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P08246 (ELNE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 158. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Neutrophil elastase

EC=3.4.21.37
Alternative name(s):
Bone marrow serine protease
Elastase-2
Human leukocyte elastase
Short name=HLE
Medullasin
PMN elastase
Gene names
Name:ELANE
Synonyms:ELA2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length267 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Modifies the functions of natural killer cells, monocytes and granulocytes. Inhibits C5a-dependent neutrophil enzyme release and chemotaxis. Ref.15

Catalytic activity

Hydrolysis of proteins, including elastin. Preferential cleavage: Val-|-Xaa > Ala-|-Xaa.

Subunit structure

Interacts with NOTCH2NL. Ref.16

Tissue specificity

Bone marrow cells.

Involvement in disease

Cyclic haematopoiesis (CH) [MIM:162800]: Autosomal dominant disease in which blood-cell production from the bone marrow oscillates with 21-day periodicity. Circulating neutrophils vary between almost normal numbers and zero. During intervals of neutropenia, affected individuals are at risk for opportunistic infection. Monocytes, platelets, lymphocytes and reticulocytes also cycle with the same frequency.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.16 Ref.22 Ref.23 Ref.26 Ref.35

Neutropenia, severe congenital 1, autosomal dominant (SCN1) [MIM:202700]: A disorder of hematopoiesis characterized by maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.23 Ref.24 Ref.25 Ref.26 Ref.27 Ref.28 Ref.29 Ref.30 Ref.31 Ref.32 Ref.33 Ref.34 Ref.35

Sequence similarities

Belongs to the peptidase S1 family. Elastase subfamily.

Contains 1 peptidase S1 domain.

Sequence caution

The sequence CAA29300.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Coding sequence diversityPolymorphism
   DiseaseDisease mutation
   DomainSignal
   Molecular functionHydrolase
Protease
Serine protease
   PTMDisulfide bond
Glycoprotein
Zymogen
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processacute inflammatory response to antigenic stimulus

Inferred from electronic annotation. Source: Ensembl

cellular calcium ion homeostasis

Non-traceable author statement Ref.15. Source: UniProtKB

collagen catabolic process

Traceable author statement. Source: Reactome

defense response to bacterium

Inferred from direct assay PubMed 14705961. Source: UniProtKB

extracellular matrix disassembly

Traceable author statement. Source: Reactome

extracellular matrix organization

Traceable author statement. Source: Reactome

leukocyte migration

Inferred from electronic annotation. Source: Ensembl

negative regulation of chemokine biosynthetic process

Inferred from direct assay PubMed 12223522. Source: UniProtKB

negative regulation of chemotaxis

Non-traceable author statement Ref.15. Source: UniProtKB

negative regulation of growth of symbiont in host

Inferred from electronic annotation. Source: Ensembl

negative regulation of inflammatory response

Non-traceable author statement Ref.15. Source: UniProtKB

negative regulation of interleukin-8 biosynthetic process

Inferred from direct assay PubMed 12223522. Source: UniProtKB

negative regulation of transcription from RNA polymerase II promoter

Inferred from mutant phenotype PubMed 19506020. Source: UniProt

neutrophil mediated killing of fungus

Inferred from electronic annotation. Source: Ensembl

phagocytosis

Inferred from electronic annotation. Source: Ensembl

positive regulation of MAP kinase activity

Non-traceable author statement PubMed 14730209. Source: UniProtKB

positive regulation of immune response

Inferred from electronic annotation. Source: Ensembl

positive regulation of interleukin-8 biosynthetic process

Inferred from direct assay PubMed 14730209. Source: UniProtKB

positive regulation of smooth muscle cell proliferation

Inferred from direct assay PubMed 15010259. Source: UniProtKB

protein catabolic process

Non-traceable author statement PubMed 12887060. Source: UniProtKB

proteolysis

Inferred from direct assay PubMed 11907569. Source: MGI

response to UV

Inferred from direct assay PubMed 11928814. Source: UniProtKB

response to lipopolysaccharide

Inferred from electronic annotation. Source: Ensembl

response to yeast

Inferred from electronic annotation. Source: Ensembl

   Cellular_componentcell surface

Inferred from direct assay PubMed 12114510. Source: UniProtKB

cytoplasm

Inferred from direct assay PubMed 19506020. Source: UniProt

extracellular region

Non-traceable author statement PubMed 12114510. Source: UniProtKB

extracellular vesicular exosome

Inferred from direct assay PubMed 19056867. Source: UniProt

secretory granule

Inferred from direct assay PubMed 11907569. Source: MGI

transcriptional repressor complex

Inferred from direct assay PubMed 19506020. Source: UniProt

   Molecular_functionRNA polymerase II transcription corepressor activity

Inferred from mutant phenotype PubMed 19506020. Source: UniProt

cytokine binding

Inferred from physical interaction PubMed 12393522. Source: UniProtKB

endopeptidase activity

Inferred from direct assay PubMed 12887060. Source: UniProtKB

heparin binding

Inferred from direct assay PubMed 11907569. Source: MGI

peptidase activity

Inferred from direct assay PubMed 11907569. Source: MGI

protease binding

Inferred from physical interaction PubMed 6980881. Source: BHF-UCL

serine-type endopeptidase activity

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Col17a1Q075632EBI-986345,EBI-6251005From a different organism.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2727 Potential
Propeptide28 – 292
PRO_0000027703
Chain30 – 267238Neutrophil elastase
PRO_0000027704

Regions

Domain30 – 247218Peptidase S1

Sites

Active site701Charge relay system
Active site1171Charge relay system
Active site2021Charge relay system

Amino acid modifications

Glycosylation881N-linked (GlcNAc...) Ref.17
Glycosylation1241N-linked (GlcNAc...) Ref.8
Glycosylation1731N-linked (GlcNAc...) Ref.8 Ref.17
Disulfide bond55 ↔ 71 Ref.8
Disulfide bond151 ↔ 208 Ref.8
Disulfide bond181 ↔ 187 Ref.8
Disulfide bond198 ↔ 223 Ref.8

Natural variations

Natural variant251A → V in SCN1. Ref.31 Ref.35
VAR_064512
Natural variant421P → L in SCN1. Ref.26 Ref.30 Ref.35
VAR_070696
Natural variant431F → L in SCN1 and CH. Ref.26 Ref.35
VAR_070697
Natural variant441M → R in SCN1. Ref.29
VAR_070698
Natural variant451V → E in SCN1. Ref.35
VAR_070699
Natural variant451V → L in CH. Ref.35
VAR_070700
Natural variant461S → C in SCN1. Ref.29
VAR_070701
Natural variant461S → F in CH and SCN1. Ref.26 Ref.35
VAR_070702
Natural variant471L → P in SCN1. Ref.26
VAR_070703
Natural variant471L → R in SCN1. Ref.35
VAR_070704
Natural variant491L → P in SCN1. Ref.35
VAR_070705
Natural variant531H → L in SCN1. Ref.26
VAR_070706
Natural variant531H → Q in CH.
VAR_070707
Natural variant531H → Y in SCN1. Ref.29
VAR_070708
Natural variant551C → S in SCN1. Ref.35
VAR_070709
Natural variant551C → Y in SCN1. Ref.24
VAR_038609
Natural variant561G → R in SCN1. Ref.35
VAR_070710
Natural variant571A → S in SCN1. Ref.33 Ref.35
VAR_070711
Natural variant571A → T in SCN1. Ref.23 Ref.35
VAR_038610
Natural variant571A → V in SCN1. Ref.28 Ref.35
VAR_070712
Natural variant591L → P in SCN1. Ref.32 Ref.35
VAR_070713
Natural variant60 – 612IA → R.
VAR_070714
Natural variant601I → T in SCN1. Ref.23 Ref.35
VAR_038611
Natural variant611A → V in SCN1 and CH. Ref.22 Ref.35
VAR_070715
Natural variant651Missing in SCN1. Ref.35
VAR_070716
Natural variant66 – 705Missing in SCN1.
VAR_070717
Natural variant671S → W in SCN1. Ref.35
VAR_070718
Natural variant711C → F in SCN1. Ref.35
VAR_070719
Natural variant711C → R in SCN1. Ref.25 Ref.35
Corresponds to variant rs28931611 [ dbSNP | Ensembl ].
VAR_038612
Natural variant711C → S in SCN1. Ref.23
VAR_038613
Natural variant711C → Y in SCN1. Ref.35
VAR_070720
Natural variant721V → G in SCN1. Ref.35
VAR_070721
Natural variant801V → G in SCN1. Ref.35
VAR_070722
Natural variant811R → P in SCN1 and CH. Ref.26 Ref.30 Ref.35
VAR_070723
Natural variant821V → M in SCN1 and CH. Ref.26 Ref.35
VAR_070724
Natural variant841L → P in SCN1. Ref.26 Ref.35
VAR_070725
Natural variant851G → E in SCN1. Ref.24 Ref.35
VAR_038614
Natural variant851G → R in SCN1. Ref.29
VAR_070726
Natural variant971Q → L in CH. Ref.35
VAR_070727
Natural variant981V → L in SCN1; located on the same allele as L-101; reduces proteolytic enzyme activity by slightly less than half; together with L-101 shows an additive effect with minimal remaining enzyme activity. Ref.27 Ref.35
VAR_038615
Natural variant981V → M in SCN1. Ref.35
VAR_070728
Natural variant1011V → L in SCN1; located on the same allele as L-98; reduces proteolytic enzyme activity by slightly less than half; together with L-98 shows an additive effect with minimal remaining enzyme activity. Ref.27 Ref.35
VAR_038616
Natural variant1011V → M in SCN1. Ref.23 Ref.30 Ref.35
Corresponds to variant rs28929494 [ dbSNP | Ensembl ].
VAR_038617
Natural variant1031R → L in SCN1. Ref.35
VAR_070729
Natural variant1031R → P in SCN1. Ref.35
VAR_070730
Natural variant1041I → N in CH. Ref.35
VAR_070731
Natural variant1181I → V. Ref.35
VAR_070732
Natural variant1201I → F in SCN1 and CH. Ref.35
VAR_070733
Natural variant1201I → N in SCN1. Ref.35
VAR_070734
Natural variant1201I → S in SCN1. Ref.35
VAR_070735
Natural variant1211L → P in SCN1. Ref.26 Ref.35
VAR_070736
Natural variant1231L → H in SCN1. Ref.35
VAR_070737
Natural variant1231L → PQL in SCN1.
VAR_038618
Natural variant1241N → I in SCN1. Ref.35
VAR_070738
Natural variant1251G → R. Ref.35
VAR_070739
Natural variant1261S → L in SCN1 and CH. Ref.23 Ref.24 Ref.26 Ref.30 Ref.35
Corresponds to variant rs137854450 [ dbSNP | Ensembl ].
VAR_038619
Natural variant1271A → D in SCN1. Ref.35
VAR_070740
Natural variant1271A → P in SCN1. Ref.26
VAR_070741
Natural variant1311A → T in SCN1; unknown pathological significance. Ref.34 Ref.35
VAR_070742
Natural variant1351V → M. Ref.35
VAR_070743
Natural variant1361A → D in SCN1. Ref.35
VAR_070744
Natural variant1391P → L in SCN1 and CH. Ref.23 Ref.26 Ref.35
Corresponds to variant rs28929493 [ dbSNP | Ensembl ].
VAR_038620
Natural variant1391P → R in SCN1. Ref.35
VAR_070745
Natural variant1431R → H in CH; unknown pathological significance. Ref.35
Corresponds to variant rs200993994 [ dbSNP | Ensembl ].
VAR_070746
Natural variant1511C → F in SCN1. Ref.35
VAR_070747
Natural variant1511C → S in SCN1. Ref.24
VAR_038621
Natural variant1511C → W in SCN1. Ref.35
VAR_070748
Natural variant1511C → Y in SCN1; unknown pathological significance. Ref.35
Corresponds to variant rs57246956 [ dbSNP | Ensembl ].
VAR_070749
Natural variant1521L → P in SCN1. Ref.26 Ref.34 Ref.35
VAR_070750
Natural variant1531A → D in SCN1. Ref.35
VAR_070751
Natural variant1531A → P in SCN1. Ref.35
VAR_070752
Natural variant1561W → C in SCN1. Ref.35
VAR_070753
Natural variant1561W → R in SCN1. Ref.35
VAR_070754
Natural variant1661A → T in SCN1; the patient also carries mutation Lys-116 in G6PC3. Ref.31 Ref.35
Corresponds to variant rs201788817 [ dbSNP | Ensembl ].
VAR_064513
Natural variant190 – 19910Missing in SCN1 and CH.
VAR_038622
Natural variant2031G → C in SCN1 and CH. Ref.29 Ref.35
VAR_070755
Natural variant2031G → R in SCN1. Ref.29 Ref.35
VAR_070756
Natural variant2051P → R in SCN1. Ref.24 Ref.35
VAR_038623
Natural variant2061L → F in CH. Ref.22
VAR_070757
Natural variant2061L → S in SCN1. Ref.35
VAR_070758
Natural variant2081C → G in SCN1. Ref.35
VAR_070759
Natural variant2091N → I in CH. Ref.35
VAR_070760
Natural variant2101G → V in SCN1. Ref.23
VAR_038624
Natural variant2101G → W in CH. Ref.35
VAR_070761
Natural variant2141G → E in SCN1. Ref.35
VAR_070762
Natural variant2141G → R in SCN1. Ref.23 Ref.35
VAR_038625
Natural variant2191V → I in CH and SCN1; unknown pathological significance. Ref.5 Ref.26 Ref.35
Corresponds to variant rs17216656 [ dbSNP | Ensembl ].
VAR_019237
Natural variant2201R → Q in CH and SCN1; loss of interaction with NOTCH2NL and loss of NOTCH2NL and NOTCH2 proteolytic cleavage. Ref.16 Ref.22 Ref.26 Ref.35
VAR_070763
Natural variant2331A → P in SCN1. Ref.35
VAR_070764
Natural variant2351V → E in SCN1. Ref.32 Ref.35
VAR_070765
Natural variant2351V → G in SCN1. Ref.34 Ref.35
VAR_070766
Natural variant2571P → L. Ref.5 Ref.35
Corresponds to variant rs17216663 [ dbSNP | Ensembl ].
VAR_019238
Natural variant2621P → L Found in patients with severe congenital or cyclic neutropenia. Ref.5 Ref.26
Corresponds to variant rs17216670 [ dbSNP | Ensembl ].
VAR_019239

Secondary structure

......................................... 267
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P08246 [UniParc].

Last modified August 1, 1988. Version 1.
Checksum: 3F7610DC33CAA4B9

FASTA26728,518
        10         20         30         40         50         60 
MTLGRRLACL FLACVLPALL LGGTALASEI VGGRRARPHA WPFMVSLQLR GGHFCGATLI 

        70         80         90        100        110        120 
APNFVMSAAH CVANVNVRAV RVVLGAHNLS RREPTRQVFA VQRIFENGYD PVNLLNDIVI 

       130        140        150        160        170        180 
LQLNGSATIN ANVQVAQLPA QGRRLGNGVQ CLAMGWGLLG RNRGIASVLQ ELNVTVVTSL 

       190        200        210        220        230        240 
CRRSNVCTLV RGRQAGVCFG DSGSPLVCNG LIHGIASFVR GGCASGLYPD AFAPVAQFVN 

       250        260 
WIDSIIQRSE DNPCPHPRDP DPASRTH 

« Hide

References

« Hide 'large scale' references
[1]"Nucleotide sequence of human bone marrow serine protease (medullasin) gene."
Nakamura H., Okano K., Aoki Y., Shimizu H., Naruto M.
Nucleic Acids Res. 15:9601-9601(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[2]"Structure of the human neutrophil elastase gene."
Takahashi H., Nukiwa T., Yoshimura K., Quick C.D., States D.J., Holmes M.D., Whang-Peng J., Knutsen T., Crystal R.G.
J. Biol. Chem. 263:14739-14747(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"The human neutrophil elastase gene. Analysis of the nucleotide sequence reveals three distinct classes of repetitive DNA."
Farley D., Travis J., Salvesen G.
Biol. Chem. Hoppe-Seyler 370:737-744(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Functional expression of human leukocyte elastase (HLE)/medullasin in eukaryotic cells."
Okano K., Aoki Y., Shimizu H., Naruto M.
Biochem. Biophys. Res. Commun. 167:1326-1332(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]NIEHS SNPs program
Submitted (APR-2004) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ILE-219; LEU-257 AND LEU-262.
[6]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Lung.
[7]"Molecular cloning of complementary DNA for human medullasin: an inflammatory serine protease in bone marrow cells."
Okano K., Aoki Y., Sakurai T., Kajitani M., Kanai S., Shimazu T., Shimizu H., Naruto M.
J. Biochem. 102:13-16(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 30-267.
[8]"Primary structure of human neutrophil elastase."
Sinha S., Watorek W., Karr S., Giles J., Bode W., Travis J.
Proc. Natl. Acad. Sci. U.S.A. 84:2228-2232(1987) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 30-247.
[9]Travis J., Giles P.J., Porcelli L., Reilly C.F., Baugh R., Powers J.
(In) Protein degradation in health and disease, Ciba Foundation Symposium, pp.75:51-68, Excerpta Medica, Amsterdam and Oxford (1980)
Cited for: PRELIMINARY PROTEIN SEQUENCE OF 30-103.
[10]"Antibiotic proteins of human polymorphonuclear leukocytes."
Gabay J.E., Scott R.W., Campanelli D., Griffith J., Wilde C., Marra M.N., Seeger M., Nathan C.F.
Proc. Natl. Acad. Sci. U.S.A. 86:5610-5614(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 30-49.
[11]"Use of proteinase 3 purified by reverse phase HPLC to detect autoantibodies in systemic vasculitis."
Gaskin G., Kendal H., Coulthart A., Turner N., Pusey C.D.
J. Immunol. Methods 180:25-33(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 30-49.
Tissue: Neutrophil.
[12]"Myelomonocytic cell lineage expression of the neutrophil elastase gene."
Takahashi H., Nukiwa T., Basset P., Cystal R.G.
J. Biol. Chem. 263:2543-2547(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 75-267.
[13]"Molecular cloning of human neutrophil elastase."
Farley D., Salvesen G.S., Travis J.
Biol. Chem. Hoppe-Seyler 369:3-7(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 123-267.
[14]"The primary structure and elastinolytic activity of medullasin (a serine protease of bone marrow)."
Aoki Y., Hase T.
Biochem. Biophys. Res. Commun. 178:501-506(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 262-267.
[15]"Human leukocyte elastase and cathepsin G are specific inhibitors of C5a-dependent neutrophil enzyme release and chemotaxis."
Tralau T., Meyer-Hoffert U., Schroder J.M., Wiedow O.
Exp. Dermatol. 13:316-325(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[16]"A novel notch protein, N2N, targeted by neutrophil elastase and implicated in hereditary neutropenia."
Duan Z., Li F.-Q., Wechsler J., Meade-White K., Williams K., Benson K.F., Horwitz M.
Mol. Cell. Biol. 24:58-70(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH NOTCH2NL, CHARACTERIZATION OF VARIANT CH GLN-220.
[17]"Glycoproteomics analysis of human liver tissue by combination of multiple enzyme digestion and hydrazide chemistry."
Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.
J. Proteome Res. 8:651-661(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-88 AND ASN-173.
Tissue: Liver.
[18]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[19]"Structure of human neutrophil elastase in complex with a peptide chloromethyl ketone inhibitor at 1.84-A resolution."
Navia M.A., McKeever B.M., Springer J.P., Lin T.-Y., Williams H.R., Fluder E.M., Dorn C.P., Hoogsteen K.
Proc. Natl. Acad. Sci. U.S.A. 86:7-11(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.84 ANGSTROMS).
[20]"The refined 2.3-A crystal structure of human leukocyte elastase in a complex with a valine chloromethyl ketone inhibitor."
Wei A.-Z., Mayr I., Bode W.
FEBS Lett. 234:367-373(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS).
[21]"X-ray crystal structure of the complex of human leukocyte elastase (PMN elastase) and the third domain of the turkey ovomucoid inhibitor."
Bode W., Wei A.-Z., Huber R., Meyer E., Travis J., Neumann S.
EMBO J. 5:2453-2458(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS).
[22]"Mutations in ELA2, encoding neutrophil elastase, define a 21-day biological clock in cyclic haematopoiesis."
Horwitz M., Benson K.F., Person R.E., Aprikyan A.G., Dale D.C.
Nat. Genet. 23:433-436(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS CH VAL-61; PHE-206 AND GLN-220.
[23]"Mutations in the gene encoding neutrophil elastase in congenital and cyclic neutropenia."
Dale D.C., Person R.E., Bolyard A.A., Aprikyan A.G., Bos C., Bonilla M.A., Boxer L.A., Kannourakis G., Zeidler C., Welte K., Benson K.F., Horwitz M.
Blood 96:2317-2322(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SCN1 THR-57; THR-60; SER-71; MET-101; LEU-126; LEU-139; VAL-210 AND ARG-214, VARIANT CH LEU-139.
[24]"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."
Ancliff P.J., Gale R.E., Liesner R., Hann I.M., Linch D.C.
Blood 98:2645-2650(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SCN1 TYR-55; GLU-85; PRO-GLN-LEU-123 INS; LEU-126; SER-151; 190-VAL--PHE-199 DEL AND ARG-205.
[25]"Paternal mosaicism proves the pathogenic nature of mutations in neutrophil elastase in severe congenital neutropenia."
Ancliff P.J., Gale R.E., Watts M.J., Liesner R., Hann I.M., Strobel S., Linch D.C.
Blood 100:707-709(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SCN1 ARG-71.
[26]"Mutations in the ELA2 gene correlate with more severe expression of neutropenia: a study of 81 patients from the French Neutropenia Register."
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.
Blood 103:4119-4125(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SCN1 LEU-42; PRO-47; LEU-53; PRO-81; PRO-84; PRO-121; PRO-127; LEU-139; PRO-152 AND 190-VAL--199-PHE DEL, VARIANTS CH LEU-43; PHE-46; MET-82; LEU-126; LEU-139; 190-VAL--199-PHE DEL; ILE-219 AND GLN-220, VARIANT LEU-262.
[27]"Double de novo mutations of ELA2 in cyclic and severe congenital neutropenia."
Salipante S.J., Benson K.F., Luty J., Hadavi V., Kariminejad R., Kariminejad M.H., Rezaei N., Horwitz M.S.
Hum. Mutat. 28:874-881(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SCN1 LEU-98 AND LEU-101, CHARACTERIZATION OF VARIANTS SCN1 LEU-98 AND LEU-101.
[28]"A novel mutation Ala57Val of the ELA2 gene in a Korean boy with severe congenital neutropenia."
Lee S.T., Yoon H.S., Kim H.J., Lee J.H., Park J.H., Kim S.H., Seo J.J., Im H.J.
Ann. Hematol. 88:593-595(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SCN1 VAL-57.
[29]"Homozygous HAX1 mutations in severe congenital neutropenia patients with sporadic disease: a novel mutation in two unrelated British kindreds."
Smith B.N., Ancliff P.J., Pizzey A., Khwaja A., Linch D.C., Gale R.E.
Br. J. Haematol. 144:762-770(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SCN1 ARG-44; CYS-46; TYR-53; ARG-85; ARG-203 AND CYS-203.
[30]"Ela2 mutations and clinical manifestations in familial congenital neutropenia."
Shiohara M., Shigemura T., Saito S., Tanaka M., Yanagisawa R., Sakashita K., Asada H., Ishii E., Koike K., Chin M., Kobayashi M., Koike K.
J. Pediatr. Hematol. Oncol. 31:319-324(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SCN1 LEU-42; PRO-81; MET-101 AND LEU-126.
[31]"Digenic mutations in severe congenital neutropenia."
Germeshausen M., Zeidler C., Stuhrmann M., Lanciotti M., Ballmaier M., Welte K.
Haematologica 95:1207-1210(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SCN1 VAL-25 AND THR-166.
[32]"Pegfilgrastim in children with severe congenital neutropenia."
Fioredda F., Calvillo M., Lanciotti M., Lanza T., Giunti L., Castagnola E., Lorenzi I., Tonelli R., Ghezzi P., Dufour C.
Pediatr. Blood Cancer 54:465-467(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SCN1 PRO-59 AND GLU-235.
[33]"Severe congenital neutropenia in a multigenerational family with a novel neutrophil elastase (ELANE) mutation."
van de Vosse E., Verhard E.M., Tool A.J., de Visser A.W., Kuijpers T.W., Hiemstra P.S., van Dissel J.T.
Ann. Hematol. 90:151-158(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT SCN1 SER-57.
[34]"Four novel ELANE mutations in patients with congenital neutropenia."
Kurnikova M., Maschan M., Dinova E., Shagina I., Finogenova N., Mamedova E., Polovtseva T., Shagin D., Shcherbina A.
Pediatr. Blood Cancer 57:332-335(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SCN1 THR-131; PRO-152; GLY-235 AND 190-VAL--199-PHE DEL.
[35]"The spectrum of ELANE mutations and their implications in severe congenital and cyclic neutropenia."
Germeshausen M., Deerberg S., Peter Y., Reimer C., Kratz C.P., Ballmaier M.
Hum. Mutat. 34:905-914(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS SCN1 VAL-25; LEU-42; LEU-43; GLU-45; PHE-46; ARG-47; PRO-49; SER-55; ARG-56; SER-57; THR-57; VAL-57; PRO-59; 60-ILE-ALA-61 DELINS ARG; THR-60; VAL-61; VAL-65 DEL; 66-MET--HIS-70 DEL; TRP-67; ARG-71; PHE-71; TYR-71; GLY-72; GLY-80; PRO-81; MET-82; PRO-84; GLU-85; LEU-98; MET-98; LEU-101; MET-101; LEU-103; PRO-103; ASN-120; PHE-120; SER-120; PRO-121; HIS-123; ILE-124; LEU-126; ASP-127; THR-131; ASP-136; ARG-139; LEU-139; PHE-151; TRP-151; TYR-151; PRO-152; ASP-153; PRO-153; ARG-156; CYS-156; THR-166; ARG-203; ARG-205; SER-206; GLY-208; ARG-214; GLU-214; ILE-219; GLN-220; PRO-233; GLU-235 AND GLY-235, VARIANTS CH LEU-45; VAL-61; PRO-81; LEU-97; ASN-104; PHE-120; LEU-126; LEU-139; HIS-143; 190-VAL--199-PHE DEL; CYS-203; ILE-209; TRP-210; ILE-219 AND GLN-220, VARIANTS VAL-118; ARG-125; MET-135 AND LEU-257.
+Additional computationally mapped references.

Web resources

CCHMC molecular genetics laboratory mutation database

ELA2 elastase, neutrophil expressed (ELANE)

ELA2base

ELA2 mutation db

GeneReviews
NIEHS-SNPs
Wikipedia

Elastase entry

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
Y00477 Genomic DNA. Translation: CAA68537.1.
M20203 expand/collapse EMBL AC list , M20199, M20200, M20201 Genomic DNA. Translation: AAA36359.1.
M34379 mRNA. Translation: AAA36173.1.
AY596461 Genomic DNA. Translation: AAS89303.1.
BC074816 mRNA. Translation: AAH74816.1.
BC074817 mRNA. Translation: AAH74817.1.
D00187 mRNA. Translation: BAA00128.1.
X05875 mRNA. Translation: CAA29299.1.
X05875 mRNA. Translation: CAA29300.1. Different initiation.
J03545 mRNA. Translation: AAA52378.1.
M27783 mRNA. Translation: AAA35792.1.
PIRELHUL. A31976.
RefSeqNP_001963.1. NM_001972.2.
XP_005259574.1. XM_005259517.1.
UniGeneHs.99863.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1B0FX-ray3.00A30-247[»]
1H1BX-ray2.00A/B30-247[»]
1HNEX-ray1.84E30-247[»]
1PPFX-ray1.80E30-247[»]
1PPGX-ray2.30E30-247[»]
2RG3X-ray1.80A30-247[»]
2Z7FX-ray1.70E30-247[»]
3Q76X-ray1.86A/B30-247[»]
3Q77X-ray2.00A30-247[»]
ProteinModelPortalP08246.
SMRP08246. Positions 30-247.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108306. 9 interactions.
IntActP08246. 4 interactions.
MINTMINT-1505052.
STRING9606.ENSP00000263621.

Chemistry

BindingDBP08246.
ChEMBLCHEMBL248.
DrugBankDB00058. Alpha-1-proteinase inhibitor.
DB00099. Filgrastim.
DB00019. Pegfilgrastim.
GuidetoPHARMACOLOGY2358.

Protein family/group databases

MEROPSS01.131.

Polymorphism databases

DMDM119292.

Proteomic databases

PaxDbP08246.
PeptideAtlasP08246.
PRIDEP08246.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000263621; ENSP00000263621; ENSG00000197561.
ENST00000590230; ENSP00000466090; ENSG00000197561.
GeneID1991.
KEGGhsa:1991.
UCSCuc002lqb.3. human.

Organism-specific databases

CTD1991.
GeneCardsGC19P000852.
HGNCHGNC:3309. ELANE.
HPACAB015409.
MIM130130. gene.
162800. phenotype.
202700. phenotype.
neXtProtNX_P08246.
Orphanet486. Autosomal dominant severe congenital neutropenia.
2686. Cyclic neutropenia.
PharmGKBPA27735.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5640.
HOGENOMHOG000251820.
HOVERGENHBG013304.
InParanoidP08246.
KOK01327.
OMALRGGHFC.
OrthoDBEOG7MKW6Q.
PhylomeDBP08246.

Enzyme and pathway databases

BRENDA3.4.21.37. 2681.
ReactomeREACT_118779. Extracellular matrix organization.
SABIO-RKP08246.

Gene expression databases

ArrayExpressP08246.
BgeeP08246.
CleanExHS_ELA2.
GenevestigatorP08246.

Family and domain databases

InterProIPR001254. Peptidase_S1.
IPR018114. Peptidase_S1_AS.
IPR001314. Peptidase_S1A.
IPR009003. Trypsin-like_Pept_dom.
[Graphical view]
PfamPF00089. Trypsin. 1 hit.
[Graphical view]
PRINTSPR00722. CHYMOTRYPSIN.
SMARTSM00020. Tryp_SPc. 1 hit.
[Graphical view]
SUPFAMSSF50494. SSF50494. 1 hit.
PROSITEPS50240. TRYPSIN_DOM. 1 hit.
PS00134. TRYPSIN_HIS. 1 hit.
PS00135. TRYPSIN_SER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP08246.
GeneWikiNeutrophil_elastase.
GenomeRNAi1991.
NextBio8051.
PROP08246.
SOURCESearch...

Entry information

Entry nameELNE_HUMAN
AccessionPrimary (citable) accession number: P08246
Secondary accession number(s): P09649, Q6B0D9, Q6LDP5
Entry history
Integrated into UniProtKB/Swiss-Prot: August 1, 1988
Last sequence update: August 1, 1988
Last modified: April 16, 2014
This is version 158 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM