CP51A_HUMAN
ID CP51A_HUMAN Reviewed; 509 AA.
AC Q16850; A0A0C4DFL7; A4D1F8; B2RAI4; B4DJ55; O00770; O00772; Q16784; Q8N1A8;
AC Q99868;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 29-SEP-2021, sequence version 4.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=Lanosterol 14-alpha demethylase {ECO:0000305};
DE Short=LDM;
DE EC=1.14.14.154 {ECO:0000269|PubMed:20149798, ECO:0000269|PubMed:8619637};
DE AltName: Full=CYPLI;
DE AltName: Full=Cytochrome P450 51A1;
DE AltName: Full=Cytochrome P450-14DM;
DE Short=Cytochrome P45014DM;
DE AltName: Full=Cytochrome P450LI;
DE AltName: Full=Sterol 14-alpha demethylase;
GN Name=CYP51A1 {ECO:0000312|HGNC:HGNC:2649}; Synonyms=CYP51;
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), FUNCTION, CATALYTIC ACTIVITY, AND
RP TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=8619637; DOI=10.1006/abbi.1996.0193;
RA Stroemstedt M., Rozman D., Waterman M.R.;
RT "The ubiquitously expressed human CYP51 encodes lanosterol 14 alpha-
RT demethylase, a cytochrome P450 whose expression is regulated by
RT oxysterols.";
RL Arch. Biochem. Biophys. 329:73-81(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=8797093; DOI=10.1093/oxfordjournals.jbchem.a021331;
RA Aoyama Y., Noshiro M., Gotoh O., Imaoka S., Funae Y., Kurosawa N.,
RA Horiuchi T., Yoshida Y.;
RT "Sterol 14-demethylase P450 (P45014DM*) is one of the most ancient and
RT conserved P450 species.";
RL J. Biochem. 119:926-933(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Liver;
RX PubMed=8809088; DOI=10.1006/abbi.1996.0416;
RA Rozman D., Stroemstedt M., Waterman M.R.;
RT "The three human cytochrome P450 lanosterol 14 alpha-demethylase (CYP51)
RT genes reside on chromosomes 3, 7, and 13: structure of the two
RT retrotransposed pseudogenes, association with a line-1 element, and
RT evolution of the human CYP51 family.";
RL Arch. Biochem. Biophys. 333:466-474(1996).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8975714; DOI=10.1006/geno.1996.0640;
RA Rozman D., Stroemstedt M., Tsui L.-C., Scherer S.W., Waterman M.R.;
RT "Structure and mapping of the human lanosterol 14alpha-demethylase gene
RT (CYP51) encoding the cytochrome P450 involved in cholesterol biosynthesis;
RT comparison of exon/intron organization with other mammalian and fungal CYP
RT genes.";
RL Genomics 38:371-381(1996).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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 GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S., Kwasnicka D.,
RA Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S.,
RA Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R.,
RA Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N.,
RA Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E.,
RA Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R.,
RA Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T.,
RA Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W.,
RA Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A.,
RA Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X.,
RA Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E.,
RA Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J.,
RA Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [8]
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 [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
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 [10]
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 [11]
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 [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 60-508 IN COMPLEXES WITH HEME;
RP KETOCONAZOLE AND ECONAZOLE, CATALYTIC ACTIVITY, FUNCTION, AND COFACTOR.
RX PubMed=20149798; DOI=10.1016/j.jmb.2010.01.075;
RA Strushkevich N., Usanov S.A., Park H.W.;
RT "Structural basis of human CYP51 inhibition by antifungal azoles.";
RL J. Mol. Biol. 397:1067-1078(2010).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in sterol
CC biosynthesis. Catalyzes 14-alpha demethylation of lanosterol and 24,25-
CC dihydrolanosterol likely through sequential oxidative conversion of 14-
CC alpha methyl group to hydroxymethyl, then to carboxylaldehyde, followed
CC by the formation of the delta 14,15 double bond in the sterol core and
CC concomitant release of formic acid (PubMed:20149798, PubMed:8619637).
CC Mechanistically, uses molecular oxygen inserting one oxygen atom into a
CC substrate, and reducing the second into a water molecule, with two
CC electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-
CC ferrihemoprotein reductase) (PubMed:20149798, PubMed:8619637).
CC {ECO:0000269|PubMed:20149798, ECO:0000269|PubMed:8619637}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 14alpha-methyl steroid + 3 O2 + 3 reduced [NADPH--
CC hemoprotein reductase] = a Delta(14) steroid + formate + 4 H(+) + 4
CC H2O + 3 oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:54028, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15740, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:138029, ChEBI:CHEBI:138031; EC=1.14.14.154;
CC Evidence={ECO:0000269|PubMed:20149798, ECO:0000269|PubMed:8619637};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:54029;
CC Evidence={ECO:0000305|PubMed:20149798, ECO:0000305|PubMed:8619637};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=lanosterol + 3 O2 + 3 reduced [NADPH--hemoprotein reductase] =
CC 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol + formate + 4
CC H(+) + 4 H2O + 3 oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:25286, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15740, ChEBI:CHEBI:16521, ChEBI:CHEBI:17813,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210; EC=1.14.14.154;
CC Evidence={ECO:0000269|PubMed:20149798};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:25287;
CC Evidence={ECO:0000305|PubMed:20149798};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=24,25-dihydrolanosterol + 3 O2 + 3 reduced [NADPH--hemoprotein
CC reductase] = 4,4-dimethyl-8,14-cholestadien-3beta-ol + formate + 4
CC H(+) + 4 H2O + 3 oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:45960, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:15740, ChEBI:CHEBI:28113, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:78904;
CC Evidence={ECO:0000269|PubMed:8619637};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:45961;
CC Evidence={ECO:0000305|PubMed:8619637};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000269|PubMed:20149798};
CC -!- ACTIVITY REGULATION: Inhibited by azalanstat. Inhibited by azole
CC antifungal agents ketoconazole, itraconazole and fluconazole.
CC {ECO:0000250|UniProtKB:Q64654}.
CC -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from
CC lanosterol: step 1/6. {ECO:0000305|PubMed:8619637}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:Q64654}; Single-pass membrane protein
CC {ECO:0000255}. Microsome membrane {ECO:0000250|UniProtKB:Q64654};
CC Single-pass membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q16850-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q16850-2; Sequence=VSP_037413;
CC -!- TISSUE SPECIFICITY: Ubiquitously expressed with highest levels in
CC testis, ovary, adrenal, prostate, liver, kidney and lung.
CC {ECO:0000269|PubMed:8619637}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-7 is the initiator.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC50951.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={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; U23942; AAB39951.1; -; mRNA.
DR EMBL; D55653; BAA09512.1; -; mRNA.
DR EMBL; U51692; AAC50951.1; ALT_INIT; Genomic_DNA.
DR EMBL; U51684; AAC50951.1; JOINED; Genomic_DNA.
DR EMBL; U51685; AAC50951.1; JOINED; Genomic_DNA.
DR EMBL; U51686; AAC50951.1; JOINED; Genomic_DNA.
DR EMBL; U51687; AAC50951.1; JOINED; Genomic_DNA.
DR EMBL; U51688; AAC50951.1; JOINED; Genomic_DNA.
DR EMBL; U51689; AAC50951.1; JOINED; Genomic_DNA.
DR EMBL; U51690; AAC50951.1; JOINED; Genomic_DNA.
DR EMBL; U51691; AAC50951.1; JOINED; Genomic_DNA.
DR EMBL; AK314205; BAG36881.1; -; mRNA.
DR EMBL; AK295932; BAG58717.1; -; mRNA.
DR EMBL; AC000120; AAB46356.1; -; Genomic_DNA.
DR EMBL; CH236949; EAL24154.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76858.1; -; Genomic_DNA.
DR EMBL; CH471091; EAW76859.1; -; Genomic_DNA.
DR EMBL; BC032322; AAH32322.1; -; mRNA.
DR CCDS; CCDS55123.1; -. [Q16850-2]
DR CCDS; CCDS5623.1; -. [Q16850-1]
DR PIR; JC4759; JC4759.
DR PIR; S68855; S68855.
DR RefSeq; NP_000777.1; NM_000786.3. [Q16850-1]
DR RefSeq; NP_001139624.1; NM_001146152.1. [Q16850-2]
DR PDB; 3JUS; X-ray; 2.90 A; A/B=60-508.
DR PDB; 3JUV; X-ray; 3.12 A; A=60-508.
DR PDB; 3LD6; X-ray; 2.80 A; A/B=60-508.
DR PDB; 4UHI; X-ray; 2.04 A; A/B/C/D=67-509.
DR PDB; 4UHL; X-ray; 2.50 A; A/B/C/D/E/F/G/H=67-509.
DR PDB; 6Q2T; X-ray; 2.80 A; A/B=67-509.
DR PDB; 6UEZ; X-ray; 1.98 A; A/B=67-509.
DR PDBsum; 3JUS; -.
DR PDBsum; 3JUV; -.
DR PDBsum; 3LD6; -.
DR PDBsum; 4UHI; -.
DR PDBsum; 4UHL; -.
DR PDBsum; 6Q2T; -.
DR PDBsum; 6UEZ; -.
DR AlphaFoldDB; Q16850; -.
DR SMR; Q16850; -.
DR BioGRID; 107967; 178.
DR IntAct; Q16850; 21.
DR MINT; Q16850; -.
DR STRING; 9606.ENSP00000003100; -.
DR BindingDB; Q16850; -.
DR ChEMBL; CHEMBL3849; -.
DR DrugBank; DB07705; (S)-econazole.
DR DrugBank; DB01167; Itraconazole.
DR DrugBank; DB05667; Levoketoconazole.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB01007; Tioconazole.
DR DrugCentral; Q16850; -.
DR GuidetoPHARMACOLOGY; 1374; -.
DR SwissLipids; SLP:000001162; -.
DR iPTMnet; Q16850; -.
DR PhosphoSitePlus; Q16850; -.
DR SwissPalm; Q16850; -.
DR BioMuta; CYP51A1; -.
DR DMDM; 3915660; -.
DR EPD; Q16850; -.
DR jPOST; Q16850; -.
DR MassIVE; Q16850; -.
DR MaxQB; Q16850; -.
DR PaxDb; Q16850; -.
DR PeptideAtlas; Q16850; -.
DR PRIDE; Q16850; -.
DR ProteomicsDB; 61101; -. [Q16850-1]
DR ProteomicsDB; 61102; -. [Q16850-2]
DR Antibodypedia; 34871; 275 antibodies from 30 providers.
DR DNASU; 1595; -.
DR Ensembl; ENST00000003100.13; ENSP00000003100.8; ENSG00000001630.18. [Q16850-1]
DR Ensembl; ENST00000450723.5; ENSP00000406757.1; ENSG00000001630.18. [Q16850-2]
DR GeneID; 1595; -.
DR KEGG; hsa:1595; -.
DR MANE-Select; ENST00000003100.13; ENSP00000003100.8; NM_000786.4; NP_000777.1.
DR UCSC; uc003ulm.5; human. [Q16850-1]
DR CTD; 1595; -.
DR DisGeNET; 1595; -.
DR GeneCards; CYP51A1; -.
DR HGNC; HGNC:2649; CYP51A1.
DR HPA; ENSG00000001630; Tissue enhanced (liver).
DR MalaCards; CYP51A1; -.
DR MIM; 601637; gene.
DR neXtProt; NX_Q16850; -.
DR OpenTargets; ENSG00000001630; -.
DR Orphanet; 521432; Congenital cataract-severe neonatal hepatopathy-global developmental delay syndrome.
DR PharmGKB; PA27123; -.
DR VEuPathDB; HostDB:ENSG00000001630; -.
DR eggNOG; KOG0684; Eukaryota.
DR GeneTree; ENSGT00930000151026; -.
DR HOGENOM; CLU_001570_15_0_1; -.
DR InParanoid; Q16850; -.
DR OMA; AWTLIEL; -.
DR OrthoDB; 572303at2759; -.
DR PhylomeDB; Q16850; -.
DR TreeFam; TF105091; -.
DR BioCyc; MetaCyc:HS00076-MON; -.
DR BRENDA; 1.14.13.70; 2681.
DR BRENDA; 1.14.14.154; 2681.
DR PathwayCommons; Q16850; -.
DR Reactome; R-HSA-191273; Cholesterol biosynthesis.
DR Reactome; R-HSA-211976; Endogenous sterols.
DR Reactome; R-HSA-2426168; Activation of gene expression by SREBF (SREBP).
DR Reactome; R-HSA-9619665; EGR2 and SOX10-mediated initiation of Schwann cell myelination.
DR SignaLink; Q16850; -.
DR UniPathway; UPA00770; UER00754.
DR BioGRID-ORCS; 1595; 20 hits in 1073 CRISPR screens.
DR ChiTaRS; CYP51A1; human.
DR EvolutionaryTrace; Q16850; -.
DR GenomeRNAi; 1595; -.
DR Pharos; Q16850; Tchem.
DR PRO; PR:Q16850; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q16850; protein.
DR Bgee; ENSG00000001630; Expressed in adrenal tissue and 105 other tissues.
DR ExpressionAtlas; Q16850; baseline and differential.
DR Genevisible; Q16850; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IDA:HPA.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0020037; F:heme binding; IDA:UniProtKB.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IBA:GO_Central.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0008398; F:sterol 14-demethylase activity; IDA:UniProtKB.
DR GO; GO:0006695; P:cholesterol biosynthetic process; TAS:Reactome.
DR GO; GO:1900222; P:negative regulation of amyloid-beta clearance; ISS:ARUK-UCL.
DR GO; GO:0042177; P:negative regulation of protein catabolic process; ISS:ARUK-UCL.
DR GO; GO:0050709; P:negative regulation of protein secretion; ISS:ARUK-UCL.
DR GO; GO:0006694; P:steroid biosynthetic process; IDA:UniProtKB.
DR GO; GO:0016125; P:sterol metabolic process; IBA:GO_Central.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cholesterol biosynthesis;
KW Cholesterol metabolism; Endoplasmic reticulum; Heme; Iron;
KW Lipid biosynthesis; Lipid metabolism; Membrane; Metal-binding; Microsome;
KW Monooxygenase; Oxidoreductase; Reference proteome; Steroid biosynthesis;
KW Steroid metabolism; Sterol biosynthesis; Sterol metabolism; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..509
FT /note="Lanosterol 14-alpha demethylase"
FT /id="PRO_0000051998"
FT TRANSMEM 30..50
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 455
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000269|PubMed:20149798"
FT VAR_SEQ 1..105
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_037413"
FT VARIANT 19
FT /note="V -> A (in dbSNP:rs2229188)"
FT /id="VAR_023470"
FT CONFLICT 276
FT /note="K -> E (in Ref. 5; BAG36881)"
FT /evidence="ECO:0000305"
FT CONFLICT 278
FT /note="R -> T (in Ref. 4; AAC50951)"
FT /evidence="ECO:0000305"
FT CONFLICT 374
FT /note="K -> R (in Ref. 4; AAC50951)"
FT /evidence="ECO:0000305"
FT CONFLICT 383
FT /note="I -> V (in Ref. 9; AAH32322)"
FT /evidence="ECO:0000305"
FT TURN 75..77
FT /evidence="ECO:0007829|PDB:6UEZ"
FT HELIX 80..85
FT /evidence="ECO:0007829|PDB:6UEZ"
FT HELIX 87..98
FT /evidence="ECO:0007829|PDB:6UEZ"
FT STRAND 100..106
FT /evidence="ECO:0007829|PDB:6UEZ"
FT STRAND 109..114
FT /evidence="ECO:0007829|PDB:6UEZ"
FT HELIX 117..125
FT /evidence="ECO:0007829|PDB:6UEZ"
FT TURN 128..130
FT /evidence="ECO:0007829|PDB:6UEZ"
FT STRAND 131..133
FT /evidence="ECO:0007829|PDB:6UEZ"
FT HELIX 134..145
FT /evidence="ECO:0007829|PDB:6UEZ"
FT HELIX 150..152
FT /evidence="ECO:0007829|PDB:6UEZ"
FT HELIX 155..165
FT /evidence="ECO:0007829|PDB:6UEZ"
FT TURN 166..168
FT /evidence="ECO:0007829|PDB:6UEZ"
FT HELIX 171..189
FT /evidence="ECO:0007829|PDB:6UEZ"
FT HELIX 190..192
FT /evidence="ECO:0007829|PDB:6UEZ"
FT STRAND 194..199
FT /evidence="ECO:0007829|PDB:6UEZ"
FT HELIX 200..216
FT /evidence="ECO:0007829|PDB:6UEZ"
FT HELIX 219..223
FT /evidence="ECO:0007829|PDB:6UEZ"
FT HELIX 229..237
FT /evidence="ECO:0007829|PDB:6UEZ"
FT HELIX 242..246
FT /evidence="ECO:0007829|PDB:6UEZ"
FT STRAND 252..254
FT /evidence="ECO:0007829|PDB:6UEZ"
FT HELIX 255..277
FT /evidence="ECO:0007829|PDB:6UEZ"
FT HELIX 288..292
FT /evidence="ECO:0007829|PDB:6UEZ"
FT STRAND 297..299
FT /evidence="ECO:0007829|PDB:6Q2T"
FT HELIX 304..335
FT /evidence="ECO:0007829|PDB:6UEZ"
FT HELIX 337..351
FT /evidence="ECO:0007829|PDB:6UEZ"
FT HELIX 360..363
FT /evidence="ECO:0007829|PDB:6UEZ"
FT HELIX 367..379
FT /evidence="ECO:0007829|PDB:6UEZ"
FT STRAND 386..392
FT /evidence="ECO:0007829|PDB:6UEZ"
FT STRAND 394..396
FT /evidence="ECO:0007829|PDB:6UEZ"
FT STRAND 399..401
FT /evidence="ECO:0007829|PDB:6UEZ"
FT STRAND 406..409
FT /evidence="ECO:0007829|PDB:6UEZ"
FT HELIX 411..414
FT /evidence="ECO:0007829|PDB:6UEZ"
FT TURN 418..420
FT /evidence="ECO:0007829|PDB:6UEZ"
FT TURN 422..425
FT /evidence="ECO:0007829|PDB:6UEZ"
FT HELIX 429..433
FT /evidence="ECO:0007829|PDB:6UEZ"
FT HELIX 437..440
FT /evidence="ECO:0007829|PDB:6UEZ"
FT STRAND 441..445
FT /evidence="ECO:0007829|PDB:6UEZ"
FT HELIX 451..453
FT /evidence="ECO:0007829|PDB:6UEZ"
FT HELIX 458..475
FT /evidence="ECO:0007829|PDB:6UEZ"
FT STRAND 476..479
FT /evidence="ECO:0007829|PDB:6UEZ"
FT STRAND 481..483
FT /evidence="ECO:0007829|PDB:3JUV"
FT STRAND 491..494
FT /evidence="ECO:0007829|PDB:6UEZ"
FT STRAND 496..499
FT /evidence="ECO:0007829|PDB:6UEZ"
FT STRAND 501..506
FT /evidence="ECO:0007829|PDB:6UEZ"
SQ SEQUENCE 509 AA; 57278 MW; F9145DDB65F94091 CRC64;
MAAAAGMLLL GLLQAGGSVL GQAMEKVTGG NLLSMLLIAC AFTLSLVYLI RLAAGHLVQL
PAGVKSPPYI FSPIPFLGHA IAFGKSPIEF LENAYEKYGP VFSFTMVGKT FTYLLGSDAA
ALLFNSKNED LNAEDVYSRL TTPVFGKGVA YDVPNPVFLE QKKMLKSGLN IAHFKQHVSI
IEKETKEYFE SWGESGEKNV FEALSELIIL TASHCLHGKE IRSQLNEKVA QLYADLDGGF
SHAAWLLPGW LPLPSFRRRD RAHREIKDIF YKAIQKRRQS QEKIDDILQT LLDATYKDGR
PLTDDEVAGM LIGLLLAGQH TSSTTSAWMG FFLARDKTLQ KKCYLEQKTV CGENLPPLTY
DQLKDLNLLD RCIKETLRLR PPIMIMMRMA RTPQTVAGYT IPPGHQVCVS PTVNQRLKDS
WVERLDFNPD RYLQDNPASG EKFAYVPFGA GRHRCIGENF AYVQIKTIWS TMLRLYEFDL
IDGYFPTVNY TTMIHTPENP VIRYKRRSK
