EIF3C (eukaryotic translation initiation factor 3, subunit C)

Written2008-02Daniel R Scoles
Division of Neurology, CSMC Burns, Allen Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 9, USA

(Note : for Links provided by Atlas : click)

1. Identity

General Information
eukaryotic translation initiation factor 3, subunit 8, 110kDa
eukaryotic translation initiation factor 3, subunit C
Alias_symbol (synonym)eIF3-p110
Other aliaseIF3 subunit p110
LocusID (NCBI) 8663
Atlas_Id 44187
Location 16p11.2  [Link to chromosome band 16p11]
Location_base_pair Starts at 28379582 and ends at 28403888 bp from pter ( according to hg19-Feb_2009)  [Mapping EIF3C.png]
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
Note eIF3c is one of 12 subunit proteins comprising the eukaryotic initiation factor 3 (eIF3) complex.


Description The EIF3C gene is composed of 21 exons. No alternative splicing has been reported for eIF3c.
The EIF3C gene is located on chromosome 16p11.2 within an unstable region prone to duplication, and intact duplication of the entire EIF3C gene has been demonstrated in multiple tissue types. One mechanism of eIF3c overexpression, observed in various tumor types, may be gene duplication.

3. Protein

  Schematic of the 913 amino acid eIF3c protein with amino acid positions shown and locations of the PCI domain. Also indicated are the known minimal regions in eIF3c required for binding by interacting proteins. These include eIF complexes eIF1 and eIF5, the NF2 tumor suppressor merlin, and murine viral stress mediated inhibitors of protein translation MuP56 and MuP54. For merlin, the broken line indicates a region promoting stronger merlin binding when included. Note that eIF3c also binds the COP9 signalosome protein CSN7 in Arabidopsis, which may mediate inhibition of protein translation.
Description The eIF3c protein is 913 amino acids in length. The eIF3c protein possesses the PCI (proteasome component region) domain within its C-terminal half (also referred to as PINT domain). Domain searching reveals that EIF3c also possesses a winged helix repressor DNA-binding domain overlapping with the PCI domain.
Expression Ubiquitous.
Localisation eIF3c is cytoplasmic. There is some evidence of eIF3c occurring in the nucleus consistent with reports of intranuclear protein translation as well as regulation of protein translation by interaction with the COP9 signalosome.
Function The initiation of protein translation is a complex sequence of events mediated by the interaction of eIF3 with phosphorylated mTOR . Multiple interactions by eIF3 subsequently take place during the progression of protein translation initiation including the proper positioning of the preinitiation complex on the 40S ribosome mediated by eIF3. EIF3c has a significant role in binding to two AUG recognition factors, eIF1 and eIF5, and these interactions are required for proper AUG scanning by the preinitiation complex.
EIF3c is overexpressed in some tumors including seminomas and meningiomas. EIF3c can also interact with the neurofibromatosis 2 (NF2) tumor suppressor merlin (schwannomin) and merlin can inhibit eIF3c mediated cell proliferation. In meningiomas eIF3c expression was inversely related to merlin expression and was overexpressed in meningiomas that had lost merlin expression. EIF3c overexpression can also transform NIH/3T3 fibroblasts, indicated by decreased doubling times, increased clonogenicity, increased viability, facilitated S-phase entry, attenuated apoptosis, formation of transformed foci, and anchorage-independent growth.
Murine EIF3c is also a target of inhibitory proteins induced by viral stress. Viral induced MuP56 and MuP54 bind eIF3c in different locations resulting in protein translation inhibition.
In Arabidopsis, eIF3c also interacts with the COP9 signalosome subunit CSN7 in the nucleus. COP9 binding is thought to be associated with downregulated protein translation. eIF3c possesses the PCI domain common among proteasome member proteins and also found in other eIF subunit proteins.
Homology eIF3c is the homolog to yeast NIP1 (37% identity).

4. Mutations

Note No eIF3c mutations have been reported.

5. Implicated in

Entity Various Cancer
Oncogenesis eIF3c has been noted overexpressed in a subset of testicular tumors (seminomas). EIF3c has also been shown overexpressed in meningiomas that have lost expression of the neurofibromatosis 2 tumor suppressor merlin (approximately 50% of sporadic meningiomas).

6. To be noted

eIF3c is an oncoprotein overexpressed in tumors. As such eIF3c is a potential therapeutic target. eIF3c may be a particularly good therapeutic target for NF2 since all tumors that had lost merlin function had overexpressed eIF3c.

7. Bibliography

Conservation and diversity of eukaryotic translation initiation factor eIF3.
Asano K, Kinzy TG, Merrick WC, Hershey JW
The Journal of biological chemistry. 1997 ; 272 (2) : 1101-1109.
PMID 8995409
A method for the rapid construction of cRNA standard curves in quantitative real-time reverse transcription polymerase chain reaction.
Fronhoffs S, Totzke G, Stier S, Wernert N, Rothe M, Brüning T, Koch B, Sachinidis A, Vetter H, Ko Y
Molecular and cellular probes. 2002 ; 16 (2) : 99-110.
PMID 12030760
The yeast eukaryotic initiation factor 4G (eIF4G) HEAT domain interacts with eIF1 and eIF5 and is involved in stringent AUG selection.
He H, von der Haar T, Singh CR, Ii M, Li B, Hinnebusch AG, McCarthy JE, Asano K
Molecular and cellular biology. 2003 ; 23 (15) : 5431-5445.
PMID 12861028
eIF3: a versatile scaffold for translation initiation complexes.
Hinnebusch AG
Trends in biochemical sciences. 2006 ; 31 (10) : 553-562.
PMID 16920360
Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q.
Loftus BJ, Kim UJ, Sneddon VP, Kalush F, Brandon R, Fuhrmann J, Mason T, Crosby ML, Barnstead M, Cronin L, Deslattes Mays A, Cao Y, Xu RX, Kang HL, Mitchell S, Eichler EE, Harris PC, Venter JC, Adams MD
Genomics. 1999 ; 60 (3) : 295-308.
PMID 10493829
Eukaryotic initiation factor 3 p110 mRNA is overexpressed in testicular seminomas.
Rothe M, Ko Y, Albers P, Wernert N
The American journal of pathology. 2000 ; 157 (5) : 1597-1604.
PMID 11073819
The merlin interacting proteins reveal multiple targets for NF2 therapy.
Scoles DR
Biochimica et biophysica acta. 2008 ; 1785 (1) : 32-54.
PMID 17980164
Schwannomin inhibits tumorigenesis through direct interaction with the eukaryotic initiation factor subunit c (eIF3c).
Scoles DR, Yong WH, Qin Y, Wawrowsky K, Pulst SM
Human molecular genetics. 2006 ; 15 (7) : 1059-1070.
PMID 16497727
Induction and mode of action of the viral stress-inducible murine proteins, P56 and P54.
Terenzi F, Pal S, Sen GC
Virology. 2005 ; 340 (1) : 116-124.
PMID 16023166
Arabidopsis eIF3e (INT-6) associates with both eIF3c and the COP9 signalosome subunit CSN7.
Yahalom A, Kim TH, Winter E, Karniol B, von Arnim AG, Chamovitz DA
The Journal of biological chemistry. 2001 ; 276 (1) : 334-340.
PMID 11029466
Individual overexpression of five subunits of human translation initiation factor eIF3 promotes malignant transformation of immortal fibroblast cells.
Zhang L, Pan X, Hershey JW
The Journal of biological chemistry. 2007 ; 282 (8) : 5790-5800.
PMID 17170115

8. Citation

This paper should be referenced as such :
Scoles, Daniel R
EIF3C (eukaryotic translation initiation factor 3, subunit C)
Atlas Genet Cytogenet Oncol Haematol. 2008;12(6):428-429.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://atlasgeneticsoncology.usal.es/classic/Genes/EIF3CID44187ch16p11.html

9. External links

HGNC (Hugo)EIF3C   3279
Entrez_Gene (NCBI)EIF3C  8663  eukaryotic translation initiation factor 3 subunit C
AliasesEIF3CL; EIF3S8; eIF3-p110
GeneCards (Weizmann)EIF3C
Ensembl hg19 (Hinxton)ENSG00000184110 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000184110 [Gene_View] &nbspENSG00000184110 [Sequence]  chr16:28379582-28403888 [Contig_View]  EIF3C [Vega]
ICGC DataPortalENSG00000184110
TCGA cBioPortalEIF3C
Genatlas (Paris)EIF3C
SOURCE (Princeton)EIF3C
Genetics Home Reference (NIH)EIF3C
Genomic and cartography
GoldenPath hg38 (UCSC)EIF3C  -     chr16:28379582-28403888 -  16p11.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)EIF3C  -     16p11.2   [Description]    (hg19-Feb_2009)
EnsemblEIF3C - 16p11.2 [CytoView hg19]  EIF3C - 16p11.2 [CytoView hg38]
Mapping of homologs : NCBIEIF3C [Mapview hg19]  EIF3C [Mapview hg38]
Gene and transcription
Genbank (Entrez)AA679705 AK000739 AK055366 AK130531 AK292155
RefSeq transcript (Entrez)NM_001037808 NM_001199142 NM_001267574 NM_001286478 NM_003752
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)EIF3C
Cluster EST : UnigeneHs.567374 [ NCBI ]
CGAP (NCI)Hs.567374
Alternative Splicing GalleryENSG00000184110
Gene ExpressionEIF3C [ NCBI-GEO ]   EIF3C [ EBI - ARRAY_EXPRESS ]   EIF3C [ SEEK ]   EIF3C [ MEM ]
Gene Expression Viewer (FireBrowse)EIF3C [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets] &nbsp [Normal Tissue Atlas] &nbsp[carcinoma Classsification] &nbsp[NCI60]
GenevestigatorExpression in : [tissues] &nbsp[cell-lines] &nbsp[cancer] &nbsp[perturbations] &nbsp
BioGPS (Tissue expression)8663
GTEX Portal (Tissue expression)EIF3C
Human Protein AtlasENSG00000184110-EIF3C [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ99613   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ99613  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ99613
Splice isoforms : SwissVarQ99613
Domaine pattern : Prosite (Expaxy)PCI (PS50250)   
Domains : Interpro (EBI)EIF3C    EIF3C_N_dom    PCI_dom    WH-like_DNA-bd_sf    WH_DNA-bd_sf   
Domain families : Pfam (Sanger)eIF-3c_N (PF05470)    PCI (PF01399)   
Domain families : Pfam (NCBI)pfam05470    pfam01399   
Domain families : Smart (EMBL)PINT (SM00088)  
Conserved Domain (NCBI)EIF3C
DMDM Disease mutations8663
Blocks (Seattle)EIF3C
PDB (RSDB)3J8B    3J8C   
PDB Europe3J8B    3J8C   
PDB (PDBSum)3J8B    3J8C   
PDB (IMB)3J8B    3J8C   
Structural Biology KnowledgeBase3J8B    3J8C   
SCOP (Structural Classification of Proteins)3J8B    3J8C   
CATH (Classification of proteins structures)3J8B    3J8C   
Human Protein Atlas [tissue]ENSG00000184110-EIF3C [tissue]
Peptide AtlasQ99613
Protein Interaction databases
IntAct (EBI)Q99613
Ontologies - Pathways
Ontology : AmiGOformation of cytoplasmic translation initiation complex  RNA binding  translation initiation factor activity  translation initiation factor activity  translation initiation factor activity  protein binding  cytosol  eukaryotic translation initiation factor 3 complex  eukaryotic translation initiation factor 3 complex  translational initiation  translational initiation  translational initiation  translational initiation  eukaryotic 43S preinitiation complex  translation initiation factor binding  eukaryotic 48S preinitiation complex  positive regulation of translation  positive regulation of mRNA binding  
Ontology : EGO-EBIformation of cytoplasmic translation initiation complex  RNA binding  translation initiation factor activity  translation initiation factor activity  translation initiation factor activity  protein binding  cytosol  eukaryotic translation initiation factor 3 complex  eukaryotic translation initiation factor 3 complex  translational initiation  translational initiation  translational initiation  translational initiation  eukaryotic 43S preinitiation complex  translation initiation factor binding  eukaryotic 48S preinitiation complex  positive regulation of translation  positive regulation of mRNA binding  
Pathways : KEGGRNA transport   
NDEx NetworkEIF3C
Atlas of Cancer Signalling NetworkEIF3C
Wikipedia pathwaysEIF3C
Orthology - Evolution
GeneTree (enSembl)ENSG00000184110
Phylogenetic Trees/Animal Genes : TreeFamEIF3C
Homologs : HomoloGeneEIF3C
Homology/Alignments : Family Browser (UCSC)EIF3C
Gene fusions - Rearrangements
Fusion : QuiverEIF3C
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerEIF3C [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)EIF3C
Exome Variant ServerEIF3C
ExAC (Exome Aggregation Consortium)ENSG00000184110
GNOMAD BrowserENSG00000184110
Varsome BrowserEIF3C
Genetic variants : HAPMAP8663
Genomic Variants (DGV)EIF3C [DGVbeta]
DECIPHEREIF3C [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisEIF3C 
ICGC Data PortalEIF3C 
TCGA Data PortalEIF3C 
Broad Tumor PortalEIF3C
OASIS PortalEIF3C [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICEIF3C  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDEIF3C
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch EIF3C
DgiDB (Drug Gene Interaction Database)EIF3C
DoCM (Curated mutations)EIF3C (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)EIF3C (select a term)
NCG5 (London)EIF3C
Cancer3DEIF3C(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry EIF3C
NextProtQ99613 [Medical]
Target ValidationEIF3C
Huge Navigator EIF3C [HugePedia]
snp3D : Map Gene to Disease8663
BioCentury BCIQEIF3C
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD8663
Chemical/Pharm GKB GenePA162384646
Clinical trialEIF3C
canSAR (ICR)EIF3C (select the gene name)
DataMed IndexEIF3C
PubMed89 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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