RFNG_HUMAN
ID RFNG_HUMAN Reviewed; 331 AA.
AC Q9Y644; O00588;
DT 10-JAN-2003, integrated into UniProtKB/Swiss-Prot.
DT 18-MAY-2010, sequence version 3.
DT 03-AUG-2022, entry version 155.
DE RecName: Full=Beta-1,3-N-acetylglucosaminyltransferase radical fringe;
DE EC=2.4.1.222;
DE AltName: Full=O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase;
GN Name=RFNG;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-191.
RX PubMed=10341080; DOI=10.1007/s003359901039;
RA Moran J.L., Johnston S.H., Rauskolb C., Bhalerao J., Bowcock A.M.,
RA Vogt T.F.;
RT "Genomic structure, mapping, and expression analysis of the mammalian
RT Lunatic, Manic, and Radical fringe genes.";
RL Mamm. Genome 10:535-541(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 141-331.
RX PubMed=9187150; DOI=10.1242/dev.124.11.2245;
RA Johnston S.H., Rauskolb C., Wilson R., Prabhakaran B., Irvine K.D.,
RA Vogt T.F.;
RT "A family of mammalian Fringe genes implicated in boundary determination
RT and the Notch pathway.";
RL Development 124:2245-2254(1997).
CC -!- FUNCTION: Glycosyltransferase that initiates the elongation of O-linked
CC fucose residues attached to EGF-like repeats in the extracellular
CC domain of Notch molecules. Modulates NOTCH1 activity by modifying O-
CC fucose residues at specific EGF-like domains resulting in enhancement
CC of NOTCH1 activation by DLL1 and JAG1. May be involved in limb
CC formation and in neurogenesis. {ECO:0000250|UniProtKB:O09009,
CC ECO:0000250|UniProtKB:O12972, ECO:0000250|UniProtKB:Q9R1U9}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-O-(alpha-L-fucosyl)-L-threonyl-[EGF-like domain protein] +
CC UDP-N-acetyl-alpha-D-glucosamine = 3-O-(N-acetyl-beta-D-glucosaminyl-
CC (1->3)-alpha-L-fucosyl)-L-threonyl-[EGF-like domain protein] + H(+) +
CC UDP; Xref=Rhea:RHEA:70531, Rhea:RHEA-COMP:17922, Rhea:RHEA-
CC COMP:17923, ChEBI:CHEBI:15378, ChEBI:CHEBI:57705, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:189631, ChEBI:CHEBI:189634; EC=2.4.1.222;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3-O-(alpha-L-fucosyl)-L-seryl-[EGF-like domain protein] + UDP-
CC N-acetyl-alpha-D-glucosamine = 3-O-(N-acetyl-beta-D-glucosaminyl-
CC (1->3)-alpha-L-fucosyl)-L-seryl-[EGF-like domain protein] + H(+) +
CC UDP; Xref=Rhea:RHEA:70511, Rhea:RHEA-COMP:17919, Rhea:RHEA-
CC COMP:17920, ChEBI:CHEBI:15378, ChEBI:CHEBI:57705, ChEBI:CHEBI:58223,
CC ChEBI:CHEBI:189632, ChEBI:CHEBI:189633; EC=2.4.1.222;
CC -!- COFACTOR:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; Evidence={ECO:0000250};
CC -!- SUBCELLULAR LOCATION: Golgi apparatus membrane {ECO:0000305}; Single-
CC pass type II membrane protein {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 31 family.
CC {ECO:0000305}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AC135056; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF108139; AAD34321.1; -; Genomic_DNA.
DR EMBL; U94353; AAC51359.1; -; mRNA.
DR CCDS; CCDS32773.1; -.
DR RefSeq; NP_002908.1; NM_002917.1.
DR AlphaFoldDB; Q9Y644; -.
DR SMR; Q9Y644; -.
DR BioGRID; 111918; 5.
DR STRING; 9606.ENSP00000307971; -.
DR CAZy; GT31; Glycosyltransferase Family 31.
DR GlyGen; Q9Y644; 2 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q9Y644; -.
DR PhosphoSitePlus; Q9Y644; -.
DR BioMuta; RFNG; -.
DR DMDM; 296452991; -.
DR EPD; Q9Y644; -.
DR jPOST; Q9Y644; -.
DR MassIVE; Q9Y644; -.
DR MaxQB; Q9Y644; -.
DR PaxDb; Q9Y644; -.
DR PeptideAtlas; Q9Y644; -.
DR PRIDE; Q9Y644; -.
DR ProteomicsDB; 86598; -.
DR Antibodypedia; 2622; 117 antibodies from 21 providers.
DR DNASU; 5986; -.
DR Ensembl; ENST00000310496.9; ENSP00000307971.4; ENSG00000169733.12.
DR GeneID; 5986; -.
DR KEGG; hsa:5986; -.
DR MANE-Select; ENST00000310496.9; ENSP00000307971.4; NM_002917.2; NP_002908.1.
DR UCSC; uc002kdj.3; human.
DR CTD; 5986; -.
DR DisGeNET; 5986; -.
DR GeneCards; RFNG; -.
DR HGNC; HGNC:9974; RFNG.
DR HPA; ENSG00000169733; Low tissue specificity.
DR MIM; 602578; gene.
DR neXtProt; NX_Q9Y644; -.
DR OpenTargets; ENSG00000169733; -.
DR PharmGKB; PA34343; -.
DR VEuPathDB; HostDB:ENSG00000169733; -.
DR eggNOG; ENOG502QV30; Eukaryota.
DR GeneTree; ENSGT00940000160801; -.
DR HOGENOM; CLU_056611_0_1_1; -.
DR InParanoid; Q9Y644; -.
DR OMA; RKYHKTR; -.
DR OrthoDB; 826272at2759; -.
DR PhylomeDB; Q9Y644; -.
DR TreeFam; TF324207; -.
DR BRENDA; 2.4.1.222; 2681.
DR PathwayCommons; Q9Y644; -.
DR Reactome; R-HSA-1912420; Pre-NOTCH Processing in Golgi.
DR SignaLink; Q9Y644; -.
DR SIGNOR; Q9Y644; -.
DR BioGRID-ORCS; 5986; 17 hits in 1078 CRISPR screens.
DR ChiTaRS; RFNG; human.
DR GenomeRNAi; 5986; -.
DR Pharos; Q9Y644; Tdark.
DR PRO; PR:Q9Y644; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q9Y644; protein.
DR Bgee; ENSG00000169733; Expressed in right lobe of liver and 152 other tissues.
DR ExpressionAtlas; Q9Y644; baseline and differential.
DR Genevisible; Q9Y644; HS.
DR GO; GO:0005576; C:extracellular region; NAS:UniProtKB.
DR GO; GO:0030173; C:integral component of Golgi membrane; IEA:InterPro.
DR GO; GO:0008375; F:acetylglucosaminyltransferase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0033829; F:O-fucosylpeptide 3-beta-N-acetylglucosaminyltransferase activity; IBA:GO_Central.
DR GO; GO:0009887; P:animal organ morphogenesis; NAS:UniProtKB.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0007389; P:pattern specification process; IEA:InterPro.
DR GO; GO:0045747; P:positive regulation of Notch signaling pathway; IEA:Ensembl.
DR GO; GO:0032092; P:positive regulation of protein binding; IEA:Ensembl.
DR GO; GO:0008593; P:regulation of Notch signaling pathway; ISS:UniProtKB.
DR InterPro; IPR017374; Fringe.
DR InterPro; IPR003378; Fringe-like.
DR Pfam; PF02434; Fringe; 1.
DR PIRSF; PIRSF038073; B-acetylgalactosaminyltfrase; 1.
PE 2: Evidence at transcript level;
KW Developmental protein; Differentiation; Disulfide bond; Glycoprotein;
KW Glycosyltransferase; Golgi apparatus; Manganese; Membrane; Metal-binding;
KW Neurogenesis; Reference proteome; Signal-anchor; Transferase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..331
FT /note="Beta-1,3-N-acetylglucosaminyltransferase radical
FT fringe"
FT /id="PRO_0000219185"
FT TOPO_DOM 1..6
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 7..29
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 30..331
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 34..54
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 34..53
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 237
FT /evidence="ECO:0000250"
FT BINDING 74
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 147
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT BINDING 148
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250"
FT BINDING 261
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250"
FT CARBOHYD 113
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 114..125
FT /evidence="ECO:0000250"
FT DISULFID 143..207
FT /evidence="ECO:0000250"
FT DISULFID 311..320
FT /evidence="ECO:0000250"
FT CONFLICT 288
FT /note="H -> Q (in Ref. 3; AAC51359)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 331 AA; 36424 MW; 986270FFA7C13573 CRC64;
MSRARGALCR ACLALAAALA ALLLLPLPLP RAPAPARTPA PAPRAPPSRP AAPSLRPDDV
FIAVKTTRKN HGPRLRLLLR TWISRARQQT FIFTDGDDPE LELQGGDRVI NTNCSAVRTR
QALCCKMSVE YDKFIESGRK WFCHVDDDNY VNARSLLHLL SSFSPSQDVY LGRPSLDHPI
EATERVQGGR TVTTVKFWFA TGGAGFCLSR GLALKMSPWA SLGSFMSTAE QVRLPDDCTV
GYIVEGLLGA RLLHSPLFHS HLENLQRLPP DTLLQQVTLS HGGPENPHNV VNVAGGFSLH
QDPTRFKSIH CLLYPDTDWC PRQKQGAPTS R
