PAK5_HUMAN
ID PAK5_HUMAN Reviewed; 719 AA.
AC Q9P286; A8K5T6; D3DW14; Q5W115; Q8TB93; Q9BX09; Q9ULF6;
DT 24-JAN-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 210.
DE RecName: Full=Serine/threonine-protein kinase PAK 5 {ECO:0000305};
DE EC=2.7.11.1;
DE AltName: Full=p21-activated kinase 5;
DE Short=PAK-5;
DE AltName: Full=p21-activated kinase 7;
DE Short=PAK-7;
GN Name=PAK5 {ECO:0000312|HGNC:HGNC:15916}; Synonyms=KIAA1264, PAK7;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Brain;
RX PubMed=12032833; DOI=10.1038/sj.onc.1205478;
RA Pandey A., Dan I., Kristiansen T.Z., Watanabe N.M., Voldby J., Kajikawa E.,
RA Khosravi-Far R., Blagoev B., Mann M.;
RT "Cloning and characterization of PAK5, a novel member of mammalian p21-
RT activated kinase-II subfamily that is predominantly expressed in brain.";
RL Oncogene 21:3939-3948(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=10574462; DOI=10.1093/dnares/6.5.337;
RA Nagase T., Ishikawa K., Kikuno R., Hirosawa M., Nomura N., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XV. The
RT complete sequences of 100 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 6:337-345(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ASN-511.
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP DOMAIN, AND MUTAGENESIS OF 19-HIS--HIS-22.
RX PubMed=12860998; DOI=10.1074/jbc.c300234200;
RA Ching Y.P., Leong V.Y., Wong C.M., Kung H.F.;
RT "Identification of an autoinhibitory domain of p21-activated protein kinase
RT 5.";
RL J. Biol. Chem. 278:33621-33624(2003).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=12897128; DOI=10.1128/mcb.23.16.5526-5539.2003;
RA Cotteret S., Jaffer Z.M., Beeser A., Chernoff J.;
RT "p21-Activated kinase 5 (Pak5) localizes to mitochondria and inhibits
RT apoptosis by phosphorylating BAD.";
RL Mol. Cell. Biol. 23:5526-5539(2003).
RN [9]
RP FUNCTION, AND INTERACTION WITH MARK2.
RX PubMed=16014608; DOI=10.1091/mbc.e05-01-0081;
RA Matenia D., Griesshaber B., Li X.Y., Thiessen A., Johne C., Jiao J.,
RA Mandelkow E., Mandelkow E.M.;
RT "PAK5 kinase is an inhibitor of MARK/Par-1, which leads to stable
RT microtubules and dynamic actin.";
RL Mol. Biol. Cell 16:4410-4422(2005).
RN [10]
RP INTERACTION WITH RHOD AND RHOH.
RX PubMed=17064668; DOI=10.1016/j.bbrc.2006.09.172;
RA Wu X., Frost J.A.;
RT "Multiple Rho proteins regulate the subcellular targeting of PAK5.";
RL Biochem. Biophys. Res. Commun. 351:328-335(2006).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=16581795; DOI=10.1128/mcb.26.8.3215-3230.2006;
RA Cotteret S., Chernoff J.;
RT "Nucleocytoplasmic shuttling of Pak5 regulates its antiapoptotic
RT properties.";
RL Mol. Cell. Biol. 26:3215-3230(2006).
RN [12]
RP FUNCTION IN PHOSPHORYLATION OF RAF1.
RX PubMed=18465753; DOI=10.1002/jcb.21809;
RA Wu X., Carr H.S., Dan I., Ruvolo P.P., Frost J.A.;
RT "p21 activated kinase 5 activates Raf-1 and targets it to mitochondria.";
RL J. Cell. Biochem. 105:167-175(2008).
RN [13]
RP FUNCTION IN PHOSPHORYLATION OF CTNND1.
RX PubMed=20564219; DOI=10.1002/jcb.22639;
RA Wong L.E., Reynolds A.B., Dissanayaka N.T., Minden A.;
RT "p120-catenin is a binding partner and substrate for Group B Pak kinases.";
RL J. Cell. Biochem. 110:1244-1254(2010).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 425-719.
RX PubMed=17292838; DOI=10.1016/j.str.2007.01.001;
RA Eswaran J., Lee W.H., Debreczeni J.E., Filippakopoulos P., Turnbull A.,
RA Fedorov O., Deacon S.W., Peterson J.R., Knapp S.;
RT "Crystal Structures of the p21-activated kinases PAK4, PAK5, and PAK6
RT reveal catalytic domain plasticity of active group II PAKs.";
RL Structure 15:201-213(2007).
RN [15]
RP VARIANTS [LARGE SCALE ANALYSIS] ASP-118; ALA-187; PRO-312; PRO-335;
RP ASN-511; ASN-538; SER-555; ILE-604 AND SER-704.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Serine/threonine protein kinase that plays a role in a
CC variety of different signaling pathways including cytoskeleton
CC regulation, cell migration, proliferation or cell survival. Activation
CC by various effectors including growth factor receptors or active CDC42
CC and RAC1 results in a conformational change and a subsequent
CC autophosphorylation on several serine and/or threonine residues.
CC Phosphorylates the proto-oncogene RAF1 and stimulates its kinase
CC activity. Promotes cell survival by phosphorylating the BCL2 antagonist
CC of cell death BAD. Phosphorylates CTNND1, probably to regulate
CC cytoskeletal organization and cell morphology. Keeps microtubules
CC stable through MARK2 inhibition and destabilizes the F-actin network
CC leading to the disappearance of stress fibers and focal adhesions.
CC {ECO:0000269|PubMed:12897128, ECO:0000269|PubMed:16014608,
CC ECO:0000269|PubMed:16581795, ECO:0000269|PubMed:18465753,
CC ECO:0000269|PubMed:20564219}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- SUBUNIT: Interacts tightly with GTP-bound but not GDP-bound CDC42/p21
CC and RAC1. Interacts with MARK2, leading to inhibit MARK2 independently
CC of kinase activity. Interacts with RHOD and RHOH.
CC {ECO:0000269|PubMed:16014608, ECO:0000269|PubMed:17064668}.
CC -!- INTERACTION:
CC Q9P286; Q8IW93: ARHGEF19; NbExp=3; IntAct=EBI-741896, EBI-7799822;
CC Q9P286; Q9H6L4: ARMC7; NbExp=3; IntAct=EBI-741896, EBI-742909;
CC Q9P286; Q8N5M1: ATPAF2; NbExp=7; IntAct=EBI-741896, EBI-1166928;
CC Q9P286; Q9H257: CARD9; NbExp=5; IntAct=EBI-741896, EBI-751319;
CC Q9P286; Q9H257-2: CARD9; NbExp=3; IntAct=EBI-741896, EBI-11530605;
CC Q9P286; Q8NEC5: CATSPER1; NbExp=3; IntAct=EBI-741896, EBI-744545;
CC Q9P286; Q2TAC2-2: CCDC57; NbExp=3; IntAct=EBI-741896, EBI-10961624;
CC Q9P286; P51959: CCNG1; NbExp=4; IntAct=EBI-741896, EBI-3905829;
CC Q9P286; P60953: CDC42; NbExp=5; IntAct=EBI-741896, EBI-81752;
CC Q9P286; Q96SW2: CRBN; NbExp=4; IntAct=EBI-741896, EBI-2510250;
CC Q9P286; P48730: CSNK1D; NbExp=3; IntAct=EBI-741896, EBI-751621;
CC Q9P286; P26196: DDX6; NbExp=3; IntAct=EBI-741896, EBI-351257;
CC Q9P286; P50402: EMD; NbExp=3; IntAct=EBI-741896, EBI-489887;
CC Q9P286; Q9H0I2: ENKD1; NbExp=3; IntAct=EBI-741896, EBI-744099;
CC Q9P286; Q9Y3B2: EXOSC1; NbExp=3; IntAct=EBI-741896, EBI-371892;
CC Q9P286; Q96CN9: GCC1; NbExp=3; IntAct=EBI-741896, EBI-746252;
CC Q9P286; A0A024R8L2: hCG_1987119; NbExp=3; IntAct=EBI-741896, EBI-14103818;
CC Q9P286; P42858: HTT; NbExp=3; IntAct=EBI-741896, EBI-466029;
CC Q9P286; Q96EL1: INKA1; NbExp=5; IntAct=EBI-741896, EBI-10285157;
CC Q9P286; Q96BZ8: LENG1; NbExp=3; IntAct=EBI-741896, EBI-726510;
CC Q9P286; Q8TBB1: LNX1; NbExp=3; IntAct=EBI-741896, EBI-739832;
CC Q9P286; P07196: NEFL; NbExp=3; IntAct=EBI-741896, EBI-475646;
CC Q9P286; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-741896, EBI-741158;
CC Q9P286; P16284: PECAM1; NbExp=3; IntAct=EBI-741896, EBI-716404;
CC Q9P286; Q8WWY3: PRPF31; NbExp=6; IntAct=EBI-741896, EBI-1567797;
CC Q9P286; Q92530: PSMF1; NbExp=3; IntAct=EBI-741896, EBI-945916;
CC Q9P286; Q16825: PTPN21; NbExp=3; IntAct=EBI-741896, EBI-2860264;
CC Q9P286; Q9H4E5: RHOJ; NbExp=3; IntAct=EBI-741896, EBI-6285694;
CC Q9P286; O60504: SORBS3; NbExp=3; IntAct=EBI-741896, EBI-741237;
CC Q9P286; Q9BZW7: TSGA10; NbExp=3; IntAct=EBI-741896, EBI-744794;
CC Q9P286; Q9UBK9: UXT; NbExp=4; IntAct=EBI-741896, EBI-357355;
CC Q9P286; O76024: WFS1; NbExp=3; IntAct=EBI-741896, EBI-720609;
CC -!- SUBCELLULAR LOCATION: Mitochondrion. Cytoplasm. Nucleus. Note=Shuttles
CC between the nucleus and the mitochondria, and mitochondrial
CC localization is essential for the role in cell survival.
CC -!- TISSUE SPECIFICITY: Predominantly expressed in brain.
CC -!- DOMAIN: An autoinhibitory domain is present in the N-terminal region of
CC the protein. {ECO:0000269|PubMed:12860998}.
CC -!- PTM: Autophosphorylated when activated by CDC42/p21.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA86578.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB040812; BAA94194.1; -; mRNA.
DR EMBL; AB033090; BAA86578.1; ALT_INIT; mRNA.
DR EMBL; AK291401; BAF84090.1; -; mRNA.
DR EMBL; AL031652; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL135935; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL353612; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471133; EAX10358.1; -; Genomic_DNA.
DR EMBL; CH471133; EAX10359.1; -; Genomic_DNA.
DR EMBL; CH471133; EAX10360.1; -; Genomic_DNA.
DR EMBL; BC024179; AAH24179.1; -; mRNA.
DR CCDS; CCDS13107.1; -.
DR RefSeq; NP_065074.1; NM_020341.3.
DR RefSeq; NP_817127.1; NM_177990.2.
DR RefSeq; XP_016883449.1; XM_017027960.1.
DR RefSeq; XP_016883450.1; XM_017027961.1.
DR RefSeq; XP_016883451.1; XM_017027962.1.
DR RefSeq; XP_016883452.1; XM_017027963.1.
DR RefSeq; XP_016883453.1; XM_017027964.1.
DR RefSeq; XP_016883454.1; XM_017027965.1.
DR PDB; 2F57; X-ray; 1.80 A; A/B=425-719.
DR PDBsum; 2F57; -.
DR AlphaFoldDB; Q9P286; -.
DR SMR; Q9P286; -.
DR BioGRID; 121402; 94.
DR IntAct; Q9P286; 104.
DR MINT; Q9P286; -.
DR STRING; 9606.ENSP00000367686; -.
DR BindingDB; Q9P286; -.
DR ChEMBL; CHEMBL4524; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q9P286; -.
DR GuidetoPHARMACOLOGY; 2138; -.
DR iPTMnet; Q9P286; -.
DR PhosphoSitePlus; Q9P286; -.
DR BioMuta; PAK5; -.
DR DMDM; 12585290; -.
DR EPD; Q9P286; -.
DR jPOST; Q9P286; -.
DR MassIVE; Q9P286; -.
DR MaxQB; Q9P286; -.
DR PaxDb; Q9P286; -.
DR PeptideAtlas; Q9P286; -.
DR PRIDE; Q9P286; -.
DR ProteomicsDB; 83751; -.
DR Antibodypedia; 8792; 378 antibodies from 39 providers.
DR DNASU; 57144; -.
DR Ensembl; ENST00000353224.10; ENSP00000322957.5; ENSG00000101349.17.
DR Ensembl; ENST00000378423.5; ENSP00000367679.1; ENSG00000101349.17.
DR Ensembl; ENST00000378429.3; ENSP00000367686.3; ENSG00000101349.17.
DR GeneID; 57144; -.
DR KEGG; hsa:57144; -.
DR MANE-Select; ENST00000353224.10; ENSP00000322957.5; NM_177990.4; NP_817127.1.
DR UCSC; uc002wnj.3; human.
DR CTD; 57144; -.
DR DisGeNET; 57144; -.
DR GeneCards; PAK5; -.
DR HGNC; HGNC:15916; PAK5.
DR HPA; ENSG00000101349; Group enriched (brain, retina).
DR MIM; 608038; gene.
DR neXtProt; NX_Q9P286; -.
DR OpenTargets; ENSG00000101349; -.
DR PharmGKB; PA32922; -.
DR VEuPathDB; HostDB:ENSG00000101349; -.
DR eggNOG; KOG0578; Eukaryota.
DR GeneTree; ENSGT00940000158656; -.
DR HOGENOM; CLU_000288_26_6_1; -.
DR InParanoid; Q9P286; -.
DR OMA; VDYHAHL; -.
DR OrthoDB; 757766at2759; -.
DR PhylomeDB; Q9P286; -.
DR TreeFam; TF105352; -.
DR BRENDA; 2.7.11.1; 2681.
DR BRENDA; 2.7.12.2; 2681.
DR PathwayCommons; Q9P286; -.
DR Reactome; R-HSA-428540; Activation of RAC1.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR Reactome; R-HSA-9013405; RHOD GTPase cycle.
DR Reactome; R-HSA-9013407; RHOH GTPase cycle.
DR SignaLink; Q9P286; -.
DR SIGNOR; Q9P286; -.
DR BioGRID-ORCS; 57144; 9 hits in 1105 CRISPR screens.
DR ChiTaRS; PAK5; human.
DR EvolutionaryTrace; Q9P286; -.
DR GeneWiki; PAK7; -.
DR GenomeRNAi; 57144; -.
DR Pharos; Q9P286; Tchem.
DR PRO; PR:Q9P286; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9P286; protein.
DR Bgee; ENSG00000101349; Expressed in cortical plate and 93 other tissues.
DR Genevisible; Q9P286; HS.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR GO; GO:0045202; C:synapse; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; TAS:UniProtKB.
DR GO; GO:0016477; P:cell migration; TAS:UniProtKB.
DR GO; GO:0008283; P:cell population proliferation; TAS:UniProtKB.
DR GO; GO:0007010; P:cytoskeleton organization; TAS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0007612; P:learning; IEA:Ensembl.
DR GO; GO:0007626; P:locomotory behavior; IEA:Ensembl.
DR GO; GO:0007613; P:memory; IEA:Ensembl.
DR GO; GO:2001237; P:negative regulation of extrinsic apoptotic signaling pathway; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0001558; P:regulation of cell growth; TAS:UniProtKB.
DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; TAS:UniProtKB.
DR CDD; cd01093; CRIB_PAK_like; 1.
DR Gene3D; 3.90.810.10; -; 1.
DR InterPro; IPR000095; CRIB_dom.
DR InterPro; IPR036936; CRIB_dom_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR028754; PAK5.
DR InterPro; IPR033923; PAK_BD.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR PANTHER; PTHR45832:SF4; PTHR45832:SF4; 1.
DR Pfam; PF00786; PBD; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00285; PBD; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50108; CRIB; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Apoptosis; ATP-binding; Cytoplasm; Kinase; Mitochondrion;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..719
FT /note="Serine/threonine-protein kinase PAK 5"
FT /id="PRO_0000086477"
FT DOMAIN 11..24
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT DOMAIN 449..700
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..29
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 25..448
FT /note="Linker"
FT REGION 97..123
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 256..299
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 340..373
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..15
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 97..111
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 270..291
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 354..373
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 568
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 455..463
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 478
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 104
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8C015"
FT MOD_RES 107
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q8C015"
FT VARIANT 118
FT /note="G -> D (in dbSNP:rs55923311)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040978"
FT VARIANT 187
FT /note="P -> A (in dbSNP:rs34280805)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040979"
FT VARIANT 312
FT /note="S -> P (in a colorectal adenocarcinoma sample;
FT somatic mutation; dbSNP:rs952665081)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040980"
FT VARIANT 335
FT /note="R -> P (in dbSNP:rs11700112)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040981"
FT VARIANT 511
FT /note="S -> N (in dbSNP:rs2297345)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:17344846"
FT /id="VAR_021865"
FT VARIANT 538
FT /note="T -> N (in a lung adenocarcinoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040982"
FT VARIANT 555
FT /note="A -> S (in dbSNP:rs34102290)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040983"
FT VARIANT 604
FT /note="V -> I (in a metastatic melanoma sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040984"
FT VARIANT 704
FT /note="G -> S (in a metastatic melanoma sample; somatic
FT mutation; dbSNP:rs1484691555)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040985"
FT MUTAGEN 19..22
FT /note="HRVH->LRVL: Complete loss of CDC42 binding and
FT CDC42-mediated autophosphorylation."
FT /evidence="ECO:0000269|PubMed:12860998"
FT CONFLICT 27
FT /note="P -> A (in Ref. 6; AAH24179)"
FT /evidence="ECO:0000305"
FT CONFLICT 403
FT /note="S -> Y (in Ref. 6; AAH24179)"
FT /evidence="ECO:0000305"
FT HELIX 429..437
FT /evidence="ECO:0007829|PDB:2F57"
FT HELIX 445..447
FT /evidence="ECO:0007829|PDB:2F57"
FT STRAND 449..457
FT /evidence="ECO:0007829|PDB:2F57"
FT STRAND 459..468
FT /evidence="ECO:0007829|PDB:2F57"
FT TURN 469..471
FT /evidence="ECO:0007829|PDB:2F57"
FT STRAND 474..481
FT /evidence="ECO:0007829|PDB:2F57"
FT HELIX 482..484
FT /evidence="ECO:0007829|PDB:2F57"
FT HELIX 488..500
FT /evidence="ECO:0007829|PDB:2F57"
FT STRAND 509..515
FT /evidence="ECO:0007829|PDB:2F57"
FT STRAND 518..524
FT /evidence="ECO:0007829|PDB:2F57"
FT HELIX 531..535
FT /evidence="ECO:0007829|PDB:2F57"
FT HELIX 542..561
FT /evidence="ECO:0007829|PDB:2F57"
FT HELIX 571..573
FT /evidence="ECO:0007829|PDB:2F57"
FT STRAND 574..576
FT /evidence="ECO:0007829|PDB:2F57"
FT STRAND 582..584
FT /evidence="ECO:0007829|PDB:2F57"
FT STRAND 595..597
FT /evidence="ECO:0007829|PDB:2F57"
FT HELIX 607..609
FT /evidence="ECO:0007829|PDB:2F57"
FT HELIX 612..615
FT /evidence="ECO:0007829|PDB:2F57"
FT HELIX 623..638
FT /evidence="ECO:0007829|PDB:2F57"
FT TURN 642..645
FT /evidence="ECO:0007829|PDB:2F57"
FT HELIX 648..657
FT /evidence="ECO:0007829|PDB:2F57"
FT HELIX 666..668
FT /evidence="ECO:0007829|PDB:2F57"
FT HELIX 671..680
FT /evidence="ECO:0007829|PDB:2F57"
FT HELIX 685..687
FT /evidence="ECO:0007829|PDB:2F57"
FT HELIX 691..695
FT /evidence="ECO:0007829|PDB:2F57"
FT HELIX 698..702
FT /evidence="ECO:0007829|PDB:2F57"
FT HELIX 706..708
FT /evidence="ECO:0007829|PDB:2F57"
FT HELIX 710..712
FT /evidence="ECO:0007829|PDB:2F57"
SQ SEQUENCE 719 AA; 80745 MW; 07A12B1EEC4E2A02 CRC64;
MFGKKKKKIE ISGPSNFEHR VHTGFDPQEQ KFTGLPQQWH SLLADTANRP KPMVDPSCIT
PIQLAPMKTI VRGNKPCKET SINGLLEDFD NISVTRSNSL RKESPPTPDQ GASSHGPGHA
EENGFITFSQ YSSESDTTAD YTTEKYREKS LYGDDLDPYY RGSHAAKQNG HVMKMKHGEA
YYSEVKPLKS DFARFSADYH SHLDSLSKPS EYSDLKWEYQ RASSSSPLDY SFQFTPSRTA
GTSGCSKESL AYSESEWGPS LDDYDRRPKS SYLNQTSPQP TMRQRSRSGS GLQEPMMPFG
ASAFKTHPQG HSYNSYTYPR LSEPTMCIPK VDYDRAQMVL SPPLSGSDTY PRGPAKLPQS
QSKSGYSSSS HQYPSGYHKA TLYHHPSLQS SSQYISTASY LSSLSLSSST YPPPSWGSSS
DQQPSRVSHE QFRAALQLVV SPGDPREYLA NFIKIGEGST GIVCIATEKH TGKQVAVKKM
DLRKQQRREL LFNEVVIMRD YHHDNVVDMY SSYLVGDELW VVMEFLEGGA LTDIVTHTRM
NEEQIATVCL SVLRALSYLH NQGVIHRDIK SDSILLTSDG RIKLSDFGFC AQVSKEVPKR
KSLVGTPYWM APEVISRLPY GTEVDIWSLG IMVIEMIDGE PPYFNEPPLQ AMRRIRDSLP
PRVKDLHKVS SVLRGFLDLM LVREPSQRAT AQELLGHPFL KLAGPPSCIV PLMRQYRHH
