id: A0A9L0JV53 gene_symbol: SLC16A11 product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:9793 label: Equus asinus description: SLC16A11 encodes monocarboxylate transporter 11 (MCT11), a member of the proton-linked monocarboxylate transporter family (SLC16) of the major facilitator superfamily. In human, MCT11 is a twelve-helix membrane transporter that moves pyruvate together with a proton across the plasma membrane; it pairs with the ancillary protein basigin (BSG), which promotes its delivery to the cell surface, although most of the protein resides in the endoplasmic reticulum membrane. It is expressed in liver, salivary gland and thyroid, influences hepatic lipid metabolism, and variants that lower its expression or cell-surface level raise type 2 diabetes risk. In mouse, MCT11 is induced in exhausted CD8+ T cells in tumours, where it mediates lactic acid uptake. The donkey gene (Ensembl ENSEASG00005017919) has several UniProt transcript models; this entry, A0A9L0JV53, is an alternative transcript model whose C-terminal 332 residues match the full-length donkey MCT11 model (A0A8C4PS96) exactly, but whose first 107 residues are an unrelated sequence, so it lacks the first three transmembrane helices. existing_annotations: - term: id: GO:0005789 label: endoplasmic reticulum membrane evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in supporting_entities: - UniProtKB-SubCell:SL-0097 review: summary: ER membrane, from the UniProt subcellular location mapping (from an ARBA rule in this donkey entry). Tagged human MCT11 co-localizes with calnexin in the ER, and most of the protein is in intracellular membranes. action: ACCEPT reason: The localization is experimentally established for the human ortholog, and the donkey gene belongs to the same PANTHER subfamily (PTHR11360:SF80, MONOCARBOXYLATE TRANSPORTER 11) as a 1:1 ortholog. The donkey entry shares its C-terminal 332 residues exactly with the full-length donkey model. The annotation describes the gene product. Whether this N-terminally altered transcript model is itself retained in the ER is not known. supported_by: - reference_id: PMID:24390345 supporting_text: SLC16A11-V5 co-localizes with the endoplasmic reticulum membrane protein Calnexin, but shows minimal overlap with plasma membrane, Golgi apparatus and mitochondria - reference_id: PMID:28666119 supporting_text: the majority of SLC16A11REF-V5 is associated with intracellular membranes, with a portion (~5%) localized to the plasma membrane - term: id: GO:0005886 label: plasma membrane evidence_type: IEA original_reference_id: GO_REF:0000044 qualifier: located_in supporting_entities: - UniProtKB-SubCell:SL-0039 review: summary: Plasma membrane, from the UniProt subcellular location mapping. Human MCT11 transports pyruvate across the plasma membrane, and BSG is needed for its cell-surface localization. action: ACCEPT reason: Only a small fraction of the protein is at the cell surface, but the transport activity was measured there, the PANTHER family root carries plasma membrane by PAINT IBD with human MCT11 (Q8NCK7) among the seeds, and T2D-risk coding variants that reduce plasma membrane localization reduce MCT11 function. This is where the core activity is carried out. supported_by: - reference_id: PMID:28666119 supporting_text: We found that BSG knockout significantly reduces localization of SLC16A11REF to the plasma membrane - reference_id: PMID:28666119 supporting_text: disrupting a key interaction with basigin, thereby reducing cell-surface localization - term: id: GO:0008028 label: monocarboxylic acid transmembrane transporter activity evidence_type: IEA original_reference_id: GO_REF:0000118 qualifier: enables supporting_entities: - PANTHER:PTN008966426 review: summary: TreeGrafter transfer of monocarboxylic acid transmembrane transporter activity. PAINT curators placed this term at the MCT-family node PTN000888455, with human MCT11 among the experimental seeds. Human MCT11 moves pyruvate with a proton, and mouse MCT11 mediates lactic acid uptake. action: ACCEPT reason: The activity is placed at a deep PAINT node of the family, the donkey gene sits inside that clade in the MCT11 subfamily (SF80), and the substrate class is supported in two species (pyruvate for human, lactate for mouse). This is the precise level the evidence supports for the gene. Curators did not propagate the narrower pyruvate transporter term from the human IDA, and MCT11 also takes up lactate, so the family-level term is kept rather than narrowed. The A0A9L0JV53 polypeptide itself lacks TM1-TM3 and is unlikely to transport on its own; this is a property of the transcript model, while the full-length donkey model (A0A8C4PS96) has the complete fold. supported_by: - reference_id: PMID:28666119 supporting_text: These results support a H+-coupled mechanism underlying SLC16A11 transport - reference_id: PMID:39516648 supporting_text: Conditional deletion of MCT11 in T cells reduced lactic acid uptake by Tex cells - reference_id: file:EQUAS/SLC16A11/SLC16A11-bioinformatics/RESULTS-rereview.md supporting_text: Its residues 108-439 are identical to A0A8C4PS96 residues 189-520, which correspond to human residues 116-447. - term: id: GO:0015718 label: monocarboxylic acid transport evidence_type: IEA original_reference_id: GO_REF:0000118 qualifier: involved_in supporting_entities: - PANTHER:PTN008966426 review: summary: TreeGrafter transfer of monocarboxylic acid transport, the process counterpart of the transporter activity. action: ACCEPT reason: The transporter performs the transport step itself, so this is direct participation, not a downstream effect. Pyruvate and lactate are both monocarboxylates. supported_by: - reference_id: PMID:28666119 supporting_text: HEK293T cells co-transfected with pyronic and either empty vector control or SLC16A11REF-V5 (Figure S3B) were exposed to pyruvate, resulting in an increase of the fluorescence signal indicative of pyruvate uptake - term: id: GO:0022857 label: transmembrane transporter activity evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: enables supporting_entities: - InterPro:IPR011701 review: summary: InterPro2GO mapping from the MFS domain entry. PAINT also places this term at the family root node. action: TOO_GENERAL reason: True, but monocarboxylic acid transmembrane transporter activity, accepted in this review, is a descendant and entails it. - term: id: GO:0055085 label: transmembrane transport evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: involved_in supporting_entities: - InterPro:IPR011701 review: summary: InterPro2GO mapping from the MFS domain entry. action: TOO_GENERAL reason: True, but the accepted monocarboxylic acid transmembrane transporter activity already entails transmembrane transport, and the accepted monocarboxylic acid transport row states the specific process. references: - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - id: GO_REF:0000044 title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt findings: [] - id: GO_REF:0000118 title: TreeGrafter-generated GO annotations findings: [] - id: PMID:24390345 title: Sequence variants in SLC16A11 are a common risk factor for type 2 diabetes in Mexico. findings: - statement: Tagged human SLC16A11 localizes to the endoplasmic reticulum in HeLa cells, and the gene is expressed in liver, salivary gland and thyroid. supporting_text: we observed SLC16A11 expression in liver, salivary gland, and thyroid reference_review: relevance: HIGH correctness: VERIFIED review_notes: Full text cached. Source of the human ER localization (IDA) and tissue expression; the metabolic profiling (TAG increase on overexpression) is the basis of the human lipid metabolic process IDA, which PAINT did not propagate and which this review does not transfer. - id: PMID:28666119 title: Type 2 Diabetes Variants Disrupt Function of SLC16A11 through Two Distinct Mechanisms. findings: - statement: Human SLC16A11 is a proton-coupled monocarboxylate transporter that moves pyruvate across the plasma membrane. supporting_text: These results support a H+-coupled mechanism underlying SLC16A11 transport - statement: BSG is required for plasma membrane localization of SLC16A11, and T2D-risk coding variants disrupt the BSG interaction. supporting_text: We found that BSG knockout significantly reduces localization of SLC16A11REF to the plasma membrane reference_review: relevance: HIGH correctness: VERIFIED review_notes: Full text cached. Primary evidence for the transport activity, proton coupling, BSG dependence and plasma membrane localization of human MCT11. - id: PMID:39516648 title: Dysfunction of exhausted T cells is enforced by MCT11-mediated lactate metabolism. findings: - statement: Mouse MCT11 is upregulated in terminally exhausted CD8+ T cells and mediates their lactic acid uptake. supporting_text: Conditional deletion of MCT11 in T cells reduced lactic acid uptake by Tex cells reference_review: relevance: HIGH correctness: VERIFIED review_notes: Full text cached. Independent mouse genetic evidence that MCT11 transports a monocarboxylate (lactate) in vivo; supports keeping the family-level substrate term rather than narrowing it to pyruvate. - id: PMID:30673611 title: Gain-of-Function Mutations of SLC16A11 Contribute to the Pathogenesis of Type 2 Diabetes. findings: [] reference_review: relevance: MEDIUM correctness: DISPUTED review_notes: Abstract only. Slc16a11 knockout mice have no significant metabolic defect, and the authors argue that the T2D variants act by gain of function; this is contested by PMID:31618643. Used as background only, not as support for any annotation. - id: PMID:31618643 title: Gain-of-Function Claims for Type-2-Diabetes-Associated Coding Variants in SLC16A11 Are Not Supported by the Experimental Data. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: Abstract only (Matters Arising). Background on the loss- versus gain-of-function dispute about the human T2D variants; not used as support. - id: PMID:31618644 title: Type 2 Diabetes Variants in the SLC16A11 Coding Region Are Not Loss-of-Function Mutations. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: Abstract only (Matters Arising response). Background on the variant-mechanism dispute; not used as support. - id: PMID:31185508 title: Adeno-Associated Virus-Mediated Knockdown of SLC16A11 Improves Glucose Tolerance and Hepatic Insulin Signaling in High Fat Diet-Fed Mice. findings: [] reference_review: relevance: LOW correctness: LOW_QUALITY review_notes: Abstract only. Hepatic knockdown phenotype in diet-fed mice; organismal metabolic phenotype, not evidence for a molecular function or a process the transporter carries out. Not used as support. - id: file:EQUAS/SLC16A11/SLC16A11-uniprot.txt title: UniProt record for donkey SLC16A11 (A0A9L0JV53) findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: The function, location and family statements in this TrEMBL record come from ARBA rules and are not used as evidence; the record is used for the sequence, Phobius helices and PANTHER membership. - id: file:EQUAS/SLC16A11/SLC16A11-bioinformatics/SLC16A11-human-Q8NCK7-uniprot.txt title: UniProt Swiss-Prot record for human SLC16A11 (Q8NCK7) findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Curated human record. In the 2026-10-21 re-review, support was moved to the primary papers it cites (PMID:24390345, PMID:28666119), which are now cached; the record is kept as a reference for the human sequence and curated summary. - id: file:EQUAS/SLC16A11/SLC16A11-bioinformatics/RESULTS.md title: 'SLC16A11: donkey-human sequence comparison' findings: - statement: The donkey gene model lacks the region corresponding to human transmembrane helices 1-3. supporting_text: The human N-terminal region containing predicted transmembrane helices 1-3 (human 12-32, 54-74, 82-102) therefore has no homologous counterpart in the donkey model reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Original pairwise analysis. Its conclusion (TM1-TM3 missing) is confirmed by RESULTS-rereview.md; the earlier wording "misassembled" is refined there, since the N-terminal segment is an alternative 5' exon shared with another Ensembl transcript. - id: file:EQUAS/SLC16A11/SLC16A11-bioinformatics/RESULTS-rereview.md title: 'SLC16A11 (donkey): comparison of all donkey gene models with human MCT11' findings: - statement: Five donkey UniProt entries are transcript models of one Ensembl gene; only A0A8C4PS96 contains the full human MCT11 sequence, and A0A9L0JV53 shares its C-terminal 332 residues exactly with it. supporting_text: A0A8C4PS96 (520 aa) is the only donkey model that contains the whole human MCT11 sequence reference_review: relevance: HIGH correctness: VERIFIED review_notes: Reproducible analysis written for this re-review (compare_gene_models_rereview.py). core_functions: - description: Proton-coupled monocarboxylate transporter of the plasma membrane, delivered to the cell surface with the ancillary protein basigin. Pyruvate (human) and lactate (mouse) are the substrates shown experimentally for the orthologs. molecular_function: id: GO:0008028 label: monocarboxylic acid transmembrane transporter activity directly_involved_in: - id: GO:0015718 label: monocarboxylic acid transport locations: - id: GO:0005886 label: plasma membrane supported_by: - reference_id: PMID:28666119 supporting_text: These results support a H+-coupled mechanism underlying SLC16A11 transport - reference_id: PMID:39516648 supporting_text: Conditional deletion of MCT11 in T cells reduced lactic acid uptake by Tex cells suggested_questions: - question: Which donkey SLC16A11 transcript is the main expressed product? Is the full-length model A0A8C4PS96 (with TM1-TM3) the dominant liver isoform, and is the A0A9L0JV53 transcript, which lacks TM1-TM3, translated at all? - question: Is MCT11 substrate preference conserved across mammals (pyruvate in the human assay, lactate in mouse T cells), and would a more specific substrate term be justified at the MCT11 subfamily level? suggested_experiments: - description: Long-read cDNA sequencing or 5'-RACE of donkey liver SLC16A11 transcripts to establish which 5' exons are used, followed by pyruvate and lactate uptake assays of the full-length donkey protein co-expressed with BSG.