CADH1_CANLF
ID CADH1_CANLF Reviewed; 885 AA.
AC F1PAA9;
DT 16-OCT-2013, integrated into UniProtKB/Swiss-Prot.
DT 31-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 86.
DE RecName: Full=Cadherin-1;
DE AltName: Full=Epithelial cadherin;
DE Short=E-cadherin;
DE AltName: Full=Uvomorulin;
DE AltName: CD_antigen=CD324;
DE Contains:
DE RecName: Full=E-Cad/CTF1;
DE Contains:
DE RecName: Full=E-Cad/CTF2;
DE Contains:
DE RecName: Full=E-Cad/CTF3;
DE Flags: Precursor;
GN Name=CDH1;
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Boxer;
RX PubMed=16341006; DOI=10.1038/nature04338;
RA Lindblad-Toh K., Wade C.M., Mikkelsen T.S., Karlsson E.K., Jaffe D.B.,
RA Kamal M., Clamp M., Chang J.L., Kulbokas E.J. III, Zody M.C., Mauceli E.,
RA Xie X., Breen M., Wayne R.K., Ostrander E.A., Ponting C.P., Galibert F.,
RA Smith D.R., deJong P.J., Kirkness E.F., Alvarez P., Biagi T., Brockman W.,
RA Butler J., Chin C.-W., Cook A., Cuff J., Daly M.J., DeCaprio D., Gnerre S.,
RA Grabherr M., Kellis M., Kleber M., Bardeleben C., Goodstadt L., Heger A.,
RA Hitte C., Kim L., Koepfli K.-P., Parker H.G., Pollinger J.P.,
RA Searle S.M.J., Sutter N.B., Thomas R., Webber C., Baldwin J., Abebe A.,
RA Abouelleil A., Aftuck L., Ait-Zahra M., Aldredge T., Allen N., An P.,
RA Anderson S., Antoine C., Arachchi H., Aslam A., Ayotte L., Bachantsang P.,
RA Barry A., Bayul T., Benamara M., Berlin A., Bessette D., Blitshteyn B.,
RA Bloom T., Blye J., Boguslavskiy L., Bonnet C., Boukhgalter B., Brown A.,
RA Cahill P., Calixte N., Camarata J., Cheshatsang Y., Chu J., Citroen M.,
RA Collymore A., Cooke P., Dawoe T., Daza R., Decktor K., DeGray S.,
RA Dhargay N., Dooley K., Dooley K., Dorje P., Dorjee K., Dorris L.,
RA Duffey N., Dupes A., Egbiremolen O., Elong R., Falk J., Farina A., Faro S.,
RA Ferguson D., Ferreira P., Fisher S., FitzGerald M., Foley K., Foley C.,
RA Franke A., Friedrich D., Gage D., Garber M., Gearin G., Giannoukos G.,
RA Goode T., Goyette A., Graham J., Grandbois E., Gyaltsen K., Hafez N.,
RA Hagopian D., Hagos B., Hall J., Healy C., Hegarty R., Honan T., Horn A.,
RA Houde N., Hughes L., Hunnicutt L., Husby M., Jester B., Jones C., Kamat A.,
RA Kanga B., Kells C., Khazanovich D., Kieu A.C., Kisner P., Kumar M.,
RA Lance K., Landers T., Lara M., Lee W., Leger J.-P., Lennon N., Leuper L.,
RA LeVine S., Liu J., Liu X., Lokyitsang Y., Lokyitsang T., Lui A.,
RA Macdonald J., Major J., Marabella R., Maru K., Matthews C., McDonough S.,
RA Mehta T., Meldrim J., Melnikov A., Meneus L., Mihalev A., Mihova T.,
RA Miller K., Mittelman R., Mlenga V., Mulrain L., Munson G., Navidi A.,
RA Naylor J., Nguyen T., Nguyen N., Nguyen C., Nguyen T., Nicol R., Norbu N.,
RA Norbu C., Novod N., Nyima T., Olandt P., O'Neill B., O'Neill K., Osman S.,
RA Oyono L., Patti C., Perrin D., Phunkhang P., Pierre F., Priest M.,
RA Rachupka A., Raghuraman S., Rameau R., Ray V., Raymond C., Rege F.,
RA Rise C., Rogers J., Rogov P., Sahalie J., Settipalli S., Sharpe T.,
RA Shea T., Sheehan M., Sherpa N., Shi J., Shih D., Sloan J., Smith C.,
RA Sparrow T., Stalker J., Stange-Thomann N., Stavropoulos S., Stone C.,
RA Stone S., Sykes S., Tchuinga P., Tenzing P., Tesfaye S., Thoulutsang D.,
RA Thoulutsang Y., Topham K., Topping I., Tsamla T., Vassiliev H.,
RA Venkataraman V., Vo A., Wangchuk T., Wangdi T., Weiand M., Wilkinson J.,
RA Wilson A., Yadav S., Yang S., Yang X., Young G., Yu Q., Zainoun J.,
RA Zembek L., Zimmer A., Lander E.S.;
RT "Genome sequence, comparative analysis and haplotype structure of the
RT domestic dog.";
RL Nature 438:803-819(2005).
RN [2]
RP INTERACTION WITH RAPGEF2.
RX PubMed=10873669; DOI=10.1006/bbrc.2000.3002;
RA Kawajiri A., Itoh N., Fukata M., Nakagawa M., Yamaga M., Iwamatsu A.,
RA Kaibuchi K.;
RT "Identification of a novel beta-catenin-interacting protein.";
RL Biochem. Biophys. Res. Commun. 273:712-717(2000).
CC -!- FUNCTION: Cadherins are calcium-dependent cell adhesion proteins. They
CC preferentially interact with themselves in a homophilic manner in
CC connecting cells; cadherins may thus contribute to the sorting of
CC heterogeneous cell types. CDH1 is involved in mechanisms regulating
CC cell-cell adhesions, mobility and proliferation of epithelial cells.
CC Has a potent invasive suppressor role. It is a ligand for integrin
CC alpha-E/beta-7. {ECO:0000250|UniProtKB:P12830}.
CC -!- FUNCTION: E-Cad/CTF2 promotes non-amyloidogenic degradation of Abeta
CC precursors. Has a strong inhibitory effect on APP C99 and C83
CC production. {ECO:0000250|UniProtKB:P12830}.
CC -!- SUBUNIT: Homodimer; disulfide-linked (By similarity). Component of an
CC E-cadherin/ catenin adhesion complex composed of at least E-
CC cadherin/CDH1, beta-catenin/CTNNB1 or gamma-catenin/JUP, and
CC potentially alpha-catenin/CTNNA1; the complex is located to adherens
CC junctions (By similarity). Interacts with the TRPV4 and CTNNB1 complex
CC (By similarity). Interacts with CTNND1 (By similarity). The stable
CC association of CTNNA1 is controversial as CTNNA1 was shown not to bind
CC to F-actin when assembled in the complex (By similarity).
CC Alternatively, the CTNNA1-containing complex may be linked to F-actin
CC by other proteins such as LIMA1 (By similarity). Interaction with
CC PSEN1, cleaves CDH1 resulting in the disassociation of cadherin-based
CC adherens junctions (CAJs) (By similarity). Interacts with AJAP1 and
CC DLGAP5 (By similarity). Interacts with TBC1D2 (By similarity).
CC Interacts with LIMA1 (By similarity). Interacts with CAV1 (By
CC similarity). Interacts with PIP5K1C (By similarity). Interacts with
CC RAB8B (By similarity). Interacts with DDR1; this stabilizes CDH1 at the
CC cell surface and inhibits its internalization (By similarity).
CC Interacts with RAPGEF2 (PubMed:10873669). Interacts with KLRG1 (By
CC similarity). Forms a ternary complex composed of ADAM10, CADH1 and
CC EPHA4; within the complex, CADH1 is cleaved by ADAM10 which disrupts
CC adherens junctions (By similarity). Interacts with SPEF1 (By
CC similarity). {ECO:0000250|UniProtKB:P09803,
CC ECO:0000250|UniProtKB:P12830, ECO:0000250|UniProtKB:Q9R0T4,
CC ECO:0000269|PubMed:10873669}.
CC -!- SUBCELLULAR LOCATION: Cell junction, adherens junction
CC {ECO:0000250|UniProtKB:P12830}. Cell membrane {ECO:0000250}; Single-
CC pass type I membrane protein {ECO:0000250}. Endosome {ECO:0000250}.
CC Golgi apparatus, trans-Golgi network {ECO:0000250}. Note=Colocalizes
CC with DLGAP5 at sites of cell-cell contact in intestinal epithelial
CC cells. Anchored to actin microfilaments through association with
CC alpha-, beta- and gamma-catenin. Sequential proteolysis induced by
CC apoptosis or calcium influx, results in translocation from sites of
CC cell-cell contact to the cytoplasm. Colocalizes with RAB11A endosomes
CC during its transport from the Golgi apparatus to the plasma membrane
CC (By similarity). {ECO:0000250}.
CC -!- DOMAIN: Three calcium ions are usually bound at the interface of each
CC cadherin domain and rigidify the connections, imparting a strong
CC curvature to the full-length ectodomain. {ECO:0000250}.
CC -!- PTM: During apoptosis or with calcium influx, cleaved by a membrane-
CC bound metalloproteinase (ADAM10), PS1/gamma-secretase and caspase-3 (By
CC similarity). Processing by the metalloproteinase, induced by calcium
CC influx, causes disruption of cell-cell adhesion and the subsequent
CC release of beta-catenin into the cytoplasm (By similarity). The
CC residual membrane-tethered cleavage product is rapidly degraded via an
CC intracellular proteolytic pathway (By similarity). Cleavage by caspase-
CC 3 releases the cytoplasmic tail resulting in disintegration of the
CC actin microfilament system (By similarity). The gamma-secretase-
CC mediated cleavage promotes disassembly of adherens junctions (By
CC similarity). During development of the cochlear organ of Corti,
CC cleavage by ADAM10 at adherens junctions promotes pillar cell
CC separation (By similarity). {ECO:0000250|UniProtKB:P09803,
CC ECO:0000250|UniProtKB:P12830}.
CC -!- PTM: N-glycosylation at Asn-639 is essential for expression, folding
CC and trafficking. Addition of bisecting N-acetylglucosamine by MGAT3
CC modulates its cell membrane location (By similarity). {ECO:0000250,
CC ECO:0000250|UniProtKB:P12830}.
CC -!- PTM: Ubiquitinated by a SCF complex containing SKP2, which requires
CC prior phosphorylation by CK1/CSNK1A1. Ubiquitinated by CBLL1/HAKAI,
CC requires prior phosphorylation at Tyr-757 (By similarity).
CC {ECO:0000250}.
CC -!- PTM: O-glycosylated. O-manosylated by TMTC1, TMTC2, TMTC3 or TMTC4.
CC Thr-287 and Thr-511 are O-mannosylated by TMTC2 or TMTC4 but not TMTC1
CC or TMTC3. {ECO:0000250|UniProtKB:P09803}.
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DR EMBL; AAEX03004114; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAEX03004115; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AAEX03004116; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; NP_001274054.1; NM_001287125.1.
DR AlphaFoldDB; F1PAA9; -.
DR SMR; F1PAA9; -.
DR CORUM; F1PAA9; -.
DR DIP; DIP-61284N; -.
DR IntAct; F1PAA9; 527.
DR MINT; F1PAA9; -.
DR STRING; 9612.ENSCAFP00000030108; -.
DR PaxDb; F1PAA9; -.
DR PRIDE; F1PAA9; -.
DR Ensembl; ENSCAFT00030026548; ENSCAFP00030023171; ENSCAFG00030014198.
DR Ensembl; ENSCAFT00040020426; ENSCAFP00040017722; ENSCAFG00040010861.
DR GeneID; 442858; -.
DR KEGG; cfa:442858; -.
DR CTD; 999; -.
DR eggNOG; KOG3594; Eukaryota.
DR InParanoid; F1PAA9; -.
DR OMA; DFCQKNP; -.
DR OrthoDB; 182239at2759; -.
DR TreeFam; TF316817; -.
DR Reactome; R-CFA-1474228; Degradation of the extracellular matrix.
DR Reactome; R-CFA-216083; Integrin cell surface interactions.
DR Reactome; R-CFA-351906; Apoptotic cleavage of cell adhesion proteins.
DR Reactome; R-CFA-418990; Adherens junctions interactions.
DR Reactome; R-CFA-5626467; RHO GTPases activate IQGAPs.
DR Proteomes; UP000002254; Unplaced.
DR Bgee; ENSCAFG00000020305; Expressed in mucosa of urinary bladder and 41 other tissues.
DR GO; GO:0005912; C:adherens junction; IEA:UniProtKB-SubCell.
DR GO; GO:0043296; C:apical junction complex; IBA:GO_Central.
DR GO; GO:0016342; C:catenin complex; IBA:GO_Central.
DR GO; GO:0005911; C:cell-cell junction; IDA:MGI.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0016600; C:flotillin complex; IBA:GO_Central.
DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0045296; F:cadherin binding; IBA:GO_Central.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0098742; P:cell-cell adhesion via plasma-membrane adhesion molecules; IBA:GO_Central.
DR GO; GO:0007156; P:homophilic cell adhesion via plasma membrane adhesion molecules; IEA:InterPro.
DR GO; GO:0010468; P:regulation of gene expression; ISS:UniProtKB.
DR GO; GO:0007416; P:synapse assembly; IBA:GO_Central.
DR Gene3D; 4.10.900.10; -; 1.
DR InterPro; IPR039808; Cadherin.
DR InterPro; IPR002126; Cadherin-like_dom.
DR InterPro; IPR015919; Cadherin-like_sf.
DR InterPro; IPR020894; Cadherin_CS.
DR InterPro; IPR000233; Cadherin_cytoplasmic-dom.
DR InterPro; IPR014868; Cadherin_pro_dom.
DR InterPro; IPR027397; Catenin-bd_sf.
DR InterPro; IPR030049; CDH1.
DR PANTHER; PTHR24027; PTHR24027; 1.
DR PANTHER; PTHR24027:SF319; PTHR24027:SF319; 1.
DR Pfam; PF00028; Cadherin; 5.
DR Pfam; PF01049; Cadherin_C; 1.
DR Pfam; PF08758; Cadherin_pro; 1.
DR PRINTS; PR00205; CADHERIN.
DR SMART; SM00112; CA; 4.
DR SMART; SM01055; Cadherin_pro; 1.
DR SUPFAM; SSF49313; SSF49313; 6.
DR PROSITE; PS00232; CADHERIN_1; 3.
DR PROSITE; PS50268; CADHERIN_2; 4.
PE 1: Evidence at protein level;
KW Calcium; Cell adhesion; Cell junction; Cell membrane;
KW Cleavage on pair of basic residues; Disulfide bond; Endosome; Glycoprotein;
KW Golgi apparatus; Membrane; Metal-binding; Phosphoprotein;
KW Reference proteome; Repeat; Signal; Transmembrane; Transmembrane helix;
KW Ubl conjugation.
FT SIGNAL 1..26
FT /evidence="ECO:0000255"
FT PROPEP 27..156
FT /evidence="ECO:0000255"
FT /id="PRO_0000423875"
FT CHAIN 157..885
FT /note="Cadherin-1"
FT /id="PRO_0000424033"
FT CHAIN 704..885
FT /note="E-Cad/CTF1"
FT /evidence="ECO:0000255"
FT /id="PRO_0000424034"
FT CHAIN 735..885
FT /note="E-Cad/CTF2"
FT /evidence="ECO:0000255"
FT /id="PRO_0000424035"
FT CHAIN 754..885
FT /note="E-Cad/CTF3"
FT /evidence="ECO:0000255"
FT /id="PRO_0000424036"
FT TOPO_DOM 157..712
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 713..733
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 734..885
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 158..264
FT /note="Cadherin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 265..377
FT /note="Cadherin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 378..488
FT /note="Cadherin 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 489..597
FT /note="Cadherin 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 607..688
FT /note="Cadherin 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT REGION 121..141
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 750..770
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 761..772
FT /note="Required for binding CTNND1 and PSEN1"
FT /evidence="ECO:0000250"
FT REGION 792..811
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 814..885
FT /note="Required for binding alpha, beta and gamma catenins"
FT /evidence="ECO:0000250"
FT BINDING 259
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 259
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 290
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="3"
FT /evidence="ECO:0000250"
FT SITE 753..754
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250"
FT MOD_RES 756
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:P12830"
FT MOD_RES 757
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:P12830"
FT MOD_RES 758
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:P12830"
FT MOD_RES 773
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P12830"
FT MOD_RES 796
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P12830"
FT MOD_RES 841
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09803"
FT MOD_RES 843
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09803"
FT MOD_RES 849
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09803"
FT CARBOHYD 282
FT /note="O-linked (Man...) serine"
FT /evidence="ECO:0000250|UniProtKB:P09803"
FT CARBOHYD 287
FT /note="O-linked (Man...) threonine"
FT /evidence="ECO:0000250|UniProtKB:P09803"
FT CARBOHYD 360
FT /note="O-linked (Man...) threonine"
FT /evidence="ECO:0000250|UniProtKB:P09803"
FT CARBOHYD 472
FT /note="O-linked (Man...) threonine"
FT /evidence="ECO:0000250|UniProtKB:P09803"
FT CARBOHYD 474
FT /note="O-linked (Man...) threonine"
FT /evidence="ECO:0000250|UniProtKB:P09803"
FT CARBOHYD 511
FT /note="O-linked (Man...) threonine"
FT /evidence="ECO:0000250|UniProtKB:P09803"
FT CARBOHYD 560
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 578
FT /note="O-linked (Man...) threonine"
FT /evidence="ECO:0000250|UniProtKB:P09803"
FT CARBOHYD 580
FT /note="O-linked (Man...) threonine"
FT /evidence="ECO:0000250|UniProtKB:P09803"
FT CARBOHYD 582
FT /note="O-linked (Man...) threonine"
FT /evidence="ECO:0000250|UniProtKB:P09803"
FT CARBOHYD 639
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
SQ SEQUENCE 885 AA; 97755 MW; 85644CE9DDF1D241 CRC64;
MGPRYGGAPA LLLPLLLLLQ VSSGLCQEPE PCRPGFGADS YTFTVPRRHL ERGRVLGRVS
FEGCTGLPRT AYVSDDTRFK VGTDGVITVK RPLQLHKPEI SFLVHAWDSS RRKLSTRVRL
KAATHHHHHH HDAPSKTQTE VLTFPSSQHG LRRQKRDWVI PPISCPENEK GPFPKNLVQI
KSNRDKEIKV FYSITGQGAD APPVGVFIIE RETGWLKVTE PLDREQIAKY ILYSHAVSSN
GNAVEDPMEI VITVTDQNDN KPEFTQAVFQ GSVTEGALPG TSVMQVTATD ADDDVNTYNA
AIAYSILTQD PLLPSSMMFT INKDTGVISV LTTGLDREGV PMYTLVVQAA DLQGEGLTTT
ATAVITVTDI NDNPPIFNPT TYQGRVPENK ANVEIAVLKV TDADVPDTPA WRAVYTILNN
NNDQFVVTTD PVTNDGILKT TKGLDFEDKQ QYVLYVTVVN VTPFEVILST STATVTVDVE
DVNEAPIFIP CPKVVSIPED FGVGQEITSY TAEDPDTYME QRITYRIWRD AAGWLEVNPE
SGAIFTRAEL DREDFEHVKN STYEALIIAI DNGSPVATGT GTLLLVLSDV NDNGPIPEPR
NMDFCQKNPQ PHVINIIDPD LPPNTSPFTA ELTHGASVNW TIEYNDPARE SLILKPKKTL
ELGDYKINLK LTDNQNKDQV TTLDVFVCDC EGVVNSCKRT APYAEAGLQV PAILGILGGI
LALLILILLL LLFVRRRRVV KEPLLPPEDD TRDNVYYYDE EGGGEEDQDF DLSQLHRGLD
ARPEVTRNDV APTLLSVPQY RPRPANPDEI GNFIDENLKA ADTDPTAPPY DSLLVFDYEG
SGSEAASLSS LNSSESDQDQ DYDYLNEWGN RFKKLADMYG GGEDD
