Reviewed, UniProtKB/Swiss-Prot P09803 (CADH1_MOUSE)

Names and origin

Protein names

Recommended name:
    Cadherin-1
Alternative name(s):
    Epithelial cadherin
      Short name=E-cadherin
    Uvomorulin
    ARC-1
    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

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus

Protein attributes

Sequence length	884 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 By similarity. E-Cad/CTF2 promotes non-amyloidogenic degradation of Abeta precursors. Has a strong inhibitory effect on APP C99 and C83 production By similarity.
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 By similarity.
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 By similarity.
Tissue specificity	Non-neural epithelial tissues.
Developmental stage	In the testis, expression is highest in fetal gonad, then decreases 5-fold in newborn. Detectable in 7-day-old but not in 21-day-old or adult. Ref.5
Sequence similarities	Contains 5 cadherin domains.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell junction Cell membrane Membrane
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 Inferred from electronic annotation. Source: InterPro protein homooligomerization Inferred from direct assay. Source: MGI protein metabolic process Inferred from direct assay. Source: MGI regulation of branching involved in salivary gland morphogenesis Inferred from mutant phenotype. Source: MGI regulation of caspase activity Inferred from direct assay. Source: MGI salivary gland cavitation Inferred from mutant phenotype. Source: MGI trophectodermal cell differentiation Inferred from mutant phenotype. Source: MGI
Cellular component	apical part of cell Inferred from direct assay. Source: MGI cell-cell adherens junction Inferred from direct assay. Source: MGI integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	RPTP-like protein binding Inferred from physical interaction. Source: MGI beta-catenin binding Inferred from physical interaction. Source: MGI calcium ion binding Inferred from direct assay. Source: MGI protein phosphatase binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Ctnnb1	Q02248	4	EBI-984420,EBI-397872

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 23

23

Potential

Propeptide

24 – 156

133

Potential

PRO_0000003717

Chain

157 – 884

728

Cadherin-1

PRO_0000003718

Chain

703 – 884

182

E-Cad/CTF1 Potential

PRO_0000236070

Chain

734 – 884

151

E-Cad/CTF2 Potential

PRO_0000236071

Chain

753 – 884

132

E-Cad/CTF3 Potential

PRO_0000236072

Regions

Topological domain

157 – 709

553

Extracellular Potential

Transmembrane

710 – 733

24

Potential

Topological domain

734 – 884

151

Cytoplasmic Potential

Domain

157 – 264

108

Cadherin 1

Domain

265 – 377

113

Cadherin 2

Domain

378 – 488

111

Cadherin 3

Domain

489 – 595

107

Cadherin 4

Domain

596 – 699

104

Cadherin 5

Region

760 – 771

12

Required for binding CTNND1 and PSEN1 By similarity

Region

813 – 884

72

Required for binding alpha, beta and gamma catenins By similarity

Compositional bias

840 – 855

16

Ser-rich

Sites

Site

702 – 703

2

Cleavage; by a metalloproteinase By similarity

Site

733 – 734

2

Cleavage; by gamma-secretase/PS1 By similarity

Site

752 – 753

2

Cleavage; by caspase-3 By similarity

Amino acid modifications

Modified residue

840

1

Phosphoserine

Modified residue

842

1

Phosphoserine

Modified residue

848

1

Phosphoserine

Glycosylation

560

1

N-linked (GlcNAc...) Potential

Glycosylation

639

1

N-linked (GlcNAc...) Potential

Experimental info

Sequence conflict

267

1

E → P in CAA43292. Ref.2

Sequence conflict

272

1

S → F in CAA43292. Ref.2

Secondary structure

1

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884

Helix Strand Turn

Details...

Beta strand

163 – 166

4

Beta strand

171 – 179

9

Helix

183 – 186

4

Beta strand

190 – 197

8

Turn

198 – 200

3

Beta strand

201 – 203

3

Beta strand

206 – 209

4

Turn

211 – 213

3

Beta strand

215 – 218

4

Turn

224 – 226

3

Beta strand

228 – 238

11

Beta strand

248 – 255

8

Beta strand

263 – 265

3

Beta strand

267 – 274

8

Beta strand

282 – 285

4

Turn

294 – 296

3

Beta strand

303 – 311

9

Beta strand

318 – 321

4

Turn

323 – 325

3

Beta strand

327 – 330

4

Turn

337 – 339

3

Beta strand

342 – 350

9

Helix

352 – 354

3

Beta strand

358 – 368

11

Helix

818 – 822

5

Turn

864 – 866

3

Helix

869 – 871

3

Helix

872 – 877

6

Sequences

	Sequence		Length	Mass (Da)
	P09803-1 [UniParc]. Last modified July 1, 1989. Version 1. Checksum: 7A6444148D3D5983	FASTA	884	98,256
	10 20 30 40 50 60 MGARCRSFSA LLLLLQVSSW LCQELEPESC SPGFSSEVYT FPVPERHLER GHVLGRVRFE 70 80 90 100 110 120 GCTGRPRTAF FSEDSRFKVA TDGTITVKRH LKLHKLETSF LVRARDSSHR ELSTKVTLKS 130 140 150 160 170 180 MGHHHHRHHH RDPASESNPE LLMFPSVYPG LRRQKRDWVI PPISCPENEK GEFPKNLVQI 190 200 210 220 230 240 KSNRDKETKV FYSITGQGAD KPPVGVFIIE RETGWLKVTQ PLDREAIAKY ILYSHAVSSN 250 260 270 280 290 300 GEAVEDPMEI VITVTDQNDN RPEFTQEVFE GSVAEGAVPG TSVMKVSATD ADDDVNTYNA 310 320 330 340 350 360 AIAYTIVSQD PELPHKNMFT VNRDTGVISV LTSGLDRESY PTYTLVVQAA DLQGEGLSTT 370 380 390 400 410 420 AKAVITVKDI NDNAPVFNPS TYQGQVPENE VNARIATLKV TDDDAPNTPA WKAVYTVVND 430 440 450 460 470 480 PDQQFVVVTD PTTNDGILKT AKGLDFEAKQ QYILHVRVEN EEPFEGSLVP STATVTVDVV 490 500 510 520 530 540 DVNEAPIFMP AERRVEVPED FGVGQEITSY TAREPDTFMD QKITYRIWRD TANWLEINPE 550 560 570 580 590 600 TGAIFTRAEM DREDAEHVKN STYVALIIAT DDGSPIATGT GTLLLVLLDV NDNAPIPEPR 610 620 630 640 650 660 NMQFCQRNPQ PHIITILDPD LPPNTSPFTA ELTHGASVNW TIEYNDAAQE SLILQPRKDL 670 680 690 700 710 720 EIGEYKIHLK LADNQNKDQV TTLDVHVCDC EGTVNNCMKA GIVAAGLQVP AILGILGGIL 730 740 750 760 770 780 ALLILILLLL LFLRRRTVVK EPLLPPDDDT RDNVYYYDEE GGGEEDQDFD LSQLHRGLDA 790 800 810 820 830 840 RPEVTRNDVA PTLMSVPQYR PRPANPDEIG NFIDENLKAA DSDPTAPPYD SLLVFDYEGS 850 860 870 880 GSEAASLSSL NSSESDQDQD YDYLNEWGNR FKKLADMYGG GEDD

References

[1]	"Transformation of cell adhesion properties by exogenously introduced E-cadherin cDNA." Nagafuchi A., Shirayoshi Y., Okazari K., Yasuda K., Takeichi M. Nature 329:341-343(1987) [PubMed: 3498123] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: ICR.
[2]	"The structure of the gene coding for the mouse cell adhesion molecule uvomorulin." Ringwald M., Baribault H., Schmidt C., Kemler R. Nucleic Acids Res. 19:6533-6539(1991) [PubMed: 1754391] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: 129/Sv.
[3]	"The structure of cell adhesion molecule uvomorulin. Insights into the molecular mechanism of Ca2+-dependent cell adhesion." Ringwald M., Schuh R., Vestweber D., Eistetter H., Lottspeich F., Engel J., Doelz R., Jaehnig F., Epplen J., Mayer S., Mueller C., Kemler R. EMBO J. 6:3647-3653(1987) [PubMed: 3501370] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 174-884, PROTEIN SEQUENCE OF 157-181.
[4]	"The E-cadherin promoter: functional analysis of a G.C-rich region and an epithelial cell-specific palindromic regulatory element." Behrens J., Loewrick O., Klein-Hitpass L., Birchmeier W. Proc. Natl. Acad. Sci. U.S.A. 88:11495-11499(1991) [PubMed: 1763063] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-15.
[5]	"A comprehensive survey of the cadherins expressed in the testes of fetal, immature, and adult mice utilizing the polymerase chain reaction." Munro S.B., Blaschuk O.W. Biol. Reprod. 55:822-827(1996) [PubMed: 8879495] [Abstract] Cited for: DEVELOPMENTAL STAGE. Strain: C57BL/6. Tissue: Testis.
[6]	"Structural basis of calcium-induced E-cadherin rigidification and dimerization." Nagar B., Overduin M., Ikura M., Rini J.M. Nature 380:360-364(1996) [PubMed: 8598933] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 157-370.
[7]	"1H, 15N and 13C resonance assignments and monomeric structure of the amino-terminal extracellular domain of epithelial cadherin." Overduin M., Tong K.I., Kay C.M., Ikura M. J. Biomol. NMR 7:173-189(1996) [PubMed: 8785495] [Abstract] Cited for: STRUCTURE BY NMR OF 157-260.
[8]	"The structure of the beta-catenin/E-cadherin complex and the molecular basis of diverse ligand recognition by beta-catenin." Huber A.H., Weis W.I. Cell 105:391-402(2001) [PubMed: 11348595] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 577-728 IN COMPLEX WITH CTNNB1, PHOSPHORYLATION.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X06115 mRNA. Translation: CAA29488.1.
X60961 , X60962, X60963, X60964, X60965, X60966, X60967, X60968, X60969, X60970, X60971, X60972, X60973, X60974, X60975 Genomic DNA. Translation: CAA43292.1.
X06339 mRNA. Translation: CAA29645.1.
M81449 Genomic DNA. Translation: AAA37352.1.

IPI

IPI00318626.

PIR

IJMSCE. S04528.
S34438.

RefSeq

NP_033994.1.

UniGene

Mm.35605

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EDH	X-ray	2.00	A/B	156-380	[»]
1FF5	X-ray	2.93	A/B	157-374	[»]
1I7W	X-ray	2.00	B/D	734-884	[»]
1I7X	X-ray	3.00	B/D	734-884	[»]
1Q1P	X-ray	3.20	A	158-369	[»]
1SUH	NMR	-	A	156-300	[»]
2OMW	X-ray	1.85	B	158-256	[»]
2QVF	X-ray	2.40	B	157-369	[»]
3IFQ	X-ray	2.80	C/D	778-884	[»]

SMR

P09803. Positions 27-156, 272-481.

DisProt

DP00159.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29635N.

IntAct

P09803. 3 interactions.

STRING

P09803.

PTM databases

PhosphoSite

P09803.

Proteomic databases

PRIDE

P09803.

Genome annotation databases

Ensembl

ENSMUST00000000312; ENSMUSP00000000312; ENSMUSG00000000303; Mus musculus. [Genome view]

GeneID

12550.

KEGG

mmu:12550.

Organism-specific databases

CTD

12550.

MGI

MGI:88354. Cdh1.

Phylogenomic databases

eggNOG

roNOG05681.

HOGENOM

HBG505775.

HOVERGEN

P09803.

InParanoid

P09803.

Gene expression databases

ArrayExpress

P09803.

Bgee

P09803.

CleanEx

MM_CDH1.

Genevestigator

P09803.

GermOnline

ENSMUSG00000000303. Mus musculus.

Family and domain databases

InterPro

IPR002126. Cadherin.
IPR015919. Cadherin-like.
IPR020894. Cadherin_CS.
IPR000233. Cadherin_cytoplasmic-dom.
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. 4 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

SOURCE

Search...

Entry information

Entry name

CADH1_MOUSE

Accession

Primary (citable) accession number: P09803
Secondary accession number(s): Q61377

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 1, 1989
Last sequence update:	July 1, 1989
Last modified:	January 19, 2010
This is version 115 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)