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

    Gene ID: 51231, updated on 4-Jan-2025

    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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    See VRK3 in Genome Data Viewer
    Location:
    19q13.33
    Exon count:
    18
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 19 NC_000019.10 (49976468..50025372, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 19 NC_060943.1 (52976576..53025796, complement)
    RS_2024_09 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 (gene/pseudogene) 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: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 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. 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
    3. 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
    4. 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
    5. 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

    See all (50) 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)

    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 DNA damage response IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in negative regulation of ERK1 and ERK2 cascade IEA
    Inferred from Electronic Annotation
    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
    Names
    inactive serine/threonine-protein kinase VRK3
    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

      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

      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

      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_2024_08

    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  serine/threonine-protein kinase VRK3 isoform X3

      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  serine/threonine-protein kinase VRK3 isoform X1

      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  serine/threonine-protein kinase VRK3 isoform X1

      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  serine/threonine-protein kinase VRK3 isoform X3

      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  serine/threonine-protein kinase VRK3 isoform X4

      UniProtKB/TrEMBL
      M0R073

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

      UniProtKB/TrEMBL
      M0QYA8

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

      UniProtKB/TrEMBL
      M0R073

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

      UniProtKB/TrEMBL
      M0QYA8

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

      UniProtKB/TrEMBL
      B4E0U5
      Related
      ENSP00000469802.1, ENST00000596121.5

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

      UniProtKB/TrEMBL
      B4E0U5

    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  serine/threonine-protein kinase VRK3 isoform X3

      UniProtKB/TrEMBL
      M0R073

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

      UniProtKB/Swiss-Prot
      A6NEG5, A8KA53, Q502Y2, Q8IV63, Q9P2V8
      UniProtKB/TrEMBL
      M0QYA8

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

      UniProtKB/Swiss-Prot
      A6NEG5, A8KA53, Q502Y2, Q8IV63, Q9P2V8
      UniProtKB/TrEMBL
      M0QYA8

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

      UniProtKB/TrEMBL
      M0R073

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

      UniProtKB/TrEMBL
      M0R073

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

      UniProtKB/TrEMBL
      M0QYA8

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

      UniProtKB/TrEMBL
      M0R073

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

      UniProtKB/TrEMBL
      M0QYA8

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

      UniProtKB/TrEMBL
      B4E0U5

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

      UniProtKB/TrEMBL
      B4E0U5

    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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