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 Genevisible; O14672; HS.
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.
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 beta-
FT secretase-mediated cleavage resulting in enhanced amyloid-
FT beta plaque load and reactive gliosis; 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 beta-
FT secretase-mediated cleavage resulting in enhanced amyloid-
FT beta plaque load and reactive gliosis; 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
//
