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    NECTIN3 nectin cell adhesion molecule 3 [ Homo sapiens (human) ]

    Gene ID: 25945, updated on 28-Oct-2024

    Summary

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    Official Symbol
    NECTIN3provided by HGNC
    Official Full Name
    nectin cell adhesion molecule 3provided by HGNC
    Primary source
    HGNC:HGNC:17664
    See related
    Ensembl:ENSG00000177707 MIM:607147; AllianceGenome:HGNC:17664
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    PPR3; PRR3; CD113; PVRL3; PVRR3; CDW113; NECTIN-3
    Summary
    This gene encodes a member of the nectin family of proteins, which function as adhesion molecules at adherens junctions. This family member interacts with other nectin-like proteins and with afadin, a filamentous actin-binding protein involved in the regulation of directional motility, cell proliferation and survival. This gene plays a role in ocular development involving the ciliary body. Mutations in this gene are believed to result in congenital ocular defects. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]
    Expression
    Broad expression in thyroid (RPKM 7.4), testis (RPKM 7.4) and 22 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See NECTIN3 in Genome Data Viewer
    Location:
    3q13.13
    Exon count:
    12
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (111071816..111194170)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (113792242..113914605)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (110790663..110913017)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene OCT4-NANOG-H3K27ac hESC enhancer GRCh37_chr3:110404170-110404746 Neighboring gene ribosomal protein SA pseudogene 29 Neighboring gene OCT4-NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:110607916-110608531 Neighboring gene putative uncharacterized protein LOC151760 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr3:110683374-110684573 Neighboring gene MED14-independent group 3 enhancer GRCh37_chr3:110764172-110765371 Neighboring gene NECTIN3 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14597 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr3:110929660-110930290 Neighboring gene uncharacterized LOC124909493 Neighboring gene uncharacterized LOC105374038

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. Nectin-3 is a new biomarker that mediates the upregulation of MMP2 and MMP9 in ovarian cancer cells. Xu F, et al. Biomed Pharmacother, 2019 Feb. PMID 30469078
    2. Binding and entry of Clostridium difficile toxin B is mediated by multiple domains. Manse JS, et al. FEBS Lett, 2015 Dec 21. PMID 26602083
    3. Differential gene expression of primary cultured lymphatic and blood vascular endothelial cells. Nelson GM, et al. Neoplasia, 2007 Dec. PMID 18084611, Free PMC Article
    4. Molecular analysis of germline t(3;6) and t(3;12) associated with conventional renal cell carcinomas indicates their rate-limiting role and supports the three-hit model of carcinogenesis. Yusenko MV, et al. Cancer Genet Cytogenet, 2010 Aug. PMID 20633763
    5. Loss of nectin-3 expression as a marker of tumor aggressiveness in pancreatic neuroendocrine tumor. Hirabayashi K, et al. Pathol Int, 2020 Feb. PMID 31855317

    See all (60) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Loss of nectin-3 expression as a marker of tumor aggressiveness in pancreatic neuroendocrine tumor.
      Title: Loss of nectin-3 expression as a marker of tumor aggressiveness in pancreatic neuroendocrine tumor.
    2. Nectin-3 expression was associated with ovarian cancer, and a greater expression level of nectin-3 was related to poor overall survival.
      Title: Nectin-3 is a new biomarker that mediates the upregulation of MMP2 and MMP9 in ovarian cancer cells.
    3. Nectin-3 mutation in men with severe teratospermia
      Title: Detection of candidate nectin gene mutations in infertile men with severe teratospermia.
    4. Data suggest that 3 independent regions of TcdB (Clostridium difficile toxin B; 1372-1493, 1493-1848, 1851-2366) contribute to binding and entry of TcdB into mammalian cells; residues 1372-1493 are sufficient for interaction with PVRL3.
      Title: Binding and entry of Clostridium difficile toxin B is mediated by multiple domains.
    5. Expression of nectin-3 in pancreatic cancer can be a prognostic factor.
      Title: Nectin expression in pancreatic adenocarcinoma: nectin-3 is associated with a poor prognosis.
    6. PVRL3 is a physiologically relevant binding partner that can serve as a target for the prevention of TcdB-induced cytotoxicity in C. difficile infection.
      Title: Identification of an epithelial cell receptor responsible for Clostridium difficile TcdB-induced cytotoxicity.
    7. Nectin-3 is associated with the formation of cell junctions and be a putative suppressor molecule to the invasion of breast cancer cells.
      Title: The expression of the Nectin complex in human breast cancer and the role of Nectin-3 in the control of tight junctions during metastasis.
    8. Nectin-3 trans-interacts with Nectin-2 to promote lymphocyte and monocyte extravasation.
      Title: Nectin-3 (CD113) interacts with Nectin-2 (CD112) to promote lymphocyte transendothelial migration.
    9. Data suggest that expression of nectin-3 is up-regulated in eutopic endometrium of patients with endometriosis as compared with control subjects and up-regulated in all endometriotic lesions investigated compared with eutopic endometrium.
      Title: Eutopic endometrium and peritoneal, ovarian and colorectal endometriotic tissues express a different profile of nectin-1, -3, -4 and nectin-like molecule 2.
    10. Observational study of gene-disease association, gene-environment interaction, and pharmacogenomic / toxicogenomic. (HuGE Navigator)
      Title: Variation at the NFATC2 locus increases the risk of thiazolidinedione-induced edema in the Diabetes REduction Assessment with ramipril and rosiglitazone Medication (DREAM) study.
    Submit: New GeneRIF Correction See all GeneRIFs (11)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    HIV-1 infection (VSV-G pseudotyped) of CEMT4 T cells downregulates plasma membrane expression of NECTIN3 PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Tat tat HIV-1 Tat downregulates the expression of poliovirus receptor-related 3 (PVRL3) in human primary T cells PubMed

    Go to the HIV-1, Human Interaction Database

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ90624, DKFZp566B0846

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables cell adhesion molecule binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein homodimerization activity ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    Process Evidence Code Pubs
    involved_in establishment of protein localization to plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in fertilization IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in homophilic cell adhesion via plasma membrane adhesion molecules IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in homophilic cell adhesion via plasma membrane adhesion molecules ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    involved_in lens morphogenesis in camera-type eye IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in protein localization to cell junction IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in regulation of postsynapse assembly IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in retina morphogenesis in camera-type eye IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in symbiont entry into host cell IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    is_active_in adherens junction IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    is_active_in apical junction complex IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in axon IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cell-cell contact zone IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in cell-cell junction ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in dendrite IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in hippocampal mossy fiber to CA3 synapse IEA
    Inferred from Electronic Annotation
    more info
    		  
    located_in plasma membrane ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    located_in plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    located_in postsynaptic density membrane IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    nectin-3
    Names
    nectin 3
    poliovirus receptor-related 3
    poliovirus receptor-related protein 3

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_029835.1 RefSeqGene

      Range
      5058..70802
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001243286.2 → NP_001230215.1  nectin-3 isoform 2 precursor

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) uses an alternate splice site that results in a frameshift in the 3' coding region, compared to variant 1. The encoded isoform (2) has a distinct and shorter C-terminus, compared to isoform 1.
      Source sequence(s)
      AA555086, AC133477, AC137833, BC067808, BI464010
      Consensus CDS
      CCDS58842.1
      UniProtKB/Swiss-Prot
      Q9NQS3
      Related
      ENSP00000321514.3, ENST00000319792.7
      Conserved Domains (4) summary
      cd00096
      Location:269 → 275
      Ig; Ig strand A [structural motif]
      cd05887
      Location:58 → 167
      IgV_1_Nectin-3_like; First immunoglobulin variable (IgV) domain of nectin-3 (also known as poliovirus receptor related protein 3), and similar domains
      cd07704
      Location:170 → 265
      IgC1_2_Nectin-3-4_like; Second immunoglobulin (Ig) domain of nectin-3 and nectin-4 (poliovirus receptor related protein 4), and similar domains; member of the C1-set of Ig superfamily (IgSF) domains
      cl11960
      Location:269 → 355
      Ig; Immunoglobulin domain

    2. NM_001243288.2 → NP_001230217.1  nectin-3 isoform 3

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR and 5' coding region, uses a distinct start codon, and has alternate exon structure in the 3' coding region and 3' UTR, compared to variant 1. The encoded isoform (3) has distinct N- and C-termini and is shorter than isoform 1.
      Source sequence(s)
      AC133436, AC133477, AK075105, BQ025085
      Consensus CDS
      CCDS58843.1
      UniProtKB/Swiss-Prot
      Q9NQS3
      Related
      ENSP00000420579.1, ENST00000493615.5
      Conserved Domains (4) summary
      cd05887
      Location:49 → 144
      Ig1_Nectin-3_like; First immunoglobulin (Ig) domain of nectin-3 (also known as poliovirus receptor related protein 3) and similar proteins
      smart00410
      Location:41 → 143
      IG_like; Immunoglobulin like
      pfam13927
      Location:264 → 319
      Ig_3; Immunoglobulin domain
      cl11960
      Location:147 → 242
      Ig; Immunoglobulin domain

    3. NM_015480.3 → NP_056295.1  nectin-3 isoform 1 precursor

      See identical proteins and their annotated locations for NP_056295.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AA555086, AC137833, AF282874, BI464010
      Consensus CDS
      CCDS2957.1
      UniProtKB/Swiss-Prot
      E9PFR0, Q6NVZ3, Q8NC05, Q8WVU4, Q9BVA9, Q9NQS3, Q9Y412
      Related
      ENSP00000418070.1, ENST00000485303.6
      Conserved Domains (5) summary
      cd12087
      Location:404 → 432
      TM_EGFR-like; Transmembrane domain of the Epidermal Growth Factor Receptor family of Protein Tyrosine Kinases
      cd00096
      Location:269 → 275
      Ig; Ig strand A [structural motif]
      cd05887
      Location:58 → 167
      IgV_1_Nectin-3_like; First immunoglobulin variable (IgV) domain of nectin-3 (also known as poliovirus receptor related protein 3), and similar domains
      cd07704
      Location:170 → 265
      IgC1_2_Nectin-3-4_like; Second immunoglobulin (Ig) domain of nectin-3 and nectin-4 (poliovirus receptor related protein 4), and similar domains; member of the C1-set of Ig superfamily (IgSF) domains
      cl11960
      Location:269 → 355
      Ig; Immunoglobulin domain

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      111071816..111194170
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_017006123.2 → XP_016861612.1  nectin-3 isoform X2

    2. XM_017006126.2 → XP_016861615.1  nectin-3 isoform X5

    3. XM_017006125.2 → XP_016861614.1  nectin-3 isoform X4

    4. XM_011512663.2 → XP_011510965.1  nectin-3 isoform X1

      Conserved Domains (5) summary
      cd05887
      Location:103 → 198
      Ig1_Nectin-3_like; First immunoglobulin (Ig) domain of nectin-3 (also known as poliovirus receptor related protein 3) and similar proteins
      cd12087
      Location:435 → 463
      TM_EGFR-like; Transmembrane domain of the Epidermal Growth Factor Receptor family of Protein Tyrosine Kinases
      smart00410
      Location:95 → 197
      IG_like; Immunoglobulin like
      pfam13927
      Location:318 → 373
      Ig_3; Immunoglobulin domain
      cl11960
      Location:201 → 296
      Ig; Immunoglobulin domain

    5. XM_047447934.1 → XP_047303890.1  nectin-3 isoform X6

    6. XM_017006127.3 → XP_016861616.1  nectin-3 isoform X6

      Conserved Domains (4) summary
      cd12087
      Location:192 → 220
      TM_EGFR-like; Transmembrane domain of the Epidermal Growth Factor Receptor family of Protein Tyrosine Kinases
      smart00410
      Location:75 → 136
      IG_like; Immunoglobulin like
      pfam13927
      Location:75 → 130
      Ig_3; Immunoglobulin domain
      cl11960
      Location:1 → 53
      Ig; Immunoglobulin domain

    7. XM_017006124.2 → XP_016861613.1  nectin-3 isoform X3

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      113792242..113914605
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054346112.1 → XP_054202087.1  nectin-3 isoform X2

    2. XM_054346115.1 → XP_054202090.1  nectin-3 isoform X5

    3. XM_054346114.1 → XP_054202089.1  nectin-3 isoform X4

    4. XM_054346111.1 → XP_054202086.1  nectin-3 isoform X1

    5. XM_054346116.1 → XP_054202091.1  nectin-3 isoform X6

    6. XM_054346113.1 → XP_054202088.1  nectin-3 isoform X3

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9NQS3.1 GenPept UniProtKB/Swiss-Prot:Q9NQS3

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