Q8NES3 (LFNG_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Beta-1,3-N-acetylglucosaminyltransferase lunatic fringe
EC=2.4.1.222

Alternative name(s):
O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase

Gene names

Name:

LFNG

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	379 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Glycosyltransferase that initiates the elongation of O-linked fucose residues attached to EGF-like repeats in the extracellular domain of Notch molecules. Decreases the binding of JAGGED1 to NOTCH2 but not that of DELTA1. Essential mediator of somite segmentation and patterning By similarity.
Catalytic activity	Transfers a beta-D-GlcNAc residue from UDP-D-GlcNAc to the fucose residue of a fucosylated protein acceptor.
Cofactor	Manganese By similarity.
Subcellular location	Golgi apparatus membrane; Single-pass type II membrane protein By similarity.
Post-translational modification	A soluble form may be derived from the membrane form by proteolytic processing Potential.
Involvement in disease	Spondylocostal dysostosis 3 (SCDO3) [MIM:609813]: An autosomal recessive 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8
Sequence similarities	Belongs to the glycosyltransferase 31 family.

Ontologies

Keywords
Cellular component	Golgi apparatus Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Dwarfism
Domain	Signal-anchor Transmembrane Transmembrane helix
Ligand	Manganese Metal-binding
Molecular function	Developmental protein Glycosyltransferase Transferase
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Notch signaling pathway Traceable author statement. Source: Reactome compartment pattern specification Inferred from electronic annotation. Source: Compara female meiosis Inferred from electronic annotation. Source: Compara organ morphogenesis Non-traceable author statement PubMed 10341080. Source: UniProtKB ovarian follicle development Inferred from electronic annotation. Source: Compara positive regulation of Notch signaling pathway Inferred from electronic annotation. Source: Compara positive regulation of protein binding Inferred from electronic annotation. Source: Compara
Cellular_component	extracellular region Non-traceable author statement PubMed 10341080. Source: UniProtKB integral to Golgi membrane Inferred from electronic annotation. Source: InterPro
Molecular_function	O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase activity Inferred from electronic annotation. Source: EC metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 4 isoforms produced by alternative splicing. [Align] [Select]

Note: Experimental confirmation may be lacking for some isoforms.

Isoform 1 (identifier: Q8NES3-1)

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: Q8NES3-2)

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

Isoform 3 (identifier: Q8NES3-3)

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

Isoform 4 (identifier: Q8NES3-4)

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.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 379	379	Beta-1,3-N-acetylglucosaminyltransferase lunatic fringe		PRO_0000219176
Regions
	Topological domain	1 – 8	8	Cytoplasmic Potential
	Transmembrane	9 – 29	21	Helical; Signal-anchor for type II membrane protein; Potential
	Topological domain	30 – 379	350	Lumenal Potential
Sites
	Active site	290	1	By similarity
	Metal binding	202	1	Manganese By similarity
	Metal binding	314	1	Manganese By similarity
	Binding site	129	1	Substrate By similarity
	Binding site	201	1	Substrate By similarity
	Site	86 – 87	2	Cleavage; by furin-like protease Potential
Amino acid modifications
	Glycosylation	167	1	N-linked (GlcNAc...) Potential
	Disulfide bond	168 ↔ 179		By similarity
	Disulfide bond	197 ↔ 260		By similarity
	Disulfide bond	364 ↔ 373		By similarity
Natural variations
	Alternative sequence	1 – 129	129	Missing in isoform 2.		VSP_001792
	Alternative sequence	1 – 73	73	MLKRC…RDVHS → MDEQTGRLRLDTYCMSAKQI WAWSKCSGRLWDEHMKWMEG WTDRWTDGWMDGWMDEWSPT PALRSYGGGLSQQ in isoform 4.		VSP_044850
	Alternative sequence	74 – 144	71	Missing in isoform 4.		VSP_044851
	Alternative sequence	130 – 145	16	LDLLL…HKEMT → MTPGRCCLAADIQVET in isoform 2.		VSP_001793
	Alternative sequence	359 – 361	3	FRS → WGN in isoform 3.		VSP_001794
	Alternative sequence	362 – 379	18	Missing in isoform 3.		VSP_001795
	Natural variant	38	1	G → R. Ref.9		VAR_046785
	Natural variant	188	1	F → L in SCDO3; not localized to the correct compartment of the cell; unable to modulate Notch signaling in a cell-based assay; enzymatically inactive. Ref.8		VAR_025850
	Natural variant	346	1	V → M. Ref.9		VAR_046786
Experimental info
	Sequence conflict	104	1	R → A in AAF07187. Ref.5
	Sequence conflict	212	1	R → L in AAC51360. Ref.3
	Sequence conflict	221	1	R → L in AAC51360. Ref.3
	Sequence conflict	297	1	V → M in BAG53248. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 10, 2003. Version 2. Checksum: 4400ECA731B36B45	FASTA	379	41,773
	10 20 30 40 50 60 MLKRCGRRLL LALAGALLAC LLVLTADPPP PPLPAERGRR ALRSLAGPAG AAPAPGLGAA 70 80 90 100 110 120 AAAPGALVRD VHSLSEYFSL LTRARRDAGP PPGAAPRPAD GHPRPLAEPL APRDVFIAVK 130 140 150 160 170 180 TTKKFHRARL DLLLETWISR HKEMTFIFTD GEDEALARHT GNVVITNCSA AHSRQALSCK 190 200 210 220 230 240 MAVEYDRFIE SGRKWFCHVD DDNYVNLRAL LRLLASYPHT RDVYVGKPSL DRPIQAMERV 250 260 270 280 290 300 SENKVRPVHF WFATGGAGFC ISRGLALKMS PWASGGHFMN TAERIRLPDD CTIGYIVEAL 310 320 330 340 350 360 LGVPLIRSGL FHSHLENLQQ VPTSELHEQV TLSYGMFENK RNAVHVKGPF SVEADPSRFR 370 SIHCHLYPDT PWCPRTAIF
	Isoform 2 [UniParc]. Checksum: E09162F8B0016412	FASTA	250	28,151
	10 20 30 40 50 60 MTPGRCCLAA DIQVETFIFT DGEDEALARH TGNVVITNCS AAHSRQALSC KMAVEYDRFI 70 80 90 100 110 120 ESGRKWFCHV DDDNYVNLRA LLRLLASYPH TRDVYVGKPS LDRPIQAMER VSENKVRPVH 130 140 150 160 170 180 FWFATGGAGF CISRGLALKM SPWASGGHFM NTAERIRLPD DCTIGYIVEA LLGVPLIRSG 190 200 210 220 230 240 LFHSHLENLQ QVPTSELHEQ VTLSYGMFEN KRNAVHVKGP FSVEADPSRF RSIHCHLYPD 250 TPWCPRTAIF
	Isoform 3 [UniParc]. Checksum: AC5CE1662524395B	FASTA	361	39,588
	10 20 30 40 50 60 MLKRCGRRLL LALAGALLAC LLVLTADPPP PPLPAERGRR ALRSLAGPAG AAPAPGLGAA 70 80 90 100 110 120 AAAPGALVRD VHSLSEYFSL LTRARRDAGP PPGAAPRPAD GHPRPLAEPL APRDVFIAVK 130 140 150 160 170 180 TTKKFHRARL DLLLETWISR HKEMTFIFTD GEDEALARHT GNVVITNCSA AHSRQALSCK 190 200 210 220 230 240 MAVEYDRFIE SGRKWFCHVD DDNYVNLRAL LRLLASYPHT RDVYVGKPSL DRPIQAMERV 250 260 270 280 290 300 SENKVRPVHF WFATGGAGFC ISRGLALKMS PWASGGHFMN TAERIRLPDD CTIGYIVEAL 310 320 330 340 350 360 LGVPLIRSGL FHSHLENLQQ VPTSELHEQV TLSYGMFENK RNAVHVKGPF SVEADPSRWG N
	Isoform 4 [UniParc]. Checksum: 2FE290EDD113DD28	FASTA	308	35,266
	10 20 30 40 50 60 MDEQTGRLRL DTYCMSAKQI WAWSKCSGRL WDEHMKWMEG WTDRWTDGWM DGWMDEWSPT 70 80 90 100 110 120 PALRSYGGGL SQQTFIFTDG EDEALARHTG NVVITNCSAA HSRQALSCKM AVEYDRFIES 130 140 150 160 170 180 GRKWFCHVDD DNYVNLRALL RLLASYPHTR DVYVGKPSLD RPIQAMERVS ENKVRPVHFW 190 200 210 220 230 240 FATGGAGFCI SRGLALKMSP WASGGHFMNT AERIRLPDDC TIGYIVEALL GVPLIRSGLF 250 260 270 280 290 300 HSHLENLQQV PTSELHEQVT LSYGMFENKR NAVHVKGPFS VEADPSRFRS IHCHLYPDTP WCPRTAIF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"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 4).
[2]	"The DNA sequence of human chromosome 7." Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K. Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]	"A family of mammalian Fringe genes implicated in boundary determination and the Notch pathway." Johnston S.H., Rauskolb C., Wilson R., Prabhakaran B., Irvine K.D., Vogt T.F. Development 124:2245-2254(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 105-361 (ISOFORM 3).
[4]	"Clock regulatory elements control cyclic expression of Lunatic fringe during somitogenesis." Cole S.E., Levorse J.M., Tilghman S.M., Vogt T.F. Dev. Cell 3:75-84(2002) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-144 (ISOFORM 1).
[5]	"Homo sapiens fringe gene homolog." Holloway J., Blumberg H., Jelinek L., Whitmore T., Jaspers S., Gross J., Haldeman B., Taft D., O'Hara P. Submitted (NOV-1999) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 104-361 (ISOFORM 3).
[6]	"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: Kidney.
[7]	"Manic fringe and lunatic fringe modify different sites of the Notch2 extracellular region, resulting in different signaling modulation." Shimizu K., Chiba S., Saito T., Kumano K., Takahashi T., Hirai H. J. Biol. Chem. 276:25753-25758(2001) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[8]	"Mutation of the LUNATIC FRINGE gene in humans causes spondylocostal dysostosis with a severe vertebral phenotype." Sparrow D.B., Chapman G., Wouters M.A., Whittock N.V., Ellard S., Fatkin D., Turnpenny P.D., Kusumi K., Sillence D., Dunwoodie S.L. Am. J. Hum. Genet. 78:28-37(2006) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT SCDO3 LEU-188, CHARACTERIZATION OF VARIANT SCDO3 LEU-188.
[9]	"Mutations in the MESP2 gene cause spondylothoracic dysostosis/Jarcho-Levin syndrome." Cornier A.S., Staehling-Hampton K., Delventhal K.M., Saga Y., Caubet J.-F., Sasaki N., Ellard S., Young E., Ramirez N., Carlo S.E., Torres J., Emans J.B., Turnpenny P.D., Pourquie O. Am. J. Hum. Genet. 82:1334-1341(2008) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ARG-38 AND MET-346.
+	Additional computationally mapped references.

Web resources

GGDB

GlycoGene database

GeneReviews

Functional Glycomics Gateway - GTase

Beta-1,3-N-acetylglucosaminyltransferase lunatic fringe

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00219477. IPI00455739. IPI00472104. IPI00892667.
RefSeq	NP_001035257.1. NM_001040167.1. NP_001035258.1. NM_001040168.1. NP_001159827.1. NM_001166355.1. NP_002295.1. NM_002304.2.
UniGene	Hs.159142.
3D structure databases
ProteinModelPortal	Q8NES3.
ModBase	Search...
Protein-protein interaction databases
STRING	9606.ENSP00000222725.
Protein family/group databases
CAZy	GT31. Glycosyltransferase Family 31.
PTM databases
PhosphoSite	Q8NES3.
Polymorphism databases
DMDM	27734417.
Proteomic databases
PaxDb	Q8NES3.
PRIDE	Q8NES3.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000222725; ENSP00000222725; ENSG00000106003. ENST00000338732; ENSP00000343095; ENSG00000106003. ENST00000359574; ENSP00000352579; ENSG00000106003. ENST00000402045; ENSP00000384786; ENSG00000106003. ENST00000402506; ENSP00000385764; ENSG00000106003.
GeneID	3955.
KEGG	hsa:3955.
UCSC	uc003smf.3. human. uc003smg.3. human. uc021zyx.1. human.
Organism-specific databases
CTD	3955.
GeneCards	GC07P002552.
HGNC	HGNC:6560. LFNG.
MIM	602576. gene. 609813. phenotype.
neXtProt	NX_Q8NES3.
Orphanet	2311. Autosomal recessive spondylocostal dysostosis.
PharmGKB	PA30336.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG70217.
HOGENOM	HOG000046678.
HOVERGEN	HBG007986.
InParanoid	Q8NES3.
KO	K05948.
OMA	SENKMHP.
PhylomeDB	Q8NES3.
Enzyme and pathway databases
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
ArrayExpress	Q8NES3.
Bgee	Q8NES3.
CleanEx	HS_LFNG.
Genevestigator	Q8NES3.
Family and domain databases
InterPro	IPR017374. Fringe. IPR003378. Fringe-like. [Graphical view]
Pfam	PF02434. Fringe. 1 hit. [Graphical view]
PIRSF	PIRSF038073. B-acetylgalactosaminyltfrase. 1 hit.
ProtoNet	Search...
Other
ChiTaRS	LFNG. human.
GenomeRNAi	3955.
NextBio	15517.
SOURCE	Search...

Entry information

Entry name

LFNG_HUMAN

Accession

Primary (citable) accession number: Q8NES3
Secondary accession number(s): B3KTY6 , B5MCR5, O00589, Q96C39, Q9UJW5

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 10, 2003
Last sequence update:	January 10, 2003
Last modified:	May 1, 2013
This is version 99 of the entry and version 2 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.