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Overview

Uniprot IDP31483
Protein NameCytotoxic granule associated RNA binding protein TIA1
Gene NameTIA1
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
190 TRKPPAPKSTYESNT
88 ATTPSSQKKDTSSST
89 TTPSSQKKDTSSSTV

Function

RNA-binding protein involved in the regulation of alternative pre-RNA splicing and mRNA translation by binding to uridine-rich (U-rich) RNA sequences (PubMed:11106748, PubMed:12486009, PubMed:17488725, PubMed:8576255). Binds to U-rich sequences immediately downstream from a 5' splice sites in a uridine-rich small nuclear ribonucleoprotein (U snRNP)-dependent fashion, thereby modulating alternative pre-RNA splicing (PubMed:11106748, PubMed:8576255). Preferably binds to the U-rich IAS1 sequence in a U1 snRNP-dependent manner; this binding is optimal if a 5' splice site is adjacent to IAS1 (By similarity). Activates the use of heterologous 5' splice sites; the activation depends on the intron sequence downstream from the 5' splice site, with a preference for a downstream U-rich sequence (PubMed:11106748). By interacting with SNRPC/U1-C, promotes recruitment and binding of spliceosomal U1 snRNP to 5' splice sites followed by U-rich sequences, thereby facilitating atypical 5' splice site recognition by U1 snRNP (PubMed:11106748, PubMed:12486009, PubMed:17488725). Activates splicing of alternative exons with weak 5' splice sites followed by a U-rich stretch on its own pre-mRNA and on TIAR mRNA (By similarity). Acts as a modulator of alternative splicing for the apoptotic FAS receptor, thereby promoting apoptosis (PubMed:11106748, PubMed:17488725, PubMed:1934064). Binds to the 5' splice site region of FAS intron 5 to promote accumulation of transcripts that include exon 6 at the expense of transcripts in which exon 6 is skipped, thereby leading to the transcription of a membrane-bound apoptotic FAS receptor, which promotes apoptosis (PubMed:11106748, PubMed:17488725, PubMed:1934064). Binds to a conserved AU-rich cis element in COL2A1 intron 2 and modulates alternative splicing of COL2A1 exon 2 (PubMed:17580305). Also binds to the equivalent AT-rich element in COL2A1 genomic DNA, and may thereby be involved in the regulation of transcription (PubMed:17580305). Binds specifically to a polypyrimidine-rich controlling element (PCE) located between the weak 5' splice site and the intronic splicing silencer of CFTR mRNA to promote exon 9 inclusion, thereby antagonizing PTB1 and its role in exon skipping of CFTR exon 9 (PubMed:14966131). Involved in the repression of mRNA translation by binding to AU-rich elements (AREs) located in mRNA 3' untranslated regions (3' UTRs), including target ARE-bearing mRNAs encoding TNF and PTGS2 (By similarity). Also participates in the cellular response to environmental stress, by acting downstream of the stress-induced phosphorylation of EIF2S1/EIF2A to promote the recruitment of untranslated mRNAs to cytoplasmic stress granules (SGs), leading to stress-induced translational arrest (PubMed:10613902). Formation and recruitment to SGs is regulated by Zn(2+) (By similarity). Possesses nucleolytic activity against cytotoxic lymphocyte target cells (PubMed:1934064)

Protein Sequence

10 MEDEMPKTLY 20 VGNLSRDVTE 30 ALILQLFSQI 40 GPCKNCKMIM 50 DTAGNDPYCF 60 VEFHEHRHAA 70 AALAAMNGRK 80 IMGKEVKVNW 90 ATTPSSQKKD 100 TSSSTVVSTQ 110 RSQDHFHVFV 120 GDLSPEITTE 130 DIKAAFAPFG 140 RISDARVVKD 150 MATGKSKGYG 160 FVSFFNKWDA 170 ENAIQQMGGQ 180 WLGGRQIRTN 190 WATRKPPAPK 200 STYESNTKQL 210 SYDEVVNQSS 220 PSNCTVYCGG 230 VTSGLTEQLM 240 RQTFSPFGQI 250 MEIRVFPDKG 260 YSFVRFNSHE 270 SAAHAIVSVN 280 GTTIEGHVVK 290 CYWGKETLDM 300 INPVQQQNQI 310 GYPQPYGQWG 320 QWYGNAQQIG 330 QYMPNGWQVP 340 AYGMYGQAWN 350 QQGFNQTQSS 360 APWMGPNYGV 370 QPPQGQNGSM 380 LPNQPSGYRV AGYETQ

Gene Ontology

Classification GO ID Description
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0010494 cytoplasmic stress granule
Cellular Component GO:0005829 cytosol
Cellular Component GO:0097165 nuclear stress granule
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Cellular Component GO:1990904 ribonucleoprotein complex
Molecular Function GO:0035925 mRNA 3'-UTR AU-rich region binding
Molecular Function GO:0003730 mRNA 3'-UTR binding
Molecular Function GO:0008143 poly(A) binding
Molecular Function GO:0140517 protein-RNA adaptor activity
Molecular Function GO:0003723 RNA binding
Biological Process GO:0006915 apoptotic process
Biological Process GO:0006397 mRNA processing
Biological Process GO:0017148 negative regulation of translation
Biological Process GO:1904037 positive regulation of epithelial cell apoptotic process
Biological Process GO:1903608 protein localization to cytoplasmic stress granule
Biological Process GO:0000381 regulation of alternative mRNA splicing, via spliceosome
Biological Process GO:0048024 regulation of mRNA splicing, via spliceosome
Biological Process GO:0008380 RNA splicing
Biological Process GO:0034063 stress granule assembly

Reference

[1] Guo X, Ren X, Yan C, Huang H. Quantitative Proteomics Reveals the Role of Lysine Lactylation in Lenalidomide-Resistance in Multiple Myeloma Cells.. ACS Chem Biol 20(7):1728-1738. 2025 Jul 18. PMID: 40590393.

[2] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.