SLPI_HUMAN
ID SLPI_HUMAN Reviewed; 132 AA.
AC P03973; B2R5H8; P07757;
DT 23-OCT-1986, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1989, sequence version 2.
DT 03-AUG-2022, entry version 210.
DE RecName: Full=Antileukoproteinase;
DE Short=ALP;
DE AltName: Full=BLPI;
DE AltName: Full=HUSI-1 {ECO:0000303|PubMed:3485543, ECO:0000303|PubMed:3533531};
DE AltName: Full=Mucus proteinase inhibitor;
DE Short=MPI;
DE AltName: Full=Protease inhibitor WAP4;
DE AltName: Full=Secretory leukocyte protease inhibitor {ECO:0000303|PubMed:3462719};
DE AltName: Full=Seminal proteinase inhibitor;
DE AltName: Full=WAP four-disulfide core domain protein 4;
DE Flags: Precursor;
GN Name=SLPI; Synonyms=WAP4, WFDC4;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC TISSUE=Cervix;
RX PubMed=3533531; DOI=10.1111/j.1432-1033.1986.tb09940.x;
RA Heinzel R., Appelhans H., Gassen G., Seemueller U., Machleidt W., Fritz H.,
RA Steffens G.;
RT "Molecular cloning and expression of cDNA for human antileukoprotease from
RT cervix uterus.";
RL Eur. J. Biochem. 160:61-67(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC TISSUE=Parotid gland;
RX PubMed=3640338; DOI=10.1093/nar/14.20.7883;
RA Stetler G., Brewer M.T., Thompson R.C.;
RT "Isolation and sequence of a human gene encoding a potent inhibitor of
RT leukocyte proteases.";
RL Nucleic Acids Res. 14:7883-7896(1986).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Intestine;
RA Si-Tahar M., Merlin D., Sitaraman S., Madara J.L.;
RT "Cloning and characterization of SLPI from human intestinal epithelium.";
RL Submitted (DEC-1998) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Tongue;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP PROTEIN SEQUENCE OF 26-132, NUCLEOTIDE SEQUENCE [MRNA] OF 26-65,
RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=3485543; DOI=10.1016/0014-5793(86)81220-0;
RA Seemueller U., Arnhold M., Fritz H., Wiedenmann K., Machleidt W.,
RA Heinzel R., Appelhans H., Gassen H.-G., Lottspeich F.;
RT "The acid-stable proteinase inhibitor of human mucous secretions (HUSI-I,
RT antileukoprotease). Complete amino acid sequence as revealed by protein and
RT cDNA sequencing and structural homology to whey proteins and Red sea turtle
RT proteinase inhibitor.";
RL FEBS Lett. 199:43-48(1986).
RN [9]
RP PROTEIN SEQUENCE OF 26-132, FUNCTION, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=3462719; DOI=10.1073/pnas.83.18.6692;
RA Thompson R.C., Ohlsson K.;
RT "Isolation, properties, and complete amino acid sequence of human secretory
RT leukocyte protease inhibitor, a potent inhibitor of leukocyte elastase.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:6692-6696(1986).
RN [10]
RP PROTEIN SEQUENCE OF 26-52, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND
RP FUNCTION.
RX PubMed=2039600; DOI=10.1515/bchm3.1991.372.1.13;
RA Sallenave J.-M., Ryle A.P.;
RT "Purification and characterization of elastase-specific inhibitor. Sequence
RT homology with mucus proteinase inhibitor.";
RL Biol. Chem. Hoppe-Seyler 372:13-21(1991).
RN [11]
RP PROTEIN SEQUENCE OF 26-46 AND 94-132, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC TISSUE=Tear;
RX PubMed=25946035; DOI=10.1021/acs.jproteome.5b00179;
RA Azkargorta M., Soria J., Ojeda C., Guzman F., Acera A., Iloro I.,
RA Suarez T., Elortza F.;
RT "Human basal tear peptidome characterization by CID, HCD, and ETD followed
RT by in silico and in vitro analyses for antimicrobial peptide
RT identification.";
RL J. Proteome Res. 14:2649-2658(2015).
RN [12]
RP FUNCTION, AND MUTAGENESIS OF ARG-45; LEU-97; MET-98 AND LEU-99.
RX PubMed=2110563; DOI=10.1016/s0021-9258(19)39026-x;
RA Eisenberg S.P., Hale K.K., Heimdal P., Thompson R.C.;
RT "Location of the protease-inhibitory region of secretory leukocyte protease
RT inhibitor.";
RL J. Biol. Chem. 265:7976-7981(1990).
RN [13]
RP FUNCTION, AND MUTAGENESIS OF ARG-45 AND LEU-97.
RX PubMed=10702419; DOI=10.1016/s0002-9440(10)64971-1;
RA Mulligan M.S., Lentsch A.B., Huber-Lang M., Guo R.F., Sarma V.,
RA Wright C.D., Ulich T.R., Ward P.A.;
RT "Anti-inflammatory effects of mutant forms of secretory leukocyte protease
RT inhibitor.";
RL Am. J. Pathol. 156:1033-1039(2000).
RN [14]
RP INTERACTION WITH GRN.
RX PubMed=12526812; DOI=10.1016/s0092-8674(02)01141-8;
RA Zhu J., Nathan C., Jin W., Sim D., Ashcroft G.S., Wahl S.M., Lacomis L.,
RA Erdjument-Bromage H., Tempst P., Wright C.D., Ding A.;
RT "Conversion of proepithelin to epithelins: roles of SLPI and elastase in
RT host defense and wound repair.";
RL Cell 111:867-878(2002).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, INDUCTION BY ELANE, AND TISSUE SPECIFICITY.
RX PubMed=24352879; DOI=10.1182/blood-2013-06-508887;
RA Klimenkova O., Ellerbeck W., Klimiankou M., Unalan M., Kandabarau S.,
RA Gigina A., Hussein K., Zeidler C., Welte K., Skokowa J.;
RT "A lack of secretory leukocyte protease inhibitor (SLPI) causes defects in
RT granulocytic differentiation.";
RL Blood 123:1239-1249(2014).
RN [16]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH CHYMOTRYPSIN,
RP DISULFIDE BONDS, AND REACTIVE BOND.
RX PubMed=3366116; DOI=10.1002/j.1460-2075.1988.tb02819.x;
RA Gruetter M.G., Fendrich G., Huber R., Bode W.;
RT "The 2.5 A X-ray crystal structure of the acid-stable proteinase inhibitor
RT from human mucous secretions analysed in its complex with bovine alpha-
RT chymotrypsin.";
RL EMBO J. 7:345-351(1988).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 83-132 IN COMPLEX WITH ELANE,
RP REACTIVE BOND, AND DISULFIDE BONDS.
RX PubMed=18421166; DOI=10.1107/s0909049507060670;
RA Koizumi M., Fujino A., Fukushima K., Kamimura T., Takimoto-Kamimura M.;
RT "Complex of human neutrophil elastase with 1/2SLPI.";
RL J. Synchrotron Radiat. 15:308-311(2008).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 85-131 IN COMPLEX WITH TRYPSIN,
RP FUNCTION, REACTIVE BOND, AND DISULFIDE BONDS.
RX PubMed=24121345; DOI=10.1107/s090904951302133x;
RA Fukushima K., Kamimura T., Takimoto-Kamimura M.;
RT "Structure basis 1/2SLPI and porcine pancreas trypsin interaction.";
RL J. Synchrotron Radiat. 20:943-947(2013).
CC -!- FUNCTION: Acid-stable proteinase inhibitor with strong affinities for
CC trypsin, chymotrypsin, elastase, and cathepsin G (PubMed:3533531,
CC PubMed:3462719, PubMed:2039600, PubMed:2110563, PubMed:10702419,
CC PubMed:24121345). Modulates the inflammatory and immune responses after
CC bacterial infection, and after infection by the intracellular parasite
CC L.major. Down-regulates responses to bacterial lipopolysaccharide (LPS)
CC (By similarity). Plays a role in regulating the activation of NF-kappa-
CC B and inflammatory responses (PubMed:10702419, PubMed:24352879). Has
CC antimicrobial activity against mycobacteria, but not against
CC salmonella. Contributes to normal resistance against infection by
CC M.tuberculosis. Required for normal resistance to infection by L.major.
CC Required for normal wound healing, probably by preventing tissue damage
CC by limiting protease activity (By similarity). Together with ELANE,
CC required for normal differentiation and proliferation of bone marrow
CC myeloid cells (PubMed:24352879). {ECO:0000250|UniProtKB:P97430,
CC ECO:0000269|PubMed:10702419, ECO:0000269|PubMed:2039600,
CC ECO:0000269|PubMed:2110563, ECO:0000269|PubMed:24121345,
CC ECO:0000269|PubMed:24352879, ECO:0000269|PubMed:3462719,
CC ECO:0000269|PubMed:3533531, ECO:0000305}.
CC -!- SUBUNIT: Interacts with GRN; interaction protects progranulin from
CC proteolysis. {ECO:0000269|PubMed:12526812}.
CC -!- INTERACTION:
CC P03973; Q9BXU9: CALN1; NbExp=3; IntAct=EBI-355293, EBI-12187137;
CC P03973; Q96Q77: CIB3; NbExp=3; IntAct=EBI-355293, EBI-10292696;
CC P03973; Q12805: EFEMP1; NbExp=3; IntAct=EBI-355293, EBI-536772;
CC P03973; Q8IZU0: FAM9B; NbExp=6; IntAct=EBI-355293, EBI-10175124;
CC P03973; P49639: HOXA1; NbExp=3; IntAct=EBI-355293, EBI-740785;
CC P03973; O43561-2: LAT; NbExp=3; IntAct=EBI-355293, EBI-8070286;
CC P03973; Q13064: MKRN3; NbExp=3; IntAct=EBI-355293, EBI-2340269;
CC P03973; P41271-2: NBL1; NbExp=3; IntAct=EBI-355293, EBI-12135485;
CC P03973; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-355293, EBI-741158;
CC P03973; Q8WWB5: PIH1D2; NbExp=3; IntAct=EBI-355293, EBI-10232538;
CC P03973; O43765: SGTA; NbExp=6; IntAct=EBI-355293, EBI-347996;
CC P03973; Q96EQ0: SGTB; NbExp=3; IntAct=EBI-355293, EBI-744081;
CC P03973; Q96QK8: SMIM14; NbExp=3; IntAct=EBI-355293, EBI-373430;
CC P03973; Q9UMX0: UBQLN1; NbExp=5; IntAct=EBI-355293, EBI-741480;
CC P03973; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-355293, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2039600,
CC ECO:0000269|PubMed:24352879, ECO:0000269|PubMed:3462719,
CC ECO:0000269|PubMed:3485543}.
CC -!- TISSUE SPECIFICITY: Detected in blood plasma (PubMed:24352879).
CC Detected in bone marrow myeloid cells (PubMed:24352879). Detected in
CC airway sputum (PubMed:2039600). Detected in parotid gland secretions
CC (PubMed:3462719). Detected in seminal plasma (at protein level)
CC (PubMed:3485543). Detected in uterus cervix (PubMed:3533531).
CC {ECO:0000269|PubMed:2039600, ECO:0000269|PubMed:24352879,
CC ECO:0000269|PubMed:3462719, ECO:0000269|PubMed:3485543,
CC ECO:0000269|PubMed:3533531}.
CC -!- INDUCTION: Down-regulated in response to low ELANE activity. Up-
CC regulated by ELANE treatment in bone marrow cells.
CC {ECO:0000269|PubMed:24352879}.
CC -!- MISCELLANEOUS: The pathologies of several chronic and acute diseases of
CC the respiratory tract involve an imbalance between the proteases of
CC cells involved in inflammatory responses and the inhibitors of these
CC proteases. The inflammation-mediated release of neutrophil elastase in
CC the lungs of patients whose levels of active alpha-1-antiprotease are
CC compromised by genetic background, cigarette smoking, air pollutants,
CC or a combination of all three can result in severe lung damage and a
CC decreased lifespan. The relatively small size of this protein, its lack
CC of glycosylation and its stability make this protein a candidate for
CC use as a therapeutic agent in diseases mediated by leukocyte elastase-
CC antielastase imbalances. {ECO:0000305}.
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DR EMBL; X04470; CAA28158.1; -; mRNA.
DR EMBL; X04502; CAA28187.1; -; Genomic_DNA.
DR EMBL; X04503; CAA28188.1; -; mRNA.
DR EMBL; AF114471; AAD19661.1; -; mRNA.
DR EMBL; AK312192; BAG35125.1; -; mRNA.
DR EMBL; AL035660; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW75869.1; -; Genomic_DNA.
DR EMBL; BC020708; AAH20708.1; -; mRNA.
DR CCDS; CCDS13347.1; -.
DR PIR; A25541; TIHUSP.
DR RefSeq; NP_003055.1; NM_003064.3.
DR PDB; 2Z7F; X-ray; 1.70 A; I=83-132.
DR PDB; 4DOQ; X-ray; 2.00 A; B/D=85-131.
DR PDBsum; 2Z7F; -.
DR PDBsum; 4DOQ; -.
DR AlphaFoldDB; P03973; -.
DR SMR; P03973; -.
DR BioGRID; 112475; 25.
DR IntAct; P03973; 20.
DR MINT; P03973; -.
DR STRING; 9606.ENSP00000342082; -.
DR MEROPS; I17.001; -.
DR MEROPS; I17.950; -.
DR iPTMnet; P03973; -.
DR PhosphoSitePlus; P03973; -.
DR BioMuta; SLPI; -.
DR DMDM; 113636; -.
DR EPD; P03973; -.
DR jPOST; P03973; -.
DR MassIVE; P03973; -.
DR MaxQB; P03973; -.
DR PaxDb; P03973; -.
DR PeptideAtlas; P03973; -.
DR PRIDE; P03973; -.
DR ProteomicsDB; 51625; -.
DR Antibodypedia; 3705; 416 antibodies from 36 providers.
DR DNASU; 6590; -.
DR Ensembl; ENST00000338380.2; ENSP00000342082.2; ENSG00000124107.5.
DR GeneID; 6590; -.
DR KEGG; hsa:6590; -.
DR MANE-Select; ENST00000338380.2; ENSP00000342082.2; NM_003064.4; NP_003055.1.
DR UCSC; uc002xnm.2; human.
DR CTD; 6590; -.
DR DisGeNET; 6590; -.
DR GeneCards; SLPI; -.
DR HGNC; HGNC:11092; SLPI.
DR HPA; ENSG00000124107; Group enriched (cervix, salivary gland).
DR MIM; 107285; gene.
DR neXtProt; NX_P03973; -.
DR OpenTargets; ENSG00000124107; -.
DR PharmGKB; PA35944; -.
DR VEuPathDB; HostDB:ENSG00000124107; -.
DR eggNOG; ENOG502SWIR; Eukaryota.
DR GeneTree; ENSGT00730000111217; -.
DR HOGENOM; CLU_105901_2_1_1; -.
DR InParanoid; P03973; -.
DR OMA; CPVVYGQ; -.
DR OrthoDB; 1560605at2759; -.
DR PhylomeDB; P03973; -.
DR TreeFam; TF338375; -.
DR PathwayCommons; P03973; -.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; P03973; -.
DR BioGRID-ORCS; 6590; 16 hits in 1066 CRISPR screens.
DR ChiTaRS; SLPI; human.
DR EvolutionaryTrace; P03973; -.
DR GeneWiki; SLPI; -.
DR GenomeRNAi; 6590; -.
DR Pharos; P03973; Tbio.
DR PRO; PR:P03973; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; P03973; protein.
DR Bgee; ENSG00000124107; Expressed in trachea and 189 other tissues.
DR Genevisible; P03973; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA.
DR GO; GO:0035580; C:specific granule lumen; TAS:Reactome.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; IPI:UniProtKB.
DR GO; GO:0003729; F:mRNA binding; IDA:UniProtKB.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IDA:UniProtKB.
DR GO; GO:0019731; P:antibacterial humoral response; IDA:UniProtKB.
DR GO; GO:0006955; P:immune response; ISS:UniProtKB.
DR GO; GO:0045087; P:innate immune response; ISS:UniProtKB.
DR GO; GO:0035821; P:modulation of process of another organism; IDA:UniProtKB.
DR GO; GO:0032091; P:negative regulation of protein binding; IDA:UniProtKB.
DR GO; GO:0045071; P:negative regulation of viral genome replication; IDA:UniProtKB.
DR GO; GO:0032496; P:response to lipopolysaccharide; ISS:UniProtKB.
DR Gene3D; 4.10.75.10; -; 2.
DR InterPro; IPR036645; Elafin-like_sf.
DR InterPro; IPR008197; WAP_dom.
DR Pfam; PF00095; WAP; 2.
DR PRINTS; PR00003; 4DISULPHCORE.
DR SMART; SM00217; WAP; 2.
DR SUPFAM; SSF57256; SSF57256; 2.
DR PROSITE; PS51390; WAP; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic; Antimicrobial; Direct protein sequencing;
KW Disulfide bond; Immunity; Innate immunity; Protease inhibitor;
KW Reference proteome; Repeat; Secreted; Serine protease inhibitor; Signal.
FT SIGNAL 1..25
FT /evidence="ECO:0000269|PubMed:2039600,
FT ECO:0000269|PubMed:25946035, ECO:0000269|PubMed:3462719,
FT ECO:0000269|PubMed:3485543"
FT CHAIN 26..132
FT /note="Antileukoproteinase"
FT /id="PRO_0000041355"
FT DOMAIN 28..76
FT /note="WAP 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00722"
FT DOMAIN 82..130
FT /note="WAP 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00722"
FT REGION 84..132
FT /note="Elastase inhibitory domain"
FT SITE 97..98
FT /note="Reactive bond for chymotrypsin, trypsin and
FT elastase"
FT /evidence="ECO:0000305|PubMed:18421166,
FT ECO:0000305|PubMed:24121345, ECO:0000305|PubMed:3366116"
FT DISULFID 35..64
FT /evidence="ECO:0000269|PubMed:3366116"
FT DISULFID 43..68
FT /evidence="ECO:0000269|PubMed:3366116"
FT DISULFID 51..63
FT /evidence="ECO:0000269|PubMed:3366116"
FT DISULFID 57..72
FT /evidence="ECO:0000269|PubMed:3366116"
FT DISULFID 89..118
FT /evidence="ECO:0000269|PubMed:3366116,
FT ECO:0007744|PDB:2Z7F, ECO:0007744|PDB:4DOQ"
FT DISULFID 96..122
FT /evidence="ECO:0000269|PubMed:3366116,
FT ECO:0007744|PDB:2Z7F, ECO:0007744|PDB:4DOQ"
FT DISULFID 105..117
FT /evidence="ECO:0000269|PubMed:3366116,
FT ECO:0007744|PDB:2Z7F, ECO:0007744|PDB:4DOQ"
FT DISULFID 111..126
FT /evidence="ECO:0000269|PubMed:3366116,
FT ECO:0007744|PDB:2Z7F, ECO:0007744|PDB:4DOQ"
FT MUTAGEN 45
FT /note="R->G: No significant effect on inhibition of
FT elastase, trypsin and chymotrypsin."
FT /evidence="ECO:0000269|PubMed:10702419,
FT ECO:0000269|PubMed:2110563"
FT MUTAGEN 45
FT /note="R->M,V: No significant effect on inhibition of
FT elastase, trypsin and chymotrypsin."
FT /evidence="ECO:0000269|PubMed:2110563"
FT MUTAGEN 97
FT /note="L->F: Increases inhibition of chymotrypsin."
FT /evidence="ECO:0000269|PubMed:10702419,
FT ECO:0000269|PubMed:2110563"
FT MUTAGEN 97
FT /note="L->G: Reduced inhibition of elastase. Strongly
FT reduced inhibition of chymotrypsin and trypsin."
FT /evidence="ECO:0000269|PubMed:10702419,
FT ECO:0000269|PubMed:2110563"
FT MUTAGEN 97
FT /note="L->K,R: Strongly reduced inhibition of elastase.
FT Abolishes inhibition of trypsin."
FT /evidence="ECO:0000269|PubMed:10702419,
FT ECO:0000269|PubMed:2110563"
FT MUTAGEN 98
FT /note="M->G: No significant effect on inhibition of
FT elastase, trypsin and chymotrypsin."
FT /evidence="ECO:0000269|PubMed:2110563"
FT MUTAGEN 99
FT /note="L->G: No significant effect on inhibition of
FT elastase, trypsin and chymotrypsin."
FT /evidence="ECO:0000269|PubMed:2110563"
FT STRAND 86..88
FT /evidence="ECO:0007829|PDB:2Z7F"
FT STRAND 95..97
FT /evidence="ECO:0007829|PDB:2Z7F"
FT HELIX 108..110
FT /evidence="ECO:0007829|PDB:2Z7F"
FT STRAND 116..120
FT /evidence="ECO:0007829|PDB:2Z7F"
FT STRAND 123..127
FT /evidence="ECO:0007829|PDB:2Z7F"
SQ SEQUENCE 132 AA; 14326 MW; B62F3221E0903D90 CRC64;
MKSSGLFPFL VLLALGTLAP WAVEGSGKSF KAGVCPPKKS AQCLRYKKPE CQSDWQCPGK
KRCCPDTCGI KCLDPVDTPN PTRRKPGKCP VTYGQCLMLN PPNFCEMDGQ CKRDLKCCMG
MCGKSCVSPV KA
