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CDH13 (cadherin 13, H-cadherin (heart))

Written2011-03Tamotsu Takeuchi
Department of Pathology, Kochi Medical School, Kohasu, Okou, Nankoku, Kochi 783 8505, Japan

(Note : for Links provided by Atlas : click)

Identity

Alias_symbol (synonym)CDHH
Other aliasT-cadherin
HGNC (Hugo) CDH13
LocusID (NCBI) 1012
Atlas_Id 40018
Location 16q23.3  [Link to chromosome band 16q23]
Location_base_pair Starts at 82660399 and ends at 83830215 bp from pter ( according to hg19-Feb_2009)  [Mapping CDH13.png]
Local_order Telomere-CDH15-CDH13-CDH1-CDH3-CDH16-CDH5-CDH11-CDH8-centrosome.
Fusion genes
(updated 2016)
CDH13 (16q23.3) / MLYCD (16q23.3)IPO8 (12p11.21) / CDH13 (16q23.3)KRAS (12p12.1) / CDH13 (16q23.3)
MIAT (22q12.1) / CDH13 (16q23.3)OSGIN1 (16q23.3) / CDH13 (16q23.3)
Note A cluster of 8 cadherin genes is located on 16q22-24.

DNA/RNA

Note Promoter region of CDH13 is CpG rich and often hypermethylated in various malignant tumors, i.e. breast, lung, colorectal, skin, ovary, chronic myeloid leukemia, and more.
 
  DNA of CDH13 gene composed of 14 coding exons.
Transcription 3828 bp mRNA; 2145 bp open reading frame.
Pseudogene Not yet reported.

Protein

 
  Schematic representation of CDH13 protein. SP: signal peptide sequence, EC: extracellular cadherin repeat, GPI: glycosylphosphatidylinositol anchor.
Description 713 amino acids.
Unlike classical cadherin molecules, CDH13 lacks a transmembrane domain or cytoplasmic region, and is anchored to surface membrane via glycosylphosphatidylinositol anchor. The extracellular domain of CDH13 shows significant homology with other cadherins; however, CDH13 EC1 lacks many amino acids crucial for the adhesive functions.
CDH13 lacks intracellular domain, which is believed to be critical for homophilic adhesion of other classical cadherins.
Expression Heart, skeletal muscle, brain, bone (osteoblast), epidermal basal cell, endothelial cell (tumor vessel, active remodeling vascule).
Controversial experiments and arguments exist for the expression in the liver, hepatocyte.
Localisation Cell surface membrane, lipid raft (cytoplasmic and nuclear localization are also reported).
Function CDH13 is believed to have diverse functions.
1. Adiponectin receptor. CDH13 binds to the hexameric and larger adiponectin, an insulin-sensitizing hormone, which is secreted by adipocytes.
2. Homophilic adhesion. Unlike other classical cadherins, which have the strong homophilic adhesion function, EC1 domain of CDH13 lacks many amino acids crucial for the adhesive functions. Instead CDH13 is thought to form dimers through the non-swapped interface near the EC1-EC2 calcium binding site.
3. Tumor suppressor function. Especially against cancer invasion; however, the exact molecular mechanism which is responsible for inhibiting cancer progression still remains unclear.
4. Angiogenesis. CDH13 facilitates tumor neovascularization. In tumor microenvironment, CDH13 may recruit adiponectin to sequester various growth factors to assist the tumor associated angiogenesis.
Homology CDH1 (approximately 38%).

Mutations

Note Silencing of CDH13 expression is often found in various malignant tumors. Hypermethylation of the promoter region is the major molecular mechanism for loss of CDH13 expression.
Genomic mutation is little reported.

Implicated in

Note
  
Entity Various malignant tumors, i.e. breast, lung, colorectal, skin, ovary and chronic myeloid leukemia
Note Expression of CDH13 is downregulated by the aberrant methylation of the promoter region of CDH13 gene. On the other hand, CDH13 is over-expressed in tumor vascular endothelial cells and thought to support the neoangiogenesis.
  

Bibliography

Zeb1-mediated T-cadherin repression increases the invasive potential of gallbladder cancer.
Adachi Y, Takeuchi T, Nagayama T, Ohtsuki Y, Furihata M.
FEBS Lett. 2009 Jan 22;583(2):430-6. Epub 2008 Dec 29.
PMID 19116147
 
T-cadherin structures reveal a novel adhesive binding mechanism.
Ciatto C, Bahna F, Zampieri N, VanSteenhouse HC, Katsamba PS, Ahlsen G, Harrison OJ, Brasch J, Jin X, Posy S, Vendome J, Ranscht B, Jessell TM, Honig B, Shapiro L.
Nat Struct Mol Biol. 2010 Mar;17(3):339-47. Epub 2010 Feb 28.
PMID 20190755
 
Insights into the low adhesive capacity of human T-cadherin from the NMR structure of Its N-terminal extracellular domain.
Dames SA, Bang E, Haussinger D, Ahrens T, Engel J, Grzesiek S.
J Biol Chem. 2008 Aug 22;283(34):23485-95. Epub 2008 Jun 10.
PMID 18550521
 
T-cadherin is critical for adiponectin-mediated cardioprotection in mice.
Denzel MS, Scimia MC, Zumstein PM, Walsh K, Ruiz-Lozano P, Ranscht B.
J Clin Invest. 2010 Dec 1;120(12):4342-52.
PMID 21041950
 
T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin.
Hug C, Wang J, Ahmad NS, Bogan JS, Tsao TS, Lodish HF.
Proc Natl Acad Sci U S A. 2004 Jul 13;101(28):10308-13. Epub 2004 Jun 21.
PMID 15210937
 
H-cadherin, a novel cadherin with growth inhibitory functions and diminished expression in human breast cancer.
Lee SW.
Nat Med. 1996 Jul;2(7):776-82.
PMID 8673923
 
T-cadherin, a novel cadherin cell adhesion molecule in the nervous system lacks the conserved cytoplasmic region.
Ranscht B, Dours-Zimmermann MT.
Neuron. 1991 Sep;7(3):391-402.
PMID 1654948
 
Cadherin-13, a mediator of calcium-dependent cell-cell adhesion, is silenced by methylation in chronic myeloid leukemia and correlates with pretreatment risk profile and cytogenetic response to interferon alfa.
Roman-Gomez J, Castillejo JA, Jimenez A, Cervantes F, Boque C, Hermosin L, Leon A, Granena A, Colomer D, Heiniger A, Torres A.
J Clin Oncol. 2003 Apr 15;21(8):1472-9.
PMID 12697869
 
The H-cadherin (CDH13) gene is inactivated in human lung cancer.
Sato M, Mori Y, Sakurada A, Fujimura S, Horii A.
Hum Genet. 1998 Jul;103(1):96-101.
PMID 9737784
 
Loss of T-cadherin (CDH13, H-cadherin) expression in cutaneous squamous cell carcinoma.
Takeuchi T, Liang SB, Matsuyoshi N, Zhou S, Miyachi Y, Sonobe H, Ohtsuki Y.
Lab Invest. 2002 Aug;82(8):1023-9.
PMID 12177241
 
Cloning of five human cadherins clarifies characteristic features of cadherin extracellular domain and provides further evidence for two structurally different types of cadherin.
Tanihara H, Sano K, Heimark RL, St John T, Suzuki S.
Cell Adhes Commun. 1994 Apr;2(1):15-26.
PMID 7982033
 
Identification of an atypical lipoprotein-binding protein from human aortic smooth muscle as T-cadherin.
Tkachuk VA, Bochkov VN, Philippova MP, Stambolsky DV, Kuzmenko ES, Sidorova MV, Molokoedov AS, Spirov VG, Resink TJ.
FEBS Lett. 1998 Jan 16;421(3):208-12.
PMID 9468307
 
Aberrant methylation of the CDH13 (H-cadherin) promoter region in colorectal cancers and adenomas.
Toyooka S, Toyooka KO, Harada K, Miyajima K, Makarla P, Sathyanarayana UG, Yin J, Sato F, Shivapurkar N, Meltzer SJ, Gazdar AF.
Cancer Res. 2002 Jun 15;62(12):3382-6.
PMID 12067979
 
Increased expression of H/T-cadherin in tumor-penetrating blood vessels.
Wyder L, Vitaliti A, Schneider H, Hebbard LW, Moritz DR, Wittmer M, Ajmo M, Klemenz R.
Cancer Res. 2000 Sep 1;60(17):4682-8.
PMID 10987267
 

Citation

This paper should be referenced as such :
Takeuchi, T
CDH13 (cadherin 13, H-cadherin (heart))
Atlas Genet Cytogenet Oncol Haematol. 2011;15(10):808-810.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/CDH13ID40018ch16q23.html


Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  Lung: Translocations in Adenocarcinoma


External links

Nomenclature
HGNC (Hugo)CDH13   1753
Cards
AtlasCDH13ID40018ch16q23
Entrez_Gene (NCBI)CDH13  1012  cadherin 13
AliasesCDHH; P105
GeneCards (Weizmann)CDH13
Ensembl hg19 (Hinxton)ENSG00000140945 [Gene_View]  chr16:82660399-83830215 [Contig_View]  CDH13 [Vega]
Ensembl hg38 (Hinxton)ENSG00000140945 [Gene_View]  chr16:82660399-83830215 [Contig_View]  CDH13 [Vega]
ICGC DataPortalENSG00000140945
TCGA cBioPortalCDH13
AceView (NCBI)CDH13
Genatlas (Paris)CDH13
WikiGenes1012
SOURCE (Princeton)CDH13
Genetics Home Reference (NIH)CDH13
Genomic and cartography
GoldenPath hg19 (UCSC)CDH13  -     chr16:82660399-83830215 +  16q23.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)CDH13  -     16q23.3   [Description]    (hg38-Dec_2013)
EnsemblCDH13 - 16q23.3 [CytoView hg19]  CDH13 - 16q23.3 [CytoView hg38]
Mapping of homologs : NCBICDH13 [Mapview hg19]  CDH13 [Mapview hg38]
OMIM601364   
Gene and transcription
Genbank (Entrez)AI802411 AK294277 AK295886 AK298612 AK304592
RefSeq transcript (Entrez)NM_001220488 NM_001220489 NM_001220490 NM_001220491 NM_001220492 NM_001257
RefSeq genomic (Entrez)NC_000016 NC_018927 NT_010498 NW_004929402
Consensus coding sequences : CCDS (NCBI)CDH13
Cluster EST : UnigeneHs.661776 [ NCBI ]
CGAP (NCI)Hs.661776
Alternative Splicing GalleryENSG00000140945
Gene ExpressionCDH13 [ NCBI-GEO ]   CDH13 [ EBI - ARRAY_EXPRESS ]   CDH13 [ SEEK ]   CDH13 [ MEM ]
Gene Expression Viewer (FireBrowse)CDH13 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)1012
GTEX Portal (Tissue expression)CDH13
Protein : pattern, domain, 3D structure
UniProt/SwissProtP55290   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP55290  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP55290
Splice isoforms : SwissVarP55290
PhosPhoSitePlusP55290
Domaine pattern : Prosite (Expaxy)CADHERIN_1 (PS00232)    CADHERIN_2 (PS50268)   
Domains : Interpro (EBI)Cadherin    Cadherin-like    Cadherin_CS    Cadherin_pro_dom   
Domain families : Pfam (Sanger)Cadherin (PF00028)    Cadherin_pro (PF08758)   
Domain families : Pfam (NCBI)pfam00028    pfam08758   
Domain families : Smart (EMBL)CA (SM00112)  Cadherin_pro (SM01055)  
Conserved Domain (NCBI)CDH13
DMDM Disease mutations1012
Blocks (Seattle)CDH13
PDB (SRS)2V37   
PDB (PDBSum)2V37   
PDB (IMB)2V37   
PDB (RSDB)2V37   
Structural Biology KnowledgeBase2V37   
SCOP (Structural Classification of Proteins)2V37   
CATH (Classification of proteins structures)2V37   
SuperfamilyP55290
Human Protein AtlasENSG00000140945
Peptide AtlasP55290
HPRD03219
IPIIPI01013272   IPI00879357   IPI00879347   IPI01015885   IPI00024046   IPI01009466   IPI01018976   IPI00922186   
Protein Interaction databases
DIP (DOE-UCLA)P55290
IntAct (EBI)P55290
FunCoupENSG00000140945
BioGRIDCDH13
STRING (EMBL)CDH13
ZODIACCDH13
Ontologies - Pathways
QuickGOP55290
Ontology : AmiGOmitotic cell cycle  positive regulation of endothelial cell proliferation  positive regulation of cell-matrix adhesion  sprouting angiogenesis  calcium ion binding  extracellular space  cytoplasm  plasma membrane  plasma membrane  caveola  focal adhesion  homophilic cell adhesion via plasma membrane adhesion molecules  negative regulation of cell adhesion  Rho protein signal transduction  negative regulation of cell proliferation  external side of plasma membrane  calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules  Rac protein signal transduction  lamellipodium assembly  regulation of endocytosis  low-density lipoprotein particle binding  positive regulation of cell migration  anchored component of membrane  adherens junction organization  regulation of epidermal growth factor receptor signaling pathway  protein homodimerization activity  neuron projection  endothelial cell migration  keratinocyte proliferation  cadherin binding  positive regulation of transcription from RNA polymerase II promoter  perinuclear region of cytoplasm  positive regulation of smooth muscle cell proliferation  positive regulation of calcium-mediated signaling  positive regulation of positive chemotaxis  localization within membrane  low-density lipoprotein particle mediated signaling  adiponectin binding  extracellular exosome  lipoprotein particle binding  
Ontology : EGO-EBImitotic cell cycle  positive regulation of endothelial cell proliferation  positive regulation of cell-matrix adhesion  sprouting angiogenesis  calcium ion binding  extracellular space  cytoplasm  plasma membrane  plasma membrane  caveola  focal adhesion  homophilic cell adhesion via plasma membrane adhesion molecules  negative regulation of cell adhesion  Rho protein signal transduction  negative regulation of cell proliferation  external side of plasma membrane  calcium-dependent cell-cell adhesion via plasma membrane cell adhesion molecules  Rac protein signal transduction  lamellipodium assembly  regulation of endocytosis  low-density lipoprotein particle binding  positive regulation of cell migration  anchored component of membrane  adherens junction organization  regulation of epidermal growth factor receptor signaling pathway  protein homodimerization activity  neuron projection  endothelial cell migration  keratinocyte proliferation  cadherin binding  positive regulation of transcription from RNA polymerase II promoter  perinuclear region of cytoplasm  positive regulation of smooth muscle cell proliferation  positive regulation of calcium-mediated signaling  positive regulation of positive chemotaxis  localization within membrane  low-density lipoprotein particle mediated signaling  adiponectin binding  extracellular exosome  lipoprotein particle binding  
REACTOMEP55290 [protein]
REACTOME Pathways418990 [pathway]   
NDEx NetworkCDH13
Atlas of Cancer Signalling NetworkCDH13
Wikipedia pathwaysCDH13
Orthology - Evolution
OrthoDB1012
GeneTree (enSembl)ENSG00000140945
Phylogenetic Trees/Animal Genes : TreeFamCDH13
HOVERGENP55290
HOGENOMP55290
Homologs : HomoloGeneCDH13
Homology/Alignments : Family Browser (UCSC)CDH13
Gene fusions - Rearrangements
Fusion : MitelmanCDH13/MLYCD [16q23.3/16q23.3]  
Fusion : MitelmanIPO8/CDH13 [12p11.21/16q23.3]  [t(12;16)(p11;q23)]  
Fusion : MitelmanKRAS/CDH13 [12p12.1/16q23.3]  [t(12;16)(p12;q23)]  
Fusion: TCGAIPO8 12p11.21 CDH13 16q23.3 BRCA
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCDH13 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CDH13
dbVarCDH13
ClinVarCDH13
1000_GenomesCDH13 
Exome Variant ServerCDH13
ExAC (Exome Aggregation Consortium)CDH13 (select the gene name)
Genetic variants : HAPMAP1012
Genomic Variants (DGV)CDH13 [DGVbeta]
DECIPHER (Syndromes)16:82660399-83830215  ENSG00000140945
CONAN: Copy Number AnalysisCDH13 
Mutations
ICGC Data PortalCDH13 
TCGA Data PortalCDH13 
Broad Tumor PortalCDH13
OASIS PortalCDH13 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICCDH13  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDCDH13
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch CDH13
DgiDB (Drug Gene Interaction Database)CDH13
DoCM (Curated mutations)CDH13 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CDH13 (select a term)
intoGenCDH13
NCG5 (London)CDH13
Cancer3DCDH13(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM601364   
Orphanet
MedgenCDH13
Genetic Testing Registry CDH13
NextProtP55290 [Medical]
TSGene1012
GENETestsCDH13
Huge Navigator CDH13 [HugePedia]
snp3D : Map Gene to Disease1012
BioCentury BCIQCDH13
ClinGenCDH13
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD1012
Chemical/Pharm GKB GenePA26287
Clinical trialCDH13
Miscellaneous
canSAR (ICR)CDH13 (select the gene name)
Probes
Litterature
PubMed171 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineCDH13
EVEXCDH13
GoPubMedCDH13
iHOPCDH13
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Wed Apr 12 11:29:21 CEST 2017

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