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UniProtKB - O15371 (EIF3D_HUMAN)

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Protein

Eukaryotic translation initiation factor 3 subunit D

Gene

EIF3D

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

Functioni

mRNA cap-binding component of the eukaryotic translation initiation factor 3 (eIF-3) complex, a complex required for several steps in the initiation of protein synthesis of a specialized repertoire of mRNAs (PubMed:27462815). The eIF-3 complex associates with the 40S ribosome and facilitates the recruitment of eIF-1, eIF-1A, eIF-2:GTP:methionyl-tRNAi and eIF-5 to form the 43S pre-initiation complex (43S PIC). The eIF-3 complex stimulates mRNA recruitment to the 43S PIC and scanning of the mRNA for AUG recognition. The eIF-3 complex is also required for disassembly and recycling of post-termination ribosomal complexes and subsequently prevents premature joining of the 40S and 60S ribosomal subunits prior to initiation (PubMed:18599441, PubMed:25849773). The eIF-3 complex specifically targets and initiates translation of a subset of mRNAs involved in cell proliferation, including cell cycling, differentiation and apoptosis, and uses different modes of RNA stem-loop binding to exert either translational activation or repression (PubMed:25849773). In the eIF-3 complex, EIF3D specifically recognizes and binds the 7-methylguanosine cap of a subset of mRNAs (PubMed:27462815).3 Publications
(Microbial infection) In case of FCV infection, plays a role in the ribosomal termination-reinitiation event leading to the translation of VP2 (PubMed:18056426).1 Publication

GO - Molecular functioni

  • mRNA cap binding Source: UniProtKB
  • RNA binding Source: UniProtKB
  • translation initiation factor activity Source: UniProtKB-KW
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • cap-dependent translational initiation Source: UniProtKB
  • formation of cytoplasmic translation initiation complex Source: Ensembl
  • IRES-dependent viral translational initiation Source: UniProtKB
  • positive regulation of mRNA binding Source: ParkinsonsUK-UCL
  • positive regulation of translation Source: ParkinsonsUK-UCL
  • translational initiation Source: UniProtKB
  • viral translational termination-reinitiation Source: UniProtKB
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionInitiation factor, RNA-binding
Biological processProtein biosynthesis

Enzyme and pathway databases

ReactomeiR-HSA-156827. L13a-mediated translational silencing of Ceruloplasmin expression.
R-HSA-72649. Translation initiation complex formation.
R-HSA-72689. Formation of a pool of free 40S subunits.
R-HSA-72695. Formation of the ternary complex, and subsequently, the 43S complex.
R-HSA-72702. Ribosomal scanning and start codon recognition.
R-HSA-72706. GTP hydrolysis and joining of the 60S ribosomal subunit.

Names & Taxonomyi

Protein namesi
Recommended name:
Eukaryotic translation initiation factor 3 subunit DUniRule annotation
Short name:
eIF3dUniRule annotation
Alternative name(s):
Eukaryotic translation initiation factor 3 subunit 7UniRule annotation
eIF-3-zetaUniRule annotation
eIF3 p66
Gene namesi
Name:EIF3DUniRule annotation
Synonyms:EIF3S7UniRule annotation
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 22

Organism-specific databases

EuPathDBiHostDB:ENSG00000100353.17.
HGNCiHGNC:3278. EIF3D.
MIMi603915. gene.
neXtProtiNX_O15371.

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

Pathology & Biotechi

Involvement in diseasei

Defects in EIF3D are associated with some cancers, such as prostate, breast and colon cancers. Disease susceptibility may be associated with variations affecting the gene represented in this entry. Down-regulation inhibits proliferation of cancers (PubMed:25370813, PubMed:25322666, PubMed:25682860, PubMed:26617750, PubMed:26008152, PubMed:26036682, PubMed:27035563).7 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi249D → Q: Reduced binding to JUN mRNA; when associated with 262-I-A-263. 1 Publication1
Mutagenesisi262 – 263VY → IA: Reduced binding to JUN mRNA; when associated with Q-249. 1 Publication2
Mutagenesisi317 – 321TYINH → EYENA: Reduced binding to JUN mRNA. 1 Publication5

Organism-specific databases

DisGeNETi8664.
OpenTargetsiENSG00000100353.
PharmGKBiPA162384740.

Polymorphism and mutation databases

BioMutaiEIF3D.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001235201 – 548Eukaryotic translation initiation factor 3 subunit DAdd BLAST548

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei53N6-acetyllysineBy similarity1
Modified residuei161PhosphoserineCombined sources1
Modified residuei528PhosphoserineCombined sources1
Modified residuei529PhosphoserineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiO15371.
MaxQBiO15371.
PaxDbiO15371.
PeptideAtlasiO15371.
PRIDEiO15371.

PTM databases

iPTMnetiO15371.
PhosphoSitePlusiO15371.
SwissPalmiO15371.

Expressioni

Gene expression databases

BgeeiENSG00000100353.
CleanExiHS_EIF3D.
ExpressionAtlasiO15371. baseline and differential.
GenevisibleiO15371. HS.

Organism-specific databases

HPAiHPA045882.
HPA063330.
HPA066216.

Interactioni

Subunit structurei

Component of the eukaryotic translation initiation factor 3 (eIF-3) complex, which is composed of 13 subunits: EIF3A, EIF3B, EIF3C, EIF3D, EIF3E, EIF3F, EIF3G, EIF3H, EIF3I, EIF3J, EIF3K, EIF3L and EIF3M. The eIF-3 complex appears to include 3 stable modules: module A is composed of EIF3A, EIF3B, EIF3G and EIF3I; module B is composed of EIF3F, EIF3H, and EIF3M; and module C is composed of EIF3C, EIF3D, EIF3E, EIF3K and EIF3L. EIF3C of module C binds EIF3B of module A and EIF3H of module B, thereby linking the three modules. EIF3J is a labile subunit that binds to the eIF-3 complex via EIF3B. The eIF-3 complex interacts with RPS6KB1 under conditions of nutrient depletion. Mitogenic stimulation leads to binding and activation of a complex composed of MTOR and RPTOR, leading to phosphorylation and release of RPS6KB1 and binding of EIF4B to eIF-3.UniRule annotation5 Publications
(Microbial infection) Interacts with Norwalk virus VPg protein (PubMed:12773399).1 Publication

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi114213. 87 interactors.
CORUMiO15371.
DIPiDIP-32870N.
IntActiO15371. 70 interactors.
MINTiO15371.
STRINGi9606.ENSP00000216190.

Structurei

3D structure databases

ProteinModelPortaliO15371.
SMRiO15371.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni285 – 299RNA gateBy similarityAdd BLAST15

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi530 – 547Asp/Glu-rich (highly acidic)Add BLAST18

Domaini

The RNA gate region regulates mRNA cap recognition to prevent promiscuous mRNA-binding before assembly of EIF3D into the full eukaryotic translation initiation factor 3 (eIF-3) complex.1 Publication

Sequence similaritiesi

Belongs to the eIF-3 subunit D family.UniRule annotation

Phylogenomic databases

eggNOGiKOG2479. Eukaryota.
ENOG410XP1E. LUCA.
GeneTreeiENSGT00390000002667.
HOGENOMiHOG000241593.
HOVERGENiHBG000849.
InParanoidiO15371.
KOiK03251.
OMAiDRIFHTV.
OrthoDBiEOG091G07IK.
PhylomeDBiO15371.
TreeFamiTF101519.

Family and domain databases

HAMAPiMF_03003. eIF3d. 1 hit.
InterProiView protein in InterPro
IPR007783. eIF3d.
PANTHERiPTHR12399. PTHR12399. 1 hit.
PfamiView protein in Pfam
PF05091. eIF-3_zeta. 1 hit.
PIRSFiPIRSF016281. EIF-3_zeta. 1 hit.

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O15371-1) [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
MAKFMTPVIQ DNPSGWGPCA VPEQFRDMPY QPFSKGDRLG KVADWTGATY 
        60         70         80         90        100
QDKRYTNKYS SQFGGGSQYA YFHEEDESSF QLVDTARTQK TAYQRNRMRF 
       110        120        130        140        150
AQRNLRRDKD RRNMLQFNLQ ILPKSAKQKE RERIRLQKKF QKQFGVRQKW 
       160        170        180        190        200
DQKSQKPRDS SVEVRSDWEV KEEMDFPQLM KMRYLEVSEP QDIECCGALE 
       210        220        230        240        250
YYDKAFDRIT TRSEKPLRSI KRIFHTVTTT DDPVIRKLAK TQGNVFATDA 
       260        270        280        290        300
ILATLMSCTR SVYSWDIVVQ RVGSKLFFDK RDNSDFDLLT VSETANEPPQ 
       310        320        330        340        350
DEGNSFNSPR NLAMEATYIN HNFSQQCLRM GKERYNFPNP NPFVEDDMDK 
       360        370        380        390        400
NEIASVAYRY RRWKLGDDID LIVRCEHDGV MTGANGEVSF INIKTLNEWD 
       410        420        430        440        450
SRHCNGVDWR QKLDSQRGAV IATELKNNSY KLARWTCCAL LAGSEYLKLG 
       460        470        480        490        500
YVSRYHVKDS SRHVILGTQQ FKPNEFASQI NLSVENAWGI LRCVIDICMK 
       510        520        530        540 
LEEGKYLILK DPNKQVIRVY SLPDGTFSSD EDEEEEEEEE EEEEEEET
Length:548
Mass (Da):63,973
Last modified:January 1, 1998 - v1
Checksum:i7FE0448EC3BE1711
GO
Isoform 2 (identifier: O15371-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     54-102: Missing.

Note: No experimental confirmation available.
Show »
Length:499
Mass (Da):58,140
Checksum:iE6E9019C723159C2
GO
Isoform 3 (identifier: O15371-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     137-151: Missing.

Note: No experimental confirmation available.
Show »
Length:533
Mass (Da):62,040
Checksum:i32AA0A0A31EEF2CD
GO

Mass spectrometryi

Molecular mass is 63972.9 Da from positions 1 - 548. 1 Publication
Molecular mass is 64046.7±1.4 Da from positions 1 - 548. Determined by MALDI. 1 Publication

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_074184310R → C1 PublicationCorresponds to variant dbSNP:rs745920273Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05547354 – 102Missing in isoform 2. 1 PublicationAdd BLAST49
Alternative sequenceiVSP_055474137 – 151Missing in isoform 3. 1 PublicationAdd BLAST15

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U54558 mRNA. Translation: AAD03466.1.
BT007381 mRNA. Translation: AAP36045.1.
CR456489 mRNA. Translation: CAG30375.1.
AK300199 mRNA. Translation: BAG61970.1.
AK301284 mRNA. Translation: BAG62843.1.
AK312939 mRNA. Translation: BAG35781.1.
AL022313 Genomic DNA. No translation available.
CH471095 Genomic DNA. Translation: EAW60109.1.
BC000328 mRNA. Translation: AAH00328.1.
BC000469 mRNA. Translation: AAH00469.1.
BC014912 mRNA. Translation: AAH14912.1.
BC080515 mRNA. Translation: AAH80515.1.
BC093100 mRNA. Translation: AAH93100.1.
BC093686 mRNA. Translation: AAH93686.1.
BC101477 mRNA. Translation: AAI01478.1.
CCDSiCCDS13930.1. [O15371-1]
RefSeqiNP_003744.1. NM_003753.3. [O15371-1]
UniGeneiHs.55682.

Genome annotation databases

EnsembliENST00000216190; ENSP00000216190; ENSG00000100353. [O15371-1]
ENST00000405442; ENSP00000385812; ENSG00000100353. [O15371-1]
GeneIDi8664.
KEGGihsa:8664.
UCSCiuc003apr.4. human. [O15371-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiEIF3D_HUMAN
AccessioniPrimary (citable) accession number: O15371
Secondary accession number(s): A8MWD3
, B2R7D4, B4DTF8, B4DVY1, Q3MJD9, Q5M9Q6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 1, 1998
Last modified: March 28, 2018
This is version 171 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