ID   OFUT1_RAT               Reviewed;         395 AA.
AC   Q6EV70;
DT   01-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT   16-AUG-2004, sequence version 1.
DT   24-JAN-2024, entry version 108.
DE   RecName: Full=GDP-fucose protein O-fucosyltransferase 1;
DE            EC=2.4.1.221 {ECO:0000269|PubMed:9023546};
DE   AltName: Full=Peptide-O-fucosyltransferase 1;
DE            Short=O-FucT-1;
DE   Flags: Precursor;
GN   Name=Pofut1 {ECO:0000312|RGD:1303001}; Synonyms=Fut12;
OS   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1] {ECO:0000312|EMBL:CAH03711.1}
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Wistar {ECO:0000312|EMBL:CAH03711.1};
RX   PubMed=12966037; DOI=10.1093/glycob/cwg113;
RA   Martinez-Duncker I., Mollicone R., Candelier J.-J., Breton C., Oriol R.;
RT   "A new superfamily of protein-O-fucosyltransferases, alpha2-
RT   fucosyltransferases, and alpha6-fucosyltransferases: phylogeny and
RT   identification of conserved peptide motifs.";
RL   Glycobiology 13:1C-5C(2003).
RN   [2]
RP   CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBSTRATE SPECIFICITY, AND
RP   PATHWAY.
RX   PubMed=9023546; DOI=10.1093/glycob/6.8.837;
RA   Wang Y., Lee G.F., Kelley R.F., Spellman M.W.;
RT   "Identification of a GDP-L-fucose:polypeptide fucosyltransferase and
RT   enzymatic addition of O-linked fucose to EGF domains.";
RL   Glycobiology 6:837-842(1996).
RN   [3] {ECO:0000305}
RP   FUNCTION, SUBCELLULAR LOCATION, AND PATHWAY.
RX   PubMed=15653671; DOI=10.1074/jbc.m414574200;
RA   Luo Y., Haltiwanger R.S.;
RT   "O-fucosylation of notch occurs in the endoplasmic reticulum.";
RL   J. Biol. Chem. 280:11289-11294(2005).
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. Specifically uses GDP-
CC       fucose as donor substrate and proper disulfide pairing of the substrate
CC       EGF domains is required for fucose transfer. Fucosylates AGRN and
CC       determines its ability to cluster acetylcholine receptors (AChRs) (By
CC       similarity). Plays a crucial role in NOTCH signaling. Initial
CC       fucosylation of NOTCH by POFUT1 generates a substrate for FRINGE/RFNG,
CC       an acetylglucosaminyltransferase that can then extend the fucosylation
CC       on the NOTCH EGF repeats. This extended fucosylation is required for
CC       optimal ligand binding and canonical NOTCH signaling induced by DLL1 or
CC       JAGGED1. {ECO:0000250, ECO:0000269|PubMed:15653671,
CC       ECO:0000269|PubMed:9023546}.
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:9023546};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63645;
CC         Evidence={ECO:0000269|PubMed:9023546};
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:9023546};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70492;
CC         Evidence={ECO:0000269|PubMed:9023546};
CC   -!- ACTIVITY REGULATION: Activated by manganese and, to a lesser extent, by
CC       calcium. {ECO:0000269|PubMed:9023546}.
CC   -!- PATHWAY: Protein modification; protein glycosylation.
CC       {ECO:0000269|PubMed:15653671, ECO:0000269|PubMed:9023546}.
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC       {ECO:0000269|PubMed:15653671}.
CC   -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P83337}.
CC   -!- SIMILARITY: Belongs to the glycosyltransferase 65 family.
CC       {ECO:0000255}.
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DR   EMBL; AJ781499; CAH03711.1; -; mRNA.
DR   RefSeq; NP_001002278.1; NM_001002278.1.
DR   AlphaFoldDB; Q6EV70; -.
DR   SMR; Q6EV70; -.
DR   STRING; 10116.ENSRNOP00000013730; -.
DR   CAZy; GT65; Glycosyltransferase Family 65.
DR   GlyCosmos; Q6EV70; 2 sites, No reported glycans.
DR   GlyGen; Q6EV70; 2 sites.
DR   PhosphoSitePlus; Q6EV70; -.
DR   jPOST; Q6EV70; -.
DR   PaxDb; 10116-ENSRNOP00000013730; -.
DR   Ensembl; ENSRNOT00000013730.4; ENSRNOP00000013730.1; ENSRNOG00000010104.4.
DR   Ensembl; ENSRNOT00055043029; ENSRNOP00055035117; ENSRNOG00055024966.
DR   Ensembl; ENSRNOT00060035198; ENSRNOP00060028940; ENSRNOG00060020299.
DR   Ensembl; ENSRNOT00065042065; ENSRNOP00065034392; ENSRNOG00065024520.
DR   GeneID; 311551; -.
DR   KEGG; rno:311551; -.
DR   UCSC; RGD:1303001; rat.
DR   AGR; RGD:1303001; -.
DR   CTD; 23509; -.
DR   RGD; 1303001; Pofut1.
DR   eggNOG; KOG3849; Eukaryota.
DR   GeneTree; ENSGT00390000015634; -.
DR   HOGENOM; CLU_039551_0_0_1; -.
DR   InParanoid; Q6EV70; -.
DR   OMA; QRFPPKE; -.
DR   OrthoDB; 5384121at2759; -.
DR   PhylomeDB; Q6EV70; -.
DR   TreeFam; TF314805; -.
DR   UniPathway; UPA00378; -.
DR   PRO; PR:Q6EV70; -.
DR   Proteomes; UP000002494; Chromosome 3.
DR   Bgee; ENSRNOG00000010104; Expressed in liver and 19 other cell types or tissues.
DR   GO; GO:0005783; C:endoplasmic reticulum; ISO:RGD.
DR   GO; GO:0016020; C:membrane; ISS:UniProtKB.
DR   GO; GO:0008417; F:fucosyltransferase activity; ISS:UniProtKB.
DR   GO; GO:0046922; F:peptide-O-fucosyltransferase activity; ISO:RGD.
DR   GO; GO:0001525; P:angiogenesis; ISO:RGD.
DR   GO; GO:0006004; P:fucose metabolic process; IEA:UniProtKB-KW.
DR   GO; GO:0007507; P:heart development; ISO:RGD.
DR   GO; GO:0007399; P:nervous system development; ISO:RGD.
DR   GO; GO:0007219; P:Notch signaling pathway; ISO:RGD.
DR   GO; GO:0036066; P:protein O-linked fucosylation; ISO:RGD.
DR   GO; GO:0006493; P:protein O-linked glycosylation; ISS:UniProtKB.
DR   GO; GO:0008593; P:regulation of Notch signaling pathway; ISS:UniProtKB.
DR   GO; GO:0001756; P:somitogenesis; ISO:RGD.
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:SF3; GDP-FUCOSE PROTEIN O-FUCOSYLTRANSFERASE 1; 1.
DR   Pfam; PF10250; O-FucT; 1.
DR   Genevisible; Q6EV70; RN.
PE   1: Evidence at protein level;
KW   Carbohydrate metabolism; Disulfide bond; Endoplasmic reticulum;
KW   Fucose metabolism; Glycoprotein; Glycosyltransferase; Manganese;
KW   Notch signaling pathway; Reference proteome; Signal; Transferase.
FT   SIGNAL          1..32
FT                   /evidence="ECO:0000255"
FT   CHAIN           33..395
FT                   /note="GDP-fucose protein O-fucosyltransferase 1"
FT                   /evidence="ECO:0000255"
FT                   /id="PRO_0000012151"
FT   MOTIF           392..395
FT                   /note="Prevents secretion from ER"
FT   BINDING         50..53
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H488"
FT   BINDING         245..247
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H488"
FT   BINDING         347
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H488"
FT   BINDING         364..365
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:Q9H488"
FT   CARBOHYD        69
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        167
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        45..47
FT                   /evidence="ECO:0000250|UniProtKB:Q9H488"
FT   DISULFID        133..147
FT                   /evidence="ECO:0000250|UniProtKB:Q9H488"
FT   DISULFID        256..290
FT                   /evidence="ECO:0000250|UniProtKB:Q9H488"
FT   DISULFID        274..361
FT                   /evidence="ECO:0000250|UniProtKB:Q9H488"
SQ   SEQUENCE   395 AA;  44983 MW;  2A85521E22F38920 CRC64;
     MGAAAWAPSH LLLRASFLLL LLLLPLPLRG RAGGSWDLAG YLLYCPCMGR FGNQADHFLG
     SLAFAKLLNR TLAVPPWIEY QHHKPPFTNL HVSYQKYFKL EPLQAYHRVI SLEDFMEKLA
     PFHWPPEKRV AYCFEVAAQR SPDKKTCPMK EGNPFGPFWD QFHVSFNKSE LFTGISFSAS
     YKEQWIQRFP PKEHPVLALP GAPAQFPVLE EHRELQKYMV WSDEMVRTGE AQISTHLVRP
     YVGIHLRIGS DWKNACAMLK DGTAGSHFMA SPQCVGYSRS TATPLTTTMC LPDLKEIQRA
     VKLWVRALDA RSVYIATDSE SYVSEIQQLF KEKVKVVSLK PEVAQIDLYI LGQADHFIGN
     CVSSFTAFVK RERDLHGRPS SFFGMDRPSQ LRDEF
//