DAPK1

Death-associated protein kinase 1

PDB rendering based on 1ig1.

Available structures

Ortholog search: PDBe, RCSB

List of PDB id codes
1IG1, 1JKK, 1JKL, 1JKS, 1JKT, 1P4F, 1WVW, 1WVX, 1WVY, 1YR5, 2W4J, 2W4K, 2X0G, 2XUU, 2XZS, 2Y0A, 2Y4P, 2Y4V, 2YAK, 3DFC, 3DGK, 3EH9, 3EHA, 3F5G, 3F5U, 3GU4, 3GU5, 3GU6, 3GU7, 3GU8, 3GUB, 3ZXT, 4B4L, 4PF4, 4TXC, 4YO4, 4YPD

Identifiers

Symbols

DAPK1 ; DAPK

External IDs

OMIM: 600831 MGI: 1916885 HomoloGene: 3626 ChEMBL: 2558 GeneCards: DAPK1 Gene

EC number

2.7.11.1

Gene ontology
Molecular function	• protein kinase activity • protein serine/threonine kinase activity • calmodulin-dependent protein kinase activity • protein binding • calmodulin binding • ATP binding • GTP binding • syntaxin-1 binding • identical protein binding
Cellular component	• cytoplasm • plasma membrane • actin cytoskeleton
Biological process	• protein phosphorylation • apoptotic process • extrinsic apoptotic signaling pathway via death domain receptors • regulation of autophagy • programmed cell death • negative regulation of translation • intracellular signal transduction • regulation of apoptotic process • positive regulation of cysteine-type endopeptidase activity involved in apoptotic process • protein autophosphorylation • cellular response to interferon-gamma • apoptotic signaling pathway • extrinsic apoptotic signaling pathway • extrinsic apoptotic signaling pathway in absence of ligand • negative regulation of extrinsic apoptotic signaling pathway via death domain receptors • regulation of N-methyl-D-aspartate selective glutamate receptor activity
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 9:
87.5 – 87.71 Mb

Chr 13:
60.6 – 60.76 Mb

PubMed search

Death-associated protein kinase 1 is an enzyme that in humans is encoded by the DAPK1 gene.^[1]

Function

Death-associated protein kinase 1 is a positive mediator of gamma-interferon induced programmed cell death. DAPK1 encodes a structurally unique 160-kD calmodulin dependent serine-threonine kinase that carries 8 ankyrin repeats and 2 putative P-loop consensus sites. It is a tumor suppressor candidate.^[2]

In melanocytic cells DAPK1 gene expression may be regulated by MITF.^[3]

As a drug target

Depletion of DAPK1 results in inhibition of tumor cell count and volume growth in cellular and animal models of triple receptor-negative breast cancer, from individuals with p53-mutant cancers.^[4] This has not been demonstrated in actual patients.

References

↑ Feinstein E, Druck T, Kastury K, Berissi H, Goodart SA, Overhauser J, Kimchi A, Huebner K (Sep 1995). "Assignment of DAP1 and DAPK--genes that positively mediate programmed cell death triggered by IFN-gamma--to chromosome regions 5p12.2 and 9q34.1, respectively". Genomics 29 (1): 305–7. doi:10.1006/geno.1995.1255. PMID 8530096.
↑ "Entrez Gene: DAPK1 death-associated protein kinase 1".
↑ Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E (Dec 2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell & Melanoma Research 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.
↑ Zhao J, Zhao D, Poage GM, Mazumdar A, Zhang Y, Hill JL, Hartman ZC, Savage MI, Mills GB, Brown PH (Jul 2015). "Death-associated protein kinase 1 promotes growth of p53-mutant cancers". The Journal of Clinical Investigation 125 (7): 2707–20. doi:10.1172/JCI70805. PMID 26075823.

Deiss LP, Feinstein E, Berissi H, Cohen O, Kimchi A (Jan 1995). "Identification of a novel serine/threonine kinase and a novel 15-kD protein as potential mediators of the gamma interferon-induced cell death". Genes & Development 9 (1): 15–30. doi:10.1101/gad.9.1.15. PMID 7828849.
Inbal B, Shani G, Cohen O, Kissil JL, Kimchi A (Feb 2000). "Death-associated protein kinase-related protein 1, a novel serine/threonine kinase involved in apoptosis". Molecular and Cellular Biology 20 (3): 1044–54. doi:10.1128/MCB.20.3.1044-1054.2000. PMC 85221. PMID 10629061.
Jin Y, Blue EK, Dixon S, Hou L, Wysolmerski RB, Gallagher PJ (Oct 2001). "Identification of a new form of death-associated protein kinase that promotes cell survival". The Journal of Biological Chemistry 276 (43): 39667–78. doi:10.1074/jbc.M101886200. PMC 2823794. PMID 11485996.
Shohat G, Spivak-Kroizman T, Cohen O, Bialik S, Shani G, Berrisi H, Eisenstein M, Kimchi A (Dec 2001). "The pro-apoptotic function of death-associated protein kinase is controlled by a unique inhibitory autophosphorylation-based mechanism". The Journal of Biological Chemistry 276 (50): 47460–7. doi:10.1074/jbc.M105133200. PMID 11579085.
Soria JC, Rodriguez M, Liu DD, Lee JJ, Hong WK, Mao L (Jan 2002). "Aberrant promoter methylation of multiple genes in bronchial brush samples from former cigarette smokers". Cancer Research 62 (2): 351–5. PMID 11809677.
Larramendy ML, Niini T, Elonen E, Nagy B, Ollila J, Vihinen M, Knuutila S (Jun 2002). "Overexpression of translocation-associated fusion genes of FGFRI, MYC, NPMI, and DEK, but absence of the translocations in acute myeloid leukemia. A microarray analysis". Haematologica 87 (6): 569–77. PMID 12031912.
Hasegawa M, Nelson HH, Peters E, Ringstrom E, Posner M, Kelsey KT (Jun 2002). "Patterns of gene promoter methylation in squamous cell cancer of the head and neck". Oncogene 21 (27): 4231–6. doi:10.1038/sj.onc.1205528. PMID 12082610.
Jin Y, Blue EK, Dixon S, Shao Z, Gallagher PJ (Dec 2002). "A death-associated protein kinase (DAPK)-interacting protein, DIP-1, is an E3 ubiquitin ligase that promotes tumor necrosis factor-induced apoptosis and regulates the cellular levels of DAPK". The Journal of Biological Chemistry 277 (49): 46980–6. doi:10.1074/jbc.M208585200. PMC 2824503. PMID 12351649.
Wang WJ, Kuo JC, Yao CC, Chen RH (Oct 2002). "DAP-kinase induces apoptosis by suppressing integrin activity and disrupting matrix survival signals". The Journal of Cell Biology 159 (1): 169–79. doi:10.1083/jcb.200204050. PMC 2173490. PMID 12370243.
Nakatsuka S, Takakuwa T, Tomita Y, Hoshida Y, Nishiu M, Yamaguchi M, Nishii K, Yang WI, Aozasa K (Jan 2003). "Hypermethylation of death-associated protein (DAP) kinase CpG island is frequent not only in B-cell but also in T- and natural killer (NK)/T-cell malignancies". Cancer Science 94 (1): 87–91. doi:10.1111/j.1349-7006.2003.tb01357.x. PMID 12708480.
Tian JH, Das S, Sheng ZH (Jul 2003). "Ca2+-dependent phosphorylation of syntaxin-1A by the death-associated protein (DAP) kinase regulates its interaction with Munc18". The Journal of Biological Chemistry 278 (28): 26265–74. doi:10.1074/jbc.M300492200. PMID 12730201.
Gonzalez-Gomez P, Bello MJ, Alonso ME, Lomas J, Arjona D, Amiñoso C, De Campos JM, Isla A, Gutierrez M, Rey JA (2004). "Frequent death-associated protein-kinase promoter hypermethylation in brain metastases of solid tumors". Oncology Reports 10 (4): 1031–3. doi:10.3892/or.10.4.1031. PMID 12792765.
Matsumoto H, Nagao M, Ogawa S, Kanehiro H, Hisanaga M, Ko S, Ikeda N, Fujii H, Koyama F, Mukogawa T, Nakajima Y (2003). "Prognostic significance of death-associated protein-kinase expression in hepatocellular carcinomas". Anticancer Research 23 (2B): 1333–41. PMID 12820391.
Henshall DC, Araki T, Schindler CK, Shinoda S, Lan JQ, Simon RP (Sep 2003). "Expression of death-associated protein kinase and recruitment to the tumor necrosis factor signaling pathway following brief seizures". Journal of Neurochemistry 86 (5): 1260–70. doi:10.1046/j.1471-4159.2003.01934.x. PMID 12911633.
Voso MT, Scardocci A, Guidi F, Zini G, Di Mario A, Pagano L, Hohaus S, Leone G (Jan 2004). "Aberrant methylation of DAP-kinase in therapy-related acute myeloid leukemia and myelodysplastic syndromes". Blood 103 (2): 698–700. doi:10.1182/blood-2003-07-2249. PMID 14504087.
Jin Y, Gallagher PJ (Dec 2003). "Antisense depletion of death-associated protein kinase promotes apoptosis". The Journal of Biological Chemistry 278 (51): 51587–93. doi:10.1074/jbc.M309165200. PMC 2823796. PMID 14530257.
Kim WS, Son HJ, Park JO, Song SY, Park C (Dec 2003). "Promoter methylation and down-regulation of DAPK is associated with gastric atrophy". International Journal of Molecular Medicine 12 (6): 827–30. doi:10.3892/ijmm.12.6.827. PMID 14612952.
Bai T, Tanaka T, Yukawa K, Maeda M, Umesaki N (Mar 2004). "Reduced expression of death-associated protein kinase in human uterine and ovarian carcinoma cells". Oncology Reports 11 (3): 661–5. doi:10.3892/or.11.3.661. PMID 14767518.

PDB gallery

1ig1: 1.8A X-Ray structure of ternary complex of a catalytic domain of death-associated protein kinase with ATP analogue and Mn.

1jkk: 2.4A X-RAY STRUCTURE OF TERNARY COMPLEX OF A CATALYTIC DOMAIN OF DEATH-ASSOCIATED PROTEIN KINASE WITH ATP ANALOGUE AND MG.

1jkl: 1.6A X-RAY STRUCTURE OF BINARY COMPLEX OF A CATALYTIC DOMAIN OF DEATH-ASSOCIATED PROTEIN KINASE WITH ATP ANALOGUE

1jks: 1.5A X-RAY STRUCTURE OF APO FORM OF A CATALYTIC DOMAIN OF DEATH-ASSOCIATED PROTEIN KINASE

1jkt: TETRAGONAL CRYSTAL FORM OF A CATALYTIC DOMAIN OF DEATH-ASSOCIATED PROTEIN KINASE

1p4f: DEATH ASSOCIATED PROTEIN KINASE CATALYTIC DOMAIN WITH BOUND INHIBITOR FRAGMENT

1wvw: Crystal structures of kinase domain of DAP kinase in complex with small molecular inhibitors

1wvx: Crystal structures of kinase domain of DAP kinase in complex with small molecular inhibitors

1wvy: Crystal structures of kinase domain of DAP kinase in complex with small molecular inhibitors

Kinases: Serine/threonine-specific protein kinases (EC 2.7.11-12)

Serine/threonine-specific protein kinases (EC 2.7.11.1-EC 2.7.11.20)

Non-specific serine/threonine protein kinases (EC 2.7.11.1)	LATS1 LATS2 MAST1 MAST2 STK38 STK38L CIT ROCK1 SGK SGK2 SGK3 Protein kinase B AKT1 AKT2 AKT3 Ataxia telangiectasia mutated Mammalian target of rapamycin EIF-2 kinases PKR HRI EIF2AK3 EIF2AK4 Wee1 WEE1

Pyruvate dehydrogenase kinase (EC 2.7.11.2)	PDK1 PDK2 PDK3

Dephospho-(reductase kinase) kinase (EC 2.7.11.3)	AMP-activated protein kinase α PRKAA1 PRKAA2 β PRKAB1 PRKAB2 γ PRKAG1 PRKAG2 PRKAG3

(3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring)) (EC 2.7.11.4)	BCKDK BCKDHA BCKDHB

(isocitrate dehydrogenase (NADP+)) kinase (EC 2.7.11.5)	IDH2 IDH3A IDH3B IDH3G

(tyrosine 3-monooxygenase) kinase (EC 2.7.11.6)	STK4

Myosin-heavy-chain kinase (EC 2.7.11.7)	Aurora kinase Aurora A kinase Aurora B kinase

Fas-activated serine/threonine kinase (EC 2.7.11.8)	FASTK STK10

Goodpasture-antigen-binding protein kinase (EC 2.7.11.9)	-

IκB kinase (EC 2.7.11.10)	CHUK IKK2 TBK1 IKBKE IKBKG IKBKAP

cAMP-dependent protein kinase (EC 2.7.11.11)	Protein kinase A PRKACG PRKACB PRKACA PRKY

cGMP-dependent protein kinase (EC 2.7.11.12)	Protein kinase G PRKG1

Protein kinase C (EC 2.7.11.13)	Protein kinase C Protein kinase Cζ PKC alpha PRKCB1 PRKCD PRKCE PRKCH PRKCG PRKCI PRKCQ Protein kinase N1 PKN2 PKN3

Rhodopsin kinase (EC 2.7.11.14)	Rhodopsin kinase

Beta adrenergic receptor kinase (EC 2.7.11.15)	Beta adrenergic receptor kinase Beta adrenergic receptor kinase-2

G-protein coupled receptor kinases (EC 2.7.11.16)	GRK4 GRK5 GRK6

Ca2+/calmodulin-dependent (EC 2.7.11.17)	BRSK2 CAMK1 CAMK2A CAMK2B CAMK2D CAMK2G CAMK4 MLCK CASK CHEK1 CHEK2 DAPK1 DAPK2 DAPK3 STK11 MAPKAPK2 MAPKAPK3 MAPKAPK5 MARK1 MARK2 MARK3 MARK4 MELK MKNK1 MKNK2 NUAK1 NUAK2 OBSCN PASK PHKG1 PHKG2 PIM1 PIM2 PKD1 PRKD2 PRKD3 PSKH1 SNF1LK2 KIAA0999 STK40 SNF1LK SNRK SPEG TSSK2 Kalirin TRIB1 TRIB2 TRIB3 TRIO Titin DCLK1

Myosin light-chain kinase (EC 2.7.11.18)	MYLK MYLK2 MYLK3 MYLK4

Phosphorylase kinase (EC 2.7.11.19)	PHKA1 PHKA2 PHKB PHKG1 PHKG2

Elongation factor 2 kinase (EC 2.7.11.20)	EEF2K STK19

Polo kinase (EC 2.7.11.21)	PLK1 PLK2 PLK3 PLK4

Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30)

Polo kinase (EC 2.7.11.21)	PLK1 PLK2 PLK3 PLK4

Cyclin-dependent kinase (EC 2.7.11.22)	CDK1 CDK2 CDKL2 CDK3 CDK4 CDK5 CDKL5 CDK6 CDK7 CDK8 CDK9 CDK10 CDK12 CDC2L5 PCTK1 PCTK2 PCTK3 PFTK1 CDC2L1

(RNA-polymerase)-subunit kinase (EC 2.7.11.23)	RPS6KA5 RPS6KA4 P70S6 kinase P70-S6 Kinase 1 RPS6KB2 RPS6KA2 RPS6KA3 RPS6KA1 RPS6KC1

Mitogen-activated protein kinase (EC 2.7.11.24)	Extracellular signal-regulated MAPK1 MAPK3 MAPK4 MAPK6 MAPK7 MAPK12 MAPK15 C-Jun N-terminal MAPK8 MAPK9 MAPK10 P38 mitogen-activated protein MAPK11 MAPK13 MAPK14

MAP3K (EC 2.7.11.25)	MAP kinase kinase kinases MAP3K1 MAP3K2 MAP3K3 MAP3K4 MAP3K5 MAP3K6 MAP3K7 MAP3K8 RAFs ARAF BRAF KSR1 KSR2 MLKs MAP3K12 MAP3K13 MAP3K9 MAP3K10 MAP3K11 MAP3K7 ZAK CDC7 MAP3K14

Tau-protein kinase (EC 2.7.11.26)	TPK1 TTK GSK-3

(acetyl-CoA carboxylase) kinase (EC 2.7.11.27)	-

Tropomyosin kinase (EC 2.7.11.28)	-

Low-density-lipoprotein receptor kinase (EC 2.7.11.29)	-

Receptor protein serine/threonine kinase (EC 2.7.11.30)	Bone morphogenetic protein receptors BMPR1 BMPR1A BMPR1B BMPR2 ACVR1 ACVR1B ACVR1C ACVR2A ACVR2B ACVRL1 Anti-Müllerian hormone receptor

Dual-specificity kinases (EC 2.7.12)

MAP2K	MAP2K1 MAP2K2 MAP2K3 MAP2K4 MAP2K5 MAP2K6 MAP2K7

Proteins: enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis Enzyme kinetics Lineweaver–Burk plot Michaelis–Menten kinetics

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Types	EC1 Oxidoreductases(list) EC2 Transferases(list) EC3 Hydrolases(list) EC4 Lyases(list) EC5 Isomerases(list) EC6 Ligases(list)

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DAPK1

Function

As a drug target

References

Further reading