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FLASH GENE

Symbol

LDHA

contributors: mct - updated : 11-05-2020

HGNC name	lactate dehydrogenase A
HGNC id	6535

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	14.04 kb     8 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

Y

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001165416 7 - 2102 NP_001158888 - 241 - 2005 16154111 NM_001135239 7 - 2052 NP_001128711 - 274 - 2005 16154111 NM_005566 8 - 2241 NP_005557 - 332 - 2005 16154111 NM_001165415 7 - 1762 NP_001158887 - 274 - 2005 16154111 NM_001165414 8 - 2323

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       highly Digestive esophagus       highly   liver       highly Nervous brain       highly Reproductive female system uterus cervix   highly Visual eye anterior segment cornea       eye retina       Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal   predominantly

cells

System Cell Pubmed Species Stage Rna symbol Visual cone photoreceptor Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

mono polymer

homomer , tetramer

HOMOLOGY

Homologene

FAMILY

lactate dehydrogenase family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,organelle,membrane
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus

basic FUNCTION	catalyzing the conversion of L-lactate and NAD to pyruvate and NADH in the final step of anaerobic glycolysis
	oxidative stress induces not only poly-ubiquitination but also mono-ubiquitination of LDHA, which may be involved in its lysosomal degradation during unloading
	may mediate tumor growth and metastasic effects in hepatocellular carcinoma (HCC)
	sperm without LDHC were still able to convert lactate to pyruvate as mediated by LDHA that is tightly bound to the fibrous sheath
	LDHA is critically important for sustaining the rapid angiogenesis of pulmonary microvascular endothelial cells
	LDHA is the master regulator of aerobic glycolysis; it actively reduces pyruvate and causes enhanced lactate levels in tumor tissues
	is indispensable for vascular smooth muscle cell proliferation and migration
	release of LDHA from degenerating neurons drives central nervous system (CNS) angiogenesis
	LDHA has a key role in aerobic glycolysis (the Warburg effect) through regeneration of the electron acceptor NAD+ and is widely regarded as a desirable target for cancer therapeutics
	key enzyme in glycolysis, that is highly expressed in a variety of tumors and catalyzes pyruvate to lactate
	LDHA has a higher affinity for pyruvate, preferentially converting pyruvate to lactate, and NADH to NAD+ in anaerobic conditions
	role of LDHA and LDHB to control apoptosis and autophagy in tumor cells

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

	anaerobic glycolysis, final step
	FOXM1-LDHA signaling functioned as a stimulator of glycolysis and promoted Gastric cancer progression

a component

KCNJ11 acts as an oncogene in hepatocellular carcinoma (HCC) though forming a complex with LDHA

INTERACTION

DNA

RNA

small molecule

protein	tyrosine phosphorylation of LDHA is important for NADH/NAD(+) redox homeostasis in cancer cells
	TNFSF11-induced LDHA, LDHB activation stimulates glycolytic and mitochondrial respiratory metabolism, facilitating mature osteoclast formation via osteoclast precursor fusion and NFATC1 signaling
	phosphorylation-induced activation of LDHA, an enzyme that catalyses the interconversion of pyruvate and lactate, promotes cancer cell invasion, anoikis resistance and tumour metastasis
	LDHC is required for LDHA expression in the sperm, and this unique functional interaction between LDH family members supports lactate dehydrogenase activity in the sperm
	TP53 negatively regulates LDHA expression by directly binding its promoter region
	interaction of MTA1 with MYC and recruitment of MTA1-MYC complex on to the LDHA promoter to regulate its transcription
	PCK1 reduces the stability of LDHA through posttranslational regulation and the effects of PCK1 on glucose metabolism, cell proliferation and metastasis are mediated via the inhibition of LDHA
	POU1F1 induces a metabolic reprogramming through LDHA regulation in breast tumor cells, modifying the phenotype of both cancer cells and fibroblasts to promote cancer progression

cell & other

REGULATION

induced by

a non-genomic pathway of estrogen action

ASSOCIATED DISORDERS

corresponding disease(s)

LDHAD

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in gastric cancer constitutional       loss of function inhibition of LDHA suppresses seizures constitutional     --other   increased LDHA/LDHB ratio causes high brain lactate levels, which, in turn, are predictive of aging phenotypes

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed cancer urinary   targeting the PCK1/LDHA pathway might be a new strategy to selectively inhibit tumor metabolism in in clear cell renal cell carcinoma neurology     LDHA is a molecular target for the development of new antiepileptic drugs cancer reproductive breast repression of LDHA induced by TP53 blocks tumor growth and invasion through downregulation of aerobic glycolysis in breast cance cancer lung   can be a potential target for lung adenocarcinoma (LUAD) treatment cardiovascular atheroma   LDHA is a potential therapeutic target to prevent vessel lumen constriction during the course of atherosclerosis and restenosis cancer reproductive prostate LDHA might be a potential therapeutic target in prostate cancer

ANIMAL & CELL MODELS