dbPTM

4EBP1_HUMAN - PTM Information in dbPTM

Basic Information of Protein

Overview of Protein Modification Sites with Functional and Structural Information
UniProt ID	4EBP1_HUMAN
UniProt AC	Q13541
Protein Name	Eukaryotic translation initiation factor 4E-binding protein 1
Gene Name	EIF4EBP1
Organism	Homo sapiens (Human).
Sequence Length	118
Subcellular Localization
Protein Description	Repressor of translation initiation that regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form competes with EIF4G1/EIF4G3 and strongly binds to EIF4E, leading to repress translation. In contrast, hyperphosphorylated form dissociates from EIF4E, allowing interaction between EIF4G1/EIF4G3 and EIF4E, leading to initiation of translation. Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways..
Protein Sequence	MSGGSSCSQTPSRAIPATRRVVLGDGVQLPPGDYSTTPGGTLFSTTPGGTRIIYDRKFLMECRNSPVTKTPPRDLPTIPGVTSPSSDEPPMEASQSHLRNSPEDKRAGGEESQFEMDI

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Acetylation	------MSGGSSCSQ ------CCCCCCCCC	52.43	22814378
2	Phosphorylation	------MSGGSSCSQ ------CCCCCCCCC	52.43	29255136
5	Phosphorylation	---MSGGSSCSQTPS ---CCCCCCCCCCCC	31.53	29255136
6	Phosphorylation	--MSGGSSCSQTPSR --CCCCCCCCCCCCC	22.51	23663014
8	Phosphorylation	MSGGSSCSQTPSRAI CCCCCCCCCCCCCCC	38.75	23663014
10	Phosphorylation	GGSSCSQTPSRAIPA CCCCCCCCCCCCCCC	13.62	23663014
12	Phosphorylation	SSCSQTPSRAIPATR CCCCCCCCCCCCCCC	37.42	25849741
18	Phosphorylation	PSRAIPATRRVVLGD CCCCCCCCCEEEECC	17.41	23663014
34	Phosphorylation	VQLPPGDYSTTPGGT CCCCCCCCCCCCCCC	17.52	22322096
35	Phosphorylation	QLPPGDYSTTPGGTL CCCCCCCCCCCCCCE	30.46	22322096
36	Phosphorylation	LPPGDYSTTPGGTLF CCCCCCCCCCCCCEE	30.68	22322096
37	Phosphorylation	PPGDYSTTPGGTLFS CCCCCCCCCCCCEEE	17.62	22039466
41	Phosphorylation	YSTTPGGTLFSTTPG CCCCCCCCEEECCCC	30.46	22322096
44	Phosphorylation	TPGGTLFSTTPGGTR CCCCCEEECCCCCEE	34.19	22322096
45	Phosphorylation	PGGTLFSTTPGGTRI CCCCEEECCCCCEEE	29.67	22322096
46	Phosphorylation	GGTLFSTTPGGTRII CCCEEECCCCCEEEE	20.81	22039466
50	Phosphorylation	FSTTPGGTRIIYDRK EECCCCCEEEEEECC	25.30	22322096
54	Phosphorylation	PGGTRIIYDRKFLME CCCEEEEEECCCHHH	13.81	22322096
57	Acetylation	TRIIYDRKFLMECRN EEEEEECCCHHHHCC	39.70	27452117
57	Ubiquitination	TRIIYDRKFLMECRN EEEEEECCCHHHHCC	39.70	PubMed
62	S-nitrosylation	DRKFLMECRNSPVTK ECCCHHHHCCCCCCC	2.88	24105792
63	Methylation	RKFLMECRNSPVTKT CCCHHHHCCCCCCCC	33.10	-
65	Phosphorylation	FLMECRNSPVTKTPP CHHHHCCCCCCCCCC	11.03	29255136
68	Phosphorylation	ECRNSPVTKTPPRDL HHCCCCCCCCCCCCC	32.36	29255136
68	O-linked_Glycosylation	ECRNSPVTKTPPRDL HHCCCCCCCCCCCCC	32.36	23301498
69	Ubiquitination	CRNSPVTKTPPRDLP HCCCCCCCCCCCCCC	60.30	PubMed
69	Phosphoglycerylation	CRNSPVTKTPPRDLP HCCCCCCCCCCCCCC	60.30	-
70	Phosphorylation	RNSPVTKTPPRDLPT CCCCCCCCCCCCCCC	29.20	29255136
77	Phosphorylation	TPPRDLPTIPGVTSP CCCCCCCCCCCCCCC	47.29	29255136
82	Phosphorylation	LPTIPGVTSPSSDEP CCCCCCCCCCCCCCC	40.61	29255136
83	Phosphorylation	PTIPGVTSPSSDEPP CCCCCCCCCCCCCCC	22.00	29255136
85	Phosphorylation	IPGVTSPSSDEPPME CCCCCCCCCCCCCCH	50.63	29255136
86	Phosphorylation	PGVTSPSSDEPPMEA CCCCCCCCCCCCCHH	49.75	29255136
94	Phosphorylation	DEPPMEASQSHLRNS CCCCCHHHHHHHHCC	20.93	29255136
96	Phosphorylation	PPMEASQSHLRNSPE CCCHHHHHHHHCCHH	23.22	29255136
101	Phosphorylation	SQSHLRNSPEDKRAG HHHHHHCCHHHHHCC	24.19	29255136
105	Ubiquitination	LRNSPEDKRAGGEES HHCCHHHHHCCCCCH	42.35	PubMed
112	Phosphorylation	KRAGGEESQFEMDI- HHCCCCCHHCCCCC-	35.55	17525332
116	Sulfoxidation	GEESQFEMDI----- CCCHHCCCCC-----	6.24	21406390

Upstream regulatory proteins (kinases for phosphorylation sites, E3 ubiquitin ligases of ubiquitination sites, ...)

Modified Location	Modified Residue	Modification	Type of Upstream Proteins	Gene Name of Upstream Proteins	UniProt AC of Upstream Proteins	Sources
8	S	Phosphorylation	Kinase	ATM	Q13315	PhosphoELM
36	T	Phosphorylation	Kinase	MTOR	P42345	GPS
37	T	Phosphorylation	Kinase	MTOR	P42346	PSP
37	T	Phosphorylation	Kinase	MTOR	Q9JLN9	PSP
37	T	Phosphorylation	Kinase	GSK3B	P49841	PSP
37	T	Phosphorylation	Kinase	MTOR	P42345	Uniprot
37	T	Phosphorylation	Kinase	MAPK1	P28482	GPS
41	T	Phosphorylation	Kinase	MTOR	P42345	PSP
41	T	Phosphorylation	Kinase	CSNK1E	P49674	GPS
44	S	Phosphorylation	Kinase	MTOR	P42345	PSP
45	T	Phosphorylation	Kinase	MTOR	P42345	GPS
46	T	Phosphorylation	Kinase	MTOR	P42346	PSP
46	T	Phosphorylation	Kinase	MTOR	Q9JLN9	PSP
46	T	Phosphorylation	Kinase	MTOR	P42345	Uniprot
46	T	Phosphorylation	Kinase	MAPK1	P28482	GPS
46	T	Phosphorylation	Kinase	GSK3B	P49841	PSP
50	T	Phosphorylation	Kinase	CSNK1E	P49674	GPS
65	S	Phosphorylation	Kinase	ERK1	P27361	PSP
65	S	Phosphorylation	Kinase	MTOR	P42345	Uniprot
65	S	Phosphorylation	Kinase	GSK3B	P49841	PSP
65	S	Phosphorylation	Kinase	ERK2	P28482	PSP
65	S	Phosphorylation	Kinase	DYRK2	Q92630	Uniprot
65	S	Phosphorylation	Kinase	MTOR	Q9JLN9	PSP
70	T	Phosphorylation	Kinase	MAP3K8	P41279	GPS
70	T	Phosphorylation	Kinase	MAPK1	P28482	GPS
70	T	Phosphorylation	Kinase	GSK3B	P49841	PSP
70	T	Phosphorylation	Kinase	MTOR	P42345	Uniprot
70	T	Phosphorylation	Kinase	CDK1	P06493	PSP
83	S	Phosphorylation	Kinase	MTOR	P42345	PhosphoELM
83	S	Phosphorylation	Kinase	CDK1	P06493	PSP
94	S	Phosphorylation	Kinase	ATM	Q13315	PSP
101	S	Phosphorylation	Kinase	MTOR	P42345	PhosphoELM
101	S	Phosphorylation	Kinase	DYRK2	Q92630	Uniprot
112	S	Phosphorylation	Kinase	CSNK2A1	P68400	GPS
112	S	Phosphorylation	Kinase	ATM	Q13315	PhosphoELM
-	K	Ubiquitination	E3 ubiquitin ligase	KLHL25	Q9H0H3	PMID:22578813

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Reference
37	T	Phosphorylation	12747827
Not ubiquitinated when hyperphosphorylated (at Thr-37, Thr-46, Ser-65 and Thr-70) or associated with eIF4E.
37	T	Phosphorylation	12747827
Phosphorylation at Thr-37, Thr-46, Ser-65 and Thr-70, corresponding to the hyperphosphorylated form, is regulated by mTORC1 and abolishes binding to EIF4E.
37	T	ubiquitylation	12747827
Not ubiquitinated when hyperphosphorylated (at Thr-37, Thr-46, Ser-65 and Thr-70) or associated with eIF4E.
46	T	Phosphorylation	12747827
Not ubiquitinated when hyperphosphorylated (at Thr-37, Thr-46, Ser-65 and Thr-70) or associated with eIF4E.
46	T	Phosphorylation	12747827
Phosphorylation at Thr-37, Thr-46, Ser-65 and Thr-70, corresponding to the hyperphosphorylated form, is regulated by mTORC1 and abolishes binding to EIF4E.
46	T	ubiquitylation	12747827
Not ubiquitinated when hyperphosphorylated (at Thr-37, Thr-46, Ser-65 and Thr-70) or associated with eIF4E.
65	S	Phosphorylation	12747827
Not ubiquitinated when hyperphosphorylated (at Thr-37, Thr-46, Ser-65 and Thr-70) or associated with eIF4E.
65	S	Phosphorylation	12747827
Phosphorylation at Thr-37, Thr-46, Ser-65 and Thr-70, corresponding to the hyperphosphorylated form, is regulated by mTORC1 and abolishes binding to EIF4E.
65	S	ubiquitylation	12747827
Not ubiquitinated when hyperphosphorylated (at Thr-37, Thr-46, Ser-65 and Thr-70) or associated with eIF4E.
70	T	Phosphorylation	12747827
Not ubiquitinated when hyperphosphorylated (at Thr-37, Thr-46, Ser-65 and Thr-70) or associated with eIF4E.
70	T	Phosphorylation	12747827
Phosphorylation at Thr-37, Thr-46, Ser-65 and Thr-70, corresponding to the hyperphosphorylated form, is regulated by mTORC1 and abolishes binding to EIF4E.
70	T	ubiquitylation	12747827
Not ubiquitinated when hyperphosphorylated (at Thr-37, Thr-46, Ser-65 and Thr-70) or associated with eIF4E.

Disease-associated PTM Sites based on SAP

* Distance = the distance between SAP position and PTM sites.

Modified Location	Modification	Variant Position (Distance <= 10)	Residue Change	SAP	Related Disease	Reference
Oops, there are no SNP-PTM records of 4EBP1_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
CTF8_HUMAN	CHTF8	physical	16189514
UBAC1_HUMAN	UBAC1	physical	17353931
IF4E_HUMAN	EIF4E	physical	17353931
IF4E_HUMAN	EIF4E	physical	16242075
IF4E_HUMAN	EIF4E	physical	16824195
IF4E_HUMAN	EIF4E	physical	10405182
MTOR_HUMAN	MTOR	physical	12150926
MTOR_HUMAN	MTOR	physical	16798736
MTOR_HUMAN	MTOR	physical	15767663
RPTOR_HUMAN	RPTOR	physical	12912989
RPTOR_HUMAN	RPTOR	physical	12747827
RPTOR_HUMAN	RPTOR	physical	12150926
RPTOR_HUMAN	RPTOR	physical	16798736
RPTOR_HUMAN	RPTOR	physical	15767663
RPTOR_HUMAN	RPTOR	physical	12604610
IF4E_HUMAN	EIF4E	physical	11605658
IF4E_HUMAN	EIF4E	physical	18957614
KLH25_HUMAN	KLHL25	physical	22578813
IF4E_HUMAN	EIF4E	physical	16798736
IF4E_HUMAN	EIF4E	physical	15767663
RPTOR_HUMAN	RPTOR	physical	17502379
RPTOR_HUMAN	RPTOR	physical	18337751
REL_HUMAN	REL	physical	25416956
ITF2_HUMAN	TCF4	physical	25416956
ROAA_HUMAN	HNRNPAB	physical	26344197
IF4E_HUMAN	EIF4E	physical	12747804

Drug and Disease Associations

Kegg Disease
There are no disease associations of PTM sites.
OMIM Disease
There are no disease associations of PTM sites.
Kegg Drug
There are no disease associations of PTM sites.
DrugBank
There are no disease associations of PTM sites.

Regulatory Network of 4EBP1_HUMAN

Related Literatures of Post-Translational Modification

Acetylation
Reference	PubMed
"Exploring proteomes and analyzing protein processing by massspectrometric 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). Cited for: PROTEIN SEQUENCE OF 2-13, AND ACETYLATION AT SER-2.	12665801 [Abstract]
Phosphorylation
Reference	PubMed
"Lys-N and trypsin cover complementary parts of the phosphoproteome ina refined SCX-based approach."; Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,Mohammed S.; Anal. Chem. 81:4493-4501(2009). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-10; TYR-34; THR-37;THR-41; SER-44; THR-45 AND THR-46, AND MASS SPECTROMETRY.	19413330 [Abstract]
"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). 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, AND MASSSPECTROMETRY.	18669648 [Abstract]
"Combining protein-based IMAC, peptide-based IMAC, and MudPIT forefficient 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). 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,AND MASS SPECTROMETRY.	18220336 [Abstract]
"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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65 AND THR-68, AND MASSSPECTROMETRY.	18187866 [Abstract]
"ATM and ATR substrate analysis reveals extensive protein networksresponsive 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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-112, AND MASSSPECTROMETRY.	17525332 [Abstract]
"Global proteomic profiling of phosphopeptides using electron transferdissociation 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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65; THR-70; SER-94 ANDSER-101, AND MASS SPECTROMETRY.	17287340 [Abstract]
"Global, in vivo, and site-specific phosphorylation dynamics insignaling networks."; Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,Mann M.; Cell 127:635-648(2006). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-65, AND MASSSPECTROMETRY.	17081983 [Abstract]
"TOS motif-mediated raptor binding regulates 4E-BP1 multisitephosphorylation and function."; Schalm S.S., Fingar D.C., Sabatini D.M., Blenis J.; Curr. Biol. 13:797-806(2003). Cited for: INTERACTION WITH RPTOR, AND PHOSPHORYLATION AT THR-37; THR-46; SER-65AND THR-70 BY MTOR.	12747827 [Abstract]
"Quantitative phosphoproteomic analysis of T cell receptor signalingreveals 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). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-37 AND THR-46, AND MASSSPECTROMETRY.	19690332 [Abstract]
"Toward a global characterization of the phosphoproteome in prostatecancer cells: identification of phosphoproteins in the LNCaP cellline."; Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.; Electrophoresis 28:2027-2034(2007). Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-46, AND MASSSPECTROMETRY.	17487921 [Abstract]

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