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Protein

Molybdopterin synthase sulfur carrier subunit

Gene

MOCS2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Acts as a sulfur carrier required for molybdopterin biosynthesis. Component of the molybdopterin synthase complex that catalyzes the conversion of precursor Z into molybdopterin by mediating the incorporation of 2 sulfur atoms into precursor Z to generate a dithiolene group. In the complex, serves as sulfur donor by being thiocarboxylated (-COSH) at its C-terminus by MOCS3. After interaction with MOCS2B, the sulfur is then transferred to precursor Z to form molybdopterin.UniRule annotation1 Publication

Pathwayi: molybdopterin biosynthesis

This protein is involved in the pathway molybdopterin biosynthesis, which is part of Cofactor biosynthesis.UniRule annotation
View all proteins of this organism that are known to be involved in the pathway molybdopterin biosynthesis and in Cofactor biosynthesis.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Molybdenum cofactor biosynthesis

Keywords - Ligandi

Nucleotide-binding

Enzyme and pathway databases

BioCyciMetaCyc:MONOMER-16667.
ReactomeiR-HSA-947581. Molybdenum cofactor biosynthesis.
UniPathwayiUPA00344.

Names & Taxonomyi

Protein namesi
Recommended name:
Molybdopterin synthase sulfur carrier subunitUniRule annotation
Alternative name(s):
MOCO1-A
Molybdenum cofactor synthesis protein 2 small subunitUniRule annotation
Molybdenum cofactor synthesis protein 2AUniRule annotation
Short name:
MOCS2AUniRule annotation
Molybdopterin-synthase small subunit
Sulfur carrier protein MOCS2AUniRule annotation
Gene namesi
Name:MOCS2UniRule annotation
Synonyms:MOCO1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:7193. MOCS2.

Subcellular locationi

  • Cytoplasmcytosol UniRule annotation1 Publication

GO - Cellular componenti

  • cytosol Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • molybdopterin synthase complex Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Molybdenum cofactor deficiency, complementation group B (MOCODB)4 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive metabolic disorder characterized by neonatal onset of intractable seizures, opisthotonus, and facial dysmorphism associated with hypouricemia and elevated urinary sulfite levels. Affected individuals show severe neurologic damage and often die in early childhood.
See also OMIM:252160
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti7 – 71V → F in MOCODB; in a patient with mild form of the disease; impairs interaction with MOCS2B. 2 Publications
VAR_054854

Keywords - Diseasei

Disease mutation

Organism-specific databases

MalaCardsiMOCS2.
MIMi252160. phenotype.
Orphaneti308393. Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B.
PharmGKBiPA30903.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 8888Molybdopterin synthase sulfur carrier subunitPRO_0000209134Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei88 – 8811-thioglycine; alternateUniRule annotation5 Publications
Modified residuei88 – 881Glycyl adenylate; alternateUniRule annotation1 Publication

Post-translational modificationi

C-terminal thiocarboxylation occurs in 2 steps, it is first acyl-adenylated (-COAMP) via the hesA/moeB/thiF part of MOCS3, then thiocarboxylated (-COSH) via the rhodanese domain of MOCS3.UniRule annotation5 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiO96033.
MaxQBiO96033.
PRIDEiO96033.

PTM databases

iPTMnetiO96033.

Expressioni

Tissue specificityi

Widely expressed. Highest levels are found in heart and skeletal muscle. Lower levels are present in brain, kidney and pancreas. Very low levels are found in lung and peripheral blood leukocytes.2 Publications

Gene expression databases

BgeeiO96033.
CleanExiHS_MOCS2.
ExpressionAtlasiO96033. baseline and differential.
GenevisibleiO96033. HS.

Interactioni

Subunit structurei

Heterotetramer; composed of 2 small (MOCS2A) and 2 large (MOCS2B) subunits.UniRule annotation

Protein-protein interaction databases

BioGridi110481. 5 interactions.
IntActiO96033. 3 interactions.
MINTiMINT-1397621.

Structurei

3D structure databases

ProteinModelPortaliO96033.
SMRiO96033. Positions 7-88.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the MoaD family. MOCS2A subfamily.UniRule annotation

Phylogenomic databases

GeneTreeiENSGT00510000047669.
HOGENOMiHOG000280991.
OrthoDBiEOG786H5S.

Family and domain databases

Gene3Di3.10.20.30. 1 hit.
HAMAPiMF_03051. MOCS2A.
InterProiIPR012675. Beta-grasp_dom.
IPR028887. MOCS2A.
IPR010034. Mopterin_su_1.
IPR016155. Mopterin_synth/thiamin_S_b.
IPR003749. ThiS/MoaD.
[Graphical view]
PfamiPF02597. ThiS. 1 hit.
[Graphical view]
SUPFAMiSSF54285. SSF54285. 1 hit.
TIGRFAMsiTIGR01682. moaD. 1 hit.

Sequencei

Sequence statusi: Complete.

O96033-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVPLCQVEVL YFAKSAEITG VRSETISVPQ EIKALQLWKE IETRHPGLAD
60 70 80
VRNQIIFAVR QEYVELGDQL LVLQPGDEIA VIPPISGG
Length:88
Mass (Da):9,755
Last modified:May 1, 1999 - v1
Checksum:iBD08B374B615E7BE
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti7 – 71V → F in MOCODB; in a patient with mild form of the disease; impairs interaction with MOCS2B. 2 Publications
VAR_054854
Natural varianti51 – 511V → A.
Corresponds to variant rs2233210 [ dbSNP | Ensembl ].
VAR_050090

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF091871 mRNA. Translation: AAD14598.1.
AF117815 mRNA. Translation: AAD13296.1.
CCDSiCCDS47205.1.
PIRiA59370.
RefSeqiNP_789776.1. NM_176806.3.
UniGeneiHs.163645.
Hs.594335.

Genome annotation databases

EnsembliENST00000361377; ENSP00000355160; ENSG00000164172.
ENST00000450852; ENSP00000411022; ENSG00000164172.
ENST00000508922; ENSP00000426274; ENSG00000164172.
ENST00000510818; ENSP00000424267; ENSG00000164172.
ENST00000582677; ENSP00000462870; ENSG00000164172.
ENST00000584946; ENSP00000464663; ENSG00000164172.
GeneIDi4338.
UCSCiuc011cqf.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF091871 mRNA. Translation: AAD14598.1.
AF117815 mRNA. Translation: AAD13296.1.
CCDSiCCDS47205.1.
PIRiA59370.
RefSeqiNP_789776.1. NM_176806.3.
UniGeneiHs.163645.
Hs.594335.

3D structure databases

ProteinModelPortaliO96033.
SMRiO96033. Positions 7-88.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi110481. 5 interactions.
IntActiO96033. 3 interactions.
MINTiMINT-1397621.

PTM databases

iPTMnetiO96033.

Proteomic databases

EPDiO96033.
MaxQBiO96033.
PRIDEiO96033.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000361377; ENSP00000355160; ENSG00000164172.
ENST00000450852; ENSP00000411022; ENSG00000164172.
ENST00000508922; ENSP00000426274; ENSG00000164172.
ENST00000510818; ENSP00000424267; ENSG00000164172.
ENST00000582677; ENSP00000462870; ENSG00000164172.
ENST00000584946; ENSP00000464663; ENSG00000164172.
GeneIDi4338.
UCSCiuc011cqf.4. human.

Organism-specific databases

CTDi4338.
GeneCardsiMOCS2.
HGNCiHGNC:7193. MOCS2.
MalaCardsiMOCS2.
MIMi252160. phenotype.
603708. gene.
neXtProtiNX_O96033.
Orphaneti308393. Sulfite oxidase deficiency due to molybdenum cofactor deficiency type B.
PharmGKBiPA30903.
GenAtlasiSearch...

Phylogenomic databases

GeneTreeiENSGT00510000047669.
HOGENOMiHOG000280991.
OrthoDBiEOG786H5S.

Enzyme and pathway databases

UniPathwayiUPA00344.
BioCyciMetaCyc:MONOMER-16667.
ReactomeiR-HSA-947581. Molybdenum cofactor biosynthesis.

Miscellaneous databases

ChiTaRSiMOCS2. human.
GenomeRNAii4338.
SOURCEiSearch...

Gene expression databases

BgeeiO96033.
CleanExiHS_MOCS2.
ExpressionAtlasiO96033. baseline and differential.
GenevisibleiO96033. HS.

Family and domain databases

Gene3Di3.10.20.30. 1 hit.
HAMAPiMF_03051. MOCS2A.
InterProiIPR012675. Beta-grasp_dom.
IPR028887. MOCS2A.
IPR010034. Mopterin_su_1.
IPR016155. Mopterin_synth/thiamin_S_b.
IPR003749. ThiS/MoaD.
[Graphical view]
PfamiPF02597. ThiS. 1 hit.
[Graphical view]
SUPFAMiSSF54285. SSF54285. 1 hit.
TIGRFAMsiTIGR01682. moaD. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Human molybdopterin synthase gene: identification of a bicistronic transcript with overlapping reading frames."
    Stallmeyer B., Drugeon G., Reiss J., Haenni A.L., Mendel R.R.
    Am. J. Hum. Genet. 64:698-705(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], IDENTIFICATION OF BICISTRONIC GENE, TISSUE SPECIFICITY.
    Tissue: Liver.
  2. "The two subunits of human molybdopterin synthase: evidence for a bicistronic messenger RNA with overlapping reading frames."
    Sloan J., Kinghorn J.R., Unkles S.E.
    Nucleic Acids Res. 27:854-858(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
  3. "Mechanistic studies of human molybdopterin synthase reaction and characterization of mutants identified in group B patients of molybdenum cofactor deficiency."
    Leimkuehler S., Freuer A., Araujo J.A., Rajagopalan K.V., Mendel R.R.
    J. Biol. Chem. 278:26127-26134(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBUNIT, THIOCARBOXYLATION AT GLY-88, CHARACTERIZATION OF VARIANT MOCODB PHE-7.
  4. "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: SUBCELLULAR LOCATION, AMPYLATION AT GLY-88, THIOCARBOXYLATION AT GLY-88.
  5. "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: THIOCARBOXYLATION AT GLY-88.
  6. "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: THIOCARBOXYLATION AT GLY-88.
  7. "The sulfurtransferase activity of Uba4 presents a link between ubiquitin-like protein conjugation and activation of sulfur carrier proteins."
    Schmitz J., Chowdhury M.M., Haenzelmann P., Nimtz M., Lee E.Y., Schindelin H., Leimkuehler S.
    Biochemistry 47:6479-6489(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: THIOCARBOXYLATION AT GLY-88.
  8. "Human molybdopterin synthase gene: genomic structure and mutations in molybdenum cofactor deficiency type B."
    Reiss J., Dorche C., Stallmeyer B., Mendel R.R., Cohen N., Zabot M.-T.
    Am. J. Hum. Genet. 64:706-711(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN MOCODB.
  9. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  10. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.
  11. "Molybdopterin synthase mutations in a mild case of molybdenum cofactor deficiency."
    Johnson J.L., Coyne K.E., Rajagopalan K.V., Van Hove J.L.K., Mackay M., Pitt J., Boneh A.
    Am. J. Med. Genet. 104:169-173(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT MOCODB PHE-7.
  12. "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."
    Leimkuehler S., Charcosset M., Latour P., Dorche C., Kleppe S., Scaglia F., Szymczak I., Schupp P., Hahnewald R., Reiss J.
    Hum. Genet. 117:565-570(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN MOCODB.
  13. "A novel MOCS2 mutation reveals coordinated expression of the small and large subunit of molybdopterin synthase."
    Hahnewald R., Leimkuehler S., Vilaseca A., Acquaviva-Bourdain C., Lenz U., Reiss J.
    Mol. Genet. Metab. 89:210-213(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN MOCODB.

Entry informationi

Entry nameiMOC2A_HUMAN
AccessioniPrimary (citable) accession number: O96033
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 11, 2002
Last sequence update: May 1, 1999
Last modified: June 8, 2016
This is version 128 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Miscellaneous

This protein is produced by a bicistronic gene which also produces the large subunit (MOCS2B) from an overlapping reading frame. Expression of these 2 proteins are related since a mutation that removes the start codon of the small subunit (MOCS2A) also impairs expression of the large subunit (MOCS2B).

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.