EIF2C1

Protein argonaute-1 is a protein that in humans is encoded by the EIF2C1 gene.[5][6][7]

AGO1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1SI2, 1SI3, 4KRE, 4KRF, 4KXT
Identifiers
Aliases	AGO1, EIF2C, EIF2C1, GERP95, Q99, hAgo1, argonaute 1, RISC catalytic component, argonaute RISC catalytic component 1, argonaute RISC component 1
External IDs	OMIM: 606228 MGI: 2446630 HomoloGene: 81826 GeneCards: AGO1
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1p34.3 Start 35,869,808 bp[1] End 35,930,532 bp[1]
Gene location (Mouse) Chr. Chromosome 4 (mouse)[2] Band 4|4 D2.2 Start 126,435,012 bp[2] End 126,468,583 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • RNA polymerase II core binding • miRNA binding • endoribonuclease activity • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • GO:0001948 protein binding • single-stranded RNA binding • RNA binding • nucleic acid binding • double-stranded RNA binding Cellular component • cytoplasm • polysome • cytosol • RISC complex • P-body • nucleoplasm • RISC-loading complex • cell nucleus • ribonucleoprotein Biological process • mRNA cleavage involved in gene silencing by siRNA • miRNA loading onto RISC involved in gene silencing by miRNA • regulation of transcription, DNA-templated • transcription, DNA-templated • pre-miRNA processing • nuclear-transcribed mRNA catabolic process • positive regulation of gene expression • posttranscriptional gene silencing by RNA • miRNA mediated inhibition of translation • RNA secondary structure unwinding • mRNA cleavage involved in gene silencing by miRNA • miRNA metabolic process • regulation of translation • positive regulation of transcription from RNA polymerase II promoter • production of miRNAs involved in gene silencing by miRNA • positive regulation of NIK/NF-kappaB signaling • Wnt signaling pathway, calcium modulating pathway • gene silencing by RNA • regulation of gene silencing by miRNA • regulation of megakaryocyte differentiation • negative regulation of gene expression • negative regulation of angiogenesis • RNA phosphodiester bond hydrolysis, endonucleolytic Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	26523	236511
Ensembl	ENSG00000092847	ENSMUSG00000041530
UniProt	Q9UL18	Q8CJG1
RefSeq (mRNA)	NM_012199 NM_001317122 NM_001317123	NM_153403 NM_001317173 NM_001317174 NM_001378879
RefSeq (protein)	NP_001304051 NP_001304052 NP_036331	NP_001304102 NP_001304103 NP_700452 NP_001365808
Location (UCSC)	Chr 1: 35.87 – 35.93 Mb	Chr 4: 126.44 – 126.47 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

This gene encodes a member of the Argonaute family of proteins which play a role in RNA interference. The encoded protein is highly basic, and contains a PAZ domain and a PIWI domain. It may interact with dicer1 and play a role in short-interfering-RNA-mediated gene silencing. This gene is located on chromosome 1 in a cluster of closely related family members including argonaute 3, and argonaute 4.[7]

Model organisms

Eif2c1 knockout mouse phenotype

Characteristic	Phenotype
Homozygote viability	Abnormal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Abnormal
Haematology	Normal
Micronucleus test	Normal
Heart weight	Normal
Eye Histopathology	Normal
Salmonella infection	Normal[8]
Citrobacter infection	Normal[9]
All tests and analysis from[10][11]

Model organisms have been used in the study of EIF2C1 function. A conditional knockout mouse line, called Eif2c1^{tm1a(KOMP)Wtsi}[12][13] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.[14][15][16]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.[10][17] Twenty two tests were carried out on mutant mice and two significant abnormalities were observed: homozygous mutants were subviable and females also had decreased circulating aspartate transaminase levels. [10]

References

1. GRCh38: Ensembl release 89: ENSG00000092847 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000041530 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Koesters R, Adams V, Betts D, Moos R, Schmid M, Siermann A, Hassam S, Weitz S, Lichter P, Heitz PU, von Knebel Doeberitz M, Briner J (Oct 1999). "Human eukaryotic initiation factor EIF2C1 gene: cDNA sequence, genomic organization, localization to chromosomal bands 1p34-p35, and expression". Genomics. 61 (2): 210–8. doi:10.1006/geno.1999.5951. PMID 10534406.
6. Sasaki T, Shiohama A, Minoshima S, Shimizu N (Sep 2003). "Identification of eight members of the Argonaute family in the human genome". Genomics. 82 (3): 323–30. doi:10.1016/S0888-7543(03)00129-0. PMID 12906857.
7. "Entrez Gene: EIF2C1 eukaryotic translation initiation factor 2C, 1".
8. "Salmonella infection data for Eif2c1". Wellcome Trust Sanger Institute.
9. "Citrobacter infection data for Eif2c1". Wellcome Trust Sanger Institute.
10. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
11. Mouse Resources Portal, Wellcome Trust Sanger Institute.
12. "International Knockout Mouse Consortium".
13. "Mouse Genome Informatics".
14. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
15. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
16. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
17. van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

Further reading

• Carmell MA, Xuan Z, Zhang MQ, Hannon GJ (Nov 2002). "The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis". Genes & Development. 16 (21): 2733–42. doi:10.1101/gad.1026102. PMID 12414724.
• Reddy PH, Stockburger E, Gillevet P, Tagle DA (Dec 1997). "Mapping and characterization of novel (CAG)n repeat cDNAs from adult human brain derived by the oligo capture method" (PDF). Genomics. 46 (2): 174–82. doi:10.1006/geno.1997.5044. PMID 9417904.
• Cikaluk DE, Tahbaz N, Hendricks LC, DiMattia GE, Hansen D, Pilgrim D, Hobman TC (Oct 1999). "GERp95, a membrane-associated protein that belongs to a family of proteins involved in stem cell differentiation". Molecular Biology of the Cell. 10 (10): 3357–72. doi:10.1091/mbc.10.10.3357. PMC 25603. PMID 10512872.
• Martinez J, Patkaniowska A, Urlaub H, Lührmann R, Tuschl T (Sep 2002). "Single-stranded antisense siRNAs guide target RNA cleavage in RNAi". Cell. 110 (5): 563–74. doi:10.1016/S0092-8674(02)00908-X. hdl:11858/00-001M-0000-0012-F2FD-2. PMID 12230974.
• Doi N, Zenno S, Ueda R, Ohki-Hamazaki H, Ui-Tei K, Saigo K (Jan 2003). "Short-interfering-RNA-mediated gene silencing in mammalian cells requires Dicer and eIF2C translation initiation factors". Current Biology. 13 (1): 41–6. doi:10.1016/S0960-9822(02)01394-5. PMID 12526743.
• Ma JB, Ye K, Patel DJ (May 2004). "Structural basis for overhang-specific small interfering RNA recognition by the PAZ domain". Nature. 429 (6989): 318–22. doi:10.1038/nature02519. PMC 4700412. PMID 15152257.
• Sen GL, Blau HM (Jun 2005). "Argonaute 2/RISC resides in sites of mammalian mRNA decay known as cytoplasmic bodies". Nature Cell Biology. 7 (6): 633–6. doi:10.1038/ncb1265. PMID 15908945.
• Liu J, Valencia-Sanchez MA, Hannon GJ, Parker R (Jul 2005). "MicroRNA-dependent localization of targeted mRNAs to mammalian P-bodies". Nature Cell Biology. 7 (7): 719–23. doi:10.1038/ncb1274. PMC 1855297. PMID 15937477.
• Chu CY, Rana TM (Jul 2006). "Translation repression in human cells by microRNA-induced gene silencing requires RCK/p54". PLoS Biology. 4 (7): e210. doi:10.1371/journal.pbio.0040210. PMC 1475773. PMID 16756390.
• Kim DH, Villeneuve LM, Morris KV, Rossi JJ (Sep 2006). "Argonaute-1 directs siRNA-mediated transcriptional gene silencing in human cells". Nature Structural & Molecular Biology. 13 (9): 793–7. doi:10.1038/nsmb1142. PMID 16936726.
• Janowski BA, Huffman KE, Schwartz JC, Ram R, Nordsell R, Shames DS, Minna JD, Corey DR (Sep 2006). "Involvement of AGO1 and AGO2 in mammalian transcriptional silencing". Nature Structural & Molecular Biology. 13 (9): 787–92. doi:10.1038/nsmb1140. PMID 16936728.
• Sasaki T, Shimizu N (Jul 2007). "Evolutionary conservation of a unique amino acid sequence in human DICER protein essential for binding to Argonaute family proteins". Gene. 396 (2): 312–20. doi:10.1016/j.gene.2007.04.001. PMID 17482383.