true 2001-06-20 2008-07-22 96 ADA17_HUMAN AD17_HUMAN ADAM 17 A disintegrin and metalloproteinase domain 17 TNF-alpha-converting enzyme TNF-alpha convertase Snake venom-like protease CD156b 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. doi:10.1038/385733a0 1997 Nature 385 733-736 NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A) PARTIAL PROTEIN SEQUENCE Leukocyte Monocyte 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. doi:10.1038/385729a0 1997 Nature 385 729-733 NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND B) Patel I.R. Attur M.G. Patel R.N. Stuchin S.A. Abagyan R.A. Abramson S.B. Amin A.R. 1998 J. Immunol. 160 4570-4579 NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A) Cartilage Diaz-Rodriguez E. Montero J.C. Esparis-Ogando A. Yuste L. Pandiella A. doi:10.1091/mbc.01-11-0561 2002 Mol. Biol. Cell 13 2031-2044 PHOSPHORYLATION AT THR-735 Thathiah A. Blobel C.P. Carson D.D. doi:10.1074/jbc.M208326200 2003 J. Biol. Chem. 278 3386-3394 INTERACTION WITH MUC1 FUNCTION Fan H. Turck C.W. Derynck R. doi:10.1074/jbc.M300331200 2003 J. Biol. Chem. 278 18617-18627 PHOSPHORYLATION Olsen J.V. Blagoev B. Gnad F. Macek B. Kumar C. Mortensen P. Mann M. doi:10.1016/j.cell.2006.09.026 2006 Cell 127 635-648 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-379; SER-382 AND SER-791 MASS SPECTROMETRY Epithelium 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. doi:10.1073/pnas.95.7.3408 1998 Proc. Natl. Acad. Sci. U.S.A. 95 3408-3412 X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 219-473 ADAM17 CSVP TACE 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). 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. Binds 1 zinc ion per subunit. Interacts with MAD2L1 and MUC1. 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. In arthritis-affected cartilage. 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). 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. The precursor is cleaved by a furin endopeptidase (By similarity). Phosphorylated. Stimulation by growth factor or phorbol 12-myristate 13-acetate induces phosphorylation of Ser-819 but decreases phosphorylation of Ser-791. Contains 1 disintegrin domain. Contains 1 peptidase M12B domain. 1 17 18 214 ADAM 17 215 824 Extracellular 215 671 672 692 Cytoplasmic 693 824 Peptidase M12B 223 474 Disintegrin 475 563 Crambin-like 603 671 Cysteine switch 182 189 SH3-binding 731 738 SH3-binding 741 748 Poly-Val 96 99 Cys-rich 564 602 406 406 Zinc (in inhibited form) 184 184 Zinc (catalytic) 405 405 Zinc (catalytic) 409 409 Zinc (catalytic) 415 415 Phosphotyrosine 379 379 Phosphoserine 382 382 Phosphothreonine; by MAPK 735 735 Phosphoserine 791 791 Phosphoserine 819 819 N-linked (GlcNAc...) 103 103 N-linked (GlcNAc...) 157 157 N-linked (GlcNAc...) 174 174 N-linked (GlcNAc...) 264 264 N-linked (GlcNAc...) 452 452 N-linked (GlcNAc...) 498 498 N-linked (GlcNAc...) 539 539 N-linked (GlcNAc...) 551 551 N-linked (GlcNAc...) 594 594 225 225 333 333 365 365 469 469 423 423 453 453 534 534 555 555 573 573 582 582 578 578 591 591 593 593 600 600 In isoform B. 695 824 A 109 109 N 563 563 A 801 801 N 818 818 224 231 233 238 244 263 269 271 276 284 309 311 314 324 326 329 332 339 344 346 349 351 362 365 369 371 372 375 376 378 382 389 396 410 422 424 427 429 445 448 452 469 No experimental confirmation available. false 2 MAD2L1 Wikipedia; Tumor necrosis factor alpha-converting enzyme entry EMBL EMBL EMBL EMBL RefSeq UniGene PDB 2.00 A/C/E/I=219-474 PDB 2.28 A/B=215-477 PDB 2.30 A/B=215-477 PDB 1.70 A/B=218-474 PDB 2.10 A/B=216-475 PDB 2.02 A/B=218-475 PDB 1.90 A/B/C/D=212-492 PDB 2.00 A=216-477 PDB 2.00 A=216-474 PDBsum PDBsum PDBsum PDBsum PDBsum PDBsum PDBsum PDBsum PDBsum IntAct MEROPS PhosphoSite Ensembl Homo sapiens GeneID KEGG H-InvDB HGNC ADAM17 HPA MIM gene PharmGKB HOGENOM HOVERGEN Reactome Signaling by EGFR CleanEx GermOnline Homo sapiens InterPro Blood-coag_inhib_Disintegrin InterPro EGF_like_reg_CS InterPro Pept_M10A_M12B InterPro Pept_M_Zn_BS InterPro Peptidase_M12B Pfam Disintegrin 1 Pfam Reprolysin 1 ProDom Disintegrin 1 SMART DISIN 1 PROSITE ADAM_MEPRO 1 PROSITE CYSTEINE_SWITCH true PROSITE DISINTEGRIN_1 true PROSITE DISINTEGRIN_2 1 PROSITE ZINC_PROTEASE 1 ProtInc ProtInc IntAct ProtInc 1997-05-01 1 true 93021 A MRQSLLFLTS VVPFVLAPRP PDDPGFGPHQ RLEKLDSLLS DYDILSLSNI QQHSVRKRDL QTSTHVETLL TFSALKRHFK LYLTSSTERF SQNFKVVVVD GKNESEYTVK WQDFFTGHVV GEPDSRVLAH IRDDDVIIRI NTDGAEYNIE PLWRFVNDTK DKRMLVYKSE DIKNVSRLQS PKVCGYLKVD NEELLPKGLV DREPPEELVH RVKRRADPDP MKNTCKLLVV ADHRFYRYMG RGEESTTTNY LIELIDRVDD IYRNTSWDNA GFKGYGIQIE QIRILKSPQE VKPGEKHYNM AKSYPNEEKD AWDVKMLLEQ FSFDIAEEAS KVCLAHLFTY QDFDMGTLGL AYVGSPRANS HGGVCPKAYY SPVGKKNIYL NSGLTSTKNY GKTILTKEAD LVTTHELGHN FGAEHDPDGL AECAPNEDQG GKYVMYPIAV SGDHENNKMF SNCSKQSIYK TIESKAQECF QERSNKVCGN SRVDEGEECD PGIMYLNNDT CCNSDCTLKE GVQCSDRNSP CCKNCQFETA QKKCQEAINA TCKGVSYCTG NSSECPPPGN AEDDTVCLDL GKCKDGKCIP FCEREQQLES CACNETDNSC KVCCRDLSGR CVPYVDAEQK NLFLRKGKPC TVGFCDMNGK CEKRVQDVIE RFWDFIDQLS INTFGKFLAD NIVGSVLVFS LIFWIPFSIL VHCVDKKLDK QYESLSLFHP SNVEMLSSMD SASVRIIKPF PAPQTPGRLQ PAPVIPSAPA APKLDHQRMD TIQEDPSTDS HMDEDGFEKD PFPNSSTAAK SFEDLTDHPV TRSEKAASFK LQRQNRVDSK ETEC B