CD3E_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: CD3E_HUMAN
• UniProt AC: P07766
• Protein Name: T-cell surface glycoprotein CD3 epsilon chain
• Gene Name: CD3E
• Organism: Homo sapiens (Human).
• Sequence Length: 207
• Subcellular Localization: Cell membrane ; Single-pass type I membrane protein .
• Protein Description: Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response. When antigen presenting cells (APCs) activate T-cell receptor (TCR), TCR-mediated signals are transmitted across the cell membrane by the CD3 chains CD3D, CD3E, CD3G and CD3Z. All CD3 chains contain immunoreceptor tyrosine-based activation motifs (ITAMs) in their cytoplasmic domain. Upon TCR engagement, these motifs become phosphorylated by Src family protein tyrosine kinases LCK and FYN, resulting in the activation of downstream signaling pathways. [PubMed: 2470098 In addition of this role of signal transduction in T-cell activation, CD3E plays an essential role in correct T-cell developement. Initiates the TCR-CD3 complex assembly by forming the two heterodimers CD3D/CD3E and CD3G/CD3E. Participates also in internalization and cell surface down-regulation of TCR-CD3 complexes via endocytosis sequences present in CD3E cytosolic region]
• Protein Sequence: MQSGTHWRVLGLCLLSVGVWGQDGNEEMGGITQTPYKVSISGTTVILTCPQYPGSEILWQHNDKNIGGDEDDKNIGSDEDHLSLKEFSELEQSGYYVCYPRGSKPEDANFYLYLRARVCENCMEMDVMSVATIVIVDICITGGLLLLVYYWSKNRKAKAKPVTRGAGAGGRQRGQNKERPPPVPNPDYEPIRKGQRDLYSGLNQRRI

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
3	Phosphorylation	-----MQSGTHWRVL -----CCCCHHHHHH	44.34	24043423
5	Phosphorylation	---MQSGTHWRVLGL ---CCCCHHHHHHHH	24.42	24043423
16	Phosphorylation	VLGLCLLSVGVWGQD HHHHHEEECCEECCC	12.13	22210691
32	Phosphorylation	NEEMGGITQTPYKVS CCCCCCCCCCCEEEE	29.66	24043423
34	Phosphorylation	EMGGITQTPYKVSIS CCCCCCCCCEEEEEE	21.67	24043423
36	Phosphorylation	GGITQTPYKVSISGT CCCCCCCEEEEEECC	27.66	24043423
43	O-linked_Glycosylation	YKVSISGTTVILTCP EEEEEECCEEEEECC	15.88	OGP
48	O-linked_Glycosylation	SGTTVILTCPQYPGS ECCEEEEECCCCCCC	15.83	OGP
64	Ubiquitination	ILWQHNDKNIGGDED EEEECCCCCCCCCCC	56.64	29967540
73	Ubiquitination	IGGDEDDKNIGSDED CCCCCCCCCCCCCCC	63.89	29967540
77	Phosphorylation	EDDKNIGSDEDHLSL CCCCCCCCCCCCCCH	33.75	-
83	Phosphorylation	GSDEDHLSLKEFSEL CCCCCCCCHHHHHHH	33.69	24719451
85	Ubiquitination	DEDHLSLKEFSELEQ CCCCCCHHHHHHHHH	54.03	-
104	Ubiquitination	VCYPRGSKPEDANFY EEEECCCCCCCCCEE	56.07	22505724
158	Ubiquitination	WSKNRKAKAKPVTRG HHCCCCCCCCCCCCC	61.04	24816145
177	Ubiquitination	GRQRGQNKERPPPVP CCCCCCCCCCCCCCC	47.41	24816145
188	Phosphorylation	PPVPNPDYEPIRKGQ CCCCCCCCCCCCCCC	25.51	19605366
199	Phosphorylation	RKGQRDLYSGLNQRR CCCCCCCCCCCHHCC	12.65	19605366
200	Phosphorylation	KGQRDLYSGLNQRRI CCCCCCCCCCHHCCC	44.07	30576142

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
188	Y	Phosphorylation	Kinase	FYN	P06241	PSP
199	Y	Phosphorylation	Kinase	FYN	P06241	PSP

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of CD3E_HUMAN !!

Disease-associated PTM Sites based on SAP

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

Oops, there are no SNP-PTM records of CD3E_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
NUCL_HUMAN	NCL	physical	11115514
P85A_HUMAN	PIK3R1	physical	9312149
RPA34_HUMAN	CD3EAP	physical	10373416
NCK2_HUMAN	NCK2	physical	12110186
JAK3_HUMAN	JAK3	physical	11349123
CD3G_HUMAN	CD3G	physical	9582308
TOP2B_HUMAN	TOP2B	physical	8626450
CD3Z_HUMAN	CD247	physical	14523017
LCK_HUMAN	LCK	physical	14523017
P85A_HUMAN	PIK3R1	physical	19190244
P85B_HUMAN	PIK3R2	physical	19190244
ZAP70_HUMAN	ZAP70	physical	8906806
IPIL1_HUMAN	ITPRIPL1	physical	26186194
GHDC_HUMAN	GHDC	physical	26186194
1A02_HUMAN	HLA-A	physical	26186194
1A03_HUMAN	HLA-A	physical	26186194
1A01_HUMAN	HLA-A	physical	26186194
1A26_HUMAN	HLA-A	physical	26186194
LCAP_HUMAN	LNPEP	physical	26186194
GP1BB_HUMAN	GP1BB	physical	26186194
TM2D3_HUMAN	TM2D3	physical	26186194
CJ035_HUMAN	C10orf35	physical	26186194
LCAP_HUMAN	LNPEP	physical	28514442
GHDC_HUMAN	GHDC	physical	28514442
TM2D3_HUMAN	TM2D3	physical	28514442
CJ035_HUMAN	C10orf35	physical	28514442
GP1BB_HUMAN	GP1BB	physical	28514442

Drug and Disease Associations

• Kegg Disease
• H00002: Acute lymphoblastic leukemia (ALL) (precursor T lymphoblastic leukemia)
• H00091: T-B+Severe combined immunodeficiencies (SCIDs), including the following eight diseases: X-linked SCI
• OMIM Disease
• 615615: Immunodeficiency 18 (IMD18)
• Kegg Drug
• D05092: Muromonab-CD3 (JAN/USAN/INN); Orthoclone okt3 (TN)
• D06314: Visilizumab (USAN/INN); Nuvion (TN)
• D08959: Otelixizumab (USAN)
• D09013: Teplizumab (USAN/INN)
• D09207: Catumaxomab (INN)
• D09325: Blinatumomab (USAN/INN)
• DrugBank
• There are no disease associations of PTM sites.

Related Literatures of Post-Translational Modification

Phosphorylation

"Structural basis for Syk tyrosine kinase ubiquity in signaltransduction pathways revealed by the crystal structure of itsregulatory SH2 domains bound to a dually phosphorylated ITAMpeptide.";
Fuetterer K., Wong J., Grucza R.A., Chan A.C., Waksman G.;
J. Mol. Biol. 281:523-537(1998).
Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 186-203 IN COMPLEX WITH SYK,AND PHOSPHORYLATION AT TYR-188 AND TYR-199.
PubMed: 9698567

"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 TYR-188 AND TYR-199, ANDMASS SPECTROMETRY.
PubMed: 19690332

"Global survey of phosphotyrosine signaling identifies oncogenickinases in lung cancer.";
Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J.,Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L.,Mitchell J., Wetzel R., Macneill J., Ren J.M., Yuan J.,Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X.,Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J.;
Cell 131:1190-1203(2007).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-199, AND MASSSPECTROMETRY.
PubMed: 18083107

"Quantitative phosphoproteome analysis using a dendrimer conjugationchemistry and tandem mass spectrometry.";
Tao W.A., Wollscheid B., O'Brien R., Eng J.K., Li X.-J.,Bodenmiller B., Watts J.D., Hood L., Aebersold R.;
Nat. Methods 2:591-598(2005).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-188 AND TYR-199, ANDMASS SPECTROMETRY.
PubMed: 16094384

"Immunoaffinity profiling of tyrosine phosphorylation in cancercells.";
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H.,Zha X.-M., Polakiewicz R.D., Comb M.J.;
Nat. Biotechnol. 23:94-101(2005).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-188 AND TYR-199, ANDMASS SPECTROMETRY.
PubMed: 15592455

"Profiling of tyrosine phosphorylation pathways in human cells usingmass spectrometry.";
Salomon A.R., Ficarro S.B., Brill L.M., Brinker A., Phung Q.T.,Ericson C., Sauer K., Brock A., Horn D.M., Schultz P.G., Peters E.C.;
Proc. Natl. Acad. Sci. U.S.A. 100:443-448(2003).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-199, AND MASSSPECTROMETRY.
PubMed: 12522270