ID C11B2_HUMAN Reviewed; 503 AA. AC P19099; B0ZBE4; Q16726; DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot. DT 15-JUL-1998, sequence version 3. DT 27-MAR-2024, entry version 226. DE RecName: Full=Cytochrome P450 11B2, mitochondrial; DE AltName: Full=Aldosterone synthase {ECO:0000303|PubMed:9814506}; DE Short=ALDOS; DE AltName: Full=Aldosterone-synthesizing enzyme; DE AltName: Full=CYPXIB2; DE AltName: Full=Corticosterone 18-monooxygenase, CYP11B2; DE EC=1.14.15.5 {ECO:0000269|PubMed:11856349, ECO:0000269|PubMed:15356073, ECO:0000269|PubMed:1594605, ECO:0000269|PubMed:23322723, ECO:0000269|PubMed:9814506}; DE AltName: Full=Cytochrome P-450Aldo; DE AltName: Full=Cytochrome P-450C18; DE AltName: Full=Steroid 11-beta-hydroxylase, CYP11B2 {ECO:0000303|PubMed:2592361}; DE EC=1.14.15.4 {ECO:0000269|PubMed:11856349, ECO:0000269|PubMed:12530636, ECO:0000269|PubMed:1518866, ECO:0000269|PubMed:1775135, ECO:0000269|PubMed:23322723}; DE AltName: Full=Steroid 18-hydroxylase {ECO:0000303|PubMed:9177280}; DE Flags: Precursor; GN Name=CYP11B2 {ECO:0000303|PubMed:1346492, ECO:0000312|HGNC:HGNC:2592}; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2592361; DOI=10.1016/s0021-9258(19)30030-4; RA Mornet E., Dupont J., Vitek A., White P.C.; RT "Characterization of two genes encoding human steroid 11 beta-hydroxylase RT (P-450(11) beta)."; RL J. Biol. Chem. 264:20961-20967(1989). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Adrenal gland; RX PubMed=2256920; DOI=10.1016/s0006-291x(05)81058-7; RA Kawamoto T., Mitsuuchi Y., Ohnishi T., Ichikawa Y., Yokoyama Y., RA Sumimoto H., Toda K., Miyahara K., Kuribayashi I., Nakao K., Hosoda K., RA Yamamoto Y., Imura H., Shizuta Y.; RT "Cloning and expression of a cDNA for human cytochrome P-450aldo as related RT to primary aldosteronism."; RL Biochem. Biophys. Res. Commun. 173:309-316(1990). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC TISSUE=Blood; RA Kawamoto T., Miyahara K., Mitsuuchi Y., Ulick S., Shizuta Y.; RL Submitted (JUN-1994) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RG NHLBI resequencing and genotyping service (RS&G); RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP MISCELLANEOUS. RX PubMed=2040591; DOI=10.1016/s0021-9258(18)99077-0; RA Ogishima T., Shibata H., Shimada H., Mitani F., Suzuki H., Saruta T., RA Ishimura Y.; RT "Aldosterone synthase cytochrome P-450 expressed in the adrenals of RT patients with primary aldosteronism."; RL J. Biol. Chem. 266:10731-10734(1991). RN [7] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=1775135; DOI=10.1210/mend-5-10-1513; RA Curnow K.M., Tusie-Luna M.T., Pascoe L., Natarajan R., Gu J.L., RA Nadler J.L., White P.C.; RT "The product of the CYP11B2 gene is required for aldosterone biosynthesis RT in the human adrenal cortex."; RL Mol. Endocrinol. 5:1513-1522(1991). RN [8] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=1518866; DOI=10.1073/pnas.89.17.8327; RA Pascoe L., Curnow K.M., Slutsker L., Connell J.M., Speiser P.W., New M.I., RA White P.C.; RT "Glucocorticoid-suppressible hyperaldosteronism results from hybrid genes RT created by unequal crossovers between CYP11B1 and CYP11B2."; RL Proc. Natl. Acad. Sci. U.S.A. 89:8327-8331(1992). RN [9] RP INDUCTION. RX PubMed=9139807; DOI=10.1210/mend.11.5.9920; RA Clyne C.D., Zhang Y., Slutsker L., Mathis J.M., White P.C., Rainey W.E.; RT "Angiotensin II and potassium regulate human CYP11B2 transcription through RT common cis-elements."; RL Mol. Endocrinol. 11:638-649(1997). RN [10] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=9814482; DOI=10.1210/jcem.83.11.5237; RA Mulatero P., Curnow K.M., Aupetit-Faisant B., Foekling M., RA Gomez-Sanchez C., Veglio F., Jeunemaitre X., Corvol P., Pascoe L.; RT "Recombinant CYP11B genes encode enzymes that can catalyze conversion of RT 11-deoxycortisol to cortisol, 18-hydroxycortisol, and 18-oxocortisol."; RL J. Clin. Endocrinol. Metab. 83:3996-4001(1998). RN [11] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=12530636; DOI=10.1081/erc-120016808; RA Bureik M., Zeeh A., Bernhardt R.; RT "Modulation of steroid hydroxylase activity in stably transfected RT V79MZh11B1 and V79MZh11B2 cells by PKC and PKD inhibitors."; RL Endocr. Res. 28:351-355(2002). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND MUTAGENESIS OF ILE-112; ASP-147 RP AND LYS-152. RX PubMed=11856349; DOI=10.1046/j.1432-1033.2002.02729.x; RA Bechtel S., Belkina N., Bernhardt R.; RT "The effect of amino-acid substitutions I112P, D147E and K152N in CYP11B2 RT on the catalytic activities of the enzyme."; RL Eur. J. Biochem. 269:1118-1127(2002). RN [13] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=15356073; DOI=10.1210/jc.2004-0379; RA Freel E.M., Shakerdi L.A., Friel E.C., Wallace A.M., Davies E., Fraser R., RA Connell J.M.; RT "Studies on the origin of circulating 18-hydroxycortisol and 18-oxocortisol RT in normal human subjects."; RL J. Clin. Endocrinol. Metab. 89:4628-4633(2004). RN [14] RP TISSUE SPECIFICITY. RX PubMed=20200334; DOI=10.1210/jc.2009-2010; RA Nishimoto K., Nakagawa K., Li D., Kosaka T., Oya M., Mikami S., Shibata H., RA Itoh H., Mitani F., Yamazaki T., Ogishima T., Suematsu M., Mukai K.; RT "Adrenocortical zonation in humans under normal and pathological RT conditions."; RL J. Clin. Endocrinol. Metab. 95:2296-2305(2010). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=22446688; DOI=10.1016/j.jsbmb.2012.03.002; RA Hobler A., Kagawa N., Hutter M.C., Hartmann M.F., Wudy S.A., Hannemann F., RA Bernhardt R.; RT "Human aldosterone synthase: recombinant expression in E. coli and RT purification enables a detailed biochemical analysis of the protein on the RT molecular level."; RL J. Steroid Biochem. Mol. Biol. 132:57-65(2012). RN [16] RP X-RAY CRYSTALLOGRAPHY (2.49 ANGSTROMS) OF 34-503 IN COMPLEXES WITH HEME; RP DESOXYCORTICOSTERONE AND SYNTHETIC INHIBITOR FADROZOLE, CATALYTIC ACTIVITY, RP COFACTOR, FUNCTION, AND PATHWAY. RX PubMed=23322723; DOI=10.1210/me.2012-1287; RA Strushkevich N., Gilep A.A., Shen L., Arrowsmith C.H., Edwards A.M., RA Usanov S.A., Park H.W.; RT "Structural insights into aldosterone synthase substrate specificity and RT targeted inhibition."; RL Mol. Endocrinol. 27:315-324(2013). RN [17] RP VARIANTS CMO-2 DEFICIENCY TRP-181 AND ALA-386, CATALYTIC ACTIVITY, RP FUNCTION, AND PATHWAY. RX PubMed=1594605; DOI=10.1073/pnas.89.11.4996; RA Pascoe L., Curnow K.M., Slutsker L., Roesler A., White P.C.; RT "Mutations in the human CYP11B2 (aldosterone synthase) gene causing RT corticosterone methyloxidase II deficiency."; RL Proc. Natl. Acad. Sci. U.S.A. 89:4996-5000(1992). RN [18] RP VARIANTS CMO-2 DEFICIENCY TRP-181 AND ALA-386. RX PubMed=1346492; DOI=10.1016/0006-291x(92)91827-d; RA Mitsuuchi Y., Kawamoto T., Naiki Y., Miyahara K., Toda K., Kuribayashi I., RA Orii T., Yasuda K., Miura K., Nakao K., Imura H., Ulick S., Shizuta Y.; RT "Congenitally defective aldosterone biosynthesis in humans: the involvement RT of point mutations of the P-450C18 gene (CYP11B2) in CMO II deficient RT patients."; RL Biochem. Biophys. Res. Commun. 182:974-979(1992). RN [19] RP ERRATUM OF PUBMED:1346492. RA Mitsuuchi Y., Kawamoto T., Naiki Y., Miyahara K., Toda K., Kuribayashi I., RA Orii T., Yasuda K., Miura K., Nakao K., Imura H., Ulick S., Shizuta Y.; RL Biochem. Biophys. Res. Commun. 184:1529-1530(1992). RN [20] RP INVOLVEMENT IN CMO-1 DEFICIENCY. RX PubMed=8439335; DOI=10.1006/bbrc.1993.1128; RA Mitsuuchi Y., Kawamoto T., Miyahara K., Ulick S., Morton D.H., Naiki Y., RA Kuribayashi I., Toda K., Hara T., Orii T., Yasuda K., Miura K., RA Yamamoto Y., Imura H., Shizuta Y.; RT "Congenitally defective aldosterone biosynthesis in humans: inactivation of RT the P-450(C18) gene (CYP11B2) due to nucleotide deletion in CMO I deficient RT patients."; RL Biochem. Biophys. Res. Commun. 190:864-869(1993). RN [21] RP VARIANT CMO-1 DEFICIENCY PRO-461. RX PubMed=9177280; DOI=10.1006/bbrc.1997.6651; RA Nomoto S., Massa G., Mitani F., Ishimura Y., Miyahara K., Toda K., RA Nagano I., Yamashiro T., Ogoshi S., Fukata J., Onishi S., Hashimoto K., RA Doi Y., Imura H., Shizuta Y.; RT "CMO I deficiency caused by a point mutation in exon 8 of the human CYP11B2 RT gene encoding steroid 18-hydroxylase (P450C18)."; RL Biochem. Biophys. Res. Commun. 234:382-385(1997). RN [22] RP VARIANT CMO-2 DEFICIENCY ILE-185. RX PubMed=9625333; DOI=10.1007/s004310050833; RA Peter M., Buenger K., Solyom J., Sippell W.G.; RT "Mutation THR-185 ILE is associated with corticosterone methyl oxidase RT deficiency type II."; RL Eur. J. Pediatr. 157:378-381(1998). RN [23] RP VARIANTS CMO-2 DEFICIENCY ASP-198 AND ALA-386, FUNCTION, CATALYTIC RP ACTIVITY, AND PATHWAY. RX PubMed=9814506; DOI=10.1210/jcem.83.11.5258; RA Portrat-Doyen S., Tourniaire J., Richard O., Mulatero P., RA Aupetit-Faisant B., Curnow K.M., Pascoe L., Morel Y.; RT "Isolated aldosterone synthase deficiency caused by simultaneous E198D and RT V386A mutations in the CYP11B2 gene."; RL J. Clin. Endocrinol. Metab. 83:4156-4161(1998). RN [24] RP VARIANT ARG-173. RX PubMed=9931115; DOI=10.1161/01.hyp.33.1.266; RA Tamaki S., Iwai N., Tsujita Y., Kinoshita M.; RT "Genetic polymorphism of CYP11B2 gene and hypertension in Japanese."; RL Hypertension 33:266-270(1999). RN [25] RP VARIANTS THR-29; GLN-30; ARG-173; THR-248; SER-281; THR-339; ALA-386 AND RP SER-435. RX PubMed=10391209; DOI=10.1038/10290; RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RT "Characterization of single-nucleotide polymorphisms in coding regions of RT human genes."; RL Nat. Genet. 22:231-238(1999). RN [26] RP ERRATUM OF PUBMED:10391209. RA Cargill M., Altshuler D., Ireland J., Sklar P., Ardlie K., Patil N., RA Shaw N., Lane C.R., Lim E.P., Kalyanaraman N., Nemesh J., Ziaugra L., RA Friedland L., Rolfe A., Warrington J., Lipshutz R., Daley G.Q., RA Lander E.S.; RL Nat. Genet. 23:373-373(1999). RN [27] RP VARIANTS ARG-173; THR-248; SER-281; THR-339; ALA-386 AND SER-435. RX PubMed=10391210; DOI=10.1038/10297; RA Halushka M.K., Fan J.-B., Bentley K., Hsie L., Shen N., Weder A., RA Cooper R., Lipshutz R., Chakravarti A.; RT "Patterns of single-nucleotide polymorphisms in candidate genes for blood- RT pressure homeostasis."; RL Nat. Genet. 22:239-247(1999). RN [28] RP VARIANT CMO-1 DEFICIENCY ARG-LEU-140 INS. RX PubMed=11238478; DOI=10.1210/jcem.86.3.7326; RA Kayes-Wandover K.M., Schindler R.E.L., Taylor H.C., White P.C.; RT "Type 1 aldosterone synthase deficiency presenting in a middle-aged man."; RL J. Clin. Endocrinol. Metab. 86:1008-1012(2001). RN [29] RP VARIANTS CMO-2 DEFICIENCY ILE-185 AND ALA-498. RX PubMed=12788848; DOI=10.1210/jc.2003-030353; RA Dunlop F.M., Crock P.A., Montalto J., Funder J.W., Curnow K.M.; RT "A compound heterozygote case of type II aldosterone synthase deficiency."; RL J. Clin. Endocrinol. Metab. 88:2518-2526(2003). CC -!- FUNCTION: A cytochrome P450 monooxygenase that catalyzes the CC biosynthesis of aldosterone, the main mineralocorticoid in the human CC body responsible for salt and water homeostasis, thus involved in blood CC pressure regulation, arterial hypertension, and the development of CC heart failure (PubMed:1775135, PubMed:1518866, PubMed:9814482, CC PubMed:15356073, PubMed:12530636, PubMed:22446688, PubMed:11856349, CC PubMed:23322723, PubMed:1594605, PubMed:9814506). Catalyzes three CC sequential oxidative reactions of 11-deoxycorticosterone (21- CC hydroxyprogesterone), namely 11-beta hydroxylation, followed by two CC successive oxidations at C18 yielding 18-hydroxy and then 18-oxo CC intermediates (that would not leave the enzyme active site during the CC consecutive hydroxylation reactions), ending with the formation of CC aldosterone (PubMed:1775135, PubMed:1518866, PubMed:12530636, CC PubMed:22446688, PubMed:11856349, PubMed:23322723, PubMed:1594605, CC PubMed:9814506). Can also produce 18-hydroxycortisol and 18- CC oxocortisol, derived from successive oxidations of cortisol at C18, CC normally found at very low levels, but significantly increased in CC primary aldosteronism, the most common form of secondary hypertension CC (PubMed:15356073, PubMed:9814482). Mechanistically, uses molecular CC oxygen inserting one oxygen atom into a substrate and reducing the CC second into a water molecule. Two electrons are provided by NADPH via a CC two-protein mitochondrial transfer system comprising flavoprotein FDXR CC (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1 CC or FDX2 (adrenodoxin/ferredoxin) (PubMed:11856349, PubMed:1594605, CC PubMed:23322723, PubMed:9814506). Could also be involved in the CC androgen metabolic pathway (Probable). {ECO:0000269|PubMed:11856349, CC ECO:0000269|PubMed:12530636, ECO:0000269|PubMed:1518866, CC ECO:0000269|PubMed:15356073, ECO:0000269|PubMed:1594605, CC ECO:0000269|PubMed:1775135, ECO:0000269|PubMed:22446688, CC ECO:0000269|PubMed:23322723, ECO:0000269|PubMed:9814482, CC ECO:0000269|PubMed:9814506, ECO:0000305|PubMed:23322723}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a steroid + 2 H(+) + O2 + 2 reduced [adrenodoxin] = an 11beta- CC hydroxysteroid + H2O + 2 oxidized [adrenodoxin]; CC Xref=Rhea:RHEA:15629, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:35341, CC ChEBI:CHEBI:35346; EC=1.14.15.4; CC Evidence={ECO:0000269|PubMed:11856349, ECO:0000269|PubMed:12530636, CC ECO:0000269|PubMed:1518866, ECO:0000269|PubMed:1775135, CC ECO:0000269|PubMed:22446688, ECO:0000269|PubMed:23322723}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15630; CC Evidence={ECO:0000269|PubMed:1518866, ECO:0000269|PubMed:1775135, CC ECO:0000305|PubMed:11856349, ECO:0000305|PubMed:12530636, CC ECO:0000305|PubMed:22446688, ECO:0000305|PubMed:23322723}; CC -!- CATALYTIC ACTIVITY: CC Reaction=21-hydroxyprogesterone + 2 H(+) + O2 + 2 reduced [adrenodoxin] CC = corticosterone + H2O + 2 oxidized [adrenodoxin]; CC Xref=Rhea:RHEA:46104, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16827, ChEBI:CHEBI:16973, ChEBI:CHEBI:33737, CC ChEBI:CHEBI:33738; Evidence={ECO:0000269|PubMed:11856349, CC ECO:0000269|PubMed:12530636, ECO:0000269|PubMed:1518866, CC ECO:0000269|PubMed:1594605, ECO:0000269|PubMed:1775135, CC ECO:0000269|PubMed:22446688, ECO:0000269|PubMed:23322723, CC ECO:0000269|PubMed:9814506}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46105; CC Evidence={ECO:0000269|PubMed:1518866, ECO:0000269|PubMed:1775135, CC ECO:0000305|PubMed:11856349, ECO:0000305|PubMed:12530636, CC ECO:0000305|PubMed:22446688, ECO:0000305|PubMed:23322723}; CC -!- CATALYTIC ACTIVITY: CC Reaction=corticosterone + 2 H(+) + O2 + 2 reduced [adrenodoxin] = 18- CC hydroxycorticosterone + H2O + 2 oxidized [adrenodoxin]; CC Xref=Rhea:RHEA:11872, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16485, ChEBI:CHEBI:16827, ChEBI:CHEBI:33737, CC ChEBI:CHEBI:33738; EC=1.14.15.5; CC Evidence={ECO:0000269|PubMed:11856349, ECO:0000269|PubMed:15356073, CC ECO:0000269|PubMed:1594605, ECO:0000269|PubMed:22446688, CC ECO:0000269|PubMed:23322723, ECO:0000269|PubMed:9814506, CC ECO:0000305|PubMed:12530636, ECO:0000305|PubMed:1518866, CC ECO:0000305|PubMed:1775135}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11873; CC Evidence={ECO:0000305|PubMed:11856349, ECO:0000305|PubMed:12530636, CC ECO:0000305|PubMed:1518866, ECO:0000305|PubMed:15356073, CC ECO:0000305|PubMed:1775135, ECO:0000305|PubMed:22446688, CC ECO:0000305|PubMed:23322723}; CC -!- CATALYTIC ACTIVITY: CC Reaction=18-hydroxycorticosterone + 2 H(+) + O2 + 2 reduced CC [adrenodoxin] = aldosterone + 2 H2O + 2 oxidized [adrenodoxin]; CC Xref=Rhea:RHEA:50792, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16485, ChEBI:CHEBI:27584, ChEBI:CHEBI:33737, CC ChEBI:CHEBI:33738; Evidence={ECO:0000269|PubMed:11856349, CC ECO:0000269|PubMed:15356073, ECO:0000269|PubMed:1594605, CC ECO:0000269|PubMed:9814506, ECO:0000305|PubMed:22446688}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:50793; CC Evidence={ECO:0000305|PubMed:11856349, ECO:0000305|PubMed:12530636, CC ECO:0000305|PubMed:1518866, ECO:0000305|PubMed:15356073, CC ECO:0000305|PubMed:1775135, ECO:0000305|PubMed:22446688}; CC -!- CATALYTIC ACTIVITY: CC Reaction=11-deoxycortisol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = CC cortisol + H2O + 2 oxidized [adrenodoxin]; Xref=Rhea:RHEA:46100, CC Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:17650, CC ChEBI:CHEBI:28324, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738; CC Evidence={ECO:0000269|PubMed:11856349, ECO:0000269|PubMed:12530636, CC ECO:0000269|PubMed:1775135, ECO:0000269|PubMed:23322723}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46101; CC Evidence={ECO:0000269|PubMed:1775135, ECO:0000305|PubMed:12530636, CC ECO:0000305|PubMed:23322723}; CC -!- CATALYTIC ACTIVITY: CC Reaction=21-hydroxyprogesterone + 2 H(+) + O2 + 2 reduced [adrenodoxin] CC = 18-hydroxy-11-deoxycorticosterone + H2O + 2 oxidized [adrenodoxin]; CC Xref=Rhea:RHEA:76151, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16973, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, CC ChEBI:CHEBI:195166; Evidence={ECO:0000250|UniProtKB:P30099}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76152; CC Evidence={ECO:0000250|UniProtKB:P30099}; CC -!- CATALYTIC ACTIVITY: CC Reaction=cortisol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = 18- CC hydroxycortisol + H2O + 2 oxidized [adrenodoxin]; CC Xref=Rhea:RHEA:76019, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:17650, ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, CC ChEBI:CHEBI:89455; Evidence={ECO:0000269|PubMed:15356073, CC ECO:0000269|PubMed:9814482}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76020; CC Evidence={ECO:0000305|PubMed:15356073, ECO:0000305|PubMed:9814482}; CC -!- CATALYTIC ACTIVITY: CC Reaction=18-hydroxycortisol + 2 H(+) + O2 + 2 reduced [adrenodoxin] = CC 18-oxocortisol + 2 H2O + 2 oxidized [adrenodoxin]; CC Xref=Rhea:RHEA:76023, Rhea:RHEA-COMP:9998, Rhea:RHEA-COMP:9999, CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:33737, ChEBI:CHEBI:33738, ChEBI:CHEBI:89213, CC ChEBI:CHEBI:89455; Evidence={ECO:0000305|PubMed:15356073, CC ECO:0000305|PubMed:9814482}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:76024; CC Evidence={ECO:0000305|PubMed:15356073, ECO:0000305|PubMed:9814482}; CC -!- COFACTOR: CC Name=heme; Xref=ChEBI:CHEBI:30413; CC Evidence={ECO:0000269|PubMed:23322723}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=2.6 uM for cortisol {ECO:0000269|PubMed:15356073}; CC KM=106 uM for 11-deoxycorticosterone {ECO:0000269|PubMed:22446688}; CC Vmax=238 nmol/min/nmol enzyme with 11-deoxycorticosterone CC {ECO:0000269|PubMed:22446688}; CC -!- PATHWAY: Steroid biosynthesis. {ECO:0000269|PubMed:11856349, CC ECO:0000269|PubMed:1594605, ECO:0000269|PubMed:23322723, CC ECO:0000269|PubMed:9814506}. CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane CC {ECO:0000250|UniProtKB:P14137}; Peripheral membrane protein CC {ECO:0000250|UniProtKB:P14137}. CC -!- TISSUE SPECIFICITY: Expressed sporadically in the zona glomerulosa (zG) CC of the adrenal cortex (conventional zonation), as well as in CC aldosterone-producing cell clusters (APCCs) composed of morphological CC zG cells in contact with the capsule (variegated zonation). CC {ECO:0000269|PubMed:20200334}. CC -!- INDUCTION: Expression is induced by angiotensin II, potassium (K+), and CC also by cAMP. {ECO:0000269|PubMed:9139807}. CC -!- DISEASE: Corticosterone methyloxidase 1 deficiency (CMO-1 deficiency) CC [MIM:203400]: Autosomal recessive disorder of aldosterone biosynthesis. CC There are two biochemically different forms of selective aldosterone CC deficiency be termed corticosterone methyloxidase (CMO) deficiency type CC 1 and type 2. In CMO-1 deficiency, aldosterone is undetectable in CC plasma, while its immediate precursor, 18-hydroxycorticosterone, is low CC or normal. {ECO:0000269|PubMed:11238478, ECO:0000269|PubMed:8439335, CC ECO:0000269|PubMed:9177280}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Corticosterone methyloxidase 2 deficiency (CMO-2 deficiency) CC [MIM:610600]: Autosomal recessive disorder of aldosterone biosynthesis. CC In CMO-2 deficiency, aldosterone can be low or normal, but at the CC expense of increased secretion of 18-hydroxycorticosterone. CC Consequently, patients have a greatly increased ratio of 18- CC hydroxycorticosterone to aldosterone and a low ratio of corticosterone CC to 18-hydroxycorticosterone in serum. {ECO:0000269|PubMed:12788848, CC ECO:0000269|PubMed:1346492, ECO:0000269|PubMed:1594605, CC ECO:0000269|PubMed:9625333, ECO:0000269|PubMed:9814506}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- MISCELLANEOUS: Expressed in aldosterone-secreting tumors and in adrenal CC glands of patients with idiopathic hyperaldosteronism. CC {ECO:0000269|PubMed:2040591}. CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=CYP11B2 entry; CC URL="https://en.wikipedia.org/wiki/CYP11B2"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M32881; AAA35741.1; -; Genomic_DNA. DR EMBL; M32864; AAA35741.1; JOINED; Genomic_DNA. DR EMBL; M32880; AAA35741.1; JOINED; Genomic_DNA. DR EMBL; X54741; CAA38539.1; -; mRNA. DR EMBL; D13752; BAA02899.1; -; Genomic_DNA. DR EMBL; EU326306; ACA05912.1; -; Genomic_DNA. DR EMBL; CH471162; EAW82292.1; -; Genomic_DNA. DR CCDS; CCDS6393.1; -. DR PIR; B34181; B34181. DR RefSeq; NP_000489.3; NM_000498.3. DR PDB; 4DVQ; X-ray; 2.49 A; A/B/C/D/E/F/G/H/I/J/K/L=34-503. DR PDB; 4FDH; X-ray; 2.71 A; A/B/C/D/E/F/G/H/I/J/K/L=34-503. DR PDB; 4ZGX; X-ray; 3.20 A; A/B/C/D/E/F/G/H/I/J/K/L=28-503. DR PDB; 6XZ8; X-ray; 3.00 A; A/B/C=28-503. DR PDB; 6XZ9; X-ray; 2.77 A; A/B/C=28-503. DR PDB; 7M8I; X-ray; 2.94 A; A/B/C=31-503. DR PDB; 7M8V; X-ray; 3.08 A; A/B/C/D/E/F/G/H/I/J/K/L=31-503. DR PDBsum; 4DVQ; -. DR PDBsum; 4FDH; -. DR PDBsum; 4ZGX; -. DR PDBsum; 6XZ8; -. DR PDBsum; 6XZ9; -. DR PDBsum; 7M8I; -. DR PDBsum; 7M8V; -. DR AlphaFoldDB; P19099; -. DR SMR; P19099; -. DR BioGRID; 107957; 7. DR STRING; 9606.ENSP00000325822; -. DR BindingDB; P19099; -. DR ChEMBL; CHEMBL2722; -. DR DrugBank; DB04630; Aldosterone. DR DrugBank; DB00700; Eplerenone. DR DrugBank; DB00292; Etomidate. DR DrugBank; DB00741; Hydrocortisone. DR DrugBank; DB14539; Hydrocortisone acetate. DR DrugBank; DB14540; Hydrocortisone butyrate. DR DrugBank; DB14543; Hydrocortisone probutate. DR DrugBank; DB14545; Hydrocortisone succinate. DR DrugBank; DB14544; Hydrocortisone valerate. DR DrugBank; DB05667; Levoketoconazole. DR DrugBank; DB01011; Metyrapone. DR DrugBank; DB01388; Mibefradil. DR DrugBank; DB11837; Osilodrostat. DR DrugBank; DB00421; Spironolactone. DR DrugBank; DB06281; Torcetrapib. DR DrugCentral; P19099; -. DR GuidetoPHARMACOLOGY; 1360; -. DR SwissLipids; SLP:000001198; -. DR iPTMnet; P19099; -. DR PhosphoSitePlus; P19099; -. DR BioMuta; CYP11B2; -. DR DMDM; 3041666; -. DR MassIVE; P19099; -. DR PaxDb; 9606-ENSP00000325822; -. DR PeptideAtlas; P19099; -. DR ProteomicsDB; 53632; -. DR Antibodypedia; 14554; 280 antibodies from 33 providers. DR DNASU; 1585; -. DR Ensembl; ENST00000323110.2; ENSP00000325822.2; ENSG00000179142.2. DR GeneID; 1585; -. DR KEGG; hsa:1585; -. DR MANE-Select; ENST00000323110.2; ENSP00000325822.2; NM_000498.3; NP_000489.3. DR UCSC; uc003yxk.1; human. DR AGR; HGNC:2592; -. DR CTD; 1585; -. DR DisGeNET; 1585; -. DR GeneCards; CYP11B2; -. DR HGNC; HGNC:2592; CYP11B2. DR HPA; ENSG00000179142; Tissue enriched (adrenal). DR MalaCards; CYP11B2; -. DR MIM; 124080; gene. DR MIM; 203400; phenotype. DR MIM; 610600; phenotype. DR neXtProt; NX_P19099; -. DR OpenTargets; ENSG00000179142; -. DR Orphanet; 556030; Early-onset familial hypoaldosteronism. DR Orphanet; 403; Familial hyperaldosteronism type I. DR PharmGKB; PA134; -. DR VEuPathDB; HostDB:ENSG00000179142; -. DR eggNOG; KOG0159; Eukaryota. DR GeneTree; ENSGT00940000163354; -. DR HOGENOM; CLU_001570_28_4_1; -. DR InParanoid; P19099; -. DR OMA; QESMATE; -. DR OrthoDB; 2658719at2759; -. DR PhylomeDB; P19099; -. DR TreeFam; TF105094; -. DR BioCyc; MetaCyc:HS11355-MONOMER; -. DR BRENDA; 1.14.15.4; 2681. DR BRENDA; 1.14.15.5; 2681. DR PathwayCommons; P19099; -. DR Reactome; R-HSA-193993; Mineralocorticoid biosynthesis. DR Reactome; R-HSA-194002; Glucocorticoid biosynthesis. DR Reactome; R-HSA-211976; Endogenous sterols. DR Reactome; R-HSA-5579009; Defective CYP11B2 causes CMO-1 deficiency. DR SignaLink; P19099; -. DR SIGNOR; P19099; -. DR BioGRID-ORCS; 1585; 12 hits in 1146 CRISPR screens. DR GeneWiki; Aldosterone_synthase; -. DR GenomeRNAi; 1585; -. DR Pharos; P19099; Tchem. DR PRO; PR:P19099; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; P19099; Protein. DR Bgee; ENSG00000179142; Expressed in right adrenal gland cortex and 26 other cell types or tissues. DR GO; GO:0005743; C:mitochondrial inner membrane; IBA:GO_Central. DR GO; GO:0005739; C:mitochondrion; IDA:BHF-UCL. DR GO; GO:0047783; F:corticosterone 18-monooxygenase activity; IBA:GO_Central. DR GO; GO:0020037; F:heme binding; IDA:UniProtKB. DR GO; GO:0005506; F:iron ion binding; IEA:InterPro. DR GO; GO:0004507; F:steroid 11-beta-monooxygenase activity; IDA:UniProtKB. DR GO; GO:0008395; F:steroid hydroxylase activity; TAS:Reactome. DR GO; GO:0032342; P:aldosterone biosynthetic process; IDA:UniProtKB. DR GO; GO:0006700; P:C21-steroid hormone biosynthetic process; IDA:BHF-UCL. DR GO; GO:0032870; P:cellular response to hormone stimulus; IEP:UniProtKB. DR GO; GO:0071375; P:cellular response to peptide hormone stimulus; IBA:GO_Central. DR GO; GO:0035865; P:cellular response to potassium ion; IEP:UniProtKB. DR GO; GO:0008203; P:cholesterol metabolic process; IBA:GO_Central. DR GO; GO:0034651; P:cortisol biosynthetic process; IMP:UniProtKB. DR GO; GO:0034650; P:cortisol metabolic process; IBA:GO_Central. DR GO; GO:0006704; P:glucocorticoid biosynthetic process; IBA:GO_Central. DR GO; GO:0006705; P:mineralocorticoid biosynthetic process; TAS:Reactome. DR GO; GO:0055075; P:potassium ion homeostasis; IMP:BHF-UCL. DR GO; GO:0002017; P:regulation of blood volume by renal aldosterone; IMP:BHF-UCL. DR GO; GO:0003091; P:renal water homeostasis; IC:BHF-UCL. DR GO; GO:0055078; P:sodium ion homeostasis; IMP:BHF-UCL. DR GO; GO:0016125; P:sterol metabolic process; TAS:Reactome. DR CDD; cd20644; CYP11B; 1. DR Gene3D; 1.10.630.10; Cytochrome P450; 1. DR InterPro; IPR001128; Cyt_P450. DR InterPro; IPR017972; Cyt_P450_CS. DR InterPro; IPR002399; Cyt_P450_mitochondrial. DR InterPro; IPR036396; Cyt_P450_sf. DR PANTHER; PTHR24279; -; 1. DR PANTHER; PTHR24279:SF1; CYTOCHROME P450 11B2, MITOCHONDRIAL; 1. DR Pfam; PF00067; p450; 1. DR PRINTS; PR00408; MITP450. DR PRINTS; PR00385; P450. DR SUPFAM; SSF48264; Cytochrome P450; 1. DR PROSITE; PS00086; CYTOCHROME_P450; 1. DR Genevisible; P19099; HS. PE 1: Evidence at protein level; KW 3D-structure; Disease variant; Heme; Iron; Lipid metabolism; Membrane; KW Metal-binding; Mitochondrion; Mitochondrion inner membrane; Monooxygenase; KW Oxidoreductase; Reference proteome; Steroid metabolism; Steroidogenesis; KW Transit peptide. FT TRANSIT 1..24 FT /note="Mitochondrion" FT CHAIN 25..503 FT /note="Cytochrome P450 11B2, mitochondrial" FT /id="PRO_0000003597" FT BINDING 381 FT /ligand="21-hydroxyprogesterone" FT /ligand_id="ChEBI:CHEBI:16973" FT /evidence="ECO:0000269|PubMed:23322723, FT ECO:0007744|PDB:4DVQ" FT BINDING 450 FT /ligand="heme" FT /ligand_id="ChEBI:CHEBI:30413" FT /ligand_part="Fe" FT /ligand_part_id="ChEBI:CHEBI:18248" FT /note="axial binding residue" FT /evidence="ECO:0000269|PubMed:23322723, FT ECO:0007744|PDB:4DVQ, ECO:0007744|PDB:4FDH" FT VARIANT 29 FT /note="A -> T (in dbSNP:rs6438)" FT /evidence="ECO:0000269|PubMed:10391209" FT /id="VAR_014151" FT VARIANT 30 FT /note="R -> Q (in dbSNP:rs6441)" FT /evidence="ECO:0000269|PubMed:10391209" FT /id="VAR_014152" FT VARIANT 140 FT /note="N -> NRL (in CMO-1 deficiency; the enzyme is FT inactive)" FT /id="VAR_018470" FT VARIANT 173 FT /note="K -> R (in dbSNP:rs4539)" FT /evidence="ECO:0000269|PubMed:10391209, FT ECO:0000269|PubMed:10391210, ECO:0000269|PubMed:9931115" FT /id="VAR_001266" FT VARIANT 181 FT /note="R -> W (in CMO-2 deficiency; reduces 18-hydroxylase FT and abolishes 18-oxidase activities; leaves 11 FT beta-hydroxylase activity intact; dbSNP:rs28931609)" FT /evidence="ECO:0000269|PubMed:1346492, FT ECO:0000269|PubMed:1594605" FT /id="VAR_001267" FT VARIANT 185 FT /note="T -> I (in CMO-2 deficiency; dbSNP:rs121912978)" FT /evidence="ECO:0000269|PubMed:12788848, FT ECO:0000269|PubMed:9625333" FT /id="VAR_018471" FT VARIANT 198 FT /note="E -> D (in CMO-2 deficiency; associated in cis with FT A-386; slightly reduced 11-beta-hydroxylase activity, FT greatly decreased 18-hydroxylase activity and absent FT 18-oxidase activity when associated with A-386; FT dbSNP:rs104894072)" FT /evidence="ECO:0000269|PubMed:9814506" FT /id="VAR_001268" FT VARIANT 222 FT /note="N -> T (in dbSNP:rs5308)" FT /id="VAR_014643" FT VARIANT 248 FT /note="I -> T (in dbSNP:rs4547)" FT /evidence="ECO:0000269|PubMed:10391209, FT ECO:0000269|PubMed:10391210" FT /id="VAR_014153" FT VARIANT 281 FT /note="N -> S (in dbSNP:rs4537)" FT /evidence="ECO:0000269|PubMed:10391209, FT ECO:0000269|PubMed:10391210" FT /id="VAR_014154" FT VARIANT 339 FT /note="I -> T (in dbSNP:rs4544)" FT /evidence="ECO:0000269|PubMed:10391209, FT ECO:0000269|PubMed:10391210" FT /id="VAR_014155" FT VARIANT 383 FT /note="E -> V (in dbSNP:rs5312)" FT /id="VAR_014644" FT VARIANT 386 FT /note="V -> A (in CMO-2 deficiency; associated in cis with FT D-198; small but consistent reduction in the production of FT 18-hydroxycorticosterone; slightly reduced FT 11-beta-hydroxylase activity, greatly decreased FT 18-hydroxylase activity and absent 18-oxidase activity when FT associated with D-198; dbSNP:rs61757294)" FT /evidence="ECO:0000269|PubMed:10391209, FT ECO:0000269|PubMed:10391210, ECO:0000269|PubMed:1346492, FT ECO:0000269|PubMed:1594605, ECO:0000269|PubMed:9814506" FT /id="VAR_001269" FT VARIANT 403 FT /note="V -> E (in dbSNP:rs5315)" FT /id="VAR_014645" FT VARIANT 435 FT /note="G -> S (in dbSNP:rs4545)" FT /evidence="ECO:0000269|PubMed:10391209, FT ECO:0000269|PubMed:10391210" FT /id="VAR_014156" FT VARIANT 461 FT /note="L -> P (in CMO-1 deficiency; abolishes the FT 18-hydroxylase activity required for conversion of FT 11-deoxycorticosterone to aldosterone; dbSNP:rs72554627)" FT /evidence="ECO:0000269|PubMed:9177280" FT /id="VAR_018472" FT VARIANT 487 FT /note="F -> V (in dbSNP:rs5317)" FT /id="VAR_014646" FT VARIANT 498 FT /note="T -> A (in CMO-2 deficiency; dbSNP:rs72554626)" FT /evidence="ECO:0000269|PubMed:12788848" FT /id="VAR_018473" FT MUTAGEN 112 FT /note="I->P: Increases 11-beta- and 18-hydroxylase FT activities toward 11-deoxycorticosterone; increases FT 11-beta-hydroxylase activity toward 11-deoxycortisol." FT /evidence="ECO:0000269|PubMed:11856349" FT MUTAGEN 147 FT /note="D->E: Increases 11-beta-hydroxylase activity toward FT 11-deoxycorticosterone and 11-deoxycortisol." FT /evidence="ECO:0000269|PubMed:11856349" FT MUTAGEN 152 FT /note="K->N: No significant effect on hydroxylase FT activities toward 11-deoxycorticosterone and FT 11-deoxycortisol." FT /evidence="ECO:0000269|PubMed:11856349" FT CONFLICT 17 FT /note="S -> C (in Ref. 1; AAA35741)" FT /evidence="ECO:0000305" FT CONFLICT 55 FT /note="I -> M (in Ref. 1; AAA35741)" FT /evidence="ECO:0000305" FT CONFLICT 119 FT /note="Y -> I (in Ref. 1; AAA35741)" FT /evidence="ECO:0000305" FT CONFLICT 249 FT /note="S -> R (in Ref. 2; CAA38539)" FT /evidence="ECO:0000305" FT CONFLICT 342 FT /note="Q -> K (in Ref. 1; AAA35741)" FT /evidence="ECO:0000305" FT CONFLICT 438 FT /note="F -> L (in Ref. 1; AAA35741)" FT /evidence="ECO:0000305" FT CONFLICT 470 FT /note="H -> R (in Ref. 1; AAA35741)" FT /evidence="ECO:0000305" FT HELIX 38..40 FT /evidence="ECO:0007829|PDB:4DVQ" FT HELIX 48..58 FT /evidence="ECO:0007829|PDB:4DVQ" FT HELIX 64..75 FT /evidence="ECO:0007829|PDB:4DVQ" FT STRAND 77..80 FT /evidence="ECO:0007829|PDB:4DVQ" FT STRAND 84..86 FT /evidence="ECO:0007829|PDB:4DVQ" FT STRAND 88..91 FT /evidence="ECO:0007829|PDB:4DVQ" FT HELIX 94..103 FT /evidence="ECO:0007829|PDB:4DVQ" FT HELIX 114..123 FT /evidence="ECO:0007829|PDB:4DVQ" FT HELIX 129..131 FT /evidence="ECO:0007829|PDB:4DVQ" FT HELIX 134..142 FT /evidence="ECO:0007829|PDB:4DVQ" FT HELIX 145..148 FT /evidence="ECO:0007829|PDB:4DVQ" FT HELIX 151..178 FT /evidence="ECO:0007829|PDB:4DVQ" FT STRAND 182..186 FT /evidence="ECO:0007829|PDB:4DVQ" FT HELIX 189..205 FT /evidence="ECO:0007829|PDB:4DVQ" FT STRAND 212..214 FT /evidence="ECO:0007829|PDB:4DVQ" FT HELIX 218..238 FT /evidence="ECO:0007829|PDB:4DVQ" FT HELIX 242..248 FT /evidence="ECO:0007829|PDB:4DVQ" FT HELIX 250..280 FT /evidence="ECO:0007829|PDB:4DVQ" FT HELIX 289..296 FT /evidence="ECO:0007829|PDB:4DVQ" FT HELIX 301..313 FT /evidence="ECO:0007829|PDB:4DVQ" FT HELIX 317..332 FT /evidence="ECO:0007829|PDB:4DVQ" FT HELIX 334..353 FT /evidence="ECO:0007829|PDB:4DVQ" FT HELIX 355..357 FT /evidence="ECO:0007829|PDB:4DVQ" FT HELIX 358..361 FT /evidence="ECO:0007829|PDB:4DVQ" FT HELIX 363..375 FT /evidence="ECO:0007829|PDB:4DVQ" FT STRAND 381..385 FT /evidence="ECO:0007829|PDB:4DVQ" FT STRAND 390..392 FT /evidence="ECO:0007829|PDB:4DVQ" FT STRAND 395..397 FT /evidence="ECO:0007829|PDB:4DVQ" FT STRAND 402..406 FT /evidence="ECO:0007829|PDB:4DVQ" FT HELIX 407..410 FT /evidence="ECO:0007829|PDB:4DVQ" FT TURN 414..416 FT /evidence="ECO:0007829|PDB:4DVQ" FT STRAND 417..419 FT /evidence="ECO:0007829|PDB:4DVQ" FT HELIX 427..430 FT /evidence="ECO:0007829|PDB:4DVQ" FT HELIX 446..448 FT /evidence="ECO:0007829|PDB:4FDH" FT HELIX 453..470 FT /evidence="ECO:0007829|PDB:4DVQ" FT STRAND 471..474 FT /evidence="ECO:0007829|PDB:4DVQ" FT STRAND 483..493 FT /evidence="ECO:0007829|PDB:4DVQ" FT STRAND 497..501 FT /evidence="ECO:0007829|PDB:4DVQ" SQ SEQUENCE 503 AA; 57560 MW; 42BA671704CEE35D CRC64; MALRAKAEVC VAAPWLSLQR ARALGTRAAR APRTVLPFEA MPQHPGNRWL RLLQIWREQG YEHLHLEMHQ TFQELGPIFR YNLGGPRMVC VMLPEDVEKL QQVDSLHPCR MILEPWVAYR QHRGHKCGVF LLNGPEWRFN RLRLNPDVLS PKAVQRFLPM VDAVARDFSQ ALKKKVLQNA RGSLTLDVQP SIFHYTIEAS NLALFGERLG LVGHSPSSAS LNFLHALEVM FKSTVQLMFM PRSLSRWISP KVWKEHFEAW DCIFQYGDNC IQKIYQELAF NRPQHYTGIV AELLLKAELS LEAIKANSME LTAGSVDTTA FPLLMTLFEL ARNPDVQQIL RQESLAAAAS ISEHPQKATT ELPLLRAALK ETLRLYPVGL FLERVVSSDL VLQNYHIPAG TLVQVFLYSL GRNAALFPRP ERYNPQRWLD IRGSGRNFHH VPFGFGMRQC LGRRLAEAEM LLLLHHVLKH FLVETLTQED IKMVYSFILR PGTSPLLTFR AIN //