P49770 (EI2BB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	351 AA.
Sequence status	Complete.
Protein existence	Evidence 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.6 Ref.7 Ref.8 Ref.9 Ref.10 Ref.11
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 process	Protein biosynthesis
Disease	Disease mutation Leukodystrophy
Molecular function	Initiation factor
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to stimulus Inferred from direct assay PubMed 8626696. Source: UniProtKB 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 translational initiation Traceable author statement PubMed 15060152. Source: UniProtKB response to glucose stimulus Inferred from sequence or structural similarity. Source: UniProtKB response to heat Inferred from sequence or structural similarity. Source: UniProtKB response to peptide hormone stimulus Inferred from sequence or structural similarity. Source: UniProtKB translational initiation Inferred from direct assay PubMed 16289705. Source: UniProtKB
Cellular_component	cytosol Traceable author statement. Source: Reactome eukaryotic translation initiation factor 2B complex Inferred from direct assay PubMed 11323413PubMed 15060152. Source: UniProtKB
Molecular_function	ATP 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 351	351	Translation initiation factor eIF-2B subunit beta		PRO_0000156061
Natural variations
	Natural variant	85	1	V → E in VWM. Ref.9		VAR_068451
	Natural variant	171	1	S → F in VWM; with ovarian failure. Ref.7 Ref.8		VAR_016842
	Natural variant	196	1	P → S in VWM. Ref.8		VAR_068452
	Natural variant	200	1	G → V in VWM. Ref.8		VAR_068453
	Natural variant	213	1	E → G in VWM; with and without ovarian failure. Ref.6 Ref.7 Ref.8 Ref.11		VAR_012289
	Natural variant	268	1	C → Y in VWM. Ref.10		VAR_068454
	Natural variant	273	1	K → R in VWM. Ref.6		VAR_012321
	Natural variant	316	1	V → D in VWM. Ref.6		VAR_012290
	Natural variant	329	1	G → V in VWM. Ref.6		VAR_012322
Experimental info
	Sequence conflict	6	1	A → K in AAC42002. Ref.2
	Sequence conflict	23	1	K → T in AAC42002. Ref.2
	Sequence conflict	30	1	S → R in AAC42002. Ref.2
	Sequence conflict	35	1	A → V in AAC42002. Ref.2
	Sequence conflict	52	1	S → R in AAC42002. Ref.2
	Sequence conflict	95 – 101	7	RLHGRSD → DSMDAAT in AAC42002. Ref.2
	Sequence conflict	110	1	H → D in AAC42002. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P49770 [UniParc]. Last modified May 30, 2000. Version 3. Checksum: C29FE477143F545A	FASTA	351	38,990
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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]	"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.
[7]	"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.
[8]	"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.
[9]	"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.
[10]	"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.
[11]	"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. 0:0-0(2012) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT VWM GLY-213.
+	Additional computationally mapped references.

Web resources

GeneReviews

Mendelian genes eukaryotic translation initiation factor 2B, subunit 2 beta, 39kDa (EIF2B2)

Leiden Open Variation Database (LOVD)

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.
IPI	IPI00028083.
RefSeq	NP_055054.1. NM_014239.3.
UniGene	Hs.409137.
3D structure databases
ProteinModelPortal	P49770.
ModBase	Search...
Protein-protein interaction databases
IntAct	P49770. 4 interactions.
STRING	9606.ENSP00000266126.
PTM databases
PhosphoSite	P49770.
Polymorphism databases
DMDM	6226858.
Proteomic databases
PaxDb	P49770.
PeptideAtlas	P49770.
PRIDE	P49770.
Protocols and materials databases
DNASU	8892.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000266126; ENSP00000266126; ENSG00000119718.
GeneID	8892.
KEGG	hsa:8892.
UCSC	uc001xrc.2. human.
Organism-specific databases
CTD	8892.
GeneCards	GC14P075469.
HGNC	HGNC:3258. EIF2B2.
HPA	HPA005841.
MIM	603896. phenotype. 606454. gene.
neXtProt	NX_P49770.
Orphanet	99854. Cree leukoencephalopathy. 157716. Late infantile CACH syndrome. 99853. Ovarioleukodystrophy.
PharmGKB	PA27689.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1184.
HOGENOM	HOG000208487.
HOVERGEN	HBG051458.
InParanoid	P49770.
KO	K03754.
OMA	FVSPHEV.
OrthoDB	EOG4JT05R.
PhylomeDB	P49770.
Enzyme and pathway databases
Reactome	REACT_17015. Metabolism of proteins. REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	P49770.
Bgee	P49770.
CleanEx	HS_EIF2B2.
Genevestigator	P49770.
GermOnline	ENSG00000119718. Homo sapiens.
Family and domain databases
InterPro	IPR000649. IF-2B-related. [Graphical view]
PANTHER	PTHR10233. PTHR10233. 1 hit.
Pfam	PF01008. IF-2B. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	8892.
NextBio	33395.
SOURCE	Search...

Entry information

Entry name

EI2BB_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 113 of the entry and version 3 of the sequence. [Complete history]

Entry status

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.