Reviewed, UniProtKB/Swiss-Prot P12838 (DEF4_HUMAN)

Names and origin

Protein names

Recommended name:
    Neutrophil defensin 4
Alternative name(s):
    HNP-4
      Short name=HP-4
    Defensin, alpha 4

Gene names

Name:	DEFA4
Synonyms:	DEF4

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

Protein attributes

Sequence length	97 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	Has antimicrobial activity against Gram-negative bacteria, and to a lesser extent also against Gram-positive bacteria and fungi. Protects blood cells against infection with HIV-1 (in vitro). Inhibits corticotropin (ACTH)-stimulated corticosterone production. Ref.5 Ref.6
Subunit structure	Homodimer. Ref.7
Subcellular location	Secreted.
Sequence similarities	Belongs to the alpha-defensin family.

Ontologies

Keywords
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Antibiotic Antimicrobial Defensin Fungicide
PTM	Disulfide bond
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	defense response to bacterium Inferred from electronic annotation. Source: UniProtKB-KW defense response to fungus Inferred from electronic annotation. Source: UniProtKB-KW killing of cells of another organism 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

Potential

Propeptide

20 – 63

44

PRO_0000006781

Peptide

64 – 96

33

Neutrophil defensin 4 Ref.2 Ref.3

PRO_0000006782

Propeptide

97

1

PRO_0000006783

Amino acid modifications

Disulfide bond

65 ↔ 93

Ref.7

Disulfide bond

67 ↔ 82

Ref.7

Disulfide bond

72 ↔ 92

Ref.7

Natural variations

Natural variant

8

1

A → P: dbSNP rs28661751.

VAR_048861

Natural variant

74

1

R → Q in a colorectal cancer sample; somatic mutation. Ref.8

VAR_036315

Secondary structure

1

.

.

.

.

.

.

.

97

Helix Strand Turn

Details...

Beta strand

65 – 70

6

Beta strand

77 – 84

8

Beta strand

87 – 93

7

Sequences

	Sequence		Length	Mass (Da)
	P12838-1 [UniParc]. Last modified July 1, 1993. Version 2. Checksum: FE14334631EC2FD3	FASTA	97	10,504
	10 20 30 40 50 60 MRIIALLAAI LLVALQVRAG PLQARGDEAP GQEQRGPEDQ DISISFAWDK SSALQVSGST 70 80 90 RGMVCSCRLV FCRRTELRVG NCLIGGVSFT YCCTRVD

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The gene encoding the human corticostatin HP-4 precursor contains a recent 86-base duplication and is located on chromosome 8." Palfree R.G.E., Sadro L.C., Solomon S. Mol. Endocrinol. 7:199-205(1993) [PubMed: 8469233] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Bone marrow.
[2]	"Structure of a novel human granulocyte peptide with anti-ACTH activity." Singh A., Bateman A., Zhu Q., Shimasaki S., Esch F., Solomon S. Biochem. Biophys. Res. Commun. 155:524-529(1988) [PubMed: 2843187] [Abstract] Cited for: PROTEIN SEQUENCE OF 64-96.
[3]	"Purification and characterization of human neutrophil peptide 4, a novel member of the defensin family." Wilde C.G., Griffith J.E., Marra M.N., Snable J.L., Scott R.W. J. Biol. Chem. 264:11200-11203(1989) [PubMed: 2500436] [Abstract] Cited for: PROTEIN SEQUENCE OF 64-96.
[4]	"Antibiotic proteins of human polymorphonuclear leukocytes." Gabay J.E., Scott R.W., Campanelli D., Griffith J., Wilde C., Marra M.N., Seeger M., Nathan C.F. Proc. Natl. Acad. Sci. U.S.A. 86:5610-5614(1989) [PubMed: 2501794] [Abstract] Cited for: PROTEIN SEQUENCE OF 64-83.
[5]	"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.
[6]	"Human neutrophil alpha-defensin 4 inhibits HIV-1 infection in vitro." Wu Z., Cocchi F., Gentles D., Ericksen B., Lubkowski J., Devico A., Lehrer R.I., Lu W. FEBS Lett. 579:162-166(2005) [PubMed: 15620707] [Abstract] Cited for: FUNCTION.
[7]	"Crystal structures of human alpha-defensins HNP4, HD5, and HD6." Szyk A., Wu Z., Tucker K., Yang D., Lu W., Lubkowski J. Protein Sci. 15:2749-2760(2006) [PubMed: 17088326] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 64-96, SUBUNIT, DISULFIDE BONDS.
[8]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLN-74.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

U18745 Genomic DNA. Translation: AAA64488.1.
X65977 mRNA. Translation: CAA46792.1.

IPI

IPI00025866.

PIR

A47365.

RefSeq

NP_001916.1.

UniGene

Hs.591391

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ZMM	X-ray	1.60	A/B/C/D	64-96	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

P12838.

Proteomic databases

PRIDE

P12838.

Genome annotation databases

Ensembl

ENST00000297435; ENSP00000297435; ENSG00000164821; Homo sapiens. [Genome view]

GeneID

1669.

KEGG

hsa:1669.

UCSC

uc003wqu.1. human.

Organism-specific databases

CTD

1669.

GeneCards

GC08M006780.

H-InvDB

HIX0034376.

HGNC

HGNC:2763. DEFA4.

MIM

601157. gene.

PharmGKB

PA27240.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P12838.

HOVERGEN

P12838.

OMA

DKSSALQ.

Gene expression databases

ArrayExpress

P12838.

Bgee

P12838.

CleanEx

HS_DEFA4.

Genevestigator

P12838.

GermOnline

ENSG00000164821. 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

6868.

SOURCE

Search...

Entry information

Entry name

DEF4_HUMAN

Accession

Primary (citable) accession number: P12838

Entry history

Integrated into UniProtKB/Swiss-Prot:	October 1, 1989
Last sequence update:	July 1, 1993
Last modified:	November 3, 2009
This is version 85 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.