ID   AGO1_HUMAN              Reviewed;         857 AA.
AC   Q9UL18; Q5TA57; Q6P4S0;
DT   01-DEC-2000, integrated into UniProtKB/Swiss-Prot.
DT   21-FEB-2006, sequence version 3.
DT   27-MAR-2024, entry version 192.
DE   RecName: Full=Protein argonaute-1;
DE            Short=Argonaute1;
DE            Short=hAgo1;
DE   AltName: Full=Argonaute RISC catalytic component 1;
DE   AltName: Full=Eukaryotic translation initiation factor 2C 1;
DE            Short=eIF-2C 1;
DE            Short=eIF2C 1;
DE   AltName: Full=Putative RNA-binding protein Q99;
GN   Name=AGO1; Synonyms=EIF2C1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=10534406; DOI=10.1006/geno.1999.5951;
RA   Koesters R., Adams V., Betts D., Moos R., Schmid M., Siermann A.,
RA   Hassam S., Weitz S., Lichter P., Heitz P.U., von Knebel Doeberitz M.,
RA   Briner J.;
RT   "Human eukaryotic initiation factor EIF2C1 gene: cDNA sequence, genomic
RT   organization, localization to chromosomal bands 1p34-p35, and expression.";
RL   Genomics 61:210-218(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16710414; DOI=10.1038/nature04727;
RA   Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA   Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA   Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA   Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA   Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA   Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA   Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA   Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA   Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA   Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA   Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA   Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA   Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA   Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA   Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA   Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA   Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA   Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA   McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA   Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA   Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA   Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA   Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA   Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA   White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA   Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA   Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA   Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT   "The DNA sequence and biological annotation of human chromosome 1.";
RL   Nature 441:315-321(2006).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Placenta;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   ASSOCIATION WITH MIRNA.
RX   PubMed=15260970; DOI=10.1016/j.molcel.2004.07.007;
RA   Meister G., Landthaler M., Patkaniowska A., Dorsett Y., Teng G., Tuschl T.;
RT   "Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs.";
RL   Mol. Cell 15:185-197(2004).
RN   [5]
RP   FUNCTION, INTERACTION WITH DICER1; MOV10; PRMT5 AND TNRC6B, AND SUBCELLULAR
RP   LOCATION.
RX   PubMed=16289642; DOI=10.1016/j.cub.2005.10.048;
RA   Meister G., Landthaler M., Peters L., Chen P.Y., Urlaub H., Luehrmann R.,
RA   Tuschl T.;
RT   "Identification of novel argonaute-associated proteins.";
RL   Curr. Biol. 15:2149-2155(2005).
RN   [6]
RP   FUNCTION.
RX   PubMed=16936728; DOI=10.1038/nsmb1140;
RA   Janowski B.A., Huffman K.E., Schwartz J.C., Ram R., Nordsell R.,
RA   Shames D.S., Minna J.D., Corey D.R.;
RT   "Involvement of AGO1 and AGO2 in mammalian transcriptional silencing.";
RL   Nat. Struct. Mol. Biol. 13:787-792(2006).
RN   [7]
RP   INTERACTION WITH DDX6 AND AGO2.
RX   PubMed=16756390; DOI=10.1371/journal.pbio.0040210;
RA   Chu C.-Y., Rana T.M.;
RT   "Translation repression in human cells by microRNA-induced gene silencing
RT   requires RCK/p54.";
RL   PLoS Biol. 4:E210-E210(2006).
RN   [8]
RP   ASSOCIATION WITH POLYSOMES AND MNRP, AND INTERACTION WITH DDB1; DDX5;
RP   DHX30; DHX36; DDX47; ELAVL1; HNRNPF; IGF2BP1; ILF3; MATR3; PABPC1; RBM4;
RP   SART3; UPF1 AND YBX1.
RX   PubMed=17932509; DOI=10.1038/sj.embor.7401088;
RA   Hoeck J., Weinmann L., Ender C., Ruedel S., Kremmer E., Raabe M.,
RA   Urlaub H., Meister G.;
RT   "Proteomic and functional analysis of Argonaute-containing mRNA-protein
RT   complexes in human cells.";
RL   EMBO Rep. 8:1052-1060(2007).
RN   [9]
RP   FUNCTION.
RX   PubMed=18771919; DOI=10.1016/j.cub.2008.07.072;
RA   Wu L., Fan J., Belasco J.G.;
RT   "Importance of translation and nonnucleolytic ago proteins for on-target
RT   RNA interference.";
RL   Curr. Biol. 18:1327-1332(2008).
RN   [10]
RP   INTERACTION WITH IMP8.
RX   PubMed=19167051; DOI=10.1016/j.cell.2008.12.023;
RA   Weinmann L., Hoeck J., Ivacevic T., Ohrt T., Muetze J., Schwille P.,
RA   Kremmer E., Benes V., Urlaub H., Meister G.;
RT   "Importin 8 is a gene silencing factor that targets argonaute proteins to
RT   distinct mRNAs.";
RL   Cell 136:496-507(2009).
RN   [11]
RP   SUBCELLULAR LOCATION, AND INTERACTION WITH LIMD1; WTIP AND AJUBA.
RX   PubMed=20616046; DOI=10.1073/pnas.0914987107;
RA   James V., Zhang Y., Foxler D.E., de Moor C.H., Kong Y.W., Webb T.M.,
RA   Self T.J., Feng Y., Lagos D., Chu C.Y., Rana T.M., Morley S.J.,
RA   Longmore G.D., Bushell M., Sharp T.V.;
RT   "LIM-domain proteins, LIMD1, Ajuba, and WTIP are required for microRNA-
RT   mediated gene silencing.";
RL   Proc. Natl. Acad. Sci. U.S.A. 107:12499-12504(2010).
RN   [12]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [13]
RP   INTERACTION WITH APOBEC3F; APOBEC3G AND APOBEC3H.
RX   PubMed=22915799; DOI=10.1128/jvi.00595-12;
RA   Phalora P.K., Sherer N.M., Wolinsky S.M., Swanson C.M., Malim M.H.;
RT   "HIV-1 replication and APOBEC3 antiviral activity are not regulated by P
RT   bodies.";
RL   J. Virol. 86:11712-11724(2012).
RN   [14]
RP   X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 225-369, AND RNA-BINDING.
RX   PubMed=15152257; DOI=10.1038/nature02519;
RA   Ma J.-B., Ye K., Patel D.J.;
RT   "Structural basis for overhang-specific small interfering RNA recognition
RT   by the PAZ domain.";
RL   Nature 429:318-322(2004).
RN   [15]
RP   X-RAY CRYSTALLOGRAPHY (2.29 ANGSTROMS) IN COMPLEX WITH RNA, RNA-BINDING,
RP   MUTAGENESIS OF PRO-670; PRO-675 AND ARG-805, AND LACK OF CATALYTIC
RP   ACTIVITY.
RX   PubMed=23809764; DOI=10.1016/j.celrep.2013.06.010;
RA   Nakanishi K., Ascano M., Gogakos T., Ishibe-Murakami S., Serganov A.A.,
RA   Briskin D., Morozov P., Tuschl T., Patel D.J.;
RT   "Eukaryote-specific insertion elements control human ARGONAUTE slicer
RT   activity.";
RL   Cell Rep. 3:1893-1900(2013).
RN   [16]
RP   X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) IN COMPLEX WITH RNA, LACK OF
RP   CATALYTIC ACTIVITY, AND MUTAGENESIS OF LEU-674 AND ARG-805.
RX   PubMed=23746446; DOI=10.1016/j.celrep.2013.05.033;
RA   Faehnle C.R., Elkayam E., Haase A.D., Hannon G.J., Joshua-Tor L.;
RT   "The making of a slicer: activation of human Argonaute-1.";
RL   Cell Rep. 3:1901-1909(2013).
RN   [17]
RP   VARIANT NEDLBAS PRO-190, AND INVOLVEMENT IN NEDLBAS.
RX   PubMed=23020937; DOI=10.1016/s0140-6736(12)61480-9;
RA   Rauch A., Wieczorek D., Graf E., Wieland T., Endele S., Schwarzmayr T.,
RA   Albrecht B., Bartholdi D., Beygo J., Di Donato N., Dufke A., Cremer K.,
RA   Hempel M., Horn D., Hoyer J., Joset P., Roepke A., Moog U., Riess A.,
RA   Thiel C.T., Tzschach A., Wiesener A., Wohlleber E., Zweier C., Ekici A.B.,
RA   Zink A.M., Rump A., Meisinger C., Grallert H., Sticht H., Schenck A.,
RA   Engels H., Rappold G., Schroeck E., Wieacker P., Riess O., Meitinger T.,
RA   Reis A., Strom T.M.;
RT   "Range of genetic mutations associated with severe non-syndromic sporadic
RT   intellectual disability: an exome sequencing study.";
RL   Lancet 380:1674-1682(2012).
RN   [18]
RP   VARIANT NEDLBAS SER-199, AND INVOLVEMENT IN NEDLBAS.
RX   PubMed=25356899; DOI=10.1371/journal.pgen.1004772;
RA   Hamdan F.F., Srour M., Capo-Chichi J.M., Daoud H., Nassif C., Patry L.,
RA   Massicotte C., Ambalavanan A., Spiegelman D., Diallo O., Henrion E.,
RA   Dionne-Laporte A., Fougerat A., Pshezhetsky A.V., Venkateswaran S.,
RA   Rouleau G.A., Michaud J.L.;
RT   "De novo mutations in moderate or severe intellectual disability.";
RL   PLoS Genet. 10:E1004772-E1004772(2014).
RN   [19]
RP   VARIANT NEDLBAS LYS-195.
RX   PubMed=27620904; DOI=10.1136/jmedgenet-2016-103964;
RA   Martinez F., Caro-Llopis A., Rosello M., Oltra S., Mayo S., Monfort S.,
RA   Orellana C.;
RT   "High diagnostic yield of syndromic intellectual disability by targeted
RT   next-generation sequencing.";
RL   J. Med. Genet. 54:87-92(2017).
RN   [20]
RP   VARIANT NEDLBAS SER-199.
RX   PubMed=30213762; DOI=10.1016/j.ejmg.2018.09.004;
RA   Sakaguchi A., Yamashita Y., Ishii T., Uehara T., Kosaki K., Takahashi T.,
RA   Takenouchi T.;
RT   "Further evidence of a causal association between AGO1, a critical
RT   regulator of microRNA formation, and intellectual disability/autism
RT   spectrum disorder.";
RL   Eur. J. Med. Genet. 62:103537-103537(2019).
RN   [21]
RP   VARIANTS NEDLBAS PHE-180 DEL; LEU-189; ARG-190; PRO-190; SER-199; VAL-216;
RP   HIS-253; ILE-254; LEU-324; ILE-355; ARG-358; GLU-376 DEL; PHE-418; LEU-751;
RP   MET-781 AND PHE-797.
RX   PubMed=34930816; DOI=10.1136/jmedgenet-2021-107751;
RA   Schalk A., Cousin M.A., Dsouza N.R., Challman T.D., Wain K.E., Powis Z.,
RA   Minks K., Trimouille A., Lasseaux E., Lacombe D., Angelini C., Michaud V.,
RA   Van-Gils J., Spataro N., Ruiz A., Gabau E., Stolerman E., Washington C.,
RA   Louie R., Lanpher B.C., Kemppainen J.L., Innes M., Kooy F., Meuwissen M.,
RA   Goldenberg A., Lecoquierre F., Vera G., Diderich K.E.M., Sheidley B.,
RA   El Achkar C.M., Park M., Hamdan F.F., Michaud J.L., Lewis A.J., Zweier C.,
RA   Reis A., Wagner M., Weigand H., Journel H., Keren B., Passemard S.,
RA   Mignot C., van Gassen K., Brilstra E.H., Itzikowitz G., O'Heir E.,
RA   Allen J., Donald K.A., Korf B.R., Skelton T., Thompson M., Robin N.H.,
RA   Rudy N.L., Dobyns W.B., Foss K., Zarate Y.A., Bosanko K.A., Alembik Y.,
RA   Durand B., Tran Mau-Them F., Ranza E., Blanc X., Antonarakis S.E.,
RA   McWalter K., Torti E., Millan F., Dameron A., Tokita M., Zimmermann M.T.,
RA   Klee E.W., Piton A., Gerard B.;
RT   "De novo coding variants in the AGO1 gene cause a neurodevelopmental
RT   disorder with intellectual disability.";
RL   J. Med. Genet. 59:965-975(2022).
CC   -!- FUNCTION: Required for RNA-mediated gene silencing (RNAi). Binds to
CC       short RNAs such as microRNAs (miRNAs) or short interfering RNAs
CC       (siRNAs), and represses the translation of mRNAs which are
CC       complementary to them. Lacks endonuclease activity and does not appear
CC       to cleave target mRNAs. Also required for transcriptional gene
CC       silencing (TGS) of promoter regions which are complementary to bound
CC       short antigene RNAs (agRNAs). {ECO:0000269|PubMed:16289642,
CC       ECO:0000269|PubMed:16936728, ECO:0000269|PubMed:18771919}.
CC   -!- SUBUNIT: Interacts with DDB1, DDX5, DDX6, DHX30, DHX36, DDX47, DICER1,
CC       AGO2, ELAVL1, HNRNPF, IGF2BP1, ILF3, IMP8, MATR3, MOV10, PABPC1, PRMT5,
CC       RBM4, SART3, TNRC6B, UPF1 and YBX1. Associates with polysomes and
CC       messenger ribonucleoproteins (mNRPs). Interacts with LIMD1, WTIP and
CC       AJUBA. Interacts with APOBEC3F, APOBEC3G and APOBEC3H.
CC       {ECO:0000269|PubMed:16289642, ECO:0000269|PubMed:16756390,
CC       ECO:0000269|PubMed:17932509, ECO:0000269|PubMed:19167051,
CC       ECO:0000269|PubMed:20616046, ECO:0000269|PubMed:22915799,
CC       ECO:0000269|PubMed:23746446, ECO:0000269|PubMed:23809764}.
CC   -!- INTERACTION:
CC       Q9UL18; Q9UKV8: AGO2; NbExp=3; IntAct=EBI-527363, EBI-528269;
CC       Q9UL18; Q66GS9: CEP135; NbExp=2; IntAct=EBI-527363, EBI-1046993;
CC       Q9UL18; Q9UPY3: DICER1; NbExp=5; IntAct=EBI-527363, EBI-395506;
CC       Q9UL18; P08238: HSP90AB1; NbExp=3; IntAct=EBI-527363, EBI-352572;
CC       Q9UL18; O15397: IPO8; NbExp=2; IntAct=EBI-527363, EBI-358808;
CC       Q9UL18; Q9UGP4: LIMD1; NbExp=3; IntAct=EBI-527363, EBI-2652871;
CC       Q9UL18; P53041: PPP5C; NbExp=2; IntAct=EBI-527363, EBI-716663;
CC       Q9UL18; P04156: PRNP; NbExp=2; IntAct=EBI-527363, EBI-977302;
CC       Q9UL18; Q8NDV7: TNRC6A; NbExp=5; IntAct=EBI-527363, EBI-2269715;
CC       Q9UL18; Q9UPQ9-2: TNRC6B; NbExp=4; IntAct=EBI-527363, EBI-6514011;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, P-body {ECO:0000269|PubMed:16289642,
CC       ECO:0000269|PubMed:20616046}.
CC   -!- PTM: Ubiquitinated on surface-exposed lysines by a SCF-like E3
CC       ubiquitin-protein ligase complex containing ZSWIM8 during target-
CC       directed microRNA degradation (TDMD), a process that mediates
CC       degradation of microRNAs (miRNAs). Ubiquitination by the SCF-like E3
CC       ubiquitin-protein ligase complex containing ZSWIM8 leads to its
CC       subsequent degradation, thereby exposing miRNAs for degradation. ZSWIM8
CC       recognizes and binds AGO1 when it is engaged with a TDMD target.
CC       {ECO:0000250|UniProtKB:Q9UKV8}.
CC   -!- DISEASE: Neurodevelopmental disorder with language delay and behavioral
CC       abnormalities, with or without seizures (NEDLBAS) [MIM:620292]: An
CC       autosomal dominant neurodevelopmental disorder characterized by global
CC       developmental delay with intellectual disability of varying severity,
CC       speech and motor delay, and behavioral abnormalities, including
CC       autistic features. About half of patients develop seizures.
CC       {ECO:0000269|PubMed:23020937, ECO:0000269|PubMed:25356899,
CC       ECO:0000269|PubMed:27620904, ECO:0000269|PubMed:30213762,
CC       ECO:0000269|PubMed:34930816}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- MISCELLANEOUS: Lacks RNA cleavage activity due to the absence of the
CC       conserved His at position 805, but also because it binds the RNA in a
CC       subtly different manner that precludes efficient cleavage.
CC   -!- SIMILARITY: Belongs to the argonaute family. Ago subfamily.
CC       {ECO:0000305}.
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DR   EMBL; AF093097; AAF00068.1; -; mRNA.
DR   EMBL; AL139286; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC063275; AAH63275.1; -; mRNA.
DR   CCDS; CCDS398.1; -.
DR   RefSeq; NP_001304051.1; NM_001317122.1.
DR   RefSeq; NP_001304052.1; NM_001317123.1.
DR   RefSeq; NP_036331.1; NM_012199.4.
DR   PDB; 1SI2; X-ray; 2.60 A; A=225-369.
DR   PDB; 1SI3; X-ray; 2.60 A; A=225-369.
DR   PDB; 4KRE; X-ray; 1.75 A; A=1-857.
DR   PDB; 4KRF; X-ray; 2.10 A; A=1-857.
DR   PDB; 4KXT; X-ray; 2.29 A; A=1-857.
DR   PDB; 5W6V; X-ray; 2.83 A; A=1-857.
DR   PDBsum; 1SI2; -.
DR   PDBsum; 1SI3; -.
DR   PDBsum; 4KRE; -.
DR   PDBsum; 4KRF; -.
DR   PDBsum; 4KXT; -.
DR   PDBsum; 5W6V; -.
DR   AlphaFoldDB; Q9UL18; -.
DR   SMR; Q9UL18; -.
DR   BioGRID; 117726; 168.
DR   DIP; DIP-29193N; -.
DR   IntAct; Q9UL18; 194.
DR   MINT; Q9UL18; -.
DR   STRING; 9606.ENSP00000362300; -.
DR   GlyGen; Q9UL18; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; Q9UL18; -.
DR   PhosphoSitePlus; Q9UL18; -.
DR   BioMuta; AGO1; -.
DR   DMDM; 88984241; -.
DR   EPD; Q9UL18; -.
DR   jPOST; Q9UL18; -.
DR   MassIVE; Q9UL18; -.
DR   MaxQB; Q9UL18; -.
DR   PaxDb; 9606-ENSP00000362300; -.
DR   PeptideAtlas; Q9UL18; -.
DR   ProteomicsDB; 84931; -.
DR   Pumba; Q9UL18; -.
DR   Antibodypedia; 31600; 340 antibodies from 39 providers.
DR   DNASU; 26523; -.
DR   Ensembl; ENST00000373204.6; ENSP00000362300.4; ENSG00000092847.14.
DR   GeneID; 26523; -.
DR   KEGG; hsa:26523; -.
DR   MANE-Select; ENST00000373204.6; ENSP00000362300.4; NM_012199.5; NP_036331.1.
DR   UCSC; uc001bzl.4; human.
DR   AGR; HGNC:3262; -.
DR   CTD; 26523; -.
DR   DisGeNET; 26523; -.
DR   GeneCards; AGO1; -.
DR   HGNC; HGNC:3262; AGO1.
DR   HPA; ENSG00000092847; Low tissue specificity.
DR   MalaCards; AGO1; -.
DR   MIM; 606228; gene.
DR   MIM; 620292; phenotype.
DR   neXtProt; NX_Q9UL18; -.
DR   OpenTargets; ENSG00000092847; -.
DR   Orphanet; 528084; Non-specific syndromic intellectual disability.
DR   PharmGKB; PA27693; -.
DR   VEuPathDB; HostDB:ENSG00000092847; -.
DR   eggNOG; KOG1041; Eukaryota.
DR   GeneTree; ENSGT00940000158568; -.
DR   HOGENOM; CLU_004544_4_3_1; -.
DR   InParanoid; Q9UL18; -.
DR   OMA; IHDEIFT; -.
DR   OrthoDB; 3060088at2759; -.
DR   PhylomeDB; Q9UL18; -.
DR   TreeFam; TF101510; -.
DR   PathwayCommons; Q9UL18; -.
DR   Reactome; R-HSA-1912408; Pre-NOTCH Transcription and Translation.
DR   Reactome; R-HSA-203927; MicroRNA (miRNA) biogenesis.
DR   Reactome; R-HSA-2559580; Oxidative Stress Induced Senescence.
DR   Reactome; R-HSA-2559585; Oncogene Induced Senescence.
DR   Reactome; R-HSA-4086398; Ca2+ pathway.
DR   Reactome; R-HSA-426486; Small interfering RNA (siRNA) biogenesis.
DR   Reactome; R-HSA-426496; Post-transcriptional silencing by small RNAs.
DR   Reactome; R-HSA-5578749; Transcriptional regulation by small RNAs.
DR   Reactome; R-HSA-5628897; TP53 Regulates Metabolic Genes.
DR   Reactome; R-HSA-5687128; MAPK6/MAPK4 signaling.
DR   Reactome; R-HSA-8853884; Transcriptional Regulation by VENTX.
DR   Reactome; R-HSA-8934593; Regulation of RUNX1 Expression and Activity.
DR   Reactome; R-HSA-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
DR   Reactome; R-HSA-8943723; Regulation of PTEN mRNA translation.
DR   Reactome; R-HSA-8948700; Competing endogenous RNAs (ceRNAs) regulate PTEN translation.
DR   Reactome; R-HSA-8986944; Transcriptional Regulation by MECP2.
DR   Reactome; R-HSA-9018519; Estrogen-dependent gene expression.
DR   Reactome; R-HSA-9022692; Regulation of MECP2 expression and activity.
DR   Reactome; R-HSA-9029569; NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux.
DR   Reactome; R-HSA-9759811; Regulation of CDH11 mRNA translation by microRNAs.
DR   Reactome; R-HSA-9768778; Regulation of NPAS4 mRNA translation.
DR   SignaLink; Q9UL18; -.
DR   BioGRID-ORCS; 26523; 57 hits in 1156 CRISPR screens.
DR   ChiTaRS; AGO1; human.
DR   EvolutionaryTrace; Q9UL18; -.
DR   GeneWiki; EIF2C1; -.
DR   GenomeRNAi; 26523; -.
DR   Pharos; Q9UL18; Tbio.
DR   PRO; PR:Q9UL18; -.
DR   Proteomes; UP000005640; Chromosome 1.
DR   RNAct; Q9UL18; protein.
DR   Bgee; ENSG00000092847; Expressed in ganglionic eminence and 197 other cell types or tissues.
DR   ExpressionAtlas; Q9UL18; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR   GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:HPA.
DR   GO; GO:0005829; C:cytosol; IDA:HPA.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR   GO; GO:0005634; C:nucleus; IC:BHF-UCL.
DR   GO; GO:0000932; C:P-body; IEA:UniProtKB-SubCell.
DR   GO; GO:0016442; C:RISC complex; IDA:UniProtKB.
DR   GO; GO:0070578; C:RISC-loading complex; IDA:BHF-UCL.
DR   GO; GO:0001046; F:core promoter sequence-specific DNA binding; IMP:BHF-UCL.
DR   GO; GO:0003725; F:double-stranded RNA binding; IDA:BHF-UCL.
DR   GO; GO:0035198; F:miRNA binding; IDA:BHF-UCL.
DR   GO; GO:0003723; F:RNA binding; IDA:UniProtKB.
DR   GO; GO:0000993; F:RNA polymerase II complex binding; IDA:BHF-UCL.
DR   GO; GO:0003727; F:single-stranded RNA binding; IDA:BHF-UCL.
DR   GO; GO:0035196; P:miRNA processing; IMP:BHF-UCL.
DR   GO; GO:0035278; P:miRNA-mediated gene silencing by inhibition of translation; IDA:UniProtKB.
DR   GO; GO:0016525; P:negative regulation of angiogenesis; IMP:BHF-UCL.
DR   GO; GO:0000956; P:nuclear-transcribed mRNA catabolic process; IDA:UniProtKB.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR   GO; GO:0031054; P:pre-miRNA processing; IDA:BHF-UCL.
DR   GO; GO:0070922; P:RISC complex assembly; IDA:BHF-UCL.
DR   GO; GO:0010501; P:RNA secondary structure unwinding; IDA:BHF-UCL.
DR   CDD; cd02846; PAZ_argonaute_like; 1.
DR   CDD; cd04657; Piwi_ago-like; 1.
DR   Gene3D; 3.40.50.2300; -; 1.
DR   Gene3D; 2.170.260.10; paz domain; 1.
DR   Gene3D; 3.30.420.10; Ribonuclease H-like superfamily/Ribonuclease H; 1.
DR   InterPro; IPR014811; ArgoL1.
DR   InterPro; IPR032472; ArgoL2.
DR   InterPro; IPR032473; Argonaute_Mid_dom.
DR   InterPro; IPR032474; Argonaute_N.
DR   InterPro; IPR003100; PAZ_dom.
DR   InterPro; IPR036085; PAZ_dom_sf.
DR   InterPro; IPR003165; Piwi.
DR   InterPro; IPR045246; Piwi_ago-like.
DR   InterPro; IPR012337; RNaseH-like_sf.
DR   InterPro; IPR036397; RNaseH_sf.
DR   PANTHER; PTHR22891; EUKARYOTIC TRANSLATION INITIATION FACTOR 2C; 1.
DR   PANTHER; PTHR22891:SF17; PROTEIN ARGONAUTE-1; 1.
DR   Pfam; PF08699; ArgoL1; 1.
DR   Pfam; PF16488; ArgoL2; 1.
DR   Pfam; PF16487; ArgoMid; 1.
DR   Pfam; PF16486; ArgoN; 1.
DR   Pfam; PF02170; PAZ; 1.
DR   Pfam; PF02171; Piwi; 1.
DR   SMART; SM01163; DUF1785; 1.
DR   SMART; SM00949; PAZ; 1.
DR   SMART; SM00950; Piwi; 1.
DR   SUPFAM; SSF101690; PAZ domain; 1.
DR   SUPFAM; SSF53098; Ribonuclease H-like; 1.
DR   PROSITE; PS50821; PAZ; 1.
DR   PROSITE; PS50822; PIWI; 1.
DR   Genevisible; Q9UL18; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasm; Disease variant; Epilepsy;
KW   Intellectual disability; Reference proteome; Repressor; Ribonucleoprotein;
KW   RNA-binding; RNA-mediated gene silencing; Transcription;
KW   Transcription regulation; Translation regulation; Ubl conjugation.
FT   CHAIN           1..857
FT                   /note="Protein argonaute-1"
FT                   /id="PRO_0000194055"
FT   DOMAIN          227..346
FT                   /note="PAZ"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00142"
FT   DOMAIN          515..816
FT                   /note="Piwi"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00150"
FT   REGION          309..314
FT                   /note="Interaction with guide RNA"
FT   REGION          522..564
FT                   /note="Interaction with guide RNA"
FT   REGION          670..675
FT                   /note="Impairs access of bound RNA to the active site"
FT   REGION          708..712
FT                   /note="Interaction with guide RNA"
FT   REGION          751..759
FT                   /note="Interaction with guide RNA"
FT   REGION          788..813
FT                   /note="Interaction with guide RNA"
FT   VARIANT         180
FT                   /note="Missing (in NEDLBAS)"
FT                   /evidence="ECO:0000269|PubMed:34930816"
FT                   /id="VAR_088406"
FT   VARIANT         189
FT                   /note="P -> L (in NEDLBAS)"
FT                   /evidence="ECO:0000269|PubMed:34930816"
FT                   /id="VAR_088407"
FT   VARIANT         190
FT                   /note="L -> P (in NEDLBAS)"
FT                   /evidence="ECO:0000269|PubMed:23020937,
FT                   ECO:0000269|PubMed:34930816"
FT                   /id="VAR_088408"
FT   VARIANT         190
FT                   /note="L -> R (in NEDLBAS)"
FT                   /evidence="ECO:0000269|PubMed:34930816"
FT                   /id="VAR_088409"
FT   VARIANT         195
FT                   /note="E -> K (in NEDLBAS; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:27620904"
FT                   /id="VAR_088410"
FT   VARIANT         199
FT                   /note="G -> S (in NEDLBAS)"
FT                   /evidence="ECO:0000269|PubMed:25356899,
FT                   ECO:0000269|PubMed:30213762, ECO:0000269|PubMed:34930816"
FT                   /id="VAR_078651"
FT   VARIANT         216
FT                   /note="D -> V (in NEDLBAS; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:34930816"
FT                   /id="VAR_088411"
FT   VARIANT         253
FT                   /note="R -> H (in NEDLBAS; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:34930816"
FT                   /id="VAR_088412"
FT   VARIANT         254
FT                   /note="V -> I (in NEDLBAS)"
FT                   /evidence="ECO:0000269|PubMed:34930816"
FT                   /id="VAR_088413"
FT   VARIANT         324
FT                   /note="P -> L (in NEDLBAS; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:34930816"
FT                   /id="VAR_088414"
FT   VARIANT         355
FT                   /note="T -> I (in NEDLBAS; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:34930816"
FT                   /id="VAR_088415"
FT   VARIANT         358
FT                   /note="Q -> R (in NEDLBAS; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:34930816"
FT                   /id="VAR_088416"
FT   VARIANT         376
FT                   /note="Missing (in NEDLBAS; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:34930816"
FT                   /id="VAR_088417"
FT   VARIANT         418
FT                   /note="Y -> F (in NEDLBAS; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:34930816"
FT                   /id="VAR_088418"
FT   VARIANT         751
FT                   /note="H -> L (in NEDLBAS; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:34930816"
FT                   /id="VAR_088419"
FT   VARIANT         781
FT                   /note="T -> M (in NEDLBAS; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:34930816"
FT                   /id="VAR_088420"
FT   VARIANT         797
FT                   /note="I -> F (in NEDLBAS; uncertain significance)"
FT                   /evidence="ECO:0000269|PubMed:34930816"
FT                   /id="VAR_088421"
FT   MUTAGEN         670
FT                   /note="P->S: Confers modest RNA cleavage activity; when
FT                   associated with Q-675 and H-805."
FT                   /evidence="ECO:0000269|PubMed:23809764"
FT   MUTAGEN         674
FT                   /note="L->F: Confers modest RNA cleavage activity; when
FT                   associated with H-805."
FT                   /evidence="ECO:0000269|PubMed:23746446"
FT   MUTAGEN         675
FT                   /note="P->Q: Does not confer enzyme activity by itself.
FT                   Confers low RNA cleavage activity; when associated with
FT                   H-805. Confers modest RNA cleavage activity; when
FT                   associated with S-670 and H-805."
FT                   /evidence="ECO:0000269|PubMed:23809764"
FT   MUTAGEN         805
FT                   /note="R->H: Does not confer enzyme activity by itself.
FT                   Confers modest RNA cleavage activity; when associated with
FT                   F-674."
FT                   /evidence="ECO:0000269|PubMed:23746446,
FT                   ECO:0000269|PubMed:23809764"
FT   CONFLICT        242
FT                   /note="D -> N (in Ref. 3; AAH63275)"
FT                   /evidence="ECO:0000305"
FT   STRAND          33..46
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          51..62
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           66..79
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           81..85
FT                   /evidence="ECO:0007829|PDB:4KRF"
FT   STRAND          94..102
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   TURN            105..108
FT                   /evidence="ECO:0007829|PDB:4KXT"
FT   STRAND          110..115
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          125..137
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           138..147
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           154..171
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          172..175
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          178..180
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          189..191
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          194..206
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          208..223
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           228..236
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   TURN            241..243
FT                   /evidence="ECO:0007829|PDB:1SI2"
FT   HELIX           250..260
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          264..268
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   TURN            269..272
FT                   /evidence="ECO:0007829|PDB:1SI2"
FT   STRAND          276..286
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   TURN            287..289
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          291..295
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          301..305
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           306..314
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          323..328
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           331..333
FT                   /evidence="ECO:0007829|PDB:1SI2"
FT   STRAND          335..338
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           339..341
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          342..344
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           356..366
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           370..384
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           386..388
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           390..394
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          404..410
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   TURN            420..423
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          448..453
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   TURN            457..459
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           462..478
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          488..492
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           496..498
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           499..509
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          515..520
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           526..535
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   TURN            536..538
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          542..546
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           547..551
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           555..568
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           578..580
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           583..586
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          589..597
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          608..615
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          617..620
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          623..631
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           640..655
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          660..666
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           671..673
FT                   /evidence="ECO:0007829|PDB:4KRF"
FT   HELIX           674..692
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          699..706
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          713..717
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           718..720
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   TURN            723..726
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          732..734
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          736..739
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          741..743
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          745..749
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          755..757
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          761..768
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           774..784
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   STRAND          791..793
FT                   /evidence="ECO:0007829|PDB:5W6V"
FT   HELIX           799..814
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           837..843
FT                   /evidence="ECO:0007829|PDB:4KRE"
FT   HELIX           848..851
FT                   /evidence="ECO:0007829|PDB:4KRE"
SQ   SEQUENCE   857 AA;  97214 MW;  1DBB524AE7CBAF66 CRC64;
     MEAGPSGAAA GAYLPPLQQV FQAPRRPGIG TVGKPIKLLA NYFEVDIPKI DVYHYEVDIK
     PDKCPRRVNR EVVEYMVQHF KPQIFGDRKP VYDGKKNIYT VTALPIGNER VDFEVTIPGE
     GKDRIFKVSI KWLAIVSWRM LHEALVSGQI PVPLESVQAL DVAMRHLASM RYTPVGRSFF
     SPPEGYYHPL GGGREVWFGF HQSVRPAMWK MMLNIDVSAT AFYKAQPVIE FMCEVLDIRN
     IDEQPKPLTD SQRVRFTKEI KGLKVEVTHC GQMKRKYRVC NVTRRPASHQ TFPLQLESGQ
     TVECTVAQYF KQKYNLQLKY PHLPCLQVGQ EQKHTYLPLE VCNIVAGQRC IKKLTDNQTS
     TMIKATARSA PDRQEEISRL MKNASYNLDP YIQEFGIKVK DDMTEVTGRV LPAPILQYGG
     RNRAIATPNQ GVWDMRGKQF YNGIEIKVWA IACFAPQKQC REEVLKNFTD QLRKISKDAG
     MPIQGQPCFC KYAQGADSVE PMFRHLKNTY SGLQLIIVIL PGKTPVYAEV KRVGDTLLGM
     ATQCVQVKNV VKTSPQTLSN LCLKINVKLG GINNILVPHQ RSAVFQQPVI FLGADVTHPP
     AGDGKKPSIT AVVGSMDAHP SRYCATVRVQ RPRQEIIEDL SYMVRELLIQ FYKSTRFKPT
     RIIFYRDGVP EGQLPQILHY ELLAIRDACI KLEKDYQPGI TYIVVQKRHH TRLFCADKNE
     RIGKSGNIPA GTTVDTNITH PFEFDFYLCS HAGIQGTSRP SHYYVLWDDN RFTADELQIL
     TYQLCHTYVR CTRSVSIPAP AYYARLVAFR ARYHLVDKEH DSGEGSHISG QSNGRDPQAL
     AKAVQVHQDT LRTMYFA
//