DEF3_HUMAN
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 03-AUG-2022, entry version 153.
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 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 [11]
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 [12]
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: Defensin 2 and defensin 3 have antibiotic, fungicide and
CC antiviral activities. Has antimicrobial activity against Gram-negative
CC and Gram-positive bacteria. Defensins are thought to kill microbes by
CC permeabilizing their plasma membrane. {ECO:0000269|PubMed:15616305,
CC ECO:0000269|PubMed:15894545, ECO:0000269|PubMed:17452329,
CC ECO:0000269|PubMed:2006422}.
CC -!- SUBUNIT: Dimer. {ECO:0000269|PubMed:17452329,
CC ECO:0000269|PubMed:2006422}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- SIMILARITY: Belongs to the alpha-defensin family. {ECO:0000305}.
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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 IntAct; P59666; 2.
DR STRING; 9606.ENSP00000328359; -.
DR iPTMnet; P59666; -.
DR PhosphoSitePlus; P59666; -.
DR BioMuta; DEFA3; -.
DR DMDM; 30316323; -.
DR jPOST; P59666; -.
DR MassIVE; P59666; -.
DR PaxDb; P59666; -.
DR PeptideAtlas; P59666; -.
DR PRIDE; P59666; -.
DR ProteomicsDB; 57155; -.
DR TopDownProteomics; P59666; -.
DR Antibodypedia; 22005; 154 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 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; IRVHENF; -.
DR OrthoDB; 1610714at2759; -.
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 199 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 tissues.
DR ExpressionAtlas; P59666; baseline and differential.
DR Genevisible; P59666; HS.
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: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 GO; GO:0051673; P:membrane disruption in another organism; IBA:GO_Central.
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; 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
