AGO4 argonaute RISC component 4 [Homo sapiens (human)] - Gene

Summary

Official Symbol: AGO4provided by HGNC
Official Full Name: argonaute RISC component 4provided by HGNC
Primary source: HGNC:HGNC:18424
See related: Ensembl:ENSG00000134698 MIM:607356; AllianceGenome:HGNC:18424
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: EIF2C4
Summary: This gene encodes a member of the Argonaute family of proteins which contain PAZ and PIWI domains and play an integral role in RNA interference and short-interfering-RNA-mediated gene silencing. This gene is located on chromosome 1 in a cluster of related family members. [provided by RefSeq, Mar 2017]
Expression: Ubiquitous expression in skin (RPKM 10.1), bone marrow (RPKM 8.1) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 1p34.3

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	1	NC_000001.11 (35807636..35857890)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	1	NC_060925.1 (35670525..35720783)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	1	NC_000001.10 (36273237..36323491)

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: Tissue-specific circular RNA induction during human fetal development
Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
BioProject: PRJNA270632
Publication: PMID 26076956
Analysis date: Mon Apr 2 22:54:59 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

AGO4 suppresses tumor growth by modulating autophagy and apoptosis via enhancing TRIM21-mediated ubiquitination of GRP78 in a p53-independent manner.
Title: AGO4 suppresses tumor growth by modulating autophagy and apoptosis via enhancing TRIM21-mediated ubiquitination of GRP78 in a p53-independent manner.
The Importance of AGO 1 and 4 in Post-Transcriptional Gene Regulatory Function of tRF5-GluCTC, an Respiratory Syncytial Virus-Induced tRNA-Derived RNA Fragment.
Title: The Importance of AGO 1 and 4 in Post-Transcriptional Gene Regulatory Function of tRF5-GluCTC, an Respiratory Syncytial Virus-Induced tRNA-Derived RNA Fragment.
Chimeras with Ago4 N-terminal domains were defective in RISC activation & sometimes also in RNA loading. This highlights the pleiotropic role of the Ago N domain & emphasizes the unique position of human Ago4 within the Ago protein family.
Title: Molecular dissection of human Argonaute proteins by DNA shuffling.
EIF2C2-4 and PIWIL4 appear increased in advanced tumors with distant metastasis, suggesting they may promote tumor invasion
Title: Argonaute proteins: potential biomarkers for human colon cancer.
EIF2C4 protein is expressed in differentiating and terminally differentiated N-type cells more than in S- and I-type cells
Title: Differential expression of Dicer and Argonaute genes during the differentiation of human neuroblastoma cells.
The specificity of RNA interference depends on the concentration of Ago1, Ago3, and Ago4 relative to Ago2.
Title: Importance of translation and nonnucleolytic ago proteins for on-target RNA interference.

Submit: New GeneRIF Correction

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

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated 2024-10-08) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated 2024-10-08) ClinGen Genome Curation Page

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-74548 (e-PCR)
- UniSTS:12802

D11S2560 (e-PCR)
- UniSTS:37928

AL010009 (e-PCR)
- UniSTS:72273

A009K46 (e-PCR)
- UniSTS:29384

RH80595 (e-PCR)
- UniSTS:92630

G32631 (e-PCR)
- UniSTS:117214

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables RNA endonuclease activity	IBA Inferred from Biological aspect of Ancestor more info
enables double-stranded RNA binding	IDA Inferred from Direct Assay more info	PubMed
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 male gonad development	IEA Inferred from Electronic Annotation more info
involved_in male meiotic nuclear division	IEA Inferred from Electronic Annotation more info
involved_in miRNA metabolic process	IEA Inferred from Electronic Annotation more info
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 negative regulation of apoptotic process	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 cell morphogenesis	IEA Inferred from Electronic Annotation more info
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
involved_in synaptonemal complex assembly	IEA Inferred from Electronic Annotation more info

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
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
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: protein argonaute-4

Names: argonaute 4, RISC catalytic component; argonaute RISC catalytic component 4; eukaryotic translation initiation factor 2C, 4

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_017629.4 → NP_060099.2 protein argonaute-4

See identical proteins and their annotated locations for NP_060099.2

Status: REVIEWED

Source sequence(s)

AB046787, AL354864, AL359186, CA419947

Consensus CDS

CCDS397.1

UniProtKB/Swiss-Prot

A7MD27, Q9HCK5

Related

ENSP00000362306.3, ENST00000373210.4

Conserved Domains (4) summary

cd02846
Location:217 → 337

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:384 → 819

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:166 → 216

ArgoL1; Argonaute linker 1 domain

pfam16486
Location:26 → 155

ArgoN; N-terminal domain of argonaute

RNA

NR_146062.2 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs at both the 5' and 3' ends compared to variant 1. This variant is represented as non-coding because translation of the expected ORF would render the transcript a candidate for nonsense-mediated decay (NMD).

Source sequence(s)

AL354864, AL359186

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

35807636..35857890

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_005270578.4 → XP_005270635.1 protein argonaute-4 isoform X1

See identical proteins and their annotated locations for XP_005270635.1

Conserved Domains (4) summary

cd02846
Location:150 → 270

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:317 → 752

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:99 → 149

ArgoL1; Argonaute linker 1 domain

pfam16486
Location:4 → 88

ArgoN; N-terminal domain of argonaute
XM_047448151.1 → XP_047304107.1 protein argonaute-4 isoform X4
XM_047448156.1 → XP_047304112.1 protein argonaute-4 isoform X5
XM_005270579.4 → XP_005270636.1 protein argonaute-4 isoform X1

See identical proteins and their annotated locations for XP_005270636.1

Conserved Domains (4) summary

cd02846
Location:150 → 270

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:317 → 752

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:99 → 149

ArgoL1; Argonaute linker 1 domain

pfam16486
Location:4 → 88

ArgoN; N-terminal domain of argonaute
XM_011540883.3 → XP_011539185.1 protein argonaute-4 isoform X2

Conserved Domains (3) summary

cd02846
Location:67 → 187

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:234 → 669

Piwi_ago-like; 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 ...

pfam08699
Location:17 → 66

ArgoL1; Argonaute linker 1 domain
XM_011540884.3 → XP_011539186.1 protein argonaute-4 isoform X3

Conserved Domains (2) summary

cd02846
Location:16 → 136

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:183 → 618

Piwi_ago-like; 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 ...