ID   COPA_ENTHA              Reviewed;         727 AA.
AC   P32113; I6TBM0; Q47841;
DT   01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT   09-JAN-2013, sequence version 2.
DT   02-SEP-2026, entry version 160.
DE   RecName: Full=Probable copper-importing P-type ATPase A;
DE            EC=7.2.2.8 {ECO:0000269|PubMed:11162579};
GN   Name=copA; OrderedLocusNames=EHR_09085;
OS   Enterococcus hirae (strain ATCC 9790 / DSM 20160 / JCM 8729 / LMG 6399 /
OS   NBRC 3181 / NCIMB 6459 / NCDO 1258 / NCTC 12367 / WDCM 00089 / R).
OC   Bacteria; Bacillati; Bacillota; Bacilli; Lactobacillales; Enterococcaceae;
OC   Enterococcus.
OX   NCBI_TaxID=768486;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION IN COPPER HOMEOSTASIS.
RC   STRAIN=ATCC 9790 / DSM 20160 / JCM 8729 / LMG 6399 / NBRC 3181 / NCIMB
RC   6459 / NCDO 1258 / NCTC 12367 / WDCM 00089 / R;
RX   PubMed=8048974; DOI=10.1016/s0021-9258(18)31455-8;
RA   Odermatt A., Suter H., Krapf R., Solioz M.;
RT   "Primary structure of two P-type ATPases involved in copper homeostasis in
RT   Enterococcus hirae.";
RL   J. Biol. Chem. 268:12775-12779(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 9790 / DSM 20160 / JCM 8729 / LMG 6399 / NBRC 3181 / NCIMB
RC   6459 / NCDO 1258 / NCTC 12367 / WDCM 00089 / R;
RX   PubMed=22933757; DOI=10.1128/jb.01075-12;
RA   Gaechter T., Wunderlin C., Schmidheini T., Solioz M.;
RT   "Genome sequence of Enterococcus hirae (Streptococcus faecalis) ATCC 9790,
RT   a model organism for the study of ion transport, bioenergetics, and copper
RT   homeostasis.";
RL   J. Bacteriol. 194:5126-5127(2012).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-9.
RC   STRAIN=ATCC 9790 / DSM 20160 / JCM 8729 / LMG 6399 / NBRC 3181 / NCIMB
RC   6459 / NCDO 1258 / NCTC 12367 / WDCM 00089 / R;
RX   PubMed=7876197; DOI=10.1074/jbc.270.9.4349;
RA   Odermatt A., Solioz M.;
RT   "Two trans-acting metalloregulatory proteins controlling expression of the
RT   copper-ATPases of Enterococcus hirae.";
RL   J. Biol. Chem. 270:4349-4354(1995).
RN   [4]
RP   INDUCTION BY COPPER AND SILVER.
RC   STRAIN=ATCC 9790 / DSM 20160 / JCM 8729 / LMG 6399 / NBRC 3181 / NCIMB
RC   6459 / NCDO 1258 / NCTC 12367 / WDCM 00089 / R;
RX   PubMed=8037745; DOI=10.1006/bbrc.1994.1891;
RA   Odermatt A., Krapf R., Solioz M.;
RT   "Induction of the putative copper ATPases, CopA and CopB, of Enterococcus
RT   hirae by Ag+ and Cu2+, and Ag+ extrusion by CopB.";
RL   Biochem. Biophys. Res. Commun. 202:44-48(1994).
RN   [5]
RP   INTERACTION WITH COPZ, AND MUTAGENESIS OF CYS-17 AND CYS-20.
RC   STRAIN=ATCC 9790 / DSM 20160 / JCM 8729 / LMG 6399 / NBRC 3181 / NCIMB
RC   6459 / NCDO 1258 / NCTC 12367 / WDCM 00089 / R;
RX   PubMed=11594769; DOI=10.1006/bbrc.2001.5757;
RA   Multhaup G., Strausak D., Bissig K.-D., Solioz M.;
RT   "Interaction of the CopZ copper chaperone with the CopA copper ATPase of
RT   Enterococcus hirae assessed by surface plasmon resonance.";
RL   Biochem. Biophys. Res. Commun. 288:172-177(2001).
RN   [6]
RP   FUNCTION AS A COPPER ATPASE, CATALYTIC ACTIVITY, ACYLPHOSPHATE FORMATION,
RP   BIOPHYSICOCHEMICAL PROPERTIES, AND ACTIVITY REGULATION.
RC   STRAIN=ATCC 9790 / DSM 20160 / JCM 8729 / LMG 6399 / NBRC 3181 / NCIMB
RC   6459 / NCDO 1258 / NCTC 12367 / WDCM 00089 / R;
RX   PubMed=11162579; DOI=10.1006/bbrc.2000.4176;
RA   Wunderli-Ye H., Solioz M.;
RT   "Purification and functional analysis of the copper ATPase CopA of
RT   Enterococcus hirae.";
RL   Biochem. Biophys. Res. Commun. 280:713-719(2001).
CC   -!- FUNCTION: Probably involved in copper import under copper limiting
CC       conditions. {ECO:0000269|PubMed:11162579, ECO:0000269|PubMed:8048974}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=Cu(+)(in) + ATP + H2O = Cu(+)(out) + ADP + phosphate + H(+);
CC         Xref=Rhea:RHEA:25792, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:49552,
CC         ChEBI:CHEBI:456216; EC=7.2.2.8;
CC         Evidence={ECO:0000269|PubMed:11162579};
CC   -!- ACTIVITY REGULATION: Inhibited by vanadate.
CC       {ECO:0000269|PubMed:11162579}.
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=0.2 mM for ATP {ECO:0000269|PubMed:11162579};
CC         Vmax=0.15 umol/min/mg enzyme {ECO:0000269|PubMed:11162579};
CC       pH dependence:
CC         Optimum pH is 6.25. {ECO:0000269|PubMed:11162579};
CC   -!- SUBUNIT: Monomer. Interacts with the copper chaperone CopZ.
CC       {ECO:0000269|PubMed:11594769}.
CC   -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein.
CC   -!- INDUCTION: By copper and silver. {ECO:0000269|PubMed:8037745}.
CC   -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3)
CC       family. Type IB subfamily. {ECO:0000305}.
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DR   EMBL; L13292; AAA61835.1; -; Genomic_DNA.
DR   EMBL; CP003504; AFM70729.1; -; Genomic_DNA.
DR   EMBL; Z46807; CAA86837.1; -; Genomic_DNA.
DR   PIR; A45995; A45995.
DR   RefSeq; WP_010737925.1; NC_018081.1.
DR   AlphaFoldDB; P32113; -.
DR   SMR; P32113; -.
DR   TCDB; 3.A.3.5.1; the p-type atpase (p-atpase) superfamily.
DR   GeneID; 305470757; -.
DR   KEGG; ehr:EHR_09085; -.
DR   eggNOG; COG2217; Bacteria.
DR   HOGENOM; CLU_001771_0_3_9; -.
DR   OrthoDB; 9813266at2; -.
DR   SABIO-RK; P32113; -.
DR   Proteomes; UP000002895; Chromosome.
DR   GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR   GO; GO:0016887; F:ATP hydrolysis activity; IEA:InterPro.
DR   GO; GO:0005507; F:copper ion binding; IEA:TreeGrafter.
DR   GO; GO:0043682; F:P-type divalent copper transporter activity; IEA:TreeGrafter.
DR   GO; GO:0140581; F:P-type monovalent copper transporter activity; IEA:UniProtKB-EC.
DR   GO; GO:0055070; P:copper ion homeostasis; IEA:TreeGrafter.
DR   CDD; cd00371; HMA; 1.
DR   CDD; cd02094; P-type_ATPase_Cu-like; 1.
DR   FunFam; 3.30.70.100:FF:000005; Copper-exporting P-type ATPase A; 1.
DR   FunFam; 2.70.150.10:FF:000002; Copper-transporting ATPase 1, putative; 1.
DR   FunFam; 3.40.50.1000:FF:000020; Probable cation-transporting P-type ATPase; 1.
DR   Gene3D; 3.30.70.100; -; 1.
DR   Gene3D; 3.40.1110.10; Calcium-transporting ATPase, cytoplasmic domain N; 1.
DR   Gene3D; 2.70.150.10; Calcium-transporting ATPase, cytoplasmic transduction domain A; 1.
DR   Gene3D; 3.40.50.1000; HAD superfamily/HAD-like; 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; IPR059000; ATPase_P-type_domA.
DR   InterPro; IPR036412; HAD-like_sf.
DR   InterPro; IPR023214; HAD_sf.
DR   InterPro; IPR017969; Heavy-metal-associated_CS.
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   NCBIfam; TIGR01511; ATPase-IB1_Cu; 1.
DR   NCBIfam; TIGR01525; ATPase-IB_hvy; 1.
DR   NCBIfam; TIGR01494; ATPase_P-type; 1.
DR   PANTHER; PTHR43520; ATP7, ISOFORM B; 1.
DR   PANTHER; PTHR43520:SF8; P-TYPE CU(+) TRANSPORTER; 1.
DR   Pfam; PF00122; E1-E2_ATPase; 1.
DR   Pfam; PF00403; HMA; 1.
DR   Pfam; PF00702; Hydrolase; 1.
DR   PRINTS; PR00119; CATATPASE.
DR   PRINTS; PR00943; CUATPASE.
DR   PRINTS; PR00942; CUATPASEI.
DR   SFLD; SFLDG00002; C1.7:_P-type_atpase_like; 1.
DR   SFLD; SFLDS00003; Haloacid_Dehalogenase; 1.
DR   SFLD; SFLDF00027; p-type_atpase; 1.
DR   SUPFAM; SSF81653; Calcium ATPase, transduction domain A; 1.
DR   SUPFAM; SSF81665; Calcium ATPase, transmembrane domain M; 1.
DR   SUPFAM; SSF56784; HAD-like; 1.
DR   SUPFAM; SSF55008; HMA, heavy metal-associated domain; 1.
DR   PROSITE; PS00154; ATPASE_E1_E2; 1.
DR   PROSITE; PS01047; HMA_1; 1.
DR   PROSITE; PS50846; HMA_2; 1.
PE   1: Evidence at protein level;
KW   ATP-binding; Cell membrane; Copper; Copper transport; Ion transport;
KW   Magnesium; Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW   Reference proteome; Translocase; Transmembrane; Transmembrane helix;
KW   Transport.
FT   CHAIN           1..727
FT                   /note="Probable copper-importing P-type ATPase A"
FT                   /id="PRO_0000046250"
FT   TOPO_DOM        1..94
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        95..115
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        116..119
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        120..137
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        138..161
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        162..181
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        182..187
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        188..203
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        204..341
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        342..362
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        363..375
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        376..396
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        397..678
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        679..698
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        699..700
FT                   /note="Extracellular"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        701..721
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TOPO_DOM        722..727
FT                   /note="Cytoplasmic"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          6..70
FT                   /note="HMA"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT   ACT_SITE        425
FT                   /note="4-aspartylphosphate intermediate"
FT                   /evidence="ECO:0000250"
FT   BINDING         17
FT                   /ligand="Cu(+)"
FT                   /ligand_id="ChEBI:CHEBI:49552"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT   BINDING         20
FT                   /ligand="Cu(+)"
FT                   /ligand_id="ChEBI:CHEBI:49552"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00280"
FT   BINDING         621
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT   BINDING         625
FT                   /ligand="Mg(2+)"
FT                   /ligand_id="ChEBI:CHEBI:18420"
FT   MUTAGEN         17
FT                   /note="C->S: Still strongly interacts with CopZ but
FT                   abolishes the modulating activity of copper; when
FT                   associated with S-20."
FT                   /evidence="ECO:0000269|PubMed:11594769"
FT   MUTAGEN         20
FT                   /note="C->S: Still strongly interacts with CopZ but
FT                   abolishes the modulating activity of copper; when
FT                   associated with S-17."
FT                   /evidence="ECO:0000269|PubMed:11594769"
FT   CONFLICT        630
FT                   /note="A -> R (in Ref. 1; AAA61835)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   727 AA;  78303 MW;  30A0858F2389B22B CRC64;
     MATNTKMETF VITGMTCANC SARIEKELNE QPGVMSATVN LATEKASVKY TDTTTERLIK
     SVENIGYGAI LYDEAHKQKI AEEKQTYLRK MKFDLIFSAI LTLPLMLAMI AMMLGSHGPI
     VSFFHLSLVQ LLFALPVQFY VGWRFYKGAY HALKTKAPNM DVLVAIGTSA AFALSIYNGF
     FPSHSHDLYF ESSSMIITLI LLGKYLEHTA KSKTGDAIKQ MMSLQTKTAQ VLRDGKEETI
     AIDEVMIDDI LVIRPGEQVP TDGRIIAGTS ALDESMLTGE SVPVEKKEKD MVFGGTINTN
     GLIQIQVSQI GKDTVLAQII QMVEDAQGSK APIQQIADKI SGIFVPIVLF LALVTLLVTG
     WLTKDWQLAL LHSVSVLVIA CPCALGLATP TAIMVGTGVG AHNGILIKGG EALEGAAHLN
     SIILDKTGTI TQGRPEVTDV IGPKEIISLF YSLEHASEHP LGKAIVAYGA KVGAKTQPIT
     DFVAHPGAGI SGTINGVHYF AGTRKRLAEM NLSFDEFQEQ ALELEQAGKT VMFLANEEQV
     LGMIAVADQI KEDAKQAIEQ LQQKGVDVFM VTGDNQRAAQ AIGKQVGIDS DHIFAEVLPE
     EKANYVEKLQ KAGKKVGMVG DGINDAPALA LADVGIAMGS GTDIAMETAD VTLMNSHLTS
     INQMISLSAA TLKKIKQNLF WAFIYNTIGI PFAAFGFLNP IIAGGAMAFS SISVLLNSLS
     LNRKTIK
//