Disintegrin and metalloproteinase domain-containing protein 17

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>Functionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityⁱ

• Narrow endopeptidase specificity. Cleaves Pro-Leu-Ala-Gln-Ala-|-Val-Arg-Ser-Ser-Ser in the membrane-bound, 26-kDa form of tumor necrosis factor alpha (TNF-alpha). Similarly cleaves other membrane-anchored, cell-surface proteins to 'shed' the extracellular domains.3 Publications

  Manual assertion based on experiment inⁱ

  • Ref.5

    "Tumor necrosis factor-alpha converting enzyme/ADAM 17 mediates MUC1 shedding."
    Thathiah A., Blobel C.P., Carson D.D.
    J. Biol. Chem. 278:3386-3394(2003) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH MUC1.
  • Ref.9

    "Junctional adhesion molecule-C is a soluble mediator of angiogenesis."
    Rabquer B.J., Amin M.A., Teegala N., Shaheen M.K., Tsou P.S., Ruth J.H., Lesch C.A., Imhof B.A., Koch A.E.
    J. Immunol. 185:1777-1785(2010) [PubMed] [Europe PMC] [Abstract]

    Cited for: ROLE IN PROTEOLYTICAL RELEASE OF JAM3.
  • Ref.17

    "TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein."
    Heurich A., Hofmann-Winkler H., Gierer S., Liepold T., Jahn O., Poehlmann S.
    J. Virol. 88:1293-1307(2014) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CATALYTIC ACTIVITY.

  EC:3.4.24.86

<p>This subsection of the 'Function' section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactorⁱ

Sites

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functionⁱ

• endopeptidase activity Source: UniProtKB <p>Inferred from Mutant Phenotype</p> <p>Describes annotations that are concluded from looking at variations or changes in a gene product such as mutations or abnormal levels and includes techniques such as knockouts, overexpression, anti-sense experiments and use of specific protein inhibitors.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#imp">GO evidence code guide</a></p> Inferred from mutant phenotypeⁱ
  • "TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis."
    Kleinberger G., Yamanishi Y., Suarez-Calvet M., Czirr E., Lohmann E., Cuyvers E., Struyfs H., Pettkus N., Wenninger-Weinzierl A., Mazaheri F., Tahirovic S., Lleo A., Alcolea D., Fortea J., Willem M., Lammich S., Molinuevo J.L., Sanchez-Valle R.

    , Antonell A., Ramirez A., Heneka M.T., Sleegers K., van der Zee J., Martin J.J., Engelborghs S., Demirtas-Tatlidede A., Zetterberg H., Van Broeckhoven C., Gurvit H., Wyss-Coray T., Hardy J., Colonna M., Haass C.
    Sci. Transl. Med. 6:243RA86-243RA86(2014) [PubMed] [Europe PMC] [Abstract]
• integrin binding Source: BHF-UCL <p>Inferred from Physical Interaction</p> <p>Covers physical interactions between the gene product of interest and another molecule (or ion, or complex).</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ipi">GO evidence code guide</a></p> Inferred from physical interactionⁱ
  • "Integrin alpha5beta1 and ADAM-17 interact in vitro and co-localize in migrating HeLa cells."
    Bax D.V., Messent A.J., Tart J., van Hoang M., Kott J., Maciewicz R.A., Humphries M.J.
    J Biol Chem 279:22377-22386(2004) [PubMed] [Europe PMC] [Abstract]
• interleukin-6 receptor binding Source: BHF-UCLInferred from physical interactionⁱ
  • "Bacterial induction of TNF-alpha converting enzyme expression and IL-6 receptor alpha shedding regulates airway inflammatory signaling."
    Gomez M.I., Sokol S.H., Muir A.B., Soong G., Bastien J., Prince A.S.
    J Immunol 175:1930-1936(2005) [PubMed] [Europe PMC] [Abstract]
• metal ion binding Source: UniProtKB-KW
• metalloendopeptidase activity Source: UniProtKB <p>Inferred from Direct Assay</p> <p>Used to indicate a direct assay for the function, process or component indicated by the GO term.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ida">GO evidence code guide</a></p> Inferred from direct assayⁱ
  • Ref.15

    "The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality."
    Boskovski M.T., Yuan S., Pedersen N.B., Goth C.K., Makova S., Clausen H., Brueckner M., Khokha M.K.
    Nature 504:456-459(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• metallopeptidase activity Source: BHF-UCLInferred from direct assayⁱ
  • "Catalytic activity of ADAM8, ADAM15, and MDC-L (ADAM28) on synthetic peptide substrates and in ectodomain cleavage of CD23."
    Fourie A.M., Coles F., Moreno V., Karlsson L.
    J Biol Chem 278:30469-30477(2003) [PubMed] [Europe PMC] [Abstract]
• Notch binding Source: UniProtKBInferred from direct assayⁱ
  • Ref.15

    "The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality."
    Boskovski M.T., Yuan S., Pedersen N.B., Goth C.K., Makova S., Clausen H., Brueckner M., Khokha M.K.
    Nature 504:456-459(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• PDZ domain binding Source: BHF-UCLInferred from physical interactionⁱ
  • "Evidence for regulation of the tumor necrosis factor alpha-convertase (TACE) by protein-tyrosine phosphatase PTPH1."
    Zheng Y., Schlondorff J., Blobel C.P.
    J Biol Chem 277:42463-42470(2002) [PubMed] [Europe PMC] [Abstract]
• peptidase activity Source: ARUK-UCL <p>Traceable Author Statement</p> <p>Used for information from review articles where the original experiments are traceable through that article and also for information from text books or dictionaries.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#tas">GO evidence code guide</a></p> Traceable author statementⁱ
  • "Tumor necrosis factor alpha: a link between neuroinflammation and excitotoxicity."
    Olmos G., Llado J.
    Mediators Inflamm 2014:861231-861231(2014) [PubMed] [Europe PMC] [Abstract]
• SH3 domain binding Source: UniProtKB-KW

GO - Biological processⁱ

• B cell differentiation Source: BHF-UCL <p>Inferred from Sequence or Structural Similarity<br />Used for any analysis based on sequence alignment, structure comparison, or evaluation of sequence features such as composition.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iss">GO evidence code guide</a></p> Inferred from sequence or structural similarityⁱ
  • "Characterization of the cDNA and gene for mouse tumour necrosis factor alpha converting enzyme (TACE/ADAM17) and its location to mouse chromosome 12 and human chromosome 2p25."
    Cerretti D.P., Poindexter K., Castner B.J., Means G., Copeland N.G., Gilbert D.J., Jenkins N.A., Black R.A., Nelson N.
    Cytokine 11:541-551(1999) [PubMed] [Europe PMC] [Abstract]
• cell adhesion Source: BHF-UCLInferred from direct assayⁱ
  • "Integrin alpha5beta1 and ADAM-17 interact in vitro and co-localize in migrating HeLa cells."
    Bax D.V., Messent A.J., Tart J., van Hoang M., Kott J., Maciewicz R.A., Humphries M.J.
    J Biol Chem 279:22377-22386(2004) [PubMed] [Europe PMC] [Abstract]
• cell adhesion mediated by integrin Source: BHF-UCLInferred from direct assayⁱ
  • "Integrin alpha5beta1 and ADAM-17 interact in vitro and co-localize in migrating HeLa cells."
    Bax D.V., Messent A.J., Tart J., van Hoang M., Kott J., Maciewicz R.A., Humphries M.J.
    J Biol Chem 279:22377-22386(2004) [PubMed] [Europe PMC] [Abstract]
• cell motility Source: BHF-UCLInferred from sequence or structural similarityⁱ
  • "Characterization of the cDNA and gene for mouse tumour necrosis factor alpha converting enzyme (TACE/ADAM17) and its location to mouse chromosome 12 and human chromosome 2p25."
    Cerretti D.P., Poindexter K., Castner B.J., Means G., Copeland N.G., Gilbert D.J., Jenkins N.A., Black R.A., Nelson N.
    Cytokine 11:541-551(1999) [PubMed] [Europe PMC] [Abstract]
• cellular response to high density lipoprotein particle stimulus Source: BHF-UCLInferred from direct assayⁱ
  • "HDLs activate ADAM17-dependent shedding."
    Tellier E., Canault M., Poggi M., Bonardo B., Nicolay A., Alessi M.C., Nalbone G., Peiretti F.
    J Cell Physiol 214:687-693(2008) [PubMed] [Europe PMC] [Abstract]
• defense response to Gram-positive bacterium Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "Bacterial induction of TNF-alpha converting enzyme expression and IL-6 receptor alpha shedding regulates airway inflammatory signaling."
    Gomez M.I., Sokol S.H., Muir A.B., Soong G., Bastien J., Prince A.S.
    J Immunol 175:1930-1936(2005) [PubMed] [Europe PMC] [Abstract]
• epidermal growth factor receptor signaling pathway Source: BHF-UCLInferred from direct assayⁱ
  • "TACE cleavage of proamphiregulin regulates GPCR-induced proliferation and motility of cancer cells."
    Gschwind A., Hart S., Fischer O.M., Ullrich A.
    EMBO J 22:2411-2421(2003) [PubMed] [Europe PMC] [Abstract]
• germinal center formation Source: BHF-UCLInferred from sequence or structural similarityⁱ
  • "Characterization of the cDNA and gene for mouse tumour necrosis factor alpha converting enzyme (TACE/ADAM17) and its location to mouse chromosome 12 and human chromosome 2p25."
    Cerretti D.P., Poindexter K., Castner B.J., Means G., Copeland N.G., Gilbert D.J., Jenkins N.A., Black R.A., Nelson N.
    Cytokine 11:541-551(1999) [PubMed] [Europe PMC] [Abstract]
• membrane protein ectodomain proteolysis Source: BHF-UCLInferred from direct assayⁱ
  • "Tumor necrosis factor-alpha-converting enzyme controls surface expression of c-Kit and survival of embryonic stem cell-derived mast cells."
    Cruz A.C., Frank B.T., Edwards S.T., Dazin P.F., Peschon J.J., Fang K.C.
    J Biol Chem 279:5612-5620(2004) [PubMed] [Europe PMC] [Abstract]
  • "Evidence for a role of ADAM17 (TACE) in the regulation of platelet glycoprotein V."
    Rabie T., Strehl A., Ludwig A., Nieswandt B.
    J Biol Chem 280:14462-14468(2005) [PubMed] [Europe PMC] [Abstract]
  • "The shedding activity of ADAM17 is sequestered in lipid rafts."
    Tellier E., Canault M., Rebsomen L., Bonardo B., Juhan-Vague I., Nalbone G., Peiretti F.
    Exp Cell Res 312:3969-3980(2006) [PubMed] [Europe PMC] [Abstract]
  • "HDLs activate ADAM17-dependent shedding."
    Tellier E., Canault M., Poggi M., Bonardo B., Nicolay A., Alessi M.C., Nalbone G., Peiretti F.
    J Cell Physiol 214:687-693(2008) [PubMed] [Europe PMC] [Abstract]
  • "Tumor-associated MICA is shed by ADAM proteases."
    Waldhauer I., Goehlsdorf D., Gieseke F., Weinschenk T., Wittenbrink M., Ludwig A., Stevanovic S., Rammensee H.G., Steinle A.
    Cancer Res 68:6368-6376(2008) [PubMed] [Europe PMC] [Abstract]
  • Ref.2

    "A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells."
    Black R.A., Rauch C.T., Kozlosky C.J., Peschon J.J., Slack J.L., Wolfson M.F., Castner B.J., Stocking K.L., Reddy P., Srinivasan S., Nelson N., Bioani N., Schooley K.A., Gerhart M., Davis R., Fitzner J.N., Johnson R.S., Paxton R.J., March C.J., Cerretti D.P.
    Nature 385:729-733(1997) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B).
  • Ref.3

    "TNF-alpha convertase enzyme from human arthritis-affected cartilage: isolation of cDNA by differential display, expression of the active enzyme, and regulation of TNF-alpha."
    Patel I.R., Attur M.G., Patel R.N., Stuchin S.A., Abagyan R.A., Abramson S.B., Amin A.R.
    J. Immunol. 160:4570-4579(1998) [PubMed] [Europe PMC] [Abstract]

    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
• membrane protein intracellular domain proteolysis Source: Reactome
• negative regulation of cold-induced thermogenesis Source: YuBioLabInferred from sequence or structural similarityⁱ
  • "Deficiency of TNFalpha converting enzyme (TACE/ADAM17) causes a lean, hypermetabolic phenotype in mice."
    Gelling R.W., Yan W., Al-Noori S., Pardini A., Morton G.J., Ogimoto K., Schwartz M.W., Dempsey P.J.
    Endocrinology 149:6053-6064(2008) [PubMed] [Europe PMC] [Abstract]
• negative regulation of transforming growth factor beta receptor signaling pathway Source: UniProtKBInferred from mutant phenotypeⁱ
  • "ADAM17 (TACE) regulates TGFbeta signaling through the cleavage of vasorin."
    Malapeira J., Esselens C., Bech-Serra J.J., Canals F., Arribas J.
    Oncogene 30:1912-1922(2011) [PubMed] [Europe PMC] [Abstract]
• neutrophil mediated immunity Source: BHF-UCL <p>Inferred by Curator</p> <p>Used for cases where an annotation is not supported by any evidence but can be reasonably inferred by a curator from other GO annotations for which evidence<br />is available.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#ic">GO evidence code guide</a></p> Inferred by curatorⁱ
  • "Bacterial induction of TNF-alpha converting enzyme expression and IL-6 receptor alpha shedding regulates airway inflammatory signaling."
    Gomez M.I., Sokol S.H., Muir A.B., Soong G., Bastien J., Prince A.S.
    J Immunol 175:1930-1936(2005) [PubMed] [Europe PMC] [Abstract]
• Notch receptor processing Source: UniProtKBInferred from direct assayⁱ
  • Ref.15

    "The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality."
    Boskovski M.T., Yuan S., Pedersen N.B., Goth C.K., Makova S., Clausen H., Brueckner M., Khokha M.K.
    Nature 504:456-459(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• Notch signaling pathway Source: GO_Central <p>Inferred from Biological aspect of Ancestor</p> <p>A type of phylogenetic evidence whereby an aspect of a descendent is inferred through the characterization of an aspect of a ancestral gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iba">GO evidence code guide</a></p> Inferred from biological aspect of ancestorⁱ
  • "Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium."
    Gaudet P., Livstone M.S., Lewis S.E., Thomas P.D.
    Brief Bioinform 12:449-462(2011) [PubMed] [Europe PMC] [Abstract]
• positive regulation of blood vessel endothelial cell migration Source: BHF-UCLInferred from direct assayⁱ
  • "MiR-152 reduces human umbilical vein endothelial cell proliferation and migration by targeting ADAM17."
    Wu Y., Huang A., Li T., Su X., Ding H., Li H., Qin X., Hou L., Zhao Q., Ge X., Fang T., Wang R., Gao C., Li J., Shao N.
    FEBS Lett 588:2063-2069(2014) [PubMed] [Europe PMC] [Abstract]
• positive regulation of cell growth Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "The role of CXCL16 and its processing metalloproteinases ADAM10 and ADAM17 in the proliferation and migration of human mesangial cells."
    Schramme A., Abdel-Bakky M.S., Kampfer-Kolb N., Pfeilschifter J., Gutwein P.
    Biochem Biophys Res Commun 370:311-316(2008) [PubMed] [Europe PMC] [Abstract]
• positive regulation of cell migration Source: ARUK-UCLInferred from direct assayⁱ
  • "MiR-338-3p inhibits the proliferation and migration of gastric cancer cells by targeting ADAM17."
    Chen J.T., Yao K.H., Hua L., Zhang L.P., Wang C.Y., Zhang J.J.
    Int J Clin Exp Pathol 8:10922-10928(2015) [PubMed] [Europe PMC] [Abstract]
• positive regulation of cell population proliferation Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "The role of CXCL16 and its processing metalloproteinases ADAM10 and ADAM17 in the proliferation and migration of human mesangial cells."
    Schramme A., Abdel-Bakky M.S., Kampfer-Kolb N., Pfeilschifter J., Gutwein P.
    Biochem Biophys Res Commun 370:311-316(2008) [PubMed] [Europe PMC] [Abstract]
• positive regulation of cellular component movement Source: BHF-UCLInferred from sequence or structural similarityⁱ
  • "Characterization of the cDNA and gene for mouse tumour necrosis factor alpha converting enzyme (TACE/ADAM17) and its location to mouse chromosome 12 and human chromosome 2p25."
    Cerretti D.P., Poindexter K., Castner B.J., Means G., Copeland N.G., Gilbert D.J., Jenkins N.A., Black R.A., Nelson N.
    Cytokine 11:541-551(1999) [PubMed] [Europe PMC] [Abstract]
• positive regulation of chemokine production Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "Bacterial induction of TNF-alpha converting enzyme expression and IL-6 receptor alpha shedding regulates airway inflammatory signaling."
    Gomez M.I., Sokol S.H., Muir A.B., Soong G., Bastien J., Prince A.S.
    J Immunol 175:1930-1936(2005) [PubMed] [Europe PMC] [Abstract]
• positive regulation of cyclin-dependent protein serine/threonine kinase activity Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "UVA-induced cell cycle progression is mediated by a disintegrin and metalloprotease/epidermal growth factor receptor/AKT/Cyclin D1 pathways in keratinocytes."
    He Y.Y., Council S.E., Feng L., Chignell C.F.
    Cancer Res 68:3752-3758(2008) [PubMed] [Europe PMC] [Abstract]
• positive regulation of epidermal growth factor-activated receptor activity Source: BHF-UCLInferred from direct assayⁱ
  • "UVA-induced cell cycle progression is mediated by a disintegrin and metalloprotease/epidermal growth factor receptor/AKT/Cyclin D1 pathways in keratinocytes."
    He Y.Y., Council S.E., Feng L., Chignell C.F.
    Cancer Res 68:3752-3758(2008) [PubMed] [Europe PMC] [Abstract]
• positive regulation of G1/S transition of mitotic cell cycle Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "UVA-induced cell cycle progression is mediated by a disintegrin and metalloprotease/epidermal growth factor receptor/AKT/Cyclin D1 pathways in keratinocytes."
    He Y.Y., Council S.E., Feng L., Chignell C.F.
    Cancer Res 68:3752-3758(2008) [PubMed] [Europe PMC] [Abstract]
• positive regulation of leukocyte chemotaxis Source: BHF-UCLInferred by curatorⁱ
  • "Bacterial induction of TNF-alpha converting enzyme expression and IL-6 receptor alpha shedding regulates airway inflammatory signaling."
    Gomez M.I., Sokol S.H., Muir A.B., Soong G., Bastien J., Prince A.S.
    J Immunol 175:1930-1936(2005) [PubMed] [Europe PMC] [Abstract]
• positive regulation of protein phosphorylation Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "Transforming growth factor beta engages TACE and ErbB3 to activate phosphatidylinositol-3 kinase/Akt in ErbB2-overexpressing breast cancer and desensitizes cells to trastuzumab."
    Wang S.E., Xiang B., Guix M., Olivares M.G., Parker J., Chung C.H., Pandiella A., Arteaga C.L.
    Mol Cell Biol 28:5605-5620(2008) [PubMed] [Europe PMC] [Abstract]
• positive regulation of T cell chemotaxis Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "The role of CXCL16 and its processing metalloproteinases ADAM10 and ADAM17 in the proliferation and migration of human mesangial cells."
    Schramme A., Abdel-Bakky M.S., Kampfer-Kolb N., Pfeilschifter J., Gutwein P.
    Biochem Biophys Res Commun 370:311-316(2008) [PubMed] [Europe PMC] [Abstract]
• positive regulation of transforming growth factor beta receptor signaling pathway Source: BHF-UCLInferred from sequence or structural similarityⁱ
  • "Characterization of the cDNA and gene for mouse tumour necrosis factor alpha converting enzyme (TACE/ADAM17) and its location to mouse chromosome 12 and human chromosome 2p25."
    Cerretti D.P., Poindexter K., Castner B.J., Means G., Copeland N.G., Gilbert D.J., Jenkins N.A., Black R.A., Nelson N.
    Cytokine 11:541-551(1999) [PubMed] [Europe PMC] [Abstract]
• positive regulation of tumor necrosis factor-mediated signaling pathway Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "MiR-152 reduces human umbilical vein endothelial cell proliferation and migration by targeting ADAM17."
    Wu Y., Huang A., Li T., Su X., Ding H., Li H., Qin X., Hou L., Zhao Q., Ge X., Fang T., Wang R., Gao C., Li J., Shao N.
    FEBS Lett 588:2063-2069(2014) [PubMed] [Europe PMC] [Abstract]
• positive regulation of vascular endothelial cell proliferation Source: BHF-UCLInferred from direct assayⁱ
  • "MiR-152 reduces human umbilical vein endothelial cell proliferation and migration by targeting ADAM17."
    Wu Y., Huang A., Li T., Su X., Ding H., Li H., Qin X., Hou L., Zhao Q., Ge X., Fang T., Wang R., Gao C., Li J., Shao N.
    FEBS Lett 588:2063-2069(2014) [PubMed] [Europe PMC] [Abstract]
• proteolysis Source: UniProtKBInferred from direct assayⁱ
  • Ref.17

    "TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein."
    Heurich A., Hofmann-Winkler H., Gierer S., Liepold T., Jahn O., Poehlmann S.
    J. Virol. 88:1293-1307(2014) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION, CATALYTIC ACTIVITY.
• receptor transactivation Source: BHF-UCLInferred from mutant phenotypeⁱ
  • "EGF receptor transactivation and PI3-kinase mediate stimulation of ERK by alpha(2A)-adrenoreceptor in intestinal epithelial cells: a role in wound healing."
    Buffin-Meyer B., Crassous P.A., Delage C., Denis C., Schaak S., Paris H.
    Eur J Pharmacol 574:85-93(2007) [PubMed] [Europe PMC] [Abstract]
• regulation of mast cell apoptotic process Source: BHF-UCLInferred from sequence or structural similarityⁱ
  • "Characterization of the cDNA and gene for mouse tumour necrosis factor alpha converting enzyme (TACE/ADAM17) and its location to mouse chromosome 12 and human chromosome 2p25."
    Cerretti D.P., Poindexter K., Castner B.J., Means G., Copeland N.G., Gilbert D.J., Jenkins N.A., Black R.A., Nelson N.
    Cytokine 11:541-551(1999) [PubMed] [Europe PMC] [Abstract]
• response to drug Source: BHF-UCLInferred from sequence or structural similarityⁱ
  • "Characterization of the cDNA and gene for mouse tumour necrosis factor alpha converting enzyme (TACE/ADAM17) and its location to mouse chromosome 12 and human chromosome 2p25."
    Cerretti D.P., Poindexter K., Castner B.J., Means G., Copeland N.G., Gilbert D.J., Jenkins N.A., Black R.A., Nelson N.
    Cytokine 11:541-551(1999) [PubMed] [Europe PMC] [Abstract]
• response to hypoxia Source: BHF-UCLInferred from direct assayⁱ
  • "Tumor necrosis factor-alpha converting enzyme in the human placenta throughout gestation."
    Hung T.H., Chen S.F., Hsieh C.C., Hsu J.J., Li M.J., Yeh Y.L., Hsieh T.T.
    Reprod Sci 15:195-209(2008) [PubMed] [Europe PMC] [Abstract]
• response to lipopolysaccharide Source: BHF-UCLInferred from direct assayⁱ
  • "Interleukin-10 regulates TNF-alpha-converting enzyme (TACE/ADAM-17) involving a TIMP-3 dependent and independent mechanism."
    Brennan F.M., Green P., Amjadi P., Robertshaw H.J., Alvarez-Iglesias M., Takata M.
    Eur J Immunol 38:1106-1117(2008) [PubMed] [Europe PMC] [Abstract]
• spleen development Source: BHF-UCLInferred from sequence or structural similarityⁱ
  • "Characterization of the cDNA and gene for mouse tumour necrosis factor alpha converting enzyme (TACE/ADAM17) and its location to mouse chromosome 12 and human chromosome 2p25."
    Cerretti D.P., Poindexter K., Castner B.J., Means G., Copeland N.G., Gilbert D.J., Jenkins N.A., Black R.A., Nelson N.
    Cytokine 11:541-551(1999) [PubMed] [Europe PMC] [Abstract]
• T cell differentiation in thymus Source: BHF-UCLInferred from sequence or structural similarityⁱ
  • "Characterization of the cDNA and gene for mouse tumour necrosis factor alpha converting enzyme (TACE/ADAM17) and its location to mouse chromosome 12 and human chromosome 2p25."
    Cerretti D.P., Poindexter K., Castner B.J., Means G., Copeland N.G., Gilbert D.J., Jenkins N.A., Black R.A., Nelson N.
    Cytokine 11:541-551(1999) [PubMed] [Europe PMC] [Abstract]
• tumor necrosis factor-mediated signaling pathway Source: Reactome
• wound healing, spreading of epidermal cells Source: BHF-UCL <p>Inferred from Expression Pattern</p> <p>Covers cases where the annotation is inferred from the timing or location of expression of a gene.</p> <p>More information in the <a href="http://geneontology.org/page/guide%2Dgo%2Devidence%2Dcodes#iep">GO evidence code guide</a></p> Inferred from expression patternⁱ
  • "Integrin alpha5beta1 and ADAM-17 interact in vitro and co-localize in migrating HeLa cells."
    Bax D.V., Messent A.J., Tart J., van Hoang M., Kott J., Maciewicz R.A., Humphries M.J.
    J Biol Chem 279:22377-22386(2004) [PubMed] [Europe PMC] [Abstract]

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsⁱ

Enzyme and pathway databases

Protein family/group databases

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyⁱ

Organism-specific databases

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationⁱ

Topology

Keywords - Cellular componentⁱ

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechⁱ

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseaseⁱ

Organism-specific databases

Miscellaneous databases

Chemistry databases

Genetic variation databases

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingⁱ

Molecule processing

Amino acid modifications

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>Post-translational modificationⁱ

Keywords - PTMⁱ

Proteomic databases

PTM databases

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressionⁱ

<p>This subsection of the 'Expression' section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms. By default, the information is derived from experiments at the mRNA level, unless specified 'at protein level'.<br></br>Examples: <a href="http://www.uniprot.org/uniprot/P92958#expression">P92958</a>, <a href="http://www.uniprot.org/uniprot/Q8TDN4#expression">Q8TDN4</a>, <a href="http://www.uniprot.org/uniprot/O14734#expression">O14734</a><p><a href='/help/tissue_specificity' target='_top'>More...</a></p>Tissue specificityⁱ

<p>This subsection of the 'Expression' section reports the experimentally proven effects of inducers and repressors (usually chemical compounds or environmental factors) on the level of protein (or mRNA) expression (up-regulation, down-regulation, constitutive expression).<p><a href='/help/induction' target='_top'>More...</a></p>Inductionⁱ

Gene expression databases

Organism-specific databases

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactionⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structureⁱ

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsⁱ

GO - Molecular functionⁱ

• integrin binding Source: BHF-UCLInferred from physical interactionⁱ
  • "Integrin alpha5beta1 and ADAM-17 interact in vitro and co-localize in migrating HeLa cells."
    Bax D.V., Messent A.J., Tart J., van Hoang M., Kott J., Maciewicz R.A., Humphries M.J.
    J Biol Chem 279:22377-22386(2004) [PubMed] [Europe PMC] [Abstract]
• interleukin-6 receptor binding Source: BHF-UCLInferred from physical interactionⁱ
  • "Bacterial induction of TNF-alpha converting enzyme expression and IL-6 receptor alpha shedding regulates airway inflammatory signaling."
    Gomez M.I., Sokol S.H., Muir A.B., Soong G., Bastien J., Prince A.S.
    J Immunol 175:1930-1936(2005) [PubMed] [Europe PMC] [Abstract]
• Notch binding Source: UniProtKBInferred from direct assayⁱ
  • Ref.15

    "The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality."
    Boskovski M.T., Yuan S., Pedersen N.B., Goth C.K., Makova S., Clausen H., Brueckner M., Khokha M.K.
    Nature 504:456-459(2013) [PubMed] [Europe PMC] [Abstract]

    Cited for: FUNCTION.
• PDZ domain binding Source: BHF-UCLInferred from physical interactionⁱ
  • "Evidence for regulation of the tumor necrosis factor alpha-convertase (TACE) by protein-tyrosine phosphatase PTPH1."
    Zheng Y., Schlondorff J., Blobel C.P.
    J Biol Chem 277:42463-42470(2002) [PubMed] [Europe PMC] [Abstract]
• SH3 domain binding Source: UniProtKB-KW

Protein-protein interaction databases

Chemistry databases

Miscellaneous databases

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structureⁱ

Secondary structure

3D structure databases

Miscellaneous databases

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsⁱ

Domains and Repeats

Region

Motif

Compositional bias

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domainⁱ

Keywords - Domainⁱ

Phylogenomic databases

Family and domain databases

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequences (2+)ⁱ

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusⁱ: Complete.

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is in its mature form or if it represents the precursor.<p><a href='/help/sequence_processing' target='_top'>More...</a></p>Sequence processingⁱ: The displayed sequence is further processed into a mature form.

This entry has 2 described isoforms and 5 potential isoforms that are computationally mapped.Show allAlign All

        10         20         30         40         50
MRQSLLFLTS VVPFVLAPRP PDDPGFGPHQ RLEKLDSLLS DYDILSLSNI 
        60         70         80         90        100
QQHSVRKRDL QTSTHVETLL TFSALKRHFK LYLTSSTERF SQNFKVVVVD 
       110        120        130        140        150
GKNESEYTVK WQDFFTGHVV GEPDSRVLAH IRDDDVIIRI NTDGAEYNIE 
       160        170        180        190        200
PLWRFVNDTK DKRMLVYKSE DIKNVSRLQS PKVCGYLKVD NEELLPKGLV 
       210        220        230        240        250
DREPPEELVH RVKRRADPDP MKNTCKLLVV ADHRFYRYMG RGEESTTTNY 
       260        270        280        290        300
LIELIDRVDD IYRNTSWDNA GFKGYGIQIE QIRILKSPQE VKPGEKHYNM 
       310        320        330        340        350
AKSYPNEEKD AWDVKMLLEQ FSFDIAEEAS KVCLAHLFTY QDFDMGTLGL 
       360        370        380        390        400
AYVGSPRANS HGGVCPKAYY SPVGKKNIYL NSGLTSTKNY GKTILTKEAD 
       410        420        430        440        450
LVTTHELGHN FGAEHDPDGL AECAPNEDQG GKYVMYPIAV SGDHENNKMF 
       460        470        480        490        500
SNCSKQSIYK TIESKAQECF QERSNKVCGN SRVDEGEECD PGIMYLNNDT 
       510        520        530        540        550
CCNSDCTLKE GVQCSDRNSP CCKNCQFETA QKKCQEAINA TCKGVSYCTG 
       560        570        580        590        600
NSSECPPPGN AEDDTVCLDL GKCKDGKCIP FCEREQQLES CACNETDNSC 
       610        620        630        640        650
KVCCRDLSGR CVPYVDAEQK NLFLRKGKPC TVGFCDMNGK CEKRVQDVIE 
       660        670        680        690        700
RFWDFIDQLS INTFGKFLAD NIVGSVLVFS LIFWIPFSIL VHCVDKKLDK 
       710        720        730        740        750
QYESLSLFHP SNVEMLSSMD SASVRIIKPF PAPQTPGRLQ PAPVIPSAPA 
       760        770        780        790        800
APKLDHQRMD TIQEDPSTDS HMDEDGFEKD PFPNSSTAAK SFEDLTDHPV 
       810        820 
TRSEKAASFK LQRQNRVDSK ETEC                             

        10         20         30         40         50
MRQSLLFLTS VVPFVLAPRP PDDPGFGPHQ RLEKLDSLLS DYDILSLSNI 
        60         70         80         90        100
QQHSVRKRDL QTSTHVETLL TFSALKRHFK LYLTSSTERF SQNFKVVVVD 
       110        120        130        140        150
GKNESEYTVK WQDFFTGHVV GEPDSRVLAH IRDDDVIIRI NTDGAEYNIE 
       160        170        180        190        200
PLWRFVNDTK DKRMLVYKSE DIKNVSRLQS PKVCGYLKVD NEELLPKGLV 
       210        220        230        240        250
DREPPEELVH RVKRRADPDP MKNTCKLLVV ADHRFYRYMG RGEESTTTNY 
       260        270        280        290        300
LIELIDRVDD IYRNTSWDNA GFKGYGIQIE QIRILKSPQE VKPGEKHYNM 
       310        320        330        340        350
AKSYPNEEKD AWDVKMLLEQ FSFDIAEEAS KVCLAHLFTY QDFDMGTLGL 
       360        370        380        390        400
AYVGSPRANS HGGVCPKAYY SPVGKKNIYL NSGLTSTKNY GKTILTKEAD 
       410        420        430        440        450
LVTTHELGHN FGAEHDPDGL AECAPNEDQG GKYVMYPIAV SGDHENNKMF 
       460        470        480        490        500
SNCSKQSIYK TIESKAQECF QERSNKVCGN SRVDEGEECD PGIMYLNNDT 
       510        520        530        540        550
CCNSDCTLKE GVQCSDRNSP CCKNCQFETA QKKCQEAINA TCKGVSYCTG 
       560        570        580        590        600
NSSECPPPGN AEDDTVCLDL GKCKDGKCIP FCEREQQLES CACNETDNSC 
       610        620        630        640        650
KVCCRDLSGR CVPYVDAEQK NLFLRKGKPC TVGFCDMNGK CEKRVQDVIE 
       660        670        680        690 
RFWDFIDQLS INTFGKFLAD NIVGSVLVFS LIFWIPFSIL VHCV       

Experimental Info

Natural variant

Alternative sequence

Sequence databases

Genome annotation databases

Keywords - Coding sequence diversityⁱ

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsⁱ

• 100% Identity
• 90% Identity
• 50% Identity

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesⁱ

<p>This subsection of the <a href="http://www.uniprot.org/manual/cross%5Freferences%5Fsection">Cross-references</a> section provides links to various web resources that are relevant for a specific protein.<p><a href='/help/web_resource' target='_top'>More...</a></p>Web resourcesⁱ

Sequence databases

3D structure databases

Protein-protein interaction databases

Chemistry databases

Protein family/group databases

PTM databases

Genetic variation databases

Proteomic databases

Protocols and materials databases

Genome annotation databases