Reviewed, UniProtKB/Swiss-Prot P59665 (DEF1_HUMAN)

Names and origin

Protein names

Recommended name:
    Neutrophil defensin 1
Alternative name(s):
    HNP-1
      Short name=HP-1
      Short name=HP1
    Defensin, alpha 1
Cleaved into the following 2 chains:
    1- Recommended name:
            HP 1-56
    2- Recommended name:
            Neutrophil defensin 2
        Alternative name(s):
            HNP-2
              Short name=HP-2
              Short name=HP2

Gene names

Name:	DEFA1
Synonyms:	DEF1, DEFA2, MRS

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	94 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	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. Ref.13 Ref.17
Subunit structure	Dimer. Ref.17
Subcellular location	Secreted.
Sequence similarities	Belongs to the alpha-defensin family.

Ontologies

Keywords
Biological process	Antiviral defense
Cellular component	Secreted
Domain	Signal
Molecular function	Antibiotic Antimicrobial Defensin Fungicide
PTM	Disulfide bond Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	chemotaxis Traceable author statement. Source: ProtInc defense response to bacterium Inferred from electronic annotation. Source: UniProtKB-KW defense response to fungus Inferred from electronic annotation. Source: UniProtKB-KW immune response Traceable author statement. Source: ProtInc response to virus Inferred from electronic annotation. Source: UniProtKB-KW xenobiotic metabolic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	extracellular space Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 19

19

Ref.9

Propeptide

20 – 38

19

PRO_0000006771

Chain

39 – 94

56

HP 1-56

PRO_0000006772

Peptide

65 – 94

30

Neutrophil defensin 1

PRO_0000006773

Peptide

66 – 94

29

Neutrophil defensin 2

PRO_0000006774

Amino acid modifications

Modified residue

85

1

Phosphotyrosine Ref.14

Disulfide bond

66 ↔ 94

Ref.10

Disulfide bond

68 ↔ 83

Ref.10

Disulfide bond

73 ↔ 93

Ref.10

Secondary structure

1

.

.

.

.

.

94

Helix Strand Turn

Details...

Beta strand

67 – 71

5

Beta strand

78 – 85

8

Sequences

	Sequence		Length	Mass (Da)
	P59665-1 [UniParc]. Last modified April 30, 2003. Version 1. Checksum: 0E0F8E95737396FA	FASTA	94	10,201
	10 20 30 40 50 60 MRTLAILAAI LLVALQAQAE PLQARADEVA AAPEQIAADI PEVVVSLAWD ESLAPKHPGS 70 80 90 RKNMACYCRI PACIAGERRY GTCIYQGRLW AFCC

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation and characterization of human defensin cDNA clones." Daher K.A., Lehrer R.I., Ganz T., Kronenberg M. Proc. Natl. Acad. Sci. U.S.A. 85:7327-7331(1988) [PubMed: 3174637] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"A myeloid-related sequence that localizes to human chromosome 8q21.1-22." Mars W.M., vanTuinen P., Drabkin H.A., White J.W., Saunders G.F. Blood 71:1713-1719(1988) [PubMed: 3370315] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Differentiation stage-specific expression of a gene during granulopoiesis." Wiedemann L.M., Francis G.E., Lamb R.F., Burns J.H., Winnie J.N., McKenzie E.D., Birnie G.D. Leukemia 3:227-234(1989) [PubMed: 2918759] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Inheritance of unequal numbers of the genes encoding the human neutrophil defensins HP-1 and HP-3." Mars W.M., Patmasiriwat P., Maity T., Huff V., Weil M.M., Saunders G.F. J. Biol. Chem. 270:30371-30376(1995) [PubMed: 8530462] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"The structure of neutrophil defensin genes." Linzmeier R., Michaelson D., Liu L., Ganz T. FEBS Lett. 321:267-273(1993) [PubMed: 8477861] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	Erratum Linzmeier R., Michaelson D., Liu L., Ganz T. FEBS Lett. 326:299-300(1993) [PubMed: 8325384] [Abstract]
[7]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[8]	"Primary structures of three human neutrophil defensins." Selsted M.E., Harwig S.S.L., Ganz T., Schilling J.W., Lehrer R.I. J. Clin. Invest. 76:1436-1439(1985) [PubMed: 4056036] [Abstract] Cited for: PROTEIN SEQUENCE OF 65-94.
[9]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed: 15340161] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-34.
[10]	"Determination of the disulfide array in the human defensin HNP-2. A covalently cyclized peptide." Selsted M.E., Harwig S.S.L. J. Biol. Chem. 264:4003-4007(1989) [PubMed: 2917986] [Abstract] Cited for: DISULFIDE BONDS.
[11]	"The isolation and identification of multiple forms of the neutrophil granule peptides from human leukemic cells." Bateman A., Singh A., Shustik C., Mars W.M., Solomon S. J. Biol. Chem. 266:7524-7530(1991) [PubMed: 2019582] [Abstract] Cited for: PROTEOLYTIC PROCESSING.
[12]	"Posttranslational processing of defensins in immature human myeloid cells." Valore E.V., Ganz T. Blood 79:1538-1544(1992) [PubMed: 1339298] [Abstract] Cited for: PROTEOLYTIC PROCESSING.
[13]	"Antibacterial activity and specificity of the six human alpha-defensins." Ericksen B., Wu Z., Lu W., Lehrer R.I. Antimicrob. Agents Chemother. 49:269-275(2005) [PubMed: 15616305] [Abstract] Cited for: FUNCTION.
[14]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-85, MASS SPECTROMETRY. Tissue: Lung.
[15]	"NMR studies of defensin antimicrobial peptides. 1. Resonance assignment and secondary structure determination of rabbit NP-2 and human HNP-1." Zhang X.-L., Selsted M.E., Pardi A. Biochemistry 31:11348-11356(1992) [PubMed: 1445872] [Abstract] Cited for: STRUCTURE BY NMR OF DEFENSIN 1.
[16]	"NMR studies of defensin antimicrobial peptides. 2. Three-dimensional structures of rabbit NP-2 and human HNP-1." Pardi A., Zhang X.-L., Selsted M.E., Skalicky J.J., Yip P.F. Biochemistry 31:11357-11364(1992) [PubMed: 1445873] [Abstract] Cited for: STRUCTURE BY NMR OF DEFENSIN 1.
[17]	"Toward understanding the cationicity of defensins. Arg and Lys versus their noncoded analogs." Zou G., de Leeuw E., Li C., Pazgier M., Li C., Zeng P., Lu W.-Y., Lubkowski J., Lu W. J. Biol. Chem. 282:19653-19665(2007) [PubMed: 17452329] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 65-94, FUNCTION, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

M21130 mRNA. Translation: AAA52302.1.
M26602 mRNA. Translation: AAA52303.1.
L12690 Genomic DNA. Translation: AAA36382.1.
X52053 mRNA. Translation: CAA36280.1.
BC069423 mRNA. Translation: AAH69423.1.

IPI

IPI00005721.

PIR

A40499. S32499.

RefSeq

NP_001035965.1.
NP_004075.1.

UniGene

Hs.380781

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2PM1	X-ray	1.60	A	65-94	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P59665. 1 interaction.

Protein family/group databases

TCDB

1.C.19.1.1. defensin family.

PTM databases

PhosphoSite

P59665.

Proteomic databases

PeptideAtlas

P59665.

PRIDE

P59665.

Genome annotation databases

Ensembl

ENSG00000206047. Homo sapiens. [Contig view]
ENSG00000215377. Homo sapiens. [Contig view]

GeneID

1667.
728358.

KEGG

hsa:1667.
hsa:728358.

Organism-specific databases

GeneCards

GC08M006822.
GC08M006842.

H-InvDB

HIX0034280.
HIX0034351.

HGNC

HGNC:2761. DEFA1.

MIM

125220. gene.

PharmGKB

PA27238.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P59665.

HOVERGEN

P59665.

OMA

P59665. MACYCRI.

Enzyme and pathway databases

Pathway_Interaction_DB

anthraxpathway. Cellular roles of Anthrax toxin.

Gene expression databases

Bgee

P59665.

CleanEx

HS_DEFA1.

GermOnline

ENSG00000206047. Homo sapiens.

Family and domain databases

InterPro

IPR016327. Alpha-defensin.
IPR006081. Defensin_alpha.
IPR006080. Defensin_mammal.
IPR002366. Defensin_propep.
[Graphical view]

Pfam

PF00323. Defensin_1. 1 hit.
PF00879. Defensin_propep. 1 hit.
[Graphical view]

PIRSF

PIRSF001875. Alpha-defensin. 1 hit.

SMART

SM00048. DEFSN. 1 hit.
[Graphical view]

PROSITE

PS00269. DEFENSIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

6860.

PMAP-CutDB

P59665.

SOURCE

Search...

Entry information

Entry name

DEF1_HUMAN

Accession

Primary (citable) accession number: P59665
Secondary accession number(s): P11479, Q14125

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 30, 2003
Last sequence update:	April 30, 2003
Last modified:	June 16, 2009
This is version 69 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)