Q7Z1V1 (CP51_TRYCC) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Sterol 14-alpha demethylase
Short name=Tc14DM
EC=1.14.13.70

Alternative name(s):
Cytochrome P450 51
Lanosterol 14-alpha demethylase

Gene names

Name:	CYP51
ORF Names:	Tc00.1047053506297.260, Tc00.1047053510101.50

Organism

Trypanosoma cruzi (strain CL Brener) [Complete proteome]

Taxonomic identifier

353153 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Euglenozoa › Kinetoplastida › Trypanosomatidae › Trypanosoma › Schizotrypanum › Trypanosoma cruzi

Protein attributes

Sequence length	481 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes C14-demethylation of lanosterol which is critical for ergosterol biosynthesis. It transforms lanosterol into 4,4'-dimethyl cholesta-8,14,24-triene-3-beta-ol By similarity. Favors C4 dimethylated substrates, the substrate preference order is 24-methylenedihydrolanosterol > 24,25-dihydrolanosterol > lanosterol > obtusifoliol > norlanosterol. Ref.2 UniProtKB P0A512
Catalytic activity	A 14-alpha-methylsteroid + 3 O2 + 3 NADPH = a Delta(14)-steroid + formate + 3 NADP+ + 4 H2O. Ref.2
Cofactor	Heme group By similarity. UniProtKB P0A512
Pathway	Steroid biosynthesis; zymosterol biosynthesis; zymosterol from lanosterol: step 1/6. UniProtKB P0A512
Subcellular location	Membrane; Single-pass membrane protein Potential.
Developmental stage	Expressed in both the insect and mammalian life-cycle stages. Ref.1
Sequence similarities	Belongs to the cytochrome P450 family.

Ontologies

Keywords
Biological process	Lipid biosynthesis Lipid metabolism Steroid biosynthesis Steroid metabolism Sterol biosynthesis Sterol metabolism
Cellular component	Membrane
Coding sequence diversity	Polymorphism
Domain	Transmembrane Transmembrane helix
Ligand	Heme Iron Metal-binding NADP
Molecular function	Monooxygenase Oxidoreductase
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological_process	sterol biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred from electronic annotation. Source: InterPro iron ion binding Inferred from electronic annotation. Source: InterPro sterol 14-demethylase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 481

481

Sterol 14-alpha demethylase

PRO_0000389527

Regions

Transmembrane

1 – 21

21

Helical; Potential

Sites

Metal binding

422

1

Iron (heme axial ligand) By similarity UniProtKB P0A512

Natural variations

Natural variant

62

1

D → E in allele 2. Ref.1 Ref.3

Natural variant

117

1

A → S in allele 2. Ref.1 Ref.3

Natural variant

160

1

E → K in allele 2. Ref.1 Ref.3

Experimental info

Mutagenesis

105

1

I → F: Increases activity on norlanosterol and obtusifoliol. Ref.2

Sequence conflict

9

1

A → G in AAW47718. Ref.2

Sequence conflict

9

1

A → G in EAN98359. Ref.3

Secondary structure

1

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481

Helix Strand Turn

Details...

Beta strand

29 – 31

3

Beta strand

34 – 36

3

Helix

39 – 47

9

Helix

52 – 62

11

Beta strand

66 – 74

9

Beta strand

76 – 80

5

Helix

83 – 85

3

Helix

86 – 90

5

Turn

94 – 96

3

Beta strand

97 – 99

3

Helix

100 – 103

4

Helix

104 – 106

3

Helix

107 – 110

4

Turn

112 – 114

3

Helix

115 – 117

3

Turn

119 – 121

3

Helix

122 – 133

12

Turn

136 – 141

6

Helix

142 – 157

16

Beta strand

160 – 166

7

Helix

167 – 183

17

Helix

186 – 191

6

Helix

194 – 202

9

Turn

203 – 206

4

Helix

210 – 218

9

Helix

230 – 249

20

Turn

252 – 254

3

Helix

261 – 267

7

Beta strand

271 – 273

3

Helix

278 – 308

31

Helix

310 – 312

3

Helix

313 – 323

11

Beta strand

324 – 326

3

Helix

332 – 337

6

Helix

340 – 352

13

Beta strand

359 – 365

7

Beta strand

367 – 369

3

Beta strand

372 – 374

3

Beta strand

379 – 382

4

Helix

384 – 387

4

Turn

391 – 393

3

Beta strand

394 – 396

3

Helix

418 – 420

3

Helix

425 – 442

18

Beta strand

443 – 451

9

Beta strand

459 – 461

3

Helix

466 – 469

4

Beta strand

470 – 475

6

Sequences

	Sequence		Length	Mass (Da)
	Q7Z1V1 [UniParc]. Last modified October 1, 2003. Version 1. Checksum: C83BA5243C959151	FASTA	481	54,683
	10 20 30 40 50 60 MFIEAIVLAL TALILYSVYS VKSFNTTRPT DPPVYPVTVP FLGHIVQFGK NPLEFMQRCK 70 80 90 100 110 120 RDLKSGVFTI SIGGQRVTIV GDPHEHSRFF SPRNEILSPR EVYTIMTPVF GEGVAYAAPY 130 140 150 160 170 180 PRMREQLNFL AEELTIAKFQ NFVPAIQHEV RKFMAENWKE DEGVINLLED CGAMIINTAC 190 200 210 220 230 240 QCLFGEDLRK RLNARHFAQL LSKMESSLIP AAVFMPWLLR LPLPQSARCR EARAELQKIL 250 260 270 280 290 300 GEIIVAREKE EASKDNNTSD LLGGLLKAVY RDGTRMSLHE VCGMIVAAMF AGQHTSTITT 310 320 330 340 350 360 SWSMLHLMHP KNKKWLDKLH KEIDEFPAQL NYDNVMDEMP FAERCVRESI RRDPPLLMVM 370 380 390 400 410 420 RMVKAEVKVG SYVVPKGDII ACSPLLSHHD EEAFPNPRLW DPERDEKVDG AFIGFGAGVH 430 440 450 460 470 480 KCIGQKFALL QVKTILATAF REYDFQLLRD EVPDPDYHTM VVGPTLNQCL VKYTRKKKLP S

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning and analysis of Trypanosoma cruzi lanosterol 14alpha-demethylase." Buckner F.S., Joubert B.M., Boyle S.M., Eastman R.T., Verlinde C.L.M.J., Matsuda S.P.T. Mol. Biochem. Parasitol. 132:75-81(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELES 1 AND 2), DEVELOPMENTAL STAGE. Strain: Tulahuen.
[2]	"CYP51 from Trypanosoma cruzi: a phyla-specific residue in the B' helix defines substrate preferences of sterol 14alpha-demethylase." Lepesheva G.I., Zaitseva N.G., Nes W.D., Zhou W., Arase M., Liu J., Hill G.C., Waterman M.R. J. Biol. Chem. 281:3577-3585(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ALLELE 1), FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ILE-105.
[3]	"The genome sequence of Trypanosoma cruzi, etiologic agent of Chagas disease." El-Sayed N.M.A., Myler P.J., Bartholomeu D.C., Nilsson D., Aggarwal G., Tran A.-N., Ghedin E., Worthey E.A., Delcher A.L., Blandin G., Westenberger S.J., Caler E., Cerqueira G.C., Branche C., Haas B., Anupama A., Arner E., Aslund L. , Attipoe P., Bontempi E., Bringaud F., Burton P., Cadag E., Campbell D.A., Carrington M., Crabtree J., Darban H., da Silveira J.F., de Jong P., Edwards K., Englund P.T., Fazelina G., Feldblyum T., Ferella M., Frasch A.C., Gull K., Horn D., Hou L., Huang Y., Kindlund E., Klingbeil M., Kluge S., Koo H., Lacerda D., Levin M.J., Lorenzi H., Louie T., Machado C.R., McCulloch R., McKenna A., Mizuno Y., Mottram J.C., Nelson S., Ochaya S., Osoegawa K., Pai G., Parsons M., Pentony M., Pettersson U., Pop M., Ramirez J.L., Rinta J., Robertson L., Salzberg S.L., Sanchez D.O., Seyler A., Sharma R., Shetty J., Simpson A.J., Sisk E., Tammi M.T., Tarleton R., Teixeira S., Van Aken S., Vogt C., Ward P.N., Wickstead B., Wortman J., White O., Fraser C.M., Stuart K.D., Andersson B. Science 309:409-415(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ALLELES 1 AND 2). Strain: CL Brener.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AY283022 Genomic DNA. Translation: AAP33131.1.
AY283023 Genomic DNA. Translation: AAP33132.1.
AY856083 Genomic DNA. Translation: AAW47718.1.
AAHK01000021 Genomic DNA. Translation: EAN99368.1.
AAHK01000058 Genomic DNA. Translation: EAN98359.1.

RefSeq

XP_820210.1. XM_815117.1.
XP_821219.1. XM_816126.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2WUZ	X-ray	2.35	A/B	22-481	[»]
2WX2	X-ray	2.27	A/B	22-481	[»]
3K1O	X-ray	2.89	A	32-481	[»]
3KHM	X-ray	2.85	A	32-481	[»]
3KSW	X-ray	3.05	A	32-481	[»]

ProteinModelPortal

Q7Z1V1.

ModBase

Search...

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

GeneID

3552837.
3554116.

KEGG

tcr:506297.260.
tcr:510101.50.

Phylogenomic databases

KO

K05917.

ProtClustDB

CLSZ2443033.

Enzyme and pathway databases

UniPathway

UPA00770; UER00754.

Family and domain databases

Gene3D

1.10.630.10. 1 hit.

InterPro

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

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

BindingDB

Q7Z1V1.

ChEMBL

CHEMBL1075110.

EvolutionaryTrace

Q7Z1V1.

Entry information

Entry name

CP51_TRYCC

Accession

Primary (citable) accession number: Q7Z1V1
Secondary accession number(s): Q5I4E1, Q7Z1V0

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 24, 2009
Last sequence update:	October 1, 2003
Last modified:	May 1, 2013
This is version 64 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)