P00883 (ALDOA_RABIT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Fructose-bisphosphate aldolase A
EC=4.1.2.13

Alternative name(s):
Muscle-type aldolase

Gene names

Name:

ALDOA

Organism

Oryctolagus cuniculus (Rabbit) [Reference proteome]

Taxonomic identifier

9986 [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 › Lagomorpha › Leporidae › Oryctolagus

Protein attributes

Sequence length	364 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)

Function	Plays a key role in glycolysis and gluconeogenesis. In addition, may also function as scaffolding protein. Ref.14
Catalytic activity	D-fructose 1,6-bisphosphate = glycerone phosphate + D-glyceraldehyde 3-phosphate. Ref.16
Pathway	Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 4/4.
Subunit structure	Tetramer. Interacts with SNX9 and WAS. Ref.15 Ref.16
Post-translational modification	Asn-361 in form alpha is deaminated to Asp in form beta.
Miscellaneous	In vertebrates, three forms of this ubiquitous glycolytic enzyme are found, aldolase A in muscle, aldolase B in liver and aldolase C in brain. Alkylation of Arg-43 inactivates the enzyme.
Sequence similarities	Belongs to the class I fructose-bisphosphate aldolase family.

Ontologies

Keywords
Biological process	Glycolysis
Ligand	Schiff base
Molecular function	Lyase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	glycolysis Inferred from direct assay Ref.16. Source: UniProtKB protein homotetramerization Inferred from physical interaction Ref.16. Source: UniProtKB
Molecular_function	fructose-bisphosphate aldolase activity Inferred from direct assay Ref.16. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.2 Ref.3 Ref.4

Chain

2 – 364

363

Fructose-bisphosphate aldolase A

PRO_0000216938

Sites

Active site

188

1

Proton acceptor Ref.8 Ref.9

Active site

230

1

Schiff-base intermediate with dihydroxyacetone-P Ref.8 Ref.9

Binding site

43

1

Substrate

Binding site

304

1

Substrate

Site

73

1

Essential for substrate cleavage

Site

108

1

Essential for substrate cleavage

Site

147

1

Alkylation inactivates the enzyme

Site

362

1

Alkylation inactivates the enzyme; essential for the subsequent hydrolysis of the dihydroxyacetone Schiff base

Site

364

1

Necessary for preference for fructose 1,6-bisphosphate over fructose 1-phosphate

Amino acid modifications

Modified residue

9

1

Phosphothreonine By similarity

Modified residue

13

1

N6-acetyllysine By similarity

Modified residue

36

1

Phosphoserine By similarity

Modified residue

37

1

Phosphothreonine By similarity

Modified residue

39

1

Phosphoserine By similarity

Modified residue

42

1

N6-acetyllysine By similarity

Modified residue

46

1

Phosphoserine By similarity

Modified residue

65

1

Phosphothreonine By similarity

Modified residue

108

1

N6-acetyllysine By similarity

Modified residue

111

1

N6-malonyllysine By similarity

Modified residue

204

1

Phosphotyrosine By similarity

Modified residue

223

1

Phosphotyrosine By similarity

Modified residue

235

1

Phosphothreonine By similarity

Modified residue

241

1

Phosphothreonine By similarity

Modified residue

312

1

N6-malonyllysine By similarity

Modified residue

330

1

N6-acetyllysine By similarity

Modified residue

354

1

Phosphoserine By similarity

Modified residue

356

1

Phosphoserine By similarity

Modified residue

361

1

Deamidated asparagine; in form beta

Modified residue

364

1

Phosphotyrosine By similarity

Experimental info

Mutagenesis

35

1

E → A: Reduces activity 14-fold. Ref.12

Mutagenesis

43

1

R → A: Reduces activity 14-fold. Ref.12

Mutagenesis

129

1

D → V: Alters protein-protein interactions, leading to a dimeric protein.

Mutagenesis

147

1

K → A: Loss of activity. Ref.12

Mutagenesis

188

1

E → A: Reduces activity over 100-fold. Ref.13

Mutagenesis

188

1

E → Q: Reduces activity over 1000-fold. Ref.13

Mutagenesis

190

1

E → Q: Reduces activity 20-fold. Ref.13

Mutagenesis

230

1

K → M: Loss of activity. Ref.13

Mutagenesis

304

1

R → A: Reduces activity 400-fold. Ref.12

Sequence conflict

35

1

E → Q AA sequence Ref.4

Sequence conflict

274 – 276

3

GQS → SQE AA sequence Ref.6

Sequence conflict

276

1

S → E AA sequence Ref.6

Sequence conflict

294 – 296

3

KPW → WPK AA sequence Ref.6

Sequence conflict

354

1

S → R in CAA24246. Ref.7

Secondary structure

1

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364

Helix Strand Turn

Details...

Helix

10 – 23

14

Beta strand

29 – 33

5

Helix

37 – 45

9

Turn

46 – 48

3

Helix

53 – 64

12

Helix

68 – 70

3

Turn

71 – 73

3

Beta strand

74 – 79

6

Helix

81 – 84

4

Turn

89 – 91

3

Helix

94 – 99

6

Turn

100 – 102

3

Beta strand

104 – 108

5

Beta strand

113 – 115

3

Beta strand

119 – 121

3

Beta strand

123 – 125

3

Helix

131 – 140

10

Beta strand

145 – 152

8

Beta strand

155 – 157

3

Helix

161 – 180

20

Beta strand

184 – 191

8

Helix

199 – 219

21

Helix

224 – 226

3

Helix

246 – 258

13

Beta strand

267 – 270

4

Helix

277 – 289

13

Beta strand

290 – 292

3

Beta strand

296 – 303

8

Helix

304 – 314

11

Helix

318 – 320

3

Helix

321 – 338

18

Turn

339 – 341

3

Beta strand

345 – 347

3

Beta strand

349 – 352

4

Beta strand

358 – 360

3

Helix

361 – 363

3

Sequences

	Sequence		Length	Mass (Da)
	P00883 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: E61BCBC60F668324	FASTA	364	39,343
	10 20 30 40 50 60 MPHSHPALTP EQKKELSDIA HRIVAPGKGI LAADESTGSI AKRLQSIGTE NTEENRRFYR 70 80 90 100 110 120 QLLLTADDRV NPCIGGVILF HETLYQKADD GRPFPQVIKS KGGVVGIKVD KGVVPLAGTN 130 140 150 160 170 180 GETTTQGLDG LSERCAQYKK DGADFAKWRC VLKIGEHTPS ALAIMENANV LARYASICQQ 190 200 210 220 230 240 NGIVPIVEPE ILPDGDHDLK RCQYVTEKVL AAVYKALSDH HIYLEGTLLK PNMVTPGHAC 250 260 270 280 290 300 TQKYSHEEIA MATVTALRRT VPPAVTGVTF LSGGQSEEEA SINLNAINKC PLLKPWALTF 310 320 330 340 350 360 SYGRALQASA LKAWGGKKEN LKAAQEEYVK RALANSLACQ GKYTPSGQAG AAASESLFIS NHAY

References

[1]	"The complete nucleotide sequence for rabbit muscle aldolase A messenger RNA." Tolan D.R., Amsden A.B., Putney S.D., Urdea M.S., Penhoet E.E. J. Biol. Chem. 259:1127-1131(1984) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"The amino acid sequence of rabbit muscle aldolase." Sajgo M., Hajos G. Acta Biochim. Biophys. Acad. Sci. Hung. 9:239-241(1974) [PubMed] [Europe PMC] [Abstract] Cited for: PRELIMINARY PROTEIN SEQUENCE OF 2-364. Tissue: Muscle.
[3]	"Amino acid sequence of rabbit muscle aldolase and the structure of the active center." Lai C.-Y., Nakai N., Chang D. Science 183:1204-1206(1974) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-364. Tissue: Muscle.
[4]	"Studies on the structure of rabbit muscle aldolase. Ordering of the tryptic peptides; sequence of 164 amino acid residues in the NH2-terminal BrCN peptide." Nakai N., Chang D., Lai C.-Y. Arch. Biochem. Biophys. 166:347-357(1975) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-165.
[5]	"Extended amino acid sequences around the active-site lysine residue of class-I fructose 1,6-bisphosphate aldolases from rabbit muscle, sturgeon muscle, trout muscle and ox liver." Benfield P.A., Forcina B.G., Gibbons I., Perham R.N. Biochem. J. 183:429-444(1979) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 174-201, SEQUENCE REVISION.
[6]	"Studies on the structure of rabbit muscle aldolase. Determination of the primary structure of the COOH-terminal BrCN peptide; the complete sequence of the subunit polypeptide chain." Lai C.-Y. Arch. Biochem. Biophys. 166:358-368(1975) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 252-364, SEQUENCE REVISION.
[7]	"A new troponin T and cDNA clones for 13 different muscle proteins, found by shotgun sequencing." Putney S.D., Herlihy W.C., Schimmel P.R. Nature 302:718-721(1983) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 38-56 AND 350-364.
[8]	"Identification of the histidyl residue of rabbit muscle aldolase alkylated by N-bromoacetylethanolamine phosphate." Hartman F.C., Welch M.H. Biochem. Biophys. Res. Commun. 57:85-92(1974) [PubMed] [Europe PMC] [Abstract] Cited for: ACTIVE SITE.
[9]	"Affinity labeling of a previously undetected essential lysyl residue in class I fructose bisphosphate aldolase." Hartman F.C., Brown J.P. J. Biol. Chem. 251:3057-3062(1976) [PubMed] [Europe PMC] [Abstract] Cited for: ACTIVE SITE.
[10]	"Identification of the C-1-phosphate-binding arginine residue of rabbit-muscle aldolase. Isolation of 1,2-cyclohexanedione-labeled peptide by chemisorption chromatography." Patthy L., Varadi A., Thesz J., Kovacs K. Eur. J. Biochem. 99:309-313(1979) [PubMed] [Europe PMC] [Abstract] Cited for: SUBSTRATE-BINDING SITE.
[11]	"Product binding and role of the C-terminal region in class I D-fructose 1,6-bisphosphate aldolase." Blom N., Sygusch J. Nat. Struct. Biol. 4:36-39(1997) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
[12]	"Structure of a fructose-1,6-bis(phosphate) aldolase liganded to its natural substrate in a cleavage-defective mutant at 2.3 A." Choi K.H., Mazurkie A.S., Morris A.J., Utheza D., Tolan D.R., Allen K.N. Biochemistry 38:12655-12664(1999) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 3-345 IN COMPLEX WITH SUBSTRATE, MUTAGENESIS OF GLU-35; ARG-43; LYS-147 AND ARG-304.
[13]	"A conserved glutamate residue exhibits multifunctional catalytic roles in D-fructose-1,6-bisphosphate aldolases." Maurady A., Zdanov A., de Moissac D., Beaudry D., Sygusch J. J. Biol. Chem. 277:9474-9483(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.46 ANGSTROMS), MUTAGENESIS OF GLU-188; GLU-190 AND LYS-230.
[14]	"A hydrophobic pocket in the active site of glycolytic aldolase mediates interactions with Wiskott-Aldrich syndrome protein." St-Jean M., Izard T., Sygusch J. J. Biol. Chem. 282:14309-14315(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) IN COMPLEX WITH WAS, FUNCTION.
[15]	"Structure of a rabbit muscle fructose-1,6-bisphosphate aldolase A dimer variant." Sherawat M., Tolan D.R., Allen K.N. Acta Crystallogr. D 64:543-550(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 5-344 OF MUTANT VAL-129, SUBUNIT.
[16]	"Mechanism of aldolase control of sorting nexin 9 function in endocytosis." Rangarajan E.S., Park H., Fortin E., Sygusch J., Izard T. J. Biol. Chem. 285:11983-11990(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) IN COMPLEX WITH SNX9, INTERACTION WITH SNX9, SUBUNIT, CATALYTIC ACTIVITY.
+	Additional computationally mapped references.

Web resources

Worthington enzyme manual

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

K02300 mRNA. Translation: AAA31156.1.
V00876 mRNA. Translation: CAA24245.1.
V00877 mRNA. Translation: CAA24246.1.

PIR

ADRBA. A92444.

RefSeq

NP_001075707.1. NM_001082238.1.

UniGene

Ocu.864.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ADO	X-ray	1.90	A/B/C/D	2-364	[»]
1EWD	X-ray	2.46	A/B/C/D	2-364	[»]
1EWE	X-ray	2.60	A/B/C/D	2-364	[»]
1EX5	X-ray	2.20	A/B/C/D	2-364	[»]
1J4E	X-ray	2.65	A/B/C/D	2-363	[»]
1ZAH	X-ray	1.80	A/B/C/D	2-363	[»]
1ZAI	X-ray	1.76	A/B/C/D	2-363	[»]
1ZAJ	X-ray	1.89	A/B/C/D	2-363	[»]
1ZAL	X-ray	1.89	A/B/C/D	2-363	[»]
2OT0	X-ray	2.05	A/B/C/D	2-364	[»]
2OT1	X-ray	2.05	A/B/C/D	2-364	[»]
2QUT	X-ray	1.88	A/B/C/D	2-364	[»]
2QUU	X-ray	1.98	A/B/C/D	2-364	[»]
2QUV	X-ray	2.22	A/B/C/D	2-364	[»]
3B8D	X-ray	2.00	A/B/C/D	2-364	[»]
3BV4	X-ray	1.70	A	5-344	[»]
3DFN	X-ray	1.86	A/B/C/D	2-364	[»]
3DFO	X-ray	1.94	A/B/C/D	2-364	[»]
3DFP	X-ray	2.05	A/B/C/D	2-364	[»]
3DFQ	X-ray	1.82	A/B/C/D	2-364	[»]
3DFS	X-ray	2.03	A/B/C/D	2-364	[»]
3DFT	X-ray	1.94	A/B/C/D	2-364	[»]
3LGE	X-ray	2.20	A/B/C/D	2-364	[»]
3TU9	X-ray	2.09	A/B/C/D	2-364	[»]
6ALD	X-ray	2.30	A/B/C/D	2-364	[»]

ProteinModelPortal

P00883.

SMR

P00883. Positions 2-364.

ModBase

Search...

Protein-protein interaction databases

STRING

9986.ENSOCUP00000020204.

Proteomic databases

PRIDE

P00883.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSOCUT00000009869; ENSOCUP00000008499; ENSOCUG00000006329.

GeneID

100009055.

Organism-specific databases

CTD

226.

Phylogenomic databases

eggNOG

COG3588.

GeneTree

ENSGT00390000010235.

HOGENOM

HOG000220876.

HOVERGEN

HBG002386.

OrthoDB

EOG4X3H1J.

Enzyme and pathway databases

SABIO-RK

P00883.

UniPathway

UPA00109; UER00183.

Family and domain databases

Gene3D

3.20.20.70. 1 hit.

InterPro

IPR000741. Aldolase_I.
IPR013785. Aldolase_TIM.
[Graphical view]

PANTHER

PTHR11627. PTHR11627. 1 hit.

Pfam

PF00274. Glycolytic. 1 hit.
[Graphical view]

PROSITE

PS00158. ALDOLASE_CLASS_I. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P00883.

ChEMBL

CHEMBL4695.

EvolutionaryTrace

P00883.

Entry information

Entry name

ALDOA_RABIT

Accession

Primary (citable) accession number: P00883
Secondary accession number(s): Q28671

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 21, 1986
Last sequence update:	January 23, 2007
Last modified:	April 3, 2013
This is version 124 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program