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Q16678 (CP1B1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 165. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cytochrome P450 1B1

EC=1.14.14.1
Alternative name(s):
CYPIB1
Gene names
Name:CYP1B1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length543 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, retinoid and xenobiotics. Preferentially oxidizes 17beta-estradiol to the carcinogenic 4-hydroxy derivative, and a variety of procarcinogenic compounds to their activated forms, including polycyclic aromatic hydrocarbons. Promotes angiogenesis by removing cellular oxygenation products, thereby decreasing oxidative stress, release of antiangiogenic factor THBS2, then allowing endothelial cells migration, cell adhesion and capillary morphogenesis. These changes are concommitant with the endothelial nitric oxide synthase activity and nitric oxide synthesis. Plays an important role in the regulation of perivascular cell proliferation, migration, and survival through modulation of the intracellular oxidative state and NF-kappa-B expression and/or activity, during angiogenesis. Contributes to oxidative homeostasis and ultrastructural organization and function of trabecular meshwork tissue through modulation of POSTN expression. Ref.8 Ref.10 Ref.11 Ref.12

Catalytic activity

RH + reduced flavoprotein + O2 = ROH + oxidized flavoprotein + H2O. Ref.8 Ref.11

Cofactor

Heme group. Ref.14

Enzyme regulation

Enzyme activity is increased by liposomes containing anionic phospholipids, phosphatidic acid and cardiolipin. Inhibited by naringenin with an IC50 of 5 µM. Ref.11 Ref.13

Subcellular location

Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein. Mitochondrion By similarity.

Tissue specificity

Expressed in many tissues. Ref.1

Induction

By polycyclic aromatic hydrocarbons (PAH) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Ref.1 Ref.11 Ref.13

Polymorphism

Various CYP1B1 alleles are known. The sequence shown is that of allele CYP1B1*1.

Involvement in disease

Peters anomaly (PETAN) [MIM:604229]: Consists of a central corneal leukoma, absence of the posterior corneal stroma and Descemet membrane, and a variable degree of iris and lenticular attachments to the central aspect of the posterior cornea.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.9

Glaucoma 3, primary congenital, A (GLC3A) [MIM:231300]: An autosomal recessive form of primary congenital glaucoma (PCG). PCG is characterized by marked increase of intraocular pressure at birth or early childhood, large ocular globes (buphthalmos) and corneal edema. It results from developmental defects of the trabecular meshwork and anterior chamber angle of the eye that prevent adequate drainage of aqueous humor.
Note: The disease is caused by mutations affecting distinct genetic loci, including the gene represented in this entry. Ref.15 Ref.16 Ref.19 Ref.20 Ref.22 Ref.24 Ref.27 Ref.28 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35 Ref.36 Ref.38 Ref.40

Glaucoma, primary open angle (POAG) [MIM:137760]: A complex and genetically heterogeneous ocular disorder characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. However, glaucoma can occur at any intraocular pressure. The disease is generally asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place. In some cases, POAG shows digenic inheritance involving mutations in CYP1B1 and MYOC genes.
Note: Disease susceptibility is associated with variations affecting the gene represented in this entry. CYP1B1 mutations have been reported to pose a significant risk for early-onset POAG and also modify glaucoma phenotype in patients who do not carry a MYOC mutation (Ref.33). Ref.26 Ref.33 Ref.37 Ref.39 Ref.40

Glaucoma 1, open angle, A (GLC1A) [MIM:137750]: A form of primary open angle glaucoma (POAG). POAG is characterized by a specific pattern of optic nerve and visual field defects. The angle of the anterior chamber of the eye is open, and usually the intraocular pressure is increased. However, glaucoma can occur at any intraocular pressure. The disease is generally asymptomatic until the late stages, by which time significant and irreversible optic nerve damage has already taken place.
Note: The gene represented in this entry acts as a disease modifier. Digenic mutations in CYP1B1 and MYOC have been found in a family segregating both primary adult-onset and juvenile forms of open angle glaucoma (Ref.26). All affected family members with mutations in both MYOC and CYP1B1 had juvenile glaucoma, whereas those with only the MYOC mutation had the adult-onset form (Ref.26). Ref.26

Sequence similarities

Belongs to the cytochrome P450 family.

Biophysicochemical properties

Kinetic parameters:

kcat is 0.15 min(-1) for retinol, 0.77 min(-1) for retinal, 2.86 min(-1) for 7,12-dimethyltetraphene, 0.48 min(-1) for arachidonic acid.

KM=6.0 µM for 17-beta-estradiol Ref.8 Ref.10

KM=17.0 µM for testosterone

KM=24.0 µM for progesterone

KM=18.5 µM for retinol

KM=8.5 µM for retinal

KM=29.8 µM for arachidonic acid

KM=212.8 µM for 7,12-dimethyltetraphene

Vmax=14.95 nmol/min/mg enzyme for 17-beta-estradiol 4-hydroxylation

Vmax=6.9 nmol/min/mg enzyme for 17-beta-estradiol 2-hydroxylation

Vmax=36.16 nmol/min/mg enzyme for testosterone 6-beta-hydroxylation

Vmax=9.86 nmol/min/mg enzyme for progesterone 6-beta-hydroxylation

Vmax=37.80 nmol/min/mg enzyme for progesterone 16-alpha-hydroxylation

Ontologies

Keywords
   Cellular componentEndoplasmic reticulum
Membrane
Microsome
Mitochondrion
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
Glaucoma
Peters anomaly
   LigandHeme
Iron
Metal-binding
   Molecular functionMonooxygenase
Oxidoreductase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processangiogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

arachidonic acid metabolic process

Traceable author statement. Source: Reactome

blood vessel morphogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

cellular aromatic compound metabolic process

Inferred from electronic annotation. Source: Ensembl

cellular response to organic cyclic compound

Inferred from direct assay PubMed 23275542. Source: MGI

endothelial cell migration

Inferred from electronic annotation. Source: Ensembl

endothelial cell-cell adhesion

Inferred from electronic annotation. Source: Ensembl

epoxygenase P450 pathway

Traceable author statement. Source: Reactome

intrinsic apoptotic signaling pathway in response to oxidative stress

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of NF-kappaB transcription factor activity

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell adhesion mediated by integrin

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell migration

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of cell proliferation

Inferred from sequence or structural similarity. Source: UniProtKB

omega-hydroxylase P450 pathway

Traceable author statement. Source: Reactome

oxidation-reduction process

Traceable author statement PubMed 9097971. Source: UniProtKB

positive regulation of JAK-STAT cascade

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of gene expression involved in extracellular matrix organization

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation vascular endothelial growth factor production

Inferred from sequence or structural similarity. Source: UniProtKB

response to toxic substance

Inferred from electronic annotation. Source: Ensembl

retina vasculature development in camera-type eye

Inferred from electronic annotation. Source: Ensembl

small molecule metabolic process

Traceable author statement. Source: Reactome

steroid metabolic process

Inferred from direct assay Ref.11. Source: UniProtKB

sterol metabolic process

Traceable author statement. Source: Reactome

toxin metabolic process

Inferred from electronic annotation. Source: Ensembl

visual perception

Traceable author statement PubMed 9097971. Source: UniProtKB

xenobiotic metabolic process

Inferred from direct assay Ref.11. Source: UniProtKB

   Cellular_componentendoplasmic reticulum membrane

Traceable author statement. Source: Reactome

   Molecular_functionaromatase activity

Inferred from electronic annotation. Source: UniProtKB-EC

heme binding

Inferred from direct assay Ref.14. Source: UniProtKB

iron ion binding

Inferred from electronic annotation. Source: InterPro

monooxygenase activity

Traceable author statement. Source: UniProtKB

oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen

Inferred from direct assay PubMed 10871058. Source: MGI

oxygen binding

Traceable author statement PubMed 9097971. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 543543Cytochrome P450 1B1
PRO_0000051660

Sites

Metal binding4701Iron (heme axial ligand)
Site3951Major determinant of CYP1B1 17beta-estradiol hydroxylation regiospecificity

Natural variations

Natural variant281S → W in POAG. Ref.39
VAR_054227
Natural variant481R → G in allele CYP1B1*2, allele CYP1B1*5, allele CYP1B1*6 and allele CYP1B1*7. Ref.5 Ref.7 Ref.20 Ref.24 Ref.27 Ref.28 Ref.29 Ref.31 Ref.32 Ref.33 Ref.34 Ref.37
Corresponds to variant rs10012 [ dbSNP | Ensembl ].
VAR_011752
Natural variant521P → L. Ref.39
VAR_054228
Natural variant571W → C in POAG; juvenile onset; allele CYP1B1*11. Ref.16 Ref.37
VAR_008350
Natural variant611G → E in GLC3A and POAG; allele CYP1B1*12; reduces enzymatic activity. Ref.15 Ref.16 Ref.20 Ref.27 Ref.36 Ref.38 Ref.39 Ref.40
Corresponds to variant rs28936700 [ dbSNP | Ensembl ].
VAR_001244
Natural variant681Q → R.
Corresponds to variant rs9282670 [ dbSNP | Ensembl ].
VAR_028735
Natural variant771L → P in GLC3A. Ref.20 Ref.34
VAR_054229
Natural variant811Y → N in POAG; adult-onset; hypomorphic allele; reduces the abundance of the enzyme. Ref.33 Ref.38 Ref.39 Ref.40
Corresponds to variant rs9282671 [ dbSNP | Ensembl ].
VAR_028736
Natural variant1151A → P in GLC3A. Ref.34
VAR_054230
Natural variant1191A → S in allele CYP1B1*2, allele CYP1B1*6 and allele CYP1B1*7; significantly associated with breast or lung cancer; no significant change in 17beta-estradiol 2- and 4-hydroxylation activities and 17beta-estradiol affinity; 1.5-fold reduction in testosterone affinity but nearly no change in testosterone 6beta-hydroxylation activity; 2-fold increase in progesterone 6beta- and 16alpha-hydroxylation activities and 5-fold reduction in progesterone affinity. Ref.5 Ref.8 Ref.20 Ref.23 Ref.24 Ref.28 Ref.29 Ref.31 Ref.32 Ref.34 Ref.37
Corresponds to variant rs1056827 [ dbSNP | Ensembl ].
VAR_011753
Natural variant1321M → R in GLC3A. Ref.34
VAR_054231
Natural variant1441Q → H. Ref.39
VAR_054232
Natural variant1441Q → P in GLC3A. Ref.34
VAR_054233
Natural variant1441Q → R in GLC3A. Ref.30
VAR_054234
Natural variant1451R → W in POAG. Ref.39
VAR_054235
Natural variant1841G → S. Ref.27
VAR_054236
Natural variant1891A → P Associated with ocular hypertension susceptibility. Ref.39
VAR_054237
Natural variant1921D → V in GLC3A. Ref.24
VAR_054238
Natural variant1931P → L in GLC3A. Ref.27 Ref.34
VAR_054239
Natural variant1981V → I in GLC3A. Ref.24
Corresponds to variant rs59472972 [ dbSNP | Ensembl ].
VAR_054240
Natural variant2031N → S in GLC3A; reduces enzymatic activity. Ref.40
VAR_054241
Natural variant2061S → N. Ref.5
Corresponds to variant rs9341248 [ dbSNP | Ensembl ].
VAR_018869
Natural variant2151S → I in GLC3A. Ref.32
VAR_054242
Natural variant2291E → K in GLC3A and POAG; juvenile-onset; hypomorphic allele; reduces the abundance of the enzyme. Ref.27 Ref.31 Ref.33 Ref.34 Ref.37 Ref.38 Ref.39 Ref.40
Corresponds to variant rs57865060 [ dbSNP | Ensembl ].
VAR_054243
Natural variant2321G → R in GLC3A and POAG; adult-onset. Ref.31 Ref.33
VAR_054244
Natural variant2391S → R in GLC3A. Ref.34
VAR_054245
Natural variant2661R → L. Ref.5
Corresponds to variant rs9341250 [ dbSNP | Ensembl ].
VAR_018870
Natural variant269 – 2713Missing in GLC3A and POAG.
VAR_054246
Natural variant3201V → L in GLC3A. Ref.24
VAR_054247
Natural variant3301A → F in GLC3A; requires 2 nucleotide substitutions; unknown pathological significance. Ref.24
VAR_054248
Natural variant3301A → S Associated with ocular hypertension susceptibility. Ref.39
VAR_054249
Natural variant3431Missing in GLC3A; reduces enzymatic activity and also the abundance of the enzyme. Ref.38 Ref.40
VAR_054250
Natural variant3451L → F in POAG. Ref.26
VAR_054251
Natural variant355 – 3584Missing in GLC3A.
VAR_054252
Natural variant3641V → M in GLC3A. Ref.22 Ref.24 Ref.32
VAR_054253
Natural variant3651G → W in GLC3A; allele CYP1B1*18. Ref.16
Corresponds to variant rs55771538 [ dbSNP | Ensembl ].
VAR_001245
Natural variant3681R → H in GLC3A and GLC1A; acts as GLC1A disease modifier in patients also carrying Val-399 mutation in MYOC. Ref.20 Ref.26 Ref.27 Ref.28 Ref.34 Ref.36 Ref.37 Ref.38
Corresponds to variant rs28936414 [ dbSNP | Ensembl ].
VAR_016034
Natural variant3741D → N in GLC3A. Ref.15 Ref.20
Corresponds to variant rs28936413 [ dbSNP | Ensembl ].
VAR_001246
Natural variant3791P → L in allele CYP1B1*19. Ref.16
Corresponds to variant rs56305281 [ dbSNP | Ensembl ].
VAR_008351
Natural variant3871E → K in GLC3A and POAG; allele CYP1B1*20. Ref.16 Ref.19 Ref.28 Ref.31 Ref.33 Ref.38
Corresponds to variant rs55989760 [ dbSNP | Ensembl ].
VAR_008352
Natural variant3881A → T in GLC3A. Ref.36
VAR_054254
Natural variant3901R → C in GLC3A. Ref.34 Ref.35
VAR_054255
Natural variant3901R → H in GLC3A; allele CYP1B1*21. Ref.16 Ref.33 Ref.34
Corresponds to variant rs56010818 [ dbSNP | Ensembl ].
VAR_008353
Natural variant3901R → S in GLC3A. Ref.20 Ref.31
VAR_054256
Natural variant3991I → S in GLC3A. Ref.31
VAR_054257
Natural variant4091V → F in POAG. Ref.39
VAR_054258
Natural variant4221V → G. Ref.36
VAR_054259
Natural variant4231N → Y in GLC3A and POAG; juvenile-onset. Ref.31 Ref.33
VAR_054260
Natural variant4321L → V in allele CYP1B1*3, allele CYP1B1*5, allele CYP1B1*6 and allele CYP1B1*7; 1.6-fold increase in 17beta-estradiol 4-hydroxylation activity but no change in 17beta-estradiol 2-hydroxylation activity; 2-fold reduction in testosterone 6beta-hydroxylation activity and 3-fold reduction in testosterone affinity; 6-fold and 4-fold increase in progesterone 6beta- and 16alpha-hydroxylation activity, respectively and 7-fold reduction in progesterone affinity. Ref.5 Ref.8 Ref.16 Ref.17 Ref.20 Ref.23 Ref.24 Ref.26 Ref.27 Ref.28 Ref.29 Ref.31 Ref.32 Ref.33 Ref.34 Ref.37
Corresponds to variant rs1056836 [ dbSNP | Ensembl ].
VAR_001248
Natural variant4371P → L in GLC3A; allele CYP1B1*23. Ref.16 Ref.28 Ref.34
Corresponds to variant rs56175199 [ dbSNP | Ensembl ].
VAR_008354
Natural variant4411D → H.
Corresponds to variant rs4986887 [ dbSNP | Ensembl ].
VAR_028737
Natural variant4431A → G in GLC3A and POAG; allele CYP1B1*7; unknown pathological significance. Ref.28 Ref.29 Ref.33 Ref.39
Corresponds to variant rs4986888 [ dbSNP | Ensembl ].
VAR_018774
Natural variant4441R → Q in GLC3A. Ref.24
VAR_054261
Natural variant4451F → C in GLC3A. Ref.30
VAR_054262
Natural variant4491D → E.
Corresponds to variant rs1056837 [ dbSNP | Ensembl ].
VAR_028738
Natural variant4531N → S in allele CYP1B1*4. Ref.4 Ref.5 Ref.17 Ref.20 Ref.28 Ref.29 Ref.31 Ref.32 Ref.33 Ref.34 Ref.37
Corresponds to variant rs1800440 [ dbSNP | Ensembl ].
VAR_008355
Natural variant4661G → D in GLC3A. Ref.34
VAR_054263
Natural variant4691R → W in GLC3A; allele CYP1B1*25. Ref.15 Ref.16 Ref.20 Ref.38
Corresponds to variant rs28936701 [ dbSNP | Ensembl ].
VAR_001247
Natural variant4991E → G in GLC3A. Ref.24
VAR_054264
Natural variant5151S → L in POAG; unknown pathological significance. Ref.37
VAR_054265
Natural variant5181V → A. Ref.37
VAR_054266
Natural variant5231R → T in POAG; juvenile-onset. Ref.37
VAR_054267
Natural variant5301D → G in POAG. Ref.37
VAR_054268

Experimental info

Mutagenesis3951V → L: Invertes the 4OH E2:2OH E2 hydroxylation preference from 5.1 to 0.45. Ref.12

Secondary structure

................................................................. 543
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q16678 [UniParc].

Last modified June 7, 2004. Version 2.
Checksum: 46B6DA7368F63EA2

FASTA54360,846
        10         20         30         40         50         60 
MGTSLSPNDP WPLNPLSIQQ TTLLLLLSVL ATVHVGQRLL RQRRRQLRSA PPGPFAWPLI 

        70         80         90        100        110        120 
GNAAAVGQAA HLSFARLARR YGDVFQIRLG SCPIVVLNGE RAIHQALVQQ GSAFADRPAF 

       130        140        150        160        170        180 
ASFRVVSGGR SMAFGHYSEH WKVQRRAAHS MMRNFFTRQP RSRQVLEGHV LSEARELVAL 

       190        200        210        220        230        240 
LVRGSADGAF LDPRPLTVVA VANVMSAVCF GCRYSHDDPE FRELLSHNEE FGRTVGAGSL 

       250        260        270        280        290        300 
VDVMPWLQYF PNPVRTVFRE FEQLNRNFSN FILDKFLRHC ESLRPGAAPR DMMDAFILSA 

       310        320        330        340        350        360 
EKKAAGDSHG GGARLDLENV PATITDIFGA SQDTLSTALQ WLLLLFTRYP DVQTRVQAEL 

       370        380        390        400        410        420 
DQVVGRDRLP CMGDQPNLPY VLAFLYEAMR FSSFVPVTIP HATTANTSVL GYHIPKDTVV 

       430        440        450        460        470        480 
FVNQWSVNHD PLKWPNPENF DPARFLDKDG LINKDLTSRV MIFSVGKRRC IGEELSKMQL 

       490        500        510        520        530        540 
FLFISILAHQ CDFRANPNEP AKMNFSYGLT IKPKSFKVNV TLRESMELLD SAVQNLQAKE 


TCQ 

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References

« Hide 'large scale' references
[1]"Complete cDNA sequence of a human dioxin-inducible mRNA identifies a new gene subfamily of cytochrome P450 that maps to chromosome 2."
Sutter T.R., Tang Y.M., Hayes C.L., Wo Y.-Y.P., Jabs E.W., Li X., Yin H., Cody C.W., Greenlee W.F.
J. Biol. Chem. 269:13092-13099(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INDUCTION.
[2]"Isolation and characterization of the human cytochrome P450 CYP1B1 gene."
Tang Y.M., Wo Y.-Y.P., Stewart J., Hawkins A.L., Griffin C.A., Sutter T.R., Greenlee W.F.
J. Biol. Chem. 271:28324-28330(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"Physical/genetic map of the 2p22-2p21 region on chromosome 2."
Gorry M.C., Zhang Y., Marks J.J., Suppe B., Hart P.S., Cortelli J.R., Pallos D., Hart T.C.
Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT SER-453.
[5]NIEHS SNPs program
Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS GLY-48; SER-119; ASN-206; LEU-266; VAL-432 AND SER-453.
[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].
Tissue: Lung.
[7]Guillemette C.
Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-112, VARIANT GLY-48.
[8]"Catalytic properties of polymorphic human cytochrome P450 1B1 variants."
Shimada T., Watanabe J., Kawajiri K., Sutter T.R., Guengerich F.P., Gillam E.M.J., Inoue K.
Carcinogenesis 20:1607-1613(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, CHARACTERIZATION OF VARIANTS SER-119 AND VAL-432.
[9]"Phenotypic heterogeneity of CYP1B1: mutations in a patient with Peters' anomaly."
Vincent A., Billingsley G., Priston M., Williams-Lyn D., Sutherland J., Glaser T., Oliver E., Walter M.A., Heathcote G., Levin A., Heon E.
J. Med. Genet. 38:324-326(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: INVOLVEMENT IN PETAN.
[10]"Metabolism of retinoids and arachidonic acid by human and mouse cytochrome P450 1b1."
Choudhary D., Jansson I., Stoilov I., Sarfarazi M., Schenkman J.B.
Drug Metab. Dispos. 32:840-847(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES.
[11]"Increase of human CYP1B1 activities by acidic phospholipids and kinetic deuterium isotope effects on CYP1B1 substrate oxidation."
Jang H.H., Kim S.Y., Kang J.Y., Park S.H., Ryu S.H., Ahn T., Yun C.H.
J. Biochem. 152:433-442(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, ENZYME REGULATION, FUNCTION.
[12]"Specificity determinants of CYP1B1 estradiol hydroxylation."
Nishida C.R., Everett S., Ortiz de Montellano P.R.
Mol. Pharmacol. 84:451-458(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF VAL-395, FUNCTION IN ESTROGEN METABOLISM.
[13]"The citrus flavanone naringenin suppresses CYP1B1 transactivation through antagonising xenobiotic-responsive element binding."
Poon C.H., Wong T.Y., Wang Y., Tsuchiya Y., Nakajima M., Yokoi T., Leung L.K.
Br. J. Nutr. 109:1598-1605(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION.
[14]"Structural characterization of the complex between alpha-naphthoflavone and human cytochrome P450 1B1."
Wang A., Savas U., Stout C.D., Johnson E.F.
J. Biol. Chem. 286:5736-5743(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS) OF 51-543 IN COMPLEX WITH HEME AND THE INHIBITOR ALPHA-NAPHTOFLAVONE, COFACTOR.
[15]"Mutations in CYP1B1, the gene for cytochrome P4501B1, are the predominant cause of primary congenital glaucoma in Saudi Arabia."
Bejjani B.A., Lewis R.A., Tomey K.F., Anderson K.L., Dueker D.K., Jabak M., Astle W.F., Otterud B., Leppert M., Lupski J.R.
Am. J. Hum. Genet. 62:325-333(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLC3A GLU-61; ASN-374 AND TRP-469.
[16]"Sequence analysis and homology modeling suggest that primary congenital glaucoma on 2p21 results from mutations disrupting either the hinge region or the conserved core structures of cytochrome P4501B1."
Stoilov I., Akarsu A.N., Alozie I., Child A., Barsoum-Homsy M., Turacli M.E., Or M., Lewis R.A., Ozdemir N., Brice G., Aktan S.G., Chevrette L., Coca-Prados M., Sarfarazi M.
Am. J. Hum. Genet. 62:573-584(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLC3A TRP-365, VARIANTS CYS-57; GLU-61; TRP-365; LEU-379; LYS-387; HIS-390; VAL-432; LEU-437 AND TRP-469.
[17]"Association of cytochrome P450 1B1 (CYP1B1) polymorphism with steroid receptor status in breast cancer."
Bailey L.R., Roodi N., Dupont W.D., Parl F.F.
Cancer Res. 58:5038-5041(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS VAL-432 AND SER-453.
[18]Erratum
Bailey L.R., Roodi N., Dupont W.D., Parl F.F.
Cancer Res. 59:1388-1388(1999)
[19]"Identification of a single ancestral CYP1B1 mutation in Slovak Gypsies (Roms) affected with primary congenital glaucoma."
Plasilova M., Stoilov I., Sarfarazi M., Kadasi L., Ferakova E., Ferak V.
J. Med. Genet. 36:290-294(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLC3A LYS-387.
[20]"Multiple CYP1B1 mutations and incomplete penetrance in an inbred population segregating primary congenital glaucoma suggest frequent de novo events and a dominant modifier locus."
Bejjani B.A., Stockton D.W., Lewis R.A., Tomey K.F., Dueker D.K., Jabak M., Astle W.F., Lupski J.R.
Hum. Mol. Genet. 9:367-374(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLC3A GLU-61; PRO-77; 269-SER--PHE-271 DEL; HIS-368; ASN-374; SER-390 AND TRP-469, VARIANTS GLY-48; SER-119; VAL-432 AND SER-453.
[21]Erratum
Bejjani B.A., Stockton D.W., Lewis R.A., Tomey K.F., Dueker D.K., Jabak M., Astle W.F., Lupski J.R.
Hum. Mol. Genet. 9:1141-1141(2000)
[22]"Novel compound heterozygous mutations in the cytochrome P4501B1 gene (CYP1B1) in a Japanese patient with primary congenital glaucoma."
Ohtake Y., Kubota R., Tanino T., Miyata H., Mashima Y.
Ophthalmic Genet. 21:191-193(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLC3A MET-364.
[23]"Association of CYP1B1 genetic polymorphism with incidence to breast and lung cancer."
Watanabe J., Shimada T., Gillam E.M., Ikuta T., Suemasu K., Higashi Y., Gotoh O., Kawajiri K.
Pharmacogenetics 10:25-33(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SER-119 AND VAL-432, ASSOCIATION WITH BREAST OR LUNG CANCER.
[24]"Novel cytochrome P4501B1 (CYP1B1) gene mutations in Japanese patients with primary congenital glaucoma."
Mashima Y., Suzuki Y., Sergeev Y., Ohtake Y., Tanino T., Kimura I., Miyata H., Aihara M., Tanihara H., Inatani M., Azuma N., Iwata T., Araie M.
Invest. Ophthalmol. Vis. Sci. 42:2211-2216(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLC3A VAL-192; ILE-198; LEU-320; PHE-330; MET-364; GLN-444 AND GLY-499, VARIANTS GLY-48; SER-119 AND VAL-432.
[25]Erratum
Mashima Y., Suzuki Y., Sergeev Y., Ohtake Y., Tanino T., Kimura I., Miyata H., Aihara M., Tanihara H., Inatani M., Azuma N., Iwata T., Araie M.
Invest. Ophthalmol. Vis. Sci. 42:2775-2775(2001)
[26]"Digenic inheritance of early-onset glaucoma: CYP1B1, a potential modifier gene."
Vincent A.L., Billingsley G., Buys Y., Levin A.V., Priston M., Trope G., Williams-Lyn D., Heon E.
Am. J. Hum. Genet. 70:448-460(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT POAG PHE-345, VARIANT GLC1A HIS-368, VARIANT VAL-432.
[27]"Identification of novel mutations causing familial primary congenital glaucoma in Indian pedigrees."
Panicker S.G., Reddy A.B.M., Mandal A.K., Ahmed N., Nagarajaram H.A., Hasnain S.E., Balasubramanian D.
Invest. Ophthalmol. Vis. Sci. 43:1358-1366(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLC3A GLU-61; LEU-193; LYS-229 AND HIS-368, VARIANTS GLY-48; SER-184 AND VAL-432.
[28]"Molecular genetics of primary congenital glaucoma in Brazil."
Stoilov I.R., Costa V.P., Vasconcellos J.P.C., Melo M.B., Betinjane A.J., Carani J.C.E., Oltrogge E.V., Sarfarazi M.
Invest. Ophthalmol. Vis. Sci. 43:1820-1827(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLC3A HIS-368; LYS-387; LEU-437 AND GLY-443, VARIANTS GLY-48; SER-119; VAL-432 AND SER-453.
[29]"Functional analysis of six different polymorphic CYP1B1 enzyme variants found in an Ethiopian population."
Aklillu E., Oscarson M., Hidestrand M., Leidvik B., Otter C., Ingelman-Sundberg M.
Mol. Pharmacol. 61:586-594(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLY-48; SER-119; VAL-432; GLY-443 AND SER-453.
[30]"Gene symbol: CYP1B1. Disease: glaucoma, primary congenital."
Chakrabarti S., Komatireddy S., Mandal A.K., Balasubramanian D.
Hum. Genet. 113:556-558(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLC3A ARG-144 AND CYS-445.
[31]"Novel cytochrome P450 1B1 (CYP1B1) mutations in patients with primary congenital glaucoma in France."
Colomb E., Kaplan J., Garchon H.-J.
Hum. Mutat. 22:496-496(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLC3A LYS-229; ARG-232; LYS-387; SER-390; SER-399 AND TYR-423, VARIANTS GLY-48; SER-119; VAL-432 AND SER-453.
[32]"CYP1B1 gene analysis in primary congenital glaucoma in Indonesian and European patients."
Sitorus R., Ardjo S.M., Lorenz B., Preising M.
J. Med. Genet. 40:E9-E9(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLC3A ILE-215; 355-ARG--ALA-358 DEL AND MET-364, VARIANTS GLY-48; SER-119; VAL-432 AND SER-453.
[33]"CYP1B1 mutations in French patients with early-onset primary open-angle glaucoma."
Melki R., Colomb E., Lefort N., Brezin A.P., Garchon H.-J.
J. Med. Genet. 41:647-651(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS POAG ASN-81; LYS-229; ARG-232; SER-269--PHE-271 DEL; LYS-387; HIS-390; TYR-423 AND GLY-443, VARIANTS GLC3A ARG-232; LYS-387 AND TYR-423, VARIANTS GLY-48; SER119; VAL-432 AND SER-453.
[34]"Mutation spectrum of the CYP1B1 gene in Indian primary congenital glaucoma patients."
Reddy A.B.M., Kaur K., Mandal A.K., Panicker S.G., Thomas R., Hasnain S.E., Balasubramanian D., Chakrabarti S.
Mol. Vis. 10:696-702(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLC3A PRO-77; PRO-115; ARG-132; PRO-144; LEU-193; LYS-229; ARG-239; HIS-368; HIS-390; CYS-390; LEU-437 AND ASP-466, VARIANTS GLY-48; SER-119; VAL-432 AND SER-453.
[35]"Cytochrome P4501B1 mutations cause only part of primary congenital glaucoma in Ecuador."
Curry S.M., Daou A.G., Hermanns P., Molinari A., Lewis R.A., Bejjani B.A.
Ophthalmic Genet. 25:3-9(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GLC3A CYS-390.
[36]"Molecular and clinical evaluation of primary congenital glaucoma in Kuwait."
Alfadhli S., Behbehani A., Elshafey A., Abdelmoaty S., Al-Awadi S.
Am. J. Ophthalmol. 141:512-516(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLC3A GLU-61; HIS-368 AND THR-388, VARIANT GLY-422.
[37]"Primary role of CYP1B1 in Indian juvenile-onset POAG patients."
Acharya M., Mookherjee S., Bhattacharjee A., Bandyopadhyay A.K., Daulat Thakur S.K., Bhaduri G., Sen A., Ray K.
Mol. Vis. 12:399-404(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS POAG CYS-57; LYS-229; HIS-368; LEU-515; THR-523 AND GLY-530, VARIANTS GLY-48; SER-119; VAL-432; SER-453 AND ALA-518.
[38]"Primary congenital glaucoma and Rieger's anomaly: extended haplotypes reveal founder effects for eight distinct CYP1B1 mutations."
Chavarria-Soley G., Michels-Rautenstrauss K., Pasutto F., Flikier D., Flikier P., Cirak S., Bejjani B., Winters D.L., Lewis R.A., Mardin C., Reis A., Rautenstrauss B.
Mol. Vis. 12:523-531(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GLC3A GLU-61; ASN-81; LYS-229; LEU-343 DEL; HIS-368; LYS-387 AND TRP-469.
[39]"Heterozygous CYP1B1 gene mutations in Spanish patients with primary open-angle glaucoma."
Lopez-Garrido M.-P., Sanchez-Sanchez F., Lopez-Martinez F., Aroca-Aguilar J.-D., Blanco-Marchite C., Coca-Prados M., Escribano J.
Mol. Vis. 12:748-755(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS POAG TRP-28; GLU-61; ASN-81; TRP-145; LYS-229; PHE-409 AND GLY-443, VARIANTS LEU-52; HIS-144; PRO-189 AND SER-330.
[40]"Mutations in CYP1B1 cause primary congenital glaucoma by reduction of either activity or abundance of the enzyme."
Chavarria-Soley G., Sticht H., Aklillu E., Ingelman-Sundberg M., Pasutto F., Reis A., Rautenstrauss B.
Hum. Mutat. 29:1147-1153(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: CHARACTERIZATION OF VARIANTS GLC3A GLU-61; SER-203; LYS-229 AND LEU-343 DEL, CHARACTERIZATION OF VARIANT POAG ASN-81.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U03688 mRNA. Translation: AAA19567.1.
U56438 Genomic DNA. Translation: AAC50809.1.
AF450132, AF450131 Genomic DNA. Translation: AAM50512.1.
BT019979 mRNA. Translation: AAV38782.1.
AY393998 Genomic DNA. Translation: AAQ87875.1.
BC012049 mRNA. Translation: AAH12049.1.
AF171066 Genomic DNA. Translation: AAG43404.1.
CCDSCCDS1793.1.
PIRA54116.
RefSeqNP_000095.2. NM_000104.3.
UniGeneHs.154654.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3PM0X-ray2.70A51-543[»]
ProteinModelPortalQ16678.
SMRQ16678. Positions 68-530.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid107925. 2 interactions.
IntActQ16678. 1 interaction.
STRING9606.ENSP00000260630.

Chemistry

BindingDBQ16678.
ChEMBLCHEMBL4878.
DrugBankDB00655. Estrone.

PTM databases

PhosphoSiteQ16678.

Polymorphism databases

DMDM48429256.

Proteomic databases

MaxQBQ16678.
PaxDbQ16678.
PRIDEQ16678.

Protocols and materials databases

DNASU1545.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000260630; ENSP00000260630; ENSG00000138061.
ENST00000407341; ENSP00000384972; ENSG00000138061.
GeneID1545.
KEGGhsa:1545.
UCSCuc002rqo.2. human.

Organism-specific databases

CTD1545.
GeneCardsGC02M038206.
GeneReviewsCYP1B1.
H-InvDBHIX0001979.
HGNCHGNC:2597. CYP1B1.
HPACAB011705.
HPA026863.
MIM137750. phenotype.
137760. phenotype.
231300. phenotype.
601771. gene.
604229. phenotype.
neXtProtNX_Q16678.
Orphanet98976. Congenital glaucoma.
98977. Juvenile glaucoma.
708. Peters anomaly.
353225. Primary adult open-angle glaucoma.
PharmGKBPA27094.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2124.
HOGENOMHOG000036991.
HOVERGENHBG106944.
InParanoidQ16678.
KOK07410.
OrthoDBEOG7RBZ85.
PhylomeDBQ16678.
TreeFamTF105095.

Enzyme and pathway databases

BioCycMetaCyc:HS06443-MONOMER.
ReactomeREACT_111217. Metabolism.
SABIO-RKQ16678.

Gene expression databases

ArrayExpressQ16678.
BgeeQ16678.
CleanExHS_CYP1B1.
GenevestigatorQ16678.

Family and domain databases

Gene3D1.10.630.10. 1 hit.
InterProIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
[Graphical view]
PfamPF00067. p450. 1 hit.
[Graphical view]
PRINTSPR00463. EP450I.
PR00385. P450.
SUPFAMSSF48264. SSF48264. 1 hit.
PROSITEPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ16678.
GeneWikiCYP1B1.
GenomeRNAi1545.
NextBio6395.
PROQ16678.
SOURCESearch...

Entry information

Entry nameCP1B1_HUMAN
AccessionPrimary (citable) accession number: Q16678
Secondary accession number(s): Q5TZW8, Q93089, Q9H316
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: June 7, 2004
Last modified: July 9, 2014
This is version 165 of the entry and version 2 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 2

Human chromosome 2: entries, gene names and cross-references to MIM