NECTIN4 (poliovirus receptor-related 4)

2008-01-01 Marc Lopez Affiliation

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

Identity

HGNC

NECTIN4

LOCATION

1q23.3

LOCUSID

81607

ALIAS

EDSS1,LNIR,PRR4,PVRL4,nectin-4

FUSION GENES

Show Gene Fusions

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.

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.

Oncogenesis

Related to tumor cell migration.

Bibliography

Pubmed ID	Last Year	Title	Authors
12011057	2002	Prominent 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
17474988	2007	Nectin-4 is a new histological and serological tumor associated marker for breast cancer.	Fabre-Lafay S et al
11544254	2001	Nectin4/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 ID	Transcript ID	Uniprot
ENSG00000143217	ENST00000368012	Q96NY8
ENSG00000143217	ENST00000368012	K4PZ75

Expression (GTEx)

100

150

200

250

Adipose - Subcutaneous

Adipose - Visceral

Adrenal Gland

Artery - Aorta

Artery - Tibial

Bladder

Brain - Amygdala

Brain - Anterior cingulate cortex

Brain - Caudate

Brain - Cerebellar Hemisphere

Brain - Cerebellum

Brain - Cortex

Brain - Frontal Cortex

Brain - Hippocampus

Brain - Hypothalamus

Brain - Nucleus accumbens

Brain - Putamen

Brain - Spinal cord

Brain - Substantia nigra

Breast - Mammary Tissue

Cells - Cultured fibroblasts

Cells - EBV - transformed lymphocytes

Cervix - Ectocervix

Cervix - Endocervix

Colon - Sigmoid

Colon - Transverse

Esophagus - Gastroesophageal Junction

Esophagus - Mucosa

Esophagus - Muscularis

Fallopian Tube

Heart - Atrial Appendage

Heart - Left Ventricle

Kidney - Cortex

Kidney - Medulla

Liver

Lung

Minor Salivary Gland

Muscle - Skeletal

Nerve - Tibial

Ovary

Pancreas

Pituitary

Prostate

Skin - Not Sun Exposed

Skin - Sun Exposed

Small Intestine - Terminal Ileum

Spleen

Stomach

Testis

Thyroid

Uterus

Vagina

Whole Blood

Pathways

Pathway	Source	External ID
Adherens junction	KEGG	ko04520
Adherens junction	KEGG	hsa04520
Cell-Cell communication	REACTOME	R-HSA-1500931
Cell junction organization	REACTOME	R-HSA-446728
Cell-cell junction organization	REACTOME	R-HSA-421270
Adherens junctions interactions	REACTOME	R-HSA-418990
Nectin/Necl trans heterodimerization	REACTOME	R-HSA-420597

Protein levels (Protein atlas)

Not detected

Low

Medium

High

PharmGKB

Entity ID	Name	Type	Evidence	Association	PK	PD	PMIDs
PA166190121	enfortumab vedotin	Chemical	LabelAnnotation	associated

References

Pubmed ID	Year	Title	Citations
22048310	2011	Adherens junction protein nectin-4 is the epithelial receptor for measles virus.	227
21901103	2011	Tumor cell marker PVRL4 (nectin 4) is an epithelial cell receptor for measles virus.	211
19679554	2009	Identification of nectin-4 oncoprotein as a diagnostic and therapeutic target for lung cancer.	60
20959669	2010	Nectin 4 overexpression in ovarian cancer tissues and serum: potential role as a serum biomarker.	58
15784625	2005	Nectin-4, a new serological breast cancer marker, is a substrate for tumor necrosis factor-alpha-converting enzyme (TACE)/ADAM-17.	54
17474988	2007	Nectin-4 is a new histological and serological tumor associated marker for breast cancer.	45
23202587	2013	Structure of measles virus hemagglutinin bound to its epithelial receptor nectin-4.	44
27013195	2016	Enfortumab Vedotin Antibody-Drug Conjugate Targeting Nectin-4 Is a Highly Potent Therapeutic Agent in Multiple Preclinical Cancer Models.	35
23682311	2013	A role for PVRL4-driven cell-cell interactions in tumorigenesis.	33
20691405	2010	Mutations in PVRL4, encoding cell adhesion molecule nectin-4, cause ectodermal dysplasia-syndactyly syndrome.	27

Citation

Marc Lopez

NECTIN4 (poliovirus receptor-related 4)

Atlas Genet Cytogenet Oncol Haematol. 2008-01-01

Online version: http://atlasgeneticsoncology.org/gene/44141/nectin4