Death-associated protein kinase 1

UniProt P53355 Organism Homo sapiens Gene DAPK, DAPK1 EC 2.7.11.1

Also known as: DAPK, DAPK1

Function

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.

Classification

Family (Pfam): PF00023 Ank, PF12796 Ank_2, PF13637 Ank_4, PF00531 Death, PF00069 Pkinase
InterPro: Ankyrin_rpt, Ankyrin_rpt-contain_sf, DAPK1_cat, DEATH-like_dom_sf, Death_dom, Kinase-like_dom_sf, P-loop_NTPase, Prot_kinase_dom, Protein_kinase_ATP_BS, ROC, Ser/Thr_kinase_AS
Functional cluster: Serine/Threonine Protein Kinases

Experimental structures · PDB · 78

1IG1 X-ray 1.80A
1JKK X-ray 2.40A
1JKL X-ray 1.62A
1JKS X-ray 1.50A
1JKT X-ray 3.50A
1P4F X-ray 1.90A
1WVW X-ray 2.40A
1WVX X-ray 2.60A
1WVY X-ray 2.80A
1YR5 X-ray 1.70A
2W4J X-ray 1.30A
2W4K X-ray 1.90A
… and 66 more

A predicted model is available from AlphaFold.

Gene Ontology · 33

Neighborhood · nearest proteins

Nearest neighbours of Death-associated protein kinase 1: 3 by sequence/function similarity (left); 3 co-cited in the literature (right).

Related proteins · sequence + function similarity

Death-associated protein kinase 1 0.99
Death-associated protein kinase dapk-1 0.88
Death-associated protein kinase 2 0.68
Integrin-linked protein kinase homolog pat-4 0.68
Scaffold protein ILK 0.68
Scaffold protein ILK 0.67
Scaffold protein ILK 0.67
Ankyrin repeat and protein kinase domain-containing protein 1 0.67
Scaffold protein ILK 0.67
Scaffold protein ILK 0.67
Death-associated protein kinase 2 0.67
Scaffold protein ILK 0.67

Co-cited proteins · studied together in the literature

Death-associated protein kinase 2 4 shared papers
Death-associated protein 1 1 shared papers
Death-associated protein kinase 3 4 shared papers
Microtubule-associated protein 1B 1 shared papers
Tropomyosin alpha-1 chain 1 shared papers
Death-associated protein kinase 2 2 shared papers
Serine/threonine-protein kinase D1 1 shared papers
Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1 1 shared papers
Netrin-1 1 shared papers
Programmed cell death protein 6 1 shared papers
Netrin receptor UNC5C 1 shared papers
Large ribosomal subunit protein uL13 1 shared papers

Literature · 34 cited papers

An Alzheimer Disease-linked Rare Mutation Potentiates Netrin Receptor Uncoordinated-5C-induced Signaling That Merges with Amyloid beta Precursor Protein Signaling. J. Biol. Chem. · 2016
An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J. Proteomics · 2014
Toward a comprehensive characterization of a human cancer cell phosphoproteome. J. Proteome Res. · 2013
Death-associated protein kinase 1 phosphorylates Pin1 and inhibits its prolyl isomerase activity and cellular function. Mol. Cell · 2011
New modularity of DAP-kinases: alternative splicing of the DRP-1 gene produces a ZIPk-like isoform. PLoS ONE · 2011
System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci. Signal. · 2011
The Cullin 3 substrate adaptor KLHL20 mediates DAPK ubiquitination to control interferon responses. EMBO J. · 2010
Death-associated protein kinase (DAPK) and signal transduction: additional roles beyond cell death. FEBS J. · 2010
DAP-kinase-mediated phosphorylation on the BH3 domain of beclin 1 promotes dissociation of beclin 1 from Bcl-XL and induction of autophagy. EMBO Rep. · 2009
DAPK-ZIPK-L13a axis constitutes a negative-feedback module regulating inflammatory gene expression. Mol. Cell · 2008
Peptide combinatorial libraries identify TSC2 as a death-associated protein kinase (DAPK) death domain-binding protein and reveal a stimulatory role for DAPK in mTORC1 signaling. J. Biol. Chem. · 2009
An alternative transcript from the death-associated protein kinase 1 locus encoding a small protein selectively mediates membrane blebbing. FEBS J. · 2008
… and 22 more in the literature graph

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