InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: VRK2

Summary

InnateDB Protein

IDBP-376751.5

Last Modified

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

Gene Symbol

VRK2

Protein Name

vaccinia related kinase 2

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000402375

InnateDB Gene

IDBG-52815 (VRK2)

Protein Structure

UniProt Annotation

Function

Serine/threonine kinase that regulates several signal transduction pathways. Isoform 1 modulates the stress response to hypoxia and cytokines, such as interleukin-1 beta (IL1B) and this is dependent on its interaction with MAPK8IP1, which assembles mitogen-activated protein kinase (MAPK) complexes. Inhibition of signal transmission mediated by the assembly of MAPK8IP1-MAPK complexes reduces JNK phosphorylation and JUN-dependent transcription. Phosphorylates 'Thr-18' of p53/TP53, histone H3, and may also phosphorylate MAPK8IP1. Phosphorylates BANF1 and disrupts its ability to bind DNA and reduces its binding to LEM domain-containing proteins. Downregulates the transactivation of transcription induced by ERBB2, HRAS, BRAF, and MEK1. Blocks the phosphorylation of ERK in response to ERBB2 and HRAS. Can also phosphorylate the following substrates that are commonly used to establish in vitro kinase activity: casein, MBP and histone H2B, but it is not sure that this is physiologically relevant.Isoform 2 phosphorylates 'Thr-18' of p53/TP53, as well as histone H3. Reduces p53/TP53 ubiquitination by MDM2, promotes p53/TP53 acetylation by EP300 and thereby increases p53/TP53 stability and activity.

Subcellular Localization

Isoform 1: Cytoplasm. Endoplasmic reticulum membrane {ECO:0000305}; Single-pass type IV membrane protein {ECO:0000305}. Mitochondrion membrane {ECO:0000305}; Single-pass type IV membrane protein {ECO:0000305}.Isoform 2: Cytoplasm. Nucleus.

Disease Associations

Tissue Specificity

Isoform 1 and isoform 2 are expressed in various tumor cell lines. Expression of isoform 1 inversely correlates with ERBB2 in breast carcinomas (at protein level). Widely expressed. Highly expressed in fetal liver, skeletal muscle, pancreas, heart, peripheral blood leukocytes and testis. {ECO:0000269PubMed:16704422, ECO:0000269PubMed:20679487, ECO:0000269PubMed:9344656}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 20 experimentally validated interaction(s) in this database.
They are also associated with 1 interaction(s) predicted by orthology.

Experimentally validated
Total	20 [view]
Protein-Protein	20 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	1 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0016772	transferase activity, transferring phosphorus-containing groups

Biological Process

GO:0006468	protein phosphorylation
GO:0016032	viral process
GO:0034599	cellular response to oxidative stress
GO:0043408	regulation of MAPK cascade
GO:0046777	protein autophosphorylation
GO:2000659	regulation of interleukin-1-mediated signaling pathway

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005783	endoplasmic reticulum
GO:0005789	endoplasmic reticulum membrane
GO:0016021	integral component of membrane
GO:0031966	mitochondrial membrane

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
IPR011009 Protein kinase-like domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

SMART

SM00220

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt