UniProtKB - Q16850 (CP51A_HUMAN)
Protein
Lanosterol 14-alpha demethylase
Gene
CYP51A1
Organism
Homo sapiens (Human)
Status
Functioni
A cytochrome P450 monooxygenase involved in sterol biosynthesis. Catalyzes 14-alpha demethylation of lanosterol and 24,25-dihydrolanosterol likely through sequential oxidative conversion of 14-alpha methyl group to hydroxymethyl, then to carboxylaldehyde, followed by the formation of the delta 14,15 double bond in the sterol core and concomitant release of formic acid (PubMed:20149798, PubMed:8619637). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (CPR; NADPH-ferrihemoprotein reductase) (PubMed:20149798, PubMed:8619637).2 Publications
Catalytic activityi
- a 14α-methyl steroid + 3 O2 + 3 reduced [NADPH—hemoprotein reductase] = a Δ14 steroid + formate + 4 H+ + 4 H2O + 3 oxidized [NADPH—hemoprotein reductase]2 PublicationsEC:1.14.14.1542 PublicationsThis reaction proceeds in the forward2 Publications direction.
- lanosterol + 3 O2 + 3 reduced [NADPH—hemoprotein reductase] = 4,4-dimethyl-5α-cholesta-8,14,24-trien-3β-ol + formate + 4 H+ + 4 H2O + 3 oxidized [NADPH—hemoprotein reductase]1 PublicationEC:1.14.14.1541 PublicationThis reaction proceeds in the forward1 Publication direction.
- 24,25-dihydrolanosterol + 3 O2 + 3 reduced [NADPH—hemoprotein reductase] = 4,4-dimethyl-8,14-cholestadien-3β-ol + formate + 4 H+ + 4 H2O + 3 oxidized [NADPH—hemoprotein reductase]1 PublicationThis reaction proceeds in the forward1 Publication direction.
Cofactori
heme1 Publication
Activity regulationi
Inhibited by azalanstat. Inhibited by azole antifungal agents ketoconazole, itraconazole and fluconazole.By similarity
: zymosterol biosynthesis Pathwayi
This protein is involved in step 1 of the subpathway that synthesizes zymosterol from lanosterol.1 PublicationProteins known to be involved in the 6 steps of the subpathway in this organism are:
- Lanosterol 14-alpha demethylase (CYP51A1)
- no protein annotated in this organism
- Methylsterol monooxygenase 1 (MSMO1)
- Sterol-4-alpha-carboxylate 3-dehydrogenase, decarboxylating (NSDHL)
- 3-keto-steroid reductase (hCG_2024989), 3-keto-steroid reductase/17-beta-hydroxysteroid dehydrogenase 7 (HSD17B7)
- no protein annotated in this organism
View all proteins of this organism that are known to be involved in the subpathway that synthesizes zymosterol from lanosterol, the pathway zymosterol biosynthesis and in Steroid biosynthesis.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 449 | Iron (heme axial ligand)1 Publication | 1 |
GO - Molecular functioni
- heme binding Source: UniProtKB
- iron ion binding Source: InterPro
- monooxygenase activity Source: GO_Central
- oxidoreductase activity Source: GO_Central
- sterol 14-demethylase activity Source: UniProtKB
GO - Biological processi
- cholesterol biosynthetic process Source: Reactome
- negative regulation of amyloid-beta clearance Source: ARUK-UCL
- negative regulation of protein catabolic process Source: ARUK-UCL
- negative regulation of protein secretion Source: ARUK-UCL
- oxidation-reduction process Source: GO_Central
- regulation of cholesterol biosynthetic process Source: Reactome
- steroid biosynthetic process Source: UniProtKB
- sterol metabolic process Source: GO_Central
Keywordsi
Molecular function | Monooxygenase, Oxidoreductase |
Biological process | Cholesterol biosynthesis, Cholesterol metabolism, Lipid biosynthesis, Lipid metabolism, Steroid biosynthesis, Steroid metabolism, Sterol biosynthesis, Sterol metabolism |
Ligand | Heme, Iron, Metal-binding |
Enzyme and pathway databases
BioCyci | MetaCyc:HS00076-MONOMER |
BRENDAi | 1.14.13.70, 2681 |
PathwayCommonsi | Q16850 |
Reactomei | R-HSA-191273, Cholesterol biosynthesis R-HSA-211976, Endogenous sterols R-HSA-2426168, Activation of gene expression by SREBF (SREBP) R-HSA-9619665, EGR2 and SOX10-mediated initiation of Schwann cell myelination |
UniPathwayi | UPA00770;UER00754 |
Chemistry databases
SwissLipidsi | SLP:000001162 |
Names & Taxonomyi
Protein namesi | Recommended name: Lanosterol 14-alpha demethylase (EC:1.14.14.1542 Publications)Short name: LDM Alternative name(s): CYPLI Cytochrome P450 51A1 Cytochrome P450-14DM Short name: Cytochrome P45014DM Cytochrome P450LI Sterol 14-alpha demethylase |
Gene namesi | Name:CYP51A1 Synonyms:CYP51 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:2649, CYP51A1 |
MIMi | 601637, gene |
neXtProti | NX_Q16850 |
VEuPathDBi | HostDB:ENSG00000001630.15 |
Subcellular locationi
Endoplasmic reticulum
- Endoplasmic reticulum membrane By similarity; Single-pass membrane protein Sequence analysis
- Microsome membrane By similarity; Single-pass membrane protein Sequence analysis
Endoplasmic reticulum
- endoplasmic reticulum Source: HPA
- endoplasmic reticulum membrane Source: Reactome
Other locations
- integral component of membrane Source: UniProtKB-KW
- membrane Source: UniProtKB
Topology
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Transmembranei | 24 – 44 | HelicalSequence analysisAdd BLAST | 21 |
Keywords - Cellular componenti
Endoplasmic reticulum, Membrane, MicrosomePathology & Biotechi
Organism-specific databases
DisGeNETi | 1595 |
MalaCardsi | CYP51A1 |
OpenTargetsi | ENSG00000001630 |
Orphaneti | 521432, Congenital cataract-severe neonatal hepatopathy-global developmental delay syndrome |
PharmGKBi | PA27123 |
Miscellaneous databases
Pharosi | Q16850, Tchem |
Chemistry databases
ChEMBLi | CHEMBL3849 |
DrugBanki | DB07705, (S)-econazole DB01167, Itraconazole DB05667, Levoketoconazole DB01110, Miconazole DB01007, Tioconazole |
DrugCentrali | Q16850 |
GuidetoPHARMACOLOGYi | 1374 |
Genetic variation databases
BioMutai | CYP51A1 |
DMDMi | 3915660 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000051998 | 1 – 503 | Lanosterol 14-alpha demethylaseAdd BLAST | 503 |
Proteomic databases
EPDi | Q16850 |
jPOSTi | Q16850 |
MassIVEi | Q16850 |
MaxQBi | Q16850 |
PaxDbi | Q16850 |
PeptideAtlasi | Q16850 |
PRIDEi | Q16850 |
ProteomicsDBi | 61101 [Q16850-1] 61102 [Q16850-2] |
PTM databases
iPTMneti | Q16850 |
PhosphoSitePlusi | Q16850 |
SwissPalmi | Q16850 |
Expressioni
Tissue specificityi
Ubiquitously expressed with highest levels in testis, ovary, adrenal, prostate, liver, kidney and lung.1 Publication
Gene expression databases
Bgeei | ENSG00000001630, Expressed in adrenal tissue and 122 other tissues |
ExpressionAtlasi | Q16850, baseline and differential |
Genevisiblei | Q16850, HS |
Organism-specific databases
HPAi | ENSG00000001630, Tissue enhanced (liver) |
Interactioni
Protein-protein interaction databases
BioGRIDi | 107967, 71 interactors |
IntActi | Q16850, 16 interactors |
STRINGi | 9606.ENSP00000003100 |
Chemistry databases
BindingDBi | Q16850 |
Miscellaneous databases
RNActi | Q16850, protein |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q16850 |
ModBasei | Search... |
PDBe-KBi | Search... |
Miscellaneous databases
EvolutionaryTracei | Q16850 |
Family & Domainsi
Sequence similaritiesi
Belongs to the cytochrome P450 family.Curated
Keywords - Domaini
Transmembrane, Transmembrane helixPhylogenomic databases
eggNOGi | KOG0684, Eukaryota |
GeneTreei | ENSGT00930000151026 |
HOGENOMi | CLU_001570_15_0_1 |
InParanoidi | Q16850 |
OrthoDBi | 559299at2759 |
PhylomeDBi | Q16850 |
TreeFami | TF105091 |
Family and domain databases
Gene3Di | 1.10.630.10, 1 hit |
InterProi | View protein in InterPro IPR001128, Cyt_P450 IPR017972, Cyt_P450_CS IPR002403, Cyt_P450_E_grp-IV IPR036396, Cyt_P450_sf |
Pfami | View protein in Pfam PF00067, p450, 1 hit |
PRINTSi | PR00465, EP450IV PR00385, P450 |
SUPFAMi | SSF48264, SSF48264, 1 hit |
PROSITEi | View protein in PROSITE PS00086, CYTOCHROME_P450, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 2 potential isoforms that are computationally mapped.Show allAlign All
Isoform 1 (identifier: Q16850-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MLLLGLLQAG GSVLGQAMEK VTGGNLLSML LIACAFTLSL VYLIRLAAGH
60 70 80 90 100
LVQLPAGVKS PPYIFSPIPF LGHAIAFGKS PIEFLENAYE KYGPVFSFTM
110 120 130 140 150
VGKTFTYLLG SDAAALLFNS KNEDLNAEDV YSRLTTPVFG KGVAYDVPNP
160 170 180 190 200
VFLEQKKMLK SGLNIAHFKQ HVSIIEKETK EYFESWGESG EKNVFEALSE
210 220 230 240 250
LIILTASHCL HGKEIRSQLN EKVAQLYADL DGGFSHAAWL LPGWLPLPSF
260 270 280 290 300
RRRDRAHREI KDIFYKAIQK RRQSQEKIDD ILQTLLDATY KDGRPLTDDE
310 320 330 340 350
VAGMLIGLLL AGQHTSSTTS AWMGFFLARD KTLQKKCYLE QKTVCGENLP
360 370 380 390 400
PLTYDQLKDL NLLDRCIKET LRLRPPIMIM MRMARTPQTV AGYTIPPGHQ
410 420 430 440 450
VCVSPTVNQR LKDSWVERLD FNPDRYLQDN PASGEKFAYV PFGAGRHRCI
460 470 480 490 500
GENFAYVQIK TIWSTMLRLY EFDLIDGYFP TVNYTTMIHT PENPVIRYKR
RSK
Computationally mapped potential isoform sequencesi
There are 2 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketA0A0C4DFL7 | A0A0C4DFL7_HUMAN | Lanosterol 14-alpha demethylase | CYP51A1 | 509 | Annotation score: | ||
H7C0D0 | H7C0D0_HUMAN | Lanosterol 14-alpha demethylase | CYP51A1 | 222 | Annotation score: |
Sequence cautioni
The sequence AAB39951 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated
The sequence AAB46356 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated
The sequence AAH32322 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated
The sequence BAA09512 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated
The sequence BAG36881 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated
The sequence EAL24154 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated
The sequence EAW76858 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 270 | K → E in BAG36881 (PubMed:14702039).Curated | 1 | |
Sequence conflicti | 272 | R → T in AAC50951 (PubMed:8975714).Curated | 1 | |
Sequence conflicti | 368 | K → R in AAC50951 (PubMed:8975714).Curated | 1 | |
Sequence conflicti | 377 | I → V in AAH32322 (PubMed:15489334).Curated | 1 |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_023470 | 13 | V → A. Corresponds to variant dbSNP:rs2229188Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_037413 | 1 – 99 | Missing in isoform 2. 1 PublicationAdd BLAST | 99 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U23942 mRNA Translation: AAB39951.1 Different initiation. D55653 mRNA Translation: BAA09512.1 Different initiation. U51692 , 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. |
CCDSi | CCDS55123.1 [Q16850-2] |
PIRi | JC4759 S68855 |
RefSeqi | NP_000777.1, NM_000786.3 NP_001139624.1, NM_001146152.1 [Q16850-2] |
Genome annotation databases
Ensembli | ENST00000450723; ENSP00000406757; ENSG00000001630 [Q16850-2] |
GeneIDi | 1595 |
KEGGi | hsa:1595 |
UCSCi | uc003ulm.5, human [Q16850-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U23942 mRNA Translation: AAB39951.1 Different initiation. D55653 mRNA Translation: BAA09512.1 Different initiation. U51692 , 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. |
CCDSi | CCDS55123.1 [Q16850-2] |
PIRi | JC4759 S68855 |
RefSeqi | NP_000777.1, NM_000786.3 NP_001139624.1, NM_001146152.1 [Q16850-2] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3JUS | X-ray | 2.90 | A/B | 54-502 | [»] | |
3JUV | X-ray | 3.12 | A | 54-502 | [»] | |
3LD6 | X-ray | 2.80 | A/B | 54-502 | [»] | |
4UHI | X-ray | 2.04 | A/B/C/D | 61-503 | [»] | |
4UHL | X-ray | 2.50 | A/B/C/D/E/F/G/H | 61-503 | [»] | |
6Q2T | X-ray | 2.80 | A/B | 61-503 | [»] | |
6UEZ | X-ray | 1.98 | A/B | 61-503 | [»] | |
SMRi | Q16850 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 107967, 71 interactors |
IntActi | Q16850, 16 interactors |
STRINGi | 9606.ENSP00000003100 |
Chemistry databases
BindingDBi | Q16850 |
ChEMBLi | CHEMBL3849 |
DrugBanki | DB07705, (S)-econazole DB01167, Itraconazole DB05667, Levoketoconazole DB01110, Miconazole DB01007, Tioconazole |
DrugCentrali | Q16850 |
GuidetoPHARMACOLOGYi | 1374 |
SwissLipidsi | SLP:000001162 |
PTM databases
iPTMneti | Q16850 |
PhosphoSitePlusi | Q16850 |
SwissPalmi | Q16850 |
Genetic variation databases
BioMutai | CYP51A1 |
DMDMi | 3915660 |
Proteomic databases
EPDi | Q16850 |
jPOSTi | Q16850 |
MassIVEi | Q16850 |
MaxQBi | Q16850 |
PaxDbi | Q16850 |
PeptideAtlasi | Q16850 |
PRIDEi | Q16850 |
ProteomicsDBi | 61101 [Q16850-1] 61102 [Q16850-2] |
Protocols and materials databases
Antibodypediai | 34871, 260 antibodies |
DNASUi | 1595 |
Genome annotation databases
Ensembli | ENST00000450723; ENSP00000406757; ENSG00000001630 [Q16850-2] |
GeneIDi | 1595 |
KEGGi | hsa:1595 |
UCSCi | uc003ulm.5, human [Q16850-1] |
Organism-specific databases
CTDi | 1595 |
DisGeNETi | 1595 |
GeneCardsi | CYP51A1 |
HGNCi | HGNC:2649, CYP51A1 |
HPAi | ENSG00000001630, Tissue enhanced (liver) |
MalaCardsi | CYP51A1 |
MIMi | 601637, gene |
neXtProti | NX_Q16850 |
OpenTargetsi | ENSG00000001630 |
Orphaneti | 521432, Congenital cataract-severe neonatal hepatopathy-global developmental delay syndrome |
PharmGKBi | PA27123 |
VEuPathDBi | HostDB:ENSG00000001630.15 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG0684, Eukaryota |
GeneTreei | ENSGT00930000151026 |
HOGENOMi | CLU_001570_15_0_1 |
InParanoidi | Q16850 |
OrthoDBi | 559299at2759 |
PhylomeDBi | Q16850 |
TreeFami | TF105091 |
Enzyme and pathway databases
UniPathwayi | UPA00770;UER00754 |
BioCyci | MetaCyc:HS00076-MONOMER |
BRENDAi | 1.14.13.70, 2681 |
PathwayCommonsi | Q16850 |
Reactomei | R-HSA-191273, Cholesterol biosynthesis R-HSA-211976, Endogenous sterols R-HSA-2426168, Activation of gene expression by SREBF (SREBP) R-HSA-9619665, EGR2 and SOX10-mediated initiation of Schwann cell myelination |
Miscellaneous databases
BioGRID-ORCSi | 1595, 14 hits in 874 CRISPR screens |
ChiTaRSi | CYP51A1, human |
EvolutionaryTracei | Q16850 |
GenomeRNAii | 1595 |
Pharosi | Q16850, Tchem |
PROi | PR:Q16850 |
RNActi | Q16850, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000001630, Expressed in adrenal tissue and 122 other tissues |
ExpressionAtlasi | Q16850, baseline and differential |
Genevisiblei | Q16850, HS |
Family and domain databases
Gene3Di | 1.10.630.10, 1 hit |
InterProi | View protein in InterPro IPR001128, Cyt_P450 IPR017972, Cyt_P450_CS IPR002403, Cyt_P450_E_grp-IV IPR036396, Cyt_P450_sf |
Pfami | View protein in Pfam PF00067, p450, 1 hit |
PRINTSi | PR00465, EP450IV PR00385, P450 |
SUPFAMi | SSF48264, SSF48264, 1 hit |
PROSITEi | View protein in PROSITE PS00086, CYTOCHROME_P450, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | CP51A_HUMAN | |
Accessioni | Q16850Primary (citable) accession number: Q16850 Secondary accession number(s): A4D1F8 Q99868 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | December 15, 1998 | |
Last modified: | February 10, 2021 | |
This is version 191 of the entry and version 3 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 7
Human chromosome 7: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PATHWAY comments
Index of metabolic and biosynthesis pathways - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families