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Protein

GDP-fucose protein O-fucosyltransferase 1

Gene

POFUT1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).3 Publications

Catalytic activityi

Transfers an alpha-L-fucosyl residue from GDP-beta-L-fucose to the serine hydroxy group of a protein acceptor.1 Publication

Kineticsi

  1. KM=6 µM for F7 EGF domain1 Publication
  2. KM=4 µM for GDP-fucose1 Publication
  1. Vmax=3 µmol/min/mg enzyme1 Publication

Pathwayi: protein glycosylation

This protein is involved in the pathway protein glycosylation, which is part of Protein modification.1 Publication
View all proteins of this organism that are known to be involved in the pathway protein glycosylation and in Protein modification.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei340SubstrateCombined sources1 Publication1

GO - Molecular functioni

  • fucosyltransferase activity Source: UniProtKB
  • peptide-O-fucosyltransferase activity Source: UniProtKB

GO - Biological processi

  • angiogenesis Source: Ensembl
  • embryo development Source: UniProtKB
  • fucose metabolic process Source: UniProtKB-KW
  • heart development Source: Ensembl
  • nervous system development Source: Ensembl
  • Notch signaling pathway Source: UniProtKB
  • O-glycan processing Source: UniProtKB
  • protein O-linked fucosylation Source: UniProtKB
  • protein O-linked glycosylation Source: UniProtKB
  • regulation of Notch signaling pathway Source: UniProtKB
  • regulation of transcription, DNA-templated Source: UniProtKB
  • somitogenesis Source: Ensembl

Keywordsi

Molecular functionGlycosyltransferase, Transferase
Biological processCarbohydrate metabolism, Fucose metabolism, Notch signaling pathway
LigandManganese

Enzyme and pathway databases

BRENDAi2.4.1.221. 2681.
ReactomeiR-HSA-1912399. Pre-NOTCH Processing in the Endoplasmic Reticulum.
SignaLinkiQ9H488.
SIGNORiQ9H488.
UniPathwayiUPA00378.

Protein family/group databases

CAZyiGT65. Glycosyltransferase Family 65.

Names & Taxonomyi

Protein namesi
Recommended name:
GDP-fucose protein O-fucosyltransferase 1 (EC:2.4.1.2211 Publication)
Alternative name(s):
Peptide-O-fucosyltransferase 1
Short name:
O-FucT-1
Gene namesi
Name:POFUT1
Synonyms:FUT12, KIAA0180
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

EuPathDBiHostDB:ENSG00000101346.11.
HGNCiHGNC:14988. POFUT1.

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Endoplasmic reticulum

Pathology & Biotechi

Involvement in diseasei

Dowling-Degos disease 2 (DDD2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal dominant genodermatosis. Affected individuals develop a postpubertal reticulate hyperpigmentation that is progressive and disfiguring, and small hyperkeratotic dark brown papules that affect mainly the flexures and great skin folds. Patients usually show no abnormalities of the hair or nails.
See also OMIM:615327

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi240R → A or C: Strongly impaired ability to activate NOTCH signaling. 1 Publication1
Mutagenesisi262M → T: No effect on ability to activate NOTCH signaling. 1 Publication1
Mutagenesisi356S → F: Abolishes ability to activate NOTCH signaling. 1 Publication1
Mutagenesisi366R → W: Strongly impaired ability to activate NOTCH signaling. 1 Publication1

Organism-specific databases

DisGeNETi23509.
MalaCardsiPOFUT1.
MIMi615327. phenotype.
OpenTargetsiENSG00000101346.
Orphaneti79145. Dowling-Degos disease.
PharmGKBiPA33495.

Polymorphism and mutation databases

BioMutaiPOFUT1.
DMDMi23396787.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 26Sequence analysisAdd BLAST26
ChainiPRO_000001214827 – 388GDP-fucose protein O-fucosyltransferase 1Add BLAST362

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi38 ↔ 40Combined sources1 Publication
Glycosylationi62N-linked (GlcNAc...) asparagineCombined sources1 Publication1
Disulfide bondi126 ↔ 140Combined sources1 Publication
Glycosylationi160N-linked (GlcNAc...) asparagine1 Publication1
Disulfide bondi249 ↔ 283Combined sources1 Publication
Disulfide bondi267 ↔ 354Combined sources1 Publication

Post-translational modificationi

N-glycosylated.1 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ9H488.
MaxQBiQ9H488.
PaxDbiQ9H488.
PeptideAtlasiQ9H488.
PRIDEiQ9H488.

PTM databases

iPTMnetiQ9H488.
PhosphoSitePlusiQ9H488.
SwissPalmiQ9H488.

Expressioni

Tissue specificityi

Highly expressed in heart, brain, placenta, lung, liver, skeletal muscle, kidney and pancreas.1 Publication

Gene expression databases

BgeeiENSG00000101346.
CleanExiHS_POFUT1.
GenevisibleiQ9H488. HS.

Organism-specific databases

HPAiHPA054519.
HPA059935.

Interactioni

Protein-protein interaction databases

BioGridi117056. 10 interactors.
IntActiQ9H488. 3 interactors.
STRINGi9606.ENSP00000364902.

Structurei

Secondary structure

1388
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi34 – 37Combined sources4
Beta strandi41 – 43Combined sources3
Helixi44 – 61Combined sources18
Beta strandi64 – 67Combined sources4
Beta strandi70 – 72Combined sources3
Beta strandi83 – 85Combined sources3
Helixi87 – 90Combined sources4
Beta strandi91 – 93Combined sources3
Helixi94 – 98Combined sources5
Beta strandi102 – 104Combined sources3
Helixi105 – 111Combined sources7
Helixi113 – 116Combined sources4
Helixi119 – 121Combined sources3
Beta strandi123 – 127Combined sources5
Helixi128 – 132Combined sources5
Beta strandi134 – 136Combined sources3
Beta strandi142 – 145Combined sources4
Helixi148 – 153Combined sources6
Turni154 – 156Combined sources3
Beta strandi161 – 165Combined sources5
Helixi172 – 174Combined sources3
Helixi175 – 181Combined sources7
Turni184 – 186Combined sources3
Beta strandi188 – 194Combined sources7
Helixi203 – 211Combined sources9
Helixi216 – 229Combined sources14
Beta strandi232 – 239Combined sources8
Helixi243 – 253Combined sources11
Turni262 – 264Combined sources3
Helixi265 – 268Combined sources4
Helixi272 – 274Combined sources3
Helixi280 – 283Combined sources4
Helixi287 – 301Combined sources15
Beta strandi304 – 312Combined sources9
Helixi316 – 322Combined sources7
Turni323 – 325Combined sources3
Beta strandi326 – 330Combined sources5
Helixi337 – 345Combined sources9
Beta strandi347 – 352Combined sources6
Helixi357 – 369Combined sources13
Beta strandi373 – 375Combined sources3
Beta strandi378 – 380Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
5UX6X-ray2.09A/B24-384[»]
5UXHX-ray2.41A/B24-384[»]
ProteinModelPortaliQ9H488.
SMRiQ9H488.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni44 – 46Substrate bindingCombined sources1 Publication3
Regioni238 – 240Substrate bindingCombined sources1 Publication3
Regioni357 – 358Substrate bindingCombined sources1 Publication2

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi385 – 388Prevents secretion from ERSequence analysis4

Sequence similaritiesi

Belongs to the glycosyltransferase 68 family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3849. Eukaryota.
ENOG410Y3JQ. LUCA.
GeneTreeiENSGT00390000015634.
HOGENOMiHOG000231651.
HOVERGENiHBG059976.
InParanoidiQ9H488.
KOiK03691.
OMAiGQSNHFI.
OrthoDBiEOG091G048B.
PhylomeDBiQ9H488.
TreeFamiTF314805.

Family and domain databases

InterProiView protein in InterPro
IPR019378. GDP-Fuc_O-FucTrfase.
PfamiView protein in Pfam
PF10250. O-FucT. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9H488-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MGAAAWARPL SVSFLLLLLP LPGMPAGSWD PAGYLLYCPC MGRFGNQADH
60 70 80 90 100
FLGSLAFAKL LNRTLAVPPW IEYQHHKPPF TNLHVSYQKY FKLEPLQAYH
110 120 130 140 150
RVISLEDFME KLAPTHWPPE KRVAYCFEVA AQRSPDKKTC PMKEGNPFGP
160 170 180 190 200
FWDQFHVSFN KSELFTGISF SASYREQWSQ RFSPKEHPVL ALPGAPAQFP
210 220 230 240 250
VLEEHRPLQK YMVWSDEMVK TGEAQIHAHL VRPYVGIHLR IGSDWKNACA
260 270 280 290 300
MLKDGTAGSH FMASPQCVGY SRSTAAPLTM TMCLPDLKEI QRAVKLWVRS
310 320 330 340 350
LDAQSVYVAT DSESYVPELQ QLFKGKVKVV SLKPEVAQVD LYILGQADHF
360 370 380
IGNCVSSFTA FVKRERDLQG RPSSFFGMDR PPKLRDEF
Length:388
Mass (Da):43,956
Last modified:March 1, 2001 - v1
Checksum:i3FACCCA434D02415
GO
Isoform 2 (identifier: Q9H488-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:194
Mass (Da):22,338
Checksum:i5ADE77CE45147644
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_049231322L → F. Corresponds to variant dbSNP:rs17268666Ensembl.1
Natural variantiVAR_049232348D → N. Corresponds to variant dbSNP:rs35259534Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_001809182 – 388FSPKE…LRDEF → RENHSCVTLLFPR in isoform 2. 1 PublicationAdd BLAST207

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS13198.1. [Q9H488-1]
CCDS13199.1. [Q9H488-2]
RefSeqiNP_056167.1. NM_015352.1. [Q9H488-1]
NP_758436.1. NM_172236.1. [Q9H488-2]
UniGeneiHs.472409.

Genome annotation databases

EnsembliENST00000375730; ENSP00000364882; ENSG00000101346. [Q9H488-2]
ENST00000375749; ENSP00000364902; ENSG00000101346. [Q9H488-1]
GeneIDi23509.
KEGGihsa:23509.
UCSCiuc002wxo.3. human. [Q9H488-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiOFUT1_HUMAN
AccessioniPrimary (citable) accession number: Q9H488
Secondary accession number(s): A8K4R8
, E1P5M4, Q14685, Q5W185, Q9BW76
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 19, 2002
Last sequence update: March 1, 2001
Last modified: September 27, 2017
This is version 150 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  7. SIMILARITY comments
    Index of protein domains and families