Pleckstrin homology domain-containing family G member 7 pleckstrin homology (PH) domain; PLEKHG7 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG7 is proposed to functions as a guanine nucleotide exchange factor (GEF) and is involved in the regulation of Rho protein signal transduction. 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 193203662 434 KLIHEGPLELVENGRTVDMYAFLFNDMFVLTKTKKCASKLKVKGVP-----------IGKSEHYIVQRQPVPLDSCVFCD 502
Cdd:cd13245    1 QLLHEGPLTLIESGKTLDVYLFLFDDMLLITKMKKNLKKKKSSDSEnsmpsleltplIKEGGSYTVYKQPIPLDRLCLHD 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 193203662 503 ADSNdQATPMSLKFAFVIIHLTRYYQVVGIYTLQAADKADKELWIEKFQ 551
Cdd:cd13245   81 VDPN-EATANGLKHAFVLVHLNRYQQVIGVYTLQASSENTKQTWMSKLR 128

Pleckstrin homology domain-containing family G member 7 pleckstrin homology (PH) domain; PLEKHG7 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG7 is proposed to functions as a guanine nucleotide exchange factor (GEF) and is involved in the regulation of Rho protein signal transduction. 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 193203662 434 KLIHEGPLELVENGRTVDMYAFLFNDMFVLTKTKKCASKLKVKGVP-----------IGKSEHYIVQRQPVPLDSCVFCD 502
Cdd:cd13245    1 QLLHEGPLTLIESGKTLDVYLFLFDDMLLITKMKKNLKKKKSSDSEnsmpsleltplIKEGGSYTVYKQPIPLDRLCLHD 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 193203662 503 ADSNdQATPMSLKFAFVIIHLTRYYQVVGIYTLQAADKADKELWIEKFQ 551
Cdd:cd13245   81 VDPN-EATANGLKHAFVLVHLNRYQQVIGVYTLQASSENTKQTWMSKLR 128

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 193203662  190 AVWELFHTELVFLyRQLFVLRDVYKEPLKrcqveGCLLLVEPDL--LFGNLDQLCRISRTFcqsFLSLLStvdkENWDCT 267
Cdd:pfam00621   1 VIKELLQTERSYV-RDLEILVEVFLPPNS-----KPLSESEEEIktIFSNIEEIYELHRQL---LLEELL----KEWISI 67

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203662  268 QLVVDLFERFSKGpstISAYQAYCINYKATMEYLGSIRQKEERFTEFERICLADERCFRLQLEDLLIAPLQRITRLPILL 347
Cdd:pfam00621  68 QRIGDIFLKFAPG---FKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLL 144

                         170       180       190
                  ....*....|....*....|....*....|..
gi 193203662  348 REIHKRSEEE-ESKGKVEKVIDTMTESLRSID 378
Cdd:pfam00621 145 KELLKHTPPDhPDYEDLKKALEAIKEVAKQIN 176

Pleckstrin homology domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203662  433 RKLIHEGPLELVENGRtvDMYAFLFNDMFVLTK-TKKCASKLKVKGVPIGKSEHYIVQRQPVPLDSCVFcdADSNDQAtp 511
Cdd:pfam16652  22 RKLLHSGKLYKVKSNK--ELVGFLFNDFLLLTQpVKPLSSAGTDKLFSSKSNIQYKMYKTPIFLNEVMV--KLPTDPS-- 95

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 193203662  512 mSLKFAFVIIHLTRyyqvvgIYTLQAADKADKELWIEKFQESIENY 557
Cdd:pfam16652  96 -SSEPTFQLSHIDR------VYTLKAESPNERTAWVKKIKEASELY 134

RhoGEF, Guanine nucleotide exchange factor for Rho/Rac/Cdc42-like GTPases [Signal transduction mechanisms];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203662  180 IPSSKHKYLQAVWELFHTELVFLyRQLFVLRDVYKEPL---------KRCQVEGCLllvepdllFGNLDQLCRISRTFCQ 250
Cdd:COG5422   478 LPKQEIKRQEAIYEVIYTERDFV-KDLEYLRDTWIKPLeesniipenARRNFIKHV--------FANINEIYAVNSKLLK 548

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203662  251 SFLS--LLSTVDKENWDCTQLVVDLFERFskgpstisayqaycINYKATMEYLGSIRQKEE----RFTEFERICLADERC 324
Cdd:COG5422   549 ALTNrqCLSPIVNGIADIFLDYVPKFEPF--------------IKYGASQPYAKYEFEREKsvnpNFARFDHEVERLDES 614

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203662  325 FRLQLEDLLIAPLQRITRLPILLREIHKRSEEEES-KGKVEKVIDTMTESLRSIDDSVQWLHNFERLQQLQTQVVWPNis 403
Cdd:COG5422   615 RKLELDGYLTKPTTRLARYPLLLEEVLKFTDPDNPdTEDIPKVIDMLREFLSRLNFESGKAENRGDLFHLNQQLLFKP-- 692

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203662  404 dlepkSYVPDFLRvalsrqfcenllaHPRRKLIHEGPLELVENGRT-----VDMYAFLFNDMFVLTKTKKcasklkvkgv 478
Cdd:COG5422   693 -----EYVNLGLN-------------DEYRKIIFKGVLKRKAKSKTdgslrGDIQFFLLDNMLLFCKAKA---------- 744

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203662  479 pIGKSEHYIVQRQPVPLDSCVFC-DADSND------------------QATPMSLKFAFVIIHLTRYYQVvgiyTLQAAD 539
Cdd:COG5422   745 -VNKWRQHKVFQRPIPLELLFISpDEDSPDraeylkpapsadvldpayNTKPPKNAYGFELYGNGQRYQI----TLYAET 819

                         410
                  ....*....|
gi 193203662  540 KADKELWIEK 549
Cdd:COG5422   820 HAGRDTWLEH 829

Pleckstrin homology domain-containing family G member 7 pleckstrin homology (PH) domain; PLEKHG7 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG7 is proposed to functions as a guanine nucleotide exchange factor (GEF) and is involved in the regulation of Rho protein signal transduction. 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 193203662 434 KLIHEGPLELVENGRTVDMYAFLFNDMFVLTKTKKCASKLKVKGVP-----------IGKSEHYIVQRQPVPLDSCVFCD 502
Cdd:cd13245    1 QLLHEGPLTLIESGKTLDVYLFLFDDMLLITKMKKNLKKKKSSDSEnsmpsleltplIKEGGSYTVYKQPIPLDRLCLHD 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 193203662 503 ADSNdQATPMSLKFAFVIIHLTRYYQVVGIYTLQAADKADKELWIEKFQ 551
Cdd:cd13245   81 VDPN-EATANGLKHAFVLVHLNRYQQVIGVYTLQASSENTKQTWMSKLR 128

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 193203662  190 AVWELFHTELVFLyRQLFVLRDVYKEPLKrcqveGCLLLVEPDL--LFGNLDQLCRISRTFcqsFLSLLStvdkENWDCT 267
Cdd:pfam00621   1 VIKELLQTERSYV-RDLEILVEVFLPPNS-----KPLSESEEEIktIFSNIEEIYELHRQL---LLEELL----KEWISI 67

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203662  268 QLVVDLFERFSKGpstISAYQAYCINYKATMEYLGSIRQKEERFTEFERICLADERCFRLQLEDLLIAPLQRITRLPILL 347
Cdd:pfam00621  68 QRIGDIFLKFAPG---FKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLL 144

                         170       180       190
                  ....*....|....*....|....*....|..
gi 193203662  348 REIHKRSEEE-ESKGKVEKVIDTMTESLRSID 378
Cdd:pfam00621 145 KELLKHTPPDhPDYEDLKKALEAIKEVAKQIN 176

Pleckstrin homology domain-containing family G member 5 and 6 pleckstrin homology (PH) domain; PLEKHG5 has a RhoGEF DH/double-homology domain in tandem with a PH domain which is involved in phospholipid binding. PLEKHG5 activates the nuclear factor kappa B (NFKB1) signaling pathway. Mutations in PLEKHG5 are associated with autosomal recessive distal spinal muscular atrophy. PLEKHG6 (also called MyoGEF) has no known function to date. 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 193203662 433 RKLIHEGPLELVEN-GRTVDMYAFLFNDMFVLTKTKKcASKLKVKgvpigksehyiVQRQPVPLDSCVFCD-ADSNdqat 510
Cdd:cd13244    1 RRLLLEGDLRLKEGkGSKVDVHCFLFTDMLLICKPVK-RKKDRLK-----------VIRPPYLVDKLVVQElKDPG---- 64

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 193203662 511 pmslkfAFVIIHLTRYYQVVGIYTLQAADKADKELWIEKFQ 551
Cdd:cd13244   65 ------GFLLVYLNEFHTAVAAYTFQTSSQEDTRRWLDAIR 99

Pleckstrin homology domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203662  433 RKLIHEGPLELVENGRtvDMYAFLFNDMFVLTK-TKKCASKLKVKGVPIGKSEHYIVQRQPVPLDSCVFcdADSNDQAtp 511
Cdd:pfam16652  22 RKLLHSGKLYKVKSNK--ELVGFLFNDFLLLTQpVKPLSSAGTDKLFSSKSNIQYKMYKTPIFLNEVMV--KLPTDPS-- 95

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 193203662  512 mSLKFAFVIIHLTRyyqvvgIYTLQAADKADKELWIEKFQESIENY 557
Cdd:pfam16652  96 -SSEPTFQLSHIDR------VYTLKAESPNERTAWVKKIKEASELY 134

Rho guanine nucleotide exchange factor Pleckstrin homology domain; RhoGEFs belongs to regulator of G-protein signaling (RGS) domain-containing RhoGEFs that are RhoA-selective and directly activated by the Galpha12/13 family of heterotrimeric G proteins. The members here all contain Dbl homology (DH)-PH domains. In addition some members contain N-terminal C1 (Protein kinase C conserved region 1) domains, PDZ (also called DHR/Dlg homologous regions) domains, ANK (ankyrin) domains, and RGS (Regulator of G-protein signalling) domains or C-terminal ATP-synthase B subunit. The DH-PH domains bind and catalyze the exchange of GDP for GTP on RhoA. RhoGEF2/Rho guanine nucleotide exchange factor 2, p114RhoGEF/p114 Rho guanine nucleotide exchange factor, p115RhoGEF, p190RhoGEF, PRG/PDZ Rho guanine nucleotide exchange factor, RhoGEF 11, RhoGEF 12, RhoGEF 18, AKAP13/A-kinase anchoring protein 13, and LARG/Leukemia-associated Rho guanine nucleotide exchange factor are included in this CD. 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 193203662 435 LIHEGPLEL-VENGRTVDMYAFLFNDMFVLTkTKKcASKLKVKGVPIGKSEhYIVQRQPV-PLDSCVfcdadSNDQATPM 512
Cdd:cd13329    1 LIHEGPLTWkVARGKLIEVHVLLLEDLLVLL-QKQ-DDKYLLKLHLTGSFD-SKDTKSPViKLSTLL-----VREVATDK 72

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 193203662 513 slKFAFVIIHLTRYYQvvgIYTLQAADKADKELWIEKFQESI 554
Cdd:cd13329   73 --KAFFLISTSKNGPQ---MYELVANSSSERKTWIKHISDAV 109

Rho guanine nucleotide exchange factor 3 Pleckstrin homology (PH) domain; RhoGEF3/XPLN, a Rho family GEF, preferentially stimulates guanine nucleotide exchange on RhoA and RhoB, but not RhoC, RhoG, Rac1, or Cdc42 in vitro. It also possesses transforming activity. RhoGEF3/XPLN contains a tandem Dbl homology and PH domain, but lacks homology with other known functional domains or motifs. It is expressed in the brain, skeletal muscle, heart, kidney, platelets, and macrophage and neuronal cell lines. 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 193203662 433 RKLIHEGPLElveNGRTVDMYAFLFNDMFVLTKtkkcasklkvkgvPIGKSE--HYIVQRQPVPLDSCVFCDADSNDQAT 510
Cdd:cd10572   18 RLLLCHGELK---NNRGTKLHVFLFEEVLVLTR-------------PVTRNEqlCYQVYRQPIPVADLVLEDLPDGEVRL 81

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|..
gi 193203662 511 PMSLKFAFVIIHLTRYYQVVGI--------YTLQAADKADKELWIEKFQESI 554
Cdd:cd10572   82 GGSFRGAFSNNERAKNFFRVSFtdrslgqsHTLQANDEFDKQQWLNCIRQAV 133

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 193203662  435 LIHEGPL---ELVENGRTVDMYAFLFNDMFVLTKTKKCASKLKVKGVpigksehyivqrqpVPLDSCVFCDADSNDQatp 511
Cdd:pfam00169   1 VVKEGWLlkkGGGKKKSWKKRYFVLFDGSLLYYKDDKSGKSKEPKGS--------------ISLSGCEVVEVVASDS--- 63

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 193203662  512 MSLKFAFVIIHLTRyyQVVGIYTLQAADKADKELWIEKFQESIE 555
Cdd:pfam00169  64 PKRKFCFELRTGER--TGKRTYLLQAESEEERKDWIKAIQSAIR 105

Ephexin Pleckstrin homology (PH) domain; Ephexin-1 (also called NGEF/ neuronal guanine nucleotide exchange factor) plays a role in the homeostatic modulation of presynaptic neurotransmitter release. Specific functions are still unknown for Ephexin-2 (also called RhoGEF19) and Ephexin-3 (also called Rho guanine nucleotide exchange factor 5/RhoGEF5, Transforming immortalized mammary oncogene/p60 TIM, and NGEF/neuronalGEF). Ephexin-4 (also called RhoGEF16) acts downstream of EphA2 to promote ligand-independent breast cancer cell migration and invasion toward epidermal growth factor through activation of RhoG. This in turn results in the activation of RhoG which recruits ELMO2 and Dock4 to form a complex with EphA2 at the tips of cortactin-rich protrusions in migrating breast cancer cells. Ephexin-5 is the specific GEF for RhoA activation and the regulation of vascular smooth muscle contractility. It interacts with EPHA4 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. The members of the Ephexin family contains a RhoGEF (DH) followed by a PH domain and an SH3 domain. The ephexin PH domain is believed to act with the DH domain in mediating protein-protein interactions. 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 193203662 428 LAHPRRKLIHEGPL-ELVENG---------RTVDMYAFLFNDMFVLTKTKkcasklkvkgvpigKSEHYIVqrqpvpLDS 497
Cdd:cd01221    7 LISSSRWLVKRGELtELVEDGgsltfrkkfSKTPVYLFLFNDLLLITKKK--------------SEERYLV------LDY 66

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 193203662 498 CVF-----CDADSNDQATPMSLKFAFvIIHLTRYYQVVGI-YTLQAADKADKELWIEKF 550
Cdd:cd01221   67 APRnlvqvEEVEDPLQLPQPLGKNLF-LLTLLENHEGKTVeLLLSAESESDRERWLSAL 124

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
                 ....*....|....*....|....*....|....*....|....
gi 193203662 433 RKLIHEGPLELVENGRTVDMYAFLFNDMFVLTKTkKCASKLKVK 476
Cdd:cd13319    1 RTFLLEGPVQLTRGLQTQERHLFLFSDVLVVAKP-KSKNSFKLK 43