Q16850 (CP51A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	503 AA.
Sequence status	Complete.
Protein existence	Evidence 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.
Catalytic activity	Obtusifoliol + 3 O2 + 3 NADPH = 4-alpha-methyl-5-alpha-ergosta-8,14,24(28)-trien-3-beta-ol + formate + 3 NADP+ + 4 H2O.
Cofactor	Heme group By similarity.
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 process	Cholesterol biosynthesis Lipid synthesis Steroid biosynthesis Sterol biosynthesis
Cellular component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Heme Iron Metal-binding NADP
Molecular function	Monooxygenase Oxidoreductase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	cholesterol biosynthetic process Traceable author statement. Source: Reactome xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW microsome Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred from electronic annotation. Source: InterPro sterol 14-demethylase activity Inferred from electronic annotation. Source: EC
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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 503

503

Lanosterol 14-alpha demethylase

PRO_0000051998

Regions

Transmembrane

24 – 44

21

Helical; Potential

Sites

Metal binding

449

1

Iron (heme axial ligand) By similarity

Natural variations

Alternative sequence

1 – 99

99

Missing in isoform 2.

VSP_037413

Natural variant

13

1

V → A.
Corresponds to variant rs2229188 [ dbSNP | Ensembl ].

VAR_023470

Experimental info

Sequence conflict

270

1

K → E in BAG36881. Ref.5

Sequence conflict

272

1

R → T in AAC50951. Ref.4

Sequence conflict

368

1

K → R in AAC50951. Ref.4

Sequence conflict

377

1

I → V in AAH32322. Ref.9

Secondary structure

1

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503

Helix Strand Turn

Details...

Beta strand

67 – 69

3

Turn

74 – 76

3

Helix

81 – 91

11

Beta strand

95 – 99

5

Beta strand

104 – 108

5

Turn

112 – 114

3

Helix

115 – 119

5

Turn

122 – 124

3

Beta strand

125 – 127

3

Helix

128 – 138

11

Helix

144 – 146

3

Helix

149 – 160

12

Helix

165 – 182

18

Helix

183 – 185

3

Helix

194 – 210

17

Helix

214 – 217

4

Helix

221 – 230

10

Helix

236 – 240

5

Helix

248 – 271

24

Helix

281 – 286

6

Helix

298 – 301

4

Helix

314 – 322

9

Helix

326 – 329

4

Helix

331 – 344

14

Helix

354 – 358

5

Helix

361 – 373

13

Beta strand

380 – 384

5

Beta strand

400 – 403

4

Helix

405 – 408

4

Turn

412 – 414

3

Turn

416 – 419

4

Helix

423 – 427

5

Beta strand

437 – 439

3

Helix

453 – 469

17

Beta strand

470 – 473

4

Beta strand

485 – 488

4

Beta strand

491 – 493

3

Beta strand

495 – 500

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified December 15, 1998. Version 3. Checksum: 4FCEC147FB4DED86	FASTA	503	56,806
	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
	Isoform 2 [UniParc]. Checksum: 2D5198C9B55ED478	FASTA	404	46,312
	10 20 30 40 50 60 MVGKTFTYLL GSDAAALLFN SKNEDLNAED VYSRLTTPVF GKGVAYDVPN PVFLEQKKML 70 80 90 100 110 120 KSGLNIAHFK QHVSIIEKET KEYFESWGES GEKNVFEALS ELIILTASHC LHGKEIRSQL 130 140 150 160 170 180 NEKVAQLYAD LDGGFSHAAW LLPGWLPLPS FRRRDRAHRE IKDIFYKAIQ KRRQSQEKID 190 200 210 220 230 240 DILQTLLDAT YKDGRPLTDD EVAGMLIGLL LAGQHTSSTT SAWMGFFLAR DKTLQKKCYL 250 260 270 280 290 300 EQKTVCGENL PPLTYDQLKD LNLLDRCIKE TLRLRPPIMI MMRMARTPQT VAGYTIPPGH 310 320 330 340 350 360 QVCVSPTVNQ RLKDSWVERL DFNPDRYLQD NPASGEKFAY VPFGAGRHRC IGENFAYVQI 370 380 390 400 KTIWSTMLRL YEFDLIDGYF PTVNYTTMIH TPENPVIRYK RRSK

References

	« Hide 'large scale' referencesShow '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: 8619637] [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: 8797093] [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: 8809088] [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: 8975714] [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. , 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: 14702039] [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. , 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: 12853948] [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. , 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: 12690205] [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. , 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: 15489334] [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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	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 , 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.

IPI

IPI00295772.
IPI00926839.

PIR

JC4759.
S68855.

RefSeq

NP_000777.1. NM_000786.3.
NP_001139624.1. NM_001146152.1.

UniGene

Hs.417077.

3D structure databases

PDBe
RCSB PDB
PDBj

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	[»]

ProteinModelPortal

Q16850.

SMR

Q16850. Positions 58-502.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q16850. 2 interactions.

STRING

Q16850.

Polymorphism databases

DMDM

3915660.

Proteomic databases

PRIDE

Q16850.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000003100; ENSP00000003100; ENSG00000001630.

GeneID

1595.

KEGG

hsa:1595.

UCSC

uc003ulm.2. human.

Organism-specific databases

CTD

1595.

GeneCards

GC07M091741.

H-InvDB

HIX0130618.
HIX0201141.

HGNC

HGNC:2649. CYP51A1.

MIM

601637. gene.

neXtProt

NX_Q16850.

PharmGKB

PA27123.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG08769.

GeneTree

ENSGT00440000033325.

HOVERGEN

HBG051102.

InParanoid

Q16850.

OrthoDB

EOG4M0F1P.

PhylomeDB

Q16850.

Enzyme and pathway databases

BioCyc

MetaCyc:ENSG00000001630-MONOMER.

Reactome

REACT_111217. Metabolism.
REACT_22258. Metabolism of lipids and lipoproteins.

Gene expression databases

ArrayExpress

Q16850.

Bgee

Q16850.

CleanEx

HS_CYP51A1.

Genevestigator

Q16850.

GermOnline

ENSG00000001630. Homo sapiens.

Family and domain databases

InterPro

IPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002403. Cyt_P450_E_grp-IV.
[Graphical view]

Gene3D

G3DSA:1.10.630.10. Cyt_P450. 1 hit.

KO

K05917.

Pfam

PF00067. p450. 1 hit.
[Graphical view]

PRINTS

PR00465. EP450IV.
PR00385. P450.

SUPFAM

SSF48264. Cytochrome_P450. 1 hit.

PROSITE

PS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

DrugBank

DB00196. Fluconazole.
DB01167. Itraconazole.
DB01026. Ketoconazole.
DB01110. Miconazole.
DB00251. Terconazole.

NextBio

6556.

SOURCE

Search...

Entry information

Entry name

CP51A_HUMAN

Accession

Primary (citable) accession number: Q16850
Secondary accession number(s): A4D1F8 , 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:	January 25, 2012
This is version 114 of the entry and version 3 of the sequence. [Complete history]

Entry status

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.