LFNG_MOUSE
ID LFNG_MOUSE Reviewed; 378 AA.
AC O09010; Q3U659; Q8K3F1; Q9DC10;
DT 10-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Beta-1,3-N-acetylglucosaminyltransferase lunatic fringe;
DE EC=2.4.1.222;
DE AltName: Full=O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase;
GN Name=Lfng;
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].
RX PubMed=9187150; DOI=10.1242/dev.124.11.2245;
RA Johnston S.H., Rauskolb C., Wilson R., Prabhakaran B., Irvine K.D.,
RA Vogt T.F.;
RT "A family of mammalian Fringe genes implicated in boundary determination
RT and the Notch pathway.";
RL Development 124:2245-2254(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9207795; DOI=10.1038/ng0797-283;
RA Cohen B., Bashirullah A., Dagnino L., Campbell C., Fisher W.W., Leow C.C.,
RA Whiting E., Ryan D., Zinyk D., Boulianne G., Hui C.-C., Gallie B.,
RA Phillips R.A., Lipshitz H.D., Egan S.E.;
RT "Fringe boundaries coincide with Notch-dependent patterning centres in
RT mammals and alter Notch-dependent development in Drosophila.";
RL Nat. Genet. 16:283-288(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE OF 1-143, AND DEVELOPMENTAL STAGE.
RC STRAIN=129S6/SvEvTac;
RX PubMed=12110169; DOI=10.1016/s1534-5807(02)00212-5;
RA Cole S.E., Levorse J.M., Tilghman S.M., Vogt T.F.;
RT "Clock regulatory elements control cyclic expression of Lunatic fringe
RT during somitogenesis.";
RL Dev. Cell 3:75-84(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Bone marrow, and Lung;
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 [5]
RP FUNCTION.
RX PubMed=10330372; DOI=10.1016/s0960-9822(99)80212-7;
RA del Barco Barrantes I., Elia A.J., Wuensch K., De Angelis M.H., Mak T.W.,
RA Rossant J., Conlon R.A., Gossler A., de la Pompa J.L.;
RT "Interaction between Notch signalling and Lunatic fringe during somite
RT boundary formation in the mouse.";
RL Curr. Biol. 9:470-480(1999).
RN [6]
RP FUNCTION.
RX PubMed=12167404; DOI=10.1006/dbio.2002.0734;
RA Mustonen T., Tuemmers M., Mikami T., Itoh N., Zhang N., Gridley T.,
RA Thesleff I.;
RT "Lunatic fringe, FGF, and BMP regulate the Notch pathway during epithelial
RT morphogenesis of teeth.";
RL Dev. Biol. 248:281-293(2002).
RN [7]
RP DEVELOPMENTAL STAGE.
RX PubMed=9690473; DOI=10.1038/28632;
RA Evrard Y.A., Lun Y., Aulehla A., Gan L., Johnson R.L.;
RT "Lunatic fringe is an essential mediator of somite segmentation and
RT patterning.";
RL Nature 394:377-381(1998).
RN [8]
RP DEVELOPMENTAL STAGE.
RX PubMed=10341080; DOI=10.1007/s003359901039;
RA Moran J.L., Johnston S.H., Rauskolb C., Bhalerao J., Bowcock A.M.,
RA Vogt T.F.;
RT "Genomic structure, mapping, and expression analysis of the mammalian
RT Lunatic, Manic, and Radical fringe genes.";
RL Mamm. Genome 10:535-541(1999).
RN [9]
RP FUNCTION.
RX PubMed=11520458; DOI=10.1016/s1074-7613(01)00189-3;
RA Koch U., Lacombe T.A., Holland D., Bowman J.L., Cohen B.L., Egan S.E.,
RA Guidos C.J.;
RT "Subversion of the T/B lineage decision in the thymus by lunatic fringe-
RT mediated inhibition of Notch-1.";
RL Immunity 15:225-236(2001).
RN [10]
RP DEVELOPMENTAL STAGE.
RX PubMed=12110168; DOI=10.1016/s1534-5807(02)00211-3;
RA Morales A.V., Yasuda Y., Ish-Horowicz D.;
RT "Periodic Lunatic fringe expression is controlled during segmentation by a
RT cyclic transcriptional enhancer responsive to notch signaling.";
RL Dev. Cell 3:63-74(2002).
RN [11]
RP FUNCTION, AND INTERACTION WITH NOTCH1.
RX PubMed=28089369; DOI=10.1016/j.devcel.2016.12.013;
RA Kakuda S., Haltiwanger R.S.;
RT "Deciphering the fringe-mediated notch code: identification of activating
RT and inhibiting sites allowing discrimination between ligands.";
RL Dev. Cell 40:193-201(2017).
CC -!- FUNCTION: Glycosyltransferase that initiates the elongation of O-linked
CC fucose residues attached to EGF-like repeats in the extracellular
CC domain of Notch molecules. Modulates NOTCH1 activity by modifying O-
CC fucose residues at specific EGF-like domains resulting in inhibition of
CC NOTCH1 activation by JAG1 and enhancement of NOTCH1 activation by DLL1
CC via an increase in its binding to DLL1 (PubMed:28089369). Decreases the
CC binding of JAG1 to NOTCH2 but not that of DLL1 (By similarity).
CC Essential mediator of somite segmentation and patterning. During somite
CC boundary formation, it restricts Notch activity in the presomitic
CC mesoderm to a boundary-forming territory in the posterior half of the
CC prospective somite. In this region, Notch function activates a set of
CC genes that are involved in boundary formation and in anterior-posterior
CC somite identity (PubMed:10330372). Ectopically expressed in the thymus,
CC Lfgn inhibits Notch signaling which results in inhibition of T-cell
CC commitment and promotes B-cell development in lymphoid progenitors
CC (PubMed:11520458). May play a role in boundary formation of the enamel
CC knot (PubMed:12167404). {ECO:0000250|UniProtKB:Q8NES3,
CC ECO:0000269|PubMed:10330372, ECO:0000269|PubMed:11520458,
CC ECO:0000269|PubMed:12167404, ECO:0000269|PubMed:28089369}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-O-(alpha-L-fucosyl)-L-threonyl-[EGF-like domain protein] +
CC UDP-N-acetyl-alpha-D-glucosamine = 3-O-(N-acetyl-beta-D-glucosaminyl-
CC (1->3)-alpha-L-fucosyl)-L-threonyl-[EGF-like domain protein] + H(+) +
CC UDP; Xref=Rhea:RHEA:70531, Rhea:RHEA-COMP:17922, Rhea:RHEA-
CC COMP:17923, ChEBI:CHEBI:15378, ChEBI:CHEBI:57705, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:189631, ChEBI:CHEBI:189634; EC=2.4.1.222;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-O-(alpha-L-fucosyl)-L-seryl-[EGF-like domain protein] + UDP-
CC N-acetyl-alpha-D-glucosamine = 3-O-(N-acetyl-beta-D-glucosaminyl-
CC (1->3)-alpha-L-fucosyl)-L-seryl-[EGF-like domain protein] + H(+) +
CC UDP; Xref=Rhea:RHEA:70511, Rhea:RHEA-COMP:17919, Rhea:RHEA-
CC COMP:17920, ChEBI:CHEBI:15378, ChEBI:CHEBI:57705, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:189632, ChEBI:CHEBI:189633; EC=2.4.1.222;
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000250}; Single-
CC pass type II membrane protein {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Detected at 12.5 dpc in all tissues examined with
CC the highest level observed in adult brain and spleen. Detected in the
CC dental epithelium.
CC -!- DEVELOPMENTAL STAGE: Developmental protein. During segmentation it
CC shows a cyclic transcription pattern which is under the control of
CC Notch. Expressed in the caudal region of the presomitic mesoderm with
CC each cycle corresponding to the formation time of one somite. In the
CC dental epithelium it is detected at stage 13.5 dpc. The pattern of
CC expression corresponds exactly to the formation of the enamel knot
CC between late bud and early cap stages. {ECO:0000269|PubMed:10341080,
CC ECO:0000269|PubMed:12110168, ECO:0000269|PubMed:12110169,
CC ECO:0000269|PubMed:9690473}.
CC -!- PTM: A soluble form may be derived from the membrane form by
CC proteolytic processing.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 31 family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - GTase; Note=lunatic
CC fringe gene homolog (lfng);
CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_mou_590";
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DR EMBL; U94351; AAC53262.1; -; mRNA.
DR EMBL; AF015768; AAB71668.1; -; mRNA.
DR EMBL; AY124581; AAM93541.1; -; Genomic_DNA.
DR EMBL; AK004642; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AK153283; BAE31866.1; -; mRNA.
DR CCDS; CCDS19821.1; -.
DR RefSeq; NP_032520.1; NM_008494.3.
DR AlphaFoldDB; O09010; -.
DR SMR; O09010; -.
DR STRING; 10090.ENSMUSP00000031555; -.
DR CAZy; GT31; Glycosyltransferase Family 31.
DR GlyGen; O09010; 1 site.
DR iPTMnet; O09010; -.
DR PhosphoSitePlus; O09010; -.
DR jPOST; O09010; -.
DR MaxQB; O09010; -.
DR PaxDb; O09010; -.
DR PRIDE; O09010; -.
DR ProteomicsDB; 265064; -.
DR Antibodypedia; 24378; 329 antibodies from 32 providers.
DR DNASU; 16848; -.
DR Ensembl; ENSMUST00000031555; ENSMUSP00000031555; ENSMUSG00000029570.
DR GeneID; 16848; -.
DR KEGG; mmu:16848; -.
DR UCSC; uc009ahu.1; mouse.
DR CTD; 3955; -.
DR MGI; MGI:1095413; Lfng.
DR VEuPathDB; HostDB:ENSMUSG00000029570; -.
DR eggNOG; ENOG502QV30; Eukaryota.
DR GeneTree; ENSGT00940000158717; -.
DR HOGENOM; CLU_056611_0_1_1; -.
DR InParanoid; O09010; -.
DR OMA; SENKMRP; -.
DR OrthoDB; 826272at2759; -.
DR PhylomeDB; O09010; -.
DR TreeFam; TF324207; -.
DR BRENDA; 2.4.1.222; 3474.
DR BioGRID-ORCS; 16848; 2 hits in 76 CRISPR screens.
DR PRO; PR:O09010; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; O09010; protein.
DR Bgee; ENSMUSG00000029570; Expressed in embryonic post-anal tail and 231 other tissues.
DR ExpressionAtlas; O09010; baseline and differential.
DR Genevisible; O09010; MM.
DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome.
DR GO; GO:0030173; C:integral component of Golgi membrane; IEA:InterPro.
DR GO; GO:0008375; F:acetylglucosaminyltransferase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0033829; F:O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase activity; IDA:UniProtKB.
DR GO; GO:0007386; P:compartment pattern specification; IMP:MGI.
DR GO; GO:0002315; P:marginal zone B cell differentiation; IMP:UniProtKB.
DR GO; GO:1902367; P:negative regulation of Notch signaling pathway involved in somitogenesis; IMP:UniProtKB.
DR GO; GO:0001541; P:ovarian follicle development; IMP:MGI.
DR GO; GO:0051446; P:positive regulation of meiotic cell cycle; IMP:MGI.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IDA:MGI.
DR GO; GO:0032092; P:positive regulation of protein binding; IDA:MGI.
DR GO; GO:0008593; P:regulation of Notch signaling pathway; IDA:UniProtKB.
DR GO; GO:0014807; P:regulation of somitogenesis; IMP:MGI.
DR GO; GO:0001756; P:somitogenesis; IMP:UniProtKB.
DR GO; GO:0030217; P:T cell differentiation; IMP:UniProtKB.
DR InterPro; IPR017374; Fringe.
DR InterPro; IPR003378; Fringe-like.
DR Pfam; PF02434; Fringe; 1.
DR PIRSF; PIRSF038073; B-acetylgalactosaminyltfrase; 1.
PE 1: Evidence at protein level;
KW Developmental protein; Disulfide bond; Glycoprotein; Glycosyltransferase;
KW Golgi apparatus; Manganese; Membrane; Metal-binding; Reference proteome;
KW Signal-anchor; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..378
FT /note="Beta-1,3-N-acetylglucosaminyltransferase lunatic
FT fringe"
FT /id="PRO_0000219177"
FT TOPO_DOM 1..8
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 9..29
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 30..378
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 85..108
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 289
FT /evidence="ECO:0000250"
FT BINDING 128
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 200
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 201
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250"
FT BINDING 313
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250"
FT SITE 85..86
FT /note="Cleavage; by furin-like protease"
FT /evidence="ECO:0000255"
FT CARBOHYD 166
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 167..178
FT /evidence="ECO:0000250"
FT DISULFID 196..259
FT /evidence="ECO:0000250"
FT DISULFID 363..372
FT /evidence="ECO:0000250"
FT CONFLICT 343
FT /note="V -> M (in Ref. 4; AK004642)"
FT /evidence="ECO:0000305"
FT CONFLICT 361
FT /note="V -> I (in Ref. 4; AK004642)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 378 AA; 41952 MW; FD0A02597BF9AFED CRC64;
MLQRCGRRLL LALVGALLAC LLVLTADPPP TPMPAERGRR ALRSLAGSSG GAPASGSRAA
VDPGVLTREV HSLSEYFSLL TRARRDADPP PGVASRQGDG HPRPPAEVLS PRDVFIAVKT
TRKFHRARLD LLFETWISRH KEMTFIFTDG EDEALAKLTG NVVLTNCSSA HSRQALSCKM
AVEYDRFIES GKKWFCHVDD DNYVNLRALL RLLASYPHTQ DVYIGKPSLD RPIQATERIS
EHKVRPVHFW FATGGAGFCI SRGLALKMGP WASGGHFMST AERIRLPDDC TIGYIVEALL
GVPLIRSGLF HSHLENLQQV PTTELHEQVT LSYGMFENKR NAVHIKGPFS VEADPSRFRS
VHCHLYPDTP WCPRSAIF
