MOC2A_HUMAN
ID MOC2A_HUMAN Reviewed; 88 AA.
AC O96033;
DT 11-FEB-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 160.
DE RecName: Full=Molybdopterin synthase sulfur carrier subunit {ECO:0000255|HAMAP-Rule:MF_03051};
DE AltName: Full=MOCO1-A;
DE AltName: Full=Molybdenum cofactor synthesis protein 2 small subunit {ECO:0000255|HAMAP-Rule:MF_03051};
DE AltName: Full=Molybdenum cofactor synthesis protein 2A {ECO:0000255|HAMAP-Rule:MF_03051};
DE Short=MOCS2A {ECO:0000255|HAMAP-Rule:MF_03051};
DE AltName: Full=Molybdopterin-synthase small subunit;
DE AltName: Full=Sulfur carrier protein MOCS2A {ECO:0000255|HAMAP-Rule:MF_03051};
GN Name=MOCS2 {ECO:0000255|HAMAP-Rule:MF_03051}; Synonyms=MOCO1;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION OF BICISTRONIC GENE, AND TISSUE
RP SPECIFICITY.
RC TISSUE=Liver;
RX PubMed=10053003; DOI=10.1086/302295;
RA Stallmeyer B., Drugeon G., Reiss J., Haenni A.L., Mendel R.R.;
RT "Human molybdopterin synthase gene: identification of a bicistronic
RT transcript with overlapping reading frames.";
RL Am. J. Hum. Genet. 64:698-705(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=9889283; DOI=10.1093/nar/27.3.854;
RA Sloan J., Kinghorn J.R., Unkles S.E.;
RT "The two subunits of human molybdopterin synthase: evidence for a
RT bicistronic messenger RNA with overlapping reading frames.";
RL Nucleic Acids Res. 27:854-858(1999).
RN [3]
RP FUNCTION, SUBUNIT, THIOCARBOXYLATION AT GLY-88, AND CHARACTERIZATION OF
RP VARIANT MOCODB PHE-7.
RX PubMed=12732628; DOI=10.1074/jbc.m303092200;
RA Leimkuehler S., Freuer A., Araujo J.A., Rajagopalan K.V., Mendel R.R.;
RT "Mechanistic studies of human molybdopterin synthase reaction and
RT characterization of mutants identified in group B patients of molybdenum
RT cofactor deficiency.";
RL J. Biol. Chem. 278:26127-26134(2003).
RN [4]
RP SUBCELLULAR LOCATION, AMPYLATION AT GLY-88, AND THIOCARBOXYLATION AT
RP GLY-88.
RX PubMed=15073332; DOI=10.1073/pnas.0308191101;
RA Matthies A., Rajagopalan K.V., Mendel R.R., Leimkuehler S.;
RT "Evidence for the physiological role of a rhodanese-like protein for the
RT biosynthesis of the molybdenum cofactor in humans.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:5946-5951(2004).
RN [5]
RP THIOCARBOXYLATION AT GLY-88.
RX PubMed=15910006; DOI=10.1021/bi0503448;
RA Matthies A., Nimtz M., Leimkuehler S.;
RT "Molybdenum cofactor biosynthesis in humans: identification of a persulfide
RT group in the rhodanese-like domain of MOCS3 by mass spectrometry.";
RL Biochemistry 44:7912-7920(2005).
RN [6]
RP THIOCARBOXYLATION AT GLY-88.
RX PubMed=17459099; DOI=10.1111/j.1742-4658.2007.05811.x;
RA Krepinsky K., Leimkuehler S.;
RT "Site-directed mutagenesis of the active site loop of the rhodanese-like
RT domain of the human molybdopterin synthase sulfurase MOCS3. Major
RT differences in substrate specificity between eukaryotic and bacterial
RT homologs.";
RL FEBS J. 274:2778-2787(2007).
RN [7]
RP THIOCARBOXYLATION AT GLY-88.
RX PubMed=18491921; DOI=10.1021/bi800477u;
RA Schmitz J., Chowdhury M.M., Haenzelmann P., Nimtz M., Lee E.Y.,
RA Schindelin H., Leimkuehler S.;
RT "The sulfurtransferase activity of Uba4 presents a link between ubiquitin-
RT like protein conjugation and activation of sulfur carrier proteins.";
RL Biochemistry 47:6479-6489(2008).
RN [8]
RP INVOLVEMENT IN MOCODB.
RX PubMed=10053004; DOI=10.1086/302296;
RA Reiss J., Dorche C., Stallmeyer B., Mendel R.R., Cohen N., Zabot M.-T.;
RT "Human molybdopterin synthase gene: genomic structure and mutations in
RT molybdenum cofactor deficiency type B.";
RL Am. J. Hum. Genet. 64:706-711(1999).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA Ye M., Zou H.;
RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT phosphoproteome.";
RL J. Proteomics 96:253-262(2014).
RN [11]
RP VARIANT MOCODB PHE-7.
RX PubMed=11746050;
RX DOI=10.1002/1096-8628(20011122)104:2<169::aid-ajmg1603>3.0.co;2-8;
RA Johnson J.L., Coyne K.E., Rajagopalan K.V., Van Hove J.L.K., Mackay M.,
RA Pitt J., Boneh A.;
RT "Molybdopterin synthase mutations in a mild case of molybdenum cofactor
RT deficiency.";
RL Am. J. Med. Genet. 104:169-173(2001).
RN [12]
RP INVOLVEMENT IN MOCODB.
RX PubMed=16021469; DOI=10.1007/s00439-005-1341-9;
RA Leimkuehler S., Charcosset M., Latour P., Dorche C., Kleppe S., Scaglia F.,
RA Szymczak I., Schupp P., Hahnewald R., Reiss J.;
RT "Ten novel mutations in the molybdenum cofactor genes MOCS1 and MOCS2 and
RT in vitro characterization of a MOCS2 mutation that abolishes the binding
RT ability of molybdopterin synthase.";
RL Hum. Genet. 117:565-570(2005).
RN [13]
RP INVOLVEMENT IN MOCODB.
RX PubMed=16737835; DOI=10.1016/j.ymgme.2006.04.008;
RA Hahnewald R., Leimkuehler S., Vilaseca A., Acquaviva-Bourdain C., Lenz U.,
RA Reiss J.;
RT "A novel MOCS2 mutation reveals coordinated expression of the small and
RT large subunit of molybdopterin synthase.";
RL Mol. Genet. Metab. 89:210-213(2006).
CC -!- FUNCTION: Acts as a sulfur carrier required for molybdopterin
CC biosynthesis. Component of the molybdopterin synthase complex that
CC catalyzes the conversion of precursor Z into molybdopterin by mediating
CC the incorporation of 2 sulfur atoms into precursor Z to generate a
CC dithiolene group. In the complex, serves as sulfur donor by being
CC thiocarboxylated (-COSH) at its C-terminus by MOCS3. After interaction
CC with MOCS2B, the sulfur is then transferred to precursor Z to form
CC molybdopterin. {ECO:0000255|HAMAP-Rule:MF_03051,
CC ECO:0000269|PubMed:12732628}.
CC -!- PATHWAY: Cofactor biosynthesis; molybdopterin biosynthesis.
CC {ECO:0000255|HAMAP-Rule:MF_03051}.
CC -!- SUBUNIT: Heterotetramer; composed of 2 small (MOCS2A) and 2 large
CC (MOCS2B) subunits. {ECO:0000255|HAMAP-Rule:MF_03051}.
CC -!- INTERACTION:
CC O96033; O96007: MOCS2; NbExp=2; IntAct=EBI-9056334, EBI-723640;
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000255|HAMAP-
CC Rule:MF_03051, ECO:0000269|PubMed:15073332}.
CC -!- TISSUE SPECIFICITY: Widely expressed. Highest levels are found in heart
CC and skeletal muscle. Lower levels are present in brain, kidney and
CC pancreas. Very low levels are found in lung and peripheral blood
CC leukocytes. {ECO:0000269|PubMed:10053003, ECO:0000269|PubMed:9889283}.
CC -!- PTM: C-terminal thiocarboxylation occurs in 2 steps, it is first acyl-
CC adenylated (-COAMP) via the hesA/moeB/thiF part of MOCS3, then
CC thiocarboxylated (-COSH) via the rhodanese domain of MOCS3.
CC {ECO:0000255|HAMAP-Rule:MF_03051, ECO:0000269|PubMed:12732628,
CC ECO:0000269|PubMed:15073332, ECO:0000269|PubMed:15910006,
CC ECO:0000269|PubMed:17459099, ECO:0000269|PubMed:18491921}.
CC -!- DISEASE: Molybdenum cofactor deficiency, complementation group B
CC (MOCODB) [MIM:252160]: An autosomal recessive metabolic disorder
CC characterized by neonatal onset of intractable seizures, opisthotonus,
CC and facial dysmorphism associated with hypouricemia and elevated
CC urinary sulfite levels. Affected individuals show severe neurologic
CC damage and often die in early childhood. {ECO:0000269|PubMed:10053004,
CC ECO:0000269|PubMed:11746050, ECO:0000269|PubMed:12732628,
CC ECO:0000269|PubMed:16021469, ECO:0000269|PubMed:16737835}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- MISCELLANEOUS: This protein is produced by a bicistronic gene which
CC also produces the large subunit (MOCS2B) from an overlapping reading
CC frame. Expression of these 2 proteins are related since a mutation that
CC removes the start codon of the small subunit (MOCS2A) also impairs
CC expression of the large subunit (MOCS2B).
CC -!- SIMILARITY: Belongs to the MoaD family. MOCS2A subfamily.
CC {ECO:0000255|HAMAP-Rule:MF_03051}.
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DR EMBL; AF091871; AAD14598.1; -; mRNA.
DR EMBL; AF117815; AAD13296.1; -; mRNA.
DR CCDS; CCDS47205.1; -.
DR PIR; A59370; A59370.
DR RefSeq; NP_789776.1; NM_176806.3.
DR PDB; 5MPO; X-ray; 2.43 A; A/B=7-88.
DR PDBsum; 5MPO; -.
DR AlphaFoldDB; O96033; -.
DR SMR; O96033; -.
DR BioGRID; 110481; 15.
DR ComplexPortal; CPX-6341; Molybdopterin synthase complex.
DR CORUM; O96033; -.
DR IntAct; O96033; 3.
DR MINT; O96033; -.
DR iPTMnet; O96033; -.
DR BioMuta; MOCS2; -.
DR EPD; O96033; -.
DR jPOST; O96033; -.
DR MassIVE; O96033; -.
DR MaxQB; O96033; -.
DR PeptideAtlas; O96033; -.
DR PRIDE; O96033; -.
DR ProteomicsDB; 51223; -.
DR Antibodypedia; 23330; 160 antibodies from 23 providers.
DR DNASU; 4338; -.
DR Ensembl; ENST00000361377.8; ENSP00000355160.4; ENSG00000164172.20.
DR Ensembl; ENST00000450852.8; ENSP00000411022.3; ENSG00000164172.20.
DR Ensembl; ENST00000508922.5; ENSP00000426274.1; ENSG00000164172.20.
DR Ensembl; ENST00000510818.6; ENSP00000424267.2; ENSG00000164172.20.
DR Ensembl; ENST00000582677.5; ENSP00000462870.1; ENSG00000164172.20.
DR Ensembl; ENST00000584946.5; ENSP00000464663.1; ENSG00000164172.20.
DR GeneID; 4338; -.
DR UCSC; uc011cqf.4; human.
DR CTD; 4338; -.
DR DisGeNET; 4338; -.
DR GeneCards; MOCS2; -.
DR GeneReviews; MOCS2; -.
DR HGNC; HGNC:7193; MOCS2.
DR HPA; ENSG00000164172; Low tissue specificity.
DR MalaCards; MOCS2; -.
DR MIM; 252160; phenotype.
DR MIM; 603708; gene.
DR neXtProt; NX_O96033; -.
DR OpenTargets; ENSG00000164172; -.
DR PharmGKB; PA30903; -.
DR VEuPathDB; HostDB:ENSG00000164172; -.
DR GeneTree; ENSGT00510000047669; -.
DR BioCyc; MetaCyc:MON-16667; -.
DR PathwayCommons; O96033; -.
DR Reactome; R-HSA-947581; Molybdenum cofactor biosynthesis.
DR SignaLink; O96033; -.
DR UniPathway; UPA00344; -.
DR BioGRID-ORCS; 4338; 20 hits in 1078 CRISPR screens.
DR ChiTaRS; MOCS2; human.
DR GenomeRNAi; 4338; -.
DR Pharos; O96033; Tbio.
DR Proteomes; UP000005640; Chromosome 5.
DR Bgee; ENSG00000164172; Expressed in anterior cingulate cortex and 199 other tissues.
DR ExpressionAtlas; O96033; baseline and differential.
DR Genevisible; O96033; HS.
DR GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR GO; GO:0019008; C:molybdopterin synthase complex; IPI:UniProtKB.
DR GO; GO:0030366; F:molybdopterin synthase activity; IEA:UniProtKB-UniRule.
DR GO; GO:0000166; F:nucleotide binding; IEA:UniProtKB-KW.
DR GO; GO:0006777; P:Mo-molybdopterin cofactor biosynthetic process; IDA:UniProtKB.
DR Gene3D; 3.10.20.30; -; 1.
DR HAMAP; MF_03051; MOCS2A; 1.
DR InterPro; IPR012675; Beta-grasp_dom_sf.
DR InterPro; IPR044672; MOCS2A.
DR InterPro; IPR028887; MOCS2A_euk.
DR InterPro; IPR016155; Mopterin_synth/thiamin_S_b.
DR InterPro; IPR003749; ThiS/MoaD-like.
DR PANTHER; PTHR33359; PTHR33359; 1.
DR Pfam; PF02597; ThiS; 1.
DR SUPFAM; SSF54285; SSF54285; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Cytoplasm; Disease variant; Molybdenum cofactor biosynthesis;
KW Nucleotide-binding; Phosphoprotein; Reference proteome.
FT CHAIN 1..88
FT /note="Molybdopterin synthase sulfur carrier subunit"
FT /id="PRO_0000209134"
FT MOD_RES 88
FT /note="1-thioglycine; alternate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03051,
FT ECO:0000269|PubMed:12732628, ECO:0000269|PubMed:15073332,
FT ECO:0000269|PubMed:15910006, ECO:0000269|PubMed:17459099,
FT ECO:0000269|PubMed:18491921"
FT MOD_RES 88
FT /note="Glycyl adenylate; alternate"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_03051,
FT ECO:0000269|PubMed:15073332"
FT VARIANT 7
FT /note="V -> F (in MOCODB; in a patient with mild form of
FT the disease; impairs interaction with MOCS2B;
FT dbSNP:rs121908608)"
FT /evidence="ECO:0000269|PubMed:11746050,
FT ECO:0000269|PubMed:12732628"
FT /id="VAR_054854"
FT VARIANT 51
FT /note="V -> A (in dbSNP:rs2233210)"
FT /id="VAR_050090"
FT STRAND 7..11
FT /evidence="ECO:0007829|PDB:5MPO"
FT HELIX 14..19
FT /evidence="ECO:0007829|PDB:5MPO"
FT STRAND 22..27
FT /evidence="ECO:0007829|PDB:5MPO"
FT STRAND 30..33
FT /evidence="ECO:0007829|PDB:5MPO"
FT HELIX 34..44
FT /evidence="ECO:0007829|PDB:5MPO"
FT HELIX 46..54
FT /evidence="ECO:0007829|PDB:5MPO"
FT STRAND 56..59
FT /evidence="ECO:0007829|PDB:5MPO"
FT STRAND 62..64
FT /evidence="ECO:0007829|PDB:5MPO"
FT STRAND 66..68
FT /evidence="ECO:0007829|PDB:5MPO"
FT STRAND 70..72
FT /evidence="ECO:0007829|PDB:5MPO"
FT STRAND 78..82
FT /evidence="ECO:0007829|PDB:5MPO"
SQ SEQUENCE 88 AA; 9755 MW; BD08B374B615E7BE CRC64;
MVPLCQVEVL YFAKSAEITG VRSETISVPQ EIKALQLWKE IETRHPGLAD VRNQIIFAVR
QEYVELGDQL LVLQPGDEIA VIPPISGG
