Neutrophil defensin 1 (DEFA1B)
The protein contains 94 amino acids for an estimated molecular weight of 10201 Da.
Defensin 1 and defensin 2 have antibacterial, fungicide and antiviral activities. Has antimicrobial activity against Gram-negative and Gram-positive bacteria. Defensins are thought to kill microbes by permeabilizing their plasma membrane. (updated: Jan. 7, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Antibacterial humoral response
Antimicrobial humoral immune response mediated by antimicrobial peptide
Antimicrobial humoral response
Cellular response to lipopolysaccharide
Chemotaxis
Defense response to fungus
Defense response to Gram-negative bacterium
Defense response to Gram-positive bacterium
Defense response to protozoan
Defense response to virus
Disruption by host of symbiont cells
Immune response
Innate immune response
Innate immune response in mucosa
Intracellular estrogen receptor signaling pathway
Killing by host of symbiont cells
Killing of cells of other organism
Membrane disruption in other organism
Neutrophil degranulation
Pore formation in membrane of other organism during symbiotic interaction
T cell chemotaxis
Cellular Component
Azurophil granule lumen
Collagen-containing extracellular matrix
Extracellular exosome
Extracellular matrix
Extracellular region
Extracellular space
Golgi lumen
Molecular Function
The reference OMIM entry for this protein is 125220
Defensin, alpha, 1; defa1
Defensin 1; def1
Human neutrophil peptide 1; hnp1
Myeloid-related sequence; mrs defensin, alpha, 2, included; defa2, included
Human neutrophil peptide 2, included; hnp2, included
Cryptdin, included
Retrocyclin, i
CLONING
Defensins are a group of microbicidal and cytotoxic peptides made by neutrophils. Daher et al. (1988) stated that 3 human defensins, also called human neutrophil peptide-1 (HNP1), HNP2, and HNP3 (604522), make up about 30% of the neutrophil's total granule protein. From a human promyelocytic leukemia cDNA library, Daher et al. (1988) isolated clones encoding HNP1 and HNP3. Analysis of these clones indicated that the defensins are made as 94-amino acid precursor proteins that must be cleaved to yield the mature peptides. Mature HNP1 and HNP3 contain 30 amino acids each and are identical except for the N-terminal amino acid. HNP2 may be formed by degradation or processing of HNP1 and/or HNP3, because it lacks this N-terminal amino acid and is otherwise identical to HNP1 and HNP3. Defensin mRNA was detected in normal bone marrow cells but not in peripheral blood leukocytes. Mars et al. (1987, 1988) isolated 2 overlapping cDNA clones that represent an mRNA that is highly expressed in selected subpopulations of myeloid leukocytes. The nucleotide sequence indicated that this myeloid-related sequence (MRS) probably encodes a unique 93-amino acid protein, including a leader sequence of 18 amino acids.GENE FUNCTION
Liu et al. (1997) reported that there are 7 defensins in humans: 6 alpha-defensins and a beta-defensin (DEFB1; 602056). Neutrophil alpha-defensins 1 to 4 (DEFA4; 601157) are found in the microbicidal granules of neutrophils (Ganz and Lehrer, 1995) and alpha-defensins 5 (DEFA5; 600472) and 6 (DEFA6; 600471) are located in Paneth cells of the intestinal tract. DEFB1 appears to be involved in the antimicrobial defense of the epithelia of surfaces such as those of the respiratory tract, urinary tract, and vagina. In human airways, epithelial cells lining the lumen, and intraluminal cells (e.g., polymorphonucleus cells) participate in the innate immune response. These cells secrete or express on their surfaces arginine-specific ADP ribosyltransferases. Defensins, antimicrobial proteins secreted by immune cells, are arginine-rich, leading Paone et al. (2002) to hypothesize that ADP ribosylation could modify their biologic activities. They found that an arginine-specific ADP ribosyltransferase-1 present on airway epithelial cells modifies arg-14 of alpha-defensin-1. ADP-ribosylated defensin-1 had decreased antimicrobial and cytotoxic activities but still stimulated T-cell chemotaxis and IL8 release from A549 cells. Further, ADP-ribosylated defensin-1 inhibited cytotoxic and antimicrobial activities of unmodified defensin-1. Paone et al. (2002) identified ADP-ribosylated defensin-1 in bronchoalveolar lavage fluid from smokers but not from nonsmokers, confirming its existence in vivo. Thus, airway mono-ADP-ribosyltransferases could have an important regulatory role in the innate immune response through modification of alpha-defensin-1 and perhaps other basic molecules, with alteration of their biologic properties. The human alpha- and beta-defensin genes cluster on 8p23, a locus that also contains the pseudogene for retrocyclin. Cole et al. (2002) reported that human bone marrow expresses mRNA that is homologous to the precursors of rhesus monkey circular minidefensins. Although a stop codon within its signal sequence suggested that the human transcript now represents an expressed pseudogene, they used its sequence and information derived from studies on rhesus monkeys to synthesize retrocyclin, the putative ance ... More on the omim web site
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
March 25, 2017: Additional information
No protein expression data in P. Mayeux work for DEFA1B
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 125220 was added.
Sept. 16, 2015: Protein entry updated
Automatic update: model status changed