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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

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

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003384 13 - 1720 NP_003375 - 396 - 2008 18713830

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive salivary gland       highly Nervous brain hindbrain cerebellum   highly Urinary bladder       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone 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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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