[1]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), AND PARTIAL PROTEIN SEQUENCE.
TISSUE=Leukocyte, and Monocyte;
DOI=10.1038/385733a0; PubMed=9034191 [NCBI, ExPASy, EBI, Israel, Japan]
Moss M.L.,
Jin S.-L.C.,
Milla M.E.,
Burkhart W.,
Carter H.L.,
Chen W.-J.,
Clay W.C.,
Didsbury J.R.,
Hassler D.,
Hoffman C.R.,
Kost T.A.,
Lambert M.H.,
Leesnitzer M.A.,
McCauley P.,
McGeehan G.,
Mitchell J.,
Moyer M.,
Pahel G.,
Rocque W., ![]()
Overton L.K.,
Schoenen F.,
Seaton T.,
Su J.-L.,
Warner J.,
Willard D.,
Becherer J.D.;
"Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha.";
Nature 385:733-736(1997).
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[2]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B).
DOI=10.1038/385729a0; PubMed=9034190 [NCBI, ExPASy, EBI, Israel, Japan]
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.;
"A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells.";
Nature 385:729-733(1997).
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[3]
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NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A).
TISSUE=Cartilage;
PubMed=9574564 [NCBI, ExPASy, EBI, Israel, Japan]
Patel I.R.,
Attur M.G.,
Patel R.N.,
Stuchin S.A.,
Abagyan R.A.,
Abramson S.B.,
Amin A.R.;
"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.";
J. Immunol. 160:4570-4579(1998).
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[4]
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PHOSPHORYLATION AT THR-735.
DOI=10.1091/mbc.01-11-0561; PubMed=12058067 [NCBI, ExPASy, EBI, Israel, Japan]
Diaz-Rodriguez E.,
Montero J.C.,
Esparis-Ogando A.,
Yuste L.,
Pandiella A.;
"Extracellular signal-regulated kinase phosphorylates tumor necrosis factor alpha-converting enzyme at threonine 735: a potential role in regulated shedding.";
Mol. Biol. Cell 13:2031-2044(2002).
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[5]
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INTERACTION WITH MUC1, AND FUNCTION.
DOI=10.1074/jbc.M208326200; PubMed=12441351 [NCBI, ExPASy, EBI, Israel, Japan]
Thathiah A.,
Blobel C.P.,
Carson D.D.;
"Tumor necrosis factor-alpha converting enzyme/ADAM 17 mediates MUC1 shedding.";
J. Biol. Chem. 278:3386-3394(2003).
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[6]
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PHOSPHORYLATION.
DOI=10.1074/jbc.M300331200; PubMed=12621058 [NCBI, ExPASy, EBI, Israel, Japan]
Fan H.,
Turck C.W.,
Derynck R.;
"Characterization of growth factor-induced serine phosphorylation of tumor necrosis factor-alpha converting enzyme and of an alternatively translated polypeptide.";
J. Biol. Chem. 278:18617-18627(2003).
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[7]
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PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-379; SER-382 AND SER-791, AND MASS SPECTROMETRY.
TISSUE=Epithelium;
DOI=10.1016/j.cell.2006.09.026; PubMed=17081983 [NCBI, ExPASy, EBI, Israel, Japan]
Olsen J.V.,
Blagoev B.,
Gnad F.,
Macek B.,
Kumar C.,
Mortensen P.,
Mann M.;
"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks.";
Cell 127:635-648(2006).
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[8]
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X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 219-473.
DOI=10.1073/pnas.95.7.3408; PubMed=9520379 [NCBI, ExPASy, EBI, Israel, Japan]
Maskos K.,
Fernandez-Catalan C.,
Huber R.,
Bourenkov G.P.,
Bartunik H.,
Ellestad G.A.,
Reddy P.,
Wolfson M.F.,
Rauch C.T.,
Castner B.J.,
Davis R.,
Clarke H.R.G.,
Petersen M.,
Fitzner J.N.,
Cerretti D.P.,
March C.J.,
Paxton R.J.,
Black R.A.,
Bode W.;
"Crystal structure of the catalytic domain of human tumor necrosis factor-alpha-converting enzyme.";
Proc. Natl. Acad. Sci. U.S.A. 95:3408-3412(1998).
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- FUNCTION: Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. Responsible for the proteolytic release of several other cell-surface proteins, including p75 TNF-receptor, interleukin 1 receptor type II, p55 TNF-receptor, transforming growth factor-alpha, L-selectin, growth hormone receptor, MUC1 and the amyloid precursor protein. Also involved in the activation of Notch pathway (By similarity).
- CATALYTIC ACTIVITY: 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.
- COFACTOR: Binds 1 zinc ion per subunit.
- SUBUNIT: Interacts with MAD2L1 and MUC1.
- INTERACTION:
Q13257:MAD2L1; NbExp=2; IntAct=EBI-78188, EBI-78203;
- SUBCELLULAR LOCATION: Membrane; Single-pass type I membrane protein.
- ALTERNATIVE PRODUCTS:
2 named isoforms [FASTA] produced by alternative splicing.
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| Name | B |
| Isoform ID | P78536-2 |
| Note: No experimental confirmation available. |
| Features which should be applied to build the isoform sequence: VSP_005478. |
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- TISSUE SPECIFICITY: Ubiquitously expressed. Expressed at highest levels in adult heart, placenta, skeletal muscle, pancreas, spleen, thymus, prostate, testes, ovary and small intestine, and in fetal brain, lung, liver and kidney.
- INDUCTION: In arthritis-affected cartilage.
- DOMAIN: Must be membrane anchored to cleave the different substrates. The cytoplasmic domain is not required for the this activity. Only the catalytic domain is essential to shed TNF and p75 TNFR (By similarity).
- DOMAIN: The conserved cysteine present in the cysteine-switch motif binds the catalytic zinc ion, thus inhibiting the enzyme. The dissociation of the cysteine from the zinc ion upon the activation-peptide release activates the enzyme.
- PTM: The precursor is cleaved by a furin endopeptidase (By similarity).
- PTM: Phosphorylated. Stimulation by growth factor or phorbol 12-myristate 13-acetate induces phosphorylation of Ser-819 but decreases phosphorylation of Ser-791.
- SIMILARITY: Contains 1 disintegrin domain.
- SIMILARITY: Contains 1 peptidase M12B domain [view classification].
- WEB RESOURCE: Name=Wikipedia; Note=Tumor necrosis factor alpha-converting enzyme entry; URL="http://en.wikipedia.org/wiki/Tumor_Necrosis_Factor_Alpha_Converting_Enzyme";.
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