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Protein

Serine/threonine-protein kinase VRK2

Gene

Vrk2

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 histone H3. Phosphorylates 'Thr-18' of p53/TP53, and thereby increases its stability and activity. 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. May also phosphorylate MAPK8IP1. 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 (By similarity).By similarity

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei61 – 611ATPPROSITE-ProRule annotation
Active sitei166 – 1661Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi35 – 439ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB-KW
  2. protein domain specific binding Source: MGI
  3. protein kinase binding Source: MGI
  4. protein serine/threonine kinase activity Source: MGI

GO - Biological processi

  1. cellular response to oxidative stress Source: UniProtKB
  2. endocytosis Source: GO_Central
  3. peptidyl-serine phosphorylation Source: GO_Central
  4. protein autophosphorylation Source: MGI
  5. protein phosphorylation Source: MGI
  6. regulation of cell shape Source: GO_Central
  7. regulation of interleukin-1-mediated signaling pathway Source: UniProtKB
  8. regulation of MAPK cascade Source: UniProtKB
  9. Wnt signaling pathway Source: GO_Central
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase VRK2 (EC:2.7.11.1)
Alternative name(s):
Vaccinia-related kinase 2
Gene namesi
Name:Vrk2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 11

Organism-specific databases

MGIiMGI:1917172. Vrk2.

Subcellular locationi

Cytoplasm 1 Publication. Endoplasmic reticulum membrane Curated; Single-pass type IV membrane protein Curated. Mitochondrion membrane Curated; Single-pass type IV membrane protein Curated

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transmembranei482 – 50221Helical; Anchor for type IV membrane proteinSequence AnalysisAdd
BLAST

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. endoplasmic reticulum Source: MGI
  3. endoplasmic reticulum membrane Source: UniProtKB
  4. integral component of membrane Source: UniProtKB-KW
  5. membrane Source: MGI
  6. mitochondrial membrane Source: UniProtKB
  7. nucleus Source: UniProtKB
  8. protein complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Endoplasmic reticulum, Membrane, Mitochondrion

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 503503Serine/threonine-protein kinase VRK2PRO_0000086807Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei336 – 3361PhosphothreonineBy similarity

Post-translational modificationi

Autophosphorylated.

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ8BN21.
PRIDEiQ8BN21.

PTM databases

PhosphoSiteiQ8BN21.

Expressioni

Tissue specificityi

Expressed in liver, kidney and muscle. Weakly expressed in thymus, bone marrow and spleen.1 Publication

Developmental stagei

Weakly expressed in embryo compared to VRK1 and VRK3. Expressed from E10.5 to E14 in developing liver and then decreases. It increases again from E17.5 and remains thereafter. Highly expressed in hematopoietic embryonic tissues from E10.5 to E14.5. Weakly expressed in the yolk-sac.1 Publication

Gene expression databases

BgeeiQ8BN21.
CleanExiMM_VRK2.
ExpressionAtlasiQ8BN21. baseline and differential.
GenevestigatoriQ8BN21.

Interactioni

Subunit structurei

Interacts with MAP3K7, MAP2K7, MAP2K1, KSR1, RAN and MAPK8IP1.By similarity

Protein-protein interaction databases

BioGridi213758. 1 interaction.

Structurei

3D structure databases

ProteinModelPortaliQ8BN21.
SMRiQ8BN21. Positions 15-330.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini29 – 313285Protein kinasePROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni392 – 503112Interaction with MAP3K7By similarityAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000119040.
HOVERGENiHBG007532.
InParanoidiQ8BN21.
KOiK08816.
OMAiHQDFTSP.
OrthoDBiEOG7KSX83.
PhylomeDBiQ8BN21.
TreeFamiTF106473.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: Q8BN21-1) [UniParc]FASTAAdd to Basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAPRRKEKYK LPVPLPEGKI LDDMEGNRWA LGKMIGSGGF GLIYLAFPTN
60 70 80 90 100
KPNKDARHVI KLEYQENGPL FSELKFYQRA AKRECIQKWI QQRKLDYLGI
110 120 130 140 150
PVFYGFGLTD FKGRSYRFMV MERLGIDLQK LLDQNGGFKK LTVLQLGIRM
160 170 180 190 200
LDVLEYIHEN EYVHGDIKAA NLLLDFTNPD RVYLADYGLS YRYCPNGNHK
210 220 230 240 250
QYQEDPRKGH NGTIEFTSLD AHKGVAPSRR SDVEILGYCM LHWLFGKLPW
260 270 280 290 300
EAKLDDPVAV QTAKTNLLDE LPESVLKWAP SGSSCSELVK YLMYVHNLAY
310 320 330 340 350
DDKPDYQKLK KILNPDGVPL GPLEFSTKVQ SVHVRTPAQQ KVDSPKATRK
360 370 380 390 400
PANEFPAKFP KKVHRETRAR QREEQEDSQP TMLQSRPAAP ENSRTRKIHE
410 420 430 440 450
YSDIFSEMQS LQQTPSYMSF QGSYCKPYLD CTRRDPIRKP RSLPRYRHTP
460 470 480 490 500
TGNLGVTDLE SSPRFWPAIF QLTLSEETKA DVYYYGITIF CLLIFVFLAL

YFL
Length:503
Mass (Da):58,119
Last modified:October 10, 2003 - v2
Checksum:i6F29E3E412ECB221
GO
Isoform 2 (identifier: Q8BN21-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     342-390: Missing.

Note: No experimental confirmation available.

Show »
Length:454
Mass (Da):52,493
Checksum:i4AAD5406E8214578
GO
Isoform 3 (identifier: Q8BN21-3) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     151-163: LDVLEYIHENEYV → VSLRDLTGDLLDI
     164-503: Missing.

Note: No experimental confirmation available.

Show »
Length:163
Mass (Da):18,844
Checksum:i43B728DB7DC2FE52
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti33 – 331K → R in AAN64922. (PubMed:12417526)Curated
Sequence conflicti226 – 2261A → P in BAB28393. (PubMed:16141072)Curated
Sequence conflicti319 – 3191P → L in BAE32620. (PubMed:16141072)Curated
Sequence conflicti319 – 3191P → L in AAH13520. (PubMed:15489334)Curated
Sequence conflicti333 – 3331H → R in BAE32620. (PubMed:16141072)Curated
Sequence conflicti333 – 3331H → R in AAH13520. (PubMed:15489334)Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei151 – 16313LDVLE…ENEYV → VSLRDLTGDLLDI in isoform 3. 1 PublicationVSP_008541Add
BLAST
Alternative sequencei164 – 503340Missing in isoform 3. 1 PublicationVSP_008542Add
BLAST
Alternative sequencei342 – 39049Missing in isoform 2. 1 PublicationVSP_008543Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF513620 mRNA. Translation: AAN64922.1.
AK012664 mRNA. Translation: BAB28393.1.
AK053297 mRNA. Translation: BAC35335.1.
AK154485 mRNA. Translation: BAE32620.1.
AL929272, AC083815 Genomic DNA. Translation: CAI52021.1.
BC013520 mRNA. Translation: AAH13520.1.
CCDSiCCDS24486.1. [Q8BN21-1]
RefSeqiNP_001239376.1. NM_001252447.1. [Q8BN21-2]
NP_081536.2. NM_027260.3. [Q8BN21-1]
XP_006514864.1. XM_006514801.1. [Q8BN21-1]
XP_006514865.1. XM_006514802.1. [Q8BN21-1]
UniGeneiMm.285351.

Genome annotation databases

EnsembliENSMUST00000078362; ENSMUSP00000077471; ENSMUSG00000064090. [Q8BN21-1]
ENSMUST00000109504; ENSMUSP00000105130; ENSMUSG00000064090. [Q8BN21-1]
GeneIDi69922.
KEGGimmu:69922.
UCSCiuc007igf.2. mouse. [Q8BN21-1]
uc007igg.2. mouse. [Q8BN21-3]
uc011xsk.2. mouse. [Q8BN21-2]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF513620 mRNA. Translation: AAN64922.1.
AK012664 mRNA. Translation: BAB28393.1.
AK053297 mRNA. Translation: BAC35335.1.
AK154485 mRNA. Translation: BAE32620.1.
AL929272, AC083815 Genomic DNA. Translation: CAI52021.1.
BC013520 mRNA. Translation: AAH13520.1.
CCDSiCCDS24486.1. [Q8BN21-1]
RefSeqiNP_001239376.1. NM_001252447.1. [Q8BN21-2]
NP_081536.2. NM_027260.3. [Q8BN21-1]
XP_006514864.1. XM_006514801.1. [Q8BN21-1]
XP_006514865.1. XM_006514802.1. [Q8BN21-1]
UniGeneiMm.285351.

3D structure databases

ProteinModelPortaliQ8BN21.
SMRiQ8BN21. Positions 15-330.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi213758. 1 interaction.

PTM databases

PhosphoSiteiQ8BN21.

Proteomic databases

MaxQBiQ8BN21.
PRIDEiQ8BN21.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000078362; ENSMUSP00000077471; ENSMUSG00000064090. [Q8BN21-1]
ENSMUST00000109504; ENSMUSP00000105130; ENSMUSG00000064090. [Q8BN21-1]
GeneIDi69922.
KEGGimmu:69922.
UCSCiuc007igf.2. mouse. [Q8BN21-1]
uc007igg.2. mouse. [Q8BN21-3]
uc011xsk.2. mouse. [Q8BN21-2]

Organism-specific databases

CTDi7444.
MGIiMGI:1917172. Vrk2.

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00760000119040.
HOVERGENiHBG007532.
InParanoidiQ8BN21.
KOiK08816.
OMAiHQDFTSP.
OrthoDBiEOG7KSX83.
PhylomeDBiQ8BN21.
TreeFamiTF106473.

Miscellaneous databases

NextBioi330615.
PROiQ8BN21.
SOURCEiSearch...

Gene expression databases

BgeeiQ8BN21.
CleanExiMM_VRK2.
ExpressionAtlasiQ8BN21. baseline and differential.
GenevestigatoriQ8BN21.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "A novel gene, Pog, is necessary for primordial germ cell proliferation in the mouse and underlies the germ cell deficient mutation, gcd."
    Agoulnik A.I., Lu B., Zhu Q., Truong C., Ty M.T., Arango N., Chada K.K., Bishop C.E.
    Hum. Mol. Genet. 11:3047-3053(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    Strain: C57BL/6.
  2. "The transcriptional landscape of the mammalian genome."
    Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.
    , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.
    Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
    Strain: C57BL/6J and NOD.
    Tissue: Dendritic cell, Embryo, Eye and Spleen.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Tissue: Kidney.
  5. "Expression of the VRK (vaccinia-related kinase) gene family of p53 regulators in murine hematopoietic development."
    Vega F.M., Gonzalo P., Gaspar M.L., Lazo P.A.
    FEBS Lett. 544:176-180(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE.
  6. "Characterization of three paralogous members of the Mammalian vaccinia related kinase family."
    Nichols R.J., Traktman P.
    J. Biol. Chem. 279:7934-7946(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, AUTOPHOSPHORYLATION.

Entry informationi

Entry nameiVRK2_MOUSE
AccessioniPrimary (citable) accession number: Q8BN21
Secondary accession number(s): Q3U415
, Q5F1Z5, Q5SP88, Q8BPU8, Q8CJ46, Q91WS1, Q9CZF9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 10, 2003
Last sequence update: October 10, 2003
Last modified: February 4, 2015
This is version 116 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

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 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.