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Protein

Eukaryotic translation initiation factor 6

Gene

EIF6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Binds to the 60S ribosomal subunit and prevents its association with the 40S ribosomal subunit to form the 80S initiation complex in the cytoplasm. Behaves 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 (RACK1)-dependent protein kinase C activity (PubMed:10085284, PubMed:14654845, PubMed:21536732). In tissues responsive to insulin, controls fatty acid synthesis and glycolysis by exerting translational control of adipogenic transcription factors such as CEBPB, CEBPD and ATF4 that have G/C rich or uORF in their 5'UTR. Required for ROS-dependent megakaryocyte maturation and platelets formation, controls the expression of mitochondrial respiratory chain genes involved in reactive oxygen species (ROS) synthesis (By similarity). Involved in miRNA-mediated gene silencing by the RNA-induced silencing complex (RISC). Required for both miRNA-mediated translational repression and miRNA-mediated cleavage of complementary mRNAs by RISC (PubMed:17507929). Modulates cell cycle progression and global translation of pre-B cells, its activation seems to be rate-limiting in tumorigenesis and tumor growth (By similarity).UniRule annotation4 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionInitiation factor
Biological processProtein biosynthesis, Ribosome biogenesis

Enzyme and pathway databases

SIGNORiP56537

Names & Taxonomyi

Protein namesi
Recommended name:
Eukaryotic translation initiation factor 6UniRule annotation
Short name:
eIF-6UniRule annotation
Alternative name(s):
B(2)GCN homolog
B4 integrin interactor
CAB
p27(BBP)
Gene namesi
Name:EIF6UniRule annotationImported
Synonyms:EIF3A, ITGB4BPUniRule annotation
ORF Names:OK/SW-cl.27
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

EuPathDBiHostDB:ENSG00000242372.6
HGNCiHGNC:6159 EIF6
MIMi602912 gene
neXtProtiNX_P56537

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi3692
OpenTargetsiENSG00000242372
PharmGKBiPA29958

Protein family/group databases

Allergomei8361 Hom s eIF6

Polymorphism and mutation databases

BioMutaiEIF6

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001537341 – 245Eukaryotic translation initiation factor 6Add BLAST245

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei113PhosphotyrosineCombined sources1
Modified residuei165PhosphothreonineUniRule annotationBy similarity1
Modified residuei166PhosphoserineUniRule annotationBy similarity1
Modified residuei174Phosphoserine; by CK1UniRule annotation2 Publications1
Modified residuei175Phosphoserine; by CK1UniRule annotation2 Publications1
Modified residuei235Phosphoserine; by PKCUniRule annotation1 Publication1
Modified residuei239PhosphoserineCombined sources1
Modified residuei243PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylation at Ser-174 and Ser-175 by CSNK1D/CK1 promotes nuclear export.3 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP56537
MaxQBiP56537
PaxDbiP56537
PeptideAtlasiP56537
PRIDEiP56537
TopDownProteomicsiP56537-1 [P56537-1]

2D gel databases

OGPiP56537
REPRODUCTION-2DPAGEiIPI00010105
SWISS-2DPAGEiP56537

PTM databases

iPTMnetiP56537
PhosphoSitePlusiP56537
SwissPalmiP56537

Expressioni

Tissue specificityi

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).1 Publication

Gene expression databases

BgeeiENSG00000242372
CleanExiHS_EIF3A
HS_EIF6
ExpressionAtlasiP56537 baseline and differential
GenevisibleiP56537 HS

Organism-specific databases

HPAiHPA040873

Interactioni

Subunit structurei

Monomer. Associates with the 60S ribosomal subunit. Interacts with RACK1. Interacts with DICER1, AGO2, TARBP2, MOV10 and RPL7A; they form a large RNA-induced silencing complex (RISC) (PubMed:17507929).UniRule annotation2 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi109898, 147 interactors
CORUMiP56537
IntActiP56537, 99 interactors
MINTiP56537
STRINGi9606.ENSP00000363559

Structurei

3D structure databases

ProteinModelPortaliP56537
SMRiP56537
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the eIF-6 family.UniRule annotation

Phylogenomic databases

eggNOGiKOG3185 Eukaryota
COG1976 LUCA
GeneTreeiENSGT00390000015972
HOGENOMiHOG000230605
HOVERGENiHBG001300
InParanoidiP56537
KOiK03264
OMAiNDWCAFT
OrthoDBiEOG091G0HYF
PhylomeDBiP56537
TreeFamiTF105396

Family and domain databases

CDDicd00527 IF6, 1 hit
HAMAPiMF_00032 eIF_6, 1 hit
InterProiView protein in InterPro
IPR002769 eIF6
PANTHERiPTHR10784 PTHR10784, 1 hit
PfamiView protein in Pfam
PF01912 eIF-6, 1 hit
PIRSFiPIRSF006413 IF-6, 1 hit
SMARTiView protein in SMART
SM00654 eIF6, 1 hit
TIGRFAMsiTIGR00323 eIF-6, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P56537-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAVRASFENN CEIGCFAKLT NTYCLVAIGG SENFYSVFEG ELSDTIPVVH
60 70 80 90 100
ASIAGCRIIG RMCVGNRHGL LVPNNTTDQE LQHIRNSLPD TVQIRRVEER
110 120 130 140 150
LSALGNVTTC NDYVALVHPD LDRETEEILA DVLKVEVFRQ TVADQVLVGS
160 170 180 190 200
YCVFSNQGGL VHPKTSIEDQ DELSSLLQVP LVAGTVNRGS EVIAAGMVVN
210 220 230 240
DWCAFCGLDT TSTELSVVES VFKLNEAQPS TIATSMRDSL IDSLT
Length:245
Mass (Da):26,599
Last modified:July 15, 1998 - v1
Checksum:i5BA97CD5DB0C17C3
GO
Isoform 2 (identifier: P56537-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     36-123: SVFEGELSDT...VALVHPDLDR → RCGGSPGAYG...AAASSGACVW

Note: No experimental confirmation available. Gene prediction based on EST data.
Show »
Length:226
Mass (Da):23,735
Checksum:iA14404615A3FE42B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti35 – 36Missing in AAK39426 (PubMed:11290417).Curated2

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04674736 – 123SVFEG…PDLDR → RCGGSPGAYGGGEACAGVKS SGSGRVPAPLPRHHRVHVPT VCSRASSPIPSPWCTRLSPA AASSGACVW in isoform 2. CuratedAdd BLAST88

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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 No translation available.
CH471077 Genomic DNA Translation: EAW76221.1
BC001119 mRNA Translation: AAH01119.1
BC011845 mRNA Translation: AAH11845.1
BC019305 mRNA Translation: AAH19305.1
CCDSiCCDS13249.1 [P56537-1]
CCDS13250.1 [P56537-2]
RefSeqiNP_001254739.1, NM_001267810.1 [P56537-1]
NP_002203.1, NM_002212.3 [P56537-1]
NP_852131.1, NM_181466.2 [P56537-2]
NP_852133.1, NM_181468.2 [P56537-1]
UniGeneiHs.743992

Genome annotation databases

EnsembliENST00000374436; ENSP00000363559; ENSG00000242372 [P56537-1]
ENST00000374443; ENSP00000363566; ENSG00000242372 [P56537-2]
ENST00000374450; ENSP00000363574; ENSG00000242372 [P56537-1]
ENST00000621148; ENSP00000483289; ENSG00000242372 [P56537-1]
GeneIDi3692
KEGGihsa:3692
UCSCiuc002xbv.3 human [P56537-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiIF6_HUMAN
AccessioniPrimary (citable) accession number: P56537
Secondary accession number(s): B7ZBG9, Q6IBN8, Q96TD5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 15, 1998
Last modified: April 25, 2018
This is version 178 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health