Q15633 (TRBP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
RISC-loading complex subunit TARBP2

Alternative name(s):
TAR RNA-binding protein 2
Trans-activation-responsive RNA-binding protein

Gene names

Name:	TARBP2
Synonyms:	TRBP

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	366 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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, EIF2C2/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 EIF2C2/AGO2. EIF2C2/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 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. Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.20 Ref.22
Subunit structure	Self-associates. Component of the RISC loading complex (RLC), or micro-RNA (miRNA) loading complex (miRLC), which is composed of DICER1, EIF2C2/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, EIF6, MOV10 and PRKRA. Associates with the 60S ribosome. Ref.9 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.18 Ref.20 Ref.21
Subcellular location	Cytoplasm. Cytoplasm › perinuclear region. Nucleus Ref.15 Ref.16 Ref.21.
Sequence similarities	Belongs to the TARBP2 family. Contains 3 DRBM (double-stranded RNA-binding) domains.

Ontologies

Keywords
Biological process	RNA-mediated gene silencing Translation regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative promoter usage Polymorphism
Domain	Repeat
Ligand	RNA-binding
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	miRNA loading onto RISC involved in gene silencing by miRNA Inferred from direct assay Ref.14. Source: UniProtKB negative regulation of defense response to virus by host Inferred from direct assay Ref.7. Source: UniProtKB negative regulation of protein kinase activity Traceable author statement Ref.7. Source: UniProtKB positive regulation of viral genome replication Inferred from direct assay Ref.7. Source: UniProtKB pre-miRNA processing Inferred from direct assay Ref.14. Source: UniProtKB production of siRNA involved in RNA interference Inferred from direct assay Ref.14Ref.16. Source: UniProtKB regulation of transcription from RNA polymerase II promoter Traceable author statement Ref.1. Source: ProtInc regulation of translation Inferred from electronic annotation. Source: UniProtKB-KW regulation of viral transcription Inferred from direct assay Ref.7. Source: UniProtKB targeting of mRNA for destruction involved in RNA interference Inferred from mutant phenotype Ref.14. Source: UniProtKB
Cellular_component	RNA-induced silencing complex Inferred from direct assay Ref.14. Source: UniProtKB cytosol Traceable author statement. Source: Reactome nucleus Inferred from direct assay. Source: HPA perinuclear region of cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	double-stranded RNA binding Inferred from electronic annotation. Source: InterPro siRNA binding Inferred from direct assay Ref.14. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DICER1	Q9UPY3	8	EBI-978581,EBI-395506
EIF2AK2	P19525	2	EBI-978581,EBI-640775

Alternative products

This entry describes 2 isoforms produced by alternative promoter usage. [Align] [Select]

Isoform 1 (identifier: Q15633-1)

Also known as: TRBP2;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q15633-2)

Also known as: TRBP1;

The sequence of this isoform differs from the canonical sequence as follows:
     1-21: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 366

366

RISC-loading complex subunit TARBP2 HAMAP-Rule MF_03034

PRO_0000065622

Regions

Domain

30 – 97

68

DRBM 1

Domain

159 – 227

69

DRBM 2

Domain

293 – 361

69

DRBM 3

Region

22 – 105

84

Sufficient for interaction with PRKRA HAMAP-Rule MF_03034

Region

152 – 234

83

Sufficient for interaction with PRKRA HAMAP-Rule MF_03034

Region

228 – 366

139

Sufficient for interaction with DICER1 HAMAP-Rule MF_03034

Region

287 – 366

80

Sufficient for interaction with PRKRA HAMAP-Rule MF_03034

Natural variations

Alternative sequence

1 – 21

21

Missing in isoform 2.

VSP_035584

Natural variant

251

1

S → F. Ref.1 Ref.3
Corresponds to variant rs1126500 [ dbSNP | Ensembl ].

VAR_046992

Experimental info

Sequence conflict

144

1

P → A in AAA36765. Ref.1

Secondary structure

1

.

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.

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366

Helix Strand Turn

Details...

Helix

31 – 41

11

Beta strand

47 – 53

7

Beta strand

62 – 68

7

Beta strand

71 – 79

9

Helix

80 – 95

16

Helix

161 – 170

10

Beta strand

177 – 185

9

Beta strand

187 – 189

3

Beta strand

191 – 198

8

Beta strand

201 – 209

9

Helix

210 – 226

17

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (TRBP2) [UniParc]. Last modified October 14, 2008. Version 3. Checksum: 768BA11751DA4912	FASTA	366	39,039
	10 20 30 40 50 60 MSEEEQGSGT TTGCGLPSIE QMLAANPGKT PISLLQEYGT RIGKTPVYDL LKAEGQAHQP 70 80 90 100 110 120 NFTFRVTVGD TSCTGQGPSK KAAKHKAAEV ALKHLKGGSM LEPALEDSSS FSPLDSSLPE 130 140 150 160 170 180 DIPVFTAAAA ATPVPSVVLT RSPPMELQPP VSPQQSECNP VGALQELVVQ KGWRLPEYTV 190 200 210 220 230 240 TQESGPAHRK EFTMTCRVER FIEIGSGTSK KLAKRNAAAK MLLRVHTVPL DARDGNEVEP 250 260 270 280 290 300 DDDHFSIGVG SRLDGLRNRG PGCTWDSLRN SVGEKILSLR SCSLGSLGAL GPACCRVLSE 310 320 330 340 350 360 LSEEQAFHVS YLDIEELSLS GLCQCLVELS TQPATVCHGS ATTREAARGE AARRALQYLK IMAGSK
	Isoform 2 (TRBP1) [UniParc]. Checksum: 7506A9324E9D0596	FASTA	345	36,916
	10 20 30 40 50 60 MLAANPGKTP ISLLQEYGTR IGKTPVYDLL KAEGQAHQPN FTFRVTVGDT SCTGQGPSKK 70 80 90 100 110 120 AAKHKAAEVA LKHLKGGSML EPALEDSSSF SPLDSSLPED IPVFTAAAAA TPVPSVVLTR 130 140 150 160 170 180 SPPMELQPPV SPQQSECNPV GALQELVVQK GWRLPEYTVT QESGPAHRKE FTMTCRVERF 190 200 210 220 230 240 IEIGSGTSKK LAKRNAAAKM LLRVHTVPLD ARDGNEVEPD DDHFSIGVGS RLDGLRNRGP 250 260 270 280 290 300 GCTWDSLRNS VGEKILSLRS CSLGSLGALG PACCRVLSEL SEEQAFHVSY LDIEELSLSG 310 320 330 340 LCQCLVELST QPATVCHGSA TTREAARGEA ARRALQYLKI MAGSK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Characterization of a human TAR RNA-binding protein that activates the HIV-1 LTR." Gatignol A., Buckler-White A.J., Berkhout B., Jeang K.T. Science 251:1597-1600(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), VARIANT PHE-251.
[2]	Gatignol A., Duarte M. Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"Genetic mapping in human and mouse of the locus encoding TRBP, a protein that binds the TAR region of the human immunodeficiency virus (HIV-1)." Kozak C.A., Gatignol A., Graham K., Jeang K.T., McBride O.W. Genomics 25:66-72(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT PHE-251.
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Muscle.
[7]	"Organization of the human tarbp2 gene reveals two promoters that are repressed in an astrocytic cell line." Bannwarth S., Talakoub L., Letourneur F., Duarte M., Purcell D.F., Hiscott J., Gatignol A. J. Biol. Chem. 276:48803-48813(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-74, ALTERNATIVE PROMOTER USAGE.
[8]	"Relatedness of an RNA-binding motif in human immunodeficiency virus type 1 TAR RNA-binding protein TRBP to human P1/dsI kinase and Drosophila staufen." Gatignol A., Buckler C., Jeang K.T. Mol. Cell. Biol. 13:2193-2202(1993) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF RNA-BINDING.
[9]	"Two dimerization domains in the trans-activation response RNA-binding protein (TRBP) individually reverse the protein kinase R inhibition of HIV-1 long terminal repeat expression." Daher A., Longuet M., Dorin D., Bois F., Segeral E., Bannwarth S., Battisti P.-L., Purcell D.F., Benarous R., Vaquero C., Meurs E.F., Gatignol A. J. Biol. Chem. 276:33899-33905(2001) [PubMed] [Europe PMC] [Abstract] Cited for: SELF-ASSOCIATION, INTERACTION WITH EIF2AK2.
[10]	"The TAR RNA-binding protein, TRBP, stimulates the expression of TAR-containing RNAs in vitro and in vivo independently of its ability to inhibit the dsRNA-dependent kinase PKR." Dorin D., Bonnet M.C., Bannwarth S., Gatignol A., Meurs E.F., Vaquero C. J. Biol. Chem. 278:4440-4448(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[11]	"Human RISC couples microRNA biogenesis and posttranscriptional gene silencing." Gregory R.I., Chendrimada T.P., Cooch N., Shiekhattar R. Cell 123:631-640(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH DICER1 AND EIF2C2.
[12]	"TRBP, a regulator of cellular PKR and HIV-1 virus expression, interacts with Dicer and functions in RNA silencing." Haase A.D., Jaskiewicz L., Zhang H., Laine S., Sack R., Gatignol A., Filipowicz W. EMBO Rep. 6:961-967(2005) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, SELF-ASSOCIATION, INTERACTION WITH DICER1.
[13]	"A human, ATP-independent, RISC assembly machine fueled by pre-miRNA." Maniataki E., Mourelatos Z. Genes Dev. 19:2979-2990(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH DICER1 AND EIF2C2.
[14]	"TRBP recruits the Dicer complex to Ago2 for microRNA processing and gene silencing." Chendrimada T.P., Gregory R.I., Kumaraswamy E., Norman J., Cooch N., Nishikura K., Shiekhattar R. Nature 436:740-744(2005) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH DICER1 AND EIF2C2, RNA-BINDING.
[15]	"The role of PACT in the RNA silencing pathway." Lee Y., Hur I., Park S.-Y., Kim Y.-K., Suh M.R., Kim V.N. EMBO J. 25:522-532(2006) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, INTERACTION WITH DICER1; EIF2C2 AND PRKRA, SUBCELLULAR LOCATION.
[16]	"Human TRBP and PACT directly interact with each other and associate with dicer to facilitate the production of small interfering RNA." Kok K.H., Ng M.-H., Ching Y.-P., Jin D.-Y. J. Biol. Chem. 282:17649-17657(2007) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SELF-ASSOCIATION, INTERACTION WITH DICER1 AND PRKRA, SUBCELLULAR LOCATION.
[17]	"RNA helicase A interacts with RISC in human cells and functions in RISC loading." Robb G.B., Rana T.M. Mol. Cell 26:523-537(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DHX9.
[18]	"MicroRNA silencing through RISC recruitment of eIF6." Chendrimada T.P., Finn K.J., Ji X., Baillat D., Gregory R.I., Liebhaber S.A., Pasquinelli A.E., Shiekhattar R. Nature 447:823-828(2007) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH DICER1; EIF2C2; EIF6 AND MOV10, ASSOCIATION WITH THE 60S RIBOSOME.
[19]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[20]	"In vitro reconstitution of the human RISC-loading complex." MacRae I.J., Ma E., Zhou M., Robinson C.V., Doudna J.A. Proc. Natl. Acad. Sci. U.S.A. 105:512-517(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY, FUNCTION, INTERACTION WITH DICER1 AND EIF2C2.
[21]	"Interactions between the double-stranded RNA-binding proteins TRBP and PACT define the Medipal domain that mediates protein-protein interactions." Laraki G., Clerzius G., Daher A., Melendez-Pena C., Daniels S., Gatignol A. RNA Biol. 5:92-103(2008) [PubMed] [Europe PMC] [Abstract] Cited for: SELF-ASSOCIATION, INTERACTION WITH EIF2AK2 AND PRKRA, SUBCELLULAR LOCATION.
[22]	"A TARBP2 mutation in human cancer impairs microRNA processing and DICER1 function." Melo S.A., Ropero S., Moutinho C., Aaltonen L.A., Yamamoto H., Calin G.A., Rossi S., Fernandez A.F., Carneiro F., Oliveira C., Ferreira B., Liu C.-G., Villanueva A., Capella G., Schwartz S. Jr., Shiekhattar R., Esteller M. Nat. Genet. 41:365-370(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[23]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[24]	"Solution structure of the second DSRBD of TAR RNA-binding protein 2." RIKEN structural genomics initiative (RSGI) Submitted (NOV-2005) to the PDB data bank Cited for: STRUCTURE BY NMR OF 150-225.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M60801 mRNA. Translation: AAA36765.1.
U08998 mRNA. Translation: AAB50581.2.
BT007140 mRNA. Translation: AAP35804.1.
CH471054 Genomic DNA. Translation: EAW96720.1.
BC005860 mRNA. Translation: AAH05860.1.
AF281068 Genomic DNA. Translation: AAL55730.1.
AF281068 Genomic DNA. Translation: AAL55731.1.

IPI

IPI00472583.
IPI00847568.

PIR

G01420.

RefSeq

NP_004169.3. NM_004178.4.
NP_599150.1. NM_134323.1.
NP_599151.2. NM_134324.2.

UniGene

Hs.326.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2CPN	NMR	-	A	150-225	[»]
3ADL	X-ray	2.20	A	161-231	[»]
3LLH	X-ray	2.14	A/B	22-105	[»]

ProteinModelPortal

Q15633.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29665N.

IntAct

Q15633. 8 interactions.

MINT

MINT-92451.

STRING

9606.ENSP00000266987.

PTM databases

PhosphoSite

Q15633.

Polymorphism databases

DMDM

209572714.

Proteomic databases

PaxDb

Q15633.

PRIDE

Q15633.

Protocols and materials databases

DNASU

6895.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000266987; ENSP00000266987; ENSG00000139546.
ENST00000394357; ENSP00000377885; ENSG00000139546.
ENST00000456234; ENSP00000416077; ENSG00000139546.

GeneID

6895.

KEGG

hsa:6895.

UCSC

uc001sdo.3. human.

Organism-specific databases

CTD

6895.

GeneCards

GC12P053890.

HGNC

HGNC:11569. TARBP2.

HPA

HPA051181.

MIM

605053. gene.

neXtProt

NX_Q15633.

PharmGKB

PA36334.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG245126.

HOGENOM

HOG000231919.

HOVERGEN

HBG001700.

InParanoid

Q15633.

OMA

CRVERFV.

OrthoDB

EOG48GW3W.

PhylomeDB

Q15633.

Enzyme and pathway databases

Reactome

REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

Q15633.

Bgee

Q15633.

CleanEx

HS_TARBP2.

Genevestigator

Q15633.

GermOnline

ENSG00000139546. Homo sapiens.

Family and domain databases

Gene3D

3.30.160.20. 3 hits.

HAMAP

MF_03034. TRBP2.

InterPro

IPR001159. Ds-RNA-bd.
IPR014720. dsRNA-bd-like_dom.
[Graphical view]

Pfam

PF00035. dsrm. 2 hits.
[Graphical view]

SMART

SM00358. DSRM. 3 hits.
[Graphical view]

PROSITE

PS50137. DS_RBD. 3 hits.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q15633.

ChEMBL

CHEMBL2098.

EvolutionaryTrace

Q15633.

GenomeRNAi

6895.

NextBio

26949.

SOURCE

Search...

Entry information

Entry name

TRBP2_HUMAN

Accession

Primary (citable) accession number: Q15633
Secondary accession number(s): Q12878 , Q8WY32, Q8WY33, Q9BRY2

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	October 14, 2008
Last modified:	May 1, 2013
This is version 122 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.