DAPK1

Description

The DAPK1 (death associated protein kinase 1) is a protein-coding gene located on chromosome 9.

DAPK1 (Death-associated protein kinase 1) is an enzyme encoded by the DAPK1 gene in humans. It is a positive mediator of gamma-interferon induced programmed cell death. DAPK1 is a 160-kD calmodulin-dependent serine-threonine kinase that contains 8 ankyrin repeats and 2 putative P-loop consensus sites. It is considered a tumor suppressor candidate. In melanocytic cells, DAPK1 gene expression can be regulated by MITF. DAPK1 depletion can inhibit tumor cell growth in models of triple receptor-negative breast cancer with p53-mutant cancers, but this has not been demonstrated in actual patients.

DAPK1 is a calcium/calmodulin-dependent serine/threonine kinase involved in multiple cellular signaling pathways that regulate cell survival, apoptosis, and autophagy. It can trigger both type I apoptotic and type II autophagic cell death pathways, depending on the cellular context. Type I apoptosis is caspase-dependent, while type II autophagy is caspase-independent and characterized by the accumulation of autophagic vesicles. DAPK1 phosphorylates various proteins, influencing their function and contributing to its diverse roles. For example, it phosphorylates PIN1, inhibiting its catalytic activity, nuclear localization, and overall function. DAPK1 also phosphorylates TPM1, enhancing stress fiber formation in endothelial cells. It phosphorylates STX1A, decreasing its binding to STXBP1. DAPK1 further phosphorylates PRKD1, regulating JNK signaling by binding and activating PRKD1 under oxidative stress. It also phosphorylates BECN1, reducing its interaction with BCL2 and BCL2L1, promoting autophagy induction. DAPK1 can phosphorylate TSC2, disrupting the TSC1-TSC2 complex and stimulating mTORC1 activity in a growth factor-dependent pathway. It also phosphorylates RPS6, MYL9, and DAPK3. DAPK1 acts as a signaling amplifier of NMDA receptors at extrasynaptic sites, contributing to brain damage during stroke. Cerebral ischemia recruits DAPK1 into the NMDA receptor complex, where it phosphorylates GRINB at Ser-1303, inducing harmful Ca(2+) influx through NMDA receptor channels and causing irreversible neuronal death. DAPK1 is essential for phosphorylation of RPL13A, together with DAPK3, upon interferon-gamma activation. This phosphorylation leads to RPL13A involvement in transcript-selective translation inhibition.

DAPK1 is also known as DAPK, ROCO3.

Associated Diseases

WES Whole Exome Sequencing

Clinical Exome Sequencing