CD3Z_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: CD3Z_HUMAN
• UniProt AC: P20963
• Protein Name: T-cell surface glycoprotein CD3 zeta chain
• Gene Name: CD247
• Organism: Homo sapiens (Human).
• Sequence Length: 164
• Subcellular Localization: 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]
• Protein Sequence: MKWKALFTAAILQAQLPITEAQSFGLLDPKLCYLLDGILFIYGVILTALFLRVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPQRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR

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
54	Ubiquitination	TALFLRVKFSRSADA HHHHHHHHCCCCCCC	31.05	-
58	Phosphorylation	LRVKFSRSADAPAYQ HHHHCCCCCCCCHHH	29.33	14729942
64	Phosphorylation	RSADAPAYQQGQNQL CCCCCCHHHHHHHHH	10.58	19605366
72	Phosphorylation	QQGQNQLYNELNLGR HHHHHHHHHHHCCCC	9.23	19605366
83	Phosphorylation	NLGRREEYDVLDKRR CCCCHHHHHHHHHCC	13.44	19605366
88	Ubiquitination	EEYDVLDKRRGRDPE HHHHHHHHCCCCCHH	39.57	24816145
96	Ubiquitination	RRGRDPEMGGKPQRR CCCCCHHHCCCCCCC	11.89	24816145
99 (in isoform 3)	Ubiquitination	-	32.04	-
99	Ubiquitination	RDPEMGGKPQRRKNP CCHHHCCCCCCCCCC	32.04	29967540
103	Ubiquitination	MGGKPQRRKNPQEGL HCCCCCCCCCCCCCH	37.54	22505724
104	Ubiquitination	GGKPQRRKNPQEGLY CCCCCCCCCCCCCHH	75.15	22505724
110 (in isoform 3)	Phosphorylation	-	4.00	24719451
111	Phosphorylation	KNPQEGLYNELQKDK CCCCCCHHHHHHHHH	19.90	19605366
111	Ubiquitination	KNPQEGLYNELQKDK CCCCCCHHHHHHHHH	19.90	22505724
112	Ubiquitination	NPQEGLYNELQKDKM CCCCCHHHHHHHHHH	48.85	22505724
115	Ubiquitination	EGLYNELQKDKMAEA CCHHHHHHHHHHHHH	45.80	29967540
116	Ubiquitination	GLYNELQKDKMAEAY CHHHHHHHHHHHHHH	72.45	-
117	Ubiquitination	LYNELQKDKMAEAYS HHHHHHHHHHHHHHH	32.76	29967540
118	Ubiquitination	YNELQKDKMAEAYSE HHHHHHHHHHHHHHH	47.23	29967540
119	Ubiquitination	NELQKDKMAEAYSEI HHHHHHHHHHHHHHH	6.13	24816145
123	Phosphorylation	KDKMAEAYSEIGMKG HHHHHHHHHHHCCCC	9.80	19605366
124	Phosphorylation	DKMAEAYSEIGMKGE HHHHHHHHHHCCCCC	29.77	28796482
128	Ubiquitination	EAYSEIGMKGERRRG HHHHHHCCCCCCCCC	6.56	22505724
129	Ubiquitination	AYSEIGMKGERRRGK HHHHHCCCCCCCCCC	53.02	22505724
129	Acetylation	AYSEIGMKGERRRGK HHHHHCCCCCCCCCC	53.02	25953088
134	Ubiquitination	GMKGERRRGKGHDGL CCCCCCCCCCCCCCH	58.35	22505724
135	Ubiquitination	MKGERRRGKGHDGLY CCCCCCCCCCCCCHH	38.19	22505724
136	Ubiquitination	KGERRRGKGHDGLYQ CCCCCCCCCCCCHHH	51.79	22505724
137	Ubiquitination	GERRRGKGHDGLYQG CCCCCCCCCCCHHHC	27.26	22505724
142	Phosphorylation	GKGHDGLYQGLSTAT CCCCCCHHHCCCCCC	13.18	19605366
143	Ubiquitination	KGHDGLYQGLSTATK CCCCCHHHCCCCCCC	51.93	22505724
144	Ubiquitination	GHDGLYQGLSTATKD CCCCHHHCCCCCCCH	14.19	22505724
146	Phosphorylation	DGLYQGLSTATKDTY CCHHHCCCCCCCHHH	23.87	29978859
147	Phosphorylation	GLYQGLSTATKDTYD CHHHCCCCCCCHHHH	43.31	23403867
149	Ubiquitination	YQGLSTATKDTYDAL HHCCCCCCCHHHHHH	29.55	29967540
149	Phosphorylation	YQGLSTATKDTYDAL HHCCCCCCCHHHHHH	29.55	23403867
150	Ubiquitination	QGLSTATKDTYDALH HCCCCCCCHHHHHHH	45.68	29967540
152	Phosphorylation	LSTATKDTYDALHMQ CCCCCCHHHHHHHHH	25.51	30576142
153	Phosphorylation	STATKDTYDALHMQA CCCCCHHHHHHHHHC	14.89	19605366
159	Ubiquitination	TYDALHMQALPPR-- HHHHHHHHCCCCC--	29.06	22505724
160	Ubiquitination	YDALHMQALPPR--- HHHHHHHCCCCC---	17.92	22505724
166	Ubiquitination	QALPPR--------- HCCCCC---------		22505724
167	Ubiquitination	ALPPR---------- CCCCC----------		22505724

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
111	Y	Phosphorylation	Kinase	FYN	P06241	PhosphoELM
123	Y	Phosphorylation	Kinase	FYN	P06241	PhosphoELM
142	Y	Phosphorylation	Kinase	LCK	P06239	PSP
-	K	Ubiquitination	E3 ubiquitin ligase	ITCH	Q96J02	PMID:20637659
-	K	Ubiquitination	E3 ubiquitin ligase	CBLB	Q13191	PMID:20637659

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of CD3Z_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 CD3Z_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
TRAT1_HUMAN	TRAT1	physical	11390434
DOCK2_HUMAN	DOCK2	physical	12176041
JAK3_HUMAN	JAK3	physical	11349123
ZAP70_HUMAN	ZAP70	physical	7737297
NEF_HV1H2	nef	physical	20179761
ZAP70_HUMAN	ZAP70	physical	11353765
CBL_HUMAN	CBL	physical	11353765
CD3E_HUMAN	CD3E	physical	14523017
LCK_HUMAN	LCK	physical	14523017
ZAP70_HUMAN	ZAP70	physical	20637659
ZAP70_HUMAN	ZAP70	physical	8906806
VTNC_HUMAN	VTN	physical	21988832
PCGF2_HUMAN	PCGF2	physical	21988832
ZN281_HUMAN	ZNF281	physical	21988832
CD3E_HUMAN	CD3E	physical	25241761
DOCK2_HUMAN	DOCK2	physical	25241761
LCK_HUMAN	LCK	physical	26390156
ZAP70_HUMAN	ZAP70	physical	26390156
RNF41_HUMAN	RNF41	physical	26390156

Drug and Disease Associations

• Kegg Disease
• H00091: T-B+Severe combined immunodeficiencies (SCIDs), including the following eight diseases: X-linked SCI
• OMIM Disease
• 610163: Immunodeficiency 25 (IMD25)
• 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

"Robust phosphoproteomic profiling of tyrosine phosphorylation sitesfrom human T cells using immobilized metal affinity chromatography andtandem mass spectrometry.";
Brill L.M., Salomon A.R., Ficarro S.B., Mukherji M., Stettler-Gill M.,Peters E.C.;
Anal. Chem. 76:2763-2772(2004).
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-58 AND TYR-64, AND MASSSPECTROMETRY.
PubMed: 15144186

"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-64; TYR-72; TYR-83;TYR-111; TYR-123; TYR-142 AND TYR-153, AND MASS 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-111, 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-64; TYR-72; TYR-83;TYR-111; TYR-123; TYR-142 AND TYR-153, AND MASS 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-64; TYR-72; TYR-83;TYR-111 AND TYR-142, AND MASS 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-83; TYR-111; TYR-123 ANDTYR-142, AND MASS SPECTROMETRY.
PubMed: 12522270