chain
-
signal peptide:1-27
-
chain:28-411
-
chain:28-202
checksum
08BE7AD8507C0D9B
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 (PubMed:10465785, PubMed:10631175, PubMed:18582859).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. Associated with the very-low-density lipoprotein (VLDL) particles to function as a circulating morphogen for endothelial cell integrity maintenance (By similarity).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 (PubMed:10465785, PubMed:10631175). Positively regulates PTHLH during endochondral bone formation preventing chondrocyte hypertrophy. In contrast, Ihh is necessary for normal chondrocyte proliferation in a PTHLH-independent pathway (PubMed:10631175).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. Interacts with PTCH1 (By similarity). Interacts with glypican GPC3 (PubMed:23665349).SUBCELLULAR LOCATION The N-product remains associated with the cell surface.SUBCELLULAR LOCATION Co-localizes with HHAT in the ER and Golgi membrane.TISSUE SPECIFICITY In the adult kidney, found in proximal convoluted and proximal straight tubule (PubMed:9079674). Expressed in the developing eye (PubMed:18582859).DEVELOPMENTAL STAGE Detected at 10 dpc in developing gut, at 14.5 days dpc in the cartilage primordium and in the developing urogenital sinus. Expression increases with gestional age in kidney and duodenum, becoming maximal in adulthood.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.DISRUPTION PHENOTYPE Almost half of homozygous embryos mice for IHH died between 10.5 and 12.5 dpc. Also some lethality occurred in late gestation, most of the remaining embryos developed to term but died at birth, due to respiratory failure. Mutants display markedly reduced chondrocyte proliferation, maturation of chondrocytes at inappropriate position, and a failure of osteoblast development in endochondral bones (PubMed:10465785). Ocular anomalies include hypopigmented and misshapen eyes, focal loss of the sclera in the posterior (optic nerve head) region of the eye, and a thin retinal pigment epithelium that is frequently detached from the neural retina (PubMed:18582859).SIMILARITY Belongs to the hedgehog family.SEQUENCE CAUTION Extended N-terminus.
databaseName
UniProt
dbId
92998
description
-
recommendedName: fullName evidence="11"Indian hedgehog protein shortName: IHH ecNumber evidence="4"3.1.-.- alternativeName: HHG-2 component recommendedName: Indian hedgehog protein N-product /component
displayName
UniProt:P97812 Ihh
identifier
P97812
isSequenceChanged
false
keyword
-
Autocatalytic cleavage
-
Calcium
-
Cell membrane
-
Developmental protein
-
Endoplasmic reticulum
-
Glycoprotein
-
Golgi apparatus
-
Hydrolase
-
Lipoprotein
-
Membrane
-
Metal-binding
-
Palmitate
-
Protease
-
Reference proteome
-
Secreted
-
Signal
-
Transferase
-
Zinc
moleculeType
Protein
schemaClass
ReferenceGeneProduct
sequenceLength
411
stId
uniprot:P97812