slc7a10b (solute carrier family 7 member 10b) is one of two zebrafish co-orthologs of vertebrate SLC7A10 (Asc-1), retained from the teleost-specific genome duplication; its paralog is slc7a10a. 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, regulates D-serine levels, and in adipocytes supports serine uptake and limits lipid storage. slc7a10b keeps every Asc-1 residue shown to matter for substrate binding and gating and the cysteine that links the heavy chain. It is expressed at low levels, from the blastula stage onward in embryos, and in adult brain, eye, bone and testis, and in zebrafish arachnoid meningeal cells. Zebrafish carrying a slc7a10b loss-of-function allele gain more weight and have larger visceral adipocytes than wild type when overfed.
| 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; slc7a10b 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. slc7a10b 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 slc7a10b, 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 slc7a10b. 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:0097009 energy homeostasis | IMP PMID:33408126 Role of the Neutral Amino Acid Transporter SLC7A10 in Adipoc... | KEEP AS NON CORE | Summary: Energy homeostasis (acts upstream of or within), IMP, from an slc7a10b loss-of-function zebrafish line that gained more weight and had larger visceral adipocytes than wild type when overfed. Reason: The phenotype is real and specific to this copy: slc7a10b mutant fish overfed for two months gained more body weight and had larger visceral adipocytes, matching human and mouse data that adipocyte SLC7A10 limits lipid storage. The transporter acts upstream of this outcome through adipocyte amino acid (serine) uptake, glutathione and ROS, so energy homeostasis is a downstream, organism-level consequence rather than the function of the protein. The authors chose slc7a10b for its slightly higher identity to human SLC7A10, not for its expression, and call the line a partial knockout because slc7a10a remains; the paralog was not examined. Only the abstract of the primary paper is cached, so allele details were read from the same group's review. Supporting Evidence: PMID:33408126 Concordantly, loss of Slc7a10 function in zebrafish in vivo accelerates diet-induced body weight gain and adipocyte enlargement. PMID:36172277 Compared to wildtypes, the fish with impaired Slc7a10b function gained 38% more body weight and had on average 49% larger visceral adipocytes PMID:36172277 Because two isoforms of Slc7a10 exist in zebrafish (Slc7a10a as well as Slc7a10b), this model should be considered a partial global knockout of Slc7a10. PMID:33408126 Mechanistically, SLC7A10 inhibition in human and murine adipocytes decreases adipocyte serine uptake and total glutathione levels and promotes reactive oxygen species (ROS) generation. |
| 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. |
Loading supporting content…
Download this section (compressed HTML)Q: Is the adipose phenotype of slc7a10b mutants specific to this copy, or would slc7a10a or double mutants show the same or a stronger effect? Which copy is expressed in zebrafish adipocytes?
Q: Is slc7a10b transcriptionally upregulated or slc7a10a compensating in the slc7a10b mutant line?
Q: Does slc7a10b, like gar SLC7A10, keep the ancestral neural (brain, eye) and gonadal expression, with slc7a10a having gained peripheral tissues?
Experiment: Paralog-specific HCR in situ or qPCR in sorted zebrafish adipocytes; overfeeding assay on slc7a10a, slc7a10b and double mutants.
Hypothesis: slc7a10a and slc7a10b differ in adipose expression and contribute unequally to lipid storage.
Type: knockout phenotyping
Experiment: Co-express Slc7a10b with zebrafish slc3a2a in Xenopus oocytes and measure glycine, L-serine and D-serine uptake and exchange, side by side with Slc7a10a.
Hypothesis: Slc7a10b is an Asc-type exchanger with the same substrate profile as mammalian Asc-1.
Type: transport assay
Loading supporting content…
Download this section (compressed HTML)Loading supporting content…
Download this section (compressed HTML)