CDH4

Protein identityUniProt · HPA

UniProt accession

P55283

Gene

CDH4

Ensembl

ENSG00000179242

Chromosome

20

Canonical length

916 aa

Protein class

Predicted membrane proteins

Subcellular location

Plasma membrane

OverviewNCBI Gene

This gene is a classical cadherin from the cadherin superfamily. The encoded protein is a calcium-dependent cell-cell adhesion glycoprotein comprised of five extracellular cadherin repeats, a transmembrane region and a highly conserved cytoplasmic tail. Based on studies in chicken and mouse, this cadherin is thought to play an important role during brain segmentation and neuronal outgrowth. In addition, a role in kidney and muscle development is indicated. Of particular interest are studies showing stable cis-heterodimers of cadherins 2 and 4 in cotransfected cell lines. Previously thought to interact in an exclusively homophilic manner, this is the first evidence of cadherin heterodimerization. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

Canonical amino-acid sequenceUniProt

916 residues, UniProt reviewed canonical sequence.

>P55283|CDH4
     1  MTAGAGVLLL LLSLSGALRA HNEDLTTRET CKAGFSEDDY TALISQNILE GEKLLQVKFS
    61  SCVGTKGTQY ETNSMDFKVG ADGTVFATRE LQVPSEQVAF TVTAWDSQTA EKWDAVVRLL
   121  VAQTSSPHSG HKPQKGKKVV ALDPSPPPKD TLLPWPQHQN ANGLRRRKRD WVIPPINVPE
   181  NSRGPFPQQL VRIRSDKDND IPIRYSITGV GADQPPMEVF SIDSMSGRMY VTRPMDREEH
   241  ASYHLRAHAV DMNGNKVENP IDLYIYVIDM NDNRPEFINQ VYNGSVDEGS KPGTYVMTVT
   301  ANDADDSTTA NGMVRYRIVT QTPQSPSQNM FTINSETGDI VTVAAGLDRE KVQQYTVIVQ
   361  ATDMEGNLNY GLSNTATAII TVTDVNDNPP EFTASTFAGE VPENRVETVV ANLTVMDRDQ
   421  PHSPNWNAVY RIISGDPSGH FSVRTDPVTN EGMVTVVKAV DYELNRAFML TVMVSNQAPL
   481  ASGIQMSFQS TAGVTISIMD INEAPYFPSN HKLIRLEEGV PPGTVLTTFS AVDPDRFMQQ
   541  AVRYSKLSDP ASWLHINATN GQITTAAVLD RESLYTKNNV YEATFLAADN GIPPASGTGT
   601  LQIYLIDIND NAPELLPKEA QICEKPNLNA INITAADADV DPNIGPYVFE LPFVPAAVRK
   661  NWTITRLNGD YAQLSLRILY LEAGMYDVPI IVTDSGNPPL SNTSIIKVKV CPCDDNGDCT
   721  TIGAVAAAGL GTGAIVAILI CILILLTMVL LFVMWMKRRE KERHTKQLLI DPEDDVRDNI
   781  LKYDEEGGGE EDQDYDLSQL QQPEAMGHVP SKAPGVRRVD ERPVGAEPQY PIRPMVPHPG
   841  DIGDFINEGL RAADNDPTAP PYDSLLVFDY EGSGSTAGSV SSLNSSSSGD QDYDYLNDWG
   901  PRFKKLADMY GGGEED

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against CDH4 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)

0.41

Highest tissue expression

13 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about CDH4.

Disease | GeneticClinVar

1 pathogenic / likely-pathogenic of 199 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Abnormal brain morphology

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)

0.36

gnomAD pLI

0.74

gnomAD missense Z

2.02

DepMap mean gene effect

0.03

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 4% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• adherens junction organization
• axon extension
• axon guidance
• calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules
• cell adhesion
• cell migration
• cell morphogenesis
• cell-cell adhesion mediated by cadherin
• cell-cell junction assembly
• heterophilic cell-cell adhesion via plasma membrane cell adhesion molecules
• homophilic cell adhesion via plasma membrane adhesion molecules
• positive regulation of axon extension

Molecular functions

• beta-catenin binding
• cadherin binding
• calcium ion binding

Cellular components

• adherens junction
• catenin complex
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Cadherin, Y-type LIR-motif
• Cadherin-like
• Cadherin prodomain
• Cadherin-like superfamily
• Cadherin conserved site
• Catenin binding domain superfamily
• Cadherin
• Cadherin domain
• Cadherin, Y-type LIR-motif
• Cadherin prodomain like

KeywordsUniProt

• Calcium
• Cell adhesion
• Cell membrane
• Cleavage on pair of basic residues
• Glycoprotein
• Membrane
• Metal-binding
• Repeat
• Signal
• Transmembrane
• Transmembrane helix