ADRLGTPYLQRVLNQQLTNHIRDTLP 295
Cdd:cd08771  241 FFETHPWYKLLpASRVGTPALRKRLSKLLQKHIRESLP 278

Dynamin pleckstrin homology (PH) domain; Dynamin is a GTPase that regulates endocytic vesicle formation. It has an N-terminal GTPase domain, followed by a PH domain, a GTPase effector domain and a C-terminal proline arginine rich domain. Dynamin-like proteins, which are found in metazoa, plants and yeast have the same domain architecture as dynamin, but lack the 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 817051557 527 NQVIRKGYMCIHNLGIMKGGSRDYWFVLTSESISWFKDEEEREKKYMLPLDGLKLRDLEQGFMSRRHLFALFNPEGRNVY 606
Cdd:cd01256    1 NQVIRKGWLTINNIGFMKGGSKEYWFVLTAESLSWYKDEEEKEKKYMLPLDGLKLRDVEKGFMSRKHIFALFNTDQRNVY 80

                         90       100       110
                 ....*....|....*....|....*....|..
gi 817051557 607 KDYKQLELSCETQDDVDSWKASFLRAGVYPEK 638
Cdd:cd01256   81 KDYKQLELSCETQEEVDSWKASFLRAGVYPEK 112

Dynamin GTPase effector domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 817051557   666 QLERQVETIRNLVDSYMKIVTKTTRDLVPKAIMMLIINNAKDFINGELLAHLYASGDQSSMMEESPEEAQKREEMLRMYH 745
Cdd:smart00302   1 YEDSELEEIKSLVKSYFTIVSKTLADQVPKAIMYLLVNESKDSLQNELLALLYKEELLDELLEEDPEIASKRKELKKRLE 80

                           90
                   ....*....|..
gi 817051557   746 ACREALRIIGDV 757
Cdd:smart00302  81 LLKKARQIIAAV 92

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 817051557   529 VIRKGYMcIHNLGIMKGGSRDYWFVLTSESISWFKDEEEREK---KYMLPLDGLKLRDLEQGF-MSRRHLFALFNPEGRN 604
Cdd:smart00233   1 VIKEGWL-YKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKSykpKGSIDLSGCTVREAPDPDsSKKPHCFEIKTSDRKT 79

                           90       100
                   ....*....|....*....|....*...
gi 817051557   605 VYkdykqleLSCETQDDVDSWKASFLRA 632
Cdd:smart00233  80 LL-------LQAESEEEREKWVEALRKA 100

Dynamin_like protein family includes dynamins and Mx proteins; The dynamin family of large mechanochemical GTPases includes the classical dynamins and dynamin-like proteins (DLPs) that are found throughout the Eukarya. These proteins catalyze membrane fission during clathrin-mediated endocytosis. Dynamin consists of five domains; an N-terminal G domain that binds and hydrolyzes GTP, a middle domain (MD) involved in self-assembly and oligomerization, a pleckstrin homology (PH) domain responsible for interactions with the plasma membrane, GED, which is also involved in self-assembly, and a proline arginine rich domain (PRD) that interacts with SH3 domains on accessory proteins. To date, three vertebrate dynamin genes have been identified; dynamin 1, which is brain specific, mediates uptake of synaptic vesicles in presynaptic terminals; dynamin-2 is expressed ubiquitously and similarly participates in membrane fission; mutations in the MD, PH and GED domains of dynamin 2 have been linked to human diseases such as Charcot-Marie-Tooth peripheral neuropathy and rare forms of centronuclear myopathy. Dynamin 3 participates in megakaryocyte progenitor amplification, and is also involved in cytoplasmic enlargement and the formation of the demarcation membrane system. This family also includes interferon-induced Mx proteins that inhibit a wide range of viruses by blocking an early stage of the replication cycle. Dynamin oligomerizes into helical structures around the neck of budding vesicles in a GTP hydrolysis-dependent manner.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 817051557  30 LDLPQIAVVGGQSAGKSSVLENFVGRDFLPRGSGIVTRRPLILQLINSST--------EHAEFLHQKGKKFVDFDEVRKE 101
Cdd:cd08771    1 IDLPQIVVVGDQSSGKSSVLEALVGRDFLPRGSGICTRRPLELQLRRSPSesdedekeEWGEFLHLKSKEFTDFEELREE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 817051557 102 IEAETDRVTGSNKGISNIPINLRVYSPNVLNLTLIDLPGLTKVPIGDQPVDIEAQIKGMIFQFIKRDNCLILAVTPANTD 181
Cdd:cd08771   81 IEKETDRVAGENKGISPEPIRLEIESPDVPNLTLVDLPGLIKVPVGDQPEDIEEQIRSMVKSYISNPRSIILAVVPANVD 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 817051557 182 LANSDALKLAKEVDPQGVRTIGVITKLDLMDEGTDARDIL---ENKLLPLRRGYIGVVNRSQKDIEGRKDIKNALAAERK 258
Cdd:cd08771  161 LANSEALKLAREVDPEGERTIGVLTKLDLMDPGTDAEDILlllQGKVIPLKLGYVGVVNRSQKDIDSGKSIEEALEAEEE 240

                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 817051557 259 FFLSHPSYRHL-ADRLGTPYLQRVLNQQLTNHIRDTLP 295
Cdd:cd08771  241 FFETHPWYKLLpASRVGTPALRKRLSKLLQKHIRESLP 278

Dynamin pleckstrin homology (PH) domain; Dynamin is a GTPase that regulates endocytic vesicle formation. It has an N-terminal GTPase domain, followed by a PH domain, a GTPase effector domain and a C-terminal proline arginine rich domain. Dynamin-like proteins, which are found in metazoa, plants and yeast have the same domain architecture as dynamin, but lack the 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 817051557 527 NQVIRKGYMCIHNLGIMKGGSRDYWFVLTSESISWFKDEEEREKKYMLPLDGLKLRDLEQGFMSRRHLFALFNPEGRNVY 606
Cdd:cd01256    1 NQVIRKGWLTINNIGFMKGGSKEYWFVLTAESLSWYKDEEEKEKKYMLPLDGLKLRDVEKGFMSRKHIFALFNTDQRNVY 80

                         90       100       110
                 ....*....|....*....|....*....|..
gi 817051557 607 KDYKQLELSCETQDDVDSWKASFLRAGVYPEK 638
Cdd:cd01256   81 KDYKQLELSCETQEEVDSWKASFLRAGVYPEK 112

Dynamin GTPase effector domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 817051557   666 QLERQVETIRNLVDSYMKIVTKTTRDLVPKAIMMLIINNAKDFINGELLAHLYASGDQSSMMEESPEEAQKREEMLRMYH 745
Cdd:smart00302   1 YEDSELEEIKSLVKSYFTIVSKTLADQVPKAIMYLLVNESKDSLQNELLALLYKEELLDELLEEDPEIASKRKELKKRLE 80

                           90
                   ....*....|..
gi 817051557   746 ACREALRIIGDV 757
Cdd:smart00302  81 LLKKARQIIAAV 92

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 817051557   529 VIRKGYMcIHNLGIMKGGSRDYWFVLTSESISWFKDEEEREK---KYMLPLDGLKLRDLEQGF-MSRRHLFALFNPEGRN 604
Cdd:smart00233   1 VIKEGWL-YKKSGGGKKSWKKRYFVLFNSTLLYYKSKKDKKSykpKGSIDLSGCTVREAPDPDsSKKPHCFEIKTSDRKT 79

                           90       100
                   ....*....|....*....|....*...
gi 817051557   605 VYkdykqleLSCETQDDVDSWKASFLRA 632
Cdd:smart00233  80 LL-------LQAESEEEREKWVEALRKA 100

Switch-associated protein-70 Pleckstrin homology (PH) domain; SWAP-70 (also called Differentially expressed in FDCP 6/DEF-6 or IRF4-binding protein) functions in cellular signal transduction pathways (in conjunction with Rac), regulates cell motility through actin rearrangement, and contributes to the transformation and invasion activity of mouse embryo fibroblasts. Metazoan SWAP-70 is found in B lymphocytes, mast cells, and in a variety of organs. Metazoan SWAP-70 contains an N-terminal EF-hand motif, a centrally located PH domain, and a C-terminal coiled-coil domain. The PH domain of Metazoan SWAP-70 contains a phosphoinositide-binding site and a nuclear localization signal (NLS), which localize SWAP-70 to the plasma membrane and nucleus, respectively. The NLS is a sequence of four Lys residues located at the N-terminus of the C-terminal a-helix; this is a unique characteristic of the Metazoan SWAP-70 PH domain. The SWAP-70 PH domain binds PtdIns(3,4,5)P3 and PtdIns(4,5)P2 embedded in lipid bilayer vesicles. There are additional plant SWAP70 proteins, but these are not included in this hierarchy. Rice SWAP70 (OsSWAP70) exhibits GEF activity toward the its Rho GTPase, OsRac1, and regulates chitin-induced production of reactive oxygen species and defense gene expression in rice. Arabidopsis SWAP70 (AtSWAP70) plays a role in both PAMP- and effector-triggered immunity. Plant SWAP70 contains both DH and PH domains, but their arrangement is the reverse of that in typical DH-PH-type Rho GEFs, wherein the DH domain is flanked by a C-terminal PH domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 817051557 523 HTLGNQVIRKGYMcihnlgiMKGGS-----RDYWFVLTSESISWFKDEEEREKKYMLPLDGLKLRDLEQGFMSRRHLFAL 597
Cdd:cd13273    2 DELILDVIKKGYL-------WKKGHllptwTERWFVLKPNSLSYYKSEDLKEKKGEIALDSNCCVESLPDREGKKCRFLV 74

                 ....
gi 817051557 598 FNPE 601
Cdd:cd13273   75 KTPD 78

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 817051557 551 WFVLTSESISWFKDEEEREKKYMLPLDGLKLRDLEQgfMSRRHLFALFNPEGRNVYKDYKQ-------------LELSCE 617
Cdd:cd01252   23 WFILTDNCLYYFEYTTDKEPRGIIPLENLSVREVED--KKKPFCFELYSPSNGQVIKACKTdsdgkvvegnhtvYRISAA 100

                 ....*...
gi 817051557 618 TQDDVDSW 625
Cdd:cd01252  101 SEEERDEW 108

Pleckstrin 2 Pleckstrin homology (PH) domain, repeat 1; Pleckstrin is a protein found in platelets. This name is derived from platelet and leukocyte C kinase substrate and the KSTR string of amino acids. Pleckstrin 2 contains two PH domains and a DEP (dishvelled, egl-10, and pleckstrin) domain. Unlike pleckstrin 1, pleckstrin 2 does not contain obvious sites of PKC phosphorylation. Pleckstrin 2 plays a role in actin rearrangement, large lamellipodia and peripheral ruffle formation, and may help orchestrate cytoskeletal arrangement. The PH domains of pleckstrin 2 are thought to contribute to lamellipodia formation. This cd contains the first PH domain repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 817051557 528 QVIRKGYMcihnlgiMKGGS-----RDYWFVLTSESISWFKDEEEREKKYMLPLDGLKLRDLEQGFMSRRHLFALFNPEG 602
Cdd:cd13301    2 GIIKEGYL-------VKKGHvvnnwKARWFVLKEDGLEYYKKKTDSSPKGMIPLKGCTITSPCLEYGKRPLVFKLTTAKG 74

                         90       100       110
                 ....*....|....*....|....*....|
gi 817051557 603 RNVYkdykqleLSCETQDDVDSWKASFLRA 632
Cdd:cd13301   75 QEHF-------FQACSREERDAWAKDITKA 97

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 817051557 529 VIRKGYMciHNLGimkgGS-----RDYWFVLTSESISWFKDEEEREKKYMLPLDGLKLRDLEQGF-MSRRHLFALFNPEG 602
Cdd:cd13248    7 VVMSGWL--HKQG----GSglknwRKRWFVLKDNCLYYYKDPEEEKALGSILLPSYTISPAPPSDeISRKFAFKAEHANM 80

                         90       100
                 ....*....|....*....|...
gi 817051557 603 RNVYkdykqleLSCETQDDVDSW 625
Cdd:cd13248   81 RTYY-------FAADTAEEMEQW 96