TIA1_HUMAN
ID TIA1_HUMAN Reviewed; 386 AA.
AC P31483; Q53SS9; Q96B58;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 23-SEP-2008, sequence version 3.
DT 03-AUG-2022, entry version 203.
DE RecName: Full=Cytotoxic granule associated RNA binding protein TIA1 {ECO:0000312|HGNC:HGNC:11802};
DE AltName: Full=Nucleolysin TIA-1 isoform p40 {ECO:0000305};
DE AltName: Full=RNA-binding protein TIA-1;
DE AltName: Full=T-cell-restricted intracellular antigen-1;
DE Short=TIA-1;
DE AltName: Full=p40-TIA-1;
GN Name=TIA1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM SHORT), AND FUNCTION.
RX PubMed=1934064; DOI=10.1016/0092-8674(91)90536-8;
RA Tian Q., Streuli M., Saito H., Schlossman S.F., Anderson P.;
RT "A polyadenylate binding protein localized to the granules of cytolytic
RT lymphocytes induces DNA fragmentation in target cells.";
RL Cell 67:629-639(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING.
RC TISSUE=Leukocyte;
RX PubMed=8176212;
RA Kawakami A., Tian Q., Streuli M., Poe M., Edelhoff S., Disteche C.M.,
RA Anderson P.;
RT "Intron-exon organization and chromosomal localization of the human TIA-1
RT gene.";
RL J. Immunol. 152:4937-4945(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3).
RC TISSUE=Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INTERACTION WITH FASTK, AND PHOSPHORYLATION.
RX PubMed=7544399; DOI=10.1084/jem.182.3.865;
RA Tian Q., Taupin J.-L., Elledge S., Robertson M., Anderson P.;
RT "Fas-activated serine/threonine kinase (FAST) phosphorylates TIA-1 during
RT Fas-mediated apoptosis.";
RL J. Exp. Med. 182:865-874(1995).
RN [7]
RP FUNCTION, DOMAIN, AND RNA BINDING.
RX PubMed=8576255; DOI=10.1074/jbc.271.5.2783;
RA Dember L.M., Kim N.D., Liu K.Q., Anderson P.;
RT "Individual RNA recognition motifs of TIA-1 and TIAR have different RNA
RT binding specificities.";
RL J. Biol. Chem. 271:2783-2788(1996).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, AND DOMAIN.
RX PubMed=10613902; DOI=10.1083/jcb.147.7.1431;
RA Kedersha N.L., Gupta M., Li W., Miller I., Anderson P.;
RT "RNA-binding proteins TIA-1 and TIAR link the phosphorylation of eIF-2
RT alpha to the assembly of mammalian stress granules.";
RL J. Cell Biol. 147:1431-1442(1999).
RN [9]
RP FUNCTION.
RX PubMed=11106748; DOI=10.1016/s1097-2765(00)00107-6;
RA Foerch P., Puig O., Kedersha N., Martinez C., Granneman S., Seraphin B.,
RA Anderson P., Valcarcel J.;
RT "The apoptosis-promoting factor TIA-1 is a regulator of alternative pre-
RT mRNA splicing.";
RL Mol. Cell 6:1089-1098(2000).
RN [10]
RP FUNCTION, INTERACTION WITH SNRPC, DOMAIN, AND RNA BINDING.
RX PubMed=12486009; DOI=10.1093/emboj/cdf668;
RA Foerch P., Puig O., Martinez C., Seraphin B., Valcarcel J.;
RT "The splicing regulator TIA-1 interacts with U1-C to promote U1 snRNP
RT recruitment to 5' splice sites.";
RL EMBO J. 21:6882-6892(2002).
RN [11]
RP FUNCTION.
RX PubMed=14966131; DOI=10.1074/jbc.m313439200;
RA Zuccato E., Buratti E., Stuani C., Baralle F.E., Pagani F.;
RT "An intronic polypyrimidine-rich element downstream of the donor site
RT modulates cystic fibrosis transmembrane conductance regulator exon 9
RT alternative splicing.";
RL J. Biol. Chem. 279:16980-16988(2004).
RN [12]
RP SUBCELLULAR LOCATION.
RX PubMed=15371533; DOI=10.1091/mbc.e04-08-0715;
RA Gilks N., Kedersha N., Ayodele M., Shen L., Stoecklin G., Dember L.M.,
RA Anderson P.;
RT "Stress granule assembly is mediated by prion-like aggregation of TIA-1.";
RL Mol. Biol. Cell 15:5383-5398(2004).
RN [13]
RP INTERACTION WITH FASTK.
RX PubMed=17135269; DOI=10.1074/jbc.c600198200;
RA Izquierdo J.M., Valcarcel J.;
RT "Fas-activated serine/threonine kinase (FAST K) synergizes with TIA-1/TIAR
RT proteins to regulate Fas alternative splicing.";
RL J. Biol. Chem. 282:1539-1543(2007).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
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 [15]
RP FUNCTION.
RX PubMed=17580305; DOI=10.1074/jbc.m702717200;
RA McAlinden A., Liang L., Mukudai Y., Imamura T., Sandell L.J.;
RT "Nuclear protein TIA-1 regulates COL2A1 alternative splicing and interacts
RT with precursor mRNA and genomic DNA.";
RL J. Biol. Chem. 282:24444-24454(2007).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [17]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 105-186, AND SUBCELLULAR
RP LOCATION.
RX PubMed=18201561; DOI=10.1016/j.bbrc.2008.01.027;
RA Kumar A.O., Swenson M.C., Benning M.M., Kielkopf C.L.;
RT "Structure of the central RNA recognition motif of human TIA-1 at 1.95A
RT resolution.";
RL Biochem. Biophys. Res. Commun. 367:813-819(2008).
RN [19]
RP VARIANT WDM LYS-384, AND CHARACTERIZATION OF VARIANT WDM LYS-384.
RX PubMed=23401021; DOI=10.1002/ana.23831;
RA Hackman P., Sarparanta J., Lehtinen S., Vihola A., Evila A., Jonson P.H.,
RA Luque H., Kere J., Screen M., Chinnery P.F., Ahlberg G., Edstrom L.,
RA Udd B.;
RT "Welander distal myopathy is caused by a mutation in the RNA-binding
RT protein TIA1.";
RL Ann. Neurol. 73:500-509(2013).
RN [20]
RP VARIANT WDM LYS-384.
RX PubMed=23348830; DOI=10.1002/humu.22282;
RA Klar J., Sobol M., Melberg A., Maebert K., Ameur A., Johansson A.C.,
RA Feuk L., Entesarian M., Orlen H., Casar-Borota O., Dahl N.;
RT "Welander distal myopathy caused by an ancient founder mutation in TIA1
RT associated with perturbed splicing.";
RL Hum. Mutat. 34:572-577(2013).
RN [21]
RP INVOLVEMENT IN ALS26, VARIANTS ALS26 MET-294; ILE-334; ARG-355; MET-360;
RP LEU-362 AND THR-381, AND CHARACTERIZATION OF VARIANTS ALS26 LEU-362 AND WDM
RP LYS-384.
RX PubMed=28817800; DOI=10.1016/j.neuron.2017.07.025;
RA Mackenzie I.R., Nicholson A.M., Sarkar M., Messing J., Purice M.D.,
RA Pottier C., Annu K., Baker M., Perkerson R.B., Kurti A., Matchett B.J.,
RA Mittag T., Temirov J., Hsiung G.R., Krieger C., Murray M.E., Kato M.,
RA Fryer J.D., Petrucelli L., Zinman L., Weintraub S., Mesulam M., Keith J.,
RA Zivkovic S.A., Hirsch-Reinshagen V., Roos R.P., Zuechner S.,
RA Graff-Radford N.R., Petersen R.C., Caselli R.J., Wszolek Z.K., Finger E.,
RA Lippa C., Lacomis D., Stewart H., Dickson D.W., Kim H.J., Rogaeva E.,
RA Bigio E., Boylan K.B., Taylor J.P., Rademakers R.;
RT "TIA1 Mutations in Amyotrophic Lateral Sclerosis and Frontotemporal
RT Dementia Promote Phase Separation and Alter Stress Granule Dynamics.";
RL Neuron 95:808-816.e9(2017).
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:8576255, PubMed:11106748, PubMed:12486009,
CC PubMed:17488725). Binds to U-rich sequences immediately downstream from
CC a 5' splice sites in a uridine-rich small nuclear ribonucleoprotein (U
CC snRNP)-dependent fashion, thereby modulating alternative pre-RNA
CC splicing (PubMed:11106748, PubMed:8576255). Preferably binds to the U-
CC rich IAS1 sequence in a U1 snRNP-dependent manner; this binding is
CC optimal if a 5' splice site is adjacent to IAS1 (By similarity).
CC Activates the use of heterologous 5' splice sites; the activation
CC depends on the intron sequence downstream from the 5' splice site, with
CC a preference for a downstream U-rich sequence (PubMed:11106748). By
CC interacting with SNRPC/U1-C, promotes recruitment and binding of
CC spliceosomal U1 snRNP to 5' splice sites followed by U-rich sequences,
CC thereby facilitating atypical 5' splice site recognition by U1 snRNP
CC (PubMed:11106748, PubMed:12486009, PubMed:17488725). Activates splicing
CC of alternative exons with weak 5' splice sites followed by a U-rich
CC stretch on its own pre-mRNA and on TIAR mRNA (By similarity). Acts as a
CC modulator of alternative splicing for the apoptotic FAS receptor,
CC thereby promoting apoptosis (PubMed:11106748, PubMed:1934064,
CC PubMed:17488725). Binds to the 5' splice site region of FAS intron 5 to
CC promote accumulation of transcripts that include exon 6 at the expense
CC of transcripts in which exon 6 is skipped, thereby leading to the
CC transcription of a membrane-bound apoptotic FAS receptor, which
CC promotes apoptosis (PubMed:11106748, PubMed:1934064, PubMed:17488725).
CC Binds to a conserved AU-rich cis element in COL2A1 intron 2 and
CC modulates alternative splicing of COL2A1 exon 2 (PubMed:17580305). Also
CC binds to the equivalent AT-rich element in COL2A1 genomic DNA, and may
CC thereby be involved in the regulation of transcription
CC (PubMed:17580305). Binds specifically to a polypyrimidine-rich
CC controlling element (PCE) located between the weak 5' splice site and
CC the intronic splicing silencer of CFTR mRNA to promote exon 9
CC inclusion, thereby antagonizing PTB1 and its role in exon skipping of
CC CFTR exon 9 (PubMed:14966131). Involved in the repression of mRNA
CC translation by binding to AU-rich elements (AREs) located in mRNA 3'
CC untranslated regions (3' UTRs), including target ARE-bearing mRNAs
CC encoding TNF and PTGS2 (By similarity). Also participates in the
CC cellular response to environmental stress, by acting downstream of the
CC stress-induced phosphorylation of EIF2S1/EIF2A to promote the
CC recruitment of untranslated mRNAs to cytoplasmic stress granules (SGs),
CC leading to stress-induced translational arrest (PubMed:10613902).
CC Formation and recruitment to SGs is regulated by Zn(2+) (By
CC similarity). Possesses nucleolytic activity against cytotoxic
CC lymphocyte target cells (PubMed:1934064).
CC {ECO:0000250|UniProtKB:P52912, ECO:0000269|PubMed:10613902,
CC ECO:0000269|PubMed:11106748, ECO:0000269|PubMed:12486009,
CC ECO:0000269|PubMed:14966131, ECO:0000269|PubMed:17488725,
CC ECO:0000269|PubMed:17580305, ECO:0000269|PubMed:1934064,
CC ECO:0000269|PubMed:8576255}.
CC -!- FUNCTION: [Isoform Short]: Displays enhanced splicing regulatory
CC activity compared with TIA isoform Long. {ECO:0000269|PubMed:17488725}.
CC -!- SUBUNIT: Homooligomer; homooligomerization is induced by Zn(2+) (By
CC similarity). Interacts with FASTK; the interactions leads to its
CC phosphorylation (PubMed:7544399, PubMed:17135269). Interacts (via RRM1
CC and the C-terminal glutamine-rich (Q) sequence) with SNRPC/U1-C (via N-
CC terminus); thereby facilitating spliceosomal U1 snRNP recruitment to 5'
CC splice sites (PubMed:12486009). {ECO:0000250|UniProtKB:P52912,
CC ECO:0000269|PubMed:12486009, ECO:0000269|PubMed:17135269,
CC ECO:0000269|PubMed:7544399}.
CC -!- INTERACTION:
CC P31483; P08621: SNRNP70; NbExp=2; IntAct=EBI-1387216, EBI-1049228;
CC P31483; P09012: SNRPA; NbExp=4; IntAct=EBI-1387216, EBI-607085;
CC P31483; P09234: SNRPC; NbExp=6; IntAct=EBI-1387216, EBI-766589;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10613902,
CC ECO:0000269|PubMed:15371533, ECO:0000305|PubMed:18201561}. Cytoplasm
CC {ECO:0000269|PubMed:17488725}. Cytoplasm, Stress granule
CC {ECO:0000250|UniProtKB:P52912, ECO:0000269|PubMed:10613902,
CC ECO:0000269|PubMed:15371533}. Note=Accumulates in cytoplasmic stress
CC granules (SG) following cellular damage (PubMed:15371533,
CC PubMed:10613902). Recruitment to SG is induced by Zn(2+) (By
CC similarity). {ECO:0000250|UniProtKB:P52912,
CC ECO:0000269|PubMed:10613902, ECO:0000269|PubMed:15371533}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=Long; Synonyms=a {ECO:0000303|PubMed:17488725};
CC IsoId=P31483-1; Sequence=Displayed;
CC Name=Short; Synonyms=b {ECO:0000303|PubMed:17488725};
CC IsoId=P31483-2; Sequence=VSP_005892;
CC Name=3;
CC IsoId=P31483-3; Sequence=VSP_057403, VSP_057404;
CC -!- TISSUE SPECIFICITY: Expressed in heart, small intestine, kidney, liver,
CC lung, skeletal muscle, testes, pancreas, and ovary (at protein level).
CC {ECO:0000269|PubMed:17488725}.
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:0000269|PubMed:12486009, ECO:0000269|PubMed:8576255}.
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:0000269|PubMed:10613902}.
CC -!- DOMAIN: The RRM2 domain and the C-terminal residues 287-340 contribute
CC to nuclear localization. {ECO:0000250|UniProtKB:P52912}.
CC -!- DOMAIN: The RRM3 domain mediates nuclear export.
CC {ECO:0000250|UniProtKB:P52912}.
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:0000269|PubMed:12486009}.
CC -!- PTM: Phosphorylated by FASTK; phosphorylation occurs after FAS ligation
CC in FAS-mediated apoptosis and before DNA fragmentation.
CC {ECO:0000269|PubMed:7544399}.
CC -!- DISEASE: Welander distal myopathy (WDM) [MIM:604454]: An autosomal
CC dominant disorder characterized by adult onset of distal muscle
CC weakness predominantly affecting the distal long extensors of the
CC hands, with slow progression to involve all small hand muscles and the
CC lower legs. Skeletal muscle biopsy shows myopathic changes and
CC prominent rimmed vacuoles. Rare homozygous patients showed earlier
CC onset, faster progression, and proximal muscle involvement.
CC {ECO:0000269|PubMed:23348830, ECO:0000269|PubMed:23401021}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Amyotrophic lateral sclerosis 26, with or without
CC frontotemporal dementia (ALS26) [MIM:619133]: A form of amyotrophic
CC lateral sclerosis, a neurodegenerative disorder affecting upper motor
CC neurons in the brain and lower motor neurons in the brain stem and
CC spinal cord, resulting in fatal paralysis. Sensory abnormalities are
CC absent. The pathologic hallmarks of the disease include pallor of the
CC corticospinal tract due to loss of motor neurons, presence of
CC ubiquitin-positive inclusions within surviving motor neurons, and
CC deposition of pathologic aggregates. The etiology of amyotrophic
CC lateral sclerosis is likely to be multifactorial, involving both
CC genetic and environmental factors. The disease is inherited in 5-10% of
CC the cases. ALS26 inheritance is autosomal dominant. Some patients may
CC develop frontotemporal dementia. {ECO:0000269|PubMed:28817800}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
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DR EMBL; M77142; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; S70114; AAD14053.1; -; Genomic_DNA.
DR EMBL; AC016700; AAX93193.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99824.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99826.1; -; Genomic_DNA.
DR EMBL; CH471053; EAW99827.1; -; Genomic_DNA.
DR EMBL; BC015944; AAH15944.1; -; mRNA.
DR CCDS; CCDS1900.1; -. [P31483-2]
DR CCDS; CCDS1901.1; -. [P31483-1]
DR CCDS; CCDS86846.1; -. [P31483-3]
DR PIR; A39293; A39293.
DR RefSeq; NP_071320.2; NM_022037.2. [P31483-2]
DR RefSeq; NP_071505.2; NM_022173.2. [P31483-1]
DR PDB; 2MJN; NMR; -; A=105-285.
DR PDB; 3BS9; X-ray; 1.95 A; A/B=105-186.
DR PDB; 5ITH; X-ray; 2.31 A; A=105-194.
DR PDB; 5O2V; NMR; -; A=1-92.
DR PDB; 5O3J; X-ray; 2.97 A; A=104-181.
DR PDB; 6ELD; X-ray; 2.48 A; A=1-92.
DR PDBsum; 2MJN; -.
DR PDBsum; 3BS9; -.
DR PDBsum; 5ITH; -.
DR PDBsum; 5O2V; -.
DR PDBsum; 5O3J; -.
DR PDBsum; 6ELD; -.
DR AlphaFoldDB; P31483; -.
DR SASBDB; P31483; -.
DR SMR; P31483; -.
DR BioGRID; 112928; 82.
DR IntAct; P31483; 44.
DR MINT; P31483; -.
DR STRING; 9606.ENSP00000401371; -.
DR iPTMnet; P31483; -.
DR MetOSite; P31483; -.
DR PhosphoSitePlus; P31483; -.
DR BioMuta; TIA1; -.
DR DMDM; 206729905; -.
DR CPTAC; CPTAC-1645; -.
DR EPD; P31483; -.
DR jPOST; P31483; -.
DR MassIVE; P31483; -.
DR MaxQB; P31483; -.
DR PaxDb; P31483; -.
DR PeptideAtlas; P31483; -.
DR PRIDE; P31483; -.
DR ProteomicsDB; 54790; -. [P31483-1]
DR ProteomicsDB; 54791; -. [P31483-2]
DR ProteomicsDB; 76048; -.
DR Antibodypedia; 16302; 566 antibodies from 43 providers.
DR DNASU; 7072; -.
DR Ensembl; ENST00000415783.6; ENSP00000404023.2; ENSG00000116001.17. [P31483-2]
DR Ensembl; ENST00000416149.6; ENSP00000413751.2; ENSG00000116001.17. [P31483-3]
DR Ensembl; ENST00000433529.7; ENSP00000401371.2; ENSG00000116001.17. [P31483-1]
DR GeneID; 7072; -.
DR KEGG; hsa:7072; -.
DR MANE-Select; ENST00000433529.7; ENSP00000401371.2; NM_022173.4; NP_071505.2.
DR UCSC; uc002sgj.5; human. [P31483-1]
DR UCSC; uc002sgm.4; human.
DR CTD; 7072; -.
DR DisGeNET; 7072; -.
DR GeneCards; TIA1; -.
DR HGNC; HGNC:11802; TIA1.
DR HPA; ENSG00000116001; Low tissue specificity.
DR MalaCards; TIA1; -.
DR MIM; 603518; gene.
DR MIM; 604454; phenotype.
DR MIM; 619133; phenotype.
DR neXtProt; NX_P31483; -.
DR OpenTargets; ENSG00000116001; -.
DR Orphanet; 603; Distal myopathy, Welander type.
DR PharmGKB; PA36511; -.
DR VEuPathDB; HostDB:ENSG00000116001; -.
DR eggNOG; KOG0148; Eukaryota.
DR GeneTree; ENSGT00940000154962; -.
DR HOGENOM; CLU_012062_15_6_1; -.
DR InParanoid; P31483; -.
DR OMA; ESFQNQH; -.
DR OrthoDB; 1066369at2759; -.
DR PhylomeDB; P31483; -.
DR TreeFam; TF312915; -.
DR PathwayCommons; P31483; -.
DR Reactome; R-HSA-6803529; FGFR2 alternative splicing.
DR SignaLink; P31483; -.
DR BioGRID-ORCS; 7072; 20 hits in 1078 CRISPR screens.
DR ChiTaRS; TIA1; human.
DR EvolutionaryTrace; P31483; -.
DR GenomeRNAi; 7072; -.
DR Pharos; P31483; Tbio.
DR PRO; PR:P31483; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; P31483; protein.
DR Bgee; ENSG00000116001; Expressed in right uterine tube and 202 other tissues.
DR ExpressionAtlas; P31483; baseline and differential.
DR Genevisible; P31483; HS.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0010494; C:cytoplasmic stress granule; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0097165; C:nuclear stress granule; IDA:MGI.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0035925; F:mRNA 3'-UTR AU-rich region binding; IEA:Ensembl.
DR GO; GO:0003730; F:mRNA 3'-UTR binding; ISS:UniProtKB.
DR GO; GO:0008143; F:poly(A) binding; TAS:ProtInc.
DR GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; TAS:ProtInc.
DR GO; GO:0006397; P:mRNA processing; IEA:UniProtKB-KW.
DR GO; GO:0001818; P:negative regulation of cytokine production; IEA:Ensembl.
DR GO; GO:0017148; P:negative regulation of translation; ISS:UniProtKB.
DR GO; GO:1903608; P:protein localization to cytoplasmic stress granule; IMP:AgBase.
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; IDA:UniProtKB.
DR GO; GO:0008380; P:RNA splicing; IEA:UniProtKB-KW.
DR GO; GO:0034063; P:stress granule assembly; IDA:UniProtKB.
DR CDD; cd12618; RRM2_TIA1; 1.
DR CDD; cd12621; RRM3_TIA1; 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; 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; 3.
DR PROSITE; PS50102; RRM; 3.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing;
KW Amyotrophic lateral sclerosis; Apoptosis; Cytoplasm; Disease variant;
KW mRNA processing; mRNA splicing; Neurodegeneration; Nucleus;
KW Reference proteome; Repeat; RNA-binding.
FT CHAIN 1..386
FT /note="Cytotoxic granule associated RNA binding protein
FT TIA1"
FT /id="PRO_0000031031"
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 354..386
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 354..374
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT VAR_SEQ 93..104
FT /note="SSTVVSTQRSQD -> N (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:1934064"
FT /id="VSP_005892"
FT VAR_SEQ 195..214
FT /note="SNTKQLSYDEVVNQSSPSNC -> CRCIGEEKEMWNFGEKYARF (in
FT isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_057403"
FT VAR_SEQ 215..386
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_057404"
FT VARIANT 294
FT /note="V -> M (in ALS26; unknown pathological significance;
FT dbSNP:rs144296151)"
FT /evidence="ECO:0000269|PubMed:28817800"
FT /id="VAR_085357"
FT VARIANT 334
FT /note="M -> I (in ALS26; unknown pathological significance;
FT dbSNP:rs747006488)"
FT /evidence="ECO:0000269|PubMed:28817800"
FT /id="VAR_085358"
FT VARIANT 355
FT /note="G -> R (in ALS26; unknown pathological significance;
FT dbSNP:rs372889101)"
FT /evidence="ECO:0000269|PubMed:28817800"
FT /id="VAR_085359"
FT VARIANT 360
FT /note="V -> M (in ALS26; unknown pathological significance;
FT dbSNP:rs201905164)"
FT /evidence="ECO:0000269|PubMed:28817800"
FT /id="VAR_085360"
FT VARIANT 362
FT /note="P -> L (in ALS26; accelerated formation of TIA1
FT amyloid-like fibrils; impaired stress granule disassembly;
FT accumulation of insoluble TARDBP/TDP43-positive stress
FT granules; dbSNP:rs757332023)"
FT /evidence="ECO:0000269|PubMed:28817800"
FT /id="VAR_085361"
FT VARIANT 381
FT /note="A -> T (in ALS26; unknown pathological significance;
FT dbSNP:rs768554955)"
FT /evidence="ECO:0000269|PubMed:28817800"
FT /id="VAR_085362"
FT VARIANT 384
FT /note="E -> K (in WDM; results in a mild increase of stress
FT granule numbers compared to controls; impaired stress
FT granule disassembly; dbSNP:rs747068278)"
FT /evidence="ECO:0000269|PubMed:23348830,
FT ECO:0000269|PubMed:23401021, ECO:0000269|PubMed:28817800"
FT /id="VAR_069897"
FT CONFLICT 116
FT /note="E -> Q (in Ref. 1; M77142)"
FT /evidence="ECO:0000305"
FT HELIX 2..4
FT /evidence="ECO:0007829|PDB:5O2V"
FT STRAND 8..13
FT /evidence="ECO:0007829|PDB:6ELD"
FT HELIX 20..28
FT /evidence="ECO:0007829|PDB:6ELD"
FT STRAND 33..39
FT /evidence="ECO:0007829|PDB:6ELD"
FT STRAND 42..44
FT /evidence="ECO:0007829|PDB:5O2V"
FT STRAND 48..55
FT /evidence="ECO:0007829|PDB:6ELD"
FT HELIX 56..66
FT /evidence="ECO:0007829|PDB:6ELD"
FT STRAND 70..75
FT /evidence="ECO:0007829|PDB:6ELD"
FT STRAND 77..82
FT /evidence="ECO:0007829|PDB:6ELD"
FT STRAND 106..112
FT /evidence="ECO:0007829|PDB:3BS9"
FT HELIX 119..126
FT /evidence="ECO:0007829|PDB:3BS9"
FT HELIX 127..129
FT /evidence="ECO:0007829|PDB:3BS9"
FT STRAND 132..139
FT /evidence="ECO:0007829|PDB:3BS9"
FT TURN 141..143
FT /evidence="ECO:0007829|PDB:3BS9"
FT STRAND 146..156
FT /evidence="ECO:0007829|PDB:3BS9"
FT HELIX 157..167
FT /evidence="ECO:0007829|PDB:3BS9"
FT STRAND 171..176
FT /evidence="ECO:0007829|PDB:5O3J"
FT STRAND 178..182
FT /evidence="ECO:0007829|PDB:3BS9"
FT HELIX 202..206
FT /evidence="ECO:0007829|PDB:2MJN"
FT STRAND 215..219
FT /evidence="ECO:0007829|PDB:2MJN"
FT HELIX 227..234
FT /evidence="ECO:0007829|PDB:2MJN"
FT TURN 235..237
FT /evidence="ECO:0007829|PDB:2MJN"
FT STRAND 240..246
FT /evidence="ECO:0007829|PDB:2MJN"
FT TURN 247..250
FT /evidence="ECO:0007829|PDB:2MJN"
FT STRAND 251..258
FT /evidence="ECO:0007829|PDB:2MJN"
FT HELIX 259..269
FT /evidence="ECO:0007829|PDB:2MJN"
FT STRAND 280..283
FT /evidence="ECO:0007829|PDB:2MJN"
SQ SEQUENCE 386 AA; 42963 MW; 4FD2E8B7AF57A0D6 CRC64;
MEDEMPKTLY VGNLSRDVTE ALILQLFSQI GPCKNCKMIM DTAGNDPYCF VEFHEHRHAA
AALAAMNGRK IMGKEVKVNW ATTPSSQKKD TSSSTVVSTQ RSQDHFHVFV GDLSPEITTE
DIKAAFAPFG RISDARVVKD MATGKSKGYG FVSFFNKWDA ENAIQQMGGQ WLGGRQIRTN
WATRKPPAPK STYESNTKQL SYDEVVNQSS PSNCTVYCGG VTSGLTEQLM RQTFSPFGQI
MEIRVFPDKG YSFVRFNSHE SAAHAIVSVN GTTIEGHVVK CYWGKETLDM INPVQQQNQI
GYPQPYGQWG QWYGNAQQIG QYMPNGWQVP AYGMYGQAWN QQGFNQTQSS APWMGPNYGV
QPPQGQNGSM LPNQPSGYRV AGYETQ
