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| Neutrofiilielastaasi |
| Päivitän tätä artikkelia 2.4. 2020, koska tämä mainitaan SARS-viruksen yhteydessä ja mm. se hajoittaa alfa1-antitrypsiiniä keuhkosta. Tämä asia huomattiin jo 2004 edellisen SARS- epidemian jälkeen, koska ilmeni alfa1-antitrypsiinin lyhentynyttä muotoa, joka ei ollut niin tehokasta keuhkoissa kuin normaali antitrypsiini. Tupakanpoltto vielä pahensi tilannetta.https://www.researchgate.net/publication
Alla on valaiseva kuva elastaasin osuudesta myeloproliferatiivisea taudisa.
/23957215_Leukocytosis_JAK2V617F_
Mutation_and_Hemostasis_in_Myeloproliferative_Disorders |
Suomennosta:
Seriiniproteaasi neutrofiilielastaasi (NE) on samaa perhettä kuin kymotrypsiini ja sillä on laaja substraattispesifisyys.
Tämä on toinen ihmisen kahdesta elastaasimuodosta.
Neutrofiilien elastaasi on rakenteeltaan 218 aminohapon peptidi ja siinä onn kaksi aspartaatti-linkkiytynyttä hiilihydraattiketjua ( glykosylaatio). Se esiintyy azurofiilisissä jyväsissä neutrofiilin solulimassa Näyttää olevan kaksi muotoa neutrofiilien elastaaasi
, IIa, IIb
Elastaasia erittää sekä neutrofiilit että makrofagit tulehduksen aikana. Se tuhoaa sekä bakteereita että isäntäkudosta
Preproproteiinissa on 267 a.a.
Kuten muutkin
seriiniproteaasit niissä on sofistinen varauksellinen relekohta järjestelmä (Charge relay system!) jossa on katalyyttinen kolmikko 70His, 117Asp ja 202Ser., joita on sirotettuna polypeptidin primäärisekvenssiin, mutta joka kokoontuu yhteen 3D- konformaatioon proteiinin laskostuessa . Koodaava geeni ELA2 omaa 5 exonia.
- Neutrophil elastase , (EC 3.4.21.37,
leukocyte elastase, ELANE, ELA2,
elastase 2, neutrophil, elaszym, serine elastase) is
a serine proteinase in the same family as
chymotrypsin and has broad substrate specificity.
Secreted by neutrophils and macrophages during inflammation, it destroys bacteria and host tissue.[1]
As with other serine proteinases it contains a
charge relay system composed of the
catalytic triad of
histidine, aspartate, and serine residues that are dispersed throughout
the primary sequence of the polypeptide but that are brought together
in the three dimensional conformation of the folded protein. The gene
encoding neutrophil elastase, ELA2, consists of five exons.
LOCUS NP_001963 267 aa linear PRI 03-FEB-2020
DEFINITION neutrophil elastase preproprotein [Homo sapiens].
ACCESSION NP_001963
VERSION NP_001963.1
DBSOURCE REFSEQ: accession NM_001972.4
KEYWORDS RefSeq; MANE Select.
SOURCE Homo sapiens (human)
ORGANISM Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
REFERENCE 1 (residues 1 to 267)
AUTHORS Yu L, Zhong L, Xiong L, Dan W, Li J, Ye J, Wan P, Luo X, Chu X, Liu
C, He C, Mu F and Liu B.
TITLE Neutrophil elastase-mediated proteolysis of the tumor suppressor
p200 CUX1 promotes cell proliferation and inhibits cell
differentiation in APL
JOURNAL Life Sci. 242, 117229 (2020)
PUBMED 31887298
REMARK GeneRIF: mediates proteolysis of the tumor suppressor p200 CUX1,
which promotes cell proliferation and inhibits cell differentiation
in acute promyelocytic leukemia
REFERENCE 2 (residues 1 to 267)
AUTHORS Thulborn SJ, Mistry V, Brightling CE, Moffitt KL, Ribeiro D and
Bafadhel M.
TITLE Neutrophil elastase as a biomarker for bacterial infection in COPD
JOURNAL Respir. Res. 20 (1), 170 (2019)
PUBMED 31362723
REMARK GeneRIF: Neutrophil elastase is elevated in the sputum during
exacerbations of chronic obstructive pulmonary disease.
Publication Status: Online-Only
REFERENCE 3 (residues 1 to 267)
AUTHORS Shigemura T, Kobayashi N, Agematsu K, Ohara O and Nakazawa Y.
TITLE Mosaicism of an ELANE Mutation in an Asymptomatic Mother
JOURNAL J. Clin. Immunol. 39 (1), 106-111 (2019)
PUBMED 30635825
REMARK GeneRIF: Established the ELANE-mutated and non-mutated iPSCs.
REFERENCE 4 (residues 1 to 267)
AUTHORS Gordon MH, Chauvin A, Boisvert FM and MacNaughton WK.
TITLE Proteolytic Processing of the Epithelial Adherens Junction Molecule
E-Cadherin by Neutrophil Elastase Generates Short Peptides With
Novel Wound-Healing Bioactivity
JOURNAL Cell Mol Gastroenterol Hepatol 7 (2), 483-486 (2019)
PUBMED 30827416
REMARK GeneRIF: the ability of an inflammatory protease, neutrophil
elastase, to process the adherens junction protein E-cadherin to
generate short peptide fragments with effects on epithelial
function, is reported.
REFERENCE 5 (residues 1 to 267)
AUTHORS Horwitz MS, Corey SJ, Grimes HL and Tidwell T.
TITLE ELANE mutations in cyclic and severe congenital neutropenia:
genetics and pathophysiology
JOURNAL Hematol. Oncol. Clin. North Am. 27 (1), 19-41 (2013)
PUBMED 23351986
REMARK GeneRIF: A review discusses how ELANE mutations provide clues into
the pathogenesis of cyclic and severe congenital neutropenia.
Review article
REFERENCE 6 (residues 1 to 267)
AUTHORS Dale,D.C. and Makaryan,V.
TITLE ELANE-Related Neutropenia
JOURNAL (in) Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens
K and Amemiya A (Eds.);
GENEREVIEWS((R));
(1993)
PUBMED 20301705
REFERENCE 7 (residues 1 to 267)
AUTHORS Zimmer M, Medcalf RL, Fink TM, Mattmann C, Lichter P and Jenne DE.
TITLE Three human elastase-like genes coordinately expressed in the
myelomonocyte lineage are organized as a single genetic locus on
19pter
JOURNAL Proc. Natl. Acad. Sci. U.S.A. 89 (17), 8215-8219 (1992)
PUBMED 1518849
REFERENCE 8 (residues 1 to 267)
AUTHORS Higuchi DA, Wun TC, Likert KM and Broze GJ Jr.
TITLE The effect of leukocyte elastase on tissue factor pathway inhibitor
JOURNAL Blood 79 (7), 1712-1719 (1992)
PUBMED 1558967
REFERENCE 9 (residues 1 to 267)
AUTHORS Aoki Y and Hase T.
TITLE The primary structure and elastinolytic activity of medullasin (a
serine protease of bone marrow)
JOURNAL Biochem. Biophys. Res. Commun. 178 (2), 501-506 (1991)
PUBMED 1859409
REFERENCE 10 (residues 1 to 267)
AUTHORS Fletcher TS, Shen WF and Largman C.
TITLE Primary structure of human pancreatic elastase 2 determined by
sequence analysis of the cloned mRNA
JOURNAL Biochemistry 26 (23), 7256-7261 (1987)
PUBMED 3427074
COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff. The
reference sequence was derived from M34379.1 and BI254663.1.
Summary: Elastases form a subfamily of serine proteases that
hydrolyze many proteins in addition to elastin. Humans have six
elastase genes which encode structurally similar proteins. The
encoded preproprotein is proteolytically processed to generate the
active protease. Following activation, this protease hydrolyzes
proteins within specialized neutrophil lysosomes, called azurophil
granules, as well as proteins of the extracellular matrix. The
enzyme may play a role in degenerative and inflammatory diseases
through proteolysis of collagen-IV and elastin. This protein also
degrades the outer membrane protein A (OmpA) of E. coli as well as
the virulence factors of such bacteria as Shigella, Salmonella and
Yersinia. Mutations in this gene are associated with cyclic
neutropenia and severe congenital neutropenia (SCN). This gene is
present in a gene cluster on chromosome 19. [provided by RefSeq,
Jan 2016].
Publication Note: This RefSeq record includes a subset of the
publications that are available for this gene. Please see the Gene
record to access additional publications.
##Evidence-Data-START##
Transcript exon combination :: M34379.1, X05875.1 [ECO:0000332]
RNAseq introns :: single sample supports all introns
SAMEA1968540, SAMEA2142348
[ECO:0000348]
##Evidence-Data-END##
##RefSeq-Attributes-START##
MANE Ensembl match :: ENST00000263621.2/ ENSP00000263621.1
RefSeq Select criteria :: based on conservation, expression,
longest protein
##RefSeq-Attributes-END##
FEATURES Location/Qualifiers
source 1..267
/organism="Homo sapiens"
/db_xref="taxon:9606"
/chromosome="19"
/map="19p13.3"
Protein 1..267
/product="neutrophil elastase preproprotein"
/EC_number="3.4.21.37"
/note="medullasin; elastase 2, neutrophil; bone marrow
serine protease; leukocyte elastase; polymorphonuclear
elastase; granulocyte-derived elastase; elastase-2; PMN
elastase"
/calculated_mol_wt=25778
sig_peptide 1..27
/inference="COORDINATES: ab initio prediction:SignalP:4.0"
/calculated_mol_wt=2759
mat_peptide 30..267
/product="Neutrophil elastase"
/experiment="experimental evidence, no additional details
recorded"
/note="propagated from UniProtKB/Swiss-Prot (P08246.1)"
/calculated_mol_wt=25562
Region 30..245
/region_name="Tryp_SPc"
/note="Trypsin-like serine protease; Many of these are
synthesized as inactive precursor zymogens that are
cleaved during limited proteolysis to generate their
active forms. Alignment contains also inactive enzymes
that have substitutions of the catalytic triad...;
cd00190"
/db_xref="CDD:238113"
Site 30
/site_type="cleavage"
/db_xref="CDD:238113"
Site order(70,117,202)
/site_type="active"
/db_xref="CDD:238113"
Site 88
/site_type="glycosylation"
/experiment="experimental evidence, no additional details
recorded"
/note="N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:19159218}; propagated from
UniProtKB/Swiss-Prot (P08246.1)"
Site 124
/site_type="glycosylation"
/experiment="experimental evidence, no additional details
recorded"
/note="N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:3550808}; propagated from
UniProtKB/Swiss-Prot (P08246.1)"
Site 173
/site_type="glycosylation"
/experiment="experimental evidence, no additional details
recorded"
/note="N-linked (GlcNAc...) asparagine.
{ECO:0000269|PubMed:19159218, ECO:0000269|PubMed:3550808};
propagated from UniProtKB/Swiss-Prot (P08246.1)"
Site order(196,217,219)
/site_type="other"
/note="substrate binding sites [chemical binding]"
/db_xref="CDD:238113"
CDS 1..267
/gene="ELANE"
/gene_synonym="ELA2; GE; HLE; HNE; NE; PMN-E; SCN1"
/coded_by="NM_001972.4:27..830"
/db_xref="CCDS:CCDS12045.1"
/db_xref="GeneID:1991"
/db_xref="HGNC:HGNC:3309"
/db_xref="MIM:130130"
ORIGIN
1 mtlgrrlacl flacvlpall lggtalasei vggrrarpha wpfmvslqlr gghfcgatli
61 apnfvmsaah cvanvnvrav rvvlgahnls rreptrqvfa vqrifengyd pvnllndivi
121 lqlngsatin anvqvaqlpa qgrrlgngvq clamgwgllg rnrgiasvlq elnvtvvtsl
181 crrsnvctlv rgrqagvcfg dsgsplvcng lihgiasfvr ggcasglypd afapvaqfvn
241 widsiiqrse dnpcphprdp dpasrth
//
