LOCUS       NP_006287                508 aa            linear   PRI 07-APR-2024
DEFINITION  serine/threonine-protein kinase VRK2 isoform 1 [Homo sapiens].
ACCESSION   NP_006287
VERSION     NP_006287.2
DBSOURCE    REFSEQ: accession NM_006296.7
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (residues 1 to 508)
  AUTHORS   Puja,R., Dutta,S. and Bose,K.
  TITLE     Elucidating the interaction of C-terminal domain of
            Vaccinia-Related Kinase 2A (VRK2A) with B-cell lymphoma-extra Large
            (Bcl-xL) to decipher its anti-apoptotic role in cancer
  JOURNAL   Biochem J 480 (22), 1871-1885 (2023)
   PUBMED   37943248
  REMARK    GeneRIF: Elucidating the interaction of C-terminal domain of
            Vaccinia-Related Kinase 2A (VRK2A) with B-cell lymphoma-extra Large
            (Bcl-xL) to decipher its anti-apoptotic role in cancer.
REFERENCE   2  (residues 1 to 508)
  AUTHORS   Yin,M.Y., Guo,L., Zhao,L.J., Zhang,C., Liu,W.P., Zhang,C.Y.,
            Huo,J.H., Wang,L., Li,S.W., Zheng,C.B., Xiao,X., Li,M., Wang,C. and
            Chang,H.
  TITLE     Reduced Vrk2 expression is associated with higher risk of
            depression in humans and mediates depressive-like behaviors in mice
  JOURNAL   BMC Med 21 (1), 256 (2023)
   PUBMED   37452335
  REMARK    GeneRIF: Reduced Vrk2 expression is associated with higher risk of
            depression in humans and mediates depressive-like behaviors in
            mice.
            Publication Status: Online-Only
REFERENCE   3  (residues 1 to 508)
  AUTHORS   So,J., Mabe,N.W., Englinger,B., Chow,K.H., Moyer,S.M., Yerrum,S.,
            Trissal,M.C., Marques,J.G., Kwon,J.J., Shim,B., Pal,S.,
            Panditharatna,E., Quinn,T., Schaefer,D.A., Jeong,D., Mayhew,D.L.,
            Hwang,J., Beroukhim,R., Ligon,K.L., Stegmaier,K., Filbin,M.G. and
            Hahn,W.C.
  TITLE     VRK1 as a synthetic lethal target in VRK2 promoter-methylated
            cancers of the nervous system
  JOURNAL   JCI Insight 7 (19), e158755 (2022)
   PUBMED   36040810
  REMARK    GeneRIF: VRK1 as a synthetic lethal target in VRK2
            promoter-methylated cancers of the nervous system.
            Publication Status: Online-Only
REFERENCE   4  (residues 1 to 508)
  AUTHORS   Chen,J., Qiao,K., Zhang,C., Zhou,X., Du,Q., Deng,Y. and Cao,L.
  TITLE     VRK2 activates TNFalpha/NF-kappaB signaling by phosphorylating
            IKKbeta in pancreatic cancer
  JOURNAL   Int J Biol Sci 18 (3), 1288-1302 (2022)
   PUBMED   35173553
  REMARK    GeneRIF: VRK2 activates TNFalpha/NF-kappaB signaling by
            phosphorylating IKKbeta in pancreatic cancer.
            Publication Status: Online-Only
REFERENCE   5  (residues 1 to 508)
  AUTHORS   Blanco,S., Santos,C. and Lazo,P.A.
  TITLE     Vaccinia-related kinase 2 modulates the stress response to hypoxia
            mediated by TAK1
  JOURNAL   Mol Cell Biol 27 (20), 7273-7283 (2007)
   PUBMED   17709393
  REMARK    GeneRIF: Data show that TAK1 forms a stable complex with JIP1 and
            regulates the activation of JNK, which in turn determines the
            cellular stress response to hypoxia; this activation of
            TAK1-JIP1-JNK is suppressed by vaccinia-related kinase 2.
REFERENCE   6  (residues 1 to 508)
  AUTHORS   Li,L.Y., Liu,M.Y., Shih,H.M., Tsai,C.H. and Chen,J.Y.
  TITLE     Human cellular protein VRK2 interacts specifically with
            Epstein-Barr virus BHRF1, a homologue of Bcl-2, and enhances cell
            survival
  JOURNAL   J Gen Virol 87 (Pt 10), 2869-2878 (2006)
   PUBMED   16963744
  REMARK    GeneRIF: human VRK2 interacts specifically with EBV BHRF1 and that
            the interaction is involved in protecting cells from apoptosis
REFERENCE   7  (residues 1 to 508)
  AUTHORS   Blanco,S., Klimcakova,L., Vega,F.M. and Lazo,P.A.
  TITLE     The subcellular localization of vaccinia-related kinase-2 (VRK2)
            isoforms determines their different effect on p53 stability in
            tumour cell lines
  JOURNAL   FEBS J 273 (11), 2487-2504 (2006)
   PUBMED   16704422
  REMARK    GeneRIF: VRK2 induces p53 stabilization by post-translational
            modification, largely due to threonine 18 phosphorylation in tumor
            cell lines.
REFERENCE   8  (residues 1 to 508)
  AUTHORS   Nichols,R.J., Wiebe,M.S. and Traktman,P.
  TITLE     The vaccinia-related kinases phosphorylate the N' terminus of BAF,
            regulating its interaction with DNA and its retention in the
            nucleus
  JOURNAL   Mol Biol Cell 17 (5), 2451-2464 (2006)
   PUBMED   16495336
REFERENCE   9  (residues 1 to 508)
  AUTHORS   Nichols,R.J. and Traktman,P.
  TITLE     Characterization of three paralogous members of the Mammalian
            vaccinia related kinase family
  JOURNAL   J Biol Chem 279 (9), 7934-7946 (2004)
   PUBMED   14645249
REFERENCE   10 (residues 1 to 508)
  AUTHORS   Nezu,J., Oku,A., Jones,M.H. and Shimane,M.
  TITLE     Identification of two novel human putative serine/threonine
            kinases, VRK1 and VRK2, with structural similarity to vaccinia
            virus B1R kinase
  JOURNAL   Genomics 45 (2), 327-331 (1997)
   PUBMED   9344656
COMMENT     REVIEWED REFSEQ: This record has been curated by NCBI staff. The
            reference sequence was derived from BC027854.1 and AK223540.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            On Jul 26, 2005 this sequence version replaced NP_006287.1.
            
            Summary: This gene encodes a member of the vaccinia-related kinase
            (VRK) family of serine/threonine protein kinases. The encoded
            protein acts as an effector of signaling pathways that regulate
            apoptosis and tumor cell growth. Variants in this gene have been
            associated with schizophrenia. Alternative splicing results in
            multiple transcript variants that differ in their subcellular
            localization and biological activity. [provided by RefSeq, Jan
            2014].
            
            Transcript Variant: This variant (1) encodes the longest isoform
            (1). Variants 1, 2, 3, and 8 encode the same isoform (1, also known
            as VRK2A).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: BC027854.1, AK058199.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000340157.9/ ENSP00000342381.4
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..508
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="2"
                     /map="2p16.1"
     Protein         1..508
                     /product="serine/threonine-protein kinase VRK2 isoform 1"
                     /EC_number="2.7.11.1"
                     /note="serine/threonine-protein kinase VRK2; vaccinia
                     virus B1R-related kinase 2; vaccinia related kinase 2"
                     /calculated_mol_wt=58010
     Region          16..314
                     /region_name="STKc_VRK2"
                     /note="Catalytic domain of the Serine/Threonine protein
                     kinase, Vaccinia Related Kinase 2; cd14123"
                     /db_xref="CDD:271025"
     Site            order(35..39,43,59,61,101,121..124,127,129,166,168,
                     170..171,173,186,189,212..215)
                     /site_type="active"
                     /db_xref="CDD:271025"
     Site            order(35..39,43,59,61,101,121..124,127,166,168,170..171,
                     173,186)
                     /site_type="other"
                     /note="ATP binding site [chemical binding]"
                     /db_xref="CDD:271025"
     Site            order(39,127,129,166,168,170,189,212..215)
                     /site_type="other"
                     /note="polypeptide substrate binding site [polypeptide
                     binding]"
                     /db_xref="CDD:271025"
     Site            185..215
                     /site_type="other"
                     /note="activation loop (A-loop)"
                     /db_xref="CDD:271025"
     Site            336
                     /site_type="phosphorylation"
                     /note="Phosphothreonine.
                     /evidence=ECO:0007744|PubMed:18691976; propagated from
                     UniProtKB/Swiss-Prot (Q86Y07.3)"
     Region          397..508
                     /region_name="Interaction with MAP3K7.
                     /evidence=ECO:0000269|PubMed:17709393"
                     /note="propagated from UniProtKB/Swiss-Prot (Q86Y07.3)"
     Site            406
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (Q86Y07.3)"
     Site            487..507
                     /site_type="transmembrane region"
                     /note="propagated from UniProtKB/Swiss-Prot (Q86Y07.3)"
     CDS             1..508
                     /gene="VRK2"
                     /coded_by="NM_006296.7:69..1595"
                     /note="isoform 1 is encoded by transcript variant 1"
                     /db_xref="CCDS:CCDS1859.1"
                     /db_xref="GeneID:7444"
                     /db_xref="HGNC:HGNC:12719"
                     /db_xref="MIM:602169"
ORIGIN      
        1 mppkrnekyk lpipfpegkv lddmegnqwv lgkkigsggf gliylafptn kpekdarhvv
       61 kveyqengpl fselkfyqrv akkdcikkwi erkqldylgi plfygsglte fkgrsyrfmv
      121 merlgidlqk isgqngtfkk stvlqlgirm ldvleyihen eyvhgdikaa nlllgyknpd
      181 qvyladygls yrycpngnhk qyqenprkgh ngtieftsld ahkgvalsrr sdveilgycm
      241 lrwlcgklpw eqnlkdpvav qtaktnllde lpqsvlkwap sgsscceiaq flvcahslay
      301 dekpnyqalk kilnphgipl gpldfstkgq sinvhtpnsq kvdsqkaatk qvnkahnrli
      361 ekkvhsersa escatwkvqk eekliglmnn eaaqestrrr qkyqesqepl nevnsfpqki
      421 sytqfpnsfy ephqdftspd ifkksrspsw ykytstvstg itdlesstgl wptisqftls
      481 eetnadvyyy riiipvllml vflalffl
//
