LDHA lactate dehydrogenase A [Homo sapiens] - Gene

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Summary

Official Symbol: LDHAprovided by HGNC
Official Full Name: lactate dehydrogenase Aprovided by HGNC
Primary source: HGNC:6535
Locus tag: PIG19
See related: Ensembl:ENSG00000134333; HPRD:01025; MIM:150000; Vega:OTTHUMG00000167721
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: LDH1; LDHM; GSD11; PIG19
Summary: The protein encoded by this gene catalyzes the conversion of L-lactate and NAD to pyruvate and NADH in the final step of anaerobic glycolysis. The protein is found predominantly in muscle tissue and belongs to the lactate dehydrogenase family. Mutations in this gene have been linked to exertional myoglobinuria. Multiple transcript variants encoding different isoforms have been found for this gene. The human genome contains several non-transcribed pseudogenes of this gene. [provided by RefSeq, Sep 2008]

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Genomic context

Location :: 11p15.4

Sequence :: Chromosome: 11; NC_000011.9 (18415936..18429765)

See LDHA in Epigenomics, MapViewer

Chromosome 11 - NC_000011.9 Genomic Context describing neighboring genes

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Genomic regions, transcripts, and products

Genomic Sequence

Go to nucleotideGraphics FASTA GenBank

Go to reference sequence details

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Bibliography

GeneRIFs: Gene References Into Functions What's a GeneRIF?

LDH-A reduction resulted in an inhibited cancer cell proliferation, elevated intracellular oxidative stress, and induction of mitochondrial pathway apoptosis.
Title: LDH-A silencing suppresses breast cancer tumorigenicity through induction of oxidative stress mediated mitochondrial pathway apoptosis.
A protein encoded by this locus was found to be differentially expressed in postmortem brains from patients with atypical frontotemporal lobar degeneration.
Title: Proteomic analysis identifies dysfunction in cellular transport, energy, and protein metabolism in different brain regions of atypical frontotemporal lobar degeneration.
Results show that S-100B, MIA and LDH levels were significantly higher in patients with advanced melanoma than in disease-free patients or healthy controls.
Title: Evaluation of multiple serum markers in advanced melanoma.
LDH-A is tyrosine phosphorylated and activated by FGFR1 in cancer cells.
Title: Tyrosine phosphorylation of lactate dehydrogenase A is important for NADH/NAD(+) redox homeostasis in cancer cells.
Case Report: describe an elderly patient with physical therapy-induced rhabdomyolysis complicated by acute kidney injury associated with reduced skeletal muscle LDH-A activity.
Title: Physical therapy-induced rhabdomyolysis and acute kidney injury associated with reduced activity of muscle lactate dehydrogenase A.
Serum LDH and tissue LDH5 levels are complementary features that help to characterize the activity of LDH in colorectal cancer and have a potent value in predicting response to chemotherapy.
Title: Prognostic and predictive role of lactate dehydrogenase 5 expression in colorectal cancer patients treated with PTK787/ZK 222584 (vatalanib) antiangiogenic therapy.
High LDH is associated with M1b prostate cancer.
Title: Lactate dehydrogenase, Gleason score and HER-2 overexpression are significant prognostic factors for M1b prostate cancer.
LDH5 is overexpressed in non-small cell lung cancer and could serve as a marker for malignancy. LDH5 correlates positively with the prognostic marker transketolase like 1 protein.
Title: Lactate-dehydrogenase 5 is overexpressed in non-small cell lung cancer and correlates with the expression of the transketolase-like protein 1.
High lactate dehydrogenase is associated with acute adult T-cell leukemia/lymphoma.
Title: Different prognostic factors for survival in acute and lymphomatous adult T-cell leukemia/lymphoma.
Presented are QM/MM calculations that show differences in geometries of active sites of M(4) and H(4) isoforms of human LDH ligated with oxamate, pyruvate or L-lactate.
Title: Differences and similarities in binding of pyruvate and L-lactate in the active site of M4 and H4 isoforms of human lactate dehydrogenase.

Submit: New GeneRIF Correction See all (30)

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Phenotypes

Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Exertional myoglobinuria due to deficiency of LDH-A

MIM: 150000

Genome-wide association study identifies two novel regions at 11p15.5-p13 and 1p31 with major impact on acute-phase serum amyloid A.

HIV-1 protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	HIV-1 gp120/41 (SFVenvBX08)-expressing microglia exhibit a 170% increase in lactate dehydrogenase (LDH) release	PubMed
Envelope transmembrane glycoprotein gp41	env	A lentivirus lytic peptide 1 (LLP-1) corresponding to the carboxyl terminus of HIV-1 gp41 induces a significant lactate dehydrogenase (LDH, a marker of cell death) release from human neuronal and glial cell lines	PubMed
Tat	tat	Upregulation of actin, heat shock protein 90 and mitochondrial single-stranded DNA binding protein, and downregulation of lactate dehydrogenase are identified in human astrocytes expressing Tat	PubMed

Go to the HIV-1, Human Protein Interaction Database

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Products	Interactant	Other Gene	Source	Pubs	Description
P00338	O60706	ABCC9	HPRD	PubMed
P00338	P63167	DYNLL1	HPRD	PubMed
P00338	Q14103	HNRNPD	HPRD	PubMed
P00338	Q14654	KCNJ11	HPRD	PubMed
P00338	P00338	LDHA	HPRD	PubMed
P00338	Q92597	NDRG1	HPRD	PubMed
P00338	Q8IZH2	XRN1	HPRD	PubMed
BioGRID:110131	BioGRID:115371	ABCC9	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110131	BioGRID:115331	HDAC5	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110131	BioGRID:108918	KAT2A	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110131	BioGRID:115779	KAT5	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110131	BioGRID:109969	KCNJ11	BioGRID	PubMed	Affinity Capture-Western
BioGRID:110131	BioGRID:204968	Mapk13	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110131	BioGRID:115669	NDRG1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110131	BioGRID:111136	PCK1	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110131	BioGRID:111142	PCNA	BioGRID	PubMed	Reconstituted Complex
BioGRID:110131	BioGRID:111657	PSMA3	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110131	BioGRID:112497	SUMO2	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110131	BioGRID:113164	UBC	BioGRID	PubMed	Affinity Capture-MS
BioGRID:110131	BioGRID:116168	YWHAQ	BioGRID	PubMed	Affinity Capture-MS

Function	Evidence Code	Pubs
L-lactate dehydrogenase activity	NAS Non-traceable Author Statement more info	PubMed
nucleotide binding	IEA Inferred from Electronic Annotation more info
oxidoreductase activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
cellular carbohydrate metabolic process	IEA Inferred from Electronic Annotation more info
glycolysis	NAS Non-traceable Author Statement more info	PubMed
pyruvate metabolic process	TAS Traceable Author Statement more info
small molecule metabolic process	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
cytoplasm	IEA Inferred from Electronic Annotation more info
cytosol	TAS Traceable Author Statement more info

General protein information

Preferred Names: L-lactate dehydrogenase A chain

Names: L-lactate dehydrogenase A chain; LDH-A; LDH-M; LDH muscle subunit; lactate dehydrogenase M; proliferation-inducing gene 19; renal carcinoma antigen NY-REN-59; cell proliferation-inducing gene 19 protein

NP_001128711.1

EC 1.1.1.27

NP_001158886.1

EC 1.1.1.27

NP_001158887.1

EC 1.1.1.27

NP_001158888.1

EC 1.1.1.27

NP_005557.1

EC 1.1.1.27

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NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_008185.1 RefSeqGene

Range

4955..18784

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001135239.1 → NP_001128711.1 L-lactate dehydrogenase A chain isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an in-frame exon in the central coding region, compared to variant 1. The resulting isoform (2) lacks a segment of the LDH domain but has the same N- and C-termini, compared to isoform 1.

Source sequence(s)

AC084117, AK296667, BM995301, DB502157

Consensus CDS

CCDS44549.1

UniProtKB/Swiss-Prot

P00338

Related

ENSP00000406172, OTTHUMP00000236636, ENST00000430553, OTTHUMT00000395878

Conserved Domains (2) summary

pfam02866
Location:106 – 265
Blast Score: 323

Ldh_1_C; lactate/malate dehydrogenase, alpha/beta C-terminal domain

cl09931
Location:37 – 81
Blast Score: 162

NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins
NM_001165414.1 → NP_001158886.1 L-lactate dehydrogenase A chain isoform 3

Status: REVIEWED

Description

Transcript Variant: This variant (3) uses an alternate 5' exon that results in a distinct 5' UTR and causes translation initiation at an alternate start codon, compared to variant 1. The resulting isoform (3) has a longer N-terminus, compared to isoform 1.

Source sequence(s)

AC084117, AK298834, AK307477, BM995301, DC392310, DC396757

Consensus CDS

CCDS53609.1

UniProtKB/Swiss-Prot

P00338

Related

ENSP00000445175, ENST00000540430

Conserved Domains (2) summary

cd05293
Location:48 – 358
Blast Score: 1480

LDH_1; A subgroup of L-lactate dehydrogenases

TIGR01771
Location:67 – 353
Blast Score: 1124

L-LDH-NAD; L-lactate dehydrogenase
NM_001165415.1 → NP_001158887.1 L-lactate dehydrogenase A chain isoform 4

Status: REVIEWED

Description

Transcript Variant: This variant (4) differs in the 3' UTR and has multiple differences in the 3' coding region, compared to variant 1, one of which results in a frameshift. The resulting isoform (4) lacks a segment of the LDH domain and has a shorter and distinct C-terminus, compared to isoform 1.

Source sequence(s)

AC084117, AK130587, AK307477, BM995301, DB502157

Consensus CDS

CCDS53610.1

UniProtKB/Swiss-Prot

P00338

Related

ENSP00000379524, OTTHUMP00000165206, ENST00000396222, OTTHUMT00000258173

Conserved Domains (1) summary

cl09931
Location:19 – 229
Blast Score: 1012

NADB_Rossmann; Rossmann-fold NAD(P)(+)-binding proteins
NM_001165416.1 → NP_001158888.1 L-lactate dehydrogenase A chain isoform 5

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks an alternate exon in the 3' coding region, compared to variant 1, which results in a frameshift. The resulting isoform (5) lacks a segment of the LDH domain and has a shorter and distinct C-terminus, compared to isoform 1.

Source sequence(s)

AC084117, BG760757, BM995301, DB502157

Consensus CDS

CCDS53611.1

UniProtKB/Swiss-Prot

P00338

Related

ENSP00000227157, OTTHUMP00000165207, ENST00000227157, OTTHUMT00000258174

Conserved Domains (1) summary

cd05293
Location:19 – 240
Blast Score: 1041

LDH_1; A subgroup of L-lactate dehydrogenases
NM_005566.3 → NP_005557.1 L-lactate dehydrogenase A chain isoform 1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the predominant isoform (1).

Source sequence(s)

AC084117, BC067223, BG424022, BM995301, DB502157

Consensus CDS

CCDS7839.1

UniProtKB/Swiss-Prot

P00338

Related

ENSP00000395337, OTTHUMP00000165205, ENST00000422447, OTTHUMT00000258172

Conserved Domains (2) summary

cd05293
Location:19 – 329
Blast Score: 1469

LDH_1; A subgroup of L-lactate dehydrogenases

TIGR01771
Location:38 – 324
Blast Score: 1120

L-LDH-NAD; L-lactate dehydrogenase

RNA

NR_028500.1 RNA Sequence

Description

Transcript Variant: This variant (6) lacks an alternate internal exon, compared to variant 1. This variant is represented as non-coding because the use of the 5'-most supported translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

AC084117, AK307477, BM995301, DB502157

RefSeqs of Annotated Genomes: Build 37.3

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh37.p5 Primary Assembly

Genomic

NC_000011.9 Reference GRCh37.p5 Primary Assembly

Range

18415936..18429765

Download

GenBank, FASTA, Sequence Viewer (Graphics)

Alternate HuRef

Genomic

AC_000143.1 Alternate HuRef

Range

18101143..18114981

Download

GenBank, FASTA, Sequence Viewer (Graphics)

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Related Sequences

Nucleotide		Protein
Heading	Accession and Version	Protein
genomic	AC084117.6 (102936..116374)	None
genomic	CH471064.2	EAW68395.1
		EAW68396.1
		EAW68397.1
genomic	X03077.1	CAA26879.1
mRNA	AK026515.1	None
mRNA	AK130035.1	None
mRNA	AK130105.1	None
mRNA	AK130587.1	BAC85389.1
mRNA	AK223078.1	BAD96798.1
mRNA	AK296089.1	BAG58843.1
mRNA	AK296667.1	BAG59264.1
mRNA	AK298834.1	BAH12879.1
mRNA	AK307477.1	None
mRNA	AY423727.1	AAS00490.1
mRNA	BC067223.1	AAH67223.1
mRNA	BG424022.1	None
mRNA	BG760757.1	None
mRNA	BM995301.1	None
mRNA	BU507758.1	None
mRNA	CD243986.1	None
mRNA	CR456775.1	CAG33056.1
mRNA	CR541714.1	CAG46515.1
mRNA	DA609380.1	None
mRNA	DB502157.1	None
mRNA	DC392310.1	None
mRNA	DC396757.1	None
mRNA	X02152.1	CAA26088.1