Breakpoint Cluster Region-related pleckstrin homology (PH) domain; The BCR gene is one of the two genes in the BCR-ABL complex, which is associated with the Philadelphia chromosome, a product of a reciprocal translocation between chromosomes 22 and 9. BCR is a GTPase-activating protein (GAP) for RAC1 (primarily) and CDC42. The Dbl region of BCR has the most RhoGEF activity for Cdc42, and less activity towards Rac and Rho. Since BCR possesses both GAP and GEF activities, it may function to temporally regulate the activity of these GTPases. It also displays serine/threonine kinase activity. The BCR protein contains multiple domains including an N-terminal kinase domain, a RhoGEF domain, a PH domain, a C1 domain, a C2 domain, and a C-terminal RhoGAP domain. This hierarchy is composed of arthropod BCRs. 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 281359606 542 MFLNQFNVVNQRLPIESNRNLRRMVRNSFIVELVDGHRKLRHLFLFNDVIACAKYKALGRDRIDYELKWFIPLKDVSIYE 621
Cdd:cd13368    1 FLNEFNNIQTKSMFPHQDRALRRLVKNSFIVELADGHRKLRHLFLFNDVIACAKYKSSGRTRITFELKWFIPLNDVTILE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281359606 622 EADPAVelKESSPANISQVKRNLRSVRDQLAMEVANSGSGAfrsgDKYRRKLADLESQLVLATPNLVLRLGNKaNNKTIT 701
Cdd:cd13368   81 EEAPAP--KESSPPNIEQLKSNACQVRDQLADRSRASTSGS----DKIRKKLADLEAQLVLASPNLVFRIGNK-NNKTYT 153

                        170       180
                 ....*....|....*....|....*..
gi 281359606 702 FFLSSDFERTQWIDSILSLKQKCNLPG 728
Cdd:cd13368  154 FFLSSEFERTQWIEAILTLQQTCPLPG 180

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281359606 770 LYMGVHGLEGLEQANDLYICVEVDSYGHYFRKATTkKICRSQT-PLWNESFMLELEGSQNVRILLYE-----------AK 837
Cdd:cd08686    1 LNVIVHSAQGFKQSANLYCTLEVDSFGYFVKKAKT-RVCRDTTePNWNEEFEIELEGSQTLRILCYEkcyskvkldgeGT 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 281359606 838 ERPLLKAKHILKLSLSWLTEtTQPKSIKLTEtLELGCSFRF 878
Cdd:cd08686   80 DAIMGKGQIQLDPQSLQTKK-WQEKVISMNG-ITVNLSIKF 118

Breakpoint Cluster Region-related pleckstrin homology (PH) domain; The BCR gene is one of the two genes in the BCR-ABL complex, which is associated with the Philadelphia chromosome, a product of a reciprocal translocation between chromosomes 22 and 9. BCR is a GTPase-activating protein (GAP) for RAC1 (primarily) and CDC42. The Dbl region of BCR has the most RhoGEF activity for Cdc42, and less activity towards Rac and Rho. Since BCR possesses both GAP and GEF activities, it may function to temporally regulate the activity of these GTPases. It also displays serine/threonine kinase activity. The BCR protein contains multiple domains including an N-terminal kinase domain, a RhoGEF domain, a PH domain, a C1 domain, a C2 domain, and a C-terminal RhoGAP domain. This hierarchy is composed of arthropod BCRs. 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 281359606 542 MFLNQFNVVNQRLPIESNRNLRRMVRNSFIVELVDGHRKLRHLFLFNDVIACAKYKALGRDRIDYELKWFIPLKDVSIYE 621
Cdd:cd13368    1 FLNEFNNIQTKSMFPHQDRALRRLVKNSFIVELADGHRKLRHLFLFNDVIACAKYKSSGRTRITFELKWFIPLNDVTILE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281359606 622 EADPAVelKESSPANISQVKRNLRSVRDQLAMEVANSGSGAfrsgDKYRRKLADLESQLVLATPNLVLRLGNKaNNKTIT 701
Cdd:cd13368   81 EEAPAP--KESSPPNIEQLKSNACQVRDQLADRSRASTSGS----DKIRKKLADLEAQLVLASPNLVFRIGNK-NNKTYT 153

                        170       180
                 ....*....|....*....|....*..
gi 281359606 702 FFLSSDFERTQWIDSILSLKQKCNLPG 728
Cdd:cd13368  154 FFLSSEFERTQWIEAILTLQQTCPLPG 180

RhoGEF domain; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that pfam00169 domains invariably occur C-terminal to RhoGEF/DH domains.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281359606  366 ILSSIIQSETIYVECLNKMMQ-YKKAIHATLTTSQPVIreeeeNTIFFKIDELYDLHTGFLsdLKTIVSHEGGDVLIGEP 444
Cdd:pfam00621   1 VIKELLQTERSYVRDLEILVEvFLPPNSKPLSESEEEI-----KTIFSNIEEIYELHRQLL--LEELLKEWISIQRIGDI 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281359606  445 FRRLAEMFDLYSAFLHNYKNAIETVKKCSANNPQFKKIVSTIVLNLQTeQSLTLEDLLHKPVARVQINALVFNDLLRETP 524
Cdd:pfam00621  74 FLKFAPGFKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPEC-RGLDLNSFLIKPVQRIPRYPLLLKELLKHTP 152

                         170       180
                  ....*....|....*....|....
gi 281359606  525 NAHPDHQPLRQAQKIIQMFLNQFN 548
Cdd:pfam00621 153 PDHPDYEDLKKALEAIKEVAKQIN 176

C2 domain in the Active BCR (Breakpoint cluster region) Related protein; The ABR protein is similar to the breakpoint cluster region protein. It has homology to guanine nucleotide exchange proteins and GTPase-activating proteins (GAPs). ABR is expressed primarily in the brain, but also includes non-neuronal tissues such as the heart. It has been associated with human diseases such as Miller-Dieker syndrome in which mental retardation and malformations of the heart are present. ABR contains a RhoGEF domain and a PH-like domain upstream of its C2 domain and a RhoGAP domain downstream of this domain. A few members also contain a Bcr-Abl oncoprotein oligomerization domain at the very N-terminal end. Splice variants of ABR have been identified. ABR is found in a wide variety of organisms including chimpanzee, dog, mouse, rat, fruit fly, and mosquito. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281359606 770 LYMGVHGLEGLEQANDLYICVEVDSYGHYFRKATTkKICRSQT-PLWNESFMLELEGSQNVRILLYE-----------AK 837
Cdd:cd08686    1 LNVIVHSAQGFKQSANLYCTLEVDSFGYFVKKAKT-RVCRDTTePNWNEEFEIELEGSQTLRILCYEkcyskvkldgeGT 79

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 281359606 838 ERPLLKAKHILKLSLSWLTEtTQPKSIKLTEtLELGCSFRF 878
Cdd:cd08686   80 DAIMGKGQIQLDPQSLQTKK-WQEKVISMNG-ITVNLSIKF 118

Breakpoint Cluster Region-related pleckstrin homology (PH) domain; The BCR gene is one of the two genes in the BCR-ABL complex, which is associated with the Philadelphia chromosome, a product of a reciprocal translocation between chromosomes 22 and 9. BCR is a GTPase-activating protein (GAP) for RAC1 (primarily) and CDC42. The Dbl region of BCR has the most RhoGEF activity for Cdc42, and less activity towards Rac and Rho. Since BCR possesses both GAP and GEF activities, it may function to temporally regulate the activity of these GTPases. It also displays serine/threonine kinase activity. The BCR protein contains multiple domains including an N-terminal kinase domain, a RhoGEF domain, a PH domain, a C1 domain, a C2 domain, and a C-terminal RhoGAP domain. This hierarchy is composed of arthropod BCRs. 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 281359606 542 MFLNQFNVVNQRLPIESNRNLRRMVRNSFIVELVDGHRKLRHLFLFNDVIACAKYKALGRDRIDYELKWFIPLKDVSIYE 621
Cdd:cd13368    1 FLNEFNNIQTKSMFPHQDRALRRLVKNSFIVELADGHRKLRHLFLFNDVIACAKYKSSGRTRITFELKWFIPLNDVTILE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281359606 622 EADPAVelKESSPANISQVKRNLRSVRDQLAMEVANSGSGAfrsgDKYRRKLADLESQLVLATPNLVLRLGNKaNNKTIT 701
Cdd:cd13368   81 EEAPAP--KESSPPNIEQLKSNACQVRDQLADRSRASTSGS----DKIRKKLADLEAQLVLASPNLVFRIGNK-NNKTYT 153

                        170       180
                 ....*....|....*....|....*..
gi 281359606 702 FFLSSDFERTQWIDSILSLKQKCNLPG 728
Cdd:cd13368  154 FFLSSEFERTQWIEAILTLQQTCPLPG 180

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains. Improved coverage.

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281359606   366 ILSSIIQSETIYVECLNKMMQ-YKKAIHATLTtsqpVIREEEENTIFFKIDELYDLHTGFLSDLKTIVSHEGGDV-LIGE 443
Cdd:smart00325   1 VLKELLQTERNYVRDLKLLVEvFLKPLKKELK----LLSPNELETLFGNIEEIYEFHRDFLDELEERIEEWDDSVeRIGD 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281359606   444 PFRRLAEMFDLYSAFLHNYKNAIETVKKCsANNPQFKKIVSTIVLNLQTeQSLTLEDLLHKPVARVQINALVFNDLLRET 523
Cdd:smart00325  77 VFLKLEEFFKIYSEYCSNHPDALELLKKL-KKNPRFQKFLKEIESSPQC-RRLTLESLLLKPVQRLTKYPLLLKELLKHT 154

                          170       180
                   ....*....|....*....|....*
gi 281359606   524 PNAHPDHQPLRQAQKIIQMFLNQFN 548
Cdd:smart00325 155 PEDHEDREDLKKALKAIKELANQVN 179

Breakpoint Cluster Region-related pleckstrin homology (PH) domain; The BCR gene is one of the two genes in the BCR-ABL complex, which is associated with the Philadelphia chromosome, a product of a reciprocal translocation between chromosomes 22 and 9. BCR is a GTPase-activating protein (GAP) for RAC1 (primarily) and CDC42. The Dbl region of BCR has the most RhoGEF activity for Cdc42, and less activity towards Rac and Rho. Since BCR possesses both GAP and GEF activities, it may function to temporally regulate the activity of these GTPases. It also displays serine/threonine kinase activity. The BCR protein contains multiple domains including an N-terminal kinase domain, a RhoGEF domain, a PH domain, a C1 domain, a C2 domain, and a C-terminal RhoGAP domain. This hierarchy is composed of vertebrate BCRs. 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 281359606 563 RRMVRNSFIVELVDGHRKLRHLFLFNDVIACAKYKA-LGRDRIDYELKWFIPLKDVS--IYEEADPAVELKESSPANISQ 639
Cdd:cd13367   24 RQLLKDSFMVELVEGARKLRHVFLFTDLLLCAKLKKqIGGKSQQYDCKWYIPLADLSfqTVDESEAVPNIPLIPDEEIDA 103

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281359606 640 VKRNLRSVRDQLAMEV-ANSGSGAFrsgDKYRRKLADLESQLVLATPNLVLRLGNKaNNKTITFFLSSDFERTQWIDSIL 718
Cdd:cd13367  104 LKVKISQIKSDIQREKrANKGGKVL---ERLRKKLSEQESLLLLMSPSMAFRVHNR-NGKSYTFLISSDYERAEWRENIR 179

                 ....*.
gi 281359606 719 SLKQKC 724
Cdd:cd13367  180 EQQKKC 185

Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases; Also called Dbl-homologous (DH) domain. It appears that PH domains invariably occur C-terminal to RhoGEF/DH domains.

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281359606 366 ILSSIIQSETIYVECLNKMMQ-YKKAihatLTTSQPVIREEEENTIFFKIDELYDLHTGFLSDLKTIVSHEGGDV-LIGE 443
Cdd:cd00160    4 VIKELLQTERNYVRDLKLLVEvFLKP----LDKELLPLSPEEVELLFGNIEEIYEFHRIFLKSLEERVEEWDKSGpRIGD 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 281359606 444 PFRRLAEMFDLYSAFLHNYKNAIETVKKCSANNPQFKKIVSTIVLNLqteQSLTLEDLLHKPVARVQINALVFNDLLRET 523
Cdd:cd00160   80 VFLKLAPFFKIYSEYCSNHPDALELLKKLKKFNKFFQEFLEKAESEC---GRLKLESLLLKPVQRLTKYPLLLKELLKHT 156

                        170       180
                 ....*....|....*....|....*
gi 281359606 524 PNAHPDHQPLRQAQKIIQMFLNQFN 548
Cdd:cd00160  157 PDGHEDREDLKKALEAIKEVASQVN 181

unc89 pleckstrin homology (PH) domain; unc89 is a myofibrillar protein. unc89-B the largest isoform is composed of 53 immunoglobulin (Ig) domains, 2 Fn3 domains, a triplet of SH3, DH and PH domains at its N-terminus, and 2 protein kinase domains (PK1 and PK2) at its C-terminus. unc-89 mutants display disorganization of muscle A-bands, and usually lack M-lines. The COOH-terminal region of obscurin, the human homolog of unc89, interacts via two specific Ig-like domains with the NH(2)-terminal Z-disk region of titin, a protein that connects the Z line to the M line in the sarcomere and contributes to the contraction of striated muscle. obscurin is also thought to be involved in Ca2+/calmodulin via its IQ domains, as well as G protein-coupled signal transduction in the sarcomere via its RhoGEF/DH domain. The DH-PH region of OBSCN and unc89, the C. elegans homolog, has exchange activity for RhoA and Rho-1 respectively, but not for the small GTPases homologous to Cdc42 or Rac. 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 281359606 562 LRRMVRNS-FIVELVDGHRKLRHLFLFNDVIACAKYKALGRDRIDYELKWFIPLKDVSIYEEADP--AVELKESSPANIS 638
Cdd:cd13325    6 LGRLLRHDwFTVTDGEGKAKERYLFLFKSRILITKVRRISEDRSVFILKDIIRLPEVNVKQHPDDerTFELQPKLPAFGI 85

                         90
                 ....*....|.
gi 281359606 639 QVKrNLRSVRD 649
Cdd:cd13325   86 LPI-DFKAHKD 95

RA and RhoGAP domain-containing protein Pleckstrin homology PH domain; RARhoGAP (also called Rho GTPase-activating protein 20 and ARHGAP20 ) is thought to function in rearrangements of the cytoskeleton and cell signaling events that occur during spermatogenesis. RARhoGAP was also shown to be activated by Rap1 and to induce inactivation of Rho, resulting in the neurite outgrowth. Recent findings show that ARHGAP20, even although it is located in the middle of the MDR on 11q22-23, is expressed at higher levels in chronic lymphocytic leukemia patients with 11q22-23 and/or 13q14 deletions and its expression pattern suggests a functional link between cases with 11q22-23 and 13q14 deletions. The mechanism needs to be further studied. RARhoGAP contains a PH domain, a Ras-associating domain, a Rho-GAP domain, and ANXL repeats. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 281359606 572 VELVDGH-RKLRHLFLFNDVIACAKYKALGRdridYELKWFIPLKDVSIYEEADPaVELKESSP 634
Cdd:cd13319    9 VQLTRGLqTQERHLFLFSDVLVVAKPKSKNS----FKLKHKIRLSELWLASCVDE-VCEGSKSA 67