ADAM10 encodes a single-pass type I transmembrane zinc metalloprotease of the ADAM family. The mature enzyme acts mainly at the cell surface, Golgi-derived vesicles, synaptic membranes, adherens junctions, and tetraspanin-enriched membrane domains, where it cleaves extracellular juxtamembrane regions of many membrane proteins. Its core roles are membrane-protein ectodomain shedding and alpha-secretase processing, including non-amyloidogenic cleavage of APP, S2 cleavage of Notch receptors, and processing of adhesion molecules, growth-factor and cytokine precursors, immune receptors, and other signaling substrates. ADAM10 localization, maturation, endocytosis, and substrate selectivity are regulated by tetraspanins, clathrin/AP2-dependent trafficking, and substrate-specific adaptor contexts.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004222 metalloendopeptidase activity | IBA GO_REF:0000033 | ACCEPT | Summary: ADAM10 is a zinc-dependent metalloendopeptidase (EC 3.4.24.81) that hydrolyzes peptide bonds in substrate ectodomains via its HEXGHXXGXXHD catalytic motif. Reason: This is ADAM10's core catalytic molecular function; supported by IDA/structure. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: ADAM10 is a single-pass type I membrane protein localized at the plasma membrane, the principal site where it cleaves substrate ectodomains in cis and in trans. Reason: Cell membrane is the primary catalytic compartment; supported by EXP/IDA and structural work. |
| GO:0006509 membrane protein ectodomain proteolysis | IBA GO_REF:0000033 | ACCEPT | Summary: ADAM10's defining process: proteolytic shedding of the ectodomains of numerous transmembrane proteins (L1, cadherins, ephrins, TREM2, cytokine receptors and more). Reason: This is the central biological role of ADAM10; strongly supported (IDA/IMP/IBA). |
| GO:0007219 Notch signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: ADAM10 performs the S2 cleavage of Notch receptors, the obligatory ectodomain-shedding step that licenses gamma-secretase and Notch signal transduction. Reason: Notch S2 cleavage is a canonical, essential ADAM10 function; IBA/ISS-supported. |
| GO:0097060 synaptic membrane | IBA GO_REF:0000033 | ACCEPT | Summary: ADAM10 is enriched at synaptic membranes where it cleaves APP and synaptic adhesion/cadherin substrates, contributing to synapse structure and plasticity. Reason: Synaptic membrane localization is a bona fide functional site; IBA/IDA-supported. |
| GO:0000139 Golgi membrane | IEA GO_REF:0000044 | ACCEPT | Summary: ADAM10 resides in the Golgi apparatus membrane as it traffics through the secretory pathway toward the cell surface. Reason: Golgi membrane localization is part of its biosynthetic transit; EXP-supported. |
| GO:0004222 metalloendopeptidase activity | IEA GO_REF:0000002 | ACCEPT | Summary: ADAM10 is a zinc-dependent metalloendopeptidase (EC 3.4.24.81) that hydrolyzes peptide bonds in substrate ectodomains via its HEXGHXXGXXHD catalytic motif. Reason: This is ADAM10's core catalytic molecular function; supported by IDA/structure. |
| GO:0005737 cytoplasm | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: A cytoplasmic pool of ADAM10 (largely immature enzyme near fibrillar structures) is reported, but cytoplasm is not where the protease acts. Reason: Immature/cytoplasmic pool; not the catalytic compartment. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: ADAM10 is a single-pass type I membrane protein localized at the plasma membrane, the principal site where it cleaves substrate ectodomains in cis and in trans. Reason: Cell membrane is the primary catalytic compartment; supported by EXP/IDA and structural work. |
| GO:0005912 adherens junction | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: ADAM10 is clustered at adherens/zonula adherens junctions via AFDN-TSPAN33-PLEKHA7 docking, positioning it to cleave junctional cadherins like E-/VE-cadherin. Reason: Junctional localization supports specific cadherin shedding; pleiotropic, non-core. |
| GO:0006508 proteolysis | IEA GO_REF:0000002 | ACCEPT | Summary: ADAM10 carries out proteolysis of its membrane-protein substrates, the biological process directly enacted by its metalloendopeptidase activity. Reason: Core process directly reflecting its enzymatic action. |
| GO:0008237 metallopeptidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: ADAM10 hydrolyzes peptide bonds as a zinc-requiring metallopeptidase, the activity underlying all of its ectodomain-shedding events. Reason: Correct parent of its catalytic activity; experimentally supported, core. |
| GO:0030136 clathrin-coated vesicle | IEA GO_REF:0000044 | ACCEPT | Summary: ADAM10 localizes to clathrin-coated vesicles, reflecting AP2-dependent endocytosis that internalizes surface enzyme and regulates its availability. Reason: Clathrin-coated vesicle pool tied to AP2-mediated endocytic regulation. |
| GO:0030424 axon | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: ADAM10 is detected in axons (by similarity to mouse O35598), consistent with neuronal expression but not central to its core sheddase mechanism. Reason: Secondary neuronal localization inferred by similarity; non-core. |
| GO:0030425 dendrite | IEA GO_REF:0000044 | KEEP AS NON CORE | Summary: ADAM10 is found in dendrites, in line with its synaptic roles, but dendritic localization itself is a secondary distribution rather than a core feature. Reason: Secondary neuronal compartment inferred by similarity; non-core. |
| GO:0005515 protein binding | IPI PMID:19587294 Tetraspanin12 regulates ADAM10-dependent cleavage of amyloid... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' captures ADAM10's many IPI interactions (tetraspanins, AP2, substrates) but conveys no specific molecular function. Reason: Uninformative generic MF; specific partner relationships captured elsewhere. |
| GO:0005515 protein binding | IPI PMID:23091066 TspanC8 tetraspanins regulate ADAM10/Kuzbanian trafficking a... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' captures ADAM10's many IPI interactions (tetraspanins, AP2, substrates) but conveys no specific molecular function. Reason: Uninformative generic MF; specific partner relationships captured elsewhere. |
| GO:0005515 protein binding | IPI PMID:23289620 Tetraspanin protein CD9 interacts with metalloprotease CD10 ... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' captures ADAM10's many IPI interactions (tetraspanins, AP2, substrates) but conveys no specific molecular function. Reason: Uninformative generic MF; specific partner relationships captured elsewhere. |
| GO:0005515 protein binding | IPI PMID:25036101 Identification of SH3 domain proteins interacting with the c... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' captures ADAM10's many IPI interactions (tetraspanins, AP2, substrates) but conveys no specific molecular function. Reason: Uninformative generic MF; specific partner relationships captured elsewhere. |
| GO:0005515 protein binding | IPI PMID:26686862 TspanC8 tetraspanins differentially regulate the cleavage of... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' captures ADAM10's many IPI interactions (tetraspanins, AP2, substrates) but conveys no specific molecular function. Reason: Uninformative generic MF; specific partner relationships captured elsewhere. |
| GO:0005515 protein binding | IPI PMID:30538620 Visualization of Alzheimer's Disease Related Ξ±-/Ξ²-/Ξ³-Secreta... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' captures ADAM10's many IPI interactions (tetraspanins, AP2, substrates) but conveys no specific molecular function. Reason: Uninformative generic MF; specific partner relationships captured elsewhere. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' captures ADAM10's many IPI interactions (tetraspanins, AP2, substrates) but conveys no specific molecular function. Reason: Uninformative generic MF; specific partner relationships captured elsewhere. |
| GO:0005515 protein binding | IPI PMID:32900848 Cholesterol sensing by CD81 is important for hepatitis C vir... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' captures ADAM10's many IPI interactions (tetraspanins, AP2, substrates) but conveys no specific molecular function. Reason: Uninformative generic MF; specific partner relationships captured elsewhere. |
| GO:0005515 protein binding | IPI PMID:33961781 Dual proteome-scale networks reveal cell-specific remodeling... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' captures ADAM10's many IPI interactions (tetraspanins, AP2, substrates) but conveys no specific molecular function. Reason: Uninformative generic MF; specific partner relationships captured elsewhere. |
| GO:0005515 protein binding | IPI PMID:40205054 Multimodal cell maps as a foundation for structural and func... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' captures ADAM10's many IPI interactions (tetraspanins, AP2, substrates) but conveys no specific molecular function. Reason: Uninformative generic MF; specific partner relationships captured elsewhere. |
| GO:0001701 in utero embryonic development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ADAM10 is essential for embryonic development (largely through Notch and cadherin substrate cleavage); this is a pleiotropic developmental requirement. Reason: Developmental phenotype downstream of substrate cleavage; non-core. |
| GO:0004175 endopeptidase activity | IEA GO_REF:0000120 | ACCEPT | Summary: ADAM10 acts as an endopeptidase, cleaving internal peptide bonds within the ectodomains of transmembrane substrates such as APP and Notch. Reason: Endopeptidase activity is integral to its sheddase mechanism; IMP/ISS-supported. |
| GO:0006509 membrane protein ectodomain proteolysis | IEA GO_REF:0000107 | ACCEPT | Summary: ADAM10's defining process: proteolytic shedding of the ectodomains of numerous transmembrane proteins (L1, cadherins, ephrins, TREM2, cytokine receptors and more). Reason: This is the central biological role of ADAM10; strongly supported (IDA/IMP/IBA). |
| GO:0007219 Notch signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: ADAM10 performs the S2 cleavage of Notch receptors, the obligatory ectodomain-shedding step that licenses gamma-secretase and Notch signal transduction. Reason: Notch S2 cleavage is a canonical, essential ADAM10 function; IBA/ISS-supported. |
| GO:0008593 regulation of Notch signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: By catalyzing the rate-limiting S2 ectodomain cleavage of Notch, ADAM10 directly regulates the magnitude of Notch pathway activation. Reason: Regulation arises directly from its catalytic Notch cleavage; core. |
| GO:0009986 cell surface | IEA GO_REF:0000107 | ACCEPT | Summary: Mature ADAM10 is displayed at the cell surface where it sheds ectodomains of L1, VE-cadherin, ephrins and other transmembrane substrates. Reason: Cell-surface display is integral to its sheddase role; IDA-supported. |
| GO:0014069 postsynaptic density | IEA GO_REF:0000107 | ACCEPT | Summary: ADAM10 is targeted to the postsynaptic density, where DLG1/AP2-regulated trafficking positions it to cleave synaptic substrates during plasticity. Reason: PSD localization is functionally relevant to its synaptic substrate cleavage. |
| GO:0034332 adherens junction organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: By shedding junctional cadherins (E-/VE-cadherin), ADAM10 remodels adherens junctions, an organizational outcome downstream of substrate cleavage. Reason: Consequence of cadherin shedding; pleiotropic, non-core. |
| GO:0038004 epidermal growth factor receptor ligand maturation | IEA GO_REF:0000107 | ACCEPT | Summary: ADAM10 sheds/matures EGFR-family ligands (e.g. HB-EGF, betacellulin), releasing active growth factor from membrane precursors to enable EGFR signaling. Reason: Ligand-precursor shedding is a direct catalytic role of ADAM10. |
| GO:0046930 pore complex | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ADAM10 is implicated in S.aureus alpha-hemolysin pore complex formation by serving as the toxin receptor, a microbial-infection context distinct from its core proteolysis. Reason: Host-pathogen pore association; non-core component. |
| GO:0046931 pore complex assembly | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: By acting as the receptor for S.aureus alpha-hemolysin and clustering it at cell junctions, ADAM10 promotes assembly of cytolytic toxin pores during infection. Reason: Microbial-infection pore-assembly role; non-core relative to its sheddase function. |
| GO:0070573 metallodipeptidase activity | IEA GO_REF:0000107 | REMOVE | Summary: ADAM10 is an endopeptidase that cleaves internal bonds of large protein ectodomains, not a dipeptidase that removes C-terminal dipeptides from short peptides. Reason: IEA-only; biologically contradicted - ADAM10 is an endopeptidase, not a dipeptidase. |
| GO:0090102 cochlea development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: During organ of Corti development ADAM10 promotes pillar-cell separation by cleaving E-cadherin in an EPHA4 complex; a tissue-specific developmental role. Reason: Organ-specific development downstream of cadherin cleavage; non-core. |
| GO:0097060 synaptic membrane | IEA GO_REF:0000107 | ACCEPT | Summary: ADAM10 is enriched at synaptic membranes where it cleaves APP and synaptic adhesion/cadherin substrates, contributing to synapse structure and plasticity. Reason: Synaptic membrane localization is a bona fide functional site; IBA/IDA-supported. |
| GO:0098696 regulation of neurotransmitter receptor localization to postsynaptic specialization membrane | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Through cleavage of synaptic adhesion substrates, ADAM10 influences neurotransmitter-receptor localization at the postsynaptic membrane during plasticity. Reason: Synaptic receptor-trafficking effect downstream of shedding; non-core. |
| GO:0098978 glutamatergic synapse | IEA GO_REF:0000107 | ACCEPT | Summary: ADAM10 localizes to glutamatergic synapses, where it processes synaptic adhesion molecules and APP and participates in activity-dependent plasticity. Reason: Glutamatergic synapse is a documented functional locale for ADAM10. |
| GO:0099173 postsynapse organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ADAM10 shapes postsynaptic organization by cleaving synaptic adhesion molecules and APP, a neuronal structural outcome of its sheddase activity. Reason: Synaptic structural effect downstream of cleavage; non-core. |
| GO:0099175 regulation of postsynapse organization | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Activity-dependent ADAM10 trafficking and substrate cleavage regulate postsynaptic organization during plasticity, a downstream neuronal process. Reason: Plasticity-linked regulatory role downstream of shedding; non-core. |
| GO:0140249 protein catabolic process at postsynapse | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ADAM10 contributes to proteolytic turnover of postsynaptic substrate proteins, a localized catabolic outcome of its synaptic sheddase activity. Reason: Localized synaptic catabolism downstream of cleavage; non-core. |
| GO:0140448 signaling receptor ligand precursor processing | IEA GO_REF:0000107 | ACCEPT | Summary: ADAM10 processes membrane-bound signaling-ligand precursors (e.g. ephrins, EGFR ligands, Notch ligands) into active soluble or cleaved forms. Reason: Precursor processing is a direct catalytic function generalizing ADAM10's shedding. |
| GO:1901342 regulation of vasculature development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ADAM10 contributes to glomerular and coronary vascular development, a pleiotropic developmental outcome of its sheddase activity on vascular substrates. Reason: Developmental vascular role downstream of shedding; non-core. |
| GO:0022617 extracellular matrix disassembly | TAS Reactome:R-HSA-1474228 | KEEP AS NON CORE | Summary: ADAM10 contributes to ECM remodeling/disassembly (Reactome collagen/ECM degradation), a downstream tissue-level consequence of its sheddase activity. Reason: Pleiotropic ECM-remodeling role; TAS-supported, non-core. |
| GO:0004222 metalloendopeptidase activity | TAS Reactome:R-HSA-4224014 | ACCEPT | Summary: ADAM10 is a zinc-dependent metalloendopeptidase (EC 3.4.24.81) that hydrolyzes peptide bonds in substrate ectodomains via its HEXGHXXGXXHD catalytic motif. Reason: This is ADAM10's core catalytic molecular function; supported by IDA/structure. |
| GO:0004222 metalloendopeptidase activity | ISS GO_REF:0000024 | ACCEPT | Summary: ADAM10 is a zinc-dependent metalloendopeptidase (EC 3.4.24.81) that hydrolyzes peptide bonds in substrate ectodomains via its HEXGHXXGXXHD catalytic motif. Reason: This is ADAM10's core catalytic molecular function; supported by IDA/structure. |
| GO:1902430 negative regulation of amyloid-beta formation | IDA PMID:33731436 GDE2-RECK controls ADAM10 Ξ±-secretase-mediated cleavage of a... | ACCEPT | Summary: By cleaving APP within the Abeta sequence (non-amyloidogenic pathway), ADAM10 directly precludes amyloid-beta peptide generation. Reason: Direct mechanistic consequence of alpha-secretase APP cleavage; IDA-supported, core. |
| GO:0004222 metalloendopeptidase activity | IDA PMID:33731436 GDE2-RECK controls ADAM10 Ξ±-secretase-mediated cleavage of a... | ACCEPT | Summary: ADAM10 is a zinc-dependent metalloendopeptidase (EC 3.4.24.81) that hydrolyzes peptide bonds in substrate ectodomains via its HEXGHXXGXXHD catalytic motif. Reason: This is ADAM10's core catalytic molecular function; supported by IDA/structure. |
| GO:0005886 plasma membrane | IDA PMID:33731436 GDE2-RECK controls ADAM10 Ξ±-secretase-mediated cleavage of a... | ACCEPT | Summary: ADAM10 is a single-pass type I membrane protein localized at the plasma membrane, the principal site where it cleaves substrate ectodomains in cis and in trans. Reason: Cell membrane is the primary catalytic compartment; supported by EXP/IDA and structural work. |
| GO:0042985 negative regulation of amyloid precursor protein biosynthetic process | IDA PMID:33731436 GDE2-RECK controls ADAM10 Ξ±-secretase-mediated cleavage of a... | MODIFY | Summary: The IDA evidence reflects ADAM10 reducing amyloidogenic APP processing/Abeta output via alpha-secretase cleavage, not repression of APP biosynthesis per se. Reason: Annotation conflates catabolic cleavage with biosynthesis; better captured by Abeta-formation/APP catabolic terms. Proposed replacements: negative regulation of amyloid-beta formation |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: ADAM10 is a single-pass type I membrane protein localized at the plasma membrane, the principal site where it cleaves substrate ectodomains in cis and in trans. Reason: Cell membrane is the primary catalytic compartment; supported by EXP/IDA and structural work. |
| GO:0004222 metalloendopeptidase activity | IMP PMID:28164773 Apolipoprotein E-mediated Modulation of ADAM10 in Alzheimer'... | ACCEPT | Summary: ADAM10 is a zinc-dependent metalloendopeptidase (EC 3.4.24.81) that hydrolyzes peptide bonds in substrate ectodomains via its HEXGHXXGXXHD catalytic motif. Reason: This is ADAM10's core catalytic molecular function; supported by IDA/structure. |
| GO:0000139 Golgi membrane | EXP PMID:12475894 ADAM10-mediated cleavage of L1 adhesion molecule at the cell... | ACCEPT | Summary: ADAM10 resides in the Golgi apparatus membrane as it traffics through the secretory pathway toward the cell surface. Reason: Golgi membrane localization is part of its biosynthetic transit; EXP-supported. |
| GO:0005737 cytoplasm | EXP PMID:30463011 A Dock-and-Lock Mechanism Clusters ADAM10 at Cell-Cell Junct... | KEEP AS NON CORE | Summary: A cytoplasmic pool of ADAM10 (largely immature enzyme near fibrillar structures) is reported, but cytoplasm is not where the protease acts. Reason: Immature/cytoplasmic pool; not the catalytic compartment. |
| GO:0005886 plasma membrane | EXP PMID:23676497 Endocytosis of synaptic ADAM10 in neuronal plasticity and Al... | ACCEPT | Summary: ADAM10 is a single-pass type I membrane protein localized at the plasma membrane, the principal site where it cleaves substrate ectodomains in cis and in trans. Reason: Cell membrane is the primary catalytic compartment; supported by EXP/IDA and structural work. |
| GO:0005886 plasma membrane | EXP PMID:24990881 TREM2 mutations implicated in neurodegeneration impair cell ... | ACCEPT | Summary: ADAM10 is a single-pass type I membrane protein localized at the plasma membrane, the principal site where it cleaves substrate ectodomains in cis and in trans. Reason: Cell membrane is the primary catalytic compartment; supported by EXP/IDA and structural work. |
| GO:0005886 plasma membrane | EXP PMID:26686862 TspanC8 tetraspanins differentially regulate the cleavage of... | ACCEPT | Summary: ADAM10 is a single-pass type I membrane protein localized at the plasma membrane, the principal site where it cleaves substrate ectodomains in cis and in trans. Reason: Cell membrane is the primary catalytic compartment; supported by EXP/IDA and structural work. |
| GO:0005886 plasma membrane | EXP PMID:29430990 The metalloprotease ADAM10 (a disintegrin and metalloproteas... | ACCEPT | Summary: ADAM10 is a single-pass type I membrane protein localized at the plasma membrane, the principal site where it cleaves substrate ectodomains in cis and in trans. Reason: Cell membrane is the primary catalytic compartment; supported by EXP/IDA and structural work. |
| GO:0005886 plasma membrane | EXP PMID:30463011 A Dock-and-Lock Mechanism Clusters ADAM10 at Cell-Cell Junct... | ACCEPT | Summary: ADAM10 is a single-pass type I membrane protein localized at the plasma membrane, the principal site where it cleaves substrate ectodomains in cis and in trans. Reason: Cell membrane is the primary catalytic compartment; supported by EXP/IDA and structural work. |
| GO:0004222 metalloendopeptidase activity | IDA PMID:18355445 Ectodomain shedding of TNF-alpha is enhanced by nardilysin v... | ACCEPT | Summary: ADAM10 is a zinc-dependent metalloendopeptidase (EC 3.4.24.81) that hydrolyzes peptide bonds in substrate ectodomains via its HEXGHXXGXXHD catalytic motif. Reason: This is ADAM10's core catalytic molecular function; supported by IDA/structure. |
| GO:0006509 membrane protein ectodomain proteolysis | IDA PMID:18355445 Ectodomain shedding of TNF-alpha is enhanced by nardilysin v... | ACCEPT | Summary: ADAM10's defining process: proteolytic shedding of the ectodomains of numerous transmembrane proteins (L1, cadherins, ephrins, TREM2, cytokine receptors and more). Reason: This is the central biological role of ADAM10; strongly supported (IDA/IMP/IBA). |
| GO:0032760 positive regulation of tumor necrosis factor production | IDA PMID:18355445 Ectodomain shedding of TNF-alpha is enhanced by nardilysin v... | KEEP AS NON CORE | Summary: ADAM10 was originally identified as a pro-TNF-processing enzyme; its sheddase activity can positively influence TNF production/release. Reason: Cytokine-output effect of shedding; non-core relative to general sheddase role. |
| GO:1903265 positive regulation of tumor necrosis factor-mediated signaling pathway | IDA PMID:18355445 Ectodomain shedding of TNF-alpha is enhanced by nardilysin v... | KEEP AS NON CORE | Summary: By releasing soluble TNF and TNF-family/receptor ectodomains, ADAM10 can enhance TNF-mediated signaling, a downstream signaling consequence. Reason: Downstream TNF signaling effect of shedding; non-core. |
| GO:0042803 protein homodimerization activity | IEP PMID:25349418 Membrane-enabled dimerization of the intrinsically disordere... | KEEP AS NON CORE | Summary: ADAM10 can self-associate/homodimerize, which may influence its surface organization, but homodimerization is not its principal molecular function. Reason: Ancillary oligomerization property; non-core. |
| GO:0042803 protein homodimerization activity | IPI PMID:25349418 Membrane-enabled dimerization of the intrinsically disordere... | KEEP AS NON CORE | Summary: ADAM10 can self-associate/homodimerize, which may influence its surface organization, but homodimerization is not its principal molecular function. Reason: Ancillary oligomerization property; non-core. |
| GO:0005515 protein binding | IPI PMID:31792032 TspanC8 tetraspanins differentially regulate ADAM10 endocyto... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' captures ADAM10's many IPI interactions (tetraspanins, AP2, substrates) but conveys no specific molecular function. Reason: Uninformative generic MF; specific partner relationships captured elsewhere. |
| GO:0005515 protein binding | IPI PMID:34739841 Crystal structure of the Tspan15 LEL domain reveals a conser... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' captures ADAM10's many IPI interactions (tetraspanins, AP2, substrates) but conveys no specific molecular function. Reason: Uninformative generic MF; specific partner relationships captured elsewhere. |
| GO:0006509 membrane protein ectodomain proteolysis | IDA PMID:31792032 TspanC8 tetraspanins differentially regulate ADAM10 endocyto... | ACCEPT | Summary: ADAM10's defining process: proteolytic shedding of the ectodomains of numerous transmembrane proteins (L1, cadherins, ephrins, TREM2, cytokine receptors and more). Reason: This is the central biological role of ADAM10; strongly supported (IDA/IMP/IBA). |
| GO:0006509 membrane protein ectodomain proteolysis | IDA PMID:34739841 Crystal structure of the Tspan15 LEL domain reveals a conser... | ACCEPT | Summary: ADAM10's defining process: proteolytic shedding of the ectodomains of numerous transmembrane proteins (L1, cadherins, ephrins, TREM2, cytokine receptors and more). Reason: This is the central biological role of ADAM10; strongly supported (IDA/IMP/IBA). |
| GO:0016485 protein processing | ISS GO_REF:0000024 | ACCEPT | Summary: ADAM10 proteolytically processes diverse substrate proteins, converting transmembrane precursors into cleaved/soluble products. Reason: General proteolytic-processing role directly reflects its activity; ISS-supported. |
| GO:0042987 amyloid precursor protein catabolic process | ISS GO_REF:0000024 | ACCEPT | Summary: ADAM10 is the principal alpha-secretase, cleaving APP within the amyloid-beta region to drive non-amyloidogenic APP catabolism and preclude Abeta generation. Reason: Alpha-secretase APP cleavage is a defining ADAM10 function; IMP/ISS-supported. |
| GO:0004222 metalloendopeptidase activity | IDA PMID:18676862 Tumor-associated MICA is shed by ADAM proteases. | ACCEPT | Summary: ADAM10 is a zinc-dependent metalloendopeptidase (EC 3.4.24.81) that hydrolyzes peptide bonds in substrate ectodomains via its HEXGHXXGXXHD catalytic motif. Reason: This is ADAM10's core catalytic molecular function; supported by IDA/structure. |
| GO:0010629 negative regulation of gene expression | IMP PMID:24530397 Reciprocal effects between microRNA-140-5p and ADAM10 suppre... | KEEP AS NON CORE | Summary: ADAM10 can indirectly modulate gene expression (e.g. via Notch/signaling substrate processing); a distal transcriptional consequence, not a direct activity. Reason: Distal transcriptional effect of signaling cleavage; IMP-supported, non-core. |
| GO:0005515 protein binding | IPI PMID:20624979 Role of a disintegrin and metalloprotease 10 in Staphylococc... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' captures ADAM10's many IPI interactions (tetraspanins, AP2, substrates) but conveys no specific molecular function. Reason: Uninformative generic MF; specific partner relationships captured elsewhere. |
| GO:0005886 plasma membrane | IMP PMID:20624979 Role of a disintegrin and metalloprotease 10 in Staphylococc... | ACCEPT | Summary: ADAM10 is a single-pass type I membrane protein localized at the plasma membrane, the principal site where it cleaves substrate ectodomains in cis and in trans. Reason: Cell membrane is the primary catalytic compartment; supported by EXP/IDA and structural work. |
| GO:0004175 endopeptidase activity | IMP PMID:29430990 The metalloprotease ADAM10 (a disintegrin and metalloproteas... | ACCEPT | Summary: ADAM10 acts as an endopeptidase, cleaving internal peptide bonds within the ectodomains of transmembrane substrates such as APP and Notch. Reason: Endopeptidase activity is integral to its sheddase mechanism; IMP/ISS-supported. |
| GO:0005515 protein binding | IPI PMID:23676497 Endocytosis of synaptic ADAM10 in neuronal plasticity and Al... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' captures ADAM10's many IPI interactions (tetraspanins, AP2, substrates) but conveys no specific molecular function. Reason: Uninformative generic MF; specific partner relationships captured elsewhere. |
| GO:0005515 protein binding | IPI PMID:30463011 A Dock-and-Lock Mechanism Clusters ADAM10 at Cell-Cell Junct... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' captures ADAM10's many IPI interactions (tetraspanins, AP2, substrates) but conveys no specific molecular function. Reason: Uninformative generic MF; specific partner relationships captured elsewhere. |
| GO:0005886 plasma membrane | IMP PMID:28164773 Apolipoprotein E-mediated Modulation of ADAM10 in Alzheimer'... | ACCEPT | Summary: ADAM10 is a single-pass type I membrane protein localized at the plasma membrane, the principal site where it cleaves substrate ectodomains in cis and in trans. Reason: Cell membrane is the primary catalytic compartment; supported by EXP/IDA and structural work. |
| GO:0006509 membrane protein ectodomain proteolysis | IMP PMID:28164773 Apolipoprotein E-mediated Modulation of ADAM10 in Alzheimer'... | ACCEPT | Summary: ADAM10's defining process: proteolytic shedding of the ectodomains of numerous transmembrane proteins (L1, cadherins, ephrins, TREM2, cytokine receptors and more). Reason: This is the central biological role of ADAM10; strongly supported (IDA/IMP/IBA). |
| GO:0006509 membrane protein ectodomain proteolysis | IMP PMID:29430990 The metalloprotease ADAM10 (a disintegrin and metalloproteas... | ACCEPT | Summary: ADAM10's defining process: proteolytic shedding of the ectodomains of numerous transmembrane proteins (L1, cadherins, ephrins, TREM2, cytokine receptors and more). Reason: This is the central biological role of ADAM10; strongly supported (IDA/IMP/IBA). |
| GO:0042987 amyloid precursor protein catabolic process | IMP PMID:28164773 Apolipoprotein E-mediated Modulation of ADAM10 in Alzheimer'... | ACCEPT | Summary: ADAM10 is the principal alpha-secretase, cleaving APP within the amyloid-beta region to drive non-amyloidogenic APP catabolism and preclude Abeta generation. Reason: Alpha-secretase APP cleavage is a defining ADAM10 function; IMP/ISS-supported. |
| GO:0046930 pore complex | IMP PMID:30463011 A Dock-and-Lock Mechanism Clusters ADAM10 at Cell-Cell Junct... | KEEP AS NON CORE | Summary: ADAM10 is implicated in S.aureus alpha-hemolysin pore complex formation by serving as the toxin receptor, a microbial-infection context distinct from its core proteolysis. Reason: Host-pathogen pore association; non-core component. |
| GO:0046931 pore complex assembly | IMP PMID:30463011 A Dock-and-Lock Mechanism Clusters ADAM10 at Cell-Cell Junct... | KEEP AS NON CORE | Summary: By acting as the receptor for S.aureus alpha-hemolysin and clustering it at cell junctions, ADAM10 promotes assembly of cytolytic toxin pores during infection. Reason: Microbial-infection pore-assembly role; non-core relative to its sheddase function. |
| GO:0097060 synaptic membrane | IDA PMID:23676497 Endocytosis of synaptic ADAM10 in neuronal plasticity and Al... | ACCEPT | Summary: ADAM10 is enriched at synaptic membranes where it cleaves APP and synaptic adhesion/cadherin substrates, contributing to synapse structure and plasticity. Reason: Synaptic membrane localization is a bona fide functional site; IBA/IDA-supported. |
| GO:0004175 endopeptidase activity | IMP PMID:24990881 TREM2 mutations implicated in neurodegeneration impair cell ... | ACCEPT | Summary: ADAM10 acts as an endopeptidase, cleaving internal peptide bonds within the ectodomains of transmembrane substrates such as APP and Notch. Reason: Endopeptidase activity is integral to its sheddase mechanism; IMP/ISS-supported. |
| GO:0006509 membrane protein ectodomain proteolysis | IMP PMID:24990881 TREM2 mutations implicated in neurodegeneration impair cell ... | ACCEPT | Summary: ADAM10's defining process: proteolytic shedding of the ectodomains of numerous transmembrane proteins (L1, cadherins, ephrins, TREM2, cytokine receptors and more). Reason: This is the central biological role of ADAM10; strongly supported (IDA/IMP/IBA). |
| GO:0005515 protein binding | IPI PMID:30312582 Astroprincin (FAM171A1, C10orf38): A Regulator of Human Cell... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' captures ADAM10's many IPI interactions (tetraspanins, AP2, substrates) but conveys no specific molecular function. Reason: Uninformative generic MF; specific partner relationships captured elsewhere. |
| GO:0004175 endopeptidase activity | IMP PMID:28855301 TREM2 shedding by cleavage at the H157-S158 bond is accelera... | ACCEPT | Summary: ADAM10 acts as an endopeptidase, cleaving internal peptide bonds within the ectodomains of transmembrane substrates such as APP and Notch. Reason: Endopeptidase activity is integral to its sheddase mechanism; IMP/ISS-supported. |
| GO:0006509 membrane protein ectodomain proteolysis | IMP PMID:28855301 TREM2 shedding by cleavage at the H157-S158 bond is accelera... | ACCEPT | Summary: ADAM10's defining process: proteolytic shedding of the ectodomains of numerous transmembrane proteins (L1, cadherins, ephrins, TREM2, cytokine receptors and more). Reason: This is the central biological role of ADAM10; strongly supported (IDA/IMP/IBA). |
| GO:0005515 protein binding | IPI PMID:17301176 Synapse-associated protein-97 mediates alpha-secretase ADAM1... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' captures ADAM10's many IPI interactions (tetraspanins, AP2, substrates) but conveys no specific molecular function. Reason: Uninformative generic MF; specific partner relationships captured elsewhere. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-8952289 | KEEP AS NON CORE | Summary: Portions of nascent ADAM10 reside in the ER lumen during folding and maturation, an early secretory-pathway step rather than a site of catalysis. Reason: Early biosynthetic compartment; non-core. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-9010074 | KEEP AS NON CORE | Summary: Portions of nascent ADAM10 reside in the ER lumen during folding and maturation, an early secretory-pathway step rather than a site of catalysis. Reason: Early biosynthetic compartment; non-core. |
| GO:0005788 endoplasmic reticulum lumen | TAS Reactome:R-HSA-9010113 | KEEP AS NON CORE | Summary: Portions of nascent ADAM10 reside in the ER lumen during folding and maturation, an early secretory-pathway step rather than a site of catalysis. Reason: Early biosynthetic compartment; non-core. |
| GO:0006509 membrane protein ectodomain proteolysis | IMP PMID:20711474 ADAM10 releases a soluble form of the GPNMB/Osteoactivin ext... | ACCEPT | Summary: ADAM10's defining process: proteolytic shedding of the ectodomains of numerous transmembrane proteins (L1, cadherins, ephrins, TREM2, cytokine receptors and more). Reason: This is the central biological role of ADAM10; strongly supported (IDA/IMP/IBA). |
| GO:0035579 specific granule membrane | TAS Reactome:R-HSA-6799350 | KEEP AS NON CORE | Summary: ADAM10 is annotated to neutrophil specific granule membranes (Reactome neutrophil degranulation), a leukocyte-specific compartment peripheral to its core role. Reason: Granule-membrane pool tied to neutrophil biology; non-core. |
| GO:0070821 tertiary granule membrane | TAS Reactome:R-HSA-6798747 | KEEP AS NON CORE | Summary: ADAM10 is annotated to neutrophil tertiary granule membranes, reflecting its presence in granulocyte degranulation compartments rather than its core sheddase site. Reason: Leukocyte granule compartment; non-core. |
| GO:0006509 membrane protein ectodomain proteolysis | IDA PMID:18355449 Calcium-regulated intramembrane proteolysis of the RAGE rece... | ACCEPT | Summary: ADAM10's defining process: proteolytic shedding of the ectodomains of numerous transmembrane proteins (L1, cadherins, ephrins, TREM2, cytokine receptors and more). Reason: This is the central biological role of ADAM10; strongly supported (IDA/IMP/IBA). |
| GO:0006509 membrane protein ectodomain proteolysis | IDA PMID:18419754 The novel sorting nexin SNX33 interferes with cellular PrP f... | ACCEPT | Summary: ADAM10's defining process: proteolytic shedding of the ectodomains of numerous transmembrane proteins (L1, cadherins, ephrins, TREM2, cytokine receptors and more). Reason: This is the central biological role of ADAM10; strongly supported (IDA/IMP/IBA). |
| GO:0005925 focal adhesion | HDA PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome... | KEEP AS NON CORE | Summary: ADAM10 is detected at focal adhesions (high-throughput data); relevant in the context of S.aureus toxin-induced focal adhesion disruption but not a core site. Reason: HDA-derived secondary localization; non-core. |
| GO:0016020 membrane | HDA PMID:19946888 Defining the membrane proteome of NK cells. | ACCEPT | Summary: ADAM10 is an integral membrane metalloprotease anchored in the lipid bilayer via a single-pass transmembrane segment. Reason: Membrane localization is intrinsic to the type I membrane protein architecture. |
| GO:0009986 cell surface | IDA PMID:23035126 The TspanC8 subgroup of tetraspanins interacts with A disint... | ACCEPT | Summary: Mature ADAM10 is displayed at the cell surface where it sheds ectodomains of L1, VE-cadherin, ephrins and other transmembrane substrates. Reason: Cell-surface display is integral to its sheddase role; IDA-supported. |
| GO:0097197 tetraspanin-enriched microdomain | IDA PMID:23035126 The TspanC8 subgroup of tetraspanins interacts with A disint... | ACCEPT | Summary: Mature ADAM10 partitions into tetraspanin (TspanC8)-enriched microdomains; TspanC8 partners govern its ER exit, surface compartmentalization and substrate selectivity. Reason: TspanC8 microdomain localization is mechanistically central to ADAM10 regulation; IDA-supported. |
| GO:0009986 cell surface | IDA PMID:23091066 TspanC8 tetraspanins regulate ADAM10/Kuzbanian trafficking a... | ACCEPT | Summary: Mature ADAM10 is displayed at the cell surface where it sheds ectodomains of L1, VE-cadherin, ephrins and other transmembrane substrates. Reason: Cell-surface display is integral to its sheddase role; IDA-supported. |
| GO:0097038 perinuclear endoplasmic reticulum | IDA PMID:23091066 TspanC8 tetraspanins regulate ADAM10/Kuzbanian trafficking a... | KEEP AS NON CORE | Summary: Immature ADAM10 accumulates in the perinuclear ER prior to TspanC8-regulated exit and maturation, representing a biosynthetic rather than functional site. Reason: Biosynthetic ER pool; non-core localization. |
| GO:0070062 extracellular exosome | HDA PMID:20458337 MHC class II-associated proteins in B-cell exosomes and pote... | KEEP AS NON CORE | Summary: ADAM10 is detected in extracellular exosomes/released membrane vesicles, a vesicle-associated pool that can carry sheddase activity but is a peripheral distribution. Reason: Vesicle-associated extracellular pool; non-core localization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2220944 | ACCEPT | Summary: ADAM10 is a single-pass type I membrane protein localized at the plasma membrane, the principal site where it cleaves substrate ectodomains in cis and in trans. Reason: Cell membrane is the primary catalytic compartment; supported by EXP/IDA and structural work. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2220976 | ACCEPT | Summary: ADAM10 is a single-pass type I membrane protein localized at the plasma membrane, the principal site where it cleaves substrate ectodomains in cis and in trans. Reason: Cell membrane is the primary catalytic compartment; supported by EXP/IDA and structural work. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2666278 | ACCEPT | Summary: ADAM10 is a single-pass type I membrane protein localized at the plasma membrane, the principal site where it cleaves substrate ectodomains in cis and in trans. Reason: Cell membrane is the primary catalytic compartment; supported by EXP/IDA and structural work. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-2730752 | ACCEPT | Summary: ADAM10 is a single-pass type I membrane protein localized at the plasma membrane, the principal site where it cleaves substrate ectodomains in cis and in trans. Reason: Cell membrane is the primary catalytic compartment; supported by EXP/IDA and structural work. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-4224014 | ACCEPT | Summary: ADAM10 is a single-pass type I membrane protein localized at the plasma membrane, the principal site where it cleaves substrate ectodomains in cis and in trans. Reason: Cell membrane is the primary catalytic compartment; supported by EXP/IDA and structural work. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6798747 | ACCEPT | Summary: ADAM10 is a single-pass type I membrane protein localized at the plasma membrane, the principal site where it cleaves substrate ectodomains in cis and in trans. Reason: Cell membrane is the primary catalytic compartment; supported by EXP/IDA and structural work. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-6799350 | ACCEPT | Summary: ADAM10 is a single-pass type I membrane protein localized at the plasma membrane, the principal site where it cleaves substrate ectodomains in cis and in trans. Reason: Cell membrane is the primary catalytic compartment; supported by EXP/IDA and structural work. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9010034 | ACCEPT | Summary: ADAM10 is a single-pass type I membrane protein localized at the plasma membrane, the principal site where it cleaves substrate ectodomains in cis and in trans. Reason: Cell membrane is the primary catalytic compartment; supported by EXP/IDA and structural work. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9010074 | ACCEPT | Summary: ADAM10 is a single-pass type I membrane protein localized at the plasma membrane, the principal site where it cleaves substrate ectodomains in cis and in trans. Reason: Cell membrane is the primary catalytic compartment; supported by EXP/IDA and structural work. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9013284 | ACCEPT | Summary: ADAM10 is a single-pass type I membrane protein localized at the plasma membrane, the principal site where it cleaves substrate ectodomains in cis and in trans. Reason: Cell membrane is the primary catalytic compartment; supported by EXP/IDA and structural work. |
| GO:0006509 membrane protein ectodomain proteolysis | IMP PMID:18355445 Ectodomain shedding of TNF-alpha is enhanced by nardilysin v... | ACCEPT | Summary: ADAM10's defining process: proteolytic shedding of the ectodomains of numerous transmembrane proteins (L1, cadherins, ephrins, TREM2, cytokine receptors and more). Reason: This is the central biological role of ADAM10; strongly supported (IDA/IMP/IBA). |
| GO:0006509 membrane protein ectodomain proteolysis | IMP PMID:18373975 The role of CXCL16 and its processing metalloproteinases ADA... | ACCEPT | Summary: ADAM10's defining process: proteolytic shedding of the ectodomains of numerous transmembrane proteins (L1, cadherins, ephrins, TREM2, cytokine receptors and more). Reason: This is the central biological role of ADAM10; strongly supported (IDA/IMP/IBA). |
| GO:0006509 membrane protein ectodomain proteolysis | IDA PMID:18676862 Tumor-associated MICA is shed by ADAM proteases. | ACCEPT | Summary: ADAM10's defining process: proteolytic shedding of the ectodomains of numerous transmembrane proteins (L1, cadherins, ephrins, TREM2, cytokine receptors and more). Reason: This is the central biological role of ADAM10; strongly supported (IDA/IMP/IBA). |
| GO:0004222 metalloendopeptidase activity | IMP PMID:19114711 Substrate requirements for SPPL2b-dependent regulated intram... | ACCEPT | Summary: ADAM10 is a zinc-dependent metalloendopeptidase (EC 3.4.24.81) that hydrolyzes peptide bonds in substrate ectodomains via its HEXGHXXGXXHD catalytic motif. Reason: This is ADAM10's core catalytic molecular function; supported by IDA/structure. |
| GO:0006509 membrane protein ectodomain proteolysis | IDA PMID:19114711 Substrate requirements for SPPL2b-dependent regulated intram... | ACCEPT | Summary: ADAM10's defining process: proteolytic shedding of the ectodomains of numerous transmembrane proteins (L1, cadherins, ephrins, TREM2, cytokine receptors and more). Reason: This is the central biological role of ADAM10; strongly supported (IDA/IMP/IBA). |
| GO:0006509 membrane protein ectodomain proteolysis | IDA PMID:17557115 The Fas ligand intracellular domain is released by ADAM10 an... | ACCEPT | Summary: ADAM10's defining process: proteolytic shedding of the ectodomains of numerous transmembrane proteins (L1, cadherins, ephrins, TREM2, cytokine receptors and more). Reason: This is the central biological role of ADAM10; strongly supported (IDA/IMP/IBA). |
| GO:0006509 membrane protein ectodomain proteolysis | IMP PMID:17965014 Regulated intramembrane proteolysis of Bri2 (Itm2b) by ADAM1... | ACCEPT | Summary: ADAM10's defining process: proteolytic shedding of the ectodomains of numerous transmembrane proteins (L1, cadherins, ephrins, TREM2, cytokine receptors and more). Reason: This is the central biological role of ADAM10; strongly supported (IDA/IMP/IBA). |
| GO:0005515 protein binding | IPI PMID:10527948 Evidence for an interaction of the metalloprotease-disintegr... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' captures ADAM10's many IPI interactions (tetraspanins, AP2, substrates) but conveys no specific molecular function. Reason: Uninformative generic MF; specific partner relationships captured elsewhere. |
| GO:0010820 positive regulation of T cell chemotaxis | IMP PMID:18373975 The role of CXCL16 and its processing metalloproteinases ADA... | KEEP AS NON CORE | Summary: By shedding endothelial junctional/adhesion molecules (e.g. VE-cadherin, JAM3), ADAM10 promotes T-cell transmigration and chemotaxis. Reason: Immune migration outcome of substrate cleavage; pleiotropic, non-core. |
| GO:0008284 positive regulation of cell population proliferation | IMP PMID:18373975 The role of CXCL16 and its processing metalloproteinases ADA... | KEEP AS NON CORE | Summary: Through Notch activation and growth-factor ligand release, ADAM10 can promote cell proliferation, a downstream consequence of its proteolysis. Reason: Proliferation effect downstream of substrate cleavage; non-core. |
| GO:0030307 positive regulation of cell growth | IMP PMID:18373975 The role of CXCL16 and its processing metalloproteinases ADA... | KEEP AS NON CORE | Summary: By releasing growth-factor ligands (e.g. EGFR ligands) ADAM10 can promote cell growth, a downstream signaling consequence of its sheddase activity. Reason: Growth-promotion downstream of ligand shedding; IMP-supported, non-core. |
| GO:0030335 positive regulation of cell migration | IMP PMID:18373975 The role of CXCL16 and its processing metalloproteinases ADA... | KEEP AS NON CORE | Summary: ADAM10-mediated cleavage of adhesion molecules and release of motogenic ligands can promote cell migration, a pleiotropic downstream effect. Reason: Migration effect downstream of shedding; non-core. |
| GO:0005515 protein binding | IPI PMID:15280379 ADAM binding protein Eve-1 is required for ectodomain sheddi... | MARK AS OVER ANNOTATED | Summary: Bare 'protein binding' captures ADAM10's many IPI interactions (tetraspanins, AP2, substrates) but conveys no specific molecular function. Reason: Uninformative generic MF; specific partner relationships captured elsewhere. |
| GO:0008237 metallopeptidase activity | IMP PMID:12535668 Putative function of ADAM9, ADAM10, and ADAM17 as APP alpha-... | ACCEPT | Summary: ADAM10 hydrolyzes peptide bonds as a zinc-requiring metallopeptidase, the activity underlying all of its ectodomain-shedding events. Reason: Correct parent of its catalytic activity; experimentally supported, core. |
| GO:0034612 response to tumor necrosis factor | IDA PMID:11831872 Involvement of ADAM9 in multinucleated giant cell formation ... | KEEP AS NON CORE | Summary: ADAM10 activity is modulated within TNF responses, a context-specific cellular response rather than a defining feature of the protease. Reason: Response-to-stimulus annotation; non-core. |
| GO:0042117 monocyte activation | IMP PMID:11831872 Involvement of ADAM9 in multinucleated giant cell formation ... | KEEP AS NON CORE | Summary: ADAM10 influences monocyte activation, an immune-cell process downstream of its shedding of cytokine receptors and adhesion/signaling substrates. Reason: Immune-cell process secondary to sheddase activity; IMP-supported, non-core. |
| GO:0004222 metalloendopeptidase activity | NAS PMID:8694785 Molecular cloning of MADM: a catalytically active mammalian ... | ACCEPT | Summary: ADAM10 is a zinc-dependent metalloendopeptidase (EC 3.4.24.81) that hydrolyzes peptide bonds in substrate ectodomains via its HEXGHXXGXXHD catalytic motif. Reason: This is ADAM10's core catalytic molecular function; supported by IDA/structure. |
| GO:0005178 integrin binding | NAS PMID:8694785 Molecular cloning of MADM: a catalytically active mammalian ... | KEEP AS NON CORE | Summary: ADAM10's disintegrin domain can engage integrins, a binding activity relevant to adhesion modulation but ancillary to its core proteolytic function. Reason: Disintegrin-domain integrin binding is supplementary; NAS-supported, non-core. |
| GO:0007162 negative regulation of cell adhesion | NAS PMID:8694785 Molecular cloning of MADM: a catalytically active mammalian ... | KEEP AS NON CORE | Summary: Cleavage of adhesion molecules (L1, cadherins, JAM3) by ADAM10 reduces cell adhesion, a downstream effect of its ectodomain-shedding activity. Reason: Adhesion modulation is a consequence of shedding; non-core. |
| GO:0007229 integrin-mediated signaling pathway | NAS PMID:8694785 Molecular cloning of MADM: a catalytically active mammalian ... | KEEP AS NON CORE | Summary: Via its disintegrin domain and integrin binding, ADAM10 can engage integrin-mediated signaling, an adhesion-linked process secondary to its core protease role. Reason: Disintegrin/integrin signaling is ancillary; NAS-supported, non-core. |
| GO:0016020 membrane | NAS PMID:8694785 Molecular cloning of MADM: a catalytically active mammalian ... | ACCEPT | Summary: ADAM10 is an integral membrane metalloprotease anchored in the lipid bilayer via a single-pass transmembrane segment. Reason: Membrane localization is intrinsic to the type I membrane protein architecture. |
| GO:0001701 in utero embryonic development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ADAM10 is essential for embryonic development (largely through Notch and cadherin substrate cleavage); this is a pleiotropic developmental requirement. Reason: Developmental phenotype downstream of substrate cleavage; non-core. |
| GO:0007219 Notch signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: ADAM10 performs the S2 cleavage of Notch receptors, the obligatory ectodomain-shedding step that licenses gamma-secretase and Notch signal transduction. Reason: Notch S2 cleavage is a canonical, essential ADAM10 function; IBA/ISS-supported. |
| GO:0051089 constitutive protein ectodomain proteolysis | IDA PMID:12714508 The disintegrin-like metalloproteinase ADAM10 is involved in... | ACCEPT | Summary: ADAM10 mediates constitutive (basal, stimulus-independent) ectodomain shedding of substrates such as prion protein and APP, alongside regulated cleavage. Reason: Constitutive shedding is a documented core mode of ADAM10 action; IDA-supported. |
| GO:0004175 endopeptidase activity | ISS GO_REF:0000024 | ACCEPT | Summary: ADAM10 acts as an endopeptidase, cleaving internal peptide bonds within the ectodomains of transmembrane substrates such as APP and Notch. Reason: Endopeptidase activity is integral to its sheddase mechanism; IMP/ISS-supported. |
| GO:0005794 Golgi apparatus | IDA PMID:12475894 ADAM10-mediated cleavage of L1 adhesion molecule at the cell... | ACCEPT | Summary: ADAM10 transits and is detected in the Golgi apparatus, where prodomain processing by furin/PCSK7 contributes to enzyme maturation before surface delivery. Reason: Golgi localization documented by IDA; part of the maturation/trafficking route. |
| GO:0005798 Golgi-associated vesicle | IDA PMID:12475894 ADAM10-mediated cleavage of L1 adhesion molecule at the cell... | ACCEPT | Summary: ADAM10 is found in Golgi-derived vesicles, consistent with its trafficking through and budding from the Golgi en route to the plasma membrane. Reason: Vesicular Golgi pool documented by IDA in PubMed:12475894. |
| GO:0006509 membrane protein ectodomain proteolysis | IDA PMID:12714508 The disintegrin-like metalloproteinase ADAM10 is involved in... | ACCEPT | Summary: ADAM10's defining process: proteolytic shedding of the ectodomains of numerous transmembrane proteins (L1, cadherins, ephrins, TREM2, cytokine receptors and more). Reason: This is the central biological role of ADAM10; strongly supported (IDA/IMP/IBA). |
| GO:0007162 negative regulation of cell adhesion | IDA PMID:12714508 The disintegrin-like metalloproteinase ADAM10 is involved in... | KEEP AS NON CORE | Summary: Cleavage of adhesion molecules (L1, cadherins, JAM3) by ADAM10 reduces cell adhesion, a downstream effect of its ectodomain-shedding activity. Reason: Adhesion modulation is a consequence of shedding; non-core. |
| GO:0007267 cell-cell signaling | NAS PMID:12714508 The disintegrin-like metalloproteinase ADAM10 is involved in... | KEEP AS NON CORE | Summary: By releasing soluble ligands and cleaving receptors, ADAM10 influences cell-cell signaling; this is a broad downstream readout of its proteolysis. Reason: General signaling consequence; NAS-supported, non-core. |
| GO:0008237 metallopeptidase activity | IDA PMID:12475894 ADAM10-mediated cleavage of L1 adhesion molecule at the cell... | ACCEPT | Summary: ADAM10 hydrolyzes peptide bonds as a zinc-requiring metallopeptidase, the activity underlying all of its ectodomain-shedding events. Reason: Correct parent of its catalytic activity; experimentally supported, core. |
| GO:0009986 cell surface | IDA PMID:12475894 ADAM10-mediated cleavage of L1 adhesion molecule at the cell... | ACCEPT | Summary: Mature ADAM10 is displayed at the cell surface where it sheds ectodomains of L1, VE-cadherin, ephrins and other transmembrane substrates. Reason: Cell-surface display is integral to its sheddase role; IDA-supported. |
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Download this section (compressed HTML)Q: How should ADAM10 substrate selectivity be represented without over-annotating every substrate-specific downstream phenotype as a separate core function?
Suggested experts: ADAM protease experts, GO proteolysis curators
Q: Which ADAM10/tetraspanin complexes determine APP alpha-secretase activity versus Notch, cadherin, immune-receptor, or toxin-related substrate cleavage in vivo?
Suggested experts: tetraspanin biology experts, APP processing experts
Q: Should pathogen-exploitation annotations such as S. aureus alpha-toxin pore formation be segregated from normal evolved ADAM10 sheddase biology in review summaries?
Suggested experts: host-pathogen annotation curators, GO biological process curators
Experiment: Use endogenous tagged ADAM10 with substrate-specific reporters for APP, Notch, cadherin, TREM2, CX3CL1, and TNF-family substrates across defined tetraspanin backgrounds.
Hypothesis: Distinct ADAM10/tetraspanin membrane pools tune substrate choice rather than changing the core metalloprotease activity.
Type: substrate-specific sheddase reporter panel
Experiment: Compare ADAM10 Alzheimer-associated variants for maturation, cell-surface localization, APP alpha-cleavage, Notch S2 cleavage, and tetraspanin binding in human neurons.
Hypothesis: ADAM10 variants linked to Alzheimer risk reduce APP alpha-secretase activity through altered maturation or membrane-compartment localization.
Type: endogenous variant knock-in protease trafficking assay
Experiment: Quantify normal substrate shedding separately from S. aureus alpha-toxin pore formation after perturbing junctional ADAM10 docking factors.
Hypothesis: Junctional docking controls pathogen pore formation and some adhesion substrate cleavage without redefining ADAM10 core function.
Type: junctional localization and pathogen-toxin challenge assay
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