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P59665 (DEF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 122. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length94 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence 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-ribosylation.

Sequence similarities

Belongs to the alpha-defensin family.

Ontologies

Keywords
   Biological processAntiviral defense
   Cellular componentSecreted
   DomainSignal
   Molecular functionAntibiotic
Antimicrobial
Defensin
Fungicide
   PTMADP-ribosylation
Disulfide bond
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processantibacterial humoral response

Inferred from direct assay PubMed 12860195Ref.14. Source: UniProt

chemotaxis

Traceable author statement PubMed 10914484. Source: ProtInc

defense response to Gram-positive bacterium

Inferred from direct assay PubMed 12860195. Source: UniProt

defense response to fungus

Inferred from electronic annotation. Source: UniProtKB-KW

defense response to virus

Inferred from electronic annotation. Source: UniProtKB-KW

immune response

Traceable author statement PubMed 10914484. Source: ProtInc

innate immune response

Inferred from direct assay Ref.14. Source: UniProt

innate immune response in mucosa

Inferred from direct assay PubMed 12860195. Source: UniProt

intracellular estrogen receptor signaling pathway

Inferred from direct assay PubMed 21861873. Source: UniProt

killing of cells of other organism

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentGolgi 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 direct assay PubMed 12860195PubMed 16502470PubMed 21861873. Source: UniProt

extracellular vesicular exosome

Inferred from direct assay PubMed 19199708. Source: UniProt

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1919 Ref.10
Propeptide20 – 3819
PRO_0000006771
Chain39 – 9456HP 1-56
PRO_0000006772
Peptide65 – 9430Neutrophil defensin 1 Ref.9
PRO_0000006773
Peptide66 – 9429Neutrophil defensin 2
PRO_0000006774

Amino acid modifications

Modified residue781ADP-ribosylarginine; by ART1
Modified residue851Phosphotyrosine Ref.15
Modified residue881ADP-ribosylarginine; by ART1
Disulfide bond66 ↔ 94 Ref.11
Disulfide bond68 ↔ 83 Ref.11
Disulfide bond73 ↔ 93 Ref.11

Secondary structure

....... 94
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P59665 [UniParc].

Last modified April 30, 2003. Version 1.
Checksum: 0E0F8E95737396FA

FASTA9410,201
        10         20         30         40         50         60 
MRTLAILAAI LLVALQAQAE PLQARADEVA AAPEQIAADI PEVVVSLAWD ESLAPKHPGS 

        70         80         90 
RKNMACYCRI PACIAGERRY GTCIYQGRLW AFCC 

« Hide

References

« Hide '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. expand/collapse author list , 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.
CCDSCCDS34797.1.
CCDS43691.1.
PIRA40499. S32499.
RefSeqNP_001035965.1. NM_001042500.1.
NP_004075.1. NM_004084.3.
UniGeneHs.380781.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2KHTNMR-A65-94[»]
2PM1X-ray1.60A65-94[»]
3GNYX-ray1.56A/B65-94[»]
3H6CX-ray1.63A/B65-94[»]
3HJ2X-ray1.40A/B65-94[»]
3HJDX-ray1.65A/B65-94[»]
3LO1X-ray1.60A65-94[»]
3LO2X-ray1.56A/B65-94[»]
3LO4X-ray1.75A/B65-94[»]
3LO6X-ray1.56A/B65-94[»]
3LO9X-ray1.56A/B65-94[»]
3LOEX-ray1.56A65-94[»]
3LVXX-ray1.63A/B65-94[»]
4DU0X-ray1.90A/B/C/D65-94[»]
4LB1X-ray2.00A/B/D/E65-94[»]
4LB7X-ray1.90A/B/D/E65-94[»]
4LBBX-ray1.72A/B65-94[»]
4LBFX-ray1.70A/B/C/D/E/F/G/H65-94[»]
ProteinModelPortalP59665.
SMRP59665. Positions 65-94.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108031. 3 interactions.
IntActP59665. 5 interactions.
MINTMINT-6631351.
STRING9606.ENSP00000372126.

Protein family/group databases

TCDB1.C.19.1.1. the defensin (defensin) family.

PTM databases

PhosphoSiteP59665.

Polymorphism databases

DMDM30316322.

Proteomic databases

PaxDbP59665.
PeptideAtlasP59665.
PRIDEP59665.

Protocols and materials databases

DNASU1667.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000382679; ENSP00000372126; ENSG00000206047.
ENST00000382689; ENSP00000372136; ENSG00000240247.
ENST00000382692; ENSP00000372139; ENSG00000206047.
ENST00000535841; ENSP00000443526; ENSG00000240247.
GeneID1667.
728358.
KEGGhsa:1667.
hsa:728358.
UCSCuc003wqv.1. human.

Organism-specific databases

CTD1667.
728358.
GeneCardsGC08M006822.
GC08M006843.
HGNCHGNC:2761. DEFA1.
HGNC:33596. DEFA1B.
HPACAB032548.
HPA052517.
MIM125220. gene.
neXtProtNX_P59665.
PharmGKBPA165585475.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG86943.
HOGENOMHOG000233351.
HOVERGENHBG011703.
InParanoidP59665.
KOK05230.
OMARVWAFCC.
OrthoDBEOG75TMFQ.
PhylomeDBP59665.
TreeFamTF338414.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Gene expression databases

BgeeP59665.
CleanExHS_DEFA1.
GenevestigatorP59665.

Family and domain databases

InterProIPR016327. Alpha-defensin.
IPR006080. Defensin_beta/neutrophil.
IPR002366. Defensin_propep.
IPR006081. Mammalian_defensins.
[Graphical view]
PANTHERPTHR11876. PTHR11876. 1 hit.
PfamPF00323. Defensin_1. 1 hit.
PF00879. Defensin_propep. 1 hit.
[Graphical view]
PIRSFPIRSF001875. Alpha-defensin. 1 hit.
SMARTSM00048. DEFSN. 1 hit.
[Graphical view]
PROSITEPS00269. DEFENSIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSDEFA1. human.
EvolutionaryTraceP59665.
GeneWikiDEFA1B.
Defensin,_alpha_1.
NextBio6860.
PMAP-CutDBP59665.
PROP59665.
SOURCESearch...

Entry information

Entry nameDEF1_HUMAN
AccessionPrimary (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: July 9, 2014
This is version 122 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM