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Protein

Cytochrome P450 2A13

Gene

CYP2A13

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

Functioni

Exhibits a coumarin 7-hydroxylase activity. Active in the metabolic activation of hexamethylphosphoramide, N,N-dimethylaniline, 2'-methoxyacetophenone, N-nitrosomethylphenylamine, and the tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. Possesses phenacetin O-deethylation activity.1 Publication

Catalytic activityi

RH + reduced flavoprotein + O2 = ROH + oxidized flavoprotein + H2O.

Cofactori

Kineticsi

  1. KM=10.7 µM for phenacetin1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei297 – 2971Substrate
    Metal bindingi439 – 4391Iron (heme axial ligand)

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Monooxygenase, Oxidoreductase

    Keywords - Ligandi

    Heme, Iron, Metal-binding

    Enzyme and pathway databases

    ReactomeiREACT_13543. Xenobiotics.
    REACT_13797. CYP2E1 reactions.
    REACT_13814. Fatty acids.
    REACT_264461. Aflatoxin activation and detoxification.
    SABIO-RKQ16696.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Cytochrome P450 2A13 (EC:1.14.14.1)
    Alternative name(s):
    CYPIIA13
    Gene namesi
    Name:CYP2A13
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 19

    Organism-specific databases

    HGNCiHGNC:2608. CYP2A13.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Endoplasmic reticulum, Membrane, Microsome

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi110 – 1101L → V: Decreases phenacetin O-deethylation activity 8 fold. 1 Publication
    Mutagenesisi117 – 1171A → V: Increases phenacetin O-deethylation activity 5 fold. 1 Publication
    Mutagenesisi208 – 2081S → I: Decreases phenacetin O-deethylation activity 10 fold. 1 Publication
    Mutagenesisi213 – 2131A → S: Decreases phenacetin O-deethylation activity 2 fold. 1 Publication
    Mutagenesisi300 – 3001F → I: Decreases phenacetin O-deethylation activity 40 fold. 1 Publication
    Mutagenesisi301 – 3011A → G: Decreases phenacetin O-deethylation activity 20 fold. 1 Publication
    Mutagenesisi365 – 3651M → V: Decreases phenacetin O-deethylation activity 7 fold. 1 Publication
    Mutagenesisi366 – 3661L → I: Increases phenacetin O-deethylation activity 3 fold. 1 Publication
    Mutagenesisi369 – 3691G → S: Decreases phenacetin O-deethylation activity 9 fold. 1 Publication
    Mutagenesisi372 – 3721H → R: Decreases phenacetin O-deethylation activity 3 fold. 1 Publication

    Organism-specific databases

    PharmGKBiPA27101.

    Chemistry

    DrugBankiDB00553. Methoxsalen.
    DB00184. Nicotine.
    DB00624. Testosterone.

    Polymorphism and mutation databases

    BioMutaiCYP2A13.
    DMDMi77416854.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 494494Cytochrome P450 2A13PRO_0000051676Add
    BLAST

    Proteomic databases

    PaxDbiQ16696.
    PRIDEiQ16696.

    PTM databases

    PhosphoSiteiQ16696.

    Expressioni

    Tissue specificityi

    Expressed in liver and a number of extrahepatic tissues, including nasal mucosa, lung, trachea, brain, mammary gland, prostate, testis, and uterus, but not in heart, kidney, bone marrow, colon, small intestine, spleen, stomach, thymus, or skeletal muscle.1 Publication

    Gene expression databases

    BgeeiQ16696.
    CleanExiHS_CYP2A13.
    GenevestigatoriQ16696.

    Organism-specific databases

    HPAiHPA046713.
    HPA047262.

    Interactioni

    Protein-protein interaction databases

    BioGridi107931. 1 interaction.
    STRINGi9606.ENSP00000332679.

    Structurei

    Secondary structure

    1
    494
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Turni41 – 433Combined sources
    Helixi46 – 483Combined sources
    Helixi51 – 533Combined sources
    Helixi54 – 6512Combined sources
    Beta strandi67 – 737Combined sources
    Beta strandi76 – 816Combined sources
    Helixi84 – 918Combined sources
    Turni92 – 987Combined sources
    Helixi105 – 1117Combined sources
    Turni116 – 1183Combined sources
    Helixi121 – 13717Combined sources
    Turni138 – 1414Combined sources
    Helixi143 – 16119Combined sources
    Turni162 – 1654Combined sources
    Helixi171 – 18717Combined sources
    Helixi196 – 21217Combined sources
    Helixi215 – 22713Combined sources
    Beta strandi230 – 2323Combined sources
    Helixi233 – 25624Combined sources
    Helixi267 – 27711Combined sources
    Turni278 – 2803Combined sources
    Helixi288 – 31932Combined sources
    Helixi321 – 33414Combined sources
    Beta strandi337 – 3393Combined sources
    Helixi343 – 3486Combined sources
    Helixi350 – 36314Combined sources
    Beta strandi378 – 3803Combined sources
    Beta strandi383 – 3853Combined sources
    Beta strandi390 – 3934Combined sources
    Helixi395 – 3995Combined sources
    Turni402 – 4043Combined sources
    Helixi413 – 4164Combined sources
    Beta strandi419 – 4213Combined sources
    Helixi442 – 45918Combined sources
    Beta strandi460 – 4667Combined sources
    Helixi468 – 4703Combined sources
    Beta strandi476 – 4838Combined sources
    Beta strandi489 – 4935Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2P85X-ray2.35A/B/C/D/E/F26-494[»]
    2PG5X-ray1.95A/B/C/D31-494[»]
    2PG6X-ray2.53A/B/C/D31-494[»]
    2PG7X-ray2.80A/B/C/D31-494[»]
    3T3SX-ray3.00A/B/C/D/E/F/G/H31-494[»]
    4EJGX-ray2.50A/B/C/D/E/F/G/H31-494[»]
    4EJHX-ray2.35A/B/C/D/E/F/G/H31-494[»]
    4EJIX-ray2.10A31-494[»]
    ProteinModelPortaliQ16696.
    SMRiQ16696. Positions 31-494.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ16696.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the cytochrome P450 family.Curated

    Phylogenomic databases

    eggNOGiCOG2124.
    GeneTreeiENSGT00760000118775.
    HOGENOMiHOG000036992.
    HOVERGENiHBG015789.
    InParanoidiQ16696.
    KOiK17685.
    OMAiRGTHGAN.
    OrthoDBiEOG7RBZ85.
    PhylomeDBiQ16696.
    TreeFamiTF352043.

    Family and domain databases

    Gene3Di1.10.630.10. 1 hit.
    InterProiIPR001128. Cyt_P450.
    IPR017972. Cyt_P450_CS.
    IPR002401. Cyt_P450_E_grp-I.
    IPR008067. Cyt_P450_E_grp-I_CYP2A-like.
    [Graphical view]
    PfamiPF00067. p450. 1 hit.
    [Graphical view]
    PRINTSiPR00463. EP450I.
    PR01684. EP450ICYP2A.
    PR00385. P450.
    SUPFAMiSSF48264. SSF48264. 1 hit.
    PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q16696-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MLASGLLLVT LLACLTVMVL MSVWRQRKSR GKLPPGPTPL PFIGNYLQLN
    60 70 80 90 100
    TEQMYNSLMK ISERYGPVFT IHLGPRRVVV LCGHDAVKEA LVDQAEEFSG
    110 120 130 140 150
    RGEQATFDWL FKGYGVAFSN GERAKQLRRF SIATLRGFGV GKRGIEERIQ
    160 170 180 190 200
    EEAGFLIDAL RGTHGANIDP TFFLSRTVSN VISSIVFGDR FDYEDKEFLS
    210 220 230 240 250
    LLRMMLGSFQ FTATSTGQLY EMFSSVMKHL PGPQQQAFKE LQGLEDFIAK
    260 270 280 290 300
    KVEHNQRTLD PNSPRDFIDS FLIRMQEEEK NPNTEFYLKN LVMTTLNLFF
    310 320 330 340 350
    AGTETVSTTL RYGFLLLMKH PEVEAKVHEE IDRVIGKNRQ PKFEDRAKMP
    360 370 380 390 400
    YTEAVIHEIQ RFGDMLPMGL AHRVNKDTKF RDFFLPKGTE VFPMLGSVLR
    410 420 430 440 450
    DPRFFSNPRD FNPQHFLDKK GQFKKSDAFV PFSIGKRYCF GEGLARMELF
    460 470 480 490
    LFFTTIMQNF RFKSPQSPKD IDVSPKHVGF ATIPRNYTMS FLPR
    Length:494
    Mass (Da):56,688
    Last modified:October 11, 2005 - v3
    Checksum:iA39F18AD71C28821
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti208 – 2081S → R in AAB40519 (PubMed:7668294).Curated
    Sequence conflicti213 – 2131A → G in AAB40519 (PubMed:7668294).Curated
    Sequence conflicti398 – 3981V → E in AAB40519 (PubMed:7668294).Curated
    Sequence conflicti409 – 4124RDFN → QDCS in AAB40519 (PubMed:7668294).Curated
    Sequence conflicti419 – 4191K → E in AAB40519 (PubMed:7668294).Curated

    Polymorphismi

    The frequencies of the Cys-257 allele in white, black, Hispanic, and Asian individuals are 1.9%, 14.4%, 5.8%, and 7.7%, respectively. The Cys-257 variant is 37 to 56% less active than the wild-type Arg-257 protein toward all substrates tested.

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti25 – 251R → Q in allele CYP2A13*2. 2 Publications
    Corresponds to variant rs8192784 [ dbSNP | Ensembl ].
    VAR_018334
    Natural varianti101 – 1011R → Q in allele CYP2A13*4. 1 Publication
    VAR_018335
    Natural varianti134 – 1341T → TT in allele CYP2A13*3. 1 Publication
    VAR_018336
    Natural varianti158 – 1581D → E in allele CYP2A13*3 and allele CYP2A13*8. 2 Publications
    Corresponds to variant rs112337232 [ dbSNP | Ensembl ].
    VAR_018337
    Natural varianti257 – 2571R → C in allele CYP2A13*2. 2 Publications
    Corresponds to variant rs8192789 [ dbSNP | Ensembl ].
    VAR_013835
    Natural varianti323 – 3231V → L in allele CYP2A13*9. 1 Publication
    VAR_018356
    Natural varianti453 – 4531F → Y in allele CYP2A13*5. 1 Publication
    VAR_018338
    Natural varianti494 – 4941R → C in allele CYP2A13*6. 1 Publication
    Corresponds to variant rs138870349 [ dbSNP | Ensembl ].
    VAR_018339

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U22028 Genomic DNA. Translation: AAB40519.1.
    AF209774 mRNA. Translation: AAG35775.1.
    AY513604 mRNA. Translation: AAR90935.1.
    AY513605 mRNA. Translation: AAR90936.1.
    AY513606 mRNA. Translation: AAR90937.1.
    AY513608 mRNA. Translation: AAR90939.1.
    AY513609 mRNA. Translation: AAR90940.1.
    CCDSiCCDS12571.1.
    PIRiI38966.
    RefSeqiNP_000757.2. NM_000766.4.
    UniGeneiHs.567252.

    Genome annotation databases

    EnsembliENST00000330436; ENSP00000332679; ENSG00000197838.
    GeneIDi1553.
    KEGGihsa:1553.
    UCSCiuc002opt.4. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    Cytochrome P450 Allele Nomenclature Committee

    CYP2A13 alleles

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    U22028 Genomic DNA. Translation: AAB40519.1.
    AF209774 mRNA. Translation: AAG35775.1.
    AY513604 mRNA. Translation: AAR90935.1.
    AY513605 mRNA. Translation: AAR90936.1.
    AY513606 mRNA. Translation: AAR90937.1.
    AY513608 mRNA. Translation: AAR90939.1.
    AY513609 mRNA. Translation: AAR90940.1.
    CCDSiCCDS12571.1.
    PIRiI38966.
    RefSeqiNP_000757.2. NM_000766.4.
    UniGeneiHs.567252.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2P85X-ray2.35A/B/C/D/E/F26-494[»]
    2PG5X-ray1.95A/B/C/D31-494[»]
    2PG6X-ray2.53A/B/C/D31-494[»]
    2PG7X-ray2.80A/B/C/D31-494[»]
    3T3SX-ray3.00A/B/C/D/E/F/G/H31-494[»]
    4EJGX-ray2.50A/B/C/D/E/F/G/H31-494[»]
    4EJHX-ray2.35A/B/C/D/E/F/G/H31-494[»]
    4EJIX-ray2.10A31-494[»]
    ProteinModelPortaliQ16696.
    SMRiQ16696. Positions 31-494.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi107931. 1 interaction.
    STRINGi9606.ENSP00000332679.

    Chemistry

    BindingDBiQ16696.
    DrugBankiDB00553. Methoxsalen.
    DB00184. Nicotine.
    DB00624. Testosterone.

    PTM databases

    PhosphoSiteiQ16696.

    Polymorphism and mutation databases

    BioMutaiCYP2A13.
    DMDMi77416854.

    Proteomic databases

    PaxDbiQ16696.
    PRIDEiQ16696.

    Protocols and materials databases

    DNASUi1553.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000330436; ENSP00000332679; ENSG00000197838.
    GeneIDi1553.
    KEGGihsa:1553.
    UCSCiuc002opt.4. human.

    Organism-specific databases

    CTDi1553.
    GeneCardsiGC19P041594.
    HGNCiHGNC:2608. CYP2A13.
    HPAiHPA046713.
    HPA047262.
    MIMi608055. gene.
    neXtProtiNX_Q16696.
    PharmGKBiPA27101.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG2124.
    GeneTreeiENSGT00760000118775.
    HOGENOMiHOG000036992.
    HOVERGENiHBG015789.
    InParanoidiQ16696.
    KOiK17685.
    OMAiRGTHGAN.
    OrthoDBiEOG7RBZ85.
    PhylomeDBiQ16696.
    TreeFamiTF352043.

    Enzyme and pathway databases

    ReactomeiREACT_13543. Xenobiotics.
    REACT_13797. CYP2E1 reactions.
    REACT_13814. Fatty acids.
    REACT_264461. Aflatoxin activation and detoxification.
    SABIO-RKQ16696.

    Miscellaneous databases

    EvolutionaryTraceiQ16696.
    GeneWikiiCYP2A13.
    GenomeRNAii1553.
    NextBioi6417.
    PROiQ16696.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ16696.
    CleanExiHS_CYP2A13.
    GenevestigatoriQ16696.

    Family and domain databases

    Gene3Di1.10.630.10. 1 hit.
    InterProiIPR001128. Cyt_P450.
    IPR017972. Cyt_P450_CS.
    IPR002401. Cyt_P450_E_grp-I.
    IPR008067. Cyt_P450_E_grp-I_CYP2A-like.
    [Graphical view]
    PfamiPF00067. p450. 1 hit.
    [Graphical view]
    PRINTSiPR00463. EP450I.
    PR01684. EP450ICYP2A.
    PR00385. P450.
    SUPFAMiSSF48264. SSF48264. 1 hit.
    PROSITEiPS00086. CYTOCHROME_P450. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    1. "A genetic polymorphism in coumarin 7-hydroxylation: sequence of the human CYP2A genes and identification of variant CYP2A6 alleles."
      Fernandez-Salguero P., Hoffman S.M., Cholerton S., Mohrenweiser H., Raunio H., Rautio A., Pelkonen O., Huang J.D., Evans W.E., Idle J.R.
      Am. J. Hum. Genet. 57:651-660(1995) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    2. "Human cytochrome P450 CYP2A13: predominant expression in the respiratory tract and its high efficiency metabolic activation of a tobacco-specific carcinogen, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone."
      Su T., Bao Z., Zhang Q.Y., Smith T.J., Hong J.Y., Ding X.
      Cancer Res. 60:5074-5079(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, TISSUE SPECIFICITY.
    3. "Genetic polymorphism of the human cytochrome CYP2A13 in a French population: implication in lung cancer susceptibility."
      Cauffiez C., Lo-Guidice J.-M., Quaranta S., Allorge D., Chevalier D., Cenee S., Hamdan R., Lhermitte M., Lafitte J.-J., Libersa C., Colombel J.-F., Stuecker I., Broly F.
      Biochem. Biophys. Res. Commun. 317:662-669(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS GLU-158 AND LEU-323.
    4. "Key residues controlling phenacetin metabolism by human cytochrome P450 2A enzymes."
      DeVore N.M., Smith B.D., Urban M.J., Scott E.E.
      Drug Metab. Dispos. 36:2582-2590(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF LEU-110; ALA-117; SER-208; ALA-213; PHE-300; ALA-301; MET-365; LEU-366; GLY-369 AND HIS-372.
    5. "Structural insight into the altered substrate specificity of human cytochrome P450 2A6 mutants."
      Sansen S., Hsu M.H., Stout C.D., Johnson E.F.
      Arch. Biochem. Biophys. 464:197-206(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (1.95 ANGSTROMS) OF 29-494 IN COMPLEX WITH HEME.
    6. Cited for: X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 31-494 IN COMPLEX WITH SUBSTRATE ANALOG AND HEME.
    7. "Genetic polymorphisms of the human CYP2A13 gene: identification of single-nucleotide polymorphisms and functional characterization of an Arg257Cys variant."
      Zhang X., Su T., Zhang Q.Y., Gu J., Caggana M., Li H., Ding X.
      J. Pharmacol. Exp. Ther. 302:416-423(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CYS-257.
    8. Cited for: VARIANTS GLN-25; GLN-101; THR-134 INS; GLU-158; TYR-453 AND CYS-494.
    9. "Catalog of 680 variations among eight cytochrome p450 (CYP) genes, nine esterase genes, and two other genes in the Japanese population."
      Saito S., Iida A., Sekine A., Kawauchi S., Higuchi S., Ogawa C., Nakamura Y.
      J. Hum. Genet. 48:249-270(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS GLN-25 AND CYS-257.

    Entry informationi

    Entry nameiCP2AD_HUMAN
    AccessioniPrimary (citable) accession number: Q16696
    Secondary accession number(s): Q53YR8
    , Q6R569, Q6R570, Q9H2X2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: December 15, 1998
    Last sequence update: October 11, 2005
    Last modified: April 29, 2015
    This is version 145 of the entry and version 3 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

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 19
      Human chromosome 19: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. 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.