InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: DAPK3

Summary

InnateDB Protein

IDBP-18097.6

Last Modified

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

Gene Symbol

DAPK3

Protein Name

death-associated protein kinase 3

Synonyms

DLK; ZIP; ZIPK;

Species

Homo sapiens

Ensembl Protein

ENSP00000301264

InnateDB Gene

IDBG-18095 (DAPK3)

Protein Structure

UniProt Annotation

Function

Serine/threonine kinase which is involved in the regulation of apoptosis, autophagy, transcription, translation, 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. Phosphorylates RPL13A on 'Ser-77' upon interferon-gamma activation which is causing RPL13A release from the ribosome, its association with the GAIT complex and its subsequent involvement in transcript- selective translation inhibition.Isoform 2 can phosphorylate myosin, PPP1R12A and MYL12B.

Subcellular Localization

Nucleus. Cytoplasm. Nucleus, PML body. Chromosome, centromere. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome. Note=The phosphorylated form is anchored in the cytoplasm and/or prevented from being shuttled to the nucleus, whereas nuclear translocation or retention is maximal when it is not phosphorylated. Phosphorylation at Thr-299 promotes cytoplasmic localization. Relocates to the cytoplasm on binding PAWR where the complex appears to interact with actin filaments. Localizes to promyelocytic leukemia protein nuclear bodies (PML- NBs). Associated: with the centrosomes throughout the mitotic cell cycle, with the centromeres from prophase to anaphase and with the contractile ring during cytokinesis.Isoform 2: Nucleus. Cytoplasm.

Disease Associations

Tissue Specificity

Isoform 2 is expressed in the bladder smooth muscle. {ECO:0000269PubMed:17126281}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 31 experimentally validated interaction(s) in this database.
They are also associated with 5 interaction(s) predicted by orthology.

Experimentally validated
Total	31 [view]
Protein-Protein	31 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	5 [view]

Gene Ontology

Molecular Function

Accession	GO Term
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:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0016773	phosphotransferase activity, alcohol group as acceptor
GO:0042802	identical protein binding
GO:0042803	protein homodimerization activity
GO:0043522	leucine zipper domain binding

Biological Process

GO:0000910	cytokinesis
GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0006468	protein phosphorylation
GO:0006915	apoptotic process
GO:0006940	regulation of smooth muscle contraction
GO:0007088	regulation of mitosis
GO:0009103	lipopolysaccharide biosynthetic process
GO:0010506	regulation of autophagy
GO:0016568	chromatin modification
GO:0017148	negative regulation of translation
GO:0035556	intracellular signal transduction
GO:0042981	regulation of apoptotic process
GO:0046777	protein autophosphorylation
GO:0071346	cellular response to interferon-gamma
GO:0090263	positive regulation of canonical Wnt signaling pathway
GO:2000145	regulation of cell motility
GO:2000249	regulation of actin cytoskeleton reorganization

Cellular Component

GO:0000775	chromosome, centromeric region
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005815	microtubule organizing center
GO:0016020	membrane
GO:0016605	PML body

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR010440 Lipopolysaccharide kinase
IPR011009 Protein kinase-like domain
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714
PF06293

PRINTS

PR00109

PIRSF

SMART

SM00220
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt