TIA1_MOUSE
ID TIA1_MOUSE Reviewed; 386 AA.
AC P52912;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 165.
DE RecName: Full=Cytotoxic granule associated RNA binding protein TIA1 {ECO:0000312|MGI:MGI:107914};
DE AltName: Full=Nucleolysin TIA-1 {ECO:0000305};
DE AltName: Full=RNA-binding protein TIA-1;
DE AltName: Full=T-cell-restricted intracellular antigen-1;
DE Short=TIA-1;
GN Name=Tia1; Synonyms=Tia;
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].
RC TISSUE=Blood;
RX PubMed=8759725;
RA Lowin B., French L., Martinou J.-C., Tschopp J.;
RT "Expression of the CTL-associated protein TIA-1 during murine
RT embryogenesis.";
RL J. Immunol. 157:1448-1454(1996).
RN [2]
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 [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Spleen;
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 [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=10921895; DOI=10.1093/emboj/19.15.4154;
RA Piecyk M., Wax S., Beck A.R., Kedersha N., Gupta M., Maritim B., Chen S.,
RA Gueydan C., Kruys V., Streuli M., Anderson P.;
RT "TIA-1 is a translational silencer that selectively regulates the
RT expression of TNF-alpha.";
RL EMBO J. 19:4154-4163(2000).
RN [5]
RP FUNCTION.
RX PubMed=10938105; DOI=10.1128/mcb.20.17.6287-6299.2000;
RA Del Gatto-Konczak F., Bourgeois C.F., Le Guiner C., Kister L., Gesnel M.C.,
RA Stevenin J., Breathnach R.;
RT "The RNA-binding protein TIA-1 is a novel mammalian splicing regulator
RT acting through intron sequences adjacent to a 5' splice site.";
RL Mol. Cell. Biol. 20:6287-6299(2000).
RN [6]
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 [7]
RP SUBCELLULAR LOCATION, AND DOMAIN.
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 [8]
RP FUNCTION.
RX PubMed=16227602; DOI=10.1128/mcb.25.21.9520-9531.2005;
RA Lopez de Silanes I., Galban S., Martindale J.L., Yang X.,
RA Mazan-Mamczarz K., Indig F.E., Falco G., Zhan M., Gorospe M.;
RT "Identification and functional outcome of mRNAs associated with RNA-binding
RT protein TIA-1.";
RL Mol. Cell. Biol. 25:9520-9531(2005).
RN [9]
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=29298433; DOI=10.1016/j.celrep.2017.12.036;
RA Rayman J.B., Karl K.A., Kandel E.R.;
RT "TIA-1 Self-Multimerization, Phase Separation, and Recruitment into Stress
RT Granules Are Dynamically Regulated by Zn2.";
RL Cell Rep. 22:59-71(2018).
RN [10]
RP STRUCTURE BY NMR OF 104-199.
RG RIKEN structural genomics initiative (RSGI);
RT "Solution structure of the RNA binding domain in cytotoxic granule-
RT associated RNA binding protein 1.";
RL Submitted (SEP-2006) to the PDB data bank.
RN [11]
RP STRUCTURE BY NMR OF 105-199.
RX PubMed=18500819; DOI=10.1021/bi7024723;
RA Kuwasako K., Takahashi M., Tochio N., Abe C., Tsuda K., Inoue M.,
RA Terada T., Shirouzu M., Kobayashi N., Kigawa T., Taguchi S., Tanaka A.,
RA Hayashizaki Y., Guntert P., Muto Y., Yokoyama S.;
RT "Solution structure of the second RNA recognition motif (RRM) domain of
RT murine T cell intracellular antigen-1 (TIA-1) and its RNA recognition
RT mode.";
RL Biochemistry 47:6437-6450(2008).
CC -!- FUNCTION: RNA-binding protein involved in the regulation of alternative
CC pre-RNA splicing and mRNA translation by binding to uridine-rich (U-
CC rich) RNA sequences (PubMed:10938105, PubMed:16227602). Binds to U-rich
CC sequences immediately downstream from a 5' splice sites in a uridine-
CC rich small nuclear ribonucleoprotein (U snRNP)-dependent fashion,
CC thereby modulating alternative pre-RNA splicing (PubMed:10938105).
CC Preferably binds to the U-rich IAS1 sequence in a U1 snRNP-dependent
CC manner; this binding is optimal if a 5' splice site is adjacent to IAS1
CC (PubMed:10938105). Activates the use of heterologous 5' splice sites;
CC the activation depends on the intron sequence downstream from the 5'
CC splice site, with a preference for a downstream U-rich sequence
CC (PubMed:10938105). By interacting with SNRPC/U1-C, promotes recruitment
CC and binding of spliceosomal U1 snRNP to 5' splice sites followed by U-
CC rich sequences, thereby facilitating atypical 5' splice site
CC recognition by U1 snRNP (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 TIAR mRNA (PubMed:11514562). Acts as
CC a modulator of alternative splicing for the apoptotic FAS receptor,
CC thereby promoting apoptosis (By similarity). Binds to the 5' splice
CC site region of FAS intron 5 to promote accumulation of transcripts that
CC include exon 6 at the expense of transcripts in which exon 6 is
CC skipped, thereby leading to the transcription of a membrane-bound
CC apoptotic FAS receptor, which promotes apoptosis (By similarity). Binds
CC to a conserved AU-rich cis element in COL2A1 intron 2 and modulates
CC alternative splicing of COL2A1 exon 2 (By similarity). Also binds to
CC the equivalent AT-rich element in COL2A1 genomic DNA, and may thereby
CC be involved in the regulation of transcription (By similarity).
CC Involved in the repression of mRNA translation by binding to AU-rich
CC elements (AREs) located in mRNA 3' untranslated regions (3' UTRs),
CC including target ARE-bearing mRNAs encoding TNF and PTGS2
CC (PubMed:16227602, PubMed:10921895). Also participates in the cellular
CC response to environmental stress, by acting downstream of the stress-
CC induced phosphorylation of EIF2S1/EIF2A to promote the recruitment of
CC untranslated mRNAs to cytoplasmic stress granules (SGs), leading to
CC stress-induced translational arrest (By similarity). Formation and
CC recruitment to SGs is regulated by Zn(2+) (PubMed:29298433). Possesses
CC nucleolytic activity against cytotoxic lymphocyte target cells (By
CC similarity). {ECO:0000250|UniProtKB:P31483,
CC ECO:0000269|PubMed:10921895, ECO:0000269|PubMed:10938105,
CC ECO:0000269|PubMed:11514562, ECO:0000269|PubMed:16227602,
CC ECO:0000269|PubMed:29298433}.
CC -!- SUBUNIT: Homooligomer; homooligomerization is induced by Zn(2+)
CC (PubMed:29298433). Interacts with FASTK; the interactions leads to its
CC phosphorylation (By similarity). Interacts (via RRM1 and the C-terminal
CC glutamine-rich (Q) sequence) with SNRPC/U1-C (via N-terminus); thereby
CC facilitating spliceosomal U1 snRNP recruitment to 5' splice sites (By
CC similarity). {ECO:0000250|UniProtKB:P31483,
CC ECO:0000269|PubMed:29298433}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16278295}. Cytoplasm
CC {ECO:0000269|PubMed:16278295}. Cytoplasm, Stress granule
CC {ECO:0000269|PubMed:29298433}. Note=Accumulates in cytoplasmic stress
CC granules (SG) following cellular damage (PubMed:29298433). Recruitment
CC to SG is induced by Zn(2+) (PubMed:29298433).
CC {ECO:0000269|PubMed:29298433}.
CC -!- DOMAIN: The RNA recognition motif domains RRM 2 and RRM 3 are necessary
CC and sufficient for binding to uridine-rich target pre-mRNA.
CC {ECO:0000250|UniProtKB:P31483}.
CC -!- DOMAIN: The RRM 1 and RRM 2 domains are required for the localization
CC to stress granules (SGs) and for the recruitment of TIAR1 and poly(A)
CC RNA to SGs in response to stress. {ECO:0000250|UniProtKB:P31483}.
CC -!- DOMAIN: The RRM2 domain and the C-terminal residues 287-340 contribute
CC to nuclear localization. {ECO:0000269|PubMed:16278295}.
CC -!- DOMAIN: The RRM3 domain mediates nuclear export.
CC {ECO:0000269|PubMed:16278295}.
CC -!- DOMAIN: The C-terminal glutamine-rich (Q) sequence in combination with
CC the RRM 1 domain is required for the interaction with SNRPC/U1-C and to
CC facilitate recruitment of spliceosomal U1 snRNP to 5' splice sites.
CC {ECO:0000250|UniProtKB:P31483}.
CC -!- PTM: Phosphorylatedby FASTK; phosphorylation occurs after FAS ligation
CC in FAS-mediated apoptosis and before DNA fragmentation.
CC {ECO:0000250|UniProtKB:P31483}.
CC -!- DISRUPTION PHENOTYPE: 50% lethality between embryonic day 16.5 and 3
CC weeks of age (PubMed:10921895). Surviving mice appear normal and live
CC for around 2 years (PubMed:10921895). Increased production of TNF in
CC macrophages after stimulation with lipopolysaccharides (LPS)
CC (PubMed:10921895). Increased susceptibility to LPS-induced endotoxic
CC shock (PubMed:10921895). {ECO:0000269|PubMed:10921895}.
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DR EMBL; U00689; AAA03711.1; -; mRNA.
DR EMBL; U55862; AAC52871.1; -; mRNA.
DR CCDS; CCDS20312.1; -.
DR PIR; S72435; S72435.
DR RefSeq; NP_035715.1; NM_011585.4.
DR PDB; 2DGO; NMR; -; A=87-199.
DR PDB; 2RNE; NMR; -; A=87-199.
DR PDBsum; 2DGO; -.
DR PDBsum; 2RNE; -.
DR AlphaFoldDB; P52912; -.
DR SMR; P52912; -.
DR BioGRID; 204190; 189.
DR CORUM; P52912; -.
DR IntAct; P52912; 1.
DR MINT; P52912; -.
DR STRING; 10090.ENSMUSP00000093425; -.
DR iPTMnet; P52912; -.
DR PhosphoSitePlus; P52912; -.
DR EPD; P52912; -.
DR PaxDb; P52912; -.
DR PRIDE; P52912; -.
DR ProteomicsDB; 262777; -.
DR Antibodypedia; 16302; 566 antibodies from 43 providers.
DR DNASU; 21841; -.
DR Ensembl; ENSMUST00000095753; ENSMUSP00000093425; ENSMUSG00000071337.
DR GeneID; 21841; -.
DR KEGG; mmu:21841; -.
DR UCSC; uc009crp.2; mouse.
DR CTD; 7072; -.
DR MGI; MGI:107914; Tia1.
DR VEuPathDB; HostDB:ENSMUSG00000071337; -.
DR eggNOG; KOG0148; Eukaryota.
DR GeneTree; ENSGT00940000154962; -.
DR InParanoid; P52912; -.
DR OMA; ESFQNQH; -.
DR OrthoDB; 1066369at2759; -.
DR PhylomeDB; P52912; -.
DR TreeFam; TF312915; -.
DR Reactome; R-MMU-6803529; FGFR2 alternative splicing.
DR BioGRID-ORCS; 21841; 4 hits in 74 CRISPR screens.
DR ChiTaRS; Tia1; mouse.
DR EvolutionaryTrace; P52912; -.
DR PRO; PR:P52912; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; P52912; protein.
DR Bgee; ENSMUSG00000071337; Expressed in rostral migratory stream and 261 other tissues.
DR ExpressionAtlas; P52912; baseline and differential.
DR Genevisible; P52912; MM.
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:0097165; C:nuclear stress granule; IDA: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:0035925; F:mRNA 3'-UTR AU-rich region binding; IDA:MGI.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; IDA:UniProtKB.
DR GO; GO:0003723; F:RNA binding; ISO:MGI.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0001818; P:negative regulation of cytokine production; IMP:MGI.
DR GO; GO:0017148; P:negative regulation of translation; IDA:UniProtKB.
DR GO; GO:1904037; P:positive regulation of epithelial cell apoptotic process; ISO:MGI.
DR GO; GO:1903608; P:protein localization to cytoplasmic stress granule; ISO:MGI.
DR GO; GO:0000381; P:regulation of alternative mRNA splicing, via spliceosome; IDA:UniProtKB.
DR GO; GO:0048024; P:regulation of mRNA splicing, via spliceosome; ISO:MGI.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR GO; GO:0034063; P:stress granule assembly; ISS:UniProtKB.
DR CDD; cd12615; RRM1_TIA1; 1.
DR CDD; cd12618; RRM2_TIA1; 1.
DR CDD; cd12621; RRM3_TIA1; 1.
DR Gene3D; 3.30.70.330; -; 3.
DR IDEAL; IID50284; -.
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; IPR034827; TIA-1_RRM1.
DR InterPro; IPR034830; TIA1_RRM2.
DR InterPro; IPR034832; TIA1_RRM3.
DR Pfam; PF00076; RRM_1; 3.
DR SMART; SM00360; RRM; 3.
DR SMART; SM00361; RRM_1; 3.
DR SUPFAM; SSF54928; SSF54928; 2.
DR PROSITE; PS50102; RRM; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Apoptosis; Cytoplasm; mRNA processing;
KW mRNA splicing; Nucleus; Reference proteome; Repeat; RNA-binding.
FT CHAIN 1..386
FT /note="Cytotoxic granule associated RNA binding protein
FT TIA1"
FT /id="PRO_0000081977"
FT DOMAIN 7..83
FT /note="RRM 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 106..184
FT /note="RRM 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT DOMAIN 214..286
FT /note="RRM 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00176"
FT REGION 355..376
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 355..373
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P31483"
FT STRAND 106..112
FT /evidence="ECO:0007829|PDB:2DGO"
FT HELIX 119..126
FT /evidence="ECO:0007829|PDB:2DGO"
FT HELIX 127..129
FT /evidence="ECO:0007829|PDB:2DGO"
FT STRAND 132..139
FT /evidence="ECO:0007829|PDB:2DGO"
FT TURN 141..143
FT /evidence="ECO:0007829|PDB:2DGO"
FT STRAND 146..156
FT /evidence="ECO:0007829|PDB:2DGO"
FT HELIX 157..166
FT /evidence="ECO:0007829|PDB:2DGO"
FT TURN 167..169
FT /evidence="ECO:0007829|PDB:2DGO"
FT STRAND 178..183
FT /evidence="ECO:0007829|PDB:2DGO"
SQ SEQUENCE 386 AA; 42800 MW; 51BFFE90E046D3AE CRC64;
MEDEMPKTLY VGNLSRDVTE ALILQLFSQI GPCKNCKMIM DTAGNDPYCF VEFHEHRHAA
AALAAMNGRK IMGKEVKVNW ATTPSSQKKD TSSSTVVSTQ RSQDHFHVFV GDLSPEITTE
DIKAAFAPFG RISDARVVKD MATGKSKGYG FVSFFNKWDA ENAIQQMGGQ WLGGRQIRTN
WATRKPPAPK STYESNTKQL SYDEVVSQSS PNNCTVYCGG VTSGLTEQLM RQTFSPFGQI
MEIRVFPDKG YSFVRFSSHE SAAHAIVSVN GTTIEGHVVK CYWGKETLDM INPVQQQNQI
GYPPTYGQWG QWYGNAQQIG QYVPNGWQVP AYGVYGQPWS QQGFNQTQSS APWMGPNYSV
PPPQGQNGSM LPSQPAGYRV AGYETQ
