CADH1_HUMAN » Cadherin-1

CADH1_HUMAN » Cadherin-1
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Topology in Plasma membrane
Topologyextracellular side
cytoplasmic side
CADH1_HUMAN » Cadherin-1 » CAM 120/80;Epithelial cadherin;E-cadherin; Uvomorulin;
Hydrophobic Thickness 32.8 ± 1.4 Å
Tilt Angle 0 ± 0°
ΔGtransfer -53.4 kcal/mol
ΔGfold -28.6 kcal/mol
Links UniProtKB, Pfam, Interpro, iHOP, STRING, HGNC, HMDB
Topology Out
TM Segments 706-731 (706-735)
Pathways

Adherens junction (KEGG)

Apoptosis (Reactome)

Bacterial invasion of epithelial cells (KEGG)

Bladder cancer (KEGG)

Cell adhesion molecules (KEGG)

Cell cycle (KEGG)

Cell cycle - yeast (KEGG)

Cell-Cell communication (Reactome)

Endometrial cancer (KEGG)

Hippo signaling pathway (KEGG)

Immune System (Reactome)

Melanoma (KEGG)

Pathogenic Escherichia coli infection (KEGG)

Pathways in cancer (KEGG)

Progesterone-mediated oocyte maturation (KEGG)

Signal Transduction (Reactome)

Thyroid cancer (KEGG)

Ubiquitin mediated proteolysis (KEGG)

PDB 3ff7 (A/B=155-253), 3ff8 (A/B=155-254), 2o72 (A=155-367), 3l6y (B/D/F=756-773), 2omz (B=156-254), 2omy (B=156-254), 2omv (B=156-255), 2omu (B=156-255), 2omt (B=156-255), 1o6s (B=156-255), 2omx (B=156-258), 3l6x (B=756-773)
OPM none
Complexes

KLRG1:CADH1_HUMAN

CADH1:CADH1_MOUSE

Interactions

ADAM9, Complex: ADAM9:CADH1, PubMed

AJAP1, Complex: CTNB1:CADH1:AJAP1, PubMed

BOC, Complex: BOC:CADH1, PubMed

CADH1, Complex: Homodimer of cadherin-1, PDBID: 3Q2V

CADH3, Complex: CADH1:CADH3, PubMed

CAH9, Complex: CAH9:CADH1, PubMed

CDON, Complex: CADH1:CDON, PubMed

CP17A, Complex: CADH1:CP17A, PubMed

DDR1, Complex: CADH1:DDR1

DDR2, Complex: CADH1:DDR2

DHB3, Complex: CADH1:DHB3

EGFR, Complex: CADH1:EGFR, PubMed

ERBB2, Complex: CADH1:ERBB2, PubMed

FGFR1, Complex: CADH1:FGFR1, PubMed

FRMD5, Complex: CADH1:FRMD5, PubMed

GLT12, Complex: CADH1:GLT12

ITAE, Complex: CADH1:ITB7:ITAE, PubMed

ITB7, Complex: CADH1:ITB7, PubMed

KLRG1, Complex: CADH1:KLRG1, PDBID: 3ff7

MET, Complex: CADH1:MET, PubMed

PTPRF, Complex: PTPRF:CADH1, PubMed

PTPRM, Complex: CADH1:PTPRM, PubMed

PVR, Complex: PVR:CADH1, PubMed

STX17, Complex: CADH1:STX17

Domains

AA: 27-116, PDBID: 1OP4, Subunit A, Seq Identity:27%, Cadherin prodomain like

AA: 159-253, PDBID: 1O6S, Subunit B, Seq Identity:100%, Cadherin domain

AA: 267-366, PDBID: 2O72, Subunit A, Seq Identity:100%, Cadherin domain

AA: 380-478, PDBID: 3Q2V, Subunit A, Seq Identity:72%, Cadherin domain

AA: 491-585, PDBID: 3Q2V, Subunit A, Seq Identity:86%, Cadherin domain

AA: 598-686, PDBID: 3Q2V, Subunit A, Seq Identity:71%, Cadherin domain

AA: 733-879, PDBID: 3L6X, Subunit B, Seq Identity:100%, Cadherin cytoplasmic region

UniProt annotation for CADH1_HUMAN » Cadherin-1
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.

FUNCTION: E-Cad/CTF2 promotes non-amyloidogenic degradation of Abeta precursors. Has a strong inhibitory effect on APP C99 and C83 production.

SUBUNIT: 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 RAB8B (By similarity). Interacts with RAPGEF2 (By similarity). Interacts with DDR1; this stabilizes CDH1 at the cell surface and inhibits its internalization.

TISSUE SPECIFICITY: Non-neural epithelial tissues.

INDUCTION: Expression is repressed by MACROD1.

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.

DISEASE: Hereditary diffuse gastric cancer (HDGC) OMIM: A cancer predisposition syndrome with increased susceptibility to diffuse gastric cancer. Diffuse gastric cancer is a malignant disease characterized by poorly differentiated infiltrating lesions resulting in thickening of the stomach. Malignant tumors start in the stomach, can spread to the esophagus or the small intestine, and can extend through the stomach wall to nearby lymph nodes and organs. It also can metastasize to other parts of the body. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry. Heterozygous CDH1 germline mutations are responsible for familial cases of diffuse gastric cancer. Somatic mutations has also been found in patients with sporadic diffuse gastric cancer and lobular breast cancer.

DISEASE: Endometrial cancer (ENDMC) OMIM: A malignancy of endometrium, the mucous lining of the uterus. Most endometrial cancers are adenocarcinomas, cancers that begin in cells that make and release mucus and other fluids. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

DISEASE: Ovarian cancer (OC) OMIM: The term ovarian cancer defines malignancies originating from ovarian tissue. Although many histologic types of ovarian tumors have been described, epithelial ovarian carcinoma is the most common form. Ovarian cancers are often asymptomatic and the recognized signs and symptoms, even of late-stage disease, are vague. Consequently, most patients are diagnosed with advanced disease. associated with variations affecting the gene represented in this entry.

DISEASE: Breast cancer, lobular (LBC) OMIM: A type of breast cancer that begins in the milk-producing glands (lobules) of the breast. represented in this entry may be involved in disease pathogenesis.

UniProt features for CADH1_HUMAN » Cadherin-1
SIGNAL 1 22 Potential.
PROPEP 23 154 Potential.
CHAIN 155 882 Cadherin-1.
CHAIN 701 882 E-Cad/CTF1.
CHAIN 732 882 E-Cad/CTF2.
CHAIN 751 882 E-Cad/CTF3.
DOMAIN 155 262 Cadherin 1.
DOMAIN 263 375 Cadherin 2.
DOMAIN 376 486 Cadherin 3.
DOMAIN 487 593 Cadherin 4.
DOMAIN 594 697 Cadherin 5.
REGION 758 769 Required for binding CTNND1 and PSEN1.
REGION 811 882 Required for binding alpha, beta and gamma catenins.
SITE 700 701 Cleavage; by a metalloproteinase.
SITE 731 732 Cleavage; by gamma-secretase/PS1.
SITE 750 751 Cleavage; by caspase-3.
DISULFID 163 163 Interchain.
Amino Acid Sequence for CADH1_HUMAN » Cadherin-1
MGPWSRSLSA LLLLLQVSSW LCQEPEPCHP GFDAESYTFT VPRRHLERGR VLGRVNFEDC TGRQRTAYFS LDTRFKVGTD GVITVKRPLR FHNPQIHFLV YAWDSTYRKF STKVTLNTVG HHHRPPPHQA SVSGIQAELL TFPNSSPGLR RQKRDWVIPP ISCPENEKGP FPKNLVQIKS NKDKEGKVFY SITGQGADTP PVGVFIIERE TGWLKVTEPL DRERIATYTL FSHAVSSNGN AVEDPMEILI TVTDQNDNKP EFTQEVFKGS VMEGALPGTS VMEVTATDAD DDVNTYNAAI AYTILSQDPE LPDKNMFTIN RNTGVISVVT TGLDRESFPT YTLVVQAADL QGEGLSTTAT AVITVTDTND NPPIFNPTTY KGQVPENEAN VVITTLKVTD ADAPNTPAWE AVYTILNDDG GQFVVTTNPV NNDGILKTAK GLDFEAKQQY ILHVAVTNVV PFEVSLTTST ATVTVDVLDV NEAPIFVPPE KRVEVSEDFG VGQEITSYTA QEPDTFMEQK ITYRIWRDTA NWLEINPDTG AISTRAELDR EDFEHVKNST YTALIIATDN GSPVATGTGT LLLILSDVND NAPIPEPRTI FFCERNPKPQ VINIIDADLP PNTSPFTAEL THGASANWTI QYNDPTQESI ILKPKMALEV GDYKINLKLM DNQNKDQVTT LEVSVCDCEG AAGVCRKAQP VEAGLQIPAI LGILGGILAL LILILLLLLF LRRRAVVKEP LLPPEDDTRD NVYYYDEEGG GEEDQDFDLS QLHRGLDARP EVTRNDVAPT LMSVPRYLPR PANPDEIGNF IDENLKAADT DPTAPPYDSL LVFDYEGSGS EAASLSSLNS SESDKDQDYD YLNEWGNRFK KLADMYGGGE DD