{"gene":"SLA","run_date":"2026-06-10T07:46:32","timeline":{"discoveries":[{"year":1998,"finding":"The human SLA (hSLAP) gene was identified as embedded within the largest intron (64-kb) of the thyroglobulin gene on chromosome 8q24, encoding a 276 amino acid protein with SH3 and SH2 domains but lacking a catalytic tyrosine kinase domain. It is transcribed in the opposite direction to thyroglobulin. The highest expression was detected in fetal brain and lung. Two alternatively spliced isoforms were identified.","method":"Exon trapping, cDNA cloning from fetal brain library, Northern blot, sequence analysis","journal":"European journal of biochemistry","confidence":"Medium","confidence_rationale":"Tier 2 / Moderate — cDNA cloning with expression characterization and sequence analysis in a single study; no functional mechanistic experiments performed beyond structural characterization","pmids":["9660183"],"is_preprint":false},{"year":1995,"finding":"The mouse Slap gene was mapped by linkage analysis to mouse chromosome 15, and its putative human homolog SLA was mapped to human chromosome 8q22.3-qter using somatic cell hybrid panels. SLA/SLAP was characterized as an adaptor protein containing SH3 and SH2 domains homologous to Src family kinases but lacking a tyrosine kinase catalytic domain, and shown to bind activated Eck receptor protein-tyrosine kinase.","method":"Linkage analysis, somatic cell hybrid panel mapping","journal":"Genomics","confidence":"Low","confidence_rationale":"Tier 3 / Weak — chromosomal localization only; binding to Eck receptor described by reference to prior work, not directly demonstrated in this paper","pmids":["8825655"],"is_preprint":false},{"year":2009,"finding":"Overexpression and knockdown of SLA in acute lymphoblastic leukemia (ALL) cell lines showed that SLA alone had no effect on cell survival, cell cycle progression, or sensitivity to glucocorticoid (GC)-induced apoptosis, despite SLA being a prominent glucocorticoid response gene. SLA does not contribute to the anti-leukemic effects of glucocorticoids in this context.","method":"Overexpression and siRNA knockdown in ALL cell lines, cell viability assays, cell cycle analysis, apoptosis assays","journal":"Leukemia research","confidence":"Medium","confidence_rationale":"Tier 2 / Weak — loss-of-function and gain-of-function experiments with defined cellular readouts in a single lab; finding is a negative result (SLA does not contribute to GC-induced apoptosis)","pmids":["19631983"],"is_preprint":false}],"current_model":"Human SLA (hSLAP) is a Src-like adaptor protein encoded within an intron of the thyroglobulin gene on chromosome 8q24, containing SH3 and SH2 domains but lacking a kinase catalytic domain; it is transcriptionally induced by glucocorticoids in lymphoid cells but experimental loss- and gain-of-function studies show it does not contribute to glucocorticoid-induced apoptosis in acute lymphoblastic leukemia, leaving its precise mechanistic role in receptor signaling inhibition largely uncharacterized from the available literature."},"narrative":{"mechanistic_narrative":"SLA (hSLAP) is a Src-like adaptor protein that contains SH3 and SH2 domains but lacks a tyrosine kinase catalytic domain, structurally resembling Src family kinases while acting as an adaptor rather than an enzyme [PMID:9660183]. The gene is embedded within the largest intron of the thyroglobulin gene on chromosome 8q24 and is transcribed in the opposite orientation, with highest expression detected in fetal brain and lung and two alternatively spliced isoforms [PMID:9660183]. In acute lymphoblastic leukemia cells, SLA is a prominent glucocorticoid response gene, but neither its overexpression nor its knockdown alters cell survival, cell cycle progression, or sensitivity to glucocorticoid-induced apoptosis, indicating it does not mediate the anti-leukemic effects of glucocorticoids in this context [PMID:19631983]. Beyond its domain architecture and this negative functional result, the receptor-signaling role of SLA is largely uncharacterized in the available corpus.","teleology":[{"year":1995,"claim":"Establishing where SLA lies in the genome and that it is an adaptor rather than a kinase framed it as a potential modulator of receptor tyrosine kinase signaling.","evidence":"Linkage analysis and somatic cell hybrid panel mapping placing mouse Slap on chromosome 15 and human SLA on 8q22.3-qter, with domain characterization","pmids":["8825655"],"confidence":"Low","gaps":["Eck receptor binding was cited from prior work, not directly demonstrated here","no functional consequence of the adaptor–receptor interaction tested","mapping resolution did not define the precise locus relationship later refined"]},{"year":1998,"claim":"Cloning the human gene defined its protein product, isoforms, and unusual genomic embedding, providing the molecular foundation for any mechanistic study.","evidence":"Exon trapping, cDNA cloning from a fetal brain library, Northern blot, and sequence analysis","pmids":["9660183"],"confidence":"Medium","gaps":["no mechanistic or interaction experiments performed","functional significance of the two splice isoforms unknown","biological role of fetal brain/lung enrichment not addressed"]},{"year":2009,"claim":"Testing whether SLA, a strong glucocorticoid-induced transcript, drives steroid-induced leukemic cell death resolved a candidate mechanism by ruling it out.","evidence":"Overexpression and siRNA knockdown in ALL cell lines with viability, cell cycle, and apoptosis readouts","pmids":["19631983"],"confidence":"Medium","gaps":["negative result does not exclude roles in other cell types or signaling contexts","direct molecular targets or partners of SLA not identified","reason for its strong glucocorticoid induction left unexplained"]},{"year":null,"claim":"The direct molecular function of SLA — which receptors or substrates it engages through its SH3/SH2 domains and what downstream signaling it modulates — remains undefined in the available corpus.","evidence":"","pmids":[],"confidence":"Low","gaps":["no validated physical partner demonstrated in human cells","no signaling pathway directly attributed to SLA","physiological function in fetal brain/lung uncharacterized"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0060090","term_label":"molecular adaptor activity","supporting_discovery_ids":[0]}],"localization":[],"pathway":[],"complexes":[],"partners":[],"other_free_text":[]}},"prefetch_data":{"uniprot":{"accession":"Q13239","full_name":"Src-like-adapter","aliases":["Src-like-adapter protein 1","SLAP-1","hSLAP"],"length_aa":276,"mass_kda":31.2,"function":"Adapter protein, which negatively regulates T-cell receptor (TCR) signaling. Inhibits T-cell antigen-receptor induced activation of nuclear factor of activated T-cells. Involved in the negative regulation of positive selection and mitosis of T-cells. May act by linking signaling proteins such as ZAP70 with CBL, leading to a CBL dependent degradation of signaling proteins","subcellular_location":"Cytoplasm; Endosome","url":"https://www.uniprot.org/uniprotkb/Q13239/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/SLA","classification":"Not Classified","n_dependent_lines":0,"n_total_lines":1208,"dependency_fraction":0.0},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[],"url":"https://opencell.sf.czbiohub.org/search/SLA","total_profiled":1310},"omim":[{"mim_id":"619597","title":"tRNA SELENOCYSTEINE 1-ASSOCIATED PROTEIN 1; TRNAU1AP","url":"https://www.omim.org/entry/619597"},{"mim_id":"617440","title":"PAPILLARY THYROID CARCINOMA SUSCEPTIBILITY CANDIDATE 1 GENE; PTCSC1","url":"https://www.omim.org/entry/617440"},{"mim_id":"613009","title":"O-PHOSPHOSERINE tRNA-SELENOCYSTEINE tRNA SYNTHASE; SEPSECS","url":"https://www.omim.org/entry/613009"},{"mim_id":"606577","title":"SRC-LIKE ADAPTOR 2; SLA2","url":"https://www.omim.org/entry/606577"},{"mim_id":"601099","title":"SRC-LIKE ADAPTOR; SLA","url":"https://www.omim.org/entry/601099"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Nuclear membrane","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"}],"tissue_specificity":"Group enriched","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"bone marrow","ntpm":92.1},{"tissue":"lymphoid tissue","ntpm":145.7}],"url":"https://www.proteinatlas.org/search/SLA"},"hgnc":{"alias_symbol":["SLA1","SLAP-1","hSLAP","SLAP"],"prev_symbol":[]},"alphafold":{"accession":"Q13239","domains":[{"cath_id":"2.30.30.40","chopping":"22-81","consensus_level":"medium","plddt":89.8262,"start":22,"end":81},{"cath_id":"3.30.505.10","chopping":"83-180","consensus_level":"medium","plddt":90.2857,"start":83,"end":180}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q13239","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q13239-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q13239-F1-predicted_aligned_error_v6.png","plddt_mean":74.44},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=SLA","jax_strain_url":"https://www.jax.org/strain/search?query=SLA"},"sequence":{"accession":"Q13239","fasta_url":"https://rest.uniprot.org/uniprotkb/Q13239.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q13239/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q13239"}},"corpus_meta":[{"pmid":"9988272","id":"PMC_9988272","title":"Hephaestin, a ceruloplasmin homologue implicated in intestinal iron transport, is defective in the sla mouse.","date":"1999","source":"Nature genetics","url":"https://pubmed.ncbi.nlm.nih.gov/9988272","citation_count":825,"is_preprint":false},{"pmid":"11952734","id":"PMC_11952734","title":"The use of reduced healing times on ITI implants with a sandblasted and acid-etched (SLA) surface: early results from clinical trials on ITI SLA implants.","date":"2002","source":"Clinical oral implants research","url":"https://pubmed.ncbi.nlm.nih.gov/11952734","citation_count":430,"is_preprint":false},{"pmid":"8335689","id":"PMC_8335689","title":"Synthetic-lethal interactions identify two novel genes, SLA1 and SLA2, that control membrane cytoskeleton assembly in Saccharomyces cerevisiae.","date":"1993","source":"The Journal of cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/8335689","citation_count":261,"is_preprint":false},{"pmid":"10801173","id":"PMC_10801173","title":"Identification of target antigen for SLA/LP autoantibodies in autoimmune hepatitis.","date":"2000","source":"Lancet (London, England)","url":"https://pubmed.ncbi.nlm.nih.gov/10801173","citation_count":223,"is_preprint":false},{"pmid":"28114170","id":"PMC_28114170","title":"Humoral Reactivity of Renal Transplant-Waitlisted Patients to Cells From GGTA1/CMAH/B4GalNT2, and SLA Class I Knockout Pigs.","date":"2017","source":"Transplantation","url":"https://pubmed.ncbi.nlm.nih.gov/28114170","citation_count":191,"is_preprint":false},{"pmid":"18760302","id":"PMC_18760302","title":"Molecular genetics of the swine major histocompatibility complex, the SLA complex.","date":"2008","source":"Developmental and comparative immunology","url":"https://pubmed.ncbi.nlm.nih.gov/18760302","citation_count":147,"is_preprint":false},{"pmid":"12117891","id":"PMC_12117891","title":"Establishment of standardised SLA/LP immunoassays: specificity for autoimmune hepatitis, worldwide occurrence, and clinical characteristics.","date":"2002","source":"Gut","url":"https://pubmed.ncbi.nlm.nih.gov/12117891","citation_count":122,"is_preprint":false},{"pmid":"10471702","id":"PMC_10471702","title":"Genetic study of interactions between the cytoskeletal assembly protein sla1 and prion-forming domain of the release factor Sup35 (eRF3) in Saccharomyces cerevisiae.","date":"1999","source":"Genetics","url":"https://pubmed.ncbi.nlm.nih.gov/10471702","citation_count":106,"is_preprint":false},{"pmid":"7912457","id":"PMC_7912457","title":"Evidence that activation of human T cells by porcine endothelium involves direct recognition of porcine SLA and costimulation by porcine ligands for LFA-1 and CD2.","date":"1994","source":"Transplantation","url":"https://pubmed.ncbi.nlm.nih.gov/7912457","citation_count":96,"is_preprint":false},{"pmid":"22941963","id":"PMC_22941963","title":"The roles of PI3K/Akt signaling pathway in regulating MC3T3-E1 preosteoblast proliferation and differentiation on SLA and SLActive titanium surfaces.","date":"2012","source":"Journal of biomedical materials research. 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Part A","url":"https://pubmed.ncbi.nlm.nih.gov/26418567","citation_count":19,"is_preprint":false},{"pmid":"34835070","id":"PMC_34835070","title":"Evaluation of Cellular Immunity with ASFV Infection by Swine Leukocyte Antigen (SLA)-Peptide Tetramers.","date":"2021","source":"Viruses","url":"https://pubmed.ncbi.nlm.nih.gov/34835070","citation_count":18,"is_preprint":false},{"pmid":"27150838","id":"PMC_27150838","title":"SLA-PGN-primed dendritic cell-based vaccination induces Th17-mediated protective immunity against experimental visceral leishmaniasis: a crucial role of PKCβ.","date":"2016","source":"Pathogens and disease","url":"https://pubmed.ncbi.nlm.nih.gov/27150838","citation_count":18,"is_preprint":false},{"pmid":"3141620","id":"PMC_3141620","title":"Influence of SLA haplotype on preimplantation embryonic cell number in miniature pigs.","date":"1988","source":"Journal of reproduction and fertility","url":"https://pubmed.ncbi.nlm.nih.gov/3141620","citation_count":18,"is_preprint":false},{"pmid":"22984928","id":"PMC_22984928","title":"Identification of peptides from foot-and-mouth disease virus structural proteins bound by class I swine leukocyte antigen (SLA) alleles, SLA-1*0401 and SLA-2*0401.","date":"2012","source":"Animal genetics","url":"https://pubmed.ncbi.nlm.nih.gov/22984928","citation_count":17,"is_preprint":false},{"pmid":"19631983","id":"PMC_19631983","title":"Functional analyses of Src-like adaptor (SLA), a glucocorticoid-regulated gene in acute lymphoblastic leukemia.","date":"2009","source":"Leukemia research","url":"https://pubmed.ncbi.nlm.nih.gov/19631983","citation_count":17,"is_preprint":false},{"pmid":"29222521","id":"PMC_29222521","title":"Cytokines and chemokines measured in dried SLA-stimulated whole blood spots for asymptomatic Leishmania infantum and Leishmania donovani infection.","date":"2017","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/29222521","citation_count":17,"is_preprint":false},{"pmid":"23137324","id":"PMC_23137324","title":"Comprehensive and high-resolution typing of swine leukocyte antigen DQA from genomic DNA and determination of 25 new SLA class II haplotypes.","date":"2012","source":"Tissue antigens","url":"https://pubmed.ncbi.nlm.nih.gov/23137324","citation_count":17,"is_preprint":false},{"pmid":"2515776","id":"PMC_2515776","title":"Genetic and other effects on bacterial phagocytosis and killing by cultured peripheral blood monocytes of SLA-defined miniature pigs.","date":"1989","source":"Animal genetics","url":"https://pubmed.ncbi.nlm.nih.gov/2515776","citation_count":17,"is_preprint":false},{"pmid":"11943330","id":"PMC_11943330","title":"Development of a rapid in vitro protein refolding assay which discriminates between peptide-bound and peptide-free forms of recombinant porcine major histocompatibility class I complex (SLA-I).","date":"2002","source":"Veterinary immunology and immunopathology","url":"https://pubmed.ncbi.nlm.nih.gov/11943330","citation_count":17,"is_preprint":false},{"pmid":"29326671","id":"PMC_29326671","title":"Specificity Characterization of SLA Class I Molecules Binding to Swine-Origin Viral Cytotoxic T Lymphocyte Epitope Peptides in Vitro.","date":"2017","source":"Frontiers in microbiology","url":"https://pubmed.ncbi.nlm.nih.gov/29326671","citation_count":17,"is_preprint":false},{"pmid":"6177778","id":"PMC_6177778","title":"Transplantation in miniature swine. XII. N-terminal sequences of class I histocompatibility antigens (SLA) and beta 2-microglobulin.","date":"1982","source":"Journal of immunology (Baltimore, Md. : 1950)","url":"https://pubmed.ncbi.nlm.nih.gov/6177778","citation_count":17,"is_preprint":false},{"pmid":"20604896","id":"PMC_20604896","title":"Simple and comprehensive SLA-DQB1 genotyping using genomic PCR and direct sequencing.","date":"2010","source":"Tissue antigens","url":"https://pubmed.ncbi.nlm.nih.gov/20604896","citation_count":16,"is_preprint":false},{"pmid":"31959823","id":"PMC_31959823","title":"SLA-1 Genetic Diversity in Pigs: Extensive Analysis of Copy Number Variation, Heterozygosity, Expression, and Breed Specificity.","date":"2020","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/31959823","citation_count":16,"is_preprint":false},{"pmid":"15118849","id":"PMC_15118849","title":"Sequence and mRNA expression of nonclassical SLA class I genes SLA-7 and SLA-8.","date":"2004","source":"Immunogenetics","url":"https://pubmed.ncbi.nlm.nih.gov/15118849","citation_count":16,"is_preprint":false},{"pmid":"36868181","id":"PMC_36868181","title":"Osteogenic and anti-inflammatory effects of SLA titanium substrates doped with chitosan-stabilized selenium nanoparticles via a covalent coupling strategy.","date":"2023","source":"Colloids and surfaces. B, Biointerfaces","url":"https://pubmed.ncbi.nlm.nih.gov/36868181","citation_count":16,"is_preprint":false},{"pmid":"31969884","id":"PMC_31969884","title":"Illumination of PRRSV Cytotoxic T Lymphocyte Epitopes by the Three-Dimensional Structure and Peptidome of Swine Lymphocyte Antigen Class I (SLA-I).","date":"2020","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/31969884","citation_count":16,"is_preprint":false},{"pmid":"1683187","id":"PMC_1683187","title":"Marked genetic polymorphism of the swine steroid 21-hydroxylase gene, and its location between the SLA class I and class II regions.","date":"1991","source":"Animal genetics","url":"https://pubmed.ncbi.nlm.nih.gov/1683187","citation_count":16,"is_preprint":false},{"pmid":"27693332","id":"PMC_27693332","title":"Lymphoproliferative response after stimulation with soluble leishmania antigen (SLA) as a predictor of visceral leishmaniasis (VL) relapse in HIV+ patients.","date":"2016","source":"Acta tropica","url":"https://pubmed.ncbi.nlm.nih.gov/27693332","citation_count":16,"is_preprint":false},{"pmid":"22825870","id":"PMC_22825870","title":"Role of Scd5, a protein phosphatase-1 targeting protein, in phosphoregulation of Sla1 during endocytosis.","date":"2012","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/22825870","citation_count":15,"is_preprint":false},{"pmid":"20623998","id":"PMC_20623998","title":"Human SepSecS or SLA/LP: selenocysteine formation and autoimmune hepatitis.","date":"2010","source":"Biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/20623998","citation_count":15,"is_preprint":false},{"pmid":"14745200","id":"PMC_14745200","title":"Truncated Sla1 induces haploid meiosis through the Pat1-Mei2 system in fission yeast.","date":"2004","source":"Bioscience, biotechnology, and biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/14745200","citation_count":15,"is_preprint":false},{"pmid":"37604847","id":"PMC_37604847","title":"The non-classical major histocompatibility complex II protein SLA-DM is crucial for African swine fever virus replication.","date":"2023","source":"Scientific reports","url":"https://pubmed.ncbi.nlm.nih.gov/37604847","citation_count":15,"is_preprint":false},{"pmid":"9504898","id":"PMC_9504898","title":"Antibodies to P450IID6, SLA, PDH-E2 and BCKD-E2 in Japanese patients with chronic hepatitis.","date":"1997","source":"Journal of gastroenterology and hepatology","url":"https://pubmed.ncbi.nlm.nih.gov/9504898","citation_count":14,"is_preprint":false},{"pmid":"26382972","id":"PMC_26382972","title":"Improved osseointegration of long-term stored SLA implant by hydrothermal sterilization.","date":"2015","source":"Journal of the mechanical behavior of biomedical materials","url":"https://pubmed.ncbi.nlm.nih.gov/26382972","citation_count":14,"is_preprint":false},{"pmid":"22213622","id":"PMC_22213622","title":"Evaluation of chemically modified SLA implants (modSLA) biofunctionalized with integrin (RGD)- and heparin (KRSR)-binding peptides.","date":"2011","source":"Journal of biomedical materials research. Part A","url":"https://pubmed.ncbi.nlm.nih.gov/22213622","citation_count":14,"is_preprint":false},{"pmid":"29542219","id":"PMC_29542219","title":"The Sla1 adaptor-clathrin interaction regulates coat formation and progression of endocytosis.","date":"2018","source":"Traffic (Copenhagen, Denmark)","url":"https://pubmed.ncbi.nlm.nih.gov/29542219","citation_count":13,"is_preprint":false},{"pmid":"23575112","id":"PMC_23575112","title":"Structural mimicry between SLA/LP and Rickettsia surface antigens as a driver of autoimmune hepatitis: insights from an in silico study.","date":"2013","source":"Theoretical biology & medical modelling","url":"https://pubmed.ncbi.nlm.nih.gov/23575112","citation_count":13,"is_preprint":false},{"pmid":"26634489","id":"PMC_26634489","title":"Swine leukocyte antigen class II genes (SLA-DRA, SLA-DRB1, SLA-DQA, SLA-DQB1) polymorphism and genotyping in Guizhou minipigs.","date":"2015","source":"Genetics and molecular research : GMR","url":"https://pubmed.ncbi.nlm.nih.gov/26634489","citation_count":12,"is_preprint":false},{"pmid":"23139801","id":"PMC_23139801","title":"Prediction of altered 3'- UTR miRNA-binding sites from RNA-Seq data: the swine leukocyte antigen complex (SLA) as a model region.","date":"2012","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23139801","citation_count":12,"is_preprint":false},{"pmid":"33195147","id":"PMC_33195147","title":"Human Salivary Histatin-1 Promotes Osteogenic Cell Spreading on Both Bio-Inert Substrates and Titanium SLA Surfaces.","date":"2020","source":"Frontiers in bioengineering and biotechnology","url":"https://pubmed.ncbi.nlm.nih.gov/33195147","citation_count":11,"is_preprint":false},{"pmid":"34858400","id":"PMC_34858400","title":"Porcine Epidemic Diarrhea Virus Envelope Protein Blocks SLA-DR Expression in Barrow-Derived Dendritic Cells by Inhibiting Promoters Activation.","date":"2021","source":"Frontiers in immunology","url":"https://pubmed.ncbi.nlm.nih.gov/34858400","citation_count":11,"is_preprint":false},{"pmid":"32911818","id":"PMC_32911818","title":"Association of Porcine Swine Leukocyte Antigen (SLA) Haplotypes with B- and T-Cell Immune Response to Foot-and-Mouth Disease Virus (FMDV) Peptides.","date":"2020","source":"Vaccines","url":"https://pubmed.ncbi.nlm.nih.gov/32911818","citation_count":11,"is_preprint":false},{"pmid":"38394240","id":"PMC_38394240","title":"A neural pathway for social modulation of spontaneous locomotor activity (SoMo-SLA) in Drosophila.","date":"2024","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/38394240","citation_count":11,"is_preprint":false},{"pmid":"15935298","id":"PMC_15935298","title":"Novel SLA-DQ alleles and their recombinant molecules in xenogeneic stimulation of human T cells.","date":"2005","source":"Transplant immunology","url":"https://pubmed.ncbi.nlm.nih.gov/15935298","citation_count":11,"is_preprint":false},{"pmid":"15780067","id":"PMC_15780067","title":"Anti-tRNP(ser)sec/SLA/LP autoantibodies. Comparative study using in-house ELISA with a recombinant 48.8 kDa protein, immunoblot, and analysis of immunoprecipitated RNAs.","date":"2005","source":"Liver international : official journal of the International Association for the Study of the Liver","url":"https://pubmed.ncbi.nlm.nih.gov/15780067","citation_count":11,"is_preprint":false},{"pmid":"27881639","id":"PMC_27881639","title":"Enhancement of osseointegration by direct coating of rhBMP-2 on target-ion induced plasma sputtering treated SLA surface for dental application.","date":"2016","source":"Journal of biomaterials applications","url":"https://pubmed.ncbi.nlm.nih.gov/27881639","citation_count":11,"is_preprint":false},{"pmid":"35497867","id":"PMC_35497867","title":"Biocorrosion of pure and SLA titanium surfaces in the presence of Porphyromonas gingivalis and its effects on osteoblast behavior.","date":"2020","source":"RSC advances","url":"https://pubmed.ncbi.nlm.nih.gov/35497867","citation_count":10,"is_preprint":false},{"pmid":"35424597","id":"PMC_35424597","title":"Antimicrobial peptide GL13K immobilized onto SLA-treated titanium by silanization: antibacterial effect against methicillin-resistant Staphylococcus aureus (MRSA).","date":"2022","source":"RSC advances","url":"https://pubmed.ncbi.nlm.nih.gov/35424597","citation_count":10,"is_preprint":false},{"pmid":"8825655","id":"PMC_8825655","title":"Chromosomal localization of the mouse Src-like adapter protein (Slap) gene and its putative human homolog SLA.","date":"1995","source":"Genomics","url":"https://pubmed.ncbi.nlm.nih.gov/8825655","citation_count":10,"is_preprint":false},{"pmid":"11214013","id":"PMC_11214013","title":"Influence of glutaraldehyde fixation on the detection of SLA-I and II antigens and calcification tendency in porcine cardiac tissue.","date":"2000","source":"Scandinavian cardiovascular journal : SCJ","url":"https://pubmed.ncbi.nlm.nih.gov/11214013","citation_count":10,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":51635,"output_tokens":1324,"usd":0.087383,"stage1_stop_reason":"end_turn"},"stage2":{"model":"claude-opus-4-8","input_tokens":7389,"output_tokens":1353,"usd":0.035385,"stage2_stop_reason":"end_turn"},"total_usd":0.122768,"stage1_batch_id":"msgbatch_013LWZZT6MWaqB9qyTSeQBmU","stage2_batch_id":"msgbatch_0194ZzQaTGNpruoNJBbEMbt3","note":"batch pricing = 50% of standard"},"stage1_raw":"Looking through the abstracts, I need to identify papers about the canonical human/mammalian SLA gene (HGNC: SLA, also known as SLA1, SLAP-1, hSLAP) - a Src-like adaptor protein involved in T-cell/B-cell receptor signaling.\n\nPapers about the canonical SLA protein:\n- PMID 9660183: Describes cloning of hSLAP (human Src-like adaptor protein), the human ortholog of murine SLAP\n- PMID 8825655: Chromosomal localization of mouse Slap and human SLA\n- PMID 19631983: Functional analyses of SLA in acute lymphoblastic leukemia\n\nPapers about yeast SLA1 (Saccharomyces cerevisiae) - need to assess if ortholog: The yeast SLA1 is a different protein (multi-SH3 domain endocytic adaptor), NOT an ortholog of human SLA/SLAP. Human SLA/SLAP is a Src-like adaptor with SH3+SH2 domains but no kinase domain. These are distinct proteins despite the name overlap.\n\nPapers about S. pombe Sla1 (PMID 14665462, 14745200) - also a different protein (La homolog).\n\nPapers about SLA/LP autoantigen in autoimmune hepatitis - this is a different protein (SepSecS/tRNP(Ser)Sec).\n\nPapers about swine SLA (swine leukocyte antigen) - completely different (MHC complex).\n\nPapers about trypanosome SLA1 - different organism, different protein.\n\nSo the relevant papers for the canonical human SLA gene are: PMID 9660183, PMID 8825655, and PMID 19631983.\n\n```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 1998,\n      \"finding\": \"The human SLA (hSLAP) gene was identified as embedded within the largest intron (64-kb) of the thyroglobulin gene on chromosome 8q24, encoding a 276 amino acid protein with SH3 and SH2 domains but lacking a catalytic tyrosine kinase domain. It is transcribed in the opposite direction to thyroglobulin. The highest expression was detected in fetal brain and lung. Two alternatively spliced isoforms were identified.\",\n      \"method\": \"Exon trapping, cDNA cloning from fetal brain library, Northern blot, sequence analysis\",\n      \"journal\": \"European journal of biochemistry\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Moderate — cDNA cloning with expression characterization and sequence analysis in a single study; no functional mechanistic experiments performed beyond structural characterization\",\n      \"pmids\": [\"9660183\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 1995,\n      \"finding\": \"The mouse Slap gene was mapped by linkage analysis to mouse chromosome 15, and its putative human homolog SLA was mapped to human chromosome 8q22.3-qter using somatic cell hybrid panels. SLA/SLAP was characterized as an adaptor protein containing SH3 and SH2 domains homologous to Src family kinases but lacking a tyrosine kinase catalytic domain, and shown to bind activated Eck receptor protein-tyrosine kinase.\",\n      \"method\": \"Linkage analysis, somatic cell hybrid panel mapping\",\n      \"journal\": \"Genomics\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 / Weak — chromosomal localization only; binding to Eck receptor described by reference to prior work, not directly demonstrated in this paper\",\n      \"pmids\": [\"8825655\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2009,\n      \"finding\": \"Overexpression and knockdown of SLA in acute lymphoblastic leukemia (ALL) cell lines showed that SLA alone had no effect on cell survival, cell cycle progression, or sensitivity to glucocorticoid (GC)-induced apoptosis, despite SLA being a prominent glucocorticoid response gene. SLA does not contribute to the anti-leukemic effects of glucocorticoids in this context.\",\n      \"method\": \"Overexpression and siRNA knockdown in ALL cell lines, cell viability assays, cell cycle analysis, apoptosis assays\",\n      \"journal\": \"Leukemia research\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 / Weak — loss-of-function and gain-of-function experiments with defined cellular readouts in a single lab; finding is a negative result (SLA does not contribute to GC-induced apoptosis)\",\n      \"pmids\": [\"19631983\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"Human SLA (hSLAP) is a Src-like adaptor protein encoded within an intron of the thyroglobulin gene on chromosome 8q24, containing SH3 and SH2 domains but lacking a kinase catalytic domain; it is transcriptionally induced by glucocorticoids in lymphoid cells but experimental loss- and gain-of-function studies show it does not contribute to glucocorticoid-induced apoptosis in acute lymphoblastic leukemia, leaving its precise mechanistic role in receptor signaling inhibition largely uncharacterized from the available literature.\"\n}\n```","stage2_raw":"{\n  \"mechanistic_narrative\": \"SLA (hSLAP) is a Src-like adaptor protein that contains SH3 and SH2 domains but lacks a tyrosine kinase catalytic domain, structurally resembling Src family kinases while acting as an adaptor rather than an enzyme [#0]. The gene is embedded within the largest intron of the thyroglobulin gene on chromosome 8q24 and is transcribed in the opposite orientation, with highest expression detected in fetal brain and lung and two alternatively spliced isoforms [#0]. In acute lymphoblastic leukemia cells, SLA is a prominent glucocorticoid response gene, but neither its overexpression nor its knockdown alters cell survival, cell cycle progression, or sensitivity to glucocorticoid-induced apoptosis, indicating it does not mediate the anti-leukemic effects of glucocorticoids in this context [#2]. Beyond its domain architecture and this negative functional result, the receptor-signaling role of SLA is largely uncharacterized in the available corpus.\",\n  \"teleology\": [\n    {\n      \"year\": 1995,\n      \"claim\": \"Establishing where SLA lies in the genome and that it is an adaptor rather than a kinase framed it as a potential modulator of receptor tyrosine kinase signaling.\",\n      \"evidence\": \"Linkage analysis and somatic cell hybrid panel mapping placing mouse Slap on chromosome 15 and human SLA on 8q22.3-qter, with domain characterization\",\n      \"pmids\": [\"8825655\"],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"Eck receptor binding was cited from prior work, not directly demonstrated here\", \"no functional consequence of the adaptor–receptor interaction tested\", \"mapping resolution did not define the precise locus relationship later refined\"]\n    },\n    {\n      \"year\": 1998,\n      \"claim\": \"Cloning the human gene defined its protein product, isoforms, and unusual genomic embedding, providing the molecular foundation for any mechanistic study.\",\n      \"evidence\": \"Exon trapping, cDNA cloning from a fetal brain library, Northern blot, and sequence analysis\",\n      \"pmids\": [\"9660183\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"no mechanistic or interaction experiments performed\", \"functional significance of the two splice isoforms unknown\", \"biological role of fetal brain/lung enrichment not addressed\"]\n    },\n    {\n      \"year\": 2009,\n      \"claim\": \"Testing whether SLA, a strong glucocorticoid-induced transcript, drives steroid-induced leukemic cell death resolved a candidate mechanism by ruling it out.\",\n      \"evidence\": \"Overexpression and siRNA knockdown in ALL cell lines with viability, cell cycle, and apoptosis readouts\",\n      \"pmids\": [\"19631983\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\"negative result does not exclude roles in other cell types or signaling contexts\", \"direct molecular targets or partners of SLA not identified\", \"reason for its strong glucocorticoid induction left unexplained\"]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"The direct molecular function of SLA — which receptors or substrates it engages through its SH3/SH2 domains and what downstream signaling it modulates — remains undefined in the available corpus.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\"no validated physical partner demonstrated in human cells\", \"no signaling pathway directly attributed to SLA\", \"physiological function in fetal brain/lung uncharacterized\"]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0060090\", \"supporting_discovery_ids\": [0]}\n    ],\n    \"localization\": [],\n    \"pathway\": [],\n    \"complexes\": [],\n    \"partners\": [],\n    \"other_free_text\": []\n  }\n}","audit_flag":null,"evaluation":{"pairwise":"loss","faith_supported":3,"faith_total":3,"faith_pct":100.0}}