P20815 (CP3A5_HUMAN) Reviewed, UniProtKB/Swiss-Prot
Last modified
May 1, 2013.
Version 137.
History...
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order
Names·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize orderNames 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 |
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| Organism | Homo sapiens (Human) [Reference proteome] | ||
| 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.11). |
| Sequence similarities | Belongs to the cytochrome P450 family. |
Ontologies
Alternative products
| This entry describes 2 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: P20815-1) This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: P20815-2) The sequence of this isoform differs from the canonical sequence as follows: 107-140: SLGPVGFMKSAISLAEDEEWKRIRSLLSPTFTSG → ICATTSTIKMQTHSVTMWLPPAVLQSQHGVCLFL 141-502: Missing. | ||||||
| Note: No experimental confirmation available. |
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 | |||||||||
| Alternative sequence | 107 – 140 | 34 | SLGPV…TFTSG → ICATTSTIKMQTHSVTMWLP PAVLQSQHGVCLFL in isoform 2. | VSP_042734 | |||||
| Alternative sequence | 141 – 502 | 362 | Missing in isoform 2. | VSP_042735 | |||||
| Natural variant | 28 | 1 | R → C in allele CYP3A5*8. Ref.14 Corresponds to variant rs55817950 [ dbSNP | Ensembl ]. | VAR_024731 | |||||
| Natural variant | 30 | 1 | H → Y. Ref.15 Corresponds to variant rs28383468 [ dbSNP | Ensembl ]. | VAR_024728 | |||||
| Natural variant | 200 | 1 | Q → R in allele CYP3A5*4. Ref.13 Corresponds to variant rs56411402 [ dbSNP | Ensembl ]. | VAR_024732 | |||||
| Natural variant | 277 | 1 | D → E. Ref.15 Corresponds to variant rs28383477 [ dbSNP | Ensembl ]. | VAR_024729 | |||||
| Natural variant | 337 | 1 | A → T in allele CYP3A5*9. Ref.14 Ref.15 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.12 Ref.15 Corresponds to variant rs28365083 [ dbSNP | Ensembl ]. | VAR_008365 | |||||
| Natural variant | 446 | 1 | F → S. Ref.14 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
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References
| « Hide '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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION. Tissue: Liver. |
| [3] | "Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). |
| [4] | "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. Tsui L.-C.Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [5] | 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. Venter J.C.Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [6] | "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. Wilson R.K.Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [7] | "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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Colon. |
| [8] | "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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-106. |
| [9] | "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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-24. |
| [10] | "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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-24. |
| [11] | "Intergenic mRNA molecules resulting from trans-splicing." Finta C., Zaphiropoulos P.G. J. Biol. Chem. 277:5882-5890(2002) [PubMed] [Europe PMC] [Abstract] Cited for: TRANS-SPLICING. |
| [12] | "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] [Europe PMC] [Abstract] Cited for: VARIANT CYP3A5*2 ASN-398. |
| [13] | "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] [Europe PMC] [Abstract] Cited for: VARIANT CYP3A5*4 ARG-200. |
| [14] | "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] [Europe PMC] [Abstract] Cited for: VARIANTS CYS-28; THR-337 AND SER-446. |
| [15] | "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] [Europe PMC] [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. AK299002 mRNA. Translation: BAH12923.1. AC005020 Genomic DNA. Translation: AAS02016.1. CH236956 Genomic DNA. Translation: EAL23868.1. CH471091 Genomic DNA. Translation: EAW76638.1. CH471091 Genomic DNA. Translation: EAW76642.1. 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. IPI00922923. |
| PIR | A34101. A60558. |
| RefSeq | NP_000768.1. NM_000777.3. NP_001177413.1. NM_001190484.1. |
| UniGene | Hs.571258. |
3D structure databases | |
| ProteinModelPortal | P20815. |
| ModBase | Search... |
Protein-protein interaction databases | |
| IntAct | P20815. 4 interactions. |
| STRING | 9606.ENSP00000222982. |
PTM databases | |
| PhosphoSite | P20815. |
Polymorphism databases | |
| DMDM | 117157. |
Proteomic databases | |
| PaxDb | P20815. |
| PRIDE | P20815. |
Protocols and materials databases | |
| DNASU | 1577. |
| StructuralBiologyKnowledgebase | Search... |
Genome annotation databases | |
| Ensembl | ENST00000222982; ENSP00000222982; ENSG00000106258. ENST00000439761; ENSP00000401269; ENSG00000106258. |
| GeneID | 1577. |
| KEGG | hsa:1577. |
| UCSC | uc003urq.3. human. |
Organism-specific databases | |
| CTD | 1577. |
| GeneCards | GC07M099246. |
| 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 | |
| eggNOG | COG2124. |
| HOGENOM | HOG000082412. |
| HOVERGEN | HBG108567. |
| InParanoid | P20815. |
| KO | K07424. |
| OMA | PKDTINF. |
| OrthoDB | EOG4ZW59X. |
| PhylomeDB | P20815. |
Enzyme and pathway databases | |
| Reactome | REACT_111217. Metabolism. |
| SABIO-RK | P20815. |
Gene expression databases | |
| ArrayExpress | P20815. |
| Bgee | P20815. |
| CleanEx | HS_CYP3A5. |
| Genevestigator | P20815. |
| GermOnline | ENSG00000106258. Homo sapiens. |
Family and domain databases | |
| Gene3D | 1.10.630.10. 1 hit. |
| InterPro | IPR001128. Cyt_P450. IPR017972. Cyt_P450_CS. IPR008072. Cyt_P450_E_CYP3A. IPR002402. Cyt_P450_E_grp-II. [Graphical view] |
| 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 | |
| BindingDB | P20815. |
| ChEMBL | CHEMBL3019. |
| 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. |
| GenomeRNAi | 1577. |
| NextBio | 6479. |
| SOURCE | Search... |
Entry information
| Entry name | CP3A5_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P20815 Secondary accession number(s): A4D289 Q9HB56 | ||||||||
| Entry history |
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| 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. | ||||||||
Relevant documents
| Human chromosome 7 Human chromosome 7: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with
