Reviewed, UniProtKB/Swiss-Prot P20815 (CP3A5_HUMAN)

Names and origin

Protein names

Recommended name:
    Cytochrome P450 3A5
    EC=1.14.14.1
Alternative name(s):
    CYPIIIA5
    P450-PCN3
    HLp2

Gene names

Name:

CYP3A5

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	502 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics.
Catalytic activity	RH + reduced flavoprotein + O2 = ROH + oxidized flavoprotein + H2O.
Cofactor	Heme group By similarity.
Subcellular location	Endoplasmic reticulum membrane; Peripheral membrane protein. Microsome membrane; Peripheral membrane protein.
Induction	P450 can be induced to high levels in liver and other tissues by various foreign compounds, including drugs, pesticides, and carcinogens.
Sequence similarities	Belongs to the cytochrome P450 family.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Polymorphism
Ligand	Heme Iron Metal-binding
Molecular function	Monooxygenase Oxidoreductase
Gene Ontology (GO)
Biological process	oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW steroid metabolic process Ref.1 Traceable author statement. Source: ProtInc
Cellular component	endoplasmic reticulum membrane Inferred from electronic annotation. Source: UniProtKB-SubCell microsome Ref.1 Traceable author statement. Source: ProtInc
Molecular function	aromatase activity Inferred from electronic annotation. Source: EC electron carrier activity Inferred from electronic annotation. Source: InterPro heme binding Inferred from electronic annotation. Source: InterPro oxygen binding Ref.1 Traceable author statement. Source: ProtInc
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 502	502	Cytochrome P450 3A5		PRO_0000051787
Sites
	Metal binding	441	1	Iron (heme axial ligand)
Natural variations
	Natural variant	28	1	R → C in allele CYP3A5*8. dbSNP rs55817950. Ref.10		VAR_024731
	Natural variant	30	1	H → Y: dbSNP rs28383468. Ref.11		VAR_024728
	Natural variant	200	1	Q → R in allele CYP3A5*4. dbSNP rs56411402. Ref.9		VAR_024732
	Natural variant	277	1	D → E: dbSNP rs28383477. Ref.11		VAR_024729
	Natural variant	337	1	A → T in allele CYP3A5*9. dbSNP rs28383479. Ref.10 Ref.11		VAR_024730
	Natural variant	371	1	I → V: dbSNP rs28365092.		VAR_029161
	Natural variant	398	1	T → N in allele CYP3A5*2. dbSNP rs28365083. Ref.11 Ref.8		VAR_008365
	Natural variant	446	1	F → S: dbSNP rs41279854. Ref.10		VAR_024733
	Natural variant	488	1	I → T: dbSNP rs28365085.		VAR_029162
Experimental info
	Sequence conflict	305	1	A → P Ref.2
	Sequence conflict	318	1	L → F Ref.2
	Sequence conflict	324	1	H → D Ref.2
	Sequence conflict	377	1	C → G Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P20815-1 [UniParc]. Last modified February 1, 1991. Version 1. Checksum: D5A2302E2633E717	FASTA	502	57,109
	10 20 30 40 50 60 MDLIPNLAVE TWLLLAVSLV LLYLYGTRTH GLFKRLGIPG PTPLPLLGNV LSYRQGLWKF 70 80 90 100 110 120 DTECYKKYGK MWGTYEGQLP VLAITDPDVI RTVLVKECYS VFTNRRSLGP VGFMKSAISL 130 140 150 160 170 180 AEDEEWKRIR SLLSPTFTSG KLKEMFPIIA QYGDVLVRNL RREAEKGKPV TLKDIFGAYS 190 200 210 220 230 240 MDVITGTSFG VNIDSLNNPQ DPFVESTKKF LKFGFLDPLF LSIILFPFLT PVFEALNVSL 250 260 270 280 290 300 FPKDTINFLS KSVNRMKKSR LNDKQKHRLD FLQLMIDSQN SKETESHKAL SDLELAAQSI 310 320 330 340 350 360 IFIFAGYETT SSVLSFTLYE LATHPDVQQK LQKEIDAVLP NKAPPTYDAV VQMEYLDMVV 370 380 390 400 410 420 NETLRLFPVA IRLERTCKKD VEINGVFIPK GSMVVIPTYA LHHDPKYWTE PEEFRPERFS 430 440 450 460 470 480 KKKDSIDPYI YTPFGTGPRN CIGMRFALMN MKLALIRVLQ NFSFKPCKET QIPLKLDTQG 490 500 LLQPEKPIVL KVDSRDGTLS GE

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cytochrome P-450 hPCN3, a novel cytochrome P-450 IIIA gene product that is differentially expressed in adult human liver. cDNA and deduced amino acid sequence and distinct specificities of cDNA-expressed hPCN1 and hPCN3 for the metabolism of steroid hormones and cyclosporine." Aoyama T., Yamano S., Waxman D.J., Lapenson D.P., Meyer U.A., Fischer V., Tyndale R., Inaba T., Kalow W., Gelboin H.V., Gonzalez F.J. J. Biol. Chem. 264:10388-10395(1989) [PubMed: 2732228] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Characterization of a cDNA encoding a new member of the glucocorticoid-responsive cytochromes P450 in human liver." Schuetz J.D., Molowa D.T., Guzelian P.S. Arch. Biochem. Biophys. 274:355-365(1989) [PubMed: 2802615] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION. Tissue: Liver.
[3]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed: 12853948] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon.
[5]	"Genomic organization of the human CYP3A locus: identification of a new, inducible CYP3A gene." Gellner K., Eiselt R., Hustert E., Arnold H., Koch I., Haberl M., Deglmann C.J., Burk O., Buntefuss D., Escher S., Bishop C., Koebe H.-G., Brinkmann U., Klenk H.-P., Kleine K., Meyer U.A., Wojnowski L. Pharmacogenetics 11:111-121(2001) [PubMed: 11266076] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-106.
[6]	"Identification of a novel dexamethasone responsive enhancer in the human CYP3A5 gene and its activation in human and rat liver cells." Schuetz J.D., Schuetz E.G., Thottassery J.V., Guzelian P.S., Strom S., Sun D. Mol. Pharmacol. 49:63-72(1996) [PubMed: 8569713] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-24.
[7]	"Sequence of the 5'-flanking region of CYP3A5: comparative analysis with CYP3A4 and CYP3A7." Jounaidi Y., Guzelian P.S., Maurel P., Vilarem M.J. Biochem. Biophys. Res. Commun. 205:1741-1747(1994) [PubMed: 7811260] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-24.
[8]	"Detection of CYP3A5 allelic variant: a candidate for the polymorphic expression of the protein?" Jounaidi Y., Hyrailles V., Gervot L., Maurel P. Biochem. Biophys. Res. Commun. 221:466-470(1996) [PubMed: 8619878] [Abstract] Cited for: VARIANT CYP3A5*2 ASN-398.
[9]	"Genetic polymorphism of cytochrome P450 3A5 in Chinese." Chou F.C., Tzeng S.J., Huang J.D. Drug Metab. Dispos. 29:1205-1209(2001) [PubMed: 11502729] [Abstract] Cited for: VARIANT CYP3A5*4 ARG-200.
[10]	"Genetic findings and functional studies of human CYP3A5 single nucleotide polymorphisms in different ethnic groups." Lee S.J., Usmani K.A., Chanas B., Ghanayem B., Xi T., Hodgson E., Mohrenweiser H.W., Goldstein J.A. Pharmacogenetics 13:461-472(2003) [PubMed: 12893984] [Abstract] Cited for: VARIANTS CYS-28; THR-337 AND SER-446.
[11]	"Genetic variation in eleven phase I drug metabolism genes in an ethnically diverse population." Solus J.F., Arietta B.J., Harris J.R., Sexton D.P., Steward J.Q., McMunn C., Ihrie P., Mehall J.M., Edwards T.L., Dawson E.P. Pharmacogenomics 5:895-931(2004) [PubMed: 15469410] [Abstract] Cited for: VARIANTS TYR-30; GLU-277; THR-337 AND ASN-398.
+	Additional computationally mapped references.

Web resources

Cytochrome P450 Allele Nomenclature Committee

CYP3A5 alleles

Cross-references

Sequence databases
EMBLGenBankDDBJ	J04813 mRNA. Translation: AAA02993.1. AC005020 Genomic DNA. Translation: AAS02016.1. BC033862 mRNA. Translation: AAH33862.1. AF280107 Genomic DNA. Translation: AAG32288.1. L35912 Genomic DNA. Translation: AAB00083.1. S74699 Genomic DNA. Translation: AAD14157.1. S74700 Genomic DNA. Translation: AAD14158.1.
IPI	IPI00025831.
PIR	A34101. A60558.
RefSeq	NP_000768.1.
UniGene	Hs.695915
3D structure databases
HSSP	HSSP built from PDB template 1JPZ based on UniProtKB P14779.
SMR	P20815. Positions 29-498.
ModBase	Search...
PTM databases
PhosphoSite	P20815.
Proteomic databases
PRIDE	P20815.
Genome annotation databases
Ensembl	ENSG00000106258. Homo sapiens. [Contig view]
GeneID	1577.
KEGG	hsa:1577.
Organism-specific databases
GeneCards	GC07M099083.
H-InvDB	HIX0006899. HIX0034159.
HGNC	HGNC:2638. CYP3A5.
MIM	605325. gene.
PharmGKB	PA131.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	P20815.
HOVERGEN	P20815.
OMA	P20815. KFDTECY.
Enzyme and pathway databases
BRENDA	1.14.14.1. 247.
Reactome	REACT_13433. Biological oxidations.
Gene expression databases
ArrayExpress	P20815.
Bgee	P20815.
CleanEx	HS_CYP3A5.
GermOnline	ENSG00000106258. Homo sapiens.
Family and domain databases
InterPro	IPR001128. Cyt_P450. IPR017973. Cyt_P450_C. IPR017972. Cyt_P450_CS. IPR008072. Cyt_P450_E_CYP3A. IPR002402. Cyt_P450_E_grp-II. [Graphical view]
Gene3D	G3DSA:1.10.630.10. Cyt_P450. 1 hit.
PANTHER	PTHR19383. Cyt_P450. 1 hit.
Pfam	PF00067. p450. 1 hit. [Graphical view]
PRINTS	PR00464. EP450II. PR01689. EP450IICYP3A. PR00385. P450.
PROSITE	PS00086. CYTOCHROME_P450. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
DrugBank	DB00802. Alfentanil. DB00758. Clopidogrel. DB00091. Cyclosporine. DB00694. Daunorubicin. DB00224. Indinavir. DB00762. Irinotecan. DB01026. Ketoconazole. DB01259. Lapatinib. DB00532. Mephenytoin. DB00683. Midazolam. DB00834. Mifepristone. DB00252. Phenytoin. DB00468. Quinine. DB01232. Saquinavir. DB00864. Tacrolimus. DB01361. Troleandomycin. DB00661. Verapamil. DB00541. Vincristine.
NextBio	6479.
SOURCE	Search...

Entry information

Entry name

CP3A5_HUMAN

Accession

Primary (citable) accession number: P20815
Secondary accession number(s): Q53WY8, Q75MV0, Q9HB56

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	February 1, 1991
Last modified:	May 5, 2009
This is version 101 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)