Cytochrome P450 11B2, mitochondrial precursor

Contribute

Send feedback

Read comments (0) or add your own

Reviewed, UniProtKB/Swiss-Prot P19099 (C11B2_HUMAN)

Last modified July 7, 2009. Version 109. History...

Clusters with 100%, 90%, 50% identity |

Documents (5) |

Third-party data |

Customize display

text xml rdf/xml gff fasta

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

Hide | Top

Names and origin

Protein names

Recommended name:
    Cytochrome P450 11B2, mitochondrial
Alternative name(s):
    CYPXIB2
    P-450Aldo
    Aldosterone synthase
      Short name=ALDOS
    EC=1.14.15.4
    EC=1.14.15.5
    Aldosterone-synthesizing enzyme
    Steroid 18-hydroxylase
    P-450C18

Gene names

Name:

CYP11B2

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

Hide | Top

Protein attributes

Sequence length	503 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

Hide | Top

General annotation (Comments)

Function	Preferentially catalyzes the conversion of 11-deoxycorticosterone to aldosterone via corticosterone and 18-hydroxycorticosterone.
Catalytic activity	A steroid + reduced adrenal ferredoxin + O₂ = an 11-beta-hydroxysteroid + oxidized adrenal ferredoxin + H₂O. Corticosterone + reduced adrenal ferredoxin + O₂ = 18-hydroxycorticosterone + oxidized adrenal ferredoxin + H₂O.
Cofactor	Heme group By similarity.
Subcellular location	Mitochondrion membrane.
Involvement in disease	Defects in CYP11B2 are the cause of corticosterone methyloxidase type 1 deficiency (CMO-1 deficiency) [MIM:203400]; also called aldosterone deficiency due to defect in 18-hydroxylase or aldosterone deficiency I. CMO-1 deficiency is an autosomal recessive disorder of aldosterone biosynthesis. There are two biochemically different forms of selective aldosterone deficiency be termed corticosterone methyloxidase (CMO) deficiency type 1 and type 2. In CMO-1 deficiency, aldosterone is undetectable in plasma, while its immediate precursor, 18-hydroxycorticosterone, is low or normal. Ref.7 Defects in CYP11B2 are the cause of corticosterone methyloxidase type 2 deficiency (CMO-2 deficiency) [MIM:610600]. CMO-2 is an autosomal recessive disorder of aldosterone biosynthesis. In CMO-2 deficiency, aldosterone can be low or normal, but at the expense of increased secretion of 18-hydroxycorticosterone. Consequently, patients have a greatly increased ratio of 18-hydroxycorticosterone to aldosterone and a low ratio of corticosterone to 18-hydroxycorticosterone in serum. An anti-Lepore-type fusion of the CYP11B2 and CYP11B1 genes is a cause of glucocorticoid-remediable aldosteronism (GRA) [MIM:103900]. Ref.7
Sequence similarities	Belongs to the cytochrome P450 family.

Hide | Top

Ontologies

Keywords
Biological process	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
Gene Ontology (GO)
Biological process	C21-steroid hormone biosynthetic process Ref.2 Inferred from direct assay. Source: UniProtKB aldosterone biosynthetic process Ref.2 Inferred from direct assay. Source: UniProtKB oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW potassium ion homeostasis Inferred from mutant phenotype. Source: UniProtKB regulation of blood volume by renal aldosterone Inferred from mutant phenotype. Source: UniProtKB renal water homeostasis Ref.2 Inferred by curator. Source: UniProtKB sodium ion homeostasis Inferred from mutant phenotype. Source: UniProtKB
Cellular component	mitochondrial inner membrane Ref.2 Inferred by curator. Source: UniProtKB
Molecular function	corticosterone 18-monooxygenase activity Inferred from electronic annotation. Source: EC electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Ref.2 Inferred by curator. Source: UniProtKB steroid 11-beta-monooxygenase activity Ref.2 Inferred from direct assay. Source: UniProtKB steroid binding Ref.2 Inferred by curator. Source: UniProtKB
Complete GO annotation...

Hide | Top

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Transit peptide

1 – 24

Mitochondrion

Chain

25 – 503

479

Cytochrome P450 11B2, mitochondrial

PRO_0000003597

Sites

Metal binding

450

Iron (heme axial ligand) By similarity

Natural variations

Natural variant

A → T: dbSNP rs6438. Ref.12

VAR_014151

Natural variant

R → Q: dbSNP rs6441. Ref.12 Ref.4 Ref.5 Ref.8 Ref.9 Ref.10 Ref.15 Ref.16

VAR_014152

Natural variant

140

N → NRL in CMO-1 deficiency; the enzyme is inactive.

VAR_018470

Natural variant

173

K → R: dbSNP rs4539. Ref.12 Ref.11 Ref.14

VAR_001266

Natural variant

181

R → W in CMO-2 deficiency; reduces 18-hydroxylase and abolishes 18-oxidase activities; leaves 11 beta-hydroxylase activity intact.

VAR_001267

Natural variant

185

T → I in CMO-2 deficiency.

VAR_018471

Natural variant

198

E → D in CMO-2 deficiency.

VAR_001268

Natural variant

222

N → T: dbSNP rs5308.

VAR_014643

Natural variant

248

I → T: dbSNP rs4547. Ref.12 Ref.14

VAR_014153

Natural variant

281

N → S: dbSNP rs4537. Ref.12 Ref.14

VAR_014154

Natural variant

339

I → T: dbSNP rs4544. Ref.12 Ref.14

VAR_014155

Natural variant

383

E → V: dbSNP rs5312.

VAR_014644

Natural variant

386

V → A in CMO-2 deficiency; small but consistent reduction in the production of 18-hydroxycorticosterone. dbSNP rs4541.

VAR_001269

Natural variant

403

V → E: dbSNP rs5315.

VAR_014645

Natural variant

435

G → S: dbSNP rs4545. Ref.12 Ref.14

VAR_014156

Natural variant

461

L → P in CMO-1 deficiency; abolishes the 18-hydroxylase activity required for conversion of 11-deoxycorticosterone to aldosterone.

VAR_018472

Natural variant

487

F → V: dbSNP rs5317.

VAR_014646

Natural variant

498

T → A in CMO-2 deficiency.

VAR_018473

Experimental info

Sequence conflict

S → C in AAA35741. Ref.1

Sequence conflict

I → M in AAA35741. Ref.1

Sequence conflict

119

Y → I in AAA35741. Ref.1

Sequence conflict

249

S → R in CAA38539. Ref.2

Sequence conflict

342

Q → K in AAA35741. Ref.1

Sequence conflict

438

F → L in AAA35741. Ref.1

Sequence conflict

470

H → R in AAA35741. Ref.1

Hide | Top

Sequences

Sequence

Length

Mass (Da)

Tools

P19099-1 [UniParc].

Last modified July 15, 1998. Version 3.
Checksum: 42BA671704CEE35D
Show »

FASTA

503

57,560

        10         20         30         40         50         60 
MALRAKAEVC VAAPWLSLQR ARALGTRAAR APRTVLPFEA MPQHPGNRWL RLLQIWREQG 

        70         80         90        100        110        120 
YEHLHLEMHQ TFQELGPIFR YNLGGPRMVC VMLPEDVEKL QQVDSLHPCR MILEPWVAYR 

       130        140        150        160        170        180 
QHRGHKCGVF LLNGPEWRFN RLRLNPDVLS PKAVQRFLPM VDAVARDFSQ ALKKKVLQNA 

       190        200        210        220        230        240 
RGSLTLDVQP SIFHYTIEAS NLALFGERLG LVGHSPSSAS LNFLHALEVM FKSTVQLMFM 

       250        260        270        280        290        300 
PRSLSRWISP KVWKEHFEAW DCIFQYGDNC IQKIYQELAF NRPQHYTGIV AELLLKAELS 

       310        320        330        340        350        360 
LEAIKANSME LTAGSVDTTA FPLLMTLFEL ARNPDVQQIL RQESLAAAAS ISEHPQKATT 

       370        380        390        400        410        420 
ELPLLRAALK ETLRLYPVGL FLERVVSSDL VLQNYHIPAG TLVQVFLYSL GRNAALFPRP 

       430        440        450        460        470        480 
ERYNPQRWLD IRGSGRNFHH VPFGFGMRQC LGRRLAEAEM LLLLHHVLKH FLVETLTQED 

       490        500 
IKMVYSFILR PGTSPLLTFR AIN

« Hide

Hide | Top

References

[1]	"Characterization of two genes encoding human steroid 11 beta-hydroxylase (P-450(11) beta)." Mornet E., Dupont J., Vitek A., White P.C. J. Biol. Chem. 264:20961-20967(1989) [PubMed: 2592361] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]	"Cloning and expression of a cDNA for human cytochrome P-450aldo as related to primary aldosteronism." Kawamoto T., Mitsuuchi Y., Ohnishi T., Ichikawa Y., Yokoyama Y., Sumimoto H., Toda K., Miyahara K., Kuribayashi I., Nakao K., Hosoda K., Yamamoto Y., Imura H., Shizuta Y. Biochem. Biophys. Res. Commun. 173:309-316(1990) [PubMed: 2256920] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Adrenal gland.
[3]	Kawamoto T., Miyahara K., Mitsuuchi Y., Ulick S., Shizuta Y. Submitted (JUN-1994) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Blood.
[4]	"Mutations in the human CYP11B2 (aldosterone synthase) gene causing corticosterone methyloxidase II deficiency." Pascoe L., Curnow K.M., Slutsker L., Roesler A., White P.C. Proc. Natl. Acad. Sci. U.S.A. 89:4996-5000(1992) [PubMed: 1594605] [Abstract] Cited for: VARIANTS CMO-2 DEFICIENCY TRP-181 AND ALA-386.
[5]	"Congenitally defective aldosterone biosynthesis in humans: the involvement of point mutations of the P-450C18 gene (CYP11B2) in CMO II deficient patients." Mitsuuchi Y., Kawamoto T., Naiki Y., Miyahara K., Toda K., Kuribayashi I., Orii T., Yasuda K., Miura K., Nakao K., Imura H., Ulick S., Shizuta Y. Biochem. Biophys. Res. Commun. 182:974-979(1992) [PubMed: 1346492] [Abstract] Cited for: VARIANTS CMO-2 DEFICIENCY TRP-181 AND ALA-386.
[6]	Erratum Mitsuuchi Y., Kawamoto T., Naiki Y., Miyahara K., Toda K., Kuribayashi I., Orii T., Yasuda K., Miura K., Nakao K., Imura H., Ulick S., Shizuta Y. Biochem. Biophys. Res. Commun. 184:1529-1530(1992)
[7]	"Congenitally defective aldosterone biosynthesis in humans: inactivation of the P-450(C18) gene (CYP11B2) due to nucleotide deletion in CMO I deficient patients." Mitsuuchi Y., Kawamoto T., Miyahara K., Ulick S., Morton D.H., Naiki Y., Kuribayashi I., Toda K., Hara T., Orii T., Yasuda K., Miura K., Yamamoto Y., Imura H., Shizuta Y. Biochem. Biophys. Res. Commun. 190:864-869(1993) [PubMed: 8439335] [Abstract] Cited for: DISEASE.
[8]	"CMO I deficiency caused by a point mutation in exon 8 of the human CYP11B2 gene encoding steroid 18-hydroxylase (P450C18)." Nomoto S., Massa G., Mitani F., Ishimura Y., Miyahara K., Toda K., Nagano I., Yamashiro T., Ogoshi S., Fukata J., Onishi S., Hashimoto K., Doi Y., Imura H., Shizuta Y. Biochem. Biophys. Res. Commun. 234:382-385(1997) [PubMed: 9177280] [Abstract] Cited for: VARIANT CMO-1 DEFICIENCY PRO-461.
[9]	"Mutation THR-185 ILE is associated with corticosterone methyl oxidase deficiency type II." Peter M., Buenger K., Solyom J., Sippell W.G. Eur. J. Pediatr. 157:378-381(1998) [PubMed: 9625333] [Abstract] Cited for: VARIANT CMO-2 DEFICIENCY ILE-185.
[10]	"Isolated aldosterone synthase deficiency caused by simultaneous E198D and V386A mutations in the CYP11B2 gene." Portrat-Doyen S., Tourniaire J., Richard O., Mulatero P., Aupetit-Faisant B., Curnow K.M., Pascoe L., Morel Y. J. Clin. Endocrinol. Metab. 83:4156-4161(1998) [PubMed: 9814506] [Abstract] Cited for: VARIANTS CMO-2 DEFICIENCY ASP-198 AND ALA-386.
[11]	"Genetic polymorphism of CYP11B2 gene and hypertension in Japanese." Tamaki S., Iwai N., Tsujita Y., Kinoshita M. Hypertension 33:266-270(1999) [PubMed: 9931115] [Abstract] Cited for: VARIANT ARG-173.
[12]	"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: VARIANTS THR-29; GLN-30; ARG-173; THR-248; SER-281; THR-339; ALA-386 AND SER-435.
[13]	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)
[14]	"Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis." Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A., Cooper R., Lipshutz R., Chakravarti A. Nat. Genet. 22:239-247(1999) [PubMed: 10391210] [Abstract] Cited for: VARIANTS ARG-173; THR-248; SER-281; THR-339; ALA-386 AND SER-435.
[15]	"Type 1 aldosterone synthase deficiency presenting in a middle-aged man." Kayes-Wandover K.M., Schindler R.E.L., Taylor H.C., White P.C. J. Clin. Endocrinol. Metab. 86:1008-1012(2001) [PubMed: 11238478] [Abstract] Cited for: VARIANT CMO-1 DEFICIENCY ARG-LEU-140 INS.
[16]	"A compound heterozygote case of type II aldosterone synthase deficiency." Dunlop F.M., Crock P.A., Montalto J., Funder J.W., Curnow K.M. J. Clin. Endocrinol. Metab. 88:2518-2526(2003) [PubMed: 12788848] [Abstract] Cited for: VARIANTS CMO-2 DEFICIENCY ILE-185 AND ALA-498.
+	Additional computationally mapped references.

Hide | Top

Web resources

GeneReviews

Wikipedia

CYP11B2 entry

Hide | Top

Cross-references

Sequence databases
	M32881, M32864, M32880 Genomic DNA. Translation: AAA35741.1. X54741 mRNA. Translation: CAA38539.1. D13752 Genomic DNA. Translation: BAA02899.1.
IPI	IPI00290116.
PIR	B34181.
RefSeq	NP_000489.3.
UniGene	Hs.632054
3D structure databases
HSSP	HSSP built from PDB template 1SCC based on UniProtKB P00189.
ModBase	Search...
Proteomic databases
PRIDE	P19099.
Genome annotation databases
Ensembl	ENSG00000179142. Homo sapiens. [Contig view]
GeneID	1585.
KEGG	hsa:1585.
UCSC	uc003yxk.1. human.
Organism-specific databases
GeneCards	GC08M143988.
HGNC	HGNC:2592. CYP11B2.
MIM	103900. phenotype. 124080. gene. 203400. phenotype. 610600. phenotype.
Orphanet	85142. Conn's syndrome. 99762. Corticosterone methyl-oxydase deficiency, type I (CMO I). 99765. Corticosterone methyl-oxydase deficiency, type II (CMO II). 403. Hyperaldosteronism, familial, type 1. 404. Hyperaldosteronism, familial, type 2. 427. Hypoaldosteronism, familial.
PharmGKB	PA134.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P19099.
HOVERGEN	P19099.
OMA	P19099. EHLHLEM.
Enzyme and pathway databases
BRENDA	1.14.15.4. 247. 1.14.15.5. 247.
Reactome	REACT_13433. Biological oxidations. REACT_15314. Hormone biosynthesis. REACT_602. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	P19099.
Bgee	P19099.
CleanEx	HS_CYP11B2.
GermOnline	ENSG00000179142. Homo sapiens.
Family and domain databases
InterPro	IPR001128. Cyt_P450. IPR017973. Cyt_P450_C. IPR017972. Cyt_P450_CS. IPR002399. Cyt_P450_mit_N. [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	PR00408. MITP450. PR00385. P450.
PROSITE	PS00086. CYTOCHROME_P450. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00796. Candesartan. DB01011. Metyrapone.
NextBio	6515.
SOURCE	Search...

Hide | Top

Entry information

Entry name

C11B2_HUMAN

Accession

Primary (citable) accession number: P19099
Secondary accession number(s): Q16726

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	July 15, 1998
Last modified:	July 7, 2009
This is version 109 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Hide | Top

Relevant documents

Human chromosome 8

Human chromosome 8: 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

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

Web resources

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