DAPK2_MOUSE
ID DAPK2_MOUSE Reviewed; 370 AA.
AC Q8VDF3; O88861; Q9QYM4;
DT 28-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2002, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Death-associated protein kinase 2;
DE Short=DAP kinase 2;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:Q9UIK4};
DE AltName: Full=DAP-kinase-related protein 1;
DE Short=DRP-1;
GN Name=Dapk2;
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 {ECO:0000312|EMBL:AAH22165.1};
RN [1] {ECO:0000312|EMBL:BAA88064.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [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 [3] {ECO:0000305}
RP NUCLEOTIDE SEQUENCE [MRNA] OF 68-370.
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 [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-299 AND SER-349, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-299 AND SER-349, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP ALTERNATIVE SPLICING (ISOFORM 2), AND TISSUE SPECIFICITY.
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 [7]
RP INTERACTION WITH 14-3-3 PROTEINS.
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 [8]
RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 11-370 IN COMPLEX WITH AMP AND
RP ATP, SUBUNIT, ACTIVITY REGULATION, AND AUTOINHIBITORY DOMAIN.
RX PubMed=21497605; DOI=10.1016/j.jmb.2011.03.065;
RA Patel A.K., Yadav R.P., Majava V., Kursula I., Kursula P.;
RT "Structure of the dimeric autoinhibited conformation of DAPK2, a pro-
RT apoptotic protein kinase.";
RL J. Mol. Biol. 409:369-383(2011).
RN [9]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=24906443; DOI=10.1186/1756-0500-7-345;
RA Guay J.A., Wojchowski D.M., Fang J., Oxburgh L.;
RT "Death associated protein kinase 2 is expressed in cortical interstitial
RT cells of the mouse kidney.";
RL BMC Res. Notes 7:345-345(2014).
RN [10]
RP FUNCTION.
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).
CC -!- FUNCTION: Calcium/calmodulin-dependent serine/threonine kinase involved
CC in multiple cellular signaling pathways that trigger cell survival,
CC apoptosis, and autophagy. Capable of regulating both type I apoptotic
CC and type II autophagic cell death signals. The former involves caspase
CC activation, chromatin and mitochondrial condensation while the latter
CC involves caspase-independent cell death in conjunction with
CC accumulation of mature autophagic vesicles, plasma membrane blebs, and
CC nuclear condensation without DNA degradation. Mediator of anoikis and a
CC suppressor of beta-catenin-dependent anchorage-independent growth of
CC malignant epithelial cells. May play a role in granulocytic maturation
CC (By similarity). Regulates granulocytes motility by controlling cell
CC spreading and polarization (PubMed:24163421).
CC {ECO:0000250|UniProtKB:Q9UIK4, ECO:0000269|PubMed:24163421}.
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:0000250|UniProtKB:Q9UIK4};
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:0000250|UniProtKB:Q9UIK4};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P53355};
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:21497605}.
CC -!- SUBUNIT: Homodimer in its autoinhibited state. Active as monomer.
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 {ECO:0000269|PubMed:21497605, ECO:0000269|PubMed:26047703}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cytoplasmic vesicle,
CC autophagosome lumen {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Alpha;
CC IsoId=Q8VDF3-1; Sequence=Displayed;
CC Name=2; Synonyms=Beta;
CC IsoId=Q8VDF3-2; Sequence=VSP_042058;
CC -!- TISSUE SPECIFICITY: Expressed in peritubular interstitial cells of the
CC renal cortex (PubMed:24906443). Isoform 1 is found in the adult brain
CC while isoform 2 is expressed in brains of embryos and young mice (at
CC protein level) (PubMed:21408167). {ECO:0000269|PubMed:21408167,
CC ECO:0000269|PubMed:24906443}.
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.
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:0000250|UniProtKB:Q9UIK4}.
CC -!- DISRUPTION PHENOTYPE: No visible phenotype.
CC {ECO:0000269|PubMed:24906443}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. DAP kinase subfamily. {ECO:0000305}.
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DR EMBL; AB018002; BAA88064.1; -; mRNA.
DR EMBL; BC022165; AAH22165.1; -; mRNA.
DR EMBL; AF052942; AAC35002.1; -; mRNA.
DR CCDS; CCDS23303.1; -. [Q8VDF3-1]
DR RefSeq; NP_034149.2; NM_010019.3. [Q8VDF3-1]
DR PDB; 2YA9; X-ray; 2.30 A; A/B=11-370.
DR PDB; 2YAA; X-ray; 2.30 A; A/B=11-370.
DR PDB; 2YAB; X-ray; 1.90 A; A/B=11-370.
DR PDBsum; 2YA9; -.
DR PDBsum; 2YAA; -.
DR PDBsum; 2YAB; -.
DR AlphaFoldDB; Q8VDF3; -.
DR SMR; Q8VDF3; -.
DR BioGRID; 199051; 1.
DR STRING; 10090.ENSMUSP00000034944; -.
DR iPTMnet; Q8VDF3; -.
DR PhosphoSitePlus; Q8VDF3; -.
DR EPD; Q8VDF3; -.
DR MaxQB; Q8VDF3; -.
DR PaxDb; Q8VDF3; -.
DR PRIDE; Q8VDF3; -.
DR ProteomicsDB; 279821; -. [Q8VDF3-1]
DR ProteomicsDB; 279822; -. [Q8VDF3-2]
DR Antibodypedia; 13340; 633 antibodies from 42 providers.
DR DNASU; 13143; -.
DR Ensembl; ENSMUST00000034944; ENSMUSP00000034944; ENSMUSG00000032380. [Q8VDF3-1]
DR GeneID; 13143; -.
DR KEGG; mmu:13143; -.
DR UCSC; uc009qen.2; mouse. [Q8VDF3-1]
DR CTD; 23604; -.
DR MGI; MGI:1341297; Dapk2.
DR VEuPathDB; HostDB:ENSMUSG00000032380; -.
DR eggNOG; KOG0032; Eukaryota.
DR GeneTree; ENSGT00940000153424; -.
DR HOGENOM; CLU_000288_63_0_1; -.
DR InParanoid; Q8VDF3; -.
DR OMA; NLRNCES; -.
DR OrthoDB; 813445at2759; -.
DR PhylomeDB; Q8VDF3; -.
DR TreeFam; TF314166; -.
DR BioGRID-ORCS; 13143; 1 hit in 76 CRISPR screens.
DR EvolutionaryTrace; Q8VDF3; -.
DR PRO; PR:Q8VDF3; -.
DR Proteomes; UP000000589; Chromosome 9.
DR RNAct; Q8VDF3; protein.
DR Bgee; ENSMUSG00000032380; Expressed in hindlimb stylopod muscle and 164 other tissues.
DR ExpressionAtlas; Q8VDF3; baseline and differential.
DR Genevisible; Q8VDF3; MM.
DR GO; GO:0034423; C:autophagosome lumen; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; ISS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; ISO:MGI.
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; ISO:MGI.
DR GO; GO:0035556; P:intracellular signal transduction; ISS:UniProtKB.
DR GO; GO:1990266; P:neutrophil migration; IMP:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IBA:GO_Central.
DR GO; GO:2000424; P:positive regulation of eosinophil chemotaxis; ISO:MGI.
DR GO; GO:0090023; P:positive regulation of neutrophil chemotaxis; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:2001242; P:regulation of intrinsic apoptotic signaling pathway; ISS: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_0000085913"
FT DOMAIN 23..285
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 287..354
FT /note="Calmodulin-binding"
FT /evidence="ECO:0000250"
FT REGION 292..301
FT /note="Autoinhibitory domain"
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 ECO:0000269|PubMed:21497605"
FT BINDING 52
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000269|PubMed:21497605"
FT MOD_RES 299
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 318
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:Q9UIK4"
FT MOD_RES 349
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355,
FT ECO:0007744|PubMed:21183079"
FT MOD_RES 369
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q9UIK4"
FT VAR_SEQ 286..370
FT /note="TPVDTQQAMVRRESVVNLENFKKQYVRRRWKLSFSIVSLCNHLTRSLMKKVH
FT LRTSEDLRNCESDTEENIARRKALHPRRRSSTS -> SKGEARAPEQWKAQPAQLKTKR
FT LREYTLKCHSSMPPNNTYVNFERFAHVVEDVARVDKGCRALAGAHDTLQDDVESLVSIY
FT NEKEAWYREENENARHNLSQLKYEYRKVESLKKLLREDIQATGASLGGVARKLDHLQAQ
FT FETLRQQLSADIQWMQELVGIFQLESENTDSHSLGFMFHRDPSESLSELLNRSHAEEVL
FT AGLSL (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_042058"
FT CONFLICT 89
FT /note="L -> R (in Ref. 3; AAC35002)"
FT /evidence="ECO:0000305"
FT CONFLICT 90
FT /note="H -> Q (in Ref. 1; BAA88064)"
FT /evidence="ECO:0000305"
FT CONFLICT 270
FT /note="T -> P (in Ref. 3; AAC35002)"
FT /evidence="ECO:0000305"
FT CONFLICT 341
FT /note="S -> I (in Ref. 3; AAC35002)"
FT /evidence="ECO:0000305"
FT HELIX 19..21
FT /evidence="ECO:0007829|PDB:2YAB"
FT STRAND 23..32
FT /evidence="ECO:0007829|PDB:2YAB"
FT STRAND 35..42
FT /evidence="ECO:0007829|PDB:2YAB"
FT TURN 43..45
FT /evidence="ECO:0007829|PDB:2YAB"
FT STRAND 48..56
FT /evidence="ECO:0007829|PDB:2YAB"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:2YA9"
FT STRAND 63..66
FT /evidence="ECO:0007829|PDB:2YAB"
FT HELIX 68..78
FT /evidence="ECO:0007829|PDB:2YAB"
FT STRAND 89..94
FT /evidence="ECO:0007829|PDB:2YAB"
FT STRAND 96..104
FT /evidence="ECO:0007829|PDB:2YAB"
FT HELIX 111..115
FT /evidence="ECO:0007829|PDB:2YAB"
FT HELIX 123..142
FT /evidence="ECO:0007829|PDB:2YAB"
FT HELIX 152..154
FT /evidence="ECO:0007829|PDB:2YAB"
FT STRAND 155..158
FT /evidence="ECO:0007829|PDB:2YAB"
FT STRAND 162..164
FT /evidence="ECO:0007829|PDB:2YAB"
FT STRAND 167..169
FT /evidence="ECO:0007829|PDB:2YAB"
FT HELIX 191..193
FT /evidence="ECO:0007829|PDB:2YAB"
FT HELIX 196..199
FT /evidence="ECO:0007829|PDB:2YAB"
FT HELIX 207..222
FT /evidence="ECO:0007829|PDB:2YAB"
FT HELIX 232..240
FT /evidence="ECO:0007829|PDB:2YAB"
FT HELIX 248..251
FT /evidence="ECO:0007829|PDB:2YAB"
FT HELIX 256..265
FT /evidence="ECO:0007829|PDB:2YAB"
FT TURN 270..272
FT /evidence="ECO:0007829|PDB:2YAB"
FT HELIX 276..280
FT /evidence="ECO:0007829|PDB:2YAB"
FT TURN 283..285
FT /evidence="ECO:0007829|PDB:2YAB"
FT HELIX 290..297
FT /evidence="ECO:0007829|PDB:2YAB"
FT HELIX 303..309
FT /evidence="ECO:0007829|PDB:2YAB"
SQ SEQUENCE 370 AA; 42778 MW; 7BF8577140B5F883 CRC64;
MVQASMRSPN METFKQQKVE DFYDIGEELG SGQFAIVKKC REKSTGLEYA AKFIKKRQSR
ASRRGVCREE IEREVSILRQ VLHPNIITLH DVYENRTDVV LILELVSGGE LFDFLAQKES
LSEEEATSFI KQILDGVNYL HTKKIAHFDL KPENIMLLDK NIPIPHIKLI DFGLAHEIED
GVEFKNIFGT PEFVAPEIVN YEPLGLEADM WSIGVITYIL LSGASPFLGD TKQETLANIT
AVSYDFDEEF FSQTSELAKD FIRKLLVKET RKRLTIQEAL RHPWITPVDT QQAMVRRESV
VNLENFKKQY VRRRWKLSFS IVSLCNHLTR SLMKKVHLRT SEDLRNCESD TEENIARRKA
LHPRRRSSTS
