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Q9NR50 (EI2BG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 118. 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 gamma
Alternative name(s):
eIF-2B GDP-GTP exchange factor subunit gamma
Gene names
Name:EIF2B3
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length452 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.11 Ref.12 Ref.13

Sequence similarities

Belongs to the eIF-2B gamma/epsilon subunits family.

Ontologies

Keywords
   Biological processProtein biosynthesis
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Leukodystrophy
   Molecular functionInitiation factor
   PTMAcetylation
   Technical termComplete proteome
Direct protein sequencing
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

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

regulation of GTPase activity

Inferred from direct assay PubMed 11323413. Source: GOC

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 Ref.1PubMed 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_functionguanyl-nucleotide exchange factor activity

Inferred from electronic annotation. Source: Ensembl

nucleotidyltransferase activity

Inferred from electronic annotation. Source: InterPro

translation initiation factor activity

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Note: Experimental confirmation may be lacking for some isoforms.
Isoform 1 (identifier: Q9NR50-1)

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: Q9NR50-2)

The sequence of this isoform differs from the canonical sequence as follows:
     402-452: SNIQGSVICNNAVIEKGADIKDCLIGSGQRIEAKAKRVNEVIVGNDQLMEI → YVSPCTHLRQR
Isoform 3 (identifier: Q9NR50-3)

The sequence of this isoform differs from the canonical sequence as follows:
     402-452: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 452452Translation initiation factor eIF-2B subunit gamma
PRO_0000156079

Amino acid modifications

Modified residue11N-acetylmethionine Ref.7 Ref.9 Ref.10

Natural variations

Alternative sequence402 – 45251SNIQG…QLMEI → YVSPCTHLRQR in isoform 2.
VSP_001436
Alternative sequence402 – 45251Missing in isoform 3.
VSP_001435
Natural variant271L → Q in VWM. Ref.13
VAR_068470
Natural variant471G → E in VWM. Ref.12
VAR_068471
Natural variant871A → V in VWM. Ref.11
VAR_015409
Natural variant2251R → Q in VWM. Ref.11 Ref.12
VAR_015410
Natural variant2881D → E.
Corresponds to variant rs3738247 [ dbSNP | Ensembl ].
VAR_048920
Natural variant3461I → T in VWM. Ref.12
VAR_068472

Experimental info

Sequence conflict3561S → G in BAB14770. Ref.2

Sequences

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

Last modified October 1, 2000. Version 1.
Checksum: 6F73137F59E52773

FASTA45250,240
        10         20         30         40         50         60 
MEFQAVVMAV GGGSRMTDLT SSIPKPLLPV GNKPLIWYPL NLLERVGFEE VIVVTTRDVQ 

        70         80         90        100        110        120 
KALCAEFKMK MKPDIVCIPD DADMGTADSL RYIYPKLKTD VLVLSCDLIT DVALHEVVDL 

       130        140        150        160        170        180 
FRAYDASLAM LMRKGQDSIE PVPGQKGKKK AVEQRDFIGV DSTGKRLLFM ANEADLDEEL 

       190        200        210        220        230        240 
VIKGSILQKH PRIRFHTGLV DAHLYCLKKY IVDFLMENGS ITSIRSELIP YLVRKQFSSA 

       250        260        270        280        290        300 
SSQQGQEEKE EDLKKKELKS LDIYSFIKEA NTLNLAPYDA CWNACRGDRW EDLSRSQVRC 

       310        320        330        340        350        360 
YVHIMKEGLC SRVSTLGLYM EANRQVPKLL SALCPEEPPV HSSAQIVSKH LVGVDSLIGP 

       370        380        390        400        410        420 
ETQIGEKSSI KRSVIGSSCL IKDRVTITNC LLMNSVTVEE GSNIQGSVIC NNAVIEKGAD 

       430        440        450 
IKDCLIGSGQ RIEAKAKRVN EVIVGNDQLM EI 

« Hide

Isoform 2 [UniParc].

Checksum: 2D3F23DE8D1C6C5A
Show »

FASTA41246,145
Isoform 3 [UniParc].

Checksum: 3D643091793D31BF
Show »

FASTA40144,803

References

« Hide 'large scale' references
[1]"Identification of eIF2B gamma and eIF2 gamma as cofactors of hepatitis C virus internal ribosome entry site-mediated translation using a functional genomics approach."
Krueger M., Beger C., Li Q.-X., Welch P.J., Tritz R., Leavitt M., Barber J.R., Wong-Staal F.
Proc. Natl. Acad. Sci. U.S.A. 97:8566-8571(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Testis.
[3]"The full-ORF clone resource of the German cDNA consortium."
Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U., Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D., Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A., Wiemann S., Schupp I.
BMC Genomics 8:399-399(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
Tissue: Lymph node.
[4]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]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].
[6]"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 3).
Tissue: Blood.
[7]Bienvenut W.V., Boldt K., von Kriegsheim A.F., Kolch W.
Submitted (JUL-2007) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 1-15; 226-234 AND 260-268, ACETYLATION AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Hepatoma.
[8]"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].
[9]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[10]"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 MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"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-87 AND GLN-225.
[12]"Identification of novel EIF2B mutations in Chinese patients with vanishing white matter disease."
Wu Y., Pan Y., Du L., Wang J., Gu Q., Gao Z., Li J., Leng X., Qin J., Wu X., Jiang Y.
J. Hum. Genet. 54:74-77(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VWM GLU-47; GLN-225 AND THR-346.
[13]"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 GLN-27.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF257077 mRNA. Translation: AAF91351.1.
AK024006 mRNA. Translation: BAB14770.1.
AK314668 mRNA. Translation: BAG37225.1.
AL834288 mRNA. Translation: CAD38962.1.
AL136380 Genomic DNA. Translation: CAI23131.1.
AL136380 Genomic DNA. Translation: CAI23132.1.
CH471059 Genomic DNA. Translation: EAX07013.1.
CH471059 Genomic DNA. Translation: EAX07015.1.
BC018728 mRNA. Translation: AAH18728.1.
RefSeqNP_001160060.1. NM_001166588.2.
NP_001248347.1. NM_001261418.1.
NP_065098.1. NM_020365.4.
UniGeneHs.533549.

3D structure databases

ProteinModelPortalQ9NR50.
SMRQ9NR50. Positions 1-131, 307-450.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114408. 30 interactions.
IntActQ9NR50. 5 interactions.
MINTMINT-3072682.
STRING9606.ENSP00000353575.

PTM databases

PhosphoSiteQ9NR50.

Polymorphism databases

DMDM18203317.

2D gel databases

REPRODUCTION-2DPAGEIPI00006504.

Proteomic databases

PaxDbQ9NR50.
PRIDEQ9NR50.

Protocols and materials databases

DNASU8891.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000360403; ENSP00000353575; ENSG00000070785. [Q9NR50-1]
ENST00000372183; ENSP00000361257; ENSG00000070785. [Q9NR50-2]
GeneID8891.
KEGGhsa:8891.
UCSCuc001cmt.3. human. [Q9NR50-1]
uc001cmw.4. human. [Q9NR50-2]

Organism-specific databases

CTD8891.
GeneCardsGC01M045316.
HGNCHGNC:3259. EIF2B3.
HPACAB032233.
HPA024213.
HPA024218.
HPA024219.
MIM603896. phenotype.
606273. gene.
neXtProtNX_Q9NR50.
Orphanet99854. Cree leukoencephalopathy.
157716. Late infantile CACH syndrome.
99853. Ovarioleukodystrophy.
PharmGKBPA27690.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG1208.
HOVERGENHBG051461.
InParanoidQ9NR50.
KOK03241.
OMAEGVKPRT.
PhylomeDBQ9NR50.
TreeFamTF101507.

Enzyme and pathway databases

ReactomeREACT_17015. Metabolism of proteins.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpressQ9NR50.
BgeeQ9NR50.
CleanExHS_EIF2B3.
GenevestigatorQ9NR50.

Family and domain databases

InterProIPR005835. NTP_transferase.
[Graphical view]
PfamPF00483. NTP_transferase. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiEIF2B3.
GenomeRNAi8891.
NextBio33391.
PROQ9NR50.
SOURCESearch...

Entry information

Entry nameEI2BG_HUMAN
AccessionPrimary (citable) accession number: Q9NR50
Secondary accession number(s): B2RBH8 expand/collapse secondary AC list , D3DPZ2, Q5QP89, Q5QP90, Q8NDB5, Q8WV57, Q9H850
Entry history
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: October 1, 2000
Last modified: April 16, 2014
This is version 118 of the entry and version 1 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 1

Human chromosome 1: entries, gene names and cross-references to MIM