Cytochrome P450 26A1

Details

Name
Cytochrome P450 26A1
Kind
protein
Synonyms
  • 1.14.13.-
  • CYP26
  • CYP26A1
  • Cytochrome P450 retinoic acid-inactivating 1
  • Cytochrome P450RAI
  • hP450RAI
  • P450RAI1
  • Retinoic acid 4-hydroxylase
  • Retinoic acid-metabolizing cytochrome
Gene Name
CYP26A1
UniProtKB Entry
O43174Swiss-Prot
Organism
Humans
NCBI Taxonomy ID
9606
Amino acid sequence
>lcl|BSEQ0037239|Cytochrome P450 26A1
MGLPALLASALCTFVLPLLLFLAAIKLWDLYCVSGRDRSCALPLPPGTMGFPFFGETLQM
VLQRRKFLQMKRRKYGFIYKTHLFGRPTVRVMGADNVRRILLGEHRLVSVHWPASVRTIL
GSGCLSNLHDSSHKQRKKVIMRAFSREALECYVPVITEEVGSSLEQWLSCGERGLLVYPE
VKRLMFRIAMRILLGCEPQLAGDGDSEQQLVEAFEEMTRNLFSLPIDVPFSGLYRGMKAR
NLIHARIEQNIRAKICGLRASEAGQGCKDALQLLIEHSWERGERLDMQALKQSSTELLFG
GHETTASAATSLITYLGLYPHVLQKVREELKSKGLLCKSNQDNKLDMEILEQLKYIGCVI
KETLRLNPPVPGGFRVALKTFELNGYQIPKGWNVIYSICDTHDVAEIFTNKEEFNPDRFM
LPHPEDASRFSFIPFGGGLRSCVGKEFAKILLKIFTVELARHCDWQLLNGPPTMKTSPTV
YPVDNLPARFTHFHGEI
Number of residues
497
Molecular Weight
56198.11
Theoretical pI
8.73
GO Classification
Functions
all-trans retinoic acid 18-hydroxylase activity / all-trans retinoic acid 4-hydrolase activity / monooxygenase activity / 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
Processes
kidney development / response to retinoic acid / response to vitamin A / retinoic acid metabolic process / sterol metabolic process
General Function
A cytochrome P450 monooxygenase involved in the metabolism of retinoates (RAs), the active metabolites of vitamin A, and critical signaling molecules in animals (PubMed:22020119, PubMed:9228017, PubMed:9716180). RAs exist as at least four different isomers: all-trans-RA (atRA), 9-cis-RA, 13-cis-RA, and 9,13-dicis-RA, where atRA is considered to be the biologically active isomer, although 9-cis-RA and 13-cis-RA also have activity (Probable). Catalyzes the hydroxylation of atRA primarily at C-4 and C-18, thereby contributing to the regulation of atRA homeostasis and signaling (PubMed:22020119, PubMed:9228017, PubMed:9716180). Hydroxylation of atRA limits its biological activity and initiates a degradative process leading to its eventual elimination (Probable). Involved in the convertion of atRA to all-trans-4-oxo-RA. Able to metabolize other RAs such as 9-cis, 13-cis and 9,13-di-cis RA (By similarity) (PubMed:9228017). Can oxidize all-trans-13,14-dihydroretinoate (DRA) to metabolites which could include all-trans-4-oxo-DRA, all-trans-4-hydroxy-DRA, all-trans-5,8-epoxy-DRA, and all-trans-18-hydroxy-DRA (By similarity). May play a role in the oxidative metabolism of xenobiotics such as tazarotenic acid (PubMed:26937021)
Specific Function
All-trans retinoic acid 18-hydroxylase activity
Pfam Domain Function
Signal Regions
Not Available
Transmembrane Regions
Not Available
Cellular Location
Endoplasmic reticulum membrane
Gene sequence
>lcl|BSEQ0017113|Cytochrome P450 26A1 (CYP26A1)
ATGGGGCTCCCGGCGCTGCTGGCCAGTGCGCTCTGCACCTTCGTGCTGCCGCTGCTGCTC
TTCCTGGCTGCGATCAAGCTCTGGGACCTGTACTGCGTGAGCGGCCGCGACCGCAGTTGT
GCCCTCCCATTGCCCCCCGGGACTATGGGCTTCCCCTTCTTTGGGGAAACCTTGCAGATG
GTACTGCAGCGGAGGAAGTTCCTGCAGATGAAGCGCAGGAAATACGGCTTCATCTACAAG
ACGCATCTGTTCGGGCGGCCCACCGTACGGGTGATGGGCGCGGACAATGTGCGGCGCATC
TTGCTCGGAGAGCACCGGCTGGTGTCGGTCCACTGGCCAGCGTCGGTGCGCACCATTCTG
GGATCTGGCTGCCTCTCTAACCTGCACGACTCCTCGCACAAGCAGCGCAAGAAGGTGATT
ATGCGGGCCTTCAGCCGCGAGGCACTCGAATGCTACGTGCCGGTGATCACCGAGGAAGTG
GGCAGCAGCCTGGAGCAGTGGCTGAGCTGCGGCGAGCGCGGCCTCCTGGTCTACCCCGAG
GTGAAGCGCCTCATGTTCCGAATCGCCATGCGCATCCTACTGGGCTGCGAACCCCAACTG
GCGGGCGACGGGGACTCCGAGCAGCAGCTTGTGGAGGCCTTCGAGGAAATGACCCGCAAT
CTCTTCTCGCTGCCCATCGACGTGCCCTTCAGCGGGCTGTACCGGGGCATGAAGGCGCGG
AACCTCATTCACGCGCGCATCGAGCAGAACATTCGCGCCAAGATCTGCGGGCTGCGGGCA
TCCGAGGCGGGCCAGGGCTGCAAAGACGCGCTGCAGCTGTTGATCGAGCACTCGTGGGAG
AGGGGAGAGCGGCTGGACATGCAGGCACTAAAGCAATCTTCAACCGAACTCCTCTTTGGA
GGACACGAAACCACGGCCAGTGCAGCCACATCTCTGATCACTTACCTGGGGCTCTACCCA
CATGTTCTCCAGAAAGTGCGAGAAGAGCTGAAGAGTAAGGGTTTACTTTGCAAGAGCAAT
CAAGACAACAAGTTGGACATGGAAATTTTGGAACAACTTAAATACATCGGGTGTGTTATT
AAGGAGACCCTTCGACTGAATCCCCCAGTTCCAGGAGGGTTTCGGGTTGCTCTGAAGACT
TTTGAATTAAATGGATACCAGATTCCCAAGGGCTGGAATGTTATCTACAGTATCTGTGAT
ACTCATGATGTGGCAGAGATCTTCACCAACAAGGAAGAATTTAATCCTGACCGATTCATG
CTGCCTCACCCAGAGGATGCATCCAGGTTCAGCTTCATTCCATTTGGAGGAGGCCTTAGG
AGCTGTGTAGGCAAAGAATTTGCAAAAATTCTTCTCAAAATATTTACAGTGGAGCTGGCC
AGGCATTGTGACTGGCAGCTTCTAAATGGACCTCCTACAATGAAAACCAGTCCCACCGTG
TATCCTGTGGACAATCTCCCTGCAAGATTCACCCATTTCCATGGGGAAATCTGA
Chromosome Location
10
Locus
10q23.33
External Identifiers
ResourceLink
UniProtKB IDO43174
UniProtKB Entry NameCP26A_HUMAN
GenBank Gene IDAF005418
GeneCard IDCYP26A1
GenAtlas IDCYP26A1
HGNC IDHGNC:2603
KEGG IDhsa:1592
IUPHAR/Guide To Pharmacology ID1366
NCBI Gene ID1592
General References
  1. White JA, Beckett-Jones B, Guo YD, Dilworth FJ, Bonasoro J, Jones G, Petkovich M: cDNA cloning of human retinoic acid-metabolizing enzyme (hP450RAI) identifies a novel family of cytochromes P450. J Biol Chem. 1997 Jul 25;272(30):18538-41. [Article]
  2. Sonneveld E, van den Brink CE, van der Leede BM, Schulkes RK, Petkovich M, van der Burg B, van der Saag PT: Human retinoic acid (RA) 4-hydroxylase (CYP26) is highly specific for all-trans-RA and can be induced through RA receptors in human breast and colon carcinoma cells. Cell Growth Differ. 1998 Aug;9(8):629-37. [Article]
  3. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  4. Deloukas P, Earthrowl ME, Grafham DV, Rubenfield M, French L, Steward CA, Sims SK, Jones MC, Searle S, Scott C, Howe K, Hunt SE, Andrews TD, Gilbert JG, Swarbreck D, Ashurst JL, Taylor A, Battles J, Bird CP, Ainscough R, Almeida JP, Ashwell RI, Ambrose KD, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Bates K, Beasley H, Bray-Allen S, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Cahill P, Camire D, Carter NP, Chapman JC, Clark SY, Clarke G, Clee CM, Clegg S, Corby N, Coulson A, Dhami P, Dutta I, Dunn M, Faulkner L, Frankish A, Frankland JA, Garner P, Garnett J, Gribble S, Griffiths C, Grocock R, Gustafson E, Hammond S, Harley JL, Hart E, Heath PD, Ho TP, Hopkins B, Horne J, Howden PJ, Huckle E, Hynds C, Johnson C, Johnson D, Kana A, Kay M, Kimberley AM, Kershaw JK, Kokkinaki M, Laird GK, Lawlor S, Lee HM, Leongamornlert DA, Laird G, Lloyd C, Lloyd DM, Loveland J, Lovell J, McLaren S, McLay KE, McMurray A, Mashreghi-Mohammadi M, Matthews L, Milne S, Nickerson T, Nguyen M, Overton-Larty E, Palmer SA, Pearce AV, Peck AI, Pelan S, Phillimore B, Porter K, Rice CM, Rogosin A, Ross MT, Sarafidou T, Sehra HK, Shownkeen R, Skuce CD, Smith M, Standring L, Sycamore N, Tester J, Thorpe A, Torcasso W, Tracey A, Tromans A, Tsolas J, Wall M, Walsh J, Wang H, Weinstock K, West AP, Willey DL, Whitehead SL, Wilming L, Wray PW, Young L, Chen Y, Lovering RC, Moschonas NK, Siebert R, Fechtel K, Bentley D, Durbin R, Hubbard T, Doucette-Stamm L, Beck S, Smith DR, Rogers J: The DNA sequence and comparative analysis of human chromosome 10. Nature. 2004 May 27;429(6990):375-81. [Article]
  5. Trofimova-Griffin ME, Juchau MR: Expression of cytochrome P450RAI (CYP26) in human fetal hepatic and cephalic tissues. Biochem Biophys Res Commun. 1998 Nov 18;252(2):487-91. [Article]

Associated Data

Drug Relations
DrugDrug groupPharmacological action?TypeActionsDetails
TalarozoleinvestigationalyestargetinhibitorDetails
Vitamin Aapproved, nutraceutical, vet_approvedunknownenzymesubstrateinducerDetails
Tretinoinapproved, investigational, nutraceuticalunknownenzymesubstrateDetails
LiarozoleinvestigationalyestargetinhibitorDetails