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SLC16A3 (solute carrier family 16, member 3 (monocarboxylic acid transporter 4))

Written2010-03Céline Pinheiro, Fátima Baltazar
Life, Health Sciences Research Institute (ICVS), School of Health Sciences, University of Minho, Campus of Gualtar, 4710-057 Braga, Portugal

(Note : for Links provided by Atlas : click)

Identity

Alias_namessolute carrier family 16 (monocarboxylic acid transporters), member 3
solute carrier family 16, member 3 (monocarboxylic acid transporter 4)
solute carrier family 16 (monocarboxylate transporter), member 3
Alias_symbol (synonym)MCT3
MCT4
Other aliasMGC138472
MGC138474
HGNC (Hugo) SLC16A3
LocusID (NCBI) 9123
Atlas_Id 44573
Location 17q25.3  [Link to chromosome band 17q25]
Location_base_pair Starts at 80186282 and ends at 80197375 bp from pter ( according to hg19-Feb_2009)  [Mapping SLC16A3.png]
Fusion genes
(updated 2016)
BAIAP2 (17q25.3) / SLC16A3 (17q25.3)HEXDC (17q25.3) / SLC16A3 (17q25.3)SLC16A3 (17q25.3) / FTH1 (11q12.3)
SLC16A3 (17q25.3) / MRPL4 (19p13.2)SLC16A3 (17q25.3) / RNF213 (17q25.3)SLC16A3 (17q25.3) / SLC16A3 (17q25.3)

DNA/RNA

Note SLC16A3 was first cloned from human circulating blood by Price et al. (1998).
Description 11077 bp lenght, 5 exons.
Transcription 3 transcripts have been described for this gene (all with protein product): SLC16A3-201, (5 exons; 2033 bps transcript length; 465 residues translation length); SLC16A3-202 (4 exons; 4222 bps transcript length; 465 residues translation length); SLC16A3-203 (5 exons; 2054 bps transcript length; 465 residues translation length).

Protein

 
  Protein diagram drawn following UniProtKB/Swiss-Prot database prediction, using TMRPres2D software.
Description 465 residues; 49469 Da; 12 transmembrane domains; intracellular N- and C-terminals.
Expression SLC16A3/MCT4 is expressed in tissues such as white skeletal muscle fibres, astrocytes, white blood cells, chondrocytes, testis, lung, placenta, heart and some mammalian cell lines (Halestrap and Meredith, 2004; Meredith and Christian, 2008).
Localisation Plasma membrane.
Function Proton-linked monocarboxylate transporter. Catalyzes plasma membrane transport of monocarboxylates such as lactate, pyruvate, branched-chain oxo acids derived from leucine, valine and isoleucine, and the ketone bodies acetoacetate, beta-hydroxybutyrate and acetate.
Homology Belongs to the major facilitator superfamily (MFS). Monocarboxylate porter (TC 2.A.1.13) family. The SLC16A3 gene is conserved in chimpanzee, dog, cow, mouse, rat, chicken, zebrafish, and M. grisea.

Implicated in

Note
  
Entity Colorectal carcinoma
Note SLC16A3/MCT4 protein is overexpressed in colorectal cancer (Pinheiro et al., 2008a).
  
  
Entity Cervical cancer
Note SLC16A3/MCT4 protein is overexpressed in cervical cancer (Pinheiro et al., 2008b). SLC16A3/MCT4 protein overexpression in cervical cancer correlated with positivity for high-risk HPV (Pinheiro et al., 2008b).
  
  
Entity Bladder cancer
Note SLC16A3 gene expression was upregulated in some bladder tumours and induced by hypoxia in bladder cancer cell lines, but not in cultures of normal urothelium (Ord et al., 2005).
  
  
Entity Breast cancer
Note Induction was also seen in two breast cancer cell lines. Expression of SLC16A3 gene is higher in breast cancer distant metastasis as compared to primary tumours or regional metastasis. SLC16A3 gene was then included in the 'VEGF profile' of breast cancer, associated with promotion of vessel formation, survival under anaerobic conditions and loss of dependence upon fibroblasts (Hu et al., 2009).
  
  
Entity Ovarian cancer
Note SLC16A3 gene expression was described to be downregulated in malignant ovarian tumours as compared to normal ovarian surface epithelial cells. Additionally, the non-tumorigenic cell line TOV-81D presented higher expression that tumorigenic cell lines (Wojnarowicz et al., 2008).
SLC16A3 gene, among other transporter genes, was differentially expressed in a chemotherapy resistant ovarian cancer cell line and tumour tissue as compared to a chemosensitive cell line and tumour tissue. It was suggested that these transporters might be involved in drug influx/efflux, modulating chemotherapy response (Cheng et al., 2010).
  
  
Entity Mitochondrial myopathy
Note SLC16A3/MCT4 overexpression was described in a patient with a mitochondrial myopathy (Baker et al., 2001).
  
  
Entity Chronic obstructive pulmonary disease
Note SLC16A3/MCT4 downregulation was described in the vastus lateralis muscle of patients with chronic obstructive pulmonary disease as compared with healthy controls (Green et al., 2008).
  

Bibliography

Expression of MCT1 and MCT4 in a patient with mitochondrial myopathy.
Baker SK, Tarnopolsky MA, Bonen A.
Muscle Nerve. 2001 Mar;24(3):394-8.
PMID 11353425
 
Analysis of chemotherapy response programs in ovarian cancers by the next-generation sequencing technologies.
Cheng L, Lu W, Kulkarni B, Pejovic T, Yan X, Chiang JH, Hood L, Odunsi K, Lin B.
Gynecol Oncol. 2010 Feb 22. [Epub ahead of print]
PMID 20181382
 
Altered metabolic and transporter characteristics of vastus lateralis in chronic obstructive pulmonary disease.
Green HJ, Burnett ME, D'Arsigny CL, O'Donnell DE, Ouyang J, Webb KA.
J Appl Physiol. 2008 Sep;105(3):879-86. Epub 2008 Jul 17.
PMID 18635880
 
The SLC16 gene family-from monocarboxylate transporters (MCTs) to aromatic amino acid transporters and beyond.
Halestrap AP, Meredith D.
Pflugers Arch. 2004 Feb;447(5):619-28. Epub 2003 May 9.
PMID 12739169
 
A compact VEGF signature associated with distant metastases and poor outcomes.
Hu Z, Fan C, Livasy C, He X, Oh DS, Ewend MG, Carey LA, Subramanian S, West R, Ikpatt F, Olopade OI, van de Rijn M, Perou CM.
BMC Med. 2009 Mar 16;7:9.
PMID 19291283
 
The SLC16 monocaboxylate transporter family.
Meredith D, Christian HC.
Xenobiotica. 2008 Jul;38(7-8):1072-106. (REVIEW)
PMID 18668440
 
Comparison of hypoxia transcriptome in vitro with in vivo gene expression in human bladder cancer.
Ord JJ, Streeter EH, Roberts IS, Cranston D, Harris AL.
Br J Cancer. 2005 Aug 8;93(3):346-54.
PMID 16052224
 
Increasing expression of monocarboxylate transporters 1 and 4 along progression to invasive cervical carcinoma.
Pinheiro C, Longatto-Filho A, Ferreira L, Pereira SM, Etlinger D, Moreira MA, Jube LF, Queiroz GS, Schmitt F, Baltazar F.
Int J Gynecol Pathol. 2008b Oct;27(4):568-74.
PMID 18753962
 
Cloning and sequencing of four new mammalian monocarboxylate transporter (MCT) homologues confirms the existence of a transporter family with an ancient past.
Price NT, Jackson VN, Halestrap AP.
Biochem J. 1998 Jan 15;329 ( Pt 2):321-8.
PMID 9425115
 
Construction of a chromosome 17 transcriptome in serous ovarian cancer identifies differentially expressed genes.
Wojnarowicz PM, Breznan A, Arcand SL, Filali-Mouhim A, Provencher DM, Mes-Masson AM, Tonin PN.
Int J Gynecol Cancer. 2008 Sep-Oct;18(5):963-75. Epub 2007 Nov 20.
PMID 18028382
 

Citation

This paper should be referenced as such :
Pinheiro, C ; Baltazar, F
SLC16A3 (solute carrier family 16, member 3 (monocarboxylic acid transporter 4))
Atlas Genet Cytogenet Oncol Haematol. 2010;14(12):1157-1159.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/SLC16A3ID44573ch17q25.html


External links

Nomenclature
HGNC (Hugo)SLC16A3   10924
Cards
AtlasSLC16A3ID44573ch17q25
Entrez_Gene (NCBI)SLC16A3  9123  solute carrier family 16 member 3
AliasesMCT; MCT; MCT-3; MCT-4; 
MCT3; MCT4
GeneCards (Weizmann)SLC16A3
Ensembl hg19 (Hinxton)ENSG00000141526 [Gene_View]  chr17:80186282-80197375 [Contig_View]  SLC16A3 [Vega]
Ensembl hg38 (Hinxton)ENSG00000141526 [Gene_View]  chr17:80186282-80197375 [Contig_View]  SLC16A3 [Vega]
ICGC DataPortalENSG00000141526
TCGA cBioPortalSLC16A3
AceView (NCBI)SLC16A3
Genatlas (Paris)SLC16A3
WikiGenes9123
SOURCE (Princeton)SLC16A3
Genetics Home Reference (NIH)SLC16A3
Genomic and cartography
GoldenPath hg19 (UCSC)SLC16A3  -     chr17:80186282-80197375 +  17q25.3   [Description]    (hg19-Feb_2009)
GoldenPath hg38 (UCSC)SLC16A3  -     17q25.3   [Description]    (hg38-Dec_2013)
EnsemblSLC16A3 - 17q25.3 [CytoView hg19]  SLC16A3 - 17q25.3 [CytoView hg38]
Mapping of homologs : NCBISLC16A3 [Mapview hg19]  SLC16A3 [Mapview hg38]
OMIM603877   
Gene and transcription
Genbank (Entrez)AA448579 AK127319 AK223040 BC112267 BC112269
RefSeq transcript (Entrez)NM_001042422 NM_001042423 NM_001206950 NM_001206951 NM_001206952 NM_004207
RefSeq genomic (Entrez)NC_000017 NC_018928 NT_010663 NW_004929408
Consensus coding sequences : CCDS (NCBI)SLC16A3
Cluster EST : UnigeneHs.500761 [ NCBI ]
CGAP (NCI)Hs.500761
Alternative Splicing GalleryENSG00000141526
Gene ExpressionSLC16A3 [ NCBI-GEO ]   SLC16A3 [ EBI - ARRAY_EXPRESS ]   SLC16A3 [ SEEK ]   SLC16A3 [ MEM ]
Gene Expression Viewer (FireBrowse)SLC16A3 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)9123
GTEX Portal (Tissue expression)SLC16A3
Protein : pattern, domain, 3D structure
UniProt/SwissProtO15427   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO15427  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO15427
Splice isoforms : SwissVarO15427
PhosPhoSitePlusO15427
Domaine pattern : Prosite (Expaxy)MFS (PS50850)   
Domains : Interpro (EBI)MCT    MCT4    MFS    MFS_dom   
Domain families : Pfam (Sanger)MFS_1 (PF07690)   
Domain families : Pfam (NCBI)pfam07690   
Conserved Domain (NCBI)SLC16A3
DMDM Disease mutations9123
Blocks (Seattle)SLC16A3
SuperfamilyO15427
Human Protein AtlasENSG00000141526
Peptide AtlasO15427
HPRD04854
IPIIPI00006666   
Protein Interaction databases
DIP (DOE-UCLA)O15427
IntAct (EBI)O15427
FunCoupENSG00000141526
BioGRIDSLC16A3
STRING (EMBL)SLC16A3
ZODIACSLC16A3
Ontologies - Pathways
QuickGOO15427
Ontology : AmiGOprotein binding  plasma membrane  plasma membrane  integral component of plasma membrane  pyruvate metabolic process  monocarboxylic acid transmembrane transporter activity  lactate transmembrane transporter activity  lactate transmembrane transporter activity  symporter activity  actin cytoskeleton  monocarboxylic acid transport  membrane  nuclear membrane  plasma membrane lactate transport  poly(A) RNA binding  leukocyte migration  
Ontology : EGO-EBIprotein binding  plasma membrane  plasma membrane  integral component of plasma membrane  pyruvate metabolic process  monocarboxylic acid transmembrane transporter activity  lactate transmembrane transporter activity  lactate transmembrane transporter activity  symporter activity  actin cytoskeleton  monocarboxylic acid transport  membrane  nuclear membrane  plasma membrane lactate transport  poly(A) RNA binding  leukocyte migration  
REACTOMEO15427 [protein]
REACTOME Pathways210991 [pathway]   433692 [pathway]   70268 [pathway]   
NDEx NetworkSLC16A3
Atlas of Cancer Signalling NetworkSLC16A3
Wikipedia pathwaysSLC16A3
Orthology - Evolution
OrthoDB9123
GeneTree (enSembl)ENSG00000141526
Phylogenetic Trees/Animal Genes : TreeFamSLC16A3
HOVERGENO15427
HOGENOMO15427
Homologs : HomoloGeneSLC16A3
Homology/Alignments : Family Browser (UCSC)SLC16A3
Gene fusions - Rearrangements
Fusion : MitelmanSLC16A3/MRPL4 [17q25.3/19p13.2]  
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerSLC16A3 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)SLC16A3
dbVarSLC16A3
ClinVarSLC16A3
1000_GenomesSLC16A3 
Exome Variant ServerSLC16A3
ExAC (Exome Aggregation Consortium)SLC16A3 (select the gene name)
Genetic variants : HAPMAP9123
Genomic Variants (DGV)SLC16A3 [DGVbeta]
DECIPHER (Syndromes)17:80186282-80197375  ENSG00000141526
CONAN: Copy Number AnalysisSLC16A3 
Mutations
ICGC Data PortalSLC16A3 
TCGA Data PortalSLC16A3 
Broad Tumor PortalSLC16A3
OASIS PortalSLC16A3 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICSLC16A3  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDSLC16A3
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD - Leiden Open Variation Database
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch SLC16A3
DgiDB (Drug Gene Interaction Database)SLC16A3
DoCM (Curated mutations)SLC16A3 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)SLC16A3 (select a term)
intoGenSLC16A3
NCG5 (London)SLC16A3
Cancer3DSLC16A3(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM603877   
Orphanet
MedgenSLC16A3
Genetic Testing Registry SLC16A3
NextProtO15427 [Medical]
TSGene9123
GENETestsSLC16A3
Huge Navigator SLC16A3 [HugePedia]
snp3D : Map Gene to Disease9123
BioCentury BCIQSLC16A3
ClinGenSLC16A3
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD9123
Chemical/Pharm GKB GenePA35815
Clinical trialSLC16A3
Miscellaneous
canSAR (ICR)SLC16A3 (select the gene name)
Probes
Litterature
PubMed21 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineSLC16A3
EVEXSLC16A3
GoPubMedSLC16A3
iHOPSLC16A3
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Tue Mar 14 13:49:32 CET 2017

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