Beta-defensin 2

Mammalian protein found in humans

DEFB4B

Available structures

PDB

Human UniProt search: PDBe RCSB

List of PDB id codes
1E4Q, 1FD3, 1FD4, 1FQQ

Identifiers

Aliases

DEFB4B, DEFB4P, defensin beta 4B

External IDs

HomoloGene: 122147; GeneCards: DEFB4B; OMA:DEFB4B - orthologs

Gene location (Human)

Chr.	Chromosome 8 (human)^[1]

Band	8p23.1	Start	7,414,855 bp^[1]
Band	8p23.1	End	7,416,863 bp^[1]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

gastric mucosa

muscle tissue

tonsil

mucosa of esophagus

islet of Langerhans

cell

urinary bladder

olfactory zone of nasal mucosa

somatic cell

monocyte

n/a

More reference expression data

BioGPS

n/a

Gene ontology
Molecular function	protein binding CCR6 chemokine receptor binding chemoattractant activity
Cellular component	Golgi lumen extracellular region extracellular space intracellular anatomical structure
Biological process	G protein-coupled receptor signaling pathway defense response immune response chemotaxis defense response to Gram-negative bacterium defense response to bacterium defense response to Gram-positive bacterium antimicrobial humoral response antimicrobial humoral immune response mediated by antimicrobial peptide positive chemotaxis cell chemotaxis
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


100289462


n/a

Ensembl


ENSG00000177257 ENSG00000275444 ENSG00000285433


n/a

UniProt


O15263


n/a

RefSeq (mRNA)


NM_001205266


n/a

RefSeq (protein)


NP_001192195 NP_004933


n/a

Location (UCSC)

Chr 8: 7.41 – 7.42 Mb

n/a

PubMed search

^[2]

n/a

Wikidata

View/Edit Human

Beta-defensin 2 (BD-2) also known as skin-antimicrobial peptide 1 (SAP1) is a peptide that in humans is encoded by the DEFB4 (defensin, beta 4) gene.^[3]

Human beta-defensin-2 (hBD-2) is a cysteine-rich cationic low molecular weight antimicrobial peptide discovered in lesional skin.

Structure

hBD-2 is a protein whose primary structure is made by 64 aminoacids. At concentrations ≤2.4 mM, hBD-2 is monomeric.^[4] 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 hBD-2 which was missing the initial 4 amino acids, and may be the reason for the discrepancy.

Function

Defensins form a family of microbicidal and cytotoxic peptides made by neutrophils. Members of the defensin family are highly similar in protein sequence. Beta-defensin 2 is an antibiotic peptide which is locally regulated by inflammation.^[5]

Human beta-defensin 2 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 beta-defensin 2 may contribute to the infrequency of Gram-negative infections on skin and lung tissue.^[6]

hBD-2 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 HBD-2 gene and protein are locally expressed in keratinocytes associated with inflammatory skin lesions. It is intriguing to speculate that HBD-2 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.^[6]

Although this protein doesn’t have any antibacterial activity against Gram-positive bacteria, there is a study showing that there is a synergy between hBD-2 and other proteins.^[7] One example of this synergistic effect is with epiP, a protein segregated by some strains of S. epidermidis. hBD2, holding hands with epiP, is capable of killing S. aureus, a Gram-positive bacteria responsible of human diseases.

References

^ ^a ^b ^c ENSG00000275444, ENSG00000285433 GRCh38: Ensembl release 89: ENSG00000177257, ENSG00000275444, ENSG00000285433 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Harder J, Bartels J, Christophers E, Schröder JM (June 1997). "A peptide antibiotic from human skin". Nature. 387 (6636): 861. doi:10.1038/43088. PMID 9202117. S2CID 4354862.
^ 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.
^ "Entrez Gene: DEFB4 defensin, beta 4".
^ ^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.
^ 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.