P04642 (LDHA_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
L-lactate dehydrogenase A chain
Short name=LDH-A
EC=1.1.1.27

Alternative name(s):
LDH muscle subunit
Short name=LDH-M

Gene names

Name:	Ldha
Synonyms:	Ldh-1, Ldh1

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	332 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Catalytic activity	(S)-lactate + NAD+ = pyruvate + NADH.
Pathway	Fermentation; pyruvate fermentation to lactate; (S)-lactate from pyruvate: step 1/1.
Subunit structure	Homotetramer.
Subcellular location	Cytoplasm.
Post-translational modification	ISGylated By similarity.
Sequence similarities	Belongs to the LDH/MDH superfamily. LDH family.

Ontologies

Keywords
Biological process	Glycolysis
Cellular component	Cytoplasm
Ligand	NAD
Molecular function	Oxidoreductase
PTM	Acetylation Phosphoprotein Ubl conjugation
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	NAD metabolic process Inferred from direct assay PubMed 17447164. Source: RGD cellular carbohydrate metabolic process Inferred from electronic annotation. Source: InterPro glycolysis Inferred from electronic annotation. Source: UniProtKB-KW lactate metabolic process Inferred from direct assay PubMed 17447164. Source: RGD positive regulation of apoptotic process Inferred from direct assay PubMed 9465046. Source: RGD post-embryonic organ development Inferred from expression pattern PubMed 6849973. Source: RGD response to cAMP Inferred from expression pattern PubMed 6300127. Source: RGD response to drug Inferred from expression pattern PubMed 11176097. Source: RGD response to estrogen stimulus Inferred from expression pattern PubMed 17010207. Source: RGD response to glucose stimulus Inferred from expression pattern PubMed 11457846. Source: RGD response to hydrogen peroxide Inferred from expression pattern PubMed 16154111. Source: RGD response to hypoxia Inferred from expression pattern PubMed 12678657. Source: RGD response to nutrient Inferred from expression pattern PubMed 15110778. Source: RGD
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	L-lactate dehydrogenase activity Inferred from direct assay PubMed 17447164. Source: RGD NAD binding Inferred from direct assay PubMed 17447164. Source: RGD identical protein binding Inferred from direct assay PubMed 7138505. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.3

Chain

2 – 332

331

L-lactate dehydrogenase A chain

PRO_0000168419

Regions

Nucleotide binding

29 – 57

29

NAD By similarity

Sites

Active site

193

1

Proton acceptor By similarity

Binding site

99

1

NAD By similarity

Binding site

106

1

Substrate By similarity

Binding site

138

1

NAD or substrate By similarity

Binding site

169

1

Substrate By similarity

Binding site

248

1

Substrate By similarity

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.3

Modified residue

5

1

N6-acetyllysine By similarity

Modified residue

14

1

N6-acetyllysine By similarity

Modified residue

57

1

N6-acetyllysine By similarity

Modified residue

81

1

N6-acetyllysine By similarity

Modified residue

118

1

N6-acetyllysine By similarity

Modified residue

126

1

N6-acetyllysine By similarity

Modified residue

239

1

Phosphotyrosine By similarity

Modified residue

318

1

N6-acetyllysine By similarity

Experimental info

Sequence conflict

184 – 191

8

SCHGWVLG → ADLGEVV AA sequence Ref.4

Sequence conflict

324

1

W → G in AAA41508. Ref.5

Sequence conflict

326

1

I → T in AAA41508. Ref.5

Secondary structure

1

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332

Helix Strand Turn

Details...

Helix

4 – 8

5

Beta strand

9 – 11

3

Beta strand

20 – 26

7

Helix

30 – 41

12

Beta strand

46 – 51

6

Helix

55 – 67

13

Helix

68 – 71

4

Beta strand

76 – 79

4

Helix

83 – 86

4

Beta strand

89 – 94

6

Helix

106 – 109

4

Helix

110 – 127

18

Beta strand

132 – 135

4

Beta strand

137 – 139

3

Helix

140 – 151

12

Helix

155 – 157

3

Beta strand

158 – 160

3

Helix

164 – 178

15

Helix

182 – 184

3

Beta strand

189 – 191

3

Helix

201 – 203

3

Helix

211 – 214

4

Turn

216 – 219

4

Helix

228 – 245

18

Helix

250 – 264

15

Beta strand

269 – 276

8

Helix

280 – 282

3

Beta strand

288 – 296

9

Beta strand

299 – 304

6

Helix

310 – 327

18

Sequences

	Sequence		Length	Mass (Da)
	P04642 [UniParc]. Last modified August 13, 1987. Version 1. Checksum: 5E432659D032A4D3	FASTA	332	36,451
	10 20 30 40 50 60 MAALKDQLIV NLLKEEQVPQ NKITVVGVGA VGMACAISIL MKDLADELAL VDVIEDKLKG 70 80 90 100 110 120 EMMDLQHGSL FLKTPKIVSS KDYSVTANSK LVIITAGARQ QEGESRLNLV QRNVNIFKFI 130 140 150 160 170 180 IPNVVKYSPQ CKLLIVSNPV DILTYVAWKI SGFPKNRVIG SGCNLDSARF RYLMGERLGV 190 200 210 220 230 240 HPLSCHGWVL GEHGDSSVPV WSGVNVAGVS LKSLNPQLGT DADKEQWKDV HKQVVDSAYE 250 260 270 280 290 300 VIKLKGYTSW AIGLSVADLA ESIMKNLRRV HPISTMIKGL YGIKEDVFLS VPCILGQNGI 310 320 330 SDVVKVTLTP DEEARLKKSA DTLWGIQKEL QF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Epidermal growth factor or serum stimulation of rat fibroblasts induces an elevation in mRNA levels for lactate dehydrogenase and other glycolytic enzymes." Matrisian L.M., Rautmann G., Magun B.E., Breathnach R. Nucleic Acids Res. 13:711-726(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Lung.
[3]	Bienvenut W.V., von Kriegsheim A.F., Kolch W. Submitted (JUN-2009) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-14; 43-57; 91-99; 107-112; 119-126; 233-243; 306-315 AND 319-328, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: Fibroblast and Pheochromocytoma.
[4]	"Identification of a nucleic acid helix-destabilizing protein from rat liver as lactate dehydrogenase-5." Williams K.R., Reddigari S., Patel G.L. Proc. Natl. Acad. Sci. U.S.A. 82:5260-5264(1985) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 82-99; 127-132; 156-157; 170-190; 234-245; 306-315 AND 319-328.
[5]	"Characterization of the folding structure of 3'-end of lactate dehydrogenase A-mRNA isolated from hormone stimulated rat C-6 glioma cell culture." Bae S.C., Lee S.K. J. Microbiol. 25:94-102(1987) Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 274-332. Tissue: Liver.
[6]	Lubec G., Chen W.-Q. Submitted (SEP-2006) to UniProtKB Cited for: PROTEIN SEQUENCE OF 319-328, MASS SPECTROMETRY.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X01964 mRNA. Translation: CAA26000.1.
BC084698 mRNA. Translation: AAH84698.1.
M54926 mRNA. Translation: AAA41508.1.

IPI

IPI00197711.

PIR

A23083.

RefSeq

NP_058721.1. NM_017025.1.

UniGene

Rn.107896.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
4AJ1	X-ray	1.87	A/B/C/D	2-332	[»]
4AJ2	X-ray	1.75	A/B/C/D	2-332	[»]
4AJ4	X-ray	1.90	A/B/C/D	1-332	[»]
4AJE	X-ray	2.35	A/B/C/D	2-332	[»]
4AJH	X-ray	1.93	A/B/C/D	2-332	[»]
4AJI	X-ray	1.93	A/B/C/D	2-332	[»]
4AJJ	X-ray	1.75	A/B/C/D	2-332	[»]
4AJK	X-ray	2.03	A/B/C/D	2-332	[»]
4AJL	X-ray	1.77	A/B/C/D	2-332	[»]
4AJN	X-ray	2.10	A/B/C/D	2-332	[»]
4AJO	X-ray	1.96	A/B/C/D	2-332	[»]
4AL4	X-ray	1.78	A/B/C/D	2-332	[»]

ProteinModelPortal

P04642.

SMR

P04642. Positions 2-332.

ModBase

Search...

Protein-protein interaction databases

IntAct

P04642. 3 interactions.

MINT

MINT-4568905.

PTM databases

PhosphoSite

P04642.

Proteomic databases

PaxDb

P04642.

PRIDE

P04642.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSRNOT00000017468; ENSRNOP00000017468; ENSRNOG00000013009.

GeneID

24533.

KEGG

rno:24533.

Organism-specific databases

CTD

3939.

RGD

2996. Ldha.

Phylogenomic databases

eggNOG

COG0039.

GeneTree

ENSGT00550000074541.

HOGENOM

HOG000213793.

HOVERGEN

HBG000462.

InParanoid

P04642.

KO

K00016.

OMA

AIACDQK.

OrthoDB

EOG4RR6HR.

Enzyme and pathway databases

BioCyc

MetaCyc:MONOMER-11604.

UniPathway

UPA00554; UER00611.

Gene expression databases

ArrayExpress

P04642.

Genevestigator

P04642.

GermOnline

ENSRNOG00000013009. Rattus norvegicus.

Family and domain databases

Gene3D

3.40.50.720. 1 hit.
3.90.110.10. 1 hit.

InterPro

IPR001557. L-lactate/malate_DH.
IPR011304. L-lactate_DH.
IPR018177. L-lactate_DH_AS.
IPR022383. Lactate/malate_DH_C.
IPR001236. Lactate/malate_DH_N.
IPR015955. Lactate_DH/Glyco_Ohase_4_C.
IPR016040. NAD(P)-bd_dom.
[Graphical view]

PANTHER

PTHR11540. PTHR11540. 1 hit.

Pfam

PF02866. Ldh_1_C. 1 hit.
PF00056. Ldh_1_N. 1 hit.
[Graphical view]

PIRSF

PIRSF000102. Lac_mal_DH. 1 hit.

PRINTS

PR00086. LLDHDRGNASE.

SUPFAM

SSF56327. Lactate_DH/Glyco_hydro_4_C. 1 hit.

TIGRFAMs

TIGR01771. L-LDH-NAD. 1 hit.

PROSITE

PS00064. L_LDH. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P04642.

NextBio

603598.

Entry information

Entry name

LDHA_RAT

Accession

Primary (citable) accession number: P04642

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 13, 1987
Last sequence update:	August 13, 1987
Last modified:	April 3, 2013
This is version 123 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program