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Protein

Cytochrome P450 26A1

Gene

CYP26A1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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.2 Publications
Has also a significant activity in oxidation of tazarotenic acid and may therefore metabolize that xenobiotic in vivo.1 Publication

Cofactori

hemeBy similarity

Kineticsi

  1. KM=0.24 µM for tazarotenic acid (measured in vitro by the production of tazarotenic acid-sulfoxide)1 Publication
  2. KM=0.39 µM for tazarotenic acid (measured in vitro by the production of hydroxytazarotenic acid)1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Metal bindingi442Iron (heme axial ligand)Sequence analysis1

    GO - Molecular functioni

    • heme binding Source: BHF-UCL
    • iron ion binding Source: InterPro
    • 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 Source: UniProtKB
    • oxygen binding Source: ProtInc
    • retinoic acid 4-hydroxylase activity Source: UniProtKB
    • retinoic acid binding Source: BHF-UCL

    GO - Biological processi

    • negative regulation of retinoic acid receptor signaling pathway Source: BHF-UCL
    • retinoic acid catabolic process Source: BHF-UCL
    • retinoic acid metabolic process Source: UniProtKB
    • vitamin metabolic process Source: Reactome
    • xenobiotic metabolic process Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Monooxygenase, Oxidoreductase

    Keywords - Ligandi

    Heme, Iron, Metal-binding

    Enzyme and pathway databases

    BioCyciZFISH:ENSG00000095596-MONOMER.
    ReactomeiR-HSA-211916. Vitamins.
    R-HSA-5365859. RA biosynthesis pathway.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cytochrome P450 26A1 (EC:1.14.13.-3 Publications)
    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
    Proteomesi
    • UP000005640 Componenti: Chromosome 10

    Organism-specific databases

    HGNCiHGNC:2603. CYP26A1.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    Pathology & Biotechi

    Organism-specific databases

    DisGeNETi1592.
    OpenTargetsiENSG00000095596.
    PharmGKBiPA27098.

    Chemistry databases

    ChEMBLiCHEMBL5141.
    DrugBankiDB00459. Acitretin.
    DB01026. Ketoconazole.
    DB00162. Vitamin A.
    GuidetoPHARMACOLOGYi1366.

    Polymorphism and mutation databases

    BioMutaiCYP26A1.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000519801 – 497Cytochrome P450 26A1Add BLAST497

    Proteomic databases

    PaxDbiO43174.
    PeptideAtlasiO43174.
    PRIDEiO43174.

    PTM databases

    iPTMnetiO43174.
    PhosphoSitePlusiO43174.

    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

    BgeeiENSG00000095596.
    CleanExiHS_CYP26A1.
    ExpressionAtlasiO43174. baseline and differential.
    GenevisibleiO43174. HS.

    Interactioni

    Protein-protein interaction databases

    STRINGi9606.ENSP00000224356.

    Chemistry databases

    BindingDBiO43174.

    Structurei

    3D structure databases

    ProteinModelPortaliO43174.
    SMRiO43174.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the cytochrome P450 family.Curated

    Phylogenomic databases

    eggNOGiKOG0157. Eukaryota.
    COG2124. LUCA.
    GeneTreeiENSGT00800000124060.
    HOGENOMiHOG000220829.
    HOVERGENiHBG051099.
    InParanoidiO43174.
    KOiK07437.
    OMAiIRAKICR.
    OrthoDBiEOG091G0K6Z.
    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. AlignAdd to basket

    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

            10         20         30         40         50
    MGLPALLASA LCTFVLPLLL FLAAIKLWDL YCVSGRDRSC ALPLPPGTMG
    60 70 80 90 100
    FPFFGETLQM VLQRRKFLQM KRRKYGFIYK THLFGRPTVR VMGADNVRRI
    110 120 130 140 150
    LLGEHRLVSV HWPASVRTIL GSGCLSNLHD SSHKQRKKVI MRAFSREALE
    160 170 180 190 200
    CYVPVITEEV GSSLEQWLSC GERGLLVYPE VKRLMFRIAM RILLGCEPQL
    210 220 230 240 250
    AGDGDSEQQL VEAFEEMTRN LFSLPIDVPF SGLYRGMKAR NLIHARIEQN
    260 270 280 290 300
    IRAKICGLRA SEAGQGCKDA LQLLIEHSWE RGERLDMQAL KQSSTELLFG
    310 320 330 340 350
    GHETTASAAT SLITYLGLYP HVLQKVREEL KSKGLLCKSN QDNKLDMEIL
    360 370 380 390 400
    EQLKYIGCVI KETLRLNPPV PGGFRVALKT FELNGYQIPK GWNVIYSICD
    410 420 430 440 450
    THDVAEIFTN KEEFNPDRFM LPHPEDASRF SFIPFGGGLR SCVGKEFAKI
    460 470 480 490
    LLKIFTVELA RHCDWQLLNG PPTMKTSPTV YPVDNLPARF THFHGEI
    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)DescriptionActionsGraphical viewLength
    Sequence conflicti104 – 105EH → DD in AAB88881 (PubMed:9228017).Curated2
    Sequence conflicti136R → G in BAG51346 (PubMed:14702039).Curated1

    Alternative sequence

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Alternative sequenceiVSP_0450871 – 69Missing in isoform 2. 1 PublicationAdd BLAST69

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    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:
    EMBLi
    GenBanki
    DDBJi
    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.

    3D structure databases

    ProteinModelPortaliO43174.
    SMRiO43174.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    STRINGi9606.ENSP00000224356.

    Chemistry databases

    BindingDBiO43174.
    ChEMBLiCHEMBL5141.
    DrugBankiDB00459. Acitretin.
    DB01026. Ketoconazole.
    DB00162. Vitamin A.
    GuidetoPHARMACOLOGYi1366.

    PTM databases

    iPTMnetiO43174.
    PhosphoSitePlusiO43174.

    Polymorphism and mutation databases

    BioMutaiCYP26A1.

    Proteomic databases

    PaxDbiO43174.
    PeptideAtlasiO43174.
    PRIDEiO43174.

    Protocols and materials databases

    DNASUi1592.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

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

    Organism-specific databases

    CTDi1592.
    DisGeNETi1592.
    GeneCardsiCYP26A1.
    HGNCiHGNC:2603. CYP26A1.
    MIMi602239. gene.
    neXtProtiNX_O43174.
    OpenTargetsiENSG00000095596.
    PharmGKBiPA27098.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG0157. Eukaryota.
    COG2124. LUCA.
    GeneTreeiENSGT00800000124060.
    HOGENOMiHOG000220829.
    HOVERGENiHBG051099.
    InParanoidiO43174.
    KOiK07437.
    OMAiIRAKICR.
    OrthoDBiEOG091G0K6Z.
    PhylomeDBiO43174.
    TreeFamiTF105093.

    Enzyme and pathway databases

    BioCyciZFISH:ENSG00000095596-MONOMER.
    ReactomeiR-HSA-211916. Vitamins.
    R-HSA-5365859. RA biosynthesis pathway.

    Miscellaneous databases

    ChiTaRSiCYP26A1. human.
    GeneWikiiCYP26A1.
    GenomeRNAii1592.
    PROiO43174.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000095596.
    CleanExiHS_CYP26A1.
    ExpressionAtlasiO43174. baseline and differential.
    GenevisibleiO43174. HS.

    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]
    ProtoNetiSearch...

    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: November 2, 2016
    This is version 140 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

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.