P56537 (IF6_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Eukaryotic translation initiation factor 6
Short name=eIF-6

Alternative name(s):
B(2)GCN homolog
B4 integrin interactor
CAB
p27(BBP)

Gene names

Name:	EIF6
Synonyms:	EIF3A, ITGB4BP
ORF Names:	OK/SW-cl.27

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	245 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit to form the 80S initiation complex in the cytoplasm. May behave as a stimulatory translation initiation factor downstream insulin/growth factors. Is also involved in ribosome biogenesis. Associates with pre-60S subunits in the nucleus and is involved in its nuclear export. Cytoplasmic release of TIF6 from 60S subunits and nuclear relocalization is promoted by a RACK1 (GNB2L1)-dependent protein kinase C activity. Ref.11 Ref.13 Ref.19
Subunit structure	Monomer. Associates with the 60S ribosomal subunit. Interacts with GNB2L1. Ref.13
Subcellular location	Cytoplasm. Nucleus › nucleolus. Note: Shuttles between cytoplasm and nucleus/nucleolus. Ref.11 Ref.12 Ref.20
Tissue specificity	Expressed at very high levels in colon carcinoma with lower levels in normal colon and ileum and lowest levels in kidney and muscle (at protein level). Ref.3
Post-translational modification	Phosphorylation at Ser-174 and Ser-175 by CSNK1D/CK1 promotes nuclear export. HAMAP-Rule MF_03132
Sequence similarities	Belongs to the eIF-6 family.

Ontologies

Keywords
Biological process	Protein biosynthesis Ribosome biogenesis
Cellular component	Cytoplasm Nucleus
Molecular function	Initiation factor
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	mature ribosome assembly Inferred from mutant phenotype Ref.19. Source: UniProtKB ribosomal large subunit biogenesis Inferred from electronic annotation. Source: HAMAP ribosomal subunit export from nucleus Inferred from electronic annotation. Source: HAMAP
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell lamin filament Inferred from electronic annotation. Source: Compara nucleus Inferred from direct assay. Source: HPA
Molecular_function	ribosomal large subunit binding Inferred from electronic annotation. Source: HAMAP ribosome binding Inferred from direct assay Ref.19. Source: UniProtKB translation initiation factor activity Inferred from electronic annotation. Source: HAMAP
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
DHX58	Q96C10	2	EBI-372243,EBI-744193
EIF2AK2	P19525	2	EBI-372243,EBI-640775
NREP	Q16612	5	EBI-372243,EBI-718657
OAS3	Q9Y6K5	2	EBI-372243,EBI-6115729
Prkcb	P68404	2	EBI-372243,EBI-397048	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 245	245	Eukaryotic translation initiation factor 6 HAMAP-Rule MF_03132		PRO_0000153734
Amino acid modifications
	Modified residue	113	1	Phosphotyrosine Ref.14
	Modified residue	165	1	Phosphothreonine By similarity
	Modified residue	166	1	Phosphoserine By similarity
	Modified residue	174	1	Phosphoserine; by CK1 Ref.12 Ref.20
	Modified residue	175	1	Phosphoserine; by CK1 Ref.12 Ref.20
	Modified residue	235	1	Phosphoserine; by PKC Ref.13
	Modified residue	239	1	Phosphoserine Ref.15 Ref.17
	Modified residue	243	1	Phosphoserine Ref.15
Experimental info
	Sequence conflict	35 – 36	2	Missing in AAK39426. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P56537 [UniParc]. Last modified July 15, 1998. Version 1. Checksum: 5BA97CD5DB0C17C3	FASTA	245	26,599
	10 20 30 40 50 60 MAVRASFENN CEIGCFAKLT NTYCLVAIGG SENFYSVFEG ELSDTIPVVH ASIAGCRIIG 70 80 90 100 110 120 RMCVGNRHGL LVPNNTTDQE LQHIRNSLPD TVQIRRVEER LSALGNVTTC NDYVALVHPD 130 140 150 160 170 180 LDRETEEILA DVLKVEVFRQ TVADQVLVGS YCVFSNQGGL VHPKTSIEDQ DELSSLLQVP 190 200 210 220 230 240 LVAGTVNRGS EVIAAGMVVN DWCAFCGLDT TSTELSVVES VFKLNEAQPS TIATSMRDSL IDSLT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and functional expression of a human cDNA encoding translation initiation factor 6." Si K., Chaudhuri J., Chevesich J., Maitra U. Proc. Natl. Acad. Sci. U.S.A. 94:14285-14290(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Skeletal muscle.
[2]	"Isolation of a novel beta4 integrin-binding protein (p27(BBP)) highly expressed in epithelial cells." Biffo S., Sanvito F., Costa S., Preve L., Pignatelli R., Spinardi L., Marchisio P.C. J. Biol. Chem. 272:30314-30321(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Placenta.
[3]	"The human ITGB4BP gene is constitutively expressed in vitro, but highly modulated in vivo." Donadini A., Giodini A., Sanvito F., Marchisio P.C., Biffo S. Gene 266:35-43(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], TISSUE SPECIFICITY.
[4]	"Identification of genes expressed in human CD34(+) hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning." Mao M., Fu G., Wu J.-S., Zhang Q.-H., Zhou J., Kan L.-X., Huang Q.-H., He K.-L., Gu B.-W., Han Z.-G., Shen Y., Gu J., Yu Y.-P., Xu S.-H., Wang Y.-X., Chen S.-J., Chen Z. Proc. Natl. Acad. Sci. U.S.A. 95:8175-8180(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Umbilical cord blood.
[5]	"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: Placenta.
[6]	"Identification of immuno-peptidmics that are recognized by tumor-reactive CTL generated from TIL of colon cancer patients." Shichijo S., Itoh K. Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon adenocarcinoma.
[7]	"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].
[8]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[10]	"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, Muscle and Ovary.
[11]	"The beta4 integrin interactor p27(BBP/eIF6) is an essential nuclear matrix protein involved in 60S ribosomal subunit assembly." Sanvito F., Piatti S., Villa A., Bossi M., Lucchini G., Marchisio P.C., Biffo S. J. Cell Biol. 144:823-837(1999) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION.
[12]	"Phosphorylation of mammalian eukaryotic translation initiation factor 6 and its Saccharomyces cerevisiae homologue Tif6p: evidence that phosphorylation of Tif6p regulates its nucleocytoplasmic distribution and is required for yeast cell growth." Basu U., Si K., Deng H., Maitra U. Mol. Cell. Biol. 23:6187-6199(2003) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-174 AND SER-175, SUBCELLULAR LOCATION, NUCLEOCYTOPLASMIC SHUTTLING.
[13]	"Release of eIF6 (p27BBP) from the 60S subunit allows 80S ribosome assembly." Ceci M., Gaviraghi C., Gorrini C., Sala L.A., Offenhauser N., Marchisio P.C., Biffo S. Nature 426:579-584(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, PHOSPHORYLATION AT SER-235, INTERACTION WITH GNB2L1.
[14]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-113, MASS SPECTROMETRY.
[15]	"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-239 AND SER-243, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[16]	"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.
[17]	"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[18]	"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].
[19]	"Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes Shwachman-Diamond syndrome." Finch A.J., Hilcenko C., Basse N., Drynan L.F., Goyenechea B., Menne T.F., Gonzalez Fernandez A., Simpson P., D'Santos C.S., Arends M.J., Donadieu J., Bellanne-Chantelot C., Costanzo M., Boone C., McKenzie A.N., Freund S.M., Warren A.J. Genes Dev. 25:917-929(2011) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[20]	"Opposing action of casein kinase 1 and calcineurin in nucleo-cytoplasmic shuttling of mammalian translation initiation factor eIF6." Biswas A., Mukherjee S., Das S., Shields D., Chow C.W., Maitra U. J. Biol. Chem. 286:3129-3138(2011) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION AT SER-174 AND SER-175 BY CSNK1D/CK1, SUBCELLULAR LOCATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF022229 mRNA. Translation: AAB97735.1. Y11435 mRNA. Translation: CAA72243.1. AF289541, AF289540 Genomic DNA. Translation: AAK39426.1. AF047433 mRNA. Translation: AAC39897.1. AK314969 mRNA. Translation: BAG37470.1. AB062289 mRNA. Translation: BAB93472.1. CR456764 mRNA. Translation: CAG33045.1. AL121753 Genomic DNA. Translation: CAX12724.1. CH471077 Genomic DNA. Translation: EAW76221.1. BC001119 mRNA. Translation: AAH01119.1. BC011845 mRNA. Translation: AAH11845.1. BC019305 mRNA. Translation: AAH19305.1.
IPI	IPI00010105.
RefSeq	NP_001254739.1. NM_001267810.1. NP_002203.1. NM_002212.3. NP_852131.1. NM_181466.2. NP_852133.1. NM_181468.2.
UniGene	Hs.654848.
3D structure databases
ProteinModelPortal	P56537.
ModBase	Search...
Protein-protein interaction databases
IntAct	P56537. 11 interactions.
STRING	9606.ENSP00000363559.
Protein family/group databases
Allergome	8361. Hom s eIF6.
PTM databases
PhosphoSite	P56537.
Polymorphism databases
DMDM	3122258.
2D gel databases
OGP	P56537.
REPRODUCTION-2DPAGE	IPI00010105.
SWISS-2DPAGE	P56537.
Proteomic databases
PaxDb	P56537.
PeptideAtlas	P56537.
PRIDE	P56537.
Protocols and materials databases
DNASU	3692.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000374436; ENSP00000363559; ENSG00000242372. ENST00000374450; ENSP00000363574; ENSG00000242372.
GeneID	3692.
KEGG	hsa:3692.
UCSC	uc002xbv.1. human.
Organism-specific databases
CTD	3692.
GeneCards	GC20M033870.
HGNC	HGNC:6159. EIF6.
HPA	HPA040873.
MIM	602912. gene.
neXtProt	NX_P56537.
PharmGKB	PA29958.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1976.
HOGENOM	HOG000230605.
HOVERGEN	HBG001300.
InParanoid	P56537.
KO	K03264.
OMA	QFENSNE.
OrthoDB	EOG4STS5C.
PhylomeDB	P56537.
Gene expression databases
ArrayExpress	P56537.
Bgee	P56537.
CleanEx	HS_EIF3A. HS_EIF6.
Genevestigator	P56537.
GermOnline	ENSG00000126005. Homo sapiens.
Family and domain databases
HAMAP	MF_00032. eIF-6.
InterPro	IPR002769. eIF6. [Graphical view]
PANTHER	PTHR10784. PTHR10784. 1 hit.
Pfam	PF01912. eIF-6. 1 hit. [Graphical view]
PIRSF	PIRSF006413. IF-6. 1 hit.
SMART	SM00654. eIF6. 1 hit. [Graphical view]
TIGRFAMs	TIGR00323. eIF-6. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	EIF6. human.
GenomeRNAi	3692.
NextBio	14465.
SOURCE	Search...

Entry information

Entry name

IF6_HUMAN

Accession

Primary (citable) accession number: P56537
Secondary accession number(s): Q6IBN8, Q96TD5

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 15, 1998
Last sequence update:	July 15, 1998
Last modified:	May 1, 2013
This is version 130 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.