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 |
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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 |
| ||
| 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 | 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 | |
| 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. |
Ontologies
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: dbSNP rs6438. Ref.12 | VAR_014151 | |||||
| Natural variant | 30 | 1 | 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 | 1 | N → NRL in CMO-1 deficiency; the enzyme is inactive. | VAR_018470 | |||||
| Natural variant | 173 | 1 | K → R: dbSNP rs4539. Ref.12 Ref.11 Ref.14 | 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. | VAR_001267 | |||||
| Natural variant | 185 | 1 | T → I in CMO-2 deficiency. | VAR_018471 | |||||
| Natural variant | 198 | 1 | E → D in CMO-2 deficiency. | VAR_001268 | |||||
| Natural variant | 222 | 1 | N → T: dbSNP rs5308. | VAR_014643 | |||||
| Natural variant | 248 | 1 | I → T: dbSNP rs4547. Ref.12 Ref.14 | VAR_014153 | |||||
| Natural variant | 281 | 1 | N → S: dbSNP rs4537. Ref.12 Ref.14 | VAR_014154 | |||||
| Natural variant | 339 | 1 | I → T: dbSNP rs4544. Ref.12 Ref.14 | VAR_014155 | |||||
| Natural variant | 383 | 1 | E → V: dbSNP rs5312. | VAR_014644 | |||||
| Natural variant | 386 | 1 | V → A in CMO-2 deficiency; small but consistent reduction in the production of 18-hydroxycorticosterone. dbSNP rs4541. | VAR_001269 | |||||
| Natural variant | 403 | 1 | V → E: dbSNP rs5315. | VAR_014645 | |||||
| Natural variant | 435 | 1 | G → S: dbSNP rs4545. Ref.12 Ref.14 | 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. | VAR_018472 | |||||
| Natural variant | 487 | 1 | F → V: dbSNP rs5317. | VAR_014646 | |||||
| Natural variant | 498 | 1 | T → A in CMO-2 deficiency. | 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
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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. |
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... |
Entry information
| Entry name | C11B2_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P19099 Secondary accession number(s): Q16726 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
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 |

Clusters with


