Q16696 (CP2AD_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cytochrome P450 2A13
EC=1.14.14.1

Alternative name(s):
CYPIIA13

Gene names

Name:

CYP2A13

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	494 AA.
Sequence status	Complete.
Protein existence	Evidence 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

Keywords
Cellular component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Polymorphism
Ligand	Heme Iron Metal-binding
Molecular function	Monooxygenase Oxidoreductase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	small molecule metabolic process Traceable author statement. Source: Reactome xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular_component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome
Molecular_function	aromatase activity Inferred from electronic annotation. Source: EC electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred from direct assay Ref.6. Source: UniProtKB iron ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 494

494

Cytochrome P450 2A13

PRO_0000051676

Sites

Metal binding

439

1

Iron (heme axial ligand)

Binding site

297

1

Substrate

Natural variations

Natural variant

25

1

R → Q in allele CYP2A13*2. Ref.8 Ref.9
Corresponds to variant rs8192784 [ dbSNP | Ensembl ].

VAR_018334

Natural variant

101

1

R → Q in allele CYP2A13*4. Ref.8

VAR_018335

Natural variant

134

1

T → TT in allele CYP2A13*3. Ref.8

VAR_018336

Natural variant

158

1

D → E in allele CYP2A13*3 and allele CYP2A13*8. Ref.3 Ref.8

VAR_018337

Natural variant

257

1

R → C in allele CYP2A13*2. Ref.7 Ref.9
Corresponds to variant rs8192789 [ dbSNP | Ensembl ].

VAR_013835

Natural variant

323

1

V → L in allele CYP2A13*9. Ref.3

VAR_018356

Natural variant

453

1

F → Y in allele CYP2A13*5. Ref.8

VAR_018338

Natural variant

494

1

R → C in allele CYP2A13*6. Ref.8

VAR_018339

Experimental info

Mutagenesis

110

1

L → V: Decreases phenacetin O-deethylation activity 8 fold. Ref.4

Mutagenesis

117

1

A → V: Increases phenacetin O-deethylation activity 5 fold. Ref.4

Mutagenesis

208

1

S → I: Decreases phenacetin O-deethylation activity 10 fold. Ref.4

Mutagenesis

213

1

A → S: Decreases phenacetin O-deethylation activity 2 fold. Ref.4

Mutagenesis

300

1

F → I: Decreases phenacetin O-deethylation activity 40 fold. Ref.4

Mutagenesis

301

1

A → G: Decreases phenacetin O-deethylation activity 20 fold. Ref.4

Mutagenesis

365

1

M → V: Decreases phenacetin O-deethylation activity 7 fold. Ref.4

Mutagenesis

366

1

L → I: Increases phenacetin O-deethylation activity 3 fold. Ref.4

Mutagenesis

369

1

G → S: Decreases phenacetin O-deethylation activity 9 fold. Ref.4

Mutagenesis

372

1

H → R: Decreases phenacetin O-deethylation activity 3 fold. Ref.4

Sequence conflict

208

1

S → R in AAB40519. Ref.1

Sequence conflict

213

1

A → G in AAB40519. Ref.1

Sequence conflict

398

1

V → E in AAB40519. Ref.1

Sequence conflict

409 – 412

4

RDFN → QDCS in AAB40519. Ref.1

Sequence conflict

419

1

K → E in AAB40519. Ref.1

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

494

Helix Strand Turn

Details...

Turn

41 – 43

3

Helix

46 – 48

3

Helix

51 – 53

3

Helix

54 – 65

12

Beta strand

67 – 73

7

Beta strand

76 – 81

6

Helix

84 – 91

8

Turn

92 – 98

7

Helix

105 – 111

7

Turn

116 – 118

3

Helix

121 – 137

17

Turn

138 – 141

4

Helix

143 – 161

19

Turn

162 – 165

4

Helix

171 – 187

17

Helix

196 – 212

17

Helix

215 – 227

13

Beta strand

230 – 232

3

Helix

233 – 256

24

Helix

267 – 277

11

Turn

278 – 280

3

Helix

288 – 319

32

Helix

321 – 334

14

Beta strand

337 – 339

3

Helix

343 – 348

6

Helix

350 – 363

14

Beta strand

378 – 380

3

Beta strand

383 – 385

3

Beta strand

390 – 393

4

Helix

395 – 399

5

Turn

402 – 404

3

Helix

413 – 416

4

Beta strand

419 – 421

3

Helix

442 – 459

18

Beta strand

460 – 466

7

Helix

468 – 470

3

Beta strand

476 – 483

8

Beta strand

489 – 493

5

Sequences

	Sequence		Length	Mass (Da)
	Q16696 [UniParc]. Last modified October 11, 2005. Version 3. Checksum: A39F18AD71C28821	FASTA	494	56,688
	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

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.

Web resources

Cytochrome P450 Allele Nomenclature Committee

CYP2A13 alleles

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.

IPI

IPI00003480.

PIR

I38966.

RefSeq

NP_000757.2. NM_000766.4.

UniGene

Hs.567252.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2P85	X-ray	2.35	A/B/C/D/E/F	31-494	[»]
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	[»]

ProteinModelPortal

Q16696.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000332679.

PTM databases

PhosphoSite

Q16696.

Polymorphism databases

DMDM

77416854.

Proteomic databases

PaxDb

Q16696.

PRIDE

Q16696.

Protocols and materials databases

DNASU

1553.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000330436; ENSP00000332679; ENSG00000197838.

GeneID

1553.

KEGG

hsa:1553.

UCSC

uc002opt.3. human.

Organism-specific databases

CTD

1553.

GeneCards

GC19P041594.

HGNC

HGNC:2608. CYP2A13.

MIM

608055. gene.

neXtProt

NX_Q16696.

PharmGKB

PA27101.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2124.

HOGENOM

HOG000036992.

HOVERGEN

HBG015789.

InParanoid

Q16696.

KO

K07411.

OMA

MYSSLMK.

OrthoDB

EOG4BP1BN.

PhylomeDB

Q16696.

Enzyme and pathway databases

Reactome

REACT_111217. Metabolism.

Gene expression databases

Bgee

Q16696.

CleanEx

HS_CYP2A13.

Genevestigator

Q16696.

GermOnline

ENSG00000197838. Homo sapiens.

Family and domain databases

Gene3D

1.10.630.10. 1 hit.

InterPro

IPR001128. Cyt_P450.
IPR017972. Cyt_P450_CS.
IPR002401. Cyt_P450_E_grp-I.
IPR008067. Cyt_P450_E_grp-I_CYP2A-like.
[Graphical view]

Pfam

PF00067. p450. 1 hit.
[Graphical view]

PRINTS

PR00463. EP450I.
PR01684. EP450ICYP2A.
PR00385. P450.

SUPFAM

SSF48264. Cytochrome_P450. 1 hit.

PROSITE

PS00086. CYTOCHROME_P450. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q16696.

DrugBank

DB01242. Clomipramine.
DB00184. Nicotine.

EvolutionaryTrace

Q16696.

GenomeRNAi

1553.

NextBio

6417.

SOURCE

Search...

Entry information

Entry name

CP2AD_HUMAN

Accession

Primary (citable) accession number: Q16696
Secondary accession number(s): Q53YR8 , Q6R569, Q6R570, Q9H2X2

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 15, 1998
Last sequence update:	October 11, 2005
Last modified:	May 1, 2013
This is version 127 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.