P59665 (DEF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Neutrophil defensin 1

Alternative name(s):
Defensin, alpha 1
HNP-1
Short name=HP-1
Short name=HP1

Cleaved into the following 2 chains:

1. HP 1-56
2. Neutrophil defensin 2
   Alternative name(s):
   HNP-2
   Short name=HP-2
   Short name=HP2

Gene names

Name:	DEFA1
Synonyms:	DEF1, DEFA2, MRS
AND
Name:	DEFA1B

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › 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.14 Ref.18
Subunit structure	Dimer. Ref.18
Subcellular location	Secreted.
Post-translational modification	ADP-ribosylation drastically reduces cytotoxic and antibacterial activities, and enhances IL8 production. Phosphorylation at Tyr-85 has been found in some cancer cell lines, and interferes with ADP-rybosylation.
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	ADP-ribosylation Disulfide bond Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	chemotaxis Traceable author statement PubMed 10914484. Source: ProtInc defense response to bacterium Inferred from electronic annotation. Source: UniProtKB-KW defense response to fungus Inferred from electronic annotation. Source: UniProtKB-KW defense response to virus Inferred from electronic annotation. Source: UniProtKB-KW innate immune response Traceable author statement. Source: Reactome killing of cells of other organism Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	Golgi lumen Traceable author statement. Source: Reactome azurophil granule lumen Traceable author statement. Source: Reactome extracellular region Traceable author statement. Source: Reactome 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.10

Propeptide

20 – 38

19

PRO_0000006771

Chain

39 – 94

56

HP 1-56

PRO_0000006772

Peptide

65 – 94

30

Neutrophil defensin 1 Ref.9

PRO_0000006773

Peptide

66 – 94

29

Neutrophil defensin 2

PRO_0000006774

Amino acid modifications

Modified residue

78

1

ADP-ribosylarginine; by ART1

Modified residue

85

1

Phosphotyrosine Ref.15

Modified residue

88

1

ADP-ribosylarginine; by ART1

Disulfide bond

66 ↔ 94

Ref.11

Disulfide bond

68 ↔ 83

Ref.11

Disulfide bond

73 ↔ 93

Ref.11

Secondary structure

1

.

.

.

.

.

.

.

94

Helix Strand Turn

Details...

Beta strand

66 – 72

7

Beta strand

79 – 85

7

Beta strand

88 – 93

6

Sequences

	Sequence		Length	Mass (Da)
	P59665 [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	Erratum Linzmeier R., Michaelson D., Liu L., Ganz T. FEBS Lett. 326:299-300(1993) [PubMed] [Europe PMC] [Abstract]
[7]	"DNA sequence and analysis of human chromosome 8." Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T. , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S. Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Liver.
[9]	"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] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 65-94.
[10]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 20-34.
[11]	"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] [Europe PMC] [Abstract] Cited for: DISULFIDE BONDS.
[12]	"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] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING.
[13]	"Posttranslational processing of defensins in immature human myeloid cells." Valore E.V., Ganz T. Blood 79:1538-1544(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEOLYTIC PROCESSING.
[14]	"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] [Europe PMC] [Abstract] Cited for: FUNCTION.
[15]	"Structural and functional consequences induced by post-translational modifications in alpha-Defensins." Balducci E., Bonucci A., Picchianti M., Pogni R., Talluri E. Int. J. Pept. 2011:594723-594723(2011) [PubMed] [Europe PMC] [Abstract] Cited for: ADP-RIBOSYLATION AT ARG-78 AND ARG-88 BY ART1, PHOSPHORYLATION AT TYR-85.
[16]	"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] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF DEFENSIN 1.
[17]	"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] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF DEFENSIN 1.
[18]	"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] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 65-94, FUNCTION, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M21130 mRNA. Translation: AAA52302.1.
M26602 mRNA. Translation: AAA52303.1.
L12690 Genomic DNA. Translation: AAA36382.1.
X52053 mRNA. Translation: CAA36280.1.
AF200455 Genomic DNA. Translation: AAT68875.1.
AF200455 Genomic DNA. Translation: AAT68878.1.
AF200455 Genomic DNA. Translation: AAT68879.1.
AF200455 Genomic DNA. Translation: AAT68880.1.
AF238378 Genomic DNA. Translation: AAT68883.1.
AF238378 Genomic DNA. Translation: AAT68884.1.
BC069423 mRNA. Translation: AAH69423.1.
BC093791 mRNA. Translation: AAH93791.1.
BC112188 mRNA. Translation: AAI12189.1.

IPI

IPI00005721.

PIR

A40499. S32499.

RefSeq

NP_001035965.1. NM_001042500.1.
NP_004075.1. NM_004084.3.

UniGene

Hs.380781.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KHT	NMR	-	A	65-94	[»]
2PM1	X-ray	1.60	A	65-94	[»]
3GNY	X-ray	1.56	A/B	65-94	[»]
3H6C	X-ray	1.63	A/B	65-94	[»]
3HJ2	X-ray	1.40	A/B	65-94	[»]
3HJD	X-ray	1.65	A/B	65-94	[»]
3LO1	X-ray	1.60	A	65-94	[»]
3LO2	X-ray	1.56	A/B	65-94	[»]
3LO4	X-ray	1.75	A/B	65-94	[»]
3LO6	X-ray	1.56	A/B	65-94	[»]
3LO9	X-ray	1.56	A/B	65-94	[»]
3LOE	X-ray	1.56	A	65-94	[»]
3LVX	X-ray	1.63	A/B	65-94	[»]
4DU0	X-ray	1.90	A/B/C/D	65-94	[»]

ProteinModelPortal

P59665.

ModBase

Search...

Protein-protein interaction databases

IntAct

P59665. 4 interactions.

STRING

9606.ENSP00000372126.

Protein family/group databases

TCDB

1.C.19.1.1. defensin family.

PTM databases

PhosphoSite

P59665.

Proteomic databases

PaxDb

P59665.

PeptideAtlas

P59665.

PRIDE

P59665.

Protocols and materials databases

DNASU

1667.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000382679; ENSP00000372126; ENSG00000206047.
ENST00000382689; ENSP00000372136; ENSG00000240247.
ENST00000382692; ENSP00000372139; ENSG00000206047.
ENST00000535841; ENSP00000443526; ENSG00000240247.

GeneID

1667.
728358.

KEGG

hsa:1667.
hsa:728358.

UCSC

uc003wqv.1. human.

Organism-specific databases

CTD

1667.
728358.

GeneCards

GC08M006822.
GC08M006843.

HGNC

HGNC:2761. DEFA1.
HGNC:33596. DEFA1B.

HPA

CAB032548.
HPA052517.

MIM

125220. gene.

neXtProt

NX_P59665.

PharmGKB

PA165585475.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG86943.

HOGENOM

HOG000233351.

HOVERGEN

HBG011703.

InParanoid

P59665.

KO

K05230.

OMA

RVWAFCC.

OrthoDB

EOG4GF3GT.

Enzyme and pathway databases

Pathway_Interaction_DB

anthraxpathway. Cellular roles of Anthrax toxin.

Reactome

REACT_6900. Immune System.

Gene expression databases

Bgee

P59665.

CleanEx

HS_DEFA1.

Genevestigator

P59665.

GermOnline

ENSG00000206047. Homo sapiens.

Family and domain databases

InterPro

IPR016327. Alpha-defensin.
IPR006080. Defensin_beta/neutrophil.
IPR002366. Defensin_propep.
IPR006081. Mammalian_defensins.
[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

ChiTaRS

DEFA1. human.

EvolutionaryTrace

P59665.

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, Q6EZF6

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 30, 2003
Last sequence update:	April 30, 2003
Last modified:	May 1, 2013
This is version 110 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.