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   27-MAR-2024, entry version 168.
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}.
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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; 16.
DR   IntAct; P70318; 28.
DR   MINT; P70318; -.
DR   STRING; 10090.ENSMUSP00000101833; -.
DR   iPTMnet; P70318; -.
DR   PhosphoSitePlus; P70318; -.
DR   EPD; P70318; -.
DR   PaxDb; 10090-ENSMUSP00000101833; -.
DR   PeptideAtlas; P70318; -.
DR   ProteomicsDB; 262779; -.
DR   Pumba; P70318; -.
DR   Antibodypedia; 18838; 171 antibodies from 29 providers.
DR   DNASU; 21843; -.
DR   Ensembl; ENSMUST00000106226.9; ENSMUSP00000101833.3; ENSMUSG00000030846.16.
DR   GeneID; 21843; -.
DR   KEGG; mmu:21843; -.
DR   UCSC; uc009jyy.1; mouse.
DR   AGR; MGI:107913; -.
DR   CTD; 7073; -.
DR   MGI; MGI:107913; Tial1.
DR   VEuPathDB; HostDB:ENSMUSG00000030846; -.
DR   eggNOG; KOG0148; Eukaryota.
DR   GeneTree; ENSGT00940000160482; -.
DR   InParanoid; P70318; -.
DR   OMA; YDMVVAQ; -.
DR   OrthoDB; 12274at2759; -.
DR   PhylomeDB; P70318; -.
DR   TreeFam; TF312915; -.
DR   BioGRID-ORCS; 21843; 9 hits in 78 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 265 other cell types or tissues.
DR   ExpressionAtlas; P70318; baseline and differential.
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:0005829; C:cytosol; ISO:MGI.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
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:0140517; F:protein-RNA adaptor activity; 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:0035332; P:positive regulation of hippo signaling; ISO:MGI.
DR   GO; GO:2000637; P:positive regulation of miRNA-mediated gene silencing; ISO:MGI.
DR   GO; GO:2000648; P:positive regulation of stem cell proliferation; IMP:MGI.
DR   GO; GO:0017145; P:stem cell division; IMP:MGI.
DR   GO; GO:0072089; P:stem cell proliferation; 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   PANTHER; PTHR48025:SF20; HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN M-RELATED; 1.
DR   PANTHER; PTHR48025; OS02G0815200 PROTEIN; 1.
DR   Pfam; PF00076; RRM_1; 4.
DR   SMART; SM00360; RRM; 3.
DR   SMART; SM00361; RRM_1; 3.
DR   SUPFAM; SSF54928; RNA-binding domain, RBD; 3.
DR   PROSITE; PS50102; RRM; 3.
DR   Genevisible; P70318; MM.
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
//