P03973 (SLPI_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	SLPI
Synonyms:	WAP4, WFDC4

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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.
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.
Sequence similarities	Contains 2 WAP domains.

Ontologies

Keywords
Cellular component	Secreted
Domain	Repeat Signal
Molecular function	Protease inhibitor Serine protease inhibitor
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of protein binding Inferred from direct assay PubMed 19333378. Source: UniProtKB negative regulation of viral genome replication Inferred from direct assay PubMed 19333378. Source: UniProtKB
Cellular_component	extracellular region Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	endopeptidase inhibitor activity Traceable author statement Ref.8. Source: ProtInc 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

Ref.8 Ref.9 Ref.10

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

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

132

Helix Strand Turn

Details...

Beta strand

86 – 88

3

Beta strand

95 – 97

3

Helix

108 – 110

3

Beta strand

116 – 120

5

Beta strand

123 – 127

5

Sequences

	Sequence		Length	Mass (Da)
	P03973 [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] [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]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases 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).
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

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.

IPI

IPI00008580.

PIR

TIHUSP. A25541.

RefSeq

NP_003055.1. NM_003064.2.

UniGene

Hs.517070.

3D structure databases

PDBe
RCSB PDB
PDBj

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

ProteinModelPortal

P03973.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000342082.

Protein family/group databases

MEROPS

I17.001.

Polymorphism databases

DMDM

113636.

Proteomic databases

PaxDb

P03973.

PeptideAtlas

P03973.

PRIDE

P03973.

Protocols and materials databases

DNASU

6590.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000338380; ENSP00000342082; ENSG00000124107.

GeneID

6590.

KEGG

hsa:6590.

UCSC

uc002xnm.1. human.

Organism-specific databases

CTD

6590.

GeneCards

GC20M043880.

HGNC

HGNC:11092. SLPI.

HPA

CAB002303.
HPA027774.

MIM

107285. gene.

neXtProt

NX_P03973.

PharmGKB

PA35944.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG45457.

HOGENOM

HOG000115819.

HOVERGEN

HBG018073.

InParanoid

P03973.

OMA

SDWQCPG.

OrthoDB

EOG4BVRVX.

PhylomeDB

P03973.

Gene expression databases

ArrayExpress

P03973.

Bgee

P03973.

CleanEx

HS_SLPI.

Genevestigator

P03973.

GermOnline

ENSG00000124107. Homo sapiens.

Family and domain databases

Gene3D

4.10.75.10. 2 hits.

InterPro

IPR008197. WAP-type_4-diS_core.
[Graphical view]

Pfam

PF00095. WAP. 2 hits.
[Graphical view]

PRINTS

PR00003. 4DISULPHCORE.

SMART

SM00217. WAP. 2 hits.
[Graphical view]

SUPFAM

SSF57256. WAP. 2 hits.

PROSITE

PS51390. WAP. 2 hits.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

SLPI. human.

EvolutionaryTrace

P03973.

GenomeRNAi

6590.

NextBio

25637.

PMAP-CutDB

P03973.

SOURCE

Search...

Entry information

Entry name

SLPI_HUMAN

Accession

Primary (citable) accession number: P03973
Secondary accession number(s): B2R5H8, P07757

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 23, 1986
Last sequence update:	October 1, 1989
Last modified:	May 1, 2013
This is version 142 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.