FUT3_HUMAN
ID FUT3_HUMAN Reviewed; 361 AA.
AC P21217; B5U7U9; B5U7V0; Q32NE7; Q99448; Q99449;
DT 01-MAY-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1991, sequence version 1.
DT 03-AUG-2022, entry version 205.
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], CATALYTIC 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 [MRNA].
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LE(-) ARG-68 AND MET-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 [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LE(-) ARG-20; ARG-68; MET-105;
RP ASN-162; SER-170; ARG-223 AND MET-270, AND VARIANTS SER-5; CYS-160; MET-325
RP AND GLN-327.
RG SeattleSNPs variation discovery resource;
RL Submitted (DEC-2004) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANTS LE(-) ARG-68
RP AND MET-105.
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [8]
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 [9]
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 [10]
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 [11]
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 [12]
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 [13]
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 [14]
RP VARIANTS LE(-) ARG-20; SER-170 AND ALA-336.
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 [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 and participates in the blood groups Lewis
CC determination and expression of Lewis a (Le(a)), lewis b (Le(b)), Lewis
CC x/SSEA-1 (Le(x)) and lewis y (Le(y)) antigens (PubMed:12668675,
CC PubMed:1977660, PubMed:11058871). Also catalyzes the transfer of L-
CC fucose to subterminal GlcNAc of sialyl- and disialyl-
CC lactotetraosylceramide to produce sialyl Lewis a (sLe(a)) and disialyl
CC Lewis a via an alpha(1,4) linkage and therefore may regulate cell
CC surface sialyl Lewis 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 = GDP + H(+) +
CC III(4)-a-Fuc-Lc4Cer(d18:1(4E)); 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=0.10 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.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:7721776}.
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";
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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 BioGRID; 108801; 96.
DR IntAct; P21217; 21.
DR STRING; 9606.ENSP00000305603; -.
DR ChEMBL; CHEMBL3269; -.
DR SwissLipids; SLP:000001370; -.
DR CAZy; GT10; Glycosyltransferase Family 10.
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; P21217; -.
DR PeptideAtlas; P21217; -.
DR PRIDE; P21217; -.
DR ProteomicsDB; 53853; -.
DR Antibodypedia; 11767; 524 antibodies from 35 providers.
DR DNASU; 2525; -.
DR Ensembl; ENST00000303225.11; 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 GeneID; 2525; -.
DR KEGG; hsa:2525; -.
DR UCSC; uc002mdj.3; human.
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+phenotype.
DR neXtProt; NX_P21217; -.
DR PharmGKB; PA28430; -.
DR VEuPathDB; HostDB:ENSG00000171124; -.
DR eggNOG; KOG2619; Eukaryota.
DR HOGENOM; CLU_032075_4_1_1; -.
DR InParanoid; P21217; -.
DR OrthoDB; 551308at2759; -.
DR PhylomeDB; P21217; -.
DR TreeFam; TF316348; -.
DR BioCyc; MetaCyc:HS10249-MON; -.
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; 4 hits in 1059 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 147 other tissues.
DR ExpressionAtlas; P21217; baseline and differential.
DR Genevisible; P21217; HS.
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:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
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; -; 1.
DR InterPro; IPR031481; Glyco_tran_10_N.
DR InterPro; IPR001503; Glyco_trans_10.
DR InterPro; IPR038577; GT10-like_C_sf.
DR PANTHER; PTHR11929; PTHR11929; 1.
DR Pfam; PF17039; Glyco_tran_10_N; 1.
DR Pfam; PF00852; Glyco_transf_10; 1.
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.5"
FT /id="VAR_022200"
FT VARIANT 20
FT /note="L -> R (in Le(-); 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.5"
FT /id="VAR_003426"
FT VARIANT 68
FT /note="W -> R (in Le(-); dbSNP:rs812936)"
FT /evidence="ECO:0000269|PubMed:15057824,
FT ECO:0000269|PubMed:8801770, ECO:0000269|PubMed:9268337,
FT ECO:0000269|Ref.4, ECO:0000269|Ref.5"
FT /id="VAR_007959"
FT VARIANT 102
FT /note="Q -> K (in Le(+); dbSNP:rs59796499)"
FT /evidence="ECO:0000269|PubMed:9703429"
FT /id="VAR_007960"
FT VARIANT 105
FT /note="T -> M (in Le(-); dbSNP:rs778986)"
FT /evidence="ECO:0000269|PubMed:15057824,
FT ECO:0000269|PubMed:8240322, ECO:0000269|PubMed:8801770,
FT ECO:0000269|PubMed:9268337, ECO:0000269|Ref.4,
FT ECO:0000269|Ref.5"
FT /id="VAR_003427"
FT VARIANT 124
FT /note="S -> A (in Le(+); 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.5"
FT /id="VAR_022201"
FT VARIANT 162
FT /note="D -> N (in Le(-); about 20% of alpha (1,3/
FT 1,4)fucosyltransferase activity; dbSNP:rs28362463)"
FT /evidence="ECO:0000269|PubMed:10211701,
FT ECO:0000269|PubMed:9703429, ECO:0000269|Ref.5"
FT /id="VAR_007962"
FT VARIANT 170
FT /note="G -> S (in Le(-); completely inactive;
FT dbSNP:rs3745635)"
FT /evidence="ECO:0000269|PubMed:8219240,
FT ECO:0000269|PubMed:8240337, ECO:0000269|Ref.5"
FT /id="VAR_003428"
FT VARIANT 223
FT /note="G -> R (in Le(-); Loss of alpha (1,3/
FT 1,4)fucosyltransferase activity.; dbSNP:rs28362466)"
FT /evidence="ECO:0000269|PubMed:10211701,
FT ECO:0000269|PubMed:9703429, ECO:0000269|Ref.5"
FT /id="VAR_007963"
FT VARIANT 270
FT /note="V -> M (in Le(-); Loss of alpha (1,3/
FT 1,4)fucosyltransferase activity.; dbSNP:rs28381968)"
FT /evidence="ECO:0000269|PubMed:10211701,
FT ECO:0000269|PubMed:9703429, ECO:0000269|Ref.5"
FT /id="VAR_007964"
FT VARIANT 325
FT /note="T -> M (in dbSNP:rs28381969)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_022202"
FT VARIANT 327
FT /note="R -> Q (in dbSNP:rs28381970)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_022203"
FT VARIANT 336
FT /note="D -> A (in Le(-); dbSNP:rs151218854)"
FT /evidence="ECO:0000269|PubMed:8240337"
FT /id="VAR_003429"
FT VARIANT 356
FT /note="I -> K (in Le(-); less than 10% reduction in
FT 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; BF4398044F19C284 CRC64;
MDPLGAAKPQ WPWRRCLAAL LFQLLVAVCF FSYLRVSRDD ATGSPRAPSG SSRQDTTPTR
PTLLILLWTW PFHIPVALSR CSEMVPGTAD CHITADRKVY PQADTVIVHH 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