Mouse anti-Human sapiens (Human) VRK1 Monoclonal Antibody

Function

Serine/threonine kinase involved in the regulation of key cellular processes including the cell cycle, nuclear condensation, transcription regulation, and DNA damage response (PubMed:14645249, PubMed:18617507, PubMed:19103756, PubMed:33076429). Controls chromatin organization and remodeling by mediating phosphorylation of histone H3 on 'Thr-4' and histone H2AX (H2aXT4ph) (PubMed:31527692, PubMed:37179361). It also phosphorylates KAT5 in response to DNA damage, promoting KAT5 association with chromatin and histone acetyltransferase activity (PubMed:33076429). Is involved in the regulation of cell cycle progression of neural progenitors, and is required for proper cortical neuronal migration (By similarity). Is involved in neurite elongation and branching in motor neurons, and has an essential role in Cajal bodies assembly, acting through COIL phosphorylation and the control of coilin degradation (PubMed:21920476, PubMed:31090908, PubMed:31527692). Involved in Golgi disassembly during the cell cycle: following phosphorylation by PLK3 during mitosis, it is required to induce Golgi fragmentation (PubMed:19103756). Phosphorylates BANF1: disrupts its ability to bind DNA, reduces its binding to LEM domain-containing proteins and causes its relocalization from the nucleus to the cytoplasm (PubMed:16495336). Phosphorylates TP53BP1 and p53/TP53 on 'Thr-18', preventing the interaction between p53/TP53 and MDM2 (PubMed:10951572, PubMed:31527692). Phosphorylates ATF2 which activates its transcriptional activity (PubMed:15105425). Phosphorylates JUN (PubMed:31527692)

Subcellular Location

Nucleus; Cytoplasm; Nucleus, Cajal body

Disease Association

Pontocerebellar hypoplasia 1A (PCH1A) : A form of pontocerebellar hypoplasia, a disorder characterized by structural defects of the pons and cerebellum, evident upon brain imaging. PCH1A is an autosomal recessive form characterized by an abnormally small cerebellum and brainstem, central and peripheral motor dysfunction from birth, gliosis and spinal cord anterior horn cells degeneration resembling infantile spinal muscular atrophy. Additional features include muscle hypotonia, congenital contractures and respiratory insufficiency that is evident at birth. [The disease is caused by variants affecting the gene represented in this entry] | Neuronopathy, distal hereditary motor, autosomal recessive 10 (HMNR10) : A form of distal hereditary motor neuronopathy, a heterogeneous group of neuromuscular diseases caused by selective degeneration of motor neurons in the anterior horn of the spinal cord, without sensory deficit in the posterior horn. HMNR10 is a slowly progressive form characterized by distal muscle weakness and atrophy predominantly affecting the lower limbs, and resulting in gait abnormalities. Upper limb involvement is seen in some patients. HMNR10 has mostly juvenile or adult onset, although symptoms may manifest in infancy or childhood in some patients. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Widely expressed. Highly expressed in fetal liver, testis and thymus

Subunit

(Microbial infection) Interacts with vaccinia protein B12; this interaction inhibits the repressive activity of the vaccinia virus B12 pseudokinase on viral replication factory formation

• Nezu J. et al. Identification of two novel human putative serine/threonine kinases, VRK1 and VRK2, with structural similarity to Vaccinia virus B1R kinase. — Genomics (1997)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Lopez-Borges S. et al. The human vaccinia-related kinase 1 (VRK1) phosphorylates threonine-18 within the mdm-2 binding site of the p53 tumour suppressor protein. — Oncogene (2000)
• Barcia R. et al. Kinetic properties of p53 phosphorylation by the human vaccinia-related kinase 1. — Arch. Biochem. Biophys. (2002)
• Nichols R.J. et al. Characterization of three paralogous members of the Mammalian vaccinia related kinase family. — J. Biol. Chem. (2004)
• Sevilla A. et al. Human vaccinia-related kinase 1 (VRK1) activates the ATF2 transcriptional activity by novel phosphorylation on Thr-73 and Ser-62 and cooperates with JNK. — J. Biol. Chem. (2004)
• Blanco S. et al. The subcellular localization of vaccinia-related kinase-2 (VRK2) isoforms determines their different effect on p53 stability in tumour cell lines. — FEBS J. (2006)
• Nichols R.J. et al. The vaccinia-related kinases phosphorylate the N' terminus of BAF, regulating its interaction with DNA and its retention in the nucleus. — Mol. Biol. Cell (2006)