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 24-JAN-2024, entry version 201. 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=10.1016/s0002-9297(07)62958-9; 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}. 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; 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.ENSP00000497483; -. DR MEROPS; C46.004; -. DR iPTMnet; O43323; -. DR PhosphoSitePlus; O43323; -. DR BioMuta; DHH; -. DR MassIVE; O43323; -. DR PaxDb; 9606-ENSP00000266991; -. DR PeptideAtlas; O43323; -. DR ProteomicsDB; 48903; -. DR Antibodypedia; 25833; 415 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 AGR; HGNC:2865; -. 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; WWARLAQ; -. DR OrthoDB; 197397at2759; -. 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 1155 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 79 other cell types or tissues. DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. 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; IDA:UniProtKB. DR GO; GO:0140853; F:cholesterol-protein transferase activity; ISS:UniProtKB. DR GO; GO:0005113; F:patched binding; IDA:UniProtKB. DR GO; GO:0008233; F:peptidase activity; ISS:UniProtKB. 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:0097264; P:self proteolysis; ISS:UniProtKB. DR GO; GO:0007224; P:smoothened signaling pathway; IBA:GO_Central. 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 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 Genevisible; O43323; HS. 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; Transferase; KW 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; uncertain significance)" FT /evidence="ECO:0000269|PubMed:30298535" FT /id="VAR_086512" FT VARIANT 212 FT /note="E -> K (in GDMN; uncertain significance; Reduces FT cleavage efficiency in in vitro time course; FT dbSNP:rs1480612338)" 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 //