FUT6_HUMAN
ID FUT6_HUMAN Reviewed; 359 AA.
AC P51993; A6NEX0; D6W637; Q9UND8;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase FUT6 {ECO:0000305};
DE EC=2.4.1.152 {ECO:0000269|PubMed:17604274, ECO:0000269|PubMed:9363434};
DE AltName: Full=Fucosyltransferase 6;
DE AltName: Full=Fucosyltransferase VI;
DE Short=Fuc-TVI;
DE Short=FucT-VI;
DE AltName: Full=Galactoside 3-L-fucosyltransferase;
GN Name=FUT6 {ECO:0000312|HGNC:HGNC:4017}; Synonyms=FCT3A;
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] (ISOFORM 1), FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=1520296; DOI=10.1016/s0006-291x(05)81472-x;
RA Koszdin K.L., Bowen B.R.;
RT "The cloning and expression of a human alpha-1,3 fucosyltransferase capable
RT of forming the E-selectin ligand.";
RL Biochem. Biophys. Res. Commun. 187:152-157(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), FUNCTION, AND CATALYTIC
RP ACTIVITY.
RX PubMed=1339443; DOI=10.1016/s0021-9258(18)35803-4;
RA Weston B.W., Smith P.L., Kelly R.J., Lowe J.B.;
RT "Molecular cloning of a fourth member of a human alpha
RT (1,3)fucosyltransferase gene family. Multiple homologous sequences that
RT determine expression of the Lewis x, sialyl Lewis x, and difucosyl sialyl
RT Lewis x epitopes.";
RL J. Biol. Chem. 267:24575-24584(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, AND CATALYTIC
RP ACTIVITY.
RC TISSUE=Kidney;
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] (ISOFORM 1), AND VARIANT SER-124.
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)-fucosyltransferase.";
RL Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP PARTIAL PROTEIN SEQUENCE, SUBCELLULAR LOCATION, GLYCOSYLATION, PROTEOLYTIC
RP CLEAVAGE, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=9451035; DOI=10.1093/glycob/8.3.259;
RA Borsig L., Katopodis A.G., Bowen B.R., Berger E.G.;
RT "Trafficking and localization studies of recombinant alpha1, 3-
RT fucosyltransferase VI stably expressed in CHO cells.";
RL Glycobiology 8:259-268(1998).
RN [8]
RP CATALYTIC ACTIVITY, AND FUNCTION.
RX PubMed=9363434; DOI=10.1093/glycob/7.7.921;
RA De Vries T., Palcic M.P., Schoenmakers P.S., Van Den Eijnden D.H.,
RA Joziasse D.H.;
RT "Acceptor specificity of GDP-Fuc:Gal beta 1-->4GlcNAc-R alpha 3-
RT fucosyltransferase VI (FucT VI) expressed in insect cells as soluble,
RT secreted enzyme.";
RL Glycobiology 7:921-927(1997).
RN [9]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=10728707;
RA Izawa M., Kumamoto K., Mitsuoka C., Kanamori C., Kanamori A., Ohmori K.,
RA Ishida H., Nakamura S., Kurata-Miura K., Sasaki K., Nishi T., Kannagi R.;
RT "Expression of sialyl 6-sulfo Lewis X is inversely correlated with
RT conventional sialyl Lewis X expression in human colorectal cancer.";
RL Cancer Res. 60:1410-1416(2000).
RN [10]
RP CATALYTIC ACTIVITY, FUNCTION, REGION, AND MUTAGENESIS OF LYS-73; ARG-110;
RP GLU-111 AND VAL-112.
RX PubMed=17604274; DOI=10.1074/jbc.m702395200;
RA Shetterly S., Jost F., Watson S.R., Knegtel R., Macher B.A., Holmes E.H.;
RT "Site-specific fucosylation of sialylated polylactosamines by alpha1,3/4-
RT fucosyltransferases-V and -VI Is defined by amino acids near the N terminus
RT of the catalytic domain.";
RL J. Biol. Chem. 282:24882-24892(2007).
RN [11]
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 [12]
RP POLYMORPHISM, VARIANT LYS-247, AND CHARACTERIZATION OF VARIANT LYS-247.
RX PubMed=8175676; DOI=10.1016/s0021-9258(18)99927-8;
RA Mollicone R., Reguigne I., Fletcher A., Aziz A., Rustam M., Weston B.W.,
RA Kelly R.J., Lowe J.B., Oriol R.;
RT "Molecular basis for plasma alpha(1,3)-fucosyltransferase gene deficiency
RT (FUT6).";
RL J. Biol. Chem. 269:12662-12671(1994).
RN [13]
RP VARIANTS SER-124; VAL-244; LYS-247 AND GLY-303, AND CHARACTERIZATION OF
RP VARIANTS SER-124; VAL-244; LYS-247 AND GLY-303.
RX PubMed=11102976;
RX DOI=10.1002/1098-1004(200012)16:6<473::aid-humu4>3.0.co;2-t;
RA Elmgren A., Borjeson C., Mollicone R., Oriol R., Fletcher A., Larson G.;
RT "Identification of two functionally deficient plasma alpha 3-
RT fucosyltransferase (FUT6) alleles.";
RL Hum. Mutat. 16:473-481(2000).
RN [14]
RP VARIANTS SER-124; LYS-247 AND GLY-303.
RX PubMed=27535533; DOI=10.1038/nature19057;
RG Exome Aggregation Consortium;
RA Lek M., Karczewski K.J., Minikel E.V., Samocha K.E., Banks E., Fennell T.,
RA O'Donnell-Luria A.H., Ware J.S., Hill A.J., Cummings B.B., Tukiainen T.,
RA Birnbaum D.P., Kosmicki J.A., Duncan L.E., Estrada K., Zhao F., Zou J.,
RA Pierce-Hoffman E., Berghout J., Cooper D.N., Deflaux N., DePristo M.,
RA Do R., Flannick J., Fromer M., Gauthier L., Goldstein J., Gupta N.,
RA Howrigan D., Kiezun A., Kurki M.I., Moonshine A.L., Natarajan P.,
RA Orozco L., Peloso G.M., Poplin R., Rivas M.A., Ruano-Rubio V., Rose S.A.,
RA Ruderfer D.M., Shakir K., Stenson P.D., Stevens C., Thomas B.P., Tiao G.,
RA Tusie-Luna M.T., Weisburd B., Won H.H., Yu D., Altshuler D.M.,
RA Ardissino D., Boehnke M., Danesh J., Donnelly S., Elosua R., Florez J.C.,
RA Gabriel S.B., Getz G., Glatt S.J., Hultman C.M., Kathiresan S., Laakso M.,
RA McCarroll S., McCarthy M.I., McGovern D., McPherson R., Neale B.M.,
RA Palotie A., Purcell S.M., Saleheen D., Scharf J.M., Sklar P.,
RA Sullivan P.F., Tuomilehto J., Tsuang M.T., Watkins H.C., Wilson J.G.,
RA Daly M.J., MacArthur D.G.;
RT "Analysis of protein-coding genetic variation in 60,706 humans.";
RL Nature 536:285-291(2016).
CC -!- FUNCTION: [Isoform 1]: Catalyzes the transfer of L-fucose, from a
CC guanosine diphosphate-beta-L-fucose, to the N-acetyl glucosamine
CC (GlcNAc) of a distal alpha2,3 sialylated lactosamine unit of a
CC glycoprotein- or a glycolipid-linked sialopolylactosamines chain or of
CC a distal or internal lactosamine unit of a neutral glycoprotein- or a
CC glycolipid-linked polylactosamines chain through an alpha-1,3
CC glycosidic linkage and participates in surface expression of the sialyl
CC Lewis X (sLe(x)), Lewis X (Le(x)) and non sialylated VIM2 determinants
CC (PubMed:9451035, PubMed:1520296, PubMed:1339443, PubMed:7650030,
CC PubMed:17604274, PubMed:9363434, PubMed:10728707, PubMed:29593094).
CC Moreover transfers fucose to H-type 2 (Fucalpha1-2Galbeta1-4GlcNAc)
CC chain acceptor substrates and participates in difucosylated sialyl
CC Lewis x determinants (PubMed:17604274, PubMed:1339443). Also
CC fucosylates a polylactosamine substrate having a 6 sulfate modification
CC at the GlcNAc moiety and gives rise to sialyl and non-sialyl 6-sulfo
CC lewis X (PubMed:10728707). Does not have activity towards type 1
CC ((Galbeta1-3GlcNAc)) and H-type 1 chain (Fucalpha1-2Galbeta1-3GlcNAc)
CC acceptors substrates (PubMed:1339443, PubMed:17604274, PubMed:9363434).
CC {ECO:0000269|PubMed:10728707, ECO:0000269|PubMed:1339443,
CC ECO:0000269|PubMed:1520296, ECO:0000269|PubMed:17604274,
CC ECO:0000269|PubMed:7650030, ECO:0000269|PubMed:9363434,
CC ECO:0000269|PubMed:9451035}.
CC -!- FUNCTION: [Isoform 2]: Does not have alpha(1,3)-fucosyltransferase
CC activity. {ECO:0000269|PubMed:7650030}.
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:17604274,
CC ECO:0000269|PubMed:29593094, ECO:0000269|PubMed:9363434};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14258;
CC Evidence={ECO:0000305|PubMed:17604274, ECO:0000305|PubMed:29593094};
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=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=beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl-(1->3)-
CC beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl-(1->3)-beta-D-
CC galactosyl-(1->4)-beta-D-glucosyl-(1<->1')-ceramide + GDP-beta-L-
CC fucose = beta-D-galactosyl-(1->4)-[alpha-L-fucosyl-(1->3)]-N-acetyl-
CC beta-D-glucosaminyl-(1->3)-beta-D-galactosyl-(1->4)-N-acetyl-beta-D-
CC glucosaminyl-(1->3)-beta-D-galactosyl-(1->4)-beta-D-glucosyl-
CC (1<->1')-ceramide + GDP + H(+); Xref=Rhea:RHEA:48368,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57273, ChEBI:CHEBI:58189,
CC ChEBI:CHEBI:90357, ChEBI:CHEBI:90360;
CC Evidence={ECO:0000269|PubMed:17604274};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48369;
CC Evidence={ECO:0000305|PubMed:17604274};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl-(1->3)-
CC beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl-(1->3)-beta-D-
CC galactosyl-(1->4)-beta-D-glucosyl-(1<->1')-ceramide + GDP-beta-L-
CC fucose = beta-D-galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl-
CC (1->3)-beta-D-galactosyl-(1->4)-[alpha-L-fucosyl-(1->3)]-N-acetyl-
CC beta-D-glucosaminyl-(1->3)-beta-D-galactosyl-(1->4)-beta-D-glucosyl-
CC (1<->1')-ceramide + GDP + H(+); Xref=Rhea:RHEA:48364,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57273, ChEBI:CHEBI:58189,
CC ChEBI:CHEBI:90357, ChEBI:CHEBI:90358;
CC Evidence={ECO:0000269|PubMed:17604274};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48365;
CC Evidence={ECO:0000305|PubMed:17604274};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GDP-beta-L-fucose + N-acetyl-alpha-neuraminosyl-(2->3)-beta-D-
CC galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl-(1->3)-beta-D-
CC galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl-(1->3)-beta-D-
CC galactosyl-(1->4)-beta-D-glucosyl-(1<->1')-ceramide = GDP + H(+) + N-
CC acetyl-alpha-neuraminosyl-(2->3)-beta-D-galactosyl-(1->4)-[alpha-L-
CC fucosyl-(1->3)]-N-acetyl-beta-D-glucosaminyl-(1->3)-beta-D-
CC galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl-(1->3)-beta-D-
CC galactosyl-(1->4)-beta-D-glucosyl-(1<->1')-ceramide;
CC Xref=Rhea:RHEA:48356, ChEBI:CHEBI:15378, ChEBI:CHEBI:57273,
CC ChEBI:CHEBI:58189, ChEBI:CHEBI:90336, ChEBI:CHEBI:90339;
CC Evidence={ECO:0000269|PubMed:17604274};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:48357;
CC Evidence={ECO:0000305|PubMed:17604274};
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:10728707,
CC ECO:0000269|PubMed:1339443, ECO:0000269|PubMed:1520296,
CC ECO:0000269|PubMed:7650030, ECO:0000269|PubMed:9363434,
CC ECO:0000269|PubMed:9451035};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62825;
CC Evidence={ECO:0000269|PubMed:1339443};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=GDP-beta-L-fucose + N-acetyl-alpha-neuraminosyl-(2->3)-beta-D-
CC galactosyl-(1->4)-N-acetyl-beta-D-glucosamine = GDP + H(+) + N-
CC acetyl-alpha-neuraminosyl-(2->3)-beta-D-galactosyl-(1->4)-[alpha-L-
CC fucosyl-(1->3)]-N-acetyl-beta-D-glucosamine; Xref=Rhea:RHEA:62836,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57273, ChEBI:CHEBI:58189,
CC ChEBI:CHEBI:145937, ChEBI:CHEBI:145938;
CC Evidence={ECO:0000269|PubMed:10728707, ECO:0000269|PubMed:1339443,
CC ECO:0000269|PubMed:1520296, ECO:0000269|PubMed:7650030,
CC ECO:0000269|PubMed:9363434, ECO:0000269|PubMed:9451035};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62837;
CC Evidence={ECO:0000305|PubMed:1520296};
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:1520296};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62889;
CC Evidence={ECO:0000305|PubMed:1520296};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=alpha-L-Fuc-(1->2)-beta-D-Gal-(1->4)-D-Glc + GDP-beta-L-fucose
CC = alpha-L-Fuc-(1->2)-beta-D-Gal-(1->4)-[alpha-L-Fuc-(1->3)]-D-Glc +
CC GDP + H(+); Xref=Rhea:RHEA:64016, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57273, ChEBI:CHEBI:58189, ChEBI:CHEBI:147155,
CC ChEBI:CHEBI:149659; Evidence={ECO:0000269|PubMed:1520296};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64017;
CC Evidence={ECO:0000305|PubMed:1520296};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a beta-D-galactosyl-(1->4)-N-acetyl-beta-D-6-sulfooxy-
CC glucosaminyl derivative + GDP-beta-L-fucose = a beta-D-galactosyl-
CC (1->4)-[alpha-L-fucosyl-(1->3)]-N-acetyl-beta-D-6-sulfooxy-
CC glucosaminyl derivative + GDP + H(+); Xref=Rhea:RHEA:64032,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57273, ChEBI:CHEBI:58189,
CC ChEBI:CHEBI:149663, ChEBI:CHEBI:149664;
CC Evidence={ECO:0000269|PubMed:10728707};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000269|PubMed:29593094, ECO:0000269|PubMed:9363434}.
CC -!- SUBUNIT: Homodimer and monomer (PubMed:9451035). Monomer (secreted
CC form) (PubMed:9451035). {ECO:0000269|PubMed:9451035}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane; Single-
CC pass type II membrane protein. Golgi apparatus
CC {ECO:0000269|PubMed:9451035}. Secreted {ECO:0000269|PubMed:9451035}.
CC Note=Membrane-bound form in trans cisternae of Golgi.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P51993-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P51993-2; Sequence=VSP_001780;
CC -!- TISSUE SPECIFICITY: Kidney, liver, colon, small intestine, bladder,
CC uterus and salivary gland.
CC -!- PTM: N-glycosylated. {ECO:0000269|PubMed:9451035}.
CC -!- PTM: Proteolytic cleavage releases a secreted glycoform of 43 kDa.
CC {ECO:0000269|PubMed:9451035}.
CC -!- POLYMORPHISM: Expression of alpha(1,3)-fucosyltransferase in plasma can
CC vary among different populations. 9% of individuals on the isle of Java
CC (Indonesia) do not express this enzyme. Ninety-five percent of plasma
CC alpha(1,3)-fucosyltransferase-deficient individuals have Lewis negative
CC phenotype on red cells, suggesting strong linkage disequilibrium
CC between these two traits. Variations in FUT6 are responsible for plasma
CC alpha(1,3)-fucosyltransferase deficiency [MIM:613852].
CC -!- SIMILARITY: Belongs to the glycosyltransferase 10 family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAC50191.1; Type=Miscellaneous discrepancy; Note=Probable cloning artifact.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - GTase;
CC Note=Fucosyltransferase 6;
CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_603";
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DR EMBL; M98825; AAA99222.1; -; mRNA.
DR EMBL; L01698; AAB03078.1; -; Genomic_DNA.
DR EMBL; U27331; AAC50190.1; -; mRNA.
DR EMBL; U27332; AAC50191.1; ALT_SEQ; mRNA.
DR EMBL; U27333; AAC50192.1; -; mRNA.
DR EMBL; U27334; AAC50193.1; -; mRNA.
DR EMBL; U27335; AAC50194.1; -; mRNA.
DR EMBL; U27336; AAC50195.1; -; mRNA.
DR EMBL; U27337; AAC50196.1; -; mRNA.
DR EMBL; AF131211; AAD33509.1; -; mRNA.
DR EMBL; AL031258; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471139; EAW69136.1; -; Genomic_DNA.
DR EMBL; CH471139; EAW69137.1; -; Genomic_DNA.
DR EMBL; CH471139; EAW69138.1; -; Genomic_DNA.
DR EMBL; CH471139; EAW69139.1; -; Genomic_DNA.
DR CCDS; CCDS12152.1; -. [P51993-1]
DR PIR; A45156; A45156.
DR PIR; I39048; I39048.
DR PIR; I39049; I39049.
DR RefSeq; NP_000141.1; NM_000150.2. [P51993-1]
DR RefSeq; NP_001035791.1; NM_001040701.1. [P51993-1]
DR RefSeq; XP_005259583.1; XM_005259526.4.
DR RefSeq; XP_011526170.1; XM_011527868.2.
DR RefSeq; XP_011526171.1; XM_011527869.2.
DR RefSeq; XP_011526172.1; XM_011527870.2.
DR RefSeq; XP_011526174.1; XM_011527872.2. [P51993-1]
DR RefSeq; XP_011526175.1; XM_011527873.2.
DR RefSeq; XP_011526176.1; XM_011527874.2.
DR RefSeq; XP_011526177.1; XM_011527875.2. [P51993-1]
DR RefSeq; XP_011526178.1; XM_011527876.2.
DR RefSeq; XP_011526180.1; XM_011527878.2.
DR RefSeq; XP_011526181.1; XM_011527879.2.
DR AlphaFoldDB; P51993; -.
DR STRING; 9606.ENSP00000313398; -.
DR BindingDB; P51993; -.
DR ChEMBL; CHEMBL4443; -.
DR SwissLipids; SLP:000001436; -. [P51993-1]
DR CAZy; GT10; Glycosyltransferase Family 10.
DR GlyGen; P51993; 4 sites.
DR iPTMnet; P51993; -.
DR PhosphoSitePlus; P51993; -.
DR BioMuta; FUT6; -.
DR DMDM; 1730136; -.
DR EPD; P51993; -.
DR jPOST; P51993; -.
DR MassIVE; P51993; -.
DR MaxQB; P51993; -.
DR PaxDb; P51993; -.
DR PeptideAtlas; P51993; -.
DR PRIDE; P51993; -.
DR ProteomicsDB; 56467; -. [P51993-1]
DR ProteomicsDB; 56468; -. [P51993-2]
DR Antibodypedia; 24005; 252 antibodies from 27 providers.
DR DNASU; 2528; -.
DR Ensembl; ENST00000286955.5; ENSP00000286955.5; ENSG00000156413.15. [P51993-1]
DR Ensembl; ENST00000318336.10; ENSP00000313398.4; ENSG00000156413.15. [P51993-1]
DR Ensembl; ENST00000524754.1; ENSP00000431708.1; ENSG00000156413.15. [P51993-1]
DR Ensembl; ENST00000527106.5; ENSP00000432954.1; ENSG00000156413.15. [P51993-1]
DR Ensembl; ENST00000592563.1; ENSP00000466016.1; ENSG00000156413.15. [P51993-2]
DR GeneID; 2528; -.
DR KEGG; hsa:2528; -.
DR MANE-Select; ENST00000318336.10; ENSP00000313398.4; NM_000150.4; NP_000141.1.
DR UCSC; uc002mdf.2; human. [P51993-1]
DR CTD; 2528; -.
DR DisGeNET; 2528; -.
DR GeneCards; FUT6; -.
DR HGNC; HGNC:4017; FUT6.
DR HPA; ENSG00000156413; Tissue enhanced (esophagus, kidney, salivary gland).
DR MalaCards; FUT6; -.
DR MIM; 136836; gene.
DR MIM; 613852; phenotype.
DR neXtProt; NX_P51993; -.
DR OpenTargets; ENSG00000156413; -.
DR PharmGKB; PA28433; -.
DR VEuPathDB; HostDB:ENSG00000156413; -.
DR eggNOG; KOG2619; Eukaryota.
DR GeneTree; ENSGT00940000163389; -.
DR HOGENOM; CLU_032075_4_1_1; -.
DR InParanoid; P51993; -.
DR OMA; RFTFSNC; -.
DR PhylomeDB; P51993; -.
DR TreeFam; TF316348; -.
DR BioCyc; MetaCyc:HS08124-MON; -.
DR BRENDA; 2.4.1.152; 2681.
DR BRENDA; 2.4.1.65; 2681.
DR PathwayCommons; P51993; -.
DR Reactome; R-HSA-9037629; Lewis blood group biosynthesis.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 2528; 19 hits in 1053 CRISPR screens.
DR ChiTaRS; FUT6; human.
DR GeneWiki; FUT6; -.
DR GenomeRNAi; 2528; -.
DR Pharos; P51993; Tchem.
DR PRO; PR:P51993; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P51993; protein.
DR Bgee; ENSG00000156413; Expressed in lower esophagus mucosa and 152 other tissues.
DR ExpressionAtlas; P51993; baseline and differential.
DR Genevisible; P51993; HS.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA: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:0017083; F:4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0046920; F:alpha-(1->3)-fucosyltransferase activity; IBA:GO_Central.
DR GO; GO:0008417; F:fucosyltransferase activity; IDA:BHF-UCL.
DR GO; GO:0006672; P:ceramide metabolic process; IDA:BHF-UCL.
DR GO; GO:0036065; P:fucosylation; IBA:GO_Central.
DR GO; GO:0006688; P:glycosphingolipid biosynthetic process; IDA:UniProtKB.
DR GO; GO:0042355; P:L-fucose catabolic process; NAS:UniProtKB.
DR GO; GO:0036071; P:N-glycan fucosylation; IDA:UniProtKB.
DR GO; GO:0009312; P:oligosaccharide biosynthetic process; TAS:Reactome.
DR GO; GO:0006486; P:protein glycosylation; TAS:UniProtKB.
DR GO; GO:0006487; P:protein N-linked glycosylation; IDA:UniProtKB.
DR GO; GO:0006493; P:protein O-linked glycosylation; IDA: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 Alternative splicing; Direct protein sequencing; Glycoprotein;
KW Glycosyltransferase; Golgi apparatus; Lipid metabolism; Membrane;
KW Reference proteome; Secreted; Signal-anchor; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..359
FT /note="4-galactosyl-N-acetylglucosaminide 3-alpha-L-
FT fucosyltransferase FUT6"
FT /id="PRO_0000221110"
FT TOPO_DOM 1..14
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 15..34
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 35..359
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 73..112
FT /note="determines site-specific fucosylation"
FT /evidence="ECO:0000269|PubMed:17604274"
FT CARBOHYD 46
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 91
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 153
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 184
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 348..359
FT /note="RYQTRGIAAWFT -> SGGLIYLRTRLPEASPA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:7650030"
FT /id="VSP_001780"
FT VARIANT 124
FT /note="P -> S (found in individuals with plasma alpha(1,3)-
FT fucosyltransferase deficiency and no clinically relevant
FT phenotype; results in partial enzyme inactivation; complete
FT enzyme inactivation when associated with V-244 and G-303;
FT dbSNP:rs778805)"
FT /evidence="ECO:0000269|PubMed:11102976,
FT ECO:0000269|PubMed:27535533, ECO:0000269|Ref.4"
FT /id="VAR_024463"
FT VARIANT 230
FT /note="Q -> K (in dbSNP:rs364637)"
FT /id="VAR_024464"
FT VARIANT 244
FT /note="L -> V (found in individuals with plasma alpha(1,3)-
FT fucosyltransferase deficiency and no clinically relevant
FT phenotype; complete enzyme inactivation when associated
FT with S-124 and G-303)"
FT /evidence="ECO:0000269|PubMed:11102976"
FT /id="VAR_065915"
FT VARIANT 247
FT /note="E -> K (found in individuals with plasma alpha(1,3)-
FT fucosyltransferase deficiency and no clinically relevant
FT phenotype; complete enzyme inactivation; dbSNP:rs17855739)"
FT /evidence="ECO:0000269|PubMed:11102976,
FT ECO:0000269|PubMed:27535533, ECO:0000269|PubMed:8175676"
FT /id="VAR_065916"
FT VARIANT 303
FT /note="R -> G (found in individuals with plasma alpha(1,3)-
FT fucosyltransferase deficiency and no clinically relevant
FT phenotype; complete enzyme inactivation when associated
FT with S-124 and V-244; dbSNP:rs61147939)"
FT /evidence="ECO:0000269|PubMed:11102976,
FT ECO:0000269|PubMed:27535533"
FT /id="VAR_065917"
FT MUTAGEN 73
FT /note="K->T: Loss of site-specific fucosylation leading to
FT generation of approximately equal amounts of VIM2 and
FT sialyl-lewis x. Reverse the site-specific fucosylation
FT pattern leading to generation of VIM2 predominantly instead
FT of sialyl-lewis x; when associated with W-110; D-111 and I-
FT 112. Increases VIM2 glycolipid product; when associated
FT with W-110; D-111 and I-112."
FT /evidence="ECO:0000269|PubMed:17604274"
FT MUTAGEN 110
FT /note="R->W: Reduces dramatically
FT alpha(1,3)fucosyltransferase activity towards type 2 chain
FT acceptors. Loss of site-specific fucosylation leading to
FT generation of approximately equal amounts of VIM2 and
FT sialyl-lewis x. Reverse the site-specific fucosylation
FT pattern leading to generation of VIM2 predominantly instead
FT of sialyl-lewis x; when associated with T-73; D-111 and I-
FT 112. Increases VIM2 glycolipid product; when associated
FT with T-73; D-111 and I-112."
FT /evidence="ECO:0000269|PubMed:17604274"
FT MUTAGEN 111
FT /note="E->D: Reverse the site-specific fucosylation pattern
FT leading to generation of VIM2 predominantly instead of
FT sialyl-lewis x; when associated with T-73; W-110 and I-112.
FT Increases VIM2 glycolipid product; when associated with T-
FT 73; W-110 and I-112."
FT /evidence="ECO:0000269|PubMed:17604274"
FT MUTAGEN 112
FT /note="V->I: Reverse the site-specific fucosylation pattern
FT leading to generation of VIM2 predominantly instead of
FT sialyl-lewis x; when associated with T-73; W-110 and D-111.
FT Increases VIM2 glycolipid product; when associated with T-
FT 73; W-110 and D-111."
FT /evidence="ECO:0000269|PubMed:17604274"
SQ SEQUENCE 359 AA; 41860 MW; 67ABDF058F0999DA CRC64;
MDPLGPAKPQ WSWRCCLTTL LFQLLMAVCF FSYLRVSQDD PTVYPNGSRF PDSTGTPAHS
IPLILLWTWP FNKPIALPRC SEMVPGTADC NITADRKVYP QADAVIVHHR EVMYNPSAQL
PRSPRRQGQR WIWFSMESPS HCWQLKAMDG YFNLTMSYRS DSDIFTPYGW LEPWSGQPAH
PPLNLSAKTE LVAWAVSNWG PNSARVRYYQ SLQAHLKVDV YGRSHKPLPQ GTMMETLSRY
KFYLAFENSL HPDYITEKLW RNALEAWAVP VVLGPSRSNY ERFLPPDAFI HVDDFQSPKD
LARYLQELDK DHARYLSYFR WRETLRPRSF SWALAFCKAC WKLQEESRYQ TRGIAAWFT
