Recombinant Mouse AT-rich interactive domain-containing protein 5A (Arid5a)

Function

DNA-binding protein that may regulate transcription and act as a repressor by binding to AT-rich stretches in the promoter region of target genes (By similarity). May positively regulate chondrocyte-specific transcription such as of COL2A1 in collaboration with SOX9 and positively regulate histone H3 acetylation at chondrocyte-specific genes. May stimulate early-stage chondrocyte differentiation and inhibit later stage differention (PubMed:21346191). Can repress ESR1-mediated transcriptional activation; proposed to act as corepressor for selective nuclear hormone receptors (By similarity). As an RNA-binding protein, involved in the regulation of inflammatory response by stabilizing selective inflammation-related mRNAs, such as STAT3 and TBX21. Also stabilizes IL6 mRNA. Binds to stem loop structures located in the 3'UTRs of IL6, STAT3 and TBX21 mRNAs; at least for STAT3 prevents binding of ZC3H12A to the mRNA stem loop structure thus inhibiting its degradation activity. Contributes to elevated IL6 levels possibly implicated in autoimmunity processes. IL6-dependent stabilization of STAT3 mRNA may promote differentiation of naive CD4+ T-cells into T-helper Th17 cells (PubMed:23676272, PubMed:27022145). In CD4+ T-cells may also inhibit RORC-induced Th17 cell differentiation independently of IL6 signaling (PubMed:24782182). Stabilization of TBX21 mRNA contributes to elevated interferon-gamma secretion in Th1 cells possibly implicated in the establishment of septic shock (PubMed:27671645). Stabilizes TNFRSF4/OX40 mRNA by binding to the conserved stem loop structure in its 3'UTR; thereby competing with the mRNA-destabilizing functions of RC3H1 and endoribonuclease ZC3H12A (PubMed:29244194)

Subcellular Location

Nucleus

Tissue Specificity

Expressed in T cells (at protein level) (PubMed:29244194). Expressed at high levels in cartilage, heart, testis and bone (PubMed:21346191)

Subunit

Interacts with SOX9 (PubMed:21346191). Interacts with ESR1 (By similarity). Interacts with RORC (PubMed:24782182)

• Carninci P. et al. The transcriptional landscape of the mammalian genome. — Science (2005)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Huttlin E.L. et al. A tissue-specific atlas of mouse protein phosphorylation and expression. — Cell (2010)
• Amano K. et al. Arid5a cooperates with Sox9 to stimulate chondrocyte-specific transcription. — Mol. Biol. Cell (2011)
• Masuda K. et al. Arid5a controls IL-6 mRNA stability, which contributes to elevation of IL-6 level in vivo. — Proc. Natl. Acad. Sci. U.S.A. (2013)
• Saito Y. et al. AT-rich-interactive domain-containing protein 5A functions as a negative regulator of retinoic acid receptor-related orphan nuclear receptor gammat-induced Th17 cell differentiation. — Arthritis Rheum. (2014)
• Masuda K. et al. Arid5a regulates naive CD4+ T cell fate through selective stabilization of Stat3 mRNA. — J. Exp. Med. (2016)
• Zaman M.M. et al. Arid5a exacerbates IFN-gamma-mediated septic shock by stabilizing T-bet mRNA. — Proc. Natl. Acad. Sci. U.S.A. (2016)