EIF3C (eukaryotic translation initiation factor 3, subunit C)

2008-02-01   Daniel R Scoles 

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

Identity

HGNC
LOCATION
16p11.2
LOCUSID
ALIAS
EIF3CL,EIF3S8,eIF3-p110

DNA/RNA

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.

Proteins

Atlas Image
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).

Mutations

Note

No eIF3c mutations have been reported.

Implicated in

Entity name
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).

Bibliography

Pubmed IDLast YearTitleAuthors
89954091997Conservation and diversity of eukaryotic translation initiation factor eIF3.Asano K et al
120307602002A method for the rapid construction of cRNA standard curves in quantitative real-time reverse transcription polymerase chain reaction.Fronhoffs S et al
128610282003The yeast eukaryotic initiation factor 4G (eIF4G) HEAT domain interacts with eIF1 and eIF5 and is involved in stringent AUG selection.He H et al
169203602006eIF3: a versatile scaffold for translation initiation complexes.Hinnebusch AG et al
104938291999Genome duplications and other features in 12 Mb of DNA sequence from human chromosome 16p and 16q.Loftus BJ et al
110738192000Eukaryotic initiation factor 3 p110 mRNA is overexpressed in testicular seminomas.Rothe M et al
179801642008The merlin interacting proteins reveal multiple targets for NF2 therapy.Scoles DR et al
164977272006Schwannomin inhibits tumorigenesis through direct interaction with the eukaryotic initiation factor subunit c (eIF3c).Scoles DR et al
160231662005Induction and mode of action of the viral stress-inducible murine proteins, P56 and P54.Terenzi F et al
110294662001Arabidopsis eIF3e (INT-6) associates with both eIF3c and the COP9 signalosome subunit CSN7.Yahalom A et al
171701152007Individual overexpression of five subunits of human translation initiation factor eIF3 promotes malignant transformation of immortal fibroblast cells.Zhang L et al

Other Information

Locus ID:

NCBI: 8663
MIM: 603916
HGNC: 3279
Ensembl: ENSG00000184110

Variants:

dbSNP: 8663
ClinVar: 8663
TCGA: ENSG00000184110
COSMIC: EIF3C

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000184110ENST00000331666Q99613
ENSG00000184110ENST00000331666A0A024QYU9
ENSG00000184110ENST00000395587Q99613
ENSG00000184110ENST00000395587A0A024QYU9
ENSG00000184110ENST00000563139H3BTY8
ENSG00000184110ENST00000564243Q99613
ENSG00000184110ENST00000566501Q99613
ENSG00000184110ENST00000566501A0A024QYU9
ENSG00000184110ENST00000566866Q99613
ENSG00000184110ENST00000566866A0A024QYU9
ENSG00000184110ENST00000568426H3BPE3
ENSG00000184110ENST00000569690H3BPE4

Expression (GTEx)

0
5
10
15

Pathways

PathwaySourceExternal ID
RNA transportKEGGko03013
RNA transportKEGGhsa03013
Metabolism of proteinsREACTOMER-HSA-392499
TranslationREACTOMER-HSA-72766
Eukaryotic Translation InitiationREACTOMER-HSA-72613
Cap-dependent Translation InitiationREACTOMER-HSA-72737
Formation of a pool of free 40S subunitsREACTOMER-HSA-72689
Formation of the ternary complex, and subsequently, the 43S complexREACTOMER-HSA-72695
Activation of the mRNA upon binding of the cap-binding complex and eIFs, and subsequent binding to 43SREACTOMER-HSA-72662
Translation initiation complex formationREACTOMER-HSA-72649
Ribosomal scanning and start codon recognitionREACTOMER-HSA-72702
GTP hydrolysis and joining of the 60S ribosomal subunitREACTOMER-HSA-72706
L13a-mediated translational silencing of Ceruloplasmin expressionREACTOMER-HSA-156827
Gene ExpressionREACTOMER-HSA-74160

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
240927552013Human eukaryotic initiation factor 4G (eIF4G) protein binds to eIF3c, -d, and -e to promote mRNA recruitment to the ribosome.48
249126832014Functional and biochemical characterization of human eukaryotic translation initiation factor 3 in living cells.35
303625622019Overexpressed circ_0067934 acts as an oncogene to facilitate cervical cancer progression via the miR-545/EIF3C axis.18
282314102017Transcriptomic analyses of RNA-binding proteins reveal eIF3c promotes cell proliferation in hepatocellular carcinoma.12
237334212013Effect of siRNA-mediated knockdown of eIF3c gene on survival of colon cancer cells.11
258235032015Eukaryotic initiation factor 3C silencing inhibits cell proliferation and promotes apoptosis in human glioma.9
288541632017Decreasing Eukaryotic Initiation Factor 3C (EIF3C) Suppresses Proliferation and Stimulates Apoptosis in Breast Cancer Cell Lines Through Mammalian Target of Rapamycin (mTOR) Pathway.9
220160362012The interaction between human initiation factor eIF3 subunit c and heat-shock protein 90: a necessary factor for translation mediated by the hepatitis C virus internal ribosome entry site.3
311819672019The Prognostic Significance of EIF3C Gene during the Tumorigenesis of Prostate Cancer.2
318635852020Adapted formaldehyde gradient cross-linking protocol implicates human eIF3d and eIF3c, k and l subunits in the 43S and 48S pre-initiation complex assembly, respectively.1

Citation

Daniel R Scoles

EIF3C (eukaryotic translation initiation factor 3, subunit C)

Atlas Genet Cytogenet Oncol Haematol. 2008-02-01

Online version: http://atlasgeneticsoncology.org/gene/44187/eif3c