ID A0A3Q7SKR1_VULVU Unreviewed; 396 AA.
AC A0A3Q7SKR1;
DT 10-APR-2019, integrated into UniProtKB/TrEMBL.
DT 10-APR-2019, sequence version 1.
DT 27-MAR-2024, entry version 27.
DE RecName: Full=Hedgehog protein {ECO:0000256|RuleBase:RU280812};
GN Name=DHH {ECO:0000313|RefSeq:XP_025856026.1};
OS Vulpes vulpes (Red fox).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Vulpes.
OX NCBI_TaxID=9627 {ECO:0000313|Proteomes:UP000286640, ECO:0000313|RefSeq:XP_025856026.1};
RN [1]
RP IDENTIFICATION.
RG RefSeq;
RL Submitted (JAN-2019) to UniProtKB.
RN [2] {ECO:0000313|RefSeq:XP_025856026.1}
RP IDENTIFICATION.
RC STRAIN=TameXAggressive cross {ECO:0000313|RefSeq:XP_025856026.1};
RC TISSUE=Blood {ECO:0000313|RefSeq:XP_025856026.1};
RG RefSeq;
RL Submitted (NOV-2023) to UniProtKB.
CC -!- FUNCTION: [Protein hedgehog N-product]: The dually lipidated hedgehog
CC protein N-product is a morphogen which is essential for a variety of
CC patterning events during development. {ECO:0000256|RuleBase:RU280812}.
CC -!- FUNCTION: [Protein hedgehog]: The C-terminal part of the hedgehog
CC protein precursor displays an autoproteolysis activity that results in
CC the cleavage of the full-length protein into two parts (N-product and
CC C-product). In addition, the C-terminal part displays a cholesterol
CC transferase activity that results by the covalent attachment of a
CC cholesterol moiety to the C-terminal of the newly generated N-product.
CC {ECO:0000256|RuleBase:RU280812}.
CC -!- CATALYTIC ACTIVITY:
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:0000256|ARBA:ARBA00034065};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59505;
CC Evidence={ECO:0000256|ARBA:ARBA00034065};
CC -!- SUBUNIT: Multimer. {ECO:0000256|ARBA:ARBA00034131}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000256|ARBA:ARBA00004586}. Membrane
CC {ECO:0000256|ARBA:ARBA00004635}; Lipid-anchor
CC {ECO:0000256|ARBA:ARBA00004635}.
CC -!- SUBCELLULAR LOCATION: [Sonic hedgehog protein]: Endoplasmic reticulum
CC membrane {ECO:0000256|RuleBase:RU280812}. Golgi apparatus membrane
CC {ECO:0000256|RuleBase:RU280812}.
CC -!- SUBCELLULAR LOCATION: [Protein hedgehog N-product]: Cell membrane
CC {ECO:0000256|RuleBase:RU280812}; Lipid-anchor
CC {ECO:0000256|RuleBase:RU280812}.
CC -!- SIMILARITY: Belongs to the hedgehog family.
CC {ECO:0000256|ARBA:ARBA00010649, ECO:0000256|RuleBase:RU280812}.
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DR RefSeq; XP_025856026.1; XM_026000241.1.
DR AlphaFoldDB; A0A3Q7SKR1; -.
DR STRING; 9627.ENSVVUP00000028550; -.
DR Ensembl; ENSVVUT00000037944; ENSVVUP00000028550; ENSVVUG00000020895.
DR KEGG; vvp:112921102; -.
DR OMA; WWARLAQ; -.
DR OrthoDB; 197397at2759; -.
DR Proteomes; UP000286640; Unplaced.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005509; F:calcium ion binding; IEA:Ensembl.
DR GO; GO:0005113; F:patched binding; IEA:Ensembl.
DR GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:Ensembl.
DR GO; GO:0007267; P:cell-cell signaling; IEA:InterPro.
DR GO; GO:0016539; P:intein-mediated protein splicing; IEA:InterPro.
DR GO; GO:0033327; P:Leydig cell differentiation; IEA:Ensembl.
DR GO; GO:0030238; P:male sex determination; IEA:Ensembl.
DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IEA:Ensembl.
DR GO; GO:0016540; P:protein autoprocessing; IEA:InterPro.
DR GO; GO:0050810; P:regulation of steroid biosynthetic process; IEA:Ensembl.
DR GO; GO:0007224; P:smoothened signaling pathway; IEA:Ensembl.
DR GO; GO:0007286; P:spermatid development; IEA:Ensembl.
DR CDD; cd00081; Hint; 1.
DR Gene3D; 3.30.1380.10; -; 1.
DR Gene3D; 2.170.16.10; Hedgehog/Intein (Hint) domain; 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 PANTHER; PTHR11889:SF56; DESERT HEDGEHOG PROTEIN; 1.
DR PANTHER; PTHR11889; HEDGEHOG; 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; SSF55166; Hedgehog/DD-peptidase; 1.
DR SUPFAM; SSF51294; Hedgehog/intein (Hint) domain; 1.
DR PROSITE; PS50817; INTEIN_N_TER; 1.
PE 3: Inferred from homology;
KW Autocatalytic cleavage {ECO:0000256|ARBA:ARBA00022813,
KW ECO:0000256|RuleBase:RU280812};
KW Calcium {ECO:0000256|ARBA:ARBA00022837, ECO:0000256|PIRSR:PIRSR009400-2};
KW Cell membrane {ECO:0000256|ARBA:ARBA00022475,
KW ECO:0000256|RuleBase:RU280812};
KW Developmental protein {ECO:0000256|ARBA:ARBA00022473,
KW ECO:0000256|RuleBase:RU280812};
KW Endoplasmic reticulum {ECO:0000256|RuleBase:RU280812};
KW Golgi apparatus {ECO:0000256|RuleBase:RU280812};
KW Hydrolase {ECO:0000256|ARBA:ARBA00022801, ECO:0000256|RuleBase:RU280812};
KW Lipoprotein {ECO:0000256|ARBA:ARBA00023288};
KW Membrane {ECO:0000256|ARBA:ARBA00023136, ECO:0000256|RuleBase:RU280812};
KW Metal-binding {ECO:0000256|ARBA:ARBA00022723,
KW ECO:0000256|PIRSR:PIRSR009400-2};
KW Palmitate {ECO:0000256|ARBA:ARBA00023139};
KW Protease {ECO:0000256|ARBA:ARBA00022670, ECO:0000256|RuleBase:RU280812};
KW Reference proteome {ECO:0000313|Proteomes:UP000286640};
KW Signal {ECO:0000256|ARBA:ARBA00022729, ECO:0000256|RuleBase:RU280812};
KW Transferase {ECO:0000256|ARBA:ARBA00022679};
KW Zinc {ECO:0000256|ARBA:ARBA00022833, ECO:0000256|PIRSR:PIRSR009400-2}.
FT SIGNAL 1..22
FT /evidence="ECO:0000256|SAM:SignalP"
FT CHAIN 23..396
FT /note="Hedgehog protein"
FT /evidence="ECO:0000256|SAM:SignalP"
FT /id="PRO_5018635930"
FT DOMAIN 197..304
FT /note="Hint"
FT /evidence="ECO:0000259|SMART:SM00306"
FT DOMAIN 305..349
FT /note="Hint"
FT /evidence="ECO:0000259|SMART:SM00305"
FT BINDING 90
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000256|PIRSR:PIRSR009400-2"
FT BINDING 91
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000256|PIRSR:PIRSR009400-2"
FT BINDING 91
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000256|PIRSR:PIRSR009400-2"
FT BINDING 96
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000256|PIRSR:PIRSR009400-2"
FT BINDING 126
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000256|PIRSR:PIRSR009400-2"
FT BINDING 127
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000256|PIRSR:PIRSR009400-2"
FT BINDING 127
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000256|PIRSR:PIRSR009400-2"
FT BINDING 130
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000256|PIRSR:PIRSR009400-2"
FT BINDING 132
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000256|PIRSR:PIRSR009400-2"
FT BINDING 141
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000256|PIRSR:PIRSR009400-2"
FT BINDING 148
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000256|PIRSR:PIRSR009400-2"
FT BINDING 183
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000256|PIRSR:PIRSR009400-2"
FT SITE 198..199
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000256|PIRSR:PIRSR009400-1"
FT SITE 244
FT /note="Involved in cholesterol transfer"
FT /evidence="ECO:0000256|PIRSR:PIRSR009400-1"
FT SITE 268
FT /note="Involved in auto-cleavage"
FT /evidence="ECO:0000256|PIRSR:PIRSR009400-1"
FT SITE 271
FT /note="Essential for auto-cleavage"
FT /evidence="ECO:0000256|PIRSR:PIRSR009400-1"
SQ SEQUENCE 396 AA; 43575 MW; 5081BB895C10FB4A CRC64;
MALPARLVPL CCLALLALPA QSCGPGRGPV GRRRYVRKQL VPLLYKQFVP SVPERTLGAS
GPAEGRVARG SERFRDLVPN YNPDIIFKDE ENSGADRLMT ERCKERVNAL AIAVMNMWPG
VRLRVTEGWD EDGHHAQDSL HYEGRALDIT TSDRDRNKYG LLARLAVEAG FDWVYYESRN
HVHVSVKADN SLAVRAGGCF PGNATVRLRS GERKGLRELH RGDWVLAADA AGRVVPTPVL
LFLDRDLQRR ASFVAVETER PPRKLLLTPW HLVFAARGPA PAPGDFAPVF ARRLRAGDSV
LAPGGDALRP ARVARVAREE AVGVFAPLTA HGTLLVNDVL ASCYAVLESH QWAHRAFAPL
RLLHALGALL PGGAVQPTGM HWYSRFLYRL AEELLG
//
