CADH1_BOVIN
ID CADH1_BOVIN Reviewed; 882 AA.
AC Q6R8F2;
DT 30-MAY-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 25-MAY-2022, entry version 111.
DE RecName: Full=Cadherin-1;
DE AltName: Full=Epithelial cadherin;
DE Short=E-cadherin;
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 Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Hanna C.B., Cox M.L., Golding M.C., Westhusin M.E., Kraemer D.C.;
RT "Sequence of Bos taurus e-cadherin (CDH1) mRNA.";
RL Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases.
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 (By similarity). {ECO:0000250|UniProtKB:P12830}.
CC -!- SUBUNIT: Homodimer; disulfide-linked. Component of an E-cadherin/
CC catenin adhesion complex composed of at least E-cadherin/CDH1, beta-
CC catenin/CTNNB1 or gamma-catenin/JUP, and potentially alpha-
CC catenin/CTNNA1; the complex is located to adherens junctions. Interacts
CC with the TRPV4 and CTNNB1 complex. Interacts with CTNND1. The stable
CC association of CTNNA1 is controversial as CTNNA1 was shown not to bind
CC to F-actin when assembled in the complex. Alternatively, the CTNNA1-
CC containing complex may be linked to F-actin by other proteins such as
CC LIMA1. Interaction with PSEN1, cleaves CDH1 resulting in the
CC disassociation of cadherin-based adherens junctions (CAJs). Interacts
CC with AJAP1 and DLGAP5. Interacts with TBC1D2. Interacts with CAV1.
CC Interacts with PIP5K1C. Interacts with RAB8B. Interacts with DDR1; this
CC stabilizes CDH1 at the cell surface and inhibits its internalization.
CC Interacts with RAPGEF2. Interacts with KLRG1. Forms a ternary complex
CC composed of ADAM10, CADH1 and EPHA4; within the complex, CADH1 is
CC cleaved by ADAM10 which disrupts adherens junctions (By similarity).
CC Interacts with SPEF1 (By similarity). {ECO:0000250|UniProtKB:P09803,
CC ECO:0000250|UniProtKB:P12830, ECO:0000250|UniProtKB:Q9R0T4}.
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 (By similarity). Colocalizes with
CC RAB11A endosomes during its transport from the Golgi apparatus to the
CC plasma membrane (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-637 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-754 (By similarity).
CC {ECO:0000250}.
CC -!- PTM: O-glycosylated. O-manosylated by TMTC1, TMTC2, TMTC3 or TMTC4.
CC Thr-285 and Thr-509 are O-mannosylated by TMTC2 or TMTC4 but not TMTC1
CC or TMTC3. {ECO:0000250|UniProtKB:P09803}.
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DR EMBL; AY508164; AAR91598.1; -; mRNA.
DR RefSeq; NP_001002763.1; NM_001002763.1.
DR AlphaFoldDB; Q6R8F2; -.
DR SMR; Q6R8F2; -.
DR STRING; 9913.ENSBTAP00000021272; -.
DR PaxDb; Q6R8F2; -.
DR PeptideAtlas; Q6R8F2; -.
DR PRIDE; Q6R8F2; -.
DR GeneID; 282637; -.
DR KEGG; bta:282637; -.
DR CTD; 999; -.
DR eggNOG; KOG3594; Eukaryota.
DR InParanoid; Q6R8F2; -.
DR OrthoDB; 182239at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0005912; C:adherens junction; IEA:UniProtKB-SubCell.
DR GO; GO:0030054; C:cell junction; ISS:UniProtKB.
DR GO; GO:0005911; C:cell-cell junction; ISS:UniProtKB.
DR GO; GO:0005768; C:endosome; IEA:UniProtKB-SubCell.
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; ISS:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IEA:InterPro.
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 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 2: Evidence at transcript 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..23
FT /evidence="ECO:0000255"
FT PROPEP 24..154
FT /evidence="ECO:0000255"
FT /id="PRO_0000236222"
FT CHAIN 155..882
FT /note="Cadherin-1"
FT /id="PRO_0000236223"
FT CHAIN 701..882
FT /note="E-Cad/CTF1"
FT /evidence="ECO:0000250"
FT /id="PRO_0000236224"
FT CHAIN 732..882
FT /note="E-Cad/CTF2"
FT /evidence="ECO:0000250"
FT /id="PRO_0000236225"
FT CHAIN 751..882
FT /note="E-Cad/CTF3"
FT /evidence="ECO:0000250"
FT /id="PRO_0000236226"
FT TOPO_DOM 155..709
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 710..730
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 731..882
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 154..262
FT /note="Cadherin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 263..375
FT /note="Cadherin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 376..486
FT /note="Cadherin 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 487..595
FT /note="Cadherin 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT DOMAIN 594..702
FT /note="Cadherin 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00043"
FT REGION 117..137
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 747..767
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 758..769
FT /note="Required for binding CTNND1 and PSEN1"
FT /evidence="ECO:0000250"
FT REGION 811..882
FT /note="Required for binding alpha, beta and gamma catenins"
FT /evidence="ECO:0000250"
FT SITE 700..701
FT /note="Cleavage; by a metalloproteinase"
FT /evidence="ECO:0000250"
FT SITE 731..732
FT /note="Cleavage; by gamma-secretase/PS1"
FT /evidence="ECO:0000250"
FT SITE 750..751
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250"
FT MOD_RES 753
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:P12830"
FT MOD_RES 754
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:P12830"
FT MOD_RES 755
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:P12830"
FT MOD_RES 770
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P12830"
FT MOD_RES 793
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P12830"
FT MOD_RES 838
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09803"
FT MOD_RES 840
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09803"
FT MOD_RES 846
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P09803"
FT CARBOHYD 280
FT /note="O-linked (Man...) serine"
FT /evidence="ECO:0000250|UniProtKB:P09803"
FT CARBOHYD 285
FT /note="O-linked (Man...) threonine"
FT /evidence="ECO:0000250|UniProtKB:P09803"
FT CARBOHYD 358
FT /note="O-linked (Man...) threonine"
FT /evidence="ECO:0000250|UniProtKB:P09803"
FT CARBOHYD 470
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 509
FT /note="O-linked (Man...) threonine"
FT /evidence="ECO:0000250|UniProtKB:P09803"
FT CARBOHYD 558
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 576
FT /note="O-linked (Man...) threonine"
FT /evidence="ECO:0000250|UniProtKB:P09803"
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 637
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 163
FT /note="Interchain"
FT /evidence="ECO:0000250"
SQ SEQUENCE 882 AA; 97938 MW; 0EC5C82ADF7D5F36 CRC64;
MGPWSRSLSA LCCCCRCNPW LCREPEPCIP GFGAESYTFT VPRRNLERGR VLGRVSFEGC
AGLPRTVYVS DDTRFKVHTD GVLTVRRPVH LHRPELSFLV HAWDSTHRKL STKVTLEVSA
HHHHHHSHHD SPSGTQTEVL TFPGPHHGLR RQKRDWVIPP ISCPENEKGP FPKSLVQIKS
NKEKETQVFY SITGQRADTP PVGVFIIERE TGWLKVTQPL DREQIAKYIL FSHAVSSNGQ
AIEEPMEIVI TVTDQNDNKP QFTQEVFKAS ALEGALPGTS VMQVTATDID DEVNTYTAAI
GYTIPAQDPM LPHNKMFTIN KETGVISVLT TGLDRESFPT YTLMVQAADL NGEGLSTTAT
AVITVLDTND NAPRFNPTTY VGSVPENEAN VAITTLTVTD ADDPNTPAWE AVYTVLNDNE
KQFIVVTDPV TNEGTLKTAK GLDFEAKQQY ILYVAVTNVA PFEVTLPTST ATVTVDVIDV
NEAPIFVPPQ KRVEVPEDFG VGLEITSYTA REPDTFMEQK ITYRIWRDTA NWLEINPETG
AISTRAELDR EDVDHVKNST YTALIIATDN GSPPATGTGT LLLFLDDVND NGPVPEPRTM
DFCQRNPEPH IININDPDLP PNTSPFTAEL THGASVNWTI EYNDQERESL ILKPKKTLEL
GDHKINLKLI DNQNKDQVTT LDVHVCDCDG IVSNCRKARP AEAGLQVPAI LGILGGILAF
LILILLLLLL VRRRRVVKEP LLPPEDDTRD NVYYYDEEGG GEEDQDFDLS QLHRGLDARP
EVTRNDVAPT LMSVPQYRPR PANPDEIGNF IDENLKAADS DPTAPPYDSL LVFDYEGSGS
EAATLSSLNS SESDQDQDYD YLNEWGNRFK KLADMYGGGE DD
