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Information on EC 2.4.1.221 - peptide-O-fucosyltransferase and Organism(s) Homo sapiens and UniProt Accession Q9Y2G5
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EC Tree
2.4.1.221 peptide-O-fucosyltransferaseIUBMB Comments
The enzyme, found in animals and plants, is involved in the biosynthesis of O-fucosylated proteins. In EGF domains, the attachment of O-linked fucose to serine or threonine occurs within the sequence Cys-Xaa-Xaa-Gly-Gly-Ser/Thr-Cys.
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Word Map
- 2.4.1.221
- notch
-
o-fucosylation
-
o-fucose
-
factor-like
-
o-linked
- thrombospondin
-
fringe
-
dowling-degos
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egf-like
- poglut1
-
notch-ligand
-
lunatic
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plagl2
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somitogenesis
- dll1
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genodermatosis
- hidradenitis
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o-glucosyltransferase
- drug development
- medicine
- molecular biology
- diagnostics
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria
Reaction Schemes
+
=
+
+
[protein]-(L-serine/L-threonine)
=
+
[protein]-3-O-(alpha-L-fucosyl)-(L-serine/L-threonine)
Synonyms
pofut1, protein o-fucosyltransferase 1, pofut2, o-fucosyltransferase, ofut1, protein o-fucosyltransferase 2, o-fut1, o-fuct-1, alpha-6-fucosyltransferase, o-fucosyltransferase 1, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
alpha-6-fucosyltransferase
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core alpha6FucT
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fucosyltransferase, guanosine diphosphofucose-glycoprotein
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GDP-fucose glycoprotein fucosyltransferase
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GDP-fucose protein O-fucosyltransferase
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GDP-fucose:polypeptide fucosyltransferase
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GDP-L-fucose-glycoprotein fucosyltransferase
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GDP-L-fucose:polypeptide fucosyltransferase
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glycoprotein fucosyltransferase
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guanosine diphosphofucose-glycoprotein fucosyltransferase
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N-acetyl-beta-D-glucosaminide alpha1-->6-fucosyltransferase
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N-glycan alpha-6-fucosyltransferase
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O-fucT-1
Pofut1
POFUT2
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O-fucT-1
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Pofut1
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REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
GDP-beta-L-fucose + [protein]-(L-serine/L-threonine) = GDP + [protein]-3-O-(alpha-L-fucosyl)-(L-serine/L-threonine)
catalytic mechanism and substrate specificity, overview
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
glycosyl group transfer
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-
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transglycosylation
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PATHWAY SOURCE
PATHWAYS
SYSTEMATIC NAME
IUBMB Comments
GDP-beta-L-fucose:protein-(L-serine/L-threonine) O-alpha-L-fucosyltransferase (configuration-inverting)
The enzyme, found in animals and plants, is involved in the biosynthesis of O-fucosylated proteins. In EGF domains, the attachment of O-linked fucose to serine or threonine occurs within the sequence Cys-Xaa-Xaa-Gly-Gly-Ser/Thr-Cys.
CAS REGISTRY NUMBER
COMMENTARY
9033-08-3
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SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
GDP-beta-L-fucose + protein
GDP + ?
protein O-fucosyltransferases 1 and 2 (PoFUT1 and PoFUT2) are the enzymes responsible for this protein O-fucosylation and selectively glycosylate specific residues in epidermal growth factor-like (EGF) repeats and thrombospondin type I repeats (TSRs). PoFUT2 glycosylates thrombospondin type I repeats (TSRs) containing Ser/Thr residues located in the consensus sequences C1-X-X-S/T-C2 or C2-X-X-S/T-C3 of TSRs of groups 1 and 2
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-
?
GDP-beta-L-fucose + protein
GDP + ?
SN2-like mechanism. PoFUT2 glycosylates thrombospondin type I repeats (TSRs) containing Ser/Thr residues located in the consensus sequences C1-X-X-S/T-C2 or C2-X-X-S/T-C3 of TSRs of groups 1 and 2
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-
?
GDP-fucose + TSR4
GDP + fucosyl-TSR4
GDP-fucose binding mode, overview. Activity with recombinant TSR4 mutants expressed in HEK293Tcells
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-
?
GDP-beta-L-fucose + protein
GDP + ?
protein O-fucosyltransferases 1 and 2 (PoFUT1 and PoFUT2) are the enzymes responsible for this protein O-fucosylation and selectively glycosylate specific residues in epidermal growth factor-like (EGF) repeats and thrombospondin type I repeats (TSRs). PoFUT1 glycosylates epidermal growth factor-like (EGF) repeats within the consensus sequence C2-X-X-X-X-S/T-C3
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-
?
GDP-beta-L-fucose + protein
GDP + ?
SN1-like mechanism. PoFUT1 glycosylates epidermal growth factor-like (EGF) repeats within the consensus sequence C2-X-X-X-X-S/T-C3
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?
additional information
?
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fucose is added exclusively to properly folded Epidermal Growth Factor-like (EGF) repeats and Thrombospondin Type 1 Repeats (TSRs)
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additional information
?
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fucose is added exclusively to properly folded Epidermal Growth Factor-like (EGF) repeats and Thrombospondin Type 1 Repeats (TSRs)
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additional information
?
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O-fucosylation of thrombospondin-1 at Ser 377, Thr 432 and Thr 489
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?
additional information
?
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adds o-fucose to epidermal growth factor-like repeats
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?
additional information
?
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adds o-fucose to epidermal growth factor-like repeats
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?
additional information
?
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may be involved in intracellular quality control
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?
additional information
?
-
the enzyme catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch
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?
additional information
?
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the enzyme catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch
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?
additional information
?
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fucose is added exclusively to properly folded Epidermal Growth Factor-like (EGF) repeats and Thrombospondin Type 1 Repeats (TSRs). The O-linked fucose can also be elongated with other sugars
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additional information
?
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fucose is added exclusively to properly folded Epidermal Growth Factor-like (EGF) repeats and Thrombospondin Type 1 Repeats (TSRs). The O-linked fucose can also be elongated with other sugars
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NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
GDP-beta-L-fucose + protein
GDP + ?
protein O-fucosyltransferases 1 and 2 (PoFUT1 and PoFUT2) are the enzymes responsible for this protein O-fucosylation and selectively glycosylate specific residues in epidermal growth factor-like (EGF) repeats and thrombospondin type I repeats (TSRs). PoFUT2 glycosylates thrombospondin type I repeats (TSRs) containing Ser/Thr residues located in the consensus sequences C1-X-X-S/T-C2 or C2-X-X-S/T-C3 of TSRs of groups 1 and 2
-
-
?
GDP-beta-L-fucose + protein
GDP + ?
protein O-fucosyltransferases 1 and 2 (PoFUT1 and PoFUT2) are the enzymes responsible for this protein O-fucosylation and selectively glycosylate specific residues in epidermal growth factor-like (EGF) repeats and thrombospondin type I repeats (TSRs). PoFUT1 glycosylates epidermal growth factor-like (EGF) repeats within the consensus sequence C2-X-X-X-X-S/T-C3
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?
additional information
?
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may be involved in intracellular quality control
-
-
?
additional information
?
-
the enzyme catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch
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-
?
additional information
?
-
-
the enzyme catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch
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-
?
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
additional information
steady-state kinetic measurements of wild-type and mutant POFUT2
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additional information
additional information
-
steady-state kinetic measurements of wild-type and mutant POFUT2
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TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
upregulated in esophageal cancer stem-like cell in comparison to adherent cells
upregulated in esophageal cancer stem-like cell in comparison to adherent cells
analysis of enzyme expression in 8 HCC cell lines and 253 human HCC tissues, overview
oral squamous cell carcinoma cell-derived cell lines and primary oral squamous cell carcinoma cells, increased enzyme expression
additional information
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
evolution
POFUT2 belongs to the classical GT-B fold family of glycosyltransferases with two closely interacting Rossmann-like domains. POFUT2 shows a variation of the classical GT-B fold
physiological function
malfunction
physiological function
additional information
physiological function
protein O-fucosyltransferase 2 catalyzes the protein O-fucosylation, a post-translational modification found on serine/threonine residues of thrombospondin type 1 repeats
physiological function
both POFUT1 and POFUT2 participate in non-canonical endoplasmic reticulum quality control pathways for the folding of Epidermal Growth Factor-like (EGF) repeats and Thrombospondin Type 1 Repeats (TSRs), respectively
physiological function
protein O-fucosyltransferases 1 and 2 (PoFUT1 and PoFUT2) are the enzymes responsible for this protein O-fucosylation and selectively glycosylate specific residues in epidermal growth factor-like (EGF) repeats and thrombospondin type I repeats (TSRs). PoFUT2 glycosylates thrombospondin type I repeats (TSRs) containing Ser/Thr residues located in the consensus sequences C1-X-X-S/T-C2 or C2-X-X-S/T-C3 of TSRs of groups 1 and 2
malfunction
cell proliferation of POFUT1 knockdown cells is significantly inhibited compared with that of control cells, phenotypes, overview
malfunction
knockdown and overexpression of Pofut1 inhibits and accelerates the growth, migration and invasion of hepatocellular carcinoma cells, respectively
malfunction
CRISPR-mediated knockout of POFUT1 in U2OS cells suppresses both normal Notch1 signaling, and the ligand-independent signaling associated with leukemogenic mutations of Notch1. Normal and oncogenic signaling are rescued by wild-type POFUT1 but rescue is impaired by an active-site R240A mutation
malfunction
heterozygous mutations in POFUT1 are linked to a rare skin condition, Dowling-Degos Disease. Amplification of POFUT1 is associated with several types of cancer
physiological function
the enzyme adds O-fucose through O-glycosidic linkage to conserved serine or threonine residues in the epidermal growth factor-like repeats of a number of cellular surface and secreted proteins. ENzyme POFUT1 expression can contribute to cancer progression
physiological function
the enzyme catalyzes the addition of O-linked fucose to the epidermal growth factor-like repeats of Notch. Pofut1 overexpression accelerates cell proliferation and migration in hepatocellular carcinoma cells and it promotes the binding of Notch ligand Dll1 to Notch receptor, and hence activates Notch signaling pathway in hepatocellular carcinoma cells
physiological function
both POFUT1 and POFUT2 are proposed to participate in non-canonical endoplasmic reticulum quality control pathways for the folding of Epidermal Growth Factor-like (EGF) repeats and Thrombospondin Type 1 Repeats (TSRs), respectively
physiological function
protein O-fucosylation is an important glycosylation modification and plays an important role in embryonic development. Protein O-fucosyltransferase 1 promotes trophoblast cell proliferation through activation of MAPK and PI3K/Akt signaling pathways
physiological function
protein O-fucosyltransferases 1 and 2 (PoFUT1 and PoFUT2) are the enzymes responsible for this protein O-fucosylation and selectively glycosylate specific residues in epidermal growth factor-like (EGF) repeats and thrombospondin type I repeats (TSRs). PoFUT1 glycosylates epidermal growth factor-like (EGF) repeats within the consensus sequence C2-X-X-X-X-S/T-C3
additional information
recognition of a small conserved 3D structural motif and mechanism of enzyme-protein substrate specificity. POFUT2 features a unique loop, residues 265-285, located on the opposite side of the large cleft, which protrudes from the C-terminal domain and which is attached to the N-terminal domain via a completely conserved tryptophan residue, W273 is involved in controlling movements of the N- and C-terminal domain relative to each other during the catalytic cycle, and 90% activity is lost in mutant W273A. Structure-function analysis of POFUT2 and comparison to POFUT1
additional information
-
recognition of a small conserved 3D structural motif and mechanism of enzyme-protein substrate specificity. POFUT2 features a unique loop, residues 265-285, located on the opposite side of the large cleft, which protrudes from the C-terminal domain and which is attached to the N-terminal domain via a completely conserved tryptophan residue, W273 is involved in controlling movements of the N- and C-terminal domain relative to each other during the catalytic cycle, and 90% activity is lost in mutant W273A. Structure-function analysis of POFUT2 and comparison to POFUT1
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). OFUT2_HUMAN
429
0
49976
Swiss-Prot
Secretory Pathway (Reliability: 1)
PDB
SCOP
CATH
UNIPROT
ORGANISM
POSTTRANSLATIONAL MODIFICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
contains a KDEL-like sequence at the C-terminus for retention in the endoplasmic reticulum
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
the crystal structure is reported in the free form and in the presence of GDP-fucose
vapor diffusion using the hanging drop method. Structures of the enzyme (POFUT1) in free and GDP-fucose bound states
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
D297A
site-directed mutagenesis, the mutant shows 15% activity compared to the wild-type enzyme
E396A
site-directed mutagenesis, the mutant shows 8% activity compared to the wild-type enzyme
W273a
site-directed mutagenesis, W273 is involved in controlling movements of the N- and C-terminal domain relative to each other during the catalytic cycle, and 90% activity is lost in mutant W273A
additional information
-
an artificial O-glycosylation pathway to produce an O-fucosylated epidermal growth factor (EGF) domain in Saccharomyces cerevisiae is generated. The in vivo O-fucosylation system is constructed via expression of genes that encode protein O-fut1 and the EGF domain, along with genes whose protein products convert cytoplasmic GDP-mannose to GDP-fucose
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
expression in tumorsphere is significantly higher than in parental adherent cells. Upregulated in esophageal cancer stem-like cell in comparison to adherent cells
expression in tumorsphere is significantly higher than in parental adherent cells. Upregulated in esophageal cancer stem-like cell in comparison to adherent cells
POFUT1 mRNA expression is upregulated in oral squamous cell carcinoma cells
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
diagnostics
drug development
POFUT1 is a potential target for cancers driven by Notch1 mutations
medicine
an aberrant activated Pofut1-Notch pathway is involved in hepatocellular carcinoma progression, and blockage of this pathway can be a promising strategy for the therapy of hepatocellular carcinomas
molecular biology
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engineering of an O-fucosylation system in yeast provides a powerful tool for producing proteins with homogenous carbohydrate chains. Such proteins can be used for the analysis of substrate specificity and the production of antibodies that recognize O-glycosylated EGF domains
diagnostics
enzyme POFUT1 may serve as a diagnostic marker and a therapeutic target for oral squamous cell carcinoma cells
diagnostics
Pofut1 overexpression clinically correlates with the unfavorable survival and high disease recurrence in hepatocellular carcinoma
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Hofsteenge, J.; Huwiler, K.G.; Bacik B.; Hess, D.; Lawler, J.; Mosher, D.F.; Peter-Katalinic, J.
C-mannosylation and o-fuxosylation of the thrombospondin type 1 module
J. Biol. Chem.
276
6485-6498
2001
Homo sapiens
ang, Y.; Shao, L.; Shi, S.; Harris, R.J.; Spellman, M.W.; Stanley, P.; Haltiwanger, R.S.
Modification of epidermal growth factor-like repeats with O-fucose. Molecular cloning and expression of a novel GDP-fucose protein O-fucosyltransferase
J. Biol. Chem.
276
40338-40345
2001
Candida elegans, Drosophila melanogaster, Homo sapiens (Q9H488), Homo sapiens, Mus musculus (Q91ZW2), Mus musculus
Luo, Y.; Haltiwanger, R.S.
O-fucosylation of notch occurs in the endoplasmic reticulum
J. Biol. Chem.
280
11289-11294
2005
Homo sapiens
Chigira, Y.; Oka, T.; Okajima, T.; Jigami, Y.
Engineering of a mammalian O-glycosylation pathway in the yeast Saccharomyces cerevisiae: production of O-fucosylated epidermal growth factor domains
Glycobiology
18
303-314
2008
Homo sapiens
Chen, C.I.; Keusch, J.J.; Klein, D.; Hess, D.; Hofsteenge, J.; Gut, H.
Structure of human POFUT2: insights into thrombospondin type 1 repeat fold and O-fucosylation
EMBO J.
31
3183-3197
2012
Homo sapiens (Q9Y2G5), Homo sapiens
Ma, L.; Dong, P.; Liu, L.; Gao, Q.; Duan, M.; Zhang, S.; Chen, S.; Xue, R.; Wang, X.
Overexpression of protein O-fucosyltransferase 1 accelerates hepatocellular carcinoma progression via the Notch signaling pathway
Biochem. Biophys. Res. Commun.
473
503-510
2016
Homo sapiens (Q9H488), Homo sapiens
Yokota, S.; Ogawara, K.; Kimura, R.; Shimizu, F.; Baba, T.; Minakawa, Y.; Higo, M.; Kasamatsu, A.; Endo-Sakamoto, Y.; Shiiba, M.; Tanzawa, H.; Uzawa, K.
Protein O-fucosyltransferase 1: a potential diagnostic marker and therapeutic target for human oral cancer
Int. J. Oncol.
43
1864-1870
2013
Homo sapiens (Q9H488), Homo sapiens
Lira-Navarrete, E.; Hurtado-Guerrero, R.
A perspective on structural and mechanistic aspects of protein O-fucosylation
Acta Crystallogr. Sect. F
74
443-450
2018
Caenorhabditis elegans (Q18014), Caenorhabditis elegans (Q8WR51), Mus musculus (Q91ZW2), Homo sapiens (Q9H488), Homo sapiens (Q9Y2G5)
Liu, C.; Liang, X.; Wang, J.; Zheng, Q.; Zhao, Y.; Khan, M.N.; Liu, S.; Yan, Q.
Protein O-fucosyltransferase 1 promotes trophoblast cell proliferation through activation of MAPK and PI3K/Akt signaling athways
Biomed. Pharmacother.
88
95-101
2017
Homo sapiens (Q9H488), Homo sapiens
Holdener, B.C.; Haltiwanger, R.S.
Protein O-fucosylation structure and function
Curr. Opin. Struct. Biol.
56
78-86
2019
Homo sapiens (Q9H488), Homo sapiens (Q9Y2G5)
Sanz, S.; Aquilini, E.; Tweedell, R.E.; Verma, G.; Hamerly, T.; Hritzo, B.; Tripathi, A.; Machado, M.; Churcher, T.S.; Rodrigues, J.A.; Izquierdo, L.; Dinglasan, R.R.
Protein O-fucosyltransferase 2 is not essential for Plasmodium berghei development
Front. Cell. Infect. Microbiol.
9
238
2019
Homo sapiens (Q9H488), Homo sapiens
McMillan, B.J.; Zimmerman, B.; Egan, E.D.; Lofgren, M.; Xu, X.; Hesser, A.; Blacklow, S.C.
Structure of human POFUT1, its requirement in ligand-independent oncogenic Notch signaling, and functional effects of Dowling-Degos mutations
Glycobiology
27
777-786
2017
Homo sapiens (Q9H488), Homo sapiens
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