ID FUT3_HUMAN Reviewed; 361 AA. AC P21217; B5U7U9; B5U7V0; Q32NE7; Q99448; Q99449; DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot. DT 24-JAN-2024, sequence version 2. DT 27-MAR-2024, entry version 213. DE RecName: Full=3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase FUT3 {ECO:0000305}; DE EC=2.4.1.65 {ECO:0000269|PubMed:1977660, ECO:0000269|PubMed:7721776}; DE AltName: Full=4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase; DE EC=2.4.1.152 {ECO:0000269|PubMed:29593094}; DE AltName: Full=Alpha-3-fucosyltransferase FUT3 {ECO:0000305}; DE EC=2.4.1.- {ECO:0000269|PubMed:1977660}; DE AltName: Full=Blood group Lewis alpha-4-fucosyltransferase; DE Short=Lewis FT; DE AltName: Full=Fucosyltransferase 3; DE AltName: Full=Fucosyltransferase III; DE Short=FucT-III; GN Name=FUT3 {ECO:0000312|HGNC:HGNC:4014}; Synonyms=FT3B, LE; 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 [MRNA], VARIANTS TRP-68 AND THR-105, CATALYTIC RP ACTIVITY, FUNCTION, AND TOPOLOGY. RX PubMed=1977660; DOI=10.1101/gad.4.8.1288; RA Kukowska-Latallo J.F., Larsen R.D., Nair R.P., Lowe J.B.; RT "A cloned human cDNA determines expression of a mouse stage-specific RT embryonic antigen and the Lewis blood group RT alpha(1,3/1,4)fucosyltransferase."; RL Genes Dev. 4:1288-1303(1990). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LE(-) ARG-20; SER-170 AND RP ALA-336, AND VARIANTS TRP-68 AND THR-105. RX PubMed=8240337; DOI=10.1006/bbrc.1993.2295; RA Nishihara S., Yazawa S., Iwasaki H., Nakazato M., Kudo T., Ando T., RA Narimatsu H.; RT "Alpha (1,3/1,4)fucosyltransferase (FucT-III) gene is inactivated by a RT single amino acid substitution in Lewis histo-blood type negative RT individuals."; RL Biochem. Biophys. Res. Commun. 196:624-631(1993). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], VARIANTS TRP-68 AND THR-105, AND TISSUE RP SPECIFICITY. RC TISSUE=Liver; RX PubMed=7650030; DOI=10.1074/jbc.270.34.20112; RA Cameron H.S., Szczepaniak D., Weston B.W.; RT "Expression of human chromosome 19p alpha(1,3)-fucosyltransferase genes in RT normal tissues. Alternative splicing, polyadenylation, and isoforms."; RL J. Biol. Chem. 270:20112-20122(1995). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANTS TRP-68 AND THR-105. RC TISSUE=Squamous cell carcinoma; RA Rahim I., Schmidt L.R., Wahl D., Drayson E., Maslanik W., Stranahan P.L., RA Pettijohn D.E.; RT "Isolation and expression of human alpha (1,3/1,4) fucosyltransferase."; RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT THR-105. RC TISSUE=Blood; RA Matzhold E.M.; RT "Allele frequencies of fucosyltransferases 1, 2, and 3 of Styrian blood RT donors."; RL Submitted (SEP-2008) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LE(-) ARG-20; ASN-162; SER-170; RP ARG-223 AND MET-270, VARIANTS SER-5; CYS-160; MET-325 AND GLN-327, AND RP VARIANTS TRP-68 AND THR-105. RG SeattleSNPs variation discovery resource; RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANTS TRP-68 AND THR-105. RC TISSUE=Colon, and Lung; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP CATALYTIC ACTIVITY, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AND RP GLYCOSYLATION. RX PubMed=7721776; DOI=10.1074/jbc.270.15.8712; RA de Vries T., Srnka C.A., Palcic M.M., Swiedler S.J., van den Eijnden D.H., RA Macher B.A.; RT "Acceptor specificity of different length constructs of human recombinant RT alpha 1,3/4-fucosyltransferases. Replacement of the stem region and the RT transmembrane domain of fucosyltransferase V by protein A results in an RT enzyme with GDP-fucose hydrolyzing activity."; RL J. Biol. Chem. 270:8712-8722(1995). RN [10] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=11058871; RX DOI=10.1002/1097-0215(20001115)88:4<558::aid-ijc7>3.0.co;2-b; RA Aubert M., Panicot-Dubois L., Crotte C., Sbarra V., Lombardo D., RA Sadoulet M.O., Mas E.; RT "Peritoneal colonization by human pancreatic cancer cells is inhibited by RT antisense FUT3 sequence."; RL Int. J. Cancer 88:558-565(2000). RN [11] RP CATALYTIC ACTIVITY, AND FUNCTION. RX PubMed=12668675; DOI=10.1074/jbc.m211034200; RA Tsuchida A., Okajima T., Furukawa K., Ando T., Ishida H., Yoshida A., RA Nakamura Y., Kannagi R., Kiso M., Furukawa K.; RT "Synthesis of disialyl Lewis a (Le(a)) structure in colon cancer cell lines RT by a sialyltransferase, ST6GalNAc VI, responsible for the synthesis of RT alpha-series gangliosides."; RL J. Biol. Chem. 278:22787-22794(2003). RN [12] RP FUNCTION. RX PubMed=27453266; RA Cai Y.J., Zheng X.F., Lu C.H., Jiang Q., Liu Q., Xin Y.H.; RT "Effect of FUT3 gene silencing with miRNA on proliferation, invasion and RT migration abilities of human KATO-III gastric cancer cell line."; RL Cell. Mol. Biol. 62:15-20(2016). RN [13] RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY. RX PubMed=29593094; DOI=10.1074/jbc.ra117.000775; RA Mondal N., Dykstra B., Lee J., Ashline D.J., Reinhold V.N., Rossi D.J., RA Sackstein R.; RT "Distinct human alpha(1,3)-fucosyltransferases drive Lewis-X/sialyl Lewis-X RT assembly in human cells."; RL J. Biol. Chem. 293:7300-7314(2018). RN [14] RP VARIANT LE(-) MET-105. RX PubMed=8240322; DOI=10.1006/bbrc.1993.2280; RA Elmgren A., Rydberg L., Larson G.; RT "Genotypic heterogeneity among Lewis negative individuals."; RL Biochem. Biophys. Res. Commun. 196:515-520(1993). RN [15] RP VARIANTS LE(-) ARG-20 AND SER-170. RX PubMed=8219240; RA Koda Y., Kimura H., Mekada E.; RT "Analysis of Lewis fucosyltransferase genes from the human gastric mucosa RT of Lewis-positive and -negative individuals."; RL Blood 82:2915-2919(1993). RN [16] RP VARIANTS LE(-) ARG-20 AND LYS-356. RX PubMed=8063716; DOI=10.1016/s0021-9258(17)31919-1; RA Mollicone R., Reguigne I., Kelly R.J., Fletcher A., Watt J., Chatfield S., RA Aziz A., Cameron H.S., Weston B.W., Lowe J.B., Oriol R.; RT "Molecular basis for Lewis alpha(1,3/1,4)-fucosyltransferase gene RT deficiency (FUT3) found in Lewis-negative Indonesian pedigrees."; RL J. Biol. Chem. 269:20987-20994(1994). RN [17] RP VARIANT LE(-) LYS-356. RX PubMed=7961897; DOI=10.1016/s0021-9258(19)62041-7; RA Nishihara S., Narimatsu H., Iwasaki H., Yazawa S., Akamatsu S., Ando T., RA Seno T., Narimatsu I.; RT "Molecular genetic analysis of the human Lewis histo-blood group system."; RL J. Biol. Chem. 269:29271-29278(1994). RN [18] RP VARIANTS LE(-) ARG-20; ARG-68; MET-105 AND LYS-356. RX PubMed=8801770; DOI=10.1111/j.1423-0410.1996.tb01300.x; RA Elmgren A., Boerjeson C., Svensson L., Rydberg L., Larson G.; RT "DNA sequencing and screening for point mutations in the human Lewis 'FUT3' RT gene enables molecular genotyping of the human Lewis blood group system."; RL Vox Sang. 70:97-103(1996). RN [19] RP VARIANTS LE(-) ARG-68 AND MET-105. RX PubMed=9268337; DOI=10.1074/jbc.272.35.21994; RA Elmgren A., Mollicone R., Costache M., Boerjeson C., Oriol R., RA Harrington J., Larson G.; RT "Significance of individual point mutations, T202C and C314T, in the human RT Lewis 'FUT3' gene for expression of Lewis antigens by the human RT alpha'1,3/1,4'-fucosyltransferase, Fuc-TIII."; RL J. Biol. Chem. 272:21994-21998(1997). RN [20] RP VARIANTS LE(-) ASN-162; ARG-223 AND MET-270, AND CHARACTERIZATION OF RP VARIANTS LE(-) ASN-162; ARG-223 AND MET-270. RX PubMed=10211701; DOI=10.1023/a:1006981724233; RA Pang H., Koda Y., Soejima M., Kimura H.; RT "Significance of each of three missense mutations, G484A, G667A, and G808A, RT present in an inactive allele of the human Lewis gene (FUT3) for RT alpha(1,3/1,4)fucosyltransferase inactivation."; RL Glycoconj. J. 15:961-967(1998). RN [21] RP VARIANTS LE(+) LYS-102 AND ALA-124, AND VARIANTS LE(-) ASN-162; ARG-223 AND RP MET-270. RX PubMed=9703429; DOI=10.1007/s004390050760; RA Pang H., Liu Y., Koda Y., Soejima M., Jia J., Schlaphoff T., du Toit E.D., RA Kimura H.; RT "Five novel missense mutations of the Lewis gene 'FUT3' in African 'Xhosa' RT and Caucasian populations in South Africa."; RL Hum. Genet. 102:675-680(1998). CC -!- FUNCTION: Catalyzes the transfer of L-fucose, from a guanosine CC diphosphate-beta-L-fucose, to both the subterminal N-acetyl glucosamine CC (GlcNAc) of type 1 chain (beta-D-Gal-(1->3)-beta-D-GlcNAc) glycolipids CC and oligosaccharides via an alpha(1,4) linkage, and the subterminal CC glucose (Glc) or GlcNAc of type 2 chain (beta-D-Gal-(1->4)-beta-D- CC GlcNAc) oligosaccharides via an alpha(1,3) linkage, independently of CC the presence of terminal alpha-L-fucosyl-(1,2) moieties on the terminal CC galactose of these acceptors (PubMed:12668675, PubMed:1977660, CC PubMed:11058871). Through its catalytic activity, participates in the CC synthesis of antigens of the Lewis blood group system, i.e. Lewis a CC (Le(a)), lewis b (Le(b)), Lewis x/SSEA-1 (Le(x)) and lewis y (Le(y)) CC antigens (PubMed:12668675, PubMed:1977660, PubMed:11058871). Also CC catalyzes the transfer of L-fucose to subterminal GlcNAc of sialyl- and CC disialyl-lactotetraosylceramide to produce sialyl Lewis a (sLe(a)) and CC disialyl Lewis a via an alpha(1,4) linkage and therefore may regulate CC cell surface sLe(a) expression and consequently regulates adhesive CC properties to E-selectin, cell proliferation and migration CC (PubMed:12668675, PubMed:11058871, PubMed:27453266). Catalyzes the CC transfer of an L-fucose to 3'-sialyl-N-acetyllactosamine by an CC alpha(1,3) linkage, which allows the formation of sialyl-Lewis x CC structure and therefore may regulate the sialyl-Lewis x surface antigen CC expression and consequently adhesive properties to E-selectin CC (PubMed:11058871, PubMed:29593094). Prefers type 1 chain over type 2 CC acceptors (PubMed:7721776). Type 1 tetrasaccharide is a better acceptor CC than type 1 disaccharide suggesting that a beta anomeric configuration CC of GlcNAc in the substrate is preferred (PubMed:7721776). Lewis- CC positive (Le(+)) individuals have an active enzyme while Lewis-negative CC (Le(-)) individuals have an inactive enzyme (PubMed:1977660). CC {ECO:0000269|PubMed:11058871, ECO:0000269|PubMed:12668675, CC ECO:0000269|PubMed:1977660, ECO:0000269|PubMed:27453266, CC ECO:0000269|PubMed:7721776}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a beta-D-galactosyl-(1->3)-N-acetyl-beta-D-glucosaminyl CC derivative + GDP-beta-L-fucose = a beta-D-galactosyl-(1->3)-[alpha-L- CC fucosyl-(1->4)]-N-acetyl-beta-D-glucosaminyl derivative + GDP + H(+); CC Xref=Rhea:RHEA:23628, ChEBI:CHEBI:15378, ChEBI:CHEBI:57273, CC ChEBI:CHEBI:58189, ChEBI:CHEBI:133506, ChEBI:CHEBI:140304; CC EC=2.4.1.65; Evidence={ECO:0000269|PubMed:1977660, CC ECO:0000269|PubMed:7721776}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23629; CC Evidence={ECO:0000305|PubMed:1977660}; CC -!- CATALYTIC ACTIVITY: CC Reaction=an N-acetyl-alpha-neuraminyl-(2->3)-beta-D-galactosyl-(1->4)- CC N-acetyl-beta-D-glucosaminyl derivative + GDP-beta-L-fucose = an CC alpha-Neu5Ac-(2->3)-beta-D-Gal-(1->4)-[alpha-L-Fuc-(1->3)]-beta-D- CC GlcNAc derivative + GDP + H(+); Xref=Rhea:RHEA:56076, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57273, ChEBI:CHEBI:58189, CC ChEBI:CHEBI:136545, ChEBI:CHEBI:139509; CC Evidence={ECO:0000269|PubMed:29593094}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:56077; CC Evidence={ECO:0000305|PubMed:29593094}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl CC derivative + GDP-beta-L-fucose = a beta-D-galactosyl-(1->4)-[alpha-L- CC fucosyl-(1->3)]-N-acetyl-beta-D-glucosaminyl derivative + GDP + H(+); CC Xref=Rhea:RHEA:14257, ChEBI:CHEBI:15378, ChEBI:CHEBI:57273, CC ChEBI:CHEBI:58189, ChEBI:CHEBI:133507, ChEBI:CHEBI:137941; CC EC=2.4.1.152; Evidence={ECO:0000269|PubMed:29593094}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14258; CC Evidence={ECO:0000305|PubMed:29593094}; CC -!- CATALYTIC ACTIVITY: CC Reaction=an alpha-Neu5Ac-(2->3)-beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->3)- CC beta-D-Gal-(1->4)-[alpha-L-Fuc-(1->3)]-beta-D-GlcNAc derivative + CC GDP-beta-L-fucose = an alpha-Neu5Ac-(2->3)-beta-D-Gal-(1->4)-[alpha- CC L-Fuc-(1->3)]-beta-D-GlcNAc-(1->3)-beta-D-Gal-(1->4)-[alpha-L-Fuc- CC (1->3)]-beta-D-GlcNAc derivative + GDP + H(+); Xref=Rhea:RHEA:52864, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57273, ChEBI:CHEBI:58189, CC ChEBI:CHEBI:145342, ChEBI:CHEBI:145343; CC Evidence={ECO:0000269|PubMed:29593094}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:52865; CC Evidence={ECO:0000305|PubMed:29593094}; CC -!- CATALYTIC ACTIVITY: CC Reaction=GDP-beta-L-fucose + Lc4Cer = a lactoside III(4)-a-Fuc-Lc4Cer + CC GDP + H(+); Xref=Rhea:RHEA:48824, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57273, ChEBI:CHEBI:58189, ChEBI:CHEBI:90800, CC ChEBI:CHEBI:90811; Evidence={ECO:0000269|PubMed:7721776}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48825; CC Evidence={ECO:0000305|PubMed:7721776}; CC -!- CATALYTIC ACTIVITY: CC Reaction=a beta-D-Gal-(1->3)-beta-D-GlcNAc-(1->3)-beta-D-Gal-(1->4)- CC beta-D-Glc-(1<->1')-Cer(d18:1(4E)) + GDP-beta-L-fucose = a III(4)-a- CC Fuc-Lc4Cer(d18:1(4E)) + GDP + H(+); Xref=Rhea:RHEA:48328, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17292, ChEBI:CHEBI:57273, CC ChEBI:CHEBI:58189, ChEBI:CHEBI:90292; CC Evidence={ECO:0000269|PubMed:7721776}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48329; CC Evidence={ECO:0000305|PubMed:7721776}; CC -!- CATALYTIC ACTIVITY: CC Reaction=GDP-beta-L-fucose + N-acetyl-alpha-neuraminosyl-(2->3)-beta-D- CC galactosyl-(1->3)-[N-acetyl-alpha-neuraminosyl-(2->6)]-N-acetyl-beta- CC D-glucosaminyl-(1->3)-beta-D-galactosyl-(1->4)-beta-D-glucosyl- CC (1<->1')-N-acyl-sphing-4-enine = GDP + H(+) + N-acetyl-alpha- CC neuraminosyl-(2->3)-beta-D-galactosyl-(1->3)-alpha-L-fucosyl-(1->4)- CC [N-acetyl-alpha-neuraminosyl-(2->6)-N-acetyl-beta-D-glucosaminyl- CC (1->3)]-beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1')-N-acyl- CC sphing-4-enine; Xref=Rhea:RHEA:47892, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57273, ChEBI:CHEBI:58189, ChEBI:CHEBI:88079, CC ChEBI:CHEBI:88089; Evidence={ECO:0000269|PubMed:12668675}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47893; CC Evidence={ECO:0000305|PubMed:12668675}; CC -!- CATALYTIC ACTIVITY: CC Reaction=GDP-beta-L-fucose + N-acetyl-alpha-neuraminosyl-(2->3)-beta-D- CC galactosyl-(1->3)-N-acetyl-beta-D-glucosaminyl-(1->3)-beta-D- CC galactosyl-(1->4)-beta-D-glucosyl-(1<->1')-N-acyl-sphing-4-enine = CC GDP + H(+) + N-acetyl-alpha-neuraminosyl-(2->3)-beta-D-galactosyl- CC (1->3)-alpha-L-fucosyl-(1->4)-[N-acetyl-beta-D-glucosaminyl-(1->3)]- CC beta-D-galactosyl-(1->4)-beta-D-glucosyl-(1<->1')-N-acyl-sphing-4- CC enine; Xref=Rhea:RHEA:47888, ChEBI:CHEBI:15378, ChEBI:CHEBI:57273, CC ChEBI:CHEBI:58189, ChEBI:CHEBI:88073, ChEBI:CHEBI:88088; CC Evidence={ECO:0000269|PubMed:12668675}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47889; CC Evidence={ECO:0000305|PubMed:12668675}; CC -!- CATALYTIC ACTIVITY: CC Reaction=beta-D-galactosyl-(1->3)-N-acetyl-D-glucosamine + GDP-beta-L- CC fucose = beta-D-galactosyl-(1->3)-[alpha-L-fucosyl-(1->4)]-N-acetyl- CC D-glucosamine + GDP + H(+); Xref=Rhea:RHEA:62844, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:27707, ChEBI:CHEBI:57273, ChEBI:CHEBI:58189, CC ChEBI:CHEBI:62265; Evidence={ECO:0000269|PubMed:1977660, CC ECO:0000269|PubMed:7721776}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62845; CC Evidence={ECO:0000305|PubMed:7721776}; CC -!- CATALYTIC ACTIVITY: CC Reaction=alpha-L-Fuc-(1->2)-beta-D-Gal-(1->3)-D-GlcNAc + GDP-beta-L- CC fucose = alpha-L-Fuc-(1->2)-beta-D-Gal-(1->3)-[alpha-L-Fuc-(1->4)]-D- CC GlcNAc + GDP + H(+); Xref=Rhea:RHEA:62896, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57273, ChEBI:CHEBI:58189, ChEBI:CHEBI:59440, CC ChEBI:CHEBI:62259; Evidence={ECO:0000269|PubMed:1977660}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62897; CC Evidence={ECO:0000305|PubMed:1977660}; CC -!- CATALYTIC ACTIVITY: CC Reaction=alpha-L-Fuc-(1->2)-beta-D-Gal-(1->4)-D-GlcNAc + GDP-beta-L- CC fucose = alpha-L-Fuc-(1->2)-beta-D-Gal-(1->4)-[alpha-L-Fuc-(1->3)]-D- CC GlcNAc + GDP + H(+); Xref=Rhea:RHEA:62900, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57273, ChEBI:CHEBI:58189, ChEBI:CHEBI:62263, CC ChEBI:CHEBI:62507; Evidence={ECO:0000269|PubMed:1977660}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62901; CC Evidence={ECO:0000305|PubMed:1977660}; CC -!- CATALYTIC ACTIVITY: CC Reaction=beta-D-galactosyl-(1->4)-N-acetyl-D-glucosamine + GDP-beta-L- CC fucose = beta-D-galactosyl-(1->4)-[alpha-L-fucosyl-(1->3)]-N-acetyl- CC D-glucosamine + GDP + H(+); Xref=Rhea:RHEA:62824, ChEBI:CHEBI:15378, CC ChEBI:CHEBI:57273, ChEBI:CHEBI:58189, ChEBI:CHEBI:60152, CC ChEBI:CHEBI:62287; Evidence={ECO:0000269|PubMed:1977660}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62825; CC Evidence={ECO:0000305|PubMed:1977660}; CC -!- CATALYTIC ACTIVITY: CC Reaction=GDP-beta-L-fucose + lactose = beta-D-galactosyl-(1->4)-[alpha- CC L-fucosyl-(1->3)]-D-glucose + GDP + H(+); Xref=Rhea:RHEA:62888, CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17716, ChEBI:CHEBI:57273, CC ChEBI:CHEBI:58189, ChEBI:CHEBI:90065; CC Evidence={ECO:0000269|PubMed:1977660}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62889; CC Evidence={ECO:0000305|PubMed:1977660}; CC -!- CATALYTIC ACTIVITY: CC Reaction=an alpha-Neu5Ac-(2->3)-beta-D-Gal-(1->3)-D-GlcNAc derivative + CC GDP-beta-L-fucose = an alpha-Neu5Ac-(2->3)-beta-D-Gal-(1->3)-[alpha- CC L-Fuc-(1->4)]-beta-D-GlcNAc derivative + GDP + H(+); CC Xref=Rhea:RHEA:62904, ChEBI:CHEBI:15378, ChEBI:CHEBI:57273, CC ChEBI:CHEBI:58189, ChEBI:CHEBI:146021, ChEBI:CHEBI:146022; CC Evidence={ECO:0000269|PubMed:11058871}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62905; CC Evidence={ECO:0000305|PubMed:11058871}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1 mM for beta-D-Gal-(1->3)-beta-D-GlcNAc-O-CH(2)(8)-COOCH(3) CC {ECO:0000269|PubMed:7721776}; CC KM=0.1 mM for fucalpha1->2Galbeta1->3GlcNAcbeta-O-CH(2)(8)-COOCH(3) CC {ECO:0000269|PubMed:7721776}; CC KM=0.58 mM for NeuAca2->3GAlb1->3GlcNAcB-O-CH(2)(8)-COOCH(3) CC {ECO:0000269|PubMed:7721776}; CC -!- PATHWAY: Protein modification; protein glycosylation. CC {ECO:0000269|PubMed:1977660, ECO:0000269|PubMed:29593094}. CC -!- INTERACTION: CC P21217; P58499: FAM3B; NbExp=3; IntAct=EBI-12839380, EBI-12955347; CC P21217; Q96IW7: SEC22A; NbExp=3; IntAct=EBI-12839380, EBI-8652744; CC P21217; Q96JW4: SLC41A2; NbExp=3; IntAct=EBI-12839380, EBI-10290130; CC P21217; Q5BVD1: TTMP; NbExp=3; IntAct=EBI-12839380, EBI-10243654; CC P21217; A5PKU2: TUSC5; NbExp=3; IntAct=EBI-12839380, EBI-11988865; CC -!- SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane; Single- CC pass type II membrane protein {ECO:0000269|PubMed:1977660}. CC Note=Membrane-bound form in trans cisternae of Golgi. CC -!- TISSUE SPECIFICITY: Highly expressed in stomach, colon, small CC intestine, lung and kidney and to a lesser extent in salivary gland, CC bladder, uterus and liver. {ECO:0000269|PubMed:7650030}. CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:7721776}. CC -!- POLYMORPHISM: Genetic variations in FUT3 define the Lewis blood group CC system (LE) [MIM:618983]. FUT3 catalyzes the addition of fucose to CC precursor polysaccharides in the last step of Lewis antigen CC biosynthesis. Variations in this gene are responsible for the majority CC of Lewis antigen-negative phenotypes (Le(-)). CC {ECO:0000269|PubMed:10211701, ECO:0000269|PubMed:7961897, CC ECO:0000269|PubMed:8240322, ECO:0000269|PubMed:8240337, CC ECO:0000269|PubMed:8801770, ECO:0000269|PubMed:9268337}. CC -!- SIMILARITY: Belongs to the glycosyltransferase 10 family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=dbRBC/BGMUT; Note=Blood group antigen gene mutation CC database; CC URL="https://www.ncbi.nlm.nih.gov/gv/mhc/xslcgi.cgi?cmd=bgmut/systems_info&system=lewis"; CC -!- WEB RESOURCE: Name=SeattleSNPs; CC URL="http://pga.gs.washington.edu/data/fut3/"; CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - GTase; CC Note=Fucosyltransferase 3; CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_600"; 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; X53578; CAA37641.1; -; mRNA. DR EMBL; U27326; AAC50185.1; -; mRNA. DR EMBL; U27327; AAC50186.1; -; mRNA. DR EMBL; U27328; AAC50187.1; -; mRNA. DR EMBL; D89324; BAA13941.1; -; Genomic_DNA. DR EMBL; D89325; BAA13942.1; -; Genomic_DNA. DR EMBL; AF131913; AAD33514.1; -; mRNA. DR EMBL; FM210024; CAR64692.1; -; Genomic_DNA. DR EMBL; FM210025; CAR64693.1; -; Genomic_DNA. DR EMBL; AY870341; AAW34365.1; -; Genomic_DNA. DR EMBL; AC024592; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC074836; AAH74836.1; -; mRNA. DR EMBL; BC074837; AAH74837.1; -; mRNA. DR EMBL; BC108675; AAI08676.1; -; mRNA. DR CCDS; CCDS12153.1; -. DR PIR; A36669; A36669. DR RefSeq; NP_000140.1; NM_000149.3. DR RefSeq; NP_001091108.1; NM_001097639.1. DR RefSeq; NP_001091109.1; NM_001097640.1. DR RefSeq; NP_001091110.1; NM_001097641.1. DR RefSeq; XP_011526167.1; XM_011527865.1. DR RefSeq; XP_011526168.1; XM_011527866.1. DR RefSeq; XP_011526169.1; XM_011527867.1. DR AlphaFoldDB; P21217; -. DR SMR; P21217; -. DR BioGRID; 108801; 97. DR IntAct; P21217; 21. DR STRING; 9606.ENSP00000305603; -. DR ChEMBL; CHEMBL3269; -. DR SwissLipids; SLP:000001370; -. DR CAZy; GT10; Glycosyltransferase Family 10. DR GlyCosmos; P21217; 2 sites, No reported glycans. DR GlyGen; P21217; 2 sites. DR iPTMnet; P21217; -. DR PhosphoSitePlus; P21217; -. DR BioMuta; FUT3; -. DR DMDM; 121137; -. DR EPD; P21217; -. DR jPOST; P21217; -. DR MassIVE; P21217; -. DR MaxQB; P21217; -. DR PaxDb; 9606-ENSP00000305603; -. DR PeptideAtlas; P21217; -. DR PRIDE; P21217; -. DR ProteomicsDB; 53853; -. DR Pumba; P21217; -. DR Antibodypedia; 11767; 598 antibodies from 36 providers. DR DNASU; 2525; -. DR Ensembl; ENST00000303225.12; ENSP00000305603.5; ENSG00000171124.14. DR Ensembl; ENST00000458379.7; ENSP00000416443.1; ENSG00000171124.14. DR Ensembl; ENST00000589620.6; ENSP00000465804.1; ENSG00000171124.14. DR Ensembl; ENST00000589918.5; ENSP00000468123.1; ENSG00000171124.14. DR Ensembl; ENST00000709634.1; ENSP00000517811.1; ENSG00000292063.1. DR Ensembl; ENST00000709635.1; ENSP00000517812.1; ENSG00000292063.1. DR Ensembl; ENST00000709636.1; ENSP00000517813.1; ENSG00000292063.1. DR Ensembl; ENST00000709637.1; ENSP00000517814.1; ENSG00000292063.1. DR GeneID; 2525; -. DR KEGG; hsa:2525; -. DR MANE-Select; ENST00000709635.1; ENSP00000517812.1; NM_001097639.3; NP_001091108.3. DR UCSC; uc002mdj.3; human. DR AGR; HGNC:4014; -. DR CTD; 2525; -. DR DisGeNET; 2525; -. DR GeneCards; FUT3; -. DR HGNC; HGNC:4014; FUT3. DR HPA; ENSG00000171124; Tissue enhanced (esophagus, intestine, retina, salivary gland). DR MalaCards; FUT3; -. DR MIM; 111100; gene. DR MIM; 618983; phenotype. DR neXtProt; NX_P21217; -. DR OpenTargets; ENSG00000171124; -. DR PharmGKB; PA28430; -. DR VEuPathDB; HostDB:ENSG00000171124; -. DR eggNOG; KOG2619; Eukaryota. DR GeneTree; ENSGT00940000163389; -. DR HOGENOM; CLU_032075_4_1_1; -. DR InParanoid; P21217; -. DR OrthoDB; 1331128at2759; -. DR PhylomeDB; P21217; -. DR TreeFam; TF316348; -. DR BioCyc; MetaCyc:HS10249-MONOMER; -. DR BRENDA; 2.4.1.65; 2681. DR PathwayCommons; P21217; -. DR Reactome; R-HSA-9037629; Lewis blood group biosynthesis. DR Reactome; R-HSA-975578; Reactions specific to the complex N-glycan synthesis pathway. DR SignaLink; P21217; -. DR SIGNOR; P21217; -. DR UniPathway; UPA00378; -. DR BioGRID-ORCS; 2525; 6 hits in 1139 CRISPR screens. DR ChiTaRS; FUT3; human. DR GeneWiki; Fucosyltransferase_3; -. DR GenomeRNAi; 2525; -. DR Pharos; P21217; Tbio. DR PRO; PR:P21217; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; P21217; Protein. DR Bgee; ENSG00000171124; Expressed in lower esophagus mucosa and 149 other cell types or tissues. DR ExpressionAtlas; P21217; baseline and differential. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0032580; C:Golgi cisterna membrane; IEA:UniProtKB-SubCell. DR GO; GO:0000139; C:Golgi membrane; TAS:Reactome. DR GO; GO:0016020; C:membrane; IDA:BHF-UCL. DR GO; GO:0017060; F:3-galactosyl-N-acetylglucosaminide 4-alpha-L-fucosyltransferase activity; IDA:UniProtKB. DR GO; GO:0017083; F:4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase activity; IDA:UniProtKB. DR GO; GO:0046920; F:alpha-(1->3)-fucosyltransferase activity; IDA:BHF-UCL. DR GO; GO:0008417; F:fucosyltransferase activity; IDA:BHF-UCL. DR GO; GO:0009988; P:cell-cell recognition; IC:BHF-UCL. DR GO; GO:0006672; P:ceramide metabolic process; IDA:BHF-UCL. DR GO; GO:0036065; P:fucosylation; IDA:UniProtKB. DR GO; GO:0043413; P:macromolecule glycosylation; IDA:BHF-UCL. DR GO; GO:0009312; P:oligosaccharide biosynthetic process; IDA:BHF-UCL. DR GO; GO:0009311; P:oligosaccharide metabolic process; IDA:UniProtKB. DR GO; GO:0022409; P:positive regulation of cell-cell adhesion; IMP:UniProtKB. DR GO; GO:0006487; P:protein N-linked glycosylation; IDA:UniProtKB. DR GO; GO:0006493; P:protein O-linked glycosylation; IDA:UniProtKB. DR GO; GO:0030334; P:regulation of cell migration; IMP:UniProtKB. DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:UniProtKB. DR Gene3D; 3.40.50.11660; Glycosyl transferase family 10, C-terminal domain; 1. DR InterPro; IPR031481; Glyco_tran_10_N. DR InterPro; IPR001503; Glyco_trans_10. DR InterPro; IPR038577; GT10-like_C_sf. DR PANTHER; PTHR11929:SF165; 3-GALACTOSYL-N-ACETYLGLUCOSAMINIDE 4-ALPHA-L-FUCOSYLTRANSFERASE FUT3; 1. DR PANTHER; PTHR11929; ALPHA- 1,3 -FUCOSYLTRANSFERASE; 1. DR Pfam; PF17039; Glyco_tran_10_N; 1. DR Pfam; PF00852; Glyco_transf_10; 1. DR SUPFAM; SSF53756; UDP-Glycosyltransferase/glycogen phosphorylase; 1. DR Genevisible; P21217; HS. PE 1: Evidence at protein level; KW Blood group antigen; Glycoprotein; Glycosyltransferase; Golgi apparatus; KW Lipid metabolism; Membrane; Reference proteome; Signal-anchor; Transferase; KW Transmembrane; Transmembrane helix. FT CHAIN 1..361 FT /note="3-galactosyl-N-acetylglucosaminide 4-alpha-L- FT fucosyltransferase FUT3" FT /id="PRO_0000221096" FT TOPO_DOM 1..15 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 16..34 FT /note="Helical; Signal-anchor for type II membrane protein" FT /evidence="ECO:0000255, ECO:0000269|PubMed:1977660" FT TOPO_DOM 35..361 FT /note="Lumenal" FT /evidence="ECO:0000255" FT REGION 39..58 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 44..58 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT CARBOHYD 154 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000305" FT CARBOHYD 185 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000305" FT VARIANT 5 FT /note="G -> S (in dbSNP:rs28362458)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_022200" FT VARIANT 20 FT /note="L -> R (in Le(-) individuals; dbSNP:rs28362459)" FT /evidence="ECO:0000269|PubMed:8063716, FT ECO:0000269|PubMed:8219240, ECO:0000269|PubMed:8240337, FT ECO:0000269|PubMed:8801770, ECO:0000269|Ref.6" FT /id="VAR_003426" FT VARIANT 68 FT /note="R -> W (in dbSNP:rs812936)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:1977660, ECO:0000269|PubMed:7650030, FT ECO:0000269|PubMed:8240337, ECO:0000269|Ref.4, FT ECO:0000269|Ref.6" FT /id="VAR_007959" FT VARIANT 102 FT /note="Q -> K (in Le(+) individuals; dbSNP:rs59796499)" FT /evidence="ECO:0000269|PubMed:9703429" FT /id="VAR_007960" FT VARIANT 105 FT /note="M -> T (in dbSNP:rs778986)" FT /evidence="ECO:0000269|PubMed:15489334, FT ECO:0000269|PubMed:1977660, ECO:0000269|PubMed:7650030, FT ECO:0000269|PubMed:8240337, ECO:0000269|Ref.4, FT ECO:0000269|Ref.5, ECO:0000269|Ref.6" FT /id="VAR_003427" FT VARIANT 124 FT /note="S -> A (in Le(+) individuals; dbSNP:rs1175404919)" FT /evidence="ECO:0000269|PubMed:9703429" FT /id="VAR_007961" FT VARIANT 160 FT /note="R -> C (in dbSNP:rs28362462)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_022201" FT VARIANT 162 FT /note="D -> N (in Le(-) individuals; about 20% of alpha FT (1,3/1,4)fucosyltransferase activity; dbSNP:rs28362463)" FT /evidence="ECO:0000269|PubMed:10211701, FT ECO:0000269|PubMed:9703429, ECO:0000269|Ref.6" FT /id="VAR_007962" FT VARIANT 170 FT /note="G -> S (in Le(-) individuals; completely inactive; FT dbSNP:rs3745635)" FT /evidence="ECO:0000269|PubMed:8219240, FT ECO:0000269|PubMed:8240337, ECO:0000269|Ref.6" FT /id="VAR_003428" FT VARIANT 223 FT /note="G -> R (in Le(-) individuals; Loss of alpha FT (1,3/1,4)fucosyltransferase activity.; dbSNP:rs28362466)" FT /evidence="ECO:0000269|PubMed:10211701, FT ECO:0000269|PubMed:9703429, ECO:0000269|Ref.6" FT /id="VAR_007963" FT VARIANT 270 FT /note="V -> M (in Le(-) individuals; Loss of alpha FT (1,3/1,4)fucosyltransferase activity.; dbSNP:rs28381968)" FT /evidence="ECO:0000269|PubMed:10211701, FT ECO:0000269|PubMed:9703429, ECO:0000269|Ref.6" FT /id="VAR_007964" FT VARIANT 325 FT /note="T -> M (in dbSNP:rs28381969)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_022202" FT VARIANT 327 FT /note="R -> Q (in dbSNP:rs28381970)" FT /evidence="ECO:0000269|Ref.6" FT /id="VAR_022203" FT VARIANT 336 FT /note="D -> A (in Le(-) individuals; dbSNP:rs151218854)" FT /evidence="ECO:0000269|PubMed:8240337" FT /id="VAR_003429" FT VARIANT 356 FT /note="I -> K (in Le(-) individuals; less than 10% FT reduction in activity; dbSNP:rs3894326)" FT /evidence="ECO:0000269|PubMed:7961897, FT ECO:0000269|PubMed:8063716, ECO:0000269|PubMed:8801770" FT /id="VAR_003430" SQ SEQUENCE 361 AA; 42117 MW; 5EC3A1E3DBA51842 CRC64; MDPLGAAKPQ WPWRRCLAAL LFQLLVAVCF FSYLRVSRDD ATGSPRAPSG SSRQDTTPTR PTLLILLRTW PFHIPVALSR CSEMVPGTAD CHITADRKVY PQADMVIVHH WDIMSNPKSR LPPSPRPQGQ RWIWFNLEPP PNCQHLEALD RYFNLTMSYR SDSDIFTPYG WLEPWSGQPA HPPLNLSAKT ELVAWAVSNW KPDSARVRYY QSLQAHLKVD VYGRSHKPLP KGTMMETLSR YKFYLAFENS LHPDYITEKL WRNALEAWAV PVVLGPSRSN YERFLPPDAF IHVDDFQSPK DLARYLQELD KDHARYLSYF RWRETLRPRS FSWALDFCKA CWKLQQESRY QTVRSIAAWF T //