DJ1B_DROME
ID DJ1B_DROME Reviewed; 187 AA.
AC Q9VA37; Q7KXK5; Q95SP6;
DT 15-MAR-2017, integrated into UniProtKB/Swiss-Prot.
DT 11-MAY-2016, sequence version 3.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Protein dj-1beta {ECO:0000305};
GN Name=dj-1beta {ECO:0000312|FlyBase:FBgn0039802};
GN Synonyms=dj-1-beta {ECO:0000312|FlyBase:FBgn0039802};
GN ORFNames=CG1349 {ECO:0000312|FlyBase:FBgn0039802};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
RC TISSUE=Head {ECO:0000312|EMBL:BAB84672.1};
RX PubMed=15976810; DOI=10.1038/sj.cdd.4401704;
RA Shinbo Y., Niki T., Taira T., Ooe H., Takahashi-Niki K., Maita C.,
RA Seino C., Iguchi-Ariga S.M.M., Ariga H.;
RT "Proper SUMO-1 conjugation is essential to DJ-1 to exert its full
RT activities.";
RL Cell Death Differ. 13:96-108(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=Berkeley;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5]
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=16139213; DOI=10.1016/j.cub.2005.07.064;
RA Meulener M., Whitworth A.J., Armstrong-Gold C.E., Rizzu P., Heutink P.,
RA Wes P.D., Pallanck L.J., Bonini N.M.;
RT "Drosophila DJ-1 mutants are selectively sensitive to environmental toxins
RT associated with Parkinson's disease.";
RL Curr. Biol. 15:1572-1577(2005).
RN [6]
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=16139214; DOI=10.1016/j.cub.2005.07.036;
RA Menzies F.M., Yenisetti S.C., Min K.T.;
RT "Roles of Drosophila DJ-1 in survival of dopaminergic neurons and oxidative
RT stress.";
RL Curr. Biol. 15:1578-1582(2005).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=16203113; DOI=10.1016/j.gene.2005.06.040;
RA Park J., Kim S.Y., Cha G.H., Lee S.B., Kim S., Chung J.;
RT "Drosophila DJ-1 mutants show oxidative stress-sensitive locomotive
RT dysfunction.";
RL Gene 361:133-139(2005).
RN [8]
RP FUNCTION, OXIDATION AT CYS-45 AND CYS-104, AND MUTAGENESIS OF CYS-45 AND
RP CYS-104.
RX PubMed=16894167; DOI=10.1073/pnas.0601891103;
RA Meulener M.C., Xu K., Thomson L., Thompson L., Ischiropoulos H.,
RA Bonini N.M.;
RT "Mutational analysis of DJ-1 in Drosophila implicates functional
RT inactivation by oxidative damage and aging.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:12517-12522(2006).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20457924; DOI=10.1073/pnas.0911175107;
RA Hao L.Y., Giasson B.I., Bonini N.M.;
RT "DJ-1 is critical for mitochondrial function and rescues PINK1 loss of
RT function.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:9747-9752(2010).
RN [10]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23593018; DOI=10.1371/journal.pgen.1003412;
RA Hwang S., Song S., Hong Y.K., Choi G., Suh Y.S., Han S.Y., Lee M.,
RA Park S.H., Lee J.H., Lee S., Bang S.M., Jeong Y., Chung W.J., Lee I.S.,
RA Jeong G., Chung J., Cho K.S.;
RT "Drosophila DJ-1 decreases neural sensitivity to stress by negatively
RT regulating Daxx-like protein through dFOXO.";
RL PLoS Genet. 9:E1003412-E1003412(2013).
RN [11]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27903648; DOI=10.1074/jbc.m116.743823;
RA Pfaff D.H., Fleming T., Nawroth P., Teleman A.A.;
RT "Evidence against a role for the Parkinsonism-associated protein DJ-1 in
RT methylglyoxal detoxification.";
RL J. Biol. Chem. 292:685-690(2017).
RN [12]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=30540251; DOI=10.7554/elife.39393;
RA Oswald M.C., Brooks P.S., Zwart M.F., Mukherjee A., West R.J.,
RA Giachello C.N., Morarach K., Baines R.A., Sweeney S.T., Landgraf M.;
RT "Reactive oxygen species regulate activity-dependent neuronal plasticity in
RT Drosophila.";
RL Elife 7:0-0(2018).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 19-205, AND OXIDATION AT CYS-104.
RX PubMed=22515803; DOI=10.1021/bi3003296;
RA Lin J., Prahlad J., Wilson M.A.;
RT "Conservation of oxidative protein stabilization in an insect homologue of
RT parkinsonism-associated protein DJ-1.";
RL Biochemistry 51:3799-3807(2012).
CC -!- FUNCTION: Plays an important role in cell protection against oxidative
CC stress and cell death by acting as a oxidative stress sensor
CC (PubMed:16139214, PubMed:16203113, PubMed:16894167, PubMed:20457924).
CC Does not play a role in methylglyoxal detoxification (PubMed:27903648).
CC Plays a role in mitochondrial function together with Pink1
CC (PubMed:20457924). In motor neurons regulates structural synaptic
CC plasticity of locomotor behavior as part of the PTEN-
CC phosphatidylinositol 3-kinase pathway in response to oxygen species
CC (ROS) levels (PubMed:30540251). {ECO:0000269|PubMed:16139214,
CC ECO:0000269|PubMed:16203113, ECO:0000269|PubMed:16894167,
CC ECO:0000269|PubMed:20457924, ECO:0000269|PubMed:27903648,
CC ECO:0000269|PubMed:30540251}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:16203113}.
CC Cytoplasm {ECO:0000269|PubMed:16203113}. Nucleus
CC {ECO:0000269|PubMed:16203113}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9VA37-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9VA37-2; Sequence=VSP_058800;
CC -!- TISSUE SPECIFICITY: Expressed in the head and testis (at protein level)
CC (PubMed:16139213). Ubiquitously expressed at constant levels
CC (PubMed:16139214). {ECO:0000269|PubMed:16139213,
CC ECO:0000269|PubMed:16139214}.
CC -!- DEVELOPMENTAL STAGE: Detected during embryogenesis (at protein level)
CC (PubMed:16139213). Maternally contributed, after which its levels fall
CC slightly in embryo but increase again through development and in adult
CC (PubMed:16139214, PubMed:16203113). {ECO:0000269|PubMed:16139213,
CC ECO:0000269|PubMed:16139214, ECO:0000269|PubMed:16203113}.
CC -!- PTM: Oxidation of Cys-45 and Cys-104 in response to oxidative stress
CC (PubMed:16894167, PubMed:22515803). Levels of oxidation increase with
CC age (PubMed:16894167). {ECO:0000269|PubMed:16894167,
CC ECO:0000269|PubMed:22515803}.
CC -!- DISRUPTION PHENOTYPE: Viable and fertile (PubMed:16203113). Larvae
CC develop normally but show increased oxidative stress-induced cell death
CC (PubMed:23593018, PubMed:30540251). Larvae show structurally normal
CC neuromuscular junctions, however they fail to show structural synaptic
CC plasticity in response to oxygen species (ROS) levels
CC (PubMed:30540251). Adult flies show severe defects in locomotor ability
CC without loss of dopaminergic neurons and increased sensitivity to
CC oxidative stress (PubMed:16139214, PubMed:16203113, PubMed:23593018).
CC Results in altered subcellular localization of Daxx (PubMed:23593018).
CC Does not show more elevated levels of methylglyoxal adducts than
CC controls (PubMed:27903648). Double knockouts for dj-1beta and dj-1alpha
CC is viable but with reduced male fertility (PubMed:16139213,
CC PubMed:20457924). Double knockouts for dj-1beta and dj-1alpha is more
CC sensitive to chemical agents that induce oxidative stress
CC (PubMed:16139213). Double knockouts for dj-1beta and dj-1alpha shows
CC reduced lifespan and decreased spontaneous movement over time
CC (PubMed:20457924). Double knockouts for dj-1beta and dj-1alpha
CC spermatozoa are morphologically normal but immotile with abnormal
CC vacuoles in the Nebenkern, abnormal mitochondria and aberrant
CC separation of investment cones during sperm individualization
CC (PubMed:20457924). Double knockouts for DJ-1beta and Daxx restore
CC normal number of dopaminergic neurons, locomotor activity and
CC sensitivity to oxidative stress and UV-induced damage
CC (PubMed:23593018). {ECO:0000269|PubMed:16139213,
CC ECO:0000269|PubMed:16139214, ECO:0000269|PubMed:16203113,
CC ECO:0000269|PubMed:20457924, ECO:0000269|PubMed:23593018,
CC ECO:0000269|PubMed:27903648, ECO:0000269|PubMed:30540251}.
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DR EMBL; AB079599; BAB84672.1; -; mRNA.
DR EMBL; AE014297; AAF57086.3; -; Genomic_DNA.
DR EMBL; AY060670; AAL28218.1; -; mRNA.
DR RefSeq; NP_651825.4; NM_143568.3. [Q9VA37-1]
DR PDB; 4E08; X-ray; 2.00 A; A/B=1-187.
DR PDBsum; 4E08; -.
DR AlphaFoldDB; Q9VA37; -.
DR SMR; Q9VA37; -.
DR IntAct; Q9VA37; 2.
DR STRING; 7227.FBpp0085065; -.
DR MEROPS; C56.002; -.
DR PaxDb; Q9VA37; -.
DR PRIDE; Q9VA37; -.
DR DNASU; 43652; -.
DR EnsemblMetazoa; FBtr0445215; FBpp0401456; FBgn0039802. [Q9VA37-1]
DR GeneID; 43652; -.
DR KEGG; dme:Dmel_CG1349; -.
DR UCSC; CG1349-RA; d. melanogaster. [Q9VA37-1]
DR CTD; 43652; -.
DR FlyBase; FBgn0039802; dj-1beta.
DR VEuPathDB; VectorBase:FBgn0039802; -.
DR eggNOG; KOG2764; Eukaryota.
DR GeneTree; ENSGT00390000001231; -.
DR HOGENOM; CLU_000445_44_2_1; -.
DR InParanoid; Q9VA37; -.
DR OMA; TSYPAMK; -.
DR PhylomeDB; Q9VA37; -.
DR Reactome; R-DME-9646399; Aggrephagy.
DR BioGRID-ORCS; 43652; 0 hits in 1 CRISPR screen.
DR GenomeRNAi; 43652; -.
DR PRO; PR:Q9VA37; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0039802; Expressed in mouthpart and 24 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0051920; F:peroxiredoxin activity; ISS:FlyBase.
DR GO; GO:0036524; F:protein deglycase activity; ISS:FlyBase.
DR GO; GO:0008344; P:adult locomotory behavior; IMP:FlyBase.
DR GO; GO:0034614; P:cellular response to reactive oxygen species; IMP:UniProtKB.
DR GO; GO:0046295; P:glycolate biosynthetic process; IBA:GO_Central.
DR GO; GO:1903189; P:glyoxal metabolic process; IBA:GO_Central.
DR GO; GO:0008345; P:larval locomotory behavior; IMP:UniProtKB.
DR GO; GO:0048640; P:negative regulation of developmental growth; IMP:FlyBase.
DR GO; GO:1901215; P:negative regulation of neuron death; IBA:GO_Central.
DR GO; GO:0014065; P:phosphatidylinositol 3-kinase signaling; IMP:UniProtKB.
DR GO; GO:0010310; P:regulation of hydrogen peroxide metabolic process; IMP:FlyBase.
DR GO; GO:1905446; P:regulation of mitochondrial ATP synthesis coupled electron transport; IGI:FlyBase.
DR GO; GO:1900073; P:regulation of neuromuscular synaptic transmission; IMP:UniProtKB.
DR GO; GO:0048167; P:regulation of synaptic plasticity; IMP:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; IDA:FlyBase.
DR Gene3D; 3.40.50.880; -; 1.
DR InterPro; IPR029062; Class_I_gatase-like.
DR InterPro; IPR006287; DJ-1.
DR InterPro; IPR002818; DJ-1/PfpI.
DR Pfam; PF01965; DJ-1_PfpI; 1.
DR SUPFAM; SSF52317; SSF52317; 1.
DR TIGRFAMs; TIGR01383; not_thiJ; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cytoplasm; Mitochondrion; Nucleus;
KW Oxidation; Reference proteome.
FT CHAIN 1..187
FT /note="Protein dj-1beta"
FT /id="PRO_0000439172"
FT ACT_SITE 104
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:Q99497"
FT MOD_RES 45
FT /note="Cysteine sulfinic acid (-SO2H)"
FT /evidence="ECO:0000269|PubMed:16894167"
FT MOD_RES 104
FT /note="Cysteine sulfinic acid (-SO2H); alternate"
FT /evidence="ECO:0000269|PubMed:16894167,
FT ECO:0000269|PubMed:22515803"
FT VAR_SEQ 1
FT /note="M -> MVFFGFPQISRHFSKFTKM (in isoform 2)"
FT /id="VSP_058800"
FT MUTAGEN 45
FT /note="C->A,D: Lack of oxidation modification."
FT /evidence="ECO:0000269|PubMed:16894167"
FT MUTAGEN 104
FT /note="C->A,D: Lack of oxidation modification; results in
FT increased sensitivity to oxidative stress."
FT /evidence="ECO:0000269|PubMed:16894167"
FT STRAND 4..9
FT /evidence="ECO:0007829|PDB:4E08"
FT HELIX 15..27
FT /evidence="ECO:0007829|PDB:4E08"
FT STRAND 31..41
FT /evidence="ECO:0007829|PDB:4E08"
FT STRAND 50..52
FT /evidence="ECO:0007829|PDB:4E08"
FT STRAND 54..56
FT /evidence="ECO:0007829|PDB:4E08"
FT HELIX 58..60
FT /evidence="ECO:0007829|PDB:4E08"
FT STRAND 66..70
FT /evidence="ECO:0007829|PDB:4E08"
FT HELIX 74..82
FT /evidence="ECO:0007829|PDB:4E08"
FT HELIX 84..95
FT /evidence="ECO:0007829|PDB:4E08"
FT STRAND 99..103
FT /evidence="ECO:0007829|PDB:4E08"
FT TURN 104..106
FT /evidence="ECO:0007829|PDB:4E08"
FT HELIX 107..112
FT /evidence="ECO:0007829|PDB:4E08"
FT HELIX 125..130
FT /evidence="ECO:0007829|PDB:4E08"
FT STRAND 131..137
FT /evidence="ECO:0007829|PDB:4E08"
FT STRAND 142..146
FT /evidence="ECO:0007829|PDB:4E08"
FT STRAND 149..152
FT /evidence="ECO:0007829|PDB:4E08"
FT HELIX 155..157
FT /evidence="ECO:0007829|PDB:4E08"
FT HELIX 158..170
FT /evidence="ECO:0007829|PDB:4E08"
FT HELIX 172..182
FT /evidence="ECO:0007829|PDB:4E08"
SQ SEQUENCE 187 AA; 19250 MW; 224C8F694844A432 CRC64;
MSKSALVILA PGAEEMEFII AADVLRRAGI KVTVAGLNGG EAVKCSRDVQ ILPDTSLAQV
ASDKFDVVVL PGGLGGSNAM GESSLVGDLL RSQESGGGLI AAICAAPTVL AKHGVASGKS
LTSYPSMKPQ LVNNYSYVDD KTVVKDGNLI TSRGPGTAYE FALKIAEELA GKEKVQEVAK
GLLVAYN
