DEF6_PANTR
ID DEF6_PANTR Reviewed; 100 AA.
AC Q5G860;
DT 29-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2005, sequence version 1.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=Defensin-6;
DE AltName: Full=Defensin, alpha 6;
DE Flags: Precursor;
GN Name=DEFA6;
OS Pan troglodytes (Chimpanzee).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Pan.
OX NCBI_TaxID=9598;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=15494476; DOI=10.1152/physiolgenomics.00150.2004;
RA Patil A., Hughes A.L., Zhang G.;
RT "Rapid evolution and diversification of mammalian alpha-defensins as
RT revealed by comparative analysis of rodent and primate genes.";
RL Physiol. Genomics 20:1-11(2004).
CC -!- FUNCTION: Host-defense peptide that contributes to intestinal innate
CC immunity and mediates homeostasis at mucosal surfaces by forming
CC higher-order oligomers that capture bacteria and prevent microbial
CC invasion of the epithelium (By similarity). After binding to bacterial
CC surface proteins, undergoes ordered self-assembly to form fibril-like
CC nanonets that surround and entangle bacteria and thereby prevent
CC bacterial invasion across the epithelial barrier (By similarity).
CC Entangles and agglutinates Gram-negative bacteria, such as E.coli,
CC S.typhimurium and Y.enterocolitica, and Gram-positive bacteria such as
CC L.monocytogenes, thereby protecting the intestine against invasion by
CC enteric bacterial pathogens (By similarity). Blocks adhesion of
CC C.albicans to intestinal epithelial cells and thereby suppresses fungal
CC invasion of epithelial cells and biofilm formation (By similarity).
CC Under reducing conditions and in an acidic environment similar to the
CC intestinal milieu, exhibits inhibitory activity against anaerobic
CC bacteria such as B.adolescentis, L.acidophilus, and B.breve, as well as
CC B.longum and S.thermophilus, possibly by leading to alterations in
CC bacterial cell envelope structures (By similarity). The disulfide-
CC linked oxidized form exhibits negligible antimicrobial activity against
CC Gram-negative and Gram-positive bacteria, as compared to the enteric
CC defensin DEFA5 (By similarity). {ECO:0000250|UniProtKB:Q01524}.
CC -!- SUBUNIT: Homodimer (By similarity). Self-assembles into higher-order
CC oligomers termed nanonets, fibril-like structures that entrap microbes
CC (By similarity). Self-assembly into nanonets seems to protect against
CC proteolytic digestion in duodenal fluid (By similarity). Interacts with
CC Y.enterocolitica invasin and S.typhimurium fliC/flagellim; the
CC interaction creates an anchoring site for progressive DEFA6 self-
CC assembly into nanonets (By similarity). {ECO:0000250|UniProtKB:Q01524}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q01524}.
CC Cytoplasmic vesicle, secretory vesicle {ECO:0000250|UniProtKB:Q01524}.
CC Note=Stored as propeptide in secretory granules of small intestinal
CC Paneth cells and found in the ileum lumen as mature peptide.
CC {ECO:0000250|UniProtKB:Q01524}.
CC -!- PTM: Proteolytically cleaved by trypsin at Arg-68; the propeptide is
CC stored in the tissue of the small intestine and the mature peptide is
CC found in the luminal fluid; cleavage may occur during or after release
CC into the lumen (By similarity). The N-terminal propeptide region
CC suppresses self-assembly and renders DEFA6 propeptide unable to
CC agglutinate bacteria and protect human epithelial cells from bacterial
CC invasion (By similarity). {ECO:0000250|UniProtKB:Q01524}.
CC -!- PTM: Under reducing conditions, naturally present in the gut owing to
CC the low redox potential or enzymatically generated by the thioredoxin
CC system, the disulfide bridges are opened leading to a conformational
CC change of DEF6, thereby changing its antimicrobial spectrum (By
CC similarity). The reduced form exhibits inhibitory activity against
CC anaerobic bacteria, in contrast to the minimal antimicrobial activity
CC of the disulfide-linked oxidized form (By similarity). The formation of
CC higher-order nanonets and bacterial entrapment is independent of the
CC redox state (By similarity). {ECO:0000250|UniProtKB:Q01524}.
CC -!- SIMILARITY: Belongs to the alpha-defensin family. {ECO:0000305}.
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DR EMBL; AY746440; AAW78343.1; -; mRNA.
DR RefSeq; NP_001029079.1; NM_001033907.1.
DR AlphaFoldDB; Q5G860; -.
DR SMR; Q5G860; -.
DR Ensembl; ENSPTRT00000089437; ENSPTRP00000086584; ENSPTRG00000051516.
DR GeneID; 619354; -.
DR KEGG; ptr:619354; -.
DR CTD; 1671; -.
DR VGNC; VGNC:50325; DEFA6.
DR GeneTree; ENSGT00940000153268; -.
DR InParanoid; Q5G860; -.
DR OMA; SCHFLER; -.
DR OrthoDB; 1550991at2759; -.
DR Proteomes; UP000002277; Chromosome 8.
DR GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR GO; GO:0005796; C:Golgi lumen; IEA:UniProt.
DR GO; GO:0030133; C:transport vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0042803; F:protein homodimerization activity; IEA:Ensembl.
DR GO; GO:0019731; P:antibacterial humoral response; IBA:GO_Central.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IBA:GO_Central.
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; IBA:GO_Central.
DR GO; GO:0002227; P:innate immune response in mucosa; IBA:GO_Central.
DR GO; GO:0031640; P:killing of cells of another organism; IEA:UniProtKB-KW.
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 3: Inferred from homology;
KW Antibiotic; Antimicrobial; Cytoplasmic vesicle; Defensin; Disulfide bond;
KW Fungicide; Reference proteome; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT PROPEP 20..68
FT /evidence="ECO:0000250|UniProtKB:Q01524"
FT /id="PRO_0000006792"
FT PEPTIDE ?69..100
FT /note="Defensin-6"
FT /evidence="ECO:0000250|UniProtKB:Q01524"
FT /id="PRO_0000006793"
FT DISULFID 72..99
FT /evidence="ECO:0000250|UniProtKB:Q01524"
FT DISULFID 74..88
FT /evidence="ECO:0000250|UniProtKB:Q01524"
FT DISULFID 78..98
FT /evidence="ECO:0000250|UniProtKB:Q01524"
SQ SEQUENCE 100 AA; 10989 MW; EDF63A463C98A7D5 CRC64;
MRTLTILTAV LLVALQAKAE PLQAEDEPLQ AKAYEADAQE QRGANDQDFA VSFAEDASSS
LRALGSTRAF TCHCRRSCYS TEYSYGTCTV MGINHRFCCL
