Serine/threonine-protein kinase PAK 5

Details

Name
Serine/threonine-protein kinase PAK 5
Synonyms
  • 2.7.11.1
  • KIAA1264
  • p21-activated kinase 5
  • p21-activated kinase 7
  • PAK-5
  • PAK-7
  • PAK7
Gene Name
PAK5
Organism
Humans
Amino acid sequence
>lcl|BSEQ0051898|Serine/threonine-protein kinase PAK 5
MFGKKKKKIEISGPSNFEHRVHTGFDPQEQKFTGLPQQWHSLLADTANRPKPMVDPSCIT
PIQLAPMKTIVRGNKPCKETSINGLLEDFDNISVTRSNSLRKESPPTPDQGASSHGPGHA
EENGFITFSQYSSESDTTADYTTEKYREKSLYGDDLDPYYRGSHAAKQNGHVMKMKHGEA
YYSEVKPLKSDFARFSADYHSHLDSLSKPSEYSDLKWEYQRASSSSPLDYSFQFTPSRTA
GTSGCSKESLAYSESEWGPSLDDYDRRPKSSYLNQTSPQPTMRQRSRSGSGLQEPMMPFG
ASAFKTHPQGHSYNSYTYPRLSEPTMCIPKVDYDRAQMVLSPPLSGSDTYPRGPAKLPQS
QSKSGYSSSSHQYPSGYHKATLYHHPSLQSSSQYISTASYLSSLSLSSSTYPPPSWGSSS
DQQPSRVSHEQFRAALQLVVSPGDPREYLANFIKIGEGSTGIVCIATEKHTGKQVAVKKM
DLRKQQRRELLFNEVVIMRDYHHDNVVDMYSSYLVGDELWVVMEFLEGGALTDIVTHTRM
NEEQIATVCLSVLRALSYLHNQGVIHRDIKSDSILLTSDGRIKLSDFGFCAQVSKEVPKR
KSLVGTPYWMAPEVISRLPYGTEVDIWSLGIMVIEMIDGEPPYFNEPPLQAMRRIRDSLP
PRVKDLHKVSSVLRGFLDLMLVREPSQRATAQELLGHPFLKLAGPPSCIVPLMRQYRHH
Number of residues
719
Molecular Weight
80744.2
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / protein serine/threonine kinase activity / Rac GTPase binding
Processes
actin cytoskeleton organization / activation of protein kinase activity / apoptotic process / cell growth / cell migration / cell proliferation / cytoskeleton organization / learning / locomotory behavior / memory / negative regulation of extrinsic apoptotic signaling pathway / regulation of apoptotic process / regulation of MAPK cascade / regulation of mitotic cell cycle / Rho protein signal transduction / signal transduction / signal transduction by protein phosphorylation / stress-activated protein kinase signaling cascade
Components
cytoplasm / mitochondrion / nucleoplasm
General Function
Serine/threonine protein kinase that plays a role in a variety of different signaling pathways including cytoskeleton regulation, cell migration, proliferation or cell survival. Activation by various effectors including growth factor receptors or active CDC42 and RAC1 results in a conformational change and a subsequent autophosphorylation on several serine and/or threonine residues. Phosphorylates the proto-oncogene RAF1 and stimulates its kinase activity. Promotes cell survival by phosphorylating the BCL2 antagonist of cell death BAD. Phosphorylates CTNND1, probably to regulate cytoskeletal organization and cell morphology. Keeps microtubules stable through MARK2 inhibition and destabilizes the F-actin network leading to the disappearance of stress fibers and focal adhesions.
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Mitochondrion
Gene sequence
>lcl|BSEQ0051899|Serine/threonine-protein kinase PAK 5 (PAK5)
ATGTTTGGGAAGAAAAAGAAAAAGATTGAAATATCTGGCCCGTCCAACTTTGAACACAGG
GTTCATACTGGGTTTGATCCACAAGAGCAGAAGTTTACCGGCCTTCCCCAGCAGTGGCAC
AGCCTGTTAGCAGATACGGCCAACAGGCCAAAGCCTATGGTGGACCCTTCATGCATCACA
CCCATCCAGCTGGCTCCTATGAAGACAATCGTTAGAGGAAACAAACCCTGCAAGGAAACC
TCCATCAACGGCCTGCTAGAGGATTTTGACAACATCTCGGTGACTCGCTCCAACTCCCTA
AGGAAAGAAAGCCCACCCACCCCAGATCAGGGAGCCTCCAGCCACGGTCCAGGCCACGCG
GAAGAAAATGGCTTCATCACCTTCTCCCAGTATTCCAGCGAATCCGATACTACTGCTGAC
TACACGACCGAAAAGTACAGGGAGAAGAGTCTCTATGGAGATGATCTGGATCCGTATTAT
AGAGGCAGCCACGCAGCCAAGCAAAATGGGCACGTAATGAAAATGAAGCACGGGGAGGCC
TACTATTCTGAGGTGAAGCCTTTGAAATCCGATTTTGCCAGATTTTCTGCCGATTATCAC
TCACATTTGGACTCACTGAGCAAACCAAGTGAATACAGTGACCTCAAGTGGGAGTATCAG
AGAGCCTCGAGTAGCTCCCCTCTGGATTATTCATTCCAATTCACACCTTCTAGAACTGCA
GGGACCAGCGGGTGCTCCAAGGAGAGCCTGGCGTACAGTGAAAGTGAATGGGGACCCAGC
CTGGATGACTATGACAGGAGGCCAAAGTCTTCGTACCTGAATCAGACAAGCCCTCAGCCC
ACCATGCGGCAGAGGTCCAGGTCAGGCTCGGGACTCCAGGAACCGATGATGCCATTTGGA
GCAAGTGCATTTAAAACCCATCCCCAAGGACACTCCTACAACTCCTACACCTACCCTCGC
TTGTCCGAGCCCACAATGTGCATTCCAAAGGTGGATTACGATCGAGCACAGATGGTCCTC
AGCCCTCCACTGTCAGGGTCTGACACCTACCCCAGGGGCCCTGCCAAACTACCTCAAAGT
CAAAGCAAATCGGGCTATTCCTCAAGCAGTCACCAGTACCCGTCTGGGTACCACAAAGCC
ACCTTGTACCATCACCCCTCCCTGCAGAGCAGTTCGCAGTACATCTCCACGGCTTCCTAC
CTGAGCTCCCTCAGCCTCTCATCCAGCACCTACCCGCCGCCCAGCTGGGGCTCCTCCTCC
GACCAGCAGCCCTCCAGGGTGTCCCATGAACAGTTTCGGGCGGCCCTGCAGCTGGTGGTC
AGCCCAGGAGACCCCAGGGAATACTTGGCCAACTTTATCAAAATCGGGGAAGGCTCAACC
GGCATCGTATGCATCGCCACCGAGAAACACACAGGGAAACAAGTTGCAGTGAAGAAAATG
GACCTCCGGAAGCAACAGAGACGAGAACTGCTTTTCAATGAGGTCGTGATCATGCGGGAT
TACCACCATGACAATGTGGTTGACATGTACAGCAGCTACCTTGTCGGCGATGAGCTCTGG
GTGGTCATGGAGTTTCTAGAAGGTGGTGCCTTGACAGACATTGTGACTCACACCAGAATG
AATGAAGAACAGATAGCTACTGTCTGCCTGTCAGTTCTGAGAGCTCTCTCCTACCTTCAT
AACCAAGGAGTGATTCACAGGGACATAAAAAGTGACTCCATCCTCCTGACAAGCGATGGC
CGGATAAAGTTGTCTGATTTTGGTTTCTGTGCTCAAGTTTCCAAAGAGGTGCCGAAGAGG
AAATCATTGGTTGGCACTCCCTACTGGATGGCCCCTGAGGTGATTTCTAGGCTACCTTAT
GGGACAGAGGTGGACATCTGGTCCCTCGGGATCATGGTGATAGAAATGATTGATGGCGAG
CCCCCCTACTTCAATGAGCCTCCCCTCCAGGCGATGCGGAGGATCCGGGACAGTTTACCT
CCAAGAGTGAAGGACCTACACAAGGTTTCTTCAGTGCTCCGGGGATTCCTAGACTTGATG
TTGGTGAGGGAGCCCTCTCAGAGAGCAACAGCCCAGGAACTCCTCGGACATCCATTCTTA
AAACTAGCAGGTCCACCGTCTTGCATCGTCCCCCTCATGAGACAATACAGGCATCACTGA
Chromosome Location
20
Locus
20p12.2
External Identifiers
ResourceLink
UniProtKB IDQ9P286
UniProtKB Entry NamePAK5_HUMAN
HGNC IDHGNC:15916
General References
  1. Pandey A, Dan I, Kristiansen TZ, Watanabe NM, Voldby J, Kajikawa E, Khosravi-Far R, Blagoev B, Mann M: Cloning and characterization of PAK5, a novel member of mammalian p21-activated kinase-II subfamily that is predominantly expressed in brain. Oncogene. 2002 May 30;21(24):3939-48. [Article]
  2. Nagase T, Ishikawa K, Kikuno R, Hirosawa M, Nomura N, Ohara O: Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. DNA Res. 1999 Oct 29;6(5):337-45. [Article]
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
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  5. 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. [Article]
  6. Ching YP, Leong VY, Wong CM, Kung HF: Identification of an autoinhibitory domain of p21-activated protein kinase 5. J Biol Chem. 2003 Sep 5;278(36):33621-4. Epub 2003 Jul 14. [Article]
  7. Cotteret S, Jaffer ZM, Beeser A, Chernoff J: p21-Activated kinase 5 (Pak5) localizes to mitochondria and inhibits apoptosis by phosphorylating BAD. Mol Cell Biol. 2003 Aug;23(16):5526-39. [Article]
  8. Matenia D, Griesshaber B, Li XY, Thiessen A, Johne C, Jiao J, Mandelkow E, Mandelkow EM: PAK5 kinase is an inhibitor of MARK/Par-1, which leads to stable microtubules and dynamic actin. Mol Biol Cell. 2005 Sep;16(9):4410-22. Epub 2005 Jul 12. [Article]
  9. Wu X, Frost JA: Multiple Rho proteins regulate the subcellular targeting of PAK5. Biochem Biophys Res Commun. 2006 Dec 15;351(2):328-35. Epub 2006 Oct 17. [Article]
  10. Cotteret S, Chernoff J: Nucleocytoplasmic shuttling of Pak5 regulates its antiapoptotic properties. Mol Cell Biol. 2006 Apr;26(8):3215-30. [Article]
  11. Wu X, Carr HS, Dan I, Ruvolo PP, Frost JA: p21 activated kinase 5 activates Raf-1 and targets it to mitochondria. J Cell Biochem. 2008 Sep 1;105(1):167-75. doi: 10.1002/jcb.21809. [Article]
  12. Wong LE, Reynolds AB, Dissanayaka NT, Minden A: p120-catenin is a binding partner and substrate for Group B Pak kinases. J Cell Biochem. 2010 Aug 1;110(5):1244-54. doi: 10.1002/jcb.22639. [Article]
  13. Eswaran J, Lee WH, Debreczeni JE, Filippakopoulos P, Turnbull A, Fedorov O, Deacon SW, Peterson JR, Knapp S: Crystal Structures of the p21-activated kinases PAK4, PAK5, and PAK6 reveal catalytic domain plasticity of active group II PAKs. Structure. 2007 Feb;15(2):201-13. [Article]
  14. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB12010Fostamatinibapproved, investigationalunknowninhibitorDetails