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Protein

Adenylyltransferase and sulfurtransferase MOCS3

Gene

MOCS3

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

Functioni

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.UniRule annotation2 Publications

Catalytic activityi

ATP + [molybdopterin-synthase sulfur-carrier protein]-Gly-Gly = diphosphate + [molybdopterin-synthase sulfur-carrier protein]-Gly-Gly-AMP.UniRule annotation3 Publications
[Molybdopterin-synthase sulfur-carrier protein]-Gly-Gly-AMP + [cysteine desulfurase]-S-sulfanyl-L-cysteine + reduced acceptor = AMP + [molybdopterin-synthase sulfur-carrier protein]-Gly-NH-CH(2)-C(O)SH + [cysteine desulfurase] + oxidized acceptor.UniRule annotation3 Publications

Cofactori

Zn2+UniRule annotationNote: Binds 1 zinc ion per subunit.UniRule annotation

Kineticsi

  1. KM=0.25 mM for thiosulfate1 Publication
  2. KM=0.28 mM for cyanide1 Publication

    Pathwayi: 5-methoxycarbonylmethyl-2-thiouridine-tRNA biosynthesis

    This protein is involved in the pathway 5-methoxycarbonylmethyl-2-thiouridine-tRNA biosynthesis, which is part of tRNA modification.UniRule annotation
    View all proteins of this organism that are known to be involved in the pathway 5-methoxycarbonylmethyl-2-thiouridine-tRNA biosynthesis and in tRNA modification.

    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.

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei92ATP; via amide nitrogenUniRule annotation1
    Binding sitei113ATPUniRule annotation1
    Binding sitei137ATPUniRule annotation1
    Metal bindingi222ZincUniRule annotation1
    Metal bindingi225ZincUniRule annotation1
    Active sitei239Glycyl thioester intermediate; for adenylyltransferase activityUniRule annotation1
    Metal bindingi297ZincUniRule annotation1
    Metal bindingi300ZincUniRule annotation1
    Active sitei412Cysteine persulfide intermediate; for sulfurtransferase activityUniRule annotation1 Publication1

    Regions

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Nucleotide bindingi120 – 124ATPUniRule annotation5
    Nucleotide bindingi181 – 182ATPUniRule annotation2

    GO - Molecular functioni

    • ATP binding Source: UniProtKB-KW
    • metal ion binding Source: UniProtKB-KW
    • molybdopterin-synthase adenylyltransferase activity Source: UniProtKB-EC
    • molybdopterin-synthase sulfurtransferase activity Source: UniProtKB-EC
    • nucleotidyltransferase activity Source: UniProtKB
    • protein adenylyltransferase activity Source: GO_Central
    • sulfurtransferase activity Source: UniProtKB
    • thiosulfate sulfurtransferase activity Source: UniProtKB
    • URM1 activating enzyme activity Source: UniProtKB

    GO - Biological processi

    • enzyme active site formation via cysteine modification to L-cysteine persulfide Source: UniProtKB
    • molybdopterin cofactor biosynthetic process Source: Reactome
    • Mo-molybdopterin cofactor biosynthetic process Source: UniProtKB
    • protein urmylation Source: GO_Central
    • tRNA thio-modification Source: UniProtKB
    • tRNA wobble position uridine thiolation Source: GO_Central
    • tRNA wobble uridine modification Source: UniProtKB
    Complete GO annotation...

    Keywords - Molecular functioni

    Transferase

    Keywords - Biological processi

    Molybdenum cofactor biosynthesis, tRNA processing

    Keywords - Ligandi

    ATP-binding, Metal-binding, Nucleotide-binding, Zinc

    Enzyme and pathway databases

    BioCyciMetaCyc:HS04742-MONOMER.
    ZFISH:HS04742-MONOMER.
    BRENDAi2.7.7.80. 2681.
    2.8.1.11. 2681.
    ReactomeiR-HSA-947581. Molybdenum cofactor biosynthesis.
    UniPathwayiUPA00344.
    UPA00988.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Adenylyltransferase and sulfurtransferase MOCS3UniRule annotation
    Alternative name(s):
    Molybdenum cofactor synthesis protein 3UniRule annotation
    Molybdopterin synthase sulfurylase
    Short name:
    MPT synthase sulfurylase
    Including the following 2 domains:
    Molybdopterin-synthase adenylyltransferaseUniRule annotation (EC:2.7.7.80UniRule annotation3 Publications)
    Alternative name(s):
    Adenylyltransferase MOCS3UniRule annotation
    Sulfur carrier protein MOCS2A adenylyltransferaseUniRule annotation
    Molybdopterin-synthase sulfurtransferaseUniRule annotation (EC:2.8.1.11UniRule annotation3 Publications)
    Alternative name(s):
    Sulfur carrier protein MOCS2A sulfurtransferaseUniRule annotation
    Sulfurtransferase MOCS3UniRule annotation
    Gene namesi
    Name:MOCS3UniRule annotation
    Synonyms:UBA4UniRule annotation
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 20

    Organism-specific databases

    HGNCiHGNC:15765. MOCS3.

    Subcellular locationi

    • Cytoplasm UniRule annotation1 Publication

    GO - Cellular componenti

    • cytosol Source: UniProtKB
    Complete GO annotation...

    Keywords - Cellular componenti

    Cytoplasm

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi239C → A: Impairs sulfurtransferase activity. 1 Publication1
    Mutagenesisi316C → A: Does not affect sulfurtransferase activity. 1 Publication1
    Mutagenesisi324C → A: Does not affect sulfurtransferase activity. 1 Publication1
    Mutagenesisi365C → A: Does not affect sulfurtransferase activity. 1 Publication1
    Mutagenesisi412C → A: Abolishes sulfurtransferase activity. 1 Publication1
    Mutagenesisi413K → R: Does not affect sulfurtransferase specificity and activity. 1 Publication1
    Mutagenesisi414L → K: Does not affect sulfurtransferase specificity and activity. 1 Publication1
    Mutagenesisi415G → A: Does not affect sulfurtransferase specificity and activity. 1 Publication1
    Mutagenesisi416N → V: Does not affect sulfurtransferase specificity and activity. 1 Publication1
    Mutagenesisi417D → R: Results in 470-fold increased activity. 1 Publication1
    Mutagenesisi417D → T: Results in 90-fold increased activity. 1 Publication1
    Mutagenesisi458P → G: Does not affect sulfurtransferase specificity and activity. 1 Publication1
    Mutagenesisi460Y → A: Does not affect sulfurtransferase specificity and activity. 1 Publication1

    Organism-specific databases

    OpenTargetsiENSG00000124217.
    PharmGKBiPA30904.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001205831 – 460Adenylyltransferase and sulfurtransferase MOCS3Add BLAST460

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Disulfide bondi316 ↔ 3241 Publication

    Keywords - PTMi

    Disulfide bond

    Proteomic databases

    EPDiO95396.
    MaxQBiO95396.
    PaxDbiO95396.
    PeptideAtlasiO95396.
    PRIDEiO95396.

    PTM databases

    iPTMnetiO95396.
    PhosphoSitePlusiO95396.

    Expressioni

    Gene expression databases

    BgeeiENSG00000124217.
    CleanExiHS_MOCS3.
    GenevisibleiO95396. HS.

    Interactioni

    Subunit structurei

    Interacts with NFS1.UniRule annotation1 Publication

    Protein-protein interaction databases

    BioGridi118127. 17 interactors.
    DIPiDIP-31168N.
    IntActiO95396. 1 interactor.
    MINTiMINT-5003967.
    STRINGi9606.ENSP00000244051.

    Structurei

    Secondary structure

    1460
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi338 – 347Combined sources10
    Beta strandi352 – 355Combined sources4
    Helixi359 – 364Combined sources6
    Beta strandi370 – 372Combined sources3
    Helixi375 – 379Combined sources5
    Helixi383 – 397Combined sources15
    Beta strandi406 – 411Combined sources6
    Beta strandi413 – 416Combined sources4
    Helixi417 – 430Combined sources14
    Beta strandi433 – 435Combined sources3
    Beta strandi437 – 442Combined sources6
    Helixi445 – 452Combined sources8

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3I2VX-ray1.25A335-460[»]
    ProteinModelPortaliO95396.
    SMRiO95396.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiO95396.

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Domaini347 – 458RhodaneseUniRule annotationAdd BLAST112

    Sequence similaritiesi

    In the N-terminal section; belongs to the HesA/MoeB/ThiF family. UBA4 subfamily.UniRule annotation
    Contains 1 rhodanese domain.UniRule annotation

    Phylogenomic databases

    eggNOGiKOG2017. Eukaryota.
    COG0476. LUCA.
    COG0607. LUCA.
    GeneTreeiENSGT00810000125467.
    HOGENOMiHOG000281219.
    HOVERGENiHBG052491.
    InParanoidiO95396.
    KOiK11996.
    OMAiVRNPNEY.
    OrthoDBiEOG091G0EQP.
    PhylomeDBiO95396.
    TreeFamiTF106103.

    Family and domain databases

    Gene3Di3.40.250.10. 1 hit.
    3.40.50.720. 1 hit.
    HAMAPiMF_03049. MOCS3_Uba4. 1 hit.
    InterProiIPR028885. MOCS3/Uba4.
    IPR016040. NAD(P)-bd_dom.
    IPR001763. Rhodanese-like_dom.
    IPR000594. ThiF_NAD_FAD-bd.
    [Graphical view]
    PfamiPF00581. Rhodanese. 1 hit.
    PF00899. ThiF. 1 hit.
    [Graphical view]
    SMARTiSM00450. RHOD. 1 hit.
    [Graphical view]
    SUPFAMiSSF69572. SSF69572. 1 hit.
    PROSITEiPS50206. RHODANESE_3. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    O95396-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MASREEVLAL QAEVAQREEE LNSLKQKLAS ALLAEQEPQP ERLVPVSPLP
    60 70 80 90 100
    PKAALSRDEI LRYSRQLVLP ELGVHGQLRL GTACVLIVGC GGLGCPLAQY
    110 120 130 140 150
    LAAAGVGRLG LVDYDVVEMS NLARQVLHGE ALAGQAKAFS AAASLRRLNS
    160 170 180 190 200
    AVECVPYTQA LTPATALDLV RRYDVVADCS DNVPTRYLVN DACVLAGRPL
    210 220 230 240 250
    VSASALRFEG QITVYHYDGG PCYRCIFPQP PPAETVTNCA DGGVLGVVTG
    260 270 280 290 300
    VLGCLQALEV LKIAAGLGPS YSGSLLLFDA LRGHFRSIRL RSRRLDCAAC
    310 320 330 340 350
    GERPTVTDLL DYEAFCGSSA TDKCRSLQLL SPEERVSVTD YKRLLDSGAF
    360 370 380 390 400
    HLLLDVRPQV EVDICRLPHA LHIPLKHLER RDAESLKLLK EAIWEEKQGT
    410 420 430 440 450
    QEGAAVPIYV ICKLGNDSQK AVKILQSLSA AQELDPLTVR DVVGGLMAWA
    460
    AKIDGTFPQY
    Length:460
    Mass (Da):49,669
    Last modified:May 1, 1999 - v1
    Checksum:i299A4E755173E324
    GO

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_049349429S → A.Corresponds to variant rs7269297dbSNPEnsembl.1

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF102544 mRNA. Translation: AAC72412.1.
    AL034553 Genomic DNA. Translation: CAB53750.1.
    BC015939 mRNA. Translation: AAH15939.1.
    CCDSiCCDS13435.1.
    RefSeqiNP_055299.1. NM_014484.4.
    UniGeneiHs.159410.
    Hs.736268.

    Genome annotation databases

    EnsembliENST00000244051; ENSP00000244051; ENSG00000124217.
    GeneIDi27304.
    KEGGihsa:27304.
    UCSCiuc002xvy.3. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF102544 mRNA. Translation: AAC72412.1.
    AL034553 Genomic DNA. Translation: CAB53750.1.
    BC015939 mRNA. Translation: AAH15939.1.
    CCDSiCCDS13435.1.
    RefSeqiNP_055299.1. NM_014484.4.
    UniGeneiHs.159410.
    Hs.736268.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    3I2VX-ray1.25A335-460[»]
    ProteinModelPortaliO95396.
    SMRiO95396.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi118127. 17 interactors.
    DIPiDIP-31168N.
    IntActiO95396. 1 interactor.
    MINTiMINT-5003967.
    STRINGi9606.ENSP00000244051.

    PTM databases

    iPTMnetiO95396.
    PhosphoSitePlusiO95396.

    Proteomic databases

    EPDiO95396.
    MaxQBiO95396.
    PaxDbiO95396.
    PeptideAtlasiO95396.
    PRIDEiO95396.

    Protocols and materials databases

    DNASUi27304.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000244051; ENSP00000244051; ENSG00000124217.
    GeneIDi27304.
    KEGGihsa:27304.
    UCSCiuc002xvy.3. human.

    Organism-specific databases

    CTDi27304.
    GeneCardsiMOCS3.
    HGNCiHGNC:15765. MOCS3.
    MIMi609277. gene.
    neXtProtiNX_O95396.
    OpenTargetsiENSG00000124217.
    PharmGKBiPA30904.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG2017. Eukaryota.
    COG0476. LUCA.
    COG0607. LUCA.
    GeneTreeiENSGT00810000125467.
    HOGENOMiHOG000281219.
    HOVERGENiHBG052491.
    InParanoidiO95396.
    KOiK11996.
    OMAiVRNPNEY.
    OrthoDBiEOG091G0EQP.
    PhylomeDBiO95396.
    TreeFamiTF106103.

    Enzyme and pathway databases

    UniPathwayiUPA00344.
    UPA00988.
    BioCyciMetaCyc:HS04742-MONOMER.
    ZFISH:HS04742-MONOMER.
    BRENDAi2.7.7.80. 2681.
    2.8.1.11. 2681.
    ReactomeiR-HSA-947581. Molybdenum cofactor biosynthesis.

    Miscellaneous databases

    EvolutionaryTraceiO95396.
    GeneWikiiMOCS3.
    GenomeRNAii27304.
    PROiO95396.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000124217.
    CleanExiHS_MOCS3.
    GenevisibleiO95396. HS.

    Family and domain databases

    Gene3Di3.40.250.10. 1 hit.
    3.40.50.720. 1 hit.
    HAMAPiMF_03049. MOCS3_Uba4. 1 hit.
    InterProiIPR028885. MOCS3/Uba4.
    IPR016040. NAD(P)-bd_dom.
    IPR001763. Rhodanese-like_dom.
    IPR000594. ThiF_NAD_FAD-bd.
    [Graphical view]
    PfamiPF00581. Rhodanese. 1 hit.
    PF00899. ThiF. 1 hit.
    [Graphical view]
    SMARTiSM00450. RHOD. 1 hit.
    [Graphical view]
    SUPFAMiSSF69572. SSF69572. 1 hit.
    PROSITEiPS50206. RHODANESE_3. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiMOCS3_HUMAN
    AccessioniPrimary (citable) accession number: O95396
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: July 26, 2002
    Last sequence update: May 1, 1999
    Last modified: November 2, 2016
    This is version 150 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

    Keywords - Technical termi

    3D-structure, Complete proteome, Multifunctional enzyme, Reference proteome

    Documents

    1. Human chromosome 20
      Human chromosome 20: 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. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    7. 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.