FUT4_HUMAN
ID FUT4_HUMAN Reviewed; 530 AA.
AC P22083; B2RMS0;
DT 01-AUG-1991, integrated into UniProtKB/Swiss-Prot.
DT 14-APR-2009, sequence version 3.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=Alpha-(1,3)-fucosyltransferase 4;
DE AltName: Full=4-galactosyl-N-acetylglucosaminide 3-alpha-L-fucosyltransferase;
DE EC=2.4.1.152 {ECO:0000269|PubMed:1716630, ECO:0000269|PubMed:29593094};
DE AltName: Full=ELAM-1 ligand fucosyltransferase {ECO:0000303|PubMed:1702034};
DE AltName: Full=Fucosyltransferase 4;
DE AltName: Full=Fucosyltransferase IV;
DE Short=Fuc-TIV;
DE Short=FucT-IV;
DE AltName: Full=Galactoside 3-L-fucosyltransferase;
GN Name=FUT4 {ECO:0000303|PubMed:29593094};
GN Synonyms=ELFT {ECO:0000303|PubMed:1702034}, 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] (ISOFORMS LONG AND SHORT), AND FUNCTION (ISOFORM
RP SHORT).
RX PubMed=1702034; DOI=10.1016/0092-8674(90)90430-m;
RA Goelz S.E., Hession C., Goff D., Griffiths B., Tizard R., Newman B.,
RA Chi-Rosso G., Lobb R.;
RT "ELFT: a gene that directs the expression of an ELAM-1 ligand.";
RL Cell 63:1349-1356(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION (ISOFORM SHORT), AND CATALYTIC
RP ACTIVITY (ISOFORM SHORT).
RC TISSUE=Peripheral blood leukocyte;
RX PubMed=1716630; DOI=10.1016/s0021-9258(19)47396-1;
RA Lowe J.B., Kukowska-Latallo J.F., Nair R.P., Larsen R.D., Marks R.M.,
RA Macher B.A., Kelly R.J., Ernst L.K.;
RT "Molecular cloning of a human fucosyltransferase gene that determines
RT expression of the Lewis x and VIM-2 epitopes but not ELAM-1-dependent cell
RT adhesion.";
RL J. Biol. Chem. 266:17467-17477(1991).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16554811; DOI=10.1038/nature04632;
RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K.,
RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T.,
RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G.,
RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C.,
RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A.,
RA Hattori M., Rogers J., Lander E.S., Sakaki Y.;
RT "Human chromosome 11 DNA sequence and analysis including novel gene
RT identification.";
RL Nature 440:497-500(2006).
RN [4]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 126-525.
RX PubMed=1718983; DOI=10.1016/s0021-9258(18)54704-9;
RA Kumar R., Potvin B., Muller W.A., Stanley P.;
RT "Cloning of a human alpha(1,3)-fucosyltransferase gene that encodes ELFT
RT but does not confer ELAM-1 recognition on Chinese hamster ovary cell
RT transfectants.";
RL J. Biol. Chem. 266:21777-21783(1991).
RN [7]
RP FUNCTION (ISOFORM SHORT), CATALYTIC ACTIVITY (ISOFORM SHORT), AND TISSUE
RP SPECIFICITY.
RX PubMed=11278338; DOI=10.1074/jbc.m007272200;
RA Nakayama F., Nishihara S., Iwasaki H., Kudo T., Okubo R., Kaneko M.,
RA Nakamura M., Karube M., Sasaki K., Narimatsu H.;
RT "CD15 expression in mature granulocytes is determined by alpha 1,3-
RT fucosyltransferase IX, but in promyelocytes and monocytes by alpha 1,3-
RT fucosyltransferase IV.";
RL J. Biol. Chem. 276:16100-16106(2001).
RN [8]
RP FUNCTION (ISOFORMS LONG AND SHORT), CATALYTIC ACTIVITY (ISOFORM SHORT),
RP PATHWAY (ISOFORM SHORT), AND TISSUE SPECIFICITY (ISOFORM SHORT).
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).
CC -!- FUNCTION: [Isoform Short]: Catalyzes alpha(1->3) linkage of fucosyl
CC moiety transferred from GDP-beta-L-fucose to N-acetyl glucosamine
CC (GlcNAc) within type 2 lactosamine (LacNAc, Gal-beta(1->4)GlcNAc)
CC glycan attached to N- or O-linked glycoproteins (PubMed:29593094,
CC PubMed:1702034, PubMed:1716630). Robustly fucosylates nonsialylated
CC distal LacNAc unit of the polylactosamine chain to form Lewis X antigen
CC (CD15), a glycan determinant known to mediate important cellular
CC functions in development and immunity. Fucosylates with lower
CC efficiency sialylated LacNAc acceptors to form sialyl Lewis X and 6-
CC sulfo sialyl Lewis X determinants that serve as recognition epitopes
CC for C-type lectins (PubMed:29593094, PubMed:1716630). Together with
CC FUT7 contributes to SELE, SELL and SELP selectin ligand biosynthesis
CC and selectin-dependent lymphocyte homing, leukocyte migration and blood
CC leukocyte homeostasis (By similarity). In a cell type specific manner,
CC may also fucosylate the internal LacNAc unit of the polylactosamine
CC chain to form VIM-2 antigen that serves as recognition epitope for SELE
CC (PubMed:1716630, PubMed:11278338). {ECO:0000250|UniProtKB:Q11127,
CC ECO:0000269|PubMed:1702034, ECO:0000269|PubMed:1716630,
CC ECO:0000269|PubMed:29593094}.
CC -!- FUNCTION: [Isoform Long]: Does not generate Lewis X antigens.
CC {ECO:0000269|PubMed:29593094}.
CC -!- CATALYTIC ACTIVITY: [Isoform Short]:
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:1716630,
CC ECO:0000269|PubMed:29593094};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:14258;
CC Evidence={ECO:0000269|PubMed:1716630};
CC -!- CATALYTIC ACTIVITY: [Isoform Short]:
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:0000269|PubMed:29593094};
CC -!- CATALYTIC ACTIVITY: [Isoform Short]:
CC Reaction=an alpha-Neu5Ac-(2->3)-beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->3)-
CC beta-D-Gal-(1->4)-beta-D-GlcNAc derivative + GDP-beta-L-fucose = an
CC alpha-Neu5Ac-(2->3)-beta-D-Gal-(1->4)-beta-D-GlcNAc-(1->3)-beta-D-
CC Gal-(1->4)-[alpha-L-Fuc-(1->3)]-beta-D-GlcNAc derivative + GDP +
CC H(+); Xref=Rhea:RHEA:68044, ChEBI:CHEBI:15378, ChEBI:CHEBI:57273,
CC ChEBI:CHEBI:58189, ChEBI:CHEBI:145343, ChEBI:CHEBI:176900;
CC Evidence={ECO:0000269|PubMed:11278338, ECO:0000269|PubMed:1716630};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:68045;
CC Evidence={ECO:0000305|PubMed:11278338, ECO:0000305|PubMed:1716630};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=an alpha-Neu5Ac-(2->3)-beta-D-Gal-(1->4)-beta-D-GlcNAc6S
CC derivative + GDP-beta-L-fucose = an alpha-Neu5Ac-(2->3)-beta-D-Gal-
CC (1->4)-[alpha-L-Fuc-(1->3)]-beta-D-GlcNAc6S derivative + GDP + H(+);
CC Xref=Rhea:RHEA:62004, ChEBI:CHEBI:15378, ChEBI:CHEBI:57273,
CC ChEBI:CHEBI:58189, ChEBI:CHEBI:145344, ChEBI:CHEBI:145345;
CC Evidence={ECO:0000250|UniProtKB:Q11127};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62005;
CC Evidence={ECO:0000250|UniProtKB:Q11127};
CC -!- PATHWAY: [Isoform Short]: Protein modification; protein glycosylation.
CC {ECO:0000269|PubMed:29593094}.
CC -!- SUBCELLULAR LOCATION: Golgi apparatus, Golgi stack membrane; Single-
CC pass type II membrane protein. Note=Membrane-bound form in trans
CC cisternae of Golgi.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative initiation; Named isoforms=2;
CC Name=Long {ECO:0000303|PubMed:29593094}; Synonyms=ELFT-L
CC {ECO:0000303|PubMed:1702034};
CC IsoId=P22083-1; Sequence=Displayed;
CC Name=Short {ECO:0000303|PubMed:29593094}; Synonyms=ELFT
CC {ECO:0000303|PubMed:1702034};
CC IsoId=P22083-2; Sequence=VSP_061247;
CC -!- TISSUE SPECIFICITY: [Isoform Short]: Expressed at low levels in bone
CC marrow-derived mesenchymal stem cells. {ECO:0000269|PubMed:29593094}.
CC -!- TISSUE SPECIFICITY: Expressed in cord blood immature promyelocytes and
CC in peripheral blood myeloid and lymphoid cell populations.
CC {ECO:0000269|PubMed:11278338}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 10 family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB20349.1; Type=Frameshift; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - GTase;
CC Note=Fucosyltransferase 4;
CC URL="http://www.functionalglycomics.org/glycomics/molecule/jsp/glycoEnzyme/viewGlycoEnzyme.jsp?gbpId=gt_hum_601";
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DR EMBL; M58596; AAA63172.1; -; mRNA.
DR EMBL; M58597; AAA63173.1; -; mRNA.
DR EMBL; M65030; AAA92977.1; -; Genomic_DNA.
DR EMBL; AP000943; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471065; EAW66938.1; -; Genomic_DNA.
DR EMBL; BC136373; AAI36374.1; -; mRNA.
DR EMBL; BC136374; AAI36375.1; -; mRNA.
DR EMBL; S65161; AAB20349.1; ALT_SEQ; Genomic_DNA.
DR CCDS; CCDS8301.1; -. [P22083-1]
DR PIR; B36340; B36340.
DR RefSeq; NP_002024.1; NM_002033.3.
DR AlphaFoldDB; P22083; -.
DR BioGRID; 108802; 8.
DR IntAct; P22083; 2.
DR MINT; P22083; -.
DR STRING; 9606.ENSP00000351602; -.
DR ChEMBL; CHEMBL4996; -.
DR CAZy; GT10; Glycosyltransferase Family 10.
DR GlyGen; P22083; 2 sites.
DR iPTMnet; P22083; -.
DR PhosphoSitePlus; P22083; -.
DR BioMuta; FUT4; -.
DR DMDM; 226694189; -.
DR EPD; P22083; -.
DR jPOST; P22083; -.
DR MassIVE; P22083; -.
DR MaxQB; P22083; -.
DR PaxDb; P22083; -.
DR PeptideAtlas; P22083; -.
DR PRIDE; P22083; -.
DR ProteomicsDB; 53958; -.
DR Antibodypedia; 3496; 1963 antibodies from 46 providers.
DR DNASU; 2526; -.
DR Ensembl; ENST00000358752.4; ENSP00000351602.2; ENSG00000196371.4. [P22083-1]
DR GeneID; 2526; -.
DR KEGG; hsa:2526; -.
DR MANE-Select; ENST00000358752.4; ENSP00000351602.2; NM_002033.4; NP_002024.1.
DR UCSC; uc001pez.4; human. [P22083-1]
DR CTD; 2526; -.
DR DisGeNET; 2526; -.
DR GeneCards; FUT4; -.
DR HGNC; HGNC:4015; FUT4.
DR HPA; ENSG00000196371; Tissue enriched (bone).
DR MIM; 104230; gene.
DR neXtProt; NX_P22083; -.
DR OpenTargets; ENSG00000196371; -.
DR PharmGKB; PA28431; -.
DR VEuPathDB; HostDB:ENSG00000196371; -.
DR eggNOG; KOG2619; Eukaryota.
DR GeneTree; ENSGT00940000162506; -.
DR HOGENOM; CLU_032075_4_0_1; -.
DR InParanoid; P22083; -.
DR OMA; ANYERFM; -.
DR OrthoDB; 551308at2759; -.
DR PhylomeDB; P22083; -.
DR TreeFam; TF316348; -.
DR BioCyc; MetaCyc:HS07593-MON; -.
DR BRENDA; 2.4.1.152; 2681.
DR PathwayCommons; P22083; -.
DR Reactome; R-HSA-9037629; Lewis blood group biosynthesis.
DR SignaLink; P22083; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 2526; 24 hits in 1091 CRISPR screens.
DR GenomeRNAi; 2526; -.
DR Pharos; P22083; Tbio.
DR PRO; PR:P22083; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; P22083; protein.
DR Bgee; ENSG00000196371; Expressed in mucosa of sigmoid colon and 139 other tissues.
DR Genevisible; P22083; HS.
DR GO; GO:0071944; C:cell periphery; IEA:Ensembl.
DR GO; GO:0009986; C:cell surface; IEA:Ensembl.
DR GO; GO:0005794; C:Golgi apparatus; TAS: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; TAS:ProtInc.
DR GO; GO:0005802; C:trans-Golgi network; 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; IBA:GO_Central.
DR GO; GO:0008417; F:fucosyltransferase activity; TAS:ProtInc.
DR GO; GO:0005975; P:carbohydrate metabolic process; TAS:ProtInc.
DR GO; GO:0036065; P:fucosylation; IBA:GO_Central.
DR GO; GO:0006688; P:glycosphingolipid biosynthetic process; IDA:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IEA:UniProtKB-KW.
DR GO; GO:0042355; P:L-fucose catabolic process; NAS:UniProtKB.
DR GO; GO:0097022; P:lymphocyte migration into lymph node; ISS:UniProtKB.
DR GO; GO:0009312; P:oligosaccharide biosynthetic process; TAS:Reactome.
DR GO; GO:0009311; P:oligosaccharide metabolic process; IDA:UniProtKB.
DR GO; GO:1903238; P:positive regulation of leukocyte tethering or rolling; ISS:UniProtKB.
DR GO; GO:1902624; P:positive regulation of neutrophil migration; ISS:UniProtKB.
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 GO; GO:1903037; P:regulation of leukocyte cell-cell adhesion; 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 Alternative initiation; Glycoprotein; Glycosyltransferase; Golgi apparatus;
KW Inflammatory response; Membrane; Reference proteome; Signal-anchor;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..530
FT /note="Alpha-(1,3)-fucosyltransferase 4"
FT /id="PRO_0000221100"
FT TOPO_DOM 1..147
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT TRANSMEM 148..172
FT /note="Helical; Signal-anchor for type II membrane protein"
FT /evidence="ECO:0000255"
FT TOPO_DOM 173..530
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT REGION 1..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 66..112
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 88..102
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 216
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 315
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VAR_SEQ 1..125
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000269|PubMed:1702034"
FT /id="VSP_061247"
FT VARIANT 255
FT /note="I -> V (in dbSNP:rs2230273)"
FT /id="VAR_055844"
FT CONFLICT 212
FT /note="R -> P (in Ref. 2; AAA92977)"
FT /evidence="ECO:0000305"
FT CONFLICT 366
FT /note="E -> D (in Ref. 6; AAB20349)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 530 AA; 59084 MW; B10C1C3C67BE1562 CRC64;
MRRLWGAARK PSGAGWEKEW AEAPQEAPGA WSGRLGPGRS GRKGRAVPGW ASWPAHLALA
ARPARHLGGA GQGPRPLHSG TAPFHSRASG ERQRRLEPQL QHESRCRSST PADAWRAEAA
LPVRAMGAPW GSPTAAAGGR RGWRRGRGLP WTVCVLAAAG LTCTALITYA CWGQLPPLPW
ASPTPSRPVG VLLWWEPFGG RDSAPRPPPD CRLRFNISGC RLLTDRASYG EAQAVLFHHR
DLVKGPPDWP PPWGIQAHTA EEVDLRVLDY EEAAAAAEAL ATSSPRPPGQ RWVWMNFESP
SHSPGLRSLA SNLFNWTLSY RADSDVFVPY GYLYPRSHPG DPPSGLAPPL SRKQGLVAWV
VSHWDERQAR VRYYHQLSQH VTVDVFGRGG PGQPVPEIGL LHTVARYKFY LAFENSQHLD
YITEKLWRNA LLAGAVPVVL GPDRANYERF VPRGAFIHVD DFPSASSLAS YLLFLDRNPA
VYRRYFHWRR SYAVHITSFW DEPWCRVCQA VQRAGDRPKS IRNLASWFER
