ID Q6DG42_DANRE Unreviewed; 517 AA.
AC Q6DG42; A0A0R4IQG0; A0A8N7XJE5; B2GRT8;
DT 16-AUG-2004, integrated into UniProtKB/TrEMBL.
DT 16-AUG-2004, sequence version 1.
DT 27-MAR-2024, entry version 165.
DE RecName: Full=non-specific serine/threonine protein kinase {ECO:0000256|ARBA:ARBA00012513};
DE EC=2.7.11.1 {ECO:0000256|ARBA:ARBA00012513};
GN Name=pak2a {ECO:0000313|EMBL:AAI65251.1,
GN ECO:0000313|Ensembl:ENSDARP00000089188,
GN ECO:0000313|RefSeq:NP_001002717.1, ECO:0000313|RefSeq:XP_005171319.1,
GN ECO:0000313|RefSeq:XP_005171320.1,
GN ECO:0000313|ZFIN:ZDB-GENE-021011-2};
GN Synonyms=cb422 {ECO:0000313|RefSeq:NP_001002717.1,
GN ECO:0000313|RefSeq:XP_005171319.1}, kinase
GN {ECO:0000313|RefSeq:XP_005171319.1,
GN ECO:0000313|RefSeq:XP_005171320.1}, pak2
GN {ECO:0000313|RefSeq:NP_001002717.1,
GN ECO:0000313|RefSeq:XP_005171320.1}, si:dz198m22.1
GN {ECO:0000313|RefSeq:NP_001002717.1, ECO:0000313|RefSeq:XP_005171319.1,
GN ECO:0000313|RefSeq:XP_005171320.1}, wu:fb71h01
GN {ECO:0000313|RefSeq:NP_001002717.1, ECO:0000313|RefSeq:XP_005171319.1,
GN ECO:0000313|RefSeq:XP_005171320.1}, zgc:91798
GN {ECO:0000313|RefSeq:NP_001002717.1, ECO:0000313|RefSeq:XP_005171319.1,
GN ECO:0000313|RefSeq:XP_005171320.1};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955 {ECO:0000313|EMBL:AAI65251.1};
RN [1] {ECO:0000313|RefSeq:NP_001002717.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=16322560; DOI=10.1101/gad.1366405;
RA Chen J., Ruan H., Ng S.M., Gao C., Soo H.M., Wu W., Zhang Z., Wen Z.,
RA Lane D.P., Peng J.;
RT "Loss of function of def selectively up-regulates Delta113p53 expression to
RT arrest expansion growth of digestive organs in zebrafish.";
RL Genes Dev. 19:2900-2911(2005).
RN [2] {ECO:0000313|RefSeq:NP_001002717.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=15630097; DOI=10.1073/pnas.0406252102;
RA Berghmans S., Murphey R.D., Wienholds E., Neuberg D., Kutok J.L.,
RA Fletcher C.D., Morris J.P., Liu T.X., Schulte-Merker S., Kanki J.P.,
RA Plasterk R., Zon L.I., Look A.T.;
RT "tp53 mutant zebrafish develop malignant peripheral nerve sheath tumors.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:407-412(2005).
RN [3] {ECO:0000313|RefSeq:NP_001002717.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=17573532; DOI=10.1073/pnas.0700825104;
RA Liu J., Fraser S.D., Faloon P.W., Rollins E.L., Vom Berg J.,
RA Starovic-Subota O., Laliberte A.L., Chen J.N., Serluca F.C., Childs S.J.;
RT "A betaPix Pak2a signaling pathway regulates cerebral vascular stability in
RT zebrafish.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:13990-13995(2007).
RN [4] {ECO:0000313|RefSeq:NP_001002717.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=17715297;
RA Buchner D.A., Su F., Yamaoka J.S., Kamei M., Shavit J.A., Barthel L.K.,
RA McGee B., Amigo J.D., Kim S., Hanosh A.W., Jagadeeswaran P., Goldman D.,
RA Lawson N.D., Raymond P.A., Weinstein B.M., Ginsburg D., Lyons S.E.;
RT "pak2a mutations cause cerebral hemorrhage in redhead zebrafish.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:13996-14001(2007).
RN [5] {ECO:0000313|RefSeq:NP_001002717.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=19093037;
RA Gore A.V., Lampugnani M.G., Dye L., Dejana E., Weinstein B.M.;
RT "Combinatorial interaction between CCM pathway genes precipitates
RT hemorrhagic stroke.";
RL Dis. Model. Mech. 1:275-281(2008).
RN [6] {ECO:0000313|EMBL:AAI65251.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=PCR rescue {ECO:0000313|EMBL:AAI65251.1}, and Whole
RC {ECO:0000313|EMBL:AAH76511.1};
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (APR-2008) to the EMBL/GenBank/DDBJ databases.
RN [7] {ECO:0000313|Ensembl:ENSDARP00000089188}
RP IDENTIFICATION.
RC STRAIN=Tuebingen {ECO:0000313|Ensembl:ENSDARP00000089188};
RG Ensembl;
RL Submitted (FEB-2012) to UniProtKB.
RN [8] {ECO:0000313|Ensembl:ENSDARP00000089188, ECO:0000313|Proteomes:UP000000437}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen {ECO:0000313|Ensembl:ENSDARP00000089188};
RX PubMed=23594743; DOI=10.1038/nature12111;
RG Genome Reference Consortium Zebrafish;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Eliott D.,
RA Threadgold G., Harden G., Ware D., Begum S., Mortimore B., Mortimer B.,
RA Kerry G., Heath P., Phillimore B., Tracey A., Corby N., Dunn M.,
RA Johnson C., Wood J., Clark S., Pelan S., Griffiths G., Smith M.,
RA Glithero R., Howden P., Barker N., Lloyd C., Stevens C., Harley J.,
RA Holt K., Panagiotidis G., Lovell J., Beasley H., Henderson C., Gordon D.,
RA Auger K., Wright D., Collins J., Raisen C., Dyer L., Leung K.,
RA Robertson L., Ambridge K., Leongamornlert D., McGuire S., Gilderthorp R.,
RA Griffiths C., Manthravadi D., Nichol S., Barker G., Whitehead S., Kay M.,
RA Brown J., Murnane C., Gray E., Humphries M., Sycamore N., Barker D.,
RA Saunders D., Wallis J., Babbage A., Hammond S., Mashreghi-Mohammadi M.,
RA Barr L., Martin S., Wray P., Ellington A., Matthews N., Ellwood M.,
RA Woodmansey R., Clark G., Cooper J., Cooper J., Tromans A., Grafham D.,
RA Skuce C., Pandian R., Andrews R., Harrison E., Kimberley A., Garnett J.,
RA Fosker N., Hall R., Garner P., Kelly D., Bird C., Palmer S., Gehring I.,
RA Berger A., Dooley C.M., Ersan-Urun Z., Eser C., Geiger H., Geisler M.,
RA Karotki L., Kirn A., Konantz J., Konantz M., Oberlander M.,
RA Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G., Osoegawa K., Zhu B.,
RA Rapp A., Widaa S., Langford C., Yang F., Schuster S.C., Carter N.P.,
RA Harrow J., Ning Z., Herrero J., Searle S.M., Enright A., Geisler R.,
RA Plasterk R.H., Lee C., Westerfield M., de Jong P.J., Zon L.I.,
RA Postlethwait J.H., Nusslein-Volhard C., Hubbard T.J., Roest Crollius H.,
RA Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [9] {ECO:0000313|RefSeq:NP_001002717.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=25526262;
RA Ellis L.D., Soo E.C., Achenbach J.C., Morash M.G., Soanes K.H.;
RT "Use of the zebrafish larvae as a model to study cigarette smoke condensate
RT toxicity.";
RL PLoS ONE 9:e115305-e115305(2014).
RN [10] {ECO:0000313|RefSeq:NP_001002717.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=25725065;
RA Choe C.P., Crump J.G.;
RT "Eph-Pak2a signaling regulates branching of the pharyngeal endoderm by
RT inhibiting late-stage epithelial dynamics.";
RL Development 142:1089-1094(2015).
RN [11] {ECO:0000313|RefSeq:NP_001002717.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=26469318;
RA Elkon R., Milon B., Morrison L., Shah M., Vijayakumar S., Racherla M.,
RA Leitch C.C., Silipino L., Hadi S., Weiss-Gayet M., Barras E., Schmid C.D.,
RA Ait-Lounis A., Barnes A., Song Y., Eisenman D.J., Eliyahu E.,
RA Frolenkov G.I., Strome S.E., Durand B., Zaghloul N.A., Jones S.M.,
RA Reith W., Hertzano R.;
RT "RFX transcription factors are essential for hearing in mice.";
RL Nat. Commun. 6:8549-8549(2015).
RN [12] {ECO:0000313|Ensembl:ENSDARP00000137659}
RP IDENTIFICATION.
RC STRAIN=Tuebingen {ECO:0000313|Ensembl:ENSDARP00000137659};
RG Ensembl;
RL Submitted (NOV-2015) to UniProtKB.
RN [13] {ECO:0000313|RefSeq:NP_001002717.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=27581547;
RA Jagadeeshan S., Sagayaraj R.V., Paneerselvan N., Ghouse S.S., Malathi R.;
RT "Toxicity and anti-angiogenicity evaluation of Pak1 inhibitor IPA-3 using
RT zebrafish embryo model.";
RL Cell Biol. Toxicol. 33:41-56(2017).
RN [14] {ECO:0000313|RefSeq:NP_001002717.1}
RP NUCLEOTIDE SEQUENCE.
RX PubMed=28252024;
RA Bayes A., Collins M.O., Reig-Viader R., Gou G., Goulding D., Izquierdo A.,
RA Choudhary J.S., Emes R.D., Grant S.G.;
RT "Evolution of complexity in the zebrafish synapse proteome.";
RL Nat. Commun. 8:14613-14613(2017).
RN [15] {ECO:0000313|RefSeq:NP_001002717.1, ECO:0000313|RefSeq:XP_005171319.1}
RP IDENTIFICATION.
RC STRAIN=Tuebingen {ECO:0000313|RefSeq:XP_005171319.1,
RC ECO:0000313|RefSeq:XP_005171320.1};
RG RefSeq;
RL Submitted (NOV-2023) to UniProtKB.
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DR EMBL; BX901889; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC076511; AAH76511.1; -; mRNA.
DR EMBL; BC165251; AAI65251.1; -; mRNA.
DR RefSeq; NP_001002717.1; NM_001002717.1.
DR RefSeq; XP_005171319.1; XM_005171262.4.
DR RefSeq; XP_005171320.1; XM_005171263.4.
DR PaxDb; 7955-ENSDARP00000089188; -.
DR Ensembl; ENSDART00000098417.3; ENSDARP00000089188.2; ENSDARG00000068177.7.
DR Ensembl; ENSDART00000159541.2; ENSDARP00000137659.2; ENSDARG00000068177.7.
DR Ensembl; ENSDART00000177428.2; ENSDARP00000144014.1; ENSDARG00000068177.7.
DR GeneID; 266749; -.
DR KEGG; dre:266749; -.
DR AGR; ZFIN:ZDB-GENE-021011-2; -.
DR CTD; 266749; -.
DR ZFIN; ZDB-GENE-021011-2; pak2a.
DR eggNOG; KOG0578; Eukaryota.
DR HOGENOM; CLU_000288_26_6_1; -.
DR OrthoDB; 460351at2759; -.
DR TreeFam; TF105351; -.
DR Proteomes; UP000000437; Chromosome 2.
DR Bgee; ENSDARG00000068177; Expressed in granulocyte and 47 other cell types or tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-UniRule.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0001568; P:blood vessel development; IMP:ZFIN.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0050770; P:regulation of axonogenesis; IBA:GO_Central.
DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
DR CDD; cd01093; CRIB_PAK_like; 1.
DR CDD; cd06655; STKc_PAK2; 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; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR035064; STK_PAK2.
DR PANTHER; PTHR48015; SERINE/THREONINE-PROTEIN KINASE TAO; 1.
DR PANTHER; PTHR48015:SF22; SERINE_THREONINE-PROTEIN KINASE PAK 2; 1.
DR Pfam; PF00786; PBD; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00285; PBD; 1.
DR SMART; SM00220; S_TKc; 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 PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 1: Evidence at protein level;
KW ATP-binding {ECO:0000256|ARBA:ARBA00022840, ECO:0000256|PROSITE-
KW ProRule:PRU10141};
KW Kinase {ECO:0000313|EMBL:AAH76511.1, ECO:0000313|RefSeq:NP_001002717.1};
KW Nucleotide-binding {ECO:0000256|ARBA:ARBA00022741, ECO:0000256|PROSITE-
KW ProRule:PRU10141};
KW Proteomics identification {ECO:0007829|PeptideAtlas:Q6DG42};
KW Reference proteome {ECO:0000313|Proteomes:UP000000437};
KW Transferase {ECO:0000313|EMBL:AAH76511.1,
KW ECO:0000313|RefSeq:NP_001002717.1}.
FT DOMAIN 75..88
FT /note="CRIB"
FT /evidence="ECO:0000259|PROSITE:PS50108"
FT DOMAIN 242..493
FT /note="Protein kinase"
FT /evidence="ECO:0000259|PROSITE:PS50011"
FT REGION 1..86
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 142..179
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 198..221
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 17..39
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 41..79
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 207..221
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 271
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000256|PROSITE-ProRule:PRU10141"
SQ SEQUENCE 517 AA; 57308 MW; 8D37FEACCE28A07F CRC64;
MSDNGELEDK PPAPPVRMSS TFSTGIKDSM STNPSSKPLP SVPEEKRDKP RNKIISIFSA
EKGRKKDKDK ERPEISNPSD FEHTIHVGFD SVTGEFTGMP EQWARLLQTS NITKSEQKKN
PQAVLDVLKF YDSTGNSRQK YLSFTDKDAP QAKKGSEQSP VKDPDDDDED APPPVVAPRP
QHTISVYTRS VIDPIPAPAA IADTDGSKAA DKQKKGKGKM TDEEIMEKLR TIVSIGDPKK
KYTRYEKIGQ GASGTVYTAI DVATGQEVAI KQINLQKQPK KELIINEILV MKELKNPNIV
NFLDSFLVGD ELFVVMEYLA GGSLTDVVTE TCMDEAQIAA VCRECLQALE FLHANQVIHR
DIKSDNVLLG MDGSVKLTDF GFCAQITPEQ SKRSTMVGTP YWMAPEVVTR KAYGPKVDIW
SLGIMAIEMV EGEPPYLNEN PLRALYLIAT NGTPELQNPE KLSPIFRDFL NRCLEMDVEK
RGGGKELLQH PFLKLAKPLS SLTPLILAAK EAMKSNR
//