Solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1)

The protein contains 492 amino acids for an estimated molecular weight of 54084 Da.

 

Facilitative glucose transporter, which is responsible for constitutive or basal glucose uptake (PubMed:18245775, PubMed:19449892, PubMed:25982116, PubMed:27078104, PubMed:10227690). Has a very broad substrate specificity; can transport a wide range of aldoses including both pentoses and hexoses (PubMed:18245775, PubMed:19449892). Most important energy carrier of the brain: present at the blood-brain barrier and assures the energy-independent, facilitative transport of glucose into the brain (PubMed:10227690). In association with BSG and NXNL1, promotes retinal cone survival by increasing glucose uptake into photoreceptors (By similarity). (updated: Oct. 7, 2020)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
  6. D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
  7. Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

This protein is annotated as membranous in Gene Ontology, is annotated as membranous in UniProt, is predicted to be membranous by TOPCONS.


Interpro domains
Total structural coverage: 100%
Model score: 90

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VariantDescription
GLUT1DS2
GLUT1DS1
GLUT1DS1
GLUT1DS1
GLUT1DS1
GLUT1DS2
GLUT1DS2
GLUT1DS2
GLUT1DS1
GLUT1DS1, GLUT1DS2 and DYT9
GLUT1DS1
GLUT1DS1
GLUT1DS1
GLUT1DS1
GLUT1DS1; 44% of wild-type glucose uptake activity
GLUT1DS2
GLUT1DS1
GLUT1DS2
GLUT1DS1 and DYT9
GLUT1DS1
EIG12
GLUT1DS1
EIG12
GLUT1DS1
GLUT1DS2
GLUT1DS2
GLUT1DS1
Found in a patient with GLUT1 deficiency syndrome
GLUT1DS1
GLUT1DS2
GLUT1DS2
GLUT1DS2
GLUT1DS1; stabilizes the inward-open conformation
GLUT1DS1 and GLUT1DS2
GLUT1DS1
GLUT1DS1
GLUT1DS1
GLUT1DS1
GLUT1DS1; creates a dileucine internalization motif that promotes recruitment of clathrin and mislocalization of the protein to endocytic compartments
EIG12
EIG12
EIG12
EIG12; unknown pathological significance
EIG12; decreased glucose transport
EIG12
EIG12; decreased glucose transport
SDCHCN
EIG12
EIG12

The reference OMIM entry for this protein is 138140

Solute carrier family 2 (facilitated glucose transporter), member 1; slc2a1
Glucose transporter 1; glut; glut1
Erythrocyte/hepatoma glucose transporter

DESCRIPTION

The GLUT1 (HepG2) gene encodes the major glucose transporter in brain, placenta, and erythrocytes (Baroni et al., 1992).

CLONING

Mueckler et al. (1985) isolated a cDNA corresponding to human GLUT1 from human HepG2 hepatoma cells. The deduced amino acid sequence indicates that this protein lacks a signal sequence and possesses 12 potential membrane-spanning domains. The amino terminus, carboxyl terminus, and a highly hydrophilic domain in the center of the protein ware all predicted to lie on the cytoplasmic face of the cell. Wang et al. (2000) stated that the SLC2A1 gene encodes a 492-amino acid protein with 97 to 98% identity between human, rat, rabbit, and pig sequences.

GENE STRUCTURE

Wang et al. (2000) stated the SLC2A1 gene contains 10 exons and spans approximately 35 kb.

BIOCHEMICAL FEATURES

- Crystal Structure Deng et al. (2014) reported the crystal structure of human GLUT1 at 3.2-angstrom resolution. The full-length protein, which has a canonical major facilitator superfamily fold, is captured in an inward-open conformation. This structure allows accurate mapping and potential mechanistic interpretation of disease-associated mutations in GLUT1. Structure-based analysis of these mutations provides insight into the alternating access mechanism of GLUT1 and other members of the sugar porter subfamily. Structural comparison of the uniporter GLUT1 with its bacterial homolog XylE, a proton-coupled xylose symporter, allows examination of the transport mechanisms of both passive facilitators and active transporters.

MAPPING

Wang et al. (2005) stated that the SLC2A1 gene maps to chromosome 1p34.2. Shows et al. (1987) mapped the SLC2A1 gene to chromosome 1p35-p31.3 by in situ hybridization and by Southern blot analysis of somatic cell hybrids. They concluded that the most likely location of SLC2A1 is in 1p33. Ardinger et al. (1987) found linkage between Rh and a DNA polymorphism for GLUT (theta = 0.21; lod = 3.54). Multipoint analysis indicated that the order of the loci is probably RH--3--ALPL--12--GLUT--23--PGM1, with the interlocus intervals as percent recombination in males (female rate about 2.8 times the male rate). Xiang et al. (1987) described a RFLP of the GLUT locus.

GENE FUNCTION

The high metabolic requirements of the mammalian central nervous system require specialized structures for the facilitated transport of nutrients across the blood-brain barrier. The facilitative glucose transporter GLUT1 is expressed on endothelial cells at the blood-brain barrier and is responsible for glucose entry into the brain (Agus et al., 1997). Stereo-specific high-capacity carriers, including those that recognize glucose, are key components of this barrier, which also protects the brain against noxious substances. Agus et al. (1997) provided evidence that GLUT1 also transports dehydroascorbic acid (the oxidized form of vitamin C) into the brain. Vitamin C concentrations in the brain exceed those in blood by 10 fold. In both tissues, the vitamin is present primarily in the reduced form, ascorbic acid. Agus et al. (1997) showed that ascorbic acid is not able to cross the blood-brain barrier; in contrast, dehydroascorbic acid readily enters the brain and is retained in the brain tissue in the form of ascorbic acid. Transport of dehydroascorbic acid into the brain is inhibited by D-glucose, but not by L-glucose. Thus, transport of dehydroascorbic acid by GLUT1 is a mecha ... More on the omim web site

Subscribe to this protein entry history

Oct. 20, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.

July 4, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

May 12, 2019: Protein entry updated
Automatic update: comparative model for a membrane protein was added.

May 12, 2019: Protein entry updated
Automatic update: model status changed

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 138140 was added.

Jan. 28, 2016: Protein entry updated
Automatic update: model status changed

Jan. 25, 2016: Protein entry updated
Automatic update: model status changed