Human Gene VRK2 (uc002rzo.2)
  Description: Homo sapiens vaccinia related kinase 2 (VRK2), transcript variant 3, mRNA.
RefSeq Summary (NM_001130482): 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].
Transcript (Including UTRs)
   Position: hg19 chr2:58,134,786-58,387,055 Size: 252,270 Total Exon Count: 16 Strand: +
Coding Region
   Position: hg19 chr2:58,275,967-58,386,828 Size: 110,862 Coding Exon Count: 12 

Page IndexSequence and LinksUniProtKB CommentsPrimersGenetic AssociationsMalaCards
CTDGene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein Structure
Other SpeciesGO AnnotationsmRNA DescriptionsPathwaysOther NamesModel Information
Methods
Data last updated at UCSC: 2013-06-14

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr2:58,134,786-58,387,055)mRNA (may differ from genome)Protein (508 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
AlphaFoldBioGPSEnsemblEntrez GeneExonPrimerGeneCards
H-INVHGNCLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: VRK2_HUMAN
DESCRIPTION: RecName: Full=Serine/threonine-protein kinase VRK2; EC=2.7.11.1; AltName: Full=Vaccinia-related kinase 2;
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.
FUNCTION: 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.
CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.
ENZYME REGULATION: RAN inhibits its autophosphorylation and its ability to phosphorylate histone H3.
SUBUNIT: Isoform 1 interacts with MAP3K7, MAP2K7, MAP2K1 and KSR1. Isoform 1 and isoform 2 interact with RAN and MAPK8IP1. Isoform 1 interacts with Epstein-Barr virus BHRF1; this interaction is involved in protecting cells from apoptosis.
INTERACTION: P03182:BHRF1 (xeno); NbExp=7; IntAct=EBI-1207615, EBI-1207659; Q8IVT5:KSR1; NbExp=4; IntAct=EBI-1207615, EBI-486984; Q61097:Ksr1 (xeno); NbExp=8; IntAct=EBI-1207633, EBI-1536336; Q02750:MAP2K1; NbExp=2; IntAct=EBI-1207615, EBI-492564; Q62073:Map3k7 (xeno); NbExp=3; IntAct=EBI-1207633, EBI-1775345; Q9WVI9-2:Mapk8ip1 (xeno); NbExp=2; IntAct=EBI-1207636, EBI-288464; P62826:RAN; NbExp=2; IntAct=EBI-1207633, EBI-286642; Q8CF89:Tab1 (xeno); NbExp=2; IntAct=EBI-1207633, EBI-1778503;
SUBCELLULAR LOCATION: Isoform 1: Cytoplasm. Endoplasmic reticulum membrane; Single-pass type IV membrane protein (Potential). Mitochondrion membrane; Single-pass type IV membrane protein (Potential).
SUBCELLULAR LOCATION: Isoform 2: Cytoplasm. Nucleus.
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.
PTM: Isoform 1 and isoform 2 are autophosphorylated.
SIMILARITY: Belongs to the protein kinase superfamily. CK1 Ser/Thr protein kinase family. VRK subfamily.
SIMILARITY: Contains 1 protein kinase domain.
SEQUENCE CAUTION: Sequence=CAD54446.2; Type=Miscellaneous discrepancy; Note=Aberrant splicing;

-  Primer design for this transcript
 

Primer3Plus can design qPCR Primers that straddle exon-exon-junctions, which amplify only cDNA, not genomic DNA.
Click here to load the transcript sequence and exon structure into Primer3Plus

Exonprimer can design one pair of Sanger sequencing primers around every exon, located in non-genic sequence.
Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): VRK2
CDC HuGE Published Literature: VRK2
Positive Disease Associations: Bipolar Disorder , Insulin , Respiration Disorders , schizophrenia
Related Studies:
  1. Bipolar Disorder
    , , . [PubMed 0]
  2. Bipolar Disorder
    , , . [PubMed 0]
  3. Insulin
    , , . [PubMed 0]
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: VRK2
Diseases sorted by gene-association score: vaccinia (47), schizophrenia (2), chromosome 2p16.1-p15 deletion syndrome (2)

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 14.44 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 139.42 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
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-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -201.65745-0.271 Picture PostScript Text
3' UTR -42.10227-0.185 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR011009 - Kinase-like_dom
IPR000719 - Prot_kinase_cat_dom
IPR008271 - Ser/Thr_kinase_AS

Pfam Domains:
PF00069 - Protein kinase domain
PF07714 - Protein tyrosine kinase

SCOP Domains:
56112 - Protein kinase-like (PK-like)

Protein Data Bank (PDB) 3-D Structure
MuPIT help
2V62 - X-ray MuPIT


ModBase Predicted Comparative 3D Structure on Q86Y07
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The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologNo orthologNo orthologNo orthologNo orthologNo ortholog
Gene Details     
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-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0000166 nucleotide binding
GO:0004672 protein kinase activity
GO:0004674 protein serine/threonine kinase activity
GO:0005515 protein binding
GO:0005524 ATP binding
GO:0016301 kinase activity
GO:0016740 transferase activity
GO:0019901 protein kinase binding
GO:0019904 protein domain specific binding

Biological Process:
GO:0006468 protein phosphorylation
GO:0008360 regulation of cell shape
GO:0016032 viral process
GO:0016310 phosphorylation
GO:0018105 peptidyl-serine phosphorylation
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:0005739 mitochondrion
GO:0005783 endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane
GO:0016020 membrane
GO:0016021 integral component of membrane
GO:0031966 mitochondrial membrane
GO:0032991 macromolecular complex


-  Descriptions from all associated GenBank mRNAs
  BC036434 - Homo sapiens vaccinia related kinase 2, mRNA (cDNA clone IMAGE:4815217), with apparent retained intron.
AK307113 - Homo sapiens cDNA, FLJ97061.
AK292727 - Homo sapiens cDNA FLJ76729 complete cds, highly similar to Homo sapiens vaccinia related kinase 2 isoform 6 (VRK2) mRNA.
AK295193 - Homo sapiens cDNA FLJ53040 complete cds, highly similar to Serine/threonine-protein kinase VRK2 (EC 2.7.11.1).
AK296611 - Homo sapiens cDNA FLJ57314 complete cds, highly similar to Serine/threonine-protein kinase VRK2 (EC 2.7.11.1).
BC027854 - Homo sapiens vaccinia related kinase 2, mRNA (cDNA clone MGC:34431 IMAGE:5221315), complete cds.
AB000450 - Homo sapiens mRNA for VRK2, complete cds.
AJ512204 - Homo sapiens mRNA for vaccinia-related kinase 2 (VRK2 gene), splice variant B.
AY228367 - Homo sapiens vaccinia related kinase 2 isoform 1 (VRK2) mRNA, complete cds; alternatively spliced.
AY228368 - Homo sapiens vaccinia related kinase 2 isoform 2 (VRK2) mRNA, complete cds; alternatively spliced.
AY228370 - Homo sapiens vaccinia related kinase 2 isoform 4 (VRK2) mRNA, complete cds; alternatively spliced.
AY228371 - Homo sapiens vaccinia related kinase 2 isoform 5 (VRK2) mRNA, complete cds; alternatively spliced.
AY228372 - Homo sapiens vaccinia related kinase 2 isoform 6 (VRK2) mRNA, complete cds; alternatively spliced.
AY228369 - Homo sapiens vaccinia related kinase 2 isoform 3 (VRK2) mRNA, complete cds; alternatively spliced.
AK223540 - Homo sapiens mRNA for vaccinia related kinase 2 variant, clone: FCC125C11.
AK058199 - Homo sapiens cDNA FLJ25470 fis, clone TST09537, highly similar to Homo sapiens mRNA for VRK2.
BC021663 - Homo sapiens vaccinia related kinase 2, mRNA (cDNA clone IMAGE:3683008), partial cds.
AB529186 - Synthetic construct DNA, clone: pF1KE0964, Homo sapiens VRK2 gene for vaccinia related kinase 2, without stop codon, in Flexi system.
DQ890932 - Synthetic construct clone IMAGE:100003562; FLH167636.01X; RZPDo839D0590D vaccinia related kinase 2 (VRK2) gene, encodes complete protein.
DQ894094 - Synthetic construct Homo sapiens clone IMAGE:100008554; FLH167632.01L; RZPDo839D0589D vaccinia related kinase 2 (VRK2) gene, encodes complete protein.
AK311205 - Homo sapiens cDNA, FLJ18247.
JD300296 - Sequence 281320 from Patent EP1572962.
CU691101 - Synthetic construct Homo sapiens gateway clone IMAGE:100021418 3' read FANCL mRNA.

-  Biochemical and Signaling Pathways
  Reactome (by CSHL, EBI, and GO)

Protein Q86Y07 (Reactome details) participates in the following event(s):

R-HSA-2995389 ANKLE2 binds VRK1 or VRK2
R-HSA-2993898 VRK1/VRK2 phosphorylate BANF1
R-HSA-2995383 Initiation of Nuclear Envelope Reformation
R-HSA-2993913 Clearance of Nuclear Envelope Membranes from Chromatin
R-HSA-2995410 Nuclear Envelope Reassembly
R-HSA-2980766 Nuclear Envelope Breakdown
R-HSA-68882 Mitotic Anaphase
R-HSA-68875 Mitotic Prophase
R-HSA-2555396 Mitotic Metaphase and Anaphase
R-HSA-68886 M Phase
R-HSA-69278 Cell Cycle (Mitotic)
R-HSA-1640170 Cell Cycle

-  Other Names for This Gene
  Alternate Gene Symbols: B4DKL0, BC036434, D6W5D4, D6W5D6, NM_001130482, NP_001123954, Q49AK9, Q53EU9, Q53S39, Q53S77, Q53TU1, Q86Y07, Q86Y08, Q86Y09, Q86Y10, Q86Y11, Q86Y12, Q8IXI5, Q99987, VRK2_HUMAN
UCSC ID: uc002rzo.2
RefSeq Accession: NM_001130482
Protein: Q86Y07 (aka VRK2_HUMAN)
CCDS: CCDS46292.1, CCDS1859.1

-  Gene Model Information
 
category: coding nonsense-mediated-decay: no RNA accession: BC036434.1
exon count: 16CDS single in 3' UTR: no RNA size: 2487
ORF size: 1527CDS single in intron: no Alignment % ID: 99.92
txCdsPredict score: 2639.00frame shift in genome: no % Coverage: 98.35
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
Click here for a detailed description of the fields of the table above.

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.