VRK2 VRK serine/threonine kinase 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: VRK2provided by HGNC
Official Full Name: VRK serine/threonine kinase 2provided by HGNC
Primary source: HGNC:HGNC:12719
See related: Ensembl:ENSG00000028116 MIM:602169; AllianceGenome:HGNC:12719
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary: This gene encodes a member of the vaccinia-related kinase (VRK) family of serine/threonine protein kinases. The encoded protein acts as an effector of signaling pathways that regulate apoptosis and tumor cell growth. Variants in this gene have been associated with schizophrenia. Alternative splicing results in multiple transcript variants that differ in their subcellular localization and biological activity. [provided by RefSeq, Jan 2014]
Expression: Ubiquitous expression in adrenal (RPKM 6.3), appendix (RPKM 5.7) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 2p16.1

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (57907592..58159920)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (57912292..58164754)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (58134727..58387055)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Elucidating the interaction of C-terminal domain of Vaccinia-Related Kinase 2A (VRK2A) with B-cell lymphoma-extra Large (Bcl-xL) to decipher its anti-apoptotic role in cancer.
Title: Elucidating the interaction of C-terminal domain of Vaccinia-Related Kinase 2A (VRK2A) with B-cell lymphoma-extra Large (Bcl-xL) to decipher its anti-apoptotic role in cancer.
Reduced Vrk2 expression is associated with higher risk of depression in humans and mediates depressive-like behaviors in mice.
Title: Reduced Vrk2 expression is associated with higher risk of depression in humans and mediates depressive-like behaviors in mice.
VRK1 as a synthetic lethal target in VRK2 promoter-methylated cancers of the nervous system.
Title: VRK1 as a synthetic lethal target in VRK2 promoter-methylated cancers of the nervous system.
VRK2 activates TNFalpha/NF-kappaB signaling by phosphorylating IKKbeta in pancreatic cancer.
Title: VRK2 activates TNFα/NF-κB signaling by phosphorylating IKKβ in pancreatic cancer.
Evaluation of the relationship between VRK2, rs4380187 polymorphisms, and genetic susceptibility to schizophrenia in the Chinese Han population.
Title: Evaluation of the relationship between VRK2, rs4380187 polymorphisms, and genetic susceptibility to schizophrenia in the Chinese Han population.
Vaccinia-related kinase 2 blunts sorafenib's efficacy against hepatocellular carcinoma by disturbing the apoptosis-autophagy balance.
Title: Vaccinia-related kinase 2 blunts sorafenib's efficacy against hepatocellular carcinoma by disturbing the apoptosis-autophagy balance.
our work reveals the regulation of dysbindin by VRK2, providing the association of these two proteins, which are commonly implicated in schizophrenia
Title: Vaccinia-related kinase 2 modulates role of dysbindin by regulating protein stability.
Structural characterization of human vaccinia-related kinases, VRK1 and VRK2, bound to small-molecule inhibitors, has been reported.
Title: Structural characterization of human Vaccinia-Related Kinases (VRK) bound to small-molecule inhibitors identifies different P-loop conformations.
a novel insight into the oncogenic activity of VRK2-Akt complexes in the lysosomes via modulation of autophagy
Title: Functional characterization of lysosomal interaction of Akt with VRK2.
VRK2 is suggested as a candidate gene for neurological disorders through its role in signaling pathway, the neuronal loss and stress response.
Title: Vaccinia Related Kinase 2 (VRK2) expression in neurological disorders: schizophrenia, epilepsy and multiple sclerosis.

Submit: New GeneRIF Correction See all GeneRIFs (35)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Biological insights from 108 schizophrenia-associated genetic loci. EBI GWAS Catalog EBI GWAS CatalogPubMed
Common variants conferring risk of schizophrenia. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genetic determinants of common epilepsies: a meta-analysis of genome-wide association studies. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Pr55(Gag)	gag	The amplified luminescent proximity homogeneous assay (AlphaScreen) identifies the interaction of HIV-1 Gag with VRK2	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-35879 (e-PCR)
- UniSTS:40461

RH66429 (e-PCR)
- UniSTS:44582

RH78793 (e-PCR)
- UniSTS:2746

VRK2 (e-PCR)
- UniSTS:279257

D2S2913 (e-PCR)
- UniSTS:238

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables histone H2AS1 kinase activity	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein domain specific binding	IDA Inferred from Direct Assay more info	PubMed
enables protein kinase binding	IDA Inferred from Direct Assay more info	PubMed
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA damage response	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to oxidative stress	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in chromatin remodeling	IEA Inferred from Electronic Annotation more info
involved_in protein autophosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein phosphorylation	TAS Traceable Author Statement more info	PubMed
involved_in regulation of MAPK cascade	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of interleukin-1-mediated signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in signal transduction	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum	IDA Inferred from Direct Assay more info	PubMed
located_in endoplasmic reticulum membrane	IDA Inferred from Direct Assay more info	PubMed
located_in mitochondrial membrane	IDA Inferred from Direct Assay more info	PubMed
located_in nuclear envelope	ISS Inferred from Sequence or Structural Similarity more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: serine/threonine-protein kinase VRK2

Names: vaccinia related kinase 2; vaccinia virus B1R-related kinase 2

NP_001123952.1

EC 2.7.11.1

NP_001123953.1

EC 2.7.11.1

NP_001123954.1

EC 2.7.11.1

NP_001123955.1

EC 2.7.11.1

NP_001275765.1

EC 2.7.11.1

NP_001275766.1

EC 2.7.11.1

NP_001275767.1

EC 2.7.11.1

NP_001275768.1

EC 2.7.11.1

NP_006287.2

EC 2.7.11.1

XP_005264597.1

EC 2.7.11.1

XP_006712153.1

EC 2.7.11.1

XP_006712154.1

EC 2.7.11.1

XP_011531394.1

EC 2.7.11.1

XP_047301701.1

EC 2.7.11.1

XP_047301703.1

EC 2.7.11.1

XP_047301704.1

EC 2.7.11.1

XP_054199726.1

EC 2.7.11.1

XP_054199727.1

EC 2.7.11.1

XP_054199728.1

EC 2.7.11.1

XP_054199729.1

EC 2.7.11.1

XP_054199730.1

EC 2.7.11.1

XP_054199731.1

EC 2.7.11.1

XP_054199732.1

EC 2.7.11.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_029717.2 RefSeqGene

Range

144066..257131

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001130480.2 → NP_001123952.1 serine/threonine-protein kinase VRK2 isoform 1

See identical proteins and their annotated locations for NP_001123952.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Variants 1, 2, 3, and 8 encode the same isoform (1, also known as VRK2A).

Source sequence(s)

AB000450, AK223540, AK311205, DB227029

Consensus CDS

CCDS1859.1

UniProtKB/Swiss-Prot

B4DKL0, D6W5D4, D6W5D6, Q49AK9, Q53EU9, Q53S39, Q53S77, Q53TU1, Q86Y07, Q86Y08, Q86Y09, Q86Y10, Q86Y11, Q86Y12, Q8IXI5, Q99987

UniProtKB/TrEMBL

Q05CR6

Conserved Domains (2) summary

COG0515
Location:29 → 421

SPS1; Serine/threonine protein kinase [Signal transduction mechanisms]

cd14123
Location:16 → 314

STKc_VRK2; Catalytic domain of the Serine/Threonine protein kinase, Vaccinia Related Kinase 2
NM_001130481.2 → NP_001123953.1 serine/threonine-protein kinase VRK2 isoform 1

See identical proteins and their annotated locations for NP_001123953.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) differs in the 5' UTR compared to variant 1. Variants 1, 2, 3, and 8 encode the same isoform (1, also known as VRK2A).

Source sequence(s)

AK311205, AY228367, BC027854

Consensus CDS

CCDS1859.1

UniProtKB/Swiss-Prot

B4DKL0, D6W5D4, D6W5D6, Q49AK9, Q53EU9, Q53S39, Q53S77, Q53TU1, Q86Y07, Q86Y08, Q86Y09, Q86Y10, Q86Y11, Q86Y12, Q8IXI5, Q99987

UniProtKB/TrEMBL

Q05CR6

Conserved Domains (2) summary

COG0515
Location:29 → 421

SPS1; Serine/threonine protein kinase [Signal transduction mechanisms]

cd14123
Location:16 → 314

STKc_VRK2; Catalytic domain of the Serine/Threonine protein kinase, Vaccinia Related Kinase 2
NM_001130482.2 → NP_001123954.1 serine/threonine-protein kinase VRK2 isoform 2

See identical proteins and their annotated locations for NP_001123954.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at a downstream in-frame start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus than isoform 1.

Source sequence(s)

AK223540, AK311205, AY228369, DB227029

Consensus CDS

CCDS46292.1

UniProtKB/TrEMBL

Q05CR6

Related

ENSP00000398323.2, ENST00000440705.6

Conserved Domains (2) summary

COG0515
Location:6 → 398

SPS1; Serine/threonine protein kinase [Signal transduction mechanisms]

cl21453
Location:1 → 291

PKc_like; Protein Kinases, catalytic domain
NM_001130483.2 → NP_001123955.1 serine/threonine-protein kinase VRK2 isoform 3

See identical proteins and their annotated locations for NP_001123955.1

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR and contains an alternate exon in the 3' coding region, which results in a frameshift, compared to variant 1. The encoded isoform (3) has a shorter and distinct C-terminus, compared to isoform 1. Variants 5 and 9 encode the same isoform (3, also known as VRK2B).

Source sequence(s)

AK311205, AY228372, DB227029

Consensus CDS

CCDS46291.1

UniProtKB/TrEMBL

Q05CR6

Conserved Domains (1) summary

cl21453
Location:16 → 314

PKc_like; Protein Kinases, catalytic domain
NM_001288836.1 → NP_001275765.1 serine/threonine-protein kinase VRK2 isoform 4

See identical proteins and their annotated locations for NP_001275765.1

Status: REVIEWED

Description

Transcript Variant: This variant (6) uses an alternate splice site and contains an alternate exon in the 5' region, compared to variant 1. It initiates translation at a downstream in-frame start codon. The encoded isoform (4) has a shorter N-terminus than isoform 1. Variants 6 and 7 encode the same isoform (4).

Source sequence(s)

AK296611, AK311205, DB227029

Consensus CDS

CCDS46293.1

UniProtKB/Swiss-Prot

Q86Y07

Conserved Domains (2) summary

COG0515
Location:1 → 303

SPS1; Serine/threonine protein kinase [Signal transduction mechanisms]

cl21453
Location:1 → 196

PKc_like; Protein Kinases, catalytic domain
NM_001288837.2 → NP_001275766.1 serine/threonine-protein kinase VRK2 isoform 1

See identical proteins and their annotated locations for NP_001275766.1

Status: REVIEWED

Description

Transcript Variant: This variant (8) represents use of an alternate upstream promoter and differs in the 5' UTR, compared to variant 1. Variants 1, 2, 3, and 8 encode the same isoform (1, also known as VRK2A).

Source sequence(s)

AC068193, AK307113, AK311205, BC036434

Consensus CDS

CCDS1859.1

UniProtKB/Swiss-Prot

B4DKL0, D6W5D4, D6W5D6, Q49AK9, Q53EU9, Q53S39, Q53S77, Q53TU1, Q86Y07, Q86Y08, Q86Y09, Q86Y10, Q86Y11, Q86Y12, Q8IXI5, Q99987

UniProtKB/TrEMBL

Q05CR6

Related

ENSP00000408002.2, ENST00000435505.6

Conserved Domains (2) summary

COG0515
Location:29 → 421

SPS1; Serine/threonine protein kinase [Signal transduction mechanisms]

cd14123
Location:16 → 314

STKc_VRK2; Catalytic domain of the Serine/Threonine protein kinase, Vaccinia Related Kinase 2
NM_001288838.2 → NP_001275767.1 serine/threonine-protein kinase VRK2 isoform 3

See identical proteins and their annotated locations for NP_001275767.1

Status: REVIEWED

Description

Transcript Variant: This variant (9) represents use of an alternate upstream promoter, differs in the 5' UTR, and contains an alternate exon in the 3' coding region, which results in a frameshift, compared to variant 1. The encoded isoform (3) has a shorter and distinct C-terminus, compared to isoform 1. Variants 5 and 9 encode the same isoform (3, also known as VRK2B).

Source sequence(s)

AC068193, AK292727, AK311205, AY228372, BC036434

Consensus CDS

CCDS46291.1

UniProtKB/TrEMBL

Q05CR6

Related

ENSP00000402375.2, ENST00000417641.6

Conserved Domains (1) summary

cl21453
Location:16 → 314

PKc_like; Protein Kinases, catalytic domain
NM_001288839.2 → NP_001275768.1 serine/threonine-protein kinase VRK2 isoform 4

See identical proteins and their annotated locations for NP_001275768.1

Status: REVIEWED

Description

Transcript Variant: This variant (7) lacks an exon in the 5' region, compared to variant 1, and initiates translation at a downstream in-frame start codon. The encoded isoform (4) has a shorter N-terminus than isoform 1. Variants 6 and 7 encode the same isoform (4).

Source sequence(s)

AC007250, AC073215, AY228371

Consensus CDS

CCDS46293.1

UniProtKB/Swiss-Prot

Q86Y07

Related

ENSP00000404156.3, ENST00000412104.6

Conserved Domains (2) summary

COG0515
Location:1 → 303

SPS1; Serine/threonine protein kinase [Signal transduction mechanisms]

cl21453
Location:1 → 196

PKc_like; Protein Kinases, catalytic domain
NM_006296.7 → NP_006287.2 serine/threonine-protein kinase VRK2 isoform 1

See identical proteins and their annotated locations for NP_006287.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1). Variants 1, 2, 3, and 8 encode the same isoform (1, also known as VRK2A).

Source sequence(s)

AK223540, BC027854

Consensus CDS

CCDS1859.1

UniProtKB/Swiss-Prot

B4DKL0, D6W5D4, D6W5D6, Q49AK9, Q53EU9, Q53S39, Q53S77, Q53TU1, Q86Y07, Q86Y08, Q86Y09, Q86Y10, Q86Y11, Q86Y12, Q8IXI5, Q99987

UniProtKB/TrEMBL

Q05CR6

Related

ENSP00000342381.4, ENST00000340157.9

Conserved Domains (2) summary

COG0515
Location:29 → 421

SPS1; Serine/threonine protein kinase [Signal transduction mechanisms]

cd14123
Location:16 → 314

STKc_VRK2; Catalytic domain of the Serine/Threonine protein kinase, Vaccinia Related Kinase 2

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p14 Primary Assembly

Range

57907592..58159920

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005264540.5 → XP_005264597.1 serine/threonine-protein kinase VRK2 isoform X1

See identical proteins and their annotated locations for XP_005264597.1

UniProtKB/Swiss-Prot

B4DKL0, D6W5D4, D6W5D6, Q49AK9, Q53EU9, Q53S39, Q53S77, Q53TU1, Q86Y07, Q86Y08, Q86Y09, Q86Y10, Q86Y11, Q86Y12, Q8IXI5, Q99987

UniProtKB/TrEMBL

Q05CR6

Conserved Domains (2) summary

COG0515
Location:29 → 421

SPS1; Serine/threonine protein kinase [Signal transduction mechanisms]

cd14123
Location:16 → 314

STKc_VRK2; Catalytic domain of the Serine/Threonine protein kinase, Vaccinia Related Kinase 2
XM_006712091.5 → XP_006712154.1 serine/threonine-protein kinase VRK2 isoform X3

See identical proteins and their annotated locations for XP_006712154.1

UniProtKB/TrEMBL

Q05CR6

Conserved Domains (1) summary

cl21453
Location:16 → 314

PKc_like; Protein Kinases, catalytic domain
XM_006712090.5 → XP_006712153.1 serine/threonine-protein kinase VRK2 isoform X2

See identical proteins and their annotated locations for XP_006712153.1

UniProtKB/TrEMBL

Q05CR6

Related

ENSP00000497378.1, ENST00000648897.1

Conserved Domains (1) summary

cl21453
Location:16 → 314

PKc_like; Protein Kinases, catalytic domain
XM_011533092.4 → XP_011531394.1 serine/threonine-protein kinase VRK2 isoform X1

See identical proteins and their annotated locations for XP_011531394.1

UniProtKB/Swiss-Prot

B4DKL0, D6W5D4, D6W5D6, Q49AK9, Q53EU9, Q53S39, Q53S77, Q53TU1, Q86Y07, Q86Y08, Q86Y09, Q86Y10, Q86Y11, Q86Y12, Q8IXI5, Q99987

UniProtKB/TrEMBL

Q05CR6

Conserved Domains (2) summary

COG0515
Location:29 → 421

SPS1; Serine/threonine protein kinase [Signal transduction mechanisms]

cd14123
Location:16 → 314

STKc_VRK2; Catalytic domain of the Serine/Threonine protein kinase, Vaccinia Related Kinase 2
XM_047445748.1 → XP_047301704.1 serine/threonine-protein kinase VRK2 isoform X4
XM_047445747.1 → XP_047301703.1 serine/threonine-protein kinase VRK2 isoform X4
XM_047445745.1 → XP_047301701.1 serine/threonine-protein kinase VRK2 isoform X4

Alternate T2T-CHM13v2.0

Genomic

NC_060926.1 Alternate T2T-CHM13v2.0

Range

57912292..58164754

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054343751.1 → XP_054199726.1 serine/threonine-protein kinase VRK2 isoform X1
XM_054343754.1 → XP_054199729.1 serine/threonine-protein kinase VRK2 isoform X3

UniProtKB/TrEMBL

A8K9L2
XM_054343753.1 → XP_054199728.1 serine/threonine-protein kinase VRK2 isoform X2
XM_054343752.1 → XP_054199727.1 serine/threonine-protein kinase VRK2 isoform X1
XM_054343757.1 → XP_054199732.1 serine/threonine-protein kinase VRK2 isoform X4
XM_054343756.1 → XP_054199731.1 serine/threonine-protein kinase VRK2 isoform X4
XM_054343755.1 → XP_054199730.1 serine/threonine-protein kinase VRK2 isoform X4