Disintegrin and metalloproteinase domain-containing protein 17

Details

Name
Disintegrin and metalloproteinase domain-containing protein 17
Synonyms
  • 3.4.24.86
  • ADAM 17
  • CSVP
  • Snake venom-like protease
  • TACE
  • TNF-alpha convertase
  • TNF-alpha-converting enzyme
Gene Name
ADAM17
Organism
Humans
Amino acid sequence
>lcl|BSEQ0007205|Disintegrin and metalloproteinase domain-containing protein 17
MRQSLLFLTSVVPFVLAPRPPDDPGFGPHQRLEKLDSLLSDYDILSLSNIQQHSVRKRDL
QTSTHVETLLTFSALKRHFKLYLTSSTERFSQNFKVVVVDGKNESEYTVKWQDFFTGHVV
GEPDSRVLAHIRDDDVIIRINTDGAEYNIEPLWRFVNDTKDKRMLVYKSEDIKNVSRLQS
PKVCGYLKVDNEELLPKGLVDREPPEELVHRVKRRADPDPMKNTCKLLVVADHRFYRYMG
RGEESTTTNYLIELIDRVDDIYRNTSWDNAGFKGYGIQIEQIRILKSPQEVKPGEKHYNM
AKSYPNEEKDAWDVKMLLEQFSFDIAEEASKVCLAHLFTYQDFDMGTLGLAYVGSPRANS
HGGVCPKAYYSPVGKKNIYLNSGLTSTKNYGKTILTKEADLVTTHELGHNFGAEHDPDGL
AECAPNEDQGGKYVMYPIAVSGDHENNKMFSNCSKQSIYKTIESKAQECFQERSNKVCGN
SRVDEGEECDPGIMYLNNDTCCNSDCTLKEGVQCSDRNSPCCKNCQFETAQKKCQEAINA
TCKGVSYCTGNSSECPPPGNAEDDTVCLDLGKCKDGKCIPFCEREQQLESCACNETDNSC
KVCCRDLSGRCVPYVDAEQKNLFLRKGKPCTVGFCDMNGKCEKRVQDVIERFWDFIDQLS
INTFGKFLADNIVGSVLVFSLIFWIPFSILVHCVDKKLDKQYESLSLFHPSNVEMLSSMD
SASVRIIKPFPAPQTPGRLQPAPVIPSAPAAPKLDHQRMDTIQEDPSTDSHMDEDGFEKD
PFPNSSTAAKSFEDLTDHPVTRSEKAASFKLQRQNRVDSKETEC
Number of residues
824
Molecular Weight
93020.165
Theoretical pI
5.5
GO Classification
Functions
integrin binding / interleukin-6 receptor binding / metalloendopeptidase activity / metallopeptidase activity / Notch binding / PDZ domain binding / zinc ion binding
Processes
B cell differentiation / cell adhesion / cell adhesion mediated by integrin / cell motility / cell surface receptor signaling pathway / collagen catabolic process / defense response to Gram-positive bacterium / epidermal growth factor receptor signaling pathway / epidermal growth factor-activated receptor transactivation by G-protein coupled receptor signaling pathway / extracellular matrix disassembly / extracellular matrix organization / germinal center formation / JAK-STAT cascade involved in growth hormone signaling pathway / membrane protein ectodomain proteolysis / membrane protein intracellular domain proteolysis / negative regulation of transforming growth factor beta receptor signaling pathway / neurotrophin TRK receptor signaling pathway / neutrophil mediated immunity / Notch receptor processing / Notch signaling pathway / PMA-inducible membrane protein ectodomain proteolysis / positive regulation of cell growth / positive regulation of cell migration / positive regulation of cell proliferation / positive regulation of cellular component movement / positive regulation of chemokine production / positive regulation of cyclin-dependent protein serine/threonine kinase activity involved in G1/S transition of mitotic cell cycle / positive regulation of epidermal growth factor-activated receptor activity / positive regulation of leukocyte chemotaxis / positive regulation of protein phosphorylation / positive regulation of T cell chemotaxis / positive regulation of transforming growth factor beta receptor signaling pathway / proteolysis / regulation of mast cell apoptotic process / response to drug / response to high density lipoprotein particle / response to hypoxia / response to lipopolysaccharide / spleen development / T cell differentiation in thymus / tumor necrosis factor-mediated signaling pathway / wound healing, spreading of epidermal cells
Components
actin cytoskeleton / apical plasma membrane / cell surface / cytoplasm / integral component of plasma membrane / membrane / membrane raft / plasma membrane
General Function
Zinc ion binding
Specific Function
Cleaves the membrane-bound precursor of TNF-alpha to its mature soluble form. Responsible for the proteolytical release of soluble JAM3 from endothelial cells surface. 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. Acts as an activator of Notch pathway by mediating cleavage of Notch, generating the membrane-associated intermediate fragment called Notch extracellular truncation (NEXT). Plays a role in the proteolytic processing of ACE2.
Pfam Domain Function
Transmembrane Regions
672-692
Cellular Location
Membrane
Gene sequence
>lcl|BSEQ0020714|Disintegrin and metalloproteinase domain-containing protein 17 (ADAM17)
ATGAGGCAGTCTCTCCTATTCCTGACCAGCGTGGTTCCTTTCGTGCTGGCGCCGCGACCT
CCGGATGACCCGGGCTTCGGCCCCCACCAGAGACTCGAGAAGCTTGATTCTTTGCTCTCA
GACTACGATATTCTCTCTTTATCTAATATCCAGCAGCATTCGGTAAGAAAAAGAGATCTA
CAGACTTCAACACATGTAGAAACACTACTAACTTTTTCAGCTTTGAAAAGGCATTTTAAA
TTATACCTGACATCAAGTACTGAACGTTTTTCACAAAATTTCAAGGTCGTGGTGGTGGAT
GGTAAAAACGAAAGCGAGTACACTGTAAAATGGCAGGACTTCTTCACTGGACACGTGGTT
GGTGAGCCTGACTCTAGGGTTCTAGCCCACATAAGAGATGATGATGTTATAATCAGAATC
AACACAGATGGGGCCGAATATAACATAGAGCCACTTTGGAGATTTGTTAATGATACCAAA
GACAAAAGAATGTTAGTTTATAAATCTGAAGATATCAAGAATGTTTCACGTTTGCAGTCT
CCAAAAGTGTGTGGTTATTTAAAAGTGGATAATGAAGAGTTGCTCCCAAAAGGGTTAGTA
GACAGAGAACCACCTGAAGAGCTTGTTCATCGAGTGAAAAGAAGAGCTGACCCAGATCCC
ATGAAGAACACGTGTAAATTATTGGTGGTAGCAGATCATCGCTTCTACAGATACATGGGC
AGAGGGGAAGAGAGTACAACTACAAATTACTTAATAGAGCTAATTGACAGAGTTGATGAC
ATCTATCGGAACACTTCATGGGATAATGCAGGTTTTAAAGGCTATGGAATACAGATAGAG
CAGATTCGCATTCTCAAGTCTCCACAAGAGGTAAAACCTGGTGAAAAGCACTACAACATG
GCAAAAAGTTACCCAAATGAAGAAAAGGATGCTTGGGATGTGAAGATGTTGCTAGAGCAA
TTTAGCTTTGATATAGCTGAGGAAGCATCTAAAGTTTGCTTGGCACACCTTTTCACATAC
CAAGATTTTGATATGGGAACTCTTGGATTAGCTTATGTTGGCTCTCCCAGAGCAAACAGC
CATGGAGGTGTTTGTCCAAAGGCTTATTATAGCCCAGTTGGGAAGAAAAATATCTATTTG
AATAGTGGTTTGACGAGCACAAAGAATTATGGTAAAACCATCCTTACAAAGGAAGCTGAC
CTGGTTACAACTCATGAATTGGGACATAATTTTGGAGCAGAACATGATCCGGATGGTCTA
GCAGAATGTGCCCCGAATGAGGACCAGGGAGGGAAATATGTCATGTATCCCATAGCTGTG
AGTGGCGATCACGAGAACAATAAGATGTTTTCAAACTGCAGTAAACAATCAATCTATAAG
ACCATTGAAAGTAAGGCCCAGGAGTGTTTTCAAGAACGCAGCAATAAAGTTTGTGGGAAC
TCGAGGGTGGATGAAGGAGAAGAGTGTGATCCTGGCATCATGTATCTGAACAACGACACC
TGCTGCAACAGCGACTGCACGTTGAAGGAAGGTGTCCAGTGCAGTGACAGGAACAGTCCT
TGCTGTAAAAACTGTCAGTTTGAGACTGCCCAGAAGAAGTGCCAGGAGGCGATTAATGCT
ACTTGCAAAGGCGTGTCCTACTGCACAGGTAATAGCAGTGAGTGCCCGCCTCCAGGAAAT
GCTGAAGATGACACTGTTTGCTTGGATCTTGGCAAGTGTAAGGATGGGAAATGCATCCCT
TTCTGCGAGAGGGAACAGCAGCTGGAGTCCTGTGCATGTAATGAAACTGACAACTCCTGC
AAGGTGTGCTGCAGGGACCTTTCTGGCCGCTGTGTGCCCTATGTCGATGCTGAACAAAAG
AACTTATTTTTGAGGAAAGGAAAGCCCTGTACAGTAGGATTTTGTGACATGAATGGCAAA
TGTGAGAAACGAGTACAGGATGTAATTGAACGATTTTGGGATTTCATTGACCAGCTGAGC
ATCAATACTTTTGGAAAGTTTTTAGCAGACAACATCGTTGGGTCTGTCCTGGTTTTCTCC
TTGATATTTTGGATTCCTTTCAGCATTCTTGTCCATTGTGTGGATAAGAAATTGGATAAA
CAGTATGAATCTCTGTCTCTGTTTCACCCCAGTAACGTCGAAATGCTGAGCAGCATGGAT
TCTGCATCGGTTCGCATTATCAAACCCTTTCCTGCGCCCCAGACTCCAGGCCGCCTGCAG
CCTGCCCCTGTGATCCCTTCGGCGCCAGCAGCTCCAAAACTGGACCACCAGAGAATGGAC
ACCATCCAGGAAGACCCCAGCACAGACTCACATATGGACGAGGATGGGTTTGAGAAGGAC
CCCTTCCCAAATAGCAGCACAGCTGCCAAGTCATTTGAGGATCTCACGGACCATCCGGTC
ACCAGAAGTGAAAAGGCTGCCTCCTTTAAACTGCAGCGTCAGAATCGTGTTGACAGCAAA
GAAACAGAGTGCTAA
Chromosome Location
2
Locus
2p25
External Identifiers
ResourceLink
UniProtKB IDP78536
UniProtKB Entry NameADA17_HUMAN
GenBank Protein ID1857673
GenBank Gene IDU86755
HGNC IDHGNC:195
General References
  1. Moss ML, Jin SL, Milla ME, Bickett DM, Burkhart W, Carter HL, Chen WJ, Clay WC, Didsbury JR, Hassler D, Hoffman CR, Kost TA, Lambert MH, Leesnitzer MA, McCauley P, McGeehan G, Mitchell J, Moyer M, Pahel G, Rocque W, Overton LK, Schoenen F, Seaton T, Su JL, Becherer JD, et al.: Cloning of a disintegrin metalloproteinase that processes precursor tumour-necrosis factor-alpha. Nature. 1997 Feb 20;385(6618):733-6. [PubMed:9034191]
  2. Black RA, Rauch CT, Kozlosky CJ, Peschon JJ, Slack JL, Wolfson MF, Castner BJ, Stocking KL, Reddy P, Srinivasan S, Nelson N, Boiani N, Schooley KA, Gerhart M, Davis R, Fitzner JN, Johnson RS, Paxton RJ, March CJ, Cerretti DP: A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells. Nature. 1997 Feb 20;385(6618):729-33. [PubMed:9034190]
  3. Patel IR, Attur MG, Patel RN, Stuchin SA, Abagyan RA, Abramson SB, Amin AR: 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. 1998 May 1;160(9):4570-9. [PubMed:9574564]
  4. Diaz-Rodriguez E, Montero JC, 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. 2002 Jun;13(6):2031-44. [PubMed:12058067]
  5. Thathiah A, Blobel CP, Carson DD: Tumor necrosis factor-alpha converting enzyme/ADAM 17 mediates MUC1 shedding. J Biol Chem. 2003 Jan 31;278(5):3386-94. Epub 2002 Nov 18. [PubMed:12441351]
  6. Fan H, Turck CW, 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. 2003 May 16;278(20):18617-27. Epub 2003 Mar 5. [PubMed:12621058]
  7. Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M: Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell. 2006 Nov 3;127(3):635-48. [PubMed:17081983]
  8. Dephoure N, Zhou C, Villen J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP: A quantitative atlas of mitotic phosphorylation. Proc Natl Acad Sci U S A. 2008 Aug 5;105(31):10762-7. doi: 10.1073/pnas.0805139105. Epub 2008 Jul 31. [PubMed:18669648]
  9. Rabquer BJ, Amin MA, Teegala N, Shaheen MK, Tsou PS, Ruth JH, Lesch CA, Imhof BA, Koch AE: Junctional adhesion molecule-C is a soluble mediator of angiogenesis. J Immunol. 2010 Aug 1;185(3):1777-85. doi: 10.4049/jimmunol.1000556. Epub 2010 Jun 30. [PubMed:20592283]
  10. Xu P, Derynck R: Direct activation of TACE-mediated ectodomain shedding by p38 MAP kinase regulates EGF receptor-dependent cell proliferation. Mol Cell. 2010 Feb 26;37(4):551-66. doi: 10.1016/j.molcel.2010.01.034. [PubMed:20188673]
  11. Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M: Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis. Sci Signal. 2010 Jan 12;3(104):ra3. doi: 10.1126/scisignal.2000475. [PubMed:20068231]
  12. Blaydon DC, Biancheri P, Di WL, Plagnol V, Cabral RM, Brooke MA, van Heel DA, Ruschendorf F, Toynbee M, Walne A, O'Toole EA, Martin JE, Lindley K, Vulliamy T, Abrams DJ, MacDonald TT, Harper JI, Kelsell DP: Inflammatory skin and bowel disease linked to ADAM17 deletion. N Engl J Med. 2011 Oct 20;365(16):1502-8. doi: 10.1056/NEJMoa1100721. [PubMed:22010916]
  13. Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B: System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation. Sci Signal. 2011 Mar 15;4(164):rs3. doi: 10.1126/scisignal.2001570. [PubMed:21406692]
  14. Boskovski MT, Yuan S, Pedersen NB, Goth CK, Makova S, Clausen H, Brueckner M, Khokha MK: The heterotaxy gene GALNT11 glycosylates Notch to orchestrate cilia type and laterality. Nature. 2013 Dec 19;504(7480):456-9. doi: 10.1038/nature12723. Epub 2013 Nov 13. [PubMed:24226769]
  15. Bian Y, Song C, Cheng K, Dong M, Wang F, Huang J, Sun D, Wang L, Ye M, Zou H: An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome. J Proteomics. 2014 Jan 16;96:253-62. doi: 10.1016/j.jprot.2013.11.014. Epub 2013 Nov 22. [PubMed:24275569]
  16. Heurich A, Hofmann-Winkler H, Gierer S, Liepold T, Jahn O, Pohlmann S: TMPRSS2 and ADAM17 cleave ACE2 differentially and only proteolysis by TMPRSS2 augments entry driven by the severe acute respiratory syndrome coronavirus spike protein. J Virol. 2014 Jan;88(2):1293-307. doi: 10.1128/JVI.02202-13. Epub 2013 Nov 13. [PubMed:24227843]
  17. Maskos K, Fernandez-Catalan C, Huber R, Bourenkov GP, Bartunik H, Ellestad GA, Reddy P, Wolfson MF, Rauch CT, Castner BJ, Davis R, Clarke HR, Petersen M, Fitzner JN, Cerretti DP, March CJ, Paxton RJ, Black RA, Bode W: Crystal structure of the catalytic domain of human tumor necrosis factor-alpha-converting enzyme. Proc Natl Acad Sci U S A. 1998 Mar 31;95(7):3408-12. [PubMed:9520379]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB06943(3S)-1-{[4-(but-2-yn-1-yloxy)phenyl]sulfonyl}pyrrolidine-3-thiolexperimentalunknownDetails
DB070793-{[4-(but-2-yn-1-yloxy)phenyl]sulfonyl}propane-1-thiolexperimentalunknownDetails
DB071214-({4-[(4-AMINOBUT-2-YNYL)OXY]PHENYL}SULFONYL)-N-HYDROXY-2,2-DIMETHYLTHIOMORPHOLINE-3-CARBOXAMIDEexperimentalunknownDetails
DB07145(2R)-N-HYDROXY-2-[(3S)-3-METHYL-3-{4-[(2-METHYLQUINOLIN-4-YL)METHOXY]PHENYL}-2-OXOPYRROLIDIN-1-YL]PROPANAMIDEexperimentalunknownDetails
DB07147methyl (1R,2S)-2-(hydroxycarbamoyl)-1-{4-[(2-methylquinolin-4-yl)methoxy]benzyl}cyclopropanecarboxylateexperimentalunknownDetails
DB07189(1S,3R,6S)-4-oxo-6-{4-[(2-phenylquinolin-4-yl)methoxy]phenyl}-5-azaspiro[2.4]heptane-1-carboxylic acidexperimentalunknownDetails
DB07233N-{[4-(but-2-yn-1-yloxy)phenyl]sulfonyl}-5-methyl-D-tryptophanexperimentalunknownDetails
DB07964(3S)-4-{[4-(BUT-2-YNYLOXY)PHENYL]SULFONYL}-N-HYDROXY-2,2-DIMETHYLTHIOMORPHOLINE-3-CARBOXAMIDEexperimentalunknownDetails