SLC16A11

UniProt ID: A0A9L0JV53
Organism: Equus asinus
Review Status: COMPLETE
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Gene 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 Review

GO Term Evidence Action Reason
GO:0005789 endoplasmic reticulum membrane
IEA
GO_REF:0000044 		ACCEPT
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.
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.
Supporting Evidence:
PMID:24390345
SLC16A11-V5 co-localizes with the endoplasmic reticulum membrane protein Calnexin, but shows minimal overlap with plasma membrane, Golgi apparatus and mitochondria
PMID:28666119
the majority of SLC16A11REF-V5 is associated with intracellular membranes, with a portion (~5%) localized to the plasma membrane
GO:0005886 plasma membrane
IEA
GO_REF:0000044 		ACCEPT
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.
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.
Supporting Evidence:
PMID:28666119
We found that BSG knockout significantly reduces localization of SLC16A11REF to the plasma membrane
PMID:28666119
disrupting a key interaction with basigin, thereby reducing cell-surface localization
GO:0008028 monocarboxylic acid transmembrane transporter activity
IEA
GO_REF:0000118 		ACCEPT
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.
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.
Supporting Evidence:
PMID:28666119
These results support a H+-coupled mechanism underlying SLC16A11 transport
PMID:39516648
Conditional deletion of MCT11 in T cells reduced lactic acid uptake by Tex cells
file:EQUAS/SLC16A11/SLC16A11-bioinformatics/RESULTS-rereview.md
Its residues 108-439 are identical to A0A8C4PS96 residues 189-520, which correspond to human residues 116-447.
GO:0015718 monocarboxylic acid transport
IEA
GO_REF:0000118 		ACCEPT
Summary: TreeGrafter transfer of monocarboxylic acid transport, the process counterpart of the transporter activity.
Reason: The transporter performs the transport step itself, so this is direct participation, not a downstream effect. Pyruvate and lactate are both monocarboxylates.
Supporting Evidence:
PMID:28666119
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
GO:0022857 transmembrane transporter activity
IEA
GO_REF:0000002 		TOO GENERAL
Summary: InterPro2GO mapping from the MFS domain entry. PAINT also places this term at the family root node.
Reason: True, but monocarboxylic acid transmembrane transporter activity, accepted in this review, is a descendant and entails it.
GO:0055085 transmembrane transport
IEA
GO_REF:0000002 		TOO GENERAL
Summary: InterPro2GO mapping from the MFS domain entry.
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.

Core Functions

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:
monocarboxylic acid transmembrane transporter activity
Directly Involved In:
monocarboxylic acid transport
Cellular Locations:
plasma membrane
Supporting Evidence:
  • PMID:28666119
    These results support a H+-coupled mechanism underlying SLC16A11 transport
  • PMID:39516648
    Conditional deletion of MCT11 in T cells reduced lactic acid uptake by Tex cells

References

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Suggested Questions for Experts

Q: 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?

Q: 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

Experiment: 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.

External Prediction Reviews

These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.

ProtNLM2 External predictions

View prediction review YAML · SLC16A11-protnlm-predictions-review.yaml · Review status: COMPLETE

Assessment of the single ProtNLM2 GO prediction for donkey SLC16A11 (A0A9L0JV53), judged against the donkey GOA record (ER membrane, plasma membrane, monocarboxylic acid transmembrane transporter activity, monocarboxylic acid transport, transmembrane transporter activity, transmembrane transport), experimental evidence that human MCT11 (Q8NCK7) is a proton-coupled pyruvate transporter, and donkey-human alignments showing that this gene model lacks the region of transmembrane helices 1-3 while its remaining residues are identical to the full-length donkey model A0A8C4PS96. The prediction, transmembrane transporter activity, is true of the gene but is scored as incorrect for this product (NPI, domain architecture mismatch), because the polypeptide lacks transmembrane helices 1-3 of the transport fold. The frozen ProtNLM2 output contains no non-GO rows (function text or subcellular location) for this accession.

Source documents: projects/PROTNLM_EVALUATION/donkey40/donkey40-predictions.tsv · genes/EQUAS/SLC16A11/SLC16A11-goa.tsv · genes/EQUAS/SLC16A11/SLC16A11-bioinformatics/SLC16A11-human-Q8NCK7-uniprot.txt · genes/EQUAS/SLC16A11/SLC16A11-bioinformatics/RESULTS.md · genes/EQUAS/SLC16A11/SLC16A11-bioinformatics/RESULTS-rereview.md · genes/EQUAS/SLC16A11/SLC16A11-ai-review.yaml · publications/PMID_28666119.md

Review score: 2 = concordant with evidence; 1 = uncertain; 0 = discordant with evidence. This is an assessment score, not a model probability.

GO:0022857 transmembrane transporter activity GO_MF
NPI — Nonparalog incorrect Review score: 0/2
Prediction method: ProtNLM2 · Version: UniProt API snapshot 2026-10-14
DOMAIN ARCHITECTURE MISMATCH
Review rationale: Scored for the A0A9L0JV53 polypeptide, an alternative transcript model of donkey SLC16A11 (MCT11, PANTHER PTHR11360:SF80). Transmembrane transporter activity is true of the gene, since human MCT11 transports pyruvate with a proton and the full-length donkey model A0A8C4PS96 has the complete fold, but this product lacks the region of transmembrane helices 1-3 of the twelve-helix major facilitator fold. Its first 107 residues are an unrelated sequence with no counterpart of human TM1-TM3, and only residues 108-439 (human 116-447) are shared with the full-length model. A major facilitator transporter missing three helices of its N-terminal six-helix bundle lacks part of the translocation pathway, so this exact polypeptide is not expected to transport on its own. The prediction depends on a feature this accession lacks.
Supporting Evidence:

Deep Research

Cyberian

(SLC16A11-deep-research-cyberian.md)

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📚 Additional Documentation

Notes

(SLC16A11-notes.md)

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Bioinformatics Results

(RESULTS.md)

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📄 View Raw YAML

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