GDP-fucose protein O-fucosyltransferase 1 also known as peptide-O-fucosyltransferase 1 (O-FucT-1) is an enzyme that in humans is encoded by the POFUT1gene.
POFUT-1 belongs to the O-Fuc family of proteins all which is involved in the transferring of o-fucose from GDP-β-L-fucose to substrates. POFUT-1 responsible for adding fucose sugars in O linkage to serine or threonine residues between the second and third conserved cysteines in EGF-like repeats on the Notch protein.[1] The protein is an inverting glycosyltransferase, which means that the enzyme uses GDP-β-L-fucose as a donor substrate and transfers the fucose in O linkage to the protein producing fucose-α-O-serine/threonine.
When the gene for POFUT1 is knocked out, or the expression is decreased to very low levels, all Notch signaling is destroyed, which means that fucose on Notch is essential for Notch function. Why this is the case is not yet well understood.
Pre-NOTCH proteins are translated and deposited in to the endoplasmic reticulum and are then first modified by POFUT-1 then by PGLUT-1 then exported the Golgi apparatus. in the endoplasmic reticulum POFUT-1 utilizes its sub-strait GDP-β-L-fucose as a donor for the five carbon sugar fucose. Fucose is then attached to a serine amino acid residue. Once Pre-notch is done being modified by POFUT-1 and POFUT-2, it is then exported to the Golgi apparatus where it is further modified and exported and incorporated into the cell membrane.
Species distributionedit
As NOTCH signaling is conserved in most multi-cellular life, so to are the processes that are involved in the pathway. Because of NOTCH presence in most life forms, not just limited to the kingdom Animalia, it is also present in the kingdom Plantae and kingdom Fungi. There are several different Homologs in POFUT-1 present in many kingdoms of life.
As a drug targetedit
Because POFUT-1 is a key protein in the production of NOTCH signaling protein it has been the target of much research to disrupt it for the purpose of cancer treatment and prevention.
Referencesedit
^Stahl M, Uemura K, Ge C, Shi S, Tashima Y, Stanley P (May 2008). "Roles of Pofut1 and O-fucose in mammalian Notch signaling". The Journal of Biological Chemistry. 283 (20): 13638–51. doi:10.1074/jbc.M802027200. PMC2376238. PMID 18347015.
^"POFUT1 Symbol Report | HUGO Gene Nomenclature Committee". www.genenames.org. Retrieved 2016-11-08.
External linksedit
O-fucosyltransferase+1,+Drosophila at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
fucose, protein, fucosyltransferase, also, known, peptide, fucosyltransferase, fuct, enzyme, that, humans, encoded, pofut1, gene, protein, fucosyltransferase, 1identifierssymbolpofut1ncbi, gene23509hgnc14988omim607491refseqnm, 172236uniprotq9h488other, dataec,. GDP fucose protein O fucosyltransferase 1 also known as peptide O fucosyltransferase 1 O FucT 1 is an enzyme that in humans is encoded by the POFUT1 gene protein O fucosyltransferase 1IdentifiersSymbolPOFUT1NCBI gene23509HGNC14988OMIM607491RefSeqNM 172236UniProtQ9H488Other dataEC number2 4 1 221LocusChr 20 q11Search forStructuresSwiss modelDomainsInterPro POFUT 1 belongs to the O Fuc family of proteins all which is involved in the transferring of o fucose from GDP b L fucose to substrates POFUT 1 responsible for adding fucose sugars in O linkage to serine or threonine residues between the second and third conserved cysteines in EGF like repeats on the Notch protein 1 The protein is an inverting glycosyltransferase which means that the enzyme uses GDP b L fucose as a donor substrate and transfers the fucose in O linkage to the protein producing fucose a O serine threonine When the gene for POFUT1 is knocked out or the expression is decreased to very low levels all Notch signaling is destroyed which means that fucose on Notch is essential for Notch function Why this is the case is not yet well understood Almost all glycosyltransferases reside in the Golgi apparatus However POFUT1 as well as the related enzyme POFUT2 have recently been shown to reside in the endoplasmic reticulum Contents 1 Nomenclature 2 Post translational modification 3 Species distribution 4 As a drug target 5 References 6 External linksNomenclature editGDP fucose protein O fucosyltransferase 1 is also known as Protein O fucosyltransferase 2 O FucT 1 FUT12 OFUCT1 O FUTPost translational modification edit nbsp POFUT 1 is an important protein in the post transitional modification of the notch signal protein POFUT 1 is involved in the attachment of fucose sugars to proteins However a key pathway is the Post transitional Modification of NOTCH signal proteins Pre NOTCH proteins are translated and deposited in to the endoplasmic reticulum and are then first modified by POFUT 1 then by PGLUT 1 then exported the Golgi apparatus in the endoplasmic reticulum POFUT 1 utilizes its sub strait GDP b L fucose as a donor for the five carbon sugar fucose Fucose is then attached to a serine amino acid residue Once Pre notch is done being modified by POFUT 1 and POFUT 2 it is then exported to the Golgi apparatus where it is further modified and exported and incorporated into the cell membrane Species distribution editAs NOTCH signaling is conserved in most multi cellular life so to are the processes that are involved in the pathway Because of NOTCH presence in most life forms not just limited to the kingdom Animalia it is also present in the kingdom Plantae and kingdom Fungi There are several different Homologs in POFUT 1 present in many kingdoms of life As a drug target editBecause POFUT 1 is a key protein in the production of NOTCH signaling protein it has been the target of much research to disrupt it for the purpose of cancer treatment and prevention References edit Stahl M Uemura K Ge C Shi S Tashima Y Stanley P May 2008 Roles of Pofut1 and O fucose in mammalian Notch signaling The Journal of Biological Chemistry 283 20 13638 51 doi 10 1074 jbc M802027200 PMC 2376238 PMID 18347015 POFUT1 Symbol Report HUGO Gene Nomenclature Committee www genenames org Retrieved 2016 11 08 External links editO fucosyltransferase 1 Drosophila at the U S National Library of Medicine Medical Subject Headings MeSH POFUT 1 GeneCards Weizmann Institute of Science POFUT1 Symbol Report HUGO Gene Nomenclature Committee Portal nbsp Biology Retrieved from https en wikipedia org w index php title GDP fucose protein O fucosyltransferase 1 amp oldid 1221742753, wikipedia, wiki, book, books, library,
