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Identification
HMDB Protein ID HMDBP02017
Secondary Accession Numbers
  • 7473
Name Adenylyltransferase and sulfurtransferase MOCS3
Synonyms
  1. Adenylyltransferase MOCS3
  2. MPT synthase sulfurylase
  3. Molybdenum cofactor synthesis protein 3
  4. Molybdopterin synthase sulfurylase
  5. Sulfur carrier protein MOCS2A adenylyltransferase
  6. Sulfur carrier protein MOCS2A sulfurtransferase
  7. Sulfurtransferase MOCS3
Gene Name MOCS3
Protein Type Enzyme
Biological Properties
General Function Involved in catalytic activity
Specific Function Plays a central role in 2-thiolation of mcm(5)S(2)U at tRNA wobble positions of tRNA(Lys), tRNA(Glu) and tRNA(Gln). Also essential during biosynthesis of the molybdenum cofactor. Acts by mediating the C-terminal thiocarboxylation of sulfur carriers URM1 and MOCS2A. Its N-terminus first activates URM1 and MOCS2A as acyl-adenylates (-COAMP), then the persulfide sulfur on the catalytic cysteine is transferred to URM1 and MOCS2A to form thiocarboxylation (-COSH) of their C-terminus. The reaction probably involves hydrogen sulfide that is generated from the persulfide intermediate and that acts as nucleophile towards URM1 and MOCS2A. Subsequently, a transient disulfide bond is formed. Does not use thiosulfate as sulfur donor; NFS1 probably acting as a sulfur donor for thiocarboxylation reactions.
Pathways
  • 5-methoxycarbonylmethyl-2-thiouridine-tRNA biosynthesis
  • molybdopterin biosynthesis
  • Sulfur relay system
Reactions
Adenosine triphosphate + [molybdopterin-synthase sulfur-carrier protein]-Gly-Gly → Pyrophosphate + [molybdopterin-synthase sulfur-carrier protein]-Gly-Gly-AMP details
[Molybdopterin-synthase sulfur-carrier protein]-Gly-Gly-AMP + [cysteine desulfurase]-S-sulfanyl-L-cysteine → Adenosine monophosphate + [molybdopterin-synthase sulfur-carrier protein]-Gly-NH-CH(2)-C(O)SH + cysteine desulfurase details
GO Classification
Biological Process
enzyme active site formation via L-cysteine persulfide
tRNA thio-modification
tRNA wobble uridine modification
water-soluble vitamin metabolic process
Mo-molybdopterin cofactor biosynthetic process
Cellular Component
cytosol
Function
binding
catalytic activity
Molecular Function
thiosulfate sulfurtransferase activity
nucleotidyltransferase activity
URM1 activating enzyme activity
metal ion binding
ATP binding
Process
metabolic process
Cellular Location
  1. Cytoplasm
  2. cytosol
Gene Properties
Chromosome Location 20
Locus 20q13.13
SNPs MOCS3
Gene Sequence
>1383 bp
ATGGCTTCCCGGGAGGAGGTACTCGCCTTACAAGCTGAAGTTGCCCAACGTGAGGAGGAA
TTGAATTCGCTGAAGCAGAAGCTGGCGTCGGCTCTTTTGGCTGAGCAGGAACCGCAGCCA
GAACGGCTGGTTCCGGTGTCGCCGCTGCCGCCGAAGGCCGCTCTGTCCCGAGATGAGATT
CTGCGCTATAGCCGGCAGCTAGTGCTGCCCGAGCTGGGCGTGCACGGACAGCTGCGCCTG
GGGACCGCGTGCGTGCTAATCGTGGGCTGCGGTGGGCTCGGCTGTCCACTAGCGCAGTAC
TTGGCAGCGGCCGGCGTGGGCCGCCTTGGCCTTGTGGACTATGACGTGGTAGAGATGAGC
AACCTGGCCCGCCAAGTGCTGCATGGCGAGGCACTGGCTGGCCAGGCCAAGGCCTTTTCG
GCCGCCGCCTCGCTGCGCCGCCTCAATTCGGCAGTGGAATGCGTGCCGTACACTCAGGCC
CTTACGCCAGCCACTGCCCTAGACCTGGTCCGCCGATATGATGTGGTGGCTGACTGCTCG
GACAACGTGCCCACTCGCTACCTGGTTAATGACGCATGTGTGCTGGCGGGTCGGCCCCTC
GTGTCTGCCAGTGCCTTGCGCTTCGAGGGCCAAATCACAGTCTACCATTATGACGGTGGC
CCTTGCTATCGCTGCATATTCCCCCAACCACCCCCAGCGGAGACAGTGACCAACTGCGCG
GACGGCGGGGTGCTCGGTGTCGTTACCGGGGTCCTGGGCTGCCTGCAGGCCTTGGAAGTG
CTGAAAATCGCTGCGGGTCTGGGCCCCTCTTACAGTGGCAGCTTGTTGCTCTTTGATGCC
CTGAGAGGGCATTTCCGCTCTATTCGGCTGCGGAGCCGCAGGCTCGACTGTGCAGCTTGC
GGGGAACGGCCCACTGTGACTGATCTGCTGGACTATGAAGCCTTCTGTGGCTCCTCAGCC
ACTGATAAATGCCGCTCCCTGCAACTACTGAGCCCAGAGGAGCGTGTTTCTGTCACCGAC
TATAAGCGACTGCTGGATTCTGGGGCATTCCACCTGTTGCTGGACGTCAGGCCTCAGGTG
GAGGTGGACATTTGTCGTTTGCCTCATGCCCTACACATCCCTCTGAAACATTTGGAACGC
AGGGATGCGGAGAGCCTGAAACTCTTAAAAGAAGCAATCTGGGAAGAGAAGCAGGGCACA
CAAGAAGGGGCTGCTGTCCCCATTTATGTGATTTGCAAACTGGGAAATGACTCACAGAAA
GCCGTGAAGATCCTCCAGTCCTTATCAGCAGCTCAAGAGTTAGACCCTTTAACAGTTCGG
GATGTTGTGGGGGGCCTCATGGCCTGGGCTGCCAAAATCGATGGAACATTTCCACAGTAC
TGA
Protein Properties
Number of Residues 460
Molecular Weight 49668.685
Theoretical pI 6.209
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>Adenylyltransferase and sulfurtransferase MOCS3
MASREEVLALQAEVAQREEELNSLKQKLASALLAEQEPQPERLVPVSPLPPKAALSRDEI
LRYSRQLVLPELGVHGQLRLGTACVLIVGCGGLGCPLAQYLAAAGVGRLGLVDYDVVEMS
NLARQVLHGEALAGQAKAFSAAASLRRLNSAVECVPYTQALTPATALDLVRRYDVVADCS
DNVPTRYLVNDACVLAGRPLVSASALRFEGQITVYHYDGGPCYRCIFPQPPPAETVTNCA
DGGVLGVVTGVLGCLQALEVLKIAAGLGPSYSGSLLLFDALRGHFRSIRLRSRRLDCAAC
GERPTVTDLLDYEAFCGSSATDKCRSLQLLSPEERVSVTDYKRLLDSGAFHLLLDVRPQV
EVDICRLPHALHIPLKHLERRDAESLKLLKEAIWEEKQGTQEGAAVPIYVICKLGNDSQK
AVKILQSLSAAQELDPLTVRDVVGGLMAWAAKIDGTFPQY
GenBank ID Protein 3851719
UniProtKB/Swiss-Prot ID O95396
UniProtKB/Swiss-Prot Entry Name MOCS3_HUMAN
PDB IDs
GenBank Gene ID AF102544
GeneCard ID MOCS3
GenAtlas ID MOCS3
HGNC ID HGNC:15765
References
General References
  1. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  2. Deloukas P, Matthews LH, Ashurst J, Burton J, Gilbert JG, Jones M, Stavrides G, Almeida JP, Babbage AK, Bagguley CL, Bailey J, Barlow KF, Bates KN, Beard LM, Beare DM, Beasley OP, Bird CP, Blakey SE, Bridgeman AM, Brown AJ, Buck D, Burrill W, Butler AP, Carder C, Carter NP, Chapman JC, Clamp M, Clark G, Clark LN, Clark SY, Clee CM, Clegg S, Cobley VE, Collier RE, Connor R, Corby NR, Coulson A, Coville GJ, Deadman R, Dhami P, Dunn M, Ellington AG, Frankland JA, Fraser A, French L, Garner P, Grafham DV, Griffiths C, Griffiths MN, Gwilliam R, Hall RE, Hammond S, Harley JL, Heath PD, Ho S, Holden JL, Howden PJ, Huckle E, Hunt AR, Hunt SE, Jekosch K, Johnson CM, Johnson D, Kay MP, Kimberley AM, King A, Knights A, Laird GK, Lawlor S, Lehvaslaiho MH, Leversha M, Lloyd C, Lloyd DM, Lovell JD, Marsh VL, Martin SL, McConnachie LJ, McLay K, McMurray AA, Milne S, Mistry D, Moore MJ, Mullikin JC, Nickerson T, Oliver K, Parker A, Patel R, Pearce TA, Peck AI, Phillimore BJ, Prathalingam SR, Plumb RW, Ramsay H, Rice CM, Ross MT, Scott CE, Sehra HK, Shownkeen R, Sims S, Skuce CD, Smith ML, Soderlund C, Steward CA, Sulston JE, Swann M, Sycamore N, Taylor R, Tee L, Thomas DW, Thorpe A, Tracey A, Tromans AC, Vaudin M, Wall M, Wallis JM, Whitehead SL, Whittaker P, Willey DL, Williams L, Williams SA, Wilming L, Wray PW, Hubbard T, Durbin RM, Bentley DR, Beck S, Rogers J: The DNA sequence and comparative analysis of human chromosome 20. Nature. 2001 Dec 20-27;414(6866):865-71. [PubMed:11780052 ]
  3. Matthies A, Rajagopalan KV, Mendel RR, Leimkuhler S: Evidence for the physiological role of a rhodanese-like protein for the biosynthesis of the molybdenum cofactor in humans. Proc Natl Acad Sci U S A. 2004 Apr 20;101(16):5946-51. Epub 2004 Apr 8. [PubMed:15073332 ]
  4. Matthies A, Nimtz M, Leimkuhler S: Molybdenum cofactor biosynthesis in humans: identification of a persulfide group in the rhodanese-like domain of MOCS3 by mass spectrometry. Biochemistry. 2005 May 31;44(21):7912-20. [PubMed:15910006 ]
  5. Krepinsky K, Leimkuhler S: Site-directed mutagenesis of the active site loop of the rhodanese-like domain of the human molybdopterin synthase sulfurase MOCS3. Major differences in substrate specificity between eukaryotic and bacterial homologs. FEBS J. 2007 Jun;274(11):2778-87. Epub 2007 Apr 25. [PubMed:17459099 ]
  6. Marelja Z, Stocklein W, Nimtz M, Leimkuhler S: A novel role for human Nfs1 in the cytoplasm: Nfs1 acts as a sulfur donor for MOCS3, a protein involved in molybdenum cofactor biosynthesis. J Biol Chem. 2008 Sep 12;283(37):25178-85. doi: 10.1074/jbc.M804064200. Epub 2008 Jul 23. [PubMed:18650437 ]
  7. Schlieker CD, Van der Veen AG, Damon JR, Spooner E, Ploegh HL: A functional proteomics approach links the ubiquitin-related modifier Urm1 to a tRNA modification pathway. Proc Natl Acad Sci U S A. 2008 Nov 25;105(47):18255-60. doi: 10.1073/pnas.0808756105. Epub 2008 Nov 18. [PubMed:19017811 ]