Q91ZW2 (OFUT1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
GDP-fucose protein O-fucosyltransferase 1
EC=2.4.1.221

Alternative name(s):
Peptide-O-fucosyltransferase 1
Short name=O-FucT-1

Gene names

Name:

Pofut1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	393 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	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). Ref.4 Ref.5
Catalytic activity	Transfers an alpha-L-fucosyl residue from GDP-beta-L-fucose to the serine hydroxy group of a protein acceptor.
Pathway	Protein modification; protein glycosylation.
Subcellular location	Endoplasmic reticulum By similarity.
Developmental stage	Increased expression throughout embryo development. Ubiquitous expression at E9.5 and E11.5 with lower expression at E9.5. Ref.4
Post-translational modification	N-glycosylated By similarity.
Disruption phenotype	Early embryos of null mice are defective in somitogenesis. At E8.5, embryos are of normal size and appearance but somites adjacent to the presomitic mesoderm (PSM) are fused. In E8.25 embryos, expression of NOTCH target genes such as HES5 and JAG1 as well as LFNG and UNCX4.1 is severly reduced in somites. There is up-regulation of a number of these genes such as HES5 and LFNG as well as DLL1 and NOTCH1 in the neural tube and brain. Mice die at midgestation with severe defects in somitogenesis, vasculogenesis, cardiogenesis and neurogenesis. Ref.4
Miscellaneous	The cax (compact axial skeleton) spontaneous mutation is a hypomorphic allele that reduces Pofut1 expression and protein levels leading to reduced Notch signaling. cax mutant embryos have somites of variable size, partly abnormal Lfng expression, defective anterior-posterior somite patterning and abnormal axial skeleton development. Mice have kinky and shortened tails and shortened body length (Ref.6).
Sequence similarities	Belongs to the glycosyltransferase 68 family.

Ontologies

Keywords
Biological process	Carbohydrate metabolism Fucose metabolism Notch signaling pathway
Cellular component	Endoplasmic reticulum
Domain	Signal
Ligand	Manganese
Molecular function	Glycosyltransferase Transferase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Notch signaling pathway Inferred from mutant phenotype Ref.6. Source: UniProtKB angiogenesis Inferred from mutant phenotype Ref.4. Source: MGI fucose metabolic process Traceable author statement Ref.1. Source: MGI heart development Inferred from mutant phenotype Ref.4. Source: MGI nervous system development Inferred from mutant phenotype Ref.4. Source: MGI protein O-linked glycosylation Inferred from sequence or structural similarity. Source: UniProtKB somitogenesis Inferred from mutant phenotype Ref.4. Source: MGI
Cellular_component	endoplasmic reticulum Inferred from electronic annotation. Source: UniProtKB-SubCell membrane Inferred from sequence or structural similarity. Source: UniProtKB
Molecular_function	fucosyltransferase activity Inferred from sequence or structural similarity Ref.1. Source: UniProtKB peptide-O-fucosyltransferase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 30	30	Potential
	Chain	31 – 393	363	GDP-fucose protein O-fucosyltransferase 1		PRO_0000012149
Regions
	Region	49 – 51	3	Substrate binding By similarity
	Region	243 – 245	3	Substrate binding By similarity
	Region	361 – 362	2	Substrate binding By similarity
	Motif	390 – 393	4	Prevents secretion from ER Potential
Sites
	Binding site	340	1	Substrate By similarity
Amino acid modifications
	Glycosylation	67	1	N-linked (GlcNAc...) Potential
	Glycosylation	165	1	N-linked (GlcNAc...) Potential
	Disulfide bond	43 ↔ 45		By similarity
	Disulfide bond	131 ↔ 145		By similarity
	Disulfide bond	254 ↔ 288		By similarity
	Disulfide bond	272 ↔ 359		By similarity
Experimental info
	Sequence conflict	233	1	A → S in BAC32009. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q91ZW2 [UniParc]. Last modified December 1, 2001. Version 1. Checksum: D982104E95E5CF3B	FASTA	393	44,688
	10 20 30 40 50 60 MGAAAWAPPH LLLRASFLLL LLLLPLRGRS AGSWDLAGYL LYCPCMGRFG NQADHFLGSL 70 80 90 100 110 120 AFAKLLNRTL AVPPWIEYQH HKPPFTNLHV SYQKYFKLEP LQAYHRVVSL EDFMENLAPS 130 140 150 160 170 180 HWPPEKRVAY CFEVAAQRSP DKKTCPMKEG NPFGPFWDQF HVSFNKSELF TGISFSASYK 190 200 210 220 230 240 EQWTQRFPAK EHPVLALPGA PAQFPVLEEH RELQKYMVWS DEMVRTGEAL ISAHLVRPYV 250 260 270 280 290 300 GIHLRIGSDW KNACAMLKDG TAGSHFMASP QCVGYSRSTA TPLTMTMCLP DLKEIQRAVT 310 320 330 340 350 360 LWVRALNARS VYIATDSESY VSEIQQLFKD KVRVVSLKPE VAQIDLYILG QADHFIGNCV 370 380 390 SSFTAFVKRE RDLHGRQSSF FGMDRPSQLR DEF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Modification of epidermal growth factor-like repeats with O-fucose: molecular cloning and expression of a novel GDP-fucose protein O-fucosyltransferase." Wang Y., Shao L., Shi S., Harris R.J., Spellman M.W., Stanley P., Haltiwanger R.S. J. Biol. Chem. 276:40338-40345(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: 129/SvJ. Tissue: Liver.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Head.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: FVB/N-3. Tissue: Mammary gland.
[4]	"Protein O-fucosyltransferase 1 is an essential component of Notch signaling pathways." Shi S., Stanley P. Proc. Natl. Acad. Sci. U.S.A. 100:5234-5239(2003) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE, FUNCTION.
[5]	"O-fucosylation of muscle agrin determines its ability to cluster acetylcholine receptors." Kim M.L., Chandrasekharan K., Glass M., Shi S., Stahl M.C., Kaspar B., Stanley P., Martin P.T. Mol. Cell. Neurosci. 39:452-464(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[6]	"Notch signalling in the paraxial mesoderm is most sensitive to reduced Pofut1 levels during early mouse development." Schuster-Gossler K., Harris B., Johnson K.R., Serth J., Gossler A. BMC Dev. Biol. 9:6-6(2009) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION OF THE CAX MUTATION.
+	Additional computationally mapped references.

Web resources

Functional Glycomics Gateway - GTase

Peptide-O-fucosyltransferase 1

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF375885 mRNA. Translation: AAL09577.1. AK044629 mRNA. Translation: BAC32009.1. AK132301 mRNA. Translation: BAE21090.1. BC046295 mRNA. Translation: AAH46295.1.
IPI	IPI00131488.
RefSeq	NP_536711.3. NM_080463.3.
UniGene	Mm.293761.
3D structure databases
ProteinModelPortal	Q91ZW2.
SMR	Q91ZW2. Positions 35-383.
ModBase	Search...
Protein family/group databases
CAZy	GT65. Glycosyltransferase Family 65.
PTM databases
PhosphoSite	Q91ZW2.
Proteomic databases
PaxDb	Q91ZW2.
PRIDE	Q91ZW2.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000049863; ENSMUSP00000053122; ENSMUSG00000046020.
GeneID	140484.
KEGG	mmu:140484.
Organism-specific databases
CTD	23509.
MGI	MGI:2153207. Pofut1.
Phylogenomic databases
eggNOG	NOG250895.
GeneTree	ENSGT00390000015634.
HOGENOM	HOG000231651.
HOVERGEN	HBG059976.
InParanoid	Q91ZW2.
KO	K03691.
OMA	RNGIDWV.
OrthoDB	EOG43TZVN.
Enzyme and pathway databases
UniPathway	UPA00378.
Gene expression databases
ArrayExpress	Q91ZW2.
Bgee	Q91ZW2.
CleanEx	MM_POFUT1.
Genevestigator	Q91ZW2.
GermOnline	ENSMUSG00000046020. Mus musculus.
Family and domain databases
InterPro	IPR019378. GDP-Fuc_O-FucTrfase. [Graphical view]
Pfam	PF10250. O-FucT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	369790.
SOURCE	Search...

Entry information

Entry name

OFUT1_MOUSE

Accession

Primary (citable) accession number: Q91ZW2
Secondary accession number(s): Q3V1R0, Q8C8R4

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2002
Last sequence update:	December 1, 2001
Last modified:	May 1, 2013
This is version 101 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program