VCX1_CRYNH
ID VCX1_CRYNH Reviewed; 606 AA.
AC J9VDQ4; T2BNY7;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 13-NOV-2013, sequence version 2.
DT 25-MAY-2022, entry version 45.
DE RecName: Full=Vacuolar calcium ion transporter {ECO:0000303|PubMed:20889719};
DE AltName: Full=Vacuolar calcium exchanger {ECO:0000303|PubMed:20889719};
GN Name=VCX1 {ECO:0000303|PubMed:20889719};
GN ORFNames=CNAG_00025 {ECO:0000312|EMBL:AFR92163.2};
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 {ECO:0000312|Proteomes:UP000010091};
RN [1] {ECO:0000312|Proteomes:UP000010091}
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] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
RX PubMed=20889719; DOI=10.1128/ec.00114-10;
RA Kmetzsch L., Staats C.C., Simon E., Fonseca F.L., de Oliveira D.L.,
RA Sobrino L., Rodrigues J., Leal A.L., Nimrichter L., Rodrigues M.L.,
RA Schrank A., Vainstein M.H.;
RT "The vacuolar Ca^2(+) exchanger Vcx1 is involved in calcineurin-dependent
RT Ca^2(+) tolerance and virulence in Cryptococcus neoformans.";
RL Eukaryot. Cell 9:1798-1805(2010).
RN [3] {ECO:0000305}
RP DISRUPTION PHENOTYPE.
RX PubMed=23895559; DOI=10.1111/febs.12458;
RA Kmetzsch L., Staats C.C., Cupertino J.B., Fonseca F.L., Rodrigues M.L.,
RA Schrank A., Vainstein M.H.;
RT "The calcium transporter Pmc1 provides Ca2+ tolerance and influences the
RT progression of murine cryptococcal infection.";
RL FEBS J. 280:4853-4864(2013).
RN [4] {ECO:0000305}
RP DISRUPTION PHENOTYPE.
RX PubMed=29113016; DOI=10.1111/cmi.12803;
RA Squizani E.D., Oliveira N.K., Reuwsaat J.C.V., Marques B.M., Lopes W.,
RA Gerber A.L., de Vasconcelos A.T.R., Lev S., Djordjevic J.T., Schrank A.,
RA Vainstein M.H., Staats C.C., Kmetzsch L.;
RT "Cryptococcal dissemination to the central nervous system requires the
RT vacuolar calcium transporter Pmc1.";
RL Cell. Microbiol. 20:0-0(2018).
CC -!- FUNCTION: Has a role in promoting intracellular calcium ion
CC sequestration via the exchange of calcium ions for hydrogen ions across
CC the vacuolar membrane. {ECO:0000269|PubMed:20889719}.
CC -!- SUBCELLULAR LOCATION: Vacuole membrane {ECO:0000269|PubMed:20889719};
CC Multi-pass membrane protein {ECO:0000255}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=J9VDQ4-1; Sequence=Displayed;
CC Name=2;
CC IsoId=J9VDQ4-2; Sequence=VSP_060770;
CC -!- DISRUPTION PHENOTYPE: Increases intracellular free calcium level
CC (PubMed:20889719). Decreases urease activity (PubMed:29113016).
CC Decreases concentration of the polysaccharide glucuronoxylomannan in
CC growth medium (PubMed:20889719). Decreases RNA level of ECA1
CC (PubMed:20889719). Increases RNA level of PMR1 and PMC1
CC (PubMed:20889719). Sensitive to cyclosporine A in combination with;
CC semi-permissive high temperature, or calcium chloride
CC (PubMed:20889719). Resistance to cyclosporine A in combination with
CC cadmium (PubMed:20889719). Normal cell wall integrity
CC (PubMed:20889719). Normal capsule size (PubMed:20889719). Decreases
CC virulence in a mouse intranasal inhalation infection model
CC (PubMed:20889719). Normal virulence in a mouse systemic infection model
CC (PubMed:29113016). Decreases susceptibility to phagocytosis by
CC macrophages (PubMed:20889719, PubMed:29113016). Enhances calcium
CC sensitivity of PMC1 disruption mutant (PubMed:23895559).
CC {ECO:0000269|PubMed:20889719, ECO:0000269|PubMed:23895559,
CC ECO:0000269|PubMed:29113016}.
CC -!- SIMILARITY: Belongs to the Ca(2+):cation antiporter (CaCA) (TC 2.A.19)
CC family. {ECO:0000255}.
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DR EMBL; CP003820; AFR92163.2; -; Genomic_DNA.
DR EMBL; CP003820; AGV15259.1; -; Genomic_DNA.
DR RefSeq; XP_012046156.1; XM_012190766.1. [J9VDQ4-1]
DR RefSeq; XP_012046471.1; XM_012191081.1. [J9VDQ4-2]
DR AlphaFoldDB; J9VDQ4; -.
DR SMR; J9VDQ4; -.
DR EnsemblFungi; AFR92163; AFR92163; CNAG_00025. [J9VDQ4-1]
DR EnsemblFungi; AGV15259; AGV15259; CNAG_00025. [J9VDQ4-2]
DR GeneID; 23883897; -.
DR VEuPathDB; FungiDB:CNAG_00025; -.
DR HOGENOM; CLU_008721_4_2_1; -.
DR PHI-base; PHI:3802; -.
DR Proteomes; UP000010091; Chromosome 1.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005774; C:vacuolar membrane; IDA:UniProtKB.
DR GO; GO:0015369; F:calcium:proton antiporter activity; IC:UniProtKB.
DR GO; GO:0140146; P:calcium ion import into vacuole; IMP:UniProtKB.
DR Gene3D; 1.20.1420.30; -; 2.
DR InterPro; IPR004713; CaH_exchang.
DR InterPro; IPR004837; NaCa_Exmemb.
DR InterPro; IPR044880; NCX_ion-bd_dom_sf.
DR PANTHER; PTHR31503; PTHR31503; 1.
DR Pfam; PF01699; Na_Ca_ex; 2.
PE 3: Inferred from homology;
KW Alternative splicing; Calcium; Calcium transport; Ion transport; Membrane;
KW Transmembrane; Transmembrane helix; Transport; Vacuole.
FT CHAIN 1..606
FT /note="Vacuolar calcium ion transporter"
FT /id="PRO_0000451209"
FT TOPO_DOM 1..137
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q99385"
FT TRANSMEM 138..158
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 159..170
FT /note="Vacuolar"
FT /evidence="ECO:0000250|UniProtKB:Q99385"
FT TRANSMEM 171..191
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 192..204
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q99385"
FT TRANSMEM 205..225
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 226..236
FT /note="Vacuolar"
FT /evidence="ECO:0000250|UniProtKB:Q99385"
FT TRANSMEM 237..257
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 258..272
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q99385"
FT TRANSMEM 273..293
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 294..313
FT /note="Vacuolar"
FT /evidence="ECO:0000250|UniProtKB:Q99385"
FT TRANSMEM 314..334
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 335..437
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q99385"
FT TRANSMEM 438..458
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 459..477
FT /note="Vacuolar"
FT /evidence="ECO:0000250|UniProtKB:Q99385"
FT TRANSMEM 478..498
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 499..505
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q99385"
FT TRANSMEM 506..526
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 527..535
FT /note="Vacuolar"
FT /evidence="ECO:0000250|UniProtKB:Q99385"
FT TRANSMEM 536..556
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 557..566
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:Q99385"
FT TRANSMEM 567..587
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 588..606
FT /note="Vacuolar"
FT /evidence="ECO:0000250|UniProtKB:Q99385"
FT REGION 1..110
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 376..434
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 30..83
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 93..108
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..12
FT /note="MSPPRRVSFPPD -> MFPQN (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_060770"
SQ SEQUENCE 606 AA; 64911 MW; B83782B518105F0A CRC64;
MSPPRRVSFP PDTLQEDPPL ADSPLSSPKL PEYDRQSSST PIVSSNLPTD TTNSASAGPR
RRQQPSRQVT LDASPPSATR RETTESARTQ RSRAGSRRTS NSLDPNPGLM RRVTTVLFTP
PKKIGKAPTY WGSMKAAITS TWLNVLLVFI PIGWALYLAK HNGGKDSISD TAVFCCTFIA
IIPLAGLLGF ATEEAALRLG QTLGGLLNAT LGNAVELIVA ILALIKCELQ VVQSSLVGSI
LSNILLVLGM CFFAGGVRFA EQAIKSTAAQ LNASLLLIAV IAVLIPSAFH FSISSSTSNT
DASELANGEG ADLLSMSHAV SILLLILYLG YLLFQMWTHA TYYVDDAVTG STQYPEAITN
VSEKLKFRNF HRRKHDEEES YSTATTVSDA AVPPSARAEG GEVPATHGPG TAAAETGNRV
EHEDAEEEEE EETPQMNVVC TIALMVIDTV LVGVTAEFLV DSINGMVESN PSLSAEWVGL
ILLPIVGNAA EHFTAVSVSV KDKLDLSISV AVGSSIQIAL FVIPVIELLA WTIGKPMTLL
FDPYESIVLF LSVLIVNQTL ADGRSNWMEG MVLMMLYIII AVSFWYYPGS TTATLLGCQD
SSSVTG
