Disintegrin and metalloproteinase domain-containing protein 10

Details

Name
Disintegrin and metalloproteinase domain-containing protein 10
Synonyms
  • 3.4.24.81
  • ADAM 10
  • CDw156
  • KUZ
  • Kuzbanian protein homolog
  • MADM
  • Mammalian disintegrin-metalloprotease
Gene Name
ADAM10
Organism
Humans
Amino acid sequence
>lcl|BSEQ0004722|Disintegrin and metalloproteinase domain-containing protein 10
MVLLRVLILLLSWAAGMGGQYGNPLNKYIRHYEGLSYNVDSLHQKHQRAKRAVSHEDQFL
RLDFHAHGRHFNLRMKRDTSLFSDEFKVETSNKVLDYDTSHIYTGHIYGEEGSFSHGSVI
DGRFEGFIQTRGGTFYVEPAERYIKDRTLPFHSVIYHEDDINYPHKYGPQGGCADHSVFE
RMRKYQMTGVEEVTQIPQEEHAANGPELLRKKRTTSAEKNTCQLYIQTDHLFFKYYGTRE
AVIAQISSHVKAIDTIYQTTDFSGIRNISFMVKRIRINTTADEKDPTNPFRFPNIGVEKF
LELNSEQNHDDYCLAYVFTDRDFDDGVLGLAWVGAPSGSSGGICEKSKLYSDGKKKSLNT
GIITVQNYGSHVPPKVSHITFAHEVGHNFGSPHDSGTECTPGESKNLGQKENGNYIMYAR
ATSGDKLNNNKFSLCSIRNISQVLEKKRNNCFVESGQPICGNGMVEQGEECDCGYSDQCK
DECCFDANQPEGRKCKLKPGKQCSPSQGPCCTAQCAFKSKSEKCRDDSDCAREGICNGFT
ALCPASDPKPNFTDCNRHTQVCINGQCAGSICEKYGLEECTCASSDGKDDKELCHVCCMK
KMDPSTCASTGSVQWSRHFSGRTITLQPGSPCNDFRGYCDVFMRCRLVDADGPLARLKKA
IFSPELYENIAEWIVAHWWAVLLMGIALIMLMAGFIKICSVHTPSSNPKLPPPKPLPGTL
KRRRPPQPIQQPQRQRPRESYQMGHMRR
Number of residues
748
Molecular Weight
84141.515
Theoretical pI
7.81
GO Classification
Functions
endopeptidase activity / integrin binding / metalloendopeptidase activity / metallopeptidase activity / protein homodimerization activity / protein kinase binding / receptor binding / zinc ion binding
Processes
axon guidance / cell-cell signaling / collagen catabolic process / constitutive protein ectodomain proteolysis / ephrin receptor signaling pathway / epidermal growth factor receptor signaling pathway / extracellular matrix disassembly / extracellular matrix organization / in utero embryonic development / integrin-mediated signaling pathway / membrane protein ectodomain proteolysis / monocyte activation / negative regulation of cell adhesion / 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 T cell chemotaxis / protein phosphorylation / response to tumor necrosis factor
Components
cell surface / cytoplasm / extracellular exosome / focal adhesion / Golgi apparatus / Golgi-associated vesicle / integral component of membrane / intracellular membrane-bounded organelle / membrane / nucleus / perinuclear endoplasmic reticulum / plasma membrane / postsynaptic density / tetraspanin-enriched microdomain
General Function
Zinc ion binding
Specific Function
Cleaves the membrane-bound precursor of TNF-alpha at '76-Ala-|-Val-77' 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 heparin-binding epidermal growth-like factor, ephrin-A2 and for constitutive and regulated alpha-secretase cleavage of amyloid precursor protein (APP). Contributes to the normal cleavage of the cellular prion protein. Involved in the cleavage of the adhesion molecule L1 at the cell surface and in released membrane vesicles, suggesting a vesicle-based protease activity. Controls also the proteolytic processing of Notch and mediates lateral inhibition during neurogenesis. Responsible for the FasL ectodomain shedding and for the generation of the remnant ADAM10-processed FasL (FasL APL) transmembrane form. Also cleaves the ectodomain of the integral membrane proteins CORIN and ITM2B. May regulate the EFNA5-EPHA3 signaling.
Pfam Domain Function
Transmembrane Regions
673-693
Cellular Location
Cell membrane
Gene sequence
>lcl|BSEQ0020611|Disintegrin and metalloproteinase domain-containing protein 10 (ADAM10)
ATGGTGTTGCTGAGAGTGTTAATTCTGCTCCTCTCCTGGGCGGCGGGGATGGGAGGTCAG
TATGGGAATCCTTTAAATAAATATATCAGACATTATGAAGGATTATCTTACAATGTGGAT
TCATTACACCAAAAACACCAGCGTGCCAAAAGAGCAGTCTCACATGAAGACCAATTTTTA
CGTCTAGATTTCCATGCCCATGGAAGACATTTCAACCTACGAATGAAGAGGGACACTTCC
CTTTTCAGTGATGAATTTAAAGTAGAAACATCAAATAAAGTACTTGATTATGATACCTCT
CATATTTACACTGGACATATTTATGGTGAAGAAGGAAGTTTTAGCCATGGGTCTGTTATT
GATGGAAGATTTGAAGGATTCATCCAGACTCGTGGTGGCACATTTTATGTTGAGCCAGCA
GAGAGATATATTAAAGACCGAACTCTGCCATTTCACTCTGTCATTTATCATGAAGATGAT
ATTAACTATCCCCATAAATACGGTCCTCAGGGGGGCTGTGCAGATCATTCAGTATTTGAA
AGAATGAGGAAATACCAGATGACTGGTGTAGAGGAAGTAACACAGATACCTCAAGAAGAA
CATGCTGCTAATGGTCCAGAACTTCTGAGGAAAAAACGTACAACTTCAGCTGAAAAAAAT
ACTTGTCAGCTTTATATTCAGACTGATCATTTGTTCTTTAAATATTACGGAACACGAGAA
GCTGTGATTGCCCAGATATCCAGTCATGTTAAAGCGATTGATACAATTTACCAGACCACA
GACTTCTCCGGAATCCGTAACATCAGTTTCATGGTGAAACGCATAAGAATCAATACAACT
GCTGATGAGAAGGACCCTACAAATCCTTTCCGTTTCCCAAATATTGGTGTGGAGAAGTTT
CTGGAATTGAATTCTGAGCAGAATCATGATGACTACTGTTTGGCCTATGTCTTCACAGAC
CGAGATTTTGATGATGGCGTACTTGGTCTGGCTTGGGTTGGAGCACCTTCAGGAAGCTCT
GGAGGAATATGTGAAAAAAGTAAACTCTATTCAGATGGTAAGAAGAAGTCCTTAAACACT
GGAATTATTACTGTTCAGAACTATGGGTCTCATGTACCTCCCAAAGTCTCTCACATTACT
TTTGCTCACGAAGTTGGACATAACTTTGGATCCCCACATGATTCTGGAACAGAGTGCACA
CCAGGAGAATCTAAGAATTTGGGTCAAAAAGAAAATGGCAATTACATCATGTATGCAAGA
GCAACATCTGGGGACAAACTTAACAACAATAAATTCTCACTCTGTAGTATTAGAAATATA
AGCCAAGTTCTTGAGAAGAAGAGAAACAACTGTTTTGTTGAATCTGGCCAACCTATTTGT
GGAAATGGAATGGTAGAACAAGGTGAAGAATGTGATTGTGGCTATAGTGACCAGTGTAAA
GATGAATGCTGCTTCGATGCAAATCAACCAGAGGGAAGAAAATGCAAACTGAAACCTGGG
AAACAGTGCAGTCCAAGTCAAGGTCCTTGTTGTACAGCACAGTGTGCATTCAAGTCAAAG
TCTGAGAAGTGTCGGGATGATTCAGACTGTGCAAGGGAAGGAATATGTAATGGCTTCACA
GCTCTCTGCCCAGCATCTGACCCTAAACCAAACTTCACAGACTGTAATAGGCATACACAA
GTGTGCATTAATGGGCAATGTGCAGGTTCTATCTGTGAGAAATATGGCTTAGAGGAGTGT
ACGTGTGCCAGTTCTGATGGCAAAGATGATAAAGAATTATGCCATGTATGCTGTATGAAG
AAAATGGACCCATCAACTTGTGCCAGTACAGGGTCTGTGCAGTGGAGTAGGCACTTCAGT
GGTCGAACCATCACCCTGCAACCTGGATCCCCTTGCAACGATTTTAGAGGTTACTGTGAT
GTTTTCATGCGGTGCAGATTAGTAGATGCTGATGGTCCTCTAGCTAGGCTTAAAAAAGCA
ATTTTTAGTCCAGAGCTCTATGAAAACATTGCTGAATGGATTGTGGCTCATTGGTGGGCA
GTATTACTTATGGGAATTGCTCTGATCATGCTAATGGCTGGATTTATTAAGATATGCAGT
GTTCATACTCCAAGTAGTAATCCAAAGTTGCCTCCTCCTAAACCACTTCCAGGCACTTTA
AAGAGGAGGAGACCTCCACAGCCCATTCAGCAACCCCAGCGTCAGCGGCCCCGAGAGAGT
TATCAAATGGGACACATGAGACGCTAA
Chromosome Location
15
Locus
15q2|15q22
External Identifiers
ResourceLink
UniProtKB IDO14672
UniProtKB Entry NameADA10_HUMAN
GenBank Gene IDAF009615
GenAtlas IDADAM10
HGNC IDHGNC:188
General References
  1. Rosendahl MS, Ko SC, Long DL, Brewer MT, Rosenzweig B, Hedl E, Anderson L, Pyle SM, Moreland J, Meyers MA, Kohno T, Lyons D, Lichenstein HS: Identification and characterization of a pro-tumor necrosis factor-alpha-processing enzyme from the ADAM family of zinc metalloproteases. J Biol Chem. 1997 Sep 26;272(39):24588-93. [Article]
  2. Howard L, Lu X, Mitchell S, Griffiths S, Glynn P: Molecular cloning of MADM: a catalytically active mammalian disintegrin-metalloprotease expressed in various cell types. Biochem J. 1996 Jul 1;317 ( Pt 1):45-50. [Article]
  3. Zody MC, Garber M, Sharpe T, Young SK, Rowen L, O'Neill K, Whittaker CA, Kamal M, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Kodira CD, Madan A, Qin S, Yang X, Abbasi N, Abouelleil A, Arachchi HM, Baradarani L, Birditt B, Bloom S, Bloom T, Borowsky ML, Burke J, Butler J, Cook A, DeArellano K, DeCaprio D, Dorris L 3rd, Dors M, Eichler EE, Engels R, Fahey J, Fleetwood P, Friedman C, Gearin G, Hall JL, Hensley G, Johnson E, Jones C, Kamat A, Kaur A, Locke DP, Madan A, Munson G, Jaffe DB, Lui A, Macdonald P, Mauceli E, Naylor JW, Nesbitt R, Nicol R, O'Leary SB, Ratcliffe A, Rounsley S, She X, Sneddon KM, Stewart S, Sougnez C, Stone SM, Topham K, Vincent D, Wang S, Zimmer AR, Birren BW, Hood L, Lander ES, Nusbaum C: Analysis of the DNA sequence and duplication history of human chromosome 15. Nature. 2006 Mar 30;440(7084):671-5. [Article]
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  5. McKie N, Edwards T, Dallas DJ, Houghton A, Stringer B, Graham R, Russell G, Croucher PI: Expression of members of a novel membrane linked metalloproteinase family (ADAM) in human articular chondrocytes. Biochem Biophys Res Commun. 1997 Jan 13;230(2):335-9. [Article]
  6. Gutwein P, Mechtersheimer S, Riedle S, Stoeck A, Gast D, Joumaa S, Zentgraf H, Fogel M, Altevogt DP: ADAM10-mediated cleavage of L1 adhesion molecule at the cell surface and in released membrane vesicles. FASEB J. 2003 Feb;17(2):292-4. Epub 2002 Dec 3. [Article]
  7. Vincent B, Paitel E, Saftig P, Frobert Y, Hartmann D, De Strooper B, Grassi J, Lopez-Perez E, Checler F: The disintegrins ADAM10 and TACE contribute to the constitutive and phorbol ester-regulated normal cleavage of the cellular prion protein. J Biol Chem. 2001 Oct 12;276(41):37743-6. Epub 2001 Jul 26. [Article]
  8. Chubinskaya S, Mikhail R, Deutsch A, Tindal MH: ADAM-10 protein is present in human articular cartilage primarily in the membrane-bound form and is upregulated in osteoarthritis and in response to IL-1alpha in bovine nasal cartilage. J Histochem Cytochem. 2001 Sep;49(9):1165-76. [Article]
  9. Lemjabbar H, Basbaum C: Platelet-activating factor receptor and ADAM10 mediate responses to Staphylococcus aureus in epithelial cells. Nat Med. 2002 Jan;8(1):41-6. [Article]
  10. Janes PW, Saha N, Barton WA, Kolev MV, Wimmer-Kleikamp SH, Nievergall E, Blobel CP, Himanen JP, Lackmann M, Nikolov DB: Adam meets Eph: an ADAM substrate recognition module acts as a molecular switch for ephrin cleavage in trans. Cell. 2005 Oct 21;123(2):291-304. [Article]
  11. Lewandrowski U, Moebius J, Walter U, Sickmann A: Elucidation of N-glycosylation sites on human platelet proteins: a glycoproteomic approach. Mol Cell Proteomics. 2006 Feb;5(2):226-33. Epub 2005 Oct 31. [Article]
  12. Kirkin V, Cahuzac N, Guardiola-Serrano F, Huault S, Luckerath K, Friedmann E, Novac N, Wels WS, Martoglio B, Hueber AO, Zornig M: The Fas ligand intracellular domain is released by ADAM10 and SPPL2a cleavage in T-cells. Cell Death Differ. 2007 Sep;14(9):1678-87. Epub 2007 Jun 8. [Article]
  13. Martin L, Fluhrer R, Haass C: Substrate requirements for SPPL2b-dependent regulated intramembrane proteolysis. J Biol Chem. 2009 Feb 27;284(9):5662-70. doi: 10.1074/jbc.M807485200. Epub 2008 Dec 29. [Article]
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  19. Jiang J, Wu S, Wang W, Chen S, Peng J, Zhang X, Wu Q: Ectodomain shedding and autocleavage of the cardiac membrane protease corin. J Biol Chem. 2011 Mar 25;286(12):10066-72. doi: 10.1074/jbc.M110.185082. Epub 2011 Feb 2. [Article]
  20. 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. [Article]
  21. Tagliabracci VS, Wiley SE, Guo X, Kinch LN, Durrant E, Wen J, Xiao J, Cui J, Nguyen KB, Engel JL, Coon JJ, Grishin N, Pinna LA, Pagliarini DJ, Dixon JE: A Single Kinase Generates the Majority of the Secreted Phosphoproteome. Cell. 2015 Jun 18;161(7):1619-32. doi: 10.1016/j.cell.2015.05.028. [Article]
  22. Vaca Jacome AS, Rabilloud T, Schaeffer-Reiss C, Rompais M, Ayoub D, Lane L, Bairoch A, Van Dorsselaer A, Carapito C: N-terminome analysis of the human mitochondrial proteome. Proteomics. 2015 Jul;15(14):2519-24. doi: 10.1002/pmic.201400617. Epub 2015 Jun 8. [Article]
  23. Kim M, Suh J, Romano D, Truong MH, Mullin K, Hooli B, Norton D, Tesco G, Elliott K, Wagner SL, Moir RD, Becker KD, Tanzi RE: Potential late-onset Alzheimer's disease-associated mutations in the ADAM10 gene attenuate {alpha}-secretase activity. Hum Mol Genet. 2009 Oct 15;18(20):3987-96. doi: 10.1093/hmg/ddp323. Epub 2009 Jul 15. [Article]
  24. Wei X, Moncada-Pazos A, Cal S, Soria-Valles C, Gartner J, Rudloff U, Lin JC, Rosenberg SA, Lopez-Otin C, Samuels Y: Analysis of the disintegrin-metalloproteinases family reveals ADAM29 and ADAM7 are often mutated in melanoma. Hum Mutat. 2011 Jun;32(6):E2148-75. doi: 10.1002/humu.21477. Epub 2011 Feb 24. [Article]
  25. Kono M, Sugiura K, Suganuma M, Hayashi M, Takama H, Suzuki T, Matsunaga K, Tomita Y, Akiyama M: Whole-exome sequencing identifies ADAM10 mutations as a cause of reticulate acropigmentation of Kitamura, a clinical entity distinct from Dowling-Degos disease. Hum Mol Genet. 2013 Sep 1;22(17):3524-33. doi: 10.1093/hmg/ddt207. Epub 2013 May 10. [Article]
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Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB04991XL784investigationalunknownDetails