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Q9UI10 (EI2BD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Translation initiation factor eIF-2B subunit delta
Alternative name(s):
eIF-2B GDP-GTP exchange factor subunit delta
Gene names
Name:EIF2B4
Synonyms:EIF2BD
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length523 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the exchange of eukaryotic initiation factor 2-bound GDP for GTP.

Subunit structure

Complex of five different subunits; alpha, beta, gamma, delta and epsilon.

Involvement in disease

Leukodystrophy with vanishing white matter (VWM) [MIM:603896]: A leukodystrophy that occurs mainly in children. Neurological signs include progressive cerebellar ataxia, spasticity, inconstant optic atrophy and relatively preserved mental abilities. The disease is chronic-progressive with, in most individuals, additional episodes of rapid deterioration following febrile infections or minor head trauma. While childhood onset is the most common form of the disorder, some severe forms are apparent at birth. A severe, early-onset form seen among the Cree and Chippewayan populations of Quebec and Manitoba is called Cree leukoencephalopathy. Milder forms may not become evident until adolescence or adulthood. Some females with milder forms of the disease who survive to adolescence exhibit ovarian dysfunction. This variant of the disorder is called ovarioleukodystrophy.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13 Ref.14 Ref.15

Sequence similarities

Belongs to the eIF-2B alpha/beta/delta subunits family.

Sequence caution

The sequence CAB57305.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
   Biological processProtein biosynthesis
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Leukodystrophy
   Molecular functionInitiation factor
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcellular protein metabolic process

Traceable author statement. Source: Reactome

cellular response to stimulus

Inferred from direct assay PubMed 8626696. Source: UniProtKB

gene expression

Traceable author statement. Source: Reactome

myelination

Inferred from mutant phenotype PubMed 14566705. Source: UniProtKB

negative regulation of translational initiation

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of translational initiation in response to stress

Inferred from sequence or structural similarity. Source: UniProtKB

oligodendrocyte development

Inferred from mutant phenotype PubMed 15217090. Source: UniProtKB

ovarian follicle development

Inferred from mutant phenotype PubMed 15507143. Source: UniProtKB

regulation of GTPase activity

Inferred from direct assay PubMed 11323413. Source: GOC

regulation of translation

Non-traceable author statement PubMed 12556349. Source: UniProtKB

regulation of translational initiation

Inferred from Biological aspect of Ancestor. Source: RefGenome

response to glucose

Inferred from sequence or structural similarity. Source: UniProtKB

response to heat

Inferred from sequence or structural similarity. Source: UniProtKB

response to peptide hormone

Inferred from sequence or structural similarity. Source: UniProtKB

translation

Traceable author statement. Source: Reactome

translational initiation

Inferred from direct assay PubMed 16289705. Source: UniProtKB

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 11323413. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

eukaryotic translation initiation factor 2B complex

Inferred from direct assay PubMed 11323413PubMed 15060152. Source: UniProtKB

   Molecular_functiontranslation initiation factor activity

Inferred from electronic annotation. Source: UniProtKB-KW

translation initiation factor binding

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: 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.
Isoform 2 (identifier: Q9UI10-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-10: MAAVAVAVRE → MPTQQPAAPSTRAPKPSRSLSGSLCALFSDA
     71-71: Missing.
Isoform 3 (identifier: Q9UI10-3)

The sequence of this isoform differs from the canonical sequence as follows:
     71-71: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.12
Chain2 – 523522Translation initiation factor eIF-2B subunit delta
PRO_0000156067

Amino acid modifications

Modified residue21N-acetylalanine Ref.12
Modified residue861Phosphothreonine Ref.7 Ref.9 Ref.10

Natural variations

Alternative sequence1 – 1010MAAVAVAVRE → MPTQQPAAPSTRAPKPSRSL SGSLCALFSDA in isoform 2.
VSP_001433
Alternative sequence711Missing in isoform 2 and isoform 3.
VSP_040130
Natural variant931A → V.
Corresponds to variant rs34155621 [ dbSNP | Ensembl ].
VAR_048918
Natural variant2091R → Q in VWM. Ref.15
VAR_068455
Natural variant2281A → V in VWM. Ref.13
VAR_015405
Natural variant2691L → R in VWM. Ref.15
VAR_068456
Natural variant3061R → G. Ref.13
Corresponds to variant rs78599355 [ dbSNP | Ensembl ].
VAR_015406
Natural variant3571R → Q in VWM. Ref.13
VAR_015407
Natural variant3741R → C in VWM. Ref.13 Ref.15
VAR_015408
Natural variant4651C → R in VWM; with ovarian failure. Ref.14
VAR_016843
Natural variant4891Y → H in VWM; with ovarian failure. Ref.14
VAR_016844

Experimental info

Sequence conflict1971S → T in CAB57260. Ref.2
Sequence conflict1971S → T in CAB57261. Ref.2
Sequence conflict1971S → T in CAB57304. Ref.2
Sequence conflict1971S → T in CAB57305. Ref.2
Sequence conflict3231A → S in AAF17195. Ref.1
Sequence conflict4811S → L in AAF17195. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 12, 2003. Version 2.
Checksum: 5F38CF10CAD5A45E

FASTA52357,557
        10         20         30         40         50         60 
MAAVAVAVRE DSGSGMKAEL PPGPGAVGRE MTKEEKLQLR KEKKQQKKKR KEEKGAEPET 

        70         80         90        100        110        120 
GSAVSAAQCQ VGPTRELPES GIQLGTPREK VPAGRSKAEL RAERRAKQEA ERALKQARKG 

       130        140        150        160        170        180 
EQGGPPPKAS PSTAGETPSG VKRLPEYPQV DDLLLRRLVK KPERQQVPTR KDYGSKVSLF 

       190        200        210        220        230        240 
SHLPQYSRQN SLTQFMSIPS SVIHPAMVRL GLQYSQGLVS GSNARCIALL RALQQVIQDY 

       250        260        270        280        290        300 
TTPPNEELSR DLVNKLKPYM SFLTQCRPLS ASMHNAIKFL NKEITSVGSS KREEEAKSEL 

       310        320        330        340        350        360 
RAAIDRYVQE KIVLAAQAIS RFAYQKISNG DVILVYGCSS LVSRILQEAW TEGRRFRVVV 

       370        380        390        400        410        420 
VDSRPWLEGR HTLRSLVHAG VPASYLLIPA ASYVLPEVSK VLLGAHALLA NGSVMSRVGT 

       430        440        450        460        470        480 
AQLALVARAH NVPVLVCCET YKFCERVQTD AFVSNELDDP DDLQCKRGEH VALANWQNHA 

       490        500        510        520 
SLRLLNLVYD VTPPELVDLV ITELGMIPCS SVPVVLRVKS SDQ 

« Hide

Isoform 2 [UniParc].

Checksum: C65253AD9431E074
Show »

FASTA54359,615
Isoform 3 [UniParc].

Checksum: D9A7E6FD35CD75F1
Show »

FASTA52257,458

References

« Hide 'large scale' references
[1]"Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning."
Hu R.-M., Han Z.-G., Song H.-D., Peng Y.-D., Huang Q.-H., Ren S.-X., Gu Y.-J., Huang C.-H., Li Y.-B., Jiang C.-L., Fu G., Zhang Q.-H., Gu B.-W., Dai M., Mao Y.-F., Gao G.-F., Rong R., Ye M. expand/collapse author list , Zhou J., Xu S.-H., Gu J., Shi J.-X., Jin W.-R., Zhang C.-K., Wu T.-M., Huang G.-Y., Chen Z., Chen M.-D., Chen J.-L.
Proc. Natl. Acad. Sci. U.S.A. 97:9543-9548(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Adrenal gland.
[2]"cDNA cloning, genomic organization and chromosomal localization of the human eIF2B delta subunit."
Wightman P.J., Bonthron D.T.
Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORMS 1; 2 AND 3).
[3]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Lung and Testis.
[6]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[7]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-86, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[8]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-86, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[10]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-86, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[13]"Mutations in each of the five subunits of translation initiation factor eIF2B can cause leukoencephalopathy with vanishing white matter."
van der Knaap M.S., Leegwater P.A.J., Koenst A.A.M., Visser A., Naidu S., Oudejans C.B.M., Schutgens R.B.H., Pronk J.C.
Ann. Neurol. 51:264-270(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VWM VAL-228; GLN-357 AND CYS-374, VARIANT GLY-306.
[14]"Ovarian failure related to eukaryotic initiation factor 2B mutations."
Fogli A., Rodriguez D., Eymard-Pierre E., Bouhour F., Labauge P., Meaney B.F., Zeesman S., Kaneski C.R., Schiffmann R., Boespflug-Tanguy O.
Am. J. Hum. Genet. 72:1544-1550(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VWM ARG-465 AND HIS-489.
[15]"Identification of ten novel mutations in patients with eIF2B-related disorders."
Ohlenbusch A., Henneke M., Brockmann K., Goerg M., Hanefeld F., Kohlschutter A., Gartner J.
Hum. Mutat. 25:411-411(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VWM GLN-209; ARG-269 AND CYS-374.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF112207 mRNA. Translation: AAF17195.1.
AJ011305 mRNA. Translation: CAB57260.1.
AJ011306 mRNA. Translation: CAB57261.1.
AJ011307, AJ011308 Genomic DNA. Translation: CAB57304.1.
AJ011307, AJ011308 Genomic DNA. Translation: CAB57305.1. Sequence problems.
AC074117 Genomic DNA. Translation: AAY14843.1.
CH471053 Genomic DNA. Translation: EAX00591.1.
BC001870 mRNA. Translation: AAH01870.1.
BC091502 mRNA. Translation: AAH91502.1.
RefSeqNP_001029288.1. NM_001034116.1.
NP_056451.3. NM_015636.3.
NP_751945.2. NM_172195.3.
UniGeneHs.169474.

3D structure databases

ProteinModelPortalQ9UI10.
SMRQ9UI10. Positions 219-517.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114407. 6 interactions.
IntActQ9UI10. 7 interactions.
MINTMINT-4990902.
STRING9606.ENSP00000394869.

PTM databases

PhosphoSiteQ9UI10.

Polymorphism databases

DMDM28381357.

Proteomic databases

PaxDbQ9UI10.
PRIDEQ9UI10.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000347454; ENSP00000233552; ENSG00000115211. [Q9UI10-1]
ENST00000445933; ENSP00000394397; ENSG00000115211. [Q9UI10-3]
ENST00000451130; ENSP00000394869; ENSG00000115211. [Q9UI10-2]
GeneID8890.
KEGGhsa:8890.
UCSCuc002rjz.3. human. [Q9UI10-2]
uc002rka.3. human. [Q9UI10-1]
uc002rkc.3. human. [Q9UI10-3]

Organism-specific databases

CTD8890.
GeneCardsGC02M027587.
HGNCHGNC:3260. EIF2B4.
HPACAB032234.
HPA039993.
MIM603896. phenotype.
606687. gene.
neXtProtNX_Q9UI10.
Orphanet99854. Cree leukoencephalopathy.
157716. Late infantile CACH syndrome.
99853. Ovarioleukodystrophy.
PharmGKBPA27691.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1184.
HOGENOMHOG000176924.
HOVERGENHBG051459.
InParanoidQ9UI10.
KOK03680.
OrthoDBEOG7XSTF0.
PhylomeDBQ9UI10.
TreeFamTF101508.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpressQ9UI10.
BgeeQ9UI10.
CleanExHS_EIF2B4.
GenevestigatorQ9UI10.

Family and domain databases

InterProIPR000649. IF-2B-related.
[Graphical view]
PfamPF01008. IF-2B. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiEIF2B4.
GenomeRNAi8890.
NextBio33383.
PROQ9UI10.
SOURCESearch...

Entry information

Entry nameEI2BD_HUMAN
AccessionPrimary (citable) accession number: Q9UI10
Secondary accession number(s): Q53RY7 expand/collapse secondary AC list , Q5BJF4, Q9BUV9, Q9UBG4, Q9UIQ9, Q9UJ95
Entry history
Integrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: February 12, 2003
Last modified: April 16, 2014
This is version 122 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 2

Human chromosome 2: entries, gene names and cross-references to MIM