UniProt functional annotation for Q02242



	UniProt functional annotation for Q02242

UniProt code: Q02242.

Organism: Mus musculus (Mouse).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.

Function: Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:10485649, PubMed:11698646, PubMed:11209085, PubMed:21300912). Delivers inhibitory signals upon binding to ligands, such as CD274/PDCD1L1 and CD273/PDCD1LG2 (PubMed:11015443, PubMed:11224527, PubMed:22641383, PubMed:18287011, PubMed:18641123). Following T-cell receptor (TCR) engagement, PDCD1 associates with CD3-TCR in the immunological synapse and directly inhibits T-cell activation (PubMed:22641383). Suppresses T-cell activation through the recruitment of PTPN11/SHP-2: following ligand-binding, PDCD1 is phosphorylated within the ITSM motif, leading to the recruitment of the protein tyrosine phosphatase PTPN11/SHP-2 that mediates dephosphorylation of key TCR proximal signaling molecules, such as ZAP70, PRKCQ/PKCtheta and CD247/CD3zeta (PubMed:11698646, PubMed:22641383). The PDCD1-mediated inhibitory pathway is exploited by tumors to attenuate anti-tumor immunity and facilitate tumor survival (By similarity). {ECO:0000250|UniProtKB:Q15116, ECO:0000269|PubMed:10485649, ECO:0000269|PubMed:11015443, ECO:0000269|PubMed:11209085, ECO:0000269|PubMed:11224527, ECO:0000269|PubMed:11698646, ECO:0000269|PubMed:18287011, ECO:0000269|PubMed:18641123, ECO:0000269|PubMed:21300912, ECO:0000269|PubMed:22641383}.

Subunit: Monomer (PubMed:15030777, PubMed:18287011, PubMed:18641123). Interacts with CD274/PDCD1L1 (PubMed:18287011). Interacts with CD273/PDCD1LG2 (PubMed:18641123). Interacts with FBXO38; leading to ubiquitination and degradation by the proteasome (By similarity). {ECO:0000250|UniProtKB:Q15116, ECO:0000269|PubMed:15030777, ECO:0000269|PubMed:18287011, ECO:0000269|PubMed:18641123}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:22641383, ECO:0000269|PubMed:30487606}; Single-pass type I membrane protein.

Tissue specificity: Thymus-specific. {ECO:0000269|PubMed:1396582}.

Developmental stage: Induced at programmed cell death. {ECO:0000269|PubMed:1396582}.

Ptm: Ubiquitinated at Lys-235 by the SCF(FBXO38) complex, leading to its proteasomal degradation. Ubiquitinated via 'Lys-48'-linked polyubiquitin chains. {ECO:0000250|UniProtKB:Q15116}.

Ptm: Tyrosine phosphorylated at Tyr-225 (within ITIM motif) and Tyr-248 (ITSM motif) upon ligand binding (PubMed:11698646, PubMed:22641383). Phosphorylation at Tyr-248 promotes the recruitment of the protein tyrosine phosphatase PTPN11/SHP-2 that mediates dephosphorylation of key TCR proximal signaling molecules, such as ZAP70, PRKCQ/PKCtheta and CD247/CD3zeta (PubMed:22641383). {ECO:0000269|PubMed:11698646, ECO:0000269|PubMed:22641383}.

Disruption phenotype: Mice grow and develop normally but exhibit splenomegaly, selective augmentation of IgG3 antibody response to a T- independent type II antigen, and enhanced proliferative responses of B- cells and myeloid cells by anti-IgM and granulocyte colony-stimulating factor stimulation (PubMed:9796923). Mice are prone to development of autoimmune diseases (PubMed:10485649, PubMed:11209085). In a C57BL/6J background, mice spontaneously develop lupus-like autoimmune phenotypes, characterized by proliferative arthritis and glomerulonephritis with predominant IgG3 deposition (PubMed:10485649). In a BALB/c background, mice develop autoimmune dilated cardiomyopathy with severely impaired contraction, and two-third of mice die by congestive heart failure before 30 weeks of age (PubMed:11209085). Mice lacking both Lag3 and Pdcd1/PD-1 die of severe myocarditis before 10 weeks of age in BALB/c mice (PubMed:21300912). {ECO:0000269|PubMed:10485649, ECO:0000269|PubMed:11209085, ECO:0000269|PubMed:21300912, ECO:0000269|PubMed:9796923}.

Annotations taken from UniProtKB at the EBI.


Organism:		Mus musculus (Mouse).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus.



Function:		Inhibitory receptor on antigen activated T-cells that plays a critical role in induction and maintenance of immune tolerance to self (PubMed:10485649, PubMed:11698646, PubMed:11209085, PubMed:21300912). Delivers inhibitory signals upon binding to ligands, such as CD274/PDCD1L1 and CD273/PDCD1LG2 (PubMed:11015443, PubMed:11224527, PubMed:22641383, PubMed:18287011, PubMed:18641123). Following T-cell receptor (TCR) engagement, PDCD1 associates with CD3-TCR in the immunological synapse and directly inhibits T-cell activation (PubMed:22641383). Suppresses T-cell activation through the recruitment of PTPN11/SHP-2: following ligand-binding, PDCD1 is phosphorylated within the ITSM motif, leading to the recruitment of the protein tyrosine phosphatase PTPN11/SHP-2 that mediates dephosphorylation of key TCR proximal signaling molecules, such as ZAP70, PRKCQ/PKCtheta and CD247/CD3zeta (PubMed:11698646, PubMed:22641383). The PDCD1-mediated inhibitory pathway is exploited by tumors to attenuate anti-tumor immunity and facilitate tumor survival (By similarity). {ECO:0000250\|UniProtKB:Q15116, ECO:0000269\|PubMed:10485649, ECO:0000269\|PubMed:11015443, ECO:0000269\|PubMed:11209085, ECO:0000269\|PubMed:11224527, ECO:0000269\|PubMed:11698646, ECO:0000269\|PubMed:18287011, ECO:0000269\|PubMed:18641123, ECO:0000269\|PubMed:21300912, ECO:0000269\|PubMed:22641383}.


Subunit:		Monomer (PubMed:15030777, PubMed:18287011, PubMed:18641123). Interacts with CD274/PDCD1L1 (PubMed:18287011). Interacts with CD273/PDCD1LG2 (PubMed:18641123). Interacts with FBXO38; leading to ubiquitination and degradation by the proteasome (By similarity). {ECO:0000250\|UniProtKB:Q15116, ECO:0000269\|PubMed:15030777, ECO:0000269\|PubMed:18287011, ECO:0000269\|PubMed:18641123}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:22641383, ECO:0000269\|PubMed:30487606}; Single-pass type I membrane protein.
Tissue specificity:		Thymus-specific. {ECO:0000269\|PubMed:1396582}.
Developmental stage:		Induced at programmed cell death. {ECO:0000269\|PubMed:1396582}.
Ptm:		Ubiquitinated at Lys-235 by the SCF(FBXO38) complex, leading to its proteasomal degradation. Ubiquitinated via 'Lys-48'-linked polyubiquitin chains. {ECO:0000250\|UniProtKB:Q15116}.
Ptm:		Tyrosine phosphorylated at Tyr-225 (within ITIM motif) and Tyr-248 (ITSM motif) upon ligand binding (PubMed:11698646, PubMed:22641383). Phosphorylation at Tyr-248 promotes the recruitment of the protein tyrosine phosphatase PTPN11/SHP-2 that mediates dephosphorylation of key TCR proximal signaling molecules, such as ZAP70, PRKCQ/PKCtheta and CD247/CD3zeta (PubMed:22641383). {ECO:0000269\|PubMed:11698646, ECO:0000269\|PubMed:22641383}.
Disruption phenotype:		Mice grow and develop normally but exhibit splenomegaly, selective augmentation of IgG3 antibody response to a T- independent type II antigen, and enhanced proliferative responses of B- cells and myeloid cells by anti-IgM and granulocyte colony-stimulating factor stimulation (PubMed:9796923). Mice are prone to development of autoimmune diseases (PubMed:10485649, PubMed:11209085). In a C57BL/6J background, mice spontaneously develop lupus-like autoimmune phenotypes, characterized by proliferative arthritis and glomerulonephritis with predominant IgG3 deposition (PubMed:10485649). In a BALB/c background, mice develop autoimmune dilated cardiomyopathy with severely impaired contraction, and two-third of mice die by congestive heart failure before 30 weeks of age (PubMed:11209085). Mice lacking both Lag3 and Pdcd1/PD-1 die of severe myocarditis before 10 weeks of age in BALB/c mice (PubMed:21300912). {ECO:0000269\|PubMed:10485649, ECO:0000269\|PubMed:11209085, ECO:0000269\|PubMed:21300912, ECO:0000269\|PubMed:9796923}.