LDHA_RABIT
ID LDHA_RABIT Reviewed; 332 AA.
AC P13491;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=L-lactate dehydrogenase A chain;
DE Short=LDH-A;
DE EC=1.1.1.27 {ECO:0000250|UniProtKB:P00338};
DE AltName: Full=LDH muscle subunit;
DE Short=LDH-M;
GN Name=LDHA;
OS Oryctolagus cuniculus (Rabbit).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX NCBI_TaxID=9986;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=2917988; DOI=10.1016/s0021-9258(19)84964-5;
RA Sass C., Briand M., Benslimane S., Renaud M., Briand Y.;
RT "Characterization of rabbit lactate dehydrogenase-M and lactate
RT dehydrogenase-H cDNAs. Control of lactate dehydrogenase expression in
RT rabbit muscle.";
RL J. Biol. Chem. 264:4076-4081(1989).
RN [2]
RP X-RAY CRYSTALLOGRAPHY (2.38 ANGSTROMS) OF 2-332 IN COMPLEX WITH NADH AMD
RP INHIBITOR, SUBUNIT, ACTIVE SITE, SUBSTRATE-BINDING SITES, AND NAD-BINDING
RP SITES.
RX PubMed=19715328; DOI=10.1021/jp903579x;
RA Swiderek K., Panczakiewicz A., Bujacz A., Bujacz G., Paneth P.;
RT "Modeling of isotope effects on binding oxamate to lactic dehydrogenase.";
RL J. Phys. Chem. B 113:12782-12789(2009).
CC -!- FUNCTION: Interconverts simultaneously and stereospecifically pyruvate
CC and lactate with concomitant interconversion of NADH and NAD(+).
CC {ECO:0000250|UniProtKB:P00338}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=(S)-lactate + NAD(+) = H(+) + NADH + pyruvate;
CC Xref=Rhea:RHEA:23444, ChEBI:CHEBI:15361, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16651, ChEBI:CHEBI:57540, ChEBI:CHEBI:57945; EC=1.1.1.27;
CC Evidence={ECO:0000250|UniProtKB:P00338};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:23445;
CC Evidence={ECO:0000250|UniProtKB:P00338};
CC PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:23446;
CC Evidence={ECO:0000250|UniProtKB:P00338};
CC -!- PATHWAY: Fermentation; pyruvate fermentation to lactate; (S)-lactate
CC from pyruvate: step 1/1. {ECO:0000250|UniProtKB:P00338}.
CC -!- SUBUNIT: Homotetramer (PubMed:19715328). Interacts with PTEN upstream
CC reading frame protein MP31 (By similarity).
CC {ECO:0000250|UniProtKB:P00338, ECO:0000269|PubMed:19715328}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm.
CC -!- PTM: ISGylated. {ECO:0000250|UniProtKB:P00338}.
CC -!- SIMILARITY: Belongs to the LDH/MDH superfamily. LDH family.
CC {ECO:0000305}.
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DR EMBL; M22585; AAA31382.1; -; mRNA.
DR PIR; A32957; A32957.
DR RefSeq; NP_001075746.1; NM_001082277.1.
DR PDB; 3H3F; X-ray; 2.38 A; A/B/C/D/E/F/G/H=2-332.
DR PDB; 4I8X; X-ray; 2.23 A; A/B/C/D/E/F/G/H=2-332.
DR PDB; 4I9H; X-ray; 2.17 A; A/B/C/D/E/F/G/H=2-332.
DR PDB; 4I9N; X-ray; 2.35 A; A/B/C/D/E/F/G/H=2-332.
DR PDB; 4I9U; X-ray; 2.50 A; A/B/C/D/E/F/G/H=2-332.
DR PDB; 5KKC; X-ray; 1.86 A; A/B/C/D=2-332.
DR PDB; 5NQB; X-ray; 1.58 A; A/B/C/D=1-332.
DR PDB; 5NQQ; X-ray; 1.87 A; A/B/C/D=1-332.
DR PDB; 6P6U; X-ray; 2.42 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P=1-332.
DR PDBsum; 3H3F; -.
DR PDBsum; 4I8X; -.
DR PDBsum; 4I9H; -.
DR PDBsum; 4I9N; -.
DR PDBsum; 4I9U; -.
DR PDBsum; 5KKC; -.
DR PDBsum; 5NQB; -.
DR PDBsum; 5NQQ; -.
DR PDBsum; 6P6U; -.
DR AlphaFoldDB; P13491; -.
DR SMR; P13491; -.
DR IntAct; P13491; 1.
DR STRING; 9986.ENSOCUP00000021667; -.
DR ChEMBL; CHEMBL4523188; -.
DR GeneID; 100009107; -.
DR KEGG; ocu:100009107; -.
DR CTD; 3939; -.
DR eggNOG; KOG1495; Eukaryota.
DR InParanoid; P13491; -.
DR BRENDA; 1.1.1.27; 1749.
DR SABIO-RK; P13491; -.
DR UniPathway; UPA00554; UER00611.
DR EvolutionaryTrace; P13491; -.
DR Proteomes; UP000001811; Unplaced.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004459; F:L-lactate dehydrogenase activity; IEA:UniProtKB-EC.
DR GO; GO:0006089; P:lactate metabolic process; IEA:UniProt.
DR Gene3D; 3.90.110.10; -; 1.
DR HAMAP; MF_00488; Lactate_dehydrog; 1.
DR InterPro; IPR001557; L-lactate/malate_DH.
DR InterPro; IPR011304; L-lactate_DH.
DR InterPro; IPR018177; L-lactate_DH_AS.
DR InterPro; IPR022383; Lactate/malate_DH_C.
DR InterPro; IPR001236; Lactate/malate_DH_N.
DR InterPro; IPR015955; Lactate_DH/Glyco_Ohase_4_C.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR Pfam; PF02866; Ldh_1_C; 1.
DR Pfam; PF00056; Ldh_1_N; 1.
DR PIRSF; PIRSF000102; Lac_mal_DH; 1.
DR PRINTS; PR00086; LLDHDRGNASE.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF56327; SSF56327; 1.
DR TIGRFAMs; TIGR01771; L-LDH-NAD; 1.
DR PROSITE; PS00064; L_LDH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Cytoplasm; Isopeptide bond; NAD; Oxidoreductase;
KW Phosphoprotein; Reference proteome; Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P00338"
FT CHAIN 2..332
FT /note="L-lactate dehydrogenase A chain"
FT /id="PRO_0000168418"
FT ACT_SITE 193
FT /note="Proton acceptor"
FT /evidence="ECO:0000269|PubMed:19715328"
FT BINDING 29..57
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT BINDING 99
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT BINDING 106
FT /ligand="substrate"
FT BINDING 138
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT BINDING 138
FT /ligand="substrate"
FT BINDING 169
FT /ligand="substrate"
FT BINDING 248
FT /ligand="substrate"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P00338"
FT MOD_RES 5
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00338"
FT MOD_RES 5
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P06151"
FT MOD_RES 14
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00338"
FT MOD_RES 57
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00338"
FT MOD_RES 81
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00338"
FT MOD_RES 118
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00338"
FT MOD_RES 118
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P06151"
FT MOD_RES 126
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P00338"
FT MOD_RES 224
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P06151"
FT MOD_RES 232
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P06151"
FT MOD_RES 239
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:P06151"
FT MOD_RES 243
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P06151"
FT MOD_RES 309
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04642"
FT MOD_RES 310
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P00338"
FT MOD_RES 318
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P00338"
FT MOD_RES 318
FT /note="N6-succinyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P06151"
FT MOD_RES 322
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04642"
FT CROSSLNK 57
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P00338"
FT HELIX 4..8
FT /evidence="ECO:0007829|PDB:5NQB"
FT STRAND 9..11
FT /evidence="ECO:0007829|PDB:5NQB"
FT STRAND 20..26
FT /evidence="ECO:0007829|PDB:5NQB"
FT HELIX 30..41
FT /evidence="ECO:0007829|PDB:5NQB"
FT STRAND 46..51
FT /evidence="ECO:0007829|PDB:5NQB"
FT HELIX 55..66
FT /evidence="ECO:0007829|PDB:5NQB"
FT HELIX 67..71
FT /evidence="ECO:0007829|PDB:5NQB"
FT STRAND 76..79
FT /evidence="ECO:0007829|PDB:5NQB"
FT HELIX 83..86
FT /evidence="ECO:0007829|PDB:5NQB"
FT STRAND 90..94
FT /evidence="ECO:0007829|PDB:5NQB"
FT HELIX 106..127
FT /evidence="ECO:0007829|PDB:5NQB"
FT STRAND 132..135
FT /evidence="ECO:0007829|PDB:5NQB"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:5NQB"
FT HELIX 140..151
FT /evidence="ECO:0007829|PDB:5NQB"
FT HELIX 155..157
FT /evidence="ECO:0007829|PDB:5NQB"
FT STRAND 158..160
FT /evidence="ECO:0007829|PDB:5NQB"
FT HELIX 164..178
FT /evidence="ECO:0007829|PDB:5NQB"
FT HELIX 182..184
FT /evidence="ECO:0007829|PDB:5NQB"
FT STRAND 189..194
FT /evidence="ECO:0007829|PDB:5NQB"
FT HELIX 201..203
FT /evidence="ECO:0007829|PDB:5NQB"
FT HELIX 211..214
FT /evidence="ECO:0007829|PDB:5NQB"
FT TURN 216..219
FT /evidence="ECO:0007829|PDB:5NQB"
FT STRAND 220..222
FT /evidence="ECO:0007829|PDB:6P6U"
FT HELIX 228..245
FT /evidence="ECO:0007829|PDB:5NQB"
FT HELIX 250..264
FT /evidence="ECO:0007829|PDB:5NQB"
FT STRAND 269..276
FT /evidence="ECO:0007829|PDB:5NQB"
FT STRAND 288..296
FT /evidence="ECO:0007829|PDB:5NQB"
FT STRAND 299..304
FT /evidence="ECO:0007829|PDB:5NQB"
FT HELIX 310..327
FT /evidence="ECO:0007829|PDB:5NQB"
SQ SEQUENCE 332 AA; 36565 MW; 84E86C2E7D018EF7 CRC64;
MAALKDQLIH NLLKEEHVPQ NKITVVGVGA VGMACAISIL MKDLADELAL VDVMEDKLKG
EMMDLQHGSL FLRTPKIVSG KDYSVTANSK LVIITAGARQ QEGESRLNLV QRNVNIFKFI
IPNVVKYSPH CKLLVVSNPV DILTYVAWKI SGFPKNRVIG SGCNLDSARF RYLMGERLGV
HALSCHGWIL GEHGDSSVPV WSGMNVAGVS LKTLHPELGT DADKEQWKQV HKQVVDSAYE
VIKLKGYTTW AIGLSVADLA ESIMKNLRRV HPISTMLKGL YGIKEDVFLS VPCVLGQNGI
SDVVKVTLTS EEEAHLKKSA DTLWGIQKEL QF
