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P15538 (C11B1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 157. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length503 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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 adrenodoxin + O2 = an 11-beta-hydroxysteroid + oxidized adrenodoxin + H2O.

Cofactor

Heme group By similarity.

Subcellular location

Mitochondrion membrane.

Involvement in disease

Adrenal hyperplasia 4 (AH4) [MIM:202010]: 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).
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10 Ref.11 Ref.16 Ref.17 Ref.18

Familial hyperaldosteronism 1 (FH1) [MIM:103900]: 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 disease is caused by mutations affecting the gene represented in this entry. The molecular defect causing hyperaldosteronism familial 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 processLipid metabolism
Steroid metabolism
Steroidogenesis
   Cellular componentMembrane
Mitochondrion
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseCongenital adrenal hyperplasia
Disease mutation
   DomainTransit peptide
   LigandHeme
Iron
Metal-binding
   Molecular functionMonooxygenase
Oxidoreductase
   Technical termComplete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processaldosterone biosynthetic process

Inferred from mutant phenotype PubMed 19342457. Source: UniProtKB

cellular response to hormone stimulus

Inferred from expression pattern PubMed 19342457. Source: UniProtKB

cellular response to potassium ion

Inferred from expression pattern PubMed 19342457. Source: UniProtKB

cortisol biosynthetic process

Inferred from mutant phenotype PubMed 19342457. Source: UniProtKB

glucose homeostasis

Traceable author statement PubMed 16114325. Source: BHF-UCL

immune response

Traceable author statement PubMed 12452430. Source: BHF-UCL

regulation of blood pressure

Inferred from mutant phenotype Ref.10. Source: BHF-UCL

sterol metabolic process

Traceable author statement. Source: Reactome

xenobiotic metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentmitochondrial inner membrane

Traceable author statement PubMed 15026188. Source: BHF-UCL

   Molecular_functionheme binding

Inferred by curator PubMed 2256920. Source: BHF-UCL

iron ion binding

Inferred from electronic annotation. Source: InterPro

steroid 11-beta-monooxygenase activity

Inferred from direct assay PubMed 2256920PubMed 8506298. Source: BHF-UCL

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P15538-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P15538-2)

The sequence of this isoform differs from the canonical sequence as follows:
     401-466: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 2424Mitochondrion
Chain25 – 503479Cytochrome P450 11B1, mitochondrial
PRO_0000003596

Sites

Metal binding4501Iron (heme axial ligand) By similarity

Natural variations

Alternative sequence401 – 46666Missing in isoform 2.
VSP_043308
Natural variant101C → Y. Ref.13
Corresponds to variant rs6405 [ dbSNP | Ensembl ].
VAR_014145
Natural variant421P → S in AH4; non-classic. Ref.11
VAR_001260
Natural variant431R → Q. Ref.2 Ref.13 Ref.15
Corresponds to variant rs4534 [ dbSNP | Ensembl ].
VAR_014146
Natural variant631D → H.
Corresponds to variant rs5282 [ dbSNP | Ensembl ].
VAR_014638
Natural variant941P → L in AH4. Ref.16
VAR_065666
Natural variant1331N → H in AH4; non-classic. Ref.11
VAR_001261
Natural variant1601M → I. Ref.15
Corresponds to variant rs5287 [ dbSNP | Ensembl ].
VAR_014147
Natural variant1731K → R.
Corresponds to variant rs4539 [ dbSNP | Ensembl ].
VAR_014639
Natural variant2481T → I.
Corresponds to variant rs34620645 [ dbSNP | Ensembl ].
VAR_048462
Natural variant2571F → L.
Corresponds to variant rs5288 [ dbSNP | Ensembl ].
VAR_014640
Natural variant2811S → N.
Corresponds to variant rs5291 [ dbSNP | Ensembl ].
VAR_014641
Natural variant2931L → V. Ref.15
Corresponds to variant rs5292 [ dbSNP | Ensembl ].
VAR_014148
Natural variant3181T → M in AH4.
VAR_001262
Natural variant3181T → R in AH4. Ref.16
VAR_065667
Natural variant3191T → M in AH4; non-classic. Ref.11
VAR_001263
Natural variant3481A → T. Ref.13
Corresponds to variant rs6407 [ dbSNP | Ensembl ].
VAR_014149
Natural variant3741R → Q in AH4.
VAR_001264
Natural variant3791G → V in AH4. Ref.17
VAR_065196
Natural variant3861A → V. Ref.2 Ref.8 Ref.13
Corresponds to variant rs4541 [ dbSNP | Ensembl ].
VAR_014150
Natural variant4041R → H.
Corresponds to variant rs4998896 [ dbSNP | Ensembl ].
VAR_048463
Natural variant4391Y → H.
Corresponds to variant rs5294 [ dbSNP | Ensembl ].
VAR_014642
Natural variant4481R → H in AH4. Ref.10 Ref.16
Corresponds to variant rs28934586 [ dbSNP | Ensembl ].
VAR_001265
Natural variant4541R → C in AH4. Ref.18
VAR_065197
Natural variant4941F → C. Ref.1 Ref.12
VAR_008687

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified November 25, 2008. Version 5.
Checksum: 0B36D82513960EE9

FASTA50357,573
        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 

« Hide

Isoform 2 [UniParc].

Checksum: F85180BFB83C9B5A
Show »

FASTA43749,750

References

« Hide '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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), 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. expand/collapse author list , 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] [Europe PMC] [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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
[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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: VARIANT AH4 CYS-454.
+Additional computationally mapped references.

Web resources

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.
BC096286 mRNA. Translation: AAH96286.1.
BC096287 mRNA. Translation: AAH96287.1.
M24667 mRNA. Translation: AAA52148.1. Sequence problems.
D10169 Genomic DNA. Translation: BAA01039.1.
PIRS11338.
RefSeqNP_000488.3. NM_000497.3.
NP_001021384.1. NM_001026213.1.
UniGeneHs.184927.

3D structure databases

ProteinModelPortalP15538.
SMRP15538. Positions 34-502.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000292427.

Chemistry

BindingDBP15538.
ChEMBLCHEMBL1908.
DrugBankDB00648. Mitotane.

PTM databases

PhosphoSiteP15538.

Polymorphism databases

DMDM215274267.

Proteomic databases

PaxDbP15538.
PRIDEP15538.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000292427; ENSP00000292427; ENSG00000160882. [P15538-1]
ENST00000517471; ENSP00000428043; ENSG00000160882. [P15538-2]
GeneID1584.
KEGGhsa:1584.
UCSCuc003yxi.3. human. [P15538-1]
uc003yxj.3. human. [P15538-2]

Organism-specific databases

CTD1584.
GeneCardsGC08M143950.
HGNCHGNC:2591. CYP11B1.
HPAHPA049171.
MIM103900. phenotype.
202010. phenotype.
610613. gene.
neXtProtNX_P15538.
Orphanet90795. Congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency.
403. Familial hyperaldosteronism type 1.
PharmGKBPA133.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2124.
HOGENOMHOG000013161.
HOVERGENHBG051098.
KOK00497.
PhylomeDBP15538.
TreeFamTF105094.

Enzyme and pathway databases

BioCycMetaCyc:HS08547-MONOMER.
BRENDA1.14.15.4. 2681.
ReactomeREACT_111217. Metabolism.
REACT_15493. Steroid hormones.

Gene expression databases

ArrayExpressP15538.
BgeeP15538.
CleanExHS_CYP11B1.
GenevestigatorP15538.

Family and domain databases

Gene3D1.10.630.10. 1 hit.
InterProIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002399. Cyt_P450_mitochondrial.
[Graphical view]
PfamPF00067. p450. 1 hit.
[Graphical view]
PRINTSPR00408. MITP450.
PR00385. P450.
SUPFAMSSF48264. SSF48264. 1 hit.
PROSITEPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSteroid_11-beta-hydroxylase.
GenomeRNAi1584.
NextBio6509.
PROP15538.
SOURCESearch...

Entry information

Entry nameC11B1_HUMAN
AccessionPrimary (citable) accession number: P15538
Secondary accession number(s): Q14095 expand/collapse secondary AC list , Q4VAQ8, Q4VAQ9, Q9UML2
Entry history
Integrated into UniProtKB/Swiss-Prot: April 1, 1990
Last sequence update: November 25, 2008
Last modified: March 19, 2014
This is version 157 of the entry and version 5 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM