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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

  1. arachidonic acid epoxygenase activity Source: GO_Central
  2. aromatase activity Source: UniProtKB-EC
  3. heme binding Source: UniProtKB
  4. iron ion binding Source: InterPro
  5. oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen Source: GO_Central
  6. oxygen binding Source: GO_Central
  7. steroid hydroxylase activity Source: GO_Central

GO - Biological processi

  1. coumarin metabolic process Source: GO_Central
  2. epoxygenase P450 pathway Source: GO_Central
  3. exogenous drug catabolic process Source: GO_Central
  4. oxidation-reduction process Source: GO_Central
  5. small molecule metabolic process Source: Reactome
  6. xenobiotic metabolic process Source: GO_Central
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

  1. cytoplasm Source: GO_Central
  2. endoplasmic reticulum membrane Source: Reactome
  3. intracellular membrane-bounded organelle Source: GO_Central
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.

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

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.

Polymorphism databases

DMDMi77416854.

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

STRINGi9606.ENSP00000332679.

Chemistry

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

PTM databases

PhosphoSiteiQ16696.

Polymorphism databases

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(1994) [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(1999) [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(2003) [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(2007) [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(2006) [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(2001) [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(2002) [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 1, 2015
This is version 144 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.