IHH_HUMAN
ID IHH_HUMAN Reviewed; 411 AA.
AC Q14623; B9EGM5; O43322; Q8N4B9;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2003, sequence version 4.
DT 03-AUG-2022, entry version 218.
DE RecName: Full=Indian hedgehog protein {ECO:0000305};
DE Short=IHH;
DE EC=3.1.-.- {ECO:0000250|UniProtKB:Q62226};
DE AltName: Full=HHG-2;
DE Contains:
DE RecName: Full=Indian hedgehog protein N-product;
DE Flags: Precursor;
GN Name=IHH {ECO:0000312|HGNC:HGNC:5956};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Tate G., Kishimoto K., Mitsuya T.;
RT "Expression of Sonic hedgehog and its receptor Patched/Smoothened in human
RT cancer cell lines and embryonic organs.";
RL J. Biochem. Mol. Biol. Biophys. 4:27-34(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 100-411.
RC TISSUE=Fetal lung;
RX PubMed=7590746; DOI=10.1006/geno.1995.1104;
RA Marigo V., Roberts D.J., Lee S.M.K., Tsukurov O., Levi T., Gastier J.M.,
RA Epstein D.J., Gilbert D.J., Copeland N.G., Seidman C.E., Jenkins N.A.,
RA Seidman J.G., McMahon A.P., Tabin C.;
RT "Cloning, expression, and chromosomal location of SHH and IHH: two human
RT homologues of the Drosophila segment polarity gene hedgehog.";
RL Genomics 28:44-51(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE OF 124-172.
RX PubMed=7720571; DOI=10.1242/dev.120.11.3339;
RA Chang D.T., Lopez A., von Kessler D.P., Chiang C., Simandl B.K., Zhao R.,
RA Seldin M.F., Fallon J.F., Beachy P.A.;
RT "Products, genetic linkage and limb patterning activity of a murine
RT hedgehog gene.";
RL Development 120:3339-3353(1994).
RN [6]
RP PALMITOYLATION AT CYS-28.
RX PubMed=9593755; DOI=10.1074/jbc.273.22.14037;
RA Pepinsky R.B., Zeng C., Wen D., Rayhorn P., Baker D.P., Williams K.P.,
RA Bixler S.A., Ambrose C.M., Garber E.A., Miatkowski K., Taylor F.R.,
RA Wang E.A., Galdes A.;
RT "Identification of a palmitic acid-modified form of human Sonic hedgehog.";
RL J. Biol. Chem. 273:14037-14045(1998).
RN [7]
RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-282.
RC TISSUE=Plasma;
RX PubMed=16335952; DOI=10.1021/pr0502065;
RA Liu T., Qian W.-J., Gritsenko M.A., Camp D.G. II, Monroe M.E., Moore R.J.,
RA Smith R.D.;
RT "Human plasma N-glycoproteome analysis by immunoaffinity subtraction,
RT hydrazide chemistry, and mass spectrometry.";
RL J. Proteome Res. 4:2070-2080(2005).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY, AND FUNCTION.
RX PubMed=20839884; DOI=10.1021/pr100403q;
RA Queiroz K.C., Tio R.A., Zeebregts C.J., Bijlsma M.F., Zijlstra F.,
RA Badlou B., de Vries M., Ferreira C.V., Spek C.A., Peppelenbosch M.P.,
RA Rezaee F.;
RT "Human plasma very low density lipoprotein carries Indian hedgehog.";
RL J. Proteome Res. 9:6052-6059(2010).
RN [9]
RP SUBCELLULAR LOCATION, AND FUNCTION.
RX PubMed=24342078; DOI=10.1016/j.mod.2013.12.002;
RA Pettigrew C.A., Asp E., Emerson C.P. Jr.;
RT "A new role for Hedgehogs in juxtacrine signaling.";
RL Mech. Dev. 131:137-149(2014).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 29-193 IN COMPLEXES WITH CALCIUM
RP IONS; ZINC IONS; BOC AND CDON, DOMAIN, AND INTERACTION WITH BOC AND CDON.
RX PubMed=20519495; DOI=10.1074/jbc.m110.131680;
RA Kavran J.M., Ward M.D., Oladosu O.O., Mulepati S., Leahy D.J.;
RT "All mammalian Hedgehog proteins interact with cell adhesion molecule,
RT down-regulated by oncogenes (CDO) and brother of CDO (BOC) in a conserved
RT manner.";
RL J. Biol. Chem. 285:24584-24590(2010).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (1.44 ANGSTROMS) OF 28-202 OF WILD TYPE AND VARIANTS
RP BDA1 LYS-95; GLU-100 AND LYS-131 IN COMPLEX WITH ZINC IONS, FUNCTION,
RP SUBUNIT, INTERACTION WITH PTCH1, SUBCELLULAR LOCATION, CHOLESTERYLATION,
RP PALMITOYLATION, MUTAGENESIS OF GLU-95, DOMAIN, AND CHARACTERIZATION OF
RP VARIANTS BDA1 LYS-95; ASN-100; GLU-100 AND LYS-131.
RX PubMed=21537345; DOI=10.1038/cr.2011.76;
RA Ma G., Yu J., Xiao Y., Chan D., Gao B., Hu J., He Y., Guo S., Zhou J.,
RA Zhang L., Gao L., Zhang W., Kang Y., Cheah K.S., Feng G., Guo X., Wang Y.,
RA Zhou C.Z., He L.;
RT "Indian hedgehog mutations causing brachydactyly type A1 impair Hedgehog
RT signal transduction at multiple levels.";
RL Cell Res. 21:1343-1357(2011).
RN [12]
RP VARIANTS BDA1 LYS-95; GLU-100 AND LYS-131.
RX PubMed=11455389; DOI=10.1038/ng577;
RA Gao B., Guo J., She C., Shu A., Yang M., Tan Z., Yang X., Guo S., Feng G.,
RA He L.;
RT "Mutations in IHH, encoding Indian hedgehog, cause brachydactyly type A-
RT 1.";
RL Nat. Genet. 28:386-388(2001).
RN [13]
RP VARIANT BDA1 ASN-100.
RX PubMed=12384778; DOI=10.1007/s00439-002-0815-2;
RA McCready M.E., Sweeney E., Fryer A.E., Donnai D., Baig A., Racacho L.,
RA Warman M.L., Hunter A.G.W., Bulman D.E.;
RT "A novel mutation in the IHH gene causes brachydactyly type A1: a 95-year-
RT old mystery resolved.";
RL Hum. Genet. 111:368-375(2002).
RN [14]
RP VARIANTS ACFD LEU-46 AND ALA-190.
RX PubMed=12632327; DOI=10.1086/374318;
RA Hellemans J., Coucke P.J., Giedion A., De Paepe A., Kramer P., Beemer F.,
RA Mortier G.R.;
RT "Homozygous mutations in IHH cause acrocapitofemoral dysplasia, an
RT autosomal recessive disorder with cone-shaped epiphyses in hands and
RT hips.";
RL Am. J. Hum. Genet. 72:1040-1046(2003).
CC -!- FUNCTION: [Indian hedgehog protein]: The C-terminal part of the indian
CC hedgehog protein precursor displays an autoproteolysis and a
CC cholesterol transferase activity (By similarity). Both activities
CC result in the cleavage of the full-length protein into two parts
CC followed by the covalent attachment of a cholesterol moiety to the C-
CC terminal of the newly generated N-product (By similarity). Both
CC activities occur in the reticulum endoplasmic (By similarity). Plays a
CC role in hedgehog paracrine signaling (PubMed:24342078). Associated with
CC the very-low-density lipoprotein (VLDL) particles to function as a
CC circulating morphogen for endothelial cell integrity maintenance
CC (PubMed:20839884). {ECO:0000250|UniProtKB:Q62226,
CC ECO:0000269|PubMed:20839884, ECO:0000269|PubMed:24342078}.
CC -!- FUNCTION: [Indian hedgehog protein N-product]: The dually lipidated
CC indian hedgehog protein N-product is a morphogen which is essential for
CC a variety of patterning events during development. Binds to the patched
CC (PTCH1) receptor, which functions in association with smoothened (SMO),
CC to activate the transcription of target genes (By similarity). Plays a
CC role in morphogenesis of the skeleton by coordinating growth and
CC differentiation of the endochondral skeleton (By similarity).
CC Positively regulates PTHLH expression during endochondral bone
CC formation preventing chondrocyte hypertrophy. In contrast, participates
CC in normal chondrocyte proliferation in a PTHLH-independent pathway (By
CC similarity). {ECO:0000250|UniProtKB:P97812,
CC ECO:0000250|UniProtKB:Q15465, ECO:0000250|UniProtKB:Q62226}.
CC -!- CATALYTIC ACTIVITY: [Indian hedgehog protein]:
CC Reaction=cholesterol + glycyl-L-cysteinyl-[protein] + H(+) = [protein]-
CC C-terminal glycyl cholesterol ester + N-terminal L-cysteinyl-
CC [protein]; Xref=Rhea:RHEA:59504, Rhea:RHEA-COMP:12707, Rhea:RHEA-
CC COMP:15369, Rhea:RHEA-COMP:15374, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16113, ChEBI:CHEBI:65250, ChEBI:CHEBI:143135,
CC ChEBI:CHEBI:143140; Evidence={ECO:0000250|UniProtKB:Q62226};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59505;
CC Evidence={ECO:0000250|UniProtKB:Q62226};
CC -!- SUBUNIT: [Indian hedgehog protein N-product]: Multimer.
CC {ECO:0000269|PubMed:21537345}.
CC -!- SUBUNIT: Interacts with BOC and CDON (PubMed:20519495). Interacts with
CC PTCH1 (PubMed:21537345). Interacts with glypican GPC3 (By similarity).
CC {ECO:0000250|UniProtKB:P97812, ECO:0000269|PubMed:20519495,
CC ECO:0000269|PubMed:21537345}.
CC -!- INTERACTION:
CC Q14623; Q9BWV1: BOC; NbExp=2; IntAct=EBI-3918622, EBI-718555;
CC -!- SUBCELLULAR LOCATION: [Indian hedgehog protein N-product]: Cell
CC membrane {ECO:0000269|PubMed:21537345}; Lipid-anchor
CC {ECO:0000250|UniProtKB:Q62226}. Note=The N-product remains associated
CC with the cell surface. {ECO:0000250|UniProtKB:Q15465}.
CC -!- SUBCELLULAR LOCATION: [Indian hedgehog protein]: Endoplasmic reticulum
CC membrane {ECO:0000250|UniProtKB:Q15465}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q15465}. Secreted {ECO:0000269|PubMed:24342078}.
CC Note=Co-localizes with HHAT in the ER and Golgi membrane.
CC {ECO:0000250|UniProtKB:Q15465}.
CC -!- TISSUE SPECIFICITY: Expressed in embryonic lung, and in adult kidney
CC and liver.
CC -!- DOMAIN: [Indian hedgehog protein N-product]: Binds calcium and zinc
CC ions; this stabilizes the protein fold and is essential for protein-
CC protein interactions mediated by this domain.
CC {ECO:0000269|PubMed:20519495, ECO:0000269|PubMed:21537345}.
CC -!- PTM: [Indian hedgehog protein N-product]: Cholesterylation is required
CC for N-product targeting to lipid rafts and multimerization.
CC {ECO:0000269|PubMed:21537345}.
CC -!- PTM: [Indian hedgehog protein]: The C-terminal domain displays an
CC autoproteolysis activity and a cholesterol transferase activity (By
CC similarity). Both activities result in the cleavage of the full-length
CC protein and covalent attachment of a cholesterol moiety to the C-
CC terminal of the newly generated N-product (By similarity). The N-
CC product is the active species in both local and long-range signaling,
CC whereas the C-product is degraded in the reticulum endoplasmic (By
CC similarity). {ECO:0000250|UniProtKB:Q15465,
CC ECO:0000250|UniProtKB:Q62226}.
CC -!- PTM: [Indian hedgehog protein N-product]: N-palmitoylation by HHAT of
CC N-product is required for indian hedgehog protein N-product
CC multimerization and full activity. {ECO:0000269|PubMed:21537345,
CC ECO:0000269|PubMed:9593755}.
CC -!- DISEASE: Brachydactyly A1 (BDA1) [MIM:112500]: A form of brachydactyly.
CC Brachydactyly defines a group of inherited malformations characterized
CC by shortening of the digits due to abnormal development of the
CC phalanges and/or the metacarpals. Brachydactyly type A1 is
CC characterized by middle phalanges of all the digits rudimentary or
CC fused with the terminal phalanges. The proximal phalanges of the thumbs
CC and big toes are short. BDA1 inheritance is autosomal dominant.
CC {ECO:0000269|PubMed:11455389, ECO:0000269|PubMed:12384778,
CC ECO:0000269|PubMed:21537345}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Acrocapitofemoral dysplasia (ACFD) [MIM:607778]: An autosomal
CC recessive disorder characterized by short stature of variable severity
CC with postnatal onset. The most constant radiographic abnormalities are
CC observed in the tubular bones of the hands and in the proximal part of
CC the femur. Cone-shaped epiphyses or a similar epiphyseal configuration
CC with premature epimetaphyseal fusion result in shortening of the
CC skeletal components involved. Cone-shaped epiphyses are also present to
CC a variable extent at the shoulders, knees and ankles.
CC {ECO:0000269|PubMed:12632327}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the hedgehog family. {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB018076; BAA33523.2; -; Genomic_DNA.
DR EMBL; CH471063; EAW70675.1; -; Genomic_DNA.
DR EMBL; BC034757; AAH34757.2; -; mRNA.
DR EMBL; BC136587; AAI36588.1; -; mRNA.
DR EMBL; BC136588; AAI36589.1; -; mRNA.
DR EMBL; L38517; AAA62178.1; -; mRNA.
DR CCDS; CCDS33380.1; -.
DR RefSeq; NP_002172.2; NM_002181.3.
DR PDB; 3K7G; X-ray; 1.50 A; B=28-202.
DR PDB; 3K7H; X-ray; 1.50 A; B=28-202.
DR PDB; 3K7I; X-ray; 1.44 A; B=28-202.
DR PDB; 3K7J; X-ray; 1.90 A; B=28-202.
DR PDB; 3N1F; X-ray; 1.60 A; A/B=29-193.
DR PDB; 3N1M; X-ray; 1.69 A; B=29-193.
DR PDB; 3N1O; X-ray; 2.55 A; A/B/C=29-193.
DR PDB; 3N1P; X-ray; 2.70 A; B=29-193.
DR PDBsum; 3K7G; -.
DR PDBsum; 3K7H; -.
DR PDBsum; 3K7I; -.
DR PDBsum; 3K7J; -.
DR PDBsum; 3N1F; -.
DR PDBsum; 3N1M; -.
DR PDBsum; 3N1O; -.
DR PDBsum; 3N1P; -.
DR AlphaFoldDB; Q14623; -.
DR SMR; Q14623; -.
DR BioGRID; 109765; 10.
DR IntAct; Q14623; 4.
DR STRING; 9606.ENSP00000295731; -.
DR MEROPS; C46.003; -.
DR GlyGen; Q14623; 1 site.
DR iPTMnet; Q14623; -.
DR PhosphoSitePlus; Q14623; -.
DR BioMuta; IHH; -.
DR DMDM; 33112634; -.
DR MassIVE; Q14623; -.
DR MaxQB; Q14623; -.
DR PaxDb; Q14623; -.
DR PeptideAtlas; Q14623; -.
DR PRIDE; Q14623; -.
DR ProteomicsDB; 60073; -.
DR Antibodypedia; 3977; 529 antibodies from 37 providers.
DR DNASU; 3549; -.
DR Ensembl; ENST00000295731.7; ENSP00000295731.5; ENSG00000163501.7.
DR GeneID; 3549; -.
DR KEGG; hsa:3549; -.
DR MANE-Select; ENST00000295731.7; ENSP00000295731.5; NM_002181.4; NP_002172.2.
DR UCSC; uc002vjo.3; human.
DR CTD; 3549; -.
DR DisGeNET; 3549; -.
DR GeneCards; IHH; -.
DR HGNC; HGNC:5956; IHH.
DR HPA; ENSG00000163501; Tissue enhanced (endometrium, intestine, stomach).
DR MalaCards; IHH; -.
DR MIM; 112500; phenotype.
DR MIM; 600726; gene.
DR MIM; 607778; phenotype.
DR neXtProt; NX_Q14623; -.
DR OpenTargets; ENSG00000163501; -.
DR Orphanet; 63446; Acrocapitofemoral dysplasia.
DR Orphanet; 93388; Brachydactyly type A1.
DR PharmGKB; PA29769; -.
DR VEuPathDB; HostDB:ENSG00000163501; -.
DR eggNOG; KOG3638; Eukaryota.
DR GeneTree; ENSGT00940000159207; -.
DR HOGENOM; CLU_034686_0_0_1; -.
DR InParanoid; Q14623; -.
DR OMA; APAVRGC; -.
DR OrthoDB; 1169356at2759; -.
DR PhylomeDB; Q14623; -.
DR TreeFam; TF106458; -.
DR PathwayCommons; Q14623; -.
DR Reactome; R-HSA-373080; Class B/2 (Secretin family receptors).
DR Reactome; R-HSA-5358346; Hedgehog ligand biogenesis.
DR Reactome; R-HSA-5362798; Release of Hh-Np from the secreting cell.
DR Reactome; R-HSA-5632681; Ligand-receptor interactions.
DR Reactome; R-HSA-5632684; Hedgehog 'on' state.
DR Reactome; R-HSA-5635838; Activation of SMO.
DR Reactome; R-HSA-5658034; HHAT G278V doesn't palmitoylate Hh-Np.
DR Reactome; R-HSA-8941284; RUNX2 regulates chondrocyte maturation.
DR SignaLink; Q14623; -.
DR SIGNOR; Q14623; -.
DR BioGRID-ORCS; 3549; 6 hits in 1066 CRISPR screens.
DR EvolutionaryTrace; Q14623; -.
DR GeneWiki; IHH_(protein); -.
DR GenomeRNAi; 3549; -.
DR Pharos; Q14623; Tbio.
DR PRO; PR:Q14623; -.
DR Proteomes; UP000005640; Chromosome 2.
DR RNAct; Q14623; protein.
DR Bgee; ENSG00000163501; Expressed in mucosa of transverse colon and 70 other tissues.
DR Genevisible; Q14623; HS.
DR GO; GO:0031012; C:extracellular matrix; IEA:Ensembl.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0005509; F:calcium ion binding; IDA:UniProtKB.
DR GO; GO:0005113; F:patched binding; IDA:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0045453; P:bone resorption; IEA:Ensembl.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IEA:Ensembl.
DR GO; GO:0060220; P:camera-type eye photoreceptor cell fate commitment; IEA:Ensembl.
DR GO; GO:0051216; P:cartilage development; IMP:AgBase.
DR GO; GO:0001708; P:cell fate specification; IBA:GO_Central.
DR GO; GO:0048469; P:cell maturation; IEA:Ensembl.
DR GO; GO:0007267; P:cell-cell signaling; IEA:InterPro.
DR GO; GO:0003413; P:chondrocyte differentiation involved in endochondral bone morphogenesis; IEA:Ensembl.
DR GO; GO:0035988; P:chondrocyte proliferation; IEA:Ensembl.
DR GO; GO:0048596; P:embryonic camera-type eye morphogenesis; IEA:Ensembl.
DR GO; GO:0048557; P:embryonic digestive tract morphogenesis; IEA:Ensembl.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IMP:AgBase.
DR GO; GO:0009880; P:embryonic pattern specification; IEA:Ensembl.
DR GO; GO:0072498; P:embryonic skeletal joint development; IEA:Ensembl.
DR GO; GO:0003382; P:epithelial cell morphogenesis; IEA:Ensembl.
DR GO; GO:0090136; P:epithelial cell-cell adhesion; IEA:Ensembl.
DR GO; GO:0060323; P:head morphogenesis; IEA:Ensembl.
DR GO; GO:0001947; P:heart looping; ISS:BHF-UCL.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0016539; P:intein-mediated protein splicing; IEA:InterPro.
DR GO; GO:0097421; P:liver regeneration; IEA:Ensembl.
DR GO; GO:0060135; P:maternal process involved in female pregnancy; IEA:Ensembl.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0046639; P:negative regulation of alpha-beta T cell differentiation; ISS:BHF-UCL.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl.
DR GO; GO:0032331; P:negative regulation of chondrocyte differentiation; IEA:Ensembl.
DR GO; GO:0048074; P:negative regulation of eye pigmentation; IEA:Ensembl.
DR GO; GO:0033088; P:negative regulation of immature T cell proliferation in thymus; ISS:BHF-UCL.
DR GO; GO:0033085; P:negative regulation of T cell differentiation in thymus; ISS:BHF-UCL.
DR GO; GO:0048666; P:neuron development; IEA:Ensembl.
DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0031016; P:pancreas development; IEA:Ensembl.
DR GO; GO:0046638; P:positive regulation of alpha-beta T cell differentiation; ISS:BHF-UCL.
DR GO; GO:0032967; P:positive regulation of collagen biosynthetic process; IEA:Ensembl.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0002053; P:positive regulation of mesenchymal cell proliferation; IEA:Ensembl.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; ISS:BHF-UCL.
DR GO; GO:0033089; P:positive regulation of T cell differentiation in thymus; ISS:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
DR GO; GO:0016540; P:protein autoprocessing; IEA:InterPro.
DR GO; GO:0006029; P:proteoglycan metabolic process; IEA:Ensembl.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0040008; P:regulation of growth; IEA:Ensembl.
DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR GO; GO:0009612; P:response to mechanical stimulus; IEA:Ensembl.
DR GO; GO:0003406; P:retinal pigment epithelium development; IEA:Ensembl.
DR GO; GO:0001501; P:skeletal system development; IMP:UniProtKB.
DR GO; GO:0048745; P:smooth muscle tissue development; IEA:Ensembl.
DR GO; GO:0007224; P:smoothened signaling pathway; IDA:UniProtKB.
DR GO; GO:0061053; P:somite development; ISS:BHF-UCL.
DR GO; GO:0030704; P:vitelline membrane formation; IEA:Ensembl.
DR Gene3D; 3.30.1380.10; -; 1.
DR InterPro; IPR001657; Hedgehog.
DR InterPro; IPR001767; Hedgehog_Hint.
DR InterPro; IPR009045; Hedgehog_sig/DD-Pept_Zn-bd_sf.
DR InterPro; IPR000320; Hedgehog_signalling_dom.
DR InterPro; IPR003586; Hint_dom_C.
DR InterPro; IPR003587; Hint_dom_N.
DR InterPro; IPR036844; Hint_dom_sf.
DR InterPro; IPR033385; IHH.
DR InterPro; IPR006141; Intein_N.
DR PANTHER; PTHR11889:SF39; PTHR11889:SF39; 1.
DR Pfam; PF01085; HH_signal; 1.
DR Pfam; PF01079; Hint; 1.
DR PIRSF; PIRSF009400; Peptidase_C46; 1.
DR PRINTS; PR00632; SONICHHOG.
DR SMART; SM00305; HintC; 1.
DR SMART; SM00306; HintN; 1.
DR SUPFAM; SSF51294; SSF51294; 1.
DR SUPFAM; SSF55166; SSF55166; 1.
DR PROSITE; PS50817; INTEIN_N_TER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Autocatalytic cleavage; Calcium; Cell membrane;
KW Developmental protein; Disease variant; Endoplasmic reticulum;
KW Glycoprotein; Golgi apparatus; Hydrolase; Lipoprotein; Membrane;
KW Metal-binding; Palmitate; Protease; Reference proteome; Secreted; Signal;
KW Zinc.
FT SIGNAL 1..27
FT /evidence="ECO:0000305"
FT CHAIN 28..411
FT /note="Indian hedgehog protein"
FT /id="PRO_0000013229"
FT CHAIN 28..202
FT /note="Indian hedgehog protein N-product"
FT /id="PRO_0000013230"
FT BINDING 94
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:20519495"
FT BINDING 95
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:20519495"
FT BINDING 95
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:20519495"
FT BINDING 100
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:20519495"
FT BINDING 130
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:20519495"
FT BINDING 131
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:20519495"
FT BINDING 131
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:20519495"
FT BINDING 134
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:20519495"
FT BINDING 136
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:20519495"
FT BINDING 145
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:20519495,
FT ECO:0000269|PubMed:21537345"
FT BINDING 152
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:20519495,
FT ECO:0000269|PubMed:21537345"
FT BINDING 187
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:20519495,
FT ECO:0000269|PubMed:21537345"
FT SITE 202..203
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:Q02936"
FT SITE 248
FT /note="Involved in cholesterol transfer"
FT /evidence="ECO:0000250|UniProtKB:Q02936"
FT SITE 272
FT /note="Involved in auto-cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q02936"
FT SITE 275
FT /note="Essential for auto-cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q02936"
FT LIPID 28
FT /note="N-palmitoyl cysteine"
FT /evidence="ECO:0000305|PubMed:9593755"
FT LIPID 202
FT /note="Cholesterol glycine ester"
FT /evidence="ECO:0000250|UniProtKB:Q02936"
FT CARBOHYD 282
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000269|PubMed:16335952"
FT VARIANT 46
FT /note="P -> L (in ACFD; dbSNP:rs121917856)"
FT /evidence="ECO:0000269|PubMed:12632327"
FT /id="VAR_015981"
FT VARIANT 95
FT /note="E -> K (in BDA1; decreases the stability of the
FT indian hedgehog protein N-product; dbSNP:rs121917852)"
FT /evidence="ECO:0000269|PubMed:11455389,
FT ECO:0000269|PubMed:21537345"
FT /id="VAR_015982"
FT VARIANT 100
FT /note="D -> E (in BDA1; decreases the stability of the
FT indian hedgehog protein N-product; dbSNP:rs121917854)"
FT /evidence="ECO:0000269|PubMed:11455389,
FT ECO:0000269|PubMed:21537345"
FT /id="VAR_015983"
FT VARIANT 100
FT /note="D -> N (in BDA1; decreases the stability of the
FT indian hedgehog protein N-product; dbSNP:rs121917855)"
FT /evidence="ECO:0000269|PubMed:12384778,
FT ECO:0000269|PubMed:21537345"
FT /id="VAR_015984"
FT VARIANT 131
FT /note="E -> K (in BDA1; no effect on the stability of the
FT indian hedgehog protein N-product; dbSNP:rs121917853)"
FT /evidence="ECO:0000269|PubMed:11455389,
FT ECO:0000269|PubMed:21537345"
FT /id="VAR_015985"
FT VARIANT 190
FT /note="V -> A (in ACFD; dbSNP:rs121917857)"
FT /evidence="ECO:0000269|PubMed:12632327"
FT /id="VAR_015986"
FT MUTAGEN 95
FT /note="E->G: Increases the lysosomal degradation of the
FT indian hedgehog protein N-product."
FT /evidence="ECO:0000269|PubMed:21537345"
FT CONFLICT 100
FT /note="D -> R (in Ref. 4; AAA62178)"
FT /evidence="ECO:0000305"
FT CONFLICT 246
FT /note="F -> L (in Ref. 1; BAA33523)"
FT /evidence="ECO:0000305"
FT CONFLICT 309
FT /note="V -> A (in Ref. 1; BAA33523)"
FT /evidence="ECO:0000305"
FT STRAND 52..56
FT /evidence="ECO:0007829|PDB:3K7I"
FT TURN 61..64
FT /evidence="ECO:0007829|PDB:3K7I"
FT STRAND 73..75
FT /evidence="ECO:0007829|PDB:3N1P"
FT HELIX 76..80
FT /evidence="ECO:0007829|PDB:3K7I"
FT STRAND 89..91
FT /evidence="ECO:0007829|PDB:3K7I"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:3K7I"
FT HELIX 99..101
FT /evidence="ECO:0007829|PDB:3K7I"
FT HELIX 105..121
FT /evidence="ECO:0007829|PDB:3K7I"
FT STRAND 127..131
FT /evidence="ECO:0007829|PDB:3K7I"
FT HELIX 144..147
FT /evidence="ECO:0007829|PDB:3K7I"
FT STRAND 150..155
FT /evidence="ECO:0007829|PDB:3K7I"
FT HELIX 160..162
FT /evidence="ECO:0007829|PDB:3K7I"
FT HELIX 163..172
FT /evidence="ECO:0007829|PDB:3K7I"
FT STRAND 176..182
FT /evidence="ECO:0007829|PDB:3K7I"
FT STRAND 185..189
FT /evidence="ECO:0007829|PDB:3K7I"
FT STRAND 193..195
FT /evidence="ECO:0007829|PDB:3K7I"
SQ SEQUENCE 411 AA; 45251 MW; 4DA90C83F5ABF758 CRC64;
MSPARLRPRL HFCLVLLLLL VVPAAWGCGP GRVVGSRRRP PRKLVPLAYK QFSPNVPEKT
LGASGRYEGK IARSSERFKE LTPNYNPDII FKDEENTGAD RLMTQRCKDR LNSLAISVMN
QWPGVKLRVT EGWDEDGHHS EESLHYEGRA VDITTSDRDR NKYGLLARLA VEAGFDWVYY
ESKAHVHCSV KSEHSAAAKT GGCFPAGAQV RLESGARVAL SAVRPGDRVL AMGEDGSPTF
SDVLIFLDRE PHRLRAFQVI ETQDPPRRLA LTPAHLLFTA DNHTEPAARF RATFASHVQP
GQYVLVAGVP GLQPARVAAV STHVALGAYA PLTKHGTLVV EDVVASCFAA VADHHLAQLA
FWPLRLFHSL AWGSWTPGEG VHWYPQLLYR LGRLLLEEGS FHPLGMSGAG S
