PAK6_MOUSE
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 03-AUG-2022, entry version 134.
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; 1.
DR STRING; 10090.ENSMUSP00000097153; -.
DR iPTMnet; Q3ULB5; -.
DR PhosphoSitePlus; Q3ULB5; -.
DR MaxQB; Q3ULB5; -.
DR PaxDb; Q3ULB5; -.
DR PRIDE; Q3ULB5; -.
DR ProteomicsDB; 294152; -.
DR Antibodypedia; 10054; 547 antibodies from 39 providers.
DR DNASU; 214230; -.
DR Ensembl; ENSMUST00000099557; ENSMUSP00000097153; ENSMUSG00000074923.
DR Ensembl; ENSMUST00000110853; ENSMUSP00000106477; ENSMUSG00000074923.
DR GeneID; 214230; -.
DR KEGG; mmu:214230; -.
DR UCSC; uc008lsf.2; mouse.
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; HRQMPWP; -.
DR OrthoDB; 757766at2759; -.
DR PhylomeDB; Q3ULB5; -.
DR TreeFam; TF105352; -.
DR Reactome; R-MMU-9013148; CDC42 GTPase cycle.
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; 1 hit in 75 CRISPR screens.
DR PRO; PR:Q3ULB5; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q3ULB5; protein.
DR Bgee; ENSMUSG00000074923; Expressed in embryonic brain and 119 other tissues.
DR Genevisible; Q3ULB5; MM.
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: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:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
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 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
