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Q16696

- CP2AD_HUMAN

UniProt

Q16696 - CP2AD_HUMAN

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Protein

Cytochrome P450 2A13

Gene
CYP2A13
Organism
Homo sapiens (Human)
Status
Reviewed - 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

Heme group.

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. aromatase activity Source: UniProtKB-EC
  2. heme binding Source: UniProtKB
  3. iron ion binding Source: InterPro

GO - Biological processi

  1. small molecule metabolic process Source: Reactome
  2. xenobiotic metabolic process Source: Reactome
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.
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: Chromosome 19

Organism-specific databases

HGNCiHGNC:2608. CYP2A13.

Subcellular locationi

GO - Cellular componenti

  1. endoplasmic reticulum membrane Source: Reactome
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.

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 – 433
Helixi46 – 483
Helixi51 – 533
Helixi54 – 6512
Beta strandi67 – 737
Beta strandi76 – 816
Helixi84 – 918
Turni92 – 987
Helixi105 – 1117
Turni116 – 1183
Helixi121 – 13717
Turni138 – 1414
Helixi143 – 16119
Turni162 – 1654
Helixi171 – 18717
Helixi196 – 21217
Helixi215 – 22713
Beta strandi230 – 2323
Helixi233 – 25624
Helixi267 – 27711
Turni278 – 2803
Helixi288 – 31932
Helixi321 – 33414
Beta strandi337 – 3393
Helixi343 – 3486
Helixi350 – 36314
Beta strandi378 – 3803
Beta strandi383 – 3853
Beta strandi390 – 3934
Helixi395 – 3995
Turni402 – 4043
Helixi413 – 4164
Beta strandi419 – 4213
Helixi442 – 45918
Beta strandi460 – 4667
Helixi468 – 4703
Beta strandi476 – 4838
Beta strandi489 – 4935

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
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.

Miscellaneous databases

EvolutionaryTraceiQ16696.

Family & Domainsi

Sequence similaritiesi

Belongs to the cytochrome P450 family.

Phylogenomic databases

eggNOGiCOG2124.
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

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MLASGLLLVT LLACLTVMVL MSVWRQRKSR GKLPPGPTPL PFIGNYLQLN    50
TEQMYNSLMK ISERYGPVFT IHLGPRRVVV LCGHDAVKEA LVDQAEEFSG 100
RGEQATFDWL FKGYGVAFSN GERAKQLRRF SIATLRGFGV GKRGIEERIQ 150
EEAGFLIDAL RGTHGANIDP TFFLSRTVSN VISSIVFGDR FDYEDKEFLS 200
LLRMMLGSFQ FTATSTGQLY EMFSSVMKHL PGPQQQAFKE LQGLEDFIAK 250
KVEHNQRTLD PNSPRDFIDS FLIRMQEEEK NPNTEFYLKN LVMTTLNLFF 300
AGTETVSTTL RYGFLLLMKH PEVEAKVHEE IDRVIGKNRQ PKFEDRAKMP 350
YTEAVIHEIQ RFGDMLPMGL AHRVNKDTKF RDFFLPKGTE VFPMLGSVLR 400
DPRFFSNPRD FNPQHFLDKK GQFKKSDAFV PFSIGKRYCF GEGLARMELF 450
LFFTTIMQNF RFKSPQSPKD IDVSPKHVGF ATIPRNYTMS FLPR 494
Length:494
Mass (Da):56,688
Last modified:October 11, 2005 - v3
Checksum:iA39F18AD71C28821
GO

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 conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti208 – 2081S → R in AAB40519. 1 Publication
Sequence conflicti213 – 2131A → G in AAB40519. 1 Publication
Sequence conflicti398 – 3981V → E in AAB40519. 1 Publication
Sequence conflicti409 – 4124RDFN → QDCS in AAB40519. 1 Publication
Sequence conflicti419 – 4191K → E in AAB40519. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS12571.1.
PIRi I38966.
RefSeqi NP_000757.2. NM_000766.4.
UniGenei Hs.567252.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2P85 X-ray 2.35 A/B/C/D/E/F 26-494 [» ]
2PG5 X-ray 1.95 A/B/C/D 31-494 [» ]
2PG6 X-ray 2.53 A/B/C/D 31-494 [» ]
2PG7 X-ray 2.80 A/B/C/D 31-494 [» ]
3T3S X-ray 3.00 A/B/C/D/E/F/G/H 31-494 [» ]
4EJG X-ray 2.50 A/B/C/D/E/F/G/H 31-494 [» ]
4EJH X-ray 2.35 A/B/C/D/E/F/G/H 31-494 [» ]
4EJI X-ray 2.10 A 31-494 [» ]
ProteinModelPortali Q16696.
SMRi Q16696. Positions 31-494.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

STRINGi 9606.ENSP00000332679.

Chemistry

BindingDBi Q16696.
DrugBanki DB01242. Clomipramine.
DB00184. Nicotine.

PTM databases

PhosphoSitei Q16696.

Polymorphism databases

DMDMi 77416854.

Proteomic databases

PaxDbi Q16696.
PRIDEi Q16696.

Protocols and materials databases

DNASUi 1553.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000330436 ; ENSP00000332679 ; ENSG00000197838 .
GeneIDi 1553.
KEGGi hsa:1553.
UCSCi uc002opt.4. human.

Organism-specific databases

CTDi 1553.
GeneCardsi GC19P041594.
HGNCi HGNC:2608. CYP2A13.
MIMi 608055. gene.
neXtProti NX_Q16696.
PharmGKBi PA27101.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG2124.
HOGENOMi HOG000036992.
HOVERGENi HBG015789.
InParanoidi Q16696.
KOi K17685.
OMAi RGTHGAN.
OrthoDBi EOG7RBZ85.
PhylomeDBi Q16696.
TreeFami TF352043.

Enzyme and pathway databases

Reactomei REACT_13543. Xenobiotics.
REACT_13797. CYP2E1 reactions.
REACT_13814. Fatty acids.
SABIO-RK Q16696.

Miscellaneous databases

EvolutionaryTracei Q16696.
GeneWikii CYP2A13.
GenomeRNAii 1553.
NextBioi 6417.
PROi Q16696.
SOURCEi Search...

Gene expression databases

Bgeei Q16696.
CleanExi HS_CYP2A13.
Genevestigatori Q16696.

Family and domain databases

Gene3Di 1.10.630.10. 1 hit.
InterProi IPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
IPR008067. Cyt_P450_E_grp-I_CYP2A-like.
[Graphical view ]
Pfami PF00067. p450. 1 hit.
[Graphical view ]
PRINTSi PR00463. EP450I.
PR01684. EP450ICYP2A.
PR00385. P450.
SUPFAMi SSF48264. SSF48264. 1 hit.
PROSITEi PS00086. CYTOCHROME_P450. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: September 3, 2014
This is version 137 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

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