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O43174

- CP26A_HUMAN

UniProt

O43174 - CP26A_HUMAN

Protein

Cytochrome P450 26A1

Gene

CYP26A1

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 122 (01 Oct 2014)
      Sequence version 2 (16 Dec 2008)
      Previous versions | rss
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    Functioni

    Plays a key role in retinoic acid metabolism. Acts on retinoids, including all-trans-retinoic acid (RA) and its stereoisomer 9-cis-RA. Capable of both 4-hydroxylation and 18-hydroxylation. Responsible for generation of several hydroxylated forms of RA, including 4-OH-RA, 4-oxo-RA and 18-OH-RA.

    Cofactori

    Heme group.By similarity

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Metal bindingi442 – 4421Iron (heme axial ligand)Sequence Analysis

    GO - Molecular functioni

    1. heme binding Source: BHF-UCL
    2. iron ion binding Source: InterPro
    3. oxygen binding Source: ProtInc
    4. retinoic acid 4-hydroxylase activity Source: BHF-UCL
    5. retinoic acid binding Source: BHF-UCL

    GO - Biological processi

    1. anterior/posterior pattern specification Source: Ensembl
    2. cellular response to retinoic acid Source: Ensembl
    3. central nervous system development Source: Ensembl
    4. metabolic process Source: ProtInc
    5. negative regulation of retinoic acid receptor signaling pathway Source: BHF-UCL
    6. neural crest cell development Source: Ensembl
    7. retinoic acid catabolic process Source: BHF-UCL
    8. retinoic acid receptor signaling pathway Source: Ensembl
    9. small molecule metabolic process Source: Reactome
    10. vitamin metabolic process Source: Reactome
    11. xenobiotic metabolic process Source: Reactome

    Keywords - Molecular functioni

    Monooxygenase, Oxidoreductase

    Keywords - Ligandi

    Heme, Iron, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_13450. Vitamins.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cytochrome P450 26A1 (EC:1.14.-.-)
    Alternative name(s):
    Cytochrome P450 retinoic acid-inactivating 1
    Short name:
    Cytochrome P450RAI
    Short name:
    hP450RAI
    Retinoic acid 4-hydroxylase
    Retinoic acid-metabolizing cytochrome
    Gene namesi
    Name:CYP26A1
    Synonyms:CYP26, P450RAI1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 10

    Organism-specific databases

    HGNCiHGNC:2603. CYP26A1.

    Subcellular locationi

    GO - Cellular componenti

    1. endoplasmic reticulum membrane Source: Reactome

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA27098.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 497497Cytochrome P450 26A1PRO_0000051980Add
    BLAST

    Proteomic databases

    PaxDbiO43174.
    PRIDEiO43174.

    Expressioni

    Tissue specificityi

    Highest levels in adult liver, heart, pituitary gland, adrenal gland, placenta and regions of the brain.1 Publication

    Inductioni

    By retinoic acid.

    Gene expression databases

    BgeeiO43174.
    CleanExiHS_CYP26A1.
    GenevestigatoriO43174.

    Organism-specific databases

    HPAiCAB015447.

    Interactioni

    Protein-protein interaction databases

    STRINGi9606.ENSP00000224356.

    Structurei

    3D structure databases

    ProteinModelPortaliO43174.
    SMRiO43174. Positions 41-490.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the cytochrome P450 family.Curated

    Phylogenomic databases

    eggNOGiCOG2124.
    HOGENOMiHOG000220829.
    HOVERGENiHBG051099.
    InParanoidiO43174.
    KOiK07437.
    OMAiIRAKICR.
    OrthoDBiEOG7F24SP.
    PhylomeDBiO43174.
    TreeFamiTF105093.

    Family and domain databases

    Gene3Di1.10.630.10. 1 hit.
    InterProiIPR001128. Cyt_P450.
    IPR017972. Cyt_P450_CS.
    IPR002403. Cyt_P450_E_grp-IV.
    [Graphical view]
    PfamiPF00067. p450. 1 hit.
    [Graphical view]
    PRINTSiPR00465. EP450IV.
    PR00385. P450.
    SUPFAMiSSF48264. SSF48264. 1 hit.
    PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: O43174-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MGLPALLASA LCTFVLPLLL FLAAIKLWDL YCVSGRDRSC ALPLPPGTMG    50
    FPFFGETLQM VLQRRKFLQM KRRKYGFIYK THLFGRPTVR VMGADNVRRI 100
    LLGEHRLVSV HWPASVRTIL GSGCLSNLHD SSHKQRKKVI MRAFSREALE 150
    CYVPVITEEV GSSLEQWLSC GERGLLVYPE VKRLMFRIAM RILLGCEPQL 200
    AGDGDSEQQL VEAFEEMTRN LFSLPIDVPF SGLYRGMKAR NLIHARIEQN 250
    IRAKICGLRA SEAGQGCKDA LQLLIEHSWE RGERLDMQAL KQSSTELLFG 300
    GHETTASAAT SLITYLGLYP HVLQKVREEL KSKGLLCKSN QDNKLDMEIL 350
    EQLKYIGCVI KETLRLNPPV PGGFRVALKT FELNGYQIPK GWNVIYSICD 400
    THDVAEIFTN KEEFNPDRFM LPHPEDASRF SFIPFGGGLR SCVGKEFAKI 450
    LLKIFTVELA RHCDWQLLNG PPTMKTSPTV YPVDNLPARF THFHGEI 497
    Length:497
    Mass (Da):56,199
    Last modified:December 16, 2008 - v2
    Checksum:i834318FA493E76D4
    GO
    Isoform 2 (identifier: O43174-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-69: Missing.

    Note: No experimental confirmation available.

    Show »
    Length:428
    Mass (Da):48,558
    Checksum:iE5FA93A5DB86CDCA
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti104 – 1052EH → DD in AAB88881. (PubMed:9228017)Curated
    Sequence conflicti136 – 1361R → G in BAG51346. (PubMed:14702039)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 6969Missing in isoform 2. 1 PublicationVSP_045087Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF005418 mRNA. Translation: AAB88881.1.
    AK027560 mRNA. Translation: BAG51346.1.
    AL358613 Genomic DNA. Translation: CAH72803.1.
    AL358613 Genomic DNA. Translation: CAH72804.1.
    CH471066 Genomic DNA. Translation: EAW50078.1.
    CH471066 Genomic DNA. Translation: EAW50079.1.
    CCDSiCCDS7426.1. [O43174-1]
    CCDS7427.1. [O43174-2]
    RefSeqiNP_000774.2. NM_000783.3. [O43174-1]
    NP_476498.1. NM_057157.2. [O43174-2]
    UniGeneiHs.150595.

    Genome annotation databases

    EnsembliENST00000224356; ENSP00000224356; ENSG00000095596. [O43174-1]
    ENST00000371531; ENSP00000360586; ENSG00000095596. [O43174-2]
    GeneIDi1592.
    KEGGihsa:1592.
    UCSCiuc001kik.1. human. [O43174-1]

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF005418 mRNA. Translation: AAB88881.1 .
    AK027560 mRNA. Translation: BAG51346.1 .
    AL358613 Genomic DNA. Translation: CAH72803.1 .
    AL358613 Genomic DNA. Translation: CAH72804.1 .
    CH471066 Genomic DNA. Translation: EAW50078.1 .
    CH471066 Genomic DNA. Translation: EAW50079.1 .
    CCDSi CCDS7426.1. [O43174-1 ]
    CCDS7427.1. [O43174-2 ]
    RefSeqi NP_000774.2. NM_000783.3. [O43174-1 ]
    NP_476498.1. NM_057157.2. [O43174-2 ]
    UniGenei Hs.150595.

    3D structure databases

    ProteinModelPortali O43174.
    SMRi O43174. Positions 41-490.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    STRINGi 9606.ENSP00000224356.

    Chemistry

    BindingDBi O43174.
    ChEMBLi CHEMBL5141.

    Proteomic databases

    PaxDbi O43174.
    PRIDEi O43174.

    Protocols and materials databases

    DNASUi 1592.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000224356 ; ENSP00000224356 ; ENSG00000095596 . [O43174-1 ]
    ENST00000371531 ; ENSP00000360586 ; ENSG00000095596 . [O43174-2 ]
    GeneIDi 1592.
    KEGGi hsa:1592.
    UCSCi uc001kik.1. human. [O43174-1 ]

    Organism-specific databases

    CTDi 1592.
    GeneCardsi GC10P094823.
    HGNCi HGNC:2603. CYP26A1.
    HPAi CAB015447.
    MIMi 602239. gene.
    neXtProti NX_O43174.
    PharmGKBi PA27098.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi COG2124.
    HOGENOMi HOG000220829.
    HOVERGENi HBG051099.
    InParanoidi O43174.
    KOi K07437.
    OMAi IRAKICR.
    OrthoDBi EOG7F24SP.
    PhylomeDBi O43174.
    TreeFami TF105093.

    Enzyme and pathway databases

    Reactomei REACT_13450. Vitamins.

    Miscellaneous databases

    ChiTaRSi CYP26A1. human.
    GeneWikii CYP26A1.
    GenomeRNAii 1592.
    NextBioi 35469055.
    PROi O43174.
    SOURCEi Search...

    Gene expression databases

    Bgeei O43174.
    CleanExi HS_CYP26A1.
    Genevestigatori O43174.

    Family and domain databases

    Gene3Di 1.10.630.10. 1 hit.
    InterProi IPR001128. Cyt_P450.
    IPR017972. Cyt_P450_CS.
    IPR002403. Cyt_P450_E_grp-IV.
    [Graphical view ]
    Pfami PF00067. p450. 1 hit.
    [Graphical view ]
    PRINTSi PR00465. EP450IV.
    PR00385. P450.
    SUPFAMi SSF48264. SSF48264. 1 hit.
    PROSITEi PS00086. CYTOCHROME_P450. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "cDNA cloning of human retinoic acid-metabolizing enzyme (hP450RAI) identifies a novel family of cytochromes P450."
      White J.A., Beckett-Jones B., Guo Y.-D., Dilworth F.J., Bonasoro J., Jones G., Petkovich M.
      J. Biol. Chem. 272:18538-18541(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    2. "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."
      Sonneveld E., van den Brink C.E., van der Leede B.M., Schulkes R.K., Petkovich M., van der Burg B., van der Saag P.T.
      Cell Growth Differ. 9:629-637(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      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 T.-O., 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.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    4. "The DNA sequence and comparative analysis of human chromosome 10."
      Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J.
      , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., 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 A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.
      Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    6. "Expression of cytochrome P450RAI (CYP26) in human fetal hepatic and cephalic tissues."
      Trofimova-Griffin M.E., Juchau M.R.
      Biochem. Biophys. Res. Commun. 252:487-491(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiCP26A_HUMAN
    AccessioniPrimary (citable) accession number: O43174
    Secondary accession number(s): B3KNI4, Q5VXH9, Q5VXI0
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 15, 1998
    Last sequence update: December 16, 2008
    Last modified: October 1, 2014
    This is version 122 of the entry and version 2 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 10
      Human chromosome 10: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3