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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 NADPH--hemoprotein reductase] + O2 = ROH + [oxidized NADPH--hemoprotein reductase] + H2O.

Cofactori

Kineticsi

  1. KM=10.7 µM for phenacetin1 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei297Substrate1
    Metal bindingi439Iron (heme axial ligand)1

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Monooxygenase, Oxidoreductase

    Keywords - Ligandi

    Heme, Iron, Metal-binding

    Enzyme and pathway databases

    BioCyciZFISH:HS10333-MONOMER.
    ReactomeiR-HSA-211935. Fatty acids.
    R-HSA-211981. Xenobiotics.
    R-HSA-211999. CYP2E1 reactions.
    R-HSA-5423646. 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
    Proteomesi
    • UP000005640 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)DescriptionActionsGraphical viewLength
    Mutagenesisi110L → V: Decreases phenacetin O-deethylation activity 8 fold. 1 Publication1
    Mutagenesisi117A → V: Increases phenacetin O-deethylation activity 5 fold. 1 Publication1
    Mutagenesisi208S → I: Decreases phenacetin O-deethylation activity 10 fold. 1 Publication1
    Mutagenesisi213A → S: Decreases phenacetin O-deethylation activity 2 fold. 1 Publication1
    Mutagenesisi300F → I: Decreases phenacetin O-deethylation activity 40 fold. 1 Publication1
    Mutagenesisi301A → G: Decreases phenacetin O-deethylation activity 20 fold. 1 Publication1
    Mutagenesisi365M → V: Decreases phenacetin O-deethylation activity 7 fold. 1 Publication1
    Mutagenesisi366L → I: Increases phenacetin O-deethylation activity 3 fold. 1 Publication1
    Mutagenesisi369G → S: Decreases phenacetin O-deethylation activity 9 fold. 1 Publication1
    Mutagenesisi372H → R: Decreases phenacetin O-deethylation activity 3 fold. 1 Publication1

    Organism-specific databases

    DisGeNETi1553.
    OpenTargetsiENSG00000197838.
    PharmGKBiPA27101.

    Chemistry databases

    ChEMBLiCHEMBL3542436.
    DrugBankiDB00553. Methoxsalen.
    DB00184. Nicotine.
    DB00624. Testosterone.

    Polymorphism and mutation databases

    BioMutaiCYP2A13.
    DMDMi77416854.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00000516761 – 494Cytochrome P450 2A13Add BLAST494

    Proteomic databases

    EPDiQ16696.
    PaxDbiQ16696.
    PeptideAtlasiQ16696.
    PRIDEiQ16696.

    PTM databases

    iPTMnetiQ16696.
    PhosphoSitePlusiQ16696.

    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

    BgeeiENSG00000197838.
    CleanExiHS_CYP2A13.
    GenevisibleiQ16696. HS.

    Organism-specific databases

    HPAiHPA046713.
    HPA047262.

    Interactioni

    Protein-protein interaction databases

    BioGridi107931. 1 interactor.
    STRINGi9606.ENSP00000332679.

    Chemistry databases

    BindingDBiQ16696.

    Structurei

    Secondary structure

    1494
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Turni41 – 43Combined sources3
    Helixi46 – 48Combined sources3
    Helixi51 – 53Combined sources3
    Helixi54 – 65Combined sources12
    Beta strandi67 – 73Combined sources7
    Beta strandi76 – 81Combined sources6
    Helixi84 – 91Combined sources8
    Turni92 – 98Combined sources7
    Helixi105 – 111Combined sources7
    Turni116 – 118Combined sources3
    Helixi121 – 137Combined sources17
    Turni138 – 141Combined sources4
    Helixi143 – 161Combined sources19
    Turni162 – 165Combined sources4
    Helixi171 – 187Combined sources17
    Helixi196 – 212Combined sources17
    Helixi215 – 227Combined sources13
    Beta strandi230 – 232Combined sources3
    Helixi233 – 256Combined sources24
    Helixi267 – 277Combined sources11
    Turni278 – 280Combined sources3
    Helixi288 – 319Combined sources32
    Helixi321 – 334Combined sources14
    Beta strandi337 – 339Combined sources3
    Helixi343 – 348Combined sources6
    Helixi350 – 363Combined sources14
    Beta strandi378 – 380Combined sources3
    Beta strandi383 – 385Combined sources3
    Beta strandi390 – 393Combined sources4
    Helixi395 – 399Combined sources5
    Turni402 – 404Combined sources3
    Helixi413 – 416Combined sources4
    Beta strandi419 – 421Combined sources3
    Helixi442 – 459Combined sources18
    Beta strandi460 – 466Combined sources7
    Helixi468 – 470Combined sources3
    Beta strandi476 – 483Combined sources8
    Beta strandi489 – 493Combined sources5

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB 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.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ16696.

    Family & Domainsi

    Sequence similaritiesi

    Belongs to the cytochrome P450 family.Curated

    Phylogenomic databases

    eggNOGiKOG0156. Eukaryota.
    COG2124. LUCA.
    GeneTreeiENSGT00760000118775.
    HOGENOMiHOG000036992.
    HOVERGENiHBG015789.
    InParanoidiQ16696.
    KOiK17685.
    OMAiQFTSTSM.
    OrthoDBiEOG091G0BT8.
    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)DescriptionActionsGraphical viewLength
    Sequence conflicti208S → R in AAB40519 (PubMed:7668294).Curated1
    Sequence conflicti213A → G in AAB40519 (PubMed:7668294).Curated1
    Sequence conflicti398V → E in AAB40519 (PubMed:7668294).Curated1
    Sequence conflicti409 – 412RDFN → QDCS in AAB40519 (PubMed:7668294).Curated4
    Sequence conflicti419K → E in AAB40519 (PubMed:7668294).Curated1

    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)DescriptionActionsGraphical viewLength
    Natural variantiVAR_01833425R → Q in allele CYP2A13*2. 2 PublicationsCorresponds to variant rs8192784dbSNPEnsembl.1
    Natural variantiVAR_018335101R → Q in allele CYP2A13*4. 1 PublicationCorresponds to variant rs148044792dbSNPEnsembl.1
    Natural variantiVAR_018336134T → TT in allele CYP2A13*3. 1 Publication1
    Natural variantiVAR_018337158D → E in allele CYP2A13*3 and allele CYP2A13*8. 2 PublicationsCorresponds to variant rs112337232dbSNPEnsembl.1
    Natural variantiVAR_013835257R → C in allele CYP2A13*2. 2 PublicationsCorresponds to variant rs8192789dbSNPEnsembl.1
    Natural variantiVAR_018356323V → L in allele CYP2A13*9. 1 Publication1
    Natural variantiVAR_018338453F → Y in allele CYP2A13*5. 1 PublicationCorresponds to variant rs72547590dbSNPEnsembl.1
    Natural variantiVAR_018339494R → C in allele CYP2A13*6. 1 PublicationCorresponds to variant rs138870349dbSNPEnsembl.1

    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.5. 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
    PDB 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.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi107931. 1 interactor.
    STRINGi9606.ENSP00000332679.

    Chemistry databases

    BindingDBiQ16696.
    ChEMBLiCHEMBL3542436.
    DrugBankiDB00553. Methoxsalen.
    DB00184. Nicotine.
    DB00624. Testosterone.

    PTM databases

    iPTMnetiQ16696.
    PhosphoSitePlusiQ16696.

    Polymorphism and mutation databases

    BioMutaiCYP2A13.
    DMDMi77416854.

    Proteomic databases

    EPDiQ16696.
    PaxDbiQ16696.
    PeptideAtlasiQ16696.
    PRIDEiQ16696.

    Protocols and materials databases

    DNASUi1553.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000330436; ENSP00000332679; ENSG00000197838.
    GeneIDi1553.
    KEGGihsa:1553.
    UCSCiuc002opt.5. human.

    Organism-specific databases

    CTDi1553.
    DisGeNETi1553.
    GeneCardsiCYP2A13.
    HGNCiHGNC:2608. CYP2A13.
    HPAiHPA046713.
    HPA047262.
    MIMi608055. gene.
    neXtProtiNX_Q16696.
    OpenTargetsiENSG00000197838.
    PharmGKBiPA27101.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG0156. Eukaryota.
    COG2124. LUCA.
    GeneTreeiENSGT00760000118775.
    HOGENOMiHOG000036992.
    HOVERGENiHBG015789.
    InParanoidiQ16696.
    KOiK17685.
    OMAiQFTSTSM.
    OrthoDBiEOG091G0BT8.
    PhylomeDBiQ16696.
    TreeFamiTF352043.

    Enzyme and pathway databases

    BioCyciZFISH:HS10333-MONOMER.
    ReactomeiR-HSA-211935. Fatty acids.
    R-HSA-211981. Xenobiotics.
    R-HSA-211999. CYP2E1 reactions.
    R-HSA-5423646. Aflatoxin activation and detoxification.
    SABIO-RKQ16696.

    Miscellaneous databases

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

    Gene expression databases

    BgeeiENSG00000197838.
    CleanExiHS_CYP2A13.
    GenevisibleiQ16696. HS.

    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...

    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: November 2, 2016
    This is version 159 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

    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.