P53986 · MOT1_MOUSE

  • Protein
    Monocarboxylate transporter 1
  • Gene
    Slc16a1
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

Function

function

Bidirectional proton-coupled monocarboxylate transporter. Catalyzes the rapid transport across the plasma membrane of many monocarboxylates such as lactate, pyruvate, acetate and the ketone bodies acetoacetate and beta-hydroxybutyrate, and thus contributes to the maintenance of intracellular pH (By similarity).
The transport direction is determined by the proton motive force and the concentration gradient of the substrate monocarboxylate. MCT1 is a major lactate exporter (By similarity).
Plays a role in cellular responses to a high-fat diet by modulating the cellular levels of lactate and pyruvate that contribute to the regulation of central metabolic pathways and insulin secretion, with concomitant effects on plasma insulin levels and blood glucose homeostasis (PubMed:22522610, PubMed:24367518).
Facilitates the protonated monocarboxylate form of succinate export, that its transient protonation upon muscle cell acidification in exercising muscle and ischemic heart. Functions via alternate outward- and inward-open conformation states. Protonation and deprotonation of 302-Asp is essential for the conformational transition (PubMed:32946811).

Miscellaneous

Overexpression in pancreatic beta-cells triggers insulin secretion in response to pyruvate, causing hyperinsulemia and hypoglycemia during strenuous exercise.

Catalytic activity

  • (S)-lactate(in) + H+(in) = (S)-lactate(out) + H+(out)
    This reaction proceeds in the forward
    and the backward
    directions.
  • acetate(out) + H+(out) = acetate(in) + H+(in)
    This reaction proceeds in the forward
    and the backward
    directions.
  • acetoacetate(out) + H+(out) = acetoacetate(in) + H+(in)
    This reaction proceeds in the forward
    and the backward
    directions.
  • H+(out) + pyruvate(out) = H+(in) + pyruvate(in)
  • (R)-3-hydroxybutanoate(out) + H+(out) = (R)-3-hydroxybutanoate(in) + H+(in)
    This reaction proceeds in the forward
    and the backward
    directions.
  • 3-methyl-2-oxobutanoate(out) + H+(out) = 3-methyl-2-oxobutanoate(in) + H+(in)
  • 4-methyl-2-oxopentanoate(out) + H+(out) = 4-methyl-2-oxopentanoate(in) + H+(in)
  • 2 H+(in) + succinate(in) = 2 H+(out) + succinate(out)
    This reaction proceeds in the forward direction.

Features

Showing features for binding site.

TypeIDPosition(s)Description
Binding site38(S)-lactate (UniProtKB | ChEBI)
Binding site302H+ (UniProtKB | ChEBI)
Binding site306(S)-lactate (UniProtKB | ChEBI)

GO annotations

AspectTerm
Cellular Componentapical plasma membrane
Cellular Componentbasolateral plasma membrane
Cellular Componentcentrosome
Cellular Componentlateral plasma membrane
Cellular Componentmitochondrion
Cellular Componentplasma membrane
Cellular Componentsynapse
Molecular Functioncarboxylic acid transmembrane transporter activity
Molecular Functionidentical protein binding
Molecular Functionlactate transmembrane transporter activity
Molecular Functionlactate:proton symporter activity
Molecular Functionmonocarboxylic acid transmembrane transporter activity
Molecular Functionorganic cyclic compound binding
Molecular Functionsolute:proton symporter activity
Molecular Functionsuccinate transmembrane transporter activity
Biological Processbehavioral response to nutrient
Biological Processcarboxylic acid transmembrane transport
Biological Processcellular response to organic cyclic compound
Biological Processcentrosome cycle
Biological Processglucose homeostasis
Biological Processlactate transmembrane transport
Biological Processlipid metabolic process
Biological Processmonocarboxylic acid transport
Biological Processplasma membrane lactate transport
Biological Processpyruvate catabolic process
Biological Processpyruvate transmembrane transport
Biological Processregulation of insulin secretion
Biological Processresponse to food

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Monocarboxylate transporter 1
  • Short names
    MCT 1
  • Alternative names
    • Solute carrier family 16 member 1

Gene names

    • Name
      Slc16a1
    • Synonyms
      Mct1

Organism names

  • Taxonomic identifier
  • Strains
    • 129
    • FVB/N
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    P53986

Proteomes

Organism-specific databases

Subcellular Location

Cell membrane
; Multi-pass membrane protein
Basolateral cell membrane
; Multi-pass membrane protein
Apical cell membrane
; Multi-pass membrane protein
Note: Expression at the cell surface requires the ancillary proteins BSG and EMB.

Features

Showing features for topological domain, transmembrane.

TypeIDPosition(s)Description
Topological domain1-22Cytoplasmic
Transmembrane23-44Helical; Name=1
Topological domain45-55Extracellular
Transmembrane56-80Helical; Name=2
Topological domain81-84Cytoplasmic
Transmembrane85-105Helical; Name=3
Topological domain106-109Extracellular
Transmembrane110-132Helical; Name=4
Topological domain133-146Cytoplasmic
Transmembrane147-169Helical; Name=5
Topological domain170-174Extracellular
Transmembrane175-194Helical; Name=6
Topological domain195-254Cytoplasmic
Transmembrane255-281Helical; Name=7
Topological domain282-288Extracellular
Transmembrane289-310Helical; Name=8
Topological domain311-321Cytoplasmic
Transmembrane322-342Helical; Name=9
Topological domain343-346Extracellular
Transmembrane347-368Helical; Name=10
Topological domain369-382Cytoplasmic
Transmembrane383-403Helical; Name=11
Topological domain404-414Extracellular
Transmembrane415-436Helical; Name=12
Topological domain437-493Cytoplasmic

Keywords

Phenotypes & Variants

Disruption phenotype

Complete lethality during early embryonic development. Heterozygous mice are viable and show no obvious morphological or behavorial phenotype. Heterozygous mice that are kept on a normal diet show normal weight gain, normal glucose tolerance and insulin sensitivity. In contrast, mice exhibit a striking reduction in weight gain relative to wild-type, when kept on a high-fat diet. This is due to reduced fat accumulation in the liver and in subcutaneous white adipose tissue. In addition, heterozygous mice kept on a high-fat diet show higher glucose tolerance and higher insulin sensitivity than wild-type. The reduced weight gain is explained by reduced food intake, less efficient nutrient assimilation in the intestine and increased oxygen consumption when kept on a high-fat diet. Besides, heterozygous mice fail to respond to a high-fat diet by up-regulation of genes involved in lipid metabolism.

Variants

We now provide the "Disease & Variants" viewer in its own tab.

The viewer provides 25 variants from UniProt as well as other sources including ClinVar and dbSNP.

Go to variant viewer

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00002113831-493Monocarboxylate transporter 1
Modified residue210Phosphoserine
Modified residue213Phosphoserine
Modified residue220Phosphoserine
Modified residue224Phosphothreonine
Modified residue230Phosphoserine
Modified residue461Phosphoserine
Modified residue462Phosphothreonine
Modified residue477Phosphoserine
Modified residue482Phosphoserine
Modified residue483Phosphoserine
Modified residue491Phosphoserine

Keywords

Proteomic databases

PTM databases

Expression

Tissue specificity

Detected in liver, brain, spinal cord, spermatozoa, muscle, white adipose tissue and brown adipose tissue (at protein level). Widely expressed, except in pancreas, where expression is not detectable.

Gene expression databases

Interaction

Subunit

Interacts with isoform 2 of BSG; interaction mediates SLC16A1 targeting to the plasma membrane (PubMed:21792931).
Interacts with EMB; interaction mediates SLC16A1 targeting to the plasma membrane (By similarity).

Protein-protein interaction databases

Miscellaneous

Family & Domains

Features

Showing features for compositional bias, region.

TypeIDPosition(s)Description
Compositional bias447-472Basic and acidic residues
Region447-493Disordered
Compositional bias473-493Polar residues

Sequence similarities

Keywords

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    493
  • Mass (Da)
    53,267
  • Last updated
    1996-10-01 v1
  • Checksum
    8B6DAB7741340DD7
MPPAIGGPVGYTPPDGGWGWAVLVGAFISIGFSYAFPKSITVFFKEIEVIFSATTSEVSWISSIMLAVMYAGGPISSILVNKYGSRPVMIAGGCLSGCGLIAASFCNTVQELYLCIGVIGGLGLAFNLNPALTMIGKYFYKKRPLANGLAMAGSPVFLSTLAPLNQAFFDIFDWRGSFLILGGLLLNCCVAGSLMRPIGPEQVKLEKLKSKESLQEAGKSDANTDLIGGSPKGEKLSVFQTINKFLDLSLFTHRGFLLYLSGNVVMFFGLFTPLVFLSSYGKSKDFSSEKSAFLLSILAFVDMVARPSMGLAANTKWIRPRIQYFFAASVVANGVCHLLAPLSTTYVGFCVYAGVFGFAFGWLSSVLFETLMDLIGPQRFSSAVGLVTIVECCPVLLGPPLLGRLNDMYGDYKYTYWACGVILIIAGIYLFIGMGINYRLLAKEQKAEEKQKREGKEDEASTDVDEKPKETMKAAQSPQQHSSGDPTEEESPV

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias447-472Basic and acidic residues
Compositional bias473-493Polar residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
X82438
EMBL· GenBank· DDBJ
CAA57819.1
EMBL· GenBank· DDBJ
mRNA
AF058055
EMBL· GenBank· DDBJ
AAC13720.1
EMBL· GenBank· DDBJ
mRNA
BC014777
EMBL· GenBank· DDBJ
AAH14777.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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