4EBP1_RAT - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: 4EBP1_RAT
• UniProt AC: Q62622
• Protein Name: Eukaryotic translation initiation factor 4E-binding protein 1
• Gene Name: Eif4ebp1
• Organism: Rattus norvegicus (Rat).
• Sequence Length: 117
• 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 (By similarity). Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways. [PubMed: 7939721]
• Protein Sequence: MSAGSSCSQTPSRAIPTRRVALGDGVQLPPGDYSTTPGGTLFSTTPGGTRIIYDRKFLMECRNSPVAKTPPKDLPTIPGVTSPTSDEPPMQASQSHLHSSPEDKRAGGEESQFEMDI

Overview of Protein Modification Sites with Functional and Structural Information

Experimental Post-Translational Modification Sites

* ASA = Accessible Surface Area

Locations	Modification	Substrate Peptides & Secondary Structure	ASA (%)	Reference
2	Acetylation	------MSAGSSCSQ ------CCCCCCCCC	41.14	-
2	Phosphorylation	------MSAGSSCSQ ------CCCCCCCCC	41.14	27097102
5	Phosphorylation	---MSAGSSCSQTPS ---CCCCCCCCCCCC	28.08	23984901
10	Phosphorylation	AGSSCSQTPSRAIPT CCCCCCCCCCCCCCC	13.62	23984901
12	Phosphorylation	SSCSQTPSRAIPTRR CCCCCCCCCCCCCCC	37.42	23984901
17	Phosphorylation	TPSRAIPTRRVALGD CCCCCCCCCCEEECC	25.62	23984901
33	Phosphorylation	VQLPPGDYSTTPGGT CCCCCCCCCCCCCCC	17.52	27097102
34	Phosphorylation	QLPPGDYSTTPGGTL CCCCCCCCCCCCCCE	30.46	27097102
35	Phosphorylation	LPPGDYSTTPGGTLF CCCCCCCCCCCCCEE	30.68	27097102
36	Phosphorylation	PPGDYSTTPGGTLFS CCCCCCCCCCCCEEE	17.62	12944322
40	Phosphorylation	YSTTPGGTLFSTTPG CCCCCCCCEEECCCC	30.46	27097102
43	Phosphorylation	TPGGTLFSTTPGGTR CCCCCEEECCCCCEE	34.19	27097102
44	Phosphorylation	PGGTLFSTTPGGTRI CCCCEEECCCCCEEE	29.67	23298284
45	Phosphorylation	GGTLFSTTPGGTRII CCCEEECCCCCEEEE	20.81	12944322
49	Phosphorylation	FSTTPGGTRIIYDRK EECCCCCEEEEEECH	25.30	27097102
53	Phosphorylation	PGGTRIIYDRKFLME CCCEEEEEECHHHHH	13.81	23984901
64	Phosphorylation	FLMECRNSPVAKTPP HHHHHCCCCCCCCCC	11.03	7939721
69	Phosphorylation	RNSPVAKTPPKDLPT CCCCCCCCCCCCCCC	34.78	12944322
76	Phosphorylation	TPPKDLPTIPGVTSP CCCCCCCCCCCCCCC	47.29	27097102
81	Phosphorylation	LPTIPGVTSPTSDEP CCCCCCCCCCCCCCC	34.60	27097102
82	Phosphorylation	PTIPGVTSPTSDEPP CCCCCCCCCCCCCCC	24.63	27097102
84	Phosphorylation	IPGVTSPTSDEPPMQ CCCCCCCCCCCCCCC	48.88	27097102
85	Phosphorylation	PGVTSPTSDEPPMQA CCCCCCCCCCCCCCH	43.28	27097102
93	Phosphorylation	DEPPMQASQSHLHSS CCCCCCHHHHHHCCC	18.48	27097102
95	Phosphorylation	PPMQASQSHLHSSPE CCCCHHHHHHCCCHH	26.06	27097102
99	Phosphorylation	ASQSHLHSSPEDKRA HHHHHHCCCHHHHHC	54.68	27097102
100	Phosphorylation	SQSHLHSSPEDKRAG HHHHHCCCHHHHHCC	22.89	27097102
111	Phosphorylation	KRAGGEESQFEMDI- HHCCCCCCCCCCCC-	35.55	11146653

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
36	T	Phosphorylation	Kinase	MAPK-FAMILY	-	GPS
36	T	Phosphorylation	Kinase	MTOR	P42346	PSP
36	T	Phosphorylation	Kinase	MAPK1	P28482	GPS
45	T	Phosphorylation	Kinase	MAPK-FAMILY	-	GPS
45	T	Phosphorylation	Kinase	MAPK1	P28482	GPS
45	T	Phosphorylation	Kinase	MTOR	P42346	Uniprot
64	S	Phosphorylation	Kinase	CSNK2A1	P68400	GPS
64	S	Phosphorylation	Kinase	DYRK2	-	Uniprot
64	S	Phosphorylation	Kinase	MAPK-FAMILY	-	GPS
64	S	Phosphorylation	Kinase	MTOR	P42346	Uniprot
64	S	Phosphorylation	Kinase	MAPK3	P21708	Uniprot
64	S	Phosphorylation	Kinase	MAPK1	P63086	Uniprot
64	S	Phosphorylation	Kinase	MAPK1	P28482	GPS
64	S	Phosphorylation	Kinase	PRKCA	P17252	GPS
69	T	Phosphorylation	Kinase	MAPK1	P28482	GPS
69	T	Phosphorylation	Kinase	MTOR	P42346	Uniprot
69	T	Phosphorylation	Kinase	MAPK-FAMILY	-	GPS
82	S	Phosphorylation	Kinase	MAPK1	P28482	GPS
82	S	Phosphorylation	Kinase	MTOR	P42346	PSP
82	S	Phosphorylation	Kinase	MAPK-FAMILY	-	GPS
99	S	Phosphorylation	Kinase	CK2-FAMILY	-	GPS
99	S	Phosphorylation	Kinase	CSNK2A1	P33674	GPS
100	S	Phosphorylation	Kinase	DYRK2	-	Uniprot
111	S	Phosphorylation	Kinase	CK2-FAMILY	-	GPS
111	S	Phosphorylation	Kinase	CSNK2A1	P33674	GPS
111	S	Phosphorylation	Kinase	ATM	Q13315	PSP

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
36	T	Phosphorylation	Not ubiquitinated when hyperphosphorylated (at Thr-36, Thr-45, Ser-64 and Thr-69) or associated with eIF4E.	22673903
36	T	Phosphorylation	Phosphorylation at Thr-36, Thr-45, Ser-64 and Thr-69, corresponding to the hyperphosphorylated form, is regulated by mTORC1 and abolishes binding to EIF4E.	22673903
36	T	ubiquitylation	Not ubiquitinated when hyperphosphorylated (at Thr-36, Thr-45, Ser-64 and Thr-69) or associated with eIF4E.	22673903
45	T	Phosphorylation	Not ubiquitinated when hyperphosphorylated (at Thr-36, Thr-45, Ser-64 and Thr-69) or associated with eIF4E.	-
45	T	Phosphorylation	Phosphorylation at Thr-36, Thr-45, Ser-64 and Thr-69, corresponding to the hyperphosphorylated form, is regulated by mTORC1 and abolishes binding to EIF4E.	8170978
45	T	ubiquitylation	Not ubiquitinated when hyperphosphorylated (at Thr-36, Thr-45, Ser-64 and Thr-69) or associated with eIF4E.	-
64	S	Phosphorylation	Not ubiquitinated when hyperphosphorylated (at Thr-36, Thr-45, Ser-64 and Thr-69) or associated with eIF4E.	7939721
64	S	Phosphorylation	Phosphorylation at Thr-36, Thr-45, Ser-64 and Thr-69, corresponding to the hyperphosphorylated form, is regulated by mTORC1 and abolishes binding to EIF4E.	7939721
64	S	ubiquitylation	Not ubiquitinated when hyperphosphorylated (at Thr-36, Thr-45, Ser-64 and Thr-69) or associated with eIF4E.	7939721
69	T	Phosphorylation	Not ubiquitinated when hyperphosphorylated (at Thr-36, Thr-45, Ser-64 and Thr-69) or associated with eIF4E.	-
69	T	Phosphorylation	Phosphorylation at Thr-36, Thr-45, Ser-64 and Thr-69, corresponding to the hyperphosphorylated form, is regulated by mTORC1 and abolishes binding to EIF4E.	8170978
69	T	ubiquitylation	Not ubiquitinated when hyperphosphorylated (at Thr-36, Thr-45, Ser-64 and Thr-69) or associated with eIF4E.	-

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of 4EBP1_RAT !!

Protein-Protein Interaction

Oops, there are no PPI records of 4EBP1_RAT !!

Drug and Disease Associations

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

Related Literatures of Post-Translational Modification

Acetylation

"Molecular cloning and tissue distribution of PHAS-I, an intracellulartarget for insulin and growth factors.";
Hu C., Pang S., Kong X., Velleca M., Lawrence J.C. Jr.;
Proc. Natl. Acad. Sci. U.S.A. 91:3730-3734(1994).
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 18-33; 43-53; 62-80AND 98-117, PHOSPHORYLATION, AND TISSUE SPECIFICITY.
PubMed: 8170978

Phosphorylation

"PHAS-I as a link between mitogen-activated protein kinase andtranslation initiation.";
Lin T.-A., Kong X., Haystead T.A.J., Pause A., Belsham G.J.,Sonenberg N., Lawrence J.C. Jr.;
Science 266:653-656(1994).
Cited for: FUNCTION, INTERACTION WITH EIF4E, PHOSPHORYLATION AT SER-64 BY MAPK1AND MAPK3, AND MUTAGENESIS OF SER-64.
PubMed: 7939721