Full text data of ALDOA
ALDOA
(ALDA)
[Confidence: high (present in two of the MS resources)]
Fructose-bisphosphate aldolase A; 4.1.2.13 (Lung cancer antigen NY-LU-1; Muscle-type aldolase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Fructose-bisphosphate aldolase A; 4.1.2.13 (Lung cancer antigen NY-LU-1; Muscle-type aldolase)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00395757
IPI00395757 Fructose-bisphosphate aldolase A Fructose-bisphosphate aldolase A membrane 3 5 13 8 13 4 11 5 47 n/a n/a n/a n/a n/a n/a n/a n/a 15 9 9 Glycolisis, not mentioned n/a found at its expected molecular weight found at molecular weight
IPI00395757 Fructose-bisphosphate aldolase A Fructose-bisphosphate aldolase A membrane 3 5 13 8 13 4 11 5 47 n/a n/a n/a n/a n/a n/a n/a n/a 15 9 9 Glycolisis, not mentioned n/a found at its expected molecular weight found at molecular weight
UniProt
P04075
ID ALDOA_HUMAN Reviewed; 364 AA.
AC P04075; B4DXI7; Q6FH76; Q6FI10; Q96B15; Q9BWD9; Q9UCN2;
DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 171.
DE RecName: Full=Fructose-bisphosphate aldolase A;
DE EC=4.1.2.13;
DE AltName: Full=Lung cancer antigen NY-LU-1;
DE AltName: Full=Muscle-type aldolase;
GN Name=ALDOA; Synonyms=ALDA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=3840020;
RA Sakakibara M., Mukai T., Hori K.;
RT "Nucleotide sequence of a cDNA clone for human aldolase: a messenger
RT RNA in the liver.";
RL Biochem. Biophys. Res. Commun. 131:413-420(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Fibroblast;
RX PubMed=3030757; DOI=10.1111/j.1432-1033.1987.tb10984.x;
RA Izzo P., Costanzo P., Lupo A., Rippa E., Borghese A.M., Paolella G.,
RA Salvatore F.;
RT "A new human species of aldolase A mRNA from fibroblasts.";
RL Eur. J. Biochem. 164:9-13(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=3391172; DOI=10.1111/j.1432-1033.1988.tb14136.x;
RA Izzo P., Costanzo P., Lupo A., Rippa E., Paolella G., Salvatore F.;
RT "Human aldolase A gene. Structural organization and tissue-specific
RT expression by multiple promoters and alternate mRNA processing.";
RL Eur. J. Biochem. 174:569-578(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1999195; DOI=10.1111/j.1432-1033.1991.tb15766.x;
RA Mukai T., Arai Y., Yatsuki H., Joh K., Hori K.;
RT "An additional promoter functions in the human aldolase A gene, but
RT not in rat.";
RL Eur. J. Biochem. 195:781-787(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cervix, Eye, Lung, Testis, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-108 (ISOFORM 1).
RX PubMed=3441006; DOI=10.1016/0022-2836(87)90556-0;
RA Maire P., Gautron S., Hakim V., Gregori C., Mennecier F., Kahn A.;
RT "Characterization of three optional promoters in the 5' region of the
RT human aldolase A gene.";
RL J. Mol. Biol. 197:425-438(1987).
RN [11]
RP PROTEIN SEQUENCE OF 2-364.
RX PubMed=3355497;
RA Freemont P.S., Dunbar B., Fothergill-Gilmore L.A.;
RT "The complete amino acid sequence of human skeletal-muscle fructose-
RT bisphosphate aldolase.";
RL Biochem. J. 249:779-788(1988).
RN [12]
RP PROTEIN SEQUENCE OF 2-63 AND 148-358.
RX PubMed=6696436; DOI=10.1016/0003-9861(84)90075-4;
RA Freemont P.S., Dunbar B., Fothergill L.A.;
RT "Human skeletal-muscle aldolase: N-terminal sequence analysis of CNBr-
RT and o-iodosobenzoic acid-cleavage fragments.";
RL Arch. Biochem. Biophys. 228:342-352(1984).
RN [13]
RP PROTEIN SEQUENCE OF 2-22.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [14]
RP PROTEIN SEQUENCE OF 2-16.
RC TISSUE=Colon carcinoma;
RX PubMed=1353685; DOI=10.1016/0167-4889(92)90078-P;
RA Lee K.N., Maxwell M.D., Patterson M.K. Jr., Birckbichler P.J.,
RA Conway E.;
RT "Identification of transglutaminase substrates in HT29 colon cancer
RT cells: use of 5-(biotinamido)pentylamine as a transglutaminase-
RT specific probe.";
RL Biochim. Biophys. Acta 1136:12-16(1992).
RN [15]
RP PROTEIN SEQUENCE OF 2-13; 29-42; 44-56; 61-69; 88-99; 154-173; 244-258
RP AND 332-342, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [16]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 139-364 (ISOFORM 1/2).
RX PubMed=3674018;
RA Tolan D.R., Niclas J., Bruce B.D., Lebo R.V.;
RT "Evolutionary implications of the human aldolase-A, -B, -C, and -
RT pseudogene chromosome locations.";
RL Am. J. Hum. Genet. 41:907-924(1987).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-46, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-36 AND SER-39, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-42; LYS-108 AND LYS-330, AND
RP MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-36 AND SER-39, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [24]
RP MALONYLATION AT LYS-111 AND LYS-312.
RX PubMed=21908771; DOI=10.1074/mcp.M111.012658;
RA Peng C., Lu Z., Xie Z., Cheng Z., Chen Y., Tan M., Luo H., Zhang Y.,
RA He W., Yang K., Zwaans B.M., Tishkoff D., Ho L., Lombard D., He T.C.,
RA Dai J., Verdin E., Ye Y., Zhao Y.;
RT "The first identification of lysine malonylation substrates and its
RT regulatory enzyme.";
RL Mol. Cell. Proteomics 10:M111.012658.01-M111.012658.12(2011).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-39 AND SER-46, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
RX PubMed=2335208; DOI=10.1016/0014-5793(90)80211-Z;
RA Gamblin S.J., Cooper B., Millar J.R., Davies G.J., Littlechild J.A.,
RA Watson H.C.;
RT "The crystal structure of human muscle aldolase at 3.0-A resolution.";
RL FEBS Lett. 262:282-286(1990).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=2056525; DOI=10.1016/0022-2836(91)90650-U;
RA Gamblin S.J., Davies G.J., Grimes J.M., Jackson R.M.,
RA Littlechild J.A., Watson H.C.;
RT "Activity and specificity of human aldolases.";
RL J. Mol. Biol. 219:573-576(1991).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX PubMed=10048322;
RA Dalby A., Dauter Z., Littlechild J.A.;
RT "Crystal structure of human muscle aldolase complexed with fructose
RT 1,6-bisphosphate: mechanistic implications.";
RL Protein Sci. 8:291-297(1999).
RN [30]
RP VARIANT GSD12 GLY-129, AND CHARACTERIZATION OF VARIANT GSD12 GLY-129.
RX PubMed=2825199; DOI=10.1073/pnas.84.23.8623;
RA Kishi H., Mukai T., Hirono A., Fujii H., Miwa S., Hori K.;
RT "Human aldolase A deficiency associated with a hemolytic anemia:
RT thermolabile aldolase due to a single base mutation.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:8623-8627(1987).
RN [31]
RP CHARACTERIZATION OF VARIANT GSD12 GLY-129.
RX PubMed=2229018;
RA Takasaki Y., Takahashi I., Mukai T., Hori K.;
RT "Human aldolase A of a hemolytic anemia patient with Asp-128-->Gly
RT substitution: characteristics of an enzyme generated in E. coli
RT transfected with the expression plasmid pHAAD128G.";
RL J. Biochem. 108:153-157(1990).
RN [32]
RP VARIANT GSD12 LYS-207.
RX PubMed=8598869; DOI=10.1056/NEJM199604253341705;
RA Kreuder J., Borkhardt A., Repp R., Pekrun A., Goettsche B.,
RA Gottschalk U., Reichmann H., Schachenmayr W., Schlegel K., Lampert F.;
RT "Brief report: inherited metabolic myopathy and hemolysis due to a
RT mutation in aldolase A.";
RL N. Engl. J. Med. 334:1100-1104(1996).
RN [33]
RP VARIANT GSD12 TYR-339.
RX PubMed=14615364; DOI=10.1182/blood-2003-09-3160;
RA Yao D.C., Tolan D.R., Murray M.F., Harris D.J., Darras B.T., Geva A.,
RA Neufeld E.J.;
RT "Hemolytic anemia and severe rhabdomyolysis caused by compound
RT heterozygous mutations of the gene for erythrocyte/muscle isozyme of
RT aldolase, ALDOA(Arg303X/Cys338Tyr).";
RL Blood 103:2401-2403(2004).
RN [34]
RP VARIANT GSD12 SER-347, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP CHARACTERIZATION OF VARIANTS GSD12 LYS-207 AND SER-347.
RX PubMed=14766013; DOI=10.1042/BJ20031941;
RA Esposito G., Vitagliano L., Costanzo P., Borrelli L., Barone R.,
RA Pavone L., Izzo P., Zagari A., Salvatore F.;
RT "Human aldolase A natural mutants: relationship between flexibility of
RT the C-terminal region and enzyme function.";
RL Biochem. J. 380:51-56(2004).
CC -!- FUNCTION: Plays a key role in glycolysis and gluconeogenesis. In
CC addition, may also function as scaffolding protein (By
CC similarity).
CC -!- CATALYTIC ACTIVITY: D-fructose 1,6-bisphosphate = glycerone
CC phosphate + D-glyceraldehyde 3-phosphate.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=52 uM for fructose 1,6-bisphosphate (at 30 degrees Celsius);
CC Temperature dependence:
CC Thermal denaturation midpoint (Tm) is 54.4 degrees Celsius;
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC phosphate and glycerone phosphate from D-glucose: step 4/4.
CC -!- SUBUNIT: Homotetramer. Interacts with SNX9 and WAS (By
CC similarity).
CC -!- INTERACTION:
CC P12004:PCNA; NbExp=3; IntAct=EBI-709613, EBI-358311;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P04075-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P04075-2; Sequence=VSP_047261;
CC -!- DISEASE: Glycogen storage disease 12 (GSD12) [MIM:611881]: A
CC metabolic disorder associated with increased hepatic glycogen and
CC hemolytic anemia. It may lead to myopathy with exercise
CC intolerance and rhabdomyolysis. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: In vertebrates, three forms of this ubiquitous
CC glycolytic enzyme are found, aldolase A in muscle, aldolase B in
CC liver and aldolase C in brain.
CC -!- SIMILARITY: Belongs to the class I fructose-bisphosphate aldolase
CC family.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ALDOA";
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DR EMBL; M11560; AAA51690.1; -; mRNA.
DR EMBL; X05236; CAA28861.1; -; mRNA.
DR EMBL; X12447; CAA30979.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AK301993; BAG63399.1; -; mRNA.
DR EMBL; CR536528; CAG38765.1; -; mRNA.
DR EMBL; CR541880; CAG46678.1; -; mRNA.
DR EMBL; AC093512; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471238; EAW79933.1; -; Genomic_DNA.
DR EMBL; BC000367; AAH00367.2; -; mRNA.
DR EMBL; BC004333; AAH04333.1; -; mRNA.
DR EMBL; BC010660; AAH10660.1; -; mRNA.
DR EMBL; BC012880; AAH12880.1; -; mRNA.
DR EMBL; BC013614; AAH13614.1; -; mRNA.
DR EMBL; BC015888; AAH15888.1; -; mRNA.
DR EMBL; BC016170; AAH16170.1; -; mRNA.
DR EMBL; BC016800; AAH16800.1; -; mRNA.
DR EMBL; M21190; AAA51697.1; -; mRNA.
DR PIR; S14084; ADHUA.
DR RefSeq; NP_000025.1; NM_000034.3.
DR RefSeq; NP_001121089.1; NM_001127617.2.
DR RefSeq; NP_001230106.1; NM_001243177.1.
DR RefSeq; NP_908930.1; NM_184041.2.
DR RefSeq; NP_908932.1; NM_184043.2.
DR RefSeq; XP_005255227.1; XM_005255170.1.
DR UniGene; Hs.513490; -.
DR UniGene; Hs.732822; -.
DR PDB; 1ALD; X-ray; 2.00 A; A=2-364.
DR PDB; 2ALD; X-ray; 2.10 A; A=2-364.
DR PDB; 4ALD; X-ray; 2.80 A; A=2-364.
DR PDBsum; 1ALD; -.
DR PDBsum; 2ALD; -.
DR PDBsum; 4ALD; -.
DR ProteinModelPortal; P04075; -.
DR SMR; P04075; 2-364.
DR IntAct; P04075; 25.
DR MINT; MINT-4998828; -.
DR STRING; 9606.ENSP00000336927; -.
DR ChEMBL; CHEMBL2106; -.
DR PhosphoSite; P04075; -.
DR DMDM; 113606; -.
DR DOSAC-COBS-2DPAGE; P04075; -.
DR OGP; P04075; -.
DR REPRODUCTION-2DPAGE; IPI00465439; -.
DR REPRODUCTION-2DPAGE; P04075; -.
DR SWISS-2DPAGE; P04075; -.
DR UCD-2DPAGE; P04075; -.
DR PaxDb; P04075; -.
DR PRIDE; P04075; -.
DR DNASU; 226; -.
DR Ensembl; ENST00000338110; ENSP00000336927; ENSG00000149925.
DR Ensembl; ENST00000395248; ENSP00000378669; ENSG00000149925.
DR Ensembl; ENST00000412304; ENSP00000400452; ENSG00000149925.
DR Ensembl; ENST00000563060; ENSP00000455800; ENSG00000149925.
DR Ensembl; ENST00000564546; ENSP00000455917; ENSG00000149925.
DR Ensembl; ENST00000564595; ENSP00000457468; ENSG00000149925.
DR Ensembl; ENST00000566897; ENSP00000455724; ENSG00000149925.
DR Ensembl; ENST00000569545; ENSP00000455700; ENSG00000149925.
DR GeneID; 226; -.
DR KEGG; hsa:226; -.
DR UCSC; uc002dvw.3; human.
DR CTD; 226; -.
DR GeneCards; GC16P030064; -.
DR HGNC; HGNC:414; ALDOA.
DR HPA; CAB006252; -.
DR HPA; HPA004177; -.
DR MIM; 103850; gene.
DR MIM; 611881; phenotype.
DR neXtProt; NX_P04075; -.
DR Orphanet; 57; Glycogen storage disease due to aldolase A deficiency.
DR PharmGKB; PA24707; -.
DR eggNOG; COG3588; -.
DR HOVERGEN; HBG002386; -.
DR InParanoid; P04075; -.
DR KO; K01623; -.
DR OMA; PNMVIDG; -.
DR OrthoDB; EOG744T94; -.
DR PhylomeDB; P04075; -.
DR BioCyc; MetaCyc:HS07647-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_604; Hemostasis.
DR SABIO-RK; P04075; -.
DR UniPathway; UPA00109; UER00183.
DR EvolutionaryTrace; P04075; -.
DR GeneWiki; Aldolase_A; -.
DR GenomeRNAi; 226; -.
DR NextBio; 920; -.
DR PRO; PR:P04075; -.
DR ArrayExpress; P04075; -.
DR Bgee; P04075; -.
DR CleanEx; HS_ALDOA; -.
DR Genevestigator; P04075; -.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:BHF-UCL.
DR GO; GO:0031674; C:I band; TAS:BHF-UCL.
DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome.
DR GO; GO:0003779; F:actin binding; TAS:BHF-UCL.
DR GO; GO:0070061; F:fructose binding; IDA:BHF-UCL.
DR GO; GO:0004332; F:fructose-bisphosphate aldolase activity; IDA:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; TAS:BHF-UCL.
DR GO; GO:0015631; F:tubulin binding; TAS:BHF-UCL.
DR GO; GO:0007015; P:actin filament organization; TAS:BHF-UCL.
DR GO; GO:0006754; P:ATP biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0030388; P:fructose 1,6-bisphosphate metabolic process; IDA:BHF-UCL.
DR GO; GO:0006000; P:fructose metabolic process; IMP:BHF-UCL.
DR GO; GO:0006094; P:gluconeogenesis; TAS:Reactome.
DR GO; GO:0006096; P:glycolysis; IMP:BHF-UCL.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; IMP:BHF-UCL.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IDA:BHF-UCL.
DR GO; GO:0006941; P:striated muscle contraction; IMP:BHF-UCL.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR000741; Aldolase_I.
DR InterPro; IPR013785; Aldolase_TIM.
DR PANTHER; PTHR11627; PTHR11627; 1.
DR Pfam; PF00274; Glycolytic; 1.
DR PROSITE; PS00158; ALDOLASE_CLASS_I; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Direct protein sequencing; Disease mutation; Glycogen storage disease;
KW Glycolysis; Hereditary hemolytic anemia; Lyase; Phosphoprotein;
KW Polymorphism; Reference proteome; Schiff base.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 364 Fructose-bisphosphate aldolase A.
FT /FTId=PRO_0000216936.
FT ACT_SITE 188 188 Proton acceptor (By similarity).
FT ACT_SITE 230 230 Schiff-base intermediate with
FT dihydroxyacetone-P.
FT BINDING 56 56 Substrate.
FT BINDING 147 147 Substrate.
FT SITE 364 364 Necessary for preference for fructose
FT 1,6-bisphosphate over fructose 1-
FT phosphate.
FT MOD_RES 36 36 Phosphoserine.
FT MOD_RES 39 39 Phosphoserine.
FT MOD_RES 42 42 N6-acetyllysine.
FT MOD_RES 46 46 Phosphoserine.
FT MOD_RES 108 108 N6-acetyllysine.
FT MOD_RES 111 111 N6-malonyllysine.
FT MOD_RES 312 312 N6-malonyllysine.
FT MOD_RES 330 330 N6-acetyllysine.
FT VAR_SEQ 1 1 M -> MARRKPEGSSFNMTHLSMAMAFSFPPVASGQLHPQL
FT GNTQHQTELGKELATTSTM (in isoform 2).
FT /FTId=VSP_047261.
FT VARIANT 82 82 E -> Q (in dbSNP:rs11553107).
FT /FTId=VAR_048219.
FT VARIANT 129 129 D -> G (in GSD12; thermolabile).
FT /FTId=VAR_000550.
FT VARIANT 142 142 G -> V (in dbSNP:rs11553108).
FT /FTId=VAR_048220.
FT VARIANT 207 207 E -> K (in GSD12; reduces thermal
FT stability; 3-fold decrease in catalytic
FT efficiency mostly due to reduced
FT substrate affinity).
FT /FTId=VAR_044142.
FT VARIANT 339 339 C -> Y (in GSD12).
FT /FTId=VAR_044143.
FT VARIANT 347 347 G -> S (in GSD12; does not affect thermal
FT stability; 4-fold decrease in catalytic
FT efficiency due to reduced enzyme
FT activity; dbSNP:rs138824667).
FT /FTId=VAR_044144.
FT CONFLICT 180 180 Q -> R (in Ref. 6; CAG46678).
FT HELIX 10 23
FT STRAND 29 33
FT HELIX 37 46
FT HELIX 53 64
FT HELIX 68 73
FT STRAND 74 79
FT HELIX 83 85
FT HELIX 94 100
FT STRAND 104 108
FT STRAND 113 115
FT STRAND 119 121
FT STRAND 123 125
FT HELIX 131 140
FT STRAND 145 152
FT STRAND 155 157
FT HELIX 161 179
FT TURN 180 182
FT STRAND 184 191
FT HELIX 199 219
FT HELIX 224 226
FT HELIX 246 258
FT STRAND 267 270
FT HELIX 277 289
FT STRAND 296 303
FT HELIX 304 314
FT HELIX 318 320
FT HELIX 321 338
FT TURN 339 341
FT STRAND 348 350
SQ SEQUENCE 364 AA; 39420 MW; 0AAED80F755A7BE8 CRC64;
MPYQYPALTP EQKKELSDIA HRIVAPGKGI LAADESTGSI AKRLQSIGTE NTEENRRFYR
QLLLTADDRV NPCIGGVILF HETLYQKADD GRPFPQVIKS KGGVVGIKVD KGVVPLAGTN
GETTTQGLDG LSERCAQYKK DGADFAKWRC VLKIGEHTPS ALAIMENANV LARYASICQQ
NGIVPIVEPE ILPDGDHDLK RCQYVTEKVL AAVYKALSDH HIYLEGTLLK PNMVTPGHAC
TQKFSHEEIA MATVTALRRT VPPAVTGITF LSGGQSEEEA SINLNAINKC PLLKPWALTF
SYGRALQASA LKAWGGKKEN LKAAQEEYVK RALANSLACQ GKYTPSGQAG AAASESLFVS
NHAY
//
ID ALDOA_HUMAN Reviewed; 364 AA.
AC P04075; B4DXI7; Q6FH76; Q6FI10; Q96B15; Q9BWD9; Q9UCN2;
DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 171.
DE RecName: Full=Fructose-bisphosphate aldolase A;
DE EC=4.1.2.13;
DE AltName: Full=Lung cancer antigen NY-LU-1;
DE AltName: Full=Muscle-type aldolase;
GN Name=ALDOA; Synonyms=ALDA;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RX PubMed=3840020;
RA Sakakibara M., Mukai T., Hori K.;
RT "Nucleotide sequence of a cDNA clone for human aldolase: a messenger
RT RNA in the liver.";
RL Biochem. Biophys. Res. Commun. 131:413-420(1985).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Fibroblast;
RX PubMed=3030757; DOI=10.1111/j.1432-1033.1987.tb10984.x;
RA Izzo P., Costanzo P., Lupo A., Rippa E., Borghese A.M., Paolella G.,
RA Salvatore F.;
RT "A new human species of aldolase A mRNA from fibroblasts.";
RL Eur. J. Biochem. 164:9-13(1987).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=3391172; DOI=10.1111/j.1432-1033.1988.tb14136.x;
RA Izzo P., Costanzo P., Lupo A., Rippa E., Paolella G., Salvatore F.;
RT "Human aldolase A gene. Structural organization and tissue-specific
RT expression by multiple promoters and alternate mRNA processing.";
RL Eur. J. Biochem. 174:569-578(1988).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=1999195; DOI=10.1111/j.1432-1033.1991.tb15766.x;
RA Mukai T., Arai Y., Yatsuki H., Joh K., Hori K.;
RT "An additional promoter functions in the human aldolase A gene, but
RT not in rat.";
RL Eur. J. Biochem. 195:781-787(1991).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S.,
RA Neubert P., Kstrang K., Schatten R., Shen B., Henze S., Mar W.,
RA Korn B., Zuo D., Hu Y., LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15616553; DOI=10.1038/nature03187;
RA Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X.,
RA Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A.,
RA Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.,
RA Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L.,
RA Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A.,
RA Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D.,
RA Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J.,
RA Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M.,
RA Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I.,
RA Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W.,
RA Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A.,
RA Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S.,
RA Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J.,
RA Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D.,
RA Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L.,
RA Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A.,
RA Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L.,
RA Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N.,
RA Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M.,
RA Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L.,
RA Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D.,
RA Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P.,
RA Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M.,
RA Rubin E.M., Pennacchio L.A.;
RT "The sequence and analysis of duplication-rich human chromosome 16.";
RL Nature 432:988-994(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Cervix, Eye, Lung, Testis, and Uterus;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-108 (ISOFORM 1).
RX PubMed=3441006; DOI=10.1016/0022-2836(87)90556-0;
RA Maire P., Gautron S., Hakim V., Gregori C., Mennecier F., Kahn A.;
RT "Characterization of three optional promoters in the 5' region of the
RT human aldolase A gene.";
RL J. Mol. Biol. 197:425-438(1987).
RN [11]
RP PROTEIN SEQUENCE OF 2-364.
RX PubMed=3355497;
RA Freemont P.S., Dunbar B., Fothergill-Gilmore L.A.;
RT "The complete amino acid sequence of human skeletal-muscle fructose-
RT bisphosphate aldolase.";
RL Biochem. J. 249:779-788(1988).
RN [12]
RP PROTEIN SEQUENCE OF 2-63 AND 148-358.
RX PubMed=6696436; DOI=10.1016/0003-9861(84)90075-4;
RA Freemont P.S., Dunbar B., Fothergill L.A.;
RT "Human skeletal-muscle aldolase: N-terminal sequence analysis of CNBr-
RT and o-iodosobenzoic acid-cleavage fragments.";
RL Arch. Biochem. Biophys. 228:342-352(1984).
RN [13]
RP PROTEIN SEQUENCE OF 2-22.
RC TISSUE=Platelet;
RX PubMed=12665801; DOI=10.1038/nbt810;
RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A.,
RA Thomas G.R., Vandekerckhove J.;
RT "Exploring proteomes and analyzing protein processing by mass
RT spectrometric identification of sorted N-terminal peptides.";
RL Nat. Biotechnol. 21:566-569(2003).
RN [14]
RP PROTEIN SEQUENCE OF 2-16.
RC TISSUE=Colon carcinoma;
RX PubMed=1353685; DOI=10.1016/0167-4889(92)90078-P;
RA Lee K.N., Maxwell M.D., Patterson M.K. Jr., Birckbichler P.J.,
RA Conway E.;
RT "Identification of transglutaminase substrates in HT29 colon cancer
RT cells: use of 5-(biotinamido)pentylamine as a transglutaminase-
RT specific probe.";
RL Biochim. Biophys. Acta 1136:12-16(1992).
RN [15]
RP PROTEIN SEQUENCE OF 2-13; 29-42; 44-56; 61-69; 88-99; 154-173; 244-258
RP AND 332-342, AND MASS SPECTROMETRY.
RC TISSUE=Brain, Cajal-Retzius cell, and Fetal brain cortex;
RA Lubec G., Vishwanath V., Chen W.-Q., Sun Y.;
RL Submitted (DEC-2008) to UniProtKB.
RN [16]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 139-364 (ISOFORM 1/2).
RX PubMed=3674018;
RA Tolan D.R., Niclas J., Bruce B.D., Lebo R.V.;
RT "Evolutionary implications of the human aldolase-A, -B, -C, and -
RT pseudogene chromosome locations.";
RL Am. J. Hum. Genet. 41:907-924(1987).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-46, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P.,
RA Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in
RT signaling networks.";
RL Cell 127:635-648(2006).
RN [18]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [19]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-36 AND SER-39, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [21]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-42; LYS-108 AND LYS-330, AND
RP MASS SPECTROMETRY.
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA Walther T.C., Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-36 AND SER-39, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [23]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [24]
RP MALONYLATION AT LYS-111 AND LYS-312.
RX PubMed=21908771; DOI=10.1074/mcp.M111.012658;
RA Peng C., Lu Z., Xie Z., Cheng Z., Chen Y., Tan M., Luo H., Zhang Y.,
RA He W., Yang K., Zwaans B.M., Tishkoff D., Ho L., Lombard D., He T.C.,
RA Dai J., Verdin E., Ye Y., Zhao Y.;
RT "The first identification of lysine malonylation substrates and its
RT regulatory enzyme.";
RL Mol. Cell. Proteomics 10:M111.012658.01-M111.012658.12(2011).
RN [25]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-39 AND SER-46, AND MASS
RP SPECTROMETRY.
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [26]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [27]
RP X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS).
RX PubMed=2335208; DOI=10.1016/0014-5793(90)80211-Z;
RA Gamblin S.J., Cooper B., Millar J.R., Davies G.J., Littlechild J.A.,
RA Watson H.C.;
RT "The crystal structure of human muscle aldolase at 3.0-A resolution.";
RL FEBS Lett. 262:282-286(1990).
RN [28]
RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS).
RX PubMed=2056525; DOI=10.1016/0022-2836(91)90650-U;
RA Gamblin S.J., Davies G.J., Grimes J.M., Jackson R.M.,
RA Littlechild J.A., Watson H.C.;
RT "Activity and specificity of human aldolases.";
RL J. Mol. Biol. 219:573-576(1991).
RN [29]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS).
RX PubMed=10048322;
RA Dalby A., Dauter Z., Littlechild J.A.;
RT "Crystal structure of human muscle aldolase complexed with fructose
RT 1,6-bisphosphate: mechanistic implications.";
RL Protein Sci. 8:291-297(1999).
RN [30]
RP VARIANT GSD12 GLY-129, AND CHARACTERIZATION OF VARIANT GSD12 GLY-129.
RX PubMed=2825199; DOI=10.1073/pnas.84.23.8623;
RA Kishi H., Mukai T., Hirono A., Fujii H., Miwa S., Hori K.;
RT "Human aldolase A deficiency associated with a hemolytic anemia:
RT thermolabile aldolase due to a single base mutation.";
RL Proc. Natl. Acad. Sci. U.S.A. 84:8623-8627(1987).
RN [31]
RP CHARACTERIZATION OF VARIANT GSD12 GLY-129.
RX PubMed=2229018;
RA Takasaki Y., Takahashi I., Mukai T., Hori K.;
RT "Human aldolase A of a hemolytic anemia patient with Asp-128-->Gly
RT substitution: characteristics of an enzyme generated in E. coli
RT transfected with the expression plasmid pHAAD128G.";
RL J. Biochem. 108:153-157(1990).
RN [32]
RP VARIANT GSD12 LYS-207.
RX PubMed=8598869; DOI=10.1056/NEJM199604253341705;
RA Kreuder J., Borkhardt A., Repp R., Pekrun A., Goettsche B.,
RA Gottschalk U., Reichmann H., Schachenmayr W., Schlegel K., Lampert F.;
RT "Brief report: inherited metabolic myopathy and hemolysis due to a
RT mutation in aldolase A.";
RL N. Engl. J. Med. 334:1100-1104(1996).
RN [33]
RP VARIANT GSD12 TYR-339.
RX PubMed=14615364; DOI=10.1182/blood-2003-09-3160;
RA Yao D.C., Tolan D.R., Murray M.F., Harris D.J., Darras B.T., Geva A.,
RA Neufeld E.J.;
RT "Hemolytic anemia and severe rhabdomyolysis caused by compound
RT heterozygous mutations of the gene for erythrocyte/muscle isozyme of
RT aldolase, ALDOA(Arg303X/Cys338Tyr).";
RL Blood 103:2401-2403(2004).
RN [34]
RP VARIANT GSD12 SER-347, BIOPHYSICOCHEMICAL PROPERTIES, AND
RP CHARACTERIZATION OF VARIANTS GSD12 LYS-207 AND SER-347.
RX PubMed=14766013; DOI=10.1042/BJ20031941;
RA Esposito G., Vitagliano L., Costanzo P., Borrelli L., Barone R.,
RA Pavone L., Izzo P., Zagari A., Salvatore F.;
RT "Human aldolase A natural mutants: relationship between flexibility of
RT the C-terminal region and enzyme function.";
RL Biochem. J. 380:51-56(2004).
CC -!- FUNCTION: Plays a key role in glycolysis and gluconeogenesis. In
CC addition, may also function as scaffolding protein (By
CC similarity).
CC -!- CATALYTIC ACTIVITY: D-fructose 1,6-bisphosphate = glycerone
CC phosphate + D-glyceraldehyde 3-phosphate.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=52 uM for fructose 1,6-bisphosphate (at 30 degrees Celsius);
CC Temperature dependence:
CC Thermal denaturation midpoint (Tm) is 54.4 degrees Celsius;
CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-
CC phosphate and glycerone phosphate from D-glucose: step 4/4.
CC -!- SUBUNIT: Homotetramer. Interacts with SNX9 and WAS (By
CC similarity).
CC -!- INTERACTION:
CC P12004:PCNA; NbExp=3; IntAct=EBI-709613, EBI-358311;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P04075-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P04075-2; Sequence=VSP_047261;
CC -!- DISEASE: Glycogen storage disease 12 (GSD12) [MIM:611881]: A
CC metabolic disorder associated with increased hepatic glycogen and
CC hemolytic anemia. It may lead to myopathy with exercise
CC intolerance and rhabdomyolysis. Note=The disease is caused by
CC mutations affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: In vertebrates, three forms of this ubiquitous
CC glycolytic enzyme are found, aldolase A in muscle, aldolase B in
CC liver and aldolase C in brain.
CC -!- SIMILARITY: Belongs to the class I fructose-bisphosphate aldolase
CC family.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/ALDOA";
CC -----------------------------------------------------------------------
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CC Distributed under the Creative Commons Attribution-NoDerivs License
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DR EMBL; M11560; AAA51690.1; -; mRNA.
DR EMBL; X05236; CAA28861.1; -; mRNA.
DR EMBL; X12447; CAA30979.1; ALT_SEQ; Genomic_DNA.
DR EMBL; AK301993; BAG63399.1; -; mRNA.
DR EMBL; CR536528; CAG38765.1; -; mRNA.
DR EMBL; CR541880; CAG46678.1; -; mRNA.
DR EMBL; AC093512; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471238; EAW79933.1; -; Genomic_DNA.
DR EMBL; BC000367; AAH00367.2; -; mRNA.
DR EMBL; BC004333; AAH04333.1; -; mRNA.
DR EMBL; BC010660; AAH10660.1; -; mRNA.
DR EMBL; BC012880; AAH12880.1; -; mRNA.
DR EMBL; BC013614; AAH13614.1; -; mRNA.
DR EMBL; BC015888; AAH15888.1; -; mRNA.
DR EMBL; BC016170; AAH16170.1; -; mRNA.
DR EMBL; BC016800; AAH16800.1; -; mRNA.
DR EMBL; M21190; AAA51697.1; -; mRNA.
DR PIR; S14084; ADHUA.
DR RefSeq; NP_000025.1; NM_000034.3.
DR RefSeq; NP_001121089.1; NM_001127617.2.
DR RefSeq; NP_001230106.1; NM_001243177.1.
DR RefSeq; NP_908930.1; NM_184041.2.
DR RefSeq; NP_908932.1; NM_184043.2.
DR RefSeq; XP_005255227.1; XM_005255170.1.
DR UniGene; Hs.513490; -.
DR UniGene; Hs.732822; -.
DR PDB; 1ALD; X-ray; 2.00 A; A=2-364.
DR PDB; 2ALD; X-ray; 2.10 A; A=2-364.
DR PDB; 4ALD; X-ray; 2.80 A; A=2-364.
DR PDBsum; 1ALD; -.
DR PDBsum; 2ALD; -.
DR PDBsum; 4ALD; -.
DR ProteinModelPortal; P04075; -.
DR SMR; P04075; 2-364.
DR IntAct; P04075; 25.
DR MINT; MINT-4998828; -.
DR STRING; 9606.ENSP00000336927; -.
DR ChEMBL; CHEMBL2106; -.
DR PhosphoSite; P04075; -.
DR DMDM; 113606; -.
DR DOSAC-COBS-2DPAGE; P04075; -.
DR OGP; P04075; -.
DR REPRODUCTION-2DPAGE; IPI00465439; -.
DR REPRODUCTION-2DPAGE; P04075; -.
DR SWISS-2DPAGE; P04075; -.
DR UCD-2DPAGE; P04075; -.
DR PaxDb; P04075; -.
DR PRIDE; P04075; -.
DR DNASU; 226; -.
DR Ensembl; ENST00000338110; ENSP00000336927; ENSG00000149925.
DR Ensembl; ENST00000395248; ENSP00000378669; ENSG00000149925.
DR Ensembl; ENST00000412304; ENSP00000400452; ENSG00000149925.
DR Ensembl; ENST00000563060; ENSP00000455800; ENSG00000149925.
DR Ensembl; ENST00000564546; ENSP00000455917; ENSG00000149925.
DR Ensembl; ENST00000564595; ENSP00000457468; ENSG00000149925.
DR Ensembl; ENST00000566897; ENSP00000455724; ENSG00000149925.
DR Ensembl; ENST00000569545; ENSP00000455700; ENSG00000149925.
DR GeneID; 226; -.
DR KEGG; hsa:226; -.
DR UCSC; uc002dvw.3; human.
DR CTD; 226; -.
DR GeneCards; GC16P030064; -.
DR HGNC; HGNC:414; ALDOA.
DR HPA; CAB006252; -.
DR HPA; HPA004177; -.
DR MIM; 103850; gene.
DR MIM; 611881; phenotype.
DR neXtProt; NX_P04075; -.
DR Orphanet; 57; Glycogen storage disease due to aldolase A deficiency.
DR PharmGKB; PA24707; -.
DR eggNOG; COG3588; -.
DR HOVERGEN; HBG002386; -.
DR InParanoid; P04075; -.
DR KO; K01623; -.
DR OMA; PNMVIDG; -.
DR OrthoDB; EOG744T94; -.
DR PhylomeDB; P04075; -.
DR BioCyc; MetaCyc:HS07647-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR Reactome; REACT_604; Hemostasis.
DR SABIO-RK; P04075; -.
DR UniPathway; UPA00109; UER00183.
DR EvolutionaryTrace; P04075; -.
DR GeneWiki; Aldolase_A; -.
DR GenomeRNAi; 226; -.
DR NextBio; 920; -.
DR PRO; PR:P04075; -.
DR ArrayExpress; P04075; -.
DR Bgee; P04075; -.
DR CleanEx; HS_ALDOA; -.
DR Genevestigator; P04075; -.
DR GO; GO:0015629; C:actin cytoskeleton; IDA:BHF-UCL.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0070062; C:extracellular vesicular exosome; IDA:BHF-UCL.
DR GO; GO:0031674; C:I band; TAS:BHF-UCL.
DR GO; GO:0031093; C:platelet alpha granule lumen; TAS:Reactome.
DR GO; GO:0003779; F:actin binding; TAS:BHF-UCL.
DR GO; GO:0070061; F:fructose binding; IDA:BHF-UCL.
DR GO; GO:0004332; F:fructose-bisphosphate aldolase activity; IDA:BHF-UCL.
DR GO; GO:0042802; F:identical protein binding; TAS:BHF-UCL.
DR GO; GO:0015631; F:tubulin binding; TAS:BHF-UCL.
DR GO; GO:0007015; P:actin filament organization; TAS:BHF-UCL.
DR GO; GO:0006754; P:ATP biosynthetic process; IMP:BHF-UCL.
DR GO; GO:0030388; P:fructose 1,6-bisphosphate metabolic process; IDA:BHF-UCL.
DR GO; GO:0006000; P:fructose metabolic process; IMP:BHF-UCL.
DR GO; GO:0006094; P:gluconeogenesis; TAS:Reactome.
DR GO; GO:0006096; P:glycolysis; IMP:BHF-UCL.
DR GO; GO:0046716; P:muscle cell cellular homeostasis; IMP:BHF-UCL.
DR GO; GO:0030168; P:platelet activation; TAS:Reactome.
DR GO; GO:0002576; P:platelet degranulation; TAS:Reactome.
DR GO; GO:0051289; P:protein homotetramerization; ISS:UniProtKB.
DR GO; GO:0008360; P:regulation of cell shape; IDA:BHF-UCL.
DR GO; GO:0006941; P:striated muscle contraction; IMP:BHF-UCL.
DR Gene3D; 3.20.20.70; -; 1.
DR InterPro; IPR000741; Aldolase_I.
DR InterPro; IPR013785; Aldolase_TIM.
DR PANTHER; PTHR11627; PTHR11627; 1.
DR Pfam; PF00274; Glycolytic; 1.
DR PROSITE; PS00158; ALDOLASE_CLASS_I; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Direct protein sequencing; Disease mutation; Glycogen storage disease;
KW Glycolysis; Hereditary hemolytic anemia; Lyase; Phosphoprotein;
KW Polymorphism; Reference proteome; Schiff base.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 364 Fructose-bisphosphate aldolase A.
FT /FTId=PRO_0000216936.
FT ACT_SITE 188 188 Proton acceptor (By similarity).
FT ACT_SITE 230 230 Schiff-base intermediate with
FT dihydroxyacetone-P.
FT BINDING 56 56 Substrate.
FT BINDING 147 147 Substrate.
FT SITE 364 364 Necessary for preference for fructose
FT 1,6-bisphosphate over fructose 1-
FT phosphate.
FT MOD_RES 36 36 Phosphoserine.
FT MOD_RES 39 39 Phosphoserine.
FT MOD_RES 42 42 N6-acetyllysine.
FT MOD_RES 46 46 Phosphoserine.
FT MOD_RES 108 108 N6-acetyllysine.
FT MOD_RES 111 111 N6-malonyllysine.
FT MOD_RES 312 312 N6-malonyllysine.
FT MOD_RES 330 330 N6-acetyllysine.
FT VAR_SEQ 1 1 M -> MARRKPEGSSFNMTHLSMAMAFSFPPVASGQLHPQL
FT GNTQHQTELGKELATTSTM (in isoform 2).
FT /FTId=VSP_047261.
FT VARIANT 82 82 E -> Q (in dbSNP:rs11553107).
FT /FTId=VAR_048219.
FT VARIANT 129 129 D -> G (in GSD12; thermolabile).
FT /FTId=VAR_000550.
FT VARIANT 142 142 G -> V (in dbSNP:rs11553108).
FT /FTId=VAR_048220.
FT VARIANT 207 207 E -> K (in GSD12; reduces thermal
FT stability; 3-fold decrease in catalytic
FT efficiency mostly due to reduced
FT substrate affinity).
FT /FTId=VAR_044142.
FT VARIANT 339 339 C -> Y (in GSD12).
FT /FTId=VAR_044143.
FT VARIANT 347 347 G -> S (in GSD12; does not affect thermal
FT stability; 4-fold decrease in catalytic
FT efficiency due to reduced enzyme
FT activity; dbSNP:rs138824667).
FT /FTId=VAR_044144.
FT CONFLICT 180 180 Q -> R (in Ref. 6; CAG46678).
FT HELIX 10 23
FT STRAND 29 33
FT HELIX 37 46
FT HELIX 53 64
FT HELIX 68 73
FT STRAND 74 79
FT HELIX 83 85
FT HELIX 94 100
FT STRAND 104 108
FT STRAND 113 115
FT STRAND 119 121
FT STRAND 123 125
FT HELIX 131 140
FT STRAND 145 152
FT STRAND 155 157
FT HELIX 161 179
FT TURN 180 182
FT STRAND 184 191
FT HELIX 199 219
FT HELIX 224 226
FT HELIX 246 258
FT STRAND 267 270
FT HELIX 277 289
FT STRAND 296 303
FT HELIX 304 314
FT HELIX 318 320
FT HELIX 321 338
FT TURN 339 341
FT STRAND 348 350
SQ SEQUENCE 364 AA; 39420 MW; 0AAED80F755A7BE8 CRC64;
MPYQYPALTP EQKKELSDIA HRIVAPGKGI LAADESTGSI AKRLQSIGTE NTEENRRFYR
QLLLTADDRV NPCIGGVILF HETLYQKADD GRPFPQVIKS KGGVVGIKVD KGVVPLAGTN
GETTTQGLDG LSERCAQYKK DGADFAKWRC VLKIGEHTPS ALAIMENANV LARYASICQQ
NGIVPIVEPE ILPDGDHDLK RCQYVTEKVL AAVYKALSDH HIYLEGTLLK PNMVTPGHAC
TQKFSHEEIA MATVTALRRT VPPAVTGITF LSGGQSEEEA SINLNAINKC PLLKPWALTF
SYGRALQASA LKAWGGKKEN LKAAQEEYVK RALANSLACQ GKYTPSGQAG AAASESLFVS
NHAY
//
MIM
103850
*RECORD*
*FIELD* NO
103850
*FIELD* TI
*103850 ALDOLASE A, FRUCTOSE-BISPHOSPHATE; ALDOA
;;FRUCTOSE-1,6-BISPHOSPHATE ALDOLASE A;;
read moreALDOLASE A; ALDA;;
ALDOLASE 1;;
FRUCTOALDOLASE A
*FIELD* TX
DESCRIPTION
Fructose-1,6-bisphosphate aldolase (EC 4.1.2.13) is a glycolytic enzyme
that catalyzes the reversible conversion of fructose-1,6-bisphosphate to
glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. The enzyme is
a tetramer of identical 40-kD subunits. Vertebrates have 3 aldolase
isozymes, aldolases A, B (ALDOB; 612724), and C (ALDOC; 103870), which
are distinguished by their electrophoretic and catalytic properties. The
sequence of the aldolases around the active-site lysine is highly
conserved in evolution. Mammalian tissues express aldolase isozymes in a
well-characterized pattern. Developing embryo produces aldolase A, which
continues to be expressed in many adult tissues, sometimes at much
higher levels than in embryo. In adult muscle, aldolase A can be as much
as 5% of total cellular protein. In adult liver, kidney, and intestine,
aldolase A expression is repressed and aldolase B is produced. In brain
and other nervous tissue, aldolase A and C are expressed about equally.
In transformed liver cells, aldolase A replaces aldolase B (Rottmann et
al., 1984).
CLONING
Electrophoretic variants of fructoaldolase were reported by Charlesworth
(1972).
Sakakibara et al. (1985) cloned aldolase A from a human liver cDNA
library. The deduced protein contains 363 amino acids. RNA blot analysis
revealed a 1.6-kb ALDOA mRNA in skeletal muscle and a 1.7-kb ALDOA mRNA
in liver and placenta.
Freemont et al. (1988) presented the complete amino acid sequence of
human skeletal muscle fructose-bisphosphate aldolase, comprising 363
residues.
GENE STRUCTURE
Izzo et al. (1988) found that the ALDOA gene spans 7.5 kb and contains
12 exons. It occurs as a single copy per haploid human genome. Eight
exons containing the coding sequence were common to all mRNAs extracted
from several mammalian sources. Four additional exons were identified in
the 5-prime UTR: the first was contained in the ubiquitous mRNA, the
second in the muscle-specific mRNA, and the third and fourth in a minor
mRNA in human liver. S(1)-nuclease-protection analysis of the 5-prime
end of mRNA from cultured fibroblasts, muscle, and hepatoma cell lines
revealed 4 different transcription initiation sites. The presence of
conventional sequences for 4 eukaryotic promoters was also demonstrated.
The nucleotide similarities in the coding region and the intron-exon
organization of aldolases A, B, and C confirmed that they arose from a
common ancestral gene, with aldolase B diverging first.
MAPPING
Harris (1974) concluded that 3 loci determine aldolase. Cohen-Haguenauer
et al. (1985) assigned aldolase A to chromosome 16, whereas Kukita et
al. (1985) assigned it to chromosome 22. However, Kukita et al. (1987)
mapped the ALDOA gene to chromosome 16 by 3 different methods: molecular
hybridization to hybrid cell DNA, molecular hybridization to DNA of
sorted metaphase chromosomes, and in situ hybridization. In situ
hybridization indicated that the gene is located on the chromosome
16q22-q24 band. Serero et al. (1988) also assigned the aldolase A gene
to chromosome 16 by Southern blot analysis of human genomic DNA with a
cDNA probe. Aldolase A pseudogenes were found on chromosomes 3 and 10.
The map location of the 3 aldolase genes and the aldolase pseudogene
(see 612724) is of considerable interest from the point of view of
chromosome evolution. The 4 genes are found on 2 pairs of
morphologically similar chromosomes, 9 and 10, and 16 and 17. These
homeologous (i.e., of similar origin) chromosome pairs may have arisen
from 1 or 2 tetraploidization events (Comings, 1972; Ohno, 1973). As
predicted by the chromosomal locations, the coding sequences of the
expressed aldolase A and C genes on chromosomes 16 and 17, respectively,
are more homologous to each other than either of them is to the
expressed aldolase B gene on chromosome 9.
Amberger (2008) mapped the ALDOA gene to chromosome 16p11.2 based on an
alignment of the ALDOA sequence (GenBank GENBANK M11560) with the
genomic sequence (build 36.2).
MOLECULAR GENETICS
Kishi et al. (1987) studied a patient with red cell aldolase deficiency,
or glycogen storage disease XII (GSD12; 611881), and identified a
mutation in the ALDOA gene that resulted in an asp128-to-gly (D128G;
103850.0001) substitution in the protein. The patient's enzyme from red
cells and from cultured lymphoblastoid cells was highly thermolabile,
and the enzyme expressed in E. coli was likewise thermolabile. The
parents had intermediate levels of red cell aldolase A. Southern blot
analysis of genomic DNA showed that the patient was homozygous for a
mutation that was heterozygous in both parents.
In a boy with aldolase A deficiency, Kreuder et al. (1996) identified a
homozygous germline mutation in the ALDOA gene that resulted
substitution of a negatively charged glutamic acid with a positively
charged lysine at the highly conserved residue 206 (E206L; 103850.0002).
The affected residue is highly conserved within the subunit interface
region.
*FIELD* AV
.0001
GLYCOGEN STORAGE DISEASE XII
ALDOA, ASP128GLY
In a patient with red cell aldolase deficiency, or glycogen storage
disease XII (GSD12; 611881), Kishi et al. (1987) identified an A-G
transversion at nucleotide 386 in the codon for the 128th amino acid,
leading to a change from aspartic acid (GAU) to glycine (GGU) (D128G) in
the aldolase protein. The patient's enzyme from red cells and from
cultured lymphoblastoid cells was highly thermolabile, and the enzyme
expressed in E. coli was likewise thermolabile. Since asp128 is
conserved in aldolase A, B (612724), and C (103870) of eukaryotes,
including Drosophila, this residue likely has a crucial role in
maintaining the correct spatial structure or in performing the catalytic
function of the enzyme. The parents had intermediate levels of red cell
aldolase A. The change in the aspartic acid codon extinguished an Fok1
restriction site (GGATG to GGGTG). Southern blot analysis of genomic DNA
showed that the patient was homozygous for a mutation that was
heterozygous in both parents.
.0002
GLYCOGEN STORAGE DISEASE XII
ALDOA, GLU206LYS
Kreuder et al. (1996) described a 4 1/2-year-old boy with predominantly
myopathic symptoms of aldolase A deficiency (611881) due to substitution
of a single amino acid within the subunit interface most essential for
the tetrameric structure of the enzyme. The patient showed muscle
weakness and premature muscle fatigue. He was unable to walk for more
than 10 minutes or climb more than 20 steps at a time. Several
unexplained episodes of jaundice and anemia required blood transfusions
during the first year of life. The parents were healthy and
nonconsanguineous. The patient showed slight jaundice, diminished muscle
mass, reduced muscle tone, and proximal muscle weakness. The liver and
spleen were somewhat enlarged. Creatine kinase was markedly elevated in
the blood of this patient, and several muscle enzymes, as well as serum
bilirubin, were increased. Codon 206 of the ALDOA gene was found to have
a homozygous transition from GAG (glu) to AAG (lys) (E206K). The authors
noted that a glutamate is present in all human aldolases at position 206
of the enzyme. Both parents and a healthy brother were heterozygous for
the mutation.
*FIELD* SA
Penhoet et al. (1966); Tolan et al. (1987)
*FIELD* RF
1. Amberger, J. S.: Personal Communication. Baltimore, Md. 3/6/2008.
2. Charlesworth, D.: Starch-gel electrophoresis of four enzymes from
human red blood cells: glyceraldehyde-3-phosphate dehydrogenase, fructoaldolase,
glyoxalase II and sorbitol dehydrogenase. Ann. Hum. Genet. 35: 477-484,
1972.
3. Cohen-Haguenauer, O.; Van Cong, N.; Mennecier, F.; Kahn, A.; Frezal,
J.: The human aldolase A gene is on chromosome 16.(Abstract) Cytogenet.
Cell Genet. 40: 605, 1985.
4. Comings, D. E.: Evidence of ancient tetraploidy and conservation
of linkage groups in mammalian chromosomes. Nature 238: 455-457,
1972.
5. Freemont, P. S.; Dunbar, B.; Fothergill-Gilmore, L. A.: The complete
amino acid sequence of human skeletal-muscle fructose-bisphosphate
aldolase. Biochem. J. 249: 779-788, 1988.
6. Harris, H.: Personal Communication. London, England 1974.
7. Izzo, P.; Costanzo, P.; Lupo, A.; Rippa, E.; Paolella, G.; Salvatore,
F.: Human aldolase A gene: structural organization and tissue-specific
expression by multiple promoters and alternate mRNA processing. Europ.
J. Biochem. 174: 569-578, 1988.
8. Kishi, H.; Mukai, T.; Hirono, A.; Fujii, H.; Miwa, S.; Hori, K.
: Human aldolase A deficiency associated with a hemolytic anemia:
thermolabile aldolase due to a single base mutation. Proc. Nat. Acad.
Sci. 84: 8623-8627, 1987.
9. Kreuder, J.; Borkhardt, A.; Repp, R.; Pekrun, A.; Gottsche, B.;
Gottschalk, U.; Reichmann, H.; Schachenmayr, W.; Schlegel, K.; Lampert,
F.: Brief report: inherited metabolic myopathy and hemolysis due
to a mutation in aldolase A. New Eng. J. Med. 334: 1100-1104, 1996.
10. Kukita, A.; Yoshida, M. C.; Fukushige, S.; Sakakibara, M.; Joh,
K.; Mukai, T.; Hori, K.: Molecular gene mapping of human aldolase
A (ALDOA) gene to chromosome 16. Hum. Genet. 76: 20-26, 1987.
11. Kukita, A.; Yoshida, M. C.; Sakakibara, M.; Mukai, T.; Hori, K.
: Molecular gene mapping of the structural gene for human aldolase
A (ALDOA) to chromosome 22.(Abstract) Cytogenet. Cell Genet. 40:
674, 1985.
12. Ohno, S.: Ancient linkage groups and frozen accidents. Nature 244:
259-262, 1973.
13. Penhoet, E.; Rajkumar, T.; Rutter, W. J.: Multiple forms of fructose
diphosphate aldolase in mammalian tissues. Proc. Nat. Acad. Sci. 56:
1275-1282, 1966.
14. Rottmann, W. H.; Tolan, D. R.; Penhoet, E. E.: Complete amino
acid sequence for human aldolase B derived from cDNA and genomic clones. Proc.
Nat. Acad. Sci. 81: 2738-2742, 1984.
15. Sakakibara, M.; Mukai, T.; Hori, K.: Nucleotide sequence of a
cDNA clone for human aldolase: a messenger RNA in the liver. Biochem.
Biophys. Res. Commun. 131: 413-420, 1985.
16. Serero, S.; Maire, P.; Van Cong, N.; Cohen-Haguenauer, O.; Gross,
M. S.; Jegou-Foubert, C.; de Tand, M. F.; Kahn, A.; Frezal, J.: Localization
of the active gene of aldolase on chromosome 16, and two aldolase
A pseudogenes on chromosomes 3 and 10. Hum. Genet. 78: 167-174,
1988.
17. Tolan, D. R.; Niclas, J.; Bruce, B. D.; Lebo, R. V.: Evolutionary
implications of the human aldolase-A, -B, -C, and -pseudogene chromosome
locations. Am. J. Hum. Genet. 41: 907-924, 1987.
*FIELD* CN
Joanna S. Amberger - updated: 3/6/2008
Victor A. McKusick - updated: 6/19/1997
Moyra Smith - updated: 6/3/1996
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
carol: 07/31/2009
ckniffin: 7/28/2009
carol: 4/14/2009
mgross: 3/6/2008
joanna: 3/6/2008
mgross: 3/17/2004
dkim: 7/17/1998
terry: 6/18/1998
alopez: 7/10/1997
jenny: 6/23/1997
mark: 6/19/1997
mark: 6/4/1996
carol: 6/3/1996
davew: 6/8/1994
warfield: 4/7/1994
carol: 4/6/1994
mimadm: 3/11/1994
supermim: 3/16/1992
carol: 1/27/1992
*RECORD*
*FIELD* NO
103850
*FIELD* TI
*103850 ALDOLASE A, FRUCTOSE-BISPHOSPHATE; ALDOA
;;FRUCTOSE-1,6-BISPHOSPHATE ALDOLASE A;;
read moreALDOLASE A; ALDA;;
ALDOLASE 1;;
FRUCTOALDOLASE A
*FIELD* TX
DESCRIPTION
Fructose-1,6-bisphosphate aldolase (EC 4.1.2.13) is a glycolytic enzyme
that catalyzes the reversible conversion of fructose-1,6-bisphosphate to
glyceraldehyde 3-phosphate and dihydroxyacetone phosphate. The enzyme is
a tetramer of identical 40-kD subunits. Vertebrates have 3 aldolase
isozymes, aldolases A, B (ALDOB; 612724), and C (ALDOC; 103870), which
are distinguished by their electrophoretic and catalytic properties. The
sequence of the aldolases around the active-site lysine is highly
conserved in evolution. Mammalian tissues express aldolase isozymes in a
well-characterized pattern. Developing embryo produces aldolase A, which
continues to be expressed in many adult tissues, sometimes at much
higher levels than in embryo. In adult muscle, aldolase A can be as much
as 5% of total cellular protein. In adult liver, kidney, and intestine,
aldolase A expression is repressed and aldolase B is produced. In brain
and other nervous tissue, aldolase A and C are expressed about equally.
In transformed liver cells, aldolase A replaces aldolase B (Rottmann et
al., 1984).
CLONING
Electrophoretic variants of fructoaldolase were reported by Charlesworth
(1972).
Sakakibara et al. (1985) cloned aldolase A from a human liver cDNA
library. The deduced protein contains 363 amino acids. RNA blot analysis
revealed a 1.6-kb ALDOA mRNA in skeletal muscle and a 1.7-kb ALDOA mRNA
in liver and placenta.
Freemont et al. (1988) presented the complete amino acid sequence of
human skeletal muscle fructose-bisphosphate aldolase, comprising 363
residues.
GENE STRUCTURE
Izzo et al. (1988) found that the ALDOA gene spans 7.5 kb and contains
12 exons. It occurs as a single copy per haploid human genome. Eight
exons containing the coding sequence were common to all mRNAs extracted
from several mammalian sources. Four additional exons were identified in
the 5-prime UTR: the first was contained in the ubiquitous mRNA, the
second in the muscle-specific mRNA, and the third and fourth in a minor
mRNA in human liver. S(1)-nuclease-protection analysis of the 5-prime
end of mRNA from cultured fibroblasts, muscle, and hepatoma cell lines
revealed 4 different transcription initiation sites. The presence of
conventional sequences for 4 eukaryotic promoters was also demonstrated.
The nucleotide similarities in the coding region and the intron-exon
organization of aldolases A, B, and C confirmed that they arose from a
common ancestral gene, with aldolase B diverging first.
MAPPING
Harris (1974) concluded that 3 loci determine aldolase. Cohen-Haguenauer
et al. (1985) assigned aldolase A to chromosome 16, whereas Kukita et
al. (1985) assigned it to chromosome 22. However, Kukita et al. (1987)
mapped the ALDOA gene to chromosome 16 by 3 different methods: molecular
hybridization to hybrid cell DNA, molecular hybridization to DNA of
sorted metaphase chromosomes, and in situ hybridization. In situ
hybridization indicated that the gene is located on the chromosome
16q22-q24 band. Serero et al. (1988) also assigned the aldolase A gene
to chromosome 16 by Southern blot analysis of human genomic DNA with a
cDNA probe. Aldolase A pseudogenes were found on chromosomes 3 and 10.
The map location of the 3 aldolase genes and the aldolase pseudogene
(see 612724) is of considerable interest from the point of view of
chromosome evolution. The 4 genes are found on 2 pairs of
morphologically similar chromosomes, 9 and 10, and 16 and 17. These
homeologous (i.e., of similar origin) chromosome pairs may have arisen
from 1 or 2 tetraploidization events (Comings, 1972; Ohno, 1973). As
predicted by the chromosomal locations, the coding sequences of the
expressed aldolase A and C genes on chromosomes 16 and 17, respectively,
are more homologous to each other than either of them is to the
expressed aldolase B gene on chromosome 9.
Amberger (2008) mapped the ALDOA gene to chromosome 16p11.2 based on an
alignment of the ALDOA sequence (GenBank GENBANK M11560) with the
genomic sequence (build 36.2).
MOLECULAR GENETICS
Kishi et al. (1987) studied a patient with red cell aldolase deficiency,
or glycogen storage disease XII (GSD12; 611881), and identified a
mutation in the ALDOA gene that resulted in an asp128-to-gly (D128G;
103850.0001) substitution in the protein. The patient's enzyme from red
cells and from cultured lymphoblastoid cells was highly thermolabile,
and the enzyme expressed in E. coli was likewise thermolabile. The
parents had intermediate levels of red cell aldolase A. Southern blot
analysis of genomic DNA showed that the patient was homozygous for a
mutation that was heterozygous in both parents.
In a boy with aldolase A deficiency, Kreuder et al. (1996) identified a
homozygous germline mutation in the ALDOA gene that resulted
substitution of a negatively charged glutamic acid with a positively
charged lysine at the highly conserved residue 206 (E206L; 103850.0002).
The affected residue is highly conserved within the subunit interface
region.
*FIELD* AV
.0001
GLYCOGEN STORAGE DISEASE XII
ALDOA, ASP128GLY
In a patient with red cell aldolase deficiency, or glycogen storage
disease XII (GSD12; 611881), Kishi et al. (1987) identified an A-G
transversion at nucleotide 386 in the codon for the 128th amino acid,
leading to a change from aspartic acid (GAU) to glycine (GGU) (D128G) in
the aldolase protein. The patient's enzyme from red cells and from
cultured lymphoblastoid cells was highly thermolabile, and the enzyme
expressed in E. coli was likewise thermolabile. Since asp128 is
conserved in aldolase A, B (612724), and C (103870) of eukaryotes,
including Drosophila, this residue likely has a crucial role in
maintaining the correct spatial structure or in performing the catalytic
function of the enzyme. The parents had intermediate levels of red cell
aldolase A. The change in the aspartic acid codon extinguished an Fok1
restriction site (GGATG to GGGTG). Southern blot analysis of genomic DNA
showed that the patient was homozygous for a mutation that was
heterozygous in both parents.
.0002
GLYCOGEN STORAGE DISEASE XII
ALDOA, GLU206LYS
Kreuder et al. (1996) described a 4 1/2-year-old boy with predominantly
myopathic symptoms of aldolase A deficiency (611881) due to substitution
of a single amino acid within the subunit interface most essential for
the tetrameric structure of the enzyme. The patient showed muscle
weakness and premature muscle fatigue. He was unable to walk for more
than 10 minutes or climb more than 20 steps at a time. Several
unexplained episodes of jaundice and anemia required blood transfusions
during the first year of life. The parents were healthy and
nonconsanguineous. The patient showed slight jaundice, diminished muscle
mass, reduced muscle tone, and proximal muscle weakness. The liver and
spleen were somewhat enlarged. Creatine kinase was markedly elevated in
the blood of this patient, and several muscle enzymes, as well as serum
bilirubin, were increased. Codon 206 of the ALDOA gene was found to have
a homozygous transition from GAG (glu) to AAG (lys) (E206K). The authors
noted that a glutamate is present in all human aldolases at position 206
of the enzyme. Both parents and a healthy brother were heterozygous for
the mutation.
*FIELD* SA
Penhoet et al. (1966); Tolan et al. (1987)
*FIELD* RF
1. Amberger, J. S.: Personal Communication. Baltimore, Md. 3/6/2008.
2. Charlesworth, D.: Starch-gel electrophoresis of four enzymes from
human red blood cells: glyceraldehyde-3-phosphate dehydrogenase, fructoaldolase,
glyoxalase II and sorbitol dehydrogenase. Ann. Hum. Genet. 35: 477-484,
1972.
3. Cohen-Haguenauer, O.; Van Cong, N.; Mennecier, F.; Kahn, A.; Frezal,
J.: The human aldolase A gene is on chromosome 16.(Abstract) Cytogenet.
Cell Genet. 40: 605, 1985.
4. Comings, D. E.: Evidence of ancient tetraploidy and conservation
of linkage groups in mammalian chromosomes. Nature 238: 455-457,
1972.
5. Freemont, P. S.; Dunbar, B.; Fothergill-Gilmore, L. A.: The complete
amino acid sequence of human skeletal-muscle fructose-bisphosphate
aldolase. Biochem. J. 249: 779-788, 1988.
6. Harris, H.: Personal Communication. London, England 1974.
7. Izzo, P.; Costanzo, P.; Lupo, A.; Rippa, E.; Paolella, G.; Salvatore,
F.: Human aldolase A gene: structural organization and tissue-specific
expression by multiple promoters and alternate mRNA processing. Europ.
J. Biochem. 174: 569-578, 1988.
8. Kishi, H.; Mukai, T.; Hirono, A.; Fujii, H.; Miwa, S.; Hori, K.
: Human aldolase A deficiency associated with a hemolytic anemia:
thermolabile aldolase due to a single base mutation. Proc. Nat. Acad.
Sci. 84: 8623-8627, 1987.
9. Kreuder, J.; Borkhardt, A.; Repp, R.; Pekrun, A.; Gottsche, B.;
Gottschalk, U.; Reichmann, H.; Schachenmayr, W.; Schlegel, K.; Lampert,
F.: Brief report: inherited metabolic myopathy and hemolysis due
to a mutation in aldolase A. New Eng. J. Med. 334: 1100-1104, 1996.
10. Kukita, A.; Yoshida, M. C.; Fukushige, S.; Sakakibara, M.; Joh,
K.; Mukai, T.; Hori, K.: Molecular gene mapping of human aldolase
A (ALDOA) gene to chromosome 16. Hum. Genet. 76: 20-26, 1987.
11. Kukita, A.; Yoshida, M. C.; Sakakibara, M.; Mukai, T.; Hori, K.
: Molecular gene mapping of the structural gene for human aldolase
A (ALDOA) to chromosome 22.(Abstract) Cytogenet. Cell Genet. 40:
674, 1985.
12. Ohno, S.: Ancient linkage groups and frozen accidents. Nature 244:
259-262, 1973.
13. Penhoet, E.; Rajkumar, T.; Rutter, W. J.: Multiple forms of fructose
diphosphate aldolase in mammalian tissues. Proc. Nat. Acad. Sci. 56:
1275-1282, 1966.
14. Rottmann, W. H.; Tolan, D. R.; Penhoet, E. E.: Complete amino
acid sequence for human aldolase B derived from cDNA and genomic clones. Proc.
Nat. Acad. Sci. 81: 2738-2742, 1984.
15. Sakakibara, M.; Mukai, T.; Hori, K.: Nucleotide sequence of a
cDNA clone for human aldolase: a messenger RNA in the liver. Biochem.
Biophys. Res. Commun. 131: 413-420, 1985.
16. Serero, S.; Maire, P.; Van Cong, N.; Cohen-Haguenauer, O.; Gross,
M. S.; Jegou-Foubert, C.; de Tand, M. F.; Kahn, A.; Frezal, J.: Localization
of the active gene of aldolase on chromosome 16, and two aldolase
A pseudogenes on chromosomes 3 and 10. Hum. Genet. 78: 167-174,
1988.
17. Tolan, D. R.; Niclas, J.; Bruce, B. D.; Lebo, R. V.: Evolutionary
implications of the human aldolase-A, -B, -C, and -pseudogene chromosome
locations. Am. J. Hum. Genet. 41: 907-924, 1987.
*FIELD* CN
Joanna S. Amberger - updated: 3/6/2008
Victor A. McKusick - updated: 6/19/1997
Moyra Smith - updated: 6/3/1996
*FIELD* CD
Victor A. McKusick: 6/4/1986
*FIELD* ED
carol: 07/31/2009
ckniffin: 7/28/2009
carol: 4/14/2009
mgross: 3/6/2008
joanna: 3/6/2008
mgross: 3/17/2004
dkim: 7/17/1998
terry: 6/18/1998
alopez: 7/10/1997
jenny: 6/23/1997
mark: 6/19/1997
mark: 6/4/1996
carol: 6/3/1996
davew: 6/8/1994
warfield: 4/7/1994
carol: 4/6/1994
mimadm: 3/11/1994
supermim: 3/16/1992
carol: 1/27/1992
MIM
611881
*RECORD*
*FIELD* NO
611881
*FIELD* TI
#611881 GLYCOGEN STORAGE DISEASE XII; GSD12
;;GSD XII;;
ALDOLASE A DEFICIENCY;;
ALDOA DEFICIENCY;;
read moreALDOLASE DEFICIENCY, RED CELL;;
RED CELL ALDOLASE DEFICIENCY
*FIELD* TX
A number sign (#) is used with this entry because aldolase A deficiency,
also known as glycogen storage disease XII (GSD12), is caused by
homozygous mutation in the ALDOA gene (103850).
DESCRIPTION
Aldolase A deficiency is an autosomal recessive disorder associated with
hereditary hemolytic anemia (Kishi et al., 1987).
CLINICAL FEATURES
Beutler et al. (1973) described a son of first-cousin parents who had
nonspherocytic hemolytic anemia, mental retardation, and increased
hepatic glycogen due, apparently, to deficiency of red cell aldolase.
Puzzlingly, both parents had normal levels of red cell aldolase. The
patient was presented again at the Birth Defects Conference in Vancouver
in 1976 (Lowry and Hanson, 1977). He showed many dysmorphic features,
some of which (ptosis, epicanthi, short neck, and low posterior
hairline) were reminiscent of Noonan syndrome (163950). The patient
reported by Beutler et al. (1973) had an unstable enzyme that became
depleted in enucleated erythrocytes. Consequently, energy production was
impaired and membrane stability decreased with declining ion transport
activity. Hurst et al. (1987) described a brother and sister with mental
retardation, short stature, delayed puberty, hemolytic anemia, and
abnormal facial appearance. The similarities to the boy reported by
Beutler et al. (1973) were striking.
Miwa et al. (1981) reported 2 patients with red cell aldolase deficiency
associated with congenital nonspherocytic hemolytic anemia. The proband
was a 14-month-old Japanese boy whose parents were probably
consanguineous. He had mild to moderate anemia that was aggravated by
upper respiratory infections, 1 cm hepatomegaly, and 2.5 cm
splenomegaly, but showed no growth or mental retardation and did not
have dysmorphic features. Red cell aldolase activity was 6% of the
normal mean. The enzyme was unstable with respect to heat, and Km for
fructose 1,6-diphosphate was high. The parents and other heterozygotes
showed intermediate enzyme activity between that of the proband and that
of normal subjects. The other affected patient reported by Miwa et al.
(1981) was the 13-year-old nephew of the proband's maternal grandmother,
and he presented with a phenotype similar to that of the proband.
Kreuder et al. (1996) described a boy with aldolase deficiency who
presented with predominantly myopathic symptoms, including muscle
weakness and premature muscle fatigue. He had episodes of anemia and
jaundice and was prone to episodes of rhabdomyolysis during febrile
illness. Biochemical assays revealed a profound reduction in muscle and
red cell aldolase levels and a decrease in thermostability of residual
enzyme.
MAPPING
Aldolase A deficiency is caused by mutation in the ALDOA gene, which
maps to chromosome 16p11.2 (Amberger, 2008).
MOLECULAR GENETICS
Kishi et al. (1987) studied a patient with red cell aldolase deficiency
reported by Miwa et al. (1981) and identified a mutation in the ALDOA
gene that resulted in an asp128-to-gly (D128G; 103850.0001) substitution
in the protein. The patient's enzyme from red cells and from cultured
lymphoblastoid cells was highly thermolabile, and the enzyme expressed
in E. coli was likewise thermolabile. The parents had intermediate
levels of red cell aldolase A. Southern blot analysis of genomic DNA
showed that the patient was homozygous for a mutation that was
heterozygous in both parents.
In a boy they reported with aldolase A deficiency, Kreuder et al. (1996)
identified a homozygous germline mutation in the ALDOA gene that
resulted substitution of a negatively charged glutamic acid with a
positively charged lysine at the highly conserved residue 206 (E206L;
103850.0002).
*FIELD* RF
1. Amberger, J. S.: Personal Communication. Baltimore, Md. 3/6/2008.
2. Beutler, E.; Scott, S.; Bishop, A.; Margolis, N.; Matsumoto, F.;
Kuhl, W.: Red cell aldolase deficiency and hemolytic anemia: a new
syndrome. Trans. Assoc. Am. Phys. 86: 154-166, 1973.
3. Hurst, J. A.; Baraitser, M.; Winter, R. M.: A syndrome of mental
retardation, short stature, hemolytic anemia, delayed puberty, and
abnormal facial appearance: similarities to a report of aldolase A
deficiency. Am. J. Med. Genet. 28: 965-970, 1987.
4. Kishi, H.; Mukai, T.; Hirono, A.; Fujii, H.; Miwa, S.; Hori, K.
: Human aldolase A deficiency associated with a hemolytic anemia:
thermolabile aldolase due to a single base mutation. Proc. Nat. Acad.
Sci. 84: 8623-8627, 1987.
5. Kreuder, J.; Borkhardt, A.; Repp, R.; Pekrun, A.; Gottsche, B.;
Gottschalk, U.; Reichmann, H.; Schachenmayr, W.; Schlegel, K.; Lampert,
F.: Brief report: inherited metabolic myopathy and hemolysis due
to a mutation in aldolase A. New Eng. J. Med. 334: 1100-1104, 1996.
6. Lowry, R. B.; Hanson, J. W.: Aldolase A deficiency with syndrome
of growth and developmental retardation, midfacial hypoplasia, hepatomegaly,
and consanguineous parents. Birth Defects Orig. Art. Ser. XIII(3B):
222-228, 1977.
7. Miwa, S.; Fujii, H.; Tani, K.; Takahashi, K.; Takegawa, S.; Fujinami,
N.; Sakurai, M.; Kubo, M.; Tanimoto, Y.; Kato, T.; Matsumoto, N.:
Two cases of red cell aldolase deficiency associated with hereditary
hemolytic anemia in a Japanese family. Am. J. Hemat. 11: 425-437,
1981.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Height];
Short stature
HEAD AND NECK:
[Eyes];
Ptosis;
Epicanthus;
[Neck];
Short neck;
Low posterior hairline
ABDOMEN:
[Liver];
Jaundice;
[Biliary tract];
Cholelithiasis;
Cholecystitis;
[Spleen];
Splenomegaly
SKIN, NAILS, HAIR:
[Skin];
Jaundice
MUSCLE, SOFT TISSUE:
Myopathy (in some patients)
NEUROLOGIC:
[Central nervous system];
Mental retardation (in some patients)
ENDOCRINE FEATURES:
Delayed puberty
HEMATOLOGY:
Congenital nonspherocytic hemolytic anemia;
Normocytic anemia;
Normochromic anemia;
Normal red cell osmotic fragility
LABORATORY ABNORMALITIES:
Aldolase A deficiency
MOLECULAR BASIS:
Caused by mutation in the Aldolase A, fructose-bisphosphatase gene
(ALDOA, 103850.0001)
*FIELD* CD
Joanna S. Amberger: 3/8/2012
*FIELD* ED
joanna: 05/15/2012
joanna: 3/8/2012
*FIELD* CN
Matthew B. Gross - updated: 3/6/2008
*FIELD* CD
Victor A. McKusick: 3/6/2008
*FIELD* ED
joanna: 03/08/2012
carol: 7/30/2009
ckniffin: 7/28/2009
mgross: 3/6/2008
*RECORD*
*FIELD* NO
611881
*FIELD* TI
#611881 GLYCOGEN STORAGE DISEASE XII; GSD12
;;GSD XII;;
ALDOLASE A DEFICIENCY;;
ALDOA DEFICIENCY;;
read moreALDOLASE DEFICIENCY, RED CELL;;
RED CELL ALDOLASE DEFICIENCY
*FIELD* TX
A number sign (#) is used with this entry because aldolase A deficiency,
also known as glycogen storage disease XII (GSD12), is caused by
homozygous mutation in the ALDOA gene (103850).
DESCRIPTION
Aldolase A deficiency is an autosomal recessive disorder associated with
hereditary hemolytic anemia (Kishi et al., 1987).
CLINICAL FEATURES
Beutler et al. (1973) described a son of first-cousin parents who had
nonspherocytic hemolytic anemia, mental retardation, and increased
hepatic glycogen due, apparently, to deficiency of red cell aldolase.
Puzzlingly, both parents had normal levels of red cell aldolase. The
patient was presented again at the Birth Defects Conference in Vancouver
in 1976 (Lowry and Hanson, 1977). He showed many dysmorphic features,
some of which (ptosis, epicanthi, short neck, and low posterior
hairline) were reminiscent of Noonan syndrome (163950). The patient
reported by Beutler et al. (1973) had an unstable enzyme that became
depleted in enucleated erythrocytes. Consequently, energy production was
impaired and membrane stability decreased with declining ion transport
activity. Hurst et al. (1987) described a brother and sister with mental
retardation, short stature, delayed puberty, hemolytic anemia, and
abnormal facial appearance. The similarities to the boy reported by
Beutler et al. (1973) were striking.
Miwa et al. (1981) reported 2 patients with red cell aldolase deficiency
associated with congenital nonspherocytic hemolytic anemia. The proband
was a 14-month-old Japanese boy whose parents were probably
consanguineous. He had mild to moderate anemia that was aggravated by
upper respiratory infections, 1 cm hepatomegaly, and 2.5 cm
splenomegaly, but showed no growth or mental retardation and did not
have dysmorphic features. Red cell aldolase activity was 6% of the
normal mean. The enzyme was unstable with respect to heat, and Km for
fructose 1,6-diphosphate was high. The parents and other heterozygotes
showed intermediate enzyme activity between that of the proband and that
of normal subjects. The other affected patient reported by Miwa et al.
(1981) was the 13-year-old nephew of the proband's maternal grandmother,
and he presented with a phenotype similar to that of the proband.
Kreuder et al. (1996) described a boy with aldolase deficiency who
presented with predominantly myopathic symptoms, including muscle
weakness and premature muscle fatigue. He had episodes of anemia and
jaundice and was prone to episodes of rhabdomyolysis during febrile
illness. Biochemical assays revealed a profound reduction in muscle and
red cell aldolase levels and a decrease in thermostability of residual
enzyme.
MAPPING
Aldolase A deficiency is caused by mutation in the ALDOA gene, which
maps to chromosome 16p11.2 (Amberger, 2008).
MOLECULAR GENETICS
Kishi et al. (1987) studied a patient with red cell aldolase deficiency
reported by Miwa et al. (1981) and identified a mutation in the ALDOA
gene that resulted in an asp128-to-gly (D128G; 103850.0001) substitution
in the protein. The patient's enzyme from red cells and from cultured
lymphoblastoid cells was highly thermolabile, and the enzyme expressed
in E. coli was likewise thermolabile. The parents had intermediate
levels of red cell aldolase A. Southern blot analysis of genomic DNA
showed that the patient was homozygous for a mutation that was
heterozygous in both parents.
In a boy they reported with aldolase A deficiency, Kreuder et al. (1996)
identified a homozygous germline mutation in the ALDOA gene that
resulted substitution of a negatively charged glutamic acid with a
positively charged lysine at the highly conserved residue 206 (E206L;
103850.0002).
*FIELD* RF
1. Amberger, J. S.: Personal Communication. Baltimore, Md. 3/6/2008.
2. Beutler, E.; Scott, S.; Bishop, A.; Margolis, N.; Matsumoto, F.;
Kuhl, W.: Red cell aldolase deficiency and hemolytic anemia: a new
syndrome. Trans. Assoc. Am. Phys. 86: 154-166, 1973.
3. Hurst, J. A.; Baraitser, M.; Winter, R. M.: A syndrome of mental
retardation, short stature, hemolytic anemia, delayed puberty, and
abnormal facial appearance: similarities to a report of aldolase A
deficiency. Am. J. Med. Genet. 28: 965-970, 1987.
4. Kishi, H.; Mukai, T.; Hirono, A.; Fujii, H.; Miwa, S.; Hori, K.
: Human aldolase A deficiency associated with a hemolytic anemia:
thermolabile aldolase due to a single base mutation. Proc. Nat. Acad.
Sci. 84: 8623-8627, 1987.
5. Kreuder, J.; Borkhardt, A.; Repp, R.; Pekrun, A.; Gottsche, B.;
Gottschalk, U.; Reichmann, H.; Schachenmayr, W.; Schlegel, K.; Lampert,
F.: Brief report: inherited metabolic myopathy and hemolysis due
to a mutation in aldolase A. New Eng. J. Med. 334: 1100-1104, 1996.
6. Lowry, R. B.; Hanson, J. W.: Aldolase A deficiency with syndrome
of growth and developmental retardation, midfacial hypoplasia, hepatomegaly,
and consanguineous parents. Birth Defects Orig. Art. Ser. XIII(3B):
222-228, 1977.
7. Miwa, S.; Fujii, H.; Tani, K.; Takahashi, K.; Takegawa, S.; Fujinami,
N.; Sakurai, M.; Kubo, M.; Tanimoto, Y.; Kato, T.; Matsumoto, N.:
Two cases of red cell aldolase deficiency associated with hereditary
hemolytic anemia in a Japanese family. Am. J. Hemat. 11: 425-437,
1981.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Height];
Short stature
HEAD AND NECK:
[Eyes];
Ptosis;
Epicanthus;
[Neck];
Short neck;
Low posterior hairline
ABDOMEN:
[Liver];
Jaundice;
[Biliary tract];
Cholelithiasis;
Cholecystitis;
[Spleen];
Splenomegaly
SKIN, NAILS, HAIR:
[Skin];
Jaundice
MUSCLE, SOFT TISSUE:
Myopathy (in some patients)
NEUROLOGIC:
[Central nervous system];
Mental retardation (in some patients)
ENDOCRINE FEATURES:
Delayed puberty
HEMATOLOGY:
Congenital nonspherocytic hemolytic anemia;
Normocytic anemia;
Normochromic anemia;
Normal red cell osmotic fragility
LABORATORY ABNORMALITIES:
Aldolase A deficiency
MOLECULAR BASIS:
Caused by mutation in the Aldolase A, fructose-bisphosphatase gene
(ALDOA, 103850.0001)
*FIELD* CD
Joanna S. Amberger: 3/8/2012
*FIELD* ED
joanna: 05/15/2012
joanna: 3/8/2012
*FIELD* CN
Matthew B. Gross - updated: 3/6/2008
*FIELD* CD
Victor A. McKusick: 3/6/2008
*FIELD* ED
joanna: 03/08/2012
carol: 7/30/2009
ckniffin: 7/28/2009
mgross: 3/6/2008