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Details on Person UniProt:Q10743 Adam10
| Class:Id | ReferenceGeneProduct:84586 |
|---|---|
| _chainChangeLog | propeptide:-9 added on Fri February 6 2015;chain:10-544 added on Fri February 6 2015 |
| _displayName | UniProt:Q10743 Adam10 |
| _timestamp | 2026-02-20 21:36:48 |
| chain | signal peptide:1-18 propeptide:19-214 chain:215-749 |
| checksum | 7E506394D93A3095 |
| comment | FUNCTION Transmembrane metalloprotease which mediates the ectodomain shedding of a myriad of transmembrane proteins, including adhesion proteins, growth factor precursors and cytokines being essential for development and tissue homeostasis. Associates with six members of the tetraspanin superfamily TspanC8 which regulate its exit from the endoplasmic reticulum and its substrate selectivity (By similarity). Cleaves the membrane-bound precursor of TNF at '76-Ala-|-Val-77' to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface. Responsible for the proteolytic release of several other cell-surface proteins, including heparin-binding epidermal growth-like factor, ephrin-A2, CD44, CDH2 and for constitutive and regulated alpha-secretase cleavage of amyloid precursor protein (APP). Contributes to the normal cleavage of the cellular prion protein. Involved in the cleavage of the adhesion molecule L1 at the cell surface and in released membrane vesicles, suggesting a vesicle-based protease activity (By similarity). Also controls the proteolytic processing of Notch and mediates lateral inhibition during neurogenesis (By similarity). Required for the development of type 1 transitional B cells into marginal zone B cells, probably by cleaving Notch (By similarity). Responsible for the FasL ectodomain shedding and for the generation of the remnant ADAM10-processed FasL (FasL APL) transmembrane form. Also cleaves the ectodomain of the integral membrane proteins CORIN and ITM2B (By similarity). Mediates the proteolytic cleavage of LAG3, leading to release the secreted form of LAG3 (By similarity). Mediates the proteolytic cleavage of IL6R and IL11RA, leading to the release of secreted forms of IL6R and IL11RA (By similarity). Enhances the cleavage of CHL1 by BACE1 (By similarity). Cleaves NRCAM (By similarity). Cleaves TREM2, resulting in shedding of the TREM2 ectodomain (By similarity). Involved in the development and maturation of glomerular and coronary vasculature (By similarity). During development of the cochlear organ of Corti, promotes pillar cell separation by forming a ternary complex with CADH1 and EPHA4 and cleaving CADH1 at adherens junctions (By similarity). May regulate the EFNA5-EPHA3 signaling (By similarity). Regulates leukocyte transmigration as a sheddase for the adherens junction protein VE-cadherin/CDH5 in endothelial cells (By similarity).CATALYTIC ACTIVITY Endopeptidase of broad specificity.COFACTOR Binds 1 zinc ion per subunit.ACTIVITY REGULATION Catalytically inactive when the propeptide is intact and associated with the mature enzyme (By similarity). The disintegrin and cysteine-rich regions modulate access of substrates to exerts an inhibitory effect on the cleavage of ADAM10 substrates (By similarity).SUBUNIT Forms a ternary EFNA5-EPHA3-ADAM10 complex mediating EFNA5 extracellular domain shedding by ADAM10 which regulates the EFNA5-EPHA3 complex internalization and function, the cleavage occurs in trans, with ADAM10 and its substrate being on the membranes of opposing cells. Interacts with the clathrin adapter AP2 complex subunits AP2A1, AP2A2, AP2B1, and AP2M1; this interaction facilitates ADAM10 endocytosis from the plasma membrane during long-term potentiation in hippocampal neurons (By similarity). Forms a ternary complex composed of ADAM10, EPHA4 and CADH1; within the complex, ADAM10 cleaves CADH1 which disrupts adherens junctions (By similarity). Interacts with EPHA2 (By similarity). Interacts with NGF in a divalent cation-dependent manner. Interacts with TSPAN14; the interaction promotes ADAM10 maturation and cell surface expression. Interacts with TSPAN5, TSPAN10, TSPAN14, TSPAN15, TSPAN17 and TSPAN33; these interactions regulate ADAM10 substrate specificity, endocytosis and turnover (By similarity). Interacts (via extracellular domain) with TSPAN33 (via extracellular domain) and (via cytoplasmic domain) with AFDN; interaction with TSPAN33 allows the docking of ADAM10 to zonula adherens through a PDZ11-dependent interaction between TSPAN33 and PLEKHA7 while interaction with AFDN locks ADAM10 at zonula adherens (By similarity). Interacts with DLG1; this interaction recruits ADAM10 to the cell membrane during long-term depression in hippocampal neurons (By similarity). Interacts (via extracellular domain) with BACE1 (via extracellular domain) (By similarity). Interacts with FAM171A1 (By similarity).SUBCELLULAR LOCATION Is localized in the plasma membrane but is also expressed in the Golgi apparatus and in clathrin-coated vesicles derived likely from the Golgi (By similarity). During long term depression, it is recruited to the cell membrane by DLG1 (By similarity). The immature form is mainly located near cytoplasmic fibrillar structures, while the mature form is predominantly located at zonula adherens and the cell membrane (By similarity). The localization and clustering of mature ADAM10 to zonula adherens is regulated by AFDN, TSPAN33, PLEKHA7 and PDZD11 (By similarity).TISSUE SPECIFICITY Expressed in brain, kidney, lung, spleen, ovary and testis.DOMAIN The Cys-rich region C-terminal to the disintegrin domain functions as a substrate-recognition module, it recognizes the EFNA5-EPHA3 Complex but not the individual proteins. Both Cys-rich and stalk region are necessary for interaction with TSPAN5, TSPAN10, TSPAN14, TSPAN17, TSPAN33. Stalk region is sufficient for interaction with TSPAN15.DOMAIN The propeptide keeps the metalloprotease in a latent form via a cysteine switch mechanism. This mechanism may be mediated by a highly conserved cysteine (Cys-173) in the propeptide, which interacts and neutralizes the zinc-coordinating HEXGHXXGXXHD catalytic core of the metalloprotease domain. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.PTM The precursor is cleaved by furin and PCSK7. |
| description | recommendedName: Disintegrin and metalloproteinase domain-containing protein 10 shortName: ADAM 10 ecNumber evidence="1"3.4.24.81 alternativeName: Kuzbanian protein homolog alternativeName: Mammalian disintegrin-metalloprotease cdAntigenNameCD156c/cdAntigenName |
| geneName | Adam10 Madm |
| identifier | Q10743 |
| isSequenceChanged | FALSE |
| keyword | Cell junction Cell membrane Cell projection Cleavage on pair of basic residues Cytoplasm Cytoplasmic vesicle Disulfide bond Glycoprotein Golgi apparatus Hydrolase Membrane Metal-binding Metalloprotease Notch signaling pathway Phosphoprotein Protease Reference proteome SH3-binding Signal Transmembrane Transmembrane helix Zinc Zymogen |
| modified | [InstanceEdit:143527] Schmidt, EE, 2004-11-12 07:45:10 [InstanceEdit:217385] Schmidt, EE, 2008-03-27 06:23:53 [InstanceEdit:354386] Schmidt, EE, 2008-06-18 04:45:12 [InstanceEdit:384350] Kanapin, AA, 2008-11-26 14:00:39 [InstanceEdit:392885] Kanapin, AA, 2009-03-09 12:07:18 [InstanceEdit:400710] Schmidt, EE, 2009-03-25 05:33:35 [InstanceEdit:423310] Kanapin, AA [InstanceEdit:435478] Kanapin, AA [InstanceEdit:435871] Kanapin, AA [InstanceEdit:447347] Kanapin, AA [InstanceEdit:525883] Kanapin, AA [InstanceEdit:613449] Kanapin, AA [InstanceEdit:797602] Kanapin, AA [InstanceEdit:937368] Yung, CK [InstanceEdit:1042053] Yung, CK [InstanceEdit:1220657] Yung, CK [InstanceEdit:1300696] Yung, CK [InstanceEdit:1301627] Yung, CK [InstanceEdit:1551960] Weiser, JD [InstanceEdit:1995863] Weiser, JD [InstanceEdit:2132304] Weiser, JD [InstanceEdit:2265580] Weiser, JD [InstanceEdit:5433710] Weiser, JD [InstanceEdit:5618415] Weiser, JD [InstanceEdit:5634237] Weiser, JD [InstanceEdit:5673015] Weiser, JD [InstanceEdit:5691543] Weiser, JD [InstanceEdit:8944791] Weiser, JD [InstanceEdit:9037114] Weiser, JD [InstanceEdit:9616384] Weiser, JD [InstanceEdit:9627708] Weiser, JD [InstanceEdit:9637257] Weiser, JD [InstanceEdit:9645058] Weiser, JD [InstanceEdit:9657908] Weiser, JD [InstanceEdit:9676415] Weiser, JD [InstanceEdit:9698430] Weiser, JD [InstanceEdit:9730071] Weiser, JD [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20 |
| name | Adam10 |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| secondaryIdentifier | ADA10_RAT A0A0G2K562 |
| sequenceLength | 749 |
| species | [Species:48895] Rattus norvegicus |
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No pathways have been reviewed or authored by UniProt:Q10743 Adam10 (84586)
