SC5D_HUMAN
ID SC5D_HUMAN Reviewed; 299 AA.
AC O75845; O00119; Q6GTM5; Q9UK15;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Lathosterol oxidase {ECO:0000305};
DE EC=1.14.19.20 {ECO:0000269|PubMed:10786622};
DE AltName: Full=C-5 sterol desaturase;
DE AltName: Full=Delta(7)-sterol 5-desaturase;
DE AltName: Full=Delta(7)-sterol C5(6)-desaturase;
DE AltName: Full=Lathosterol 5-desaturase;
DE AltName: Full=Sterol-C5-desaturase;
GN Name=SC5D {ECO:0000312|HGNC:HGNC:10547}; Synonyms=SC5DL;
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 [MRNA].
RX PubMed=8976377; DOI=10.1159/000134427;
RA Matsushima M., Inazawa J., Takahashi E., Suzumori K., Nakamura Y.;
RT "Molecular cloning and mapping of a human cDNA(SC5DL) encoding a protein
RT homologous to fungal sterol-C5-desaturase.";
RL Cytogenet. Cell Genet. 74:252-254(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=B-cell;
RX PubMed=10344195; DOI=10.1023/a:1006113919172;
RA Husselstein T., Schaller H., Gachotte D., Benveniste P.;
RT "Delta7-sterol-C5-desaturase: molecular characterization and functional
RT expression of wild-type and mutant alleles.";
RL Plant Mol. Biol. 39:891-906(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND CATALYTIC ACTIVITY.
RC TISSUE=Liver;
RX PubMed=10786622; DOI=10.1016/s0167-4781(99)00248-1;
RA Nishi S., Nishino H., Ishibashi T.;
RT "cDNA cloning of the mammalian sterol C5-desaturase and the expression in
RT yeast mutant.";
RL Biochim. Biophys. Acta 1490:106-108(2000).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Sugawara T.;
RT "Human sterol C5 desaturase promoter.";
RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain, and Kidney;
RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y.,
RA Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung;
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 [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-253, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [10]
RP VARIANTS LATHOS GLN-29 AND ASP-211.
RX PubMed=12189593; DOI=10.1086/342668;
RA Brunetti-Pierri N., Corso G., Rossi M., Ferrari P., Balli F., Rivasi F.,
RA Annunziata I., Ballabio A., Dello Russo A., Andria G., Parenti G.;
RT "Lathosterolosis, a novel multiple-malformation/mental retardation syndrome
RT due to deficiency of 3beta-hydroxysteroid-delta5-desaturase.";
RL Am. J. Hum. Genet. 71:952-958(2002).
RN [11]
RP VARIANT LATHOS SER-46.
RX PubMed=12812989; DOI=10.1093/hmg/ddg172;
RA Krakowiak P.A., Wassif C.A., Kratz L., Cozma D., Kovarova M., Harris G.,
RA Grinberg A., Yang Y., Hunter A.G.W., Tsokos M., Kelley R.I., Porter F.D.;
RT "Lathosterolosis: an inborn error of human and murine cholesterol synthesis
RT due to lathosterol 5-desaturase deficiency.";
RL Hum. Mol. Genet. 12:1631-1641(2003).
CC -!- FUNCTION: Catalyzes a dehydrogenation to introduce C5-6 double bond
CC into lathosterol in cholesterol biosynthesis.
CC {ECO:0000269|PubMed:10786622}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a Delta(7)-sterol + 2 Fe(II)-[cytochrome b5] + 2 H(+) + O2 = a
CC Delta(5),Delta(7)-sterol + 2 Fe(III)-[cytochrome b5] + 2 H2O;
CC Xref=Rhea:RHEA:54320, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:29033, ChEBI:CHEBI:29034, ChEBI:CHEBI:138130,
CC ChEBI:CHEBI:138131; EC=1.14.19.20;
CC Evidence={ECO:0000305|PubMed:10786622};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54321;
CC Evidence={ECO:0000305|PubMed:10786622};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 Fe(II)-[cytochrome b5] + 2 H(+) + lathosterol + O2 = 7-
CC dehydrocholesterol + 2 Fe(III)-[cytochrome b5] + 2 H2O;
CC Xref=Rhea:RHEA:46556, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17168, ChEBI:CHEBI:17759, ChEBI:CHEBI:29033,
CC ChEBI:CHEBI:29034; EC=1.14.19.20;
CC Evidence={ECO:0000269|PubMed:10786622};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46557;
CC Evidence={ECO:0000305|PubMed:10786622};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875; Evidence={ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000305}.
CC -!- DOMAIN: The histidine box domains may contain the active site and/or be
CC involved in metal ion binding.
CC -!- DISEASE: Lathosterolosis (LATHOS) [MIM:607330]: An autosomal recessive
CC disorder characterized by multiple congenital anomalies affecting axial
CC and appendicular skeleton, liver, central nervous and urogenital
CC systems, and lysosomal storage. {ECO:0000269|PubMed:12189593,
CC ECO:0000269|PubMed:12812989}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the sterol desaturase 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; D85181; BAA18970.1; -; mRNA.
DR EMBL; AF187981; AAF00544.1; -; mRNA.
DR EMBL; AB016247; BAA33729.1; -; mRNA.
DR EMBL; AB057650; BAB68218.1; -; Genomic_DNA.
DR EMBL; AK312634; BAG35518.1; -; mRNA.
DR EMBL; AK222686; BAD96406.1; -; mRNA.
DR EMBL; AK223141; BAD96861.1; -; mRNA.
DR EMBL; CH471065; EAW67520.1; -; Genomic_DNA.
DR EMBL; BC012333; AAH12333.1; -; mRNA.
DR EMBL; BC050427; AAH50427.1; -; mRNA.
DR CCDS; CCDS8435.1; -.
DR RefSeq; NP_001020127.1; NM_001024956.2.
DR RefSeq; NP_008849.2; NM_006918.4.
DR AlphaFoldDB; O75845; -.
DR BioGRID; 112216; 49.
DR IntAct; O75845; 12.
DR MINT; O75845; -.
DR STRING; 9606.ENSP00000264027; -.
DR ChEMBL; CHEMBL3509588; -.
DR SwissLipids; SLP:000001259; -.
DR iPTMnet; O75845; -.
DR PhosphoSitePlus; O75845; -.
DR SwissPalm; O75845; -.
DR BioMuta; SC5D; -.
DR EPD; O75845; -.
DR jPOST; O75845; -.
DR MassIVE; O75845; -.
DR PaxDb; O75845; -.
DR PeptideAtlas; O75845; -.
DR PRIDE; O75845; -.
DR ProteomicsDB; 50227; -.
DR TopDownProteomics; O75845; -.
DR Antibodypedia; 45921; 34 antibodies from 14 providers.
DR DNASU; 6309; -.
DR Ensembl; ENST00000264027.9; ENSP00000264027.4; ENSG00000109929.10.
DR Ensembl; ENST00000392789.2; ENSP00000376539.2; ENSG00000109929.10.
DR GeneID; 6309; -.
DR KEGG; hsa:6309; -.
DR MANE-Select; ENST00000264027.9; ENSP00000264027.4; NM_006918.5; NP_008849.2.
DR UCSC; uc001pxu.4; human.
DR CTD; 6309; -.
DR DisGeNET; 6309; -.
DR GeneCards; SC5D; -.
DR HGNC; HGNC:10547; SC5D.
DR HPA; ENSG00000109929; Tissue enhanced (liver).
DR MalaCards; SC5D; -.
DR MIM; 602286; gene.
DR MIM; 607330; phenotype.
DR neXtProt; NX_O75845; -.
DR OpenTargets; ENSG00000109929; -.
DR Orphanet; 46059; Lathosterolosis.
DR PharmGKB; PA34957; -.
DR VEuPathDB; HostDB:ENSG00000109929; -.
DR eggNOG; KOG0872; Eukaryota.
DR GeneTree; ENSGT00550000075101; -.
DR InParanoid; O75845; -.
DR OMA; HTLHHMY; -.
DR OrthoDB; 1249774at2759; -.
DR PhylomeDB; O75845; -.
DR TreeFam; TF300797; -.
DR BioCyc; MetaCyc:HS03271-MON; -.
DR BRENDA; 1.14.19.20; 2681.
DR PathwayCommons; O75845; -.
DR Reactome; R-HSA-2426168; Activation of gene expression by SREBF (SREBP).
DR Reactome; R-HSA-6807047; Cholesterol biosynthesis via desmosterol.
DR Reactome; R-HSA-6807062; Cholesterol biosynthesis via lathosterol.
DR SignaLink; O75845; -.
DR BioGRID-ORCS; 6309; 21 hits in 1072 CRISPR screens.
DR ChiTaRS; SC5D; human.
DR GeneWiki; Sterol-C5-desaturase-like; -.
DR GenomeRNAi; 6309; -.
DR Pharos; O75845; Tbio.
DR PRO; PR:O75845; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; O75845; protein.
DR Bgee; ENSG00000109929; Expressed in adrenal tissue and 205 other tissues.
DR ExpressionAtlas; O75845; baseline and differential.
DR Genevisible; O75845; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0000248; F:C-5 sterol desaturase activity; EXP:Reactome.
DR GO; GO:0050046; F:delta7-sterol 5(6)-desaturase activity; IEA:UniProtKB-EC.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0033489; P:cholesterol biosynthetic process via desmosterol; TAS:Reactome.
DR GO; GO:0033490; P:cholesterol biosynthetic process via lathosterol; IBA:GO_Central.
DR GO; GO:0006629; P:lipid metabolic process; TAS:ProtInc.
DR GO; GO:0016126; P:sterol biosynthetic process; IBA:GO_Central.
DR InterPro; IPR006694; Fatty_acid_hydroxylase.
DR Pfam; PF04116; FA_hydroxylase; 1.
PE 1: Evidence at protein level;
KW Disease variant; Endoplasmic reticulum; Iron; Lipid biosynthesis;
KW Lipid metabolism; Membrane; Oxidoreductase; Phosphoprotein;
KW Reference proteome; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..299
FT /note="Lathosterol oxidase"
FT /id="PRO_0000117028"
FT TRANSMEM 32..52
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 79..99
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 117..137
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 186..206
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 124..252
FT /note="Fatty acid hydroxylase"
FT /evidence="ECO:0000255"
FT REGION 274..299
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 138..143
FT /note="Histidine box-1"
FT MOTIF 151..155
FT /note="Histidine box-2"
FT MOTIF 228..233
FT /note="Histidine box-3"
FT MOD_RES 253
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT VARIANT 29
FT /note="R -> Q (in LATHOS; dbSNP:rs104894295)"
FT /evidence="ECO:0000269|PubMed:12189593"
FT /id="VAR_014423"
FT VARIANT 46
FT /note="Y -> S (in LATHOS; dbSNP:rs104894297)"
FT /evidence="ECO:0000269|PubMed:12812989"
FT /id="VAR_020829"
FT VARIANT 211
FT /note="G -> D (in LATHOS; dbSNP:rs104894296)"
FT /evidence="ECO:0000269|PubMed:12189593"
FT /id="VAR_014424"
FT CONFLICT 216..299
FT /note="PQILQPFINGSAHHTDHHMFFDYNYGQYFTLWDRIGGSFKNPSSFEGKGPLS
FT YVKEMTEGKRSSHSGNGCKNEKLFNGEFTKTE -> RMKNYSMESLQRLNRLLPSYS
FT (in Ref. 1; BAA18970)"
FT /evidence="ECO:0000305"
FT CONFLICT 280
FT /note="H -> P (in Ref. 3; BAA33729 and 4; BAB68218)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 299 AA; 35301 MW; 9EF8B20D522FAA56 CRC64;
MDLVLRVADY YFFTPYVYPA TWPEDDIFRQ AISLLIVTNV GAYILYFFCA TLSYYFVFDH
ALMKHPQFLK NQVRREIKFT VQALPWISIL TVALFLLEIR GYSKLHDDLG EFPYGLFELV
VSIISFLFFT DMFIYWIHRG LHHRLVYKRL HKPHHIWKIP TPFASHAFHP IDGFLQSLPY
HIYPFIFPLH KVVYLSLYIL VNIWTISIHD GDFRVPQILQ PFINGSAHHT DHHMFFDYNY
GQYFTLWDRI GGSFKNPSSF EGKGPLSYVK EMTEGKRSSH SGNGCKNEKL FNGEFTKTE
