UniProt functional annotation for P25325



	UniProt functional annotation for P25325

UniProt code: P25325.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Transfer of a sulfur ion to cyanide or to other thiol compounds. Also has weak rhodanese activity. Detoxifies cyanide and is required for thiosulfate biosynthesis. Acts as an antioxidant. In combination with cysteine aminotransferase (CAT), contributes to the catabolism of cysteine and is an important producer of hydrogen sulfide in the brain, retina and vascular endothelial cells. Hydrogen sulfide H(2)S is an important synaptic modulator, signaling molecule, smooth muscle contractor and neuroprotectant. Its production by the 3MST/CAT pathway is regulated by calcium ions. {ECO:0000250|UniProtKB:P97532}.

Catalytic activity: Reaction=2-oxo-3-sulfanylpropanoate + [thioredoxin]-dithiol = [thioredoxin]-disulfide + H(+) + hydrogen sulfide + pyruvate; Xref=Rhea:RHEA:21740, Rhea:RHEA-COMP:10698, Rhea:RHEA-COMP:10700, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, ChEBI:CHEBI:29919, ChEBI:CHEBI:29950, ChEBI:CHEBI:50058, ChEBI:CHEBI:57678; EC=2.8.1.2; Evidence={ECO:0000250|UniProtKB:P97532};

Activity regulation: By oxidative stress, and thioredoxin. Under oxidative stress conditions, the catalytic cysteine site is converted to a sulfenate which inhibits the MPST enzyme activity. Reduced thioredoxin cleaves an intersubunit disulfide bond to turn on the redox switch and reactivate the enzyme. {ECO:0000250|UniProtKB:P97532}.

Subunit: Monomer (active form). Homodimer; disulfide-linked (inactive form). {ECO:0000250|UniProtKB:P97532}.

Subcellular location: Cytoplasm {ECO:0000250|UniProtKB:P97532}. Mitochondrion {ECO:0000250|UniProtKB:P97532}. Cell junction, synapse, synaptosome {ECO:0000250|UniProtKB:Q99J99}.

Domain: Contains two rhodanese domains with different primary structures but with near identical secondary structure conformations suggesting a common evolutionary origin. Only the C-terminal rhodanese domain contains the catalytic cysteine residue (By similarity). {ECO:0000250}.

Disease: Note=Aberrant MPST activity is found in a few cases of mercaptolactate-cysteine disulfiduria (MCDU) characterized by the appearance of large quantaties of the sulfur-containing amino acid, beta-mercaptolactate-cysteine disulfide, in the urine (PubMed:4973015, PubMed:4690911 and PubMed:6945862). Some cases have associated mental retardation (PubMed:4973015 and PubMed:6945862).

Miscellaneous: Thioredoxin (Trx) or dihydrolipoic acid (DHLA) are required to release hydrogen sulfide from the persulfide intermediate. {ECO:0000250|UniProtKB:Q99J99}.

Sequence caution: Sequence=AAH16737.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=CAG30409.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Transfer of a sulfur ion to cyanide or to other thiol compounds. Also has weak rhodanese activity. Detoxifies cyanide and is required for thiosulfate biosynthesis. Acts as an antioxidant. In combination with cysteine aminotransferase (CAT), contributes to the catabolism of cysteine and is an important producer of hydrogen sulfide in the brain, retina and vascular endothelial cells. Hydrogen sulfide H(2)S is an important synaptic modulator, signaling molecule, smooth muscle contractor and neuroprotectant. Its production by the 3MST/CAT pathway is regulated by calcium ions. {ECO:0000250\|UniProtKB:P97532}.


Catalytic activity:		Reaction=2-oxo-3-sulfanylpropanoate + [thioredoxin]-dithiol = [thioredoxin]-disulfide + H(+) + hydrogen sulfide + pyruvate; Xref=Rhea:RHEA:21740, Rhea:RHEA-COMP:10698, Rhea:RHEA-COMP:10700, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, ChEBI:CHEBI:29919, ChEBI:CHEBI:29950, ChEBI:CHEBI:50058, ChEBI:CHEBI:57678; EC=2.8.1.2; Evidence={ECO:0000250\|UniProtKB:P97532};
Activity regulation:		By oxidative stress, and thioredoxin. Under oxidative stress conditions, the catalytic cysteine site is converted to a sulfenate which inhibits the MPST enzyme activity. Reduced thioredoxin cleaves an intersubunit disulfide bond to turn on the redox switch and reactivate the enzyme. {ECO:0000250\|UniProtKB:P97532}.
Subunit:		Monomer (active form). Homodimer; disulfide-linked (inactive form). {ECO:0000250\|UniProtKB:P97532}.
Subcellular location:		Cytoplasm {ECO:0000250\|UniProtKB:P97532}. Mitochondrion {ECO:0000250\|UniProtKB:P97532}. Cell junction, synapse, synaptosome {ECO:0000250\|UniProtKB:Q99J99}.
Domain:		Contains two rhodanese domains with different primary structures but with near identical secondary structure conformations suggesting a common evolutionary origin. Only the C-terminal rhodanese domain contains the catalytic cysteine residue (By similarity). {ECO:0000250}.
Disease:		Note=Aberrant MPST activity is found in a few cases of mercaptolactate-cysteine disulfiduria (MCDU) characterized by the appearance of large quantaties of the sulfur-containing amino acid, beta-mercaptolactate-cysteine disulfide, in the urine (PubMed:4973015, PubMed:4690911 and PubMed:6945862). Some cases have associated mental retardation (PubMed:4973015 and PubMed:6945862).
Miscellaneous:		Thioredoxin (Trx) or dihydrolipoic acid (DHLA) are required to release hydrogen sulfide from the persulfide intermediate. {ECO:0000250\|UniProtKB:Q99J99}.
Sequence caution:		Sequence=AAH16737.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305}; Sequence=CAG30409.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};