Reviewed, UniProtKB/Swiss-Prot P05062 (ALDOB_HUMAN)

Names and origin

Protein names

Recommended name:
    Fructose-bisphosphate aldolase B
    EC=4.1.2.13
Alternative name(s):
    Liver-type aldolase

Gene names

Name:	ALDOB
Synonyms:	ALDB

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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)

Catalytic activity	D-fructose 1,6-bisphosphate = glycerone phosphate + D-glyceraldehyde 3-phosphate.
Pathway	Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 4/4.
Subunit structure	Homotetramer.
Involvement in disease	Defects in ALDOB are the cause of hereditary fructose intolerance (HFI) [MIM:229600]. HFI is an autosomal recessive disease that results in an inability to metabolize fructose and related sugars. Complete exclusion of fructose results in dramatic recovery; however, if not treated properly, HFI subjects suffer episodes of hypoglycemia, general ill condition, and risk of death the remainder of life.
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.
Sequence similarities	Belongs to the class I fructose-bisphosphate aldolase family.
Biophysicochemical properties	Kinetic parameters: KM=1.6 µM for fructose 1,6-bisphosphate KM=2.3 mM for fructose 1-phosphate

Ontologies

Keywords
Biological process	Glycolysis
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Ligand	Schiff base
Molecular function	Lyase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
Biological process	fructose metabolic process Ref.10 Traceable author statement. Source: ProtInc glycolysis Ref.10 Traceable author statement. Source: ProtInc
Cellular component	centriolar satellite Inferred from direct assay. Source: UniProtKB
Molecular function	fructose-bisphosphate aldolase activity Ref.10 Traceable author statement. Source: ProtInc protein binding Inferred from physical interaction. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Molecule processing

Initiator methionine

1

1

Removed

Chain

2 – 364

363

Fructose-bisphosphate aldolase B

Sites

Active site

188

1

Proton acceptor By similarity

Active site

230

1

Schiff-base intermediate with dihydroxyacetone-P

Binding site

56

1

Substrate

Binding site

147

1

Substrate

Site

364

1

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

Amino acid modifications

Modified residue

2

1

N-acetylalanine By similarity

Modified residue

36

1

Phosphoserine By similarity

Natural variations

Natural variant

74

1

I → T in HFI; affects proper folding.

Natural variant

120 – 121

2

Missing in HFI.

Natural variant

134

1

R → S: dbSNP rs10123355.

Natural variant

135

1

C → R in HFI; America; partial activity.

Natural variant

148

1

W → R in one subject with fructose intolerance; rare variant; America.

Natural variant

150

1

A → P in HFI; frequent mutation. dbSNP rs1800546.

Natural variant

175

1

A → D in HFI; frequent mutation.

Natural variant

185

1

P → R in HFI.

Natural variant

207

1

E → Q: dbSNP rs3739721.

Natural variant

222

1

V → F in HFI; affects proper folding.

Natural variant

229

1

L → P in HFI; affects proper folding.

Natural variant

257

1

L → P in HFI; Italy.

Natural variant

268

1

I → N: dbSNP rs10989495.

Natural variant

304

1

R → Q in HFI; 100-fold decrease in catalytic efficiency for substrates FBP and F1P.

Natural variant

304

1

R → W in HFI; Turkey; 4800-fold decrease in catalytic efficiency for FBP and inactive with F1P.

Natural variant

335

1

N → K in HFI; frequent mutation.

Natural variant

338

1

A → V in HFI; Turkey and South Europe.

Experimental info

Sequence conflict

54

1

E → D in AAA51691. Ref.5

Sequence conflict

250

1

A → D in CAA25072. Ref.7

Sequence conflict

278

1

E → D in BAA00125. Ref.4

Sequence conflict

309

1

S → V Ref.3

Sequence conflict

348

1

S → C in BAA00125. Ref.4

Secondary structure

1

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364

Helix Strand Turn

Details...

Helix

10 – 23

14

Beta strand

29 – 33

5

Helix

37 – 46

10

Helix

53 – 64

12

Helix

68 – 72

5

Beta strand

74 – 79

6

Helix

83 – 85

3

Helix

94 – 100

7

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

Helix

161 – 179

19

Turn

180 – 182

3

Beta strand

184 – 191

8

Helix

199 – 219

21

Helix

224 – 226

3

Helix

246 – 260

15

Beta strand

267 – 271

5

Helix

277 – 289

13

Beta strand

296 – 303

8

Helix

304 – 306

3

Helix

308 – 314

7

Helix

318 – 320

3

Helix

321 – 338

18

Turn

339 – 341

3

Helix

351 – 354

4

Sequences

	Sequence		Length	Mass (Da)
	P05062-1 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: DCE314E7AC5586CA	FASTA	364	39,473
	10 20 30 40 50 60 MAHRFPALTQ EQKKELSEIA QSIVANGKGI LAADESVGTM GNRLQRIKVE NTEENRRQFR 70 80 90 100 110 120 EILFSVDSSI NQSIGGVILF HETLYQKDSQ GKLFRNILKE KGIVVGIKLD QGGAPLAGTN 130 140 150 160 170 180 KETTIQGLDG LSERCAQYKK DGVDFGKWRA VLRIADQCPS SLAIQENANA LARYASICQQ 190 200 210 220 230 240 NGLVPIVEPE VIPDGDHDLE HCQYVTEKVL AAVYKALNDH HVYLEGTLLK PNMVTAGHAC 250 260 270 280 290 300 TKKYTPEQVA MATVTALHRT VPAAVPGICF LSGGMSEEDA TLNLNAINLC PLPKPWKLSF 310 320 330 340 350 360 SYGRALQASA LAAWGGKAAN KEATQEAFMK RAMANCQAAK GQYVHTGSSG AASTQSLFTA CYTY

References

[1]	"Isolation and nucleotide sequence of a full-length cDNA coding for aldolase B from human liver." Paolella G., Santamaria R., Izzo P., Costanzo P., Salvatore F. Nucleic Acids Res. 12:7401-7410(1984) [PubMed: 6548561] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Human aldolase isozyme gene: the structure of multispecies aldolase B mRNAs." Sakakibara M., Mukai T., Yatsuki H., Hori K. Nucleic Acids Res. 13:5055-5069(1985) [PubMed: 2410860] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Complete amino acid sequence for human aldolase B derived from cDNA and genomic clones." Rottmann W.H., Tolan D.R., Penhoet E.E. Proc. Natl. Acad. Sci. U.S.A. 81:2738-2742(1984) [PubMed: 6585824] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
[4]	"Human aldolase B gene: characterization of the genomic aldolase B gene and analysis of sequences required for multiple polyadenylations." Mukai T., Yatsuki H., Arai Y., Joh K., Matsuhashi S., Hori K. J. Biochem. 102:1043-1051(1987) [PubMed: 2830249] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[5]	"Characterization of the human aldolase B gene." Tolan D.R., Penhoet E.E. Mol. Biol. Med. 3:245-264(1986) [PubMed: 3016456] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"Construction and expression of human aldolase A and B expression plasmids in Escherichia coli host." Sakakibara M., Takahashi I., Takasaki Y., Mukai T., Hori K. Biochim. Biophys. Acta 1007:334-342(1989) [PubMed: 2649152] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-33 AND 357-364.
[7]	"Nucleotide sequence of a cDNA clone for human aldolase B." Besmond C., Dreyfus J.-C., Gregori C., Frain M., Zakin M.M., Sala Trepat J., Kahn A. Biochem. Biophys. Res. Commun. 117:601-609(1983) [PubMed: 6689266] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 238-364.
[8]	"The structure of human liver fructose-1,6-bisphosphate aldolase." Dalby A.R., Tolan D.R., Littlechild J.A. Acta Crystallogr. D 57:1526-1533(2001) [PubMed: 11679716] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS).
[9]	"Molecular basis of hereditary fructose intolerance: mutations and polymorphisms in the human aldolase B gene." Tolan D.R. Hum. Mutat. 6:210-218(1995) [PubMed: 8535439] [Abstract] Cited for: REVIEW ON VARIANTS.
[10]	"Catalytic deficiency of human aldolase B in hereditary fructose intolerance caused by a common missense mutation." Cross N.C.P., Tolan D.R., Cox T.M. Cell 53:881-885(1988) [PubMed: 3383242] [Abstract] Cited for: VARIANT HFI PRO-150.
[11]	"Molecular analysis of aldolase B genes in hereditary fructose intolerance." Cross N.C.P., de Franchis R., Sebastio G., Dazzo C., Tolan D.R., Gregori C., Odievre M., Vidailhet M., Romano V., Mascali G., Romano C., Musumeci S., Steinmann B., Gitzelmann R., Cox T.M. Lancet 335:306-309(1990) [PubMed: 1967768] [Abstract] Cited for: VARIANT HFI ASP-175.
[12]	"A partially active mutant aldolase B from a patient with hereditary fructose intolerance." Brooks C.C., Tolan D.R. FASEB J. 8:107-113(1994) [PubMed: 8299883] [Abstract] Cited for: VARIANT HFI ARG-135.
[13]	"Diverse mutations in the aldolase B gene that underlie the prevalence of hereditary fructose intolerance." Ali M., Cox T.M. Am. J. Hum. Genet. 56:1002-1005(1995) [PubMed: 7717389] [Abstract] Cited for: VARIANT ARG-148.
[14]	"Identification of a novel mutation (Leu 256-->Pro) in the human aldolase B gene associated with hereditary fructose intolerance." Ali M., Sebastio G., Cox T.M. Hum. Mol. Genet. 3:203-204(1994) [PubMed: 8162030] [Abstract] Cited for: VARIANT HFI PRO-257.
[15]	"A new aldolase B variant, N334K, is a common cause of hereditary fructose intolerance in Yugoslavia." Cross N.C.P., Stojanov L.M., Cox T.M. Nucleic Acids Res. 18:1925-1925(1990) [PubMed: 2336380] [Abstract] Cited for: VARIANT HFI LYS-335.
[16]	"Screening for hereditary fructose intolerance mutations by reverse dot-blot." Lau J., Tolan D.R. Mol. Cell. Probes 13:35-40(1999) [PubMed: 10024431] [Abstract] Cited for: VARIANTS HFI PRO-150; ASP-175; PRO-257; TRP-304; LYS-335 AND VAL-338.
[17]	"Functional and molecular modelling studies of two hereditary fructose intolerance-causing mutations at arginine 303 in human liver aldolase." Santamaria R., Esposito G., Vitagliano L., Race V., Paglionico I., Zancan L., Zagari A., Salvatore F. Biochem. J. 350:823-828(2000) [PubMed: 10970798] [Abstract] Cited for: VARIANTS HFI GLN-304 AND TRP-304, CHARACTERIZATION OF VARIANTS HFI GLN-304 AND TRP-304, KINETIC PARAMETERS.
[18]	"Molecular analysis of the aldolase B gene in patients with hereditary fructose intolerance from Spain." Sanchez-Gutierrez J.C., Benlloch T., Leal M.A., Samper B., Garcia-Ripoll I., Feliu J.E. J. Med. Genet. 39:E56-E56(2002) [PubMed: 12205126] [Abstract] Cited for: VARIANTS HFI PRO-150; ASP-175; ARG-185 AND LYS-335.
[19]	"Six novel alleles identified in Italian hereditary fructose intolerance patients enlarge the mutation spectrum of the aldolase B gene." Esposito G., Santamaria R., Vitagliano L., Ieno L., Viola A., Fiori L., Parenti G., Zancan L., Zagari A., Salvatore F. Hum. Mutat. 24:534-534(2004) [PubMed: 15532022] [Abstract] Cited for: VARIANTS HFI THR-74; 120-ASN-LYS-121 DEL; PRO-150; ASP-175; PHE-222; PRO-229; PRO-257; LYS-335 AND VAL-338, CHARACTERIZATION OF VARIANTS HFI THR-74; PHE-222 AND PRO-229.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

X02747 mRNA. Translation: CAA26526.1.
X01098 mRNA. Translation: CAA25572.1.
D00183 Genomic DNA. Translation: BAA00125.1.
M15656, M15657 Genomic DNA. Translation: AAA51691.1.
X00270 mRNA. Translation: CAA25072.1.

PIR

ADHUB. A41505.

RefSeq

NP_000026.2.

UniGene

Hs.530274

3D structure databases

PDBMSD

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1QO5	X-ray	2.50	A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R	2-364	[»]
1XDL	X-ray	3.00	A/B/C/D/W/X/Y/Z	1-364	[»]
1XDM	X-ray	3.00	A/B/C/D/W/X/Y/Z	1-364	[»]

ModBase

Search...

PTM databases

PhosphoSite