Lanosterol 14-alpha demethylase

Details

Name
Lanosterol 14-alpha demethylase
Kind
protein
Synonyms
  • 1.14.14.154
  • CYP51
  • CYP51A1
  • CYPLI
  • Cytochrome P450 51A1
  • Cytochrome P450-14DM
  • Cytochrome P45014DM
  • Cytochrome P450LI
  • LDM
  • Sterol 14-alpha demethylase
Gene Name
CYP51A1
UniProtKB Entry
Q16850Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0058080|Lanosterol 14-alpha demethylase
MAAAAGMLLLGLLQAGGSVLGQAMEKVTGGNLLSMLLIACAFTLSLVYLIRLAAGHLVQL
PAGVKSPPYIFSPIPFLGHAIAFGKSPIEFLENAYEKYGPVFSFTMVGKTFTYLLGSDAA
ALLFNSKNEDLNAEDVYSRLTTPVFGKGVAYDVPNPVFLEQKKMLKSGLNIAHFKQHVSI
IEKETKEYFESWGESGEKNVFEALSELIILTASHCLHGKEIRSQLNEKVAQLYADLDGGF
SHAAWLLPGWLPLPSFRRRDRAHREIKDIFYKAIQKRRQSQEKIDDILQTLLDATYKDGR
PLTDDEVAGMLIGLLLAGQHTSSTTSAWMGFFLARDKTLQKKCYLEQKTVCGENLPPLTY
DQLKDLNLLDRCIKETLRLRPPIMIMMRMARTPQTVAGYTIPPGHQVCVSPTVNQRLKDS
WVERLDFNPDRYLQDNPASGEKFAYVPFGAGRHRCIGENFAYVQIKTIWSTMLRLYEFDL
IDGYFPTVNYTTMIHTPENPVIRYKRRSK
Number of residues
509
Molecular Weight
57277.81
Theoretical pI
8.72
GO Classification
Functions
oxidoreductase activity
Processes
negative regulation of amyloid-beta clearance / negative regulation of protein catabolic process / negative regulation of protein secretion
General Function
Sterol 14alpha-demethylase that plays a critical role in the cholesterol biosynthesis pathway, being cholesterol the major sterol component in mammalian membranes as well as a precursor for bile acid and steroid hormone synthesis (PubMed:20149798, PubMed:8619637, PubMed:9559662). Cytochrome P450 monooxygenase that catalyzes the three-step oxidative removal of the 14alpha-methyl group (C-32) of sterols such as lanosterol (lanosta-8,24-dien-3beta-ol) and 24,25-dihydrolanosterol (DHL) in the form of formate, and converts the sterols to 4,4-dimethyl-5alpha-cholesta-8,14,24-trien-3beta-ol and 4,4-dimethyl-8,14-cholestadien-3beta-ol, respectively, which are intermediates of cholesterol biosynthesis (PubMed:20149798, PubMed:8619637, PubMed:9559662). Can also demethylate substrates not intrinsic to mammals, such as eburicol (24-methylene-24,25-dihydrolanosterol), but at a lower rate than DHL (PubMed:9559662)
Specific Function
Heme binding
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
30-50
Cellular Location
Endoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0010617|Lanosterol 14-alpha demethylase (CYP51A1)
ATGGCGGCGGCGGCTGGGATGCTGCTGCTGGGCTTGCTGCAGGCGGGTGGGTCGGTGCTG
GGCCAGGCGATGGAGAAGGTGACAGGCGGCAACCTCTTGTCCATGCTGCTGATCGCCTGC
GCCTTCACCCTCAGCCTGGTCTACCTGATCCGTCTGGCCGCCGGCCACCTGGTCCAGCTG
CCCGCAGGGGTGAAAAGTCCTCCATACATTTTCTCCCCAATTCCATTCCTTGGGCATGCC
ATAGCATTTGGGAAAAGTCCAATTGAATTTCTAGAAAATGCATATGAGAAGTATGGACCT
GTATTTAGTTTTACCATGGTAGGCAAGACATTTACTTACCTTCTGGGGAGTGATGCTGCT
GCACTGCTTTTTAATAGTAAAAATGAAGACCTGAATGCAGAAGATGTCTACAGTCGCCTG
ACAACACCTGTGTTTGGGAAGGGAGTTGCATACGATGTGCCTAATCCAGTTTTCTTGGAG
CAGAAGAAAATGTTAAAAAGTGGCCTTAACATAGCCCACTTTAAACAGCATGTTTCTATA
ATTGAAAAAGAAACAAAGGAATACTTTGAGAGTTGGGGAGAAAGTGGAGAAAAAAATGTG
TTTGAAGCTCTTTCTGAGCTCATAATTTTAACAGCTAGCCATTGTTTGCATGGAAAGGAA
ATCAGAAGTCAACTCAATGAAAAGGTAGCACAGCTGTATGCAGATTTGGATGGAGGTTTC
AGCCATGCAGCCTGGCTCTTACCAGGTTGGCTGCCTTTGCCTAGTTTCAGACGCAGGGAC
AGAGCTCATCGGGAAATCAAGGATATTTTCTATAAGGCAATCCAGAAACGCAGACAGTCT
CAAGAAAAAATTGATGACATTCTCCAAACTTTACTAGATGCTACATACAAGGATGGGCGT
CCTTTGACTGATGATGAAGTAGCAGGGATGCTTATTGGATTACTCTTGGCAGGGCAGCAT
ACATCCTCAACTACTAGTGCTTGGATGGGCTTCTTTTTGGCCAGAGACAAAACACTTCAA
AAAAAATGTTATTTAGAACAGAAAACAGTCTGTGGAGAGAATCTGCCTCCTTTAACTTAT
GACCAGCTCAAGGATCTAAATTTACTTGATCGCTGTATAAAAGAAACATTAAGACTTAGA
CCTCCTATAATGATCATGATGAGAATGGCCAGAACTCCTCAGACTGTGGCAGGGTATACC
ATTCCTCCAGGACATCAGGTGTGTGTTTCTCCCACTGTCAATCAAAGACTTAAAGACTCA
TGGGTAGAACGCCTGGACTTTAATCCTGATCGCTACTTACAGGATAACCCAGCATCAGGG
GAAAAGTTTGCCTATGTGCCATTTGGAGCTGGGCGTCATCGTTGTATTGGGGAAAATTTT
GCCTATGTTCAAATTAAGACAATTTGGTCCACTATGCTTCGTTTATATGAATTTGATCTC
ATTGATGGATACTTTCCCACTGTGAATTATACAACTATGATTCACACCCCTGAAAACCCA
GTTATCCGTTACAAACGAAGATCAAAATGA
Chromosome Location
7
Locus
7q21.2
External Identifiers
ResourceLink
UniProtKB IDQ16850
UniProtKB Entry NameCP51A_HUMAN
GenBank Protein ID1698396
GenBank Gene IDU23942
GeneCard IDCYP51A1
GenAtlas IDCYP51A1
HGNC IDHGNC:2649
PDB ID(s)3JUS, 3JUV, 3LD6, 4UHI, 4UHL, 6Q2T, 6UEZ, 8SBI, 8SS0
KEGG IDhsa:1595
IUPHAR/Guide To Pharmacology ID1374
NCBI Gene ID1595
General References
  1. Stromstedt M, Rozman D, Waterman MR: The ubiquitously expressed human CYP51 encodes lanosterol 14 alpha-demethylase, a cytochrome P450 whose expression is regulated by oxysterols. Arch Biochem Biophys. 1996 May 1;329(1):73-81. [Article]
  2. Aoyama Y, Noshiro M, Gotoh O, Imaoka S, Funae Y, Kurosawa N, Horiuchi T, Yoshida Y: Sterol 14-demethylase P450 (P45014DM*) is one of the most ancient and conserved P450 species. J Biochem. 1996 May;119(5):926-33. [Article]
  3. Rozman D, Stromstedt M, Waterman MR: 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. Arch Biochem Biophys. 1996 Sep 15;333(2):466-74. [Article]
  4. Rozman D, Stromstedt M, Tsui LC, Scherer SW, Waterman MR: 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. Genomics. 1996 Dec 15;38(3):371-81. [Article]
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Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
TioconazoleapprovedunknowntargetinhibitorDetails
Levoketoconazoleapproved, investigationalnotargetinhibitorDetails
(S)-econazoleexperimentalunknowntargetDetails
Miconazoleapproved, investigational, vet_approvedunknownenzymeinhibitorDetails
QuilseconazoleinvestigationalyestargetinhibitorDetails