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Protein

Antileukoproteinase

Gene

Slpi

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Acid-stable proteinase inhibitor with strong affinities for trypsin, chymotrypsin, elastase, and cathepsin G (PubMed:9126337). Modulates the innate immune response after bacterial infection (PubMed:12615907). Contributes to regulate the inflammatory and immune responses to the intracellular parasite L.major (PubMed:25030421). Down-regulates responses to bacterial lipopolysaccharide (LPS) (PubMed:9039268, PubMed:12615907, PubMed:25030421). Plays a role in regulating the activation of NF-kappa-B and inflammatory responses (PubMed:11017147, PubMed:12615907). Has antimicrobial activity against mycobacteria, but not against salmonella (PubMed:18322212). Contributes to normal resistance against infection by M.tuberculosis (PubMed:18322212). Required for normal resistance to L.major (PubMed:25030421). Required for normal wound healing, probably by preventing tissue damage by limiting protease activity (PubMed:11017147, PubMed:25030421). Together with ELANE, required for normal differentiation and proliferation of bone marrow myeloid cells (By similarity).By similarityCurated7 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei98 – 992Reactive bond for chymotrypsin, trypsin and elastaseBy similarity

GO - Molecular functioni

GO - Biological processi

  • antibacterial humoral response Source: UniProtKB
  • immune response Source: UniProtKB
  • innate immune response Source: UniProtKB
  • negative regulation of protein binding Source: MGI
  • negative regulation of viral genome replication Source: MGI
  • response to lipopolysaccharide Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Antibiotic, Antimicrobial, Protease inhibitor, Serine protease inhibitor

Keywords - Biological processi

Immunity, Innate immunity

Protein family/group databases

MEROPSiI17.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Antileukoproteinase
Short name:
ALP
Alternative name(s):
Secretory leukocyte protease inhibitor1 Publication
Gene namesi
Name:Slpi
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:109297. Slpi.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: MGI
  • extracellular matrix Source: Ensembl
  • extracellular space Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Disruption phenotypei

Mutant mice show delayed epithelial wound healing and an increased inflammatory response at the site of wounding, possibly due to increased elastase activity (PubMed:11017147, PubMed:25030421). Mutant mice show an increased tendency to die from toxic shock after exposure to bacterial lipopolysaccharide (LPS) (PubMed:12615907). Mutant mice are highly susceptible to M.tuberculosis; all die within 50 days after infection (PubMed:18322212). Mutant mice are highly susceptible infection by L.major. Contrary to what is observed with wild-type, the parasites are not restricted to the initial site of infection, but spread to spleen, liver and bone morrow. The skin lesions at the initial site of infection do not heal normally, but become bigger over time, in parallel with the spread of the parasites. The inflammatory response at the site of infection is more intense and persists longer than normal. Increased protease activity is observed in these lesions and may be the cause of the extensive tissue damage and necrosis (PubMed:25030421).4 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi39 – 402KK → DD: Loss of antimicrobial activity. 1 Publication
Mutagenesisi92 – 921K → D: Loss of antimicrobial activity; when associated with A-96. 1 Publication
Mutagenesisi96 – 961R → D: Loss of antimicrobial activity; when associated with A-92. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 25251 PublicationAdd
BLAST
Chaini26 – 131106AntileukoproteinasePRO_0000041356Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi36 ↔ 65PROSITE-ProRule annotation
Disulfide bondi44 ↔ 69PROSITE-ProRule annotation
Disulfide bondi52 ↔ 64PROSITE-ProRule annotation
Disulfide bondi58 ↔ 73PROSITE-ProRule annotation
Disulfide bondi90 ↔ 119PROSITE-ProRule annotation
Disulfide bondi97 ↔ 123PROSITE-ProRule annotation
Disulfide bondi106 ↔ 118PROSITE-ProRule annotation
Disulfide bondi112 ↔ 127PROSITE-ProRule annotation

Keywords - PTMi

Disulfide bond

Proteomic databases

PaxDbiP97430.
PRIDEiP97430.

Expressioni

Tissue specificityi

Detected in bronchial epithelial cells (PubMed:18322212). Detected in bronchoalveolar fluid after infection with M.tuberculosis (at protein level) (PubMed:18322212). Highest expression in lung, spleen, intestine and epididymis with lower levels in liver and seminal vesicle. No expression in brain, heart, kidney and muscle.4 Publications

Inductioni

Up-regulated by bacterial lipopolysaccharide (PubMed:9039268, PubMed:25030421). Up-regulated in lung after infection with M.tuberculosis (PubMed:18322212). Down-regulated by IFNG (PubMed:9039268). Up-regulated in lung in response to bacterial pneumonia (PubMed:9351627). Up-regulated in macrophages after exposure to L.major (PubMed:25030421). Not up-regulated in spleen in response to bacterial pneumonia (PubMed:9351627). Up-regulated in wounded skin (PubMed:11017147).5 Publications

Gene expression databases

BgeeiP97430.
CleanExiMM_SLPI.
ExpressionAtlasiP97430. baseline and differential.
GenevisibleiP97430. MM.

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi203333. 1 interaction.
STRINGi10090.ENSMUSP00000104992.

Structurei

3D structure databases

ProteinModelPortaliP97430.
SMRiP97430. Positions 85-131.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini29 – 7749WAP 1PROSITE-ProRule annotationAdd
BLAST
Domaini83 – 13149WAP 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni85 – 13147Elastase inhibitory domainAdd
BLAST

Sequence similaritiesi

Contains 2 WAP domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410J417. Eukaryota.
ENOG41116TS. LUCA.
HOGENOMiHOG000115819.
HOVERGENiHBG018073.
InParanoidiP97430.
OMAiRCIWHEK.
OrthoDBiEOG7S7SG9.
PhylomeDBiP97430.
TreeFamiTF338375.

Family and domain databases

Gene3Di4.10.75.10. 2 hits.
InterProiIPR029712. ALP.
IPR008197. WAP_dom.
[Graphical view]
PANTHERiPTHR19441:SF44. PTHR19441:SF44. 1 hit.
PfamiPF00095. WAP. 2 hits.
[Graphical view]
PRINTSiPR00003. 4DISULPHCORE.
SMARTiSM00217. WAP. 2 hits.
[Graphical view]
SUPFAMiSSF57256. SSF57256. 2 hits.
PROSITEiPS51390. WAP. 2 hits.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P97430-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKSCGLLPFT VLLALGILAP WTVEGGKNDA IKIGACPAKK PAQCLKLEKP
60 70 80 90 100
QCRTDWECPG KQRCCQDACG SKCVNPVPIR KPVWRKPGRC VKTQARCMML
110 120 130
NPPNVCQRDG QCDGKYKCCE GICGKVCLPP M
Length:131
Mass (Da):14,308
Last modified:May 1, 1997 - v1
Checksum:iA57C9E30FE711B8F
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U73004 mRNA. Translation: AAC53047.1.
U88093 mRNA. Translation: AAC53140.1.
U94341 mRNA. Translation: AAC53394.1.
BC028509 mRNA. Translation: AAH28509.1.
CCDSiCCDS17033.1.
RefSeqiNP_035544.1. NM_011414.3.
UniGeneiMm.371583.

Genome annotation databases

EnsembliENSMUST00000109367; ENSMUSP00000104992; ENSMUSG00000017002.
GeneIDi20568.
KEGGimmu:20568.
UCSCiuc008nuj.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U73004 mRNA. Translation: AAC53047.1.
U88093 mRNA. Translation: AAC53140.1.
U94341 mRNA. Translation: AAC53394.1.
BC028509 mRNA. Translation: AAH28509.1.
CCDSiCCDS17033.1.
RefSeqiNP_035544.1. NM_011414.3.
UniGeneiMm.371583.

3D structure databases

ProteinModelPortaliP97430.
SMRiP97430. Positions 85-131.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi203333. 1 interaction.
STRINGi10090.ENSMUSP00000104992.

Protein family/group databases

MEROPSiI17.001.

Proteomic databases

PaxDbiP97430.
PRIDEiP97430.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000109367; ENSMUSP00000104992; ENSMUSG00000017002.
GeneIDi20568.
KEGGimmu:20568.
UCSCiuc008nuj.1. mouse.

Organism-specific databases

CTDi6590.
MGIiMGI:109297. Slpi.

Phylogenomic databases

eggNOGiENOG410J417. Eukaryota.
ENOG41116TS. LUCA.
HOGENOMiHOG000115819.
HOVERGENiHBG018073.
InParanoidiP97430.
OMAiRCIWHEK.
OrthoDBiEOG7S7SG9.
PhylomeDBiP97430.
TreeFamiTF338375.

Miscellaneous databases

PROiP97430.
SOURCEiSearch...

Gene expression databases

BgeeiP97430.
CleanExiMM_SLPI.
ExpressionAtlasiP97430. baseline and differential.
GenevisibleiP97430. MM.

Family and domain databases

Gene3Di4.10.75.10. 2 hits.
InterProiIPR029712. ALP.
IPR008197. WAP_dom.
[Graphical view]
PANTHERiPTHR19441:SF44. PTHR19441:SF44. 1 hit.
PfamiPF00095. WAP. 2 hits.
[Graphical view]
PRINTSiPR00003. 4DISULPHCORE.
SMARTiSM00217. WAP. 2 hits.
[Graphical view]
SUPFAMiSSF57256. SSF57256. 2 hits.
PROSITEiPS51390. WAP. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Secretory leukocyte protease inhibitor: a macrophage product induced by and antagonistic to bacterial lipopolysaccharide."
    Jin F.-Y., Nathan C.F., Radzioch D., Ding A.
    Cell 88:417-426(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INDUCTION BY BACTERIAL LIPOPOLYSACCHARIDE, TISSUE SPECIFICITY.
  2. "The cloning and characterization of a murine secretory leukocyte protease inhibitor cDNA."
    Zitnik R.J., Zhang J., Kashem M.A., Kohno T., Lyons D.E., Wright C.D., Rosen E., Goldberg I., Hayday A.C.
    Biochem. Biophys. Res. Commun. 232:687-697(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 26-51, FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  3. "Bacterial pneumonia causes augmented expression of the secretory leukoprotease inhibitor gene in the murine lung."
    Abe T., Tominaga Y., Kikuchi T., Watanabe A., Satoh K., Watanabe Y., Nukiwa T.
    Am. J. Respir. Crit. Care Med. 156:1235-1240(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, INDUCTION BY PNEUMONIA.
    Strain: C57BL/6 X CBA.
    Tissue: Lung.
  4. "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: Mammary gland.
  5. "Secretory leukocyte protease inhibitor mediates non-redundant functions necessary for normal wound healing."
    Ashcroft G.S., Lei K., Jin W., Longenecker G., Kulkarni A.B., Greenwell-Wild T., Hale-Donze H., McGrady G., Song X.Y., Wahl S.M.
    Nat. Med. 6:1147-1153(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION, INDUCTION BY WOUNDING.
  6. "Increased susceptibility to LPS-induced endotoxin shock in secretory leukoprotease inhibitor (SLPI)-deficient mice."
    Nakamura A., Mori Y., Hagiwara K., Suzuki T., Sakakibara T., Kikuchi T., Igarashi T., Ebina M., Abe T., Miyazaki J., Takai T., Nukiwa T.
    J. Exp. Med. 197:669-674(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION.
  7. Cited for: DISRUPTION PHENOTYPE, FUNCTION, TISSUE SPECIFICITY, SUBCELLULAR LOCATION, MUTAGENESIS OF 39-LYS-LYS-40; LYS-92 AND ARG-96.
  8. "Aberrant host defense against Leishmania major in the absence of SLPI."
    McCartney-Francis N., Jin W., Belkaid Y., McGrady G., Wahl S.M.
    J. Leukoc. Biol. 96:917-929(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE, FUNCTION, INDUCTION.

Entry informationi

Entry nameiSLPI_MOUSE
AccessioniPrimary (citable) accession number: P97430
Secondary accession number(s): O09081, O09082
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: May 1, 1997
Last modified: June 8, 2016
This is version 127 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.