DB126_HUMAN
ID DB126_HUMAN Reviewed; 111 AA.
AC Q9BYW3; Q562G3; Q9H1M5;
DT 10-OCT-2002, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 2.
DT 03-AUG-2022, entry version 130.
DE RecName: Full=Beta-defensin 126;
DE AltName: Full=Beta-defensin 26;
DE Short=DEFB-26;
DE AltName: Full=Defensin, beta 126;
DE AltName: Full=Epididymal secretory protein 13.2;
DE Short=ESP13.2;
DE AltName: Full=HBD26 {ECO:0000303|PubMed:19373462};
DE Flags: Precursor;
GN Name=DEFB126; Synonyms=C20orf8, DEFB26;
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].
RC TISSUE=Epididymis;
RX PubMed=10491631; DOI=10.1095/biolreprod61.4.965;
RA Perry A.C.F., Jones R., Moisyadi S., Coadwell W.J., Hall L.;
RT "The novel epididymal secretory protein ESP13.2 in Macaca fascicularis.";
RL Biol. Reprod. 61:965-972(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Testis;
RX PubMed=12620395; DOI=10.1016/s0888-7543(02)00034-4;
RA Rodriguez-Jimenez F.-J., Krause A., Schulz S., Forssmann W.-G.,
RA Conejo-Garcia J.-R., Schreeb R., Motzkus D.;
RT "Distribution of new human beta-defensin genes clustered on chromosome 20
RT in functionally different segments of epididymis.";
RL Genomics 81:175-183(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 3-96, AND IDENTIFICATION.
RC TISSUE=Testis;
RX PubMed=11854508; DOI=10.1073/pnas.042692699;
RA Schutte B.C., Mitros J.P., Bartlett J.A., Walters J.D., Jia H.P.,
RA Welsh M.J., Casavant T.L., McCray P.B. Jr.;
RT "Discovery of five conserved beta-defensin gene clusters using a
RT computational search strategy.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:2129-2133(2002).
RN [5]
RP TISSUE SPECIFICITY.
RX PubMed=17928628; DOI=10.1095/biolreprod.107.062760;
RA Dube E., Hermo L., Chan P.T., Cyr D.G.;
RT "Alterations in gene expression in the caput epididymides of nonobstructive
RT azoospermic men.";
RL Biol. Reprod. 78:342-351(2008).
RN [6]
RP FUNCTION.
RX PubMed=19373462; DOI=10.1007/s00253-009-1982-z;
RA Huang L., Leong S.S., Jiang R.;
RT "Soluble fusion expression and characterization of bioactive human beta-
RT defensin 26 and 27.";
RL Appl. Microbiol. Biotechnol. 84:301-308(2009).
RN [7]
RP POSSIBLE INVOLVEMENT IN INFERTILITY, AND GLYCOSYLATION.
RX PubMed=21775668; DOI=10.1126/scitranslmed.3002289;
RA Tollner T.L., Venners S.A., Hollox E.J., Yudin A.I., Liu X., Tang G.,
RA Xing H., Kays R.J., Lau T., Overstreet J.W., Xu X., Bevins C.L.,
RA Cherr G.N.;
RT "A common mutation in the defensin DEFB126 causes impaired sperm function
RT and subfertility.";
RL Sci. Transl. Med. 3:92RA65-92RA65(2011).
RN [8]
RP FUNCTION.
RX PubMed=23229569; DOI=10.1007/s00253-012-4588-9;
RA Liu H., Yu H., Gu Y., Xin A., Zhang Y., Diao H., Lin D.;
RT "Human beta-defensin DEFB126 is capable of inhibiting LPS-mediated
RT inflammation.";
RL Appl. Microbiol. Biotechnol. 97:3395-3408(2013).
RN [9]
RP POSSIBLE INVOLVEMENT IN INFERTILITY.
RX PubMed=25721098; DOI=10.1111/jcmm.12502;
RA Duan S., Shi C., Chen G., Zheng J.F., Wu B., Diao H., Ji L., Gu Y., Xin A.,
RA Wu Y., Zhou W., Miao M., Xu L., Li Z., Yuan Y., Wang P., Shi H.;
RT "Another functional frame-shift polymorphism of DEFB126 (rs11467497)
RT associated with male infertility.";
RL J. Cell. Mol. Med. 19:1077-1084(2015).
RN [10]
RP SUBCELLULAR LOCATION, GLYCOSYLATION, AND POSSIBLE INVOLVEMENT IN
RP INFERTILITY.
RX PubMed=26832966; DOI=10.1038/srep20249;
RA Xin A., Cheng L., Diao H., Wu Y., Zhou S., Shi C., Sun Y., Wang P.,
RA Duan S., Zheng J., Wu B., Yuan Y., Gu Y., Chen G., Sun X., Shi H., Tao S.,
RA Zhang Y.;
RT "Lectin binding of human sperm associates with DEFB126 mutation and serves
RT as a potential biomarker for subfertility.";
RL Sci. Rep. 6:20249-20249(2016).
CC -!- FUNCTION: Highly glycosylated atypical beta-defensin involved in
CC several aspects of sperm function. Facilitates sperm transport in the
CC female reproductive tract and contributes to sperm protection against
CC immunodetection; both functions are probably implicating the negative
CC surface charge provided by its O-linked oligosaccharides in the sperm
CC glycocalyx. Involved in binding of sperm to oviductal epithelial cells
CC to form a sperm reservoir until ovulation. Release from the sperm
CC surface during capacitation and ovaluation by an elevation of oviductal
CC fluid pH is unmasking other surface components and allows sperm to
CC penetrate the cumulus matrix and bind to the zona pellucida of the
CC oocyte (By similarity). In vitro has antimicrobial activity and may
CC inhibit LPS-mediated inflammation (PubMed:19373462, PubMed:23229569).
CC {ECO:0000250|UniProtKB:Q9BEE3, ECO:0000269|PubMed:19373462,
CC ECO:0000269|PubMed:23229569}.
CC -!- SUBUNIT: Homodimer or homooligomer; disulfide-linked.
CC {ECO:0000250|UniProtKB:Q9BEE3, ECO:0000305}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}. Note=Secreted by
CC epididymal cells and is absorbed to the surface of sperm during transit
CC through the epididymis (By similarity). Mainly located on the sperm
CC acrosome. {ECO:0000250|UniProtKB:Q9BEE3, ECO:0000269|PubMed:26832966}.
CC -!- TISSUE SPECIFICITY: High-level and epididymis-specific expression.
CC Expression is down-regulated in infertile men.
CC {ECO:0000269|PubMed:17928628}.
CC -!- PTM: O-glycosylated; glycans contain alpha(2,3)-linked sialic acids.
CC {ECO:0000269|PubMed:21775668, ECO:0000305|PubMed:26832966}.
CC -!- DISEASE: Note=May be involved in infertility. Homozygosity for
CC frameshift truncating mutations are associated with reduced sperm O-
CC linked glycan content, impaired sperm mobility and a reduced live birth
CC rate (PubMed:21775668, PubMed:25721098). However, for one common
CC mutation the change in sperm sialic acid levels has been challenged
CC (PubMed:26832966). {ECO:0000269|PubMed:21775668,
CC ECO:0000269|PubMed:25721098, ECO:0000305|PubMed:26832966}.
CC -!- SIMILARITY: Belongs to the beta-defensin family. {ECO:0000305}.
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DR EMBL; AJ236910; CAC27121.1; -; mRNA.
DR EMBL; AF525928; AAP47221.1; -; mRNA.
DR EMBL; AL360078; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AY122478; AAM93919.1; -; mRNA.
DR CCDS; CCDS12990.1; -.
DR RefSeq; NP_112193.1; NM_030931.3.
DR AlphaFoldDB; Q9BYW3; -.
DR BioGRID; 123558; 1.
DR IntAct; Q9BYW3; 1.
DR MINT; Q9BYW3; -.
DR STRING; 9606.ENSP00000371835; -.
DR BioMuta; DEFB126; -.
DR DMDM; 61252638; -.
DR MassIVE; Q9BYW3; -.
DR PaxDb; Q9BYW3; -.
DR PeptideAtlas; Q9BYW3; -.
DR PRIDE; Q9BYW3; -.
DR ProteomicsDB; 79733; -.
DR Antibodypedia; 76536; 47 antibodies from 6 providers.
DR DNASU; 81623; -.
DR Ensembl; ENST00000382398.4; ENSP00000371835.3; ENSG00000125788.6.
DR GeneID; 81623; -.
DR KEGG; hsa:81623; -.
DR MANE-Select; ENST00000382398.4; ENSP00000371835.3; NM_030931.4; NP_112193.1.
DR UCSC; uc002wcx.5; human.
DR CTD; 81623; -.
DR DisGeNET; 81623; -.
DR GeneCards; DEFB126; -.
DR HGNC; HGNC:15900; DEFB126.
DR HPA; ENSG00000125788; Tissue enriched (epididymis).
DR neXtProt; NX_Q9BYW3; -.
DR OpenTargets; ENSG00000125788; -.
DR PharmGKB; PA27246; -.
DR VEuPathDB; HostDB:ENSG00000125788; -.
DR eggNOG; ENOG502TDX7; Eukaryota.
DR GeneTree; ENSGT00390000012226; -.
DR HOGENOM; CLU_172667_1_0_1; -.
DR InParanoid; Q9BYW3; -.
DR OMA; RSEHGWV; -.
DR OrthoDB; 1608276at2759; -.
DR PhylomeDB; Q9BYW3; -.
DR PathwayCommons; Q9BYW3; -.
DR Reactome; R-HSA-1461957; Beta defensins.
DR Reactome; R-HSA-1461973; Defensins.
DR SignaLink; Q9BYW3; -.
DR BioGRID-ORCS; 81623; 8 hits in 1060 CRISPR screens.
DR GeneWiki; DEFB126; -.
DR GenomeRNAi; 81623; -.
DR Pharos; Q9BYW3; Tbio.
DR PRO; PR:Q9BYW3; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9BYW3; protein.
DR Bgee; ENSG00000125788; Expressed in cauda epididymis and 42 other tissues.
DR ExpressionAtlas; Q9BYW3; baseline and differential.
DR Genevisible; Q9BYW3; HS.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IDA:UniProtKB.
DR GO; GO:0050829; P:defense response to Gram-negative bacterium; IDA:UniProtKB.
DR GO; GO:0045087; P:innate immune response; IEA:InterPro.
DR GO; GO:0007338; P:single fertilization; IEA:UniProtKB-KW.
DR InterPro; IPR025933; Beta_defensin.
DR Pfam; PF13841; Defensin_beta_2; 1.
PE 1: Evidence at protein level;
KW Antibiotic; Antimicrobial; Cleavage on pair of basic residues; Defensin;
KW Disulfide bond; Fertilization; Reference proteome; Secreted; Signal.
FT SIGNAL 1..20
FT /evidence="ECO:0000255"
FT CHAIN 21..111
FT /note="Beta-defensin 126"
FT /id="PRO_0000436299"
FT REGION 21..63
FT /note="In vitro binds to LPS, mediates antimicrobial
FT activity and inhibits LPS-mediated inflammation"
FT /evidence="ECO:0000269|PubMed:23229569"
FT DISULFID 27..58
FT /evidence="ECO:0000250|UniProtKB:P59665"
FT DISULFID 34..52
FT /evidence="ECO:0000250|UniProtKB:P59665"
FT DISULFID 38..59
FT /evidence="ECO:0000250|UniProtKB:P59665"
FT DISULFID 72
FT /note="Interchain"
FT /evidence="ECO:0000250|UniProtKB:Q9BEE3"
FT CONFLICT 3
FT /note="S -> F (in Ref. 1; CAC27121)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 111 AA; 12174 MW; 956E77CB6812A32D CRC64;
MKSLLFTLAV FMLLAQLVSG NWYVKKCLND VGICKKKCKP EEMHVKNGWA MCGKQRDCCV
PADRRANYPV FCVQTKTTRI STVTATTATT TLMMTTASMS SMAPTPVSPT G
