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DAPK3 Serine/threonine kinase which is involved in the regulation of apoptosis, autophagy, transcription, actin cytoskeleton reorganization, cell motility, smooth muscle contraction, and mitosis, particularly cytokinesis. 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. Regulates myosin phosphorylation in both smooth muscle and non- muscle cells. In smooth muscle, regulates myosin either directly by phosphorylating MYL12B and MYL9 or through inhibition of smooth muscle myosin phosphatase (SMPP1M) via phosphorylation of PPP1R12A, and the inhibition of SMPP1M functions to enhance muscle responsiveness to Ca(2+) and promote a contractile state. Enhances transcription from AR-responsive promoters in a hormone- and kinase-dependent manner. Phosphorylates STAT3 and enhances its transcriptional activity. Positively regulates the canonical Wnt/beta-catenin signaling through interaction with NLK and TCF7L2. Can disrupt the NLK-TCF7L2 complex thereby influencing the phosphorylation of TCF7L2 by NLK. Phosphorylates histone H3 on 'Thr-11' at centromeres during mitosis. Involved in the formation of promyelocytic leukemia protein nuclear body (PML-NB), one of many subnuclear domains in the eukaryotic cell nucleus, and which is involved in oncogenesis and viral infection. Monomer and homotrimer. Can also exist as homodimer or form heterodimers with ATF4. Homodimerization is required for activation segment autophosphorylation Both interactions require an intact leucine zipper domain and oligomerization is required for full enzymatic activity. Also binds to DAXX and PAWR, possibly in a ternary complex which plays a role in caspase activation. According to PubMed:17953487, does not interact with PARW. Interacts with AATF, CDC5L, UBE2D1, UBE2D2 AND UBE2D3. Interacts with AR and this interaction is enhanced by AATF. Interacts (via leucine zipper) with TCP10L (via leucine zipper). Interacts (via kinase domain) with DAPK1 (via kinase domain).Interacts with STAT3, NLK and TCF7L2. Isoform 1 and isoform 2 can interact with myosin and PPP1R12A. Isoform 2 is expressed in the bladder smooth muscle. Inhibited by pyridone 6 (K00225), a potent, ATP-competitive inhibitor. Phosphorylation at Thr-180, Thr-225 and Thr-265 is essential for activity. Oligomerization is required for full enzymatic activity. Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. DAP kinase subfamily. 2 isoforms of the human protein are produced by alternative splicing. Note: This description may include information from UniProtKB.
Protein type: CAMK group; DAPK family; EC; Kinase, protein; Protein kinase, CAMK; Protein kinase, Ser/Thr (non-receptor); Tumor suppressor
Chromosomal Location of Human Ortholog: 19p13.3
Cellular Component: actin filament; cytoplasm; membrane raft; nucleus; PML body
Molecular Function: ATP binding; cAMP response element binding protein binding; identical protein binding; leucine zipper domain binding; protein binding; protein C-terminus binding; protein homodimerization activity; protein serine/threonine kinase activity; Rho GTPase binding
Biological Process: apoptosis; cellular response to interferon-gamma; covalent chromatin modification; negative regulation of translation; neuron differentiation; peptidyl-serine phosphorylation; peptidyl-threonine phosphorylation; positive regulation of apoptosis; positive regulation of canonical Wnt signaling pathway; positive regulation of cell migration; positive regulation of extrinsic apoptotic signaling pathway in absence of ligand; protein amino acid phosphorylation; protein autophosphorylation; regulation of actin cytoskeleton reorganization; regulation of apoptosis; regulation of autophagy; regulation of cell motility; regulation of cell shape; regulation of focal adhesion formation; regulation of mitotic cell cycle; regulation of mitotic nuclear division; regulation of myosin II filament organization; regulation of smooth muscle contraction; regulation of transcription, DNA-templated; transcription, DNA-dependent
Reference #:  O43293 (UniProtKB)
Alt. Names/Synonyms: DAP kinase 3; DAP-like kinase; DAPK3; Death-associated protein kinase 3; Dlk; FLJ36473; ZIP; ZIP kinase isoform; ZIP-kinase; ZIPK
Gene Symbols: DAPK3
Molecular weight: 52,536 Da
Basal Isoelectric point: 6.44  Predict pI for various phosphorylation states
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