C11B1_HUMAN
ID C11B1_HUMAN Reviewed; 503 AA.
AC P15538; Q14095; Q4VAQ8; Q4VAQ9; Q9UML2;
DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot.
DT 25-NOV-2008, sequence version 5.
DT 03-AUG-2022, entry version 217.
DE RecName: Full=Cytochrome P450 11B1, mitochondrial;
DE AltName: Full=CYPXIB1;
DE AltName: Full=Cytochrome P-450c11;
DE Short=Cytochrome P450C11;
DE AltName: Full=Steroid 11-beta-hydroxylase, CYP11B1 {ECO:0000303|PubMed:2592361};
DE EC=1.14.15.4 {ECO:0000269|PubMed:18215163};
DE Flags: Precursor;
GN Name=CYP11B1 {ECO:0000303|PubMed:18215163, ECO:0000312|HGNC:HGNC:2591};
GN Synonyms=S11BH;
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], AND VARIANT CYS-494.
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] (ISOFORM 1), PARTIAL PROTEIN SEQUENCE, AND
RP VARIANTS GLN-43 AND VAL-386.
RX PubMed=2401360; DOI=10.1016/0014-5793(90)81190-y;
RA Kawamoto T., Mitsuuchi Y., Toda K., Miyahara K., Yokoyama Y., Nakao K.,
RA Hosoda K., Yamamoto Y., Imura H., Shizuta Y.;
RT "Cloning of cDNA and genomic DNA for human cytochrome P-45011 beta.";
RL FEBS Lett. 269:345-349(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RG NHLBI resequencing and genotyping service (RS&G);
RL Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-132.
RC TISSUE=Peripheral blood;
RX PubMed=7903314; DOI=10.1210/jcem.77.6.7903314;
RA Naiki Y., Kawamoto T., Mitsuuchi Y., Miyahara K., Toda K., Orii T.,
RA Imura H., Shizuta Y.;
RT "A nonsense mutation (TGG [Trp116]-->TAG [Stop]) in CYP11B1 causes steroid
RT 11 beta-hydroxylase deficiency.";
RL J. Clin. Endocrinol. Metab. 77:1677-1682(1993).
RN [8]
RP PRELIMINARY NUCLEOTIDE SEQUENCE [MRNA] OF 216-466, AND VARIANT VAL-386.
RX PubMed=3499608; DOI=10.1073/pnas.84.20.7193;
RA Chua S.C., Szabo P., Vitek A., Grzeschik K.H., John M., White P.C.;
RT "Cloning of cDNA encoding steroid 11 beta-hydroxylase (P450c11).";
RL Proc. Natl. Acad. Sci. U.S.A. 84:7193-7197(1987).
RN [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-30.
RX PubMed=1741400; DOI=10.1073/pnas.89.4.1458;
RA Kawamoto T., Mitsuuchi Y., Toda K., Yokoyama Y., Miyahara K., Miura S.,
RA Ohnishi T., Icikawa Y., Nakao K., Imura H., Ulick S., Shuzuta Y.;
RT "Role of steroid 11 beta-hydroxylase and steroid 18-hydroxylase in the
RT biosynthesis of glucocorticoids and mineralocorticoids in humans.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:1458-1462(1992).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND PATHWAY.
RX PubMed=18215163; DOI=10.1111/j.1742-4658.2008.06253.x;
RA Zoellner A., Kagawa N., Waterman M.R., Nonaka Y., Takio K., Shiro Y.,
RA Hannemann F., Bernhardt R.;
RT "Purification and functional characterization of human 11beta hydroxylase
RT expressed in Escherichia coli.";
RL FEBS J. 275:799-810(2008).
RN [11]
RP VARIANT AH4 HIS-448.
RX PubMed=2022736; DOI=10.1172/jci115182;
RA White P.C., Dupont J., New M.I., Leiberman E., Hochberg Z., Roesler A.;
RT "A mutation in CYP11B1 (Arg-448-->His) associated with steroid 11 beta-
RT hydroxylase deficiency in Jews of Moroccan origin.";
RL J. Clin. Invest. 87:1664-1667(1991).
RN [12]
RP VARIANTS AH4 SER-42; HIS-133 AND MET-319.
RX PubMed=9302260; DOI=10.1093/hmg/6.11.1829;
RA Joehrer K., Geley S., Strasser-Wozak E.M.C., Azziz R., Wollmann H.A.,
RA Schmitt K., Kofler R., White P.C.;
RT "CYP11B1 mutations causing non-classic adrenal hyperplasia due to 11 beta-
RT hydroxylase deficiency.";
RL Hum. Mol. Genet. 6:1829-1834(1997).
RN [13]
RP VARIANT CYS-494.
RX PubMed=10599751; DOI=10.1210/jcem.84.12.6272-6;
RA Loidi L., Quinteiro C., Barros F., Dominguez F., Barreiro J., Pombo M.;
RT "The C494F variant in the CYP11B1 gene is a sequence polymorphism in the
RT Spanish population.";
RL J. Clin. Endocrinol. Metab. 84:4749-4749(1999).
RN [14]
RP VARIANTS TYR-10; GLN-43; THR-348 AND VAL-386.
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 [15]
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 [16]
RP VARIANTS GLN-43; ILE-160 AND VAL-293.
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 [17]
RP VARIANTS AH4 LEU-94; ARG-318 AND HIS-448.
RX PubMed=16046588; DOI=10.1210/jc.2005-0379;
RA Grigorescu Sido A., Weber M.M., Grigorescu Sido P., Clausmeyer S.,
RA Heinrich U., Schulze E.;
RT "21-Hydroxylase and 11beta-hydroxylase mutations in Romanian patients with
RT classic congenital adrenal hyperplasia.";
RL J. Clin. Endocrinol. Metab. 90:5769-5773(2005).
RN [18]
RP VARIANT AH4 VAL-379.
RX PubMed=20331679; DOI=10.1111/j.1399-0004.2010.01403.x;
RA Kharrat M., Trabelsi S., Chaabouni M., Maazoul F., Kraoua L., Ben Jemaa L.,
RA Gandoura N., Barsaoui S., Morel Y., M'rad R., Chaabouni H.;
RT "Only two mutations detected in 15 Tunisian patients with 11beta-
RT hydroxylase deficiency: the p.Q356X and the novel p.G379V.";
RL Clin. Genet. 78:398-401(2010).
RN [19]
RP VARIANTS AH4 SER-42; GLN-43; SER-83; ILE-88; LEU-94; CYS-116; GLY-116;
RP ARG-125; MET-129; HIS-133; SER-135; LEU-139; PRO-158; LEU-159; VAL-161 DEL;
RP ASP-165; ALA-196; 254-LYS--ALA-259 DEL; ASP-267; PRO-299; VAL-306; ARG-314;
RP ARG-318; MET-318; PRO-318; MET-319; VAL-321; VAL-331; SER-341; CYS-366;
RP ASP-368; GLY-371; GLN-374; GLN-384; GLY-384; VAL-386; ALA-401; HIS-427;
RP PHE-438 DEL; GLY-441; ASP-444; CYS-448; HIS-448; GLN-453 AND SER-489, AND
RP CHARACTERIZATION OF VARIANTS AH4 SER-42; GLN-43; SER-83; ILE-88; LEU-94;
RP CYS-116; GLY-116; ARG-125; MET-129; HIS-133; SER-135; LEU-139; PRO-158;
RP LEU-159; ASP-165; ALA-196; 254-LYS--ALA-259 DEL; PRO-299; ARG-314; MET-318;
RP MET-319; VAL-331; CYS-366; ASP-368; GLY-371; GLN-374; GLN-384; ALA-401;
RP PHE-438 DEL; GLY-441; CYS-448; HIS-448 AND GLN-453.
RX PubMed=20089618; DOI=10.1210/jc.2009-0651;
RA Parajes S., Loidi L., Reisch N., Dhir V., Rose I.T., Hampel R.,
RA Quinkler M., Conway G.S., Castro-Feijoo L., Araujo-Vilar D., Pombo M.,
RA Dominguez F., Williams E.L., Cole T.R., Kirk J.M., Kaminsky E., Rumsby G.,
RA Arlt W., Krone N.;
RT "Functional consequences of seven novel mutations in the CYP11B1 gene: four
RT mutations associated with nonclassic and three mutations causing classic
RT 11{beta}-hydroxylase deficiency.";
RL J. Clin. Endocrinol. Metab. 95:779-788(2010).
RN [20]
RP VARIANT AH4 CYS-454.
RX PubMed=20947076; DOI=10.1016/j.fertnstert.2010.09.035;
RA Wu C., Zhou Q., Wan L., Ni L., Zheng C., Qian Y., Jin J.;
RT "Novel homozygous p.R454C mutation in the CYP11B1 gene leads to 11beta-
RT hydroxylase deficiency in a Chinese patient.";
RL Fertil. Steril. 95:1122-1122(2011).
RN [21]
RP VARIANT AH4 ILE-79, AND CHARACTERIZATION OF VARIANT AH4 ILE-79.
RX PubMed=23940125; DOI=10.1210/jc.2013-1306;
RA Reisch N., Hoegler W., Parajes S., Rose I.T., Dhir V., Goetzinger J.,
RA Arlt W., Krone N.;
RT "A diagnosis not to be missed: nonclassic steroid 11beta-hydroxylase
RT deficiency presenting with premature adrenarche and hirsutism.";
RL J. Clin. Endocrinol. Metab. 98:E1620-E1625(2013).
RN [22]
RP VARIANTS AH4 LEU-150 AND LEU-463 INS, AND CHARACTERIZATION OF VARIANTS AH4
RP LEU-150 AND LEU-463 INS.
RX PubMed=24536089; DOI=10.1530/eje-13-0737;
RA Polat S., Kulle A., Karaca Z., Akkurt I., Kurtoglu S., Kelestimur F.,
RA Groetzinger J., Holterhus P.M., Riepe F.G.;
RT "Characterisation of three novel CYP11B1 mutations in classic and non-
RT classic 11beta-hydroxylase deficiency.";
RL Eur. J. Endocrinol. 170:697-706(2014).
RN [23]
RP VARIANTS AH4 TRP-143; PRO-299; VAL-306; LYS-310 AND GLN-332, AND
RP CHARACTERIZATION OF VARIANTS AH4 TRP-143; VAL-306; LYS-310 AND GLN-332.
RX PubMed=24022297; DOI=10.1038/ejhg.2013.197;
RA Menabo S., Polat S., Baldazzi L., Kulle A.E., Holterhus P.M.,
RA Groetzinger J., Fanelli F., Balsamo A., Riepe F.G.;
RT "Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency:
RT functional consequences of four CYP11B1 mutations.";
RL Eur. J. Hum. Genet. 22:610-616(2014).
RN [24]
RP VARIANTS AH4 GLN-141; ARG-318 AND HIS-448.
RX PubMed=24987415; DOI=10.1155/2014/185974;
RA Dumic K., Yuen T., Grubic Z., Kusec V., Barisic I., New M.I.;
RT "Two novel CYP11B1 gene mutations in patients from two Croatian families
RT with 11 beta-hydroxylase deficiency.";
RL Int. J. Endocrinol. 2014:185974-185979(2014).
RN [25]
RP VARIANTS AH4 LEU-42 AND SER-42, AND CHARACTERIZATION OF VARIANTS AH4 LEU-42
RP AND SER-42.
RX PubMed=26053152; DOI=10.1111/cen.12834;
RA Mooij C.F., Parajes S., Rose I.T., Taylor A.E., Bayraktaroglu T.,
RA Wass J.A., Connell J.M., Ray D.W., Arlt W., Krone N.;
RT "Characterization of the molecular genetic pathology in patients with
RT 11beta-hydroxylase deficiency.";
RL Clin. Endocrinol. (Oxf.) 83:629-635(2015).
RN [26]
RP VARIANTS AH4 ARG-318; GLY-332 AND HIS-448, AND CHARACTERIZATION OF VARIANT
RP GLY-332.
RX PubMed=26476331; DOI=10.1016/j.jsbmb.2015.10.011;
RA Nguyen H.H., Eiden-Plach A., Hannemann F., Malunowicz E.M., Hartmann M.F.,
RA Wudy S.A., Bernhardt R.;
RT "Phenotypic, metabolic, and molecular genetic characterization of six
RT patients with congenital adrenal hyperplasia caused by novel mutations in
RT the CYP11B1 gene.";
RL J. Steroid Biochem. Mol. Biol. 155:126-134(2016).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in the biosynthesis
CC of adrenal corticoids (PubMed:18215163). Catalyzes the hydroxylation of
CC carbon hydrogen bond at 11-beta position of 11-deoxycortisol and 11-
CC deoxycorticosterone/21-hydroxyprogesterone yielding cortisol or
CC corticosterone, respectively (PubMed:18215163). Mechanistically, uses
CC molecular oxygen inserting one oxygen atom into a substrate and
CC reducing the second into a water molecule. Two electrons are provided
CC by NADPH via a two-protein mitochondrial transfer system comprising
CC flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and nonheme iron-
CC sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin) (PubMed:18215163).
CC {ECO:0000269|PubMed:18215163}.
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:18215163};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15630;
CC Evidence={ECO:0000305|PubMed:18215163};
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:18215163};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46101;
CC Evidence={ECO:0000305|PubMed:18215163};
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:18215163};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46105;
CC Evidence={ECO:0000305|PubMed:18215163};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P19099};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=338.4 uM for 11-deoxycortisol {ECO:0000269|PubMed:18215163};
CC KM=179.5 uM for 21-hydroxyprogesterone {ECO:0000269|PubMed:18215163};
CC Note=kcat is 1.67 sec(-1) with 11-deoxycortisol as substrate. kcat is
CC 0.85 sec(-1) with 21-hydroxyprogesterone as substrate.
CC {ECO:0000269|PubMed:18215163};
CC -!- PATHWAY: Steroid biosynthesis; glucocorticoid biosynthesis.
CC {ECO:0000269|PubMed:18215163}.
CC -!- PATHWAY: Steroid hormone biosynthesis. {ECO:0000269|PubMed:18215163}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion inner membrane
CC {ECO:0000250|UniProtKB:P14137}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:P14137}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P15538-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P15538-2; Sequence=VSP_043308;
CC -!- DISEASE: Adrenal hyperplasia 4 (AH4) [MIM:202010]: A form of congenital
CC adrenal hyperplasia, a common recessive disease due to defective
CC synthesis of cortisol. Congenital adrenal hyperplasia is characterized
CC by androgen excess leading to ambiguous genitalia in affected females,
CC rapid somatic growth during childhood in both sexes with premature
CC closure of the epiphyses and short adult stature. Four clinical types:
CC 'salt wasting' (SW, the most severe type), 'simple virilizing' (SV,
CC less severely affected patients), with normal aldosterone biosynthesis,
CC 'non-classic form' or late-onset (NC or LOAH) and 'cryptic'
CC (asymptomatic). {ECO:0000269|PubMed:16046588,
CC ECO:0000269|PubMed:20089618, ECO:0000269|PubMed:2022736,
CC ECO:0000269|PubMed:20331679, ECO:0000269|PubMed:20947076,
CC ECO:0000269|PubMed:23940125, ECO:0000269|PubMed:24022297,
CC ECO:0000269|PubMed:24536089, ECO:0000269|PubMed:24987415,
CC ECO:0000269|PubMed:26053152, ECO:0000269|PubMed:26476331,
CC ECO:0000269|PubMed:9302260}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Hyperaldosteronism, familial, 1 (HALD1) [MIM:103900]: A
CC disorder characterized by hypertension, variable hyperaldosteronism,
CC and abnormal adrenal steroid production, including 18-oxocortisol and
CC 18-hydroxycortisol. There is significant phenotypic heterogeneity, and
CC some individuals never develop hypertension. Note=The disease is caused
CC by variants affecting the gene represented in this entry. The molecular
CC defect causing hyperaldosteronism familial 1 is an anti-Lepore-type
CC fusion of the CYP11B1 and CYP11B2 genes. The hybrid gene has the
CC promoting part of CYP11B1, ACTH-sensitive, and the coding part of
CC CYP11B2.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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; M32879; AAA52149.1; -; Genomic_DNA.
DR EMBL; M32863; AAA52149.1; JOINED; Genomic_DNA.
DR EMBL; M32878; AAA52149.1; JOINED; Genomic_DNA.
DR EMBL; X55764; CAA39290.1; -; mRNA.
DR EMBL; D16153; BAB71992.1; -; Genomic_DNA.
DR EMBL; D16155; BAA03717.1; -; Genomic_DNA.
DR EMBL; EU332839; ABY87528.1; -; Genomic_DNA.
DR EMBL; AC083841; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471162; EAW82293.1; -; Genomic_DNA.
DR EMBL; BC096286; AAH96286.1; -; mRNA.
DR EMBL; BC096287; AAH96287.1; -; mRNA.
DR EMBL; M24667; AAA52148.1; ALT_SEQ; mRNA.
DR EMBL; D10169; BAA01039.1; -; Genomic_DNA.
DR CCDS; CCDS34953.1; -. [P15538-2]
DR CCDS; CCDS6392.1; -. [P15538-1]
DR PIR; S11338; S11338.
DR RefSeq; NP_000488.3; NM_000497.3. [P15538-1]
DR RefSeq; NP_001021384.1; NM_001026213.1. [P15538-2]
DR PDB; 6M7X; X-ray; 2.10 A; A/B=31-503.
DR PDB; 7E7F; X-ray; 1.40 A; A=28-503.
DR PDBsum; 6M7X; -.
DR PDBsum; 7E7F; -.
DR AlphaFoldDB; P15538; -.
DR SMR; P15538; -.
DR BioGRID; 107956; 3.
DR IntAct; P15538; 1.
DR STRING; 9606.ENSP00000292427; -.
DR BindingDB; P15538; -.
DR ChEMBL; CHEMBL1908; -.
DR DrugBank; DB04630; Aldosterone.
DR DrugBank; DB00501; Cimetidine.
DR DrugBank; DB01234; Dexamethasone.
DR DrugBank; DB14649; Dexamethasone acetate.
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; DB01026; Ketoconazole.
DR DrugBank; DB05667; Levoketoconazole.
DR DrugBank; DB01011; Metyrapone.
DR DrugBank; DB01388; Mibefradil.
DR DrugBank; DB01110; Miconazole.
DR DrugBank; DB00648; Mitotane.
DR DrugBank; DB11837; Osilodrostat.
DR DrugBank; DB00252; Phenytoin.
DR DrugBank; DB00421; Spironolactone.
DR DrugCentral; P15538; -.
DR GuidetoPHARMACOLOGY; 1359; -.
DR SwissLipids; SLP:000001197; -.
DR iPTMnet; P15538; -.
DR PhosphoSitePlus; P15538; -.
DR BioMuta; CYP11B1; -.
DR DMDM; 215274267; -.
DR MassIVE; P15538; -.
DR PaxDb; P15538; -.
DR PeptideAtlas; P15538; -.
DR PRIDE; P15538; -.
DR ProteomicsDB; 53185; -. [P15538-1]
DR ProteomicsDB; 53186; -. [P15538-2]
DR Antibodypedia; 27799; 236 antibodies from 23 providers.
DR DNASU; 1584; -.
DR Ensembl; ENST00000292427.10; ENSP00000292427.5; ENSG00000160882.13. [P15538-1]
DR Ensembl; ENST00000517471.5; ENSP00000428043.1; ENSG00000160882.13. [P15538-2]
DR GeneID; 1584; -.
DR KEGG; hsa:1584; -.
DR MANE-Select; ENST00000292427.10; ENSP00000292427.5; NM_000497.4; NP_000488.3.
DR UCSC; uc003yxi.4; human. [P15538-1]
DR CTD; 1584; -.
DR DisGeNET; 1584; -.
DR GeneCards; CYP11B1; -.
DR HGNC; HGNC:2591; CYP11B1.
DR HPA; ENSG00000160882; Tissue enriched (adrenal).
DR MalaCards; CYP11B1; -.
DR MIM; 103900; phenotype.
DR MIM; 202010; phenotype.
DR MIM; 610613; gene.
DR neXtProt; NX_P15538; -.
DR OpenTargets; ENSG00000160882; -.
DR Orphanet; 90795; Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency.
DR Orphanet; 403; Familial hyperaldosteronism type I.
DR PharmGKB; PA133; -.
DR VEuPathDB; HostDB:ENSG00000160882; -.
DR eggNOG; KOG0159; Eukaryota.
DR GeneTree; ENSGT00940000163354; -.
DR HOGENOM; CLU_001570_28_4_1; -.
DR InParanoid; P15538; -.
DR OMA; EDIHLEM; -.
DR PhylomeDB; P15538; -.
DR TreeFam; TF105094; -.
DR BioCyc; MetaCyc:HS08547-MON; -.
DR BRENDA; 1.14.15.4; 2681.
DR PathwayCommons; P15538; -.
DR Reactome; R-HSA-194002; Glucocorticoid biosynthesis.
DR Reactome; R-HSA-211976; Endogenous sterols.
DR Reactome; R-HSA-5579017; Defective CYP11B1 causes AH4.
DR SignaLink; P15538; -.
DR SIGNOR; P15538; -.
DR UniPathway; UPA00788; -.
DR BioGRID-ORCS; 1584; 14 hits in 1063 CRISPR screens.
DR ChiTaRS; CYP11B1; human.
DR GeneWiki; Steroid_11-beta-hydroxylase; -.
DR GenomeRNAi; 1584; -.
DR Pharos; P15538; Tclin.
DR PRO; PR:P15538; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P15538; protein.
DR Bgee; ENSG00000160882; Expressed in right adrenal gland cortex and 79 other tissues.
DR ExpressionAtlas; P15538; baseline and differential.
DR Genevisible; P15538; HS.
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; IC:BHF-UCL.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004507; F:steroid 11-beta-monooxygenase activity; IDA:BHF-UCL.
DR GO; GO:0032342; P:aldosterone biosynthetic process; IDA:BHF-UCL.
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; IDA:BHF-UCL.
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:0042593; P:glucose homeostasis; TAS:BHF-UCL.
DR GO; GO:0006955; P:immune response; TAS:BHF-UCL.
DR GO; GO:0008217; P:regulation of blood pressure; IMP:BHF-UCL.
DR GO; GO:0016125; P:sterol metabolic process; TAS:Reactome.
DR Gene3D; 1.10.630.10; -; 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 Pfam; PF00067; p450; 1.
DR PRINTS; PR00408; MITP450.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Congenital adrenal hyperplasia;
KW Direct protein sequencing; Disease variant; Heme; Iron; Lipid biosynthesis;
KW Lipid metabolism; Membrane; Metal-binding; Mitochondrion;
KW Mitochondrion inner membrane; Monooxygenase; Oxidoreductase;
KW Reference proteome; Steroid biosynthesis; Steroidogenesis; Transit peptide.
FT TRANSIT 1..24
FT /note="Mitochondrion"
FT CHAIN 25..503
FT /note="Cytochrome P450 11B1, mitochondrial"
FT /id="PRO_0000003596"
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:0000250|UniProtKB:P19099"
FT VAR_SEQ 401..466
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_043308"
FT VARIANT 10
FT /note="C -> Y (in dbSNP:rs6405)"
FT /evidence="ECO:0000269|PubMed:10391209"
FT /id="VAR_014145"
FT VARIANT 42
FT /note="P -> L (in AH4; classic; highly decreases steroid
FT 11-beta-hydroxylase activity; dbSNP:rs193922538)"
FT /evidence="ECO:0000269|PubMed:26053152"
FT /id="VAR_074493"
FT VARIANT 42
FT /note="P -> S (in AH4; non-classic; highly decreases
FT steroid 11-beta-hydroxylase activity; dbSNP:rs104894069)"
FT /evidence="ECO:0000269|PubMed:20089618,
FT ECO:0000269|PubMed:26053152, ECO:0000269|PubMed:9302260"
FT /id="VAR_001260"
FT VARIANT 43
FT /note="R -> Q (in AH4; decreases steroid 11-beta-
FT hydroxylase activity; dbSNP:rs4534)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:10391210, ECO:0000269|PubMed:20089618,
FT ECO:0000269|PubMed:2401360"
FT /id="VAR_014146"
FT VARIANT 63
FT /note="D -> H (in dbSNP:rs5282)"
FT /id="VAR_014638"
FT VARIANT 79
FT /note="F -> I (in AH4; non-classic; highly decreases
FT steroid 11-beta-hydroxylase activity; dbSNP:rs1489638195)"
FT /evidence="ECO:0000269|PubMed:23940125"
FT /id="VAR_074494"
FT VARIANT 83
FT /note="L -> S (in AH4; highly decreases steroid 11-beta-
FT hydroxylase activity)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074495"
FT VARIANT 88
FT /note="M -> I (in AH4; slightly decreases steroid 11-beta-
FT hydroxylase activity; dbSNP:rs193922539)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074496"
FT VARIANT 94
FT /note="P -> L (in AH4; almost abolishes steroid 11-beta-
FT hydroxylase activity; dbSNP:rs104894070)"
FT /evidence="ECO:0000269|PubMed:16046588,
FT ECO:0000269|PubMed:20089618"
FT /id="VAR_065666"
FT VARIANT 116
FT /note="W -> C (in AH4; almost abolishes steroid 11-beta-
FT hydroxylase activity; dbSNP:rs772003869)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074497"
FT VARIANT 116
FT /note="W -> G (in AH4; abolishes steroid 11-beta-
FT hydroxylase activity; dbSNP:rs772733691)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074498"
FT VARIANT 125
FT /note="H -> R (in AH4; slightly decreases steroid 11-beta-
FT hydroxylase activity; dbSNP:rs757389720)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074499"
FT VARIANT 129
FT /note="V -> M (in AH4; abolishes steroid 11-beta-
FT hydroxylase activity; dbSNP:rs377423817)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074500"
FT VARIANT 133
FT /note="N -> H (in AH4; non-classic; highly decreases
FT steroid 11-beta-hydroxylase activity; dbSNP:rs104894067)"
FT /evidence="ECO:0000269|PubMed:20089618,
FT ECO:0000269|PubMed:9302260"
FT /id="VAR_001261"
FT VARIANT 135
FT /note="P -> S (in AH4; highly decreases steroid 11-beta-
FT hydroxylase activity)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074501"
FT VARIANT 139
FT /note="F -> L (in AH4; decreases steroid 11-beta-
FT hydroxylase activity)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074502"
FT VARIANT 141
FT /note="R -> Q (in AH4; unknown pathological significance;
FT dbSNP:rs267601810)"
FT /evidence="ECO:0000269|PubMed:24987415"
FT /id="VAR_075553"
FT VARIANT 143
FT /note="R -> W (in AH4; non-classic; highly decreases
FT steroid 11-beta-hydroxylase activity; dbSNP:rs140336749)"
FT /evidence="ECO:0000269|PubMed:24022297"
FT /id="VAR_074503"
FT VARIANT 150
FT /note="S -> L (in AH4; non-classic; highly decreases
FT steroid 11-beta-hydroxylase activity; dbSNP:rs142484434)"
FT /evidence="ECO:0000269|PubMed:24536089"
FT /id="VAR_074504"
FT VARIANT 158
FT /note="L -> P (in AH4; highly decreases steroid 11-beta-
FT hydroxylase activity; dbSNP:rs1554653191)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074505"
FT VARIANT 159
FT /note="P -> L (in AH4; decreases steroid 11-beta-
FT hydroxylase activity; dbSNP:rs370266763)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074506"
FT VARIANT 160
FT /note="M -> I (in dbSNP:rs5287)"
FT /evidence="ECO:0000269|PubMed:10391210"
FT /id="VAR_014147"
FT VARIANT 161
FT /note="Missing (in AH4)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074507"
FT VARIANT 165
FT /note="A -> D (in AH4; almost abolishes steroid 11-beta-
FT hydroxylase activity; dbSNP:rs1554653185)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074508"
FT VARIANT 173
FT /note="K -> R (in dbSNP:rs142163070)"
FT /id="VAR_014639"
FT VARIANT 196
FT /note="T -> A (in AH4; decreases steroid 11-beta-
FT hydroxylase activity)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074509"
FT VARIANT 248
FT /note="T -> I (in dbSNP:rs34620645)"
FT /id="VAR_048462"
FT VARIANT 254..259
FT /note="Missing (in AH4; abolishes steroid 11-beta-
FT hydroxylase activity)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074510"
FT VARIANT 257
FT /note="F -> L (in dbSNP:rs5288)"
FT /id="VAR_014640"
FT VARIANT 267
FT /note="G -> D (in AH4)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074511"
FT VARIANT 281
FT /note="S -> N (in dbSNP:rs5291)"
FT /id="VAR_014641"
FT VARIANT 293
FT /note="L -> V (in dbSNP:rs5292)"
FT /evidence="ECO:0000269|PubMed:10391210"
FT /id="VAR_014148"
FT VARIANT 299
FT /note="L -> P (in AH4; non-classic; almost abolishes
FT steroid 11-beta-hydroxylase activity; dbSNP:rs387907573)"
FT /evidence="ECO:0000269|PubMed:20089618,
FT ECO:0000269|PubMed:24022297"
FT /id="VAR_074512"
FT VARIANT 306
FT /note="A -> V (in AH4; non-classic; almost abolishes
FT steroid 11-beta-hydroxylase activity; dbSNP:rs387907572)"
FT /evidence="ECO:0000269|PubMed:20089618,
FT ECO:0000269|PubMed:24022297"
FT /id="VAR_074513"
FT VARIANT 310
FT /note="E -> K (in AH4; abolishes steroid 11-beta-
FT hydroxylase activity; dbSNP:rs387907574)"
FT /evidence="ECO:0000269|PubMed:24022297"
FT /id="VAR_074514"
FT VARIANT 314
FT /note="G -> R (in AH4; abolishes steroid 11-beta-
FT hydroxylase activity; dbSNP:rs1336285846)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074515"
FT VARIANT 318
FT /note="T -> M (in AH4; abolishes steroid 11-beta-
FT hydroxylase activity; dbSNP:rs104894061)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_001262"
FT VARIANT 318
FT /note="T -> P (in AH4; dbSNP:rs1296969984)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074516"
FT VARIANT 318
FT /note="T -> R (in AH4; dbSNP:rs104894061)"
FT /evidence="ECO:0000269|PubMed:16046588,
FT ECO:0000269|PubMed:20089618, ECO:0000269|PubMed:24987415,
FT ECO:0000269|PubMed:26476331"
FT /id="VAR_065667"
FT VARIANT 319
FT /note="T -> M (in AH4; non-classic; decreases steroid 11-
FT beta-hydroxylase activity; dbSNP:rs104894068)"
FT /evidence="ECO:0000269|PubMed:20089618,
FT ECO:0000269|PubMed:9302260"
FT /id="VAR_001263"
FT VARIANT 321
FT /note="F -> V (in AH4; dbSNP:rs1453371113)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074517"
FT VARIANT 331
FT /note="A -> V (in AH4; abolishes steroid 11-beta-
FT hydroxylase activity; dbSNP:rs1326688256)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074518"
FT VARIANT 332
FT /note="R -> G (in AH4; high reduction of steroid 11-beta-
FT monooxygenase activity)"
FT /evidence="ECO:0000269|PubMed:26476331"
FT /id="VAR_075554"
FT VARIANT 332
FT /note="R -> Q (in AH4; non-classic; highly decreases
FT steroid 11-beta-hydroxylase activity; dbSNP:rs149881706)"
FT /evidence="ECO:0000269|PubMed:24022297"
FT /id="VAR_074519"
FT VARIANT 341
FT /note="R -> S (in AH4; dbSNP:rs372115638)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074520"
FT VARIANT 348
FT /note="A -> T (in dbSNP:rs6407)"
FT /evidence="ECO:0000269|PubMed:10391209"
FT /id="VAR_014149"
FT VARIANT 366
FT /note="R -> C (in AH4; decreases steroid 11-beta-
FT hydroxylase activity; dbSNP:rs773245244)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074521"
FT VARIANT 368
FT /note="A -> D (in AH4; abolishes steroid 11-beta-
FT hydroxylase activity; dbSNP:rs104894071)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074522"
FT VARIANT 371
FT /note="E -> G (in AH4; abolishes steroid 11-beta-
FT hydroxylase activity; dbSNP:rs368944209)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074523"
FT VARIANT 374
FT /note="R -> Q (in AH4; abolishes steroid 11-beta-
FT hydroxylase activity; dbSNP:rs104894062)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_001264"
FT VARIANT 379
FT /note="G -> V (in AH4)"
FT /evidence="ECO:0000269|PubMed:20331679"
FT /id="VAR_065196"
FT VARIANT 384
FT /note="R -> G (in AH4)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074524"
FT VARIANT 384
FT /note="R -> Q (in AH4; abolishes steroid 11-beta-
FT hydroxylase activity; dbSNP:rs764598023)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074525"
FT VARIANT 386
FT /note="A -> V (in dbSNP:rs4541)"
FT /evidence="ECO:0000269|PubMed:10391209,
FT ECO:0000269|PubMed:20089618, ECO:0000269|PubMed:2401360,
FT ECO:0000269|PubMed:3499608"
FT /id="VAR_014150"
FT VARIANT 401
FT /note="T -> A (in AH4; decreases steroid 11-beta-
FT hydroxylase activity; dbSNP:rs201300785)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074526"
FT VARIANT 404
FT /note="R -> H (in dbSNP:rs4998896)"
FT /id="VAR_048463"
FT VARIANT 427
FT /note="R -> H (in AH4; dbSNP:rs754432887)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074527"
FT VARIANT 438
FT /note="Missing (in AH4; abolishes steroid 11-beta-
FT hydroxylase activity)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074528"
FT VARIANT 439
FT /note="Y -> H (in dbSNP:rs5294)"
FT /id="VAR_014642"
FT VARIANT 441
FT /note="V -> G (in AH4; abolishes steroid 11-beta-
FT hydroxylase activity; dbSNP:rs772169059)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074529"
FT VARIANT 444
FT /note="G -> D (in AH4; dbSNP:rs779103938)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074530"
FT VARIANT 448
FT /note="R -> C (in AH4; abolishes steroid 11-beta-
FT hydroxylase activity; dbSNP:rs1221010438)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074531"
FT VARIANT 448
FT /note="R -> H (in AH4; abolishes steroid 11-beta-
FT hydroxylase activity; dbSNP:rs28934586)"
FT /evidence="ECO:0000269|PubMed:16046588,
FT ECO:0000269|PubMed:20089618, ECO:0000269|PubMed:2022736,
FT ECO:0000269|PubMed:24987415, ECO:0000269|PubMed:26476331"
FT /id="VAR_001265"
FT VARIANT 453
FT /note="R -> Q (in AH4; abolishes steroid 11-beta-
FT hydroxylase activity; dbSNP:rs1447069098)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074532"
FT VARIANT 454
FT /note="R -> C (in AH4; dbSNP:rs1563867899)"
FT /evidence="ECO:0000269|PubMed:20947076"
FT /id="VAR_065197"
FT VARIANT 463
FT /note="L -> LL (in AH4; classic; abolishes steroid 11-beta-
FT hydroxylase activity)"
FT /evidence="ECO:0000269|PubMed:24536089"
FT /id="VAR_074533"
FT VARIANT 489
FT /note="L -> S (in AH4; dbSNP:rs750428278)"
FT /evidence="ECO:0000269|PubMed:20089618"
FT /id="VAR_074534"
FT VARIANT 494
FT /note="F -> C"
FT /evidence="ECO:0000269|PubMed:10599751,
FT ECO:0000269|PubMed:2592361"
FT /id="VAR_008687"
FT HELIX 38..40
FT /evidence="ECO:0007829|PDB:7E7F"
FT HELIX 52..59
FT /evidence="ECO:0007829|PDB:7E7F"
FT TURN 60..63
FT /evidence="ECO:0007829|PDB:7E7F"
FT HELIX 64..75
FT /evidence="ECO:0007829|PDB:7E7F"
FT STRAND 77..83
FT /evidence="ECO:0007829|PDB:7E7F"
FT STRAND 86..91
FT /evidence="ECO:0007829|PDB:7E7F"
FT HELIX 94..102
FT /evidence="ECO:0007829|PDB:7E7F"
FT HELIX 114..123
FT /evidence="ECO:0007829|PDB:7E7F"
FT TURN 129..131
FT /evidence="ECO:0007829|PDB:7E7F"
FT HELIX 134..148
FT /evidence="ECO:0007829|PDB:7E7F"
FT HELIX 151..178
FT /evidence="ECO:0007829|PDB:7E7F"
FT STRAND 182..186
FT /evidence="ECO:0007829|PDB:7E7F"
FT HELIX 189..205
FT /evidence="ECO:0007829|PDB:7E7F"
FT STRAND 213..215
FT /evidence="ECO:0007829|PDB:7E7F"
FT HELIX 218..238
FT /evidence="ECO:0007829|PDB:7E7F"
FT HELIX 242..244
FT /evidence="ECO:0007829|PDB:7E7F"
FT HELIX 245..280
FT /evidence="ECO:0007829|PDB:7E7F"
FT HELIX 289..296
FT /evidence="ECO:0007829|PDB:7E7F"
FT HELIX 301..313
FT /evidence="ECO:0007829|PDB:7E7F"
FT TURN 314..317
FT /evidence="ECO:0007829|PDB:7E7F"
FT HELIX 320..332
FT /evidence="ECO:0007829|PDB:7E7F"
FT HELIX 334..353
FT /evidence="ECO:0007829|PDB:7E7F"
FT HELIX 355..357
FT /evidence="ECO:0007829|PDB:7E7F"
FT HELIX 358..361
FT /evidence="ECO:0007829|PDB:7E7F"
FT HELIX 363..375
FT /evidence="ECO:0007829|PDB:7E7F"
FT STRAND 378..385
FT /evidence="ECO:0007829|PDB:7E7F"
FT STRAND 390..392
FT /evidence="ECO:0007829|PDB:7E7F"
FT STRAND 395..397
FT /evidence="ECO:0007829|PDB:7E7F"
FT STRAND 402..406
FT /evidence="ECO:0007829|PDB:7E7F"
FT HELIX 407..411
FT /evidence="ECO:0007829|PDB:7E7F"
FT TURN 414..416
FT /evidence="ECO:0007829|PDB:7E7F"
FT STRAND 417..419
FT /evidence="ECO:0007829|PDB:7E7F"
FT HELIX 426..430
FT /evidence="ECO:0007829|PDB:7E7F"
FT HELIX 436..438
FT /evidence="ECO:0007829|PDB:7E7F"
FT HELIX 446..448
FT /evidence="ECO:0007829|PDB:7E7F"
FT HELIX 453..470
FT /evidence="ECO:0007829|PDB:7E7F"
FT STRAND 471..474
FT /evidence="ECO:0007829|PDB:7E7F"
FT STRAND 483..493
FT /evidence="ECO:0007829|PDB:7E7F"
FT STRAND 497..501
FT /evidence="ECO:0007829|PDB:7E7F"
SQ SEQUENCE 503 AA; 57573 MW; 0B36D82513960EE9 CRC64;
MALRAKAEVC MAVPWLSLQR AQALGTRAAR VPRTVLPFEA MPRRPGNRWL RLLQIWREQG
YEDLHLEVHQ TFQELGPIFR YDLGGAGMVC VMLPEDVEKL QQVDSLHPHR MSLEPWVAYR
QHRGHKCGVF LLNGPEWRFN RLRLNPEVLS PNAVQRFLPM VDAVARDFSQ ALKKKVLQNA
RGSLTLDVQP SIFHYTIEAS NLALFGERLG LVGHSPSSAS LNFLHALEVM FKSTVQLMFM
PRSLSRWTSP KVWKEHFEAW DCIFQYGDNC IQKIYQELAF SRPQQYTSIV AELLLNAELS
PDAIKANSME LTAGSVDTTV FPLLMTLFEL ARNPNVQQAL RQESLAAAAS ISEHPQKATT
ELPLLRAALK ETLRLYPVGL FLERVASSDL VLQNYHIPAG TLVRVFLYSL GRNPALFPRP
ERYNPQRWLD IRGSGRNFYH VPFGFGMRQC LGRRLAEAEM LLLLHHVLKH LQVETLTQED
IKMVYSFILR PSMFPLLTFR AIN
