AGO1

Protein identityUniProt · HPA

UniProt accession

Q9UL18

Gene

AGO1

Ensembl

ENSG00000092847

Chromosome

1

Canonical length

857 aa

Protein class

Predicted intracellular proteins

Subcellular location

Cytosol,Cytoplasmic bodies

OverviewNCBI Gene

This gene encodes a member of the argonaute family of proteins, which associate with small RNAs and have important roles in RNA interference (RNAi) and RNA silencing. This protein binds to microRNAs (miRNAs) or small interfering RNAs (siRNAs) and represses translation of mRNAs that are complementary to them. It is also involved in transcriptional gene silencing (TGS) of promoter regions that are complementary to bound short antigene RNAs (agRNAs), as well as in the degradation of miRNA-bound mRNA targets. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. A recent study showed this gene to be an authentic stop codon readthrough target, and that its mRNA could give rise to an additional C-terminally extended isoform by use of an alternative in-frame translation termination codon. [provided by RefSeq, Nov 2015]

Canonical amino-acid sequenceUniProt

857 residues, UniProt reviewed canonical sequence.

>Q9UL18|AGO1
     1  MEAGPSGAAA GAYLPPLQQV FQAPRRPGIG TVGKPIKLLA NYFEVDIPKI DVYHYEVDIK
    61  PDKCPRRVNR EVVEYMVQHF KPQIFGDRKP VYDGKKNIYT VTALPIGNER VDFEVTIPGE
   121  GKDRIFKVSI KWLAIVSWRM LHEALVSGQI PVPLESVQAL DVAMRHLASM RYTPVGRSFF
   181  SPPEGYYHPL GGGREVWFGF HQSVRPAMWK MMLNIDVSAT AFYKAQPVIE FMCEVLDIRN
   241  IDEQPKPLTD SQRVRFTKEI KGLKVEVTHC GQMKRKYRVC NVTRRPASHQ TFPLQLESGQ
   301  TVECTVAQYF KQKYNLQLKY PHLPCLQVGQ EQKHTYLPLE VCNIVAGQRC IKKLTDNQTS
   361  TMIKATARSA PDRQEEISRL MKNASYNLDP YIQEFGIKVK DDMTEVTGRV LPAPILQYGG
   421  RNRAIATPNQ GVWDMRGKQF YNGIEIKVWA IACFAPQKQC REEVLKNFTD QLRKISKDAG
   481  MPIQGQPCFC KYAQGADSVE PMFRHLKNTY SGLQLIIVIL PGKTPVYAEV KRVGDTLLGM
   541  ATQCVQVKNV VKTSPQTLSN LCLKINVKLG GINNILVPHQ RSAVFQQPVI FLGADVTHPP
   601  AGDGKKPSIT AVVGSMDAHP SRYCATVRVQ RPRQEIIEDL SYMVRELLIQ FYKSTRFKPT
   661  RIIFYRDGVP EGQLPQILHY ELLAIRDACI KLEKDYQPGI TYIVVQKRHH TRLFCADKNE
   721  RIGKSGNIPA GTTVDTNITH PFEFDFYLCS HAGIQGTSRP SHYYVLWDDN RFTADELQIL
   781  TYQLCHTYVR CTRSVSIPAP AYYARLVAFR ARYHLVDKEH DSGEGSHISG QSNGRDPQAL
   841  AKAVQVHQDT LRTMYFA

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against AGO1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.25

Highest tissue expression

7.9 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about AGO1.

Disease | AllUniProt

Conditions AGO1 is implicated in, by any mechanism.

• Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures (NEDLBAS) MIM:620292

Disease | GeneticClinVar

16 pathogenic / likely-pathogenic of 190 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Neurodevelopmental disorder with language delay and behavioral abnormalities, with or without seizures
• Intellectual disability
• Inborn genetic diseases
• AGO1-associated disorder
• Neurodevelopmental abnormality

ReferencesPubMed · IEDB

Publications for AGO1 from three distinct lines of evidence, kept separate because they answer different questions: whether antibodies are directed at the protein, whether a B-cell epitope has been mapped on it, and whether a T-cell epitope has. Each is labelled with its source.

Sources: PubMed — antigen-level antibody evidence from a custom retrieval. Records matching a controlled set of autoantibody terms (the MeSH descriptors Autoantibodies and Autoantigens, with title and abstract term variants) were obtained through NCBI E-utilities, and their titles and abstracts parsed for constructions that direct an antibody at a named protein rather than for co-occurrence. Captured names were resolved against UniProt nomenclature and each antigen adjudicated individually against the source text. Bibliographic records from PubMed and MeSH, U.S. National Library of Medicine; citation metrics from NIH iCite (Hutchins et al., PLoS Biology 2016). Titles link to PubMed; abstracts are not reproduced here. The NLM does not endorse this analysis.

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.06

gnomAD pLI

1

gnomAD missense Z

5.68

DepMap mean gene effect

-0.13

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• miRNA metabolic process
• miRNA processing
• miRNA-mediated gene silencing by inhibition of translation
• negative regulation of angiogenesis
• nuclear-transcribed mRNA catabolic process
• positive regulation of gene expression
• positive regulation of non-canonical NF-kappaB signal transduction
• positive regulation of transcription by RNA polymerase II
• pre-miRNA processing
• regulation of mRNA stability
• regulatory ncRNA-mediated post-transcriptional gene silencing
• RISC complex assembly

Molecular functions

• core promoter sequence-specific DNA binding
• double-stranded RNA binding
• miRNA binding
• RNA binding
• RNA polymerase II cis-regulatory region sequence-specific DNA binding
• RNA polymerase II complex binding
• single-stranded RNA binding

Cellular components

• cytoplasm
• cytoplasmic ribonucleoprotein granule
• cytosol
• nucleoplasm
• nucleus
• P-body
• RISC complex
• RISC-loading complex

Protein domainsUniProt · Pfam · InterPro

• PAZ domain
• Piwi domain
• Ribonuclease H-like superfamily
• Argonaute, linker 1 domain
• Argonaute linker 2 domain
• Protein argonaute, Mid domain
• Protein argonaute, N-terminal
• PAZ domain superfamily
• Ribonuclease H superfamily
• Argonaute-like, PIWI domain
• PAZ domain
• Piwi domain
• Argonaute linker 1 domain
• N-terminal domain of argonaute
• Mid domain of argonaute
• Argonaute linker 2 domain

KeywordsUniProt

• Cytoplasm
• Epilepsy
• Intellectual disability
• Repressor
• Ribonucleoprotein
• RNA-binding
• RNA-mediated gene silencing
• Transcription
• Transcription regulation
• Translation regulation
• Ubl conjugation

InteractionsUniProt · HPA

Protein binding partners of AGO1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• AGO2
• AJUBA
• APOBEC3F
• APOBEC3G
• APOBEC3H
• DDB1
• DDX47
• DDX5
• DDX6
• DHX30
• DHX36
• DICER1
• ELAVL1
• HNRNPF
• IGF2BP1
• ILF3
• IMP8
• LIMD1
• MATR3
• MOV10
• PABPC1
• PRMT5
• RBM4
• SART3
• TNRC6B
• UPF1
• WTIP
• YBX1
• TNRC6A
• AIP
• FKBP5
• IPO8
• PPP5C
• TNRC6C