MFNG_MOUSE
ID MFNG_MOUSE Reviewed; 321 AA.
AC O09008;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1997, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Beta-1,3-N-acetylglucosaminyltransferase manic fringe;
DE EC=2.4.1.222 {ECO:0000250|UniProtKB:O00587};
DE AltName: Full=O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase;
GN Name=Mfng;
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 [LARGE SCALE MRNA].
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 [4]
RP FUNCTION.
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).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 45-321 IN COMPLEX WITH UDP,
RP COFACTOR, MANGANESE-BINDING SITES, SUBSTRATE-BINDING SITES, ACTIVE SITE,
RP AND DISULFIDE BONDS.
RX PubMed=16964258; DOI=10.1038/nsmb1144;
RA Jinek M., Chen Y.W., Clausen H., Cohen S.M., Conti E.;
RT "Structural insights into the Notch-modifying glycosyltransferase Fringe.";
RL Nat. Struct. Mol. Biol. 13:945-946(2006).
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. {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 Evidence={ECO:0000250|UniProtKB:O00587};
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 Evidence={ECO:0000250|UniProtKB:O00587};
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:16964258};
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000250}; Single-
CC pass type II membrane protein {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 31 family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - GTase; Note=manic
CC fringe homolog (mfng);
CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_mou_591";
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DR EMBL; U94349; AAC53260.1; -; mRNA.
DR EMBL; AF015769; AAB71669.1; -; mRNA.
DR EMBL; BC010983; AAH10983.1; -; mRNA.
DR CCDS; CCDS27622.1; -.
DR RefSeq; NP_032621.1; NM_008595.2.
DR PDB; 2J0A; X-ray; 1.80 A; A=45-321.
DR PDB; 2J0B; X-ray; 2.10 A; A=45-321.
DR PDBsum; 2J0A; -.
DR PDBsum; 2J0B; -.
DR AlphaFoldDB; O09008; -.
DR SMR; O09008; -.
DR STRING; 10090.ENSMUSP00000018313; -.
DR CAZy; GT31; Glycosyltransferase Family 31.
DR GlyGen; O09008; 2 sites.
DR PhosphoSitePlus; O09008; -.
DR PaxDb; O09008; -.
DR PRIDE; O09008; -.
DR ProteomicsDB; 295937; -.
DR Antibodypedia; 25947; 205 antibodies from 29 providers.
DR DNASU; 17305; -.
DR Ensembl; ENSMUST00000018313; ENSMUSP00000018313; ENSMUSG00000018169.
DR GeneID; 17305; -.
DR KEGG; mmu:17305; -.
DR UCSC; uc007wri.1; mouse.
DR CTD; 4242; -.
DR MGI; MGI:1095404; Mfng.
DR VEuPathDB; HostDB:ENSMUSG00000018169; -.
DR eggNOG; ENOG502QV30; Eukaryota.
DR GeneTree; ENSGT00940000159564; -.
DR HOGENOM; CLU_056611_0_1_1; -.
DR InParanoid; O09008; -.
DR OMA; SHFVDTS; -.
DR OrthoDB; 826272at2759; -.
DR PhylomeDB; O09008; -.
DR TreeFam; TF324207; -.
DR BRENDA; 2.4.1.222; 3474.
DR BioGRID-ORCS; 17305; 1 hit in 72 CRISPR screens.
DR EvolutionaryTrace; O09008; -.
DR PRO; PR:O09008; -.
DR Proteomes; UP000000589; Chromosome 15.
DR RNAct; O09008; protein.
DR Bgee; ENSMUSG00000018169; Expressed in ventricular zone and 206 other tissues.
DR ExpressionAtlas; O09008; baseline and differential.
DR Genevisible; O09008; MM.
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; ISO:MGI.
DR GO; GO:0001825; P:blastocyst formation; IMP:MGI.
DR GO; GO:0002315; P:marginal zone B cell differentiation; IMP:UniProtKB.
DR GO; GO:0007389; P:pattern specification process; IEA:InterPro.
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; IMP:UniProtKB.
DR InterPro; IPR017374; Fringe.
DR InterPro; IPR003378; Fringe-like.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR Pfam; PF02434; Fringe; 1.
DR PIRSF; PIRSF038073; B-acetylgalactosaminyltfrase; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Developmental protein; Disulfide bond; Glycoprotein;
KW Glycosyltransferase; Golgi apparatus; Manganese; Membrane; Metal-binding;
KW Reference proteome; Signal-anchor; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..321
FT /note="Beta-1,3-N-acetylglucosaminyltransferase manic
FT fringe"
FT /id="PRO_0000219183"
FT TOPO_DOM 1..7
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 8..27
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 28..321
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT ACT_SITE 232
FT /evidence="ECO:0000305|PubMed:16964258"
FT BINDING 70
FT /ligand="substrate"
FT BINDING 143
FT /ligand="substrate"
FT BINDING 144
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT BINDING 256
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT CARBOHYD 109
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 185
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 110..121
FT /evidence="ECO:0000269|PubMed:16964258"
FT DISULFID 139..202
FT /evidence="ECO:0000269|PubMed:16964258"
FT DISULFID 306..315
FT /evidence="ECO:0000269|PubMed:16964258"
FT HELIX 53..55
FT /evidence="ECO:0007829|PDB:2J0A"
FT STRAND 56..61
FT /evidence="ECO:0007829|PDB:2J0A"
FT HELIX 64..66
FT /evidence="ECO:0007829|PDB:2J0A"
FT TURN 67..70
FT /evidence="ECO:0007829|PDB:2J0A"
FT HELIX 71..76
FT /evidence="ECO:0007829|PDB:2J0A"
FT HELIX 78..81
FT /evidence="ECO:0007829|PDB:2J0A"
FT HELIX 83..85
FT /evidence="ECO:0007829|PDB:2J0A"
FT STRAND 86..92
FT /evidence="ECO:0007829|PDB:2J0A"
FT HELIX 95..101
FT /evidence="ECO:0007829|PDB:2J0A"
FT HELIX 102..104
FT /evidence="ECO:0007829|PDB:2J0A"
FT STRAND 105..107
FT /evidence="ECO:0007829|PDB:2J0A"
FT HELIX 121..133
FT /evidence="ECO:0007829|PDB:2J0A"
FT STRAND 136..142
FT /evidence="ECO:0007829|PDB:2J0A"
FT STRAND 145..147
FT /evidence="ECO:0007829|PDB:2J0A"
FT HELIX 149..156
FT /evidence="ECO:0007829|PDB:2J0A"
FT STRAND 166..168
FT /evidence="ECO:0007829|PDB:2J0A"
FT HELIX 197..199
FT /evidence="ECO:0007829|PDB:2J0A"
FT STRAND 201..204
FT /evidence="ECO:0007829|PDB:2J0A"
FT HELIX 205..215
FT /evidence="ECO:0007829|PDB:2J0A"
FT TURN 224..228
FT /evidence="ECO:0007829|PDB:2J0A"
FT HELIX 231..241
FT /evidence="ECO:0007829|PDB:2J0A"
FT STRAND 247..249
FT /evidence="ECO:0007829|PDB:2J0A"
FT STRAND 256..258
FT /evidence="ECO:0007829|PDB:2J0A"
FT HELIX 260..262
FT /evidence="ECO:0007829|PDB:2J0A"
FT TURN 265..267
FT /evidence="ECO:0007829|PDB:2J0A"
FT HELIX 268..270
FT /evidence="ECO:0007829|PDB:2J0A"
FT STRAND 272..275
FT /evidence="ECO:0007829|PDB:2J0A"
FT STRAND 277..279
FT /evidence="ECO:0007829|PDB:2J0A"
FT STRAND 282..284
FT /evidence="ECO:0007829|PDB:2J0A"
FT TURN 294..296
FT /evidence="ECO:0007829|PDB:2J0A"
FT HELIX 301..308
FT /evidence="ECO:0007829|PDB:2J0A"
SQ SEQUENCE 321 AA; 36200 MW; 76EBCEC2314C50CD CRC64;
MHCRLFRGMA GALFTLLCVG LLSLRYHSSL SQRMIQGALR LNQRNPGPLE LQLGDIFIAV
KTTWAFHRSR LDLLLDTWVS RIRQQTFIFT DSPDERLQER LGPHLVVTNC SAEHSHPALS
CKMAAEFDAF LVSGLRWFCH VDDDNYVNPK ALLQLLKTFP QDRDVYVGKP SLNRPIHASE
LQSKNRTKLV RFWFATGGAG FCINRQLALK MVPWASGSHF VDTSALIRLP DDCTVGYIIE
CKLGGRLQPS PLFHSHLETL QLLGAAQLPE QVTLSYGVFE GKLNVIKLPG PFSHEEDPSR
FRSLHCLLYP DTPWCPLLAA P
