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FLASH GENE
Symbol VRK1 contributors: mct/npt/pgu - updated : 09-10-2013
HGNC name vaccinia related kinase 1
HGNC id 12718
Corresponding disease
PCH1 pontocerebellar hypoplasia 1
Location 14q32.2      Physical location : 97.263.683 - 97.347.950
Synonym name
  • vaccinia virus B1R-related kinase 1
  • serine/threonine-protein kinase VRK1
    • Synonym symbol(s) MGC117401, MGC138280, MGC142070, PCH1, PCH1A
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 84.27 kb     13 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned   linked   status provisional
    Map cen - D14S65 - D14S1019 - VRK1 - BDKRB2 - BDKRB1 - D14S267 - YY1 - D14S78 - D14S272 - CKB - AKT1 - qter
    Authors Gene Map
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    13 - 1720 - 396 - 2008 18713830
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestivesalivary gland   highly
    Nervousbrainhindbraincerebellum highly
    Urinarybladder   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / hematopoieticbone marrow  highly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    Text highly expressed in fetal liver, testis and thymus
  • in fetal brain and cerebellum
    • PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • a protein kinase domain
  • a dominant epitope located in C-terminal region, between AAs 333 and 396, which is detected by different antibodies
    • HOMOLOGY
    Homologene
    FAMILY
  • protein kinase superfamily
  • Ser/Thr protein kinase family
  • VRK subfamily
    • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule
    intracellular,nucleus,nucleoplasm
    intracellular,nucleus,nucleolus
    text
  • dispersed throughout the cell but not located on mitotic spindle or
    • chromatids during mitosis
  • mainly a nuclear protein, with a small fraction found in the cytoplasm and membrane compartments
  • most of the intracellular VRK1 protein is nuclear, but in some cells it is also detected in the cytosol, depending on the type of tissue (has a subcellular localization that can be regulated, thus adding an additional level of regulatory complexity to the VRK1 protein)
    • basic FUNCTION
  • serine/threonine kinase phosphorylating thr-18 of TP 53 and may thereby prevent the interaction between TP53 and MDM2
  • might play a role in cell cycle regulation and is likely to represent the beginning of a new control mechanism of cell cycle, particularly late in the G1-S phase
  • regulator of TP53 and other transcription factors related with cellular responses to stress
  • phosphorylates several transcription factors and is associated with proliferation phenotypes
  • immediate early response gene required for entry in G1, and due to its implication in normal cell proliferation and division
  • plays a key role in viral DNA replication
  • regulates cell cycle progression in the DNA replication period by inducing cyclin D1 (CCND1) expression
  • playing roles in neuronal development and maintenance
  • novel Ser/Thr kinase that is expressed constantly during interphase, and appears to play an important role during this period in the cell cycle
  • important role for VRK1 in cell proliferation and confirm that the need for VRK1 during gametogenesis is evolutionarily conserved
  • can increase cyclin D1 expression via the phosphorylation of the cAMP-response element-binding protein and has a major role in the G1/S transition
  • conserved role for VRK1 in coordinating proper chromosomal configuration in female meiosis
  • controls chromatin condensation by histone phosphorylation, nuclear envelope assembly by phosphorylation of BANF1, and participates in signalling required for Golgi fragmentation late in the G2 phase
  • mitotic kinases that play important roles in cell cycle, nuclear condensation, and transcription regulation
  • VRK1 and VRK2 are atypical active Ser-Thr kinases implicated in control of cell cycle entry, apoptosis and autophagy, and affect signalling by mitogen activated protein kinases (MAPK)
  • play crucial roles in germ cell development
  • required for telomere maintenance via phosphorylation of HNRNPA1, which regulates proteins associated with the telomere and telomerase RNA
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • with JUN (activates c-Jun dependent transcription, which is dependent on phosphorylation of Ser63 and Ser73)
  • critical link in the CCND1 gene expression pathway stimulated by Myc overexpression and regulator of CCND1 expression
  • COIL colocalizes and interacts with VRK1 in Cajal bodies, but not with the mutant VRK1)
  • H2AFY functions as a suppressor against VRK1 during interphase
  • H2AFY binds to VRK1 and sequesters it from histone H3 during interphase of the cell cycle
  • in resting cells plays an important role in the formation of ionizing radiation-induced foci that assemble on the TP53BP1 scaffold protein during the DNA damage response
  • evidence for the role of bivalent cations in structural stabilities of VRK1, VRK2, VRK3
  • VRK1 is the major kinase responsible for phosphorylation of BANF1
    • cell & other
    REGULATION
    ASSOCIATED DISORDERS
    corresponding disease(s) PCH1
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --low  
    has an impact on the proliferation and survival of cell lines derived from normal or malignant mammary tissue, and reduces their oncogenic and metastatic properties
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target might be a new target for development of inhibitors of cellular proliferation
    ANIMAL & CELL MODELS
  • mice deficient in the serine/threonine protein kinase Vrk1 are infertile due to a progressive loss of spermatogonia