Defensin beta 4A

1E4Q, 1FD3, 1FD4, 1FQQ

Defensin beta 4A
DEFB4A
Identifiers
AliasesDEFB4A, BD-2, DEFB-2, DEFB102, DEFB2, DEFB4, HBD-2, SAP1, Beta-defensin 2, defensin beta 4A
External IDsOMIM: 602215; GeneCards: DEFB4A
Available structures
PDBHuman UniProt search: PDBe RCSB
Orthologs
DatabasesNCBI: entry; OMA: entry
SpeciesHumanMouse
Entrez

1673

n/a

Ensembl

ENSG00000285181
ENSG00000171711

n/a

UniProt

O15263

n/a

RefSeq (mRNA)

NM_004942

n/a

RefSeq (protein)

NP_001192195
NP_004933

n/a

Location (UCSC)Chr 8: 7.89 – 7.9 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

Defensin beta 4A, also commonly known as beta-defensin 2 (BD-2), is a peptide that in humans is encoded by the gene DEFB4A (previously DEFB4 or DEFB2).[3][4] The nearby gene, DEFB4B (previously DEFB4P),[5] encodes an identical protein in the human reference genome (GRCh38).[3] Defensin beta 4A has been referred to by various other names, including skin-antimicrobial peptide 1 (SAP1)[3] and defensin, beta 4.[6]

Human Defensin beta 4A is a cysteine-rich cationic low molecular weight antimicrobial peptide discovered in lesional skin.

Structure

The DEFB4A protein has a primary structure is made by 64 amino acids. At concentrations ≤2.4 mM, DEFB4A is monomeric.[7] The structure is amphiphilic with a nonuniform surface distribution of positive charge and contains several key structural elements, including a triple-stranded, antiparallel beta sheet with strands 2 and 3 in a beta hairpin conformation. The determination of other structural elements depends on the technique used. When X-ray crystallography is used an alpha helix can be observed at the N-terminal end of the protein (PDB codes: 1fd3​,1fd4​, and 6cs9​). When using NMR this alpha-helix does not appear (PDB code: 1e4q​), however this structure was determined using a truncated version of DEFB4A which was missing the initial 4 amino acids, and may be the reason for the discrepancy.

Gene duplicates

In humans, DEFB4A and a collection of related genes (DEFB103A, DEFB104A, DEFB105A, DEFB106A, DEFB107A, and SPAG11A) are located on a frequently duplicated region of chromosome 8.[8] Due to this, individuals typically have between 2 and 7 diploid copies of defensin beta 4-coding genes.[8] A slight majority (56%) of alleles have 2 copies, resulting in a mode of about 40% of people having a combined 4 diploid copies.[8] Similar polymorphic duplications are also seen in certain alpha defensin genes and in other species.[8]

Function

Defensins form a family of microbicidal and cytotoxic peptides made by neutrophils. Members of the defensin family are highly similar in protein sequence. DEFB4A is an antibiotic peptide which is locally regulated by inflammation.[9]

Human defensin beta 4A is produced by a number of epithelial cells and exhibits potent antimicrobial activity against Gram-negative bacteria and Candida, but not Gram-positive S. aureus. It has been speculated that DEFB4A may contribute to the infrequency of Gram-negative infections on skin and lung tissue.[10]

Defensin beta 4A represents the first human defensin that is produced following stimulation of epithelial cells by contact with microorganisms such as P. aeruginosa or cytokines such as TNF-alpha and IL-1 beta. The DEFB4A gene and protein are locally expressed in keratinocytes associated with inflammatory skin lesions. It is intriguing to speculate that DEFB4A is a dynamic component of the local epithelial defense system of the skin and respiratory tract having a role to protect surfaces from infection, and providing a possible reason why skin and lung infections with Gram-negative bacteria are rather rare.[10]

Although this protein doesn’t have any antibacterial activity against Gram-positive bacteria, there is a study showing that there is a synergy between DEFB4A and other proteins.[11] One example of this synergistic effect is with epiP, a protein segregated by some strains of S. epidermidis. DEFB4A, holding hands with epiP, is capable of killing S. aureus, a Gram-positive bacteria responsible of human diseases.

References

  1. ^ a b c ENSG00000171711 GRCh38: Ensembl release 89: ENSG00000285181, ENSG00000171711 – Ensembl, May 2017
  2. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. ^ a b c "Defensin beta 4A". uniprot.org. UniProt consortium. Retrieved 2026-07-29.
  4. ^ Harder J, Bartels J, Christophers E, Schröder JM (June 1997). "A peptide antibiotic from human skin". Nature. 387 (6636): 861. Bibcode:1997Natur.387..861H. doi:10.1038/43088. PMID 9202117. S2CID 4354862.
  5. ^ "DEFB4B defensin beta 4B [Homo sapiens (human)]". ncbi.nlm.nih.gov. Retrieved 2026-08-13.
  6. ^ "DEFB4A defensin beta 4A [ Homo sapiens (human) ]". ncbi.nlm.nih.gov. Retrieved 2026-08-13.
  7. ^ Sawai MV, Jia HP, Liu L, Aseyev V, Wiencek JM, McCray PB, Ganz T, Kearney WR, Tack BF (April 2001). "The NMR structure of human beta-defensin-2 reveals a novel alpha-helical segment". Biochemistry. 40 (13): 3810–3816. doi:10.1021/bi002519d. PMID 11300761.
  8. ^ a b c d Hollox EJ, Abujaber R (2027-08-10). "Evolution and diversity of defensins in vertebrates". InEvolutionary biology: self/nonself evolution, species and complex traits evolution, methods and concepts. 10. Springer International Publishing: 27–50. doi:10.1007/978-3-319-61569-1_2.
  9. ^ "Entrez Gene: DEFB4 defensin, beta 4".
  10. ^ a b Schröder JM, Harder J (June 1999). "Human beta-defensin-2". The International Journal of Biochemistry & Cell Biology. 31 (6): 645–651. doi:10.1016/S1357-2725(99)00013-8. PMID 10404637.
  11. ^ Iwase T, Uehara Y, Shinji H, Tajima A, Seo H, Takada K, Agata T, Mizunoe Y (May 2010). "Staphylococcus epidermidis Esp inhibits Staphylococcus aureus biofilm formation and nasal colonization". Nature. 465 (7296): 346–349. Bibcode:2010Natur.465..346I. doi:10.1038/nature09074. PMID 20485435. S2CID 4392908.

Further reading

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