======= DAPK1 ======= == Gene Information == * **Official Symbol**: DAPK1 * **Official Name**: death associated protein kinase 1 * **Aliases and Previous Symbols**: N/A * **Entrez ID**: [[https://www.ncbi.nlm.nih.gov/gene/?term=1612|1612]] * **UniProt**: [[https://www.uniprot.org/uniprot/P53355|P53355]] * **Interactions**: [[https://thebiogrid.org/search.php?search=DAPK1&organism=9606|BioGRID]] * **PubMed articles**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20DAPK1|Open PubMed]] * **OMIM**: [[https://omim.org/entry/600831|Open OMIM]] == Function Summary == * **Entrez Summary**: 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. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]. * **UniProt Summary**: Calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that trigger cell survival, apoptosis, and autophagy. Regulates both type I apoptotic and type II autophagic cell deaths signal, depending on the cellular setting. The former is caspase-dependent, while the latter is caspase-independent and is characterized by the accumulation of autophagic vesicles. Phosphorylates PIN1 resulting in inhibition of its catalytic activity, nuclear localization, and cellular function. Phosphorylates TPM1, enhancing stress fiber formation in endothelial cells. Phosphorylates STX1A and significantly decreases its binding to STXBP1. Phosphorylates PRKD1 and regulates JNK signaling by binding and activating PRKD1 under oxidative stress. Phosphorylates BECN1, reducing its interaction with BCL2 and BCL2L1 and promoting the induction of autophagy. Phosphorylates TSC2, disrupting the TSC1-TSC2 complex and stimulating mTORC1 activity in a growth factor-dependent pathway. Phosphorylates RPS6, MYL9 and DAPK3. Acts as a signaling amplifier of NMDA receptors at extrasynaptic sites for mediating brain damage in stroke. Cerebral ischemia recruits DAPK1 into the NMDA receptor complex and it phosphorylates GRINB at Ser-1303 inducing injurious Ca(2+) influx through NMDA receptor channels, resulting in an irreversible neuronal death. Required together with DAPK3 for phosphorylation of RPL13A upon interferon-gamma activation which is causing RPL13A involvement in transcript- selective translation inhibition. |Kdo| |Death| |Pkinase Tyr| |Ank 2| |Ank| |Pkinase| |cellular response to hydroperoxide| |response to hydroperoxide| |calmodulin-dependent protein kinase activity| |syntaxin-1 binding| |extrinsic apoptotic signaling pathway via death domain receptors| |regulation of NMDA receptor activity| |regulation of glutamate receptor signaling pathway| |regulation of neurotransmitter receptor activity| |extrinsic apoptotic signaling pathway| |positive regulation of autophagy| |negative regulation of translation| |positive regulation of cysteine-type endopeptidase activity involved in apoptotic process| |negative regulation of cellular amide metabolic process| |positive regulation of cysteine-type endopeptidase activity| |cellular response to interferon-gamma| |regulation of cation channel activity| |regulation of signaling receptor activity| |positive regulation of endopeptidase activity| |response to interferon-gamma| |positive regulation of peptidase activity| |protein autophosphorylation| |calmodulin binding| |regulation of cysteine-type endopeptidase activity involved in apoptotic process| |actin cytoskeleton| |protein kinase activity| |cellular response to oxidative stress| |regulation of cysteine-type endopeptidase activity| |regulation of ion transmembrane transporter activity| |regulation of transmembrane transporter activity| |regulation of transporter activity| |apoptotic signaling pathway| |regulation of autophagy| |regulation of cation transmembrane transport| |regulation of translation| |positive regulation of proteolysis| |protein serine/threonine kinase activity| |positive regulation of cellular catabolic process| |response to oxidative stress| |GTP binding| |regulation of cellular amide metabolic process| |regulation of endopeptidase activity| |positive regulation of catabolic process| |regulation of peptidase activity| |regulation of ion transmembrane transport| |posttranscriptional regulation of gene expression| |regulation of transmembrane transport| |positive regulation of apoptotic process| |positive regulation of programmed cell death| |positive regulation of cell death| |regulation of ion transport| |regulation of proteolysis| |innate immune response| |positive regulation of hydrolase activity| |regulation of cellular catabolic process| |negative regulation of apoptotic process| |negative regulation of programmed cell death| |apoptotic process| |defense response to other organism| |protein phosphorylation| |regulation of catabolic process| |negative regulation of cell death| |cellular response to cytokine stimulus| |negative regulation of cellular protein metabolic process| |programmed cell death| |cellular response to oxygen-containing compound| |identical protein binding| |cell death| |response to cytokine| |negative regulation of protein metabolic process| |regulation of hydrolase activity| |phosphorylation| |response to other organism| |response to external biotic stimulus| |response to biotic stimulus| |defense response| |negative regulation of cellular macromolecule biosynthetic process| |positive regulation of catalytic activity| |negative regulation of macromolecule biosynthetic process| |ATP binding| |negative regulation of cellular biosynthetic process| |regulation of apoptotic process| |negative regulation of biosynthetic process| |response to oxygen-containing compound| |regulation of programmed cell death| |positive regulation of cellular protein metabolic process| |regulation of cell death| |intracellular signal transduction| |cellular response to stress| |positive regulation of protein metabolic process| |negative regulation of gene expression| |positive regulation of molecular function| |regulation of transport| |immune response| \\ === CRISPR Data === ^Screen^Score^ |[[:results:exp65|Mubritinib 0.2μM R02 exp65]]|1.7| |[[:results:exp416|Tubacin 1.6μM R07 exp416]]|1.75| |[[:results:exp130|JQ1 0.01μM R03 exp130]]|1.81| |[[:results:exp227|Cryptotanshinone 12μM R05 exp227]]|2.02| |[[:results:exp140|Nicotinate 1000μM R03 exp140]]|2.09| No correlation found to any other genes in chemogenomics. Global Fraction of Cell Lines Where Essential: 0/739 ^Tissue^Fraction Of Cell Lines Where Essential^ |1290807.0|0/1| |909776.0|0/1| |bile duct|0/28| |blood|0/28| |bone|0/26| |breast|0/33| |central nervous system|0/56| |cervix|0/4| |colorectal|0/17| |esophagus|0/13| |fibroblast|0/1| |gastric|0/16| |kidney|0/21| |liver|0/20| |lung|0/75| |lymphocyte|0/16| |ovary|0/26| |pancreas|0/24| |peripheral nervous system|0/16| |plasma cell|0/15| |prostate|0/1| |skin|0/24| |soft tissue|0/9| |thyroid|0/2| |upper aerodigestive|0/22| |urinary tract|0/29| |uterus|0/5| == Essentiality in NALM6 == * **Essentiality Rank**: 12733 * **Expression level (log2 read counts)**: -2.79 {{:chemogenomics:nalm6 dist.png?nolink |}}