MOCS2

Molybdenum cofactor synthesis protein 2A and molybdenum cofactor synthesis protein 2B are a pair of proteins that in humans are encoded from the same MOCS2 gene.[5][6][7] These two proteins dimerize to form molybdopterin synthase.

MOCS2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4AP8
Identifiers
Aliases	MOCS2, MCBPE, MOCO1, MOCODB, MPTS, molybdenum cofactor synthesis 2
External IDs	OMIM: 603708 MGI: 1336894 HomoloGene: 32193 GeneCards: MOCS2
Gene location (Human) Chr. Chromosome 5 (human)[1] Band 5q11.2 Start 53,095,679 bp[1] End 53,110,063 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13|13 D2.2 Start 114,818,236 bp[2] End 114,832,275 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • transferase activity • molybdopterin synthase activity • nucleotide binding Cellular component • molybdopterin synthase complex • cytosol • cell nucleus • cytoplasm • nuclear speck Biological process • Mo-molybdopterin cofactor biosynthetic process • molybdopterin cofactor biosynthetic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	4338	17434
Ensembl	ENSG00000164172	ENSMUSG00000015536
UniProt	O96007 O96033	Q9Z223 Q9Z224
RefSeq (mRNA)	NM_176806 NM_004531	NM_001113374 NM_001113375 NM_013826
RefSeq (protein)	NP_004522 NP_789776 NP_789776.1	NP_001106845 NP_001106846 NP_038854
Location (UCSC)	Chr 5: 53.1 – 53.11 Mb	Chr 13: 114.82 – 114.83 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Function

Eukaryotic molybdoenzymes use a unique molybdenum cofactor (MoCo) consisting of a pterin and the catalytically active metal molybdenum. MoCo is synthesized from cyclic pyranopterin monophosphate (precursor Z) by the heterodimeric enzyme molybdopterin synthase.[7]

Gene

The large and small subunits of molybdopterin synthase are both encoded from the MOCS2 gene by overlapping open reading frames. The proteins were initially thought to be encoded from a bicistronic transcript. They are now thought to be encoded from monocistronic transcripts. Alternatively spliced transcripts have been found for this locus that encode the large and small subunits.[7]

The MOCS2 gene contains 7 exons. Exons 1 to 3 encode MOCS2A (the small subunit), and exons 3 to 7 encode MOCS2B (large subunit).[5]

Genetic disease

Defects in both copies of MOCS2 cause the molybdenum cofactor deficiency disease in babies.[8]

Protein structure

MOCS2A and MOCS2B subunits form dimers in solution. These dimers in turn dimerize to form the tetrameric molybdopterin synthase complex.[9]

References

1. GRCh38: Ensembl release 89: ENSG00000164172 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000015536 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Reiss J, Dorche C, Stallmeyer B, Mendel RR, Cohen N, Zabot MT (March 1999). "Human molybdopterin synthase gene: genomic structure and mutations in molybdenum cofactor deficiency type B". American Journal of Human Genetics. 64 (3): 706–11. doi:10.1086/302296. PMC 1377787. PMID 10053004.
6. Sloan J, Kinghorn JR, Unkles SE (February 1999). "The two subunits of human molybdopterin synthase: evidence for a bicistronic messenger RNA with overlapping reading frames". Nucleic Acids Research. 27 (3): 854–8. doi:10.1093/nar/27.3.854. PMC 148257. PMID 9889283.
7. EntrezGene 4338: MOCS2 molybdenum cofactor synthesis 2
8. Ichida K, Aydin HI, Hosoyamada M, et al. (2006). "A Turkish case with molybdenum cofactor deficiency". Nucleosides, Nucleotides & Nucleic Acids. 25 (9–11): 1087–91. doi:10.1080/15257770600894022. PMID 17065069. S2CID 40601679.
9. Leimkuhler S, Freuer A, Araujo JA, Rajagopalan KV, Mendel RR (July 2003). "Mechanistic studies of human molybdopterin synthase reaction and characterization of mutants identified in group B patients of molybdenum cofactor deficiency". The Journal of Biological Chemistry. 278 (28): 26127–34. doi:10.1074/jbc.M303092200. PMID 12732628.

Further reading

• Reiss J, Johnson JL (June 2003). "Mutations in the molybdenum cofactor biosynthetic genes MOCS1, MOCS2, and GEPH". Human Mutation. 21 (6): 569–76. doi:10.1002/humu.10223. PMID 12754701. S2CID 41013043.
• Krawczak M, Reiss J, Cooper DN (1992). "The mutational spectrum of single base-pair substitutions in mRNA splice junctions of human genes: causes and consequences". Human Genetics. 90 (1–2): 41–54. doi:10.1007/bf00210743. PMID 1427786. S2CID 12544333.
• Reiss J, Cohen N, Dorche C, et al. (September 1998). "Mutations in a polycistronic nuclear gene associated with molybdenum cofactor deficiency". Nature Genetics. 20 (1): 51–3. doi:10.1038/1706. PMID 9731530. S2CID 23833158.
• Feng G, Tintrup H, Kirsch J, et al. (November 1998). "Dual requirement for gephyrin in glycine receptor clustering and molybdoenzyme activity". Science. 282 (5392): 1321–4. doi:10.1126/science.282.5392.1321. PMID 9812897.
• Stallmeyer B, Drugeon G, Reiss J, Haenni AL, Mendel RR (March 1999). "Human molybdopterin synthase gene: identification of a bicistronic transcript with overlapping reading frames". American Journal of Human Genetics. 64 (3): 698–705. doi:10.1086/302295. PMC 1377786. PMID 10053003.
• Johnson JL, Coyne KE, Rajagopalan KV, et al. (November 2001). "Molybdopterin synthase mutations in a mild case of molybdenum cofactor deficiency". American Journal of Medical Genetics. 104 (2): 169–73. doi:10.1002/1096-8628(20011122)104:2<169::AID-AJMG1603>3.0.CO;2-8. PMID 11746050.
• Strausberg RL, Feingold EA, Grouse LH, et al. (December 2002). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proceedings of the National Academy of Sciences of the United States of America. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Matthies A, Rajagopalan KV, Mendel RR, Leimkühler S (April 2004). "Evidence for the physiological role of a rhodanese-like protein for the biosynthesis of the molybdenum cofactor in humans". Proceedings of the National Academy of Sciences of the United States of America. 101 (16): 5946–51. doi:10.1073/pnas.0308191101. PMC 395903. PMID 15073332.
• Gerhard DS, Wagner L, Feingold EA, et al. (October 2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Research. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Leimkühler S, Charcosset M, Latour P, et al. (October 2005). "Ten novel mutations in the molybdenum cofactor genes MOCS1 and MOCS2 and in vitro characterization of a MOCS2 mutation that abolishes the binding ability of molybdopterin synthase". Human Genetics. 117 (6): 565–70. doi:10.1007/s00439-005-1341-9. PMID 16021469. S2CID 1267356.
• Hahnewald R, Leimkühler S, Vilaseca A, Acquaviva-Bourdain C, Lenz U, Reiss J (November 2006). "A novel MOCS2 mutation reveals coordinated expression of the small and large subunit of molybdopterin synthase". Molecular Genetics and Metabolism. 89 (3): 210–3. doi:10.1016/j.ymgme.2006.04.008. PMID 16737835.
• Beausoleil SA, Villén J, Gerber SA, Rush J, Gygi SP (October 2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nature Biotechnology. 24 (10): 1285–92. doi:10.1038/nbt1240. PMID 16964243. S2CID 14294292.
• Per H, Gümüş H, Ichida K, Cağlayan O, Kumandaş S (July 2007). "Molybdenum cofactor deficiency: clinical features in a Turkish patient". Brain & Development. 29 (6): 365–8. doi:10.1016/j.braindev.2006.10.007. PMID 17158010. S2CID 46531501.