ID   CP26B_DANRE             Reviewed;         511 AA.
AC   Q6EIG3; Q6NY30;
DT   29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT   16-AUG-2004, sequence version 1.
DT   03-AUG-2022, entry version 112.
DE   RecName: Full=Cytochrome P450 26B1;
DE            Short=Cyp26B1;
DE            EC=1.14.13.- {ECO:0000250|UniProtKB:Q9NR63};
DE   AltName: Full=Retinoic acid-metabolizing cytochrome;
GN   Name=cyp26b1 {ECO:0000312|EMBL:AAQ82596.1};
OS   Danio rerio (Zebrafish) (Brachydanio rerio).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC   Danionidae; Danioninae; Danio.
OX   NCBI_TaxID=7955;
RN   [1] {ECO:0000305, ECO:0000312|EMBL:AAQ82596.1}
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND DEVELOPMENTAL STAGE.
RX   PubMed=15661642; DOI=10.1016/j.modgep.2004.09.011;
RA   Zhao Q., Dobbs-McAuliffe B., Linney E.;
RT   "Expression of cyp26b1 during zebrafish early development.";
RL   Gene Expr. Patterns 5:363-369(2005).
RN   [2] {ECO:0000305, ECO:0000312|EMBL:AAH66759.1}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Embryo {ECO:0000312|EMBL:AAH66759.1};
RG   NIH - Zebrafish Gene Collection (ZGC) project;
RL   Submitted (MAR-2004) to the EMBL/GenBank/DDBJ databases.
RN   [3]
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 (PubMed:15661642).
CC       Appears to be involved in the inactivation of all-trans-retinoic acid
CC       (RA) (PubMed:15661642). Plays a role in skeletal development
CC       (PubMed:22019272). {ECO:0000269|PubMed:15661642,
CC       ECO:0000269|PubMed:22019272}.
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: Expressed zygotically. Weak expression at 75%
CC       epiboly. At the 2-somite stage, expressed in the presumptive rhombomere
CC       4 (r4) region partially overlapping with the r3 region. At the 10-
CC       somite stage, expressed in the r4, r3 and r2 regions. At the 14-somite
CC       stage, expression extends to the r5 and r6 regions and is observed in
CC       the diencephalon. At 24-48 hours post-fertilization (hpf), additionally
CC       expressed in the eye, midbrain-hindbrain boundary, cerebellum, pectoral
CC       fin and the pharyngeal arch primordia. {ECO:0000269|PubMed:15661642}.
CC   -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000255}.
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DR   EMBL; AY321366; AAQ82596.1; -; mRNA.
DR   EMBL; BC066759; AAH66759.1; -; mRNA.
DR   RefSeq; NP_997831.1; NM_212666.1.
DR   AlphaFoldDB; Q6EIG3; -.
DR   SMR; Q6EIG3; -.
DR   STRING; 7955.ENSDARP00000101543; -.
DR   PaxDb; Q6EIG3; -.
DR   GeneID; 324188; -.
DR   KEGG; dre:324188; -.
DR   CTD; 56603; -.
DR   ZFIN; ZDB-GENE-030131-2908; cyp26b1.
DR   eggNOG; KOG0157; Eukaryota.
DR   InParanoid; Q6EIG3; -.
DR   OrthoDB; 871849at2759; -.
DR   PhylomeDB; Q6EIG3; -.
DR   TreeFam; TF105093; -.
DR   Reactome; R-DRE-211916; Vitamins.
DR   Reactome; R-DRE-5365859; RA biosynthesis pathway.
DR   PRO; PR:Q6EIG3; -.
DR   Proteomes; UP000000437; Genome assembly.
DR   Proteomes; UP000814640; Unplaced.
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:0008401; F:retinoic acid 4-hydroxylase activity; ISS:UniProtKB.
DR   GO; GO:0060349; P:bone morphogenesis; IMP:ZFIN.
DR   GO; GO:0060536; P:cartilage morphogenesis; IMP:ZFIN.
DR   GO; GO:0060365; P:coronal suture morphogenesis; IMP:ZFIN.
DR   GO; GO:0060363; P:cranial suture morphogenesis; IMP:ZFIN.
DR   GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IMP:ZFIN.
DR   GO; GO:0060323; P:head morphogenesis; IMP:ZFIN.
DR   GO; GO:0030902; P:hindbrain development; IGI:ZFIN.
DR   GO; GO:0048387; P:negative regulation of retinoic acid receptor signaling pathway; IDA:UniProtKB.
DR   GO; GO:0042476; P:odontogenesis; IMP:ZFIN.
DR   GO; GO:0030278; P:regulation of ossification; IMP:ZFIN.
DR   GO; GO:0034653; P:retinoic acid catabolic process; IMP:ZFIN.
DR   GO; GO:0042573; P:retinoic acid metabolic process; TAS:UniProtKB.
DR   GO; GO:0021661; P:rhombomere 4 morphogenesis; IGI:ZFIN.
DR   GO; GO:0016125; P:sterol metabolic process; IBA:GO_Central.
DR   GO; GO:0035992; P:tendon formation; IMP:ZFIN.
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..511
FT                   /note="Cytochrome P450 26B1"
FT                   /id="PRO_0000051986"
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|UniProtKB:P00179"
FT   CONFLICT        29
FT                   /note="P -> S (in Ref. 2; AAH66759)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   511 AA;  57598 MW;  CBEF6E42745AB381 CRC64;
     MLFESFDLVS ALATLAACLV SMALLLAVPQ QLWQLRWTAT RDKSCKLPMP KGSMGFPIIG
     ETCHWFFQGA GFHASRRQKY GNVFKTHLLG RPLIRVTGAE NVRKVLMGEH SLVTVDWPQS
     TSTLLGPNSL ANSIGDIHRK RRKIFAKVFS HEALESYLPK IQQVIQETLR VWSSNPDPIN
     VYRESQRLSF NMAVRVLLGF RIPEEEMHCL FSTFQEFVEN VFSLPIDLPF SGYRKGIRAR
     DSLQKSIEKA IREKPLHTQG KDYTDALDVL LESAKENNTE LTMQELKEST IELIFAAFAT
     TASASTSLVM QLLRHPAVLE KLREELRSCG LLHDGCLCQG ELRLDSIISL KYLDCVIKEV
     LRLFAPVSGG YRIATQTFEL DGVQVPKGWS VMYSIRDTHD TSAVFKDVEA FDPDRFSPER
     SEDREGRFHY LPFGGGVRSC LGKQLATLFL KLLAVELAGG SRFELSTRTF PRMISVPVVH
     PTDGLRVKFF GLDSNQNQIM AKSDEMLDAT V