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Protein

Serine/threonine-protein kinase VRK1

Gene

VRK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Serine/threonine kinase involved in Golgi disassembly during the cell cycle: following phosphorylation by PLK3 during mitosis, required to induce Golgi fragmentation. Acts by mediating phosphorylation of downstream target protein. Phosphorylates 'Thr-18' of p53/TP53 and may thereby prevent the interaction between p53/TP53 and MDM2. Phosphorylates casein and histone H3. Phosphorylates BANF1: disrupts its ability to bind DNA, reduces its binding to LEM domain-containing proteins and causes its relocalization from the nucleus to the cytoplasm. Phosphorylates ATF2 which activates its transcriptional activity.6 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Activity regulationi

Active in presence of Mn2+, Mg2+ and Zn2+, but is not functional with Ca2+ or Cu2+. Has a higher affinity for Mn2+ than for Mg2+. RAN inhibits its autophosphorylation and its ability to phosphorylate histone H3.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei71ATPPROSITE-ProRule annotation1
Active sitei177Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi43 – 51ATPPROSITE-ProRule annotation9

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processCell cycle, Cell division, Mitosis
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-2993913 Clearance of Nuclear Envelope Membranes from Chromatin
R-HSA-2995383 Initiation of Nuclear Envelope Reformation
SignaLinkiQ99986
SIGNORiQ99986

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase VRK1 (EC:2.7.11.1)
Alternative name(s):
Vaccinia-related kinase 1
Gene namesi
Name:VRK1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 14

Organism-specific databases

EuPathDBiHostDB:ENSG00000100749.7
HGNCiHGNC:12718 VRK1
MIMi602168 gene
neXtProtiNX_Q99986

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Nucleus

Pathology & Biotechi

Involvement in diseasei

Pontocerebellar hypoplasia 1A (PCH1A)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by an abnormally small cerebellum and brainstem, central and peripheral motor dysfunction from birth, gliosis and spinal cord anterior horn cells degeneration resembling infantile spinal muscular atrophy. Additional features include muscle hypotonia, congenital contractures and respiratory insufficiency that is evident at birth.
See also OMIM:607596

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi14S → A: Does not abolish autophosphorylation. 1 Publication1
Mutagenesisi102T → A: Does not abolish autophosphorylation. 1 Publication1
Mutagenesisi125S → A: Does not abolish autophosphorylation. 1 Publication1
Mutagenesisi150S → A: Does not abolish autophosphorylation. 1 Publication1
Mutagenesisi158S → A: Does not abolish autophosphorylation. 1 Publication1
Mutagenesisi179K → A: Does not affect phosphorylation at S-342. 1 Publication1
Mutagenesisi239S → A: Does not abolish autophosphorylation. 1 Publication1
Mutagenesisi305T → A: Does not abolish autophosphorylation. 1 Publication1
Mutagenesisi312T → A: Does not abolish autophosphorylation. 1 Publication1
Mutagenesisi342S → A: Abolishes phosphorylation by PLK3 and induction of Golgi fragmentation during mitosis. Strongly reduced autophosphorylation. 2 Publications1
Mutagenesisi353T → A: Strongly reduced autophosphorylation. 1 Publication1
Mutagenesisi355T → A: Does not abolish autophosphorylation. 1 Publication1
Mutagenesisi390T → A: Does not abolish autophosphorylation. 1 Publication1

Keywords - Diseasei

Neurodegeneration

Organism-specific databases

DisGeNETi7443
MalaCardsiVRK1
MIMi607596 phenotype
OpenTargetsiENSG00000100749
Orphaneti2254 Pontocerebellar hypoplasia type 1
PharmGKBiPA37330

Chemistry databases

ChEMBLiCHEMBL1293199

Polymorphism and mutation databases

BioMutaiVRK1
DMDMi45593726

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000868031 – 396Serine/threonine-protein kinase VRK1Add BLAST396

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki71Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei342Phosphoserine; by PLK3Combined sources1 Publication1
Modified residuei355Phosphothreonine; by autocatalysis1 Publication1
Modified residuei376PhosphoserineCombined sources1
Modified residuei378PhosphothreonineCombined sources1

Post-translational modificationi

Autophosphorylated at various serine and threonine residues. Autophosphorylation does not impair its ability to phosphorylate p53/TP53. Phosphorylation by PLK3 leads to induction of Golgi fragmentation during mitosis.3 Publications

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ99986
MaxQBiQ99986
PaxDbiQ99986
PeptideAtlasiQ99986
PRIDEiQ99986
ProteomicsDBi78563

PTM databases

iPTMnetiQ99986
PhosphoSitePlusiQ99986

Expressioni

Tissue specificityi

Widely expressed. Highly expressed in fetal liver, testis and thymus.1 Publication

Gene expression databases

BgeeiENSG00000100749 Expressed in 222 organ(s), highest expression level in bone marrow
CleanExiHS_VRK1
ExpressionAtlasiQ99986 baseline and differential
GenevisibleiQ99986 HS

Organism-specific databases

HPAiHPA000660
HPA017929

Interactioni

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi113282, 36 interactors
IntActiQ99986, 20 interactors
MINTiQ99986
STRINGi9606.ENSP00000216639

Chemistry databases

BindingDBiQ99986

Structurei

Secondary structure

1396
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ99986
SMRiQ99986
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ99986

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini37 – 317Protein kinasePROSITE-ProRule annotationAdd BLAST281

Sequence similaritiesi

Phylogenomic databases

eggNOGiKOG1164 Eukaryota
ENOG410XPGP LUCA
GeneTreeiENSGT00920000148988
HOGENOMiHOG000069991
HOVERGENiHBG007532
InParanoidiQ99986
KOiK08816
OMAiYMRAAKP
OrthoDBiEOG091G05V5
PhylomeDBiQ99986
TreeFamiTF106473

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit

Sequence (1+)i

Sequence statusi: Complete.

This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.iShow all

Q99986-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MPRVKAAQAG RQSSAKRHLA EQFAVGEIIT DMAKKEWKVG LPIGQGGFGC
60 70 80 90 100
IYLADMNSSE SVGSDAPCVV KVEPSDNGPL FTELKFYQRA AKPEQIQKWI
110 120 130 140 150
RTRKLKYLGV PKYWGSGLHD KNGKSYRFMI MDRFGSDLQK IYEANAKRFS
160 170 180 190 200
RKTVLQLSLR ILDILEYIHE HEYVHGDIKA SNLLLNYKNP DQVYLVDYGL
210 220 230 240 250
AYRYCPEGVH KEYKEDPKRC HDGTIEFTSI DAHNGVAPSR RGDLEILGYC
260 270 280 290 300
MIQWLTGHLP WEDNLKDPKY VRDSKIRYRE NIASLMDKCF PEKNKPGEIA
310 320 330 340 350
KYMETVKLLD YTEKPLYENL RDILLQGLKA IGSKDDGKLD LSVVENGGLK
360 370 380 390
AKTITKKRKK EIEESKEPGV EDTEWSNTQT EEAIQTRSRT RKRVQK
Length:396
Mass (Da):45,476
Last modified:May 1, 1997 - v1
Checksum:i5640C624BF059949
GO

Computationally mapped potential isoform sequencesi

There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
H0YJJ9H0YJJ9_HUMAN
Serine/threonine-protein kinase VRK...
VRK1
176Annotation score:
H0YJ50H0YJ50_HUMAN
Serine/threonine-protein kinase VRK...
VRK1
232Annotation score:
H0YJF7H0YJF7_HUMAN
Serine/threonine-protein kinase VRK...
VRK1
65Annotation score:

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB000449 mRNA Translation: BAA19108.1
BC103761 mRNA Translation: AAI03762.1
BC112075 mRNA Translation: AAI12076.1
BC113510 mRNA Translation: AAI13511.1
CCDSiCCDS9947.1
RefSeqiNP_003375.1, NM_003384.2
UniGeneiHs.422662

Genome annotation databases

EnsembliENST00000216639; ENSP00000216639; ENSG00000100749
GeneIDi7443
KEGGihsa:7443
UCSCiuc001yft.4 human

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB000449 mRNA Translation: BAA19108.1
BC103761 mRNA Translation: AAI03762.1
BC112075 mRNA Translation: AAI12076.1
BC113510 mRNA Translation: AAI13511.1
CCDSiCCDS9947.1
RefSeqiNP_003375.1, NM_003384.2
UniGeneiHs.422662

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KTYNMR-A1-360[»]
2KULNMR-A1-360[»]
2LAVNMR-A1-361[»]
2RSVNMR-A1-396[»]
3OP5X-ray2.40A/B/C/D3-364[»]
5UKFX-ray2.40A/B/C/D3-364[»]
5UVFX-ray2.00A/B/C/D3-364[»]
6BP0X-ray1.90A/B/C/D3-364[»]
6BRUX-ray1.80A/B/C/D3-364[»]
6BTWX-ray1.90A/B/C/D3-364[»]
6BU6X-ray1.80A/B/C/D3-364[»]
6CFMX-ray2.45A/B/C/D3-364[»]
6CMMX-ray2.10A/B/C/D3-364[»]
6CNXX-ray2.00A/B/C/D3-364[»]
6CQHX-ray2.15A/B/C/D3-364[»]
6CSWX-ray2.25A/B/C/D3-364[»]
6DD4X-ray2.10A/B/C/D3-364[»]
ProteinModelPortaliQ99986
SMRiQ99986
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113282, 36 interactors
IntActiQ99986, 20 interactors
MINTiQ99986
STRINGi9606.ENSP00000216639

Chemistry databases

BindingDBiQ99986
ChEMBLiCHEMBL1293199

PTM databases

iPTMnetiQ99986
PhosphoSitePlusiQ99986

Polymorphism and mutation databases

BioMutaiVRK1
DMDMi45593726

Proteomic databases

EPDiQ99986
MaxQBiQ99986
PaxDbiQ99986
PeptideAtlasiQ99986
PRIDEiQ99986
ProteomicsDBi78563

Protocols and materials databases

DNASUi7443
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000216639; ENSP00000216639; ENSG00000100749
GeneIDi7443
KEGGihsa:7443
UCSCiuc001yft.4 human

Organism-specific databases

CTDi7443
DisGeNETi7443
EuPathDBiHostDB:ENSG00000100749.7
GeneCardsiVRK1
HGNCiHGNC:12718 VRK1
HPAiHPA000660
HPA017929
MalaCardsiVRK1
MIMi602168 gene
607596 phenotype
neXtProtiNX_Q99986
OpenTargetsiENSG00000100749
Orphaneti2254 Pontocerebellar hypoplasia type 1
PharmGKBiPA37330
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1164 Eukaryota
ENOG410XPGP LUCA
GeneTreeiENSGT00920000148988
HOGENOMiHOG000069991
HOVERGENiHBG007532
InParanoidiQ99986
KOiK08816
OMAiYMRAAKP
OrthoDBiEOG091G05V5
PhylomeDBiQ99986
TreeFamiTF106473

Enzyme and pathway databases

ReactomeiR-HSA-2993913 Clearance of Nuclear Envelope Membranes from Chromatin
R-HSA-2995383 Initiation of Nuclear Envelope Reformation
SignaLinkiQ99986
SIGNORiQ99986

Miscellaneous databases

ChiTaRSiVRK1 human
EvolutionaryTraceiQ99986
GeneWikiiVRK1
GenomeRNAii7443
PROiPR:Q99986
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100749 Expressed in 222 organ(s), highest expression level in bone marrow
CleanExiHS_VRK1
ExpressionAtlasiQ99986 baseline and differential
GenevisibleiQ99986 HS

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR008271 Ser/Thr_kinase_AS
PfamiView protein in Pfam
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS00108 PROTEIN_KINASE_ST, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiVRK1_HUMAN
AccessioniPrimary (citable) accession number: Q99986
Secondary accession number(s): Q3SYL2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: October 10, 2003
Last sequence update: May 1, 1997
Last modified: September 12, 2018
This is version 181 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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