Recombinant Human Indian hedgehog protein (IHH), partial (Active)

Function

The dually lipidated indian hedgehog protein N-product is a morphogen that activates the smoothened signaling pathway, and which is essential for bone and cartilage 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 (By similarity). In the absence of IHH, patched represses the constitutive signaling activity of SMO (By similarity). Plays a role in morphogenesis of the skeleton by coordinating growth and differentiation of the endochondral skeleton (By similarity). Positively regulates PTHLH expression during endochondral bone formation preventing chondrocyte hypertrophy (By similarity). In contrast, participates in normal chondrocyte proliferation in a PTHLH-independent pathway (By similarity). Involved in the development of retinal pigment epithelium (RPE), photoreceptors and periocular tissues (By similarity). Plays a role in hedgehog paracrine signaling (PubMed:24342078). Associated with the very-low-density lipoprotein (VLDL) particles to function as a circulating morphogen for endothelial cell integrity maintenance (PubMed:20839884)

Subcellular Location

Secreted; Cell membrane (Lipid-anchor)

Disease Association

Brachydactyly A1 (BDA1) : An autosomal dominant form of brachydactyly, a group of inherited malformations characterized by shortening of the digits due to abnormal development of the phalanges and/or the metacarpals. Brachydactyly type A1 is characterized by middle phalanges of all the digits rudimentary or fused with the terminal phalanges. The proximal phalanges of the thumbs and big toes are short. Some BDA1 affected individuals exhibit short stature. [The disease is caused by variants affecting the gene represented in this entry] | Acrocapitofemoral dysplasia (ACFD) : An autosomal recessive disorder characterized by short stature of variable severity with postnatal onset. The most constant radiographic abnormalities are observed in the tubular bones of the hands and in the proximal part of the femur. Cone-shaped epiphyses or a similar epiphyseal configuration with premature epimetaphyseal fusion result in shortening of the skeletal components involved. Cone-shaped epiphyses are also present to a variable extent at the shoulders, knees and ankles. [The disease is caused by variants affecting the gene represented in this entry]

Tissue Specificity

Expressed in embryonic lung, and in adult kidney and liver

Subunit

Interacts with BOC and CDON (PubMed:20519495). Interacts with PTCH1 (PubMed:21537345). Interacts with glypican GPC3 (By similarity)

• 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)
• Mural R.J. et al. PubMed: CI-5GBDQ6B103N1E (JUL-)
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). — Genome Res. (2004)
• Marigo V. et al. Cloning, expression, and chromosomal location of SHH and IHH: two human homologues of the Drosophila segment polarity gene hedgehog. — Genomics (1995)
• Chang D.T. et al. Products, genetic linkage and limb patterning activity of a murine hedgehog gene. — Development (1994)
• Pepinsky R.B. et al. Identification of a palmitic acid-modified form of human Sonic hedgehog. — J. Biol. Chem. (1998)
• Liu T. et al. Human plasma N-glycoproteome analysis by immunoaffinity subtraction, hydrazide chemistry, and mass spectrometry. — J. Proteome Res. (2005)
• Queiroz K.C. et al. Human plasma very low density lipoprotein carries Indian hedgehog. — J. Proteome Res. (2010)