VRK2_HUMAN » Serine/threonine-protein kinase VRK2

VRK2_HUMAN » Serine/threonine-protein kinase VRK2
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Topology in Endoplasmic reticulum membrane
Topologylumenal side
cytoplasmic side
VRK2_HUMAN » Serine/threonine-protein kinase VRK2 » Vaccinia-related kinase 2;
Hydrophobic Thickness 29.8 ± 2.1 Å
Tilt Angle 2 ± 1°
ΔGtransfer -22.7 kcal/mol
ΔGfold -17.5 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, Reactome, HMDB
Topology In
TM Segments 489-508 (485-508)
Pathways

Cell Cycle (Reactome)

Mitotic M-M/G1 phases (Reactome)

PDB 2v62 (14-335)
OPM none
Complexes none
Interactions

B2CL1, Complex: B2CL1:VRK2, PubMed

BAX, Complex: BAX:VRK2, PubMed

BCL2, Complex: BCL2:VRK2, PubMed

Domains

AA: 29-311, PDBID: 2V62, Subunit A, Seq Identity:100%, Protein kinase domain

UniProt annotation for VRK2_HUMAN » Serine/threonine-protein kinase VRK2
FUNCTION: 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 "Thr-18" of p53/TP53, histone H3, and may also phosphorylate MAPK8IP1. 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. 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.

FUNCTION: Isoform 2 phosphorylates "Thr-18" of p53/TP53, as well as histone H3. Reduces p53/TP53 ubiquitination by MDM2, promotes p53/TP53 acetylation by EP300 and thereby increases p53/TP53 stability and activity.

CATALYTIC ACTIVITY: ATP + a protein = ADP + a phosphoprotein.

ENZYME REGULATION: RAN inhibits its autophosphorylation and its ability to phosphorylate histone H3.

SUBUNIT: Isoform 1 interacts with MAP3K7, MAP2K7, MAP2K1 and KSR1. Isoform 1 and isoform 2 interact with RAN and MAPK8IP1. Isoform 1 interacts with Epstein-Barr virus BHRF1; this interaction is involved in protecting cells from apoptosis.

TISSUE SPECIFICITY: Isoform 1 and isoform 2 are expressed in various tumor cell lines. Expression of isoform 1 inversely correlates with ERBB2 in breast carcinomas (at protein level). Widely expressed. Highly expressed in fetal liver, skeletal muscle, pancreas, heart, peripheral blood leukocytes and testis.

UniProt features for VRK2_HUMAN » Serine/threonine-protein kinase VRK2
CHAIN 1 508 Serine/threonine-protein kinase VRK2.
DOMAIN 29 319 Protein kinase.
REGION 397 508 Interaction with MAP3K7.
ACT_SITE 166 166 Proton acceptor (By similarity).
Amino Acid Sequence for VRK2_HUMAN » Serine/threonine-protein kinase VRK2
MPPKRNEKYK LPIPFPEGKV LDDMEGNQWV LGKKIGSGGF GLIYLAFPTN KPEKDARHVV KVEYQENGPL FSELKFYQRV AKKDCIKKWI ERKQLDYLGI PLFYGSGLTE FKGRSYRFMV MERLGIDLQK ISGQNGTFKK STVLQLGIRM LDVLEYIHEN EYVHGDIKAA NLLLGYKNPD QVYLADYGLS YRYCPNGNHK QYQENPRKGH NGTIEFTSLD AHKGVALSRR SDVEILGYCM LRWLCGKLPW EQNLKDPVAV QTAKTNLLDE LPQSVLKWAP SGSSCCEIAQ FLVCAHSLAY DEKPNYQALK KILNPHGIPL GPLDFSTKGQ SINVHTPNSQ KVDSQKAATK QVNKAHNRLI EKKVHSERSA ESCATWKVQK EEKLIGLMNN EAAQESTRRR QKYQESQEPL NEVNSFPQKI SYTQFPNSFY EPHQDFTSPD IFKKSRSPSW YKYTSTVSTG ITDLESSTGL WPTISQFTLS EETNADVYYY RIIIPVLLML VFLALFFL