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Overview

Uniprot ID	Q03989
Protein Name	AT-rich interactive domain-containing protein 5A
Gene Name	ARID5A
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
457	EGAAHSGKRLRAVSP

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 (PubMed:8649988). 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 (By similarity). Can repress ESR1-mediated transcriptional activation; proposed to act as corepressor for selective nuclear hormone receptors (PubMed:15941852). As an RNA-binding protein, involved in the regulation of inflammatory response by stabilizing selective inflammation-related mRNAs, such as STAT3 and TBX21 (By similarity). Also stabilizes IL6 mRNA (PubMed:32209697). 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. In CD4+ T-cells may also inhibit RORC-induced Th17 cell differentiation independently of IL6 signaling. Stabilization of TBX21 mRNA contributes to elevated interferon-gamma secretion in Th1 cells possibly implicated in the establishment of septic shock (By similarity). 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 (By similarity)

Protein Sequence

10 MAAPVKGNRK 20 QSTEGDALDP 30 PASPKPAGKQ 40 NGIQNPISLE 50 DSPEAGGERE 60 EEQEREEEQA 70 FLVSLYKFMK 80 ERHTPIERVP 90 HLGFKQINLW 100 KIYKAVEKLG 110 AYELVTGRRL 120 WKNVYDELGG 130 SPGSTSAATC 140 TRRHYERLVL 150 PYVRHLKGED 160 DKPLPTSKPR 170 KQYKMAKENR 180 GDDGATERPK 190 KAKEERRMDQ 200 MMPGKTKADA 210 ADPAPLPSQE 220 PPRNSTEQQG 230 LASGSSVSFV 240 GASGCPEAYK 250 RLLSSFYCKG 260 THGIMSPLAK 270 KKLLAQVSKV 280 EALQCQEEGC 290 RHGAEPQASP 300 AVHLPESPQS 310 PKGLTENSRH 320 RLTPQEGLQA 330 PGGSLREEAQ 340 AGPCPAAPIF 350 KGCFYTHPTE 360 VLKPVSQHPR 370 DFFSRLKDGV 380 LLGPPGKEGL 390 SVKEPQLVWG 400 GDANRPSAFH 410 KGGSRKGILY 420 PKPKACWVSP 430 MAKVPAESPT 440 LPPTFPSSPG 450 LGSKRSLEEE 460 GAAHSGKRLR 470 AVSPFLKEAD 480 AKKCGAKPAG 490 SGLVSCLLGP 500 ALGPVPPEAY 510 RGTMLHCPLN 520 FTGTPGPLKG 530 QAALPFSPLV 540 IPAFPAHFLA 550 TAGPSPMAAG 560 LMHFPPTSFD 570 SALRHRLCPA 580 SSAWHAPPVT 590 TYAAPHFFHL NTKL

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0005730	nucleolus
Cellular Component	GO:0005654	nucleoplasm
Cellular Component	GO:0005634	nucleus
Cellular Component	GO:0005667	transcription regulator complex
Molecular Function	GO:0003682	chromatin binding
Molecular Function	GO:0003677	DNA binding
Molecular Function	GO:0042802	identical protein binding
Molecular Function	GO:0035925	mRNA 3'-UTR AU-rich region binding
Molecular Function	GO:0050681	nuclear androgen receptor binding
Molecular Function	GO:0030331	nuclear estrogen receptor binding
Molecular Function	GO:0046965	nuclear retinoid X receptor binding
Molecular Function	GO:0046966	nuclear thyroid hormone receptor binding
Molecular Function	GO:0035613	RNA stem-loop binding
Molecular Function	GO:0043565	sequence-specific DNA binding
Molecular Function	GO:0000976	transcription cis-regulatory region binding
Molecular Function	GO:0003714	transcription corepressor activity
Molecular Function	GO:0008134	transcription factor binding
Biological Process	GO:0071391	cellular response to estrogen stimulus
Biological Process	GO:0071222	cellular response to lipopolysaccharide
Biological Process	GO:0006351	DNA-templated transcription
Biological Process	GO:0045087	innate immune response
Biological Process	GO:0045892	negative regulation of DNA-templated transcription
Biological Process	GO:0000122	negative regulation of transcription by RNA polymerase II
Biological Process	GO:1905870	positive regulation of 3'-UTR-mediated mRNA stabilization
Biological Process	GO:0032740	positive regulation of interleukin-17 production
Biological Process	GO:0032755	positive regulation of interleukin-6 production
Biological Process	GO:2000556	positive regulation of T-helper 1 cell cytokine production
Biological Process	GO:2000318	positive regulation of T-helper 17 type immune response
Biological Process	GO:0032760	positive regulation of tumor necrosis factor production
Biological Process	GO:0032729	positive regulation of type II interferon production
Biological Process	GO:0006357	regulation of transcription by RNA polymerase II

Reference

[1] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.