NOTK_ASPSM
ID NOTK_ASPSM Reviewed; 563 AA.
AC E1ACQ6;
DT 11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT 02-NOV-2010, sequence version 1.
DT 25-MAY-2022, entry version 30.
DE RecName: Full=Efflux pump notK {ECO:0000303|PubMed:20722388};
DE AltName: Full=Notoamide biosynthesis cluster protein K {ECO:0000303|PubMed:20722388};
GN Name=notK {ECO:0000303|PubMed:20722388};
OS Aspergillus sp. (strain MF297-2).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX NCBI_TaxID=877550;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=MF297-2;
RX PubMed=20722388; DOI=10.1021/ja1049302;
RA Ding Y., de Wet J.R., Cavalcoli J., Li S., Greshock T.J., Miller K.A.,
RA Finefield J.M., Sunderhaus J.D., McAfoos T.J., Tsukamoto S., Williams R.M.,
RA Sherman D.H.;
RT "Genome-based characterization of two prenylation steps in the assembly of
RT the stephacidin and notoamide anticancer agents in a marine-derived
RT Aspergillus sp.";
RL J. Am. Chem. Soc. 132:12733-12740(2010).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=17304611; DOI=10.1002/anie.200604381;
RA Kato H., Yoshida T., Tokue T., Nojiri Y., Hirota H., Ohta T.,
RA Williams R.M., Tsukamoto S.;
RT "Notoamides A-D: prenylated indole alkaloids isolated from a marine-derived
RT fungus, Aspergillus sp.";
RL Angew. Chem. Int. Ed. 46:2254-2256(2007).
RN [3]
RP FUNCTION.
RX PubMed=23213353; DOI=10.1039/c2md20029e;
RA Li S., Anand K., Tran H., Yu F., Finefield J.M., Sunderhaus J.D.,
RA McAfoos T.J., Tsukamoto S., Williams R.M., Sherman D.H.;
RT "Comparative analysis of the biosynthetic systems for fungal
RT bicyclo[2.2.2]diazaoctane indole alkaloids: the (+)/(-)-notoamide,
RT paraherquamide and malbrancheamide pathways.";
RL Med. Chem. Commun. 3:987-996(2012).
CC -!- FUNCTION: Efflux pump; part of the gene cluster that mediates the
CC biosynthesis of notoamide, a fungal indole alkaloid that belongs to a
CC family of natural products containing a characteristic
CC bicyclo[2.2.2]diazaoctane core. {ECO:0000305|PubMed:20722388,
CC ECO:0000305|PubMed:23213353}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- BIOTECHNOLOGY: Notoamides have been shown to exhibit antitumoral
CC activities (PubMed:17304611). Notoamides A-C show moderate cytotoxicity
CC against HeLa and L1210 cells with IC(50) values in the range of 22-52
CC mg/ml, but the IC(50) value of notoamide D is greater than 100 mg/ml
CC (PubMed:17304611). Moreover, notoamide C induces G2/M-cell cycle arrest
CC at a concentration of 6.3 mg/ml (PubMed:17304611).
CC {ECO:0000269|PubMed:17304611}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily. TCR/Tet
CC family. {ECO:0000305}.
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DR EMBL; HM622670; ADM34144.1; -; Genomic_DNA.
DR AlphaFoldDB; E1ACQ6; -.
DR SMR; E1ACQ6; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0022857; F:transmembrane transporter activity; IEA:InterPro.
DR Gene3D; 1.20.1250.20; -; 2.
DR InterPro; IPR011701; MFS.
DR InterPro; IPR020846; MFS_dom.
DR InterPro; IPR036259; MFS_trans_sf.
DR Pfam; PF07690; MFS_1; 1.
DR SUPFAM; SSF103473; SSF103473; 1.
DR PROSITE; PS50850; MFS; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Membrane; Transmembrane; Transmembrane helix; Transport.
FT CHAIN 1..563
FT /note="Efflux pump notK"
FT /id="PRO_0000448816"
FT TRANSMEM 48..68
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 78..98
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 108..128
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 138..158
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 165..185
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 197..217
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 239..259
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 270..290
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 312..332
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 345..365
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 374..394
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 406..426
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 438..458
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 509..529
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..32
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 538..563
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 7..22
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 543..563
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 563 AA; 60297 MW; 7EFF06BD22891DD6 CRC64;
MTKDEDSGTT DGGYSTPDIA VQEKQDQPPA PEPEYATGFR LAAIMSTIFL STLLAALDIG
IVATAIPGIT DDFHRLDDVG WYGGACFLLV GSSAPMWGKL YKYFSAQLVY LVSVVIFLVG
SIVAAAAPNS AALIVGRALQ GWGCSGTLGG SVLMISYVAE PQKRAMLIGM WMSVFMFSTI
IGPLLGGAFT SEVTWRWCFW INLPVGGPVI ALVVLFFEVP KHIKPAPATW VEILRQLDLP
GFALLLTSLV CLTVALQWGG QTKSWSYGSV IATLVMWVVL TIAFFVVEWI QGDYAMVPLA
LLKPRLVWTN ALYGWIANLA NFQVLFYLPI YFQSIHGQSA IASGVNSLPF MAFFAAGSML
SGFLIGKTRL LQPYEFASGV LATVGAALLY TLDIDSSKAR YIGPQVIFGI GIGLGNQVPM
TALESFSKPE HIAPTTGVML MCNSISGAYF VTAAQSIFAN YMLKELASIA PDMDPIQVLT
TGASEVSHVF QGAELEAVLA AYLAGIKDVF AFSLAGAAFT VVLSLAIPFK KLPNMFAGPS
NGQEEEEGKK DGPAEKKEDE VAV
