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 13-FEB-2019, entry version 193. 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; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND PROTEIN SEQUENCE OF RP 216-237. RX PubMed=9305925; DOI=10.1074/jbc.272.39.24588; RA Rosendahl M.S., Ko S.C., Long D.L., Brewer M.T., Rosenzweig B., RA Hedl E., Anderson L., Pyle S.M., Moreland J., Meyers M.A., Kohno T., RA Lyons D., Lichenstein H.S.; RT "Identification and characterization of a pro-tumor necrosis factor- RT alpha-processing enzyme from the ADAM family of zinc RT metalloproteases."; RL J. Biol. Chem. 272:24588-24593(1997). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] OF 109-748 (ISOFORM 1). RX PubMed=8694785; DOI=10.1042/bj3170045; RA Howard L., Mitchell S., Lu X., Griffiths S., Glynn P.; RT "Molecular cloning of MADM: a catalytically active mammalian RT disintegrin-metalloprotease expressed in various cell types."; RL Biochem. J. 317:45-50(1996). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16572171; DOI=10.1038/nature04601; RA Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., RA Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., RA FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., RA Abouelleil A., Arachchi H.M., Baradarani L., Birditt B., Bloom S., RA Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., RA DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., RA Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., RA Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., RA Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., RA Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., RA Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., RA Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., RA Nusbaum C.; RT "Analysis of the DNA sequence and duplication history of human RT chromosome 15."; RL Nature 440:671-675(2006). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Placenta; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP TISSUE SPECIFICITY. RX PubMed=9016778; DOI=10.1006/bbrc.1996.5957; RA McKie N., Edwards T., Dallas D.J., Houghton A., Stringer B., RA Graham R., Russell G., Croucher P.I.; RT "Expression of members of a novel membrane linked metalloproteinase RT family (ADAM) in human articular chondrocytes."; RL Biochem. Biophys. Res. Commun. 230:335-339(1997). RN [6] RP FUNCTION, 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., RA Joumaa S., Zentgraf H., Fogel M., Altevogt P.; RT "ADAM10-mediated cleavage of L1 adhesion molecule at the cell surface RT and in released membrane vesicles."; RL FASEB J. 17:292-294(2003). RN [7] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=11477090; DOI=10.1074/jbc.M105677200; RA Vincent B., Paitel E., Saftig P., Frobert Y., Hartmann D., RA De Strooper B., Grassi J., Lopez-Perez E., Checler F.; RT "The disintegrins ADAM10 and TACE contribute to the constitutive and RT phorbol ester-regulated normal cleavage of the cellular prion RT protein."; RL J. Biol. Chem. 276:37743-37746(2001). RN [8] RP TISSUE SPECIFICITY. RX PubMed=11511685; DOI=10.1177/002215540104900910; RA Chubinskaya S., Mikhail R., Deutsch A., Tindal M.H.; RT "ADAM-10 protein is present in human articular cartilage primarily in RT the membrane-bound form and is upregulated in osteoarthritis and in RT response to IL-1alpha in bovine nasal cartilage."; RL J. Histochem. Cytochem. 49:1165-1176(2001). RN [9] RP FUNCTION. RX PubMed=11786905; DOI=10.1038/nm0102-41; RA Lemjabbar H., Basbaum C.; RT "Platelet-activating factor receptor and ADAM10 mediate responses to RT Staphylococcus aureus in epithelial cells."; RL Nat. Med. 8:41-46(2002). RN [10] RP IDENTIFICATION IN A COMPLEX WITH EFNA5 AND EPHA3, FUNCTION IN RP EFNA5-EPHA3 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 RT molecular switch for ephrin cleavage in trans."; RL Cell 123:291-304(2005). RN [11] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-278. RC TISSUE=Platelet; RX PubMed=16263699; DOI=10.1074/mcp.M500324-MCP200; RA Lewandrowski U., Moebius J., Walter U., Sickmann A.; RT "Elucidation of N-glycosylation sites on human platelet proteins: a RT glycoproteomic approach."; RL Mol. Cell. Proteomics 5:226-233(2006). RN [12] RP FUNCTION IN CLEAVAGE OF FASLG. RX PubMed=17557115; DOI=10.1038/sj.cdd.4402175; RA Kirkin V., Cahuzac N., Guardiola-Serrano F., Huault S., Luckerath K., RA Friedmann E., Novac N., Wels W.S., Martoglio B., Hueber A.O., RA Zornig M.; RT "The Fas ligand intracellular domain is released by ADAM10 and SPPL2a RT cleavage in T-cells."; RL Cell Death Differ. 14:1678-1687(2007). RN [13] RP FUNCTION IN CLEAVAGE OF ITM2B. RX PubMed=19114711; DOI=10.1074/jbc.M807485200; RA Martin L., Fluhrer R., Haass C.; RT "Substrate requirements for SPPL2b-dependent regulated intramembrane RT proteolysis."; RL J. Biol. Chem. 284:5662-5670(2009). RN [14] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-278. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of RT multiple enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [15] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-278. RC TISSUE=Leukemic T-cell; RX PubMed=19349973; DOI=10.1038/nbt.1532; RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., RA Schiess R., Aebersold R., Watts J.D.; RT "Mass-spectrometric identification and relative quantification of N- RT linked cell surface glycoproteins."; RL Nat. Biotechnol. 27:378-386(2009). RN [16] RP INTERACTION WITH NGF. RX PubMed=20164177; DOI=10.1074/jbc.M110.100479; RA Wijeyewickrema L.C., Gardiner E.E., Gladigau E.L., Berndt M.C., RA Andrews R.K.; RT "Nerve growth factor inhibits metalloproteinase-disintegrins and RT blocks ectodomain shedding of platelet glycoprotein VI."; RL J. Biol. Chem. 285:11793-11799(2010). RN [17] RP FUNCTION IN CLEAVAGE OF JAM3. RX PubMed=20592283; DOI=10.4049/jimmunol.1000556; RA Rabquer B.J., Amin M.A., Teegala N., Shaheen M.K., Tsou P.S., RA Ruth J.H., Lesch C.A., Imhof B.A., Koch A.E.; RT "Junctional adhesion molecule-C is a soluble mediator of RT angiogenesis."; RL J. Immunol. 185:1777-1785(2010). RN [18] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [19] RP FUNCTION IN CLEAVAGE OF CORIN. RX PubMed=21288900; DOI=10.1074/jbc.M110.185082; RA Jiang J., Wu S., Wang W., Chen S., Peng J., Zhang X., Wu Q.; RT "Ectodomain shedding and autocleavage of the cardiac membrane protease RT corin."; RL J. Biol. Chem. 286:10066-10072(2011). RN [20] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-719, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=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 [21] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-719, AND IDENTIFICATION RP BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., RA Wang L., Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human RT liver phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [22] RP PHOSPHORYLATION AT THR-719. RX PubMed=26091039; DOI=10.1016/j.cell.2015.05.028; RA Tagliabracci V.S., Wiley S.E., Guo X., Kinch L.N., Durrant E., Wen J., RA Xiao J., Cui J., Nguyen K.B., Engel J.L., Coon J.J., Grishin N., RA Pinna L.A., Pagliarini D.J., Dixon J.E.; RT "A single kinase generates the majority of the secreted RT phosphoproteome."; RL Cell 161:1619-1632(2015). RN [23] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., RA Ayoub D., Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [24] RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, AND INTERACTION RP WITH 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 RT compartmentalization."; RL Cell. Mol. Life Sci. 73:1895-1915(2016). RN [25] 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., RA Furmston J., Rogers D.A., Rainger G.E., Tomlinson M.G.; RT "TspanC8 tetraspanins and A disintegrin and metalloprotease 10 RT (ADAM10) interact via their extracellular regions: evidence for RT distinct binding mechanisms for different TspanC8 proteins."; RL J. Biol. Chem. 291:3145-3157(2016). RN [26] RP VARIANTS AD18 HIS-170 AND GLY-181, AND CHARACTERIZATION OF VARIANTS RP AD18 HIS-170 AND GLY-181. RX PubMed=19608551; DOI=10.1093/hmg/ddp323; RA Kim M., Suh J., Romano D., Truong M.H., Mullin K., Hooli B., RA Norton D., Tesco G., Elliott K., Wagner S.L., Moir R.D., Becker K.D., RA Tanzi R.E.; RT "Potential late-onset Alzheimer's disease-associated mutations in the RT ADAM10 gene attenuate {alpha}-secretase activity."; RL Hum. Mol. Genet. 18:3987-3996(2009). RN [27] RP VARIANT TYR-176. RX PubMed=21618342; DOI=10.1002/humu.21477; RA Wei X., Moncada-Pazos A., Cal S., Soria-Valles C., Gartner J., RA Rudloff U., Lin J.C., Rosenberg S.A., Lopez-Otin C., Samuels Y.; RT "Analysis of the disintegrin-metalloproteinases family reveals ADAM29 RT and ADAM7 are often mutated in melanoma."; RL Hum. Mutat. 32:E2148-E2175(2011). RN [28] RP VARIANTS RAK SER-139 AND TYR-524. RX PubMed=23666529; DOI=10.1093/hmg/ddt207; RA Kono M., Sugiura K., Suganuma M., Hayashi M., Takama H., Suzuki T., RA Matsunaga K., Tomita Y., Akiyama M.; RT "Whole-exome sequencing identifies ADAM10 mutations as a cause of RT reticulate acropigmentation of Kitamura, a clinical entity distinct RT from Dowling-Degos disease."; RL Hum. Mol. Genet. 22:3524-3533(2013). RN [29] 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 [30] {ECO:0000244|PDB:6BDZ, ECO:0000244|PDB:6BE6} RP X-RAY CRYSTALLOGRAPHY (2.80 ANGSTROMS) OF 214-654 IN COMPLEX WITH RP ZINC, CATALYTIC ACTIVITY, FUNCTION, MUTAGENESIS OF GLU-384, RP GLYCOSYLATION AT 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 CC '76-Ala-|-Val-77' to its mature soluble form. Responsible for the CC proteolytical release of soluble JAM3 from endothelial cells CC surface (PubMed:20592283). Responsible for the proteolytic release CC of several other cell-surface proteins, including heparin-binding CC epidermal growth-like factor, ephrin-A2, CD44, CDH2 and for CC constitutive and regulated alpha-secretase cleavage of amyloid CC precursor protein (APP) (PubMed:26686862, PubMed:11786905, CC PubMed:29224781). Contributes to the normal cleavage of the CC cellular prion protein (PubMed:11477090). Involved in the cleavage CC of the adhesion molecule L1 at the cell surface and in released CC membrane vesicles, suggesting a vesicle-based protease activity CC (PubMed:12475894). Controls also the proteolytic processing of CC Notch and mediates lateral inhibition during neurogenesis (By CC 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 CC of the integral membrane proteins CORIN and ITM2B CC (PubMed:19114711, PubMed:21288900). May regulate the EFNA5-EPHA3 CC 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:26686862, ECO:0000269|PubMed:29224781}. CC -!- CATALYTIC ACTIVITY: CC Reaction=Endopeptidase of broad specificity.; EC=3.4.24.81; CC Evidence={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:26686862, CC ECO:0000269|PubMed:29224781}; 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 CC substrates to exerts an inhibitory effect on the cleavage of CC ADAM10 substrates (PubMed:29224781). CC {ECO:0000250|UniProtKB:Q10741, ECO:0000269|PubMed:29224781}. CC -!- SUBUNIT: Interacts with EPHA2 (By similarity). Forms a ternary CC EFNA5-EPHA3-ADAM10 complex mediating EFNA5 extracellular domain CC shedding by ADAM10 which regulates the EFNA5-EPHA3 complex CC internalization and function, the cleavage occurs in trans, with CC ADAM10 and its substrate being on the membranes of opposing cells CC (PubMed:16239146). Interacts with NGF in a divalent cation- CC dependent manner (PubMed:20164177). Interacts with TSPAN14; the CC interaction promotes ADAM10 maturation and cell surface expression CC (PubMed:26668317, PubMed:26686862). Interacts with TSPAN5, CC TSPAN10, TSPAN15, TSPAN17 and TSPAN33; these interactions regulate CC ADAM10 substrate specificity (PubMed:26686862). CC {ECO:0000250|UniProtKB:O35598, ECO:0000269|PubMed:16239146, CC ECO:0000269|PubMed:20164177, ECO:0000269|PubMed:26668317}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:26686862}; CC Single-pass type I membrane protein {ECO:0000305}. Golgi apparatus CC membrane {ECO:0000269|PubMed:12475894}; Single-pass type I CC membrane protein {ECO:0000305}. Note=Is localized in the plasma CC membrane but is predominantly expressed in the Golgi apparatus and CC in released membrane vesicles derived likely from the Golgi. CC {ECO:0000269|PubMed:12475894}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=O14672-1; Sequence=Displayed; CC Name=2; CC IsoId=O14672-2; Sequence=VSP_056401; CC Note=No experimental confirmation available.; CC -!- TISSUE SPECIFICITY: Expressed in spleen, lymph node, thymus, CC peripheral blood leukocyte, bone marrow, cartilage, chondrocytes CC and fetal liver. {ECO:0000269|PubMed:11511685, CC ECO:0000269|PubMed:9016778}. CC -!- INDUCTION: In osteoarthritis affected-cartilage. CC -!- DOMAIN: The propeptide keeps the metalloprotease in a latent form CC via a cysteine switch mechanism. This mechanism may be mediated by CC a highly conserved cysteine (Cys-173) in the propeptide, which CC interacts and neutralizes the zinc-coordinating HEXGHXXGXXHD CC catalytic core of the metalloprotease domain. The dissociation of CC the cysteine from the zinc ion upon the activation-peptide release CC activates the enzyme. {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 CC EFNA5-EPHA3 complex but not the individual proteins (By CC similarity). Both Cys-rich and stalk region are necessary for CC interaction with TSPAN5, TSPAN10, TSPAN14, TSPAN17, TSPAN33 CC (PubMed:26668317). Stalk region is sufficient for interaction with CC TSPAN15 (By similarity). {ECO:0000250|UniProtKB:O35598, CC ECO:0000250|UniProtKB:Q10741, 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) CC [MIM:615537]: A rare cutaneous pigmentation disorder characterized CC by reticulate, slightly depressed, sharply demarcated brown CC macules without hypopigmentation, affecting the dorsa of the hands CC and feet and appearing in the first or second decade of life. The CC macules gradually darken and extend to the proximal regions of the CC extremities. The manifestations tend to progress until middle age, CC after which progression of the eruptions stops. The pigmentary CC augmentation is found on the flexor aspects of the wrists, neck, CC patella and olecranon. Other features include breaks in the CC epidermal ridges on the palms and fingers, palmoplantar pits, CC occasionally plantar keratoderma, and partial alopecia. CC {ECO:0000269|PubMed:23666529}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Alzheimer disease 18 (AD18) [MIM:615590]: A late-onset CC form of Alzheimer disease. Alzheimer disease is a CC neurodegenerative disorder characterized by progressive dementia, CC loss of cognitive abilities, and deposition of fibrillar amyloid CC proteins as intraneuronal neurofibrillary tangles, extracellular CC amyloid plaques and vascular amyloid deposits. The major CC constituents of these plaques are neurotoxic amyloid-beta protein CC 40 and amyloid-beta protein 42, that are produced by the CC proteolysis of the transmembrane APP protein. The cytotoxic C- CC terminal fragments (CTFs) and the caspase-cleaved products, such CC as C31, are also implicated in neuronal death. CC {ECO:0000269|PubMed:19608551, ECO:0000269|PubMed:24055016}. CC Note=Disease susceptibility is associated with variations CC affecting the gene represented in this entry. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/ADAM10ID44397ch15q21.html"; CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; AF009615; AAC51766.1; -; mRNA. DR EMBL; AK300472; BAG62190.1; -; mRNA. DR EMBL; AC018904; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC091046; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; Z48579; CAA88463.1; -; mRNA. DR CCDS; CCDS10167.1; -. [O14672-1] DR RefSeq; NP_001101.1; NM_001110.3. [O14672-1] DR UniGene; Hs.172028; -. DR UniGene; Hs.578508; -. DR UniGene; Hs.745136; -. DR PDB; 1M1I; Model; -; A=207-453. DR 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; 1M1I; -. DR PDBsum; 6BDZ; -. DR PDBsum; 6BE6; -. DR ProteinModelPortal; O14672; -. DR SMR; O14672; -. DR BioGrid; 106616; 38. DR DIP; DIP-39889N; -. DR IntAct; O14672; 11. 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; -. DR iPTMnet; O14672; -. DR PhosphoSitePlus; O14672; -. DR SwissPalm; O14672; -. DR BioMuta; ADAM10; -. DR EPD; O14672; -. DR jPOST; O14672; -. DR MaxQB; O14672; -. DR PaxDb; O14672; -. DR PeptideAtlas; O14672; -. DR PRIDE; O14672; -. DR ProteomicsDB; 48162; -. DR Ensembl; ENST00000260408; ENSP00000260408; ENSG00000137845. [O14672-1] DR GeneID; 102; -. DR KEGG; hsa:102; -. DR UCSC; uc002afd.3; human. [O14672-1] DR CTD; 102; -. DR DisGeNET; 102; -. DR EuPathDB; HostDB:ENSG00000137845.14; -. DR GeneCards; ADAM10; -. DR HGNC; HGNC:188; ADAM10. DR HPA; CAB001709; -. DR HPA; HPA050670; -. DR MalaCards; ADAM10; -. DR MIM; 602192; gene. DR MIM; 615537; phenotype. DR MIM; 615590; phenotype. DR neXtProt; NX_O14672; -. DR OpenTargets; ENSG00000137845; -. DR Orphanet; 178307; Reticulate acropigmentation of Kitamura. DR PharmGKB; PA24505; -. DR eggNOG; KOG3658; Eukaryota. DR eggNOG; ENOG410XQWB; LUCA. DR GeneTree; ENSGT00940000160579; -. DR HOGENOM; HOG000008148; -. DR HOVERGEN; HBG050455; -. DR InParanoid; O14672; -. DR KO; K06704; -. DR OMA; EGFIQTH; -. DR OrthoDB; 162519at2759; -. DR PhylomeDB; O14672; -. DR TreeFam; TF352021; -. DR BioCyc; MetaCyc:ENSG00000137845-MONOMER; -. DR BRENDA; 3.4.24.81; 2681. DR Reactome; R-HSA-1442490; Collagen degradation. DR Reactome; R-HSA-1474228; Degradation of the extracellular matrix. DR Reactome; R-HSA-177929; Signaling by EGFR. DR Reactome; R-HSA-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 ChiTaRS; ADAM10; human. DR GeneWiki; ADAM10; -. DR GenomeRNAi; 102; -. DR PMAP-CutDB; O14672; -. DR PRO; PR:O14672; -. DR Proteomes; UP000005640; Chromosome 15. DR Bgee; ENSG00000137845; Expressed in 242 organ(s), highest expression level in testis. DR ExpressionAtlas; O14672; baseline and differential. DR Genevisible; O14672; HS. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB. DR GO; GO:0043197; C:dendritic spine; IEA:Ensembl. 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:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0043025; C:neuronal cell body; IEA:Ensembl. DR GO; GO:0005634; C:nucleus; ISS:UniProtKB. DR GO; GO:0097038; C:perinuclear endoplasmic reticulum; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl. DR GO; GO:0045211; C:postsynaptic membrane; IEA:Ensembl. DR GO; GO:0035579; C:specific granule membrane; TAS:Reactome. DR GO; GO:0008021; C:synaptic vesicle; IEA:Ensembl. DR GO; GO:0070821; C:tertiary granule membrane; TAS:Reactome. DR GO; GO:0097197; C:tetraspanin-enriched microdomain; IDA:UniProtKB. DR GO; GO:0005802; C:trans-Golgi network; IEA:Ensembl. DR GO; GO:0004175; F:endopeptidase activity; ISS:UniProtKB. DR GO; GO:0005178; F:integrin binding; NAS:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0004222; F:metalloendopeptidase activity; IMP:UniProtKB. DR GO; GO:0008237; F:metallopeptidase activity; IDA:UniProtKB. DR GO; GO:0042803; F:protein homodimerization activity; ISS:UniProtKB. DR GO; GO:0019901; F:protein kinase binding; ISS:UniProtKB. DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW. DR GO; GO:0005102; F:signaling receptor binding; NAS:UniProtKB. DR GO; GO:0034205; P:amyloid-beta formation; IEA:Ensembl. DR GO; GO:0007267; P:cell-cell signaling; NAS:UniProtKB. DR GO; GO:0044267; P:cellular protein metabolic process; TAS:Reactome. DR GO; GO:0051089; P:constitutive protein ectodomain proteolysis; IDA:UniProtKB. 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:0043312; P:neutrophil degranulation; TAS:Reactome. DR GO; GO:0035333; P:Notch receptor processing, ligand-dependent; TAS:Reactome. DR GO; GO:0007219; P:Notch signaling pathway; ISS:UniProtKB. DR GO; GO:0051088; P:PMA-inducible membrane protein ectodomain proteolysis; IMP:BHF-UCL. DR GO; GO:0043065; P:positive regulation of apoptotic process; IEA:Ensembl. 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:0043687; P:post-translational protein modification; TAS:Reactome. 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; IEA:Ensembl. DR GO; GO:0061001; P:regulation of dendritic spine morphogenesis; IEA:Ensembl. DR GO; GO:0098696; P:regulation of neurotransmitter receptor localization to postsynaptic specialization membrane; IEA:Ensembl. DR GO; GO:0097327; P:response to antineoplastic agent; IEA:Ensembl. DR GO; GO:0034612; P:response to tumor necrosis factor; IDA:BHF-UCL. DR GO; GO:0007283; P:spermatogenesis; IEA:Ensembl. DR CDD; cd04270; ZnMc_TACE_like; 1. 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; PTHR11905:SF4; PTHR11905:SF4; 1. DR Pfam; PF00200; Disintegrin; 1. DR Pfam; PF01562; Pep_M12B_propep; 1. DR SMART; SM00050; DISIN; 1. DR SUPFAM; SSF57552; SSF57552; 1. DR PROSITE; PS50215; ADAM_MEPRO; 1. DR PROSITE; PS50214; DISINTEGRIN_2; 1. DR PROSITE; PS00142; ZINC_PROTEASE; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Alzheimer disease; Amyloidosis; KW Cell membrane; Cleavage on pair of basic residues; Complete proteome; KW Direct protein sequencing; Disease mutation; Disulfide bond; KW Glycoprotein; Golgi apparatus; Hydrolase; Membrane; Metal-binding; KW Metalloprotease; Neurodegeneration; Notch signaling pathway; KW Phosphoprotein; Polymorphism; Protease; Reference proteome; KW SH3-binding; Signal; Transmembrane; Transmembrane helix; Zinc; KW Zymogen. FT SIGNAL 1 19 {ECO:0000255}. FT PROPEP 20 213 {ECO:0000250|UniProtKB:Q10741}. FT /FTId=PRO_0000029066. FT CHAIN 214 748 Disintegrin and metalloproteinase domain- FT containing protein 10. FT /FTId=PRO_0000029067. FT TOPO_DOM 20 672 Extracellular. {ECO:0000255}. FT TRANSMEM 673 693 Helical. {ECO:0000255}. FT TOPO_DOM 694 748 Cytoplasmic. {ECO:0000255}. FT DOMAIN 220 456 Peptidase M12B. {ECO:0000255|PROSITE- FT ProRule:PRU00276}. FT DOMAIN 457 551 Disintegrin. {ECO:0000255|PROSITE- FT ProRule:PRU00068}. FT MOTIF 171 178 Cysteine switch. {ECO:0000250}. FT MOTIF 708 715 SH3-binding. {ECO:0000255}. FT MOTIF 722 728 SH3-binding. {ECO:0000255}. FT COMPBIAS 555 673 Cys-rich. {ECO:0000305}. FT ACT_SITE 384 384 {ECO:0000269|PubMed:29224781}. FT METAL 173 173 Zinc; in inhibited form. FT {ECO:0000250|UniProtKB:P03956}. FT METAL 383 383 Zinc; via tele nitrogen; catalytic. FT {ECO:0000244|PDB:6BDZ, FT ECO:0000244|PDB:6BE6, FT ECO:0000269|PubMed:24055016, FT ECO:0000269|PubMed:29224781}. FT METAL 387 387 Zinc; via tele nitrogen; catalytic. FT {ECO:0000244|PDB:6BE6, FT ECO:0000269|PubMed:29224781}. FT METAL 393 393 Zinc; via tele nitrogen; catalytic. FT {ECO:0000244|PDB:6BDZ, FT ECO:0000244|PDB:6BE6, FT ECO:0000269|PubMed:24055016, FT ECO:0000269|PubMed:29224781}. FT SITE 213 214 Cleavage; by furin and PCSK7. FT {ECO:0000250|UniProtKB:Q10741}. FT MOD_RES 719 719 Phosphothreonine; by FAM20C. FT {ECO:0000244|PubMed:23186163, FT ECO:0000244|PubMed:24275569, FT ECO:0000269|PubMed:26091039}. FT CARBOHYD 267 267 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 278 278 N-linked (GlcNAc...) asparagine. FT {ECO:0000244|PDB:6BDZ, FT ECO:0000244|PDB:6BE6, FT ECO:0000269|PubMed:16263699, FT ECO:0000269|PubMed:19159218, FT ECO:0000269|PubMed:19349973, FT ECO:0000269|PubMed:29224781}. FT CARBOHYD 439 439 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 551 551 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 222 313 {ECO:0000244|PDB:6BDZ, FT ECO:0000244|PDB:6BE6, FT ECO:0000269|PubMed:29224781}. FT DISULFID 344 451 {ECO:0000244|PDB:6BDZ, FT ECO:0000244|PDB:6BE6, FT ECO:0000269|PubMed:29224781}. FT DISULFID 399 435 {ECO:0000244|PDB:6BDZ, FT ECO:0000244|PDB:6BE6, FT ECO:0000269|PubMed:29224781}. FT DISULFID 460 495 {ECO:0000244|PDB:6BDZ, FT ECO:0000244|PDB:6BE6, FT ECO:0000269|PubMed:29224781}. FT DISULFID 471 484 {ECO:0000244|PDB:6BDZ, FT ECO:0000244|PDB:6BE6, FT ECO:0000269|PubMed:29224781}. FT DISULFID 473 479 {ECO:0000244|PDB:6BDZ, FT ECO:0000244|PDB:6BE6, FT ECO:0000269|PubMed:29224781}. FT DISULFID 483 515 {ECO:0000244|PDB:6BDZ, FT ECO:0000244|PDB:6BE6, FT ECO:0000269|PubMed:29224781}. FT DISULFID 503 511 {ECO:0000244|PDB:6BDZ, FT ECO:0000244|PDB:6BE6, FT ECO:0000269|PubMed:29224781}. FT DISULFID 510 536 {ECO:0000244|PDB:6BDZ, FT ECO:0000244|PDB:6BE6, FT ECO:0000269|PubMed:29224781}. FT DISULFID 524 543 {ECO:0000244|PDB:6BDZ, FT ECO:0000244|PDB:6BE6, FT ECO:0000269|PubMed:29224781}. FT DISULFID 530 562 {ECO:0000244|PDB:6BDZ, FT ECO:0000244|PDB:6BE6, FT ECO:0000269|PubMed:29224781}. FT DISULFID 555 567 {ECO:0000244|PDB:6BDZ, FT ECO:0000244|PDB:6BE6, FT ECO:0000269|PubMed:29224781}. FT DISULFID 572 598 {ECO:0000244|PDB:6BDZ, FT ECO:0000244|PDB:6BE6, FT ECO:0000269|PubMed:29224781}. FT DISULFID 580 607 {ECO:0000244|PDB:6BDZ, FT ECO:0000244|PDB:6BE6, FT ECO:0000269|PubMed:29224781}. FT DISULFID 582 597 {ECO:0000244|PDB:6BDZ, FT ECO:0000244|PDB:6BE6, FT ECO:0000269|PubMed:29224781}. FT DISULFID 594 639 {ECO:0000244|PDB:6BDZ, FT ECO:0000244|PDB:6BE6, FT ECO:0000269|PubMed:29224781}. FT DISULFID 632 645 {ECO:0000244|PDB:6BDZ, FT ECO:0000244|PDB:6BE6, FT ECO:0000269|PubMed:29224781}. FT VAR_SEQ 19 319 Missing (in isoform 2). FT {ECO:0000303|PubMed:14702039}. FT /FTId=VSP_056401. FT VARIANT 139 139 P -> S (in RAK; dbSNP:rs483352912). FT {ECO:0000269|PubMed:23666529}. FT /FTId=VAR_070907. FT VARIANT 170 170 Q -> H (in AD18; associated with disease FT susceptibility; significantly attenuates FT alpha-secretase activity of the enzyme; FT shifts APP processing toward beta- FT secretase-mediated cleavage resulting in FT enhanced amyloid-beta plaque load and FT reactive gliosis; dbSNP:rs61751103). FT {ECO:0000269|PubMed:19608551, FT ECO:0000269|PubMed:24055016}. FT /FTId=VAR_070908. FT VARIANT 176 176 H -> Y (in a cutaneous metastatic FT melanoma sample; somatic mutation; FT dbSNP:rs267604273). FT {ECO:0000269|PubMed:21618342}. FT /FTId=VAR_066309. FT VARIANT 181 181 R -> G (in AD18; associated with disease FT susceptibility; significantly attenuates FT alpha-secretase activity of the enzyme; FT shifts APP processing toward beta- FT secretase-mediated cleavage resulting in FT enhanced amyloid-beta plaque load and FT reactive gliosis; dbSNP:rs145518263). FT {ECO:0000269|PubMed:19608551, FT ECO:0000269|PubMed:24055016}. FT /FTId=VAR_070909. FT VARIANT 524 524 C -> Y (in RAK; dbSNP:rs483352916). FT {ECO:0000269|PubMed:23666529}. FT /FTId=VAR_070910. FT MUTAGEN 384 384 E->A: Abrogates APP cleavage. Reduces FT Notch signaling. FT {ECO:0000269|PubMed:29224781}. FT CONFLICT 162 162 N -> SERLKLRLRKLMSLELWTSCCLPCALLLHSWKKAVN FT SHCLYFKDFWGFSEIY (in Ref. 2; CAA88463). FT {ECO:0000305}. FT CONFLICT 212 212 K -> R (in Ref. 2; CAA88463). FT {ECO:0000305}. FT CONFLICT 296 296 G -> S (in Ref. 2; CAA88463). FT {ECO:0000305}. FT STRAND 219 228 {ECO:0000244|PDB:6BE6}. FT HELIX 230 236 {ECO:0000244|PDB:6BE6}. FT HELIX 239 258 {ECO:0000244|PDB:6BE6}. FT STRAND 269 277 {ECO:0000244|PDB:6BE6}. FT HELIX 280 284 {ECO:0000244|PDB:6BE6}. FT HELIX 297 305 {ECO:0000244|PDB:6BE6}. FT STRAND 313 322 {ECO:0000244|PDB:6BE6}. FT HELIX 324 326 {ECO:0000244|PDB:6BE6}. FT STRAND 329 331 {ECO:0000244|PDB:6BE6}. FT STRAND 336 338 {ECO:0000244|PDB:6BE6}. FT STRAND 348 350 {ECO:0000244|PDB:6BE6}. FT STRAND 359 367 {ECO:0000244|PDB:6BE6}. FT HELIX 374 388 {ECO:0000244|PDB:6BE6}. FT TURN 397 399 {ECO:0000244|PDB:6BE6}. FT HELIX 401 403 {ECO:0000244|PDB:6BE6}. FT HELIX 407 411 {ECO:0000244|PDB:6BE6}. FT HELIX 428 430 {ECO:0000244|PDB:6BE6}. FT HELIX 434 447 {ECO:0000244|PDB:6BE6}. FT HELIX 448 450 {ECO:0000244|PDB:6BE6}. FT STRAND 462 464 {ECO:0000244|PDB:6BE6}. FT TURN 476 478 {ECO:0000244|PDB:6BE6}. FT TURN 491 495 {ECO:0000244|PDB:6BE6}. FT TURN 505 507 {ECO:0000244|PDB:6BE6}. FT STRAND 509 511 {ECO:0000244|PDB:6BE6}. FT STRAND 523 525 {ECO:0000244|PDB:6BE6}. FT STRAND 529 531 {ECO:0000244|PDB:6BE6}. FT STRAND 553 555 {ECO:0000244|PDB:6BDZ}. FT TURN 556 559 {ECO:0000244|PDB:6BE6}. FT STRAND 560 563 {ECO:0000244|PDB:6BE6}. FT STRAND 566 569 {ECO:0000244|PDB:6BE6}. FT HELIX 571 575 {ECO:0000244|PDB:6BE6}. FT STRAND 577 580 {ECO:0000244|PDB:6BE6}. FT STRAND 597 600 {ECO:0000244|PDB:6BE6}. FT HELIX 604 606 {ECO:0000244|PDB:6BE6}. FT HELIX 614 617 {ECO:0000244|PDB:6BE6}. FT STRAND 630 632 {ECO:0000244|PDB:6BDZ}. FT TURN 633 636 {ECO:0000244|PDB:6BE6}. FT STRAND 637 639 {ECO:0000244|PDB:6BE6}. FT STRAND 645 647 {ECO:0000244|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 //