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 27-MAR-2024, entry version 206. 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 Q9NQU5; P62258: YWHAE; NbExp=4; IntAct=EBI-1053685, EBI-356498; 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}. 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; 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; 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; 75. DR IntAct; Q9NQU5; 56. DR MINT; Q9NQU5; -. DR STRING; 9606.ENSP00000453858; -. 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; 9606-ENSP00000406873; -. DR PeptideAtlas; Q9NQU5; -. DR ProteomicsDB; 34018; -. DR ProteomicsDB; 82189; -. [Q9NQU5-1] DR Antibodypedia; 10054; 617 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; ENST00000560346.6; 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 AGR; HGNC:16061; -. DR AGR; HGNC:52276; -. 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 (brain, 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; ARRQTMW; -. DR OrthoDB; 460351at2759; -. 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 22 CRISPR screens. DR BioGRID-ORCS; 56924; 21 hits in 1182 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 146 other cell types or tissues. DR ExpressionAtlas; Q9NQU5; baseline and differential. 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:0014069; C:postsynaptic density; IEA:Ensembl. 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:0016310; P:phosphorylation; IEA:UniProtKB-KW. DR GO; GO:0006355; P:regulation of DNA-templated transcription; TAS:UniProtKB. DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central. DR CDD; cd01093; CRIB_PAK_like; 1. DR CDD; cd06659; STKc_PAK6; 1. DR Gene3D; 3.90.810.10; CRIB domain; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR000095; CRIB_dom. DR InterPro; IPR036936; CRIB_dom_sf. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR033923; PAK_BD. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR035066; STKc_PAK6. DR PANTHER; PTHR48015; SERINE/THREONINE-PROTEIN KINASE TAO; 1. DR PANTHER; PTHR48015:SF19; SERINE_THREONINE-PROTEIN KINASE PAK 6; 1. DR Pfam; PF00786; PBD; 1. DR Pfam; PF00069; Pkinase; 1. DR SMART; SM00285; PBD; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS50108; CRIB; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR Genevisible; Q9NQU5; HS. 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 //