UniProt functional annotation for P20963



	UniProt functional annotation for P20963

UniProt code: P20963.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: 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, PubMed:7509083). CD3Z ITAMs phosphorylation creates multiple docking sites for the protein kinase ZAP70 leading to ZAP70 phosphorylation and its conversion into a catalytically active enzyme (PubMed:7509083). Plays an important role in intrathymic T-cell differentiation. Additionally, participates in the activity-dependent synapse formation of retinal ganglion cells (RGCs) in both the retina and dorsal lateral geniculate nucleus (dLGN) (By similarity). {ECO:0000250|UniProtKB:P24161, ECO:0000269|PubMed:16027224, ECO:0000269|PubMed:2470098, ECO:0000269|PubMed:28465009, ECO:0000269|PubMed:7509083}.

Subunit: The TCR-CD3 complex is composed of a CD3D/CD3E and a CD3G/CD3E heterodimers that preferentially associate with TCRalpha and TCRbeta, respectively, to form TCRalpha/CD3E/CD3G and TCRbeta/CD3G/CD3E trimers. In turn, the hexamer interacts with CD3Z homodimer to form the TCR-CD3 complex. Alternatively, TCRalpha and TCRbeta can be replaced by TCRgamma and TCRdelta (PubMed:17055436). Interacts with SLA (PubMed:10449770). Interacts with TRAT1 (PubMed:11390434). Interacts with DOCK2 (PubMed:12176041). Interacts with SLA2. Interacts with SHB (PubMed:9484780). Interacts with ZAP70 (PubMed:26783323, PubMed:7659156). Interacts (tyrosine phosphorylated) with SHC1 (via SH2 domain) (PubMed:7544002). Interacts with PTPRC (PubMed:15684325). Interacts with CRK; this interaction regulates CD3Z phosphorylation (PubMed:28465009). Interacts (on T cell side) with CD81, ICAM1 and CD9 at immunological synapses between antigen-presenting cells and T cells (PubMed:23858057). Interacts with CD160 (PubMed:11978774). Interacts with LY6E (By similarity). {ECO:0000250|UniProtKB:P24161, ECO:0000269|PubMed:10449770, ECO:0000269|PubMed:11390434, ECO:0000269|PubMed:11978774, ECO:0000269|PubMed:12176041, ECO:0000269|PubMed:15684325, ECO:0000269|PubMed:17055436, ECO:0000269|PubMed:23858057, ECO:0000269|PubMed:26783323, ECO:0000269|PubMed:28465009, ECO:0000269|PubMed:7544002, ECO:0000269|PubMed:7659156, ECO:0000269|PubMed:9484780}.

Subunit: (Microbial infection) Interacts with HIV-1 Nef; this interaction up-regulates the expression of the Fas ligand (FASLG) at the cell surface. {ECO:0000269|PubMed:10224289}.

Subunit: (Microbial infection) Interacts with HIV-2 Nef protein; this interaction induces down-regulation of cell surface TCR/CD3 complexes. {ECO:0000269|PubMed:16051847, ECO:0000269|PubMed:9811718}.

Subcellular location: Cell membrane {ECO:0000250|UniProtKB:P24161}; Single-pass type I membrane protein.

Tissue specificity: CD3Z is expressed in normal lymphoid tissue and in peripheral blood mononuclear cells (PBMCs) (PubMed:11722641). {ECO:0000269|PubMed:11722641}.

Domain: The ITAM domains mediate interaction with SHB.

Ptm: Phosphorylated on Tyr residues after T-cell receptor triggering by LCK in association with CD4/CD8. {ECO:0000269|PubMed:2470098}.

Disease: Immunodeficiency 25 (IMD25) [MIM:610163]: An immunological deficiency characterized by T-cells impaired immune response to alloantigens, tetanus toxoid and mitogens. {ECO:0000269|PubMed:16672702}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the CD3Z/FCER1G family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		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, PubMed:7509083). CD3Z ITAMs phosphorylation creates multiple docking sites for the protein kinase ZAP70 leading to ZAP70 phosphorylation and its conversion into a catalytically active enzyme (PubMed:7509083). Plays an important role in intrathymic T-cell differentiation. Additionally, participates in the activity-dependent synapse formation of retinal ganglion cells (RGCs) in both the retina and dorsal lateral geniculate nucleus (dLGN) (By similarity). {ECO:0000250\|UniProtKB:P24161, ECO:0000269\|PubMed:16027224, ECO:0000269\|PubMed:2470098, ECO:0000269\|PubMed:28465009, ECO:0000269\|PubMed:7509083}.


Subunit:		The TCR-CD3 complex is composed of a CD3D/CD3E and a CD3G/CD3E heterodimers that preferentially associate with TCRalpha and TCRbeta, respectively, to form TCRalpha/CD3E/CD3G and TCRbeta/CD3G/CD3E trimers. In turn, the hexamer interacts with CD3Z homodimer to form the TCR-CD3 complex. Alternatively, TCRalpha and TCRbeta can be replaced by TCRgamma and TCRdelta (PubMed:17055436). Interacts with SLA (PubMed:10449770). Interacts with TRAT1 (PubMed:11390434). Interacts with DOCK2 (PubMed:12176041). Interacts with SLA2. Interacts with SHB (PubMed:9484780). Interacts with ZAP70 (PubMed:26783323, PubMed:7659156). Interacts (tyrosine phosphorylated) with SHC1 (via SH2 domain) (PubMed:7544002). Interacts with PTPRC (PubMed:15684325). Interacts with CRK; this interaction regulates CD3Z phosphorylation (PubMed:28465009). Interacts (on T cell side) with CD81, ICAM1 and CD9 at immunological synapses between antigen-presenting cells and T cells (PubMed:23858057). Interacts with CD160 (PubMed:11978774). Interacts with LY6E (By similarity). {ECO:0000250\|UniProtKB:P24161, ECO:0000269\|PubMed:10449770, ECO:0000269\|PubMed:11390434, ECO:0000269\|PubMed:11978774, ECO:0000269\|PubMed:12176041, ECO:0000269\|PubMed:15684325, ECO:0000269\|PubMed:17055436, ECO:0000269\|PubMed:23858057, ECO:0000269\|PubMed:26783323, ECO:0000269\|PubMed:28465009, ECO:0000269\|PubMed:7544002, ECO:0000269\|PubMed:7659156, ECO:0000269\|PubMed:9484780}.
Subunit:		(Microbial infection) Interacts with HIV-1 Nef; this interaction up-regulates the expression of the Fas ligand (FASLG) at the cell surface. {ECO:0000269\|PubMed:10224289}.
Subunit:		(Microbial infection) Interacts with HIV-2 Nef protein; this interaction induces down-regulation of cell surface TCR/CD3 complexes. {ECO:0000269\|PubMed:16051847, ECO:0000269\|PubMed:9811718}.
Subcellular location:		Cell membrane {ECO:0000250\|UniProtKB:P24161}; Single-pass type I membrane protein.
Tissue specificity:		CD3Z is expressed in normal lymphoid tissue and in peripheral blood mononuclear cells (PBMCs) (PubMed:11722641). {ECO:0000269\|PubMed:11722641}.
Domain:		The ITAM domains mediate interaction with SHB.
Ptm:		Phosphorylated on Tyr residues after T-cell receptor triggering by LCK in association with CD4/CD8. {ECO:0000269\|PubMed:2470098}.
Disease:		Immunodeficiency 25 (IMD25) [MIM:610163]: An immunological deficiency characterized by T-cells impaired immune response to alloantigens, tetanus toxoid and mitogens. {ECO:0000269\|PubMed:16672702}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the CD3Z/FCER1G family. {ECO:0000305}.