GDP-fucose protein O-fucosyltransferase 1 (POFUT1)
The protein contains 388 amino acids for an estimated molecular weight of 43956 Da.
Catalyzes the reaction that attaches fucose through an O-glycosidic linkage to a conserved serine or threonine residue found in the consensus sequence C2-X(4,5)-[S/T]-C3 of EGF domains, where C2 and C3 are the second and third conserved cysteines. Specifically uses GDP-fucose as donor substrate and proper disulfide pairing of the substrate EGF domains is required for fucose transfer. Plays a crucial role in NOTCH signaling. Initial fucosylation of NOTCH by POFUT1 generates a substrate for FRINGE/RFNG, an acetylglucosaminyltransferase that can then extend the fucosylation on the NOTCH EGF repeats. This extended fucosylation is required for optimal ligand binding and canonical NOTCH signaling induced by DLL1 or JAGGED1. Fucosylates AGRN and determines its ability to cluster acetylcholine receptors (AChRs). (updated: Oct. 10, 2018)
Protein identification was indicated in the following studies:
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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| Variant | Description |
|---|---|
| dbSNP:rs17268666 | |
| dbSNP:rs35259534 |
No binding partner found
Biological Process
Angiogenesis
Fucose metabolic process
Heart development
Nervous system development
Notch signaling pathway
O-glycan processing
Protein O-linked fucosylation
Protein O-linked glycosylation
Regulation of Notch signaling pathway
Regulation of transcription, DNA-templated
Somitogenesis
The reference OMIM entry for this protein is 607491
Protein o-fucosyltransferase 1; pofut1
Ofut1; ofuct1
Kiaa0180
DESCRIPTION
The O-fucose modification is found on epidermal growth factor (EGF; 131530)-like repeats of a number of cell surface and secreted proteins. O-fucose glycans play important roles in ligand-induced receptor signaling. For example, elongation of O-fucose on Notch (190198) by the beta-1,3-N-acetylglucosaminyltransferase fringe (602577) modulates the ability of Notch to respond to its ligands. The enzyme that adds O-fucose to EGF-like repeats is GDP-fucose protein O-fucosyltransferase, or POFUT1 (Wang et al., 2001).CLONING
By screening sequence databases using a probe deduced from N-terminal sequence analysis of Pofut1 purified from CHO cells, Wang et al. (2001) identified a partial cDNA, KIAA0180, that had been cloned by Nagase et al. (1996). Wang et al. (2001) obtained a full-length cDNA encoding POFUT1, which they called OFUCT1, by screening a human heart cDNA library. The full-length cDNA encodes a 388-amino acid protein with a predicted N-terminal transmembrane sequence typical of a type II membrane orientation. Wang et al. (2001) identified POFUT1 homologs in mouse, Drosophila, and C. elegans that share 90.4%, 41.2%, and 29.4% amino acid identity with human POFUT1, respectively. Northern blot analysis detected major POFUT1 transcripts of approximately 5 kb in all tissues examined, consistent with the widespread localization of the O-fucose modification. Several other weaker bands were also detected, suggesting that other transcripts may be expressed in some tissues. Li et al. (2013) demonstrated that Pofut1 is expressed in the skin and other organs of zebrafish, with highest expression in the testis, fin, and ovary.MAPPING
By genomic sequence analysis, Wang et al. (2001) mapped the POFUT1 gene to chromosome 20q11, near the centromere. It is located between the PLAGL2 (604866) and KIF3B (603754) genes. They mapped the mouse gene to a homologous region of mouse chromosome 2.GENE FUNCTION
Wang et al. (2001) showed that expression of a soluble form of human POFUT1 in insect cells yielded a protein of the predicted molecular mass with kinetic and enzymatic properties similar to those of Pofut1 purified from CHO cells. Using RNA interference to decrease Pofut1 expression in Drosophila, Okajima and Irvine (2002) demonstrated that O-linked fucose is positively required for Notch signaling, including both fringe-dependent and fringe-independent processes. The requirement for Pofut1 was found to be cell autonomous, in the signal-receiving cell, and upstream of Notch activation. The transcription of Pofut1 was developmentally regulated, and overexpression of Pofut1 inhibited Notch signaling. The authors concluded that POFUT1 is a core component of the Notch pathway that is required for the activation of Notch by its ligands and whose regulation may contribute to the pattern of Notch activation during development. Notch receptor signaling regulates cell growth and differentiation, and core components of Notch signaling pathways are conserved from Drosophila to humans. Shi and Stanley (2003) showed that mouse embryos lacking protein O-fucosyltransferase-1 die at midgestation with severe defects in somitogenesis, vasculogenesis, cardiogenesis, and neurogenesis. The phenotype is similar to that of embryos lacking downstream effectors of all Notch signaling pathways such as presenilins, and is different from null phenotypes of Cripto (187395), Notch receptor, Notch ligand, or Fringe. Protein O ... More on the omim web site
Feb. 23, 2019: Protein entry updated
Automatic update: comparative model was added.
Feb. 23, 2019: Protein entry updated
Automatic update: model status changed
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).
Oct. 19, 2018: Protein entry updated
Automatic update: OMIM entry 607491 was added.