SEPIA_DROME
ID SEPIA_DROME Reviewed; 243 AA.
AC Q9VSL3; D1KS67; D1KS72;
DT 29-OCT-2014, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 183.
DE RecName: Full=Pyrimidodiazepine synthase {ECO:0000305};
DE EC=1.5.4.1 {ECO:0000269|PubMed:16712527};
DE AltName: Full=Protein sepia {ECO:0000303|PubMed:16712527};
GN Name=se {ECO:0000312|FlyBase:FBgn0086348};
GN ORFNames=CG6781 {ECO:0000312|FlyBase:FBgn0086348};
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 {ECO:0000312|EMBL:AAF50405.1};
RN [1]
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 [2]
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Head;
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 [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-200.
RX PubMed=19608790; DOI=10.1093/jhered/esp043;
RA Walters K.B., Grant P., Johnson D.L.;
RT "Evolution of the GST omega gene family in 12 Drosophila species.";
RL J. Hered. 100:742-753(2009).
RN [5]
RP FUNCTION.
RX PubMed=6438092; DOI=10.1016/s0021-9258(18)89865-9;
RA Wiederrecht G.J., Brown G.M.;
RT "Purification and properties of the enzymes from Drosophila melanogaster
RT that catalyze the conversion of dihydroneopterin triphosphate to the
RT pyrimidodiazepine precursor of the drosopterins.";
RL J. Biol. Chem. 259:14121-14127(1984).
RN [6]
RP FUNCTION, CATALYTIC ACTIVITY, DISRUPTION PHENOTYPE, SUBUNIT, AND
RP DEVELOPMENTAL STAGE.
RX PubMed=16712527; DOI=10.1042/bj20060424;
RA Kim J., Suh H., Kim S., Kim K., Ahn C., Yim J.;
RT "Identification and characteristics of the structural gene for the
RT Drosophila eye color mutant sepia, encoding PDA synthase, a member of the
RT omega class glutathione S-transferases.";
RL Biochem. J. 398:451-460(2006).
CC -!- FUNCTION: Mediates the conversion of 2-amino-4-oxo-6-pyruvoyl-5,6,7,8-
CC tetrahydropteridine (6-PTP; also named 6-pyruvoyltetrahydropterin) to
CC 2-amino-6-acetyl-3,7,8,9-tetrahydro-3H-pyrimido(4,5-b)[1,4]diazepin-4-
CC one (pyrimidodiazepine or PDA), a key intermediate in red eye pigment
CC drosopterin biosynthesis. {ECO:0000269|PubMed:16712527,
CC ECO:0000269|PubMed:6438092}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-amino-6-acetyl-3,7,8,9-tetrahydro-3H-pyrimido[4,5-
CC b][1,4]diazepin-4-one + glutathione disulfide + H2O = 6-pyruvoyl-
CC 5,6,7,8-tetrahydropterin + 2 glutathione; Xref=Rhea:RHEA:10720,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:27714, ChEBI:CHEBI:57925,
CC ChEBI:CHEBI:58297, ChEBI:CHEBI:136564; EC=1.5.4.1;
CC Evidence={ECO:0000269|PubMed:16712527};
CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:16712527}.
CC -!- DEVELOPMENTAL STAGE: Appears only at the late pupal stage; expressed at
CC high level. Also expressed in the early adult (0-2 days old) at lower
CC level. Expressed exclusively in the adult head.
CC {ECO:0000269|PubMed:16712527}.
CC -!- DISRUPTION PHENOTYPE: Sepia eye color, due to defects in 2-amino-6-
CC acetyl-3,7,8,9-tetrahydro-3H-pyrimido(4,5-b)[1,4]diazepin-4-one
CC (pyrimidodiazepine or PDA) synthesis, a key intermediate in red eye
CC pigment drosopterin biosynthesis. {ECO:0000269|PubMed:16712527}.
CC -!- SIMILARITY: Belongs to the GST superfamily. Omega family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=ACZ02425.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC Sequence=ACZ02430.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR EMBL; AE014296; AAF50405.1; -; Genomic_DNA.
DR EMBL; AY070667; AAL48138.1; -; mRNA.
DR EMBL; GQ351317; ACZ02425.1; ALT_SEQ; Genomic_DNA.
DR EMBL; GQ351318; ACZ02430.1; ALT_SEQ; Genomic_DNA.
DR RefSeq; NP_648235.1; NM_139978.4.
DR AlphaFoldDB; Q9VSL3; -.
DR SMR; Q9VSL3; -.
DR BioGRID; 64383; 1.
DR IntAct; Q9VSL3; 1.
DR STRING; 7227.FBpp0076349; -.
DR PaxDb; Q9VSL3; -.
DR PRIDE; Q9VSL3; -.
DR DNASU; 38973; -.
DR EnsemblMetazoa; FBtr0076623; FBpp0076349; FBgn0086348.
DR GeneID; 38973; -.
DR KEGG; dme:Dmel_CG6781; -.
DR UCSC; CG6781-RA; d. melanogaster.
DR CTD; 38973; -.
DR FlyBase; FBgn0086348; se.
DR VEuPathDB; VectorBase:FBgn0086348; -.
DR eggNOG; KOG0406; Eukaryota.
DR GeneTree; ENSGT00940000163896; -.
DR HOGENOM; CLU_011226_9_2_1; -.
DR InParanoid; Q9VSL3; -.
DR OMA; ADHYSHR; -.
DR OrthoDB; 1225872at2759; -.
DR PhylomeDB; Q9VSL3; -.
DR BioCyc; MetaCyc:MON-18458; -.
DR Reactome; R-DME-156590; Glutathione conjugation.
DR Reactome; R-DME-196836; Vitamin C (ascorbate) metabolism.
DR BioGRID-ORCS; 38973; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 38973; -.
DR PRO; PR:Q9VSL3; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0086348; Expressed in insect adult head and 8 other tissues.
DR Genevisible; Q9VSL3; DM.
DR GO; GO:0005737; C:cytoplasm; ISS:FlyBase.
DR GO; GO:0045174; F:glutathione dehydrogenase (ascorbate) activity; IDA:FlyBase.
DR GO; GO:0004364; F:glutathione transferase activity; IDA:FlyBase.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:FlyBase.
DR GO; GO:0004734; F:pyrimidodiazepine synthase activity; IDA:FlyBase.
DR GO; GO:0006726; P:eye pigment biosynthetic process; IGI:FlyBase.
DR GO; GO:0006749; P:glutathione metabolic process; IDA:FlyBase.
DR GO; GO:0006728; P:pteridine biosynthetic process; IDA:FlyBase.
DR InterPro; IPR010987; Glutathione-S-Trfase_C-like.
DR InterPro; IPR036282; Glutathione-S-Trfase_C_sf.
DR InterPro; IPR040079; Glutathione_S-Trfase.
DR InterPro; IPR004045; Glutathione_S-Trfase_N.
DR InterPro; IPR005442; GST_omega.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR Pfam; PF13417; GST_N_3; 1.
DR PRINTS; PR01625; GSTRNSFRASEO.
DR SFLD; SFLDS00019; Glutathione_Transferase_(cytos; 1.
DR SUPFAM; SSF47616; SSF47616; 1.
DR SUPFAM; SSF52833; SSF52833; 1.
DR PROSITE; PS50405; GST_CTER; 1.
DR PROSITE; PS50404; GST_NTER; 1.
PE 1: Evidence at protein level;
KW Oxidoreductase; Reference proteome.
FT CHAIN 1..243
FT /note="Pyrimidodiazepine synthase"
FT /id="PRO_0000430582"
FT DOMAIN 20..102
FT /note="GST N-terminal"
FT /evidence="ECO:0000255"
FT DOMAIN 107..230
FT /note="GST C-terminal"
FT /evidence="ECO:0000255"
FT ACT_SITE 30
FT /note="Nucleophile"
FT /evidence="ECO:0000250|UniProtKB:P78417"
FT BINDING 57
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000250|UniProtKB:P78417"
FT BINDING 70
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000250|UniProtKB:P78417"
FT BINDING 86..87
FT /ligand="glutathione"
FT /ligand_id="ChEBI:CHEBI:57925"
FT /evidence="ECO:0000250|UniProtKB:P78417"
SQ SEQUENCE 243 AA; 28413 MW; A6B651F36487A5AE CRC64;
MSNGRHLAKG SPMPDVPEDG ILRLYSMRFC PFAQRVHLVL DAKQIPYHSI YINLTDKPEW
LLEKNPQGKV PALEIVREPG PPVLTESLLI CEYLDEQYPL RPLYPRDPLK KVQDKLLIER
FRAVLGAFFK ASDGGDLEPF WSGLDIYERE LARRGTEFFG GEQTGILDYM IWPWCERLEL
LKLQRGEDYN YDQSRFPQLT LWLERMKRDP AVMAFYMEAE VQAEFLRTRS LGRPNYNLLV
KDA
