DAPK3
Description
The DAPK3 (death associated protein kinase 3) is a protein-coding gene located on chromosome 19.
Death-associated protein kinase 3 is an enzyme that in humans is encoded by the DAPK3 gene.
== Function == Death-associated protein kinase 3 (DAPK3) induces morphological changes in apoptosis when overexpressed in mammalian cells. These results suggest that DAPK3 may play a role in the induction of apoptosis. Unlike most other mammalian genes, murine (rat and mouse) DAPK3 has undergone accelerated evolution and diverged from the tightly conserved consensus that is maintained from fish to human.
== Interactions == DAPK3 has been shown to interact with PAWR and Death associated protein 6.
DAPK3 is a serine/threonine kinase involved in various cellular processes including apoptosis, autophagy, transcription, translation, and actin cytoskeleton reorganization. It plays a role in the regulation of smooth muscle contraction by directly phosphorylating MYL12B and MYL9 or by inhibiting smooth muscle myosin phosphatase (SMPP1M) via phosphorylation of PPP1R12A. This inhibition enhances muscle responsiveness to Ca(2+) and promotes contraction. In non-muscle cells, DAPK3 phosphorylates MYL12B, leading to actin cytoskeleton reorganization. Overexpression of DAPK3 results in condensation of actin stress fibers into thick bundles, indicating its involvement in actin filament focal adhesion dynamics. DAPK3 interacts with RhoD, which modulates its function in both actin cytoskeleton reorganization and focal adhesion dissolution. It positively regulates canonical Wnt/beta-catenin signaling through interaction with NLK and TCF7L2. Upon interferon-gamma activation, DAPK3 phosphorylates RPL13A on 'Ser-77', leading to its release from the ribosome, association with the GAIT complex, and subsequent involvement in transcript-selective translation inhibition. DAPK3 also enhances transcription from AR-responsive promoters in a hormone- and kinase-dependent manner. It is implicated in the regulation of cell cycle progression and cell proliferation, and may act as a tumor suppressor. DAPK3 exists as a homooligomer in its kinase-active form (homotrimers and homodimers) and as a monomer in its kinase-inactive form. Homodimerization is necessary for activation segment autophosphorylation. Isoform 1 and isoform 2 interact with myosin and PPP1R12A; the interaction of isoform 1 with PPP1R12A is inhibited by RhoA dominant negative form. DAPK3 also interacts with NLK, DAXX, STAT3, RHOD (GTP-bound form), TCP10L, PAWR, and ULK1. It may be a substrate of ULK1.
DAPK3 is also known as DLK, ZIP, ZIPK.
Associated Diseases
- low grade glioma
- esophageal cancer
- schizophrenia 15
- cryopyrin-associated periodic syndrome
- Phelan-McDermid syndrome
- intellectual disability, autosomal dominant 50
- Potocki-Lupski syndrome
- FRAXE intellectual disability
- intellectual developmental disorder, X-linked, syndromic, Pilorge type
- Smith-Magenis syndrome
- intellectual developmental disorder with epilepsy, behavioral abnormalities, and coarse facies
