UniProt functional annotation for Q9NQS3



	UniProt functional annotation for Q9NQS3

UniProt code: Q9NQS3.

Organism: Homo sapiens (Human).

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

Function: Plays a role in cell-cell adhesion through heterophilic trans-interactions with nectin-like proteins or nectins, such as trans- interaction with NECTIN2 at Sertoli-spermatid junctions. Trans- interaction with PVR induces activation of CDC42 and RAC small G proteins through common signaling molecules such as SRC and RAP1. Also involved in the formation of cell-cell junctions, including adherens junctions and synapses. Induces endocytosis-mediated down-regulation of PVR from the cell surface, resulting in reduction of cell movement and proliferation. Plays a role in the morphology of the ciliary body. {ECO:0000269|PubMed:16216929}.

Subunit: Cis- and trans-homodimer. Can form trans-heterodimers with NECTIN1, NECTIN2, PVR, IGSF4B/Necl-1 and with IGSF4. Interaction between NECTIN1 and NECTIN3 on the pre- and postsynaptic sites, respectively, initiates the formation of puncta adherentia junctions between axons and dendrites. Interacts (via Cytoplasmic domain) with AFDN, providing a connection with the actin cytoskeleton. Binds with low affinity to TIGIT. {ECO:0000269|PubMed:11024295, ECO:0000269|PubMed:12759359, ECO:0000269|PubMed:16216929, ECO:0000269|PubMed:19011627, ECO:0000269|PubMed:22902367}.

Subunit: (Microbial infection) Interacts with C.difficile toxin TcdB, suggesting that it may contribute to TcdB toxin entry into cells (PubMed:26038560). It was however shown that NECTIN3/PVRL3 does not act as a major receptor for TcdB (PubMed:27680706). {ECO:0000269|PubMed:26038560, ECO:0000269|PubMed:27680706}.

Subcellular location: Cell membrane {ECO:0000269|PubMed:26038560}; Single-pass membrane protein {ECO:0000255}. Cell junction, synapse, postsynaptic cell membrane {ECO:0000250}.

Tissue specificity: Predominantly expressed in testis and placenta as well as in many cell lines, including epithelial cell lines. {ECO:0000269|PubMed:11024295}.

Similarity: Belongs to the nectin family. {ECO:0000305}.

Sequence caution: [Isoform 1]: Sequence=AAH17572.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Sequence caution: [Isoform 3]: Sequence=BAC11404.1; Type=Erroneous termination; Note=Truncated C-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 role in cell-cell adhesion through heterophilic trans-interactions with nectin-like proteins or nectins, such as trans- interaction with NECTIN2 at Sertoli-spermatid junctions. Trans- interaction with PVR induces activation of CDC42 and RAC small G proteins through common signaling molecules such as SRC and RAP1. Also involved in the formation of cell-cell junctions, including adherens junctions and synapses. Induces endocytosis-mediated down-regulation of PVR from the cell surface, resulting in reduction of cell movement and proliferation. Plays a role in the morphology of the ciliary body. {ECO:0000269\|PubMed:16216929}.


Subunit:		Cis- and trans-homodimer. Can form trans-heterodimers with NECTIN1, NECTIN2, PVR, IGSF4B/Necl-1 and with IGSF4. Interaction between NECTIN1 and NECTIN3 on the pre- and postsynaptic sites, respectively, initiates the formation of puncta adherentia junctions between axons and dendrites. Interacts (via Cytoplasmic domain) with AFDN, providing a connection with the actin cytoskeleton. Binds with low affinity to TIGIT. {ECO:0000269\|PubMed:11024295, ECO:0000269\|PubMed:12759359, ECO:0000269\|PubMed:16216929, ECO:0000269\|PubMed:19011627, ECO:0000269\|PubMed:22902367}.
Subunit:		(Microbial infection) Interacts with C.difficile toxin TcdB, suggesting that it may contribute to TcdB toxin entry into cells (PubMed:26038560). It was however shown that NECTIN3/PVRL3 does not act as a major receptor for TcdB (PubMed:27680706). {ECO:0000269\|PubMed:26038560, ECO:0000269\|PubMed:27680706}.
Subcellular location:		Cell membrane {ECO:0000269\|PubMed:26038560}; Single-pass membrane protein {ECO:0000255}. Cell junction, synapse, postsynaptic cell membrane {ECO:0000250}.
Tissue specificity:		Predominantly expressed in testis and placenta as well as in many cell lines, including epithelial cell lines. {ECO:0000269\|PubMed:11024295}.
Similarity:		Belongs to the nectin family. {ECO:0000305}.
Sequence caution:		[Isoform 1]: Sequence=AAH17572.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
Sequence caution:		[Isoform 3]: Sequence=BAC11404.1; Type=Erroneous termination; Note=Truncated C-terminus.; Evidence={ECO:0000305};