DEF1_HUMAN
ID DEF1_HUMAN Reviewed; 94 AA.
AC P59665; P11479; Q14125; Q6EZF6;
DT 30-APR-2003, integrated into UniProtKB/Swiss-Prot.
DT 30-APR-2003, sequence version 1.
DT 03-AUG-2022, entry version 178.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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 8q21.1-22.";
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., Saunders G.F.;
RT "Inheritance of unequal numbers of the genes encoding the human neutrophil
RT 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 OF PUBMED:8477861.
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., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., 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., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., 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 project:
RT 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 verified
RT cleavage sites.";
RL Protein Sci. 13:2819-2824(2004).
RN [11]
RP DISULFIDE BONDS.
RX PubMed=2917986; DOI=10.1016/s0021-9258(19)84952-9;
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; DOI=10.1016/s0021-9258(20)89478-2;
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 INTERACTION WITH RETN.
RX PubMed=15064728; DOI=10.1038/sj.onc.1207126;
RA Chumakov A.M., Kubota T., Walter S., Koeffler H.P.;
RT "Identification of murine and human XCP1 genes as C/EBP-epsilon-dependent
RT members of FIZZ/Resistin gene family.";
RL Oncogene 23:3414-3425(2004).
RN [15]
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-defensins.";
RL Antimicrob. Agents Chemother. 49:269-275(2005).
RN [16]
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 [17]
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 assignment
RT and secondary structure determination of rabbit NP-2 and human HNP-1.";
RL Biochemistry 31:11348-11356(1992).
RN [18]
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 [19]
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 and
CC antiviral activities. Has antimicrobial activity against Gram-negative
CC and Gram-positive bacteria. Defensins are thought to kill microbes by
CC permeabilizing their plasma membrane. {ECO:0000269|PubMed:15616305,
CC ECO:0000269|PubMed:17452329}.
CC -!- SUBUNIT: Dimer (PubMed:17452329). Interacts with RETN
CC (PubMed:15064728). {ECO:0000269|PubMed:15064728,
CC ECO:0000269|PubMed:17452329}.
CC -!- INTERACTION:
CC P59665; Q9UHD9: UBQLN2; NbExp=3; IntAct=EBI-726336, EBI-947187;
CC PRO_0000006773; P0DTC2: S; Xeno; NbExp=3; IntAct=EBI-27090284, EBI-25474821;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- PTM: ADP-ribosylation drastically reduces cytotoxic and antibacterial
CC 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 {ECO:0000269|PubMed:21904558}.
CC -!- SIMILARITY: Belongs to the alpha-defensin family. {ECO:0000305}.
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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 CCDS; CCDS34797.1; -.
DR CCDS; CCDS43691.1; -.
DR PIR; S32499; A40499.
DR RefSeq; NP_001035965.1; NM_001042500.1.
DR RefSeq; NP_004075.1; NM_004084.3.
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 PDB; 4LB1; X-ray; 2.00 A; A/B/D/E=65-94.
DR PDB; 4LB7; X-ray; 1.90 A; A/B/D/E=65-94.
DR PDB; 4LBB; X-ray; 1.72 A; A/B=65-94.
DR PDB; 4LBF; X-ray; 1.70 A; A/B/C/D/E/F/G/H=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 PDBsum; 4LB1; -.
DR PDBsum; 4LB7; -.
DR PDBsum; 4LBB; -.
DR PDBsum; 4LBF; -.
DR AlphaFoldDB; P59665; -.
DR BMRB; P59665; -.
DR SMR; P59665; -.
DR BioGRID; 108031; 112.
DR BioGRID; 608786; 13.
DR IntAct; P59665; 96.
DR MINT; P59665; -.
DR STRING; 9606.ENSP00000372136; -.
DR TCDB; 1.C.19.1.1; the defensin (defensin) family.
DR iPTMnet; P59665; -.
DR PhosphoSitePlus; P59665; -.
DR BioMuta; DEFA1; -.
DR DMDM; 30316322; -.
DR jPOST; P59665; -.
DR MassIVE; P59665; -.
DR PaxDb; P59665; -.
DR PeptideAtlas; P59665; -.
DR PRIDE; P59665; -.
DR ProteomicsDB; 57154; -.
DR TopDownProteomics; P59665; -.
DR Antibodypedia; 74056; 14 antibodies from 3 providers.
DR Antibodypedia; 8213; 418 antibodies from 38 providers.
DR DNASU; 1667; -.
DR Ensembl; ENST00000382679.2; ENSP00000372126.2; ENSG00000206047.3.
DR Ensembl; ENST00000382689.8; ENSP00000372136.3; ENSG00000240247.8.
DR Ensembl; ENST00000382692.3; ENSP00000372139.2; ENSG00000206047.3.
DR Ensembl; ENST00000644528.1; ENSP00000496578.1; ENSG00000284983.1.
DR Ensembl; ENST00000644617.1; ENSP00000496340.1; ENSG00000285176.1.
DR Ensembl; ENST00000644834.1; ENSP00000496058.1; ENSG00000284983.1.
DR Ensembl; ENST00000645146.1; ENSP00000493747.1; ENSG00000285176.1.
DR GeneID; 1667; -.
DR GeneID; 728358; -.
DR KEGG; hsa:1667; -.
DR KEGG; hsa:728358; -.
DR MANE-Select; ENST00000382689.8; ENSP00000372136.3; NM_001042500.2; NP_001035965.1.
DR MANE-Select; ENST00000382692.3; ENSP00000372139.2; NM_004084.4; NP_004075.1.
DR UCSC; uc003wqv.2; human.
DR CTD; 1667; -.
DR CTD; 728358; -.
DR DisGeNET; 1667; -.
DR DisGeNET; 728358; -.
DR GeneCards; DEFA1; -.
DR GeneCards; DEFA1B; -.
DR HGNC; HGNC:2761; DEFA1.
DR HGNC; HGNC:33596; DEFA1B.
DR HPA; ENSG00000206047; Tissue enriched (bone).
DR HPA; ENSG00000240247; Tissue enriched (bone).
DR MIM; 125220; gene.
DR neXtProt; NX_P59665; -.
DR OpenTargets; ENSG00000206047; -.
DR OpenTargets; ENSG00000240247; -.
DR PharmGKB; PA165585475; -.
DR VEuPathDB; HostDB:ENSG00000206047; -.
DR VEuPathDB; HostDB:ENSG00000240247; -.
DR eggNOG; ENOG502T2EX; Eukaryota.
DR GeneTree; ENSGT00940000153268; -.
DR HOGENOM; CLU_160803_0_0_1; -.
DR InParanoid; P59665; -.
DR OMA; GESNAGM; -.
DR OrthoDB; 1610714at2759; -.
DR PhylomeDB; P59665; -.
DR TreeFam; TF338414; -.
DR PathwayCommons; P59665; -.
DR Reactome; R-HSA-1461973; Defensins.
DR Reactome; R-HSA-1462054; Alpha-defensins.
DR Reactome; R-HSA-6798695; Neutrophil degranulation.
DR SignaLink; P59665; -.
DR BioGRID-ORCS; 1667; 6 hits in 561 CRISPR screens.
DR BioGRID-ORCS; 728358; 3 hits in 202 CRISPR screens.
DR ChiTaRS; DEFA1B; human.
DR EvolutionaryTrace; P59665; -.
DR GeneWiki; DEFA1B; -.
DR GeneWiki; Defensin,_alpha_1; -.
DR Pharos; P59665; Tbio.
DR PRO; PR:P59665; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P59665; protein.
DR Bgee; ENSG00000206047; Expressed in right lung and 92 other tissues.
DR Genevisible; P59665; HS.
DR GO; GO:0035578; C:azurophil granule lumen; TAS:Reactome.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; HDA:BHF-UCL.
DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB.
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:0019731; P:antibacterial humoral response; IDA:UniProtKB.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
DR GO; GO:0071222; P:cellular response to lipopolysaccharide; IBA:GO_Central.
DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
DR GO; GO:0050832; P:defense response to fungus; IEA:UniProtKB-KW.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IBA:GO_Central.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IDA:UniProtKB.
DR GO; GO:0042832; P:defense response to protozoan; IMP:UniProtKB.
DR GO; GO:0051607; P:defense response to virus; IEA:UniProtKB-KW.
DR GO; GO:0006955; P:immune response; TAS:ProtInc.
DR GO; GO:0002227; P:innate immune response in mucosa; IDA:UniProtKB.
DR GO; GO:0030520; P:intracellular estrogen receptor signaling pathway; IDA:UniProtKB.
DR GO; GO:0051873; P:killing by host of symbiont cells; IDA:UniProtKB.
DR GO; GO:0031640; P:killing of cells of another organism; IDA:UniProtKB.
DR GO; GO:0051673; P:membrane disruption in another organism; IBA:GO_Central.
DR GO; GO:0052337; P:modification by host of symbiont membrane; IDA:UniProtKB.
DR GO; GO:0010818; P:T cell chemotaxis; IDA:UniProtKB.
DR InterPro; IPR016327; Alpha-defensin.
DR InterPro; IPR006081; Alpha-defensin_C.
DR InterPro; IPR002366; Alpha-defensin_propep.
DR InterPro; IPR006080; Defensin_beta/alpha.
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; Defensin; Direct protein sequencing; Disulfide bond;
KW Fungicide; Phosphoprotein; Reference proteome; Secreted; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000269|PubMed:15340161"
FT PROPEP 20..38
FT /id="PRO_0000006771"
FT CHAIN 39..94
FT /note="HP 1-56"
FT /id="PRO_0000006772"
FT PEPTIDE 65..94
FT /note="Neutrophil defensin 1"
FT /id="PRO_0000006773"
FT PEPTIDE 66..94
FT /note="Neutrophil defensin 2"
FT /id="PRO_0000006774"
FT MOD_RES 78
FT /note="ADP-ribosylarginine; by ART1"
FT /evidence="ECO:0000269|PubMed:21904558"
FT MOD_RES 85
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000269|PubMed:21904558"
FT MOD_RES 88
FT /note="ADP-ribosylarginine; by ART1"
FT /evidence="ECO:0000269|PubMed:21904558"
FT DISULFID 66..94
FT /evidence="ECO:0000269|PubMed:2917986"
FT DISULFID 68..83
FT /evidence="ECO:0000269|PubMed:2917986"
FT DISULFID 73..93
FT /evidence="ECO:0000269|PubMed:2917986"
FT STRAND 66..72
FT /evidence="ECO:0007829|PDB:3HJ2"
FT STRAND 79..85
FT /evidence="ECO:0007829|PDB:3HJ2"
FT STRAND 88..93
FT /evidence="ECO:0007829|PDB:3HJ2"
SQ SEQUENCE 94 AA; 10201 MW; 0E0F8E95737396FA CRC64;
MRTLAILAAI LLVALQAQAE PLQARADEVA AAPEQIAADI PEVVVSLAWD ESLAPKHPGS
RKNMACYCRI PACIAGERRY GTCIYQGRLW AFCC
