Q9R0T4 (CADH1_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cadherin-1

Alternative name(s):
Epithelial cadherin
Short name=E-cadherin
Uvomorulin
CD_antigen=CD324

Cleaved into the following 3 chains:

1. E-Cad/CTF1
2. E-Cad/CTF2
3. E-Cad/CTF3

Gene names

Name:

Cdh1

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	886 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. 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. The stable association of CTNNA1 is controversial as CTNNA1 was shown not to bind to F-actin when assembled in the complex. Alternatively, the CTNNA1-containing complex may be linked to F-actin by other proteins such as LIMA1. Interaction with PSEN1, cleaves CDH1 resulting in the disassociation of cadherin-based adherens junctions (CAJs). Interacts with AJAP1, CTNND1 and DLGAP5 By similarity. Interacts with TBC1D2. Interacts with LIMA1. Interacts with CAV1. Interacts with the TRPV4 and CTNNB1 complex By similarity. Interacts with PIP5K1C. Interacts with DDR1; this stabilizes CDH1 at the cell surface and inhibits its internalization By similarity. Interacts with RAB8B. Ref.4
Subcellular location	Cell junction. Cell membrane; Single-pass type I membrane protein. Endosome By similarity. Golgi apparatus › trans-Golgi network By similarity. 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. Colocalizes with RAB11A endosomes during its transport from the Golgi apparatus to the plasma membrane By similarity.
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.
Post-translational modification	N-glycosylation at Asn-641 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-758 By similarity.
Sequence similarities	Contains 5 cadherin domains.

Ontologies

Keywords
Biological process	Cell adhesion
Cellular component	Cell junction Cell membrane Endosome Golgi apparatus Membrane
Domain	Repeat Signal Transmembrane Transmembrane helix
Ligand	Calcium Metal-binding
PTM	Cleavage on pair of basic residues Disulfide bond Glycoprotein Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell-cell adhesion Traceable author statement PubMed 20299672. Source: DFLAT cellular response to amino acid stimulus Inferred from electronic annotation. Source: Compara cellular response to indole-3-methanol Inferred from electronic annotation. Source: Compara cellular response to lithium ion Inferred from electronic annotation. Source: Compara cochlea development Inferred from electronic annotation. Source: Compara homophilic cell adhesion Inferred from electronic annotation. Source: InterPro negative regulation of cell-cell adhesion Inferred from electronic annotation. Source: Compara neuron projection development Inferred from expression pattern PubMed 12387456. Source: RGD pituitary gland development Inferred from expression pattern PubMed 17373711. Source: RGD positive regulation of transcription factor import into nucleus Inferred from electronic annotation. Source: Compara positive regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: Compara protein homooligomerization Inferred from electronic annotation. Source: Compara protein localization to plasma membrane Inferred from electronic annotation. Source: Compara protein metabolic process Inferred from electronic annotation. Source: Compara regulation of branching involved in salivary gland morphogenesis Inferred from electronic annotation. Source: Compara regulation of cysteine-type endopeptidase activity involved in apoptotic process Inferred from electronic annotation. Source: Compara regulation of protein localization to cell surface Inferred from electronic annotation. Source: Compara regulation of water loss via skin Inferred from electronic annotation. Source: Compara response to drug Inferred from expression pattern PubMed 16671876. Source: RGD response to organic substance Inferred from expression pattern PubMed 16997938. Source: RGD response to toxic substance Inferred from expression pattern PubMed 17120308. Source: RGD salivary gland cavitation Inferred from electronic annotation. Source: Compara sensory perception of sound Inferred from electronic annotation. Source: Compara synapse assembly Inferred from mutant phenotype PubMed 12123610. Source: RGD tight junction assembly Inferred from electronic annotation. Source: Compara trophectodermal cell differentiation Inferred from electronic annotation. Source: Compara
Cellular_component	Golgi apparatus Inferred from electronic annotation. Source: UniProtKB-SubCell Schmidt-Lanterman incisure Inferred from electronic annotation. Source: Compara actin cytoskeleton Inferred from electronic annotation. Source: Compara aggresome Inferred from electronic annotation. Source: Compara apical junction complex Inferred from electronic annotation. Source: Compara apical part of cell Inferred from electronic annotation. Source: Compara axon terminus Inferred from electronic annotation. Source: Compara basolateral plasma membrane Inferred from electronic annotation. Source: Compara catenin complex Inferred from electronic annotation. Source: Compara cell surface Inferred from electronic annotation. Source: Compara cell-cell adherens junction Inferred from electronic annotation. Source: Compara cytoplasm Inferred from direct assay PubMed 17167984. Source: RGD endosome Inferred from electronic annotation. Source: UniProtKB-SubCell focal adhesion Inferred from electronic annotation. Source: Compara integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW internal side of plasma membrane Inferred from electronic annotation. Source: Compara lateral loop Inferred from electronic annotation. Source: Compara lateral plasma membrane Inferred from electronic annotation. Source: Compara node of Ranvier Inferred from electronic annotation. Source: Compara perinuclear region of cytoplasm Inferred from electronic annotation. Source: Compara plasma membrane Inferred from direct assay PubMed 17167984. Source: RGD trans-Golgi network Inferred from electronic annotation. Source: Compara
Molecular_function	calcium ion binding Inferred from electronic annotation. Source: Compara
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 23	23	Potential
	Propeptide	24 – 158	135	Potential		PRO_0000003719
	Chain	159 – 886	728	Cadherin-1		PRO_0000003720
	Chain	705 – 886	182	E-Cad/CTF1 Potential		PRO_0000236073
	Chain	736 – 886	151	E-Cad/CTF2 Potential		PRO_0000236074
	Chain	755 – 886	132	E-Cad/CTF3 Potential		PRO_0000236075
Regions
	Topological domain	24 – 713	690	Extracellular Potential
	Transmembrane	714 – 734	21	Helical; Potential
	Topological domain	735 – 886	152	Cytoplasmic Potential
	Domain	159 – 266	108	Cadherin 1
	Domain	267 – 379	113	Cadherin 2
	Domain	380 – 490	111	Cadherin 3
	Domain	491 – 597	107	Cadherin 4
	Domain	598 – 701	104	Cadherin 5
	Region	762 – 773	12	Required for binding CTNND1 and PSEN1 By similarity
	Region	815 – 886	72	Required for binding alpha, beta and By similarity
	Compositional bias	842 – 857	16	Ser-rich
Sites
	Metal binding	261	1	Calcium 1 By similarity
	Metal binding	261	1	Calcium 2 By similarity
	Metal binding	292	1	Calcium 3 By similarity
	Site	704 – 705	2	Cleavage; by a metalloproteinase By similarity
	Site	735 – 736	2	Cleavage; by gamma-secretase/PS1 By similarity
	Site	754 – 755	2	Cleavage; by caspase-3 By similarity
Amino acid modifications
	Modified residue	757	1	Phosphotyrosine; by SRC By similarity
	Modified residue	758	1	Phosphotyrosine; by SRC By similarity
	Modified residue	759	1	Phosphotyrosine; by SRC By similarity
	Modified residue	842	1	Phosphoserine By similarity
	Modified residue	844	1	Phosphoserine By similarity
	Modified residue	850	1	Phosphoserine By similarity
	Glycosylation	562	1	N-linked (GlcNAc...) Potential
	Glycosylation	641	1	N-linked (GlcNAc...) Potential

Sequences

	Sequence		Length	Mass (Da)
	Q9R0T4 [UniParc]. Last modified May 1, 2000. Version 1. Checksum: A9AEE28EB797A547	FASTA	886	98,715
	10 20 30 40 50 60 MGARCRSFSA LLLLLQVSSW LCQQPESESD SCRPGFSSEV YTFLVPERHL ERGHILGRVK 70 80 90 100 110 120 FEGCTGRPRT AFFSEDSRFK VSTDGVITVK RHLKLHKLET SFLVHAWDSS YRKLSTKVTL 130 140 150 160 170 180 KSLGHHHHRH HHRDPVSESN PELLTFPSFH QGLRRQKRDW VIPPINCPEN QKGEFPQRLV 190 200 210 220 230 240 QIKSNRDKET TVFYSITGPG ADKPPVGVFI IERETGWLKV TQPLDREAID KYLLYSHAVS 250 260 270 280 290 300 SNGEAVEDPM EIVVTVTDQN DNRPEFIQEV FEGSVAEGAL PGTSVMQVSA TDADDDINTY 310 320 330 340 350 360 NAAIAYTILS QDPELPHKNM FTVNRDTGVI SVVTSGLDRE SYPTYTLVVQ AADLQGEGLS 370 380 390 400 410 420 TTAKAVITVK DINDNAPIFN PSTYQGQVLE NEVGARIATL KVTDDDAPNT PAWNAVYTVV 430 440 450 460 470 480 NDPDHQFTVI TDPKTNEGIL KTAKGLDFEA KQQYILHVTV ENEEPFEGSL VPSTATVTVD 490 500 510 520 530 540 VVDVNEAPIF VPAEKRVEVP EDFGVGLEIA SYTAREPDTF MEQKITYRIW RDTANWLEIN 550 560 570 580 590 600 PETGVISTRA EMDREDSEHV KNSTYTALII ATDDGSPIAT GTGTLLLVLS DVNDNAPIPE 610 620 630 640 650 660 PRNMQFCQRN PKPHVITILD PDLPPNTSPF TAELTHGASV NWTIEYNDAE QESLILQPRK 670 680 690 700 710 720 DLEIGEYKIN LKLSDNQNKD QVTTLEVHVC DCEGTVNNCM KAISLEAGLQ VPAILGILGG 730 740 750 760 770 780 ILALLILILL LLLFLRRRTV VKEPLLPPDD DTRDNVYYYD EEGGGEEDQD FDLSQLHRGL 790 800 810 820 830 840 DARPEVIRND VAPTLMSMPQ YRPRPANPDE IGNFIDENLK AADSDPTAPP YDSLLVFDYE 850 860 870 880 GSGSEAASLS SLNSSESDQD QDYDYLNEWG NRFKKLADMY GGGEED

References

[1]	Asai K., Tada T., Yamamoto M., Obayashi M., Mizuno M., Toda A., Eimoto T., Kato T. Submitted (SEP-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Jejunum.
[2]	"Multiple cadherin superfamily members with unique expression profiles are produced in rat testis." Johnson K.J., Patel S.R., Boekelheide K. Endocrinology 141:675-683(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 769-872. Strain: Fischer 344. Tissue: Testis.
[3]	Gibbons K.L. Thesis (1997), University of Technology / Sydney, Australia Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 779-846. Tissue: Mammary tumor.
[4]	"Rab8B GTPase and junction dynamics in the testis." Lau A.S., Mruk D.D. Endocrinology 144:1549-1563(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH RAB8B.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AB017696 mRNA. Translation: BAA84920.1. AF177680 mRNA. Translation: AAF87055.1. AJ000540 mRNA. Translation: CAA04173.1.
IPI	IPI00206662.
RefSeq	NP_112624.1. NM_031334.1.
UniGene	Rn.1303.
3D structure databases
ProteinModelPortal	Q9R0T4.
SMR	Q9R0T4. Positions 159-376, 788-881.
ModBase	Search...
PTM databases
PhosphoSite	Q9R0T4.
Proteomic databases
PaxDb	Q9R0T4.
PRIDE	Q9R0T4.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000027346; ENSRNOP00000027346; ENSRNOG00000020151.
GeneID	83502.
KEGG	rno:83502.
UCSC	RGD:69279. rat.
Organism-specific databases
CTD	999.
RGD	69279. Cdh1.
Phylogenomic databases
eggNOG	NOG328838.
GeneTree	ENSGT00700000104066.
HOGENOM	HOG000231254.
HOVERGEN	HBG106438.
InParanoid	Q9R0T4.
KO	K05689.
OMA	DYNCLNE.
OrthoDB	EOG4GF3DT.
Gene expression databases
Genevestigator	Q9R0T4.
Family and domain databases
Gene3D	2.60.40.60. 6 hits. 4.10.900.10. 1 hit.
InterPro	IPR002126. Cadherin. IPR015919. Cadherin-like. IPR020894. Cadherin_CS. IPR000233. Cadherin_cytoplasmic-dom. IPR014868. Cadherin_pro_dom. IPR027397. Catenin_binding_dom. [Graphical view]
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. SM01055. Cadherin_pro. 1 hit. [Graphical view]
SUPFAM	SSF49313. Cadherin. 6 hits.
PROSITE	PS00232. CADHERIN_1. 3 hits. PS50268. CADHERIN_2. 5 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	615920.
PMAP-CutDB	Q9R0T4.

Entry information

Entry name

CADH1_RAT

Accession

Primary (citable) accession number: Q9R0T4
Secondary accession number(s): O35794, Q9JIV9

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 27, 2001
Last sequence update:	May 1, 2000
Last modified:	May 29, 2013
This is version 106 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program