DHH
Domain
Desert hedgehog protein N-product
Binds calcium and zinc ions; this stabilizes the protein fold and is essential for protein-protein interactions mediated by this domain.
Desert hedgehog protein
The C-terminal domain regulates the auto-processing and controls the juxtacrine signaling.
Function
Desert hedgehog protein
The C-terminal part of the desert hedgehog protein precursor displays an autoproteolysis and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-length protein into two parts (N-product and C-product) followed by the covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-product (By similarity). Both activities occur in the reticulum endoplasmic (By similarity). Functions in cell-cell mediated juxtacrine signaling (PubMed:24342078). Promotes endothelium integrity (PubMed:33063110). Binds to PTCH1 receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes in endothelial cells (PubMed:33063110). In Schwann cells, controls the development of the peripheral nerve sheath and the transition of mesenchymal cells to form the epithelium-like structure of the perineurial tube (By similarity).
Desert hedgehog protein N-product
The dually lipidated desert hedgehog protein N-product is essential for a variety of patterning events during development (By similarity). Binds to the patched (PTCH1) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes (PubMed:11472839, PubMed:33063110). Required for normal testis development and spermatogenesis, namely for the formation of adult-type Leydig cells and normal development of peritubular cells and seminiferous tubules (By similarity). Activates primary cilia signaling on neighboring valve interstitial cells through a paracrine mechanism (By similarity). May induce motor neurons in lateral neural tube and may have a polarizing activity (PubMed:11472839). Prevents the desert hedgehog protein precursor binding to PTCH1 (PubMed:33063110).
Involvement in disease
46,XY gonadal dysgenesis with minifascicular neuropathy
GDMN
An autosomal recessive disorder characterized by gonadal dysgenesis associated with polyneuropathy. Genital anomalies include the presence of a testis on one side and a streak or an absent gonad at the other, persistence of Muellerian duct structures, and a variable degree of genital ambiguity.
None
The disease may be caused by variants affecting the gene represented in this entry.
46,XY sex reversal 7
SRXY7
A disorder of sex development. Affected individuals have a 46,XY karyotype but present as phenotypically normal females. SRXY7 patients have no functional gonads.
None
The disease may be caused by variants affecting the gene represented in this entry.
Post-translational modifications
Desert hedgehog protein
Partially autoproteolyzed (PubMed:24342078, PubMed:30298535). The C-terminal domain displays an autoproteolysis activity and a cholesterol transferase activity (By similarity). Both activities result in the cleavage of the full-length protein and covalent attachment of a cholesterol moiety to the C-terminal of the newly generated N-terminal fragment (DhhN) (By similarity).
Desert hedgehog protein N-product
N-palmitoylation by HHAT of DhhN is required for desert hedgehog protein N-product multimerization and full activity (By similarity).
Sequence Similarities
Belongs to the hedgehog family.
Cellular localization
- Desert hedgehog protein N-product
- Cell membrane
- Lipid-anchor
- Desert hedgehog protein
- Endoplasmic reticulum membrane
- Golgi apparatus membrane
- Secreted
- Cell membrane
- Co-localizes with HHAT in the ER and Golgi membrane.
Alternative names
Desert hedgehog protein, DHH, HHG-3