ID ADA10_HUMAN Reviewed; 748 AA. AC O14672; B4DU28; Q10742; Q92650; DT 28-FEB-2003, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 11-NOV-2015, entry version 161. DE RecName: Full=Disintegrin and metalloproteinase domain-containing protein 10; DE Short=ADAM 10; DE EC=3.4.24.81; DE AltName: Full=CDw156; DE AltName: Full=Kuzbanian protein homolog; DE AltName: Full=Mammalian disintegrin-metalloprotease; DE AltName: CD_antigen=CD156c; DE Flags: Precursor; GN Name=ADAM10; Synonyms=KUZ, MADM; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PROTEIN SEQUENCE OF RP 216-237. RX PubMed=9305925; DOI=10.1074/jbc.272.39.24588; RA Rosendahl M.S., Ko S.C., Long D.L., Brewer M.T., Rosenzweig B., RA Hedl E., Anderson L., Pyle S.M., Moreland J., Meyers M.A., Kohno T., RA Lyons D., Lichenstein H.S.; RT "Identification and characterization of a pro-tumor necrosis factor- RT alpha-processing enzyme from the ADAM family of zinc RT metalloproteases."; RL J. Biol. Chem. 272:24588-24593(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 109-748 (ISOFORM 1). RX PubMed=8694785; RA Howard L., Mitchell S., Lu X., Griffiths S., Glynn P.; RT "Molecular cloning of MADM: a catalytically active mammalian RT disintegrin-metalloprotease expressed in various cell types."; RL Biochem. J. 317:45-50(1996). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16572171; DOI=10.1038/nature04601; RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S., RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., RA Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human RT chromosome 15."; RL Nature 440:671-675(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP TISSUE SPECIFICITY. RX PubMed=9016778; DOI=10.1006/bbrc.1996.5957; RA McKie N., Edwards T., Dallas D.J., Houghton A., Stringer B., RA Graham R., Russell G., Croucher P.I.; RT "Expression of members of a novel membrane linked metalloproteinase RT family (ADAM) in human articular chondrocytes."; RL Biochem. Biophys. Res. Commun. 230:335-339(1997). RN [6] RP FUNCTION. RX PubMed=12475894; DOI=10.1096/fj.02-0430fje; RA Gutwein P., Mechtersheimer S., Riedle S., Stoeck A., Gast D., RA Joumaa S., Zentgraf H., Fogel M., Altevogt P.; RT "ADAM10-mediated cleavage of L1 adhesion molecule at the cell surface RT and in released membrane vesicles."; RL FASEB J. 17:292-294(2003). RN [7] RP FUNCTION. RX PubMed=11477090; DOI=10.1074/jbc.M105677200; RA Vincent B., Paitel E., Saftig P., Frobert Y., Hartmann D., RA De Strooper B., Grassi J., Lopez-Perez E., Checler F.; RT "The disintegrins ADAM10 and TACE contribute to the constitutive and RT phorbol ester-regulated normal cleavage of the cellular prion RT protein."; RL J. Biol. Chem. 276:37743-37746(2001). RN [8] RP TISSUE SPECIFICITY. RX PubMed=11511685; DOI=10.1177/002215540104900910; RA Chubinskaya S., Mikhail R., Deutsch A., Tindal M.H.; RT "ADAM-10 protein is present in human articular cartilage primarily in RT the membrane-bound form and is upregulated in osteoarthritis and in RT response to IL-1alpha in bovine nasal cartilage."; RL J. Histochem. Cytochem. 49:1165-1176(2001). RN [9] RP FUNCTION. RX PubMed=11786905; DOI=10.1038/nm0102-41; RA Lemjabbar H., Basbaum C.; RT "Platelet-activating factor receptor and ADAM10 mediate responses to RT Staphylococcus aureus in epithelial cells."; RL Nat. Med. 8:41-46(2002). RN [10] RP IDENTIFICATION IN A COMPLEX WITH EFNA5 AND EPHA3, AND FUNCTION IN RP EFNA5-EPHA3 SIGNALING. RX PubMed=16239146; DOI=10.1016/j.cell.2005.08.014; RA Janes P.W., Saha N., Barton W.A., Kolev M.V., Wimmer-Kleikamp S.H., RA Nievergall E., Blobel C.P., Himanen J.P., Lackmann M., Nikolov D.B.; RT "Adam meets Eph: an ADAM substrate recognition module acts as a RT molecular switch for ephrin cleavage in trans."; RL Cell 123:291-304(2005). RN [11] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-278. RC TISSUE=Platelet; RX PubMed=16263699; DOI=10.1074/mcp.M500324-MCP200; RA Lewandrowski U., Moebius J., Walter U., Sickmann A.; RT "Elucidation of N-glycosylation sites on human platelet proteins: a RT glycoproteomic approach."; RL Mol. Cell. Proteomics 5:226-233(2006). RN [12] RP FUNCTION IN CLEAVAGE OF FASLG. RX PubMed=17557115; DOI=10.1038/sj.cdd.4402175; RA Kirkin V., Cahuzac N., Guardiola-Serrano F., Huault S., Luckerath K., RA Friedmann E., Novac N., Wels W.S., Martoglio B., Hueber A.O., RA Zornig M.; RT "The Fas ligand intracellular domain is released by ADAM10 and SPPL2a RT cleavage in T-cells."; RL Cell Death Differ. 14:1678-1687(2007). RN [13] RP FUNCTION IN CLEAVAGE OF ITM2B. RX PubMed=19114711; DOI=10.1074/jbc.M807485200; RA Martin L., Fluhrer R., Haass C.; RT "Substrate requirements for SPPL2b-dependent regulated intramembrane RT proteolysis."; RL J. Biol. Chem. 284:5662-5670(2009). RN [14] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-278. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of RT multiple enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [15] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-278. RC TISSUE=Leukemic T-cell; RX PubMed=19349973; DOI=10.1038/nbt.1532; RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., RA Schiess R., Aebersold R., Watts J.D.; RT "Mass-spectrometric identification and relative quantification of N- RT linked cell surface glycoproteins."; RL Nat. Biotechnol. 27:378-386(2009). RN [16] RP INTERACTION WITH NGF. RX PubMed=20164177; DOI=10.1074/jbc.M110.100479; RA Wijeyewickrema L.C., Gardiner E.E., Gladigau E.L., Berndt M.C., RA Andrews R.K.; RT "Nerve growth factor inhibits metalloproteinase-disintegrins and RT blocks ectodomain shedding of platelet glycoprotein VI."; RL J. Biol. Chem. 285:11793-11799(2010). RN [17] RP FUNCTION IN CLEAVAGE OF JAM3. RX PubMed=20592283; DOI=10.4049/jimmunol.1000556; RA Rabquer B.J., Amin M.A., Teegala N., Shaheen M.K., Tsou P.S., RA Ruth J.H., Lesch C.A., Imhof B.A., Koch A.E.; RT "Junctional adhesion molecule-C is a soluble mediator of RT angiogenesis."; RL J. Immunol. 185:1777-1785(2010). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [19] RP FUNCTION IN CLEAVAGE OF CORIN. RX PubMed=21288900; DOI=10.1074/jbc.M110.185082; RA Jiang J., Wu S., Wang W., Chen S., Peng J., Zhang X., Wu Q.; RT "Ectodomain shedding and autocleavage of the cardiac membrane protease RT corin."; RL J. Biol. Chem. 286:10066-10072(2011). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-719, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [21] RP PHOSPHORYLATION AT THR-719. RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028; RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J., RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N., RA Pinna L.A., Pagliarini D.J., Dixon J.E.; RT "A single kinase generates the majority of the secreted RT phosphoproteome."; RL Cell 161:1619-1632(2015). RN [22] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., RA Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [23] RP VARIANTS AD18 HIS-170 AND GLY-181, AND CHARACTERIZATION OF VARIANTS RP AD18 HIS-170 AND GLY-181. RX PubMed=19608551; DOI=10.1093/hmg/ddp323; RA Kim M., Suh J., Romano D., Truong M.H., Mullin K., Hooli B., RA Norton D., Tesco G., Elliott K., Wagner S.L., Moir R.D., Becker K.D., RA Tanzi R.E.; RT "Potential late-onset Alzheimer's disease-associated mutations in the RT ADAM10 gene attenuate {alpha}-secretase activity."; RL Hum. Mol. Genet. 18:3987-3996(2009). RN [24] RP VARIANT TYR-176. RX PubMed=21618342; DOI=10.1002/humu.21477; RA Wei X., Moncada-Pazos A., Cal S., Soria-Valles C., Gartner J., RA Rudloff U., Lin J.C., Rosenberg S.A., Lopez-Otin C., Samuels Y.; RT "Analysis of the disintegrin-metalloproteinases family reveals ADAM29 RT and ADAM7 are often mutated in melanoma."; RL Hum. Mutat. 32:E2148-E2175(2011). RN [25] RP VARIANTS RAK SER-139 AND TYR-524. RX PubMed=23666529; DOI=10.1093/hmg/ddt207; RA Kono M., Sugiura K., Suganuma M., Hayashi M., Takama H., Suzuki T., RA Matsunaga K., Tomita Y., Akiyama M.; RT "Whole-exome sequencing identifies ADAM10 mutations as a cause of RT reticulate acropigmentation of Kitamura, a clinical entity distinct RT from Dowling-Degos disease."; RL Hum. Mol. Genet. 22:3524-3533(2013). RN [26] RP CHARACTERIZATION OF VARIANTS AD18 HIS-170 AND GLY-181. RX PubMed=24055016; DOI=10.1016/j.neuron.2013.08.035; RA Suh J., Choi S.H., Romano D.M., Gannon M.A., Lesinski A.N., Kim D.Y., RA Tanzi R.E.; RT "ADAM10 missense mutations potentiate beta-amyloid accumulation by RT impairing prodomain chaperone function."; RL Neuron 80:385-401(2013). CC -!- FUNCTION: Cleaves the membrane-bound precursor of TNF-alpha at CC '76-Ala-|-Val-77' to its mature soluble form. Responsible for the CC proteolytical release of soluble JAM3 from endothelial cells CC surface. Responsible for the proteolytic release of several other CC cell-surface proteins, including heparin-binding epidermal growth- CC like factor, ephrin-A2 and for constitutive and regulated alpha- CC secretase cleavage of amyloid precursor protein (APP). Contributes CC to the normal cleavage of the cellular prion protein. Involved in CC the cleavage of the adhesion molecule L1 at the cell surface and CC in released membrane vesicles, suggesting a vesicle-based protease CC activity. Controls also the proteolytic processing of Notch and CC mediates lateral inhibition during neurogenesis. Responsible for CC the FasL ectodomain shedding and for the generation of the remnant CC ADAM10-processed FasL (FasL APL) transmembrane form. Also cleaves CC the ectodomain of the integral membrane proteins CORIN and ITM2B. CC May regulate the EFNA5-EPHA3 signaling. CC {ECO:0000269|PubMed:11477090, ECO:0000269|PubMed:11786905, CC ECO:0000269|PubMed:12475894, ECO:0000269|PubMed:16239146, CC ECO:0000269|PubMed:17557115, ECO:0000269|PubMed:19114711, CC ECO:0000269|PubMed:20592283, ECO:0000269|PubMed:21288900}. CC -!- CATALYTIC ACTIVITY: Endopeptidase of broad specificity. CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250}; CC Note=Binds 1 zinc ion. {ECO:0000250}; CC -!- SUBUNIT: Interacts with EPHA2 (By similarity). Forms a ternary CC EFNA5-EPHA3-ADAM10 complex mediating EFNA5 extracellular domain CC shedding by ADAM10 which regulates the EFNA5-EPHA3 complex CC internalization and function, the cleavage occurs in trans, with CC ADAM10 and its substrate being on the membranes of opposing cells. CC Interacts with NGF in a divalent cation-dependent manner. CC {ECO:0000250|UniProtKB:O35598, ECO:0000269|PubMed:16239146, CC ECO:0000269|PubMed:20164177}. CC -!- SUBCELLULAR LOCATION: Cell membrane; Single-pass type I membrane CC protein. Endomembrane system; Single-pass type I membrane protein. CC Note=Is localized in the plasma membrane but is predominantly CC expressed in the Golgi apparatus and in released membrane vesicles CC derived likely from the Golgi. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O14672-1; Sequence=Displayed; CC Name=2; CC IsoId=O14672-2; Sequence=VSP_056401; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Expressed in spleen, lymph node, thymus, CC peripheral blood leukocyte, bone marrow, cartilage, chondrocytes CC and fetal liver. {ECO:0000269|PubMed:11511685, CC ECO:0000269|PubMed:9016778}. CC -!- INDUCTION: In osteoarthritis affected-cartilage. CC -!- DOMAIN: The conserved cysteine present in the cysteine-switch CC motif binds the catalytic zinc ion, thus inhibiting the enzyme. CC The dissociation of the cysteine from the zinc ion upon the CC activation-peptide release activates the enzyme. CC -!- DOMAIN: The Cys-rich region C-terminal to the disintegrin domain CC functions as a substrate-recognition module, it recognizes the CC EFNA5-EPHA3 Complex but not the individual proteins. CC {ECO:0000250}. CC -!- PTM: The precursor is cleaved by a furin endopeptidase. CC {ECO:0000250}. CC -!- DISEASE: Reticulate acropigmentation of Kitamura (RAK) CC [MIM:615537]: A rare cutaneous pigmentation disorder characterized CC by reticulate, slightly depressed, sharply demarcated brown CC macules without hypopigmentation, affecting the dorsa of the hands CC and feet and appearing in the first or second decade of life. The CC macules gradually darken and extend to the proximal regions of the CC extremities. The manifestations tend to progress until middle age, CC after which progression of the eruptions stops. The pigmentary CC augmentation is found on the flexor aspects of the wrists, neck, CC patella and olecranon. Other features include breaks in the CC epidermal ridges on the palms and fingers, palmoplantar pits, CC occasionally plantar keratoderma, and partial alopecia. CC {ECO:0000269|PubMed:23666529}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Alzheimer disease 18 (AD18) [MIM:615590]: A late-onset CC form of Alzheimer disease, a neurodegenerative disorder CC characterized by progressive dementia, loss of cognitive CC abilities, and deposition of fibrillar amyloid proteins as CC intraneuronal neurofibrillary tangles, extracellular amyloid CC plaques and vascular amyloid deposits. The major constituent of CC these plaques is the neurotoxic amyloid-beta-APP 40-42 peptide CC (s), derived proteolytically from the transmembrane precursor CC protein APP by sequential secretase processing. The cytotoxic C- CC terminal fragments (CTFs) and the caspase-cleaved products such as CC C31 derived from APP, are also implicated in neuronal death. CC {ECO:0000269|PubMed:19608551}. Note=Disease susceptibility is CC associated with variations affecting the gene represented in this CC entry. CC -!- SIMILARITY: Contains 1 disintegrin domain. {ECO:0000255|PROSITE- CC ProRule:PRU00068}. CC -!- SIMILARITY: Contains 1 peptidase M12B domain. CC {ECO:0000255|PROSITE-ProRule:PRU00276}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/ADAM10ID44397ch15q21.html"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF009615; AAC51766.1; -; mRNA. DR EMBL; AK300472; BAG62190.1; -; mRNA. DR EMBL; AC018904; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC091046; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; Z48579; CAA88463.1; -; mRNA. DR CCDS; CCDS10167.1; -. [O14672-1] DR RefSeq; NP_001101.1; NM_001110.3. [O14672-1] DR UniGene; Hs.172028; -. DR UniGene; Hs.578508; -. DR UniGene; Hs.745136; -. DR PDB; 1M1I; Model; -; A=207-453. DR PDBsum; 1M1I; -. DR ProteinModelPortal; O14672; -. DR SMR; O14672; 218-646. DR BioGrid; 106616; 19. DR DIP; DIP-39889N; -. DR IntAct; O14672; 5. DR MINT; MINT-5000775; -. DR STRING; 9606.ENSP00000260408; -. DR BindingDB; O14672; -. DR ChEMBL; CHEMBL5028; -. DR GuidetoPHARMACOLOGY; 1658; -. DR MEROPS; M12.210; -. DR PhosphoSite; O14672; -. DR MaxQB; O14672; -. DR PaxDb; O14672; -. DR PRIDE; O14672; -. DR Ensembl; ENST00000260408; ENSP00000260408; ENSG00000137845. [O14672-1] DR GeneID; 102; -. DR KEGG; hsa:102; -. DR UCSC; uc002afd.1; human. [O14672-1] DR CTD; 102; -. DR GeneCards; ADAM10; -. DR HGNC; HGNC:188; ADAM10. DR HPA; CAB001709; -. DR HPA; HPA050670; -. DR MIM; 602192; gene. DR MIM; 615537; phenotype. DR MIM; 615590; phenotype. DR neXtProt; NX_O14672; -. DR Orphanet; 178307; Reticulate acropigmentation of Kitamura. DR PharmGKB; PA24505; -. DR eggNOG; KOG3658; Eukaryota. DR eggNOG; ENOG410XQWB; LUCA. DR GeneTree; ENSGT00670000097974; -. DR HOGENOM; HOG000008148; -. DR HOVERGEN; HBG050455; -. DR InParanoid; O14672; -. DR KO; K06704; -. DR OMA; EGFIQTH; -. DR OrthoDB; EOG7SBNNQ; -. DR PhylomeDB; O14672; -. DR TreeFam; TF352021; -. DR BioCyc; MetaCyc:ENSG00000137845-MONOMER; -. DR BRENDA; 3.4.24.81; 2681. DR Reactome; R-HSA-1442490; Collagen degradation. DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix. DR Reactome; R-HSA-177929; Signaling by EGFR. DR Reactome; R-HSA-1980148; Signaling by NOTCH3. DR Reactome; R-HSA-1980150; Signaling by NOTCH4. DR Reactome; R-HSA-2122948; Activated NOTCH1 Transmits Signal to the Nucleus. DR Reactome; R-HSA-2644606; Constitutive Signaling by NOTCH1 PEST Domain Mutants. DR Reactome; R-HSA-2660826; Constitutive Signaling by NOTCH1 t(7;9)(NOTCH1:M1580_K2555) Translocation Mutant. DR Reactome; R-HSA-2691232; Constitutive Signaling by NOTCH1 HD Domain Mutants. DR Reactome; R-HSA-2894862; Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants. DR Reactome; R-HSA-2979096; NOTCH2 Activation and Transmission of Signal to the Nucleus. DR Reactome; R-HSA-3928665; EPH-ephrin mediated repulsion of cells. DR SignaLink; O14672; -. DR ChiTaRS; ADAM10; human. DR GeneWiki; ADAM10; -. DR GenomeRNAi; 102; -. DR NextBio; 35475079; -. DR PMAP-CutDB; O14672; -. DR PRO; PR:O14672; -. DR Proteomes; UP000005640; Chromosome 15. DR Bgee; O14672; -. DR CleanEx; HS_ADAM10; -. DR ExpressionAtlas; O14672; baseline and differential. DR Genevisible; O14672; HS. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0070062; C:extracellular exosome; IDA:UniProtKB. DR GO; GO:0005925; C:focal adhesion; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0005798; C:Golgi-associated vesicle; IDA:UniProtKB. DR GO; GO:0016021; C:integral component of membrane; NAS:UniProtKB. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0016020; C:membrane; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0097038; C:perinuclear endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl. DR GO; GO:0097197; C:tetraspanin-enriched microdomain; IDA:UniProtKB. DR GO; GO:0004175; F:endopeptidase activity; ISS:UniProtKB. DR GO; GO:0005178; F:integrin binding; NAS:UniProtKB. DR GO; GO:0004222; F:metalloendopeptidase activity; IMP:UniProtKB. DR GO; GO:0008237; F:metallopeptidase activity; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; ISS:UniProtKB. DR GO; GO:0005102; F:receptor binding; NAS:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro. DR GO; GO:0007411; P:axon guidance; TAS:Reactome. DR GO; GO:0007267; P:cell-cell signaling; NAS:UniProtKB. DR GO; GO:0030574; P:collagen catabolic process; TAS:Reactome. DR GO; GO:0051089; P:constitutive protein ectodomain proteolysis; IDA:UniProtKB. DR GO; GO:0048013; P:ephrin receptor signaling pathway; TAS:Reactome. DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; TAS:Reactome. DR GO; GO:0022617; P:extracellular matrix disassembly; TAS:Reactome. DR GO; GO:0030198; P:extracellular matrix organization; TAS:Reactome. DR GO; GO:0001701; P:in utero embryonic development; ISS:UniProtKB. DR GO; GO:0007229; P:integrin-mediated signaling pathway; NAS:UniProtKB. DR GO; GO:0006509; P:membrane protein ectodomain proteolysis; IDA:UniProtKB. DR GO; GO:0042117; P:monocyte activation; IMP:BHF-UCL. DR GO; GO:0007162; P:negative regulation of cell adhesion; IDA:UniProtKB. DR GO; GO:0007220; P:Notch receptor processing; TAS:Reactome. DR GO; GO:0007219; P:Notch signaling pathway; ISS:UniProtKB. DR GO; GO:0051088; P:PMA-inducible membrane protein ectodomain proteolysis; IMP:BHF-UCL. DR GO; GO:0030307; P:positive regulation of cell growth; IMP:BHF-UCL. DR GO; GO:0030335; P:positive regulation of cell migration; IMP:BHF-UCL. DR GO; GO:0008284; P:positive regulation of cell proliferation; IMP:BHF-UCL. DR GO; GO:0010820; P:positive regulation of T cell chemotaxis; IMP:BHF-UCL. DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB. DR GO; GO:0034612; P:response to tumor necrosis factor; IDA:BHF-UCL. DR Gene3D; 3.40.390.10; -; 1. DR Gene3D; 4.10.70.10; -; 1. DR InterPro; IPR027053; ADAM_10. DR InterPro; IPR001762; Disintegrin_dom. DR InterPro; IPR024079; MetalloPept_cat_dom. DR InterPro; IPR001590; Peptidase_M12B. DR InterPro; IPR002870; Peptidase_M12B_N. DR PANTHER; PTHR11905:SF4; PTHR11905:SF4; 1. DR Pfam; PF00200; Disintegrin; 1. DR Pfam; PF01562; Pep_M12B_propep; 1. DR SMART; SM00050; DISIN; 1. DR SUPFAM; SSF57552; SSF57552; 1. DR PROSITE; PS50215; ADAM_MEPRO; 1. DR PROSITE; PS50214; DISINTEGRIN_2; 1. DR PROSITE; PS00142; ZINC_PROTEASE; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Alzheimer disease; Amyloidosis; KW Cell membrane; Cleavage on pair of basic residues; Complete proteome; KW Direct protein sequencing; Disease mutation; Disulfide bond; KW Glycoprotein; Hydrolase; Membrane; Metal-binding; Metalloprotease; KW Neurodegeneration; Notch signaling pathway; Phosphoprotein; KW Polymorphism; Protease; Reference proteome; SH3-binding; Signal; KW Transmembrane; Transmembrane helix; Zinc; Zymogen. FT SIGNAL 1 19 {ECO:0000255}. FT PROPEP 20 213 {ECO:0000250}. FT /FTId=PRO_0000029066. FT CHAIN 214 748 Disintegrin and metalloproteinase domain- FT containing protein 10. FT /FTId=PRO_0000029067. FT TOPO_DOM 20 672 Extracellular. {ECO:0000255}. FT TRANSMEM 673 693 Helical. {ECO:0000255}. FT TOPO_DOM 694 748 Cytoplasmic. {ECO:0000255}. FT DOMAIN 220 456 Peptidase M12B. {ECO:0000255|PROSITE- FT ProRule:PRU00276}. FT DOMAIN 457 551 Disintegrin. {ECO:0000255|PROSITE- FT ProRule:PRU00068}. FT MOTIF 171 178 Cysteine switch. {ECO:0000250}. FT MOTIF 708 715 SH3-binding. {ECO:0000255}. FT MOTIF 722 728 SH3-binding. {ECO:0000255}. FT COMPBIAS 555 673 Cys-rich. FT ACT_SITE 384 384 FT METAL 173 173 Zinc; in inhibited form. {ECO:0000250}. FT METAL 383 383 Zinc; catalytic. FT METAL 387 387 Zinc; catalytic. FT METAL 393 393 Zinc; catalytic. FT MOD_RES 719 719 Phosphothreonine; by FAM20C. FT {ECO:0000244|PubMed:24275569, FT ECO:0000269|PubMed:26091039}. FT CARBOHYD 267 267 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 278 278 N-linked (GlcNAc...). FT {ECO:0000269|PubMed:16263699, FT ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:19349973}. FT CARBOHYD 439 439 N-linked (GlcNAc...). {ECO:0000255}. FT CARBOHYD 551 551 N-linked (GlcNAc...). {ECO:0000255}. FT DISULFID 222 313 {ECO:0000250}. FT DISULFID 344 451 {ECO:0000250}. FT DISULFID 399 435 {ECO:0000250}. FT DISULFID 484 515 {ECO:0000250}. FT DISULFID 503 511 {ECO:0000250}. FT DISULFID 524 543 {ECO:0000250}. FT DISULFID 530 562 {ECO:0000250}. FT DISULFID 555 567 {ECO:0000250}. FT DISULFID 572 598 {ECO:0000250}. FT DISULFID 580 607 {ECO:0000250}. FT DISULFID 582 597 {ECO:0000250}. FT DISULFID 594 639 {ECO:0000250}. FT DISULFID 632 645 {ECO:0000250}. FT VAR_SEQ 19 319 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_056401. FT VARIANT 139 139 P -> S (in RAK). FT {ECO:0000269|PubMed:23666529}. FT /FTId=VAR_070907. FT VARIANT 170 170 Q -> H (in AD18; associated with disease FT susceptibility; significantly attenuates FT alpha-secretase activity of the enzyme; FT shifts APP processing toward beta- FT secretase-mediated cleavage resulting in FT enhanced beta-amyloid plaque load and FT reactive gliosis). FT {ECO:0000269|PubMed:19608551, FT ECO:0000269|PubMed:24055016}. FT /FTId=VAR_070908. FT VARIANT 176 176 H -> Y (in a cutaneous metastatic FT melanoma sample; somatic mutation). FT {ECO:0000269|PubMed:21618342}. FT /FTId=VAR_066309. FT VARIANT 181 181 R -> G (in AD18; associated with disease FT susceptibility; significantly attenuates FT alpha-secretase activity of the enzyme; FT shifts APP processing toward beta- FT secretase-mediated cleavage resulting in FT enhanced beta-amyloid plaque load and FT reactive gliosis). FT {ECO:0000269|PubMed:19608551, FT ECO:0000269|PubMed:24055016}. FT /FTId=VAR_070909. FT VARIANT 524 524 C -> Y (in RAK). FT {ECO:0000269|PubMed:23666529}. FT /FTId=VAR_070910. FT CONFLICT 162 162 N -> SERLKLRLRKLMSLELWTSCCLPCALLLHSWKKAVN FT SHCLYFKDFWGFSEIY (in Ref. 2; CAA88463). FT {ECO:0000305}. FT CONFLICT 212 212 K -> R (in Ref. 2; CAA88463). FT {ECO:0000305}. FT CONFLICT 296 296 G -> S (in Ref. 2; CAA88463). FT {ECO:0000305}. SQ SEQUENCE 748 AA; 84142 MW; 0881E65B17022A71 CRC64; MVLLRVLILL LSWAAGMGGQ YGNPLNKYIR HYEGLSYNVD SLHQKHQRAK RAVSHEDQFL RLDFHAHGRH FNLRMKRDTS LFSDEFKVET SNKVLDYDTS HIYTGHIYGE EGSFSHGSVI DGRFEGFIQT RGGTFYVEPA ERYIKDRTLP FHSVIYHEDD INYPHKYGPQ GGCADHSVFE RMRKYQMTGV EEVTQIPQEE HAANGPELLR KKRTTSAEKN TCQLYIQTDH LFFKYYGTRE AVIAQISSHV KAIDTIYQTT DFSGIRNISF MVKRIRINTT ADEKDPTNPF RFPNIGVEKF LELNSEQNHD DYCLAYVFTD RDFDDGVLGL AWVGAPSGSS GGICEKSKLY SDGKKKSLNT GIITVQNYGS HVPPKVSHIT FAHEVGHNFG SPHDSGTECT PGESKNLGQK ENGNYIMYAR ATSGDKLNNN KFSLCSIRNI SQVLEKKRNN CFVESGQPIC GNGMVEQGEE CDCGYSDQCK DECCFDANQP EGRKCKLKPG KQCSPSQGPC CTAQCAFKSK SEKCRDDSDC AREGICNGFT ALCPASDPKP NFTDCNRHTQ VCINGQCAGS ICEKYGLEEC TCASSDGKDD KELCHVCCMK KMDPSTCAST GSVQWSRHFS GRTITLQPGS PCNDFRGYCD VFMRCRLVDA DGPLARLKKA IFSPELYENI AEWIVAHWWA VLLMGIALIM LMAGFIKICS VHTPSSNPKL PPPKPLPGTL KRRRPPQPIQ QPQRQRPRES YQMGHMRR //