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Q8BN21

- VRK2_MOUSE

UniProt

Q8BN21 - VRK2_MOUSE

Protein

Serine/threonine-protein kinase VRK2

Gene

Vrk2

Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 112 (01 Oct 2014)
      Sequence version 2 (10 Oct 2003)
      Previous versions | rss
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    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 serine/threonine kinase activity Source: MGI

    GO - Biological processi

    1. cellular response to oxidative stress Source: UniProtKB
    2. protein autophosphorylation Source: MGI
    3. protein phosphorylation Source: MGI
    4. regulation of interleukin-1-mediated signaling pathway Source: UniProtKB
    5. regulation of MAPK cascade Source: UniProtKB

    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

    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

    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

    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

    ArrayExpressiQ8BN21.
    BgeeiQ8BN21.
    CleanExiMM_VRK2.
    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...

    Transmembrane

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

    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.
    GeneTreeiENSGT00730000110259.
    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

    MAPRRKEKYK LPVPLPEGKI LDDMEGNRWA LGKMIGSGGF GLIYLAFPTN    50
    KPNKDARHVI KLEYQENGPL FSELKFYQRA AKRECIQKWI QQRKLDYLGI 100
    PVFYGFGLTD FKGRSYRFMV MERLGIDLQK LLDQNGGFKK LTVLQLGIRM 150
    LDVLEYIHEN EYVHGDIKAA NLLLDFTNPD RVYLADYGLS YRYCPNGNHK 200
    QYQEDPRKGH NGTIEFTSLD AHKGVAPSRR SDVEILGYCM LHWLFGKLPW 250
    EAKLDDPVAV QTAKTNLLDE LPESVLKWAP SGSSCSELVK YLMYVHNLAY 300
    DDKPDYQKLK KILNPDGVPL GPLEFSTKVQ SVHVRTPAQQ KVDSPKATRK 350
    PANEFPAKFP KKVHRETRAR QREEQEDSQP TMLQSRPAAP ENSRTRKIHE 400
    YSDIFSEMQS LQQTPSYMSF QGSYCKPYLD CTRRDPIRKP RSLPRYRHTP 450
    TGNLGVTDLE SSPRFWPAIF QLTLSEETKA DVYYYGITIF CLLIFVFLAL 500
    YFL 503
    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:
    EMBL
    GenBank
    DDBJ
    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:
    EMBL
    GenBank
    DDBJ
    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 .
    CCDSi CCDS24486.1. [Q8BN21-1 ]
    RefSeqi NP_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 ]
    UniGenei Mm.285351.

    3D structure databases

    ProteinModelPortali Q8BN21.
    SMRi Q8BN21. Positions 15-330.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 213758. 1 interaction.

    PTM databases

    PhosphoSitei Q8BN21.

    Proteomic databases

    PRIDEi Q8BN21.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENSMUST00000078362 ; ENSMUSP00000077471 ; ENSMUSG00000064090 . [Q8BN21-1 ]
    ENSMUST00000109504 ; ENSMUSP00000105130 ; ENSMUSG00000064090 . [Q8BN21-1 ]
    GeneIDi 69922.
    KEGGi mmu:69922.
    UCSCi uc007igf.2. mouse. [Q8BN21-1 ]
    uc007igg.2. mouse. [Q8BN21-3 ]
    uc011xsk.2. mouse. [Q8BN21-2 ]

    Organism-specific databases

    CTDi 7444.
    MGIi MGI:1917172. Vrk2.

    Phylogenomic databases

    eggNOGi COG0515.
    GeneTreei ENSGT00730000110259.
    HOVERGENi HBG007532.
    InParanoidi Q8BN21.
    KOi K08816.
    OMAi HQDFTSP.
    OrthoDBi EOG7KSX83.
    PhylomeDBi Q8BN21.
    TreeFami TF106473.

    Miscellaneous databases

    NextBioi 330615.
    PROi Q8BN21.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q8BN21.
    Bgeei Q8BN21.
    CleanExi MM_VRK2.
    Genevestigatori Q8BN21.

    Family and domain databases

    InterProi IPR011009. Kinase-like_dom.
    IPR000719. Prot_kinase_dom.
    IPR008271. Ser/Thr_kinase_AS.
    [Graphical view ]
    Pfami PF00069. Pkinase. 1 hit.
    [Graphical view ]
    SUPFAMi SSF56112. SSF56112. 1 hit.
    PROSITEi PS50011. PROTEIN_KINASE_DOM. 1 hit.
    PS00108. PROTEIN_KINASE_ST. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    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: October 1, 2014
    This is version 112 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