ATU1_YEAST
ID ATU1_YEAST Reviewed; 1216 AA.
AC P38360; D6VQT9;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 197.
DE RecName: Full=P-type cation-transporting ATPase {ECO:0000303|PubMed:7754711};
DE EC=7.2.2.21 {ECO:0000269|PubMed:10743563, ECO:0000269|PubMed:17107946};
DE AltName: Full=Cadmium resistance protein 2 {ECO:0000303|PubMed:2249249};
DE AltName: Full=Cadmium-translocating P-type ATPase {ECO:0000303|PubMed:2249249};
DE AltName: Full=Cd(2+)-exporting ATPase {ECO:0000303|PubMed:2249249};
GN Name=PCA1 {ECO:0000303|PubMed:7754711};
GN Synonyms=CAD2 {ECO:0000303|PubMed:2249249}, PAY2;
GN OrderedLocusNames=YBR295W; ORFNames=YBR2112;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7754711; DOI=10.1002/yea.320100910;
RA Rad M.R., Kirchrath L., Hollenberg C.;
RT "A putative P-type Cu(2+)-transporting ATPase gene on chromosome II of
RT Saccharomyces cerevisiae.";
RL Yeast 10:1217-1225(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=7813418; DOI=10.1002/j.1460-2075.1994.tb06923.x;
RA Feldmann H., Aigle M., Aljinovic G., Andre B., Baclet M.C., Barthe C.,
RA Baur A., Becam A.-M., Biteau N., Boles E., Brandt T., Brendel M.,
RA Brueckner M., Bussereau F., Christiansen C., Contreras R., Crouzet M.,
RA Cziepluch C., Demolis N., Delaveau T., Doignon F., Domdey H.,
RA Duesterhus S., Dubois E., Dujon B., El Bakkoury M., Entian K.-D.,
RA Feuermann M., Fiers W., Fobo G.M., Fritz C., Gassenhuber J., Glansdorff N.,
RA Goffeau A., Grivell L.A., de Haan M., Hein C., Herbert C.J.,
RA Hollenberg C.P., Holmstroem K., Jacq C., Jacquet M., Jauniaux J.-C.,
RA Jonniaux J.-L., Kallesoee T., Kiesau P., Kirchrath L., Koetter P.,
RA Korol S., Liebl S., Logghe M., Lohan A.J.E., Louis E.J., Li Z.Y.,
RA Maat M.J., Mallet L., Mannhaupt G., Messenguy F., Miosga T., Molemans F.,
RA Mueller S., Nasr F., Obermaier B., Perea J., Pierard A., Piravandi E.,
RA Pohl F.M., Pohl T.M., Potier S., Proft M., Purnelle B., Ramezani Rad M.,
RA Rieger M., Rose M., Schaaff-Gerstenschlaeger I., Scherens B.,
RA Schwarzlose C., Skala J., Slonimski P.P., Smits P.H.M., Souciet J.-L.,
RA Steensma H.Y., Stucka R., Urrestarazu L.A., van der Aart Q.J.M.,
RA Van Dyck L., Vassarotti A., Vetter I., Vierendeels F., Vissers S.,
RA Wagner G., de Wergifosse P., Wolfe K.H., Zagulski M., Zimmermann F.K.,
RA Mewes H.-W., Kleine K.;
RT "Complete DNA sequence of yeast chromosome II.";
RL EMBO J. 13:5795-5809(1994).
RN [3]
RP GENOME REANNOTATION, AND SEQUENCE REVISION TO 382.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [4]
RP FUNCTION.
RX PubMed=2249249; DOI=10.1007/bf00318377;
RA Tohoyama H., Inouhe M., Joho M., Murayama T.;
RT "Resistance to cadmium is under control of the CAD2 gene in the yeast
RT Saccharomyces cerevisiae.";
RL Curr. Genet. 18:181-185(1990).
RN [5]
RP FUNCTION, AND MUTAGENESIS OF ARG-970.
RX PubMed=10743563; DOI=10.1007/s002940050013;
RA Shiraishi E., Inouhe M., Joho M., Tohoyama H.;
RT "The cadmium-resistant gene, CAD2, which is a mutated putative copper-
RT transporter gene (PCA1), controls the intracellular cadmium-level in the
RT yeast S. cerevisiae.";
RL Curr. Genet. 37:79-86(2000).
RN [6]
RP FUNCTION.
RX PubMed=14534306; DOI=10.1074/jbc.m212308200;
RA De Freitas J.M., Kim J.H., Poynton H., Su T., Wintz H., Fox T., Holman P.,
RA Loguinov A., Keles S., van der Laan M., Vulpe C.;
RT "Exploratory and confirmatory gene expression profiling of mac1Delta.";
RL J. Biol. Chem. 279:4450-4458(2004).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-970.
RX PubMed=17107946; DOI=10.1074/jbc.m609535200;
RA Adle D.J., Sinani D., Kim H., Lee J.;
RT "A cadmium-transporting P1B-type ATPase in yeast Saccharomyces
RT cerevisiae.";
RL J. Biol. Chem. 282:947-955(2007).
RN [8]
RP FUNCTION, MOTIF, UBIQUITINATION, AND MUTAGENESIS OF CYS-298; CYS-300;
RP CYS-311 AND CYS-312.
RX PubMed=18753133; DOI=10.1074/jbc.m806054200;
RA Adle D.J., Lee J.;
RT "Expressional control of a cadmium-transporting P1B-type ATPase by a metal
RT sensing degradation signal.";
RL J. Biol. Chem. 283:31460-31468(2008).
RN [9]
RP FUNCTION.
RX PubMed=21483812; DOI=10.1371/journal.pgen.1002034;
RA Chang S.L., Leu J.Y.;
RT "A tradeoff drives the evolution of reduced metal resistance in natural
RT populations of yeast.";
RL PLoS Genet. 7:E1002034-E1002034(2011).
CC -!- FUNCTION: Cadmium transporting P-type ATPase which plays a critical
CC role in cadmium resistance by extruding intracellular cadmium. Capable
CC of high affinity copper ion binding, but not active copper ion
CC transport. May play a role in copper resistance by chelating and
CC sequestering copper ions. {ECO:0000269|PubMed:10743563,
CC ECO:0000269|PubMed:14534306, ECO:0000269|PubMed:17107946,
CC ECO:0000269|PubMed:18753133, ECO:0000269|PubMed:21483812,
CC ECO:0000269|PubMed:2249249, ECO:0000269|PubMed:7754711}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + Cd(2+)(in) + H2O = ADP + Cd(2+)(out) + H(+) + phosphate;
CC Xref=Rhea:RHEA:12132, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:48775,
CC ChEBI:CHEBI:456216; EC=7.2.2.21;
CC Evidence={ECO:0000269|PubMed:10743563, ECO:0000269|PubMed:17107946};
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:17107946};
CC Multi-pass membrane protein {ECO:0000269|PubMed:17107946}.
CC -!- PTM: In the absence of cadmium, is ubiquitinated and targeted for
CC degradation before reaching the plasma membrane. This allows a rapid
CC and specific cellular response to cadmium.
CC {ECO:0000269|PubMed:18753133}.
CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3)
CC family. Type IB subfamily. {ECO:0000305}.
CC -!- CAUTION: Although initial characterizations described PCA1 as a copper-
CC transporting ATPase, subsequent experiments have demonstrated that PCA1
CC is capable of high affinity copper ion binding, but not active copper
CC ion transport. {ECO:0000305|PubMed:7754711}.
CC -!- CAUTION: Strain S288C, as well as other laboratory cadmium-sensitive
CC strains, contain a natural Gly-970-Arg mutation which eliminates
CC cadmium transport function. Loss of cadmium resistance provides a
CC fitness advantage under cadmium-free conditions. {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; Z29332; CAA82529.1; -; Genomic_DNA.
DR EMBL; Z36164; CAA85260.1; -; Genomic_DNA.
DR EMBL; BK006936; DAA07409.2; -; Genomic_DNA.
DR PIR; S46177; S46177.
DR RefSeq; NP_009854.2; NM_001178643.2.
DR AlphaFoldDB; P38360; -.
DR SMR; P38360; -.
DR BioGRID; 32988; 61.
DR DIP; DIP-6641N; -.
DR IntAct; P38360; 2.
DR STRING; 4932.YBR295W; -.
DR TCDB; 3.A.3.5.14; the p-type atpase (p-atpase) superfamily.
DR iPTMnet; P38360; -.
DR PaxDb; P38360; -.
DR PRIDE; P38360; -.
DR EnsemblFungi; YBR295W_mRNA; YBR295W; YBR295W.
DR GeneID; 852598; -.
DR KEGG; sce:YBR295W; -.
DR SGD; S000000499; PCA1.
DR VEuPathDB; FungiDB:YBR295W; -.
DR eggNOG; KOG0207; Eukaryota.
DR HOGENOM; CLU_001771_0_0_1; -.
DR InParanoid; P38360; -.
DR OMA; KEHVILS; -.
DR BioCyc; YEAST:G3O-29213-MON; -.
DR PRO; PR:P38360; -.
DR Proteomes; UP000002311; Chromosome II.
DR RNAct; P38360; protein.
DR GO; GO:0005887; C:integral component of plasma membrane; IDA:SGD.
DR GO; GO:0005886; C:plasma membrane; IDA:SGD.
DR GO; GO:0005839; C:proteasome core complex; IDA:SGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR GO; GO:0005507; F:copper ion binding; IMP:SGD.
DR GO; GO:0008551; F:P-type cadmium transporter activity; IMP:SGD.
DR GO; GO:0070628; F:proteasome binding; IPI:SGD.
DR GO; GO:0015691; P:cadmium ion transport; IMP:SGD.
DR GO; GO:0006875; P:cellular metal ion homeostasis; IMP:SGD.
DR GO; GO:0046686; P:response to cadmium ion; IEA:UniProtKB-KW.
DR GO; GO:0055085; P:transmembrane transport; IMP:SGD.
DR CDD; cd00371; HMA; 1.
DR Gene3D; 3.40.1110.10; -; 1.
DR Gene3D; 3.40.50.1000; -; 1.
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; IPR006121; HMA_dom.
DR InterPro; IPR036163; HMA_dom_sf.
DR InterPro; IPR027256; P-typ_ATPase_IB.
DR InterPro; IPR001757; P_typ_ATPase.
DR InterPro; IPR044492; P_typ_ATPase_HD_dom.
DR SFLD; SFLDF00027; p-type_atpase; 1.
DR SUPFAM; SSF55008; SSF55008; 1.
DR SUPFAM; SSF56784; SSF56784; 1.
DR SUPFAM; SSF81653; SSF81653; 1.
DR SUPFAM; SSF81665; SSF81665; 1.
DR TIGRFAMs; TIGR01525; ATPase-IB_hvy; 1.
DR TIGRFAMs; TIGR01494; ATPase_P-type; 1.
DR PROSITE; PS00154; ATPASE_E1_E2; 1.
DR PROSITE; PS50846; HMA_2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cadmium; Cadmium resistance; Cell membrane; Copper;
KW Ion transport; Magnesium; Membrane; Metal-binding; Nucleotide-binding;
KW Reference proteome; Translocase; Transmembrane; Transmembrane helix;
KW Transport; Ubl conjugation.
FT CHAIN 1..1216
FT /note="P-type cation-transporting ATPase"
FT /id="PRO_0000046317"
FT TOPO_DOM 1..556
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 557..578
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 579..592
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 593..612
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 613..620
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 621..641
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 642..659
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 660..680
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 681..808
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 809..831
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 832..847
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 848..865
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 866..1161
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 1162..1181
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1182..1190
FT /note="Extracellular"
FT /evidence="ECO:0000255"
FT TRANSMEM 1191..1209
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 1210..1216
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 410..477
FT /note="HMA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT REGION 250..350
FT /note="Metal-responding degradation signal"
FT ACT_SITE 903
FT /note="4-aspartylphosphate intermediate"
FT /evidence="ECO:0000250"
FT BINDING 421
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 424
FT /ligand="Cu cation"
FT /ligand_id="ChEBI:CHEBI:23378"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT BINDING 1107
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT BINDING 1111
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT MUTAGEN 298
FT /note="C->A: Abolishes copper resistance but not cadmium
FT resistance; when associated with A-300."
FT /evidence="ECO:0000269|PubMed:18753133"
FT MUTAGEN 300
FT /note="C->A: Abolishes copper resistance but not cadmium
FT resistance; when associated with A-298."
FT /evidence="ECO:0000269|PubMed:18753133"
FT MUTAGEN 311
FT /note="C->A: Abolishes cadmium resistance yet retains the
FT ability to confer copper resistance; when associated with
FT A-312."
FT /evidence="ECO:0000269|PubMed:18753133"
FT MUTAGEN 312
FT /note="C->A: Abolishes cadmium resistance yet retains the
FT ability to confer copper resistance; when associated with
FT A-311."
FT /evidence="ECO:0000269|PubMed:18753133"
FT MUTAGEN 970
FT /note="R->G: Confers localization to the plasma membrane
FT and cadmium transport function."
FT /evidence="ECO:0000269|PubMed:10743563,
FT ECO:0000269|PubMed:17107946"
FT CONFLICT 382
FT /note="H -> T (in Ref. 1; CAA82529 and 2; CAA85260)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 1216 AA; 131875 MW; E4DCAFB23AA1F138 CRC64;
MKPEKLFSGL GTSDGEYGVV NSENISIDAM QDNRGECHRR SIEMHANDNL GLVSQRDCTN
RPKITPQECL SETEQICHHG ENRTKAGLDV DDAETGGDHT NESRVDECCA EKVNDTETGL
DVDSCCGDAQ TGGDHTNESC VDGCCVRDSS VMVEEVTGSC EAVSSKEQLL TSFEVVPSKS
EGLQSIHDIR ETTRCNTNSN QHTGKGRLCI ESSDSTLKKR SCKVSRQKIE VSSKPECCNI
SCVERIASRS CEKRTFKGST NVGISGSSST DSLSEKFFSE QYSRMYNRYS SILKNLGCIC
NYLRTLGKES CCLPKVRFCS GEGASKKTKY SYRNSSGCLT KKKTHGDKER LSNDNGHADF
VCSKSCCTKM KDCAVTSTIS GHSSSEISRI VSMEPIENHL NLEAGSTGTE HIVLSVSGMS
CTGCESKLKK SFGALKCVHG LKTSLILSQA EFNLDLAQGS VKDVIKHLSK TTEFKYEQIS
NHGSTIDVVV PYAAKDFINE EWPQGVTELK IVERNIIRIY FDPKVIGARD LVNEGWSVPV
SIAPFSCHPT IEVGRKHLVR VGCTTALSII LTIPILVMAW APQLREKIST ISASMVLATI
IQFVIAGPFY LNALKSLIFS RLIEMDLLIV LSTSAAYIFS IVSFGYFVVG RPLSTEQFFE
TSSLLVTLIM VGRFVSELAR HRAVKSISVR SLQASSAILV DKTGKETEIN IRLLQYGDIF
KVLPDSRIPT DGTVISGSSE VDEALITGES MPVPKKCQSI VVAGSVNGTG TLFVKLSKLP
GNNTISTIAT MVDEAKLTKP KIQNIADKIA SYFVPTIIGI TVVTFCVWIA VGIRVEKQSR
SDAVIQAIIY AITVLIVSCP CVIGLAVPIV FVIASGVAAK RGVIFKSAES IEVAHNTSHV
VFDKTGTLTE GKLTVVHETV RGDRHNSQSL LLGLTEGIKH PVSMAIASYL KEKGVSAQNV
SNTKAVTGKR VEGTSYSGLK LQGGNCRWLG HNNDPDVRKA LEQGYSVFCF SVNGSVTAVY
ALEDSLRADA VSTINLLRQR GISLHILSGD DDGAVRSMAA RLGIESSNIR SHATPAEKSE
YIKDIVEGRN CDSSSQSKRP VVVFCGDGTN DAIGLTQATI GVHINEGSEV AKLAADVVML
KPKLNNILTM ITVSQKAMFR VKLNFLWSFT YNLFAILLAA GAFVDFHIPP EYAGLGELVS
ILPVIFVAIL LRYAKI
