NECTIN4

Protein identityUniProt · HPA

UniProt accession

Q96NY8

Gene

NECTIN4

Ensembl

ENSG00000143217

Chromosome

1

Canonical length

510 aa

Protein class

Disease related genes, Human disease related genes, Predicted membrane proteins, Predicted secreted proteins

Subcellular location

Plasma membrane

Secretome location

Secreted in other tissues

OverviewNCBI Gene

This gene encodes a member of the nectin family. The encoded protein contains two immunoglobulin-like (Ig-like) C2-type domains and one Ig-like V-type domain. It is involved in cell adhesion through trans-homophilic and -heterophilic interactions. It is a single-pass type I membrane protein. The soluble form is produced by proteolytic cleavage at the cell surface by the metalloproteinase ADAM17/TACE. The secreted form is found in both breast tumor cell lines and breast tumor patients. Mutations in this gene are the cause of ectodermal dysplasia-syndactyly syndrome type 1, an autosomal recessive disorder. Alternatively spliced transcript variants have been found but the full-length nature of the variant has not been determined.[provided by RefSeq, Jan 2011]

Canonical amino-acid sequenceUniProt

510 residues, UniProt reviewed canonical sequence.

>Q96NY8|NECTIN4
     1  MPLSLGAEMW GPEAWLLLLL LLASFTGRCP AGELETSDVV TVVLGQDAKL PCFYRGDSGE
    61  QVGQVAWARV DAGEGAQELA LLHSKYGLHV SPAYEGRVEQ PPPPRNPLDG SVLLRNAVQA
   121  DEGEYECRVS TFPAGSFQAR LRLRVLVPPL PSLNPGPALE EGQGLTLAAS CTAEGSPAPS
   181  VTWDTEVKGT TSSRSFKHSR SAAVTSEFHL VPSRSMNGQP LTCVVSHPGL LQDQRITHIL
   241  HVSFLAEASV RGLEDQNLWH IGREGAMLKC LSEGQPPPSY NWTRLDGPLP SGVRVDGDTL
   301  GFPPLTTEHS GIYVCHVSNE FSSRDSQVTV DVLDPQEDSG KQVDLVSASV VVVGVIAALL
   361  FCLLVVVVVL MSRYHRRKAQ QMTQKYEEEL TLTRENSIRR LHSHHTDPRS QPEESVGLRA
   421  EGHPDSLKDN SSCSVMSEEP EGRSYSTLTT VREIETQTEL LSPGSGRAEE EEDQDEGIKQ
   481  AMNHFVQENG TLRAKPTGNG IYINGRGHLV

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against NECTIN4 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

1

Mean surface accessibility (rSASA)

0.43

Highest tissue expression

110 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about NECTIN4.

Disease | AllUniProt

Conditions NECTIN4 is implicated in, by any mechanism.

• Ectodermal dysplasia-syndactyly syndrome 1 (EDSS1) MIM:613573

Disease | GeneticClinVar

12 pathogenic / likely-pathogenic of 93 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Ectodermal dysplasia-syndactyly syndrome 1

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

1.72

gnomAD pLI

0.04

DepMap mean gene effect

-0.08

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 9% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules
• homophilic cell adhesion via plasma membrane adhesion molecules
• negative regulation of natural killer cell mediated cytotoxicity

Molecular functions

• cell adhesion mediator activity
• identical protein binding
• receptor ligand activity
• virus receptor activity

Cellular components

• adherens junction
• extracellular exosome
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Immunoglobulin subtype 2
• Immunoglobulin domain subtype
• Immunoglobulin-like domain
• Immunoglobulin V-set domain
• CD80-like, immunoglobulin C2-set
• Immunoglobulin-like fold
• Nectin-3/4, second Ig domain
• Immunoglobulin-like domain superfamily
• Nectin and Nectin-like
• Immunoglobulin V-set domain
• CD80-like C2-set immunoglobulin domain
• Immunoglobulin domain

KeywordsUniProt

• Cell adhesion
• Cell junction
• Cell membrane
• Disulfide bond
• Ectodermal dysplasia
• Glycoprotein
• Host cell receptor for virus entry
• Host-virus interaction
• Immunoglobulin domain
• Membrane
• Receptor
• Repeat
• Secreted
• Signal
• Transmembrane
• Transmembrane helix

InteractionsUniProt · HPA

Protein binding partners of NECTIN4 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• AFDN
• TIGIT