ALDOA
Available structures PDB Ortholog search:PDBeRCSB List of PDB id codes 1ALD,2ALD,4ALD
Identifiers
Aliases	ALDOA, ALDA, GSD12, HEL-S-87p, aldolase, fructose-bisphosphate A, Aldolase A
External IDs	OMIM:103850;MGI:87994;HomoloGene:141054;GeneCards:ALDOA;OMA:ALDOA - orthologs
Gene location (Human) Chr. Chromosome 16 (human)[1] Band 16p11.2 Start 30,064,164bp[1] End 30,070,457bp[1]
Gene location (Mouse) Chr. Chromosome 7 (mouse)[2] Band 7|7 F3 Start 126,394,406bp[2] End 126,399,923bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in gastrocnemius muscle muscle of thigh skeletal muscle tissue superior frontal gyrus apex of heart prefrontal cortex right frontal lobe primary visual cortex left ventricle right auricle Top expressed in medial head of gastrocnemius muscle ankle vastus lateralis muscle triceps brachii muscle sternocleidomastoid muscle temporal muscle digastric muscle masseter muscle tibialis anterior muscle knee joint More reference expression data BioGPS n/a
Gene ontology Molecular function cytoskeletal protein binding tubulin binding fructose binding protein binding catalytic activity lyase activity actin binding fructose-bisphosphate aldolase activity identical protein binding RNA binding cadherin binding Cellular component cytoplasm M band membrane I band extracellular region actin cytoskeleton extracellular exosome platelet alpha granule lumen nucleus extracellular space cytosol secretory granule lumen tertiary granule lumen ficolin-1-rich granule lumen sperm head Biological process gluconeogenesis glycolytic process muscle cell cellular homeostasis canonical glycolysis actin filament organization fructose metabolic process platelet degranulation fructose 1,6-bisphosphate metabolic process ATP biosynthetic process regulation of cell shape protein homotetramerization striated muscle contraction neutrophil degranulation binding of sperm to zona pellucida Sources:Amigo /QuickGO
Orthologs Species Human Mouse Entrez 226 11674 Ensembl ENSG00000149925 ENSMUSG00000030695 UniProt P04075 P05064 RefSeq (mRNA) NM_000034 NM_001127617 NM_001243175 NM_001243177 NM_184041 NM_184043 NM_001355562 NM_001355563 NM_001355564 NM_001355565 NM_001177307 NM_001177308 NM_007438 RefSeq (protein) NP_001121089 NP_001230106 NP_908930 NP_908932 NP_001170778 NP_001170779 NP_031464 Location (UCSC) Chr 16: 30.06 – 30.07 Mb Chr 7: 126.39 – 126.4 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Aldolase A (ALDOA, orALDA), also known as fructose-bisphosphate aldolase, is anenzyme that in humans is encoded by theALDOA gene on chromosome 16.

The protein encoded by this gene is aglycolytic enzyme that catalyzes the reversible conversion offructose-1,6-bisphosphate toglyceraldehyde 3-phosphate (G3P) anddihydroxyacetone phosphate (DHAP). Threealdolase isozymes (A, B, and C), encoded by three different genes, are differentially expressed during development. Aldolase A is found in the developing embryo and is produced in even greater amounts in adult muscle. Aldolase A expression is repressed in adult liver, kidney and intestine and similar toaldolase C levels in brain and other nervous tissue. Aldolase A deficiency has been associated withmyopathy andhemolytic anemia.Alternative splicing and alternative promoter usage results in multiple transcript variants. Relatedpseudogenes have been identified on chromosomes 3 and 10.^[5]

ALDOA is ahomotetramer and one of the three aldolase isozymes (A, B, and C), encoded by three different genes.^[6][7] TheALDOA gene contains 8exons and the5'UTR IB.^[7] Keyamino acids responsible for its catalytic function have been identified. Theresidue Tyr363 functions as the acid–base catalyst for protonating C3 of thesubstrate, while Lys146 is proposed to stabilize the negative charge of the resultingconjugate base of Tyr363 and the strained configuration of theC-terminal. Residue Glu187 participates in multiple functions, including FBP aldolase catalysis, acid–base catalysis during substrate binding,dehydration, and substrate cleavage.^[8] Though ALDOA localizes to the nucleus, it lacks any knownnuclear localization signals (NLS).^[9]

In mammalian aldolase, the key catalyticamino acid residues involved in the reaction arelysine andtyrosine. The tyrosine acts as an efficient hydrogen acceptor while the lysine covalently binds and stabilizes the intermediates. Manybacteria use twomagnesiumions in place of the lysine.^{[citation needed]}

β-D-fructose 1,6-phosphate	fructose-bisphosphate aldolase		D-glyceraldehyde 3-phosphate		dihydroxyacetone phosphate
				+

CompoundC05378 atKEGG Pathway Database.Enzyme4.1.2.13 atKEGG Pathway Database.CompoundC00111 atKEGG Pathway Database.CompoundC00118 atKEGG Pathway Database.

The numbering of the carbon atoms indicates the fate of the carbons according to their position in fructose 6-phosphate.

ALDOA is a key enzyme in the fourth step of glycolysis, as well as in the reverse pathwaygluconeogenesis. It catalyzes the reversible conversion of fructose-1,6-bisphosphate to glyceraldehydes-3-phosphate and dihydroxyacetone phosphate byaldol cleavage of the C3–C4 bond. As a result, it is a crucial player inATPbiosynthesis.^{[6][8][9][10][11]} ALDOA also contributes to other "moonlighting" functions such as muscle maintenance, regulation of cell shape and motility,striated musclecontraction,actincytoskeleton organization, and regulation of cell proliferation.^[6][9][10] ALDOA likely regulates actin cytoskeleton remodeling through interacting withcytohesin-2 (ARNO) and Arf6.^[10]

ALDOA is ubiquitously expressed in most tissues, though it is predominantly expressed in developing embryo and adult muscle.^[6][11] Inlymphocytes, ALDOA is the predominant aldolase isoform.^[11] Within the cell, ALDOA typicallylocalizes to thecytoplasm, but it can localize to thenucleus duringDNA synthesis of thecell cycle S phase. This nuclear localization is regulated by the proteinkinasesAKT andp38. It is suggested that the nucleus serves as a reservoir for ALDOA in low glucose conditions.^[9] ALDOA has also been found inmitochondria.^[11]

ALDOA is regulated by the energy metabolism substratesglucose,lactate, andglutamine.^[9] In humanmast cells (MCs), ALDOA has been observed to undergo post-translational regulation by proteintyrosinenitration, which may alter its relativeaffinity forFBP and/orIP3. This change then affects IP3 and PLCsignaling cascades in IgE-dependent responses.^[11]

Aldolase A (ALDOA) is highly expressed in multiple cancers, includinglung squamous cell carcinoma (LSCC),renal cancer, andhepatocellular carcinoma. It is proposed that ALDOA overexpression enhances glycolysis in these tumor cells, promoting their growth. In LSCC, its upregulation correlates withmetastasis and poor prognosis, while its downregulation reduces tumor cell motility andtumorigenesis. Thus, ALDOA could be a potential LSCCbiomarker and therapeutic drug target.^[6]

Aldolase A deficiency is a rare,autosomalrecessive disorder that is linked tohemolysis and accompanied by weakness, muscle pain, andmyopathy.^[7]

Click on genes, proteins and metabolites below to link to respective articles.^{[§ 1]}

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|alt=Glycolysis and Gluconeogenesisedit]]

Glycolysis and Gluconeogenesisedit

1. ^The interactive pathway map can be edited at WikiPathways:"GlycolysisGluconeogenesis_WP534".

Aldolase A has been shown tointeract with:

• PLD2,^[12]
• actin,^[11]
• GLUT4,^[13]
• phospholipase D2,^[13]
• light chain 8 ofdynein,^[13]
• erythrocyte anion exchanger Band 3 protein,^[13]
• ryanodine receptor,^[11]
• Cytohesin-2,^[10] and
• V-ATPase (vacuolar-type H+-ATPase).^[10]

• ALDOB
• ALDOC
• Fructose-bisphosphate aldolase

• http://pdbdev.sdsc.edu:48346/pdb/molecules/pdb50_5.html^{[permanent dead link‍]}
• Fructose-Bisphosphate+Aldolase at the U.S. National Library of MedicineMedical Subject Headings (MeSH)
• ALDOA
• EC4.1.2.13
• HumanALDOA genome location andALDOA gene details page in theUCSC Genome Browser.
• PDBe-KB provides an overview of all the structure information available in the PDB for Human Fructose-bisphosphate aldolase A

• Genes on human chromosome 16
• Enzymes
• Glycolysis

• Articles with short description
• Short description matches Wikidata
• All articles with unsourced statements
• Articles with unsourced statements from March 2023
• All articles with dead external links
• Articles with dead external links from October 2018
• Articles with permanently dead external links