UniProt functional annotation for P07766



	UniProt functional annotation for P07766

UniProt code: P07766.

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). 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 (PubMed:10384095, PubMed:26507128). {ECO:0000269|PubMed:10384095, ECO:0000269|PubMed:15294938, ECO:0000269|PubMed:15546002, ECO:0000269|PubMed:2470098, ECO:0000269|PubMed:26507128, ECO:0000269|PubMed:8490660}.

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. Interacts with CD6 (PubMed:15294938). Interacts with NCK1 (PubMed:15972658). Interacts with NUMB; this interaction is important for TCR-CD3 internalization and subsequent degradation (PubMed:26507128). {ECO:0000269|PubMed:15136729, ECO:0000269|PubMed:15294938, ECO:0000269|PubMed:15534202, ECO:0000269|PubMed:15972658, ECO:0000269|PubMed:26507128, ECO:0000269|PubMed:9698567}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:10384095, ECO:0000269|PubMed:15294938}; Single-pass type I membrane protein {ECO:0000305}.

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

Disease: Immunodeficiency 18 (IMD18) [MIM:615615]: An autosomal recessive primary immunodeficiency characterized by onset in infancy or early childhood of recurrent infections. The severity is variable, encompassing both a mild immunodeficiency and severe combined immunodeficiency (SCID), resulting in early death without bone marrow transplantation in some patients. Immunologic work-up of the IMD18 SCID patients shows a T cell-negative, B cell-positive, natural killer (NK) cell-positive phenotype, whereas T-cell development is not impaired in the mild form of IMD18. {ECO:0000269|PubMed:15546002, ECO:0000269|PubMed:8490660}. Note=The disease is caused by variants affecting the gene represented in this entry.

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). 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 (PubMed:10384095, PubMed:26507128). {ECO:0000269\|PubMed:10384095, ECO:0000269\|PubMed:15294938, ECO:0000269\|PubMed:15546002, ECO:0000269\|PubMed:2470098, ECO:0000269\|PubMed:26507128, ECO:0000269\|PubMed:8490660}.


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. Interacts with CD6 (PubMed:15294938). Interacts with NCK1 (PubMed:15972658). Interacts with NUMB; this interaction is important for TCR-CD3 internalization and subsequent degradation (PubMed:26507128). {ECO:0000269\|PubMed:15136729, ECO:0000269\|PubMed:15294938, ECO:0000269\|PubMed:15534202, ECO:0000269\|PubMed:15972658, ECO:0000269\|PubMed:26507128, ECO:0000269\|PubMed:9698567}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:10384095, ECO:0000269\|PubMed:15294938}; Single-pass type I membrane protein {ECO:0000305}.
Ptm:		Phosphorylated on Tyr residues after T-cell receptor triggering by LCK in association with CD4/CD8. {ECO:0000269\|PubMed:2470098}.
Disease:		Immunodeficiency 18 (IMD18) [MIM:615615]: An autosomal recessive primary immunodeficiency characterized by onset in infancy or early childhood of recurrent infections. The severity is variable, encompassing both a mild immunodeficiency and severe combined immunodeficiency (SCID), resulting in early death without bone marrow transplantation in some patients. Immunologic work-up of the IMD18 SCID patients shows a T cell-negative, B cell-positive, natural killer (NK) cell-positive phenotype, whereas T-cell development is not impaired in the mild form of IMD18. {ECO:0000269\|PubMed:15546002, ECO:0000269\|PubMed:8490660}. Note=The disease is caused by variants affecting the gene represented in this entry.