Q9HB55 (CP343_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Cytochrome P450 3A43
EC=1.14.14.1

Gene names

Name:

CYP3A43

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	503 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Exhibits low testosterone 6-beta-hydroxylase activity.
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.
Tissue specificity	Highest expression level in prostate. Also expressed in liver, kidney, pancreas, fetal liver and fetal skeletal muscle. Ref.1 Ref.2
Induction	By rifampicin.
Polymorphism	At protein level, three alleles are known: CYP3A43*1, CYP3A43*2 and CYP3A43*3. The sequence shown is that of CYP3A43*1, which is the most frequent allele. The allele CYP3A43*2 is likely to be non-functional.
Miscellaneous	Chimeric transcripts, characterized by CYP3A43 exon 1 joined at canonical splice sites to distinct sets of CYP3A4 or CYP3A5 exons, have been detected. All are possibly produced by trans-splicing. CYP3A43-CYP3A4 chimeric transcripts exist in 3 different combinations: CYP3A43 exon 1 joined in frame to CYP3A4 exons 2-13, CYP3A43 exon 1 joined in frame to CYP3A4 exons 4-13 and CYP3A43 exon 1 joined in frame to CYP3A4 exon 7-13. The longest chimeric CYP3A43 exon 1 joined to CYP3A4 exons 2-13) exhibits 6-beta-hydroxylase activity, while a shorter CYP3A43 exon 1 joined to CYP3A4 exons 4-13) does not. CYP3A43-CYP3A5 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.5).
Sequence similarities	Belongs to the cytochrome P450 family.

Ontologies

Keywords
Cellular component	Endoplasmic reticulum Membrane Microsome
Coding sequence diversity	Alternative splicing Polymorphism
Ligand	Heme Iron Metal-binding
Molecular function	Monooxygenase Oxidoreductase
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	xenobiotic metabolic process Traceable author statement. Source: Reactome
Cellular component	endoplasmic reticulum membrane Traceable author statement. Source: Reactome microsome Inferred from electronic annotation. Source: UniProtKB-SubCell
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
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.

Isoform 1 (identifier: Q9HB55-1)

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: Q9HB55-2)

The sequence of this isoform differs from the canonical sequence as follows:
     417-417: E → ES

Isoform 3 (identifier: Q9HB55-3)

The sequence of this isoform differs from the canonical sequence as follows:
     419-420: FS → SH
     421-503: Missing.

Isoform 4 (identifier: Q9HB55-4)

The sequence of this isoform differs from the canonical sequence as follows:
     224-250: SLFPFLTPVFEALNIGLFPKDVTHFLK → YRVSLCCLGRSAWCDLGSLKPPPPGFE
     251-503: Missing.

Note: May be produced at very low levels due to a premature stop codon in the mRNA, leading to nonsense-mediated mRNA decay.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 503	503	Cytochrome P450 3A43		PRO_0000051814
Sites
	Metal binding	442	1	Iron (heme axial ligand) By similarity
Natural variations
	Alternative sequence	224 – 250	27	SLFPF…THFLK → YRVSLCCLGRSAWCDLGSLK PPPPGFE in isoform 4.		VSP_000612
	Alternative sequence	251 – 503	253	Missing in isoform 4.		VSP_000613
	Alternative sequence	417	1	E → ES in isoform 2.		VSP_000609
	Alternative sequence	419 – 420	2	FS → SH in isoform 3.		VSP_000610
	Alternative sequence	421 – 503	83	Missing in isoform 3.		VSP_000611
	Natural variant	25 – 88	64	YGTHS…IMDPD → LGPIHINFLRSWEFLGQPLC LFWELFCSTLGVFGILTENV MKNTEKCGGCMRGNSPCWSS WIPT in allele CYP3A43*2.		VAR_018050
	Natural variant	27	1	T → A. Corresponds to variant rs45558032 [ dbSNP | Ensembl ].		VAR_048449
	Natural variant	89 – 503	415	Missing in allele CYP3A43*2.		VAR_018051
	Natural variant	145	1	M → I. Corresponds to variant rs45450092 [ dbSNP | Ensembl ].		VAR_048450
	Natural variant	275	1	M → I. Corresponds to variant rs45621431 [ dbSNP | Ensembl ].		VAR_048451
	Natural variant	340	1	P → A in allele CYP3A43*3. Ref.4 Corresponds to variant rs680055 [ dbSNP | Ensembl ].		VAR_018052

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 2C585B9DC573F634	FASTA	503	57,670
	10 20 30 40 50 60 MDLIPNFAME TWVLVATSLV LLYIYGTHSH KLFKKLGIPG PTPLPFLGTI LFYLRGLWNF 70 80 90 100 110 120 DRECNEKYGE MWGLYEGQQP MLVIMDPDMI KTVLVKECYS VFTNQMPLGP MGFLKSALSF 130 140 150 160 170 180 AEDEEWKRIR TLLSPAFTSV KFKEMVPIIS QCGDMLVRSL RQEAENSKSI NLKDFFGAYT 190 200 210 220 230 240 MDVITGTLFG VNLDSLNNPQ DPFLKNMKKL LKLDFLDPFL LLISLFPFLT PVFEALNIGL 250 260 270 280 290 300 FPKDVTHFLK NSIERMKESR LKDKQKHRVD FFQQMIDSQN SKETKSHKAL SDLELVAQSI 310 320 330 340 350 360 IIIFAAYDTT STTLPFIMYE LATHPDVQQK LQEEIDAVLP NKAPVTYDAL VQMEYLDMVV 370 380 390 400 410 420 NETLRLFPVV SRVTRVCKKD IEINGVFIPK GLAVMVPIYA LHHDPKYWTE PEKFCPERFS 430 440 450 460 470 480 KKNKDSIDLY RYIPFGAGPR NCIGMRFALT NIKLAVIRAL QNFSFKPCKE TQIPLKLDNL 490 500 PILQPEKPIV LKVHLRDGIT SGP
	Isoform 2 [UniParc]. Checksum: CB87C6873DAB7B0D	FASTA	504	57,757
	10 20 30 40 50 60 MDLIPNFAME TWVLVATSLV LLYIYGTHSH KLFKKLGIPG PTPLPFLGTI LFYLRGLWNF 70 80 90 100 110 120 DRECNEKYGE MWGLYEGQQP MLVIMDPDMI KTVLVKECYS VFTNQMPLGP MGFLKSALSF 130 140 150 160 170 180 AEDEEWKRIR TLLSPAFTSV KFKEMVPIIS QCGDMLVRSL RQEAENSKSI NLKDFFGAYT 190 200 210 220 230 240 MDVITGTLFG VNLDSLNNPQ DPFLKNMKKL LKLDFLDPFL LLISLFPFLT PVFEALNIGL 250 260 270 280 290 300 FPKDVTHFLK NSIERMKESR LKDKQKHRVD FFQQMIDSQN SKETKSHKAL SDLELVAQSI 310 320 330 340 350 360 IIIFAAYDTT STTLPFIMYE LATHPDVQQK LQEEIDAVLP NKAPVTYDAL VQMEYLDMVV 370 380 390 400 410 420 NETLRLFPVV SRVTRVCKKD IEINGVFIPK GLAVMVPIYA LHHDPKYWTE PEKFCPESRF 430 440 450 460 470 480 SKKNKDSIDL YRYIPFGAGP RNCIGMRFAL TNIKLAVIRA LQNFSFKPCK ETQIPLKLDN 490 500 LPILQPEKPI VLKVHLRDGI TSGP
	Isoform 3 [UniParc]. Checksum: 60873437189BA207	FASTA	420	48,304
	10 20 30 40 50 60 MDLIPNFAME TWVLVATSLV LLYIYGTHSH KLFKKLGIPG PTPLPFLGTI LFYLRGLWNF 70 80 90 100 110 120 DRECNEKYGE MWGLYEGQQP MLVIMDPDMI KTVLVKECYS VFTNQMPLGP MGFLKSALSF 130 140 150 160 170 180 AEDEEWKRIR TLLSPAFTSV KFKEMVPIIS QCGDMLVRSL RQEAENSKSI NLKDFFGAYT 190 200 210 220 230 240 MDVITGTLFG VNLDSLNNPQ DPFLKNMKKL LKLDFLDPFL LLISLFPFLT PVFEALNIGL 250 260 270 280 290 300 FPKDVTHFLK NSIERMKESR LKDKQKHRVD FFQQMIDSQN SKETKSHKAL SDLELVAQSI 310 320 330 340 350 360 IIIFAAYDTT STTLPFIMYE LATHPDVQQK LQEEIDAVLP NKAPVTYDAL VQMEYLDMVV 370 380 390 400 410 420 NETLRLFPVV SRVTRVCKKD IEINGVFIPK GLAVMVPIYA LHHDPKYWTE PEKFCPERSH
	Isoform 4 [UniParc]. Checksum: 858527154F617A06	FASTA	250	28,490
	10 20 30 40 50 60 MDLIPNFAME TWVLVATSLV LLYIYGTHSH KLFKKLGIPG PTPLPFLGTI LFYLRGLWNF 70 80 90 100 110 120 DRECNEKYGE MWGLYEGQQP MLVIMDPDMI KTVLVKECYS VFTNQMPLGP MGFLKSALSF 130 140 150 160 170 180 AEDEEWKRIR TLLSPAFTSV KFKEMVPIIS QCGDMLVRSL RQEAENSKSI NLKDFFGAYT 190 200 210 220 230 240 MDVITGTLFG VNLDSLNNPQ DPFLKNMKKL LKLDFLDPFL LLIYRVSLCC LGRSAWCDLG 250 SLKPPPPGFE

References

[1]	"cDNA cloning and initial characterization of CYP3A43, a novel human cytochrome P450." Domanski T.L., Finta C., Halpert J.R., Zaphiropoulos P.G. Mol. Pharmacol. 59:386-392(2001) [PubMed: 11160876] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY, CHARACTERIZATION.
[2]	"Cloning and tissue distribution of a novel human cytochrome P450 of the CYP3A subfamily, CYP3A43." Westlind A., Malmebo S., Johansson I., Otter C., Andersson T.B., Ingelman-Sundberg M., Oscarson M. Biochem. Biophys. Res. Commun. 281:1349-1355(2001) [PubMed: 11243885] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[3]	"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 / MRNA], ALTERNATIVE SPLICING. Tissue: Liver.
[4]	"First report of a genetic polymorphism of the cytochrome P450 3A43 (CYP3A43) gene: identification of a loss-of-function variant." Cauffiez C., Lo-Guidice J.-M., Chevalier D., Allorge D., Hamdan R., Lhermitte M., Lafitte J.-J., Colombel J.-F., Libersa C., Broly F. Hum. Mutat. 23:101-101(2004) [PubMed: 14695544] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ALLELE CYP3A43*2), VARIANT CYP3A43*3 ALA-340.
[5]	"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.
[6]	"An unappreciated role for RNA surveillance." Hillman R.T., Green R.E., Brenner S.E. Genome Biol. 5:R8.1-R8.16(2004) [PubMed: 14759258] [Abstract] Cited for: SPLICE ISOFORM(S) THAT ARE POTENTIAL NMD TARGET(S).
+	Additional computationally mapped references.

Web resources

Cytochrome P450 Allele Nomenclature Committee

CYP3A43 alleles

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF319634 mRNA. Translation: AAK00325.1. AF337813 mRNA. Translation: AAK38841.1. AF280107 Genomic DNA. Translation: AAG32291.1. AF280108 mRNA. Translation: AAG33009.1. AF280109 mRNA. Translation: AAG33010.1. AF280110 mRNA. Translation: AAG33011.1. AF280111 mRNA. Translation: AAG33012.1. AY390423 mRNA. Translation: AAQ92351.1. AY390424 mRNA. Translation: AAQ92352.1. AY390425 mRNA. Translation: AAQ92353.1. AY390426 mRNA. Translation: AAQ92354.1.
IPI	IPI00072735. IPI00220495. IPI00220496. IPI00220497.
PIR	JC7627.
RefSeq	NP_073731.1. NM_022820.3. NP_476436.1. NM_057095.1. NP_476437.1. NM_057096.2.
UniGene	Hs.306220. Hs.571258. Hs.728751.
3D structure databases
ProteinModelPortal	Q9HB55.
SMR	Q9HB55. Positions 28-498.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9HB55.
PTM databases
PhosphoSite	Q9HB55.
Polymorphism databases
DMDM	20137481.
Proteomic databases
PRIDE	Q9HB55.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000354829; ENSP00000346887; ENSG00000021461.
GeneID	64816.
KEGG	hsa:64816.
UCSC	uc003urx.1. human. uc003ury.1. human. uc003urz.1. human.
Organism-specific databases
CTD	64816.
GeneCards	GC07P099426.
HGNC	HGNC:17450. CYP3A43.
MIM	606534. gene.
neXtProt	NX_Q9HB55.
GenAtlas	Search...
Phylogenomic databases
GeneTree	ENSGT00540000069787.
HOVERGEN	HBG108567.
OMA	CPESRFS.
OrthoDB	EOG4M65HF.
PhylomeDB	Q9HB55.
Enzyme and pathway databases
Reactome	REACT_111217. Metabolism.
Gene expression databases
ArrayExpress	Q9HB55.
Bgee	Q9HB55.
CleanEx	HS_CYP3A43.
Genevestigator	Q9HB55.
GermOnline	ENSG00000021461. 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	DB00341. Cetirizine. DB00254. Doxycycline.
NextBio	66908.
SOURCE	Search...

Entry information

Entry name

CP343_HUMAN

Accession

Primary (citable) accession number: Q9HB55
Secondary accession number(s): Q9HB52 , Q9HB53, Q9HB54, Q9HB57

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 31, 2002
Last sequence update:	March 1, 2001
Last modified:	January 25, 2012
This is version 104 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.