Full text data of EIF6
EIF6
(EIF3A, ITGB4BP)
[Confidence: low (only semi-automatic identification from reviews)]
Eukaryotic translation initiation factor 6; eIF-6 (B(2)GCN homolog; B4 integrin interactor; CAB; p27(BBP))
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Eukaryotic translation initiation factor 6; eIF-6 (B(2)GCN homolog; B4 integrin interactor; CAB; p27(BBP))
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P56537
ID IF6_HUMAN Reviewed; 245 AA.
AC P56537; B7ZBG9; Q6IBN8; Q96TD5;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
read moreDT 15-JUL-1998, sequence version 1.
DT 22-JAN-2014, entry version 137.
DE RecName: Full=Eukaryotic translation initiation factor 6;
DE Short=eIF-6;
DE AltName: Full=B(2)GCN homolog;
DE AltName: Full=B4 integrin interactor;
DE AltName: Full=CAB;
DE AltName: Full=p27(BBP);
GN Name=EIF6; Synonyms=EIF3A, ITGB4BP; ORFNames=OK/SW-cl.27;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Skeletal muscle;
RX PubMed=9405604; DOI=10.1073/pnas.94.26.14285;
RA Si K., Chaudhuri J., Chevesich J., Maitra U.;
RT "Molecular cloning and functional expression of a human cDNA encoding
RT translation initiation factor 6.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:14285-14290(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=9374518; DOI=10.1074/jbc.272.48.30314;
RA Biffo S., Sanvito F., Costa S., Preve L., Pignatelli R., Spinardi L.,
RA Marchisio P.C.;
RT "Isolation of a novel beta4 integrin-binding protein (p27(BBP)) highly
RT expressed in epithelial cells.";
RL J. Biol. Chem. 272:30314-30321(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX PubMed=11290417; DOI=10.1016/S0378-1119(01)00370-5;
RA Donadini A., Giodini A., Sanvito F., Marchisio P.C., Biffo S.;
RT "The human ITGB4BP gene is constitutively expressed in vitro, but
RT highly modulated in vivo.";
RL Gene 266:35-43(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Umbilical cord blood;
RX PubMed=9653160; DOI=10.1073/pnas.95.14.8175;
RA Mao M., Fu G., Wu J.-S., Zhang Q.-H., Zhou J., Kan L.-X., Huang Q.-H.,
RA He K.-L., Gu B.-W., Han Z.-G., Shen Y., Gu J., Yu Y.-P., Xu S.-H.,
RA Wang Y.-X., Chen S.-J., Chen Z.;
RT "Identification of genes expressed in human CD34(+) hematopoietic
RT stem/progenitor cells by expressed sequence tags and efficient full-
RT length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:8175-8180(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon adenocarcinoma;
RA Shichijo S., Itoh K.;
RT "Identification of immuno-peptidmics that are recognized by tumor-
RT reactive CTL generated from TIL of colon cancer patients.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung, Muscle, and Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10085284; DOI=10.1083/jcb.144.5.823;
RA Sanvito F., Piatti S., Villa A., Bossi M., Lucchini G.,
RA Marchisio P.C., Biffo S.;
RT "The beta4 integrin interactor p27(BBP/eIF6) is an essential nuclear
RT matrix protein involved in 60S ribosomal subunit assembly.";
RL J. Cell Biol. 144:823-837(1999).
RN [12]
RP PHOSPHORYLATION AT SER-174 AND SER-175, SUBCELLULAR LOCATION, AND
RP NUCLEOCYTOPLASMIC SHUTTLING.
RX PubMed=12917340; DOI=10.1128/MCB.23.17.6187-6199.2003;
RA Basu U., Si K., Deng H., Maitra U.;
RT "Phosphorylation of mammalian eukaryotic translation initiation factor
RT 6 and its Saccharomyces cerevisiae homologue Tif6p: evidence that
RT phosphorylation of Tif6p regulates its nucleocytoplasmic distribution
RT and is required for yeast cell growth.";
RL Mol. Cell. Biol. 23:6187-6199(2003).
RN [13]
RP FUNCTION, SUBUNIT, PHOSPHORYLATION AT SER-235, AND INTERACTION WITH
RP GNB2L1.
RX PubMed=14654845; DOI=10.1038/nature02160;
RA Ceci M., Gaviraghi C., Gorrini C., Sala L.A., Offenhauser N.,
RA Marchisio P.C., Biffo S.;
RT "Release of eIF6 (p27BBP) from the 60S subunit allows 80S ribosome
RT assembly.";
RL Nature 426:579-584(2003).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-113, AND MASS
RP SPECTROMETRY.
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239 AND SER-243, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP FUNCTION.
RX PubMed=21536732; DOI=10.1101/gad.623011;
RA Finch A.J., Hilcenko C., Basse N., Drynan L.F., Goyenechea B.,
RA Menne T.F., Gonzalez Fernandez A., Simpson P., D'Santos C.S.,
RA Arends M.J., Donadieu J., Bellanne-Chantelot C., Costanzo M.,
RA Boone C., McKenzie A.N., Freund S.M., Warren A.J.;
RT "Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes
RT Shwachman-Diamond syndrome.";
RL Genes Dev. 25:917-929(2011).
RN [20]
RP PHOSPHORYLATION AT SER-174 AND SER-175 BY CSNK1D/CK1, AND SUBCELLULAR
RP LOCATION.
RX PubMed=21084295; DOI=10.1074/jbc.M110.188565;
RA Biswas A., Mukherjee S., Das S., Shields D., Chow C.W., Maitra U.;
RT "Opposing action of casein kinase 1 and calcineurin in nucleo-
RT cytoplasmic shuttling of mammalian translation initiation factor
RT eIF6.";
RL J. Biol. Chem. 286:3129-3138(2011).
CC -!- FUNCTION: Binds to the 60S ribosomal subunit and prevents its
CC association with the 40S ribosomal subunit to form the 80S
CC initiation complex in the cytoplasm. May behave as a stimulatory
CC translation initiation factor downstream insulin/growth factors.
CC Is also involved in ribosome biogenesis. Associates with pre-60S
CC subunits in the nucleus and is involved in its nuclear export.
CC Cytoplasmic release of TIF6 from 60S subunits and nuclear
CC relocalization is promoted by a RACK1 (GNB2L1)-dependent protein
CC kinase C activity.
CC -!- SUBUNIT: Monomer. Associates with the 60S ribosomal subunit.
CC Interacts with GNB2L1.
CC -!- INTERACTION:
CC Q96C10:DHX58; NbExp=2; IntAct=EBI-372243, EBI-744193;
CC P19525:EIF2AK2; NbExp=2; IntAct=EBI-372243, EBI-640775;
CC Q16612:NREP; NbExp=5; IntAct=EBI-372243, EBI-718657;
CC Q9Y6K5:OAS3; NbExp=2; IntAct=EBI-372243, EBI-6115729;
CC P68404:Prkcb (xeno); NbExp=2; IntAct=EBI-372243, EBI-397048;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus, nucleolus. Note=Shuttles
CC between cytoplasm and nucleus/nucleolus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P56537-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P56537-2; Sequence=VSP_046747;
CC Note=No experimental confirmation available. Gene prediction
CC based on EST data;
CC -!- TISSUE SPECIFICITY: Expressed at very high levels in colon
CC carcinoma with lower levels in normal colon and ileum and lowest
CC levels in kidney and muscle (at protein level).
CC -!- PTM: Phosphorylation at Ser-174 and Ser-175 by CSNK1D/CK1 promotes
CC nuclear export.
CC -!- SIMILARITY: Belongs to the eIF-6 family.
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DR EMBL; AF022229; AAB97735.1; -; mRNA.
DR EMBL; Y11435; CAA72243.1; -; mRNA.
DR EMBL; AF289541; AAK39426.1; -; Genomic_DNA.
DR EMBL; AF289540; AAK39426.1; JOINED; Genomic_DNA.
DR EMBL; AF047433; AAC39897.1; -; mRNA.
DR EMBL; AK314969; BAG37470.1; -; mRNA.
DR EMBL; AB062289; BAB93472.1; -; mRNA.
DR EMBL; CR456764; CAG33045.1; -; mRNA.
DR EMBL; AL121753; CAX12724.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76221.1; -; Genomic_DNA.
DR EMBL; BC001119; AAH01119.1; -; mRNA.
DR EMBL; BC011845; AAH11845.1; -; mRNA.
DR EMBL; BC019305; AAH19305.1; -; mRNA.
DR RefSeq; NP_001254739.1; NM_001267810.1.
DR RefSeq; NP_002203.1; NM_002212.3.
DR RefSeq; NP_852131.1; NM_181466.2.
DR RefSeq; NP_852133.1; NM_181468.2.
DR UniGene; Hs.743992; -.
DR ProteinModelPortal; P56537; -.
DR SMR; P56537; 1-224.
DR IntAct; P56537; 15.
DR MINT; MINT-2804329; -.
DR STRING; 9606.ENSP00000363559; -.
DR Allergome; 8361; Hom s eIF6.
DR PhosphoSite; P56537; -.
DR DMDM; 3122258; -.
DR OGP; P56537; -.
DR REPRODUCTION-2DPAGE; IPI00010105; -.
DR SWISS-2DPAGE; P56537; -.
DR PaxDb; P56537; -.
DR PeptideAtlas; P56537; -.
DR PRIDE; P56537; -.
DR DNASU; 3692; -.
DR Ensembl; ENST00000374436; ENSP00000363559; ENSG00000242372.
DR Ensembl; ENST00000374443; ENSP00000363566; ENSG00000242372.
DR Ensembl; ENST00000374450; ENSP00000363574; ENSG00000242372.
DR GeneID; 3692; -.
DR KEGG; hsa:3692; -.
DR UCSC; uc002xbz.2; human.
DR CTD; 3692; -.
DR GeneCards; GC20M033881; -.
DR HGNC; HGNC:6159; EIF6.
DR HPA; HPA040873; -.
DR MIM; 602912; gene.
DR neXtProt; NX_P56537; -.
DR PharmGKB; PA29958; -.
DR eggNOG; COG1976; -.
DR HOGENOM; HOG000230605; -.
DR HOVERGEN; HBG001300; -.
DR InParanoid; P56537; -.
DR KO; K03264; -.
DR OMA; NDWCAFT; -.
DR PhylomeDB; P56537; -.
DR ChiTaRS; EIF6; human.
DR GeneWiki; EIF6; -.
DR GenomeRNAi; 3692; -.
DR NextBio; 14465; -.
DR PRO; PR:P56537; -.
DR ArrayExpress; P56537; -.
DR Bgee; P56537; -.
DR CleanEx; HS_EIF3A; -.
DR CleanEx; HS_EIF6; -.
DR Genevestigator; P56537; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005638; C:lamin filament; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0043022; F:ribosome binding; IDA:UniProtKB.
DR GO; GO:0003743; F:translation initiation factor activity; IEA:UniProtKB-KW.
DR GO; GO:0042256; P:mature ribosome assembly; IMP:UniProtKB.
DR HAMAP; MF_00032; eIF_6; 1; -.
DR InterPro; IPR002769; eIF6.
DR PANTHER; PTHR10784; PTHR10784; 1.
DR Pfam; PF01912; eIF-6; 1.
DR PIRSF; PIRSF006413; IF-6; 1.
DR SMART; SM00654; eIF6; 1.
DR TIGRFAMs; TIGR00323; eIF-6; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Cytoplasm; Initiation factor;
KW Nucleus; Phosphoprotein; Protein biosynthesis; Reference proteome;
KW Ribosome biogenesis.
FT CHAIN 1 245 Eukaryotic translation initiation factor
FT 6.
FT /FTId=PRO_0000153734.
FT MOD_RES 113 113 Phosphotyrosine.
FT MOD_RES 165 165 Phosphothreonine (By similarity).
FT MOD_RES 166 166 Phosphoserine (By similarity).
FT MOD_RES 174 174 Phosphoserine; by CK1.
FT MOD_RES 175 175 Phosphoserine; by CK1.
FT MOD_RES 235 235 Phosphoserine; by PKC.
FT MOD_RES 239 239 Phosphoserine.
FT MOD_RES 243 243 Phosphoserine.
FT VAR_SEQ 36 123 SVFEGELSDTIPVVHASIAGCRIIGRMCVGNRHGLLVPNNT
FT TDQELQHIRNSLPDTVQIRRVEERLSALGNVTTCNDYVALV
FT HPDLDR -> RCGGSPGAYGGGEACAGVKSSGSGRVPAPLP
FT RHHRVHVPTVCSRASSPIPSPWCTRLSPAAASSGACVW
FT (in isoform 2).
FT /FTId=VSP_046747.
FT CONFLICT 35 36 Missing (in Ref. 3; AAK39426).
SQ SEQUENCE 245 AA; 26599 MW; 5BA97CD5DB0C17C3 CRC64;
MAVRASFENN CEIGCFAKLT NTYCLVAIGG SENFYSVFEG ELSDTIPVVH ASIAGCRIIG
RMCVGNRHGL LVPNNTTDQE LQHIRNSLPD TVQIRRVEER LSALGNVTTC NDYVALVHPD
LDRETEEILA DVLKVEVFRQ TVADQVLVGS YCVFSNQGGL VHPKTSIEDQ DELSSLLQVP
LVAGTVNRGS EVIAAGMVVN DWCAFCGLDT TSTELSVVES VFKLNEAQPS TIATSMRDSL
IDSLT
//
ID IF6_HUMAN Reviewed; 245 AA.
AC P56537; B7ZBG9; Q6IBN8; Q96TD5;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
read moreDT 15-JUL-1998, sequence version 1.
DT 22-JAN-2014, entry version 137.
DE RecName: Full=Eukaryotic translation initiation factor 6;
DE Short=eIF-6;
DE AltName: Full=B(2)GCN homolog;
DE AltName: Full=B4 integrin interactor;
DE AltName: Full=CAB;
DE AltName: Full=p27(BBP);
GN Name=EIF6; Synonyms=EIF3A, ITGB4BP; ORFNames=OK/SW-cl.27;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Skeletal muscle;
RX PubMed=9405604; DOI=10.1073/pnas.94.26.14285;
RA Si K., Chaudhuri J., Chevesich J., Maitra U.;
RT "Molecular cloning and functional expression of a human cDNA encoding
RT translation initiation factor 6.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:14285-14290(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=9374518; DOI=10.1074/jbc.272.48.30314;
RA Biffo S., Sanvito F., Costa S., Preve L., Pignatelli R., Spinardi L.,
RA Marchisio P.C.;
RT "Isolation of a novel beta4 integrin-binding protein (p27(BBP)) highly
RT expressed in epithelial cells.";
RL J. Biol. Chem. 272:30314-30321(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND TISSUE SPECIFICITY.
RX PubMed=11290417; DOI=10.1016/S0378-1119(01)00370-5;
RA Donadini A., Giodini A., Sanvito F., Marchisio P.C., Biffo S.;
RT "The human ITGB4BP gene is constitutively expressed in vitro, but
RT highly modulated in vivo.";
RL Gene 266:35-43(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Umbilical cord blood;
RX PubMed=9653160; DOI=10.1073/pnas.95.14.8175;
RA Mao M., Fu G., Wu J.-S., Zhang Q.-H., Zhou J., Kan L.-X., Huang Q.-H.,
RA He K.-L., Gu B.-W., Han Z.-G., Shen Y., Gu J., Yu Y.-P., Xu S.-H.,
RA Wang Y.-X., Chen S.-J., Chen Z.;
RT "Identification of genes expressed in human CD34(+) hematopoietic
RT stem/progenitor cells by expressed sequence tags and efficient full-
RT length cDNA cloning.";
RL Proc. Natl. Acad. Sci. U.S.A. 95:8175-8180(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Colon adenocarcinoma;
RA Shichijo S., Itoh K.;
RT "Identification of immuno-peptidmics that are recognized by tumor-
RT reactive CTL generated from TIL of colon cancer patients.";
RL Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M.,
RA Beasley O.P., Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J.,
RA Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M.,
RA Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R.,
RA Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M.,
RA Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H.,
RA Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S.,
RA Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E.,
RA Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A.,
RA Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M.,
RA Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A.,
RA Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S.,
RA Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [10]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lung, Muscle, and Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [11]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=10085284; DOI=10.1083/jcb.144.5.823;
RA Sanvito F., Piatti S., Villa A., Bossi M., Lucchini G.,
RA Marchisio P.C., Biffo S.;
RT "The beta4 integrin interactor p27(BBP/eIF6) is an essential nuclear
RT matrix protein involved in 60S ribosomal subunit assembly.";
RL J. Cell Biol. 144:823-837(1999).
RN [12]
RP PHOSPHORYLATION AT SER-174 AND SER-175, SUBCELLULAR LOCATION, AND
RP NUCLEOCYTOPLASMIC SHUTTLING.
RX PubMed=12917340; DOI=10.1128/MCB.23.17.6187-6199.2003;
RA Basu U., Si K., Deng H., Maitra U.;
RT "Phosphorylation of mammalian eukaryotic translation initiation factor
RT 6 and its Saccharomyces cerevisiae homologue Tif6p: evidence that
RT phosphorylation of Tif6p regulates its nucleocytoplasmic distribution
RT and is required for yeast cell growth.";
RL Mol. Cell. Biol. 23:6187-6199(2003).
RN [13]
RP FUNCTION, SUBUNIT, PHOSPHORYLATION AT SER-235, AND INTERACTION WITH
RP GNB2L1.
RX PubMed=14654845; DOI=10.1038/nature02160;
RA Ceci M., Gaviraghi C., Gorrini C., Sala L.A., Offenhauser N.,
RA Marchisio P.C., Biffo S.;
RT "Release of eIF6 (p27BBP) from the 60S subunit allows 80S ribosome
RT assembly.";
RL Nature 426:579-584(2003).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-113, AND MASS
RP SPECTROMETRY.
RX PubMed=15592455; DOI=10.1038/nbt1046;
RA Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,
RA Zha X.-M., Polakiewicz R.D., Comb M.J.;
RT "Immunoaffinity profiling of tyrosine phosphorylation in cancer
RT cells.";
RL Nat. Biotechnol. 23:94-101(2005).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239 AND SER-243, AND
RP MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-239, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [19]
RP FUNCTION.
RX PubMed=21536732; DOI=10.1101/gad.623011;
RA Finch A.J., Hilcenko C., Basse N., Drynan L.F., Goyenechea B.,
RA Menne T.F., Gonzalez Fernandez A., Simpson P., D'Santos C.S.,
RA Arends M.J., Donadieu J., Bellanne-Chantelot C., Costanzo M.,
RA Boone C., McKenzie A.N., Freund S.M., Warren A.J.;
RT "Uncoupling of GTP hydrolysis from eIF6 release on the ribosome causes
RT Shwachman-Diamond syndrome.";
RL Genes Dev. 25:917-929(2011).
RN [20]
RP PHOSPHORYLATION AT SER-174 AND SER-175 BY CSNK1D/CK1, AND SUBCELLULAR
RP LOCATION.
RX PubMed=21084295; DOI=10.1074/jbc.M110.188565;
RA Biswas A., Mukherjee S., Das S., Shields D., Chow C.W., Maitra U.;
RT "Opposing action of casein kinase 1 and calcineurin in nucleo-
RT cytoplasmic shuttling of mammalian translation initiation factor
RT eIF6.";
RL J. Biol. Chem. 286:3129-3138(2011).
CC -!- FUNCTION: Binds to the 60S ribosomal subunit and prevents its
CC association with the 40S ribosomal subunit to form the 80S
CC initiation complex in the cytoplasm. May behave as a stimulatory
CC translation initiation factor downstream insulin/growth factors.
CC Is also involved in ribosome biogenesis. Associates with pre-60S
CC subunits in the nucleus and is involved in its nuclear export.
CC Cytoplasmic release of TIF6 from 60S subunits and nuclear
CC relocalization is promoted by a RACK1 (GNB2L1)-dependent protein
CC kinase C activity.
CC -!- SUBUNIT: Monomer. Associates with the 60S ribosomal subunit.
CC Interacts with GNB2L1.
CC -!- INTERACTION:
CC Q96C10:DHX58; NbExp=2; IntAct=EBI-372243, EBI-744193;
CC P19525:EIF2AK2; NbExp=2; IntAct=EBI-372243, EBI-640775;
CC Q16612:NREP; NbExp=5; IntAct=EBI-372243, EBI-718657;
CC Q9Y6K5:OAS3; NbExp=2; IntAct=EBI-372243, EBI-6115729;
CC P68404:Prkcb (xeno); NbExp=2; IntAct=EBI-372243, EBI-397048;
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus, nucleolus. Note=Shuttles
CC between cytoplasm and nucleus/nucleolus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P56537-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P56537-2; Sequence=VSP_046747;
CC Note=No experimental confirmation available. Gene prediction
CC based on EST data;
CC -!- TISSUE SPECIFICITY: Expressed at very high levels in colon
CC carcinoma with lower levels in normal colon and ileum and lowest
CC levels in kidney and muscle (at protein level).
CC -!- PTM: Phosphorylation at Ser-174 and Ser-175 by CSNK1D/CK1 promotes
CC nuclear export.
CC -!- SIMILARITY: Belongs to the eIF-6 family.
CC -----------------------------------------------------------------------
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DR EMBL; AF022229; AAB97735.1; -; mRNA.
DR EMBL; Y11435; CAA72243.1; -; mRNA.
DR EMBL; AF289541; AAK39426.1; -; Genomic_DNA.
DR EMBL; AF289540; AAK39426.1; JOINED; Genomic_DNA.
DR EMBL; AF047433; AAC39897.1; -; mRNA.
DR EMBL; AK314969; BAG37470.1; -; mRNA.
DR EMBL; AB062289; BAB93472.1; -; mRNA.
DR EMBL; CR456764; CAG33045.1; -; mRNA.
DR EMBL; AL121753; CAX12724.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76221.1; -; Genomic_DNA.
DR EMBL; BC001119; AAH01119.1; -; mRNA.
DR EMBL; BC011845; AAH11845.1; -; mRNA.
DR EMBL; BC019305; AAH19305.1; -; mRNA.
DR RefSeq; NP_001254739.1; NM_001267810.1.
DR RefSeq; NP_002203.1; NM_002212.3.
DR RefSeq; NP_852131.1; NM_181466.2.
DR RefSeq; NP_852133.1; NM_181468.2.
DR UniGene; Hs.743992; -.
DR ProteinModelPortal; P56537; -.
DR SMR; P56537; 1-224.
DR IntAct; P56537; 15.
DR MINT; MINT-2804329; -.
DR STRING; 9606.ENSP00000363559; -.
DR Allergome; 8361; Hom s eIF6.
DR PhosphoSite; P56537; -.
DR DMDM; 3122258; -.
DR OGP; P56537; -.
DR REPRODUCTION-2DPAGE; IPI00010105; -.
DR SWISS-2DPAGE; P56537; -.
DR PaxDb; P56537; -.
DR PeptideAtlas; P56537; -.
DR PRIDE; P56537; -.
DR DNASU; 3692; -.
DR Ensembl; ENST00000374436; ENSP00000363559; ENSG00000242372.
DR Ensembl; ENST00000374443; ENSP00000363566; ENSG00000242372.
DR Ensembl; ENST00000374450; ENSP00000363574; ENSG00000242372.
DR GeneID; 3692; -.
DR KEGG; hsa:3692; -.
DR UCSC; uc002xbz.2; human.
DR CTD; 3692; -.
DR GeneCards; GC20M033881; -.
DR HGNC; HGNC:6159; EIF6.
DR HPA; HPA040873; -.
DR MIM; 602912; gene.
DR neXtProt; NX_P56537; -.
DR PharmGKB; PA29958; -.
DR eggNOG; COG1976; -.
DR HOGENOM; HOG000230605; -.
DR HOVERGEN; HBG001300; -.
DR InParanoid; P56537; -.
DR KO; K03264; -.
DR OMA; NDWCAFT; -.
DR PhylomeDB; P56537; -.
DR ChiTaRS; EIF6; human.
DR GeneWiki; EIF6; -.
DR GenomeRNAi; 3692; -.
DR NextBio; 14465; -.
DR PRO; PR:P56537; -.
DR ArrayExpress; P56537; -.
DR Bgee; P56537; -.
DR CleanEx; HS_EIF3A; -.
DR CleanEx; HS_EIF6; -.
DR Genevestigator; P56537; -.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005638; C:lamin filament; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IDA:HPA.
DR GO; GO:0043022; F:ribosome binding; IDA:UniProtKB.
DR GO; GO:0003743; F:translation initiation factor activity; IEA:UniProtKB-KW.
DR GO; GO:0042256; P:mature ribosome assembly; IMP:UniProtKB.
DR HAMAP; MF_00032; eIF_6; 1; -.
DR InterPro; IPR002769; eIF6.
DR PANTHER; PTHR10784; PTHR10784; 1.
DR Pfam; PF01912; eIF-6; 1.
DR PIRSF; PIRSF006413; IF-6; 1.
DR SMART; SM00654; eIF6; 1.
DR TIGRFAMs; TIGR00323; eIF-6; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Complete proteome; Cytoplasm; Initiation factor;
KW Nucleus; Phosphoprotein; Protein biosynthesis; Reference proteome;
KW Ribosome biogenesis.
FT CHAIN 1 245 Eukaryotic translation initiation factor
FT 6.
FT /FTId=PRO_0000153734.
FT MOD_RES 113 113 Phosphotyrosine.
FT MOD_RES 165 165 Phosphothreonine (By similarity).
FT MOD_RES 166 166 Phosphoserine (By similarity).
FT MOD_RES 174 174 Phosphoserine; by CK1.
FT MOD_RES 175 175 Phosphoserine; by CK1.
FT MOD_RES 235 235 Phosphoserine; by PKC.
FT MOD_RES 239 239 Phosphoserine.
FT MOD_RES 243 243 Phosphoserine.
FT VAR_SEQ 36 123 SVFEGELSDTIPVVHASIAGCRIIGRMCVGNRHGLLVPNNT
FT TDQELQHIRNSLPDTVQIRRVEERLSALGNVTTCNDYVALV
FT HPDLDR -> RCGGSPGAYGGGEACAGVKSSGSGRVPAPLP
FT RHHRVHVPTVCSRASSPIPSPWCTRLSPAAASSGACVW
FT (in isoform 2).
FT /FTId=VSP_046747.
FT CONFLICT 35 36 Missing (in Ref. 3; AAK39426).
SQ SEQUENCE 245 AA; 26599 MW; 5BA97CD5DB0C17C3 CRC64;
MAVRASFENN CEIGCFAKLT NTYCLVAIGG SENFYSVFEG ELSDTIPVVH ASIAGCRIIG
RMCVGNRHGL LVPNNTTDQE LQHIRNSLPD TVQIRRVEER LSALGNVTTC NDYVALVHPD
LDRETEEILA DVLKVEVFRQ TVADQVLVGS YCVFSNQGGL VHPKTSIEDQ DELSSLLQVP
LVAGTVNRGS EVIAAGMVVN DWCAFCGLDT TSTELSVVES VFKLNEAQPS TIATSMRDSL
IDSLT
//
MIM
602912
*RECORD*
*FIELD* NO
602912
*FIELD* TI
*602912 EUKARYOTIC TRANSLATION INITIATION FACTOR 6; EIF6
;;INTEGRIN, BETA-4, BINDING PROTEIN OF; ITGB4BP;;
read morep27, BETA-4 INTEGRIN-BINDING PROTEIN; p27BBP;;
EUKARYOTIC TRANSLATION INITIATION FACTOR 3A; EIF3A
*FIELD* TX
CLONING
The integrin beta-4 subunit (ITGB4; 147557) is highly enriched in
hemidesmosomes, specialized structures providing firm mechanical links
between basal lamina and the intermediate filament cytoskeleton. A
303-amino acid segment of the ITGB4 cytoplasmic domain that encompasses
the first 2 N-terminal fibronectin type III (FNIII) domains and their
interconnecting sequence is necessary for mediating ITGB4 signaling
events and incorporation into hemidesmosomes. Using a yeast 2-hybrid
system to identify polypeptides that interact with this functional
region of the ITGB4 cytodomain, Biffo et al. (1997) isolated human
epithelial cell cDNAs encoding ITGB4-binding protein (ITGB4BP), which
they called p27BBP. Southern blot analysis showed that the human genome
contains a single copy of the ITGB4BP gene. Northern blot analysis and
in situ hybridization detected Itgb4bp mRNA in all mouse tissues
examined, with the highest levels mainly in proliferating epithelia and
in epithelial tissues containing Itgb4. The predicted human ITGB4BP
protein has 245 amino acids and lacks a signal sequence. Western blot
analysis using antibodies against ITGB4BP detected a 27-kD protein in
epithelial cell lysates, which is in agreement with the calculated
molecular mass of ITGB4BP. Both in yeast and in vitro, ITGB4BP
specifically bound to the first 2 FNIII domains of ITGB4. ITGB4BP is an
insoluble protein that is present in the nucleus and cytoplasm. It is
associated with the intermediate filament pool and is localized at the
submembrane level in close apposition with ITGB4. The authors suggested
that ITGB4BP links ITGB4 to the intermediate filament cytoskeleton.
Eukaryotic translation initiation factor-6 (EIF6) binds to the 60S
ribosomal subunit and prevents its association with the 40S ribosomal
subunit. Using antibodies against purified rabbit EIF6 protein to
immunoscreen a HeLa cell cDNA expression library, Si et al. (1997)
isolated a cDNA encoding EIF6. Northern blot analysis detected an
approximately 1.1-kb transcript in all human tissues examined.
GENE FUNCTION
Ceci et al. (2003) demonstrated that the ribosomal 60S subunit is
activated by release of EIF6. In the cytoplasm, EIF6 is bound to free
60S but not to 80S subunits. Furthermore, EIF6 interacts in the
cytoplasm with RACK1 (176981), a receptor for activated protein kinase C
(PKC; see 176960). RACK1 is a major component of translating ribosomes,
which harbor significant amounts of PKC. Loading 60S subunits with EIF6
caused a dose-dependent translational block and impairment of 80S
formation, which were reversed by expression of RACK1 and stimulation of
PKC in vivo and in vitro. PKC stimulation led to EIF6 phosphorylation,
and mutation of a serine residue in the carboxy terminus of EIF6
impaired RACK1/PKC-mediated translational rescue. Ceci et al. (2003)
proposed that EIF6 release regulates subunit joining, and that RACK1
provides a physical and functional link between PKC signaling and
ribosome activation.
To elucidate how microRNAs mediate their repressive effects, Chendrimada
et al. (2007) performed biochemical and functional assays to identify
new factors in the microRNA pathway. Chendrimada et al. (2007) showed
that human RISC (RNA-induced silencing complex) associated with a
multiprotein complex containing MOV10 (610742), the homolog of
Drosophila translational repressor Armitage, and proteins of the 60S
ribosome subunit. Notably, this complex contains the antiassociation
factor EIF6, a ribosome inhibitory protein known to prevent productive
assembly of the 80S ribosome. Depletion of EIF6 in human cells
specifically abrogated miRNA-mediated regulation of target protein and
mRNA levels. Similarly, depletion of EIF6 in C. elegans diminished Lin4
microRNA-mediated repression of the endogenous Lin14 and Lin28 (611043)
target protein and mRNA levels. Chendrimada et al. (2007) concluded that
their results uncovered an evolutionarily conserved function of the
ribosome antiassociation factor EIF6 in microRNA-mediated
posttranscriptional silencing.
Gandin et al. (2008) demonstrated that mammalian eIF6 is required for
efficient initiation of translation in vivo. Eif6-null mouse embryos
were lethal at preimplantation. Heterozygous mice had 50% reduction of
eIF6 levels in all tissues, and showed reduced mass of hepatic and
adipose tissues due to a lower number of cells and to impaired G1/S cell
cycle progression. eIF6 heterozygous cells retained sufficient nucleolar
eIF6 and normal ribosome biogenesis. The liver of eIF6 heterozygous mice
displayed an increase of 80S in polysomal profiles, indicating a defect
in initiation of translation. Consistently, isolated hepatocytes had
impaired insulin-stimulated translation. Heterozygous mouse embryonic
fibroblasts recapitulated the organism phenotype and had normal ribosome
biogenesis, reduced insulin-stimulated translation, and delayed G1/S
phase progression. Furthermore, eIf6 heterozygous cells were resistant
to oncogene-induced transformation. Thus, Gandin et al. (2008) concluded
that eIF6 is the first eIF associated with the large 60S subunit that
regulates translation in response to extracellular signals.
MAPPING
By fluorescence in situ hybridization, Sanvito et al. (1998) mapped the
ITGB4BP gene to 20q11.2.
*FIELD* RF
1. Biffo, S.; Sanvito, F.; Costa, S.; Preve, L.; Pignatelli, R.; Spinardi,
L.; Marchisio, P. C.: Isolation of a novel beta-4 integrin-binding
protein (p27BBP) highly expressed in epithelial cells. J. Biol. Chem. 272:
30314-30321, 1997.
2. Ceci, M.; Gaviraghi, C.; Gorrini, C.; Sala, L. A.; Offenhauser,
N.; Marchisio, P. C.; Biffo, S.: Release of eIF6 (p27-BBP) from the
60S subunit allows 80S ribosome assembly. Nature 426: 579-584, 2003.
3. Chendrimada, T. P.; Finn, K. J.; Ji, X.; Baillat, D.; Gregory,
R. I.; Liebhaber, S. A.; Pasquinelli, A. E.; Shiekhattar, R.: MicroRNA
silencing through RISC recruitment of elF6. Nature 447: 823-828,
2007.
4. Gandin, V.; Miluzio, A.; Barbieri, A. M.; Beugnet, A.; Kiyokawa,
H.; Marchisio, P. C.; Biffo, S.: Eukaryotic initiation factor 6 is
rate-limiting in translation, growth and transformation. Nature 455:
684-688, 2008.
5. Sanvito, F.; Arrigo, G.; Zuffardi, O.; Agnelli, M.; Marchisio,
P. C.; Biffo, S.: Localization of p27 beta-4 binding protein gene
(ITGB4BP) to human chromosome region 20q11.2. Genomics 52: 111-112,
1998.
6. Si, K.; Chaudhuri, J.; Chevesich, J.; Maitra, U.: Molecular cloning
and functional expression of a human cDNA encoding translation initiation
factor 6. Proc. Nat. Acad. Sci. 94: 14285-14290, 1997.
*FIELD* CN
Ada Hamosh - updated: 11/5/2008
Ada Hamosh - updated: 6/29/2007
Ada Hamosh - updated: 12/30/2003
Patti M. Sherman - updated: 12/15/1998
Patti M. Sherman - updated: 12/11/1998
*FIELD* CD
Patti M. Sherman: 8/1/1998
*FIELD* ED
alopez: 11/18/2008
terry: 11/5/2008
mgross: 10/2/2007
alopez: 7/3/2007
terry: 6/29/2007
carol: 6/26/2007
alopez: 12/31/2003
terry: 12/30/2003
carol: 12/15/1998
carol: 12/14/1998
carol: 8/3/1998
terry: 8/3/1998
carol: 8/2/1998
*RECORD*
*FIELD* NO
602912
*FIELD* TI
*602912 EUKARYOTIC TRANSLATION INITIATION FACTOR 6; EIF6
;;INTEGRIN, BETA-4, BINDING PROTEIN OF; ITGB4BP;;
read morep27, BETA-4 INTEGRIN-BINDING PROTEIN; p27BBP;;
EUKARYOTIC TRANSLATION INITIATION FACTOR 3A; EIF3A
*FIELD* TX
CLONING
The integrin beta-4 subunit (ITGB4; 147557) is highly enriched in
hemidesmosomes, specialized structures providing firm mechanical links
between basal lamina and the intermediate filament cytoskeleton. A
303-amino acid segment of the ITGB4 cytoplasmic domain that encompasses
the first 2 N-terminal fibronectin type III (FNIII) domains and their
interconnecting sequence is necessary for mediating ITGB4 signaling
events and incorporation into hemidesmosomes. Using a yeast 2-hybrid
system to identify polypeptides that interact with this functional
region of the ITGB4 cytodomain, Biffo et al. (1997) isolated human
epithelial cell cDNAs encoding ITGB4-binding protein (ITGB4BP), which
they called p27BBP. Southern blot analysis showed that the human genome
contains a single copy of the ITGB4BP gene. Northern blot analysis and
in situ hybridization detected Itgb4bp mRNA in all mouse tissues
examined, with the highest levels mainly in proliferating epithelia and
in epithelial tissues containing Itgb4. The predicted human ITGB4BP
protein has 245 amino acids and lacks a signal sequence. Western blot
analysis using antibodies against ITGB4BP detected a 27-kD protein in
epithelial cell lysates, which is in agreement with the calculated
molecular mass of ITGB4BP. Both in yeast and in vitro, ITGB4BP
specifically bound to the first 2 FNIII domains of ITGB4. ITGB4BP is an
insoluble protein that is present in the nucleus and cytoplasm. It is
associated with the intermediate filament pool and is localized at the
submembrane level in close apposition with ITGB4. The authors suggested
that ITGB4BP links ITGB4 to the intermediate filament cytoskeleton.
Eukaryotic translation initiation factor-6 (EIF6) binds to the 60S
ribosomal subunit and prevents its association with the 40S ribosomal
subunit. Using antibodies against purified rabbit EIF6 protein to
immunoscreen a HeLa cell cDNA expression library, Si et al. (1997)
isolated a cDNA encoding EIF6. Northern blot analysis detected an
approximately 1.1-kb transcript in all human tissues examined.
GENE FUNCTION
Ceci et al. (2003) demonstrated that the ribosomal 60S subunit is
activated by release of EIF6. In the cytoplasm, EIF6 is bound to free
60S but not to 80S subunits. Furthermore, EIF6 interacts in the
cytoplasm with RACK1 (176981), a receptor for activated protein kinase C
(PKC; see 176960). RACK1 is a major component of translating ribosomes,
which harbor significant amounts of PKC. Loading 60S subunits with EIF6
caused a dose-dependent translational block and impairment of 80S
formation, which were reversed by expression of RACK1 and stimulation of
PKC in vivo and in vitro. PKC stimulation led to EIF6 phosphorylation,
and mutation of a serine residue in the carboxy terminus of EIF6
impaired RACK1/PKC-mediated translational rescue. Ceci et al. (2003)
proposed that EIF6 release regulates subunit joining, and that RACK1
provides a physical and functional link between PKC signaling and
ribosome activation.
To elucidate how microRNAs mediate their repressive effects, Chendrimada
et al. (2007) performed biochemical and functional assays to identify
new factors in the microRNA pathway. Chendrimada et al. (2007) showed
that human RISC (RNA-induced silencing complex) associated with a
multiprotein complex containing MOV10 (610742), the homolog of
Drosophila translational repressor Armitage, and proteins of the 60S
ribosome subunit. Notably, this complex contains the antiassociation
factor EIF6, a ribosome inhibitory protein known to prevent productive
assembly of the 80S ribosome. Depletion of EIF6 in human cells
specifically abrogated miRNA-mediated regulation of target protein and
mRNA levels. Similarly, depletion of EIF6 in C. elegans diminished Lin4
microRNA-mediated repression of the endogenous Lin14 and Lin28 (611043)
target protein and mRNA levels. Chendrimada et al. (2007) concluded that
their results uncovered an evolutionarily conserved function of the
ribosome antiassociation factor EIF6 in microRNA-mediated
posttranscriptional silencing.
Gandin et al. (2008) demonstrated that mammalian eIF6 is required for
efficient initiation of translation in vivo. Eif6-null mouse embryos
were lethal at preimplantation. Heterozygous mice had 50% reduction of
eIF6 levels in all tissues, and showed reduced mass of hepatic and
adipose tissues due to a lower number of cells and to impaired G1/S cell
cycle progression. eIF6 heterozygous cells retained sufficient nucleolar
eIF6 and normal ribosome biogenesis. The liver of eIF6 heterozygous mice
displayed an increase of 80S in polysomal profiles, indicating a defect
in initiation of translation. Consistently, isolated hepatocytes had
impaired insulin-stimulated translation. Heterozygous mouse embryonic
fibroblasts recapitulated the organism phenotype and had normal ribosome
biogenesis, reduced insulin-stimulated translation, and delayed G1/S
phase progression. Furthermore, eIf6 heterozygous cells were resistant
to oncogene-induced transformation. Thus, Gandin et al. (2008) concluded
that eIF6 is the first eIF associated with the large 60S subunit that
regulates translation in response to extracellular signals.
MAPPING
By fluorescence in situ hybridization, Sanvito et al. (1998) mapped the
ITGB4BP gene to 20q11.2.
*FIELD* RF
1. Biffo, S.; Sanvito, F.; Costa, S.; Preve, L.; Pignatelli, R.; Spinardi,
L.; Marchisio, P. C.: Isolation of a novel beta-4 integrin-binding
protein (p27BBP) highly expressed in epithelial cells. J. Biol. Chem. 272:
30314-30321, 1997.
2. Ceci, M.; Gaviraghi, C.; Gorrini, C.; Sala, L. A.; Offenhauser,
N.; Marchisio, P. C.; Biffo, S.: Release of eIF6 (p27-BBP) from the
60S subunit allows 80S ribosome assembly. Nature 426: 579-584, 2003.
3. Chendrimada, T. P.; Finn, K. J.; Ji, X.; Baillat, D.; Gregory,
R. I.; Liebhaber, S. A.; Pasquinelli, A. E.; Shiekhattar, R.: MicroRNA
silencing through RISC recruitment of elF6. Nature 447: 823-828,
2007.
4. Gandin, V.; Miluzio, A.; Barbieri, A. M.; Beugnet, A.; Kiyokawa,
H.; Marchisio, P. C.; Biffo, S.: Eukaryotic initiation factor 6 is
rate-limiting in translation, growth and transformation. Nature 455:
684-688, 2008.
5. Sanvito, F.; Arrigo, G.; Zuffardi, O.; Agnelli, M.; Marchisio,
P. C.; Biffo, S.: Localization of p27 beta-4 binding protein gene
(ITGB4BP) to human chromosome region 20q11.2. Genomics 52: 111-112,
1998.
6. Si, K.; Chaudhuri, J.; Chevesich, J.; Maitra, U.: Molecular cloning
and functional expression of a human cDNA encoding translation initiation
factor 6. Proc. Nat. Acad. Sci. 94: 14285-14290, 1997.
*FIELD* CN
Ada Hamosh - updated: 11/5/2008
Ada Hamosh - updated: 6/29/2007
Ada Hamosh - updated: 12/30/2003
Patti M. Sherman - updated: 12/15/1998
Patti M. Sherman - updated: 12/11/1998
*FIELD* CD
Patti M. Sherman: 8/1/1998
*FIELD* ED
alopez: 11/18/2008
terry: 11/5/2008
mgross: 10/2/2007
alopez: 7/3/2007
terry: 6/29/2007
carol: 6/26/2007
alopez: 12/31/2003
terry: 12/30/2003
carol: 12/15/1998
carol: 12/14/1998
carol: 8/3/1998
terry: 8/3/1998
carol: 8/2/1998