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 02-SEP-2026, entry version 204. 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:10728707, PubMed:1339443, PubMed:1520296, PubMed:17604274, CC PubMed:29593094, PubMed:7650030, PubMed:9363434, PubMed:9451035). 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:1339443, PubMed:17604274). 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=a neolactoside nLc6Cer + GDP-beta-L-fucose = beta-D-Gal- CC (1->4)-[alpha-L-Fuc-(1->3)]-beta-D-GlcNAc-(1->3)-beta-D-Gal-(1->4)- CC beta-D-GlcNAc-(1->3)-beta-D-Gal-(1->4)-beta-D-Glc-(1<->1')-Cer + GDP CC + H(+); Xref=Rhea:RHEA:48368, ChEBI:CHEBI:15378, ChEBI:CHEBI:57273, CC ChEBI:CHEBI:58189, 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=a neolactoside nLc6Cer + GDP-beta-L-fucose = beta-D- CC galactosyl-(1->4)-N-acetyl-beta-D-glucosaminyl-(1->3)-beta-D- CC galactosyl-(1->4)-[alpha-L-fucosyl-(1->3)]-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: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=a neolactoside VI(3)-alpha-NeuNAc-nLc6Cer + GDP-beta-L-fucose CC = a neolactoside VI(3)-alpha-NeuAc,V(3)-alphaFuc-nLc6Cer + GDP + CC H(+); 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=N-acetyl-alpha-neuraminosyl-(2->3)-beta-D-galactosyl-(1->4)-N- CC acetyl-beta-D-glucosamine + GDP-beta-L-fucose = N-acetyl-alpha- CC neuraminosyl-(2->3)-beta-D-galactosyl-(1->4)-[alpha-L-fucosyl- CC (1->3)]-N-acetyl-beta-D-glucosamine + GDP + H(+); CC Xref=Rhea:RHEA:62836, ChEBI:CHEBI:15378, ChEBI:CHEBI:57273, CC ChEBI:CHEBI:58189, 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=lactose + GDP-beta-L-fucose = 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"; 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; 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_000150.4. [P51993-1] DR RefSeq; NP_001035791.1; NM_001040701.2. [P51993-1] DR RefSeq; NP_001356431.1; NM_001369502.1. [P51993-1] DR RefSeq; NP_001356433.1; NM_001369504.1. [P51993-1] DR RefSeq; NP_001356434.1; NM_001369505.1. [P51993-1] DR RefSeq; NP_001368884.1; NM_001381955.1. [P51993-1] DR RefSeq; NP_001368885.1; NM_001381956.1. [P51993-1] DR RefSeq; XP_047294509.1; XM_047438553.1. [P51993-1] DR RefSeq; XP_047294510.1; XM_047438554.1. [P51993-1] DR RefSeq; XP_047294511.1; XM_047438555.1. [P51993-1] DR RefSeq; XP_047294512.1; XM_047438556.1. [P51993-1] DR RefSeq; XP_047294513.1; XM_047438557.1. [P51993-1] DR RefSeq; XP_047294514.1; XM_047438558.1. [P51993-1] DR RefSeq; XP_047294515.1; XM_047438559.1. [P51993-1] DR RefSeq; XP_054176405.1; XM_054320430.1. [P51993-1] DR RefSeq; XP_054176406.1; XM_054320431.1. [P51993-1] DR RefSeq; XP_054176407.1; XM_054320432.1. [P51993-1] DR RefSeq; XP_054176408.1; XM_054320433.1. [P51993-1] DR RefSeq; XP_054176409.1; XM_054320434.1. [P51993-1] DR RefSeq; XP_054176410.1; XM_054320435.1. [P51993-1] DR RefSeq; XP_054176411.1; XM_054320436.1. [P51993-1] DR RefSeq; XP_054176412.1; XM_054320437.1. [P51993-1] DR RefSeq; XP_054176413.1; XM_054320438.1. [P51993-1] DR RefSeq; XP_054176414.1; XM_054320439.1. [P51993-1] DR RefSeq; XP_054176415.1; XM_054320440.1. [P51993-1] DR RefSeq; XP_054189233.1; XM_054333258.1. [P51993-1] DR RefSeq; XP_054189234.1; XM_054333259.1. [P51993-1] DR AlphaFoldDB; P51993; -. DR SMR; P51993; -. DR FunCoup; P51993; 125. DR STRING; 9606.ENSP00000286955; -. DR BindingDB; P51993; -. DR ChEMBL; CHEMBL4443; -. DR SwissLipids; SLP:000001436; -. [P51993-1] DR CAZy; GT10; Glycosyltransferase Family 10. DR GlyCosmos; P51993; 4 sites, No reported glycans. DR GlyGen; P51993; 5 sites, 8 N-linked glycans (1 site). DR iPTMnet; P51993; -. DR PhosphoSitePlus; P51993; -. DR BioMuta; FUT6; -. DR DMDM; 1730136; -. DR jPOST; P51993; -. DR MassIVE; P51993; -. DR PaxDb; 9606-ENSP00000286955; -. DR PeptideAtlas; P51993; -. DR PRIDE; P51993; -. DR ProteomicsDB; 56467; -. [P51993-1] DR ProteomicsDB; 56468; -. [P51993-2] DR Pumba; P51993; -. DR Antibodypedia; 24005; 250 antibodies from 29 providers. DR DNASU; 2528; -. DR Ensembl; ENST00000286955.5; ENSP00000286955.5; ENSG00000156413.16. [P51993-1] DR Ensembl; ENST00000318336.10; ENSP00000313398.4; ENSG00000156413.16. [P51993-1] DR Ensembl; ENST00000524754.1; ENSP00000431708.1; ENSG00000156413.16. [P51993-1] DR Ensembl; ENST00000527106.5; ENSP00000432954.1; ENSG00000156413.16. [P51993-1] DR Ensembl; ENST00000592563.1; ENSP00000466016.1; ENSG00000156413.16. [P51993-2] DR Ensembl; ENST00000905019.1; ENSP00000575078.1; ENSG00000156413.16. [P51993-1] DR Ensembl; ENST00000905020.1; ENSP00000575079.1; ENSG00000156413.16. [P51993-1] DR Ensembl; ENST00000905021.1; ENSP00000575080.1; ENSG00000156413.16. [P51993-1] DR Ensembl; ENST00000962499.1; ENSP00000632558.1; ENSG00000156413.16. [P51993-1] 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 AGR; HGNC:4017; -. DR ClinPGx; PA28433; -. 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 OpenTargets; ENSG00000156413; -. DR VEuPathDB; HostDB:ENSG00000156413; -. DR eggNOG; KOG2619; Eukaryota. DR GeneTree; ENSGT00940000163389; -. DR HOGENOM; CLU_032075_4_1_1; -. DR InParanoid; P51993; -. DR OMA; CKACRIL; -. DR OrthoDB; 427096at2759; -. DR PAN-GO; P51993; 3 GO annotations based on evolutionary models. DR PhylomeDB; P51993; -. DR BioCyc; MetaCyc:HS08124-MONOMER; -. 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 Agora; ENSG00000156413; -. DR BioGRID-ORCS; 2528; 22 hits in 1131 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 153 other cell types or tissues. DR ExpressionAtlas; P51993; baseline and differential. 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:0017083; F:4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase activity; IDA:UniProtKB. DR GO; GO:0046920; F:alpha-(1->3)-fucosyltransferase activity; TAS:UniProtKB. DR GO; GO:0008417; F:fucosyltransferase activity; IDA:BHF-UCL. DR GO; GO:0006672; P:ceramide metabolic process; IDA:BHF-UCL. DR GO; GO:0009101; P:glycoprotein biosynthetic process; TAS:UniProtKB. DR GO; GO:0006688; P:glycosphingolipid biosynthetic process; IDA:UniProtKB. DR GO; GO:0042355; P:L-fucose catabolic process; NAS:UniProtKB. DR GO; GO:0009312; P:oligosaccharide biosynthetic process; TAS:Reactome. 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:0036066; P:protein O-linked glycosylation via fucose; IDA:UniProtKB. DR FunFam; 3.40.50.11660:FF:000001; alpha-(1,3)-fucosyltransferase 9; 1. DR Gene3D; 3.40.50.11660; Glycosyl transferase family 10, C-terminal domain; 1. DR InterPro; IPR055270; Glyco_tran_10_C. DR InterPro; IPR031481; Glyco_tran_10_N. DR InterPro; IPR001503; Glyco_trans_10. DR InterPro; IPR038577; GT10-like_C_sf. DR PANTHER; PTHR11929:SF227; 4-GALACTOSYL-N-ACETYLGLUCOSAMINIDE 3-ALPHA-L-FUCOSYLTRANSFERASE FUT6; 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. PE 1: Evidence at protein level; KW Alternative splicing; Direct protein sequencing; Glycoprotein; KW Glycosyltransferase; Golgi apparatus; Lipid metabolism; Membrane; KW Proteomics identification; Reference proteome; Secreted; Signal-anchor; KW Transferase; Transmembrane; 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 FT alpha(1,3)-fucosyltransferase deficiency and no clinically FT relevant phenotype; results in partial enzyme inactivation; FT complete enzyme inactivation when associated with V-244 and FT G-303; 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 FT alpha(1,3)-fucosyltransferase deficiency and no clinically FT relevant phenotype; complete enzyme inactivation when FT associated 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 FT alpha(1,3)-fucosyltransferase deficiency and no clinically FT relevant phenotype; complete enzyme inactivation; FT 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 FT alpha(1,3)-fucosyltransferase deficiency and no clinically FT relevant phenotype; complete enzyme inactivation when FT associated 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 FT I-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 FT I-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 FT T-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 FT T-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 //