ID   SC5D_RAT                Reviewed;         299 AA.
AC   Q9EQS5;
DT   14-OCT-2015, integrated into UniProtKB/Swiss-Prot.
DT   01-MAR-2001, sequence version 1.
DT   27-MAR-2024, entry version 137.
DE   RecName: Full=Lathosterol oxidase;
DE            EC=1.14.19.20;
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 {ECO:0000312|EMBL:BAB19798.1};
GN   Name=Sc5d {ECO:0000312|RGD:620775};
GN   Synonyms=C5d {ECO:0000312|EMBL:BAB19798.1};
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Sprague-Dawley; TISSUE=Liver;
RA   Nishino H., Hozumi K., Moromi M., Nam S., Ishibashi T.;
RT   "Cloning, expression, and site-directed mutagenesis of the mammalian sterol
RT   C5-desaturase.";
RL   Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Brown Norway;
RX   PubMed=15057822; DOI=10.1038/nature02426;
RA   Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA   Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA   Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA   Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA   Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA   Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA   Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA   Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA   Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA   Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA   Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA   Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA   Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA   Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA   Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA   Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA   Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA   Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA   Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA   Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA   Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA   Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA   Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA   Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA   Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA   Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA   Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA   Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA   Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA   Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA   Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA   Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA   Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA   Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA   Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA   Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA   Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA   Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA   Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA   Mockrin S., Collins F.S.;
RT   "Genome sequence of the Brown Norway rat yields insights into mammalian
RT   evolution.";
RL   Nature 428:493-521(2004).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Testis {ECO:0000312|EMBL:AAH81704.1};
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   [5]
RP   FUNCTION, SUBCELLULAR LOCATION, AND CATALYTIC ACTIVITY.
RX   PubMed=4019441; DOI=10.1093/oxfordjournals.jbchem.a135137;
RA   Honjo K., Ishibashi T., Imai Y.;
RT   "Partial purification and characterization of lathosterol 5-desaturase from
RT   rat liver microsomes.";
RL   J. Biochem. 97:955-959(1985).
RN   [6]
RP   CATALYTIC ACTIVITY.
RX   PubMed=9056262; DOI=10.1006/abbi.1996.9871;
RA   Nishino H., Nakaya J., Nishi S., Kurosawa T., Ishibashi T.;
RT   "Temperature-induced differential kinetic properties between an initial
RT   burst and the following steady state in membrane-bound enzymes: studies on
RT   lathosterol 5-desaturase.";
RL   Arch. Biochem. Biophys. 339:298-304(1997).
CC   -!- FUNCTION: Catalyzes a dehydrogenation to introduce C5-6 double bond
CC       into lathosterol in cholesterol biosynthesis.
CC       {ECO:0000269|PubMed:4019441}.
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:0000269|PubMed:4019441, ECO:0000269|PubMed:9056262};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54321;
CC         Evidence={ECO:0000305|PubMed:4019441, ECO:0000305|PubMed:9056262};
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:0000250|UniProtKB:O75845};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46557;
CC         Evidence={ECO:0000250|UniProtKB:O75845};
CC   -!- COFACTOR:
CC       Name=Fe cation; Xref=ChEBI:CHEBI:24875; Evidence={ECO:0000250};
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000305|PubMed:4019441}; Multi-pass membrane protein
CC       {ECO:0000305}.
CC   -!- DOMAIN: The histidine box domains may contain the active site and/or be
CC       involved in metal ion binding.
CC   -!- SIMILARITY: Belongs to the sterol desaturase family. {ECO:0000305}.
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DR   EMBL; AB052846; BAB19798.1; -; mRNA.
DR   EMBL; AC133265; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH473975; EDL95251.1; -; Genomic_DNA.
DR   EMBL; BC081704; AAH81704.1; -; mRNA.
DR   RefSeq; NP_446094.1; NM_053642.2.
DR   RefSeq; XP_017450895.1; XM_017595406.1.
DR   AlphaFoldDB; Q9EQS5; -.
DR   STRING; 10116.ENSRNOP00000011284; -.
DR   PhosphoSitePlus; Q9EQS5; -.
DR   PaxDb; 10116-ENSRNOP00000011284; -.
DR   Ensembl; ENSRNOT00000106582.1; ENSRNOP00000092291.1; ENSRNOG00000065944.1.
DR   Ensembl; ENSRNOT00055032323; ENSRNOP00055026149; ENSRNOG00055018957.
DR   Ensembl; ENSRNOT00060032362; ENSRNOP00060026373; ENSRNOG00060018782.
DR   Ensembl; ENSRNOT00065039699; ENSRNOP00065032289; ENSRNOG00065023232.
DR   GeneID; 114100; -.
DR   KEGG; rno:114100; -.
DR   UCSC; RGD:620775; rat.
DR   AGR; RGD:620775; -.
DR   CTD; 6309; -.
DR   RGD; 620775; Sc5d.
DR   eggNOG; KOG0872; Eukaryota.
DR   GeneTree; ENSGT00550000075101; -.
DR   HOGENOM; CLU_047036_2_2_1; -.
DR   InParanoid; Q9EQS5; -.
DR   OMA; FVFICPM; -.
DR   OrthoDB; 531at2759; -.
DR   PhylomeDB; Q9EQS5; -.
DR   TreeFam; TF300797; -.
DR   Reactome; R-RNO-6807047; Cholesterol biosynthesis via desmosterol.
DR   Reactome; R-RNO-6807062; Cholesterol biosynthesis via lathosterol.
DR   PRO; PR:Q9EQS5; -.
DR   Proteomes; UP000002494; Chromosome 8.
DR   Proteomes; UP000234681; Chromosome 8.
DR   Bgee; ENSRNOG00000008305; Expressed in liver and 20 other cell types or tissues.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0016020; C:membrane; IBA:GO_Central.
DR   GO; GO:0000248; F:C-5 sterol desaturase activity; IDA:RGD.
DR   GO; GO:0050046; F:delta7-sterol 5(6)-desaturase activity; TAS:RGD.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0033490; P:cholesterol biosynthetic process via lathosterol; IDA:RGD.
DR   GO; GO:0006631; P:fatty acid metabolic process; TAS:RGD.
DR   InterPro; IPR006694; Fatty_acid_hydroxylase.
DR   PANTHER; PTHR11863:SF226; LATHOSTEROL OXIDASE-RELATED; 1.
DR   PANTHER; PTHR11863; STEROL DESATURASE; 1.
DR   Pfam; PF04116; FA_hydroxylase; 1.
DR   Genevisible; Q9EQS5; RN.
PE   1: Evidence at protein level;
KW   Endoplasmic reticulum; Iron; Lipid biosynthesis; Lipid metabolism;
KW   Membrane; Oxidoreductase; Phosphoprotein; Reference proteome;
KW   Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW   Sterol metabolism; Transmembrane; Transmembrane helix.
FT   CHAIN           1..299
FT                   /note="Lathosterol oxidase"
FT                   /id="PRO_0000434558"
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   DOMAIN          124..252
FT                   /note="Fatty acid hydroxylase"
FT                   /evidence="ECO:0000255"
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:0000250|UniProtKB:O75845"
SQ   SEQUENCE   299 AA;  35147 MW;  AE2D03FF486A46A3 CRC64;
     MDLVLSAADY YFFTPYVYPA TWPEDNIIRQ TVSLLVVTNL GAYILYFFCA TLSYYFVYDH
     SLMKHPQFLK NQVSREIMFT VKSLPWISIP TVSLFLLELR GYSKLYDDIG DFPNGWIHLI
     MSVISFLFFT DMLIYWIHRG LHHRLLYKHI HKPHHIWKIP TPFASHAFHP VDGFLQSLPY
     HIYPFVFPLH KVVYLGLYVL VNVWTISIHD GDFRVPQIFR PFINGSAHHT DHHMLFDYNY
     GQYFTLWDRI GGSFKHPSSF EGKGPHSYVK NMTEKESNSL AENGCKSKKL CNGEFTKNE
//