slc7a10a (solute carrier family 7 member 10a) is one of two zebrafish co-orthologs of vertebrate SLC7A10 (Asc-1), retained from the teleost-specific genome duplication; its paralog is slc7a10b. It encodes a 12-helix light subunit of the heterodimeric amino acid transporters. In mammals Asc-1 is disulfide-linked to the heavy chain 4F2hc (SLC3A2) and mediates sodium-independent exchange of small neutral amino acids, including glycine, L-serine, L-alanine and D-serine; it supplies glycine for inhibitory synapses in the brainstem and spinal cord, regulates D-serine levels, and in adipocytes supports serine uptake and limits lipid storage. slc7a10a keeps every Asc-1 residue shown to matter for substrate binding and gating and the cysteine that links the heavy chain. It is the more broadly expressed copy, rising in larvae and detected in adult brain, bone, heart, kidney, muscle and other tissues. No functional study of slc7a10a has been published.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Plasma membrane propagated from the heterodimeric amino acid transporter light-chain node PTN000208507. Reason: Asc-1 and the other light chains reach the plasma membrane as heterodimers with a heavy chain; slc7a10a keeps the heavy-chain-linking cysteine (human C154) and all 12 transmembrane helices. Location of the core function. Supporting Evidence: PMID:10734121 Asc-1 required 4F2hc for its functional expression. file:DANRE/slc7a10a/slc7a10a-bioinformatics/RESULTS.md No copy has lost a known substrate-site, gating or heavy-chain-linking residue. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Plasma membrane from the UniProt subcellular location (ARBA rule). Reason: Same as the IBA row. Supporting Evidence: PMID:10734121 Asc-1 required 4F2hc for its functional expression. |
| GO:0015175 neutral L-amino acid transmembrane transporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: Neutral L-amino acid transporter activity from node PTN001369926 (human SLC7A10, SLC7A5, SLC7A8). Reason: This is the defining activity of Asc-1 (glycine, alanine, serine, threonine, cysteine), and human SLC7A10 is among the donors. slc7a10a keeps the substrate-pocket and gate residues of human Asc-1. Core function. Supporting Evidence: PMID:10734121 Asc-1 preferred small neutral amino acids such as Gly, L-Ala, L-Ser, L-Thr, and L-Cys, and alpha-aminoisobutyric acid as substrates. file:DANRE/slc7a10a/slc7a10a-bioinformatics/RESULTS.md No copy has lost a known substrate-site, gating or heavy-chain-linking residue. |
| GO:0015179 L-amino acid transmembrane transporter activity | IBA GO_REF:0000033 | ACCEPT | Summary: L-amino acid transporter activity from the light-chain node PTN000208507. Reason: Correct parent of the neutral L-amino acid activity; the node covers light chains with different substrate classes, so this broader term is the right level there. Supporting Evidence: PMID:10734121 Asc-1 preferred small neutral amino acids such as Gly, L-Ala, L-Ser, L-Thr, and L-Cys, and alpha-aminoisobutyric acid as substrates. |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: Membrane from the amino acid permease InterPro entry. Reason: Correct but general; plasma membrane is the specific location. Supporting Evidence: file:DANRE/slc7a10a/slc7a10a-bioinformatics/RESULTS.md both have 12 predicted transmembrane helices (UniProt). |
| GO:0022857 transmembrane transporter activity | IEA GO_REF:0000002 | ACCEPT | Summary: Transmembrane transporter activity from IPR002293. Reason: Correct but very general; the IBA rows give the specific neutral amino acid activity. Supporting Evidence: PMID:10734121 Asc-1 preferred small neutral amino acids such as Gly, L-Ala, L-Ser, L-Thr, and L-Cys, and alpha-aminoisobutyric acid as substrates. |
| GO:0042941 D-alanine transmembrane transport | IBA GO_REF:0000033 | ACCEPT | Summary: D-alanine transmembrane transport from the Asc-1 node PTN002623424. Reason: Asc-1 transports the D-isomers of small neutral amino acids. The substrate pocket residues are conserved in slc7a10a, so the node placement holds for this copy. Supporting Evidence: PMID:10734121 Asc-1 also transported D-isomers of the small neutral amino acids, in particular D-Ser, a putative endogenous modulator of N-methyl-D-aspartate-type glutamate receptors, with high affinity. |
| GO:0042942 D-serine transmembrane transport | IBA GO_REF:0000033 | ACCEPT | Summary: D-serine transmembrane transport from the Asc-1 node PTN002623424. Reason: D-serine is a high-affinity Asc-1 substrate, and Asc-1 transports it in brain; the cryo-EM structure has D-serine bound in the substrate pocket, whose residues are conserved in slc7a10a. Supporting Evidence: PMID:10734121 Asc-1 also transported D-isomers of the small neutral amino acids, in particular D-Ser, a putative endogenous modulator of N-methyl-D-aspartate-type glutamate receptors, with high affinity. PMID:38589439 Middle: Asc-1 adopts an inward open conformation with D-Ser bound in the center of the substrate binding pocket. |
| GO:0055085 transmembrane transport | IEA GO_REF:0000002 | ACCEPT | Summary: Transmembrane transport from IPR002293. Reason: Correct but general. Supporting Evidence: PMID:10734121 Asc-1-mediated transport was not dependent on the presence of Na(+) or Cl(-). |
| GO:1902475 L-alpha-amino acid transmembrane transport | IEA GO_REF:0000108 | ACCEPT | Summary: L-alpha-amino acid transmembrane transport inferred from the L-amino acid transporter activity. Reason: Follows from the accepted activity. Supporting Evidence: PMID:25755256 Asc-1 works as a glycine and L-serine transporter, and its transport activity is required for the subsequent conversion of L-serine into glycine in vivo. |
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Download this section (compressed HTML)Q: Is the broad slc7a10a expression (heart, kidney, muscle, intestine) a teleost gain, or the ancestral pattern that gar Bgee data miss? Mammalian SLC7A10 is expressed in several peripheral tissues.
Q: Which copy supplies glycine at inhibitory synapses of the zebrafish hindbrain and spinal cord, the role that makes mouse Slc7a10 essential?
Q: Which slc3a2 paralog (slc3a2a or slc3a2b) partners each Slc7a10 copy?
Experiment: Co-express each zebrafish Slc7a10 copy with zebrafish slc3a2a in Xenopus oocytes and compare uptake and exchange of glycine, L-serine, L-alanine and D-serine.
Hypothesis: The two copies are equivalent transporters.
Type: transport assay
Experiment: Make single and double mutants (including a promoter-deletion allele to avoid transcriptional adaptation) and test startle and touch-evoked escape behaviour and spinal glycine levels, as for mouse Slc7a10 knockouts.
Hypothesis: slc7a10a and slc7a10b act redundantly in glycinergic neurotransmission.
Type: knockout phenotyping
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