EIF2C1

Argonaute RISC catalytic component 1
PDB rendering based on 1si2.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1SI2​, 1SI3​, 4KRE​, 4KRF​, 4KXT​
Identifiers
Symbols	AGO1 ; EIF2C; EIF2C1; GERP95; Q99
External IDs	OMIM: 606228 MGI: 2446630 HomoloGene: 81826 GeneCards: AGO1 Gene
Gene ontology Molecular function • RNA polymerase II core promoter proximal region sequence-specific DNA binding • RNA polymerase II core binding • core promoter binding • RNA binding • double-stranded RNA binding • single-stranded RNA binding • endoribonuclease activity • protein binding • miRNA binding • poly(A) RNA binding • pre-miRNA binding Cellular component • cytoplasmic mRNA processing body • nucleus • nucleoplasm • cytoplasm • cytosol • polysome • RISC complex • ribonucleoprotein complex • micro-ribonucleoprotein complex • RISC-loading complex Biological process • nuclear-transcribed mRNA catabolic process • transcription, DNA-templated • epidermal growth factor receptor signaling pathway • Notch signaling pathway • fibroblast growth factor receptor signaling pathway • gene expression • RNA secondary structure unwinding • miRNA metabolic process • posttranscriptional gene silencing • pre-miRNA processing • production of miRNAs involved in gene silencing by miRNA • negative regulation of translation involved in gene silencing by miRNA • mRNA cleavage involved in gene silencing by miRNA • miRNA loading onto RISC involved in gene silencing by miRNA • Fc-epsilon receptor signaling pathway • innate immune response • positive regulation of transcription from RNA polymerase II promoter • neurotrophin TRK receptor signaling pathway • phosphatidylinositol-mediated signaling • mRNA cleavage involved in gene silencing by siRNA Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	26523	236511
Ensembl	ENSG00000092847	ENSMUSG00000041530
UniProt	Q9UL18	Q8CJG1
RefSeq (mRNA)	NM_012199	NM_153403
RefSeq (protein)	NP_036331	NP_700452
Location (UCSC)	Chr 1: 35.87 – 35.93 Mb	Chr 4: 126.44 – 126.47 Mb
PubMed search

Protein argonaute-1 is a protein that in humans is encoded by the EIF2C1 gene.^[1][2][3]

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.^[3]

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[4]
Citrobacter infection	Normal[5]
All tests and analysis from[6][7]

Model organisms have been used in the study of EIF2C1 function. A conditional knockout mouse line, called Eif2c1^{tm1a(KOMP)Wtsi[8][9]} 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.^[10][11][12]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[6][13] 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. ^[6]

References

1. 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.
2. 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.
3. "Entrez Gene: EIF2C1 eukaryotic translation initiation factor 2C, 1".
4. "Salmonella infection data for Eif2c1". Wellcome Trust Sanger Institute.
5. "Citrobacter infection data for Eif2c1". Wellcome Trust Sanger Institute.
6. 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.
7. Mouse Resources Portal, Wellcome Trust Sanger Institute.
8. "International Knockout Mouse Consortium".
9. "Mouse Genome Informatics".
10. 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.
11. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
12. 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.
13. 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". 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. 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. 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.