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Details on Person UniProt:Q14623 IHH

Class:IdReferenceGeneProduct:57202
_chainChangeLogsignal peptide:1-27 added on Sat February 7 2015;chain:28-411 added on Sat February 7 2015;chain:28-202 added on Sat February 7 2015;chain:203-411 added on Sat February 7 2015;chain:203-411 for 57202 removed on Mon August 15 2022
_displayNameUniProt:Q14623 IHH
_timestamp2025-08-15 21:53:34
chainsignal peptide:1-27
chain:28-411
chain:28-202
checksum4DA90C83F5ABF758
commentFUNCTION 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.
descriptionrecommendedName: fullName evidence="14"Indian hedgehog protein shortName: IHH ecNumber evidence="4"3.1.-.- alternativeName: HHG-2 component recommendedName: Indian hedgehog protein N-product /component
geneNameIHH
identifierQ14623
isSequenceChangedFALSE
keyword3D-structure
Autocatalytic cleavage
Calcium
Cell membrane
Developmental protein
Disease variant
Dwarfism
Endoplasmic reticulum
Glycoprotein
Golgi apparatus
Hydrolase
Lipoprotein
Membrane
Metal-binding
Palmitate
Protease
Proteomics identification
Reference proteome
Secreted
Signal
Transferase
Zinc
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
[InstanceEdit:9963647] Weiser, Joel, 2025-08-15
nameIHH
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8878256] ENSEMBL:ENSG00000163501 IHH [Homo sapiens]
secondaryIdentifierIHH_HUMAN
B9EGM5
O43322
Q8N4B9
sequenceLength411
species[Species:48887] Homo sapiens
(referenceEntity)[EntityWithAccessionedSequence:445149] CHOL-N-palmitoyl-L-cysteine-IHH(28-202) [extracellular region] [Homo sapiens]
[EntityWithAccessionedSequence:5358277] 2xHC-IHH(28-411) [endoplasmic reticulum lumen] [Homo sapiens]
[EntityWithAccessionedSequence:5358290] N4glycoAsn-IHH(203-411) [endoplasmic reticulum lumen] [Homo sapiens]
[EntityWithAccessionedSequence:5358293] CHOL-IHH(28-202) [endoplasmic reticulum lumen] [Homo sapiens]
[EntityWithAccessionedSequence:5358308] N4glycoAsn-HC-IHH(28-411) [endoplasmic reticulum lumen] [Homo sapiens]
[EntityWithAccessionedSequence:5362390] N4glycoAsn-2xHC-IHH(28-411) [endoplasmic reticulum lumen] [Homo sapiens]
[EntityWithAccessionedSequence:5362393] ub-N4glycoAsn-IHH(203-411) [cytosol] [Homo sapiens]
[EntityWithAccessionedSequence:5362417] ub-N4glycoAsn-IHH(203-411) [endoplasmic reticulum lumen] [Homo sapiens]
[EntityWithAccessionedSequence:5362425] CHOL-N-palmitoyl-L-cysteine-IHH(28-202) [plasma membrane] [Homo sapiens]
[EntityWithAccessionedSequence:5362445] CHOL-N-palmitoyl-L-cysteine-IHH(28-202) [endoplasmic reticulum lumen] [Homo sapiens]
List all 11 refering instances
(referenceSequence)[ModifiedResidue:445152] glycine cholesterol ester at 202
[ModifiedResidue:445430] N-palmitoyl-L-cysteine at 28
[IntraChainCrosslinkedResidue:5358276] Intra-chain Crosslink via L-cystine (cross-link) at 203 and 347
[InterChainCrosslinkedResidue:5358309] Inter-chain Crosslink via L-cystine (cross-link) at 347 and 53
[ModifiedResidue:5362345] ubiquitinylated lysine at unknown position
[ModifiedResidue:5362389] N4-glycosyl-L-asparagine at 282
(secondReferenceSequence)[InterChainCrosslinkedResidue:5358306] Inter-chain Crosslink via L-cystine (cross-link) at 53 and 347
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No pathways have been reviewed or authored by UniProt:Q14623 IHH (57202)