ID ZNTA_ECOLI Reviewed; 732 AA. AC P37617; Q2M7D2; DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1994, sequence version 1. DT 27-MAR-2024, entry version 204. DE RecName: Full=Zinc/cadmium/lead-transporting P-type ATPase {ECO:0000305}; DE EC=7.2.2.- {ECO:0000269|PubMed:10660539, ECO:0000269|PubMed:17326661}; DE EC=7.2.2.12 {ECO:0000269|PubMed:10660539, ECO:0000269|PubMed:17326661, ECO:0000269|PubMed:9405611}; DE EC=7.2.2.21 {ECO:0000269|PubMed:10660539, ECO:0000269|PubMed:17326661, ECO:0000269|PubMed:9405611}; DE AltName: Full=Pb(II)/Cd(II)/Zn(II)-translocating ATPase {ECO:0000303|PubMed:10660539}; DE AltName: Full=Zn(2+)/Cd(2+)/Pb(2+) export ATPase {ECO:0000305}; GN Name=zntA {ECO:0000303|PubMed:9364914, ECO:0000303|PubMed:9405611}; GN Synonyms=yhhO; OrderedLocusNames=b3469, JW3434; OS Escherichia coli (strain K12). OC Bacteria; Pseudomonadota; Gammaproteobacteria; Enterobacterales; OC Enterobacteriaceae; Escherichia. OX NCBI_TaxID=83333; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=K12 / MG1655 / ATCC 47076; RX PubMed=8041620; DOI=10.1093/nar/22.13.2576; RA Sofia H.J., Burland V., Daniels D.L., Plunkett G. III, Blattner F.R.; RT "Analysis of the Escherichia coli genome. V. DNA sequence of the region RT from 76.0 to 81.5 minutes."; RL Nucleic Acids Res. 22:2576-2586(1994). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=K12 / MG1655 / ATCC 47076; RX PubMed=9278503; DOI=10.1126/science.277.5331.1453; RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., RA Shao Y.; RT "The complete genome sequence of Escherichia coli K-12."; RL Science 277:1453-1462(1997). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911; RX PubMed=16738553; DOI=10.1038/msb4100049; RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.; RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 RT and W3110."; RL Mol. Syst. Biol. 2:E1-E5(2006). RN [4] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, INDUCTION, AND RP DISRUPTION PHENOTYPE. RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911; RX PubMed=9405611; DOI=10.1073/pnas.94.26.14326; RA Rensing C., Mitra B., Rosen B.P.; RT "The zntA gene of Escherichia coli encodes a Zn(II)-translocating P-type RT ATPase."; RL Proc. Natl. Acad. Sci. U.S.A. 94:14326-14331(1997). RN [5] RP FUNCTION, AND DISRUPTION PHENOTYPE. RC STRAIN=K12 / MG1655 / ATCC 47076; RX PubMed=9364914; DOI=10.1111/j.1365-2958.1997.mmi518.x; RA Beard S.J., Hashim R., Membrillo-Hernandez J., Hughes M.N., Poole R.K.; RT "Zinc(II) tolerance in Escherichia coli K-12: evidence that the zntA gene RT (o732) encodes a cation transport ATPase."; RL Mol. Microbiol. 25:883-891(1997). RN [6] RP FUNCTION IN PB(2+) RESISTANCE, AND DISRUPTION PHENOTYPE. RX PubMed=9830000; DOI=10.1074/jbc.273.49.32614; RA Rensing C., Sun Y., Mitra B., Rosen B.P.; RT "Pb(II)-translocating P-type ATPases."; RL J. Biol. Chem. 273:32614-32617(1998). RN [7] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND RP SUBCELLULAR LOCATION. RX PubMed=10660539; DOI=10.1074/jbc.275.6.3873; RA Sharma R., Rensing C., Rosen B.P., Mitra B.; RT "The ATP hydrolytic activity of purified ZntA, a Pb(II)/Cd(II)/Zn(II)- RT translocating ATPase from Escherichia coli."; RL J. Biol. Chem. 275:3873-3878(2000). RN [8] RP TOPOLOGY [LARGE SCALE ANALYSIS], AND SUBCELLULAR LOCATION. RC STRAIN=K12 / MG1655 / ATCC 47076; RX PubMed=15919996; DOI=10.1126/science.1109730; RA Daley D.O., Rapp M., Granseth E., Melen K., Drew D., von Heijne G.; RT "Global topology analysis of the Escherichia coli inner membrane RT proteome."; RL Science 308:1321-1323(2005). RN [9] RP SUBCELLULAR LOCATION, DOMAIN, METAL-BINDING SITES, AND MUTAGENESIS OF RP 59-CYS--CYS-62 AND 392-CYS--CYS-394. RX PubMed=16411752; DOI=10.1021/bi051836n; RA Liu J., Dutta S.J., Stemmler A.J., Mitra B.; RT "Metal-binding affinity of the transmembrane site in ZntA: implications for RT metal selectivity."; RL Biochemistry 45:763-772(2006). RN [10] RP SUBCELLULAR LOCATION, DOMAIN, METAL-BINDING SITES, AND MUTAGENESIS OF RP 59-CYS--CYS-62; 392-CYS--CYS-394; LYS-693 AND ASP-714. RX PubMed=16890908; DOI=10.1016/j.bbabio.2006.06.008; RA Okkeri J., Haltia T.; RT "The metal-binding sites of the zinc-transporting P-type ATPase of RT Escherichia coli. Lys693 and Asp714 in the seventh and eighth transmembrane RT segments of ZntA contribute to the coupling of metal binding and ATPase RT activity."; RL Biochim. Biophys. Acta 1757:1485-1495(2006). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, DOMAIN, RP METAL-BINDING SITES, AND MUTAGENESIS OF CYS-392; PRO-393 AND CYS-394. RX PubMed=17326661; DOI=10.1021/bi0616394; RA Dutta S.J., Liu J., Stemmler A.J., Mitra B.; RT "Conservative and nonconservative mutations of the transmembrane CPC motif RT in ZntA: effect on metal selectivity and activity."; RL Biochemistry 46:3692-3703(2007). RN [12] RP METAL-BINDING SITES. RX PubMed=22387457; DOI=10.1016/j.bbamem.2012.02.020; RA Raimunda D., Subramanian P., Stemmler T., Argueello J.M.; RT "A tetrahedral coordination of zinc during transmembrane transport by P- RT type Zn(2+)-ATPases."; RL Biochim. Biophys. Acta 1818:1374-1377(2012). RN [13] {ECO:0007744|PDB:1MWY, ECO:0007744|PDB:1MWZ} RP STRUCTURE BY NMR OF 46-118 IN APO AND ZINC-BOUND FORMS. RX PubMed=12417201; DOI=10.1016/s0022-2836(02)01007-0; RA Banci L., Bertini I., Ciofi-Baffoni S., Finney L.A., Outten C.E., RA O'Halloran T.V.; RT "A new zinc-protein coordination site in intracellular metal trafficking: RT solution structure of the Apo and Zn(II) forms of ZntA(46-118)."; RL J. Mol. Biol. 323:883-897(2002). CC -!- FUNCTION: Confers resistance to zinc, cadmium and lead (PubMed:9405611, CC PubMed:9364914, PubMed:9830000, PubMed:10660539, PubMed:17326661). CC Couples the hydrolysis of ATP with the export of zinc, cadmium or lead, CC with highest activity when the metals are present as metal-thiolate CC complexes (PubMed:9405611, PubMed:10660539, PubMed:17326661). Can also CC bind nickel, copper, cobalt and mercury (PubMed:10660539, CC PubMed:17326661). {ECO:0000269|PubMed:10660539, CC ECO:0000269|PubMed:17326661, ECO:0000269|PubMed:9364914, CC ECO:0000269|PubMed:9405611, ECO:0000269|PubMed:9830000}. CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O + Pb(2+)(in) = ADP + H(+) + Pb(2+)(out) + phosphate; CC Xref=Rhea:RHEA:52580, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, ChEBI:CHEBI:49807, CC ChEBI:CHEBI:456216; Evidence={ECO:0000269|PubMed:10660539, CC ECO:0000269|PubMed:17326661}; CC -!- CATALYTIC ACTIVITY: CC Reaction=ATP + H2O + Zn(2+)(in) = ADP + H(+) + phosphate + Zn(2+)(out); CC Xref=Rhea:RHEA:20621, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:29105, ChEBI:CHEBI:30616, ChEBI:CHEBI:43474, CC ChEBI:CHEBI:456216; EC=7.2.2.12; CC Evidence={ECO:0000269|PubMed:10660539, ECO:0000269|PubMed:17326661, CC ECO:0000269|PubMed:9405611}; 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:10660539, ECO:0000269|PubMed:17326661, CC ECO:0000269|PubMed:9405611}; CC -!- ACTIVITY REGULATION: Inhibited by orthovanadate. CC {ECO:0000269|PubMed:9405611}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=6.9 uM for Pb(2+) (at 37 degrees Celsius and pH 7.0) CC {ECO:0000269|PubMed:10660539}; CC KM=6.1 uM for Pb(2+) (at 37 degrees Celsius and pH 7.0) CC {ECO:0000269|PubMed:17326661}; CC KM=118 uM for Pb(2+)-thiolate (at 37 degrees Celsius and pH 7.0) CC {ECO:0000269|PubMed:10660539}; CC KM=150 uM for Pb(2+)-thiolate (at 37 degrees Celsius and pH 7.0) CC {ECO:0000269|PubMed:17326661}; CC KM=5.1 uM for Zn(2+) (at 37 degrees Celsius and pH 7.0) CC {ECO:0000269|PubMed:10660539, ECO:0000269|PubMed:17326661}; CC KM=109 uM for Zn(2+)-thiolate (at 37 degrees Celsius and pH 7.0) CC {ECO:0000269|PubMed:10660539}; CC KM=105 uM for Zn(2+)-thiolate (at 37 degrees Celsius and pH 7.0) CC {ECO:0000269|PubMed:17326661}; CC KM=3.1 uM for Cd(2+) (at 37 degrees Celsius and pH 7.0) CC {ECO:0000269|PubMed:17326661}; CC KM=115 uM for Cd(2+)-thiolate (at 37 degrees Celsius and pH 7.0) CC {ECO:0000269|PubMed:10660539}; CC KM=123 uM for Cd(2+)-thiolate (at 37 degrees Celsius and pH 7.0) CC {ECO:0000269|PubMed:17326661}; CC KM=3.4 uM for Cu(2+) (at 37 degrees Celsius and pH 7.0) CC {ECO:0000269|PubMed:17326661}; CC KM=85 uM for Cu(2+)-thiolate (at 37 degrees Celsius and pH 7.0) CC {ECO:0000269|PubMed:17326661}; CC KM=2.1 uM for Ni(2+) (at 37 degrees Celsius and pH 7.0) CC {ECO:0000269|PubMed:17326661}; CC KM=169 uM for Ni(2+)-thiolate (at 37 degrees Celsius and pH 7.0) CC {ECO:0000269|PubMed:17326661}; CC KM=4 uM for Co(2+) (at 37 degrees Celsius and pH 7.0) CC {ECO:0000269|PubMed:17326661}; CC KM=75 uM for Co(2+)-thiolate (at 37 degrees Celsius and pH 7.0) CC {ECO:0000269|PubMed:17326661}; CC Vmax=0.88 umol/min/mg enzyme with Pb(2+) as substrate (at 37 degrees CC Celsius and pH 7.0) {ECO:0000269|PubMed:10660539}; CC Vmax=0.638 umol/min/mg enzyme with Pb(2+) as substrate (at 37 degrees CC Celsius and pH 7.0) {ECO:0000269|PubMed:17326661}; CC Vmax=3.02 umol/min/mg enzyme with Pb(2+)-thiolate as substrate (at 37 CC degrees Celsius and pH 7.0) {ECO:0000269|PubMed:10660539}; CC Vmax=2.497 umol/min/mg enzyme with Pb(2+)-thiolate as substrate (at CC 37 degrees Celsius and pH 7.0) {ECO:0000269|PubMed:17326661}; CC Vmax=0.19 umol/min/mg enzyme with Zn(2+) as substrate (at 37 degrees CC Celsius and pH 7.0) {ECO:0000269|PubMed:10660539}; CC Vmax=0.21 umol/min/mg enzyme with Zn(2+) as substrate (at 37 degrees CC Celsius and pH 7.0) {ECO:0000269|PubMed:17326661}; CC Vmax=0.96 umol/min/mg enzyme with Zn(2+)-thiolate as substrate (at 37 CC degrees Celsius and pH 7.0) {ECO:0000269|PubMed:10660539}; CC Vmax=0.932 umol/min/mg enzyme with Zn(2+)-thiolate as substrate (at CC 37 degrees Celsius and pH 7.0) {ECO:0000269|PubMed:17326661}; CC Vmax=0.102 umol/min/mg enzyme with Cd(2+) as substrate (at 37 degrees CC Celsius and pH 7.0) {ECO:0000269|PubMed:17326661}; CC Vmax=1.16 umol/min/mg enzyme with Cd(2+)-thiolate as substrate (at 37 CC degrees Celsius and pH 7.0) {ECO:0000269|PubMed:10660539}; CC Vmax=0.862 umol/min/mg enzyme with Cd(2+)-thiolate as substrate (at CC 37 degrees Celsius and pH 7.0) {ECO:0000269|PubMed:17326661}; CC Vmax=0.085 umol/min/mg enzyme with Cu(2+) as substrate (at 37 degrees CC Celsius and pH 7.0) {ECO:0000269|PubMed:17326661}; CC Vmax=0.104 umol/min/mg enzyme with Cu(2+)-thiolate as substrate (at CC 37 degrees Celsius and pH 7.0) {ECO:0000269|PubMed:17326661}; CC Vmax=0.076 umol/min/mg enzyme with Ni(2+) as substrate (at 37 degrees CC Celsius and pH 7.0) {ECO:0000269|PubMed:17326661}; CC Vmax=0.138 umol/min/mg enzyme with Ni(2+)-thiolate as substrate (at CC 37 degrees Celsius and pH 7.0) {ECO:0000269|PubMed:17326661}; CC Vmax=0.036 umol/min/mg enzyme with Co(2+) as substrate (at 37 degrees CC Celsius and pH 7.0) {ECO:0000269|PubMed:17326661}; CC Vmax=0.103 umol/min/mg enzyme with Co(2+)-thiolate as substrate (at CC 37 degrees Celsius and pH 7.0) {ECO:0000269|PubMed:17326661}; CC -!- SUBCELLULAR LOCATION: Cell inner membrane {ECO:0000269|PubMed:10660539, CC ECO:0000269|PubMed:15919996, ECO:0000269|PubMed:16411752, CC ECO:0000269|PubMed:16890908}; Multi-pass membrane protein CC {ECO:0000255}. CC -!- INDUCTION: Induced by zinc. {ECO:0000269|PubMed:9405611}. CC -!- DOMAIN: Has two high-affinity metal-binding sites, one in the N- CC terminal region and another in the transmembrane region. Both sites are CC able to access and bind metal ion independently of each other. The N- CC terminal metal-binding site is not strictly necessary for activity and CC metal selectivity, but is needed for maximal activity and may be CC involved in regulation. The metal-binding site in the transmembrane CC region is essential for activity of the pump. CC {ECO:0000269|PubMed:16411752, ECO:0000269|PubMed:16890908, CC ECO:0000269|PubMed:17326661}. CC -!- DISRUPTION PHENOTYPE: Mutant exhibits hypersensitivity to zinc, CC cadmium, lead and, to a lesser extent, cobalt and nickel. CC {ECO:0000269|PubMed:9364914, ECO:0000269|PubMed:9405611, CC ECO:0000269|PubMed:9830000}. CC -!- SIMILARITY: Belongs to the cation transport ATPase (P-type) (TC 3.A.3) CC family. Type IB 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; U00039; AAB18444.1; -; Genomic_DNA. DR EMBL; U00096; AAC76494.1; -; Genomic_DNA. DR EMBL; AP009048; BAE77824.1; -; Genomic_DNA. DR PIR; S47688; S47688. DR RefSeq; NP_417926.1; NC_000913.3. DR RefSeq; WP_000106551.1; NZ_SSZK01000008.1. DR PDB; 1MWY; NMR; -; A=46-118. DR PDB; 1MWZ; NMR; -; A=46-118. DR PDBsum; 1MWY; -. DR PDBsum; 1MWZ; -. DR AlphaFoldDB; P37617; -. DR BMRB; P37617; -. DR SMR; P37617; -. DR BioGRID; 4262921; 26. DR DIP; DIP-12947N; -. DR IntAct; P37617; 8. DR STRING; 511145.b3469; -. DR TCDB; 3.A.3.6.2; the p-type atpase (p-atpase) superfamily. DR jPOST; P37617; -. DR PaxDb; 511145-b3469; -. DR EnsemblBacteria; AAC76494; AAC76494; b3469. DR GeneID; 947972; -. DR KEGG; ecj:JW3434; -. DR KEGG; eco:b3469; -. DR PATRIC; fig|1411691.4.peg.3256; -. DR EchoBASE; EB2129; -. DR eggNOG; COG2217; Bacteria. DR HOGENOM; CLU_001771_6_4_6; -. DR InParanoid; P37617; -. DR OMA; SFDEWIY; -. DR OrthoDB; 9814270at2; -. DR PhylomeDB; P37617; -. DR BioCyc; EcoCyc:YHHO-MONOMER; -. DR BioCyc; MetaCyc:YHHO-MONOMER; -. DR SABIO-RK; P37617; -. DR EvolutionaryTrace; P37617; -. DR PRO; PR:P37617; -. DR Proteomes; UP000000318; Chromosome. DR Proteomes; UP000000625; Chromosome. DR GO; GO:0016020; C:membrane; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; IDA:EcoCyc. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0016887; F:ATP hydrolysis activity; ISA:EcoliWiki. DR GO; GO:0015086; F:cadmium ion transmembrane transporter activity; IBA:GO_Central. DR GO; GO:0015094; F:lead ion transmembrane transporter activity; IMP:EcoCyc. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0008551; F:P-type cadmium transporter activity; IDA:EcoCyc. DR GO; GO:0016463; F:P-type zinc transporter activity; IDA:EcoCyc. DR GO; GO:0070574; P:cadmium ion transmembrane transport; IDA:EcoCyc. DR GO; GO:0010312; P:detoxification of zinc ion; IMP:EcoliWiki. DR GO; GO:0006882; P:intracellular zinc ion homeostasis; IC:EcoCyc. DR GO; GO:0015692; P:lead ion transport; IMP:EcoCyc. DR GO; GO:0030001; P:metal ion transport; IBA:GO_Central. DR GO; GO:0046686; P:response to cadmium ion; IMP:EcoCyc. DR GO; GO:0010288; P:response to lead ion; IEP:EcoCyc. DR GO; GO:0010043; P:response to zinc ion; IMP:EcoCyc. DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central. DR GO; GO:0071577; P:zinc ion transmembrane transport; IDA:EcoCyc. DR GO; GO:0006829; P:zinc ion transport; IMP:EcoliWiki. DR CDD; cd00371; HMA; 1. DR CDD; cd07546; P-type_ATPase_Pb_Zn_Cd2-like; 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; 1.20.1110.10; Calcium-transporting ATPase, transmembrane domain; 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; 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; TIGR01512; ATPase-IB2_Cd; 1. DR NCBIfam; TIGR01525; ATPase-IB_hvy; 1. DR NCBIfam; TIGR01494; ATPase_P-type; 1. DR PANTHER; PTHR48085; CADMIUM/ZINC-TRANSPORTING ATPASE HMA2-RELATED; 1. DR PANTHER; PTHR48085:SF5; CADMIUM_ZINC-TRANSPORTING ATPASE HMA2; 1. DR Pfam; PF00122; E1-E2_ATPase; 1. DR Pfam; PF00403; HMA; 1. DR Pfam; PF00702; Hydrolase; 1. DR PRINTS; PR00119; CATATPASE. DR PRINTS; PR00120; HATPASE. 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 3D-structure; ATP-binding; Cadmium; Cell inner membrane; Cell membrane; KW Ion transport; Lead; Magnesium; Membrane; Metal-binding; KW Nucleotide-binding; Phosphoprotein; Reference proteome; Translocase; KW Transmembrane; Transmembrane helix; Transport; Zinc; Zinc transport. FT CHAIN 1..732 FT /note="Zinc/cadmium/lead-transporting P-type ATPase" FT /id="PRO_0000046332" FT TOPO_DOM 1..124 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 125..145 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 146 FT /note="Periplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 147..167 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 168..179 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 180..197 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 198..202 FT /note="Periplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 203..222 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 223..356 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 357..377 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 378..383 FT /note="Periplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 384..404 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 405..685 FT /note="Cytoplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 686..702 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 703..707 FT /note="Periplasmic" FT /evidence="ECO:0000305" FT TRANSMEM 708..729 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 730..732 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:15919996" FT DOMAIN 48..112 FT /note="HMA" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT ACT_SITE 436 FT /note="4-aspartylphosphate intermediate" FT /evidence="ECO:0000250|UniProtKB:Q3YW59" FT BINDING 58 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:12417201" FT BINDING 59 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280, FT ECO:0000269|PubMed:12417201, ECO:0000305|PubMed:16411752, FT ECO:0000305|PubMed:16890908" FT BINDING 62 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280, FT ECO:0000269|PubMed:12417201, ECO:0000305|PubMed:16411752, FT ECO:0000305|PubMed:16890908" FT BINDING 392 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000305|PubMed:16411752, FT ECO:0000305|PubMed:16890908, ECO:0000305|PubMed:17326661, FT ECO:0000305|PubMed:22387457" FT BINDING 394 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000305|PubMed:16411752, FT ECO:0000305|PubMed:16890908, ECO:0000305|PubMed:17326661, FT ECO:0000305|PubMed:22387457" FT BINDING 436 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:Q3YW59" FT BINDING 438 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:Q3YW59" FT BINDING 628 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:Q3YW59" FT BINDING 714 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000305|PubMed:16890908, FT ECO:0000305|PubMed:22387457" FT SITE 693 FT /note="Important for metal transport" FT /evidence="ECO:0000250|UniProtKB:Q3YW59, FT ECO:0000305|PubMed:16890908, ECO:0000305|PubMed:22387457" FT MUTAGEN 59..62 FT /note="CAAC->AAAA: 2-3-fold decrease in ATPase activity. FT Binds metal ion only at the transmembrane site." FT /evidence="ECO:0000269|PubMed:16411752" FT MUTAGEN 59..62 FT /note="CAAC->SAAS: Reduces the ATPase activity by 50%. FT Reduces level of phosphorylation." FT /evidence="ECO:0000269|PubMed:16890908" FT MUTAGEN 392..394 FT /note="CPC->APA: Lack of ATPase activity. Binds metal ion FT only at the N-terminal site." FT /evidence="ECO:0000269|PubMed:16411752" FT MUTAGEN 392..394 FT /note="CPC->SPS: Lack of ATPase activity. Loss of FT zinc-stimulated phosphorylation." FT /evidence="ECO:0000269|PubMed:16890908" FT MUTAGEN 392 FT /note="C->A: Lack of activity. Cannot bind metal at the FT transmembrane site. Lack of phosphorylation with ATP." FT /evidence="ECO:0000269|PubMed:17326661" FT MUTAGEN 392 FT /note="C->H,S: Decrease in activity. Binds Zn(2+), Cd(2+), FT Ni(2+), Co(2+) and Cu(2+), but not Pb(2+)." FT /evidence="ECO:0000269|PubMed:17326661" FT MUTAGEN 393 FT /note="P->A: Lack of activity with any metal. Cannot bind FT metal at the transmembrane site. Lack of phosphorylation FT with ATP." FT /evidence="ECO:0000269|PubMed:17326661" FT MUTAGEN 394 FT /note="C->A: Lack of activity. Cannot bind metal at the FT transmembrane site. Lack of phosphorylation with ATP." FT /evidence="ECO:0000269|PubMed:17326661" FT MUTAGEN 394 FT /note="C->H,S: Decrease in activity. Binds Zn(2+), Cd(2+), FT Ni(2+), Co(2+) and Cu(2+), but not Pb(2+)." FT /evidence="ECO:0000269|PubMed:17326661" FT MUTAGEN 693 FT /note="K->N: Loss of zinc-stimulated ATPase activity. FT Poorly phosphorylated with ATP." FT /evidence="ECO:0000269|PubMed:16890908" FT MUTAGEN 714 FT /note="D->M: Shows high metal-independent ATPase activity. FT Poorly phosphorylated with ATP." FT /evidence="ECO:0000269|PubMed:16890908" FT STRAND 48..56 FT /evidence="ECO:0007829|PDB:1MWY" FT HELIX 62..71 FT /evidence="ECO:0007829|PDB:1MWY" FT STRAND 73..82 FT /evidence="ECO:0007829|PDB:1MWY" FT TURN 83..86 FT /evidence="ECO:0007829|PDB:1MWY" FT STRAND 87..94 FT /evidence="ECO:0007829|PDB:1MWY" FT HELIX 97..107 FT /evidence="ECO:0007829|PDB:1MWY" FT STRAND 110..113 FT /evidence="ECO:0007829|PDB:1MWY" SQ SEQUENCE 732 AA; 76840 MW; 25476EA830786465 CRC64; MSTPDNHGKK APQFAAFKPL TTVQNANDCC CDGACSSTPT LSENVSGTRY SWKVSGMDCA ACARKVENAV RQLAGVNQVQ VLFATEKLVV DADNDIRAQV ESALQKAGYS LRDEQAAEEP QASRLKENLP LITLIVMMAI SWGLEQFNHP FGQLAFIATT LVGLYPIARQ ALRLIKSGSY FAIETLMSVA AIGALFIGAT AEAAMVLLLF LIGERLEGWA ASRARQGVSA LMALKPETAT RLRKGEREEV AINSLRPGDV IEVAAGGRLP ADGKLLSPFA SFDESALTGE SIPVERATGD KVPAGATSVD RLVTLEVLSE PGASAIDRIL KLIEEAEERR APIERFIDRF SRIYTPAIMA VALLVTLVPP LLFAASWQEW IYKGLTLLLI GCPCALVIST PAAITSGLAA AARRGALIKG GAALEQLGRV TQVAFDKTGT LTVGKPRVTA IHPATGISES ELLTLAAAVE QGATHPLAQA IVREAQVAEL AIPTAESQRA LVGSGIEAQV NGERVLICAA GKHPADAFTG LINELESAGQ TVVLVVRNDD VLGVIALQDT LRADAATAIS ELNALGVKGV ILTGDNPRAA AAIAGELGLE FKAGLLPEDK VKAVTELNQH APLAMVGDGI NDAPAMKAAA IGIAMGSGTD VALETADAAL THNHLRGLVQ MIELARATHA NIRQNITIAL GLKGIFLVTT LLGMTGLWLA VLADTGATVL VTANALRLLR RR //