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 27-MAR-2024, entry version 173. DE RecName: Full=Beta-1,3-N-acetylglucosaminyltransferase manic fringe {ECO:0000305}; DE EC=2.4.1.222 {ECO:0000250|UniProtKB:O09008}; DE AltName: Full=O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase; GN Name=MFNG {ECO:0000312|HGNC:HGNC:7038}; 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). 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 (By similarity). Modulates NOTCH1 activity by CC modifying O-fucose residues at specific EGF-like domains resulting in CC 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 -!- 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:O09008}; 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:O09008}; CC -!- COFACTOR: CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000250|UniProtKB:O09008}; CC Note=Has some activity with cobalt, magnesium and calcium, but not CC zinc. {ECO:0000250|UniProtKB:O09008}; 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; CC Note=Beta-1,3-N-acetylglucosaminyltransferase manic fringe; CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_552"; 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; 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 GlyCosmos; O00587; 2 sites, No reported glycans. DR GlyGen; O00587; 3 sites. DR iPTMnet; O00587; -. DR PhosphoSitePlus; O00587; -. DR BioMuta; MFNG; -. DR MassIVE; O00587; -. DR MaxQB; O00587; -. DR PaxDb; 9606-ENSP00000349490; -. DR PeptideAtlas; O00587; -. DR ProteomicsDB; 47988; -. [O00587-1] DR ProteomicsDB; 47989; -. [O00587-2] DR Antibodypedia; 25947; 237 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 AGR; HGNC:7038; -. 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; GSHFVDT; -. DR OrthoDB; 2902544at2759; -. 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 1153 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 167 other cell types or tissues. DR ExpressionAtlas; O00587; baseline and differential. DR GO; GO:0005615; C:extracellular space; TAS:ProtInc. DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. 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:0008593; P:regulation of Notch signaling pathway; ISS:UniProtKB. DR Gene3D; 3.90.550.50; -; 1. DR InterPro; IPR017374; Fringe. DR InterPro; IPR003378; Fringe-like_glycosylTrfase. DR PANTHER; PTHR10811:SF6; BETA-1,3-N-ACETYLGLUCOSAMINYLTRANSFERASE MANIC FRINGE; 1. DR PANTHER; PTHR10811; FRINGE-RELATED; 1. DR Pfam; PF02434; Fringe; 1. DR PIRSF; PIRSF038073; B-acetylgalactosaminyltfrase; 1. DR Genevisible; O00587; HS. PE 2: Evidence at transcript 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 //