DAPK1

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

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
Gene location (Human) Chr. Chromosome 9 (human)[1] Band 9q21.33 Start 87,497,228 bp[1] End 87,708,634 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13 B2|13 32.53 cM Start 60,601,947 bp[2] End 60,763,191 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • transferase activity • nucleotide binding • GTP binding • syntaxin-1 binding • kinase activity • GO:0001948 protein binding • identical protein binding • calmodulin-dependent protein kinase activity • protein serine/threonine kinase activity • calmodulin binding • ATP binding • protein kinase activity Cellular component • cell membrane • actin cytoskeleton • cytoskeleton • cytoplasm • cell 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 • 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 • GO:0007243 intracellular signal transduction • cellular response to interferon-gamma • cellular response to hydroperoxide Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	1612	69635
Ensembl	ENSG00000196730	ENSMUSG00000021559
UniProt	P53355	Q80YE7
RefSeq (mRNA)	NM_001288729 NM_001288730 NM_001288731 NM_004938	NM_001285917 NM_029653 NM_134062
RefSeq (protein)	NP_001275658 NP_001275659 NP_001275660 NP_004929	NP_001272846 NP_083929 NP_598823
Location (UCSC)	Chr 9: 87.5 – 87.71 Mb	Chr 13: 60.6 – 60.76 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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

1. GRCh38: Ensembl release 89: ENSG00000196730 - Ensembl, May 2017
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.
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.
6. "Entrez Gene: DAPK1 death-associated protein kinase 1".
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.
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.

Further reading

• 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. 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.