IHH_DANRE
ID IHH_DANRE Reviewed; 412 AA.
AC Q98862;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 144.
DE RecName: Full=Indian hedgehog B protein;
DE Short=IHHB;
DE EC=3.1.-.- {ECO:0000250|UniProtKB:Q62226};
DE AltName: Full=Echidna hedgehog protein {ECO:0000303|PubMed:8684485};
DE Short=EHH;
DE Contains:
DE RecName: Full=Indian hedgehog B protein N-product;
DE Flags: Precursor;
GN Name=ihhb; Synonyms=ehh, ihh;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=8684485; DOI=10.1038/382452a0;
RA Currie P.D., Ingham P.W.;
RT "Induction of a specific muscle cell type by a hedgehog-like protein in
RT zebrafish.";
RL Nature 382:452-455(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 113-170.
RC TISSUE=Muscle;
RX PubMed=8917540; DOI=10.1073/pnas.93.23.13036;
RA Zardoya R., Abouheif E., Meyer A.;
RT "Evolutionary analyses of hedgehog and Hoxd-10 genes in fish species
RT closely related to the zebrafish.";
RL Proc. Natl. Acad. Sci. U.S.A. 93:13036-13041(1996).
CC -!- FUNCTION: [Indian hedgehog B protein]: The C-terminal part of the
CC indian 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 B protein]: The dually lipidated indian
CC hedgehog protein N-product is a morphogen which is essential for a
CC 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). In the
CC notochord, induces somite patterning and muscle pioneer differentiation
CC (PubMed:8684485). {ECO:0000250|UniProtKB:Q15465,
CC ECO:0000250|UniProtKB:Q62226, ECO:0000269|PubMed:8684485}.
CC -!- CATALYTIC ACTIVITY: [Indian hedgehog B 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 B 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 B 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 B protein]: Endoplasmic
CC reticulum membrane {ECO:0000250|UniProtKB:Q15465}. Golgi apparatus
CC membrane {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 exclusively in the notochord.
CC {ECO:0000269|PubMed:8684485}.
CC -!- DEVELOPMENTAL STAGE: First detectable at the mid-gastrula stage.
CC Disappears at the end of the somitogenesis.
CC {ECO:0000269|PubMed:8684485}.
CC -!- DOMAIN: [Indian hedgehog B 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 B protein N-product]: Cholesterylation is
CC required for N-product targeting to lipid rafts and multimerization.
CC {ECO:0000250|UniProtKB:Q14623}.
CC -!- PTM: [Indian hedgehog B 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 B 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; Y08426; CAA69702.1; -; mRNA.
DR RefSeq; NP_571163.1; NM_131088.1.
DR AlphaFoldDB; Q98862; -.
DR SMR; Q98862; -.
DR STRING; 7955.ENSDARP00000076199; -.
DR PaxDb; Q98862; -.
DR GeneID; 30299; -.
DR KEGG; dre:30299; -.
DR CTD; 30299; -.
DR ZFIN; ZDB-GENE-980526-135; ihhb.
DR eggNOG; KOG3638; Eukaryota.
DR InParanoid; Q98862; -.
DR OrthoDB; 1169356at2759; -.
DR PhylomeDB; Q98862; -.
DR SignaLink; Q98862; -.
DR PRO; PR:Q98862; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Unplaced.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central.
DR GO; GO:0005113; F:patched binding; ISS:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0001708; P:cell fate specification; IBA:GO_Central.
DR GO; GO:0007267; P:cell-cell signaling; IEA:InterPro.
DR GO; GO:0016539; P:intein-mediated protein splicing; IEA:InterPro.
DR GO; GO:0048709; P:oligodendrocyte differentiation; IMP:ZFIN.
DR GO; GO:0016540; P:protein autoprocessing; IEA:InterPro.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0070445; P:regulation of oligodendrocyte progenitor proliferation; IMP:ZFIN.
DR GO; GO:0007224; P:smoothened signaling pathway; IBA:GO_Central.
DR GO; GO:0055002; P:striated muscle cell development; IGI:ZFIN.
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 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..412
FT /note="Indian hedgehog B protein"
FT /id="PRO_0000013241"
FT CHAIN 24..197
FT /note="Indian hedgehog B protein N-product"
FT /id="PRO_0000013242"
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 246
FT /note="Involved in cholesterol transfer"
FT /evidence="ECO:0000250|UniProtKB:Q02936"
FT SITE 269
FT /note="Involved in auto-cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q02936"
FT SITE 272
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"
FT CONFLICT 121
FT /note="R -> K (in Ref. 2)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 412 AA; 45746 MW; 21D43F052A278CA1 CRC64;
MRLSTAAALL TGFILAFSPA YDGCGPGRGY GKRRTPRKLT PLAYKQFSPN VAEKTLGASG
RYEGKVTPSS ERFKELTPNY NPDIIFKDEE NTGADRMMTQ RCKDKLNSLA ISVMNLWPGV
RLRVTEGWDE DGLHSEESLH YEGRAVDITT SDRDRNKYRM LARLAVEAGF DWVYYESKGH
VHCSVKSEHS VAAKTGGCFP GRALVTMKDG SHRQIRDLQA GDLVLASEGS DGTGDLIYSE
VLTFLDRRPI TQKHFYVIRT EDGASVSLTA AHLLFMRVGN CSNRGEPKPG AVRTIFASDA
QVGQCLLLGK LRKRFSQITH VGVREDQGLY PPLTAHGTVV VNDVLTSCYA AVNRQRLAHW
AFAPLRLLYS WTGPDQVLKN GLHWYSQVLI GLGKLLLDSE LFHPLALEAT ER
