Naked cuticle 1 (NKD1) is a human gene that encodes the protein Nkd1, a member of the
Naked cuticle (Nkd)
Naked cuticle (Nkd) is a conserved family of intracellular proteins encoded in most animal genomes. The original mutants were discovered by 1995 Nobel laureates Christiane Nüsslein-Volhard and Eric F. Wieschaus and colleagues in their genetic sc ...
family of proteins that regulate the
Wnt signaling pathway
The Wnt signaling pathways are a group of signal transduction pathways which begin with proteins that pass signals into a cell through cell surface receptors. The name Wnt is a portmanteau created from the names Wingless and Int-1. Wnt signaling p ...
. Insects typically have a single Nkd gene, whereas there are two Nkd genes, Nkd1 and
Nkd2
Naked cuticle 2 (NKD2) is a human gene that encodes the protein Nkd2, one of the Naked cuticle (Nkd) family of proteins that regulate the Wnt signaling pathway. Both Nkd1 and Nkd2 proteins can bind to Dishevelled proteins (DVL1, DVL2, DVL3), bu ...
, in most vertebrates studied to date (zebrafish appear to have additional homologous genes such as Nkd3). Nkd1 binds to the
Dishevelled
Dishevelled (Dsh) is a family of proteins involved in canonical and non-canonical Wnt signalling pathways. Dsh (Dvl in mammals) is a cytoplasmic phosphoprotein that acts directly downstream of frizzled receptors. It takes its name from its initi ...
(Dvl) family of proteins (
DVL1
Segment polarity protein dishevelled homolog DVL-1 is a protein that in humans is encoded by the ''DVL1'' gene.
Function
DVL1, the human homolog of the Drosophila dishevelled gene (dsh) encodes a cytoplasmic phosphoprotein that regulates cell ...
,
DVL2
Segment polarity protein dishevelled homolog DVL-2 is a protein that in humans is encoded by the ''DVL2'' gene.
This gene encodes a member of the dishevelled (dsh) protein family. The vertebrate dsh proteins have approximately 40% amino acid sequ ...
,
DVL3
Segment polarity protein dishevelled homolog DVL-3 is a protein that in humans is encoded by the ''DVL3'' gene.
This gene is a member of a multi-gene family which shares strong similarity with the Drosophila dishevelled gene, dsh. The Drosophila d ...
). Specific truncating NKD1 mutations identified in
DNA mismatch repair
DNA mismatch repair (MMR) is a system for recognizing and repairing erroneous insertion, deletion, and mis-incorporation of nucleobase, bases that can arise during DNA replication and Genetic recombination, recombination, as well as DNA repair, r ...
deficient
colon cancer
Colorectal cancer (CRC), also known as bowel cancer, colon cancer, or rectal cancer, is the development of cancer from the colon or rectum (parts of the large intestine). Signs and symptoms may include blood in the stool, a change in bowel mo ...
that disrupt Nkd1/Dvl binding implicate these mutations as a cause of increased Wnt signaling in approximately 1% of human colon cancer, the majority of which have increased Wnt signaling due to mutations the
adenomatous polyposis coli
Adenomatous polyposis coli (APC) also known as deleted in polyposis 2.5 (DP2.5) is a protein that in humans is encoded by the ''APC'' gene. The APC protein is a negative regulator that controls beta-catenin concentrations and interacts with E-c ...
(APC),
AXIN2
Axin-2 also known as axin-like protein (Axil) or axis inhibition protein 2 (AXIN2) or conductin is a protein that in humans is encoded by the ''AXIN2'' gene.
Function
The Axin-related protein, Axin2, presumably plays an important role in the r ...
, or rarely the
beta-catenin
Catenin beta-1, also known as beta-catenin (β-catenin), is a protein that in humans is encoded by the ''CTNNB1'' gene.
Beta-catenin is a dual function protein, involved in regulation and coordination of cell–cell adhesion and gene transcripti ...
genes.
[Guo J, Cagatay T, Zhou G, Chan CC, Blythe S, Suyama K, Zheng L, Pan K, Qian C, Hamelin R, Thibodeau SN, Klein PS, Wharton KA, Liu W. Mutations in the human naked cuticle homolog NKD1 found in colorectal cancer alter Wnt/Dvl/beta-catenin signaling. PLoS One. 2009 Nov 24;4(11):e7982.{{PMID, 19956716]
Sources
Human proteins