MFGM_MOUSE
ID MFGM_MOUSE Reviewed; 463 AA.
AC P21956; P97800; Q3TBN5; Q3U8S9; Q9R1X9; Q9WTS3;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=Lactadherin;
DE AltName: Full=MFGM;
DE AltName: Full=Milk fat globule-EGF factor 8;
DE Short=MFG-E8;
DE AltName: Full=SED1;
DE AltName: Full=Sperm surface protein SP47;
DE Short=MP47;
DE Flags: Precursor;
GN Name=Mfge8;
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] (ISOFORM 1), PROTEIN SEQUENCE OF 23-35, TISSUE
RP SPECIFICITY, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RC STRAIN=BALB/cJ; TISSUE=Mammary gland;
RX PubMed=2122462; DOI=10.1073/pnas.87.21.8417;
RA Stubbs J.D., Lekutis C., Singer K.L., Bui A., Yuzuki D., Srinivasan U.,
RA Parry G.;
RT "cDNA cloning of a mouse mammary epithelial cell surface protein reveals
RT the existence of epidermal growth factor-like domains linked to factor
RT VIII-like sequences.";
RL Proc. Natl. Acad. Sci. U.S.A. 87:8417-8421(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RA Ensslin M.A.;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 23-463 (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=9546740; DOI=10.1095/biolreprod58.4.1057;
RA Ensslin M.A., Vogel T., Calvete J.J., Thole H.H., Schmidtke J., Matsuda T.,
RA Toepfer-Petersen E.;
RT "Molecular cloning and characterization of P47, a novel boar sperm-
RT associated zona pellucida-binding protein homologous to a family of
RT mammalian secretory proteins.";
RL Biol. Reprod. 58:1057-1064(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, INDUCTION, AND GLYCOSYLATION.
RC STRAIN=BALB/cJ; TISSUE=Mammary gland;
RX PubMed=9920772; DOI=10.1006/bbrc.1998.0107;
RA Oshima K., Aoki N., Negi M., Kishi M., Kitajima K., Matsuda T.;
RT "Lactation-dependent expression of an mRNA splice variant with an exon for
RT a multiply O-glycosylated domain of mouse milk fat globule glycoprotein
RT MFG-E8.";
RL Biochem. Biophys. Res. Commun. 254:522-528(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC STRAIN=C57BL/6J, and NOD; TISSUE=Bone marrow, and Dendritic cell;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=FVB/N; TISSUE=Mammary gland;
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 [7]
RP INTERACTION WITH ITGB3 AND ITGB5, AND FUNCTION IN NEOVASCULARIZATION.
RX PubMed=15834428; DOI=10.1038/nm1233;
RA Silvestre J.S., Thery C., Hamard G., Boddaert J., Aguilar B., Delcayre A.,
RA Houbron C., Tamarat R., Blanc-Brude O., Heeneman S., Clergue M., Duriez M.,
RA Merval R., Levy B., Tedgui A., Amigorena S., Mallat Z.;
RT "Lactadherin promotes VEGF-dependent neovascularization.";
RL Nat. Med. 11:499-506(2005).
RN [8]
RP FUNCTION IN GUT EPITHELIAL REPAIR.
RX PubMed=18008006; DOI=10.1172/jci31841;
RA Bu H.F., Zuo X.L., Wang X., Ensslin M.A., Koti V., Hsueh W., Raymond A.S.,
RA Shur B.D., Tan X.D.;
RT "Milk fat globule-EGF factor 8/lactadherin plays a crucial role in
RT maintenance and repair of murine intestinal epithelium.";
RL J. Clin. Invest. 117:3673-3683(2007).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Heart, Lung, and Spleen;
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 [10]
RP STRUCTURE BY NMR OF 306-463, AND DISULFIDE BOND.
RX PubMed=23262193; DOI=10.1016/j.bbamem.2012.12.009;
RA Ye H., Li B., Subramanian V., Choi B.H., Liang Y., Harikishore A.,
RA Chakraborty G., Baek K., Yoon H.S.;
RT "NMR solution structure of C2 domain of MFG-E8 and insights into its
RT molecular recognition with phosphatidylserine.";
RL Biochim. Biophys. Acta 1828:1083-1093(2013).
CC -!- FUNCTION: Contributes to phagocytic removal of apoptotic cells in many
CC tissues. Specific ligand for the alpha-v/beta-3 and alpha-v/beta-5
CC receptors. Also binds to phosphatidylserine-enriched cell surfaces in a
CC receptor-independent manner. Zona pellucida-binding protein which may
CC play a role in gamete interaction (By similarity). Plays an important
CC role in the maintenance of intestinal epithelial homeostasis and the
CC promotion of mucosal healing. Promotes VEGF-dependent
CC neovascularization. {ECO:0000250, ECO:0000269|PubMed:15834428,
CC ECO:0000269|PubMed:18008006}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000269|PubMed:2122462}; Peripheral
CC membrane protein {ECO:0000269|PubMed:2122462}. Secreted
CC {ECO:0000269|PubMed:2122462}. Cytoplasmic vesicle, secretory vesicle,
CC acrosome membrane {ECO:0000250|UniProtKB:P79385}; Peripheral membrane
CC protein {ECO:0000250|UniProtKB:P79385}. Note=Located in the acrosomal
CC region of zona-pellucida bound sperm. {ECO:0000250|UniProtKB:P79385}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Long;
CC IsoId=P21956-1; Sequence=Displayed;
CC Name=2; Synonyms=Short;
CC IsoId=P21956-2; Sequence=VSP_009880;
CC -!- TISSUE SPECIFICITY: Mammary epithelial cell surfaces and spermatozoan.
CC Isoform 2 is present in brain, heart, kidney and spleen and at low
CC levels in lung, liver, small intestine and testis.
CC {ECO:0000269|PubMed:2122462, ECO:0000269|PubMed:9920772}.
CC -!- DEVELOPMENTAL STAGE: Isoform 1 and isoform 2 are detectable in mammary
CC tissue from non-pregnant animals, with isoform 2 being predominant.
CC Levels of isoform 1 increase during gestation and lactation while
CC levels of isoform 2 decrease. {ECO:0000269|PubMed:2122462,
CC ECO:0000269|PubMed:9920772}.
CC -!- INDUCTION: Isoform 1 is induced by insulin, prolactin and
CC hydrocortisone in mammary epithelial cells. Expression of isoform 2 is
CC repressed by the same treatment. {ECO:0000269|PubMed:9920772}.
CC -!- DOMAIN: The F5/8 type C 2 domain mediates high-affinity binding to
CC phosphatidylserine-containing membranes.
CC -!- PTM: N-glycosylated. Isoform 1 also exists in both an O-glycosylated
CC and a non-O-glycosylated form. {ECO:0000269|PubMed:9920772}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; M38337; AAA39534.1; -; mRNA.
DR EMBL; Y11684; CAA72380.2; -; mRNA.
DR EMBL; AB021130; BAA35180.1; -; mRNA.
DR EMBL; AB025280; BAA76386.1; -; mRNA.
DR EMBL; AK089211; BAC40794.1; -; mRNA.
DR EMBL; AK152088; BAE30938.1; -; mRNA.
DR EMBL; AK171143; BAE42274.1; -; mRNA.
DR EMBL; BC003892; AAH03892.1; -; mRNA.
DR EMBL; BC003904; AAH03904.1; -; mRNA.
DR CCDS; CCDS21379.1; -. [P21956-1]
DR CCDS; CCDS39989.1; -. [P21956-2]
DR PIR; A36479; A36479.
DR RefSeq; NP_032620.2; NM_008594.2. [P21956-1]
DR PDB; 2L9L; NMR; -; A=306-463.
DR PDBsum; 2L9L; -.
DR AlphaFoldDB; P21956; -.
DR SMR; P21956; -.
DR STRING; 10090.ENSMUSP00000032825; -.
DR GlyConnect; 2453; 2 N-Linked glycans (2 sites).
DR GlyGen; P21956; 4 sites, 2 N-linked glycans (2 sites).
DR PhosphoSitePlus; P21956; -.
DR CPTAC; non-CPTAC-3990; -.
DR EPD; P21956; -.
DR MaxQB; P21956; -.
DR PaxDb; P21956; -.
DR PeptideAtlas; P21956; -.
DR PRIDE; P21956; -.
DR ProteomicsDB; 252547; -. [P21956-1]
DR ProteomicsDB; 252548; -. [P21956-2]
DR Antibodypedia; 651; 640 antibodies from 36 providers.
DR DNASU; 17304; -.
DR Ensembl; ENSMUST00000032825; ENSMUSP00000032825; ENSMUSG00000030605. [P21956-1]
DR Ensembl; ENSMUST00000107409; ENSMUSP00000103032; ENSMUSG00000030605. [P21956-2]
DR GeneID; 17304; -.
DR KEGG; mmu:17304; -.
DR UCSC; uc009hxz.1; mouse. [P21956-1]
DR UCSC; uc009hyb.1; mouse. [P21956-2]
DR CTD; 4240; -.
DR MGI; MGI:102768; Mfge8.
DR VEuPathDB; HostDB:ENSMUSG00000030605; -.
DR eggNOG; ENOG502QVK3; Eukaryota.
DR GeneTree; ENSGT00940000156049; -.
DR HOGENOM; CLU_030066_0_1_1; -.
DR InParanoid; P21956; -.
DR OMA; YVKTFKV; -.
DR OrthoDB; 441415at2759; -.
DR PhylomeDB; P21956; -.
DR TreeFam; TF330156; -.
DR Reactome; R-MMU-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs).
DR Reactome; R-MMU-8957275; Post-translational protein phosphorylation.
DR BioGRID-ORCS; 17304; 0 hits in 77 CRISPR screens.
DR ChiTaRS; Mfge8; mouse.
DR PRO; PR:P21956; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; P21956; protein.
DR Bgee; ENSMUSG00000030605; Expressed in thoracic mammary gland and 275 other tissues.
DR ExpressionAtlas; P21956; baseline and differential.
DR Genevisible; P21956; MM.
DR GO; GO:0002080; C:acrosomal membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0009897; C:external side of plasma membrane; IDA:MGI.
DR GO; GO:0005615; C:extracellular space; IDA:MGI.
DR GO; GO:0019897; C:extrinsic component of plasma membrane; IDA:MGI.
DR GO; GO:0005178; F:integrin binding; IDA:BHF-UCL.
DR GO; GO:0008429; F:phosphatidylethanolamine binding; IDA:MGI.
DR GO; GO:0001786; F:phosphatidylserine binding; IDA:MGI.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0043277; P:apoptotic cell clearance; IDA:BHF-UCL.
DR GO; GO:0007155; P:cell adhesion; IEA:UniProtKB-KW.
DR GO; GO:0006911; P:phagocytosis, engulfment; IDA:MGI.
DR GO; GO:0006910; P:phagocytosis, recognition; IDA:MGI.
DR GO; GO:0050766; P:positive regulation of phagocytosis; IDA:MGI.
DR GO; GO:0007338; P:single fertilization; IEA:UniProtKB-KW.
DR CDD; cd00057; FA58C; 2.
DR InterPro; IPR000742; EGF-like_dom.
DR InterPro; IPR000421; FA58C.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR Pfam; PF00008; EGF; 2.
DR Pfam; PF00754; F5_F8_type_C; 2.
DR SMART; SM00181; EGF; 2.
DR SMART; SM00231; FA58C; 2.
DR SUPFAM; SSF49785; SSF49785; 2.
DR PROSITE; PS00022; EGF_1; 2.
DR PROSITE; PS01186; EGF_2; 2.
DR PROSITE; PS50026; EGF_3; 2.
DR PROSITE; PS01285; FA58C_1; 2.
DR PROSITE; PS01286; FA58C_2; 2.
DR PROSITE; PS50022; FA58C_3; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Angiogenesis; Cell adhesion;
KW Cytoplasmic vesicle; Direct protein sequencing; Disulfide bond;
KW EGF-like domain; Fertilization; Glycoprotein; Membrane; Reference proteome;
KW Repeat; Secreted; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:2122462"
FT CHAIN 23..463
FT /note="Lactadherin"
FT /id="PRO_0000007653"
FT DOMAIN 24..61
FT /note="EGF-like 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 64..108
FT /note="EGF-like 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00076"
FT DOMAIN 148..303
FT /note="F5/8 type C 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT DOMAIN 308..463
FT /note="F5/8 type C 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00081"
FT MOTIF 87..89
FT /note="Cell attachment site"
FT CARBOHYD 61
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 266
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 316
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 426
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 28..39
FT /evidence="ECO:0000250"
FT DISULFID 33..49
FT /evidence="ECO:0000250"
FT DISULFID 51..60
FT /evidence="ECO:0000250"
FT DISULFID 68..79
FT /evidence="ECO:0000250"
FT DISULFID 73..96
FT /evidence="ECO:0000250"
FT DISULFID 98..107
FT /evidence="ECO:0000250"
FT DISULFID 148..303
FT /evidence="ECO:0000250"
FT DISULFID 290..294
FT /evidence="ECO:0000250"
FT DISULFID 308..463
FT /evidence="ECO:0000269|PubMed:23262193"
FT VAR_SEQ 110..147
FT /note="ETNYYNLDGEYMFTTAVPNTAVPTPAPTPDLSNNLASR -> G (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334,
FT ECO:0000303|PubMed:16141072, ECO:0000303|PubMed:9546740,
FT ECO:0000303|PubMed:9920772, ECO:0000303|Ref.2"
FT /id="VSP_009880"
FT CONFLICT 35
FT /note="N -> D (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 168
FT /note="S -> Y (in Ref. 1; AAA39534)"
FT /evidence="ECO:0000305"
FT CONFLICT 196
FT /note="T -> H (in Ref. 1; AAA39534)"
FT /evidence="ECO:0000305"
FT CONFLICT 284
FT /note="K -> R (in Ref. 1; AAA39534, 3; CAA72380, 4;
FT BAA35180/BAA76386, 5; BAC40794/BAE42274 and 6; AAH03892/
FT AAH03904)"
FT /evidence="ECO:0000305"
FT CONFLICT 309
FT /note="S -> L (in Ref. 1; AAA39534)"
FT /evidence="ECO:0000305"
FT CONFLICT 395
FT /note="A -> E (in Ref. 1; AAA39534)"
FT /evidence="ECO:0000305"
FT STRAND 312..316
FT /evidence="ECO:0007829|PDB:2L9L"
FT STRAND 323..327
FT /evidence="ECO:0007829|PDB:2L9L"
FT STRAND 346..348
FT /evidence="ECO:0007829|PDB:2L9L"
FT STRAND 350..352
FT /evidence="ECO:0007829|PDB:2L9L"
FT STRAND 355..357
FT /evidence="ECO:0007829|PDB:2L9L"
FT STRAND 359..362
FT /evidence="ECO:0007829|PDB:2L9L"
FT STRAND 367..384
FT /evidence="ECO:0007829|PDB:2L9L"
FT STRAND 393..406
FT /evidence="ECO:0007829|PDB:2L9L"
FT STRAND 414..416
FT /evidence="ECO:0007829|PDB:2L9L"
FT TURN 425..427
FT /evidence="ECO:0007829|PDB:2L9L"
FT STRAND 430..432
FT /evidence="ECO:0007829|PDB:2L9L"
FT STRAND 434..436
FT /evidence="ECO:0007829|PDB:2L9L"
FT STRAND 438..453
FT /evidence="ECO:0007829|PDB:2L9L"
FT STRAND 455..462
FT /evidence="ECO:0007829|PDB:2L9L"
SQ SEQUENCE 463 AA; 51241 MW; 6E19CBB494B22878 CRC64;
MQVSRVLAAL CGMLLCASGL FAASGDFCDS SLCLNGGTCL TGQDNDIYCL CPEGFTGLVC
NETERGPCSP NPCYNDAKCL VTLDTQRGDI FTEYICQCPV GYSGIHCETE TNYYNLDGEY
MFTTAVPNTA VPTPAPTPDL SNNLASRCST QLGMEGGAIA DSQISASSVY MGFMGLQRWG
PELARLYRTG IVNAWTASNY DSKPWIQVNL LRKMRVSGVM TQGASRAGRA EYLKTFKVAY
SLDGRKFEFI QDESGGDKEF LGNLDNNSLK VNMFNPTLEA QYIKLYPVSC HRGCTLRFEL
LGCELHGCSE PLGLKNNTIP DSQMSASSSY KTWNLRAFGW YPHLGRLDNQ GKINAWTAQS
NSAKEWLQVD LGTQRQVTGI ITQGARDFGH IQYVASYKVA HSDDGVQWTV YEEQGSSKVF
QGNLDNNSHK KNIFEKPFMA RYVRVLPVSW HNRITLRLEL LGC
