O00303 (EIF3F_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Eukaryotic translation initiation factor 3 subunit F
Short name=eIF3f

Alternative name(s):
Deubiquitinating enzyme eIF3f
EC=3.4.19.12
Eukaryotic translation initiation factor 3 subunit 5
eIF-3-epsilon
eIF3 p47

Gene names

Name:	EIF3F
Synonyms:	EIF3S5

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	357 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is required for several steps in the initiation of protein synthesis. The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S preinitiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation. Ref.17 Deubiquitinates activated NOTCH1, promoting its nuclear import, thereby acting as a positive regulator of Notch signaling. Ref.17
Catalytic activity	Thiol-dependent hydrolysis of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin (a 76-residue protein attached to proteins as an intracellular targeting signal). Ref.17
Subunit structure	Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex interacts with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation leads to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3. Interacts with RNF139; the interaction leads to protein translation inhibitions in a ubiquitination-dependent manner. Interacts with DTX1, the interaction is required for deubiquitinating activity towards NOTCH1. Ref.7 Ref.9 Ref.11 Ref.15 Ref.16 Ref.17
Subcellular location	Cytoplasm By similarity.
Domain	The MPN domain mediates deubiquitinating activity. HAMAP-Rule MF_03005
Post-translational modification	Phosphorylation is enhanced upon serum stimulation. Phosphorylated during apoptosis by caspase-processed CDK11. Ref.6 Ref.11
Sequence similarities	Belongs to the eIF-3 subunit F family. Contains 1 MPN (JAB/Mov34) domain.
Mass spectrometry	Molecular mass is 37554.8 Da from positions 1 - 357. Ref.11 Molecular mass is 37475.6±0.2 Da from positions 1 - 357. Determined by MALDI. Ref.16

Ontologies

Keywords
Biological process	Protein biosynthesis Ubl conjugation pathway
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Molecular function	Hydrolase Initiation factor Protease Thiol protease
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	proteolysis Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	cytosol Traceable author statement. Source: Reactome eukaryotic translation initiation factor 3 complex Inferred from direct assay Ref.11Ref.10Ref.16. Source: UniProtKB
Molecular_function	cysteine-type peptidase activity Inferred from electronic annotation. Source: UniProtKB-KW translation initiation factor activity Traceable author statement Ref.1. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
ORF	Q9Q2G4	3	EBI-711990,EBI-6248094	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Initiator methionine	1	1	Removed Ref.11
	Chain	2 – 357	356	Eukaryotic translation initiation factor 3 subunit F HAMAP-Rule MF_03005		PRO_0000213964
Regions
	Domain	87 – 196	110	MPN
Amino acid modifications
	Modified residue	2	1	N-acetylalanine Ref.11
	Modified residue	46	1	Phosphoserine; by CDK11; in vitro Ref.6
	Modified residue	238	1	N6-acetyllysine Ref.14
	Modified residue	258	1	Phosphoserine Ref.11 Ref.12
Natural variations
	Natural variant	39	1	P → L. Corresponds to variant rs1043738 [ dbSNP | Ensembl ].		VAR_029267
	Natural variant	172	1	W → L. Corresponds to variant rs1044058 [ dbSNP | Ensembl ].		VAR_014452
Experimental info
	Sequence conflict	50 – 56	7	Missing in BAC04577. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	O00303 [UniParc]. Last modified July 1, 1997. Version 1. Checksum: 8A70FC6E2BF07737	FASTA	357	37,564
	10 20 30 40 50 60 MATPAVPVSA PPATPTPVPA AAPASVPAPT PAPAAAPVPA AAPASSSDPA AAAAATAAPG 70 80 90 100 110 120 QTPASAQAPA QTPAPALPGP ALPGPFPGGR VVRLHPVILA SIVDSYERRN EGAARVIGTL 130 140 150 160 170 180 LGTVDKHSVE VTNCFSVPHN ESEDEVAVDM EFAKNMYELH KKVSPNELIL GWYATGHDIT 190 200 210 220 230 240 EHSVLIHEYY SREAPNPIHL TVDTSLQNGR MSIKAYVSTL MGVPGRTMGV MFTPLTVKYA 250 260 270 280 290 300 YYDTERIGVD LIMKTCFSPN RVIGLSSDLQ QVGGASARIQ DALSTVLQYA EDVLSGKVSA 310 320 330 340 350 DNTVGRFLMS LVNQVPKIVP DDFETMLNSN INDLLMVTYL ANLTQSQIAL NEKLVNL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Structure of cDNAs encoding human eukaryotic initiation factor 3 subunits. Possible roles in RNA binding and macromolecular assembly." Asano K., Vornlocher H.-P., Richter-Cook N.J., Merrick W.C., Hinnebusch A.G., Hershey J.W.B. J. Biol. Chem. 272:27042-27052(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[2]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Amygdala and Brain.
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[6]	"The p34cdc2-related cyclin-dependent kinase 11 interacts with the p47 subunit of eukaryotic initiation factor 3 during apoptosis." Shi J., Feng Y., Goulet A.C., Vaillancourt R.R., Sachs N.A., Hershey J.W., Nelson M.A. J. Biol. Chem. 278:5062-5071(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-46.
[7]	"mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events." Holz M.K., Ballif B.A., Gygi S.P., Blenis J. Cell 123:569-580(2005) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RPS6KB1, IDENTIFICATION BY MASS SPECTROMETRY.
[8]	"Binding of eukaryotic initiation factor 3 to ribosomal 40S subunits and its role in ribosomal dissociation and anti-association." Kolupaeva V.G., Unbehaun A., Lomakin I.B., Hellen C.U.T., Pestova T.V. RNA 11:470-486(2005) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF THE EIF-3 COMPLEX.
[9]	"Translation initiation factor eIF4G-1 binds to eIF3 through the eIF3e subunit." LeFebvre A.K., Korneeva N.L., Trutschl M., Cvek U., Duzan R.D., Bradley C.A., Hershey J.W.B., Rhoads R.E. J. Biol. Chem. 281:22917-22932(2006) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE EIF-3 COMPLEX, IDENTIFICATION BY MASS SPECTROMETRY.
[10]	"Reconstitution reveals the functional core of mammalian eIF3." Masutani M., Sonenberg N., Yokoyama S., Imataka H. EMBO J. 26:3373-3383(2007) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF THE EIF-3 COMPLEX.
[11]	"Structural characterization of the human eukaryotic initiation factor 3 protein complex by mass spectrometry." Damoc E., Fraser C.S., Zhou M., Videler H., Mayeur G.L., Hershey J.W.B., Doudna J.A., Robinson C.V., Leary J.A. Mol. Cell. Proteomics 6:1135-1146(2007) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE EIF-3 COMPLEX, CHARACTERIZATION OF THE EIF-3 COMPLEX, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, PHOSPHORYLATION AT SER-258, MASS SPECTROMETRY.
[12]	"A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-258, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[13]	"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions." Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K. Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Leukemic T-cell.
[14]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-238, MASS SPECTROMETRY.
[15]	"The TRC8 ubiquitin ligase is sterol regulated and interacts with lipid and protein biosynthetic pathways." Lee J.P., Brauweiler A., Rudolph M., Hooper J.E., Drabkin H.A., Gemmill R.M. Mol. Cancer Res. 8:93-106(2010) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RNF139.
[16]	"Mass spectrometry reveals modularity and a complete subunit interaction map of the eukaryotic translation factor eIF3." Zhou M., Sandercock A.M., Fraser C.S., Ridlova G., Stephens E., Schenauer M.R., Yokoi-Fong T., Barsky D., Leary J.A., Hershey J.W.B., Doudna J.A., Robinson C.V. Proc. Natl. Acad. Sci. U.S.A. 105:18139-18144(2008) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE EIF-3 COMPLEX, CHARACTERIZATION OF THE EIF-3 COMPLEX, MASS SPECTROMETRY, INTERACTION WITH EIF3B; EIF3H AND EIF3M.
[17]	"The translation initiation factor 3f (eIF3f) exhibits a deubiquitinase activity regulating Notch activation." Moretti J., Chastagner P., Gastaldello S., Heuss S.F., Dirac A.M., Bernards R., Masucci M.G., Israel A., Brou C. PLoS Biol. 8:E1000545-E1000545(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS A DEUBIQUITINATING ENZYME, CATALYTIC ACTIVITY, INTERACTION WITH DTX1.
[18]	"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis." Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M. Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. Tissue: Cervix carcinoma.
[19]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]	"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation." Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B. Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[21]	"Structural roles for human translation factor eIF3 in initiation of protein synthesis." Siridechadilok B., Fraser C.S., Hall R.J., Doudna J.A., Nogales E. Science 310:1513-1515(2005) [PubMed] [Europe PMC] [Abstract] Cited for: 3D-STRUCTURE MODELING, ELECTRON MICROSCOPY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	U94855 mRNA. Translation: AAD03467.1. AK095574 mRNA. Translation: BAC04577.1. AK289637 mRNA. Translation: BAF82326.1. AK291354 mRNA. Translation: BAF84043.1. BT006894 mRNA. Translation: AAP35540.1. CR456959 mRNA. Translation: CAG33240.1. BC000490 mRNA. Translation: AAH00490.1.
IPI	IPI00941255.
RefSeq	NP_003745.1. NM_003754.2.
UniGene	Hs.516023.
3D structure databases
ProteinModelPortal	O00303.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-35580N.
IntAct	O00303. 16 interactions.
MINT	MINT-5000761.
STRING	9606.ENSP00000310040.
Protein family/group databases
MEROPS	M67.974.
PTM databases
PhosphoSite	O00303.
Proteomic databases
PaxDb	O00303.
PRIDE	O00303.
Protocols and materials databases
DNASU	8665.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000309828; ENSP00000310040; ENSG00000175390. ENST00000533626; ENSP00000431800; ENSG00000175390.
GeneID	8665.
KEGG	hsa:8665.
UCSC	uc001mfw.3. human.
Organism-specific databases
CTD	8665.
GeneCards	GC11P007966.
HGNC	HGNC:3275. EIF3F.
HPA	HPA049250.
MIM	603914. gene.
neXtProt	NX_O00303.
PharmGKB	PA162384806.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1310.
HOGENOM	HOG000241154.
HOVERGEN	HBG107843.
InParanoid	O00303.
KO	K03249.
OrthoDB	EOG44XJHN.
PhylomeDB	O00303.
Enzyme and pathway databases
Reactome	REACT_17015. Metabolism of proteins. REACT_1762. 3' -UTR-mediated translational regulation. REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	O00303.
Bgee	O00303.
CleanEx	HS_EIF3F.
Genevestigator	O00303.
GermOnline	ENSG00000175390. Homo sapiens.
Family and domain databases
HAMAP	MF_03005. eIF3f.
InterPro	IPR000555. JAB1_Mov34_MPN_PAD1. IPR024969. Rpn11/EIF3F_C. [Graphical view]
Pfam	PF01398. JAB. 1 hit. PF13012. MitMem_reg. 1 hit. [Graphical view]
SMART	SM00232. JAB_MPN. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	8665.
NextBio	32503.
SOURCE	Search...

Entry information

Entry name

EIF3F_HUMAN

Accession

Primary (citable) accession number: O00303
Secondary accession number(s): A8K0S2, Q6IB45, Q8N978

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	July 1, 1997
Last modified:	May 1, 2013
This is version 125 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.