| 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,
| ELANE |
neutrophil elastase preproprotein [Homo sapiens]
NCBI Reference Sequence: NP_001963.1
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 //
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