FGL1_HUMAN
ID FGL1_HUMAN Reviewed; 312 AA.
AC Q08830; A6NKU4; Q4PJH9; Q53YF1; Q8NG32; Q96KW6; Q96QM6;
DT 23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 15-MAY-2007, sequence version 3.
DT 03-AUG-2022, entry version 172.
DE RecName: Full=Fibrinogen-like protein 1 {ECO:0000303|PubMed:18039467};
DE AltName: Full=HP-041 {ECO:0000303|PubMed:11470158};
DE AltName: Full=Hepassocin {ECO:0000303|PubMed:11470158};
DE Short=HPS {ECO:0000303|PubMed:19880967};
DE AltName: Full=Hepatocyte-derived fibrinogen-related protein 1 {ECO:0000303|PubMed:8390249};
DE Short=HFREP-1 {ECO:0000303|PubMed:8390249};
DE AltName: Full=Liver fibrinogen-related protein 1 {ECO:0000303|Ref.3};
DE Short=LFIRE-1 {ECO:0000303|Ref.3};
DE Flags: Precursor;
GN Name=FGL1 {ECO:0000303|PubMed:18039467, ECO:0000312|HGNC:HGNC:3695};
GN Synonyms=HFREP1 {ECO:0000303|PubMed:8390249};
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS ILE-15 AND VAL-72.
RC TISSUE=Liver;
RX PubMed=8390249; DOI=10.1006/bbrc.1993.1678;
RA Yamamoto T., Gotoh M., Sasaki H., Terada M., Kitajima M., Hirohashi S.;
RT "Molecular cloning and initial characterization of a novel fibrinogen-
RT related gene, HFREP-1.";
RL Biochem. Biophys. Res. Commun. 193:681-687(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, FUNCTION, SUBCELLULAR
RP LOCATION, SUBUNIT, AND VARIANTS ILE-15 AND LEU-105.
RC TISSUE=Liver;
RX PubMed=11470158; DOI=10.1016/s0167-4781(01)00249-4;
RA Hara H., Yoshimura H., Uchida S., Toyoda Y., Aoki M., Sakai Y.,
RA Morimoto S., Shiokawa K.;
RT "Molecular cloning and functional expression analysis of a cDNA for human
RT hepassocin, a liver-specific protein with hepatocyte mitogenic activity.";
RL Biochim. Biophys. Acta 1520:45-53(2001).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS ILE-15 AND VAL-72.
RC TISSUE=Liver;
RA Yan J., Yu Y., Wang N., Xu Y.;
RT "LFIRE-1, a liver-specific expressing gene on human chromosome 8p22, is
RT frequently dowm-regulated and functions as tumor suppressor in human
RT hepatocellular carcinoma.";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS ILE-15 AND VAL-72.
RC TISSUE=Urinary bladder;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ILE-15; VAL-72; LEU-105;
RP HIS-111; SER-121 AND PHE-140.
RG SeattleSNPs variation discovery resource;
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC 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 [9]
RP INDUCTION.
RX PubMed=18039467; DOI=10.1016/j.bbrc.2007.11.069;
RA Liu Z., Ukomadu C.;
RT "Fibrinogen-like protein 1, a hepatocyte derived protein is an acute phase
RT reactant.";
RL Biochem. Biophys. Res. Commun. 365:729-734(2008).
RN [10]
RP FUNCTION.
RX PubMed=19880967; DOI=10.1136/gut.2008.171124;
RA Li C.Y., Cao C.Z., Xu W.X., Cao M.M., Yang F., Dong L., Yu M., Zhan Y.Q.,
RA Gao Y.B., Li W., Wang Z.D., Ge C.H., Wang Q.M., Peng R.Y., Yang X.M.;
RT "Recombinant human hepassocin stimulates proliferation of hepatocytes in
RT vivo and improves survival in rats with fulminant hepatic failure.";
RL Gut 59:817-826(2010).
RN [11]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [12]
RP FUNCTION, INTERACTION WITH LAG3, SUBCELLULAR LOCATION, AND INDUCTION.
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 (PubMed:11470158,
CC PubMed:19880967). {ECO:0000269|PubMed:11470158,
CC ECO:0000269|PubMed:19880967, ECO:0000269|PubMed:30580966}.
CC -!- SUBUNIT: Homodimer (PubMed:11470158). Interacts (via the Fibrinogen C-
CC terminal domain) with LAG3 (via Ig-like domains 1 and 2)
CC (PubMed:30580966). {ECO:0000269|PubMed:11470158,
CC ECO:0000269|PubMed:30580966}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11470158,
CC ECO:0000269|PubMed:30580966}. Note=Secreted in the blood plasma.
CC {ECO:0000269|PubMed:30580966}.
CC -!- TISSUE SPECIFICITY: Under normal conditions, liver-specific.
CC {ECO:0000269|PubMed:11470158}.
CC -!- INDUCTION: Expression is induced by interleukin-6 (IL6)
CC (PubMed:18039467). Up-regulated in a number of cancers, such as lung
CC cancer, prostate cancer, melanoma and colorectal cancer
CC (PubMed:30580966). {ECO:0000269|PubMed:18039467,
CC ECO:0000269|PubMed:30580966}.
CC -!- WEB RESOURCE: Name=SeattleSNPs;
CC URL="http://pga.gs.washington.edu/data/fgl1/";
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DR EMBL; D14446; BAA03336.1; -; mRNA.
DR EMBL; D87342; BAB70690.1; -; mRNA.
DR EMBL; AF168954; AAM88911.1; -; mRNA.
DR EMBL; BT006635; AAP35281.1; -; mRNA.
DR EMBL; DQ086826; AAY68216.1; -; Genomic_DNA.
DR EMBL; AK289448; BAF82137.1; -; mRNA.
DR EMBL; AC087273; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC007047; AAH07047.1; -; mRNA.
DR CCDS; CCDS6004.1; -.
DR PIR; JN0596; JN0596.
DR RefSeq; NP_004458.3; NM_004467.3.
DR RefSeq; NP_671736.2; NM_147203.2.
DR RefSeq; NP_963846.1; NM_201552.1.
DR RefSeq; NP_963847.1; NM_201553.1.
DR RefSeq; XP_016868721.1; XM_017013232.1.
DR AlphaFoldDB; Q08830; -.
DR SMR; Q08830; -.
DR BioGRID; 108558; 74.
DR IntAct; Q08830; 62.
DR STRING; 9606.ENSP00000381133; -.
DR iPTMnet; Q08830; -.
DR PhosphoSitePlus; Q08830; -.
DR BioMuta; FGL1; -.
DR DMDM; 147744562; -.
DR EPD; Q08830; -.
DR MassIVE; Q08830; -.
DR MaxQB; Q08830; -.
DR PaxDb; Q08830; -.
DR PeptideAtlas; Q08830; -.
DR PRIDE; Q08830; -.
DR ProteomicsDB; 58649; -.
DR Antibodypedia; 22306; 412 antibodies from 35 providers.
DR DNASU; 2267; -.
DR Ensembl; ENST00000381840.5; ENSP00000371262.2; ENSG00000104760.17.
DR Ensembl; ENST00000381841.4; ENSP00000371263.2; ENSG00000104760.17.
DR Ensembl; ENST00000398054.5; ENSP00000381131.1; ENSG00000104760.17.
DR Ensembl; ENST00000398056.6; ENSP00000381133.2; ENSG00000104760.17.
DR Ensembl; ENST00000427924.5; ENSP00000401952.1; ENSG00000104760.17.
DR Ensembl; ENST00000518650.5; ENSP00000428430.1; ENSG00000104760.17.
DR Ensembl; ENST00000522444.5; ENSP00000429757.1; ENSG00000104760.17.
DR GeneID; 2267; -.
DR KEGG; hsa:2267; -.
DR MANE-Select; ENST00000427924.5; ENSP00000401952.1; NM_004467.4; NP_004458.3.
DR UCSC; uc003wxx.4; human.
DR CTD; 2267; -.
DR DisGeNET; 2267; -.
DR GeneCards; FGL1; -.
DR HGNC; HGNC:3695; FGL1.
DR HPA; ENSG00000104760; Tissue enriched (liver).
DR MIM; 605776; gene.
DR neXtProt; NX_Q08830; -.
DR OpenTargets; ENSG00000104760; -.
DR PharmGKB; PA28133; -.
DR VEuPathDB; HostDB:ENSG00000104760; -.
DR eggNOG; KOG2579; Eukaryota.
DR GeneTree; ENSGT00940000160647; -.
DR HOGENOM; CLU_038628_1_3_1; -.
DR InParanoid; Q08830; -.
DR OMA; EQSGWWF; -.
DR OrthoDB; 523014at2759; -.
DR PhylomeDB; Q08830; -.
DR TreeFam; TF336658; -.
DR PathwayCommons; Q08830; -.
DR SignaLink; Q08830; -.
DR BioGRID-ORCS; 2267; 13 hits in 1070 CRISPR screens.
DR ChiTaRS; FGL1; human.
DR GeneWiki; FGL1; -.
DR GenomeRNAi; 2267; -.
DR Pharos; Q08830; Tbio.
DR PRO; PR:Q08830; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q08830; protein.
DR Bgee; ENSG00000104760; Expressed in right lobe of liver and 122 other tissues.
DR Genevisible; Q08830; HS.
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:0005577; C:fibrinogen complex; TAS:ProtInc.
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:0072574; P:hepatocyte proliferation; IDA:UniProtKB.
DR GO; GO:0050868; P:negative regulation of T cell activation; ISS:UniProtKB.
DR GO; GO:0050776; P:regulation of immune response; ISS: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; Direct protein sequencing; Disulfide bond;
KW Immunity; Reference proteome; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:11470158"
FT CHAIN 23..312
FT /note="Fibrinogen-like protein 1"
FT /id="PRO_0000009105"
FT DOMAIN 74..306
FT /note="Fibrinogen C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT COILED 23..61
FT /evidence="ECO:0000255"
FT DISULFID 26
FT /note="Interchain"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT DISULFID 83..112
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT DISULFID 248..261
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00739"
FT VARIANT 15
FT /note="T -> I (in dbSNP:rs484373)"
FT /evidence="ECO:0000269|PubMed:11470158,
FT ECO:0000269|PubMed:14702039, ECO:0000269|PubMed:8390249,
FT ECO:0000269|Ref.3, ECO:0000269|Ref.6"
FT /id="VAR_024002"
FT VARIANT 72
FT /note="I -> V (in dbSNP:rs3739406)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:8390249, ECO:0000269|Ref.3,
FT ECO:0000269|Ref.6"
FT /id="VAR_024003"
FT VARIANT 105
FT /note="P -> L (in dbSNP:rs2653406)"
FT /evidence="ECO:0000269|PubMed:11470158, ECO:0000269|Ref.6"
FT /id="VAR_024004"
FT VARIANT 111
FT /note="Y -> H (in dbSNP:rs34019703)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_024005"
FT VARIANT 114
FT /note="M -> V (in dbSNP:rs35311020)"
FT /id="VAR_049067"
FT VARIANT 121
FT /note="T -> S (in dbSNP:rs34239530)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_024006"
FT VARIANT 140
FT /note="Y -> F (in dbSNP:rs35431851)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_024007"
FT VARIANT 256
FT /note="W -> L (in dbSNP:rs2653414)"
FT /id="VAR_049068"
FT CONFLICT 69
FT /note="N -> D (in Ref. 1; BAA03336)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 312 AA; 36379 MW; 9297153AEA746C31 CRC64;
MAKVFSFILV TTALTMGREI SALEDCAQEQ MRLRAQVRLL ETRVKQQQVK IKQLLQENEV
QFLDKGDENT VIDLGSKRQY ADCSEIFNDG YKLSGFYKIK PLQSPAEFSV YCDMSDGGGW
TVIQRRSDGS ENFNRGWKDY ENGFGNFVQK HGEYWLGNKN LHFLTTQEDY TLKIDLADFE
KNSRYAQYKN FKVGDEKNFY ELNIGEYSGT AGDSLAGNFH PEVQWWASHQ RMKFSTWDRD
HDNYEGNCAE EDQSGWWFNR CHSANLNGVY YSGPYTAKTD NGIVWYTWHG WWYSLKSVVM
KIRPNDFIPN VI
