CP4B1_HUMAN
ID CP4B1_HUMAN Reviewed; 511 AA.
AC P13584; Q1HBI2; Q8TD85; Q8WWF2; Q8WWU9; Q8WWV0;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 07-JUN-2004, sequence version 2.
DT 03-AUG-2022, entry version 198.
DE RecName: Full=Cytochrome P450 4B1;
DE EC=1.14.14.1;
DE AltName: Full=CYPIVB1;
DE AltName: Full=Cytochrome P450-HP;
GN Name=CYP4B1;
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 [MRNA] (ISOFORM 1).
RC TISSUE=Lung;
RX PubMed=2574990; DOI=10.1021/bi00446a014;
RA Nhamburo P.T., Gonzalez F.J., McBride O.W., Gelboin H.V., Kimura S.;
RT "Identification of a new P450 expressed in human lung: complete cDNA
RT sequence, cDNA-directed expression, and chromosome mapping.";
RL Biochemistry 28:8060-8066(1989).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Placenta;
RX PubMed=2298205; DOI=10.1111/j.1432-1033.1990.tb15273.x;
RA Yokotani N., Sogawa K., Matsubara S., Gotoh O., Kusunose E., Kusunose M.,
RA Fujii-Kuriyama Y.;
RT "cDNA cloning of cytochrome P-450 related to P-450p-2 from the cDNA library
RT of human placenta. Gene structure and expression.";
RL Eur. J. Biochem. 187:23-29(1990).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS TRP-173; GLY-322;
RP ILE-331; CYS-340 AND CYS-375.
RX PubMed=12142726; DOI=10.1097/00008571-200207000-00004;
RA Lo-Guidice J.-M., Allorge D., Cauffiez C., Chevalier D., Lafitte J.-J.,
RA Lhermitte M., Broly F.;
RT "Genetic polymorphism of the human cytochrome P450 CYP4B1: evidence for a
RT non-functional allelic variant.";
RL Pharmacogenetics 12:367-374(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC TISSUE=Lung;
RX PubMed=12695542; DOI=10.1124/mol.63.5.1137;
RA Carr B.A., Ramakanth S., Dannan G.A., Yost G.S.;
RT "Characterization of pulmonary CYP4B2, specific catalyst of methyl
RT oxidation of 3-methylindole.";
RL Mol. Pharmacol. 63:1137-1147(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-111; TRP-173; TRP-264;
RP GLN-274; GLY-322; SER-329; ILE-331; CYS-340; CYS-354; CYS-375 AND GLN-482.
RG NIEHS SNPs program;
RL Submitted (APR-2006) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Lung;
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).
CC -!- FUNCTION: Cytochromes P450 are a group of heme-thiolate monooxygenases.
CC In liver microsomes, this enzyme is involved in an NADPH-dependent
CC electron transport pathway. It oxidizes a variety of structurally
CC unrelated compounds, including steroids, fatty acids, and xenobiotics.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an organic molecule + O2 + reduced [NADPH--hemoprotein
CC reductase] = an alcohol + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:17149, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:30879, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:142491; EC=1.14.14.1;
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P51869};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC membrane protein. Microsome membrane; Peripheral membrane protein.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P13584-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P13584-2; Sequence=VSP_038419;
CC -!- TISSUE SPECIFICITY: Detected in the liver and lung (at protein level).
CC {ECO:0000269|PubMed:12695542}.
CC -!- INDUCTION: P450 can be induced to high levels in liver and other
CC tissues by various foreign compounds, including drugs, pesticides, and
CC carcinogens.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=PharmVar Pharmacogen Variation Consortium;
CC Note=CYP4B1 alleles;
CC URL="https://www.pharmvar.org/gene/CYP4B1";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/cyp4b1/";
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CYP4B1ID40253ch1p33.html";
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DR EMBL; J02871; AAA35712.1; -; mRNA.
DR EMBL; X16699; CAA34672.1; -; mRNA.
DR EMBL; AF491285; AAM09532.1; -; mRNA.
DR EMBL; AY064485; AAL57720.1; -; mRNA.
DR EMBL; AY064486; AAL57721.1; -; mRNA.
DR EMBL; AY151048; AAN72311.1; -; mRNA.
DR EMBL; DQ518907; ABF47106.1; -; Genomic_DNA.
DR EMBL; AL593856; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL356793; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC017758; AAH17758.1; -; mRNA.
DR CCDS; CCDS41328.1; -. [P13584-2]
DR CCDS; CCDS542.1; -. [P13584-1]
DR PIR; S07765; O4HUB1.
DR RefSeq; NP_000770.2; NM_000779.3. [P13584-1]
DR RefSeq; NP_001093242.1; NM_001099772.1. [P13584-2]
DR AlphaFoldDB; P13584; -.
DR SMR; P13584; -.
DR BioGRID; 107952; 5.
DR IntAct; P13584; 1.
DR STRING; 9606.ENSP00000360991; -.
DR BindingDB; P13584; -.
DR ChEMBL; CHEMBL4523986; -.
DR DrugBank; DB01174; Phenobarbital.
DR DrugBank; DB00152; Thiamine.
DR iPTMnet; P13584; -.
DR PhosphoSitePlus; P13584; -.
DR BioMuta; CYP4B1; -.
DR DMDM; 48429213; -.
DR EPD; P13584; -.
DR MassIVE; P13584; -.
DR PaxDb; P13584; -.
DR PeptideAtlas; P13584; -.
DR PRIDE; P13584; -.
DR ProteomicsDB; 52929; -. [P13584-1]
DR ProteomicsDB; 52930; -. [P13584-2]
DR Antibodypedia; 981; 166 antibodies from 29 providers.
DR DNASU; 1580; -.
DR Ensembl; ENST00000271153.8; ENSP00000271153.4; ENSG00000142973.15. [P13584-1]
DR Ensembl; ENST00000371923.9; ENSP00000360991.4; ENSG00000142973.15. [P13584-2]
DR GeneID; 1580; -.
DR KEGG; hsa:1580; -.
DR MANE-Select; ENST00000371923.9; ENSP00000360991.4; NM_001099772.2; NP_001093242.1. [P13584-2]
DR UCSC; uc001cqm.5; human. [P13584-1]
DR CTD; 1580; -.
DR DisGeNET; 1580; -.
DR GeneCards; CYP4B1; -.
DR HGNC; HGNC:2644; CYP4B1.
DR HPA; ENSG00000142973; Tissue enhanced (lung).
DR MIM; 124075; gene.
DR neXtProt; NX_P13584; -.
DR OpenTargets; ENSG00000142973; -.
DR PharmGKB; PA27119; -.
DR VEuPathDB; HostDB:ENSG00000142973; -.
DR eggNOG; KOG0157; Eukaryota.
DR GeneTree; ENSGT00940000161441; -.
DR InParanoid; P13584; -.
DR OMA; LFGHAQE; -.
DR OrthoDB; 1247045at2759; -.
DR PhylomeDB; P13584; -.
DR TreeFam; TF105088; -.
DR PathwayCommons; P13584; -.
DR Reactome; R-HSA-211935; Fatty acids.
DR Reactome; R-HSA-211958; Miscellaneous substrates.
DR Reactome; R-HSA-211979; Eicosanoids.
DR Reactome; R-HSA-2142691; Synthesis of Leukotrienes (LT) and Eoxins (EX).
DR SignaLink; P13584; -.
DR BioGRID-ORCS; 1580; 34 hits in 1068 CRISPR screens.
DR ChiTaRS; CYP4B1; human.
DR GeneWiki; CYP4B1; -.
DR GenomeRNAi; 1580; -.
DR Pharos; P13584; Tbio.
DR PRO; PR:P13584; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; P13584; protein.
DR Bgee; ENSG00000142973; Expressed in bronchial epithelial cell and 158 other tissues.
DR ExpressionAtlas; P13584; baseline and differential.
DR Genevisible; P13584; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0070330; F:aromatase activity; IEA:UniProtKB-EC.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; TAS:Reactome.
DR GO; GO:0019825; F:oxygen binding; TAS:ProtInc.
DR GO; GO:0018879; P:biphenyl metabolic process; IEA:Ensembl.
DR GO; GO:0006631; P:fatty acid metabolic process; TAS:Reactome.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Endoplasmic reticulum; Heme; Iron; Membrane;
KW Metal-binding; Microsome; Monooxygenase; Oxidoreductase; Phosphoprotein;
KW Reference proteome.
FT CHAIN 1..511
FT /note="Cytochrome P450 4B1"
FT /id="PRO_0000051819"
FT BINDING 315
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /note="covalent"
FT /evidence="ECO:0000250|UniProtKB:P51869"
FT BINDING 453
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:P51869"
FT MOD_RES 436
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P20816"
FT VAR_SEQ 206
FT /note="H -> HS (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:12695542,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_038419"
FT VARIANT 111
FT /note="A -> V (in dbSNP:rs45559437)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_055377"
FT VARIANT 173
FT /note="R -> W (in allele CYP4B1*3 and allele CYP4B1*6;
FT dbSNP:rs4646487)"
FT /evidence="ECO:0000269|PubMed:12142726, ECO:0000269|Ref.5"
FT /id="VAR_018357"
FT VARIANT 264
FT /note="R -> W (in dbSNP:rs45446505)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_048453"
FT VARIANT 274
FT /note="R -> Q (in dbSNP:rs45578838)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_055378"
FT VARIANT 322
FT /note="S -> G (in allele CYP4B1*4; dbSNP:rs45467195)"
FT /evidence="ECO:0000269|PubMed:12142726, ECO:0000269|Ref.5"
FT /id="VAR_018358"
FT VARIANT 329
FT /note="Y -> S (in dbSNP:rs12094024)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_048454"
FT VARIANT 331
FT /note="M -> I (in allele CYP4B1*2, allele CYP4B1*7 and
FT allele CYP4B1*5; dbSNP:rs2297810)"
FT /evidence="ECO:0000269|PubMed:12142726, ECO:0000269|Ref.5"
FT /id="VAR_018359"
FT VARIANT 340
FT /note="R -> C (in allele CYP4B1*2 and allele CYP4B1*7;
FT dbSNP:rs4646491)"
FT /evidence="ECO:0000269|PubMed:12142726, ECO:0000269|Ref.5"
FT /id="VAR_018360"
FT VARIANT 345
FT /note="V -> I (in allele CYP4B1*6; dbSNP:rs1557501779)"
FT /id="VAR_018361"
FT VARIANT 354
FT /note="F -> C (in dbSNP:rs17102592)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_048455"
FT VARIANT 375
FT /note="R -> C (in allele CYP4B1*2; dbSNP:rs2297809)"
FT /evidence="ECO:0000269|PubMed:12142726, ECO:0000269|Ref.5"
FT /id="VAR_018362"
FT VARIANT 482
FT /note="R -> Q (in dbSNP:rs45622937)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_048456"
FT CONFLICT 37
FT /note="Q -> R (in Ref. 1; AAA35712)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 511 AA; 58991 MW; 91FED40949507EB8 CRC64;
MVPSFLSLSF SSLGLWASGL ILVLGFLKLI HLLLRRQTLA KAMDKFPGPP THWLFGHALE
IQETGSLDKV VSWAHQFPYA HPLWFGQFIG FLNIYEPDYA KAVYSRGDPK APDVYDFFLQ
WIGRGLLVLE GPKWLQHRKL LTPGFHYDVL KPYVAVFTES TRIMLDKWEE KAREGKSFDI
FCDVGHMALN TLMKCTFGRG DTGLGHRDSS YYLAVSDLTL LMQQRLVSFQ YHNDFIYWLT
PHGRRFLRAC QVAHDHTDQV IRERKAALQD EKVRKKIQNR RHLDFLDILL GARDEDDIKL
SDADLRAEVD TFMFEGHDTT TSGISWFLYC MALYPEHQHR CREEVREILG DQDFFQWDDL
GKMTYLTMCI KESFRLYPPV PQVYRQLSKP VTFVDGRSLP AGSLISMHIY ALHRNSAVWP
DPEVFDSLRF STENASKRHP FAFMPFSAGP RNCIGQQFAM SEMKVVTAMC LLRFEFSLDP
SRLPIKMPQL VLRSKNGFHL HLKPLGPGSG K
