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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 transcript 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.

Cofactori

hemeBy similarity

Sites

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

GO - Molecular functioni

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

GO - Biological processi

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

Keywords - Molecular functioni

Monooxygenase, Oxidoreductase

Keywords - Ligandi

Heme, Iron, Metal-binding

Enzyme and pathway databases

ReactomeiREACT_13450. Vitamins.
REACT_268561. RA biosynthesis pathway.

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 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

PharmGKBiPA27098.

Chemistry

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

Polymorphism and mutation databases

BioMutaiCYP26A1.

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.
ExpressionAtlasiO43174. baseline and differential.
GenevisibleiO43174. HS.

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.
GeneTreeiENSGT00800000124060.
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. 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)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:
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.
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. Positions 41-490.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9606.ENSP00000224356.

Chemistry

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

Polymorphism and mutation databases

BioMutaiCYP26A1.

Proteomic databases

PaxDbiO43174.
PRIDEiO43174.

Protocols and materials databases

DNASUi1592.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi1592.
GeneCardsiGC10P094823.
HGNCiHGNC:2603. CYP26A1.
MIMi602239. gene.
neXtProtiNX_O43174.
PharmGKBiPA27098.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG2124.
GeneTreeiENSGT00800000124060.
HOGENOMiHOG000220829.
HOVERGENiHBG051099.
InParanoidiO43174.
KOiK07437.
OMAiIRAKICR.
OrthoDBiEOG7F24SP.
PhylomeDBiO43174.
TreeFamiTF105093.

Enzyme and pathway databases

ReactomeiREACT_13450. Vitamins.
REACT_268561. RA biosynthesis pathway.

Miscellaneous databases

ChiTaRSiCYP26A1. human.
GeneWikiiCYP26A1.
GenomeRNAii1592.
NextBioi35469055.
PROiO43174.
SOURCEiSearch...

Gene expression databases

BgeeiO43174.
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...

Publicationsi

« Hide 'large scale' publications
  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: July 22, 2015
This is version 131 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

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 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.