Q9UI10 (EI2BD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

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	523 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.11 Ref.12 Ref.13
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 process	Protein biosynthesis
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Leukodystrophy
Molecular function	Initiation factor
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	myelination Inferred from mutant phenotype PubMed 14566705. Source: UniProtKB 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 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	translation 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 523	523	Translation initiation factor eIF-2B subunit delta		PRO_0000156067
Amino acid modifications
	Modified residue	86	1	Phosphothreonine Ref.7 Ref.8 Ref.9
Natural variations
	Alternative sequence	1 – 10	10	MAAVAVAVRE → MPTQQPAAPSTRAPKPSRSL SGSLCALFSDA in isoform 2.		VSP_001433
	Alternative sequence	71	1	Missing in isoform 2 and isoform 3.		VSP_040130
	Natural variant	93	1	A → V. Corresponds to variant rs34155621 [ dbSNP | Ensembl ].		VAR_048918
	Natural variant	209	1	R → Q in VWM. Ref.13		VAR_068455
	Natural variant	228	1	A → V in VWM. Ref.11		VAR_015405
	Natural variant	269	1	L → R in VWM. Ref.13		VAR_068456
	Natural variant	306	1	R → G. Ref.11		VAR_015406
	Natural variant	357	1	R → Q in VWM. Ref.11		VAR_015407
	Natural variant	374	1	R → C in VWM. Ref.11 Ref.13		VAR_015408
	Natural variant	465	1	C → R in VWM; with ovarian failure. Ref.12		VAR_016843
	Natural variant	489	1	Y → H in VWM; with ovarian failure. Ref.12		VAR_016844
Experimental info
	Sequence conflict	197	1	S → T in CAB57260. Ref.2
	Sequence conflict	197	1	S → T in CAB57261. Ref.2
	Sequence conflict	197	1	S → T in CAB57304. Ref.2
	Sequence conflict	197	1	S → T in CAB57305. Ref.2
	Sequence conflict	323	1	A → S in AAF17195. Ref.1
	Sequence conflict	481	1	S → L in AAF17195. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified February 12, 2003. Version 2. Checksum: 5F38CF10CAD5A45E	FASTA	523	57,557
	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
	Isoform 2 [UniParc]. Checksum: C65253AD9431E074	FASTA	543	59,615
	10 20 30 40 50 60 MPTQQPAAPS TRAPKPSRSL SGSLCALFSD ADSGSGMKAE LPPGPGAVGR EMTKEEKLQL 70 80 90 100 110 120 RKEKKQQKKK RKEEKGAEPE TGSAVSAAQC QGPTRELPES GIQLGTPREK VPAGRSKAEL 130 140 150 160 170 180 RAERRAKQEA ERALKQARKG EQGGPPPKAS PSTAGETPSG VKRLPEYPQV DDLLLRRLVK 190 200 210 220 230 240 KPERQQVPTR KDYGSKVSLF SHLPQYSRQN SLTQFMSIPS SVIHPAMVRL GLQYSQGLVS 250 260 270 280 290 300 GSNARCIALL RALQQVIQDY TTPPNEELSR DLVNKLKPYM SFLTQCRPLS ASMHNAIKFL 310 320 330 340 350 360 NKEITSVGSS KREEEAKSEL RAAIDRYVQE KIVLAAQAIS RFAYQKISNG DVILVYGCSS 370 380 390 400 410 420 LVSRILQEAW TEGRRFRVVV VDSRPWLEGR HTLRSLVHAG VPASYLLIPA ASYVLPEVSK 430 440 450 460 470 480 VLLGAHALLA NGSVMSRVGT AQLALVARAH NVPVLVCCET YKFCERVQTD AFVSNELDDP 490 500 510 520 530 540 DDLQCKRGEH VALANWQNHA SLRLLNLVYD VTPPELVDLV ITELGMIPCS SVPVVLRVKS SDQ
	Isoform 3 [UniParc]. Checksum: D9A7E6FD35CD75F1	FASTA	522	57,458
	10 20 30 40 50 60 MAAVAVAVRE DSGSGMKAEL PPGPGAVGRE MTKEEKLQLR KEKKQQKKKR KEEKGAEPET 70 80 90 100 110 120 GSAVSAAQCQ GPTRELPESG IQLGTPREKV PAGRSKAELR AERRAKQEAE RALKQARKGE 130 140 150 160 170 180 QGGPPPKASP STAGETPSGV KRLPEYPQVD DLLLRRLVKK PERQQVPTRK DYGSKVSLFS 190 200 210 220 230 240 HLPQYSRQNS LTQFMSIPSS VIHPAMVRLG LQYSQGLVSG SNARCIALLR ALQQVIQDYT 250 260 270 280 290 300 TPPNEELSRD LVNKLKPYMS FLTQCRPLSA SMHNAIKFLN KEITSVGSSK REEEAKSELR 310 320 330 340 350 360 AAIDRYVQEK IVLAAQAISR FAYQKISNGD VILVYGCSSL VSRILQEAWT EGRRFRVVVV 370 380 390 400 410 420 DSRPWLEGRH TLRSLVHAGV PASYLLIPAA SYVLPEVSKV LLGAHALLAN GSVMSRVGTA 430 440 450 460 470 480 QLALVARAHN VPVLVCCETY KFCERVQTDA FVSNELDDPD DLQCKRGEHV ALANWQNHAS 490 500 510 520 LRLLNLVYDV TPPELVDLVI TELGMIPCSS VPVVLRVKSS DQ

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[8]	"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, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[9]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"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].
[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-228; GLN-357 AND CYS-374, VARIANT GLY-306.
[12]	"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.
[13]	"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.

Web resources

GeneReviews

Mendelian genes eukaryotic translation initiation factor 2B, subunit 4 delta, 67kDa (EIF2B4)

Leiden Open Variation Database (LOVD)

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.
IPI	IPI00005979. IPI00220232. IPI00654843.
RefSeq	NP_001029288.1. NM_001034116.1. NP_056451.3. NM_015636.3. NP_751945.2. NM_172195.3.
UniGene	Hs.169474.
3D structure databases
ProteinModelPortal	Q9UI10.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UI10. 4 interactions.
STRING	9606.ENSP00000394869.
PTM databases
PhosphoSite	Q9UI10.
Polymorphism databases
DMDM	28381357.
Proteomic databases
PaxDb	Q9UI10.
PRIDE	Q9UI10.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000347454; ENSP00000233552; ENSG00000115211. ENST00000445933; ENSP00000394397; ENSG00000115211. ENST00000451130; ENSP00000394869; ENSG00000115211.
GeneID	8890.
KEGG	hsa:8890.
UCSC	uc002rjz.3. human. uc002rka.3. human. uc002rkc.3. human.
Organism-specific databases
CTD	8890.
GeneCards	GC02M027587.
HGNC	HGNC:3260. EIF2B4.
HPA	CAB032234.
MIM	603896. phenotype. 606687. gene.
neXtProt	NX_Q9UI10.
Orphanet	99854. Cree leukoencephalopathy. 157716. Late infantile CACH syndrome. 99853. Ovarioleukodystrophy.
PharmGKB	PA27691.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1184.
HOGENOM	HOG000176924.
HOVERGEN	HBG051459.
InParanoid	Q9UI10.
KO	K03680.
Enzyme and pathway databases
Reactome	REACT_17015. Metabolism of proteins. REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	Q9UI10.
Bgee	Q9UI10.
CleanEx	HS_EIF2B4.
Genevestigator	Q9UI10.
GermOnline	ENSG00000115211. 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	8890.
NextBio	33383.
SOURCE	Search...

Entry information

Entry name

EI2BD_HUMAN

Accession

Primary (citable) accession number: Q9UI10
Secondary accession number(s): Q53RY7 , Q5BJF4, Q9BUV9, Q9UBG4, Q9UIQ9, Q9UJ95

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	February 12, 2003
Last modified:	May 1, 2013
This is version 113 of the entry and version 2 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.