3FEH,3FM8


Conserved Protein Domain Family
PH2_ADAP

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cd01251: PH2_ADAP 
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ArfGAP with dual PH domains Pleckstrin homology (PH) domain, repeat 2
ADAP (also called centaurin alpha) is a phophatidlyinositide binding protein consisting of an N-terminal ArfGAP domain and two PH domains. In response to growth factor activation, PI3K phosphorylates phosphatidylinositol 4,5-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 1 is recruited to the plasma membrane following growth factor stimulation by specific binding of its PH domain to phosphatidylinositol 3,4,5-trisphosphate. Centaurin alpha 2 is constitutively bound to the plasma membrane since it binds phosphatidylinositol 4,5-bisphosphate and phosphatidylinositol 3,4,5-trisphosphate with equal affinity. This cd contains the second 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.
Statistics
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PSSM-Id: 241282
View PSSM: cd01251
Aligned: 27 rows
Threshold Bit Score: 153.129
Threshold Setting Gi: 148687216
Created: 4-Feb-2003
Updated: 2-Mar-2014
Structure
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Program:
Drawing:
Aligned Rows:
 
putative
Conserved site includes 7 residues -Click on image for an interactive view with Cn3D
Feature 1:putative phosphoinositide binding site [chemical binding site]
Evidence:
  • Comment:binds PIP3 head group (IP4)
  • Comment:PH2 contains the canonical KXn(K/R)XR motif which is important for high-affinity 3-phosphoinositide-binding, PH1 has a leucine in place of the (K/R) residue, which is not seen in any other known phosphoinositide-binding PH domains

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                 #       # # #            #         #                                   
3FEH_A       268 NYLKEGYMEKTGPKqTEGFRKRWFTMDD--RRLMYFKDPLDAFARGEVFIGSKESGYTVLHGFPPSTQgh----hWPHGI 341
gi 49901314  254 SFLKEGYMEKTGPRqTEGFKKRWFTLDH--RRLMYFKDPLDAFAKGEVFLGHRDHGYRVTIGLPAGSHcn---gaWQFGI 328
gi 50757819  253 NYIKEGYMEKTGPKqKETFKMRWFSLDSeeRNLLYFKNPLDAFPQGQVFIGRRVEGYEVRAGLPQGISvk----kRKSGI 328
gi 62896611  255 NYLKQGFMEKTGPKqKEPFKKRWFALDCheRRLLYYKNPLDAFEQGQVFLGNKEQGYEAYEDLPKGIRgn----rWKAGL 330
gi 92081464  246 KMIKEGWMSKTGPKaKEKFRQRWFSLVG--TLIWYYNEPLDPHPIGFIPLGSKTFGYGIMKGLPLRITv------EGCGI 317
gi 118344158 253 HQRKQGWMEKTGPKlTEPYRKRWFSLEN--RRLLYFEKPLDPYPRGEIYLGSRSEGYMVRDGLPAGQTe------HGFGI 324
gi 148687216 252 NYLKEGYMEKTGPKqTEGFRKRWFTMDD--RRLMYFKDPLDAFARGEVFIGIRDQGSGVSSFSPRADPagvlgvrYFSKR 329
gi 196000688 259 EFLHEGYLEKTGPKeNGAFRRRWFSLYD--RKLMYFKGPLEPYPLGEIDIGLQDRGYKVQEDDIASHQr-----gDGFCF 331
gi 292611763 254 NYLKEGYMEKTGPLqREPFKKRWFILDSmdRKLLYFKTQLDAIELGVVFIGSENHGYSVRECVPKGTRgn----kWKCGV 329
gi 345322227 169 SFLKEGYMEKRGPGpRDGFKRRWFTLDR--RRLMYFKDPLDAFAKGEVFIGSREHGYDIRRGLPLGVPqgh--gtWQHGL 244
                         90       100       110
                 ....*....|....*....|....*....|..
Feature 1              #                         
3FEH_A       342 TIVTPDRKFLFACETESDQREWVAAFQKAVDR 373
gi 49901314  329 TIETPERSFLFTCETDTEQKDWMSHFNTLICT 360
gi 50757819  329 TMVTPARDFLFLCENDKEQREWIDALNGVIAQ 360
gi 62896611  331 TIVTPERRFVLTCPSEKEQQEWLESLRGVLSS 362
gi 92081464  318 TVHTPDRVYALICSDIKSRDEWYTAIDQVLES 349
gi 118344158 325 TITTPYRDYLLCCEDKEEQKSWINEIKSITTQ 356
gi 148687216 330 TLCTGPESTCLGPPVSLGQLAGATGRKPSLQG 361
gi 196000688 332 VFKTPGRNYYLRADSASEKRKWMRALNEALDS 363
gi 292611763 330 IVETPDRQFVFMCEQERDQREWVEALKTVISK 361
gi 345322227 245 TLVTPDRHYLFACEMESEQNDWFSTFSRVIEK 276

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