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Protein

RISC-loading complex subunit TARBP2

Gene

TARBP2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.UniRule annotation9 Publications

GO - Molecular functioni

  • double-stranded RNA binding Source: BHF-UCL
  • enzyme binding Source: BHF-UCL
  • miRNA binding Source: UniProtKB-HAMAP
  • pre-miRNA binding Source: BHF-UCL
  • pre-mRNA binding Source: BHF-UCL
  • protein homodimerization activity Source: UniProtKB
  • protein N-terminus binding Source: BHF-UCL
  • siRNA binding Source: UniProtKB

GO - Biological processi

  • gene silencing by RNA Source: Reactome
  • miRNA loading onto RISC involved in gene silencing by miRNA Source: BHF-UCL
  • multicellular organism growth Source: Ensembl
  • negative regulation of defense response to virus by host Source: UniProtKB
  • negative regulation of protein kinase activity Source: UniProtKB
  • positive regulation of translation Source: Ensembl
  • positive regulation of viral genome replication Source: UniProtKB
  • pre-miRNA processing Source: UniProtKB
  • production of miRNAs involved in gene silencing by miRNA Source: UniProtKB
  • production of siRNA involved in RNA interference Source: UniProtKB
  • regulation of viral transcription Source: UniProtKB
  • single fertilization Source: Ensembl
  • siRNA loading onto RISC involved in RNA interference Source: UniProtKB
  • spermatid development Source: Ensembl
  • targeting of mRNA for destruction involved in RNA interference Source: UniProtKB
Complete GO annotation...

Keywords - Biological processi

RNA-mediated gene silencing, Translation regulation

Keywords - Ligandi

RNA-binding

Enzyme and pathway databases

BioCyciZFISH:ENSG00000139546-MONOMER.
ReactomeiR-HSA-203927. MicroRNA (miRNA) biogenesis.
R-HSA-426486. Small interfering RNA (siRNA) biogenesis.
SIGNORiQ15633.

Names & Taxonomyi

Protein namesi
Recommended name:
RISC-loading complex subunit TARBP2UniRule annotation
Alternative name(s):
TAR RNA-binding protein 2
Trans-activation-responsive RNA-binding protein
Gene namesi
Name:TARBP2UniRule annotation
Synonyms:TRBP
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:11569. TARBP2.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: Reactome
  • micro-ribonucleoprotein complex Source: Ensembl
  • nucleus Source: HPA
  • perinuclear region of cytoplasm Source: UniProtKB-SubCell
  • RISC complex Source: UniProtKB-HAMAP
  • RISC-loading complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi6895.
OpenTargetsiENSG00000139546.
PharmGKBiPA36334.

Polymorphism and mutation databases

BioMutaiTARBP2.
DMDMi209572714.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000656221 – 366RISC-loading complex subunit TARBP2Add BLAST366

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei152PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ15633.
MaxQBiQ15633.
PaxDbiQ15633.
PeptideAtlasiQ15633.
PRIDEiQ15633.

PTM databases

iPTMnetiQ15633.
PhosphoSitePlusiQ15633.

Expressioni

Gene expression databases

BgeeiENSG00000139546.
CleanExiHS_TARBP2.
ExpressionAtlasiQ15633. baseline and differential.
GenevisibleiQ15633. HS.

Organism-specific databases

HPAiCAB069406.
HPA051181.
HPA061454.

Interactioni

Subunit structurei

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) (PubMed:17507929).UniRule annotation11 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-978581,EBI-978581
ADARP55265-12EBI-978581,EBI-6913056
ADARP55265-53EBI-978581,EBI-6913210
AGO2Q9UKV85EBI-978581,EBI-528269
DICER1Q9UPY321EBI-978581,EBI-395506
EIF2AK2P195252EBI-978581,EBI-640775
PRKRAO755699EBI-978581,EBI-713955
STRBPQ96SI93EBI-978581,EBI-740355
TCEANCQ8N8B73EBI-978581,EBI-954696
ZNF346Q9UL403EBI-978581,EBI-2462313

GO - Molecular functioni

  • enzyme binding Source: BHF-UCL
  • protein homodimerization activity Source: UniProtKB
  • protein N-terminus binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi112758. 66 interactors.
DIPiDIP-29665N.
IntActiQ15633. 27 interactors.
MINTiMINT-92451.
STRINGi9606.ENSP00000266987.

Structurei

Secondary structure

1366
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi31 – 41Combined sources11
Beta strandi47 – 53Combined sources7
Beta strandi62 – 68Combined sources7
Beta strandi71 – 79Combined sources9
Helixi80 – 95Combined sources16
Helixi161 – 170Combined sources10
Beta strandi177 – 185Combined sources9
Beta strandi187 – 189Combined sources3
Beta strandi191 – 198Combined sources8
Beta strandi201 – 209Combined sources9
Helixi210 – 226Combined sources17
Beta strandi291 – 293Combined sources3
Helixi294 – 305Combined sources12
Beta strandi309 – 316Combined sources8
Beta strandi323 – 329Combined sources7
Beta strandi331 – 333Combined sources3
Beta strandi335 – 343Combined sources9
Helixi344 – 362Combined sources19

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2CPNNMR-A150-225[»]
3ADLX-ray2.20A161-231[»]
3LLHX-ray2.14A/B22-105[»]
4WYQX-ray3.20B/E289-363[»]
ProteinModelPortaliQ15633.
SMRiQ15633.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ15633.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini30 – 97DRBM 1UniRule annotationAdd BLAST68
Domaini159 – 227DRBM 2UniRule annotationAdd BLAST69
Domaini293 – 361DRBM 3UniRule annotationAdd BLAST69

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni22 – 105Sufficient for interaction with PRKRAAdd BLAST84
Regioni152 – 234Sufficient for interaction with PRKRAAdd BLAST83
Regioni228 – 366Sufficient for interaction with DICER1Add BLAST139
Regioni287 – 366Sufficient for interaction with PRKRAAdd BLAST80

Sequence similaritiesi

Belongs to the TARBP2 family.UniRule annotation
Contains 3 DRBM (double-stranded RNA-binding) domains.UniRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3732. Eukaryota.
ENOG410XSCK. LUCA.
GeneTreeiENSGT00830000128290.
HOGENOMiHOG000231919.
HOVERGENiHBG001700.
InParanoidiQ15633.
KOiK18420.
OMAiSCTWDSL.
OrthoDBiEOG091G0I2L.
PhylomeDBiQ15633.
TreeFamiTF315953.

Family and domain databases

Gene3Di3.30.160.20. 3 hits.
HAMAPiMF_03034. TRBP2. 1 hit.
InterProiIPR014720. dsRBD_dom.
IPR028605. TRBP2.
[Graphical view]
PANTHERiPTHR10910:SF61. PTHR10910:SF61. 1 hit.
PfamiPF00035. dsrm. 2 hits.
[Graphical view]
SMARTiSM00358. DSRM. 3 hits.
[Graphical view]
PROSITEiPS50137. DS_RBD. 3 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative promoter usage. AlignAdd to basket

Isoform 1 (identifier: Q15633-1) [UniParc]FASTAAdd to basket
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.

« Hide

        10         20         30         40         50
MSEEEQGSGT TTGCGLPSIE QMLAANPGKT PISLLQEYGT RIGKTPVYDL
60 70 80 90 100
LKAEGQAHQP NFTFRVTVGD TSCTGQGPSK KAAKHKAAEV ALKHLKGGSM
110 120 130 140 150
LEPALEDSSS FSPLDSSLPE DIPVFTAAAA ATPVPSVVLT RSPPMELQPP
160 170 180 190 200
VSPQQSECNP VGALQELVVQ KGWRLPEYTV TQESGPAHRK EFTMTCRVER
210 220 230 240 250
FIEIGSGTSK KLAKRNAAAK MLLRVHTVPL DARDGNEVEP DDDHFSIGVG
260 270 280 290 300
SRLDGLRNRG PGCTWDSLRN SVGEKILSLR SCSLGSLGAL GPACCRVLSE
310 320 330 340 350
LSEEQAFHVS YLDIEELSLS GLCQCLVELS TQPATVCHGS ATTREAARGE
360
AARRALQYLK IMAGSK
Length:366
Mass (Da):39,039
Last modified:October 14, 2008 - v3
Checksum:i768BA11751DA4912
GO
Isoform 2 (identifier: Q15633-2) [UniParc]FASTAAdd to basket
Also known as: TRBP1

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

Show »
Length:345
Mass (Da):36,916
Checksum:i7506A9324E9D0596
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti144P → A in AAA36765 (PubMed:2011739).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_046992251S → F.2 PublicationsCorresponds to variant rs1126500dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0355841 – 21Missing in isoform 2. 1 PublicationAdd BLAST21

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS41791.1. [Q15633-2]
CCDS8861.1. [Q15633-1]
PIRiG01420.
RefSeqiNP_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]
UniGeneiHs.326.
Hs.604255.

Genome annotation databases

EnsembliENST00000266987; ENSP00000266987; ENSG00000139546. [Q15633-1]
ENST00000394357; ENSP00000377885; ENSG00000139546. [Q15633-2]
ENST00000456234; ENSP00000416077; ENSG00000139546. [Q15633-2]
GeneIDi6895.
KEGGihsa:6895.
UCSCiuc001sdo.4. human. [Q15633-1]

Keywords - Coding sequence diversityi

Alternative promoter usage, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS41791.1. [Q15633-2]
CCDS8861.1. [Q15633-1]
PIRiG01420.
RefSeqiNP_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]
UniGeneiHs.326.
Hs.604255.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2CPNNMR-A150-225[»]
3ADLX-ray2.20A161-231[»]
3LLHX-ray2.14A/B22-105[»]
4WYQX-ray3.20B/E289-363[»]
ProteinModelPortaliQ15633.
SMRiQ15633.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112758. 66 interactors.
DIPiDIP-29665N.
IntActiQ15633. 27 interactors.
MINTiMINT-92451.
STRINGi9606.ENSP00000266987.

PTM databases

iPTMnetiQ15633.
PhosphoSitePlusiQ15633.

Polymorphism and mutation databases

BioMutaiTARBP2.
DMDMi209572714.

Proteomic databases

EPDiQ15633.
MaxQBiQ15633.
PaxDbiQ15633.
PeptideAtlasiQ15633.
PRIDEiQ15633.

Protocols and materials databases

DNASUi6895.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000266987; ENSP00000266987; ENSG00000139546. [Q15633-1]
ENST00000394357; ENSP00000377885; ENSG00000139546. [Q15633-2]
ENST00000456234; ENSP00000416077; ENSG00000139546. [Q15633-2]
GeneIDi6895.
KEGGihsa:6895.
UCSCiuc001sdo.4. human. [Q15633-1]

Organism-specific databases

CTDi6895.
DisGeNETi6895.
GeneCardsiTARBP2.
HGNCiHGNC:11569. TARBP2.
HPAiCAB069406.
HPA051181.
HPA061454.
MIMi605053. gene.
neXtProtiNX_Q15633.
OpenTargetsiENSG00000139546.
PharmGKBiPA36334.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3732. Eukaryota.
ENOG410XSCK. LUCA.
GeneTreeiENSGT00830000128290.
HOGENOMiHOG000231919.
HOVERGENiHBG001700.
InParanoidiQ15633.
KOiK18420.
OMAiSCTWDSL.
OrthoDBiEOG091G0I2L.
PhylomeDBiQ15633.
TreeFamiTF315953.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000139546-MONOMER.
ReactomeiR-HSA-203927. MicroRNA (miRNA) biogenesis.
R-HSA-426486. Small interfering RNA (siRNA) biogenesis.
SIGNORiQ15633.

Miscellaneous databases

EvolutionaryTraceiQ15633.
GeneWikiiTARBP2.
GenomeRNAii6895.
PROiQ15633.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000139546.
CleanExiHS_TARBP2.
ExpressionAtlasiQ15633. baseline and differential.
GenevisibleiQ15633. HS.

Family and domain databases

Gene3Di3.30.160.20. 3 hits.
HAMAPiMF_03034. TRBP2. 1 hit.
InterProiIPR014720. dsRBD_dom.
IPR028605. TRBP2.
[Graphical view]
PANTHERiPTHR10910:SF61. PTHR10910:SF61. 1 hit.
PfamiPF00035. dsrm. 2 hits.
[Graphical view]
SMARTiSM00358. DSRM. 3 hits.
[Graphical view]
PROSITEiPS50137. DS_RBD. 3 hits.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiTRBP2_HUMAN
AccessioniPrimary (citable) accession number: Q15633
Secondary accession number(s): Q12878
, Q8WY32, Q8WY33, Q9BRY2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: October 14, 2008
Last modified: November 30, 2016
This is version 161 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 12
    Human chromosome 12: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.