Reviewed, UniProtKB/Swiss-Prot P00338 (LDHA_HUMAN)

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
    Renal carcinoma antigen NY-REN-59
    Cell proliferation-inducing gene 19 protein

Gene names

Name:	LDHA
ORF Names:	PIG19

Organism

Homo sapiens (Human) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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. Ref.15
Subcellular location	Cytoplasm.
Involvement in disease	Defects in LDHA are a cause of exertional myoglobinuria.
Sequence similarities	Belongs to the LDH/MDH superfamily. LDH family.

Ontologies

Keywords
Biological process	Glycolysis
Cellular component	Cytoplasm
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation
Ligand	NAD
Molecular function	Oxidoreductase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing
Gene Ontology (GO)
Biological process	anaerobic glycolysis Inferred from electronic annotation. Source: InterPro oxidation reduction Inferred from electronic annotation. Source: UniProtKB-KW pyruvate metabolic process Inferred from Experiment. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: ProtInc
Molecular function	L-lactate dehydrogenase activity Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
NDRG1	Q92597	1	EBI-681495,EBI-716486
XRN1	Q8IZH2	1	EBI-372327,EBI-372406

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P00338-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P00338-2)

The sequence of this isoform differs from the canonical sequence as follows:
     230-274: VHKQVVESAY...KNLRRVHPVS → CRYTLGDPKG...ACCPFYLICD

Note: No experimental confirmation available.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.8

Chain

2 – 332

331

L-lactate dehydrogenase A chain

PRO_0000168411

Regions

Nucleotide binding

29 – 57

29

NAD

Sites

Active site

193

1

Proton acceptor

Binding site

99

1

NAD

Binding site

106

1

Substrate

Binding site

138

1

NAD or substrate

Binding site

169

1

Substrate

Binding site

248

1

Substrate

Amino acid modifications

Modified residue

2

1

N-acetylalanine Ref.8

Modified residue

5

1

N6-acetyllysine Ref.14

Modified residue

14

1

N6-acetyllysine Ref.14

Modified residue

57

1

N6-acetyllysine Ref.14

Modified residue

81

1

N6-acetyllysine Ref.14

Modified residue

118

1

N6-acetyllysine Ref.14

Modified residue

126

1

N6-acetyllysine Ref.14

Modified residue

222

1

N6-acetyllysine Ref.14

Modified residue

239

1

Phosphotyrosine Ref.11 Ref.12

Modified residue

278

1

N6-acetyllysine Ref.14

Modified residue

318

1

N6-acetyllysine Ref.14

Natural variations

Alternative sequence

230 – 274

45

VHKQV…VHPVS → CRYTLGDPKGAAILKSSDVI SFHCLGYNRILGGGCACCPF YLICD in isoform 2.

VSP_014261

Natural variant

161

1

S → R: dbSNP rs5030621.

VAR_059374

Natural variant

222

1

K → E

VAR_004180

Natural variant

315

1

R → C in LDHA deficiency. Ref.16

VAR_004181

Secondary structure

1

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332

Helix Strand Turn

Details...

Helix

4 – 8

5

Beta strand

9 – 13

5

Beta strand

20 – 26

7

Helix

30 – 41

12

Beta strand

46 – 51

6

Helix

55 – 66

12

Helix

67 – 71

5

Beta strand

76 – 79

4

Helix

83 – 86

4

Beta strand

90 – 94

5

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

Beta strand

220 – 222

3

Helix

228 – 245

18

Helix

250 – 264

15

Beta strand

269 – 276

8

Beta strand

288 – 296

9

Beta strand

299 – 304

6

Helix

310 – 327

18

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: 401E8604CEB7F908	FASTA	332	36,689
	10 20 30 40 50 60 MATLKDQLIY NLLKEEQTPQ NKITVVGVGA VGMACAISIL MKDLADELAL VDVIEDKLKG 70 80 90 100 110 120 EMMDLQHGSL FLRTPKIVSG KDYNVTANSK LVIITAGARQ QEGESRLNLV QRNVNIFKFI 130 140 150 160 170 180 IPNVVKYSPN CKLLIVSNPV DILTYVAWKI SGFPKNRVIG SGCNLDSARF RYLMGERLGV 190 200 210 220 230 240 HPLSCHGWVL GEHGDSSVPV WSGMNVAGVS LKTLHPDLGT DKDKEQWKEV HKQVVESAYE 250 260 270 280 290 300 VIKLKGYTSW AIGLSVADLA ESIMKNLRRV HPVSTMIKGL YGIKDDVFLS VPCILGQNGI 310 320 330 SDLVKVTLTS EEEARLKKSA DTLWGIQKEL QF
	Isoform 2. Checksum: 24B2D9490996BD0D	FASTA	332	36,481
	10 20 30 40 50 60 MATLKDQLIY NLLKEEQTPQ NKITVVGVGA VGMACAISIL MKDLADELAL VDVIEDKLKG 70 80 90 100 110 120 EMMDLQHGSL FLRTPKIVSG KDYNVTANSK LVIITAGARQ QEGESRLNLV QRNVNIFKFI 130 140 150 160 170 180 IPNVVKYSPN CKLLIVSNPV DILTYVAWKI SGFPKNRVIG SGCNLDSARF RYLMGERLGV 190 200 210 220 230 240 HPLSCHGWVL GEHGDSSVPV WSGMNVAGVS LKTLHPDLGT DKDKEQWKEC RYTLGDPKGA 250 260 270 280 290 300 AILKSSDVIS FHCLGYNRIL GGGCACCPFY LICDTMIKGL YGIKDDVFLS VPCILGQNGI 310 320 330 SDLVKVTLTS EEEARLKKSA DTLWGIQKEL QF

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Nucleotide sequences of the cDNA and an intronless pseudogene for human lactate dehydrogenase-A isozyme." Tsujibo H., Tiano H.F., Li S.S.-L. Eur. J. Biochem. 147:9-15(1985) [PubMed: 3838278] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Genomic organization of human lactate dehydrogenase-A gene." Chung F.Z., Tsujibo H., Bhattacharyya U., Sharief F.S., Li S.S.-L. Biochem. J. 231:537-541(1985) [PubMed: 3000353] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	"Identification of a human proliferation-inducing gene." Kim J.W. Submitted (SEP-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[4]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[5]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., LaBaer J. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
[6]	Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S. Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT GLU-222. Tissue: Gastric carcinoma.
[7]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Bone marrow.
[8]	Bienvenut W.V. Submitted (MAR-2005) to UniProtKB Cited for: PROTEIN SEQUENCE OF 2-14; 43-57; 60-73; 77-112; 133-149; 158-169; 233-243; 306-315 AND 319-328, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT ALA-2, MASS SPECTROMETRY. Tissue: B-cell lymphoma.
[9]	"Genotypic analysis of families with lactate dehydrogenase A (M) deficiency by selective DNA amplification." Maekawa M., Sudo K., Li S.S., Kanno T. Hum. Genet. 88:34-38(1991) [PubMed: 1959923] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 250-254.
[10]	"Antigens recognized by autologous antibody in patients with renal-cell carcinoma." Scanlan M.J., Gordan J.D., Williamson B., Stockert E., Bander N.H., Jongeneel C.V., Gure A.O., Jaeger D., Jaeger E., Knuth A., Chen Y.-T., Old L.J. Int. J. Cancer 83:456-464(1999) [PubMed: 10508479] [Abstract] Cited for: IDENTIFICATION AS A RENAL CANCER ANTIGEN. Tissue: Renal cell carcinoma.
[11]	"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells." Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J. Nat. Biotechnol. 23:94-101(2005) [PubMed: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-239, MASS SPECTROMETRY.
[12]	"Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-239, MASS SPECTROMETRY.
[13]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[14]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-5; LYS-14; LYS-57; LYS-81; LYS-118; LYS-126; LYS-222; LYS-278 AND LYS-318, MASS SPECTROMETRY.
[15]	"Structural basis for altered activity of M- and H-isozyme forms of human lactate dehydrogenase." Read J.A., Winter V.J., Eszes C.M., Sessions R.B., Brady R.L. Proteins 43:175-185(2001) [PubMed: 11276087] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) IN COMPLEX WITH NADH AND SUBSTRATE ANALOG, HOMOTETRAMERIZATION.
[16]	"Molecular analysis of genetic mutation in electrophoretic variant of human lactate dehydrogenase-A(M) subunit." Sudo K., Maekawa M., Shioya M., Ikeda K., Takahashi N., Isogai Y., Li S.S.-L., Kanno T., Machida K., Toriumi J. Biochem. Int. 27:1051-1057(1992) [PubMed: 1445373] [Abstract] Cited for: VARIANT CYS-315.
[17]	"Fast-type electrophoretic variant of lactate dehydrogenase M(A) and comparison with other missense mutations in lactate dehydrogenase M(A) and H(B) genes." Maekawa M., Sudo K., Kobayashi A., Sugiyama E., Li S.S.-L., Kanno T. Clin. Chem. 40:665-668(1994) [PubMed: 7908613] [Abstract] Cited for: VARIANT GLU-222.
+	Additional computationally mapped references.

Web resources

GeneReviews

Wikipedia

Lactate dehydrogenase entry

Protein Spotlight

Another dark horse - Issue 109 of September 2009

Cross-references

Sequence databases

EMBLGenBankDDBJ

X02152 mRNA. Translation: CAA26088.1.
X03077 , X03078, X03079, X03080, X03081, X03082, X03083 Genomic DNA. Translation: CAA26879.1.
AY423727 mRNA. Translation: AAS00490.1.
AK130587 mRNA. Translation: BAC85389.1.
CR456775 mRNA. Translation: CAG33056.1.
CR541714 mRNA. Translation: CAG46515.1.
AK223078 mRNA. Translation: BAD96798.1.
BC067223 mRNA. Translation: AAH67223.1.
S66853 Genomic DNA. Translation: AAB20418.1.

IPI

IPI00217966.
IPI00607708.

PIR

DEHULM. A00347.

RefSeq

NP_001158887.1.
NP_005557.1.

UniGene

Hs.2795

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1I10	X-ray	2.30	A/B/C/D/E/F/G/H	2-332	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

P00338. 5 interactions.

STRING

P00338.

PTM databases

PhosphoSite

P00338.

2-D gel databases

Aarhus/Ghent-2DPAGE

2207. NEPHGE.

Cornea-2DPAGE

P00338.

DOSAC-COBS-2DPAGE

P00338.

OGP

P00338.

REPRODUCTION-2DPAGE

IPI00217966.

Proteomic databases

PeptideAtlas

P00338.

PRIDE

P00338.

Genome annotation databases

Ensembl

ENST00000227157; ENSP00000227157; ENSG00000134333; Homo sapiens. [Genome view]
ENST00000379412; ENSP00000368722; ENSG00000134333; Homo sapiens. [Genome view]
ENST00000396222; ENSP00000379524; ENSG00000134333; Homo sapiens. [Genome view]
ENST00000422447; ENSP00000395337; ENSG00000134333; Homo sapiens. [Genome view]
ENST00000430553; ENSP00000406172; ENSG00000134333; Homo sapiens. [Genome view]
ENST00000445376; ENSP00000404535; ENSG00000134333; Homo sapiens. [Genome view]

GeneID

3939.

NMPDR

fig|9606.3.peg.5346.

UCSC

uc001mok.2. human.

Organism-specific databases

CTD

3939.

GeneCards

GC11P018372.

H-InvDB

HIX0009487.

HGNC

HGNC:6535. LDHA.

HPA

CAB015336.

MIM

150000. gene+phenotype.

Orphanet

2364. Lactate dehydrogenase deficiency.

PharmGKB

PA30319.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

P00338.

HOVERGEN

P00338.

OMA

KEEHVPQ.

Enzyme and pathway databases

BRENDA

1.1.1.27. 247.

Pathway_Interaction_DB

hif1_tfpathway. HIF-1-alpha transcription factor network.

Reactome

REACT_1046. Pyruvate metabolism and TCA cycle.
REACT_474. Metabolism of carbohydrates.

Gene expression databases

ArrayExpress

P00338.

Bgee

P00338.

CleanEx

HS_LDHA.

Genevestigator

P00338.

GermOnline

ENSG00000134333. Homo sapiens.

Family and domain databases

InterPro

IPR001557. L-lactate/malate_DH.
IPR011304. L-lactate_DH.
IPR018177. L-lactate_DH_AS.
IPR001236. Lactate/malate_DH.
IPR015955. Lactate_DH/Glyco_Ohase_4_C.
[Graphical view]

Gene3D

G3DSA:3.90.110.10. lact_mal_DH. 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.

TIGRFAMs

TIGR01771. L-LDH-NAD. 1 hit.

PROSITE

PS00064. L_LDH. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00157. NADH.

NextBio

15469.

SOURCE

Search...

Entry information

Entry name

LDHA_HUMAN

Accession

Primary (citable) accession number: P00338
Secondary accession number(s): Q53G53, Q6IBM7, Q6ZNV1

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 23, 2007
Last modified:	November 3, 2009
This is version 126 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.