DAPK2_HUMAN
ID DAPK2_HUMAN Reviewed; 370 AA.
AC Q9UIK4; E9JGM7; O75892; Q24JS1;
DT 28-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 191.
DE RecName: Full=Death-associated protein kinase 2;
DE Short=DAP kinase 2;
DE EC=2.7.11.1 {ECO:0000269|PubMed:10376525, ECO:0000269|PubMed:26047703};
DE AltName: Full=DAP-kinase-related protein 1;
DE Short=DRP-1;
GN Name=DAPK2;
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 {ECO:0000312|EMBL:BAA88063.1};
RN [1] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ACTIVITY REGULATION, TISSUE
RP SPECIFICITY, MUTAGENESIS OF LYS-52, AND CATALYTIC ACTIVITY.
RC TISSUE=Skeletal muscle {ECO:0000269|PubMed:10376525};
RX PubMed=10376525; DOI=10.1038/sj.onc.1202701;
RA Kawai T., Nomura F., Hoshino K., Copeland N.G., Gilbert D.J., Jenkins N.A.,
RA Akira S.;
RT "Death-associated protein kinase 2 is a new calcium/calmodulin-dependent
RT protein kinase that signals apoptosis through its catalytic activity.";
RL Oncogene 18:3471-3480(1999).
RN [2] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION,
RP HOMODIMERIZATION, AND MUTAGENESIS OF LYS-52.
RC TISSUE=Kidney {ECO:0000312|EMBL:AAC35001.1};
RX PubMed=10629061; DOI=10.1128/mcb.20.3.1044-1054.2000;
RA Inbal B., Shani G., Cohen O., Kissil J.L., Kimchi A.;
RT "Death-associated protein kinase-related protein 1, a novel
RT serine/threonine kinase involved in apoptosis.";
RL Mol. Cell. Biol. 20:1044-1054(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION (ISOFORM 2), TISSUE
RP SPECIFICITY, AND INTERACTION WITH ATF4 (ISOFORM 2).
RX PubMed=21408167; DOI=10.1371/journal.pone.0017344;
RA Shoval Y., Berissi H., Kimchi A., Pietrokovski S.;
RT "New modularity of DAP-kinases: alternative splicing of the DRP-1 gene
RT produces a ZIPk-like isoform.";
RL PLoS ONE 6:E17344-E17344(2011).
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 MRNA].
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 [6] {ECO:0000305}
RP FUNCTION, HOMODIMERIZATION, MUTAGENESIS OF LYS-52; SER-299; SER-318;
RP SER-320; SER-323 AND THR-329, AND PHOSPHORYLATION AT SER-318.
RX PubMed=11230133; DOI=10.1093/emboj/20.5.1099;
RA Shani G., Henis-Korenblit S., Jona G., Gileadi O., Eisenstein M., Ziv T.,
RA Admon A., Kimchi A.;
RT "Autophosphorylation restrains the apoptotic activity of DRP-1 kinase by
RT controlling dimerization and calmodulin binding.";
RL EMBO J. 20:1099-1113(2001).
RN [7]
RP REVIEW.
RX PubMed=12445458; DOI=10.1016/s1570-9639(02)00443-0;
RA Shohat G., Shani G., Eisenstein M., Kimchi A.;
RT "The DAP-kinase family of proteins: study of a novel group of calcium-
RT regulated death-promoting kinases.";
RL Biochim. Biophys. Acta 1600:45-50(2002).
RN [8]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=11980920; DOI=10.1083/jcb.200109094;
RA Inbal B., Bialik S., Sabanay I., Shani G., Kimchi A.;
RT "DAP kinase and DRP-1 mediate membrane blebbing and the formation of
RT autophagic vesicles during programmed cell death.";
RL J. Cell Biol. 157:455-468(2002).
RN [9]
RP REVIEW ON FUNCTION.
RX PubMed=16756490; DOI=10.1146/annurev.biochem.75.103004.142615;
RA Bialik S., Kimchi A.;
RT "The death-associated protein kinases: structure, function, and beyond.";
RL Annu. Rev. Biochem. 75:189-210(2006).
RN [10]
RP FUNCTION, INDUCTION, AND TISSUE SPECIFICITY.
RX PubMed=17347302; DOI=10.1189/jlb.0606400;
RA Rizzi M., Tschan M.P., Britschgi C., Britschgi A., Huegli B., Grob T.J.,
RA Leupin N., Mueller B.U., Simon H.U., Ziemiecki A., Torbett B.E., Fey M.F.,
RA Tobler A.;
RT "The death-associated protein kinase 2 is up-regulated during normal
RT myeloid differentiation and enhances neutrophil maturation in myeloid
RT leukemic cells.";
RL J. Leukoc. Biol. 81:1599-1608(2007).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-349, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [12]
RP FUNCTION.
RX PubMed=18957423; DOI=10.1074/jbc.m805612200;
RA Li H., Ray G., Yoo B.H., Erdogan M., Rosen K.V.;
RT "Down-regulation of death-associated protein kinase-2 is required for beta-
RT catenin-induced anoikis resistance of malignant epithelial cells.";
RL J. Biol. Chem. 284:2012-2022(2009).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-299 AND SER-349, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [14]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=24163421; DOI=10.1189/jlb.0813462;
RA Geering B., Stoeckle C., Rozman S., Oberson K., Benarafa C., Simon H.U.;
RT "DAPK2 positively regulates motility of neutrophils and eosinophils in
RT response to intermediary chemoattractants.";
RL J. Leukoc. Biol. 95:293-303(2014).
RN [15]
RP INTERACTION WITH 14-3-3 PROTEINS, MUTAGENESIS OF SER-367; SER-368; THR-369
RP AND SER-370, PHOSPHORYLATION AT THR-369, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=26047703; DOI=10.1016/j.bbrc.2015.05.105;
RA Yuasa K., Ota R., Matsuda S., Isshiki K., Inoue M., Tsuji A.;
RT "Suppression of death-associated protein kinase 2 by interaction with 14-3-
RT 3 proteins.";
RL Biochem. Biophys. Res. Commun. 464:70-75(2015).
RN [16]
RP VARIANTS [LARGE SCALE ANALYSIS] TRP-60 AND TRP-271.
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: Calcium/calmodulin-dependent serine/threonine kinase involved
CC in multiple cellular signaling pathways that trigger cell survival,
CC apoptosis, and autophagy. Regulates both type I apoptotic and type II
CC autophagic cell death signals, depending on the cellular setting. The
CC former is caspase-dependent, while the latter is caspase-independent
CC and is characterized by the accumulation of autophagic vesicles. Acts
CC as a mediator of anoikis and a suppressor of beta-catenin-dependent
CC anchorage-independent growth of malignant epithelial cells. May play a
CC role in granulocytic maturation (PubMed:17347302). Regulates
CC granulocytic motility by controlling cell spreading and polarization
CC (PubMed:24163421). {ECO:0000269|PubMed:17347302,
CC ECO:0000269|PubMed:24163421, ECO:0000269|PubMed:26047703}.
CC -!- FUNCTION: Isoform 2 is not regulated by calmodulin. It can
CC phosphorylate MYL9. It can induce membrane blebbing and autophagic cell
CC death.
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 Evidence={ECO:0000269|PubMed:10376525, ECO:0000269|PubMed:26047703};
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; Evidence={ECO:0000269|PubMed:10376525,
CC ECO:0000269|PubMed:26047703};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:10376525, ECO:0000269|PubMed:10629061,
CC ECO:0000269|PubMed:11230133};
CC -!- ACTIVITY REGULATION: Activated by Ca(2+)/calmodulin. Regulated by a
CC double locking mechanism, involving autophosphorylation at Ser-318,
CC calmodulin binding, and dimerization. In the inactive state, Ser-318 is
CC phosphorylated, and the kinase is dimeric. Activation involves:
CC dephosphorylation at Ser-318, release-of-autoinhibition mechanism where
CC calmodulin binding induces a conformational change that relieves the
CC steric block of the active site by the autoinhibitory domain, and
CC generation of the monomeric active form of the kinase.
CC {ECO:0000269|PubMed:10376525}.
CC -!- SUBUNIT: Homodimer in its autoinhibited state. Active as monomer (By
CC similarity). Isoform 2 but not isoform 1 can interact with ATF4.
CC Interacts with 14-3-3 proteins YWHAB, YWHAE, YWHAG, YWHAH, YWHAQ, YWHAZ
CC and SFN; the interaction requires DAPK2 phosphorylation at Thr-369 and
CC suppresses DAPK2 kinase activity and DAPK2-induced apoptosis
CC (PubMed:26047703). {ECO:0000250, ECO:0000269|PubMed:26047703}.
CC -!- INTERACTION:
CC Q9UIK4; Q7Z6B0-2: CCDC91; NbExp=3; IntAct=EBI-77154, EBI-12012082;
CC Q9UIK4; Q9UIK4: DAPK2; NbExp=4; IntAct=EBI-77154, EBI-77154;
CC Q9UIK4; Q8IZU0: FAM9B; NbExp=4; IntAct=EBI-77154, EBI-10175124;
CC Q9UIK4-2; P18848: ATF4; NbExp=2; IntAct=EBI-9693115, EBI-492498;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Cytoplasmic vesicle, autophagosome
CC lumen.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Alpha;
CC IsoId=Q9UIK4-1; Sequence=Displayed;
CC Name=2; Synonyms=Beta;
CC IsoId=Q9UIK4-2; Sequence=VSP_042057;
CC -!- TISSUE SPECIFICITY: Expressed in neutrophils and eosinophils
CC (PubMed:24163421). Isoform 2 is expressed in embryonic stem cells (at
CC protein level). Isoform 1 is ubiquitously expressed in all tissue types
CC examined with high levels in heart, lung and skeletal muscle.
CC {ECO:0000269|PubMed:10376525, ECO:0000269|PubMed:17347302,
CC ECO:0000269|PubMed:21408167, ECO:0000269|PubMed:24163421}.
CC -!- INDUCTION: Up-regulated during granulocytic maturation
CC (PubMed:17347302, PubMed:24163421). {ECO:0000269|PubMed:17347302,
CC ECO:0000269|PubMed:24163421}.
CC -!- DOMAIN: The autoinhibitory domain sterically blocks the substrate
CC peptide-binding site by making both hydrophobic and electrostatic
CC contacts with the kinase core. {ECO:0000250}.
CC -!- PTM: Autophosphorylation at Ser-318 inhibits its catalytic activity.
CC Dephosphorylated at Ser-318 in response to activated Fas and TNF-alpha
CC receptors. {ECO:0000269|PubMed:11230133}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. DAP kinase 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; AB018001; BAA88063.1; -; mRNA.
DR EMBL; AF052941; AAC35001.1; -; mRNA.
DR EMBL; GU056176; ADD83109.1; -; mRNA.
DR EMBL; AC015914; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC021541; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC114506; AAI14507.1; -; mRNA.
DR CCDS; CCDS10188.1; -. [Q9UIK4-1]
DR CCDS; CCDS86463.1; -. [Q9UIK4-2]
DR RefSeq; NP_055141.2; NM_014326.3. [Q9UIK4-1]
DR RefSeq; XP_011519718.1; XM_011521416.2.
DR PDB; 1WMK; X-ray; 3.60 A; A/B/C/D/E/F/G/H=11-330.
DR PDB; 1WRZ; X-ray; 2.00 A; B=312-330.
DR PDB; 1Z9X; X-ray; 3.93 A; A/B/C=11-330.
DR PDB; 1ZUZ; X-ray; 1.91 A; B=312-330.
DR PDB; 1ZWS; X-ray; 2.90 A; A/B/C/D/E/F/G/H=11-297.
DR PDB; 2A27; X-ray; 3.00 A; A/B/C/D/E/F/G/H=11-330.
DR PDB; 2A2A; X-ray; 1.47 A; A/B/C/D=11-330.
DR PDB; 2CKE; X-ray; 2.80 A; A/B/C/D=11-330.
DR PDB; 6PAW; X-ray; 2.95 A; A/B/E/F=12-330.
DR PDB; 7A6R; X-ray; 2.70 A; E/F/G/L=364-370.
DR PDB; 7A6Y; X-ray; 2.50 A; J/K/L/M=364-370.
DR PDBsum; 1WMK; -.
DR PDBsum; 1WRZ; -.
DR PDBsum; 1Z9X; -.
DR PDBsum; 1ZUZ; -.
DR PDBsum; 1ZWS; -.
DR PDBsum; 2A27; -.
DR PDBsum; 2A2A; -.
DR PDBsum; 2CKE; -.
DR PDBsum; 6PAW; -.
DR PDBsum; 7A6R; -.
DR PDBsum; 7A6Y; -.
DR AlphaFoldDB; Q9UIK4; -.
DR SMR; Q9UIK4; -.
DR BioGRID; 117137; 16.
DR IntAct; Q9UIK4; 10.
DR STRING; 9606.ENSP00000261891; -.
DR BindingDB; Q9UIK4; -.
DR ChEMBL; CHEMBL3123; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q9UIK4; -.
DR iPTMnet; Q9UIK4; -.
DR PhosphoSitePlus; Q9UIK4; -.
DR BioMuta; DAPK2; -.
DR DMDM; 38605084; -.
DR EPD; Q9UIK4; -.
DR jPOST; Q9UIK4; -.
DR MassIVE; Q9UIK4; -.
DR MaxQB; Q9UIK4; -.
DR PaxDb; Q9UIK4; -.
DR PeptideAtlas; Q9UIK4; -.
DR PRIDE; Q9UIK4; -.
DR ProteomicsDB; 19027; -.
DR ProteomicsDB; 84537; -. [Q9UIK4-1]
DR ProteomicsDB; 84538; -. [Q9UIK4-2]
DR Antibodypedia; 13340; 633 antibodies from 42 providers.
DR DNASU; 23604; -.
DR Ensembl; ENST00000261891.7; ENSP00000261891.3; ENSG00000035664.11. [Q9UIK4-1]
DR Ensembl; ENST00000457488.5; ENSP00000408277.1; ENSG00000035664.11. [Q9UIK4-1]
DR Ensembl; ENST00000558069.5; ENSP00000453235.1; ENSG00000035664.11. [Q9UIK4-2]
DR Ensembl; ENST00000612884.4; ENSP00000484390.1; ENSG00000035664.11. [Q9UIK4-2]
DR GeneID; 23604; -.
DR KEGG; hsa:23604; -.
DR MANE-Select; ENST00000457488.6; ENSP00000408277.1; NM_014326.5; NP_055141.2.
DR UCSC; uc002amr.4; human. [Q9UIK4-1]
DR CTD; 23604; -.
DR DisGeNET; 23604; -.
DR GeneCards; DAPK2; -.
DR HGNC; HGNC:2675; DAPK2.
DR HPA; ENSG00000035664; Tissue enhanced (skeletal muscle, thyroid gland).
DR MIM; 616567; gene.
DR neXtProt; NX_Q9UIK4; -.
DR OpenTargets; ENSG00000035664; -.
DR PharmGKB; PA27143; -.
DR VEuPathDB; HostDB:ENSG00000035664; -.
DR eggNOG; KOG0032; Eukaryota.
DR GeneTree; ENSGT00940000153424; -.
DR HOGENOM; CLU_000288_63_0_1; -.
DR InParanoid; Q9UIK4; -.
DR OMA; NLRNCES; -.
DR OrthoDB; 813445at2759; -.
DR PhylomeDB; Q9UIK4; -.
DR TreeFam; TF314166; -.
DR PathwayCommons; Q9UIK4; -.
DR Reactome; R-HSA-418889; Caspase activation via Dependence Receptors in the absence of ligand.
DR SignaLink; Q9UIK4; -.
DR SIGNOR; Q9UIK4; -.
DR BioGRID-ORCS; 23604; 10 hits in 1110 CRISPR screens.
DR ChiTaRS; DAPK2; human.
DR EvolutionaryTrace; Q9UIK4; -.
DR GeneWiki; DAPK2; -.
DR GenomeRNAi; 23604; -.
DR Pharos; Q9UIK4; Tchem.
DR PRO; PR:Q9UIK4; -.
DR Proteomes; UP000005640; Chromosome 15.
DR RNAct; Q9UIK4; protein.
DR Bgee; ENSG00000035664; Expressed in right lobe of thyroid gland and 178 other tissues.
DR ExpressionAtlas; Q9UIK4; baseline and differential.
DR Genevisible; Q9UIK4; HS.
DR GO; GO:0034423; C:autophagosome lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
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:0043276; P:anoikis; IMP:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; TAS:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:2000424; P:positive regulation of eosinophil chemotaxis; IMP:UniProtKB.
DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; IMP:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; TAS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IDA:UniProtKB.
DR GO; GO:0042981; P:regulation of apoptotic process; TAS:UniProtKB.
DR GO; GO:0010506; P:regulation of autophagy; TAS:UniProtKB.
DR GO; GO:2001242; P:regulation of intrinsic apoptotic signaling pathway; IMP:UniProtKB.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 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 3D-structure; Alternative splicing; Apoptosis; ATP-binding;
KW Calmodulin-binding; Cytoplasm; Cytoplasmic vesicle; Kinase;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..370
FT /note="Death-associated protein kinase 2"
FT /id="PRO_0000085912"
FT DOMAIN 23..285
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 277..344
FT /note="Calmodulin-binding"
FT REGION 292..301
FT /note="Autoinhibitory domain"
FT /evidence="ECO:0000250"
FT REGION 348..370
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 149
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 29..37
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 52
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:10376525, ECO:0000269|PubMed:10629061"
FT MOD_RES 299
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 318
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:11230133"
FT MOD_RES 349
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 369
FT /note="Phosphothreonine; by PKB/AKT1"
FT /evidence="ECO:0000269|PubMed:26047703"
FT VAR_SEQ 287..370
FT /note="PVDNQQAMVRRESVVNLENFRKQYVRRRWKLSFSIVSLCNHLTRSLMKKVHL
FT RPDEDLRNCESDTEEDIARRKALHPRRRSSTS -> SKGEGRAPEQRKTEPTQLKTKHL
FT REYTLKCHSSMPPNNSYVNFERFACVVEDVARVDLGCRALVEAHDTIQDDVEALVSIFN
FT EKEAWYREENESARHDLSQLRYEFRKVESLKKLLREDIQATGCSLGSMARKLDHLQAQF
FT EILRQELSADLQWIQELVGSFQLESGSSEGLGSTFYQDTSESLSELLSRSCTEEFLAGW
FT KL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:21408167"
FT /id="VSP_042057"
FT VARIANT 60
FT /note="R -> W (in dbSNP:rs56047843)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040436"
FT VARIANT 271
FT /note="R -> W (in dbSNP:rs34270163)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040437"
FT MUTAGEN 52
FT /note="K->A: Loss of activity, apoptotic function and of
FT autophosphorylation."
FT /evidence="ECO:0000269|PubMed:10376525,
FT ECO:0000269|PubMed:10629061, ECO:0000269|PubMed:11230133"
FT MUTAGEN 299..330
FT /note="Missing: Loss of ca(2+)-calmodulin binding, increase
FT in activity, loss of autophosphorylation."
FT MUTAGEN 299
FT /note="S->A: No effect on Ca(2+)-calmodulin independent
FT phosphorylation or apoptotic activity."
FT /evidence="ECO:0000269|PubMed:11230133"
FT MUTAGEN 318
FT /note="S->A: Loss of Ca(2+)-calmodulin independent
FT phosphorylation, increase in apoptotic activity."
FT /evidence="ECO:0000269|PubMed:11230133"
FT MUTAGEN 318
FT /note="S->D: Abolishes apoptotic activity."
FT /evidence="ECO:0000269|PubMed:11230133"
FT MUTAGEN 320
FT /note="S->A: No effect on Ca(2+)-calmodulin independent
FT phosphorylation or apoptotic activity."
FT /evidence="ECO:0000269|PubMed:11230133"
FT MUTAGEN 323
FT /note="S->A: No effect on Ca(2+)-calmodulin independent
FT phosphorylation or apoptotic activity."
FT /evidence="ECO:0000269|PubMed:11230133"
FT MUTAGEN 329
FT /note="T->A: No effect on Ca(2+)-calmodulin independent
FT phosphorylation or apoptotic activity."
FT /evidence="ECO:0000269|PubMed:11230133"
FT MUTAGEN 367
FT /note="S->A: No effect on interaction with YWHAE."
FT /evidence="ECO:0000269|PubMed:26047703"
FT MUTAGEN 368
FT /note="S->A: No effect on interaction with YWHAE."
FT /evidence="ECO:0000269|PubMed:26047703"
FT MUTAGEN 369
FT /note="T->A: Interaction with YWHAE is reduced."
FT /evidence="ECO:0000269|PubMed:26047703"
FT MUTAGEN 370
FT /note="S->A: Interaction with YWHAE is increased."
FT /evidence="ECO:0000269|PubMed:26047703"
FT CONFLICT 241
FT /note="A -> S (in Ref. 2; AAC35001)"
FT /evidence="ECO:0000305"
FT CONFLICT 253
FT /note="Q -> H (in Ref. 2; AAC35001)"
FT /evidence="ECO:0000305"
FT HELIX 19..22
FT /evidence="ECO:0007829|PDB:2A2A"
FT STRAND 23..31
FT /evidence="ECO:0007829|PDB:2A2A"
FT STRAND 33..42
FT /evidence="ECO:0007829|PDB:2A2A"
FT TURN 43..45
FT /evidence="ECO:0007829|PDB:2A2A"
FT STRAND 48..56
FT /evidence="ECO:0007829|PDB:2A2A"
FT STRAND 58..61
FT /evidence="ECO:0007829|PDB:2A2A"
FT STRAND 63..66
FT /evidence="ECO:0007829|PDB:2A2A"
FT HELIX 68..80
FT /evidence="ECO:0007829|PDB:2A2A"
FT STRAND 89..94
FT /evidence="ECO:0007829|PDB:2A2A"
FT STRAND 96..103
FT /evidence="ECO:0007829|PDB:2A2A"
FT HELIX 111..116
FT /evidence="ECO:0007829|PDB:2A2A"
FT HELIX 123..142
FT /evidence="ECO:0007829|PDB:2A2A"
FT STRAND 144..146
FT /evidence="ECO:0007829|PDB:1ZWS"
FT HELIX 152..154
FT /evidence="ECO:0007829|PDB:2A2A"
FT STRAND 155..158
FT /evidence="ECO:0007829|PDB:2A2A"
FT STRAND 162..164
FT /evidence="ECO:0007829|PDB:2A2A"
FT STRAND 167..169
FT /evidence="ECO:0007829|PDB:2A2A"
FT HELIX 191..193
FT /evidence="ECO:0007829|PDB:2A2A"
FT HELIX 196..199
FT /evidence="ECO:0007829|PDB:2A2A"
FT HELIX 207..222
FT /evidence="ECO:0007829|PDB:2A2A"
FT HELIX 232..240
FT /evidence="ECO:0007829|PDB:2A2A"
FT HELIX 248..251
FT /evidence="ECO:0007829|PDB:2A2A"
FT HELIX 256..263
FT /evidence="ECO:0007829|PDB:2A2A"
FT TURN 270..272
FT /evidence="ECO:0007829|PDB:2A2A"
FT HELIX 276..281
FT /evidence="ECO:0007829|PDB:2A2A"
FT TURN 283..285
FT /evidence="ECO:0007829|PDB:2A2A"
FT HELIX 290..298
FT /evidence="ECO:0007829|PDB:2A2A"
FT HELIX 303..312
FT /evidence="ECO:0007829|PDB:2A2A"
FT HELIX 314..328
FT /evidence="ECO:0007829|PDB:1ZUZ"
FT REGION Q9UIK4-2:434..451
FT /note="Leucine-zipper"
FT /evidence="ECO:0000305"
SQ SEQUENCE 370 AA; 42898 MW; 035E914BBCD881A2 CRC64;
MFQASMRSPN MEPFKQQKVE DFYDIGEELG SGQFAIVKKC REKSTGLEYA AKFIKKRQSR
ASRRGVSREE IEREVSILRQ VLHHNVITLH DVYENRTDVV LILELVSGGE LFDFLAQKES
LSEEEATSFI KQILDGVNYL HTKKIAHFDL KPENIMLLDK NIPIPHIKLI DFGLAHEIED
GVEFKNIFGT PEFVAPEIVN YEPLGLEADM WSIGVITYIL LSGASPFLGD TKQETLANIT
AVSYDFDEEF FSQTSELAKD FIRKLLVKET RKRLTIQEAL RHPWITPVDN QQAMVRRESV
VNLENFRKQY VRRRWKLSFS IVSLCNHLTR SLMKKVHLRP DEDLRNCESD TEEDIARRKA
LHPRRRSSTS
