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 351051169 425 KLIHEGPLELVENGRTVDMYAFLFNDMFVLTKTKKCASKLKVKGVP-----------IGKSEHYIVQRQPVPLDSCVFCD 493
Cdd:cd13245    1 QLLHEGPLTLIESGKTLDVYLFLFDDMLLITKMKKNLKKKKSSDSEnsmpsleltplIKEGGSYTVYKQPIPLDRLCLHD 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 351051169 494 ADSNdQATPMSLKFAFVIIHLTRYYQVVGIYTLQAADKADKELWIEKFQ 542
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 351051169 425 KLIHEGPLELVENGRTVDMYAFLFNDMFVLTKTKKCASKLKVKGVP-----------IGKSEHYIVQRQPVPLDSCVFCD 493
Cdd:cd13245    1 QLLHEGPLTLIESGKTLDVYLFLFDDMLLITKMKKNLKKKKSSDSEnsmpsleltplIKEGGSYTVYKQPIPLDRLCLHD 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 351051169 494 ADSNdQATPMSLKFAFVIIHLTRYYQVVGIYTLQAADKADKELWIEKFQ 542
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 351051169  181 AVWELFHTELVFLyRQLFVLRDVYKEPLKrcqveGCLLLVEPDL--LFGNLDQLCRISRTFcqsFLSLLStvdkENWDCT 258
Cdd:pfam00621   1 VIKELLQTERSYV-RDLEILVEVFLPPNS-----KPLSESEEEIktIFSNIEEIYELHRQL---LLEELL----KEWISI 67

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351051169  259 QLVVDLFERFSKGpstISAYQAYCINYKATMEYLGSIRQKEERFTEFERICLADERCFRLQLEDLLIAPLQRITRLPILL 338
Cdd:pfam00621  68 QRIGDIFLKFAPG---FKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLL 144

                         170       180       190
                  ....*....|....*....|....*....|..
gi 351051169  339 REIHKRSEEE-ESKGKVEKVIDTMTESLRSID 369
Cdd:pfam00621 145 KELLKHTPPDhPDYEDLKKALEAIKEVAKQIN 176

Pleckstrin homology domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351051169  424 RKLIHEGPLELVENGRtvDMYAFLFNDMFVLTK-TKKCASKLKVKGVPIGKSEHYIVQRQPVPLDSCVFcdADSNDQAtp 502
Cdd:pfam16652  22 RKLLHSGKLYKVKSNK--ELVGFLFNDFLLLTQpVKPLSSAGTDKLFSSKSNIQYKMYKTPIFLNEVMV--KLPTDPS-- 95

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 351051169  503 mSLKFAFVIIHLTRyyqvvgIYTLQAADKADKELWIEKFQESIENY 548
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 351051169  171 IPSSKHKYLQAVWELFHTELVFLyRQLFVLRDVYKEPL---------KRCQVEGCLllvepdllFGNLDQLCRISRTFCQ 241
Cdd:COG5422   478 LPKQEIKRQEAIYEVIYTERDFV-KDLEYLRDTWIKPLeesniipenARRNFIKHV--------FANINEIYAVNSKLLK 548

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351051169  242 SFLS--LLSTVDKENWDCTQLVVDLFERFskgpstisayqaycINYKATMEYLGSIRQKEE----RFTEFERICLADERC 315
Cdd:COG5422   549 ALTNrqCLSPIVNGIADIFLDYVPKFEPF--------------IKYGASQPYAKYEFEREKsvnpNFARFDHEVERLDES 614

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351051169  316 FRLQLEDLLIAPLQRITRLPILLREIHKRSEEEES-KGKVEKVIDTMTESLRSIDDSVQWLHNFERLQQLQTQVVWPNis 394
Cdd:COG5422   615 RKLELDGYLTKPTTRLARYPLLLEEVLKFTDPDNPdTEDIPKVIDMLREFLSRLNFESGKAENRGDLFHLNQQLLFKP-- 692

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351051169  395 dlepkSYVPDFLRvalsrqfcenllaHPRRKLIHEGPLELVENGRT-----VDMYAFLFNDMFVLTKTKKcasklkvkgv 469
Cdd:COG5422   693 -----EYVNLGLN-------------DEYRKIIFKGVLKRKAKSKTdgslrGDIQFFLLDNMLLFCKAKA---------- 744

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351051169  470 pIGKSEHYIVQRQPVPLDSCVFC-DADSND------------------QATPMSLKFAFVIIHLTRYYQVvgiyTLQAAD 530
Cdd:COG5422   745 -VNKWRQHKVFQRPIPLELLFISpDEDSPDraeylkpapsadvldpayNTKPPKNAYGFELYGNGQRYQI----TLYAET 819

                         410
                  ....*....|
gi 351051169  531 KADKELWIEK 540
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 351051169 425 KLIHEGPLELVENGRTVDMYAFLFNDMFVLTKTKKCASKLKVKGVP-----------IGKSEHYIVQRQPVPLDSCVFCD 493
Cdd:cd13245    1 QLLHEGPLTLIESGKTLDVYLFLFDDMLLITKMKKNLKKKKSSDSEnsmpsleltplIKEGGSYTVYKQPIPLDRLCLHD 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 351051169 494 ADSNdQATPMSLKFAFVIIHLTRYYQVVGIYTLQAADKADKELWIEKFQ 542
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 351051169  181 AVWELFHTELVFLyRQLFVLRDVYKEPLKrcqveGCLLLVEPDL--LFGNLDQLCRISRTFcqsFLSLLStvdkENWDCT 258
Cdd:pfam00621   1 VIKELLQTERSYV-RDLEILVEVFLPPNS-----KPLSESEEEIktIFSNIEEIYELHRQL---LLEELL----KEWISI 67

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351051169  259 QLVVDLFERFSKGpstISAYQAYCINYKATMEYLGSIRQKEERFTEFERICLADERCFRLQLEDLLIAPLQRITRLPILL 338
Cdd:pfam00621  68 QRIGDIFLKFAPG---FKVYSTYCSNYPKALKLLKKLLKKNPKFRAFLEELEANPECRGLDLNSFLIKPVQRIPRYPLLL 144

                         170       180       190
                  ....*....|....*....|....*....|..
gi 351051169  339 REIHKRSEEE-ESKGKVEKVIDTMTESLRSID 369
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 351051169 424 RKLIHEGPLELVEN-GRTVDMYAFLFNDMFVLTKTKKcASKLKVKgvpigksehyiVQRQPVPLDSCVFCD-ADSNdqat 501
Cdd:cd13244    1 RRLLLEGDLRLKEGkGSKVDVHCFLFTDMLLICKPVK-RKKDRLK-----------VIRPPYLVDKLVVQElKDPG---- 64

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 351051169 502 pmslkfAFVIIHLTRYYQVVGIYTLQAADKADKELWIEKFQ 542
Cdd:cd13244   65 ------GFLLVYLNEFHTAVAAYTFQTSSQEDTRRWLDAIR 99

Pleckstrin homology domain;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351051169  424 RKLIHEGPLELVENGRtvDMYAFLFNDMFVLTK-TKKCASKLKVKGVPIGKSEHYIVQRQPVPLDSCVFcdADSNDQAtp 502
Cdd:pfam16652  22 RKLLHSGKLYKVKSNK--ELVGFLFNDFLLLTQpVKPLSSAGTDKLFSSKSNIQYKMYKTPIFLNEVMV--KLPTDPS-- 95

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 351051169  503 mSLKFAFVIIHLTRyyqvvgIYTLQAADKADKELWIEKFQESIENY 548
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 351051169 426 LIHEGPLEL-VENGRTVDMYAFLFNDMFVLTkTKKcASKLKVKGVPIGKSEhYIVQRQPV-PLDSCVfcdadSNDQATPM 503
Cdd:cd13329    1 LIHEGPLTWkVARGKLIEVHVLLLEDLLVLL-QKQ-DDKYLLKLHLTGSFD-SKDTKSPViKLSTLL-----VREVATDK 72

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|..
gi 351051169 504 slKFAFVIIHLTRYYQvvgIYTLQAADKADKELWIEKFQESI 545
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 351051169 435 VENGRTVDMYAFLFNDMFVLTKtkkcasklkvkgvPIGKSE--HYIVQRQPVPLDSCVFCDADSNDQATPMSLKFAFVII 512
Cdd:cd10572   26 LKNNRGTKLHVFLFEEVLVLTR-------------PVTRNEqlCYQVYRQPIPVADLVLEDLPDGEVRLGGSFRGAFSNN 92

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 351051169 513 HLTRYYQVVGI--------YTLQAADKADKELWIEKFQESI 545
Cdd:cd10572   93 ERAKNFFRVSFtdrslgqsHTLQANDEFDKQQWLNCIRQAV 133

PH domain; PH stands for pleckstrin homology.

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 351051169  426 LIHEGPL---ELVENGRTVDMYAFLFNDMFVLTKTKKCASKLKVKGVpigksehyivqrqpVPLDSCVFCDADSNDQatp 502
Cdd:pfam00169   1 VVKEGWLlkkGGGKKKSWKKRYFVLFDGSLLYYKDDKSGKSKEPKGS--------------ISLSGCEVVEVVASDS--- 63

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 351051169  503 MSLKFAFVIIHLTRyyQVVGIYTLQAADKADKELWIEKFQESIE 546
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 351051169 419 LAHPRRKLIHEGPL-ELVENG---------RTVDMYAFLFNDMFVLTKTKkcasklkvkgvpigKSEHYIVqrqpvpLDS 488
Cdd:cd01221    7 LISSSRWLVKRGELtELVEDGgsltfrkkfSKTPVYLFLFNDLLLITKKK--------------SEERYLV------LDY 66

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 351051169 489 CVF-----CDADSNDQATPMSLKFAFvIIHLTRYYQVVGI-YTLQAADKADKELWIEKF 541
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 351051169 424 RKLIHEGPLELVENGRTVDMYAFLFNDMFVLTKTkKCASKLKVK 467
Cdd:cd13319    1 RTFLLEGPVQLTRGLQTQERHLFLFSDVLVVAKP-KSKNSFKLK 43