{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P06989","secondaryAccessions":["P78079","Q47596"],"uniProtkbId":"HIS2_ECOLI","entryAudit":{"firstPublicDate":"1988-04-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"1995-02-01","entryVersion":188,"sequenceVersion":3},"annotationScore":4.0,"organism":{"scientificName":"Escherichia coli (strain K12)","taxonId":83333,"lineage":["Bacteria","Pseudomonadati","Pseudomonadota","Gammaproteobacteria","Enterobacterales","Enterobacteriaceae","Escherichia"]},"proteinExistence":"3: Inferred from homology","proteinDescription":{"recommendedName":{"fullName":{"value":"Histidine biosynthesis bifunctional protein HisIE"}},"includes":[{"recommendedName":{"fullName":{"value":"Phosphoribosyl-AMP cyclohydrolase"},"shortNames":[{"value":"PRA-CH"}],"ecNumbers":[{"value":"3.5.4.19"}]}},{"recommendedName":{"fullName":{"value":"Phosphoribosyl-ATP pyrophosphatase"},"shortNames":[{"value":"PRA-PH"}],"ecNumbers":[{"value":"3.6.1.31"}]}}]},"genes":[{"geneName":{"value":"hisI"},"synonyms":[{"value":"hisIE"}],"orderedLocusNames":[{"value":"b2026"},{"value":"JW2008"}]}],"comments":[{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"1-(5-phospho-beta-D-ribosyl)-ATP + H2O = 1-(5-phospho-beta-D-ribosyl)-5'-AMP + diphosphate + H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:22828"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:33019"},{"database":"ChEBI","id":"CHEBI:59457"},{"database":"ChEBI","id":"CHEBI:73183"}],"ecNumber":"3.6.1.31"}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"1-(5-phospho-beta-D-ribosyl)-5'-AMP + H2O = 1-(5-phospho-beta-D-ribosyl)-5-[(5-phospho-beta-D-ribosylamino)methylideneamino]imidazole-4-carboxamide","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:20049"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:58435"},{"database":"ChEBI","id":"CHEBI:59457"}],"ecNumber":"3.5.4.19"}},{"texts":[{"value":"Amino-acid biosynthesis; L-histidine biosynthesis; L-histidine from 5-phospho-alpha-D-ribose 1-diphosphate: step 2/9"}],"commentType":"PATHWAY"},{"texts":[{"value":"Amino-acid biosynthesis; L-histidine biosynthesis; L-histidine from 5-phospho-alpha-D-ribose 1-diphosphate: step 3/9"}],"commentType":"PATHWAY"},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"value":"Cytoplasm","id":"SL-0086"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"In the N-terminal section; belongs to the PRA-CH family"}],"commentType":"SIMILARITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"In the C-terminal section; belongs to the PRA-PH family"}],"commentType":"SIMILARITY"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":203,"modifier":"EXACT"}},"description":"Histidine biosynthesis bifunctional protein HisIE","featureId":"PRO_0000136411"},{"type":"Region","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":114,"modifier":"EXACT"}},"description":"Phosphoribosyl-AMP cyclohydrolase"},{"type":"Region","location":{"start":{"value":115,"modifier":"EXACT"},"end":{"value":203,"modifier":"EXACT"}},"description":"Phosphoribosyl-ATP pyrophosphohydrolase"},{"type":"Natural variant","location":{"start":{"value":5,"modifier":"EXACT"},"end":{"value":5,"modifier":"EXACT"}},"description":"in strain: F719","featureId":"","alternativeSequence":{"originalSequence":"Q","alternativeSequences":["L"]}},{"type":"Natural variant","location":{"start":{"value":46,"modifier":"EXACT"},"end":{"value":46,"modifier":"EXACT"}},"description":"in strain: F719","featureId":"","alternativeSequence":{"originalSequence":"L","alternativeSequences":["I"]}},{"type":"Natural variant","location":{"start":{"value":164,"modifier":"EXACT"},"end":{"value":164,"modifier":"EXACT"}},"description":"in strain: F719","featureId":"","alternativeSequence":{"originalSequence":"H","alternativeSequences":["N"]}},{"type":"Natural variant","location":{"start":{"value":192,"modifier":"EXACT"},"end":{"value":193,"modifier":"EXACT"}},"description":"in strain: F719","featureId":"","alternativeSequence":{"originalSequence":"TT","alternativeSequences":["GE"]}},{"type":"Natural variant","location":{"start":{"value":196,"modifier":"EXACT"},"end":{"value":196,"modifier":"EXACT"}},"description":"in strain: F719","featureId":"","alternativeSequence":{"originalSequence":"E","alternativeSequences":["D"]}},{"type":"Natural variant","location":{"start":{"value":199,"modifier":"EXACT"},"end":{"value":200,"modifier":"EXACT"}},"description":"in strain: F719","featureId":"","alternativeSequence":{"originalSequence":"RK","alternativeSequences":["KN"]}},{"type":"Natural variant","location":{"start":{"value":203,"modifier":"EXACT"},"end":{"value":203,"modifier":"EXACT"}},"description":"in strain: F719","featureId":"","alternativeSequence":{}},{"type":"Sequence conflict","location":{"start":{"value":68,"modifier":"EXACT"},"end":{"value":68,"modifier":"EXACT"}},"description":"in Ref. 1; CAA31818","evidences":[{"evidenceCode":"ECO:0000305"}],"alternativeSequence":{"originalSequence":"S","alternativeSequences":["P"]}},{"type":"Sequence conflict","location":{"start":{"value":193,"modifier":"EXACT"},"end":{"value":193,"modifier":"EXACT"}},"description":"in Ref. 1 and 2","evidences":[{"evidenceCode":"ECO:0000305"}],"alternativeSequence":{"originalSequence":"T","alternativeSequences":["P"]}}],"keywords":[{"id":"KW-0028","category":"Biological process","name":"Amino-acid biosynthesis"},{"id":"KW-0067","category":"Ligand","name":"ATP-binding"},{"id":"KW-0963","category":"Cellular component","name":"Cytoplasm"},{"id":"KW-0368","category":"Biological process","name":"Histidine biosynthesis"},{"id":"KW-0378","category":"Molecular function","name":"Hydrolase"},{"id":"KW-0511","category":"Molecular function","name":"Multifunctional enzyme"},{"id":"KW-0547","category":"Ligand","name":"Nucleotide-binding"},{"id":"KW-1185","category":"Technical term","name":"Reference proteome"}],"references":[{"referenceNumber":1,"citation":{"id":"3062174","citationType":"journal article","authors":["Carlomagno M.S.","Chiariotti L.","Alifano P.","Nappo A.G.","Bruni C.B."],"citationCrossReferences":[{"database":"PubMed","id":"3062174"},{"database":"DOI","id":"10.1016/0022-2836(88)90194-5"}],"title":"Structure and function of the Salmonella typhimurium and Escherichia coli K-12 histidine operons.","publicationDate":"1988","journal":"J. Mol. Biol.","firstPage":"585","lastPage":"606","volume":"203"},"referencePositions":["NUCLEOTIDE SEQUENCE [GENOMIC DNA]"],"referenceComments":[{"value":"K12","type":"STRAIN"}]},{"referenceNumber":2,"citation":{"id":"3018428","citationType":"journal article","authors":["Chiariotti L.","Alifano P.","Carlomagno M.S.","Bruni C.B."],"citationCrossReferences":[{"database":"PubMed","id":"3018428"},{"database":"DOI","id":"10.1007/bf00422061"}],"title":"Nucleotide sequence of the Escherichia coli hisD gene and of the Escherichia coli and Salmonella typhimurium hisIE region.","publicationDate":"1986","journal":"Mol. Gen. Genet.","firstPage":"382","lastPage":"388","volume":"203"},"referencePositions":["NUCLEOTIDE SEQUENCE [GENOMIC DNA]"]},{"referenceNumber":3,"citation":{"id":"8201624","citationType":"journal article","authors":["Jovanovic G.","Kostic T.","Jankovic M.","Savic D.J."],"citationCrossReferences":[{"database":"PubMed","id":"8201624"},{"database":"DOI","id":"10.1006/jmbi.1994.1384"}],"title":"Nucleotide sequence of the Escherichia coli K12 histidine operon revisited.","publicationDate":"1994","journal":"J. Mol. Biol.","firstPage":"433","lastPage":"435","volume":"239"},"referencePositions":["NUCLEOTIDE SEQUENCE [GENOMIC DNA]","SEQUENCE REVISION"],"referenceComments":[{"value":"K12","type":"STRAIN"}]},{"referenceNumber":4,"citation":{"id":"7536735","citationType":"journal article","authors":["Kido N.","Torgov V.I.","Sugiyama T.","Uchiya K.","Sugihara H.","Komatsu T.","Kato N.","Jann K."],"citationCrossReferences":[{"database":"PubMed","id":"7536735"},{"database":"DOI","id":"10.1128/jb.177.8.2178-2187.1995"}],"title":"Expression of the O9 polysaccharide of Escherichia coli: sequencing of the E. coli O9 rfb gene cluster, characterization of mannosyl transferases, and evidence for an ATP-binding cassette transport system.","publicationDate":"1995","journal":"J. Bacteriol.","firstPage":"2178","lastPage":"2187","volume":"177"},"referencePositions":["NUCLEOTIDE SEQUENCE [GENOMIC DNA]"],"referenceComments":[{"value":"O9:K31-:H- / F719","type":"STRAIN"}]},{"referenceNumber":5,"citation":{"id":"9097040","citationType":"journal article","authors":["Itoh T.","Aiba H.","Baba T.","Fujita K.","Hayashi K.","Inada T.","Isono K.","Kasai H.","Kimura S.","Kitakawa M.","Kitagawa M.","Makino K.","Miki T.","Mizobuchi K.","Mori H.","Mori T.","Motomura K.","Nakade S.","Nakamura Y.","Nashimoto H.","Nishio Y.","Oshima T.","Saito N.","Sampei G.","Seki Y.","Sivasundaram S.","Tagami H.","Takeda J.","Takemoto K.","Wada C.","Yamamoto Y.","Horiuchi T."],"citationCrossReferences":[{"database":"PubMed","id":"9097040"},{"database":"DOI","id":"10.1093/dnares/3.6.379"}],"title":"A 460-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 40.1-50.0 min region on the linkage map.","publicationDate":"1996","journal":"DNA Res.","firstPage":"379","lastPage":"392","volume":"3"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"referenceComments":[{"value":"K12 / W3110 / ATCC 27325 / DSM 5911","type":"STRAIN"}]},{"referenceNumber":6,"citation":{"id":"9278503","citationType":"journal article","authors":["Blattner F.R.","Plunkett G. III","Bloch C.A.","Perna N.T.","Burland V.","Riley M.","Collado-Vides J.","Glasner J.D.","Rode C.K.","Mayhew G.F.","Gregor J.","Davis N.W.","Kirkpatrick H.A.","Goeden M.A.","Rose D.J.","Mau B.","Shao Y."],"citationCrossReferences":[{"database":"PubMed","id":"9278503"},{"database":"DOI","id":"10.1126/science.277.5331.1453"}],"title":"The complete genome sequence of Escherichia coli K-12.","publicationDate":"1997","journal":"Science","firstPage":"1453","lastPage":"1462","volume":"277"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"referenceComments":[{"value":"K12 / MG1655 / ATCC 47076","type":"STRAIN"}]},{"referenceNumber":7,"citation":{"id":"16738553","citationType":"journal article","authors":["Hayashi K.","Morooka N.","Yamamoto Y.","Fujita K.","Isono K.","Choi S.","Ohtsubo E.","Baba T.","Wanner B.L.","Mori H.","Horiuchi T."],"citationCrossReferences":[{"database":"PubMed","id":"16738553"},{"database":"DOI","id":"10.1038/msb4100049"}],"title":"Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110.","publicationDate":"2006","journal":"Mol. Syst. Biol.","firstPage":"E1","lastPage":"E5","volume":"2"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"referenceComments":[{"value":"K12 / W3110 / ATCC 27325 / DSM 5911","type":"STRAIN"}]}],"uniProtKBCrossReferences":[{"database":"EMBL","id":"X13462","properties":[{"key":"ProteinId","value":"CAA31818.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"EMBL","id":"X03974","properties":[{"key":"ProteinId","value":"CAA27613.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"EMBL","id":"U02072","properties":[{"key":"ProteinId","value":"AAA19744.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"Unassigned_DNA"}]},{"database":"EMBL","id":"D43637","properties":[{"key":"ProteinId","value":"BAA07753.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"EMBL","id":"U00096","properties":[{"key":"ProteinId","value":"AAC75087.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"EMBL","id":"AP009048","properties":[{"key":"ProteinId","value":"BAA15858.1"},{"key":"Status","value":"-"},{"key":"MoleculeType","value":"Genomic_DNA"}]},{"database":"PIR","id":"JS0135","properties":[{"key":"EntryName","value":"YNECHI"}]},{"database":"RefSeq","id":"NP_416530.1","properties":[{"key":"NucleotideSequenceId","value":"NC_000913.3"}]},{"database":"RefSeq","id":"WP_000954911.1","properties":[{"key":"NucleotideSequenceId","value":"NZ_CP009789.1"}]},{"database":"AlphaFoldDB","id":"P06989","properties":[{"key":"Description","value":"-"}]},{"database":"SMR","id":"P06989","properties":[{"key":"Description","value":"-"}]},{"database":"BioGRID","id":"4260421","properties":[{"key":"Interactions","value":"36"}]},{"database":"DIP","id":"DIP-9907N","properties":[{"key":"Description","value":"-"}]},{"database":"FunCoup","id":"P06989","properties":[{"key":"Number of interactors","value":"378"}]},{"database":"IntAct","id":"P06989","properties":[{"key":"Interactions","value":"15"}]},{"database":"STRING","id":"511145.b2026","properties":[{"key":"Description","value":"-"}]},{"database":"jPOST","id":"P06989","properties":[{"key":"Description","value":"-"}]},{"database":"PaxDb","id":"511145-b2026","properties":[{"key":"Description","value":"-"}]},{"database":"EnsemblBacteria","id":"AAC75087","properties":[{"key":"ProteinId","value":"AAC75087"},{"key":"GeneId","value":"b2026"}]},{"database":"GeneID","id":"946515","properties":[{"key":"Description","value":"-"}]},{"database":"KEGG","id":"ecj:JW2008","properties":[{"key":"Description","value":"-"}]},{"database":"KEGG","id":"eco:b2026","properties":[{"key":"Description","value":"-"}]},{"database":"KEGG","id":"ecoc:C3026_11420","properties":[{"key":"Description","value":"-"}]},{"database":"PATRIC","id":"fig|1411691.4.peg.226","properties":[{"key":"GeneDesignation","value":"-"}]},{"database":"EchoBASE","id":"EB0446","properties":[{"key":"Description","value":"-"}]},{"database":"eggNOG","id":"COG0139","properties":[{"key":"ToxonomicScope","value":"Bacteria"}]},{"database":"eggNOG","id":"COG0140","properties":[{"key":"ToxonomicScope","value":"Bacteria"}]},{"database":"HOGENOM","id":"CLU_048577_3_1_6","properties":[{"key":"Description","value":"-"}]},{"database":"InParanoid","id":"P06989","properties":[{"key":"Description","value":"-"}]},{"database":"OMA","id":"ERSCFHQ","properties":[{"key":"Fingerprint","value":"-"}]},{"database":"OrthoDB","id":"9795769at2","properties":[{"key":"Description","value":"-"}]},{"database":"PhylomeDB","id":"P06989","properties":[{"key":"Description","value":"-"}]},{"database":"BioCyc","id":"EcoCyc:HISTCYCLOPRATPPHOS","properties":[{"key":"Description","value":"-"}]},{"database":"BioCyc","id":"MetaCyc:HISTCYCLOPRATPPHOS","properties":[{"key":"Description","value":"-"}]},{"database":"UniPathway","id":"UPA00031","properties":[{"key":"RectionId","value":"UER00007"}]},{"database":"UniPathway","id":"UPA00031","properties":[{"key":"RectionId","value":"UER00008"}]},{"database":"PRO","id":"PR:P06989","properties":[{"key":"Description","value":"-"}]},{"database":"Proteomes","id":"UP000000625","properties":[{"key":"Component","value":"Chromosome"}]},{"database":"AbasyAtlas","id":"P06989","properties":[{"key":"Description","value":"-"}]},{"database":"GO","id":"GO:0005829","properties":[{"key":"GoTerm","value":"C:cytosol"},{"key":"GoEvidenceType","value":"IDA:EcoCyc"}],"evidences":[{"evidenceCode":"ECO:0000314","source":"PubMed","id":"15911532"}]},{"database":"GO","id":"GO:0004635","properties":[{"key":"GoTerm","value":"F:phosphoribosyl-AMP cyclohydrolase activity"},{"key":"GoEvidenceType","value":"ISS:EcoCyc"}],"evidences":[{"evidenceCode":"ECO:0000250","source":"PubMed","id":"3018428"}]},{"database":"GO","id":"GO:0004636","properties":[{"key":"GoTerm","value":"F:phosphoribosyl-ATP diphosphatase activity"},{"key":"GoEvidenceType","value":"IGI:EcoCyc"}],"evidences":[{"evidenceCode":"ECO:0000316","source":"PubMed","id":"7037745"}]},{"database":"GO","id":"GO:0000105","properties":[{"key":"GoTerm","value":"P:L-histidine biosynthetic process"},{"key":"GoEvidenceType","value":"IMP:EcoCyc"}],"evidences":[{"evidenceCode":"ECO:0000315","source":"PubMed","id":"9733547"}]},{"database":"CDD","id":"cd11534","properties":[{"key":"EntryName","value":"NTP-PPase_HisIE_like"},{"key":"MatchStatus","value":"1"}]},{"database":"FunFam","id":"1.10.287.1080:FF:000002","properties":[{"key":"EntryName","value":"Histidine biosynthesis bifunctional protein HisIE"},{"key":"MatchStatus","value":"1"}]},{"database":"FunFam","id":"3.10.20.810:FF:000001","properties":[{"key":"EntryName","value":"Histidine biosynthesis bifunctional protein HisIE"},{"key":"MatchStatus","value":"1"}]},{"database":"Gene3D","id":"1.10.287.1080","properties":[{"key":"EntryName","value":"MazG-like"},{"key":"MatchStatus","value":"1"}]},{"database":"Gene3D","id":"3.10.20.810","properties":[{"key":"EntryName","value":"Phosphoribosyl-AMP cyclohydrolase"},{"key":"MatchStatus","value":"1"}]},{"database":"HAMAP","id":"MF_01020","properties":[{"key":"EntryName","value":"HisE"},{"key":"MatchStatus","value":"1"}]},{"database":"HAMAP","id":"MF_01019","properties":[{"key":"EntryName","value":"HisIE"},{"key":"MatchStatus","value":"1"}]},{"database":"InterPro","id":"IPR023019","properties":[{"key":"EntryName","value":"His_synth_HisIE"}]},{"database":"InterPro","id":"IPR008179","properties":[{"key":"EntryName","value":"HisE"}]},{"database":"InterPro","id":"IPR021130","properties":[{"key":"EntryName","value":"PRib-ATP_PPHydrolase-like"}]},{"database":"InterPro","id":"IPR002496","properties":[{"key":"EntryName","value":"PRib_AMP_CycHydrolase_dom"}]},{"database":"InterPro","id":"IPR038019","properties":[{"key":"EntryName","value":"PRib_AMP_CycHydrolase_sf"}]},{"database":"NCBIfam","id":"TIGR03188","properties":[{"key":"EntryName","value":"histidine_hisI"},{"key":"MatchStatus","value":"1"}]},{"database":"NCBIfam","id":"NF000768","properties":[{"key":"EntryName","value":"PRK00051.1"},{"key":"MatchStatus","value":"1"}]},{"database":"NCBIfam","id":"NF002747","properties":[{"key":"EntryName","value":"PRK02759.1"},{"key":"MatchStatus","value":"1"}]},{"database":"PANTHER","id":"PTHR42945","properties":[{"key":"EntryName","value":"HISTIDINE BIOSYNTHESIS BIFUNCTIONAL PROTEIN"},{"key":"MatchStatus","value":"1"}]},{"database":"PANTHER","id":"PTHR42945:SF9","properties":[{"key":"EntryName","value":"HISTIDINE BIOSYNTHESIS BIFUNCTIONAL PROTEIN HISIE"},{"key":"MatchStatus","value":"1"}]},{"database":"Pfam","id":"PF01502","properties":[{"key":"EntryName","value":"PRA-CH"},{"key":"MatchStatus","value":"1"}]},{"database":"Pfam","id":"PF01503","properties":[{"key":"EntryName","value":"PRA-PH"},{"key":"MatchStatus","value":"1"}]},{"database":"SUPFAM","id":"SSF101386","properties":[{"key":"EntryName","value":"all-alpha NTP pyrophosphatases"},{"key":"MatchStatus","value":"1"}]},{"database":"SUPFAM","id":"SSF141734","properties":[{"key":"EntryName","value":"HisI-like"},{"key":"MatchStatus","value":"1"}]}],"sequence":{"value":"MLTEQQRRELDWEKTDGLMPVIVQHAVSGEVLMLGYMNPEALDKTLESGKVTFFSRTKQRLWTKGETSGNFLNVVSIAPDCDNDTLLVLANPIGPTCHKGTSSCFGDTAHQWLFLYQLEQLLAERKSADPETSYTAKLYASGTKRIAQKVGEEGVETALAATVHDRFELTNEASDLMYHLLVLLQDQGLDLTTVIENLRKRHQ","length":203,"molWeight":22756,"crc64":"34019009D82E0122","md5":"7A1D64718ED2CF5DAB23FC388BFB47A9"},"extraAttributes":{"countByCommentType":{"CATALYTIC ACTIVITY":2,"PATHWAY":2,"SUBCELLULAR LOCATION":1,"SIMILARITY":2},"countByFeatureType":{"Chain":1,"Region":2,"Natural variant":7,"Sequence conflict":2},"uniParcId":"UPI000012C773"}}