4EBP2_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: 4EBP2_HUMAN
• UniProt AC: Q13542
• Protein Name: Eukaryotic translation initiation factor 4E-binding protein 2 {ECO:0000303|PubMed:7935836}
• Gene Name: EIF4EBP2 {ECO:0000312|HGNC:HGNC:3289}
• Organism: Homo sapiens (Human).
• Sequence Length: 120
• Protein Description: Repressor of translation initiation involved in synaptic plasticity, learning and memory formation (By similarity). Regulates EIF4E activity by preventing its assembly into the eIF4F complex: hypophosphorylated form of EIF4EBP2 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. [PubMed: 25533957 EIF4EBP2 is enriched in brain and acts as a regulator of synapse activity and neuronal stem cell renewal via its ability to repress translation initiation (By similarity Mediates the regulation of protein translation by hormones, growth factors and other stimuli that signal through the MAP kinase and mTORC1 pathways (By similarity]
• Protein Sequence: MSSSAGSGHQPSQSRAIPTRTVAISDAAQLPHDYCTTPGGTLFSTTPGGTRIIYDRKFLLDRRNSPMAQTPPCHLPNIPGVTSPGTLIEDSKVEVNNLNNLNNHDRKHAVGDDAQFEMDI

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	Phosphorylation	------MSSSAGSGH ------CCCCCCCCC	32.76	23401153
3	Phosphorylation	-----MSSSAGSGHQ -----CCCCCCCCCC	23.94	28450419
4	Phosphorylation	----MSSSAGSGHQP ----CCCCCCCCCCC	29.37	19664995
7	Phosphorylation	-MSSSAGSGHQPSQS -CCCCCCCCCCCCCC	32.58	28450419
12	Phosphorylation	AGSGHQPSQSRAIPT CCCCCCCCCCCCCCC	33.93	28450419
14	Phosphorylation	SGHQPSQSRAIPTRT CCCCCCCCCCCCCCE	28.19	28450419
15	Methylation	GHQPSQSRAIPTRTV CCCCCCCCCCCCCEE	28.97	-
21	Phosphorylation	SRAIPTRTVAISDAA CCCCCCCEEEEEHHH	19.43	27461979
25	Phosphorylation	PTRTVAISDAAQLPH CCCEEEEEHHHHCCC	16.09	23401153
34	Phosphorylation	AAQLPHDYCTTPGGT HHHCCCCEECCCCCC	6.67	22322096
36	Phosphorylation	QLPHDYCTTPGGTLF HCCCCEECCCCCCEE	29.78	22322096
37	Phosphorylation	LPHDYCTTPGGTLFS CCCCEECCCCCCEEE	19.17	22322096
41	Phosphorylation	YCTTPGGTLFSTTPG EECCCCCCEEECCCC	30.46	22322096
44	Phosphorylation	TPGGTLFSTTPGGTR CCCCCEEECCCCCCE	34.19	22322096
45	Phosphorylation	PGGTLFSTTPGGTRI CCCCEEECCCCCCEE	29.67	22322096
46	Phosphorylation	GGTLFSTTPGGTRII CCCEEECCCCCCEEE	20.81	22322096
50	Phosphorylation	FSTTPGGTRIIYDRK EECCCCCCEEEEECC	25.30	22322096
54	Phosphorylation	PGGTRIIYDRKFLLD CCCCEEEEECCCHHH	13.81	22322096
65	Phosphorylation	FLLDRRNSPMAQTPP CHHHCCCCCCCCCCC	17.78	23401153
70	Phosphorylation	RNSPMAQTPPCHLPN CCCCCCCCCCCCCCC	21.47	29255136
82	Phosphorylation	LPNIPGVTSPGTLIE CCCCCCCCCCCCEEC	34.81	30278072
82	O-linked_Glycosylation	LPNIPGVTSPGTLIE CCCCCCCCCCCCEEC	34.81	OGP
83	Phosphorylation	PNIPGVTSPGTLIED CCCCCCCCCCCEECC	20.94	30278072
86	Phosphorylation	PGVTSPGTLIEDSKV CCCCCCCCEECCCCE	28.13	22199227
91	Phosphorylation	PGTLIEDSKVEVNNL CCCEECCCCEECCCC	26.30	22199227
99	Deamidated asparagine	KVEVNNLNNLNNHDR CEECCCCCCCCCCCC	53.73	-
99	Deamidation	KVEVNNLNNLNNHDR CEECCCCCCCCCCCC	53.73	-
102	Deamidation	VNNLNNLNNHDRKHA CCCCCCCCCCCCCCC	46.01	-
102	Deamidated asparagine	VNNLNNLNNHDRKHA CCCCCCCCCCCCCCC	46.01	-
118	Sulfoxidation	GDDAQFEMDI----- CCCCCCCCCC-----	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
37	T	Phosphorylation	Kinase	MTOR	P42345	Uniprot
46	T	Phosphorylation	Kinase	MTOR	P42345	Uniprot
65	S	Phosphorylation	Kinase	MTOR	P42345	Uniprot
70	T	Phosphorylation	Kinase	MTOR	P42345	Uniprot

Functions of PTM Sites

Modified Location	Modified Residue	Modification	Function	Reference
18	P	Phosphorylation	First phosphorylated at Thr-37 and Thr-46 by MTOR, inducing folding of region encompassing residues from Pro-18 to Arg-62 of into a four-stranded beta-domain that sequesters the helical YXXXXLPhi motif into a partly buried beta-strand, blocking accessibility to EIF4E.	25533957
37	T	Phosphorylation	First phosphorylated at Thr-37 and Thr-46 by MTOR, inducing folding of region encompassing residues from Pro-18 to Arg-62 of into a four-stranded beta-domain that sequesters the helical YXXXXLPhi motif into a partly buried beta-strand, blocking accessibility to EIF4E.	18669648
37	T	Phosphorylation	Phosphorylation at Thr-37, Thr-46, Ser-65, Thr-70 and Ser-83 is mediated by MTOR and corresponds to the hyperphosphorylated form: it abolishes binding to EIF4E by inducing folding of intrinsically disordered regions.	18669648
37	T	Phosphorylation	Protein phosphorylated at Thr-37 and Thr-46 is however unstable and subsequent phosphorylation at Ser-65, Thr-70 and Ser-83 is required to stabilize the fold, decreasing affinity for EIF4E by a factor of 4000.	18669648
46	T	Phosphorylation	First phosphorylated at Thr-37 and Thr-46 by MTOR, inducing folding of region encompassing residues from Pro-18 to Arg-62 of into a four-stranded beta-domain that sequesters the helical YXXXXLPhi motif into a partly buried beta-strand, blocking accessibility to EIF4E.	18669648
46	T	Phosphorylation	Phosphorylation at Thr-37, Thr-46, Ser-65, Thr-70 and Ser-83 is mediated by MTOR and corresponds to the hyperphosphorylated form: it abolishes binding to EIF4E by inducing folding of intrinsically disordered regions.	18669648
46	T	Phosphorylation	Protein phosphorylated at Thr-37 and Thr-46 is however unstable and subsequent phosphorylation at Ser-65, Thr-70 and Ser-83 is required to stabilize the fold, decreasing affinity for EIF4E by a factor of 4000.	18669648
62	R	Phosphorylation	First phosphorylated at Thr-37 and Thr-46 by MTOR, inducing folding of region encompassing residues from Pro-18 to Arg-62 of into a four-stranded beta-domain that sequesters the helical YXXXXLPhi motif into a partly buried beta-strand, blocking accessibility to EIF4E.	25533957
65	S	Phosphorylation	Phosphorylation at Thr-37, Thr-46, Ser-65, Thr-70 and Ser-83 is mediated by MTOR and corresponds to the hyperphosphorylated form: it abolishes binding to EIF4E by inducing folding of intrinsically disordered regions.	25533957
65	S	Phosphorylation	Protein phosphorylated at Thr-37 and Thr-46 is however unstable and subsequent phosphorylation at Ser-65, Thr-70 and Ser-83 is required to stabilize the fold, decreasing affinity for EIF4E by a factor of 4000.	25533957
70	T	Phosphorylation	Phosphorylation at Thr-37, Thr-46, Ser-65, Thr-70 and Ser-83 is mediated by MTOR and corresponds to the hyperphosphorylated form: it abolishes binding to EIF4E by inducing folding of intrinsically disordered regions.	25533957
70	T	Phosphorylation	Protein phosphorylated at Thr-37 and Thr-46 is however unstable and subsequent phosphorylation at Ser-65, Thr-70 and Ser-83 is required to stabilize the fold, decreasing affinity for EIF4E by a factor of 4000.	25533957
83	S	Phosphorylation	Phosphorylation at Thr-37, Thr-46, Ser-65, Thr-70 and Ser-83 is mediated by MTOR and corresponds to the hyperphosphorylated form: it abolishes binding to EIF4E by inducing folding of intrinsically disordered regions.	25533957
83	S	Phosphorylation	Protein phosphorylated at Thr-37 and Thr-46 is however unstable and subsequent phosphorylation at Ser-65, Thr-70 and Ser-83 is required to stabilize the fold, decreasing affinity for EIF4E by a factor of 4000.	25533957
99	N	Amidation	Deamidated at Asn-99 and Asn-102 to aspartate (Asp) in brain.	-
102	N	Amidation	Deamidated at Asn-99 and Asn-102 to aspartate (Asp) in brain.	-

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of 4EBP2_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
IF4E_HUMAN	EIF4E	physical	26344197
TBCA_HUMAN	TBCA	physical	26344197

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.

Related Literatures of Post-Translational Modification

Phosphorylation

"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-37; THR-41; SER-44 ANDTHR-45, AND MASS SPECTROMETRY.
PubMed: 19413330

"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 MASSSPECTROMETRY.
PubMed: 19690332

"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 AND THR-46, AND MASSSPECTROMETRY.
PubMed: 18669648