MOCS1_MOUSE
ID MOCS1_MOUSE Reviewed; 636 AA.
AC Q5RKZ7; B2RVW8; B7ZWI5; Q8R058; Q9JL32; Q9JL33;
DT 14-APR-2009, integrated into UniProtKB/Swiss-Prot.
DT 14-APR-2009, sequence version 2.
DT 03-AUG-2022, entry version 127.
DE RecName: Full=Molybdenum cofactor biosynthesis protein 1;
DE Includes:
DE RecName: Full=GTP 3',8-cyclase;
DE EC=4.1.99.22 {ECO:0000250|UniProtKB:P69848};
DE AltName: Full=Molybdenum cofactor biosynthesis protein A;
DE Includes:
DE RecName: Full=Cyclic pyranopterin monophosphate synthase;
DE EC=4.6.1.17 {ECO:0000250|UniProtKB:Q9NZB8};
DE AltName: Full=Molybdenum cofactor biosynthesis protein C;
GN Name=Mocs1;
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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 99-636 (ISOFORM MOCS1A), AND NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 366-636 (ISOFORM MOCS1B).
RC STRAIN=FVB/N; TISSUE=Brain, and Liver;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 250-636 (ISOFORM MOCS1A), AND NUCLEOTIDE
RP SEQUENCE [MRNA] OF 388-594 (ISOFORM MOCS1B).
RX PubMed=10917590; DOI=10.1017/s1355838200000182;
RA Gray T.A., Nicholls R.D.;
RT "Diverse splicing mechanisms fuse the evolutionarily conserved bicistronic
RT MOCS1A and MOCS1B open reading frames.";
RL RNA 6:928-936(2000).
RN [4]
RP DISRUPTION PHENOTYPE.
RX PubMed=12471057; DOI=10.1093/hmg/11.26.3309;
RA Lee H.-J., Adham I.M., Schwarz G., Kneussel M., Sass J.O., Engel W.,
RA Reiss J.;
RT "Molybdenum cofactor-deficient mice resemble the phenotype of human
RT patients.";
RL Hum. Mol. Genet. 11:3309-3317(2002).
RN [5]
RP DISRUPTION PHENOTYPE.
RX PubMed=15862276; DOI=10.1016/j.ymgme.2005.01.008;
RA Reiss J., Bonin M., Schwegler H., Sass J.O., Garattini E., Wagner S.,
RA Lee H.-J., Engel W., Riess O., Schwarz G.;
RT "The pathogenesis of molybdenum cofactor deficiency, its delay by maternal
RT clearance, and its expression pattern in microarray analysis.";
RL Mol. Genet. Metab. 85:12-20(2005).
RN [6]
RP DISRUPTION PHENOTYPE.
RX PubMed=17236133; DOI=10.1086/511281;
RA Kuegler S., Hahnewald R., Garrido M., Reiss J.;
RT "Long-term rescue of a lethal inherited disease by adeno-associated virus-
RT mediated gene transfer in a mouse model of molybdenum-cofactor
RT deficiency.";
RL Am. J. Hum. Genet. 80:291-297(2007).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Heart, Kidney, 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).
RN [8]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-528, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=23576753; DOI=10.1073/pnas.1302961110;
RA Rardin M.J., Newman J.C., Held J.M., Cusack M.P., Sorensen D.J., Li B.,
RA Schilling B., Mooney S.D., Kahn C.R., Verdin E., Gibson B.W.;
RT "Label-free quantitative proteomics of the lysine acetylome in mitochondria
RT identifies substrates of SIRT3 in metabolic pathways.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:6601-6606(2013).
CC -!- FUNCTION: Isoform Mocs1a and isoform Mocs1b probably form a complex
CC that catalyzes the conversion of 5'-GTP to cyclic pyranopterin
CC monophosphate (cPMP). Mocs1a catalyzes the cyclization of GTP to (8S)-
CC 3',8-cyclo-7,8-dihydroguanosine 5'-triphosphate and Mocs1b catalyzes
CC the subsequent conversion of (8S)-3',8-cyclo-7,8-dihydroguanosine 5'-
CC triphosphate to cPMP. {ECO:0000250|UniProtKB:Q9NZB8}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=AH2 + GTP + S-adenosyl-L-methionine = (8S)-3',8-cyclo-7,8-
CC dihydroguanosine 5'-triphosphate + 5'-deoxyadenosine + A + H(+) + L-
CC methionine; Xref=Rhea:RHEA:49576, ChEBI:CHEBI:13193,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:17319, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:37565, ChEBI:CHEBI:57844, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:131766; EC=4.1.99.22;
CC Evidence={ECO:0000250|UniProtKB:P69848};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(8S)-3',8-cyclo-7,8-dihydroguanosine 5'-triphosphate = cyclic
CC pyranopterin phosphate + diphosphate; Xref=Rhea:RHEA:49580,
CC ChEBI:CHEBI:33019, ChEBI:CHEBI:59648, ChEBI:CHEBI:131766;
CC EC=4.6.1.17; Evidence={ECO:0000250|UniProtKB:Q9NZB8};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000250|UniProtKB:Q9NZB8};
CC Note=Binds 2 [4Fe-4S] clusters. Binds 1 [4Fe-4S] cluster coordinated
CC with 3 cysteines and an exchangeable S-adenosyl-L-methionine and 1
CC [4Fe-4S] cluster coordinated with 3 cysteines and the GTP-derived
CC substrate. {ECO:0000250|UniProtKB:Q9NZB8};
CC -!- PATHWAY: Cofactor biosynthesis; molybdopterin biosynthesis.
CC -!- SUBUNIT: Isoform Mocs1a and isoform Mocs1b probably form a
CC heterooligomer. {ECO:0000250|UniProtKB:Q9NZB8}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=Mocs1b;
CC IsoId=Q5RKZ7-1; Sequence=Displayed;
CC Name=Mocs1a;
CC IsoId=Q5RKZ7-2; Sequence=VSP_036850, VSP_036851;
CC Name=3;
CC IsoId=Q5RKZ7-3; Sequence=VSP_036849;
CC -!- DISRUPTION PHENOTYPE: Death between days 1 and 11 after birth, due to a
CC progressive neurological disorder caused by massive cell death. Death
CC is caused by the absence of molybdenum cofactor, resulting in elevated
CC sulfite and diminished sulfate levels throughout the organism. Mice do
CC not possess any sulfite oxidase or xanthine dehydrogenase activity. No
CC organ abnormalities are observed and the synaptic localization of
CC inhibitory receptors appears normal. Long-term rescue results have been
CC obtained in mice lacking Mocs1 thanks to an adeno-associated virus-
CC mediated gene transfer. {ECO:0000269|PubMed:12471057,
CC ECO:0000269|PubMed:15862276, ECO:0000269|PubMed:17236133}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the MoaC family.
CC {ECO:0000305}.
CC -!- SIMILARITY: In the N-terminal section; belongs to the radical SAM
CC superfamily. MoaA family. {ECO:0000305}.
CC -!- CAUTION: The C-terminus of Mocs1a was previously believed to be
CC thiocarboxylated, but it is now known not to be the case.
CC {ECO:0000250|UniProtKB:Q9NZB8}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI47413.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AC165258; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC027444; AAH27444.1; -; mRNA.
DR EMBL; BC049914; AAH49914.1; -; mRNA.
DR EMBL; BC147411; AAI47412.1; -; mRNA.
DR EMBL; BC147412; AAI47413.1; ALT_INIT; mRNA.
DR EMBL; BC172067; AAI72067.1; -; mRNA.
DR EMBL; AF214016; AAF67845.1; -; mRNA.
DR EMBL; AF214016; AAF67846.1; -; mRNA.
DR CCDS; CCDS50143.1; -. [Q5RKZ7-1]
DR CCDS; CCDS57100.1; -. [Q5RKZ7-2]
DR RefSeq; NP_064426.2; NM_020042.2. [Q5RKZ7-1]
DR RefSeq; NP_082740.1; NM_028464.1. [Q5RKZ7-2]
DR AlphaFoldDB; Q5RKZ7; -.
DR SMR; Q5RKZ7; -.
DR BioGRID; 208152; 2.
DR STRING; 10090.ENSMUSP00000133694; -.
DR iPTMnet; Q5RKZ7; -.
DR PhosphoSitePlus; Q5RKZ7; -.
DR EPD; Q5RKZ7; -.
DR jPOST; Q5RKZ7; -.
DR MaxQB; Q5RKZ7; -.
DR PaxDb; Q5RKZ7; -.
DR PeptideAtlas; Q5RKZ7; -.
DR PRIDE; Q5RKZ7; -.
DR ProteomicsDB; 290286; -. [Q5RKZ7-1]
DR ProteomicsDB; 290287; -. [Q5RKZ7-2]
DR ProteomicsDB; 290288; -. [Q5RKZ7-3]
DR Antibodypedia; 51647; 194 antibodies from 21 providers.
DR DNASU; 56738; -.
DR Ensembl; ENSMUST00000024797; ENSMUSP00000024797; ENSMUSG00000064120. [Q5RKZ7-2]
DR Ensembl; ENSMUST00000173033; ENSMUSP00000133694; ENSMUSG00000064120. [Q5RKZ7-1]
DR GeneID; 56738; -.
DR KEGG; mmu:56738; -.
DR UCSC; uc008cyg.2; mouse. [Q5RKZ7-1]
DR UCSC; uc008cyh.2; mouse. [Q5RKZ7-2]
DR CTD; 4337; -.
DR MGI; MGI:1928904; Mocs1.
DR VEuPathDB; HostDB:ENSMUSG00000064120; -.
DR eggNOG; KOG2876; Eukaryota.
DR GeneTree; ENSGT00390000016567; -.
DR HOGENOM; CLU_009273_0_0_1; -.
DR InParanoid; Q5RKZ7; -.
DR OMA; IRDAKPF; -.
DR OrthoDB; 721528at2759; -.
DR PhylomeDB; Q5RKZ7; -.
DR TreeFam; TF300424; -.
DR Reactome; R-MMU-947581; Molybdenum cofactor biosynthesis.
DR UniPathway; UPA00344; -.
DR BioGRID-ORCS; 56738; 2 hits in 73 CRISPR screens.
DR ChiTaRS; Mocs1; mouse.
DR PRO; PR:Q5RKZ7; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; Q5RKZ7; protein.
DR Bgee; ENSMUSG00000064120; Expressed in granulocyte and 102 other tissues.
DR ExpressionAtlas; Q5RKZ7; baseline and differential.
DR Genevisible; Q5RKZ7; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0019008; C:molybdopterin synthase complex; IEA:InterPro.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; ISO:MGI.
DR GO; GO:0061799; F:cyclic pyranopterin monophosphate synthase activity; IMP:MGI.
DR GO; GO:0061798; F:GTP 3',8'-cyclase activity; IMP:MGI.
DR GO; GO:0005525; F:GTP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006777; P:Mo-molybdopterin cofactor biosynthetic process; ISO:MGI.
DR GO; GO:0032324; P:molybdopterin cofactor biosynthetic process; IMP:MGI.
DR CDD; cd01420; MoaC_PE; 1.
DR Gene3D; 3.20.20.70; -; 1.
DR Gene3D; 3.30.70.640; -; 1.
DR HAMAP; MF_01225_B; MoaA_B; 1.
DR HAMAP; MF_01224_B; MoaC_B; 1.
DR InterPro; IPR013785; Aldolase_TIM.
DR InterPro; IPR006638; Elp3/MiaB/NifB.
DR InterPro; IPR023045; Mo_CF_biosynth-C.
DR InterPro; IPR013483; MoaA.
DR InterPro; IPR000385; MoaA_NifB_PqqE_Fe-S-bd_CS.
DR InterPro; IPR036522; MoaC_sf.
DR InterPro; IPR010505; Mob_synth_C.
DR InterPro; IPR002820; Mopterin_CF_biosynth-C_dom.
DR InterPro; IPR007197; rSAM.
DR Pfam; PF01967; MoaC; 1.
DR Pfam; PF06463; Mob_synth_C; 1.
DR Pfam; PF04055; Radical_SAM; 1.
DR SMART; SM00729; Elp3; 1.
DR SUPFAM; SSF55040; SSF55040; 1.
DR TIGRFAMs; TIGR02666; moaA; 1.
DR TIGRFAMs; TIGR00581; moaC; 1.
DR PROSITE; PS01305; MOAA_NIFB_PQQE; 1.
DR PROSITE; PS51918; RADICAL_SAM; 1.
PE 1: Evidence at protein level;
KW 4Fe-4S; Acetylation; Alternative splicing; GTP-binding; Iron; Iron-sulfur;
KW Lyase; Metal-binding; Molybdenum cofactor biosynthesis; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; S-adenosyl-L-methionine.
FT CHAIN 1..636
FT /note="Molybdenum cofactor biosynthesis protein 1"
FT /id="PRO_0000369400"
FT DOMAIN 64..279
FT /note="Radical SAM core"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01266"
FT REGION 1..383
FT /note="Molybdenum cofactor biosynthesis protein A"
FT REGION 19..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 414..636
FT /note="Molybdenum cofactor biosynthesis protein C"
FT REGION 444..484
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 606
FT /note="For molybdenum cofactor biosynthesis protein C
FT activity"
FT /evidence="ECO:0000255"
FT BINDING 73
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 80
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000250"
FT BINDING 84
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000250"
FT BINDING 86
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 87
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="1"
FT /ligand_note="4Fe-4S-S-AdoMet"
FT /evidence="ECO:0000250"
FT BINDING 123
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 127
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 154
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 178
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 215
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 249
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250"
FT BINDING 312
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /ligand_note="4Fe-4S-substrate"
FT /evidence="ECO:0000250"
FT BINDING 315
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /ligand_note="4Fe-4S-substrate"
FT /evidence="ECO:0000250"
FT BINDING 317..319
FT /ligand="GTP"
FT /ligand_id="ChEBI:CHEBI:37565"
FT /evidence="ECO:0000250"
FT BINDING 329
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /ligand_label="2"
FT /ligand_note="4Fe-4S-substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 64
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZB8"
FT MOD_RES 198
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9NZB8"
FT MOD_RES 528
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:23576753"
FT VAR_SEQ 1..387
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_036849"
FT VAR_SEQ 385
FT /note="V -> G (in isoform Mocs1a)"
FT /evidence="ECO:0000303|PubMed:10917590,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_036850"
FT VAR_SEQ 386..636
FT /note="Missing (in isoform Mocs1a)"
FT /evidence="ECO:0000303|PubMed:10917590,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_036851"
FT CONFLICT 267
FT /note="M -> V (in Ref. 3; AAF67845)"
FT /evidence="ECO:0000305"
FT CONFLICT 274
FT /note="R -> Q (in Ref. 2; AAH49914)"
FT /evidence="ECO:0000305"
FT CONFLICT 289
FT /note="A -> T (in Ref. 3; AAF67845)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 636 AA; 69859 MW; 9AEFB16970B3EE9F CRC64;
MAARPAFGIV RQLLRSNARG CSSGAPVTQP RPGEPSRPTR EGLSLRLQFL QEHAAPFSAF
LTDSFGRQHS YLRISLTEKC NLRCQYCMPE EGVPLTPKAD LLTTEEILTL ARLFVKEGVD
KIRLTGGEPL IRPDVVDIVA RLHGLEGLRT IGLTTNGINL ARLLPRLQQA GLNAVNISLD
TLVPAKFEFI VRRKGFHKVM EGIHKAIELG YKPVKVNCVV MRGLNEDELL DFVALTEGLP
LDVRFIEYMP FDGNKWNFKK MVSYKEMLDT IRQRWPGLEK LPEEDSSTAK AFKIPGFQGQ
ISFITSMSEH FCGTCNRLRI TADGNLKVCL FGNSEVSLRD HLRAGASEEE LLRIIGAAVG
RKKRQHAGMF NIAQMKNRPM ILIGVLLMLQ DSPPARWSNF SWDPLRVRNP SARQCLSDQM
ASLWKRHCIP KALPLSQQCL GSGSPQRHYS SYPDPDTHSK CLSTGSQAPD APSGPGPTSN
QLTHVDSAGR ASMVDVGGKP ETERVAVASA MVLLGPVAFK LVQQNQLKKG DALVVAQLAG
VQAAKLTSQL IPLCHHVALS HVQVHLELDS TRHAVLIQAS CRARGPTGVE MEALTSAAMA
ALTVYDMCKA VSRDIVVTEV KLISKTGGQR GDFHRA
