Protein:CDH1 |
Protein Summary |
 Gene summary |
| Gene name: CDH1 | ASpdb.0 ID: 999 | Gene | Gene symbol | CDH1 | Gene ID | 999 |
| Gene name | cadherin 1 |
| Synonyms | Arc-1|BCDS1|CD324|CDHE|ECAD|LCAM|UVO |
| Cytomap | 16q22.1 |
| Type of gene | protein-coding |
| Description | cadherin-1CAM 120/80E-cadherin 1cadherin 1, E-cadherin (epithelial)cadherin 1, type 1, E-cadherin (epithelial)calcium-dependent adhesion protein, epithelialcell-CAM 120/80epididymis secretory sperm binding proteinepithelial cadherinuvomorulin |
| Modification date | 20240416 |
| UniProtAcc | P12830 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | CDH1 | GO:0005886 | plasma membrane | 28301459 |
| Gene | CDH1 | GO:0005912 | adherens junction | 16338932|20086044|24046456|27760340 |
| Gene | CDH1 | GO:0008013 | beta-catenin binding | 17620337 |
| Gene | CDH1 | GO:0009898 | cytoplasmic side of plasma membrane | 20189993 |
| Gene | CDH1 | GO:0015629 | actin cytoskeleton | 16338932 |
| Gene | CDH1 | GO:0016020 | membrane | 16338932 |
| Gene | CDH1 | GO:0016328 | lateral plasma membrane | 16338932|17620337 |
| Gene | CDH1 | GO:0016342 | catenin complex | 18593713 |
| Gene | CDH1 | GO:0016600 | flotillin complex | 24046456 |
| Gene | CDH1 | GO:0030027 | lamellipodium | 24046456 |
| Gene | CDH1 | GO:0030054 | cell junction | 19038973|28169360 |
| Gene | CDH1 | GO:0030864 | cortical actin cytoskeleton | 24046456 |
| Gene | CDH1 | GO:0042307 | positive regulation of protein import into nucleus | 16338932 |
| Gene | CDH1 | GO:0043296 | apical junction complex | 10460003 |
| Gene | CDH1 | GO:0045893 | positive regulation of DNA-templated transcription | 16338932 |
| Gene | CDH1 | GO:0048471 | perinuclear region of cytoplasm | 16338932 |
| Gene | CDH1 | GO:0071285 | cellular response to lithium ion | 12937339 |
| Gene | CDH1 | GO:0071681 | cellular response to indole-3-methanol | 10868478 |
| Gene | CDH1 | GO:0072659 | protein localization to plasma membrane | 17620337 |
| Gene | CDH1 | GO:0098609 | cell-cell adhesion | 16338932|18593713 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P12830-1 | P12830-1_2o72_A.pdb | 2O72 | X-ray | 2.0 | A | 155 | 367 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P12830 | CDH1 | P12830-1 | P12830-2 | 882 | 821 | 380 | 440 | Deletion | none | none | 379 | 379 |
| Multiple sequence alignment of our canonical and alternatively spliced CDH1 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of CDH1 |
| UniProt-id | ENSG | ENST | ENSP |
| P12830-1 | ENSG00000039068.20 | ENST00000261769.10 | ENSP00000261769.4 |
| P12830-2 | ENSG00000039068.20 | ENST00000422392.6 | ENSP00000414946.2 |
| UniProt-id | NM ID | NP ID |
| P12830-1 | NM_004360.4 | NP_004351.1 |
| P12830-2 | NM_001317184.1 | NP_001304113.1 |
| Amino acid sequences of our canonical and alternatively spliced CDH1 |
| accession_id | Protein sequence |
| P12830-1 | MGPWSRSLSALLLLLQVSSWLCQEPEPCHPGFDAESYTFTVPRRHLERGRVLGRVNFEDCTGRQRTAYFSLDTRFKVGTDGVITVKRPLR FHNPQIHFLVYAWDSTYRKFSTKVTLNTVGHHHRPPPHQASVSGIQAELLTFPNSSPGLRRQKRDWVIPPISCPENEKGPFPKNLVQIKS NKDKEGKVFYSITGQGADTPPVGVFIIERETGWLKVTEPLDRERIATYTLFSHAVSSNGNAVEDPMEILITVTDQNDNKPEFTQEVFKGS VMEGALPGTSVMEVTATDADDDVNTYNAAIAYTILSQDPELPDKNMFTINRNTGVISVVTTGLDRESFPTYTLVVQAADLQGEGLSTTAT AVITVTDTNDNPPIFNPTTYKGQVPENEANVVITTLKVTDADAPNTPAWEAVYTILNDDGGQFVVTTNPVNNDGILKTAKGLDFEAKQQY ILHVAVTNVVPFEVSLTTSTATVTVDVLDVNEAPIFVPPEKRVEVSEDFGVGQEITSYTAQEPDTFMEQKITYRIWRDTANWLEINPDTG AISTRAELDREDFEHVKNSTYTALIIATDNGSPVATGTGTLLLILSDVNDNAPIPEPRTIFFCERNPKPQVINIIDADLPPNTSPFTAEL THGASANWTIQYNDPTQESIILKPKMALEVGDYKINLKLMDNQNKDQVTTLEVSVCDCEGAAGVCRKAQPVEAGLQIPAILGILGGILAL LILILLLLLFLRRRAVVKEPLLPPEDDTRDNVYYYDEEGGGEEDQDFDLSQLHRGLDARPEVTRNDVAPTLMSVPRYLPRPANPDEIGNF |
| P12830-2 | MGPWSRSLSALLLLLQVSSWLCQEPEPCHPGFDAESYTFTVPRRHLERGRVLGRVNFEDCTGRQRTAYFSLDTRFKVGTDGVITVKRPLR FHNPQIHFLVYAWDSTYRKFSTKVTLNTVGHHHRPPPHQASVSGIQAELLTFPNSSPGLRRQKRDWVIPPISCPENEKGPFPKNLVQIKS NKDKEGKVFYSITGQGADTPPVGVFIIERETGWLKVTEPLDRERIATYTLFSHAVSSNGNAVEDPMEILITVTDQNDNKPEFTQEVFKGS VMEGALPGTSVMEVTATDADDDVNTYNAAIAYTILSQDPELPDKNMFTINRNTGVISVVTTGLDRESFPTYTLVVQAADLQGEGLSTTAT AVITVTDTNDNPPIFNPTTGLDFEAKQQYILHVAVTNVVPFEVSLTTSTATVTVDVLDVNEAPIFVPPEKRVEVSEDFGVGQEITSYTAQ EPDTFMEQKITYRIWRDTANWLEINPDTGAISTRAELDREDFEHVKNSTYTALIIATDNGSPVATGTGTLLLILSDVNDNAPIPEPRTIF FCERNPKPQVINIIDADLPPNTSPFTAELTHGASANWTIQYNDPTQESIILKPKMALEVGDYKINLKLMDNQNKDQVTTLEVSVCDCEGA AGVCRKAQPVEAGLQIPAILGILGGILALLILILLLLLFLRRRAVVKEPLLPPEDDTRDNVYYYDEEGGGEEDQDFDLSQLHRGLDARPE VTRNDVAPTLMSVPRYLPRPANPDEIGNFIDENLKAADTDPTAPPYDSLLVFDYEGSGSEAASLSSLNSSESDKDQDYDYLNEWGNRFKK |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| CDH1 (go to UniProt):P12830 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P12830 | Topological domain | 155 | 709 | Note=Extracellular;Ontology_term=ECO:0000255;evidence=ECO:0000255 | Type=Deletion;Start=380;End=440 |
| P12830 | Domain | 376 | 486 | Note=Cadherin 3;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU00043 | Type=Deletion;Start=380;End=440 |
Gene Isoform Structures and Expression Levels for CDH1 |
| Gene structures of our canonical and alternative spliced genes of CDH1 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
 |
| Expression levels of gene isoforms across TCGA. |
 |
Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P12830-1 |
| 3D view using mol* of P12830-2 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P12830-1 |
 |
| pLDDT distribution across the protein length of P12830-2 |
 |
Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P12830-1 |
 |
Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P12830-1 | 0.967 | 91 | 1.002 | 300.125 | 0.63 | 0.652 | 0.89 | 0.85 | 0.876 | 0.971 | 0.958 | 152,153,155,156,157,158,160,178,179,180,181,190,23 2,233,234,243,244,245,246,247,248,249 |
| P12830-2 | 0.974 | 86 | 1.009 | 213.346 | 0.587 | 0.675 | 0.93 | 1.024 | 0.82 | 1.248 | 1.435 | 153,154,155,156,158,176,178,179,180,181,190,232,23 3,234,243,244,245,246 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
 |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P12830-1_P12830-1_2o72_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P12830-1_2o72_A_P12830-2.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P12830-1_P12830-2.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P12830-1_vs_P12830-2.png |
 < |
| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P12830-1_vs_P12830-2.png |
 < |
Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to CDH1 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
Related Diseases to CDH1 |
| Previous studies relating to the alternative splicing of CDH1 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| CDH1 | 8033105 | E-cadherin gene mutations provide clues to diffuse type gastric carcinomas. | The calcium-dependent homophilic cell adhesion molecule and candidate suppressor gene, E (epithelial)-cadherin, plays a major role in the organization and integrity of most epithelial tissues. Diffusely growing gastric carcinomas show markedly reduced homophilic cell-to-cell interactions. We speculated that mutations in the E-cadherin gene may be responsible for the scattered phenotype of this type of carcinoma. For that reason we have examined E-cadherin in 26 diffuse type, 20 intestinal type and 7 mixed gastric carcinomas (Laurén's classification) at the DNA, RNA, and protein levels. Reverse transcription polymerase chain reaction and direct sequencing of amplified E-cadherin complementary DNA fragments revealed inframe skipping of either exon 8 or exon 9 in 10 patients with diffuse tumors and an exon 9 deletion in one patient with a mixed carcinoma; both exons encode putative calcium binding domains. These alterations were not seen in nontumorous gastric tissues. Splice site mutations responsible for the exon deletions were identified in six of these patients, eliminating the possibility of alternative splicing mechanisms. Five of these splice site alterations were confirmed as somatic mutations. Non-splice site mutations were observed in three diffuse type tumors, namely a 69-base pair deletion of exon 10 and two point mutations, one of which destroys a putative calcium binding region. Immunohistochemical evaluation showed E-cadherin immunoreactivity in tumors and lymph node metastases of patients expressing abnormal mRNA. The allelic status of the E-cadherin gene was analyzed in one patient, revealing loss of heterozygosity with retention of a mutated E-cadherin allele. Overall, E-cadherin mutations were identified in 50% (13 of 26) of the diffuse type and in 14% (1 of 7) of the mixed carcinomas. In contrast, two silent E-cadherin mutations (not changing the amino acid sequence) were detected in two tumors of the intestinal type. Our study provides strong in vivo evidence that E-cadherin gene mutations may contribute to the development of diffusely growing gastric carcinomas and support a tumor/metastasis suppressor gene hypothesis. | D002872 | Chromosome Deletion |
| CDH1 | 8033105 | E-cadherin gene mutations provide clues to diffuse type gastric carcinomas. | The calcium-dependent homophilic cell adhesion molecule and candidate suppressor gene, E (epithelial)-cadherin, plays a major role in the organization and integrity of most epithelial tissues. Diffusely growing gastric carcinomas show markedly reduced homophilic cell-to-cell interactions. We speculated that mutations in the E-cadherin gene may be responsible for the scattered phenotype of this type of carcinoma. For that reason we have examined E-cadherin in 26 diffuse type, 20 intestinal type and 7 mixed gastric carcinomas (Laurén's classification) at the DNA, RNA, and protein levels. Reverse transcription polymerase chain reaction and direct sequencing of amplified E-cadherin complementary DNA fragments revealed inframe skipping of either exon 8 or exon 9 in 10 patients with diffuse tumors and an exon 9 deletion in one patient with a mixed carcinoma; both exons encode putative calcium binding domains. These alterations were not seen in nontumorous gastric tissues. Splice site mutations responsible for the exon deletions were identified in six of these patients, eliminating the possibility of alternative splicing mechanisms. Five of these splice site alterations were confirmed as somatic mutations. Non-splice site mutations were observed in three diffuse type tumors, namely a 69-base pair deletion of exon 10 and two point mutations, one of which destroys a putative calcium binding region. Immunohistochemical evaluation showed E-cadherin immunoreactivity in tumors and lymph node metastases of patients expressing abnormal mRNA. The allelic status of the E-cadherin gene was analyzed in one patient, revealing loss of heterozygosity with retention of a mutated E-cadherin allele. Overall, E-cadherin mutations were identified in 50% (13 of 26) of the diffuse type and in 14% (1 of 7) of the mixed carcinomas. In contrast, two silent E-cadherin mutations (not changing the amino acid sequence) were detected in two tumors of the intestinal type. Our study provides strong in vivo evidence that E-cadherin gene mutations may contribute to the development of diffusely growing gastric carcinomas and support a tumor/metastasis suppressor gene hypothesis. | D008207 | Lymphatic Metastasis |
| CDH1 | 8033105 | E-cadherin gene mutations provide clues to diffuse type gastric carcinomas. | The calcium-dependent homophilic cell adhesion molecule and candidate suppressor gene, E (epithelial)-cadherin, plays a major role in the organization and integrity of most epithelial tissues. Diffusely growing gastric carcinomas show markedly reduced homophilic cell-to-cell interactions. We speculated that mutations in the E-cadherin gene may be responsible for the scattered phenotype of this type of carcinoma. For that reason we have examined E-cadherin in 26 diffuse type, 20 intestinal type and 7 mixed gastric carcinomas (Laurén's classification) at the DNA, RNA, and protein levels. Reverse transcription polymerase chain reaction and direct sequencing of amplified E-cadherin complementary DNA fragments revealed inframe skipping of either exon 8 or exon 9 in 10 patients with diffuse tumors and an exon 9 deletion in one patient with a mixed carcinoma; both exons encode putative calcium binding domains. These alterations were not seen in nontumorous gastric tissues. Splice site mutations responsible for the exon deletions were identified in six of these patients, eliminating the possibility of alternative splicing mechanisms. Five of these splice site alterations were confirmed as somatic mutations. Non-splice site mutations were observed in three diffuse type tumors, namely a 69-base pair deletion of exon 10 and two point mutations, one of which destroys a putative calcium binding region. Immunohistochemical evaluation showed E-cadherin immunoreactivity in tumors and lymph node metastases of patients expressing abnormal mRNA. The allelic status of the E-cadherin gene was analyzed in one patient, revealing loss of heterozygosity with retention of a mutated E-cadherin allele. Overall, E-cadherin mutations were identified in 50% (13 of 26) of the diffuse type and in 14% (1 of 7) of the mixed carcinomas. In contrast, two silent E-cadherin mutations (not changing the amino acid sequence) were detected in two tumors of the intestinal type. Our study provides strong in vivo evidence that E-cadherin gene mutations may contribute to the development of diffusely growing gastric carcinomas and support a tumor/metastasis suppressor gene hypothesis. | D013274 | Stomach Neoplasms |
| CDH1 | 17909039 | beta-catenin regulates multiple steps of RNA metabolism as revealed by the RNA aptamer in colon cancer cells. | Nuclear beta-catenin forms a transcription complex with TCF-4, which is implicated in colon cancer development and progression. Recently, we and others have shown that beta-catenin could be a regulator of RNA splicing and it also stabilizes the cyclooxygenase-2 (COX-2) mRNA. Here, we further explored the role of beta-catenin in the RNA metabolism in colon cancer cells. To specifically modulate the subcellular functions of beta-catenin, we expressed the RNA aptamer in the form of RNA intramers with unique cellular localizations. The nucleus-expressed RNA intramer proved to be effective in reducing the protein-protein interaction between beta-catenin and TCF-4, thus shown to be a specific regulator of beta-catenin-activated transcription. It could also regulate the alternative splicing of E1A minigene in diverse colon cancer cell lines. In addition, we tested whether beta-catenin could stabilize any other mRNAs and found that cyclin D1 mRNA was also bound and stabilized by beta-catenin. Significantly, the cytoplasm-expressed RNA intramer reverted the beta-catenin-induced COX-2 and cyclin D1 mRNA stabilization. We show here that beta-catenin regulated multiple steps of RNA metabolism in colon cancer cells and might be the protein factor coordinating RNA metabolism. We suggest that the RNA intramers could provide useful ways for inhibiting beta-catenin-mediated transcription and RNA metabolism, which might further enhance the antitumorigenic effects of these molecules in colon cancer cells. | D000230 | Adenocarcinoma |
| CDH1 | 17909039 | beta-catenin regulates multiple steps of RNA metabolism as revealed by the RNA aptamer in colon cancer cells. | Nuclear beta-catenin forms a transcription complex with TCF-4, which is implicated in colon cancer development and progression. Recently, we and others have shown that beta-catenin could be a regulator of RNA splicing and it also stabilizes the cyclooxygenase-2 (COX-2) mRNA. Here, we further explored the role of beta-catenin in the RNA metabolism in colon cancer cells. To specifically modulate the subcellular functions of beta-catenin, we expressed the RNA aptamer in the form of RNA intramers with unique cellular localizations. The nucleus-expressed RNA intramer proved to be effective in reducing the protein-protein interaction between beta-catenin and TCF-4, thus shown to be a specific regulator of beta-catenin-activated transcription. It could also regulate the alternative splicing of E1A minigene in diverse colon cancer cell lines. In addition, we tested whether beta-catenin could stabilize any other mRNAs and found that cyclin D1 mRNA was also bound and stabilized by beta-catenin. Significantly, the cytoplasm-expressed RNA intramer reverted the beta-catenin-induced COX-2 and cyclin D1 mRNA stabilization. We show here that beta-catenin regulated multiple steps of RNA metabolism in colon cancer cells and might be the protein factor coordinating RNA metabolism. We suggest that the RNA intramers could provide useful ways for inhibiting beta-catenin-mediated transcription and RNA metabolism, which might further enhance the antitumorigenic effects of these molecules in colon cancer cells. | D003110 | Colonic Neoplasms |
Clinically important variants in CDH1 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
Copyright 2024-PresentThe University of Texas Health Science Center at Houston (UTHealth Houston) Web File Viewing | Emergency Information |