Adria_00130 : CDS information

Location

Organism	Streptomyces peucetius
Strain	ATCC 29050 (=NBRC 100596)
Entry name	Doxorubicin
Contig	M73758
Start / Stop / Direction	7,562 / 8,554 / + [in whole cluster] 471 / 1,463 / + [in contig]
Location	7562..8554 [in whole cluster] 471..1463 [in contig]
Type	CDS
Length	993 bp (330 aa)

Annotation

Category	4.3 transport
Product	multidrug resistance ABC transporter ATP-binding protein
Product (GenBank)	daunorubicin resistance protein
Gene
Gene (GenBank)	drrA
EC number
Keyword
Note
Note (GenBank)	protein has ATP binding site
Reference	ACC P32010 PmId [1924314] A bacterial analog of the mdr gene of mammalian tumor cells is present in Streptomyces peucetius, the producer of daunorubicin and doxorubicin. (Proc Natl Acad Sci U S A. , 1991) [9006006] Expression and characterization of DrrA and DrrB proteins of Streptomyces peucetius in Escherichia coli: DrrA is an ATP binding protein. (J Bacteriol. , 1997) [15709779] Biochemical characterization of domains in the membrane subunit DrrB that interact with the ABC subunit DrrA: identification of a conserved motif. (Biochemistry. , 2005) [19063901] Translational coupling controls expression and function of the DrrAB drug efflux pump. (J Mol Biol. , 2009) [20158521] Daunorubicin efflux in Streptomyces peucetius modulates biosynthesis by feedback regulation. (FEMS Microbiol Lett. , 2010) [24634217] The DrrAB efflux system of Streptomyces peucetius is a multidrug transporter of broad substrate specificity. (J Biol Chem. , 2014) [25721665] Characterization of a novel domain 'GATE' in the ABC protein DrrA and its role in drug efflux by the DrrAB complex. (Biochem Biophys Res Commun. , 2015) comment [PMID: 1924314](1991) DrrAは排出ABC transporterのATP結合タンパク質。Mg2+依存的にATP (or GTP) を結合。 doxorubicin or daunorubicinの添加で活性が上昇。 DrrBはABC-2 type transporterといわれているもの。 -- さらにいくつかの続報がでており、DrrABはATP依存的なdoxorubicinとdaunorubicinの排出ポンプとされている(PMID: 15709779など)。上記著者らでの最新の続報は、[PMID: 19063901] -- 違うグループでも報告あり。上記既報をrefとして採用している。 [PMID: 20158521](2010) drrAB(-)mutantはDNRに高い感受性あり。このmutantはwildと比べて、薬剤産生が10倍減。 key regulator dnrI and polyketide synthase gene dpsAの発現が激減。 regulatory genes dnrO and dnrNの発現は増。これらの結果から細胞内DNR濃度に基づくFeedback regulationを提唱。 -- [PMID: 24634217](2014) DrrAB systemはdoxorubicinとdaunorubicin以外の排出も可能なmultidrug transporterであることを実証。 doxorubicin輸送は複数の多剤耐性基質によって抑制され、競合阻害なものも非競合阻害なものもあることから、DrrAB systemにおいて2つ以上のdrug binding siteの可能性が示唆される。

Sequence

>multidrug resistance ABC transporter ATP-binding protein [daunorubicin resistance protein]
MNTQPTRAIETSGLVKVYNGTRAVDGLDLNVPAGLVYGILGPNGAGKSTTIRMLATLLRP
DGGTARVFGHDVTSEPDTVRRRISVTGQYASVDEGLTGTENLVMMGRLQGYSWARARERA
AELIDGFGLGDARDRLLKTYSGGMRRRLDIAASIVVTPDLLFLDEPTTGLDPRSRNQVWD
IVRALVDAGTTVLLTTQYLDEADQLADRIAVIDHGRVIAEGTTGELKSSLGSNVLRLRLH
DAQSRAEAERLLSAELGVTIHRDSDPTALSARIDDPRQGMRALAELSRTHLEVRSFSLGQ
SSLDEVFLALTGHPADDRSTEEAAEEEKVA

>multidrug resistance ABC transporter ATP-binding protein [daunorubicin resistance protein]
GTGAACACGCAGCCGACACGGGCCATCGAAACGTCCGGTCTCGTCAAGGTCTACAACGGG
ACGAGGGCGGTGGACGGCCTGGACCTCAACGTCCCGGCCGGTCTCGTCTACGGGATCCTG
GGGCCGAACGGCGCCGGCAAGTCCACCACCATCCGCATGCTGGCGACGCTGCTGCGTCCC
GACGGCGGTACGGCCCGGGTCTTCGGTCACGACGTGACGAGCGAACCCGATACGGTCCGC
CGCAGGATCAGTGTCACCGGCCAGTACGCCTCCGTCGACGAGGGCCTGACCGGTACGGAG
AACCTCGTCATGATGGGCCGGCTCCAGGGCTACTCCTGGGCCCGGGCCAGGGAGCGCGCC
GCCGAACTGATCGACGGCTTCGGACTGGGCGACGCCCGCGACCGGCTCCTGAAGACCTAC
TCCGGTGGCATGCGGCGGCGGCTCGACATCGCCGCGAGCATCGTCGTCACCCCCGACCTG
CTGTTCCTGGACGAACCGACCACCGGTCTCGACCCGCGCAGCCGGAACCAGGTCTGGGAC
ATCGTGCGGGCTCTGGTGGACGCCGGCACGACGGTGCTGCTGACGACGCAGTACCTCGAC
GAGGCGGACCAACTGGCCGACCGCATCGCGGTCATCGACCACGGCCGGGTGATCGCGGAG
GGCACCACCGGGGAGCTGAAGTCCTCGCTCGGGTCCAACGTCCTGCGGCTGCGCCTCCAC
GACGCCCAGTCGCGTGCCGAGGCGGAACGGCTGCTGAGCGCGGAACTGGGCGTCACGATC
CACCGCGACTCCGATCCGACGGCGCTGAGCGCGCGGATCGACGACCCCCGGCAGGGCATG
CGGGCCCTGGCCGAGCTGTCGCGCACGCACTTGGAGGTACGCAGTTTCTCCCTCGGCCAG
TCCAGTCTCGACGAGGTCTTCCTGGCGCTGACCGGCCACCCGGCCGATGACCGGTCCACG
GAAGAAGCGGCGGAAGAGGAGAAGGTGGCATGA

Feature

BLASTP Database:UniProtKB:2011_09	show BLAST table
InterPro Database:interpro:38.0	IPR003439 ABC transporter-like (Domain) PS50893 ABC_TRANSPORTER_2 PF00005 ABC_tran IPR003593 AAA+ ATPase domain (Domain) SM00382 AAA IPR005894 Daunorubicin resistance ABC transporter ATP-binding subunit (Family) TIGR01188 DrrA IPR017871 ABC transporter, conserved site (Conserved_site) PS00211 ABC_TRANSPORTER_1
SignalP	Eukaryota
TMHMM	No significant hit

Adria_00115 Adria_00140