⚠️ CAUTION — trust gate(s) tripped; review before using:
- Possible symbol collision: the narrative's opening names a non-human context ("c. elegans") despite a human record — verify the narrative describes human ADAMTSL3 and not a same-symbol protein (cf. the ADA case).
ADAMTSL3 (punctin-2) is a secreted extracellular matrix glycoprotein that functions as a synaptic organizer specifying postsynaptic neurotransmitter receptor domain identity [PMID:14667842, PMID:24896188]. It is built from thrombospondin type 1 repeats, a cysteine-rich domain, a cysteine-free spacer, and immunoglobulin-like repeats, and notably lacks both the protease and disintegrin-like domains found in catalytically active ADAMTS proteins; in transfected cells it is processed to a 210-kDa glycoprotein deposited in the ECM PMID:14667842. Its synaptic role is conserved: the C. elegans orthologue Ce-Punctin/madd-4 is neurally secreted and dictates whether postsynaptic NMJ domains adopt excitatory (acetylcholine receptor) or inhibitory (GABA-A receptor) identity, with distinct isoforms localizing to and patterning cholinergic versus GABAergic synapses PMID:24896188. In the mammalian hippocampus, Adamtsl3 organizes synapses by acting through the transmembrane receptor DCC: it is required for DCC protein expression and for the density of both glutamatergic and GABAergic synapses, and the Adamtsl3-DCC unit drives activity-dependent adaptation at GABAergic synapses via DCC phosphorylation and Src kinase activation PMID:37572323. Beyond its synaptic and matrix biology, ADAMTSL3 acts as a suppressor of hepatocellular carcinoma cell proliferation in vitro and in vivo PMID:32266537. The biochemical mechanism by which this non-catalytic ECM protein controls DCC receptor levels has not been characterized in the available corpus.
Recorded for reference. The AIGR evaluation found this grounding is coarse (collapses to general parents) and can contradict the narrative — do not import these GO ids directly; re-ground from the narrative + PMIDs.
| Year | Confidence | Finding | PMIDs | Journal |
|---|---|---|---|---|
| 2003 | Medium | ADAMTSL3/punctin-2 is a secreted glycoprotein of 1690 amino acids containing thrombospondin type 1 repeats (TSRs), a cysteine-rich domain, a cysteine-free spacer domain, and immunoglobulin-like repeats, but lacking both a protease domain and a disintegrin-like domain. In transfected COS-7 cells, punctin-2 is expressed as a 210-kDa glycoprotein that localizes to the extracellular matrix. | PMID:14667842 | Matrix biology : journal of the International Society for Matrix Biology |
| 2014 | High | The C. elegans orthologue of mammalian punctin-1 and punctin-2 (Ce-Punctin/madd-4) functions as a neurally secreted synaptic organizer that specifies the excitatory or inhibitory identity of postsynaptic NMJ domains. Deletion of Ce-Punctin causes redistribution of synaptic acetylcholine and GABAA receptors into extrasynaptic clusters while presynaptic boutons remain unaltered. Different isoforms generated by alternative promoters have distinct functions: a short isoform localizes to both excitatory and inhibitory NMJs and its disruption relocalizes GABAA receptors from GABAergic to cholinergic synapses; long isoforms are confined to cholinergic NMJs and their ectopic expression in GABAergic neurons recruits acetylcholine receptors to GABAergic NMJs. | PMID:24896188 | Nature |
| 2023 | High | Adamtsl3 functions as a critical hippocampal synapse organizer by acting through the transmembrane receptor DCC (deleted in colorectal cancer). Early post-natal neuron-specific deletion of Adamtsl3 impairs DCC protein expression, causing reduced density of both glutamatergic and GABAergic synapses. Adult deletion of Adamtsl3 specifically in GABAergic or glutamatergic neurons does not interfere with DCC-Netrin-1 function at glutamatergic synapses but controls DCC signaling at GABAergic synapses. The Adamtsl3-DCC signaling unit is essential for activity-dependent adaptations at GABAergic synapses, involving DCC phosphorylation and Src kinase activation. | PMID:37572323 | Cell reports |
| 2020 | Medium | Knockout of ADAMTSL3 in the human SMMC7721 HCC cell line promotes HCC cell proliferation both in vitro and in vivo (subcutaneous xenograft in nude mice), identifying ADAMTSL3 as a suppressor of HCC proliferation. | PMID:32266537 | Journal of cancer research and clinical oncology |
| 2008 | Low | ADAMTSL-3 expression is increased in optic nerve head astrocytes from donors with primary open-angle glaucoma (POAG) compared to normal astrocytes, and POAG astrocytes with elevated ADAMTSL-3 induced less tube formation by co-cultured endothelial cells, indicating an antiangiogenic role for ADAMTSL-3 in this context. | PMID:18474779 | Archives of ophthalmology (Chicago, Ill. : 1960) |
| 2025 | Low | In a genome-wide germline analysis of CAR-T cell clinical trial patients, ADAMTSL3 was identified as a negative regulator of TGFβ, with putative deleterious variants in ADAMTSL3 enriched in control subjects (non-toxicity group) in both ZUMA-1 and ZUMA-7 trials, suggesting a protective effect mediated through TGFβ regulation. | — | bioRxiv |