LDHA_PIG
ID LDHA_PIG Reviewed; 332 AA.
AC P00339;
DT 21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 159.
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 Sus scrofa (Pig).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Suina; Suidae; Sus.
OX NCBI_TaxID=9823;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Muscle;
RX PubMed=7937776; DOI=10.1073/pnas.91.20.9392;
RA Tsuji S., Qureshi M.A., Hou E.W., Fitch W.M., Li S.S.-L.;
RT "Evolutionary relationships of lactate dehydrogenases (LDHs) from mammals,
RT birds, an amphibian, fish, barley, and bacteria: LDH cDNA sequences from
RT Xenopus, pig, and rat.";
RL Proc. Natl. Acad. Sci. U.S.A. 91:9392-9396(1994).
RN [2]
RP PROTEIN SEQUENCE OF 2-332, AND ACETYLATION AT ALA-2.
RX PubMed=838465; DOI=10.1515/bchm2.1977.358.1.123;
RA Kiltz H.-H., Keil W., Griesbach M., Petry K., Meyer H.;
RT "The primary structure of porcine lactate dehydrogenase: isoenzymes M4 and
RT H4.";
RL Hoppe-Seyler's Z. Physiol. Chem. 358:123-127(1977).
RN [3]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH NAD AND SUBSTRATE
RP ANALOG.
RX PubMed=1678537; DOI=10.1098/rstb.1991.0047;
RA Dunn C.R., Wilks H.M., Halsall D.J., Atkinson T., Clarke A.R., Muirhead H.,
RA Holbrook J.J.;
RT "Design and synthesis of new enzymes based on the lactate dehydrogenase
RT framework.";
RL Philos. Trans. R. Soc. Lond., B, Biol. Sci. 332:177-184(1991).
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:1678537). Interacts with PTEN upstream
CC reading frame protein MP31 (By similarity).
CC {ECO:0000250|UniProtKB:P00338, ECO:0000269|PubMed:1678537}.
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; U07178; AAA50436.1; -; mRNA.
DR PIR; A00348; DEPGLM.
DR PDB; 9LDB; X-ray; 2.20 A; A/B=2-332.
DR PDB; 9LDT; X-ray; 2.00 A; A/B=2-332.
DR PDBsum; 9LDB; -.
DR PDBsum; 9LDT; -.
DR AlphaFoldDB; P00339; -.
DR SMR; P00339; -.
DR CORUM; P00339; -.
DR STRING; 9823.ENSSSCP00000014202; -.
DR iPTMnet; P00339; -.
DR PaxDb; P00339; -.
DR PeptideAtlas; P00339; -.
DR PRIDE; P00339; -.
DR Ensembl; ENSSSCT00005026037; ENSSSCP00005015775; ENSSSCG00005016454.
DR Ensembl; ENSSSCT00070013974; ENSSSCP00070011516; ENSSSCG00070007248.
DR eggNOG; KOG1495; Eukaryota.
DR HOGENOM; CLU_045401_0_2_1; -.
DR InParanoid; P00339; -.
DR OMA; ASCAEYI; -.
DR TreeFam; TF314963; -.
DR BRENDA; 1.1.1.27; 6170.
DR Reactome; R-SSC-70268; Pyruvate metabolism.
DR UniPathway; UPA00554; UER00611.
DR EvolutionaryTrace; P00339; -.
DR Proteomes; UP000008227; Unplaced.
DR Proteomes; UP000314985; Chromosome 2.
DR Genevisible; P00339; SS.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004459; F:L-lactate dehydrogenase activity; IBA:GO_Central.
DR GO; GO:0019752; P:carboxylic acid metabolic process; IEA:InterPro.
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; Direct protein sequencing;
KW Isopeptide bond; NAD; Oxidoreductase; Phosphoprotein; Reference proteome;
KW Ubl conjugation.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:838465"
FT CHAIN 2..332
FT /note="L-lactate dehydrogenase A chain"
FT /id="PRO_0000168416"
FT ACT_SITE 193
FT /note="Proton acceptor"
FT BINDING 29..57
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:1678537"
FT BINDING 99
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:1678537"
FT BINDING 106
FT /ligand="substrate"
FT BINDING 138
FT /ligand="NAD(+)"
FT /ligand_id="ChEBI:CHEBI:57540"
FT /evidence="ECO:0000269|PubMed:1678537"
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:0000269|PubMed:838465"
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 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 CONFLICT 233
FT /note="Q -> E (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 286
FT /note="D -> N (in Ref. 2; AA sequence)"
FT /evidence="ECO:0000305"
FT HELIX 4..8
FT /evidence="ECO:0007829|PDB:9LDT"
FT STRAND 20..26
FT /evidence="ECO:0007829|PDB:9LDT"
FT HELIX 30..41
FT /evidence="ECO:0007829|PDB:9LDT"
FT STRAND 46..51
FT /evidence="ECO:0007829|PDB:9LDT"
FT HELIX 55..67
FT /evidence="ECO:0007829|PDB:9LDT"
FT HELIX 68..71
FT /evidence="ECO:0007829|PDB:9LDT"
FT STRAND 76..82
FT /evidence="ECO:0007829|PDB:9LDT"
FT HELIX 83..86
FT /evidence="ECO:0007829|PDB:9LDT"
FT STRAND 90..94
FT /evidence="ECO:0007829|PDB:9LDT"
FT HELIX 106..109
FT /evidence="ECO:0007829|PDB:9LDT"
FT HELIX 110..127
FT /evidence="ECO:0007829|PDB:9LDT"
FT STRAND 132..135
FT /evidence="ECO:0007829|PDB:9LDT"
FT STRAND 137..139
FT /evidence="ECO:0007829|PDB:9LDT"
FT HELIX 140..151
FT /evidence="ECO:0007829|PDB:9LDT"
FT STRAND 157..160
FT /evidence="ECO:0007829|PDB:9LDT"
FT HELIX 164..178
FT /evidence="ECO:0007829|PDB:9LDT"
FT HELIX 182..184
FT /evidence="ECO:0007829|PDB:9LDT"
FT STRAND 189..191
FT /evidence="ECO:0007829|PDB:9LDT"
FT HELIX 201..203
FT /evidence="ECO:0007829|PDB:9LDT"
FT HELIX 211..214
FT /evidence="ECO:0007829|PDB:9LDT"
FT STRAND 219..222
FT /evidence="ECO:0007829|PDB:9LDT"
FT HELIX 228..245
FT /evidence="ECO:0007829|PDB:9LDT"
FT HELIX 250..264
FT /evidence="ECO:0007829|PDB:9LDT"
FT STRAND 269..276
FT /evidence="ECO:0007829|PDB:9LDT"
FT TURN 278..280
FT /evidence="ECO:0007829|PDB:9LDT"
FT STRAND 288..296
FT /evidence="ECO:0007829|PDB:9LDT"
FT STRAND 299..303
FT /evidence="ECO:0007829|PDB:9LDT"
FT HELIX 310..330
FT /evidence="ECO:0007829|PDB:9LDT"
SQ SEQUENCE 332 AA; 36619 MW; FD3B4673557C9B72 CRC64;
MATLKDQLIH NLLKEEHVPH NKITVVGVGA VGMACAISIL MKELADEIAL VDVMEDKLKG
EMMDLQHGSL FLRTPKIVSG KDYNVTANSR LVVITAGARQ QEGESRLNLV QRNVNIFKFI
IPNIVKYSPN CKLLVVSNPV DILTYVAWKI SGFPKNRVIG SGCNLDSARF RYLMGERLGV
HPLSCHGWIL GEHGDSSVPV WSGVNVAGVS LKNLHPELGT DADKEHWKAV HKQVVDSAYE
VIKLKGYTSW AIGLSVADLA ESIMKNLRRV HPISTMIKGL YGIKEDVFLS VPCILGQNGI
SDVVKVTLTP EEEAHLKKSA DTLWGIQKEL QF
