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Showing Protein Serine/threonine-protein kinase PAK 1 (HMDBP08499)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 4 metabolites
Identification
HMDB Protein ID HMDBP08499
Secondary Accession Numbers
  • 14211
Name Serine/threonine-protein kinase PAK 1
Synonyms
  1. Alpha-PAK
  2. PAK-1
  3. p21-activated kinase 1
  4. p65-PAK
Gene Name PAK1
Protein Type Unknown
Biological Properties
General Function Involved in protein kinase activity
Specific Function The activated kinase acts on a variety of targets. Likely to be the GTPase effector that links the Rho-related GTPases to the JNK MAP kinase pathway. Activated by CDC42 and RAC1. Involved in dissolution of stress fibers and reorganization of focal complexes. Involved in regulation of microtubule biogenesis through phosphorylation of TBCB. Activity is inhibited in cells undergoing apoptosis, potentially due to binding of CDC2L1 and CDC2L2
Pathways
  • Intracellular Signalling Through Adenosine Receptor A2a and Adenosine
  • Intracellular Signalling Through Adenosine Receptor A2b and Adenosine
Reactions Not Available
GO Classification
Function
binding
catalytic activity
transferase activity
transferase activity, transferring phosphorus-containing groups
kinase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
protein kinase activity
protein serine/threonine kinase activity
Process
phosphorus metabolic process
phosphate metabolic process
metabolic process
cellular metabolic process
protein amino acid phosphorylation
phosphorylation
Cellular Location
  1. Cytoplasm
  2. Cell junction
  3. focal adhesion
Gene Properties
Chromosome Location Chromosome:1
Locus 11q13-q14
SNPs PAK1
Gene Sequence 
>1638 bp
ATGTCAAATAACGGCCTAGACATTCAAGACAAACCCCCAGCCCCTCCGATGAGAAATACC
AGCACTATGATTGGAGCCGGCAGCAAAGATGCTGGAACCCTAAACCATGGTTCTAAACCT
CTGCCTCCAAACCCAGAGGAGAAGAAAAAGAAGGACCGATTTTACCGATCCATTTTACCT
GGAGATAAAACAAATAAAAAGAAAGAGAAAGAGCGGCCAGAGATTTCTCTCCCTTCAGAT
TTTGAACACACAATTCATGTCGGTTTTGATGCTGTCACAGGGGAGTTTACGGGAATGCCA
GAGCAGTGGGCCCGCTTGCTTCAGACATCAAATATCACTAAGTCGGAGCAGAAGAAAAAC
CCGCAGGCTGTTCTGGATGTGTTGGAGTTTTACAACTCGAAGAAGACATCCAACAGCCAG
AAATACATGAGCTTTACAGATAAGTCAGCTGAGGATTACAATTCTTCTAATGCCTTGAAT
GTGAAGGCTGTGTCTGAGACTCCTGCAGTGCCACCAGTTTCAGAAGATGAGGATGATGAT
GATGATGATGCTACCCCACCACCAGTGATTGCTCCACGCCCAGAGCACACAAAATCTGTA
TACACACGGTCTGTGATTGAACCACTTCCTGTCACTCCAACTCGGGACGTGGCTACATCT
CCCATTTCACCTACTGAAAATAACACCACTCCACCAGATGCTTTGACCCGGAATACTGAG
AAGCAGAAGAAGAAGCCTAAAATGTCTGATGAGGAGATCTTGGAGAAATTACGAAGCATA
GTGAGTGTGGGCGATCCTAAGAAGAAATATACACGGTTTGAGAAGATTGGACAAGGTGCT
TCAGGCACCGTGTACACAGCAATGGATGTGGCCACAGGACAGGAGGTGGCCATTAAGCAG
ATGAATCTTCAGCAGCAGCCCAAGAAAGAGCTGATTATTAATGAGATCCTGGTCATGAGG
GAAAACAAGAACCCAAACATTGTGAATTACTTGGACAGTTACCTCGTGGGAGATGAGCTG
TGGGTTGTTATGGAATACTTGGCTGGAGGCTCCTTGACAGATGTGGTGACAGAAACTTGC
ATGGATGAAGGCCAAATTGCAGCTGTGTGCCGTGAGTGTCTGCAGGCTCTGGAGTTCTTG
CATTCGAACCAGGTCATTCACAGAGACATCAAGAGTGACAATATTCTGTTGGGAATGGAT
GGCTCTGTCAAGCTAACTGACTTTGGATTCTGTGCACAGATAACCCCAGAGCAGAGCAAA
CGGAGCACCATGGTAGGAACCCCATACTGGATGGCACCAGAGGTTGTGACACGAAAGGCC
TATGGGCCCAAGGTTGACATCTGGTCCCTGGGCATCATGGCCATCGAAATGATTGAAGGG
GAGCCTCCATACCTCAATGAAAACCCTCTGAGAGCCTTGTACCTCATTGCCACCAATGGG
ACCCCAGAACTTCAGAACCCAGAGAAGCTGTCAGCTATCTTCCGGGACTTTCTGAACCGC
TGTCTCGAGATGGATGTGGAGAAGAGAGGTTCAGCTAAAGAGCTGCTACAGCATCAATTC
CTGAAGATTGCCAAGCCCCTCTCCAGCCTCACTCCACTGATTGCTGCAGCTAAGGAGGCA
ACAAAGAACAATCACTAA
Protein Properties
Number of Residues 545
Molecular Weight 60646.4
Theoretical pI 5.47
Pfam Domain Function
Signals
  • None
Transmembrane Regions
  • None
Protein Sequence 
>Serine/threonine-protein kinase PAK 1
MSNNGLDIQDKPPAPPMRNTSTMIGAGSKDAGTLNHGSKPLPPNPEEKKKKDRFYRSILP
GDKTNKKKEKERPEISLPSDFEHTIHVGFDAVTGEFTGMPEQWARLLQTSNITKSEQKKN
PQAVLDVLEFYNSKKTSNSQKYMSFTDKSAEDYNSSNALNVKAVSETPAVPPVSEDEDDD
DDDATPPPVIAPRPEHTKSVYTRSVIEPLPVTPTRDVATSPISPTENNTTPPDALTRNTE
KQKKKPKMSDEEILEKLRSIVSVGDPKKKYTRFEKIGQGASGTVYTAMDVATGQEVAIKQ
MNLQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAGGSLTDVVTETC
MDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQSK
RSTMVGTPYWMAPEVVTRKAYGPKVDIWSLGIMAIEMIEGEPPYLNENPLRALYLIATNG
TPELQNPEKLSAIFRDFLNRCLEMDVEKRGSAKELLQHQFLKIAKPLSSLTPLIAAAKEA
TKNNH
GenBank ID Protein 42794769
UniProtKB/Swiss-Prot ID Q13153
UniProtKB/Swiss-Prot Entry Name PAK1_HUMAN
PDB IDs
GenBank Gene ID NM_002576.4
GeneCard ID PAK1
GenAtlas ID PAK1
HGNC ID HGNC:8590
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M: Lysine acetylation targets protein complexes and co-regulates major cellular functions. Science. 2009 Aug 14;325(5942):834-40. doi: 10.1126/science.1175371. Epub 2009 Jul 16. [PubMed:19608861 ]
  3. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648 ]
  4. Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK: Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions. Sci Signal. 2009 Aug 18;2(84):ra46. doi: 10.1126/scisignal.2000007. [PubMed:19690332 ]
  5. Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S: Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. Anal Chem. 2009 Jun 1;81(11):4493-501. doi: 10.1021/ac9004309. [PubMed:19413330 ]
  6. Beausoleil SA, Villen J, Gerber SA, Rush J, Gygi SP: A probability-based approach for high-throughput protein phosphorylation analysis and site localization. Nat Biotechnol. 2006 Oct;24(10):1285-92. Epub 2006 Sep 10. [PubMed:16964243 ]
  7. Heibeck TH, Ding SJ, Opresko LK, Zhao R, Schepmoes AA, Yang F, Tolmachev AV, Monroe ME, Camp DG 2nd, Smith RD, Wiley HS, Qian WJ: An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells. J Proteome Res. 2009 Aug;8(8):3852-61. doi: 10.1021/pr900044c. [PubMed:19534553 ]
  8. Nola S, Sebbagh M, Marchetto S, Osmani N, Nourry C, Audebert S, Navarro C, Rachel R, Montcouquiol M, Sans N, Etienne-Manneville S, Borg JP, Santoni MJ: Scrib regulates PAK activity during the cell migration process. Hum Mol Genet. 2008 Nov 15;17(22):3552-65. doi: 10.1093/hmg/ddn248. Epub 2008 Aug 20. [PubMed:18716323 ]
  9. Chen S, Yin X, Zhu X, Yan J, Ji S, Chen C, Cai M, Zhang S, Zong H, Hu Y, Yuan Z, Shen Z, Gu J: The C-terminal kinase domain of the p34cdc2-related PITSLRE protein kinase (p110C) associates with p21-activated kinase 1 and inhibits its activity during anoikis. J Biol Chem. 2003 May 30;278(22):20029-36. Epub 2003 Mar 6. [PubMed:12624090 ]
  10. Li W, Guan KL: The Down syndrome cell adhesion molecule (DSCAM) interacts with and activates Pak. J Biol Chem. 2004 Jul 30;279(31):32824-31. Epub 2004 May 28. [PubMed:15169762 ]
  11. Brown JL, Stowers L, Baer M, Trejo J, Coughlin S, Chant J: Human Ste20 homologue hPAK1 links GTPases to the JNK MAP kinase pathway. Curr Biol. 1996 May 1;6(5):598-605. [PubMed:8805275 ]
  12. Sells MA, Knaus UG, Bagrodia S, Ambrose DM, Bokoch GM, Chernoff J: Human p21-activated kinase (Pak1) regulates actin organization in mammalian cells. Curr Biol. 1997 Mar 1;7(3):202-10. [PubMed:9395435 ]
  13. Manser E, Huang HY, Loo TH, Chen XQ, Dong JM, Leung T, Lim L: Expression of constitutively active alpha-PAK reveals effects of the kinase on actin and focal complexes. Mol Cell Biol. 1997 Mar;17(3):1129-43. [PubMed:9032240 ]
  14. Frost JA, Khokhlatchev A, Stippec S, White MA, Cobb MH: Differential effects of PAK1-activating mutations reveal activity-dependent and -independent effects on cytoskeletal regulation. J Biol Chem. 1998 Oct 23;273(43):28191-8. [PubMed:9774440 ]
  15. Zhao ZS, Manser E, Chen XQ, Chong C, Leung T, Lim L: A conserved negative regulatory region in alphaPAK: inhibition of PAK kinases reveals their morphological roles downstream of Cdc42 and Rac1. Mol Cell Biol. 1998 Apr;18(4):2153-63. [PubMed:9528787 ]
  16. Zenke FT, King CC, Bohl BP, Bokoch GM: Identification of a central phosphorylation site in p21-activated kinase regulating autoinhibition and kinase activity. J Biol Chem. 1999 Nov 12;274(46):32565-73. [PubMed:10551809 ]
  17. Parrini MC, Lei M, Harrison SC, Mayer BJ: Pak1 kinase homodimers are autoinhibited in trans and dissociated upon activation by Cdc42 and Rac1. Mol Cell. 2002 Jan;9(1):73-83. [PubMed:11804587 ]
  18. Vadlamudi RK, Barnes CJ, Rayala S, Li F, Balasenthil S, Marcus S, Goodson HV, Sahin AA, Kumar R: p21-activated kinase 1 regulates microtubule dynamics by phosphorylating tubulin cofactor B. Mol Cell Biol. 2005 May;25(9):3726-36. [PubMed:15831477 ]
  19. Talukder AH, Meng Q, Kumar R: CRIPak, a novel endogenous Pak1 inhibitor. Oncogene. 2006 Mar 2;25(9):1311-9. [PubMed:16278681 ]
  20. Lei M, Lu W, Meng W, Parrini MC, Eck MJ, Mayer BJ, Harrison SC: Structure of PAK1 in an autoinhibited conformation reveals a multistage activation switch. Cell. 2000 Aug 4;102(3):387-97. [PubMed:10975528 ]
  21. Mott HR, Nietlispach D, Evetts KA, Owen D: Structural analysis of the SH3 domain of beta-PIX and its interaction with alpha-p21 activated kinase (PAK). Biochemistry. 2005 Aug 23;44(33):10977-83. [PubMed:16101281 ]
  22. Lei M, Robinson MA, Harrison SC: The active conformation of the PAK1 kinase domain. Structure. 2005 May;13(5):769-78. [PubMed:15893667 ]