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Protein

Protein argonaute-3

Gene

AGO3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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. 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. Possesses RNA slicer activity but only on select RNAs bearing 5'- and 3'-flanking sequences to the region of guide-target complementarity (PubMed:29040713).UniRule annotation3 Publications

Catalytic activityi

Endonucleolytic cleavage to 5'-phosphomonoester.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi598Divalent metal cation1 Publication1
Metal bindingi638Divalent metal cation1 Publication1
Metal bindingi670Divalent metal cation1 Publication1
Metal bindingi808Divalent metal cation1 Publication1

GO - Molecular functioni

  • double-stranded RNA binding Source: BHF-UCL
  • endoribonuclease activity Source: UniProtKB
  • endoribonuclease activity, cleaving miRNA-paired mRNA Source: UniProtKB
  • metal ion binding Source: UniProtKB-KW
  • 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 functionEndonuclease, Hydrolase, Nuclease, Ribonucleoprotein, RNA-binding
Biological processRNA-mediated gene silencing, Translation regulation
LigandMetal-binding

Enzyme and pathway databases

ReactomeiR-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
R-HSA-9018519 Estrogen-dependent gene expression

Names & Taxonomyi

Protein namesi
Recommended name:
Protein argonaute-3UniRule annotation (EC:3.1.26.n21 Publication)
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
neXtProtiNX_Q9H9G7

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

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi638E → A: Loss of RNA slicer activity. 1 Publication1

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
ProteomicsDBi81320
81321 [Q9H9G7-2]

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, 70 interactors
DIPiDIP-54486N
IntActiQ9H9G7, 60 interactors
MINTiQ9H9G7
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

ProteinModelPortaliQ9H9G7
SMRiQ9H9G7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

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

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni530 – 567Interaction with guide RNA1 PublicationAdd BLAST38
Regioni758 – 805Interaction with guide RNA1 PublicationAdd BLAST48

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: July 18, 2018
This is version 136 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

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