ID DEF3_HUMAN Reviewed; 94 AA. AC P59666; P11479; Q14125; DT 30-APR-2003, integrated into UniProtKB/Swiss-Prot. DT 30-APR-2003, sequence version 1. DT 27-MAR-2024, entry version 162. DE RecName: Full=Neutrophil defensin 3; DE AltName: Full=Defensin, alpha 3; DE AltName: Full=HNP-3; DE Short=HP-3; DE Short=HP3; DE Contains: DE RecName: Full=HP 3-56; DE Contains: DE RecName: Full=Neutrophil defensin 2; DE AltName: Full=HNP-2; DE Short=HP-2; DE Short=HP2; DE Flags: Precursor; GN Name=DEFA3; Synonyms=DEF3; 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]. RX PubMed=3174637; DOI=10.1073/pnas.85.19.7327; RA Daher K.A., Lehrer R.I., Ganz T., Kronenberg M.; RT "Isolation and characterization of human defensin cDNA clones."; RL Proc. Natl. Acad. Sci. U.S.A. 85:7327-7331(1988). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=2918759; RA Wiedemann L.M., Francis G.E., Lamb R.F., Burns J.H., Winnie J.N., RA McKenzie E.D., Birnie G.D.; RT "Differentiation stage-specific expression of a gene during RT granulopoiesis."; RL Leukemia 3:227-234(1989). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=8477861; DOI=10.1016/0014-5793(93)80122-b; RA Linzmeier R., Michaelson D., Liu L., Ganz T.; RT "The structure of neutrophil defensin genes."; RL FEBS Lett. 321:267-273(1993). RN [4] RP ERRATUM OF PUBMED:8477861. RX PubMed=8325384; DOI=10.1016/0014-5793(93)81813-f; RA Linzmeier R., Michaelson D., Liu L., Ganz T.; RL FEBS Lett. 326:299-300(1993). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Pancreas, and Spleen; 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 [6] RP PROTEIN SEQUENCE OF 65-94. RX PubMed=4056036; DOI=10.1172/jci112121; RA Selsted M.E., Harwig S.S.L., Ganz T., Schilling J.W., Lehrer R.I.; RT "Primary structures of three human neutrophil defensins."; RL J. Clin. Invest. 76:1436-1439(1985). RN [7] RP DISULFIDE BONDS. RX PubMed=2917986; DOI=10.1016/s0021-9258(19)84952-9; RA Selsted M.E., Harwig S.S.L.; RT "Determination of the disulfide array in the human defensin HNP-2. A RT covalently cyclized peptide."; RL J. Biol. Chem. 264:4003-4007(1989). RN [8] RP PROTEOLYTIC PROCESSING. RX PubMed=1339298; RA Valore E.V., Ganz T.; RT "Posttranslational processing of defensins in immature human myeloid RT cells."; RL Blood 79:1538-1544(1992). RN [9] 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 [10] RP FUNCTION. RX PubMed=15772169; DOI=10.1073/pnas.0500508102; RA Kim C., Gajendran N., Mittruecker H.W., Weiwad M., Song Y.H., Hurwitz R., RA Wilmanns M., Fischer G., Kaufmann S.H.; RT "Human alpha-defensins neutralize anthrax lethal toxin and protect against RT its fatal consequences."; RL Proc. Natl. Acad. Sci. U.S.A. 102:4830-4835(2005). RN [11] RP INTERACTION WITH HERPES VIRUS 1 ENVELOPE GLYCOPROTEIN B (MICROBIAL RP INFECTION), AND FUNCTION. RX PubMed=17142766; DOI=10.4049/jimmunol.177.12.8658; RA Hazrati E., Galen B., Lu W., Wang W., Ouyang Y., Keller M.J., Lehrer R.I., RA Herold B.C.; RT "Human alpha- and beta-defensins block multiple steps in herpes simplex RT virus infection."; RL J. Immunol. 177:8658-8666(2006). RN [12] RP FUNCTION. RX PubMed=18435932; DOI=10.1053/j.gastro.2008.03.008; RA Giesemann T., Guttenberg G., Aktories K.; RT "Human alpha-defensins inhibit Clostridium difficile toxin B."; RL Gastroenterology 134:2049-2058(2008). RN [13] RP FUNCTION. RX PubMed=25963798; DOI=10.1111/lam.12438; RA Cardot-Martin E., Casalegno J.S., Badiou C., Dauwalder O., Keller D., RA Prevost G., Rieg S., Kern W.V., Cuerq C., Etienne J., Vandenesch F., RA Lina G., Dumitrescu O.; RT "alpha-Defensins partially protect human neutrophils against Panton- RT Valentine leukocidin produced by Staphylococcus aureus."; RL Lett. Appl. Microbiol. 61:158-164(2015). RN [14] RP SUBCELLULAR LOCATION. RX PubMed=29282039; DOI=10.1186/s12890-017-0558-4; RA Liu X., Chen Q., Luo Y., Hu Y., Lai D., Zhang X., Zhang X., Yu J., Fang X., RA Shu Q.; RT "Plasma levels of alarmin HNPs 1-3 associate with lung dysfunction after RT cardiac surgery in children."; RL BMC Pulm Med 17:218-218(2017). RN [15] RP X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF DEFENSIN 3, SUBUNIT, AND FUNCTION. RX PubMed=2006422; DOI=10.1126/science.2006422; RA Hill C.P., Yee J., Selsted M.E., Eisenberg D.; RT "Crystal structure of defensin HNP-3, an amphiphilic dimer: mechanisms of RT membrane permeabilization."; RL Science 251:1481-1485(1991). RN [16] RP X-RAY CRYSTALLOGRAPHY (1.15 ANGSTROMS) OF 66-94, DISULFIDE BONDS, AND RP FUNCTION. RX PubMed=15894545; DOI=10.1074/jbc.m503084200; RA Xie C., Prahl A., Ericksen B., Wu Z., Zeng P., Li X., Lu W.-Y., RA Lubkowski J., Lu W.; RT "Reconstruction of the conserved beta-bulge in mammalian defensins using D- RT amino acids."; RL J. Biol. Chem. 280:32921-32929(2005). RN [17] RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS) OF 65-94, FUNCTION, AND SUBUNIT. RX PubMed=17452329; DOI=10.1074/jbc.m611003200; RA Zou G., de Leeuw E., Li C., Pazgier M., Li C., Zeng P., Lu W.-Y., RA Lubkowski J., Lu W.; RT "Toward understanding the cationicity of defensins. Arg and Lys versus RT their noncoded analogs."; RL J. Biol. Chem. 282:19653-19665(2007). CC -!- FUNCTION: Effector molecule of the innate immune system that acts via CC antibiotic-like properties against a broad array of infectious agents CC including bacteria, fungi, and viruses (PubMed:15616305, CC PubMed:15772169, PubMed:17142766). Possesses the ability to neutralize CC bacterial toxins such as B. anthracis lethal factor, Clostridium CC difficile cytotoxin B as well as leukocidin produced by Staphylococcus CC aureus (PubMed:15772169, PubMed:18435932, PubMed:25963798). Blocks also CC herpes simplex virus infection by interacting with envelope CC glycoprotein B and thus preventing its binding to heparan sulfate, the CC receptor for attachment (PubMed:17142766). CC {ECO:0000269|PubMed:15616305, ECO:0000269|PubMed:15772169, CC ECO:0000269|PubMed:15894545, ECO:0000269|PubMed:17142766, CC ECO:0000269|PubMed:17452329, ECO:0000269|PubMed:18435932, CC ECO:0000269|PubMed:2006422, ECO:0000269|PubMed:25963798}. CC -!- SUBUNIT: Dimer. {ECO:0000269|PubMed:17452329, CC ECO:0000269|PubMed:2006422}. CC -!- SUBUNIT: (Microbial infection) Interacts with herpes virus 1 HHV-1 CC envelope glycoprotein B; this interaction inhibits viral infection. CC {ECO:0000269|PubMed:17142766}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:29282039}. CC -!- SIMILARITY: Belongs to the alpha-defensin family. {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M21131; AAA35753.2; -; mRNA. DR EMBL; M23281; AAA52304.1; -; mRNA. DR EMBL; L12691; AAB57722.1; -; Genomic_DNA. DR EMBL; X13621; CAA31952.1; -; mRNA. DR EMBL; BC027917; AAH27917.1; -; mRNA. DR CCDS; CCDS5962.1; -. DR PIR; C40499; C40499. DR RefSeq; NP_005208.1; NM_005217.3. DR PDB; 1DFN; X-ray; 1.90 A; A/B=65-94. DR PDB; 1ZMH; X-ray; 1.50 A; A/B/C/D=66-94. DR PDB; 1ZMI; X-ray; 1.15 A; A/B/C/D=66-94. DR PDB; 1ZMK; X-ray; 1.30 A; A/B=66-94. DR PDB; 2PM4; X-ray; 1.95 A; A/B=65-94. DR PDB; 2PM5; X-ray; 2.40 A; A/B=65-94. DR PDBsum; 1DFN; -. DR PDBsum; 1ZMH; -. DR PDBsum; 1ZMI; -. DR PDBsum; 1ZMK; -. DR PDBsum; 2PM4; -. DR PDBsum; 2PM5; -. DR AlphaFoldDB; P59666; -. DR BMRB; P59666; -. DR SMR; P59666; -. DR BioGRID; 108032; 2. DR IntAct; P59666; 2. DR STRING; 9606.ENSP00000328359; -. DR GlyGen; P59666; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P59666; -. DR PhosphoSitePlus; P59666; -. DR BioMuta; DEFA3; -. DR DMDM; 30316323; -. DR jPOST; P59666; -. DR MassIVE; P59666; -. DR PaxDb; 9606-ENSP00000328359; -. DR PeptideAtlas; P59666; -. DR PRIDE; P59666; -. DR ProteomicsDB; 57155; -. DR Pumba; P59666; -. DR TopDownProteomics; P59666; -. DR Antibodypedia; 22005; 181 antibodies from 24 providers. DR DNASU; 1668; -. DR Ensembl; ENST00000327857.7; ENSP00000328359.2; ENSG00000239839.7. DR GeneID; 1668; -. DR KEGG; hsa:1668; -. DR MANE-Select; ENST00000327857.7; ENSP00000328359.2; NM_005217.4; NP_005208.1. DR AGR; HGNC:2762; -. DR CTD; 1668; -. DR DisGeNET; 1668; -. DR GeneCards; DEFA3; -. DR HGNC; HGNC:2762; DEFA3. DR HPA; ENSG00000239839; Tissue enriched (bone). DR MIM; 604522; gene. DR neXtProt; NX_P59666; -. DR OpenTargets; ENSG00000239839; -. DR PharmGKB; PA27239; -. DR VEuPathDB; HostDB:ENSG00000239839; -. DR eggNOG; ENOG502T2EX; Eukaryota. DR GeneTree; ENSGT00940000153268; -. DR InParanoid; P59666; -. DR OMA; CHCSRTF; -. DR OrthoDB; 4739623at2759; -. DR PhylomeDB; P59666; -. DR TreeFam; TF338414; -. DR PathwayCommons; P59666; -. DR Reactome; R-HSA-1461973; Defensins. DR Reactome; R-HSA-1462054; Alpha-defensins. DR SignaLink; P59666; -. DR BioGRID-ORCS; 1668; 3 hits in 235 CRISPR screens. DR ChiTaRS; DEFA3; human. DR EvolutionaryTrace; P59666; -. DR GeneWiki; DEFA3; -. DR GenomeRNAi; 1668; -. DR Pharos; P59666; Tbio. DR PRO; PR:P59666; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; P59666; Protein. DR Bgee; ENSG00000239839; Expressed in bone marrow and 80 other cell types or tissues. DR ExpressionAtlas; P59666; baseline and differential. DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome. 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:0005796; C:Golgi lumen; TAS:Reactome. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0019731; P:antibacterial humoral response; IDA:UniProtKB. 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; IBA:GO_Central. DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB. DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW. DR GO; GO:0051673; P:disruption of plasma membrane integrity in another organism; IBA:GO_Central. DR GO; GO:0002227; P:innate immune response in mucosa; IDA:UniProtKB. DR GO; GO:0030520; P:intracellular estrogen receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0031640; P:killing of cells of another organism; IDA:UniProtKB. DR InterPro; IPR016327; Alpha-defensin. DR InterPro; IPR006081; Alpha-defensin_C. DR InterPro; IPR002366; Alpha-defensin_N. DR InterPro; IPR006080; Beta/alpha-defensin_C. DR PANTHER; PTHR11876; ALPHA-DEFENSIN 1; 1. DR PANTHER; PTHR11876:SF19; NEUTROPHIL DEFENSIN 1-RELATED; 1. DR Pfam; PF00323; Defensin_1; 1. DR Pfam; PF00879; Defensin_propep; 1. DR PIRSF; PIRSF001875; Alpha-defensin; 1. DR SMART; SM01418; Defensin_propep; 1. DR SMART; SM00048; DEFSN; 1. DR SUPFAM; SSF57392; Defensin-like; 1. DR PROSITE; PS00269; DEFENSIN; 1. DR Genevisible; P59666; HS. PE 1: Evidence at protein level; KW 3D-structure; Antibiotic; Antimicrobial; Antiviral defense; Defensin; KW Direct protein sequencing; Disulfide bond; Fungicide; Reference proteome; KW Secreted; Signal. FT SIGNAL 1..19 FT PROPEP 20..38 FT /id="PRO_0000006777" FT CHAIN 39..94 FT /note="HP 3-56" FT /id="PRO_0000006778" FT PEPTIDE 65..94 FT /note="Neutrophil defensin 3" FT /id="PRO_0000006779" FT PEPTIDE 66..94 FT /note="Neutrophil defensin 2" FT /id="PRO_0000006780" FT DISULFID 66..94 FT DISULFID 68..83 FT DISULFID 73..93 FT STRAND 67..71 FT /evidence="ECO:0007829|PDB:1ZMI" FT STRAND 78..85 FT /evidence="ECO:0007829|PDB:1ZMI" FT STRAND 88..94 FT /evidence="ECO:0007829|PDB:1ZMI" SQ SEQUENCE 94 AA; 10245 MW; 0E0F8E957376C6AF CRC64; MRTLAILAAI LLVALQAQAE PLQARADEVA AAPEQIAADI PEVVVSLAWD ESLAPKHPGS RKNMDCYCRI PACIAGERRY GTCIYQGRLW AFCC //