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Protein

Cadherin-1

Gene

Cdh1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Cadherins are calcium-dependent cell adhesion proteins (PubMed:11976333). 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 (PubMed:11976333). Has a potent invasive suppressor role. It is a ligand for integrin alpha-E/beta-7 (By similarity).By similarity1 Publication
E-Cad/CTF2 promotes non-amyloidogenic degradation of Abeta precursors. Has a strong inhibitory effect on APP C99 and C83 production (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi259Calcium 11
Metal bindingi259Calcium 21
Metal bindingi290Calcium 31

GO - Molecular functioni

  • alpha-catenin binding Source: MGI
  • ankyrin binding Source: MGI
  • beta-catenin binding Source: CAFA
  • cadherin binding Source: MGI
  • calcium ion binding Source: MGI
  • cell adhesion molecule binding Source: MGI
  • cytoskeletal protein binding Source: MGI
  • gamma-catenin binding Source: MGI
  • GTPase activating protein binding Source: MGI
  • protein domain specific binding Source: MGI
  • protein phosphatase binding Source: UniProtKB

GO - Biological processi

  • adherens junction organization Source: MGI
  • bicellular tight junction assembly Source: MGI
  • calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules Source: MGI
  • cellular response to amino acid stimulus Source: MGI
  • cellular response to indole-3-methanol Source: MGI
  • cellular response to lithium ion Source: MGI
  • cochlea development Source: MGI
  • decidualization Source: CACAO
  • embryo implantation Source: CACAO
  • epithelial cell morphogenesis Source: MGI
  • establishment of protein localization to plasma membrane Source: UniProtKB
  • homophilic cell adhesion via plasma membrane adhesion molecules Source: InterPro
  • intestinal epithelial cell development Source: MGI
  • in utero embryonic development Source: MGI
  • negative regulation of canonical Wnt signaling pathway Source: MGI
  • negative regulation of cell-cell adhesion Source: MGI
  • negative regulation of epithelial cell proliferation Source: MGI
  • negative regulation of protein processing Source: MGI
  • positive regulation of cell-cell adhesion Source: MGI
  • positive regulation of transcription, DNA-templated Source: MGI
  • positive regulation of transcription factor import into nucleus Source: MGI
  • protein homooligomerization Source: MGI
  • protein localization to plasma membrane Source: MGI
  • protein metabolic process Source: MGI
  • regulation of branching involved in salivary gland morphogenesis Source: MGI
  • regulation of cysteine-type endopeptidase activity involved in apoptotic process Source: MGI
  • regulation of immune response Source: Reactome
  • regulation of neuron migration Source: MGI
  • regulation of protein localization Source: MGI
  • regulation of protein localization to cell surface Source: MGI
  • regulation of water loss via skin Source: MGI
  • salivary gland cavitation Source: MGI
  • sensory perception of sound Source: MGI
  • single organismal cell-cell adhesion Source: MGI
  • trophectodermal cell differentiation Source: MGI
  • uterine epithelium development Source: CACAO

Keywordsi

Biological processCell adhesion
LigandCalcium, Metal-binding

Enzyme and pathway databases

ReactomeiR-MMU-198933. Immunoregulatory interactions between a Lymphoid and a non-Lymphoid cell.

Names & Taxonomyi

Protein namesi
Recommended name:
Cadherin-1
Alternative name(s):
ARC-1
Epithelial cadherin
Short name:
E-cadherin
Uvomorulin
CD_antigen: CD324
Cleaved into the following 3 chains:
Gene namesi
Name:Cdh1
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Unplaced

Organism-specific databases

MGIiMGI:88354. Cdh1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini157 – 709ExtracellularSequence analysisAdd BLAST553
Transmembranei710 – 733HelicalSequence analysisAdd BLAST24
Topological domaini734 – 884CytoplasmicSequence analysisAdd BLAST151

Keywords - Cellular componenti

Cell junction, Cell membrane, Endosome, Golgi apparatus, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 23Sequence analysisAdd BLAST23
PropeptideiPRO_000000371724 – 156Sequence analysisAdd BLAST133
ChainiPRO_0000003718157 – 884Cadherin-1Add BLAST728
ChainiPRO_0000236070703 – 884E-Cad/CTF1Sequence analysisAdd BLAST182
ChainiPRO_0000236071734 – 884E-Cad/CTF2Sequence analysisAdd BLAST151
ChainiPRO_0000236072753 – 884E-Cad/CTF3Sequence analysisAdd BLAST132

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi560N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi639N-linked (GlcNAc...) asparagineSequence analysis1
Modified residuei755Phosphotyrosine; by SRCBy similarity1
Modified residuei756Phosphotyrosine; by SRCBy similarity1
Modified residuei757Phosphotyrosine; by SRCBy similarity1
Modified residuei772PhosphoserineBy similarity1
Modified residuei795PhosphoserineBy similarity1
Modified residuei840Phosphoserine1 Publication1
Modified residuei842Phosphoserine1 Publication1
Modified residuei848Phosphoserine1 Publication1

Post-translational modificationi

N-glycosylation at Asn-639 is essential for expression, folding and trafficking.By similarity
Ubiquitinated by a SCF complex containing SKP2, which requires prior phosphorylation by CK1/CSNK1A1. Ubiquitinated by CBLL1/HAKAI, requires prior phosphorylation at Tyr-756 (By similarity).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei702 – 703Cleavage; by a metalloproteinaseBy similarity2
Sitei733 – 734Cleavage; by gamma-secretase/PS1By similarity2
Sitei752 – 753Cleavage; by caspase-3By similarity2

Keywords - PTMi

Cleavage on pair of basic residues, Disulfide bond, Glycoprotein, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiP09803.
PaxDbiP09803.
PeptideAtlasiP09803.
PRIDEiP09803.

PTM databases

iPTMnetiP09803.
PhosphoSitePlusiP09803.

Expressioni

Tissue specificityi

Non-neural epithelial tissues.

Developmental stagei

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.1 Publication

Gene expression databases

CleanExiMM_CDH1.

Interactioni

Subunit structurei

Homodimer; disulfide-linked (By similarity). Component of an E-cadherin/ catenin adhesion complex composed of at least E-cadherin/CDH1, beta-catenin/CTNNB1 or gamma-catenin/JUP, and potentially alpha-catenin/CTNNA1; the complex is located to adherens junctions (PubMed:7982500, PubMed:19759396). Interacts with the TRPV4 and CTNNB1 complex (PubMed:20413591, PubMed:11348595). Interacts with CTNND1 (By similarity). The stable association of CTNNA1 is controversial as CTNNA1 was shown not to bind to F-actin when assembled in the complex (PubMed:16325582). Alternatively, the CTNNA1-containing complex may be linked to F-actin by other proteins such as LIMA1 (PubMed:18093941). Interaction with PSEN1, cleaves CDH1 resulting in the disassociation of cadherin-based adherens junctions (CAJs) (By similarity). Interacts with AJAP1 and DLGAP5 (By similarity). Interacts with TBC1D2 (By similarity). Interacts with LIMA1 (By similarity). Interacts with CAV1 (By similarity). Interacts with PIP5K1C (By similarity). Interacts with RAB8B (By similarity). Interacts with DDR1; this stabilizes CDH1 at the cell surface and inhibits its internalization (By similarity). Interacts with RAPGEF2 (By similarity). Interacts with KLRG1 (By similarity).By similarity6 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • alpha-catenin binding Source: MGI
  • ankyrin binding Source: MGI
  • beta-catenin binding Source: CAFA
  • cadherin binding Source: MGI
  • cell adhesion molecule binding Source: MGI
  • cytoskeletal protein binding Source: MGI
  • gamma-catenin binding Source: MGI
  • GTPase activating protein binding Source: MGI
  • protein domain specific binding Source: MGI
  • protein phosphatase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi198631. 38 interactors.
CORUMiP09803.
DIPiDIP-29635N.
IntActiP09803. 35 interactors.
MINTiMINT-121804.
STRINGi10090.ENSMUSP00000000312.

Structurei

Secondary structure

1884
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi160 – 166Combined sources7
Beta strandi171 – 179Combined sources9
Helixi183 – 186Combined sources4
Beta strandi190 – 197Combined sources8
Turni198 – 200Combined sources3
Beta strandi201 – 203Combined sources3
Beta strandi206 – 209Combined sources4
Turni211 – 213Combined sources3
Beta strandi215 – 218Combined sources4
Turni224 – 226Combined sources3
Beta strandi228 – 238Combined sources11
Turni239 – 241Combined sources3
Beta strandi243 – 245Combined sources3
Beta strandi248 – 255Combined sources8
Beta strandi263 – 265Combined sources3
Beta strandi267 – 274Combined sources8
Beta strandi282 – 285Combined sources4
Turni294 – 296Combined sources3
Helixi298 – 300Combined sources3
Beta strandi303 – 311Combined sources9
Beta strandi314 – 316Combined sources3
Beta strandi318 – 321Combined sources4
Turni323 – 325Combined sources3
Beta strandi327 – 330Combined sources4
Turni337 – 339Combined sources3
Beta strandi342 – 350Combined sources9
Helixi352 – 354Combined sources3
Beta strandi358 – 368Combined sources11
Beta strandi376 – 389Combined sources14
Beta strandi396 – 398Combined sources3
Turni409 – 411Combined sources3
Beta strandi413 – 419Combined sources7
Beta strandi425 – 429Combined sources5
Turni431 – 433Combined sources3
Beta strandi436 – 442Combined sources7
Turni446 – 448Combined sources3
Beta strandi450 – 462Combined sources13
Beta strandi471 – 480Combined sources10
Beta strandi487 – 492Combined sources6
Beta strandi494 – 498Combined sources5
Beta strandi506 – 509Combined sources4
Beta strandi524 – 529Combined sources6
Beta strandi535 – 537Combined sources3
Turni539 – 541Combined sources3
Beta strandi543 – 546Combined sources4
Turni555 – 557Combined sources3
Beta strandi560 – 570Combined sources11
Beta strandi573 – 575Combined sources3
Beta strandi579 – 588Combined sources10
Beta strandi596 – 598Combined sources3
Beta strandi603 – 608Combined sources6
Beta strandi612 – 617Combined sources6
Beta strandi624 – 627Combined sources4
Beta strandi631 – 634Combined sources4
Beta strandi637 – 639Combined sources3
Beta strandi641 – 643Combined sources3
Beta strandi649 – 655Combined sources7
Beta strandi668 – 670Combined sources3
Beta strandi673 – 675Combined sources3
Beta strandi684 – 688Combined sources5
Beta strandi785 – 789Combined sources5
Turni806 – 808Combined sources3
Helixi818 – 822Combined sources5
Beta strandi824 – 827Combined sources4
Beta strandi830 – 834Combined sources5
Turni864 – 866Combined sources3
Helixi869 – 871Combined sources3
Helixi872 – 877Combined sources6

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1EDHX-ray2.00A/B156-380[»]
1FF5X-ray2.93A/B157-374[»]
1I7WX-ray2.00B/D734-884[»]
1I7XX-ray3.00B/D734-884[»]
1Q1PX-ray3.20A158-369[»]
1SUHNMR-A156-300[»]
2OMWX-ray1.85B158-256[»]
2QVFX-ray2.40B157-369[»]
3IFQX-ray2.80C/D778-884[»]
3LNEX-ray2.00A157-369[»]
3LNFX-ray2.50A/B157-369[»]
3LNGX-ray2.70A/B157-369[»]
3LNHX-ray2.60A/B157-369[»]
3LNIX-ray2.30A/B157-369[»]
3Q2LX-ray2.70A/B157-369[»]
3Q2NX-ray2.73A/B157-369[»]
3Q2VX-ray3.40A/B157-700[»]
3QRBX-ray1.80A/B157-369[»]
4QD2X-ray2.40E/J157-369[»]
DisProtiDP00159.
ProteinModelPortaliP09803.
SMRiP09803.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP09803.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini157 – 264Cadherin 1PROSITE-ProRule annotationAdd BLAST108
Domaini265 – 377Cadherin 2PROSITE-ProRule annotationAdd BLAST113
Domaini378 – 488Cadherin 3PROSITE-ProRule annotationAdd BLAST111
Domaini489 – 595Cadherin 4PROSITE-ProRule annotationAdd BLAST107
Domaini596 – 699Cadherin 5PROSITE-ProRule annotationAdd BLAST104

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni760 – 771Required for binding CTNND1 and PSEN1By similarityAdd BLAST12
Regioni813 – 884Required for binding alpha, beta and gamma cateninsBy similarityAdd BLAST72

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi840 – 855Ser-richAdd BLAST16

Domaini

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.

Keywords - Domaini

Repeat, Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3594. Eukaryota.
ENOG410XQHI. LUCA.
HOGENOMiHOG000231254.
HOVERGENiHBG106438.
InParanoidiP09803.
KOiK05689.
PhylomeDBiP09803.
TreeFamiTF316817.

Family and domain databases

Gene3Di4.10.900.10. 1 hit.
InterProiView protein in InterPro
IPR002126. Cadherin.
IPR015919. Cadherin-like.
IPR020894. Cadherin_CS.
IPR000233. Cadherin_cytoplasmic-dom.
IPR014868. Cadherin_pro_dom.
IPR027397. Catenin_binding_dom.
PfamiView protein in Pfam
PF00028. Cadherin. 5 hits.
PF01049. Cadherin_C. 1 hit.
PF08758. Cadherin_pro. 1 hit.
PRINTSiPR00205. CADHERIN.
SMARTiView protein in SMART
SM00112. CA. 4 hits.
SM01055. Cadherin_pro. 1 hit.
SUPFAMiSSF49313. SSF49313. 6 hits.
PROSITEiView protein in PROSITE
PS00232. CADHERIN_1. 3 hits.
PS50268. CADHERIN_2. 4 hits.

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P09803-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGARCRSFSA LLLLLQVSSW LCQELEPESC SPGFSSEVYT FPVPERHLER
60 70 80 90 100
GHVLGRVRFE GCTGRPRTAF FSEDSRFKVA TDGTITVKRH LKLHKLETSF
110 120 130 140 150
LVRARDSSHR ELSTKVTLKS MGHHHHRHHH RDPASESNPE LLMFPSVYPG
160 170 180 190 200
LRRQKRDWVI PPISCPENEK GEFPKNLVQI KSNRDKETKV FYSITGQGAD
210 220 230 240 250
KPPVGVFIIE RETGWLKVTQ PLDREAIAKY ILYSHAVSSN GEAVEDPMEI
260 270 280 290 300
VITVTDQNDN RPEFTQEVFE GSVAEGAVPG TSVMKVSATD ADDDVNTYNA
310 320 330 340 350
AIAYTIVSQD PELPHKNMFT VNRDTGVISV LTSGLDRESY PTYTLVVQAA
360 370 380 390 400
DLQGEGLSTT AKAVITVKDI NDNAPVFNPS TYQGQVPENE VNARIATLKV
410 420 430 440 450
TDDDAPNTPA WKAVYTVVND PDQQFVVVTD PTTNDGILKT AKGLDFEAKQ
460 470 480 490 500
QYILHVRVEN EEPFEGSLVP STATVTVDVV DVNEAPIFMP AERRVEVPED
510 520 530 540 550
FGVGQEITSY TAREPDTFMD QKITYRIWRD TANWLEINPE TGAIFTRAEM
560 570 580 590 600
DREDAEHVKN STYVALIIAT DDGSPIATGT GTLLLVLLDV NDNAPIPEPR
610 620 630 640 650
NMQFCQRNPQ PHIITILDPD LPPNTSPFTA ELTHGASVNW TIEYNDAAQE
660 670 680 690 700
SLILQPRKDL EIGEYKIHLK LADNQNKDQV TTLDVHVCDC EGTVNNCMKA
710 720 730 740 750
GIVAAGLQVP AILGILGGIL ALLILILLLL LFLRRRTVVK EPLLPPDDDT
760 770 780 790 800
RDNVYYYDEE GGGEEDQDFD LSQLHRGLDA RPEVTRNDVA PTLMSVPQYR
810 820 830 840 850
PRPANPDEIG NFIDENLKAA DSDPTAPPYD SLLVFDYEGS GSEAASLSSL
860 870 880
NSSESDQDQD YDYLNEWGNR FKKLADMYGG GEDD
Length:884
Mass (Da):98,256
Last modified:July 1, 1989 - v1
Checksum:i7A6444148D3D5983
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti267E → P in CAA43292 (PubMed:1754391).Curated1
Sequence conflicti272S → F in CAA43292 (PubMed:1754391).Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS22638.1.
PIRiS04528. IJMSCE.
S34438.
RefSeqiNP_033994.1. NM_009864.3.
UniGeneiMm.35605.

Genome annotation databases

GeneIDi12550.
KEGGimmu:12550.
UCSCiuc009ngi.1. mouse.

Similar proteinsi

Entry informationi

Entry nameiCADH1_MOUSE
AccessioniPrimary (citable) accession number: P09803
Secondary accession number(s): Q61377
Entry historyiIntegrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: July 1, 1989
Last modified: September 27, 2017
This is version 195 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references