ELAF_HUMAN
ID ELAF_HUMAN Reviewed; 117 AA.
AC P19957; E1P618; Q6FG74;
DT 01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-1992, sequence version 3.
DT 03-AUG-2022, entry version 202.
DE RecName: Full=Elafin;
DE AltName: Full=Elastase-specific inhibitor;
DE Short=ESI;
DE AltName: Full=Peptidase inhibitor 3;
DE Short=PI-3;
DE AltName: Full=Protease inhibitor WAP3;
DE AltName: Full=Skin-derived antileukoproteinase;
DE Short=SKALP;
DE AltName: Full=WAP four-disulfide core domain protein 14;
DE Flags: Precursor;
GN Name=PI3; Synonyms=WAP3, WFDC14;
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 [GENOMIC DNA].
RX PubMed=1339270; DOI=10.1016/s0006-291x(05)80981-7;
RA Saheki T., Ito F., Hagiwara H., Saito Y., Kuroki J., Tachibana S.,
RA Hirose S.;
RT "Primary structure of the human elafin precursor preproelafin deduced from
RT the nucleotide sequence of its gene and the presence of unique repetitive
RT sequences in the prosegment.";
RL Biochem. Biophys. Res. Commun. 185:240-245(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND PROTEIN SEQUENCE OF 23-48 AND 85-100.
RC TISSUE=Keratinocyte;
RX PubMed=7685029; DOI=10.1016/s0021-9258(19)50303-9;
RA Molhuizen H.O.F., Alkemade H.A.C., Zeeuwen P.L.J.M., de Jongh G.J.,
RA Wieringa B., Schalkwijk J.;
RT "SKALP/elafin: an elastase inhibitor from cultured human keratinocytes.
RT Purification, cDNA sequence, and evidence for transglutaminase cross-
RT linking.";
RL J. Biol. Chem. 268:12028-12032(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Placenta;
RX PubMed=8476637; DOI=10.1165/ajrcmb/8.4.439;
RA Sallenave J.-M., Silva A.;
RT "Characterization and gene sequence of the precursor of elafin, an
RT elastase-specific inhibitor in bronchial secretions.";
RL Am. J. Respir. Cell Mol. Biol. 8:439-445(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
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=Brain;
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 61-117.
RC TISSUE=Stratum corneum;
RX PubMed=2394696; DOI=10.1016/s0021-9258(18)77182-2;
RA Wiedow O., Schroeder J.-M., Gregory H., Young J.A., Christophers E.;
RT "Elafin: an elastase-specific inhibitor of human skin. Purification,
RT characterization, and complete amino acid sequence.";
RL J. Biol. Chem. 265:14791-14795(1990).
RN [9]
RP ERRATUM OF PUBMED:2394696.
RA Wiedow O., Schroeder J.-M., Gregory H., Young J.A., Christophers E.;
RL J. Biol. Chem. 266:3356-3356(1991).
RN [10]
RP PROTEIN SEQUENCE OF 70-94.
RC TISSUE=Sputum;
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 61-77.
RC TISSUE=Sputum;
RX PubMed=1536690; DOI=10.1515/bchm3.1992.373.1.27;
RA Sallenave J.-M., Marsden M.D., Ryle A.P.;
RT "Isolation of elafin and elastase-specific inhibitor (ESI) from bronchial
RT secretions. Evidence of sequence homology and immunological cross-
RT reactivity.";
RL Biol. Chem. Hoppe-Seyler 373:27-33(1992).
RN [12]
RP PROTEIN SEQUENCE OF 85-100.
RC TISSUE=Keratinocyte;
RX PubMed=2001428; DOI=10.1016/0925-4439(91)90053-c;
RA Schalkwijk J., de Roo C., de Jongh G.J.;
RT "Skin-derived antileukoproteinase (SKALP), an elastase inhibitor from human
RT keratinocytes. Purification and biochemical properties.";
RL Biochim. Biophys. Acta 1096:148-154(1991).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS), AND DISULFIDE BOND.
RX PubMed=8794736; DOI=10.1021/bi960900l;
RA Tsunemi M., Matsuura Y., Sakakibara S., Katsube Y.;
RT "Crystal structure of an elastase-specific inhibitor elafin complexed with
RT porcine pancreatic elastase determined at 1.9-A resolution.";
RL Biochemistry 35:11570-11576(1996).
RN [14]
RP STRUCTURE BY NMR, AND DISULFIDE BOND.
RX PubMed=9171290; DOI=10.1006/jmbi.1997.0983;
RA Francart C., Dauchez M., Alix A.J.P., Lippens G.;
RT "Solution structure of R-elafin, a specific inhibitor of elastase.";
RL J. Mol. Biol. 268:666-677(1997).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) OF 61-117, SYNTHESIS OF 61-117,
RP DISULFIDE BONDS, AND FUNCTION.
RX PubMed=29483648; DOI=10.1038/s41594-018-0033-9;
RA Correnti C.E., Gewe M.M., Mehlin C., Bandaranayake A.D., Johnsen W.A.,
RA Rupert P.B., Brusniak M.Y., Clarke M., Burke S.E., De Van Der Schueren W.,
RA Pilat K., Turnbaugh S.M., May D., Watson A., Chan M.K., Bahl C.D.,
RA Olson J.M., Strong R.K.;
RT "Screening, large-scale production and structure-based classification of
RT cystine-dense peptides.";
RL Nat. Struct. Mol. Biol. 25:270-278(2018).
CC -!- FUNCTION: Neutrophil and pancreatic elastase-specific inhibitor of
CC skin. It may prevent elastase-mediated tissue proteolysis. Has been
CC shown to inhibit the alpha-4-beta-2/CHRNA2-CHRNB2 nicotinic
CC acetylcholine receptor and to produce a weak inhibition on
CC Kv11.1/KCNH2/ERG1 and on the transient receptor potential cation
CC channel subfamily V member 1 (TRPV1) (PubMed:29483648).
CC {ECO:0000269|PubMed:29483648}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- DOMAIN: Consists of two domains: the transglutaminase substrate domain
CC (cementoin moiety) and the elastase inhibitor domain. The
CC transglutaminase substrate domain serves as an anchor to localize
CC elafin covalently to specific sites on extracellular matrix proteins.
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DR EMBL; Z18538; CAA79223.1; -; mRNA.
DR EMBL; D13156; BAA02441.1; -; Genomic_DNA.
DR EMBL; S58717; AAB26371.1; -; Genomic_DNA.
DR EMBL; L10343; AAA36483.1; -; Genomic_DNA.
DR EMBL; CR542234; CAG47030.1; -; mRNA.
DR EMBL; AL049767; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW75873.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW75874.1; -; Genomic_DNA.
DR EMBL; BC010952; AAH10952.1; -; mRNA.
DR CCDS; CCDS13344.1; -.
DR PIR; JH0614; JH0614.
DR RefSeq; NP_002629.1; NM_002638.3.
DR PDB; 1FLE; X-ray; 1.90 A; I=61-117.
DR PDB; 2REL; NMR; -; A=61-117.
DR 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.
DR PDBsum; 1FLE; -.
DR PDBsum; 2REL; -.
DR PDBsum; 6ATU; -.
DR AlphaFoldDB; P19957; -.
DR BMRB; P19957; -.
DR SMR; P19957; -.
DR BioGRID; 111284; 9.
DR MINT; P19957; -.
DR STRING; 9606.ENSP00000243924; -.
DR MEROPS; I17.002; -.
DR iPTMnet; P19957; -.
DR PhosphoSitePlus; P19957; -.
DR BioMuta; PI3; -.
DR DMDM; 119262; -.
DR EPD; P19957; -.
DR jPOST; P19957; -.
DR MassIVE; P19957; -.
DR MaxQB; P19957; -.
DR PaxDb; P19957; -.
DR PeptideAtlas; P19957; -.
DR PRIDE; P19957; -.
DR ProteomicsDB; 53703; -.
DR Antibodypedia; 1726; 285 antibodies from 32 providers.
DR DNASU; 5266; -.
DR Ensembl; ENST00000243924.4; ENSP00000243924.3; ENSG00000124102.5.
DR GeneID; 5266; -.
DR KEGG; hsa:5266; -.
DR MANE-Select; ENST00000243924.4; ENSP00000243924.3; NM_002638.4; NP_002629.1.
DR UCSC; uc002xng.4; human.
DR CTD; 5266; -.
DR DisGeNET; 5266; -.
DR GeneCards; PI3; -.
DR HGNC; HGNC:8947; PI3.
DR HPA; ENSG00000124102; Group enriched (esophagus, lymphoid tissue, vagina).
DR MIM; 182257; gene.
DR neXtProt; NX_P19957; -.
DR OpenTargets; ENSG00000124102; -.
DR PharmGKB; PA33283; -.
DR VEuPathDB; HostDB:ENSG00000124102; -.
DR eggNOG; ENOG502SZ79; Eukaryota.
DR GeneTree; ENSGT00530000064218; -.
DR HOGENOM; CLU_149429_0_0_1; -.
DR InParanoid; P19957; -.
DR OMA; QCAMLNP; -.
DR OrthoDB; 1560605at2759; -.
DR PhylomeDB; P19957; -.
DR TreeFam; TF340462; -.
DR PathwayCommons; P19957; -.
DR Reactome; R-HSA-6803157; Antimicrobial peptides.
DR Reactome; R-HSA-6809371; Formation of the cornified envelope.
DR SignaLink; P19957; -.
DR BioGRID-ORCS; 5266; 13 hits in 1057 CRISPR screens.
DR ChiTaRS; PI3; human.
DR EvolutionaryTrace; P19957; -.
DR GeneWiki; Elafin; -.
DR GenomeRNAi; 5266; -.
DR Pharos; P19957; Tbio.
DR PRO; PR:P19957; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; P19957; protein.
DR Bgee; ENSG00000124102; Expressed in lower esophagus mucosa and 122 other tissues.
DR Genevisible; P19957; HS.
DR GO; GO:0001533; C:cornified envelope; IDA:CAFA.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0031012; C:extracellular matrix; TAS:ProtInc.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0004866; F:endopeptidase inhibitor activity; TAS:ProtInc.
DR GO; GO:0004867; F:serine-type endopeptidase inhibitor activity; IBA:GO_Central.
DR GO; GO:0030280; F:structural constituent of skin epidermis; IDA:CAFA.
DR GO; GO:0019731; P:antibacterial humoral response; IBA:GO_Central.
DR GO; GO:0007620; P:copulation; IEA:InterPro.
DR GO; GO:0045087; P:innate immune response; IBA:GO_Central.
DR GO; GO:0018149; P:peptide cross-linking; IDA:CAFA.
DR Gene3D; 4.10.75.10; -; 1.
DR InterPro; IPR036645; Elafin-like_sf.
DR InterPro; IPR002098; SVP_I.
DR InterPro; IPR019541; Trappin_transglut-bd_rpt.
DR InterPro; IPR008197; WAP_dom.
DR Pfam; PF10511; Cementoin; 2.
DR Pfam; PF00095; WAP; 1.
DR PRINTS; PR00003; 4DISULPHCORE.
DR SMART; SM00217; WAP; 1.
DR SUPFAM; SSF57256; SSF57256; 1.
DR PROSITE; PS00313; SVP_I; 2.
DR PROSITE; PS51390; WAP; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Disulfide bond;
KW Protease inhibitor; Reference proteome; Repeat; Secreted;
KW Serine protease inhibitor; Signal.
FT SIGNAL 1..22
FT /evidence="ECO:0000269|PubMed:7685029"
FT PROPEP 23..60
FT /evidence="ECO:0000269|PubMed:1536690,
FT ECO:0000269|PubMed:2394696"
FT /id="PRO_0000041357"
FT CHAIN 61..117
FT /note="Elafin"
FT /id="PRO_0000041358"
FT REPEAT 29..54
FT /note="SVP-1 clotting 1"
FT REPEAT 55..72
FT /note="SVP-1 clotting 2"
FT DOMAIN 69..117
FT /note="WAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00722"
FT REGION 29..72
FT /note="2 X tandem repeats of SVP-1 like motif"
FT DISULFID 76..105
FT /evidence="ECO:0000269|PubMed:29483648,
FT ECO:0000269|PubMed:8794736, ECO:0000269|PubMed:9171290,
FT ECO:0000312|PDB:1FLE, ECO:0000312|PDB:2REL,
FT ECO:0000312|PDB:6ATU"
FT DISULFID 83..109
FT /evidence="ECO:0000269|PubMed:29483648,
FT ECO:0000269|PubMed:8794736, ECO:0000269|PubMed:9171290,
FT ECO:0000312|PDB:1FLE, ECO:0000312|PDB:2REL,
FT ECO:0000312|PDB:6ATU"
FT DISULFID 92..104
FT /evidence="ECO:0000269|PubMed:29483648,
FT ECO:0000269|PubMed:8794736, ECO:0000269|PubMed:9171290,
FT ECO:0000312|PDB:1FLE, ECO:0000312|PDB:2REL,
FT ECO:0000312|PDB:6ATU"
FT DISULFID 98..113
FT /evidence="ECO:0000269|PubMed:29483648,
FT ECO:0000269|PubMed:8794736, ECO:0000269|PubMed:9171290,
FT ECO:0000312|PDB:1FLE, ECO:0000312|PDB:2REL,
FT ECO:0000312|PDB:6ATU"
FT VARIANT 17
FT /note="T -> M (in dbSNP:rs17333103)"
FT /id="VAR_052947"
FT VARIANT 34
FT /note="T -> P (in dbSNP:rs2664581)"
FT /id="VAR_024695"
FT CONFLICT 91..92
FT /note="RC -> CP (in Ref. 10; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 65..69
FT /evidence="ECO:0007829|PDB:2REL"
FT STRAND 73..75
FT /evidence="ECO:0007829|PDB:1FLE"
FT STRAND 81..84
FT /evidence="ECO:0007829|PDB:1FLE"
FT HELIX 95..97
FT /evidence="ECO:0007829|PDB:1FLE"
FT STRAND 98..101
FT /evidence="ECO:0007829|PDB:1FLE"
FT STRAND 103..106
FT /evidence="ECO:0007829|PDB:1FLE"
FT STRAND 108..114
FT /evidence="ECO:0007829|PDB:1FLE"
SQ SEQUENCE 117 AA; 12270 MW; A51D46257E5B03EF CRC64;
MRASSFLIVV VFLIAGTLVL EAAVTGVPVK GQDTVKGRVP FNGQDPVKGQ VSVKGQDKVK
AQEPVKGPVS TKPGSCPIIL IRCAMLNPPN RCLKDTDCPG IKKCCEGSCG MACFVPQ
