DHH_HUMAN
ID DHH_HUMAN Reviewed; 396 AA.
AC O43323; Q15794;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-1998, sequence version 1.
DT 03-AUG-2022, entry version 193.
DE RecName: Full=Desert hedgehog protein {ECO:0000305};
DE Short=DHH;
DE EC=3.1.-.- {ECO:0000250|UniProtKB:Q62226};
DE AltName: Full=HHG-3;
DE Contains:
DE RecName: Full=Desert hedgehog protein N-product;
DE Short=DHH-N {ECO:0000303|PubMed:30298535};
DE Flags: Precursor;
GN Name=DHH {ECO:0000312|HGNC:HGNC:2865};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Tate G., Kishimoto K., Mitsuya T.;
RT "Expression of Sonic hedgehog and its receptor Patched/Smoothened in human
RT cancer cell lines and embryonic organs.";
RL J. Biochem. Mol. Biol. Biophys. 4:27-34(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 85-178.
RC TISSUE=Kidney;
RA Drummond I.A.;
RT "Human desert hedgehog.";
RL Submitted (JUL-1996) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP INVOLVEMENT IN GDMN.
RX PubMed=11017805; DOI=10.1086/321210;
RA Umehara F., Tate G., Itoh K., Yamaguchi N., Douchi T., Mitsuya T.,
RA Osame M.;
RT "A novel mutation of desert hedgehog in a patient with 46,XY partial
RT gonadal dysgenesis accompanied by minifascicular neuropathy.";
RL Am. J. Hum. Genet. 67:1302-1305(2000).
RN [5]
RP FUNCTION.
RX PubMed=11472839; DOI=10.1016/s0925-4773(01)00427-0;
RA Pathi S., Pagan-Westphal S., Baker D.P., Garber E.A., Rayhorn P.,
RA Bumcrot D., Tabin C.J., Blake Pepinsky R., Williams K.P.;
RT "Comparative biological responses to human Sonic, Indian, and Desert
RT hedgehog.";
RL Mech. Dev. 106:107-117(2001).
RN [6]
RP FUNCTION, DOMAIN, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=24342078; DOI=10.1016/j.mod.2013.12.002;
RA Pettigrew C.A., Asp E., Emerson C.P. Jr.;
RT "A new role for Hedgehogs in juxtacrine signaling.";
RL Mech. Dev. 131:137-149(2014).
RN [7]
RP PALMITOYLATION AT CYS-23, AND MUTAGENESIS OF CYS-23.
RX PubMed=24784881; DOI=10.1371/journal.pgen.1004340;
RA Callier P., Calvel P., Matevossian A., Makrythanasis P., Bernard P.,
RA Kurosaka H., Vannier A., Thauvin-Robinet C., Borel C., Mazaud-Guittot S.,
RA Rolland A., Desdoits-Lethimonier C., Guipponi M., Zimmermann C.,
RA Stevant I., Kuhne F., Conne B., Santoni F., Lambert S., Huet F.,
RA Mugneret F., Jaruzelska J., Faivre L., Wilhelm D., Jegou B., Trainor P.A.,
RA Resh M.D., Antonarakis S.E., Nef S.;
RT "Loss of function mutation in the palmitoyl-transferase HHAT leads to
RT syndromic 46,XY disorder of sex development by impeding Hedgehog protein
RT palmitoylation and signaling.";
RL PLoS Genet. 10:e1004340-e1004340(2014).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.85 ANGSTROMS) OF 39-194 IN COMPLEX WITH HHIP AND
RP ZINC IONS, CALCIUM-BINDING, DOMAIN, AND INTERACTION WITH HHIP.
RX PubMed=19561611; DOI=10.1038/nsmb.1607;
RA Bishop B., Aricescu A.R., Harlos K., O'Callaghan C.A., Jones E.Y.,
RA Siebold C.;
RT "Structural insights into hedgehog ligand sequestration by the human
RT hedgehog-interacting protein HHIP.";
RL Nat. Struct. Mol. Biol. 16:698-703(2009).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 24-189 IN COMPLEXES WITH BOC;
RP CDON; ZINC AND CALCIUM IONS, DOMAIN, AND INTERACTION WITH BOC AND CDON.
RX PubMed=20519495; DOI=10.1074/jbc.m110.131680;
RA Kavran J.M., Ward M.D., Oladosu O.O., Mulepati S., Leahy D.J.;
RT "All mammalian Hedgehog proteins interact with cell adhesion molecule,
RT down-regulated by oncogenes (CDO) and brother of CDO (BOC) in a conserved
RT manner.";
RL J. Biol. Chem. 285:24584-24590(2010).
RN [10]
RP VARIANT SRXY7 PRO-162.
RX PubMed=15356051; DOI=10.1210/jc.2004-0863;
RA Canto P., Soederlund D., Reyes E., Mendez J.P.;
RT "Mutations in the desert hedgehog (DHH) gene in patients with 46,XY
RT complete pure gonadal dysgenesis.";
RL J. Clin. Endocrinol. Metab. 89:4480-4483(2004).
RN [11]
RP ERRATUM OF PUBMED:15356051.
RA Canto P., Soederlund D., Reyes E., Mendez J.P.;
RL J. Clin. Endocrinol. Metab. 89:5453-5453(2004).
RN [12]
RP VARIANTS GDMN 176-TYR--GLY-396 DEL AND LYS-212, CHARACTERIZATION OF VARIANT
RP GDMN LYS-212, AND PTM.
RX PubMed=30298535; DOI=10.1002/humu.23664;
RA Tajouri A., Kharrat M., Hizem S., Zaghdoudi H., M'rad R.,
RA Simic-Schleicher G., Kaiser F.J., Hiort O., Werner R.;
RT "In vitro functional characterization of the novel DHH mutations
RT p.(Asn337Lysfs*24) and p.(Glu212Lys) associated with gonadal dysgenesis.";
RL Hum. Mutat. 39:2097-2109(2018).
RN [13]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=33063110; DOI=10.1093/cvr/cvaa285;
RA Hollier P.L., Chapouly C., Diop A., Guimbal S., Cornuault L., Gadeau A.P.,
RA Renault M.A.;
RT "Full-length Dhh and N-terminal Shh act as competitive antagonists to
RT regulate angiogenesis and vascular permeability.";
RL Cardiovasc. Res. 117:2489-2501(2021).
CC -!- FUNCTION: [Desert hedgehog protein]: The C-terminal part of the desert
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 (N-
CC product and C-product) followed by the covalent attachment of a
CC cholesterol moiety to the C-terminal of the newly generated N-product
CC (By similarity). Both activities occur in the reticulum endoplasmic (By
CC similarity). Functions in cell-cell mediated juxtacrine signaling
CC (PubMed:24342078). Promotes endothelium integrity (PubMed:33063110).
CC Binds to PTCH1 receptor, which functions in association with smoothened
CC (SMO), to activate the transcription of target genes in endothelial
CC cells (PubMed:33063110). In Schwann cells, controls the development of
CC the peripheral nerve sheath and the transition of mesenchymal cells to
CC form the epithelium-like structure of the perineurial tube (By
CC similarity). {ECO:0000250|UniProtKB:Q61488,
CC ECO:0000250|UniProtKB:Q62226, ECO:0000269|PubMed:24342078,
CC ECO:0000269|PubMed:33063110}.
CC -!- FUNCTION: [Desert hedgehog protein N-product]: The dually lipidated
CC desert hedgehog protein N-product is essential for a variety of
CC patterning events during development (By similarity). Binds to the
CC patched (PTCH1) receptor, which functions in association with
CC smoothened (SMO), to activate the transcription of target genes
CC (PubMed:11472839, PubMed:33063110). Required for normal testis
CC development and spermatogenesis, namely for the formation of adult-type
CC Leydig cells and normal development of peritubular cells and
CC seminiferous tubules (By similarity). Activates primary cilia signaling
CC on neighboring valve interstitial cells through a paracrine mechanism
CC (By similarity). May induce motor neurons in lateral neural tube and
CC may have a polarizing activity (PubMed:11472839). Prevents the desert
CC hedgehog protein precursor binding to PTCH1 (PubMed:33063110).
CC {ECO:0000250|UniProtKB:Q15465, ECO:0000250|UniProtKB:Q61488,
CC ECO:0000250|UniProtKB:Q62226, ECO:0000269|PubMed:11472839,
CC ECO:0000269|PubMed:33063110}.
CC -!- CATALYTIC ACTIVITY: [Desert 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: [Desert hedgehog protein N-product]: Multimer.
CC {ECO:0000250|UniProtKB:Q15465}.
CC -!- SUBUNIT: Interacts with BOC and CDON (PubMed:20519495). Interacts with
CC HHIP (PubMed:19561611). {ECO:0000269|PubMed:19561611,
CC ECO:0000269|PubMed:20519495}.
CC -!- INTERACTION:
CC O43323; Q9BWV1: BOC; NbExp=2; IntAct=EBI-11667804, EBI-718555;
CC O43323; Q4KMG0: CDON; NbExp=2; IntAct=EBI-11667804, EBI-7016840;
CC O43323; Q96QV1-1: HHIP; NbExp=4; IntAct=EBI-11667804, EBI-15791478;
CC -!- SUBCELLULAR LOCATION: [Desert hedgehog protein N-product]: Cell
CC membrane {ECO:0000250|UniProtKB:Q62226}; Lipid-anchor
CC {ECO:0000250|UniProtKB:Q62226}.
CC -!- SUBCELLULAR LOCATION: [Desert hedgehog protein]: Endoplasmic reticulum
CC membrane {ECO:0000250|UniProtKB:Q15465}. Golgi apparatus membrane
CC {ECO:0000250|UniProtKB:Q15465}. Secreted {ECO:0000269|PubMed:33063110}.
CC Cell membrane {ECO:0000269|PubMed:24342078}. Note=Co-localizes with
CC HHAT in the ER and Golgi membrane. {ECO:0000250|UniProtKB:Q15465}.
CC -!- DOMAIN: [Desert 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:0000269|PubMed:19561611, ECO:0000269|PubMed:20519495}.
CC -!- DOMAIN: [Desert hedgehog protein]: The C-terminal domain regulates the
CC auto-processing and controls the juxtacrine signaling.
CC {ECO:0000269|PubMed:24342078}.
CC -!- PTM: [Desert hedgehog protein]: Partially autoproteolyzed
CC (PubMed:30298535, PubMed:24342078). 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-terminal fragment (DhhN) (By
CC similarity). {ECO:0000250|UniProtKB:Q15465,
CC ECO:0000250|UniProtKB:Q62226, ECO:0000269|PubMed:24342078,
CC ECO:0000269|PubMed:30298535}.
CC -!- PTM: [Desert hedgehog protein 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 -!- DISEASE: 46,XY gonadal dysgenesis with minifascicular neuropathy (GDMN)
CC [MIM:607080]: An autosomal recessive disorder characterized by gonadal
CC dysgenesis associated with polyneuropathy. Genital anomalies include
CC the presence of a testis on one side and a streak or an absent gonad at
CC the other, persistence of Muellerian duct structures, and a variable
CC degree of genital ambiguity. {ECO:0000269|PubMed:11017805,
CC ECO:0000269|PubMed:30298535}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: 46,XY sex reversal 7 (SRXY7) [MIM:233420]: A disorder of sex
CC development. Affected individuals have a 46,XY karyotype but present as
CC phenotypically normal females. SRXY7 patients have no functional
CC gonads. {ECO:0000269|PubMed:15356051}. Note=The disease may be caused
CC by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the hedgehog family. {ECO:0000305}.
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DR EMBL; AB010994; BAA24866.1; -; Genomic_DNA.
DR EMBL; BC033507; AAH33507.1; -; mRNA.
DR EMBL; U59748; AAB03398.1; -; mRNA.
DR CCDS; CCDS8779.1; -.
DR PIR; G02735; G02735.
DR RefSeq; NP_066382.1; NM_021044.3.
DR PDB; 2WFQ; X-ray; 1.85 A; A=39-194.
DR PDB; 2WFR; X-ray; 1.95 A; A=39-194.
DR PDB; 2WG3; X-ray; 2.60 A; A/B=40-194.
DR PDB; 3N1G; X-ray; 1.90 A; A/B=24-189.
DR PDB; 3N1Q; X-ray; 2.89 A; A/B/E=24-189.
DR PDBsum; 2WFQ; -.
DR PDBsum; 2WFR; -.
DR PDBsum; 2WG3; -.
DR PDBsum; 3N1G; -.
DR PDBsum; 3N1Q; -.
DR AlphaFoldDB; O43323; -.
DR SMR; O43323; -.
DR BioGRID; 119151; 52.
DR DIP; DIP-48538N; -.
DR IntAct; O43323; 9.
DR STRING; 9606.ENSP00000266991; -.
DR MEROPS; C46.004; -.
DR iPTMnet; O43323; -.
DR PhosphoSitePlus; O43323; -.
DR BioMuta; DHH; -.
DR MassIVE; O43323; -.
DR PaxDb; O43323; -.
DR PeptideAtlas; O43323; -.
DR PRIDE; O43323; -.
DR ProteomicsDB; 48903; -.
DR Antibodypedia; 25833; 399 antibodies from 29 providers.
DR DNASU; 50846; -.
DR Ensembl; ENST00000649637.2; ENSP00000497483.1; ENSG00000139549.4.
DR GeneID; 50846; -.
DR KEGG; hsa:50846; -.
DR MANE-Select; ENST00000649637.2; ENSP00000497483.1; NM_021044.4; NP_066382.1.
DR UCSC; uc001rtf.4; human.
DR CTD; 50846; -.
DR DisGeNET; 50846; -.
DR GeneCards; DHH; -.
DR GeneReviews; DHH; -.
DR HGNC; HGNC:2865; DHH.
DR HPA; ENSG00000139549; Tissue enriched (testis).
DR MalaCards; DHH; -.
DR MIM; 233420; phenotype.
DR MIM; 605423; gene.
DR MIM; 607080; phenotype.
DR neXtProt; NX_O43323; -.
DR OpenTargets; ENSG00000139549; -.
DR Orphanet; 242; 46,XY complete gonadal dysgenesis.
DR Orphanet; 168563; 46,XY gonadal dysgenesis-motor and sensory neuropathy syndrome.
DR PharmGKB; PA27326; -.
DR VEuPathDB; HostDB:ENSG00000139549; -.
DR eggNOG; KOG3638; Eukaryota.
DR GeneTree; ENSGT00940000161132; -.
DR HOGENOM; CLU_034686_0_0_1; -.
DR InParanoid; O43323; -.
DR OMA; CGPGPRY; -.
DR OrthoDB; 1169356at2759; -.
DR PhylomeDB; O43323; -.
DR TreeFam; TF106458; -.
DR PathwayCommons; O43323; -.
DR Reactome; R-HSA-373080; Class B/2 (Secretin family receptors).
DR Reactome; R-HSA-5358346; Hedgehog ligand biogenesis.
DR Reactome; R-HSA-5362798; Release of Hh-Np from the secreting cell.
DR Reactome; R-HSA-5632681; Ligand-receptor interactions.
DR Reactome; R-HSA-5632684; Hedgehog 'on' state.
DR Reactome; R-HSA-5635838; Activation of SMO.
DR Reactome; R-HSA-5658034; HHAT G278V doesn't palmitoylate Hh-Np.
DR Reactome; R-HSA-9690406; Transcriptional regulation of testis differentiation.
DR SignaLink; O43323; -.
DR BioGRID-ORCS; 50846; 14 hits in 1079 CRISPR screens.
DR EvolutionaryTrace; O43323; -.
DR GeneWiki; Desert_hedgehog_protein; -.
DR GenomeRNAi; 50846; -.
DR Pharos; O43323; Tbio.
DR PRO; PR:O43323; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; O43323; protein.
DR Bgee; ENSG00000139549; Expressed in tibial nerve and 78 other tissues.
DR Genevisible; O43323; HS.
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; IDA:UniProtKB.
DR GO; GO:0005113; F:patched binding; IDA:UniProtKB.
DR GO; GO:0008233; F:peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0001708; P:cell fate specification; IBA:GO_Central.
DR GO; GO:0007267; P:cell-cell signaling; 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:0042552; P:myelination; IEA:Ensembl.
DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IDA:UniProtKB.
DR GO; GO:0016540; P:protein autoprocessing; IEA:InterPro.
DR GO; GO:0010468; P:regulation of gene expression; IBA:GO_Central.
DR GO; GO:0050810; P:regulation of steroid biosynthetic process; IEA:Ensembl.
DR GO; GO:0032355; P:response to estradiol; IEA:Ensembl.
DR GO; GO:0043627; P:response to estrogen; IEA:Ensembl.
DR GO; GO:0007224; P:smoothened signaling pathway; IBA:GO_Central.
DR GO; GO:0007286; P:spermatid development; IEA:Ensembl.
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 1: Evidence at protein level;
KW 3D-structure; Autocatalytic cleavage; Calcium; Cell membrane;
KW Developmental protein; Disease variant; Endoplasmic reticulum;
KW Golgi apparatus; Hydrolase; Lipoprotein; Membrane; Metal-binding;
KW Palmitate; Protease; Reference proteome; Secreted; Signal; Zinc.
FT SIGNAL 1..22
FT /evidence="ECO:0000255"
FT CHAIN 23..396
FT /note="Desert hedgehog protein"
FT /id="PRO_0000013244"
FT CHAIN 23..198
FT /note="Desert hedgehog protein N-product"
FT /id="PRO_0000013245"
FT BINDING 90
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:19561611,
FT ECO:0000269|PubMed:20519495, ECO:0007744|PDB:2WFR,
FT ECO:0007744|PDB:3N1G, ECO:0007744|PDB:3N1Q"
FT BINDING 91
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:19561611,
FT ECO:0000269|PubMed:20519495, ECO:0007744|PDB:2WFR,
FT ECO:0007744|PDB:3N1G, ECO:0007744|PDB:3N1Q"
FT BINDING 91
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:19561611,
FT ECO:0000269|PubMed:20519495, ECO:0007744|PDB:2WFR,
FT ECO:0007744|PDB:3N1G, ECO:0007744|PDB:3N1Q"
FT BINDING 96
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:19561611,
FT ECO:0000269|PubMed:20519495, ECO:0007744|PDB:2WFR,
FT ECO:0007744|PDB:3N1G, ECO:0007744|PDB:3N1Q"
FT BINDING 126
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:19561611,
FT ECO:0000269|PubMed:20519495, ECO:0007744|PDB:2WFR,
FT ECO:0007744|PDB:3N1G, ECO:0007744|PDB:3N1Q"
FT BINDING 127
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000269|PubMed:19561611,
FT ECO:0000269|PubMed:20519495, ECO:0007744|PDB:2WFR,
FT ECO:0007744|PDB:3N1G, ECO:0007744|PDB:3N1Q"
FT BINDING 127
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:19561611,
FT ECO:0000269|PubMed:20519495, ECO:0007744|PDB:2WFR,
FT ECO:0007744|PDB:3N1G, ECO:0007744|PDB:3N1Q"
FT BINDING 130
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:19561611,
FT ECO:0000269|PubMed:20519495, ECO:0007744|PDB:2WFR,
FT ECO:0007744|PDB:3N1G, ECO:0007744|PDB:3N1Q"
FT BINDING 132
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000269|PubMed:19561611,
FT ECO:0000269|PubMed:20519495, ECO:0007744|PDB:2WFR,
FT ECO:0007744|PDB:3N1G, ECO:0007744|PDB:3N1Q"
FT BINDING 141
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:19561611,
FT ECO:0000269|PubMed:20519495, ECO:0007744|PDB:2WFQ,
FT ECO:0007744|PDB:2WFR, ECO:0007744|PDB:2WG3,
FT ECO:0007744|PDB:3N1G, ECO:0007744|PDB:3N1Q"
FT BINDING 148
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:19561611,
FT ECO:0000269|PubMed:20519495, ECO:0007744|PDB:2WFQ,
FT ECO:0007744|PDB:2WFR, ECO:0007744|PDB:2WG3,
FT ECO:0007744|PDB:3N1G, ECO:0007744|PDB:3N1Q"
FT BINDING 183
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000269|PubMed:19561611,
FT ECO:0000269|PubMed:20519495, ECO:0007744|PDB:2WFQ,
FT ECO:0007744|PDB:2WFR, ECO:0007744|PDB:2WG3,
FT ECO:0007744|PDB:3N1G, ECO:0007744|PDB:3N1Q"
FT SITE 198..199
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:Q02936"
FT SITE 244
FT /note="Involved in cholesterol transfer"
FT /evidence="ECO:0000250|UniProtKB:Q02936"
FT SITE 268
FT /note="Involved in auto-cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q02936"
FT SITE 271
FT /note="Essential for auto-cleavage"
FT /evidence="ECO:0000250|UniProtKB:Q02936"
FT LIPID 23
FT /note="N-palmitoyl cysteine"
FT /evidence="ECO:0000269|PubMed:24784881"
FT LIPID 198
FT /note="Cholesterol glycine ester"
FT /evidence="ECO:0000250|UniProtKB:Q62226"
FT VARIANT 162
FT /note="L -> P (in SRXY7; dbSNP:rs111033589)"
FT /evidence="ECO:0000269|PubMed:15356051"
FT /id="VAR_054873"
FT VARIANT 176..396
FT /note="Missing (in GDMN; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:30298535"
FT /id="VAR_086512"
FT VARIANT 212
FT /note="E -> K (in GDMN; unknown pathological significance;
FT Reduces cleavage efficiency in in vitro time course)"
FT /evidence="ECO:0000269|PubMed:30298535"
FT /id="VAR_086513"
FT MUTAGEN 23
FT /note="C->A: Loss of palmitoylation."
FT /evidence="ECO:0000269|PubMed:24784881"
FT CONFLICT 177
FT /note="E -> G (in Ref. 3; AAB03398)"
FT /evidence="ECO:0000305"
FT STRAND 48..52
FT /evidence="ECO:0007829|PDB:2WFQ"
FT TURN 57..60
FT /evidence="ECO:0007829|PDB:2WFQ"
FT HELIX 73..76
FT /evidence="ECO:0007829|PDB:2WFQ"
FT STRAND 85..87
FT /evidence="ECO:0007829|PDB:2WFQ"
FT STRAND 92..94
FT /evidence="ECO:0007829|PDB:2WFQ"
FT HELIX 95..97
FT /evidence="ECO:0007829|PDB:2WFQ"
FT HELIX 101..117
FT /evidence="ECO:0007829|PDB:2WFQ"
FT STRAND 123..127
FT /evidence="ECO:0007829|PDB:2WFQ"
FT HELIX 140..143
FT /evidence="ECO:0007829|PDB:2WFQ"
FT STRAND 146..151
FT /evidence="ECO:0007829|PDB:2WFQ"
FT HELIX 156..158
FT /evidence="ECO:0007829|PDB:2WFQ"
FT HELIX 159..168
FT /evidence="ECO:0007829|PDB:2WFQ"
FT STRAND 172..178
FT /evidence="ECO:0007829|PDB:2WFQ"
FT STRAND 181..185
FT /evidence="ECO:0007829|PDB:2WFQ"
FT HELIX 192..195
FT /evidence="ECO:0007829|PDB:2WFQ"
SQ SEQUENCE 396 AA; 43577 MW; FCE4FB21972C3AD5 CRC64;
MALLTNLLPL CCLALLALPA QSCGPGRGPV GRRRYARKQL VPLLYKQFVP GVPERTLGAS
GPAEGRVARG SERFRDLVPN YNPDIIFKDE ENSGADRLMT ERCKERVNAL AIAVMNMWPG
VRLRVTEGWD EDGHHAQDSL HYEGRALDIT TSDRDRNKYG LLARLAVEAG FDWVYYESRN
HVHVSVKADN SLAVRAGGCF PGNATVRLWS GERKGLRELH RGDWVLAADA SGRVVPTPVL
LFLDRDLQRR ASFVAVETEW PPRKLLLTPW HLVFAARGPA PAPGDFAPVF ARRLRAGDSV
LAPGGDALRP ARVARVAREE AVGVFAPLTA HGTLLVNDVL ASCYAVLESH QWAHRAFAPL
RLLHALGALL PGGAVQPTGM HWYSRLLYRL AEELLG
