DHHA_XENLA
ID DHHA_XENLA Reviewed; 396 AA.
AC Q91610;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 118.
DE RecName: Full=Desert hedgehog protein A {ECO:0000305};
DE EC=3.1.-.- {ECO:0000250|UniProtKB:Q62226};
DE AltName: Full=Cephalic hedgehog protein;
DE AltName: Full=Desert hedgehog protein 1;
DE Short=DHH-1;
DE AltName: Full=X-CHH;
DE Contains:
DE RecName: Full=Desert hedgehog protein A N-product;
DE Flags: Precursor;
GN Name=dhh-a; Synonyms=chh;
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], FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
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 A]: 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 A 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 A]:
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 A 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 A N-product]: Cell
CC membrane {ECO:0000250|UniProtKB:Q62226}; Lipid-anchor
CC {ECO:0000250|UniProtKB:Q62226}.
CC -!- SUBCELLULAR LOCATION: [Desert hedgehog protein A]: 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 -!- TISSUE SPECIFICITY: Expressed in the marginal zone at early
CC gastrulation. In the neurula, expression is restricted to anterior
CC structures, encompassing both neural plate and endodermal cells.
CC Expressed on the inner surface of the pharynx at the early tadpole
CC stage. {ECO:0000269|PubMed:7671800}.
CC -!- DEVELOPMENTAL STAGE: First expressed during early gastrulation.
CC Expression peaks during neural induction and early organogenesis.
CC {ECO:0000269|PubMed:7671800}.
CC -!- DOMAIN: [Desert hedgehog protein A 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 A]: The C-terminal domain regulates
CC the auto-processing and controls the juxtacrine signaling.
CC {ECO:0000250|UniProtKB:O43323}.
CC -!- PTM: [Desert hedgehog protein A]: 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 A 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}.
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DR EMBL; U26349; AAA85163.1; -; mRNA.
DR RefSeq; NP_001079260.1; NM_001085791.1.
DR AlphaFoldDB; Q91610; -.
DR SMR; Q91610; -.
DR MEROPS; C46.004; -.
DR GeneID; 378538; -.
DR KEGG; xla:378538; -.
DR CTD; 378538; -.
DR Xenbase; XB-GENE-864981; dhh.L.
DR OMA; CGPGPRY; -.
DR OrthoDB; 1169356at2759; -.
DR Proteomes; UP000186698; Chromosome 2L.
DR Bgee; 378538; Expressed in camera-type eye and 13 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:0016539; P:intein-mediated protein splicing; IEA:InterPro.
DR GO; GO:0016540; P:protein autoprocessing; IEA:InterPro.
DR GO; GO:0048731; P:system development; IEA:UniProt.
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; IPR006141; Intein_N.
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..22
FT /evidence="ECO:0000255"
FT CHAIN 23..396
FT /note="Desert hedgehog protein A"
FT /id="PRO_0000013250"
FT CHAIN 23..197
FT /note="Desert hedgehog protein A N-product"
FT /id="PRO_0000013251"
FT BINDING 89
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O43323"
FT BINDING 90
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O43323"
FT BINDING 90
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O43323"
FT BINDING 95
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O43323"
FT BINDING 125
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O43323"
FT BINDING 126
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:O43323"
FT BINDING 126
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:O43323"
FT BINDING 129
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 140
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O43323"
FT BINDING 147
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O43323"
FT BINDING 182
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:O43323"
FT SITE 197..198
FT /note="Cleavage; by autolysis"
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 23
FT /note="N-palmitoyl cysteine"
FT /evidence="ECO:0000250|UniProtKB:O43323"
FT LIPID 197
FT /note="Cholesterol glycine ester"
FT /evidence="ECO:0000250|UniProtKB:Q62226"
SQ SEQUENCE 396 AA; 44087 MW; 774A3EC2268A5EE9 CRC64;
MPAVRIVILA ICCGLLLVPV RCCGPGRGPV GRRRYMRKLV PLHYKQFVPN VPEKTLGASG
KSEGKIHRGS ERFIELVPNY NPDIIFKDEE KTGADRLMTE RCKDRVNALA ISVMNMWPGV
KLRVTEGWDE DGHHAHDSLH YEGRALDITT SDRDRNKYGM LARLAVEAGF DWVYYESKAH
IHVSVKADNS LGVRSGGCFP GTAMVMMGTG ERKPLSELKI GDTVYTTDET GQLITSVVLL
FLHRNPYKTA TFVLIEAEGH PSKLLVTPNH LLFIQSSSSA GFLPTFAYRV QIGDLVQIYV
NGTQVQSSKV VRVSLEEQTG VYAPMTEHGT LLVDGVLTSC YATVESHTLA HVSLAPLRLF
QGIASMLPDL DMSDGVHWYC HILYVLAKYV LWWDMP
