OFUT1_DROME
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 03-AUG-2022, entry version 153.
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.FBpp0086649; -.
DR CAZy; GT65; Glycosyltransferase Family 65.
DR GlyGen; Q9V6X7; 1 site.
DR PaxDb; Q9V6X7; -.
DR PRIDE; Q9V6X7; -.
DR DNASU; 36564; -.
DR EnsemblMetazoa; FBtr0087520; FBpp0086649; FBgn0033901.
DR EnsemblMetazoa; FBtr0339959; FBpp0308981; FBgn0033901.
DR GeneID; 36564; -.
DR KEGG; dme:Dmel_CG12366; -.
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; YPELCMP; -.
DR OrthoDB; 1127619at2759; -.
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 tissues.
DR ExpressionAtlas; Q9V6X7; baseline and differential.
DR Genevisible; Q9V6X7; DM.
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:0036066; P:protein O-linked fucosylation; IBA:GO_Central.
DR GO; GO:0006493; P:protein O-linked glycosylation; ISS:UniProtKB.
DR GO; GO:0008593; P:regulation of Notch signaling pathway; IBA:GO_Central.
DR CDD; cd11302; O-FucT-1; 1.
DR InterPro; IPR019378; GDP-Fuc_O-FucTrfase.
DR InterPro; IPR039922; POFUT1.
DR PANTHER; PTHR21420; PTHR21420; 1.
DR Pfam; PF10250; O-FucT; 1.
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
