P53986 · MOT1_MOUSE
- ProteinMonocarboxylate transporter 1
- GeneSlc16a1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids493 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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.(S)-lactate (in)CHEBI:16651
+ H+ (in)CHEBI:15378= (S)-lactate (out)CHEBI:16651+ H+ (out)CHEBI:15378 - 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.
GO annotations
Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameMonocarboxylate transporter 1
- Short namesMCT 1
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP53986
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-22 | Cytoplasmic | ||||
Sequence: MPPAIGGPVGYTPPDGGWGWAV | ||||||
Transmembrane | 23-44 | Helical; Name=1 | ||||
Sequence: LVGAFISIGFSYAFPKSITVFF | ||||||
Topological domain | 45-55 | Extracellular | ||||
Sequence: KEIEVIFSATT | ||||||
Transmembrane | 56-80 | Helical; Name=2 | ||||
Sequence: SEVSWISSIMLAVMYAGGPISSILV | ||||||
Topological domain | 81-84 | Cytoplasmic | ||||
Sequence: NKYG | ||||||
Transmembrane | 85-105 | Helical; Name=3 | ||||
Sequence: SRPVMIAGGCLSGCGLIAASF | ||||||
Topological domain | 106-109 | Extracellular | ||||
Sequence: CNTV | ||||||
Transmembrane | 110-132 | Helical; Name=4 | ||||
Sequence: QELYLCIGVIGGLGLAFNLNPAL | ||||||
Topological domain | 133-146 | Cytoplasmic | ||||
Sequence: TMIGKYFYKKRPLA | ||||||
Transmembrane | 147-169 | Helical; Name=5 | ||||
Sequence: NGLAMAGSPVFLSTLAPLNQAFF | ||||||
Topological domain | 170-174 | Extracellular | ||||
Sequence: DIFDW | ||||||
Transmembrane | 175-194 | Helical; Name=6 | ||||
Sequence: RGSFLILGGLLLNCCVAGSL | ||||||
Topological domain | 195-254 | Cytoplasmic | ||||
Sequence: MRPIGPEQVKLEKLKSKESLQEAGKSDANTDLIGGSPKGEKLSVFQTINKFLDLSLFTHR | ||||||
Transmembrane | 255-281 | Helical; Name=7 | ||||
Sequence: GFLLYLSGNVVMFFGLFTPLVFLSSYG | ||||||
Topological domain | 282-288 | Extracellular | ||||
Sequence: KSKDFSS | ||||||
Transmembrane | 289-310 | Helical; Name=8 | ||||
Sequence: EKSAFLLSILAFVDMVARPSMG | ||||||
Topological domain | 311-321 | Cytoplasmic | ||||
Sequence: LAANTKWIRPR | ||||||
Transmembrane | 322-342 | Helical; Name=9 | ||||
Sequence: IQYFFAASVVANGVCHLLAPL | ||||||
Topological domain | 343-346 | Extracellular | ||||
Sequence: STTY | ||||||
Transmembrane | 347-368 | Helical; Name=10 | ||||
Sequence: VGFCVYAGVFGFAFGWLSSVLF | ||||||
Topological domain | 369-382 | Cytoplasmic | ||||
Sequence: ETLMDLIGPQRFSS | ||||||
Transmembrane | 383-403 | Helical; Name=11 | ||||
Sequence: AVGLVTIVECCPVLLGPPLLG | ||||||
Topological domain | 404-414 | Extracellular | ||||
Sequence: RLNDMYGDYKY | ||||||
Transmembrane | 415-436 | Helical; Name=12 | ||||
Sequence: TYWACGVILIIAGIYLFIGMGI | ||||||
Topological domain | 437-493 | Cytoplasmic | ||||
Sequence: NYRLLAKEQKAEEKQKREGKEDEASTDVDEKPKETMKAAQSPQQHSSGDPTEEESPV |
Keywords
- Cellular component
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.
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000211383 | 1-493 | Monocarboxylate transporter 1 | |||
Sequence: MPPAIGGPVGYTPPDGGWGWAVLVGAFISIGFSYAFPKSITVFFKEIEVIFSATTSEVSWISSIMLAVMYAGGPISSILVNKYGSRPVMIAGGCLSGCGLIAASFCNTVQELYLCIGVIGGLGLAFNLNPALTMIGKYFYKKRPLANGLAMAGSPVFLSTLAPLNQAFFDIFDWRGSFLILGGLLLNCCVAGSLMRPIGPEQVKLEKLKSKESLQEAGKSDANTDLIGGSPKGEKLSVFQTINKFLDLSLFTHRGFLLYLSGNVVMFFGLFTPLVFLSSYGKSKDFSSEKSAFLLSILAFVDMVARPSMGLAANTKWIRPRIQYFFAASVVANGVCHLLAPLSTTYVGFCVYAGVFGFAFGWLSSVLFETLMDLIGPQRFSSAVGLVTIVECCPVLLGPPLLGRLNDMYGDYKYTYWACGVILIIAGIYLFIGMGINYRLLAKEQKAEEKQKREGKEDEASTDVDEKPKETMKAAQSPQQHSSGDPTEEESPV | ||||||
Modified residue | 210 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 213 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 220 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 224 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 230 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 461 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 462 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 477 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 482 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 483 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 491 | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
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
Structure
Family & Domains
Features
Showing features for compositional bias, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 447-472 | Basic and acidic residues | ||||
Sequence: AEEKQKREGKEDEASTDVDEKPKETM | ||||||
Region | 447-493 | Disordered | ||||
Sequence: AEEKQKREGKEDEASTDVDEKPKETMKAAQSPQQHSSGDPTEEESPV | ||||||
Compositional bias | 473-493 | Polar residues | ||||
Sequence: KAAQSPQQHSSGDPTEEESPV |
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length493
- Mass (Da)53,267
- Last updated1996-10-01 v1
- Checksum8B6DAB7741340DD7
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 447-472 | Basic and acidic residues | ||||
Sequence: AEEKQKREGKEDEASTDVDEKPKETM | ||||||
Compositional bias | 473-493 | Polar residues | ||||
Sequence: KAAQSPQQHSSGDPTEEESPV |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |