ID CP7B1_HUMAN Reviewed; 506 AA.
AC O75881; B2RN07; Q9UNF5;
DT 15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT 11-FEB-2002, sequence version 2.
DT 24-JAN-2024, entry version 197.
DE RecName: Full=Cytochrome P450 7B1;
DE AltName: Full=24-hydroxycholesterol 7-alpha-hydroxylase {ECO:0000250|UniProtKB:Q60991};
DE EC=1.14.14.26 {ECO:0000250|UniProtKB:Q60991};
DE AltName: Full=25/26-hydroxycholesterol 7-alpha-hydroxylase {ECO:0000305|PubMed:10588945};
DE EC=1.14.14.29 {ECO:0000269|PubMed:10588945};
DE AltName: Full=3-hydroxysteroid 7-alpha hydroxylase {ECO:0000303|PubMed:24491228};
DE AltName: Full=Oxysterol 7-alpha-hydroxylase {ECO:0000303|PubMed:10588945};
GN Name=CYP7B1 {ECO:0000303|PubMed:24491228, ECO:0000312|HGNC:HGNC:2652};
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], INVOLVEMENT IN CBAS3, VARIANT HIS-324,
RP FUNCTION, CATALYTIC ACTIVITY, PATHWAY, AND SUBCELLULAR LOCATION.
RC TISSUE=Liver, and Spleen;
RX PubMed=9802883; DOI=10.1172/jci2962;
RA Setchell K.D.R., Schwarz M., O'Connell N.C., Lund E.G., Davis D.L.,
RA Lathe R., Thompson H.R., Tyson W.R., Sokol R.J., Russell D.W.;
RT "Identification of a new inborn error in bile acid synthesis: mutation of
RT the oxysterol 7-alpha-hydroxylase gene causes severe neonatal liver
RT disease.";
RL J. Clin. Invest. 102:1690-1703(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], FUNCTION, CATALYTIC ACTIVITY,
RP PATHWAY, AND TISSUE SPECIFICITY.
RC TISSUE=Hippocampus;
RX PubMed=10588945;
RA Wu Z.L., Martin K.O., Javitt N.B., Chiang J.Y.L.;
RT "Structure and functions of human oxysterol 7alpha-hydroxylase cDNAs and
RT gene CYP7B1.";
RL J. Lipid Res. 40:2195-2203(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND PATHWAY.
RX PubMed=24491228; DOI=10.1111/febs.12733;
RA Yantsevich A.V., Dichenko Y.V., Mackenzie F., Mukha D.V., Baranovsky A.V.,
RA Gilep A.A., Usanov S.A., Strushkevich N.V.;
RT "Human steroid and oxysterol 7alpha-hydroxylase CYP7B1: substrate
RT specificity, azole binding and misfolding of clinically relevant mutants.";
RL FEBS J. 281:1700-1713(2014).
RN [6]
RP IDENTIFICATION BY 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).
RN [7]
RP VARIANTS SPG5A ARG-57; SER-216; PHE-363 AND HIS-417.
RX PubMed=18252231; DOI=10.1016/j.ajhg.2007.10.001;
RA Tsaousidou M.K., Ouahchi K., Warner T.T., Yang Y., Simpson M.A.,
RA Laing N.G., Wilkinson P.A., Madrid R.E., Patel H., Hentati F., Patton M.A.,
RA Hentati A., Lamont P.J., Siddique T., Crosby A.H.;
RT "Sequence alterations within CYP7B1 implicate defective cholesterol
RT homeostasis in motor-neuron degeneration.";
RL Am. J. Hum. Genet. 82:510-515(2008).
RN [8]
RP VARIANTS SPG5A ALA-297; CYS-417; HIS-417; ILE-470 AND CYS-486, AND VARIANTS
RP PRO-19; TYR-106; SER-287 AND HIS-324.
RX PubMed=19439420; DOI=10.1093/brain/awp073;
RA Goizet C., Boukhris A., Durr A., Beetz C., Truchetto J., Tesson C.,
RA Tsaousidou M., Forlani S., Guyant-Marechal L., Fontaine B., Guimaraes J.,
RA Isidor B., Chazouilleres O., Wendum D., Grid D., Chevy F., Chinnery P.F.,
RA Coutinho P., Azulay J.P., Feki I., Mochel F., Wolf C., Mhiri C., Crosby A.,
RA Brice A., Stevanin G.;
RT "CYP7B1 mutations in pure and complex forms of hereditary spastic
RT paraplegia type 5.";
RL Brain 132:1589-1600(2009).
RN [9]
RP VARIANTS SPG5A VAL-87; LEU-285; ALA-297 AND ALA-443.
RX PubMed=21214876; DOI=10.1111/j.1399-0004.2011.01624.x;
RA Arnoldi A., Crimella C., Tenderini E., Martinuzzi A., D'Angelo M.G.,
RA Musumeci O., Toscano A., Scarlato M., Fantin M., Bresolin N., Bassi M.T.;
RT "Clinical phenotype variability in patients with hereditary spastic
RT paraplegia type 5 associated with CYP7B1 mutations.";
RL Clin. Genet. 81:150-157(2012).
RN [10]
RP VARIANTS SPG5A ASP-147; ALA-316 INS AND CYS-486.
RX PubMed=24117163; DOI=10.1111/ane.12188;
RA Roos P., Svenstrup K., Danielsen E.R., Thomsen C., Nielsen J.E.;
RT "CYP7B1: novel mutations and magnetic resonance spectroscopy abnormalities
RT in hereditary spastic paraplegia type 5A.";
RL Acta Neurol. Scand. 129:330-334(2014).
RN [11]
RP VARIANT SPG5A CYS-486.
RX PubMed=27217339; DOI=10.1093/brain/aww111;
RA Kara E., Tucci A., Manzoni C., Lynch D.S., Elpidorou M., Bettencourt C.,
RA Chelban V., Manole A., Hamed S.A., Haridy N.A., Federoff M., Preza E.,
RA Hughes D., Pittman A., Jaunmuktane Z., Brandner S., Xiromerisiou G.,
RA Wiethoff S., Schottlaender L., Proukakis C., Morris H., Warner T.,
RA Bhatia K.P., Korlipara L.V., Singleton A.B., Hardy J., Wood N.W.,
RA Lewis P.A., Houlden H.;
RT "Genetic and phenotypic characterization of complex hereditary spastic
RT paraplegia.";
RL Brain 139:1904-1918(2016).
RN [12]
RP VARIANT SPG5A ARG-198, AND VARIANT HIS-324.
RX PubMed=26714052; DOI=10.1016/j.mcp.2015.12.001;
RA Schubert S.F., Hoffjan S., Dekomien G.;
RT "Mutational analysis of the CYP7B1, PNPLA6 and C19orf12 genes in autosomal
RT recessive hereditary spastic paraplegia.";
RL Mol. Cell. Probes 30:53-55(2016).
CC -!- FUNCTION: A cytochrome P450 monooxygenase involved in the metabolism of
CC endogenous oxysterols and steroid hormones, including neurosteroids
CC (PubMed:10588945, PubMed:24491228). 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-ferrihemoprotein reductase)
CC (PubMed:10588945, PubMed:24491228). Catalyzes the hydroxylation of
CC carbon hydrogen bonds of steroids with a preference for 7-alpha
CC position (PubMed:10588945, PubMed:24491228). Usually metabolizes
CC steroids carrying a hydroxy group at position 3, functioning as a 3-
CC hydroxy steroid 7-alpha hydroxylase (PubMed:24491228). Hydroxylates
CC oxysterols, including 25-hydroxycholesterol and (25R)-cholest-5-ene-
CC 3beta,26-diol toward 7-alpha hydroxy derivatives, which may be
CC transported to the liver and converted to bile acids (PubMed:9802883,
CC PubMed:10588945). Via its product 7-alpha,25-dihydroxycholesterol, a
CC ligand for the chemotactic G protein-coupled receptor GPR183/EBI2,
CC regulates B cell migration in germinal centers of lymphoid organs, thus
CC guiding efficient maturation of plasma B cells and overall antigen-
CC specific humoral immune response (By similarity). 7-alpha hydroxylates
CC neurosteroids, including 3beta-hydroxyandrost-5-en-17-one
CC (dehydroepiandrosterone) and pregnenolone, both involved in
CC hippocampus-associated memory and learning (PubMed:24491228).
CC Metabolizes androstanoids toward 6- or 7-alpha hydroxy derivatives
CC (PubMed:24491228). {ECO:0000250|UniProtKB:Q60991,
CC ECO:0000269|PubMed:10588945, ECO:0000269|PubMed:24491228,
CC ECO:0000269|PubMed:9802883}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=25-hydroxycholesterol + O2 + reduced [NADPH--hemoprotein
CC reductase] = 7alpha,25-dihydroxycholesterol + H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:24308, Rhea:RHEA-
CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:37623,
CC ChEBI:CHEBI:42977, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC EC=1.14.14.29; Evidence={ECO:0000269|PubMed:10588945,
CC ECO:0000269|PubMed:9802883};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:24309;
CC Evidence={ECO:0000305|PubMed:10588945, ECO:0000305|PubMed:9802883};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(25R)-cholest-5-ene-3beta,26-diol + O2 + reduced [NADPH--
CC hemoprotein reductase] = (25R)-cholest-5-en-3beta,7alpha,26-triol +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:19041, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:76591,
CC ChEBI:CHEBI:76592; EC=1.14.14.29;
CC Evidence={ECO:0000269|PubMed:10588945};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:19042;
CC Evidence={ECO:0000305|PubMed:10588945};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(24S)-hydroxycholesterol + O2 + reduced [NADPH--hemoprotein
CC reductase] = (24S)-7alpha-dihydroxycholesterol + H(+) + H2O +
CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:46124,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:34310,
CC ChEBI:CHEBI:37640, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210;
CC EC=1.14.14.26; Evidence={ECO:0000250|UniProtKB:Q60991};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46125;
CC Evidence={ECO:0000250|UniProtKB:Q60991};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(24S)-25-epoxycholesterol + O2 + reduced [NADPH--hemoprotein
CC reductase] = (24S,25)-epoxy-7alpha-hydroxycholesterol + H(+) + H2O +
CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:46464,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:41633,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:86146;
CC Evidence={ECO:0000250|UniProtKB:Q60991};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46465;
CC Evidence={ECO:0000250|UniProtKB:Q60991};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(22R)-hydroxycholesterol + O2 + reduced [NADPH--hemoprotein
CC reductase] = (22R,7alpha)-dihydroxycholesterol + H(+) + H2O +
CC oxidized [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:46460,
CC Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:67237, ChEBI:CHEBI:86145;
CC Evidence={ECO:0000250|UniProtKB:Q60991};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46461;
CC Evidence={ECO:0000250|UniProtKB:Q60991};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=androst-5-en-3beta,17beta-diol + O2 + reduced [NADPH--
CC hemoprotein reductase] = androst-5-en-3beta,7alpha,17beta-triol +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:46204, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:2710, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:85810; Evidence={ECO:0000269|PubMed:24491228};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46205;
CC Evidence={ECO:0000305|PubMed:24491228};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=5alpha-androstane-3beta,17beta-diol + O2 + reduced [NADPH--
CC hemoprotein reductase] = 5alpha-androstane-3beta,6alpha,17beta-triol
CC + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:46200, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:18329, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:85809; Evidence={ECO:0000269|PubMed:24491228};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46201;
CC Evidence={ECO:0000305|PubMed:24491228};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta-hydroxyandrost-5-en-17-one + O2 + reduced [NADPH--
CC hemoprotein reductase] = 3beta,7alpha-dihydroxyandrost-5-en-17-one +
CC H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:46192, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:28689, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:81471; Evidence={ECO:0000269|PubMed:24491228};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46193;
CC Evidence={ECO:0000305|PubMed:24491228};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3beta-hydroxy-5alpha-androstan-17-one + O2 + reduced [NADPH--
CC hemoprotein reductase] = 3beta,7alpha-dihydroxy-5alpha-androstan-17-
CC one + H(+) + H2O + oxidized [NADPH--hemoprotein reductase];
CC Xref=Rhea:RHEA:43896, Rhea:RHEA-COMP:11964, Rhea:RHEA-COMP:11965,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:85816,
CC ChEBI:CHEBI:541975; Evidence={ECO:0000269|PubMed:24491228};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43897;
CC Evidence={ECO:0000305|PubMed:24491228};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=O2 + pregnenolone + reduced [NADPH--hemoprotein reductase] =
CC 7alpha-hydroxypregnenolone + H(+) + H2O + oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:46196, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16581, ChEBI:CHEBI:57618,
CC ChEBI:CHEBI:58210, ChEBI:CHEBI:81467;
CC Evidence={ECO:0000269|PubMed:24491228};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46197;
CC Evidence={ECO:0000305|PubMed:24491228};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P22680};
CC -!- ACTIVITY REGULATION: Inhibited by drugs voriconazole and metyrapone.
CC {ECO:0000269|PubMed:24491228}.
CC -!- PATHWAY: Lipid metabolism; bile acid biosynthesis.
CC {ECO:0000269|PubMed:10588945, ECO:0000269|PubMed:9802883}.
CC -!- PATHWAY: Steroid hormone biosynthesis. {ECO:0000269|PubMed:24491228}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000305|PubMed:9802883}; Multi-pass membrane protein
CC {ECO:0000305}. Microsome membrane {ECO:0000305|PubMed:9802883}; Multi-
CC pass membrane protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Expressed in brain, testis,
CC ovary, prostate, liver, colon, kidney, small intestine, thymus and
CC spleen. {ECO:0000269|PubMed:10588945}.
CC -!- DISEASE: Spastic paraplegia 5A, autosomal recessive (SPG5A)
CC [MIM:270800]: A form of spastic paraplegia, a neurodegenerative
CC disorder characterized by a slow, gradual, progressive weakness and
CC spasticity of the lower limbs. Rate of progression and the severity of
CC symptoms are quite variable. Initial symptoms may include difficulty
CC with balance, weakness and stiffness in the legs, muscle spasms, and
CC dragging the toes when walking. In some forms of the disorder, bladder
CC symptoms (such as incontinence) may appear, or the weakness and
CC stiffness may spread to other parts of the body.
CC {ECO:0000269|PubMed:18252231, ECO:0000269|PubMed:19439420,
CC ECO:0000269|PubMed:21214876, ECO:0000269|PubMed:24117163,
CC ECO:0000269|PubMed:26714052, ECO:0000269|PubMed:27217339}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Congenital bile acid synthesis defect 3 (CBAS3) [MIM:613812]:
CC A disorder resulting in severe cholestasis, cirrhosis and liver
CC synthetic failure. Hepatic microsomal oxysterol 7-alpha-hydroxylase
CC activity is undetectable. {ECO:0000269|PubMed:9802883}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="https://atlasgeneticsoncology.org/gene/40255/CYP7B1";
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DR EMBL; AF029403; AAC95426.1; -; mRNA.
DR EMBL; AF127090; AAD20021.1; -; mRNA.
DR EMBL; AF176805; AAK11850.1; -; Genomic_DNA.
DR EMBL; AF176800; AAK11850.1; JOINED; Genomic_DNA.
DR EMBL; AF176801; AAK11850.1; JOINED; Genomic_DNA.
DR EMBL; AF176802; AAK11850.1; JOINED; Genomic_DNA.
DR EMBL; AF176803; AAK11850.1; JOINED; Genomic_DNA.
DR EMBL; AF176804; AAK11850.1; JOINED; Genomic_DNA.
DR EMBL; CH471068; EAW86877.1; -; Genomic_DNA.
DR EMBL; BC136574; AAI36575.1; -; mRNA.
DR CCDS; CCDS6180.1; -.
DR RefSeq; NP_004811.1; NM_004820.4.
DR AlphaFoldDB; O75881; -.
DR SMR; O75881; -.
DR BioGRID; 114813; 5.
DR IntAct; O75881; 3.
DR STRING; 9606.ENSP00000310721; -.
DR DrugBank; DB01530; 5alpha-androstane-3alpha,17beta-diol.
DR SwissLipids; SLP:000001207; -.
DR iPTMnet; O75881; -.
DR PhosphoSitePlus; O75881; -.
DR BioMuta; CYP7B1; -.
DR jPOST; O75881; -.
DR MassIVE; O75881; -.
DR MaxQB; O75881; -.
DR PaxDb; 9606-ENSP00000310721; -.
DR PeptideAtlas; O75881; -.
DR ProteomicsDB; 50237; -.
DR Antibodypedia; 3058; 328 antibodies from 35 providers.
DR DNASU; 9420; -.
DR Ensembl; ENST00000310193.4; ENSP00000310721.3; ENSG00000172817.4.
DR GeneID; 9420; -.
DR KEGG; hsa:9420; -.
DR MANE-Select; ENST00000310193.4; ENSP00000310721.3; NM_004820.5; NP_004811.1.
DR UCSC; uc003xvj.3; human.
DR AGR; HGNC:2652; -.
DR CTD; 9420; -.
DR DisGeNET; 9420; -.
DR GeneCards; CYP7B1; -.
DR HGNC; HGNC:2652; CYP7B1.
DR HPA; ENSG00000172817; Tissue enhanced (liver).
DR MalaCards; CYP7B1; -.
DR MIM; 270800; phenotype.
DR MIM; 603711; gene.
DR MIM; 613812; phenotype.
DR neXtProt; NX_O75881; -.
DR OpenTargets; ENSG00000172817; -.
DR Orphanet; 100986; Autosomal recessive spastic paraplegia type 5A.
DR Orphanet; 79302; Congenital bile acid synthesis defect type 3.
DR PharmGKB; PA27124; -.
DR VEuPathDB; HostDB:ENSG00000172817; -.
DR eggNOG; KOG0684; Eukaryota.
DR GeneTree; ENSGT00940000153141; -.
DR HOGENOM; CLU_018012_1_2_1; -.
DR InParanoid; O75881; -.
DR OMA; WSEVVQM; -.
DR OrthoDB; 1537669at2759; -.
DR PhylomeDB; O75881; -.
DR TreeFam; TF105090; -.
DR BRENDA; 1.14.14.29; 2681.
DR PathwayCommons; O75881; -.
DR Reactome; R-HSA-192105; Synthesis of bile acids and bile salts.
DR Reactome; R-HSA-193368; Synthesis of bile acids and bile salts via 7alpha-hydroxycholesterol.
DR Reactome; R-HSA-193807; Synthesis of bile acids and bile salts via 27-hydroxycholesterol.
DR Reactome; R-HSA-211976; Endogenous sterols.
DR Reactome; R-HSA-5579013; Defective CYP7B1 causes SPG5A and CBAS3.
DR SignaLink; O75881; -.
DR SIGNOR; O75881; -.
DR UniPathway; UPA00221; -.
DR BioGRID-ORCS; 9420; 11 hits in 1151 CRISPR screens.
DR ChiTaRS; CYP7B1; human.
DR GeneWiki; CYP7B1; -.
DR GenomeRNAi; 9420; -.
DR Pharos; O75881; Tbio.
DR PRO; PR:O75881; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; O75881; Protein.
DR Bgee; ENSG00000172817; Expressed in seminal vesicle and 163 other cell types or tissues.
DR Genevisible; O75881; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0033782; F:24-hydroxycholesterol 7alpha-hydroxylase activity; IEA:UniProtKB-EC.
DR GO; GO:0033783; F:25-hydroxycholesterol 7alpha-hydroxylase activity; IEA:UniProtKB-EC.
DR GO; GO:0047092; F:27-hydroxycholesterol 7-alpha-monooxygenase 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:0008396; F:oxysterol 7-alpha-hydroxylase activity; ISS:UniProtKB.
DR GO; GO:0035754; P:B cell chemotaxis; ISS:UniProtKB.
DR GO; GO:0006699; P:bile acid biosynthetic process; IBA:GO_Central.
DR GO; GO:0042632; P:cholesterol homeostasis; IBA:GO_Central.
DR GO; GO:0008203; P:cholesterol metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0050673; P:epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0030520; P:intracellular estrogen receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0033147; P:negative regulation of intracellular estrogen receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IEA:Ensembl.
DR GO; GO:0060740; P:prostate gland epithelium morphogenesis; IEA:Ensembl.
DR GO; GO:0016125; P:sterol metabolic process; TAS:Reactome.
DR CDD; cd20632; CYP7B1; 1.
DR Gene3D; 1.10.630.10; Cytochrome P450; 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 PANTHER; PTHR24304:SF0; CYTOCHROME P450 7B1; 1.
DR PANTHER; PTHR24304; CYTOCHROME P450 FAMILY 7; 1.
DR Pfam; PF00067; p450; 1.
DR PIRSF; PIRSF000047; Cytochrome_CYPVIIA1; 1.
DR PRINTS; PR00465; EP450IV.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; Cytochrome P450; 1.
PE 1: Evidence at protein level;
KW Cholesterol metabolism; Disease variant; Endoplasmic reticulum; Heme;
KW Hereditary spastic paraplegia; Intrahepatic cholestasis; Iron;
KW Lipid biosynthesis; Lipid metabolism; Membrane; Metal-binding; Microsome;
KW Monooxygenase; Neurodegeneration; Oxidoreductase; Reference proteome;
KW Steroid biosynthesis; Steroid metabolism; Sterol metabolism; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..506
FT /note="Cytochrome P450 7B1"
FT /id="PRO_0000051906"
FT TRANSMEM 17..37
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 289..309
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 449
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:P22680"
FT VARIANT 19
FT /note="L -> P (in dbSNP:rs72554624)"
FT /evidence="ECO:0000269|PubMed:19439420"
FT /id="VAR_075505"
FT VARIANT 57
FT /note="G -> R (in SPG5A; dbSNP:rs121908614)"
FT /evidence="ECO:0000269|PubMed:18252231"
FT /id="VAR_044382"
FT VARIANT 87
FT /note="G -> V (in SPG5A; dbSNP:rs587777221)"
FT /evidence="ECO:0000269|PubMed:21214876"
FT /id="VAR_075506"
FT VARIANT 106
FT /note="H -> Y"
FT /evidence="ECO:0000269|PubMed:19439420"
FT /id="VAR_075507"
FT VARIANT 147
FT /note="G -> D (in SPG5A; uncertain significance;
FT dbSNP:rs754730601)"
FT /evidence="ECO:0000269|PubMed:24117163"
FT /id="VAR_075508"
FT VARIANT 198
FT /note="G -> R (in SPG5A; uncertain significance;
FT dbSNP:rs1805436635)"
FT /evidence="ECO:0000269|PubMed:26714052"
FT /id="VAR_075509"
FT VARIANT 216
FT /note="F -> S (in SPG5A; dbSNP:rs121908612)"
FT /evidence="ECO:0000269|PubMed:18252231"
FT /id="VAR_044383"
FT VARIANT 285
FT /note="H -> L (in SPG5A; dbSNP:rs750781606)"
FT /evidence="ECO:0000269|PubMed:21214876"
FT /id="VAR_075510"
FT VARIANT 287
FT /note="L -> S"
FT /evidence="ECO:0000269|PubMed:19439420"
FT /id="VAR_075511"
FT VARIANT 297
FT /note="T -> A (in SPG5A; dbSNP:rs587777222)"
FT /evidence="ECO:0000269|PubMed:19439420,
FT ECO:0000269|PubMed:21214876"
FT /id="VAR_075512"
FT VARIANT 316
FT /note="A -> AA (in SPG5A; uncertain significance)"
FT /evidence="ECO:0000269|PubMed:24117163"
FT /id="VAR_075513"
FT VARIANT 324
FT /note="R -> H (in dbSNP:rs59035258)"
FT /evidence="ECO:0000269|PubMed:19439420,
FT ECO:0000269|PubMed:26714052"
FT /id="VAR_075514"
FT VARIANT 363
FT /note="S -> F (in SPG5A; dbSNP:rs121908610)"
FT /evidence="ECO:0000269|PubMed:18252231"
FT /id="VAR_044384"
FT VARIANT 417
FT /note="R -> C (in SPG5A; dbSNP:rs367916692)"
FT /evidence="ECO:0000269|PubMed:19439420"
FT /id="VAR_075515"
FT VARIANT 417
FT /note="R -> H (in SPG5A; dbSNP:rs121908611)"
FT /evidence="ECO:0000269|PubMed:18252231,
FT ECO:0000269|PubMed:19439420"
FT /id="VAR_044385"
FT VARIANT 443
FT /note="G -> A (in SPG5A; dbSNP:rs1190562443)"
FT /evidence="ECO:0000269|PubMed:21214876"
FT /id="VAR_075516"
FT VARIANT 470
FT /note="F -> I (in SPG5A; dbSNP:rs267606758)"
FT /evidence="ECO:0000269|PubMed:19439420"
FT /id="VAR_075517"
FT VARIANT 486
FT /note="R -> C (in SPG5A; dbSNP:rs116171274)"
FT /evidence="ECO:0000269|PubMed:19439420,
FT ECO:0000269|PubMed:24117163, ECO:0000269|PubMed:27217339"
FT /id="VAR_075518"
SQ SEQUENCE 506 AA; 58256 MW; 07D3D4B801B6DBD9 CRC64;
MAGEVSAATG RFSLERLGLP GLALAAALLL LALCLLVRRT RRPGEPPLIK GWLPYLGVVL
NLRKDPLRFM KTLQKQHGDT FTVLLGGKYI TFILDPFQYQ LVIKNHKQLS FRVFSNKLLE
KAFSISQLQK NHDMNDELHL CYQFLQGKSL DILLESMMQN LKQVFEPQLL KTTSWDTAEL
YPFCSSIIFE ITFTTIYGKV IVCDNNKFIS ELRDDFLKFD DKFAYLVSNI PIELLGNVKS
IREKIIKCFS SEKLAKMQGW SEVFQSRQDV LEKYYVHEDL EIGAHHLGFL WASVANTIPT
MFWAMYYLLR HPEAMAAVRD EIDRLLQSTG QKKGSGFPIH LTREQLDSLI CLESSIFEAL
RLSSYSTTIR FVEEDLTLSS ETGDYCVRKG DLVAIFPPVL HGDPEIFEAP EEFRYDRFIE
DGKKKTTFFK RGKKLKCYLM PFGTGTSKCP GRFFALMEIK QLLVILLTYF DLEIIDDKPI
GLNYSRLLFG IQYPDSDVLF RYKVKS
//
