ID   DEF4_HUMAN              Reviewed;          97 AA.
AC   P12838;
DT   01-OCT-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-JUL-1993, sequence version 2.
DT   25-JAN-2012, entry version 101.
DE   RecName: Full=Neutrophil defensin 4;
DE   AltName: Full=Defensin, alpha 4;
DE   AltName: Full=HNP-4;
DE            Short=HP-4;
DE   Flags: Precursor;
GN   Name=DEFA4; Synonyms=DEF4;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Bone marrow;
RX   MEDLINE=93225961; PubMed=8469233; DOI=10.1210/me.7.2.199;
RA   Palfree R.G.E., Sadro L.C., Solomon S.;
RT   "The gene encoding the human corticostatin HP-4 precursor contains a
RT   recent 86-base duplication and is located on chromosome 8.";
RL   Mol. Endocrinol. 7:199-205(1993).
RN   [2]
RP   PROTEIN SEQUENCE OF 64-96.
RX   MEDLINE=88326354; PubMed=2843187; DOI=10.1016/S0006-291X(88)81118-5;
RA   Singh A., Bateman A., Zhu Q., Shimasaki S., Esch F., Solomon S.;
RT   "Structure of a novel human granulocyte peptide with anti-ACTH
RT   activity.";
RL   Biochem. Biophys. Res. Commun. 155:524-529(1988).
RN   [3]
RP   PROTEIN SEQUENCE OF 64-96.
RX   MEDLINE=89291867; PubMed=2500436;
RA   Wilde C.G., Griffith J.E., Marra M.N., Snable J.L., Scott R.W.;
RT   "Purification and characterization of human neutrophil peptide 4, a
RT   novel member of the defensin family.";
RL   J. Biol. Chem. 264:11200-11203(1989).
RN   [4]
RP   PROTEIN SEQUENCE OF 64-83.
RX   MEDLINE=89315847; PubMed=2501794; DOI=10.1073/pnas.86.14.5610;
RA   Gabay J.E., Scott R.W., Campanelli D., Griffith J., Wilde C.,
RA   Marra M.N., Seeger M., Nathan C.F.;
RT   "Antibiotic proteins of human polymorphonuclear leukocytes.";
RL   Proc. Natl. Acad. Sci. U.S.A. 86:5610-5614(1989).
RN   [5]
RP   FUNCTION.
RX   PubMed=15616305; DOI=10.1128/AAC.49.1.269-275.2005;
RA   Ericksen B., Wu Z., Lu W., Lehrer R.I.;
RT   "Antibacterial activity and specificity of the six human alpha-
RT   defensins.";
RL   Antimicrob. Agents Chemother. 49:269-275(2005).
RN   [6]
RP   FUNCTION.
RX   PubMed=15620707; DOI=10.1016/j.febslet.2004.11.062;
RA   Wu Z., Cocchi F., Gentles D., Ericksen B., Lubkowski J., Devico A.,
RA   Lehrer R.I., Lu W.;
RT   "Human neutrophil alpha-defensin 4 inhibits HIV-1 infection in
RT   vitro.";
RL   FEBS Lett. 579:162-166(2005).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 64-96, SUBUNIT, AND DISULFIDE
RP   BONDS.
RX   PubMed=17088326; DOI=10.1110/ps.062336606;
RA   Szyk A., Wu Z., Tucker K., Yang D., Lu W., Lubkowski J.;
RT   "Crystal structures of human alpha-defensins HNP4, HD5, and HD6.";
RL   Protein Sci. 15:2749-2760(2006).
RN   [8]
RP   VARIANT [LARGE SCALE ANALYSIS] GLN-74.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA   Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA   Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA   Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA   Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal
RT   cancers.";
RL   Science 314:268-274(2006).
CC   -!- FUNCTION: Has antimicrobial activity against Gram-negative
CC       bacteria, and to a lesser extent also against Gram-positive
CC       bacteria and fungi. Protects blood cells against infection with
CC       HIV-1 (in vitro). Inhibits corticotropin (ACTH)-stimulated
CC       corticosterone production.
CC   -!- SUBUNIT: Homodimer.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- SIMILARITY: Belongs to the alpha-defensin family.
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DR   EMBL; U18745; AAA64488.1; -; Genomic_DNA.
DR   EMBL; X65977; CAA46792.1; -; mRNA.
DR   IPI; IPI00025866; -.
DR   PIR; A47365; A47365.
DR   RefSeq; NP_001916.1; NM_001925.1.
DR   UniGene; Hs.591391; -.
DR   PDB; 1ZMM; X-ray; 1.60 A; A/B/C/D=64-96.
DR   PDBsum; 1ZMM; -.
DR   ProteinModelPortal; P12838; -.
DR   SMR; P12838; 64-96.
DR   STRING; P12838; -.
DR   DMDM; 399352; -.
DR   PRIDE; P12838; -.
DR   Ensembl; ENST00000297435; ENSP00000297435; ENSG00000164821.
DR   GeneID; 1669; -.
DR   KEGG; hsa:1669; -.
DR   UCSC; uc003wqu.1; human.
DR   CTD; 1669; -.
DR   GeneCards; GC08M006780; -.
DR   H-InvDB; HIX0034376; -.
DR   HGNC; HGNC:2763; DEFA4.
DR   MIM; 601157; gene.
DR   neXtProt; NX_P12838; -.
DR   PharmGKB; PA27240; -.
DR   eggNOG; maNOG24475; -.
DR   HOGENOM; HBG283450; -.
DR   HOVERGEN; HBG011703; -.
DR   InParanoid; P12838; -.
DR   OMA; AWDKSSA; -.
DR   OrthoDB; EOG4GF3GT; -.
DR   PhylomeDB; P12838; -.
DR   NextBio; 6868; -.
DR   ArrayExpress; P12838; -.
DR   Bgee; P12838; -.
DR   CleanEx; HS_DEFA4; -.
DR   Genevestigator; P12838; -.
DR   GermOnline; ENSG00000164821; Homo sapiens.
DR   GO; GO:0005615; C:extracellular space; IEA:InterPro.
DR   GO; GO:0042742; P:defense response to bacterium; IEA:UniProtKB-KW.
DR   GO; GO:0050832; P:defense response to fungus; IEA:UniProtKB-KW.
DR   GO; GO:0031640; P:killing of cells of other organism; IEA:UniProtKB-KW.
DR   InterPro; IPR016327; Alpha-defensin.
DR   InterPro; IPR006080; Defensin_beta/neutrophil.
DR   InterPro; IPR002366; Defensin_propep.
DR   InterPro; IPR006081; Mammalian_defensins.
DR   KO; K05230; -.
DR   PANTHER; PTHR11876; PTHR11876; 1.
DR   Pfam; PF00323; Defensin_1; 1.
DR   Pfam; PF00879; Defensin_propep; 1.
DR   PIRSF; PIRSF001875; Alpha-defensin; 1.
DR   SMART; SM00048; DEFSN; 1.
DR   PROSITE; PS00269; DEFENSIN; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Antibiotic; Antimicrobial; Complete proteome; Defensin;
KW   Direct protein sequencing; Disulfide bond; Fungicide; Polymorphism;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL        1     19       Potential.
FT   PROPEP       20     63
FT                                /FTId=PRO_0000006781.
FT   PEPTIDE      64     96       Neutrophil defensin 4.
FT                                /FTId=PRO_0000006782.
FT   PROPEP       97     97
FT                                /FTId=PRO_0000006783.
FT   DISULFID     65     93
FT   DISULFID     67     82
FT   DISULFID     72     92
FT   VARIANT       8      8       A -> P (in dbSNP:rs28661751).
FT                                /FTId=VAR_048861.
FT   VARIANT       8      8       A -> V (in dbSNP:rs28488529).
FT                                /FTId=VAR_061132.
FT   VARIANT      74     74       R -> Q (in a colorectal cancer sample;
FT                                somatic mutation).
FT                                /FTId=VAR_036315.
FT   STRAND       65     70
FT   STRAND       77     84
FT   STRAND       87     93
SQ   SEQUENCE   97 AA;  10504 MW;  FE14334631EC2FD3 CRC64;
     MRIIALLAAI LLVALQVRAG PLQARGDEAP GQEQRGPEDQ DISISFAWDK SSALQVSGST
     RGMVCSCRLV FCRRTELRVG NCLIGGVSFT YCCTRVD
//