DEFA1 defensin alpha 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: DEFA1provided by HGNC
Official Full Name: defensin alpha 1provided by HGNC
Primary source: HGNC:HGNC:2761
See related: Ensembl:ENSG00000206047 MIM:125220; AllianceGenome:HGNC:2761
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: HP1; MRS; DEF1; HP-1; DEFA2; HNP-1
Summary: Defensins are a family of antimicrobial and cytotoxic peptides thought to be involved in host defense. They are abundant in the granules of neutrophils and also found in the epithelia of mucosal surfaces such as those of the intestine, respiratory tract, urinary tract, and vagina. Members of the defensin family are highly similar in protein sequence and distinguished by a conserved cysteine motif. The protein encoded by this gene, defensin, alpha 1, is found in the microbicidal granules of neutrophils and likely plays a role in phagocyte-mediated host defense. Several alpha defensin genes are clustered on chromosome 8. This gene differs from defensin, alpha 3 by only one amino acid. This gene and the gene encoding defensin, alpha 3 are both subject to copy number variation. [provided by RefSeq, Oct 2014]
Expression: Restricted expression toward bone marrow (RPKM 27404.8) See more
Orthologs: all
NEW: Try the new Gene table
Try the new Transcript table

Genomic context

Location:: 8p23.1

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	8	NC_000008.11 (6977649..6980092, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	8	NC_060932.1 (6732309..6734752, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	8	NC_000008.10 (6835171..6837614, complement)

Chromosome 8 - NC_000008.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

Go to the top of the page Help

Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

Go to the top of the page Help

See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

Go to the top of the page Help

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Alpha Defensin-1 Biomarker Outperforms Culture in Diagnosing Breast Implant-Related Infection: Results from a Multicenter Prospective Study.
Title: Alpha Defensin-1 Biomarker Outperforms Culture in Diagnosing Breast Implant-Related Infection: Results from a Multicenter Prospective Study.
Inhibition of SARS-CoV-2 Infection by Human Defensin HNP1 and Retrocyclin RC-101.
Title: Inhibition of SARS-CoV-2 Infection by Human Defensin HNP1 and Retrocyclin RC-101.
Elevated Levels of Neutrophil Activated Proteins, Alpha-Defensins (DEFA1), Calprotectin (S100A8/A9) and Myeloperoxidase (MPO) Are Associated With Disease Severity in COVID-19 Patients.
Title: Elevated Levels of Neutrophil Activated Proteins, Alpha-Defensins (DEFA1), Calprotectin (S100A8/A9) and Myeloperoxidase (MPO) Are Associated With Disease Severity in COVID-19 Patients.
Alpha-Defensin versus Leukocyte Esterase in Periprosthetic Joint Infection: An Updated Meta-Analysis.
Title: Alpha-Defensin versus Leukocyte Esterase in Periprosthetic Joint Infection: An Updated Meta-Analysis.
Study in ApoE-/- transgenic mice expressing alpha-def-1 revealed that alpha-def-1 lowers total plasma cholesterol and decreases lesion size. However, lesion size was larger than in mice with total plasma cholesterol lowered to the same extent by inhibiting its adsorption or by ingesting a low-fat diet. alpha-def-1 levels correlated independently with lesion size in ApoE-/- mice. alpha-def-1 has competing effects on ath...
Title: Opposing effects of HNP1 (α-defensin-1) on plasma cholesterol and atherogenesis.
lower DEFA1/DEFA3 copy number (CNV < 7) is associated with higher susceptibility to hospital-acquired infections (HAIs) in critically ill patients, indicating that host genetic factors are involved in the development of HAIs
Title: Low-Copy Number Polymorphism in DEFA1/DEFA3 Is Associated with Susceptibility to Hospital-Acquired Infections in Critically Ill Patients.
Human Neutrophil Peptide 1 directly binds and neutralizes Exotoxin A of Pseudomonas aeruginosa.
Title: Neutralization of Pseudomonas auruginosa Exotoxin A by human neutrophil peptide 1.
Pretreatment of component b with human alpha-defensin-1 prior to addition of component a of Clostridium perfringens iota toxin prevented intoxication implicating that alpha-defensin-1 interacts with the toxin b component to prevent the formation of biologically active iota toxin on cells.
Title: Human alpha-defensin-1 protects cells from intoxication with Clostridium perfringens iota toxin.
DEFA1, DEFA3, and PPBP expression was significantly increased in hyperlipidemia and coronary heart disease patients compared with controls.
Title: PPBP and DEFA1/DEFA3 genes in hyperlipidaemia as feasible synergistic inflammatory biomarkers for coronary heart disease.
HNP1 upregulation of cytokine expression in pDCs was inhibited by blockade of NF-kappaB activation or knockdown of IRF1, demonstrating the importance of these two signaling events in HNP1-induced pDC activation.
Title: Alarmin human α defensin HNP1 activates plasmacytoid dendritic cells by triggering NF-κB and IRF1 signaling pathways.

Submit: New GeneRIF Correction See all GeneRIFs (92)

Phenotypes

Go to the top of the page Help

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
Genome-wide association study of chronic periodontitis in a general German population. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

Go to the top of the page Help

See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

Go to the top of the page Help

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Human alpha-defensin (HNP-1) slows down the HIV-1 Env (gp120/gp41) binding to CXCR4 but not CD4 or CCR5 on the kinetics of HIV-1 entry	PubMed
	env	Dimerization of HNP-1 is important for HNP-1 to bind HIV-1 gp120. W26A mutation abolishes the interaction between HNP-1 and gp120	PubMed
	env	Human neutrophil alpha-defensin 4 (HNP4) is more effective than HNP1-3 in protecting human peripheral blood mononuclear cells from infection by both CXCR4- and CCR5-tropic HIV-1 strains, but HNP4 binds to both CD4 and gp120 weaker than does HNP1	PubMed
	env	Alpha-defensins inhibit the binding of HIV-1 gp120 to CD4 through interaction with the D1 domain of CD4	PubMed
Envelope transmembrane glycoprotein gp41	env	Human alpha-defensin (HNP-1) augments the activity of inhibitory peptides and antibodies targeting the HIV-1 gp41 coiled-coil, C-HR, and MPER domains	PubMed
	env	Human alpha-defensin (HNP-1) slows down the HIV-1 Env (gp120/gp41) binding to CXCR4 but not CD4 or CCR5 on the kinetics of HIV-1 entry	PubMed
	env	HNP-1 inhibits trimerization of the HIV-1 gp41 N-terminal coiled coil domain and binds to both the C-terminal domain and the 6-helix bundle structure	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

Go to the top of the page Help

Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

Go to the top of the page Help

Markers

NoName (e-PCR)
- UniSTS:486943

RH71432 (e-PCR)
- UniSTS:66423

PMC152639P3 (e-PCR)
- UniSTS:271236

STS-N54165 (e-PCR)
- UniSTS:51153

NoName (e-PCR)
- UniSTS:481504

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables pore-forming activity	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in T cell chemotaxis	IDA Inferred from Direct Assay more info	PubMed
involved_in antibacterial humoral response	IBA Inferred from Biological aspect of Ancestor more info
involved_in antibacterial humoral response	IDA Inferred from Direct Assay more info	PubMed
involved_in antimicrobial humoral immune response mediated by antimicrobial peptide	IBA Inferred from Biological aspect of Ancestor more info
involved_in antimicrobial humoral immune response mediated by antimicrobial peptide	IC Inferred by Curator more info	PubMed
involved_in antimicrobial humoral immune response mediated by antimicrobial peptide	IDA Inferred from Direct Assay more info	PubMed
involved_in antimicrobial humoral immune response mediated by antimicrobial peptide	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cellular response to lipopolysaccharide	IBA Inferred from Biological aspect of Ancestor more info
involved_in chemotaxis	TAS Traceable Author Statement more info	PubMed
involved_in defense response to Gram-negative bacterium	IBA Inferred from Biological aspect of Ancestor more info
involved_in defense response to Gram-positive bacterium	IBA Inferred from Biological aspect of Ancestor more info
involved_in defense response to Gram-positive bacterium	IDA Inferred from Direct Assay more info	PubMed
involved_in defense response to fungus	IEA Inferred from Electronic Annotation more info
involved_in defense response to protozoan	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in defense response to virus	IEA Inferred from Electronic Annotation more info
involved_in disruption of plasma membrane integrity in another organism	IBA Inferred from Biological aspect of Ancestor more info
involved_in estrogen receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in immune response	TAS Traceable Author Statement more info	PubMed
involved_in innate immune response in mucosa	IBA Inferred from Biological aspect of Ancestor more info
involved_in innate immune response in mucosa	IDA Inferred from Direct Assay more info	PubMed
involved_in killing by host of symbiont cells	IDA Inferred from Direct Assay more info	PubMed
involved_in killing of cells of another organism	IDA Inferred from Direct Assay more info	PubMed

Component	Evidence Code	Pubs
located_in Golgi lumen	TAS Traceable Author Statement more info
located_in azurophil granule lumen	TAS Traceable Author Statement more info
colocalizes_with collagen-containing extracellular matrix	HDA more info	PubMed
located_in collagen-containing extracellular matrix	HDA more info	PubMed
located_in extracellular exosome	HDA more info	PubMed
located_in extracellular region	TAS Traceable Author Statement more info
located_in extracellular space	HDA more info	PubMed
is_active_in extracellular space	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular space	IDA Inferred from Direct Assay more info	PubMed

General protein information

Go to the top of the page Help

Preferred Names: neutrophil defensin 1

Names: defensin, alpha 1, myeloid-related sequence; defensin, alpha 2; myeloid-related sequence

NCBI Reference Sequences (RefSeq)

Go to the top of the page Help

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.