{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"C7H4X2","uniProtkbId":"MAM_FAEDU","entryAudit":{"firstPublicDate":"2021-04-07","lastAnnotationUpdateDate":"2026-11-04","lastSequenceUpdateDate":"2009-10-13","entryVersion":45,"sequenceVersion":1},"annotationScore":2.0,"organism":{"scientificName":"Faecalibacterium duncaniae","taxonId":411483,"lineage":["Bacteria","Bacillati","Bacillota","Clostridia","Eubacteriales","Oscillospiraceae","Faecalibacterium"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"26045134"}],"value":"Microbial anti-inflammatory molecule"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"26045134"}],"value":"MAM"}]}},"genes":[{"orfNames":[{"value":"FAEPRAA2165_01342"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"18936492"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26045134"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"28203226"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"31503404"}],"value":"Plays an anti-inflammatory role in the mammalian intestine. The supernatant of this bacteria, or 2 purified fractions containing peptides derived from this protein, exerts inhibitory effects on IL1-beta-induced IL-8 secretion in intestinal epithelial CaCO-2 cells (PubMed:18936492, PubMed:26045134). Mice fed this bacterium suffer less severe symptoms in 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced colitis (PubMed:18936492). Expression in human epithelial cell lines (HEK293T, HT29) shows a decrease in activation of NF-kappa-B induced by Carma-1 (CARD11) or lipopolysaccharide. The decrease occurs in a MAM-dose dependent manner. Also inhibits activation induced by IKBKB in HEK293T cells. Expression in cell lines has no effect on the STAT3 pathway. L.lactis expressing the protein offers a protective effect to mice in dinitrobenzene sulfonic acid (DNBS) and dextran sodium sulfate (DSS)-induced colitis (PubMed:26045134, PubMed:28203226). It may play a role in maintaining the intestinal barrier, which is important in diabetes mellitus (Probable)"}],"commentType":"FUNCTION"},{"commentType":"SUBCELLULAR LOCATION","note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26045134"}],"value":"Detected in cell supernatants as a mixture of peptides corresponding to residues 49-68; 50-68; 51-68; 52-68; 53-68; 69-111 and 112-135. 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In a mouse model of diabetes mellitus there is a significantly reduced population of Faecalibacterium (PubMed:31503404)"}],"commentType":"MISCELLANEOUS"}],"features":[{"type":"Chain","location":{"start":{"value":1,"modifier":"EXACT"},"end":{"value":135,"modifier":"EXACT"}},"description":"Microbial anti-inflammatory molecule","featureId":"PRO_0000452170"}],"keywords":[{"id":"KW-0903","category":"Technical term","name":"Direct protein sequencing"},{"id":"KW-1185","category":"Technical term","name":"Reference proteome"},{"id":"KW-0964","category":"Cellular component","name":"Secreted"}],"references":[{"referenceNumber":1,"citation":{"id":"CI-1G0OISKO7IBEK","citationType":"submission","authors":["Weinstock G.","Sodergren E.","Clifton S.","Fulton L.","Fulton B.","Courtney L.","Fronick C.","Harrison M.","Strong C.","Farmer C.","Delahaunty K.","Markovic C.","Hall O.","Minx P.","Tomlinson C.","Mitreva M.","Nelson J.","Hou S.","Wollam A.","Pepin K.H.","Johnson M.","Bhonagiri V.","Nash W.E.","Warren W.","Chinwalla A.","Mardis E.R.","Wilson R.K."],"publicationDate":"AUG-2009","submissionDatabase":"EMBL/GenBank/DDBJ databases"},"referencePositions":["NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]"],"referenceComments":[{"value":"DSM 17677 / JCM 31915 / A2-165","type":"STRAIN"}]},{"referenceNumber":2,"citation":{"id":"26045134","citationType":"journal article","authors":["Quevrain E.","Maubert M.A.","Michon C.","Chain F.","Marquant R.","Tailhades J.","Miquel S.","Carlier L.","Bermudez-Humaran L.G.","Pigneur B.","Lequin O.","Kharrat P.","Thomas G.","Rainteau D.","Aubry C.","Breyner N.","Afonso C.","Lavielle S.","Grill J.P.","Chassaing G.","Chatel J.M.","Trugnan G.","Xavier R.","Langella P.","Sokol H.","Seksik P."],"citationCrossReferences":[{"database":"PubMed","id":"26045134"},{"database":"DOI","id":"10.1136/gutjnl-2014-307649"}],"title":"Identification of an anti-inflammatory protein from Faecalibacterium prausnitzii, a commensal bacterium deficient in Crohn's disease.","publicationDate":"2016","journal":"Gut","firstPage":"415","lastPage":"425","volume":"65"},"referencePositions":["PROTEIN SEQUENCE OF 49-135","ANTI-INFLAMMATORY FUNCTION","IDENTIFICATION BY MASS SPECTROMETRY","SUBCELLULAR LOCATION"],"referenceComments":[{"value":"DSM 17677 / JCM 31915 / A2-165","type":"STRAIN"}]},{"referenceNumber":3,"citation":{"id":"18936492","citationType":"journal article","authors":["Sokol H.","Pigneur B.","Watterlot L.","Lakhdari O.","Bermudez-Humaran L.G.","Gratadoux J.J.","Blugeon S.","Bridonneau C.","Furet J.P.","Corthier G.","Grangette C.","Vasquez N.","Pochart P.","Trugnan G.","Thomas G.","Blottiere H.M.","Dore J.","Marteau P.","Seksik P.","Langella P."],"citationCrossReferences":[{"database":"PubMed","id":"18936492"},{"database":"DOI","id":"10.1073/pnas.0804812105"}],"title":"Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients.","publicationDate":"2008","journal":"Proc. 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CPSase catalyzes the formation of carbamoyl phosphate from the ammonia moiety of glutamine, carbonate, and phosphate donated by ATP, constituting the first step of 2 biosynthetic pathways, one leading to arginine and/or urea and the other to pyrimidine nucleotides. The large subunit (synthetase) binds the substrates ammonia (free or transferred from glutamine from the small subunit), hydrogencarbonate and ATP and carries out an ATP-coupled ligase reaction, activating hydrogencarbonate by forming carboxy phosphate which reacts with ammonia to form carbamoyl phosphate"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"hydrogencarbonate + L-glutamine + 2 ATP + H2O = carbamoyl phosphate + L-glutamate + 2 ADP + phosphate + 2 H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:18633"},{"database":"ChEBI","id":"CHEBI:15377"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:17544"},{"database":"ChEBI","id":"CHEBI:29985"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:43474"},{"database":"ChEBI","id":"CHEBI:58228"},{"database":"ChEBI","id":"CHEBI:58359"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"6.3.5.5","evidences":[{"evidenceCode":"ECO:0000256","source":"HAMAP-Rule","id":"MF_01210"}]}},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"hydrogencarbonate + NH4(+) + 2 ATP = carbamoyl phosphate + 2 ADP + phosphate + 2 H(+)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:18029"},{"database":"ChEBI","id":"CHEBI:15378"},{"database":"ChEBI","id":"CHEBI:17544"},{"database":"ChEBI","id":"CHEBI:28938"},{"database":"ChEBI","id":"CHEBI:30616"},{"database":"ChEBI","id":"CHEBI:43474"},{"database":"ChEBI","id":"CHEBI:58228"},{"database":"ChEBI","id":"CHEBI:456216"}],"ecNumber":"6.3.4.16","evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00047359"},{"evidenceCode":"ECO:0000256","source":"HAMAP-Rule","id":"MF_01210"}]}},{"commentType":"COFACTOR","cofactors":[{"name":"Mg(2+)","evidences":[{"evidenceCode":"ECO:0000256","source":"HAMAP-Rule","id":"MF_01210"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:18420"}},{"name":"Mn(2+)","evidences":[{"evidenceCode":"ECO:0000256","source":"HAMAP-Rule","id":"MF_01210"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:29035"}}],"note":{"texts":[{"evidences":[{"evidenceCode":"ECO:0000256","source":"HAMAP-Rule","id":"MF_01210"}],"value":"Binds 4 Mg(2+) or Mn(2+) ions per subunit."}]}},{"commentType":"COFACTOR","cofactors":[{"name":"Mn(2+)","evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00001936"}],"cofactorCrossReference":{"database":"ChEBI","id":"CHEBI:29035"}}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000256","source":"ARBA","id":"ARBA00005077"},{"evidenceCode":"ECO:0000256","source":"HAMAP-Rule","id":"MF_01210"}],"value":"Amino-acid biosynthesis; L-arginine biosynthesis; carbamoyl phosphate from bicarbonate: step 1/1"}],"commentType":"PATHWAY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000256","source":"HAMAP-Rule","id":"MF_01210"}],"value":"Pyrimidine metabolism; UMP biosynthesis via de novo pathway; (S)-dihydroorotate from bicarbonate: step 1/3"}],"commentType":"PATHWAY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000256","source":"HAMAP-Rule","id":"MF_01210"}],"value":"Composed of two chains; the small (or glutamine) chain promotes the hydrolysis of glutamine to ammonia, which is used by the large (or ammonia) chain to synthesize carbamoyl phosphate. 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