OFUT1_CRIGR
ID OFUT1_CRIGR Reviewed; 392 AA.
AC P83337; G3HE95;
DT 13-SEP-2004, integrated into UniProtKB/Swiss-Prot.
DT 09-JAN-2013, sequence version 2.
DT 03-AUG-2022, entry version 76.
DE RecName: Full=GDP-fucose protein O-fucosyltransferase 1;
DE EC=2.4.1.221 {ECO:0000269|PubMed:8358148, ECO:0000269|PubMed:9023546, ECO:0000269|PubMed:9525914};
DE AltName: Full=Peptide-O-fucosyltransferase 1;
DE Short=O-FucT-1;
GN Name=POFUT1;
OS Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=21804562; DOI=10.1038/nbt.1932;
RA Xu X., Nagarajan H., Lewis N.E., Pan S., Cai Z., Liu X., Chen W., Xie M.,
RA Wang W., Hammond S., Andersen M.R., Neff N., Passarelli B., Koh W.,
RA Fan H.C., Wang J., Gui Y., Lee K.H., Betenbaugh M.J., Quake S.R.,
RA Famili I., Palsson B.O., Wang J.;
RT "The genomic sequence of the Chinese hamster ovary (CHO)-K1 cell line.";
RL Nat. Biotechnol. 29:735-741(2011).
RN [2] {ECO:0000305}
RP PROTEIN SEQUENCE OF 28-88.
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 [3] {ECO:0000305}
RP ACTIVITY REGULATION, SUBSTRATE SPECIFICITY, AND CATALYTIC ACTIVITY.
RX PubMed=8358148; DOI=10.1093/glycob/3.3.219;
RA Harris R.J., Spellman M.W.;
RT "O-linked fucose and other post-translational modifications unique to EGF
RT modules.";
RL Glycobiology 3:219-224(1993).
RN [4] {ECO:0000305}
RP FUNCTION, AND CATALYTIC ACTIVITY.
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 [5] {ECO:0000305}
RP BIOPHYSICOCHEMICAL PROPERTIES, SUBSTRATE SPECIFICITY, GLYCOSYLATION, AND
RP STRUCTURE OF CARBOHYDRATES.
RX PubMed=9525914; DOI=10.1074/jbc.273.14.8112;
RA Wang Y., Spellman M.W.;
RT "Purification and characterization of a GDP-fucose:polypeptide
RT fucosyltransferase from Chinese hamster ovary cells.";
RL J. Biol. Chem. 273:8112-8118(1998).
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. Plays a crucial role in
CC NOTCH signaling. Initial fucosylation of NOTCH by POFUT1 generates a
CC substrate for FRINGE/RFNG, an acetylglucosaminyltransferase that can
CC then extend the fucosylation on the NOTCH EGF repeats. This extended
CC fucosylation is required for optimal ligand binding and canonical NOTCH
CC signaling induced by DELTA1 or JAGGED1 (By similarity). Fucosylates
CC AGRN and determines its ability to cluster acetylcholine receptors
CC (AChRs) (By similarity). {ECO:0000250, 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:8358148, ECO:0000269|PubMed:9023546,
CC ECO:0000269|PubMed:9525914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63645;
CC Evidence={ECO:0000269|PubMed:8358148, ECO:0000269|PubMed:9023546,
CC ECO:0000269|PubMed:9525914};
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:8358148, ECO:0000269|PubMed:9023546,
CC ECO:0000269|PubMed:9525914};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70492;
CC Evidence={ECO:0000269|PubMed:8358148, ECO:0000269|PubMed:9023546,
CC ECO:0000269|PubMed:9525914};
CC -!- ACTIVITY REGULATION: Activated by manganese and, to a lesser extent, by
CC other divalent metals such as cobalt and calcium. Inhibited by copper,
CC ferric and zinc ions. {ECO:0000269|PubMed:8358148}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=11 uM for His(6)-F7-EGF-1 {ECO:0000269|PubMed:9525914};
CC KM=15 uM for F7-EGF-1 {ECO:0000269|PubMed:9525914};
CC Vmax=2.5 umol/min/mg enzyme {ECO:0000269|PubMed:9525914};
CC Vmax=2.4 umol/min/mg enzyme {ECO:0000269|PubMed:9525914};
CC pH dependence:
CC Optimum pH is 5.5-8.0. {ECO:0000269|PubMed:9525914};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000250|UniProtKB:Q6EV70}.
CC -!- PTM: N-glycosylated. Contains high mannose-type carbohydrates.
CC {ECO:0000269|PubMed:9525914}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 65 family.
CC {ECO:0000305}.
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DR EMBL; JH000311; EGW00282.1; -; Genomic_DNA.
DR RefSeq; XP_003502364.1; XM_003502316.2.
DR AlphaFoldDB; P83337; -.
DR SMR; P83337; -.
DR STRING; 10029.XP_007618809.1; -.
DR Ensembl; ENSCGRT00001015791; ENSCGRP00001011559; ENSCGRG00001013152.
DR GeneID; 100753417; -.
DR KEGG; cge:100753417; -.
DR CTD; 23509; -.
DR eggNOG; KOG3849; Eukaryota.
DR GeneTree; ENSGT00390000015634; -.
DR InParanoid; P83337; -.
DR OMA; YPELCMP; -.
DR OrthoDB; 1127619at2759; -.
DR UniPathway; UPA00378; -.
DR Proteomes; UP000001075; Unassembled WGS sequence.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016757; F:glycosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0046922; F:peptide-O-fucosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0016740; F:transferase activity; IDA:UniProtKB.
DR GO; GO:0001525; P:angiogenesis; IEA:Ensembl.
DR GO; GO:0006004; P:fucose metabolic process; IEA:UniProtKB-KW.
DR GO; GO:0007507; P:heart development; IEA:Ensembl.
DR GO; GO:0007399; P:nervous system development; IEA:Ensembl.
DR GO; GO:0007219; P:Notch signaling pathway; IEA:UniProtKB-KW.
DR GO; GO:0006486; P:protein glycosylation; IDA:UniProtKB.
DR GO; GO:0008593; P:regulation of Notch signaling pathway; ISS:UniProtKB.
DR GO; GO:0001756; P:somitogenesis; IEA:Ensembl.
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; Direct protein sequencing; Disulfide bond;
KW Endoplasmic reticulum; Fucose metabolism; Glycoprotein;
KW Glycosyltransferase; Notch signaling pathway; Reference proteome;
KW Transferase.
FT CHAIN 1..392
FT /note="GDP-fucose protein O-fucosyltransferase 1"
FT /id="PRO_0000220935"
FT MOTIF 389..392
FT /note="Prevents secretion from ER"
FT /evidence="ECO:0000255"
FT BINDING 47..50
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9H488"
FT BINDING 242..244
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9H488"
FT BINDING 344
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9H488"
FT BINDING 361..362
FT /ligand="substrate"
FT /evidence="ECO:0000250|UniProtKB:Q9H488"
FT CARBOHYD 66
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 164
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 42..44
FT /evidence="ECO:0000250|UniProtKB:Q9H488"
FT DISULFID 130..144
FT /evidence="ECO:0000250|UniProtKB:Q9H488"
FT DISULFID 253..287
FT /evidence="ECO:0000250|UniProtKB:Q9H488"
FT DISULFID 271..358
FT /evidence="ECO:0000250|UniProtKB:Q9H488"
FT CONFLICT 66
FT /note="N -> V (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 392 AA; 44669 MW; 45E1421CBA0880C4 CRC64;
MGAAAWAPPH LLLRVSLLLL LLLPLRGRLA GSWDLAGYLL YCPCMGRFGN QADHFLGSLA
FAKLLNRTLA VPPWIEYQHH KPPFTNLHVS YQKYFKLEPL QAYHRVISLE EFMEKLAPIH
WPPEKRVAYC FEVAAQRSPD KKTCPMKEGN PFGPFWDQFH VSFNKSELFT GISFSASYKE
QWIQRFPPEE HPVLALPGAP AQFPVLEEHR ALQKYMVWSD EMVKTGEAQI STHLIRPYVG
IHLRIGSDWK NACAMLKDGT AGSHFMASPQ CVGYSRSTAT PLTMTMCLPD LNEIQRAVKL
WVRALNARSI YIATDSESYV PEIQQLFKEK VKVVSLKPEV AQVDLYILGQ ADHFIGNCVS
SFTAFVKRER DLHGRQSSFF GMDRPSQPRD EF
