The domain is duplicated in most members of this family. APCDD is directly regulated by the beta-catenin/Tcf complex, and its elevated expression promotes proliferation of colonic epithelial cells in vitro and in vivo (PMID:12384519). APCDD1 has an N-terminal signal-peptide and a C-terminal transmembrane region. The domain is rich in cysteines, there being up to 12 such residues, a structural motif important for interaction between Wnt ligands and their receptors. APCDD1 is expressed in a broad repertoire of cell types, indicating that it may regulate a diverse range of biological processes controlled by Wnt signalling (PMID:20393562).
APCDD1 is directly regulated by the beta-catenin/Tcf complex, and its elevated expression promotes proliferation of colonic epithelial cells in vitro and in vivo [ (PUBMED:12384519) ]. APCDD1 has an N-terminal signal-peptide and a C-terminal transmembrane region. This domain is duplicated in most members of the family. The domain is rich in cysteines, there being up to 12 such residues, a structural motif important for interaction between Wnt ligands and their receptors. APCDD1 is expressed in a broad repertoire of cell types, indicating that it may regulate a diverse range of biological processes controlled by Wnt signalling [ (PUBMED:20393562) ].
Family alignment:
There are 1316 APCDDC domains in 735 proteins in SMART's nrdb database.
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Evolution (species in which this domain is found)
Taxonomic distribution of proteins containing APCDDC domain.
This tree includes only several representative species. The complete taxonomic breakdown of all proteins with APCDDC domain is also avaliable.
Click on the protein counts, or double click on taxonomic names to display all proteins containing APCDDC domain in the selected taxonomic class.
APCDD1 is a novel Wnt inhibitor mutated in hereditary hypotrichosis simplex.
Nature. 2010; 464: 1043-7
Display abstract
Hereditary hypotrichosis simplex is a rare autosomal dominant form of hair losscharacterized by hair follicle miniaturization. Using genetic linkage analysis,we mapped a new locus for the disease to chromosome 18p11.22, and identified amutation (Leu9Arg) in the adenomatosis polyposis down-regulated 1 (APCDD1) genein three families. We show that APCDD1 is a membrane-bound glycoprotein that isabundantly expressed in human hair follicles, and can interact in vitro withWNT3A and LRP5-two essential components of Wnt signalling. Functional studiesshow that APCDD1 inhibits Wnt signalling in a cell-autonomous manner andfunctions upstream of beta-catenin. Moreover, APCDD1 represses activation of Wnt reporters and target genes, and inhibits the biological effects of Wnt signallingduring both the generation of neurons from progenitors in the developing chicknervous system, and axis specification in Xenopus laevis embryos. The mutationLeu9Arg is located in the signal peptide of APCDD1, and perturbs itstranslational processing from the endoplasmic reticulum to the plasma membrane.APCDD1(L9R) probably functions in a dominant-negative manner to inhibit thestability and membrane localization of the wild-type protein. These findingsdescribe a novel inhibitor of the Wnt signalling pathway with an essential rolein human hair growth. As APCDD1 is expressed in a broad repertoire of cell types,our findings indicate that APCDD1 may regulate a diversity of biologicalprocesses controlled by Wnt signalling.
Links (links to other resources describing this domain)
