Q9NR50 (EI2BG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Translation initiation factor eIF-2B subunit gamma

Alternative name(s):
eIF-2B GDP-GTP exchange factor subunit gamma

Gene names

Name:

EIF2B3

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	452 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.9 Ref.10 Ref.11
Sequence similarities	Belongs to the eIF-2B gamma/epsilon subunits family.

Ontologies

Keywords
Biological process	Protein biosynthesis
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Leukodystrophy
Molecular function	Initiation factor
PTM	Acetylation
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	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 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 Ref.1PubMed 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	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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 452	452	Translation initiation factor eIF-2B subunit gamma		PRO_0000156079
Amino acid modifications
	Modified residue	1	1	N-acetylmethionine Ref.7
Natural variations
	Alternative sequence	402 – 452	51	SNIQG…QLMEI → YVSPCTHLRQR in isoform 2.		VSP_001436
	Alternative sequence	402 – 452	51	Missing in isoform 3.		VSP_001435
	Natural variant	27	1	L → Q in VWM. Ref.11		VAR_068470
	Natural variant	47	1	G → E in VWM. Ref.10		VAR_068471
	Natural variant	87	1	A → V in VWM. Ref.9		VAR_015409
	Natural variant	225	1	R → Q in VWM. Ref.9 Ref.10		VAR_015410
	Natural variant	288	1	D → E. Corresponds to variant rs3738247 [ dbSNP | Ensembl ].		VAR_048920
	Natural variant	346	1	I → T in VWM. Ref.10		VAR_068472
Experimental info
	Sequence conflict	356	1	S → G in BAB14770. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified October 1, 2000. Version 1. Checksum: 6F73137F59E52773	FASTA	452	50,240
	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
	Isoform 2 [UniParc]. Checksum: 2D3F23DE8D1C6C5A	FASTA	412	46,145
	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 ETQIGEKSSI KRSVIGSSCL IKDRVTITNC LLMNSVTVEE GYVSPCTHLR QR
	Isoform 3 [UniParc]. Checksum: 3D643091793D31BF	FASTA	401	44,803
	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 ETQIGEKSSI KRSVIGSSCL IKDRVTITNC LLMNSVTVEE G

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, 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]	"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.
[10]	"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.
[11]	"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.

Web resources

GeneReviews

Mendelian genes eukaryotic translation initiation factor 2B, subunit 3 gamma, 58kDa (EIF2B3)

Leiden Open Variation Database (LOVD)

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.
IPI	IPI00006504. IPI00217227. IPI00332950.
RefSeq	NP_001160060.1. NM_001166588.2. NP_001248347.1. NM_001261418.1. NP_065098.1. NM_020365.4.
UniGene	Hs.533549.
3D structure databases
ProteinModelPortal	Q9NR50.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9NR50. 5 interactions.
STRING	9606.ENSP00000353575.
PTM databases
PhosphoSite	Q9NR50.
Polymorphism databases
DMDM	18203317.
2D gel databases
REPRODUCTION-2DPAGE	IPI00006504.
Proteomic databases
PaxDb	Q9NR50.
PRIDE	Q9NR50.
Protocols and materials databases
DNASU	8891.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000360403; ENSP00000353575; ENSG00000070785. ENST00000372183; ENSP00000361257; ENSG00000070785.
GeneID	8891.
KEGG	hsa:8891.
UCSC	uc001cmt.2. human. uc001cmw.3. human.
Organism-specific databases
CTD	8891.
GeneCards	GC01M045316.
HGNC	HGNC:3259. EIF2B3.
HPA	HPA024213. HPA024218. HPA024219.
MIM	603896. phenotype. 606273. gene.
neXtProt	NX_Q9NR50.
Orphanet	99854. Cree leukoencephalopathy. 157716. Late infantile CACH syndrome. 99853. Ovarioleukodystrophy.
PharmGKB	PA27690.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1208.
HOVERGEN	HBG051461.
InParanoid	Q9NR50.
KO	K03241.
OMA	TIEEGCN.
OrthoDB	EOG4Q2DFP.
PhylomeDB	Q9NR50.
Enzyme and pathway databases
Reactome	REACT_17015. Metabolism of proteins. REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	Q9NR50.
Bgee	Q9NR50.
CleanEx	HS_EIF2B3.
Genevestigator	Q9NR50.
GermOnline	ENSG00000070785. Homo sapiens.
Family and domain databases
InterPro	IPR005835. NTP_transferase. [Graphical view]
Pfam	PF00483. NTP_transferase. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	8891.
NextBio	33391.
SOURCE	Search...

Entry information

Entry name

EI2BG_HUMAN

Accession

Primary (citable) accession number: Q9NR50
Secondary accession number(s): B2RBH8 , D3DPZ2, Q5QP89, Q5QP90, Q8NDB5, Q8WV57, Q9H850

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 26, 2001
Last sequence update:	October 1, 2000
Last modified:	May 1, 2013
This is version 109 of the entry and version 1 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.