{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"A0A0H3GPN8","uniProtkbId":"CPXA_KLEPH","entryAudit":{"firstPublicDate":"2024-03-27","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2015-09-16","entryVersion":53,"sequenceVersion":1},"annotationScore":4.0,"organism":{"scientificName":"Klebsiella pneumoniae subsp. pneumoniae (strain HS11286)","taxonId":1125630,"evidences":[{"evidenceCode":"ECO:0000312","source":"Proteomes","id":"UP000007841"}],"lineage":["Bacteria","Pseudomonadati","Pseudomonadota","Gammaproteobacteria","Enterobacterales","Enterobacteriaceae","Klebsiella","Klebsiella pneumoniae complex"]},"proteinExistence":"2: Evidence at transcript level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"22496764"}],"value":"Sensor histidine kinase CpxA"},"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P0AE82"}],"value":"2.7.13.3"}]}},"genes":[{"geneName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"22496764"}],"value":"cpxA"},"orderedLocusNames":[{"evidences":[{"evidenceCode":"ECO:0000312","source":"EMBL","id":"AEW58769.1"}],"value":"KPHS_00710"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P0AE82"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22496764"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36898943"}],"value":"Histidine kinase member of the two-component regulatory system CpxA/CpxR which responds to envelope stress response by activating or, in some cases, repressing expression of downstream genes (PubMed:22496764, PubMed:36898943). Activates CpxR by phosphorylation (By similarity)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"ATP + protein L-histidine = ADP + protein N-phospho-L-histidine.","ecNumber":"2.7.13.3","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P0AE82"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P0AE82"}],"value":"The two-component system is activated by envelope stress such as overexpression of some (misfolded) periplasmic proteins"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P0AE88"}],"value":"Interacts with cognate response regulator CpxR"}],"commentType":"SUBUNIT"},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P0AE82"}],"value":"Cell inner membrane","id":"SL-0037"},"topology":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P0AE82"}],"value":"Multi-pass membrane protein","id":"SL-9909"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22496764"}],"value":"Part of the putative cpxR-cpxA operon"}],"commentType":"INDUCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22496764"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26385366"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"36898943"}],"value":"Deletion in the CG43 strain significantly increases FimA production but slightly decreases MrkA production (PubMed:36898943). A double cpxR-cpxA mutant in the CG43 strain activates expression of pecS and pecM (PubMed:26385366). Increases production of the major pilin of type 3 fimbriae MrkA as well as that of type 1 fimbriae FimA (PubMed:26385366, PubMed:36898943). Increases mannose-sensitive yeast agglutination activity and reduces biofilm formation in the CG43 strain (PubMed:26385366, PubMed:36898943). Increases promoter activities of fimA, fimB and mrkA, decreases ryhB and cpxP, but has no effect on fur (PubMed:36898943). A double cpxR-cpxA mutant in the NTUH-K2044 strain causes growth of smaller colonies, but no significant difference in cell size, compared to wild type (PubMed:22496764). Reduces growth in response to oxidative stress, osmotic or bile stressors (PubMed:22496764). Significantly reduces expression of the resistance-nodulation-cell division (RND) efflux pump genes, including acrB, acrD and eefB (PubMed:22496764). Significantly increases sensitivity to beta-lactam antibiotics, by comparison with wild type (PubMed:22496764). Halves survival rate upon exposure to the disinfectant, chlorhexidine (PubMed:22496764)"}],"commentType":"DISRUPTION PHENOTYPE"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":453,"modifier":"EXACT"}},"description":"Sensor histidine kinase CpxA","featureId":"PRO_0000459746"},{"type":"Topological domain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":4,"modifier":"EXACT"}},"description":"Cytoplasmic","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P0AE82"}]},{"type":"Transmembrane","location":{"start":{"value":5,"modifier":"EXACT"},"end":{"value":25,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Topological domain","location":{"start":{"value":26,"modifier":"EXACT"},"end":{"value":159,"modifier":"EXACT"}},"description":"Periplasmic","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P0AE82"}]},{"type":"Transmembrane","location":{"start":{"value":160,"modifier":"EXACT"},"end":{"value":180,"modifier":"EXACT"}},"description":"Helical","evidences":[{"evidenceCode":"ECO:0000255"}]},{"type":"Topological domain","location":{"start":{"value":181,"modifier":"EXACT"},"end":{"value":453,"modifier":"EXACT"}},"description":"Cytoplasmic","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P0AE82"}]},{"type":"Domain","location":{"start":{"value":180,"modifier":"EXACT"},"end":{"value":233,"modifier":"EXACT"}},"description":"HAMP","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00102"}]},{"type":"Domain","location":{"start":{"value":241,"modifier":"EXACT"},"end":{"value":451,"modifier":"EXACT"}},"description":"Histidine kinase","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00107"}]},{"type":"Active site","location":{"start":{"value":244,"modifier":"EXACT"},"end":{"value":244,"modifier":"EXACT"}},"description":"Nucleophile","evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P0AE82"}]},{"type":"Binding site","location":{"start":{"value":244,"modifier":"EXACT"},"end":{"value":247,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:30616"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P0AE82"}],"ligand":{"name":"ATP","id":"ChEBI:CHEBI:30616"}},{"type":"Binding site","location":{"start":{"value":355,"modifier":"EXACT"},"end":{"value":360,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:30616"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P0AE82"}],"ligand":{"name":"ATP","id":"ChEBI:CHEBI:30616"}},{"type":"Binding site","location":{"start":{"value":382,"modifier":"EXACT"},"end":{"value":382,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:30616"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P0AE82"}],"ligand":{"name":"ATP","id":"ChEBI:CHEBI:30616"}},{"type":"Binding site","location":{"start":{"value":401,"modifier":"EXACT"},"end":{"value":402,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:30616"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P0AE82"}],"ligand":{"name":"ATP","id":"ChEBI:CHEBI:30616"}},{"type":"Binding site","location":{"start":{"value":412,"modifier":"EXACT"},"end":{"value":417,"modifier":"EXACT"}},"description":"","featureCrossReferences":[{"database":"ChEBI","id":"CHEBI:30616"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P0AE82"}],"ligand":{"name":"ATP","id":"ChEBI:CHEBI:30616"}},{"type":"Modified residue","location":{"start":{"value":244,"modifier":"EXACT"},"end":{"value":244,"modifier":"EXACT"}},"description":"Phosphohistidine; by autocatalysis","evidences":[{"evidenceCode":"ECO:0000255","source":"PROSITE-ProRule","id":"PRU00107"}]}],"keywords":[{"id":"KW-0067","category":"Ligand","name":"ATP-binding"},{"id":"KW-0130","category":"Biological process","name":"Cell adhesion"},{"id":"KW-0997","category":"Cellular component","name":"Cell inner membrane"},{"id":"KW-1003","category":"Cellular component","name":"Cell membrane"},{"id":"KW-0418","category":"Molecular function","name":"Kinase"},{"id":"KW-0472","category":"Cellular component","name":"Membrane"},{"id":"KW-0547","category":"Ligand","name":"Nucleotide-binding"},{"id":"KW-0597","category":"PTM","name":"Phosphoprotein"},{"id":"KW-1185","category":"Technical term","name":"Reference proteome"},{"id":"KW-0808","category":"Molecular function","name":"Transferase"},{"id":"KW-0812","category":"Domain","name":"Transmembrane"},{"id":"KW-1133","category":"Domain","name":"Transmembrane helix"},{"id":"KW-0902","category":"Biological process","name":"Two-component regulatory system"}],"references":[{"referenceNumber":1,"citation":{"id":"22408243","citationType":"journal article","authors":["Liu P.","Li P.","Jiang X.","Bi D.","Xie Y.","Tai C.","Deng Z.","Rajakumar K.","Ou H.Y."],"citationCrossReferences":[{"database":"PubMed","id":"22408243"},{"database":"DOI","id":"10.1128/jb.00043-12"}],"title":"Complete genome sequence of Klebsiella pneumoniae subsp. pneumoniae HS11286, a multidrug-resistant strain isolated from human sputum.","publicationDate":"2012","journal":"J. Bacteriol.","firstPage":"1841","lastPage":"1842","volume":"194"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"referenceComments":[{"evidences":[{"evidenceCode":"ECO:0000312","source":"Proteomes","id":"UP000007841"}],"value":"HS11286","type":"STRAIN"}],"evidences":[{"evidenceCode":"ECO:0000312","source":"Proteomes","id":"UP000007841"}]},{"referenceNumber":2,"citation":{"id":"22496764","citationType":"journal article","authors":["Srinivasan V.B.","Vaidyanathan V.","Mondal A.","Rajamohan G."],"citationCrossReferences":[{"database":"PubMed","id":"22496764"},{"database":"DOI","id":"10.1371/journal.pone.0033777"}],"title":"Role of the two component signal transduction system CpxAR in conferring cefepime and chloramphenicol resistance in Klebsiella pneumoniae NTUH-K2044.","publicationDate":"2012","journal":"PLoS ONE","firstPage":"e33777","lastPage":"e33777","volume":"7"},"referencePositions":["FUNCTION","INDUCTION","DISRUPTION PHENOTYPE"],"referenceComments":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"NTUH-K2044","type":"STRAIN"}],"evidences":[{"evidenceCode":"ECO:0000305"}]},{"referenceNumber":3,"citation":{"id":"26385366","citationType":"journal article","authors":["Wang Z.C.","Liu C.J.","Huang Y.J.","Wang Y.S.","Peng H.L."],"citationCrossReferences":[{"database":"PubMed","id":"26385366"},{"database":"DOI","id":"10.1099/mic.0.000185"}],"title":"PecS regulates the urate-responsive expression of type 1 fimbriae in Klebsiella pneumoniae CG43.","publicationDate":"2015","journal":"Microbiology","firstPage":"2395","lastPage":"2409","volume":"161"},"referencePositions":["FUNCTION","DISRUPTION PHENOTYPE"],"referenceComments":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"CG43","type":"STRAIN"}],"evidences":[{"evidenceCode":"ECO:0000305"}]},{"referenceNumber":4,"citation":{"id":"36898943","citationType":"journal article","authors":["Kuo C.H.","Lin W.F.","Liu C.J.","Wang Z.C.","Liu T.Y.","Peng H.L."],"citationCrossReferences":[{"database":"PubMed","id":"36898943"},{"database":"DOI","id":"10.1016/j.jmii.2023.02.003"}],"title":"Role of the stress-responsive two-component system CpxAR in regulating fimbriae expression in Klebsiella pneumoniae CG43.","publicationDate":"2023","journal":"J. Microbiol. Immunol. Infect.","firstPage":"464","lastPage":"476","volume":"56"},"referencePositions":["FUNCTION","DISRUPTION PHENOTYPE"],"referenceComments":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"CG43","type":"STRAIN"}],"evidences":[{"evidenceCode":"ECO:0000305"}]}],"uniProtKBCrossReferences":[{"database":"EMBL","id":"CP003200","properties":[{"key":"ProteinId","value":"AEW58769.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"RefSeq","id":"WP_014342855.1","properties":[{"key":"NucleotideSequenceId","value":"NC_016845.1"}]},{"database":"RefSeq","id":"YP_005224371.1","properties":[{"key":"NucleotideSequenceId","value":"NC_016845.1"}]},{"database":"AlphaFoldDB","id":"A0A0H3GPN8","properties":[{"key":"Description","value":"-"}]},{"database":"SMR","id":"A0A0H3GPN8","properties":[{"key":"Description","value":"-"}]},{"database":"STRING","id":"1125630.KPHS_00710","properties":[{"key":"Description","value":"-"}]},{"database":"GeneID","id":"11845049","properties":[{"key":"Description","value":"-"}]},{"database":"KEGG","id":"kpm:KPHS_00710","properties":[{"key":"Description","value":"-"}]},{"database":"PATRIC","id":"fig|1125630.4.peg.71","properties":[{"key":"GeneDesignation","value":"-"}]},{"database":"HOGENOM","id":"CLU_000445_89_27_6","properties":[{"key":"Description","value":"-"}]},{"database":"Proteomes","id":"UP000007841","properties":[{"key":"Component","value":"Chromosome"}]},{"database":"GO","id":"GO:0005886","properties":[{"key":"GoTerm","value":"C:plasma membrane"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"GO","id":"GO:0000155","properties":[{"key":"GoTerm","value":"F:phosphorelay sensor kinase activity"},{"key":"GoEvidenceType","value":"IEA:InterPro"}]},{"database":"GO","id":"GO:0004673","properties":[{"key":"GoTerm","value":"F:protein histidine kinase activity"},{"key":"GoEvidenceType","value":"ISS:UniProtKB"}]},{"database":"CDD","id":"cd06225","properties":[{"key":"EntryName","value":"HAMP"},{"key":"MatchStatus","value":"1"}]},{"database":"CDD","id":"cd16949","properties":[{"key":"EntryName","value":"HATPase_CpxA-like"},{"key":"MatchStatus","value":"1"}]},{"database":"CDD","id":"cd00082","properties":[{"key":"EntryName","value":"HisKA"},{"key":"MatchStatus","value":"1"}]},{"database":"FunFam","id":"1.10.287.130:FF:000007","properties":[{"key":"EntryName","value":"Sensor histidine kinase CpxA"},{"key":"MatchStatus","value":"1"}]},{"database":"FunFam","id":"3.30.450.210:FF:000001","properties":[{"key":"EntryName","value":"Sensor histidine kinase CpxA"},{"key":"MatchStatus","value":"1"}]},{"database":"FunFam","id":"3.30.565.10:FF:000011","properties":[{"key":"EntryName","value":"Sensor histidine kinase CpxA"},{"key":"MatchStatus","value":"1"}]},{"database":"Gene3D","id":"1.10.287.130","properties":[{"key":"EntryName","value":"-"},{"key":"MatchStatus","value":"1"}]},{"database":"Gene3D","id":"3.30.565.10","properties":[{"key":"EntryName","value":"Histidine kinase-like ATPase, C-terminal domain"},{"key":"MatchStatus","value":"1"}]},{"database":"Gene3D","id":"3.30.450.210","properties":[{"key":"EntryName","value":"Two-component sensor protein CpxA, periplasmic domain"},{"key":"MatchStatus","value":"1"}]},{"database":"InterPro","id":"IPR058125","properties":[{"key":"EntryName","value":"CpxA"}]},{"database":"InterPro","id":"IPR058126","properties":[{"key":"EntryName","value":"CpxA-like_HATPase"}]},{"database":"InterPro","id":"IPR032404","properties":[{"key":"EntryName","value":"CpxA_peri"}]},{"database":"InterPro","id":"IPR038515","properties":[{"key":"EntryName","value":"CpxA_peri_sf"}]},{"database":"InterPro","id":"IPR003660","properties":[{"key":"EntryName","value":"HAMP_dom"}]},{"database":"InterPro","id":"IPR036890","properties":[{"key":"EntryName","value":"HATPase_C_sf"}]},{"database":"InterPro","id":"IPR003594","properties":[{"key":"EntryName","value":"HATPase_dom"}]},{"database":"InterPro","id":"IPR005467","properties":[{"key":"EntryName","value":"His_kinase_dom"}]},{"database":"InterPro","id":"IPR003661","properties":[{"key":"EntryName","value":"HisK_dim/P_dom"}]},{"database":"InterPro","id":"IPR036097","properties":[{"key":"EntryName","value":"HisK_dim/P_sf"}]},{"database":"InterPro","id":"IPR050398","properties":[{"key":"EntryName","value":"HssS/ArlS-like"}]},{"database":"InterPro","id":"IPR004358","properties":[{"key":"EntryName","value":"Sig_transdc_His_kin-like_C"}]},{"database":"NCBIfam","id":"NF007007","properties":[{"key":"EntryName","value":"PRK09470.1"},{"key":"MatchStatus","value":"1"}]},{"database":"PANTHER","id":"PTHR45528","properties":[{"key":"EntryName","value":"SENSOR HISTIDINE KINASE CPXA"},{"key":"MatchStatus","value":"1"}]},{"database":"PANTHER","id":"PTHR45528:SF1","properties":[{"key":"EntryName","value":"SENSOR HISTIDINE KINASE CPXA"},{"key":"MatchStatus","value":"1"}]},{"database":"Pfam","id":"PF16527","properties":[{"key":"EntryName","value":"CpxA_peri"},{"key":"MatchStatus","value":"1"}]},{"database":"Pfam","id":"PF00672","properties":[{"key":"EntryName","value":"HAMP"},{"key":"MatchStatus","value":"1"}]},{"database":"Pfam","id":"PF02518","properties":[{"key":"EntryName","value":"HATPase_c"},{"key":"MatchStatus","value":"1"}]},{"database":"Pfam","id":"PF00512","properties":[{"key":"EntryName","value":"HisKA"},{"key":"MatchStatus","value":"1"}]},{"database":"PRINTS","id":"PR00344","properties":[{"key":"EntryName","value":"BCTRLSENSOR"}]},{"database":"SMART","id":"SM00304","properties":[{"key":"EntryName","value":"HAMP"},{"key":"MatchStatus","value":"1"}]},{"database":"SMART","id":"SM00387","properties":[{"key":"EntryName","value":"HATPase_c"},{"key":"MatchStatus","value":"1"}]},{"database":"SMART","id":"SM00388","properties":[{"key":"EntryName","value":"HisKA"},{"key":"MatchStatus","value":"1"}]},{"database":"SUPFAM","id":"SSF55874","properties":[{"key":"EntryName","value":"ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase"},{"key":"MatchStatus","value":"1"}]},{"database":"SUPFAM","id":"SSF47384","properties":[{"key":"EntryName","value":"Homodimeric domain of signal transducing histidine kinase"},{"key":"MatchStatus","value":"1"}]},{"database":"PROSITE","id":"PS50885","properties":[{"key":"EntryName","value":"HAMP"},{"key":"MatchStatus","value":"1"}]},{"database":"PROSITE","id":"PS50109","properties":[{"key":"EntryName","value":"HIS_KIN"},{"key":"MatchStatus","value":"1"}]}],"sequence":{"value":"MTARIFAIFWLTLALVLMLVLMLPKLDSRQMTELLESEQRQGIMIEQHVEAELANDPPNDLMWWRRLFRAIDKWAPPGQRLLLVTSEGRVIGAERNEMQIIRNFIGQADNADHPQKKRYGRLEMVGPFSVRDGEDNYQLYLIRPASTSQSDFINLLFDRPLLLLIVTMLVSAPLLLWLAWSLAKPARKLKNAADEVAQGNLRQHPELEAGPQEFLAAGASFNQMVTALERMMTSQQRLLSDISHELRTPLTRLQLGTALLRRRSGESKELERIETEAHRLDSMINDLLVMSRNQAKNALVSETVKANQLWNEVLDNAAFEAEQMGKSFTVEYPPGPWPLYGNPNALESALENIVRNALRYSHTKISVSFSVDKDGITVNVDDDGPGVSPEDREQIFRPFYRTDEARDRESGGTGLGLAIVETAIQQHRGWVKADDSPLGGLRLTIWLPLYKRT","length":453,"molWeight":51360,"crc64":"8CAC213299969077","md5":"0818B6BF6BE10649DE8DE204A0D9D85F"},"extraAttributes":{"countByCommentType":{"FUNCTION":1,"CATALYTIC ACTIVITY":1,"ACTIVITY REGULATION":1,"SUBUNIT":1,"SUBCELLULAR LOCATION":1,"INDUCTION":1,"DISRUPTION PHENOTYPE":1},"countByFeatureType":{"Chain":1,"Topological domain":3,"Transmembrane":2,"Domain":2,"Active site":1,"Binding site":5,"Modified residue":1},"uniParcId":"UPI000241E3CD"}}