P19099 (C11B2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cytochrome P450 11B2, mitochondrial

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

Gene names

Name:

CYP11B2

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	503 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	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 known as 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.9 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. Defects in CYP11B2 are a cause of familial hyperaldosteronism type 1 (FH1) [MIM:103900]. It is a disorder characterized by hypertension, variable hyperaldosteronism, and abnormal adrenal steroid production, including 18-oxocortisol and 18-hydroxycortisol. There is significant phenotypic heterogeneity, and some individuals never develop hypertension. Note=The molecular defect causing hyperaldosteronism familial type 1 is an anti-Lepore-type fusion of the CYP11B1 and CYP11B2 genes. The hybrid gene has the promoting part of CYP11B1, ACTH-sensitive, and the coding part of CYP11B2. Ref.9
Sequence similarities	Belongs to the cytochrome P450 family.

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 Reference proteome
Gene Ontology (GO)
Biological process	aldosterone biosynthetic process Inferred from mutant phenotype. Source: UniProtKB cellular response to hormone stimulus Inferred from expression pattern. Source: UniProtKB cellular response to potassium ion Inferred from expression pattern. Source: UniProtKB cortisol biosynthetic process Inferred from mutant phenotype. Source: UniProtKB potassium ion homeostasis Inferred from mutant phenotype. Source: BHF-UCL regulation of blood volume by renal aldosterone Inferred from mutant phenotype. Source: BHF-UCL renal water homeostasis Inferred by curator Ref.2. Source: BHF-UCL sodium ion homeostasis Inferred from mutant phenotype. Source: BHF-UCL xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular component	mitochondrial inner membrane Inferred by curator Ref.2. Source: BHF-UCL
Molecular function	corticosterone 18-monooxygenase activity Inferred from electronic annotation. Source: EC electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred by curator Ref.2. Source: BHF-UCL steroid 11-beta-monooxygenase activity Inferred from direct assay Ref.2. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 24	24	Mitochondrion
	Chain	25 – 503	479	Cytochrome P450 11B2, mitochondrial		PRO_0000003597
Sites
	Metal binding	450	1	Iron (heme axial ligand) By similarity
Natural variations
	Natural variant	29	1	A → T. Ref.14 Corresponds to variant rs6438 [ dbSNP | Ensembl ].		VAR_014151
	Natural variant	30	1	R → Q. Ref.14 Corresponds to variant rs6441 [ dbSNP | Ensembl ].		VAR_014152
	Natural variant	140	1	N → NRL in CMO-1 deficiency; the enzyme is inactive.		VAR_018470
	Natural variant	173	1	K → R. Ref.13 Ref.14 Ref.16 Corresponds to variant rs4539 [ dbSNP | Ensembl ].		VAR_001266
	Natural variant	181	1	R → W in CMO-2 deficiency; reduces 18-hydroxylase and abolishes 18-oxidase activities; leaves 11 beta-hydroxylase activity intact. Ref.6 Ref.7 Corresponds to variant rs28931609 [ dbSNP | Ensembl ].		VAR_001267
	Natural variant	185	1	T → I in CMO-2 deficiency. Ref.11 Ref.18		VAR_018471
	Natural variant	198	1	E → D in CMO-2 deficiency. Ref.12		VAR_001268
	Natural variant	222	1	N → T. Corresponds to variant rs5308 [ dbSNP | Ensembl ].		VAR_014643
	Natural variant	248	1	I → T. Ref.14 Ref.16 Corresponds to variant rs4547 [ dbSNP | Ensembl ].		VAR_014153
	Natural variant	281	1	N → S. Ref.14 Ref.16 Corresponds to variant rs4537 [ dbSNP | Ensembl ].		VAR_014154
	Natural variant	339	1	I → T. Ref.14 Ref.16 Corresponds to variant rs4544 [ dbSNP | Ensembl ].		VAR_014155
	Natural variant	383	1	E → V. Corresponds to variant rs5312 [ dbSNP | Ensembl ].		VAR_014644
	Natural variant	386	1	V → A in CMO-2 deficiency; small but consistent reduction in the production of 18-hydroxycorticosterone. Ref.6 Ref.7 Ref.12 Ref.14 Ref.16 Corresponds to variant rs4541 [ dbSNP | Ensembl ].		VAR_001269
	Natural variant	403	1	V → E. Corresponds to variant rs5315 [ dbSNP | Ensembl ].		VAR_014645
	Natural variant	435	1	G → S. Ref.14 Ref.16 Corresponds to variant rs4545 [ dbSNP | Ensembl ].		VAR_014156
	Natural variant	461	1	L → P in CMO-1 deficiency; abolishes the 18-hydroxylase activity required for conversion of 11-deoxycorticosterone to aldosterone. Ref.10		VAR_018472
	Natural variant	487	1	F → V. Corresponds to variant rs5317 [ dbSNP | Ensembl ].		VAR_014646
	Natural variant	498	1	T → A in CMO-2 deficiency. Ref.18		VAR_018473
Experimental info
	Sequence conflict	17	1	S → C in AAA35741. Ref.1
	Sequence conflict	55	1	I → M in AAA35741. Ref.1
	Sequence conflict	119	1	Y → I in AAA35741. Ref.1
	Sequence conflict	249	1	S → R in CAA38539. Ref.2
	Sequence conflict	342	1	Q → K in AAA35741. Ref.1
	Sequence conflict	438	1	F → L in AAA35741. Ref.1
	Sequence conflict	470	1	H → R in AAA35741. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P19099 [UniParc]. Last modified July 15, 1998. Version 3. Checksum: 42BA671704CEE35D	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

References

	« Hide 'large scale' referencesShow 'large scale' 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]	NHLBI resequencing and genotyping service (RS&G) Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	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].
[6]	"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.
[7]	"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.
[8]	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)
[9]	"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.
[10]	"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.
[11]	"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.
[12]	"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.
[13]	"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.
[14]	"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.
[15]	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)
[16]	"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.
[17]	"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.
[18]	"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.

Web resources

GeneReviews

Wikipedia

CYP11B2 entry

Cross-references

Sequence databases
EMBL GenBank DDBJ	M32881, M32864, M32880 Genomic DNA. Translation: AAA35741.1. X54741 mRNA. Translation: CAA38539.1. D13752 Genomic DNA. Translation: BAA02899.1. EU326306 Genomic DNA. Translation: ACA05912.1. CH471162 Genomic DNA. Translation: EAW82292.1.
IPI	IPI00290116.
PIR	B34181.
RefSeq	NP_000489.3. NM_000498.3.
UniGene	Hs.632054.
3D structure databases
ProteinModelPortal	P19099.
SMR	P19099. Positions 34-503.
ModBase	Search...
Protein-protein interaction databases
STRING	P19099.
Polymorphism databases
DMDM	3041666.
Proteomic databases
PRIDE	P19099.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000323110; ENSP00000325822; ENSG00000179142.
GeneID	1585.
KEGG	hsa:1585.
UCSC	uc003yxk.1. human.
Organism-specific databases
CTD	1585.
GeneCards	GC08M143988.
H-InvDB	HIX0034383.
HGNC	HGNC:2592. CYP11B2.
MIM	103900. phenotype. 124080. gene. 203400. phenotype. 610600. phenotype.
neXtProt	NX_P19099.
Orphanet	403. Familial hyperaldosteronism type 1. 99763. Familial hyperreninemic hypoaldosteronism type 1.
PharmGKB	PA134.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG05378.
HOGENOM	HBG444565.
HOVERGEN	HBG051098.
InParanoid	P19099.
OMA	EHLHLEM.
OrthoDB	EOG4B2SWV.
PhylomeDB	P19099.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism. REACT_15493. Steroid hormones. REACT_22258. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	P19099.
Bgee	P19099.
CleanEx	HS_CYP11B2.
Genevestigator	P19099.
GermOnline	ENSG00000179142. Homo sapiens.
Family and domain databases
InterPro	IPR001128. Cyt_P450. IPR017972. Cyt_P450_CS. IPR002399. Cyt_P450_mitochondrial. [Graphical view]
Gene3D	G3DSA:1.10.630.10. Cyt_P450. 1 hit.
KO	K07433.
Pfam	PF00067. p450. 1 hit. [Graphical view]
PRINTS	PR00408. MITP450. PR00385. P450.
SUPFAM	SSF48264. Cytochrome_P450. 1 hit.
PROSITE	PS00086. CYTOCHROME_P450. 1 hit. [Graphical view]
ProtoNet	Search...
Other
DrugBank	DB00796. Candesartan. DB01011. Metyrapone.
NextBio	6515.
SOURCE	Search...

Entry information

Entry name

C11B2_HUMAN

Accession

Primary (citable) accession number: P19099
Secondary accession number(s): B0ZBE4, Q16726

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	July 15, 1998
Last modified:	January 25, 2012
This is version 136 of the entry and version 3 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.