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Protein

Protein argonaute-1

Gene

AGO1

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) or short interfering RNAs (siRNAs), and represses the translation of mRNAs which are complementary to them. Lacks endonuclease activity and does not appear to cleave target mRNAs. Also required for transcriptional gene silencing (TGS) of promoter regions which are complementary to bound short antigene RNAs (agRNAs).3 Publications

Miscellaneous

Lacks RNA cleavage activity due to the absence of the conserved His at position 805, but also because it binds the RNA in a subtly different manner that precludes efficient cleavage.

GO - Molecular functioni

  • core promoter binding Source: BHF-UCL
  • double-stranded RNA binding Source: BHF-UCL
  • miRNA binding Source: BHF-UCL
  • RNA binding Source: UniProtKB
  • RNA polymerase II core binding Source: BHF-UCL
  • RNA polymerase II proximal promoter sequence-specific DNA binding Source: Ensembl
  • 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
  • miRNA metabolic process Source: Ensembl
  • negative regulation of angiogenesis Source: BHF-UCL
  • nuclear-transcribed mRNA catabolic process Source: UniProtKB
  • positive regulation of NIK/NF-kappaB signaling Source: Ensembl
  • positive regulation of transcription by RNA polymerase II Source: BHF-UCL
  • 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 gene silencing by miRNA Source: Reactome
  • regulation of megakaryocyte differentiation Source: Reactome
  • RNA secondary structure unwinding Source: BHF-UCL
  • transcription, DNA-templated Source: UniProtKB-KW
  • Wnt signaling pathway, calcium modulating pathway Source: Reactome

Keywordsi

Molecular functionRepressor, Ribonucleoprotein, RNA-binding
Biological processRNA-mediated gene silencing, Transcription, Transcription regulation, Translation regulation

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-5578749 Transcriptional regulation 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-1
Short name:
Argonaute1
Short name:
hAgo1
Alternative name(s):
Argonaute RISC catalytic component 1
Eukaryotic translation initiation factor 2C 1
Short name:
eIF-2C 1
Short name:
eIF2C 1
Putative RNA-binding protein Q99
Gene namesi
Name:AGO1
Synonyms:EIF2C1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000092847.11
HGNCiHGNC:3262 AGO1
MIMi606228 gene
neXtProtiNX_Q9UL18

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
Mutagenesisi670P → S: Confers modest RNA cleavage activity; when associated with Q-675 and H-805. 1 Publication1
Mutagenesisi674L → F: Confers modest RNA cleavage activity; when associated with H-805. 1 Publication1
Mutagenesisi675P → Q: Does not confer enzyme activity by itself. Confers low RNA cleavage activity; when associated with H-805. Confers modest RNA cleavage activity; when associated with S-670 and H-805. 1 Publication1
Mutagenesisi805R → H: Does not confer enzyme activity by itself. Confers modest RNA cleavage activity; when associated with F-674. 2 Publications1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi26523
OpenTargetsiENSG00000092847
PharmGKBiPA27693

Polymorphism and mutation databases

BioMutaiAGO1
DMDMi88984241

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001940551 – 857Protein argonaute-1Add BLAST857

Proteomic databases

EPDiQ9UL18
MaxQBiQ9UL18
PaxDbiQ9UL18
PeptideAtlasiQ9UL18
PRIDEiQ9UL18

PTM databases

iPTMnetiQ9UL18
PhosphoSitePlusiQ9UL18

Expressioni

Gene expression databases

BgeeiENSG00000092847
CleanExiHS_EIF2C1
ExpressionAtlasiQ9UL18 baseline and differential
GenevisibleiQ9UL18 HS

Interactioni

Subunit structurei

Interacts with DDB1, DDX5, DDX6, DHX30, DHX36, DDX47, DICER1, AGO2, ELAVL1, HNRNPF, IGF2BP1, ILF3, IMP8, MATR3, MOV10, PABPC1, PRMT5, RBM4, SART3, TNRC6B, UPF1 and YBX1. Associates with polysomes and messenger ribonucleoproteins (mNRPs). Interacts with LIMD1, WTIP and AJUBA. Interacts with APOBEC3F, APOBEC3G and APOBEC3H.8 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • RNA polymerase II core binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi117726, 56 interactors
DIPiDIP-29193N
IntActiQ9UL18, 185 interactors
MINTiQ9UL18
STRINGi9606.ENSP00000362300

Structurei

Secondary structure

1857
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi33 – 46Combined sources14
Beta strandi51 – 62Combined sources12
Helixi66 – 79Combined sources14
Helixi81 – 85Combined sources5
Beta strandi94 – 102Combined sources9
Turni105 – 108Combined sources4
Beta strandi110 – 115Combined sources6
Beta strandi125 – 137Combined sources13
Helixi138 – 147Combined sources10
Helixi154 – 171Combined sources18
Beta strandi172 – 175Combined sources4
Beta strandi178 – 180Combined sources3
Beta strandi189 – 191Combined sources3
Beta strandi194 – 206Combined sources13
Beta strandi208 – 223Combined sources16
Helixi228 – 236Combined sources9
Turni241 – 243Combined sources3
Helixi250 – 260Combined sources11
Beta strandi264 – 268Combined sources5
Turni269 – 272Combined sources4
Beta strandi276 – 286Combined sources11
Turni287 – 289Combined sources3
Beta strandi291 – 295Combined sources5
Beta strandi301 – 305Combined sources5
Helixi306 – 314Combined sources9
Beta strandi323 – 328Combined sources6
Helixi331 – 333Combined sources3
Beta strandi335 – 338Combined sources4
Helixi339 – 341Combined sources3
Beta strandi342 – 344Combined sources3
Helixi356 – 366Combined sources11
Helixi370 – 384Combined sources15
Helixi386 – 388Combined sources3
Helixi390 – 394Combined sources5
Beta strandi404 – 410Combined sources7
Turni420 – 423Combined sources4
Beta strandi448 – 453Combined sources6
Turni457 – 459Combined sources3
Helixi462 – 478Combined sources17
Beta strandi488 – 492Combined sources5
Helixi496 – 498Combined sources3
Helixi499 – 509Combined sources11
Beta strandi515 – 520Combined sources6
Helixi526 – 535Combined sources10
Turni536 – 538Combined sources3
Beta strandi542 – 546Combined sources5
Helixi547 – 551Combined sources5
Helixi555 – 568Combined sources14
Helixi578 – 580Combined sources3
Helixi583 – 586Combined sources4
Beta strandi589 – 597Combined sources9
Beta strandi608 – 615Combined sources8
Beta strandi617 – 620Combined sources4
Beta strandi623 – 631Combined sources9
Helixi640 – 655Combined sources16
Beta strandi660 – 666Combined sources7
Helixi671 – 673Combined sources3
Helixi674 – 692Combined sources19
Beta strandi699 – 706Combined sources8
Beta strandi713 – 717Combined sources5
Helixi718 – 720Combined sources3
Turni723 – 726Combined sources4
Beta strandi732 – 734Combined sources3
Beta strandi736 – 739Combined sources4
Beta strandi741 – 743Combined sources3
Beta strandi745 – 749Combined sources5
Beta strandi755 – 757Combined sources3
Beta strandi761 – 768Combined sources8
Helixi774 – 784Combined sources11
Beta strandi791 – 793Combined sources3
Helixi799 – 814Combined sources16
Helixi837 – 843Combined sources7
Helixi848 – 851Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1SI2X-ray2.60A225-369[»]
1SI3X-ray2.60A225-369[»]
4KREX-ray1.75A1-857[»]
4KRFX-ray2.10A1-857[»]
4KXTX-ray2.29A1-857[»]
5W6VX-ray2.83A1-857[»]
ProteinModelPortaliQ9UL18
SMRiQ9UL18
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9UL18

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini226 – 346PAZPROSITE-ProRule annotationAdd BLAST121
Domaini515 – 816PiwiPROSITE-ProRule annotationAdd BLAST302

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni309 – 314Interaction with guide RNA6
Regioni522 – 564Interaction with guide RNAAdd BLAST43
Regioni670 – 675Impairs access of bound RNA to the active site6
Regioni708 – 712Interaction with guide RNA5
Regioni751 – 759Interaction with guide RNA9
Regioni788 – 813Interaction with guide RNAAdd BLAST26

Sequence similaritiesi

Belongs to the argonaute family. Ago subfamily.Curated

Phylogenomic databases

eggNOGiKOG1041 Eukaryota
ENOG410XP07 LUCA
GeneTreeiENSGT00760000119148
HOGENOMiHOG000116043
InParanoidiQ9UL18
KOiK11593
OMAiTNPNNIE
OrthoDBiEOG091G020J
PhylomeDBiQ9UL18
TreeFamiTF101510

Family and domain databases

Gene3Di3.30.420.10, 1 hit
InterProiView protein in InterPro
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

Sequencei

Sequence statusi: Complete.

Q9UL18-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEAGPSGAAA GAYLPPLQQV FQAPRRPGIG TVGKPIKLLA NYFEVDIPKI
60 70 80 90 100
DVYHYEVDIK PDKCPRRVNR EVVEYMVQHF KPQIFGDRKP VYDGKKNIYT
110 120 130 140 150
VTALPIGNER VDFEVTIPGE GKDRIFKVSI KWLAIVSWRM LHEALVSGQI
160 170 180 190 200
PVPLESVQAL DVAMRHLASM RYTPVGRSFF SPPEGYYHPL GGGREVWFGF
210 220 230 240 250
HQSVRPAMWK MMLNIDVSAT AFYKAQPVIE FMCEVLDIRN IDEQPKPLTD
260 270 280 290 300
SQRVRFTKEI KGLKVEVTHC GQMKRKYRVC NVTRRPASHQ TFPLQLESGQ
310 320 330 340 350
TVECTVAQYF KQKYNLQLKY PHLPCLQVGQ EQKHTYLPLE VCNIVAGQRC
360 370 380 390 400
IKKLTDNQTS TMIKATARSA PDRQEEISRL MKNASYNLDP YIQEFGIKVK
410 420 430 440 450
DDMTEVTGRV LPAPILQYGG RNRAIATPNQ GVWDMRGKQF YNGIEIKVWA
460 470 480 490 500
IACFAPQKQC REEVLKNFTD QLRKISKDAG MPIQGQPCFC KYAQGADSVE
510 520 530 540 550
PMFRHLKNTY SGLQLIIVIL PGKTPVYAEV KRVGDTLLGM ATQCVQVKNV
560 570 580 590 600
VKTSPQTLSN LCLKINVKLG GINNILVPHQ RSAVFQQPVI FLGADVTHPP
610 620 630 640 650
AGDGKKPSIT AVVGSMDAHP SRYCATVRVQ RPRQEIIEDL SYMVRELLIQ
660 670 680 690 700
FYKSTRFKPT RIIFYRDGVP EGQLPQILHY ELLAIRDACI KLEKDYQPGI
710 720 730 740 750
TYIVVQKRHH TRLFCADKNE RIGKSGNIPA GTTVDTNITH PFEFDFYLCS
760 770 780 790 800
HAGIQGTSRP SHYYVLWDDN RFTADELQIL TYQLCHTYVR CTRSVSIPAP
810 820 830 840 850
AYYARLVAFR ARYHLVDKEH DSGEGSHISG QSNGRDPQAL AKAVQVHQDT

LRTMYFA
Length:857
Mass (Da):97,214
Last modified:February 21, 2006 - v3
Checksum:i1DBB524AE7CBAF66
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti242D → N in AAH63275 (PubMed:15489334).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_078651199G → S Probable disease-associated mutation found in a patient with moderate intellectual disability and epilepsy. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF093097 mRNA Translation: AAF00068.1
AL139286 Genomic DNA No translation available.
BC063275 mRNA Translation: AAH63275.1
CCDSiCCDS398.1
RefSeqiNP_001304051.1, NM_001317122.1
NP_001304052.1, NM_001317123.1
NP_036331.1, NM_012199.4
UniGeneiHs.22867
Hs.656677

Genome annotation databases

EnsembliENST00000373204; ENSP00000362300; ENSG00000092847
GeneIDi26523
KEGGihsa:26523
UCSCiuc001bzl.4 human

Similar proteinsi

Entry informationi

Entry nameiAGO1_HUMAN
AccessioniPrimary (citable) accession number: Q9UL18
Secondary accession number(s): Q5TA57, Q6P4S0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: February 21, 2006
Last modified: May 23, 2018
This is version 157 of the entry and version 3 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. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. Translation initiation factors
    List of translation initiation factor entries
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families

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