ILEU_HUMAN
ID ILEU_HUMAN Reviewed; 379 AA.
AC P30740; A8K5L2; B4DNT0; Q53FB9; Q5W0E1; Q9UDF8;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-APR-1993, sequence version 1.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Leukocyte elastase inhibitor;
DE Short=LEI;
DE AltName: Full=Monocyte/neutrophil elastase inhibitor;
DE Short=EI;
DE Short=M/NEI;
DE AltName: Full=Peptidase inhibitor 2;
DE Short=PI-2;
DE AltName: Full=Serpin B1;
GN Name=SERPINB1; Synonyms=ELANH2, MNEI, PI2;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1376927; DOI=10.1073/pnas.89.12.5635;
RA Remold-O'Donnell E., Chin J., Alberts M.;
RT "Sequence and molecular characterization of human monocyte/neutrophil
RT elastase inhibitor.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:5635-5639(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=9630619; DOI=10.1016/s0378-1119(98)00189-9;
RA Zeng W., Silverman G.A., Remold-O'Donnell E.;
RT "Structure and sequence of human M/NEI (monocyte/neutrophil elastase
RT inhibitor), an Ov-serpin family gene.";
RL Gene 213:179-187(1998).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
RC TISSUE=Lung, and Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Small intestine;
RA Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S.;
RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cervix;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 1-10, AND ACETYLATION AT MET-1.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R.,
RA Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass spectrometric
RT identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [9]
RP PROTEIN SEQUENCE OF 111-129; 216-244 AND 255-274.
RX PubMed=7578269; DOI=10.1016/0167-4889(95)00113-7;
RA Packard B.Z., Lee S.S., Remold-O'Donnell E., Komoriya A.;
RT "A serpin from human tumor cells with direct lymphoid immunomodulatory
RT activity: mitogenic stimulation of human tumor-infiltrating lymphocytes.";
RL Biochim. Biophys. Acta 1269:41-50(1995).
RN [10]
RP PROTEIN SEQUENCE OF 178-185; 204-210 AND 364-371.
RC TISSUE=Keratinocyte;
RX PubMed=1286667; DOI=10.1002/elps.11501301199;
RA Rasmussen H.H., van Damme J., Puype M., Gesser B., Celis J.E.,
RA Vandekerckhove J.;
RT "Microsequences of 145 proteins recorded in the two-dimensional gel protein
RT database of normal human epidermal keratinocytes.";
RL Electrophoresis 13:960-969(1992).
RN [11]
RP FUNCTION, REACTIVE SITES, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=11747453; DOI=10.1021/bi0113925;
RA Cooley J., Takayama T.K., Shapiro S.D., Schechter N.M.,
RA Remold-O'Donnell E.;
RT "The serpin MNEI inhibits elastase-like and chymotrypsin-like serine
RT proteases through efficient reactions at two active sites.";
RL Biochemistry 40:15762-15770(2001).
RN [12]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-137 AND LYS-177, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [13]
RP TISSUE SPECIFICITY.
RX PubMed=21248149; DOI=10.1189/jlb.0810461;
RA Benarafa C., LeCuyer T.E., Baumann M., Stolley J.M., Cremona T.P.,
RA Remold-O'Donnell E.;
RT "SerpinB1 protects the mature neutrophil reserve in the bone marrow.";
RL J. Leukoc. Biol. 90:21-29(2011).
RN [14]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [16]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-300, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [17]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=26701651; DOI=10.1016/j.cmet.2015.12.001;
RA El Ouaamari A., Dirice E., Gedeon N., Hu J., Zhou J.Y., Shirakawa J.,
RA Hou L., Goodman J., Karampelias C., Qiang G., Boucher J., Martinez R.,
RA Gritsenko M.A., De Jesus D.F., Kahraman S., Bhatt S., Smith R.D.,
RA Beer H.D., Jungtrakoon P., Gong Y., Goldfine A.B., Liew C.W., Doria A.,
RA Andersson O., Qian W.J., Remold-O'Donnell E., Kulkarni R.N.;
RT "SerpinB1 Promotes Pancreatic beta Cell Proliferation.";
RL Cell Metab. 23:194-205(2016).
RN [18]
RP FUNCTION, INTERACTION WITH CASP1; CASP4; CASP5 AND PRTN3, MUTAGENESIS OF
RP PHE-343 AND CYS-344, AND DOMAIN.
RX PubMed=30692621; DOI=10.1038/s41590-018-0303-z;
RA Choi Y.J., Kim S., Choi Y., Nielsen T.B., Yan J., Lu A., Ruan J., Lee H.R.,
RA Wu H., Spellberg B., Jung J.U.;
RT "SERPINB1-mediated checkpoint of inflammatory caspase activation.";
RL Nat. Immunol. 20:276-287(2019).
RN [19]
RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) IN COMPLEX WITH GZMH, SUBCELLULAR
RP LOCATION, SUBUNIT, AND FUNCTION.
RX PubMed=23269243; DOI=10.4049/jimmunol.1202542;
RA Wang L., Li Q., Wu L., Liu S., Zhang Y., Yang X., Zhu P., Zhang H.,
RA Zhang K., Lou J., Liu P., Tong L., Sun F., Fan Z.;
RT "Identification of SERPINB1 as a physiological inhibitor of human granzyme
RT H.";
RL J. Immunol. 190:1319-1330(2013).
CC -!- FUNCTION: Neutrophil serine protease inhibitor that plays an essential
CC role in the regulation of the innate immune response, inflammation and
CC cellular homeostasis (PubMed:30692621). Acts primarily to protect the
CC cell from proteases released in the cytoplasm during stress or
CC infection. These proteases are important in killing microbes but when
CC released from granules, these potent enzymes also destroy host proteins
CC and contribute to mortality. Regulates the activity of the neutrophil
CC proteases elastase, cathepsin G, proteinase-3, chymase, chymotrypsin,
CC and kallikrein-3 (PubMed:11747453, PubMed:30692621). Acts also as a
CC potent intracellular inhibitor of GZMH by directly blocking its
CC proteolytic activity (PubMed:23269243). During inflammation, limits the
CC activity of inflammatory caspases CASP1, CASP4 and CASP5 by suppressing
CC their caspase-recruitment domain (CARD) oligomerization and enzymatic
CC activation (PubMed:30692621). When secreted, promotes the proliferation
CC of beta-cells via its protease inhibitory function (PubMed:26701651).
CC {ECO:0000269|PubMed:11747453, ECO:0000269|PubMed:23269243,
CC ECO:0000269|PubMed:26701651, ECO:0000269|PubMed:30692621}.
CC -!- SUBUNIT: Monomer (PubMed:23269243). Interacts (via C-terminus) with
CC CASP1; CASP4 (via CARD domain) and CASP5; these interactions regulate
CC the activity of inflammatory caspases (PubMed:30692621). Interacts with
CC PRTN3 (PubMed:30692621). Interacts with GZMH (PubMed:23269243).
CC {ECO:0000269|PubMed:23269243, ECO:0000269|PubMed:30692621}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:26701651}. Cytoplasm
CC {ECO:0000269|PubMed:23269243}. Cytolytic granule
CC {ECO:0000269|PubMed:23269243}. Early endosome
CC {ECO:0000269|PubMed:23269243}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P30740-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P30740-2; Sequence=VSP_056511;
CC -!- TISSUE SPECIFICITY: In human bone marrow, present in all CD45+
CC populations. Expression levels are highest in the neutrophil lineage,
CC intermediate in monocytic, and lowest in lymphocytic lineage. Within
CC the neutrophil lineage, expression is highest in promyelocytes.
CC {ECO:0000269|PubMed:21248149}.
CC -!- DOMAIN: Reactive bond 1 is specific for reaction with chymotrypsin-like
CC protease such as cathepsin G, chymotrypsin, chymase or granzyme H,
CC while reactive bond 2 is specific for reaction with elastase-like
CC protease such as neutrophil elastase, proteinase-3, pancreatic elastase
CC or PSA.
CC -!- SIMILARITY: Belongs to the serpin family. Ov-serpin subfamily.
CC {ECO:0000305}.
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DR EMBL; M93056; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AF053630; AAC31394.1; -; Genomic_DNA.
DR EMBL; AK291327; BAF84016.1; -; mRNA.
DR EMBL; AK298044; BAG60342.1; -; mRNA.
DR EMBL; BT006928; AAP35574.1; -; mRNA.
DR EMBL; AK223370; BAD97090.1; -; mRNA.
DR EMBL; AL139092; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC009015; AAH09015.1; -; mRNA.
DR CCDS; CCDS4477.1; -. [P30740-1]
DR PIR; S27383; S27383.
DR RefSeq; NP_109591.1; NM_030666.3. [P30740-1]
DR RefSeq; XP_011512635.1; XM_011514333.1. [P30740-1]
DR RefSeq; XP_011512636.1; XM_011514334.2. [P30740-1]
DR PDB; 4GA7; X-ray; 2.90 A; A/B=1-379.
DR PDBsum; 4GA7; -.
DR AlphaFoldDB; P30740; -.
DR SMR; P30740; -.
DR BioGRID; 108307; 53.
DR IntAct; P30740; 16.
DR STRING; 9606.ENSP00000370115; -.
DR MEROPS; I04.006; -.
DR GlyGen; P30740; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; P30740; -.
DR MetOSite; P30740; -.
DR PhosphoSitePlus; P30740; -.
DR BioMuta; SERPINB1; -.
DR DMDM; 266344; -.
DR OGP; P30740; -.
DR REPRODUCTION-2DPAGE; IPI00027444; -.
DR CPTAC; CPTAC-131; -.
DR CPTAC; CPTAC-132; -.
DR EPD; P30740; -.
DR jPOST; P30740; -.
DR MassIVE; P30740; -.
DR MaxQB; P30740; -.
DR PaxDb; P30740; -.
DR PeptideAtlas; P30740; -.
DR PRIDE; P30740; -.
DR ProteomicsDB; 4721; -.
DR ProteomicsDB; 54734; -. [P30740-1]
DR Antibodypedia; 9274; 554 antibodies from 30 providers.
DR DNASU; 1992; -.
DR Ensembl; ENST00000380739.6; ENSP00000370115.5; ENSG00000021355.13. [P30740-1]
DR GeneID; 1992; -.
DR KEGG; hsa:1992; -.
DR MANE-Select; ENST00000380739.6; ENSP00000370115.5; NM_030666.4; NP_109591.1.
DR CTD; 1992; -.
DR DisGeNET; 1992; -.
DR GeneCards; SERPINB1; -.
DR HGNC; HGNC:3311; SERPINB1.
DR HPA; ENSG00000021355; Tissue enhanced (bone marrow, esophagus).
DR MIM; 130135; gene.
DR neXtProt; NX_P30740; -.
DR OpenTargets; ENSG00000021355; -.
DR PharmGKB; PA35046; -.
DR VEuPathDB; HostDB:ENSG00000021355; -.
DR eggNOG; KOG2392; Eukaryota.
DR GeneTree; ENSGT00940000154573; -.
DR HOGENOM; CLU_023330_0_2_1; -.
DR InParanoid; P30740; -.
DR OMA; IDVHVRL; -.
DR PhylomeDB; P30740; -.
DR TreeFam; TF352619; -.
DR PathwayCommons; P30740; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; P30740; -.
DR BioGRID-ORCS; 1992; 16 hits in 1084 CRISPR screens.
DR ChiTaRS; SERPINB1; human.
DR GeneWiki; SERPINB1; -.
DR GenomeRNAi; 1992; -.
DR Pharos; P30740; Tbio.
DR PRO; PR:P30740; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; P30740; protein.
DR Bgee; ENSG00000021355; Expressed in esophagus squamous epithelium and 192 other tissues.
DR ExpressionAtlas; P30740; baseline and differential.
DR Genevisible; P30740; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0044194; C:cytolytic granule; IEA:UniProtKB-SubCell.
DR GO; GO:0036464; C:cytoplasmic ribonucleoprotein granule; IDA:HPA.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:0030414; F:peptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; NAS:UniProtKB.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; IDA:UniProtKB.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IMP:UniProtKB.
DR GO; GO:0044342; P:type B pancreatic cell proliferation; IDA:UniProtKB.
DR Gene3D; 2.30.39.10; -; 1.
DR Gene3D; 3.30.497.10; -; 1.
DR InterPro; IPR015557; Serpin_B1.
DR InterPro; IPR023795; Serpin_CS.
DR InterPro; IPR023796; Serpin_dom.
DR InterPro; IPR000215; Serpin_fam.
DR InterPro; IPR036186; Serpin_sf.
DR InterPro; IPR042178; Serpin_sf_1.
DR InterPro; IPR042185; Serpin_sf_2.
DR PANTHER; PTHR11461; PTHR11461; 1.
DR PANTHER; PTHR11461:SF180; PTHR11461:SF180; 1.
DR Pfam; PF00079; Serpin; 1.
DR SMART; SM00093; SERPIN; 1.
DR SUPFAM; SSF56574; SSF56574; 1.
DR PROSITE; PS00284; SERPIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Cytoplasm;
KW Direct protein sequencing; Endosome; Lysosome; Phosphoprotein;
KW Protease inhibitor; Reference proteome; Secreted;
KW Serine protease inhibitor.
FT CHAIN 1..379
FT /note="Leukocyte elastase inhibitor"
FT /id="PRO_0000094101"
FT REGION 351..379
FT /note="CARD-binding motif (CBM)"
FT /evidence="ECO:0000269|PubMed:30692621"
FT SITE 343..344
FT /note="Reactive bond 1"
FT SITE 344..345
FT /note="Reactive bond 2"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000269|PubMed:12665801,
FT ECO:0007744|PubMed:22814378"
FT MOD_RES 137
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 177
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 300
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..151
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_056511"
FT VARIANT 82
FT /note="A -> V (in dbSNP:rs34825616)"
FT /id="VAR_051945"
FT MUTAGEN 343
FT /note="F->A: Loss of proteinase-3-binding activity but
FT caspase-binding activity remains unaffected; in association
FT with A-344."
FT /evidence="ECO:0000269|PubMed:30692621"
FT MUTAGEN 344
FT /note="C->A: Loss of proteinase-3-binding activity but
FT caspase-binding activity remains unaffected; in association
FT with A-343."
FT /evidence="ECO:0000269|PubMed:30692621"
FT CONFLICT 137
FT /note="K -> R (in Ref. 4; AAP35574)"
FT /evidence="ECO:0000305"
FT CONFLICT 149
FT /note="A -> V (in Ref. 3; BAF84016)"
FT /evidence="ECO:0000305"
FT CONFLICT 264
FT /note="L -> F (in Ref. 3; BAF84016)"
FT /evidence="ECO:0000305"
FT CONFLICT 272
FT /note="Missing (in Ref. 9; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 329
FT /note="E -> K (in Ref. 3; BAF84016)"
FT /evidence="ECO:0000305"
FT HELIX 3..22
FT /evidence="ECO:0007829|PDB:4GA7"
FT STRAND 24..26
FT /evidence="ECO:0007829|PDB:4GA7"
FT STRAND 28..30
FT /evidence="ECO:0007829|PDB:4GA7"
FT HELIX 32..43
FT /evidence="ECO:0007829|PDB:4GA7"
FT HELIX 48..57
FT /evidence="ECO:0007829|PDB:4GA7"
FT HELIX 60..62
FT /evidence="ECO:0007829|PDB:4GA7"
FT HELIX 66..77
FT /evidence="ECO:0007829|PDB:4GA7"
FT STRAND 83..95
FT /evidence="ECO:0007829|PDB:4GA7"
FT HELIX 102..111
FT /evidence="ECO:0007829|PDB:4GA7"
FT STRAND 116..119
FT /evidence="ECO:0007829|PDB:4GA7"
FT HELIX 121..139
FT /evidence="ECO:0007829|PDB:4GA7"
FT TURN 140..142
FT /evidence="ECO:0007829|PDB:4GA7"
FT STRAND 159..168
FT /evidence="ECO:0007829|PDB:4GA7"
FT STRAND 171..173
FT /evidence="ECO:0007829|PDB:4GA7"
FT TURN 177..179
FT /evidence="ECO:0007829|PDB:4GA7"
FT STRAND 181..188
FT /evidence="ECO:0007829|PDB:4GA7"
FT STRAND 191..209
FT /evidence="ECO:0007829|PDB:4GA7"
FT TURN 210..213
FT /evidence="ECO:0007829|PDB:4GA7"
FT STRAND 214..221
FT /evidence="ECO:0007829|PDB:4GA7"
FT STRAND 224..235
FT /evidence="ECO:0007829|PDB:4GA7"
FT STRAND 238..242
FT /evidence="ECO:0007829|PDB:4GA7"
FT HELIX 244..249
FT /evidence="ECO:0007829|PDB:4GA7"
FT HELIX 252..259
FT /evidence="ECO:0007829|PDB:4GA7"
FT HELIX 261..263
FT /evidence="ECO:0007829|PDB:4GA7"
FT STRAND 265..274
FT /evidence="ECO:0007829|PDB:4GA7"
FT STRAND 276..283
FT /evidence="ECO:0007829|PDB:4GA7"
FT HELIX 285..290
FT /evidence="ECO:0007829|PDB:4GA7"
FT HELIX 295..297
FT /evidence="ECO:0007829|PDB:4GA7"
FT TURN 299..301
FT /evidence="ECO:0007829|PDB:4GA7"
FT TURN 305..307
FT /evidence="ECO:0007829|PDB:4GA7"
FT STRAND 315..326
FT /evidence="ECO:0007829|PDB:4GA7"
FT STRAND 345..347
FT /evidence="ECO:0007829|PDB:4GA7"
FT STRAND 349..353
FT /evidence="ECO:0007829|PDB:4GA7"
FT STRAND 358..364
FT /evidence="ECO:0007829|PDB:4GA7"
FT TURN 365..368
FT /evidence="ECO:0007829|PDB:4GA7"
FT STRAND 369..376
FT /evidence="ECO:0007829|PDB:4GA7"
SQ SEQUENCE 379 AA; 42742 MW; BAAE08DFCBCD8CD3 CRC64;
MEQLSSANTR FALDLFLALS ENNPAGNIFI SPFSISSAMA MVFLGTRGNT AAQLSKTFHF
NTVEEVHSRF QSLNADINKR GASYILKLAN RLYGEKTYNF LPEFLVSTQK TYGADLASVD
FQHASEDARK TINQWVKGQT EGKIPELLAS GMVDNMTKLV LVNAIYFKGN WKDKFMKEAT
TNAPFRLNKK DRKTVKMMYQ KKKFAYGYIE DLKCRVLELP YQGEELSMVI LLPDDIEDES
TGLKKIEEQL TLEKLHEWTK PENLDFIEVN VSLPRFKLEE SYTLNSDLAR LGVQDLFNSS
KADLSGMSGA RDIFISKIVH KSFVEVNEEG TEAAAATAGI ATFCMLMPEE NFTADHPFLF
FIRHNSSGSI LFLGRFSSP
