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2.A.1.1.28
Meyer et al. 2018 The erythrocyte/brain hexose facilitator, glucose transporter-1, Gtr1 or Glut1. Transports D-glucose, dehydroascorbate, arsenite and the flavonone, quercetin, via one pathway and water via a distinct channel. Sugar transport has been suggested to function via a sliding mechanism involving several sugar binding sites (Cunningham et al., 2006). Glut1 is the receptor for human T-cell leukemia virus (HTLV)) (Manel et al., 2003). It is regulated by stomatin (TC# 8.A.21) to take up dehydroascorbate (Montel-Hagen et al., 2008). Mutations cause Glut1 deficiency syndrome, a human encephalopathy that results from decreased glucose flux through the blood brain barrier (Pascual et al., 2008).  Mueckler and Makepeace (2009) have presented a model of the exofacial substrate-binding site and helical folding of Glut1. Glut1, 2, 4 and 9 are functional both in the plasma membrane and the endoplasmic reticulum (Takanaga and Frommer, 2010). Glut1 is down-regulated in the brains of Alzheimer's disease patients (Liu et al., 2008b). Metabolic stress rapidly stimulates blood-brain barrier endothelial cell sugar transport by acute up-regulation of plasma membrane GLUT1 levels, possibly involving an AMP-activated kinase activity (Cura and Carruthers, 2010). Serves as a receptor for neuropilin-1 (923aas; 2 TMSs; O14786) and heparan sulfate proteoglycans (HSPGs) (Hoshino, 2012). Glut1 has a nucleotide binding site, and nucleotide binding affects transport activity (Yao and Bajjalieh 2009).  The protein serves as a receptor for dermatin and β-adducin which help link the spectrin-actin junctional complex to the erythrocyte plasma membrane (Khan et al. 2008).  May play a role in paroxysmal dyskinesias (Erro et al. 2017). GLUT1 mediates infection of CD4+ lymphocytes by human T cell leukemia virus type 1 (Jin et al. 2006). Mutations in disordered regions can cause disease by introducing dileucine motifs, For example, mutations that are causative of GLUT1 deficiency syndrome are of this type and the mutated protein mislocalizes to intracellular compartments (Meyer et al. 2018).

Accession Number:P11166
Protein Name:Gtr1 aka SLC2A1 aka GLUT1
Length:492
Molecular Weight:54084.00
Species:Homo sapiens (Human) [9606]
Number of TMSs:12
Location1 / Topology2 / Orientation3: Cell membrane1 / Multi-pass membrane protein2
Substrate Quercetin, Dehydroascorbate, arsenite, D-glucose

Cross database links:

Genevestigator: P11166 P11166
eggNOG: prNOG04801 COG0477
DIP: DIP-23N DIP-23N
RefSeq: NP_006507.2   
Entrez Gene ID: 6513   
Pfam: PF00083   
OMIM: 138140  gene
606777  phenotype
612126  phenotype
KEGG: hsa:6513    hsa:6513   

Gene Ontology

GO:0016021 C:integral to membrane
GO:0042470 C:melanosome
GO:0005624 C:membrane fraction
GO:0015758 P:glucose transport
GO:0055085 P:transmembrane transport
GO:0016323 C:basolateral plasma membrane
GO:0005901 C:caveola
GO:0005911 C:cell-cell junction
GO:0001939 C:female pronucleus
GO:0030496 C:midbody
GO:0005886 C:plasma membrane
GO:0055056 F:D-glucose transmembrane transporter activity
GO:0033300 F:dehydroascorbic acid transporter activity
GO:0005355 F:glucose transmembrane transporter activity
GO:0042910 F:xenobiotic transporter activity
GO:0005975 P:carbohydrate metabolic process
GO:0042149 P:cellular response to glucose starvation
GO:0006112 P:energy reserve metabolic process
GO:0019852 P:L-ascorbic acid metabolic process
GO:0050796 P:regulation of insulin secretion
GO:0006970 P:response to osmotic stress

References (36)

[1] “Sequence and structure of a human glucose transporter.”  Mueckler M.et.al.   3839598
[2] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[3] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[4] “Characterization and expression of human HepG2/erythrocyte glucose-transporter gene.”  Fukumoto H.et.al.   2834252
[5] “Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes.”  Chi A.et.al.   17081065
[6] “ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.”  Matsuoka S.et.al.   17525332
[7] “Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins.”  Wollscheid B.et.al.   19349973
[8] “Defective glucose transport across brain tissue barriers: a newly recognized neurological syndrome.”  Klepper J.et.al.   10227690
[9] “Mutational analysis of GLUT1 (SLC2A1) in Glut-1 deficiency syndrome.”  Wang D.et.al.   10980529
[10] “Autosomal dominant Glut-1 deficiency syndrome and familial epilepsy.”  Brockmann K.et.al.   11603379
[11] “Autosomal dominant transmission of GLUT1 deficiency.”  Klepper J.et.al.   11136715
[12] “Imaging the metabolic footprint of Glut1 deficiency on the brain.”  Pascual J.M.et.al.   12325075
[13] “GLUT-1 deficiency without epilepsy -- an exceptional case.”  Overweg-Plandsoen W.C.G.et.al.   14605501
[14] “Glut-1 deficiency syndrome: clinical, genetic, and therapeutic aspects.”  Wang D.et.al.   15622525
[15] “GLUT1 mutations are a cause of paroxysmal exertion-induced dyskinesias and induce hemolytic anemia by a cation leak.”  Weber Y.G.et.al.   18451999
[16] “Sequence and structure of a human glucose transporter.”  Mueckler M.et.al.   3839598
[17] “Complete sequencing and characterization of 21,243 full-length human cDNAs.”  Ota T.et.al.   14702039
[18] “The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).”  The MGC Project Teamet.al.   15489334
[19] “Characterization and expression of human HepG2/erythrocyte glucose-transporter gene.”  Fukumoto H.et.al.   2834252
[20] “Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes.”  Chi A.et.al.   17081065
[21] “ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.”  Matsuoka S.et.al.   17525332
[22] “Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins.”  Wollscheid B.et.al.   19349973
[23] “Defective glucose transport across brain tissue barriers: a newly recognized neurological syndrome.”  Klepper J.et.al.   10227690
[24] “Mutational analysis of GLUT1 (SLC2A1) in Glut-1 deficiency syndrome.”  Wang D.et.al.   10980529
[25] “Autosomal dominant Glut-1 deficiency syndrome and familial epilepsy.”  Brockmann K.et.al.   11603379
[26] “Autosomal dominant transmission of GLUT1 deficiency.”  Klepper J.et.al.   11136715
[27] “Imaging the metabolic footprint of Glut1 deficiency on the brain.”  Pascual J.M.et.al.   12325075
[28] “GLUT-1 deficiency without epilepsy -- an exceptional case.”  Overweg-Plandsoen W.C.G.et.al.   14605501
[29] “Glut-1 deficiency syndrome: clinical, genetic, and therapeutic aspects.”  Wang D.et.al.   15622525
[30] “GLUT1 mutations are a cause of paroxysmal exertion-induced dyskinesias and induce hemolytic anemia by a cation leak.”  Weber Y.G.et.al.   18451999
[31] “Early-onset absence epilepsy caused by mutations in the glucose transporter GLUT1.”  Suls A.et.al.   19798636
[32] “Glucose transporter-1 deficiency syndrome: the expanding clinical and genetic spectrum of a treatable disorder.”  Leen W.G.et.al.   20129935
[33] “Mild adolescent/adult onset epilepsy and paroxysmal exercise-induced dyskinesia due to GLUT1 deficiency.”  Afawi Z.et.al.   21204808
[34] “Paroxysmal exercise-induced dyskinesia, writer's cramp, migraine with aura and absence epilepsy in twin brothers with a novel SLC2A1 missense mutation.”  Urbizu A.et.al.   20621801
[35] “Absence epilepsies with widely variable onset are a key feature of familial GLUT1 deficiency.”  Mullen S.A.et.al.   20574033
[36] “Excellent response to acetazolamide in a case of paroxysmal dyskinesias due to GLUT1-deficiency.”  Anheim M.et.al.   20830593
Structure:
1SUK   4PYP   5eqg     

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FASTA formatted sequence
1:	MEPSSKKLTG RLMLAVGGAV LGSLQFGYNT GVINAPQKVI EEFYNQTWVH RYGESILPTT 
61:	LTTLWSLSVA IFSVGGMIGS FSVGLFVNRF GRRNSMLMMN LLAFVSAVLM GFSKLGKSFE 
121:	MLILGRFIIG VYCGLTTGFV PMYVGEVSPT ALRGALGTLH QLGIVVGILI AQVFGLDSIM 
181:	GNKDLWPLLL SIIFIPALLQ CIVLPFCPES PRFLLINRNE ENRAKSVLKK LRGTADVTHD 
241:	LQEMKEESRQ MMREKKVTIL ELFRSPAYRQ PILIAVVLQL SQQLSGINAV FYYSTSIFEK 
301:	AGVQQPVYAT IGSGIVNTAF TVVSLFVVER AGRRTLHLIG LAGMAGCAIL MTIALALLEQ 
361:	LPWMSYLSIV AIFGFVAFFE VGPGPIPWFI VAELFSQGPR PAAIAVAGFS NWTSNFIVGM 
421:	CFQYVEQLCG PYVFIIFTVL LVLFFIFTYF KVPETKGRTF DEIASGFRQG GASQSDKTPE 
481:	ELFHPLGADS QV