THTM_RAT
ID THTM_RAT Reviewed; 297 AA.
AC P97532;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 146.
DE RecName: Full=3-mercaptopyruvate sulfurtransferase;
DE Short=MST;
DE EC=2.8.1.2 {ECO:0000269|PubMed:8910318, ECO:0000269|PubMed:9749958};
GN Name=Mpst;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 9-77 AND 147-285, ACTIVE
RP SITE, MUTAGENESIS OF ARG-188; ARG-197; CYS-248 AND SER-250, FUNCTION, AND
RP CATALYTIC ACTIVITY.
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=8910318; DOI=10.1074/jbc.271.44.27395;
RA Nagahara N., Nishino T.;
RT "Role of amino acid residues in the active site of rat liver
RT mercaptopyruvate sulfurtransferase. cDNA cloning, overexpression, and site-
RT directed mutagenesis.";
RL J. Biol. Chem. 271:27395-27401(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP PROTEIN SEQUENCE OF 9-77 AND 147-285, AND CHARACTERIZATION.
RC STRAIN=Wistar; TISSUE=Liver;
RX PubMed=7608189; DOI=10.1074/jbc.270.27.16230;
RA Nagahara N., Okazaki T., Nishino T.;
RT "Cytosolic mercaptopyruvate sulfurtransferase is evolutionarily related to
RT mitochondrial rhodanese. Striking similarity in active site amino acid
RT sequence and the increase in the mercaptopyruvate sulfurtransferase
RT activity of rhodanese by site-directed mutagenesis.";
RL J. Biol. Chem. 270:16230-16235(1995).
RN [4]
RP PROTEIN SEQUENCE OF 53-64 AND 119-164, AND IDENTIFICATION BY MASS
RP SPECTROMETRY.
RC STRAIN=Sprague-Dawley; TISSUE=Spinal cord;
RA Lubec G., Afjehi-Sadat L.;
RL Submitted (NOV-2006) to UniProtKB.
RN [5]
RP SUBCELLULAR LOCATION, TISSUE SPECIFICITY, FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=9749958; DOI=10.1007/s004180050286;
RA Nagahara N., Ito T., Kitamura H., Nishino T.;
RT "Tissue and subcellular distribution of mercaptopyruvate sulfurtransferase
RT in the rat: confocal laser fluorescence and immunoelectron microscopic
RT studies combined with biochemical analysis.";
RL Histochem. Cell Biol. 110:243-250(1998).
RN [6]
RP FUNCTION, ACTIVITY REGULATION, IDENTIFICATION BY MASS SPECTROMETRY, AND
RP MUTAGENESIS OF CYS-65; CYS-155; CYS-248; CYS-255 AND CYS-264.
RX PubMed=16107337; DOI=10.1074/jbc.m505643200;
RA Nagahara N., Katayama A.;
RT "Post-translational regulation of mercaptopyruvate sulfurtransferase via a
RT low redox potential cysteine-sulfenate in the maintenance of redox
RT homeostasis.";
RL J. Biol. Chem. 280:34569-34576(2005).
RN [7]
RP ACTIVITY REGULATION, AND SUBUNIT.
RX PubMed=17130129; DOI=10.1074/jbc.m605931200;
RA Nagahara N., Yoshii T., Abe Y., Matsumura T.;
RT "Thioredoxin-dependent enzymatic activation of mercaptopyruvate
RT sulfurtransferase. An intersubunit disulfide bond serves as a redox switch
RT for activation.";
RL J. Biol. Chem. 282:1561-1569(2007).
RN [8]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=19605461; DOI=10.1093/jb/mvp111;
RA Shibuya N., Mikami Y., Kimura Y., Nagahara N., Kimura H.;
RT "Vascular endothelium expresses 3-mercaptopyruvate sulfurtransferase and
RT produces hydrogen sulfide.";
RL J. Biochem. 146:623-626(2009).
CC -!- FUNCTION: Transfer of a sulfur ion to cyanide or to other thiol
CC compounds. Also has weak rhodanese activity. Detoxifies cyanide and is
CC required for thiosulfate biosynthesis. Acts as an antioxidant. In
CC combination with cysteine aminotransferase (CAT), contributes to the
CC catabolism of cysteine and is an important producer of hydrogen sulfide
CC in the brain, retina and vascular endothelial cells. Hydrogen sulfide
CC H(2)S is an important synaptic modulator, signaling molecule, smooth
CC muscle contractor and neuroprotectant. Its production by the 3MST/CAT
CC pathway is regulated by calcium ions. {ECO:0000269|PubMed:16107337,
CC ECO:0000269|PubMed:19605461, ECO:0000269|PubMed:8910318,
CC ECO:0000269|PubMed:9749958}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2-oxo-3-sulfanylpropanoate + [thioredoxin]-dithiol =
CC [thioredoxin]-disulfide + H(+) + hydrogen sulfide + pyruvate;
CC Xref=Rhea:RHEA:21740, Rhea:RHEA-COMP:10698, Rhea:RHEA-COMP:10700,
CC ChEBI:CHEBI:15361, ChEBI:CHEBI:15378, ChEBI:CHEBI:29919,
CC ChEBI:CHEBI:29950, ChEBI:CHEBI:50058, ChEBI:CHEBI:57678; EC=2.8.1.2;
CC Evidence={ECO:0000269|PubMed:8910318, ECO:0000269|PubMed:9749958};
CC -!- ACTIVITY REGULATION: By oxidative stress, and thioredoxin. Under
CC oxidative stress conditions, the catalytic cysteine site is converted
CC to a sulfenate which inhibits the MPST enzyme activity. Reduced
CC thioredoxin cleaves an intersubunit disulfide bond to turn on the redox
CC switch and reactivate the enzyme. Inhibited by different oxidants,
CC hydrogen peroxide and tetrathionate. {ECO:0000269|PubMed:16107337,
CC ECO:0000269|PubMed:17130129}.
CC -!- SUBUNIT: Monomer (active form). Homodimer; disulfide-linked (inactive
CC form). {ECO:0000269|PubMed:17130129}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:9749958}.
CC Mitochondrion {ECO:0000269|PubMed:9749958}. Synapse, synaptosome
CC {ECO:0000250|UniProtKB:Q99J99}.
CC -!- TISSUE SPECIFICITY: Expressed in liver, heart, kidney and brain.
CC Localizes to tubular epithelium in the kidney, pericentral hepatocytes
CC in the liver, cardiac cells in the heart and neuroglial cells in the
CC brain. Also expressed in vascular endothelium of the thoracic aorta.
CC Weak expression in lung and thymus. {ECO:0000269|PubMed:19605461,
CC ECO:0000269|PubMed:9749958}.
CC -!- DOMAIN: Contains two rhodanese domains with different primary
CC structures but with near identical secondary structure conformations
CC suggesting a common evolutionary origin. Only the C-terminal rhodanese
CC domain contains the catalytic cysteine residue (By similarity).
CC {ECO:0000250}.
CC -!- PTM: The N-terminus is blocked.
CC -!- MISCELLANEOUS: Thioredoxin (Trx) or dihydrolipoic acid (DHLA) are
CC required to release hydrogen sulfide from the persulfide intermediate.
CC {ECO:0000250|UniProtKB:Q99J99}.
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DR EMBL; D50564; BAA09127.1; -; mRNA.
DR EMBL; BC086575; AAH86575.1; -; mRNA.
DR PIR; A57483; A57483.
DR RefSeq; NP_620198.1; NM_138843.1.
DR AlphaFoldDB; P97532; -.
DR SMR; P97532; -.
DR STRING; 10116.ENSRNOP00000000201; -.
DR iPTMnet; P97532; -.
DR PhosphoSitePlus; P97532; -.
DR SwissPalm; P97532; -.
DR World-2DPAGE; 0004:P97532; -.
DR jPOST; P97532; -.
DR PaxDb; P97532; -.
DR PRIDE; P97532; -.
DR Ensembl; ENSRNOT00000000201; ENSRNOP00000000201; ENSRNOG00000000185.
DR GeneID; 192172; -.
DR KEGG; rno:192172; -.
DR UCSC; RGD:620065; rat.
DR CTD; 4357; -.
DR RGD; 620065; Mpst.
DR eggNOG; KOG1529; Eukaryota.
DR GeneTree; ENSGT00510000046773; -.
DR HOGENOM; CLU_031618_3_1_1; -.
DR InParanoid; P97532; -.
DR OMA; QRPGHVP; -.
DR OrthoDB; 1553525at2759; -.
DR PhylomeDB; P97532; -.
DR TreeFam; TF315133; -.
DR BioCyc; MetaCyc:MON-12473; -.
DR BRENDA; 2.8.1.2; 5301.
DR Reactome; R-RNO-1614558; Degradation of cysteine and homocysteine.
DR SABIO-RK; P97532; -.
DR PRO; PR:P97532; -.
DR Proteomes; UP000002494; Chromosome 7.
DR Bgee; ENSRNOG00000000185; Expressed in adult mammalian kidney and 19 other tissues.
DR Genevisible; P97532; RN.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR GO; GO:0043005; C:neuron projection; ISS:UniProtKB.
DR GO; GO:0045202; C:synapse; IEA:UniProtKB-SubCell.
DR GO; GO:0016784; F:3-mercaptopyruvate sulfurtransferase activity; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; IDA:RGD.
DR GO; GO:0004792; F:thiosulfate sulfurtransferase activity; IDA:RGD.
DR GO; GO:0070814; P:hydrogen sulfide biosynthetic process; ISS:UniProtKB.
DR GO; GO:0001822; P:kidney development; IDA:RGD.
DR GO; GO:0001889; P:liver development; IDA:RGD.
DR GO; GO:0021510; P:spinal cord development; IEP:RGD.
DR GO; GO:0019346; P:transsulfuration; IDA:RGD.
DR Gene3D; 3.40.250.10; -; 2.
DR InterPro; IPR001763; Rhodanese-like_dom.
DR InterPro; IPR036873; Rhodanese-like_dom_sf.
DR InterPro; IPR001307; Thiosulphate_STrfase_CS.
DR InterPro; IPR045078; TST/MPST-like.
DR PANTHER; PTHR11364; PTHR11364; 1.
DR Pfam; PF00581; Rhodanese; 2.
DR SMART; SM00450; RHOD; 2.
DR SUPFAM; SSF52821; SSF52821; 2.
DR PROSITE; PS00380; RHODANESE_1; 1.
DR PROSITE; PS00683; RHODANESE_2; 1.
DR PROSITE; PS50206; RHODANESE_3; 2.
PE 1: Evidence at protein level;
KW Acetylation; Cytoplasm; Direct protein sequencing; Disulfide bond;
KW Mitochondrion; Phosphoprotein; Redox-active center; Reference proteome;
KW Repeat; Synapse; Synaptosome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P25325"
FT CHAIN 2..297
FT /note="3-mercaptopyruvate sulfurtransferase"
FT /id="PRO_0000139400"
FT DOMAIN 25..144
FT /note="Rhodanese 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00173"
FT DOMAIN 174..288
FT /note="Rhodanese 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00173"
FT REGION 145..160
FT /note="Hinge"
FT ACT_SITE 248
FT /note="Cysteine persulfide intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00173,
FT ECO:0000269|PubMed:8910318"
FT BINDING 188
FT /ligand="substrate"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P25325"
FT MOD_RES 35
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P25325"
FT MOD_RES 40
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99J99"
FT MOD_RES 40
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:Q99J99"
FT MOD_RES 146
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99J99"
FT MOD_RES 164
FT /note="N6-succinyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q99J99"
FT DISULFID 155
FT /note="Interchain (with C-155 or C-264); redox-active"
FT /evidence="ECO:0000250"
FT DISULFID 264
FT /note="Interchain (with C-155 or C-264); redox-active"
FT /evidence="ECO:0000250"
FT MUTAGEN 65
FT /note="C->S: No effect on redox potential."
FT /evidence="ECO:0000269|PubMed:16107337"
FT MUTAGEN 155
FT /note="C->S: No effect on redox potential."
FT /evidence="ECO:0000269|PubMed:16107337"
FT MUTAGEN 188
FT /note="R->G: Large decrease in MST activity; some decrease
FT in rhodanese activity."
FT /evidence="ECO:0000269|PubMed:8910318"
FT MUTAGEN 197
FT /note="R->G: Decreased MST activity; increased rhodanese
FT activity."
FT /evidence="ECO:0000269|PubMed:8910318"
FT MUTAGEN 248
FT /note="C->S: Loss of both enzyme activities. Greatly
FT reduced redox potential."
FT /evidence="ECO:0000269|PubMed:16107337,
FT ECO:0000269|PubMed:8910318"
FT MUTAGEN 249
FT /note="G->R: Decreased MST activity; increased rhodanese
FT activity."
FT MUTAGEN 250
FT /note="S->A: Slight decrease in MST activity."
FT /evidence="ECO:0000269|PubMed:8910318"
FT MUTAGEN 250
FT /note="S->K: Slight decrease in MST activity; increased
FT rhodanese activity."
FT /evidence="ECO:0000269|PubMed:8910318"
FT MUTAGEN 255
FT /note="C->S: Little change in redox potential."
FT /evidence="ECO:0000269|PubMed:16107337"
FT MUTAGEN 264
FT /note="C->S: Greatly reduced redox potential."
FT /evidence="ECO:0000269|PubMed:16107337"
SQ SEQUENCE 297 AA; 32940 MW; 314E2B8EAFDEFB77 CRC64;
MAAPQLFRAL VSAQWVAEAL KSPRASQPLK LLDASWYLPK LGRDARREFE ERHIPGAAFF
DIDRCSDHTS PYDHMLPSAT HFADYAGSLG VSAATHVVIY DGSDQGLYSA PRVWWMFRAF
GHHSVSLLDG GFRYWLSQNL PISSGKSPSE PAEFCAQLDP SFIKTHEDIL ENLDARRFQV
VDARAAGRFQ GTQPEPRDGI EPGHIPGSVN IPFTEFLTSE GLEKSPEEIQ RLFQEKKVDL
SKPLVATCGS GVTACHVVLG AFLCGKPDVP VYDGSWVEWY MRAQPEHVIS QGRGKTL
