P20815 (CP3A5_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cytochrome P450 3A5
EC=1.14.14.1

Alternative name(s):
CYPIIIA5
Cytochrome P450 HLp2
Cytochrome P450-PCN3

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.
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.
Miscellaneous	Chimeric transcripts, characterized by CYP3A43 exon 1 joined at canonical splice sites to distinct sets of CYP3A5 exons, have been detected. All are possibly produced by trans-splicing. The chimeric transcripts exist in 2 different combinations: CYP3A43 exon 1 joined in frame to CYP3A5 exon 11-13 and CYP3A43 exon 1 joined in frame to CYP3A5 exon 12-13. All chimeric transcripts are expressed at very low levels in the liver (Ref.10).
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
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	alkaloid catabolic process Inferred from direct assay. Source: BHF-UCL drug catabolic process Inferred from direct assay. Source: BHF-UCL oxidative demethylation Inferred from direct assay. Source: BHF-UCL steroid metabolic process Traceable author statement. Source: ProtInc xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome microsome 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 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. Ref.13 Corresponds to variant rs55817950 [ dbSNP | Ensembl ].		VAR_024731
	Natural variant	30	1	H → Y. Ref.14 Corresponds to variant rs28383468 [ dbSNP | Ensembl ].		VAR_024728
	Natural variant	200	1	Q → R in allele CYP3A5*4. Ref.12 Corresponds to variant rs56411402 [ dbSNP | Ensembl ].		VAR_024732
	Natural variant	277	1	D → E. Ref.14 Corresponds to variant rs28383477 [ dbSNP | Ensembl ].		VAR_024729
	Natural variant	337	1	A → T in allele CYP3A5*9. Ref.13 Ref.14 Corresponds to variant rs28383479 [ dbSNP | Ensembl ].		VAR_024730
	Natural variant	371	1	I → V. Corresponds to variant rs28365092 [ dbSNP | Ensembl ].		VAR_029161
	Natural variant	398	1	T → N in allele CYP3A5*2. Ref.11 Ref.14 Corresponds to variant rs28365083 [ dbSNP | Ensembl ].		VAR_008365
	Natural variant	446	1	F → S. Ref.13 Corresponds to variant rs41279854 [ dbSNP | Ensembl ].		VAR_024733
	Natural variant	488	1	I → T. Corresponds to variant rs28365085 [ dbSNP | Ensembl ].		VAR_029162
Experimental info
	Sequence conflict	305	1	A → P no nucleotide entry Ref.2
	Sequence conflict	318	1	L → F no nucleotide entry Ref.2
	Sequence conflict	324	1	H → D no nucleotide entry Ref.2
	Sequence conflict	377	1	C → G no nucleotide entry Ref.2

Sequences

	Sequence		Length	Mass (Da)
	P20815 [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]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed: 12690205] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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].
[6]	"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.
[7]	"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.
[8]	"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.
[9]	"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.
[10]	"Intergenic mRNA molecules resulting from trans-splicing." Finta C., Zaphiropoulos P.G. J. Biol. Chem. 277:5882-5890(2002) [PubMed: 11726664] [Abstract] Cited for: TRANS-SPLICING.
[11]	"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.
[12]	"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.
[13]	"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.
[14]	"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
EMBL GenBank DDBJ	J04813 mRNA. Translation: AAA02993.1. AC005020 Genomic DNA. Translation: AAS02016.1. CH236956 Genomic DNA. Translation: EAL23868.1. CH471091 Genomic DNA. Translation: EAW76638.1. 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. NM_000777.3.
UniGene	Hs.571258.
3D structure databases
ProteinModelPortal	P20815.
SMR	P20815. Positions 30-495.
ModBase	Search...
Protein-protein interaction databases
IntAct	P20815. 3 interactions.
STRING	P20815.
PTM databases
PhosphoSite	P20815.
Polymorphism databases
DMDM	117157.
Proteomic databases
PRIDE	P20815.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000222982; ENSP00000222982; ENSG00000106258.
GeneID	1577.
KEGG	hsa:1577.
UCSC	uc003urq.1. human.
Organism-specific databases
CTD	1577.
GeneCards	GC07M099246.
H-InvDB	HIX0006899.
HGNC	HGNC:2638. CYP3A5.
MIM	605325. gene.
neXtProt	NX_P20815.
Orphanet	240945. Resistance to tacrolimus in transplantation. 241043. Tacrolimus dose selection in transplantation.
PharmGKB	PA131.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG716150.
HOVERGEN	HBG108567.
InParanoid	P20815.
OMA	PTYDAVV.
OrthoDB	EOG4ZW59X.
PhylomeDB	P20815.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	P20815.
Bgee	P20815.
CleanEx	HS_CYP3A5.
Genevestigator	P20815.
GermOnline	ENSG00000106258. Homo sapiens.
Family and domain databases
InterPro	IPR001128. Cyt_P450. 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.
KO	K07424.
Pfam	PF00067. p450. 1 hit. [Graphical view]
PRINTS	PR00464. EP450II. PR01689. EP450IICYP3A. PR00385. P450.
SUPFAM	SSF48264. Cytochrome_P450. 1 hit.
PROSITE	PS00086. CYTOCHROME_P450. 1 hit. [Graphical view]
ProtoNet	Search...
Other
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): A4D289 , Q53WY8, Q75MV0, Q9HB56

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	February 1, 1991
Last modified:	January 25, 2012
This is version 125 of the entry and version 1 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.