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{{Short description|Uniporter protein}}
{{Infobox_gene}}
'''Glucose transporter 1''' (or '''GLUT1'''), also known as '''solute carrier family 2, facilitated glucose transporter member 1''' (SLC2A1), is a [[uniporter]] [[protein]] that in humans is encoded by the ''SLC2A1'' [[gene]].<ref name="pmid3839598">{{cite journal | vauthors = Mueckler M, Caruso C, Baldwin SA, Panico M, Blench I, Morris HR, Allard WJ, Lienhard GE, Lodish HF | title = Sequence and structure of a human glucose transporter | journal = Science | volume = 229 | issue = 4717 | pages = 941–5 | date = September 1985 | pmid = 3839598 | doi = 10.1126/science.3839598 | bibcode = 1985Sci...229..941M }}</ref> GLUT1 [[facilitated diffusion|facilitates]] the transport of [[glucose]] across the [[cell membrane|plasma membranes]] of mammalian cells.<ref name="pmid8839927">{{cite journal | vauthors = Olson AL, Pessin JE | title = Structure, function, and regulation of the mammalian facilitative glucose transporter gene family | journal = Annual Review of Nutrition | volume = 16
[[Mutation]]s in this gene can cause [[Glut1 deficiency|GLUT1 deficiency syndrome 1, GLUT1 deficiency syndrome 2]], [[idiopathic generalized epilepsy]] 12, [[dystonia]] 9, and [[Hereditary stomatocytosis#Variants|stomatin-deficient cryohydrocytosis]].<ref name=":0">{{Cite web|url=https://www.uniprot.org/uniprot/P11166|title=SLC2A1 – Solute carrier family 2, facilitated glucose transporter member 1 – Homo sapiens (Human) – SLC2A1 gene & protein|website=www.uniprot.org|language=en|access-date=2018-08-27}}{{CC-notice|cc=by4}}</ref><ref name=":3">{{cite journal | title = UniProt: the universal protein knowledgebase | journal = Nucleic Acids Research | volume = 45 | issue = D1 | pages = D158–D169 | date = January 2017 | pmid = 27899622 | pmc = 5210571 | doi = 10.1093/nar/gkw1099 }}</ref>
== Discovery ==
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== Structure ==
The ''SLC2A1'' gene is located on the p arm of [[chromosome 1]] in position 34.2 and has 10 [[exon]]s spanning 33,802 base pairs.<ref name = "entrez"/> The gene produces a 54.1 kDa protein composed of 492 [[amino acids]].<ref name=COPaKB>{{cite journal | vauthors = Zong NC, Li H, Li H, Lam MP, Jimenez RC, Kim CS, Deng N, Kim AK, Choi JH, Zelaya I, Liem D, Meyer D, Odeberg J, Fang C, Lu HJ, Xu T, Weiss J, Duan H, Uhlen M, Yates JR, Apweiler R, Ge J, Hermjakob H, Ping P | title = Integration of cardiac proteome biology and medicine by a specialized knowledgebase | journal = Circulation Research | volume = 113 | issue = 9 | pages = 1043–53 | date =
GLUT1 behaves as a [[
== Function ==
Energy-yielding metabolism in [[erythrocytes]] depends on a constant supply of glucose from the [[blood plasma]], where the glucose concentration is maintained at about 5mM. Glucose enters the erythrocyte by [[facilitated diffusion]] via a specific glucose transporter, at a rate of about 50,000 times greater than uncatalyzed transmembrane diffusion. The glucose transporter of erythrocytes (called GLUT1 to distinguish it from related glucose transporters in other tissues) is a type III [[integral protein]] with 12 hydrophobic segments, each of which is believed to form a membrane-spanning [[Alpha helix|helix]]. The detailed structure of GLUT1 is not known yet, but one plausible model suggests that the side-by-side assembly of several helices produces a transmembrane [[Ion channel|channel]] lined with hydrophilic residues that can hydrogen-bond with glucose as it moves through the channel.<ref name=Lehninger2008>{{cite book |vauthors=Nelson DL, Cox MM |
GLUT1 is responsible for the low level of basal glucose uptake required to sustain respiration in all cells. Expression levels of GLUT1 in cell membranes are increased by reduced glucose levels and decreased by increased glucose levels.{{citation needed|date=November 2015}}
GLUT1 is also a major receptor for uptake of [[Vitamin C]] as well as [[glucose]], especially in non vitamin C producing mammals as part of an adaptation to compensate by participating in a Vitamin C recycling process. In mammals that do produce Vitamin C, [[GLUT4]] is often expressed instead of GLUT1.<ref name="Amélie2008">{{cite journal | vauthors = Montel-Hagen A, Kinet S, Manel N, Mongellaz C, Prohaska R, Battini JL, Delaunay J, Sitbon M, Taylor N | title = Erythrocyte Glut1 triggers dehydroascorbic acid uptake in mammals unable to synthesize vitamin C | journal = Cell | volume = 132 | issue = 6 | pages = 1039–48 | date = March 2008 | pmid = 18358815 | doi = 10.1016/j.cell.2008.01.042 |
== Tissue distribution ==
GLUT1 expression occurs in almost all tissues, with the degree of expression typically correlating with the rate of cellular glucose metabolism. In the adult it is expressed at highest levels in [[erythrocytes]] and also in the [[endothelial]] cells of barrier tissues such as the [[blood–brain barrier]].<ref>{{cite journal | vauthors = Uldry M, Thorens B | title = The SLC2 family of facilitated hexose and polyol transporters | journal = Pflügers Archiv | volume = 447 | issue = 5 | pages = 480–9 | date = February 2004 | pmid = 12750891 | doi = 10.1007/s00424-003-1085-0 | s2cid = 25539725 | url = http://doc.rero.ch/record/316469/files/424_2004_Article_1264.pdf }}</ref>
== Clinical significance ==
Mutations in the GLUT1 gene are responsible for GLUT1 deficiency or [[De Vivo disease]], which is a rare [[Dominance (genetics)|autosomal dominant]] disorder.<ref>{{cite journal | vauthors = Seidner G, Alvarez MG, Yeh JI, O'Driscoll KR, Klepper J, Stump TS, Wang D, Spinner NB, Birnbaum MJ, De Vivo DC | title = GLUT-1 deficiency syndrome caused by haploinsufficiency of the
=== GLUT1 Deficiency Syndrome 1 ===
Many mutations in the ''SLC2A1'' gene, including LYS456TER, TYR449TER, LYS256VAL, ARG126HIS, ARG126LEU and GLY91ASP, have been shown to cause GLUT1 deficiency syndrome 1 (GLUT1DS1), a [[Neurological disorder|neurologic disorder]] showing wide [[Phenotype|phenotypic]] variability. This disease can be inherited in either an [[
=== GLUT1 Deficiency Syndrome 2 ===
Other mutations, like GLY314SER, ALA275THR, ASN34ILE, SER95ILE, ARG93TRP, ARG91TRP, a 3-bp [[Insertion (genetics)|insertion]] (TYR292) and a 12-bp [[Deletion (genetics)|deletion]] (1022_1033del) in exon 6, have been shown to cause GLUT1 deficiency syndrome 2 (GLUT1DS2), a clinically variable disorder characterized primarily by onset in childhood of paroxysmal exercise-induced [[dyskinesia]]. The dyskinesia involves transient abnormal involuntary [[
=== Idiopathic Generalized Epilepsy 12 ===
Some mutations, particularly ASN411SER, ARG458TRP, ARG223PRO and ARG232CYS, have been shown to cause idiopathic generalized epilepsy 12 (EIG12), a disorder characterized by recurring generalized seizures in the absence of detectable [[brain]] [[lesion]]s and/or [[Metabolic disorder|metabolic abnormalities]]. Generalized seizures arise diffusely and simultaneously from both [[Cerebral hemisphere|hemispheres of the brain]]. Seizure types include [[
=== Dystonia 9 ===
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=== Stomatin-deficient Cryohydrocytosis ===
Certain mutations, like GLY286ASP and a 3-bp deletion in ILE435/436, cause [[Stomatin]]-deficient cryohydrocytosis with neurologic defects (SDCHCN), a rare form of stomatocytosis characterized by episodic [[hemolytic anemia]], cold-induced red cells [[Ion#
=== Role as a Receptor for HTLV ===
GLUT1 is also a receptor used by the [[Human T-lymphotropic virus|HTLV]] virus to gain entry into target cells.<ref>{{cite journal | vauthors = Manel N, Kim FJ, Kinet S, Taylor N, Sitbon M, Battini JL | title = The ubiquitous glucose transporter GLUT-1 is a receptor for HTLV | journal = Cell | volume = 115 | issue = 4 | pages = 449–59 | date = November 2003 | pmid = 14622599 | doi = 10.1016/S0092-8674(03)00881-X |
=== Role as a Histochemical Marker for Hemangioma ===
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== Interactions ==
GLUT1 has been shown to [[Protein-protein interaction|interact]] with [[GIPC1]].<ref name="pmid10198040">{{cite journal | vauthors = Bunn RC, Jensen MA, Reed BC | title = Protein interactions with the glucose transporter binding protein GLUT1CBP that provide a link between GLUT1 and the cytoskeleton | journal = Molecular Biology of the Cell | volume = 10 | issue = 4 | pages = 819–32 | date = April 1999 | pmid = 10198040 | pmc = 25204 | doi = 10.1091/mbc.10.4.819 }}</ref> It is found in a [[protein complex|complex]] with Adducin ([[ADD2]]) and Dematin ([[
GLUT1 has two significant types in the brain:
Recently
==Inhibitors==
Fasentin is a small molecule inhibitor of the intracellular domain of GLUT1 preventing glucose uptake.<ref name="pmid19001437">{{cite journal | vauthors = Wood TE, Dalili S, Simpson CD, Hurren R, Mao X, Saiz FS, Gronda M, Eberhard Y, Minden MD, Bilan PJ, Klip A, Batey RA, Schimmer AD | title = A novel inhibitor of glucose uptake sensitizes cells to FAS-induced cell death | journal = Molecular Cancer Therapeutics | volume = 7 | issue = 11 | pages = 3546–55 | date = November 2008 | pmid = 19001437 | doi = 10.1158/1535-7163.MCT-08-0569 | s2cid = 7706108 | url = http://mct.aacrjournals.org/cgi/pmidlookup?view=long&pmid=19001437 | doi-access = free }}</ref>
Recently, a new more selective GLUT1 inhibitor, Bay-876, has been described.<ref name="pmid27552707">{{cite journal |vauthors=Siebeneicher H, Cleve A, Rehwinkel H, Neuhaus R, Heisler I, Müller T, Bauser M, Buchmann B |title=Identification and Optimization of the First Highly Selective GLUT1 Inhibitor BAY-876 |journal=ChemMedChem |volume=7 |issue=11 |pages=3546–55 |date=October 2016 |pmid=27552707 |pmc=5095872 |doi=10.1002/cmdc.201600276 |doi-access=free}}</ref>
==Interactive pathway map==
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== References ==
{{reflist|
== Further reading ==
{{refbegin|
* {{cite journal | vauthors = Lankford J, Butler IJ, Koenig MK | title = Glucose transporter type I deficiency causing mitochondrial dysfunction | journal = Journal of Child Neurology | volume = 27 | issue = 6 | pages = 796–8 | date = June 2012 | pmid = 22156785 | doi = 10.1177/0883073811426503 | s2cid = 206549634 }}
* {{cite journal | vauthors = North PE, Waner M, Mizeracki A, Mihm MC | title = GLUT1: a newly discovered immunohistochemical marker for juvenile hemangiomas | journal = Human Pathology | volume = 31 | issue = 1 | pages = 11–22 | date = January 2000 | pmid = 10665907 | doi = 10.1016/S0046-8177(00)80192-6 }}
* {{cite journal | vauthors = Hruz PW, Mueckler MM | title = Structural analysis of the GLUT1 facilitative glucose transporter (review) | journal = Molecular Membrane Biology | volume = 18 | issue = 3 | pages = 183–93 | year = 2001 | pmid = 11681785 | doi = 10.1080/09687680110072140 | s2cid = 218897534 | doi-access = free }}
* {{cite journal | vauthors = Baumann MU, Deborde S, Illsley NP | title = Placental glucose transfer and fetal growth | journal = Endocrine | volume = 19 | issue = 1 | pages = 13–22 | date = October 2002 | pmid = 12583599 | doi = 10.1385/ENDO:19:1:13 | s2cid = 26301249 }}
* {{cite journal | vauthors = Mobasheri A, Richardson S, Mobasheri R, Shakibaei M, Hoyland JA | title = Hypoxia inducible factor-1 and facilitative glucose transporters GLUT1 and GLUT3: putative molecular components of the oxygen and glucose sensing apparatus in articular chondrocytes | journal = Histology and Histopathology | volume = 20 | issue = 4 | pages = 1327–38 | date = October 2005 | pmid = 16136514 | doi = 10.14670/HH-20.1327
{{refend}}
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*[https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=glut1 GeneReviews/NIH/UW entry on Glucose Transporter Type 1 Deficiency Syndrome]
* {{MeshName|Glucose+Transporter+Type+1}}
* {{PDBe-KB2|P11166|Solute carrier family 2, facilitated glucose transporter member 1}}
{{Solute carrier family|bg|bg0}}
{{NLM content}}
[[Category:Integral membrane proteins]]
[[Category:Solute carrier family]]
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