Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

O95396 (MOCS3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Adenylyltransferase and sulfurtransferase MOCS3
Alternative name(s):
Molybdenum cofactor synthesis protein 3
Molybdopterin synthase sulfurylase
Short name=MPT synthase sulfurylase

Including the following 2 domains:

  1. Molybdopterin-synthase adenylyltransferase
    EC=2.7.7.80
    Alternative name(s):
    Adenylyltransferase MOCS3
    Sulfur carrier protein MOCS2A adenylyltransferase
  2. Molybdopterin-synthase sulfurtransferase
    EC=2.8.1.11
    Alternative name(s):
    Sulfur carrier protein MOCS2A sulfurtransferase
    Sulfurtransferase MOCS3
Gene names
Name:MOCS3
Synonyms:UBA4
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length460 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Plays a central role in 2-thiolation of mcm5S2U at tRNA wobble positions of cytosolic 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. Ref.1 Ref.7

Catalytic activity

ATP + [molybdopterin-synthase sulfur-carrier protein]-Gly-Gly = diphosphate + [molybdopterin-synthase sulfur-carrier protein]-Gly-Gly-AMP. Ref.5 Ref.6

[Molybdopterin-synthase sulfur-carrier protein]-Gly-Gly-AMP + [cysteine desulfurase]-S-sulfanyl-L-cysteine = AMP + [molybdopterin-synthase sulfur-carrier protein]-Gly-NH-CH(2)-C(O)SH + cysteine desulfurase. Ref.5 Ref.6

Cofactor

Binds 1 zinc ion per subunit By similarity. HAMAP-Rule MF_03049

Pathway

tRNA modification; 5-methoxycarbonylmethyl-2-thiouridine-tRNA biosynthesis. HAMAP-Rule MF_03049

Cofactor biosynthesis; molybdopterin biosynthesis. HAMAP-Rule MF_03049

Subunit structure

Interacts with NFS1. Ref.6

Subcellular location

Cytoplasm Ref.1.

Sequence similarities

In the N-terminal section; belongs to the HesA/MoeB/ThiF family. UBA4 subfamily.

Contains 1 rhodanese domain.

Biophysicochemical properties

Kinetic parameters:

KM=0.25 mM for thiosulfate Ref.1

KM=0.28 mM for cyanide

Ontologies

Keywords
   Biological processMolybdenum cofactor biosynthesis
tRNA processing
   Cellular componentCytoplasm
   Coding sequence diversityPolymorphism
   LigandATP-binding
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionTransferase
   PTMDisulfide bond
   Technical term3D-structure
Complete proteome
Multifunctional enzyme
Reference proteome
Gene Ontology (GO)
   Biological_processMo-molybdopterin cofactor biosynthetic process

Inferred from direct assay Ref.1. Source: UniProtKB

enzyme active site formation via L-cysteine persulfide

Inferred from direct assay Ref.4. Source: UniProtKB

molybdopterin cofactor biosynthetic process

Traceable author statement. Source: Reactome

small molecule metabolic process

Traceable author statement. Source: Reactome

tRNA thio-modification

Inferred from direct assay Ref.7. Source: UniProtKB

tRNA wobble position uridine thiolation

Inferred from electronic annotation. Source: InterPro

tRNA wobble uridine modification

Inferred from direct assay Ref.7. Source: UniProtKB

vitamin metabolic process

Traceable author statement. Source: Reactome

water-soluble vitamin metabolic process

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Inferred from direct assay Ref.1. Source: UniProtKB

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

URM1 activating enzyme activity

Inferred from direct assay Ref.7. Source: UniProtKB

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

molybdopterin-synthase adenylyltransferase activity

Inferred from electronic annotation. Source: UniProtKB-EC

molybdopterin-synthase sulfurtransferase activity

Inferred from electronic annotation. Source: UniProtKB-EC

nucleotidyltransferase activity

Inferred from direct assay Ref.7. Source: UniProtKB

sulfurtransferase activity

Inferred from direct assay Ref.4Ref.6Ref.7. Source: UniProtKB

thiosulfate sulfurtransferase activity

Inferred from mutant phenotype Ref.1Ref.5. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 460460Adenylyltransferase and sulfurtransferase MOCS3 HAMAP-Rule MF_03049
PRO_0000120583

Regions

Domain347 – 458112Rhodanese
Nucleotide binding120 – 1245ATP By similarity
Nucleotide binding181 – 1822ATP By similarity

Sites

Active site2391Glycyl thioester intermediate; for adenylyltransferase activity By similarity
Active site4121Cysteine persulfide intermediate; for sulfurtransferase activity Ref.4
Metal binding2221Zinc By similarity
Metal binding2251Zinc By similarity
Metal binding2971Zinc By similarity
Metal binding3001Zinc By similarity
Binding site921ATP; via amide nitrogen By similarity
Binding site1131ATP By similarity
Binding site1371ATP By similarity

Amino acid modifications

Disulfide bond316 ↔ 324 Ref.4

Natural variations

Natural variant4291S → A.
Corresponds to variant rs7269297 [ dbSNP | Ensembl ].
VAR_049349

Experimental info

Mutagenesis2391C → A: Impairs sulfurtransferase activity. Ref.1
Mutagenesis3161C → A: Does not affect sulfurtransferase activity. Ref.1
Mutagenesis3241C → A: Does not affect sulfurtransferase activity. Ref.1
Mutagenesis3651C → A: Does not affect sulfurtransferase activity. Ref.1
Mutagenesis4121C → A: Abolishes sulfurtransferase activity. Ref.1
Mutagenesis4131K → R: Does not affect sulfurtransferase specificity and activity. Ref.5
Mutagenesis4141L → K: Does not affect sulfurtransferase specificity and activity. Ref.5
Mutagenesis4151G → A: Does not affect sulfurtransferase specificity and activity. Ref.5
Mutagenesis4161N → V: Does not affect sulfurtransferase specificity and activity. Ref.5
Mutagenesis4171D → R: Results in 470-fold increased activity. Ref.5
Mutagenesis4171D → T: Results in 90-fold increased activity. Ref.5
Mutagenesis4581P → G: Does not affect sulfurtransferase specificity and activity. Ref.5
Mutagenesis4601Y → A: Does not affect sulfurtransferase specificity and activity. Ref.5

Secondary structure

........................ 460
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O95396 [UniParc].

Last modified May 1, 1999. Version 1.
Checksum: 299A4E755173E324

FASTA46049,669
        10         20         30         40         50         60 
MASREEVLAL QAEVAQREEE LNSLKQKLAS ALLAEQEPQP ERLVPVSPLP PKAALSRDEI 

        70         80         90        100        110        120 
LRYSRQLVLP ELGVHGQLRL GTACVLIVGC GGLGCPLAQY LAAAGVGRLG LVDYDVVEMS 

       130        140        150        160        170        180 
NLARQVLHGE ALAGQAKAFS AAASLRRLNS AVECVPYTQA LTPATALDLV RRYDVVADCS 

       190        200        210        220        230        240 
DNVPTRYLVN DACVLAGRPL VSASALRFEG QITVYHYDGG PCYRCIFPQP PPAETVTNCA 

       250        260        270        280        290        300 
DGGVLGVVTG VLGCLQALEV LKIAAGLGPS YSGSLLLFDA LRGHFRSIRL RSRRLDCAAC 

       310        320        330        340        350        360 
GERPTVTDLL DYEAFCGSSA TDKCRSLQLL SPEERVSVTD YKRLLDSGAF HLLLDVRPQV 

       370        380        390        400        410        420 
EVDICRLPHA LHIPLKHLER RDAESLKLLK EAIWEEKQGT QEGAAVPIYV ICKLGNDSQK 

       430        440        450        460 
AVKILQSLSA AQELDPLTVR DVVGGLMAWA AKIDGTFPQY 

« Hide

References

« Hide 'large scale' references
[1]"Evidence for the physiological role of a rhodanese-like protein for the biosynthesis of the molybdenum cofactor in humans."
Matthies A., Rajagopalan K.V., Mendel R.R., Leimkuehler S.
Proc. Natl. Acad. Sci. U.S.A. 101:5946-5951(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN BIOSYNTHESIS OF THE MOLYBDENUM COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, MUTAGENESIS OF CYS-239; CYS-316; CYS-324; CYS-365 AND CYS-412.
[2]"The DNA sequence and comparative analysis of human chromosome 20."
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. expand/collapse author list , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[3]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Uterus.
[4]"Molybdenum cofactor biosynthesis in humans: identification of a persulfide group in the rhodanese-like domain of MOCS3 by mass spectrometry."
Matthies A., Nimtz M., Leimkuehler S.
Biochemistry 44:7912-7920(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: ACTIVE SITE, DISULFIDE BOND.
[5]"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."
Krepinsky K., Leimkuehler S.
FEBS J. 274:2778-2787(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME ACTIVITY, MUTAGENESIS OF LYS-413; LEU-414; GLY-415; ASN-416; ASP-417; PRO-458 AND TYR-460.
[6]"A novel role for human Nfs1 in the cytoplasm: Nfs1 acts as a sulfur donor for MOCS3, a protein involved in molybdenum cofactor biosynthesis."
Marelja Z., Stoecklein W., Nimtz M., Leimkuehler S.
J. Biol. Chem. 283:25178-25185(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME ACTIVITY, INTERACTION WITH NFS1.
[7]"A functional proteomics approach links the ubiquitin-related modifier Urm1 to a tRNA modification pathway."
Schlieker C.D., Van der Veen A.G., Damon J.R., Spooner E., Ploegh H.L.
Proc. Natl. Acad. Sci. U.S.A. 105:18255-18260(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN 2-THIOLATION OF TRNA.
[8]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[9]"Crystal structure of the human MOCS3 rhodanese-like domain."
Structural genomics consortium (SGC)
Submitted (JUL-2009) to the PDB data bank
Cited for: X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) OF 335-460.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF102544 mRNA. Translation: AAC72412.1.
AL034553 Genomic DNA. Translation: CAB53750.1.
BC015939 mRNA. Translation: AAH15939.1.
RefSeqNP_055299.1. NM_014484.4.
UniGeneHs.159410.
Hs.736268.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3I2VX-ray1.25A335-460[»]
ProteinModelPortalO95396.
SMRO95396. Positions 5-301, 335-460.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid118127. 4 interactions.
DIPDIP-31168N.
IntActO95396. 1 interaction.
MINTMINT-5003967.
STRING9606.ENSP00000244051.

PTM databases

PhosphoSiteO95396.

Proteomic databases

PaxDbO95396.
PeptideAtlasO95396.
PRIDEO95396.

Protocols and materials databases

DNASU27304.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000244051; ENSP00000244051; ENSG00000124217.
GeneID27304.
KEGGhsa:27304.
UCSCuc002xvy.2. human.

Organism-specific databases

CTD27304.
GeneCardsGC20P049575.
HGNCHGNC:15765. MOCS3.
HPAHPA027556.
MIM609277. gene.
neXtProtNX_O95396.
Orphanet99732. Sulfite oxidase deficiency due to molybdenum cofactor deficiency.
PharmGKBPA30904.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0476.
HOGENOMHOG000281219.
HOVERGENHBG052491.
InParanoidO95396.
KOK11996.
OMAEAFCGSS.
OrthoDBEOG776SQ3.
PhylomeDBO95396.
TreeFamTF106103.

Enzyme and pathway databases

BioCycMetaCyc:HS04742-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
UniPathwayUPA00344.
UPA00988.

Gene expression databases

BgeeO95396.
CleanExHS_MOCS3.
GenevestigatorO95396.

Family and domain databases

Gene3D3.40.250.10. 1 hit.
3.40.50.720. 1 hit.
HAMAPMF_03049. MOCS3_Uba4.
InterProIPR028885. MOCS3/Uba4.
IPR007901. MoeZ_MoeB.
IPR009036. Molybdenum_cofac_synth_MoeB.
IPR016040. NAD(P)-bd_dom.
IPR001763. Rhodanese-like_dom.
IPR000594. ThiF_NAD_FAD-bd.
[Graphical view]
PfamPF05237. MoeZ_MoeB. 1 hit.
PF00581. Rhodanese. 1 hit.
PF00899. ThiF. 1 hit.
[Graphical view]
SMARTSM00450. RHOD. 1 hit.
[Graphical view]
SUPFAMSSF69572. SSF69572. 1 hit.
PROSITEPS50206. RHODANESE_3. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO95396.
GeneWikiMOCS3.
GenomeRNAi27304.
NextBio50301.
PROO95396.
SOURCESearch...

Entry information

Entry nameMOCS3_HUMAN
AccessionPrimary (citable) accession number: O95396
Entry history
Integrated into UniProtKB/Swiss-Prot: July 26, 2002
Last sequence update: May 1, 1999
Last modified: April 16, 2014
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM