ID   MAM_FAEPA               Reviewed;         135 AA.
AC   C7H4X2;
DT   07-APR-2021, integrated into UniProtKB/Swiss-Prot.
DT   13-OCT-2009, sequence version 1.
DT   03-AUG-2022, entry version 31.
DE   RecName: Full=Microbial anti-inflammatory molecule {ECO:0000303|PubMed:26045134};
DE            Short=MAM {ECO:0000303|PubMed:26045134};
GN   ORFNames=FAEPRAA2165_01342;
OS   Faecalibacterium prausnitzii (strain DSM 17677 / JCM 31915 / A2-165)
OS   (Faecalibacterium duncaniae).
OC   Bacteria; Firmicutes; Clostridia; Eubacteriales; Oscillospiraceae;
OC   Faecalibacterium.
OX   NCBI_TaxID=411483;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=DSM 17677 / JCM 31915 / A2-165;
RA   Weinstock G., Sodergren E., Clifton S., Fulton L., Fulton B., Courtney L.,
RA   Fronick C., Harrison M., Strong C., Farmer C., Delahaunty K., Markovic C.,
RA   Hall O., Minx P., Tomlinson C., Mitreva M., Nelson J., Hou S., Wollam A.,
RA   Pepin K.H., Johnson M., Bhonagiri V., Nash W.E., Warren W., Chinwalla A.,
RA   Mardis E.R., Wilson R.K.;
RL   Submitted (AUG-2009) to the EMBL/GenBank/DDBJ databases.
RN   [2]
RP   PROTEIN SEQUENCE OF 49-135, ANTI-INFLAMMATORY FUNCTION, IDENTIFICATION BY
RP   MASS SPECTROMETRY, AND SUBCELLULAR LOCATION.
RC   STRAIN=DSM 17677 / JCM 31915 / A2-165;
RX   PubMed=26045134; DOI=10.1136/gutjnl-2014-307649;
RA   Quevrain E., Maubert M.A., Michon C., Chain F., Marquant R., Tailhades J.,
RA   Miquel S., Carlier L., Bermudez-Humaran L.G., Pigneur B., Lequin O.,
RA   Kharrat P., Thomas G., Rainteau D., Aubry C., Breyner N., Afonso C.,
RA   Lavielle S., Grill J.P., Chassaing G., Chatel J.M., Trugnan G., Xavier R.,
RA   Langella P., Sokol H., Seksik P.;
RT   "Identification of an anti-inflammatory protein from Faecalibacterium
RT   prausnitzii, a commensal bacterium deficient in Crohn's disease.";
RL   Gut 65:415-425(2016).
RN   [3]
RP   ANTI-INFLAMMATORY FUNCTION OF CULTURE SUPERNATANT IN CROHN DISEASE.
RX   PubMed=18936492; DOI=10.1073/pnas.0804812105;
RA   Sokol H., Pigneur B., Watterlot L., Lakhdari O., Bermudez-Humaran L.G.,
RA   Gratadoux J.J., Blugeon S., Bridonneau C., Furet J.P., Corthier G.,
RA   Grangette C., Vasquez N., Pochart P., Trugnan G., Thomas G.,
RA   Blottiere H.M., Dore J., Marteau P., Seksik P., Langella P.;
RT   "Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium
RT   identified by gut microbiota analysis of Crohn disease patients.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:16731-16736(2008).
RN   [4]
RP   ANTI-INFLAMMATORY FUNCTION.
RC   STRAIN=DSM 17677 / JCM 31915 / A2-165;
RX   PubMed=28203226; DOI=10.3389/fmicb.2017.00114;
RA   Breyner N.M., Michon C., de Sousa C.S., Vilas Boas P.B., Chain F.,
RA   Azevedo V.A., Langella P., Chatel J.M.;
RT   "Microbial Anti-Inflammatory Molecule (MAM) from Faecalibacterium
RT   prausnitzii Shows a Protective Effect on DNBS and DSS-Induced Colitis Model
RT   in Mice through Inhibition of NF-kappaB Pathway.";
RL   Front. Microbiol. 8:114-114(2017).
RN   [5]
RP   POSSIBLE FUNCTION IN DIABETES MELLITUS, AND INDUCTION.
RX   PubMed=31503404; DOI=10.1111/1753-0407.12986;
RA   Xu J., Liang R., Zhang W., Tian K., Li J., Chen X., Yu T., Chen Q.;
RT   "Faecalibacterium prausnitzii-derived microbial anti-inflammatory molecule
RT   regulates intestinal integrity in diabetes mellitus mice via modulating
RT   tight junction protein expression.";
RL   J. Diabetes 12:224-236(2020).
CC   -!- FUNCTION: Plays an anti-inflammatory role in the mammalian intestine.
CC       The supernatant of this bacteria, or 2 purified fractions containing
CC       peptides derived from this protein, exerts inhibitory effects on IL1-
CC       beta-induced IL-8 secretion in intestinal epithelial CaCO-2 cells
CC       (PubMed:18936492, PubMed:26045134). Mice fed this bacterium suffer less
CC       severe symptoms in 2,4,6-trinitrobenzenesulphonic acid (TNBS)-induced
CC       colitis (PubMed:18936492). Expression in human epithelial cell lines
CC       (HEK293T, HT29) shows a decrease in activation of NF-kappa-B induced by
CC       Carma-1 (CARD11) or lipopolysaccharide. The decrease occurs in a MAM-
CC       dose dependent manner. Also inhibits activation induced by IKBKB in
CC       HEK293T cells. Expression in cell lines has no effect on the STAT3
CC       pathway. L.lactis expressing the protein offers a protective effect to
CC       mice in dinitrobenzene sulfonic acid (DNBS) and dextran sodium sulfate
CC       (DSS)-induced colitis (PubMed:26045134, PubMed:28203226). It may play a
CC       role in maintaining the intestinal barrier, which is important in
CC       diabetes mellitus (Probable). {ECO:0000269|PubMed:18936492,
CC       ECO:0000269|PubMed:26045134, ECO:0000269|PubMed:28203226,
CC       ECO:0000305|PubMed:31503404}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:26045134}.
CC       Note=Detected in cell supernatants as a mixture of peptides
CC       corresponding to residues 49-68; 50-68; 51-68; 52-68; 53-68; 69-111 and
CC       112-135. When transfected in human cells surrounds the nucleus and
CC       colocalizes with IKBKB. {ECO:0000269|PubMed:26045134}.
CC   -!- INDUCTION: Transcribed in the gut of mice with diabetes mellitus (db/db
CC       mice). {ECO:0000269|PubMed:31503404}.
CC   -!- MISCELLANEOUS: Crohn disease is an inflammatory bowel disease. This
CC       commensal, butyrate-producing bacterium, isolated from a human fecal
CC       sample, is reduced in some patients suffering from Crohn disease
CC       (PubMed:18936492). In a mouse model of diabetes mellitus there is a
CC       significantly reduced population of Faecalibacterium (PubMed:31503404).
CC       {ECO:0000269|PubMed:18936492, ECO:0000269|PubMed:31503404}.
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DR   EMBL; ACOP02000038; EEU97043.1; -; Genomic_DNA.
DR   RefSeq; WP_005932151.1; NZ_GG697151.2.
DR   AlphaFoldDB; C7H4X2; -.
DR   STRING; 411483.FAEPRAA2165_01342; -.
DR   EnsemblBacteria; EEU97043; EEU97043; FAEPRAA2165_01342.
DR   PATRIC; fig|411483.3.peg.1355; -.
DR   HOGENOM; CLU_1803285_0_0_9; -.
DR   Proteomes; UP000004619; Unassembled WGS sequence.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
PE   1: Evidence at protein level;
KW   Direct protein sequencing; Reference proteome; Secreted.
FT   CHAIN           1..135
FT                   /note="Microbial anti-inflammatory molecule"
FT                   /id="PRO_0000452170"
SQ   SEQUENCE   135 AA;  14501 MW;  72D23B85D56CD15A CRC64;
     MMMPANYSVI AENEMTYVNG GANFIDAIGA VTAPIWTLDN VKTFNTNIVT LVGNTFLQST
     INRTIGVLFS GNTTWKEVGN IGKNLFGTNV KGNPIEKNNF GDYAMNALGI AAAVYNLGVA
     PTKNTVKETE VKFTV