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NameNeutrophil elastase
Synonyms
  • 3.4.21.37
  • Bone marrow serine protease
  • ELA2
  • Elastase-2
  • HLE
  • Human leukocyte elastase
  • Medullasin
  • PMN elastase
Gene NameELANE
OrganismHuman
Amino acid sequence
>lcl|BSEQ0000785|Neutrophil elastase
MTLGRRLACLFLACVLPALLLGGTALASEIVGGRRARPHAWPFMVSLQLRGGHFCGATLI
APNFVMSAAHCVANVNVRAVRVVLGAHNLSRREPTRQVFAVQRIFENGYDPVNLLNDIVI
LQLNGSATINANVQVAQLPAQGRRLGNGVQCLAMGWGLLGRNRGIASVLQELNVTVVTSL
CRRSNVCTLVRGRQAGVCFGDSGSPLVCNGLIHGIASFVRGGCASGLYPDAFAPVAQFVN
WIDSIIQRSEDNPCPHPRDPDPASRTH
Number of residues267
Molecular Weight28517.81
Theoretical pI9.41
GO Classification
Functions
  • protease binding
  • cytokine binding
  • heparin binding
  • RNA polymerase II transcription corepressor activity
  • peptidase activity
  • endopeptidase activity
  • serine-type endopeptidase activity
Processes
  • response to UV
  • positive regulation of MAP kinase activity
  • proteolysis
  • response to yeast
  • positive regulation of smooth muscle cell proliferation
  • phagocytosis
  • collagen catabolic process
  • acute inflammatory response to antigenic stimulus
  • extracellular matrix disassembly
  • negative regulation of chemokine biosynthetic process
  • extracellular matrix organization
  • negative regulation of chemotaxis
  • leukocyte migration
  • negative regulation of growth of symbiont in host
  • defense response to bacterium
  • negative regulation of interleukin-8 biosynthetic process
  • negative regulation of inflammatory response
  • neutrophil mediated killing of fungus
  • response to lipopolysaccharide
  • positive regulation of immune response
  • negative regulation of transcription from RNA polymerase II promoter
  • positive regulation of interleukin-8 biosynthetic process
  • protein catabolic process
  • cellular calcium ion homeostasis
Components
  • extracellular region
  • extracellular space
  • cell surface
  • extracellular exosome
  • transcriptional repressor complex
  • secretory granule
  • cytoplasm
General FunctionSerine-type endopeptidase activity
Specific FunctionModifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID296665
UniProtKB IDP08246
UniProtKB Entry NameELNE_HUMAN
Cellular LocationCytoplasmic
Gene sequence
>lcl|BSEQ0010273|Neutrophil elastase (ELANE)
ATGACCCTCGGCCGCCGACTCGCGTGTCTTTTCCTCGCCTGTGTCCTGCCGGCCTTGCTG
CTGGGGGGCACCGCGCTGGCCTCGGAGATTGTGGGGGGCCGGCGAGCGCGGCCCCACGCG
TGGCCCTTCATGGTGTCCCTGCAGCTGCGCGGAGGCCACTTCTGCGGCGCCACCCTGATT
GCGCCCAACTTCGTCATGTCGGCCGCGCACTGCGTGGCGAATGTAAACGTCCGCGCGGTG
CGGGTGGTCCTGGGAGCCCATAACCTCTCGCGGCGGGAGCCCACCCGGCAGGTGTTCGCC
GTGCAGCGCATCTTCGAAAACGGCTACGACCCCGTAAACTTGCTCAACGACATCGTGATT
CTCCAGCTCAACGGGTCGGCCACCATCAACGCCAACGTGCAGGTGGCCCAGCTGCCGGCT
CAGGGACGCCGCCTGGGCAACGGGGTGCAGTGCCTGGCCATGGGCTGGGGCCTTCTGGGC
AGGAACCGTGGGATCGCCAGCGTCCTGCAGGAGCTCAACGTGACGGTGGTGACGTCCCTC
TGCCGTCGCAGCAACGTCTGCACTCTCGTGAGGGGCCGGCAGGCCGGCGTCTGTTTCGGG
GACTCCGGCAGCCCCTTGGTCTGCAACGGGCTAATCCACGGAATTGCCTCCTTCGTCCGG
GGAGGCTGCGCCTCAGGGCTCTACCCCGATGCCTTTGCCCCGGTGGCACAGTTTGTAAAC
TGGATCGACTCTATCATCCAACGCTCCGAGGACAACCCCTGTCCCCACCCCCGGGACCCG
GACCCGGCCAGCAGGACCCACTGA
GenBank Gene IDY00477
GeneCard IDNot Available
GenAtlas IDELA2
HGNC IDHGNC:3309
Chromosome Location19
Locus19p13.3
References
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  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. 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. 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. 2322278
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  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. 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. 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. 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. 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. 3422232
  11. Farley D, Salvesen G, Travis J: Molecular cloning of human neutrophil elastase. Biol Chem Hoppe Seyler. 1988 May;369 Suppl:3-7. 2462434
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  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. 15140022
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  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. 19159218
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  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. 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. 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. 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. 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. 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. 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. 14962902
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  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. 19036076
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  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. 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. 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. 23463630