Conserved Protein Domain Family
PH_PDK1

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cd01262: PH_PDK1 
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3-Phosphoinositide dependent protein kinase 1 (PDK1) pleckstrin homology (PH) domain
PDK1 plays an important role in insulin and growth factor signalling cascades. It phosphorylates and activates many AGC (cAMP-dependent, cGMP-dependent, protein kinase C (PKC)) family of protein kinases members, including protein kinase B (PKB, also known as Akt), p70 ribosomal S6-kinase (S6K), serum and glucocorticoid responsive kinase (SGK), p90 ribosomal S6 kinase (RSK), and PKC. PDK1 contains an N-terminal serine/threonine kinase domain followed by a PH domain. Following binding of the PH domain to PtdIns(3,4,5)P3 and PtdIns(3,4)P2, PDK1 activates these enzymes by phosphorylating a Ser/Thr residue in their activation loop. 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: 241293
View PSSM: cd01262
Aligned: 30 rows
Threshold Bit Score: 136.576
Threshold Setting Gi: 313244013
Created: 4-Feb-2003
Updated: 2-Mar-2014
Structure
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Program:
Drawing:
Aligned Rows:
 
phosphoinosit..
Conserved site includes 7 residues -Click on image for an interactive view with Cn3D
Feature 1:phosphoinositide binding site [chemical binding site]
Evidence:
  • Structure:1W1D; Human PDK1 PH domain binds Inositol (1,3,4,5)-tetrakisphosphate, contacts at 4A
    View structure with Cn3D
  • Comment:PDK1 PH domain binds PtdIns(3,4,5)P3
  • Structure:1WIG; Human Human PDK1 PH domain binds Dic4-Phosphatidylinositol (3,4,5)- trisphosphate, contacts at 4A
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
Feature 1                                # #    # #                #        #                    
1W1D_A        36 KQAGGNPWHQFVENNLILKMGPVDKRKGLFARRRQLLLTE-----GPHLYYVDPvNKVLKGEIPWSq---ELRPEAKNFK 107
gi 5001830   238 DSFDSRWQDFLEPGESVVLISKLKKINKLTNKKVQLILTD-----KPQLICVDPgKMVTKGNIMWSddpsELNVQVSNSS 312
gi 66809601  801 IDQYQWSRFLLPNDEIILACGITEKRSGLITKKRQLIITD-----TPRIFYVDPvKMTQKGEITVDg---SLSAQQKSSK 872
gi 326437466 406 QAKESPWHSFLNEGELIIKTGLVDKRRGLFSKRRQLILTD-----TPRLIYIDPeALEIKGEIPWSn---ELQPQFKNMR 477
gi 320170589 479 QAQESQWHRFVQVDELIIKTGIIHKRKGLFSKRRQLVLTD-----KPRCLYIDVdKMEIKGEIPWSt---EMRFEVKNKK 550
gi 301123679 379 RRTSSLWNRFLLDDELIKMGGLISKRKGLFSKKRQLILTS-----KPRLIYIDPiRMKQKGEIPWSd---NLYVNSKSAT 450
gi 302767784 384 ENVHEPWQKFLFEGETILASSRVRKFRKLSVKKRQLILTD-----RPRLFYVHPiKLVFKGEVPWS----RDIYVRVEND 454
gi 281203995 398 QKDIVWNRFLLPNNEIILAIATLEKKTGLITKKRVMIITD-----TPRIFYVDPhKMIVKGEIPVD----STLSAESKSM 468
gi 313244013 378 KNKSNRWATFVDDDELIIKLGYMYKKRGLFSRKRMFLLTGgkiekLPRLIYVDAnSWEKKGEINLHg---KIKVHQKSFS 454
gi 328875244 483 QSTLVWNKLLLPNDEIILGMTPIVKKTGLISKQRHLIITD-----SPRIFWVDSsKMIIKGEIHVDl---TLLASIKSNK 554
                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*..
Feature 1                     #                                 
1W1D_A       108 TFFVHTP-----NRTYYLMDP-------SGNAHKWCRKIQEVWRQRY 142
gi 5001830   313 HFRICTP-----KKVSSFEDA-------KQRAWQWKKAIEDLQRCQK 347
gi 66809601  873 HFIINSK-----GRSRHFYDL-------DGQSKLWVDLINELNMLSF 907
gi 326437466 478 TFFVHTP-----NRTYYLEDV-------ERKSIAWVDTINHMLKLQK 512
gi 320170589 551 TFFIHTP-----NRTYYLEDL-------SADAYGWCEQFNALLKQYR 585
gi 301123679 451 AFDVVTP-----NRVYHLNDL-------VNGSKKWIEAINAALVRGM 485
gi 302767784 455 LKFCICT-----PKRTYNLED-------TKGQARVWKESIEKLVNAK 489
gi 281203995 469 RHFRGRH-----KHFFDLYNN-------CKRWVDYINDLKMLGVVNK 503
gi 313244013 455 RFYIIDPskgrdGRIYDLTDNnsnsdvpDAGAAQWIRKIQLVKEIYF 501
gi 328875244 555 HFTITSR-----GRTRHFNDTv------TQDSKRWVDLINNLKLLGS 590

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