Dual specificity tyrosine-phosphorylation-regulated kinase 2

Dual specificity tyrosine-phosphorylation-regulated kinase 2

Serine/threonine-protein kinase involved in the regulation of the mitotic cell cycle, cell proliferation, apoptosis, organization of the cytoskeleton and neurite outgrowth11311121,12588975,16511445,16611631,17349958,18599021,22307329,9748265. Phosphorylates CRMP2/DPYSL2, CRMP4/DPYSL3, DCX, EIF2B5, EIF4EBP1, GLI2, GLI3, GYS1, JUN, MDM2, MYC, NFATC1, p53/TP53, TAU/MAPT and KATNA111311121,12588975,16511445,16611631,17349958,18599021,22307329,38968120. Can phosphorylate histone H1, histone H3 and histone H2B (in vitro)9748265. Can phosphorylate CARHSP1 (in vitro)15910284. Functions in part via its role in ubiquitin-dependent proteasomal protein degradation9748265. Functions downstream of ATM and phosphorylates p53/TP53 at 'Ser-46', and thereby contributes to the induction of apoptosis in response to DNA damage17349958,18599021. Phosphorylates NFATC1, and thereby inhibits its accumulation in the nucleus and its transcription factor activity16511445. May play a general role in the priming of GSK3 substrates11311121,16611631. Phosphorylates EIF2B5 at 'Ser-544', enabling its subsequent phosphorylation and inhibition by GSK3B11311121. Likewise, phosphorylation of NFATC1, CRMP2/DPYSL2 and CRMP4/DPYSL3 promotes their subsequent phosphorylation by GSK3B16611631. Inactivates GYS1 by phosphorylation at 'Ser-641', and potentially also a second phosphorylation site, thus regulating glycogen synthesis14593110. Mediates EDVP E3 ligase complex formation and is required for the phosphorylation and subsequent degradation of KATNA119287380. Phosphorylates TERT at 'Ser-457', promoting TERT ubiquitination by the EDVP complex23362280. Phosphorylates SIAH2, and thereby increases its ubiquitin ligase activity22878263. Promotes the proteasomal degradation of MYC and JUN, and thereby regulates progress through the mitotic cell cycle and cell proliferation22307329. Acts as a positive regulator of smoothened signaling by mediating phosphorylation of GLI2 and GLI3 in response to smoothened activation, promoting their dissociation from SUFU inhibitor and translocation to the nucleus38968120. Can also acts as a negative regulator of smoothened by catalyzing phosphorylation of GLI2 and GLI3 and promote their proteasomal degradation18455992. Plays a role in cytoskeleton organization and neurite outgrowth via its phosphorylation of DCX and DPYSL2 (By similarity)

Quoted from UniProt’s FUNCTION annotation for Q92630 (reviewed). The superscript numbers are UniProt’s own PubMed citations, kept in the sentence and in order, each linking to the paper it names.

What it acts with

STRING’s highest-confidence human functional partners. The combined score mixes several kinds of evidence, so each channel is shown separately — a partner supported by experiment is a different claim from one supported only by text mining, and for a receptor this is where its coupling appears as evidence rather than as assertion.

Where it sits in the cell

• Nucleoplasm
• Cytosoladditional

Human Protein Atlas, by antibody immunofluorescence in cell lines — a different assay from the expression figures below, which are RNA.

UniProt, curated Cytoplasm · Nucleus

Expression by cell type

Single cell type RNA, the 2 highest of those the Human Protein Atlas reports for this gene. Transcript, not protein, and a cell type rather than a tissue.

• Colonocytes86.8 nCPM
• Goblet cells81 nCPM