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Reviewed, UniProtKB/Swiss-Prot P11166 (GTR1_HUMAN)

Last modified February 9, 2010. Version 131. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Solute carrier family 2, facilitated glucose transporter member 1
Alternative name(s):
    Glucose transporter type 1, erythrocyte/brain
      Short name=GLUT-1
    HepG2 glucose transporter
Gene names
Name: SLC2A1
Synonyms: GLUT1
OrganismHomo sapiens (Human) [Complete proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length492 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level.

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General annotation (Comments)

Function

Facilitative glucose transporter. This isoform may be responsible for constitutive or basal glucose uptake. Has a very broad substrate specificity; can transport a wide range of aldoses including both pentoses and hexoses.

Subcellular location

Cell membrane; Multi-pass membrane protein By similarity. Melanosome. Note: Localizes primarily at the cell surface By similarity. Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Ref.7

Tissue specificity

Expressed at variable levels in many human tissues.

Post-translational modification

Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.8

Involvement in disease

Defects in SLC2A1 are the cause of autosomal dominant GLUT1 deficiency syndrome [MIM:606777]; also known as blood-brain barrier glucose transport defect. This disease causes a defect in glucose transport across the blood-brain barrier. It is characterized by infantile seizures, delayed development, and acquired microcephaly.

Defects in SLC2A1 are the cause of dystonia type 18 (DYT18) [MIM:612126]. DYT18 is an exercise-induced paroxysmal dystonia/dyskinesia. Dystonia is defined by the presence of sustained involuntary muscle contraction, often leading to abnormal postures. DYT18 is characterized by attacks of involuntary movements triggered by certain stimuli such as sudden movement or prolonged exercise. In some patients involuntary exertion-induced dystonic, choreoathetotic, and ballistic movements may be associated with macrocytic hemolytic anemia. Ref.18

Sequence similarities

Belongs to the major facilitator superfamily. Sugar transporter (TC 2.A.1.1) family. Glucose transporter subfamily. [View classification]

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Ontologies

Keywords
   Biological processSugar transport
Transport
   Cellular componentCell membrane
Membrane
   DiseaseDisease mutation
Dystonia
   DomainTransmembrane
   PTMGlycoprotein
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Gene Ontology (GO)
   Biological processglucose transport

Traceable author statement. Source: ProtInc

transmembrane transport

Inferred from electronic annotation. Source: InterPro

   Cellular componentintegral to membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

melanosome

Inferred from electronic annotation. Source: UniProtKB-SubCell

membrane fraction

Traceable author statement. Source: ProtInc

Complete GO annotation...

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 492492Solute carrier family 2, facilitated glucose transporter member 1
PRO_0000050338

Regions

Topological domain1 – 1212Cytoplasmic Potential
Transmembrane13 – 33211 Potential
Topological domain34 – 6633Extracellular Potential
Transmembrane67 – 87212 Potential
Topological domain88 – 958Cytoplasmic Potential
Transmembrane96 – 116213 Potential
Topological domain117 – 12610Extracellular Potential
Transmembrane127 – 147214 Potential
Topological domain148 – 1558Cytoplasmic Potential
Transmembrane156 – 176215 Potential
Topological domain177 – 1859Extracellular Potential
Transmembrane186 – 206216 Potential
Topological domain207 – 27165Cytoplasmic Potential
Transmembrane272 – 292217 Potential
Topological domain293 – 30715Extracellular Potential
Transmembrane308 – 328218 Potential
Topological domain329 – 3379Cytoplasmic Potential
Transmembrane338 – 358219 Potential
Topological domain359 – 37113Extracellular Potential
Transmembrane372 – 3922110 Potential
Topological domain393 – 4019Cytoplasmic Potential
Transmembrane402 – 4222111 Potential
Topological domain423 – 4297Extracellular Potential
Transmembrane430 – 4502112 Potential
Topological domain451 – 49242Cytoplasmic Potential
Region279 – 2813Defines substrate specificity By similarity

Sites

Site4111Not glycosylated

Amino acid modifications

Modified residue2341Phosphothreonine By similarity
Modified residue4901Phosphoserine Ref.8
Glycosylation451N-linked (GlcNAc...) Ref.1 Ref.9

Natural variations

Natural variant341N → I in GLUT1 deficiency. Ref.16
VAR_054755
Natural variant341N → S in GLUT1 deficiency; 55% of wild-type glucose uptake activity. Ref.17
VAR_054756
Natural variant661S → F in GLUT1 deficiency. Ref.11
VAR_013283
Natural variant911G → D in GLUT1 deficiency; significantly decreases the transport of 3-O-methyl-D-glucose. Ref.14
VAR_013182
Natural variant1261R → C in GLUT1 deficiency. Ref.15
VAR_054757
Natural variant1261R → H in GLUT1 deficiency; significantly decreases the transport of 3-O-methyl-D-glucose and dehydroascorbic acid; 57% of wild-type glucose uptake activity. Ref.17 Ref.15 Ref.13
VAR_013183
Natural variant1261R → L in GLUT1 deficiency; compound heterozygote with V-256. Ref.11
VAR_013184
Natural variant1301G → S in GLUT1 deficiency; 75% of wild-type glucose uptake activity. Ref.17
VAR_054758
Natural variant1461E → K in GLUT1 deficiency. Ref.11 Ref.15
VAR_013284
Natural variant1531R → C in GLUT1 deficiency; 44% of wild-type glucose uptake activity. Ref.17 Ref.15
VAR_054759
Natural variant1691Missing in GLUT1 deficiency; 48% of wild-type glucose uptake activity.
VAR_054760
Natural variant2561K → E in GLUT1 deficiency; compound heterozygote with L-126. Ref.11
VAR_013185
Natural variant2751A → T in DYT18; the mutation decreases glucose transport but does not affect cation permeability. Ref.18
VAR_054761
Natural variant282 – 2854Missing in DYT18; accompanied by hemolytic anemia and altered erythrocyte ion concentrations; the mutation decreases glucose transport and causes a cation leak that alteres intracellular concentrations of sodium potassium and calcium.
VAR_054762
Natural variant2951T → M in GLUT1 deficiency; 75% of wild-type glucose uptake activity. Ref.17
VAR_054763
Natural variant3101T → I in GLUT1 deficiency. Ref.10
VAR_013285
Natural variant3141G → S in DYT18; the mutation decreases glucose transport but does not affect cation permeability. Ref.18
VAR_054764
Natural variant3331R → W in GLUT1 deficiency; 43% of wild-type glucose uptake activity. Ref.17 Ref.11 Ref.15
VAR_013286

Experimental info

Sequence conflict1521L → F in AAA52571. Ref.1

Secondary structure

1 ............................................................ 492
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
P11166-1 [UniParc].

Last modified October 3, 2006. Version 2.
Checksum: E71E1C6BD1B00B1E

FASTA49254,084
        10         20         30         40         50         60 
MEPSSKKLTG RLMLAVGGAV LGSLQFGYNT GVINAPQKVI EEFYNQTWVH RYGESILPTT 

        70         80         90        100        110        120 
LTTLWSLSVA IFSVGGMIGS FSVGLFVNRF GRRNSMLMMN LLAFVSAVLM GFSKLGKSFE 

       130        140        150        160        170        180 
MLILGRFIIG VYCGLTTGFV PMYVGEVSPT ALRGALGTLH QLGIVVGILI AQVFGLDSIM 

       190        200        210        220        230        240 
GNKDLWPLLL SIIFIPALLQ CIVLPFCPES PRFLLINRNE ENRAKSVLKK LRGTADVTHD 

       250        260        270        280        290        300 
LQEMKEESRQ MMREKKVTIL ELFRSPAYRQ PILIAVVLQL SQQLSGINAV FYYSTSIFEK 

       310        320        330        340        350        360 
AGVQQPVYAT IGSGIVNTAF TVVSLFVVER AGRRTLHLIG LAGMAGCAIL MTIALALLEQ 

       370        380        390        400        410        420 
LPWMSYLSIV AIFGFVAFFE VGPGPIPWFI VAELFSQGPR PAAIAVAGFS NWTSNFIVGM 

       430        440        450        460        470        480 
CFQYVEQLCG PYVFIIFTVL LVLFFIFTYF KVPETKGRTF DEIASGFRQG GASQSDKTPE 

       490 
ELFHPLGADS QV

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References

« Hide 'large scale' references
[1]"Sequence and structure of a human glucose transporter."
Mueckler M., Caruso C., Baldwin S.A., Panico M., Blench I., Morris H.R., Allard W.J., Lienhard G.E., Lodish H.F.
Science 229:941-945(1985) [PubMed: 3839598] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE, GLYCOSYLATION AT ASN-45, LACK OF GLYCOSYLATION AT ASN-411, MASS SPECTROMETRY.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[4]"Characterization and expression of human HepG2/erythrocyte glucose-transporter gene."
Fukumoto H., Seino S., Imura H., Seino Y., Bell G.I.
Diabetes 37:657-661(1988) [PubMed: 2834252] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-6.
[5]Yu W., Gibbs R.A.
Submitted (JUN-1998) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 150-492.
Tissue: Brain.
[6]"Molecular characterization and cloning of glucose transporters in human articular chondrocytes."
Neama G., Richardson S., Bell S., Carter S., Mobasheri A.
Submitted (MAY-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 294-423.
Tissue: Articular cartilage.
[7]"Proteomic and bioinformatic characterization of the biogenesis and function of melanosomes."
Chi A., Valencia J.C., Hu Z.-Z., Watabe H., Yamaguchi H., Mangini N.J., Huang H., Canfield V.A., Cheng K.C., Yang F., Abe R., Yamagishi S., Shabanowitz J., Hearing V.J., Wu C., Appella E., Hunt D.F.
J. Proteome Res. 5:3135-3144(2006) [PubMed: 17081065] [Abstract]
Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[8]"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.
Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-490, MASS SPECTROMETRY.
[9]"Mass-spectrometric identification and relative quantification of N-linked cell surface glycoproteins."
Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., Schiess R., Aebersold R., Watts J.D.
Nat. Biotechnol. 27:378-386(2009) [PubMed: 19349973] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-45, MASS SPECTROMETRY.
[10]"Defective glucose transport across brain tissue barriers: a newly recognized neurological syndrome."
Klepper J., Wang D., Fischbarg J., Vera J.C., Jarjour I.T., O'Driscoll K.R., De Vivo D.C.
Neurochem. Res. 24:587-594(1999) [PubMed: 10227690] [Abstract]
Cited for: VARIANT GLUT1 DEFICIENCY ILE-310.
[11]"Mutational analysis of GLUT1 (SLC2A1) in Glut-1 deficiency syndrome."
Wang D., Kranz-Eble P., De Vivo D.C.
Hum. Mutat. 16:224-231(2000) [PubMed: 10980529] [Abstract]
Cited for: VARIANTS GLUT1 DEFICIENCY PHE-66; LEU-126; LYS-146; GLU-256 AND TRP-333.
[12]Erratum
Wang D., Kranz-Eble P., De Vivo D.C.
Hum. Mutat. 16:527-527(2000)
[13]"Autosomal dominant Glut-1 deficiency syndrome and familial epilepsy."
Brockmann K., Wang D., Korenke C.G., von Moers A., Ho Y.-Y., Pascual J.M., Kuang K., Yang H., Ma L., Kranz-Eble P., Fischbarg J., Hanefeld F., De Vivo D.C.
Ann. Neurol. 50:476-485(2001) [PubMed: 11603379] [Abstract]
Cited for: VARIANT GLUT1 DEFICIENCY HIS-126.
[14]"Autosomal dominant transmission of GLUT1 deficiency."
Klepper J., Willemsen M., Verrips A., Guertsen E., Herrmann R., Kutzick C., Floercken A., Voit T.
Hum. Mol. Genet. 10:63-68(2001) [PubMed: 11136715] [Abstract]
Cited for: VARIANT GLUT1 DEFICIENCY ASP-91.
[15]"Imaging the metabolic footprint of Glut1 deficiency on the brain."
Pascual J.M., van Heertum R.L., Wang D., Engelstad K., De Vivo D.C.
Ann. Neurol. 52:458-464(2002) [PubMed: 12325075] [Abstract]
Cited for: VARIANTS GLUT1 DEFICIENCY HIS-126; CYS-126; LYS-146; CYS-153 AND TRP-333.
[16]"GLUT-1 deficiency without epilepsy -- an exceptional case."
Overweg-Plandsoen W.C.G., Groener J.E.M., Wang D., Onkenhout W., Brouwer O.F., Bakker H.D., De Vivo D.C.
J. Inherit. Metab. Dis. 26:559-563(2003) [PubMed: 14605501] [Abstract]
Cited for: VARIANT GLUT1 DEFICIENCY ILE-34.
[17]"Glut-1 deficiency syndrome: clinical, genetic, and therapeutic aspects."
Wang D., Pascual J.M., Yang H., Engelstad K., Jhung S., Sun R.P., De Vivo D.C.
Ann. Neurol. 57:111-118(2005) [PubMed: 15622525] [Abstract]
Cited for: VARIANTS GLUT1 DEFICIENCY SER-34; HIS-126; SER-130; CYS-153; LEU-169 DEL; MET-295 AND TRP-333, CHARACTERIZATION OF VARIANTS GLUT1 DEFICIENCY SER-34; HIS-126; SER-130; CYS-153; LEU-169 DEL; MET-295 AND TRP-333.
[18]"GLUT1 mutations are a cause of paroxysmal exertion-induced dyskinesias and induce hemolytic anemia by a cation leak."
Weber Y.G., Storch A., Wuttke T.V., Brockmann K., Kempfle J., Maljevic S., Margari L., Kamm C., Schneider S.A., Huber S.M., Pekrun A., Roebling R., Seebohm G., Koka S., Lang C., Kraft E., Blazevic D., Salvo-Vargas A. expand/collapse author list , Fauler M., Mottaghy F.M., Muenchau A., Edwards M.J., Presicci A., Margari F., Gasser T., Lang F., Bhatia K.P., Lehmann-Horn F., Lerche H.
J. Clin. Invest. 118:2157-2168(2008) [PubMed: 18451999] [Abstract]
Cited for: VARIANTS DYT18 THR-275; 282-GLN--SER-285 DEL AND SER-314.
+Additional computationally mapped references.

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Web resources

GeneReviews
Wikipedia

GLUT1 entry

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Cross-references

Sequence databases

EMBL
GenBank
DDBJ		K03195 mRNA. Translation: AAA52571.1.
AK312403 mRNA. Translation: BAG35317.1.
BC118590 mRNA. Translation: AAI18591.1.
M20653 Genomic DNA. Translation: AAB61084.1.
AF070544 mRNA. Translation: AAC28635.1.
AY034633 mRNA. Translation: AAK56795.1.
IPIIPI00220194.
PIRA27217.
RefSeqNP_006507.2.
UniGeneHs.473721

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1SUKmodel-A1-492[»]
SMRP11166. Positions 65-173, 66-456.
ModBaseSearch...

Protein-protein interaction databases

DIPDIP-23N.
IntActP11166. 1 interaction.
STRINGP11166.

Protein family/group databases

TCDB2.A.1.1.28. major facilitator superfamily (MFS).

PTM databases

GlycoSuiteDBP11166.
PhosphoSiteP11166.

Proteomic databases

PeptideAtlasP11166.
PRIDEP11166.

Genome annotation databases

EnsemblENST00000426263; ENSP00000416293; ENSG00000117394; Homo sapiens. [Genome view]
GeneID6513.
KEGGhsa:6513.
UCSCuc001cik.2. human.

Organism-specific databases

CTD6513.
GeneCardsGC01M043164.
H-InvDBHIX0023534.
HGNCHGNC:11005. SLC2A1.
HPACAB002759.
MIM138140. gene.
606777. phenotype.
612126. phenotype.
Orphanet98811. Dyskinesia, paroxysmal exertion-induced.
71277. Encephalopathy due to GLUT1 deficiency.
PharmGKBPA35875.
GenAtlasSearch...

Phylogenomic databases

eggNOGprNOG04801.
HOVERGENP11166.
OrthoDBEOG97DD24.
PhylomeDBP11166.

Enzyme and pathway databases

Pathway_Interaction_DBhif1_tfpathway. HIF-1-alpha transcription factor network.
ReactomeREACT_11193. Metabolism of vitamins and cofactors.
REACT_15518. Transmembrane transport of small molecules.
REACT_474. Metabolism of carbohydrates.

Gene expression databases

ArrayExpressP11166.
BgeeP11166.
CleanExHS_SLC2A1.
GenevestigatorP11166.
GermOnlineENSG00000117394. Homo sapiens.

Family and domain databases

InterProIPR002439. Glu_transpt_1.
IPR016196. MFS_general_subst_transpt.
IPR003663. Sugar/inositol_transpt.
IPR005829. Sugar_transporter_CS.
[Graphical view]
PRINTSPR01190. GLUCTRSPORT1.
PR00171. SUGRTRNSPORT.
TIGRFAMsTIGR00879. SP. 1 hit.
PROSITEPS50850. MFS. 1 hit.
PS00216. SUGAR_TRANSPORT_1. 1 hit.
PS00217. SUGAR_TRANSPORT_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

DrugBankDB00292. Etomidate.
NextBio25327.
SOURCESearch...

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Entry information

Entry nameGTR1_HUMAN
AccessionPrimary (citable) accession number: P11166
Secondary accession number(s): B2R620, O75535, Q147X2
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: October 3, 2006
Last modified: February 9, 2010
This is version 131 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

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SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents