TARBP2

Summary

TARBP2 (TARBP2 subunit of RISC loading complex, HGNC:11569) is a protein-coding gene on chromosome 12q13.13, encoding RISC-loading complex subunit TARBP2 (Q15633). Required for formation of the RNA induced silencing complex (RISC).

HIV-1, the causative agent of acquired immunodeficiency syndrome (AIDS), contains an RNA genome that produces a chromosomally integrated DNA during the replicative cycle. Activation of HIV-1 gene expression by the transactivator Tat is dependent on an RNA regulatory element (TAR) located downstream of the transcription initiation site. The protein encoded by this gene binds between the bulge and the loop of the HIV-1 TAR RNA regulatory element and activates HIV-1 gene expression in synergy with the viral Tat protein. Alternative splicing results in multiple transcript variants encoding different isoforms. This gene also has a pseudogene.

Source: NCBI Gene 6895 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 51 total
• Druggable target: yes — 2 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_134323

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:11569
Approved symbol	TARBP2
Name	TARBP2 subunit of RISC loading complex
Location	12q13.13
Locus type	gene with protein product
Status	Approved
Aliases	Trbp
Ensembl gene	ENSG00000139546
Ensembl biotype	protein_coding
OMIM	605053
Entrez	6895

Gene structure

Transcript identifiers

Ensembl transcripts: 21 — 8 protein_coding, 7 retained_intron, 5 nonsense_mediated_decay, 1 protein_coding_CDS_not_defined

ENST00000266987, ENST00000394357, ENST00000456234, ENST00000546763, ENST00000546889, ENST00000547064, ENST00000547388, ENST00000547541, ENST00000548971, ENST00000549028, ENST00000549572, ENST00000549610, ENST00000549679, ENST00000550147, ENST00000550407, ENST00000551157, ENST00000551741, ENST00000552650, ENST00000552817, ENST00000552857, ENST00000710362

RefSeq mRNA: 3 — MANE Select: NM_134323 NM_004178, NM_134323, NM_134324

CCDS: CCDS41791, CCDS8861

Canonical transcript exons

ENST00000266987 — 9 exons

Exon	Start	End
ENSE00002344790	53501283	53501461
ENSE00003484119	53504397	53504469
ENSE00003503549	53505135	53505262
ENSE00003517867	53505649	53505850
ENSE00003531004	53505991	53506431
ENSE00003537599	53503027	53503129
ENSE00003539767	53504698	53504815
ENSE00003598683	53502015	53502184
ENSE00003647750	53503713	53503808

Expression profiles

Bgee: expression breadth ubiquitous, 213 present calls, max score 96.81.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 16.9617 / max 104.0521, expressed in 1787 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
125793	13.4466	1771
125794	2.6443	1102
125792	0.8708	460

Top tissues by expression

277 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	96.81	gold quality
cerebellar hemisphere	UBERON:0002245	96.56	gold quality
cerebellar cortex	UBERON:0002129	96.42	gold quality
cerebellum	UBERON:0002037	94.15	gold quality
right uterine tube	UBERON:0001302	93.50	gold quality
metanephros cortex	UBERON:0010533	92.84	gold quality
right lobe of thyroid gland	UBERON:0001119	92.15	gold quality
right adrenal gland	UBERON:0001233	92.08	gold quality
right adrenal gland cortex	UBERON:0035827	91.56	gold quality
mucosa of transverse colon	UBERON:0004991	91.20	gold quality
granulocyte	CL:0000094	90.98	gold quality
left lobe of thyroid gland	UBERON:0001120	90.94	gold quality
right lobe of liver	UBERON:0001114	90.83	gold quality
body of pancreas	UBERON:0001150	90.79	gold quality
left adrenal gland	UBERON:0001234	90.53	gold quality
stromal cell of endometrium	CL:0002255	90.40	gold quality
left adrenal gland cortex	UBERON:0035825	90.36	gold quality
endometrium epithelium	UBERON:0004811	90.31	gold quality
right testis	UBERON:0004534	89.79	gold quality
apex of heart	UBERON:0002098	89.62	gold quality
body of stomach	UBERON:0001161	89.56	gold quality
thyroid gland	UBERON:0002046	89.45	gold quality
spleen	UBERON:0002106	89.28	gold quality
minor salivary gland	UBERON:0001830	89.22	gold quality
body of uterus	UBERON:0009853	88.94	gold quality
endocervix	UBERON:0000458	88.86	gold quality
left testis	UBERON:0004533	88.75	gold quality
adrenal cortex	UBERON:0001235	88.62	gold quality
lower esophagus mucosa	UBERON:0035834	88.62	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	88.52	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.20

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): SP1, TFAP2A, TFAP4

miRNA regulators (miRDB)

16 targeting TARBP2, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-103A-3P	99.98	69.14	1595
HSA-MIR-107	99.98	69.14	1595
HSA-MIR-497-5P	99.92	71.83	2674
HSA-MIR-15A-5P	99.90	72.80	2787
HSA-MIR-15B-5P	99.90	72.78	2798
HSA-MIR-16-5P	99.90	72.80	2780
HSA-MIR-195-5P	99.90	72.81	2805
HSA-MIR-424-5P	99.89	71.90	2641
HSA-MIR-6838-5P	99.89	71.94	2690
HSA-MIR-1827	99.63	68.57	3265
HSA-MIR-6847-5P	97.93	66.74	1808
HSA-MIR-4257	97.86	68.05	1190
HSA-MIR-6787-3P	97.75	66.17	1233
HSA-MIR-2467-5P	97.36	67.71	991
HSA-MIR-597-5P	96.82	67.57	732

Literature-anchored findings (GeneRIF, showing 40)

• binds to merlin, which inhibits its oncogenic activity; results provide the first clue to the functional interaction between TRBP and merlin and suggest a novel mechanism for the tumor suppressor function of merlin both in vitro and in vivo (PMID:15123692)
• Data suggest that the cell specifity of HIV-1 expression and replication may be regulated, in part, through the control of TRBP1 expression by NF-Y factors. (PMID:16343534)
• These results suggest that, in the context of HIV replication, TRBP contributes mainly to the enhancement of virus production and that Dicer does not mediate HIV restriction by RNAi. (PMID:17360756)
• Results indicate that human TRBP and PACT directly interact with each other and associate with Dicer to stimulate the cleavage of double-stranded or short hairpin RNA to siRNA. (PMID:17452327)
• Ago2, Dicer, and TRBP comprise the RISC-loading complex (RLC) and assembles spontaneously in vitro from purified components (PMID:18178619)
• TRBP controls PACT activation of PKR, an activity that is reversed by stress. (PMID:18936160)
• RDE-4 preferentially binds long dsRNA, while TRBP binds siRNA with an affinity that is independent of dsRNA length. (PMID:18948111)
• Binding of Dicer to TRBPs is critical for RNAi function. (PMID:19422693)
• The RLC Dicer’s N-terminal DExH/D domain, located in a short ‘base branch’, interacts with TRBP, whereas its C-terminal catalytic domains in the main body are proximal to AGO2. (PMID:19820710)
• the three-dimensional structure of human Dicer bound to the protein TRBP at approximately 20 A resolution determined by negative-stain electron microscopy (EM) and single-particle analysis (PMID:19836333)
• TARBP2 frameshift mutation is associated with hereditary nonpolyposis colorectal cancer. (PMID:20877318)
• The structures dsRNA-bdinding domain 1 and dsRNA binding domain 2 solved by x-ray crystallography and NMR spectroscopy respectively. (PMID:21080422)
• results demonstrate for the first time that stress-induced PACT phosphorylation functions to free PACT from the inhibitory interaction with TRBP and also to enhance its interaction with PKR (PMID:21526770)
• There was no significant difference in the TARBP2 expression levels between the epithelial skin cancer groups and the healthy controls (P > 0.05). (PMID:22025453)
• AGO2, PACT and TRBP are required for the efficient functioning of Dicer in cells (PMID:22163034)
• Data suggest that cancer stem cell (CSC) self-renewal and tumor maintenance may depend on deregulation of TARBP2-dependent miRNA expression. (PMID:22698405)
• The studies in this review show that TRBP is multifunctional and mediates cross talk between different pathways. Its activities at the molecular level impact the cellular function from normal development to cancer and the response to infections. (PMID:22933564)
• Depletion of Dicer and TRBP, proteins involved in miRNA biogenesis, reduced HCV RNA accumulation, mature duplex miR-122 abundance, and miR-122 directed mRNA translation suppression, suggesting roles in miR-122 processing. (PMID:22999255)
• TRBP is a key regulator of miRNA processing and targeting in humans. (PMID:23006623)
• We report an unanticipated dsRNA diffusion behavior of TRBP, which requires two double-stranded RNA binding domains, and its correlation with the role of TRBP in promoting Dicer-induced RNA cleavage. (PMID:23251028)
• Results show that the region of TRBP that binds immature miRNAs comprises two independent double-stranded RNA-binding domains connected by a 60-residue flexible linker. (PMID:23435228)
• RISC proteins PACT, TRBP, and Dicer, together with PKR, are steroid receptor RNA activator-binding nuclear receptor coregulators that are recruited to the promoters of hormone-regulated genes and regulate the expression of downstream target genes. (PMID:23550157)
• in vitro binding patterns of human TRBP and PACT to siRNA (PMID:23658827)
• The results show that PACT and TRBP have distinct effects on Dicer-mediated dsRNA processing. (PMID:23661684)
• mRNA expression of TARBP2, but not DICER or DROSHA, is a strong molecular predictor to discriminate between adrenocortical adenomas and carcinomas (PMID:23671264)
• No frameshift mutations in TARBP2 were identified in a study of 4 cases of upper urinary tract urothelial carcinoma with high microsatellite instability status. (PMID:23690119)
• RPL5 binds to the TRBP2 and Ago2 subunits of the RISC and mediates the binding to c-Myc 3’UTR. (PMID:24141778)
• TARBP2 expression is upregulated in late-stage breast cancer and triple-negative breast cancer and may have a role in poorer disease-free survival and overall survival (PMID:24563327)
• Tarbp2 binding to TRPC4 promotes changes of cytosolic Ca(2+) and, thereby, leads to a dynamic regulation of Dicer activity, essentially at low endogenous Dicer concentrations. (PMID:24563462)
• identified TARBP2, a double-stranded RNA-binding protein implicated in microRNA processing, as the trans factor that binds the sRSE family and similar structural elements–collectively termed TARBP2-binding structural elements (TBSEs)–in transcripts (PMID:25043050)
• the role of TRBP and unveils negative feedback regulation of PKR through TRBP phosphorylation. (PMID:25437560)
• Results show the crystal structure of the interface between microRNA biogenesis proteins Dicer and TRBP. Mutations in this interface prevent recruitment of TRBP to Dicer. (PMID:25557550)
• HIV-1 Rev-response element RNA acts as an RNA silencing suppressor by competing with TRBP-bound siRNAs. (PMID:25668122)
• TARBP2 has roles in tumor development and progression [review] (PMID:26486325)
• SUMOylation of TARBP2 is required for regulating siRNA efficiency. (PMID:26582366)
• A statistically significant association with the risk of AD was observed with the CT genotype for rs784567 on the TARBP2 gene. on controlling for age and sex, we found that for the TARBP2-RNASEN association with AD the age variation was a risk factor for AD risk (P<0.001; OR=1.104; 95% CI, 1.059-1.151). (PMID:26796812)
• Experimental and computational techniques were employed to examine the hypothesis that TRBP-double-stranded RNA-binding domain (dsRBD) 2 binding by a 20-mer dsRNA is coupled with RNA bending, results suggest that this particular dsRBD-dsRNA interaction produces little to no change in the A-form geometry of dsRNA in solution (PMID:27332119)
• We propose that the S6K2/TRBP node controls miRNA biogenesis in HDLECs and provides a molecular link between the mTOR pathway and the miRNA biogenesis machinery. (PMID:27407113)
• TARBP2 silencing inhibits in vitro invasion and migration of NCIH1299 nonsmall cell lung cancer cell via the JNK/STAT3/AKT pathway. TARBP2 silencing does not significantly affect cell growth. (PMID:27599909)
• TRBP is required for normal antiviral responses to Cardiovirus infection. (PMID:27743889)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	tarbp2	ENSDARG00000070471
mus_musculus	Tarbp2	ENSMUSG00000023051
rattus_norvegicus	Tarbp2	ENSRNOG00000042355
drosophila_melanogaster	loqs	FBGN0032515
drosophila_melanogaster	CG12493	FBGN0035571
drosophila_melanogaster	blanks	FBGN0035608
drosophila_melanogaster	Zn72D	FBGN0263603
caenorhabditis_elegans	zfr-1	WBGENE00022388

Paralogs (14): STAU2 (ENSG00000040341), ZFR (ENSG00000056097), ADAT1 (ENSG00000065457), ZFR2 (ENSG00000105278), STAU1 (ENSG00000124214), ILF3 (ENSG00000129351), ADAD2 (ENSG00000140955), ILF2 (ENSG00000143621), ADAR (ENSG00000160710), ADAD1 (ENSG00000164113), STRBP (ENSG00000165209), PRKRA (ENSG00000180228), ADARB2 (ENSG00000185736), ADARB1 (ENSG00000197381)

Protein

Protein identifiers

RISC-loading complex subunit TARBP2 — Q15633 (reviewed: Q15633)

Alternative names: TAR RNA-binding protein 2, Trans-activation-responsive RNA-binding protein

All UniProt accessions (11): Q15633, A0AA34QVS4, F8VP94, F8VSA1, F8VTT7, F8VW32, F8VYK3, F8VYK6, F8VZ57, F8VZZ7, H3BV98

UniProt curated annotations — full annotation on UniProt →

Function. Required for formation of the RNA induced silencing complex (RISC). Component of the RISC loading complex (RLC), also known as the micro-RNA (miRNA) loading complex (miRLC), which is composed of DICER1, AGO2 and TARBP2. Within the RLC/miRLC, DICER1 and TARBP2 are required to process precursor miRNAs (pre-miRNAs) to mature miRNAs and then load them onto AGO2. AGO2 bound to the mature miRNA constitutes the minimal RISC and may subsequently dissociate from DICER1 and TARBP2. May also play a role in the production of short interfering RNAs (siRNAs) from double-stranded RNA (dsRNA) by DICER1. Binds in vitro to the PRM1 3’-UTR. Seems to act as a repressor of translation. For some pre-miRNA substrates, may also alter the choice of cleavage site by DICER1. Negatively regulates IRF7-mediated IFN-beta signaling triggered by viral infection by inhibiting the phosphorylation of IRF7 and promoting its ‘Lys’-48-linked ubiquitination and degradation. (Microbial infection) Binds to the HIV-1 TAR RNA which is located in the long terminal repeat (LTR) of HIV-1, and stimulates translation of TAR-containing RNAs. This is achieved in part at least by binding to and inhibiting EIF2AK2/PKR, thereby reducing phosphorylation and inhibition of EIF2S1/eIF-2-alpha. May also promote translation of TAR-containing RNAs independently of EIF2AK2/PKR. Mediates recruitment of FTSJ3 methyltransferase to HIV-1 RNA, leading to 2’-O-methylation of the viral genome, allowing HIV-1 to escape the innate immune system.

Subunit / interactions. Self-associates. Component of the RISC loading complex (RLC), or micro-RNA (miRNA) loading complex (miRLC), which is composed of DICER1, AGO2 and TARBP2. Note that the trimeric RLC/miRLC is also referred to as RISC. Interacts with EIF2AK2/PKR and inhibits its protein kinase activity. Interacts with DHX9 and PRKRA. Interacts with DICER1, AGO2, MOV10, EIF6 and RPL7A (60S ribosome subunit); they form a large RNA-induced silencing complex (RISC). Interacts with IRF7; this interaction prevents IRF7 phosphorylation and activation. (Microbial infection) Interacts with FTSJ3; forms a complex with FTSJ3 and HIV-1 TAR RNA. (Microbial infection) Interacts with ebolavirus VP30; this interaction, which occurs only in the presence of siRNA, prevents TARBP2 binding to DICER1 and thus allows the virus to counteract host RNA silencing. (Microbial infection) Interacts with ebolavirus VP35; this interaction prevents TARBP2 binding to DICER1 and thus allows the virus to counteract host RNA silencing.

Subcellular location. Cytoplasm. Perinuclear region. Nucleus.

Similarity. Belongs to the TARBP2 family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15633-1	1, TRBP2	yes
Q15633-2	2, TRBP1

RefSeq proteins (3): NP_004169, NP_599150, NP_599151 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR014720	dsRBD_dom	Domain
IPR028605	TRBP2	Family
IPR044469	TRBP2_DSRM_1	Domain
IPR044470	TRBP2_DSRM_2	Domain
IPR044471	TRBP2_DSRM_3	Domain
IPR051247	RLC_Component	Family

Pfam: PF00035

UniProt features (35 total): strand 12, helix 11, region of interest 4, domain 3, chain 1, sequence variant 1, sequence conflict 1, modified residue 1, splice variant 1

Structure

Experimental structures (PDB)

10 structures.

PDB	Method	Resolution (Å)
6ZBK	X-RAY DIFFRACTION	1.49
3LLH	X-RAY DIFFRACTION	2.14
3ADL	X-RAY DIFFRACTION	2.2
4WYQ	X-RAY DIFFRACTION	3.2
5ZAK	ELECTRON MICROSCOPY	4.4
5ZAL	ELECTRON MICROSCOPY	4.7
5ZAM	ELECTRON MICROSCOPY	5.7
2CPN	SOLUTION NMR
5N8L	SOLUTION NMR
5N8M	SOLUTION NMR

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15633-F1	75.31	0.46

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (1): 152

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-203927	MicroRNA (miRNA) biogenesis
R-HSA-426486	Small interfering RNA (siRNA) biogenesis
R-HSA-9833482	PKR-mediated signaling

MSigDB gene sets: 271 (showing top): GOBP_SINGLE_FERTILIZATION, GOBP_SKELETAL_MUSCLE_TISSUE_REGENERATION, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_KINASE_ACTIVITY, REACTOME_CYTOKINE_SIGNALING_IN_IMMUNE_SYSTEM, GOBP_REGULATION_OF_DEFENSE_RESPONSE_TO_VIRUS, GOBP_POSITIVE_REGULATION_OF_MUSCLE_CELL_DIFFERENTIATION, MODULE_45, GOBP_GROWTH, GOBP_POSITIVE_REGULATION_OF_VIRAL_GENOME_REPLICATION, LINDGREN_BLADDER_CANCER_CLUSTER_3_DN, GOBP_REGENERATION, GOBP_REGULATION_OF_TRANSFERASE_ACTIVITY, GOBP_MALE_GAMETE_GENERATION, MODULE_16

GO Biological Process (28): negative regulation of protein kinase activity (GO:0006469), spermatid development (GO:0007286), single fertilization (GO:0007338), siRNA processing (GO:0030422), pre-miRNA processing (GO:0031054), miRNA processing (GO:0035196), multicellular organism growth (GO:0035264), negative regulation of cytoplasmic pattern recognition receptor signaling pathway (GO:0039532), skeletal muscle tissue regeneration (GO:0043403), positive regulation of viral genome replication (GO:0045070), positive regulation of translation (GO:0045727), regulation of viral transcription (GO:0046782), negative regulation of defense response to virus by host (GO:0050689), positive regulation of muscle cell differentiation (GO:0051149), neural precursor cell proliferation (GO:0061351), regulation of regulatory ncRNA processing (GO:0070920), regulation of siRNA processing (GO:0070921), RISC complex assembly (GO:0070922), global gene silencing by mRNA cleavage (GO:0098795), regulation of miRNA processing (GO:1903798), cytoplasmic pattern recognition receptor signaling pathway (GO:0002753), regulation of translation (GO:0006417), regulation of gene expression (GO:0010468), post-transcriptional regulation of gene expression (GO:0010608), regulatory ncRNA-mediated gene silencing (GO:0031047), regulation of protein metabolic process (GO:0051246), protein K63-linked ubiquitination (GO:0070534), regulation of primary metabolic process (GO:0080090)

GO Molecular Function (11): double-stranded RNA binding (GO:0003725), enzyme binding (GO:0019899), siRNA binding (GO:0035197), miRNA binding (GO:0035198), pre-mRNA binding (GO:0036002), identical protein binding (GO:0042802), protein homodimerization activity (GO:0042803), pre-miRNA binding (GO:0070883), protein sequestering activity (GO:0140311), RNA binding (GO:0003723), protein binding (GO:0005515)

GO Cellular Component (8): nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), RISC complex (GO:0016442), nuclear body (GO:0016604), perinuclear region of cytoplasm (GO:0048471), RISC-loading complex (GO:0070578)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Gene Silencing by RNA	2
Antimicrobial mechanism of IFN-stimulated genes	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
regulatory ncRNA processing	3
RNA binding	3
protein binding	3
miRNA processing	2
regulation of regulatory ncRNA processing	2
regulatory RNA binding	2
cytoplasm	2
negative regulation of protein phosphorylation	1
protein kinase activity	1
negative regulation of kinase activity	1
regulation of protein kinase activity	1
germ cell development	1
spermatid differentiation	1
fertilization	1
multicellular organismal process	1
developmental growth	1
negative regulation of immune system process	1
cytoplasmic pattern recognition receptor signaling pathway	1
regulation of cytoplasmic pattern recognition receptor signaling pathway	1
negative regulation of intracellular signal transduction	1
tissue regeneration	1
viral genome replication	1
regulation of viral genome replication	1
positive regulation of viral process	1
translation	1
regulation of translation	1
positive regulation of gene expression	1
positive regulation of protein metabolic process	1
viral transcription	1
regulation of viral process	1
negative regulation of defense response to virus	1
regulation of defense response to virus by host	1
muscle cell differentiation	1
positive regulation of cell differentiation	1
regulation of muscle cell differentiation	1
cell population proliferation	1
regulation of gene silencing by regulatory ncRNA	1
regulation of primary metabolic process	1
siRNA processing	1

Protein interactions and networks

STRING

1208 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
TARBP2	DICER1	Q9UPY3	999
TARBP2	AGO2	Q9UKV8	998
TARBP2	AGO1	Q9UL18	963
TARBP2	RBM8A	Q9Y5S9	956
TARBP2	DROSHA	Q9NRR4	939
TARBP2	TNRC6A	Q8NDV7	935
TARBP2	XPO5	Q9HAV4	886
TARBP2	DGCR8	Q8WYQ5	884
TARBP2	PRKRA	O75569	875
TARBP2	GEMIN4	P57678	805
TARBP2	HENMT1	Q5T8I9	787
TARBP2	PIWIL4	Q7Z3Z4	768
TARBP2	PIWIL1	Q96J94	757
TARBP2	AGO3	Q9H9G7	740
TARBP2	AGO4	Q9HCK5	740

IntAct

211 interactions, top by confidence:

A	B	Type	Score
DICER1	TARBP2	psi-mi:“MI:0915”(physical association)	0.960
TARBP2	DICER1	psi-mi:“MI:0915”(physical association)	0.960
AGO2	TARBP2	psi-mi:“MI:0915”(physical association)	0.930
AGO2	TARBP2	psi-mi:“MI:0914”(association)	0.930
TARBP2	PRKRA	psi-mi:“MI:0915”(physical association)	0.920
PRKRA	TARBP2	psi-mi:“MI:0915”(physical association)	0.920
DICER1	PRKRA	psi-mi:“MI:0914”(association)	0.800
DICER1	TARBP2	psi-mi:“MI:0915”(physical association)	0.780
DICER1	TARBP2	psi-mi:“MI:0407”(direct interaction)	0.780
TARBP2	TARBP2	psi-mi:“MI:0915”(physical association)	0.740
ZNF346	TARBP2	psi-mi:“MI:0915”(physical association)	0.720

BioGRID (199): TARBP2 (Two-hybrid), PRKRA (Two-hybrid), ZNF346 (Two-hybrid), STRBP (Two-hybrid), TCEANC (Two-hybrid), TARBP2 (Affinity Capture-RNA), TARBP2 (Affinity Capture-MS), TARBP2 (Affinity Capture-MS), TARBP2 (Affinity Capture-MS), TARBP2 (Affinity Capture-MS), TARBP2 (Affinity Capture-MS), TARBP2 (Affinity Capture-MS), TARBP2 (Affinity Capture-MS), TARBP2 (Affinity Capture-MS), TARBP2 (Affinity Capture-MS)

ESM2 similar proteins: A6NDL7, A6QLE1, B0K012, B0V3F8, D2H0H6, E1B8U2, O75569, O94955, P55265, P55266, P97473, P97616, Q0IIG6, Q15633, Q2HJ92, Q2TBA3, Q3LAC4, Q3SWU0, Q3U2J5, Q4L235, Q4SS66, Q4V8C7, Q587J7, Q5BJ52, Q5RAH6, Q5ZLS2, Q6GPZ1, Q6GQ33, Q6GR37, Q6P5G6, Q70Z35, Q7SXR1, Q7ZYA5, Q80VL1, Q8IWR0, Q8NA31, Q8NHU6, Q8TCU6, Q91836, Q922P9

Diamond homologs: A1AE97, A1JKK3, A3MZQ9, A4TKX8, A5F5H8, A6TCI1, A7FFT9, A7ZQ11, A8A377, A8F397, A8GI25, A8GM79, A8GYE2, A9R402, A9WJ69, B0BUA6, B0V3F8, B1IVR0, B1LP80, B1XB41, B2TXY0, B2VI46, B4F047, B5BAT0, B5QTU8, B5RD49, B5XNH0, B5Z141, B6I5E1, B7LDG0, B7LUZ7, B7M8I0, B7MIQ2, B7MYJ8, B7N6F5, B7NRM0, B7UH07, B8GAM6, B9KGT5, B9LB70

SIGNOR signaling

8 interactions.

A	Effect	B	Mechanism
TARBP2	up-regulates	DICER1	binding
TARBP2	“form complex”	RISC(DICER1/AGO2/TARBP2)	binding
AKT1	“up-regulates activity”	TARBP2	phosphorylation
RPS6KB1	“up-regulates activity”	TARBP2	phosphorylation
RPS6KB2	“up-regulates activity”	TARBP2	phosphorylation

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 145 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
MicroRNA (miRNA) biogenesis	6	28.9×	6e-06
PKR-mediated signaling	8	11.9×	2e-05
Nonsense Mediated Decay (NMD) independent of the Exon Junction Complex (EJC)	9	11.2×	1e-05
Peptide chain elongation	8	10.7×	4e-05
Viral mRNA Translation	8	10.7×	4e-05
PELO:HBS1L and ABCE1 dissociate a ribosome on a non-stop mRNA	8	10.6×	4e-05
SRP-dependent cotranslational protein targeting to membrane	10	10.5×	6e-06
Selenocysteine synthesis	8	10.1×	4e-05

GO biological processes:

GO term	Partners	Fold	FDR
pre-miRNA processing	7	60.5×	4e-09
miRNA processing	5	40.5×	2e-05
cytoplasmic translation	10	14.2×	6e-07
negative regulation of translation	7	10.6×	5e-04
translation	11	8.7×	1e-05

Disease & clinical

Clinical variants and AI predictions

ClinVar

51 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	37
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

1594 predictions. Top by Δscore:

Variant	Effect	Δscore
12:53502013:A:AG	acceptor_gain	1.0000
12:53502014:G:GG	acceptor_gain	1.0000
12:53502014:GTATA:G	acceptor_gain	1.0000
12:53502185:G:GA	donor_loss	1.0000
12:53502190:G:GT	donor_gain	1.0000
12:53503567:G:GT	donor_gain	1.0000
12:53504695:A:AG	acceptor_gain	1.0000
12:53504695:AAG:A	acceptor_gain	1.0000
12:53504696:A:G	acceptor_gain	1.0000
12:53504798:A:T	donor_gain	1.0000
12:53504811:GATTG:G	donor_gain	1.0000
12:53504812:A:G	donor_gain	1.0000
12:53504816:G:GG	donor_gain	1.0000
12:53505129:A:AG	acceptor_gain	1.0000
12:53505129:AT:A	acceptor_gain	1.0000
12:53505130:T:G	acceptor_gain	1.0000
12:53505132:CAGG:C	acceptor_loss	1.0000
12:53505132:CAGGG:C	acceptor_gain	1.0000
12:53505133:A:AG	acceptor_gain	1.0000
12:53505133:AG:A	acceptor_gain	1.0000
12:53505133:AGGGA:A	acceptor_gain	1.0000
12:53505134:G:A	acceptor_loss	1.0000
12:53505134:G:GT	acceptor_gain	1.0000
12:53505134:GG:G	acceptor_gain	1.0000
12:53505134:GGGA:G	acceptor_gain	1.0000
12:53505134:GGGAG:G	acceptor_gain	1.0000
12:53505258:CCATT:C	donor_gain	1.0000
12:53505259:CATT:C	donor_gain	1.0000
12:53505260:ATT:A	donor_gain	1.0000
12:53505261:TT:T	donor_gain	1.0000

AlphaMissense

2356 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:53502053:C:A	P31Q	1.000
12:53502056:T:A	I32N	1.000
12:53502056:T:C	I32T	1.000
12:53502056:T:G	I32S	1.000
12:53502058:A:C	S33R	1.000
12:53502060:C:A	S33R	1.000
12:53502060:C:G	S33R	1.000
12:53502062:T:C	L34P	1.000
12:53502065:T:A	L35Q	1.000
12:53502065:T:C	L35P	1.000
12:53502068:A:C	Q36P	1.000
12:53502076:G:T	G39W	1.000
12:53502077:G:A	G39E	1.000
12:53502098:C:A	P46H	1.000
12:53502098:C:G	P46R	1.000
12:53502103:T:A	Y48N	1.000
12:53502103:T:C	Y48H	1.000
12:53502103:T:G	Y48D	1.000
12:53502110:T:C	L50P	1.000
12:53502124:G:C	G55R	1.000
12:53502124:G:T	G55C	1.000
12:53502125:G:A	G55D	1.000
12:53502125:G:T	G55V	1.000
12:53502133:C:A	H58N	1.000
12:53502133:C:G	H58D	1.000
12:53502135:C:A	H58Q	1.000
12:53502135:C:G	H58Q	1.000
12:53502145:T:A	F62I	1.000
12:53502145:T:C	F62L	1.000
12:53502145:T:G	F62V	1.000

dbSNP variants (sampled 300 via entrez): RS1000102741 (12:53506644 G>A), RS1000310038 (12:53502657 C>A,G), RS1000863261 (12:53502001 GCCC>G), RS1001356107 (12:53499173 C>A,T), RS1001745048 (12:53503420 C>T), RS1001798798 (12:53502996 C>T), RS1002399057 (12:53504260 G>A), RS1002698781 (12:53501767 T>A), RS1002751169 (12:53501399 G>C), RS1003167135 (12:53500695 T>A,C), RS1003248678 (12:53500158 A>G), RS1005092602 (12:53506512 C>G), RS1005158525 (12:53499798 C>T), RS1006098354 (12:53505010 T>G), RS1006813347 (12:53500271 G>A,C)

Disease associations

OMIM: gene MIM:605053 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST005956_70	Waist-to-hip ratio adjusted for BMI	4.000000e-13
GCST005957_6	Waist-to-hip ratio adjusted for BMI (age <50)	6.000000e-06
GCST005958_9	Waist-to-hip ratio adjusted for BMI (age >50)	1.000000e-08
GCST005962_20	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	7.000000e-13

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL2098 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

2 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 28,500 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1164729	FEBUXOSTAT	4	3,499
CHEMBL826	ENOXACIN	4	25,001

PharmGKB: 1 entry (VIP=true, CPIC=false)

ChEMBL bioactivities

63 potent at pChembl≥5 of 71 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.37	EC50	0.43	nM	CHEMBL6146528
9.33	EC50	0.47	nM	CHEMBL6134302
9.18	EC50	0.66	nM	CHEMBL6144191
9.05	EC50	0.9	nM	CHEMBL6151827
9.04	EC50	0.92	nM	CHEMBL6149206
8.84	EC50	1.46	nM	CHEMBL6143674
8.79	EC50	1.61	nM	CHEMBL6146814
8.76	EC50	1.72	nM	CHEMBL6160469
8.75	EC50	1.76	nM	CHEMBL6133340
8.68	EC50	2.09	nM	CHEMBL3326615
8.61	EC50	2.48	nM	CHEMBL6166283
8.49	EC50	3.21	nM	CHEMBL6159889
8.49	EC50	3.25	nM	CHEMBL6146376
8.43	EC50	3.75	nM	CHEMBL6143932
8.41	Kd	3.9	nM	CHEMBL6146528
8.38	EC50	4.14	nM	CHEMBL6145776
8.37	EC50	4.26	nM	CHEMBL6102924
8.32	Kd	4.78	nM	CHEMBL6144191
8.08	Kd	8.25	nM	CHEMBL6143626
8.01	EC50	9.87	nM	CHEMBL6143626
7.98	Kd	10.42	nM	CHEMBL5170759
7.93	Kd	11.67	nM	CHEMBL6146784
7.93	Kd	11.71	nM	CHEMBL6151827
7.84	EC50	14.51	nM	CHEMBL6146784
7.82	Kd	15.21	nM	CHEMBL5170759
7.72	Kd	19.19	nM	CHEMBL5180444
7.68	Kd	20.97	nM	CHEMBL6143674
7.56	EC50	27.32	nM	CHEMBL6143302
7.46	EC50	34.74	nM	CHEMBL6151180
7.45	EC50	35.62	nM	CHEMBL6133331
7.43	EC50	37.14	nM	CHEMBL6109004
7.39	EC50	41.15	nM	CHEMBL6152406
7.34	EC50	45.76	nM	CHEMBL6142408
7.23	EC50	59.21	nM	CHEMBL6146864
7.15	EC50	71.46	nM	CHEMBL6171457
7.14	EC50	71.58	nM	CHEMBL6103002
7.09	EC50	81.55	nM	CHEMBL6101979
7.08	EC50	83.8	nM	CHEMBL6145264
7.04	EC50	90.57	nM	FEBUXOSTAT
7.03	Kd	94	nM	ENOXACIN
6.90	Kd	126.1	nM	CHEMBL5178502
6.83	EC50	149.7	nM	CHEMBL6102571
6.81	EC50	154.5	nM	CHEMBL6161211
6.73	EC50	185.1	nM	CHEMBL6163281
6.63	Kd	235.4	nM	CHEMBL5175086
6.63	EC50	231.6	nM	CHEMBL6144454
6.50	EC50	318.8	nM	CHEMBL6144537
6.32	EC50	481.4	nM	CHEMBL6134423
6.19	EC50	640	nM	CHEMBL6142717
6.19	EC50	650	nM	CHEMBL6167757

PubChem BioAssay actives

11 with measured affinity, of 21 total; 10 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
ethyl 2-(4-methoxyphenyl)-5-methyl-1,3-oxazole-4-carboxylate	1884723: Binding affinity to human recombinant TRBP by SPR assay	kd	0.0104	uM
ethyl 5-methyl-2-(4-methylphenyl)-1,3-oxazole-4-carboxylate	1884723: Binding affinity to human recombinant TRBP by SPR assay	kd	0.0192	uM
1-ethyl-6-fluoro-4-oxo-7-piperazin-1-yl-1,8-naphthyridine-3-carboxylic acid	1692574: Enhancement of His6-tagged TRBP (unknown origin) expressed in Escherichia coli BL21(DE3) binding to 32P-labeled Let7 precursor RNA assessed as TRBP Kd at 30 uM incubated for 60 mins by liquid scintillation counting method (Rvb = 221 nM)	kd	0.0940	uM
ethyl 5-methyl-2-(4-phenylphenyl)-1,3-oxazole-4-carboxylate	1884723: Binding affinity to human recombinant TRBP by SPR assay	kd	0.1261	uM
ethyl 2-(4-bromophenyl)-5-methyl-1,3-oxazole-4-carboxylate	1884723: Binding affinity to human recombinant TRBP by SPR assay	kd	0.2354	uM
ethyl 5-ethyl-2-(4-methoxyphenyl)-1,3-oxazole-4-carboxylate	1884723: Binding affinity to human recombinant TRBP by SPR assay	kd	0.6798	uM
2-hydroxyethyl 5-methyl-2-(4-phenylphenyl)-1,3-oxazole-4-carboxylate	1884723: Binding affinity to human recombinant TRBP by SPR assay	kd	1.5020	uM
ethyl 2-(4-chlorophenyl)-5-methyl-1,3-oxazole-4-carboxylate	1884723: Binding affinity to human recombinant TRBP by SPR assay	kd	1.8220	uM
(9R,10S)-4,5,19-trimethoxy-9,10-dimethyl-15,17-dioxatetracyclo[10.7.0.02,7.014,18]nonadeca-1(19),2,4,6,12,14(18)-hexaen-3-ol	1884723: Binding affinity to human recombinant TRBP by SPR assay	kd	6.7900	uM
methyl 6-[4-[benzoyl(methyl)amino]phenyl]-7-methoxy-1,3-benzodioxole-5-carboxylate	1817266: Binding affinity to CM5 sensor chip immobilized recombinant full-length TRBP (unknown origin) assessed as dissociation constant by SPR analysis	kd	6.7900	uM

CTD chemical–gene interactions

30 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
bisphenol A	decreases expression, increases expression, affects cotreatment	2
FR900359	decreases phosphorylation	1
bisphenol F	decreases expression, affects cotreatment	1
methylselenic acid	decreases expression	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	increases abundance, increases expression	1
coumarin	increases phosphorylation	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	increases expression	1
bisphenol S	affects cotreatment, decreases expression	1
Air Pollutants	decreases expression, increases abundance	1
Arsenic	increases expression, increases abundance	1
Atrazine	decreases expression	1
Caffeine	affects phosphorylation	1
Cannabidiol	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Doxorubicin	decreases expression	1
Indomethacin	affects cotreatment, decreases expression	1
Ivermectin	decreases expression	1
Ribonucleotides	affects binding	1
Rotenone	decreases expression	1
Selenium	affects cotreatment, increases expression	1
Smoke	decreases expression	1
Thiram	decreases expression	1
Tobacco Smoke Pollution	decreases expression	1
Valproic Acid	affects expression	1
Vitamin E	affects cotreatment, increases expression	1
1-Methyl-3-isobutylxanthine	affects cotreatment, decreases expression	1
Aflatoxin B1	increases methylation	1
Particulate Matter	decreases expression, increases abundance	1

ChEMBL screening assays

23 unique, capped per target: 23 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL4687584	Binding	Enhancement of His6-tagged TRBP (unknown origin) expressed in Escherichia coli BL21(DE3) binding to 32P-labeled Let7 precursor RNA assessed as TRBP Kd at 30 uM incubated for 60 mins by liquid scintillation counting method (Rvb = 221 nM)	Modulating microRNA Processing: Enoxacin, the Progenitor of a New Class of Drugs. — J Med Chem

Cellosaurus cell lines

4 cell lines: 4 cancer cell line

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_TR60	HAP1 TARBP2 (-) 1	Cancer cell line	Male
CVCL_TR61	HAP1 TARBP2 (-) 2	Cancer cell line	Male
CVCL_TR62	HAP1 TARBP2 (-) 3	Cancer cell line	Male
CVCL_TR63	HAP1 TARBP2 (-) 4	Cancer cell line	Male

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.