KREMEN1

This gene encodes a high-affinity dickkopf homolog 1 (DKK1) transmembrane receptor that functionally cooperates with DKK1 to block wingless (WNT)/beta-catenin signaling. The encoded protein is a component of a membrane complex that modulates canonical WNT signaling through lipoprotein receptor-related protein 6 (LRP6). It contains extracellular kringle, WSC, and CUB domains. Alternatively spliced transcript variants encoding distinct isoforms have been observed for this gene. [provided by RefSeq]

Full Name

kringle containing transmembrane protein 1

Function

Receptor for Dickkopf proteins. Cooperates with DKK1/2 to inhibit Wnt/beta-catenin signaling by promoting the endocytosis of Wnt receptors LRP5 and LRP6. In the absence of DKK1, potentiates Wnt-beta-catenin signaling by maintaining LRP5 or LRP6 at the cell membrane. Can trigger apoptosis in a Wnt-independent manner and this apoptotic activity is inhibited upon binding of the ligand DKK1. Plays a role in limb development; attenuates Wnt signaling in the developing limb to allow normal limb patterning and can also negatively regulate bone formation. Modulates cell fate decisions in the developing cochlea with an inhibitory role in hair cell fate specification.

Biological Process

Apoptotic processISS:UniProtKB
Cell communicationManual Assertion Based On ExperimentTAS:UniProtKB
Limb developmentISS:UniProtKB
Negative regulation of axon regenerationIEA:Ensembl
Negative regulation of canonical Wnt signaling pathwayISS:UniProtKB
Negative regulation of ossificationIEA:Ensembl
Regulation of canonical Wnt signaling pathway1 PublicationNAS:BHF-UCL
Wnt signaling pathwayIEA:UniProtKB-KW

Cellular Location

Cell membrane

Involvement in disease

Ectodermal dysplasia 13, hair/tooth type (ECTD13):
A form of ectodermal dysplasia, a disorder due to abnormal development of two or more ectodermal structures. ECTD13 is an autosomal recessive form characterized by severe oligodontia accompanied by anomalies of hair and skin.

Topology

Extracellular: 21-392
Helical: 393-413
Cytoplasmic: 414-473