Cholesterol side-chain cleavage enzyme, mitochondrial precursor

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Reviewed, UniProtKB/Swiss-Prot P05108 (CP11A_HUMAN)

Last modified July 7, 2009. Version 111. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Cholesterol side-chain cleavage enzyme, mitochondrial
    EC=1.14.15.6
Alternative name(s):
    Cytochrome P450 11A1
    CYPXIA1
    P450(scc)
    Cholesterol desmolase

Gene names

Name:	CYP11A1
Synonyms:	CYP11A

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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Protein attributes

Sequence length	521 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

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General annotation (Comments)

Function	Catalyzes the side-chain cleavage reaction of cholesterol to pregnenolone.
Catalytic activity	Cholesterol + reduced adrenal ferredoxin + O₂ = pregnenolone + 4-methylpentanal + oxidized adrenal ferredoxin + H₂O.
Cofactor	Heme group By similarity.
Pathway	Lipid metabolism; C21-steroid hormone metabolism.
Subcellular location	Mitochondrion membrane.
Induction	By 8-bromo cyclic AMP. Ref.5
Involvement in disease	Defects in CYP11A1 are a cause of congenital adrenal insufficiency (CAI). Ref.10 Defects in CYP11A1 are a cause of congenital lipoid adrenal hyperplasia (CLAH) [MIM:201710]; also called lipoid CAH. CLAH is the most severe form of adrenal hyperplasia. This autosomal recessive and potentially lethal condition includes the onset of profound adrenocortical insufficiency shortly after birth, hyperpigmentation reflecting increased production of pro-opiomelanocortin, elevated plasma renin activity as a consequence of reduced aldosterone synthesis, and male pseudohermaphroditism resulting from deficient fetal testicular testosterone synthesis. CLAH is a rare disease, except in Japan and Korea where it accounts for a significant percentage of cases of congenital adrenal hyperplasia. Ref.9
Sequence similarities	Belongs to the cytochrome P450 family.

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Ontologies

Keywords
Biological process	Cholesterol metabolism Lipid metabolism Steroid metabolism Steroidogenesis
Cellular component	Membrane Mitochondrion
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transit peptide
Ligand	Heme Iron Metal-binding
Molecular function	Monooxygenase Oxidoreductase
Technical term	Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	C21-steroid hormone biosynthetic process Ref.9 Inferred from direct assay. Source: UniProtKB cholesterol metabolic process Inferred from mutant phenotype. Source: UniProtKB oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW vitamin D metabolic process Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	mitochondrial membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	cholesterol monooxygenase (side-chain-cleaving) activity Ref.9 Inferred from direct assay. Source: UniProtKB electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 39

Mitochondrion

Chain

40 – 521

482

Cholesterol side-chain cleavage enzyme, mitochondrial

PRO_0000003585

Sites

Metal binding

462

Iron (heme axial ligand)

Natural variations

Natural variant

189

A → V in CAI; no loss of activity. Ref.10

VAR_016949

Natural variant

271

D → DGD in CLAH; complete loss of activity.

VAR_016950

Natural variant

314

E → K: dbSNP rs6161. Ref.7

VAR_013944

Natural variant

353

R → W in CAI; loss of activity. Ref.10

VAR_016951

Experimental info

Sequence conflict

C → Y in AAA52162. Ref.1

Sequence conflict

274

F → L in CAA28965. Ref.2

Sequence conflict

283

N → H in AAA36404. Ref.6

Sequence conflict

301

I → M in AAA52162. Ref.1

Sequence conflict

301

I → M in AAA36404. Ref.6

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Sequences

Sequence

Length

Mass (Da)

Tools

P05108-1 [UniParc].

Last modified April 3, 2007. Version 2.
Checksum: AB0501E7A5665D8B
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FASTA

521

60,102

        10         20         30         40         50         60 
MLAKGLPPRS VLVKGCQTFL SAPREGLGRL RVPTGEGAGI STRSPRPFNE IPSPGDNGWL 

        70         80         90        100        110        120 
NLYHFWRETG THKVHLHHVQ NFQKYGPIYR EKLGNVESVY VIDPEDVALL FKSEGPNPER 

       130        140        150        160        170        180 
FLIPPWVAYH QYYQRPIGVL LKKSAAWKKD RVALNQEVMA PEATKNFLPL LDAVSRDFVS 

       190        200        210        220        230        240 
VLHRRIKKAG SGNYSGDISD DLFRFAFESI TNVIFGERQG MLEEVVNPEA QRFIDAIYQM 

       250        260        270        280        290        300 
FHTSVPMLNL PPDLFRLFRT KTWKDHVAAW DVIFSKADIY TQNFYWELRQ KGSVHHDYRG 

       310        320        330        340        350        360 
ILYRLLGDSK MSFEDIKANV TEMLAGGVDT TSMTLQWHLY EMARNLKVQD MLRAEVLAAR 

       370        380        390        400        410        420 
HQAQGDMATM LQLVPLLKAS IKETLRLHPI SVTLQRYLVN DLVLRDYMIP AKTLVQVAIY 

       430        440        450        460        470        480 
ALGREPTFFF DPENFDPTRW LSKDKNITYF RNLGFGWGVR QCLGRRIAEL EMTIFLINML 

       490        500        510        520 
ENFRVEIQHL SDVGTTFNLI LMPEKPISFT FWPFNQEATQ Q

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References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human cholesterol side-chain cleavage enzyme, P450scc: cDNA cloning, assignment of the gene to chromosome 15, and expression in the placenta." Chung B.-C., Matteson K.J., Voutilainen R., Mohandas T.K., Miller W.L. Proc. Natl. Acad. Sci. U.S.A. 83:8962-8966(1986) [PubMed: 3024157] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Gene structure of human cytochrome P-450(SCC), cholesterol desmolase." Morohashi K., Sogawa K., Omura T., Fujii-Kuriyama Y. J. Biochem. 101:879-887(1987) [PubMed: 3038854] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Placenta.
[3]	"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]. Tissue: Brain.
[4]	Chung B.-C. Submitted (JAN-1989) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-89.
[5]	"Regulated expression of cytochrome P-450scc (cholesterol-side-chain cleavage enzyme) in cultured cell lines detected by antibody against bacterially expressed human protein." Hu M.C., Guo I.C., Lin J.H., Chung B.-C. Biochem. J. 274:813-817(1991) [PubMed: 1849407] [Abstract] Cited for: PROTEIN SEQUENCE OF 51-54, INDUCTION. Tissue: Choriocarcinoma.
[6]	"Study of cholesterol side-chain cleavage (20,22 desmolase) deficiency causing congenital lipoid adrenal hyperplasia using bovine-sequence P450scc oligodeoxyribonucleotide probes." Matteson K.J., Chung B.-C., Urdea M.S., Miller W.L. Endocrinology 118:1296-1305(1986) [PubMed: 2419119] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 283-521.
[7]	"Characterization of single-nucleotide polymorphisms in coding regions of human genes." Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 22:231-238(1999) [PubMed: 10391209] [Abstract] Cited for: VARIANT LYS-314.
[8]	Erratum Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., Lander E.S. Nat. Genet. 23:373-373(1999)
[9]	"Heterozygous mutation in the cholesterol side chain cleavage enzyme (P450scc) gene in a patient with 46,XY sex reversal and adrenal insufficiency." Tajima T., Fujieda K., Kouda N., Nakae J., Miller W.L. J. Clin. Endocrinol. Metab. 86:3820-3825(2001) [PubMed: 11502818] [Abstract] Cited for: VARIANT CLAH GLY-ASP-271 INS.
[10]	"Compound heterozygous mutations in the cholesterol side-chain cleavage enzyme gene (CYP11A) cause congenital adrenal insufficiency in humans." Katsumata N., Ohtake M., Hojo T., Ogawa E., Hara T., Sato N., Tanaka T. J. Clin. Endocrinol. Metab. 87:3808-3813(2002) [PubMed: 12161514] [Abstract] Cited for: VARIANTS CAI VAL-189 AND TRP-353.
+	Additional computationally mapped references.

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Cross-references

Sequence databases
	M14565 mRNA. Translation: AAA52162.1. X05367 X05374 Genomic DNA. Translation: CAA28965.1. BC032329 mRNA. Translation: AAH32329.1. X14257 Genomic DNA. Translation: CAA32471.1. M28253 mRNA. Translation: AAA36404.1.
IPI	IPI00295771.
PIR	A25922.
RefSeq	NP_000772.2. NP_001093243.1.
UniGene	Hs.303980
3D structure databases
HSSP	HSSP built from PDB template 1SCC based on UniProtKB P00189.
ModBase	Search...
Proteomic databases
PRIDE	P05108.
Genome annotation databases
Ensembl	ENSG00000140459. Homo sapiens. [Contig view]
GeneID	1583.
KEGG	hsa:1583.
UCSC	uc002axt.2. human.
Organism-specific databases
GeneCards	GC15M072417.
H-InvDB	HIX0012428.
HGNC	HGNC:2590. CYP11A1.
HPA	HPA016436.
MIM	118485. gene. 201710. phenotype.
Orphanet	418. Congenital adrenal hyperplasia.
PharmGKB	PA27089.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P05108.
OMA	P05108. NQEVMAP.
Enzyme and pathway databases
BRENDA	1.14.15.6. 247.
Reactome	REACT_13433. Biological oxidations. REACT_15314. Hormone biosynthesis. REACT_602. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	P05108.
Bgee	P05108.
CleanEx	HS_CYP11A1.
GermOnline	ENSG00000140459. Homo sapiens.
Family and domain databases
InterPro	IPR001128. Cyt_P450. IPR017973. Cyt_P450_C. IPR017972. Cyt_P450_CS. IPR002401. Cyt_P450_E_grp-I. [Graphical view]
Gene3D	G3DSA:1.10.630.10. Cyt_P450. 1 hit.
PANTHER	PTHR19383. Cyt_P450. 1 hit.
Pfam	PF00067. p450. 1 hit. [Graphical view]
PRINTS	PR00463. EP450I. PR00385. P450.
PROSITE	PS00086. CYTOCHROME_P450. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00357. Aminoglutethimide. DB00169. Cholecalciferol. DB00501. Cimetidine. DB00257. Clotrimazole. DB01396. Digitoxin. DB00390. Digoxin. DB00603. Medroxyprogesterone. DB01092. Ouabain. DB00396. Progesterone. DB00624. Testosterone. DB01108. Trilostane.
NextBio	6503.
SOURCE	Search...

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Entry information

Entry name

CP11A_HUMAN

Accession

Primary (citable) accession number: P05108
Secondary accession number(s): Q15081, Q16805, Q8N1A7

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	April 3, 2007
Last modified:	July 7, 2009
This is version 111 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 15

Human chromosome 15: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PATHWAY comments

Index of metabolic and biosynthesis pathways

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Sites

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents