NAG4_CANAL
ID NAG4_CANAL Reviewed; 581 AA.
AC Q59RG0;
DT 10-OCT-2018, integrated into UniProtKB/Swiss-Prot.
DT 26-APR-2005, sequence version 1.
DT 25-MAY-2022, entry version 105.
DE RecName: Full=Major facilitator superfamily multidrug transporter NAG4 {ECO:0000303|PubMed:12076781};
DE AltName: Full=N-acetylglucosamine utilization protein 4 {ECO:0000303|PubMed:12076781};
DE AltName: Full=Transmembrane protein 2 {ECO:0000303|PubMed:12589826};
GN Name=NAG4 {ECO:0000303|PubMed:12076781};
GN Synonyms=GAN4, IFY1, TMP2 {ECO:0000303|PubMed:12589826};
GN OrderedLocusNames=CAALFM_C604620CA; ORFNames=Aorf19.2160;
OS Candida albicans (strain SC5314 / ATCC MYA-2876) (Yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Debaryomycetaceae; Candida/Lodderomyces clade; Candida.
OX NCBI_TaxID=237561;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=15123810; DOI=10.1073/pnas.0401648101;
RA Jones T., Federspiel N.A., Chibana H., Dungan J., Kalman S., Magee B.B.,
RA Newport G., Thorstenson Y.R., Agabian N., Magee P.T., Davis R.W.,
RA Scherer S.;
RT "The diploid genome sequence of Candida albicans.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:7329-7334(2004).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=17419877; DOI=10.1186/gb-2007-8-4-r52;
RA van het Hoog M., Rast T.J., Martchenko M., Grindle S., Dignard D.,
RA Hogues H., Cuomo C., Berriman M., Scherer S., Magee B.B., Whiteway M.,
RA Chibana H., Nantel A., Magee P.T.;
RT "Assembly of the Candida albicans genome into sixteen supercontigs aligned
RT on the eight chromosomes.";
RL Genome Biol. 8:RESEARCH52.1-RESEARCH52.12(2007).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND GENOME REANNOTATION.
RC STRAIN=SC5314 / ATCC MYA-2876;
RX PubMed=24025428; DOI=10.1186/gb-2013-14-9-r97;
RA Muzzey D., Schwartz K., Weissman J.S., Sherlock G.;
RT "Assembly of a phased diploid Candida albicans genome facilitates allele-
RT specific measurements and provides a simple model for repeat and indel
RT structure.";
RL Genome Biol. 14:RESEARCH97.1-RESEARCH97.14(2013).
RN [4]
RP IDENTIFICATION.
RX PubMed=11298769; DOI=10.1046/j.1432-1327.2001.02135.x;
RA Yamada-Okabe T., Sakamori Y., Mio T., Yamada-Okabe H.;
RT "Identification and characterization of the genes for N-acetylglucosamine
RT kinase and N-acetylglucosamine-phosphate deacetylase in the pathogenic
RT fungus Candida albicans.";
RL Eur. J. Biochem. 268:2498-2505(2001).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12076781; DOI=10.1111/j.1574-6968.2002.tb11238.x;
RA Yamada-Okabe T., Yamada-Okabe H.;
RT "Characterization of the CaNAG3, CaNAG4, and CaNAG6 genes of the pathogenic
RT fungus Candida albicans: possible involvement of these genes in the
RT susceptibilities of cytotoxic agents.";
RL FEMS Microbiol. Lett. 212:15-21(2002).
RN [6]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=12589826; DOI=10.1016/s0006-291x(03)00094-9;
RA Sengupta M., Datta A.;
RT "Two membrane proteins located in the Nag regulon of Candida albicans
RT confer multidrug resistance.";
RL Biochem. Biophys. Res. Commun. 301:1099-1108(2003).
RN [7]
RP FUNCTION.
RX PubMed=19648376; DOI=10.1128/aem.00053-09;
RA Wendland J., Schaub Y., Walther A.;
RT "N-acetylglucosamine utilization by Saccharomyces cerevisiae based on
RT expression of Candida albicans NAG genes.";
RL Appl. Environ. Microbiol. 75:5840-5845(2009).
RN [8]
RP INDUCTION.
RX PubMed=25784162; DOI=10.1111/mmi.13002;
RA Fox E.P., Bui C.K., Nett J.E., Hartooni N., Mui M.C., Andes D.R.,
RA Nobile C.J., Johnson A.D.;
RT "An expanded regulatory network temporally controls Candida albicans
RT biofilm formation.";
RL Mol. Microbiol. 96:1226-1239(2015).
CC -!- FUNCTION: MFS transporter involved in N-acetylglucosamine (GlcNAc)
CC uptake (PubMed:19648376). Confers resistance to cycloheximide, 4-
CC nitroquinoline-N-oxide, and 1,10-phenanthroline, and contributes to
CC virulence (PubMed:12076781, PubMed:12589826).
CC {ECO:0000269|PubMed:12076781, ECO:0000269|PubMed:12589826,
CC ECO:0000269|PubMed:19648376}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC protein {ECO:0000255}.
CC -!- INDUCTION: Expression is induced in presence of cycloheximide and 4-
CC nitroquinoline-N-oxide (PubMed:12589826). Expression is up-regulated
CC during biofilm formation (PubMed:25784162).
CC {ECO:0000269|PubMed:12589826, ECO:0000269|PubMed:25784162}.
CC -!- DISRUPTION PHENOTYPE: Leads to increased susceptibility to
CC cycloheximide, 4-nitroquinoline-N-oxide, and 1,10-phenanthroline, but
CC not to actinomycin D, fluconazole, ketoconazole and colchicine
CC (PubMed:12076781). Leads also to attenuated virulence in mice
CC (PubMed:12076781). {ECO:0000269|PubMed:12076781}.
CC -!- SIMILARITY: Belongs to the major facilitator superfamily. DHA1 family.
CC Polyamines/proton antiporter (TC 2.A.1.2.16) subfamily. {ECO:0000305}.
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DR EMBL; CP017628; AOW30378.1; -; Genomic_DNA.
DR RefSeq; XP_712435.1; XM_707342.2.
DR AlphaFoldDB; Q59RG0; -.
DR EnsemblFungi; KHC73587; KHC73587; W5Q_05026.
DR EnsemblFungi; KHC82129; KHC82129; I503_05005.
DR GeneID; 3645978; -.
DR KEGG; cal:CAALFM_C604620CA; -.
DR CGD; CAL0000197244; NAG4.
DR VEuPathDB; FungiDB:C6_04620C_A; -.
DR eggNOG; KOG0255; Eukaryota.
DR HOGENOM; CLU_008455_11_5_1; -.
DR InParanoid; Q59RG0; -.
DR OMA; TIYMAIC; -.
DR OrthoDB; 608951at2759; -.
DR PHI-base; PHI:511; -.
DR Proteomes; UP000000559; Chromosome 6.
DR GO; GO:0005887; C:integral component of plasma membrane; IBA:GO_Central.
DR GO; GO:0022857; F:transmembrane transporter activity; IBA:GO_Central.
DR GO; GO:0008645; P:hexose transmembrane transport; IMP:CGD.
DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central.
DR Gene3D; 1.20.1250.20; -; 1.
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 2: Evidence at transcript level;
KW Cell membrane; Glycoprotein; Membrane; Reference proteome; Transmembrane;
KW Transmembrane helix; Transport; Virulence.
FT CHAIN 1..581
FT /note="Major facilitator superfamily multidrug transporter
FT NAG4"
FT /id="PRO_0000445246"
FT TRANSMEM 132..152
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 169..189
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 199..219
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 230..250
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 261..281
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 290..310
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 365..385
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 403..423
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 447..467
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 471..491
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 510..530
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 544..564
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..43
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 11
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 125
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 581 AA; 64592 MW; F680DCB429ECF553 CRC64;
MSHATDSTLD NASVDSEKVR DFGDDLQNHP VQPTRSILSK IRSRDDDARS LVSNNKGVER
IISDLQEGAG QLGPLEQPYD IKKIETHPDP HTDYNEADPW KYPIDSESGL RLVEWVDGDK
HNPKNISKAK KWLYTLVLGA VCFVVALGSA IVTGDMERPA EYFGVSEEVI ILASVTVFVI
GFGVGPLVFA PMSEEVGRKP IYVVTLFIAV VFIVPCGAAK NIATLIVCRL IDGIAFSAPM
TLIGGSLADI WEGPERGTAM AIFSAAPFLG PVCGPIFGGL LCDHAPTWRW IYWTFLIVAG
VFYAIFIAIV PETHHGILLK KRAKKLRKET GDSRYRSFNE LQIRSFGEVA KTSLLRPFVL
LSELIVFLMT IYMAICYGLL YMFFFAYPVV YQQGKGWSAS LTGVMFIPIG VGVIIATIAA
PFFNKDYNRR AQVYRDRGEL PPPELRLIPM MIACWFVPVG LFAFAWSSYT WVSWAGPCFS
GLAAGFGFCC LYNPANNYIV DSYQHYAASA LAAKTFVRSI WGACVPLFTI QMYHRLGDQW
ATSLMAFISL ACCAIPYLFF FFGARVRTFS RYAYTPETNT K
