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Protein

Beta-1,3-N-acetylglucosaminyltransferase lunatic fringe

Gene

LFNG

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

Functioni

Glycosyltransferase that initiates the elongation of O-linked fucose residues attached to EGF-like repeats in the extracellular domain of Notch molecules. Modulates NOTCH1 activity by modifying O-fucose residues at specific EGF-like domains resulting in inhibition of NOTCH1 activation by JAG1 and enhancement of NOTCH1 activation by DLL1 via an increase in its binding to DLL1 (By similarity). Decreases the binding of JAG1 to NOTCH2 but not that of DLL1 (PubMed:11346656). Essential mediator of somite segmentation and patterning (By similarity).By similarity1 Publication

Catalytic activityi

Transfers a beta-D-GlcNAc residue from UDP-D-GlcNAc to the fucose residue of a fucosylated protein acceptor.

Cofactori

Mn2+By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei129SubstrateBy similarity1
Binding sitei201SubstrateBy similarity1
Metal bindingi202ManganeseBy similarity1
Active sitei290By similarity1
Metal bindingi314ManganeseBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein, Glycosyltransferase, Transferase
LigandManganese, Metal-binding

Enzyme and pathway databases

ReactomeiR-HSA-1912420. Pre-NOTCH Processing in Golgi.
SignaLinkiQ8NES3.
SIGNORiQ8NES3.

Protein family/group databases

CAZyiGT31. Glycosyltransferase Family 31.

Names & Taxonomyi

Protein namesi
Recommended name:
Beta-1,3-N-acetylglucosaminyltransferase lunatic fringe (EC:2.4.1.222)
Alternative name(s):
O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase
Gene namesi
Name:LFNG
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000106003.12.
HGNCiHGNC:6560. LFNG.

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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 8CytoplasmicSequence analysis8
Transmembranei9 – 29Helical; Signal-anchor for type II membrane proteinSequence analysisAdd BLAST21
Topological domaini30 – 379LumenalSequence analysisAdd BLAST350

Keywords - Cellular componenti

Golgi apparatus, Membrane

Pathology & Biotechi

Involvement in diseasei

Spondylocostal dysostosis 3, autosomal recessive (SCDO3)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA condition of variable severity associated with vertebral and rib segmentation defects. The main skeletal malformations include fusion of vertebrae, hemivertebrae, fusion of certain ribs, and other rib malformations. Deformity of the chest and spine (severe scoliosis, kyphoscoliosis and lordosis) is a natural consequence of the malformation and leads to a dwarf-like appearance. As the thorax is small, infants frequently have respiratory insufficiency and repeated respiratory infections resulting in life-threatening complications in the first year of life.
See also OMIM:609813
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_025850188F → L in SCDO3; not localized to the correct compartment of the cell; unable to modulate Notch signaling in a cell-based assay; enzymatically inactive. 1 PublicationCorresponds to variant dbSNP:rs104894024Ensembl.1

Keywords - Diseasei

Disease mutation, Dwarfism

Organism-specific databases

DisGeNETi3955.
GeneReviewsiLFNG.
MalaCardsiLFNG.
MIMi609813. phenotype.
OpenTargetsiENSG00000106003.
Orphaneti2311. Autosomal recessive spondylocostal dysostosis.
PharmGKBiPA30336.

Polymorphism and mutation databases

BioMutaiLFNG.
DMDMi27734417.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002191761 – 379Beta-1,3-N-acetylglucosaminyltransferase lunatic fringeAdd BLAST379

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Glycosylationi167N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi168 ↔ 179By similarity
Disulfide bondi197 ↔ 260By similarity
Disulfide bondi364 ↔ 373By similarity

Post-translational modificationi

A soluble form may be derived from the membrane form by proteolytic processing.Curated

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei86 – 87Cleavage; by furin-like proteaseSequence analysis2

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ8NES3.
MaxQBiQ8NES3.
PaxDbiQ8NES3.
PeptideAtlasiQ8NES3.
PRIDEiQ8NES3.

PTM databases

iPTMnetiQ8NES3.
PhosphoSitePlusiQ8NES3.

Expressioni

Gene expression databases

BgeeiENSG00000106003.
CleanExiHS_LFNG.
ExpressionAtlasiQ8NES3. baseline and differential.
GenevisibleiQ8NES3. HS.

Organism-specific databases

HPAiHPA069130.

Interactioni

Protein-protein interaction databases

BioGridi110146. 4 interactors.
STRINGi9606.ENSP00000222725.

Structurei

3D structure databases

ProteinModelPortaliQ8NES3.
SMRiQ8NES3.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the glycosyltransferase 31 family.Curated

Keywords - Domaini

Signal-anchor, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiENOG410II9W. Eukaryota.
ENOG410XS8Y. LUCA.
GeneTreeiENSGT00390000009913.
HOGENOMiHOG000046678.
HOVERGENiHBG007986.
InParanoidiQ8NES3.
KOiK05948.
OMAiPHTQDVY.
OrthoDBiEOG091G08XO.
PhylomeDBiQ8NES3.
TreeFamiTF324207.

Family and domain databases

InterProiView protein in InterPro
IPR017374. Fringe.
IPR003378. Fringe-like.
PfamiView protein in Pfam
PF02434. Fringe. 1 hit.
PIRSFiPIRSF038073. B-acetylgalactosaminyltfrase. 1 hit.

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Experimental confirmation may be lacking for some isoforms.
Isoform 1 (identifier: Q8NES3-1) [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
MLKRCGRRLL LALAGALLAC LLVLTADPPP PPLPAERGRR ALRSLAGPAG
60 70 80 90 100
AAPAPGLGAA AAAPGALVRD VHSLSEYFSL LTRARRDAGP PPGAAPRPAD
110 120 130 140 150
GHPRPLAEPL APRDVFIAVK TTKKFHRARL DLLLETWISR HKEMTFIFTD
160 170 180 190 200
GEDEALARHT GNVVITNCSA AHSRQALSCK MAVEYDRFIE SGRKWFCHVD
210 220 230 240 250
DDNYVNLRAL LRLLASYPHT RDVYVGKPSL DRPIQAMERV SENKVRPVHF
260 270 280 290 300
WFATGGAGFC ISRGLALKMS PWASGGHFMN TAERIRLPDD CTIGYIVEAL
310 320 330 340 350
LGVPLIRSGL FHSHLENLQQ VPTSELHEQV TLSYGMFENK RNAVHVKGPF
360 370
SVEADPSRFR SIHCHLYPDT PWCPRTAIF
Length:379
Mass (Da):41,773
Last modified:January 10, 2003 - v2
Checksum:i4400ECA731B36B45
GO
Isoform 2 (identifier: Q8NES3-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-129: Missing.
     130-145: LDLLLETWISRHKEMT → MTPGRCCLAADIQVET

Show »
Length:250
Mass (Da):28,151
Checksum:iE09162F8B0016412
GO
Isoform 3 (identifier: Q8NES3-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     359-361: FRS → WGN
     362-379: Missing.

Show »
Length:361
Mass (Da):39,588
Checksum:iAC5CE1662524395B
GO
Isoform 4 (identifier: Q8NES3-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-73: MLKRCGRRLL...PGALVRDVHS → MDEQTGRLRL...RSYGGGLSQQ
     74-144: Missing.

Note: No experimental confirmation available.
Show »
Length:308
Mass (Da):35,266
Checksum:i2FE290EDD113DD28
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti104R → A in AAF07187 (Ref. 5) Curated1
Sequence conflicti212R → L in AAC51360 (PubMed:9187150).Curated1
Sequence conflicti221R → L in AAC51360 (PubMed:9187150).Curated1
Sequence conflicti297V → M in BAG53248 (PubMed:14702039).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04678538G → R1 PublicationCorresponds to variant dbSNP:rs71647812Ensembl.1
Natural variantiVAR_025850188F → L in SCDO3; not localized to the correct compartment of the cell; unable to modulate Notch signaling in a cell-based assay; enzymatically inactive. 1 PublicationCorresponds to variant dbSNP:rs104894024Ensembl.1
Natural variantiVAR_046786346V → M1 PublicationCorresponds to variant dbSNP:rs71647813Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0017921 – 129Missing in isoform 2. 1 PublicationAdd BLAST129
Alternative sequenceiVSP_0448501 – 73MLKRC…RDVHS → MDEQTGRLRLDTYCMSAKQI WAWSKCSGRLWDEHMKWMEG WTDRWTDGWMDGWMDEWSPT PALRSYGGGLSQQ in isoform 4. 1 PublicationAdd BLAST73
Alternative sequenceiVSP_04485174 – 144Missing in isoform 4. 1 PublicationAdd BLAST71
Alternative sequenceiVSP_001793130 – 145LDLLL…HKEMT → MTPGRCCLAADIQVET in isoform 2. 1 PublicationAdd BLAST16
Alternative sequenceiVSP_001794359 – 361FRS → WGN in isoform 3. 2 Publications3
Alternative sequenceiVSP_001795362 – 379Missing in isoform 3. 2 PublicationsAdd BLAST18

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK096284 mRNA. Translation: BAG53248.1.
AC092488 Genomic DNA. No translation available.
U94354 mRNA. Translation: AAC51360.1.
AY124582 Genomic DNA. Translation: AAM93542.1.
AF193612 mRNA. Translation: AAF07187.1.
BC014851 mRNA. Translation: AAH14851.1.
CCDSiCCDS34586.1. [Q8NES3-3]
CCDS34587.1. [Q8NES3-1]
CCDS55081.1. [Q8NES3-4]
CCDS55082.1. [Q8NES3-2]
RefSeqiNP_001035257.1. NM_001040167.1. [Q8NES3-1]
NP_001035258.1. NM_001040168.1. [Q8NES3-3]
NP_001159827.1. NM_001166355.1. [Q8NES3-4]
NP_002295.1. NM_002304.2. [Q8NES3-2]
UniGeneiHs.159142.

Genome annotation databases

EnsembliENST00000222725; ENSP00000222725; ENSG00000106003. [Q8NES3-1]
ENST00000338732; ENSP00000343095; ENSG00000106003. [Q8NES3-2]
ENST00000359574; ENSP00000352579; ENSG00000106003. [Q8NES3-3]
ENST00000402045; ENSP00000384786; ENSG00000106003. [Q8NES3-2]
ENST00000402506; ENSP00000385764; ENSG00000106003. [Q8NES3-4]
GeneIDi3955.
KEGGihsa:3955.
UCSCiuc003smf.4. human. [Q8NES3-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiLFNG_HUMAN
AccessioniPrimary (citable) accession number: Q8NES3
Secondary accession number(s): B3KTY6
, B5MCR5, O00589, Q96C39, Q9UJW5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 10, 2003
Last sequence update: January 10, 2003
Last modified: October 25, 2017
This is version 142 of the entry and version 2 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

Complete proteome, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: 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. SIMILARITY comments
    Index of protein domains and families