AGO3 argonaute RISC catalytic component 3 [Homo sapiens (human)] - Gene

Summary

Official Symbol: AGO3provided by HGNC
Official Full Name: argonaute RISC catalytic component 3provided by HGNC
Primary source: HGNC:HGNC:18421
See related: Ensembl:ENSG00000126070 MIM:607355; AllianceGenome:HGNC:18421
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: EIF2C3
Summary: This gene encodes a member of the Argonaute family of proteins which play a role in RNA interference. The encoded protein is highly basic, contains a PAZ domain and a PIWI domain, and may play a role in short-interfering-RNA-mediated gene silencing. This gene is located on chromosome 1 in a tandem cluster of closely related family members including argonaute 4 and eukaryotic translation initiation factor 2C, 1. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in skin (RPKM 1.4), testis (RPKM 1.4) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p34.3

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (35930718..36072500)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (35793433..35935374)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (36396706..36538101)

Chromosome 1 - NC_000001.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Argonaute 3 (AGO3) promotes malignancy potential of cervical cancer via regulation of Wnt/beta-catenin signaling pathway.
Title: Argonaute 3 (AGO3) promotes malignancy potential of cervical cancer via regulation of Wnt/β-catenin signaling pathway.
Human Argonaute2 and Argonaute3 are catalytically activated by different lengths of guide RNA.
Title: Human Argonaute2 and Argonaute3 are catalytically activated by different lengths of guide RNA.
Data show that recombinant AGO3 loaded with miR-20a cleaves complementary target RNAs.
Title: Human Argonaute3 has slicer activity.
Study uncovers a first example of a vertebrate protein factor, Argonaute-3, specifically affecting the guide-to-passenger-strand ratio of the miRNA let-7a. A multi-layered mechanism for the observed impact of Ago3 on the let-7a-3p passenger strand expression and activity is proposed.
Title: Argonaute-3 activates the let-7a passenger strand microRNA.
The N-terminal domain of Ago3 inhibits cleavage activity. AAs 1-64 are largely unstructured & form a large loop surrounding an area containing two helices & another unstructured loop.
Title: Turning catalytically inactive human Argonaute proteins into active slicer enzymes.
The Ago3 PIWI domain is slicing competent but our Ago3 model suggests multiple interactions between residues in the PIWI & N domains that may increase protein rigidity or invoke other properties that contribute to Ago3's observed slicing deficiency.
Title: Molecular dissection of human Argonaute proteins by DNA shuffling.
DICER- and AGO3-dependent generation of retinoic acid-induced DR2 Alu RNAs regulates human stem cell proliferation.
Title: DICER- and AGO3-dependent generation of retinoic acid-induced DR2 Alu RNAs regulates human stem cell proliferation.
Ago3 is able to load microRNAs efficiently in the absence of Ago1 and Ago2, despite a significant loss of global microRNA expression
Title: Quantitative functions of Argonaute proteins in mammalian development.
reliable predictions of miRNA affinity to Ago2 AND Ago3 proteins were made.
Title: [The nucleotide sequence features of the mature microRNA seem to be responsible for the affinity to human Ago2 AND Ago3 proteins].
EIF@C3 protein is expressed in both Schwann and neuron-type differentiating cells.
Title: Differential expression of Dicer and Argonaute genes during the differentiation of human neuroblastoma cells.

Submit: New GeneRIF Correction See all GeneRIFs (11)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of eukaryotic translation initiation factor 2C, 3 (EIF2C3) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH102469 (e-PCR)
- UniSTS:96803

SHGC-74579 (e-PCR)
- UniSTS:44843

SHGC-141728 (e-PCR)
- UniSTS:171054

SHGC-74570 (e-PCR)
- UniSTS:47496

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables RNA binding	HDA more info	PubMed
enables RNA endonuclease activity	IBA Inferred from Biological aspect of Ancestor more info
enables RNA endonuclease activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables double-stranded RNA binding	IDA Inferred from Direct Assay more info	PubMed
enables endoribonuclease activity, cleaving miRNA-paired mRNA	IMP Inferred from Mutant Phenotype more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables miRNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables miRNA binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables single-stranded RNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables single-stranded RNA binding	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in RISC complex assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in RNA secondary structure unwinding	IDA Inferred from Direct Assay more info	PubMed
involved_in RNA secondary structure unwinding	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in mRNA catabolic process	IDA Inferred from Direct Assay more info	PubMed
involved_in miRNA processing	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in miRNA-mediated gene silencing by inhibition of translation	IDA Inferred from Direct Assay more info	PubMed
NOT involved_in miRNA-mediated gene silencing by mRNA destabilization	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of gene expression	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of non-canonical NF-kappaB signal transduction	IEA Inferred from Electronic Annotation more info
involved_in pre-miRNA processing	IBA Inferred from Biological aspect of Ancestor more info
involved_in pre-miRNA processing	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of stem cell proliferation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulatory ncRNA-mediated post-transcriptional gene silencing	IBA Inferred from Biological aspect of Ancestor more info
NOT involved_in siRNA-mediated gene silencing by mRNA destabilization	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in P-body	IEA Inferred from Electronic Annotation more info
part_of RISC complex	IBA Inferred from Biological aspect of Ancestor more info
part_of RISC complex	IDA Inferred from Direct Assay more info	PubMed
part_of RISC-loading complex	IDA Inferred from Direct Assay more info	PubMed
located_in condensed nuclear chromosome	IEA Inferred from Electronic Annotation more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
is_active_in cytoplasmic ribonucleoprotein granule	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasmic ribonucleoprotein granule	IDA Inferred from Direct Assay more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in membrane	HDA more info	PubMed
located_in nucleoplasm	IDA Inferred from Direct Assay more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: protein argonaute-3

Names: argonaute 3, RISC catalytic component; eukaryotic translation initiation factor 2C, 3; hAgo3

NP_079128.2

EC 3.1.26.n2

NP_803171.1

EC 3.1.26.n2

XP_005270632.1

EC 3.1.26.n2

XP_005270633.1

EC 3.1.26.n2

XP_011539181.1

EC 3.1.26.n2

XP_016856012.1

EC 3.1.26.n2

XP_016856013.1

EC 3.1.26.n2

XP_016856015.1

EC 3.1.26.n2

XP_047304090.1

EC 3.1.26.n2

XP_054190794.1

EC 3.1.26.n2

XP_054190795.1

EC 3.1.26.n2

XP_054190796.1

EC 3.1.26.n2

XP_054190797.1

EC 3.1.26.n2

XP_054190798.1

EC 3.1.26.n2

XP_054190799.1

EC 3.1.26.n2

XP_054190800.1

EC 3.1.26.n2

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_024852.4 → NP_079128.2 protein argonaute-3 isoform a

See identical proteins and their annotated locations for NP_079128.2

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript, and encodes the longer isoform (a).

Source sequence(s)

AA251146, AK303929, AL138787, AL139286, BF979526, BX104163

Consensus CDS

CCDS399.1

UniProtKB/Swiss-Prot

B1ALI0, Q5TA55, Q9H1U6, Q9H9G7

UniProtKB/TrEMBL

A8KA05

Related

ENSP00000362287.3, ENST00000373191.9

Conserved Domains (4) summary

cd02846
Location:228 → 348

PAZ_argonaute_like; PAZ domain, argonaute_like subfamily. Argonaute is part of the RNA-induced silencing complex (RISC), and is an endonuclease that plays a key role in the RNA interference pathway. The PAZ domain has been named after the proteins Piwi,Argonaut, and Zwille. ...

cd04657
Location:393 → 818

Piwi_ago-like; PIWI domain, Argonaute-like subfamily. Argonaute is the central component of the RNA-induced silencing complex (RISC) and related complexes. The PIWI domain is the C-terminal portion of Argonaute and consists of two subdomains, one of which provides the ...

pfam08699
Location:177 → 227

ArgoL1; Argonaute linker 1 domain

pfam16486
Location:73 → 167

ArgoN; N-terminal domain of argonaute
NM_177422.3 → NP_803171.1 protein argonaute-3 isoform b

See identical proteins and their annotated locations for NP_803171.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) has multiple differences in the coding region, which causes translation initiation at a downstream start codon, compared to variant 1. The resulting protein (isoform b) has a shorter N-terminus than isoform a.

Source sequence(s)

AA251146, AL138787, BC025769, BF979526, BX104163

Consensus CDS

CCDS400.1

UniProtKB/TrEMBL

B4E1P5

Related

ENSP00000246314.6, ENST00000246314.10

Conserved Domains (2) summary

cd02846
Location:1 → 114

PAZ_argonaute_like; PAZ domain, argonaute_like subfamily. Argonaute is part of the RNA-induced silencing complex (RISC), and is an endonuclease that plays a key role in the RNA interference pathway. The PAZ domain has been named after the proteins Piwi,Argonaut, and Zwille. ...

cd04657
Location:159 → 584

Piwi_ago-like; PIWI domain, Argonaute-like subfamily. Argonaute is the central component of the RNA-induced silencing complex (RISC) and related complexes. The PIWI domain is the C-terminal portion of Argonaute and consists of two subdomains, one of which provides the ...

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000001.11 Reference GRCh38.p14 Primary Assembly

Range

35930718..36072500

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017000523.3 → XP_016856012.1 protein argonaute-3 isoform X1

UniProtKB/Swiss-Prot

B1ALI0, Q5TA55, Q9H1U6, Q9H9G7

UniProtKB/TrEMBL

A8KA05

Conserved Domains (4) summary

cd02846
Location:228 → 348

PAZ_argonaute_like; PAZ domain, argonaute_like subfamily. Argonaute is part of the RNA-induced silencing complex (RISC), and is an endonuclease that plays a key role in the RNA interference pathway. The PAZ domain has been named after the proteins Piwi,Argonaut, and Zwille. ...

cd04657
Location:393 → 818

Piwi_ago-like; PIWI domain, Argonaute-like subfamily. Argonaute is the central component of the RNA-induced silencing complex (RISC) and related complexes. The PIWI domain is the C-terminal portion of Argonaute and consists of two subdomains, one of which provides the ...

pfam08699
Location:177 → 227

ArgoL1; Argonaute linker 1 domain

pfam16486
Location:73 → 167

ArgoN; N-terminal domain of argonaute
XM_005270575.5 → XP_005270632.1 protein argonaute-3 isoform X1

See identical proteins and their annotated locations for XP_005270632.1

UniProtKB/Swiss-Prot

B1ALI0, Q5TA55, Q9H1U6, Q9H9G7

UniProtKB/TrEMBL

A8KA05

Conserved Domains (4) summary

cd02846
Location:228 → 348

PAZ_argonaute_like; PAZ domain, argonaute_like subfamily. Argonaute is part of the RNA-induced silencing complex (RISC), and is an endonuclease that plays a key role in the RNA interference pathway. The PAZ domain has been named after the proteins Piwi,Argonaut, and Zwille. ...

cd04657
Location:393 → 818

Piwi_ago-like; PIWI domain, Argonaute-like subfamily. Argonaute is the central component of the RNA-induced silencing complex (RISC) and related complexes. The PIWI domain is the C-terminal portion of Argonaute and consists of two subdomains, one of which provides the ...

pfam08699
Location:177 → 227

ArgoL1; Argonaute linker 1 domain

pfam16486
Location:73 → 167

ArgoN; N-terminal domain of argonaute
XM_011540879.4 → XP_011539181.1 protein argonaute-3 isoform X2

See identical proteins and their annotated locations for XP_011539181.1

UniProtKB/TrEMBL

A8KA05

Conserved Domains (4) summary

cd02846
Location:213 → 333

PAZ_argonaute_like; PAZ domain, argonaute_like subfamily. Argonaute is part of the RNA-induced silencing complex (RISC), and is an endonuclease that plays a key role in the RNA interference pathway. The PAZ domain has been named after the proteins Piwi,Argonaut, and Zwille. ...

cd04657
Location:378 → 803

Piwi_ago-like; PIWI domain, Argonaute-like subfamily. Argonaute is the central component of the RNA-induced silencing complex (RISC) and related complexes. The PIWI domain is the C-terminal portion of Argonaute and consists of two subdomains, one of which provides the ...

pfam08699
Location:162 → 212

ArgoL1; Argonaute linker 1 domain

pfam16486
Location:58 → 152

ArgoN; N-terminal domain of argonaute
XM_017000526.3 → XP_016856015.1 protein argonaute-3 isoform X3

UniProtKB/TrEMBL

B4E1P5

Conserved Domains (2) summary

cd02846
Location:1 → 114

PAZ_argonaute_like; PAZ domain, argonaute_like subfamily. Argonaute is part of the RNA-induced silencing complex (RISC), and is an endonuclease that plays a key role in the RNA interference pathway. The PAZ domain has been named after the proteins Piwi,Argonaut, and Zwille. ...

cd04657
Location:159 → 584

Piwi_ago-like; PIWI domain, Argonaute-like subfamily. Argonaute is the central component of the RNA-induced silencing complex (RISC) and related complexes. The PIWI domain is the C-terminal portion of Argonaute and consists of two subdomains, one of which provides the ...
XM_017000524.3 → XP_016856013.1 protein argonaute-3 isoform X3

UniProtKB/TrEMBL

B4E1P5

Conserved Domains (2) summary

cd02846
Location:1 → 114

PAZ_argonaute_like; PAZ domain, argonaute_like subfamily. Argonaute is part of the RNA-induced silencing complex (RISC), and is an endonuclease that plays a key role in the RNA interference pathway. The PAZ domain has been named after the proteins Piwi,Argonaut, and Zwille. ...

cd04657
Location:159 → 584

Piwi_ago-like; PIWI domain, Argonaute-like subfamily. Argonaute is the central component of the RNA-induced silencing complex (RISC) and related complexes. The PIWI domain is the C-terminal portion of Argonaute and consists of two subdomains, one of which provides the ...
XM_047448134.1 → XP_047304090.1 protein argonaute-3 isoform X3
XM_005270576.5 → XP_005270633.1 protein argonaute-3 isoform X4

UniProtKB/TrEMBL

B4E1P5

Conserved Domains (2) summary

cd02846
Location:1 → 73

PAZ_argonaute_like; PAZ domain, argonaute_like subfamily. Argonaute is part of the RNA-induced silencing complex (RISC), and is an endonuclease that plays a key role in the RNA interference pathway. The PAZ domain has been named after the proteins Piwi,Argonaut, and Zwille. ...

cd04657
Location:118 → 543

Piwi_ago-like; PIWI domain, Argonaute-like subfamily. Argonaute is the central component of the RNA-induced silencing complex (RISC) and related complexes. The PIWI domain is the C-terminal portion of Argonaute and consists of two subdomains, one of which provides the ...