CP26C_HUMAN
ID CP26C_HUMAN Reviewed; 522 AA.
AC Q6V0L0; Q5VXH6;
DT 19-JUL-2005, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 2.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Cytochrome P450 26C1;
DE EC=1.14.-.-;
GN Name=CYP26C1;
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], TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=14532297; DOI=10.1074/jbc.m308337200;
RA Taimi M., Helvig C., Wisniewski J., Ramshaw H., White J., Amad M.,
RA Korczak B., Petkovich M.;
RT "A novel human cytochrome P450, CYP26C1, involved in metabolism of 9-cis
RT and all-trans isomers of retinoic acid.";
RL J. Biol. Chem. 279:77-85(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [3]
RP INVOLVEMENT IN FFDD4.
RX PubMed=23161670; DOI=10.1093/hmg/dds477;
RA Slavotinek A.M., Mehrotra P., Nazarenko I., Tang P.L., Lao R., Cameron D.,
RA Li B., Chu C., Chou C., Marqueling A.L., Yahyavi M., Cordoro K.,
RA Frieden I., Glaser T., Prescott T., Morren M.A., Devriendt K., Kwok P.Y.,
RA Petkovich M., Desnick R.J.;
RT "Focal facial dermal dysplasia, type IV, is caused by mutations in
RT CYP26C1.";
RL Hum. Mol. Genet. 22:696-703(2013).
CC -!- FUNCTION: Plays a role in retinoic acid metabolism. Acts on retinoids,
CC including all-trans-retinoic acid (RA) and its stereoisomer 9-cis-RA
CC (preferred substrate).
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413; Evidence={ECO:0000250};
CC -!- INTERACTION:
CC Q6V0L0; Q96BD6: SPSB1; NbExp=2; IntAct=EBI-25602589, EBI-2659201;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass membrane
CC protein {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Detected in most tissues at very low level.
CC {ECO:0000269|PubMed:14532297}.
CC -!- INDUCTION: By retinoic acid. {ECO:0000269|PubMed:14532297}.
CC -!- DISEASE: Focal facial dermal dysplasia 4 (FFDD4) [MIM:614974]: A form
CC of focal facial dermal dysplasia, a group of developmental defects
CC characterized by bitemporal or preauricular skin lesions resembling
CC aplasia cutis congenita. Skin defects occur at the sites of facial
CC fusion during embryogenesis, with temporal lesions situated at the
CC junction between the frontonasal and maxillary facial prominences, and
CC preauricular lesions at the meeting point of the maxillary and
CC mandibular prominences. The ectodermal lesions show consistent
CC histologic abnormalities: atrophy and flattening of the epidermis,
CC replacement of the dermis by loose connective tissue, reduced levels of
CC fragmented elastic tissue and absence of the subcutaneous tissues and
CC adnexal structures. FFDD4 is characterized by isolated, preauricular
CC skin lesions. {ECO:0000269|PubMed:23161670}. Note=The disease is caused
CC by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; AY356349; AAQ55485.1; -; mRNA.
DR EMBL; AL358613; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS7425.1; -.
DR RefSeq; NP_899230.2; NM_183374.2.
DR AlphaFoldDB; Q6V0L0; -.
DR SMR; Q6V0L0; -.
DR IntAct; Q6V0L0; 3.
DR STRING; 9606.ENSP00000285949; -.
DR DrugBank; DB00523; Alitretinoin.
DR DrugBank; DB00755; Tretinoin.
DR iPTMnet; Q6V0L0; -.
DR PhosphoSitePlus; Q6V0L0; -.
DR BioMuta; CYP26C1; -.
DR DMDM; 71153209; -.
DR MassIVE; Q6V0L0; -.
DR PaxDb; Q6V0L0; -.
DR PeptideAtlas; Q6V0L0; -.
DR PRIDE; Q6V0L0; -.
DR ProteomicsDB; 67704; -.
DR Antibodypedia; 45703; 158 antibodies from 25 providers.
DR DNASU; 340665; -.
DR Ensembl; ENST00000651965.1; ENSP00000498424.1; ENSG00000187553.10.
DR GeneID; 340665; -.
DR KEGG; hsa:340665; -.
DR MANE-Select; ENST00000651965.1; ENSP00000498424.1; NM_183374.3; NP_899230.2.
DR UCSC; uc010qns.2; human.
DR CTD; 340665; -.
DR DisGeNET; 340665; -.
DR GeneCards; CYP26C1; -.
DR HGNC; HGNC:20577; CYP26C1.
DR HPA; ENSG00000187553; Not detected.
DR MalaCards; CYP26C1; -.
DR MIM; 608428; gene.
DR MIM; 614974; phenotype.
DR neXtProt; NX_Q6V0L0; -.
DR OpenTargets; ENSG00000187553; -.
DR Orphanet; 398189; Focal facial dermal dysplasia type IV.
DR PharmGKB; PA134913464; -.
DR VEuPathDB; HostDB:ENSG00000187553; -.
DR eggNOG; KOG0157; Eukaryota.
DR GeneTree; ENSGT00800000124060; -.
DR HOGENOM; CLU_001570_15_6_1; -.
DR InParanoid; Q6V0L0; -.
DR OMA; AHMCLGL; -.
DR OrthoDB; 574756at2759; -.
DR PhylomeDB; Q6V0L0; -.
DR TreeFam; TF105093; -.
DR PathwayCommons; Q6V0L0; -.
DR Reactome; R-HSA-211916; Vitamins.
DR Reactome; R-HSA-5365859; RA biosynthesis pathway.
DR Reactome; R-HSA-5579004; Defective CYP26C1 causes FFDD4.
DR SignaLink; Q6V0L0; -.
DR BioGRID-ORCS; 340665; 9 hits in 1065 CRISPR screens.
DR GeneWiki; CYP26C1; -.
DR GenomeRNAi; 340665; -.
DR Pharos; Q6V0L0; Tbio.
DR PRO; PR:Q6V0L0; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q6V0L0; protein.
DR Bgee; ENSG00000187553; Expressed in prefrontal cortex and 10 other tissues.
DR ExpressionAtlas; Q6V0L0; baseline and differential.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; IDA:BHF-UCL.
DR GO; GO:0001972; F:retinoic acid binding; IDA:BHF-UCL.
DR GO; GO:0009952; P:anterior/posterior pattern specification; ISS:BHF-UCL.
DR GO; GO:0007417; P:central nervous system development; ISS:BHF-UCL.
DR GO; GO:0048387; P:negative regulation of retinoic acid receptor signaling pathway; NAS:BHF-UCL.
DR GO; GO:0014032; P:neural crest cell development; ISS:BHF-UCL.
DR GO; GO:0048284; P:organelle fusion; ISS:BHF-UCL.
DR GO; GO:0034653; P:retinoic acid catabolic process; IDA:BHF-UCL.
DR GO; GO:0016125; P:sterol metabolic process; IBA:GO_Central.
DR GO; GO:0006766; P:vitamin metabolic process; TAS:Reactome.
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 Ectodermal dysplasia; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..522
FT /note="Cytochrome P450 26C1"
FT /id="PRO_0000051987"
FT TRANSMEM 9..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 459
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 VARIANT 245
FT /note="R -> Q (in dbSNP:rs11187265)"
FT /id="VAR_022886"
FT CONFLICT 447
FT /note="F -> L (in Ref. 1; AAQ55485)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 522 AA; 57111 MW; 5401DF5646E51060 CRC64;
MFPWGLSCLS VLGAAGTALL CAGLLLSLAQ HLWTLRWMLS RDRASTLPLP KGSMGWPFFG
ETLHWLVQGS RFHSSRRERY GTVFKTHLLG RPVIRVSGAE NVRTILLGEH RLVRSQWPQS
AHILLGSHTL LGAVGEPHRR RRKVLARVFS RAALERYVPR LQGALRHEVR SWCAAGGPVS
VYDASKALTF RMAARILLGL RLDEAQCATL ARTFEQLVEN LFSLPLDVPF SGLRKGIRAR
DQLHRHLEGA ISEKLHEDKA AEPGDALDLI IHSARELGHE PSMQELKESA VELLFAAFFT
TASASTSLVL LLLQHPAAIA KIREELVAQG LGRACGCAPG AAGGSEGPPP DCGCEPDLSL
AALGRLRYVD CVVKEVLRLL PPVSGGYRTA LRTFELDGYQ IPKGWSVMYS IRDTHETAAV
YRSPPEGFDP ERFGAAREDS RGASSRFHYI PFGGGARSCL GQELAQAVLQ LLAVELVRTA
RWELATPAFP AMQTVPIVHP VDGLRLFFHP LTPSVAGNGL CL