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Protein

Eukaryotic translation initiation factor 6

Gene

EIF6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Complete GO annotation...

Keywords - Molecular functioni

Initiation factor

Keywords - Biological processi

Protein biosynthesis, Ribosome biogenesis

Enzyme and pathway databases

BioCyciZFISH:ENSG00000126005-MONOMER.
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

HGNCiHGNC:6159. EIF6.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: GO_Central
  • extracellular exosome Source: UniProtKB
  • nucleolus Source: GO_Central
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • preribosome, large subunit precursor Source: GO_Central
Complete GO annotation...

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-2DPAGEIPI00010105.
SWISS-2DPAGEP56537.

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

WithEntry#Exp.IntActNotes
DHX58Q96C102EBI-372243,EBI-744193
EIF2AK2P195252EBI-372243,EBI-640775
NREPQ166125EBI-372243,EBI-718657
OAS3Q9Y6K52EBI-372243,EBI-6115729
PrkcbP684042EBI-372243,EBI-397048From a different organism.

Protein-protein interaction databases

BioGridi109898. 143 interactors.
IntActiP56537. 23 interactors.
MINTiMINT-2804329.
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.
InterProiIPR002769. eIF6.
[Graphical view]
PANTHERiPTHR10784. PTHR10784. 1 hit.
PfamiPF01912. eIF-6. 1 hit.
[Graphical view]
PIRSFiPIRSF006413. IF-6. 1 hit.
SMARTiSM00654. eIF6. 1 hit.
[Graphical view]
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. Translation: CAX12724.1.
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

Cross-referencesi

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. Translation: CAX12724.1.
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.

3D structure databases

ProteinModelPortaliP56537.
SMRiP56537.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi109898. 143 interactors.
IntActiP56537. 23 interactors.
MINTiMINT-2804329.
STRINGi9606.ENSP00000363559.

Protein family/group databases

Allergomei8361. Hom s eIF6.

PTM databases

iPTMnetiP56537.
PhosphoSitePlusiP56537.
SwissPalmiP56537.

Polymorphism and mutation databases

BioMutaiEIF6.

2D gel databases

OGPiP56537.
REPRODUCTION-2DPAGEIPI00010105.
SWISS-2DPAGEP56537.

Proteomic databases

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

Protocols and materials databases

DNASUi3692.
Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi3692.
DisGeNETi3692.
GeneCardsiEIF6.
HGNCiHGNC:6159. EIF6.
HPAiHPA040873.
MIMi602912. gene.
neXtProtiNX_P56537.
OpenTargetsiENSG00000242372.
PharmGKBiPA29958.
GenAtlasiSearch...

Phylogenomic databases

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

Enzyme and pathway databases

BioCyciZFISH:ENSG00000126005-MONOMER.
SIGNORiP56537.

Miscellaneous databases

ChiTaRSiEIF6. human.
GeneWikiiEIF6.
GenomeRNAii3692.
PROiP56537.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000242372.
CleanExiHS_EIF3A.
HS_EIF6.
ExpressionAtlasiP56537. baseline and differential.
GenevisibleiP56537. HS.

Family and domain databases

CDDicd00527. IF6. 1 hit.
HAMAPiMF_00032. eIF_6. 1 hit.
InterProiIPR002769. eIF6.
[Graphical view]
PANTHERiPTHR10784. PTHR10784. 1 hit.
PfamiPF01912. eIF-6. 1 hit.
[Graphical view]
PIRSFiPIRSF006413. IF-6. 1 hit.
SMARTiSM00654. eIF6. 1 hit.
[Graphical view]
TIGRFAMsiTIGR00323. eIF-6. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiIF6_HUMAN
AccessioniPrimary (citable) accession number: P56537
Secondary accession number(s): B7ZBG9, Q6IBN8, Q96TD5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: July 15, 1998
Last modified: November 30, 2016
This is version 168 of the entry and version 1 of the sequence. [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

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Translation initiation factors
    List of translation initiation factor entries
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.