ID TIAR_MOUSE Reviewed; 392 AA. AC P70318; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1997, sequence version 1. DT 25-MAY-2022, entry version 158. DE RecName: Full=Nucleolysin TIAR; DE AltName: Full=TIA-1-related protein; GN Name=Tial1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=8871565; DOI=10.1093/nar/24.19.3829; RA Beck A.R.P., Medley O.G., O'Brien S., Anderson P., Streuli M.; RT "Structure, tissue distribution and genomic organization of the murine RRM- RT type RNA binding proteins TIA-1 and TIAR."; RL Nucleic Acids Res. 24:3829-3836(1996). RN [2] RP FUNCTION. RX PubMed=11514562; DOI=10.1074/jbc.m105642200; RA Le Guiner C., Lejeune F., Galiana D., Kister L., Breathnach R., RA Stevenin J., Del Gatto-Konczak F.; RT "TIA-1 and TIAR activate splicing of alternative exons with weak 5' splice RT sites followed by a U-rich stretch on their own pre-mRNAs."; RL J. Biol. Chem. 276:40638-40646(2001). RN [3] RP SUBCELLULAR LOCATION, DOMAIN, AND MUTAGENESIS OF 117-PHE--ASP-121; RP 156-GLY--ASP-160; 225-TYR--ILE-229; 258-GLY--ASP-264 AND 293-LYS--LYS-300. RX PubMed=16278295; DOI=10.1242/jcs.02669; RA Zhang T., Delestienne N., Huez G., Kruys V., Gueydan C.; RT "Identification of the sequence determinants mediating the nucleo- RT cytoplasmic shuttling of TIAR and TIA-1 RNA-binding proteins."; RL J. Cell Sci. 118:5453-5463(2005). RN [4] RP FUNCTION. RX PubMed=17488725; DOI=10.1074/jbc.m700688200; RA Izquierdo J.M., Valcarcel J.; RT "Two isoforms of the T-cell intracellular antigen 1 (TIA-1) splicing factor RT display distinct splicing regulation activities. Control of TIA-1 isoform RT ratio by TIA-1-related protein."; RL J. Biol. Chem. 282:19410-19417(2007). RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Brain, Lung, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). RN [6] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=19861488; DOI=10.1530/rep-09-0373; RA Yamaji M., Tanaka T., Shigeta M., Chuma S., Saga Y., Saitou M.; RT "Functional reconstruction of NANOS3 expression in the germ cell lineage by RT a novel transgenic reporter reveals distinct subcellular localizations of RT NANOS3."; RL Reproduction 139:381-393(2010). CC -!- FUNCTION: RNA-binding protein involved in alternative pre-RNA splicing CC and in cytoplasmic stress granules formation (By similarity). Shows a CC preference for uridine-rich RNAs (By similarity). Activates splicing of CC alternative exons with weak 5' splice sites followed by a U-rich CC stretch on its own pre-mRNA and on TIA1 mRNA (PubMed:11514562). CC Promotes the inclusion of TIA1 exon 5 to give rise to the long isoform CC (isoform a) of TIA1 (PubMed:17488725). Acts downstream of the stress- CC induced phosphorylation of EIF2S1/EIF2A to promote the recruitment of CC untranslated mRNAs to cytoplasmic stress granules (SG) (By similarity). CC Possesses nucleolytic activity against cytotoxic lymphocyte target CC cells (By similarity). May be involved in apoptosis (By similarity). CC {ECO:0000250|UniProtKB:Q01085, ECO:0000269|PubMed:11514562, CC ECO:0000269|PubMed:17488725}. CC -!- SUBUNIT: Interacts with FASTK. {ECO:0000250|UniProtKB:Q01085}. CC -!- INTERACTION: CC P70318; Q8K2L4: Ddx21; NbExp=2; IntAct=EBI-299820, EBI-7977861; CC P70318; Q3THB3: Hnrnpm; NbExp=2; IntAct=EBI-299820, EBI-4282050; CC P70318; Q6PDM2: Srsf1; NbExp=3; IntAct=EBI-299820, EBI-2550360; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16278295, CC ECO:0000269|PubMed:19861488}. Cytoplasm {ECO:0000269|PubMed:16278295, CC ECO:0000269|PubMed:19861488}. Cytoplasm, Stress granule CC {ECO:0000269|PubMed:19861488}. Cytolytic granule CC {ECO:0000250|UniProtKB:Q01085}. Note=Nuclear import seems to be coupled CC to RNA polymerase II transcription and may be dependent on RNA-binding CC (PubMed:16278295). Accumulates in cytoplasmic stress granules (SG) CC following cellular damage (By similarity). CC {ECO:0000250|UniProtKB:Q01085, ECO:0000269|PubMed:16278295}. CC -!- TISSUE SPECIFICITY: Expressed both in primordial germ cells (PGCs) and CC in neighboring somatic cells. {ECO:0000269|PubMed:19861488}. CC -!- DOMAIN: The RRM 2 domain is required for the binding to target RNA, and CC the RRM 1 and RRM 3 domains seem to contribute to the affinity of the CC interaction with RNA. {ECO:0000250|UniProtKB:Q01085}. CC -!- DOMAIN: The RRM2 domain and the C-terminal residues 290-339 contribute CC to nuclear localization. {ECO:0000269|PubMed:16278295}. CC -!- DOMAIN: The RRM3 domain mediates nuclear export and cytoplasmic CC localization in a manner dependent on RNA- binding. CC {ECO:0000269|PubMed:16278295}. CC -!- PTM: Phosphorylated by MAPK14 following DNA damage, releasing TIAR from CC GADD45A mRNA. {ECO:0000250}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U55861; AAC52870.1; -; mRNA. DR CCDS; CCDS21897.1; -. DR PIR; S72436; S72436. DR RefSeq; NP_033409.1; NM_009383.2. DR AlphaFoldDB; P70318; -. DR SMR; P70318; -. DR BioGRID; 204192; 14. DR IntAct; P70318; 28. DR MINT; P70318; -. DR STRING; 10090.ENSMUSP00000101833; -. DR iPTMnet; P70318; -. DR PhosphoSitePlus; P70318; -. DR EPD; P70318; -. DR PaxDb; P70318; -. DR PeptideAtlas; P70318; -. DR PRIDE; P70318; -. DR ProteomicsDB; 262779; -. DR Antibodypedia; 18838; 147 antibodies from 29 providers. DR DNASU; 21843; -. DR Ensembl; ENSMUST00000106226; ENSMUSP00000101833; ENSMUSG00000030846. DR GeneID; 21843; -. DR KEGG; mmu:21843; -. DR UCSC; uc009jyy.1; mouse. DR CTD; 7073; -. DR MGI; MGI:107913; Tial1. DR VEuPathDB; HostDB:ENSMUSG00000030846; -. DR eggNOG; KOG0148; Eukaryota. DR GeneTree; ENSGT00940000160482; -. DR InParanoid; P70318; -. DR OMA; TETRFQS; -. DR OrthoDB; 1066369at2759; -. DR PhylomeDB; P70318; -. DR TreeFam; TF312915; -. DR Reactome; R-MMU-6803529; FGFR2 alternative splicing. DR BioGRID-ORCS; 21843; 9 hits in 73 CRISPR screens. DR ChiTaRS; Tial1; mouse. DR PRO; PR:P70318; -. DR Proteomes; UP000000589; Chromosome 7. DR RNAct; P70318; protein. DR Bgee; ENSMUSG00000030846; Expressed in ureter smooth muscle and 319 other tissues. DR Genevisible; P70318; MM. DR GO; GO:0044194; C:cytolytic granule; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:1990904; C:ribonucleoprotein complex; ISO:MGI. DR GO; GO:0003677; F:DNA binding; IEA:InterPro. DR GO; GO:0035925; F:mRNA 3'-UTR AU-rich region binding; IDA:MGI. DR GO; GO:0003730; F:mRNA 3'-UTR binding; ISO:MGI. DR GO; GO:1903231; F:mRNA binding involved in posttranscriptional gene silencing; ISO:MGI. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0007281; P:germ cell development; IMP:MGI. DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:MGI. DR GO; GO:2000637; P:positive regulation of gene silencing by miRNA; ISO:MGI. DR GO; GO:0035332; P:positive regulation of hippo signaling; ISO:MGI. DR GO; GO:0017145; P:stem cell division; IMP:MGI. DR CDD; cd12616; RRM1_TIAR; 1. DR CDD; cd12617; RRM2_TIAR; 1. DR CDD; cd12620; RRM3_TIAR; 1. DR Gene3D; 3.30.70.330; -; 3. DR InterPro; IPR012677; Nucleotide-bd_a/b_plait_sf. DR InterPro; IPR035979; RBD_domain_sf. DR InterPro; IPR000504; RRM_dom. DR InterPro; IPR003954; RRM_dom_euk. DR InterPro; IPR034492; TIAR_RRM1. DR InterPro; IPR034494; TIAR_RRM2. DR InterPro; IPR034496; TIAR_RRM3. DR Pfam; PF00076; RRM_1; 4. DR SMART; SM00360; RRM; 3. DR SMART; SM00361; RRM_1; 3. DR SUPFAM; SSF54928; SSF54928; 3. DR PROSITE; PS50102; RRM; 3. PE 1: Evidence at protein level; KW Acetylation; Apoptosis; Cytoplasm; Lysosome; Nucleus; Phosphoprotein; KW Reference proteome; Repeat; RNA-binding. FT CHAIN 1..392 FT /note="Nucleolysin TIAR" FT /id="PRO_0000081979" FT DOMAIN 9..102 FT /note="RRM 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176" FT DOMAIN 114..192 FT /note="RRM 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176" FT DOMAIN 222..294 FT /note="RRM 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176" FT REGION 363..392 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 139 FT /note="N6-acetyllysine" FT /evidence="ECO:0000250|UniProtKB:Q01085" FT MOD_RES 218 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q01085" FT MUTAGEN 117..121 FT /note="FVGDL->DVPDD: Impairs nuclear localization." FT /evidence="ECO:0000269|PubMed:16278295" FT MUTAGEN 156..160 FT /note="GYGFV->PDGDE: Impairs nuclear localization." FT /evidence="ECO:0000269|PubMed:16278295" FT MUTAGEN 225..229 FT /note="YCGGI->DRPPD: Abolishes nuclear export." FT /evidence="ECO:0000269|PubMed:16278295" FT MUTAGEN 258..264 FT /note="GYSFVRF->PDSDERD: Abolishes nuclear export." FT /evidence="ECO:0000269|PubMed:16278295" FT MUTAGEN 293..300 FT /note="KESPDMTK->RESPDMTR: No effect on nuclear FT localization." FT /evidence="ECO:0000269|PubMed:16278295" SQ SEQUENCE 392 AA; 43389 MW; 66E6AF14B9EBE77A CRC64; MMEDDGQPRT LYVGNLSRDV TEVLILQLFS QIGPCKSCKM ITEQPDSRRV NSSVGFSVLQ HTSNDPYCFV EFYEHRDAAA ALAAMNGRKI LGKEVKVNWA TTPSSQKKDT SNHFHVFVGD LSPEITTEDI KSAFAPFGKI SDARVVKDMA TGKSKGYGFV SFYNKLDAEN AIVHMGGQWL GGRQIRTNWA TRKPPAPKST QETNTKQLRF EDVVNQSSPK NCTVYCGGIA SGLTDQLMRQ TFSPFGQIME IRVFPEKGYS FVRFSTHESA AHAIVSVNGT TIEGHVVKCY WGKESPDMTK NFQQVDYSQW GQWSQVYGNP QQYGQYMANG WQVPPYGVYG QPWNQQGFGV DQSPSAAWMG GFGAQPPQGQ APPPVIPPPN QAGYGMASFP TQ //