1. Home
  2. Targets
  3. transporter
  4. Monocarboxylate transporter 5

Tbio Monocarboxylate transporter 5

Proton-linked 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 (By similarity).

 Comments

Property Summary

NCBI Gene PubMed Count 62
PubMed Score 1.41
PubTator Score 48.42

Knowledge Summary

Patent

No data available

TINX Plot

  Disease (2)

Disease Target Count Z-score Confidence
Pseudomyxoma peritonei 6 3.823 1.9

Expression

  Differential Expression (16)

Disease log2 FC p
malignant mesothelioma -1.700 3.4e-07
astrocytoma 1.100 6.4e-09
glioblastoma 1.800 1.4e-04
posterior fossa group A ependymoma 3.200 1.5e-15
group 4 medulloblastoma 3.100 3.2e-09
non-small cell lung cancer -1.696 3.9e-11
active Crohn's disease 1.366 1.3e-02
active ulcerative colitis 2.209 1.7e-02
pancreatic cancer 1.400 1.2e-03
interstitial cystitis 1.400 2.8e-03
adult high grade glioma 2.100 2.7e-04
pilocytic astrocytoma 1.900 4.3e-06
lung carcinoma -1.800 1.0e-17
Breast cancer -1.900 2.1e-06
ovarian cancer -1.900 4.0e-09
pituitary cancer -1.100 4.2e-07

Synonym

Accession O15374 A8K3V5 B2R9C9 B4DJ67 B4DPX7 E7EPY8 G3V175 Q5T612 Q8WU09 MCT 5
Symbols MCT4
MCT5

Gene

SLC16A4

PANTHER Protein Class (1)

  Ortholog (1)

Species Source Disease
Macaque OMA EggNOG Inparanoid

 UniProt Keyword (10)

 GO Function (3)

 GO Component (2)

 GO Process (2)

 Compartment GO Term (15)

 HCA RNA Cell Line (56)

See all...

Pathway (1)

Gene RIF (52)

PMID Text
26876179 MCT1 inhibition impairs proliferation of glycolytic breast cancer cells co-expressing MCT1 and MCT4 via disruption of pyruvate rather than lactate export.
26779534 MCT1 expression was not clearly associated with overall or disease-free survival. MCT4 and CD147 expression correlate with worse prognosis across many cancer types. These results warrant further investigation of these associations
26384346 Prognostic significance of CD147 protein expression could not surpass that of MCT4, especially of SLC16A3 DNA methylation, corroborating the role of MCT4 as prognostic biomarker for ccRCC.
26363456 Knockdown of MCT4 blocks lactate efflux to result in lactic acid accumulation and pH dropping, which is involved in triggering apoptosis in HUVECs.
26213210 synovial fibroblasts from patients with rheumatoid arthritis exhibited up-regulated transcription of MCT4 mRNA compared with osteoarthritis patients. Knockdown of MCT4 induced intrinsic apoptosis of fibroblasts, thereby inhibiting their proliferation.
26059436 we showed that genetic disruption of Mct4 and/or Ampk dramatically reduced tumourigenicity in a xenograft mouse model suggesting a crucial role for these two actors in establishment of tumours in a nutrient-deprived environment
25965974 MCT4 expression is regulated by the PI3K-Akt signalling pathway and highly expressed in HER2-positive breast cancers where it regulates tumor cell metabolism and survival.
25957999 The first IF method has been developed and optimised for detection of MCT 1 and MCT4 in cancer patient circulating tumour cells .
25919709 Findings demonstrate that the histidine residue His382 in the extracellular loop of the transporter is essential for pH regulation of MCT4-mediated substrate transport activity.
25578492 we sought to evaluate the associations of nine functional SNPs in genes encoding MCT1, MCT2, and MCT4 with the prognosis in a cohort of 500 Chinese NSCLC patients.
25446815 MCT4 expression can predict survival and trans-arterial chemoembolization treatment response for hepatocellular carcinoma patients. MCT4 plays a role in cell proliferation and migration/invasion.
25406319 MCT4 is up-regulated in inflammation-activated macrophages and required for innate immune response.
25374230 High monocarboxylate transporter 4 protein expression in stromal cells is associated with invasiveness in gastric cancer.
25058459 MCT4 demonstrated the strongest deleterious impact on survival in triple negative breast cancer patients.MCT4 should serve as a new prognostic factor in node-negative breast cancers.
24797797 These results indicate there are no additional benefits of IHT when compared to similar normoxic training. Hence, the addition of the hypoxic stimulus on anaerobic performance or MCT expression after a three-week training period is ineffective.
24498219 The critical role of MCT4 in cell proliferation.
24464262 Decreased astroglial monocarboxylate transporter 4 expression in temporal lobe epilepsy
24433439 Aberrant expression of MCT4 in carcinoma cells serves as a novel, independent prognostic factor for HCC, indicating a poorer patient outcome.
24338019 Coexpression of CAIV with MCT1 and MCT4 resulted in a significant increase in MCT transport activity.
24077291 MCT4 upregulation correlated with the aggressive mesenchymal subset of glioblastoma (GBM), and MCT4 downregulation correlated with the less aggressive G-CIMP (Glioma CpG Methylator Phenotype) subset of GBM.
23935841 Results suggest that Arginine-278 in transmembrane-spanning domains TMD8 is a critical residue involved in L-lactate recognition by monocarboxylate transporter 4 (hMCT4).
23907124 Alterations in Cav-1 and MCT4 expression may mark a critical point in the progression from in situ to invasive breast cancer.
23881922 Upregulation of MCT4 expression via SLC16A3 promoter DNA methylation is associated with clear cell renal cell carcinoma.
23780984 High MCT4 contributes to the growth of colorectal cancer with vascular endothelial growth factor.
23574725 MCT1 and MCT4 biomarkers were employed to determine the metabolic state of proliferative cancer cells.
23258846 Overexpression of MCT4 is associated with gliomas.
23187830 Combined application of GLUT-1, MCT-1, and MCT-4 immunohistochemistry might be useful in differentiating malignant pleural mesothelioma from reactive mesothelial hyperplasia.
22362593 Data suggest that MCT4 may serve as a novel metabolic target to reverse the Warburg effect and limit disease progression in renal cell carcinoma.
22240841 Report SNPs in MCT4 (SLC16A3) gene in the Chinese and Indian populations of Singapore.
22153830 High GLUT1 plus high MCT4 expression indicated an aggressive tumor behavior in adenocarcinomas.
21930917 CD147 subunit of lactate/H+ symporters MCT1 and hypoxia-inducible MCT4 is critical for energetics and growth of glycolytic tumors.
21870331 both MCT1 and CD147, but not MCT4, were associated with GLUT1 and CAIX expression in a large series of invasive breast carcinoma samples
21787388 Data show that a significant increase of MCT2 and MCT4 expression in the cytoplasm of tumour cells and a significant decrease in both MCT1 and CD147 expression in prostate tumour cells was observed when compared to normal tissue.
21558814 breast cancer cells specifically induce the expression of MCT4 in cancer-associated fibroblasts; the expression of MCT4 in cancer-associated fibroblasts is due to oxidative stress
21306479 We found that the expression of the monocarboxylate transporters MCT1 and MCT4, but not MCT5, in human lung cancer cell lines was significantly correlated with invasiveness
20658178 The result suggest that co-expression of CD147 and MCT1/MCT4 is related to drug resistance during EOC metastasis and could be useful therapeutic targets to prevent the development of incurable, recurrent and drug resistance EOC.
20454640 MCT1, MCT2, and MCT4 protein expression in breast, colon, lung, and ovary neoplasms, as well as CD147 and CD44, were analysed.
20035863 In corneal epithelium and cell lines human monocarboxylic acid transporter 4 is expressed at mRNA and protein levels.
19876643 Data suggest that hypoxia increases lactate release from adipocytes and modulates MCT expression in a type-specific manner, with MCT1 and MCT4, but not MCT2 expression, being hypoxia-inducible transcription factor-1 (HIF-1) dependent.
19073896 Suggest that the specific interaction of MCT4 with beta(1)-integrin may regulate cell migration through modulation of focal adhesions.
18832090 Report effects of high-intensity training on muscle MCT1/4 and postexercise recovery of muscle lactate and hydrogen ions in women.
18635880 MCT4 was reduced by 35% in vastus lateralis in chronic obstructive pulmonary disease.
18188595 Expression of MCT1 and MCT4 showed a significant gain in plasma membranes of colorectal neoplasms.
18079261 Elevated muscle MCT4 in obesity could reflect the need to release greater amounts of muscle lactate. Weight loss decreased MCT4.
18056982 an exercise protocol designed to strain muscle carbohydrate reserves and to result in large increases in lactic acid results in a rapid upregulation of both GLUT-4 and MCT-4
17082373 A single bout of high-intensity exercise decreased both MCT relative abundance (MCT1 and MCT4) in membrane preparations.
16452478 MCT4, like other glycolytic enzymes, is up-regulated by hypoxia through a HIF-1alpha-mediated mechanism
16408234 this study shows conflicting adaptations in MCT1 and MCT4 protein and mRNA levels following training, which may indicate post-transcriptional regulation of MCT expression in human muscle.
16403666 Expressed in leukocytes and platelets; truncated 32kdal form may have a physiological function.
15917240 inhibition of MCT1 and MCT4 activity by pCMBS is mediated through its binding to CD147, acting as an ancillary protein required to maintain the catalytic activity of MCTs 1 and 4, as well as for their translocation to the plasma membrane
15135232 studies demonstrate that the opposing plasma membranes of human syncytiotrophoblast are polarized with respect to both monocarboxylate transporter MCT1 and MCT4 activity and expression
14724187 MCT1 was lower and MCT4 similar in Type 2 diabetes versus control. With training, MCT1 content always increased, while MCT4 only increased in control.

AA Sequence 

MLKREGKVQPYTKTLDGGWGWMIVIHFFLVNVFVMGMTKTFAIFFVVFQEEFEGTSEQIGWIGSIMSSLR      1 - 70
FCAGPLVAIICDILGEKTTSILGAFVVTGGYLISSWATSIPFLCVTMGLLPGLGSAFLYQVAAVVTTKYF     71 - 140
KKRLALSTAIARSGMGLTFLLAPFTKFLIDLYDWTGALILFGAIALNLVPSSMLLRPIHIKSENNSGIKD    141 - 210
KGSSLSAHGPEAHATETHCHETEESTIKDSTTQKAGLPSKNLTVSQNQSEEFYNGPNRNRLLLKSDEESD    211 - 280
KVISWSCKQLFDISLFRNPFFYIFTWSFLLSQLAYFIPTFHLVARAKTLGIDIMDASYLVSVAGILETVS    281 - 350
QIISGWVADQNWIKKYHYHKSYLILCGITNLLAPLATTFPLLMTYTICFAIFAGGYLALILPVLVDLCRN    351 - 420
STVNRFLGLASFFAGMAVLSGPPIAGWLYDYTQTYNGSFYFSGICYLLSSVSFFFVPLAERWKNSLT       421 - 487
//

Text Mined References (64)

PMID Year Title
26876179 2016 MCT1 Modulates Cancer Cell Pyruvate Export and Growth of Tumors that Co-express MCT1 and MCT4.
26779534 2015 Prognostic Indications of Elevated MCT4 and CD147 across Cancer Types: A Meta-Analysis.
26384346 2015 MCT4 surpasses the prognostic relevance of the ancillary protein CD147 in clear cell renal cell carcinoma.
26363456 2015 High glucose and interleukin 1?-induced apoptosis in human umbilical vein endothelial cells involves in down-regulation of monocarboxylate transporter 4.
26213210 2015 Monocarboxylate transporter 4, associated with the acidification of synovial fluid, is a novel therapeutic target for inflammatory arthritis.
26059436 2015 AMP-activated protein kinase is dispensable for maintaining ATP levels and for survival following inhibition of glycolysis, but promotes tumour engraftment of Ras-transformed fibroblasts.
25965974 2015 Functional screening identifies MCT4 as a key regulator of breast cancer cell metabolism and survival.
25957999 2015 Optimisation of immunofluorescence methods to determine MCT1 and MCT4 expression in circulating tumour cells.
25919709 2014 Involvement of Histidine Residue His382 in pH Regulation of MCT4 Activity.
25578492 2015 Genetic variations in monocarboxylate transporter genes as predictors of clinical outcomes in non-small cell lung cancer.
25446815 2015 Monocarboxylate transporter 4 predicts poor prognosis in hepatocellular carcinoma and is associated with cell proliferation and migration.
25406319 2015 The monocarboxylate transporter 4 is required for glycolytic reprogramming and inflammatory response in macrophages.
25374230 2014 High monocarboxylate transporter 4 protein expression in stromal cells predicts adverse survival in gastric cancer.
25058459 2014 Expression of the hypoxia-inducible monocarboxylate transporter MCT4 is increased in triple negative breast cancer and correlates independently with clinical outcome.
24797797 2014 Effects of intermittent training on anaerobic performance and MCT transporters in athletes.
24498219 2014 Monocarboxylate transporter 4 facilitates cell proliferation and migration and is associated with poor prognosis in oral squamous cell carcinoma patients.
24464262 2014 Decreased astroglial monocarboxylate transporter 4 expression in temporal lobe epilepsy.
24433439 2014 Aberrant expression of monocarboxylate transporter 4 in tumour cells predicts an unfavourable outcome in patients with hepatocellular carcinoma.
24338019 2014 Intracellular and extracellular carbonic anhydrases cooperate non-enzymatically to enhance activity of monocarboxylate transporters.
24077291 2014 Inhibition of monocarboxylate transporter-4 depletes stem-like glioblastoma cells and inhibits HIF transcriptional response in a lactate-independent manner.
23935841 2013 Crucial residue involved in L-lactate recognition by human monocarboxylate transporter 4 (hMCT4).
23907124 2013 Loss of caveolin-1 and gain of MCT4 expression in the tumor stroma: key events in the progression from an in situ to an invasive breast carcinoma.
23881922 2013 DNA methylation of the SLC16A3 promoter regulates expression of the human lactate transporter MCT4 in renal cancer with consequences for clinical outcome.
23780984 2013 Expression of monocarboxylate transporter (MCT)-4 in colorectal cancer and its role: MCT4 contributes to the growth of colorectal cancer with vascular endothelial growth factor.
23574725 2013 Cancer metabolism, stemness and tumor recurrence: MCT1 and MCT4 are functional biomarkers of metabolic symbiosis in head and neck cancer.
23258846 2013 Monocarboxylate transporters (MCTs) in gliomas: expression and exploitation as therapeutic targets.
23187830 2013 Expression and role of GLUT-1, MCT-1, and MCT-4 in malignant pleural mesothelioma.
22362593 2012 Genome-wide RNA interference analysis of renal carcinoma survival regulators identifies MCT4 as a Warburg effect metabolic target.
22240841 2012 Genetic variations of the MCT4 (SLC16A3) gene in the Chinese and Indian populations of Singapore.
22153830 2012 Differences in metabolism between adeno- and squamous cell non-small cell lung carcinomas: spatial distribution and prognostic value of GLUT1 and MCT4.
21930917 2011 CD147 subunit of lactate/H+ symporters MCT1 and hypoxia-inducible MCT4 is critical for energetics and growth of glycolytic tumors.
21870331 2011 GLUT1 and CAIX expression profiles in breast cancer correlate with adverse prognostic factors and MCT1 overexpression.
21787388 2011 Monocarboxylate transporter 4 (MCT4) and CD147 overexpression is associated with poor prognosis in prostate cancer.
21558814 2011 Evidence for a stromal-epithelial "lactate shuttle" in human tumors: MCT4 is a marker of oxidative stress in cancer-associated fibroblasts.
21306479 2011 Monocarboxylate transporters 1 and 4 are involved in the invasion activity of human lung cancer cells.
20658178 2010 Co-expression of CD147/EMMPRIN with monocarboxylate transporters and multiple drug resistance proteins is associated with epithelial ovarian cancer progression.
20454640 2010 Expression of monocarboxylate transporters 1, 2, and 4 in human tumours and their association with CD147 and CD44.
20035863 2010 Monocarboxylate transport in human corneal epithelium and cell lines.
19876643 2010 Hypoxia stimulates lactate release and modulates monocarboxylate transporter (MCT1, MCT2, and MCT4) expression in human adipocytes.
19073896 2009 Interaction of monocarboxylate transporter 4 with beta1-integrin and its role in cell migration.
18832090 2008 Effects of high-intensity training on muscle lactate transporters and postexercise recovery of muscle lactate and hydrogen ions in women.
18635880 2008 Altered metabolic and transporter characteristics of vastus lateralis in chronic obstructive pulmonary disease.
18188595 2008 Increased expression of monocarboxylate transporters 1, 2, and 4 in colorectal carcinomas.
18079261 2008 Effect of weight loss on lactate transporter expression in skeletal muscle of obese subjects.
18056982 2008 Rapid upregulation of GLUT-4 and MCT-4 expression during 16 h of heavy intermittent cycle exercise.
17082373 2007 High-intensity exercise acutely decreases the membrane content of MCT1 and MCT4 and buffer capacity in human skeletal muscle.
16710414 2006 The DNA sequence and biological annotation of human chromosome 1.
16452478 2006 The plasma membrane lactate transporter MCT4, but not MCT1, is up-regulated by hypoxia through a HIF-1alpha-dependent mechanism.
16408234 2006 The effects of short-term sprint training on MCT expression in moderately endurance-trained runners.
16403666 2006 Expression of monocarboxylate transporter 4 in human platelets, leukocytes, and tissues assessed by antibodies raised against terminal versus pre-terminal peptides.
15917240 2005 Basigin (CD147) is the target for organomercurial inhibition of monocarboxylate transporter isoforms 1 and 4: the ancillary protein for the insensitive MCT2 is EMBIGIN (gp70).
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15342556 2004 Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions.
15135232 2004 Polarized lactate transporter activity and expression in the syncytiotrophoblast of the term human placenta.
14724187 2004 Effects of strength training on muscle lactate release and MCT1 and MCT4 content in healthy and type 2 diabetic humans.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
12739169 2004 The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond.
12657613 2003 Polarized expression of monocarboxylate transporters in human retinal pigment epithelium and ARPE-19 cells.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
11101640 2000 Characterisation of human monocarboxylate transporter 4 substantiates its role in lactic acid efflux from skeletal muscle.
10510291 1999 The proton-linked monocarboxylate transporter (MCT) family: structure, function and regulation.
10329977 1999 Distribution of the lactate/H+ transporter isoforms MCT1 and MCT4 in human skeletal muscle.
9425115 1998 Cloning and sequencing of four new mammalian monocarboxylate transporter (MCT) homologues confirms the existence of a transporter family with an ancient past.
8125298 1994 Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.