Details of the Drug Therapeutic Target (DTT)

General Information of Drug Therapeutic Target (DTT) (ID: TTZAT79)

• DTT Name: T-cell surface glycoprotein CD3 epsilon (CD3E)
• Synonyms: T3E; T-cell surface glycoprotein CD3 epsilon chain; T-cell surface antigen T3/Leu-4 epsilon chain; CD3e
• Gene Name: CD3E
• DTT Type: Successful target; [1]
• UniProt ID: CD3E_HUMAN
• TTD ID: T87075
• Sequence:
  MQSGTHWRVLGLCLLSVGVWGQDGNEEMGGITQTPYKVSISGTTVILTCPQYPGSEILWQ
  HNDKNIGGDEDDKNIGSDEDHLSLKEFSELEQSGYYVCYPRGSKPEDANFYLYLRARVCE
  NCMEMDVMSVATIVIVDICITGGLLLLVYYWSKNRKAKAKPVTRGAGAGGRQRGQNKERP
  PPVPNPDYEPIRKGQRDLYSGLNQRRI
• Function: 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. In addition of this role of signal transduction in T-cell activation, CD3E plays an essential role in correct T-cell development. 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. Part of the TCR-CD3 complex present on T-lymphocyte cell surface that plays an essential role in adaptive immune response.
• KEGG Pathway:
  Hematopoietic cell lineage (hsa04640)
  T cell receptor signaling pathway (hsa04660)
  Chagas disease (American trypanosomiasis) (hsa05142)
  Measles (hsa05162)
  HTLV-I infection (hsa05166)
  Primary immunodeficiency (hsa05340)
• Reactome Pathway:
  Phosphorylation of CD3 and TCR zeta chains (R-HSA-202427)
  Translocation of ZAP-70 to Immunological synapse (R-HSA-202430)
  Generation of second messenger molecules (R-HSA-202433)
  PD-1 signaling (R-HSA-389948)
  Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell (R-HSA-198933)

Molecular Interaction Atlas (MIA) of This DTT

1 Approved Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Muromonab	DM8ANCF	Organ transplant rejection	NE84	Approved	[1]

4 Clinical Trial Drug(s) Targeting This DTT

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Ertumaxomab	DM5Z3VP	Breast cancer	2C60-2C65	Phase 2	[2]
Resimmune	DMT5QSD	Cutaneous T-cell lymphoma	2B01	Phase 2	[3]
Autologous T-cell therapy	DMOAET3	Prostate cancer	2C82.0	Phase 1	[4]
MT-110	DMPCUN5	Solid tumour/cancer	2A00-2F9Z	Phase 1	[5]

Molecular Expression Atlas (MEA) of This DTT

Disease Name	ICD 11	Studied Tissue	p-value	Fold-Change	Z-score
Prostate cancer	2C82	Prostate	1.53E-06	-0.93	-1.37
Breast cancer	2C82	Breast tissue	1.62E-01	0.11	0.14
Melanoma	2C82	Skin	1.70E-04	1.29	1.26

References

• [1] Basiliximab: a review of its use as induction therapy in renal transplantation. Drugs. 2003;63(24):2803-35.
• [2] Trifunctional antibody ertumaxomab: Non-immunological effects on Her2 receptor activity and downstream signaling. MAbs. 2012 Sep-Oct;4(5):614-22.
• [3] Resimmune, an anti-CD3 recombinant immunotoxin, induces durable remissions in patients with cutaneous T-cell lymphoma.Haematologica.2015 Jun;100(6):794-800.
• [4] Antitumor activities of PSMA CD3 diabodies by redirected T-cell lysis of prostate cancer cells. Immunotherapy. 2013 Jan;5(1):27-38.
• [5] EpCAM/CD3-Bispecific T-cell engaging antibody MT110 eliminates primary human pancreatic cancer stem cells. Clin Cancer Res. 2012 Jan 15;18(2):465-74.