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 24642340   210 DARDILENKLLPLRRGYIGVVNRSQKDIEGRKDIHQALAAERKFFLSHPSYRHMADRLGTPYLQRVLNQQLTNHIRDTLP 289
Cdd:pfam01031   1 DALDILRNRVIPLKLGYVGVVNRSQKDINGNKSIEEALQDERAFFETHPAYRLLADKCGTPYLAKKLNQILVNHIRKSLP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24642340   290 GLRDKLQKQMLTLEKEVEEFKHFQPGDASIKTKAMLQMIQQLQSDFERTIEGSGSalVNTNELSGGAKINRIFHERLRFE 369
Cdd:pfam01031  81 DLKNKINELLQKTEKELEKYGNGIPSDPAEKGKFLLQLITKFNQDFKNLIDGESE--ISTNELSGGARIRYIFNEIFPKS 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24642340   370 IVKMACDEKELRREISFAIRNIHGIRVGLFTPDMAFEAIVKRQIALLKEPVIKCVDLVVQELSVVVRMCTAKMSRYPRLR 449
Cdd:pfam01031 159 LEKIDPLENLSDEEIRTAIRNSRGIRLPLFVPEKAFELLVKQQIKRLEEPALKCVELVYEELERIIHKCTPELKRFPNLR 238

                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*....
gi 24642340   450 EETERIITTHVRQREHSCKEQILLLIDFELAYMNTNHEDFIGFANAQNK 498
Cdd:pfam01031 239 ERIKEVVEDLLRERLEPTEKMIRSLIEMELAYINTNHPDFIGGLNAVRE 287

Dynamin GTPase effector domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24642340    645 QLERQVETIRNLVDSYMKIVTKTTRDMVPKAIMMLIINNAKDFINGELLAHLYASGDQAQMMEESAESATRREEMLRMYR 724
Cdd:smart00302   1 YEDSELEEIKSLVKSYFTIVSKTLADQVPKAIMYLLVNESKDSLQNELLALLYKEELLDELLEEDPEIASKRKELKKRLE 80

                           90
                   ....*....|..
gi 24642340    725 ACKDALQIIGDV 736
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 24642340  24 LDLPQIAVVGGQSAGKSSVLENFVGKDFLPRGSGIVTRRPLILQLING--------VTEYGEFLHIKGKKFSSFDEIRKE 95
Cdd:cd08771   1 IDLPQIVVVGDQSSGKSSVLEALVGRDFLPRGSGICTRRPLELQLRRSpsesdedeKEEWGEFLHLKSKEFTDFEELREE 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24642340  96 IEDETDRVTGSNKGISNIPINLRVYSPHVLNLTLIDLPGLTKVAIGDQPVDIEQQIKQMIFQFIRKETCLILAVTPANTD 175
Cdd:cd08771  81 IEKETDRVAGENKGISPEPIRLEIESPDVPNLTLVDLPGLIKVPVGDQPEDIEEQIRSMVKSYISNPRSIILAVVPANVD 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24642340 176 LANSDALKLAKEVDPQGVRTIGVITKLDLMDEGTDARDIL---ENKLLPLRRGYIGVVNRSQKDIEGRKDIHQALAAERK 252
Cdd:cd08771 161 LANSEALKLAREVDPEGERTIGVLTKLDLMDPGTDAEDILlllQGKVIPLKLGYVGVVNRSQKDIDSGKSIEEALEAEEE 240

                       250       260       270
                ....*....|....*....|....*....|....*...
gi 24642340 253 FFLSHPSYRH-MADRLGTPYLQRVLNQQLTNHIRDTLP 289
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 24642340 512 NQVIRKGHMVIQNLGIMKGGSRPYWFVLTSESISWYKDEDEKEKKFMLPLDGLKLRDIEQGFmsMSRRVTFALFSPDGRN 591
Cdd:cd01256   1 NQVIRKGWLTINNIGFMKGGSKEYWFVLTAESLSWYKDEEEKEKKYMLPLDGLKLRDVEKGF--MSRKHIFALFNTDQRN 78

                        90       100       110
                ....*....|....*....|....*....|....
gi 24642340 592 VYKDYKQLELSCETVEDVESWKASFLRAGVYPEK 625
Cdd:cd01256  79 VYKDYKQLELSCETQEEVDSWKASFLRAGVYPEK 112

Dynamin GTPase effector domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24642340    645 QLERQVETIRNLVDSYMKIVTKTTRDMVPKAIMMLIINNAKDFINGELLAHLYASGDQAQMMEESAESATRREEMLRMYR 724
Cdd:smart00302   1 YEDSELEEIKSLVKSYFTIVSKTLADQVPKAIMYLLVNESKDSLQNELLALLYKEELLDELLEEDPEIASKRKELKKRLE 80

                           90
                   ....*....|..
gi 24642340    725 ACKDALQIIGDV 736
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 24642340    514 VIRKGHMVIQNlGIMKGGSRPYWFVLTSESISWYKDEDEKEK---KFMLPLDGLKLRDIEQGFmSMSRRVTFALFSPDGR 590
Cdd:smart00233   1 VIKEGWLYKKS-GGGKKSWKKRYFVLFNSTLLYYKSKKDKKSykpKGSIDLSGCTVREAPDPD-SSKKPHCFEIKTSDRK 78

                           90       100
                   ....*....|....*....|....*....
gi 24642340    591 NVYkdykqleLSCETVEDVESWKASFLRA 619
Cdd:smart00233  79 TLL-------LQAESEEEREKWVEALRKA 100

Formin Homology Region 1; This region is found in some of the Diaphanous related formins (Drfs). It consists of low complexity repeats of around 12 residues.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24642340   740 TVSSPLPPPvkndwLPSGLDNPRlSPPSPGGVRGKPGPPAQSSLG-GRNPPLPPSTGRPAPAIP 802
Cdd:pfam06346  42 SAAIPPPPP-----LPGGTSIPP-PPPLPGAASIPPPPPLPGSTGiPPPPPLPGGAGIPPPPPP 99

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 24642340  24 LDLPQIAVVGGQSAGKSSVLENFVGKDFLPRGSGIVTRRPLILQLING--------VTEYGEFLHIKGKKFSSFDEIRKE 95
Cdd:cd08771   1 IDLPQIVVVGDQSSGKSSVLEALVGRDFLPRGSGICTRRPLELQLRRSpsesdedeKEEWGEFLHLKSKEFTDFEELREE 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24642340  96 IEDETDRVTGSNKGISNIPINLRVYSPHVLNLTLIDLPGLTKVAIGDQPVDIEQQIKQMIFQFIRKETCLILAVTPANTD 175
Cdd:cd08771  81 IEKETDRVAGENKGISPEPIRLEIESPDVPNLTLVDLPGLIKVPVGDQPEDIEEQIRSMVKSYISNPRSIILAVVPANVD 160

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24642340 176 LANSDALKLAKEVDPQGVRTIGVITKLDLMDEGTDARDIL---ENKLLPLRRGYIGVVNRSQKDIEGRKDIHQALAAERK 252
Cdd:cd08771 161 LANSEALKLAREVDPEGERTIGVLTKLDLMDPGTDAEDILlllQGKVIPLKLGYVGVVNRSQKDIDSGKSIEEALEAEEE 240

                       250       260       270
                ....*....|....*....|....*....|....*...
gi 24642340 253 FFLSHPSYRH-MADRLGTPYLQRVLNQQLTNHIRDTLP 289
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 24642340 512 NQVIRKGHMVIQNLGIMKGGSRPYWFVLTSESISWYKDEDEKEKKFMLPLDGLKLRDIEQGFmsMSRRVTFALFSPDGRN 591
Cdd:cd01256   1 NQVIRKGWLTINNIGFMKGGSKEYWFVLTAESLSWYKDEEEKEKKYMLPLDGLKLRDVEKGF--MSRKHIFALFNTDQRN 78

                        90       100       110
                ....*....|....*....|....*....|....
gi 24642340 592 VYKDYKQLELSCETVEDVESWKASFLRAGVYPEK 625
Cdd:cd01256  79 VYKDYKQLELSCETQEEVDSWKASFLRAGVYPEK 112

Dynamin GTPase effector domain;

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24642340    645 QLERQVETIRNLVDSYMKIVTKTTRDMVPKAIMMLIINNAKDFINGELLAHLYASGDQAQMMEESAESATRREEMLRMYR 724
Cdd:smart00302   1 YEDSELEEIKSLVKSYFTIVSKTLADQVPKAIMYLLVNESKDSLQNELLALLYKEELLDELLEEDPEIASKRKELKKRLE 80

                           90
                   ....*....|..
gi 24642340    725 ACKDALQIIGDV 736
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 24642340    514 VIRKGHMVIQNlGIMKGGSRPYWFVLTSESISWYKDEDEKEK---KFMLPLDGLKLRDIEQGFmSMSRRVTFALFSPDGR 590
Cdd:smart00233   1 VIKEGWLYKKS-GGGKKSWKKRYFVLFNSTLLYYKSKKDKKSykpKGSIDLSGCTVREAPDPD-SSKKPHCFEIKTSDRK 78

                           90       100
                   ....*....|....*....|....*....
gi 24642340    591 NVYkdykqleLSCETVEDVESWKASFLRA 619
Cdd:smart00233  79 TLL-------LQAESEEEREKWVEALRKA 100

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

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24642340 516 RKGHMVIQNLGIMKGGSRpYWFVLTSESISWYKDEDE--KEKKFMLPLDG-LKLRDIEQGfmsmSRRVTFALFSPDGRNV 592
Cdd:cd00821   1 KEGYLLKRGGGGLKSWKK-RWFVLFEGVLLYYKSKKDssYKPKGSIPLSGiLEVEEVSPK----ERPHCFELVTPDGRTY 75

                        90       100
                ....*....|....*....|
gi 24642340 593 YkdykqleLSCETVEDVESW 612
Cdd:cd00821  76 Y-------LQADSEEERQEW 88

Fungal proteins Pleckstrin homology (PH) domain, repeat 1; The functions of these fungal proteins are unknown, but they all contain 2 PH domains. This cd represents the first PH repeat. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 24642340 533 RPYWFVLTSESISWYKDEDEKEKKFMLPLDGL----KLRDIEQGFmsmsrrvTFALFSPDgrnvykdyKQLELSCETVED 608
Cdd:cd13298  23 KKRWVVLRPCQLSYYKDEKEYKLRRVINLSELlavaPLKDKKRKN-------VFGIYTPS--------KNLHFRATSEKD 87

                ....
gi 24642340 609 VESW 612
Cdd:cd13298  88 ANEW 91

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
                ....*....|....*....|....*....|....*....|....*....|....
gi 24642340 513 QVIRKGHMVIQnlGIMKGGSRPYWFVLTSESISWYKDEDEKEKKFMLPLDGLKL 566
Cdd:cd13301   2 GIIKEGYLVKK--GHVVNNWKARWFVLKEDGLEYYKKKTDSSPKGMIPLKGCTI 53

Formin Homology Region 1; This region is found in some of the Diaphanous related formins (Drfs). It consists of low complexity repeats of around 12 residues.

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 24642340   740 TVSSPLPPPvkndwLPSGLDNPRlSPPSPGGVRGKPGPPAQSSLG-GRNPPLPPSTGRPAPAIP 802
Cdd:pfam06346  42 SAAIPPPPP-----LPGGTSIPP-PPPLPGAASIPPPPPLPGSTGiPPPPPLPGGAGIPPPPPP 99

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
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 24642340 536 WFVLTSESISWYKDEDEKEKKFMLPLDGLKLRDIeQGFMSMSRRVTFALFSPDGRNVYkdykqleLSCETVEDVESW 612
Cdd:cd13248  28 WFVLKDNCLYYYKDPEEEKALGSILLPSYTISPA-PPSDEISRKFAFKAEHANMRTYY-------FAADTAEEMEQW 96