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Q15633 (TRBP2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length366 AA.
Sequence statusComplete.
Protein existenceEvidence 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, 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 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, 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. Cytoplasmperinuclear 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 processRNA-mediated gene silencing
Translation regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative promoter usage
Polymorphism
   DomainRepeat
   LigandRNA-binding
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processgene expression

Traceable author statement. Source: Reactome

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 transcription, DNA-templated

Traceable author statement PubMed 8723388. 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_componentRISC complex

Inferred from direct assay Ref.14. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.16. 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_functiondouble-stranded RNA binding

Inferred from electronic annotation. Source: InterPro

miRNA binding

Inferred from electronic annotation. Source: UniProtKB-HAMAP

protein binding

Inferred from physical interaction Ref.14Ref.16. Source: UniProtKB

protein homodimerization activity

Inferred from physical interaction Ref.16. Source: UniProtKB

siRNA binding

Inferred from direct assay Ref.14. Source: UniProtKB

Complete GO annotation...

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 keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 366366RISC-loading complex subunit TARBP2 HAMAP-Rule MF_03034
PRO_0000065622

Regions

Domain30 – 9768DRBM 1
Domain159 – 22769DRBM 2
Domain293 – 36169DRBM 3
Region22 – 10584Sufficient for interaction with PRKRA HAMAP-Rule MF_03034
Region152 – 23483Sufficient for interaction with PRKRA HAMAP-Rule MF_03034
Region228 – 366139Sufficient for interaction with DICER1 HAMAP-Rule MF_03034
Region287 – 36680Sufficient for interaction with PRKRA HAMAP-Rule MF_03034

Natural variations

Alternative sequence1 – 2121Missing in isoform 2.
VSP_035584
Natural variant2511S → F. Ref.1 Ref.3
Corresponds to variant rs1126500 [ dbSNP | Ensembl ].
VAR_046992

Experimental info

Sequence conflict1441P → A in AAA36765. Ref.1

Secondary structure

..................... 366
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (TRBP2) [UniParc].

Last modified October 14, 2008. Version 3.
Checksum: 768BA11751DA4912

FASTA36639,039
        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 

« Hide

Isoform 2 (TRBP1) [UniParc].

Checksum: 7506A9324E9D0596
Show »

FASTA34536,916

References

« Hide '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. expand/collapse author list , 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 AGO2.
[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 AGO2.
[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 AGO2, 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; AGO2 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; AGO2; 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 AGO2.
[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.
CCDSCCDS41791.1. [Q15633-2]
CCDS8861.1. [Q15633-1]
PIRG01420.
RefSeqNP_004169.3. NM_004178.4. [Q15633-2]
NP_599150.1. NM_134323.1. [Q15633-1]
NP_599151.2. NM_134324.2. [Q15633-2]
XP_005269171.1. XM_005269114.1. [Q15633-2]
XP_005269172.1. XM_005269115.2. [Q15633-2]
UniGeneHs.326.
Hs.604255.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2CPNNMR-A150-225[»]
3ADLX-ray2.20A161-231[»]
3LLHX-ray2.14A/B22-105[»]
ProteinModelPortalQ15633.
SMRQ15633. Positions 28-225, 293-360.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112758. 18 interactions.
DIPDIP-29665N.
IntActQ15633. 10 interactions.
MINTMINT-92451.
STRING9606.ENSP00000266987.

Chemistry

BindingDBQ15633.

PTM databases

PhosphoSiteQ15633.

Polymorphism databases

DMDM209572714.

Proteomic databases

MaxQBQ15633.
PaxDbQ15633.
PRIDEQ15633.

Protocols and materials databases

DNASU6895.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000266987; ENSP00000266987; ENSG00000139546. [Q15633-1]
ENST00000394357; ENSP00000377885; ENSG00000139546. [Q15633-2]
ENST00000456234; ENSP00000416077; ENSG00000139546. [Q15633-2]
GeneID6895.
KEGGhsa:6895.
UCSCuc001sdo.3. human. [Q15633-1]

Organism-specific databases

CTD6895.
GeneCardsGC12P053890.
HGNCHGNC:11569. TARBP2.
HPAHPA051181.
MIM605053. gene.
neXtProtNX_Q15633.
PharmGKBPA36334.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG245126.
HOGENOMHOG000231919.
HOVERGENHBG001700.
InParanoidQ15633.
OMAIEQMLAV.
PhylomeDBQ15633.
TreeFamTF315953.

Enzyme and pathway databases

ReactomeREACT_71. Gene Expression.

Gene expression databases

ArrayExpressQ15633.
BgeeQ15633.
CleanExHS_TARBP2.
GenevestigatorQ15633.

Family and domain databases

Gene3D3.30.160.20. 3 hits.
HAMAPMF_03034. TRBP2.
InterProIPR014720. dsRNA-bd_dom.
IPR028605. TRBP2.
[Graphical view]
PANTHERPTHR10910:SF61. PTHR10910:SF61. 1 hit.
PfamPF00035. dsrm. 2 hits.
[Graphical view]
SMARTSM00358. DSRM. 3 hits.
[Graphical view]
PROSITEPS50137. DS_RBD. 3 hits.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ15633.
GeneWikiTARBP2.
GenomeRNAi6895.
NextBio26949.
PROQ15633.
SOURCESearch...

Entry information

Entry nameTRBP2_HUMAN
AccessionPrimary (citable) accession number: Q15633
Secondary accession number(s): Q12878 expand/collapse secondary AC list , Q8WY32, Q8WY33, Q9BRY2
Entry history
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: October 14, 2008
Last modified: July 9, 2014
This is version 135 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 12

Human chromosome 12: entries, gene names and cross-references to MIM