DEFB1_HUMAN
ID DEFB1_HUMAN Reviewed; 68 AA.
AC P60022; Q09753;
DT 21-NOV-2003, integrated into UniProtKB/Swiss-Prot.
DT 21-NOV-2003, sequence version 1.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Beta-defensin 1;
DE Short=BD-1;
DE Short=hBD-1;
DE AltName: Full=Defensin, beta 1;
DE Flags: Precursor;
GN Name=DEFB1; Synonyms=BD1, HBD1;
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 [GENOMIC DNA / MRNA].
RX PubMed=9268634; DOI=10.1006/geno.1997.4801;
RA Liu L., Zhao C., Heng H.H.Q., Ganz T.;
RT "The human beta-defensin-1 and alpha-defensins are encoded by adjacent
RT genes: two peptide families with differing disulfide topology share a
RT common ancestry.";
RL Genomics 43:316-320(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RA Zhao C.;
RL Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RX PubMed=9070620; DOI=10.1165/ajrcmb.16.3.9070620;
RA McCray P.B. Jr., Bentley L.;
RT "Human airway epithelia express a beta-defensin.";
RL Am. J. Respir. Cell Mol. Biol. 16:343-349(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Colon, and Skin;
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 [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 33-68, PROTEIN SEQUENCE OF 33-68, SUBCELLULAR
RP LOCATION, TISSUE SPECIFICITY, AND MASS SPECTROMETRY.
RC TISSUE=Kidney, Plasma, and Vagina;
RX PubMed=7628632; DOI=10.1016/0014-5793(95)00687-5;
RA Bensch K.W., Raida M., Maegert H.-J., Schulz-Knappe P., Forssmann W.-G.;
RT "hBD-1: a novel beta-defensin from human plasma.";
RL FEBS Lett. 368:331-335(1995).
RN [6]
RP SYNTHESIS OF 33-68.
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, TISSUE SPECIFICITY, AND BINDING TO CCR6.
RX PubMed=25122636; DOI=10.1126/scitranslmed.3009071;
RA Diao R., Fok K.L., Chen H., Yu M.K., Duan Y., Chung C.M., Li Z., Wu H.,
RA Li Z., Zhang H., Ji Z., Zhen W., Ng C.F., Gui Y., Cai Z., Chan H.C.;
RT "Deficient human beta-defensin 1 underlies male infertility associated with
RT poor sperm motility and genital tract infection.";
RL Sci. Transl. Med. 6:249RA108-249RA108(2014).
RN [8]
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=23938203; DOI=10.1016/j.jmb.2013.08.001;
RA De Paula V.S., Gomes N.S., Lima L.G., Miyamoto C.A., Monteiro R.Q.,
RA Almeida F.C., Valente A.P.;
RT "Structural basis for the interaction of human beta-defensin 6 and its
RT putative chemokine receptor CCR2 and breast cancer microvesicles.";
RL J. Mol. Biol. 425:4479-4495(2013).
RN [9]
RP CLEAVAGE OF SIGNAL PEPTIDE [LARGE SCALE ANALYSIS] AFTER GLY-21, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25944712; DOI=10.1002/pmic.201400617;
RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D.,
RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.;
RT "N-terminome analysis of the human mitochondrial proteome.";
RL Proteomics 15:2519-2524(2015).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (1.2 ANGSTROMS) OF 33-68.
RX PubMed=11486002; DOI=10.1074/jbc.m103830200;
RA Hoover D.M., Chertov O., Lubkowski J.;
RT "The structure of human beta-defensin-1: new insights into structural
RT properties of beta-defensins.";
RL J. Biol. Chem. 276:39021-39026(2001).
RN [11]
RP STRUCTURE BY NMR OF 33-68.
RX PubMed=11714914; DOI=10.1110/ps.24401;
RA Bauer F., Schweimer K., Kluever E., Conejo-Garcia J.-R., Forssmann W.-G.,
RA 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: Has bactericidal activity. May act as a ligand for C-C
CC chemokine receptor CCR6. Positively regulates the sperm motility and
CC bactericidal activity in a CCR6-dependent manner. Binds to CCR6 and
CC triggers Ca2+ mobilization in the sperm which is important for its
CC motility (PubMed:25122636). {ECO:0000269|PubMed:25122636}.
CC -!- SUBUNIT: Monomer (PubMed:23938203). Homodimer (PubMed:23938203).
CC {ECO:0000269|PubMed:23938203}.
CC -!- INTERACTION:
CC P60022; Q12797-6: ASPH; NbExp=3; IntAct=EBI-7200390, EBI-12092171;
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:7628632}. Membrane
CC {ECO:0000269|PubMed:23938203}. Note=Associates with tumor cell
CC membrane-derived microvesicles (PubMed:23938203).
CC {ECO:0000269|PubMed:23938203}.
CC -!- TISSUE SPECIFICITY: Blood plasma. Sperm. Highly expressed in the lower
CC head and midpiece of sperm. Significantly reduced levels found in the
CC sperms of asthenozoospermia and leukocytospermia patients (at protein
CC level). {ECO:0000269|PubMed:25122636, ECO:0000269|PubMed:7628632}.
CC -!- MASS SPECTROMETRY: Mass=3928; Mass_error=0.5; Method=Electrospray;
CC Evidence={ECO:0000269|PubMed:7628632};
CC -!- SIMILARITY: Belongs to the beta-defensin family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/DEFB1ID44352ch8p23.html";
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DR EMBL; U50931; AAC51728.1; -; Genomic_DNA.
DR EMBL; U50930; AAC51728.1; JOINED; Genomic_DNA.
DR EMBL; X92744; CAA63405.1; -; mRNA.
DR EMBL; U73945; AAB49758.1; -; mRNA.
DR EMBL; BC033298; AAH33298.1; -; mRNA.
DR EMBL; BC047677; AAH47677.1; -; mRNA.
DR EMBL; Z50788; CAA90650.1; -; mRNA.
DR CCDS; CCDS5959.1; -.
DR PIR; S66282; S66282.
DR RefSeq; NP_005209.1; NM_005218.3.
DR PDB; 1E4S; NMR; -; A=33-68.
DR PDB; 1IJU; X-ray; 1.40 A; A/B/C/D=33-68.
DR PDB; 1IJV; X-ray; 1.20 A; A/B=33-68.
DR PDB; 1KJ5; NMR; -; A=33-68.
DR PDB; 2NLB; X-ray; 1.85 A; A/B/C/D=33-68.
DR PDB; 2NLC; X-ray; 1.65 A; A/B/C/D=33-68.
DR PDB; 2NLD; X-ray; 1.49 A; A/B=33-68.
DR PDB; 2NLE; X-ray; 1.35 A; A/B=33-68.
DR PDB; 2NLF; X-ray; 1.45 A; A/B=33-68.
DR PDB; 2NLG; X-ray; 1.65 A; A/B/C/D=33-68.
DR PDB; 2NLH; X-ray; 1.85 A; A/B/C/D=33-68.
DR PDB; 2NLP; X-ray; 1.85 A; A/B/C/D=33-68.
DR PDB; 2NLQ; X-ray; 1.80 A; A/B/C/D=33-68.
DR PDB; 2NLS; X-ray; 0.98 A; A=33-68.
DR PDB; 2PLZ; X-ray; 1.36 A; A=33-68.
DR PDBsum; 1E4S; -.
DR PDBsum; 1IJU; -.
DR PDBsum; 1IJV; -.
DR PDBsum; 1KJ5; -.
DR PDBsum; 2NLB; -.
DR PDBsum; 2NLC; -.
DR PDBsum; 2NLD; -.
DR PDBsum; 2NLE; -.
DR PDBsum; 2NLF; -.
DR PDBsum; 2NLG; -.
DR PDBsum; 2NLH; -.
DR PDBsum; 2NLP; -.
DR PDBsum; 2NLQ; -.
DR PDBsum; 2NLS; -.
DR PDBsum; 2PLZ; -.
DR AlphaFoldDB; P60022; -.
DR SMR; P60022; -.
DR BioGRID; 108036; 10.
DR IntAct; P60022; 11.
DR MINT; P60022; -.
DR STRING; 9606.ENSP00000297439; -.
DR TCDB; 1.C.85.1.1; the pore-forming Beta-defensin (Beta-defensin) family.
DR GlyConnect; 2922; 1 O-Linked glycan (1 site).
DR BioMuta; DEFB1; -.
DR DMDM; 38503374; -.
DR jPOST; P60022; -.
DR MassIVE; P60022; -.
DR PaxDb; P60022; -.
DR PeptideAtlas; P60022; -.
DR PRIDE; P60022; -.
DR ProteomicsDB; 57181; -.
DR Antibodypedia; 8194; 454 antibodies from 29 providers.
DR DNASU; 1672; -.
DR Ensembl; ENST00000297439.4; ENSP00000297439.3; ENSG00000164825.4.
DR Ensembl; ENST00000642865.2; ENSP00000494448.1; ENSG00000284881.2.
DR GeneID; 1672; -.
DR KEGG; hsa:1672; -.
DR MANE-Select; ENST00000297439.4; ENSP00000297439.3; NM_005218.4; NP_005209.1.
DR UCSC; uc003wqs.4; human.
DR CTD; 1672; -.
DR DisGeNET; 1672; -.
DR GeneCards; DEFB1; -.
DR HGNC; HGNC:2766; DEFB1.
DR HPA; ENSG00000164825; Group enriched (kidney, pancreas, salivary gland).
DR MIM; 602056; gene.
DR neXtProt; NX_P60022; -.
DR OpenTargets; ENSG00000164825; -.
DR PharmGKB; PA27243; -.
DR VEuPathDB; HostDB:ENSG00000164825; -.
DR eggNOG; ENOG502TDMV; Eukaryota.
DR GeneTree; ENSGT00390000017014; -.
DR HOGENOM; CLU_189296_1_0_1; -.
DR InParanoid; P60022; -.
DR OMA; SGKAKCC; -.
DR OrthoDB; 1584343at2759; -.
DR PhylomeDB; P60022; -.
DR PathwayCommons; P60022; -.
DR Reactome; R-HSA-1461957; Beta defensins.
DR Reactome; R-HSA-1461973; Defensins.
DR SignaLink; P60022; -.
DR BioGRID-ORCS; 1672; 9 hits in 1073 CRISPR screens.
DR EvolutionaryTrace; P60022; -.
DR GeneWiki; Defensin,_beta_1; -.
DR GenomeRNAi; 1672; -.
DR Pharos; P60022; Tbio.
DR PRO; PR:P60022; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; P60022; protein.
DR Bgee; ENSG00000164825; Expressed in adult mammalian kidney and 90 other tissues.
DR Genevisible; P60022; HS.
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:0019898; C:extrinsic component of membrane; IDA:UniProtKB.
DR GO; GO:0005796; C:Golgi lumen; TAS:Reactome.
DR GO; GO:1990742; C:microvesicle; IDA:UniProtKB.
DR GO; GO:0097225; C:sperm midpiece; IDA:UniProtKB.
DR GO; GO:0031731; F:CCR6 chemokine receptor binding; IDA:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
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:0035584; P:calcium-mediated signaling using intracellular calcium source; IDA:UniProtKB.
DR GO; GO:0019933; P:cAMP-mediated signaling; IDA:UniProtKB.
DR GO; GO:0006935; P:chemotaxis; TAS:ProtInc.
DR GO; GO:0042742; P:defense response to bacterium; IMP:MGI.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IMP: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:0045087; P:innate immune response; ISS:UniProtKB.
DR GO; GO:0002227; P:innate immune response in mucosa; IDA:UniProtKB.
DR GO; GO:0060474; P:positive regulation of flagellated sperm motility involved in capacitation; IMP:UniProtKB.
DR GO; GO:0009617; P:response to bacterium; IDA:UniProtKB.
DR InterPro; IPR001855; Defensin_beta-typ.
DR Pfam; PF00711; Defensin_beta; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Antibiotic; Antimicrobial; Defensin;
KW Direct protein sequencing; Disulfide bond; Membrane; Reference proteome;
KW Secreted; Signal.
FT SIGNAL 1..21
FT /evidence="ECO:0000255, ECO:0007744|PubMed:25944712"
FT PROPEP 22..32
FT /evidence="ECO:0000269|PubMed:7628632"
FT /id="PRO_0000006899"
FT PEPTIDE 33..68
FT /note="Beta-defensin 1"
FT /id="PRO_0000006900"
FT DISULFID 37..66
FT DISULFID 44..59
FT DISULFID 49..67
FT VARIANT 38
FT /note="V -> I (in dbSNP:rs2738047)"
FT /id="VAR_018405"
FT VARIANT 48
FT /note="A -> V (in dbSNP:rs1800967)"
FT /id="VAR_014925"
FT VARIANT 67
FT /note="C -> S (in dbSNP:rs1800968)"
FT /id="VAR_014926"
FT HELIX 34..40
FT /evidence="ECO:0007829|PDB:2NLS"
FT STRAND 43..47
FT /evidence="ECO:0007829|PDB:2NLS"
FT STRAND 50..52
FT /evidence="ECO:0007829|PDB:1KJ5"
FT STRAND 55..59
FT /evidence="ECO:0007829|PDB:2NLS"
FT TURN 60..63
FT /evidence="ECO:0007829|PDB:2NLS"
FT STRAND 64..67
FT /evidence="ECO:0007829|PDB:2NLS"
SQ SEQUENCE 68 AA; 7420 MW; B0AB76DEC3B14F94 CRC64;
MRTSYLLLFT LCLLLSEMAS GGNFLTGLGH RSDHYNCVSS GGQCLYSACP IFTKIQGTCY
RGKAKCCK
