P05108 (CP11A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cholesterol side-chain cleavage enzyme, mitochondrial
EC=1.14.15.6

Alternative name(s):
CYPXIA1
Cholesterol desmolase
Cytochrome P450 11A1
Cytochrome P450(scc)

Gene names

Name:	CYP11A1
Synonyms:	CYP11A

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	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 the cause of adrenal insufficiency congenital with 46,XY sex reversal (AICSR) [MIM:613743]. A rare disorder that can present as acute adrenal insufficiency in infancy or childhood. ACTH and plasma renin activity are elevated and adrenal steroids are inappropriately low or absent; the 46,XY patients have female external genitalia, sometimes with clitoromegaly. The phenotypic spectrum ranges from prematurity, complete underandrogenization, and severe early-onset adrenal failure to term birth with clitoromegaly and later-onset adrenal failure. Patients with congenital adrenal insufficiency do not manifest the massive adrenal enlargement typical of congenital lipoid adrenal hyperplasia. Ref.11 Ref.12 Ref.13 Ref.14 Ref.15
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	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological process	cholesterol metabolic process Inferred from mutant phenotype Ref.14. Source: UniProtKB vitamin D metabolic process Inferred from sequence or structural similarity. Source: UniProtKB xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular component	mitochondrial matrix Traceable author statement. Source: Reactome
Molecular function	cholesterol monooxygenase (side-chain-cleaving) activity Inferred from direct assay Ref.11Ref.14. 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

141

1

L → W in AICSR; reduced activity. Ref.14

VAR_065241

Natural variant

189

1

A → V in AICSR; no loss of activity. Ref.12

VAR_016949

Natural variant

222

1

L → P in AICSR; markedly reduced activity. Ref.15

VAR_065242

Natural variant

271

1

D → DGD in AICSR; complete loss of activity.

VAR_016950

Natural variant

314

1

E → K. Ref.9
Corresponds to variant rs6161 [ dbSNP | Ensembl ].

VAR_013944

Natural variant

353

1

R → W in AICSR; loss of activity. Ref.12

VAR_016951

Natural variant

359

1

A → V in AICSR; markedly reduced activity. Ref.13

VAR_065243

Natural variant

415

1

V → E in AICSR; complete loss of activity. Ref.14

VAR_065244

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

Secondary structure

1

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521

Helix Strand Turn

Details...

Helix

48 – 50

3

Helix

60 – 68

9

Helix

74 – 84

11

Beta strand

88 – 92

5

Beta strand

97 – 101

5

Helix

104 – 112

9

Helix

124 – 132

9

Helix

144 – 158

15

Helix

161 – 164

4

Helix

167 – 188

22

Helix

199 – 214

16

Beta strand

223 – 225

3

Helix

228 – 242

15

Helix

243 – 247

5

Helix

252 – 258

7

Helix

260 – 290

31

Helix

302 – 305

4

Helix

313 – 325

13

Helix

329 – 344

16

Helix

346 – 362

17

Helix

367 – 370

4

Helix

375 – 387

13

Beta strand

390 – 392

3

Beta strand

394 – 397

4

Beta strand

402 – 404

3

Beta strand

407 – 409

3

Beta strand

414 – 417

4

Turn

419 – 421

3

Turn

426 – 428

3

Beta strand

429 – 431

3

Helix

437 – 440

4

Turn

445 – 451

7

Helix

466 – 482

17

Beta strand

483 – 486

4

Beta strand

496 – 502

7

Beta strand

510 – 513

4

Sequences

	Sequence		Length	Mass (Da)
	P05108 [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 AICSR 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 AICSR VAL-189 AND TRP-353.
[13]	"Homozygous mutation of P450 side-chain cleavage enzyme gene (CYP11A1) in 46, XY patient with adrenal insufficiency, complete sex reversal, and agenesis of corpus callosum." al Kandari H., Katsumata N., Alexander S., Rasoul M.A. J. Clin. Endocrinol. Metab. 91:2821-2826(2006) [PubMed: 16705068] [Abstract] Cited for: VARIANT AICSR VAL-359, CHARACTERIZATION OF VARIANT AICSR VAL-359.
[14]	"Severe combined adrenal and gonadal deficiency caused by novel mutations in the cholesterol side chain cleavage enzyme, P450scc." Kim C.J., Lin L., Huang N., Quigley C.A., Avruskin T.W., Achermann J.C., Miller W.L. J. Clin. Endocrinol. Metab. 93:696-702(2008) [PubMed: 18182448] [Abstract] Cited for: VARIANTS AICSR TRP-141 AND GLU-415, CHARACTERIZATION OF VARIANTS AICSR TRP-141 AND GLU-415.
[15]	"A novel homozygous mutation in CYP11A1 gene is associated with late-onset adrenal insufficiency and hypospadias in a 46,XY patient." Rubtsov P., Karmanov M., Sverdlova P., Spirin P., Tiulpakov A. J. Clin. Endocrinol. Metab. 94:936-939(2009) [PubMed: 19116240] [Abstract] Cited for: VARIANT AICSR PRO-222, CHARACTERIZATION OF VARIANT AICSR PRO-222.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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. NM_000781.2.
NP_001093243.1. NM_001099773.1.

UniGene

Hs.303980.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3N9Y	X-ray	2.10	A/B	41-521	[»]
3N9Z	X-ray	2.17	A/B	41-521	[»]
3NA0	X-ray	2.50	A/B	44-514	[»]
3NA1	X-ray	2.25	A/B	41-521	[»]

ProteinModelPortal

P05108.

SMR

P05108. Positions 44-514.

ModBase

Search...

Protein-protein interaction databases

MINT

MINT-1200919.

STRING

P05108.

Polymorphism databases

DMDM

143811381.

Proteomic databases

PRIDE

P05108.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000268053; ENSP00000268053; ENSG00000140459.

GeneID

1583.

KEGG

hsa:1583.

UCSC

uc002axt.2. human.

Organism-specific databases

CTD

1583.

GeneCards

GC15M074630.

H-InvDB

HIX0012428.

HGNC

HGNC:2590. CYP11A1.

HPA

HPA016436.

MIM

118485. gene.
613743. phenotype.

neXtProt

NX_P05108.

Orphanet

168558. 46,XY disorder of sex development - adrenal insufficiency.
90790. Congenital lipoid adrenal hyperplasia.

PharmGKB

PA27089.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG13335.

HOGENOM

HBG444565.

HOVERGEN

HBG051098.

InParanoid

P05108.

OMA

DIKANVT.

OrthoDB

EOG4GXFMF.

PhylomeDB

P05108.

Enzyme and pathway databases

BioCyc

MetaCyc:HS06719-MONOMER.

Reactome

REACT_111217. Metabolism.
REACT_15493. Steroid hormones.
REACT_22258. 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.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
[Graphical view]

Gene3D

G3DSA:1.10.630.10. Cyt_P450. 1 hit.

KO

K00498.

Pfam

PF00067. p450. 1 hit.
[Graphical view]

PRINTS

PR00463. EP450I.
PR00385. P450.

SUPFAM

SSF48264. Cytochrome_P450. 1 hit.

PROSITE

PS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

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:	January 25, 2012
This is version 137 of the entry and version 2 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.