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Elafin (Elastase-specific inhibitor) (ESI) (Peptidase inhibitor 3) (PI-3) (Protease inhibitor WAP3) (Skin-derived antileukoproteinase) (SKALP) (WAP four-disulfide core domain protein 14)

 ELAF_HUMAN              Reviewed;         117 AA.
P19957; E1P618; Q6FG74;
01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
01-DEC-1992, sequence version 3.
12-SEP-2018, entry version 183.
RecName: Full=Elafin;
AltName: Full=Elastase-specific inhibitor;
Short=ESI;
AltName: Full=Peptidase inhibitor 3;
Short=PI-3;
AltName: Full=Protease inhibitor WAP3;
AltName: Full=Skin-derived antileukoproteinase;
Short=SKALP;
AltName: Full=WAP four-disulfide core domain protein 14;
Flags: Precursor;
Name=PI3; Synonyms=WAP3, WFDC14;
Homo sapiens (Human).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
NCBI_TaxID=9606;
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
PubMed=1339270; DOI=10.1016/S0006-291X(05)80981-7;
Saheki T., Ito F., Hagiwara H., Saito Y., Kuroki J., Tachibana S.,
Hirose S.;
"Primary structure of the human elafin precursor preproelafin deduced
from the nucleotide sequence of its gene and the presence of unique
repetitive sequences in the prosegment.";
Biochem. Biophys. Res. Commun. 185:240-245(1992).
[2]
NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 23-48 AND 85-100.
TISSUE=Keratinocyte;
PubMed=7685029;
Molhuizen H.O.F., Alkemade H.A.C., Zeeuwen P.L.J.M., de Jongh G.J.,
Wieringa B., Schalkwijk J.;
"SKALP/elafin: an elastase inhibitor from cultured human
keratinocytes. Purification, cDNA sequence, and evidence for
transglutaminase cross-linking.";
J. Biol. Chem. 268:12028-12032(1993).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
TISSUE=Placenta;
PubMed=8476637; DOI=10.1165/ajrcmb/8.4.439;
Sallenave J.-M., Silva A.;
"Characterization and gene sequence of the precursor of elafin, an
elastase-specific inhibitor in bronchial secretions.";
Am. J. Respir. Cell Mol. Biol. 8:439-445(1993).
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
"Cloning of human full open reading frames in Gateway(TM) system entry
vector (pDONR201).";
Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
PubMed=11780052; DOI=10.1038/414865a;
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.;
"The DNA sequence and comparative analysis of human chromosome 20.";
Nature 414:865-871(2001).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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.
[7]
NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
TISSUE=Brain;
PubMed=15489334; DOI=10.1101/gr.2596504;
The MGC Project Team;
"The status, quality, and expansion of the NIH full-length cDNA
project: the Mammalian Gene Collection (MGC).";
Genome Res. 14:2121-2127(2004).
[8]
PROTEIN SEQUENCE OF 61-117.
TISSUE=Stratum corneum;
PubMed=2394696;
Wiedow O., Schroeder J.-M., Gregory H., Young J.A., Christophers E.;
"Elafin: an elastase-specific inhibitor of human skin. Purification,
characterization, and complete amino acid sequence.";
J. Biol. Chem. 265:14791-14795(1990).
[9]
ERRATUM.
Wiedow O., Schroeder J.-M., Gregory H., Young J.A., Christophers E.;
J. Biol. Chem. 266:3356-3356(1991).
[10]
PROTEIN SEQUENCE OF 70-94.
TISSUE=Sputum;
PubMed=2039600; DOI=10.1515/bchm3.1991.372.1.13;
Sallenave J.-M., Ryle A.P.;
"Purification and characterization of elastase-specific inhibitor.
Sequence homology with mucus proteinase inhibitor.";
Biol. Chem. Hoppe-Seyler 372:13-21(1991).
[11]
PROTEIN SEQUENCE OF 61-77.
TISSUE=Sputum;
PubMed=1536690; DOI=10.1515/bchm3.1992.373.1.27;
Sallenave J.-M., Marsden M.D., Ryle A.P.;
"Isolation of elafin and elastase-specific inhibitor (ESI) from
bronchial secretions. Evidence of sequence homology and immunological
cross-reactivity.";
Biol. Chem. Hoppe-Seyler 373:27-33(1992).
[12]
PROTEIN SEQUENCE OF 85-100.
TISSUE=Keratinocyte;
PubMed=2001428; DOI=10.1016/0925-4439(91)90053-C;
Schalkwijk J., de Roo C., de Jongh G.J.;
"Skin-derived antileukoproteinase (SKALP), an elastase inhibitor from
human keratinocytes. Purification and biochemical properties.";
Biochim. Biophys. Acta 1096:148-154(1991).
[13]
X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
PubMed=8794736; DOI=10.1021/bi960900l;
Tsunemi M., Matsuura Y., Sakakibara S., Katsube Y.;
"Crystal structure of an elastase-specific inhibitor elafin complexed
with porcine pancreatic elastase determined at 1.9-A resolution.";
Biochemistry 35:11570-11576(1996).
[14]
STRUCTURE BY NMR.
PubMed=9171290; DOI=10.1006/jmbi.1997.0983;
Francart C., Dauchez M., Alix A.J.P., Lippens G.;
"Solution structure of R-elafin, a specific inhibitor of elastase.";
J. Mol. Biol. 268:666-677(1997).
-!- FUNCTION: Neutrophil and pancreatic elastase-specific inhibitor of
skin. It may prevent elastase-mediated tissue proteolysis.
-!- SUBCELLULAR LOCATION: Secreted.
-!- DOMAIN: Consists of two domains: the transglutaminase substrate
domain (cementoin moiety) and the elastase inhibitor domain. The
transglutaminase substrate domain serves as an anchor to localize
elafin covalently to specific sites on extracellular matrix
proteins.
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EMBL; Z18538; CAA79223.1; -; mRNA.
EMBL; D13156; BAA02441.1; -; Genomic_DNA.
EMBL; S58717; AAB26371.1; -; Genomic_DNA.
EMBL; L10343; AAA36483.1; -; Genomic_DNA.
EMBL; CR542234; CAG47030.1; -; mRNA.
EMBL; AL049767; -; NOT_ANNOTATED_CDS; Genomic_DNA.
EMBL; CH471077; EAW75873.1; -; Genomic_DNA.
EMBL; CH471077; EAW75874.1; -; Genomic_DNA.
EMBL; BC010952; AAH10952.1; -; mRNA.
CCDS; CCDS13344.1; -.
PIR; JH0614; JH0614.
RefSeq; NP_002629.1; NM_002638.3.
UniGene; Hs.112341; -.
PDB; 1FLE; X-ray; 1.90 A; I=61-117.
PDB; 2REL; NMR; -; A=61-117.
PDB; 6ATU; X-ray; 2.40 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R=61-117.
PDBsum; 1FLE; -.
PDBsum; 2REL; -.
PDBsum; 6ATU; -.
ProteinModelPortal; P19957; -.
SMR; P19957; -.
BioGrid; 111284; 3.
MINT; P19957; -.
STRING; 9606.ENSP00000243924; -.
MEROPS; I17.002; -.
iPTMnet; P19957; -.
PhosphoSitePlus; P19957; -.
BioMuta; PI3; -.
DMDM; 119262; -.
EPD; P19957; -.
MaxQB; P19957; -.
PaxDb; P19957; -.
PeptideAtlas; P19957; -.
PRIDE; P19957; -.
ProteomicsDB; 53703; -.
DNASU; 5266; -.
Ensembl; ENST00000243924; ENSP00000243924; ENSG00000124102.
GeneID; 5266; -.
KEGG; hsa:5266; -.
UCSC; uc002xng.4; human.
CTD; 5266; -.
DisGeNET; 5266; -.
EuPathDB; HostDB:ENSG00000124102.4; -.
GeneCards; PI3; -.
HGNC; HGNC:8947; PI3.
HPA; CAB009449; -.
HPA; HPA017737; -.
MIM; 182257; gene.
neXtProt; NX_P19957; -.
OpenTargets; ENSG00000124102; -.
PharmGKB; PA33283; -.
eggNOG; ENOG410JDCZ; Eukaryota.
eggNOG; ENOG410XX92; LUCA.
GeneTree; ENSGT00530000064218; -.
HOGENOM; HOG000115819; -.
HOVERGEN; HBG018073; -.
InParanoid; P19957; -.
OMA; LIRCAMM; -.
OrthoDB; EOG091G12MK; -.
PhylomeDB; P19957; -.
TreeFam; TF340462; -.
Reactome; R-HSA-6803157; Antimicrobial peptides.
Reactome; R-HSA-6809371; Formation of the cornified envelope.
ChiTaRS; PI3; human.
EvolutionaryTrace; P19957; -.
GeneWiki; Elafin; -.
GenomeRNAi; 5266; -.
PMAP-CutDB; P19957; -.
PRO; PR:P19957; -.
Proteomes; UP000005640; Chromosome 20.
Bgee; ENSG00000124102; Expressed in 130 organ(s), highest expression level in lower esophagus mucosa.
CleanEx; HS_PI3; -.
Genevisible; P19957; HS.
GO; GO:0001533; C:cornified envelope; IDA:CAFA.
GO; GO:0005829; C:cytosol; TAS:Reactome.
GO; GO:0031012; C:extracellular matrix; TAS:ProtInc.
GO; GO:0005576; C:extracellular region; TAS:Reactome.
GO; GO:0004866; F:endopeptidase inhibitor activity; TAS:ProtInc.
GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; TAS:ProtInc.
GO; GO:0030280; F:structural constituent of epidermis; IDA:CAFA.
GO; GO:0019730; P:antimicrobial humoral response; TAS:Reactome.
GO; GO:0007620; P:copulation; IEA:InterPro.
GO; GO:0070268; P:cornification; TAS:Reactome.
GO; GO:0018149; P:peptide cross-linking; IDA:CAFA.
Gene3D; 4.10.75.10; -; 1.
InterPro; IPR036645; Elafin-like_sf.
InterPro; IPR002098; SVP_I.
InterPro; IPR019541; Trappin_transglut-bd_rpt.
InterPro; IPR008197; WAP_dom.
Pfam; PF10511; Cementoin; 2.
Pfam; PF00095; WAP; 1.
PRINTS; PR00003; 4DISULPHCORE.
SMART; SM00217; WAP; 1.
SUPFAM; SSF57256; SSF57256; 1.
PROSITE; PS00313; SVP_I; 2.
PROSITE; PS51390; WAP; 1.
1: Evidence at protein level;
3D-structure; Complete proteome; Direct protein sequencing;
Disulfide bond; Polymorphism; Protease inhibitor; Reference proteome;
Repeat; Secreted; Serine protease inhibitor; Signal.
SIGNAL 1 22 {ECO:0000269|PubMed:7685029}.
PROPEP 23 60 {ECO:0000269|PubMed:1536690,
ECO:0000269|PubMed:2394696}.
/FTId=PRO_0000041357.
CHAIN 61 117 Elafin.
/FTId=PRO_0000041358.
REPEAT 29 54 SVP-1 clotting 1.
REPEAT 55 72 SVP-1 clotting 2.
DOMAIN 69 117 WAP. {ECO:0000255|PROSITE-
ProRule:PRU00722}.
REGION 29 72 2 X tandem repeats of SVP-1 like motif.
DISULFID 76 105
DISULFID 83 109
DISULFID 92 104
DISULFID 98 113
VARIANT 17 17 T -> M (in dbSNP:rs17333103).
/FTId=VAR_052947.
VARIANT 34 34 T -> P (in dbSNP:rs2664581).
/FTId=VAR_024695.
CONFLICT 91 92 RC -> CP (in Ref. 10; AA sequence).
{ECO:0000305}.
STRAND 65 69 {ECO:0000244|PDB:2REL}.
STRAND 73 75 {ECO:0000244|PDB:1FLE}.
STRAND 81 84 {ECO:0000244|PDB:1FLE}.
HELIX 95 97 {ECO:0000244|PDB:1FLE}.
STRAND 98 101 {ECO:0000244|PDB:1FLE}.
STRAND 103 106 {ECO:0000244|PDB:1FLE}.
STRAND 108 114 {ECO:0000244|PDB:1FLE}.
SEQUENCE 117 AA; 12270 MW; A51D46257E5B03EF CRC64;
MRASSFLIVV VFLIAGTLVL EAAVTGVPVK GQDTVKGRVP FNGQDPVKGQ VSVKGQDKVK
AQEPVKGPVS TKPGSCPIIL IRCAMLNPPN RCLKDTDCPG IKKCCEGSCG MACFVPQ


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