P30740 · ILEU_HUMAN
- ProteinLeukocyte elastase inhibitor
- GeneSERPINB1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids379 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Neutrophil serine protease inhibitor that plays an essential role in the regulation of the innate immune response, inflammation and cellular homeostasis (PubMed:30692621).
Acts primarily to protect the cell from proteases released in the cytoplasm during stress or infection. These proteases are important in killing microbes but when released from granules, these potent enzymes also destroy host proteins and contribute to mortality. Regulates the activity of the neutrophil proteases elastase, cathepsin G, proteinase-3, chymase, chymotrypsin, and kallikrein-3 (PubMed:11747453, PubMed:30692621).
Acts also as a potent intracellular inhibitor of GZMH by directly blocking its proteolytic activity (PubMed:23269243).
During inflammation, limits the activity of inflammatory caspases CASP1, CASP4 and CASP5 by suppressing their caspase-recruitment domain (CARD) oligomerization and enzymatic activation (PubMed:30692621).
When secreted, promotes the proliferation of beta-cells via its protease inhibitory function (PubMed:26701651).
Acts primarily to protect the cell from proteases released in the cytoplasm during stress or infection. These proteases are important in killing microbes but when released from granules, these potent enzymes also destroy host proteins and contribute to mortality. Regulates the activity of the neutrophil proteases elastase, cathepsin G, proteinase-3, chymase, chymotrypsin, and kallikrein-3 (PubMed:11747453, PubMed:30692621).
Acts also as a potent intracellular inhibitor of GZMH by directly blocking its proteolytic activity (PubMed:23269243).
During inflammation, limits the activity of inflammatory caspases CASP1, CASP4 and CASP5 by suppressing their caspase-recruitment domain (CARD) oligomerization and enzymatic activation (PubMed:30692621).
When secreted, promotes the proliferation of beta-cells via its protease inhibitory function (PubMed:26701651).
Features
Showing features for site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Site | 343-344 | Reactive bond 1 | ||||
Sequence: FC | ||||||
Site | 344-345 | Reactive bond 2 | ||||
Sequence: CM |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | collagen-containing extracellular matrix | |
Cellular Component | cytolytic granule | |
Cellular Component | cytoplasmic ribonucleoprotein granule | |
Cellular Component | early endosome | |
Cellular Component | extracellular exosome | |
Cellular Component | extracellular region | |
Cellular Component | extracellular space | |
Cellular Component | membrane | |
Cellular Component | secretory granule lumen | |
Molecular Function | peptidase inhibitor activity | |
Molecular Function | serine-type endopeptidase inhibitor activity | |
Biological Process | negative regulation of cell migration | |
Biological Process | negative regulation of endopeptidase activity | |
Biological Process | negative regulation of interleukin-1 beta production | |
Biological Process | type B pancreatic cell proliferation |
Keywords
- Molecular function
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameLeukocyte elastase inhibitor
- Short namesLEI
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionP30740
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Keywords
- Cellular component
Disease & Variants
Features
Showing features for natural variant, mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | VAR_051945 | 82 | in dbSNP:rs34825616 | |||
Sequence: A → V | ||||||
Mutagenesis | 343 | Loss of proteinase-3-binding activity but caspase-binding activity remains unaffected; in association with A-344. | ||||
Sequence: F → A | ||||||
Mutagenesis | 344 | Loss of proteinase-3-binding activity but caspase-binding activity remains unaffected; in association with A-343. | ||||
Sequence: C → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 376 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Modified residue | 1 | UniProt | N-acetylmethionine | ||||
Sequence: M | |||||||
Chain | PRO_0000094101 | 1-379 | UniProt | Leukocyte elastase inhibitor | |||
Sequence: MEQLSSANTRFALDLFLALSENNPAGNIFISPFSISSAMAMVFLGTRGNTAAQLSKTFHFNTVEEVHSRFQSLNADINKRGASYILKLANRLYGEKTYNFLPEFLVSTQKTYGADLASVDFQHASEDARKTINQWVKGQTEGKIPELLASGMVDNMTKLVLVNAIYFKGNWKDKFMKEATTNAPFRLNKKDRKTVKMMYQKKKFAYGYIEDLKCRVLELPYQGEELSMVILLPDDIEDESTGLKKIEEQLTLEKLHEWTKPENLDFIEVNVSLPRFKLEESYTLNSDLARLGVQDLFNSSKADLSGMSGARDIFISKIVHKSFVEVNEEGTEAAAATAGIATFCMLMPEENFTADHPFLFFIRHNSSGSILFLGRFSSP | |||||||
Modified residue (large scale data) | 72 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 137 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 166 | PRIDE | Phosphotyrosine | ||||
Sequence: Y | |||||||
Modified residue | 177 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue (large scale data) | 299 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 300 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 300 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 366 | PRIDE | Phosphoserine | ||||
Sequence: S |
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
Tissue specificity
In human bone marrow, present in all CD45+ populations. Expression levels are highest in the neutrophil lineage, intermediate in monocytic, and lowest in lymphocytic lineage. Within the neutrophil lineage, expression is highest in promyelocytes.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Monomer (PubMed:23269243).
Interacts (via C-terminus) with CASP1; CASP4 (via CARD domain) and CASP5; these interactions regulate the activity of inflammatory caspases (PubMed:30692621).
Interacts with PRTN3 (PubMed:30692621).
Interacts with GZMH (PubMed:23269243).
Interacts (via C-terminus) with CASP1; CASP4 (via CARD domain) and CASP5; these interactions regulate the activity of inflammatory caspases (PubMed:30692621).
Interacts with PRTN3 (PubMed:30692621).
Interacts with GZMH (PubMed:23269243).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 351-379 | CARD-binding motif (CBM) | ||||
Sequence: NFTADHPFLFFIRHNSSGSILFLGRFSSP |
Domain
Reactive bond 1 is specific for reaction with chymotrypsin-like protease such as cathepsin G, chymotrypsin, chymase or granzyme H, while reactive bond 2 is specific for reaction with elastase-like protease such as neutrophil elastase, proteinase-3, pancreatic elastase or PSA.
Sequence similarities
Belongs to the serpin family. Ov-serpin subfamily.
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
P30740-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length379
- Mass (Da)42,742
- Last updated1993-04-01 v1
- ChecksumBAAE08DFCBCD8CD3
P30740-2
- Name2
- Differences from canonical
- 1-151: Missing
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_056511 | 1-151 | in isoform 2 | |||
Sequence: Missing | ||||||
Sequence conflict | 137 | in Ref. 4; AAP35574 | ||||
Sequence: K → R | ||||||
Sequence conflict | 149 | in Ref. 3; BAF84016 | ||||
Sequence: A → V | ||||||
Sequence conflict | 264 | in Ref. 3; BAF84016 | ||||
Sequence: L → F | ||||||
Sequence conflict | 272 | in Ref. 9; AA sequence | ||||
Sequence: Missing | ||||||
Sequence conflict | 329 | in Ref. 3; BAF84016 | ||||
Sequence: E → K |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M93056 EMBL· GenBank· DDBJ | - | mRNA | No translation available. | |
AF053630 EMBL· GenBank· DDBJ | AAC31394.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AK291327 EMBL· GenBank· DDBJ | BAF84016.1 EMBL· GenBank· DDBJ | mRNA | ||
AK298044 EMBL· GenBank· DDBJ | BAG60342.1 EMBL· GenBank· DDBJ | mRNA | ||
BT006928 EMBL· GenBank· DDBJ | AAP35574.1 EMBL· GenBank· DDBJ | mRNA | ||
AK223370 EMBL· GenBank· DDBJ | BAD97090.1 EMBL· GenBank· DDBJ | mRNA | ||
AL139092 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
BC009015 EMBL· GenBank· DDBJ | AAH09015.1 EMBL· GenBank· DDBJ | mRNA |