NECTIN4 (poliovirus receptor-related 4)

2008-01-01   Marc Lopez  

Centre de Recherches en Cancérologie de Marseille, Inserm UMR599, 27 bvd Leiroure,13009 Marseille, France

Identity

HGNC
LOCATION
1q23.3
LOCUSID
ALIAS
EDSS1,LNIR,PRR4,PVRL4,nectin-4
FUSION GENES

DNA/RNA

Description

The PVRL4 gene spans 17.85 kb, consists of 9 exons and 8 introns.

Transcription

The human Nectin-4 mRNA consists of 1458 or 1533 bases (alternative splice forms).

Proteins

Note

Nectin-4 belongs to the family of adhesion molecules: Nectins. Four members have been described ( Nectin-1, Nectin-2, Nectin-3 and Nectin-4). Nectins belong to the immunoglobulin superfamily and exhibit three Ig-like domain in their extracellular region.
Atlas Image
Extracellular region of dimeric Nectin-4 is composed with three Ig domains of Ig V and IgC types. The last 4 aminoacids in the C-terminus region binds to the scaffold F-actin binding protein AF-6/afadin. Nectin-4 ectodomain is shedded from cell surface by the metalloprotease TACE/ ADAM-17.

Description

Nectin-4 protein is 510 aminoacid long. Molecular weight is 66 kDa.

Expression

Nectin-4 expression in mainly expressed during development. In mice Nectin-4 transcript are detected at day 11 d.p.c. In human Nectin-4 is not expressed in adult tissues.

Localisation

Nectin-4 is expressed at epithelial adherens junctions. In tumors Nectin-4 expression can be observed in the cytoplasm.

Function

Nectin-4 binds Nectin-1 through IgV domain interaction. Nectin-1 is involved in development. Nectin-4 increases tumor cell migration.

Homology

With other members of the family.

Implicated in

Entity name
Breast carcinoma of basal subtypes.
Disease
Nectin-4 is found in breast tumors and its expression correlates with the basal subtype. The soluble form is detected in sera of patients with metastatic breast carcinoma and is a marker of disease progression.
Prognosis
Adverse prognosis.
Atlas Image
Oncogenesis
Related to tumor cell migration.

Article Bibliography

Pubmed IDLast YearTitleAuthors
120110572002Prominent role of the Ig-like V domain in trans-interactions of nectins. Nectin3 and nectin 4 bind to the predicted C-C'-C"-D beta-strands of the nectin1 V domain.Fabre S et al
174749882007Nectin-4 is a new histological and serological tumor associated marker for breast cancer.Fabre-Lafay S et al
115442542001Nectin4/PRR4, a new afadin-associated member of the nectin family that trans-interacts with nectin1/PRR1 through V domain interaction.Reymond N et al

Other Information

Locus ID:

NCBI: 81607
MIM: 609607
HGNC: 19688
Ensembl: ENSG00000143217

Variants:

dbSNP: 81607
ClinVar: 81607
TCGA: ENSG00000143217
COSMIC: NECTIN4

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000143217ENST00000368012Q96NY8
ENSG00000143217ENST00000368012K4PZ75

Expression (GTEx)

0
50
100
150
200
250

Pathways

PathwaySourceExternal ID
Adherens junctionKEGGko04520
Adherens junctionKEGGhsa04520
Cell-Cell communicationREACTOMER-HSA-1500931
Cell junction organizationREACTOMER-HSA-446728
Cell-cell junction organizationREACTOMER-HSA-421270
Adherens junctions interactionsREACTOMER-HSA-418990
Nectin/Necl trans heterodimerizationREACTOMER-HSA-420597

Protein levels (Protein atlas)

Not detected
Low
Medium
High

PharmGKB

Entity IDNameTypeEvidenceAssociationPKPDPMIDs
PA166190121enfortumab vedotinChemicalLabelAnnotationassociated

References

Pubmed IDYearTitleCitations
380632702024Expression of PVRL4, a molecular target for cancer treatment, is transcriptionally regulated by FOS.1
381962022024Associations of TACSTD2/TROP2 and NECTIN-4/NECTIN-4 with molecular subtypes, PD-L1 expression, and FGFR3 mutational status in two advanced urothelial bladder cancer cohorts.2
380632702024Expression of PVRL4, a molecular target for cancer treatment, is transcriptionally regulated by FOS.1
381962022024Associations of TACSTD2/TROP2 and NECTIN-4/NECTIN-4 with molecular subtypes, PD-L1 expression, and FGFR3 mutational status in two advanced urothelial bladder cancer cohorts.2
365851802023Immunohistochemical Analysis of HER2, EGFR, and Nectin-4 Expression in Upper Urinary Tract Urothelial Carcinoma.2
367597212023Trop-2 and Nectin-4 immunohistochemical expression in metastatic colorectal cancer: searching for the right population for drugs' development.4
371831492023A novel homozygous nonsense mutation in NECTIN4 gene in a Pakistani family with ectodermal dysplasia syndactyly syndrome 1.1
378291542023A Recurrent Nonsense Mutation in NECTIN4 Underlying Ectodermal Dysplasia-Syndactyly Syndrome with a Novel Phenotype in a Consanguineous Kashmiri Family.0
380621062023Nectin-4 regulates cellular senescence-associated enlargement of cell size.0
365851802023Immunohistochemical Analysis of HER2, EGFR, and Nectin-4 Expression in Upper Urinary Tract Urothelial Carcinoma.2
367597212023Trop-2 and Nectin-4 immunohistochemical expression in metastatic colorectal cancer: searching for the right population for drugs' development.4
371831492023A novel homozygous nonsense mutation in NECTIN4 gene in a Pakistani family with ectodermal dysplasia syndactyly syndrome 1.1
378291542023A Recurrent Nonsense Mutation in NECTIN4 Underlying Ectodermal Dysplasia-Syndactyly Syndrome with a Novel Phenotype in a Consanguineous Kashmiri Family.0
380621062023Nectin-4 regulates cellular senescence-associated enlargement of cell size.0
352566872022Nectin cell adhesion molecule 4 regulates angiogenesis through Src signaling and serves as a novel therapeutic target in angiosarcoma.3

Citation

Marc Lopez

NECTIN4 (poliovirus receptor-related 4)

Atlas Genet Cytogenet Oncol Haematol. 2008-01-01

Online version: http://atlasgeneticsoncology.org/gene/44141/favicon/meetings/case-report-explorer/