Q9UI10 · EI2BD_HUMAN
- ProteinTranslation initiation factor eIF2B subunit delta
- GeneEIF2B4
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids523 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Acts as a component of the translation initiation factor 2B (eIF2B) complex, which catalyzes the exchange of GDP for GTP on eukaryotic initiation factor 2 (eIF2) gamma subunit (PubMed:25858979, PubMed:27023709, PubMed:31048492).
Its guanine nucleotide exchange factor activity is repressed when bound to eIF2 complex phosphorylated on the alpha subunit, thereby limiting the amount of methionyl-initiator methionine tRNA available to the ribosome and consequently global translation is repressed (PubMed:25858979, PubMed:31048492).
Its guanine nucleotide exchange factor activity is repressed when bound to eIF2 complex phosphorylated on the alpha subunit, thereby limiting the amount of methionyl-initiator methionine tRNA available to the ribosome and consequently global translation is repressed (PubMed:25858979, PubMed:31048492).
Activity regulation
Activated by the chemical integrated stress response (ISR) inhibitor ISRIB which stimulates guanine nucleotide exchange factor activity for both phosphorylated and unphosphorylated eIF2.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | cytosol | |
Cellular Component | eukaryotic translation initiation factor 2B complex | |
Molecular Function | guanyl-nucleotide exchange factor activity | |
Molecular Function | translation initiation factor activity | |
Molecular Function | translation initiation factor binding | |
Biological Process | cytoplasmic translational initiation | |
Biological Process | myelination | |
Biological Process | oligodendrocyte development | |
Biological Process | ovarian follicle development | |
Biological Process | regulation of translation | |
Biological Process | response to glucose | |
Biological Process | response to heat | |
Biological Process | response to peptide hormone | |
Biological Process | T cell receptor signaling pathway | |
Biological Process | translational initiation |
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTranslation initiation factor eIF2B subunit delta
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9UI10
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Leukoencephalopathy with vanishing white matter 4 (VWM4)
- Note
- DescriptionAn autosomal recessive brain disease characterized by neurological features including progressive cerebellar ataxia, spasticity, and cognitive deficits. Brain imaging shows abnormal white matter that vanishes over time and is replaced by cerebrospinal fluid. Disease severity ranges from fatal infantile forms to adult forms without neurological deterioration. The disease is progressive with, in most individuals, additional episodes of rapid deterioration following febrile infections or minor head trauma. Death may occurs after a variable period after disease onset, usually following an episode of fever and coma. A subset of affected females with milder forms of the disease who survive to adolescence exhibit ovarian dysfunction. This variant of the disorder is called ovarioleukodystrophy.
- See alsoMIM:620314
Natural variants in VWM4
Variant ID | Position(s) | Change | Description | |
---|---|---|---|---|
VAR_068455 | 209 | R>Q | in VWM4; dbSNP:rs113994028 | |
VAR_015405 | 228 | A>V | in VWM4; dbSNP:rs113994027 | |
VAR_068456 | 269 | L>R | in VWM4; dbSNP:rs113994031 | |
VAR_015407 | 357 | R>Q | in VWM4; dbSNP:rs113994033 | |
VAR_015408 | 374 | R>C | in VWM4; dbSNP:rs113994035 | |
VAR_016843 | 465 | C>R | in VWM4; with ovarian failure; dbSNP:rs113994038 | |
VAR_016844 | 489 | Y>H | in VWM4; with ovarian failure; dbSNP:rs113994040 |
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_048918 | 93 | in dbSNP:rs34155621 | |||
Sequence: A → V | ||||||
Natural variant | VAR_068455 | 209 | in VWM4; dbSNP:rs113994028 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_015405 | 228 | in VWM4; dbSNP:rs113994027 | |||
Sequence: A → V | ||||||
Natural variant | VAR_068456 | 269 | in VWM4; dbSNP:rs113994031 | |||
Sequence: L → R | ||||||
Natural variant | VAR_015406 | 306 | in dbSNP:rs78599355 | |||
Sequence: R → G | ||||||
Natural variant | VAR_015407 | 357 | in VWM4; dbSNP:rs113994033 | |||
Sequence: R → Q | ||||||
Natural variant | VAR_015408 | 374 | in VWM4; dbSNP:rs113994035 | |||
Sequence: R → C | ||||||
Natural variant | VAR_016843 | 465 | in VWM4; with ovarian failure; dbSNP:rs113994038 | |||
Sequence: C → R | ||||||
Natural variant | VAR_016844 | 489 | in VWM4; with ovarian failure; dbSNP:rs113994040 | |||
Sequence: Y → H |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 624 variants from UniProt as well as other sources including ClinVar and dbSNP.
Keywords
- Disease
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylalanine | ||||
Sequence: A | |||||||
Chain | PRO_0000156067 | 2-523 | UniProt | Translation initiation factor eIF2B subunit delta | |||
Sequence: AAVAVAVREDSGSGMKAELPPGPGAVGREMTKEEKLQLRKEKKQQKKKRKEEKGAEPETGSAVSAAQCQVGPTRELPESGIQLGTPREKVPAGRSKAELRAERRAKQEAERALKQARKGEQGGPPPKASPSTAGETPSGVKRLPEYPQVDDLLLRRLVKKPERQQVPTRKDYGSKVSLFSHLPQYSRQNSLTQFMSIPSSVIHPAMVRLGLQYSQGLVSGSNARCIALLRALQQVIQDYTTPPNEELSRDLVNKLKPYMSFLTQCRPLSASMHNAIKFLNKEITSVGSSKREEEAKSELRAAIDRYVQEKIVLAAQAISRFAYQKISNGDVILVYGCSSLVSRILQEAWTEGRRFRVVVVDSRPWLEGRHTLRSLVHAGVPASYLLIPAASYVLPEVSKVLLGAHALLANGSVMSRVGTAQLALVARAHNVPVLVCCETYKFCERVQTDAFVSNELDDPDDLQCKRGEHVALANWQNHASLRLLNLVYDVTPPELVDLVITELGMIPCSSVPVVLRVKSSDQ | |||||||
Modified residue | 12 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 12 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 86 | UniProt | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 86 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 130 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 130 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 133 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 137 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 139 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 191 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Interaction
Subunit
Component of the translation initiation factor 2B (eIF2B) complex which is a heterodecamer of two sets of five different subunits: alpha, beta, gamma, delta and epsilon. Subunits alpha, beta and delta comprise a regulatory subcomplex and subunits epsilon and gamma comprise a catalytic subcomplex (PubMed:25858979, PubMed:27023709, PubMed:31048492).
Within the complex, the hexameric regulatory complex resides at the center, with the two heterodimeric catalytic subcomplexes bound on opposite sides (PubMed:31048492).
Within the complex, the hexameric regulatory complex resides at the center, with the two heterodimeric catalytic subcomplexes bound on opposite sides (PubMed:31048492).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9UI10 | AGT P01019 | 3 | EBI-2340132, EBI-751728 | |
BINARY | Q9UI10 | EIF2B2 P49770 | 9 | EBI-2340132, EBI-718773 | |
BINARY | Q9UI10 | EIF2B2 Q53XC2 | 4 | EBI-2340132, EBI-10288660 | |
BINARY | Q9UI10 | FOS P01100 | 3 | EBI-2340132, EBI-852851 | |
BINARY | Q9UI10 | GATM P50440 | 3 | EBI-2340132, EBI-2552594 | |
BINARY | Q9UI10 | GRB2 P62993 | 3 | EBI-2340132, EBI-401755 | |
BINARY | Q9UI10 | KLKB1 P03952 | 3 | EBI-2340132, EBI-10087153 | |
BINARY | Q9UI10 | LPL P06858 | 3 | EBI-2340132, EBI-715909 | |
XENO | Q9UI10 | M P06821 | 3 | EBI-2340132, EBI-2547404 | |
XENO | Q9UI10 | M Q6DPW5 | 2 | EBI-2340132, EBI-12562156 | |
XENO | Q9UI10 | M2 C5E519 | 2 | EBI-2340132, EBI-12562139 | |
XENO | Q9UI10 | M2 Q20MH8 | 3 | EBI-2340132, EBI-12576433 | |
BINARY | Q9UI10 | UQCRC1 P31930 | 3 | EBI-2340132, EBI-1052596 | |
BINARY | Q9UI10 | VHL P40337-2 | 3 | EBI-2340132, EBI-12157263 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-147 | Disordered | ||||
Sequence: MAAVAVAVREDSGSGMKAELPPGPGAVGREMTKEEKLQLRKEKKQQKKKRKEEKGAEPETGSAVSAAQCQVGPTRELPESGIQLGTPREKVPAGRSKAELRAERRAKQEAERALKQARKGEQGGPPPKASPSTAGETPSGVKRLPEY | ||||||
Compositional bias | 92-118 | Basic and acidic residues | ||||
Sequence: PAGRSKAELRAERRAKQEAERALKQAR | ||||||
Region | 170-179 | May bind the chemical integrated stress response (ISR) inhibitor ISRIB | ||||
Sequence: RKDYGSKVSL |
Sequence similarities
Belongs to the eIF-2B alpha/beta/delta subunits family.
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 3 isoforms produced by Alternative splicing.
Q9UI10-1
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.
- Name1
- Length523
- Mass (Da)57,557
- Last updated2003-02-12 v2
- Checksum5F38CF10CAD5A45E
Q9UI10-2
- Name2
Q9UI10-3
- Name3
- Differences from canonical
- 71-71: Missing
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Sequence caution
Features
Showing features for alternative sequence, compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_001433 | 1-10 | in isoform 2 | |||
Sequence: MAAVAVAVRE → MPTQQPAAPSTRAPKPSRSLSGSLCALFSDA | ||||||
Alternative sequence | VSP_040130 | 71 | in isoform 2 and isoform 3 | |||
Sequence: Missing | ||||||
Compositional bias | 92-118 | Basic and acidic residues | ||||
Sequence: PAGRSKAELRAERRAKQEAERALKQAR | ||||||
Sequence conflict | 197 | in Ref. 2; CAB57260/CAB57261/CAB57304/CAB57305 | ||||
Sequence: S → T | ||||||
Sequence conflict | 323 | in Ref. 1; AAF17195 | ||||
Sequence: A → S | ||||||
Sequence conflict | 481 | in Ref. 1; AAF17195 | ||||
Sequence: S → L |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF112207 EMBL· GenBank· DDBJ | AAF17195.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ011305 EMBL· GenBank· DDBJ | CAB57260.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ011306 EMBL· GenBank· DDBJ | CAB57261.1 EMBL· GenBank· DDBJ | mRNA | ||
AJ011307 EMBL· GenBank· DDBJ | CAB57304.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ011308 EMBL· GenBank· DDBJ | CAB57304.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AJ011307 EMBL· GenBank· DDBJ | CAB57305.1 EMBL· GenBank· DDBJ | Genomic DNA | Sequence problems. | |
AJ011308 EMBL· GenBank· DDBJ | CAB57305.1 EMBL· GenBank· DDBJ | Genomic DNA | Sequence problems. | |
AC074117 EMBL· GenBank· DDBJ | AAY14843.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471053 EMBL· GenBank· DDBJ | EAX00591.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC001870 EMBL· GenBank· DDBJ | AAH01870.1 EMBL· GenBank· DDBJ | mRNA | ||
BC091502 EMBL· GenBank· DDBJ | AAH91502.1 EMBL· GenBank· DDBJ | mRNA |