UniProtKB - O95396 (MOCS3_HUMAN)
Protein
Adenylyltransferase and sulfurtransferase MOCS3
Gene
MOCS3
Organism
Homo sapiens (Human)
Status
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
- [molybdopterin-synthase sulfur-carrier protein]-C-terminal Gly-Gly + ATP + H+ = [molybdopterin-synthase sulfur-carrier protein]-C-terminal Gly-Gly-AMP + diphosphateUniRule annotation3 PublicationsEC:2.7.7.80UniRule annotation3 Publications
- [molybdopterin-synthase sulfur-carrier protein]-C-terminal Gly-Gly-AMP + AH2 + S-sulfanyl-L-cysteinyl-[cysteine desulfurase] = [molybdopterin-synthase sulfur-carrier protein]-C-terminal Gly-NH-CH2-C(O)SH + A + AMP + H+ + L-cysteinyl-[cysteine desulfurase]UniRule annotation3 PublicationsEC:2.8.1.11UniRule annotation3 Publications
Cofactori
Zn2+UniRule annotationNote: Binds 1 zinc ion per subunit.UniRule annotation
Kineticsi
- KM=0.25 mM for thiosulfate1 Publication
- KM=0.28 mM for cyanide1 Publication
: 5-methoxycarbonylmethyl-2-thiouridine-tRNA biosynthesis Pathwayi
This protein is involved in the pathway 5-methoxycarbonylmethyl-2-thiouridine-tRNA biosynthesis, which is part of tRNA modification.UniRule annotationView 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 annotationView all proteins of this organism that are known to be involved in the pathway molybdopterin biosynthesis and in Cofactor biosynthesis.
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 92 | ATP; via amide nitrogenUniRule annotation | 1 | |
Binding sitei | 113 | ATPUniRule annotation | 1 | |
Binding sitei | 137 | ATPUniRule annotation | 1 | |
Metal bindingi | 222 | ZincUniRule annotation | 1 | |
Metal bindingi | 225 | ZincUniRule annotation | 1 | |
Active sitei | 239 | Glycyl thioester intermediate; for adenylyltransferase activityUniRule annotation | 1 | |
Metal bindingi | 297 | ZincUniRule annotation | 1 | |
Metal bindingi | 300 | ZincUniRule annotation | 1 | |
Active sitei | 412 | Cysteine persulfide intermediate; for sulfurtransferase activityUniRule annotation1 Publication | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 120 – 124 | ATPUniRule annotation | 5 | |
Nucleotide bindingi | 181 – 182 | ATPUniRule annotation | 2 |
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
- 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
Keywordsi
Molecular function | Multifunctional enzyme, Transferase |
Biological process | Molybdenum cofactor biosynthesis, tRNA processing |
Ligand | ATP-binding, Metal-binding, Nucleotide-binding, Zinc |
Enzyme and pathway databases
BioCyci | MetaCyc:HS04742-MONOMER |
BRENDAi | 2.7.7.80 2681 2.8.1.11 2681 |
Reactomei | R-HSA-947581 Molybdenum cofactor biosynthesis |
UniPathwayi | UPA00344 UPA00988 |
Names & Taxonomyi
Protein namesi | Recommended name: Adenylyltransferase and sulfurtransferase MOCS3UniRule annotationAlternative 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 | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000124217.4 |
HGNCi | HGNC:15765 MOCS3 |
MIMi | 609277 gene |
neXtProti | NX_O95396 |
Subcellular locationi
Other locations
- Cytoplasm UniRule annotation1 Publication
Keywords - Cellular componenti
CytoplasmPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 239 | C → A: Impairs sulfurtransferase activity. 1 Publication | 1 | |
Mutagenesisi | 316 | C → A: Does not affect sulfurtransferase activity. 1 Publication | 1 | |
Mutagenesisi | 324 | C → A: Does not affect sulfurtransferase activity. 1 Publication | 1 | |
Mutagenesisi | 365 | C → A: Does not affect sulfurtransferase activity. 1 Publication | 1 | |
Mutagenesisi | 412 | C → A: Abolishes sulfurtransferase activity. 1 Publication | 1 | |
Mutagenesisi | 413 | K → R: Does not affect sulfurtransferase specificity and activity. 1 Publication | 1 | |
Mutagenesisi | 414 | L → K: Does not affect sulfurtransferase specificity and activity. 1 Publication | 1 | |
Mutagenesisi | 415 | G → A: Does not affect sulfurtransferase specificity and activity. 1 Publication | 1 | |
Mutagenesisi | 416 | N → V: Does not affect sulfurtransferase specificity and activity. 1 Publication | 1 | |
Mutagenesisi | 417 | D → R: Results in 470-fold increased activity. 1 Publication | 1 | |
Mutagenesisi | 417 | D → T: Results in 90-fold increased activity. 1 Publication | 1 | |
Mutagenesisi | 458 | P → G: Does not affect sulfurtransferase specificity and activity. 1 Publication | 1 | |
Mutagenesisi | 460 | Y → A: Does not affect sulfurtransferase specificity and activity. 1 Publication | 1 |
Organism-specific databases
OpenTargetsi | ENSG00000124217 |
PharmGKBi | PA30904 |
Polymorphism and mutation databases
BioMutai | MOCS3 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000120583 | 1 – 460 | Adenylyltransferase and sulfurtransferase MOCS3Add BLAST | 460 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Disulfide bondi | 316 ↔ 324 | 1 Publication |
Keywords - PTMi
Disulfide bondProteomic databases
EPDi | O95396 |
jPOSTi | O95396 |
MaxQBi | O95396 |
PaxDbi | O95396 |
PeptideAtlasi | O95396 |
PRIDEi | O95396 |
ProteomicsDBi | 50847 |
PTM databases
iPTMneti | O95396 |
PhosphoSitePlusi | O95396 |
Expressioni
Gene expression databases
Bgeei | ENSG00000124217 Expressed in 135 organ(s), highest expression level in sperm |
Genevisiblei | O95396 HS |
Interactioni
Subunit structurei
Interacts with NFS1.UniRule annotation1 Publication
Binary interactionsi
With | Entry | #Exp. | IntAct | Notes |
---|---|---|---|---|
URM1 | Q9BTM9 | 4 | EBI-373206,EBI-714589 |
Protein-protein interaction databases
BioGridi | 118127, 22 interactors |
DIPi | DIP-31168N |
IntActi | O95396, 2 interactors |
STRINGi | 9606.ENSP00000244051 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3I2V | X-ray | 1.25 | A | 335-460 | [»] | |
ProteinModelPortali | O95396 | |||||
SMRi | O95396 | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Miscellaneous databases
EvolutionaryTracei | O95396 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 347 – 458 | RhodaneseUniRule annotationAdd BLAST | 112 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG2017 Eukaryota COG0476 LUCA COG0607 LUCA |
GeneTreei | ENSGT00940000160847 |
HOGENOMi | HOG000281219 |
HOVERGENi | HBG052491 |
InParanoidi | O95396 |
KOi | K11996 |
OMAi | MIYDALE |
OrthoDBi | 1445129at2759 |
PhylomeDBi | O95396 |
TreeFami | TF106103 |
Family and domain databases
Gene3Di | 3.40.250.10, 1 hit |
HAMAPi | MF_03049 MOCS3_Uba4, 1 hit |
InterProi | View protein in InterPro IPR028885 MOCS3/Uba4 IPR001763 Rhodanese-like_dom IPR036873 Rhodanese-like_dom_sf IPR000594 ThiF_NAD_FAD-bd IPR035985 Ubiquitin-activating_enz |
Pfami | View protein in Pfam PF00581 Rhodanese, 1 hit PF00899 ThiF, 1 hit |
SMARTi | View protein in SMART SM00450 RHOD, 1 hit |
SUPFAMi | SSF69572 SSF69572, 1 hit |
PROSITEi | View protein in PROSITE PS50206 RHODANESE_3, 1 hit |
i Sequence
Sequence statusi: Complete.
O95396-1 [UniParc]FASTAAdd to basket
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
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_049349 | 429 | S → A. Corresponds to variant dbSNP:rs7269297Ensembl. | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF102544 mRNA Translation: AAC72412.1 AL034553 Genomic DNA No translation available. BC015939 mRNA Translation: AAH15939.1 |
CCDSi | CCDS13435.1 |
RefSeqi | NP_055299.1, NM_014484.4 |
UniGenei | Hs.159410 Hs.736268 |
Genome annotation databases
Ensembli | ENST00000244051; ENSP00000244051; ENSG00000124217 |
GeneIDi | 27304 |
KEGGi | hsa:27304 |
UCSCi | uc002xvy.3 human |
Keywords - Coding sequence diversityi
PolymorphismSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AF102544 mRNA Translation: AAC72412.1 AL034553 Genomic DNA No translation available. BC015939 mRNA Translation: AAH15939.1 |
CCDSi | CCDS13435.1 |
RefSeqi | NP_055299.1, NM_014484.4 |
UniGenei | Hs.159410 Hs.736268 |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
3I2V | X-ray | 1.25 | A | 335-460 | [»] | |
ProteinModelPortali | O95396 | |||||
SMRi | O95396 | |||||
ModBasei | Search... | |||||
MobiDBi | Search... |
Protein-protein interaction databases
BioGridi | 118127, 22 interactors |
DIPi | DIP-31168N |
IntActi | O95396, 2 interactors |
STRINGi | 9606.ENSP00000244051 |
PTM databases
iPTMneti | O95396 |
PhosphoSitePlusi | O95396 |
Polymorphism and mutation databases
BioMutai | MOCS3 |
Proteomic databases
EPDi | O95396 |
jPOSTi | O95396 |
MaxQBi | O95396 |
PaxDbi | O95396 |
PeptideAtlasi | O95396 |
PRIDEi | O95396 |
ProteomicsDBi | 50847 |
Protocols and materials databases
DNASUi | 27304 |
Structural Biology Knowledgebase | Search... |
Genome annotation databases
Ensembli | ENST00000244051; ENSP00000244051; ENSG00000124217 |
GeneIDi | 27304 |
KEGGi | hsa:27304 |
UCSCi | uc002xvy.3 human |
Organism-specific databases
CTDi | 27304 |
EuPathDBi | HostDB:ENSG00000124217.4 |
GeneCardsi | MOCS3 |
HGNCi | HGNC:15765 MOCS3 |
MIMi | 609277 gene |
neXtProti | NX_O95396 |
OpenTargetsi | ENSG00000124217 |
PharmGKBi | PA30904 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2017 Eukaryota COG0476 LUCA COG0607 LUCA |
GeneTreei | ENSGT00940000160847 |
HOGENOMi | HOG000281219 |
HOVERGENi | HBG052491 |
InParanoidi | O95396 |
KOi | K11996 |
OMAi | MIYDALE |
OrthoDBi | 1445129at2759 |
PhylomeDBi | O95396 |
TreeFami | TF106103 |
Enzyme and pathway databases
UniPathwayi | UPA00344 UPA00988 |
BioCyci | MetaCyc:HS04742-MONOMER |
BRENDAi | 2.7.7.80 2681 2.8.1.11 2681 |
Reactomei | R-HSA-947581 Molybdenum cofactor biosynthesis |
Miscellaneous databases
EvolutionaryTracei | O95396 |
GeneWikii | MOCS3 |
GenomeRNAii | 27304 |
PROi | PR:O95396 |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000124217 Expressed in 135 organ(s), highest expression level in sperm |
Genevisiblei | O95396 HS |
Family and domain databases
Gene3Di | 3.40.250.10, 1 hit |
HAMAPi | MF_03049 MOCS3_Uba4, 1 hit |
InterProi | View protein in InterPro IPR028885 MOCS3/Uba4 IPR001763 Rhodanese-like_dom IPR036873 Rhodanese-like_dom_sf IPR000594 ThiF_NAD_FAD-bd IPR035985 Ubiquitin-activating_enz |
Pfami | View protein in Pfam PF00581 Rhodanese, 1 hit PF00899 ThiF, 1 hit |
SMARTi | View protein in SMART SM00450 RHOD, 1 hit |
SUPFAMi | SSF69572 SSF69572, 1 hit |
PROSITEi | View protein in PROSITE PS50206 RHODANESE_3, 1 hit |
ProtoNeti | Search... |
Entry informationi
Entry namei | MOCS3_HUMAN | |
Accessioni | O95396Primary (citable) accession number: O95396 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | July 26, 2002 |
Last sequence update: | May 1, 1999 | |
Last modified: | February 13, 2019 | |
This is version 166 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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, Reference proteomeDocuments
- SIMILARITY comments
Index of protein domains and families - Human chromosome 20
Human chromosome 20: entries, gene names and cross-references to MIM - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - Human entries with polymorphisms or disease mutations
List of human entries with polymorphisms or disease mutations - Human polymorphisms and disease mutations
Index of human polymorphisms and disease mutations - PATHWAY comments
Index of metabolic and biosynthesis pathways