InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: DAPK1

Summary

InnateDB Protein

IDBP-293165.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

DAPK1

Protein Name

death-associated protein kinase 1

Synonyms

DAPK;

Species

Homo sapiens

Ensembl Protein

ENSP00000386135

InnateDB Gene

IDBG-74918 (DAPK1)

Protein Structure

UniProt Annotation

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.Isoform 2 cannot induce apoptosis but can induce membrane blebbing.

Subcellular Localization

Isoform 1: Cytoplasm. Cytoplasm, cytoskeleton. Note=Colocalizes with MAP1B in the microtubules and cortical actin fibers.Isoform 2: Cytoplasm. Cytoplasm, cytoskeleton.

Disease Associations

Tissue Specificity

Isoform 2 is expressed in normal intestinal tissue as well as in colorectal carcinomas. {ECO:0000269PubMed:18422656}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 51 experimentally validated interaction(s) in this database.
They are also associated with 4 interaction(s) predicted by orthology.

Experimentally validated
Total	51 [view]
Protein-Protein	46 [view]
Protein-DNA	3 [view]
Protein-RNA	0
DNA-DNA	2 [view]
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	4 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003824	catalytic activity
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004683	calmodulin-dependent protein kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005516	calmodulin binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0016773	phosphotransferase activity, alcohol group as acceptor
GO:0042802	identical protein binding

Biological Process

GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0007165	signal transduction
GO:0008625	extrinsic apoptotic signaling pathway via death domain receptors
GO:0009103	lipopolysaccharide biosynthetic process
GO:0010506	regulation of autophagy
GO:0017148	negative regulation of translation
GO:0035556	intracellular signal transduction
GO:0042981	regulation of apoptotic process
GO:0043065	positive regulation of apoptotic process
GO:0043066	negative regulation of apoptotic process
GO:0046777	protein autophosphorylation
GO:0071346	cellular response to interferon-gamma
GO:0097190	apoptotic signaling pathway
GO:1902042	negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
GO:2000310	regulation of N-methyl-D-aspartate selective glutamate receptor activity

Cellular Component

GO:0005737	cytoplasm
GO:0015629	actin cytoskeleton
GO:0016020	membrane

Protein Structure and Domains

PDB ID

InterPro

IPR000488 Death domain
IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002110 Ankyrin repeat
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR010440 Lipopolysaccharide kinase
IPR011009 Protein kinase-like domain
IPR011029 Death-like domain
IPR018934 RIO-like kinase
IPR020635 Tyrosine-protein kinase, catalytic domain
IPR020683 Ankyrin repeat-containing domain
IPR027417 P-loop containing nucleoside triphosphate hydrolase

PFAM