Recombinant Human Desert hedgehog protein (DHH), partial (Active)

Function

The dually lipidated desert hedgehog protein N-product is a morphogen that activates the smoothened signaling pathway, and which is essential for a variety of patterning events during development (By similarity). Acts by binding to the patched receptor (PTCH1 or PTCH2), relieving smoothened (SMO) inhibition by patched, activating the smoothened signaling pathway and transcription of target genes (PubMed:11472839, PubMed:33063110). In the absence of DHH, patched represses the constitutive signaling activity of SMO (By similarity). DHH plays a key role in male gonad development (spermatogenesis) and the formation of Schwann cells (By similarity). 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). 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). May induce motor neurons in lateral neural tube and may have a polarizing activity (PubMed:11472839). Involved in tissue regeneration: secreted from epithelial neuroendocrine cells and elicits a regenerative response from mesenchymal cells (By similarity). Functions in cell-cell mediated juxtacrine signaling (PubMed:24342078). Activates primary cilia signaling on neighboring valve interstitial cells through a paracrine mechanism (By similarity). Promotes endothelium integrity (PubMed:33063110)

Subcellular Location

Secreted; Cell membrane (Lipid-anchor)

Disease Association

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. [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. [The disease may be caused by variants affecting the gene represented in this entry]

Subunit

Multimer

• Tate G. et al. Expression of Sonic hedgehog and its receptor Patched/Smoothened in human cancer cell lines and embryonic organs. — J. Biochem. Mol. Biol. Biophys. (2000)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Drummond I.A. et al. Human desert hedgehog. (JUL-)
• Umehara F. et al. A novel mutation of desert hedgehog in a patient with 46,XY partial gonadal dysgenesis accompanied by minifascicular neuropathy. — Am. J. Hum. Genet. (2000)
• Pathi S. et al. Comparative biological responses to human Sonic, Indian, and Desert hedgehog. — Mech. Dev. (2001)
• Pettigrew C.A. et al. A new role for Hedgehogs in juxtacrine signaling. — Mech. Dev. (2014)
• Callier P. et al. Loss of function mutation in the palmitoyl-transferase HHAT leads to syndromic 46,XY disorder of sex development by impeding Hedgehog protein palmitoylation and signaling. — PLoS Genet. (2014)
• Hollier P.L. et al. Full-length Dhh and N-terminal Shh act as competitive antagonists to regulate angiogenesis and vascular permeability. — Cardiovasc. Res. (2021)