OFUT1_MOUSE
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 03-AUG-2022, entry version 159.
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; Note=Peptide-
CC O-fucosyltransferase 1;
CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_mou_619";
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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 GlyGen; Q91ZW2; 2 sites, 2 N-linked glycans (1 site).
DR PhosphoSitePlus; Q91ZW2; -.
DR EPD; Q91ZW2; -.
DR MaxQB; Q91ZW2; -.
DR PaxDb; Q91ZW2; -.
DR PeptideAtlas; Q91ZW2; -.
DR PRIDE; Q91ZW2; -.
DR ProteomicsDB; 294165; -.
DR Antibodypedia; 25350; 229 antibodies from 31 providers.
DR Ensembl; ENSMUST00000049863; ENSMUSP00000053122; ENSMUSG00000046020.
DR GeneID; 140484; -.
DR KEGG; mmu:140484; -.
DR UCSC; uc008nhm.1; mouse.
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; 1127619at2759; -.
DR PhylomeDB; Q91ZW2; -.
DR TreeFam; TF314805; -.
DR BRENDA; 2.4.1.221; 3474.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 140484; 0 hits in 68 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 214 other tissues.
DR ExpressionAtlas; Q91ZW2; baseline and differential.
DR Genevisible; Q91ZW2; MM.
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 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 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
