ID HMCT_HELPY Reviewed; 686 AA. AC Q59465; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 2. DT 27-MAR-2024, entry version 163. DE RecName: Full=Cadmium, zinc and cobalt-transporting ATPase; DE EC=7.2.2.12; DE EC=7.2.2.21; GN Name=cadA; OrderedLocusNames=HP_0791; OS Helicobacter pylori (strain ATCC 700392 / 26695) (Campylobacter pylori). OC Bacteria; Campylobacterota; Epsilonproteobacteria; Campylobacterales; OC Helicobacteraceae; Helicobacter. OX NCBI_TaxID=85962; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=69A; RX PubMed=8550601; DOI=10.1074/jbc.271.1.446; RA Melchers K., Weitzenegger T., Buhmann A., Steinhilber W., Sachs G., RA Schaefer K.P.; RT "Cloning and membrane topology of a P type ATPase from Helicobacter RT pylori."; RL J. Biol. Chem. 271:446-457(1996). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 700392 / 26695; RX PubMed=9252185; DOI=10.1038/41483; RA Tomb J.-F., White O., Kerlavage A.R., Clayton R.A., Sutton G.G., RA Fleischmann R.D., Ketchum K.A., Klenk H.-P., Gill S.R., Dougherty B.A., RA Nelson K.E., Quackenbush J., Zhou L., Kirkness E.F., Peterson S.N., RA Loftus B.J., Richardson D.L., Dodson R.J., Khalak H.G., Glodek A., RA McKenney K., FitzGerald L.M., Lee N., Adams M.D., Hickey E.K., Berg D.E., RA Gocayne J.D., Utterback T.R., Peterson J.D., Kelley J.M., Cotton M.D., RA Weidman J.F., Fujii C., Bowman C., Watthey L., Wallin E., Hayes W.S., RA Borodovsky M., Karp P.D., Smith H.O., Fraser C.M., Venter J.C.; RT "The complete genome sequence of the gastric pathogen Helicobacter RT pylori."; RL Nature 388:539-547(1997). RN [3] RP TOPOLOGY. RC STRAIN=69A; RX PubMed=10417643; DOI=10.1046/j.1365-2958.1999.01496.x; RA Herrmann L., Schwan D., Garner R., Mobley H.L., Haas R., Schaefer K.P., RA Melchers K.; RT "Helicobacter pylori cadA encodes an essential Cd(II)-Zn(II)-Co(II) RT resistance factor influencing urease activity."; RL Mol. Microbiol. 33:524-536(1999). RN [4] RP SUBSTRATE SPECIFICITY. RC STRAIN=69A; RX PubMed=10577484; DOI=10.1016/s0923-2508(99)00106-0; RA Melchers K., Schuhmacher A., Buhmann A., Weitzenegger T., Belin D., RA Grau S., Ehrmann M.; RT "Membrane topology of CadA homologous P-type ATPase of Helicobacter pylori RT as determined by expression of phoA fusions in Escherichia coli and the RT positive inside rule."; RL Res. Microbiol. 150:507-520(1999). CC -!- FUNCTION: Couples the hydrolysis of ATP with the transport of cadmium, CC zinc and cobalt out of the cell. This ion efflux may influence the CC activity of urease, which is essential for the survival of the CC bacterium in the gastric environment. 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 -!- 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 -!- SUBCELLULAR LOCATION: Cell membrane; Multi-pass membrane protein. 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; L46864; AAA93043.1; -; Genomic_DNA. DR EMBL; AE000511; AAD07839.1; -; Genomic_DNA. DR PIR; G64618; G64618. DR RefSeq; NP_207584.1; NC_000915.1. DR RefSeq; WP_001158808.1; NC_018939.1. DR AlphaFoldDB; Q59465; -. DR SMR; Q59465; -. DR DIP; DIP-3082N; -. DR IntAct; Q59465; 3. DR MINT; Q59465; -. DR STRING; 85962.HP_0791; -. DR TCDB; 3.A.3.6.3; the p-type atpase (p-atpase) superfamily. DR PaxDb; 85962-C694_04055; -. DR DNASU; 899347; -. DR EnsemblBacteria; AAD07839; AAD07839; HP_0791. DR KEGG; hpy:HP_0791; -. DR PATRIC; fig|85962.47.peg.843; -. DR eggNOG; COG2217; Bacteria. DR InParanoid; Q59465; -. DR OrthoDB; 2490525at2; -. DR PhylomeDB; Q59465; -. DR Proteomes; UP000000429; Chromosome. DR GO; GO:0016020; C:membrane; IBA:GO_Central. DR GO; GO:0005886; C:plasma 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:0015086; F:cadmium ion transmembrane transporter activity; IBA:GO_Central. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0008551; F:P-type cadmium transporter activity; IEA:UniProtKB-EC. DR GO; GO:0016463; F:P-type zinc transporter activity; IEA:UniProtKB-EC. DR GO; GO:0030001; P:metal ion transport; IMP:CACAO. DR GO; GO:0055085; P:transmembrane transport; IBA:GO_Central. DR CDD; cd00371; HMA; 1. DR CDD; cd07548; P-type_ATPase-Cd_Zn_Co_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; 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; PR00941; CDATPASE. 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; Cadmium; Cell membrane; Cobalt; Magnesium; Membrane; KW Metal-binding; Nucleotide-binding; Phosphoprotein; Reference proteome; KW Translocase; Transmembrane; Transmembrane helix; Zinc. FT CHAIN 1..686 FT /note="Cadmium, zinc and cobalt-transporting ATPase" FT /id="PRO_0000046176" FT TOPO_DOM 1..72 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:10417643" FT TRANSMEM 73..92 FT /note="Helical; Name=1" FT TOPO_DOM 93..102 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:10417643" FT TRANSMEM 103..124 FT /note="Helical; Name=2" FT TOPO_DOM 125..131 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:10417643" FT TRANSMEM 132..151 FT /note="Helical; Name=3" FT TOPO_DOM 152..154 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:10417643" FT TRANSMEM 155..174 FT /note="Helical; Name=4" FT TOPO_DOM 175..308 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:10417643" FT TRANSMEM 309..327 FT /note="Helical; Name=5" FT TOPO_DOM 328..332 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:10417643" FT TRANSMEM 333..350 FT /note="Helical; Name=6" FT TOPO_DOM 351..635 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:10417643" FT TRANSMEM 636..657 FT /note="Helical; Name=7" FT TOPO_DOM 658..665 FT /note="Extracellular" FT /evidence="ECO:0000269|PubMed:10417643" FT TRANSMEM 666..681 FT /note="Helical; Name=8" FT TOPO_DOM 682..686 FT /note="Cytoplasmic" FT /evidence="ECO:0000269|PubMed:10417643" FT DOMAIN 1..62 FT /note="HMA" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT ACT_SITE 388 FT /note="4-aspartylphosphate intermediate" FT /evidence="ECO:0000250" FT BINDING 11 FT /ligand="Cd(2+)" FT /ligand_id="ChEBI:CHEBI:48775" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT BINDING 11 FT /ligand="Co(2+)" FT /ligand_id="ChEBI:CHEBI:48828" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT BINDING 11 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT BINDING 14 FT /ligand="Cd(2+)" FT /ligand_id="ChEBI:CHEBI:48775" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT BINDING 14 FT /ligand="Co(2+)" FT /ligand_id="ChEBI:CHEBI:48828" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT BINDING 14 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00280" FT BINDING 583 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT BINDING 587 FT /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT VARIANT 24 FT /note="E -> K (in strain: 69A)" FT VARIANT 39 FT /note="K -> R (in strain: 69A)" FT VARIANT 69 FT /note="T -> A (in strain: 69A)" FT VARIANT 80 FT /note="I -> V (in strain: 69A)" FT VARIANT 83 FT /note="M -> A (in strain: 69A)" FT VARIANT 148 FT /note="F -> C (in strain: 69A)" FT VARIANT 173..174 FT /note="VS -> IA (in strain: 69A)" FT VARIANT 198 FT /note="E -> A (in strain: 69A)" FT VARIANT 209 FT /note="V -> I (in strain: 69A)" FT VARIANT 228 FT /note="V -> I (in strain: 69A)" FT VARIANT 251 FT /note="N -> R (in strain: 69A)" FT VARIANT 435 FT /note="K -> E (in strain: 69A)" FT VARIANT 456 FT /note="V -> L (in strain: 69A)" FT VARIANT 504 FT /note="V -> I (in strain: 69A)" FT VARIANT 526 FT /note="V -> A (in strain: 69A)" FT VARIANT 555 FT /note="H -> Y (in strain: 69A)" SQ SEQUENCE 686 AA; 75012 MW; 8777A49D80397E19 CRC64; MQEYHIHNLD CPDCASKLER DLNELDYVKK AQINFSTSKL FLDTSDFEKV KAFIKQNEPH LSLSFKEATE KPLSFTPLII TIMVFLGAIL ILHLNPSPLI EKAMFFVLAL VYLVSGKDVI LGAFRGLRKG QFFDENALML IATIAAFFVG AYEESVSIMV FYSAGEFLQK LAVSRSKKSL KALVDVAPNL AYLKKGDELV SVAPEDLRVN DIVVVKVGEK VPVDGVVVKG ESLLDERALS GESMPVNVSE NSKVLGGSLN LKAVLEIQVE KMYKDSSIAK VVDLVQQATN EKSETEKFIT KFSRYYTPSV LFIALMIAVL PPLFSMGSFD EWIYRGLVAL MVSCPCALVI SVPLGYFGGV GAASRKGILM KGVHVLEVLT QAKSIAFDKT GTLTKGVFKV TDIVPQNGHS KEEVLHYASC SQLLSTHPIA LSIQKACEEM LKDDKHQHDI KNYEEVSGMG VKAQCHTDLI IAGNEKMLDQ FHIAHSPSKE NGTIVHVAFN QTYVGYIVIS DEIKDDAIEC LRDLKVQGIE NFCILSGDRK SATESIAQTL GCEYHASLLP EEKTSVFKTF KERYKAPAIF VGDGINDAPT LASADVGIGM GKGSELSKQS ADIVITNDSL NSLVKVLAIA KKTKSIIWQN ILFALGIKAV FIVLGLMGVA SLWEAVFGDV GVTLLALANS MRAMRA //