SLPI_MOUSE
ID SLPI_MOUSE Reviewed; 131 AA.
AC P97430; O09081; O09082;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1997, sequence version 1.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Antileukoproteinase;
DE Short=ALP;
DE AltName: Full=Secretory leukocyte protease inhibitor {ECO:0000303|PubMed:9039268};
DE Flags: Precursor;
GN Name=Slpi;
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], FUNCTION, INDUCTION BY BACTERIAL
RP LIPOPOLYSACCHARIDE, AND TISSUE SPECIFICITY.
RX PubMed=9039268; DOI=10.1016/s0092-8674(00)81880-2;
RA Jin F.-Y., Nathan C.F., Radzioch D., Ding A.;
RT "Secretory leukocyte protease inhibitor: a macrophage product induced by
RT and antagonistic to bacterial lipopolysaccharide.";
RL Cell 88:417-426(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 26-51, FUNCTION,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=9126337; DOI=10.1006/bbrc.1997.6358;
RA Zitnik R.J., Zhang J., Kashem M.A., Kohno T., Lyons D.E., Wright C.D.,
RA Rosen E., Goldberg I., Hayday A.C.;
RT "The cloning and characterization of a murine secretory leukocyte protease
RT inhibitor cDNA.";
RL Biochem. Biophys. Res. Commun. 232:687-697(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION BY PNEUMONIA.
RC STRAIN=C57BL/6 X CBA; TISSUE=Lung;
RX PubMed=9351627; DOI=10.1164/ajrccm.156.4.9701075;
RA Abe T., Tominaga Y., Kikuchi T., Watanabe A., Satoh K., Watanabe Y.,
RA Nukiwa T.;
RT "Bacterial pneumonia causes augmented expression of the secretory
RT leukoprotease inhibitor gene in the murine lung.";
RL Am. J. Respir. Crit. Care Med. 156:1235-1240(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
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 [5]
RP DISRUPTION PHENOTYPE, FUNCTION, AND INDUCTION BY WOUNDING.
RX PubMed=11017147; DOI=10.1038/80489;
RA Ashcroft G.S., Lei K., Jin W., Longenecker G., Kulkarni A.B.,
RA Greenwell-Wild T., Hale-Donze H., McGrady G., Song X.Y., Wahl S.M.;
RT "Secretory leukocyte protease inhibitor mediates non-redundant functions
RT necessary for normal wound healing.";
RL Nat. Med. 6:1147-1153(2000).
RN [6]
RP INTERACTION WITH GRN.
RX PubMed=12526812; DOI=10.1016/s0092-8674(02)01141-8;
RA Zhu J., Nathan C., Jin W., Sim D., Ashcroft G.S., Wahl S.M., Lacomis L.,
RA Erdjument-Bromage H., Tempst P., Wright C.D., Ding A.;
RT "Conversion of proepithelin to epithelins: roles of SLPI and elastase in
RT host defense and wound repair.";
RL Cell 111:867-878(2002).
RN [7]
RP DISRUPTION PHENOTYPE, AND FUNCTION.
RX PubMed=12615907; DOI=10.1084/jem.20021824;
RA Nakamura A., Mori Y., Hagiwara K., Suzuki T., Sakakibara T., Kikuchi T.,
RA Igarashi T., Ebina M., Abe T., Miyazaki J., Takai T., Nukiwa T.;
RT "Increased susceptibility to LPS-induced endotoxin shock in secretory
RT leukoprotease inhibitor (SLPI)-deficient mice.";
RL J. Exp. Med. 197:669-674(2003).
RN [8]
RP DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION,
RP AND MUTAGENESIS OF 39-LYS-LYS-40; LYS-92 AND ARG-96.
RX PubMed=18322212; DOI=10.4049/jimmunol.180.6.4032;
RA Nishimura J., Saiga H., Sato S., Okuyama M., Kayama H., Kuwata H.,
RA Matsumoto S., Nishida T., Sawa Y., Akira S., Yoshikai Y., Yamamoto M.,
RA Takeda K.;
RT "Potent antimycobacterial activity of mouse secretory leukocyte protease
RT inhibitor.";
RL J. Immunol. 180:4032-4039(2008).
RN [9]
RP DISRUPTION PHENOTYPE, FUNCTION, AND INDUCTION.
RX PubMed=25030421; DOI=10.1189/jlb.4a0612-295rr;
RA McCartney-Francis N., Jin W., Belkaid Y., McGrady G., Wahl S.M.;
RT "Aberrant host defense against Leishmania major in the absence of SLPI.";
RL J. Leukoc. Biol. 96:917-929(2014).
CC -!- FUNCTION: Acid-stable proteinase inhibitor with strong affinities for
CC trypsin, chymotrypsin, elastase, and cathepsin G (PubMed:9126337).
CC Modulates the innate immune response after bacterial infection
CC (PubMed:12615907). Contributes to regulate the inflammatory and immune
CC responses to the intracellular parasite L.major (PubMed:25030421).
CC Down-regulates responses to bacterial lipopolysaccharide (LPS)
CC (PubMed:9039268, PubMed:12615907, PubMed:25030421). Plays a role in
CC regulating the activation of NF-kappa-B and inflammatory responses
CC (PubMed:11017147, PubMed:12615907). Has antimicrobial activity against
CC mycobacteria, but not against salmonella (PubMed:18322212). Contributes
CC to normal resistance against infection by M.tuberculosis
CC (PubMed:18322212). Required for normal resistance to L.major
CC (PubMed:25030421). Required for normal wound healing, probably by
CC preventing tissue damage by limiting protease activity
CC (PubMed:11017147, PubMed:25030421). Together with ELANE, required for
CC normal differentiation and proliferation of bone marrow myeloid cells
CC (By similarity). {ECO:0000250|UniProtKB:P03973,
CC ECO:0000269|PubMed:11017147, ECO:0000269|PubMed:12615907,
CC ECO:0000269|PubMed:18322212, ECO:0000269|PubMed:25030421,
CC ECO:0000269|PubMed:9039268, ECO:0000269|PubMed:9126337,
CC ECO:0000269|PubMed:9351627, ECO:0000305}.
CC -!- SUBUNIT: Interacts with GRN; interaction protects progranulin from
CC proteolysis. {ECO:0000269|PubMed:12526812}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:18322212,
CC ECO:0000269|PubMed:9126337}.
CC -!- TISSUE SPECIFICITY: Detected in bronchial epithelial cells
CC (PubMed:18322212). Detected in bronchoalveolar fluid after infection
CC with M.tuberculosis (at protein level) (PubMed:18322212). Highest
CC expression in lung, spleen, intestine and epididymis with lower levels
CC in liver and seminal vesicle. No expression in brain, heart, kidney and
CC muscle. {ECO:0000269|PubMed:18322212, ECO:0000269|PubMed:9039268,
CC ECO:0000269|PubMed:9126337, ECO:0000269|PubMed:9351627}.
CC -!- INDUCTION: Up-regulated by bacterial lipopolysaccharide
CC (PubMed:9039268, PubMed:25030421). Up-regulated in lung after infection
CC with M.tuberculosis (PubMed:18322212). Down-regulated by IFNG
CC (PubMed:9039268). Up-regulated in lung in response to bacterial
CC pneumonia (PubMed:9351627). Up-regulated in macrophages after exposure
CC to L.major (PubMed:25030421). Not up-regulated in spleen in response to
CC bacterial pneumonia (PubMed:9351627). Up-regulated in wounded skin
CC (PubMed:11017147). {ECO:0000269|PubMed:11017147,
CC ECO:0000269|PubMed:18322212, ECO:0000269|PubMed:25030421,
CC ECO:0000269|PubMed:9039268, ECO:0000269|PubMed:9351627}.
CC -!- DISRUPTION PHENOTYPE: Mutant mice show delayed epithelial wound healing
CC and an increased inflammatory response at the site of wounding,
CC possibly due to increased elastase activity (PubMed:11017147,
CC PubMed:25030421). Mutant mice show an increased tendency to die from
CC toxic shock after exposure to bacterial lipopolysaccharide (LPS)
CC (PubMed:12615907). Mutant mice are highly susceptible to
CC M.tuberculosis; all die within 50 days after infection
CC (PubMed:18322212). Mutant mice are highly susceptible infection by
CC L.major. Contrary to what is observed with wild-type, the parasites are
CC not restricted to the initial site of infection, but spread to spleen,
CC liver and bone morrow. The skin lesions at the initial site of
CC infection do not heal normally, but become bigger over time, in
CC parallel with the spread of the parasites. The inflammatory response at
CC the site of infection is more intense and persists longer than normal.
CC Increased protease activity is observed in these lesions and may be the
CC cause of the extensive tissue damage and necrosis (PubMed:25030421).
CC {ECO:0000269|PubMed:11017147, ECO:0000269|PubMed:12615907,
CC ECO:0000269|PubMed:18322212, ECO:0000269|PubMed:25030421}.
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DR EMBL; U73004; AAC53047.1; -; mRNA.
DR EMBL; U88093; AAC53140.1; -; mRNA.
DR EMBL; U94341; AAC53394.1; -; mRNA.
DR EMBL; BC028509; AAH28509.1; -; mRNA.
DR CCDS; CCDS17033.1; -.
DR RefSeq; NP_035544.1; NM_011414.3.
DR AlphaFoldDB; P97430; -.
DR SMR; P97430; -.
DR BioGRID; 203333; 1.
DR STRING; 10090.ENSMUSP00000104992; -.
DR MEROPS; I17.001; -.
DR PhosphoSitePlus; P97430; -.
DR PaxDb; P97430; -.
DR PRIDE; P97430; -.
DR ProteomicsDB; 261195; -.
DR Antibodypedia; 3705; 416 antibodies from 36 providers.
DR DNASU; 20568; -.
DR Ensembl; ENSMUST00000109367; ENSMUSP00000104992; ENSMUSG00000017002.
DR GeneID; 20568; -.
DR KEGG; mmu:20568; -.
DR UCSC; uc008nuj.1; mouse.
DR CTD; 6590; -.
DR MGI; MGI:109297; Slpi.
DR VEuPathDB; HostDB:ENSMUSG00000017002; -.
DR eggNOG; ENOG502SWIR; Eukaryota.
DR GeneTree; ENSGT00730000111217; -.
DR HOGENOM; CLU_105901_2_1_1; -.
DR InParanoid; P97430; -.
DR OMA; CPVVYGQ; -.
DR OrthoDB; 1560605at2759; -.
DR PhylomeDB; P97430; -.
DR TreeFam; TF338375; -.
DR Reactome; R-MMU-6798695; Neutrophil degranulation.
DR BioGRID-ORCS; 20568; 1 hit in 72 CRISPR screens.
DR PRO; PR:P97430; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P97430; protein.
DR Bgee; ENSMUSG00000017002; Expressed in esophagus and 127 other tissues.
DR ExpressionAtlas; P97430; baseline and differential.
DR Genevisible; P97430; MM.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; ISO:MGI.
DR GO; GO:0003677; F:DNA binding; ISO:MGI.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; ISO:MGI.
DR GO; GO:0003729; F:mRNA binding; ISO:MGI.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; ISS:UniProtKB.
DR GO; GO:0019731; P:antibacterial humoral response; IMP:UniProtKB.
DR GO; GO:0006955; P:immune response; IMP:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IMP:UniProtKB.
DR GO; GO:0035821; P:modulation of process of another organism; ISO:MGI.
DR GO; GO:0032091; P:negative regulation of protein binding; ISO:MGI.
DR GO; GO:0045071; P:negative regulation of viral genome replication; ISO:MGI.
DR GO; GO:0032496; P:response to lipopolysaccharide; IMP:UniProtKB.
DR Gene3D; 4.10.75.10; -; 2.
DR InterPro; IPR036645; Elafin-like_sf.
DR InterPro; IPR008197; WAP_dom.
DR Pfam; PF00095; WAP; 2.
DR PRINTS; PR00003; 4DISULPHCORE.
DR SMART; SM00217; WAP; 2.
DR SUPFAM; SSF57256; SSF57256; 2.
DR PROSITE; PS51390; WAP; 2.
PE 1: Evidence at protein level;
KW Antibiotic; Antimicrobial; Direct protein sequencing; Disulfide bond;
KW Immunity; Innate immunity; Protease inhibitor; Reference proteome; Repeat;
KW Secreted; Serine protease inhibitor; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000269|PubMed:9126337"
FT CHAIN 26..131
FT /note="Antileukoproteinase"
FT /id="PRO_0000041356"
FT DOMAIN 29..77
FT /note="WAP 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00722"
FT DOMAIN 83..131
FT /note="WAP 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00722"
FT REGION 85..131
FT /note="Elastase inhibitory domain"
FT SITE 98..99
FT /note="Reactive bond for chymotrypsin, trypsin and
FT elastase"
FT /evidence="ECO:0000250|UniProtKB:P03973"
FT DISULFID 36..65
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00722"
FT DISULFID 44..69
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00722"
FT DISULFID 52..64
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00722"
FT DISULFID 58..73
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00722"
FT DISULFID 90..119
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00722"
FT DISULFID 97..123
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00722"
FT DISULFID 106..118
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00722"
FT DISULFID 112..127
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00722"
FT MUTAGEN 39..40
FT /note="KK->DD: Loss of antimicrobial activity."
FT /evidence="ECO:0000269|PubMed:18322212"
FT MUTAGEN 92
FT /note="K->D: Loss of antimicrobial activity; when
FT associated with A-96."
FT /evidence="ECO:0000269|PubMed:18322212"
FT MUTAGEN 96
FT /note="R->D: Loss of antimicrobial activity; when
FT associated with A-92."
FT /evidence="ECO:0000269|PubMed:18322212"
SQ SEQUENCE 131 AA; 14308 MW; A57C9E30FE711B8F CRC64;
MKSCGLLPFT VLLALGILAP WTVEGGKNDA IKIGACPAKK PAQCLKLEKP QCRTDWECPG
KQRCCQDACG SKCVNPVPIR KPVWRKPGRC VKTQARCMML NPPNVCQRDG QCDGKYKCCE
GICGKVCLPP M
