Q9H488 (OFUT1_HUMAN) 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
Synonyms:	FUT12, KIAA0180

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	388 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.1 Ref.8
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.
Tissue specificity	Highly expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas. Ref.1
Post-translational modification	N-glycosylated.
Sequence similarities	Belongs to the glycosyltransferase 68 family.
Biophysicochemical properties	Kinetic parameters: KM=6 µM for F7 EGF domain Ref.1 KM=4 µM for GDP-fucose Vmax=3 µmol/min/mg enzyme

Ontologies

Keywords
Biological process	Carbohydrate metabolism Fucose metabolism Notch signaling pathway
Cellular component	Endoplasmic reticulum
Coding sequence diversity	Alternative splicing Polymorphism
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 Non-traceable author statement PubMed 15653671. Source: UniProtKB O-glycan processing Traceable author statement PubMed 11698403. Source: UniProtKB angiogenesis Inferred from electronic annotation. Source: Compara embryo development Non-traceable author statement PubMed 11698403. Source: UniProtKB fucose metabolic process Inferred from electronic annotation. Source: UniProtKB-KW heart development Inferred from electronic annotation. Source: Compara nervous system development Inferred from electronic annotation. Source: Compara regulation of transcription, DNA-dependent Non-traceable author statement PubMed 11698403. Source: UniProtKB somitogenesis Inferred from electronic annotation. Source: Compara
Cellular_component	endoplasmic reticulum Inferred from direct assay PubMed 15653671. Source: UniProtKB membrane Inferred from direct assay Ref.1PubMed 9023546. Source: UniProtKB
Molecular_function	peptide-O-fucosyltransferase activity Inferred from direct assay PubMed 15653671. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9H488-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9H488-2)

The sequence of this isoform differs from the canonical sequence as follows:
     182-388: FSPKEHPVLA...DRPPKLRDEF → RENHSCVTLLFPR

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 26	26	Potential
	Chain	27 – 388	362	GDP-fucose protein O-fucosyltransferase 1		PRO_0000012148
Regions
	Region	44 – 46	3	Substrate binding By similarity
	Region	238 – 240	3	Substrate binding By similarity
	Region	356 – 357	2	Substrate binding By similarity
	Motif	385 – 388	4	Prevents secretion from ER Potential
Sites
	Binding site	335	1	Substrate By similarity
Amino acid modifications
	Glycosylation	62	1	N-linked (GlcNAc...) Potential
	Glycosylation	160	1	N-linked (GlcNAc...) Ref.9
	Disulfide bond	38 ↔ 40		By similarity
	Disulfide bond	126 ↔ 140		By similarity
	Disulfide bond	249 ↔ 283		By similarity
	Disulfide bond	267 ↔ 354		By similarity
Natural variations
	Alternative sequence	182 – 388	207	FSPKE…LRDEF → RENHSCVTLLFPR in isoform 2.		VSP_001809
	Natural variant	322	1	L → F. Corresponds to variant rs17268666 [ dbSNP | Ensembl ].		VAR_049231
	Natural variant	348	1	D → N. Corresponds to variant rs35259534 [ dbSNP | Ensembl ].		VAR_049232

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 3FACCCA434D02415	FASTA	388	43,956
	10 20 30 40 50 60 MGAAAWARPL SVSFLLLLLP LPGMPAGSWD PAGYLLYCPC MGRFGNQADH FLGSLAFAKL 70 80 90 100 110 120 LNRTLAVPPW IEYQHHKPPF TNLHVSYQKY FKLEPLQAYH RVISLEDFME KLAPTHWPPE 130 140 150 160 170 180 KRVAYCFEVA AQRSPDKKTC PMKEGNPFGP FWDQFHVSFN KSELFTGISF SASYREQWSQ 190 200 210 220 230 240 RFSPKEHPVL ALPGAPAQFP VLEEHRPLQK YMVWSDEMVK TGEAQIHAHL VRPYVGIHLR 250 260 270 280 290 300 IGSDWKNACA MLKDGTAGSH FMASPQCVGY SRSTAAPLTM TMCLPDLKEI QRAVKLWVRS 310 320 330 340 350 360 LDAQSVYVAT DSESYVPELQ QLFKGKVKVV SLKPEVAQVD LYILGQADHF IGNCVSSFTA 370 380 FVKRERDLQG RPSSFFGMDR PPKLRDEF
	Isoform 2 [UniParc]. Checksum: 5ADE77CE45147644	FASTA	194	22,338
	10 20 30 40 50 60 MGAAAWARPL SVSFLLLLLP LPGMPAGSWD PAGYLLYCPC MGRFGNQADH FLGSLAFAKL 70 80 90 100 110 120 LNRTLAVPPW IEYQHHKPPF TNLHVSYQKY FKLEPLQAYH RVISLEDFME KLAPTHWPPE 130 140 150 160 170 180 KRVAYCFEVA AQRSPDKKTC PMKEGNPFGP FWDQFHVSFN KSELFTGISF SASYREQWSQ 190 RRENHSCVTL LFPR

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] (ISOFORM 1), FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, TISSUE SPECIFICITY. Tissue: Heart.
[2]	"Prediction of the coding sequences of unidentified human genes. V. The coding sequences of 40 new genes (KIAA0161-KIAA0200) deduced by analysis of cDNA clones from human cell line KG-1." Nagase T., Seki N., Ishikawa K., Tanaka A., Nomura N. DNA Res. 3:17-24(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Bone marrow.
[3]	"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones." Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T. DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract] Cited for: SEQUENCE REVISION.
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[5]	"The DNA sequence and comparative analysis of human chromosome 20." Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J. Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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] (ISOFORM 2). Tissue: Brain.
[8]	"O-linked fucose and other post-translational modifications unique to EGF modules." Harris R.J., Spellman M.W. Glycobiology 3:219-224(1993) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry." Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H. J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract] Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-160, MASS SPECTROMETRY. Tissue: Liver.
[10]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Web resources

GGDB

GlycoGene database

Functional Glycomics Gateway - GTase

Peptide-O-fucosyltransferase 1

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF375884 mRNA. Translation: AAL09576.1. D80002 mRNA. Translation: BAA11497.2. AL121897 Genomic DNA. Translation: CAC16424.1. AL121897 Genomic DNA. Translation: CAH73300.1. AK291033 mRNA. Translation: BAF83722.1. CH471077 Genomic DNA. Translation: EAW76383.1. CH471077 Genomic DNA. Translation: EAW76384.1. CH471077 Genomic DNA. Translation: EAW76385.1. BC000582 mRNA. Translation: AAH00582.1.
IPI	IPI00058192. IPI00218176.
RefSeq	NP_056167.1. NM_015352.1. NP_758436.1. NM_172236.1.
UniGene	Hs.472409.
3D structure databases
ProteinModelPortal	Q9H488.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9H488. 2 interactions.
STRING	9606.ENSP00000364902.
Protein family/group databases
CAZy	GT65. Glycosyltransferase Family 65.
PTM databases
PhosphoSite	Q9H488.
Polymorphism databases
DMDM	23396787.
Proteomic databases
PaxDb	Q9H488.
PeptideAtlas	Q9H488.
PRIDE	Q9H488.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000375730; ENSP00000364882; ENSG00000101346. ENST00000375749; ENSP00000364902; ENSG00000101346.
GeneID	23509.
KEGG	hsa:23509.
UCSC	uc002wxo.3. human. uc002wxp.3. human.
Organism-specific databases
CTD	23509.
GeneCards	GC20P030795.
HGNC	HGNC:14988. POFUT1.
HPA	HPA054519.
MIM	607491. gene.
neXtProt	NX_Q9H488.
PharmGKB	PA33495.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG250895.
HOGENOM	HOG000231651.
HOVERGEN	HBG059976.
InParanoid	Q9H488.
KO	K03691.
OMA	RNGIDWV.
OrthoDB	EOG43TZVN.
PhylomeDB	Q9H488.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
UniPathway	UPA00378.
Gene expression databases
ArrayExpress	Q9H488.
Bgee	Q9H488.
CleanEx	HS_POFUT1.
Genevestigator	Q9H488.
GermOnline	ENSG00000101346. Homo sapiens.
Family and domain databases
InterPro	IPR019378. GDP-Fuc_O-FucTrfase. [Graphical view]
Pfam	PF10250. O-FucT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	POFUT1. human.
GenomeRNAi	23509.
NextBio	45915.
SOURCE	Search...

Entry information

Entry name

OFUT1_HUMAN

Accession

Primary (citable) accession number: Q9H488
Secondary accession number(s): A8K4R8 , E1P5M4, Q14685, Q5W185, Q9BW76

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 19, 2002
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 110 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.