MOCS3_DROME
ID MOCS3_DROME Reviewed; 453 AA.
AC Q9VLJ8; Q8T486;
DT 14-APR-2009, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 166.
DE RecName: Full=Adenylyltransferase and sulfurtransferase MOCS3 {ECO:0000255|HAMAP-Rule:MF_03049};
DE AltName: Full=Molybdenum cofactor synthesis protein 3 {ECO:0000255|HAMAP-Rule:MF_03049};
DE AltName: Full=Ubiquitin activating enzyme 4 {ECO:0000303|PubMed:26715182, ECO:0000312|FlyBase:FBgn0032054};
DE Includes:
DE RecName: Full=Molybdopterin-synthase adenylyltransferase {ECO:0000255|HAMAP-Rule:MF_03049};
DE EC=2.7.7.80 {ECO:0000255|HAMAP-Rule:MF_03049};
DE AltName: Full=Adenylyltransferase MOCS3 {ECO:0000255|HAMAP-Rule:MF_03049};
DE AltName: Full=Sulfur carrier protein MOCS2A adenylyltransferase {ECO:0000255|HAMAP-Rule:MF_03049};
DE Includes:
DE RecName: Full=Molybdopterin-synthase sulfurtransferase {ECO:0000255|HAMAP-Rule:MF_03049};
DE EC=2.8.1.11 {ECO:0000255|HAMAP-Rule:MF_03049};
DE AltName: Full=Sulfur carrier protein MOCS2A sulfurtransferase {ECO:0000255|HAMAP-Rule:MF_03049};
DE AltName: Full=Sulfurtransferase MOCS3 {ECO:0000255|HAMAP-Rule:MF_03049};
GN Name=Uba4 {ECO:0000303|PubMed:26715182, ECO:0000312|FlyBase:FBgn0032054};
GN ORFNames=CG13090 {ECO:0000312|FlyBase:FBgn0032054};
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 [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=Testis;
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 [LARGE SCALE MRNA].
RC STRAIN=Berkeley;
RA Carlson J.W., Booth B., Frise E., Park S., Wan K.H., Yu C., Celniker S.E.;
RL Submitted (SEP-2008) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-62, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
RN [6]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26715182; DOI=10.1007/s00018-015-2121-x;
RA Khoshnood B., Dacklin I., Grabbe C.;
RT "Urm1: an essential regulator of JNK signaling and oxidative stress in
RT Drosophila melanogaster.";
RL Cell. Mol. Life Sci. 73:1939-1954(2016).
CC -!- FUNCTION: Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA
CC wobble positions of cytosolic tRNA(Lys), tRNA(Glu) and tRNA(Gln) (By
CC similarity). Also essential during biosynthesis of the molybdenum
CC cofactor (By similarity). Acts by mediating the C-terminal
CC thiocarboxylation of sulfur carriers URM1 and MOCS2A (PubMed:26715182).
CC Its N-terminus first activates URM1 and MOCS2A as acyl-adenylates (-
CC COAMP), then the persulfide sulfur on the catalytic cysteine is
CC transferred to URM1 and MOCS2A to form thiocarboxylation (-COSH) of
CC their C-terminus (By similarity). The reaction probably involves
CC hydrogen sulfide that is generated from the persulfide intermediate and
CC that acts as nucleophile towards URM1 and MOCS2A (By similarity).
CC Subsequently, a transient disulfide bond is formed (PubMed:26715182).
CC Does not use thiosulfate as sulfur donor; NFS1 probably acting as a
CC sulfur donor for thiocarboxylation reactions (By similarity).
CC {ECO:0000255|HAMAP-Rule:MF_03049, ECO:0000269|PubMed:26715182}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[molybdopterin-synthase sulfur-carrier protein]-C-terminal
CC Gly-Gly + ATP + H(+) = [molybdopterin-synthase sulfur-carrier
CC protein]-C-terminal Gly-Gly-AMP + diphosphate; Xref=Rhea:RHEA:43616,
CC Rhea:RHEA-COMP:12159, Rhea:RHEA-COMP:12202, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:90618,
CC ChEBI:CHEBI:90778; EC=2.7.7.80; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03049};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[molybdopterin-synthase sulfur-carrier protein]-C-terminal
CC Gly-Gly-AMP + AH2 + S-sulfanyl-L-cysteinyl-[cysteine desulfurase] =
CC [molybdopterin-synthase sulfur-carrier protein]-C-terminal Gly-NH-
CC CH2-C(O)SH + A + AMP + H(+) + L-cysteinyl-[cysteine desulfurase];
CC Xref=Rhea:RHEA:48612, Rhea:RHEA-COMP:12157, Rhea:RHEA-COMP:12158,
CC Rhea:RHEA-COMP:12159, Rhea:RHEA-COMP:12160, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17499, ChEBI:CHEBI:29950,
CC ChEBI:CHEBI:61963, ChEBI:CHEBI:90618, ChEBI:CHEBI:90619,
CC ChEBI:CHEBI:456215; EC=2.8.1.11; Evidence={ECO:0000255|HAMAP-
CC Rule:MF_03049};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000255|HAMAP-Rule:MF_03049};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000255|HAMAP-Rule:MF_03049};
CC -!- PATHWAY: tRNA modification; 5-methoxycarbonylmethyl-2-thiouridine-tRNA
CC biosynthesis. {ECO:0000255|HAMAP-Rule:MF_03049}.
CC -!- PATHWAY: Cofactor biosynthesis; molybdopterin biosynthesis.
CC {ECO:0000255|HAMAP-Rule:MF_03049}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03049}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in reduced levels
CC of urmylation and increased resistance to oxidative stress.
CC {ECO:0000269|PubMed:26715182}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the HesA/MoeB/ThiF
CC family. UBA4 subfamily. {ECO:0000255|HAMAP-Rule:MF_03049}.
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DR EMBL; AE014134; AAF52691.1; -; Genomic_DNA.
DR EMBL; AY089305; AAL90043.1; -; mRNA.
DR EMBL; BT044400; ACH92465.1; -; mRNA.
DR RefSeq; NP_001260255.1; NM_001273326.1.
DR RefSeq; NP_001260256.1; NM_001273327.1.
DR RefSeq; NP_609240.2; NM_135396.3.
DR AlphaFoldDB; Q9VLJ8; -.
DR SMR; Q9VLJ8; -.
DR BioGRID; 60307; 27.
DR IntAct; Q9VLJ8; 3.
DR STRING; 7227.FBpp0079295; -.
DR iPTMnet; Q9VLJ8; -.
DR PaxDb; Q9VLJ8; -.
DR DNASU; 34187; -.
DR EnsemblMetazoa; FBtr0079683; FBpp0079295; FBgn0032054.
DR EnsemblMetazoa; FBtr0333413; FBpp0305605; FBgn0032054.
DR EnsemblMetazoa; FBtr0333414; FBpp0305606; FBgn0032054.
DR GeneID; 34187; -.
DR KEGG; dme:Dmel_CG13090; -.
DR UCSC; CG13090-RA; d. melanogaster.
DR CTD; 34187; -.
DR FlyBase; FBgn0032054; Uba4.
DR VEuPathDB; VectorBase:FBgn0032054; -.
DR eggNOG; KOG2017; Eukaryota.
DR GeneTree; ENSGT00940000160847; -.
DR HOGENOM; CLU_013325_1_2_1; -.
DR InParanoid; Q9VLJ8; -.
DR OMA; GTIGAMQ; -.
DR OrthoDB; 1445129at2759; -.
DR PhylomeDB; Q9VLJ8; -.
DR Reactome; R-DME-947581; Molybdenum cofactor biosynthesis.
DR UniPathway; UPA00344; -.
DR UniPathway; UPA00988; -.
DR BioGRID-ORCS; 34187; 1 hit in 1 CRISPR screen.
DR GenomeRNAi; 34187; -.
DR PRO; PR:Q9VLJ8; -.
DR Proteomes; UP000000803; Chromosome 2L.
DR Bgee; FBgn0032054; Expressed in oocyte and 22 other tissues.
DR ExpressionAtlas; Q9VLJ8; baseline and differential.
DR Genevisible; Q9VLJ8; DM.
DR GO; GO:0005737; C:cytoplasm; IDA:FlyBase.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0019008; C:molybdopterin synthase complex; IDA:FlyBase.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0061605; F:molybdopterin-synthase adenylyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0061604; F:molybdopterin-synthase sulfurtransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0016779; F:nucleotidyltransferase activity; IBA:GO_Central.
DR GO; GO:0070733; F:protein adenylyltransferase activity; ISS:FlyBase.
DR GO; GO:0004792; F:thiosulfate sulfurtransferase activity; ISS:UniProtKB.
DR GO; GO:0042292; F:URM1 activating enzyme activity; IBA:GO_Central.
DR GO; GO:0006777; P:Mo-molybdopterin cofactor biosynthetic process; ISS:UniProtKB.
DR GO; GO:0032324; P:molybdopterin cofactor biosynthetic process; IMP:FlyBase.
DR GO; GO:0032447; P:protein urmylation; IMP:FlyBase.
DR GO; GO:0034227; P:tRNA thio-modification; ISS:FlyBase.
DR GO; GO:0002143; P:tRNA wobble position uridine thiolation; IBA:GO_Central.
DR Gene3D; 3.40.250.10; -; 1.
DR HAMAP; MF_03049; MOCS3_Uba4; 1.
DR InterPro; IPR028885; MOCS3/Uba4.
DR InterPro; IPR001763; Rhodanese-like_dom.
DR InterPro; IPR036873; Rhodanese-like_dom_sf.
DR InterPro; IPR045886; ThiF/MoeB/HesA.
DR InterPro; IPR000594; ThiF_NAD_FAD-bd.
DR InterPro; IPR035985; Ubiquitin-activating_enz.
DR PANTHER; PTHR10953; PTHR10953; 1.
DR Pfam; PF00581; Rhodanese; 1.
DR Pfam; PF00899; ThiF; 1.
DR SMART; SM00450; RHOD; 1.
DR SUPFAM; SSF69572; SSF69572; 1.
DR PROSITE; PS50206; RHODANESE_3; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cytoplasm; Metal-binding; Molybdenum cofactor biosynthesis;
KW Multifunctional enzyme; Nucleotide-binding; Phosphoprotein;
KW Reference proteome; Transferase; tRNA processing; Zinc.
FT CHAIN 1..453
FT /note="Adenylyltransferase and sulfurtransferase MOCS3"
FT /id="PRO_0000369204"
FT DOMAIN 355..451
FT /note="Rhodanese"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT ACT_SITE 248
FT /note="Glycyl thioester intermediate; for
FT adenylyltransferase activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT ACT_SITE 410
FT /note="Cysteine persulfide intermediate; for
FT sulfurtransferase activity"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT BINDING 101
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT BINDING 122
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT BINDING 129..133
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT BINDING 146
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT BINDING 190..191
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT BINDING 231
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT BINDING 234
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT BINDING 306
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT BINDING 309
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT MOD_RES 62
FT /note="Phosphothreonine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT CONFLICT 349
FT /note="D -> E (in Ref. 3; AAL90043)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 453 AA; 50239 MW; C6978AF12E546CAF CRC64;
MMESEVDSER TMLKREIAEL RAALNQKEQC LRELDSLFSF ATRPEQEVVG NDLESPDVAV
HTKLTNDDIA RYSRQLILPD FGVQGQLKLK NSSVLIVGLG GLGCPAAQYL AAAGCGHLGL
VDYDEVERSN FHRQILHSED RCGMSKAESA RIALLELNPH CEIQCHSRML YPHNAMHIIR
GYDVVLDCTD NVPTRYLLSD ACVMLSKPLV SGSALKMDGQ LTVYNYANGP CYRCIFPVPP
PPEAVTNCGD GGVLGAVTGT IGAMQALEAI KVIVGMGDVL AGRLLIFDGG SGVFRNIRIR
SKRPNCHMCS AQPLITELIN YEMFCGMHAT DKNNPMLLLS TDERLSVEDY QQKIQAQPHL
LIDVRPTAEF EICQLPEAVN VPLVEILDDS YLKRLGKQLE DKELPIVLVC RRGNDSQIAV
QHLRNRFPTH FVRDLIGGLH AWTNSVDPSF PIY
