LOCUS       NP_003375                396 aa            linear   PRI 28-APR-2025
DEFINITION  serine/threonine-protein kinase VRK1 isoform 1 [Homo sapiens].
ACCESSION   NP_003375
VERSION     NP_003375.1
DBSOURCE    REFSEQ: accession NM_003384.3
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 396)
  AUTHORS   Oliveira,D., Assoni,A.F., Alves,L.M., Sakugawa,A., Melo,U.S., Teles
            E Silva,A.L., Sertie,A.L., Caires,L.C., Goulart,E., Ghirotto,B.,
            Carvalho,V.M., Ferrari,M.R. and Zatz,M.
  TITLE     ALS-associated VRK1 R321C mutation causes proteostatic imbalance
            and mitochondrial defects in iPSC-derived motor neurons
  JOURNAL   Neurobiol Dis 198, 106540 (2024)
   PUBMED   38806131
  REMARK    GeneRIF: ALS-associated VRK1 R321C mutation causes proteostatic
            imbalance and mitochondrial defects in iPSC-derived motor neurons.
REFERENCE   2  (residues 1 to 396)
  AUTHORS   Navarro-Carrasco,E., Monte-Serrano,E., Campos-Diaz,A., Rolfs,F., de
            Goeij-de Haas,R., Pham,T.V., Piersma,S.R., Gonzalez-Alonso,P.,
            Jimenez,C.R. and Lazo,P.A.
  TITLE     VRK1 Regulates Sensitivity to Oxidative Stress by Altering Histone
            Epigenetic Modifications and the Nuclear Phosphoproteome in Tumor
            Cells
  JOURNAL   Int J Mol Sci 25 (9), 4874 (2024)
   PUBMED   38732093
  REMARK    GeneRIF: VRK1 Regulates Sensitivity to Oxidative Stress by Altering
            Histone Epigenetic Modifications and the Nuclear Phosphoproteome in
            Tumor Cells.
            Publication Status: Online-Only
REFERENCE   3  (residues 1 to 396)
  AUTHORS   Fan,Z., Wang,X., Cheng,H. and Pan,M.
  TITLE     VRK1 promotes DNA-induced type I interferon production
  JOURNAL   Mol Biol Rep 51 (1), 453 (2024)
   PUBMED   38536553
  REMARK    GeneRIF: VRK1 promotes DNA-induced type I interferon production.
            Publication Status: Online-Only
REFERENCE   4  (residues 1 to 396)
  AUTHORS   Navarro-Carrasco,E., Campos-Diaz,A., Monte-Serrano,E., Rolfs,F., de
            Goeij-de Haas,R., Pham,T.V., Piersma,S.R., Jimenez,C.R. and
            Lazo,P.A.
  TITLE     Loss of VRK1 alters the nuclear phosphoproteome in the DNA damage
            response to doxorubicin
  JOURNAL   Chem Biol Interact 391, 110908 (2024)
   PUBMED   38367682
  REMARK    GeneRIF: Loss of VRK1 alters the nuclear phosphoproteome in the DNA
            damage response to doxorubicin.
REFERENCE   5  (residues 1 to 396)
  AUTHORS   Du,N., Zhang,B. and Zhang,Y.
  TITLE     Downregulation of VRK1 Inhibits Progression of Lung Squamous Cell
            Carcinoma through DNA Damage
  JOURNAL   Can Respir J 2023, 4533504 (2023)
   PUBMED   37547297
  REMARK    GeneRIF: Downregulation of VRK1 Inhibits Progression of Lung
            Squamous Cell Carcinoma through DNA Damage.
            Publication Status: Online-Only
REFERENCE   6  (residues 1 to 396)
  AUTHORS   Latonen,L., Taya,Y. and Laiho,M.
  TITLE     UV-radiation induces dose-dependent regulation of p53 response and
            modulates p53-HDM2 interaction in human fibroblasts
  JOURNAL   Oncogene 20 (46), 6784-6793 (2001)
   PUBMED   11709713
  REMARK    Erratum:[Oncogene 2001 Dec 6;20(56):8165]
REFERENCE   7  (residues 1 to 396)
  AUTHORS   Lopez-Borges,S. and Lazo,P.A.
  TITLE     The human vaccinia-related kinase 1 (VRK1) phosphorylates
            threonine-18 within the mdm-2 binding site of the p53 tumour
            suppressor protein
  JOURNAL   Oncogene 19 (32), 3656-3664 (2000)
   PUBMED   10951572
REFERENCE   8  (residues 1 to 396)
  AUTHORS   Sayed,M., Kim,S.O., Salh,B.S., Issinger,O.G. and Pelech,S.L.
  TITLE     Stress-induced activation of protein kinase CK2 by direct
            interaction with p38 mitogen-activated protein kinase
  JOURNAL   J Biol Chem 275 (22), 16569-16573 (2000)
   PUBMED   10747897
REFERENCE   9  (residues 1 to 396)
  AUTHORS   Sugimoto,J., Yamauchi,T., Hatakeyama,T. and Isobe,M.
  TITLE     Isolation and mapping of a polymorphic CA repeat sequence at the
            human VRK1 locus
  JOURNAL   J Hum Genet 44 (2), 133-134 (1999)
   PUBMED   10083742
REFERENCE   10 (residues 1 to 396)
  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 BU535261.1, AL133168.6 and
            CA436761.1.
            This sequence is a reference standard in the RefSeqGene project.
            
            Summary: This gene encodes a member of the vaccinia-related kinase
            (VRK) family of serine/threonine protein kinases. This gene is
            widely expressed in human tissues and has increased expression in
            actively dividing cells, such as those in testis, thymus, fetal
            liver, and carcinomas. Its protein localizes to the nucleus and has
            been shown to promote the stability and nuclear accumulation of a
            transcriptionally active p53 molecule and, in vitro, to
            phosphorylate Thr18 of p53 and reduce p53 ubiquitination. This
            gene, therefore, may regulate cell proliferation. This protein also
            phosphorylates histone, casein, and the transcription factors ATF2
            (activating transcription factor 2) and c-JUN. [provided by RefSeq,
            Jul 2008].
            
            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 :: BC103761.1, SRR1803611.253760.1
                                           [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMEA1965299, SAMEA1966682
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000216639.8/ ENSP00000216639.3
            RefSeq Select criteria :: based on conservation, expression
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..396
                     /organism="Homo sapiens"
                     /db_xref="taxon:9606"
                     /chromosome="14"
                     /map="14q32.2"
     Protein         1..396
                     /product="serine/threonine-protein kinase VRK1 isoform 1"
                     /EC_number="2.7.11.1"
                     /note="vaccinia virus B1R-related kinase 1;
                     serine/threonine-protein kinase VRK1; vaccinia related
                     kinase 1"
                     /calculated_mol_wt=45345
     Region          26..326
                     /region_name="STKc_VRK1"
                     /note="Catalytic domain of the Serine/Threonine protein
                     kinase, Vaccinia Related Kinase 1; cd14122"
                     /db_xref="CDD:271024"
     Site            order(43..47,51,69,71,111,131..134,137,139,177,179,
                     181..182,184,197,200,223..226)
                     /site_type="active"
                     /db_xref="CDD:271024"
     Site            order(43..47,51,69,71,111,131..134,137,177,179,181..182,
                     184,197)
                     /site_type="other"
                     /note="ATP binding site [chemical binding]"
                     /db_xref="CDD:271024"
     Site            order(47,137,139,177,179,181,200,223..226)
                     /site_type="other"
                     /note="polypeptide substrate binding site [polypeptide
                     binding]"
                     /db_xref="CDD:271024"
     Site            196..226
                     /site_type="other"
                     /note="activation loop (A-loop)"
                     /db_xref="CDD:271024"
     Site            342
                     /site_type="phosphorylation"
                     /note="Phosphoserine, by PLK3.
                     /evidence=ECO:0000269|PubMed:19103756,
                     ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163;
                     propagated from UniProtKB/Swiss-Prot (Q99986.1)"
     Region          354..396
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q99986.1)"
     Site            355
                     /site_type="phosphorylation"
                     /note="Phosphothreonine, by autocatalysis.
                     /evidence=ECO:0000269|PubMed:11883897; propagated from
                     UniProtKB/Swiss-Prot (Q99986.1)"
     Site            376
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (Q99986.1)"
     Site            378
                     /site_type="phosphorylation"
                     /note="Phosphothreonine.
                     /evidence=ECO:0007744|PubMed:23186163; propagated from
                     UniProtKB/Swiss-Prot (Q99986.1)"
     Region          387..393
                     /region_name="Required for interaction with the
                     nucleosome. /evidence=ECO:0000269|PubMed:35390161"
                     /note="propagated from UniProtKB/Swiss-Prot (Q99986.1)"
     CDS             1..396
                     /gene="VRK1"
                     /gene_synonym="HMNR10; PCH1; PCH1A"
                     /coded_by="NM_003384.3:72..1262"
                     /note="isoform 1 is encoded by transcript variant 1"
                     /db_xref="CCDS:CCDS9947.1"
                     /db_xref="GeneID:7443"
                     /db_xref="HGNC:HGNC:12718"
                     /db_xref="MIM:602168"
ORIGIN      
        1 mprvkaaqag rqssakrhla eqfavgeiit dmakkewkvg lpigqggfgc iyladmnsse
       61 svgsdapcvv kvepsdngpl ftelkfyqra akpeqiqkwi rtrklkylgv pkywgsglhd
      121 kngksyrfmi mdrfgsdlqk iyeanakrfs rktvlqlslr ildileyihe heyvhgdika
      181 snlllnyknp dqvylvdygl ayrycpegvh keykedpkrc hdgtieftsi dahngvapsr
      241 rgdleilgyc miqwltghlp wednlkdpky vrdskiryre niaslmdkcf peknkpgeia
      301 kymetvklld ytekplyenl rdillqglka igskddgkld lsvvengglk aktitkkrkk
      361 eieeskepgv edtewsntqt eeaiqtrsrt rkrvqk
//
