CD3D_HUMAN - PTM Information in dbPTM

Basic Information of Protein

• UniProt ID: CD3D_HUMAN
• UniProt AC: P04234
• Protein Name: T-cell surface glycoprotein CD3 delta chain
• Gene Name: CD3D
• Organism: Homo sapiens (Human).
• Sequence Length: 171
• 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]
• Protein Sequence: MEHSTFLSGLVLATLLSQVSPFKIPIEELEDRVFVNCNTSITWVEGTVGTLLSDITRLDLGKRILDPRGIYRCNGTDIYKDKESTVQVHYRMCQSCVELDPATVAGIIVTDVIATLLLALGVFCFAGHETGRLSGAADTQALLRNDQVYQPLRDRDDAQYSHLGGNWARNK

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
20	Phosphorylation	ATLLSQVSPFKIPIE HHHHHCCCCCCCCHH	19.58	24719451
38	N-linked_Glycosylation	DRVFVNCNTSITWVE CCEEEECCCCEEEEE	31.49	UniProtKB CARBOHYD
47	O-linked_Glycosylation	SITWVEGTVGTLLSD CEEEEECHHHHHHHH	11.40	OGP
50	O-linked_Glycosylation	WVEGTVGTLLSDITR EEECHHHHHHHHHHH	21.86	OGP
62	Ubiquitination	ITRLDLGKRILDPRG HHHHCCCCCCCCCCC	43.49	-
74	N-linked_Glycosylation	PRGIYRCNGTDIYKD CCCCEEECCCCCCCC	47.61	UniProtKB CARBOHYD
80	Ubiquitination	CNGTDIYKDKESTVQ ECCCCCCCCCCCCCH	63.76	-
82	Ubiquitination	GTDIYKDKESTVQVH CCCCCCCCCCCCHHE	49.79	-
139	Phosphorylation	RLSGAADTQALLRND CCCCCCHHHHHHHCC	15.83	-
149	Phosphorylation	LLRNDQVYQPLRDRD HHHCCCCCCCCCCCC	9.97	19605366
160	Phosphorylation	RDRDDAQYSHLGGNW CCCCCHHHCCCCCCC	10.36	19605366
161	Phosphorylation	DRDDAQYSHLGGNWA CCCCHHHCCCCCCCC	10.52	28796482

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
-	K	Ubiquitination	E3 ubiquitin ligase	AMFR	Q9UKV5	PMID:11724934
-	K	Ubiquitination	E3 ubiquitin ligase	TRIM13	O60858	PMID:17314412
-	K	Ubiquitination	E3 ubiquitin ligase	SYVN1	Q86TM6	PMID:21199683

Functions of PTM Sites

Oops, there are no descriptions of PTM sites of CD3D_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 CD3D_HUMAN !!

Protein-Protein Interaction

Interacting Protein	Gene Name	Interaction Type	PPI Reference
CD8A_HUMAN	CD8A	physical	12215456
CALX_HUMAN	CANX	physical	8621641
DERL1_HUMAN	DERL1	physical	17872946
AMFR_HUMAN	AMFR	physical	17872946
TERA_HUMAN	VCP	physical	17872946
TERA_HUMAN	VCP	physical	15331598
PDIA2_HUMAN	PDIA2	physical	19942855
CALX_HUMAN	CANX	physical	25241761

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
• 608971: Severe combined immunodeficiency autosomal recessive T-cell-negative/B-cell-positive/NK-cell-positive (T(-)B(+)NK(+) SCID)
• 615617: Immunodeficiency 19 (IMD19)
• 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

"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-149 AND TYR-160, ANDMASS SPECTROMETRY.
PubMed: 19690332

"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-149 AND TYR-160, 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-149 AND TYR-160, 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-149 AND TYR-160, ANDMASS SPECTROMETRY.
PubMed: 12522270