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Q16696 (CP2AD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 135. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Cytochrome P450 2A13

EC=1.14.14.1
Alternative name(s):
CYPIIA13
Gene names
Name:CYP2A13
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length494 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.4

Catalytic activity

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

Cofactor

Heme group.

Subcellular location

Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.

Tissue specificity

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. Ref.2

Polymorphism

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.

Sequence similarities

Belongs to the cytochrome P450 family.

Biophysicochemical properties

Kinetic parameters:

KM=10.7 µM for phenacetin Ref.4

Ontologies

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 494494Cytochrome P450 2A13
PRO_0000051676

Sites

Metal binding4391Iron (heme axial ligand)
Binding site2971Substrate

Natural variations

Natural variant251R → Q in allele CYP2A13*2. Ref.8 Ref.9
Corresponds to variant rs8192784 [ dbSNP | Ensembl ].
VAR_018334
Natural variant1011R → Q in allele CYP2A13*4. Ref.8
VAR_018335
Natural variant1341T → TT in allele CYP2A13*3. Ref.8
VAR_018336
Natural variant1581D → E in allele CYP2A13*3 and allele CYP2A13*8. Ref.3 Ref.8
Corresponds to variant rs112337232 [ dbSNP | Ensembl ].
VAR_018337
Natural variant2571R → C in allele CYP2A13*2. Ref.7 Ref.9
Corresponds to variant rs8192789 [ dbSNP | Ensembl ].
VAR_013835
Natural variant3231V → L in allele CYP2A13*9. Ref.3
VAR_018356
Natural variant4531F → Y in allele CYP2A13*5. Ref.8
VAR_018338
Natural variant4941R → C in allele CYP2A13*6. Ref.8
Corresponds to variant rs138870349 [ dbSNP | Ensembl ].
VAR_018339

Experimental info

Mutagenesis1101L → V: Decreases phenacetin O-deethylation activity 8 fold. Ref.4
Mutagenesis1171A → V: Increases phenacetin O-deethylation activity 5 fold. Ref.4
Mutagenesis2081S → I: Decreases phenacetin O-deethylation activity 10 fold. Ref.4
Mutagenesis2131A → S: Decreases phenacetin O-deethylation activity 2 fold. Ref.4
Mutagenesis3001F → I: Decreases phenacetin O-deethylation activity 40 fold. Ref.4
Mutagenesis3011A → G: Decreases phenacetin O-deethylation activity 20 fold. Ref.4
Mutagenesis3651M → V: Decreases phenacetin O-deethylation activity 7 fold. Ref.4
Mutagenesis3661L → I: Increases phenacetin O-deethylation activity 3 fold. Ref.4
Mutagenesis3691G → S: Decreases phenacetin O-deethylation activity 9 fold. Ref.4
Mutagenesis3721H → R: Decreases phenacetin O-deethylation activity 3 fold. Ref.4
Sequence conflict2081S → R in AAB40519. Ref.1
Sequence conflict2131A → G in AAB40519. Ref.1
Sequence conflict3981V → E in AAB40519. Ref.1
Sequence conflict409 – 4124RDFN → QDCS in AAB40519. Ref.1
Sequence conflict4191K → E in AAB40519. Ref.1

Secondary structure

...................................................................... 494
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q16696 [UniParc].

Last modified October 11, 2005. Version 3.
Checksum: A39F18AD71C28821

FASTA49456,688
        10         20         30         40         50         60 
MLASGLLLVT LLACLTVMVL MSVWRQRKSR GKLPPGPTPL PFIGNYLQLN TEQMYNSLMK 

        70         80         90        100        110        120 
ISERYGPVFT IHLGPRRVVV LCGHDAVKEA LVDQAEEFSG RGEQATFDWL FKGYGVAFSN 

       130        140        150        160        170        180 
GERAKQLRRF SIATLRGFGV GKRGIEERIQ EEAGFLIDAL RGTHGANIDP TFFLSRTVSN 

       190        200        210        220        230        240 
VISSIVFGDR FDYEDKEFLS LLRMMLGSFQ FTATSTGQLY EMFSSVMKHL PGPQQQAFKE 

       250        260        270        280        290        300 
LQGLEDFIAK KVEHNQRTLD PNSPRDFIDS FLIRMQEEEK NPNTEFYLKN LVMTTLNLFF 

       310        320        330        340        350        360 
AGTETVSTTL RYGFLLLMKH PEVEAKVHEE IDRVIGKNRQ PKFEDRAKMP YTEAVIHEIQ 

       370        380        390        400        410        420 
RFGDMLPMGL AHRVNKDTKF RDFFLPKGTE VFPMLGSVLR DPRFFSNPRD FNPQHFLDKK 

       430        440        450        460        470        480 
GQFKKSDAFV PFSIGKRYCF GEGLARMELF LFFTTIMQNF RFKSPQSPKD IDVSPKHVGF 

       490 
ATIPRNYTMS FLPR 

« Hide

References

[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]"Structure of the human lung cytochrome P450 2A13."
Smith B.D., Sanders J.L., Porubsky P.R., Lushington G.H., Stout C.D., Scott E.E.
J. Biol. Chem. 282:17306-17313(2007) [PubMed] [Europe PMC] [Abstract]
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]"Eighteen novel polymorphisms of the CYP2A13 gene in Japanese."
Fujieda M., Yamazaki H., Kiyotani K., Muroi A., Kunitoh H., Dosaka-Akita H., Sawamura Y., Kamataki T.
Drug Metab. Pharmacokinet. 18:86-90(2003) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRI38966.
RefSeqNP_000757.2. NM_000766.4.
UniGeneHs.567252.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2P85X-ray2.35A/B/C/D/E/F31-494[»]
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[»]
ProteinModelPortalQ16696.
SMRQ16696. Positions 31-494.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING9606.ENSP00000332679.

Chemistry

BindingDBQ16696.
DrugBankDB01242. Clomipramine.
DB00184. Nicotine.

PTM databases

PhosphoSiteQ16696.

Polymorphism databases

DMDM77416854.

Proteomic databases

PaxDbQ16696.
PRIDEQ16696.

Protocols and materials databases

DNASU1553.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000330436; ENSP00000332679; ENSG00000197838.
GeneID1553.
KEGGhsa:1553.
UCSCuc002opt.4. human.

Organism-specific databases

CTD1553.
GeneCardsGC19P041594.
HGNCHGNC:2608. CYP2A13.
MIM608055. gene.
neXtProtNX_Q16696.
PharmGKBPA27101.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2124.
HOGENOMHOG000036992.
HOVERGENHBG015789.
InParanoidQ16696.
KOK17685.
OMARGTHGAN.
OrthoDBEOG7RBZ85.
PhylomeDBQ16696.
TreeFamTF352043.

Enzyme and pathway databases

ReactomeREACT_111217. Metabolism.
SABIO-RKQ16696.

Gene expression databases

BgeeQ16696.
CleanExHS_CYP2A13.
GenevestigatorQ16696.

Family and domain databases

Gene3D1.10.630.10. 1 hit.
InterProIPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
IPR008067. Cyt_P450_E_grp-I_CYP2A-like.
[Graphical view]
PfamPF00067. p450. 1 hit.
[Graphical view]
PRINTSPR00463. EP450I.
PR01684. EP450ICYP2A.
PR00385. P450.
SUPFAMSSF48264. SSF48264. 1 hit.
PROSITEPS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ16696.
GeneWikiCYP2A13.
GenomeRNAi1553.
NextBio6417.
PROQ16696.
SOURCESearch...

Entry information

Entry nameCP2AD_HUMAN
AccessionPrimary (citable) accession number: Q16696
Secondary accession number(s): Q53YR8 expand/collapse secondary AC list , Q6R569, Q6R570, Q9H2X2
Entry history
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: October 11, 2005
Last modified: February 19, 2014
This is version 135 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM