|Name:||solute carrier family 35, member C1|
|PubMed (11326279):|| Luhn K, Wild MK, Eckhardt M, Gerardy-Schahn R, Vestweber D. The gene defective in leukocyte adhesion deficiency II encodes a putativeGDP-fucose transporter.Nat Genet. 2001 May;28(1):69-72. PMID: 11326279 [PubMed - indexed for MEDLINE]|
Leukocyte adhesion deficiency II (LAD II) is characterized by the lack of fucosylated glycoconjugates, including selectin ligands, causing immunodeficiency and severe mental and growth retardation. No deficiency in fucosyltransferase activities or in the activities of enzymes involved in GDP-fucose biosynthesis has been found. Instead, the transport of GDP-fucose into isolated Golgi vesicles of LAD II cells appeared to be reduced. To identify the gene mutated in LAD II, we cloned 12 cDNAs from Caenorhabditis elegans, encoding multi-spanning transmembrane proteins with homology to known nucleotide sugar transporters, and transfected them into fibroblasts from an LAD II patient. One of these clones re-established expression of fucosylated glycoconjugates with high efficiency and allowed us to identify a human homolog with 55% identity, which also directed re-expression of fucosylated glycoconjugates. Both proteins were localized to the Golgi. The corresponding endogenous protein in LAD II cells had an R147C amino acid change in the conserved fourth transmembrane region. Overexpression of this mutant protein in cells from a patient with LAD II did not rescue fucosylation, demonstrating that the point mutation affected the activity of the protein. Thus, we have identified the first putative GDP-fucose transporter, which has been highly conserved throughout evolution. A point mutation in its gene is responsible for the disease in this patient with LAD II.
|PubMed (11326280):|| Lubke T, Marquardt T, Etzioni A, Hartmann E, von Figura K, Korner C. Complementation cloning identifies CDG-IIc, a new type of congenital disordersof glycosylation, as a GDP-fucose transporter deficiency.Nat Genet. 2001 May;28(1):73-6. PMID: 11326280 [PubMed - indexed for MEDLINE]|
Congenital disorders of glycosylation (CDG) comprise a rapidly growing group of inherited disorders in which glycosylation of glycoproteins is defective due to mutations in genes required for the assembly of lipid-linked oligosaccharides, their transfer to nascent glycoproteins (CDG-I) or the processing of protein-bound glycans (CDG-II). Previously' a defect in the GDP-fucose import into the lumen of the Golgi was identified in a person with CDG (A.C.) with a general deficiency of fucosyl residues in glycoproteins. This patient presents the clinical features of leukocyte adhesion deficiency type II (LAD II) including mental retardation, short stature, facial stigmata, and recurrent bacterial peripheral infections with persistently elevated peripheral leukocytes. Using a fucose-specific, lectin-staining procedure for detection of fucosylated glycoproteins and a retroviral cDNA library, we isolated a cDNA complementing the fucosylation defect in the patient's fibroblasts. The cDNA encodes a highly hydrophobic protein of 364 amino acids with multiple putative transmembrane domains. Restoration of GDP-fucose import activity in Golgi-enriched vesicles from the patient's fibroblasts verified the GDP-fucose transporter activity of this protein. We identified two missense mutations in the GDP-fucose transporter cDNA of patient A.C. and of two other people with LAD II. Thus complementation cloning allowed us to identify the human GDP-fucose transporter cDNA and GDP-fucose transporter deficiency as a cause for a new type of CDG. Following the recent recommendations for the nomenclature for CDG, this new type is classified as CDG-IIc (formerly LAD II).
>sp|Q96A29|FCT1_HUMAN GDP-fucose transporter 1 - Homo sapiens (Human). MNRAPLKRSRILHMALTGASDPSAEAEANGEKPFLLRALQIALVVSLYWVTSISMVFLNKYLLDSPSLRLDTPIFVTFYQ CLVTTLLCKGLSALAACCPGAVDFPSLRLDLRVARSVLPLSVVFIGMITFNNLCLKYVGVAFYNVGRSLTTVFNVLLSYL LLKQTTSFYALLTCGIIIGGFWLGVDQEGAEGTLSWLGTVFGVLASLCVSLNAIYTTKVLPAVDGSIWRLTFYNNVNACI LFLPLLLLLGELQALRDFAQLGSAHFWGMMTLGGLFGFAIGYVTGLQIKFTSPLTHNVSGTAKACAQTVLAVLYYEETKS FLWWTSNMMVLGGSSAYTWVRGWEMKKTPEEPSPKDSEKSAMGV