DHHB_XENLA
ID DHHB_XENLA Reviewed; 398 AA.
AC Q91611;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 113.
DE RecName: Full=Desert hedgehog protein B {ECO:0000305};
DE EC=3.1.-.- {ECO:0000250|UniProtKB:Q62226};
DE AltName: Full=Desert hedgehog protein 2;
DE Short=DHH-2;
DE AltName: Full=Hedgehog protein 4;
DE AltName: Full=X-HH4;
DE Contains:
DE RecName: Full=Desert hedgehog protein B N-product;
DE Flags: Precursor;
GN Name=dhh-b; Synonyms=hh4;
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], AND FUNCTION.
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: [Desert hedgehog protein B]: The C-terminal part of the
CC desert 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 (DhhN
CC and DhhC) followed by the covalent attachment of a cholesterol moiety
CC to the C-terminal of the newly generated DhhN (By similarity). Both
CC activities occur in the reticulum endoplasmic (By similarity).
CC {ECO:0000250|UniProtKB:Q62226}.
CC -!- FUNCTION: [Desert hedgehog protein B N-product]: The dually lipidated
CC desert hedgehog protein N-product (DhhNp) is essential for a variety of
CC patterning events during development (By similarity). Involved in the
CC early induction and patterning of anterodorsal ectoderm, nervous system
CC and somites. Induces ectopic cement gland formation in embryos
CC (PubMed:7671800). Binds to the patched (PTCH1) receptor, which
CC functions in association with smoothened (SMO), to activate the
CC transcription of target genes (By similarity).
CC {ECO:0000250|UniProtKB:O43323, ECO:0000250|UniProtKB:Q62226,
CC ECO:0000269|PubMed:7671800}.
CC -!- CATALYTIC ACTIVITY: [Desert hedgehog protein B]:
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: [Desert hedgehog protein B N-product]: Multimer.
CC {ECO:0000250|UniProtKB:Q15465}.
CC -!- SUBUNIT: Interacts with BOC and CDON. Interacts with HHIP.
CC {ECO:0000250|UniProtKB:O43323}.
CC -!- SUBCELLULAR LOCATION: [Desert hedgehog protein B N-product]: Cell
CC membrane {ECO:0000250|UniProtKB:Q62226}; Lipid-anchor
CC {ECO:0000250|UniProtKB:Q62226}.
CC -!- SUBCELLULAR LOCATION: [Desert hedgehog protein B]: Endoplasmic
CC reticulum membrane {ECO:0000250|UniProtKB:Q15465}. Golgi apparatus
CC membrane {ECO:0000250|UniProtKB:Q15465}. Secreted
CC {ECO:0000250|UniProtKB:O43323}. Cell membrane
CC {ECO:0000250|UniProtKB:O43323}. Note=Co-localizes with HHAT in the ER
CC and Golgi membrane. {ECO:0000250|UniProtKB:Q15465}.
CC -!- DOMAIN: [Desert hedgehog protein B 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:O43323}.
CC -!- DOMAIN: [Desert hedgehog protein B]: The C-terminal domain regulates
CC the auto-processing and controls the juxtacrine signaling.
CC {ECO:0000250|UniProtKB:O43323}.
CC -!- PTM: [Desert hedgehog protein B]: Partially autoproteolyzed (By
CC similarity). The C-terminal domain displays an autoproteolysis activity
CC and a cholesterol transferase activity (By similarity). Both activities
CC result in the cleavage of the full-length protein and covalent
CC attachment of a cholesterol moiety to the C-terminal of the newly
CC generated N-terminal fragment (DhhN) (By similarity).
CC {ECO:0000250|UniProtKB:O43323, ECO:0000250|UniProtKB:Q62226}.
CC -!- PTM: [Desert hedgehog protein B N-product]: N-palmitoylation by HHAT of
CC DhhN is required for desert hedgehog protein N-product multimerization
CC and full activity (By similarity). {ECO:0000250|UniProtKB:Q62226}.
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; U26350; AAA85164.1; -; mRNA.
DR RefSeq; NP_001079261.1; NM_001085792.1.
DR AlphaFoldDB; Q91611; -.
DR SMR; Q91611; -.
DR MEROPS; C46.004; -.
DR GeneID; 378539; -.
DR KEGG; xla:378539; -.
DR CTD; 378539; -.
DR Xenbase; XB-GENE-6252656; dhh.S.
DR OMA; CANSEIC; -.
DR OrthoDB; 1169356at2759; -.
DR Proteomes; UP000186698; Chromosome 2S.
DR Bgee; 378539; Expressed in camera-type eye and 8 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 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..398
FT /note="Desert hedgehog protein B"
FT /id="PRO_0000013253"
FT CHAIN 24..199
FT /note="Desert hedgehog protein B N-product"
FT /id="PRO_0000013254"
FT BINDING 91
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O43323"
FT BINDING 92
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O43323"
FT BINDING 92
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O43323"
FT BINDING 97
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O43323"
FT BINDING 127
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O43323"
FT BINDING 128
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O43323"
FT BINDING 128
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O43323"
FT BINDING 131
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O43323"
FT BINDING 133
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O43323"
FT BINDING 142
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O43323"
FT BINDING 149
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O43323"
FT BINDING 184
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O43323"
FT SITE 199..200
FT /note="Cleavage; by autolysis"
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:O43323"
FT LIPID 199
FT /note="Cholesterol glycine ester"
FT /evidence="ECO:0000250|UniProtKB:Q62226"
SQ SEQUENCE 398 AA; 44458 MW; DBC23AF85F69DD08 CRC64;
MPAVRILILA ACCCWLLLLP VRCCGPGRGP VGGRRRYMRR LVPLLYKQFV PNVPEKTLGA
SGKSEGKIRR GSERFIKLVP NYNPDIIFKD EENTGADRLM TERCKDRVNA LAISVMNMWP
GLKLRVTEGW DEDGHHAHDS LHYEGRALDI TTSDRDRNKY GMLARLAVEA GFDWVYYESK
AHIHVSVNTD NSLGVRSGGC FPGTAMVMME TGKKKPLSEL KLGDTVFTTD ETGLLIHSVV
LLFLHRDPYK TATFVLIEAE GHPTKLLVTP NHLLFIKSSS STGFQPTFAY RVQIGDLIQI
YVNGTQVQSS KVVRVSVDEQ TGVYAPMTEH GTLLVDGVLT SCYATVESHT LAHASLAPLR
LFQGIASMLP DLHTSDGVHW YCHILYVLAK YVLWWDMP
