Adria_00140 : CDS information

Location

Organism	Streptomyces peucetius
Strain	ATCC 29050 (=NBRC 100596)
Entry name	Doxorubicin
Contig	M73758
Start / Stop / Direction	8,551 / 9,402 / + [in whole cluster] 1,460 / 2,311 / + [in contig]
Location	8551..9402 [in whole cluster] 1460..2311 [in contig]
Type	CDS
Length	852 bp (283 aa)

Annotation

Category	4.3 transport
Product	multidrug resistance ABC transporter permease protein
Product (GenBank)	daunorubicin resistance protein
Gene
Gene (GenBank)	drrB
EC number
Keyword
Note
Note (GenBank)	hydrophobic protein
Reference	ACC P32011 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) 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(DXR) or daunorubicin(DNR)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DXRとDNRの排出ポンプとされている(PMID: 15709779)。上記著者らでの最新の続報は[PMID: 19063901](2009) -- 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 permease protein [daunorubicin resistance protein]
MTTSPGTVESTTPVSGQLRTVLSAGERPARATAVSATLTHLWRAMMAFKHFPVQLIDIVL
MPLIFLLMFTYLFGGAFADSTEEYLQFYLPGVTVQAVVMMTVYTGTSLNTDIHKGVFDRF
RTLPFWQPATLAGSLLGDVLRYVVALATTVSLGLLLGFRADGGFLGVVGAMLVLIVFGFS
VSWIFAALGVVASEPERVSGTSMIVLYPLLFMSNIFVMPETMPGWMQAIVDANPMSHAAT
ASRELMHGTAGFWDVGLVLCVSAGLVAVFAPLTMRLYRNKNAH

>multidrug resistance ABC transporter permease protein [daunorubicin resistance protein]
ATGACGACGTCCCCCGGCACCGTGGAATCCACGACCCCTGTGAGCGGTCAGCTGCGGACG
GTGCTGTCCGCGGGTGAACGGCCGGCCCGCGCGACGGCGGTGTCCGCCACCCTGACCCAT
CTGTGGCGGGCGATGATGGCGTTCAAGCACTTCCCGGTGCAGCTGATCGACATCGTCCTG
ATGCCGTTGATCTTCCTGCTGATGTTCACGTACCTGTTCGGCGGGGCGTTCGCGGACTCC
ACCGAGGAGTACCTGCAGTTCTACCTCCCGGGCGTGACGGTGCAGGCGGTCGTCATGATG
ACGGTCTACACCGGCACCTCGCTCAACACGGACATCCACAAGGGCGTATTCGACCGTTTC
CGGACGCTCCCCTTCTGGCAGCCGGCGACGCTCGCGGGCAGTCTCCTCGGTGACGTGCTC
CGGTACGTCGTCGCCCTGGCGACCACGGTGTCCCTCGGGCTGCTGCTGGGCTTCCGCGCC
GACGGCGGTTTCCTCGGCGTGGTCGGCGCGATGCTGGTGCTGATCGTCTTCGGGTTCAGC
GTGAGCTGGATCTTCGCCGCCCTGGGCGTGGTGGCCAGCGAGCCCGAACGGGTCTCCGGG
ACCAGCATGATCGTGCTGTATCCGCTGCTGTTCATGAGCAACATCTTCGTCATGCCGGAG
ACGATGCCCGGCTGGATGCAGGCCATCGTCGACGCCAACCCGATGAGCCACGCGGCGACG
GCCTCCCGCGAGCTCATGCACGGCACGGCCGGCTTCTGGGACGTGGGCCTGGTCCTGTGC
GTGTCGGCAGGGCTGGTGGCCGTCTTCGCACCGCTGACCATGCGTCTGTACCGCAACAAG
AACGCCCACTGA

Feature

BLASTP Database:UniProtKB:2011_09	show BLAST table
InterPro Database:interpro:38.0	IPR000412 ABC-2 (Family) PS51012 ABC_TM2 IPR013525 ABC-2 type transporter (Domain) PF01061 ABC2_membrane
SignalP	Bacteria, Gram-positive
TMHMM	Transmembrane 5

Adria_00130 Adria_00150