IF6_MOUSE
ID IF6_MOUSE Reviewed; 245 AA.
AC O55135;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 30-MAY-2000, sequence version 2.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Eukaryotic translation initiation factor 6 {ECO:0000255|HAMAP-Rule:MF_03132};
DE Short=eIF-6 {ECO:0000255|HAMAP-Rule:MF_03132};
DE AltName: Full=B4 integrin interactor;
DE AltName: Full=CAB;
DE AltName: Full=p27(BBP);
GN Name=Eif6; Synonyms=Itgb4bp;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ; TISSUE=Liver;
RX PubMed=10206977; DOI=10.1074/jbc.274.17.11653;
RA Wood L.C., Ashby M.N., Grunfeld C., Feingold K.R.;
RT "Cloning of murine translation initiation factor 6 and functional analysis
RT of the homologous sequence YPR016c in Saccharomyces cerevisiae.";
RL J. Biol. Chem. 274:11653-11659(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon, and Kidney;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 80-163.
RC STRAIN=BALB/cJ;
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 [4]
RP SUBCELLULAR LOCATION, 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 highly
RT modulated in vivo.";
RL Gene 266:35-43(2001).
RN [5]
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP SER-235.
RX PubMed=18784653; DOI=10.1038/nature07267;
RA Gandin V., Miluzio A., Barbieri A.M., Beugnet A., Kiyokawa H.,
RA Marchisio P.C., Biffo S.;
RT "Eukaryotic initiation factor 6 is rate-limiting in translation, growth and
RT transformation.";
RL Nature 455:684-688(2008).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Pancreas,
RC Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [7]
RP FUNCTION, PHOSPHORYLATION AT SER-235, AND MUTAGENESIS OF SER-235.
RX PubMed=21665150; DOI=10.1016/j.ccr.2011.04.018;
RA Miluzio A., Beugnet A., Grosso S., Brina D., Mancino M., Campaner S.,
RA Amati B., de Marco A., Biffo S.;
RT "Impairment of cytoplasmic eIF6 activity restricts lymphomagenesis and
RT tumor progression without affecting normal growth.";
RL Cancer Cell 19:765-775(2011).
RN [8]
RP PHOSPHORYLATION AT THR-165; SER-166; SER-174 AND SER-175, IDENTIFICATION AT
RP THE 60S RIBOSOME SUBUNIT, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=21536732; DOI=10.1101/gad.623011;
RA Finch A.J., Hilcenko C., Basse N., Drynan L.F., Goyenechea B., Menne T.F.,
RA Gonzalez Fernandez A., Simpson P., D'Santos C.S., Arends M.J., Donadieu J.,
RA Bellanne-Chantelot C., Costanzo M., Boone C., McKenzie A.N., Freund S.M.,
RA 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 [9]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=26391622; DOI=10.1111/jth.13150;
RA Ricciardi S., Miluzio A., Brina D., Clarke K., Bonomo M., Aiolfi R.,
RA Guidotti L.G., Falciani F., Biffo S.;
RT "Eukaryotic translation initiation factor 6 is a novel regulator of
RT reactive oxygen species-dependent megakaryocyte maturation.";
RL J. Thromb. Haemost. 13:2108-2118(2015).
RN [10]
RP FUNCTION, TISSUE SPECIFICITY, AND MUTAGENESIS OF SER-235.
RX PubMed=26383020; DOI=10.1038/ncomms9261;
RA Brina D., Miluzio A., Ricciardi S., Clarke K., Davidsen P.K., Viero G.,
RA Tebaldi T., Offenhaeuser N., Rozman J., Rathkolb B., Neschen S.,
RA Klingenspor M., Wolf E., Gailus-Durner V., Fuchs H., Hrabe de Angelis M.,
RA Quattrone A., Falciani F., Biffo S.;
RT "eIF6 coordinates insulin sensitivity and lipid metabolism by coupling
RT translation to transcription.";
RL Nat. Commun. 6:8261-8261(2015).
RN [11]
RP UFMYLATION.
RX PubMed=28575669; DOI=10.1016/j.cell.2017.05.022;
RA Simsek D., Tiu G.C., Flynn R.A., Byeon G.W., Leppek K., Xu A.F.,
RA Chang H.Y., Barna M.;
RT "The mammalian ribo-interactome reveals ribosome functional diversity and
RT heterogeneity.";
RL Cell 169:1051-1065(2017).
CC -!- FUNCTION: Binds to the 60S ribosomal subunit and prevents its
CC association with the 40S ribosomal subunit to form the 80S initiation
CC complex in the cytoplasm. Behaves as a stimulatory translation
CC initiation factor downstream insulin/growth factors. Is also involved
CC in ribosome biogenesis. Associates with pre-60S subunits in the nucleus
CC and is involved in its nuclear export. Cytoplasmic release of TIF6 from
CC 60S subunits and nuclear relocalization is promoted by a RACK1 (RACK1)-
CC dependent protein kinase C activity. In tissues responsive to insulin,
CC controls fatty acid synthesis and glycolysis by exerting translational
CC control of adipogenic transcription factors such as CEBPB, CEBPD and
CC ATF4 that have G/C rich or uORF in their 5'UTR (PubMed:26383020).
CC Required for ROS-dependent megakaryocyte maturation and platelets
CC formation, controls the expression of mitochondrial respiratory chain
CC genes involved in reactive oxygen species (ROS) synthesis
CC (PubMed:26391622). Involved in miRNA-mediated gene silencing by the
CC RNA-induced silencing complex (RISC). Required for both miRNA-mediated
CC translational repression and miRNA-mediated cleavage of complementary
CC mRNAs by RISC (By similarity). Modulates cell cycle progression and
CC global translation of pre-B cells, its activation seems to be rate-
CC limiting in tumorigenesis and tumor growth (PubMed:21665150).
CC {ECO:0000255|HAMAP-Rule:MF_03132, ECO:0000269|PubMed:18784653,
CC ECO:0000269|PubMed:21665150, ECO:0000269|PubMed:26383020,
CC ECO:0000269|PubMed:26391622}.
CC -!- SUBUNIT: Monomer. Associates with the 60S ribosomal subunit. Interacts
CC with RACK1. Interacts with DICER1, AGO2, TARBP2, MOV10 and RPL7A; they
CC form a large RNA-induced silencing complex (RISC). {ECO:0000255|HAMAP-
CC Rule:MF_03132}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus, nucleolus. Note=Shuttles
CC between cytoplasm and nucleus/nucleolus.
CC -!- TISSUE SPECIFICITY: Detected in bladder, duodenum, liver, esophagus,
CC pancreas, adipose tissue, megakaryocytes and testis with lower levels
CC in muscle (at protein level). {ECO:0000269|PubMed:11290417,
CC ECO:0000269|PubMed:26383020, ECO:0000269|PubMed:26391622}.
CC -!- PTM: Phosphorylation at Ser-174 and Ser-175 by CSNK1D/CK1 promotes
CC nuclear export. {ECO:0000250|UniProtKB:P56537}.
CC -!- PTM: Ufmylated by UFL1. {ECO:0000269|PubMed:28575669}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethality. Embryos die at
CC preimplantation stage. {ECO:0000269|PubMed:18784653}.
CC -!- SIMILARITY: Belongs to the eIF-6 family. {ECO:0000255|HAMAP-
CC Rule:MF_03132}.
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DR EMBL; AF047046; AAD28078.1; -; mRNA.
DR EMBL; BC015274; AAH15274.1; -; mRNA.
DR EMBL; BC024442; AAH24442.1; -; mRNA.
DR EMBL; Y11460; CAA72246.1; -; mRNA.
DR CCDS; CCDS16956.1; -.
DR RefSeq; NP_034709.1; NM_010579.2.
DR AlphaFoldDB; O55135; -.
DR SMR; O55135; -.
DR BioGRID; 200831; 32.
DR IntAct; O55135; 4.
DR STRING; 10090.ENSMUSP00000029142; -.
DR iPTMnet; O55135; -.
DR PhosphoSitePlus; O55135; -.
DR SwissPalm; O55135; -.
DR EPD; O55135; -.
DR jPOST; O55135; -.
DR PaxDb; O55135; -.
DR PeptideAtlas; O55135; -.
DR PRIDE; O55135; -.
DR ProteomicsDB; 273095; -.
DR Antibodypedia; 35156; 266 antibodies from 35 providers.
DR DNASU; 16418; -.
DR Ensembl; ENSMUST00000029142; ENSMUSP00000029142; ENSMUSG00000027613.
DR GeneID; 16418; -.
DR KEGG; mmu:16418; -.
DR UCSC; uc008nll.1; mouse.
DR CTD; 3692; -.
DR MGI; MGI:1196288; Eif6.
DR VEuPathDB; HostDB:ENSMUSG00000027613; -.
DR eggNOG; KOG3185; Eukaryota.
DR GeneTree; ENSGT00390000015972; -.
DR HOGENOM; CLU_071894_0_0_1; -.
DR InParanoid; O55135; -.
DR OMA; GEDTTGP; -.
DR OrthoDB; 1157302at2759; -.
DR PhylomeDB; O55135; -.
DR TreeFam; TF105396; -.
DR BioGRID-ORCS; 16418; 34 hits in 78 CRISPR screens.
DR PRO; PR:O55135; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; O55135; protein.
DR Bgee; ENSMUSG00000027613; Expressed in small intestine Peyer's patch and 259 other tissues.
DR ExpressionAtlas; O55135; baseline and differential.
DR Genevisible; O55135; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005882; C:intermediate filament; IDA:MGI.
DR GO; GO:0005638; C:lamin filament; IDA:MGI.
DR GO; GO:0005730; C:nucleolus; IBA:GO_Central.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0030687; C:preribosome, large subunit precursor; IBA:GO_Central.
DR GO; GO:0043023; F:ribosomal large subunit binding; IBA:GO_Central.
DR GO; GO:0043022; F:ribosome binding; ISS:UniProtKB.
DR GO; GO:0003743; F:translation initiation factor activity; IEA:UniProtKB-UniRule.
DR GO; GO:1902626; P:assembly of large subunit precursor of preribosome; IBA:GO_Central.
DR GO; GO:0000460; P:maturation of 5.8S rRNA; IBA:GO_Central.
DR GO; GO:0000470; P:maturation of LSU-rRNA; IBA:GO_Central.
DR GO; GO:0042256; P:mature ribosome assembly; ISS:UniProtKB.
DR GO; GO:0035195; P:miRNA-mediated gene silencing; ISS:UniProtKB.
DR GO; GO:0035278; P:miRNA-mediated gene silencing by inhibition of translation; ISS:UniProtKB.
DR GO; GO:0045727; P:positive regulation of translation; IMP:UniProtKB.
DR GO; GO:0042304; P:regulation of fatty acid biosynthetic process; IMP:UniProtKB.
DR GO; GO:0006110; P:regulation of glycolytic process; IMP:UniProtKB.
DR GO; GO:0045652; P:regulation of megakaryocyte differentiation; IMP:UniProtKB.
DR GO; GO:2000377; P:regulation of reactive oxygen species metabolic process; IMP:UniProtKB.
DR GO; GO:0032868; P:response to insulin; IMP:UniProtKB.
DR GO; GO:0000054; P:ribosomal subunit export from nucleus; IBA:GO_Central.
DR CDD; cd00527; IF6; 1.
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 Cytoplasm; Initiation factor; Nucleus; Phosphoprotein;
KW Protein biosynthesis; Reference proteome; Ribosome biogenesis;
KW Ubl conjugation.
FT CHAIN 1..245
FT /note="Eukaryotic translation initiation factor 6"
FT /id="PRO_0000153735"
FT MOD_RES 113
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P56537"
FT MOD_RES 165
FT /note="Phosphothreonine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03132,
FT ECO:0000269|PubMed:21536732"
FT MOD_RES 166
FT /note="Phosphoserine"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03132,
FT ECO:0000269|PubMed:21536732"
FT MOD_RES 174
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03132,
FT ECO:0000269|PubMed:21536732"
FT MOD_RES 175
FT /note="Phosphoserine; by CK1"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03132,
FT ECO:0000269|PubMed:21536732"
FT MOD_RES 235
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03132,
FT ECO:0000269|PubMed:21665150"
FT MOD_RES 239
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P56537, ECO:0000255|HAMAP-
FT Rule:MF_03132"
FT MOD_RES 243
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P56537, ECO:0000255|HAMAP-
FT Rule:MF_03132"
FT MUTAGEN 235
FT /note="S->A: Abolishes insulin-stimulated translation,
FT abrogates tumorigenesis."
FT /evidence="ECO:0000269|PubMed:18784653,
FT ECO:0000269|PubMed:21665150, ECO:0000269|PubMed:26383020"
SQ SEQUENCE 245 AA; 26511 MW; 35BF0F4C17D5E045 CRC64;
MAVRASFENN CEVGCFAKLT NAYCLVAIGG SENFYSVFEG ELSDAIPVVH ASIAGCRIIG
RMCVGNRHGL LVPNNTTDQE LQHIRNSLPD SVQIRRVEER LSALGNVTTC NDYVALVHPD
LDRETEEILA DVLKVEVFRQ TVADQVLVGS YCVFSNQGGL VHPKTSIEDQ DELSSLLQVP
LVAGTVNRGS EVIAAGMVVN DWCAFCGLDT TSTELSVVES VFKLNEAKPS TIATSMRDSL
IDSLT
