ID   CTR4_CRYNH              Reviewed;         199 AA.
AC   J9VLN4;
DT   13-APR-2016, integrated into UniProtKB/Swiss-Prot.
DT   13-NOV-2013, sequence version 2.
DT   25-MAY-2022, entry version 34.
DE   RecName: Full=Copper transport protein CTR4 {ECO:0000305};
DE            Short=Copper transporter 4 {ECO:0000305};
GN   Name=CTR4 {ECO:0000303|PubMed:15334556}; ORFNames=CNAG_00979;
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   INDUCTION, AND BIOTECHNOLOGY.
RX   PubMed=15334556; DOI=10.1002/yea.1139;
RA   Ory J.J., Griffith C.L., Doering T.L.;
RT   "An efficiently regulated promoter system for Cryptococcus neoformans
RT   utilizing the CTR4 promoter.";
RL   Yeast 21:919-926(2004).
RN   [3]
RP   INDUCTION, AND FUNCTION.
RX   PubMed=17290306; DOI=10.1172/jci30006;
RA   Waterman S.R., Hacham M., Hu G., Zhu X., Park Y.D., Shin S., Panepinto J.,
RA   Valyi-Nagy T., Beam C., Husain S., Singh N., Williamson P.R.;
RT   "Role of a CUF1/CTR4 copper regulatory axis in the virulence of
RT   Cryptococcus neoformans.";
RL   J. Clin. Invest. 117:794-802(2007).
RN   [4]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=23033470; DOI=10.1128/mbio.00285-12;
RA   Waterman S.R., Park Y.D., Raja M., Qiu J., Hammoud D.A., O'Halloran T.V.,
RA   Williamson P.R.;
RT   "Role of CTR4 in the virulence of Cryptococcus neoformans.";
RL   MBio 3:0-0(2012).
CC   -!- FUNCTION: Required for high affinity copper (probably reduced Cu I)
CC       transport into the cell (By similarity). Plays a role in fungal
CC       pathogenesis during host infection (PubMed:17290306, PubMed:23033470).
CC       {ECO:0000250|UniProtKB:O94722, ECO:0000269|PubMed:17290306,
CC       ECO:0000269|PubMed:23033470}.
CC   -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Multi-pass membrane
CC       protein {ECO:0000255}.
CC   -!- INDUCTION: Expression is highly induced by the CUF1 copper regulatory
CC       factor in response to copper deprivation and repressed in presence of
CC       physiologically low concentrations of copper (PubMed:15334556,
CC       PubMed:17290306). Expressed at high levels after phagocytosis by
CC       macrophage-like cells and during infection of mouse brains, but not
CC       lungs, consistent with limited copper availability during neurologic
CC       infection (PubMed:17290306). {ECO:0000269|PubMed:15334556,
CC       ECO:0000269|PubMed:17290306}.
CC   -!- DISRUPTION PHENOTYPE: Exhibits a significant reduction in survival in
CC       macrophages after activation with gamma interferon (PubMed:23033470).
CC       {ECO:0000269|PubMed:23033470}.
CC   -!- BIOTECHNOLOGY: The CTR4 copper-sensing promoter can be used to
CC       construct plasmids that offer efficient and regulated expression in
CC       C.neoformans (PubMed:15334556). {ECO:0000269|PubMed:15334556}.
CC   -!- SIMILARITY: Belongs to the copper transporter (Ctr) (TC 1.A.56) family.
CC       SLC31A subfamily. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; CP003824; AFR95168.2; -; Genomic_DNA.
DR   RefSeq; XP_012049107.1; XM_012193717.1.
DR   AlphaFoldDB; J9VLN4; -.
DR   EnsemblFungi; AFR95168; AFR95168; CNAG_00979.
DR   GeneID; 23884725; -.
DR   VEuPathDB; FungiDB:CNAG_00979; -.
DR   Proteomes; UP000010091; Chromosome 5.
DR   GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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   Membrane; Transmembrane; Transmembrane helix.
FT   CHAIN           1..199
FT                   /note="Copper transport protein CTR4"
FT                   /id="PRO_0000436050"
FT   TRANSMEM        62..82
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        152..172
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
SQ   SEQUENCE   199 AA;  21810 MW;  1FEF4DB0B112F3E8 CRC64;
     MDMGNMGMGM GMGMDSGHNH SHMNMGSGHG ADSGHACRIS MLLNFNTVDA CFLSPNWHIR
     SKGMFAGSII GIFFLCVLIE LIRRLGREFD RWLVKRAGVN STCGELSSVA EYGKDGAQGG
     AVVRVAPRFR YVPSWPHQIL RGFIYGSQFT AAFFVMLLGM YFNVIVLIFI FLGQTVGYML
     FGRDTCGGGF DFGAQGRCC