Reviewed, UniProtKB/Swiss-Prot P03973 (SLPI_HUMAN)

Names and origin

Protein names

Recommended name:
    Antileukoproteinase
      Short name=ALP
Alternative name(s):
    Secretory leukocyte protease inhibitor
    HUSI-1
    Seminal proteinase inhibitor
    BLPI
    Mucus proteinase inhibitor
      Short name=MPI
    WAP four-disulfide core domain protein 4
    Protease inhibitor WAP4

Gene names

Name:	SLPI
Synonyms:	WAP4, WFDC4

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	132 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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.
Subcellular location	Secreted.
Tissue specificity	Mucous fluids.
Involvement in disease	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.
Sequence similarities	Contains 2 WAP domains.

Ontologies

Keywords
Cellular component	Secreted
Domain	Repeat Signal
Molecular function	Protease inhibitor Serine protease inhibitor
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Cellular component	extracellular region Inferred from electronic annotation. Source: InterPro
Molecular function	serine-type endopeptidase inhibitor activity Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 25	25
	Chain	26 – 132	107	Antileukoproteinase		PRO_0000041355
Regions
	Domain	28 – 76	49	WAP 1
	Domain	82 – 130	49	WAP 2
	Region	26 – 83	58	Trypsin inhibitory domain
	Region	84 – 132	49	Elastase inhibitory domain
Sites
	Site	45 – 46	2	Reactive bond for trypsin Probable
	Site	97 – 98	2	Reactive bond for chymotrypsin and elastase Probable
Amino acid modifications
	Disulfide bond	35 ↔ 64
	Disulfide bond	43 ↔ 68
	Disulfide bond	51 ↔ 63
	Disulfide bond	57 ↔ 72
	Disulfide bond	89 ↔ 118
	Disulfide bond	96 ↔ 122
	Disulfide bond	105 ↔ 117
	Disulfide bond	111 ↔ 126

Sequences

	Sequence		Length	Mass (Da)
	P03973-1 [UniParc]. Last modified October 1, 1989. Version 2. Checksum: B62F3221E0903D90	FASTA	132	14,326
	10 20 30 40 50 60 MKSSGLFPFL VLLALGTLAP WAVEGSGKSF KAGVCPPKKS AQCLRYKKPE CQSDWQCPGK 70 80 90 100 110 120 KRCCPDTCGI KCLDPVDTPN PTRRKPGKCP VTYGQCLMLN PPNFCEMDGQ CKRDLKCCMG 130 MCGKSCVSPV KA

References

	« Hide 'large scale' referencesShow 'large scale' references »
[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: 3533531] [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: 3640338] [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]	"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: 11780052] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Liver.
[6]	"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: 3485543] [Abstract] Cited for: PROTEIN SEQUENCE OF 26-132, NUCLEOTIDE SEQUENCE OF 26-65.
[7]	"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: 3462719] [Abstract] Cited for: PROTEIN SEQUENCE OF 26-132.
[8]	"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: 2039600] [Abstract] Cited for: PROTEIN SEQUENCE OF 26-52.
[9]	"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: 3366116] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

X04470 mRNA. Translation: CAA28158.1.
X04502 Genomic DNA. Translation: CAA28187.1.
X04503 mRNA. Translation: CAA28188.1.
AF114471 mRNA. Translation: AAD19661.1.
AL035660 Genomic DNA. Translation: CAB64235.1.
BC020708 mRNA. Translation: AAH20708.1.

PIR

TIHUSP. A25541.

RefSeq

NP_003055.1.

UniGene

Hs.517070

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2Z7F	X-ray	1.70	I	83-132	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P03973.

Protein family/group databases

MEROPS

I17.001.
I17.950.

Proteomic databases

PeptideAtlas

P03973.

Genome annotation databases

Ensembl

ENSG00000124107. Homo sapiens. [Contig view]

GeneID

6590.

KEGG

hsa:6590.

Organism-specific databases

H-InvDB

HIX0015854.

HGNC

HGNC:11092. SLPI.

HPA

CAB002303.

MIM

107285. gene.

PharmGKB

PA35944.

GenAtlas

Search...

GeneCards

Search...

Phylogenomic databases

HOVERGEN

P03973.

Gene expression databases

ArrayExpress

P03973.

CleanEx

HS_SLPI.

GermOnline

ENSG00000124107. Homo sapiens.

Family and domain databases

InterPro

IPR015874. 4-disulphide_core.
IPR008197. Whey_acidic_protein_4-diS_core.
[Graphical view]

Gene3D

G3DSA:4.10.75.10. Whey_acidic_protein_4-diS_core. 2 hits.

Pfam

PF00095. WAP. 2 hits.
[Graphical view]

PRINTS

PR00003. 4DISULPHCORE.

ProDom

PD001224. Prot_inh_I17. 1 hit.
[Graphical view] [Entries sharing at least one domain]

SMART

SM00217. WAP. 2 hits.
[Graphical view]

PROSITE

PS51390. WAP. 2 hits.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

25637.

SOURCE

Search...

Entry information

Entry name

SLPI_HUMAN

Accession

Primary (citable) accession number: P03973
Secondary accession number(s): P07757

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 23, 1986
Last sequence update:	October 1, 1989
Last modified:	November 25, 2008
This is version 102 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)