Reviewed, UniProtKB/Swiss-Prot Q13541 (4EBP1_HUMAN)

Names and origin

Protein names

Recommended name:
    Eukaryotic translation initiation factor 4E-binding protein 1
      Short name=eIF4E-binding protein 1
      Short name=4E-BP1
Alternative name(s):
    Phosphorylated heat- and acid-stable protein regulated by insulin 1
      Short name=PHAS-I

Gene names

Name:

EIF4EBP1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	118 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Regulates eIF4E activity by preventing its assembly into the eIF4F complex. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase pathway. Ref.1
Subunit structure	Nonphosphorylated EIF4EBP1 competes with EIF4G1/EIF4G3 to interact with EIF4E; insulin stimulated MAP-kinase (MAPK1 and MAPK3) phosphorylation of EIF4EBP1 causes dissociation of the complex allowing EIF4G1/EIF4G3 to bind and consequent initiation of translation. Rapamycin can attenuate insulin stimulation, mediated by FKBPs.
Post-translational modification	Phosphorylated on serine and threonine residues in response to insulin, EGF and PDGF. Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.1 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14
Sequence similarities	Belongs to the eIF4E-binding protein family.

Ontologies

Keywords
Biological process	Translation regulation
Molecular function	Protein synthesis inhibitor
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Cellular component	cytosol Ref.1 Inferred from Experiment. Source: Reactome
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
EIF4E	P06730	4	EBI-74090,EBI-73440
EIF4E2	O60573	1	EBI-74090,EBI-398610
Eif4e2	Q80ZJ3	1	EBI-74090,EBI-934970	From a different organism.
UBAC1	Q9BSL1	1	EBI-74090,EBI-749370

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.6

Chain

2 – 118

117

Eukaryotic translation initiation factor 4E-binding protein 1

PRO_0000190513

Amino acid modifications

Modified residue

2

1

N-acetylserine Ref.6 UniProtKB Q62622

Modified residue

35

1

Phosphoserine Ref.13

Modified residue

36

1

Phosphothreonine Ref.13

Modified residue

37

1

Phosphothreonine Ref.13 Ref.14

Modified residue

41

1

Phosphothreonine Ref.13 Ref.14

Modified residue

46

1

Phosphothreonine Ref.9 Ref.13 Ref.14

Modified residue

50

1

Phosphothreonine Ref.13 Ref.14

Modified residue

54

1

Phosphotyrosine Ref.14

Modified residue

65

1

Phosphoserine; by MAPK1 and MAPK3 Ref.8 Ref.10 Ref.12 Ref.14 UniProtKB Q62622

Modified residue

68

1

Phosphothreonine Ref.12

Modified residue

70

1

Phosphothreonine Ref.10 Ref.13 Ref.14

Modified residue

77

1

Phosphothreonine Ref.14

Modified residue

82

1

Phosphothreonine Ref.13

Modified residue

83

1

Phosphoserine Ref.13 Ref.14

Modified residue

94

1

Phosphoserine Ref.10 Ref.13 Ref.14

Modified residue

101

1

Phosphoserine Ref.10 Ref.13

Modified residue

112

1

Phosphoserine Ref.11

Secondary structure

1

.

.

.

118

Helix Strand Turn

Details...

Helix

56 – 61

6

Sequences

	Sequence		Length	Mass (Da)
	Q13541-1 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 1682A6BA74132966	FASTA	118	12,580
	10 20 30 40 50 60 MSGGSSCSQT PSRAIPATRR VVLGDGVQLP PGDYSTTPGG TLFSTTPGGT RIIYDRKFLM 70 80 90 100 110 ECRNSPVTKT PPRDLPTIPG VTSPSSDEPP MEASQSHLRN SPEDKRAGGE ESQFEMDI

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5'-cap function." Pause A., Belsham G.J., Gingras A.-C., Donze O., Lin T.-A., Lawrence J.C. Jr., Sonenberg N. Nature 371:762-767(1994) [PubMed: 7935836] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH EIF4E, PHOSPHORYLATION. Tissue: Placenta.
[2]	"Identification of multiple genes and immunogenic epitopes of pancreatic cancer cells." Ito M., Shichijo S., Tsuda N., Ochi M., Harashima N., Saito N., Itoh K. Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]	"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].
[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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon and Lung.
[6]	"Exploring proteomes and analyzing protein processing by mass spectrometric identification of sorted N-terminal peptides." Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., Vandekerckhove J. Nat. Biotechnol. 21:566-569(2003) [PubMed: 12665801] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-13, ACETYLATION AT SER-2. Tissue: Platelet.
[7]	"Repression of cap-dependent translation by 4E-binding protein 1: competition with p220 for binding to eukaryotic initiation factor-4E." Haghighat A., Mader S., Pause A., Sonenberg N. EMBO J. 14:5701-5709(1995) [PubMed: 8521827] [Abstract] Cited for: INTERACTION WITH EIF4E AND EIF4G.
[8]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65, MASS SPECTROMETRY. Tissue: Epithelium.
[9]	"Toward a global characterization of the phosphoproteome in prostate cancer cells: identification of phosphoproteins in the LNCaP cell line." Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S. Electrophoresis 28:2027-2034(2007) [PubMed: 17487921] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-46, MASS SPECTROMETRY.
[10]	"Global proteomic profiling of phosphopeptides using electron transfer dissociation tandem mass spectrometry." Molina H., Horn D.M., Tang N., Mathivanan S., Pandey A. Proc. Natl. Acad. Sci. U.S.A. 104:2199-2204(2007) [PubMed: 17287340] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65; THR-70; SER-94 AND SER-101, MASS SPECTROMETRY.
[11]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-112, MASS SPECTROMETRY.
[12]	"Automated phosphoproteome analysis for cultured cancer cells by two-dimensional nanoLC-MS using a calcined titania/C18 biphasic column." Imami K., Sugiyama N., Kyono Y., Tomita M., Ishihama Y. Anal. Sci. 24:161-166(2008) [PubMed: 18187866] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65 AND THR-68, MASS SPECTROMETRY.
[13]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-35; THR-36; THR-37; THR-41; THR-46; THR-50; THR-70; THR-82; SER-83; SER-94 AND SER-101, MASS SPECTROMETRY.
[14]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-37; THR-41; THR-46; THR-50; TYR-54; SER-65; THR-70; THR-77; SER-83 AND SER-94, MASS SPECTROMETRY.
[15]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[16]	"The interaction of eIF4E with 4E-BP1 is an induced fit to a completely disordered protein." Fletcher C.M., Wagner G. Protein Sci. 7:1639-1642(1998) [PubMed: 9684899] [Abstract] Cited for: STRUCTURE BY NMR OF 4-118.
[17]	"Structural basis for mRNA cap-binding regulation of eukaryotic initiation factor 4E by 4E-binding protein, studied by spectroscopic, X-ray crystal structural, and molecular dynamics simulation methods." Tomoo K., Matsushita Y., Fujisaki H., Abiko F., Shen X., Taniguchi T., Miyagawa H., Kitamura K., Miura K., Ishida T. Biochim. Biophys. Acta 1753:191-208(2005) [PubMed: 16271312] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 36-70 IN COMPLEX WITH EIF4E AND MRNA CAP ANALOG.
[18]	"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: 17368478] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 51-67 IN COMPLEX WITH EIF4E2 AND MRNA CAP ANALOG.
[19]	"Crystallographic and mass spectrometric characterisation of eIF4E with N7-alkylated cap derivatives." Brown C.J., McNae I., Fischer P.M., Walkinshaw M.D. J. Mol. Biol. 372:7-15(2007) [PubMed: 17631896] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 51-64 IN COMPLEX WITH EIF4E AND MRNA CAP ANALOG.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

L36055 mRNA. Translation: AAA62269.1.
AB044548 mRNA. Translation: BAB18650.1.
BT007162 mRNA. Translation: AAP35826.1.
CR456769 mRNA. Translation: CAG33050.1.
BC004459 mRNA. Translation: AAH04459.1.
BC058073 mRNA. Translation: AAH58073.1.

IPI

IPI00002569.

PIR

S50866.

RefSeq

NP_004086.1.

UniGene

Hs.411641

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1WKW	X-ray	2.10	B	47-66	[»]
2JGB	X-ray	1.70	B	51-67	[»]
2JGC	X-ray	2.40	B	51-67	[»]
2V8W	X-ray	2.30	B/F	51-64	[»]
2V8X	X-ray	2.30	B/F	51-64	[»]
2V8Y	X-ray	2.10	B/F	51-64	[»]

DisProt

DP00028.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q13541. 10 interactions.

PTM databases

PhosphoSite

Q13541.

Proteomic databases

PeptideAtlas

Q13541.

PRIDE

Q13541.

Genome annotation databases

Ensembl

ENSG00000187840. Homo sapiens. [Contig view]

GeneID

1978.

KEGG

hsa:1978.

Organism-specific databases

GeneCards

GC08P038007.

H-InvDB

HIX0004694.

HGNC

HGNC:3288. EIF4EBP1.

HPA

CAB005032.
CAB005039.

MIM

602223. gene.

PharmGKB

PA27715.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

Q13541.

HOVERGEN

Q13541.

OMA

Q13541. DKPAGGE.

Enzyme and pathway databases

Pathway_Interaction_DB

insulin_pathway. Insulin Pathway.
mtor_4pathway. mTOR signaling pathway.
p38alphabetadownstreampathway. Signaling mediated by p38-alpha and p38-beta.

Reactome

REACT_498. Signaling by Insulin receptor.
REACT_71. Gene Expression.

Gene expression databases

ArrayExpress

Q13541.

Bgee

Q13541.

CleanEx

HS_EIF4EBP1.

GermOnline

ENSG00000187840. Homo sapiens.

Family and domain databases

InterPro

IPR008606. EIF4EBP.
[Graphical view]

PANTHER

PTHR12669. EIF4EBP. 1 hit.

Pfam

PF05456. eIF_4EBP. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

8003.

PMAP-CutDB

Q13541.

SOURCE

Search...

Entry information

Entry name

4EBP1_HUMAN

Accession

Primary (citable) accession number: Q13541
Secondary accession number(s): Q6IBN3

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2003
Last sequence update:	January 23, 2007
Last modified:	June 16, 2009
This is version 84 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)