Neutrophil elastase

Details

Name
Neutrophil elastase
Synonyms
  • 3.4.21.37
  • Bone marrow serine protease
  • ELA2
  • Elastase-2
  • HLE
  • Human leukocyte elastase
  • Medullasin
  • PMN elastase
Gene Name
ELANE
Organism
Humans
Amino acid sequence
>lcl|BSEQ0000785|Neutrophil elastase
MTLGRRLACLFLACVLPALLLGGTALASEIVGGRRARPHAWPFMVSLQLRGGHFCGATLI
APNFVMSAAHCVANVNVRAVRVVLGAHNLSRREPTRQVFAVQRIFENGYDPVNLLNDIVI
LQLNGSATINANVQVAQLPAQGRRLGNGVQCLAMGWGLLGRNRGIASVLQELNVTVVTSL
CRRSNVCTLVRGRQAGVCFGDSGSPLVCNGLIHGIASFVRGGCASGLYPDAFAPVAQFVN
WIDSIIQRSEDNPCPHPRDPDPASRTH
Number of residues
267
Molecular Weight
28517.81
Theoretical pI
9.41
GO Classification
Functions
cytokine binding / endopeptidase activity / heparin binding / peptidase activity / protease binding / RNA polymerase II transcription corepressor activity / serine-type endopeptidase activity
Processes
acute inflammatory response to antigenic stimulus / cellular calcium ion homeostasis / collagen catabolic process / defense response to bacterium / extracellular matrix disassembly / extracellular matrix organization / leukocyte migration / negative regulation of chemokine biosynthetic process / negative regulation of chemotaxis / negative regulation of growth of symbiont in host / negative regulation of inflammatory response / negative regulation of interleukin-8 biosynthetic process / negative regulation of transcription from RNA polymerase II promoter / neutrophil mediated killing of fungus / phagocytosis / positive regulation of immune response / positive regulation of interleukin-8 biosynthetic process / positive regulation of MAP kinase activity / positive regulation of smooth muscle cell proliferation / protein catabolic process / proteolysis / response to lipopolysaccharide / response to UV / response to yeast
Components
cell surface / cytoplasm / extracellular exosome / extracellular region / extracellular space / secretory granule / transcriptional repressor complex
General Function
Serine-type endopeptidase activity
Specific Function
Modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis.
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Cytoplasmic
Gene sequence
>lcl|BSEQ0010273|Neutrophil elastase (ELANE)
ATGACCCTCGGCCGCCGACTCGCGTGTCTTTTCCTCGCCTGTGTCCTGCCGGCCTTGCTG
CTGGGGGGCACCGCGCTGGCCTCGGAGATTGTGGGGGGCCGGCGAGCGCGGCCCCACGCG
TGGCCCTTCATGGTGTCCCTGCAGCTGCGCGGAGGCCACTTCTGCGGCGCCACCCTGATT
GCGCCCAACTTCGTCATGTCGGCCGCGCACTGCGTGGCGAATGTAAACGTCCGCGCGGTG
CGGGTGGTCCTGGGAGCCCATAACCTCTCGCGGCGGGAGCCCACCCGGCAGGTGTTCGCC
GTGCAGCGCATCTTCGAAAACGGCTACGACCCCGTAAACTTGCTCAACGACATCGTGATT
CTCCAGCTCAACGGGTCGGCCACCATCAACGCCAACGTGCAGGTGGCCCAGCTGCCGGCT
CAGGGACGCCGCCTGGGCAACGGGGTGCAGTGCCTGGCCATGGGCTGGGGCCTTCTGGGC
AGGAACCGTGGGATCGCCAGCGTCCTGCAGGAGCTCAACGTGACGGTGGTGACGTCCCTC
TGCCGTCGCAGCAACGTCTGCACTCTCGTGAGGGGCCGGCAGGCCGGCGTCTGTTTCGGG
GACTCCGGCAGCCCCTTGGTCTGCAACGGGCTAATCCACGGAATTGCCTCCTTCGTCCGG
GGAGGCTGCGCCTCAGGGCTCTACCCCGATGCCTTTGCCCCGGTGGCACAGTTTGTAAAC
TGGATCGACTCTATCATCCAACGCTCCGAGGACAACCCCTGTCCCCACCCCCGGGACCCG
GACCCGGCCAGCAGGACCCACTGA
Chromosome Location
19
Locus
19p13.3
External Identifiers
ResourceLink
UniProtKB IDP08246
UniProtKB Entry NameELNE_HUMAN
GenBank Protein ID296665
GenBank Gene IDY00477
GenAtlas IDELA2
HGNC IDHGNC:3309
General References
  1. Nakamura H, Okano K, Aoki Y, Shimizu H, Naruto M: Nucleotide sequence of human bone marrow serine protease (medullasin) gene. Nucleic Acids Res. 1987 Nov 25;15(22):9601-2. [PubMed:3479752]
  2. Takahashi H, Nukiwa T, Yoshimura K, Quick CD, States DJ, Holmes MD, Whang-Peng J, Knutsen T, Crystal RG: Structure of the human neutrophil elastase gene. J Biol Chem. 1988 Oct 15;263(29):14739-47. [PubMed:2902087]
  3. Farley D, Travis J, Salvesen G: The human neutrophil elastase gene. Analysis of the nucleotide sequence reveals three distinct classes of repetitive DNA. Biol Chem Hoppe Seyler. 1989 Jul;370(7):737-44. [PubMed:2775493]
  4. Okano K, Aoki Y, Shimizu H, Naruto M: Functional expression of human leukocyte elastase (HLE)/medullasin in eukaryotic cells. Biochem Biophys Res Commun. 1990 Mar 30;167(3):1326-32. [PubMed:2322278]
  5. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334]
  6. Okano K, Aoki Y, Sakurai T, Kajitani M, Kanai S, Shimazu T, Shimizu H, Naruto M: Molecular cloning of complementary DNA for human medullasin: an inflammatory serine protease in bone marrow cells. J Biochem. 1987 Jul;102(1):13-6. [PubMed:2822677]
  7. Sinha S, Watorek W, Karr S, Giles J, Bode W, Travis J: Primary structure of human neutrophil elastase. Proc Natl Acad Sci U S A. 1987 Apr;84(8):2228-32. [PubMed:3550808]
  8. Gabay JE, Scott RW, Campanelli D, Griffith J, Wilde C, Marra MN, Seeger M, Nathan CF: Antibiotic proteins of human polymorphonuclear leukocytes. Proc Natl Acad Sci U S A. 1989 Jul;86(14):5610-4. [PubMed:2501794]
  9. Gaskin G, Kendal H, Coulthart A, Turner N, Pusey CD: Use of proteinase 3 purified by reverse phase HPLC to detect autoantibodies in systemic vasculitis. J Immunol Methods. 1995 Mar 13;180(1):25-33. [PubMed:7897245]
  10. Takahashi H, Nukiwa T, Basset P, Crystal RG: Myelomonocytic cell lineage expression of the neutrophil elastase gene. J Biol Chem. 1988 Feb 15;263(5):2543-7. [PubMed:3422232]
  11. Farley D, Salvesen G, Travis J: Molecular cloning of human neutrophil elastase. Biol Chem Hoppe Seyler. 1988 May;369 Suppl:3-7. [PubMed:2462434]
  12. Aoki Y, Hase T: The primary structure and elastinolytic activity of medullasin (a serine protease of bone marrow). Biochem Biophys Res Commun. 1991 Jul 31;178(2):501-6. [PubMed:1859409]
  13. Tralau T, Meyer-Hoffert U, Schroder JM, Wiedow O: Human leukocyte elastase and cathepsin G are specific inhibitors of C5a-dependent neutrophil enzyme release and chemotaxis. Exp Dermatol. 2004 May;13(5):316-25. [PubMed:15140022]
  14. Duan Z, Li FQ, Wechsler J, Meade-White K, Williams K, Benson KF, Horwitz M: A novel notch protein, N2N, targeted by neutrophil elastase and implicated in hereditary neutropenia. Mol Cell Biol. 2004 Jan;24(1):58-70. [PubMed:14673143]
  15. Chen R, Jiang X, Sun D, Han G, Wang F, Ye M, Wang L, Zou H: Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry. J Proteome Res. 2009 Feb;8(2):651-61. doi: 10.1021/pr8008012. [PubMed:19159218]
  16. Burkard TR, Planyavsky M, Kaupe I, Breitwieser FP, Burckstummer T, Bennett KL, Superti-Furga G, Colinge J: Initial characterization of the human central proteome. BMC Syst Biol. 2011 Jan 26;5:17. doi: 10.1186/1752-0509-5-17. [PubMed:21269460]
  17. 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. [PubMed:25944712]
  18. Navia MA, McKeever BM, Springer JP, Lin TY, Williams HR, Fluder EM, Dorn CP, Hoogsteen K: Structure of human neutrophil elastase in complex with a peptide chloromethyl ketone inhibitor at 1.84-A resolution. Proc Natl Acad Sci U S A. 1989 Jan;86(1):7-11. [PubMed:2911584]
  19. Wei AZ, Mayr I, Bode W: The refined 2.3 A crystal structure of human leukocyte elastase in a complex with a valine chloromethyl ketone inhibitor. FEBS Lett. 1988 Jul 18;234(2):367-73. [PubMed:3391280]
  20. Bode W, Wei AZ, Huber R, Meyer E, Travis J, Neumann S: X-ray crystal structure of the complex of human leukocyte elastase (PMN elastase) and the third domain of the turkey ovomucoid inhibitor. EMBO J. 1986 Oct;5(10):2453-8. [PubMed:3640709]
  21. Horwitz M, Benson KF, Person RE, Aprikyan AG, Dale DC: Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis. Nat Genet. 1999 Dec;23(4):433-6. [PubMed:10581030]
  22. Dale DC, Person RE, Bolyard AA, Aprikyan AG, Bos C, Bonilla MA, Boxer LA, Kannourakis G, Zeidler C, Welte K, Benson KF, Horwitz M: Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia. Blood. 2000 Oct 1;96(7):2317-22. [PubMed:11001877]
  23. Ancliff PJ, Gale RE, Liesner R, Hann IM, Linch DC: Mutations in the ELA2 gene encoding neutrophil elastase are present in most patients with sporadic severe congenital neutropenia but only in some patients with the familial form of the disease. Blood. 2001 Nov 1;98(9):2645-50. [PubMed:11675333]
  24. Ancliff PJ, Gale RE, Watts MJ, Liesner R, Hann IM, Strobel S, Linch DC: Paternal mosaicism proves the pathogenic nature of mutations in neutrophil elastase in severe congenital neutropenia. Blood. 2002 Jul 15;100(2):707-9. [PubMed:12091371]
  25. Bellanne-Chantelot C, Clauin S, Leblanc T, Cassinat B, Rodrigues-Lima F, Beaufils S, Vaury C, Barkaoui M, Fenneteau O, Maier-Redelsperger M, Chomienne C, Donadieu J: Mutations in the ELA2 gene correlate with more severe expression of neutropenia: a study of 81 patients from the French Neutropenia Register. Blood. 2004 Jun 1;103(11):4119-25. Epub 2004 Feb 12. [PubMed:14962902]
  26. Salipante SJ, Benson KF, Luty J, Hadavi V, Kariminejad R, Kariminejad MH, Rezaei N, Horwitz MS: Double de novo mutations of ELA2 in cyclic and severe congenital neutropenia. Hum Mutat. 2007 Sep;28(9):874-81. [PubMed:17436313]
  27. Lee ST, Yoon HS, Kim HJ, Lee JH, Park JH, Kim SH, Seo JJ, Im HJ: A novel mutation Ala57Val of the ELA2 gene in a Korean boy with severe congenital neutropenia. Ann Hematol. 2009 Jun;88(6):593-5. doi: 10.1007/s00277-008-0629-y. Epub 2008 Oct 23. [PubMed:18946670]
  28. Smith BN, Ancliff PJ, Pizzey A, Khwaja A, Linch DC, Gale RE: Homozygous HAX1 mutations in severe congenital neutropenia patients with sporadic disease: a novel mutation in two unrelated British kindreds. Br J Haematol. 2009 Mar;144(5):762-70. doi: 10.1111/j.1365-2141.2008.07493.x. Epub 2008 Nov 22. [PubMed:19036076]
  29. Shiohara M, Shigemura T, Saito S, Tanaka M, Yanagisawa R, Sakashita K, Asada H, Ishii E, Koike K, Chin M, Kobayashi M, Koike K: Ela2 mutations and clinical manifestations in familial congenital neutropenia. J Pediatr Hematol Oncol. 2009 May;31(5):319-24. doi: 10.1097/MPH.0b013e3181984dbe. [PubMed:19415009]
  30. Germeshausen M, Zeidler C, Stuhrmann M, Lanciotti M, Ballmaier M, Welte K: Digenic mutations in severe congenital neutropenia. Haematologica. 2010 Jul;95(7):1207-10. doi: 10.3324/haematol.2009.017665. Epub 2010 Mar 10. [PubMed:20220065]
  31. Fioredda F, Calvillo M, Lanciotti M, Lanza T, Giunti L, Castagnola E, Lorenzi I, Tonelli R, Ghezzi P, Dufour C: Pegfilgrastim in children with severe congenital neutropenia. Pediatr Blood Cancer. 2010 Mar;54(3):465-7. doi: 10.1002/pbc.22350. [PubMed:19927291]
  32. van de Vosse E, Verhard EM, Tool AJ, de Visser AW, Kuijpers TW, Hiemstra PS, van Dissel JT: Severe congenital neutropenia in a multigenerational family with a novel neutrophil elastase (ELANE) mutation. Ann Hematol. 2011 Feb;90(2):151-8. doi: 10.1007/s00277-010-1056-4. Epub 2010 Aug 28. [PubMed:20803142]
  33. Kurnikova M, Maschan M, Dinova E, Shagina I, Finogenova N, Mamedova E, Polovtseva T, Shagin D, Shcherbina A: Four novel ELANE mutations in patients with congenital neutropenia. Pediatr Blood Cancer. 2011 Aug;57(2):332-5. doi: 10.1002/pbc.23104. Epub 2011 Mar 21. [PubMed:21425445]
  34. Germeshausen M, Deerberg S, Peter Y, Reimer C, Kratz CP, Ballmaier M: The spectrum of ELANE mutations and their implications in severe congenital and cyclic neutropenia. Hum Mutat. 2013 Jun;34(6):905-14. doi: 10.1002/humu.22308. Epub 2013 Apr 2. [PubMed:23463630]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB02341Mdl 101,146experimentalunknownDetails
DB00019PegfilgrastimapprovedunknownDetails
DB00099Filgrastimapprovedunknownother/unknownDetails
DB03925Freselestatexperimental, investigationalunknowninhibitorDetails
DB00058Alpha-1-proteinase inhibitorapprovedyesinhibitorDetails
DB05161ElafininvestigationalunknownDetails