Defensin, alpha 1

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Defensin, alpha 1
Protein DEFA1 PDB 1dfn.png
PDB rendering based on 1dfn.
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols DEFA1 ; DEF1; DEFA2; HNP-1; HP-1; HP1; MRS
External IDs OMIM125220 HomoloGene128756 GeneCards: DEFA1 Gene
RNA expression pattern
PBB GE DEFA1 205033 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1667 n/a
Ensembl ENSG00000206047 n/a
UniProt P59665 n/a
RefSeq (mRNA) NM_004084 n/a
RefSeq (protein) NP_004075 n/a
Location (UCSC) Chr 8:
6.84 – 6.84 Mb
n/a
PubMed search [1] n/a

Defensin, alpha 1 also known as human alpha defensin 1, human neutrophil peptide 1 (HNP-1) or neutrophil defensin 1 is a human protein that is encoded by the DEFA1 gene.[1][2][3] Human alpha defensin 1 belongs to the alpha defensin family of antimicrobial peptides.

Function[edit]

Defensins are a family of microbicidal 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. Several alpha defensin genes are clustered on chromosome 8. 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. It differs from the defensins, alpha 2 and alpha 3 by only one amino acid.[3]

Biosynthesis[edit]

HNPs are generated as 94 amino acids preproHNPs, which are co-translationally cleaved to 75 amino acids pro-peptides with a N-terminal prosegment having a negative charge that neutralizes the highly positively charged C terminal peptide. Processing of proHNPs occurs mainly in late promyelocytes, where the 75 amino acids proHNPs are cleaved to a 56 amino acids intermediate form and onward to 29-30 amino acids mature peptides designated HNPs.[4][5] Cationic 29-30 amino acids HNPs associate with the negatively charged proteoglycan serglycin and translocate to azurophil granules.[6] At later stages of granulocytic differentiation in which HNP expression peaks (i.e. myelocytes and metamyelocytes), proHNPs are not cleaved, rendering the peptides overall neutral. This prevents binding to serglycin and most proHNP is accordingly secreted into the bone marrow plasma although some is retained in specific granules.[7]

References[edit]

  1. ^ Feng Y, Gutekunst CA, Eberhart DE, Yi H, Warren ST, Hersch SM (Mar 1997). "Fragile X mental retardation protein: nucleocytoplasmic shuttling and association with somatodendritic ribosomes". J Neurosci 17 (5): 1539–47. PMID 9030614. 
  2. ^ Aldred PM, Hollox EJ, Armour JA (Jul 2005). "Copy number polymorphism and expression level variation of the human alpha-defensin genes DEFA1 and DEFA3". Hum Mol Genet 14 (14): 2045–52. doi:10.1093/hmg/ddi209. PMID 15944200. 
  3. ^ a b "Entrez Gene: DEFA1 defensin, alpha 1". 
  4. ^ Valore EV, Ganz T (Mar 15, 1992). "Posttranslational processing of defensins in immature human myeloid cells.". Blood 79 (6): 1538–44. PMID 1339298. 
  5. ^ Arnljots K, Sørensen O, Lollike K, Borregaard N (Nov 1998). "Timing, targeting and sorting of azurophil granule proteins in human myeloid cells.". Leukemia 12 (11): 1789–95. doi:10.1038/sj.leu.2401202. PMID 9823955. 
  6. ^ Glenthøj A, Cowland JB, Heegaard NH, Larsen MT, Borregaard N (Oct 20, 2011). "Serglycin participates in retention of α-defensin in granules during myelopoiesis.". Blood 118 (16): 4440–8. doi:10.1182/blood-2011-06-362947. PMID 21849484. 
  7. ^ Faurschou M, Kamp S, Cowland JB, Udby L, Johnsen AH, Calafat J, Winther H, Borregaard N (Sep 2005). "Prodefensins are matrix proteins of specific granules in human neutrophils.". Journal of leukocyte biology 78 (3): 785–93. doi:10.1189/jlb.1104688. PMID 15944211. 

Further reading[edit]