MSMO1_HUMAN
ID MSMO1_HUMAN Reviewed; 293 AA.
AC Q15800; A8K8Q3; A8MYF6; D3DP32; Q32Q24;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 186.
DE RecName: Full=Methylsterol monooxygenase 1 {ECO:0000303|PubMed:23583456};
DE EC=1.14.18.9 {ECO:0000250|UniProtKB:O35532};
DE AltName: Full=C-4 methylsterol oxidase {ECO:0000303|PubMed:23583456};
DE AltName: Full=Sterol-C4-methyl oxidase {ECO:0000303|PubMed:21285510};
GN Name=MSMO1; Synonyms=DESP4, ERG25, SC4MOL;
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] (ISOFORM 1), AND COFACTOR.
RC TISSUE=Intestine;
RX PubMed=8663358; DOI=10.1074/jbc.271.28.16927;
RA Li L., Kaplan J.;
RT "Characterization of yeast methyl sterol oxidase (ERG25) and identification
RT of a human homologue.";
RL J. Biol. Chem. 271:16927-16933(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Retina;
RA Herrmann K.;
RL Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Corpus callosum, and Testis;
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15815621; DOI=10.1038/nature03466;
RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P.,
RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C.,
RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L.,
RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A.,
RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J.,
RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M.,
RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T.,
RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S.,
RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K.,
RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C.,
RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S.,
RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C.,
RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M.,
RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C.,
RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J.,
RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X.,
RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M.,
RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C.,
RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S.,
RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H.,
RA Wilson R.K.;
RT "Generation and annotation of the DNA sequences of human chromosomes 2 and
RT 4.";
RL Nature 434:724-731(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Eye;
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 [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [8]
RP FUNCTION, AND PATHWAY.
RX PubMed=23583456; DOI=10.1016/j.bcp.2013.03.021;
RA Mazein A., Watterson S., Hsieh W.Y., Griffiths W.J., Ghazal P.;
RT "A comprehensive machine-readable view of the mammalian cholesterol
RT biosynthesis pathway.";
RL Biochem. Pharmacol. 86:56-66(2013).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=26114596; DOI=10.7554/elife.07999;
RA Mitsche M.A., McDonald J.G., Hobbs H.H., Cohen J.C.;
RT "Flux analysis of cholesterol biosynthesis in vivo reveals multiple tissue
RT and cell-type specific pathways.";
RL Elife 4:E07999-E07999(2015).
RN [11]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=26038696; DOI=10.1002/prp2.120;
RA Yasuda K., Iwanaga Y., Ogawa K., Mano H., Ueno S., Kimoto S., Ohta M.,
RA Kamakura M., Ikushiro S., Sakaki T.;
RT "Human hepatic metabolism of the anti-osteoporosis drug eldecalcitol
RT involves sterol C4-methyl oxidase.";
RL Pharmacol. Res. Perspect. 3:e00120-e00120(2015).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=28673550; DOI=10.1016/j.ymgme.2017.06.013;
RA Frisso G., Gelzo M., Procopio E., Sica C., Lenza M.P., Dello Russo A.,
RA Donati M.A., Salvatore F., Corso G.;
RT "A rare case of sterol-C4-methyl oxidase deficiency in a young Italian
RT male: Biochemical and molecular characterization.";
RL Mol. Genet. Metab. 121:329-335(2017).
RN [13]
RP INVOLVEMENT IN MCCPD, VARIANTS MCCPD GLN-173 AND CYS-244, FUNCTION,
RP CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=21285510; DOI=10.1172/jci42650;
RA He M., Kratz L.E., Michel J.J., Vallejo A.N., Ferris L., Kelley R.I.,
RA Hoover J.J., Jukic D., Gibson K.M., Wolfe L.A., Ramachandran D.,
RA Zwick M.E., Vockley J.;
RT "Mutations in the human SC4MOL gene encoding a methyl sterol oxidase cause
RT psoriasiform dermatitis, microcephaly, and developmental delay.";
RL J. Clin. Invest. 121:976-984(2011).
RN [14]
RP VARIANT MCCPD ARG-115.
RX PubMed=24144731; DOI=10.1016/j.bbalip.2013.10.009;
RA He M., Smith L.D., Chang R., Li X., Vockley J.;
RT "The role of sterol-C4-methyl oxidase in epidermal biology.";
RL Biochim. Biophys. Acta 1841:331-335(2014).
CC -!- FUNCTION: Catalyzes the three-step monooxygenation required for the
CC demethylation of 4,4-dimethyl and 4alpha-methylsterols, which can be
CC subsequently metabolized to cholesterol (PubMed:21285510,
CC PubMed:28673550, PubMed:23583456, PubMed:26114596). Also involved in
CC drug metabolism, as it can metabolize eldecalcitol (ED-71 or 1alpha,25-
CC dihydroxy-2beta-(3-hydroxypropoxy)-cholecalciferol), a second-
CC generation vitamin D analog, into 1alpha,2beta,25-trihydroxy vitamin
CC D3; this reaction occurs via enzymatic hydroxylation and spontaneous O-
CC dehydroxypropylation (PubMed:26038696). {ECO:0000269|PubMed:21285510,
CC ECO:0000269|PubMed:26038696, ECO:0000269|PubMed:28673550,
CC ECO:0000305|PubMed:23583456, ECO:0000305|PubMed:26114596}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4,4-dimethyl-5alpha-cholest-7-en-3beta-ol + 6 Fe(II)-
CC [cytochrome b5] + 5 H(+) + 3 O2 = 4alpha-carboxy-4beta-methyl-5alpha-
CC cholest-7-ene-3beta-ol + 6 Fe(III)-[cytochrome b5] + 4 H2O;
CC Xref=Rhea:RHEA:55220, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16455, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034,
CC ChEBI:CHEBI:58387; EC=1.14.18.9;
CC Evidence={ECO:0000250|UniProtKB:O35532};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55221;
CC Evidence={ECO:0000250|UniProtKB:O35532};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + 6 Fe(II)-
CC [cytochrome b5] + 5 H(+) + 3 O2 = 4beta-methylzymosterol-4alpha-
CC carboxylate + 6 Fe(III)-[cytochrome b5] + 4 H2O;
CC Xref=Rhea:RHEA:55244, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:18364, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034,
CC ChEBI:CHEBI:64925; Evidence={ECO:0000269|PubMed:21285510,
CC ECO:0000269|PubMed:28673550, ECO:0000305|PubMed:26114596};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55245;
CC Evidence={ECO:0000269|PubMed:21285510, ECO:0000269|PubMed:28673550,
CC ECO:0000305|PubMed:26114596};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4alpha-methylzymosterol + 6 Fe(II)-[cytochrome b5] + 5 H(+) +
CC 3 O2 = 4alpha-carboxyzymosterol + 6 Fe(III)-[cytochrome b5] + 4 H2O;
CC Xref=Rhea:RHEA:47056, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439,
CC ChEBI:CHEBI:1949, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034,
CC ChEBI:CHEBI:143575; Evidence={ECO:0000305|PubMed:21285510,
CC ECO:0000305|PubMed:26114596, ECO:0000305|PubMed:28673550};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47057;
CC Evidence={ECO:0000305|PubMed:21285510, ECO:0000305|PubMed:26114596,
CC ECO:0000305|PubMed:28673550};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4alpha-methyl-5alpha-cholest-7-en-3beta-ol + 6 Fe(II)-
CC [cytochrome b5] + 5 H(+) + 3 O2 = 4alpha-carboxy-5alpha-cholest-7-en-
CC 3beta-ol + 6 Fe(III)-[cytochrome b5] + 4 H2O; Xref=Rhea:RHEA:62768,
CC Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:18378,
CC ChEBI:CHEBI:29033, ChEBI:CHEBI:29034, ChEBI:CHEBI:145943;
CC Evidence={ECO:0000269|PubMed:21285510, ECO:0000269|PubMed:28673550};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62769;
CC Evidence={ECO:0000269|PubMed:21285510, ECO:0000269|PubMed:28673550};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4,4-dimethyl-5alpha-cholest-8-en-3beta-ol + 6 Fe(II)-
CC [cytochrome b5] + 5 H(+) + 3 O2 = 4alpha-carboxy-4beta-methyl-5alpha-
CC cholest-8-en-3beta-ol + 6 Fe(III)-[cytochrome b5] + 4 H2O;
CC Xref=Rhea:RHEA:62776, 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:87044,
CC ChEBI:CHEBI:87047; Evidence={ECO:0000269|PubMed:21285510,
CC ECO:0000269|PubMed:28673550};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62777;
CC Evidence={ECO:0000269|PubMed:21285510, ECO:0000269|PubMed:28673550};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=4alpha-methyl-5alpha-cholest-8-en-3beta-ol + 6 Fe(II)-
CC [cytochrome b5] + 5 H(+) + 3 O2 = 4alpha-carboxy-5alpha-cholest-8-
CC ene-3beta-ol + 6 Fe(III)-[cytochrome b5] + 4 H2O;
CC Xref=Rhea:RHEA:62780, 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:87051,
CC ChEBI:CHEBI:87055; Evidence={ECO:0000269|PubMed:21285510,
CC ECO:0000269|PubMed:28673550};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62781;
CC Evidence={ECO:0000269|PubMed:21285510, ECO:0000269|PubMed:28673550};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)-cholecalciferol +
CC 2 Fe(II)-[cytochrome b5] + 2 H(+) + O2 = 1alpha,25-dihydroxy-2beta-
CC (1,3-dihydroxypropoxy)-cholecalciferol + 2 Fe(III)-[cytochrome b5] +
CC H2O; Xref=Rhea:RHEA:62820, Rhea:RHEA-COMP:10438, Rhea:RHEA-
CC COMP:10439, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:29033, ChEBI:CHEBI:29034, ChEBI:CHEBI:73927,
CC ChEBI:CHEBI:146141; Evidence={ECO:0000269|PubMed:26038696};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62821;
CC Evidence={ECO:0000269|PubMed:26038696};
CC -!- COFACTOR:
CC Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC Evidence={ECO:0000305|PubMed:8663358};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=19.5 uM for 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)-
CC cholecalciferol {ECO:0000269|PubMed:26038696};
CC Vmax=19 pmol/min/mg enzyme with 1alpha,25-dihydroxy-2beta-(3-
CC hydroxypropoxy)-cholecalciferol as substrate
CC {ECO:0000269|PubMed:26038696};
CC -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from
CC lanosterol: step 3/6. {ECO:0000305|PubMed:23583456,
CC ECO:0000305|PubMed:26114596}.
CC -!- PATHWAY: Steroid biosynthesis; cholesterol biosynthesis.
CC {ECO:0000305|PubMed:21285510, ECO:0000305|PubMed:23583456,
CC ECO:0000305|PubMed:26114596, ECO:0000305|PubMed:28673550}.
CC -!- INTERACTION:
CC Q15800; Q6NT55: CYP4F22; NbExp=3; IntAct=EBI-949102, EBI-17509525;
CC Q15800; Q96LL9: DNAJC30; NbExp=3; IntAct=EBI-949102, EBI-8639143;
CC Q15800; Q9UKR5: ERG28; NbExp=3; IntAct=EBI-949102, EBI-711490;
CC Q15800; Q6ZVE7: GOLT1A; NbExp=3; IntAct=EBI-949102, EBI-17231387;
CC Q15800; P09601: HMOX1; NbExp=3; IntAct=EBI-949102, EBI-2806151;
CC Q15800; P50281: MMP14; NbExp=3; IntAct=EBI-949102, EBI-992788;
CC Q15800; P0DN84: STRIT1; NbExp=3; IntAct=EBI-949102, EBI-12200293;
CC Q15800; Q13277: STX3; NbExp=3; IntAct=EBI-949102, EBI-1394295;
CC Q15800; P17152: TMEM11; NbExp=3; IntAct=EBI-949102, EBI-723946;
CC Q15800; Q9NV12: TMEM140; NbExp=3; IntAct=EBI-949102, EBI-2844246;
CC Q15800; Q9NWH2: TMEM242; NbExp=3; IntAct=EBI-949102, EBI-10315004;
CC Q15800; Q6PI78: TMEM65; NbExp=3; IntAct=EBI-949102, EBI-6656213;
CC Q15800; Q8N661: TMEM86B; NbExp=3; IntAct=EBI-949102, EBI-2548832;
CC Q15800; O95070: YIF1A; NbExp=3; IntAct=EBI-949102, EBI-2799703;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q15800-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q15800-2; Sequence=VSP_044585;
CC -!- DOMAIN: The histidine box domains may contain the active site and/or be
CC involved in metal ion binding.
CC -!- DISEASE: Microcephaly, congenital cataract, and psoriasiform dermatitis
CC (MCCPD) [MIM:616834]: An autosomal recessive inborn error of
CC cholesterol metabolism characterized by accumulation of a large amount
CC of methylsterols, particularly dimethylsterols, in affected
CC individuals. Patients manifest psoriasiform dermatitis, arthralgias,
CC congenital cataracts, microcephaly, and developmental delay.
CC {ECO:0000269|PubMed:21285510, ECO:0000269|PubMed:24144731}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the sterol desaturase family. {ECO:0000305}.
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DR EMBL; U60205; AAC50587.1; -; mRNA.
DR EMBL; U93162; AAB81566.1; -; mRNA.
DR EMBL; AK292418; BAF85107.1; -; mRNA.
DR EMBL; AK295432; BAH12066.1; -; mRNA.
DR EMBL; AC012504; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471056; EAX04820.1; -; Genomic_DNA.
DR EMBL; CH471056; EAX04821.1; -; Genomic_DNA.
DR EMBL; BC010653; AAH10653.1; -; mRNA.
DR EMBL; BC107879; AAI07880.1; -; mRNA.
DR CCDS; CCDS3809.1; -. [Q15800-1]
DR CCDS; CCDS43280.1; -. [Q15800-2]
DR RefSeq; NP_001017369.1; NM_001017369.2. [Q15800-2]
DR RefSeq; NP_006736.1; NM_006745.4. [Q15800-1]
DR RefSeq; XP_005263233.1; XM_005263176.2. [Q15800-1]
DR AlphaFoldDB; Q15800; -.
DR BioGRID; 112214; 94.
DR IntAct; Q15800; 25.
DR MINT; Q15800; -.
DR STRING; 9606.ENSP00000261507; -.
DR DrugBank; DB00157; NADH.
DR SwissLipids; SLP:000001244; -.
DR GlyGen; Q15800; 2 sites.
DR iPTMnet; Q15800; -.
DR PhosphoSitePlus; Q15800; -.
DR SwissPalm; Q15800; -.
DR BioMuta; MSMO1; -.
DR DMDM; 2498340; -.
DR EPD; Q15800; -.
DR jPOST; Q15800; -.
DR MassIVE; Q15800; -.
DR MaxQB; Q15800; -.
DR PaxDb; Q15800; -.
DR PeptideAtlas; Q15800; -.
DR PRIDE; Q15800; -.
DR ProteomicsDB; 2398; -.
DR ProteomicsDB; 60767; -. [Q15800-1]
DR Antibodypedia; 28315; 132 antibodies from 19 providers.
DR DNASU; 6307; -.
DR Ensembl; ENST00000261507.11; ENSP00000261507.6; ENSG00000052802.13. [Q15800-1]
DR Ensembl; ENST00000393766.6; ENSP00000377361.2; ENSG00000052802.13. [Q15800-2]
DR GeneID; 6307; -.
DR KEGG; hsa:6307; -.
DR MANE-Select; ENST00000261507.11; ENSP00000261507.6; NM_006745.5; NP_006736.1.
DR UCSC; uc003ire.4; human. [Q15800-1]
DR CTD; 6307; -.
DR DisGeNET; 6307; -.
DR GeneCards; MSMO1; -.
DR HGNC; HGNC:10545; MSMO1.
DR HPA; ENSG00000052802; Tissue enhanced (liver).
DR MalaCards; MSMO1; -.
DR MIM; 607545; gene.
DR MIM; 616834; phenotype.
DR neXtProt; NX_Q15800; -.
DR OpenTargets; ENSG00000052802; -.
DR Orphanet; 488168; Microcephaly-congenital cataract-psoriasiform dermatitis syndrome.
DR PharmGKB; PA34955; -.
DR VEuPathDB; HostDB:ENSG00000052802; -.
DR eggNOG; KOG0873; Eukaryota.
DR GeneTree; ENSGT00940000158012; -.
DR HOGENOM; CLU_047036_5_3_1; -.
DR InParanoid; Q15800; -.
DR OMA; IVHEFIY; -.
DR OrthoDB; 1493916at2759; -.
DR PhylomeDB; Q15800; -.
DR TreeFam; TF354294; -.
DR BioCyc; MetaCyc:HS00650-MON; -.
DR BRENDA; 1.14.18.9; 2681.
DR PathwayCommons; Q15800; -.
DR Reactome; R-HSA-191273; Cholesterol biosynthesis.
DR SignaLink; Q15800; -.
DR UniPathway; UPA00063; -.
DR UniPathway; UPA00770; UER00756.
DR BioGRID-ORCS; 6307; 30 hits in 1079 CRISPR screens.
DR ChiTaRS; MSMO1; human.
DR GenomeRNAi; 6307; -.
DR Pharos; Q15800; Tbio.
DR PRO; PR:Q15800; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q15800; protein.
DR Bgee; ENSG00000052802; Expressed in adrenal tissue and 211 other tissues.
DR ExpressionAtlas; Q15800; baseline and differential.
DR Genevisible; Q15800; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; TAS:ProtInc.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc.
DR GO; GO:0016020; C:membrane; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; TAS:ProtInc.
DR GO; GO:0000254; F:C-4 methylsterol oxidase activity; IBA:GO_Central.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0006695; P:cholesterol biosynthetic process; TAS:Reactome.
DR GO; GO:0006631; P:fatty acid metabolic process; TAS:ProtInc.
DR GO; GO:0008202; P:steroid 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 Alternative splicing; Cataract; Cholesterol biosynthesis;
KW Cholesterol metabolism; Disease variant; Endoplasmic reticulum; Iron;
KW Lipid biosynthesis; Lipid metabolism; Membrane; NAD; Oxidoreductase;
KW Reference proteome; Steroid biosynthesis; Steroid metabolism;
KW Sterol biosynthesis; Sterol metabolism; Transmembrane; Transmembrane helix.
FT CHAIN 1..293
FT /note="Methylsterol monooxygenase 1"
FT /id="PRO_0000117033"
FT TRANSMEM 55..75
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 100..120
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 199..219
FT /note="Helical"
FT /evidence="ECO:0000255"
FT DOMAIN 145..274
FT /note="Fatty acid hydroxylase"
FT /evidence="ECO:0000255"
FT MOTIF 157..161
FT /note="Histidine box-1"
FT MOTIF 170..174
FT /note="Histidine box-2"
FT MOTIF 249..255
FT /note="Histidine box-3"
FT VAR_SEQ 1..131
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044585"
FT VARIANT 115
FT /note="G -> R (in MCCPD; unknown pathological significance;
FT dbSNP:rs1310714454)"
FT /evidence="ECO:0000269|PubMed:24144731"
FT /id="VAR_076531"
FT VARIANT 124
FT /note="N -> S (in dbSNP:rs34499452)"
FT /id="VAR_048898"
FT VARIANT 173
FT /note="H -> Q (in MCCPD; dbSNP:rs869025576)"
FT /evidence="ECO:0000269|PubMed:21285510"
FT /id="VAR_076532"
FT VARIANT 244
FT /note="Y -> C (in MCCPD; dbSNP:rs760048191)"
FT /evidence="ECO:0000269|PubMed:21285510"
FT /id="VAR_076533"
SQ SEQUENCE 293 AA; 35216 MW; D88E0DDBE85DE0BF CRC64;
MATNESVSIF SSASLAVEYV DSLLPENPLQ EPFKNAWNYM LNNYTKFQIA TWGSLIVHEA
LYFLFCLPGF LFQFIPYMKK YKIQKDKPET WENQWKCFKV LLFNHFCIQL PLICGTYYFT
EYFNIPYDWE RMPRWYFLLA RCFGCAVIED TWHYFLHRLL HHKRIYKYIH KVHHEFQAPF
GMEAEYAHPL ETLILGTGFF IGIVLLCDHV ILLWAWVTIR LLETIDVHSG YDIPLNPLNL
IPFYAGSRHH DFHHMNFIGN YASTFTWWDR IFGTDSQYNA YNEKRKKFEK KTE
