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Protein

Antileukoproteinase

Gene

SLPI

Organism
Homo sapiens (Human)
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:3533531, PubMed:3462719, PubMed:2039600, PubMed:2110563, PubMed:10702419, PubMed:24121345). Modulates the inflammatory and immune responses after bacterial infection, and after infection by the intracellular parasite L.major. Down-regulates responses to bacterial lipopolysaccharide (LPS) (By similarity). Plays a role in regulating the activation of NF-kappa-B and inflammatory responses (PubMed:10702419, PubMed:24352879). Has antimicrobial activity against mycobacteria, but not against salmonella. Contributes to normal resistance against infection by M.tuberculosis. Required for normal resistance to infection by L.major. Required for normal wound healing, probably by preventing tissue damage by limiting protease activity (By similarity). Together with ELANE, required for normal differentiation and proliferation of bone marrow myeloid cells (PubMed:24352879).By similarityCurated7 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei97 – 982Reactive bond for chymotrypsin, trypsin and elastase3 Publications

GO - Molecular functioni

  • endopeptidase inhibitor activity Source: ProtInc
  • enzyme binding Source: UniProtKB
  • serine-type endopeptidase inhibitor activity Source: UniProtKB

GO - Biological processi

  • antibacterial humoral response Source: UniProtKB
  • immune response Source: UniProtKB
  • innate immune response Source: UniProtKB
  • negative regulation of protein binding Source: UniProtKB
  • negative regulation of viral genome replication Source: UniProtKB
  • 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):
BLPI
HUSI-12 Publications
Mucus proteinase inhibitor
Short name:
MPI
Protease inhibitor WAP4
Secretory leukocyte protease inhibitor1 Publication
Seminal proteinase inhibitor
WAP four-disulfide core domain protein 4
Gene namesi
Name:SLPI
Synonyms:WAP4, WFDC4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 20

Organism-specific databases

HGNCiHGNC:11092. SLPI.

Subcellular locationi

GO - Cellular componenti

  • extracellular exosome Source: UniProtKB
  • extracellular space Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi45 – 451R → G: No significant effect on inhibition of elastase, trypsin and chymotrypsin. 2 Publications
Mutagenesisi45 – 451R → M or V: No significant effect on inhibition of elastase, trypsin and chymotrypsin. 1 Publication
Mutagenesisi97 – 971L → F: Increases inhibition of chymotrypsin. 2 Publications
Mutagenesisi97 – 971L → G: Reduced inhibition of elastase. Strongly reduced inhibition of chymotrypsin and trypsin. 2 Publications
Mutagenesisi97 – 971L → K or R: Strongly reduced inhibition of elastase. Abolishes inhibition of trypsin. 2 Publications
Mutagenesisi98 – 981M → G: No significant effect on inhibition of elastase, trypsin and chymotrypsin. 1 Publication
Mutagenesisi99 – 991L → G: No significant effect on inhibition of elastase, trypsin and chymotrypsin. 1 Publication

Organism-specific databases

PharmGKBiPA35944.

Polymorphism and mutation databases

DMDMi113636.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 25254 PublicationsAdd
BLAST
Chaini26 – 132107AntileukoproteinasePRO_0000041355Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi35 ↔ 641 Publication
Disulfide bondi43 ↔ 681 Publication
Disulfide bondi51 ↔ 631 Publication
Disulfide bondi57 ↔ 721 Publication
Disulfide bondi89 ↔ 118Combined sources1 Publication
Disulfide bondi96 ↔ 122Combined sources1 Publication
Disulfide bondi105 ↔ 117Combined sources1 Publication
Disulfide bondi111 ↔ 126Combined sources1 Publication

Keywords - PTMi

Disulfide bond

Proteomic databases

MaxQBiP03973.
PaxDbiP03973.
PeptideAtlasiP03973.
PRIDEiP03973.

PTM databases

iPTMnetiP03973.
PhosphoSiteiP03973.

Miscellaneous databases

PMAP-CutDBP03973.

Expressioni

Tissue specificityi

Detected in blood plasma (PubMed:24352879). Detected in bone marrow myeloid cells (PubMed:24352879). Detected in airway sputum (PubMed:2039600). Detected in parotid gland secretions (PubMed:3462719). Detected in seminal plasma (at protein level) (PubMed:3485543). Detected in uterus cervix (PubMed:3533531).5 Publications

Inductioni

Down-regulated in response to low ELANE activity. Up-regulated by ELANE treatment in bone marrow cells.1 Publication

Gene expression databases

BgeeiENSG00000124107.
CleanExiHS_SLPI.
GenevisibleiP03973. HS.

Organism-specific databases

HPAiCAB002303.
HPA027774.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
FAM9BQ8IZU03EBI-355293,EBI-10175124
SGTAO437653EBI-355293,EBI-347996

GO - Molecular functioni

  • enzyme binding Source: UniProtKB

Protein-protein interaction databases

BioGridi112475. 5 interactions.
IntActiP03973. 5 interactions.
STRINGi9606.ENSP00000342082.

Structurei

Secondary structure

1
132
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi86 – 883Combined sources
Beta strandi95 – 973Combined sources
Helixi108 – 1103Combined sources
Beta strandi116 – 1205Combined sources
Beta strandi123 – 1275Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2Z7FX-ray1.70I83-132[»]
4DOQX-ray2.00B/D85-131[»]
ProteinModelPortaliP03973.
SMRiP03973. Positions 83-132.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP03973.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini28 – 7649WAP 1PROSITE-ProRule annotationAdd
BLAST
Domaini82 – 13049WAP 2PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni84 – 13249Elastase inhibitory domainAdd
BLAST

Sequence similaritiesi

Contains 2 WAP domains.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiENOG410J417. Eukaryota.
ENOG41116TS. LUCA.
GeneTreeiENSGT00730000111217.
HOGENOMiHOG000115819.
HOVERGENiHBG018073.
InParanoidiP03973.
OMAiSDWQCPG.
OrthoDBiEOG091G0S8U.
PhylomeDBiP03973.
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.

P03973-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKSSGLFPFL VLLALGTLAP WAVEGSGKSF KAGVCPPKKS AQCLRYKKPE
60 70 80 90 100
CQSDWQCPGK KRCCPDTCGI KCLDPVDTPN PTRRKPGKCP VTYGQCLMLN
110 120 130
PPNFCEMDGQ CKRDLKCCMG MCGKSCVSPV KA
Length:132
Mass (Da):14,326
Last modified:October 1, 1989 - v2
Checksum:iB62F3221E0903D90
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X04470 mRNA. Translation: CAA28158.1.
X04502 Genomic DNA. Translation: CAA28187.1.
X04503 mRNA. Translation: CAA28188.1.
AF114471 mRNA. Translation: AAD19661.1.
AK312192 mRNA. Translation: BAG35125.1.
AL035660 Genomic DNA. Translation: CAB64235.1.
CH471077 Genomic DNA. Translation: EAW75869.1.
BC020708 mRNA. Translation: AAH20708.1.
CCDSiCCDS13347.1.
PIRiA25541. TIHUSP.
RefSeqiNP_003055.1. NM_003064.3.
UniGeneiHs.517070.

Genome annotation databases

EnsembliENST00000338380; ENSP00000342082; ENSG00000124107.
GeneIDi6590.
KEGGihsa:6590.
UCSCiuc002xnm.2. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X04470 mRNA. Translation: CAA28158.1.
X04502 Genomic DNA. Translation: CAA28187.1.
X04503 mRNA. Translation: CAA28188.1.
AF114471 mRNA. Translation: AAD19661.1.
AK312192 mRNA. Translation: BAG35125.1.
AL035660 Genomic DNA. Translation: CAB64235.1.
CH471077 Genomic DNA. Translation: EAW75869.1.
BC020708 mRNA. Translation: AAH20708.1.
CCDSiCCDS13347.1.
PIRiA25541. TIHUSP.
RefSeqiNP_003055.1. NM_003064.3.
UniGeneiHs.517070.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2Z7FX-ray1.70I83-132[»]
4DOQX-ray2.00B/D85-131[»]
ProteinModelPortaliP03973.
SMRiP03973. Positions 83-132.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112475. 5 interactions.
IntActiP03973. 5 interactions.
STRINGi9606.ENSP00000342082.

Protein family/group databases

MEROPSiI17.001.

PTM databases

iPTMnetiP03973.
PhosphoSiteiP03973.

Polymorphism and mutation databases

DMDMi113636.

Proteomic databases

MaxQBiP03973.
PaxDbiP03973.
PeptideAtlasiP03973.
PRIDEiP03973.

Protocols and materials databases

DNASUi6590.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000338380; ENSP00000342082; ENSG00000124107.
GeneIDi6590.
KEGGihsa:6590.
UCSCiuc002xnm.2. human.

Organism-specific databases

CTDi6590.
GeneCardsiSLPI.
HGNCiHGNC:11092. SLPI.
HPAiCAB002303.
HPA027774.
MIMi107285. gene.
neXtProtiNX_P03973.
PharmGKBiPA35944.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410J417. Eukaryota.
ENOG41116TS. LUCA.
GeneTreeiENSGT00730000111217.
HOGENOMiHOG000115819.
HOVERGENiHBG018073.
InParanoidiP03973.
OMAiSDWQCPG.
OrthoDBiEOG091G0S8U.
PhylomeDBiP03973.
TreeFamiTF338375.

Miscellaneous databases

ChiTaRSiSLPI. human.
EvolutionaryTraceiP03973.
GeneWikiiSLPI.
GenomeRNAii6590.
PMAP-CutDBP03973.
PROiP03973.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000124107.
CleanExiHS_SLPI.
GenevisibleiP03973. HS.

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...

Entry informationi

Entry nameiSLPI_HUMAN
AccessioniPrimary (citable) accession number: P03973
Secondary accession number(s): B2R5H8, P07757
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 23, 1986
Last sequence update: October 1, 1989
Last modified: September 7, 2016
This is version 170 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

The pathologies of several chronic and acute diseases of the respiratory tract involve an imbalance between the proteases of cells involved in inflammatary responses and the inhibitors of these proteases. The inflammation-mediated release of neutrophil elastase in the lungs of patients whose levels of active alpha-1-antiprotease are compromised by genetic background, cigarette smoking, air pollutants, or a combination of all three can result in severe lung damage and a decreased lifespan. The relatively small size of this protein, its lack of glycosylation and its stability make this protein a candidate for use as a therapeutic agent in diseases mediated by leukocyte elastase-antielastase imbalances.Curated

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 20
    Human chromosome 20: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. 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.