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Protein

Cytochrome P450 3A43

Gene

CYP3A43

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Exhibits low testosterone 6-beta-hydroxylase activity.

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 isoform (CYP3A43 exon 1 joined to CYP3A4 exons 2-13) exhibits 6-beta-hydroxylase activity, while a shorter isoform (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 (PubMed:11726664).1 Publication

Catalytic activityi

RH + [reduced NADPH--hemoprotein reductase] + O2 = ROH + [oxidized NADPH--hemoprotein reductase] + H2O.

Cofactori

hemeBy similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi442Iron (heme axial ligand)By similarity1

GO - Molecular functioni

Keywordsi

Molecular functionMonooxygenase, Oxidoreductase
LigandHeme, Iron, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-211958 Miscellaneous substrates
R-HSA-211981 Xenobiotics

Names & Taxonomyi

Protein namesi
Recommended name:
Cytochrome P450 3A43 (EC:1.14.14.1)
Gene namesi
Name:CYP3A43
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000021461.16
HGNCiHGNC:17450 CYP3A43
MIMi606534 gene
neXtProtiNX_Q9HB55

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Endoplasmic reticulum, Membrane, Microsome

Pathology & Biotechi

Organism-specific databases

DisGeNETi64816
OpenTargetsiENSG00000021461
PharmGKBiPA427

Chemistry databases

ChEMBLiCHEMBL5792
DrugBankiDB05239 Cobimetinib
DB09102 Daclatasvir
DB01234 Dexamethasone
DB08930 Dolutegravir
DB00593 Ethosuximide
DB09048 Netupitant
DB00842 Oxazepam
DB00780 Phenelzine
DB01058 Praziquantel
DB01045 Rifampicin
DB01201 Rifapentine
DB00624 Testosterone
DB01361 Troleandomycin
DB00943 Zalcitabine

Polymorphism and mutation databases

BioMutaiCYP3A43
DMDMi20137481

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000518141 – 503Cytochrome P450 3A43Add BLAST503

Proteomic databases

PaxDbiQ9HB55
PeptideAtlasiQ9HB55
PRIDEiQ9HB55
ProteomicsDBi81485
81486 [Q9HB55-2]
81487 [Q9HB55-3]
81488 [Q9HB55-4]

PTM databases

iPTMnetiQ9HB55
PhosphoSitePlusiQ9HB55

Expressioni

Tissue specificityi

Highest expression level in prostate. Also expressed in liver, kidney, pancreas, fetal liver and fetal skeletal muscle.2 Publications

Inductioni

By rifampicin.

Gene expression databases

BgeeiENSG00000021461
CleanExiHS_CYP3A43
ExpressionAtlasiQ9HB55 baseline and differential
GenevisibleiQ9HB55 HS

Organism-specific databases

HPAiHPA066463
HPA072245

Interactioni

Protein-protein interaction databases

STRINGi9606.ENSP00000222382

Chemistry databases

BindingDBiQ9HB55

Structurei

3D structure databases

ProteinModelPortaliQ9HB55
SMRiQ9HB55
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the cytochrome P450 family.Curated

Phylogenomic databases

eggNOGiKOG0158 Eukaryota
COG2124 LUCA
GeneTreeiENSGT00900000140779
HOGENOMiHOG000039127
HOVERGENiHBG108567
InParanoidiQ9HB55
KOiK17692
OMAiTYSMGNV
OrthoDBiEOG091G0JNC
PhylomeDBiQ9HB55
TreeFamiTF105087

Family and domain databases

Gene3Di1.10.630.10, 1 hit
InterProiView protein in InterPro
IPR001128 Cyt_P450
IPR017972 Cyt_P450_CS
IPR008072 Cyt_P450_E_CYP3A
IPR002402 Cyt_P450_E_grp-II
IPR036396 Cyt_P450_sf
PfamiView protein in Pfam
PF00067 p450, 1 hit
PRINTSiPR00464 EP450II
PR01689 EP450IICYP3A
PR00385 P450
SUPFAMiSSF48264 SSF48264, 1 hit
PROSITEiView protein in PROSITE
PS00086 CYTOCHROME_P450, 1 hit

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q9HB55-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MDLIPNFAME TWVLVATSLV LLYIYGTHSH KLFKKLGIPG PTPLPFLGTI
60 70 80 90 100
LFYLRGLWNF DRECNEKYGE MWGLYEGQQP MLVIMDPDMI KTVLVKECYS
110 120 130 140 150
VFTNQMPLGP MGFLKSALSF AEDEEWKRIR TLLSPAFTSV KFKEMVPIIS
160 170 180 190 200
QCGDMLVRSL RQEAENSKSI NLKDFFGAYT MDVITGTLFG VNLDSLNNPQ
210 220 230 240 250
DPFLKNMKKL LKLDFLDPFL LLISLFPFLT PVFEALNIGL FPKDVTHFLK
260 270 280 290 300
NSIERMKESR LKDKQKHRVD FFQQMIDSQN SKETKSHKAL SDLELVAQSI
310 320 330 340 350
IIIFAAYDTT STTLPFIMYE LATHPDVQQK LQEEIDAVLP NKAPVTYDAL
360 370 380 390 400
VQMEYLDMVV NETLRLFPVV SRVTRVCKKD IEINGVFIPK GLAVMVPIYA
410 420 430 440 450
LHHDPKYWTE PEKFCPERFS KKNKDSIDLY RYIPFGAGPR NCIGMRFALT
460 470 480 490 500
NIKLAVIRAL QNFSFKPCKE TQIPLKLDNL PILQPEKPIV LKVHLRDGIT

SGP
Length:503
Mass (Da):57,670
Last modified:March 1, 2001 - v1
Checksum:i2C585B9DC573F634
GO
Isoform 2 (identifier: Q9HB55-2) [UniParc]FASTAAdd to basket

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

Show »
Length:504
Mass (Da):57,757
Checksum:iCB87C6873DAB7B0D
GO
Isoform 3 (identifier: Q9HB55-3) [UniParc]FASTAAdd to basket

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

Show »
Length:420
Mass (Da):48,304
Checksum:i60873437189BA207
GO
Isoform 4 (identifier: Q9HB55-4) [UniParc]FASTAAdd to basket

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.
Show »
Length:250
Mass (Da):28,490
Checksum:i858527154F617A06
GO
Isoform 7 (identifier: Q9HB55-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     56-224: GLWNFDRECN...FLDPFLLLIS → RSLNKIPSWA...VMKNTEKCGA

Show »
Length:393
Mass (Da):44,808
Checksum:iA0D1F6642FC1D9E1
GO

Polymorphismi

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.

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_01805025 – 88YGTHS…IMDPD → LGPIHINFLRSWEFLGQPLC LFWELFCSTLGVFGILTENV MKNTEKCGGCMRGNSPCWSS WIPT in allele CYP3A43*2. Add BLAST64
Natural variantiVAR_04844927T → A. Corresponds to variant dbSNP:rs45558032Ensembl.1
Natural variantiVAR_01805189 – 503Missing in allele CYP3A43*2. Add BLAST415
Natural variantiVAR_048450145M → I. Corresponds to variant dbSNP:rs45450092Ensembl.1
Natural variantiVAR_048451275M → I. Corresponds to variant dbSNP:rs45621431Ensembl.1
Natural variantiVAR_018052340P → A in allele CYP3A43*3. 1 PublicationCorresponds to variant dbSNP:rs680055Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_05673656 – 224GLWNF…LLLIS → RSLNKIPSWAWWLTPVIPAL WEAEAGGSPKVRSSRPALPT WVFGILTENVMKNTEKCGA in isoform 7. 1 PublicationAdd BLAST169
Alternative sequenceiVSP_000612224 – 250SLFPF…THFLK → YRVSLCCLGRSAWCDLGSLK PPPPGFE in isoform 4. CuratedAdd BLAST27
Alternative sequenceiVSP_000613251 – 503Missing in isoform 4. CuratedAdd BLAST253
Alternative sequenceiVSP_000609417E → ES in isoform 2. Curated1
Alternative sequenceiVSP_000610419 – 420FS → SH in isoform 3. Curated2
Alternative sequenceiVSP_000611421 – 503Missing in isoform 3. CuratedAdd BLAST83

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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
AC011904 Genomic DNA Translation: AAS07394.1
AC011904 Genomic DNA Translation: AAS07395.1
CH471091 Genomic DNA Translation: EAW76632.1
CH471091 Genomic DNA Translation: EAW76634.1
BC100981 mRNA Translation: AAI00982.1
CCDSiCCDS5675.1 [Q9HB55-2]
CCDS5676.1 [Q9HB55-1]
CCDS5677.1 [Q9HB55-3]
CCDS64723.1 [Q9HB55-6]
PIRiJC7627
RefSeqiNP_001265850.1, NM_001278921.1 [Q9HB55-6]
NP_073731.1, NM_022820.4 [Q9HB55-2]
NP_476436.1, NM_057095.2 [Q9HB55-1]
NP_476437.1, NM_057096.3 [Q9HB55-3]
UniGeneiHs.306220

Genome annotation databases

EnsembliENST00000222382; ENSP00000222382; ENSG00000021461 [Q9HB55-2]
ENST00000312017; ENSP00000312110; ENSG00000021461 [Q9HB55-3]
ENST00000354829; ENSP00000346887; ENSG00000021461 [Q9HB55-1]
ENST00000417625; ENSP00000416581; ENSG00000021461 [Q9HB55-6]
ENST00000434806; ENSP00000411653; ENSG00000021461 [Q9HB55-4]
GeneIDi64816
KEGGihsa:64816
UCSCiuc003urx.3 human [Q9HB55-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiCP343_HUMAN
AccessioniPrimary (citable) accession number: Q9HB55
Secondary accession number(s): Q495Y1
, Q75MK2, Q75MK3, Q9HB52, Q9HB53, Q9HB54, Q9HB57
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: March 1, 2001
Last modified: June 20, 2018
This is version 156 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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