CTR1_CRYNH
ID CTR1_CRYNH Reviewed; 288 AA.
AC J9VX37;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2013, sequence version 2.
DT 25-MAY-2022, entry version 41.
DE RecName: Full=CUF1-dependent copper transporter 1 {ECO:0000303|PubMed:21819456};
DE Short=Copper transporter 1 {ECO:0000303|PubMed:21819456};
GN Name=CTR1 {ECO:0000303|PubMed:21819456}; ORFNames=CNAG_07701;
OS Cryptococcus neoformans var. grubii serotype A (strain H99 / ATCC 208821 /
OS CBS 10515 / FGSC 9487) (Filobasidiella neoformans var. grubii).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Tremellomycetes;
OC Tremellales; Cryptococcaceae; Cryptococcus;
OC Cryptococcus neoformans species complex.
OX NCBI_TaxID=235443;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=H99 / ATCC 208821 / CBS 10515 / FGSC 9487;
RX PubMed=24743168; DOI=10.1371/journal.pgen.1004261;
RA Janbon G., Ormerod K.L., Paulet D., Byrnes E.J. III, Yadav V.,
RA Chatterjee G., Mullapudi N., Hon C.-C., Billmyre R.B., Brunel F.,
RA Bahn Y.-S., Chen W., Chen Y., Chow E.W.L., Coppee J.-Y., Floyd-Averette A.,
RA Gaillardin C., Gerik K.J., Goldberg J., Gonzalez-Hilarion S., Gujja S.,
RA Hamlin J.L., Hsueh Y.-P., Ianiri G., Jones S., Kodira C.D., Kozubowski L.,
RA Lam W., Marra M., Mesner L.D., Mieczkowski P.A., Moyrand F., Nielsen K.,
RA Proux C., Rossignol T., Schein J.E., Sun S., Wollschlaeger C., Wood I.A.,
RA Zeng Q., Neuveglise C., Newlon C.S., Perfect J.R., Lodge J.K., Idnurm A.,
RA Stajich J.E., Kronstad J.W., Sanyal K., Heitman J., Fraser J.A.,
RA Cuomo C.A., Dietrich F.S.;
RT "Analysis of the genome and transcriptome of Cryptococcus neoformans var.
RT grubii reveals complex RNA expression and microevolution leading to
RT virulence attenuation.";
RL PLoS Genet. 10:E1004261-E1004261(2014).
RN [2]
RP FUNCTION, INDUCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21819456; DOI=10.1111/j.1365-2958.2011.07794.x;
RA Ding C., Yin J., Tovar E.M., Fitzpatrick D.A., Higgins D.G., Thiele D.J.;
RT "The copper regulon of the human fungal pathogen Cryptococcus neoformans
RT H99.";
RL Mol. Microbiol. 81:1560-1576(2011).
RN [3]
RP FUNCTION.
RX PubMed=23498952; DOI=10.1016/j.chom.2013.02.002;
RA Ding C., Festa R.A., Chen Y.L., Espart A., Palacios O., Espin J.,
RA Capdevila M., Atrian S., Heitman J., Thiele D.J.;
RT "Cryptococcus neoformans copper detoxification machinery is critical for
RT fungal virulence.";
RL Cell Host Microbe 13:265-276(2013).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=25417972; DOI=10.1038/ncomms6550;
RA Sun T.S., Ju X., Gao H.L., Wang T., Thiele D.J., Li J.Y., Wang Z.Y.,
RA Ding C.;
RT "Reciprocal functions of Cryptococcus neoformans copper homeostasis
RT machinery during pulmonary infection and meningoencephalitis.";
RL Nat. Commun. 5:5550-5550(2014).
RN [5]
RP INDUCTION.
RX PubMed=29608794; DOI=10.1111/mmi.13960;
RA Garcia-Santamarina S., Festa R.A., Smith A.D., Yu C.H., Probst C., Ding C.,
RA Homer C.M., Yin J., Noonan J.P., Madhani H., Perfect J.R., Thiele D.J.;
RT "Genome-wide analysis of the regulation of Cu metabolism in Cryptococcus
RT neoformans.";
RL Mol. Microbiol. 108:473-494(2018).
RN [6]
RP FUNCTION, AND INTERACTION WITH BIM1.
RX PubMed=31932719; DOI=10.1038/s41589-019-0437-9;
RA Garcia-Santamarina S., Probst C., Festa R.A., Ding C., Smith A.D.,
RA Conklin S.E., Brander S., Kinch L.N., Grishin N.V., Franz K.J.,
RA Riggs-Gelasco P., Lo Leggio L., Johansen K.S., Thiele D.J.;
RT "A lytic polysaccharide monooxygenase-like protein functions in fungal
RT copper import and meningitis.";
RL Nat. Chem. Biol. 16:337-344(2020).
CC -!- FUNCTION: High affinity copper transporter involved in Cu(+) import
CC into the cell upon copper-limitating conditions (PubMed:21819456,
CC PubMed:23498952, PubMed:31932719). Functions with BIM1 and probably
CC also FRE4 and FRE7, where FRE4 and FRE7 metalloreductases liberate the
CC Cu(2+) bound to the BIM1 copper-binding site for subsequent import of
CC Cu(+) into the cell by CTR1, via the reduction of BIM1-bound Cu(2+) to
CC Cu(+) to reduce binding affinity for BIM1 but increase affinity for
CC CTR1 (Probable). The BIM1-CTR1 pathway for copper uptake plays a key
CC role in colonization in the brain where copper amounts are low and thus
CC in cryptococcal meningitis (PubMed:25417972, PubMed:31932719).
CC {ECO:0000269|PubMed:21819456, ECO:0000269|PubMed:23498952,
CC ECO:0000269|PubMed:25417972, ECO:0000269|PubMed:31932719,
CC ECO:0000305|PubMed:31932719}.
CC -!- SUBUNIT: Interacts with the copper acquisition factor BIM1.
CC {ECO:0000269|PubMed:31932719}.
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000305|PubMed:21819456};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- INDUCTION: Expression is induced by copper deficiency and regulated by
CC the CUF1 copper-dependent transcription factor (PubMed:21819456,
CC PubMed:29608794). The CTR1 promoter harbors the Cu-responsive element
CC (CuRE), which is critical for CUF1 binding and activation under copper-
CC limiting conditions (PubMed:29608794). {ECO:0000269|PubMed:21819456,
CC ECO:0000269|PubMed:29608794}.
CC -!- DISRUPTION PHENOTYPE: Leads to a severe growth defect in copper
CC deficiency conditions, but does not significantly affect melanin
CC production, nor fungal virulence (PubMed:21819456, PubMed:25417972).
CC However, when both CTR1 and CTR4 are disrupted, the colonization in the
CC brain and subsequent virulence are significantly reduced
CC (PubMed:25417972). {ECO:0000269|PubMed:21819456,
CC ECO:0000269|PubMed:25417972}.
CC -!- SIMILARITY: Belongs to the copper transporter (Ctr) (TC 1.A.56) family.
CC SLC31A subfamily. {ECO:0000305}.
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DR EMBL; CP003826; AFR96280.2; -; Genomic_DNA.
DR RefSeq; XP_012050436.1; XM_012195046.1.
DR AlphaFoldDB; J9VX37; -.
DR EnsemblFungi; AFR96280; AFR96280; CNAG_07701.
DR GeneID; 23890524; -.
DR VEuPathDB; FungiDB:CNAG_07701; -.
DR HOGENOM; CLU_966496_0_0_1; -.
DR Proteomes; UP000010091; Chromosome 7.
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:0005375; F:copper ion transmembrane transporter activity; IEA:InterPro.
DR InterPro; IPR007274; Cop_transporter.
DR PANTHER; PTHR12483; PTHR12483; 1.
DR Pfam; PF04145; Ctr; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Glycoprotein; Membrane; Transmembrane; Transmembrane helix.
FT CHAIN 1..288
FT /note="CUF1-dependent copper transporter 1"
FT /id="PRO_0000449517"
FT TRANSMEM 42..62
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 251..271
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 106..125
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 154..180
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 154..177
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 18
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 288 AA; 31538 MW; F6645FB118262C1D CRC64;
MDMSGMDGMD HMSSTSSNMS MSMKMYFHGT IGGDLLWFAS WMPSSAGATV GVCIGLFILA
IFERYLVAFR RACDAAWRRG QVGYVRPCSN GPLVFSSGKS TSLPPPVLFN RRSSTKKEKD
VYNPLTPSDY ALESNQDGSV EPVTPYTPSI HALRESQEGS SAPSYAHSQQ GQAQAQGSGV
GCDPCAEGRV AEIERCKEKA VERGLVHSHL PKAVRRSLDP GREGRWSRPF RLAVDVPRGL
LQALQTLIHY LLMLVVMTFN IWWMISVVIG CGVGEMLFGR FGSSHVGH
