Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q16850 (CP51A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Lanosterol 14-alpha demethylase

Short name=LDM
EC=1.14.13.70
Alternative name(s):
CYPLI
Cytochrome P450 51A1
Cytochrome P450-14DM
Short name=Cytochrome P45014DM
Cytochrome P450LI
Sterol 14-alpha demethylase
Gene names
Name:CYP51A1
Synonyms:CYP51
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length503 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes C14-demethylation of lanosterol; it transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol. Ref.11

Catalytic activity

A 14-alpha-methylsteroid + 3 O2 + 3 NADPH = a Delta(14)-steroid + formate + 3 NADP+ + 4 H2O. Ref.11

Cofactor

Heme group. Ref.11

Pathway

Steroid biosynthesis; zymosterol biosynthesis; zymosterol from lanosterol: step 1/6.

Subcellular location

Endoplasmic reticulum membrane Potential. Microsome membrane Potential.

Tissue specificity

Ubiquitously expressed with highest levels in testis, ovary, adrenal, prostate, liver, kidney and lung. Ref.1

Sequence similarities

Belongs to the cytochrome P450 family.

Sequence caution

The sequence AAB39951.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAB46356.1 differs from that shown. Reason: Erroneous initiation.

The sequence AAH32322.1 differs from that shown. Reason: Erroneous initiation.

The sequence BAA09512.1 differs from that shown. Reason: Erroneous initiation.

The sequence BAG36881.1 differs from that shown. Reason: Erroneous initiation.

The sequence EAL24154.1 differs from that shown. Reason: Erroneous initiation.

The sequence EAW76858.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processCholesterol biosynthesis
Cholesterol metabolism
Lipid biosynthesis
Lipid metabolism
Steroid biosynthesis
Steroid metabolism
Sterol biosynthesis
Sterol metabolism
   Cellular componentEndoplasmic reticulum
Membrane
Microsome
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainTransmembrane
Transmembrane helix
   LigandHeme
Iron
Metal-binding
NADP
   Molecular functionMonooxygenase
Oxidoreductase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcholesterol biosynthetic process

Traceable author statement. Source: Reactome

cholesterol biosynthetic process via 24,25-dihydrolanosterol

Inferred from electronic annotation. Source: Ensembl

demethylation

Inferred from direct assay Ref.11. Source: GOC

small molecule metabolic process

Traceable author statement. Source: Reactome

steroid biosynthetic process

Inferred from direct assay Ref.11. Source: UniProtKB

sterol metabolic process

Traceable author statement. Source: Reactome

xenobiotic metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentendoplasmic reticulum

Inferred from direct assay. Source: HPA

endoplasmic reticulum membrane

Traceable author statement. Source: Reactome

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionheme binding

Inferred from direct assay Ref.11. Source: UniProtKB

iron ion binding

Inferred from electronic annotation. Source: InterPro

sterol 14-demethylase activity

Inferred from direct assay Ref.11. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q16850-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q16850-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-99: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 503503Lanosterol 14-alpha demethylase
PRO_0000051998

Regions

Transmembrane24 – 4421Helical; Potential

Sites

Metal binding4491Iron (heme axial ligand)

Natural variations

Alternative sequence1 – 9999Missing in isoform 2.
VSP_037413
Natural variant131V → A.
Corresponds to variant rs2229188 [ dbSNP | Ensembl ].
VAR_023470

Experimental info

Sequence conflict2701K → E in BAG36881. Ref.5
Sequence conflict2721R → T in AAC50951. Ref.4
Sequence conflict3681K → R in AAC50951. Ref.4
Sequence conflict3771I → V in AAH32322. Ref.9

Secondary structure

............................................................................. 503
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 15, 1998. Version 3.
Checksum: 4FCEC147FB4DED86

FASTA50356,806
        10         20         30         40         50         60 
MLLLGLLQAG GSVLGQAMEK VTGGNLLSML LIACAFTLSL VYLIRLAAGH LVQLPAGVKS 

        70         80         90        100        110        120 
PPYIFSPIPF LGHAIAFGKS PIEFLENAYE KYGPVFSFTM VGKTFTYLLG SDAAALLFNS 

       130        140        150        160        170        180 
KNEDLNAEDV YSRLTTPVFG KGVAYDVPNP VFLEQKKMLK SGLNIAHFKQ HVSIIEKETK 

       190        200        210        220        230        240 
EYFESWGESG EKNVFEALSE LIILTASHCL HGKEIRSQLN EKVAQLYADL DGGFSHAAWL 

       250        260        270        280        290        300 
LPGWLPLPSF RRRDRAHREI KDIFYKAIQK RRQSQEKIDD ILQTLLDATY KDGRPLTDDE 

       310        320        330        340        350        360 
VAGMLIGLLL AGQHTSSTTS AWMGFFLARD KTLQKKCYLE QKTVCGENLP PLTYDQLKDL 

       370        380        390        400        410        420 
NLLDRCIKET LRLRPPIMIM MRMARTPQTV AGYTIPPGHQ VCVSPTVNQR LKDSWVERLD 

       430        440        450        460        470        480 
FNPDRYLQDN PASGEKFAYV PFGAGRHRCI GENFAYVQIK TIWSTMLRLY EFDLIDGYFP 

       490        500 
TVNYTTMIHT PENPVIRYKR RSK 

« Hide

Isoform 2 [UniParc].

Checksum: 2D5198C9B55ED478
Show »

FASTA40446,312

References

« Hide 'large scale' references
[1]"The ubiquitously expressed human CYP51 encodes lanosterol 14 alpha-demethylase, a cytochrome P450 whose expression is regulated by oxysterols."
Stroemstedt M., Rozman D., Waterman M.R.
Arch. Biochem. Biophys. 329:73-81(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
Tissue: Liver.
[2]"Sterol 14-demethylase P450 (P45014DM*) is one of the most ancient and conserved P450 species."
Aoyama Y., Noshiro M., Gotoh O., Imaoka S., Funae Y., Kurosawa N., Horiuchi T., Yoshida Y.
J. Biochem. 119:926-933(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Liver.
[3]"The three human cytochrome P450 lanosterol 14 alpha-demethylase (CYP51) genes reside on chromosomes 3, 7, and 13: structure of the two retrotransposed pseudogenes, association with a line-1 element, and evolution of the human CYP51 family."
Rozman D., Stroemstedt M., Waterman M.R.
Arch. Biochem. Biophys. 333:466-474(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Liver.
[4]"Structure and mapping of the human lanosterol 14alpha-demethylase gene (CYP51) encoding the cytochrome P450 involved in cholesterol biosynthesis; comparison of exon/intron organization with other mammalian and fungal CYP genes."
Rozman D., Stroemstedt M., Tsui L.-C., Scherer S.W., Waterman M.R.
Genomics 38:371-381(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
[6]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]"Human chromosome 7: DNA sequence and biology."
Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. expand/collapse author list , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Brain.
[10]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]"Structural basis of human CYP51 inhibition by antifungal azoles."
Strushkevich N., Usanov S.A., Park H.W.
J. Mol. Biol. 397:1067-1078(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 54-502 IN COMPLEXES WITH HEME; KETOCONAZOLE AND ECONAZOLE, CATALYTIC ACTIVITY, FUNCTION, COFACTOR.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U23942 mRNA. Translation: AAB39951.1. Different initiation.
D55653 mRNA. Translation: BAA09512.1. Different initiation.
U51692 expand/collapse EMBL AC list , U51684, U51685, U51686, U51687, U51688, U51689, U51690, U51691 Genomic DNA. Translation: AAC50951.1.
AK314205 mRNA. Translation: BAG36881.1. Different initiation.
AK295932 mRNA. Translation: BAG58717.1.
AC000120 Genomic DNA. Translation: AAB46356.1. Different initiation.
CH236949 Genomic DNA. Translation: EAL24154.1. Different initiation.
CH471091 Genomic DNA. Translation: EAW76858.1. Different initiation.
CH471091 Genomic DNA. Translation: EAW76859.1.
BC032322 mRNA. Translation: AAH32322.1. Different initiation.
PIRJC4759.
S68855.
RefSeqNP_000777.1. NM_000786.3.
NP_001139624.1. NM_001146152.1.
UniGeneHs.417077.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3JUSX-ray2.90A/B54-502[»]
3JUVX-ray3.12A54-502[»]
3LD6X-ray2.80A/B54-502[»]
ProteinModelPortalQ16850.
SMRQ16850. Positions 58-502.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107967. 3 interactions.
IntActQ16850. 3 interactions.

Chemistry

BindingDBQ16850.
ChEMBLCHEMBL3849.
DrugBankDB00196. Fluconazole.
DB01167. Itraconazole.
DB01026. Ketoconazole.
DB01110. Miconazole.
DB00251. Terconazole.

PTM databases

PhosphoSiteQ16850.

Polymorphism databases

DMDM3915660.

Proteomic databases

PaxDbQ16850.
PRIDEQ16850.

Protocols and materials databases

DNASU1595.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000003100; ENSP00000003100; ENSG00000001630.
ENST00000450723; ENSP00000406757; ENSG00000001630. [Q16850-2]
GeneID1595.
KEGGhsa:1595.
UCSCuc003ulm.4. human. [Q16850-1]

Organism-specific databases

CTD1595.
GeneCardsGC07M091741.
HGNCHGNC:2649. CYP51A1.
HPAHPA041325.
HPA043508.
MIM601637. gene.
neXtProtNX_Q16850.
PharmGKBPA27123.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2124.
HOVERGENHBG051102.
InParanoidQ16850.
KOK05917.
OrthoDBEOG7PZRX3.
PhylomeDBQ16850.
TreeFamTF105091.

Enzyme and pathway databases

BioCycMetaCyc:HS00076-MONOMER.
ReactomeREACT_111217. Metabolism.
UniPathwayUPA00770; UER00754.

Gene expression databases

ArrayExpressQ16850.
BgeeQ16850.
CleanExHS_CYP51A1.
GenevestigatorQ16850.

Family and domain databases

Gene3D1.10.630.10. 1 hit.
InterProIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002403. Cyt_P450_E_grp-IV.
[Graphical view]
PfamPF00067. p450. 1 hit.
[Graphical view]
PRINTSPR00465. EP450IV.
PR00385. P450.
SUPFAMSSF48264. SSF48264. 1 hit.
PROSITEPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ16850.
GenomeRNAi1595.
NextBio6556.
PROQ16850.
SOURCESearch...

Entry information

Entry nameCP51A_HUMAN
AccessionPrimary (citable) accession number: Q16850
Secondary accession number(s): A4D1F8 expand/collapse secondary AC list , B2RAI4, B4DJ55, O00770, O00772, Q16784, Q8N1A8, Q99868
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: December 15, 1998
Last modified: April 16, 2014
This is version 135 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM