Reviewed, UniProtKB/Swiss-Prot P05108 (CP11A_HUMAN)

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

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.

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.7
Involvement in disease	Defects in CYP11A1 are a cause of congenital adrenal insufficiency (CAI). Ref.12 Defects in CYP11A1 are a cause of congenital lipoid adrenal hyperplasia (CLAH) [MIM:201710]; also known as 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.11
Sequence similarities	Belongs to the cytochrome P450 family.

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.11 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.11 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...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 39	39	Mitochondrion
	Chain	40 – 521	482	Cholesterol side-chain cleavage enzyme, mitochondrial		PRO_0000003585
Sites
	Metal binding	462	1	Iron (heme axial ligand)
Natural variations
	Natural variant	189	1	A → V in CAI; no loss of activity. Ref.12		VAR_016949
	Natural variant	271	1	D → DGD in CLAH; complete loss of activity.		VAR_016950
	Natural variant	314	1	E → K: dbSNP rs6161. Ref.9		VAR_013944
	Natural variant	353	1	R → W in CAI; loss of activity. Ref.12		VAR_016951
Experimental info
	Sequence conflict	16	1	C → Y in AAA52162. Ref.1
	Sequence conflict	274	1	F → L in CAA28965. Ref.2
	Sequence conflict	283	1	N → H in AAA36404. Ref.8
	Sequence conflict	301	1	I → M in AAA52162. Ref.1
	Sequence conflict	301	1	I → M in AAA36404. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	P05108-1 [UniParc]. Last modified April 3, 2007. Version 2. Checksum: AB0501E7A5665D8B	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

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]	"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]. Tissue: Testis.
[4]	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].
[5]	"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.
[6]	Chung B.-C. Submitted (JAN-1989) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-89.
[7]	"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.
[8]	"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.
[9]	"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.
[10]	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)
[11]	"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.
[12]	"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.

Cross-references

Sequence databases
EMBLGenBankDDBJ	M14565 mRNA. Translation: AAA52162.1. X05367 , X05368, X05369, X05370, X05371, X05372, X05373, X05374 Genomic DNA. Translation: CAA28965.1. AK292300 mRNA. Translation: BAF84989.1. CH471136 Genomic DNA. Translation: EAW99342.1. 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...
Protein-protein interaction databases
STRING	P05108.
Proteomic databases
PRIDE	P05108.
Genome annotation databases
Ensembl	ENST00000268053; ENSP00000268053; ENSG00000140459; Homo sapiens. [Genome view] ENST00000358632; ENSP00000351455; ENSG00000140459; Homo sapiens. [Genome view] ENST00000416978; ENSP00000388018; ENSG00000140459; Homo sapiens. [Genome view] ENST00000433240; ENSP00000387487; ENSG00000140459; Homo sapiens. [Genome view] ENST00000435365; ENSP00000391081; ENSG00000140459; Homo sapiens. [Genome view] ENST00000450547; ENSP00000402064; ENSG00000140459; Homo sapiens. [Genome view] ENST00000452422; ENSP00000391041; ENSG00000140459; Homo sapiens. [Genome view] ENST00000455006; ENSP00000407256; ENSG00000140459; Homo sapiens. [Genome view]
GeneID	1583.
KEGG	hsa:1583.
UCSC	uc002axt.2. human.
Organism-specific databases
CTD	1583.
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	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.
Genevestigator	P05108.
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...

Entry information

Entry name

CP11A_HUMAN

Accession

Primary (citable) accession number: P05108
Secondary accession number(s): A8K8D5 , Q15081, Q16805, Q8N1A7

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	April 3, 2007
Last modified:	November 3, 2009
This is version 115 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.