DEFA6
entrez
1671
canonical
uniprot
Q01524
canonical
ensembl
ENSG00000164822
resolver
ensembl
ENSG00000285136
resolver
ensp
ENSP00000297436
resolver
ensp
ENSP00000494361
resolver
enst
ENST00000297436
resolver
enst
ENST00000646187
resolver
genesymbol
DEFA6
resolver
genesymbol_syn
DEF6
resolver
hgnc
HGNC:2765
resolver
uniprot
Q6EZF9
resolver
uniprot_entry
DEF6_HUMAN
resolver
uniprot_sec
Q6EZF9
resolver
amino_acid_sequence
MRTLTILTAVLLVALQAKAEPLQAEDDPLQAKAYEADAQEQRGANDQDFAVSFAEDASSSLRALGSTRAFTCHCRRSCYSTEYSYGTCTVMGINHRFCCL
uniprot
proteins
function
FUNCTION: Host-defense peptide that contributes to intestinal innate immunity and mediates homeostasis at mucosal surfaces by forming higher-order oligomers that capture bacteria and prevent microbial invasion of the epithelium (PubMed:15616305, PubMed:17088326, PubMed:25158166, PubMed:25354318, PubMed:28026958). After binding to bacterial surface proteins, undergoes ordered self-assembly to form fibril-like nanonets that surround and entangle bacteria and thereby prevent bacterial invasion across the epithelial barrier (PubMed:22722251). Entangles and agglutinates Gram-negative bacteria, such as E.coli, S.typhimurium and Y.enterocolitica, and Gram-positive bacteria such as L.monocytogenes, thereby protecting the intestine against invasion by enteric bacterial pathogens (PubMed:22722251, PubMed:25158166, PubMed:27076903). Blocks adhesion of C.albicans to intestinal epithelial cells and thereby suppresses fungal invasion of epithelial cells and biofilm formation (PubMed:28026958). Under reducing conditions and in an acidic environment similar to the intestinal milieu, exhibits inhibitory activity against anaerobic bacteria such as B.adolescentis, L.acidophilus and B.breve, as well as B.longum and S.thermophilus, possibly by leading to alterations in bacterial cell envelope structures (PubMed:25354318). The disulfide-linked oxidized form exhibits negligible antimicrobial activity against Gram-negative and Gram-positive bacteria, as compared to the enteric defensin DEFA5 (PubMed:15616305, PubMed:17088326). {ECO:0000269|PubMed:15616305, ECO:0000269|PubMed:17088326, ECO:0000269|PubMed:22722251, ECO:0000269|PubMed:25158166, ECO:0000269|PubMed:25354318, ECO:0000269|PubMed:27076903, ECO:0000269|PubMed:28026958}.
uniprot
proteins
mass_dalton
10975
uniprot
proteins
mutagenesis
MUTAGEN 70; /note="F->A: Abrogates self-assembly to fibrils and attenuates agglutination of bacteria and prevention of L.monocytogenes invasion. Fails to block intestinal cell adhesion and biofilm formation of C.albicans."; /evidence="ECO:0000269|PubMed:25158166, ECO:0000269|PubMed:28026958"; MUTAGEN 90; /note="V->T: Perturbs self-assembly to fibrils and reduces agglutination of bacteria."; /evidence="ECO:0000269|PubMed:25158166"; MUTAGEN 93; /note="I->T: Perturbs self-assembly to fibrils and reduces agglutination of bacteria."; /evidence="ECO:0000269|PubMed:25158166"; MUTAGEN 95; /note="H->A: Does not impact fibril formation or agglutination of bacteria."; /evidence="ECO:0000269|PubMed:25158166"; MUTAGEN 95; /note="H->W: Perturbs self-assembly to fibrils and reduces agglutination of bacteria. Does not abolish antimicrobial activity against B.adolescentis and formation of extracellular net-like structures (under reducing conditions)."; /evidence="ECO:0000269|PubMed:22722251, ECO:0000269|PubMed:25158166, ECO:0000269|PubMed:25354318"; MUTAGEN 97; /note="F->A: Abrogates self-assembly to fibrils and attenuates agglutination of bacteria and prevention of L.monocytogenes invasion."; /evidence="ECO:0000269|PubMed:25158166
uniprot
proteins
post_translational_modification
PTM: Proteolytically cleaved by trypsin at Arg-68; the propeptide is stored in the tissue of the small intestine and the mature peptide is found in the luminal fluid; cleavage may occur during or after release into the lumen (PubMed:27076903). The N-terminal propeptide region suppresses self-assembly and renders DEFA6 propeptide unable to agglutinate bacteria and protect human epithelial cells from bacterial invasion (PubMed:27076903). {ECO:0000269|PubMed:27076903}.; PTM: Under reducing conditions, naturally present in the gut owing to the low redox potential or enzymatically generated by the thioredoxin system, the disulfide bridges are opened leading to a conformational change of DEF6, thereby changing its antimicrobial spectrum (PubMed:25354318). The reduced form exhibits inhibitory activity against anaerobic bacteria, in contrast to the minimal antimicrobial activity of the disulfide-linked oxidized form (PubMed:15616305, PubMed:17088326, PubMed:25354318). The formation of higher-order nanonets and bacterial entrapment is independent of the redox state (PubMed:30808760). {ECO:0000269|PubMed:15616305, ECO:0000269|PubMed:17088326, ECO:0000269|PubMed:25354318, ECO:0000269|PubMed:30808760}.
uniprot
proteins
protein_family
Alpha-defensin family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15616305
uniprot
proteins
pubmed
16421571
uniprot
proteins
pubmed
17088326
uniprot
proteins
pubmed
22722251
uniprot
proteins
pubmed
25158166
uniprot
proteins
pubmed
25354318
uniprot
proteins
pubmed
27076903
uniprot
proteins
pubmed
28026958
uniprot
proteins
pubmed
30808760
uniprot
proteins
pubmed
8417977
uniprot
proteins
pubmed
8626737
uniprot
proteins
sequence_length
100
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:27076903}. Cytoplasmic vesicle, secretory vesicle {ECO:0000269|PubMed:27076903}. Note=Stored as propeptide in secretory granules of small intestinal Paneth cells and found in the ileum lumen as mature peptide. {ECO:0000269|PubMed:27076903}.
uniprot
proteins