ILEUA_MOUSE
ID ILEUA_MOUSE Reviewed; 379 AA.
AC Q9D154; Q3TV23; Q5SUV7; Q9D0S8; Q9D7S8;
DT 29-MAY-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2001, sequence version 1.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=Leukocyte elastase inhibitor A;
DE AltName: Full=Serine protease inhibitor EIA;
DE AltName: Full=Serpin B1a;
GN Name=Serpinb1a; Synonyms=Serpinb1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=129S6/SvEvTac, and C57BL/6J; TISSUE=Spleen;
RX PubMed=11863365; DOI=10.1006/geno.2002.6716;
RA Kaiserman D., Knaggs S., Scarff K.L., Gillard A., Mirza G., Cadman M.,
RA McKeone R., Denny P., Cooley J., Benarafa C., Remold-O'Donnell E.,
RA Ragoussis J., Bird P.I.;
RT "Comparison of human chromosome 6p25 with mouse chromosome 13 reveals a
RT greatly expanded ov-serpin gene repertoire in the mouse.";
RL Genomics 79:349-362(2002).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND TISSUE SPECIFICITY.
RC STRAIN=129S6/SvEvTac; TISSUE=Spleen;
RX PubMed=12189154; DOI=10.1074/jbc.m207080200;
RA Benarafa C., Cooley J., Zeng W., Bird P.I., Remold-O'Donnell E.;
RT "Characterization of four murine homologs of the human ov-serpin monocyte
RT neutrophil elastase inhibitor MNEI (SERPINB1).";
RL J. Biol. Chem. 277:42028-42033(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Embryo, Pancreas, and Stomach;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Colon;
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 [6]
RP PROTEIN SEQUENCE OF 57-69; 111-129; 175-186 AND 364-375, AND IDENTIFICATION
RP BY MASS SPECTROMETRY.
RC TISSUE=Hippocampus;
RA Lubec G., Klug S.;
RL Submitted (MAR-2007) to UniProtKB.
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Heart, Kidney, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [8]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=17664292; DOI=10.1084/jem.20070494;
RA Benarafa C., Priebe G.P., Remold-O'Donnell E.;
RT "The neutrophil serine protease inhibitor serpinb1 preserves lung defense
RT functions in Pseudomonas aeruginosa infection.";
RL J. Exp. Med. 204:1901-1909(2007).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=21683252; DOI=10.1016/b978-0-12-386471-0.00007-9;
RA Benarafa C.;
RT "The SerpinB1 knockout mouse a model for studying neutrophil protease
RT regulation in homeostasis and inflammation.";
RL Methods Enzymol. 499:135-148(2011).
RN [10]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
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 [11]
RP FUNCTION, SUBCELLULAR LOCATION, AND DISRUPTION PHENOTYPE.
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 [12]
RP FUNCTION, INTERACTION WITH CASP1 AND CASP4, AND DISRUPTION PHENOTYPE.
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).
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:17664292, PubMed:21683252,
CC PubMed:21248149, PubMed:30692621). Acts primarily to protect the cell
CC from proteases released in the cytoplasm during stress or infection
CC (PubMed:17664292). These proteases are important in killing microbes
CC but when released from granules, these potent enzymes also destroy host
CC proteins and contribute to mortality. Regulates the activity of the
CC neutrophil proteases elastase, cathepsin G, proteinase-3, chymase,
CC chymotrypsin, and kallikrein-3. Acts also as a potent intracellular
CC inhibitor of granzyme H (PubMed:12189154). During inflammation, limits
CC the activity of inflammatory caspases CASP1 and CASP4 by suppressing
CC their caspase-recruitment domain (CARD) oligomerization and enzymatic
CC activation (PubMed:30692621). In addition, promotes the proliferation
CC of beta-cells when secreted (PubMed:26701651).
CC {ECO:0000269|PubMed:12189154, ECO:0000269|PubMed:17664292,
CC ECO:0000269|PubMed:21248149, ECO:0000269|PubMed:21683252,
CC ECO:0000269|PubMed:26701651, ECO:0000269|PubMed:30692621}.
CC -!- SUBUNIT: Monomer. Interacts (via C-terminus) with CASP1 and CASP4 (via
CC CARD domain); these interactions regulate the activity of inflammatory
CC caspases. {ECO:0000269|PubMed:30692621}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:26701651}. Cytoplasm
CC {ECO:0000250|UniProtKB:P30740}. Cytolytic granule
CC {ECO:0000250|UniProtKB:P30740}. Early endosome
CC {ECO:0000250|UniProtKB:P30740}.
CC -!- TISSUE SPECIFICITY: Ubiquitous with higher expression in pancreas,
CC spleen and bone marrow. {ECO:0000269|PubMed:11863365,
CC ECO:0000269|PubMed:12189154}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice do not differ from wild-type in
CC growth, litter size or life span when maintained in a specific
CC pathogen-free environement (PubMed:17664292). However, they have
CC increased mortality in association with late-onset failed bacterial
CC clearance, and specifically increased neutrophil death
CC (PubMed:17664292, PubMed:30692621). Mutant mice also show a severe
CC defect in the bone marrow reserve of mature neutrophils demonstrating a
CC key role for in cellular homeostasis (PubMed:21683252,
CC PubMed:21248149). In addition, Serpinb1a-deficiency leads to
CC maladaptive beta-cell proliferation in insulin-resistant states
CC (PubMed:26701651). {ECO:0000269|PubMed:17664292,
CC ECO:0000269|PubMed:21248149, ECO:0000269|PubMed:21683252,
CC ECO:0000269|PubMed:26701651, ECO:0000269|PubMed:30692621}.
CC -!- SIMILARITY: Belongs to the serpin family. Ov-serpin subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB23335.1; Type=Frameshift; Evidence={ECO:0000305};
CC Sequence=CAI25648.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AF426024; AAL57486.1; -; mRNA.
DR EMBL; AF521697; AAM95933.1; -; Genomic_DNA.
DR EMBL; AK003930; BAB23079.1; -; mRNA.
DR EMBL; AK004500; BAB23335.1; ALT_FRAME; mRNA.
DR EMBL; AK008914; BAB25964.1; -; mRNA.
DR EMBL; AK160167; BAE35668.1; -; mRNA.
DR EMBL; AK160456; BAE35797.1; -; mRNA.
DR EMBL; AL645808; CAI25648.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BC011140; AAH11140.1; -; mRNA.
DR EMBL; BC104333; AAI04334.1; -; mRNA.
DR CCDS; CCDS26428.1; -.
DR RefSeq; NP_079705.2; NM_025429.2.
DR RefSeq; XP_006516787.1; XM_006516724.1.
DR AlphaFoldDB; Q9D154; -.
DR SMR; Q9D154; -.
DR BioGRID; 211307; 7.
DR IntAct; Q9D154; 1.
DR MINT; Q9D154; -.
DR STRING; 10090.ENSMUSP00000075690; -.
DR MEROPS; I04.006; -.
DR iPTMnet; Q9D154; -.
DR PhosphoSitePlus; Q9D154; -.
DR SwissPalm; Q9D154; -.
DR UCD-2DPAGE; Q9D154; -.
DR EPD; Q9D154; -.
DR jPOST; Q9D154; -.
DR MaxQB; Q9D154; -.
DR PaxDb; Q9D154; -.
DR PeptideAtlas; Q9D154; -.
DR PRIDE; Q9D154; -.
DR ProteomicsDB; 269475; -.
DR DNASU; 66222; -.
DR Ensembl; ENSMUST00000076352; ENSMUSP00000075690; ENSMUSG00000044734.
DR GeneID; 66222; -.
DR KEGG; mmu:66222; -.
DR UCSC; uc007pzu.1; mouse.
DR CTD; 66222; -.
DR MGI; MGI:1913472; Serpinb1a.
DR VEuPathDB; HostDB:ENSMUSG00000044734; -.
DR eggNOG; KOG2392; Eukaryota.
DR GeneTree; ENSGT00940000154573; -.
DR HOGENOM; CLU_023330_0_2_1; -.
DR InParanoid; Q9D154; -.
DR OMA; IDVHVRL; -.
DR OrthoDB; 1124079at2759; -.
DR PhylomeDB; Q9D154; -.
DR TreeFam; TF352619; -.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 66222; 0 hits in 71 CRISPR screens.
DR ChiTaRS; Serpinb1a; mouse.
DR PRO; PR:Q9D154; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q9D154; protein.
DR Bgee; ENSMUSG00000044734; Expressed in small intestine Peyer's patch and 218 other tissues.
DR ExpressionAtlas; Q9D154; baseline and differential.
DR Genevisible; Q9D154; MM.
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; ISO:MGI.
DR GO; GO:0005769; C:early endosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0030414; F:peptidase inhibitor activity; ISO:MGI.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IEA:UniProtKB-KW.
DR GO; GO:0019725; P:cellular homeostasis; IDA:UniProtKB.
DR GO; GO:0006954; P:inflammatory response; IDA:UniProtKB.
DR GO; GO:0010951; P:negative regulation of endopeptidase activity; ISO:MGI.
DR GO; GO:0032691; P:negative regulation of interleukin-1 beta production; IMP:UniProtKB.
DR GO; GO:0045088; P:regulation of innate immune response; IDA:UniProtKB.
DR GO; GO:0042176; P:regulation of protein catabolic process; IPI:MGI.
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 Cytoplasm; 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 A"
FT /id="PRO_0000289120"
FT REGION 351..379
FT /note="CARD-binding motif (CBM)"
FT /evidence="ECO:0000250|UniProtKB:P30740"
FT SITE 344..345
FT /note="Reactive bond"
FT /evidence="ECO:0000250"
FT MOD_RES 300
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q4G075"
FT CONFLICT 73
FT /note="L -> Q (in Ref. 3; BAB25964)"
FT /evidence="ECO:0000305"
FT CONFLICT 146
FT /note="E -> K (in Ref. 3; BAB23335)"
FT /evidence="ECO:0000305"
FT CONFLICT 154
FT /note="D -> N (in Ref. 3; BAB23335)"
FT /evidence="ECO:0000305"
FT CONFLICT 189
FT /note="K -> R (in Ref. 3; BAB23335)"
FT /evidence="ECO:0000305"
FT CONFLICT 193
FT /note="K -> R (in Ref. 3; BAB25964)"
FT /evidence="ECO:0000305"
FT CONFLICT 261
FT /note="R -> L (in Ref. 3; BAB23335)"
FT /evidence="ECO:0000305"
FT CONFLICT 265
FT /note="E -> K (in Ref. 3; BAB23335)"
FT /evidence="ECO:0000305"
FT CONFLICT 280
FT /note="E -> K (in Ref. 3; BAB23335)"
FT /evidence="ECO:0000305"
FT CONFLICT 290
FT /note="R -> P (in Ref. 3; BAB23335)"
FT /evidence="ECO:0000305"
FT CONFLICT 301
FT /note="K -> E (in Ref. 3; BAB23335)"
FT /evidence="ECO:0000305"
FT CONFLICT 313
FT /note="L -> S (in Ref. 3; BAB23335)"
FT /evidence="ECO:0000305"
FT CONFLICT 319
FT /note="V -> P (in Ref. 3; BAB23335)"
FT /evidence="ECO:0000305"
FT CONFLICT 324
FT /note="V -> F (in Ref. 3; BAB23335)"
FT /evidence="ECO:0000305"
FT CONFLICT 341
FT /note="A -> V (in Ref. 3; BAE35797)"
FT /evidence="ECO:0000305"
FT CONFLICT 362
FT /note="I -> M (in Ref. 3; BAB23335)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 379 AA; 42575 MW; F492F1EEB88E80B1 CRC64;
MEQLSSANTL FALELFQTLN ESSPTGNIFF SPFSISSALA MVILGAKGST AAQLSKTFHF
DSVEDIHSRF QSLNAEVSKR GASHTLKLAN RLYGEKTYNF LPEYLASTQK MYGADLAPVD
FLHASEDARK EINQWVKGQT EGKIPELLSV GVVDSMTKLV LVNAIYFKGM WEEKFMTEDT
TDAPFRLSKK DTKTVKMMYQ KKKFPFGYIS DLKCKVLEMP YQGGELSMVI LLPKDIEDES
TGLKKIEKQI TLEKLLEWTK RENLEFIDVH VKLPRFKIEE SYTLNSNLGR LGVQDLFSSS
KADLSGMSGS RDLFISKIVH KSFVEVNEEG TEAAAATGGI ATFCMLLPEE EFTVDHPFIF
FIRHNPTSNV LFLGRVCSP
