DEF5_HUMAN
ID DEF5_HUMAN Reviewed; 94 AA.
AC Q01523; A0JDY6; Q3KNV2;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1993, sequence version 1.
DT 03-AUG-2022, entry version 167.
DE RecName: Full=Defensin alpha 5 {ECO:0000312|HGNC:HGNC:2764};
DE AltName: Full=Defensin-5 {ECO:0000303|PubMed:1429669};
DE AltName: Full=HD5(20-94) {ECO:0000303|PubMed:12021776};
DE Contains:
DE RecName: Full=HD5(23-94) {ECO:0000303|PubMed:12021776};
DE Contains:
DE RecName: Full=HD5(29-94) {ECO:0000303|PubMed:12021776};
DE Contains:
DE RecName: Full=HD5(56-94) {ECO:0000303|PubMed:12021776};
DE Contains:
DE RecName: Full=HD5(63-94) {ECO:0000303|PubMed:12021776};
DE Flags: Precursor;
GN Name=DEFA5; Synonyms=DEF5;
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], AND TISSUE SPECIFICITY.
RC TISSUE=Intestine;
RX PubMed=1429669; DOI=10.1016/s0021-9258(18)50079-x;
RA Jones D.E., Bevins C.L.;
RT "Paneth cells of the human small intestine express an antimicrobial peptide
RT gene.";
RL J. Biol. Chem. 267:23216-23225(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [3]
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 (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
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 [5]
RP PARTIAL PROTEIN SEQUENCE, FUNCTION, PEPTIDE CHARACTERIZATION, PROTEOLYTIC
RP CLEAVAGE, GLYCOSYLATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RX PubMed=12021776; DOI=10.1038/ni797;
RA Ghosh D., Porter E., Shen B., Lee S.K., Wilk D., Drazba J., Yadav S.P.,
RA Crabb J.W., Ganz T., Bevins C.L.;
RT "Paneth cell trypsin is the processing enzyme for human defensin-5.";
RL Nat. Immunol. 3:583-590(2002).
RN [6]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND INDUCTION BY INFECTION.
RX PubMed=9588893;
RA Quayle A.J., Porter E.M., Nussbaum A.A., Wang Y.M., Brabec C., Yip K.P.,
RA Mok S.C.;
RT "Gene expression, immunolocalization, and secretion of human defensin-5 in
RT human female reproductive tract.";
RL Am. J. Pathol. 152:1247-1258(1998).
RN [7]
RP FUNCTION.
RX PubMed=12660734; DOI=10.1038/nature01520;
RA Salzman N.H., Ghosh D., Huttner K.M., Paterson Y., Bevins C.L.;
RT "Protection against enteric salmonellosis in transgenic mice expressing a
RT human intestinal defensin.";
RL Nature 422:522-526(2003).
RN [8]
RP FUNCTION.
RX PubMed=15616305; DOI=10.1128/aac.49.1.269-275.2005;
RA Ericksen B., Wu Z., Lu W., Lehrer R.I.;
RT "Antibacterial activity and specificity of the six human alpha-defensins.";
RL Antimicrob. Agents Chemother. 49:269-275(2005).
RN [9]
RP FUNCTION, TISSUE SPECIFICITY, AND INDUCTION BY PYELONEPHRITIS.
RX PubMed=22359618; DOI=10.1371/journal.pone.0031712;
RA Spencer J.D., Hains D.S., Porter E., Bevins C.L., DiRosario J.,
RA Becknell B., Wang H., Schwaderer A.L.;
RT "Human alpha defensin 5 expression in the human kidney and urinary tract.";
RL PLoS ONE 7:e31712-e31712(2012).
RN [10]
RP FUNCTION.
RX PubMed=25354318; DOI=10.1038/mi.2014.100;
RA Schroeder B.O., Ehmann D., Precht J.C., Castillo P.A., Kuechler R.,
RA Berger J., Schaller M., Stange E.F., Wehkamp J.;
RT "Paneth cell alpha-defensin 6 (HD-6) is an antimicrobial peptide.";
RL Mucosal Immunol. 8:661-671(2015).
RN [11]
RP FUNCTION, AND PROTEOLYTIC CLEAVAGE.
RX PubMed=30808760; DOI=10.1073/pnas.1817376116;
RA Ehmann D., Wendler J., Koeninger L., Larsen I.S., Klag T., Berger J.,
RA Marette A., Schaller M., Stange E.F., Malek N.P., Jensen B.A.H.,
RA Wehkamp J.;
RT "Paneth cell alpha-defensins HD-5 and HD-6 display differential degradation
RT into active antimicrobial fragments.";
RL Proc. Natl. Acad. Sci. U.S.A. 116:3746-3751(2019).
RN [12] {ECO:0007744|PDB:1ZMP}
RP X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) OF 63-94, FUNCTION, SUBUNIT, AND
RP DISULFIDE BONDS.
RX PubMed=17088326; DOI=10.1110/ps.062336606;
RA Szyk A., Wu Z., Tucker K., Yang D., Lu W., Lubkowski J.;
RT "Crystal structures of human alpha-defensins HNP4, HD5, and HD6.";
RL Protein Sci. 15:2749-2760(2006).
RN [13] {ECO:0007744|PDB:3I5W}
RP X-RAY CRYSTALLOGRAPHY (1.63 ANGSTROMS) OF 63-94 OF MUTANT HIS-71, FUNCTION,
RP DISULFIDE BONDS, VARIANT HIS-71, AND MUTAGENESIS OF ARG-71; ARG-75; ARG-90
RP AND ARG-94.
RX PubMed=19589339; DOI=10.1016/j.febslet.2009.06.051;
RA de Leeuw E., Rajabi M., Zou G., Pazgier M., Lu W.;
RT "Selective arginines are important for the antibacterial activity and host
RT cell interaction of human alpha-defensin 5.";
RL FEBS Lett. 583:2507-2512(2009).
RN [14] {ECO:0007744|PDB:2LXZ}
RP STRUCTURE BY NMR OF 63-94, SUBUNIT, DISULFIDE BONDS, AND MUTAGENESIS OF
RP CYS-67; CYS-72; CYS-92 AND CYS-93.
RX PubMed=23163963; DOI=10.1021/bi301255u;
RA Wommack A.J., Robson S.A., Wanniarachchi Y.A., Wan A., Turner C.J.,
RA Wagner G., Nolan E.M.;
RT "NMR solution structure and condition-dependent oligomerization of the
RT antimicrobial peptide human defensin 5.";
RL Biochemistry 51:9624-9637(2012).
RN [15] {ECO:0007744|PDB:4E82, ECO:0007744|PDB:4E83, ECO:0007744|PDB:4E86}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 63-94, FUNCTION, SUBUNIT,
RP INTERACTION WITH B.ANTRACIS LEF/LETHAL FACTOR, DISULFIDE BONDS, AND
RP MUTAGENESIS OF ARG-71; SER-77; LEU-88; TYR-89 AND LEU-91.
RX PubMed=22573326; DOI=10.1074/jbc.m112.367995;
RA Rajabi M., Ericksen B., Wu X., de Leeuw E., Zhao L., Pazgier M., Lu W.;
RT "Functional determinants of human enteric alpha-defensin HD5: crucial role
RT for hydrophobicity at dimer interface.";
RL J. Biol. Chem. 287:21615-21627(2012).
RN [16] {ECO:0007744|PDB:2MIT}
RP STRUCTURE BY NMR OF 63-94, AND DISULFIDE BONDS.
RA Wommack A.J., Ziarek J.J., Wagner G., Nolan E.M.;
RT "Solution structure of oxidized dimeric form of human defensin 5.";
RL Submitted (DEC-2013) to the PDB data bank.
RN [17] {ECO:0007744|PDB:4RBW, ECO:0007744|PDB:4RBX}
RP X-RAY CRYSTALLOGRAPHY (1.10 ANGSTROMS) OF 63-94 OF MUTANT ARG-7 AND ARG-83,
RP FUNCTION, SUBUNIT, DISULFIDE BONDS, AND MUTAGENESIS OF THR-69; GLU-83;
RP SER-85 AND GLY-86.
RX PubMed=25782105; DOI=10.1021/jm501824a;
RA Wang C., Shen M., Gohain N., Tolbert W.D., Chen F., Zhang N., Yang K.,
RA Wang A., Su Y., Cheng T., Zhao J., Pazgier M., Wang J.;
RT "Design of a potent antibiotic peptide based on the active region of human
RT defensin 5.";
RL J. Med. Chem. 58:3083-3093(2015).
RN [18] {ECO:0007744|PDB:5CUI, ECO:0007744|PDB:5CUJ, ECO:0007744|PDB:5CUM}
RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 63-94 OF MUTANT ALA-89 AND
RP ALA-90, FUNCTION (MICROBIAL INFECTION), SUBUNIT, DISULFIDE BONDS, AND
RP MUTAGENESIS OF LEU-88; TYR-89; ARG-90 AND LEU-91.
RX PubMed=29858013; DOI=10.1016/j.immuni.2018.04.014;
RA Xu D., Liao C., Zhang B., Tolbert W.D., He W., Dai Z., Zhang W., Yuan W.,
RA Pazgier M., Liu J., Yu J., Sansonetti P.J., Bevins C.L., Shao Y., Lu W.;
RT "Human Enteric alpha-Defensin 5 Promotes Shigella Infection by Enhancing
RT Bacterial Adhesion and Invasion.";
RL Immunity 48:1233-1244.e6(2018).
CC -!- FUNCTION: Host-defense peptide that maintains sterility in the
CC urogenital system (PubMed:12021776, PubMed:12660734, PubMed:15616305,
CC PubMed:22359618, PubMed:25354318, PubMed:30808760, PubMed:19589339,
CC PubMed:22573326, PubMed:25782105). Has antimicrobial activity against a
CC wide range of bacteria, including Gram-negative E.coli, P.aeruginosa
CC and S.typhimurium, and Gram-positive E.aerogenes, S.aureus, B. cereus,
CC E.faecium and L.monocytogenes (PubMed:12021776, PubMed:15616305,
CC PubMed:22359618, PubMed:25354318, PubMed:30808760, PubMed:19589339,
CC PubMed:22573326). Confers resistance to intestinal infection by
CC S.typhimurium (PubMed:12660734). Exhibits antimicrobial activity
CC against enteric commensal bacteria such as B.adolescentis,
CC L.acidophilus, B.breve, L.fermentum, B.longum and S.thermophilus
CC (PubMed:25354318). Binds to bacterial membranes and causes membrane
CC disintegration (PubMed:25782105). Induces the secretion of the
CC chemokine IL-8 by intestinal epithelial cells (PubMed:19589339). Binds
CC to B.antracis lef/lethal factor, a major virulence factor from
CC B.anthracis, and neutralizes its enzymatic activity (PubMed:22573326).
CC {ECO:0000269|PubMed:12021776, ECO:0000269|PubMed:12660734,
CC ECO:0000269|PubMed:15616305, ECO:0000269|PubMed:19589339,
CC ECO:0000269|PubMed:22359618, ECO:0000269|PubMed:22573326,
CC ECO:0000269|PubMed:25354318, ECO:0000269|PubMed:25782105,
CC ECO:0000269|PubMed:30808760}.
CC -!- FUNCTION: (Microbial infection) Acts as a target for S.flexneri
CC infection by binding to the bacterium, possibly via bacterial surface
CC proteins, and thereby augmenting infectivity via enhanced bacterial
CC adhesion and invasion of epithelial cells and tissues.
CC {ECO:0000269|PubMed:29858013}.
CC -!- SUBUNIT: Homodimer (PubMed:17088326, PubMed:22573326, PubMed:25782105,
CC PubMed:29858013). Homotetramer (PubMed:23163963). Interacts with
CC B.antracis lef/lethal factor (PubMed:22573326).
CC {ECO:0000269|PubMed:17088326, ECO:0000269|PubMed:22573326,
CC ECO:0000269|PubMed:23163963, ECO:0000269|PubMed:25782105,
CC ECO:0000269|PubMed:29858013}.
CC -!- INTERACTION:
CC Q01523; Q6FHY5: MEOX2; NbExp=3; IntAct=EBI-3908179, EBI-16439278;
CC PRO_0000417390; Q9BYF1: ACE2; NbExp=4; IntAct=EBI-25634589, EBI-7730807;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:12021776,
CC ECO:0000269|PubMed:9588893}. Cytoplasmic vesicle, secretory vesicle
CC {ECO:0000269|PubMed:12021776, ECO:0000269|PubMed:9588893}. Note=Stored
CC as propeptide HD5(20-94) in secretory granules of small intestinal
CC Paneth cells and found in the ileum lumen as processed mature peptides,
CC predominantly in the HD5(63-94) form (PubMed:12021776). Peptides
CC HD5(20-94), HD5(23-94) and HD5(29-94) are found within tissues, HD5(20-
CC 94) being the predominant intracellular form. Peptides HD5(56-94) and
CC HD5(63-94) are found in the extracellular milieu, HD5(63-94) being the
CC most abundant form (PubMed:12021776). Secreted into the female genital
CC tract lumen (PubMed:9588893). {ECO:0000269|PubMed:12021776,
CC ECO:0000269|PubMed:9588893}.
CC -!- TISSUE SPECIFICITY: Expressed in the gastrointestinal, reproductive,
CC and urinary tracts (at protein level) (PubMed:1429669, PubMed:12021776,
CC PubMed:9588893, PubMed:22359618). Expressed in Paneth cells of the
CC small intestine (at protein level) (PubMed:1429669, PubMed:12021776).
CC Expressed throughout the urothelium of the lower urinary tract and in
CC the collecting tubules of the kidney (at protein level)
CC (PubMed:22359618). Expressed in stratified squamous epithelial cells of
CC the female genital tract epithelia, such as in vagina, ectocervix,
CC endocervix, endometrium, and fallopian tube (at protein level)
CC (PubMed:9588893). Endometrial expression correlates with stages of the
CC menstrual cycle: Expression is low during the early proliferative
CC phase, increased during the mid- to late proliferative phase, peaks
CC during the early secretory phase of the cycle, and decreases during the
CC mid- to late secretory phase (PubMed:9588893).
CC {ECO:0000269|PubMed:12021776, ECO:0000269|PubMed:1429669,
CC ECO:0000269|PubMed:22359618, ECO:0000269|PubMed:9588893}.
CC -!- INDUCTION: Up-regulated in fallopian tubes upon infection
CC (PubMed:9588893). Increased expression in kidneys with pyelonephritis
CC (PubMed:22359618). {ECO:0000269|PubMed:22359618,
CC ECO:0000269|PubMed:9588893}.
CC -!- PTM: Glycosylated. {ECO:0000269|PubMed:12021776}.
CC -!- PTM: Proteolytically cleaved at Arg-62 by trypsin (PubMed:12021776).
CC Both the propeptide form proHD5/HD5(20-94) and HD5(56-94) are cleaved
CC into the lumenal peptide form HD5(63-94) by trypsin (PubMed:12021776).
CC Unprocessed proHD5 exerts antimicrobial activities, but peptide potency
CC is enhanced by peptide processing (PubMed:12021776). Proteolytically
CC cleaved in duodenal fluid; derived fragments are antimicrobially active
CC against commensal bacteria (in vitro) (PubMed:30808760).
CC {ECO:0000269|PubMed:12021776, ECO:0000269|PubMed:30808760}.
CC -!- PTM: (Microbial infection) The disulfide bridges and homodimerization
CC are a prerequisite for the enhancement of S.flexneri adhesion and
CC invasion. {ECO:0000269|PubMed:29858013}.
CC -!- SIMILARITY: Belongs to the alpha-defensin family. {ECO:0000305}.
CC -!- CAUTION: It was shown by two studies that dimerization of DEFA5 is
CC crucial for antimicrobial activity (PubMed:17088326, PubMed:22573326).
CC Another study, however, states that dimer formation is not
CC indispensable for antimicrobial activity of DEFA5 (PubMed:25782105).
CC {ECO:0000269|PubMed:17088326, ECO:0000269|PubMed:22573326,
CC ECO:0000269|PubMed:25782105}.
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DR EMBL; M97925; AAA35754.1; -; Genomic_DNA.
DR EMBL; AF238378; AAT68886.1; -; Genomic_DNA.
DR EMBL; CH471153; EAW80489.1; -; Genomic_DNA.
DR EMBL; BC069690; AAH69690.1; -; mRNA.
DR EMBL; BC107079; AAI07080.1; -; mRNA.
DR CCDS; CCDS5963.1; -.
DR PIR; A44454; A44454.
DR RefSeq; NP_066290.1; NM_021010.2.
DR PDB; 1ZMP; X-ray; 1.65 A; A/B/C/D=63-94.
DR PDB; 2LXZ; NMR; -; A=63-94.
DR PDB; 2MIT; NMR; -; A/B=63-94.
DR PDB; 3I5W; X-ray; 1.63 A; A/B=63-94.
DR PDB; 4E82; X-ray; 1.70 A; A/B=63-94.
DR PDB; 4E83; X-ray; 1.90 A; A/B=63-94.
DR PDB; 4E86; X-ray; 2.75 A; A/B/C/D/E/F/G/H/L=63-94.
DR PDB; 4RBW; X-ray; 1.50 A; A/B/C/D=63-94.
DR PDB; 4RBX; X-ray; 1.10 A; A=63-94.
DR PDB; 5CUI; X-ray; 2.40 A; A/B/C/D/E/F=63-94.
DR PDB; 5CUJ; X-ray; 2.08 A; A/B/C/D/E/F=63-94.
DR PDB; 5CUM; X-ray; 1.75 A; A/B/C=63-94.
DR PDBsum; 1ZMP; -.
DR PDBsum; 2LXZ; -.
DR PDBsum; 2MIT; -.
DR PDBsum; 3I5W; -.
DR PDBsum; 4E82; -.
DR PDBsum; 4E83; -.
DR PDBsum; 4E86; -.
DR PDBsum; 4RBW; -.
DR PDBsum; 4RBX; -.
DR PDBsum; 5CUI; -.
DR PDBsum; 5CUJ; -.
DR PDBsum; 5CUM; -.
DR AlphaFoldDB; Q01523; -.
DR BMRB; Q01523; -.
DR SMR; Q01523; -.
DR BioGRID; 108034; 119.
DR IntAct; Q01523; 65.
DR STRING; 9606.ENSP00000329890; -.
DR BioMuta; DEFA5; -.
DR DMDM; 399353; -.
DR jPOST; Q01523; -.
DR MassIVE; Q01523; -.
DR PaxDb; Q01523; -.
DR PeptideAtlas; Q01523; -.
DR PRIDE; Q01523; -.
DR ProteomicsDB; 57964; -.
DR Antibodypedia; 1967; 251 antibodies from 22 providers.
DR DNASU; 1670; -.
DR Ensembl; ENST00000330590.4; ENSP00000329890.2; ENSG00000164816.8.
DR Ensembl; ENST00000647159.2; ENSP00000494799.1; ENSG00000285251.2.
DR GeneID; 1670; -.
DR KEGG; hsa:1670; -.
DR MANE-Select; ENST00000330590.4; ENSP00000329890.2; NM_021010.3; NP_066290.1.
DR UCSC; uc003wra.2; human.
DR CTD; 1670; -.
DR DisGeNET; 1670; -.
DR GeneCards; DEFA5; -.
DR HGNC; HGNC:2764; DEFA5.
DR HPA; ENSG00000164816; Tissue enriched (intestine).
DR MIM; 600472; gene.
DR neXtProt; NX_Q01523; -.
DR OpenTargets; ENSG00000164816; -.
DR PharmGKB; PA27241; -.
DR VEuPathDB; HostDB:ENSG00000164816; -.
DR eggNOG; ENOG502T2EX; Eukaryota.
DR GeneTree; ENSGT00940000153268; -.
DR HOGENOM; CLU_160803_3_0_1; -.
DR InParanoid; Q01523; -.
DR OMA; ESHTGRC; -.
DR OrthoDB; 1610714at2759; -.
DR PhylomeDB; Q01523; -.
DR TreeFam; TF338414; -.
DR PathwayCommons; Q01523; -.
DR Reactome; R-HSA-1461973; Defensins.
DR Reactome; R-HSA-1462054; Alpha-defensins.
DR SignaLink; Q01523; -.
DR BioGRID-ORCS; 1670; 10 hits in 1060 CRISPR screens.
DR ChiTaRS; DEFA5; human.
DR EvolutionaryTrace; Q01523; -.
DR GeneWiki; DEFA5; -.
DR GenomeRNAi; 1670; -.
DR Pharos; Q01523; Tbio.
DR PRO; PR:Q01523; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q01523; protein.
DR Bgee; ENSG00000164816; Expressed in duodenum and 72 other tissues.
DR Genevisible; Q01523; HS.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA.
DR GO; GO:0030496; C:midbody; IDA:HPA.
DR GO; GO:0030141; C:secretory granule; IDA:UniProtKB.
DR GO; GO:0034774; C:secretory granule lumen; TAS:Reactome.
DR GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB.
DR GO; GO:0019731; P:antibacterial humoral response; IBA:GO_Central.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IBA:GO_Central.
DR GO; GO:0050832; P:defense response to fungus; IEA:UniProtKB-KW.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IDA:UniProtKB.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IMP:UniProtKB.
DR GO; GO:0002227; P:innate immune response in mucosa; IBA:GO_Central.
DR GO; GO:0051873; P:killing by host of symbiont cells; IDA:CACAO.
DR GO; GO:0031640; P:killing of cells of another organism; IDA:UniProtKB.
DR GO; GO:0051673; P:membrane disruption in another organism; IDA:UniProtKB.
DR GO; GO:0032757; P:positive regulation of interleukin-8 production; IDA:UniProtKB.
DR GO; GO:1905710; P:positive regulation of membrane permeability; IMP:UniProtKB.
DR GO; GO:0051289; P:protein homotetramerization; IDA:UniProtKB.
DR InterPro; IPR016327; Alpha-defensin.
DR InterPro; IPR006081; Alpha-defensin_C.
DR InterPro; IPR002366; Alpha-defensin_propep.
DR InterPro; IPR006080; Defensin_beta/alpha.
DR PANTHER; PTHR11876; PTHR11876; 1.
DR Pfam; PF00323; Defensin_1; 1.
DR Pfam; PF00879; Defensin_propep; 1.
DR PIRSF; PIRSF001875; Alpha-defensin; 1.
DR SMART; SM00048; DEFSN; 1.
DR PROSITE; PS00269; DEFENSIN; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic; Antimicrobial; Cytoplasmic vesicle; Defensin;
KW Direct protein sequencing; Disulfide bond; Fungicide; Glycoprotein;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PEPTIDE 20..94
FT /note="Defensin alpha 5"
FT /evidence="ECO:0000269|PubMed:12021776"
FT /id="PRO_0000006787"
FT PEPTIDE 23..94
FT /note="HD5(23-94)"
FT /evidence="ECO:0000269|PubMed:12021776"
FT /id="PRO_0000417387"
FT PEPTIDE 29..94
FT /note="HD5(29-94)"
FT /evidence="ECO:0000269|PubMed:12021776"
FT /id="PRO_0000417388"
FT PEPTIDE 56..94
FT /note="HD5(56-94)"
FT /evidence="ECO:0000269|PubMed:12021776"
FT /id="PRO_0000417389"
FT PEPTIDE 63..94
FT /note="HD5(63-94)"
FT /evidence="ECO:0000269|PubMed:12021776"
FT /id="PRO_0000417390"
FT DISULFID 65..93
FT /evidence="ECO:0000269|PubMed:17088326,
FT ECO:0000269|PubMed:19589339, ECO:0000269|PubMed:22573326,
FT ECO:0000269|PubMed:23163963, ECO:0000269|PubMed:25782105,
FT ECO:0000269|PubMed:29858013, ECO:0000269|Ref.16,
FT ECO:0007744|PDB:1ZMP, ECO:0007744|PDB:2LXZ,
FT ECO:0007744|PDB:2MIT, ECO:0007744|PDB:3I5W,
FT ECO:0007744|PDB:4E82, ECO:0007744|PDB:4E83,
FT ECO:0007744|PDB:4E86, ECO:0007744|PDB:4RBW,
FT ECO:0007744|PDB:4RBX, ECO:0007744|PDB:5CUI,
FT ECO:0007744|PDB:5CUJ, ECO:0007744|PDB:5CUM"
FT DISULFID 67..82
FT /evidence="ECO:0000269|PubMed:17088326,
FT ECO:0000269|PubMed:19589339, ECO:0000269|PubMed:22573326,
FT ECO:0000269|PubMed:23163963, ECO:0000269|PubMed:25782105,
FT ECO:0000269|PubMed:29858013, ECO:0000269|Ref.16,
FT ECO:0007744|PDB:1ZMP, ECO:0007744|PDB:2LXZ,
FT ECO:0007744|PDB:2MIT, ECO:0007744|PDB:3I5W,
FT ECO:0007744|PDB:4E82, ECO:0007744|PDB:4E83,
FT ECO:0007744|PDB:4E86, ECO:0007744|PDB:4RBW,
FT ECO:0007744|PDB:4RBX, ECO:0007744|PDB:5CUI,
FT ECO:0007744|PDB:5CUJ, ECO:0007744|PDB:5CUM"
FT DISULFID 72..92
FT /evidence="ECO:0000269|PubMed:17088326,
FT ECO:0000269|PubMed:19589339, ECO:0000269|PubMed:22573326,
FT ECO:0000269|PubMed:23163963, ECO:0000269|PubMed:25782105,
FT ECO:0000269|PubMed:29858013, ECO:0000269|Ref.16,
FT ECO:0007744|PDB:1ZMP, ECO:0007744|PDB:2LXZ,
FT ECO:0007744|PDB:2MIT, ECO:0007744|PDB:3I5W,
FT ECO:0007744|PDB:4E82, ECO:0007744|PDB:4E83,
FT ECO:0007744|PDB:4E86, ECO:0007744|PDB:4RBW,
FT ECO:0007744|PDB:4RBX, ECO:0007744|PDB:5CUI,
FT ECO:0007744|PDB:5CUJ, ECO:0007744|PDB:5CUM"
FT VARIANT 71
FT /note="R -> H (impairs antimicrobial activity against
FT S.aureus; dbSNP:rs7839771)"
FT /evidence="ECO:0000269|PubMed:19589339"
FT /id="VAR_059245"
FT MUTAGEN 67
FT /note="C->S: Prohibits tetramer formation; when associated
FT with S-93."
FT /evidence="ECO:0000269|PubMed:23163963"
FT MUTAGEN 69
FT /note="T->R: Enhanced antibacterial activity against both
FT E.coli and S.aureus. Enhanced membrane binding and membrane
FT disintegration abilities, as well as further increased
FT antibacterial activity; when associated with R-83."
FT /evidence="ECO:0000269|PubMed:25782105"
FT MUTAGEN 71
FT /note="R->A: Reduced killing of S.aureus and E.coli.
FT Impairs antimicrobial activity against E.coli, E.aerogenes,
FT S.aureus and B.cereus; when associated with A-90. Reduced
FT induction of IL-8 secretion; when associated with A-90."
FT /evidence="ECO:0000269|PubMed:19589339,
FT ECO:0000269|PubMed:22573326"
FT MUTAGEN 71
FT /note="R->K: Impairs antimicrobial activity against S.
FT aureus; when associated with K-90. Reduced induction of IL-
FT 8 secretion; when associated with K-90."
FT /evidence="ECO:0000269|PubMed:19589339"
FT MUTAGEN 72
FT /note="C->S: Prohibits tetramer formation; when associated
FT with S-92."
FT /evidence="ECO:0000269|PubMed:23163963"
FT MUTAGEN 75
FT /note="R->A: Impairs antimicrobial activity against E.coli,
FT E.aerogenes, S.aureus and B.cereus; when associated with A-
FT 94. Reduced induction of IL-8 secretion; when associated
FT with A-94."
FT /evidence="ECO:0000269|PubMed:19589339"
FT MUTAGEN 75
FT /note="R->K: Does not impair antimicrobial activity against
FT E.coli, E.aerogenes, S.aureus and B.cereus; when associated
FT with K-94. Reduced induction of IL-8 secretion; when
FT associated with K-90."
FT /evidence="ECO:0000269|PubMed:19589339"
FT MUTAGEN 77
FT /note="S->A: Increased interaction with B.antracis
FT lef/lethal factor."
FT /evidence="ECO:0000269|PubMed:22573326"
FT MUTAGEN 83
FT /note="E->R: Enhanced antibacterial activity against both
FT E.coli and S.aureus. Disrupts homodimerization. Enhanced
FT membrane binding and membrane disintegration abilities, as
FT well further increased antibacterial activity; when
FT associated with R-69."
FT /evidence="ECO:0000269|PubMed:25782105"
FT MUTAGEN 85
FT /note="S->R: Enhanced antibacterial activity against both
FT E.coli and S.aureus."
FT /evidence="ECO:0000269|PubMed:25782105"
FT MUTAGEN 86
FT /note="G->R: Enhanced antibacterial activity against both
FT E.coli and S.aureus."
FT /evidence="ECO:0000269|PubMed:25782105"
FT MUTAGEN 88
FT /note="L->A: Reduced interaction with B.antracis lef/lethal
FT factor. Reduced enhancement of S.flexneri infection."
FT /evidence="ECO:0000269|PubMed:22573326,
FT ECO:0000269|PubMed:29858013"
FT MUTAGEN 89
FT /note="Y->A: Disrupts homodimer-formation. Reduced
FT interaction with B.antracis lef/lethal factor and reduced
FT killing of S.aureus. Reduced enhancement of S.flexneri
FT infection."
FT /evidence="ECO:0000269|PubMed:22573326,
FT ECO:0000269|PubMed:29858013"
FT MUTAGEN 90
FT /note="R->A: Does not disrupt homodimer-formation. Reduced
FT enhancement of S.flexneri infection. Impairs antimicrobial
FT activity against E.coli, E.aerogenes, S.aureus and
FT B.cereus; when associated with A-71. Reduced induction of
FT IL-8 secretion; when associated with A-71."
FT /evidence="ECO:0000269|PubMed:19589339,
FT ECO:0000269|PubMed:29858013"
FT MUTAGEN 90
FT /note="R->K: Impairs antimicrobial activity against S.
FT aureus; when associated with K-71. Reduced induction of IL-
FT 8 secretion; when associated with K-71."
FT /evidence="ECO:0000269|PubMed:19589339"
FT MUTAGEN 91
FT /note="L->A: Reduced interaction with B.antracis lef/lethal
FT factor and decreased bactericidal activity against E.coli
FT and S.aureus. Reduced enhancement of S.flexneri infection."
FT /evidence="ECO:0000269|PubMed:22573326,
FT ECO:0000269|PubMed:29858013"
FT MUTAGEN 92
FT /note="C->S: Prohibits tetramer formation; when associated
FT with S-72."
FT /evidence="ECO:0000269|PubMed:23163963"
FT MUTAGEN 93
FT /note="C->S: Prohibits tetramer formation; when associated
FT with S-67."
FT /evidence="ECO:0000269|PubMed:23163963"
FT MUTAGEN 94
FT /note="R->A: Impairs antimicrobial activity against E.coli,
FT E.aerogenes, S.aureus and B.cereus; when associated with A-
FT 75. Reduced induction of IL-8 secretion; when associated
FT with A-75."
FT /evidence="ECO:0000269|PubMed:19589339"
FT MUTAGEN 94
FT /note="R->K: Does not impair antimicrobial activity against
FT E.coli, E.aerogenes, S.aureus and B.cereus; when associated
FT with K-75. Reduced induction of IL-8 secretion; when
FT associated with K-75."
FT /evidence="ECO:0000269|PubMed:19589339"
FT STRAND 65..70
FT /evidence="ECO:0007829|PDB:4RBX"
FT STRAND 76..84
FT /evidence="ECO:0007829|PDB:4RBX"
FT STRAND 87..93
FT /evidence="ECO:0007829|PDB:4RBX"
SQ SEQUENCE 94 AA; 10071 MW; 19B5B00B6BAF90DA CRC64;
MRTIAILAAI LLVALQAQAE SLQERADEAT TQKQSGEDNQ DLAISFAGNG LSALRTSGSQ
ARATCYCRTG RCATRESLSG VCEISGRLYR LCCR
