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ADA10_HUMAN
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   03-AUG-2022, entry version 214.
DE   RecName: Full=Disintegrin and metalloproteinase domain-containing protein 10;
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; 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   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   [34]
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   [35]
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   [36]
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).
RN   [37] {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).
CC   -!- FUNCTION: Cleaves the membrane-bound precursor of TNF-alpha at '76-
CC       Ala-|-Val-77' to its mature soluble form. Responsible for the
CC       proteolytical release of soluble JAM3 from endothelial cells surface
CC       (PubMed:20592283). Responsible for the proteolytic release of several
CC       other cell-surface proteins, including heparin-binding epidermal
CC       growth-like factor, ephrin-A2, CD44, CDH2 and for constitutive and
CC       regulated alpha-secretase cleavage of amyloid precursor protein (APP)
CC       (PubMed:26686862, PubMed:11786905, PubMed:29224781). 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). {ECO:0000250|UniProtKB:O35598,
CC       ECO:0000269|PubMed:11477090, ECO:0000269|PubMed:11786905,
CC       ECO:0000269|PubMed:12475894, ECO:0000269|PubMed:16239146,
CC       ECO:0000269|PubMed:17557115, ECO:0000269|PubMed:19114711,
CC       ECO:0000269|PubMed:20592283, ECO:0000269|PubMed:21288900,
CC       ECO:0000269|PubMed:24990881, ECO:0000269|PubMed:26686862,
CC       ECO:0000269|PubMed:26876177, ECO:0000269|PubMed:29224781}.
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: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   -!- 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). Interacts (via
CC       extracellular domain) with TSPAN33 (via extracellular domain) and (via
CC       cytoplasmic domain) with AFDN; interaction with TSPAN33 allows the
CC       docking of ADAM10 to zonula adherens through a PDZ11-dependent
CC       interaction between TSPAN33 and PLEKHA7 while interaction with AFDN
CC       locks ADAM10 at zonula adherens (PubMed:30463011). 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       TSPAN15, TSPAN17 and TSPAN33; these interactions regulate ADAM10
CC       substrate specificity (PubMed:26686862). Interacts with DLG1; this
CC       interaction recruits ADAM10 to the cell membrane during long-term
CC       depression in hippocampal neurons (PubMed:23676497). Interacts (via
CC       extracellular domain) with BACE1 (via extracellular domain) (By
CC       similarity). Interacts with FAM171A1 (PubMed:30312582).
CC       {ECO:0000250|UniProtKB:O35598, ECO:0000269|PubMed:16239146,
CC       ECO:0000269|PubMed:20164177, ECO:0000269|PubMed:23676497,
CC       ECO:0000269|PubMed:26668317, ECO:0000269|PubMed:26686862,
CC       ECO:0000269|PubMed:30312582, ECO:0000269|PubMed:30463011}.
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="http://atlasgeneticsoncology.org/Genes/ADAM10ID44397ch15q21.html";
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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   PDBsum; 6BDZ; -.
DR   PDBsum; 6BE6; -.
DR   AlphaFoldDB; O14672; -.
DR   SMR; O14672; -.
DR   BioGRID; 106616; 111.
DR   DIP; DIP-39889N; -.
DR   IntAct; O14672; 102.
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   GlyGen; O14672; 7 sites, 6 N-linked glycans (2 sites), 1 O-linked glycan (1 site).
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; O14672; -.
DR   PeptideAtlas; O14672; -.
DR   PRIDE; O14672; -.
DR   ProteomicsDB; 48162; -. [O14672-1]
DR   ProteomicsDB; 5144; -.
DR   ABCD; O14672; 29 sequenced antibodies.
DR   Antibodypedia; 3441; 581 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   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; GICERYK; -.
DR   PhylomeDB; O14672; -.
DR   TreeFam; TF352021; -.
DR   BioCyc; MetaCyc:ENSG00000137845-MON; -.
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; 27 hits in 1083 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 218 other 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:0016021; C:integral component of membrane; NAS:UniProtKB.
DR   GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR   GO; GO:0016020; C:membrane; 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: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: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: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; -; 1.
DR   Gene3D; 4.10.70.10; -; 1.
DR   InterPro; IPR034025; ADAM10_ADAM17.
DR   InterPro; IPR027053; ADAM_10.
DR   InterPro; IPR001762; Disintegrin_dom.
DR   InterPro; IPR036436; Disintegrin_dom_sf.
DR   InterPro; IPR024079; MetalloPept_cat_dom_sf.
DR   InterPro; IPR001590; Peptidase_M12B.
DR   InterPro; IPR002870; Peptidase_M12B_N.
DR   PANTHER; PTHR45702:SF4; PTHR45702:SF4; 1.
DR   Pfam; PF00200; Disintegrin; 1.
DR   Pfam; PF01562; Pep_M12B_propep; 1.
DR   SMART; SM00050; DISIN; 1.
DR   SUPFAM; SSF57552; SSF57552; 1.
DR   PROSITE; PS50215; ADAM_MEPRO; 1.
DR   PROSITE; PS50214; DISINTEGRIN_2; 1.
DR   PROSITE; PS00142; ZINC_PROTEASE; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Alzheimer disease; Amyloidosis;
KW   Cell 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:0007744|PDB:6BDZ,
FT                   ECO:0007744|PDB:6BE6"
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:0007744|PDB:6BE6"
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:0007744|PDB:6BDZ,
FT                   ECO:0007744|PDB:6BE6"
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:0007744|PDB:6BDZ, ECO:0007744|PDB:6BE6"
FT   DISULFID        344..451
FT                   /evidence="ECO:0000269|PubMed:29224781,
FT                   ECO:0007744|PDB:6BDZ, ECO:0007744|PDB:6BE6"
FT   DISULFID        399..435
FT                   /evidence="ECO:0000269|PubMed:29224781,
FT                   ECO:0007744|PDB:6BDZ, ECO:0007744|PDB:6BE6"
FT   DISULFID        460..495
FT                   /evidence="ECO:0000269|PubMed:29224781,
FT                   ECO:0007744|PDB:6BDZ, ECO:0007744|PDB:6BE6"
FT   DISULFID        471..484
FT                   /evidence="ECO:0000269|PubMed:29224781,
FT                   ECO:0007744|PDB:6BDZ, ECO:0007744|PDB:6BE6"
FT   DISULFID        473..479
FT                   /evidence="ECO:0000269|PubMed:29224781,
FT                   ECO:0007744|PDB:6BDZ, ECO:0007744|PDB:6BE6"
FT   DISULFID        483..515
FT                   /evidence="ECO:0000269|PubMed:29224781,
FT                   ECO:0007744|PDB:6BDZ, ECO:0007744|PDB:6BE6"
FT   DISULFID        503..511
FT                   /evidence="ECO:0000269|PubMed:29224781,
FT                   ECO:0007744|PDB:6BDZ, ECO:0007744|PDB:6BE6"
FT   DISULFID        510..536
FT                   /evidence="ECO:0000269|PubMed:29224781,
FT                   ECO:0007744|PDB:6BDZ, ECO:0007744|PDB:6BE6"
FT   DISULFID        524..543
FT                   /evidence="ECO:0000269|PubMed:29224781,
FT                   ECO:0007744|PDB:6BDZ, ECO:0007744|PDB:6BE6"
FT   DISULFID        530..562
FT                   /evidence="ECO:0000269|PubMed:29224781,
FT                   ECO:0007744|PDB:6BDZ, ECO:0007744|PDB:6BE6"
FT   DISULFID        555..567
FT                   /evidence="ECO:0000269|PubMed:29224781,
FT                   ECO:0007744|PDB:6BDZ, ECO:0007744|PDB:6BE6"
FT   DISULFID        572..598
FT                   /evidence="ECO:0000269|PubMed:29224781,
FT                   ECO:0007744|PDB:6BDZ, ECO:0007744|PDB:6BE6"
FT   DISULFID        580..607
FT                   /evidence="ECO:0000269|PubMed:29224781,
FT                   ECO:0007744|PDB:6BDZ, ECO:0007744|PDB:6BE6"
FT   DISULFID        582..597
FT                   /evidence="ECO:0000269|PubMed:29224781,
FT                   ECO:0007744|PDB:6BDZ, ECO:0007744|PDB:6BE6"
FT   DISULFID        594..639
FT                   /evidence="ECO:0000269|PubMed:29224781,
FT                   ECO:0007744|PDB:6BDZ, ECO:0007744|PDB:6BE6"
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: Abrogates APP cleavage. Reduces Notch
FT                   signaling. Loss of proteolytic activity."
FT                   /evidence="ECO:0000269|PubMed:29224781,
FT                   ECO:0000269|PubMed:29430990"
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           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   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          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   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"
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
 
 
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