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FLASH GENE

Symbol

TIA1

contributors: mct - updated : 29-08-2023

HGNC name	TIA1 cytotoxic granule-associated RNA binding protein
HGNC id	11802

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	ALS26 amyotrophic lateral sclerosis 26 with or without frontotemporal dementia WDM Welander distal myopathy
Location	2p13.3      Physical location : 70.436.576 - 70.475.779
Synonym name	T-cell-restricted intracellular antigen-1
	cytotoxic granule-associated RNA-binding protein
	p40-TIA-1 (containing p15-TIA-1)
Synonym symbol(s)	TIA-1, ALS26, WDM

DNA

TYPE	functioning gene
STRUCTURE	39.35 kb     12 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Binding site
motif	repetitive sequence   other
text structure	Au rich element (ARE) in 3'utr

MAPPING

cloned

Y

linked

status

confirmed

regionally located

in the PARK3 region

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_022037 12 splicing 2357 40 375 - 2022 35163320 short isoform 1 lacking exon 5 NM_022173 13 splicing 4653 42.9 386 - 2022 35163320 long isoform 2 NM_001351513 12 - 4508 NP_001338442 - 338 - 2022 35163320 NM_001351514 11 - 4504 NP_001338443 - 310 - 2022 35163320 NM_001351511 13 - 4541 NP_001338440 - 349 - 2022 35163320 NM_001351524 13 - 4629 NP_001338453 - 246 - 2022 35163320 NM_001351517 15 - 4849 NP_001338446 - 245 - 2022 35163320 NM_001351510 15 - 4598 NP_001338439 - 374 - 2022 35163320 NM_001351525 13 - 4667 NP_001338454 - 246 - 2022 35163320 NM_001351515 13 - 4720 NP_001338444 - 285 - 2022 35163320 NM_001351508 13 - 4631 NP_001338437 - 385 - 2022 35163320 NM_001351509 12 - 4607 NP_001338438 - 377 - 2022 35163320 NM_001351512 13 - 4514 NP_001338441 - 340 - 2022 35163320 NM_001351516 11 - 1053 NP_001338445 - 255 - 2022 35163320 NM_001351518 8 - 995 NP_001338447 - 214 - 2022 35163320 NM_001351519 7 - 802 NP_001338448 - 171 - 2022 35163320 NM_001351520 8 - 927 NP_001338449 - 163 - 2022 35163320 NM_001351521 6 - 769 NP_001338450 - 160 - 2022 35163320 NM_001351522 8 - 868 NP_001338451 - 144 - 2022 35163320 NM_001351523 5 - 672 NP_001338452 - 95 - 2022 35163320

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive mouth tongue     highly Hearing/Equilibrium ear       highly   ear inner cochlea   highly Lymphoid/Immune lymph node       highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Connective adipose     highly

cells

System Cell Pubmed Species Stage Rna symbol Lymphoid/Immune lymphocyte

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	three N-terminal RNA recognition motifs (RRMs), and any one RRM in combination with a Q domain is necessary and sufficient for TIA1-associated regulation of SMN2 exon 7 splicing
	a prion-related domain
	a C-terminal glutamine-rich (Q-rich) domain

isoforms

Precursor

p40-TIA1, precursor of a 15 kDa (p15-TIA-1) protein

HOMOLOGY

interspecies	homolog to murine Tia1
	homolog to rattus LOC312510

intraspecies

paralog to TIAL1

Homologene

FAMILY

U-rich element mRNA-binding protein family

CATEGORY

RNA associated

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic,granule
	intracellular,nucleus,nucleoplasm
text	also colocalizing with POLR in stress granules, initiated by the phosphorylayion of EIF2A
	subcellular nucleo-cytoplasmic localization

basic FUNCTION	cytotoxic granule associated RNA binding protein
	regulator of alternative pre-mRNA splicing
	may be involved in induction of apoptosis
	may have dual role in shuttling between DNA and RNA ligands to co-regulate COL2A1 expression at the level of transcription and pre-mRNA alternative splicing
	major granule associated species
	translational silencer of COX2, selectively regulating the expression of TNF
	nucleolytic activity against cytotoxic lymphocyte target cells
	acting as a post-transcriptional silencer, and suppressing the production of the TNF-alpha protein
	TIA1, and TIAL1 are mRNA-binding proteins that can aggregate within granules under specific stress conditions
	its expression counteracts the inhibitory effect of polypyrimidine tract binding protein, a ubiquitously expressed factor recently implicated in regulation of SMN exon 7 splicing
	role of TIA1 phosphorylation in autophagy
	TIA1 oxidation inhibits stress granule assembly and sensitizes cells to stress-induced apoptosis
	essential contributions of the TIA1 and TIAL1 to the fidelity of mRNA maturation, translation, and RNA-stress-sensing pathways in human cells
	is an important regulator of the innate immune response in the periphery, dampening cytotoxic inflammation and apoptosis during cellular stress
	likely TIA1 dampens the immune response in the central nervous system during chronic stress
	RNA-binding protein that can regulate splicing, stability, or translation of target mRNAs, and play critical roles in stress response and neurodevelopment
	translation repression is a key process targeted by TIA1 binding which implicate TIA1 function in neuronal differentiation
	TIA1 appears to control the expression of both pro- and anti-tumorigenic factors in hepatic cancer cells
	in pro-B cells, the RNA-binding proteins T cell intracellular antigen 1 (TIA1) and TIA1-like protein (TIAL1) act redundantly to enable developmental progression
	importance of tight regulation of RNA splicing by TIA1 and TIAL1 for the expression of integrative transcriptional programs that control DNA damage sensing and repair during B cell development
	TIA1 and TIAL1 are key players in the post-transcriptional program that selects high-affinity antigen-specific germinal centers (GCs) B cells

CELLULAR PROCESS	cell life, cell death/apoptosis

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA	binding
	poly(A) binding

small molecule

protein	ARE element of TNF
	binding to FASTK
	interacts with a conserved AU-rich cis element in COL2A1 intron 2 and modulates alternative splicing of exon 2
	interacting with RPS6KA3 (the RPS6KA3 N-terminal kinase domain controls the direct interaction with the prion-related domain of TIA1)
	KHDRBS1 complexed with T-cell intracellular antigen-1 (TIA1), a core SG component, and that the complex formation was correlated with stress granules (SG) recruitment
	regulate SMN exon 7 splicing by binding to intron 7 sequences away from the 5prime ss
	TIA1 and TIAL1 proteins are intron-associated positive regulators of SMN2 exon 7 splicing
	ANXA7 is an interaction protein of TIA1

cell & other

REGULATION

Other	regulated by TARDBP (TARDBP contributes to both the assembly and maintenance of stress granules (SGs)in response to oxidative stress and differentially regulates key SGs components, including TIA1 and G3BP1)
	rapid and severe hypoxia caused co-aggregation of TIAL1/TIA1 and these proteins suppressed HIF1A expression

ASSOCIATED DISORDERS

corresponding disease(s)

ALS26 , WDM

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --other   expressed in synovium of patients with rheumatoid arthritis constitutional     --over   in the thyroid tissues in patients with Graves disease tumoral     --low   in hepatocellular carcinoma (HCC)

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	TIA1 is a biomarker in HCC
Therapy target
	System Type Disorder Pubmed cancer digestive liver TIA1 is a therapeutic target in HCC

ANIMAL & CELL MODELS