ID   DFB4A_HUMAN             Reviewed;          64 AA.
AC   O15263; Q52LC0;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   01-JAN-1998, sequence version 1.
DT   13-FEB-2019, entry version 173.
DE   RecName: Full=Beta-defensin 4A;
DE   AltName: Full=Beta-defensin 2;
DE            Short=BD-2;
DE            Short=hBD-2;
DE   AltName: Full=Defensin, beta 2;
DE   AltName: Full=Skin-antimicrobial peptide 1;
DE            Short=SAP1;
DE   Flags: Precursor;
GN   Name=DEFB4A; Synonyms=DEFB102, DEFB2, DEFB4;
GN   and
GN   Name=DEFB4B;
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=Skin;
RX   PubMed=9202117; DOI=10.1038/43088;
RA   Harder J., Bartels J.H., Christophers E., Schroeder J.-M.;
RT   "A peptide antibiotic from human skin.";
RL   Nature 387:861-861(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   TISSUE=Placenta;
RX   PubMed=9831658; DOI=10.1016/S0378-1119(98)00480-6;
RA   Liu L., Wang L., Jia H.P., Zhao C., Heng H.H.Q., Schutte B.C.,
RA   McCray P.B. Jr., Ganz T.;
RT   "Structure and mapping of the human beta-defensin HBD-2 gene and its
RT   expression at sites of inflammation.";
RL   Gene 222:237-244(1998).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=10603376; DOI=10.1128/IAI.68.1.113-119.2000;
RA   Diamond G., Kaiser V., Rhodes J., Russell J.P., Bevins C.L.;
RT   "Transcriptional regulation of beta-defensin gene expression in
RT   tracheal epithelial cells.";
RL   Infect. Immun. 68:113-119(2000).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=10837369; DOI=10.1165/ajrcmb.22.6.4023;
RA   Harder J., Meyer-Hoffert U., Teran L.M., Schwichtenberg L.,
RA   Bartels J., Maune S., Schroeder J.-M.;
RT   "Mucoid Pseudomonas aeruginosa, TNF-alpha, and IL-1beta, but not IL-6,
RT   induce human beta-defensin-2 in respiratory epithelia.";
RL   Am. J. Respir. Cell Mol. Biol. 22:714-721(2000).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Brain;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [6]
RP   SYNTHESIS OF 24-64.
RX   PubMed=12010514; DOI=10.1034/j.1399-3011.2002.00980.x;
RA   Kluever E., Schulz A., Forssmann W.-G., Adermann K.;
RT   "Chemical synthesis of beta-defensins and LEAP-1/hepcidin.";
RL   J. Pept. Res. 59:241-248(2002).
RN   [7]
RP   FUNCTION, AND BINDING TO CCR6.
RX   PubMed=20068036; DOI=10.1074/jbc.M109.091090;
RA   Roehrl J., Yang D., Oppenheim J.J., Hehlgans T.;
RT   "Specific binding and chemotactic activity of mBD4 and its functional
RT   orthologue hBD2 to CCR6-expressing cells.";
RL   J. Biol. Chem. 285:7028-7034(2010).
RN   [8]
RP   X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS).
RX   PubMed=10906336; DOI=10.1074/jbc.M006098200;
RA   Hoover D.M., Rajashankar K.R., Blumenthal R., Puri A., Oppenheim J.J.,
RA   Chertov O., Lubkowski J.;
RT   "The structure of human beta-defensin-2 shows evidence of higher order
RT   oligomerization.";
RL   J. Biol. Chem. 275:32911-32918(2000).
RN   [9]
RP   STRUCTURE BY NMR OF 28-64.
RX   PubMed=11714914; DOI=10.1110/ps.24401;
RA   Bauer F., Schweimer K., Kluever E., Conejo-Garcia J.-R.,
RA   Forssmann W.-G., Roesch P., Adermann K., Sticht H.;
RT   "Structure determination of human and murine beta-defensins reveals
RT   structural conservation in the absence of significant sequence
RT   similarity.";
RL   Protein Sci. 10:2470-2479(2001).
CC   -!- FUNCTION: Exhibits antimicrobial activity against Gram-negative
CC       bacteria and Gram-positive bacteria. May act as a ligand for C-C
CC       chemokine receptor CCR6. Can bind to both human and mouse CCR6 and
CC       induce chemotactic activity of CCR6-expressing cells
CC       (PubMed:20068036). {ECO:0000269|PubMed:20068036}.
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- TISSUE SPECIFICITY: Expressed in the skin and respiratory tract.
CC   -!- INDUCTION: By inflammation.
CC   -!- SIMILARITY: Belongs to the beta-defensin family. LAP/TAP
CC       subfamily. {ECO:0000305}.
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DR   EMBL; Z71389; CAA95992.1; -; mRNA.
DR   EMBL; AF040153; AAC33549.1; -; Genomic_DNA.
DR   EMBL; AF071216; AAC69554.1; -; Genomic_DNA.
DR   EMBL; AJ000152; CAB65126.1; -; Genomic_DNA.
DR   EMBL; BC069285; AAH69285.1; -; mRNA.
DR   EMBL; BC093983; AAH93983.1; -; mRNA.
DR   EMBL; BC093985; AAH93985.1; -; mRNA.
DR   CCDS; CCDS5971.1; -.
DR   RefSeq; NP_001192195.1; NM_001205266.1.
DR   RefSeq; NP_004933.1; NM_004942.3.
DR   UniGene; Hs.105924; -.
DR   UniGene; Hs.740237; -.
DR   PDB; 1E4Q; NMR; -; A=28-64.
DR   PDB; 1FD3; X-ray; 1.35 A; A/B/C/D=24-64.
DR   PDB; 1FD4; X-ray; 1.70 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=24-64.
DR   PDB; 1FQQ; NMR; -; A=24-64.
DR   PDB; 6CS9; X-ray; 1.85 A; A/B=24-64.
DR   PDBsum; 1E4Q; -.
DR   PDBsum; 1FD3; -.
DR   PDBsum; 1FD4; -.
DR   PDBsum; 1FQQ; -.
DR   PDBsum; 6CS9; -.
DR   ProteinModelPortal; O15263; -.
DR   SMR; O15263; -.
DR   BioGrid; 108037; 3.
DR   STRING; 9606.ENSP00000424598; -.
DR   BindingDB; O15263; -.
DR   TCDB; 1.C.85.1.2; the pore-forming -defensin (-defensin) family.
DR   BioMuta; DEFB4A; -.
DR   PaxDb; O15263; -.
DR   PeptideAtlas; O15263; -.
DR   PRIDE; O15263; -.
DR   ProteomicsDB; 48551; -.
DR   Ensembl; ENST00000302247; ENSP00000303532; ENSG00000171711.
DR   Ensembl; ENST00000318157; ENSP00000424598; ENSG00000177257.
DR   Ensembl; ENST00000617136; ENSP00000479138; ENSG00000275444.
DR   Ensembl; ENST00000642856; ENSP00000496499; ENSG00000285181.
DR   Ensembl; ENST00000644124; ENSP00000493760; ENSG00000285433.
DR   GeneID; 100289462; -.
DR   GeneID; 1673; -.
DR   KEGG; hsa:100289462; -.
DR   KEGG; hsa:1673; -.
DR   UCSC; uc003wsd.4; human.
DR   CTD; 100289462; -.
DR   CTD; 1673; -.
DR   DisGeNET; 100289462; -.
DR   DisGeNET; 1673; -.
DR   EuPathDB; HostDB:ENSG00000171711.2; -.
DR   EuPathDB; HostDB:ENSG00000177257.2; -.
DR   GeneCards; DEFB4A; -.
DR   GeneCards; DEFB4B; -.
DR   HGNC; HGNC:2767; DEFB4A.
DR   HGNC; HGNC:30193; DEFB4B.
DR   MIM; 602215; gene.
DR   neXtProt; NX_O15263; -.
DR   OpenTargets; ENSG00000171711; -.
DR   OpenTargets; ENSG00000177257; -.
DR   PharmGKB; PA27249; -.
DR   eggNOG; ENOG410JJAE; Eukaryota.
DR   eggNOG; ENOG411147G; LUCA.
DR   GeneTree; ENSGT00940000160995; -.
DR   HOGENOM; HOG000015465; -.
DR   HOVERGEN; HBG004834; -.
DR   InParanoid; O15263; -.
DR   KO; K21100; -.
DR   OMA; RSGAICH; -.
DR   OrthoDB; 1584343at2759; -.
DR   PhylomeDB; O15263; -.
DR   Reactome; R-HSA-1461957; Beta defensins.
DR   Reactome; R-HSA-1461973; Defensins.
DR   EvolutionaryTrace; O15263; -.
DR   GeneWiki; Beta-defensin_2; -.
DR   PRO; PR:O15263; -.
DR   Proteomes; UP000005640; Chromosome 8.
DR   Bgee; ENSG00000171711; Expressed in 43 organ(s), highest expression level in female gonad.
DR   Genevisible; O15263; HS.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR   GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR   GO; GO:0005622; C:intracellular; IDA:UniProtKB.
DR   GO; GO:0031731; F:CCR6 chemokine receptor binding; IDA:UniProtKB.
DR   GO; GO:0042056; F:chemoattractant activity; IBA:GO_Central.
DR   GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
DR   GO; GO:0019730; P:antimicrobial humoral response; TAS:Reactome.
DR   GO; GO:0060326; P:cell chemotaxis; IBA:GO_Central.
DR   GO; GO:0006935; P:chemotaxis; IDA:UniProtKB.
DR   GO; GO:0042742; P:defense response to bacterium; IMP:MGI.
DR   GO; GO:0050829; P:defense response to Gram-negative bacterium; IDA:UniProtKB.
DR   GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB.
DR   GO; GO:0007186; P:G protein-coupled receptor signaling pathway; TAS:ProtInc.
DR   GO; GO:0006955; P:immune response; TAS:ProtInc.
DR   GO; GO:0031640; P:killing of cells of other organism; IDA:UniProtKB.
DR   InterPro; IPR001855; Defensin_beta-typ.
DR   InterPro; IPR006080; Defensin_beta/alpha.
DR   Pfam; PF00711; Defensin_beta; 1.
DR   SMART; SM00048; DEFSN; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Antibiotic; Antimicrobial; Complete proteome; Defensin;
KW   Disulfide bond; Reference proteome; Secreted; Signal.
FT   SIGNAL        1     23       {ECO:0000255}.
FT   PEPTIDE      24     64       Beta-defensin 4A.
FT                                /FTId=PRO_0000006968.
FT   DISULFID     31     60
FT   DISULFID     38     53
FT   DISULFID     43     61
FT   STRAND       25     27       {ECO:0000244|PDB:1FD4}.
FT   HELIX        28     33       {ECO:0000244|PDB:1FD3}.
FT   STRAND       37     41       {ECO:0000244|PDB:1FD3}.
FT   STRAND       48     52       {ECO:0000244|PDB:1FD3}.
FT   STRAND       53     55       {ECO:0000244|PDB:1E4Q}.
FT   STRAND       59     62       {ECO:0000244|PDB:1FD3}.
SQ   SEQUENCE   64 AA;  7038 MW;  05D6454CE7ACD10E CRC64;
     MRVLYLLFSF LFIFLMPLPG VFGGIGDPVT CLKSGAICHP VFCPRRYKQI GTCGLPGTKC
     CKKP
//