Q14232 (EI2BA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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

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

Gene names

Name:	EIF2B1
Synonyms:	EIF2BA

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	305 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.8 Ref.9
Sequence similarities	Belongs to the eIF-2B alpha/beta/delta subunits family.

Ontologies

Keywords
Biological process	Protein biosynthesis
Disease	Disease mutation Leukodystrophy
Molecular function	Initiation factor
PTM	Acetylation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to stimulus Inferred from direct assay PubMed 8626696. Source: UniProtKB negative regulation of translational initiation in response to stress Inferred from electronic annotation. Source: Compara oligodendrocyte development Inferred from mutant phenotype PubMed 15217090. Source: UniProtKB regulation of translational initiation Inferred from Biological aspect of Ancestor. Source: RefGenome 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 plasma membrane Inferred from direct assay PubMed 9235896. Source: MGI
Molecular_function	GDP binding Inferred from electronic annotation. Source: Compara GTP binding Inferred from electronic annotation. Source: Compara enzyme regulator activity Inferred from electronic annotation. Source: Compara translation initiation factor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Adra2a	Q01338	2	EBI-491065,EBI-491073	From a different organism.
Adra2b	P30545	2	EBI-491065,EBI-491084	From a different organism.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 305

305

Translation initiation factor eIF-2B subunit alpha

PRO_0000156055

Amino acid modifications

Modified residue

35

1

N6-acetyllysine Ref.6

Natural variations

Natural variant

183

1

V → F in VWM. Ref.9

VAR_068450

Natural variant

208

1

N → Y in VWM. Ref.8

VAR_015404

Secondary structure

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305

Helix Strand Turn

Details...

Helix

3 – 16

14

Helix

22 – 34

13

Helix

44 – 54

11

Turn

55 – 59

5

Helix

63 – 75

13

Helix

92 – 104

13

Helix

107 – 115

9

Helix

116 – 118

3

Beta strand

123 – 127

5

Helix

132 – 142

11

Turn

143 – 145

3

Beta strand

148 – 153

6

Turn

156 – 159

4

Helix

160 – 169

10

Turn

170 – 172

3

Beta strand

175 – 178

4

Helix

180 – 182

3

Helix

183 – 186

4

Helix

187 – 189

3

Beta strand

191 – 196

6

Beta strand

198 – 200

3

Beta strand

206 – 209

4

Helix

212 – 221

10

Beta strand

226 – 229

4

Helix

232 – 234

3

Helix

243 – 245

3

Helix

248 – 250

3

Beta strand

272 – 276

5

Helix

278 – 280

3

Beta strand

282 – 286

5

Beta strand

289 – 291

3

Helix

293 – 295

3

Helix

296 – 304

9

Sequences

	Sequence		Length	Mass (Da)
	Q14232 [UniParc]. Last modified November 1, 1997. Version 1. Checksum: 91A915FF1B80B780	FASTA	305	33,712
	10 20 30 40 50 60 MDDKELIEYF KSQMKEDPDM ASAVAAIRTL LEFLKRDKGE TIQGLRANLT SAIETLCGVD 70 80 90 100 110 120 SSVAVSSGGE LFLRFISLAS LEYSDYSKCK KIMIERGELF LRRISLSRNK IADLCHTFIK 130 140 150 160 170 180 DGATILTHAY SRVVLRVLEA AVAAKKRFSV YVTESQPDLS GKKMAKALCH LNVPVTVVLD 190 200 210 220 230 240 AAVGYIMEKA DLVIVGAEGV VENGGIINKI GTNQMAVCAK AQNKPFYVVA ESFKFVRLFP 250 260 270 280 290 300 LNQQDVPDKF KYKADTLKVA QTGQDLKEEH PWVDYTAPSL ITLLFTDLGV LTPSAVSDEL IKLYL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	Torp A. Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[3]	"The finished DNA sequence of human chromosome 12." Scherer S.E., Muzny D.M., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R. , Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Montgomery K.T., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Lovering R.C., Wheeler D.A., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clerc-Blankenburg K.P., Davis C., Delgado O., Dinh H.H., Draper H., Gonzalez-Garay M.L., Havlak P., Jackson L.R., Jacob L.S., Kelly S.H., Li L., Li Z., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Pasternak S., Perez L.M., Plopper F.J.H., Santibanez J., Shen H., Tabor P.E., Verduzco D., Waldron L., Wang Q., Williams G.A., Zhang J., Zhou J., Allen C.C., Amin A.G., Anyalebechi V., Bailey M., Barbaria J.A., Bimage K.E., Bryant N.P., Burch P.E., Burkett C.E., Burrell K.L., Calderon E., Cardenas V., Carter K., Casias K., Cavazos I., Cavazos S.R., Ceasar H., Chacko J., Chan S.N., Chavez D., Christopoulos C., Chu J., Cockrell R., Cox C.D., Dang M., Dathorne S.R., David R., Davis C.M., Davy-Carroll L., Deshazo D.R., Donlin J.E., D'Souza L., Eaves K.A., Egan A., Emery-Cohen A.J., Escotto M., Flagg N., Forbes L.D., Gabisi A.M., Garza M., Hamilton C., Henderson N., Hernandez O., Hines S., Hogues M.E., Huang M., Idlebird D.G., Johnson R., Jolivet A., Jones S., Kagan R., King L.M., Leal B., Lebow H., Lee S., LeVan J.M., Lewis L.C., London P., Lorensuhewa L.M., Loulseged H., Lovett D.A., Lucier A., Lucier R.L., Ma J., Madu R.C., Mapua P., Martindale A.D., Martinez E., Massey E., Mawhiney S., Meador M.G., Mendez S., Mercado C., Mercado I.C., Merritt C.E., Miner Z.L., Minja E., Mitchell T., Mohabbat F., Mohabbat K., Montgomery B., Moore N., Morris S., Munidasa M., Ngo R.N., Nguyen N.B., Nickerson E., Nwaokelemeh O.O., Nwokenkwo S., Obregon M., Oguh M., Oragunye N., Oviedo R.J., Parish B.J., Parker D.N., Parrish J., Parks K.L., Paul H.A., Payton B.A., Perez A., Perrin W., Pickens A., Primus E.L., Pu L.-L., Puazo M., Quiles M.M., Quiroz J.B., Rabata D., Reeves K., Ruiz S.J., Shao H., Sisson I., Sonaike T., Sorelle R.P., Sutton A.E., Svatek A.F., Svetz L.A., Tamerisa K.S., Taylor T.R., Teague B., Thomas N., Thorn R.D., Trejos Z.Y., Trevino B.K., Ukegbu O.N., Urban J.B., Vasquez L.I., Vera V.A., Villasana D.M., Wang L., Ward-Moore S., Warren J.T., Wei X., White F., Williamson A.L., Wleczyk R., Wooden H.S., Wooden S.H., Yen J., Yoon L., Yoon V., Zorrilla S.E., Nelson D., Kucherlapati R., Weinstock G., Gibbs R.A. Nature 440:346-351(2006) [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 (JUL-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].
[6]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-35, MASS SPECTROMETRY.
[7]	"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].
[8]	"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: VARIANT VWM TYR-208.
[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: VARIANT VWM PHE-183.
+	Additional computationally mapped references.

Web resources

GeneReviews

Mendelian genes eukaryotic translation initiation factor 2B, subunit 1 alpha, 26kDa (EIF2B1)

Leiden Open Variation Database (LOVD)

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X95648 mRNA. Translation: CAA64950.1.
CR456831 mRNA. Translation: CAG33112.1.
AC117503 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW98424.1.
BC103763 mRNA. Translation: AAI03764.1.
BC104188 mRNA. Translation: AAI04189.1.
BC104189 mRNA. Translation: AAI04190.1.

IPI

IPI00221300.

RefSeq

NP_001405.1. NM_001414.3.

UniGene

Hs.741273.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3ECS	X-ray	2.65	A/B/C/D/E/F/G/H	1-305	[»]

ProteinModelPortal

Q14232.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q14232. 19 interactions.

MINT

MINT-1412710.

STRING

9606.ENSP00000228958.

PTM databases

PhosphoSite

Q14232.

Polymorphism databases

DMDM

2494303.

Proteomic databases

PaxDb

Q14232.

PRIDE

Q14232.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000424014; ENSP00000416250; ENSG00000111361.

GeneID

1967.

KEGG

hsa:1967.

UCSC

uc001ufm.3. human.

Organism-specific databases

CTD

1967.

GeneCards

GC12M124105.

HGNC

HGNC:3257. EIF2B1.

HPA

CAB034258.

MIM

603896. phenotype.
606686. gene.

neXtProt

NX_Q14232.

Orphanet

99854. Cree leukoencephalopathy.
157716. Late infantile CACH syndrome.
99853. Ovarioleukodystrophy.

PharmGKB

PA27688.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1184.

HOGENOM

HOG000175731.

HOVERGEN

HBG051457.

InParanoid

Q14232.

KO

K03239.

OMA

HPLVDYT.

OrthoDB

EOG4K9BCT.

Enzyme and pathway databases

Reactome

REACT_17015. Metabolism of proteins.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

Q14232.

Bgee

Q14232.

CleanEx

HS_EIF2B1.

Genevestigator

Q14232.

GermOnline

ENSG00000111361. 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

EvolutionaryTrace

Q14232.

GenomeRNAi

1967.

NextBio

7975.

SOURCE

Search...

Entry information

Entry name

EI2BA_HUMAN

Accession

Primary (citable) accession number: Q14232
Secondary accession number(s): A6NLY9, Q3SXP4

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	November 1, 1997
Last modified:	May 1, 2013
This is version 110 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.