CP26B_MOUSE
ID CP26B_MOUSE Reviewed; 512 AA.
AC Q811W2; Q3TM12;
DT 18-APR-2012, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Cytochrome P450 26B1;
DE EC=1.14.13.- {ECO:0000250|UniProtKB:Q9NR63};
DE AltName: Full=Cytochrome P450 retinoic acid-inactivating 2;
DE Short=Cytochrome P450RAI-2;
GN Name=Cyp26b1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Testis;
RX PubMed=12617826; DOI=10.1016/s1567-133x(02)00022-4;
RA Menke D.B., Page D.C.;
RT "Sexually dimorphic gene expression in the developing mouse gonad.";
RL Gene Expr. Patterns 2:359-367(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo, and Mammary gland;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Brain;
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 [6]
RP FUNCTION, DISRUPTION PHENOTYPE, AND DEVELOPMENTAL STAGE.
RX PubMed=16574820; DOI=10.1126/science.1125691;
RA Bowles J., Knight D., Smith C., Wilhelm D., Richman J., Mamiya S.,
RA Yashiro K., Chawengsaksophak K., Wilson M.J., Rossant J., Hamada H.,
RA Koopman P.;
RT "Retinoid signaling determines germ cell fate in mice.";
RL Science 312:596-600(2006).
RN [7]
RP FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=16461896; DOI=10.1073/pnas.0510813103;
RA Koubova J., Menke D.B., Zhou Q., Capel B., Griswold M.D., Page D.C.;
RT "Retinoic acid regulates sex-specific timing of meiotic initiation in
RT mice.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:2474-2479(2006).
RN [8]
RP FUNCTION.
RX PubMed=19838304; DOI=10.1371/journal.pone.0007501;
RA Li H., MacLean G., Cameron D., Clagett-Dame M., Petkovich M.;
RT "Cyp26b1 expression in murine Sertoli cells is required to maintain male
RT germ cells in an undifferentiated state during embryogenesis.";
RL PLoS ONE 4:E7501-E7501(2009).
RN [9]
RP FUNCTION IN SKELETAL DEVELOPMENT.
RX PubMed=22019272; DOI=10.1016/j.ajhg.2011.09.015;
RA Laue K., Pogoda H.M., Daniel P.B., van Haeringen A., Alanay Y.,
RA von Ameln S., Rachwalski M., Morgan T., Gray M.J., Breuning M.H.,
RA Sawyer G.M., Sutherland-Smith A.J., Nikkels P.G., Kubisch C., Bloch W.,
RA Wollnik B., Hammerschmidt M., Robertson S.P.;
RT "Craniosynostosis and multiple skeletal anomalies in humans and zebrafish
RT result from a defect in the localized degradation of retinoic acid.";
RL Am. J. Hum. Genet. 89:595-606(2011).
CC -!- FUNCTION: Involved in the metabolism of retinoic acid (RA), rendering
CC this classical morphogen inactive through oxidation (By similarity).
CC Involved in the specific inactivation of all-trans-retinoic acid (all-
CC trans-RA), with a preference for the following substrates: all-trans-RA
CC > 9-cis-RA > 13-cis-RA (By similarity). Generates several hydroxylated
CC forms of RA, including 4-OH-RA, 4-oxo-RA, and 18-OH-RA (By similarity).
CC Essential for postnatal survival (PubMed:16461896, PubMed:16574820,
CC PubMed:19838304). Plays a central role in germ cell development: acts
CC by degrading RA in the developing testis, preventing STRA8 expression,
CC thereby leading to delay of meiosis (PubMed:16461896, PubMed:16574820,
CC PubMed:19838304). Required for the maintenance of the undifferentiated
CC state of male germ cells during embryonic development in Sertoli cells,
CC inducing arrest in G0 phase of the cell cycle and preventing meiotic
CC entry (PubMed:16461896, PubMed:16574820, PubMed:19838304). Plays a role
CC in skeletal development, both at the level of patterning and in the
CC ossification of bone and the establishment of some synovial joints
CC (PubMed:22019272). {ECO:0000250|UniProtKB:Q9NR63,
CC ECO:0000269|PubMed:16461896, ECO:0000269|PubMed:16574820,
CC ECO:0000269|PubMed:19838304, ECO:0000269|PubMed:22019272}.
CC -!- FUNCTION: Has also a significant activity in oxidation of tazarotenic
CC acid and may therefore metabolize that xenobiotic in vivo.
CC {ECO:0000250|UniProtKB:Q9NR63}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=all-trans-retinoate + O2 + reduced [NADPH--hemoprotein
CC reductase] = all-trans-4-hydroxyretinoate + H(+) + H2O + oxidized
CC [NADPH--hemoprotein reductase]; Xref=Rhea:RHEA:51984, Rhea:RHEA-
CC COMP:11964, Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:15379, ChEBI:CHEBI:35291,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:134178;
CC Evidence={ECO:0000250|UniProtKB:Q9NR63};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:51985;
CC Evidence={ECO:0000250|UniProtKB:Q9NR63};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:Q9Y6A2};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:O43174}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:O43174}. Microsome membrane
CC {ECO:0000250|UniProtKB:O43174}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:O43174}.
CC -!- DEVELOPMENTAL STAGE: In the embryonic male gonad, expressed in somatic
CC cells as early as 11.5 dpc and persist throughout development.
CC Expression is detected in peritubular myoepithelial cells in the
CC postnatal testis, while expression is absent in developing and adult
CC ovaries. {ECO:0000269|PubMed:16461896, ECO:0000269|PubMed:16574820}.
CC -!- DISRUPTION PHENOTYPE: Germ cells enter meiosis precociously in
CC embryonic testes, due to strong-up-regulation of Stra8.
CC {ECO:0000269|PubMed:16574820}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AY134662; AAN08613.1; -; mRNA.
DR EMBL; AK137124; BAE23242.1; -; mRNA.
DR EMBL; AK166211; BAE38630.1; -; mRNA.
DR EMBL; AC153606; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466523; EDK99117.1; -; Genomic_DNA.
DR EMBL; BC059246; AAH59246.1; -; mRNA.
DR CCDS; CCDS20289.1; -.
DR RefSeq; NP_001171184.1; NM_001177713.1.
DR RefSeq; NP_780684.1; NM_175475.3.
DR AlphaFoldDB; Q811W2; -.
DR SMR; Q811W2; -.
DR STRING; 10090.ENSMUSP00000076886; -.
DR iPTMnet; Q811W2; -.
DR PhosphoSitePlus; Q811W2; -.
DR MaxQB; Q811W2; -.
DR PaxDb; Q811W2; -.
DR PRIDE; Q811W2; -.
DR ProteomicsDB; 278003; -.
DR Antibodypedia; 2113; 283 antibodies from 34 providers.
DR Ensembl; ENSMUST00000077705; ENSMUSP00000076886; ENSMUSG00000063415.
DR Ensembl; ENSMUST00000168003; ENSMUSP00000128391; ENSMUSG00000063415.
DR Ensembl; ENSMUST00000204146; ENSMUSP00000145092; ENSMUSG00000063415.
DR GeneID; 232174; -.
DR KEGG; mmu:232174; -.
DR UCSC; uc009coy.2; mouse.
DR CTD; 56603; -.
DR MGI; MGI:2176159; Cyp26b1.
DR VEuPathDB; HostDB:ENSMUSG00000063415; -.
DR eggNOG; KOG0157; Eukaryota.
DR GeneTree; ENSGT00800000124060; -.
DR HOGENOM; CLU_001570_15_6_1; -.
DR InParanoid; Q811W2; -.
DR OMA; WTATRDR; -.
DR OrthoDB; 871849at2759; -.
DR PhylomeDB; Q811W2; -.
DR TreeFam; TF105093; -.
DR Reactome; R-MMU-211916; Vitamins.
DR Reactome; R-MMU-5365859; RA biosynthesis pathway.
DR BioGRID-ORCS; 232174; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Cyp26b1; mouse.
DR PRO; PR:Q811W2; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q811W2; protein.
DR Bgee; ENSMUSG00000063415; Expressed in manus and 220 other tissues.
DR ExpressionAtlas; Q811W2; baseline and differential.
DR Genevisible; Q811W2; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
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; IBA:GO_Central.
DR GO; GO:0016491; F:oxidoreductase activity; IBA:GO_Central.
DR GO; GO:0016709; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, NAD(P)H as one donor, and incorporation of one atom of oxygen; ISS:UniProtKB.
DR GO; GO:0008401; F:retinoic acid 4-hydroxylase activity; ISO:MGI.
DR GO; GO:0001972; F:retinoic acid binding; ISO:MGI.
DR GO; GO:0060349; P:bone morphogenesis; ISO:MGI.
DR GO; GO:0001709; P:cell fate determination; IMP:MGI.
DR GO; GO:0071300; P:cellular response to retinoic acid; IEP:UniProtKB.
DR GO; GO:0070268; P:cornification; IMP:MGI.
DR GO; GO:0030326; P:embryonic limb morphogenesis; IMP:MGI.
DR GO; GO:0061436; P:establishment of skin barrier; IMP:MGI.
DR GO; GO:0001768; P:establishment of T cell polarity; IMP:MGI.
DR GO; GO:0006954; P:inflammatory response; IMP:MGI.
DR GO; GO:0001822; P:kidney development; IEA:Ensembl.
DR GO; GO:0007140; P:male meiotic nuclear division; IMP:MGI.
DR GO; GO:0048387; P:negative regulation of retinoic acid receptor signaling pathway; IMP:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:2001037; P:positive regulation of tongue muscle cell differentiation; IMP:UniProtKB.
DR GO; GO:0009954; P:proximal/distal pattern formation; IMP:MGI.
DR GO; GO:0048385; P:regulation of retinoic acid receptor signaling pathway; IMP:MGI.
DR GO; GO:0045580; P:regulation of T cell differentiation; IMP:MGI.
DR GO; GO:0033189; P:response to vitamin A; IEA:Ensembl.
DR GO; GO:0034653; P:retinoic acid catabolic process; ISO:MGI.
DR GO; GO:0042573; P:retinoic acid metabolic process; ISS:UniProtKB.
DR GO; GO:0048384; P:retinoic acid receptor signaling pathway; IDA:MGI.
DR GO; GO:0007283; P:spermatogenesis; IMP:MGI.
DR GO; GO:0016125; P:sterol metabolic process; IBA:GO_Central.
DR GO; GO:0043587; P:tongue morphogenesis; IMP:UniProtKB.
DR GO; GO:0006805; P:xenobiotic metabolic process; ISS:UniProtKB.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Endoplasmic reticulum; Heme; Iron; Lipid metabolism; Membrane;
KW Metal-binding; Microsome; Monooxygenase; Oxidoreductase;
KW Reference proteome.
FT CHAIN 1..512
FT /note="Cytochrome P450 26B1"
FT /id="PRO_0000416905"
FT BINDING 441
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:0000255"
FT CONFLICT 67..68
FT /note="LQ -> TR (in Ref. 2; BAE38630)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 512 AA; 57375 MW; AAA063DE5718824E CRC64;
MLFEGLELVS ALATLAACLV SVTLLLAVSQ QLWQLRWAAT RDKSCKLPIP KGSMGFPLIG
ETGHWLLQGS GFQSSRREKY GNVFKTHLLG RPLIRVTGAE NVRKILLGEH QLVSTEWPRS
ARVLLGPNTV ANSIGDIHRN KRKVFSKIFS HEALESYLPK IQLVIQDTLR AWSSQPEAIN
VYQEAQRLTF RMAVRVLLGF SIPEEDLGHL FEVYQQFVEN VFSLPVDLPF SGYRRGIQAR
QILQKGLEKA IREKLQCTQG KDYSDALDIL IESSKEHGKE MTMQELKDGT LELIFAAYAT
TASASTSLIM QLLKHPAVLE KLREELRAQG LLHGGGCPCE GTLRLDTLSS LRYLDCVIKE
VMRLFTPVSG GYRTVLQTFE LDGFQIPKGW SVMYSIRDTH DTAPVFKDVN VFDPDRFSQA
RSEDKDGRFH YLPFGGGVRT CLGKHLAKLF LKVLAVELAS TSRFELATRT FPRITLVPVL
HPVDGLSVKF FGLDSNQNEI LPETEAMLSA TV
