TDH_MOUSE
ID TDH_MOUSE Reviewed; 373 AA.
AC Q8K3F7; Q6PD91; Q9JLU3;
DT 21-AUG-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 03-AUG-2022, entry version 128.
DE RecName: Full=L-threonine 3-dehydrogenase, mitochondrial {ECO:0000305};
DE EC=1.1.1.103 {ECO:0000269|PubMed:26492815};
DE Flags: Precursor;
GN Name=Tdh {ECO:0000312|MGI:MGI:1926231};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1] {ECO:0000312|EMBL:AAM51557.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=BALB/cJ {ECO:0000312|EMBL:AAM51557.1};
RC TISSUE=Liver {ECO:0000312|EMBL:AAM51557.1};
RX PubMed=12097150; DOI=10.1186/1471-2091-3-19;
RA Edgar A.J.;
RT "Molecular cloning and tissue distribution of mammalian L-threonine 3-
RT dehydrogenases.";
RL BMC Biochem. 3:19-19(2002).
RN [2] {ECO:0000312|EMBL:BAC36870.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:BAC36870.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:BAC36870.1};
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3] {ECO:0000312|EMBL:AAH58860.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J {ECO:0000312|EMBL:AAH58860.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:AAH58860.1};
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 [4] {ECO:0007744|PDB:4YR9, ECO:0007744|PDB:4YRA, ECO:0007744|PDB:4YRB}
RP X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 47-373 OF WILD-TYPE AND VARIANT
RP LYS-180 IN COMPLEX WITH NAD, FUNCTION, CATALYTIC ACTIVITY, PATHWAY,
RP SUBUNIT, BIOPHYSICOCHEMICAL PROPERTIES, ACTIVE SITE, AND MUTAGENESIS OF
RP SER-133; ARG-180; THR-237 AND MET-333.
RX PubMed=26492815; DOI=10.1016/j.jsb.2015.10.014;
RA He C., Huang X., Liu Y., Li F., Yang Y., Tao H., Han C., Zhao C., Xiao Y.,
RA Shi Y.;
RT "Structural insights on mouse L-threonine dehydrogenase: A regulatory role
RT of Arg180 in catalysis.";
RL J. Struct. Biol. 192:510-518(2015).
CC -!- FUNCTION: Catalyzes the NAD(+)-dependent oxidation of L-threonine to 2-
CC amino-3-ketobutyrate, mediating L-threonine catabolism.
CC {ECO:0000269|PubMed:26492815}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-threonine + NAD(+) = (2S)-2-amino-3-oxobutanoate + H(+) +
CC NADH; Xref=Rhea:RHEA:13161, ChEBI:CHEBI:15378, ChEBI:CHEBI:57540,
CC ChEBI:CHEBI:57926, ChEBI:CHEBI:57945, ChEBI:CHEBI:78948;
CC EC=1.1.1.103; Evidence={ECO:0000269|PubMed:26492815};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=72.4 mM for L-threonine {ECO:0000269|PubMed:26492815};
CC KM=1.67 mM for NAD(+) {ECO:0000269|PubMed:26492815};
CC -!- PATHWAY: Amino-acid degradation; L-threonine degradation via oxydo-
CC reductase pathway; glycine from L-threonine: step 1/2.
CC {ECO:0000305|PubMed:26492815}.
CC -!- SUBUNIT: Homodimer. {ECO:0000305|PubMed:26492815}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000250|UniProtKB:Q8MIR0}.
CC -!- SIMILARITY: Belongs to the NAD(P)-dependent epimerase/dehydratase
CC family. {ECO:0000305}.
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DR EMBL; AF134346; AAF61395.2; -; mRNA.
DR EMBL; AY116662; AAM51557.1; -; mRNA.
DR EMBL; AK077571; BAC36870.1; -; mRNA.
DR EMBL; BC058860; AAH58860.1; -; mRNA.
DR CCDS; CCDS27202.1; -.
DR RefSeq; NP_067455.5; NM_021480.5.
DR PDB; 4YR9; X-ray; 2.80 A; A/B/C/D/E/F=47-373.
DR PDB; 4YRA; X-ray; 2.65 A; A/B/C/D/E/F/G/H/I/J/K/L=47-373.
DR PDB; 4YRB; X-ray; 3.25 A; A/B/C/D/E/F=47-373.
DR PDBsum; 4YR9; -.
DR PDBsum; 4YRA; -.
DR PDBsum; 4YRB; -.
DR AlphaFoldDB; Q8K3F7; -.
DR SMR; Q8K3F7; -.
DR BioGRID; 208451; 4.
DR STRING; 10090.ENSMUSP00000022522; -.
DR iPTMnet; Q8K3F7; -.
DR PhosphoSitePlus; Q8K3F7; -.
DR PaxDb; Q8K3F7; -.
DR PeptideAtlas; Q8K3F7; -.
DR PRIDE; Q8K3F7; -.
DR ProteomicsDB; 262738; -.
DR DNASU; 58865; -.
DR Ensembl; ENSMUST00000022522; ENSMUSP00000022522; ENSMUSG00000021953.
DR GeneID; 58865; -.
DR KEGG; mmu:58865; -.
DR UCSC; uc007uhs.1; mouse.
DR CTD; 157739; -.
DR MGI; MGI:1926231; Tdh.
DR VEuPathDB; HostDB:ENSMUSG00000021953; -.
DR eggNOG; KOG2774; Eukaryota.
DR GeneTree; ENSGT00390000014037; -.
DR HOGENOM; CLU_007383_19_1_1; -.
DR InParanoid; Q8K3F7; -.
DR OMA; HWHASPR; -.
DR OrthoDB; 1327602at2759; -.
DR PhylomeDB; Q8K3F7; -.
DR TreeFam; TF314544; -.
DR BRENDA; 1.1.1.103; 3474.
DR UniPathway; UPA00046; UER00505.
DR BioGRID-ORCS; 58865; 2 hits in 70 CRISPR screens.
DR ChiTaRS; Tdh; mouse.
DR PRO; PR:Q8K3F7; -.
DR Proteomes; UP000000589; Chromosome 14.
DR RNAct; Q8K3F7; protein.
DR Bgee; ENSMUSG00000021953; Expressed in yolk sac and 36 other tissues.
DR ExpressionAtlas; Q8K3F7; baseline and differential.
DR Genevisible; Q8K3F7; MM.
DR GO; GO:0005739; C:mitochondrion; HDA:MGI.
DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB.
DR GO; GO:0008743; F:L-threonine 3-dehydrogenase activity; IDA:UniProtKB.
DR GO; GO:0019518; P:L-threonine catabolic process to glycine; IEA:UniProtKB-UniPathway.
DR GO; GO:0006567; P:threonine catabolic process; IDA:UniProtKB.
DR InterPro; IPR001509; Epimerase_deHydtase.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF01370; Epimerase; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Mitochondrion; NAD; Oxidoreductase; Reference proteome;
KW Transit peptide.
FT TRANSIT 1..?
FT /note="Mitochondrion"
FT /evidence="ECO:0000255"
FT CHAIN ?..373
FT /note="L-threonine 3-dehydrogenase, mitochondrial"
FT /id="PRO_0000298784"
FT ACT_SITE 195
FT /note="Proton donor/acceptor"
FT /evidence="ECO:0000305|PubMed:26492815"
FT BINDING 62..67
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:26492815,
FT ECO:0007744|PDB:4YR9, ECO:0007744|PDB:4YRA,
FT ECO:0007744|PDB:4YRB"
FT BINDING 88..90
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:26492815,
FT ECO:0007744|PDB:4YR9, ECO:0007744|PDB:4YRA,
FT ECO:0007744|PDB:4YRB"
FT BINDING 106..107
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:26492815,
FT ECO:0007744|PDB:4YR9, ECO:0007744|PDB:4YRA,
FT ECO:0007744|PDB:4YRB"
FT BINDING 195
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:26492815,
FT ECO:0007744|PDB:4YR9, ECO:0007744|PDB:4YRA,
FT ECO:0007744|PDB:4YRB"
FT BINDING 199
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:26492815,
FT ECO:0007744|PDB:4YR9, ECO:0007744|PDB:4YRA,
FT ECO:0007744|PDB:4YRB"
FT BINDING 225
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:26492815,
FT ECO:0007744|PDB:4YR9, ECO:0007744|PDB:4YRA,
FT ECO:0007744|PDB:4YRB"
FT MUTAGEN 133
FT /note="S->A: Decreased L-threonine 3-dehydrogenase
FT activity."
FT /evidence="ECO:0000269|PubMed:26492815"
FT MUTAGEN 180
FT /note="R->K: Decreased L-threonine 3-dehydrogenase
FT activity. No effect on protein NAD(+)-binding. No gross
FT effect on protein folding. No effect on protein stability."
FT /evidence="ECO:0000269|PubMed:26492815"
FT MUTAGEN 237
FT /note="T->A: Decreased L-threonine 3-dehydrogenase
FT activity."
FT /evidence="ECO:0000269|PubMed:26492815"
FT MUTAGEN 333
FT /note="M->A: Decreased L-threonine 3-dehydrogenase
FT activity."
FT /evidence="ECO:0000269|PubMed:26492815"
FT MUTAGEN 333
FT /note="M->E: Decreased L-threonine 3-dehydrogenase
FT activity. Decreased affinity for L-threonine."
FT /evidence="ECO:0000269|PubMed:26492815"
FT CONFLICT 82
FT /note="D -> N (in Ref. 3; AAH58860)"
FT /evidence="ECO:0000305"
FT CONFLICT 214
FT /note="G -> V (in Ref. 1; AAF61395)"
FT /evidence="ECO:0000305"
FT CONFLICT 232
FT /note="P -> R (in Ref. 1; AAF61395)"
FT /evidence="ECO:0000305"
FT CONFLICT 318
FT /note="Y -> H (in Ref. 3; AAH58860)"
FT /evidence="ECO:0000305"
FT CONFLICT 361
FT /note="N -> S (in Ref. 1; AAF61395)"
FT /evidence="ECO:0000305"
FT STRAND 58..61
FT /evidence="ECO:0007829|PDB:4YRA"
FT TURN 62..64
FT /evidence="ECO:0007829|PDB:4YRA"
FT HELIX 66..79
FT /evidence="ECO:0007829|PDB:4YRA"
FT HELIX 81..83
FT /evidence="ECO:0007829|PDB:4YRA"
FT STRAND 84..88
FT /evidence="ECO:0007829|PDB:4YRA"
FT HELIX 94..97
FT /evidence="ECO:0007829|PDB:4YR9"
FT STRAND 102..104
FT /evidence="ECO:0007829|PDB:4YRA"
FT HELIX 110..119
FT /evidence="ECO:0007829|PDB:4YRA"
FT STRAND 124..127
FT /evidence="ECO:0007829|PDB:4YRA"
FT HELIX 133..138
FT /evidence="ECO:0007829|PDB:4YR9"
FT HELIX 146..160
FT /evidence="ECO:0007829|PDB:4YRA"
FT STRAND 164..166
FT /evidence="ECO:0007829|PDB:4YRA"
FT HELIX 171..173
FT /evidence="ECO:0007829|PDB:4YRA"
FT STRAND 181..183
FT /evidence="ECO:0007829|PDB:4YRA"
FT STRAND 185..187
FT /evidence="ECO:0007829|PDB:4YR9"
FT HELIX 194..212
FT /evidence="ECO:0007829|PDB:4YRA"
FT STRAND 217..222
FT /evidence="ECO:0007829|PDB:4YRA"
FT STRAND 224..226
FT /evidence="ECO:0007829|PDB:4YRA"
FT HELIX 236..238
FT /evidence="ECO:0007829|PDB:4YR9"
FT HELIX 239..248
FT /evidence="ECO:0007829|PDB:4YRA"
FT STRAND 252..257
FT /evidence="ECO:0007829|PDB:4YRA"
FT STRAND 263..267
FT /evidence="ECO:0007829|PDB:4YRA"
FT HELIX 268..280
FT /evidence="ECO:0007829|PDB:4YRA"
FT HELIX 283..285
FT /evidence="ECO:0007829|PDB:4YR9"
FT STRAND 289..292
FT /evidence="ECO:0007829|PDB:4YRA"
FT STRAND 295..298
FT /evidence="ECO:0007829|PDB:4YRA"
FT HELIX 300..308
FT /evidence="ECO:0007829|PDB:4YRA"
FT STRAND 315..318
FT /evidence="ECO:0007829|PDB:4YRA"
FT HELIX 322..330
FT /evidence="ECO:0007829|PDB:4YRA"
FT HELIX 338..344
FT /evidence="ECO:0007829|PDB:4YRA"
FT HELIX 352..362
FT /evidence="ECO:0007829|PDB:4YRA"
SQ SEQUENCE 373 AA; 41462 MW; 6A416A079A7EC381 CRC64;
MLFLGMLKQV VNGTAQSKAS SCRKLVLPLK FLGTSQHRIP ADANFHSTSI SEAEPPRVLI
TGGLGQLGVG LANLLRKRFG KDNVILSDIR KPPAHVFHSG PFVYANILDY KSLREIVVNH
RISWLFHYSA LLSAVGEANV SLARDVNITG LHNVLDVAAE YNVRLFVPST IGAFGPTSPR
NPAPDLCIQR PRTIYGVSKV HTELMGEYYY YRYGLDFRCL RYPGIISADS QPGGGTTDYA
VQIFHAAAKN GTFECNLEAG TRLPMMYISD CLRATLEVME APAERLSMRT YNISAMSFTP
EELAQALRKH APDFQITYCV DPLRQAIAES WPMILDDSNA RKDWGWKHDF DLPELVATML
NFHGVSTRVA QVN
