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P03973

- SLPI_HUMAN

UniProt

P03973 - SLPI_HUMAN

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Protein

Antileukoproteinase

Gene
SLPI, WAP4, WFDC4
Organism
Homo sapiens (Human)
Status
Reviewed - 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. May prevent elastase-mediated damage to oral and possibly other mucosal tissues.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei45 – 462Reactive bond for trypsin Inferred
Sitei97 – 982Reactive bond for chymotrypsin and elastase Inferred

GO - Molecular functioni

  1. endopeptidase inhibitor activity Source: ProtInc
  2. enzyme binding Source: UniProtKB
  3. protein binding Source: UniProtKB
  4. serine-type endopeptidase inhibitor activity Source: UniProtKB-KW

GO - Biological processi

  1. negative regulation of endopeptidase activity Source: GOC
  2. negative regulation of protein binding Source: UniProtKB
  3. negative regulation of viral genome replication Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Protease inhibitor, Serine protease inhibitor

Protein family/group databases

MEROPSiI17.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Antileukoproteinase
Short name:
ALP
Alternative name(s):
BLPI
HUSI-1
Mucus proteinase inhibitor
Short name:
MPI
Protease inhibitor WAP4
Secretory leukocyte protease inhibitor
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
ProteomesiUP000005640: Chromosome 20

Organism-specific databases

HGNCiHGNC:11092. SLPI.

Subcellular locationi

GO - Cellular componenti

  1. extracellular vesicular exosome Source: UniProt
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA35944.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 25253 PublicationsAdd
BLAST
Chaini26 – 132107AntileukoproteinasePRO_0000041355Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi35 ↔ 64
Disulfide bondi43 ↔ 68
Disulfide bondi51 ↔ 63
Disulfide bondi57 ↔ 72
Disulfide bondi89 ↔ 118
Disulfide bondi96 ↔ 122
Disulfide bondi105 ↔ 117
Disulfide bondi111 ↔ 126

Keywords - PTMi

Disulfide bond

Proteomic databases

MaxQBiP03973.
PaxDbiP03973.
PeptideAtlasiP03973.
PRIDEiP03973.

Miscellaneous databases

PMAP-CutDBP03973.

Expressioni

Tissue specificityi

Mucous fluids.

Gene expression databases

ArrayExpressiP03973.
BgeeiP03973.
CleanExiHS_SLPI.
GenevestigatoriP03973.

Organism-specific databases

HPAiCAB002303.
HPA027774.

Interactioni

Protein-protein interaction databases

BioGridi112475. 2 interactions.
STRINGi9606.ENSP00000342082.

Structurei

Secondary structure

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

3D structure databases

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

Miscellaneous databases

EvolutionaryTraceiP03973.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini28 – 7649WAP 1Add
BLAST
Domaini82 – 13049WAP 2Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni26 – 8358Trypsin inhibitory domainAdd
BLAST
Regioni84 – 13249Elastase inhibitory domainAdd
BLAST

Sequence similaritiesi

Contains 2 WAP domains.

Keywords - Domaini

Repeat, Signal

Phylogenomic databases

eggNOGiNOG45457.
HOGENOMiHOG000115819.
HOVERGENiHBG018073.
InParanoidiP03973.
OMAiPWAVEGS.
OrthoDBiEOG7S7SG9.
PhylomeDBiP03973.
TreeFamiTF338375.

Family and domain databases

Gene3Di4.10.75.10. 2 hits.
InterProiIPR008197. WAP.
[Graphical view]
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

MKSSGLFPFL VLLALGTLAP WAVEGSGKSF KAGVCPPKKS AQCLRYKKPE    50
CQSDWQCPGK KRCCPDTCGI KCLDPVDTPN PTRRKPGKCP VTYGQCLMLN 100
PPNFCEMDGQ CKRDLKCCMG MCGKSCVSPV KA 132
Length:132
Mass (Da):14,326
Last modified:October 1, 1989 - v2
Checksum:iB62F3221E0903D90
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.1. human.

Polymorphism databases

DMDMi113636.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS13347.1.
PIRi A25541. TIHUSP.
RefSeqi NP_003055.1. NM_003064.3.
UniGenei Hs.517070.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2Z7F X-ray 1.70 I 83-132 [» ]
4DOQ X-ray 2.00 B/D 85-131 [» ]
ProteinModelPortali P03973.
SMRi P03973. Positions 83-132.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112475. 2 interactions.
STRINGi 9606.ENSP00000342082.

Protein family/group databases

MEROPSi I17.001.

Polymorphism databases

DMDMi 113636.

Proteomic databases

MaxQBi P03973.
PaxDbi P03973.
PeptideAtlasi P03973.
PRIDEi P03973.

Protocols and materials databases

DNASUi 6590.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000338380 ; ENSP00000342082 ; ENSG00000124107 .
GeneIDi 6590.
KEGGi hsa:6590.
UCSCi uc002xnm.1. human.

Organism-specific databases

CTDi 6590.
GeneCardsi GC20M043880.
HGNCi HGNC:11092. SLPI.
HPAi CAB002303.
HPA027774.
MIMi 107285. gene.
neXtProti NX_P03973.
PharmGKBi PA35944.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG45457.
HOGENOMi HOG000115819.
HOVERGENi HBG018073.
InParanoidi P03973.
OMAi PWAVEGS.
OrthoDBi EOG7S7SG9.
PhylomeDBi P03973.
TreeFami TF338375.

Miscellaneous databases

ChiTaRSi SLPI. human.
EvolutionaryTracei P03973.
GeneWikii SLPI.
GenomeRNAii 6590.
NextBioi 25637.
PMAP-CutDB P03973.
PROi P03973.
SOURCEi Search...

Gene expression databases

ArrayExpressi P03973.
Bgeei P03973.
CleanExi HS_SLPI.
Genevestigatori P03973.

Family and domain databases

Gene3Di 4.10.75.10. 2 hits.
InterProi IPR008197. WAP.
[Graphical view ]
Pfami PF00095. WAP. 2 hits.
[Graphical view ]
PRINTSi PR00003. 4DISULPHCORE.
SMARTi SM00217. WAP. 2 hits.
[Graphical view ]
SUPFAMi SSF57256. SSF57256. 2 hits.
PROSITEi PS51390. WAP. 2 hits.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Molecular cloning and expression of cDNA for human antileukoprotease from cervix uterus."
    Heinzel R., Appelhans H., Gassen G., Seemueller U., Machleidt W., Fritz H., Steffens G.
    Eur. J. Biochem. 160:61-67(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Cervix.
  2. "Isolation and sequence of a human gene encoding a potent inhibitor of leukocyte proteases."
    Stetler G., Brewer M.T., Thompson R.C.
    Nucleic Acids Res. 14:7883-7896(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
    Tissue: Parotid gland.
  3. "Cloning and characterization of SLPI from human intestinal epithelium."
    Si-Tahar M., Merlin D., Sitaraman S., Madara J.L.
    Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Intestine.
  4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Tongue.
  5. "The DNA sequence and comparative analysis of human chromosome 20."
    Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E.
    , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
    Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  7. "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: Liver.
  8. "The acid-stable proteinase inhibitor of human mucous secretions (HUSI-I, antileukoprotease). Complete amino acid sequence as revealed by protein and cDNA sequencing and structural homology to whey proteins and Red sea turtle proteinase inhibitor."
    Seemueller U., Arnhold M., Fritz H., Wiedenmann K., Machleidt W., Heinzel R., Appelhans H., Gassen H.-G., Lottspeich F.
    FEBS Lett. 199:43-48(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 26-132, NUCLEOTIDE SEQUENCE OF 26-65.
  9. "Isolation, properties, and complete amino acid sequence of human secretory leukocyte protease inhibitor, a potent inhibitor of leukocyte elastase."
    Thompson R.C., Ohlsson K.
    Proc. Natl. Acad. Sci. U.S.A. 83:6692-6696(1986) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 26-132.
  10. "Purification and characterization of elastase-specific inhibitor. Sequence homology with mucus proteinase inhibitor."
    Sallenave J.-M., Ryle A.P.
    Biol. Chem. Hoppe-Seyler 372:13-21(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 26-52.
  11. "The 2.5 A X-ray crystal structure of the acid-stable proteinase inhibitor from human mucous secretions analysed in its complex with bovine alpha-chymotrypsin."
    Gruetter M.G., Fendrich G., Huber R., Bode W.
    EMBO J. 7:345-351(1988) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).

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 3, 2014
This is version 153 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.

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

External Data

Dasty 3

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