Full text data of DEFA1
DEFA1
(DEF1, DEFA2, MRS)
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Neutrophil defensin 1 (Defensin, alpha 1; HNP-1; HP-1; HP1; HP 1-56; Neutrophil defensin 2; HNP-2; HP-2; HP2; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Neutrophil defensin 1 (Defensin, alpha 1; HNP-1; HP-1; HP1; HP 1-56; Neutrophil defensin 2; HNP-2; HP-2; HP2; Flags: Precursor)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P59665
ID DEF1_HUMAN Reviewed; 94 AA.
AC P59665; P11479; Q14125; Q6EZF6;
DT 30-APR-2003, integrated into UniProtKB/Swiss-Prot.
read moreDT 30-APR-2003, sequence version 1.
DT 22-JAN-2014, entry version 117.
DE RecName: Full=Neutrophil defensin 1;
DE AltName: Full=Defensin, alpha 1;
DE AltName: Full=HNP-1;
DE Short=HP-1;
DE Short=HP1;
DE Contains:
DE RecName: Full=HP 1-56;
DE Contains:
DE RecName: Full=Neutrophil defensin 2;
DE AltName: Full=HNP-2;
DE Short=HP-2;
DE Short=HP2;
DE Flags: Precursor;
GN Name=DEFA1; Synonyms=DEF1, DEFA2, MRS;
GN and
GN Name=DEFA1B;
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].
RX PubMed=3174637; DOI=10.1073/pnas.85.19.7327;
RA Daher K.A., Lehrer R.I., Ganz T., Kronenberg M.;
RT "Isolation and characterization of human defensin cDNA clones.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:7327-7331(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3370315;
RA Mars W.M., vanTuinen P., Drabkin H.A., White J.W., Saunders G.F.;
RT "A myeloid-related sequence that localizes to human chromosome 8q21.1-
RT 22.";
RL Blood 71:1713-1719(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2918759;
RA Wiedemann L.M., Francis G.E., Lamb R.F., Burns J.H., Winnie J.N.,
RA McKenzie E.D., Birnie G.D.;
RT "Differentiation stage-specific expression of a gene during
RT granulopoiesis.";
RL Leukemia 3:227-234(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8530462; DOI=10.1074/jbc.270.51.30371;
RA Mars W.M., Patmasiriwat P., Maity T., Huff V., Weil M.M.,
RA Saunders G.F.;
RT "Inheritance of unequal numbers of the genes encoding the human
RT neutrophil defensins HP-1 and HP-3.";
RL J. Biol. Chem. 270:30371-30376(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8477861; DOI=10.1016/0014-5793(93)80122-B;
RA Linzmeier R., Michaelson D., Liu L., Ganz T.;
RT "The structure of neutrophil defensin genes.";
RL FEBS Lett. 321:267-273(1993).
RN [6]
RP ERRATUM.
RX PubMed=8325384; DOI=10.1016/0014-5793(93)81813-F;
RA Linzmeier R., Michaelson D., Liu L., Ganz T.;
RL FEBS Lett. 326:299-300(1993).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S.,
RA Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A.,
RA Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T.,
RA Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K.,
RA DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G.,
RA Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B.,
RA Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C.,
RA O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K.,
RA Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R.,
RA Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K.,
RA Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q.,
RA Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N.,
RA Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
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 [9]
RP PROTEIN SEQUENCE OF 65-94.
RX PubMed=4056036; DOI=10.1172/JCI112121;
RA Selsted M.E., Harwig S.S.L., Ganz T., Schilling J.W., Lehrer R.I.;
RT "Primary structures of three human neutrophil defensins.";
RL J. Clin. Invest. 76:1436-1439(1985).
RN [10]
RP PROTEIN SEQUENCE OF 20-34.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally
RT verified cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [11]
RP DISULFIDE BONDS.
RX PubMed=2917986;
RA Selsted M.E., Harwig S.S.L.;
RT "Determination of the disulfide array in the human defensin HNP-2. A
RT covalently cyclized peptide.";
RL J. Biol. Chem. 264:4003-4007(1989).
RN [12]
RP PROTEOLYTIC PROCESSING.
RX PubMed=2019582;
RA Bateman A., Singh A., Shustik C., Mars W.M., Solomon S.;
RT "The isolation and identification of multiple forms of the neutrophil
RT granule peptides from human leukemic cells.";
RL J. Biol. Chem. 266:7524-7530(1991).
RN [13]
RP PROTEOLYTIC PROCESSING.
RX PubMed=1339298;
RA Valore E.V., Ganz T.;
RT "Posttranslational processing of defensins in immature human myeloid
RT cells.";
RL Blood 79:1538-1544(1992).
RN [14]
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 [15]
RP ADP-RIBOSYLATION AT ARG-78 AND ARG-88 BY ART1, AND PHOSPHORYLATION AT
RP TYR-85.
RX PubMed=21904558; DOI=10.1155/2011/594723;
RA Balducci E., Bonucci A., Picchianti M., Pogni R., Talluri E.;
RT "Structural and functional consequences induced by post-translational
RT modifications in alpha-Defensins.";
RL Int. J. Pept. 2011:594723-594723(2011).
RN [16]
RP STRUCTURE BY NMR OF DEFENSIN 1.
RX PubMed=1445872; DOI=10.1021/bi00161a012;
RA Zhang X.-L., Selsted M.E., Pardi A.;
RT "NMR studies of defensin antimicrobial peptides. 1. Resonance
RT assignment and secondary structure determination of rabbit NP-2 and
RT human HNP-1.";
RL Biochemistry 31:11348-11356(1992).
RN [17]
RP STRUCTURE BY NMR OF DEFENSIN 1.
RX PubMed=1445873; DOI=10.1021/bi00161a013;
RA Pardi A., Zhang X.-L., Selsted M.E., Skalicky J.J., Yip P.F.;
RT "NMR studies of defensin antimicrobial peptides. 2. Three-dimensional
RT structures of rabbit NP-2 and human HNP-1.";
RL Biochemistry 31:11357-11364(1992).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 65-94, FUNCTION, AND SUBUNIT.
RX PubMed=17452329; DOI=10.1074/jbc.M611003200;
RA Zou G., de Leeuw E., Li C., Pazgier M., Li C., Zeng P., Lu W.-Y.,
RA Lubkowski J., Lu W.;
RT "Toward understanding the cationicity of defensins. Arg and Lys versus
RT their noncoded analogs.";
RL J. Biol. Chem. 282:19653-19665(2007).
CC -!- FUNCTION: Defensin 1 and defensin 2 have antibacterial, fungicide
CC and antiviral activities. Has antimicrobial activity against Gram-
CC negative and Gram-positive bacteria. Defensins are thought to kill
CC microbes by permeabilizing their plasma membrane.
CC -!- SUBUNIT: Dimer.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- PTM: ADP-ribosylation drastically reduces cytotoxic and
CC antibacterial activities, and enhances IL8 production.
CC -!- PTM: Phosphorylation at Tyr-85 has been found in some cancer cell
CC lines, and interferes with ADP-ribosylation.
CC -!- SIMILARITY: Belongs to the alpha-defensin family.
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DR EMBL; M21130; AAA52302.1; -; mRNA.
DR EMBL; M26602; AAA52303.1; -; mRNA.
DR EMBL; L12690; AAA36382.1; -; Genomic_DNA.
DR EMBL; X52053; CAA36280.1; -; mRNA.
DR EMBL; AF200455; AAT68875.1; -; Genomic_DNA.
DR EMBL; AF200455; AAT68878.1; -; Genomic_DNA.
DR EMBL; AF200455; AAT68879.1; -; Genomic_DNA.
DR EMBL; AF200455; AAT68880.1; -; Genomic_DNA.
DR EMBL; AF238378; AAT68883.1; -; Genomic_DNA.
DR EMBL; AF238378; AAT68884.1; -; Genomic_DNA.
DR EMBL; BC069423; AAH69423.1; -; mRNA.
DR EMBL; BC093791; AAH93791.1; -; mRNA.
DR EMBL; BC112188; AAI12189.1; -; mRNA.
DR PIR; S32499; A40499.
DR RefSeq; NP_001035965.1; NM_001042500.1.
DR RefSeq; NP_004075.1; NM_004084.3.
DR UniGene; Hs.380781; -.
DR PDB; 2KHT; NMR; -; A=65-94.
DR PDB; 2PM1; X-ray; 1.60 A; A=65-94.
DR PDB; 3GNY; X-ray; 1.56 A; A/B=65-94.
DR PDB; 3H6C; X-ray; 1.63 A; A/B=65-94.
DR PDB; 3HJ2; X-ray; 1.40 A; A/B=65-94.
DR PDB; 3HJD; X-ray; 1.65 A; A/B=65-94.
DR PDB; 3LO1; X-ray; 1.60 A; A=65-94.
DR PDB; 3LO2; X-ray; 1.56 A; A/B=65-94.
DR PDB; 3LO4; X-ray; 1.75 A; A/B=65-94.
DR PDB; 3LO6; X-ray; 1.56 A; A/B=65-94.
DR PDB; 3LO9; X-ray; 1.56 A; A/B=65-94.
DR PDB; 3LOE; X-ray; 1.56 A; A=65-94.
DR PDB; 3LVX; X-ray; 1.63 A; A/B=65-94.
DR PDB; 4DU0; X-ray; 1.90 A; A/B/C/D=65-94.
DR PDBsum; 2KHT; -.
DR PDBsum; 2PM1; -.
DR PDBsum; 3GNY; -.
DR PDBsum; 3H6C; -.
DR PDBsum; 3HJ2; -.
DR PDBsum; 3HJD; -.
DR PDBsum; 3LO1; -.
DR PDBsum; 3LO2; -.
DR PDBsum; 3LO4; -.
DR PDBsum; 3LO6; -.
DR PDBsum; 3LO9; -.
DR PDBsum; 3LOE; -.
DR PDBsum; 3LVX; -.
DR PDBsum; 4DU0; -.
DR ProteinModelPortal; P59665; -.
DR SMR; P59665; 65-94.
DR IntAct; P59665; 5.
DR MINT; MINT-6631351; -.
DR STRING; 9606.ENSP00000372126; -.
DR TCDB; 1.C.19.1.1; the defensin (defensin) family.
DR PhosphoSite; P59665; -.
DR PaxDb; P59665; -.
DR PeptideAtlas; P59665; -.
DR PRIDE; P59665; -.
DR DNASU; 1667; -.
DR Ensembl; ENST00000382679; ENSP00000372126; ENSG00000206047.
DR Ensembl; ENST00000382689; ENSP00000372136; ENSG00000240247.
DR Ensembl; ENST00000382692; ENSP00000372139; ENSG00000206047.
DR Ensembl; ENST00000535841; ENSP00000443526; ENSG00000240247.
DR GeneID; 1667; -.
DR GeneID; 728358; -.
DR KEGG; hsa:1667; -.
DR KEGG; hsa:728358; -.
DR UCSC; uc003wqv.1; human.
DR CTD; 1667; -.
DR CTD; 728358; -.
DR GeneCards; GC08M006822; -.
DR GeneCards; GC08M006843; -.
DR HGNC; HGNC:2761; DEFA1.
DR HGNC; HGNC:33596; DEFA1B.
DR HPA; CAB032548; -.
DR HPA; HPA052517; -.
DR MIM; 125220; gene.
DR neXtProt; NX_P59665; -.
DR PharmGKB; PA165585475; -.
DR eggNOG; NOG86943; -.
DR HOGENOM; HOG000233351; -.
DR HOVERGEN; HBG011703; -.
DR InParanoid; P59665; -.
DR KO; K05230; -.
DR OMA; RVWAFCC; -.
DR OrthoDB; EOG75TMFQ; -.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; DEFA1; human.
DR EvolutionaryTrace; P59665; -.
DR GeneWiki; DEFA1B; -.
DR GeneWiki; Defensin,_alpha_1; -.
DR NextBio; 6860; -.
DR PMAP-CutDB; P59665; -.
DR PRO; PR:P59665; -.
DR Bgee; P59665; -.
DR CleanEx; HS_DEFA1; -.
DR Genevestigator; P59665; -.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IEA:InterPro.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
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:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
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 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; ADP-ribosylation; Antibiotic; Antimicrobial;
KW Antiviral defense; Complete proteome; Defensin;
KW Direct protein sequencing; Disulfide bond; Fungicide; Phosphoprotein;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1 19
FT PROPEP 20 38
FT /FTId=PRO_0000006771.
FT CHAIN 39 94 HP 1-56.
FT /FTId=PRO_0000006772.
FT PEPTIDE 65 94 Neutrophil defensin 1.
FT /FTId=PRO_0000006773.
FT PEPTIDE 66 94 Neutrophil defensin 2.
FT /FTId=PRO_0000006774.
FT MOD_RES 78 78 ADP-ribosylarginine; by ART1.
FT MOD_RES 85 85 Phosphotyrosine.
FT MOD_RES 88 88 ADP-ribosylarginine; by ART1.
FT DISULFID 66 94
FT DISULFID 68 83
FT DISULFID 73 93
FT STRAND 66 72
FT STRAND 79 85
FT STRAND 88 93
SQ SEQUENCE 94 AA; 10201 MW; 0E0F8E95737396FA CRC64;
MRTLAILAAI LLVALQAQAE PLQARADEVA AAPEQIAADI PEVVVSLAWD ESLAPKHPGS
RKNMACYCRI PACIAGERRY GTCIYQGRLW AFCC
//
ID DEF1_HUMAN Reviewed; 94 AA.
AC P59665; P11479; Q14125; Q6EZF6;
DT 30-APR-2003, integrated into UniProtKB/Swiss-Prot.
read moreDT 30-APR-2003, sequence version 1.
DT 22-JAN-2014, entry version 117.
DE RecName: Full=Neutrophil defensin 1;
DE AltName: Full=Defensin, alpha 1;
DE AltName: Full=HNP-1;
DE Short=HP-1;
DE Short=HP1;
DE Contains:
DE RecName: Full=HP 1-56;
DE Contains:
DE RecName: Full=Neutrophil defensin 2;
DE AltName: Full=HNP-2;
DE Short=HP-2;
DE Short=HP2;
DE Flags: Precursor;
GN Name=DEFA1; Synonyms=DEF1, DEFA2, MRS;
GN and
GN Name=DEFA1B;
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].
RX PubMed=3174637; DOI=10.1073/pnas.85.19.7327;
RA Daher K.A., Lehrer R.I., Ganz T., Kronenberg M.;
RT "Isolation and characterization of human defensin cDNA clones.";
RL Proc. Natl. Acad. Sci. U.S.A. 85:7327-7331(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3370315;
RA Mars W.M., vanTuinen P., Drabkin H.A., White J.W., Saunders G.F.;
RT "A myeloid-related sequence that localizes to human chromosome 8q21.1-
RT 22.";
RL Blood 71:1713-1719(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2918759;
RA Wiedemann L.M., Francis G.E., Lamb R.F., Burns J.H., Winnie J.N.,
RA McKenzie E.D., Birnie G.D.;
RT "Differentiation stage-specific expression of a gene during
RT granulopoiesis.";
RL Leukemia 3:227-234(1989).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=8530462; DOI=10.1074/jbc.270.51.30371;
RA Mars W.M., Patmasiriwat P., Maity T., Huff V., Weil M.M.,
RA Saunders G.F.;
RT "Inheritance of unequal numbers of the genes encoding the human
RT neutrophil defensins HP-1 and HP-3.";
RL J. Biol. Chem. 270:30371-30376(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8477861; DOI=10.1016/0014-5793(93)80122-B;
RA Linzmeier R., Michaelson D., Liu L., Ganz T.;
RT "The structure of neutrophil defensin genes.";
RL FEBS Lett. 321:267-273(1993).
RN [6]
RP ERRATUM.
RX PubMed=8325384; DOI=10.1016/0014-5793(93)81813-F;
RA Linzmeier R., Michaelson D., Liu L., Ganz T.;
RL FEBS Lett. 326:299-300(1993).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S.,
RA Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A.,
RA Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X.,
RA Allen N.R., Anderson S., Asakawa T., Blechschmidt K., Bloom T.,
RA Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K.,
RA DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G.,
RA Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B.,
RA Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C.,
RA O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K.,
RA Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R.,
RA Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K.,
RA Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q.,
RA Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N.,
RA Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Liver;
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 [9]
RP PROTEIN SEQUENCE OF 65-94.
RX PubMed=4056036; DOI=10.1172/JCI112121;
RA Selsted M.E., Harwig S.S.L., Ganz T., Schilling J.W., Lehrer R.I.;
RT "Primary structures of three human neutrophil defensins.";
RL J. Clin. Invest. 76:1436-1439(1985).
RN [10]
RP PROTEIN SEQUENCE OF 20-34.
RX PubMed=15340161; DOI=10.1110/ps.04682504;
RA Zhang Z., Henzel W.J.;
RT "Signal peptide prediction based on analysis of experimentally
RT verified cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [11]
RP DISULFIDE BONDS.
RX PubMed=2917986;
RA Selsted M.E., Harwig S.S.L.;
RT "Determination of the disulfide array in the human defensin HNP-2. A
RT covalently cyclized peptide.";
RL J. Biol. Chem. 264:4003-4007(1989).
RN [12]
RP PROTEOLYTIC PROCESSING.
RX PubMed=2019582;
RA Bateman A., Singh A., Shustik C., Mars W.M., Solomon S.;
RT "The isolation and identification of multiple forms of the neutrophil
RT granule peptides from human leukemic cells.";
RL J. Biol. Chem. 266:7524-7530(1991).
RN [13]
RP PROTEOLYTIC PROCESSING.
RX PubMed=1339298;
RA Valore E.V., Ganz T.;
RT "Posttranslational processing of defensins in immature human myeloid
RT cells.";
RL Blood 79:1538-1544(1992).
RN [14]
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 [15]
RP ADP-RIBOSYLATION AT ARG-78 AND ARG-88 BY ART1, AND PHOSPHORYLATION AT
RP TYR-85.
RX PubMed=21904558; DOI=10.1155/2011/594723;
RA Balducci E., Bonucci A., Picchianti M., Pogni R., Talluri E.;
RT "Structural and functional consequences induced by post-translational
RT modifications in alpha-Defensins.";
RL Int. J. Pept. 2011:594723-594723(2011).
RN [16]
RP STRUCTURE BY NMR OF DEFENSIN 1.
RX PubMed=1445872; DOI=10.1021/bi00161a012;
RA Zhang X.-L., Selsted M.E., Pardi A.;
RT "NMR studies of defensin antimicrobial peptides. 1. Resonance
RT assignment and secondary structure determination of rabbit NP-2 and
RT human HNP-1.";
RL Biochemistry 31:11348-11356(1992).
RN [17]
RP STRUCTURE BY NMR OF DEFENSIN 1.
RX PubMed=1445873; DOI=10.1021/bi00161a013;
RA Pardi A., Zhang X.-L., Selsted M.E., Skalicky J.J., Yip P.F.;
RT "NMR studies of defensin antimicrobial peptides. 2. Three-dimensional
RT structures of rabbit NP-2 and human HNP-1.";
RL Biochemistry 31:11357-11364(1992).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 65-94, FUNCTION, AND SUBUNIT.
RX PubMed=17452329; DOI=10.1074/jbc.M611003200;
RA Zou G., de Leeuw E., Li C., Pazgier M., Li C., Zeng P., Lu W.-Y.,
RA Lubkowski J., Lu W.;
RT "Toward understanding the cationicity of defensins. Arg and Lys versus
RT their noncoded analogs.";
RL J. Biol. Chem. 282:19653-19665(2007).
CC -!- FUNCTION: Defensin 1 and defensin 2 have antibacterial, fungicide
CC and antiviral activities. Has antimicrobial activity against Gram-
CC negative and Gram-positive bacteria. Defensins are thought to kill
CC microbes by permeabilizing their plasma membrane.
CC -!- SUBUNIT: Dimer.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- PTM: ADP-ribosylation drastically reduces cytotoxic and
CC antibacterial activities, and enhances IL8 production.
CC -!- PTM: Phosphorylation at Tyr-85 has been found in some cancer cell
CC lines, and interferes with ADP-ribosylation.
CC -!- SIMILARITY: Belongs to the alpha-defensin family.
CC -----------------------------------------------------------------------
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DR EMBL; M21130; AAA52302.1; -; mRNA.
DR EMBL; M26602; AAA52303.1; -; mRNA.
DR EMBL; L12690; AAA36382.1; -; Genomic_DNA.
DR EMBL; X52053; CAA36280.1; -; mRNA.
DR EMBL; AF200455; AAT68875.1; -; Genomic_DNA.
DR EMBL; AF200455; AAT68878.1; -; Genomic_DNA.
DR EMBL; AF200455; AAT68879.1; -; Genomic_DNA.
DR EMBL; AF200455; AAT68880.1; -; Genomic_DNA.
DR EMBL; AF238378; AAT68883.1; -; Genomic_DNA.
DR EMBL; AF238378; AAT68884.1; -; Genomic_DNA.
DR EMBL; BC069423; AAH69423.1; -; mRNA.
DR EMBL; BC093791; AAH93791.1; -; mRNA.
DR EMBL; BC112188; AAI12189.1; -; mRNA.
DR PIR; S32499; A40499.
DR RefSeq; NP_001035965.1; NM_001042500.1.
DR RefSeq; NP_004075.1; NM_004084.3.
DR UniGene; Hs.380781; -.
DR PDB; 2KHT; NMR; -; A=65-94.
DR PDB; 2PM1; X-ray; 1.60 A; A=65-94.
DR PDB; 3GNY; X-ray; 1.56 A; A/B=65-94.
DR PDB; 3H6C; X-ray; 1.63 A; A/B=65-94.
DR PDB; 3HJ2; X-ray; 1.40 A; A/B=65-94.
DR PDB; 3HJD; X-ray; 1.65 A; A/B=65-94.
DR PDB; 3LO1; X-ray; 1.60 A; A=65-94.
DR PDB; 3LO2; X-ray; 1.56 A; A/B=65-94.
DR PDB; 3LO4; X-ray; 1.75 A; A/B=65-94.
DR PDB; 3LO6; X-ray; 1.56 A; A/B=65-94.
DR PDB; 3LO9; X-ray; 1.56 A; A/B=65-94.
DR PDB; 3LOE; X-ray; 1.56 A; A=65-94.
DR PDB; 3LVX; X-ray; 1.63 A; A/B=65-94.
DR PDB; 4DU0; X-ray; 1.90 A; A/B/C/D=65-94.
DR PDBsum; 2KHT; -.
DR PDBsum; 2PM1; -.
DR PDBsum; 3GNY; -.
DR PDBsum; 3H6C; -.
DR PDBsum; 3HJ2; -.
DR PDBsum; 3HJD; -.
DR PDBsum; 3LO1; -.
DR PDBsum; 3LO2; -.
DR PDBsum; 3LO4; -.
DR PDBsum; 3LO6; -.
DR PDBsum; 3LO9; -.
DR PDBsum; 3LOE; -.
DR PDBsum; 3LVX; -.
DR PDBsum; 4DU0; -.
DR ProteinModelPortal; P59665; -.
DR SMR; P59665; 65-94.
DR IntAct; P59665; 5.
DR MINT; MINT-6631351; -.
DR STRING; 9606.ENSP00000372126; -.
DR TCDB; 1.C.19.1.1; the defensin (defensin) family.
DR PhosphoSite; P59665; -.
DR PaxDb; P59665; -.
DR PeptideAtlas; P59665; -.
DR PRIDE; P59665; -.
DR DNASU; 1667; -.
DR Ensembl; ENST00000382679; ENSP00000372126; ENSG00000206047.
DR Ensembl; ENST00000382689; ENSP00000372136; ENSG00000240247.
DR Ensembl; ENST00000382692; ENSP00000372139; ENSG00000206047.
DR Ensembl; ENST00000535841; ENSP00000443526; ENSG00000240247.
DR GeneID; 1667; -.
DR GeneID; 728358; -.
DR KEGG; hsa:1667; -.
DR KEGG; hsa:728358; -.
DR UCSC; uc003wqv.1; human.
DR CTD; 1667; -.
DR CTD; 728358; -.
DR GeneCards; GC08M006822; -.
DR GeneCards; GC08M006843; -.
DR HGNC; HGNC:2761; DEFA1.
DR HGNC; HGNC:33596; DEFA1B.
DR HPA; CAB032548; -.
DR HPA; HPA052517; -.
DR MIM; 125220; gene.
DR neXtProt; NX_P59665; -.
DR PharmGKB; PA165585475; -.
DR eggNOG; NOG86943; -.
DR HOGENOM; HOG000233351; -.
DR HOVERGEN; HBG011703; -.
DR InParanoid; P59665; -.
DR KO; K05230; -.
DR OMA; RVWAFCC; -.
DR OrthoDB; EOG75TMFQ; -.
DR Reactome; REACT_6900; Immune System.
DR ChiTaRS; DEFA1; human.
DR EvolutionaryTrace; P59665; -.
DR GeneWiki; DEFA1B; -.
DR GeneWiki; Defensin,_alpha_1; -.
DR NextBio; 6860; -.
DR PMAP-CutDB; P59665; -.
DR PRO; PR:P59665; -.
DR Bgee; P59665; -.
DR CleanEx; HS_DEFA1; -.
DR Genevestigator; P59665; -.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IEA:InterPro.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
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:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0045087; P:innate immune response; TAS:Reactome.
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 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; ADP-ribosylation; Antibiotic; Antimicrobial;
KW Antiviral defense; Complete proteome; Defensin;
KW Direct protein sequencing; Disulfide bond; Fungicide; Phosphoprotein;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1 19
FT PROPEP 20 38
FT /FTId=PRO_0000006771.
FT CHAIN 39 94 HP 1-56.
FT /FTId=PRO_0000006772.
FT PEPTIDE 65 94 Neutrophil defensin 1.
FT /FTId=PRO_0000006773.
FT PEPTIDE 66 94 Neutrophil defensin 2.
FT /FTId=PRO_0000006774.
FT MOD_RES 78 78 ADP-ribosylarginine; by ART1.
FT MOD_RES 85 85 Phosphotyrosine.
FT MOD_RES 88 88 ADP-ribosylarginine; by ART1.
FT DISULFID 66 94
FT DISULFID 68 83
FT DISULFID 73 93
FT STRAND 66 72
FT STRAND 79 85
FT STRAND 88 93
SQ SEQUENCE 94 AA; 10201 MW; 0E0F8E95737396FA CRC64;
MRTLAILAAI LLVALQAQAE PLQARADEVA AAPEQIAADI PEVVVSLAWD ESLAPKHPGS
RKNMACYCRI PACIAGERRY GTCIYQGRLW AFCC
//
MIM
125220
*RECORD*
*FIELD* NO
125220
*FIELD* TI
*125220 DEFENSIN, ALPHA, 1; DEFA1
;;DEFENSIN 1; DEF1;;
HUMAN NEUTROPHIL PEPTIDE 1; HNP1;;
read moreMYELOID-RELATED SEQUENCE; MRS
DEFENSIN, ALPHA, 2, INCLUDED; DEFA2, INCLUDED;;
HUMAN NEUTROPHIL PEPTIDE 2, INCLUDED; HNP2, INCLUDED;;
CRYPTDIN, INCLUDED;;
RETROCYCLIN, INCLUDED
*FIELD* TX
CLONING
Defensins are a group of microbicidal and cytotoxic peptides made by
neutrophils. Daher et al. (1988) stated that 3 human defensins, also
called human neutrophil peptide-1 (HNP1), HNP2, and HNP3 (604522), make
up about 30% of the neutrophil's total granule protein. From a human
promyelocytic leukemia cDNA library, Daher et al. (1988) isolated clones
encoding HNP1 and HNP3. Analysis of these clones indicated that the
defensins are made as 94-amino acid precursor proteins that must be
cleaved to yield the mature peptides. Mature HNP1 and HNP3 contain 30
amino acids each and are identical except for the N-terminal amino acid.
HNP2 may be formed by degradation or processing of HNP1 and/or HNP3,
because it lacks this N-terminal amino acid and is otherwise identical
to HNP1 and HNP3. Defensin mRNA was detected in normal bone marrow cells
but not in peripheral blood leukocytes.
Mars et al. (1987, 1988) isolated 2 overlapping cDNA clones that
represent an mRNA that is highly expressed in selected subpopulations of
myeloid leukocytes. The nucleotide sequence indicated that this
myeloid-related sequence (MRS) probably encodes a unique 93-amino acid
protein, including a leader sequence of 18 amino acids.
GENE FUNCTION
Liu et al. (1997) reported that there are 7 defensins in humans: 6
alpha-defensins and a beta-defensin (DEFB1; 602056). Neutrophil
alpha-defensins 1 to 4 (DEFA4; 601157) are found in the microbicidal
granules of neutrophils (Ganz and Lehrer, 1995) and alpha-defensins 5
(DEFA5; 600472) and 6 (DEFA6; 600471) are located in Paneth cells of the
intestinal tract. DEFB1 appears to be involved in the antimicrobial
defense of the epithelia of surfaces such as those of the respiratory
tract, urinary tract, and vagina.
In human airways, epithelial cells lining the lumen, and intraluminal
cells (e.g., polymorphonucleus cells) participate in the innate immune
response. These cells secrete or express on their surfaces
arginine-specific ADP ribosyltransferases. Defensins, antimicrobial
proteins secreted by immune cells, are arginine-rich, leading Paone et
al. (2002) to hypothesize that ADP ribosylation could modify their
biologic activities. They found that an arginine-specific ADP
ribosyltransferase-1 present on airway epithelial cells modifies arg-14
of alpha-defensin-1. ADP-ribosylated defensin-1 had decreased
antimicrobial and cytotoxic activities but still stimulated T-cell
chemotaxis and IL8 release from A549 cells. Further, ADP-ribosylated
defensin-1 inhibited cytotoxic and antimicrobial activities of
unmodified defensin-1. Paone et al. (2002) identified ADP-ribosylated
defensin-1 in bronchoalveolar lavage fluid from smokers but not from
nonsmokers, confirming its existence in vivo. Thus, airway
mono-ADP-ribosyltransferases could have an important regulatory role in
the innate immune response through modification of alpha-defensin-1 and
perhaps other basic molecules, with alteration of their biologic
properties.
The human alpha- and beta-defensin genes cluster on 8p23, a locus that
also contains the pseudogene for retrocyclin. Cole et al. (2002)
reported that human bone marrow expresses mRNA that is homologous to the
precursors of rhesus monkey circular minidefensins. Although a stop
codon within its signal sequence suggested that the human transcript now
represents an expressed pseudogene, they used its sequence and
information derived from studies on rhesus monkeys to synthesize
retrocyclin, the putative ancestral human circular minidefensin.
Retrocyclin dramatically protected human CD4(+) cells from infection by
HIV-1 in vitro, was noncytotoxic, and killed certain bacteria
effectively in physiologic saline. The authors suggested that
retrocyclin-like agents might be useful topically to prevent sexually
acquired HIV-1 infections. Cole et al. (2002) stated that it is not
possible to know whether the evolutionary loss of retrocyclin
contributed to the susceptibility of humans to HIV-1 infection.
Wang et al. (2003) stated that retrocyclin is distinct from alpha- and
beta-defensins and belongs to a third defensin subfamily, the
theta-defensins. Biacore and glycosidase analysis showed that
retrocyclin is a vertebrate lectin that binds to both O- and N-linked
sugars, including CD4 and HIV gp120 glycoproteins.
Walker et al. (1986) described an anti-HIV factor secreted by CD8 (see
186910) T cells from certain HIV-1-infected individuals in a non-major
histocompatibility complex (MHC) class I-restricted and non-cell
contact-dependent manner. The factor, referred to as CAF (CD8 antiviral
factor), is resistant to heat and acid and is of low molecular mass. CAF
is produced at relatively higher levels by clinically stable
HIV-1-infected patients, the so-called long-term nonprogressors (LTNPs),
but not by progressors. Cocchi et al. (1995) determined that the beta
chemokines CCL5 (187011), CCL4 (182284), and CCL3 (182283) possess
CAF-like activity, but only against macrophage-tropic and not
T-cell-tropic viral isolates, because of their common usage of CCR5
(601373). Using a protein chip system and mass spectrometric and protein
database analyses, Zhang et al. (2002) identified a cluster of three
3.3- to 3.5-kD proteins, DEFA1, DEFA2, and DEFA3 (604522), secreted by
LTNPs and most normal individuals, but not by progressors. DEFA1-,
DEFA2-, and DEFA3-specific antibodies depleted antiviral activity in a
dose-dependent manner, particularly against viruses using CXCR4 (162643)
rather than CCR5 as a coreceptor. Addition of synthetic or purified
natural defensins inhibited HIV-1 replication in vitro. Flow cytometric
analysis determined that in addition to neutrophils, a small population
of CD8-positive T lymphocytes harbor and secrete DEFA1, DEFA2, and
DEFA3. Zhang et al. (2002) proposed that these defensins account for
much of the anti-HIV-1 activity of CAF that is not attributable to beta
chemokines.
Chang et al. (2003) investigated whether DEFAs, particularly DEFA1,
contribute to CAF-mediated inhibition of HIV-1 transcription. They found
that DEFA1 inhibited HIV-1 infection following viral entry, but that the
DEFAs were not involved in the inhibition of HIV-1 gene expression and
long terminal repeat activation attributed to CAF derived from
herpesvirus saimiri-transformed CD8-positive cells.
Independently, Mackewicz et al. (2003) showed that DEFA1, DEFA2, and
DEFA3 exhibit anti-HIV activity by directly inactivating HIV particles
and by reducing the ability of CD4-positive T lymphocytes to replicate
the virus. Immunocytochemical and RT-PCR analysis detected expression of
DEFAs in neutrophils and monocytes, but not in CD8-positive T cells.
Antibodies specific for the DEFAs did not block the antiviral activity
of CAF-active CD8-positive cell culture fluids, indicating that,
although DEFAs possess anti-HIV effects, they are distinct from CAF.
In a retraction based upon RT-PCR analysis and careful dissection of
their cell culture system, Zhang et al. (2002) concluded that their
initial interpretation of a possible CD8-positive T-lymphocyte source
for DEFAs was incorrect. CAF activity from CD8-positive cells, in the
absence of contaminating neutrophil feeder cells, could not be
attributed to DEFAs. However, neutrophil-derived DEFAs did have potent
anti-HIV-1 activity, regardless of viral strain or target cell.
Anthrax lethal toxin, a combination of the bacterium's lethal factor and
protective antigen proteins, plays a major role in anthrax pathogenesis.
Kim et al. (2005) showed that HNP1, HNP2, and HNP3 could neutralize
anthrax lethal toxin activity and protect murine macrophages in vitro
and adult mice. They proposed that these defensins have potential for
immunotherapy of anthrax.
By screening for compounds that inhibited infection by human
papillomavirus (HPV) using pseudoviruses capable of infecting HeLa
cells, Buck et al. (2006) found that DEFA1, DEFA2, DEFA3, and DEFA5 were
potent antagonists of both mucosal and cutaneous HPVs. DEFA4 was less
active, and DEFA6, DEFB1, and DEFB2 (DEFB4; 602215) showed little to no
activity. DEFA5 was particularly active against sexually transmitted HPV
types. DEFA1 and DEFA5 also inhibited HPV-mediated transduction of other
cell types. Immunofluorescent confocal microscopy revealed that
inhibition occurred at the level of virion escape from endocytic
vesicles, but not at virion binding or internalization, and
pseudoviruses remained susceptible for many hours after initial binding
to cells. Mutant DEFA2 peptides with lower antibacterial activity that
wildtype DEFA2 retained anti-HPV effects, suggesting that its
incorporation in a topical microbicide could augment innate defenses in
the vaginal tract without disrupting the normal flora.
Using ELISA and real-time PCR, Sthoeger et al. (2008) found that HBD2
(DEFB4) was undetectable in sera from systemic lupus erythematosus (SLE;
152700) patients and that HBD2 mRNA was low in whole blood from SLE
patients, similar to controls. In contrast, DEFA2 levels were
significantly higher in all SLE patients compared with controls, and 60%
of patients had very high serum levels. High DEFA2 levels correlated
with disease activity, but not with neutrophil numbers, suggesting that
neutrophil degranulation may lead to alpha-defensin secretion in SLE
patients. Reduction of DEFA2 levels to the normal range correlated with
disease improvement.
MAPPING
Cryptdin is a defensin-related peptide that is expressed in epithelial
cells of intestinal crypts; hence, its name. Using Southern blot
analysis of DNAs from mouse/hamster somatic cell hybrids and analysis of
strain distribution pattern in recombinant inbred strains, Ouellette et
al. (1989) showed that the murine cryptdin locus (Defcr) is located on
chromosome 8. Other genes located on human 8p are found on mouse
chromosome 8.
Ouellette and Lualdi (1990) identified a related mouse locus, Crs1c
(Defcr-rs1), on chromosome 8.
Sparkes et al. (1989) used a cDNA insert for defensin HNP1 to map the
gene to human chromosome 8p23, using a mouse/human somatic cell hybrid
panel and in situ hybridization to normal human metaphase chromosomes.
Because of the close similarity between HNP1 defensin and other
defensins, they suspected that 2 or more of these genes may map to the
8p23 region.
The MRS gene was localized by Mars et al. (1987, 1988) to chromosome 8
by Southern analysis of somatic cell hybrid DNAs and was regionalized to
8q21.1-q23 by in situ hybridization to metaphase chromosomes.
CYTOGENETICS
As the breakpoint of a reciprocal translocation involving chromosomes 8
and 21 occurs at 8q22 in the form of myeloid leukemia known as ANLL-M2,
MRS may be of pathologic interest. Mars et al. (1988) found that when
Southern blot hybridization is performed by using somatic cell hybrid
DNAs harboring either a single 8q- or a single 21q+ chromosome from 2
different patients with M2-ANLL, a signal was detected only in the
hybrid containing the 8q- chromosome. See review by Lehrer et al.
(1991).
MOLECULAR GENETICS
Aldred et al. (2005) identified variation in both number and position of
DEFA1 and DEFA3 genes in arrays of 19-kb tandem repeats on chromosome
8p23.1, so that the DEFA1 and DEFA3 genes appeared to be interchangeable
variant cassettes within tandem gene arrays. The total number of gene
copies per diploid genome varied between 4 and 11 in a sample of 111
control individuals from the U.K., with approximately 10% of people
lacking DEFA3 completely. DEFA1 appeared to be at high copy number in
all great apes studied; at 1 variable site in the repeat unit, both
variants have persisted in humans, chimpanzees, and gorillas since their
divergence. Analysis of expression levels in human white blood cells
showed a clear correlation between the relative proportions of
DEFA1:DEFA3 mRNA and corresponding gene numbers. However, there was no
relationship between total (DEFA1+DEFA3) mRNA levels and total gene copy
number, suggesting the superimposed influence of trans-acting factors.
Due to the persistence of DEFA1 at high copy number in other apes,
Aldred et al. (2005) suggested an alternative model for the early stages
of the evolution of novel genes by duplication and divergence.
*FIELD* RF
1. Aldred, P. M. R.; Hollox, E. J.; Armour, J. A. L.: Copy number
polymorphism and expression level variation of the human alpha-defensin
genes DEFA1 and DEFA3. Hum. Molec. Genet. 14: 2045-2052, 2005.
2. Buck, C. B.; Day, P. M.; Thompson, C. D.; Lubkowski, J.; Lu, W.;
Lowy, D. R.; Schiller, J. T.: Human alpha-defensins block papillomavirus
infection. Proc. Nat. Acad. Sci. 103: 1516-1521, 2006.
3. Chang, T. L.-Y.; Francois, F.; Mosoian, A.; Klotman, M. E.: CAF-mediated
human immunodeficiency virus (HIV) type 1 transcriptional inhibition
is distinct from alpha-defensin-1 HIV inhibition. J. Virol. 77:
6777-6784, 2003.
4. Cocchi, F.; DeVico, A. L.; Garzino-Demo, A.; Arya, S. K.; Gallo,
R. C.; Lusso, P.: Identification of RANTES, MIP-1-alpha and MIP-1-beta
as the major HIV-suppressive factors produced by CD8+ T cells. Science 270:
1811-1815, 1995.
5. Cole, A. M.; Hong, T.; Boo, L. M.; Nguyen, T.; Zhao, C.; Bristol,
G.; Zack, J. A.; Waring, A. J.; Yang, O. O.; Lehrer, R. I.: Retrocyclin:
a primate peptide that protects cells from infection by T- and M-tropic
strains of HIV-1. Proc. Nat. Acad. Sci. 99: 1813-1818, 2002.
6. Daher, K. A.; Lehrer, R. I.; Ganz, T.; Kronenberg, M.: Isolation
and characterization of human defensin cDNA clones. Proc. Nat. Acad.
Sci. 85: 7327-7331, 1988. Note: Erratum: Proc. Nat. Acad. Sci. 86:
342 only, 1989.
7. Ganz, T.; Lehrer, R. I.: Defensins. Pharm. Ther. 66: 191-205,
1995.
8. Kim, C.; Gajendran, N.; Mittrucker, H.-W.; Weiwad, M.; Song, Y.-H.;
Hurwitz, R.; Wilmanns, M.; Fischer, G.; Kaufmann, S. H. E.: Human
alpha-defensins neutralize anthrax lethal toxin and protect against
its fatal consequences. Proc. Nat. Acad. Sci. 102: 4830-4835, 2005.
9. Lehrer, R. I.; Ganz, T.; Selsted, M. E.: Defensins: endogenous
antibiotic peptides of animal cells. Cell 64: 229-230, 1991.
10. Liu, L.; Zhao, C.; Heng, H. H. Q.; Ganz, T.: The human beta-defensin-1
and alpha-defensins are encoded by adjacent genes: two peptide families
with differing disulfide topology share a common ancestry. Genomics 43:
316-320, 1997.
11. Mackewicz, C. E.; Yuan, J.; Tran, P.; Diaz, L.; Mack, E.; Selsted,
M. E.; Levy, J. A.: Alpha-defensins can have anti-HIV activity but
are not CD8 cell anti-HIV factors. AIDS 17: F23-F32, 2003. Note:
Erratum: AIDS 17: F31 only, 2003.
12. Mars, W. M.; vanTuinen, P.; Drabkin, H. A.; White, J. W.; Saunders,
G. F.: A myeloid-related sequence that localizes to human chromosome
8q21.1-q22. Blood 71: 1713-1719, 1988.
13. Mars, W. M.; vanTuinen, P.; Ledbetter, D. H.; Saunders, G. F.
: A myeloid-related sequence that localizes to human chromosome 8q21.1-23.
(Abstract) Am. J. Hum. Genet. 41: A176 only, 1987.
14. Ouellette, A. J.; Lualdi, J. C.: A novel mouse gene family coding
for cationic, cysteine-rich peptides: regulation in small intestine
and cells of myeloid origin. J. Biol. Chem. 265: 9831-9837, 1990.
Note: Erratum: J. Biol. Chem. 269: 18702 only, 1994.
15. Ouellette, A. J.; Pravtcheva, D.; Ruddle, F. H.; James, M.: Localization
of the cryptdin locus on mouse chromosome 8. Genomics 5: 233-239,
1989. Note: Erratum: Genomics 12: 626 only, 1992.
16. Paone, G.; Wada, A.; Stevens, L. A.; Matin, A.; Hirayama, T.;
Levine, R. L.; Moss, J.: ADP ribosylation of human neutrophil peptide-1
regulates its biological properties. Proc. Nat. Acad. Sci. 99: 8231-8235,
2002.
17. Sparkes, R. S.; Kronenberg, M.; Heinzmann, C.; Daher, K. A.; Klisak,
I.; Ganz, T.; Mohandas, T.: Assignment of defensin gene(s) to human
chromosome 8p23. Genomics 5: 240-244, 1989.
18. Sthoeger, Z. M.; Bezalel, S.; Chapnik, N.; Asher, I.; Froy, O.
: High alpha-defensin levels in patients with systemic lupus erythematosus. Immunology 127:
116-122, 2008.
19. Walker, C. M.; Moody, D. J.; Stites, D. P.; Levy, J. A.: CD8+
lymphocytes can control HIV infection in vitro by suppressing virus
replication. Science 234: 1563-1566, 1986.
20. Wang, W.; Cole, A. M.; Hong, T.; Waring, A. J.; Lehrer, R. I.
: Retrocyclin, an antiretroviral theta-defensin, is a lectin. J.
Immun. 170: 4708-4716, 2003.
21. Zhang, L.; Yu, W.; He, T.; Yu, J.; Caffrey, R. E.; Dalmasso, E.
A.; Fu, S.; Pham, T.; Mei, J.; Ho, J. J.; Zhang, W.; Lopez, P.; Ho,
D. D.: Contribution of human alpha-defensin 1, 2, and 3 to the anti-HIV-1
activity of CD8 antiviral factor. Science 298: 995-1000, 2002. Note:
Retraction: Science 303: 467 only, 2004.
*FIELD* CN
Paul J. Converse - updated: 11/25/2009
George E. Tiller - updated: 11/18/2008
Paul J. Converse - updated: 10/17/2006
Paul J. Converse - updated: 3/24/2006
Paul J. Converse - updated: 1/11/2006
Paul J. Converse - updated: 2/13/2004
Matthew B. Gross - updated: 2/5/2004
Paul J. Converse - updated: 2/5/2004
Paul J. Converse - updated: 11/6/2002
Victor A. McKusick - updated: 7/3/2002
Victor A. McKusick - updated: 3/5/2002
Victor A. McKusick - updated: 10/8/1997
Victor A. McKusick - updated: 4/7/1997
*FIELD* CD
Victor A. McKusick: 10/12/1988
*FIELD* ED
terry: 03/14/2013
terry: 3/14/2013
terry: 11/9/2012
mgross: 12/4/2009
terry: 11/25/2009
wwang: 11/18/2008
carol: 11/3/2006
mgross: 10/20/2006
terry: 10/17/2006
mgross: 3/30/2006
terry: 3/24/2006
mgross: 1/11/2006
mgross: 2/13/2004
mgross: 2/5/2004
mgross: 11/6/2002
cwells: 7/18/2002
terry: 7/3/2002
mgross: 3/11/2002
terry: 3/5/2002
carol: 2/9/2000
alopez: 10/5/1999
mark: 10/16/1997
mark: 10/15/1997
terry: 10/8/1997
mark: 4/7/1997
terry: 4/2/1997
mark: 3/28/1995
mimadm: 4/2/1994
pfoster: 3/28/1994
warfield: 2/14/1994
supermim: 3/16/1992
carol: 2/18/1992
*RECORD*
*FIELD* NO
125220
*FIELD* TI
*125220 DEFENSIN, ALPHA, 1; DEFA1
;;DEFENSIN 1; DEF1;;
HUMAN NEUTROPHIL PEPTIDE 1; HNP1;;
read moreMYELOID-RELATED SEQUENCE; MRS
DEFENSIN, ALPHA, 2, INCLUDED; DEFA2, INCLUDED;;
HUMAN NEUTROPHIL PEPTIDE 2, INCLUDED; HNP2, INCLUDED;;
CRYPTDIN, INCLUDED;;
RETROCYCLIN, INCLUDED
*FIELD* TX
CLONING
Defensins are a group of microbicidal and cytotoxic peptides made by
neutrophils. Daher et al. (1988) stated that 3 human defensins, also
called human neutrophil peptide-1 (HNP1), HNP2, and HNP3 (604522), make
up about 30% of the neutrophil's total granule protein. From a human
promyelocytic leukemia cDNA library, Daher et al. (1988) isolated clones
encoding HNP1 and HNP3. Analysis of these clones indicated that the
defensins are made as 94-amino acid precursor proteins that must be
cleaved to yield the mature peptides. Mature HNP1 and HNP3 contain 30
amino acids each and are identical except for the N-terminal amino acid.
HNP2 may be formed by degradation or processing of HNP1 and/or HNP3,
because it lacks this N-terminal amino acid and is otherwise identical
to HNP1 and HNP3. Defensin mRNA was detected in normal bone marrow cells
but not in peripheral blood leukocytes.
Mars et al. (1987, 1988) isolated 2 overlapping cDNA clones that
represent an mRNA that is highly expressed in selected subpopulations of
myeloid leukocytes. The nucleotide sequence indicated that this
myeloid-related sequence (MRS) probably encodes a unique 93-amino acid
protein, including a leader sequence of 18 amino acids.
GENE FUNCTION
Liu et al. (1997) reported that there are 7 defensins in humans: 6
alpha-defensins and a beta-defensin (DEFB1; 602056). Neutrophil
alpha-defensins 1 to 4 (DEFA4; 601157) are found in the microbicidal
granules of neutrophils (Ganz and Lehrer, 1995) and alpha-defensins 5
(DEFA5; 600472) and 6 (DEFA6; 600471) are located in Paneth cells of the
intestinal tract. DEFB1 appears to be involved in the antimicrobial
defense of the epithelia of surfaces such as those of the respiratory
tract, urinary tract, and vagina.
In human airways, epithelial cells lining the lumen, and intraluminal
cells (e.g., polymorphonucleus cells) participate in the innate immune
response. These cells secrete or express on their surfaces
arginine-specific ADP ribosyltransferases. Defensins, antimicrobial
proteins secreted by immune cells, are arginine-rich, leading Paone et
al. (2002) to hypothesize that ADP ribosylation could modify their
biologic activities. They found that an arginine-specific ADP
ribosyltransferase-1 present on airway epithelial cells modifies arg-14
of alpha-defensin-1. ADP-ribosylated defensin-1 had decreased
antimicrobial and cytotoxic activities but still stimulated T-cell
chemotaxis and IL8 release from A549 cells. Further, ADP-ribosylated
defensin-1 inhibited cytotoxic and antimicrobial activities of
unmodified defensin-1. Paone et al. (2002) identified ADP-ribosylated
defensin-1 in bronchoalveolar lavage fluid from smokers but not from
nonsmokers, confirming its existence in vivo. Thus, airway
mono-ADP-ribosyltransferases could have an important regulatory role in
the innate immune response through modification of alpha-defensin-1 and
perhaps other basic molecules, with alteration of their biologic
properties.
The human alpha- and beta-defensin genes cluster on 8p23, a locus that
also contains the pseudogene for retrocyclin. Cole et al. (2002)
reported that human bone marrow expresses mRNA that is homologous to the
precursors of rhesus monkey circular minidefensins. Although a stop
codon within its signal sequence suggested that the human transcript now
represents an expressed pseudogene, they used its sequence and
information derived from studies on rhesus monkeys to synthesize
retrocyclin, the putative ancestral human circular minidefensin.
Retrocyclin dramatically protected human CD4(+) cells from infection by
HIV-1 in vitro, was noncytotoxic, and killed certain bacteria
effectively in physiologic saline. The authors suggested that
retrocyclin-like agents might be useful topically to prevent sexually
acquired HIV-1 infections. Cole et al. (2002) stated that it is not
possible to know whether the evolutionary loss of retrocyclin
contributed to the susceptibility of humans to HIV-1 infection.
Wang et al. (2003) stated that retrocyclin is distinct from alpha- and
beta-defensins and belongs to a third defensin subfamily, the
theta-defensins. Biacore and glycosidase analysis showed that
retrocyclin is a vertebrate lectin that binds to both O- and N-linked
sugars, including CD4 and HIV gp120 glycoproteins.
Walker et al. (1986) described an anti-HIV factor secreted by CD8 (see
186910) T cells from certain HIV-1-infected individuals in a non-major
histocompatibility complex (MHC) class I-restricted and non-cell
contact-dependent manner. The factor, referred to as CAF (CD8 antiviral
factor), is resistant to heat and acid and is of low molecular mass. CAF
is produced at relatively higher levels by clinically stable
HIV-1-infected patients, the so-called long-term nonprogressors (LTNPs),
but not by progressors. Cocchi et al. (1995) determined that the beta
chemokines CCL5 (187011), CCL4 (182284), and CCL3 (182283) possess
CAF-like activity, but only against macrophage-tropic and not
T-cell-tropic viral isolates, because of their common usage of CCR5
(601373). Using a protein chip system and mass spectrometric and protein
database analyses, Zhang et al. (2002) identified a cluster of three
3.3- to 3.5-kD proteins, DEFA1, DEFA2, and DEFA3 (604522), secreted by
LTNPs and most normal individuals, but not by progressors. DEFA1-,
DEFA2-, and DEFA3-specific antibodies depleted antiviral activity in a
dose-dependent manner, particularly against viruses using CXCR4 (162643)
rather than CCR5 as a coreceptor. Addition of synthetic or purified
natural defensins inhibited HIV-1 replication in vitro. Flow cytometric
analysis determined that in addition to neutrophils, a small population
of CD8-positive T lymphocytes harbor and secrete DEFA1, DEFA2, and
DEFA3. Zhang et al. (2002) proposed that these defensins account for
much of the anti-HIV-1 activity of CAF that is not attributable to beta
chemokines.
Chang et al. (2003) investigated whether DEFAs, particularly DEFA1,
contribute to CAF-mediated inhibition of HIV-1 transcription. They found
that DEFA1 inhibited HIV-1 infection following viral entry, but that the
DEFAs were not involved in the inhibition of HIV-1 gene expression and
long terminal repeat activation attributed to CAF derived from
herpesvirus saimiri-transformed CD8-positive cells.
Independently, Mackewicz et al. (2003) showed that DEFA1, DEFA2, and
DEFA3 exhibit anti-HIV activity by directly inactivating HIV particles
and by reducing the ability of CD4-positive T lymphocytes to replicate
the virus. Immunocytochemical and RT-PCR analysis detected expression of
DEFAs in neutrophils and monocytes, but not in CD8-positive T cells.
Antibodies specific for the DEFAs did not block the antiviral activity
of CAF-active CD8-positive cell culture fluids, indicating that,
although DEFAs possess anti-HIV effects, they are distinct from CAF.
In a retraction based upon RT-PCR analysis and careful dissection of
their cell culture system, Zhang et al. (2002) concluded that their
initial interpretation of a possible CD8-positive T-lymphocyte source
for DEFAs was incorrect. CAF activity from CD8-positive cells, in the
absence of contaminating neutrophil feeder cells, could not be
attributed to DEFAs. However, neutrophil-derived DEFAs did have potent
anti-HIV-1 activity, regardless of viral strain or target cell.
Anthrax lethal toxin, a combination of the bacterium's lethal factor and
protective antigen proteins, plays a major role in anthrax pathogenesis.
Kim et al. (2005) showed that HNP1, HNP2, and HNP3 could neutralize
anthrax lethal toxin activity and protect murine macrophages in vitro
and adult mice. They proposed that these defensins have potential for
immunotherapy of anthrax.
By screening for compounds that inhibited infection by human
papillomavirus (HPV) using pseudoviruses capable of infecting HeLa
cells, Buck et al. (2006) found that DEFA1, DEFA2, DEFA3, and DEFA5 were
potent antagonists of both mucosal and cutaneous HPVs. DEFA4 was less
active, and DEFA6, DEFB1, and DEFB2 (DEFB4; 602215) showed little to no
activity. DEFA5 was particularly active against sexually transmitted HPV
types. DEFA1 and DEFA5 also inhibited HPV-mediated transduction of other
cell types. Immunofluorescent confocal microscopy revealed that
inhibition occurred at the level of virion escape from endocytic
vesicles, but not at virion binding or internalization, and
pseudoviruses remained susceptible for many hours after initial binding
to cells. Mutant DEFA2 peptides with lower antibacterial activity that
wildtype DEFA2 retained anti-HPV effects, suggesting that its
incorporation in a topical microbicide could augment innate defenses in
the vaginal tract without disrupting the normal flora.
Using ELISA and real-time PCR, Sthoeger et al. (2008) found that HBD2
(DEFB4) was undetectable in sera from systemic lupus erythematosus (SLE;
152700) patients and that HBD2 mRNA was low in whole blood from SLE
patients, similar to controls. In contrast, DEFA2 levels were
significantly higher in all SLE patients compared with controls, and 60%
of patients had very high serum levels. High DEFA2 levels correlated
with disease activity, but not with neutrophil numbers, suggesting that
neutrophil degranulation may lead to alpha-defensin secretion in SLE
patients. Reduction of DEFA2 levels to the normal range correlated with
disease improvement.
MAPPING
Cryptdin is a defensin-related peptide that is expressed in epithelial
cells of intestinal crypts; hence, its name. Using Southern blot
analysis of DNAs from mouse/hamster somatic cell hybrids and analysis of
strain distribution pattern in recombinant inbred strains, Ouellette et
al. (1989) showed that the murine cryptdin locus (Defcr) is located on
chromosome 8. Other genes located on human 8p are found on mouse
chromosome 8.
Ouellette and Lualdi (1990) identified a related mouse locus, Crs1c
(Defcr-rs1), on chromosome 8.
Sparkes et al. (1989) used a cDNA insert for defensin HNP1 to map the
gene to human chromosome 8p23, using a mouse/human somatic cell hybrid
panel and in situ hybridization to normal human metaphase chromosomes.
Because of the close similarity between HNP1 defensin and other
defensins, they suspected that 2 or more of these genes may map to the
8p23 region.
The MRS gene was localized by Mars et al. (1987, 1988) to chromosome 8
by Southern analysis of somatic cell hybrid DNAs and was regionalized to
8q21.1-q23 by in situ hybridization to metaphase chromosomes.
CYTOGENETICS
As the breakpoint of a reciprocal translocation involving chromosomes 8
and 21 occurs at 8q22 in the form of myeloid leukemia known as ANLL-M2,
MRS may be of pathologic interest. Mars et al. (1988) found that when
Southern blot hybridization is performed by using somatic cell hybrid
DNAs harboring either a single 8q- or a single 21q+ chromosome from 2
different patients with M2-ANLL, a signal was detected only in the
hybrid containing the 8q- chromosome. See review by Lehrer et al.
(1991).
MOLECULAR GENETICS
Aldred et al. (2005) identified variation in both number and position of
DEFA1 and DEFA3 genes in arrays of 19-kb tandem repeats on chromosome
8p23.1, so that the DEFA1 and DEFA3 genes appeared to be interchangeable
variant cassettes within tandem gene arrays. The total number of gene
copies per diploid genome varied between 4 and 11 in a sample of 111
control individuals from the U.K., with approximately 10% of people
lacking DEFA3 completely. DEFA1 appeared to be at high copy number in
all great apes studied; at 1 variable site in the repeat unit, both
variants have persisted in humans, chimpanzees, and gorillas since their
divergence. Analysis of expression levels in human white blood cells
showed a clear correlation between the relative proportions of
DEFA1:DEFA3 mRNA and corresponding gene numbers. However, there was no
relationship between total (DEFA1+DEFA3) mRNA levels and total gene copy
number, suggesting the superimposed influence of trans-acting factors.
Due to the persistence of DEFA1 at high copy number in other apes,
Aldred et al. (2005) suggested an alternative model for the early stages
of the evolution of novel genes by duplication and divergence.
*FIELD* RF
1. Aldred, P. M. R.; Hollox, E. J.; Armour, J. A. L.: Copy number
polymorphism and expression level variation of the human alpha-defensin
genes DEFA1 and DEFA3. Hum. Molec. Genet. 14: 2045-2052, 2005.
2. Buck, C. B.; Day, P. M.; Thompson, C. D.; Lubkowski, J.; Lu, W.;
Lowy, D. R.; Schiller, J. T.: Human alpha-defensins block papillomavirus
infection. Proc. Nat. Acad. Sci. 103: 1516-1521, 2006.
3. Chang, T. L.-Y.; Francois, F.; Mosoian, A.; Klotman, M. E.: CAF-mediated
human immunodeficiency virus (HIV) type 1 transcriptional inhibition
is distinct from alpha-defensin-1 HIV inhibition. J. Virol. 77:
6777-6784, 2003.
4. Cocchi, F.; DeVico, A. L.; Garzino-Demo, A.; Arya, S. K.; Gallo,
R. C.; Lusso, P.: Identification of RANTES, MIP-1-alpha and MIP-1-beta
as the major HIV-suppressive factors produced by CD8+ T cells. Science 270:
1811-1815, 1995.
5. Cole, A. M.; Hong, T.; Boo, L. M.; Nguyen, T.; Zhao, C.; Bristol,
G.; Zack, J. A.; Waring, A. J.; Yang, O. O.; Lehrer, R. I.: Retrocyclin:
a primate peptide that protects cells from infection by T- and M-tropic
strains of HIV-1. Proc. Nat. Acad. Sci. 99: 1813-1818, 2002.
6. Daher, K. A.; Lehrer, R. I.; Ganz, T.; Kronenberg, M.: Isolation
and characterization of human defensin cDNA clones. Proc. Nat. Acad.
Sci. 85: 7327-7331, 1988. Note: Erratum: Proc. Nat. Acad. Sci. 86:
342 only, 1989.
7. Ganz, T.; Lehrer, R. I.: Defensins. Pharm. Ther. 66: 191-205,
1995.
8. Kim, C.; Gajendran, N.; Mittrucker, H.-W.; Weiwad, M.; Song, Y.-H.;
Hurwitz, R.; Wilmanns, M.; Fischer, G.; Kaufmann, S. H. E.: Human
alpha-defensins neutralize anthrax lethal toxin and protect against
its fatal consequences. Proc. Nat. Acad. Sci. 102: 4830-4835, 2005.
9. Lehrer, R. I.; Ganz, T.; Selsted, M. E.: Defensins: endogenous
antibiotic peptides of animal cells. Cell 64: 229-230, 1991.
10. Liu, L.; Zhao, C.; Heng, H. H. Q.; Ganz, T.: The human beta-defensin-1
and alpha-defensins are encoded by adjacent genes: two peptide families
with differing disulfide topology share a common ancestry. Genomics 43:
316-320, 1997.
11. Mackewicz, C. E.; Yuan, J.; Tran, P.; Diaz, L.; Mack, E.; Selsted,
M. E.; Levy, J. A.: Alpha-defensins can have anti-HIV activity but
are not CD8 cell anti-HIV factors. AIDS 17: F23-F32, 2003. Note:
Erratum: AIDS 17: F31 only, 2003.
12. Mars, W. M.; vanTuinen, P.; Drabkin, H. A.; White, J. W.; Saunders,
G. F.: A myeloid-related sequence that localizes to human chromosome
8q21.1-q22. Blood 71: 1713-1719, 1988.
13. Mars, W. M.; vanTuinen, P.; Ledbetter, D. H.; Saunders, G. F.
: A myeloid-related sequence that localizes to human chromosome 8q21.1-23.
(Abstract) Am. J. Hum. Genet. 41: A176 only, 1987.
14. Ouellette, A. J.; Lualdi, J. C.: A novel mouse gene family coding
for cationic, cysteine-rich peptides: regulation in small intestine
and cells of myeloid origin. J. Biol. Chem. 265: 9831-9837, 1990.
Note: Erratum: J. Biol. Chem. 269: 18702 only, 1994.
15. Ouellette, A. J.; Pravtcheva, D.; Ruddle, F. H.; James, M.: Localization
of the cryptdin locus on mouse chromosome 8. Genomics 5: 233-239,
1989. Note: Erratum: Genomics 12: 626 only, 1992.
16. Paone, G.; Wada, A.; Stevens, L. A.; Matin, A.; Hirayama, T.;
Levine, R. L.; Moss, J.: ADP ribosylation of human neutrophil peptide-1
regulates its biological properties. Proc. Nat. Acad. Sci. 99: 8231-8235,
2002.
17. Sparkes, R. S.; Kronenberg, M.; Heinzmann, C.; Daher, K. A.; Klisak,
I.; Ganz, T.; Mohandas, T.: Assignment of defensin gene(s) to human
chromosome 8p23. Genomics 5: 240-244, 1989.
18. Sthoeger, Z. M.; Bezalel, S.; Chapnik, N.; Asher, I.; Froy, O.
: High alpha-defensin levels in patients with systemic lupus erythematosus. Immunology 127:
116-122, 2008.
19. Walker, C. M.; Moody, D. J.; Stites, D. P.; Levy, J. A.: CD8+
lymphocytes can control HIV infection in vitro by suppressing virus
replication. Science 234: 1563-1566, 1986.
20. Wang, W.; Cole, A. M.; Hong, T.; Waring, A. J.; Lehrer, R. I.
: Retrocyclin, an antiretroviral theta-defensin, is a lectin. J.
Immun. 170: 4708-4716, 2003.
21. Zhang, L.; Yu, W.; He, T.; Yu, J.; Caffrey, R. E.; Dalmasso, E.
A.; Fu, S.; Pham, T.; Mei, J.; Ho, J. J.; Zhang, W.; Lopez, P.; Ho,
D. D.: Contribution of human alpha-defensin 1, 2, and 3 to the anti-HIV-1
activity of CD8 antiviral factor. Science 298: 995-1000, 2002. Note:
Retraction: Science 303: 467 only, 2004.
*FIELD* CN
Paul J. Converse - updated: 11/25/2009
George E. Tiller - updated: 11/18/2008
Paul J. Converse - updated: 10/17/2006
Paul J. Converse - updated: 3/24/2006
Paul J. Converse - updated: 1/11/2006
Paul J. Converse - updated: 2/13/2004
Matthew B. Gross - updated: 2/5/2004
Paul J. Converse - updated: 2/5/2004
Paul J. Converse - updated: 11/6/2002
Victor A. McKusick - updated: 7/3/2002
Victor A. McKusick - updated: 3/5/2002
Victor A. McKusick - updated: 10/8/1997
Victor A. McKusick - updated: 4/7/1997
*FIELD* CD
Victor A. McKusick: 10/12/1988
*FIELD* ED
terry: 03/14/2013
terry: 3/14/2013
terry: 11/9/2012
mgross: 12/4/2009
terry: 11/25/2009
wwang: 11/18/2008
carol: 11/3/2006
mgross: 10/20/2006
terry: 10/17/2006
mgross: 3/30/2006
terry: 3/24/2006
mgross: 1/11/2006
mgross: 2/13/2004
mgross: 2/5/2004
mgross: 11/6/2002
cwells: 7/18/2002
terry: 7/3/2002
mgross: 3/11/2002
terry: 3/5/2002
carol: 2/9/2000
alopez: 10/5/1999
mark: 10/16/1997
mark: 10/15/1997
terry: 10/8/1997
mark: 4/7/1997
terry: 4/2/1997
mark: 3/28/1995
mimadm: 4/2/1994
pfoster: 3/28/1994
warfield: 2/14/1994
supermim: 3/16/1992
carol: 2/18/1992