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P22223 (CADH3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 147. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cadherin-3
Alternative name(s):
Placental cadherin
Short name=P-cadherin
Gene names
Name:CDH3
Synonyms:CDHP
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length829 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Cadherins are calcium-dependent cell adhesion proteins. They preferentially interact with themselves in a homophilic manner in connecting cells; cadherins may thus contribute to the sorting of heterogeneous cell types.

Subunit structure

Interacts with CDCP1 and CTNNB1. Ref.7 Ref.9

Subcellular location

Cell membrane; Single-pass type I membrane protein.

Tissue specificity

Expressed in some normal epithelial tissues and in some carcinoma cell lines. Ref.6

Domain

Three calcium ions are usually bound at the interface of each cadherin domain and rigidify the connections, imparting a strong curvature to the full-length ectodomain By similarity.

Involvement in disease

Hypotrichosis congenital with juvenile macular dystrophy (HJMD) [MIM:601553]: A disorder characterized by congenital hypotrichosis, early hair loss, and severe degenerative changes of the retinal macula that culminate in blindness during the second to third decade of life.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.11

Ectodermal dysplasia, with ectrodactyly and macular dystrophy (EEM) [MIM:225280]: A form of ectodermal dysplasia, a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. It is an autosomal recessive condition characterized by features of ectodermal dysplasia such as sparse eyebrows and scalp hair, and selective tooth agenesis associated with macular dystrophy and ectrodactyly.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.12

Sequence similarities

Contains 5 cadherin domains.

Ontologies

Keywords
   Biological processCell adhesion
Sensory transduction
Vision
   Cellular componentCell membrane
Membrane
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDisease mutation
Ectodermal dysplasia
Hypotrichosis
   DomainRepeat
Signal
Transmembrane
Transmembrane helix
   LigandCalcium
Metal-binding
   PTMCleavage on pair of basic residues
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processadherens junction organization

Traceable author statement. Source: Reactome

canonical Wnt signaling pathway

Inferred from mutant phenotype PubMed 23334344. Source: UniProt

cell adhesion

Traceable author statement Ref.1. Source: ProtInc

cell junction assembly

Traceable author statement. Source: Reactome

cell-cell junction organization

Traceable author statement. Source: Reactome

hair cycle process

Inferred from mutant phenotype PubMed 23143461. Source: UniProt

homophilic cell adhesion

Inferred from electronic annotation. Source: InterPro

keratinization

Inferred from mutant phenotype PubMed 22696062. Source: UniProt

negative regulation of catagen

Inferred from mutant phenotype PubMed 22696062. Source: UniProt

negative regulation of transforming growth factor beta2 production

Inferred from mutant phenotype PubMed 22696062. Source: UniProt

positive regulation of gene expression

Inferred from mutant phenotype PubMed 23334344. Source: UniProt

positive regulation of insulin-like growth factor receptor signaling pathway

Inferred from mutant phenotype PubMed 22696062. Source: UniProt

positive regulation of keratinocyte proliferation

Inferred from mutant phenotype PubMed 22696062. Source: UniProt

positive regulation of melanin biosynthetic process

Inferred from mutant phenotype PubMed 23334344. Source: UniProt

positive regulation of melanosome transport

Inferred from mutant phenotype PubMed 23334344. Source: UniProt

positive regulation of monophenol monooxygenase activity

Inferred from mutant phenotype PubMed 23334344. Source: UniProt

regulation of hair cycle by canonical Wnt signaling pathway

Inferred from mutant phenotype PubMed 22696062. Source: UniProt

response to drug

Inferred from electronic annotation. Source: Ensembl

retina homeostasis

Inferred from mutant phenotype PubMed 23143461. Source: UniProt

single organismal cell-cell adhesion

Inferred from electronic annotation. Source: Ensembl

visual perception

Inferred from electronic annotation. Source: UniProtKB-KW

wound healing

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcell-cell adherens junction

Inferred from electronic annotation. Source: Ensembl

cytoplasm

Inferred from electronic annotation. Source: Ensembl

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

plasma membrane

Inferred from direct assay PubMed 10460003. Source: UniProtKB

   Molecular_functioncalcium ion binding

Inferred from electronic annotation. Source: InterPro

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P22223-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P22223-2)

The sequence of this isoform differs from the canonical sequence as follows:
     761-829: NLKAANTDPT...ADMYGGGEDD → GRGERGSQRGNGGLQLARGRTRRS
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2424 Potential
Propeptide25 – 10783
PRO_0000003745
Chain108 – 829722Cadherin-3
PRO_0000003746

Regions

Topological domain108 – 654547Extracellular Potential
Transmembrane655 – 67723Helical; Potential
Topological domain678 – 829152Cytoplasmic Potential
Domain108 – 215108Cadherin 1
Domain216 – 328113Cadherin 2
Domain329 – 440112Cadherin 3
Domain441 – 546106Cadherin 4
Domain547 – 650104Cadherin 5
Compositional bias785 – 80016Ser-rich

Amino acid modifications

Glycosylation2001N-linked (GlcNAc...) Potential
Glycosylation5661N-linked (GlcNAc...) Potential

Natural variations

Alternative sequence761 – 82969NLKAA…GGEDD → GRGERGSQRGNGGLQLARGR TRRS in isoform 2.
VSP_024820
Natural variant2371V → M. Ref.4
Corresponds to variant rs17854171 [ dbSNP | Ensembl ].
VAR_031929
Natural variant3221N → I in EEM. Ref.12
VAR_033010
Natural variant4771R → H.
Corresponds to variant rs34494880 [ dbSNP | Ensembl ].
VAR_031930
Natural variant5031R → H in HJMD. Ref.11
VAR_015422
Natural variant5631Q → H. Ref.1 Ref.2 Ref.3 Ref.12
Corresponds to variant rs1126933 [ dbSNP | Ensembl ].
VAR_031931

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 2007. Version 2.
Checksum: 7C03C8536CD98C7B

FASTA82991,418
        10         20         30         40         50         60 
MGLPRGPLAS LLLLQVCWLQ CAASEPCRAV FREAEVTLEA GGAEQEPGQA LGKVFMGCPG 

        70         80         90        100        110        120 
QEPALFSTDN DDFTVRNGET VQERRSLKER NPLKIFPSKR ILRRHKRDWV VAPISVPENG 

       130        140        150        160        170        180 
KGPFPQRLNQ LKSNKDRDTK IFYSITGPGA DSPPEGVFAV EKETGWLLLN KPLDREEIAK 

       190        200        210        220        230        240 
YELFGHAVSE NGASVEDPMN ISIIVTDQND HKPKFTQDTF RGSVLEGVLP GTSVMQVTAT 

       250        260        270        280        290        300 
DEDDAIYTYN GVVAYSIHSQ EPKDPHDLMF TIHRSTGTIS VISSGLDREK VPEYTLTIQA 

       310        320        330        340        350        360 
TDMDGDGSTT TAVAVVEILD ANDNAPMFDP QKYEAHVPEN AVGHEVQRLT VTDLDAPNSP 

       370        380        390        400        410        420 
AWRATYLIMG GDDGDHFTIT THPESNQGIL TTRKGLDFEA KNQHTLYVEV TNEAPFVLKL 

       430        440        450        460        470        480 
PTSTATIVVH VEDVNEAPVF VPPSKVVEVQ EGIPTGEPVC VYTAEDPDKE NQKISYRILR 

       490        500        510        520        530        540 
DPAGWLAMDP DSGQVTAVGT LDREDEQFVR NNIYEVMVLA MDNGSPPTTG TGTLLLTLID 

       550        560        570        580        590        600 
VNDHGPVPEP RQITICNQSP VRQVLNITDK DLSPHTSPFQ AQLTDDSDIY WTAEVNEEGD 

       610        620        630        640        650        660 
TVVLSLKKFL KQDTYDVHLS LSDHGNKEQL TVIRATVCDC HGHVETCPGP WKGGFILPVL 

       670        680        690        700        710        720 
GAVLALLFLL LVLLLLVRKK RKIKEPLLLP EDDTRDNVFY YGEEGGGEED QDYDITQLHR 

       730        740        750        760        770        780 
GLEARPEVVL RNDVAPTIIP TPMYRPRPAN PDEIGNFIIE NLKAANTDPT APPYDTLLVF 

       790        800        810        820 
DYEGSGSDAA SLSSLTSSAS DQDQDYDYLN EWGSRFKKLA DMYGGGEDD 

« Hide

Isoform 2 [UniParc].

Checksum: 0BE52C6E9C281154
Show »

FASTA78486,552

References

« Hide 'large scale' references
[1]"Molecular cloning of a human Ca2+-dependent cell-cell adhesion molecule homologous to mouse placental cadherin: its low expression in human placental tissues."
Shimoyama Y., Yoshida T., Terada M., Shimosato Y., Abe O., Hirohashi S.
J. Cell Biol. 109:1787-1794(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT HIS-563.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT HIS-563.
Tissue: Tongue.
[3]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT HIS-563.
[4]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2), VARIANT MET-237.
Tissue: Skin and Testis.
[5]"P-cadherin is a basal cell-specific epithelial marker that is not expressed in prostate cancer."
Jarrard D.F., Paul R., Van Bokhoven A., Nguyen S.H., Bova G.S., Wheelock M.J., Johnson K.R., Schalken J., Bussemakers M., Isaacs W.B.
Clin. Cancer Res. 3:2121-2128(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-15.
Tissue: Fetal brain.
[6]"Cadherin cell-adhesion molecules in human epithelial tissues and carcinomas."
Shimoyama Y., Hirohashi S., Hirano S., Noguchi M., Shimosato Y., Takeichi M., Abe O.
Cancer Res. 49:2128-2133(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[7]"Adhesion signaling by a novel mitotic substrate of src kinases."
Bhatt A.S., Erdjument-Bromage H., Tempst P., Craik C.S., Moasser M.M.
Oncogene 24:5333-5343(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CDCP1.
[8]"Hypotrichosis with juvenile macular dystrophy is caused by a mutation in CDH3, encoding P-cadherin."
Sprecher E., Bergman R., Richard G., Lurie R., Shalev S., Petronius D., Shalata A., Anbinder Y., Leibu R., Perlman I., Cohen N., Szargel R.
Nat. Genet. 29:134-136(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN HJMD.
[9]"Crystal structure of a beta-catenin/BCL9/Tcf4 complex."
Sampietro J., Dahlberg C.L., Cho U.S., Hinds T.R., Kimelman D., Xu W.
Mol. Cell 24:293-300(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CTNNB1.
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"A missense mutation in CDH3, encoding P-cadherin, causes hypotrichosis with juvenile macular dystrophy."
Indelman M., Bergman R., Lurie R., Richard G., Miller B., Petronius D., Ciubutaro D., Leibu R., Sprecher E.
J. Invest. Dermatol. 119:1210-1213(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT HJMD HIS-503.
[12]"Distinct CDH3 mutations cause ectodermal dysplasia, ectrodactyly, macular dystrophy (EEM syndrome)."
Kjaer K.W., Hansen L., Schwabe G.C., Marques-de-Faria A.P., Eiberg H., Mundlos S., Tommerup N., Rosenberg T.
J. Med. Genet. 42:292-298(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT EEM ILE-322, VARIANT HIS-563.
+Additional computationally mapped references.

Web resources

Mutations of the CDH3 gene

Retina International's Scientific Newsletter

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X63629 mRNA. Translation: CAA45177.1.
AK312554 mRNA. Translation: BAG35451.1.
CH471092 Genomic DNA. Translation: EAW83238.1.
BC014462 mRNA. Translation: AAH14462.1.
BC041846 mRNA. Translation: AAH41846.1.
X95824 Genomic DNA. Translation: CAA65093.1.
CCDSCCDS10868.1. [P22223-1]
PIRIJHUCP. A33659.
RefSeqNP_001784.2. NM_001793.4. [P22223-1]
UniGeneHs.191842.

3D structure databases

ProteinModelPortalP22223.
SMRP22223. Positions 108-647, 729-822.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107436. 7 interactions.
IntActP22223. 5 interactions.
STRING9606.ENSP00000264012.

PTM databases

PhosphoSiteP22223.

Polymorphism databases

DMDM146345382.

Proteomic databases

MaxQBP22223.
PaxDbP22223.
PRIDEP22223.

Protocols and materials databases

DNASU1001.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264012; ENSP00000264012; ENSG00000062038. [P22223-1]
ENST00000429102; ENSP00000398485; ENSG00000062038. [P22223-2]
GeneID1001.
KEGGhsa:1001.
UCSCuc002ewf.2. human. [P22223-1]

Organism-specific databases

CTD1001.
GeneCardsGC16P068679.
H-InvDBHIX0026973.
HGNCHGNC:1762. CDH3.
HPACAB002487.
HPA001767.
MIM114021. gene.
225280. phenotype.
601553. phenotype.
neXtProtNX_P22223.
Orphanet1897. EEM syndrome.
1573. Hypotrichosis with juvenile macular degeneration.
PharmGKBPA26299.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG328838.
HOGENOMHOG000231254.
HOVERGENHBG106438.
InParanoidP22223.
KOK06796.
OMAKQDTYDV.
OrthoDBEOG7PS1DS.
PhylomeDBP22223.
TreeFamTF316817.

Enzyme and pathway databases

ReactomeREACT_111155. Cell-Cell communication.

Gene expression databases

ArrayExpressP22223.
BgeeP22223.
CleanExHS_CDH3.
GenevestigatorP22223.

Family and domain databases

Gene3D2.60.40.60. 5 hits.
4.10.900.10. 1 hit.
InterProIPR002126. Cadherin.
IPR015919. Cadherin-like.
IPR020894. Cadherin_CS.
IPR000233. Cadherin_cytoplasmic-dom.
IPR027397. Catenin_binding_dom.
[Graphical view]
PfamPF00028. Cadherin. 4 hits.
PF01049. Cadherin_C. 1 hit.
[Graphical view]
PRINTSPR00205. CADHERIN.
SMARTSM00112. CA. 4 hits.
[Graphical view]
SUPFAMSSF49313. SSF49313. 5 hits.
PROSITEPS00232. CADHERIN_1. 3 hits.
PS50268. CADHERIN_2. 5 hits.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSCDH3. human.
GeneWikiCDH3_(gene).
GenomeRNAi1001.
NextBio4208.
PROP22223.
SOURCESearch...

Entry information

Entry nameCADH3_HUMAN
AccessionPrimary (citable) accession number: P22223
Secondary accession number(s): B2R6F4, Q05DI6
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1991
Last sequence update: May 1, 2007
Last modified: July 9, 2014
This is version 147 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 16

Human chromosome 16: entries, gene names and cross-references to MIM