UniProt functional annotation for Q9NZQ7



	UniProt functional annotation for Q9NZQ7

UniProt code: Q9NZQ7.

Organism: Homo sapiens (Human).

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

Function: Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813417, PubMed:28813410). As a ligand for the inhibitory receptor PDCD1/PD-1, modulates the activation threshold of T-cells and limits T-cell effector response (PubMed:11015443, PubMed:28813417, PubMed:28813410). Through a yet unknown activating receptor, may costimulate T-cell subsets that predominantly produce interleukin-10 (IL10) (PubMed:10581077). {ECO:0000269|PubMed:10581077, ECO:0000269|PubMed:11015443, ECO:0000269|PubMed:28813410, ECO:0000269|PubMed:28813417}.

Function: The PDCD1-mediated inhibitory pathway is exploited by tumors to attenuate anti-tumor immunity and escape destruction by the immune system, thereby facilitating tumor survival (PubMed:28813417, PubMed:28813410). The interaction with PDCD1/PD-1 inhibits cytotoxic T lymphocytes (CTLs) effector function (By similarity). The blockage of the PDCD1-mediated pathway results in the reversal of the exhausted T- cell phenotype and the normalization of the anti-tumor response, providing a rationale for cancer immunotherapy (By similarity). {ECO:0000250|UniProtKB:Q9EP73, ECO:0000269|PubMed:28813410, ECO:0000269|PubMed:28813417}.

Subunit: Interacts with PDCD1 (PubMed:11015443, PubMed:18287011, PubMed:26602187). Interacts (via transmembrane domain) with CMTM4 and CMTM6 (PubMed:28813417, PubMed:28813410). {ECO:0000269|PubMed:11015443, ECO:0000269|PubMed:18287011, ECO:0000269|PubMed:26602187, ECO:0000269|PubMed:28813410, ECO:0000269|PubMed:28813417}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:28813410, ECO:0000269|PubMed:28813417}; Single-pass type I membrane protein {ECO:0000255}. Early endosome membrane {ECO:0000269|PubMed:28813417}; Single-pass type I membrane protein {ECO:0000255}. Recycling endosome membrane {ECO:0000269|PubMed:28813417}; Single-pass type I membrane protein {ECO:0000255}. Note=Associates with CMTM6 at recycling endosomes, where it is protected from being targeted for lysosomal degradation. {ECO:0000269|PubMed:28813417}.

Subcellular location: [Isoform 1]: Cell membrane {ECO:0000269|PubMed:15780196}; Single-pass type I membrane protein {ECO:0000255}.

Subcellular location: [Isoform 2]: Endomembrane system {ECO:0000269|PubMed:15780196}; Single-pass type I membrane protein {ECO:0000255}.

Tissue specificity: Highly expressed in the heart, skeletal muscle, placenta and lung. Weakly expressed in the thymus, spleen, kidney and liver. Expressed on activated T- and B-cells, dendritic cells, keratinocytes and monocytes. {ECO:0000269|PubMed:10581077, ECO:0000269|PubMed:11015443}.

Induction: Up-regulated on T- and B-cells, dendritic cells, keratinocytes and monocytes after LPS and IFNG activation. Up-regulated in B-cells activated by surface Ig cross-linking. {ECO:0000269|PubMed:10581077, ECO:0000269|PubMed:11015443, ECO:0000269|PubMed:28813410}.

Ptm: Ubiquitinated; STUB1 likely mediates polyubiquitination of PD- L1/CD274 triggering its degradation. {ECO:0000269|PubMed:28813410}.

Disease: Note=Truncation of the 3'-untranslated (3'-UTR) region of CD274 transcripts leads to elevated expression of CD274 in multiple cancers including T-cell leukemia, diffuse large B-cell lymphoma and stomach adenocarcinoma (PubMed:27281199). Disruption of 3'-UTR region is caused by structural variants that stabilize CD274 transcripts, leading to overexpression (PubMed:27281199). Increased expression in tumors promotes immune evasion and tumor cell growth by allowing malignant cells to escape destruction by the immune system (PubMed:27281199). {ECO:0000269|PubMed:27281199}.

Miscellaneous: [Isoform 3]: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. {ECO:0000305}.

Similarity: Belongs to the immunoglobulin superfamily. BTN/MOG family. {ECO:0000305}.

Sequence caution: Sequence=BAA91966.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={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:		Plays a critical role in induction and maintenance of immune tolerance to self (PubMed:11015443, PubMed:28813417, PubMed:28813410). As a ligand for the inhibitory receptor PDCD1/PD-1, modulates the activation threshold of T-cells and limits T-cell effector response (PubMed:11015443, PubMed:28813417, PubMed:28813410). Through a yet unknown activating receptor, may costimulate T-cell subsets that predominantly produce interleukin-10 (IL10) (PubMed:10581077). {ECO:0000269\|PubMed:10581077, ECO:0000269\|PubMed:11015443, ECO:0000269\|PubMed:28813410, ECO:0000269\|PubMed:28813417}.



Function:		The PDCD1-mediated inhibitory pathway is exploited by tumors to attenuate anti-tumor immunity and escape destruction by the immune system, thereby facilitating tumor survival (PubMed:28813417, PubMed:28813410). The interaction with PDCD1/PD-1 inhibits cytotoxic T lymphocytes (CTLs) effector function (By similarity). The blockage of the PDCD1-mediated pathway results in the reversal of the exhausted T- cell phenotype and the normalization of the anti-tumor response, providing a rationale for cancer immunotherapy (By similarity). {ECO:0000250\|UniProtKB:Q9EP73, ECO:0000269\|PubMed:28813410, ECO:0000269\|PubMed:28813417}.


Subunit:		Interacts with PDCD1 (PubMed:11015443, PubMed:18287011, PubMed:26602187). Interacts (via transmembrane domain) with CMTM4 and CMTM6 (PubMed:28813417, PubMed:28813410). {ECO:0000269\|PubMed:11015443, ECO:0000269\|PubMed:18287011, ECO:0000269\|PubMed:26602187, ECO:0000269\|PubMed:28813410, ECO:0000269\|PubMed:28813417}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:28813410, ECO:0000269\|PubMed:28813417}; Single-pass type I membrane protein {ECO:0000255}. Early endosome membrane {ECO:0000269\|PubMed:28813417}; Single-pass type I membrane protein {ECO:0000255}. Recycling endosome membrane {ECO:0000269\|PubMed:28813417}; Single-pass type I membrane protein {ECO:0000255}. Note=Associates with CMTM6 at recycling endosomes, where it is protected from being targeted for lysosomal degradation. {ECO:0000269\|PubMed:28813417}.
Subcellular location:		[Isoform 1]: Cell membrane {ECO:0000269\|PubMed:15780196}; Single-pass type I membrane protein {ECO:0000255}.
Subcellular location:		[Isoform 2]: Endomembrane system {ECO:0000269\|PubMed:15780196}; Single-pass type I membrane protein {ECO:0000255}.
Tissue specificity:		Highly expressed in the heart, skeletal muscle, placenta and lung. Weakly expressed in the thymus, spleen, kidney and liver. Expressed on activated T- and B-cells, dendritic cells, keratinocytes and monocytes. {ECO:0000269\|PubMed:10581077, ECO:0000269\|PubMed:11015443}.
Induction:		Up-regulated on T- and B-cells, dendritic cells, keratinocytes and monocytes after LPS and IFNG activation. Up-regulated in B-cells activated by surface Ig cross-linking. {ECO:0000269\|PubMed:10581077, ECO:0000269\|PubMed:11015443, ECO:0000269\|PubMed:28813410}.
Ptm:		Ubiquitinated; STUB1 likely mediates polyubiquitination of PD- L1/CD274 triggering its degradation. {ECO:0000269\|PubMed:28813410}.
Disease:		Note=Truncation of the 3'-untranslated (3'-UTR) region of CD274 transcripts leads to elevated expression of CD274 in multiple cancers including T-cell leukemia, diffuse large B-cell lymphoma and stomach adenocarcinoma (PubMed:27281199). Disruption of 3'-UTR region is caused by structural variants that stabilize CD274 transcripts, leading to overexpression (PubMed:27281199). Increased expression in tumors promotes immune evasion and tumor cell growth by allowing malignant cells to escape destruction by the immune system (PubMed:27281199). {ECO:0000269\|PubMed:27281199}.
Miscellaneous:		[Isoform 3]: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay. {ECO:0000305}.
Similarity:		Belongs to the immunoglobulin superfamily. BTN/MOG family. {ECO:0000305}.
Sequence caution:		Sequence=BAA91966.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};