DAPK1_HUMAN
ID DAPK1_HUMAN Reviewed; 1430 AA.
AC P53355; B7ZLD2; B7ZLE7; Q14CQ7; Q1W5W0; Q68CP8; Q6ZRZ3; Q9BTL8;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 11-JAN-2011, sequence version 6.
DT 03-AUG-2022, entry version 225.
DE RecName: Full=Death-associated protein kinase 1;
DE Short=DAP kinase 1;
DE EC=2.7.11.1;
GN Name=DAPK1; Synonyms=DAPK;
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INDUCTION, MUTAGENESIS OF
RP LYS-42, AND VARIANT ASN-1346.
RX PubMed=7828849; DOI=10.1101/gad.9.1.15;
RA Deiss L.P., Feinstein E., Berissi H., Cohen O., Kimchi A.;
RT "Identification of a novel serine/threonine kinase and a novel 15-kD
RT protein as potential mediators of the gamma interferon-induced cell
RT death.";
RL Genes Dev. 9:15-30(1995).
RN [2]
RP SEQUENCE REVISION TO 164-171.
RA Feinstein E.;
RL Submitted (APR-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ASN-1346.
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-591; MET-622; ASN-1346
RP AND VAL-1405.
RG NIEHS SNPs program;
RL Submitted (MAR-2006) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT ASN-1346.
RX PubMed=15164053; DOI=10.1038/nature02465;
RA Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L.,
RA Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R.,
RA Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S.,
RA Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K.,
RA Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C.,
RA Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E.,
RA Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M.,
RA Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J.,
RA Frankish A., Frankland J.A., French L., Fricker D.G., Garner P.,
RA Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S.,
RA Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E.,
RA Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D.,
RA Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E.,
RA Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K.,
RA Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S.,
RA Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E.,
RA McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V.,
RA Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S.,
RA Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K.,
RA Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J.,
RA Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M.,
RA West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L.,
RA Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M.,
RA Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J.,
RA Dunham I.;
RT "DNA sequence and analysis of human chromosome 9.";
RL Nature 429:369-374(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 4).
RC TISSUE=Cerebellum;
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-363.
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP FUNCTION, AND SUBCELLULAR LOCATION.
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 [11]
RP FUNCTION, ACTIVITY REGULATION, MUTAGENESIS OF LYS-42; SER-308 AND SER-313,
RP AND PHOSPHORYLATION AT SER-308.
RX PubMed=11579085; DOI=10.1074/jbc.m105133200;
RA Shohat G., Spivak-Kroizman T., Cohen O., Bialik S., Shani G., Berissi H.,
RA Eisenstein M., Kimchi A.;
RT "The pro-apoptotic function of death-associated protein kinase is
RT controlled by a unique inhibitory autophosphorylation-based mechanism.";
RL J. Biol. Chem. 276:47460-47467(2001).
RN [12]
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 [13]
RP FUNCTION IN PHOSPHORYLATION OF STX1A, AND INTERACTION WITH STX1A.
RX PubMed=12730201; DOI=10.1074/jbc.m300492200;
RA Tian J.H., Das S., Sheng Z.H.;
RT "Ca2+-dependent phosphorylation of syntaxin-1A by the death-associated
RT protein (DAP) kinase regulates its interaction with Munc18.";
RL J. Biol. Chem. 278:26265-26274(2003).
RN [14]
RP FUNCTION IN PHOSPHORYLATION OF DAPK3, AND INTERACTION WITH DAPK3.
RX PubMed=15367680; DOI=10.1128/mcb.24.19.8611-8626.2004;
RA Shani G., Marash L., Gozuacik D., Bialik S., Teitelbaum L., Shohat G.,
RA Kimchi A.;
RT "Death-associated protein kinase phosphorylates ZIP kinase, forming a
RT unique kinase hierarchy to activate its cell death functions.";
RL Mol. Cell. Biol. 24:8611-8626(2004).
RN [15]
RP INTERACTION WITH PDCD6.
RX PubMed=16132846; DOI=10.1007/s10529-005-7869-x;
RA Lee J.H., Rho S.B., Chun T.;
RT "Programmed cell death 6 (PDCD6) protein interacts with death-associated
RT protein kinase 1 (DAPk1): additive effect on apoptosis via caspase-3
RT dependent pathway.";
RL Biotechnol. Lett. 27:1011-1015(2005).
RN [16]
RP PHOSPHORYLATION AT SER-289.
RX PubMed=16213824; DOI=10.1016/j.cub.2005.08.050;
RA Anjum R., Roux P.P., Ballif B.A., Gygi S.P., Blenis J.;
RT "The tumor suppressor DAP kinase is a target of RSK-mediated survival
RT signaling.";
RL Curr. Biol. 15:1762-1767(2005).
RN [17]
RP PHOSPHORYLATION AT SER-734, AND INTERACTION WITH MAPK1 AND MAPK3.
RX PubMed=15616583; DOI=10.1038/sj.emboj.7600510;
RA Chen C.H., Wang W.J., Kuo J.C., Tsai H.C., Lin J.R., Chang Z.F., Chen R.H.;
RT "Bidirectional signals transduced by DAPK-ERK interaction promote the
RT apoptotic effect of DAPK.";
RL EMBO J. 24:294-304(2005).
RN [18]
RP PHOSPHORYLATION AT SER-308, ACTIVITY REGULATION, AND INTERACTION WITH
RP UNC5B.
RX PubMed=15729359; DOI=10.1038/sj.emboj.7600584;
RA Llambi F., Lourenco F.C., Gozuacik D., Guix C., Pays L., Del Rio G.,
RA Kimchi A., Mehlen P.;
RT "The dependence receptor UNC5H2 mediates apoptosis through DAP-kinase.";
RL EMBO J. 24:1192-1201(2005).
RN [19]
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 [20]
RP ALTERNATIVE SPLICING (ISOFORM 3), PHOSPHORYLATION AT SER-308,
RP DEPHOSPHORYLATION, AND ACTIVITY REGULATION.
RX PubMed=17056602; DOI=10.1074/jbc.m605097200;
RA Jin Y., Blue E.K., Gallagher P.J.;
RT "Control of death-associated protein kinase (DAPK) activity by
RT phosphorylation and proteasomal degradation.";
RL J. Biol. Chem. 281:39033-39040(2006).
RN [21]
RP FUNCTION IN PHOSPHORYLATION OF PRKD1, AND INTERACTION WITH PRKD1.
RX PubMed=17703233; DOI=10.1038/sj.cdd.4402212;
RA Eisenberg-Lerner A., Kimchi A.;
RT "DAP kinase regulates JNK signaling by binding and activating protein
RT kinase D under oxidative stress.";
RL Cell Death Differ. 14:1908-1915(2007).
RN [22]
RP FUNCTION IN PHOSPHORYLATION OF TPM1.
RX PubMed=17895359; DOI=10.1242/jcs.003251;
RA Houle F., Poirier A., Dumaresq J., Huot J.;
RT "DAP kinase mediates the phosphorylation of tropomyosin-1 downstream of the
RT ERK pathway, which regulates the formation of stress fibers in response to
RT oxidative stress.";
RL J. Cell Sci. 120:3666-3677(2007).
RN [23]
RP ALTERNATIVE SPLICING (ISOFORM 2), PROTEOLYTIC PROCESSING, FUNCTION,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=18422656; DOI=10.1111/j.1742-4658.2008.06404.x;
RA Lin Y., Stevens C., Hrstka R., Harrison B., Fourtouna A., Pathuri S.,
RA Vojtesek B., Hupp T.;
RT "An alternative transcript from the death-associated protein kinase 1 locus
RT encoding a small protein selectively mediates membrane blebbing.";
RL FEBS J. 275:2574-2584(2008).
RN [24]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH MAP1B.
RX PubMed=18195017; DOI=10.1074/jbc.m706040200;
RA Harrison B., Kraus M., Burch L., Stevens C., Craig A., Gordon-Weeks P.,
RA Hupp T.R.;
RT "DAPK-1 binding to a linear peptide motif in MAP1B stimulates autophagy and
RT membrane blebbing.";
RL J. Biol. Chem. 283:9999-10014(2008).
RN [25]
RP FUNCTION.
RX PubMed=18995835; DOI=10.1016/j.molcel.2008.09.019;
RA Mukhopadhyay R., Ray P.S., Arif A., Brady A.K., Kinter M., Fox P.L.;
RT "DAPK-ZIPK-L13a axis constitutes a negative-feedback module regulating
RT inflammatory gene expression.";
RL Mol. Cell 32:371-382(2008).
RN [26]
RP FUNCTION IN PHOSPHORYLATION OF BECN1, AND INTERACTION WITH BECN1.
RX PubMed=19180116; DOI=10.1038/embor.2008.246;
RA Zalckvar E., Berissi H., Mizrachy L., Idelchuk Y., Koren I., Eisenstein M.,
RA Sabanay H., Pinkas-Kramarski R., Kimchi A.;
RT "DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1 promotes
RT dissociation of beclin 1 from Bcl-XL and induction of autophagy.";
RL EMBO Rep. 10:285-292(2009).
RN [27]
RP FUNCTION IN PHOSPHORYLATION OF TSC2 AND RPS6, AND INTERACTION WITH TSC2.
RX PubMed=18974095; DOI=10.1074/jbc.m805165200;
RA Stevens C., Lin Y., Harrison B., Burch L., Ridgway R.A., Sansom O.,
RA Hupp T.;
RT "Peptide combinatorial libraries identify TSC2 as a death-associated
RT protein kinase (DAPK) death domain-binding protein and reveal a stimulatory
RT role for DAPK in mTORC1 signaling.";
RL J. Biol. Chem. 284:334-344(2009).
RN [28]
RP UBIQUITINATION, AND INTERACTION WITH KLHL20.
RX PubMed=20389280; DOI=10.1038/emboj.2010.62;
RA Lee Y.R., Yuan W.C., Ho H.C., Chen C.H., Shih H.M., Chen R.H.;
RT "The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquitination to
RT control interferon responses.";
RL EMBO J. 29:1748-1761(2010).
RN [29]
RP REVIEW ON FUNCTION.
RX PubMed=19878313; DOI=10.1111/j.1742-4658.2009.07411.x;
RA Lin Y., Hupp T.R., Stevens C.;
RT "Death-associated protein kinase (DAPK) and signal transduction: additional
RT roles beyond cell death.";
RL FEBS J. 277:48-57(2010).
RN [30]
RP FUNCTION IN PHOSPHORYLATION OF PIN1, AND INTERACTION WITH PIN1.
RX PubMed=21497122; DOI=10.1016/j.molcel.2011.03.005;
RA Lee T.H., Chen C.H., Suizu F., Huang P., Schiene-Fischer C., Daum S.,
RA Zhang Y.J., Goate A., Chen R.H., Zhou X.Z., Lu K.P.;
RT "Death-associated protein kinase 1 phosphorylates Pin1 and inhibits its
RT prolyl isomerase activity and cellular function.";
RL Mol. Cell 42:147-159(2011).
RN [31]
RP FUNCTION.
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 [32]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-333, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [33]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-319, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=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 [34]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-333, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [35]
RP INTERACTION WITH UNC5C.
RX PubMed=27068745; DOI=10.1074/jbc.m115.698092;
RA Hashimoto Y., Toyama Y., Kusakari S., Nawa M., Matsuoka M.;
RT "An Alzheimer Disease-linked Rare Mutation Potentiates Netrin Receptor
RT Uncoordinated-5C-induced Signaling That Merges with Amyloid beta Precursor
RT Protein Signaling.";
RL J. Biol. Chem. 291:12282-12293(2016).
RN [36]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 2-285 IN COMPLEX WITH ATP ANALOG
RP AND DIVALENT METAL CATION.
RX PubMed=11573098; DOI=10.1038/nsb1001-899;
RA Tereshko V., Teplova M., Brunzelle J., Watterson D.M., Egli M.;
RT "Crystal structures of the catalytic domain of human protein kinase
RT associated with apoptosis and tumor suppression.";
RL Nat. Struct. Biol. 8:899-907(2001).
RN [37]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 2-285 IN COMPLEX WITH SYNTHETIC
RP INHIBITOR.
RX PubMed=14505650; DOI=10.1016/s0960-894x(03)00733-9;
RA Velentza A.V., Wainwright M.S., Zasadzki M., Mirzoeva S., Schumacher A.M.,
RA Haiech J., Focia P.J., Egli M., Watterson D.M.;
RT "An aminopyridazine-based inhibitor of a pro-apoptotic protein kinase
RT attenuates hypoxia-ischemia induced acute brain injury.";
RL Bioorg. Med. Chem. Lett. 13:3465-3470(2003).
RN [38]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 1-278 IN COMPLEX WITH INHIBITORS.
RA Ueda Y., Ogata H., Yamakawa A., Higuchi Y.;
RT "Complex structure of kinase domain of DAP kinase with staurosporine.";
RL Submitted (APR-2006) to the PDB data bank.
RN [39]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 302-320 IN COMPLEX WITH
RP CALMODULIN.
RA Kursula P., Vahokoski J., Wilmanns M.;
RT "Recognition of human death-associated protein kinases by calmodulin.";
RL Submitted (JUL-2006) to the PDB data bank.
RN [40]
RP VARIANTS [LARGE SCALE ANALYSIS] ILE-416; SER-461; ALA-519; TYR-540;
RP THR-941; TRP-977; ASN-978; CYS-993; GLU-994; GLN-1005; TYR-1007; PRO-1008;
RP CYS-1010; ALA-1018; ILE-1272; ASN-1346 AND VAL-1405.
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 deaths signal, 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.
CC Phosphorylates PIN1 resulting in inhibition of its catalytic activity,
CC nuclear localization, and cellular function. Phosphorylates TPM1,
CC enhancing stress fiber formation in endothelial cells. Phosphorylates
CC STX1A and significantly decreases its binding to STXBP1. Phosphorylates
CC PRKD1 and regulates JNK signaling by binding and activating PRKD1 under
CC oxidative stress. Phosphorylates BECN1, reducing its interaction with
CC BCL2 and BCL2L1 and promoting the induction of autophagy.
CC Phosphorylates TSC2, disrupting the TSC1-TSC2 complex and stimulating
CC mTORC1 activity in a growth factor-dependent pathway. Phosphorylates
CC RPS6, MYL9 and DAPK3. Acts as a signaling amplifier of NMDA receptors
CC at extrasynaptic sites for mediating brain damage in stroke. Cerebral
CC ischemia recruits DAPK1 into the NMDA receptor complex and it
CC phosphorylates GRINB at Ser-1303 inducing injurious Ca(2+) influx
CC through NMDA receptor channels, resulting in an irreversible neuronal
CC death. Required together with DAPK3 for phosphorylation of RPL13A upon
CC interferon-gamma activation which is causing RPL13A involvement in
CC transcript-selective translation inhibition.
CC -!- FUNCTION: Isoform 2 cannot induce apoptosis but can induce membrane
CC blebbing.
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 -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- ACTIVITY REGULATION: Activated by Ca(2+)/calmodulin. Regulated by a
CC locking mechanism, involving autophosphorylation at Ser-308 and
CC calmodulin binding. In the inactive state, Ser-308 is phosphorylated.
CC Activation involves its dephosphorylation and a release-of-
CC autoinhibition mechanism where binding of calmodulin induces a
CC conformational change that relieves the steric block of the active site
CC by the autoinhibitory domain. Activity is modulated by UNC5B and NTN1.
CC UNC5B activates it by inhibiting the phosphorylation at Ser-308,
CC whereas NTN1 inhibits UNC5B-mediated activation of DAPK1. Endoplasmic-
CC stress activates by causing Ser-308 dephosphorylation.
CC {ECO:0000269|PubMed:11579085, ECO:0000269|PubMed:15729359,
CC ECO:0000269|PubMed:17056602}.
CC -!- SUBUNIT: Interacts with KLHL20 (PubMed:20389280). Interacts (via death
CC domain) with MAPK1 and MAPK3 (PubMed:15616583). Interacts with MAP1B
CC (via N-terminus) (PubMed:18195017). Interacts with PRKD1 in an
CC oxidative stress-regulated manner (PubMed:17703233). Interacts with
CC PIN1, PDCD6, BECN1, TSC2 and STX1A (PubMed:12730201, PubMed:16132846,
CC PubMed:18974095, PubMed:19180116, PubMed:21497122). Interacts (via
CC kinase domain) with DAPK3 (via kinase domain) (PubMed:15367680).
CC Interacts with GRINB (By similarity). Interacts (via death domain) with
CC UNC5B (via death domain) (PubMed:15729359). Interacts with UNC5C (via
CC death domain) (PubMed:27068745). {ECO:0000250|UniProtKB:Q80YE7,
CC ECO:0000269|PubMed:12730201, ECO:0000269|PubMed:15367680,
CC ECO:0000269|PubMed:15616583, ECO:0000269|PubMed:15729359,
CC ECO:0000269|PubMed:16132846, ECO:0000269|PubMed:17703233,
CC ECO:0000269|PubMed:18195017, ECO:0000269|PubMed:18974095,
CC ECO:0000269|PubMed:19180116, ECO:0000269|PubMed:20389280,
CC ECO:0000269|PubMed:21497122, ECO:0000269|PubMed:27068745}.
CC -!- INTERACTION:
CC P53355; O95816: BAG2; NbExp=3; IntAct=EBI-358616, EBI-355275;
CC P53355; Q14457: BECN1; NbExp=4; IntAct=EBI-358616, EBI-949378;
CC P53355; P62158: CALM3; NbExp=6; IntAct=EBI-358616, EBI-397435;
CC P53355; P53355: DAPK1; NbExp=6; IntAct=EBI-358616, EBI-358616;
CC P53355; Q9Y2M5: KLHL20; NbExp=11; IntAct=EBI-358616, EBI-714379;
CC P53355; Q9UHB6: LIMA1; NbExp=2; IntAct=EBI-358616, EBI-351479;
CC P53355; Q38SD2: LRRK1; NbExp=2; IntAct=EBI-358616, EBI-1050422;
CC P53355; Q5S007: LRRK2; NbExp=2; IntAct=EBI-358616, EBI-5323863;
CC P53355; P27361: MAPK3; NbExp=5; IntAct=EBI-358616, EBI-73995;
CC P53355; O75340: PDCD6; NbExp=3; IntAct=EBI-358616, EBI-352915;
CC P53355; P14618: PKM; NbExp=3; IntAct=EBI-358616, EBI-353408;
CC P53355; P14618-1: PKM; NbExp=2; IntAct=EBI-358616, EBI-4304679;
CC P53355; P63151: PPP2R2A; NbExp=3; IntAct=EBI-358616, EBI-1048931;
CC P53355; Q9UNE7: STUB1; NbExp=2; IntAct=EBI-358616, EBI-357085;
CC -!- SUBCELLULAR LOCATION: [Isoform 1]: Cytoplasm. Cytoplasm, cytoskeleton.
CC Note=Colocalizes with MAP1B in the microtubules and cortical actin
CC fibers.
CC -!- SUBCELLULAR LOCATION: [Isoform 2]: Cytoplasm. Cytoplasm, cytoskeleton.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Name=1; Synonyms=Alpha;
CC IsoId=P53355-1; Sequence=Displayed;
CC Name=2; Synonyms=s-DAPK-1;
CC IsoId=P53355-2; Sequence=VSP_042053, VSP_042054, VSP_042055;
CC Name=3; Synonyms=Beta;
CC IsoId=P53355-3; Sequence=VSP_042056;
CC Name=4;
CC IsoId=P53355-4; Sequence=VSP_054478;
CC -!- TISSUE SPECIFICITY: Isoform 2 is expressed in normal intestinal tissue
CC as well as in colorectal carcinomas. {ECO:0000269|PubMed:18422656}.
CC -!- INDUCTION: Up-regulated following treatment with IFNG/IFN-gamma.
CC {ECO:0000269|PubMed:7828849}.
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: Ubiquitinated by the BCR(KLHL20) E3 ubiquitin ligase complex,
CC leading to its degradation by the proteasome.
CC {ECO:0000269|PubMed:20389280}.
CC -!- PTM: Removal of the C-terminal tail of isoform 2 (corresponding to
CC amino acids 296-337 of isoform 2) by proteolytic cleavage stimulates
CC maximally its membrane-blebbing function.
CC {ECO:0000269|PubMed:18422656}.
CC -!- PTM: In response to mitogenic stimulation (PMA or EGF), phosphorylated
CC at Ser-289; phosphorylation suppresses DAPK1 pro-apoptotic function.
CC Autophosphorylation at Ser-308 inhibits its catalytic activity.
CC Phosphorylation at Ser-734 by MAPK1 increases its catalytic activity
CC and promotes cytoplasmic retention of MAPK1. Endoplasmic-stress can
CC cause dephosphorylation at Ser-308. {ECO:0000269|PubMed:11579085,
CC ECO:0000269|PubMed:15616583, ECO:0000269|PubMed:15729359,
CC ECO:0000269|PubMed:16213824, ECO:0000269|PubMed:17056602}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. DAP kinase subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAP35581.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the C-terminal part.; Evidence={ECO:0000305};
CC Sequence=CAA53712.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/dapk1/";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/DAPK1ID417ch9q21.html";
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DR EMBL; X76104; CAA53712.1; ALT_FRAME; mRNA.
DR EMBL; AK127855; BAC87163.1; -; mRNA.
DR EMBL; CR749834; CAH18690.1; -; mRNA.
DR EMBL; DQ436495; ABD96827.1; -; Genomic_DNA.
DR EMBL; AL160279; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL161787; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL591852; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471089; EAW62727.1; -; Genomic_DNA.
DR EMBL; BC113660; AAI13661.1; -; mRNA.
DR EMBL; BC143733; AAI43734.1; -; mRNA.
DR EMBL; BC143759; AAI43760.1; -; mRNA.
DR EMBL; BT006935; AAP35581.1; ALT_SEQ; mRNA.
DR CCDS; CCDS43842.1; -. [P53355-1]
DR PIR; I37275; I37275.
DR RefSeq; NP_001275658.1; NM_001288729.1. [P53355-1]
DR RefSeq; NP_001275659.1; NM_001288730.1. [P53355-1]
DR RefSeq; NP_001275660.1; NM_001288731.1. [P53355-1]
DR RefSeq; NP_004929.2; NM_004938.3. [P53355-1]
DR PDB; 1IG1; X-ray; 1.80 A; A=2-285.
DR PDB; 1JKK; X-ray; 2.40 A; A=2-285.
DR PDB; 1JKL; X-ray; 1.62 A; A=2-285.
DR PDB; 1JKS; X-ray; 1.50 A; A=2-285.
DR PDB; 1JKT; X-ray; 3.50 A; A/B=2-285.
DR PDB; 1P4F; X-ray; 1.90 A; A=2-285.
DR PDB; 1WVW; X-ray; 2.40 A; A=1-278.
DR PDB; 1WVX; X-ray; 2.60 A; A=1-278.
DR PDB; 1WVY; X-ray; 2.80 A; A=1-278.
DR PDB; 1YR5; X-ray; 1.70 A; B=302-320.
DR PDB; 2W4J; X-ray; 1.30 A; A=1-277.
DR PDB; 2W4K; X-ray; 1.90 A; A=1-302.
DR PDB; 2X0G; X-ray; 2.20 A; A=1-334.
DR PDB; 2XUU; X-ray; 1.80 A; A=1-334.
DR PDB; 2XZS; X-ray; 2.00 A; A/B=2-312.
DR PDB; 2Y0A; X-ray; 2.60 A; A=2-304.
DR PDB; 2Y4P; X-ray; 2.65 A; A/B/C/D=1-285.
DR PDB; 2Y4V; X-ray; 1.80 A; B=302-320.
DR PDB; 2YAK; X-ray; 2.20 A; A=1-285.
DR PDB; 3DFC; X-ray; 1.90 A; B=1-285.
DR PDB; 3DGK; X-ray; 1.70 A; A=1-285.
DR PDB; 3EH9; X-ray; 1.70 A; A=2-285.
DR PDB; 3EHA; X-ray; 1.60 A; A=2-285.
DR PDB; 3F5G; X-ray; 1.85 A; A=2-285.
DR PDB; 3F5U; X-ray; 2.00 A; A=1-285.
DR PDB; 3GU4; X-ray; 1.35 A; A=1-285.
DR PDB; 3GU5; X-ray; 1.65 A; A=1-285.
DR PDB; 3GU6; X-ray; 1.49 A; A=1-285.
DR PDB; 3GU7; X-ray; 1.90 A; A=1-285.
DR PDB; 3GU8; X-ray; 1.60 A; A=1-285.
DR PDB; 3GUB; X-ray; 1.71 A; A=1-285.
DR PDB; 3ZXT; X-ray; 2.65 A; A/B/C/D=1-285.
DR PDB; 4B4L; X-ray; 1.75 A; A=1-334.
DR PDB; 4PF4; X-ray; 1.13 A; A=1-277.
DR PDB; 4TL0; X-ray; 2.70 A; A=1-334.
DR PDB; 4TXC; X-ray; 1.95 A; A=1-285.
DR PDB; 4UV0; X-ray; 2.49 A; A=1-321.
DR PDB; 4YO4; X-ray; 1.60 A; A=2-285.
DR PDB; 4YPD; X-ray; 1.40 A; A=2-285.
DR PDB; 5AUT; X-ray; 1.70 A; A=1-285.
DR PDB; 5AUU; X-ray; 1.70 A; A=1-285.
DR PDB; 5AUV; X-ray; 1.50 A; A=1-285.
DR PDB; 5AUW; X-ray; 1.50 A; A=1-285.
DR PDB; 5AUX; X-ray; 1.50 A; A=1-285.
DR PDB; 5AUY; X-ray; 2.00 A; A=1-285.
DR PDB; 5AUZ; X-ray; 1.60 A; A=1-285.
DR PDB; 5AV0; X-ray; 1.85 A; A=1-285.
DR PDB; 5AV1; X-ray; 1.50 A; A=1-285.
DR PDB; 5AV2; X-ray; 1.50 A; A=1-285.
DR PDB; 5AV3; X-ray; 1.90 A; A=1-285.
DR PDB; 5AV4; X-ray; 1.40 A; A=1-285.
DR PDB; 6AAR; X-ray; 1.95 A; A=1-285.
DR PDB; 6FHA; X-ray; 2.30 A; A=2-334.
DR PDB; 6FHB; X-ray; 1.75 A; A=2-334.
DR PDB; 6GY5; X-ray; 1.09 A; U=1334-1344.
DR PDB; 6IN4; X-ray; 1.80 A; A=1-285.
DR PDB; 6QMO; X-ray; 1.87 A; A=2-310.
DR PDB; 6QN4; X-ray; 2.50 A; A=2-310.
DR PDB; 7CCU; X-ray; 1.65 A; A=1-285.
DR PDB; 7CCV; X-ray; 1.75 A; A=1-285.
DR PDB; 7CCW; X-ray; 1.40 A; A=1-285.
DR PDBsum; 1IG1; -.
DR PDBsum; 1JKK; -.
DR PDBsum; 1JKL; -.
DR PDBsum; 1JKS; -.
DR PDBsum; 1JKT; -.
DR PDBsum; 1P4F; -.
DR PDBsum; 1WVW; -.
DR PDBsum; 1WVX; -.
DR PDBsum; 1WVY; -.
DR PDBsum; 1YR5; -.
DR PDBsum; 2W4J; -.
DR PDBsum; 2W4K; -.
DR PDBsum; 2X0G; -.
DR PDBsum; 2XUU; -.
DR PDBsum; 2XZS; -.
DR PDBsum; 2Y0A; -.
DR PDBsum; 2Y4P; -.
DR PDBsum; 2Y4V; -.
DR PDBsum; 2YAK; -.
DR PDBsum; 3DFC; -.
DR PDBsum; 3DGK; -.
DR PDBsum; 3EH9; -.
DR PDBsum; 3EHA; -.
DR PDBsum; 3F5G; -.
DR PDBsum; 3F5U; -.
DR PDBsum; 3GU4; -.
DR PDBsum; 3GU5; -.
DR PDBsum; 3GU6; -.
DR PDBsum; 3GU7; -.
DR PDBsum; 3GU8; -.
DR PDBsum; 3GUB; -.
DR PDBsum; 3ZXT; -.
DR PDBsum; 4B4L; -.
DR PDBsum; 4PF4; -.
DR PDBsum; 4TL0; -.
DR PDBsum; 4TXC; -.
DR PDBsum; 4UV0; -.
DR PDBsum; 4YO4; -.
DR PDBsum; 4YPD; -.
DR PDBsum; 5AUT; -.
DR PDBsum; 5AUU; -.
DR PDBsum; 5AUV; -.
DR PDBsum; 5AUW; -.
DR PDBsum; 5AUX; -.
DR PDBsum; 5AUY; -.
DR PDBsum; 5AUZ; -.
DR PDBsum; 5AV0; -.
DR PDBsum; 5AV1; -.
DR PDBsum; 5AV2; -.
DR PDBsum; 5AV3; -.
DR PDBsum; 5AV4; -.
DR PDBsum; 6AAR; -.
DR PDBsum; 6FHA; -.
DR PDBsum; 6FHB; -.
DR PDBsum; 6GY5; -.
DR PDBsum; 6IN4; -.
DR PDBsum; 6QMO; -.
DR PDBsum; 6QN4; -.
DR PDBsum; 7CCU; -.
DR PDBsum; 7CCV; -.
DR PDBsum; 7CCW; -.
DR AlphaFoldDB; P53355; -.
DR SMR; P53355; -.
DR BioGRID; 107982; 149.
DR ComplexPortal; CPX-102; DAPK1 - calmodulin complex.
DR IntAct; P53355; 171.
DR MINT; P53355; -.
DR STRING; 9606.ENSP00000386135; -.
DR BindingDB; P53355; -.
DR ChEMBL; CHEMBL2558; -.
DR DrugBank; DB04069; 5,6-Dihydro-Benzo[H]Cinnolin-3-Ylamine.
DR DrugBank; DB07444; 6-(3-AMINOPROPYL)-4,9-DIMETHYLPYRROLO[3,4-C]CARBAZOLE-1,3(2H,6H)-DIONE.
DR DrugBank; DB12010; Fostamatinib.
DR DrugBank; DB04395; Phosphoaminophosphonic Acid-Adenylate Ester.
DR DrugCentral; P53355; -.
DR GuidetoPHARMACOLOGY; 2002; -.
DR iPTMnet; P53355; -.
DR PhosphoSitePlus; P53355; -.
DR BioMuta; DAPK1; -.
DR DMDM; 317373595; -.
DR EPD; P53355; -.
DR jPOST; P53355; -.
DR MassIVE; P53355; -.
DR MaxQB; P53355; -.
DR PaxDb; P53355; -.
DR PeptideAtlas; P53355; -.
DR PRIDE; P53355; -.
DR ProteomicsDB; 56570; -. [P53355-1]
DR ProteomicsDB; 56571; -. [P53355-2]
DR ProteomicsDB; 56572; -. [P53355-3]
DR ProteomicsDB; 7221; -.
DR Antibodypedia; 6771; 416 antibodies from 37 providers.
DR DNASU; 1612; -.
DR Ensembl; ENST00000358077.9; ENSP00000350785.5; ENSG00000196730.13. [P53355-1]
DR Ensembl; ENST00000408954.8; ENSP00000386135.3; ENSG00000196730.13. [P53355-1]
DR Ensembl; ENST00000469640.6; ENSP00000418885.3; ENSG00000196730.13. [P53355-4]
DR Ensembl; ENST00000472284.5; ENSP00000417076.1; ENSG00000196730.13. [P53355-1]
DR Ensembl; ENST00000491893.5; ENSP00000419026.1; ENSG00000196730.13. [P53355-4]
DR Ensembl; ENST00000622514.4; ENSP00000484267.1; ENSG00000196730.13. [P53355-1]
DR GeneID; 1612; -.
DR KEGG; hsa:1612; -.
DR MANE-Select; ENST00000408954.8; ENSP00000386135.3; NM_004938.4; NP_004929.2.
DR UCSC; uc004apc.5; human. [P53355-1]
DR CTD; 1612; -.
DR DisGeNET; 1612; -.
DR GeneCards; DAPK1; -.
DR HGNC; HGNC:2674; DAPK1.
DR HPA; ENSG00000196730; Low tissue specificity.
DR MIM; 600831; gene.
DR neXtProt; NX_P53355; -.
DR OpenTargets; ENSG00000196730; -.
DR PharmGKB; PA27142; -.
DR VEuPathDB; HostDB:ENSG00000196730; -.
DR eggNOG; KOG0032; Eukaryota.
DR GeneTree; ENSGT00940000153424; -.
DR HOGENOM; CLU_002849_2_0_1; -.
DR InParanoid; P53355; -.
DR OrthoDB; 67579at2759; -.
DR PhylomeDB; P53355; -.
DR TreeFam; TF314166; -.
DR BRENDA; 2.7.11.1; 2681.
DR PathwayCommons; P53355; -.
DR Reactome; R-HSA-418889; Caspase activation via Dependence Receptors in the absence of ligand.
DR SignaLink; P53355; -.
DR SIGNOR; P53355; -.
DR BioGRID-ORCS; 1612; 14 hits in 1114 CRISPR screens.
DR ChiTaRS; DAPK1; human.
DR EvolutionaryTrace; P53355; -.
DR GeneWiki; DAPK1; -.
DR GenomeRNAi; 1612; -.
DR Pharos; P53355; Tchem.
DR PRO; PR:P53355; -.
DR Proteomes; UP000005640; Chromosome 9.
DR RNAct; P53355; protein.
DR Bgee; ENSG00000196730; Expressed in germinal epithelium of ovary and 192 other tissues.
DR ExpressionAtlas; P53355; baseline and differential.
DR Genevisible; P53355; HS.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:1990722; C:DAPK1-calmodulin complex; IPI:ComplexPortal.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0005516; F:calmodulin binding; IDA:UniProtKB.
DR GO; GO:0004683; F:calmodulin-dependent protein kinase activity; IDA:UniProtKB.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0042802; F:identical protein binding; IPI:IntAct.
DR GO; GO:0004672; F:protein kinase activity; IDA:UniProtKB.
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:0017075; F:syntaxin-1 binding; IPI:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; IMP:UniProtKB.
DR GO; GO:0097190; P:apoptotic signaling pathway; IMP:UniProtKB.
DR GO; GO:0071447; P:cellular response to hydroperoxide; IMP:ParkinsonsUK-UCL.
DR GO; GO:0071346; P:cellular response to interferon-gamma; IDA:UniProtKB.
DR GO; GO:0002357; P:defense response to tumor cell; IMP:ARUK-UCL.
DR GO; GO:0008625; P:extrinsic apoptotic signaling pathway via death domain receptors; IEA:Ensembl.
DR GO; GO:0035556; P:intracellular signal transduction; IDA:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0017148; P:negative regulation of translation; IDA:UniProtKB.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:ComplexPortal.
DR GO; GO:1904094; P:positive regulation of autophagic cell death; IMP:ComplexPortal.
DR GO; GO:0010508; P:positive regulation of autophagy; IMP:ParkinsonsUK-UCL.
DR GO; GO:0043280; P:positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; IDA:UniProtKB.
DR GO; GO:0046777; P:protein autophosphorylation; IDA: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:2000310; P:regulation of NMDA receptor activity; ISS:UniProtKB.
DR GO; GO:0002834; P:regulation of response to tumor cell; IDA:ComplexPortal.
DR Gene3D; 1.10.533.10; -; 1.
DR Gene3D; 1.25.40.20; -; 3.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR002110; Ankyrin_rpt.
DR InterPro; IPR036770; Ankyrin_rpt-contain_sf.
DR InterPro; IPR020676; DAPK1.
DR InterPro; IPR011029; DEATH-like_dom_sf.
DR InterPro; IPR000488; Death_domain.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR020859; ROC_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR PANTHER; PTHR24342:SF17; PTHR24342:SF17; 1.
DR Pfam; PF00023; Ank; 1.
DR Pfam; PF12796; Ank_2; 2.
DR Pfam; PF13637; Ank_4; 1.
DR Pfam; PF00531; Death; 1.
DR Pfam; PF00069; Pkinase; 1.
DR PRINTS; PR01415; ANKYRIN.
DR SMART; SM00248; ANK; 9.
DR SMART; SM00005; DEATH; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF47986; SSF47986; 1.
DR SUPFAM; SSF48403; SSF48403; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50297; ANK_REP_REGION; 1.
DR PROSITE; PS50088; ANK_REPEAT; 7.
DR PROSITE; PS50017; DEATH_DOMAIN; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS51424; ROC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; ANK repeat; Apoptosis; ATP-binding;
KW Calmodulin-binding; Cytoplasm; Cytoskeleton; GTP-binding; Kinase;
KW Nucleotide-binding; Phosphoprotein; Reference proteome; Repeat;
KW Serine/threonine-protein kinase; Transferase; Translation regulation;
KW Ubl conjugation.
FT CHAIN 1..1430
FT /note="Death-associated protein kinase 1"
FT /id="PRO_0000085910"
FT DOMAIN 13..275
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REPEAT 378..407
FT /note="ANK 1"
FT REPEAT 411..440
FT /note="ANK 2"
FT REPEAT 444..473
FT /note="ANK 3"
FT REPEAT 477..506
FT /note="ANK 4"
FT REPEAT 510..539
FT /note="ANK 5"
FT REPEAT 543..572
FT /note="ANK 6"
FT REPEAT 576..605
FT /note="ANK 7"
FT REPEAT 609..638
FT /note="ANK 8"
FT DOMAIN 681..955
FT /note="Roc"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00758"
FT REPEAT 875..904
FT /note="ANK 9"
FT REPEAT 1162..1196
FT /note="ANK 10"
FT DOMAIN 1312..1396
FT /note="Death"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00064"
FT REGION 267..334
FT /note="Calmodulin-binding"
FT REGION 292..301
FT /note="Autoinhibitory domain"
FT /evidence="ECO:0000250"
FT ACT_SITE 139
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 19..27
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 42
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 94..96
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 100
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT BINDING 161
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT MOD_RES 289
FT /note="Phosphoserine; by RPS6KA1 and RPS6KA3"
FT /evidence="ECO:0000269|PubMed:16213824"
FT MOD_RES 308
FT /note="Phosphoserine; by autocatalysis"
FT /evidence="ECO:0000269|PubMed:11579085,
FT ECO:0000269|PubMed:15729359, ECO:0000269|PubMed:17056602"
FT MOD_RES 319
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 333
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:24275569"
FT MOD_RES 734
FT /note="Phosphoserine; by MAPK1"
FT /evidence="ECO:0000269|PubMed:15616583"
FT MOD_RES 1115
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q80YE7"
FT VAR_SEQ 1..446
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042053"
FT VAR_SEQ 742..783
FT /note="VSVSINNLYPGCENVSVRSRSMMFEPGLTKGMLEVFVAPTHH -> GRNLHA
FT GPVSPAGVGFRTLSFQGLGGKGVVFGSLGLYWTLWP (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042054"
FT VAR_SEQ 784..1430
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042055"
FT VAR_SEQ 805..870
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_054478"
FT VAR_SEQ 1430
FT /note="R -> RRNSHVWNPTV (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_042056"
FT VARIANT 416
FT /note="V -> I (in dbSNP:rs12343465)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_033235"
FT VARIANT 461
FT /note="A -> S"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040420"
FT VARIANT 519
FT /note="S -> A"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040421"
FT VARIANT 540
FT /note="C -> Y (in dbSNP:rs56327474)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040422"
FT VARIANT 591
FT /note="P -> L (in dbSNP:rs36214022)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_060693"
FT VARIANT 622
FT /note="I -> M (in dbSNP:rs36215047)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_060694"
FT VARIANT 941
FT /note="M -> T"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040423"
FT VARIANT 977
FT /note="R -> W"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040424"
FT VARIANT 978
FT /note="K -> N"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040425"
FT VARIANT 993
FT /note="Y -> C"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040426"
FT VARIANT 994
FT /note="D -> E"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040427"
FT VARIANT 1005
FT /note="E -> Q"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040428"
FT VARIANT 1007
FT /note="D -> Y"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040429"
FT VARIANT 1008
FT /note="L -> P"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040430"
FT VARIANT 1010
FT /note="R -> C (in dbSNP:rs371784492)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040431"
FT VARIANT 1018
FT /note="T -> A"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040432"
FT VARIANT 1272
FT /note="M -> I (in dbSNP:rs56169226)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040433"
FT VARIANT 1346
FT /note="S -> N (in dbSNP:rs1056719)"
FT /evidence="ECO:0000269|PubMed:15164053,
FT ECO:0000269|PubMed:17344846, ECO:0000269|PubMed:17974005,
FT ECO:0000269|PubMed:7828849, ECO:0000269|Ref.5"
FT /id="VAR_040434"
FT VARIANT 1405
FT /note="G -> V (in dbSNP:rs36220450)"
FT /evidence="ECO:0000269|PubMed:17344846, ECO:0000269|Ref.5"
FT /id="VAR_040435"
FT MUTAGEN 42
FT /note="K->A: Loss of activity, apoptotic function and of
FT autophosphorylation."
FT /evidence="ECO:0000269|PubMed:11579085,
FT ECO:0000269|PubMed:7828849"
FT MUTAGEN 289
FT /note="S->A: Loss of phosphorylation and significant
FT increase in proapoptotic activity."
FT MUTAGEN 289
FT /note="S->E: Reduction in proapoptotic activity."
FT MUTAGEN 308
FT /note="S->A: Elevated Ca(2+)-calmodulin binding and Ca(2+)-
FT calmodulin-independent kinase activity. Increases apoptotic
FT activity."
FT /evidence="ECO:0000269|PubMed:11579085"
FT MUTAGEN 308
FT /note="S->D: Reduced Ca(2+)-calmodulin binding and Ca(2+)-
FT calmodulin-independent kinase activity. Decreases apoptotic
FT activity."
FT /evidence="ECO:0000269|PubMed:11579085"
FT MUTAGEN 313
FT /note="S->A: Minimal effect on activity."
FT /evidence="ECO:0000269|PubMed:11579085"
FT CONFLICT 490
FT /note="Y -> H (in Ref. 3; BAC87163)"
FT /evidence="ECO:0000305"
FT CONFLICT 1217
FT /note="S -> G (in Ref. 4; CAH18690)"
FT /evidence="ECO:0000305"
FT HELIX 9..11
FT /evidence="ECO:0007829|PDB:4PF4"
FT STRAND 13..21
FT /evidence="ECO:0007829|PDB:4PF4"
FT STRAND 23..32
FT /evidence="ECO:0007829|PDB:4PF4"
FT TURN 33..35
FT /evidence="ECO:0007829|PDB:4PF4"
FT STRAND 38..46
FT /evidence="ECO:0007829|PDB:4PF4"
FT STRAND 48..51
FT /evidence="ECO:0007829|PDB:2W4J"
FT STRAND 53..56
FT /evidence="ECO:0007829|PDB:4PF4"
FT HELIX 58..70
FT /evidence="ECO:0007829|PDB:4PF4"
FT STRAND 79..84
FT /evidence="ECO:0007829|PDB:4PF4"
FT STRAND 86..94
FT /evidence="ECO:0007829|PDB:4PF4"
FT HELIX 101..107
FT /evidence="ECO:0007829|PDB:4PF4"
FT STRAND 108..110
FT /evidence="ECO:0007829|PDB:3ZXT"
FT HELIX 113..132
FT /evidence="ECO:0007829|PDB:4PF4"
FT STRAND 134..136
FT /evidence="ECO:0007829|PDB:1JKT"
FT HELIX 142..144
FT /evidence="ECO:0007829|PDB:4PF4"
FT STRAND 145..148
FT /evidence="ECO:0007829|PDB:4PF4"
FT STRAND 150..154
FT /evidence="ECO:0007829|PDB:4PF4"
FT STRAND 157..159
FT /evidence="ECO:0007829|PDB:4PF4"
FT HELIX 162..164
FT /evidence="ECO:0007829|PDB:4UV0"
FT STRAND 169..171
FT /evidence="ECO:0007829|PDB:2W4J"
FT HELIX 181..183
FT /evidence="ECO:0007829|PDB:4PF4"
FT HELIX 186..189
FT /evidence="ECO:0007829|PDB:4PF4"
FT HELIX 197..212
FT /evidence="ECO:0007829|PDB:4PF4"
FT HELIX 222..230
FT /evidence="ECO:0007829|PDB:4PF4"
FT HELIX 238..241
FT /evidence="ECO:0007829|PDB:4PF4"
FT STRAND 242..244
FT /evidence="ECO:0007829|PDB:1P4F"
FT HELIX 246..255
FT /evidence="ECO:0007829|PDB:4PF4"
FT TURN 260..262
FT /evidence="ECO:0007829|PDB:4PF4"
FT HELIX 266..271
FT /evidence="ECO:0007829|PDB:4PF4"
FT TURN 273..275
FT /evidence="ECO:0007829|PDB:4PF4"
FT HELIX 280..288
FT /evidence="ECO:0007829|PDB:4B4L"
FT HELIX 293..302
FT /evidence="ECO:0007829|PDB:4B4L"
FT HELIX 304..318
FT /evidence="ECO:0007829|PDB:1YR5"
FT TURN 1338..1340
FT /evidence="ECO:0007829|PDB:6GY5"
SQ SEQUENCE 1430 AA; 160046 MW; E2C4246E7C78A6D2 CRC64;
MTVFRQENVD DYYDTGEELG SGQFAVVKKC REKSTGLQYA AKFIKKRRTK SSRRGVSRED
IEREVSILKE IQHPNVITLH EVYENKTDVI LILELVAGGE LFDFLAEKES LTEEEATEFL
KQILNGVYYL HSLQIAHFDL KPENIMLLDR NVPKPRIKII DFGLAHKIDF GNEFKNIFGT
PEFVAPEIVN YEPLGLEADM WSIGVITYIL LSGASPFLGD TKQETLANVS AVNYEFEDEY
FSNTSALAKD FIRRLLVKDP KKRMTIQDSL QHPWIKPKDT QQALSRKASA VNMEKFKKFA
ARKKWKQSVR LISLCQRLSR SFLSRSNMSV ARSDDTLDEE DSFVMKAIIH AINDDNVPGL
QHLLGSLSNY DVNQPNKHGT PPLLIAAGCG NIQILQLLIK RGSRIDVQDK GGSNAVYWAA
RHGHVDTLKF LSENKCPLDV KDKSGEMALH VAARYGHADV AQLLCSFGSN PNIQDKEEET
PLHCAAWHGY YSVAKALCEA GCNVNIKNRE GETPLLTASA RGYHDIVECL AEHGADLNAC
DKDGHIALHL AVRRCQMEVI KTLLSQGCFV DYQDRHGNTP LHVACKDGNM PIVVALCEAN
CNLDISNKYG RTPLHLAANN GILDVVRYLC LMGASVEALT TDGKTAEDLA RSEQHEHVAG
LLARLRKDTH RGLFIQQLRP TQNLQPRIKL KLFGHSGSGK TTLVESLKCG LLRSFFRRRR
PRLSSTNSSR FPPSPLASKP TVSVSINNLY PGCENVSVRS RSMMFEPGLT KGMLEVFVAP
THHPHCSADD QSTKAIDIQN AYLNGVGDFS VWEFSGNPVY FCCYDYFAAN DPTSIHVVVF
SLEEPYEIQL NQVIFWLSFL KSLVPVEEPI AFGGKLKNPL QVVLVATHAD IMNVPRPAGG
EFGYDKDTSL LKEIRNRFGN DLHISNKLFV LDAGASGSKD MKVLRNHLQE IRSQIVSVCP
PMTHLCEKII STLPSWRKLN GPNQLMSLQQ FVYDVQDQLN PLASEEDLRR IAQQLHSTGE
INIMQSETVQ DVLLLDPRWL CTNVLGKLLS VETPRALHHY RGRYTVEDIQ RLVPDSDVEE
LLQILDAMDI CARDLSSGTM VDVPALIKTD NLHRSWADEE DEVMVYGGVR IVPVEHLTPF
PCGIFHKVQV NLCRWIHQQS TEGDADIRLW VNGCKLANRG AELLVLLVNH GQGIEVQVRG
LETEKIKCCL LLDSVCSTIE NVMATTLPGL LTVKHYLSPQ QLREHHEPVM IYQPRDFFRA
QTLKETSLTN TMGGYKESFS SIMCFGCHDV YSQASLGMDI HASDLNLLTR RKLSRLLDPP
DPLGKDWCLL AMNLGLPDLV AKYNTSNGAP KDFLPSPLHA LLREWTTYPE STVGTLMSKL
RELGRRDAAD FLLKASSVFK INLDGNGQEA YASSCNSGTS YNSISSVVSR
