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VRK3 VRK serine/threonine kinase 3 [ Homo sapiens (human) ]

Gene ID: 51231, updated on 12-May-2024

Summary

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Official Symbol
VRK3provided by HGNC
Official Full Name
VRK serine/threonine kinase 3provided by HGNC
Primary source
HGNC:HGNC:18996
See related
Ensembl:ENSG00000105053 MIM:619771; AllianceGenome:HGNC:18996
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. In both human and mouse, this gene has substitutions at several residues within the ATP binding motifs that in other kinases have been shown to be required for catalysis. In vitro assays indicate the protein lacks phosphorylation activity. The protein, however, likely retains its substrate binding capability. This gene is widely expressed in human tissues and its protein localizes to the nucleus. Alternative splicing results in multiple transcripts encoding different isoforms. [provided by RefSeq, Jul 2008]
Expression
Broad expression in testis (RPKM 36.5), small intestine (RPKM 9.1) and 24 other tissues See more
Orthologs
mouse all
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Genomic context

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Location:
19q13.33
Exon count:
18
Annotation release Status Assembly Chr Location
RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (49976468..50025372, complement)
RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (52976576..53025796, complement)
105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 19 NC_000019.9 (50479725..50528629, complement)

Chromosome 19 - NC_000019.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124904745 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:50474918-50475418 Neighboring gene sialic acid binding Ig like lectin 16 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14970 Neighboring gene ReSE screen-validated silencer GRCh37_chr19:50490479-50490646 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:50497521-50498022 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr19:50498023-50498522 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 10949 Neighboring gene H3K27ac hESC enhancer GRCh37_chr19:50527935-50528436 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14971 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14972 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14973 Neighboring gene zinc finger protein 473 Neighboring gene uncharacterized LOC124904744 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 14974 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr19:50554133-50554813 Neighboring gene ZNF473 cis regulating lncRNA Neighboring gene zinc finger protein 420-like

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • Project title: 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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Related articles in PubMed

  1. A kinome-wide shRNA screen uncovers vaccinia-related kinase 3 (VRK3) as an essential gene for diffuse intrinsic pontine glioma survival. Silva-Evangelista C, et al. Oncogene, 2019 Sep. PMID 31324890
  2. RNF144a induces ERK-dependent cell death under oxidative stress via downregulation of vaccinia-related kinase 3. Han SH, et al. J Cell Sci, 2020 Nov 9. PMID 33067254
  3. Autism-like behavior caused by deletion of vaccinia-related kinase 3 is improved by TrkB stimulation. Kang MS, et al. J Exp Med, 2017 Oct 2. PMID 28899869, Free PMC Article
  4. Vaccinia-related kinase 3 (VRK3) sets the circadian period and amplitude by affecting the subcellular localization of clock proteins in mammalian cells. Park N, et al. Biochem Biophys Res Commun, 2017 May 27. PMID 28412365
  5. Structure of the pseudokinase VRK3 reveals a degraded catalytic site, a highly conserved kinase fold, and a putative regulatory binding site. Scheeff ED, et al. Structure, 2009 Jan 14. PMID 19141289, Free PMC Article

See all (47) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. RNF144a induces ERK-dependent cell death under oxidative stress via downregulation of vaccinia-related kinase 3.
    Title: RNF144a induces ERK-dependent cell death under oxidative stress via downregulation of vaccinia-related kinase 3.
  2. VRK3 is an interesting and promising target in Diffuse intrinsic pontine glioma.
    Title: A kinome-wide shRNA screen uncovers vaccinia-related kinase 3 (VRK3) as an essential gene for diffuse intrinsic pontine glioma survival.
  3. Nuclear HSP70 leads to enhancement of vaccinia H1-related phosphatase (VHR) activity via protein-protein interaction rather than its molecular chaperone activity, thereby suppressing excessive ERK activation. Downregulation of either VRK3 or HSP70 rendered cells vulnerable to glutamate-induced apoptosis.
    Title: VRK3-mediated nuclear localization of HSP70 prevents glutamate excitotoxicity-induced apoptosis and Aβ accumulation via enhancement of ERK phosphatase VHR activity.
  4. this study not only provides a resource for investigating the unidentified functions of VRK1/VRK3, but also an insight into the regulatory roles of VRK1/VRK3 in biological processes.
    Title: Comparative Interactomes of VRK1 and VRK3 with Their Distinct Roles in the Cell Cycle of Liver Cancer.
  5. Stress-induced nuclear translocation of CDK5 suppresses neuronal death by downregulating ERK activation via VRK3 phosphorylation
    Title: Stress-induced nuclear translocation of CDK5 suppresses neuronal death by downregulating ERK activation via VRK3 phosphorylation.
  6. Finally, downregulation of hvrk3 using siRNA reduced the amplitude and lengthened the period of the cellular bioluminescence rhythm. Taken together, these data suggest that VRK3 plays a role in setting the amplitude and period length of circadian rhythms in mammalian cells.
    Title: Vaccinia-related kinase 3 (VRK3) sets the circadian period and amplitude by affecting the subcellular localization of clock proteins in mammalian cells.
  7. These data suggest that VRK3-mediated phosphorylation of BAF may facilitate DNA replication or gene expression by facilitating the dissociation of nuclear envelope proteins and chromatin during interphase.
    Title: Presumed pseudokinase VRK3 functions as a BAF kinase.
  8. Data from molecular dynamic simulations suggest that bivalent cations play key structural roles in stabilization of VRK1/VRK2; bivalent cations have no obvious effects on VRK3. These kinases are targets in search for antineoplastic agents. [REVIEW]
    Title: Role of bivalent cations in structural stabilities of new drug targets--vaccinia-related kinases (VRK) from molecular dynamics simulations.
Submit: New GeneRIF Correction

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Genotypes

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables ATP binding IEA
Inferred from Electronic Annotation
more info
  
enables protein binding IPI
Inferred from Physical Interaction
more info
 PubMed 
enables protein phosphatase binding IDA
Inferred from Direct Assay
more info
 PubMed 
enables protein serine/threonine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in negative regulation of ERK1 and ERK2 cascade IEA
Inferred from Electronic Annotation
more info
  
involved_in peptidyl-serine phosphorylation IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in signal transduction IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in skeletal muscle tissue development IGI
Inferred from Genetic Interaction
more info
 PubMed 
Component Evidence Code Pubs
is_active_in cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in cytoplasm IEA
Inferred from Electronic Annotation
more info
  
located_in intracellular membrane-bounded organelle IDA
Inferred from Direct Assay
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
located_in nucleus HDA PubMed 
is_active_in nucleus IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
serine/threonine-protein kinase VRK3; inactive serine/threonine-protein kinase VRK3
Names
serine/threonine-protein pseudokinase VRK3
vaccinia related kinase 3
NP_001020949.1
NP_001295349.1
NP_057524.3
XP_005259028.1
XP_005259029.1
XP_006723300.1
XP_006723301.1
XP_047294854.1
XP_047294855.1
XP_047294856.1
XP_047294857.1
XP_047294858.1
XP_047294859.1
XP_054177127.1
XP_054177128.1
XP_054177129.1
XP_054177130.1
XP_054177131.1
XP_054177132.1
XP_054177133.1
XP_054177134.1
XP_054177135.1
XP_054177136.1

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.

mRNA and Protein(s)

  1. NM_001025778.2 → NP_001020949.1  serine/threonine-protein kinase VRK3 isoform 2

    See identical proteins and their annotated locations for NP_001020949.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon in the 5' coding region, compared to variant 1, resulting in a protein (isoform 2) that is shorter than isoform 1.
    Source sequence(s)
    AC011452, AV706241
    Consensus CDS
    CCDS33076.1
    UniProtKB/TrEMBL
    M0R073
    Related
    ENSP00000366210.1, ENST00000377011.6
    Conserved Domains (4) summary
    COG0515
    Location:161 → 417
    SPS1; Serine/threonine protein kinase [Signal transduction mechanisms]
    pfam12773
    Location:5 → 31
    DZR; Double zinc ribbon
    pfam13240
    Location:4 → 26
    zinc_ribbon_2; zinc-ribbon domain
    cl21453
    Location:105 → 407
    PKc_like; Protein Kinases, catalytic domain

  2. NM_001308420.3 → NP_001295349.1  serine/threonine-protein kinase VRK3 isoform 3

    See identical proteins and their annotated locations for NP_001295349.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3) lacks several exons and uses an alternate 3' terminal exon that results in a different 3' UTR and novel 3' coding region compared to variant 1. It encodes isoform 3, which is shorter than and has a distinct C-terminus compared to isoform 1.
    Source sequence(s)
    BC023556, BP335032
    Consensus CDS
    CCDS77334.1
    UniProtKB/TrEMBL
    M0QYA8
    Related
    ENSP00000472541.1, ENST00000594092.5
    Conserved Domains (5) summary
    COG0515
    Location:211 → 412
    SPS1; Serine/threonine protein kinase [Signal transduction mechanisms]
    pfam12773
    Location:5 → 31
    DZR; Double zinc ribbon
    pfam13240
    Location:4 → 26
    zinc_ribbon_2; zinc-ribbon domain
    pfam15087
    Location:82 → 150
    DUF4551; Protein of unknown function (DUF4551)
    cl21453
    Location:155 → 406
    PKc_like; Protein Kinases, catalytic domain

  3. NM_016440.4 → NP_057524.3  serine/threonine-protein kinase VRK3 isoform 1

    See identical proteins and their annotated locations for NP_057524.3

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AC011452, AF514788, AV706241
    Consensus CDS
    CCDS12791.1
    UniProtKB/Swiss-Prot
    A6NEG5, A8KA53, Q502Y2, Q8IV63, Q9P2V8
    UniProtKB/TrEMBL
    M0QYA8
    Related
    ENSP00000324636.2, ENST00000316763.8
    Conserved Domains (5) summary
    COG0515
    Location:211 → 467
    SPS1; Serine/threonine protein kinase [Signal transduction mechanisms]
    pfam12773
    Location:5 → 31
    DZR; Double zinc ribbon
    pfam13240
    Location:4 → 26
    zinc_ribbon_2; zinc-ribbon domain
    pfam15087
    Location:82 → 150
    DUF4551; Protein of unknown function (DUF4551)
    cl21453
    Location:155 → 457
    PKc_like; Protein Kinases, catalytic domain

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000019.10 Reference GRCh38.p14 Primary Assembly

    Range
    49976468..50025372 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_005258972.5 → XP_005259029.1  inactive serine/threonine-protein kinase VRK3 isoform X3

    See identical proteins and their annotated locations for XP_005259029.1

    UniProtKB/TrEMBL
    M0R073
    Related
    ENSP00000470156.1, ENST00000601341.5
    Conserved Domains (4) summary
    COG0515
    Location:161 → 417
    SPS1; Serine/threonine protein kinase [Signal transduction mechanisms]
    pfam12773
    Location:5 → 31
    DZR; Double zinc ribbon
    pfam13240
    Location:4 → 26
    zinc_ribbon_2; zinc-ribbon domain
    cl21453
    Location:105 → 407
    PKc_like; Protein Kinases, catalytic domain

  2. XM_005258971.4 → XP_005259028.1  inactive serine/threonine-protein kinase VRK3 isoform X1

    See identical proteins and their annotated locations for XP_005259028.1

    UniProtKB/Swiss-Prot
    A6NEG5, A8KA53, Q502Y2, Q8IV63, Q9P2V8
    UniProtKB/TrEMBL
    M0QYA8
    Related
    ENSP00000469880.1, ENST00000599538.5
    Conserved Domains (5) summary
    COG0515
    Location:211 → 467
    SPS1; Serine/threonine protein kinase [Signal transduction mechanisms]
    pfam12773
    Location:5 → 31
    DZR; Double zinc ribbon
    pfam13240
    Location:4 → 26
    zinc_ribbon_2; zinc-ribbon domain
    pfam15087
    Location:82 → 150
    DUF4551; Protein of unknown function (DUF4551)
    cl21453
    Location:155 → 457
    PKc_like; Protein Kinases, catalytic domain

  3. XM_006723237.4 → XP_006723300.1  inactive serine/threonine-protein kinase VRK3 isoform X1

    See identical proteins and their annotated locations for XP_006723300.1

    UniProtKB/Swiss-Prot
    A6NEG5, A8KA53, Q502Y2, Q8IV63, Q9P2V8
    UniProtKB/TrEMBL
    M0QYA8
    Conserved Domains (5) summary
    COG0515
    Location:211 → 467
    SPS1; Serine/threonine protein kinase [Signal transduction mechanisms]
    pfam12773
    Location:5 → 31
    DZR; Double zinc ribbon
    pfam13240
    Location:4 → 26
    zinc_ribbon_2; zinc-ribbon domain
    pfam15087
    Location:82 → 150
    DUF4551; Protein of unknown function (DUF4551)
    cl21453
    Location:155 → 457
    PKc_like; Protein Kinases, catalytic domain

  4. XM_006723238.5 → XP_006723301.1  inactive serine/threonine-protein kinase VRK3 isoform X3

    See identical proteins and their annotated locations for XP_006723301.1

    UniProtKB/TrEMBL
    M0R073
    Conserved Domains (4) summary
    COG0515
    Location:161 → 417
    SPS1; Serine/threonine protein kinase [Signal transduction mechanisms]
    pfam12773
    Location:5 → 31
    DZR; Double zinc ribbon
    pfam13240
    Location:4 → 26
    zinc_ribbon_2; zinc-ribbon domain
    cl21453
    Location:105 → 407
    PKc_like; Protein Kinases, catalytic domain

  5. XM_047438900.1 → XP_047294856.1  inactive serine/threonine-protein kinase VRK3 isoform X4

  6. XM_047438898.1 → XP_047294854.1  inactive serine/threonine-protein kinase VRK3 isoform X2

  7. XM_047438901.1 → XP_047294857.1  inactive serine/threonine-protein kinase VRK3 isoform X4

  8. XM_047438899.1 → XP_047294855.1  inactive serine/threonine-protein kinase VRK3 isoform X2

  9. XM_047438902.1 → XP_047294858.1  inactive serine/threonine-protein kinase VRK3 isoform X5

    Related
    ENSP00000469802.1, ENST00000596121.5

  10. XM_047438903.1 → XP_047294859.1  inactive serine/threonine-protein kinase VRK3 isoform X5

RNA

  1. XR_007066860.1 RNA Sequence

  2. XR_007066859.1 RNA Sequence

  3. XR_007066855.1 RNA Sequence

  4. XR_007066857.1 RNA Sequence

  5. XR_007066858.1 RNA Sequence

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060943.1 Alternate T2T-CHM13v2.0

    Range
    52976576..53025796 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054321156.1 → XP_054177131.1  inactive serine/threonine-protein kinase VRK3 isoform X3

  2. XM_054321152.1 → XP_054177127.1  inactive serine/threonine-protein kinase VRK3 isoform X1

    UniProtKB/Swiss-Prot
    A6NEG5, A8KA53, Q502Y2, Q8IV63, Q9P2V8

  3. XM_054321153.1 → XP_054177128.1  inactive serine/threonine-protein kinase VRK3 isoform X1

    UniProtKB/Swiss-Prot
    A6NEG5, A8KA53, Q502Y2, Q8IV63, Q9P2V8

  4. XM_054321157.1 → XP_054177132.1  inactive serine/threonine-protein kinase VRK3 isoform X3

  5. XM_054321158.1 → XP_054177133.1  inactive serine/threonine-protein kinase VRK3 isoform X4

  6. XM_054321154.1 → XP_054177129.1  inactive serine/threonine-protein kinase VRK3 isoform X2

  7. XM_054321159.1 → XP_054177134.1  inactive serine/threonine-protein kinase VRK3 isoform X4

  8. XM_054321155.1 → XP_054177130.1  inactive serine/threonine-protein kinase VRK3 isoform X2

  9. XM_054321160.1 → XP_054177135.1  inactive serine/threonine-protein kinase VRK3 isoform X5

  10. XM_054321161.1 → XP_054177136.1  inactive serine/threonine-protein kinase VRK3 isoform X5

RNA

  1. XR_008485164.1 RNA Sequence

  2. XR_008485163.1 RNA Sequence

  3. XR_008485160.1 RNA Sequence

  4. XR_008485161.1 RNA Sequence

  5. XR_008485162.1 RNA Sequence

Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q8IV63.2 GenPept UniProtKB/Swiss-Prot:Q8IV63

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