Monocarboxylate transporter 1 (SLC16A1)

The protein contains 500 amino acids for an estimated molecular weight of 53944 Da.

 

Proton-coupled monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate. Depending on the tissue and on cicumstances, mediates the import or export of lactic acid and ketone bodies. Required for normal nutrient assimilation, increase of white adipose tissue and body weight gain when on a high-fat diet. Plays a role in cellular responses to a high-fat diet by modulating the cellular levels of lactate and pyruvate, small molecules that contribute to the regulation of central metabolic pathways and insulin secretion, with concomitant effects on plasma insulin levels and blood glucose homeostasis. (updated: March 4, 2015)

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.
Protein sequence (FASTA)
Protein coevolution profile (FreeContact)
Multiple Sequence Alignment (Muscle)

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

Topcons

Interpro domains
Total structural coverage: 0%
Model score: 0
No model available.

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VariantDescription
dbSNP:rs11551867
SDLT
MCT1D
SDLT
dbSNP:rs1049434

The reference OMIM entry for this protein is 245340

Erythrocyte lactate transporter defect
Lactate transporter defect, myopathy due to

A number sign (#) is used with this entry because erythrocyte lactate transporter defect is caused by mutation in the SLC16A1 gene (600682).

CLINICAL FEATURES

Fishbein (1986) described the case of a 26-year-old military drill instructor in 'superb physical condition' who had experienced 3 brief episodes of severe, diffuse anterior chest pain after exercise during the previous 5 years. The chest pain was at first considered cardiac in origin; after further studies, it was attributed to the metabolic myopathy of chest wall musculature. Using a clinical assay for the human erythrocyte lactate transporter and an ischemic exercise test suitable for evaluating muscle lactate transport, Fishbein (1986) demonstrated a deficiency of lactate transporter in both striated muscles and red blood cells from the patient. As a result, an acidic intracellular environment was created by muscle activity with consequent degeneration of muscle and release of myoglobin and creatine kinase. Fishbein (1986) noted that there are a number of enzymes which, although not essential for muscular activity, are important perquisites for maximal performance. One of these is myoadenylate deaminase (AMPD1; 102770). Fishbein (1986) referred to these enzymes as 'perquisitory' catalysts and suggested that defects in such catalysts may be expected to produce 'diseases of healthy people.' Most patients whose major complaint is of muscle pain or weakness are never identified with a specific disease or pathologic diagnosis. Fishbein et al. (1988) developed a physiologic assay for the human erythrocyte lactate transporter. With this test, the authors identified 8 males, aged 14 to 56 years, in good general health but with elevated serum creatine kinase levels and evidence of lactate transporter defect. Two patients had episodes of rhabdomyolysis and myoglobinuria after exercise, 3 had bouts of muscle cramping on exercise, 2 had such bouts as well as progressive muscle stiffness over 5 to 7 years, and 1 had minimal symptoms. The deficiency of enzyme was partial (50-75% loss) in all cases. Fishbein (1989) suggested that such defects may be a common cause of metabolic myopathy, fitness-failure, and postexertional rhabdomyolysis. Merezhinskaya et al. (2000) reported 5 unrelated males with subnormal erythrocyte lactate transport and symptoms and signs of muscle injury on exercise and heat exposure. One of the patients had previously been reported by Fishbein (1986). Clinical features included muscle cramping or stiffness, increased serum creatine kinase, normal EMG, and normal muscle biopsies. One patient demonstrated delayed lactate decline in exercised muscle.

MOLECULAR GENETICS

In a patient with erythrocyte lactate transporter defect originally reported by Fishbein (1986), Merezhinskaya et al. (2000) identified a heterozygous mutation in the SLC16A1 gene (600682.0001). Two additional patients were found to be heterozygous for another SLC16A1 mutation (600682.0002). All 3 patients had erythrocyte lactate clearance rates that were 40 to 50% of normal control values. The authors suggested that homozygous individuals would be more severely compromised. ... More on the omim web site

Subscribe to this protein entry history

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

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

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 245340 was added.