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2.A.1.1.28
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).

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