O60573 (IF4E2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Eukaryotic translation initiation factor 4E type 2
Short name=eIF-4E type 2
Short name=eIF4E type 2

Alternative name(s):
Eukaryotic translation initiation factor 4E homologous protein
Eukaryotic translation initiation factor 4E-like 3
eIF4E-like protein 4E-LP
mRNA cap-binding protein 4EHP
mRNA cap-binding protein type 3

Gene names

Name:	EIF4E2
Synonyms:	EIF4EL3

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	245 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Recognizes and binds the 7-methylguanosine-containing mRNA cap during an early step in the initiation of protein synthesis and facilitates ribosome binding by inducing the unwinding of the mRNAs secondary structures.
Subunit structure	eIF4F is a multi-subunit complex, the composition of which varies with external and internal environmental conditions. It is composed of at least eIF4A, eIF4E and eIF4G. eIF4E is also known to interact with other partners By similarity. EIF4E2 interacts with EIF4EBP1, EIF4EBP2 and EIF4EBP3 but not with eIF4G. Ref.2
Post-translational modification	Ubiquitinated by ARIH1, leading to its degradation by the proteasome. Ref.5
Sequence similarities	Belongs to the eukaryotic initiation factor 4E family.

Ontologies

Keywords
Biological process	Protein biosynthesis Translation regulation
Ligand	RNA-binding
Molecular function	Initiation factor
PTM	Acetylation Ubl conjugation
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cytokine-mediated signaling pathway Traceable author statement. Source: Reactome negative regulation of translation Inferred from mutant phenotype PubMed 22751931. Source: MGI
Cellular_component	cytosol Traceable author statement. Source: Reactome mRNA cap binding complex Inferred from direct assay Ref.8. Source: UniProtKB
Molecular_function	RNA cap binding Traceable author statement Ref.1. Source: ProtInc translation factor activity, nucleic acid binding Traceable author statement Ref.1. Source: ProtInc translation initiation factor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EIF4ENIF1	Q9NRA8	3	EBI-398610,EBI-301024

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 245

245

Eukaryotic translation initiation factor 4E type 2

PRO_0000193664

Regions

Region

54 – 57

4

EIF4EBP1/2/3 binding

Region

78 – 79

2

7-methylguanosine-containing mRNA cap binding By similarity

Region

95 – 99

5

EIF4EBP1/2/3 binding

Region

124 – 125

2

7-methylguanosine-containing mRNA cap binding

Region

150 – 157

8

EIF4EBP1/2/3 binding

Region

174 – 179

6

7-methylguanosine-containing mRNA cap binding

Region

222 – 224

3

7-methylguanosine-containing mRNA cap binding By similarity

Sites

Binding site

110

1

7-methylguanosine-containing mRNA cap

Amino acid modifications

Modified residue

134

1

N6-acetyllysine Ref.6

Experimental info

Mutagenesis

63

1

W → A: Unable to bind capped mRNA.

Mutagenesis

95

1

W → A: Ability to bind capped mRNA reduced to 40% of wild-type.

Mutagenesis

124 – 126

3

WED → FAA: Unable to bind capped mRNA.

Mutagenesis

124

1

W → A: Ability to bind capped mRNA reduced to less than 10% of wild-type.

Mutagenesis

124

1

W → F: Ability to bind capped mRNA reduced to 13% of wild-type.

Mutagenesis

125

1

E → A: Ability to bind capped mRNA reduced to less than 10% of wild-type.

Mutagenesis

126

1

D → A: Slight reduction in ability to bind capped mRNA.

Mutagenesis

135

1

W → A: Unable to bind capped mRNA.

Mutagenesis

148

1

W → A: Unable to bind capped mRNA.

Mutagenesis

183

1

W → A: Ability to bind capped mRNA reduced to less than 10% of wild-type.

Mutagenesis

183

1

W → F: Unable to bind capped mRNA.

Sequence conflict

1 – 27

27

MNNKF…STQKD → MMTVGTMIRMKKTAHRKI in AAC39871. Ref.3

Secondary structure

1

.

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245

Helix Strand Turn

Details...

Beta strand

55 – 67

13

Helix

75 – 81

7

Beta strand

82 – 90

9

Helix

91 – 98

8

Helix

104 – 106

3

Beta strand

109 – 117

9

Turn

127 – 131

5

Beta strand

133 – 139

7

Helix

144 – 156

13

Beta strand

166 – 173

8

Beta strand

178 – 185

8

Helix

190 – 203

14

Beta strand

212 – 216

5

Helix

217 – 222

6

Sequences

	Sequence		Length	Mass (Da)
	O60573 [UniParc]. Last modified August 1, 1998. Version 1. Checksum: 3D3075BFA48B3C12	FASTA	245	28,362
	10 20 30 40 50 60 MNNKFDALKD DDSGDHDQNE ENSTQKDGEK EKTERDKNQS SSKRKAVVPG PAEHPLQYNY 70 80 90 100 110 120 TFWYSRRTPG RPTSSQSYEQ NIKQIGTFAS VEQFWRFYSH MVRPGDLTGH SDFHLFKEGI 130 140 150 160 170 180 KPMWEDDANK NGGKWIIRLR KGLASRCWEN LILAMLGEQF MVGEEICGAV VSVRFQEDII 190 200 210 220 230 240 SIWNKTASDQ ATTARIRDTL RRVLNLPPNT IMEYKTHTDS IKMPGRLGPQ RLLFQNLWKP RLNVP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and characterization of 4EHP, a novel mammalian eIF4E-related cap-binding protein." Rom E., Kim H.C., Gingras A.-C., Marcotrigiano J., Favre D., Olsen H., Burley S.K., Sonenberg N. J. Biol. Chem. 273:13104-13109(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, 3D-STRUCTURE MODELING, MUTAGENESIS. Tissue: Follicular cell.
[2]	"Characterization of mammalian eIF4E-family members." Joshi B., Cameron A., Jagus R. Eur. J. Biochem. 271:2189-2203(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], INTERACTION WITH EIF4EBP1; EIF4EBP2 AND EIF4EBP3. Tissue: Mammary gland.
[3]	"Identification of genes expressed in human CD34(+) hematopoietic stem/progenitor cells by expressed sequence tags and efficient full-length cDNA cloning." Mao M., Fu G., Wu J.-S., Zhang Q.-H., Zhou J., Kan L.-X., Huang Q.-H., He K.-L., Gu B.-W., Han Z.-G., Shen Y., Gu J., Yu Y.-P., Xu S.-H., Wang Y.-X., Chen S.-J., Chen Z. Proc. Natl. Acad. Sci. U.S.A. 95:8175-8180(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Umbilical cord blood.
[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: Muscle, Urinary bladder and Uterus.
[5]	"Human homologue of ariadne promotes the ubiquitylation of translation initiation factor 4E homologous protein, 4EHP." Tan N.G., Ardley H.C., Scott G.B., Rose S.A., Markham A.F., Robinson P.A. FEBS Lett. 554:501-504(2003) [PubMed] [Europe PMC] [Abstract] Cited for: UBIQUITINATION BY ARIH1.
[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-134, 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]	"Structures of the human eIF4E homologous protein, h4EHP, in its m7GTP-bound and unliganded forms." Rosettani P., Knapp S., Vismara M.-G., Rusconi L., Cameron A.D. J. Mol. Biol. 368:691-705(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 45-234 IN COMPLEX WITH MRNA CAP ANALOGS AND EIF4EBP1.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF047695 mRNA. Translation: AAC18565.1.
AF068117 mRNA. Translation: AAC19374.1.
AF038957 mRNA. Translation: AAC39871.1.
BC005392 mRNA. Translation: AAH05392.1.
BC005874 mRNA. Translation: AAH05874.1.
BC021226 mRNA. Translation: AAH21226.1.
BC021690 mRNA. Translation: AAH21690.1.

IPI

IPI00744211.

RefSeq

NP_004837.1. NM_004846.2.

UniGene

Hs.700929.
Hs.741303.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2JGB	X-ray	1.70	A	45-234	[»]
2JGC	X-ray	2.40	A	45-234	[»]

ProteinModelPortal

O60573.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-32578N.

IntAct

O60573. 11 interactions.

MINT

MINT-1440115.

STRING

9606.ENSP00000258416.

PTM databases

PhosphoSite

O60573.

Proteomic databases

PaxDb

O60573.

PRIDE

O60573.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000258416; ENSP00000258416; ENSG00000135930.

GeneID

9470.

KEGG

hsa:9470.

UCSC

uc002vta.3. human.

Organism-specific databases

CTD

9470.

GeneCards

GC02P233414.

HGNC

HGNC:3293. EIF4E2.

HPA

HPA019253.

MIM

605895. gene.

neXtProt

NX_O60573.

PharmGKB

PA27720.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG5053.

HOGENOM

HOG000186751.

HOVERGEN

HBG107087.

InParanoid

O60573.

KO

K03259.

OMA

IRNQEDI.

OrthoDB

EOG4K0QPD.

PhylomeDB

O60573.

Enzyme and pathway databases

Reactome

REACT_6900. Immune System.

Gene expression databases

ArrayExpress

O60573.

Bgee

O60573.

CleanEx

HS_EIF4E2.

Genevestigator

O60573.

GermOnline

ENSG00000135930. Homo sapiens.

Family and domain databases

Gene3D

3.30.760.10. 1 hit.

InterPro

IPR023398. TIF_eIF4e-like_dom.
IPR001040. TIF_eIF_4E.
IPR019770. TIF_eIF_4E_CS.
[Graphical view]

PANTHER

PTHR11960. PTHR11960. 1 hit.

Pfam

PF01652. IF4E. 1 hit.
[Graphical view]

SUPFAM

SSF55418. TIF_eIF_4E. 1 hit.

PROSITE

PS00813. IF4E. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

EIF4E2. human.

EvolutionaryTrace

O60573.

GenomeRNAi

9470.

NextBio

35490.

SOURCE

Search...

Entry information

Entry name

IF4E2_HUMAN

Accession

Primary (citable) accession number: O60573
Secondary accession number(s): O75349

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 11, 2003
Last sequence update:	August 1, 1998
Last modified:	May 1, 2013
This is version 114 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.