AGO3 – Protein argonaute-3 – Homo sapiens (Human)

Or you want a quick look: AGO3

AGO3

Homo sapiens (Human)

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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 (siRNA) derived from processed RNA polymerase III-transcribed Alu repeats containing a DR2 retinoic acid response element (RARE) in stem cells and in the subsequent siRNA-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:updating).

Catalytic activityi

  • Endonucleolytic cleavage to 5'-phosphomonoester. EC:3.1.26.n2

Sites

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

GO - Molecular functioni

  • double-stranded RNA binding
  • endoribonuclease activity
  • endoribonuclease activity, cleaving miRNA-paired mRNA
  • metal ion binding
  • miRNA binding
  • RNA binding
  • single-stranded RNA binding

GO - Biological processi

  • intracellular receptor signaling pathway
  • miRNA loading onto RISC involved in gene silencing by miRNA
  • miRNA mediated inhibition of translation
  • mRNA catabolic process
  • negative regulation of gene expression
  • positive regulation of gene expression
  • positive regulation of NIK/NF-kappaB signaling
  • post-transcriptional gene silencing by RNA
  • pre-miRNA processing
  • production of miRNAs involved in gene silencing by miRNA
  • regulation of megakaryocyte differentiation
  • regulation of stem cell proliferation
  • regulation of transcription initiation from RNA polymerase II promoter
  • RNA secondary structure unwinding
  • Wnt signaling pathway, calcium modulating pathway

Keywordsi

Enzyme and pathway databases

PathwayCommonsiQ9H9G7

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-8853884, Transcriptional Regulation by VENTX

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-8986944, Transcriptional Regulation by MECP2

R-HSA-9018519, Estrogen-dependent gene expression

R-HSA-9022692, Regulation of MECP2 expression and activity

R-HSA-9029569, NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux

Names & Taxonomyi

Organism-specific databases

Pathology & Biotechi

Mutagenesis

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

Organism-specific databases

Miscellaneous databases

Genetic variation databases

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-acetylmethionine1
Modified residuei825Phosphoserine1

Post-translational modificationi

Ubiquitinated on surface-exposed lysines by a SCF-like E3 ubiquitin-protein ligase complex containing ZSWIM8 during target-directed microRNA degradation (TDMD), a process that mediates degradation of microRNAs (miRNAs). Ubiquitination by the SCF-like E3 ubiquitin-protein ligase complex containing ZSWIM8 leads to its subsequent degradation, thereby exposing miRNAs for degradation. ZSWIM8 recognizes and binds AGO3 when it is engaged with a TDMD target.

Keywords - PTMi

Acetylation, Phosphoprotein, Ubl conjugation

Proteomic databases

PTM databases

Expressioni

Gene expression databases

BgeeiENSGupdating, Expressed in buccal mucosa cell and 222 other tissues

ExpressionAtlasiQ9H9G7, baseline and differential

GenevisibleiQ9H9G7, HS

Organism-specific databases

Interactioni

Subunit structurei

Interacts with EIF4B, IMP8, PRMT5 and TNRC6B.

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Interacts with APOBEC3F, APOBEC3G and APOBEC3H.

Interacts with EDC4.

Binary interactionsi

Hide details

Protein-protein interaction databases

Miscellaneous databases

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini236 – 349PAZAdd BLAST114
Domaini518 – 819PiwiAdd BLAST302

Region

Sequence similaritiesi

Phylogenomic databases

Family and domain databases

Gene3Diupdating, 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

This entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All

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

This isoform has been chosen as the canonicali 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

 updating

MEIGSAGPAG AQPLLMVPRR PGYGTMGKPI KLLANCFQVE IPKIDVYLYE

updating

VDIKPDKCPR RVNREVVDSM VQHFKVTIFG DRRPVYDGKR SLYTANPLPV

updating

ATTGVDLDVT LPGEGGKDRP FKVSIKFVSR VSWHLLHEVL TGRTLPEPLE

updating

LDKPISTNPV HAVDVVLRHL PSMKYTPVGR SFFSAPEGYD HPLGGGREVW

updating

FGFHQSVRPA MWKMMLNIDV SATAFYKAQP VIQFMCEVLD IHNIDEQPRP

updating

LTDSHRVKFT KEIKGLKVEV THCGTMRRKY RVCNVTRRPA SHQTFPLQLE

updating

NGQTVERTVA QYFREKYTLQ LKYPHLPCLQ VGQEQKHTYL PLEVCNIVAG

updating

QRCIKKLTDN QTSTMIKATA RSAPDRQEEI SRLVRSANYE TDPFVQEFQF

updating

KVRDEMAHVT GRVLPAPMLQ YGGRNRTVAT PSHGVWDMRG KQFHTGVEIK

updating

MWAIACFATQ RQCREEILKG FTDQLRKISK DAGMPIQGQP CFCKYAQGAD

updating

SVEPMFRHLK NTYSGLQLII VILPGKTPVY AEVKRVGDTL LGMATQCVQV

updating

KNVIKTSPQT LSNLCLKINV KLGGINNILV PHQRPSVFQQ PVIFLGADVT

updating

HPPAGDGKKP SIAAVVGSMD AHPSRYCATV RVQRPRQEII QDLASMVREL

updating

LIQFYKSTRF KPTRIIFYRD GVSEGQFRQV LYYELLAIRE ACISLEKDYQ

updating

PGITYIVVQK RHHTRLFCAD RTERVGRSGN IPAGTTVDTD ITHPYEFDFY

updating

LCSHAGIQGT SRPSHYHVLW DDNCFTADEL QLLTYQLCHT YVRCTRSVSI

updating

PAPAYYAHLV AFRARYHLVD KEHDSAEGSH VSGQSNGRDP QALAKAVQIH

860

QDTLRTMYFA

860

97,360

September 27, 2005 - v2

6FF1277995E5322E

GO

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626

71,211

5475FD0337AAD9CE

GO

There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket

Q5TA56Q5TA56_HUMAN

Eukaryotic translation initiation f...

AGO3 EIF2C3, hCG_1640521

229Annotation score:
A0A0U1RR19A0A0U1RR19_HUMAN

Protein argonaute-3

AGO3

64Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti25T → A in BAB14262 (PubMed:14702039).1

Alternative sequence

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

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

3D structure databases

Select the link destinations:

PDBei

RCSB PDBi

PDBji

Links Updated

PDB entryMethodResolution (Å)ChainPositionsPDBsum
5VM9X-ray3.28A/C1-860[»]
SMRiQ9H9G7

ModBaseiSearch...

PDBe-KBiSearch...

Protein-protein interaction databases

PTM databases

Genetic variation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

PathwayCommonsiQ9H9G7

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-8853884, Transcriptional Regulation by VENTX

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-8986944, Transcriptional Regulation by MECP2

R-HSA-9018519, Estrogen-dependent gene expression

R-HSA-9022692, Regulation of MECP2 expression and activity

R-HSA-9029569, NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux

Miscellaneous databases

Gene expression databases

BgeeiENSGupdating, Expressed in buccal mucosa cell and 222 other tissues

ExpressionAtlasiQ9H9G7, baseline and differential

GenevisibleiQ9H9G7, HS

Family and domain databases

Gene3Diupdating, 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

MobiDBiSearch...

Entry informationi

Entry nameiAGO3_HUMAN
AccessioniQ9H9G7Primary (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: June 2, 2021
This is version 155 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.
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