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

Identifiers

Symbols

DAPK1 ; DAPK

External IDs

OMIM: 600831 MGI: 1916885 HomoloGene: 3626 IUPHAR: 2002 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 • identical protein binding
Cellular component	• cytoplasm • actin cytoskeleton
Biological process	• protein phosphorylation • apoptotic process • extrinsic apoptotic signaling pathway via death domain receptors • regulation of autophagy • negative regulation of translation • intracellular signal transduction • regulation of apoptotic process • positive regulation of apoptotic process • negative regulation of apoptotic process • protein autophosphorylation • cellular response to interferon-gamma • apoptotic signaling pathway • 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:
90.11 – 90.32 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]

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]

References

↑ Feinstein E, Druck T, Kastury K, Berissi H, Goodart SA, Overhauser J, Kimchi A, Huebner K (Feb 1996). "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 et al. (2008). "Novel MITF targets identified using a two-step DNA microarray strategy". Pigment Cell Melanoma Res. 21 (6): 665–76. doi:10.1111/j.1755-148X.2008.00505.x. PMID 19067971.

Deiss LP, Feinstein E, Berissi H et al. (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 Dev. 9 (1): 15–30. doi:10.1101/gad.9.1.15. PMID 7828849.
Inbal B, Shani G, Cohen O et al. (2000). "Death-associated protein kinase-related protein 1, a novel serine/threonine kinase involved in apoptosis.". Mol. Cell. Biol. 20 (3): 1044–54. doi:10.1128/MCB.20.3.1044-1054.2000. PMC 85221. PMID 10629061.
Jin Y, Blue EK, Dixon S et al. (2001). "Identification of a new form of death-associated protein kinase that promotes cell survival.". J. Biol. Chem. 276 (43): 39667–78. doi:10.1074/jbc.M101886200. PMC 2823794. PMID 11485996.
Shohat G, Spivak-Kroizman T, Cohen O et al. (2002). "The pro-apoptotic function of death-associated protein kinase is controlled by a unique inhibitory autophosphorylation-based mechanism.". J. Biol. Chem. 276 (50): 47460–7. doi:10.1074/jbc.M105133200. PMID 11579085.
Soria JC, Rodriguez M, Liu DD et al. (2002). "Aberrant promoter methylation of multiple genes in bronchial brush samples from former cigarette smokers.". Cancer Res. 62 (2): 351–5. PMID 11809677.
Larramendy ML, Niini T, Elonen E et al. (2003). "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 et al. (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 et al. (2003). "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.". J. Biol. Chem. 277 (49): 46980–6. doi:10.1074/jbc.M208585200. PMC 2824503. PMID 12351649.
Wang WJ, Kuo JC, Yao CC, Chen RH (2002). "DAP-kinase induces apoptosis by suppressing integrin activity and disrupting matrix survival signals.". J. Cell Biol. 159 (1): 169–79. doi:10.1083/jcb.200204050. PMC 2173490. PMID 12370243.
Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Nakatsuka S, Takakuwa T, Tomita Y et al. (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 Sci. 94 (1): 87–91. doi:10.1111/j.1349-7006.2003.tb01357.x. PMID 12708480.
Tian JH, Das S, Sheng ZH (2003). "Ca2+-dependent phosphorylation of syntaxin-1A by the death-associated protein (DAP) kinase regulates its interaction with Munc18.". J. Biol. Chem. 278 (28): 26265–74. doi:10.1074/jbc.M300492200. PMID 12730201.
Gonzalez-Gomez P, Bello MJ, Alonso ME et al. (2004). "Frequent death-associated protein-kinase promoter hypermethylation in brain metastases of solid tumors.". Oncol. Rep. 10 (4): 1031–3. doi:10.3892/or.10.4.1031. PMID 12792765.
Matsumoto H, Nagao M, Ogawa S et al. (2003). "Prognostic significance of death-associated protein-kinase expression in hepatocellular carcinomas.". Anticancer Res. 23 (2B): 1333–41. PMID 12820391.
Henshall DC, Araki T, Schindler CK et al. (2003). "Expression of death-associated protein kinase and recruitment to the tumor necrosis factor signaling pathway following brief seizures.". J. Neurochem. 86 (5): 1260–70. doi:10.1046/j.1471-4159.2003.01934.x. PMID 12911633.
Voso MT, Scardocci A, Guidi F et al. (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 (2004). "Antisense depletion of death-associated protein kinase promotes apoptosis.". J. Biol. Chem. 278 (51): 51587–93. doi:10.1074/jbc.M309165200. PMC 2823796. PMID 14530257.
Kim WS, Son HJ, Park JO et al. (2004). "Promoter methylation and down-regulation of DAPK is associated with gastric atrophy.". Int. J. Mol. Med. 12 (6): 827–30. doi:10.3892/ijmm.12.6.827. PMID 14612952.
Bai T, Tanaka T, Yukawa K et al. (2004). "Reduced expression of death-associated protein kinase in human uterine and ovarian carcinoma cells.". Oncol. Rep. 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 CDC2L5 CRKRS 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

Biochemistry overview
Enzymes overview
By EC number: 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
2.1
- 2
- 3
- 4
- 5
- 6
- 7
  - 2.7.10
  - 11-12
- 8
3.1
- - 3.1.3.48
- 2
- 3
- 4
  - 3.4.21
  - 22
  - 23
  - 24
- 5
- 6
- 7
4.1
- 2
- 3
- 4
- 5
- 6
5.1
- 2
- 3
- 4
- 99
6.1-3
- 4
- 5-6

DAPK1

References

Further reading