chain
-
signal peptide:1-27
-
chain:28-411
-
chain:28-202
checksum
4DA90C83F5ABF758
comment
-
FUNCTION Plays a role in embryonic morphogenesis; it is involved in the regulation of endochondral skeleton formation, and the development of retinal pigment epithelium (RPE), photoreceptors and periocular tissues (By similarity).FUNCTION 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 endoplasmic reticulum (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).FUNCTION 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).CATALYTIC ACTIVITY glycyl-L-cysteinyl-[protein] + cholesterol + H(+) = [protein]-C-terminal glycyl cholesterol ester + N-terminal L-cysteinyl-[protein]SUBUNIT Multimer.SUBUNIT Interacts with BOC and CDON (PubMed:20519495). Interacts with PTCH1 (PubMed:21537345). Interacts with glypican GPC3 (By similarity).INTERACTION The N-product remains associated with the cell surface.SUBCELLULAR LOCATION Co-localizes with HHAT in the ER and Golgi membrane.TISSUE SPECIFICITY Expressed in embryonic lung, and in adult kidney and liver.DOMAIN Binds calcium and zinc ions; this stabilizes the protein fold and is essential for protein-protein interactions mediated by this domain.PTM Cholesterylation is required for N-product targeting to lipid rafts and multimerization.PTM 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 endoplasmic reticulum (By similarity).PTM N-palmitoylation by HHAT of N-product is required for indian hedgehog protein N-product multimerization and full activity.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the hedgehog family.
databaseName
UniProt
dbId
57202
description
-
recommendedName: fullName evidence="14"Indian hedgehog protein shortName: IHH ecNumber evidence="4"3.1.-.- alternativeName: HHG-2 component recommendedName: Indian hedgehog protein N-product /component
displayName
UniProt:Q14623 IHH
identifier
Q14623
isSequenceChanged
false
keyword
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3D-structure
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Autocatalytic cleavage
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Calcium
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Cell membrane
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Developmental protein
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Disease variant
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Dwarfism
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Endoplasmic reticulum
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Glycoprotein
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Golgi apparatus
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Hydrolase
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Lipoprotein
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Membrane
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Metal-binding
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Palmitate
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Protease
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Proteomics identification
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Reference proteome
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Secreted
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Signal
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Transferase
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Zinc
moleculeType
Protein
schemaClass
ReferenceGeneProduct
secondaryIdentifier
-
IHH_HUMAN
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B9EGM5
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O43322
-
Q8N4B9
sequenceLength
411
stId
uniprot:Q14623