{"gene":"TTLL5","run_date":"2026-04-28T21:43:00","timeline":{"discoveries":[{"year":2016,"finding":"TTLL5 glutamylates RPGR(ORF15) in its Glu-Gly-rich repetitive region; the RPGR(ORF15) C-terminal basic domain binds the noncatalytic cofactor interaction domain unique to TTLL5 and targets TTLL5 to glutamylate RPGR. Only TTLL5 (not other TTLL family glutamylases) interacts with RPGR(ORF15) in cells. A Ttll5 mutant mouse shows complete loss of RPGR glutamylation without marked changes in tubulin glutamylation, and develops photoreceptor degeneration with mislocalization of cone opsins similar to Rpgr-null mice. TTLL5 disease mutants causing human retinal dystrophy show impaired glutamylation of RPGR(ORF15).","method":"Co-IP, in vivo mutagenesis, Ttll5 mutant mouse model, immunofluorescence, electroretinography","journal":"Proceedings of the National Academy of Sciences of the United States of America","confidence":"High","confidence_rationale":"Tier 1-2 — multiple orthogonal methods (Co-IP, reconstitution in cells, in vivo KO mouse, mutagenesis of disease alleles) in a single rigorous study","pmids":["27162334"],"is_preprint":false},{"year":2013,"finding":"Disruption of the Ttll5/Stamp gene in male mice causes defective α-tubulin polyglutamylation specifically in sperm tails, leading to abnormal axonemal structures with loss of tubulin doublets, reduced progressive sperm motility, and male infertility. The phenotype is tissue-selective (testes express STAMP mRNA 20-fold higher than any other organ) and unrelated to other Ttll genes or 24 genes previously linked to sperm function.","method":"Targeted gene deletion mouse model, electron microscopy of sperm axonemes, α-tubulin polyglutamylation assay, fertility assays, qRT-PCR","journal":"The Journal of biological chemistry","confidence":"High","confidence_rationale":"Tier 2 — clean KO mouse with defined cellular and biochemical phenotype, multiple orthogonal methods","pmids":["23558686"],"is_preprint":false},{"year":2014,"finding":"Biallelic loss-of-function variants in TTLL5, which encodes a tubulin glutamylase, cause cone, cone-rod, and macular dystrophies in humans. In human and murine retinae, TTLL5 localizes to the centrioles at the base of the connecting cilium of photoreceptors, and TTLL5 has been reported to be essential for correct sperm flagella function and to play a role in polyglutamylation of primary cilia in vitro.","method":"Exome sequencing, Sanger sequencing, immunolocalization in retinal sections","journal":"American journal of human genetics","confidence":"Medium","confidence_rationale":"Tier 2-3 — human genetics plus direct immunolocalization; mechanistic link to glutamylation inferred from prior literature cited in paper","pmids":["24791901"],"is_preprint":false},{"year":2016,"finding":"Mutations in TTLL5 delineate an allele-specific syndrome affecting both vision and reproduction: truncating variants cause cone-dominated retinopathy and substantially reduced sperm motility/infertility in male patients, whereas missense variants cause retinopathy without infertility. TTLL5 antibodies stain the basal body of photoreceptor cells in rat retina and the centrosome of the spermatozoon flagellum in humans, indicating a shared polyglutamylase mechanism in these two cell types.","method":"Next-generation sequencing, autozygome screening, immunofluorescence on human/rat tissues, sperm motility assays","journal":"Human molecular genetics","confidence":"Medium","confidence_rationale":"Tier 2-3 — human genetics with direct immunolocalization in two species; functional consequence of truncating vs. missense alleles established","pmids":["28173158"],"is_preprint":false},{"year":2006,"finding":"STAMP (TTLL5) was identified as a novel 1,277-amino-acid endogenous protein that associates with coactivators TIF2 and SRC-1 and is selective for a subset of steroid/nuclear receptors including glucocorticoid receptor (GR). Transfected STAMP increases the effects of TIF2 in GR-mediated gene repression and induction; siRNA knockdown of endogenous STAMP reduces both induction and repression of endogenous GR target genes. Endogenous STAMP colocalizes with GR in intact cells and is recruited to promoters of GR-induced and GR-repressed genes.","method":"Co-IP, siRNA knockdown of endogenous gene, ChIP on endogenous promoters, co-localization by immunofluorescence, reporter gene assays","journal":"Molecular and cellular biology","confidence":"High","confidence_rationale":"Tier 2 — multiple orthogonal methods (Co-IP, ChIP, siRNA with endogenous gene readouts, co-localization) in a single study","pmids":["17116691"],"is_preprint":false},{"year":2012,"finding":"Separate regions of TTLL5/STAMP, coactivator TIF2, and glucocorticoid receptor (GR) independently modify different parameters of GR-mediated gene induction (Amax, EC50, partial agonist activity), demonstrating that these three parameters can be independently regulated by different protein domains within a ternary GR–TIF2–STAMP complex.","method":"Transfection of 25 fragment combinations, reporter gene assays for Amax/EC50/PAA, endogenous gene induction assays","journal":"Molecular and cellular endocrinology","confidence":"Medium","confidence_rationale":"Tier 2 — systematic domain-dissection with multiple functional readouts in a single study","pmids":["22342989"],"is_preprint":false},{"year":2010,"finding":"TTLL5/STAMP overexpression reduces proliferation of HEK293 cells in a steroid-independent manner; siRNA-mediated knockdown of STAMP mRNA alters proliferation of ovarian cancer cell lines in a cell-line-specific fashion, indicating a physiological role for STAMP in regulating cell growth rates independently of steroid hormones.","method":"Stable STAMP overexpression in HEK293 cells, siRNA knockdown, proliferation assays across multiple cancer cell lines","journal":"BMC cancer","confidence":"Low","confidence_rationale":"Tier 3 — single lab, single functional readout (proliferation), no defined molecular pathway for the growth effect","pmids":["20374646"],"is_preprint":false},{"year":2021,"finding":"Novel biallelic variants in TTLL5 cause cone-rod dystrophy and early-onset severe retinal dystrophy; protein modeling of identified variants suggests different effects on protein function, providing a potential basis for genotype-phenotype correlation.","method":"Targeted NGS gene panels, CNV analysis, protein structural modeling, ERG, OCT, autofluorescence imaging","journal":"International journal of molecular sciences","confidence":"Low","confidence_rationale":"Tier 3-4 — mechanistic inference from structural modeling only; clinical genetics study without direct biochemical validation","pmids":["34203883"],"is_preprint":false}],"current_model":"TTLL5 is a tubulin tyrosine ligase-like polyglutamylase that catalyzes polyglutamylation of both α-tubulin (required for sperm axoneme integrity and male fertility) and the photoreceptor-specific protein RPGR(ORF15) (required for photoreceptor function); RPGR(ORF15) is recruited as a substrate via its C-terminal basic domain binding to a noncatalytic cofactor interaction domain unique to TTLL5, and TTLL5 additionally functions as a transcriptional comodulator in glucocorticoid receptor signaling by forming a ternary complex with TIF2/SRC-1 coactivators to tune gene induction and repression parameters."},"narrative":{"teleology":[{"year":2006,"claim":"The discovery that TTLL5 (STAMP) associates with TIF2/SRC-1 and modulates glucocorticoid receptor-mediated gene induction and repression established a previously unknown transcriptional comodulator function for this protein, independent of its later-recognized enzymatic activity.","evidence":"Co-IP, ChIP on endogenous GR target promoters, siRNA knockdown with endogenous gene readouts, and reporter assays in mammalian cells","pmids":["17116691"],"confidence":"High","gaps":["Whether the transcriptional function depends on TTLL5 enzymatic (glutamylase) activity is unknown","The structural basis for TIF2–STAMP interaction is not resolved","Whether this comodulator role operates in vivo in relevant tissues has not been tested"]},{"year":2012,"claim":"Domain-dissection of the GR–TIF2–STAMP ternary complex revealed that distinct regions of each protein independently control different dose-response parameters (Amax, EC50, partial agonist activity), establishing that TTLL5 contributes to fine-tuning of transcriptional output rather than simple on/off regulation.","evidence":"Systematic transfection of 25 domain-fragment combinations with reporter and endogenous gene induction assays","pmids":["22342989"],"confidence":"Medium","gaps":["Mapping relies on overexpressed fragments without validation of endogenous domain requirements","Whether these parameters are modulated at endogenous loci genome-wide is untested"]},{"year":2013,"claim":"Generation of Ttll5-knockout mice demonstrated that TTLL5 is the principal α-tubulin polyglutamylase in sperm flagella, with its loss causing axonemal disassembly, immotile sperm, and male infertility — establishing the first in vivo enzymatic function of TTLL5.","evidence":"Targeted gene deletion in mice, electron microscopy of sperm axonemes, α-tubulin polyglutamylation assays, fertility tests","pmids":["23558686"],"confidence":"High","gaps":["Whether other TTLLs partially compensate in non-testicular tissues was not addressed","The mechanism by which polyglutamylation stabilizes axonemal doublets is not defined"]},{"year":2014,"claim":"Identification of biallelic TTLL5 mutations in patients with cone and macular dystrophies, combined with immunolocalization of TTLL5 to photoreceptor basal bodies, linked the enzyme's glutamylase activity to human retinal disease for the first time.","evidence":"Exome and Sanger sequencing of patient cohorts; immunolocalization in human and murine retinal sections","pmids":["24791901"],"confidence":"Medium","gaps":["No biochemical demonstration that the identified variants impair enzymatic activity was provided in this study","The relevant substrate in photoreceptors was not identified"]},{"year":2016,"claim":"Identification of RPGR(ORF15) as the critical TTLL5 substrate in photoreceptors — recruited via its C-terminal basic domain binding a TTLL5-specific cofactor interaction domain — unified the retinal and ciliary phenotypes by showing that TTLL5 loss abolishes RPGR glutamylation and phenocopies RPGR-null retinal degeneration, while human disease-causing TTLL5 mutations impair this modification.","evidence":"Co-IP in cells, Ttll5-mutant mouse with electrophysiology and opsin localization, mutagenesis of disease alleles with glutamylation assays","pmids":["27162334"],"confidence":"High","gaps":["How RPGR glutamylation mechanistically supports photoreceptor protein trafficking is not established","Whether additional non-tubulin substrates exist beyond RPGR(ORF15) is unknown"]},{"year":2016,"claim":"Clinical delineation of an allele-specific TTLL5 syndrome — truncating variants causing both retinopathy and male infertility while missense variants cause retinopathy alone — established genotype-phenotype correlations consistent with differential sensitivity of tubulin versus RPGR glutamylation to residual enzyme activity.","evidence":"NGS and autozygome screening in patient families; immunofluorescence on human sperm and rat retina; sperm motility assays","pmids":["28173158"],"confidence":"Medium","gaps":["The biochemical basis for why missense variants spare sperm function but not retinal function is not resolved","Cohort sizes remain small for definitive genotype-phenotype rules"]},{"year":null,"claim":"Key unresolved questions include the structural basis for TTLL5 substrate selectivity between tubulin and RPGR(ORF15), the relationship between its enzymatic and transcriptional comodulator activities, and whether additional non-tubulin substrates contribute to its ciliary or other functions.","evidence":"","pmids":[],"confidence":"Low","gaps":["No crystal or cryo-EM structure of TTLL5 is available","Whether the glutamylase catalytic activity is required for the GR comodulator function has never been tested","A comprehensive substrate profiling of TTLL5 in vivo has not been performed"]}],"mechanism_profile":{"molecular_activity":[{"term_id":"GO:0016874","term_label":"ligase activity","supporting_discovery_ids":[0,1]},{"term_id":"GO:0140110","term_label":"transcription regulator activity","supporting_discovery_ids":[4,5]}],"localization":[{"term_id":"GO:0005815","term_label":"microtubule organizing center","supporting_discovery_ids":[2,3]},{"term_id":"GO:0005929","term_label":"cilium","supporting_discovery_ids":[1,2,3]},{"term_id":"GO:0005634","term_label":"nucleus","supporting_discovery_ids":[4]}],"pathway":[{"term_id":"R-HSA-162582","term_label":"Signal Transduction","supporting_discovery_ids":[4,5]},{"term_id":"R-HSA-392499","term_label":"Metabolism of proteins","supporting_discovery_ids":[0,1]}],"complexes":["GR–TIF2–STAMP ternary complex"],"partners":["RPGR","TIF2","SRC1","NR3C1"],"other_free_text":[]},"mechanistic_narrative":"TTLL5 is a tubulin tyrosine ligase-like enzyme that catalyzes polyglutamylation of both α-tubulin and the photoreceptor-specific ciliary protein RPGR(ORF15), with critical roles in sperm axoneme integrity and photoreceptor maintenance. In the testis, TTLL5-mediated α-tubulin polyglutamylation is essential for axonemal doublet stability and progressive sperm motility, and its disruption causes male infertility [PMID:23558686]; in the retina, TTLL5 localizes to photoreceptor basal bodies and is the sole glutamylase that modifies RPGR(ORF15) via a unique cofactor interaction domain, with loss of this activity causing cone opsin mislocalization and photoreceptor degeneration [PMID:27162334]. Biallelic loss-of-function mutations in TTLL5 cause cone-rod and macular dystrophies in humans, with truncating alleles additionally impairing male fertility [PMID:24791901, PMID:28173158]. TTLL5 also functions as a transcriptional comodulator in glucocorticoid receptor signaling, forming a ternary complex with TIF2/SRC-1 coactivators to independently tune induction amplitude, EC50, and partial agonist activity of GR target genes [PMID:17116691, PMID:22342989]."},"prefetch_data":{"uniprot":{"accession":"Q6EMB2","full_name":"Tubulin polyglutamylase TTLL5","aliases":["SRC1 and TIF2-associated modulatory protein","STAMP protein","Tubulin--tyrosine ligase-like protein 5"],"length_aa":1281,"mass_kda":143.6,"function":"Polyglutamylase which modifies tubulin, generating polyglutamate side chains on the gamma-carboxyl group of specific glutamate residues within the C-terminal tail of tubulin. Preferentially mediates ATP-dependent initiation step of the polyglutamylation reaction over the elongation step. Preferentially modifies the alpha-tubulin tail over a beta-tail (By similarity). Required for CCSAP localization to both polyglutamylated spindle and cilia microtubules (PubMed:22493317). Increases the effects of transcriptional coactivator NCOA2/TIF2 in glucocorticoid receptor-mediated repression and induction and in androgen receptor-mediated induction (PubMed:17116691)","subcellular_location":"Cell projection, cilium; Cytoplasm, cytoskeleton, cilium basal body; Nucleus; Cytoplasm","url":"https://www.uniprot.org/uniprotkb/Q6EMB2/entry"},"depmap":{"release":"DepMap","has_data":true,"is_common_essential":false,"resolved_as":"","url":"https://depmap.org/portal/gene/TTLL5","classification":"Not Classified","n_dependent_lines":25,"n_total_lines":1208,"dependency_fraction":0.020695364238410598},"opencell":{"profiled":false,"resolved_as":"","ensg_id":"","cell_line_id":"","localizations":[],"interactors":[{"gene":"MVD","stoichiometry":0.2}],"url":"https://opencell.sf.czbiohub.org/search/TTLL5","total_profiled":1310},"omim":[{"mim_id":"620485","title":"TUBULIN TYROSINE LIGASE-LIKE 13; TTLL13","url":"https://www.omim.org/entry/620485"},{"mim_id":"618813","title":"TUBULIN TYROSINE LIGASE-LIKE 7; TTLL7","url":"https://www.omim.org/entry/618813"},{"mim_id":"617871","title":"RETINITIS PIGMENTOSA 81; RP81","url":"https://www.omim.org/entry/617871"},{"mim_id":"617649","title":"UBIQUITIN-CONJUGATING ENZYME E2 O; UBE2O","url":"https://www.omim.org/entry/617649"},{"mim_id":"617346","title":"ATP/GTP-BINDING PROTEIN-LIKE 3; AGBL3","url":"https://www.omim.org/entry/617346"}],"hpa":{"profiled":true,"resolved_as":"","reliability":"Approved","locations":[{"location":"Plasma membrane","reliability":"Approved"},{"location":"Cytosol","reliability":"Approved"}],"tissue_specificity":"Tissue enhanced","tissue_distribution":"Detected in all","driving_tissues":[{"tissue":"testis","ntpm":53.7}],"url":"https://www.proteinatlas.org/search/TTLL5"},"hgnc":{"alias_symbol":["STAMP"],"prev_symbol":["KIAA0998"]},"alphafold":{"accession":"Q6EMB2","domains":[{"cath_id":"-","chopping":"670-695_708-772_783-818","consensus_level":"high","plddt":81.9183,"start":670,"end":818}],"viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6EMB2","model_url":"https://alphafold.ebi.ac.uk/files/AF-Q6EMB2-F1-model_v6.cif","pae_url":"https://alphafold.ebi.ac.uk/files/AF-Q6EMB2-F1-predicted_aligned_error_v6.png","plddt_mean":61.41},"mouse_models":{"mgi_url":"https://www.informatics.jax.org/marker/summary?nomen=TTLL5","jax_strain_url":"https://www.jax.org/strain/search?query=TTLL5"},"sequence":{"accession":"Q6EMB2","fasta_url":"https://rest.uniprot.org/uniprotkb/Q6EMB2.fasta","uniprot_url":"https://www.uniprot.org/uniprotkb/Q6EMB2/entry","alphafold_viewer_url":"https://alphafold.ebi.ac.uk/entry/Q6EMB2"}},"corpus_meta":[{"pmid":"16061724","id":"PMC_16061724","title":"DC-STAMP is essential for cell-cell fusion in osteoclasts and foreign body giant cells.","date":"2005","source":"The Journal of experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/16061724","citation_count":719,"is_preprint":false},{"pmid":"17478497","id":"PMC_17478497","title":"STAMP: a web tool for exploring DNA-binding motif similarities.","date":"2007","source":"Nucleic acids research","url":"https://pubmed.ncbi.nlm.nih.gov/17478497","citation_count":371,"is_preprint":false},{"pmid":"17885208","id":"PMC_17885208","title":"NFATc1 induces osteoclast fusion via up-regulation of Atp6v0d2 and the dendritic cell-specific transmembrane protein (DC-STAMP).","date":"2007","source":"Molecular endocrinology (Baltimore, Md.)","url":"https://pubmed.ncbi.nlm.nih.gov/17885208","citation_count":366,"is_preprint":false},{"pmid":"15452179","id":"PMC_15452179","title":"RANKL-induced DC-STAMP is essential for osteoclastogenesis.","date":"2004","source":"The Journal of experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/15452179","citation_count":285,"is_preprint":false},{"pmid":"34407542","id":"PMC_34407542","title":"A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior TKIs.","date":"2021","source":"Blood","url":"https://pubmed.ncbi.nlm.nih.gov/34407542","citation_count":238,"is_preprint":false},{"pmid":"26592521","id":"PMC_26592521","title":"Aconine inhibits RANKL-induced osteoclast differentiation in RAW264.7 cells by suppressing NF-κB and NFATc1 activation and DC-STAMP expression.","date":"2015","source":"Acta pharmacologica Sinica","url":"https://pubmed.ncbi.nlm.nih.gov/26592521","citation_count":136,"is_preprint":false},{"pmid":"17402846","id":"PMC_17402846","title":"Induction of DC-STAMP by alternative activation and downstream signaling mechanisms.","date":"2007","source":"Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research","url":"https://pubmed.ncbi.nlm.nih.gov/17402846","citation_count":111,"is_preprint":false},{"pmid":"18064667","id":"PMC_18064667","title":"Osteoclast stimulatory transmembrane protein (OC-STAMP), a novel protein induced by RANKL that promotes osteoclast differentiation.","date":"2008","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/18064667","citation_count":109,"is_preprint":false},{"pmid":"16937266","id":"PMC_16937266","title":"Role of DC-STAMP in cellular fusion of osteoclasts and macrophage giant cells.","date":"2006","source":"Journal of bone and mineral metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/16937266","citation_count":97,"is_preprint":false},{"pmid":"27162334","id":"PMC_27162334","title":"Loss of RPGR glutamylation underlies the pathogenic mechanism of retinal dystrophy caused by TTLL5 mutations.","date":"2016","source":"Proceedings of the National Academy of Sciences of the United States of America","url":"https://pubmed.ncbi.nlm.nih.gov/27162334","citation_count":95,"is_preprint":false},{"pmid":"11169400","id":"PMC_11169400","title":"DC-STAMP, a novel multimembrane-spanning molecule preferentially expressed by dendritic cells.","date":"2000","source":"European journal of immunology","url":"https://pubmed.ncbi.nlm.nih.gov/11169400","citation_count":92,"is_preprint":false},{"pmid":"21987375","id":"PMC_21987375","title":"Regulation of human osteoclast development by dendritic cell-specific transmembrane protein (DC-STAMP).","date":"2012","source":"Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research","url":"https://pubmed.ncbi.nlm.nih.gov/21987375","citation_count":86,"is_preprint":false},{"pmid":"26439215","id":"PMC_26439215","title":"The S-stamp in Descemet Membrane Endothelial Keratoplasty Safely Eliminates Upside-down Graft Implantation.","date":"2015","source":"Ophthalmology","url":"https://pubmed.ncbi.nlm.nih.gov/26439215","citation_count":84,"is_preprint":false},{"pmid":"27018136","id":"PMC_27018136","title":"DC-STAMP: A Key Regulator in Osteoclast Differentiation.","date":"2016","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/27018136","citation_count":83,"is_preprint":false},{"pmid":"20039274","id":"PMC_20039274","title":"RANKL induces heterogeneous DC-STAMP(lo) and DC-STAMP(hi) osteoclast precursors of which the DC-STAMP(lo) precursors are the master fusogens.","date":"2010","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/20039274","citation_count":83,"is_preprint":false},{"pmid":"25123438","id":"PMC_25123438","title":"MiR-7b directly targets DC-STAMP causing suppression of NFATc1 and c-Fos signaling during osteoclast fusion and differentiation.","date":"2014","source":"Biochimica et biophysica acta","url":"https://pubmed.ncbi.nlm.nih.gov/25123438","citation_count":77,"is_preprint":false},{"pmid":"24791901","id":"PMC_24791901","title":"Biallelic variants in TTLL5, encoding a tubulin glutamylase, cause retinal dystrophy.","date":"2014","source":"American journal of human genetics","url":"https://pubmed.ncbi.nlm.nih.gov/24791901","citation_count":74,"is_preprint":false},{"pmid":"24420845","id":"PMC_24420845","title":"DC-STAMP, the key fusion-mediating molecule in osteoclastogenesis.","date":"2014","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/24420845","citation_count":64,"is_preprint":false},{"pmid":"26042409","id":"PMC_26042409","title":"Studies of OC-STAMP in Osteoclast Fusion: A New Knockout Mouse Model, Rescue of Cell Fusion, and Transmembrane Topology.","date":"2015","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/26042409","citation_count":60,"is_preprint":false},{"pmid":"20721934","id":"PMC_20721934","title":"CCN family 2/connective tissue growth factor (CCN2/CTGF) promotes osteoclastogenesis via induction of and interaction with dendritic cell-specific transmembrane protein (DC-STAMP).","date":"2011","source":"Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research","url":"https://pubmed.ncbi.nlm.nih.gov/20721934","citation_count":59,"is_preprint":false},{"pmid":"34560015","id":"PMC_34560015","title":"Efficacy and safety of PXL770, a direct AMP kinase activator, for the treatment of non-alcoholic fatty liver disease (STAMP-NAFLD): a randomised, double-blind, placebo-controlled, phase 2a study.","date":"2021","source":"The lancet. Gastroenterology & hepatology","url":"https://pubmed.ncbi.nlm.nih.gov/34560015","citation_count":58,"is_preprint":false},{"pmid":"23444125","id":"PMC_23444125","title":"Foreign body giant cells and osteoclasts are TRAP positive, have podosome-belts and both require OC-STAMP for cell fusion.","date":"2013","source":"Journal of cellular biochemistry","url":"https://pubmed.ncbi.nlm.nih.gov/23444125","citation_count":52,"is_preprint":false},{"pmid":"21044666","id":"PMC_21044666","title":"The stolbur phytoplasma antigenic membrane protein gene stamp is submitted to diversifying positive selection.","date":"2010","source":"Gene","url":"https://pubmed.ncbi.nlm.nih.gov/21044666","citation_count":50,"is_preprint":false},{"pmid":"23558686","id":"PMC_23558686","title":"Disruption of Ttll5/stamp gene (tubulin tyrosine ligase-like protein 5/SRC-1 and TIF2-associated modulatory protein gene) in male mice causes sperm malformation and infertility.","date":"2013","source":"The Journal of biological chemistry","url":"https://pubmed.ncbi.nlm.nih.gov/23558686","citation_count":49,"is_preprint":false},{"pmid":"23629863","id":"PMC_23629863","title":"Resolvin E1 regulates osteoclast fusion via DC-STAMP and NFATc1.","date":"2013","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/23629863","citation_count":49,"is_preprint":false},{"pmid":"10816028","id":"PMC_10816028","title":"Cardiac toxicity following high-dose cyclophosphamide, cisplatin, and BCNU (STAMP-I) for breast cancer.","date":"2000","source":"Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation","url":"https://pubmed.ncbi.nlm.nih.gov/10816028","citation_count":49,"is_preprint":false},{"pmid":"23434822","id":"PMC_23434822","title":"Caffeine enhances osteoclast differentiation and maturation through p38 MAP kinase/Mitf and DC-STAMP/CtsK and TRAP pathway.","date":"2013","source":"Cellular signalling","url":"https://pubmed.ncbi.nlm.nih.gov/23434822","citation_count":48,"is_preprint":false},{"pmid":"23980096","id":"PMC_23980096","title":"Strawberry notch homologue 2 regulates osteoclast fusion by enhancing the expression of DC-STAMP.","date":"2013","source":"The Journal of experimental medicine","url":"https://pubmed.ncbi.nlm.nih.gov/23980096","citation_count":43,"is_preprint":false},{"pmid":"17164993","id":"PMC_17164993","title":"The dendritic cell-specific transmembrane protein DC-STAMP is essential for osteoclast fusion and osteoclast bone-resorbing activity.","date":"2006","source":"Modern rheumatology","url":"https://pubmed.ncbi.nlm.nih.gov/17164993","citation_count":41,"is_preprint":false},{"pmid":"20546900","id":"PMC_20546900","title":"DC-STAMP interacts with ER-resident transcription factor LUMAN which becomes activated during DC maturation.","date":"2010","source":"Molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/20546900","citation_count":40,"is_preprint":false},{"pmid":"31827757","id":"PMC_31827757","title":"High-throughput three-dimensional spheroid tumor model using a novel stamp-like tool.","date":"2019","source":"Journal of tissue engineering","url":"https://pubmed.ncbi.nlm.nih.gov/31827757","citation_count":39,"is_preprint":false},{"pmid":"31985196","id":"PMC_31985196","title":"Self-Healable Hydrogel-Liquid Metal Composite Platform Enabled by a 3D Printed Stamp for a Multimodular Sensor System.","date":"2020","source":"ACS applied materials & interfaces","url":"https://pubmed.ncbi.nlm.nih.gov/31985196","citation_count":38,"is_preprint":false},{"pmid":"9357321","id":"PMC_9357321","title":"Identifying neuronal non-L Ca2+ channels--more than stamp collecting?","date":"1997","source":"Trends in pharmacological sciences","url":"https://pubmed.ncbi.nlm.nih.gov/9357321","citation_count":37,"is_preprint":false},{"pmid":"28173158","id":"PMC_28173158","title":"Mutations in the polyglutamylase gene TTLL5, expressed in photoreceptor cells and spermatozoa, are associated with cone-rod degeneration and reduced male fertility.","date":"2016","source":"Human molecular genetics","url":"https://pubmed.ncbi.nlm.nih.gov/28173158","citation_count":36,"is_preprint":false},{"pmid":"19183437","id":"PMC_19183437","title":"STAMP: Extensions to the STADEN sequence analysis package for high throughput interactive microsatellite marker design.","date":"2009","source":"BMC bioinformatics","url":"https://pubmed.ncbi.nlm.nih.gov/19183437","citation_count":35,"is_preprint":false},{"pmid":"32887359","id":"PMC_32887359","title":"Fusion Potential of Human Osteoclasts In Vitro Reflects Age, Menopause, and In Vivo Bone Resorption Levels of Their Donors-A Possible Involvement of DC-STAMP.","date":"2020","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/32887359","citation_count":35,"is_preprint":false},{"pmid":"17116691","id":"PMC_17116691","title":"STAMP, a novel predicted factor assisting TIF2 actions in glucocorticoid receptor-mediated induction and repression.","date":"2006","source":"Molecular and cellular biology","url":"https://pubmed.ncbi.nlm.nih.gov/17116691","citation_count":34,"is_preprint":false},{"pmid":"27723141","id":"PMC_27723141","title":"Dendritic Cell-Specific Transmembrane Protein (DC-STAMP) Regulates Osteoclast Differentiation via the Ca2+ /NFATc1 Axis.","date":"2017","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/27723141","citation_count":33,"is_preprint":false},{"pmid":"24891219","id":"PMC_24891219","title":"Pin1 regulates osteoclast fusion through suppression of the master regulator of cell fusion DC-STAMP.","date":"2014","source":"Journal of cellular physiology","url":"https://pubmed.ncbi.nlm.nih.gov/24891219","citation_count":33,"is_preprint":false},{"pmid":"21990371","id":"PMC_21990371","title":"Tal1 regulates osteoclast differentiation through suppression of the master regulator of cell fusion DC-STAMP.","date":"2011","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/21990371","citation_count":33,"is_preprint":false},{"pmid":"18653699","id":"PMC_18653699","title":"The role of DC-STAMP in maintenance of immune tolerance through regulation of dendritic cell function.","date":"2008","source":"International immunology","url":"https://pubmed.ncbi.nlm.nih.gov/18653699","citation_count":33,"is_preprint":false},{"pmid":"29533736","id":"PMC_29533736","title":"OC-STAMP promotes osteoclast fusion for pathogenic bone resorption in periodontitis via up-regulation of permissive fusogen CD9.","date":"2018","source":"FASEB journal : official publication of the Federation of American Societies for Experimental Biology","url":"https://pubmed.ncbi.nlm.nih.gov/29533736","citation_count":33,"is_preprint":false},{"pmid":"30909479","id":"PMC_30909479","title":"Safety and Usefulness of Cryobiopsy and Stamp Cytology for the Diagnosis of Peripheral Pulmonary Lesions.","date":"2019","source":"Cancers","url":"https://pubmed.ncbi.nlm.nih.gov/30909479","citation_count":32,"is_preprint":false},{"pmid":"15601667","id":"PMC_15601667","title":"The dendritic cell-derived protein DC-STAMP is highly conserved and localizes to the endoplasmic reticulum.","date":"2004","source":"Journal of leukocyte biology","url":"https://pubmed.ncbi.nlm.nih.gov/15601667","citation_count":32,"is_preprint":false},{"pmid":"20949218","id":"PMC_20949218","title":"Millimeter-scale contact printing of aqueous solutions using a stamp made out of paper and tape.","date":"2010","source":"Lab on a chip","url":"https://pubmed.ncbi.nlm.nih.gov/20949218","citation_count":32,"is_preprint":false},{"pmid":"37252938","id":"PMC_37252938","title":"STAMP-Based Digital CRISPR-Cas13a for Amplification-Free Quantification of HIV-1 Plasma Viral Loads.","date":"2023","source":"ACS nano","url":"https://pubmed.ncbi.nlm.nih.gov/37252938","citation_count":30,"is_preprint":false},{"pmid":"28199142","id":"PMC_28199142","title":"DC-STAMP Is an Osteoclast Fusogen Engaged in Periodontal Bone Resorption.","date":"2017","source":"Journal of dental research","url":"https://pubmed.ncbi.nlm.nih.gov/28199142","citation_count":30,"is_preprint":false},{"pmid":"26003218","id":"PMC_26003218","title":"It's more than stamp collecting: how genome sequencing can unify biological research.","date":"2015","source":"Trends in genetics : TIG","url":"https://pubmed.ncbi.nlm.nih.gov/26003218","citation_count":29,"is_preprint":false},{"pmid":"23994170","id":"PMC_23994170","title":"Mechanical vibration inhibits osteoclast formation by reducing DC-STAMP receptor expression in osteoclast precursor cells.","date":"2013","source":"Bone","url":"https://pubmed.ncbi.nlm.nih.gov/23994170","citation_count":29,"is_preprint":false},{"pmid":"29312525","id":"PMC_29312525","title":"MiR-30a attenuates osteoclastogenesis via targeting DC-STAMP-c-Fos-NFATc1 signaling.","date":"2017","source":"American journal of translational research","url":"https://pubmed.ncbi.nlm.nih.gov/29312525","citation_count":28,"is_preprint":false},{"pmid":"15469654","id":"PMC_15469654","title":"Socio-economic and behavioural factors are predictors of food use in the National Food Stamp Program Survey.","date":"2004","source":"The British journal of nutrition","url":"https://pubmed.ncbi.nlm.nih.gov/15469654","citation_count":28,"is_preprint":false},{"pmid":"39407016","id":"PMC_39407016","title":"Interpretable spatially aware dimension reduction of spatial transcriptomics with STAMP.","date":"2024","source":"Nature methods","url":"https://pubmed.ncbi.nlm.nih.gov/39407016","citation_count":27,"is_preprint":false},{"pmid":"25296251","id":"PMC_25296251","title":"HIV: A stamp on the envelope.","date":"2014","source":"Nature","url":"https://pubmed.ncbi.nlm.nih.gov/25296251","citation_count":26,"is_preprint":false},{"pmid":"22262219","id":"PMC_22262219","title":"The endothelial safety of using a gentian violet dry-ink \"S\" stamp for precut corneal tissue.","date":"2012","source":"Cornea","url":"https://pubmed.ncbi.nlm.nih.gov/22262219","citation_count":26,"is_preprint":false},{"pmid":"26503158","id":"PMC_26503158","title":"Luman is involved in osteoclastogenesis through the regulation of DC-STAMP expression, stability and localization.","date":"2015","source":"Journal of cell science","url":"https://pubmed.ncbi.nlm.nih.gov/26503158","citation_count":24,"is_preprint":false},{"pmid":"17905603","id":"PMC_17905603","title":"Time stamp in conditioned place avoidance can be set to different circadian phases.","date":"2007","source":"Neurobiology of learning and memory","url":"https://pubmed.ncbi.nlm.nih.gov/17905603","citation_count":24,"is_preprint":false},{"pmid":"20961056","id":"PMC_20961056","title":"Stamp wound assay for studying coupled cell migration and cell debris clearance.","date":"2010","source":"Langmuir : the ACS journal of surfaces and colloids","url":"https://pubmed.ncbi.nlm.nih.gov/20961056","citation_count":23,"is_preprint":false},{"pmid":"8195763","id":"PMC_8195763","title":"The use of minisatellite variant repeat-polymerase chain reaction (MVR-PCR) to determine the source of saliva on a used postage stamp.","date":"1994","source":"Journal of forensic sciences","url":"https://pubmed.ncbi.nlm.nih.gov/8195763","citation_count":23,"is_preprint":false},{"pmid":"18952287","id":"PMC_18952287","title":"OS9 interacts with DC-STAMP and modulates its intracellular localization in response to TLR ligation.","date":"2008","source":"Molecular immunology","url":"https://pubmed.ncbi.nlm.nih.gov/18952287","citation_count":22,"is_preprint":false},{"pmid":"25151085","id":"PMC_25151085","title":"Comparison of periprosthetic tissues in knee and hip joints: differential expression of CCL3 and DC-STAMP in total knee and hip arthroplasty and similar cytokine profiles in primary knee and hip osteoarthritis.","date":"2014","source":"Osteoarthritis and cartilage","url":"https://pubmed.ncbi.nlm.nih.gov/25151085","citation_count":22,"is_preprint":false},{"pmid":"32753731","id":"PMC_32753731","title":"Oridonin ameliorates inflammation-induced bone loss in mice via suppressing DC-STAMP expression.","date":"2020","source":"Acta pharmacologica Sinica","url":"https://pubmed.ncbi.nlm.nih.gov/32753731","citation_count":20,"is_preprint":false},{"pmid":"32707439","id":"PMC_32707439","title":"Comparison of mitochondrial transplantation by using a stamp-type multineedle injector and platelet-rich plasma therapy for hair aging in naturally aging mice.","date":"2020","source":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","url":"https://pubmed.ncbi.nlm.nih.gov/32707439","citation_count":20,"is_preprint":false},{"pmid":"35056817","id":"PMC_35056817","title":"Melatonin Attenuates RANKL-Induced Osteoclastogenesis via Inhibition of Atp6v0d2 and DC-STAMP through MAPK and NFATc1 Signaling Pathways.","date":"2022","source":"Molecules (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/35056817","citation_count":19,"is_preprint":false},{"pmid":"23292096","id":"PMC_23292096","title":"Short-term mechanical stress inhibits osteoclastogenesis via suppression of DC-STAMP in RAW264.7 cells.","date":"2012","source":"International journal of molecular medicine","url":"https://pubmed.ncbi.nlm.nih.gov/23292096","citation_count":18,"is_preprint":false},{"pmid":"29514329","id":"PMC_29514329","title":"Validation of the Subjective Global Nutrition Assessment (SGNA) and Screening Tool for the Assessment of Malnutrition in Paediatrics (STAMP) to Identify Malnutrition in Hospitalized Malaysian Children.","date":"2019","source":"Journal of tropical pediatrics","url":"https://pubmed.ncbi.nlm.nih.gov/29514329","citation_count":18,"is_preprint":false},{"pmid":"27979663","id":"PMC_27979663","title":"Sulforaphane inhibits osteoclast differentiation by suppressing the cell-cell fusion molecules DC-STAMP and OC-STAMP.","date":"2016","source":"Biochemical and biophysical research communications","url":"https://pubmed.ncbi.nlm.nih.gov/27979663","citation_count":18,"is_preprint":false},{"pmid":"20882308","id":"PMC_20882308","title":"Molecules and signaling pathways involved in the expression of OC-STAMP during osteoclastogenesis.","date":"2010","source":"Amino acids","url":"https://pubmed.ncbi.nlm.nih.gov/20882308","citation_count":17,"is_preprint":false},{"pmid":"21677946","id":"PMC_21677946","title":"DNA manipulation with elastomeric nanostructures fabricated by soft-moulding of a FIB-patterned stamp.","date":"2011","source":"Lab on a chip","url":"https://pubmed.ncbi.nlm.nih.gov/21677946","citation_count":17,"is_preprint":false},{"pmid":"37275638","id":"PMC_37275638","title":"Deciphering the mechanism of jujube vinegar on hyperlipoidemia through gut microbiome based on 16S rRNA, BugBase analysis, and the stamp analysis of KEEG.","date":"2023","source":"Frontiers in nutrition","url":"https://pubmed.ncbi.nlm.nih.gov/37275638","citation_count":17,"is_preprint":false},{"pmid":"23467706","id":"PMC_23467706","title":"Safety evaluation of stamp type digital microneedle devices in hairless mice.","date":"2013","source":"Annals of dermatology","url":"https://pubmed.ncbi.nlm.nih.gov/23467706","citation_count":17,"is_preprint":false},{"pmid":"23525827","id":"PMC_23525827","title":"Lentivirus-mediated RNA interference of DC-STAMP expression inhibits the fusion and resorptive activity of human osteoclasts.","date":"2013","source":"Journal of bone and mineral metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/23525827","citation_count":16,"is_preprint":false},{"pmid":"21538866","id":"PMC_21538866","title":"Tuning stamp surface energy for soft lithography of polar molecules to fabricate bioactive small-molecule microarrays.","date":"2011","source":"Small (Weinheim an der Bergstrasse, Germany)","url":"https://pubmed.ncbi.nlm.nih.gov/21538866","citation_count":16,"is_preprint":false},{"pmid":"34203883","id":"PMC_34203883","title":"Novel TTLL5 Variants Associated with Cone-Rod Dystrophy and Early-Onset Severe Retinal Dystrophy.","date":"2021","source":"International journal of molecular sciences","url":"https://pubmed.ncbi.nlm.nih.gov/34203883","citation_count":15,"is_preprint":false},{"pmid":"23874564","id":"PMC_23874564","title":"Differential expression and function of stamp family proteins in adipocyte differentiation.","date":"2013","source":"PloS one","url":"https://pubmed.ncbi.nlm.nih.gov/23874564","citation_count":15,"is_preprint":false},{"pmid":"21978263","id":"PMC_21978263","title":"DC-STAMP knock-down deregulates cytokine production and T-cell stimulatory capacity of LPS-matured dendritic cells.","date":"2011","source":"BMC immunology","url":"https://pubmed.ncbi.nlm.nih.gov/21978263","citation_count":15,"is_preprint":false},{"pmid":"38535538","id":"PMC_38535538","title":"Oral Microbiome Stamp in Alzheimer's Disease.","date":"2024","source":"Pathogens (Basel, Switzerland)","url":"https://pubmed.ncbi.nlm.nih.gov/38535538","citation_count":14,"is_preprint":false},{"pmid":"23624721","id":"PMC_23624721","title":"Lysophosphatidic acid stimulates osteoclast fusion through OC-STAMP and P2X7 receptor signaling.","date":"2013","source":"Journal of bone and mineral metabolism","url":"https://pubmed.ncbi.nlm.nih.gov/23624721","citation_count":14,"is_preprint":false},{"pmid":"24439276","id":"PMC_24439276","title":"\"Stamp-off\" to micropattern sparse, multicomponent features.","date":"2014","source":"Methods in cell biology","url":"https://pubmed.ncbi.nlm.nih.gov/24439276","citation_count":14,"is_preprint":false},{"pmid":"37058234","id":"PMC_37058234","title":"Combination Treatment with Sipuleucel-T and Abiraterone Acetate or Enzalutamide for Metastatic Castration-Resistant Prostate Cancer: STAMP and STRIDE Trials.","date":"2023","source":"Clinical cancer research : an official journal of the American Association for Cancer Research","url":"https://pubmed.ncbi.nlm.nih.gov/37058234","citation_count":14,"is_preprint":false},{"pmid":"34426759","id":"PMC_34426759","title":"OC-STAMP Overexpression Drives Lung Alveolar Epithelial Cell Type II Senescence in Silicosis.","date":"2021","source":"Oxidative medicine and cellular longevity","url":"https://pubmed.ncbi.nlm.nih.gov/34426759","citation_count":13,"is_preprint":false},{"pmid":"12017145","id":"PMC_12017145","title":"The impact of induction duration and the number of high-dose cycles on the long-term survival of women with metastatic breast cancer treated with high-dose chemotherapy with stem cell rescue: an analysis of sequential phase I/II trials from the Dana-Farber/Beth Israel STAMP program.","date":"2002","source":"Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation","url":"https://pubmed.ncbi.nlm.nih.gov/12017145","citation_count":12,"is_preprint":false},{"pmid":"28410359","id":"PMC_28410359","title":"Intraoperative S-Stamp Enabled Rescue of 3 Inverted Descemet Membrane Endothelial Keratoplasty Grafts.","date":"2017","source":"Cornea","url":"https://pubmed.ncbi.nlm.nih.gov/28410359","citation_count":12,"is_preprint":false},{"pmid":"37169395","id":"PMC_37169395","title":"Comparison of TRIBE and STAMP for identifying targets of RNA binding proteins in human and Drosophila cells.","date":"2023","source":"RNA (New York, N.Y.)","url":"https://pubmed.ncbi.nlm.nih.gov/37169395","citation_count":12,"is_preprint":false},{"pmid":"40532697","id":"PMC_40532697","title":"STAMP: Single-cell transcriptomics analysis and multimodal profiling through imaging.","date":"2025","source":"Cell","url":"https://pubmed.ncbi.nlm.nih.gov/40532697","citation_count":11,"is_preprint":false},{"pmid":"33134911","id":"PMC_33134911","title":"STAMP: a multiplex sequencing method for simultaneous evaluation of mitochondrial DNA heteroplasmies and content.","date":"2020","source":"NAR genomics and bioinformatics","url":"https://pubmed.ncbi.nlm.nih.gov/33134911","citation_count":11,"is_preprint":false},{"pmid":"17237326","id":"PMC_17237326","title":"Added sugars displaced the use of vital nutrients in the National Food Stamp Program Survey.","date":"2007","source":"The Journal of nutrition","url":"https://pubmed.ncbi.nlm.nih.gov/17237326","citation_count":11,"is_preprint":false},{"pmid":"22342989","id":"PMC_22342989","title":"Separate regions of glucocorticoid receptor, coactivator TIF2, and comodulator STAMP modify different parameters of glucocorticoid-mediated gene induction.","date":"2012","source":"Molecular and cellular endocrinology","url":"https://pubmed.ncbi.nlm.nih.gov/22342989","citation_count":11,"is_preprint":false},{"pmid":"28356705","id":"PMC_28356705","title":"Novel splice-site mutation in TTLL5 causes cone dystrophy in a consanguineous family.","date":"2017","source":"Molecular vision","url":"https://pubmed.ncbi.nlm.nih.gov/28356705","citation_count":10,"is_preprint":false},{"pmid":"30404347","id":"PMC_30404347","title":"A Simple Method for Fabrication of Microstructures Using a PDMS Stamp.","date":"2016","source":"Micromachines","url":"https://pubmed.ncbi.nlm.nih.gov/30404347","citation_count":10,"is_preprint":false},{"pmid":"12357676","id":"PMC_12357676","title":"[Definitive ability of Stamp-staining, antigen-ELISA, PCR and cell culture for the detection of Coxiella burnetii].","date":"2002","source":"Berliner und Munchener tierarztliche Wochenschrift","url":"https://pubmed.ncbi.nlm.nih.gov/12357676","citation_count":10,"is_preprint":false},{"pmid":"22081085","id":"PMC_22081085","title":"All-silica nanofluidic devices for DNA-analysis fabricated by imprint of sol-gel silica with silicon stamp.","date":"2011","source":"Lab on a chip","url":"https://pubmed.ncbi.nlm.nih.gov/22081085","citation_count":10,"is_preprint":false},{"pmid":"37580661","id":"PMC_37580661","title":"Efficacy and safety of fluzoparib combined with anlotinib in extensive stage small cell lung cancer after first-line platinum-based chemotherapy: a multi-center, single-arm prospective phase II clinical study (STAMP study).","date":"2023","source":"BMC cancer","url":"https://pubmed.ncbi.nlm.nih.gov/37580661","citation_count":9,"is_preprint":false},{"pmid":"37102603","id":"PMC_37102603","title":"Asciminib in chronic myeloid leukemia: a STAMP for expedited delivery?","date":"2023","source":"Haematologica","url":"https://pubmed.ncbi.nlm.nih.gov/37102603","citation_count":8,"is_preprint":false},{"pmid":"27387591","id":"PMC_27387591","title":"Serial multiple crossed immunoelectrophoresis at a microscale: A stamp-sized 2D immunoanalysis of protein C3 activation caused by nanoparticles.","date":"2016","source":"Electrophoresis","url":"https://pubmed.ncbi.nlm.nih.gov/27387591","citation_count":8,"is_preprint":false},{"pmid":"38906680","id":"PMC_38906680","title":"Long-read Ribo-STAMP simultaneously measures transcription and translation with isoform resolution.","date":"2024","source":"Genome research","url":"https://pubmed.ncbi.nlm.nih.gov/38906680","citation_count":7,"is_preprint":false},{"pmid":"20374646","id":"PMC_20374646","title":"STAMP alters the growth of transformed and ovarian cancer cells.","date":"2010","source":"BMC cancer","url":"https://pubmed.ncbi.nlm.nih.gov/20374646","citation_count":7,"is_preprint":false},{"pmid":"20831919","id":"PMC_20831919","title":"Gymnasterkoreayne F inhibits osteoclast formation by suppressing NFATc1 and DC-STAMP expression.","date":"2010","source":"International immunopharmacology","url":"https://pubmed.ncbi.nlm.nih.gov/20831919","citation_count":7,"is_preprint":false},{"pmid":"12629998","id":"PMC_12629998","title":"Utility of serosal stamp cytology as an indicator for high-risk peritoneal metastasis in colorectal cancer surgery.","date":"2003","source":"Hepato-gastroenterology","url":"https://pubmed.ncbi.nlm.nih.gov/12629998","citation_count":7,"is_preprint":false},{"pmid":"36347558","id":"PMC_36347558","title":"TRIBE-STAMP reveals new insights into the functions of RNA binding proteins.","date":"2022","source":"Genes & development","url":"https://pubmed.ncbi.nlm.nih.gov/36347558","citation_count":6,"is_preprint":false},{"pmid":"35365235","id":"PMC_35365235","title":"Expanding the phenotype of TTLL5-associated retinal dystrophy: a case series.","date":"2022","source":"Orphanet journal of rare diseases","url":"https://pubmed.ncbi.nlm.nih.gov/35365235","citation_count":6,"is_preprint":false}],"cost":{"stage1":{"model":"claude-sonnet-4-6","input_tokens":48666,"output_tokens":2263,"usd":0.089971},"stage2":{"model":"claude-opus-4-6","input_tokens":5552,"output_tokens":2155,"usd":0.122453},"total_usd":0.212424,"stage1_batch_id":"msgbatch_01RPbVc9PDH9zQmYK5Hs6srm","stage2_batch_id":"msgbatch_01JVbVLzeKN2yVrsGp3zC8aM","note":"batch pricing = 50% of standard"},"stage1_raw":"```json\n{\n  \"discoveries\": [\n    {\n      \"year\": 2016,\n      \"finding\": \"TTLL5 glutamylates RPGR(ORF15) in its Glu-Gly-rich repetitive region; the RPGR(ORF15) C-terminal basic domain binds the noncatalytic cofactor interaction domain unique to TTLL5 and targets TTLL5 to glutamylate RPGR. Only TTLL5 (not other TTLL family glutamylases) interacts with RPGR(ORF15) in cells. A Ttll5 mutant mouse shows complete loss of RPGR glutamylation without marked changes in tubulin glutamylation, and develops photoreceptor degeneration with mislocalization of cone opsins similar to Rpgr-null mice. TTLL5 disease mutants causing human retinal dystrophy show impaired glutamylation of RPGR(ORF15).\",\n      \"method\": \"Co-IP, in vivo mutagenesis, Ttll5 mutant mouse model, immunofluorescence, electroretinography\",\n      \"journal\": \"Proceedings of the National Academy of Sciences of the United States of America\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 1-2 — multiple orthogonal methods (Co-IP, reconstitution in cells, in vivo KO mouse, mutagenesis of disease alleles) in a single rigorous study\",\n      \"pmids\": [\"27162334\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2013,\n      \"finding\": \"Disruption of the Ttll5/Stamp gene in male mice causes defective α-tubulin polyglutamylation specifically in sperm tails, leading to abnormal axonemal structures with loss of tubulin doublets, reduced progressive sperm motility, and male infertility. The phenotype is tissue-selective (testes express STAMP mRNA 20-fold higher than any other organ) and unrelated to other Ttll genes or 24 genes previously linked to sperm function.\",\n      \"method\": \"Targeted gene deletion mouse model, electron microscopy of sperm axonemes, α-tubulin polyglutamylation assay, fertility assays, qRT-PCR\",\n      \"journal\": \"The Journal of biological chemistry\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — clean KO mouse with defined cellular and biochemical phenotype, multiple orthogonal methods\",\n      \"pmids\": [\"23558686\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2014,\n      \"finding\": \"Biallelic loss-of-function variants in TTLL5, which encodes a tubulin glutamylase, cause cone, cone-rod, and macular dystrophies in humans. In human and murine retinae, TTLL5 localizes to the centrioles at the base of the connecting cilium of photoreceptors, and TTLL5 has been reported to be essential for correct sperm flagella function and to play a role in polyglutamylation of primary cilia in vitro.\",\n      \"method\": \"Exome sequencing, Sanger sequencing, immunolocalization in retinal sections\",\n      \"journal\": \"American journal of human genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — human genetics plus direct immunolocalization; mechanistic link to glutamylation inferred from prior literature cited in paper\",\n      \"pmids\": [\"24791901\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2016,\n      \"finding\": \"Mutations in TTLL5 delineate an allele-specific syndrome affecting both vision and reproduction: truncating variants cause cone-dominated retinopathy and substantially reduced sperm motility/infertility in male patients, whereas missense variants cause retinopathy without infertility. TTLL5 antibodies stain the basal body of photoreceptor cells in rat retina and the centrosome of the spermatozoon flagellum in humans, indicating a shared polyglutamylase mechanism in these two cell types.\",\n      \"method\": \"Next-generation sequencing, autozygome screening, immunofluorescence on human/rat tissues, sperm motility assays\",\n      \"journal\": \"Human molecular genetics\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2-3 — human genetics with direct immunolocalization in two species; functional consequence of truncating vs. missense alleles established\",\n      \"pmids\": [\"28173158\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2006,\n      \"finding\": \"STAMP (TTLL5) was identified as a novel 1,277-amino-acid endogenous protein that associates with coactivators TIF2 and SRC-1 and is selective for a subset of steroid/nuclear receptors including glucocorticoid receptor (GR). Transfected STAMP increases the effects of TIF2 in GR-mediated gene repression and induction; siRNA knockdown of endogenous STAMP reduces both induction and repression of endogenous GR target genes. Endogenous STAMP colocalizes with GR in intact cells and is recruited to promoters of GR-induced and GR-repressed genes.\",\n      \"method\": \"Co-IP, siRNA knockdown of endogenous gene, ChIP on endogenous promoters, co-localization by immunofluorescence, reporter gene assays\",\n      \"journal\": \"Molecular and cellular biology\",\n      \"confidence\": \"High\",\n      \"confidence_rationale\": \"Tier 2 — multiple orthogonal methods (Co-IP, ChIP, siRNA with endogenous gene readouts, co-localization) in a single study\",\n      \"pmids\": [\"17116691\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2012,\n      \"finding\": \"Separate regions of TTLL5/STAMP, coactivator TIF2, and glucocorticoid receptor (GR) independently modify different parameters of GR-mediated gene induction (Amax, EC50, partial agonist activity), demonstrating that these three parameters can be independently regulated by different protein domains within a ternary GR–TIF2–STAMP complex.\",\n      \"method\": \"Transfection of 25 fragment combinations, reporter gene assays for Amax/EC50/PAA, endogenous gene induction assays\",\n      \"journal\": \"Molecular and cellular endocrinology\",\n      \"confidence\": \"Medium\",\n      \"confidence_rationale\": \"Tier 2 — systematic domain-dissection with multiple functional readouts in a single study\",\n      \"pmids\": [\"22342989\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2010,\n      \"finding\": \"TTLL5/STAMP overexpression reduces proliferation of HEK293 cells in a steroid-independent manner; siRNA-mediated knockdown of STAMP mRNA alters proliferation of ovarian cancer cell lines in a cell-line-specific fashion, indicating a physiological role for STAMP in regulating cell growth rates independently of steroid hormones.\",\n      \"method\": \"Stable STAMP overexpression in HEK293 cells, siRNA knockdown, proliferation assays across multiple cancer cell lines\",\n      \"journal\": \"BMC cancer\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3 — single lab, single functional readout (proliferation), no defined molecular pathway for the growth effect\",\n      \"pmids\": [\"20374646\"],\n      \"is_preprint\": false\n    },\n    {\n      \"year\": 2021,\n      \"finding\": \"Novel biallelic variants in TTLL5 cause cone-rod dystrophy and early-onset severe retinal dystrophy; protein modeling of identified variants suggests different effects on protein function, providing a potential basis for genotype-phenotype correlation.\",\n      \"method\": \"Targeted NGS gene panels, CNV analysis, protein structural modeling, ERG, OCT, autofluorescence imaging\",\n      \"journal\": \"International journal of molecular sciences\",\n      \"confidence\": \"Low\",\n      \"confidence_rationale\": \"Tier 3-4 — mechanistic inference from structural modeling only; clinical genetics study without direct biochemical validation\",\n      \"pmids\": [\"34203883\"],\n      \"is_preprint\": false\n    }\n  ],\n  \"current_model\": \"TTLL5 is a tubulin tyrosine ligase-like polyglutamylase that catalyzes polyglutamylation of both α-tubulin (required for sperm axoneme integrity and male fertility) and the photoreceptor-specific protein RPGR(ORF15) (required for photoreceptor function); RPGR(ORF15) is recruited as a substrate via its C-terminal basic domain binding to a noncatalytic cofactor interaction domain unique to TTLL5, and TTLL5 additionally functions as a transcriptional comodulator in glucocorticoid receptor signaling by forming a ternary complex with TIF2/SRC-1 coactivators to tune gene induction and repression parameters.\"\n}\n```","stage2_raw":"```json\n{\n  \"mechanistic_narrative\": \"TTLL5 is a tubulin tyrosine ligase-like enzyme that catalyzes polyglutamylation of both α-tubulin and the photoreceptor-specific ciliary protein RPGR(ORF15), with critical roles in sperm axoneme integrity and photoreceptor maintenance. In the testis, TTLL5-mediated α-tubulin polyglutamylation is essential for axonemal doublet stability and progressive sperm motility, and its disruption causes male infertility [PMID:23558686]; in the retina, TTLL5 localizes to photoreceptor basal bodies and is the sole glutamylase that modifies RPGR(ORF15) via a unique cofactor interaction domain, with loss of this activity causing cone opsin mislocalization and photoreceptor degeneration [PMID:27162334]. Biallelic loss-of-function mutations in TTLL5 cause cone-rod and macular dystrophies in humans, with truncating alleles additionally impairing male fertility [PMID:24791901, PMID:28173158]. TTLL5 also functions as a transcriptional comodulator in glucocorticoid receptor signaling, forming a ternary complex with TIF2/SRC-1 coactivators to independently tune induction amplitude, EC50, and partial agonist activity of GR target genes [PMID:17116691, PMID:22342989].\",\n  \"teleology\": [\n    {\n      \"year\": 2006,\n      \"claim\": \"The discovery that TTLL5 (STAMP) associates with TIF2/SRC-1 and modulates glucocorticoid receptor-mediated gene induction and repression established a previously unknown transcriptional comodulator function for this protein, independent of its later-recognized enzymatic activity.\",\n      \"evidence\": \"Co-IP, ChIP on endogenous GR target promoters, siRNA knockdown with endogenous gene readouts, and reporter assays in mammalian cells\",\n      \"pmids\": [\"17116691\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether the transcriptional function depends on TTLL5 enzymatic (glutamylase) activity is unknown\",\n        \"The structural basis for TIF2–STAMP interaction is not resolved\",\n        \"Whether this comodulator role operates in vivo in relevant tissues has not been tested\"\n      ]\n    },\n    {\n      \"year\": 2012,\n      \"claim\": \"Domain-dissection of the GR–TIF2–STAMP ternary complex revealed that distinct regions of each protein independently control different dose-response parameters (Amax, EC50, partial agonist activity), establishing that TTLL5 contributes to fine-tuning of transcriptional output rather than simple on/off regulation.\",\n      \"evidence\": \"Systematic transfection of 25 domain-fragment combinations with reporter and endogenous gene induction assays\",\n      \"pmids\": [\"22342989\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"Mapping relies on overexpressed fragments without validation of endogenous domain requirements\",\n        \"Whether these parameters are modulated at endogenous loci genome-wide is untested\"\n      ]\n    },\n    {\n      \"year\": 2013,\n      \"claim\": \"Generation of Ttll5-knockout mice demonstrated that TTLL5 is the principal α-tubulin polyglutamylase in sperm flagella, with its loss causing axonemal disassembly, immotile sperm, and male infertility — establishing the first in vivo enzymatic function of TTLL5.\",\n      \"evidence\": \"Targeted gene deletion in mice, electron microscopy of sperm axonemes, α-tubulin polyglutamylation assays, fertility tests\",\n      \"pmids\": [\"23558686\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"Whether other TTLLs partially compensate in non-testicular tissues was not addressed\",\n        \"The mechanism by which polyglutamylation stabilizes axonemal doublets is not defined\"\n      ]\n    },\n    {\n      \"year\": 2014,\n      \"claim\": \"Identification of biallelic TTLL5 mutations in patients with cone and macular dystrophies, combined with immunolocalization of TTLL5 to photoreceptor basal bodies, linked the enzyme's glutamylase activity to human retinal disease for the first time.\",\n      \"evidence\": \"Exome and Sanger sequencing of patient cohorts; immunolocalization in human and murine retinal sections\",\n      \"pmids\": [\"24791901\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"No biochemical demonstration that the identified variants impair enzymatic activity was provided in this study\",\n        \"The relevant substrate in photoreceptors was not identified\"\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Identification of RPGR(ORF15) as the critical TTLL5 substrate in photoreceptors — recruited via its C-terminal basic domain binding a TTLL5-specific cofactor interaction domain — unified the retinal and ciliary phenotypes by showing that TTLL5 loss abolishes RPGR glutamylation and phenocopies RPGR-null retinal degeneration, while human disease-causing TTLL5 mutations impair this modification.\",\n      \"evidence\": \"Co-IP in cells, Ttll5-mutant mouse with electrophysiology and opsin localization, mutagenesis of disease alleles with glutamylation assays\",\n      \"pmids\": [\"27162334\"],\n      \"confidence\": \"High\",\n      \"gaps\": [\n        \"How RPGR glutamylation mechanistically supports photoreceptor protein trafficking is not established\",\n        \"Whether additional non-tubulin substrates exist beyond RPGR(ORF15) is unknown\"\n      ]\n    },\n    {\n      \"year\": 2016,\n      \"claim\": \"Clinical delineation of an allele-specific TTLL5 syndrome — truncating variants causing both retinopathy and male infertility while missense variants cause retinopathy alone — established genotype-phenotype correlations consistent with differential sensitivity of tubulin versus RPGR glutamylation to residual enzyme activity.\",\n      \"evidence\": \"NGS and autozygome screening in patient families; immunofluorescence on human sperm and rat retina; sperm motility assays\",\n      \"pmids\": [\"28173158\"],\n      \"confidence\": \"Medium\",\n      \"gaps\": [\n        \"The biochemical basis for why missense variants spare sperm function but not retinal function is not resolved\",\n        \"Cohort sizes remain small for definitive genotype-phenotype rules\"\n      ]\n    },\n    {\n      \"year\": null,\n      \"claim\": \"Key unresolved questions include the structural basis for TTLL5 substrate selectivity between tubulin and RPGR(ORF15), the relationship between its enzymatic and transcriptional comodulator activities, and whether additional non-tubulin substrates contribute to its ciliary or other functions.\",\n      \"evidence\": \"\",\n      \"pmids\": [],\n      \"confidence\": \"Low\",\n      \"gaps\": [\n        \"No crystal or cryo-EM structure of TTLL5 is available\",\n        \"Whether the glutamylase catalytic activity is required for the GR comodulator function has never been tested\",\n        \"A comprehensive substrate profiling of TTLL5 in vivo has not been performed\"\n      ]\n    }\n  ],\n  \"mechanism_profile\": {\n    \"molecular_activity\": [\n      {\"term_id\": \"GO:0016874\", \"supporting_discovery_ids\": [0, 1]},\n      {\"term_id\": \"GO:0140110\", \"supporting_discovery_ids\": [4, 5]}\n    ],\n    \"localization\": [\n      {\"term_id\": \"GO:0005815\", \"supporting_discovery_ids\": [2, 3]},\n      {\"term_id\": \"GO:0005929\", \"supporting_discovery_ids\": [1, 2, 3]},\n      {\"term_id\": \"GO:0005634\", \"supporting_discovery_ids\": [4]}\n    ],\n    \"pathway\": [\n      {\"term_id\": \"R-HSA-162582\", \"supporting_discovery_ids\": [4, 5]},\n      {\"term_id\": \"R-HSA-392499\", \"supporting_discovery_ids\": [0, 1]}\n    ],\n    \"complexes\": [\n      \"GR–TIF2–STAMP ternary complex\"\n    ],\n    \"partners\": [\n      \"RPGR\",\n      \"TIF2\",\n      \"SRC1\",\n      \"NR3C1\"\n    ],\n    \"other_free_text\": []\n  }\n}\n```"}