P22223 (CADH3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cadherin-3

Alternative name(s):
Placental cadherin
Short name=P-cadherin

Gene names

Name:	CDH3
Synonyms:	CDHP

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	829 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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. Ref.7
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
Involvement in disease	Defects in CDH3 are the cause of hypotrichosis with juvenile macular dystrophy (HJMD) [MIM:601553]. HJMD is a rare autosomal recessive disorder characterized by early hair loss heralding severe degenerative changes of the retinal macula and culminating in blindness during the second to third decade of life. Ref.8 Ref.10 Defects in CDH3 are the cause of ectodermal dysplasia with ectrodactyly and macular dystrophy (EEM) [MIM:225280]; also known as EEM syndrome, Albrectsen-Svendsen syndrome or Ohdo-Hirayama-Terawaki syndrome. Ectodermal dysplasia defines a heterogeneous group of disorders due to abnormal development of two or more ectodermal structures. EEM 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. Ref.11
Sequence similarities	Contains 5 cadherin domains.

Ontologies

Keywords
Biological process	Cell adhesion Sensory transduction Vision
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Ectodermal dysplasia Hypotrichosis
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	Calcium
PTM	Cleavage on pair of basic residues Glycoprotein Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	adherens junction organization Traceable author statement. Source: Reactome cell junction assembly Traceable author statement. Source: Reactome homophilic cell adhesion Inferred from electronic annotation. Source: InterPro response to stimulus Inferred from electronic annotation. Source: UniProtKB-KW visual perception Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW plasma membrane Inferred from direct assay. Source: UniProtKB
Molecular function	calcium 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 24	24	Potential
	Propeptide	25 – 107	83			PRO_0000003745
	Chain	108 – 829	722	Cadherin-3		PRO_0000003746
Regions
	Topological domain	108 – 654	547	Extracellular Potential
	Transmembrane	655 – 677	23	Helical; Potential
	Topological domain	678 – 829	152	Cytoplasmic Potential
	Domain	108 – 215	108	Cadherin 1
	Domain	216 – 328	113	Cadherin 2
	Domain	329 – 440	112	Cadherin 3
	Domain	441 – 546	106	Cadherin 4
	Domain	547 – 650	104	Cadherin 5
	Compositional bias	785 – 800	16	Ser-rich
Amino acid modifications
	Modified residue	713	1	Phosphotyrosine Ref.9
	Glycosylation	200	1	N-linked (GlcNAc...) Potential
	Glycosylation	566	1	N-linked (GlcNAc...) Potential
Natural variations
	Alternative sequence	761 – 829	69	NLKAA…GGEDD → GRGERGSQRGNGGLQLARGR TRRS in isoform 2.		VSP_024820
	Natural variant	237	1	V → M. Ref.4 Corresponds to variant rs17854171 [ dbSNP | Ensembl ].		VAR_031929
	Natural variant	322	1	N → I in EEM. Ref.11		VAR_033010
	Natural variant	477	1	R → H. Corresponds to variant rs34494880 [ dbSNP | Ensembl ].		VAR_031930
	Natural variant	503	1	R → H in HJMD. Ref.10		VAR_015422
	Natural variant	563	1	Q → H. Ref.1 Ref.2 Ref.3 Ref.11 Corresponds to variant rs1126933 [ dbSNP | Ensembl ].		VAR_031931

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified May 1, 2007. Version 2. Checksum: 7C03C8536CD98C7B	FASTA	829	91,418
	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
	Isoform 2 [UniParc]. Checksum: 0BE52C6E9C281154	FASTA	784	86,552
	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 GRGERGSQRG NGGLQLARGR TRRS

References

	« Hide 'large scale' referencesShow '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: 2793940] [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. , 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: 14702039] [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. , 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: 15489334] [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: 9815605] [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: 2702654] [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: 16007225] [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: 11544476] [Abstract] Cited for: INVOLVEMENT IN HJMD.
[9]	"An extensive survey of tyrosine phosphorylation revealing new sites in human mammary epithelial cells." Heibeck T.H., Ding S.-J., Opresko L.K., Zhao R., Schepmoes A.A., Yang F., Tolmachev A.V., Monroe M.E., Camp D.G. II, Smith R.D., Wiley H.S., Qian W.-J. J. Proteome Res. 8:3852-3861(2009) [PubMed: 19534553] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-713, MASS SPECTROMETRY. Tissue: Mammary epithelium.
[10]	"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: 12445216] [Abstract] Cited for: VARIANT HJMD HIS-503.
[11]	"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: 15805154] [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

GeneReviews

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.
IPI	IPI00645614. IPI00747243.
PIR	IJHUCP. A33659.
RefSeq	NP_001784.2. NM_001793.4.
UniGene	Hs.191842.
3D structure databases
ProteinModelPortal	P22223.
SMR	P22223. Positions 20-97, 108-648, 729-822.
ModBase	Search...
Protein-protein interaction databases
IntAct	P22223. 4 interactions.
STRING	P22223.
PTM databases
PhosphoSite	P22223.
Polymorphism databases
DMDM	146345382.
Proteomic databases
PRIDE	P22223.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264012; ENSP00000264012; ENSG00000062038.
GeneID	1001.
KEGG	hsa:1001.
NMPDR	fig|9606.3.peg.12459.
UCSC	uc002ewf.2. human.
Organism-specific databases
CTD	1001.
GeneCards	GC16P068679.
H-InvDB	HIX0026973.
HGNC	HGNC:1762. CDH3.
HPA	CAB002487. HPA001767.
MIM	114021. gene. 225280. phenotype. 601553. phenotype.
neXtProt	NX_P22223.
Orphanet	1897. EEM syndrome. 1573. Juvenile macular degeneration - hypotrichosis.
PharmGKB	PA26299.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG11213.
GeneTree	ENSGT00550000074431.
HOGENOM	HBG505775.
HOVERGEN	HBG106438.
InParanoid	P22223.
OMA	CTYTAQD.
OrthoDB	EOG4GF3DT.
PhylomeDB	P22223.
Enzyme and pathway databases
Reactome	REACT_111155. Cell-Cell communication.
Gene expression databases
ArrayExpress	P22223.
Bgee	P22223.
CleanEx	HS_CDH3.
Genevestigator	P22223.
GermOnline	ENSG00000062038. Homo sapiens.
Family and domain databases
InterPro	IPR002126. Cadherin. IPR015919. Cadherin-like. IPR020894. Cadherin_CS. IPR000233. Cadherin_cytoplasmic-dom. [Graphical view]
Gene3D	G3DSA:2.60.40.60. Cadherin. 4 hits.
KO	K06796.
Pfam	PF00028. Cadherin. 4 hits. PF01049. Cadherin_C. 1 hit. [Graphical view]
PRINTS	PR00205. CADHERIN.
SMART	SM00112. CA. 4 hits. [Graphical view]
SUPFAM	SSF49313. Cadherin. 5 hits.
PROSITE	PS00232. CADHERIN_1. 3 hits. PS50268. CADHERIN_2. 5 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	4208.
SOURCE	Search...

Entry information

Entry name

CADH3_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 120 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.