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Protein

Serine/threonine-protein kinase VRK1

Gene

VRK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Enzyme 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

  • ATP binding Source: UniProtKB-KW
  • histone kinase activity (H3-S10 specific) Source: UniProtKB
  • histone kinase activity (H3-T3 specific) Source: UniProtKB
  • nucleosomal histone binding Source: UniProtKB
  • protein kinase activity Source: UniProtKB
  • protein kinase binding Source: MGI
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • cell division Source: UniProtKB-KW
  • Golgi disassembly Source: UniProtKB
  • histone H3-S10 phosphorylation Source: UniProtKB
  • histone H3-T3 phosphorylation Source: UniProtKB
  • mitotic nuclear division Source: UniProtKB-KW
  • mitotic nuclear envelope disassembly Source: Reactome
  • mitotic nuclear envelope reassembly Source: Reactome
  • protein autophosphorylation Source: UniProtKB
  • protein phosphorylation Source: UniProtKB
  • regulation of cell shape Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Cell cycle, Cell division, Mitosis

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Enzyme and pathway databases

BioCyciZFISH:HS02141-MONOMER.
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

HGNCiHGNC:12718. VRK1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • cytosol Source: Reactome
  • Golgi stack Source: UniProtKB
  • nucleolus Source: HPA
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • spindle Source: UniProtKB-SubCell
Complete GO annotation...

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.
GuidetoPHARMACOLOGYi2275.

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
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

Phosphoprotein

Proteomic databases

EPDiQ99986.
MaxQBiQ99986.
PaxDbiQ99986.
PeptideAtlasiQ99986.
PRIDEiQ99986.

PTM databases

iPTMnetiQ99986.
PhosphoSitePlusiQ99986.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiENSG00000100749.
CleanExiHS_VRK1.
ExpressionAtlasiQ99986. baseline and differential.
GenevisibleiQ99986. HS.

Organism-specific databases

HPAiHPA000660.
HPA017929.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
ATF2P153365EBI-1769146,EBI-1170906
COILP384329EBI-1769146,EBI-945751
H2AFXP161043EBI-1769146,EBI-494830
JUNP054125EBI-1769146,EBI-852823
NBNO6093413EBI-1769146,EBI-494844
PLK3Q9H4B412EBI-1769146,EBI-751877
RANP6282612EBI-1769146,EBI-286642
RNF8O760642EBI-1769146,EBI-373337
SOX2P4843114EBI-1769146,EBI-6124081
TP53P046379EBI-1769146,EBI-366083
TP53BP1Q128888EBI-1769146,EBI-396540

GO - Molecular functioni

  • nucleosomal histone binding Source: UniProtKB
  • protein kinase binding Source: MGI

Protein-protein interaction databases

BioGridi113282. 31 interactors.
IntActiQ99986. 18 interactors.
MINTiMINT-3060185.
STRINGi9606.ENSP00000216639.

Chemistry databases

BindingDBiQ99986.

Structurei

Secondary structure

1396
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni2 – 4Combined sources3
Beta strandi11 – 13Combined sources3
Beta strandi22 – 24Combined sources3
Beta strandi28 – 30Combined sources3
Beta strandi36 – 42Combined sources7
Beta strandi46 – 49Combined sources4
Beta strandi50 – 56Combined sources7
Beta strandi59 – 61Combined sources3
Beta strandi67 – 74Combined sources8
Helixi78 – 90Combined sources13
Helixi93 – 102Combined sources10
Beta strandi113 – 121Combined sources9
Beta strandi124 – 132Combined sources9
Beta strandi134 – 137Combined sources4
Helixi138 – 144Combined sources7
Turni145 – 147Combined sources3
Helixi151 – 170Combined sources20
Helixi180 – 182Combined sources3
Beta strandi183 – 188Combined sources6
Beta strandi193 – 195Combined sources3
Helixi198 – 200Combined sources3
Beta strandi202 – 205Combined sources4
Helixi206 – 208Combined sources3
Turni225 – 227Combined sources3
Helixi230 – 233Combined sources4
Helixi240 – 256Combined sources17
Helixi262 – 264Combined sources3
Helixi268 – 280Combined sources13
Helixi282 – 289Combined sources8
Beta strandi291 – 294Combined sources4
Helixi297 – 307Combined sources11
Beta strandi311 – 313Combined sources3
Helixi317 – 330Combined sources14
Beta strandi355 – 357Combined sources3

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[»]
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

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1164. Eukaryota.
ENOG410XPGP. LUCA.
GeneTreeiENSGT00850000132311.
HOGENOMiHOG000069991.
HOVERGENiHBG007532.
InParanoidiQ99986.
KOiK08816.
OMAiAYRYCPD.
OrthoDBiEOG091G05V5.
PhylomeDBiQ99986.
TreeFamiTF106473.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

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.

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[»]
ProteinModelPortaliQ99986.
SMRiQ99986.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113282. 31 interactors.
IntActiQ99986. 18 interactors.
MINTiMINT-3060185.
STRINGi9606.ENSP00000216639.

Chemistry databases

BindingDBiQ99986.
ChEMBLiCHEMBL1293199.
GuidetoPHARMACOLOGYi2275.

PTM databases

iPTMnetiQ99986.
PhosphoSitePlusiQ99986.

Polymorphism and mutation databases

BioMutaiVRK1.
DMDMi45593726.

Proteomic databases

EPDiQ99986.
MaxQBiQ99986.
PaxDbiQ99986.
PeptideAtlasiQ99986.
PRIDEiQ99986.

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.
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.
GeneTreeiENSGT00850000132311.
HOGENOMiHOG000069991.
HOVERGENiHBG007532.
InParanoidiQ99986.
KOiK08816.
OMAiAYRYCPD.
OrthoDBiEOG091G05V5.
PhylomeDBiQ99986.
TreeFamiTF106473.

Enzyme and pathway databases

BioCyciZFISH:HS02141-MONOMER.
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.
PROiQ99986.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000100749.
CleanExiHS_VRK1.
ExpressionAtlasiQ99986. baseline and differential.
GenevisibleiQ99986. HS.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiVRK1_HUMAN
AccessioniPrimary (citable) accession number: Q99986
Secondary accession number(s): Q3SYL2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 10, 2003
Last sequence update: May 1, 1997
Last modified: November 2, 2016
This is version 164 of the entry and version 1 of the sequence. [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

Documents

  1. Human chromosome 14
    Human chromosome 14: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.