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P49770 (EI2BB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 121. 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·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Translation initiation factor eIF-2B subunit beta
Alternative name(s):
S20I15
S20III15
eIF-2B GDP-GTP exchange factor subunit beta
Gene names
Name:EIF2B2
Synonyms:EIF2BB
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length351 AA.
Sequence statusComplete.
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.7 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12

Sequence similarities

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

Sequence caution

The sequence AAC42002.1 differs from that shown. Reason: Frameshift at several positions.

Ontologies

Keywords
   Biological processProtein biosynthesis
   DiseaseDisease mutation
Leukodystrophy
   Molecular functionInitiation factor
   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

central nervous system development

Inferred from mutant phenotype Ref.9. Source: UniProtKB

gene expression

Traceable author statement. Source: Reactome

myelination

Inferred from mutant phenotype PubMed 14566705. 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 translational initiation

Traceable author statement PubMed 15060152. Source: UniProtKB

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_functionATP binding

Inferred from direct assay PubMed 11323413. Source: UniProtKB

GTP binding

Inferred from direct assay PubMed 11323413. Source: UniProtKB

translation initiation factor activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 351351Translation initiation factor eIF-2B subunit beta
PRO_0000156061

Natural variations

Natural variant851V → E in VWM. Ref.10
VAR_068451
Natural variant1711S → F in VWM; with ovarian failure. Ref.8 Ref.9
VAR_016842
Natural variant1961P → S in VWM. Ref.9
VAR_068452
Natural variant2001G → V in VWM. Ref.9
VAR_068453
Natural variant2131E → G in VWM; with and without ovarian failure. Ref.7 Ref.8 Ref.9 Ref.12
VAR_012289
Natural variant2681C → Y in VWM. Ref.11
VAR_068454
Natural variant2731K → R in VWM. Ref.7
VAR_012321
Natural variant3161V → D in VWM. Ref.7
VAR_012290
Natural variant3291G → V in VWM. Ref.7
VAR_012322

Experimental info

Sequence conflict61A → K in AAC42002. Ref.2
Sequence conflict231K → T in AAC42002. Ref.2
Sequence conflict301S → R in AAC42002. Ref.2
Sequence conflict351A → V in AAC42002. Ref.2
Sequence conflict521S → R in AAC42002. Ref.2
Sequence conflict95 – 1017RLHGRSD → DSMDAAT in AAC42002. Ref.2
Sequence conflict1101H → D in AAC42002. Ref.2

Sequences

Sequence LengthMass (Da)Tools
P49770 [UniParc].

Last modified May 30, 2000. Version 3.
Checksum: C29FE477143F545A

FASTA35138,990
        10         20         30         40         50         60 
MPGSAAKGSE LSERIESFVE TLKRGGGPRS SEEMARETLG LLRQIITDHR WSNAGELMEL 

        70         80         90        100        110        120 
IRREGRRMTA AQPSETTVGN MVRRVLKIIR EEYGRLHGRS DESDQQESLH KLLTSGGLNE 

       130        140        150        160        170        180 
DFSFHYAQLQ SNIIEAINEL LVELEGTMEN IAAQALEHIH SNEVIMTIGF SRTVEAFLKE 

       190        200        210        220        230        240 
AARKRKFHVI VAECAPFCQG HEMAVNLSKA GIETTVMTDA AIFAVMSRVN KVIIGTKTIL 

       250        260        270        280        290        300 
ANGALRAVTG THTLALAAKH HSTPLIVCAP MFKLSPQFPN EEDSFHKFVA PEEVLPFTEG 

       310        320        330        340        350 
DILEKVSVHC PVFDYVPPEL ITLFISNIGG NAPSYIYRLM SELYHPDDHV L 

« Hide

References

« Hide 'large scale' references
[1]Yu W., Sarginson J., Gibbs R.A.
Submitted (NOV-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[2]"Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease."
Sherrington R., Rogaev E.I., Liang Y., Rogaeva E.A., Levesque G., Ikeda M., Chi H., Lin C., Li G., Holman K., Tsuda T., Mar L., Foncin J.-F., Bruni A.C., Montesi M.P., Sorbi S., Rainero I., Pinessi L. expand/collapse author list , Nee L., Chumakov I., Pollen D., Brookes A., Sanseau P., Polinsky R.J., Wasco W., da Silva H.A.R., Haines J.L., Pericak-Vance M.A., Tanzi R.E., Roses A.D., Fraser P.E., Rommens J.M., St George-Hyslop P.H.
Nature 375:754-760(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Brain.
[3]"The DNA sequence and analysis of human chromosome 14."
Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. expand/collapse author list , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J.
Nature 421:601-607(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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].
Tissue: Lung.
[5]"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].
[6]"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"Subunits of the translation initiation factor eIF2B are mutant in leukoencephalopathy with vanishing white matter."
Leegwater P.A.J., Vermeulen G., Koenst A.A.M., Naidu S., Mulders J., Visser A., Kersbergen P., Mobach D., Fonds D., van Berkel C.G.M., Lemmers R.J.L.F., Frants R.R., Oudejans C.B.M., Schutgens R.B.H., Pronk J.C., van der Knaap M.S.
Nat. Genet. 29:383-388(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VWM GLY-213; ARG-273; ASP-316 AND VAL-329.
[8]"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 PHE-171 AND GLY-213.
[9]"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 PHE-171; SER-196; VAL-200 AND GLY-213.
[10]"Adult-onset leukoencephalopathies with vanishing white matter with novel missense mutations in EIF2B2, EIF2B3, and EIF2B5."
Matsukawa T., Wang X., Liu R., Wortham N.C., Onuki Y., Kubota A., Hida A., Kowa H., Fukuda Y., Ishiura H., Mitsui J., Takahashi Y., Aoki S., Takizawa S., Shimizu J., Goto J., Proud C.G., Tsuji S.
Neurogenetics 12:259-261(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VWM GLU-85.
[11]"Vanishing white matter disease caused by EIF2B2 mutation with the presentation of an adrenoleukodystrophy phenotype."
Alsalem A., Shaheen R., Alkuraya F.S.
Gene 496:141-143(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VWM TYR-268.
[12]"Vanishing white matter disease: an Italian case with A638G mutation in exon 5 of EIF2B2 gene, an unusual early onset and a long course."
Sambati L., Agati R., Bacci A., Bianchi S., Capellari S.
Neurol. Sci. 34:1235-1238(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT VWM GLY-213.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF035280 mRNA. Translation: AAB88176.1.
L40395 mRNA. Translation: AAC42002.1. Frameshift.
AC006530 Genomic DNA. Translation: AAD30183.1.
BC011750 mRNA. Translation: AAH11750.1.
RefSeqNP_055054.1. NM_014239.3.
UniGeneHs.409137.

3D structure databases

ProteinModelPortalP49770.
SMRP49770. Positions 11-347.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114409. 35 interactions.
IntActP49770. 6 interactions.
STRING9606.ENSP00000266126.

PTM databases

PhosphoSiteP49770.

Polymorphism databases

DMDM6226858.

Proteomic databases

PaxDbP49770.
PeptideAtlasP49770.
PRIDEP49770.

Protocols and materials databases

DNASU8892.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000266126; ENSP00000266126; ENSG00000119718.
GeneID8892.
KEGGhsa:8892.
UCSCuc001xrc.2. human.

Organism-specific databases

CTD8892.
GeneCardsGC14P075469.
HGNCHGNC:3258. EIF2B2.
HPAHPA005841.
HPA048028.
MIM603896. phenotype.
606454. gene.
neXtProtNX_P49770.
Orphanet99854. Cree leukoencephalopathy.
157716. Late infantile CACH syndrome.
99853. Ovarioleukodystrophy.
PharmGKBPA27689.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1184.
HOGENOMHOG000208487.
HOVERGENHBG051458.
InParanoidP49770.
KOK03754.
OMARIITDHR.
OrthoDBEOG7N0C4T.
PhylomeDBP49770.
TreeFamTF101506.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpressP49770.
BgeeP49770.
CleanExHS_EIF2B2.
GenevestigatorP49770.

Family and domain databases

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

Other

GeneWikiEIF2B2.
GenomeRNAi8892.
NextBio33395.
PROP49770.
SOURCESearch...

Entry information

Entry nameEI2BB_HUMAN
AccessionPrimary (citable) accession number: P49770
Secondary accession number(s): O43201
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 30, 2000
Last modified: April 16, 2014
This is version 121 of the entry and version 3 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 14

Human chromosome 14: entries, gene names and cross-references to MIM