ADAM10
entrez
102
canonical
uniprot
O14672
canonical
ensembl
ENSG00000137845
resolver
ensp
ENSP00000260408
resolver
ensp
ENSP00000532004
resolver
genesymbol
ADAM10
resolver
genesymbol_syn
KUZ
resolver
genesymbol_syn
MADM
resolver
hgnc
HGNC:188
resolver
uniprot
B4DU28
resolver
uniprot
Q10742
resolver
uniprot
Q92650
resolver
uniprot_entry
ADA10_HUMAN
resolver
uniprot_sec
B4DU28
resolver
uniprot_sec
Q10742
resolver
uniprot_sec
Q92650
resolver
activity_regulation
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 (PubMed:29224781). {ECO:0000250|UniProtKB:Q10741, ECO:0000269|PubMed:29224781}.
uniprot
proteins
amino_acid_sequence
MVLLRVLILLLSWAAGMGGQYGNPLNKYIRHYEGLSYNVDSLHQKHQRAKRAVSHEDQFLRLDFHAHGRHFNLRMKRDTSLFSDEFKVETSNKVLDYDTSHIYTGHIYGEEGSFSHGSVIDGRFEGFIQTRGGTFYVEPAERYIKDRTLPFHSVIYHEDDINYPHKYGPQGGCADHSVFERMRKYQMTGVEEVTQIPQEEHAANGPELLRKKRTTSAEKNTCQLYIQTDHLFFKYYGTREAVIAQISSHVKAIDTIYQTTDFSGIRNISFMVKRIRINTTADEKDPTNPFRFPNIGVEKFLELNSEQNHDDYCLAYVFTDRDFDDGVLGLAWVGAPSGSSGGICEKSKLYSDGKKKSLNTGIITVQNYGSHVPPKVSHITFAHEVGHNFGSPHDSGTECTPGESKNLGQKENGNYIMYARATSGDKLNNNKFSLCSIRNISQVLEKKRNNCFVESGQPICGNGMVEQGEECDCGYSDQCKDECCFDANQPEGRKCKLKPGKQCSPSQGPCCTAQCAFKSKSEKCRDDSDCAREGICNGFTALCPASDPKPNFTDCNRHTQVCINGQCAGSICEKYGLEECTCASSDGKDDKELCHVCCMKKMDPSTCASTGSVQWSRHFSGRTITLQPGSPCNDFRGYCDVFMRCRLVDADGPLARLKKAIFSPELYENIAEWIVAHWWAVLLMGIALIMLMAGFIKICSVHTPSSNPKLPPPKPLPGTLKRRRPPQPIQQPQRQRPRESYQMGHMRR
uniprot
proteins
disease_involvement
DISEASE: Reticulate acropigmentation of Kitamura (RAK) [MIM:615537]: A rare cutaneous pigmentation disorder characterized by reticulate, slightly depressed, sharply demarcated brown macules without hypopigmentation, affecting the dorsa of the hands and feet and appearing in the first or second decade of life. The macules gradually darken and extend to the proximal regions of the extremities. The manifestations tend to progress until middle age, after which progression of the eruptions stops. The pigmentary augmentation is found on the flexor aspects of the wrists, neck, patella and olecranon. Other features include breaks in the epidermal ridges on the palms and fingers, palmoplantar pits, occasionally plantar keratoderma, and partial alopecia. {ECO:0000269|PubMed:23666529}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Alzheimer disease 18 (AD18) [MIM:615590]: A late-onset form of Alzheimer disease. Alzheimer disease is a neurodegenerative disorder characterized by progressive dementia, loss of cognitive abilities, and deposition of fibrillar amyloid proteins as intraneuronal neurofibrillary tangles, extracellular amyloid plaques and vascular amyloid deposits. The major constituents of these plaques are neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that are produced by the proteolysis of the transmembrane APP protein. The cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, such as C31, are also implicated in neuronal death. {ECO:0000269|PubMed:19608551, ECO:0000269|PubMed:24055016}. Note=Disease susceptibility is associated with variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
3.4.24.81
uniprot
proteins
function
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 (PubMed:11786905, PubMed:12475894, PubMed:20592283, PubMed:24990881, PubMed:26686862, PubMed:28600292, PubMed:31792032, PubMed:31792032). Associates with six members of the tetraspanin superfamily TspanC8 which regulate its exit from the endoplasmic reticulum and its substrate selectivity (PubMed:26686862, PubMed:28600292, PubMed:31792032, PubMed:34739841, PubMed:37516108). 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 (PubMed:20592283). 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) (PubMed:11786905, PubMed:26686862, PubMed:29224781, PubMed:34739841, PubMed:33731436). Contributes to the normal cleavage of the cellular prion protein (PubMed:11477090). Involved in the cleavage of the adhesion molecule L1 at the cell surface and in released membrane vesicles, suggesting a vesicle-based protease activity (PubMed:12475894). 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 (PubMed:17557115). Also cleaves the ectodomain of the integral membrane proteins CORIN and ITM2B (PubMed:19114711, PubMed:21288900). 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 (PubMed:26876177). Enhances the cleavage of CHL1 by BACE1 (By similarity). Cleaves NRCAM (By similarity). Cleaves TREM2, resulting in shedding of the TREM2 ectodomain (PubMed:24990881). 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 (PubMed:16239146). Regulates leukocyte transmigration as a sheddase for the adherens junction protein VE-cadherin/CDH5 in endothelial cells (PubMed:28600292). {ECO:0000250|UniProtKB:O35598, ECO:0000269|PubMed:11477090, ECO:0000269|PubMed:11786905, ECO:0000269|PubMed:12475894, ECO:0000269|PubMed:16239146, ECO:0000269|PubMed:17557115, ECO:0000269|PubMed:19114711, ECO:0000269|PubMed:20592283, ECO:0000269|PubMed:21288900, ECO:0000269|PubMed:24990881, ECO:0000269|PubMed:26686862, ECO:0000269|PubMed:26876177, ECO:0000269|PubMed:28600292, ECO:0000269|PubMed:29224781, ECO:0000269|PubMed:31792032, ECO:0000269|PubMed:33731436, ECO:0000269|PubMed:34739841, ECO:0000269|PubMed:37516108}.; FUNCTION: (Microbial infection) Promotes the cytotoxic activity of S.aureus hly by binding to the toxin at zonula adherens and promoting formation of toxin pores. {ECO:0000269|PubMed:20624979, ECO:0000269|PubMed:30463011}.
uniprot
proteins
mass_dalton
84142
uniprot
proteins
mutagenesis
MUTAGEN 384; /note="E->A: Loss of proteolytic activity. Abrogates APP cleavage. Reduces Notch signaling."; /evidence="ECO:0000269|PubMed:29224781, ECO:0000269|PubMed:29430990"; MUTAGEN 638..646; /note="YCDVFMRCR->ACDVFMRCA: Strongly reduces interaction and ADAM10 maturation."; /evidence="ECO:0000269|PubMed:37516108"; MUTAGEN 638..646; /note="YCDVFMRCR->ECDVFMRCE: Strongly reduces interaction and prevents ADAM10 maturation."; /evidence="ECO:0000269|PubMed:37516108"; MUTAGEN 653..656; /note="PLAR->AAAA: Strongly reduces interaction and prevents ADAM10 maturation."; /evidence="ECO:0000269|PubMed:37516108
uniprot
proteins
post_translational_modification
PTM: The precursor is cleaved by furin and PCSK7. {ECO:0000250|UniProtKB:Q10741}.
uniprot
proteins
pubmed
11477090
uniprot
proteins
pubmed
11511685
uniprot
proteins
pubmed
11786905
uniprot
proteins
pubmed
12475894
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
16239146
uniprot
proteins
pubmed
16263699
uniprot
proteins
pubmed
16572171
uniprot
proteins
pubmed
17557115
uniprot
proteins
pubmed
19114711
uniprot
proteins
pubmed
19159218
uniprot
proteins
pubmed
19349973
uniprot
proteins
pubmed
19608551
uniprot
proteins
pubmed
20164177
uniprot
proteins
pubmed
20592283
uniprot
proteins
pubmed
20624979
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21288900
uniprot
proteins
pubmed
21618342
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23666529
uniprot
proteins
pubmed
23676497
uniprot
proteins
pubmed
24055016
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24990881
uniprot
proteins
pubmed
25944712
uniprot
proteins
pubmed
26091039
uniprot
proteins
pubmed
26668317
uniprot
proteins
pubmed
26686862
uniprot
proteins
pubmed
26876177
uniprot
proteins
pubmed
28600292
uniprot
proteins
pubmed
29224781
uniprot
proteins
pubmed
29430990
uniprot
proteins
pubmed
30312582
uniprot
proteins
pubmed
30463011
uniprot
proteins
pubmed
31792032
uniprot
proteins
pubmed
33731436
uniprot
proteins
pubmed
34739841
uniprot
proteins
pubmed
37516108
uniprot
proteins
pubmed
8694785
uniprot
proteins
pubmed
9016778
uniprot
proteins
pubmed
9305925
uniprot
proteins
sequence_length
748
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20624979, ECO:0000269|PubMed:23676497, ECO:0000269|PubMed:24990881, ECO:0000269|PubMed:26686862, ECO:0000269|PubMed:29430990, ECO:0000269|PubMed:30463011, ECO:0000269|PubMed:33731436}; Single-pass type I membrane protein {ECO:0000305}. Golgi apparatus membrane {ECO:0000269|PubMed:12475894}; Single-pass type I membrane protein {ECO:0000305}. Cytoplasmic vesicle, clathrin-coated vesicle {ECO:0000269|PubMed:12475894}. Cell projection, axon {ECO:0000250|UniProtKB:O35598}. Cell projection, dendrite {ECO:0000250|UniProtKB:O35598}. Cell junction, adherens junction {ECO:0000269|PubMed:30463011}. Cytoplasm {ECO:0000269|PubMed:30463011}. Note=Is localized in the plasma membrane but is also expressed in the Golgi apparatus and in clathrin-coated vesicles derived likely from the Golgi (PubMed:12475894). During long term depression, it is recruited to the cell membrane by DLG1 (PubMed:23676497). The immature form is mainly located near cytoplasmic fibrillar structures, while the mature form is predominantly located at zonula adherens and the cell membrane (PubMed:30463011). The localization and clustering of mature ADAM10 to zonula adherens is regulated by AFDN, TSPAN33, PLEKHA7 and PDZD11 (PubMed:30463011). {ECO:0000269|PubMed:12475894, ECO:0000269|PubMed:23676497, ECO:0000269|PubMed:30463011}.
uniprot
proteins
transmembrane_region
TRANSMEM 673..693; /note="Helical"; /evidence="ECO:0000255
uniprot
proteins