Q9H488 · OFUT1_HUMAN
- ProteinGDP-fucose protein O-fucosyltransferase 1
- GenePOFUT1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids388 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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).
Catalytic activity
- GDP-beta-L-fucose + L-seryl-[protein] = 3-O-(alpha-L-fucosyl)-L-seryl-[protein] + GDP + H+This reaction proceeds in the forward direction.
Kinetics
KM | SUBSTRATE | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|---|
6 μM | F7 EGF domain | |||||
4 μM | GDP-fucose |
Vmax | pH | TEMPERATURE[C] | NOTES | EVIDENCE | |
---|---|---|---|---|---|
3 μmol/min/mg |
Pathway
Protein modification; protein glycosylation.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 43-46 | substrate | ||||
Sequence: RFGN | ||||||
Binding site | 238-240 | substrate | ||||
Sequence: HLR | ||||||
Binding site | 340 | substrate | ||||
Sequence: D | ||||||
Binding site | 357-358 | substrate | ||||
Sequence: SF |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum | |
Cellular Component | membrane | |
Molecular Function | fucosyltransferase activity | |
Molecular Function | peptide-O-fucosyltransferase activity | |
Biological Process | angiogenesis | |
Biological Process | fucose metabolic process | |
Biological Process | heart development | |
Biological Process | nervous system development | |
Biological Process | Notch signaling pathway | |
Biological Process | O-glycan processing | |
Biological Process | protein O-linked fucosylation | |
Biological Process | protein O-linked glycosylation | |
Biological Process | regulation of DNA-templated transcription | |
Biological Process | regulation of Notch signaling pathway | |
Biological Process | somitogenesis |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameGDP-fucose protein O-fucosyltransferase 1
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9H488
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Disease & Variants
Involvement in disease
Dowling-Degos disease 2 (DDD2)
- Note
- 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 alsoMIM:615327
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 240 | Strongly impaired ability to activate NOTCH signaling. | ||||
Sequence: R → A or C | ||||||
Mutagenesis | 262 | No effect on ability to activate NOTCH signaling. | ||||
Sequence: M → T | ||||||
Natural variant | VAR_049231 | 322 | in dbSNP:rs17268666 | |||
Sequence: L → F | ||||||
Natural variant | VAR_049232 | 348 | in dbSNP:rs35259534 | |||
Sequence: D → N | ||||||
Mutagenesis | 356 | Abolishes ability to activate NOTCH signaling. | ||||
Sequence: S → F | ||||||
Mutagenesis | 366 | Strongly impaired ability to activate NOTCH signaling. | ||||
Sequence: R → W |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 420 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for signal, chain, disulfide bond, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Signal | 1-26 | |||||
Sequence: MGAAAWARPLSVSFLLLLLPLPGMPA | ||||||
Chain | PRO_0000012148 | 27-388 | GDP-fucose protein O-fucosyltransferase 1 | |||
Sequence: GSWDPAGYLLYCPCMGRFGNQADHFLGSLAFAKLLNRTLAVPPWIEYQHHKPPFTNLHVSYQKYFKLEPLQAYHRVISLEDFMEKLAPTHWPPEKRVAYCFEVAAQRSPDKKTCPMKEGNPFGPFWDQFHVSFNKSELFTGISFSASYREQWSQRFSPKEHPVLALPGAPAQFPVLEEHRPLQKYMVWSDEMVKTGEAQIHAHLVRPYVGIHLRIGSDWKNACAMLKDGTAGSHFMASPQCVGYSRSTAAPLTMTMCLPDLKEIQRAVKLWVRSLDAQSVYVATDSESYVPELQQLFKGKVKVVSLKPEVAQVDLYILGQADHFIGNCVSSFTAFVKRERDLQGRPSSFFGMDRPPKLRDEF | ||||||
Disulfide bond | 38↔40 | |||||
Sequence: CPC | ||||||
Glycosylation | 62 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 126↔140 | |||||
Sequence: CFEVAAQRSPDKKTC | ||||||
Glycosylation | 160 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Disulfide bond | 249↔283 | |||||
Sequence: CAMLKDGTAGSHFMASPQCVGYSRSTAAPLTMTMC | ||||||
Disulfide bond | 267↔354 | |||||
Sequence: CVGYSRSTAAPLTMTMCLPDLKEIQRAVKLWVRSLDAQSVYVATDSESYVPELQQLFKGKVKVVSLKPEVAQVDLYILGQADHFIGNC |
Post-translational modification
N-glycosylated.
Keywords
- PTM
Proteomic databases
PTM databases
Structure
Family & Domains
Features
Showing features for motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Motif | 385-388 | Prevents secretion from ER | ||||
Sequence: RDEF |
Sequence similarities
Belongs to the glycosyltransferase 65 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
- Sequence processingThe displayed sequence is further processed into a mature form.
This entry describes 2 isoforms produced by Alternative splicing.
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.
- Name1
- Length388
- Mass (Da)43,956
- Last updated2001-03-01 v1
- Checksum3FACCCA434D02415
Q9H488-2
- Name2
- Differences from canonical
- 182-388: FSPKEHPVLALPGAPAQFPVLEEHRPLQKYMVWSDEMVKTGEAQIHAHLVRPYVGIHLRIGSDWKNACAMLKDGTAGSHFMASPQCVGYSRSTAAPLTMTMCLPDLKEIQRAVKLWVRSLDAQSVYVATDSESYVPELQQLFKGKVKVVSLKPEVAQVDLYILGQADHFIGNCVSSFTAFVKRERDLQGRPSSFFGMDRPPKLRDEF → RENHSCVTLLFPR
Computationally mapped potential isoform sequences
There are 2 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A9L9PY15 | A0A9L9PY15_HUMAN | POFUT1 | 206 | ||
A0A9L9PX68 | A0A9L9PX68_HUMAN | POFUT1 | 78 |
Features
Showing features for alternative sequence.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_001809 | 182-388 | in isoform 2 | |||
Sequence: FSPKEHPVLALPGAPAQFPVLEEHRPLQKYMVWSDEMVKTGEAQIHAHLVRPYVGIHLRIGSDWKNACAMLKDGTAGSHFMASPQCVGYSRSTAAPLTMTMCLPDLKEIQRAVKLWVRSLDAQSVYVATDSESYVPELQQLFKGKVKVVSLKPEVAQVDLYILGQADHFIGNCVSSFTAFVKRERDLQGRPSSFFGMDRPPKLRDEF → RENHSCVTLLFPR |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF375884 EMBL· GenBank· DDBJ | AAL09576.1 EMBL· GenBank· DDBJ | mRNA | ||
D80002 EMBL· GenBank· DDBJ | BAA11497.2 EMBL· GenBank· DDBJ | mRNA | ||
AL121897 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AK291033 EMBL· GenBank· DDBJ | BAF83722.1 EMBL· GenBank· DDBJ | mRNA | ||
CH471077 EMBL· GenBank· DDBJ | EAW76383.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471077 EMBL· GenBank· DDBJ | EAW76384.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
CH471077 EMBL· GenBank· DDBJ | EAW76385.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC000582 EMBL· GenBank· DDBJ | AAH00582.1 EMBL· GenBank· DDBJ | mRNA |