UniProtKB - O15371 (EIF3D_HUMAN)
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Protein
Eukaryotic translation initiation factor 3 subunit D
Gene
EIF3D
Organism
Homo sapiens (Human)
Status
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
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
Keywordsi
Molecular function | Initiation factor, RNA-binding |
Biological process | Protein biosynthesis |
Enzyme and pathway databases
Reactomei | R-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 annotationShort name: eIF3dUniRule annotation Alternative name(s): Eukaryotic translation initiation factor 3 subunit 7UniRule annotation eIF-3-zetaUniRule annotation eIF3 p66 |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000100353.17. |
HGNCi | HGNC:3278. EIF3D. |
MIMi | 603915. gene. |
neXtProti | NX_O15371. |
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 key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 249 | D → Q: Reduced binding to JUN mRNA; when associated with 262-I-A-263. 1 Publication | 1 | |
Mutagenesisi | 262 – 263 | VY → IA: Reduced binding to JUN mRNA; when associated with Q-249. 1 Publication | 2 | |
Mutagenesisi | 317 – 321 | TYINH → EYENA: Reduced binding to JUN mRNA. 1 Publication | 5 |
Organism-specific databases
DisGeNETi | 8664. |
OpenTargetsi | ENSG00000100353. |
PharmGKBi | PA162384740. |
Polymorphism and mutation databases
BioMutai | EIF3D. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000123520 | 1 – 548 | Eukaryotic translation initiation factor 3 subunit DAdd BLAST | 548 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 53 | N6-acetyllysineBy similarity | 1 | |
Modified residuei | 161 | PhosphoserineCombined sources | 1 | |
Modified residuei | 528 | PhosphoserineCombined sources | 1 | |
Modified residuei | 529 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
EPDi | O15371. |
MaxQBi | O15371. |
PaxDbi | O15371. |
PeptideAtlasi | O15371. |
PRIDEi | O15371. |
PTM databases
iPTMneti | O15371. |
PhosphoSitePlusi | O15371. |
SwissPalmi | O15371. |
Expressioni
Gene expression databases
Bgeei | ENSG00000100353. |
CleanExi | HS_EIF3D. |
ExpressionAtlasi | O15371. baseline and differential. |
Genevisiblei | O15371. HS. |
Organism-specific databases
HPAi | HPA045882. 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
Protein-protein interaction databases
BioGridi | 114213. 87 interactors. |
CORUMi | O15371. |
DIPi | DIP-32870N. |
IntActi | O15371. 70 interactors. |
MINTi | O15371. |
STRINGi | 9606.ENSP00000216190. |
Structurei
3D structure databases
ProteinModelPortali | O15371. |
SMRi | O15371. |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 285 – 299 | RNA gateBy similarityAdd BLAST | 15 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 530 – 547 | Asp/Glu-rich (highly acidic)Add BLAST | 18 |
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
eggNOGi | KOG2479. Eukaryota. ENOG410XP1E. LUCA. |
GeneTreei | ENSGT00390000002667. |
HOGENOMi | HOG000241593. |
HOVERGENi | HBG000849. |
InParanoidi | O15371. |
KOi | K03251. |
OMAi | DRIFHTV. |
OrthoDBi | EOG091G07IK. |
PhylomeDBi | O15371. |
TreeFami | TF101519. |
Family and domain databases
HAMAPi | MF_03003. eIF3d. 1 hit. |
InterProi | View protein in InterPro IPR007783. eIF3d. |
PANTHERi | PTHR12399. PTHR12399. 1 hit. |
Pfami | View protein in Pfam PF05091. eIF-3_zeta. 1 hit. |
PIRSFi | PIRSF016281. EIF-3_zeta. 1 hit. |
s (3)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative 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.
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
Mass spectrometryi
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_074184 | 310 | R → C1 PublicationCorresponds to variant dbSNP:rs745920273Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_055473 | 54 – 102 | Missing in isoform 2. 1 PublicationAdd BLAST | 49 | |
Alternative sequenceiVSP_055474 | 137 – 151 | Missing in isoform 3. 1 PublicationAdd BLAST | 15 |
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. |
CCDSi | CCDS13930.1. [O15371-1] |
RefSeqi | NP_003744.1. NM_003753.3. [O15371-1] |
UniGenei | Hs.55682. |
Genome annotation databases
Ensembli | ENST00000216190; ENSP00000216190; ENSG00000100353. [O15371-1] ENST00000405442; ENSP00000385812; ENSG00000100353. [O15371-1] |
GeneIDi | 8664. |
KEGGi | hsa:8664. |
UCSCi | uc003apr.4. human. [O15371-1] |
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Entry informationi
Entry namei | EIF3D_HUMAN | |
Accessioni | O15371Primary (citable) accession number: O15371 Secondary accession number(s): A8MWD3 Q5M9Q6 | |
Entry historyi | Integrated 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 statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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. |