InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Eif2c2

Summary

InnateDB Protein

IDBP-148174.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Eif2c2

Protein Name

eukaryotic translation initiation factor 2C, 2

Synonyms

Species

Mus musculus

Ensembl Protein

ENSMUSP00000042207

InnateDB Gene

IDBG-148172 (Eif2c2)

Protein Structure

UniProt Annotation

Function

Required for RNA-mediated gene silencing (RNAi) by the RNA-induced silencing complex (RISC). The 'minimal RISC' appears to include AGO2 bound to a short guide RNA such as a microRNA (miRNA) or short interfering RNA (siRNA). These guide RNAs direct RISC to complementary mRNAs that are targets for RISC-mediated gene silencing. The precise mechanism of gene silencing depends on the degree of complementarity between the miRNA or siRNA and its target. Binding of RISC to a perfectly complementary mRNA generally results in silencing due to endonucleolytic cleavage of the mRNA specifically by AGO2. Binding of RISC to a partially complementary mRNA results in silencing through inhibition of translation, and this is independent of endonuclease activity. May inhibit translation initiation by binding to the 7-methylguanosine cap, thereby preventing the recruitment of the translation initiation factor eIF4-E. May also inhibit translation initiation via interaction with EIF6, which itself binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit. The inhibition of translational initiation leads to the accumulation of the affected mRNA in cytoplasmic processing bodies (P-bodies), where mRNA degradation may subsequently occur. In some cases RISC-mediated translational repression is also observed for miRNAs that perfectly match the 3' untranslated region (3'-UTR). Can also up-regulate the translation of specific mRNAs under certain growth conditions. Binds to the AU element of the 3'-UTR of the TNF (TNF-alpha) mRNA and up-regulates translation under conditions of serum starvation. Also required for transcriptional gene silencing (TGS), in which short RNAs known as antigene RNAs or agRNAs direct the transcriptional repression of complementary promoter regions. Regulates lymphoid and erythroid development and function, and this is independent of endonuclease activity. {ECO:0000269PubMed:15284456, ECO:0000269PubMed:17626790, ECO:0000269PubMed:19174539}.

Subcellular Localization

Cytoplasm, P-body {ECO:0000255HAMAP- Rule:MF_03031}. Nucleus {ECO:0000255HAMAP-Rule:MF_03031}. Note=Translational repression of mRNAs results in their recruitment to P-bodies. Translocation to the nucleus requires IMP8. {ECO:0000255HAMAP-Rule:MF_03031}.

Disease Associations

Tissue Specificity

Ubiquitous expression in 9.5 day embryos with highest levels in forebrain, heart, limb buds, and branchial arches. {ECO:0000269PubMed:15284456}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 24 experimentally validated interaction(s) in this database.
They are also associated with 74 interaction(s) predicted by orthology.

Experimentally validated
Total	24 [view]
Protein-Protein	23 [view]
Protein-DNA	0
Protein-RNA	1 [view]
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	74 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000340	RNA 7-methylguanosine cap binding
GO:0003676	nucleic acid binding
GO:0003723	RNA binding
GO:0003729	mRNA binding
GO:0004521	endoribonuclease activity
GO:0005515	protein binding
GO:0035197	siRNA binding
GO:0035198	miRNA binding
GO:0044822	poly(A) RNA binding
GO:0046872	metal ion binding
GO:0070551	endoribonuclease activity, cleaving siRNA-paired mRNA

Biological Process

GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0006379	mRNA cleavage
GO:0009791	post-embryonic development
GO:0030154	cell differentiation
GO:0031047	gene silencing by RNA
GO:0031054	pre-miRNA processing
GO:0035278	negative regulation of translation involved in gene silencing by miRNA
GO:0035279	mRNA cleavage involved in gene silencing by miRNA
GO:0045947	negative regulation of translational initiation
GO:0060213	positive regulation of nuclear-transcribed mRNA poly(A) tail shortening
GO:0090502	RNA phosphodiester bond hydrolysis, endonucleolytic
GO:1900153	positive regulation of nuclear-transcribed mRNA catabolic process, deadenylation-dependent decay

Cellular Component

GO:0000932	cytoplasmic mRNA processing body
GO:0005634	nucleus
GO:0005737	cytoplasm
GO:0005844	polysome
GO:0005845	mRNA cap binding complex
GO:0016020	membrane
GO:0016442	RISC complex
GO:0030529	ribonucleoprotein complex
GO:0035068	micro-ribonucleoprotein complex

Protein Structure and Domains

PDB ID

MGI:2446632

InterPro

IPR003100 Argonaute/Dicer protein, PAZ domain
IPR003165 Stem cell self-renewal protein Piwi
IPR012337 Ribonuclease H-like domain
IPR014811 Domain of unknown function DUF1785

PFAM

PF02170
PF02171
PF08699

PRINTS

PIRSF

SMART

SM00949
SM00950

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

Q8CJG0