Reviewed, UniProtKB/Swiss-Prot P12830 (CADH1_HUMAN)

Names and origin

Protein names

Recommended name:
    Cadherin-1
Alternative name(s):
    Epithelial cadherin
      Short name=E-cadherin
    Uvomorulin
    CAM 120/80
    CD_antigen=CD324
Cleaved into the following 3 chains:
    1- Recommended name:
            E-Cad/CTF1
    2- Recommended name:
            E-Cad/CTF2
    3- Recommended name:
            E-Cad/CTF3

Gene names

Name:	CDH1
Synonyms:	CDHE, UVO

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	882 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. CDH1 is involved in mechanisms regulating cell-cell adhesions, mobility and proliferation of epithelial cells. Has a potent invasive suppressor role. It is a ligand for integrin alpha-E/beta-7. Ref.21 E-Cad/CTF2 promotes non-amyloidogenic degradation of Abeta precursors. Has a strong inhibitory effect on APP C99 and C83 production. Ref.21
Subunit structure	Homodimer; disulfide-linked. Interacts directly, via the cytoplasmic domain, with CTNNB1 or JUP to form the PSEN1/cadherin/catenin adhesion complex which connects to the actin skeleton through the actin binding of alpha-catenin. Interaction with PSEN1, cleaves CDH1 resulting in the disassociation of cadherin-based adherens junctions (CAJs). Interacts with AJAP1, CTNND1 and DLGAP5. Ref.16 Ref.17 Ref.18 Ref.19
Subcellular location	Cell junction. Cell membrane; Single-pass type I membrane protein. Note: Colocalizes with DLGAP5 at sites of cell-cell contact in intestinal epithelial cells. Anchored to actin microfilaments through association with alpha-, beta- and gamma-catenin. Sequential proteolysis induced by apoptosis or calcium influx, results in translocation from sites of cell-cell contact to the cytoplasm. Ref.18 Ref.4
Tissue specificity	Non-neural epithelial tissues.
Post-translational modification	During apoptosis or with calcium influx, cleaved by a membrane-bound metalloproteinase (ADAM10), PS1/gamma-secretase and caspase-3 to produce fragments of about 38 kDa (E-CAD/CTF1), 33 kDa (E-CAD/CTF2) and 29 kDa (E-CAD/CTF3), respectively. Processing by the metalloproteinase, induced by calcium influx, causes disruption of cell-cell adhesion and the subsequent release of beta-catenin into the cytoplasm. The residual membrane-tethered cleavage product is rapidly degraded via an intracellular proteolytic pathway. Cleavage by caspase-3 releases the cytoplasmic tail resulting in disintegration of the actin microfilament system. The gamma-secretase-mediated cleavage promotes disaaaembly of adherens junctions. Ref.4 Ref.12 Ref.15
Involvement in disease	Defects in CDH1 are involved in dysfunction of the cell-cell adhesion system, triggering cancer invasion (gastric, breast, ovary, endometrium and thyroid) and metastasis. Defects in CDH1 are a cause of gastric cancer [MIM:137215]; also known as hereditary familial diffuse gastric cancer (HDGC). Defects in CDH1 are a cause of susceptibility to endometrial cancer [MIM:608089]. Defects in CDH1 are associated with ovarian cancer [MIM:167000]. Ovarian cancer is the leading cause of death from gynecologic malignancy. It is characterized by advanced presentation with loco-regional dissemination in the peritoneal cavity and the rare incidence of visceral metastases. These typical features relate to the biology of the disease, which is a principal determinant of outcome.
Sequence similarities	Contains 5 cadherin domains.
Sequence caution	The sequence AAA61259.1 differs from that shown. Reason: Frameshift at positions 16, 22, 25, 28, 31, 34, 52, 67, 73, 76, 94, 102, 633 and 636.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell junction Cell membrane Membrane
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Repeat Signal Transmembrane
Ligand	Calcium
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	homophilic cell adhesion Ref.11 Non-traceable author statement. Source: UniProtKB positive regulation of transcription factor import into nucleus Inferred from direct assay. Source: UniProtKB
Cellular component	Golgi apparatus Inferred from direct assay. Source: HPA actin cytoskeleton Inferred from direct assay. Source: UniProtKB catenin complex Inferred from direct assay. Source: UniProtKB cell-cell adherens junction Inferred from direct assay. Source: UniProtKB focal adhesion Inferred from direct assay. Source: HPA integral to membrane Inferred from direct assay. Source: UniProtKB lateral plasma membrane Inferred from direct assay. Source: UniProtKB perinuclear region of cytoplasm Inferred from direct assay. Source: UniProtKB
Molecular function	calcium ion binding Inferred from electronic annotation. Source: UniProtKB-KW cell adhesion molecule binding Non-traceable author statement. Source: UniProtKB transcription activator activity Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CTNNB1	P35222	1	EBI-727477,EBI-491549
FGFR1	P11362	1	EBI-727477,EBI-1028277
inlA	P25146	1	EBI-727477,EBI-1035388	From a different organism.
PPP1CA	P62136	2	EBI-727477,EBI-357253
PRKD1	Q15139	3	EBI-727477,EBI-1181072

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 22

22

Potential

Propeptide

23 – 154

132

Potential

PRO_0000003715

Chain

155 – 882

728

Cadherin-1

PRO_0000003716

Chain

701 – 882

182

E-Cad/CTF1

PRO_0000236067

Chain

732 – 882

151

E-Cad/CTF2

PRO_0000236068

Chain

751 – 882

132

E-Cad/CTF3

PRO_0000236069

Regions

Topological domain

155 – 709

555

Extracellular Potential

Transmembrane

710 – 730

21

Potential

Topological domain

731 – 882

152

Cytoplasmic Potential

Domain

155 – 262

108

Cadherin 1

Domain

263 – 375

113

Cadherin 2

Domain

376 – 486

111

Cadherin 3

Domain

487 – 593

107

Cadherin 4

Domain

594 – 697

104

Cadherin 5

Region

758 – 769

12

Required for binding CTNND1 and PSEN1

Region

811 – 882

72

Required for binding alpha, beta and gamma catenins

Compositional bias

838 – 851

14

Ser-rich

Sites

Site

700 – 701

2

Cleavage; by a metalloproteinase

Site

731 – 732

2

Cleavage; by gamma-secretase/PS1

Site

750 – 751

2

Cleavage; by caspase-3

Amino acid modifications

Modified residue

838

1

Phosphoserine By similarity

Modified residue

840

1

Phosphoserine By similarity

Modified residue

846

1

Phosphoserine By similarity

Glycosylation

558

1

N-linked (GlcNAc...) Potential

Glycosylation

637

1

N-linked (GlcNAc...) Potential

Disulfide bond

163

Interchain Ref.17

Natural variations

Natural variant

72

1

D → N: dbSNP rs35606263.

VAR_048500

Natural variant

123

1

H → Y in diffuse gastric cancer.

VAR_001306

Natural variant

193

1

T → P in diffuse gastric cancer. Ref.26

VAR_001307

Natural variant

244

1

D → G in HDGC. Ref.30

VAR_008712

Natural variant

270

1

S → A May contribute to prostate cancer. Ref.32

VAR_013970

Natural variant

274 – 277

4

Missing in gastric adenocarcinoma. Ref.2

VAR_001308

Natural variant

282

1

M → I in a breast cancer sample; somatic mutation. Ref.37

VAR_033026

Natural variant

315

1

N → S in lobular breast carcinoma. Ref.24

VAR_001309

Natural variant

336

1

E → D Ref.29

VAR_001310

Natural variant

340

1

T → A in HDGC and colorectal cancer; cells exhibited decreased aggregation increased invasiveness and non-uniform migration in vitro compared to cells transfected with wild-type sequence.

VAR_013971

Natural variant

370

1

D → A in diffuse gastric cancer. Ref.11

VAR_001311

Natural variant

393

1

I → N: dbSNP rs34466743.

VAR_048501

Natural variant

400

1

Missing in gastric carcinoma; loss of heterozygosity. Ref.27

VAR_001312

Natural variant

418 – 423

6

Missing in gastric carcinoma. Ref.27

VAR_001313

Natural variant

463

1

E → Q in diffuse gastric cancer.

VAR_001314

Natural variant

470

1

T → I Ref.29

VAR_001315

Natural variant

473

1

V → D in diffuse gastric cancer. Ref.11

VAR_001317

Natural variant

473

1

V → I: dbSNP rs36087757. Ref.11

VAR_048502

Natural variant

478

1

L → P: dbSNP rs35520415.

VAR_023357

Natural variant

487

1

V → A in HDGC. Ref.30

VAR_008713

Natural variant

592

1

A → T in thyroid cancer; may play a role in colorectal carcinogenesis. dbSNP rs35187787. Ref.28 Ref.33

VAR_001318

Natural variant

598

1

R → Q in diffuse gastric cancer.

VAR_001319

Natural variant

617

1

A → T in endometrial cancer; loss of heterozygosity; also found as a polymorphism; cells exhibited an intermediate phenotype concerning aggregation invasiveness and migration in vitro compared to cells transfected with wild-type sequence. dbSNP rs33935154. Ref.5 Ref.25

VAR_001320

Natural variant

630

1

L → V: dbSNP rs2276331.

VAR_021868

Natural variant

634

1

A → V in gastric cancer; cells exhibited decreased aggregation increased invasiveness and non-uniform migration in vitro compared to cells transfected with wild-type sequence.

VAR_055431

Natural variant

695

1

C → R: dbSNP rs9282655.

VAR_021869

Natural variant

711

1

L → V in endometrial cancer. Ref.25

VAR_001321

Natural variant

777

1

D → N in a breast cancer sample; somatic mutation. Ref.37

VAR_033027

Natural variant

832

1

V → M in HDGC. dbSNP rs35572355.

VAR_023358

Natural variant

838

1

S → G in ovarian cancer; somatic mutation; loss of heterozygosity.

VAR_001322

Natural variant

880

1

E → K: dbSNP rs34507583.

VAR_023359

Experimental info

Mutagenesis

759 – 761

3

GGG → AAA: Binds to CTNNB1 but abolishes formation of the PSEN1/CTNNB1 complex; when associated with CTNNB1 D-431. Abolishes binding PSEN1. Abolishes gamma-secretase cleavage. Ref.12 Ref.20

Sequence conflict

10

1

A → G in AAA61259. Ref.3

Sequence conflict

29

1

H → L in AAA61259. Ref.3

Sequence conflict

47

1

E → R in AAA61259. Ref.3

Sequence conflict

70 – 71

2

SL → P in AAA61259. Ref.3

Sequence conflict

483

1

A → G in AAA61259. Ref.3

Sequence conflict

530

1

A → R in AAA61259. Ref.3

Sequence conflict

543

1

S → F in CAA79356. Ref.2

Sequence conflict

615

1

I → H in AAA61259. Ref.3

Sequence conflict

634 – 636

3

ASA → RVP in AAA61259. Ref.3

Sequence conflict

868

1

R → P in AAA61259. Ref.3

Sequence conflict

882

1

D → H in AAA61259. Ref.3

Secondary structure

1

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882

Helix Strand Turn

Details...

Beta strand

161 – 164

4

Beta strand

169 – 177

9

Helix

181 – 184

4

Beta strand

188 – 195

8

Turn

196 – 198

3

Beta strand

199 – 201

3

Beta strand

204 – 207

4

Turn

209 – 211

3

Beta strand

213 – 216

4

Turn

222 – 224

3

Beta strand

227 – 236

10

Beta strand

241 – 243

3

Beta strand

246 – 253

8

Beta strand

261 – 272

12

Beta strand

280 – 283

4

Turn

292 – 294

3

Beta strand

301 – 309

9

Beta strand

316 – 319

4

Turn

321 – 323

3

Beta strand

325 – 328

4

Turn

335 – 337

3

Beta strand

340 – 348

9

Turn

349 – 353

5

Beta strand

356 – 366

11

Sequences

	Sequence		Length	Mass (Da)
	P12830-1 [UniParc]. Last modified July 1, 1993. Version 3. Checksum: E427118043A13C67	FASTA	882	97,456
	10 20 30 40 50 60 MGPWSRSLSA LLLLLQVSSW LCQEPEPCHP GFDAESYTFT VPRRHLERGR VLGRVNFEDC 70 80 90 100 110 120 TGRQRTAYFS LDTRFKVGTD GVITVKRPLR FHNPQIHFLV YAWDSTYRKF STKVTLNTVG 130 140 150 160 170 180 HHHRPPPHQA SVSGIQAELL TFPNSSPGLR RQKRDWVIPP ISCPENEKGP FPKNLVQIKS 190 200 210 220 230 240 NKDKEGKVFY SITGQGADTP PVGVFIIERE TGWLKVTEPL DRERIATYTL FSHAVSSNGN 250 260 270 280 290 300 AVEDPMEILI TVTDQNDNKP EFTQEVFKGS VMEGALPGTS VMEVTATDAD DDVNTYNAAI 310 320 330 340 350 360 AYTILSQDPE LPDKNMFTIN RNTGVISVVT TGLDRESFPT YTLVVQAADL QGEGLSTTAT 370 380 390 400 410 420 AVITVTDTND NPPIFNPTTY KGQVPENEAN VVITTLKVTD ADAPNTPAWE AVYTILNDDG 430 440 450 460 470 480 GQFVVTTNPV NNDGILKTAK GLDFEAKQQY ILHVAVTNVV PFEVSLTTST ATVTVDVLDV 490 500 510 520 530 540 NEAPIFVPPE KRVEVSEDFG VGQEITSYTA QEPDTFMEQK ITYRIWRDTA NWLEINPDTG 550 560 570 580 590 600 AISTRAELDR EDFEHVKNST YTALIIATDN GSPVATGTGT LLLILSDVND NAPIPEPRTI 610 620 630 640 650 660 FFCERNPKPQ VINIIDADLP PNTSPFTAEL THGASANWTI QYNDPTQESI ILKPKMALEV 670 680 690 700 710 720 GDYKINLKLM DNQNKDQVTT LEVSVCDCEG AAGVCRKAQP VEAGLQIPAI LGILGGILAL 730 740 750 760 770 780 LILILLLLLF LRRRAVVKEP LLPPEDDTRD NVYYYDEEGG GEEDQDFDLS QLHRGLDARP 790 800 810 820 830 840 EVTRNDVAPT LMSVPRYLPR PANPDEIGNF IDENLKAADT DPTAPPYDSL LVFDYEGSGS 850 860 870 880 EAASLSSLNS SESDKDQDYD YLNEWGNRFK KLADMYGGGE DD

References

[1]	"Molecular cloning and characterization of the human E-cadherin cDNA." Bussemakers M.J.G., Mees S.G.M., van Bokhoven A., Debruyne F.M.J., Schalken J.A. Mol. Biol. Rep. 17:123-128(1993) [PubMed: 8459805] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Pancreas.
[2]	"E-cadherin gene mutations in human gastric carcinoma cell lines." Oda T., Kanai Y., Oyama T., Yoshiura K., Shimoyama Y., Birchmeier W., Sugimura T., Hirohashi S. Proc. Natl. Acad. Sci. U.S.A. 91:1858-1862(1994) [PubMed: 8127895] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT GASTRIC ADENOCARCINOMA 274-GLY--PRO-277 DEL.
[3]	"Molecular cloning of human E-cadherin suggests a novel subdivision of the cadherin superfamily." Rimm D.L., Morrow J.S. Biochem. Biophys. Res. Commun. 200:1754-1761(1994) [PubMed: 8185635] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[4]	"Calcium influx triggers the sequential proteolysis of extracellular and cytoplasmic domains of E-cadherin, leading to loss of beta-catenin from cell-cell contacts." Ito K., Okamoto I., Araki N., Kawano Y., Nakao M., Fujiyama S., Tomita K., Mimori T., Saya H. Oncogene 18:7080-7090(1999) [PubMed: 10597309] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 586-591, PROTEOLYTIC PROCESSING, SUBCELLULAR LOCATION. Tissue: Epidermal carcinoma.
[5]	NIEHS SNPs program Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS PRO-478; THR-617; MET-832 AND LYS-880.
[6]	"Transcriptional regulation of the human E-cadherin gene in human prostate cancer cell lines: characterization of the human E-cadherin gene promoter." Bussemakers M.J.G., Giroldi L.A., van Bokhoven A., Schalken J.A. Biochem. Biophys. Res. Commun. 203:1284-1290(1994) [PubMed: 8093045] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-16.
[7]	"Silencing of the E-cadherin invasion-suppressor gene by CpG methylation in human carcinomas." Yoshiura K., Kanai Y., Ochiai A., Shimoyama Y., Sugimura T., Hirohashi S. Proc. Natl. Acad. Sci. U.S.A. 92:7416-7419(1995) [PubMed: 7543680] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-16. Tissue: Placenta.
[8]	"Cloning and characterization of the human invasion suppressor gene E-cadherin (CDH1)." Berx G., Staes K., van Hengel J., Molemans F., Bussemakers M.J.G., van Bokhoven A., van Roy F. Genomics 26:281-289(1995) [PubMed: 7601454] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 56-882. Tissue: Placenta.
[9]	"Characterization and chromosomal localization of the gene encoding the human cell adhesion molecule uvomorulin." Mansouri A., Spurr N., Goodfellow P.N., Kemler R. Differentiation 38:67-71(1988) [PubMed: 3263290] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 172-311. Tissue: Liver.
[10]	Frixen U.H. Submitted (MAR-1990) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 265-392. Tissue: Liver.
[11]	"E-cadherin gene mutations provide clues to diffuse type gastric carcinomas." Becker K.-F., Atkinson M.J., Reich U., Becker I., Nekarda H., Siewert J.R., Hoefler H. Cancer Res. 54:3845-3852(1994) [PubMed: 8033105] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 337-476, VARIANTS DIFFUSE GASTRIC CANCER ALA-370 AND ASP-473.
[12]	"A presenilin-1/gamma-secretase cleavage releases the E-cadherin intracellular domain and regulates disassembly of adherens junctions." Marambaud P., Shioi J., Serban G., Georgakopoulos A., Sarner S., Nagy V., Baki L., Wen P., Efthimiopoulos S., Shao Z., Wisniewski T., Robakis N.K. EMBO J. 21:1948-1956(2002) [PubMed: 11953314] [Abstract] Cited for: PROTEIN SEQUENCE OF 701-714 AND 732-742, PROTEOLYTIC PROCESSING BY GAMMA-SECRETASE/PS1 AND A MEMBRANE-BOUND METALLOPROTEINASE, MUTAGENESIS OF 759-GLY--GLY-761.
[13]	"Uvomorulin-catenin complex formation is regulated by a specific domain in the cytoplasmic region of the cell adhesion molecule." Ozawa M., Ringwald M., Kemler R. Proc. Natl. Acad. Sci. U.S.A. 87:4246-4250(1990) [PubMed: 2349235] [Abstract] Cited for: DOMAIN CATENIN BINDING.
[14]	"Presenilin-1 forms complexes with the cadherin/catenin cell-cell adhesion system and is recruited to intercellular and synaptic contacts." Georgakopoulos A., Marambaud P., Efthimiopoulos S., Shioi J., Cui W., Li H.-C., Schutte M., Gordon R., Holstein G.R., Martinelli G., Mehta P., Friedrich V.L. Jr., Robakis N.K. Mol. Cell 4:893-902(1999) [PubMed: 10635315] [Abstract] Cited for: COMPONENT OF THE PSEN1/E-CADHERIN/CATENIN ADHESION COMPLEX WITH PSEN1; CDH1; CTNNA1 AND CTNNB1/CTNND1.
[15]	"Cleavage and shedding of E-cadherin after induction of apoptosis." Steinhusen U., Weiske J., Badock V., Tauber R., Bommert K., Huber O. J. Biol. Chem. 276:4972-4980(2001) [PubMed: 11076937] [Abstract] Cited for: PROTEOLYTIC PROCESSING.
[16]	"Presenilin-1 binds cytoplasmic epithelial cadherin, inhibits cadherin/p120 association, and regulates stability and function of the cadherin/catenin adhesion complex." Baki L., Marambaud P., Efthimiopoulos S., Georgakopoulos A., Wen P., Cui W., Shioi J., Koo E., Ozawa M., Friedrich V.L., Robakis N.K. Proc. Natl. Acad. Sci. U.S.A. 98:2381-2386(2001) [PubMed: 11226248] [Abstract] Cited for: INTERACTION WITH PSEN1.
[17]	"Disulfide bond formation promotes the cis- and trans-dimerization of the E-cadherin-derived first repeat." Makagiansar I.T., Nguyen P.D., Ikesue A., Kuczera K., Dentler W., Urbauer J.L., Galeva N., Alterman M., Siahaan T.J. J. Biol. Chem. 277:16002-16010(2002) [PubMed: 11856755] [Abstract] Cited for: INTERCHAIN DISULFIDE BOND.
[18]	"Human homolog of disc-large is required for adherens junction assembly and differentiation of human intestinal epithelial cells." Laprise P., Viel A., Rivard N. J. Biol. Chem. 279:10157-10166(2004) [PubMed: 14699157] [Abstract] Cited for: INTERACTION WITH DLGAP5, SUBCELLULAR LOCATION.
[19]	"Novel membrane protein shrew-1 targets to cadherin-mediated junctions in polarized epithelial cells." Bharti S., Handrow-Metzmacher H., Zickenheiner S., Zeitvogel A., Baumann R., Starzinski-Powitz A. Mol. Biol. Cell 15:397-406(2004) [PubMed: 14595118] [Abstract] Cited for: INTERACTION WITH AJAP1. Tissue: Brain.
[20]	"Cadherins mediate both the association between PS1 and beta-catenin and the effects of PS1 on beta-catenin stability." Serban G., Kouchi Z., Baki L., Georgakopoulos A., Litterst C.M., Shioi J., Robakis N.K. J. Biol. Chem. 280:36007-36012(2005) [PubMed: 16126725] [Abstract] Cited for: COMPONENT OF PSEN1/CATENIN/CADHERIN COMPLEX WITH PSEN1; CDH1 AND CTNNB1, MUTAGENESIS OF 759-GLY--GLY-761.
[21]	"The cytoplasmic sequence of E-cadherin promotes non-amyloidogenic degradation of A beta precursors." Agiostratidou G., Muros R.M., Shioi J., Marambaud P., Robakis N.K. J. Neurochem. 96:1182-1188(2006) [PubMed: 16417575] [Abstract] Cited for: FUNCTION OF E-CAD/CTF2.
[22]	"Structure of internalin, a major invasion protein of Listeria monocytogenes, in complex with its human receptor E-cadherin." Schubert W.-D., Urbanke C., Ziehm T., Beier V., Machner M.P., Domann E., Wehland J., Chakraborty T., Heinz D.W. Cell 111:825-836(2002) [PubMed: 12526809] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 156-255 IN COMPLEX WITH LISTERIA INTERNALIN.
[23]	"Mutations of the human E-cadherin (CDH1) gene." Berx G., Becker K.-F., Hoefler H., van Roy F. Hum. Mutat. 12:226-237(1998) [PubMed: 9744472] [Abstract] Cited for: REVIEW ON VARIANTS.
[24]	"Point mutation of the E-cadherin gene in invasive lobular carcinoma of the breast." Kanai Y., Oda T., Tsuda H., Ochiai A., Hirohashi S. Jpn. J. Cancer Res. 85:1035-1039(1994) [PubMed: 7961105] [Abstract] Cited for: VARIANT LOBULAR BREAST CARCINOMA SER-315.
[25]	"Mutations of the E-cadherin gene in human gynecologic cancers." Risinger J.I., Berchuck A., Kohler M.F., Boyd J. Nat. Genet. 7:98-102(1994) [PubMed: 8075649] [Abstract] Cited for: VARIANTS ENDOMETRIAL CANCER THR-617 AND VAL-711, VARIANT OVARIAN CANCER GLY-838.
[26]	"E-cadherin gene mutations in signet ring cell carcinoma of the stomach." Muta H., Noguchi M., Kanai Y., Ochiai A., Nawata H., Hirohashi S. Jpn. J. Cancer Res. 87:843-848(1996) [PubMed: 8797891] [Abstract] Cited for: VARIANT DIFFUSE GASTRIC CANCER PRO-193.
[27]	"Inactivation of the E-cadherin gene in primary gastric carcinomas and gastric carcinoma cell lines." Tamura G., Sakata K., Nishizuka S., Maesawa C., Suzuki Y., Iwaya T., Terashima M., Saito K., Satodate R. Jpn. J. Cancer Res. 87:1153-1159(1996) [PubMed: 9045944] [Abstract] Cited for: VARIANTS GASTRIC CARCINOMA ASP-400 DEL AND 418-ASP--PHE-423 DEL.
[28]	"E-cadherin gene alterations are rare events in thyroid tumors." Soares P., Berx G., van Roy F., Sobrinho-Simoes M. Int. J. Cancer 70:32-38(1997) [PubMed: 8985087] [Abstract] Cited for: VARIANT THYROID CANCER THR-592.
[29]	"E-cadherin germline mutations in familial gastric cancer." Guilford P.J., Hopkins J.B.W., Harraway J., McLeod M., McLeod N., Harawira P., Taite H., Scoular R., Miller A., Reeve A.E. Nature 392:402-405(1998) [PubMed: 9537325] [Abstract] Cited for: VARIANTS ASP-336 AND ILE-470.
[30]	"Germline mutations of E-cadherin gene in Korean familial gastric cancer patients." Yoon K.-A., Ku J.-L., Yang H.-K., Kim W.H., Park S.Y., Park J.-G. J. Hum. Genet. 44:177-180(1999) [PubMed: 10319582] [Abstract] Cited for: VARIANTS HDGC GLY-244 AND ALA-487.
[31]	"The E-cadherin gene (CDH1) variants T340A and L599V in gastric and colorectal cancer patients in Korea." Kim H.C., Wheeler J.M.D., Kim J.C., Ilyas M., Beck N.E., Kim B.S., Park K.C., Bodmer W.F. Gut 47:262-267(2000) [PubMed: 10896919] [Abstract] Cited for: VARIANT COLORECTAL CANCER ALA-340.
[32]	"Association of E-cadherin germ-line alterations with prostate cancer." Ikonen T., Matikainen M., Mononen N., Hyytinen E.R., Helin H.J., Tommola S., Tammela T.L., Pukkala E., Schleutker J., Kallioniemi O.-P., Koivisto P.A. Clin. Cancer Res. 7:3465-3471(2001) [PubMed: 11705864] [Abstract] Cited for: VARIANT ALA-270.
[33]	"A germline E-cadherin mutation in a family with gastric and colon cancer." Salahshor S., Hou H., Diep C.B., Loukola A., Zhang H., Liu T., Chen J., Iselius L., Rubio C., Lothe R.A., Aaltonen L., Sun X.F., Lindmark G., Lindblom A. Int. J. Mol. Med. 8:439-443(2001) [PubMed: 11562785] [Abstract] Cited for: VARIANT THR-592.
[34]	"Screening E-cadherin in gastric cancer families reveals germline mutations only in hereditary diffuse gastric cancer kindred." Oliveira C., Bordin M.C., Grehan N., Huntsman D., Suriano G., Machado J.C., Kiviluoto T., Aaltonen L., Jackson C.E., Seruca R., Caldas C. Hum. Mutat. 19:510-517(2002) [PubMed: 11968083] [Abstract] Cited for: VARIANT HDGC ALA-340.
[35]	"E-cadherin gene variants in gastric cancer families whose probands are diagnosed with diffuse gastric cancer." Yabuta T., Shinmura K., Tani M., Yamaguchi S., Yoshimura K., Katai H., Nakajima T., Mochiki E., Tsujinaka T., Takami M., Hirose K., Yamaguchi A., Takenoshita S., Yokota J. Int. J. Cancer 101:434-441(2002) [PubMed: 12216071] [Abstract] Cited for: VARIANT HDGC MET-832.
[36]	"Identification of CDH1 germline missense mutations associated with functional inactivation of the E-cadherin protein in young gastric cancer probands." Suriano G., Oliveira C., Ferreira P., Machado J.C., Bordin M.C., De Wever O., Bruyneel E.A., Moguilevsky N., Grehan N., Porter T.R., Richards F.M., Hruban R.H., Roviello F., Huntsman D., Mareel M., Carneiro F., Caldas C., Seruca R. Hum. Mol. Genet. 12:575-582(2003) [PubMed: 12588804] [Abstract] Cited for: VARIANTS GASTRIC CANCER THR-617 AND VAL-634, CHARACTERIZATION OF VARIANTS GASTRIC CANCER ALA-340; THR-617 AND VAL-634.
[37]	"Somatic sequence alterations in twenty-one genes selected by expression profile analysis of breast carcinomas." Chanock S.J., Burdett L., Yeager M., Llaca V., Langeroed A., Presswalla S., Kaaresen R., Strausberg R.L., Gerhard D.S., Kristensen V., Perou C.M., Boerresen-Dale A.-L. Breast Cancer Res. 9:R5-R5(2007) [PubMed: 17224074] [Abstract] Cited for: VARIANTS ILE-282 AND ASN-777.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

NIEHS-SNPs

Wikipedia

E-cadherin entry

Cross-references

Sequence databases

EMBLGenBankDDBJ

Z13009 mRNA. Translation: CAA78353.1.
Z18923 mRNA. Translation: CAA79356.1.
L08599 mRNA. Translation: AAA61259.1. Frameshift.
DQ090940 Genomic DNA. Translation: AAY68225.1.
L34545 Genomic DNA. Translation: AAA21764.1.
D49685 Genomic DNA. Translation: BAA08537.1.
Z35402 , Z35403, Z35404, Z35405, Z35406, Z35407, Z35408, Z35409, Z35410, Z35411, Z35412, Z35413, Z35414, Z35415 Genomic DNA. Translation: CAA84586.1.
X12790 mRNA. Translation: CAA31279.1.
X52279 mRNA. Translation: CAA36522.1.
S72492, S72397, S72491 Genomic DNA. Translation: AAD14108.1.

IPI

IPI00025861.

PIR

IJHUCE. S37654.

RefSeq

NP_004351.1.

UniGene

Hs.461086

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1O6S	X-ray	1.80	B	156-255	[»]
2O72	X-ray	2.00	A	155-367	[»]
2OMT	X-ray	2.00	B	156-255	[»]
2OMU	X-ray	1.80	B	156-255	[»]
2OMV	X-ray	1.90	B	156-255	[»]
2OMX	X-ray	1.70	B	156-258	[»]
2OMY	X-ray	1.70	B	156-255	[»]
2OMZ	X-ray	1.60	B	156-255	[»]

SMR

P12830. Positions 802-877.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP:477N.

IntAct

P12830. 30 interactions.

PTM databases

PhosphoSite

P12830.

Proteomic databases

PRIDE

P12830.

Genome annotation databases

Ensembl

ENSG00000039068. Homo sapiens. [Contig view]

GeneID

999.

KEGG

hsa:999.

NMPDR

fig|9606.3.peg.12460.

Organism-specific databases

GeneCards

GC16P067328.

H-InvDB

HIX0038521.

HGNC

HGNC:1748. CDH1.

HPA

CAB000087.
HPA004812.

MIM

137215. phenotype.
167000. phenotype.
192090. gene.
608089. phenotype.

Orphanet

26106. Gastric cancer, familial.

PharmGKB

PA26282.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P12830.

Enzyme and pathway databases

Pathway_Interaction_DB

a6b1_a6b4_integrin_pathway. a6b1 and a6b4 Integrin signaling.
arf6_traffickingpathway. Arf6 trafficking events.
fgf_pathway. FGF signaling pathway.

Reactome

REACT_13552. Integrin cell surface interactions.
REACT_578. Apoptosis.
REACT_6900. Signaling in Immune system.

Gene expression databases

ArrayExpress

P12830.

Bgee

P12830.

CleanEx

HS_CDH1.

GermOnline

ENSG00000039068. Homo sapiens.

Family and domain databases

InterPro

IPR002126. Cadherin.
IPR000233. Cadherin_C_term.
IPR014868. Cadherin_pro.
[Graphical view]

Gene3D

G3DSA:2.60.40.60. Cadherin. 4 hits.

Pfam

PF00028. Cadherin. 5 hits.
PF01049. Cadherin_C. 1 hit.
PF08758. Cadherin_pro. 1 hit.
[Graphical view]

PRINTS

PR00205. CADHERIN.

SMART

SM00112. CA. 4 hits.
[Graphical view]

PROSITE

PS00232. CADHERIN_1. 3 hits.
PS50268. CADHERIN_2. 5 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

4200.

PMAP-CutDB

P12830.

SOURCE

Search...

Entry information

Entry name

CADH1_HUMAN

Accession

Primary (citable) accession number: P12830
Secondary accession number(s): Q13799 , Q14216, Q15855, Q16194, Q4PJ14

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	July 1, 1993
Last modified:	June 16, 2009
This is version 125 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)