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Protein

Protein argonaute-3

Gene

AGO3

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

Functioni

Required for RNA-mediated gene silencing (RNAi). Binds to short RNAs such as microRNAs (miRNAs) and represses the translation of mRNAs which are complementary to them. Lacks endonuclease activity and does not appear to cleave target mRNAs. Proposed to be involved in stabilization of small RNA derivates (riRNA) derived from processed RNA polymerase III-transcribed Alu repeats containing a DR2 retinoic acid response element (RARE) in stem cells and in the subsequent riRNA-dependent degradation of a subset of RNA polymerase II-transcribed coding mRNAs by recruiting a mRNA decapping complex involving EDC4.UniRule annotation2 Publications

GO - Molecular functioni

  • double-stranded RNA binding Source: BHF-UCL
  • miRNA binding Source: BHF-UCL
  • RNA binding Source: UniProtKB
  • single-stranded RNA binding Source: BHF-UCL

GO - Biological processi

  • miRNA loading onto RISC involved in gene silencing by miRNA Source: BHF-UCL
  • miRNA mediated inhibition of translation Source: UniProtKB
  • mRNA catabolic process Source: UniProtKB
  • positive regulation of gene expression Source: Ensembl
  • positive regulation of NIK/NF-kappaB signaling Source: Ensembl
  • posttranscriptional gene silencing by RNA Source: Reactome
  • pre-miRNA processing Source: BHF-UCL
  • production of miRNAs involved in gene silencing by miRNA Source: BHF-UCL
  • regulation of megakaryocyte differentiation Source: Reactome
  • regulation of stem cell proliferation Source: UniProtKB
  • RNA secondary structure unwinding Source: BHF-UCL
  • Wnt signaling pathway, calcium modulating pathway Source: Reactome

Keywordsi

Molecular functionRibonucleoprotein, RNA-binding
Biological processRNA-mediated gene silencing, Translation regulation

Enzyme and pathway databases

ReactomeiR-HSA-1257604. PIP3 activates AKT signaling.
R-HSA-1912408. Pre-NOTCH Transcription and Translation.
R-HSA-203927. MicroRNA (miRNA) biogenesis.
R-HSA-2559580. Oxidative Stress Induced Senescence.
R-HSA-2559585. Oncogene Induced Senescence.
R-HSA-4086398. Ca2+ pathway.
R-HSA-426486. Small interfering RNA (siRNA) biogenesis.
R-HSA-426496. Post-transcriptional silencing by small RNAs.
R-HSA-5628897. TP53 Regulates Metabolic Genes.
R-HSA-5687128. MAPK6/MAPK4 signaling.
R-HSA-8934593. Regulation of RUNX1 Expression and Activity.
R-HSA-8936459. RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
R-HSA-8943723. Regulation of PTEN mRNA translation.
R-HSA-8948700. Competing endogenous RNAs (ceRNAs) regulate PTEN translation.

Names & Taxonomyi

Protein namesi
Recommended name:
Protein argonaute-3UniRule annotation
Short name:
Argonaute3UniRule annotation
Short name:
hAgo3
Alternative name(s):
Argonaute RISC catalytic component 3
Eukaryotic translation initiation factor 2C 3UniRule annotation
Short name:
eIF-2C 3UniRule annotation
Short name:
eIF2C 3UniRule annotation
Gene namesi
Name:AGO3
Synonyms:EIF2C3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000126070.19.
HGNCiHGNC:18421. AGO3.
MIMi607355. gene.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Organism-specific databases

DisGeNETi192669.
OpenTargetsiENSG00000126070.
PharmGKBiPA38329.

Polymorphism and mutation databases

BioMutaiAGO3.
DMDMi76803660.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001940611 – 860Protein argonaute-3Add BLAST860

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei825PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9H9G7.
MaxQBiQ9H9G7.
PaxDbiQ9H9G7.
PeptideAtlasiQ9H9G7.
PRIDEiQ9H9G7.

PTM databases

iPTMnetiQ9H9G7.
PhosphoSitePlusiQ9H9G7.

Expressioni

Gene expression databases

BgeeiENSG00000126070.
CleanExiHS_EIF2C3.
ExpressionAtlasiQ9H9G7. baseline and differential.
GenevisibleiQ9H9G7. HS.

Organism-specific databases

HPAiHPA048342.
HPA075436.

Interactioni

Subunit structurei

Interacts with EIF4B, IMP8, PRMT5 and TNRC6B. Interacts with APOBEC3F, APOBEC3G and APOBEC3H. Interacts with EDC4.UniRule annotation3 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi128177. 69 interactors.
DIPiDIP-54486N.
IntActiQ9H9G7. 57 interactors.
STRINGi9606.ENSP00000362287.

Structurei

Secondary structure

1860
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi27 – 40Combined sources14
Beta strandi47 – 52Combined sources6
Helixi60 – 73Combined sources14
Turni76 – 79Combined sources4
Beta strandi88 – 96Combined sources9
Beta strandi122 – 126Combined sources5
Beta strandi128 – 132Combined sources5
Helixi136 – 139Combined sources4
Beta strandi141 – 143Combined sources3
Helixi159 – 174Combined sources16
Beta strandi181 – 184Combined sources4
Beta strandi192 – 194Combined sources3
Beta strandi197 – 210Combined sources14
Beta strandi213 – 226Combined sources14
Helixi231 – 238Combined sources8
Helixi253 – 263Combined sources11
Beta strandi267 – 271Combined sources5
Beta strandi279 – 285Combined sources7
Turni290 – 292Combined sources3
Helixi309 – 315Combined sources7
Beta strandi328 – 332Combined sources5
Turni334 – 337Combined sources4
Beta strandi338 – 342Combined sources5
Beta strandi345 – 347Combined sources3
Helixi359 – 369Combined sources11
Helixi373 – 386Combined sources14
Helixi389 – 391Combined sources3
Helixi393 – 397Combined sources5
Beta strandi407 – 413Combined sources7
Turni423 – 425Combined sources3
Beta strandi452 – 456Combined sources5
Turni460 – 462Combined sources3
Helixi465 – 481Combined sources17
Beta strandi491 – 495Combined sources5
Beta strandi498 – 501Combined sources4
Helixi502 – 512Combined sources11
Beta strandi518 – 523Combined sources6
Helixi529 – 539Combined sources11
Helixi550 – 554Combined sources5
Helixi558 – 571Combined sources14
Helixi581 – 583Combined sources3
Helixi586 – 589Combined sources4
Beta strandi592 – 600Combined sources9
Beta strandi611 – 618Combined sources8
Beta strandi620 – 623Combined sources4
Beta strandi626 – 633Combined sources8
Helixi643 – 657Combined sources15
Beta strandi658 – 660Combined sources3
Beta strandi664 – 669Combined sources6
Helixi677 – 692Combined sources16
Turni693 – 695Combined sources3
Beta strandi702 – 707Combined sources6
Beta strandi716 – 719Combined sources4
Turni721 – 723Combined sources3
Turni726 – 729Combined sources4
Beta strandi735 – 737Combined sources3
Beta strandi739 – 742Combined sources4
Beta strandi744 – 752Combined sources9
Beta strandi764 – 771Combined sources8
Helixi777 – 788Combined sources12
Beta strandi792 – 796Combined sources5
Helixi802 – 812Combined sources11
Helixi815 – 818Combined sources4
Helixi839 – 845Combined sources7
Helixi851 – 853Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5VM9X-ray3.28A/C1-860[»]
ProteinModelPortaliQ9H9G7.
SMRiQ9H9G7.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini236 – 349PAZUniRule annotationAdd BLAST114
Domaini518 – 819PiwiUniRule annotationAdd BLAST302

Sequence similaritiesi

Belongs to the argonaute family. Ago subfamily.UniRule annotation

Phylogenomic databases

eggNOGiKOG1041. Eukaryota.
ENOG410XP07. LUCA.
GeneTreeiENSGT00760000119148.
HOGENOMiHOG000116043.
InParanoidiQ9H9G7.
KOiK11593.
OMAiQPANPQY.
OrthoDBiEOG091G020J.
PhylomeDBiQ9H9G7.
TreeFamiTF101510.

Family and domain databases

Gene3Di3.30.420.10. 1 hit.
HAMAPiMF_03032. AGO3. 1 hit.
InterProiView protein in InterPro
IPR028603. AGO3.
IPR014811. ArgoL1.
IPR032472. ArgoL2.
IPR032473. Argonaute_Mid_dom.
IPR032474. Argonaute_N.
IPR003100. PAZ_dom.
IPR036085. PAZ_dom_sf.
IPR003165. Piwi.
IPR012337. RNaseH-like_sf.
IPR036397. RNaseH_sf.
PfamiView protein in Pfam
PF08699. ArgoL1. 1 hit.
PF16488. ArgoL2. 1 hit.
PF16487. ArgoMid. 1 hit.
PF16486. ArgoN. 1 hit.
PF02170. PAZ. 1 hit.
PF02171. Piwi. 1 hit.
SMARTiView protein in SMART
SM01163. DUF1785. 1 hit.
SM00949. PAZ. 1 hit.
SM00950. Piwi. 1 hit.
SUPFAMiSSF101690. SSF101690. 1 hit.
SSF53098. SSF53098. 1 hit.
PROSITEiView protein in PROSITE
PS50821. PAZ. 1 hit.
PS50822. PIWI. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q9H9G7-1) [UniParc]FASTAAdd to basket

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
MEIGSAGPAG AQPLLMVPRR PGYGTMGKPI KLLANCFQVE IPKIDVYLYE
60 70 80 90 100
VDIKPDKCPR RVNREVVDSM VQHFKVTIFG DRRPVYDGKR SLYTANPLPV
110 120 130 140 150
ATTGVDLDVT LPGEGGKDRP FKVSIKFVSR VSWHLLHEVL TGRTLPEPLE
160 170 180 190 200
LDKPISTNPV HAVDVVLRHL PSMKYTPVGR SFFSAPEGYD HPLGGGREVW
210 220 230 240 250
FGFHQSVRPA MWKMMLNIDV SATAFYKAQP VIQFMCEVLD IHNIDEQPRP
260 270 280 290 300
LTDSHRVKFT KEIKGLKVEV THCGTMRRKY RVCNVTRRPA SHQTFPLQLE
310 320 330 340 350
NGQTVERTVA QYFREKYTLQ LKYPHLPCLQ VGQEQKHTYL PLEVCNIVAG
360 370 380 390 400
QRCIKKLTDN QTSTMIKATA RSAPDRQEEI SRLVRSANYE TDPFVQEFQF
410 420 430 440 450
KVRDEMAHVT GRVLPAPMLQ YGGRNRTVAT PSHGVWDMRG KQFHTGVEIK
460 470 480 490 500
MWAIACFATQ RQCREEILKG FTDQLRKISK DAGMPIQGQP CFCKYAQGAD
510 520 530 540 550
SVEPMFRHLK NTYSGLQLII VILPGKTPVY AEVKRVGDTL LGMATQCVQV
560 570 580 590 600
KNVIKTSPQT LSNLCLKINV KLGGINNILV PHQRPSVFQQ PVIFLGADVT
610 620 630 640 650
HPPAGDGKKP SIAAVVGSMD AHPSRYCATV RVQRPRQEII QDLASMVREL
660 670 680 690 700
LIQFYKSTRF KPTRIIFYRD GVSEGQFRQV LYYELLAIRE ACISLEKDYQ
710 720 730 740 750
PGITYIVVQK RHHTRLFCAD RTERVGRSGN IPAGTTVDTD ITHPYEFDFY
760 770 780 790 800
LCSHAGIQGT SRPSHYHVLW DDNCFTADEL QLLTYQLCHT YVRCTRSVSI
810 820 830 840 850
PAPAYYAHLV AFRARYHLVD KEHDSAEGSH VSGQSNGRDP QALAKAVQIH
860
QDTLRTMYFA
Length:860
Mass (Da):97,360
Last modified:September 27, 2005 - v2
Checksum:i6FF1277995E5322E
GO
Isoform 2 (identifier: Q9H9G7-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-234: Missing.

Show »
Length:626
Mass (Da):71,211
Checksum:i5475FD0337AAD9CE
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti25T → A in BAB14262 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0410841 – 234Missing in isoform 2. 1 PublicationAdd BLAST234

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK022827 mRNA. Translation: BAB14262.1.
AL139286 Genomic DNA. No translation available.
AL138787 Genomic DNA. No translation available.
BC025769 mRNA. No translation available.
CCDSiCCDS399.1. [Q9H9G7-1]
CCDS400.1. [Q9H9G7-2]
RefSeqiNP_079128.2. NM_024852.3. [Q9H9G7-1]
NP_803171.1. NM_177422.2. [Q9H9G7-2]
XP_005270632.1. XM_005270575.3. [Q9H9G7-1]
XP_011539184.1. XM_011540882.2. [Q9H9G7-2]
XP_016856012.1. XM_017000523.1. [Q9H9G7-1]
XP_016856013.1. XM_017000524.1. [Q9H9G7-2]
XP_016856014.1. XM_017000525.1. [Q9H9G7-2]
XP_016856015.1. XM_017000526.1. [Q9H9G7-2]
XP_016856016.1. XM_017000527.1. [Q9H9G7-2]
UniGeneiHs.657659.

Genome annotation databases

EnsembliENST00000246314; ENSP00000246314; ENSG00000126070. [Q9H9G7-2]
ENST00000373191; ENSP00000362287; ENSG00000126070. [Q9H9G7-1]
GeneIDi192669.
KEGGihsa:192669.
UCSCiuc001bzp.4. human. [Q9H9G7-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiAGO3_HUMAN
AccessioniPrimary (citable) accession number: Q9H9G7
Secondary accession number(s): B1ALI0, Q5TA55, Q9H1U6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 14, 2003
Last sequence update: September 27, 2005
Last modified: January 31, 2018
This is version 131 of the entry and version 2 of the sequence. See 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 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. Translation initiation factors
    List of translation initiation factor entries
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families