IHH_XENLA
ID IHH_XENLA Reviewed; 409 AA.
AC Q91612;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Indian hedgehog protein;
DE Short=IHH;
DE EC=3.1.-.- {ECO:0000250|UniProtKB:Q62226};
DE AltName: Full=Banded hedgehog protein;
DE AltName: Full=X-BHH;
DE Contains:
DE RecName: Full=Indian hedgehog protein N-product;
DE Flags: Precursor;
GN Name=ihh {ECO:0000250|UniProtKB:Q14623}; Synonyms=bhh;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP FUNCTION, AND INDUCTION.
RC TISSUE=Embryo;
RX PubMed=7671800; DOI=10.1242/dev.121.8.2337;
RA Ekker S.C., McGrew L.L., Lai C.-J., Lee J.J., von Kessler D.P., Moon R.T.,
RA Beachy P.A.;
RT "Distinct expression and shared activities of members of the hedgehog gene
RT family of Xenopus laevis.";
RL Development 121:2337-2347(1995).
CC -!- FUNCTION: Signal involved in the early induction and patterning of
CC anterodorsal ectoderm, nervous system and somites. Induces ectopic
CC cement gland formation in embryos.
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).
CC {ECO:0000250|UniProtKB:Q62226}.
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). Signal
CC involved in the early induction and patterning of anterodorsal
CC ectoderm, nervous system and somites. Induces ectopic cement gland
CC formation in embryos (PubMed:7671800). {ECO:0000250|UniProtKB:Q15465,
CC ECO:0000250|UniProtKB:Q62226, ECO:0000269|PubMed:7671800}.
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:0000250|UniProtKB:Q14623}.
CC -!- SUBUNIT: Interacts with BOC and CDON. Interacts with PTCH1 (By
CC similarity). Interacts with glypican GPC3 (By similarity).
CC {ECO:0000250|UniProtKB:P97812, ECO:0000250|UniProtKB:Q14623}.
CC -!- SUBCELLULAR LOCATION: [Indian hedgehog protein N-product]: Cell
CC membrane {ECO:0000250|UniProtKB:Q14623}; 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
CC {ECO:0000250|UniProtKB:Q14623}. Note=Co-localizes with HHAT in the ER
CC and Golgi membrane. {ECO:0000250|UniProtKB:Q15465}.
CC -!- TISSUE SPECIFICITY: Expressed in the marginal zone at early
CC gastrulation. At stage 14, expression begins in the neural plate with
CC expression becoming more prominent in the anterodorsal area at neural
CC tube closure. At this stage, also expressed diffusely in the somitic
CC and pre-somitic mesoderm. By the early tadpole (stages 28-30),
CC expression is widespread throughout anterior structures with highest
CC levels in the otic vesicle, the eye, and the branchial arches.
CC {ECO:0000269|PubMed:7671800}.
CC -!- DEVELOPMENTAL STAGE: First expressed by early gastrulation (stage 8).
CC Expression peaks during neural induction and early organogenesis.
CC {ECO:0000269|PubMed:7671800}.
CC -!- INDUCTION: By activin. {ECO:0000269|PubMed:7671800}.
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:0000250|UniProtKB:Q14623}.
CC -!- PTM: [Indian hedgehog protein N-product]: Cholesterylation is required
CC for N-product targeting to lipid rafts and multimerization.
CC {ECO:0000250|UniProtKB:Q14623}.
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:0000250|UniProtKB:Q14623}.
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; U26404; AAA85165.1; -; mRNA.
DR RefSeq; NP_001079262.1; NM_001085793.1.
DR AlphaFoldDB; Q91612; -.
DR SMR; Q91612; -.
DR MEROPS; C46.003; -.
DR GeneID; 378540; -.
DR KEGG; xla:378540; -.
DR CTD; 378540; -.
DR Xenbase; XB-GENE-865057; ihh.S.
DR OMA; APAVRGC; -.
DR OrthoDB; 1169356at2759; -.
DR Proteomes; UP000186698; Chromosome 9_10S.
DR Bgee; 378540; Expressed in camera-type eye and 7 other tissues.
DR GO; GO:0005615; C:extracellular space; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005113; F:patched binding; ISS:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0007267; P:cell-cell signaling; IEA:InterPro.
DR GO; GO:0016540; P:protein autoprocessing; IEA:InterPro.
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 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.
PE 2: Evidence at transcript level;
KW Autocatalytic cleavage; Calcium; Cell membrane; Developmental protein;
KW Endoplasmic reticulum; Golgi apparatus; Hydrolase; Lipoprotein; Membrane;
KW Metal-binding; Palmitate; Protease; Reference proteome; Secreted; Signal;
KW Zinc.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..409
FT /note="Indian hedgehog protein"
FT /id="PRO_0000013238"
FT CHAIN 24..197
FT /note="Indian hedgehog protein N-product"
FT /id="PRO_0000013239"
FT BINDING 89
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q14623"
FT BINDING 90
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q14623"
FT BINDING 90
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q14623"
FT BINDING 95
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q14623"
FT BINDING 125
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q14623"
FT BINDING 126
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q14623"
FT BINDING 126
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q14623"
FT BINDING 129
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q14623"
FT BINDING 131
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q14623"
FT BINDING 140
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q14623"
FT BINDING 147
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q14623"
FT BINDING 182
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:Q14623"
FT SITE 197..198
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:Q02936"
FT SITE 243
FT /note="Involved in cholesterol transfer"
FT /evidence="ECO:0000250|UniProtKB:Q02936"
FT SITE 267
FT /note="Involved in auto-cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q02936"
FT SITE 270
FT /note="Essential for auto-cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q02936"
FT LIPID 24
FT /note="N-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:Q14623"
FT LIPID 197
FT /note="Cholesterol glycine ester"
FT /evidence="ECO:0000250|UniProtKB:Q02936"
SQ SEQUENCE 409 AA; 45591 MW; 6FB265367FB98627 CRC64;
MQLPKVVLLL CAAALLLSGA VRGCGPGRVV GRRRRPTKLS PLSYKQFSPN VPEKTLGASG
RYEGKISRNS ERFKELTPNY NPDIIFKDEE ITGADRLMTQ RCKDRLNSLA ISVMNQWPGV
KLRVTEGWDE DGHHFEESLH YEGRAVDITT SDRDRNKYGM LARLAVEAGF DWVYYESKAH
IHCSVKSEHS AAAKTGGCFP GEALATLESG EKIPVSQLSP GLRVLAMDNS GRPTYSDFLS
FLDHSPKEEH MFQVIKTQDP HRRLFLTPAH LIFVSDNYST PASEFQAVFA SSVRPGQYIL
VSNVVGLIPA KVRSVNTQTN YGAYAPLTQH GTLVVDDVVV SCFALVQKQR LAQIVYWPLR
VLYNLGIIAG TQPSQQMGIH WYSKALYHLG RLILHGNEFH PLGIVQLES
