ID   MOCS3_MOUSE             Reviewed;         460 AA.
AC   A2BDX3;
DT   03-APR-2007, integrated into UniProtKB/Swiss-Prot.
DT   20-FEB-2007, sequence version 1.
DT   27-MAR-2024, entry version 121.
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   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=Mocs3; Synonyms=Uba4;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=C57BL/6J;
RX   PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA   Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA   Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA   Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA   Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA   Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA   Eichler E.E., Ponting C.P.;
RT   "Lineage-specific biology revealed by a finished genome assembly of the
RT   mouse.";
RL   PLoS Biol. 7:E1000112-E1000112(2009).
RN   [2]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver, Spleen, and Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
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). Also
CC       essential during biosynthesis of the molybdenum cofactor. Acts by
CC       mediating the C-terminal thiocarboxylation of sulfur carriers URM1 and
CC       MOCS2A. Its N-terminus first activates URM1 and MOCS2A as acyl-
CC       adenylates (-COAMP), then the persulfide sulfur on the catalytic
CC       cysteine is transferred to URM1 and MOCS2A to form thiocarboxylation (-
CC       COSH) of their C-terminus. The reaction probably involves hydrogen
CC       sulfide that is generated from the persulfide intermediate and that
CC       acts as a nucleophile towards URM1 and MOCS2A. Subsequently, a
CC       transient disulfide bond is formed. Does not use thiosulfate as sulfur
CC       donor; NFS1 acting as a sulfur donor for thiocarboxylation reactions.
CC       {ECO:0000255|HAMAP-Rule:MF_03049}.
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; Evidence={ECO:0000255|HAMAP-
CC         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   -!- SUBUNIT: Interacts with NFS1.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_03049}.
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; BX005039; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   CCDS; CCDS50802.1; -.
DR   RefSeq; NP_001153802.1; NM_001160330.1.
DR   AlphaFoldDB; A2BDX3; -.
DR   SMR; A2BDX3; -.
DR   IntAct; A2BDX3; 1.
DR   STRING; 10090.ENSMUSP00000096670; -.
DR   iPTMnet; A2BDX3; -.
DR   PhosphoSitePlus; A2BDX3; -.
DR   SwissPalm; A2BDX3; -.
DR   EPD; A2BDX3; -.
DR   MaxQB; A2BDX3; -.
DR   PaxDb; 10090-ENSMUSP00000096670; -.
DR   PeptideAtlas; A2BDX3; -.
DR   ProteomicsDB; 290289; -.
DR   Pumba; A2BDX3; -.
DR   Antibodypedia; 28627; 214 antibodies from 24 providers.
DR   Ensembl; ENSMUST00000099071.5; ENSMUSP00000096670.4; ENSMUSG00000074576.5.
DR   GeneID; 69372; -.
DR   KEGG; mmu:69372; -.
DR   UCSC; uc012cjs.1; mouse.
DR   AGR; MGI:1916622; -.
DR   CTD; 27304; -.
DR   MGI; MGI:1916622; Mocs3.
DR   VEuPathDB; HostDB:ENSMUSG00000074576; -.
DR   eggNOG; KOG2017; Eukaryota.
DR   GeneTree; ENSGT00940000160847; -.
DR   HOGENOM; CLU_013325_1_2_1; -.
DR   InParanoid; A2BDX3; -.
DR   OMA; IPDVGMD; -.
DR   OrthoDB; 53913at2759; -.
DR   PhylomeDB; A2BDX3; -.
DR   TreeFam; TF106103; -.
DR   Reactome; R-MMU-947581; Molybdenum cofactor biosynthesis.
DR   UniPathway; UPA00344; -.
DR   UniPathway; UPA00988; -.
DR   BioGRID-ORCS; 69372; 26 hits in 77 CRISPR screens.
DR   ChiTaRS; Mocs3; mouse.
DR   PRO; PR:A2BDX3; -.
DR   Proteomes; UP000000589; Chromosome 2.
DR   RNAct; A2BDX3; Protein.
DR   Bgee; ENSMUSG00000074576; Expressed in seminiferous tubule of testis and 204 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR   GO; GO:0005829; C:cytosol; ISS:UniProtKB.
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; ISS:UniProtKB.
DR   GO; GO:0016779; F:nucleotidyltransferase activity; ISS:UniProtKB.
DR   GO; GO:0016783; F:sulfurtransferase activity; ISS:UniProtKB.
DR   GO; GO:0004792; F:thiosulfate sulfurtransferase activity; IBA:GO_Central.
DR   GO; GO:0042292; F:URM1 activating enzyme activity; ISS:UniProtKB.
DR   GO; GO:0006777; P:Mo-molybdopterin cofactor biosynthetic process; ISS:UniProtKB.
DR   GO; GO:0032324; P:molybdopterin cofactor biosynthetic process; ISO:MGI.
DR   GO; GO:0043545; P:molybdopterin cofactor metabolic process; ISO:MGI.
DR   GO; GO:0032447; P:protein urmylation; IBA:GO_Central.
DR   GO; GO:0034227; P:tRNA thio-modification; ISS:UniProtKB.
DR   GO; GO:0002143; P:tRNA wobble position uridine thiolation; IBA:GO_Central.
DR   GO; GO:0002098; P:tRNA wobble uridine modification; ISS:UniProtKB.
DR   CDD; cd01526; RHOD_ThiF; 1.
DR   CDD; cd00757; ThiF_MoeB_HesA_family; 1.
DR   Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR   Gene3D; 3.40.250.10; Rhodanese-like domain; 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:SF102; ADENYLYLTRANSFERASE AND SULFURTRANSFERASE MOCS3; 1.
DR   PANTHER; PTHR10953; UBIQUITIN-ACTIVATING ENZYME E1; 1.
DR   Pfam; PF00581; Rhodanese; 1.
DR   Pfam; PF00899; ThiF; 1.
DR   SMART; SM00450; RHOD; 1.
DR   SUPFAM; SSF69572; Activating enzymes of the ubiquitin-like proteins; 1.
DR   PROSITE; PS50206; RHODANESE_3; 1.
DR   Genevisible; A2BDX3; MM.
PE   1: Evidence at protein level;
KW   ATP-binding; Cytoplasm; Disulfide bond; Metal-binding;
KW   Molybdenum cofactor biosynthesis; Multifunctional enzyme;
KW   Nucleotide-binding; Reference proteome; Transferase; tRNA processing; Zinc.
FT   CHAIN           1..460
FT                   /note="Adenylyltransferase and sulfurtransferase MOCS3"
FT                   /id="PRO_0000281918"
FT   DOMAIN          347..458
FT                   /note="Rhodanese"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT   REGION          158..238
FT                   /note="Interaction with NFS1"
FT                   /evidence="ECO:0000250|UniProtKB:O95396"
FT   ACT_SITE        239
FT                   /note="Glycyl thioester intermediate; for
FT                   adenylyltransferase activity"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT   ACT_SITE        412
FT                   /note="Cysteine persulfide intermediate; for
FT                   sulfurtransferase activity"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT   BINDING         92
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT   BINDING         113
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT   BINDING         120..124
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT   BINDING         137
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT   BINDING         181..182
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT   BINDING         222
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT   BINDING         225
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT   BINDING         297
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT   BINDING         300
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
FT   MOD_RES         412
FT                   /note="Cysteine persulfide"
FT                   /evidence="ECO:0000250|UniProtKB:O95396"
FT   DISULFID        316..324
FT                   /evidence="ECO:0000255|HAMAP-Rule:MF_03049"
SQ   SEQUENCE   460 AA;  49375 MW;  7340FD4B2D9826F1 CRC64;
     MAAPEDVAAL QAEITRREEE LASLKRRLAA ALTAEPEPER PLRVPPPPLA PRAALSRDEI
     LRYSRQLLLP ELGVRGQLRL AAAAVLVVGC GGLGCPLAQY LAAAGVGRLG LVDHDVVETS
     NLARQVLHGE AQAGESKARS AAAALRRLNS AVECVAYPRA LAEDWALDLV RGYDVVADCC
     DNVPTRYLVN DACVLAGRPL VSASALRFEG QMTVYHHDGG PCYRCVFPRP PPPETVTNCA
     DGGVLGAVPG VLGCAQALEV LKIAAGLGSS YSGSMLLFDG LGGHFRRIRL RRRRPDCVVC
     GQQPTVTRLQ DYEAFCGSSA TDKCRALKLL CPEERISVTD YKRLLDSGAP HVLLDVRPQV
     EVDICRLPHS LHIPLSQLER RDADSLKLLG AALRKGKQES QEGVALPVYV ICKLGNDSQK
     AVKVLQSLTA VPELDSLTVQ DIVGGLMAWA AKIDGTFPQY
//