ID OFUT1_DROME Reviewed; 402 AA. AC Q9V6X7; Q5BIC9; Q86SA7; Q8MSR1; DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-2000, sequence version 1. DT 24-JAN-2024, entry version 158. DE RecName: Full=GDP-fucose protein O-fucosyltransferase 1; DE EC=2.4.1.221 {ECO:0000269|PubMed:12909620}; DE AltName: Full=Neurotic protein; DE AltName: Full=Peptide-O-fucosyltransferase 1; DE Short=O-FucT-1; DE Flags: Precursor; GN Name=O-fut1; Synonyms=nti; ORFNames=CG12366; OS Drosophila melanogaster (Fruit fly). OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; OC Drosophilidae; Drosophila; Sophophora. OX NCBI_TaxID=7227; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND DEVELOPMENTAL STAGE. RX PubMed=12917292; DOI=10.1242/dev.00679; RA Sasamura T., Sasaki N., Miyashita F., Nakao S., Ishikawa H., Ito M., RA Kitagawa M., Harigaya K., Spana E., Bilder D., Perrmon N., Matsuno K.; RT "Neurotic, a novel maternal neurogenic gene, encodes an O- RT fucosyltransferase that is essential for Notch-Delta interactions."; RL Development 130:4785-4795(2003). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=Berkeley; RX PubMed=10731132; DOI=10.1126/science.287.5461.2185; RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D., RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F., RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N., RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C., RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C., RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A., RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A., RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V., RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J., RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E., RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B., RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I., RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C., RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S., RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M., RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M., RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D., RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F., RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D., RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A., RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C., RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C., RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L., RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R., RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V., RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F., RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J., RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R., RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y., RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T., RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S., RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W., RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M., RA Venter J.C.; RT "The genome sequence of Drosophila melanogaster."; RL Science 287:2185-2195(2000). RN [3] RP GENOME REANNOTATION. RC STRAIN=Berkeley; RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083; RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S., RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E., RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P., RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A., RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M., RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.; RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic RT review."; RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=Berkeley; TISSUE=Embryo; RA Stapleton M., Carlson J.W., Chavez C., Frise E., George R.A., Pacleb J.M., RA Park S., Wan K.H., Yu C., Rubin G.M., Celniker S.E.; RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 11-402. RC STRAIN=Berkeley; TISSUE=Embryo; RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080; RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A., RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M., RA Celniker S.E.; RT "A Drosophila full-length cDNA resource."; RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002). RN [6] RP HOMOLOGY. RX PubMed=11524432; DOI=10.1074/jbc.m107849200; RA Wang Y., Shao L., Shi S., Harris R.J., Spellman M.W., Stanley P., RA Haltiwanger R.S.; RT "Modification of epidermal growth factor-like repeats with O-fucose: RT molecular cloning and expression of a novel GDP-fucose protein O- RT fucosyltransferase."; RL J. Biol. Chem. 276:40338-40345(2001). RN [7] RP HOMOLOGY. RX PubMed=11698403; DOI=10.1074/jbc.m107927200; RA Roos C., Kolmer M., Mattila P., Renkonen R.; RT "Composition of Drosophila melanogaster proteome involved in fucosylated RT glycan metabolism."; RL J. Biol. Chem. 277:3168-3175(2002). RN [8] RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY. RX PubMed=12909620; DOI=10.1074/jbc.m308687200; RA Okajima T., Xu A., Irvine K.D.; RT "Modulation of notch-ligand binding by protein O-fucosyltransferase 1 and RT fringe."; RL J. Biol. Chem. 278:42340-42345(2003). RN [9] RP FUNCTION, AND INTERACTION WITH N. RX PubMed=17329366; DOI=10.1242/dev.02811; RA Sasamura T., Ishikawa H.O., Sasaki N., Higashi S., Kanai M., Nakao S., RA Ayukawa T., Aigaki T., Noda K., Miyoshi E., Taniguchi N., Matsuno K.; RT "The O-fucosyltransferase O-fut1 is an extracellular component that is RT essential for the constitutive endocytic trafficking of Notch in RT Drosophila."; RL Development 134:1347-1356(2007). CC -!- FUNCTION: Catalyzes the reaction that attaches fucose through an O- CC glycosidic linkage to a conserved serine or threonine residue found in CC the consensus sequence C2-X(4,5)-[S/T]-C3 of EGF domains, where C2 and CC C3 are the second and third conserved cysteines (PubMed:12909620). CC Specifically uses GDP-fucose as donor substrate and proper disulfide CC pairing of the substrate EGF domains is required for fucose transfer CC (By similarity). Plays a crucial role in Notch signaling CC (PubMed:12917292, PubMed:12909620, PubMed:17329366). Initial CC fucosylation of Notch/N by O-fut1 generates a substrate for Fringe/Fng, CC an acetylglucosaminyltransferase that can then extend the fucosylation CC on the Notch EGF repeats (PubMed:12909620). This extended fucosylation CC is required for optimal ligand binding and canonical NOTCH signaling CC induced by Delta/Dl or Serrate/Ser (PubMed:12909620, PubMed:12917292). CC Also required for the transport of Notch/N to the early endosome CC (PubMed:17329366). {ECO:0000250|UniProtKB:Q9H488, CC ECO:0000269|PubMed:12909620, ECO:0000269|PubMed:12917292, CC ECO:0000269|PubMed:17329366}. CC -!- CATALYTIC ACTIVITY: CC Reaction=GDP-beta-L-fucose + L-seryl-[protein] = 3-O-(alpha-L-fucosyl)- CC L-seryl-[protein] + GDP + H(+); Xref=Rhea:RHEA:63644, Rhea:RHEA- CC COMP:9863, Rhea:RHEA-COMP:17914, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:29999, ChEBI:CHEBI:57273, ChEBI:CHEBI:58189, CC ChEBI:CHEBI:189632; EC=2.4.1.221; CC Evidence={ECO:0000269|PubMed:12909620}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63645; CC Evidence={ECO:0000269|PubMed:12909620}; CC -!- CATALYTIC ACTIVITY: CC Reaction=GDP-beta-L-fucose + L-threonyl-[protein] = 3-O-(alpha-L- CC fucosyl)-L-threonyl-[protein] + GDP + H(+); Xref=Rhea:RHEA:70491, CC Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:17915, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:30013, ChEBI:CHEBI:57273, ChEBI:CHEBI:58189, CC ChEBI:CHEBI:189631; EC=2.4.1.221; CC Evidence={ECO:0000269|PubMed:12909620}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70492; CC Evidence={ECO:0000269|PubMed:12909620}; CC -!- PATHWAY: Protein modification; protein glycosylation. CC {ECO:0000269|PubMed:12909620}. CC -!- SUBUNIT: Interacts with N (via its EGF domains); the interaction is CC required for the endocyctic transport of N. CC {ECO:0000269|PubMed:17329366}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum CC {ECO:0000250|UniProtKB:Q6EV70}. CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically. CC {ECO:0000269|PubMed:12917292}. CC -!- SIMILARITY: Belongs to the glycosyltransferase 65 family. CC {ECO:0000305}. CC -!- SEQUENCE CAUTION: CC Sequence=AAM50020.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; 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; AB093572; BAC55010.1; -; mRNA. DR EMBL; AE013599; AAF58290.1; -; Genomic_DNA. DR EMBL; BT021295; AAX33443.1; -; mRNA. DR EMBL; AY118651; AAM50020.1; ALT_INIT; mRNA. DR RefSeq; NP_001286406.1; NM_001299477.1. DR RefSeq; NP_610931.1; NM_137087.3. DR AlphaFoldDB; Q9V6X7; -. DR SMR; Q9V6X7; -. DR BioGRID; 62315; 9. DR DIP; DIP-20580N; -. DR IntAct; Q9V6X7; 2. DR STRING; 7227.FBpp0308981; -. DR CAZy; GT65; Glycosyltransferase Family 65. DR GlyCosmos; Q9V6X7; 1 site, No reported glycans. DR GlyGen; Q9V6X7; 1 site. DR PaxDb; 7227-FBpp0086649; -. DR DNASU; 36564; -. DR EnsemblMetazoa; FBtr0087520; FBpp0086649; FBgn0033901. DR EnsemblMetazoa; FBtr0339959; FBpp0308981; FBgn0033901. DR GeneID; 36564; -. DR KEGG; dme:Dmel_CG12366; -. DR AGR; FB:FBgn0033901; -. DR CTD; 36564; -. DR FlyBase; FBgn0033901; O-fut1. DR VEuPathDB; VectorBase:FBgn0033901; -. DR eggNOG; KOG3849; Eukaryota. DR GeneTree; ENSGT00390000015634; -. DR HOGENOM; CLU_039551_0_0_1; -. DR InParanoid; Q9V6X7; -. DR OMA; KWQAKYP; -. DR OrthoDB; 5384121at2759; -. DR PhylomeDB; Q9V6X7; -. DR BRENDA; 2.4.1.221; 1994. DR SignaLink; Q9V6X7; -. DR UniPathway; UPA00378; -. DR BioGRID-ORCS; 36564; 0 hits in 1 CRISPR screen. DR GenomeRNAi; 36564; -. DR PRO; PR:Q9V6X7; -. DR Proteomes; UP000000803; Chromosome 2R. DR Bgee; FBgn0033901; Expressed in eye disc (Drosophila) and 20 other cell types or tissues. DR ExpressionAtlas; Q9V6X7; baseline and differential. DR GO; GO:0005783; C:endoplasmic reticulum; IDA:FlyBase. DR GO; GO:0008417; F:fucosyltransferase activity; ISS:UniProtKB. DR GO; GO:0005112; F:Notch binding; IDA:FlyBase. DR GO; GO:0046922; F:peptide-O-fucosyltransferase activity; IDA:FlyBase. DR GO; GO:0045165; P:cell fate commitment; IMP:FlyBase. DR GO; GO:0006004; P:fucose metabolic process; IEA:UniProtKB-KW. DR GO; GO:0007219; P:Notch signaling pathway; NAS:UniProtKB. DR GO; GO:0016266; P:O-glycan processing; TAS:UniProtKB. DR GO; GO:0045807; P:positive regulation of endocytosis; IMP:FlyBase. DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IMP:FlyBase. DR GO; GO:0006493; P:protein O-linked glycosylation; ISS:UniProtKB. DR CDD; cd11302; O-FucT-1; 1. DR Gene3D; 3.40.50.11340; -; 1. DR Gene3D; 3.40.50.11350; -; 1. DR InterPro; IPR019378; GDP-Fuc_O-FucTrfase. DR InterPro; IPR039922; POFUT1. DR PANTHER; PTHR21420; GDP-FUCOSE PROTEIN O-FUCOSYLTRANSFERASE 1; 1. DR PANTHER; PTHR21420:SF10; GDP-FUCOSE PROTEIN O-FUCOSYLTRANSFERASE 1; 1. DR Pfam; PF10250; O-FucT; 1. DR Genevisible; Q9V6X7; DM. PE 1: Evidence at protein level; KW Carbohydrate metabolism; Disulfide bond; Endoplasmic reticulum; KW Fucose metabolism; Glycoprotein; Glycosyltransferase; KW Notch signaling pathway; Reference proteome; Signal; Transferase. FT SIGNAL 1..23 FT /evidence="ECO:0000255" FT CHAIN 24..402 FT /note="GDP-fucose protein O-fucosyltransferase 1" FT /id="PRO_0000012153" FT BINDING 41..44 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9H488" FT BINDING 243..245 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9H488" FT BINDING 349 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9H488" FT BINDING 366..367 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9H488" FT CARBOHYD 60 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 36..38 FT /evidence="ECO:0000250|UniProtKB:Q9H488" FT DISULFID 122..141 FT /evidence="ECO:0000250|UniProtKB:Q9H488" FT DISULFID 254..284 FT /evidence="ECO:0000250|UniProtKB:Q9H488" FT DISULFID 269..363 FT /evidence="ECO:0000250|UniProtKB:Q9H488" FT CONFLICT 371 FT /note="E -> V (in Ref. 5; AAM50020)" FT /evidence="ECO:0000305" FT CONFLICT 389 FT /note="K -> E (in Ref. 1; BAC55010 and 4; AAX33443)" FT /evidence="ECO:0000305" SQ SEQUENCE 402 AA; 46834 MW; E52FF4F86509C2E6 CRC64; MQWLKMKLRF VNLILLLISS TCAQLGGDPN GYLTYCPCMG RFGNQADHFL GSLAFAKALN RTLILPPWVE YRRGELRSRQ VPFNTYFEVE PLKEYHRVIT MADFMWHLAD DIWPESERVS FCYKERYSLQ QEKNDPDKPN CHAKDGNPFG PFWDTFHIDF VRSEFYAPLH FDVHHSNEAA KWQTKYPAES YPVLAFTGAP ASFPVQLENC KLQRYLQWSQ RYREASKDFI REQLPRGAFL GIHLRNGIDW VRACEHVKDS QHLFASPQCL GYKNERGALY PELCMPSKEA IIRQLKRTIK NVRQTQPDNE IKSVFVASDS NHMIGELNTA LSRMGISVHK LPEDDPYLDL AILGQSNHFI GNCISSYSAF EKRERDVHGF PSYFWGFPKE KDRKHTNVHE EL //