FGL1_MOUSE
ID FGL1_MOUSE Reviewed; 314 AA.
AC Q71KU9; Q8VC25;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 18-MAR-2008, sequence version 2.
DT 25-MAY-2022, entry version 108.
DE RecName: Full=Fibrinogen-like protein 1;
DE AltName: Full=Fibrinogen-related protein 1 {ECO:0000303|PubMed:12528893};
DE Short=Mfrep-1 {ECO:0000303|PubMed:12528893};
DE AltName: Full=Liver fibrinogen-related protein-1 {ECO:0000303|PubMed:12528893};
DE Short=Mfire-1 {ECO:0000303|PubMed:12528893};
DE Flags: Precursor;
GN Name=Fgl1; Synonyms=Mfire1 {ECO:0000303|PubMed:12528893};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Liver;
RX PubMed=12528893; DOI=10.1038/sj.cr.7290137;
RA Yan J., Ying H., Gu F., He J., Li Y.L., Liu H.M., Xu Y.H.;
RT "Cloning and characterization of a mouse liver-specific gene mfrep-1, up-
RT regulated in liver regeneration.";
RL Cell Res. 12:353-361(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [4]
RP DISRUPTION PHENOTYPE, AND TISSUE SPECIFICITY.
RX PubMed=23483972; DOI=10.1371/journal.pone.0058084;
RA Demchev V., Malana G., Vangala D., Stoll J., Desai A., Kang H.W., Li Y.,
RA Nayeb-Hashemi H., Niepel M., Cohen D.E., Ukomadu C.;
RT "Targeted deletion of fibrinogen like protein 1 reveals a novel role in
RT energy substrate utilization.";
RL PLoS ONE 8:E58084-E58084(2013).
RN [5]
RP FUNCTION, INTERACTION WITH LAG3, SUBCELLULAR LOCATION, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=30580966; DOI=10.1016/j.cell.2018.11.010;
RA Wang J., Sanmamed M.F., Datar I., Su T.T., Ji L., Sun J., Chen L., Chen Y.,
RA Zhu G., Yin W., Zheng L., Zhou T., Badri T., Yao S., Zhu S., Boto A.,
RA Sznol M., Melero I., Vignali D.A.A., Schalper K., Chen L.;
RT "Fibrinogen-like protein 1 is a major immune inhibitory ligand of LAG-3.";
RL Cell 0:0-0(2018).
CC -!- FUNCTION: Immune suppressive molecule that inhibits antigen-specific T-
CC cell activation by acting as a major ligand of LAG3 (PubMed:30580966).
CC Responsible for LAG3 T-cell inhibitory function (PubMed:30580966).
CC Binds LAG3 independently from MHC class II (MHC-II) (PubMed:30580966).
CC Secreted by, and promotes growth of, hepatocytes (By similarity).
CC {ECO:0000250|UniProtKB:Q08830, ECO:0000269|PubMed:30580966}.
CC -!- SUBUNIT: Homodimer (By similarity). Interacts (via the Fibrinogen C-
CC terminal domain) with LAG3 (via Ig-like domains 1 and 2)
CC (PubMed:30580966). {ECO:0000250|UniProtKB:Q08830,
CC ECO:0000269|PubMed:30580966}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:30580966}.
CC Note=Secreted in the blood plasma. {ECO:0000269|PubMed:30580966}.
CC -!- TISSUE SPECIFICITY: Mainly expressed in liver (PubMed:12528893,
CC PubMed:23483972). Also expressed in brown adipose tissue
CC (PubMed:23483972). {ECO:0000269|PubMed:12528893,
CC ECO:0000269|PubMed:23483972}.
CC -!- DISRUPTION PHENOTYPE: Mice develop normally but develop spontaneous
CC autoimmune symptoms caused by T-cell activation in aged mice
CC (PubMed:30580966). Mice also display slight metabolic defects: mice are
CC heavier than wild type mates, have abnormal plasma lipid profiles,
CC fasting hyperglycemia with enhanced gluconeogenesis and exhibit
CC differences in white and brown adipose tissue morphology
CC (PubMed:23483972). {ECO:0000269|PubMed:23483972,
CC ECO:0000269|PubMed:30580966}.
CC -!- MISCELLANEOUS: Blockade of the FGL1-LAG-3 interaction using a
CC monoclonal antibody stimulates tumor immunity and is therapeutic
CC against established mouse tumors in a receptor-ligand interdependent
CC manner. {ECO:0000269|PubMed:30580966}.
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DR EMBL; AF478470; AAQ05798.1; -; mRNA.
DR EMBL; BC021946; AAH21946.1; -; mRNA.
DR CCDS; CCDS22260.1; -.
DR RefSeq; NP_663569.2; NM_145594.2.
DR RefSeq; XP_011240489.1; XM_011242187.1.
DR AlphaFoldDB; Q71KU9; -.
DR SMR; Q71KU9; -.
DR STRING; 10090.ENSMUSP00000034003; -.
DR iPTMnet; Q71KU9; -.
DR PhosphoSitePlus; Q71KU9; -.
DR CPTAC; non-CPTAC-3708; -.
DR MaxQB; Q71KU9; -.
DR PaxDb; Q71KU9; -.
DR PRIDE; Q71KU9; -.
DR ProteomicsDB; 266840; -.
DR DNASU; 234199; -.
DR GeneID; 234199; -.
DR KEGG; mmu:234199; -.
DR UCSC; uc009lnp.2; mouse.
DR CTD; 2267; -.
DR MGI; MGI:102795; Fgl1.
DR eggNOG; KOG2579; Eukaryota.
DR InParanoid; Q71KU9; -.
DR OrthoDB; 523014at2759; -.
DR PhylomeDB; Q71KU9; -.
DR TreeFam; TF336658; -.
DR BioGRID-ORCS; 234199; 3 hits in 73 CRISPR screens.
DR ChiTaRS; Fgl1; mouse.
DR PRO; PR:Q71KU9; -.
DR Proteomes; UP000000589; Unplaced.
DR RNAct; Q71KU9; protein.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005102; F:signaling receptor binding; IBA:GO_Central.
DR GO; GO:0002250; P:adaptive immune response; IEA:UniProtKB-KW.
DR GO; GO:0060612; P:adipose tissue development; IMP:MGI.
DR GO; GO:0008203; P:cholesterol metabolic process; IMP:MGI.
DR GO; GO:0072574; P:hepatocyte proliferation; ISS:UniProtKB.
DR GO; GO:0050868; P:negative regulation of T cell activation; IDA:UniProtKB.
DR GO; GO:0010906; P:regulation of glucose metabolic process; IMP:MGI.
DR GO; GO:0050776; P:regulation of immune response; IDA:UniProtKB.
DR GO; GO:0035634; P:response to stilbenoid; IEP:UniProtKB.
DR CDD; cd00087; FReD; 1.
DR Gene3D; 3.90.215.10; -; 1.
DR InterPro; IPR036056; Fibrinogen-like_C.
DR InterPro; IPR014716; Fibrinogen_a/b/g_C_1.
DR InterPro; IPR002181; Fibrinogen_a/b/g_C_dom.
DR InterPro; IPR020837; Fibrinogen_CS.
DR Pfam; PF00147; Fibrinogen_C; 1.
DR SMART; SM00186; FBG; 1.
DR SUPFAM; SSF56496; SSF56496; 1.
DR PROSITE; PS00514; FIBRINOGEN_C_1; 1.
DR PROSITE; PS51406; FIBRINOGEN_C_2; 1.
PE 1: Evidence at protein level;
KW Adaptive immunity; Coiled coil; Disulfide bond; Immunity;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000250|UniProtKB:Q08830"
FT CHAIN 23..314
FT /note="Fibrinogen-like protein 1"
FT /id="PRO_0000322979"
FT DOMAIN 76..308
FT /note="Fibrinogen C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT COILED 28..62
FT /evidence="ECO:0000255"
FT DISULFID 28
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT DISULFID 85..114
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT DISULFID 250..263
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT CONFLICT 27
FT /note="S -> N (in Ref. 1; AAQ05798)"
FT /evidence="ECO:0000305"
FT CONFLICT 80
FT /note="R -> K (in Ref. 1; AAQ05798)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 314 AA; 36439 MW; 52C16CA9C2D0386A CRC64;
MGKIYSFVLV AIALMMGREG WALESESCLR EQVRLRAQVH QLETRVKQQQ TMIAQLLHEK
EVQFLDKGSE NSFIDLGGKR QYADCSEIYN DGFKQSGFYK IKPLQSLAEF SVYCDMSDGG
GWTVIQRRSD GSENFNRGWN DYENGFGNFV QNNGEYWLGN KNINLLTIQG DYTLKIDLTD
FEKNSSFAQY QSFKVGDKKS FYELNIGEYS GTAGDSLSGT FHPEVQWWAS HQRMKFSTWD
RDNDNYQGNC AEEEQSGWWF NRCHSANLNG VYYRGSYRAE TDNGVVWYTW HGWWYSLKSV
VMKIRPSDFI PNII
