CP8B1_HUMAN
ID CP8B1_HUMAN Reviewed; 501 AA.
AC Q9UNU6; B2RCY3; O75958; Q6NWT2; Q6NWT3;
DT 21-FEB-2001, integrated into UniProtKB/Swiss-Prot.
DT 05-OCT-2010, sequence version 2.
DT 03-AUG-2022, entry version 171.
DE RecName: Full=7-alpha-hydroxycholest-4-en-3-one 12-alpha-hydroxylase;
DE EC=1.14.14.139 {ECO:0000269|PubMed:10051404};
DE AltName: Full=7-alpha-hydroxy-4-cholesten-3-one 12-alpha-hydroxylase;
DE AltName: Full=CYPVIIIB1;
DE AltName: Full=Cytochrome P450 8B1;
DE AltName: Full=Sterol 12-alpha-hydroxylase;
GN Name=CYP8B1 {ECO:0000303|PubMed:10051404, ECO:0000312|HGNC:HGNC:2653};
GN Synonyms=CYP12;
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 / MRNA], VARIANTS PRO-88 AND HIS-234,
RP FUNCTION, CATALYTIC ACTIVITY, AND TISSUE SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=10051404; DOI=10.1006/geno.1998.5606;
RA Gaafvels M., Olin M., Chowdhary B.P., Raudsepp T., Andersson U.,
RA Persson B., Jansson M., Bjoerkhem I., Eggertsen G.;
RT "Structure and chromosomal assignment of the sterol 12alpha-hydroxylase
RT gene (CYP8B1) in human and mouse: eukaryotic cytochrome P-450 gene devoid
RT of introns.";
RL Genomics 56:184-196(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-88.
RC TISSUE=Liver;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT PRO-88.
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 [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-326, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in primary bile acid
CC biosynthesis. Catalyzes the 12alpha-hydroxylation of 7alpha-hydroxy-4-
CC cholesten-3-one, an intermediate metabolite in cholic acid biosynthesis
CC (PubMed:10051404). Controls biliary balance of cholic acid and
CC chenodeoxycholic acid, ultimately regulating the intestinal absorption
CC of dietary lipids (By similarity). Mechanistically, uses molecular
CC oxygen inserting one oxygen atom into a substrate, and reducing the
CC second into a water molecule, with two electrons provided by NADPH via
CC cytochrome P450 reductase (CPR; NADPH--hemoprotein reductase) (By
CC similarity). {ECO:0000250|UniProtKB:O02766,
CC ECO:0000250|UniProtKB:O88962, ECO:0000269|PubMed:10051404}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=7alpha-hydroxycholest-4-en-3-one + O2 + reduced [NADPH--
CC hemoprotein reductase] = 7alpha,12alpha-dihydroxycholest-4-en-3-one +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:46752, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:17899, ChEBI:CHEBI:28477, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.139;
CC Evidence={ECO:0000269|PubMed:10051404};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46753;
CC Evidence={ECO:0000305|PubMed:10051404};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5beta-cholestane-3alpha,7alpha-diol + O2 + reduced [NADPH--
CC hemoprotein reductase] = 5beta-cholestane-3alpha,7alpha,12alpha-triol
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:15261, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:16496, ChEBI:CHEBI:28047, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.139;
CC Evidence={ECO:0000269|PubMed:10051404};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:15262;
CC Evidence={ECO:0000305|PubMed:10051404};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=chenodeoxycholate + O2 + reduced [NADPH--hemoprotein
CC reductase] = cholate + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:65700, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:29747, ChEBI:CHEBI:36234, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210; EC=1.14.14.139;
CC Evidence={ECO:0000269|PubMed:10051404};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:65701;
CC Evidence={ECO:0000305|PubMed:10051404};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:O02766};
CC -!- PATHWAY: Lipid metabolism; bile acid biosynthesis.
CC {ECO:0000250|UniProtKB:O88962}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:O02766}; Single-pass membrane protein
CC {ECO:0000255}. Microsome membrane {ECO:0000250|UniProtKB:O02766};
CC Single-pass membrane protein {ECO:0000255}.
CC -!- TISSUE SPECIFICITY: Liver. {ECO:0000269|PubMed:10051404}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AF090318; AAC63037.1; -; mRNA.
DR EMBL; AF090320; AAD19877.1; -; Genomic_DNA.
DR EMBL; AK315330; BAG37730.1; -; mRNA.
DR EMBL; AC099329; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC067434; AAH67434.1; -; mRNA.
DR EMBL; BC067441; AAH67441.1; -; mRNA.
DR EMBL; BC067442; AAH67442.1; -; mRNA.
DR EMBL; BC067444; AAH67444.1; -; mRNA.
DR CCDS; CCDS2707.1; -.
DR RefSeq; NP_004382.2; NM_004391.2.
DR AlphaFoldDB; Q9UNU6; -.
DR SMR; Q9UNU6; -.
DR BioGRID; 107954; 11.
DR IntAct; Q9UNU6; 5.
DR STRING; 9606.ENSP00000318867; -.
DR ChEMBL; CHEMBL4523494; -.
DR SwissLipids; SLP:000001319; -.
DR iPTMnet; Q9UNU6; -.
DR PhosphoSitePlus; Q9UNU6; -.
DR BioMuta; CYP8B1; -.
DR DMDM; 308153428; -.
DR MassIVE; Q9UNU6; -.
DR PaxDb; Q9UNU6; -.
DR PeptideAtlas; Q9UNU6; -.
DR PRIDE; Q9UNU6; -.
DR ProteomicsDB; 85332; -.
DR Antibodypedia; 53027; 224 antibodies from 26 providers.
DR DNASU; 1582; -.
DR Ensembl; ENST00000316161.6; ENSP00000318867.4; ENSG00000180432.6.
DR GeneID; 1582; -.
DR KEGG; hsa:1582; -.
DR MANE-Select; ENST00000316161.6; ENSP00000318867.4; NM_004391.3; NP_004382.2.
DR UCSC; uc003cmh.4; human.
DR CTD; 1582; -.
DR DisGeNET; 1582; -.
DR GeneCards; CYP8B1; -.
DR HGNC; HGNC:2653; CYP8B1.
DR HPA; ENSG00000180432; Tissue enriched (liver).
DR MIM; 602172; gene.
DR neXtProt; NX_Q9UNU6; -.
DR OpenTargets; ENSG00000180432; -.
DR VEuPathDB; HostDB:ENSG00000180432; -.
DR eggNOG; KOG0684; Eukaryota.
DR GeneTree; ENSGT00940000153709; -.
DR HOGENOM; CLU_018012_1_3_1; -.
DR InParanoid; Q9UNU6; -.
DR OMA; WGFGTTQ; -.
DR OrthoDB; 572303at2759; -.
DR PhylomeDB; Q9UNU6; -.
DR TreeFam; TF105090; -.
DR PathwayCommons; Q9UNU6; -.
DR Reactome; R-HSA-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR Reactome; R-HSA-193775; Synthesis of bile acids and bile salts via 24-hydroxycholesterol.
DR Reactome; R-HSA-193807; Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
DR Reactome; R-HSA-197264; Nicotinamide salvaging.
DR Reactome; R-HSA-211979; Eicosanoids.
DR Reactome; R-HSA-211994; Sterols are 12-hydroxylated by CYP8B1.
DR Reactome; R-HSA-2162123; Synthesis of Prostaglandins (PG) and Thromboxanes (TX).
DR SignaLink; Q9UNU6; -.
DR UniPathway; UPA00221; -.
DR BioGRID-ORCS; 1582; 13 hits in 1066 CRISPR screens.
DR GeneWiki; CYP8B1; -.
DR GenomeRNAi; 1582; -.
DR Pharos; Q9UNU6; Tchem.
DR PRO; PR:Q9UNU6; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9UNU6; protein.
DR Bgee; ENSG00000180432; Expressed in right lobe of liver and 55 other tissues.
DR ExpressionAtlas; Q9UNU6; baseline and differential.
DR Genevisible; Q9UNU6; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0033779; F:5beta-cholestane-3alpha,7alpha-diol 12alpha-hydroxylase activity; IEA:UniProtKB-EC.
DR GO; GO:0033778; F:7alpha-hydroxycholest-4-en-3-one 12alpha-hydroxylase activity; TAS:Reactome.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0019825; F:oxygen binding; TAS:ProtInc.
DR GO; GO:0008397; F:sterol 12-alpha-hydroxylase activity; ISS:UniProtKB.
DR GO; GO:0006699; P:bile acid biosynthetic process; ISS:UniProtKB.
DR GO; GO:0038183; P:bile acid signaling pathway; IEA:Ensembl.
DR GO; GO:0045797; P:positive regulation of intestinal cholesterol absorption; ISS:UniProtKB.
DR GO; GO:0070723; P:response to cholesterol; IEA:Ensembl.
DR GO; GO:0031667; P:response to nutrient levels; IEA:Ensembl.
DR GO; GO:0016125; P:sterol metabolic process; TAS:Reactome.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR024204; Cyt_P450_CYP7A1-type.
DR InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR InterPro; IPR030686; Cytochrome_CYP8B1.
DR PANTHER; PTHR24306:SF0; PTHR24306:SF0; 1.
DR Pfam; PF00067; p450; 1.
DR PIRSF; PIRSF500627; Cytochrome_CYP8B1; 1.
DR PIRSF; PIRSF000047; Cytochrome_CYPVIIA1; 1.
DR PRINTS; PR00465; EP450IV.
DR SUPFAM; SSF48264; SSF48264; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Heme; Iron; Lipid biosynthesis; Lipid metabolism;
KW Membrane; Metal-binding; Microsome; Monooxygenase; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Steroid biosynthesis; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..501
FT /note="7-alpha-hydroxycholest-4-en-3-one 12-alpha-
FT hydroxylase"
FT /id="PRO_0000051913"
FT TRANSMEM 1..21
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 440
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"
FT MOD_RES 326
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:24275569"
FT VARIANT 88
FT /note="S -> P (in dbSNP:rs9865715)"
FT /evidence="ECO:0000269|PubMed:10051404,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:15489334"
FT /id="VAR_055102"
FT VARIANT 234
FT /note="R -> H (in dbSNP:rs199955644)"
FT /evidence="ECO:0000269|PubMed:10051404"
FT /id="VAR_010381"
FT VARIANT 238
FT /note="K -> R (in dbSNP:rs35764459)"
FT /id="VAR_055103"
FT VARIANT 357
FT /note="L -> F (in dbSNP:rs35637877)"
FT /id="VAR_055104"
FT CONFLICT 24
FT /note="M -> I (in Ref. 2; BAG37730)"
FT /evidence="ECO:0000305"
FT CONFLICT 60
FT /note="M -> V (in Ref. 4; AAH67444)"
FT /evidence="ECO:0000305"
FT CONFLICT 454
FT /note="I -> T (in Ref. 4; AAH67434/AAH67441)"
FT /evidence="ECO:0000305"
FT CONFLICT 468
FT /note="P -> L (in Ref. 4; AAH67444)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 501 AA; 58068 MW; 1B97698E8453E51A CRC64;
MVLWGPVLGA LLVVIAGYLC LPGMLRQRRP WEPPLDKGTV PWLGHAMAFR KNMFEFLKRM
RTKHGDVFTV QLGGQYFTFV MDPLSFGSIL KDTQRKLDFG QYAKKLVLKV FGYRSVQGDH
EMIHSASTKH LRGDGLKDLN ETMLDSLSFV MLTSKGWSLD ASCWHEDSLF RFCYYILFTA
GYLSLFGYTK DKEQDLLQAG ELFMEFRKFD LLFPRFVYSL LWPREWLEVG RLQRLFHKML
SVSHSQEKEG ISNWLGNMLQ FLREQGVPSA MQDKFNFMML WASQGNTGPT SFWALLYLLK
HPEAIRAVRE EATQVLGEAR LETKQSFAFK LGALQHTPVL DSVVEETLRL RAAPTLLRLV
HEDYTLKMSS GQEYLFRHGD ILALFPYLSV HMDPDIHPEP TVFKYDRFLN PNGSRKVDFF
KTGKKIHHYT MPWGSGVSIC PGRFFALSEV KLFILLMVTH FDLELVDPDT PLPHVDPQRW
GFGTMQPSHD VRFRYRLHPT E
