ID   GPX5_HUMAN              Reviewed;         221 AA.
AC   O75715; A1A4Y0;
DT   15-JUL-1999, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1998, sequence version 1.
DT   24-JAN-2024, entry version 183.
DE   RecName: Full=Epididymal secretory glutathione peroxidase;
DE            EC=1.11.1.9;
DE   AltName: Full=Epididymis-specific glutathione peroxidase-like protein;
DE            Short=EGLP;
DE   AltName: Full=Glutathione peroxidase 5;
DE            Short=GPx-5;
DE            Short=GSHPx-5;
DE   Flags: Precursor;
GN   Name=GPX5;
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] (ISOFORM 1).
RC   TISSUE=Epididymis;
RX   PubMed=9639555; DOI=10.1042/bj3330005;
RA   Hall L., Williams K., Perry A.C.F., Frayne J., Jury J.A.;
RT   "The majority of human glutathione peroxidase type 5 (GPX5) transcripts are
RT   incorrectly spliced: implications for the role of GPX5 in the male
RT   reproductive tract.";
RL   Biochem. J. 333:5-9(1998).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT VAL-85.
RG   NIEHS SNPs program;
RL   Submitted (JAN-2005) to the EMBL/GenBank/DDBJ databases.
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=14574404; DOI=10.1038/nature02055;
RA   Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA   Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA   Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA   Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA   Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA   Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA   Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA   Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA   Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA   French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA   Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA   Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA   Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA   Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA   Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA   Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA   Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA   Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA   Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA   Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA   Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA   Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA   Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA   Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA   West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA   Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA   Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA   Rogers J., Beck S.;
RT   "The DNA sequence and analysis of human chromosome 6.";
RL   Nature 425:805-811(2003).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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   [6]
RP   X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 28-220.
RG   Structural genomics consortium (SGC);
RT   "Crystal structure of human glutathione peroxidase 5.";
RL   Submitted (FEB-2009) to the PDB data bank.
CC   -!- FUNCTION: Protects cells and enzymes from oxidative damage, by
CC       catalyzing the reduction of hydrogen peroxide, lipid peroxides and
CC       organic hydroperoxide, by glutathione. May constitute a glutathione
CC       peroxidase-like protective system against peroxide damage in sperm
CC       membrane lipids.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 glutathione + H2O2 = glutathione disulfide + 2 H2O;
CC         Xref=Rhea:RHEA:16833, ChEBI:CHEBI:15377, ChEBI:CHEBI:16240,
CC         ChEBI:CHEBI:57925, ChEBI:CHEBI:58297; EC=1.11.1.9;
CC   -!- SUBCELLULAR LOCATION: Secreted.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=1;
CC         IsoId=O75715-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O75715-2; Sequence=VSP_043046;
CC   -!- TISSUE SPECIFICITY: Epididymis.
CC   -!- SIMILARITY: Belongs to the glutathione peroxidase family.
CC       {ECO:0000305}.
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="http://egp.gs.washington.edu/data/gpx5/";
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DR   EMBL; AJ005277; CAA06463.1; -; mRNA.
DR   EMBL; AY882013; AAW56939.1; -; Genomic_DNA.
DR   EMBL; AL049543; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471081; EAX03168.1; -; Genomic_DNA.
DR   EMBL; BC128159; AAI28160.1; -; mRNA.
DR   EMBL; BC128160; AAI28161.1; -; mRNA.
DR   CCDS; CCDS4652.1; -. [O75715-1]
DR   CCDS; CCDS4653.1; -. [O75715-2]
DR   RefSeq; NP_001500.1; NM_001509.2. [O75715-1]
DR   RefSeq; NP_003987.2; NM_003996.3. [O75715-2]
DR   PDB; 2I3Y; X-ray; 2.00 A; A=28-220.
DR   PDBsum; 2I3Y; -.
DR   AlphaFoldDB; O75715; -.
DR   SMR; O75715; -.
DR   IntAct; O75715; 1.
DR   STRING; 9606.ENSP00000392398; -.
DR   DrugBank; DB09096; Benzoyl peroxide.
DR   DrugBank; DB00143; Glutathione.
DR   DrugBank; DB03310; Glutathione disulfide.
DR   PeroxiBase; 3604; HsGPx05-A.
DR   PeroxiBase; 3629; HsGPx05-B.
DR   iPTMnet; O75715; -.
DR   PhosphoSitePlus; O75715; -.
DR   BioMuta; GPX5; -.
DR   MassIVE; O75715; -.
DR   PaxDb; 9606-ENSP00000392398; -.
DR   PeptideAtlas; O75715; -.
DR   ProteomicsDB; 50172; -. [O75715-1]
DR   Antibodypedia; 25906; 106 antibodies from 18 providers.
DR   DNASU; 2880; -.
DR   Ensembl; ENST00000412168.7; ENSP00000392398.2; ENSG00000224586.7. [O75715-1]
DR   Ensembl; ENST00000469384.1; ENSP00000419935.1; ENSG00000224586.7. [O75715-2]
DR   Ensembl; ENST00000550775.5; ENSP00000450365.1; ENSG00000257770.5. [O75715-1]
DR   Ensembl; ENST00000551639.1; ENSP00000449271.1; ENSG00000257770.5. [O75715-2]
DR   GeneID; 2880; -.
DR   KEGG; hsa:2880; -.
DR   MANE-Select; ENST00000412168.7; ENSP00000392398.2; NM_001509.3; NP_001500.1.
DR   UCSC; uc003nlm.3; human. [O75715-1]
DR   AGR; HGNC:4557; -.
DR   CTD; 2880; -.
DR   DisGeNET; 2880; -.
DR   GeneCards; GPX5; -.
DR   HGNC; HGNC:4557; GPX5.
DR   HPA; ENSG00000224586; Tissue enriched (epididymis).
DR   MIM; 603435; gene.
DR   neXtProt; NX_O75715; -.
DR   OpenTargets; ENSG00000224586; -.
DR   PharmGKB; PA28953; -.
DR   VEuPathDB; HostDB:ENSG00000224586; -.
DR   eggNOG; KOG1651; Eukaryota.
DR   GeneTree; ENSGT00940000164550; -.
DR   HOGENOM; CLU_029507_2_1_1; -.
DR   InParanoid; O75715; -.
DR   OMA; HELMNGI; -.
DR   OrthoDB; 67394at2759; -.
DR   PhylomeDB; O75715; -.
DR   TreeFam; TF105318; -.
DR   BRENDA; 1.11.1.9; 2681.
DR   PathwayCommons; O75715; -.
DR   Reactome; R-HSA-3299685; Detoxification of Reactive Oxygen Species.
DR   BioGRID-ORCS; 2880; 30 hits in 1145 CRISPR screens.
DR   EvolutionaryTrace; O75715; -.
DR   GeneWiki; GPX5; -.
DR   GenomeRNAi; 2880; -.
DR   Pharos; O75715; Tbio.
DR   PRO; PR:O75715; -.
DR   Proteomes; UP000005640; Chromosome 6.
DR   RNAct; O75715; Protein.
DR   Bgee; ENSG00000224586; Expressed in right testis and 16 other cell types or tissues.
DR   ExpressionAtlas; O75715; baseline and differential.
DR   GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR   GO; GO:0004602; F:glutathione peroxidase activity; IBA:GO_Central.
DR   GO; GO:0034599; P:cellular response to oxidative stress; TAS:Reactome.
DR   GO; GO:0006629; P:lipid metabolic process; NAS:ProtInc.
DR   CDD; cd00340; GSH_Peroxidase; 1.
DR   Gene3D; 3.40.30.10; Glutaredoxin; 1.
DR   InterPro; IPR000889; Glutathione_peroxidase.
DR   InterPro; IPR029759; GPX_AS.
DR   InterPro; IPR029760; GPX_CS.
DR   InterPro; IPR036249; Thioredoxin-like_sf.
DR   PANTHER; PTHR11592:SF127; EPIDIDYMAL SECRETORY GLUTATHIONE PEROXIDASE; 1.
DR   PANTHER; PTHR11592; GLUTATHIONE PEROXIDASE; 1.
DR   Pfam; PF00255; GSHPx; 1.
DR   PIRSF; PIRSF000303; Glutathion_perox; 1.
DR   PRINTS; PR01011; GLUTPROXDASE.
DR   SUPFAM; SSF52833; Thioredoxin-like; 1.
DR   PROSITE; PS00460; GLUTATHIONE_PEROXID_1; 1.
DR   PROSITE; PS00763; GLUTATHIONE_PEROXID_2; 1.
DR   PROSITE; PS51355; GLUTATHIONE_PEROXID_3; 1.
DR   Genevisible; O75715; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Oxidoreductase; Peroxidase;
KW   Reference proteome; Secreted; Signal.
FT   SIGNAL          1..21
FT                   /evidence="ECO:0000255"
FT   CHAIN           22..221
FT                   /note="Epididymal secretory glutathione peroxidase"
FT                   /id="PRO_0000013076"
FT   ACT_SITE        73
FT                   /evidence="ECO:0000250"
FT   VAR_SEQ         81..221
FT                   /note="ELNALQEELKPYGLVVLGFPCNQFGKQEPGDNKEILPGLKYVRPGGGFVPSF
FT                   QLFEKGDVNGEKEQKVFSFLKHSCPHPSEILGTFKSISWDPVKVHDIRWNFEKFLVGPD
FT                   GIPVMRWSHRATVSSVKTDILAYLKQFKTK -> GMSVQGEDLYLVSSFLRKGM (in
FT                   isoform 2)"
FT                   /evidence="ECO:0000303|PubMed:15489334"
FT                   /id="VSP_043046"
FT   VARIANT         85
FT                   /note="L -> P (in dbSNP:rs58554303)"
FT                   /id="VAR_061206"
FT   VARIANT         85
FT                   /note="L -> V (in dbSNP:rs769188)"
FT                   /evidence="ECO:0000269|Ref.2"
FT                   /id="VAR_012040"
FT   HELIX           40..42
FT                   /evidence="ECO:0007829|PDB:2I3Y"
FT   STRAND          44..51
FT                   /evidence="ECO:0007829|PDB:2I3Y"
FT   STRAND          53..55
FT                   /evidence="ECO:0007829|PDB:2I3Y"
FT   HELIX           56..59
FT                   /evidence="ECO:0007829|PDB:2I3Y"
FT   STRAND          62..69
FT                   /evidence="ECO:0007829|PDB:2I3Y"
FT   STRAND          71..73
FT                   /evidence="ECO:0007829|PDB:2I3Y"
FT   HELIX           74..78
FT                   /evidence="ECO:0007829|PDB:2I3Y"
FT   HELIX           79..89
FT                   /evidence="ECO:0007829|PDB:2I3Y"
FT   HELIX           90..92
FT                   /evidence="ECO:0007829|PDB:2I3Y"
FT   STRAND          94..100
FT                   /evidence="ECO:0007829|PDB:2I3Y"
FT   HELIX           112..114
FT                   /evidence="ECO:0007829|PDB:2I3Y"
FT   HELIX           115..121
FT                   /evidence="ECO:0007829|PDB:2I3Y"
FT   STRAND          131..135
FT                   /evidence="ECO:0007829|PDB:2I3Y"
FT   STRAND          140..142
FT                   /evidence="ECO:0007829|PDB:2I3Y"
FT   HELIX           147..155
FT                   /evidence="ECO:0007829|PDB:2I3Y"
FT   TURN            166..168
FT                   /evidence="ECO:0007829|PDB:2I3Y"
FT   STRAND          171..173
FT                   /evidence="ECO:0007829|PDB:2I3Y"
FT   STRAND          185..188
FT                   /evidence="ECO:0007829|PDB:2I3Y"
FT   STRAND          194..198
FT                   /evidence="ECO:0007829|PDB:2I3Y"
FT   HELIX           204..214
FT                   /evidence="ECO:0007829|PDB:2I3Y"
FT   HELIX           215..217
FT                   /evidence="ECO:0007829|PDB:2I3Y"
SQ   SEQUENCE   221 AA;  25202 MW;  CE3E7BFD53CE979F CRC64;
     MTTQLRVVHL LPLLLACFVQ TSPKQEKMKM DCHKDEKGTI YDYEAIALNK NEYVSFKQYV
     GKHILFVNVA TYCGLTAQYP ELNALQEELK PYGLVVLGFP CNQFGKQEPG DNKEILPGLK
     YVRPGGGFVP SFQLFEKGDV NGEKEQKVFS FLKHSCPHPS EILGTFKSIS WDPVKVHDIR
     WNFEKFLVGP DGIPVMRWSH RATVSSVKTD ILAYLKQFKT K
//