IHH
Domain
Indian 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.
Function
Indian hedgehog protein
The C-terminal part of the indian 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 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). 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).
Indian hedgehog protein N-product
The dually lipidated indian hedgehog protein N-product is a morphogen which is essential for a variety of patterning events during development. Binds to the patched (PTCH1) receptor, which functions in association with smoothened (SMO), to activate the transcription of target genes (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. In contrast, participates in normal chondrocyte proliferation in a PTHLH-independent pathway (By similarity).
Involvement in disease
Brachydactyly A1
BDA1
A form of brachydactyly. Brachydactyly defines 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. BDA1 inheritance is autosomal dominant.
None
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Indian hedgehog protein N-product
Cholesterylation is required for N-product targeting to lipid rafts and multimerization.
Indian hedgehog protein
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-product (By similarity). The N-product is the active species in both local and long-range signaling, whereas the C-product is degraded in the reticulum endoplasmic (By similarity).
Indian hedgehog protein N-product
N-palmitoylation by HHAT of N-product is required for indian hedgehog protein N-product multimerization and full activity.
Sequence Similarities
Belongs to the hedgehog family.
Tissue Specificity
Expressed in embryonic lung, and in adult kidney and liver.
Cellular localization
- Indian hedgehog protein N-product
- Cell membrane
- Lipid-anchor
- The N-product remains associated with the cell surface.
- Indian hedgehog protein
- Endoplasmic reticulum membrane
- Golgi apparatus membrane
- Secreted
- Co-localizes with HHAT in the ER and Golgi membrane.
Alternative names
Indian hedgehog protein, IHH, HHG-2