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FLASH GENE

Symbol

TARBP2

contributors: shn/mct - updated : 28-12-2015

HGNC name	TAR (HIV-1) RNA binding protein 2
HGNC id	11569

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	12q13.13      Physical location : 53.894.704 - 53.900.213
Synonym name	TAR (HIV) RNA binding protein 2
	trans-activation responsive RNA-binding protein
	loquacious, Drosophila, homolog of
Synonym symbol(s)	LOQS, TRBP, TRBP1, TRBP2

DNA

TYPE	functioning gene
STRUCTURE	6.23 kb     9 Exon(s)

10 Kb 5' upstream gene genomic sequence study

regulatory sequence	Promoter (CAAT box)
	cytosine-phosphate-guanine/HTF
	Binding site   transcription factor
text structure	several potential binding sites for transcriptional factors

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - D12S359 - D12S1618 - TARBP2 - D12S1586 - D12S1651 - qter
Authors	Kozak (1995)
Text	TARBP2 gene was mapped to 12p12.1-q13.1 by analysis of somatic cell hybrids

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_134323 9 splicing 1888 NP_599150 39.1 366 - 2014 24563462 two adjacent promoters initiate transcription of alternative first exons NM_134324 9 splicing 1488 NP_599151 - 345 - 2014 24563462 two adjacent promoters initiate transcription of alternative first exons NM_004178 9 - 1448 NP_004169 - 345 - 2014 24563462

EXPRESSION

Type

widely

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 blood / hematopoietic thymus         Cardiovascular heart         Nervous brain         Reproductive male system prostate       Visual eye uvea

tissue

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

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

three dsRNA-binding domains (dsRBDs), the first and second dsRBDs (dsRBD1 and dsRBD2, respectively) have affinities for dsRNA, whereas the third dsRBD (dsRBD3) binds to DICER1

mono polymer

heteromer , trimer

HOMOLOGY

interspecies	ortholog to Tarbp2, murine
	ortholog to Tarbp2, Rattus norvegicus
	ortholog to tarbp2, Danio rerio
	homolog to LOC736926, Pan troglodytes

Homologene

FAMILY

CATEGORY

RNA associated

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus

basic FUNCTION	activating HIV-1 gene expression in synergy with the viral Tat protein
	TARBP2 enhanced expression of the HIV-1 LTR in human
	and murine cells
	facilitating the production of small interfering RNA (siRNA) by Dicer
	TRBP, inhibits the activity of the interferon-induced protein kinase R (PKR)
	during development, TRBP has a function in spermatogenesis and growth control
	TRBP regulates the activation of PKR by controlling its accessibility to the PKR activator (PRKRA)
	double-stranded RNA (dsRNA)-binding protein, which binds to DiCER1 and is required for the RNA interference pathway
	TRBP has an oncogenic potential due to its interaction with PKR and the tumor suppressor Merlin induces its degradation by ubiquitination
	its activities at the molecular level impact the cellular function from normal development to cancer and the response to infections
	double-stranded RNA-specific diffusion activity of TARBP2 contributes to enhancing siRNA and miRNA processing by DICER1
	cytoplasmic RISC proteins PRKRA, TARBP2, and DICER1 are steroid receptor RNA activator (SRA) binding nuclear receptor coregulators that target steroid-responsive promoters and regulate nuclear receptor activity and downstream gene expression
	non-canonical and direct role for TARBP2 in gene expression regulation and regulated RNA destabilization through protein-mediated binding of mRNA structural elements can govern cancer progression
	RNA-binding protein (RBP) involved in miRNA processing and maturation

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

PRKRA is associated with a ~500 kDa complex that contains DICER1, AGO2, and TARBP2 and it associates with DICER1 to facilitate the production of small interfering RNA

INTERACTION

DNA

RNA

small molecule

protein	interaction with NF2 (merlin-binding protein)
	TRBP2 binds to HIV-1 TAR RNA and synergizes with HIV-1 Tat to activate the HIV-1 LTR promoter
	TRAF4
	protein kinase R (PKR)
	dicer-TRBP complex associates with Argonaute-2
	the tumor suppressor Merlin
	interacts directly with the DICER1 protein and is required for the stabilization of the DICER1 protein (Melo 2009)
	AGO2, PRKRA and TARBP2 were required for the efficient functioning of DICER1 in cells, and likely one of the roles of these proteins is to assure better synchronization of cleavages triggered by two RNase III domains of DICER1
	PRKRA and TARBP2 have distinct effects on DICER1-mediated dsRNA processing
	interface residues conserved between TARBP2 and PRKRA show that the proteins bind to DICER1 in a similar manner and by mutual exclusion
	FTSJ3 is a 2'O-MTase that is recruited to HIV RNA through TARBP2

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral   LOH     in mesothelioma tumoral     --over   in endometrial cancer metastasis tumoral somatic mutation     loss of function truncating mutations in tumors with microsatellite instability causing diminished TRBP protein expression and defective processing of miRNAs (Melo 2009) tumoral     --over   in many cancers such as prostate cancer, cutaneous malignant melanoma, and adrenocortical carcinoma tumoral     --low   in some cancers including colorectal cancer, gastric cancer, Ewing sarcoma, and upper urinary tract urothelial carcinoma

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	breast cancer patients with TARBP2 cytoplasm expression have unfavorable prognosis, and patients of triple-negative breast cancer (TNBC) and late-stage breast cancer with higher cytoplasm TARBP2 expression have an unfavorable prognosis
Therapy target

ANIMAL & CELL MODELS

mice homozygous for the mutant Prkra allele had defects not only in ear development but also growth, craniofacial development and ovarian structure