PAK6_HUMAN
ID PAK6_HUMAN Reviewed; 681 AA.
AC Q9NQU5; A8K2G2; B3KYB0; G5E9R2;
DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Serine/threonine-protein kinase PAK 6;
DE EC=2.7.11.1;
DE AltName: Full=PAK-5;
DE AltName: Full=p21-activated kinase 6;
DE Short=PAK-6;
GN Name=PAK6; Synonyms=PAK5;
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] (ISOFORM 1), TISSUE SPECIFICITY, SUBCELLULAR
RP LOCATION, AND INTERACTION WITH AR.
RX PubMed=11278661; DOI=10.1074/jbc.m010311200;
RA Yang F., Li X., Sharma M., Zarnegar M., Lim B., Sun Z.;
RT "Androgen receptor specifically interacts with a novel p21-activated
RT kinase, PAK6.";
RL J. Biol. Chem. 276:15345-15353(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Wagner T., Puls A., Frischauf A.M., Hall A.;
RT "Pak5, a new member of the p21-activated kinase family, affects Cdc42
RT signalling to the actin cytoskeleton.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Amygdala, Brain, and Thalamus;
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=16572171; DOI=10.1038/nature04601;
RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K.,
RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K.,
RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N.,
RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S.,
RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K.,
RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J.,
RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E.,
RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B.,
RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R.,
RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B.,
RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S.,
RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.;
RT "Analysis of the DNA sequence and duplication history of human chromosome
RT 15.";
RL Nature 440:671-675(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INTERACTION WITH AR AND ESR1.
RX PubMed=11773441; DOI=10.1210/mend.16.1.0753;
RA Lee S.R., Ramos S.M., Ko A., Masiello D., Swanson K.D., Lu M.L., Balk S.P.;
RT "AR and ER interaction with a p21-activated kinase (PAK6).";
RL Mol. Endocrinol. 16:85-99(2002).
RN [8]
RP FUNCTION IN PHOSPHORYLATION OF AR.
RX PubMed=14573606; DOI=10.1074/jbc.m311145200;
RA Schrantz N., da Silva Correia J., Fowler B., Ge Q., Sun Z., Bokoch G.M.;
RT "Mechanism of p21-activated kinase 6-mediated inhibition of androgen
RT receptor signaling.";
RL J. Biol. Chem. 279:1922-1931(2004).
RN [9]
RP PHOSPHORYLATION BY MAP2K6, AUTOPHOSPHORYLATION, AND MUTAGENESIS OF SER-165;
RP SER-560 AND TYR-566.
RX PubMed=15550393; DOI=10.1074/jbc.m406701200;
RA Kaur R., Liu X., Gjoerup O., Zhang A., Yuan X., Balk S.P., Schneider M.C.,
RA Lu M.L.;
RT "Activation of p21-activated kinase 6 by MAP kinase kinase 6 and p38 MAP
RT kinase.";
RL J. Biol. Chem. 280:3323-3330(2005).
RN [10]
RP INTERACTION WITH IQGAP1 AND PPM1B.
RX PubMed=18642328; DOI=10.1002/pros.20787;
RA Kaur R., Yuan X., Lu M.L., Balk S.P.;
RT "Increased PAK6 expression in prostate cancer and identification of PAK6
RT associated proteins.";
RL Prostate 68:1510-1516(2008).
RN [11]
RP FUNCTION.
RX PubMed=20054820; DOI=10.1002/pros.21114;
RA Zhang M., Siedow M., Saia G., Chakravarti A.;
RT "Inhibition of p21-activated kinase 6 (PAK6) increases radiosensitivity of
RT prostate cancer cells.";
RL Prostate 70:807-816(2010).
RN [12]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 383-681, AND PHOSPHORYLATION AT
RP SER-560.
RA Filippakopoulos P., Berridge G., Bray J., Burgess N., Colebrook S., Das S.,
RA Eswaran J., Gileadi O., Papagrigoriou E., Savitsky P., Smee C.,
RA Turnbull A., Sundstrom M., Arrowsmith C., Weigelt J., Edwards A.,
RA Von Delft F., Knapp S.;
RT "Crystal structure of the human p21-activated kinase 6.";
RL Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases.
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 11-45 IN COMPLEX WITH CDC42.
RG Structural genomics consortium (SGC);
RT "The crystal structure of human CDC42 in complex with the CRIB domain of
RT human p21-activated kinase 6 (PAK6).";
RL Submitted (JAN-2007) to the PDB data bank.
RN [14]
RP VARIANT [LARGE SCALE ANALYSIS] HIS-3.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [15]
RP VARIANTS [LARGE SCALE ANALYSIS] VAL-76; LYS-184; GLU-205; THR-208; MET-210;
RP ARG-215; LEU-337; VAL-376 AND ARG-514.
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 the
CC regulation of gene transcription. The kinase activity is induced by
CC various effectors including AR or MAP2K6/MAPKK6. Phosphorylates the
CC DNA-binding domain of androgen receptor/AR and thereby inhibits AR-
CC mediated transcription. Inhibits also ESR1-mediated transcription. May
CC play a role in cytoskeleton regulation by interacting with IQGAP1. May
CC protect cells from apoptosis through phosphorylation of BAD.
CC {ECO:0000269|PubMed:14573606, ECO:0000269|PubMed:20054820}.
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 (By similarity). Interacts with the androgen receptor AR and
CC the estrogen receptor ESR1. Interacts with IQGAP1 and PPM1B.
CC {ECO:0000250, ECO:0000269|PubMed:11278661, ECO:0000269|PubMed:11773441,
CC ECO:0000269|PubMed:18642328, ECO:0000269|Ref.13}.
CC -!- INTERACTION:
CC Q9NQU5; P60953: CDC42; NbExp=4; IntAct=EBI-1053685, EBI-81752;
CC Q9NQU5; O75031: HSF2BP; NbExp=3; IntAct=EBI-1053685, EBI-7116203;
CC Q9NQU5; Q5S007: LRRK2; NbExp=2; IntAct=EBI-1053685, EBI-5323863;
CC Q9NQU5; Q9H4E5: RHOJ; NbExp=4; IntAct=EBI-1053685, EBI-6285694;
CC Q9NQU5; Q96L33: RHOV; NbExp=3; IntAct=EBI-1053685, EBI-8538631;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Cotranslocates into
CC nucleus with AR in response to androgen induction.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9NQU5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9NQU5-2; Sequence=VSP_056733;
CC -!- TISSUE SPECIFICITY: Selectively expressed in brain and testis, with
CC lower levels in multiple tissues including prostate and breast.
CC {ECO:0000269|PubMed:11278661, ECO:0000269|PubMed:11773441}.
CC -!- PTM: Autophosphorylated. Phosphorylated by MAP2K6//MAPKK6, leading to
CC PAK6 activation. {ECO:0000269|PubMed:15550393, ECO:0000269|Ref.12}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily. {ECO:0000305}.
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DR EMBL; AF276893; AAF82800.1; -; mRNA.
DR EMBL; AJ236915; CAC18720.1; -; mRNA.
DR EMBL; AK131522; BAG54772.1; -; mRNA.
DR EMBL; AK290227; BAF82916.1; -; mRNA.
DR EMBL; AK315813; BAF98704.1; -; mRNA.
DR EMBL; AK315817; BAF98708.1; -; mRNA.
DR EMBL; AC020658; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC025429; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471125; EAW92395.1; -; Genomic_DNA.
DR EMBL; CH471125; EAW92401.1; -; Genomic_DNA.
DR EMBL; BC035596; AAH35596.1; -; mRNA.
DR CCDS; CCDS10054.1; -. [Q9NQU5-1]
DR CCDS; CCDS61590.1; -. [Q9NQU5-2]
DR RefSeq; NP_001122100.1; NM_001128628.2. [Q9NQU5-1]
DR RefSeq; NP_001122101.1; NM_001128629.2. [Q9NQU5-1]
DR RefSeq; NP_001263646.1; NM_001276717.1. [Q9NQU5-1]
DR RefSeq; NP_001263647.1; NM_001276718.1. [Q9NQU5-2]
DR RefSeq; NP_064553.1; NM_020168.5. [Q9NQU5-1]
DR PDB; 2C30; X-ray; 1.60 A; A=383-681.
DR PDB; 2ODB; X-ray; 2.40 A; B=11-45.
DR PDB; 4KS7; X-ray; 1.40 A; A=385-674.
DR PDB; 4KS8; X-ray; 1.95 A; A=385-674.
DR PDB; 6QDR; X-ray; 1.61 A; B=94-104.
DR PDB; 6QDS; X-ray; 1.72 A; B=94-104.
DR PDBsum; 2C30; -.
DR PDBsum; 2ODB; -.
DR PDBsum; 4KS7; -.
DR PDBsum; 4KS8; -.
DR PDBsum; 6QDR; -.
DR PDBsum; 6QDS; -.
DR AlphaFoldDB; Q9NQU5; -.
DR SMR; Q9NQU5; -.
DR BioGRID; 121251; 46.
DR IntAct; Q9NQU5; 55.
DR MINT; Q9NQU5; -.
DR STRING; 9606.ENSP00000406873; -.
DR BindingDB; Q9NQU5; -.
DR ChEMBL; CHEMBL4311; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q9NQU5; -.
DR GuidetoPHARMACOLOGY; 2137; -.
DR iPTMnet; Q9NQU5; -.
DR PhosphoSitePlus; Q9NQU5; -.
DR BioMuta; PAK6; -.
DR DMDM; 23396789; -.
DR EPD; Q9NQU5; -.
DR jPOST; Q9NQU5; -.
DR MassIVE; Q9NQU5; -.
DR MaxQB; Q9NQU5; -.
DR PaxDb; Q9NQU5; -.
DR PeptideAtlas; Q9NQU5; -.
DR PRIDE; Q9NQU5; -.
DR ProteomicsDB; 34018; -.
DR ProteomicsDB; 82189; -. [Q9NQU5-1]
DR Antibodypedia; 10054; 547 antibodies from 39 providers.
DR DNASU; 56924; -.
DR Ensembl; ENST00000260404.8; ENSP00000260404.4; ENSG00000137843.12. [Q9NQU5-1]
DR Ensembl; ENST00000441369.6; ENSP00000406873.1; ENSG00000137843.12. [Q9NQU5-1]
DR Ensembl; ENST00000453867.7; ENSP00000401153.3; ENSG00000137843.12. [Q9NQU5-1]
DR Ensembl; ENST00000455577.6; ENSP00000409465.2; ENSG00000137843.12. [Q9NQU5-2]
DR Ensembl; ENST00000542403.3; ENSP00000439597.2; ENSG00000137843.12. [Q9NQU5-1]
DR Ensembl; ENST00000558658.6; ENSP00000456785.2; ENSG00000137843.12. [Q9NQU5-1]
DR Ensembl; ENST00000560346.5; ENSP00000453858.1; ENSG00000137843.12. [Q9NQU5-1]
DR GeneID; 106821730; -.
DR GeneID; 56924; -.
DR KEGG; hsa:106821730; -.
DR KEGG; hsa:56924; -.
DR MANE-Select; ENST00000560346.6; ENSP00000453858.1; NM_001395430.1; NP_001382359.1.
DR UCSC; uc001zky.5; human. [Q9NQU5-1]
DR CTD; 106821730; -.
DR CTD; 56924; -.
DR DisGeNET; 106821730; -.
DR DisGeNET; 56924; -.
DR GeneCards; PAK6; -.
DR HGNC; HGNC:16061; PAK6.
DR HPA; ENSG00000137843; Tissue enhanced (esophagus, skin).
DR MIM; 608110; gene.
DR neXtProt; NX_Q9NQU5; -.
DR OpenTargets; ENSG00000137843; -.
DR PharmGKB; PA32921; -.
DR VEuPathDB; HostDB:ENSG00000137843; -.
DR eggNOG; KOG0578; Eukaryota.
DR GeneTree; ENSGT00940000156528; -.
DR HOGENOM; CLU_000288_26_6_1; -.
DR InParanoid; Q9NQU5; -.
DR OMA; HRQMPWP; -.
DR PhylomeDB; Q9NQU5; -.
DR TreeFam; TF105352; -.
DR PathwayCommons; Q9NQU5; -.
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 Reactome; R-HSA-9013424; RHOV GTPase cycle.
DR SignaLink; Q9NQU5; -.
DR SIGNOR; Q9NQU5; -.
DR BioGRID-ORCS; 106821730; 1 hit in 19 CRISPR screens.
DR BioGRID-ORCS; 56924; 15 hits in 1104 CRISPR screens.
DR ChiTaRS; PAK6; human.
DR EvolutionaryTrace; Q9NQU5; -.
DR GeneWiki; PAK6; -.
DR Pharos; Q9NQU5; Tchem.
DR PRO; PR:Q9NQU5; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q9NQU5; protein.
DR Bgee; ENSG00000137843; Expressed in gingival epithelium and 144 other tissues.
DR ExpressionAtlas; Q9NQU5; baseline and differential.
DR Genevisible; Q9NQU5; HS.
DR GO; GO:0030054; C:cell junction; IDA:HPA.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0045296; F:cadherin binding; HDA:BHF-UCL.
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: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:0140058; P:neuron projection arborization; IEA:Ensembl.
DR GO; GO:1990138; P:neuron projection extension; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; 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; IPR035066; PAK6.
DR InterPro; IPR033923; PAK_BD.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR PANTHER; PTHR45832:SF3; PTHR45832:SF3; 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; Alternative splicing; ATP-binding; Cytoplasm; Kinase;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..681
FT /note="Serine/threonine-protein kinase PAK 6"
FT /id="PRO_0000086476"
FT DOMAIN 12..25
FT /note="CRIB"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT DOMAIN 407..658
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..30
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 26..406
FT /note="Linker"
FT REGION 149..169
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 200..256
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 268..355
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 275..289
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 290..355
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 526
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 413..421
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 436
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 560
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250"
FT VAR_SEQ 583..627
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056733"
FT VARIANT 3
FT /note="R -> H (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs201346085)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035631"
FT VARIANT 76
FT /note="M -> V (in dbSNP:rs2412504)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_019993"
FT VARIANT 103
FT /note="R -> C (in dbSNP:rs36081263)"
FT /id="VAR_051655"
FT VARIANT 151
FT /note="T -> I (in dbSNP:rs35593179)"
FT /id="VAR_051656"
FT VARIANT 184
FT /note="E -> K (in dbSNP:rs56349744)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040972"
FT VARIANT 205
FT /note="G -> E (in dbSNP:rs55920845)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040973"
FT VARIANT 208
FT /note="P -> T (in dbSNP:rs35501648)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040974"
FT VARIANT 210
FT /note="T -> M (in dbSNP:rs34869667)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040975"
FT VARIANT 215
FT /note="H -> R (in dbSNP:rs3743135)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_019994"
FT VARIANT 337
FT /note="P -> L (in dbSNP:rs3743137)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_019995"
FT VARIANT 376
FT /note="A -> V (in dbSNP:rs55806501)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040976"
FT VARIANT 475
FT /note="E -> K (in dbSNP:rs34445577)"
FT /id="VAR_051657"
FT VARIANT 514
FT /note="L -> R (in a lung small cell carcinoma sample;
FT somatic mutation)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040977"
FT MUTAGEN 165
FT /note="S->A: Almost complete loss of PAK6 activation by
FT MAP2K6/MAPKK6; when associated with F-566."
FT /evidence="ECO:0000269|PubMed:15550393"
FT MUTAGEN 560
FT /note="S->A: Complete loss of PAK6 activation by
FT MAP2K6/MAPKK6; when associated with A-165."
FT /evidence="ECO:0000269|PubMed:15550393"
FT MUTAGEN 566
FT /note="Y->F: Complete loss of PAK6 activation by
FT MAP2K6/MAPKK6; when associated with A-165."
FT /evidence="ECO:0000269|PubMed:15550393"
FT CONFLICT 60
FT /note="T -> A (in Ref. 3; BAG54772)"
FT /evidence="ECO:0000305"
FT CONFLICT 381
FT /note="D -> G (in Ref. 3; BAG54772)"
FT /evidence="ECO:0000305"
FT STRAND 16..27
FT /evidence="ECO:0007829|PDB:2ODB"
FT TURN 28..31
FT /evidence="ECO:0007829|PDB:2ODB"
FT STRAND 32..35
FT /evidence="ECO:0007829|PDB:2ODB"
FT HELIX 38..44
FT /evidence="ECO:0007829|PDB:2ODB"
FT HELIX 387..395
FT /evidence="ECO:0007829|PDB:4KS7"
FT HELIX 404..406
FT /evidence="ECO:0007829|PDB:4KS7"
FT STRAND 407..416
FT /evidence="ECO:0007829|PDB:4KS7"
FT STRAND 419..426
FT /evidence="ECO:0007829|PDB:4KS7"
FT TURN 427..429
FT /evidence="ECO:0007829|PDB:4KS7"
FT STRAND 432..439
FT /evidence="ECO:0007829|PDB:4KS7"
FT TURN 440..442
FT /evidence="ECO:0007829|PDB:2C30"
FT HELIX 446..448
FT /evidence="ECO:0007829|PDB:4KS7"
FT HELIX 449..458
FT /evidence="ECO:0007829|PDB:4KS7"
FT STRAND 467..473
FT /evidence="ECO:0007829|PDB:4KS7"
FT STRAND 476..481
FT /evidence="ECO:0007829|PDB:4KS7"
FT HELIX 489..493
FT /evidence="ECO:0007829|PDB:4KS7"
FT HELIX 500..519
FT /evidence="ECO:0007829|PDB:4KS7"
FT HELIX 529..531
FT /evidence="ECO:0007829|PDB:4KS7"
FT STRAND 532..534
FT /evidence="ECO:0007829|PDB:4KS7"
FT STRAND 540..542
FT /evidence="ECO:0007829|PDB:4KS7"
FT HELIX 545..547
FT /evidence="ECO:0007829|PDB:4KS7"
FT STRAND 553..555
FT /evidence="ECO:0007829|PDB:4KS7"
FT HELIX 565..567
FT /evidence="ECO:0007829|PDB:4KS7"
FT HELIX 570..573
FT /evidence="ECO:0007829|PDB:4KS7"
FT HELIX 581..596
FT /evidence="ECO:0007829|PDB:4KS7"
FT TURN 600..603
FT /evidence="ECO:0007829|PDB:4KS7"
FT HELIX 606..615
FT /evidence="ECO:0007829|PDB:4KS7"
FT HELIX 624..626
FT /evidence="ECO:0007829|PDB:4KS7"
FT HELIX 629..638
FT /evidence="ECO:0007829|PDB:4KS7"
FT TURN 643..645
FT /evidence="ECO:0007829|PDB:4KS7"
FT HELIX 649..653
FT /evidence="ECO:0007829|PDB:4KS7"
FT HELIX 656..660
FT /evidence="ECO:0007829|PDB:4KS7"
FT HELIX 664..670
FT /evidence="ECO:0007829|PDB:4KS7"
SQ SEQUENCE 681 AA; 74869 MW; F20A4FA257649BB9 CRC64;
MFRKKKKKRP EISAPQNFQH RVHTSFDPKE GKFVGLPPQW QNILDTLRRP KPVVDPSRIT
RVQLQPMKTV VRGSAMPVDG YISGLLNDIQ KLSVISSNTL RGRSPTSRRR AQSLGLLGDE
HWATDPDMYL QSPQSERTDP HGLYLSCNGG TPAGHKQMPW PEPQSPRVLP NGLAAKAQSL
GPAEFQGASQ RCLQLGACLQ SSPPGASPPT GTNRHGMKAA KHGSEEARPQ SCLVGSATGR
PGGEGSPSPK TRESSLKRRL FRSMFLSTAA TAPPSSSKPG PPPQSKPNSS FRPPQKDNPP
SLVAKAQSLP SDQPVGTFSP LTTSDTSSPQ KSLRTAPATG QLPGRSSPAG SPRTWHAQIS
TSNLYLPQDP TVAKGALAGE DTGVVTHEQF KAALRMVVDQ GDPRLLLDSY VKIGEGSTGI
VCLAREKHSG RQVAVKMMDL RKQQRRELLF NEVVIMRDYQ HFNVVEMYKS YLVGEELWVL
MEFLQGGALT DIVSQVRLNE EQIATVCEAV LQALAYLHAQ GVIHRDIKSD SILLTLDGRV
KLSDFGFCAQ ISKDVPKRKS LVGTPYWMAP EVISRSLYAT EVDIWSLGIM VIEMVDGEPP
YFSDSPVQAM KRLRDSPPPK LKNSHKVSPV LRDFLERMLV RDPQERATAQ ELLDHPFLLQ
TGLPECLVPL IQLYRKQTST C
