ID   FUCT1_HUMAN             Reviewed;         364 AA.
AC   Q96A29; B2RDB2; Q9BV76; Q9NUJ8;
DT   23-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   27-MAR-2024, entry version 185.
DE   RecName: Full=GDP-fucose transporter 1 {ECO:0000305};
DE   AltName: Full=Solute carrier family 35 member C1;
GN   Name=SLC35C1 {ECO:0000312|HGNC:HGNC:20197};
GN   Synonyms=FUCT1 {ECO:0000303|PubMed:27738779};
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, VARIANT CDG2C CYS-147,
RP   CHARACTERIZATION OF VARIANT CDG2C CYS-147, INVOLVEMENT IN CDG2C, AND
RP   SUBCELLULAR LOCATION.
RX   PubMed=11326279; DOI=10.1038/ng0501-69;
RA   Luehn K., Wild M.K., Eckhardt M., Gerardy-Schahn R., Vestweber D.;
RT   "The gene defective in leukocyte adhesion deficiency II encodes a putative
RT   GDP-fucose transporter.";
RL   Nat. Genet. 28:69-72(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, VARIANTS CDG2C CYS-147
RP   AND ARG-308, CHARACTERIZATION OF VARIANT CDG2C CYS-147, INVOLVEMENT IN
RP   CDG2C, SUBCELLULAR LOCATION, AND TRANSPORTER ACTIVITY.
RX   PubMed=11326280; DOI=10.1038/ng0501-73;
RA   Luebke T., Marquardt T., Etzioni A., Hartmann E., von Figura K.,
RA   Koerner C.;
RT   "Complementation cloning identifies CDG-IIc, a new type of congenital
RT   disorders of glycosylation, as a GDP-fucose transporter deficiency.";
RL   Nat. Genet. 28:73-76(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC   TISSUE=Mammary gland, and Placenta;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
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   [5]
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   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT SER-49.
RC   TISSUE=Placenta;
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   [7]
RP   FUNCTION, TRANSPORTER ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP   SUBCELLULAR LOCATION.
RX   PubMed=27738779; DOI=10.1007/s10529-016-2233-x;
RA   Foerster-Fromme K., Schneider S., Sprenger G.A., Albermann C.;
RT   "Functional expression of a human GDP-L-fucose transporter in Escherichia
RT   coli.";
RL   Biotechnol. Lett. 39:219-226(2017).
CC   -!- FUNCTION: Antiporter specific for GDP-l-fucose and depending on the
CC       concomitant reverse transport of GMP. Involved in GDP-fucose import
CC       from the cytoplasm into the Golgi lumen. {ECO:0000269|PubMed:11326279,
CC       ECO:0000269|PubMed:11326280, ECO:0000269|PubMed:27738779}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=GDP-beta-L-fucose(in) + GMP(out) = GDP-beta-L-fucose(out) +
CC         GMP(in); Xref=Rhea:RHEA:72707, ChEBI:CHEBI:57273, ChEBI:CHEBI:58115;
CC         Evidence={ECO:0000269|PubMed:11326280, ECO:0000269|PubMed:27738779};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=4 uM for GDP-beta-L-fucose {ECO:0000269|PubMed:27738779};
CC         Vmax=8 pmol/min/mg enzyme {ECO:0000269|PubMed:27738779};
CC   -!- SUBCELLULAR LOCATION: Golgi apparatus membrane
CC       {ECO:0000305|PubMed:11326279, ECO:0000305|PubMed:11326280,
CC       ECO:0000305|PubMed:27738779}; Multi-pass membrane protein
CC       {ECO:0000255}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=Q96A29-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q96A29-2; Sequence=VSP_047116;
CC   -!- DISEASE: Congenital disorder of glycosylation 2C (CDG2C) [MIM:266265]:
CC       A multisystem disorder caused by a defect in glycoprotein biosynthesis
CC       and characterized by under-glycosylated serum glycoproteins. Congenital
CC       disorders of glycosylation result in a wide variety of clinical
CC       features, such as defects in the nervous system development,
CC       psychomotor retardation, dysmorphic features, hypotonia, coagulation
CC       disorders, and immunodeficiency. The broad spectrum of features
CC       reflects the critical role of N-glycoproteins during embryonic
CC       development, differentiation, and maintenance of cell functions. The
CC       clinical features of CDG2C include intellectual disability, short
CC       stature, facial stigmata, and recurrent bacterial peripheral infections
CC       with persistently elevated peripheral leukocytes. Biochemically, CDG2C
CC       is characterized by a lack of fucosylated glycoconjugates, including
CC       selectin ligands. {ECO:0000269|PubMed:11326279,
CC       ECO:0000269|PubMed:11326280}. Note=The disease is caused by variants
CC       affecting the gene represented in this entry.
CC   -!- SIMILARITY: Belongs to the TPT transporter family. SLC35C subfamily.
CC       {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=SLC35C1base; Note=SLC35C1 mutation db;
CC       URL="http://structure.bmc.lu.se/idbase/SLC35C1base/";
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DR   EMBL; AF323970; AAK50397.1; -; mRNA.
DR   EMBL; AF326199; AAK51705.1; -; mRNA.
DR   EMBL; AK027394; BAB55080.1; -; mRNA.
DR   EMBL; AK002182; BAA92126.1; -; mRNA.
DR   EMBL; AK315473; BAG37859.1; -; mRNA.
DR   EMBL; AC044839; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471064; EAW68031.1; -; Genomic_DNA.
DR   EMBL; BC001427; AAH01427.2; -; mRNA.
DR   CCDS; CCDS44575.1; -. [Q96A29-2]
DR   CCDS; CCDS7914.1; -. [Q96A29-1]
DR   RefSeq; NP_001138737.1; NM_001145265.1. [Q96A29-2]
DR   RefSeq; NP_001138738.1; NM_001145266.1. [Q96A29-2]
DR   RefSeq; NP_060859.4; NM_018389.4. [Q96A29-1]
DR   AlphaFoldDB; Q96A29; -.
DR   SMR; Q96A29; -.
DR   BioGRID; 120624; 10.
DR   IntAct; Q96A29; 2.
DR   STRING; 9606.ENSP00000313318; -.
DR   TCDB; 2.A.7.16.1; the drug/metabolite transporter (dmt) superfamily.
DR   iPTMnet; Q96A29; -.
DR   PhosphoSitePlus; Q96A29; -.
DR   SwissPalm; Q96A29; -.
DR   BioMuta; SLC35C1; -.
DR   DMDM; 20138280; -.
DR   jPOST; Q96A29; -.
DR   MassIVE; Q96A29; -.
DR   MaxQB; Q96A29; -.
DR   PaxDb; 9606-ENSP00000313318; -.
DR   PeptideAtlas; Q96A29; -.
DR   ProteomicsDB; 3427; -.
DR   ProteomicsDB; 75900; -. [Q96A29-1]
DR   Pumba; Q96A29; -.
DR   Antibodypedia; 13252; 65 antibodies from 20 providers.
DR   DNASU; 55343; -.
DR   Ensembl; ENST00000314134.4; ENSP00000313318.3; ENSG00000181830.9. [Q96A29-1]
DR   Ensembl; ENST00000442528.2; ENSP00000412408.2; ENSG00000181830.9. [Q96A29-2]
DR   Ensembl; ENST00000526817.2; ENSP00000432145.2; ENSG00000181830.9. [Q96A29-2]
DR   GeneID; 55343; -.
DR   KEGG; hsa:55343; -.
DR   MANE-Select; ENST00000314134.4; ENSP00000313318.3; NM_018389.5; NP_060859.4.
DR   UCSC; uc001nbo.4; human. [Q96A29-1]
DR   AGR; HGNC:20197; -.
DR   CTD; 55343; -.
DR   DisGeNET; 55343; -.
DR   GeneCards; SLC35C1; -.
DR   HGNC; HGNC:20197; SLC35C1.
DR   HPA; ENSG00000181830; Tissue enhanced (liver).
DR   MalaCards; SLC35C1; -.
DR   MIM; 266265; phenotype.
DR   MIM; 605881; gene.
DR   neXtProt; NX_Q96A29; -.
DR   OpenTargets; ENSG00000181830; -.
DR   Orphanet; 99843; Leukocyte adhesion deficiency type II.
DR   PharmGKB; PA134930330; -.
DR   VEuPathDB; HostDB:ENSG00000181830; -.
DR   eggNOG; KOG1442; Eukaryota.
DR   GeneTree; ENSGT00390000013315; -.
DR   HOGENOM; CLU_044894_1_0_1; -.
DR   InParanoid; Q96A29; -.
DR   OMA; FITWYQC; -.
DR   OrthoDB; 465at2759; -.
DR   PhylomeDB; Q96A29; -.
DR   TreeFam; TF354269; -.
DR   PathwayCommons; Q96A29; -.
DR   Reactome; R-HSA-5619078; Defective SLC35C1 causes congenital disorder of glycosylation 2C (CDG2C).
DR   Reactome; R-HSA-6787639; GDP-fucose biosynthesis.
DR   Reactome; R-HSA-727802; Transport of nucleotide sugars.
DR   SignaLink; Q96A29; -.
DR   BioGRID-ORCS; 55343; 31 hits in 1155 CRISPR screens.
DR   ChiTaRS; SLC35C1; human.
DR   GeneWiki; SLC35C1; -.
DR   GenomeRNAi; 55343; -.
DR   Pharos; Q96A29; Tbio.
DR   PRO; PR:Q96A29; -.
DR   Proteomes; UP000005640; Chromosome 11.
DR   RNAct; Q96A29; Protein.
DR   Bgee; ENSG00000181830; Expressed in lower esophagus mucosa and 175 other cell types or tissues.
DR   ExpressionAtlas; Q96A29; baseline and differential.
DR   GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR   GO; GO:0000139; C:Golgi membrane; IDA:UniProtKB.
DR   GO; GO:0015297; F:antiporter activity; IBA:GO_Central.
DR   GO; GO:0005457; F:GDP-fucose transmembrane transporter activity; IDA:UniProtKB.
DR   GO; GO:0008643; P:carbohydrate transport; IEA:UniProtKB-KW.
DR   GO; GO:0036085; P:GDP-fucose import into Golgi lumen; IDA:UniProtKB.
DR   GO; GO:0030259; P:lipid glycosylation; IEA:Ensembl.
DR   GO; GO:0045746; P:negative regulation of Notch signaling pathway; IEA:Ensembl.
DR   GO; GO:0036066; P:protein O-linked fucosylation; IBA:GO_Central.
DR   InterPro; IPR004853; Sugar_P_trans_dom.
DR   PANTHER; PTHR11132:SF255; GDP-FUCOSE TRANSPORTER 1; 1.
DR   PANTHER; PTHR11132; SOLUTE CARRIER FAMILY 35; 1.
DR   Pfam; PF03151; TPT; 1.
DR   Genevisible; Q96A29; HS.
PE   1: Evidence at protein level;
KW   Alternative splicing; Congenital disorder of glycosylation;
KW   Disease variant; Golgi apparatus; Membrane; Reference proteome;
KW   Sugar transport; Transmembrane; Transmembrane helix; Transport.
FT   CHAIN           1..364
FT                   /note="GDP-fucose transporter 1"
FT                   /id="PRO_0000213391"
FT   TRANSMEM        34..56
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        76..98
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        111..130
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        140..162
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        167..185
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        195..214
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        227..249
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        264..286
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   VAR_SEQ         1..13
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:14702039"
FT                   /id="VSP_047116"
FT   VARIANT         49
FT                   /note="W -> S (in dbSNP:rs11538193)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_057302"
FT   VARIANT         147
FT                   /note="R -> C (in CDG2C; does not rescue defective
FT                   fucosylation in cells lacking GDP-fucose transport;
FT                   dbSNP:rs28939087)"
FT                   /evidence="ECO:0000269|PubMed:11326279,
FT                   ECO:0000269|PubMed:11326280"
FT                   /id="VAR_012347"
FT   VARIANT         240
FT                   /note="I -> V (in dbSNP:rs7130656)"
FT                   /id="VAR_057303"
FT   VARIANT         308
FT                   /note="T -> R (in CDG2C; dbSNP:rs28937886)"
FT                   /evidence="ECO:0000269|PubMed:11326280"
FT                   /id="VAR_012348"
FT   CONFLICT        258
FT                   /note="F -> L (in Ref. 3; BAA92126)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   364 AA;  39809 MW;  2E659D49C5C5E92E CRC64;
     MNRAPLKRSR ILHMALTGAS DPSAEAEANG EKPFLLRALQ IALVVSLYWV TSISMVFLNK
     YLLDSPSLRL DTPIFVTFYQ CLVTTLLCKG LSALAACCPG AVDFPSLRLD LRVARSVLPL
     SVVFIGMITF NNLCLKYVGV AFYNVGRSLT TVFNVLLSYL LLKQTTSFYA LLTCGIIIGG
     FWLGVDQEGA EGTLSWLGTV FGVLASLCVS LNAIYTTKVL PAVDGSIWRL TFYNNVNACI
     LFLPLLLLLG ELQALRDFAQ LGSAHFWGMM TLGGLFGFAI GYVTGLQIKF TSPLTHNVSG
     TAKACAQTVL AVLYYEETKS FLWWTSNMMV LGGSSAYTWV RGWEMKKTPE EPSPKDSEKS
     AMGV
//