P15538 (C11B1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cytochrome P450 11B1, mitochondrial

Alternative name(s):
CYPXIB1
Cytochrome P-450c11
Short name=Cytochrome P450C11
Steroid 11-beta-hydroxylase
EC=1.14.15.4

Gene names

Name:	CYP11B1
Synonyms:	S11BH

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	Has steroid 11-beta-hydroxylase activity. In addition to this activity, the 18 or 19-hydroxylation of steroids and the aromatization of androstendione to estrone have also been ascribed to cytochrome P450 XIB.
Catalytic activity	A steroid + reduced adrenal ferredoxin + O2 = an 11-beta-hydroxysteroid + oxidized adrenal ferredoxin + H2O.
Cofactor	Heme group By similarity.
Subcellular location	Mitochondrion membrane.
Involvement in disease	Defects in CYP11B1 are the cause of adrenal hyperplasia type 4 (AH4) [MIM:202010]. AH4 is a form of congenital adrenal hyperplasia, a common recessive disease due to defective synthesis of cortisol. Congenital adrenal hyperplasia is characterized by androgen excess leading to ambiguous genitalia in affected females, rapid somatic growth during childhood in both sexes with premature closure of the epiphyses and short adult stature. Four clinical types: "salt wasting" (SW, the most severe type), "simple virilizing" (SV, less severely affected patients), with normal aldosterone biosynthesis, "non-classic form" or late onset (NC or LOAH), and "cryptic" (asymptomatic). AH4 patients usually have hypertension. Ref.10 Ref.11 Ref.16 Ref.17 Ref.18 Defects in CYP11B1 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.
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	Congenital adrenal hyperplasia Disease mutation
Domain	Transit peptide
Ligand	Heme Iron Metal-binding
Molecular function	Monooxygenase Oxidoreductase
Technical term	Complete proteome Direct protein sequencing 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 glucose homeostasis Traceable author statement. Source: BHF-UCL immune response Traceable author statement. Source: BHF-UCL regulation of blood pressure Inferred from mutant phenotype Ref.10. Source: BHF-UCL response to stress Traceable author statement. Source: BHF-UCL xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular component	mitochondrial inner membrane Traceable author statement. Source: BHF-UCL
Molecular function	electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred by curator. Source: BHF-UCL steroid 11-beta-monooxygenase activity Inferred from direct assay. 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 11B1, mitochondrial		PRO_0000003596
Sites
	Metal binding	450	1	Iron (heme axial ligand) By similarity
Natural variations
	Natural variant	10	1	C → Y. Ref.13 Corresponds to variant rs6405 [ dbSNP | Ensembl ].		VAR_014145
	Natural variant	42	1	P → S in AH4; non-classic. Ref.11		VAR_001260
	Natural variant	43	1	R → Q. Ref.2 Ref.13 Ref.15 Corresponds to variant rs4534 [ dbSNP | Ensembl ].		VAR_014146
	Natural variant	63	1	D → H. Corresponds to variant rs5282 [ dbSNP | Ensembl ].		VAR_014638
	Natural variant	94	1	P → L in AH4. Ref.16		VAR_065666
	Natural variant	133	1	N → H in AH4; non-classic. Ref.11		VAR_001261
	Natural variant	160	1	M → I. Ref.15 Corresponds to variant rs5287 [ dbSNP | Ensembl ].		VAR_014147
	Natural variant	173	1	K → R. Corresponds to variant rs4539 [ dbSNP | Ensembl ].		VAR_014639
	Natural variant	248	1	T → I. Corresponds to variant rs34620645 [ dbSNP | Ensembl ].		VAR_048462
	Natural variant	257	1	F → L. Corresponds to variant rs5288 [ dbSNP | Ensembl ].		VAR_014640
	Natural variant	281	1	S → N. Corresponds to variant rs5291 [ dbSNP | Ensembl ].		VAR_014641
	Natural variant	293	1	L → V. Ref.15 Corresponds to variant rs5292 [ dbSNP | Ensembl ].		VAR_014148
	Natural variant	318	1	T → M in AH4.		VAR_001262
	Natural variant	318	1	T → R in AH4. Ref.16		VAR_065667
	Natural variant	319	1	T → M in AH4; non-classic. Ref.11		VAR_001263
	Natural variant	348	1	A → T. Ref.13 Corresponds to variant rs6407 [ dbSNP | Ensembl ].		VAR_014149
	Natural variant	374	1	R → Q in AH4.		VAR_001264
	Natural variant	379	1	G → V in AH4. Ref.17		VAR_065196
	Natural variant	386	1	A → V. Ref.2 Ref.8 Ref.13 Corresponds to variant rs4541 [ dbSNP | Ensembl ].		VAR_014150
	Natural variant	404	1	R → H. Corresponds to variant rs4998896 [ dbSNP | Ensembl ].		VAR_048463
	Natural variant	439	1	Y → H. Corresponds to variant rs5294 [ dbSNP | Ensembl ].		VAR_014642
	Natural variant	448	1	R → H in AH4. Ref.10 Ref.16 Corresponds to variant rs28934586 [ dbSNP | Ensembl ].		VAR_001265
	Natural variant	454	1	R → C in AH4. Ref.18		VAR_065197
	Natural variant	494	1	F → C. Ref.1 Ref.12		VAR_008687

Sequences

	Sequence		Length	Mass (Da)
	P15538 [UniParc]. Last modified November 25, 2008. Version 5. Checksum: 0B36D82513960EE9	FASTA	503	57,573
	10 20 30 40 50 60 MALRAKAEVC MAVPWLSLQR AQALGTRAAR VPRTVLPFEA MPRRPGNRWL RLLQIWREQG 70 80 90 100 110 120 YEDLHLEVHQ TFQELGPIFR YDLGGAGMVC VMLPEDVEKL QQVDSLHPHR MSLEPWVAYR 130 140 150 160 170 180 QHRGHKCGVF LLNGPEWRFN RLRLNPEVLS PNAVQRFLPM VDAVARDFSQ ALKKKVLQNA 190 200 210 220 230 240 RGSLTLDVQP SIFHYTIEAS NLALFGERLG LVGHSPSSAS LNFLHALEVM FKSTVQLMFM 250 260 270 280 290 300 PRSLSRWTSP KVWKEHFEAW DCIFQYGDNC IQKIYQELAF SRPQQYTSIV AELLLNAELS 310 320 330 340 350 360 PDAIKANSME LTAGSVDTTV FPLLMTLFEL ARNPNVQQAL RQESLAAAAS ISEHPQKATT 370 380 390 400 410 420 ELPLLRAALK ETLRLYPVGL FLERVASSDL VLQNYHIPAG TLVRVFLYSL GRNPALFPRP 430 440 450 460 470 480 ERYNPQRWLD IRGSGRNFYH VPFGFGMRQC LGRRLAEAEM LLLLHHVLKH LQVETLTQED 490 500 IKMVYSFILR PSMFPLLTFR 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], VARIANT CYS-494.
[2]	"Cloning of cDNA and genomic DNA for human cytochrome P-45011 beta." Kawamoto T., Mitsuuchi Y., Toda K., Miyahara K., Yokoyama Y., Nakao K., Hosoda K., Yamamoto Y., Imura H., Shizuta Y. FEBS Lett. 269:345-349(1990) [PubMed: 2401360] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, VARIANTS GLN-43 AND VAL-386.
[3]	NHLBI resequencing and genotyping service (RS&G) Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	"DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S. Nature 439:331-335(2006) [PubMed: 16421571] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE 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]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[7]	"A nonsense mutation (TGG [Trp116]-->TAG [Stop]) in CYP11B1 causes steroid 11 beta-hydroxylase deficiency." Naiki Y., Kawamoto T., Mitsuuchi Y., Miyahara K., Toda K., Orii T., Imura H., Shizuta Y. J. Clin. Endocrinol. Metab. 77:1677-1682(1993) [PubMed: 7903314] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-132. Tissue: Peripheral blood.
[8]	"Cloning of cDNA encoding steroid 11 beta-hydroxylase (P450c11)." Chua S.C., Szabo P., Vitek A., Grzeschik K.H., John M., White P.C. Proc. Natl. Acad. Sci. U.S.A. 84:7193-7197(1987) [PubMed: 3499608] [Abstract] Cited for: PRELIMINARY NUCLEOTIDE SEQUENCE [MRNA] OF 216-466, VARIANT VAL-386.
[9]	"Role of steroid 11 beta-hydroxylase and steroid 18-hydroxylase in the biosynthesis of glucocorticoids and mineralocorticoids in humans." Kawamoto T., Mitsuuchi Y., Toda K., Yokoyama Y., Miyahara K., Miura S., Ohnishi T., Icikawa Y., Nakao K., Imura H., Ulick S., Shuzuta Y. Proc. Natl. Acad. Sci. U.S.A. 89:1458-1462(1992) [PubMed: 1741400] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-30.
[10]	"A mutation in CYP11B1 (Arg-448-->His) associated with steroid 11 beta-hydroxylase deficiency in Jews of Moroccan origin." White P.C., Dupont J., New M.I., Leiberman E., Hochberg Z., Roesler A. J. Clin. Invest. 87:1664-1667(1991) [PubMed: 2022736] [Abstract] Cited for: VARIANT AH4 HIS-448.
[11]	"CYP11B1 mutations causing non-classic adrenal hyperplasia due to 11 beta-hydroxylase deficiency." Joehrer K., Geley S., Strasser-Wozak E.M.C., Azziz R., Wollmann H.A., Schmitt K., Kofler R., White P.C. Hum. Mol. Genet. 6:1829-1834(1997) [PubMed: 9302260] [Abstract] Cited for: VARIANTS AH4 SER-42; HIS-133 AND MET-319.
[12]	"The C494F variant in the CYP11B1 gene is a sequence polymorphism in the Spanish population." Loidi L., Quinteiro C., Barros F., Dominguez F., Barreiro J., Pombo M. J. Clin. Endocrinol. Metab. 84:4749-4749(1999) [PubMed: 10599751] [Abstract] Cited for: VARIANT CYS-494.
[13]	"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 TYR-10; GLN-43; THR-348 AND VAL-386.
[14]	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)
[15]	"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 GLN-43; ILE-160 AND VAL-293.
[16]	"21-Hydroxylase and 11beta-hydroxylase mutations in Romanian patients with classic congenital adrenal hyperplasia." Grigorescu Sido A., Weber M.M., Grigorescu Sido P., Clausmeyer S., Heinrich U., Schulze E. J. Clin. Endocrinol. Metab. 90:5769-5773(2005) [PubMed: 16046588] [Abstract] Cited for: VARIANTS AH4 LEU-94; ARG-318 AND HIS-448.
[17]	"Only two mutations detected in 15 Tunisian patients with 11beta-hydroxylase deficiency: the p.Q356X and the novel p.G379V." Kharrat M., Trabelsi S., Chaabouni M., Maazoul F., Kraoua L., Ben Jemaa L., Gandoura N., Barsaoui S., Morel Y., M'rad R., Chaabouni H. Clin. Genet. 78:398-401(2010) [PubMed: 20331679] [Abstract] Cited for: VARIANT AH4 VAL-379.
[18]	"Novel homozygous p.R454C mutation in the CYP11B1 gene leads to 11beta-hydroxylase deficiency in a Chinese patient." Wu C., Zhou Q., Wan L., Ni L., Zheng C., Qian Y., Jin J. Fertil. Steril. 95:1122-1122(2011) [PubMed: 20947076] [Abstract] Cited for: VARIANT AH4 CYS-454.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases
EMBL GenBank DDBJ	M32879, M32863, M32878 Genomic DNA. Translation: AAA52149.1. X55764 mRNA. Translation: CAA39290.1. D16153 Genomic DNA. Translation: BAB71992.1. D16155 Genomic DNA. Translation: BAA03717.1. EU332839 Genomic DNA. Translation: ABY87528.1. AC083841 Genomic DNA. No translation available. CH471162 Genomic DNA. Translation: EAW82293.1. BC096287 mRNA. Translation: AAH96287.1. M24667 mRNA. Translation: AAA52148.1. Sequence problems. D10169 Genomic DNA. Translation: BAA01039.1.
IPI	IPI00291348.
PIR	S11338.
RefSeq	NP_000488.3. NM_000497.3. NP_001021384.1. NM_001026213.1.
UniGene	Hs.184927.
3D structure databases
ProteinModelPortal	P15538.
SMR	P15538. Positions 35-503.
ModBase	Search...
Protein-protein interaction databases
STRING	P15538.
Polymorphism databases
DMDM	215274267.
Proteomic databases
PRIDE	P15538.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000292427; ENSP00000292427; ENSG00000160882.
GeneID	1584.
KEGG	hsa:1584.
Organism-specific databases
CTD	1584.
GeneCards	GC08M143950.
H-InvDB	HIX0007833.
HGNC	HGNC:2591. CYP11B1.
MIM	103900. phenotype. 202010. phenotype. 610613. gene.
neXtProt	NX_P15538.
Orphanet	90795. Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency. 403. Familial hyperaldosteronism type 1.
PharmGKB	PA133.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG18338.
HOVERGEN	HBG051098.
PhylomeDB	P15538.
Enzyme and pathway databases
BRENDA	1.14.15.4. 2681.
Reactome	REACT_111217. Metabolism. REACT_15493. Steroid hormones. REACT_22258. Metabolism of lipids and lipoproteins.
Gene expression databases
ArrayExpress	P15538.
Bgee	P15538.
CleanEx	HS_CYP11B1.
Genevestigator	P15538.
GermOnline	ENSG00000160882. 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	K00497.
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	DB00648. Mitotane.
SOURCE	Search...

Entry information

Entry name

C11B1_HUMAN

Accession

Primary (citable) accession number: P15538
Secondary accession number(s): Q14095, Q4VAQ8, Q9UML2

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	November 25, 2008
Last modified:	January 25, 2012
This is version 135 of the entry and version 5 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.