Protein:VRK2 |
Protein Summary |
 Gene summary |
| Gene name: VRK2 | ASpdb.0 ID: 7444 | Gene | Gene symbol | VRK2 | Gene ID | 7444 |
| Gene name | VRK serine/threonine kinase 2 |
| Synonyms | - |
| Cytomap | 2p16.1 |
| Type of gene | protein-coding |
| Description | serine/threonine-protein kinase VRK2vaccinia related kinase 2vaccinia virus B1R-related kinase 2 |
| Modification date | 20240403 |
| UniProtAcc | Q86Y07 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | VRK2 | GO:0004674 | protein serine/threonine kinase activity | 14645249|16495336|16704422 |
| Gene | VRK2 | GO:0005634 | nucleus | 16704422 |
| Gene | VRK2 | GO:0005737 | cytoplasm | 16704422 |
| Gene | VRK2 | GO:0005783 | endoplasmic reticulum | 22572157 |
| Gene | VRK2 | GO:0005789 | endoplasmic reticulum membrane | 18286207 |
| Gene | VRK2 | GO:0019901 | protein kinase binding | 22572157 |
| Gene | VRK2 | GO:0019904 | protein domain specific binding | 22572157 |
| Gene | VRK2 | GO:0031966 | mitochondrial membrane | 18286207 |
| Gene | VRK2 | GO:0032991 | protein-containing complex | 22572157 |
| Gene | VRK2 | GO:0046777 | protein autophosphorylation | 14645249|16704422 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| Q86Y07-1 | Q86Y07-1_2v62_A.pdb | 2V62 | X-ray | 1.7 | A | 15 | 330 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| Q86Y07 | VRK2 | Q86Y07-1 | Q86Y07-2 | 508 | 397 | 395 | 397 | Substitution | EST | VEA | 395 | 397 |
| Q86Y07 | VRK2 | Q86Y07-1 | Q86Y07-2 | 508 | 397 | 398 | 508 | Deletion | none | none | 397 | 397 |
| Q86Y07 | VRK2 | Q86Y07-1 | Q86Y07-3 | 508 | 485 | 1 | 23 | Deletion | none | none | 0 | 0 |
| Q86Y07 | VRK2 | Q86Y07-1 | Q86Y07-4 | 508 | 390 | 1 | 118 | Deletion | none | none | 0 | 0 |
| Q86Y07 | VRK2 | Q86Y07-1 | Q86Y07-5 | 508 | 396 | 395 | 396 | Substitution | ES | FR | 395 | 396 |
| Q86Y07 | VRK2 | Q86Y07-1 | Q86Y07-5 | 508 | 396 | 397 | 508 | Deletion | none | none | 396 | 396 |
| Multiple sequence alignment of our canonical and alternatively spliced VRK2 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of VRK2 |
| UniProt-id | ENSG | ENST | ENSP |
| Q86Y07-1 | ENSG00000028116.18 | ENST00000340157.9 | ENSP00000342381.4 |
| Q86Y07-1 | ENSG00000028116.18 | ENST00000435505.6 | ENSP00000408002.2 |
| Q86Y07-2 | ENSG00000028116.18 | ENST00000648897.1 | ENSP00000497378.1 |
| Q86Y07-3 | ENSG00000028116.18 | ENST00000440705.6 | ENSP00000398323.2 |
| Q86Y07-4 | ENSG00000028116.18 | ENST00000412104.6 | ENSP00000404156.3 |
| Q86Y07-5 | ENSG00000028116.18 | ENST00000417641.6 | ENSP00000402375.2 |
| UniProt-id | NM ID | NP ID |
| Q86Y07-1 | NM_001130480.2 | NP_001123952.1 |
| Q86Y07-1 | NM_001130481.2 | NP_001123953.1 |
| Q86Y07-1 | NM_001288837.1 | NP_001275766.1 |
| Q86Y07-1 | NM_006296.6 | NP_006287.2 |
| Q86Y07-1 | XM_005264540.4 | XP_005264597.1 |
| Q86Y07-1 | XM_011533092.2 | XP_011531394.1 |
| Q86Y07-2 | XM_006712090.3 | XP_006712153.1 |
| Q86Y07-3 | NM_001130482.2 | NP_001123954.1 |
| Q86Y07-4 | NM_001288836.1 | NP_001275765.1 |
| Q86Y07-4 | NM_001288839.1 | NP_001275768.1 |
| Q86Y07-5 | NM_001130483.2 | NP_001123955.1 |
| Q86Y07-5 | NM_001288838.1 | NP_001275767.1 |
| Q86Y07-5 | XM_006712091.3 | XP_006712154.1 |
| Amino acid sequences of our canonical and alternatively spliced VRK2 |
| accession_id | Protein sequence |
| Q86Y07-1 | MPPKRNEKYKLPIPFPEGKVLDDMEGNQWVLGKKIGSGGFGLIYLAFPTNKPEKDARHVVKVEYQENGPLFSELKFYQRVAKKDCIKKWI ERKQLDYLGIPLFYGSGLTEFKGRSYRFMVMERLGIDLQKISGQNGTFKKSTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLLGYKNPD QVYLADYGLSYRYCPNGNHKQYQENPRKGHNGTIEFTSLDAHKGVALSRRSDVEILGYCMLRWLCGKLPWEQNLKDPVAVQTAKTNLLDE LPQSVLKWAPSGSSCCEIAQFLVCAHSLAYDEKPNYQALKKILNPHGIPLGPLDFSTKGQSINVHTPNSQKVDSQKAATKQVNKAHNRLI EKKVHSERSAESCATWKVQKEEKLIGLMNNEAAQESTRRRQKYQESQEPLNEVNSFPQKISYTQFPNSFYEPHQDFTSPDIFKKSRSPSW |
| Q86Y07-2 | MPPKRNEKYKLPIPFPEGKVLDDMEGNQWVLGKKIGSGGFGLIYLAFPTNKPEKDARHVVKVEYQENGPLFSELKFYQRVAKKDCIKKWI ERKQLDYLGIPLFYGSGLTEFKGRSYRFMVMERLGIDLQKISGQNGTFKKSTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLLGYKNPD QVYLADYGLSYRYCPNGNHKQYQENPRKGHNGTIEFTSLDAHKGVALSRRSDVEILGYCMLRWLCGKLPWEQNLKDPVAVQTAKTNLLDE LPQSVLKWAPSGSSCCEIAQFLVCAHSLAYDEKPNYQALKKILNPHGIPLGPLDFSTKGQSINVHTPNSQKVDSQKAATKQVNKAHNRLI |
| Q86Y07-3 | MEGNQWVLGKKIGSGGFGLIYLAFPTNKPEKDARHVVKVEYQENGPLFSELKFYQRVAKKDCIKKWIERKQLDYLGIPLFYGSGLTEFKG RSYRFMVMERLGIDLQKISGQNGTFKKSTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLLGYKNPDQVYLADYGLSYRYCPNGNHKQYQ ENPRKGHNGTIEFTSLDAHKGVALSRRSDVEILGYCMLRWLCGKLPWEQNLKDPVAVQTAKTNLLDELPQSVLKWAPSGSSCCEIAQFLV CAHSLAYDEKPNYQALKKILNPHGIPLGPLDFSTKGQSINVHTPNSQKVDSQKAATKQVNKAHNRLIEKKVHSERSAESCATWKVQKEEK LIGLMNNEAAQESTRRRQKYQESQEPLNEVNSFPQKISYTQFPNSFYEPHQDFTSPDIFKKSRSPSWYKYTSTVSTGITDLESSTGLWPT |
| Q86Y07-4 | MVMERLGIDLQKISGQNGTFKKSTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLLGYKNPDQVYLADYGLSYRYCPNGNHKQYQENPRK GHNGTIEFTSLDAHKGVALSRRSDVEILGYCMLRWLCGKLPWEQNLKDPVAVQTAKTNLLDELPQSVLKWAPSGSSCCEIAQFLVCAHSL AYDEKPNYQALKKILNPHGIPLGPLDFSTKGQSINVHTPNSQKVDSQKAATKQVNKAHNRLIEKKVHSERSAESCATWKVQKEEKLIGLM NNEAAQESTRRRQKYQESQEPLNEVNSFPQKISYTQFPNSFYEPHQDFTSPDIFKKSRSPSWYKYTSTVSTGITDLESSTGLWPTISQFT |
| Q86Y07-5 | MPPKRNEKYKLPIPFPEGKVLDDMEGNQWVLGKKIGSGGFGLIYLAFPTNKPEKDARHVVKVEYQENGPLFSELKFYQRVAKKDCIKKWI ERKQLDYLGIPLFYGSGLTEFKGRSYRFMVMERLGIDLQKISGQNGTFKKSTVLQLGIRMLDVLEYIHENEYVHGDIKAANLLLGYKNPD QVYLADYGLSYRYCPNGNHKQYQENPRKGHNGTIEFTSLDAHKGVALSRRSDVEILGYCMLRWLCGKLPWEQNLKDPVAVQTAKTNLLDE LPQSVLKWAPSGSSCCEIAQFLVCAHSLAYDEKPNYQALKKILNPHGIPLGPLDFSTKGQSINVHTPNSQKVDSQKAATKQVNKAHNRLI |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| VRK2 (go to UniProt):Q86Y07 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Q86Y07 | Transmembrane | 487 | 507 | Note=Helical%3B Anchor for type IV membrane protein;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=398;End=508 |
| Q86Y07 | Transmembrane | 487 | 507 | Note=Helical%3B Anchor for type IV membrane protein;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=397;End=508 |
| Q86Y07 | Domain | 29 | 319 | Note=Protein kinase;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00159 | Type=Deletion;Start=1;End=118 |
| Q86Y07 | Region | 397 | 508 | Note=Interaction with MAP3K7;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17709393;Dbxref=PMID:17709393 | Type=Substitution;Start=395;End=397 |
| Q86Y07 | Region | 397 | 508 | Note=Interaction with MAP3K7;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17709393;Dbxref=PMID:17709393 | Type=Deletion;Start=398;End=508 |
| Q86Y07 | Region | 397 | 508 | Note=Interaction with MAP3K7;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17709393;Dbxref=PMID:17709393 | Type=Deletion;Start=397;End=508 |
Gene Isoform Structures and Expression Levels for VRK2 |
| Gene structures of our canonical and alternative spliced genes of VRK2 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of Q86Y07-1 |
| 3D view using mol* of Q86Y07-2 |
| 3D view using mol* of Q86Y07-3 |
| 3D view using mol* of Q86Y07-4 |
| 3D view using mol* of Q86Y07-5 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of Q86Y07-1 |
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| pLDDT distribution across the protein length of Q86Y07-2 |
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| pLDDT distribution across the protein length of Q86Y07-3 |
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| pLDDT distribution across the protein length of Q86Y07-4 |
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| pLDDT distribution across the protein length of Q86Y07-5 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of Q86Y07-1 |
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| Ramachandran plot of Q86Y07-3 |
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| Ramachandran plot of Q86Y07-4 |
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| Ramachandran plot of Q86Y07-5 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| Q86Y07-1 | 1.006 | 485 | 1.022 | 1866.606 | 0.553 | 0.707 | 0.922 | 0.595 | 1.05 | 0.566 | 0.878 | 5,6,9,10,11,35,36,38,39,40,41,43,59,61,63,69,73,77 ,121,122,123,124,125,127,129,132,136,165,166,168,1 69,170,171,173,185,186,188,189,191,201,203,204,205 ,207,208,209,210,211,212,213,214,215,216,221,224,2 25,226,227,242,243,254,255,257,300,349,351,352,353 ,355,356,357,358,359,360,361,362,363,364,366,367,3 69,370,373,374,377,378,381 |
| Q86Y07-2 | 1.02 | 491 | 1.004 | 1860.089 | 0.55 | 0.727 | 0.962 | 0.599 | 1.142 | 0.525 | 0.807 | 8,9,10,11,33,35,36,37,38,39,40,41,43,59,61,63,66,6 7,68,69,72,73,75,77,79,121,122,123,124,125,126,127 ,129,130,131,132,136,162,165,166,168,169,170,171,1 73,174,175,176,179,185,186,188,189,190,191,192,200 ,201,202,203,205,208,210,211,212,213,214,215,216,2 17,221,224,225,226,227,239,242,243,254,300,325,326 ,327,330,332,334,335,336,337,338,339,340,341,342,3 43,344,345,346,347,348,349,351,352,355,356,359 |
| Q86Y07-3 | 1.037 | 96 | 1.11 | 267.883 | 0.635 | 0.657 | 0.91 | 1.443 | 0.629 | 2.294 | 0.589 | 1,2,3,4,5,6,8,14,15,17,18,19,21,37,39,40,41,44,55, 80,82,83,84,86,88,93,95,97 |
| Q86Y07-4 | 0.836 | 53 | 0.839 | 112.504 | 0.547 | 0.67 | 0.942 | 1.582 | 0.757 | 2.089 | 0.552 | 22,23,24,26,27,30,169,195,196,197,198,200,202,203, 204,205,206 |
| Q86Y07-5 | 1.02 | 555 | 1.046 | 2038.792 | 0.561 | 0.711 | 0.935 | 0.749 | 0.984 | 0.761 | 0.866 | 5,8,9,33,34,35,36,37,38,39,40,41,43,59,61,63,66,67 ,68,69,72,73,75,77,79,121,123,124,125,126,127,129, 130,131,162,166,168,170,171,173,174,175,176,179,18 5,186,187,188,189,190,191,192,200,201,203,205,206, 207,208,209,210,211,212,213,214,221,224,225,226,22 7,254,255,256,257,323,324,325,326,327,330,331,332, 334,335,336,337,338,339,340,341,342,345,348,349,35 0,351,352,353,354,355,356,358,359,360,362,363,366 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of Q86Y07-1_Q86Y07-1_2v62_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q86Y07-1_2v62_A_Q86Y07-2.pdb |
| 3D view using mol* of Q86Y07-1_2v62_A_Q86Y07-3.pdb |
| 3D view using mol* of Q86Y07-1_2v62_A_Q86Y07-4.pdb |
| 3D view using mol* of Q86Y07-1_2v62_A_Q86Y07-5.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of Q86Y07-1_Q86Y07-2.pdb |
| 3D view using mol* of Q86Y07-1_Q86Y07-3.pdb |
| 3D view using mol* of Q86Y07-1_Q86Y07-4.pdb |
| 3D view using mol* of Q86Y07-1_Q86Y07-5.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/Q86Y07-1_vs_Q86Y07-2.png |
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| ./stats/secondary_structure/figure/Q86Y07-1_vs_Q86Y07-3.png |
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| ./stats/secondary_structure/figure/Q86Y07-1_vs_Q86Y07-4.png |
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| ./stats/secondary_structure/figure/Q86Y07-1_vs_Q86Y07-5.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/Q86Y07-1_vs_Q86Y07-2.png |
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| ./stats/relative_asa/Q86Y07-1_vs_Q86Y07-3.png |
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| ./stats/relative_asa/Q86Y07-1_vs_Q86Y07-4.png |
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| ./stats/relative_asa/Q86Y07-1_vs_Q86Y07-5.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Q86Y07 | Region | 397 | 508 | Note=Interaction with MAP3K7;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17709393;Dbxref=PMID:17709393 | Type=Substitution;Start=395;End=397 |
| Q86Y07 | Region | 397 | 508 | Note=Interaction with MAP3K7;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17709393;Dbxref=PMID:17709393 | Type=Deletion;Start=398;End=508 |
| Q86Y07 | Region | 397 | 508 | Note=Interaction with MAP3K7;Ontology_term=ECO:0000269;evidence=ECO:0000269|PubMed:17709393;Dbxref=PMID:17709393 | Type=Deletion;Start=397;End=508 |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to VRK2 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
Related Diseases to VRK2 |
| Previous studies relating to the alternative splicing of VRK2 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| VRK2 | 16704422 | The subcellular localization of vaccinia-related kinase-2 (VRK2) isoforms determines their different effect on p53 stability in tumour cell lines. | VRK is a new kinase family of unknown function. Endogenous human vacinia-related kinase 2 (VRK2) protein is present in both the nucleus and the cytosol, which is a consequence of alternative splicing of two VRK2 messages coding for proteins of 508 and 397 amino acids, respectively. VRK2A has a C-terminal hydrophobic region that anchors the protein to membranes in the endoplasmic reticulum (ER) and mitochondria, and it colocalizes with calreticulin, calnexin and mitotracker; whereas VRK2B is detected in both the cytoplasm and the nucleus. VRK2A is expressed in all cell types, whereas VRK2B is expressed in cell lines in which VRK1 is cytoplasmic. Both VRK2 isoforms have an identical catalytic N-terminal domain and phosphorylate p53 in vitro uniquely in Thr18. Phosphorylation of the p53 protein in response to cellular stresses results in its stabilization by modulating its binding to other proteins. However, p53 phosphorylation also occurs in the absence of stress. Only overexpression of the nuclear VRK2B isoform induces p53 stabilization by post-translational modification, largely due to Thr18 phosphorylation. VRK2B may play a role in controlling the binding specificity of the N-terminal transactivation domain of p53. Indeed, the p53 phosphorylated by VRK2B shows a reduction in ubiquitination by Mdm2 and an increase in acetylation by p300. Endogenous p53 is also phosphorylated in Thr18 by VRK2B, promoting its stabilization and transcriptional activation in A549 cells. The relative phosphorylation of Thr18 by VRK2B is similar in magnitude to that induced by taxol, which might use a different signalling pathway. In this context, VRK2B kinase might functionally replace nuclear VRK1. Therefore, these kinases might be components of a new signalling pathway that is likely to play a role in normal cell proliferation. | D001943 | Breast Neoplasms |
| VRK2 | 16704422 | The subcellular localization of vaccinia-related kinase-2 (VRK2) isoforms determines their different effect on p53 stability in tumour cell lines. | VRK is a new kinase family of unknown function. Endogenous human vacinia-related kinase 2 (VRK2) protein is present in both the nucleus and the cytosol, which is a consequence of alternative splicing of two VRK2 messages coding for proteins of 508 and 397 amino acids, respectively. VRK2A has a C-terminal hydrophobic region that anchors the protein to membranes in the endoplasmic reticulum (ER) and mitochondria, and it colocalizes with calreticulin, calnexin and mitotracker; whereas VRK2B is detected in both the cytoplasm and the nucleus. VRK2A is expressed in all cell types, whereas VRK2B is expressed in cell lines in which VRK1 is cytoplasmic. Both VRK2 isoforms have an identical catalytic N-terminal domain and phosphorylate p53 in vitro uniquely in Thr18. Phosphorylation of the p53 protein in response to cellular stresses results in its stabilization by modulating its binding to other proteins. However, p53 phosphorylation also occurs in the absence of stress. Only overexpression of the nuclear VRK2B isoform induces p53 stabilization by post-translational modification, largely due to Thr18 phosphorylation. VRK2B may play a role in controlling the binding specificity of the N-terminal transactivation domain of p53. Indeed, the p53 phosphorylated by VRK2B shows a reduction in ubiquitination by Mdm2 and an increase in acetylation by p300. Endogenous p53 is also phosphorylated in Thr18 by VRK2B, promoting its stabilization and transcriptional activation in A549 cells. The relative phosphorylation of Thr18 by VRK2B is similar in magnitude to that induced by taxol, which might use a different signalling pathway. In this context, VRK2B kinase might functionally replace nuclear VRK1. Therefore, these kinases might be components of a new signalling pathway that is likely to play a role in normal cell proliferation. | D003110 | Colonic Neoplasms |
| VRK2 | 16704422 | The subcellular localization of vaccinia-related kinase-2 (VRK2) isoforms determines their different effect on p53 stability in tumour cell lines. | VRK is a new kinase family of unknown function. Endogenous human vacinia-related kinase 2 (VRK2) protein is present in both the nucleus and the cytosol, which is a consequence of alternative splicing of two VRK2 messages coding for proteins of 508 and 397 amino acids, respectively. VRK2A has a C-terminal hydrophobic region that anchors the protein to membranes in the endoplasmic reticulum (ER) and mitochondria, and it colocalizes with calreticulin, calnexin and mitotracker; whereas VRK2B is detected in both the cytoplasm and the nucleus. VRK2A is expressed in all cell types, whereas VRK2B is expressed in cell lines in which VRK1 is cytoplasmic. Both VRK2 isoforms have an identical catalytic N-terminal domain and phosphorylate p53 in vitro uniquely in Thr18. Phosphorylation of the p53 protein in response to cellular stresses results in its stabilization by modulating its binding to other proteins. However, p53 phosphorylation also occurs in the absence of stress. Only overexpression of the nuclear VRK2B isoform induces p53 stabilization by post-translational modification, largely due to Thr18 phosphorylation. VRK2B may play a role in controlling the binding specificity of the N-terminal transactivation domain of p53. Indeed, the p53 phosphorylated by VRK2B shows a reduction in ubiquitination by Mdm2 and an increase in acetylation by p300. Endogenous p53 is also phosphorylated in Thr18 by VRK2B, promoting its stabilization and transcriptional activation in A549 cells. The relative phosphorylation of Thr18 by VRK2B is similar in magnitude to that induced by taxol, which might use a different signalling pathway. In this context, VRK2B kinase might functionally replace nuclear VRK1. Therefore, these kinases might be components of a new signalling pathway that is likely to play a role in normal cell proliferation. | D008113 | Liver Neoplasms |
| VRK2 | 16704422 | The subcellular localization of vaccinia-related kinase-2 (VRK2) isoforms determines their different effect on p53 stability in tumour cell lines. | VRK is a new kinase family of unknown function. Endogenous human vacinia-related kinase 2 (VRK2) protein is present in both the nucleus and the cytosol, which is a consequence of alternative splicing of two VRK2 messages coding for proteins of 508 and 397 amino acids, respectively. VRK2A has a C-terminal hydrophobic region that anchors the protein to membranes in the endoplasmic reticulum (ER) and mitochondria, and it colocalizes with calreticulin, calnexin and mitotracker; whereas VRK2B is detected in both the cytoplasm and the nucleus. VRK2A is expressed in all cell types, whereas VRK2B is expressed in cell lines in which VRK1 is cytoplasmic. Both VRK2 isoforms have an identical catalytic N-terminal domain and phosphorylate p53 in vitro uniquely in Thr18. Phosphorylation of the p53 protein in response to cellular stresses results in its stabilization by modulating its binding to other proteins. However, p53 phosphorylation also occurs in the absence of stress. Only overexpression of the nuclear VRK2B isoform induces p53 stabilization by post-translational modification, largely due to Thr18 phosphorylation. VRK2B may play a role in controlling the binding specificity of the N-terminal transactivation domain of p53. Indeed, the p53 phosphorylated by VRK2B shows a reduction in ubiquitination by Mdm2 and an increase in acetylation by p300. Endogenous p53 is also phosphorylated in Thr18 by VRK2B, promoting its stabilization and transcriptional activation in A549 cells. The relative phosphorylation of Thr18 by VRK2B is similar in magnitude to that induced by taxol, which might use a different signalling pathway. In this context, VRK2B kinase might functionally replace nuclear VRK1. Therefore, these kinases might be components of a new signalling pathway that is likely to play a role in normal cell proliferation. | D008175 | Lung Neoplasms |
Clinically important variants in VRK2 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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