MFNG_HUMAN
ID MFNG_HUMAN Reviewed; 321 AA.
AC O00587; B4DLT6; O43730; Q504S9;
DT 27-MAR-2002, integrated into UniProtKB/Swiss-Prot.
DT 27-MAR-2002, sequence version 2.
DT 03-AUG-2022, entry version 164.
DE RecName: Full=Beta-1,3-N-acetylglucosaminyltransferase manic fringe;
DE EC=2.4.1.222;
DE AltName: Full=O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase;
GN Name=MFNG;
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] (ISOFORM 1).
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 [LARGE SCALE MRNA] (ISOFORM 1).
RX PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA Beare D.M., Dunham I.;
RT "A genome annotation-driven approach to cloning the human ORFeome.";
RL Genome Biol. 5:R84.1-R84.11(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=10591208; DOI=10.1038/990031;
RA Dunham I., Hunt A.R., Collins J.E., Bruskiewich R., Beare D.M., Clamp M.,
RA Smink L.J., Ainscough R., Almeida J.P., Babbage A.K., Bagguley C.,
RA Bailey J., Barlow K.F., Bates K.N., Beasley O.P., Bird C.P., Blakey S.E.,
RA Bridgeman A.M., Buck D., Burgess J., Burrill W.D., Burton J., Carder C.,
RA Carter N.P., Chen Y., Clark G., Clegg S.M., Cobley V.E., Cole C.G.,
RA Collier R.E., Connor R., Conroy D., Corby N.R., Coville G.J., Cox A.V.,
RA Davis J., Dawson E., Dhami P.D., Dockree C., Dodsworth S.J., Durbin R.M.,
RA Ellington A.G., Evans K.L., Fey J.M., Fleming K., French L., Garner A.A.,
RA Gilbert J.G.R., Goward M.E., Grafham D.V., Griffiths M.N.D., Hall C.,
RA Hall R.E., Hall-Tamlyn G., Heathcott R.W., Ho S., Holmes S., Hunt S.E.,
RA Jones M.C., Kershaw J., Kimberley A.M., King A., Laird G.K., Langford C.F.,
RA Leversha M.A., Lloyd C., Lloyd D.M., Martyn I.D., Mashreghi-Mohammadi M.,
RA Matthews L.H., Mccann O.T., Mcclay J., Mclaren S., McMurray A.A.,
RA Milne S.A., Mortimore B.J., Odell C.N., Pavitt R., Pearce A.V., Pearson D.,
RA Phillimore B.J.C.T., Phillips S.H., Plumb R.W., Ramsay H., Ramsey Y.,
RA Rogers L., Ross M.T., Scott C.E., Sehra H.K., Skuce C.D., Smalley S.,
RA Smith M.L., Soderlund C., Spragon L., Steward C.A., Sulston J.E.,
RA Swann R.M., Vaudin M., Wall M., Wallis J.M., Whiteley M.N., Willey D.L.,
RA Williams L., Williams S.A., Williamson H., Wilmer T.E., Wilming L.,
RA Wright C.L., Hubbard T., Bentley D.R., Beck S., Rogers J., Shimizu N.,
RA Minoshima S., Kawasaki K., Sasaki T., Asakawa S., Kudoh J., Shintani A.,
RA Shibuya K., Yoshizaki Y., Aoki N., Mitsuyama S., Roe B.A., Chen F., Chu L.,
RA Crabtree J., Deschamps S., Do A., Do T., Dorman A., Fang F., Fu Y., Hu P.,
RA Hua A., Kenton S., Lai H., Lao H.I., Lewis J., Lewis S., Lin S.-P., Loh P.,
RA Malaj E., Nguyen T., Pan H., Phan S., Qi S., Qian Y., Ray L., Ren Q.,
RA Shaull S., Sloan D., Song L., Wang Q., Wang Y., Wang Z., White J.,
RA Willingham D., Wu H., Yao Z., Zhan M., Zhang G., Chissoe S., Murray J.,
RA Miller N., Minx P., Fulton R., Johnson D., Bemis G., Bentley D.,
RA Bradshaw H., Bourne S., Cordes M., Du Z., Fulton L., Goela D., Graves T.,
RA Hawkins J., Hinds K., Kemp K., Latreille P., Layman D., Ozersky P.,
RA Rohlfing T., Scheet P., Walker C., Wamsley A., Wohldmann P., Pepin K.,
RA Nelson J., Korf I., Bedell J.A., Hillier L.W., Mardis E., Waterston R.,
RA Wilson R., Emanuel B.S., Shaikh T., Kurahashi H., Saitta S., Budarf M.L.,
RA McDermid H.E., Johnson A., Wong A.C.C., Morrow B.E., Edelmann L., Kim U.J.,
RA Shizuya H., Simon M.I., Dumanski J.P., Peyrard M., Kedra D., Seroussi E.,
RA Fransson I., Tapia I., Bruder C.E., O'Brien K.P., Wilkinson P.,
RA Bodenteich A., Hartman K., Hu X., Khan A.S., Lane L., Tilahun Y.,
RA Wright H.;
RT "The DNA sequence of human chromosome 22.";
RL Nature 402:489-495(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Lymph;
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 [6]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=10935626; DOI=10.1038/35019000;
RA Moloney D.J., Panin V.M., Johnston S.H., Chen J., Shao L., Wilson R.,
RA Wang Y., Stanley P., Irvine K.D., Haltiwanger R.S., Vogt T.F.;
RT "Fringe is a glycosyltransferase that modifies Notch.";
RL Nature 406:369-375(2000).
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 (PubMed:10935626). Modulates NOTCH1 activity
CC by modifying O-fucose residues at specific EGF-like domains resulting
CC in inhibition of NOTCH1 activation by JAG1 and enhancement of NOTCH1
CC activation by DLL1 via an increase in its binding to DLL1 (By
CC similarity). {ECO:0000250|UniProtKB:O09008,
CC ECO:0000269|PubMed:10935626}.
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:0000269|PubMed:10935626};
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:0000269|PubMed:10935626};
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=O00587-1; Sequence=Displayed;
CC Name=2;
CC IsoId=O00587-2; Sequence=VSP_042857;
CC -!- SIMILARITY: Belongs to the glycosyltransferase 31 family.
CC {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - GTase; Note=Beta-1,3-
CC N-acetylglucosaminyltransferase manic fringe;
CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_552";
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DR EMBL; U94352; AAC51358.1; -; mRNA.
DR EMBL; CR456518; CAG30404.1; -; mRNA.
DR EMBL; AK297149; BAG59648.1; -; mRNA.
DR EMBL; Z93096; CAB07511.1; -; Genomic_DNA.
DR EMBL; BC094814; AAH94814.1; -; mRNA.
DR CCDS; CCDS13947.1; -. [O00587-1]
DR CCDS; CCDS54525.1; -. [O00587-2]
DR RefSeq; NP_001159815.1; NM_001166343.1. [O00587-2]
DR RefSeq; NP_002396.2; NM_002405.3. [O00587-1]
DR AlphaFoldDB; O00587; -.
DR SMR; O00587; -.
DR BioGRID; 110400; 146.
DR STRING; 9606.ENSP00000349490; -.
DR CAZy; GT31; Glycosyltransferase Family 31.
DR GlyGen; O00587; 3 sites.
DR iPTMnet; O00587; -.
DR PhosphoSitePlus; O00587; -.
DR BioMuta; MFNG; -.
DR MassIVE; O00587; -.
DR MaxQB; O00587; -.
DR PaxDb; O00587; -.
DR PeptideAtlas; O00587; -.
DR PRIDE; O00587; -.
DR ProteomicsDB; 47988; -. [O00587-1]
DR ProteomicsDB; 47989; -. [O00587-2]
DR Antibodypedia; 25947; 205 antibodies from 29 providers.
DR DNASU; 4242; -.
DR Ensembl; ENST00000356998.8; ENSP00000349490.3; ENSG00000100060.18. [O00587-1]
DR Ensembl; ENST00000416983.7; ENSP00000413855.3; ENSG00000100060.18. [O00587-2]
DR GeneID; 4242; -.
DR KEGG; hsa:4242; -.
DR MANE-Select; ENST00000356998.8; ENSP00000349490.3; NM_002405.4; NP_002396.2.
DR UCSC; uc003ass.3; human. [O00587-1]
DR CTD; 4242; -.
DR GeneCards; MFNG; -.
DR HGNC; HGNC:7038; MFNG.
DR HPA; ENSG00000100060; Tissue enhanced (lymphoid).
DR MIM; 602577; gene.
DR neXtProt; NX_O00587; -.
DR OpenTargets; ENSG00000100060; -.
DR PharmGKB; PA30775; -.
DR VEuPathDB; HostDB:ENSG00000100060; -.
DR eggNOG; ENOG502QV30; Eukaryota.
DR GeneTree; ENSGT00940000159564; -.
DR HOGENOM; CLU_056611_0_1_1; -.
DR InParanoid; O00587; -.
DR OMA; SHFVDTS; -.
DR OrthoDB; 826272at2759; -.
DR PhylomeDB; O00587; -.
DR TreeFam; TF324207; -.
DR BRENDA; 2.4.1.222; 2681.
DR PathwayCommons; O00587; -.
DR Reactome; R-HSA-1912420; Pre-NOTCH Processing in Golgi.
DR SignaLink; O00587; -.
DR SIGNOR; O00587; -.
DR BioGRID-ORCS; 4242; 20 hits in 1071 CRISPR screens.
DR GeneWiki; MFNG; -.
DR GenomeRNAi; 4242; -.
DR Pharos; O00587; Tbio.
DR PRO; PR:O00587; -.
DR Proteomes; UP000005640; Chromosome 22.
DR RNAct; O00587; protein.
DR Bgee; ENSG00000100060; Expressed in granulocyte and 165 other tissues.
DR ExpressionAtlas; O00587; baseline and differential.
DR Genevisible; O00587; HS.
DR GO; GO:0005615; C:extracellular space; TAS:ProtInc.
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:FlyBase.
DR GO; GO:0001825; P:blastocyst formation; IEA:Ensembl.
DR GO; GO:0002315; P:marginal zone B cell differentiation; ISS:UniProtKB.
DR GO; GO:0007389; P:pattern specification process; TAS:ProtInc.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0032092; P:positive regulation of protein binding; IEA:Ensembl.
DR GO; GO:0008593; P:regulation of Notch signaling pathway; ISS: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 Alternative splicing; 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_0000219182"
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:0000250"
FT BINDING 70
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 143
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 144
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250"
FT BINDING 256
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250"
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:0000250"
FT DISULFID 139..202
FT /evidence="ECO:0000250"
FT DISULFID 306..315
FT /evidence="ECO:0000250"
FT VAR_SEQ 86..102
FT /note="TFVFTDSPDKGLQERLG -> VTR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042857"
FT VARIANT 302
FT /note="R -> C (in dbSNP:rs8192548)"
FT /id="VAR_024467"
FT CONFLICT 85
FT /note="Q -> L (in Ref. 1; AAC51358)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 321 AA; 36202 MW; 7CB847E7423DD0BC CRC64;
MQCRLPRGLA GALLTLLCMG LLCLRYHLNL SPQRVQGTPE LSQPNPGPPK LQLHDVFIAV
KTTRAFHRLR LELLLDTWVS RTREQTFVFT DSPDKGLQER LGSHLVVTNC SAEHSHPALS
CKMAAEFDTF LASGLRWFCH VDDDNYVNPR ALLQLLRAFP LARDVYVGRP SLNRPIHASE
PQPHNRTRLV QFWFATGGAG FCINRKLALK MAPWASGSRF MDTSALIRLP DDCTMGYIIE
CKLGGRLQPS PLFHSHLETL QLLRTAQLPE QVTLSYGVFE GKLNVIKLQG PFSPEEDPSR
FRSLHCLLYP DTPWCPQLGA R
