ID   FTR1_RHIO9              Reviewed;         368 AA.
AC   I1BRD6; Q6VB93;
DT   20-JUN-2018, integrated into UniProtKB/Swiss-Prot.
DT   13-JUN-2012, sequence version 1.
DT   25-MAY-2022, entry version 40.
DE   RecName: Full=High affinity iron permease 1 {ECO:0000303|PubMed:15158278};
GN   Name=ftr1 {ECO:0000303|PubMed:15158278}; ORFNames=RO3G_03471;
OS   Rhizopus delemar (strain RA 99-880 / ATCC MYA-4621 / FGSC 9543 / NRRL
OS   43880) (Mucormycosis agent) (Rhizopus arrhizus var. delemar).
OC   Eukaryota; Fungi; Fungi incertae sedis; Mucoromycota; Mucoromycotina;
OC   Mucoromycetes; Mucorales; Mucorineae; Rhizopodaceae; Rhizopus.
OX   NCBI_TaxID=246409;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND INDUCTION.
RX   PubMed=15158278; DOI=10.1111/j.1574-6968.2004.tb09583.x;
RA   Fu Y., Lee H., Collins M., Tsai H.F., Spellberg B., Edwards J.E. Jr.,
RA   Kwon-Chung K.J., Ibrahim A.S.;
RT   "Cloning and functional characterization of the Rhizopus oryzae high
RT   affinity iron permease (rFTR1) gene.";
RL   FEMS Microbiol. Lett. 235:169-176(2004).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=RA 99-880 / ATCC MYA-4621 / FGSC 9543 / NRRL 43880;
RX   PubMed=19578406; DOI=10.1371/journal.pgen.1000549;
RA   Ma L.-J., Ibrahim A.S., Skory C., Grabherr M.G., Burger G., Butler M.,
RA   Elias M., Idnurm A., Lang B.F., Sone T., Abe A., Calvo S.E.,
RA   Corrochano L.M., Engels R., Fu J., Hansberg W., Kim J.-M., Kodira C.D.,
RA   Koehrsen M.J., Liu B., Miranda-Saavedra D., O'Leary S.,
RA   Ortiz-Castellanos L., Poulter R., Rodriguez-Romero J., Ruiz-Herrera J.,
RA   Shen Y.-Q., Zeng Q., Galagan J., Birren B.W., Cuomo C.A., Wickes B.L.;
RT   "Genomic analysis of the basal lineage fungus Rhizopus oryzae reveals a
RT   whole-genome duplication.";
RL   PLoS Genet. 5:E1000549-E1000549(2009).
RN   [3]
RP   FUNCTION, INDUCTION, DISRUPTION PHENOTYPE, AND BIOTECHNOLOGY.
RX   PubMed=20545847; DOI=10.1111/j.1365-2958.2010.07234.x;
RA   Ibrahim A.S., Gebremariam T., Lin L., Luo G., Husseiny M.I., Skory C.D.,
RA   Fu Y., French S.W., Edwards J.E. Jr., Spellberg B.;
RT   "The high affinity iron permease is a key virulence factor required for
RT   Rhizopus oryzae pathogenesis.";
RL   Mol. Microbiol. 77:587-604(2010).
RN   [4]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=27159390; DOI=10.1172/jci82744;
RA   Gebremariam T., Lin L., Liu M., Kontoyiannis D.P., French S.,
RA   Edwards J.E. Jr., Filler S.G., Ibrahim A.S.;
RT   "Bicarbonate correction of ketoacidosis alters host-pathogen interactions
RT   and alleviates mucormycosis.";
RL   J. Clin. Invest. 126:2280-2294(2016).
RN   [5]
RP   INDUCTION.
RX   PubMed=28610916; DOI=10.1016/j.biocel.2017.06.005;
RA   Carroll C.S., Grieve C.L., Murugathasan I., Bennet A.J., Czekster C.M.,
RA   Liu H., Naismith J., Moore M.M.;
RT   "The rhizoferrin biosynthetic gene in the fungal pathogen Rhizopus delemar
RT   is a novel member of the NIS gene family.";
RL   Int. J. Biochem. Cell Biol. 89:136-146(2017).
CC   -!- FUNCTION: High affinity iron permease required for iron uptake in iron-
CC       depleted environments (PubMed:15158278, PubMed:20545847). Required for
CC       full virulence in mice (PubMed:20545847). {ECO:0000269|PubMed:15158278,
CC       ECO:0000269|PubMed:20545847}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305}; Multi-pass membrane
CC       protein {ECO:0000255}.
CC   -!- INDUCTION: Expressed in iron-depleted conditions and repressed in iron-
CC       replete media (PubMed:15158278, PubMed:28610916). Induced during
CC       infection in diabetic ketoacidosis (DKA) mice (PubMed:20545847).
CC       {ECO:0000269|PubMed:15158278, ECO:0000269|PubMed:20545847,
CC       ECO:0000269|PubMed:28610916}.
CC   -!- DISRUPTION PHENOTYPE: Compromises the ability to acquire iron in vitro
CC       and reduced virulence in diabetic ketoacidosis (DKA) mice
CC       (PubMed:20545847). RNAi-mediated knockdown decreases virulence in a
CC       mouse model of 3-hydroxybutyric acid (BHB)-induced acidosis
CC       (PubMed:27159390). {ECO:0000269|PubMed:20545847,
CC       ECO:0000269|PubMed:27159390}.
CC   -!- BIOTECHNOLOGY: Passive immunization with anti-ftr1 immune sera protects
CC       DKA mice from infection (PubMed:20545847). Thus, ftr1 is a virulence
CC       factor and anti-ftr1 passive immunotherapy deserves further evaluation
CC       as a strategy to improve outcomes of deadly mucormycosis
CC       (PubMed:20545847). {ECO:0000269|PubMed:20545847}.
CC   -!- SIMILARITY: Belongs to the oxidase-dependent Fe transporter (OFeT) (TC
CC       9.A.10.1) family. {ECO:0000305}.
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DR   EMBL; AY344587; AAQ24109.1; -; Genomic_DNA.
DR   EMBL; CH476733; EIE78766.1; -; Genomic_DNA.
DR   AlphaFoldDB; I1BRD6; -.
DR   STRING; 936053.I1BRD6; -.
DR   EnsemblFungi; EIE78766; EIE78766; RO3G_03471.
DR   VEuPathDB; FungiDB:RO3G_03471; -.
DR   eggNOG; ENOG502QQWE; Eukaryota.
DR   InParanoid; I1BRD6; -.
DR   OMA; ITMLKMD; -.
DR   OrthoDB; 1158680at2759; -.
DR   PHI-base; PHI:4844; -.
DR   Proteomes; UP000009138; Unassembled WGS sequence.
DR   GO; GO:0033573; C:high-affinity iron permease complex; IEA:InterPro.
DR   GO; GO:0005381; F:iron ion transmembrane transporter activity; IEA:InterPro.
DR   GO; GO:0055072; P:iron ion homeostasis; IEA:UniProtKB-KW.
DR   InterPro; IPR004923; FTR1/Fip1/EfeU.
DR   PANTHER; PTHR31632; PTHR31632; 1.
DR   Pfam; PF03239; FTR1; 1.
PE   1: Evidence at protein level;
KW   Cell membrane; Ion transport; Iron; Iron transport; Membrane;
KW   Reference proteome; Transmembrane; Transmembrane helix; Transport;
KW   Virulence.
FT   CHAIN           1..368
FT                   /note="High affinity iron permease 1"
FT                   /id="PRO_0000444440"
FT   TRANSMEM        8..28
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        50..70
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        86..106
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        142..162
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        173..193
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        204..224
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        287..307
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   REGION          346..368
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        349..368
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ   SEQUENCE   368 AA;  41125 MW;  6AC97D811D28E1BF CRC64;
     MSQDLFNVPI FFILFRETTE AAIIISVLLS FLKRMFNTES PVYKRLRNQV WIGGAAGLFI
     CLCIGAAFIA VYYTVLNDLW GNSEDIWEGV FSLVAVIMIT AMGLAMLKTE RMQEKWKVKL
     AKAMQKSNSE KSSFKEKLQK YAFFVLPFIT VLREGLEAVV FIGGVSLGIQ GKSIPIAAIM
     GIICGCLVGF LIYRGGSLIQ LRWFFVFSTV VLYLVAAGLM AKGVGYLEQN AWNQVIGGEA
     ADVISYRVST AVWHVSWGDP EANNDTSGGW QIFNAILGWN NTATYGSIIS YCLYWLFVCC
     YLVFSYFKEK RAAIRKAEAG EWDDGDEALE NAKQYIGNDG EFIVEDKESD EEANNHPKEK
     IESDAIKA