ATC2_CRYNH
ID ATC2_CRYNH Reviewed; 1414 AA.
AC J9VQQ3;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2012, sequence version 1.
DT 03-AUG-2022, entry version 65.
DE RecName: Full=Calcium-transporting ATPase 2 {ECO:0000303|PubMed:23895559};
DE EC=7.2.2.10 {ECO:0000255|RuleBase:RU361146};
GN Name=PMC1 {ECO:0000303|PubMed:23895559};
GN ORFNames=CNAG_01232 {ECO:0000312|EMBL:AFR94914.1};
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, AND 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 [3] {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: This magnesium-dependent enzyme catalyzes the hydrolysis of
CC ATP coupled with the transport of calcium (By similarity). Transports
CC calcium to the vacuole and participates in the control of cytosolic
CC free calcium (PubMed:23895559). {ECO:0000250|UniProtKB:P38929,
CC ECO:0000269|PubMed:23895559}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + Ca(2+)(in) + H2O = ADP + Ca(2+)(out) + H(+) + phosphate;
CC Xref=Rhea:RHEA:18105, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:29108, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474,
CC ChEBI:CHEBI:456216; EC=7.2.2.10;
CC Evidence={ECO:0000255|RuleBase:RU361146};
CC -!- SUBCELLULAR LOCATION: Vacuole membrane {ECO:0000250|UniProtKB:P38929};
CC Multi-pass membrane protein {ECO:0000255|RuleBase:RU361146}.
CC -!- DISRUPTION PHENOTYPE: Increases cytosolic free calcium level
CC (PubMed:23895559). Resistance to cadmium (PubMed:23895559). Decreases
CC cell population growth in serum (PubMed:29113016). Sensitive to calcium
CC (PubMed:23895559). Abnormal level of calcineurin-mediated signaling
CC pathway gene RNA, transepithelial migration gene RNA, and antioxidant
CC gene RNA (PubMed:29113016). Decreases VCX1 RNA level and increases ECA1
CC RNA level during cellular response to calcium (PubMed:23895559).
CC Decreases urease activity (PubMed:29113016). Avirulence in a mouse
CC systemic model of infection; decreases lung fungal burden and abolishes
CC brain fungal burden (PubMed:29113016). Decreases virulence in a mouse
CC intranasal inhalation infection model; decreases lung fungal burden and
CC abolishes brain fungal burden (PubMed:23895559). Severely decreases
CC transepithelial migration through the host blood-brain barrier
CC (PubMed:29113016). Increases susceptibility to phagocytosis by
CC macrophages (PubMed:29113016). Phenotypes enhanced in a double knockout
CC with VCX1 (PubMed:23895559). {ECO:0000269|PubMed:23895559,
CC ECO:0000269|PubMed:29113016}.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3)
CC family. {ECO:0000255|RuleBase:RU361146}.
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DR EMBL; CP003824; AFR94914.1; -; Genomic_DNA.
DR RefSeq; XP_012049404.1; XM_012194014.1.
DR AlphaFoldDB; J9VQQ3; -.
DR SMR; J9VQQ3; -.
DR EnsemblFungi; AFR94914; AFR94914; CNAG_01232.
DR GeneID; 23884966; -.
DR VEuPathDB; FungiDB:CNAG_01232; -.
DR HOGENOM; CLU_002360_9_3_1; -.
DR PHI-base; PHI:3801; -.
DR Proteomes; UP000010091; Chromosome 5.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0005774; C:vacuolar membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0005388; F:P-type calcium transporter activity; IGI:UniProtKB.
DR GO; GO:0140146; P:calcium ion import into vacuole; IGI:UniProtKB.
DR Gene3D; 3.40.1110.10; -; 1.
DR Gene3D; 3.40.50.1000; -; 1.
DR InterPro; IPR006068; ATPase_P-typ_cation-transptr_C.
DR InterPro; IPR004014; ATPase_P-typ_cation-transptr_N.
DR InterPro; IPR023299; ATPase_P-typ_cyto_dom_N.
DR InterPro; IPR018303; ATPase_P-typ_P_site.
DR InterPro; IPR023298; ATPase_P-typ_TM_dom_sf.
DR InterPro; IPR008250; ATPase_P-typ_transduc_dom_A_sf.
DR InterPro; IPR036412; HAD-like_sf.
DR InterPro; IPR023214; HAD_sf.
DR InterPro; IPR006408; P-type_ATPase_IIB.
DR InterPro; IPR001757; P_typ_ATPase.
DR InterPro; IPR044492; P_typ_ATPase_HD_dom.
DR Pfam; PF00689; Cation_ATPase_C; 1.
DR Pfam; PF00690; Cation_ATPase_N; 1.
DR PRINTS; PR00120; HATPASE.
DR SFLD; SFLDF00027; p-type_atpase; 1.
DR SMART; SM00831; Cation_ATPase_N; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR SUPFAM; SSF81653; SSF81653; 1.
DR SUPFAM; SSF81660; SSF81660; 1.
DR SUPFAM; SSF81665; SSF81665; 1.
DR TIGRFAMs; TIGR01517; ATPase-IIB_Ca; 1.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 1.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
PE 3: Inferred from homology;
KW ATP-binding; Calcium; Calcium transport; Ion transport; Magnesium;
KW Membrane; Metal-binding; Nucleotide-binding; Translocase; Transmembrane;
KW Transmembrane helix; Transport; Vacuole.
FT CHAIN 1..1414
FT /note="Calcium-transporting ATPase 2"
FT /id="PRO_0000451210"
FT TOPO_DOM 1..327
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 328..348
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 349..370
FT /note="Vacuolar"
FT /evidence="ECO:0000305"
FT TRANSMEM 371..391
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 392..541
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 542..562
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 563..585
FT /note="Vacuolar"
FT /evidence="ECO:0000305"
FT TRANSMEM 586..606
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 607..1040
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1041..1061
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1062..1068
FT /note="Vacuolar"
FT /evidence="ECO:0000305"
FT TRANSMEM 1069..1089
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1090..1118
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1119..1139
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1140..1153
FT /note="Vacuolar"
FT /evidence="ECO:0000305"
FT TRANSMEM 1154..1171
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1172..1191
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 1192..1212
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1213..1223
FT /note="Vacuolar"
FT /evidence="ECO:0000305"
FT TRANSMEM 1224..1244
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1245..1414
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT REGION 1..231
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 265..294
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1376..1414
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 21..36
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 37..59
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 74..115
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 177..192
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 199..225
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1394..1414
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 642
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 595
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 600
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 642
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 644
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 644
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 737
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 779
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 909..911
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 958
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 964
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 983
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 986
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 1049
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 1079
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 1083
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 1083
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04191"
FT BINDING 1208
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P04191"
SQ SEQUENCE 1414 AA; 153384 MW; 9C2396F0FC8417DB CRC64;
MSRNNPPPVI ITTDPDSPAL HSAPSTPPPN QRPTPTLVIP GSPASESSHP ESPQGNDPFR
LSPNARLYPP GSGHSPTPSY SSALTPPSPT LTSSSSVHFS DELPTPSSPN PKTSLALRDN
HPDARSGMET LQTVDENDPQ RRHARGWSIG TWSSAAPTAD GYSMKKPLIR TATGASEVDG
DRGEDDANKK GKKDKKGKKG KKDKEEPPSA HLDPDKDKTD PTPFREKPSR LAMLVDPKSL
EDLEKIGGVS GLLEGLGVDG EKGLAVGTDE GNAENGAPRS SADMPGGNGP QWRASMDRRR
DIYGRNDLPR RKSKSLLLLM WLAFKDKVLI LLSVAAVVSL ALGLYQDLGT PPKIIYNDEC
PDGCEEAQVD WVEGVAIVVA IIIVVLVGSI NDWQKERQFK KLNEKREDRN VKVIRGGSEM
VINVKDVVVG DVCLLEPGEI IPVDGIFLRG HNVRCDESGA TGESDAIKKF SYDECIKERD
NLQPGQRQKK DCFLISGAKV LEGVGEYVVI AVGPTSFNGR IMMAMRGDAD ETPLQIKLNH
LAELIAKLGG ASGLLLFIAL MIRFFVQLKT NPDRSANDKA QSFIQILIIA VTLVVVAVPE
GLPLAVTLAL AFATKRMTKQ NLLVRVLGSC ETMANATVVC TDKTGTLTQN EMTVVAGSLG
VHGKFVKDLS DNASRSNANE GEGHSVHGDF SFDMSQLNDY ASSSLQTLFN EAICINSTAF
EDKNEEGKLN FVGSKTETAL LRFAKDMEWP NYRQVRESAE IVQMIPFSSE LKAMGVVVRK
DDTYRLYLKG ASEVLSNNCT RHVVVHQDGN KGDDIETTEF DDDTMSNISK TIIFYANQSL
RTIALCYRDF ESWPPAGTEK DGADEVPYEA IAKDMTLIAI TGIEDPLRPG VREAVEKCQL
AGVAVKMCTG DNVLTARSIA SQCGIFTAGG VVMEGPLFRK LSDSDRLEIA PRLQILARSS
PEDKRLLVKT LKSMGEVVGV TGDGTNDGPA LKLANVGFAM GIAGTEVAKE ASDIILMDDS
FKNIVLAIMW GRCVNDSVKK FLQFQISVNI TAVFITFISA VASSSEESVL TAVQLLWVNL
IMDTFAALAL ATDPATESSL DRKPDRKNAP LITVEMFKMI MVQAIYQIIV CLVLHFAGLK
ILGLEDNDQN NTELGALVFN CFVFCQIFNQ LNCRRLDRKL NVLEGFWRNW YFIIIFLIMV
GGQILIVEVG GAAFQVTRLG GRDWGITLVI GALSLPIGAL VRLTPTGPFA RLLVKLHIYA
DPNKLPELSP EAEEEQYSYN PALSRVKDNL STYARIRGGR LRASSMVAKS RNAQLRDADI
QFPSLLTMVP TVIAGTVGAG AHWVTPHNSI GLSNPAGQDP SYSTAELFKG KVQLHPRTNP
DDPLYAKFGL QPPESRGSSV SGAEGLSSGD ANNV
