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 27-MAR-2024, entry version 223. DE RecName: Full=Disintegrin and metalloproteinase domain-containing protein 10 {ECO:0000305}; DE Short=ADAM 10; DE EC=3.4.24.81 {ECO:0000269|PubMed:11477090, ECO:0000269|PubMed:12475894, ECO:0000269|PubMed:16239146, ECO:0000269|PubMed:17557115, ECO:0000269|PubMed:19114711, ECO:0000269|PubMed:20592283, ECO:0000269|PubMed:29224781}; 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 {ECO:0000312|HGNC:HGNC:188}; Synonyms=KUZ, MADM; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PROTEIN SEQUENCE OF 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., Hedl E., RA Anderson L., Pyle S.M., Moreland J., Meyers M.A., Kohno T., Lyons D., RA Lichenstein H.S.; RT "Identification and characterization of a pro-tumor necrosis factor-alpha- RT processing enzyme from the ADAM family of zinc metalloproteases."; RL J. Biol. Chem. 272:24588-24593(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 109-748 (ISOFORM 1). RX PubMed=8694785; DOI=10.1042/bj3170045; RA Howard L., Mitchell S., Lu X., Griffiths S., Glynn P.; RT "Molecular cloning of MADM: a catalytically active mammalian disintegrin- RT 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., Fahey J., RA Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., RA Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., RA Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., RA O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., RA Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., RA Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human chromosome RT 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., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., 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., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA 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., Graham R., RA Russell G., Croucher P.I.; RT "Expression of members of a novel membrane linked metalloproteinase family RT (ADAM) in human articular chondrocytes."; RL Biochem. Biophys. Res. Commun. 230:335-339(1997). RN [6] RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION. RX PubMed=12475894; DOI=10.1096/fj.02-0430fje; RA Gutwein P., Mechtersheimer S., Riedle S., Stoeck A., Gast D., Joumaa S., RA Zentgraf H., Fogel M., Altevogt P.; RT "ADAM10-mediated cleavage of L1 adhesion molecule at the cell surface and RT in released membrane vesicles."; RL FASEB J. 17:292-294(2003). RN [7] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=11477090; DOI=10.1074/jbc.m105677200; RA Vincent B., Paitel E., Saftig P., Frobert Y., Hartmann D., De Strooper B., RA 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 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 the RT membrane-bound form and is upregulated in osteoarthritis and in response to RT 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, FUNCTION IN EFNA5-EPHA3 RP SIGNALING, AND CATALYTIC ACTIVITY. 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 molecular RT 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., 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 multiple RT 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-linked RT 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 blocks RT 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., Ruth J.H., RA Lesch C.A., Imhof B.A., Koch A.E.; RT "Junctional adhesion molecule-C is a soluble mediator of angiogenesis."; RL J. Immunol. 185:1777-1785(2010). RN [18] RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH S.AUREUS HLY, AND RP SUBCELLULAR LOCATION. RX PubMed=20624979; DOI=10.1073/pnas.1001815107; RA Wilke G.A., Bubeck Wardenburg J.; RT "Role of a disintegrin and metalloprotease 10 in Staphylococcus aureus RT alpha-hemolysin-mediated cellular injury."; RL Proc. Natl. Acad. Sci. U.S.A. 107:13473-13478(2010). RN [19] 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., Buerckstuemmer T., RA 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 [20] 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 [21] RP INTERACTION WITH AP2A1; AP2A2; AP2B1; AP2M1 AND DLG1, SUBCELLULAR LOCATION, RP AND TISSUE SPECIFICITY. RX PubMed=23676497; DOI=10.1172/jci65401; RA Marcello E., Saraceno C., Musardo S., Vara H., de la Fuente A.G., RA Pelucchi S., Di Marino D., Borroni B., Tramontano A., Perez-Otano I., RA Padovani A., Giustetto M., Gardoni F., Di Luca M.; RT "Endocytosis of synaptic ADAM10 in neuronal plasticity and Alzheimer's RT disease."; RL J. Clin. Invest. 123:2523-2538(2013). RN [22] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-719, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-719, AND IDENTIFICATION BY RP 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., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [24] RP FUNCTION, AND SUBCELLULAR LOCATION. RX PubMed=24990881; DOI=10.1126/scitranslmed.3009093; RA Kleinberger G., Yamanishi Y., Suarez-Calvet M., Czirr E., Lohmann E., RA Cuyvers E., Struyfs H., Pettkus N., Wenninger-Weinzierl A., Mazaheri F., RA Tahirovic S., Lleo A., Alcolea D., Fortea J., Willem M., Lammich S., RA Molinuevo J.L., Sanchez-Valle R., Antonell A., Ramirez A., Heneka M.T., RA Sleegers K., van der Zee J., Martin J.J., Engelborghs S., RA Demirtas-Tatlidede A., Zetterberg H., Van Broeckhoven C., Gurvit H., RA Wyss-Coray T., Hardy J., Colonna M., Haass C.; RT "TREM2 mutations implicated in neurodegeneration impair cell surface RT transport and phagocytosis."; RL Sci. Transl. Med. 6:243RA86-243RA86(2014). RN [25] 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 phosphoproteome."; RL Cell 161:1619-1632(2015). RN [26] 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., Ayoub D., RA 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 [27] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND INTERACTION WITH RP TSPAN5; TSPAN14; TSPAN15 AND TSPAN33. RX PubMed=26686862; DOI=10.1007/s00018-015-2111-z; RA Jouannet S., Saint-Pol J., Fernandez L., Nguyen V., Charrin S., RA Boucheix C., Brou C., Milhiet P.E., Rubinstein E.; RT "TspanC8 tetraspanins differentially regulate the cleavage of ADAM10 RT substrates, Notch activation and ADAM10 membrane compartmentalization."; RL Cell. Mol. Life Sci. 73:1895-1915(2016). RN [28] RP FUNCTION. RX PubMed=26876177; DOI=10.1016/j.celrep.2016.01.053; RA Lokau J., Nitz R., Agthe M., Monhasery N., Aparicio-Siegmund S., RA Schumacher N., Wolf J., Moeller-Hackbarth K., Waetzig G.H., Groetzinger J., RA Mueller-Newen G., Rose-John S., Scheller J., Garbers C.; RT "Proteolytic Cleavage Governs Interleukin-11 Trans-signaling."; RL Cell Rep. 14:1761-1773(2016). RN [29] RP INTERACTION WITH TSPAN14, AND DOMAIN. RX PubMed=26668317; DOI=10.1074/jbc.m115.703058; RA Noy P.J., Yang J., Reyat J.S., Matthews A.L., Charlton A.E., Furmston J., RA Rogers D.A., Rainger G.E., Tomlinson M.G.; RT "TspanC8 tetraspanins and A disintegrin and metalloprotease 10 (ADAM10) RT interact via their extracellular regions: evidence for distinct binding RT mechanisms for different TspanC8 proteins."; RL J. Biol. Chem. 291:3145-3157(2016). RN [30] RP FUNCTION (MICROBIAL INFECTION), INTERACTION WITH TSPAN33 AND AFDN, AND RP SUBCELLULAR LOCATION. RX PubMed=30463011; DOI=10.1016/j.celrep.2018.10.088; RA Shah J., Rouaud F., Guerrera D., Vasileva E., Popov L.M., Kelley W.L., RA Rubinstein E., Carette J.E., Amieva M.R., Citi S.; RT "A Dock-and-Lock Mechanism Clusters ADAM10 at Cell-Cell Junctions to RT Promote alpha-Toxin Cytotoxicity."; RL Cell Rep. 25:2132-2147(2018). RN [31] RP CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, ACTIVE SITE, AND MUTAGENESIS OF RP GLU-384. RX PubMed=29430990; DOI=10.1096/fj.201700823rr; RA Brummer T., Pigoni M., Rossello A., Wang H., Noy P.J., Tomlinson M.G., RA Blobel C.P., Lichtenthaler S.F.; RT "The metalloprotease ADAM10 (a disintegrin and metalloprotease 10) RT undergoes rapid, postlysis autocatalytic degradation."; RL FASEB J. 32:3560-3573(2018). RN [32] RP INTERACTION WITH FAM171A1. RX PubMed=30312582; DOI=10.1016/j.ajpath.2018.09.006; RA Rasila T., Saavalainen O., Attalla H., Lankila P., Haglund C., Hoelttae E., RA Andersson L.C.; RT "Astroprincin (FAM171A1, C10orf38): A Regulator of Human Cell Shape and RT Invasive Growth."; RL Am. J. Pathol. 189:177-189(2019). RN [33] RP FUNCTION, AND INTERACTION WITH TSPAN5 AND TSPAN17. RX PubMed=28600292; DOI=10.4049/jimmunol.1600713; RA Reyat J.S., Chimen M., Noy P.J., Szyroka J., Rainger G.E., Tomlinson M.G.; RT "ADAM10-Interacting Tetraspanins Tspan5 and Tspan17 Regulate VE-Cadherin RT Expression and Promote T Lymphocyte Transmigration."; RL J. Immunol. 199:666-676(2017). RN [34] RP FUNCTION, AND INTERACTION WITH TSPAN5 AND TSPAN15. RX PubMed=31792032; DOI=10.26508/lsa.201900444; RA Eschenbrenner E., Jouannet S., Clay D., Chaker J., Boucheix C., Brou C., RA Tomlinson M.G., Charrin S., Rubinstein E.; RT "TspanC8 tetraspanins differentially regulate ADAM10 endocytosis and half- RT life."; RL Life. Sci Alliance 3:0-0(2020). RN [35] RP FUNCTION, AND INTERACTION WITH TSPAN15. RX PubMed=34739841; DOI=10.1016/j.str.2021.10.007; RA Lipper C.H., Gabriel K.H., Seegar T.C.M., Duerr K.L., Tomlinson M.G., RA Blacklow S.C.; RT "Crystal structure of the Tspan15 LEL domain reveals a conserved ADAM10 RT binding site."; RL Structure 30:206-214.e4(2022). RN [36] {ECO:0007744|PDB:6BDZ, ECO:0007744|PDB:6BE6} RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 214-654 IN COMPLEX WITH ZINC, RP CATALYTIC ACTIVITY, FUNCTION, MUTAGENESIS OF GLU-384, GLYCOSYLATION AT RP ASN-278, DISULFIDE BOND, AND ACTIVE SITE. RX PubMed=29224781; DOI=10.1016/j.cell.2017.11.014; RA Seegar T.C.M., Killingsworth L.B., Saha N., Meyer P.A., Patra D., RA Zimmerman B., Janes P.W., Rubinstein E., Nikolov D.B., Skiniotis G., RA Kruse A.C., Blacklow S.C.; RT "Structural basis for regulated proteolysis by the alpha-secretase RT ADAM10."; RL Cell 171:1638-1648.E7(2017). RN [37] {ECO:0007744|PDB:8ESV} RP STRUCTURE BY ELECTRON MICROSCOPY (3.3 ANGSTROMS) OF 214-748 IN COMPLEX WITH RP TSPAN15 AND ZINC, INTERACTION WITH TSPAN15, FUNCTION, BIOPHYSICOCHEMICAL RP PROPERTIES, CATALYTIC ACTIVITY, DISULFIDE BOND, AND MUTAGENESIS OF RP 638-TYR--ARG-646 AND 653-PRO--ARG-656. RX PubMed=37516108; DOI=10.1016/j.cell.2023.06.026; RA Lipper C.H., Egan E.D., Gabriel K.H., Blacklow S.C.; RT "Structural basis for membrane-proximal proteolysis of substrates by RT ADAM10."; RL Cell 186:3632-3641.e10(2023). RN [38] RP VARIANTS AD18 HIS-170 AND GLY-181, AND CHARACTERIZATION OF VARIANTS AD18 RP 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., Norton D., RA Tesco G., Elliott K., Wagner S.L., Moir R.D., Becker K.D., 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 [39] 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., Rudloff U., RA Lin J.C., Rosenberg S.A., Lopez-Otin C., Samuels Y.; RT "Analysis of the disintegrin-metalloproteinases family reveals ADAM29 and RT ADAM7 are often mutated in melanoma."; RL Hum. Mutat. 32:E2148-E2175(2011). RN [40] 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 from RT Dowling-Degos disease."; RL Hum. Mol. Genet. 22:3524-3533(2013). RN [41] 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: Transmembrane metalloprotease which mediates the ectodomain CC shedding of a myriad of transmembrane proteins, including adhesion CC proteins, growth factor precursors and cytokines being essential for CC development and tissue homeostasis (PubMed:11786905, PubMed:12475894, CC PubMed:20592283, PubMed:24990881, PubMed:26686862, PubMed:28600292, CC PubMed:31792032). Associates with six members of the tetraspanin CC superfamily TspanC8 which regulate its exit from the endoplasmic CC reticulum and its substrate selectivity (PubMed:26686862, CC PubMed:31792032, PubMed:28600292, PubMed:34739841, PubMed:37516108). CC Cleaves the membrane-bound precursor of TNF-alpha at '76-Ala-|-Val-77' CC to its mature soluble form. Responsible for the proteolytical release CC of soluble JAM3 from endothelial cells surface (PubMed:20592283). CC Responsible for the proteolytic release of several other cell-surface CC proteins, including heparin-binding epidermal growth-like factor, CC ephrin-A2, CD44, CDH2 and for constitutive and regulated alpha- CC secretase cleavage of amyloid precursor protein (APP) (PubMed:26686862, CC PubMed:11786905, PubMed:29224781, PubMed:34739841). Contributes to the CC normal cleavage of the cellular prion protein (PubMed:11477090). CC Involved in the cleavage of the adhesion molecule L1 at the cell CC surface and in released membrane vesicles, suggesting a vesicle-based CC protease activity (PubMed:12475894). Controls also the proteolytic CC processing of Notch and mediates lateral inhibition during neurogenesis CC (By similarity). Responsible for the FasL ectodomain shedding and for CC the generation of the remnant ADAM10-processed FasL (FasL APL) CC transmembrane form (PubMed:17557115). Also cleaves the ectodomain of CC the integral membrane proteins CORIN and ITM2B (PubMed:19114711, CC PubMed:21288900). Mediates the proteolytic cleavage of LAG3, leading to CC release the secreted form of LAG3 (By similarity). Mediates the CC proteolytic cleavage of IL6R and IL11RA, leading to the release of CC secreted forms of IL6R and IL11RA (PubMed:26876177). Enhances the CC cleavage of CHL1 by BACE1 (By similarity). Cleaves NRCAM (By CC similarity). Cleaves TREM2, resulting in shedding of the TREM2 CC ectodomain (PubMed:24990881). Involved in the development and CC maturation of glomerular and coronary vasculature (By similarity). CC During development of the cochlear organ of Corti, promotes pillar cell CC separation by forming a ternary complex with CADH1 and EPHA4 and CC cleaving CADH1 at adherens junctions (By similarity). May regulate the CC EFNA5-EPHA3 signaling (PubMed:16239146). Regulates leukocyte CC transmigration as a sheddase for the adherens junction protein VE- CC cadherin/CDH5 in endothelial cells (PubMed:28600292). CC {ECO:0000250|UniProtKB:O35598, ECO:0000269|PubMed:11477090, CC ECO:0000269|PubMed:11786905, ECO:0000269|PubMed:12475894, CC ECO:0000269|PubMed:16239146, ECO:0000269|PubMed:17557115, CC ECO:0000269|PubMed:19114711, ECO:0000269|PubMed:20592283, CC ECO:0000269|PubMed:21288900, ECO:0000269|PubMed:24990881, CC ECO:0000269|PubMed:26686862, ECO:0000269|PubMed:26876177, CC ECO:0000269|PubMed:28600292, ECO:0000269|PubMed:29224781, CC ECO:0000269|PubMed:31792032, ECO:0000269|PubMed:34739841, CC ECO:0000269|PubMed:37516108}. CC -!- FUNCTION: (Microbial infection) Promotes the cytotoxic activity of CC S.aureus hly by binding to the toxin at zonula adherens and promoting CC formation of toxin pores. {ECO:0000269|PubMed:20624979, CC ECO:0000269|PubMed:30463011}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Endopeptidase of broad specificity.; EC=3.4.24.81; CC Evidence={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 ECO:0000269|PubMed:26686862, ECO:0000269|PubMed:29224781, CC ECO:0000269|PubMed:29430990, ECO:0000269|PubMed:37516108, CC ECO:0000305|PubMed:24990881}; CC -!- COFACTOR: CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; CC Evidence={ECO:0000269|PubMed:29224781}; CC Note=Binds 1 zinc ion per subunit. {ECO:0000269|PubMed:29224781}; CC -!- ACTIVITY REGULATION: Catalytically inactive when the propeptide is CC intact and associated with the mature enzyme (By similarity). The CC disintegrin and cysteine-rich regions modulate access of substrates to CC exerts an inhibitory effect on the cleavage of ADAM10 substrates CC (PubMed:29224781). {ECO:0000250|UniProtKB:Q10741, CC ECO:0000269|PubMed:29224781}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=22 uM for substrate (in complex with TSPAN15) CC {ECO:0000269|PubMed:37516108}; CC -!- SUBUNIT: Forms a ternary EFNA5-EPHA3-ADAM10 complex mediating EFNA5 CC extracellular domain shedding by ADAM10 which regulates the EFNA5-EPHA3 CC complex internalization and function, the cleavage occurs in trans, CC with ADAM10 and its substrate being on the membranes of opposing cells CC (PubMed:16239146). Interacts with the clathrin adapter AP2 complex CC subunits AP2A1, AP2A2, AP2B1, and AP2M1; this interaction facilitates CC ADAM10 endocytosis from the plasma membrane during long-term CC potentiation in hippocampal neurons (PubMed:23676497). Forms a ternary CC complex composed of ADAM10, EPHA4 and CADH1; within the complex, ADAM10 CC cleaves CADH1 which disrupts adherens junctions (By similarity). CC Interacts with EPHA2 (By similarity). Interacts with NGF in a divalent CC cation-dependent manner (PubMed:20164177). Interacts with TSPAN14; the CC interaction promotes ADAM10 maturation and cell surface expression CC (PubMed:26686862, PubMed:26668317). Interacts with TSPAN5, TSPAN10, CC TSPAN14, TSPAN15, TSPAN17 and TSPAN33; these interactions regulate CC ADAM10 substrate specificity, endocytosis and turnover CC (PubMed:26668317, PubMed:26686862, PubMed:34739841, PubMed:37516108). CC Interacts (via extracellular domain) with TSPAN33 (via extracellular CC domain) and (via cytoplasmic domain) with AFDN; interaction with CC TSPAN33 allows the docking of ADAM10 to zonula adherens through a CC PDZ11-dependent interaction between TSPAN33 and PLEKHA7 while CC interaction with AFDN locks ADAM10 at zonula adherens CC (PubMed:30463011). Interacts with DLG1; this interaction recruits CC ADAM10 to the cell membrane during long-term depression in hippocampal CC neurons (PubMed:23676497). Interacts (via extracellular domain) with CC BACE1 (via extracellular domain) (By similarity). Interacts with CC FAM171A1 (PubMed:30312582). {ECO:0000250|UniProtKB:O35598, CC ECO:0000269|PubMed:16239146, ECO:0000269|PubMed:20164177, CC ECO:0000269|PubMed:23676497, ECO:0000269|PubMed:26668317, CC ECO:0000269|PubMed:26686862, ECO:0000269|PubMed:30312582, CC ECO:0000269|PubMed:30463011, ECO:0000269|PubMed:34739841, CC ECO:0000269|PubMed:37516108}. CC -!- SUBUNIT: (Microbial infection) Interacts with S.aureus hly; this CC interaction is necessary for toxin pore formation, disruption of focal CC adhesions and S.aureus hly-mediated cytotoxicity. CC {ECO:0000269|PubMed:20624979, ECO:0000269|PubMed:30463011}. CC -!- INTERACTION: CC O14672; P00519: ABL1; NbExp=2; IntAct=EBI-1536151, EBI-375543; CC O14672; P05067: APP; NbExp=7; IntAct=EBI-1536151, EBI-77613; CC O14672; P56817: BACE1; NbExp=3; IntAct=EBI-1536151, EBI-2433139; CC O14672; P60033: CD81; NbExp=9; IntAct=EBI-1536151, EBI-712921; CC O14672; P21926: CD9; NbExp=17; IntAct=EBI-1536151, EBI-4280101; CC O14672; P06241: FYN; NbExp=2; IntAct=EBI-1536151, EBI-515315; CC O14672; Q13588: GRAP; NbExp=2; IntAct=EBI-1536151, EBI-2847510; CC O14672; O75791: GRAP2; NbExp=3; IntAct=EBI-1536151, EBI-740418; CC O14672; P62993: GRB2; NbExp=5; IntAct=EBI-1536151, EBI-401755; CC O14672; P08631: HCK; NbExp=2; IntAct=EBI-1536151, EBI-346340; CC O14672; P06239: LCK; NbExp=3; IntAct=EBI-1536151, EBI-1348; CC O14672; Q9BY11: PACSIN1; NbExp=2; IntAct=EBI-1536151, EBI-721769; CC O14672; Q9UNF0: PACSIN2; NbExp=2; IntAct=EBI-1536151, EBI-742503; CC O14672; Q9UKS6: PACSIN3; NbExp=3; IntAct=EBI-1536151, EBI-77926; CC O14672; Q99961: SH3GL1; NbExp=2; IntAct=EBI-1536151, EBI-697911; CC O14672; Q96RF0: SNX18; NbExp=2; IntAct=EBI-1536151, EBI-298169; CC O14672; P12931: SRC; NbExp=3; IntAct=EBI-1536151, EBI-621482; CC O14672; O95859: TSPAN12; NbExp=2; IntAct=EBI-1536151, EBI-2466403; CC O14672; Q8NG11: TSPAN14; NbExp=9; IntAct=EBI-1536151, EBI-6308913; CC O14672; O95858: TSPAN15; NbExp=9; IntAct=EBI-1536151, EBI-7361096; CC O14672; Q86UF1: TSPAN33; NbExp=3; IntAct=EBI-1536151, EBI-12045841; CC O14672; P62079: TSPAN5; NbExp=11; IntAct=EBI-1536151, EBI-20977525; CC O14672; P07947: YES1; NbExp=2; IntAct=EBI-1536151, EBI-515331; CC PRO_0000029067; P60033: CD81; NbExp=2; IntAct=EBI-21222747, EBI-712921; CC PRO_0000029067; O95859: TSPAN12; NbExp=2; IntAct=EBI-21222747, EBI-2466403; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:20624979, CC ECO:0000269|PubMed:23676497, ECO:0000269|PubMed:24990881, CC ECO:0000269|PubMed:26686862, ECO:0000269|PubMed:29430990, CC ECO:0000269|PubMed:30463011}; Single-pass type I membrane protein CC {ECO:0000305}. Golgi apparatus membrane {ECO:0000269|PubMed:12475894}; CC Single-pass type I membrane protein {ECO:0000305}. Cytoplasmic vesicle, CC clathrin-coated vesicle {ECO:0000269|PubMed:12475894}. Cell projection, CC axon {ECO:0000250|UniProtKB:O35598}. Cell projection, dendrite CC {ECO:0000250|UniProtKB:O35598}. Cell junction, adherens junction CC {ECO:0000269|PubMed:30463011}. Cytoplasm {ECO:0000269|PubMed:30463011}. CC Note=Is localized in the plasma membrane but is also expressed in the CC Golgi apparatus and in clathrin-coated vesicles derived likely from the CC Golgi (PubMed:12475894). During long term depression, it is recruited CC to the cell membrane by DLG1 (PubMed:23676497). The immature form is CC mainly located near cytoplasmic fibrillar structures, while the mature CC form is predominantly located at zonula adherens and the cell membrane CC (PubMed:30463011). The localization and clustering of mature ADAM10 to CC zonula adherens is regulated by AFDN, TSPAN33, PLEKHA7 and PDZD11 CC (PubMed:30463011). {ECO:0000269|PubMed:12475894, CC ECO:0000269|PubMed:23676497, ECO:0000269|PubMed:30463011}. 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 -!- TISSUE SPECIFICITY: Expressed in the brain (at protein level) CC (PubMed:23676497). Expressed in spleen, lymph node, thymus, peripheral CC blood leukocyte, bone marrow, cartilage, chondrocytes and fetal liver CC (PubMed:11511685, PubMed:9016778). {ECO:0000269|PubMed:11511685, CC ECO:0000269|PubMed:23676497, ECO:0000269|PubMed:9016778}. CC -!- INDUCTION: In osteoarthritis affected-cartilage. CC -!- DOMAIN: The propeptide keeps the metalloprotease in a latent form via a CC cysteine switch mechanism. This mechanism may be mediated by a highly CC conserved cysteine (Cys-173) in the propeptide, which interacts and CC neutralizes the zinc-coordinating HEXGHXXGXXHD catalytic core of the CC metalloprotease domain. The dissociation of the cysteine from the zinc CC ion upon the activation-peptide release activates the enzyme. CC {ECO:0000250|UniProtKB:P03956}. CC -!- DOMAIN: The Cys-rich region C-terminal to the disintegrin domain CC functions as a substrate-recognition module, it recognizes the EFNA5- CC EPHA3 complex but not the individual proteins (By similarity). Both CC Cys-rich and stalk region are necessary for interaction with TSPAN5, CC TSPAN10, TSPAN14, TSPAN17, TSPAN33 (PubMed:26668317). Stalk region is CC sufficient for interaction with TSPAN15 (By similarity). CC {ECO:0000250|UniProtKB:O35598, ECO:0000250|UniProtKB:Q10741, CC ECO:0000269|PubMed:26668317}. CC -!- PTM: The precursor is cleaved by furin and PCSK7. CC {ECO:0000250|UniProtKB:Q10741}. CC -!- DISEASE: Reticulate acropigmentation of Kitamura (RAK) [MIM:615537]: A CC rare cutaneous pigmentation disorder characterized by reticulate, CC slightly depressed, sharply demarcated brown macules without CC hypopigmentation, affecting the dorsa of the hands and feet and CC appearing in the first or second decade of life. The macules gradually CC darken and extend to the proximal regions of the extremities. The CC manifestations tend to progress until middle age, after which CC progression of the eruptions stops. The pigmentary augmentation is CC found on the flexor aspects of the wrists, neck, patella and olecranon. CC Other features include breaks in the epidermal ridges on the palms and CC fingers, palmoplantar pits, occasionally plantar keratoderma, and CC partial alopecia. {ECO:0000269|PubMed:23666529}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- DISEASE: Alzheimer disease 18 (AD18) [MIM:615590]: A late-onset form of CC Alzheimer disease. Alzheimer disease is a neurodegenerative disorder CC characterized by progressive dementia, loss of cognitive abilities, and CC deposition of fibrillar amyloid proteins as intraneuronal CC neurofibrillary tangles, extracellular amyloid plaques and vascular CC amyloid deposits. The major constituents of these plaques are CC neurotoxic amyloid-beta protein 40 and amyloid-beta protein 42, that CC are produced by the proteolysis of the transmembrane APP protein. The CC cytotoxic C-terminal fragments (CTFs) and the caspase-cleaved products, CC such as C31, are also implicated in neuronal death. CC {ECO:0000269|PubMed:19608551, ECO:0000269|PubMed:24055016}. CC Note=Disease susceptibility is associated with variants affecting the CC gene represented in this entry. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/44397/ADAM10"; 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 PDB; 6BDZ; X-ray; 3.10 A; A=220-654. DR PDB; 6BE6; X-ray; 2.80 A; A/B/C/D=214-654. DR PDB; 8ESV; EM; 3.30 A; A=214-748. DR PDBsum; 6BDZ; -. DR PDBsum; 6BE6; -. DR PDBsum; 8ESV; -. DR AlphaFoldDB; O14672; -. DR EMDB; EMD-28580; -. DR SMR; O14672; -. DR BioGRID; 106616; 119. DR DIP; DIP-39889N; -. DR IntAct; O14672; 105. DR MINT; O14672; -. DR STRING; 9606.ENSP00000260408; -. DR BindingDB; O14672; -. DR ChEMBL; CHEMBL5028; -. DR DrugBank; DB04991; XL784. DR GuidetoPHARMACOLOGY; 1658; -. DR MEROPS; M12.210; -. DR TCDB; 8.A.77.1.4; the sheddase (sheddase) family. DR GlyConnect; 1178; 5 N-Linked glycans (2 sites). DR GlyCosmos; O14672; 5 sites, 6 glycans. DR GlyGen; O14672; 13 sites, 6 N-linked glycans (2 sites), 3 O-linked glycans (7 sites). DR iPTMnet; O14672; -. DR PhosphoSitePlus; O14672; -. DR SwissPalm; O14672; -. DR BioMuta; ADAM10; -. DR EPD; O14672; -. DR jPOST; O14672; -. DR MassIVE; O14672; -. DR MaxQB; O14672; -. DR PaxDb; 9606-ENSP00000260408; -. DR PeptideAtlas; O14672; -. DR ProteomicsDB; 48162; -. [O14672-1] DR ProteomicsDB; 5144; -. DR Pumba; O14672; -. DR ABCD; O14672; 29 sequenced antibodies. DR Antibodypedia; 3441; 643 antibodies from 42 providers. DR DNASU; 102; -. DR Ensembl; ENST00000260408.8; ENSP00000260408.3; ENSG00000137845.15. [O14672-1] DR GeneID; 102; -. DR KEGG; hsa:102; -. DR MANE-Select; ENST00000260408.8; ENSP00000260408.3; NM_001110.4; NP_001101.1. DR UCSC; uc002afd.3; human. [O14672-1] DR AGR; HGNC:188; -. DR CTD; 102; -. DR DisGeNET; 102; -. DR GeneCards; ADAM10; -. DR HGNC; HGNC:188; ADAM10. DR HPA; ENSG00000137845; Low tissue specificity. DR MalaCards; ADAM10; -. DR MIM; 602192; gene. DR MIM; 615537; phenotype. DR MIM; 615590; phenotype. DR neXtProt; NX_O14672; -. DR NIAGADS; ENSG00000137845; -. DR OpenTargets; ENSG00000137845; -. DR Orphanet; 178307; Reticulate acropigmentation of Kitamura. DR PharmGKB; PA24505; -. DR VEuPathDB; HostDB:ENSG00000137845; -. DR eggNOG; KOG3658; Eukaryota. DR GeneTree; ENSGT00940000160579; -. DR HOGENOM; CLU_004602_0_0_1; -. DR InParanoid; O14672; -. DR OMA; CRKVDAD; -. DR OrthoDB; 5395001at2759; -. DR PhylomeDB; O14672; -. DR TreeFam; TF352021; -. DR BioCyc; MetaCyc:ENSG00000137845-MONOMER; -. DR BRENDA; 3.4.24.81; 2681. DR PathwayCommons; O14672; -. 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-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-381426; Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs). DR Reactome; R-HSA-3928665; EPH-ephrin mediated repulsion of cells. DR Reactome; R-HSA-6798695; Neutrophil degranulation. DR Reactome; R-HSA-8957275; Post-translational protein phosphorylation. DR Reactome; R-HSA-9013507; NOTCH3 Activation and Transmission of Signal to the Nucleus. DR Reactome; R-HSA-9013700; NOTCH4 Activation and Transmission of Signal to the Nucleus. DR Reactome; R-HSA-977225; Amyloid fiber formation. DR SignaLink; O14672; -. DR SIGNOR; O14672; -. DR BioGRID-ORCS; 102; 28 hits in 1161 CRISPR screens. DR ChiTaRS; ADAM10; human. DR GeneWiki; ADAM10; -. DR GenomeRNAi; 102; -. DR Pharos; O14672; Tchem. DR PRO; PR:O14672; -. DR Proteomes; UP000005640; Chromosome 15. DR RNAct; O14672; Protein. DR Bgee; ENSG00000137845; Expressed in stromal cell of endometrium and 220 other cell types or tissues. DR ExpressionAtlas; O14672; baseline and differential. DR GO; GO:0005912; C:adherens junction; IEA:UniProtKB-SubCell. DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0030136; C:clathrin-coated vesicle; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell. DR GO; GO:0005788; C:endoplasmic reticulum lumen; TAS:Reactome. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005925; C:focal adhesion; HDA:UniProtKB. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0005794; C:Golgi apparatus; IDA:UniProtKB. DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005798; C:Golgi-associated vesicle; IDA:UniProtKB. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0016020; C:membrane; HDA: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; IDA:HPA. DR GO; GO:0046930; C:pore complex; IMP:UniProtKB. DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl. DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome. DR GO; GO:0097060; C:synaptic membrane; IDA:UniProtKB. DR GO; GO:0070821; C:tertiary granule membrane; TAS:Reactome. DR GO; GO:0097197; C:tetraspanin-enriched microdomain; IDA:UniProtKB. DR GO; GO:0004175; F:endopeptidase activity; IMP:UniProtKB. DR GO; GO:0005178; F:integrin binding; NAS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0070573; F:metallodipeptidase activity; IEA:Ensembl. DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:BHF-UCL. DR GO; GO:1902945; F:metalloendopeptidase activity involved in amyloid precursor protein catabolic process; IMP:UniProtKB. DR GO; GO:0008237; F:metallopeptidase activity; IDA:UniProtKB. DR GO; GO:0060090; F:molecular adaptor activity; EXP:DisProt. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; ISS:UniProtKB. DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW. DR GO; GO:0005102; F:signaling receptor binding; NAS:UniProtKB. DR GO; GO:0034332; P:adherens junction organization; IEA:Ensembl. DR GO; GO:0042987; P:amyloid precursor protein catabolic process; IMP:UniProtKB. DR GO; GO:0007267; P:cell-cell signaling; NAS:UniProtKB. DR GO; GO:0090102; P:cochlea development; IEA:Ensembl. DR GO; GO:0051089; P:constitutive protein ectodomain proteolysis; IDA:UniProtKB. DR GO; GO:0038004; P:epidermal growth factor receptor ligand maturation; IEA:Ensembl. DR GO; GO:0022617; P:extracellular matrix disassembly; 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:0010629; P:negative regulation of gene expression; IMP:ARUK-UCL. DR GO; GO:0007219; P:Notch signaling pathway; ISS:UniProtKB. DR GO; GO:0046931; P:pore complex assembly; IMP:UniProtKB. 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 population proliferation; IMP:BHF-UCL. DR GO; GO:0010820; P:positive regulation of T cell chemotaxis; IMP:BHF-UCL. DR GO; GO:0099173; P:postsynapse organization; IEA:Ensembl. DR GO; GO:0140249; P:protein catabolic process at postsynapse; IEA:Ensembl. DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB. DR GO; GO:0016485; P:protein processing; ISS:ARUK-UCL. DR GO; GO:0098696; P:regulation of neurotransmitter receptor localization to postsynaptic specialization membrane; IEA:Ensembl. DR GO; GO:0008593; P:regulation of Notch signaling pathway; IEA:Ensembl. DR GO; GO:0099175; P:regulation of postsynapse organization; IEA:Ensembl. DR GO; GO:1901342; P:regulation of vasculature development; IEA:Ensembl. DR GO; GO:0034612; P:response to tumor necrosis factor; IDA:BHF-UCL. DR GO; GO:1901998; P:toxin transport; IMP:UniProtKB. DR CDD; cd04270; ZnMc_TACE_like; 1. DR DisProt; DP02318; -. DR Gene3D; 3.40.390.10; Collagenase (Catalytic Domain); 1. DR Gene3D; 4.10.70.10; Disintegrin domain; 1. DR InterPro; IPR034025; ADAM10_ADAM17. DR InterPro; IPR049038; ADAM10_Cys-rich. DR InterPro; IPR001762; Disintegrin_dom. DR InterPro; IPR036436; Disintegrin_dom_sf. DR InterPro; IPR024079; MetalloPept_cat_dom_sf. DR InterPro; IPR001590; Peptidase_M12B. DR PANTHER; PTHR45702; ADAM10/ADAM17 METALLOPEPTIDASE FAMILY MEMBER; 1. DR PANTHER; PTHR45702:SF4; DISINTEGRIN AND METALLOPROTEINASE DOMAIN-CONTAINING PROTEIN 10; 1. DR Pfam; PF21299; ADAM10_Cys-rich; 1. DR Pfam; PF00200; Disintegrin; 1. DR Pfam; PF13574; Reprolysin_2; 1. DR SMART; SM00050; DISIN; 1. DR SUPFAM; SSF57552; Blood coagulation inhibitor (disintegrin); 1. DR SUPFAM; SSF55486; Metalloproteases ('zincins'), catalytic domain; 1. DR PROSITE; PS50215; ADAM_MEPRO; 1. DR PROSITE; PS50214; DISINTEGRIN_2; 1. DR PROSITE; PS00142; ZINC_PROTEASE; 1. DR Genevisible; O14672; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Alzheimer disease; Amyloidosis; KW Cell junction; Cell membrane; Cell projection; KW Cleavage on pair of basic residues; Cytoplasm; Cytoplasmic vesicle; KW Direct protein sequencing; Disease variant; Disulfide bond; Glycoprotein; KW Golgi apparatus; Hydrolase; Membrane; Metal-binding; Metalloprotease; KW Neurodegeneration; Notch signaling pathway; Phosphoprotein; Protease; KW Reference proteome; SH3-binding; Signal; Transmembrane; KW Transmembrane helix; Zinc; Zymogen. FT SIGNAL 1..19 FT /evidence="ECO:0000255" FT PROPEP 20..213 FT /evidence="ECO:0000250|UniProtKB:Q10741" FT /id="PRO_0000029066" FT CHAIN 214..748 FT /note="Disintegrin and metalloproteinase domain-containing FT protein 10" FT /id="PRO_0000029067" FT TOPO_DOM 20..672 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 673..693 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 694..748 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 220..456 FT /note="Peptidase M12B" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00276" FT DOMAIN 457..551 FT /note="Disintegrin" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068" FT REGION 704..748 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 734..748 FT /note="Interaction with AP2A1, AP2A2 and AP2M1" FT /evidence="ECO:0000250|UniProtKB:O35598" FT MOTIF 171..178 FT /note="Cysteine switch" FT /evidence="ECO:0000250" FT MOTIF 708..715 FT /note="SH3-binding" FT /evidence="ECO:0000255" FT MOTIF 722..728 FT /note="SH3-binding" FT /evidence="ECO:0000255" FT COMPBIAS 706..722 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT ACT_SITE 384 FT /evidence="ECO:0000269|PubMed:29224781, FT ECO:0000269|PubMed:29430990" FT BINDING 173 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /note="in inhibited form" FT /evidence="ECO:0000250|UniProtKB:P03956" FT BINDING 383 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:24055016, FT ECO:0000269|PubMed:29224781, ECO:0000269|PubMed:37516108, FT ECO:0007744|PDB:6BDZ, ECO:0007744|PDB:6BE6, FT ECO:0007744|PDB:8ESV" FT BINDING 387 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:29224781, FT ECO:0000269|PubMed:37516108, ECO:0007744|PDB:6BE6, FT ECO:0007744|PDB:8ESV" FT BINDING 393 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_note="catalytic" FT /evidence="ECO:0000269|PubMed:24055016, FT ECO:0000269|PubMed:29224781, ECO:0000269|PubMed:37516108, FT ECO:0007744|PDB:6BDZ, ECO:0007744|PDB:6BE6, FT ECO:0007744|PDB:8ESV" FT SITE 213..214 FT /note="Cleavage; by furin and PCSK7" FT /evidence="ECO:0000250|UniProtKB:Q10741" FT MOD_RES 719 FT /note="Phosphothreonine; by FAM20C" FT /evidence="ECO:0000269|PubMed:26091039, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT CARBOHYD 267 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 278 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:16263699, FT ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:19349973, FT ECO:0000269|PubMed:29224781, ECO:0007744|PDB:6BDZ, FT ECO:0007744|PDB:6BE6" FT CARBOHYD 439 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 551 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 222..313 FT /evidence="ECO:0000269|PubMed:29224781, FT ECO:0000269|PubMed:37516108, ECO:0007744|PDB:6BDZ, FT ECO:0007744|PDB:6BE6, ECO:0007744|PDB:8ESV" FT DISULFID 344..451 FT /evidence="ECO:0000269|PubMed:29224781, FT ECO:0000269|PubMed:37516108, ECO:0007744|PDB:6BDZ, FT ECO:0007744|PDB:6BE6, ECO:0007744|PDB:8ESV" FT DISULFID 399..435 FT /evidence="ECO:0000269|PubMed:29224781, FT ECO:0000269|PubMed:37516108, ECO:0007744|PDB:6BDZ, FT ECO:0007744|PDB:6BE6, ECO:0007744|PDB:8ESV" FT DISULFID 460..495 FT /evidence="ECO:0000269|PubMed:29224781, FT ECO:0000269|PubMed:37516108, ECO:0007744|PDB:6BDZ, FT ECO:0007744|PDB:6BE6, ECO:0007744|PDB:8ESV" FT DISULFID 471..484 FT /evidence="ECO:0000269|PubMed:29224781, FT ECO:0000269|PubMed:37516108, ECO:0007744|PDB:6BDZ, FT ECO:0007744|PDB:6BE6, ECO:0007744|PDB:8ESV" FT DISULFID 473..479 FT /evidence="ECO:0000269|PubMed:29224781, FT ECO:0000269|PubMed:37516108, ECO:0007744|PDB:6BDZ, FT ECO:0007744|PDB:6BE6, ECO:0007744|PDB:8ESV" FT DISULFID 483..515 FT /evidence="ECO:0000269|PubMed:29224781, FT ECO:0000269|PubMed:37516108, ECO:0007744|PDB:6BDZ, FT ECO:0007744|PDB:6BE6, ECO:0007744|PDB:8ESV" FT DISULFID 503..511 FT /evidence="ECO:0000269|PubMed:29224781, FT ECO:0000269|PubMed:37516108, ECO:0007744|PDB:6BDZ, FT ECO:0007744|PDB:6BE6, ECO:0007744|PDB:8ESV" FT DISULFID 510..536 FT /evidence="ECO:0000269|PubMed:29224781, FT ECO:0000269|PubMed:37516108, ECO:0007744|PDB:6BDZ, FT ECO:0007744|PDB:6BE6, ECO:0007744|PDB:8ESV" FT DISULFID 524..543 FT /evidence="ECO:0000269|PubMed:29224781, FT ECO:0000269|PubMed:37516108, ECO:0007744|PDB:6BDZ, FT ECO:0007744|PDB:6BE6, ECO:0007744|PDB:8ESV" FT DISULFID 530..562 FT /evidence="ECO:0000269|PubMed:29224781, FT ECO:0000269|PubMed:37516108, ECO:0007744|PDB:6BDZ, FT ECO:0007744|PDB:6BE6, ECO:0007744|PDB:8ESV" FT DISULFID 555..567 FT /evidence="ECO:0000269|PubMed:29224781, FT ECO:0000269|PubMed:37516108, ECO:0007744|PDB:6BDZ, FT ECO:0007744|PDB:6BE6, ECO:0007744|PDB:8ESV" FT DISULFID 572..598 FT /evidence="ECO:0000269|PubMed:29224781, FT ECO:0000269|PubMed:37516108, ECO:0007744|PDB:6BDZ, FT ECO:0007744|PDB:6BE6, ECO:0007744|PDB:8ESV" FT DISULFID 580..607 FT /evidence="ECO:0000269|PubMed:29224781, FT ECO:0000269|PubMed:37516108, ECO:0007744|PDB:6BDZ, FT ECO:0007744|PDB:6BE6, ECO:0007744|PDB:8ESV" FT DISULFID 582..597 FT /evidence="ECO:0000269|PubMed:29224781, FT ECO:0000269|PubMed:37516108, ECO:0007744|PDB:6BDZ, FT ECO:0007744|PDB:6BE6, ECO:0007744|PDB:8ESV" FT DISULFID 594..639 FT /evidence="ECO:0000269|PubMed:29224781, FT ECO:0000269|PubMed:37516108, ECO:0007744|PDB:6BDZ, FT ECO:0007744|PDB:6BE6, ECO:0007744|PDB:8ESV" FT DISULFID 632..645 FT /evidence="ECO:0000269|PubMed:29224781, FT ECO:0007744|PDB:6BDZ, ECO:0007744|PDB:6BE6" FT VAR_SEQ 19..319 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_056401" FT VARIANT 139 FT /note="P -> S (in RAK; dbSNP:rs483352912)" FT /evidence="ECO:0000269|PubMed:23666529" FT /id="VAR_070907" FT VARIANT 170 FT /note="Q -> H (in AD18; associated with disease FT susceptibility; significantly attenuates alpha-secretase FT activity of the enzyme; shifts APP processing toward FT beta-secretase-mediated cleavage resulting in enhanced FT amyloid-beta plaque load and reactive gliosis; FT dbSNP:rs61751103)" FT /evidence="ECO:0000269|PubMed:19608551, FT ECO:0000269|PubMed:24055016" FT /id="VAR_070908" FT VARIANT 176 FT /note="H -> Y (in a cutaneous metastatic melanoma sample; FT somatic mutation; dbSNP:rs267604273)" FT /evidence="ECO:0000269|PubMed:21618342" FT /id="VAR_066309" FT VARIANT 181 FT /note="R -> G (in AD18; associated with disease FT susceptibility; significantly attenuates alpha-secretase FT activity of the enzyme; shifts APP processing toward FT beta-secretase-mediated cleavage resulting in enhanced FT amyloid-beta plaque load and reactive gliosis; FT dbSNP:rs145518263)" FT /evidence="ECO:0000269|PubMed:19608551, FT ECO:0000269|PubMed:24055016" FT /id="VAR_070909" FT VARIANT 524 FT /note="C -> Y (in RAK; dbSNP:rs483352916)" FT /evidence="ECO:0000269|PubMed:23666529" FT /id="VAR_070910" FT MUTAGEN 384 FT /note="E->A: Loss of proteolytic activity. Abrogates APP FT cleavage. Reduces Notch signaling." FT /evidence="ECO:0000269|PubMed:29224781, FT ECO:0000269|PubMed:29430990" FT MUTAGEN 638..646 FT /note="YCDVFMRCR->ACDVFMRCA: Strongly reduces interaction FT and ADAM10 maturation." FT /evidence="ECO:0000269|PubMed:37516108" FT MUTAGEN 638..646 FT /note="YCDVFMRCR->ECDVFMRCE: Strongly reduces interaction FT and prevents ADAM10 maturation." FT /evidence="ECO:0000269|PubMed:37516108" FT MUTAGEN 653..656 FT /note="PLAR->AAAA: Strongly reduces interaction and FT prevents ADAM10 maturation." FT /evidence="ECO:0000269|PubMed:37516108" FT CONFLICT 162 FT /note="N -> SERLKLRLRKLMSLELWTSCCLPCALLLHSWKKAVNSHCLYFKDFWG FT FSEIY (in Ref. 2; CAA88463)" FT /evidence="ECO:0000305" FT CONFLICT 212 FT /note="K -> R (in Ref. 2; CAA88463)" FT /evidence="ECO:0000305" FT CONFLICT 296 FT /note="G -> S (in Ref. 2; CAA88463)" FT /evidence="ECO:0000305" FT STRAND 219..228 FT /evidence="ECO:0007829|PDB:6BE6" FT HELIX 230..236 FT /evidence="ECO:0007829|PDB:6BE6" FT HELIX 239..258 FT /evidence="ECO:0007829|PDB:6BE6" FT STRAND 269..277 FT /evidence="ECO:0007829|PDB:6BE6" FT HELIX 280..284 FT /evidence="ECO:0007829|PDB:6BE6" FT HELIX 289..291 FT /evidence="ECO:0007829|PDB:8ESV" FT HELIX 297..305 FT /evidence="ECO:0007829|PDB:6BE6" FT STRAND 313..322 FT /evidence="ECO:0007829|PDB:6BE6" FT HELIX 324..326 FT /evidence="ECO:0007829|PDB:6BE6" FT STRAND 329..331 FT /evidence="ECO:0007829|PDB:6BE6" FT STRAND 336..338 FT /evidence="ECO:0007829|PDB:6BE6" FT STRAND 348..350 FT /evidence="ECO:0007829|PDB:6BE6" FT STRAND 359..367 FT /evidence="ECO:0007829|PDB:6BE6" FT HELIX 374..388 FT /evidence="ECO:0007829|PDB:6BE6" FT TURN 397..399 FT /evidence="ECO:0007829|PDB:6BE6" FT HELIX 401..403 FT /evidence="ECO:0007829|PDB:6BE6" FT HELIX 407..411 FT /evidence="ECO:0007829|PDB:6BE6" FT HELIX 428..430 FT /evidence="ECO:0007829|PDB:6BE6" FT HELIX 434..447 FT /evidence="ECO:0007829|PDB:6BE6" FT HELIX 448..450 FT /evidence="ECO:0007829|PDB:6BE6" FT STRAND 462..464 FT /evidence="ECO:0007829|PDB:6BE6" FT TURN 476..478 FT /evidence="ECO:0007829|PDB:6BE6" FT STRAND 482..484 FT /evidence="ECO:0007829|PDB:8ESV" FT TURN 491..495 FT /evidence="ECO:0007829|PDB:6BE6" FT TURN 505..507 FT /evidence="ECO:0007829|PDB:6BE6" FT STRAND 509..511 FT /evidence="ECO:0007829|PDB:6BE6" FT STRAND 515..517 FT /evidence="ECO:0007829|PDB:8ESV" FT STRAND 523..525 FT /evidence="ECO:0007829|PDB:6BE6" FT STRAND 529..531 FT /evidence="ECO:0007829|PDB:6BE6" FT STRAND 553..555 FT /evidence="ECO:0007829|PDB:6BDZ" FT TURN 556..559 FT /evidence="ECO:0007829|PDB:6BE6" FT STRAND 560..563 FT /evidence="ECO:0007829|PDB:6BE6" FT STRAND 566..569 FT /evidence="ECO:0007829|PDB:6BE6" FT HELIX 571..575 FT /evidence="ECO:0007829|PDB:6BE6" FT STRAND 577..580 FT /evidence="ECO:0007829|PDB:6BE6" FT HELIX 591..593 FT /evidence="ECO:0007829|PDB:8ESV" FT STRAND 597..600 FT /evidence="ECO:0007829|PDB:6BE6" FT HELIX 604..606 FT /evidence="ECO:0007829|PDB:6BE6" FT HELIX 614..617 FT /evidence="ECO:0007829|PDB:6BE6" FT STRAND 630..632 FT /evidence="ECO:0007829|PDB:6BDZ" FT TURN 633..636 FT /evidence="ECO:0007829|PDB:6BE6" FT STRAND 637..639 FT /evidence="ECO:0007829|PDB:6BE6" FT STRAND 645..647 FT /evidence="ECO:0007829|PDB:6BE6" FT HELIX 653..662 FT /evidence="ECO:0007829|PDB:8ESV" FT HELIX 665..669 FT /evidence="ECO:0007829|PDB:8ESV" 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 //