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

2011-03-01   Tamotsu Takeuchi 

Department of Pathology, Kochi Medical School, Kohasu, Okou, Nankoku, Kochi 783 8505, Japan

Identity

HGNC
LOCATION
16q23.3
LOCUSID
ALIAS
CDHH,P105
FUSION GENES

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.
Atlas Image
DNA of CDH13 gene composed of 14 coding exons.

Transcription

3828 bp mRNA; 2145 bp open reading frame.

Pseudogene

Not yet reported.

Proteins

Atlas Image
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

Entity name
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

Pubmed IDLast YearTitleAuthors
191161472009Zeb1-mediated T-cadherin repression increases the invasive potential of gallbladder cancer.Adachi Y et al
201907552010T-cadherin structures reveal a novel adhesive binding mechanism.Ciatto C et al
185505212008Insights into the low adhesive capacity of human T-cadherin from the NMR structure of Its N-terminal extracellular domain.Dames SA et al
210419502010T-cadherin is critical for adiponectin-mediated cardioprotection in mice.Denzel MS et al
152109372004T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin.Hug C et al
86739231996H-cadherin, a novel cadherin with growth inhibitory functions and diminished expression in human breast cancer.Lee SW et al
16549481991T-cadherin, a novel cadherin cell adhesion molecule in the nervous system lacks the conserved cytoplasmic region.Ranscht B et al
126978692003Cadherin-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 et al
97377841998The H-cadherin (CDH13) gene is inactivated in human lung cancer.Sato M et al
121772412002Loss of T-cadherin (CDH13, H-cadherin) expression in cutaneous squamous cell carcinoma.Takeuchi T et al
79820331994Cloning of five human cadherins clarifies characteristic features of cadherin extracellular domain and provides further evidence for two structurally different types of cadherin.Tanihara H et al
94683071998Identification of an atypical lipoprotein-binding protein from human aortic smooth muscle as T-cadherin.Tkachuk VA et al
120679792002Aberrant methylation of the CDH13 (H-cadherin) promoter region in colorectal cancers and adenomas.Toyooka S et al
109872672000Increased expression of H/T-cadherin in tumor-penetrating blood vessels.Wyder L et al

Other Information

Locus ID:

NCBI: 1012
MIM: 601364
HGNC: 1753
Ensembl: ENSG00000140945

Variants:

dbSNP: 1012
ClinVar: 1012
TCGA: ENSG00000140945
COSMIC: CDH13

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000140945ENST00000268613P55290
ENSG00000140945ENST00000428848P55290
ENSG00000140945ENST00000431540P55290
ENSG00000140945ENST00000539548F5H7W7
ENSG00000140945ENST00000562601H3BQH4
ENSG00000140945ENST00000565636P55290
ENSG00000140945ENST00000567109P55290
ENSG00000140945ENST00000567445H3BRL7
ENSG00000140945ENST00000568770H3BTF2
ENSG00000140945ENST00000569144H3BV21

Expression (GTEx)

0
50
100
150

Pathways

PathwaySourceExternal ID
Cell-Cell communicationREACTOMER-HSA-1500931
Cell junction organizationREACTOMER-HSA-446728
Cell-cell junction organizationREACTOMER-HSA-421270
Adherens junctions interactionsREACTOMER-HSA-418990

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
182640962008Multiple loci identified in a genome-wide association study of prostate cancer.448
182640962008Multiple loci identified in a genome-wide association study of prostate cancer.448
183376022008DNA methylation markers and early recurrence in stage I lung cancer.188
195815692009Genome-wide association study of alcohol dependence.165
188390572008Molecular genetics of adult ADHD: converging evidence from genome-wide association and extended pedigree linkage studies.139
188215652008Genome-wide association scan of quantitative traits for attention deficit hyperactivity disorder identifies novel associations and confirms candidate gene associations.133
185198262008Molecular genetics of successful smoking cessation: convergent genome-wide association study results.130
189579412010Genome-wide association scan for five major dimensions of personality.80
221056242012The genetics of attention deficit/hyperactivity disorder in adults, a review.78
183492822008DNA methylation in tumor and matched normal tissues from non-small cell lung cancer patients.71

Citation

Tamotsu Takeuchi

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

Atlas Genet Cytogenet Oncol Haematol. 2011-03-01

Online version: http://atlasgeneticsoncology.org/gene/40018/cdh13