id: E7FE11 gene_symbol: slc7a10b product_type: PROTEIN status: COMPLETE taxon: id: NCBITaxon:7955 label: Danio rerio description: 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. existing_annotations: - term: id: GO:0005886 label: plasma membrane evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: is_active_in supporting_entities: - FB:FBgn0028425 - MGI:MGI:1298205 - MGI:MGI:1347355 - MGI:MGI:1353656 - MGI:MGI:1355323 - MGI:MGI:1858261 - MGI:MGI:1921337 - MGI:MGI:2156159 - PANTHER:PTN000208507 - RGD:619905 - RGD:620639 - SGD:S000003287 - UniProtKB:P45539 - UniProtKB:P82251 - UniProtKB:Q01650 - UniProtKB:Q92536 - UniProtKB:Q9UHI5 - UniProtKB:Q9UM01 - UniProtKB:Q9UPY5 - WB:WBGene00000002 - WB:WBGene00000007 review: summary: Plasma membrane propagated from the heterodimeric amino acid transporter light-chain node PTN000208507. action: ACCEPT 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. supported_by: - reference_id: PMID:10734121 supporting_text: Asc-1 required 4F2hc for its functional expression. - reference_id: file:DANRE/slc7a10a/slc7a10a-bioinformatics/RESULTS.md supporting_text: No copy has lost a known substrate-site, gating or heavy-chain-linking residue. - 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 (ARBA rule). action: ACCEPT reason: Same as the IBA row. supported_by: - reference_id: PMID:10734121 supporting_text: Asc-1 required 4F2hc for its functional expression. - term: id: GO:0015175 label: neutral L-amino acid transmembrane transporter activity evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables supporting_entities: - MGI:MGI:1355323 - MGI:MGI:1858261 - PANTHER:PTN001369926 - UniProtKB:Q01650 - UniProtKB:Q9NS82 - UniProtKB:Q9UHI5 review: summary: Neutral L-amino acid transporter activity from node PTN001369926 (human SLC7A10, SLC7A5, SLC7A8). action: ACCEPT 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. supported_by: - reference_id: PMID:10734121 supporting_text: 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. - reference_id: file:DANRE/slc7a10a/slc7a10a-bioinformatics/RESULTS.md supporting_text: No copy has lost a known substrate-site, gating or heavy-chain-linking residue. - term: id: GO:0015179 label: L-amino acid transmembrane transporter activity evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: enables supporting_entities: - MGI:MGI:1298205 - MGI:MGI:1355323 - PANTHER:PTN000208507 - SGD:S000001028 - SGD:S000003287 - UniProtKB:P82251 - UniProtKB:Q01650 - UniProtKB:Q92536 - UniProtKB:Q9UHI5 - UniProtKB:Q9UPY5 review: summary: L-amino acid transporter activity from the light-chain node PTN000208507. action: ACCEPT 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. supported_by: - reference_id: PMID:10734121 supporting_text: 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. - term: id: GO:0016020 label: membrane evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: located_in supporting_entities: - InterPro:IPR002293 review: summary: Membrane from the amino acid permease InterPro entry. action: ACCEPT reason: Correct but general; plasma membrane is the specific location. supported_by: - reference_id: file:DANRE/slc7a10a/slc7a10a-bioinformatics/RESULTS.md supporting_text: both have 12 predicted transmembrane helices (UniProt). - term: id: GO:0022857 label: transmembrane transporter activity evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: enables supporting_entities: - InterPro:IPR002293 review: summary: Transmembrane transporter activity from IPR002293. action: ACCEPT reason: Correct but very general; the IBA rows give the specific neutral amino acid activity. supported_by: - reference_id: PMID:10734121 supporting_text: 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. - term: id: GO:0042941 label: D-alanine transmembrane transport evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in supporting_entities: - MGI:MGI:1858261 - PANTHER:PTN002623424 review: summary: D-alanine transmembrane transport from the Asc-1 node PTN002623424. action: ACCEPT 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. supported_by: - reference_id: PMID:10734121 supporting_text: 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. - term: id: GO:0042942 label: D-serine transmembrane transport evidence_type: IBA original_reference_id: GO_REF:0000033 qualifier: involved_in supporting_entities: - MGI:MGI:1858261 - PANTHER:PTN002623424 review: summary: D-serine transmembrane transport from the Asc-1 node PTN002623424. action: ACCEPT 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. supported_by: - reference_id: PMID:10734121 supporting_text: 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. - reference_id: PMID:38589439 supporting_text: 'Middle: Asc-1 adopts an inward open conformation with D-Ser bound in the center of the substrate binding pocket.' - term: id: GO:0055085 label: transmembrane transport evidence_type: IEA original_reference_id: GO_REF:0000002 qualifier: involved_in supporting_entities: - InterPro:IPR002293 review: summary: Transmembrane transport from IPR002293. action: ACCEPT reason: Correct but general. supported_by: - reference_id: PMID:10734121 supporting_text: Asc-1-mediated transport was not dependent on the presence of Na(+) or Cl(-). - term: id: GO:0097009 label: energy homeostasis evidence_type: IMP original_reference_id: PMID:33408126 qualifier: acts_upstream_of_or_within supporting_entities: - ZFIN:ZDB-GENO-211028-10 review: 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. action: KEEP_AS_NON_CORE 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.' supported_by: - reference_id: PMID:33408126 supporting_text: Concordantly, loss of Slc7a10 function in zebrafish in vivo accelerates diet-induced body weight gain and adipocyte enlargement. - reference_id: PMID:36172277 supporting_text: Compared to wildtypes, the fish with impaired Slc7a10b function gained 38% more body weight and had on average 49% larger visceral adipocytes - reference_id: PMID:36172277 supporting_text: Because two isoforms of Slc7a10 exist in zebrafish (Slc7a10a as well as Slc7a10b), this model should be considered a partial global knockout of Slc7a10. - reference_id: PMID:33408126 supporting_text: Mechanistically, SLC7A10 inhibition in human and murine adipocytes decreases adipocyte serine uptake and total glutathione levels and promotes reactive oxygen species (ROS) generation. - term: id: GO:1902475 label: L-alpha-amino acid transmembrane transport evidence_type: IEA original_reference_id: GO_REF:0000108 qualifier: involved_in supporting_entities: - GO:0015179 review: summary: L-alpha-amino acid transmembrane transport inferred from the L-amino acid transporter activity. action: ACCEPT reason: Follows from the accepted activity. supported_by: - reference_id: PMID:25755256 supporting_text: 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. references: - id: GO_REF:0000002 title: Gene Ontology annotation through association of InterPro records with GO terms findings: [] - id: GO_REF:0000033 title: Annotation inferences using phylogenetic trees 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:0000108 title: Automatic assignment of GO terms using logical inference, based on on inter-ontology links findings: [] - id: PMID:33408126 title: Role of the Neutral Amino Acid Transporter SLC7A10 in Adipocyte Lipid Storage, Obesity, and Insulin Resistance. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: 'Abstract only; human/mouse adipocyte SLC7A10 and a zebrafish slc7a10b loss-of-function line (overfeeding: more weight gain, larger visceral adipocytes).' - id: PMID:10734121 title: Identification and characterization of a Na(+)-independent neutral amino acid transporter that associates with the 4F2 heavy chain and exhibits substrate selectivity for small neutral D- and L-amino acids. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Abstract only; cloning and characterization of mouse Asc-1 (substrates, 4F2hc dependence, exchange). - id: PMID:38589439 title: Cryo-EM structure of the human Asc-1 transporter complex. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Full text; human Asc-1-4F2hc structures with D-Ser and L-Ala; mutagenesis of pocket and gate residues; Cys154 disulfide. - id: PMID:25755256 title: The alanine-serine-cysteine-1 (Asc-1) transporter controls glycine levels in the brain and is required for glycinergic inhibitory transmission. findings: [] reference_review: relevance: MEDIUM correctness: VERIFIED review_notes: Mouse knockout; glycine/L-serine transport and brain glycine levels. - id: PMID:34338990 title: 'The zebrafish cationic amino acid transporter/glycoprotein-associated family: sequence and spatiotemporal distribution during development of the transport system b(0,+) (slc3a1/slc7a9).' findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: Catalogue of zebrafish SLC7 genes; lists slc7a10a (chr 7) with adult EST profile heart > kidney > brain > eye and slc7a10b (chr 25) with no data. - id: PMID:36172277 title: The neutral amino acid transporter SLC7A10 in adipose tissue, obesity and insulin resistance. findings: [] reference_review: relevance: HIGH correctness: VERIFIED review_notes: Full-text review by the same group; describes the zebrafish slc7a10b model, why slc7a10b was chosen, and that it is a partial knockout. - id: PMID:35805100 title: Molecular and Cellular Analysis of the Repair of Zebrafish Optic Tectum Meninges Following Laser Injury. findings: [] reference_review: relevance: LOW correctness: VERIFIED review_notes: Full text; scRNA-seq of zebrafish meninges lists SLC7A10B among transporters enriched in arachnoid (ARA) cells. - id: file:DANRE/slc7a10a/slc7a10a-bioinformatics/RESULTS.md title: slc7a10a / slc7a10b protein, expression and synteny comparison reference_review: relevance: HIGH correctness: VERIFIED review_notes: Manual audit verified the sidecar supports both Asc-1 duplicates retaining known substrate-site, gating and heavy-chain-linking residues; the expression differences are public transcript evidence, not direct transport assays. findings: [] core_functions: - description: Light subunit of an Asc-1-type heterodimeric amino acid transporter (predicted to pair with a 4F2hc/slc3a2 heavy chain) that exchanges small neutral L- and D-amino acids (glycine, L-alanine, L-serine, D-serine) across the plasma membrane. All tested Asc-1 functional residues are conserved; the activity is inferred from orthology, not measured for the zebrafish protein. molecular_function: id: GO:0015175 label: neutral L-amino acid transmembrane transporter activity directly_involved_in: - id: GO:0042942 label: D-serine transmembrane transport locations: - id: GO:0005886 label: plasma membrane supported_by: - reference_id: PMID:10734121 supporting_text: 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. - reference_id: PMID:38589439 supporting_text: The HAT-specific disulfide bond is found between Cys154 of Asc-1 and Cys211 of 4F2hc - reference_id: file:DANRE/slc7a10a/slc7a10a-bioinformatics/RESULTS.md supporting_text: No copy has lost a known substrate-site, gating or heavy-chain-linking residue. suggested_questions: - question: 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? - question: Is slc7a10b transcriptionally upregulated or slc7a10a compensating in the slc7a10b mutant line? - question: Does slc7a10b, like gar SLC7A10, keep the ancestral neural (brain, eye) and gonadal expression, with slc7a10a having gained peripheral tissues? suggested_experiments: - hypothesis: slc7a10a and slc7a10b differ in adipose expression and contribute unequally to lipid storage. description: Paralog-specific HCR in situ or qPCR in sorted zebrafish adipocytes; overfeeding assay on slc7a10a, slc7a10b and double mutants. experiment_type: knockout phenotyping - hypothesis: Slc7a10b is an Asc-type exchanger with the same substrate profile as mammalian Asc-1. description: 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. experiment_type: transport assay