ID   PAK6_MOUSE              Reviewed;         682 AA.
AC   Q3ULB5; Q3TY26;
DT   20-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT   11-OCT-2005, sequence version 1.
DT   27-MAR-2024, entry version 143.
DE   RecName: Full=Serine/threonine-protein kinase PAK 6;
DE            EC=2.7.11.1;
DE   AltName: Full=p21-activated kinase 6;
DE            Short=PAK-6;
GN   Name=Pak6;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Visual cortex;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
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 (By
CC       similarity). {ECO:0000250}.
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 the androgen receptor AR. Interacts with
CC       IQGAP1 and PPM1B (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC       Note=Cotranslocates into nucleus with AR in response to androgen
CC       induction. {ECO:0000250}.
CC   -!- PTM: Autophosphorylated. Phosphorylated by MAP2K6/MAPKK6, leading to
CC       PAK6 activation (By similarity). {ECO:0000250}.
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; AK145601; BAE26534.1; -; mRNA.
DR   EMBL; AK158913; BAE34725.1; -; mRNA.
DR   EMBL; AK158944; BAE34737.1; -; mRNA.
DR   EMBL; AL845470; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS16580.1; -.
DR   RefSeq; NP_001028426.2; NM_001033254.3.
DR   RefSeq; NP_001139326.1; NM_001145854.1.
DR   RefSeq; XP_011237721.1; XM_011239419.1.
DR   RefSeq; XP_011237722.1; XM_011239420.2.
DR   AlphaFoldDB; Q3ULB5; -.
DR   SMR; Q3ULB5; -.
DR   BioGRID; 229506; 2.
DR   STRING; 10090.ENSMUSP00000097153; -.
DR   iPTMnet; Q3ULB5; -.
DR   PhosphoSitePlus; Q3ULB5; -.
DR   MaxQB; Q3ULB5; -.
DR   PaxDb; 10090-ENSMUSP00000097153; -.
DR   ProteomicsDB; 294152; -.
DR   Antibodypedia; 10054; 617 antibodies from 39 providers.
DR   DNASU; 214230; -.
DR   Ensembl; ENSMUST00000099557.10; ENSMUSP00000097153.4; ENSMUSG00000074923.11.
DR   Ensembl; ENSMUST00000110853.8; ENSMUSP00000106477.2; ENSMUSG00000074923.11.
DR   GeneID; 214230; -.
DR   KEGG; mmu:214230; -.
DR   UCSC; uc008lsf.2; mouse.
DR   AGR; MGI:2679420; -.
DR   CTD; 56924; -.
DR   MGI; MGI:2679420; Pak6.
DR   VEuPathDB; HostDB:ENSMUSG00000074923; -.
DR   eggNOG; KOG0578; Eukaryota.
DR   GeneTree; ENSGT00940000156528; -.
DR   HOGENOM; CLU_000288_26_6_1; -.
DR   InParanoid; Q3ULB5; -.
DR   OMA; ARRQTMW; -.
DR   OrthoDB; 460351at2759; -.
DR   PhylomeDB; Q3ULB5; -.
DR   TreeFam; TF105352; -.
DR   Reactome; R-MMU-9013149; RAC1 GTPase cycle.
DR   Reactome; R-MMU-9013405; RHOD GTPase cycle.
DR   Reactome; R-MMU-9013407; RHOH GTPase cycle.
DR   Reactome; R-MMU-9013424; RHOV GTPase cycle.
DR   BioGRID-ORCS; 214230; 2 hits in 80 CRISPR screens.
DR   PRO; PR:Q3ULB5; -.
DR   Proteomes; UP000000589; Chromosome 2.
DR   RNAct; Q3ULB5; Protein.
DR   Bgee; ENSMUSG00000074923; Expressed in embryonic brain and 122 other cell types or tissues.
DR   GO; GO:0030054; C:cell junction; ISO:MGI.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0001650; C:fibrillar center; ISO:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0014069; C:postsynaptic density; IDA:SynGO.
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:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR   GO; GO:0007612; P:learning; IGI:MGI.
DR   GO; GO:0007626; P:locomotory behavior; IGI:MGI.
DR   GO; GO:0007613; P:memory; IGI:MGI.
DR   GO; GO:0140058; P:neuron projection arborization; IMP:MGI.
DR   GO; GO:1990138; P:neuron projection extension; IMP:MGI.
DR   GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
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; Q3ULB5; MM.
PE   2: Evidence at transcript level;
KW   ATP-binding; Cytoplasm; Kinase; Nucleotide-binding; Nucleus;
KW   Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW   Transferase.
FT   CHAIN           1..682
FT                   /note="Serine/threonine-protein kinase PAK 6"
FT                   /id="PRO_0000278117"
FT   DOMAIN          12..25
FT                   /note="CRIB"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00057"
FT   DOMAIN          408..659
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..407
FT                   /note="Linker"
FT                   /evidence="ECO:0000250"
FT   REGION          132..170
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          270..367
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        270..335
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        352..367
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        527
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         414..422
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   BINDING         437
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT   MOD_RES         561
FT                   /note="Phosphoserine; by autocatalysis"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        667
FT                   /note="C -> R (in Ref. 1; BAE34737/BAE34725)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   682 AA;  74867 MW;  F9D415D49A130C0C CRC64;
     MFRKKKKKRP EISAPQNFQH RVHTSFDPKE GKFVGLPPQW QNILDTLRRP KPVVDPSRIT
     RVQLQPMKTV VRGSSVPTEG YISGLLNDIQ KLSVISSNTL RGRSPTSRRR AQSLGLLGDD
     QWAADPDMYL QSPQSEHTDP HGLYLSCNGG TPAGHRQVPW PEPQSPQALP NGMAAKAQSL
     GPAEFQGASQ RCLQQLGACL QSSPPGTSPP MATGRRGVKV AKHSSEEARP QSCLVGSAIG
     RPGGEGSPSP KNQESSLKHR LFRSMFLSTP ATGAASSSKP VPLPQNKPNS AFRPPQKDSS
     SNLVAKAQSL PSEQPMGTFS PLTTSDTSSP QKSLRTAPAA GPLPGRSSPA GSPRTRHAQI
     STSNLYLPQD PTVAKGALGG EDTGIVTHEQ FKAALRMVVD QGDPRLLLDS YVKIGEGSTG
     IVCLAREKHS GRQVAVKMMD LRKQQRRELL FNEVVIMRDY QHLNVVEMYK SYLVGEELWV
     LMEFLQGGAL TDIISQVRLN EEQIATVCEA VLQALAYLHA QGVIHRDIKS DSILLTLDGR
     VKLSDFGFCA QISKDVPKRK SLVGTPYWMA PEVISRSLYA TEVDIWSLGI MVIEMVDGEP
     PYFSDSPVQA MKRLRDSAPP KLKNSYKVSP VLRDFLDRML VREPQERATA QELLDHPFLL
     QTGLPECLVP LIQLYRKQTS TC
//