DAPK1

DAPK1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1IG1, 1JKK, 1JKL, 1JKS, 1JKT, 1P4F, 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, 4TL0, 4TXC, 4UV0, 4YO4, 4YPD, 5AUW, 5AUU, 5AV1, 5AUY, 5AUT, 5AUX, 5AUV, 5AUZ, 5AV0, 5AV4, 5AV2, 5AV3
Identifiers
Aliases	DAPK1, DAPK, death associated protein kinase 1, ROCO3
External IDs	OMIM: 600831; MGI: 1916885; HomoloGene: 3626; GeneCards: DAPK1; OMA:DAPK1 - orthologs
Gene location (Human)
Chr.	Chromosome 9 (human)
End	87,708,634 bp
Gene location (Mouse)
Chr.	Chromosome 13 (mouse)
End	60,911,005 bp
RNA expression pattern
	Top expressed in
	germinal epithelium; ; palpebral conjunctiva; ; placenta; ; left ovary; ; middle temporal gyrus; ; parietal pleura; ; corpus epididymis; ; gallbladder; ; pancreatic ductal cell; ; monocyte;
	Top expressed in
	saccule; ; lateral septal nucleus; ; otic vesicle; ; left lung lobe; ; olfactory tubercle; ; subiculum; ; genital tubercle; ; piriform cortex; ; pineal gland; ; anterior amygdaloid area;
	More reference expression data
	; ;
	More reference expression data
Gene ontology
Molecular function	transferase activity; nucleotide binding; GTP binding; syntaxin-1 binding; kinase activity; protein binding; identical protein binding; calmodulin-dependent protein kinase activity; protein serine/threonine kinase activity; calmodulin binding; ATP binding; protein kinase activity;
Cellular component	plasma membrane; actin cytoskeleton; cytoskeleton; cytoplasm; nucleus;
Biological process	regulation of apoptotic process; negative regulation of translation; phosphorylation; negative regulation of apoptotic process; positive regulation of cysteine-type endopeptidase activity involved in apoptotic process; regulation of autophagy; negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; apoptotic signaling pathway; protein autophosphorylation; regulation of translation; extrinsic apoptotic signaling pathway via death domain receptors; signal transduction; apoptotic process; regulation of NMDA receptor activity; protein phosphorylation; positive regulation of autophagy; intracellular signal transduction; cellular response to interferon-gamma; cellular response to hydroperoxide;
	Sources:Amigo / QuickGO
Orthologs
	1612
	69635
	ENSG00000196730
	ENSMUSG00000021559
	P53355
	Q80YE7
	NM_001288729; NM_001288730; NM_001288731; NM_004938
	NM_001285917; NM_029653; NM_134062
	NP_001275658; NP_001275659; NP_001275660; NP_004929
	NP_001272846; NP_083929; NP_598823
	Wikidata
View/Edit Human	View/Edit Mouse

Death-associated protein kinase 1 is an enzyme that in humans is encoded by the DAPK1 gene.^[5]

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.^[6]

In melanocytic cells DAPK1 gene expression may be regulated by MITF.^[7]

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.^[8] This has not been demonstrated in actual patients.

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000196730 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000021559 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ 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. S2CID 24698373.
^ 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. PMC 4563671. 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. S2CID 24566542.
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. PMC 11160098. PMID 12708480. S2CID 11818957.
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. S2CID 21971958.
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.

This article on a gene on human chromosome 9 is a stub. You can help Wikipedia by expanding it.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000196730 – Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000021559 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid8530096-5] 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-6] "Entrez Gene: DAPK1 death-associated protein kinase 1".

[pmid19067971-7] 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. S2CID 24698373.

[TNBCarticle-8] 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. PMC 4563671. PMID 26075823.

[1]

[2]

[3]

[4]

[5]

[6]

[7]

[8]

v t e Enzymes
Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis
Regulation	Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator
Classification	EC number Enzyme superfamily Enzyme family List of enzymes
Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics
Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

DAPK1

Function

As a drug target

References

Further reading

€4.95