ID OFUT1_MOUSE Reviewed; 393 AA. AC Q91ZW2; Q3V1R0; Q8C8R4; DT 19-SEP-2002, integrated into UniProtKB/Swiss-Prot. DT 01-DEC-2001, sequence version 1. DT 24-JAN-2024, entry version 166. DE RecName: Full=GDP-fucose protein O-fucosyltransferase 1; DE EC=2.4.1.221 {ECO:0000305|PubMed:18775496}; DE AltName: Full=Peptide-O-fucosyltransferase 1; DE Short=O-FucT-1; DE Flags: Precursor; GN Name=Pofut1; OS Mus musculus (Mouse). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; OC Murinae; Mus; Mus. OX NCBI_TaxID=10090; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC STRAIN=129/SvJ; TISSUE=Liver; 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 [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=C57BL/6J; TISSUE=Head; RX PubMed=16141072; DOI=10.1126/science.1112014; RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J., RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.; RT "The transcriptional landscape of the mammalian genome."; RL Science 309:1559-1563(2005). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC STRAIN=FVB/N-3; TISSUE=Mammary gland; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE, AND FUNCTION. RX PubMed=12697902; DOI=10.1073/pnas.0831126100; RA Shi S., Stanley P.; RT "Protein O-fucosyltransferase 1 is an essential component of Notch RT signaling pathways."; RL Proc. Natl. Acad. Sci. U.S.A. 100:5234-5239(2003). RN [5] RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY. RX PubMed=18775496; DOI=10.1016/j.mcn.2008.07.026; RA Kim M.L., Chandrasekharan K., Glass M., Shi S., Stahl M.C., Kaspar B., RA Stanley P., Martin P.T.; RT "O-fucosylation of muscle agrin determines its ability to cluster RT acetylcholine receptors."; RL Mol. Cell. Neurosci. 39:452-464(2008). RN [6] RP CHARACTERIZATION OF THE CAX MUTATION. RX PubMed=19161597; DOI=10.1186/1471-213x-9-6; RA Schuster-Gossler K., Harris B., Johnson K.R., Serth J., Gossler A.; RT "Notch signalling in the paraxial mesoderm is most sensitive to reduced RT Pofut1 levels during early mouse development."; RL BMC Dev. Biol. 9:6-6(2009). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Heart, Kidney, Liver, Lung, Pancreas, Spleen, and Testis; RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001; RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R., RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.; RT "A tissue-specific atlas of mouse protein phosphorylation and expression."; RL Cell 143:1174-1189(2010). 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 DLL1 or JAGGED1. Fucosylates AGRN and determines CC its ability to cluster acetylcholine receptors (AChRs). CC {ECO:0000269|PubMed:12697902, ECO:0000269|PubMed:18775496}. 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:0000305|PubMed:18775496}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:63645; CC Evidence={ECO:0000305|PubMed:18775496}; 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:0000250|UniProtKB:Q9H488}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70492; CC Evidence={ECO:0000250|UniProtKB:Q9H488}; CC -!- PATHWAY: Protein modification; protein glycosylation. CC {ECO:0000305|PubMed:18775496}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum CC {ECO:0000250|UniProtKB:Q6EV70}. CC -!- DEVELOPMENTAL STAGE: Increased expression throughout embryo CC development. Ubiquitous expression at 9.5 dpc and 11.5 dpc with lower CC expression at 9.5 dpc. {ECO:0000269|PubMed:12697902}. CC -!- PTM: N-glycosylated. {ECO:0000250|UniProtKB:P83337}. CC -!- DISRUPTION PHENOTYPE: Early embryos of null mice are defective in CC somitogenesis. At 8.5 dpc, embryos are of normal size and appearance CC but somites adjacent to the presomitic mesoderm (PSM) are fused. In CC 8.25 dpc embryos, expression of NOTCH target genes such as HES5 and CC JAG1 as well as LFNG and UNCX4.1 is severely reduced in somites. There CC is up-regulation of a number of these genes such as HES5 and LFNG as CC well as DLL1 and NOTCH1 in the neural tube and brain. Mice die at CC midgestation with severe defects in somitogenesis, vasculogenesis, CC cardiogenesis and neurogenesis. {ECO:0000269|PubMed:12697902}. CC -!- MISCELLANEOUS: The cax (compact axial skeleton) spontaneous mutation is CC a hypomorphic allele that reduces Pofut1 expression and protein levels CC leading to reduced Notch signaling. cax mutant embryos have somites of CC variable size, partly abnormal Lfng expression, defective anterior- CC posterior somite patterning and abnormal axial skeleton development. CC Mice have kinky and shortened tails and shortened body length CC (PubMed:19161597). {ECO:0000305|PubMed:19161597}. CC -!- SIMILARITY: Belongs to the glycosyltransferase 65 family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - GTase; CC Note=Peptide-O-fucosyltransferase 1; CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_mou_619"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF375885; AAL09577.1; -; mRNA. DR EMBL; AK044629; BAC32009.1; -; mRNA. DR EMBL; AK132301; BAE21090.1; -; mRNA. DR EMBL; BC046295; AAH46295.1; -; mRNA. DR CCDS; CCDS16909.1; -. DR RefSeq; NP_536711.3; NM_080463.3. DR PDB; 5KXH; X-ray; 1.33 A; A=33-384. DR PDB; 5KXQ; X-ray; 1.90 A; A/B/C/D=32-385. DR PDB; 5KY0; X-ray; 1.53 A; A=33-384. DR PDB; 5KY2; X-ray; 1.47 A; A=33-384. DR PDB; 5KY3; X-ray; 1.53 A; A=33-384. DR PDB; 5KY4; X-ray; 1.47 A; A=33-384. DR PDB; 5KY5; X-ray; 1.50 A; A=33-384. DR PDB; 5KY7; X-ray; 1.60 A; A=33-384. DR PDB; 5KY8; X-ray; 1.65 A; A=33-384. DR PDB; 5KY9; X-ray; 1.83 A; A=33-384. DR PDBsum; 5KXH; -. DR PDBsum; 5KXQ; -. DR PDBsum; 5KY0; -. DR PDBsum; 5KY2; -. DR PDBsum; 5KY3; -. DR PDBsum; 5KY4; -. DR PDBsum; 5KY5; -. DR PDBsum; 5KY7; -. DR PDBsum; 5KY8; -. DR PDBsum; 5KY9; -. DR AlphaFoldDB; Q91ZW2; -. DR SMR; Q91ZW2; -. DR BioGRID; 228259; 3. DR STRING; 10090.ENSMUSP00000053122; -. DR CAZy; GT65; Glycosyltransferase Family 65. DR GlyConnect; 2335; 2 N-Linked glycans (1 site). DR GlyCosmos; Q91ZW2; 2 sites, 2 glycans. DR GlyGen; Q91ZW2; 2 sites, 2 N-linked glycans (1 site). DR iPTMnet; Q91ZW2; -. DR PhosphoSitePlus; Q91ZW2; -. DR SwissPalm; Q91ZW2; -. DR EPD; Q91ZW2; -. DR MaxQB; Q91ZW2; -. DR PaxDb; 10090-ENSMUSP00000053122; -. DR PeptideAtlas; Q91ZW2; -. DR ProteomicsDB; 294165; -. DR Pumba; Q91ZW2; -. DR Antibodypedia; 25350; 254 antibodies from 31 providers. DR Ensembl; ENSMUST00000049863.12; ENSMUSP00000053122.6; ENSMUSG00000046020.14. DR GeneID; 140484; -. DR KEGG; mmu:140484; -. DR UCSC; uc008nhm.1; mouse. DR AGR; MGI:2153207; -. DR CTD; 23509; -. DR MGI; MGI:2153207; Pofut1. DR VEuPathDB; HostDB:ENSMUSG00000046020; -. DR eggNOG; KOG3849; Eukaryota. DR GeneTree; ENSGT00390000015634; -. DR InParanoid; Q91ZW2; -. DR OMA; QRFPPKE; -. DR OrthoDB; 5384121at2759; -. DR PhylomeDB; Q91ZW2; -. DR TreeFam; TF314805; -. DR BRENDA; 2.4.1.221; 3474. DR UniPathway; UPA00378; -. DR BioGRID-ORCS; 140484; 0 hits in 73 CRISPR screens. DR ChiTaRS; Pofut1; mouse. DR PRO; PR:Q91ZW2; -. DR Proteomes; UP000000589; Chromosome 2. DR RNAct; Q91ZW2; Protein. DR Bgee; ENSMUSG00000046020; Expressed in epithelium of small intestine and 216 other cell types or tissues. DR ExpressionAtlas; Q91ZW2; baseline and differential. DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI. 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:MGI. DR GO; GO:0001525; P:angiogenesis; IMP:MGI. DR GO; GO:0006004; P:fucose metabolic process; TAS:MGI. DR GO; GO:0007507; P:heart development; IMP:MGI. DR GO; GO:0007399; P:nervous system development; IMP:MGI. DR GO; GO:0007219; P:Notch signaling pathway; IMP:UniProtKB. DR GO; GO:0036066; P:protein O-linked fucosylation; ISO:MGI. 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; IMP:MGI. DR CDD; cd11302; O-FucT-1; 1. DR DisProt; DP02659; -. 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; Q91ZW2; MM. PE 1: Evidence at protein level; KW 3D-structure; Carbohydrate metabolism; Disulfide bond; KW Endoplasmic reticulum; Fucose metabolism; Glycoprotein; KW Glycosyltransferase; Manganese; Notch signaling pathway; KW Reference proteome; Signal; Transferase. FT SIGNAL 1..30 FT /evidence="ECO:0000255" FT CHAIN 31..393 FT /note="GDP-fucose protein O-fucosyltransferase 1" FT /id="PRO_0000012149" FT MOTIF 390..393 FT /note="Prevents secretion from ER" FT /evidence="ECO:0000255" FT BINDING 48..51 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9H488" FT BINDING 243..245 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9H488" FT BINDING 345 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9H488" FT BINDING 362..363 FT /ligand="substrate" FT /evidence="ECO:0000250|UniProtKB:Q9H488" FT CARBOHYD 67 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 165 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 43..45 FT /evidence="ECO:0000250|UniProtKB:Q9H488" FT DISULFID 131..145 FT /evidence="ECO:0000250|UniProtKB:Q9H488" FT DISULFID 254..288 FT /evidence="ECO:0000250|UniProtKB:Q9H488" FT DISULFID 272..359 FT /evidence="ECO:0000250|UniProtKB:Q9H488" FT CONFLICT 233 FT /note="A -> S (in Ref. 2; BAC32009)" FT /evidence="ECO:0000305" FT STRAND 39..42 FT /evidence="ECO:0007829|PDB:5KXH" FT STRAND 46..48 FT /evidence="ECO:0007829|PDB:5KXH" FT HELIX 49..66 FT /evidence="ECO:0007829|PDB:5KXH" FT STRAND 69..72 FT /evidence="ECO:0007829|PDB:5KXH" FT STRAND 75..77 FT /evidence="ECO:0007829|PDB:5KXH" FT STRAND 88..90 FT /evidence="ECO:0007829|PDB:5KXH" FT HELIX 92..95 FT /evidence="ECO:0007829|PDB:5KXH" FT HELIX 99..103 FT /evidence="ECO:0007829|PDB:5KXH" FT STRAND 107..109 FT /evidence="ECO:0007829|PDB:5KXH" FT HELIX 110..116 FT /evidence="ECO:0007829|PDB:5KXH" FT HELIX 118..121 FT /evidence="ECO:0007829|PDB:5KXH" FT HELIX 124..126 FT /evidence="ECO:0007829|PDB:5KXH" FT STRAND 128..132 FT /evidence="ECO:0007829|PDB:5KXH" FT HELIX 133..137 FT /evidence="ECO:0007829|PDB:5KXH" FT STRAND 142..144 FT /evidence="ECO:0007829|PDB:5KXH" FT STRAND 147..150 FT /evidence="ECO:0007829|PDB:5KY4" FT HELIX 153..158 FT /evidence="ECO:0007829|PDB:5KXH" FT TURN 159..161 FT /evidence="ECO:0007829|PDB:5KXH" FT STRAND 165..170 FT /evidence="ECO:0007829|PDB:5KXH" FT HELIX 177..179 FT /evidence="ECO:0007829|PDB:5KXH" FT HELIX 180..186 FT /evidence="ECO:0007829|PDB:5KXH" FT TURN 189..191 FT /evidence="ECO:0007829|PDB:5KXH" FT STRAND 193..199 FT /evidence="ECO:0007829|PDB:5KXH" FT HELIX 208..216 FT /evidence="ECO:0007829|PDB:5KXH" FT HELIX 221..234 FT /evidence="ECO:0007829|PDB:5KXH" FT STRAND 237..244 FT /evidence="ECO:0007829|PDB:5KXH" FT HELIX 248..250 FT /evidence="ECO:0007829|PDB:5KXH" FT HELIX 251..255 FT /evidence="ECO:0007829|PDB:5KXH" FT STRAND 260..262 FT /evidence="ECO:0007829|PDB:5KY9" FT TURN 267..269 FT /evidence="ECO:0007829|PDB:5KXH" FT HELIX 270..273 FT /evidence="ECO:0007829|PDB:5KXH" FT STRAND 275..278 FT /evidence="ECO:0007829|PDB:5KY8" FT HELIX 285..288 FT /evidence="ECO:0007829|PDB:5KXH" FT HELIX 292..306 FT /evidence="ECO:0007829|PDB:5KXH" FT STRAND 309..317 FT /evidence="ECO:0007829|PDB:5KXH" FT HELIX 321..325 FT /evidence="ECO:0007829|PDB:5KXH" FT TURN 326..330 FT /evidence="ECO:0007829|PDB:5KY2" FT STRAND 332..336 FT /evidence="ECO:0007829|PDB:5KXH" FT HELIX 342..350 FT /evidence="ECO:0007829|PDB:5KXH" FT STRAND 353..357 FT /evidence="ECO:0007829|PDB:5KXH" FT HELIX 362..373 FT /evidence="ECO:0007829|PDB:5KXH" FT STRAND 378..380 FT /evidence="ECO:0007829|PDB:5KXH" SQ SEQUENCE 393 AA; 44688 MW; D982104E95E5CF3B CRC64; MGAAAWAPPH LLLRASFLLL LLLLPLRGRS AGSWDLAGYL LYCPCMGRFG NQADHFLGSL AFAKLLNRTL AVPPWIEYQH HKPPFTNLHV SYQKYFKLEP LQAYHRVVSL EDFMENLAPS HWPPEKRVAY CFEVAAQRSP DKKTCPMKEG NPFGPFWDQF HVSFNKSELF TGISFSASYK EQWTQRFPAK EHPVLALPGA PAQFPVLEEH RELQKYMVWS DEMVRTGEAL ISAHLVRPYV GIHLRIGSDW KNACAMLKDG TAGSHFMASP QCVGYSRSTA TPLTMTMCLP DLKEIQRAVT LWVRALNARS VYIATDSESY VSEIQQLFKD KVRVVSLKPE VAQIDLYILG QADHFIGNCV SSFTAFVKRE RDLHGRQSSF FGMDRPSQLR DEF //