Full text data of BPGM
BPGM
[Confidence: medium (present in either hRBCD or BSc_CH or PM22954596)]
Bisphosphoglycerate mutase; BPGM; 5.4.2.4 (2,3-bisphosphoglycerate mutase, erythrocyte; 2,3-bisphosphoglycerate synthase; 3.1.3.13; 5.4.2.11; 2,3-diphosphoglycerate mutase; DPGM; BPG-dependent PGAM)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Bisphosphoglycerate mutase; BPGM; 5.4.2.4 (2,3-bisphosphoglycerate mutase, erythrocyte; 2,3-bisphosphoglycerate synthase; 3.1.3.13; 5.4.2.11; 2,3-diphosphoglycerate mutase; DPGM; BPG-dependent PGAM)
Note: presumably soluble (membrane word is not in UniProt keywords or features)
hRBCD
IPI00215979
IPI00215979 2,3-bisphosphoglycerate mutase Plays a major role in regulating hemoglobin oxygen affinity as a consequence of controlling 2,3-BPG concentration. Can also catalyze the reaction of EC 5.4.2.1 (mutase) and EC 3.1.3.13 (phosphatase), but with a reduced activity soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
IPI00215979 2,3-bisphosphoglycerate mutase Plays a major role in regulating hemoglobin oxygen affinity as a consequence of controlling 2,3-BPG concentration. Can also catalyze the reaction of EC 5.4.2.1 (mutase) and EC 3.1.3.13 (phosphatase), but with a reduced activity soluble n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a n/a cytoplasmic n/a found at its expected molecular weight found at molecular weight
UniProt
P07738
ID PMGE_HUMAN Reviewed; 259 AA.
AC P07738; A4D1N9;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 147.
DE RecName: Full=Bisphosphoglycerate mutase;
DE Short=BPGM;
DE EC=5.4.2.4;
DE AltName: Full=2,3-bisphosphoglycerate mutase, erythrocyte;
DE AltName: Full=2,3-bisphosphoglycerate synthase;
DE EC=3.1.3.13;
DE EC=5.4.2.11;
DE AltName: Full=2,3-diphosphoglycerate mutase;
DE Short=DPGM;
DE AltName: Full=BPG-dependent PGAM;
GN Name=BPGM;
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 PARTIAL PROTEIN SEQUENCE, MASS SPECTROMETRY, IDENTIFICATION OF VARIANT
RP BPGMD CYS-90, AND CHARACTERIZATION OF VARIANT BPGMD CYS-90.
RX PubMed=2542247;
RA Rosa R., Blouquit Y., Calvin M.C., Prome D., Prome J.C., Rosa J.;
RT "Isolation, characterization, and structure of a mutant 89 ArgTO:
RT bisphosphoglycerate mutase. Implication of the active site in the
RT mutation.";
RL J. Biol. Chem. 264:7837-7843(1989).
RN [2]
RP PRELIMINARY PROTEIN SEQUENCE OF 2-259, CLEAVAGE OF INITIATOR
RP METHIONINE, AND TISSUE SPECIFICITY.
RX PubMed=6313356;
RA Haggarty N.W., Dunbar B., Fothergill L.A.;
RT "The complete amino acid sequence of human erythrocyte
RT diphosphoglycerate mutase.";
RL EMBO J. 2:1213-1220(1983).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=3023066;
RA Joulin V., Peduzzi J., Romeo P.-H., Rosa R., Valentin C., Dubart A.,
RA Lapeyre B., Blouquit Y., Garel M.-C., Goossens M., Rosa J.,
RA Cohen-Solal M.;
RT "Molecular cloning and sequencing of the human erythrocyte 2,3-
RT bisphosphoglycerate mutase cDNA: revised amino acid sequence.";
RL EMBO J. 5:2275-2283(1986).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3036106;
RA Cohen-Solal M., Joulin V., Romeo P.-H., Rosa R., Valentin C.,
RA Garel M.-C., Rosa J.;
RT "Molecular cloning of the human 2,3-bisphosphoglycerate mutase cDNA
RT and revised amino acid sequence.";
RL Biomed. Biochim. Acta 46:S126-S130(1987).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2844822;
RA Joulin V., Garel M.-C., le Boulch P., Valentin C., Rosa R., Rosa J.,
RA Cohen-Solal M.;
RT "Isolation and characterization of the human 2,3-bisphosphoglycerate
RT mutase gene.";
RL J. Biol. Chem. 263:15785-15790(1988).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S.,
RA Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z.,
RA Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C.,
RA Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J.,
RA Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F.,
RA Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F.,
RA Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H.,
RA Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G.,
RA Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P.,
RA Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J.,
RA Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F.,
RA Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B.,
RA Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W.,
RA Mural R.J., Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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].
RC TISSUE=Colon;
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 PROTEIN SEQUENCE OF 2-46; 144-168 AND 182-206, GLYCATION AT LYS-3;
RP LYS-5; LYS-18; LYS-43; LYS-159 AND LYS-197, AND LACK OF GLYCATION AT
RP LYS-29; LYS-46; LYS-143; LYS-181; LYS-246; LYS-247; LYS-253; LYS-258
RP AND LYS-259.
RX PubMed=9832630; DOI=10.1093/oxfordjournals.jbchem.a022243;
RA Fujita T., Suzuki K., Tada T., Yoshihara Y., Hamaoka R., Uchida K.,
RA Matuo Y., Sasaki T., Hanafusa T., Taniguchi N.;
RT "Human erythrocyte bisphosphoglycerate mutase: inactivation by
RT glycation in vivo and in vitro.";
RL J. Biochem. 124:1237-1244(1998).
RN [11]
RP PROTEIN SEQUENCE OF 104-114.
RX PubMed=8440681;
RA Stafforini D.M., Rollins E.N., Prescott S.M., McIntyre T.M.;
RT "The platelet-activating factor acetylhydrolase from human
RT erythrocytes. Purification and properties.";
RL J. Biol. Chem. 268:3857-3865(1993).
RN [12]
RP ENZYME REGULATION.
RX PubMed=10477269; DOI=10.1042/0264-6021:3420581;
RA Mulquiney P.J., Kuchel P.W.;
RT "Model of 2,3-bisphosphoglycerate metabolism in the human erythrocyte
RT based on detailed enzyme kinetic equations: equations and parameter
RT refinement.";
RL Biochem. J. 342:581-596(1999).
RN [13]
RP TISSUE SPECIFICITY.
RX PubMed=16246416; DOI=10.1016/j.placenta.2005.08.010;
RA Pritlove D.C., Gu M., Boyd C.A., Randeva H.S., Vatish M.;
RT "Novel placental expression of 2,3-bisphosphoglycerate mutase.";
RL Placenta 27:924-927(2006).
RN [14]
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 [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
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 [16]
RP 3D-STRUCTURE MODELING.
RX PubMed=1387804; DOI=10.1016/0300-9084(92)90149-9;
RA Craescu C.T., Schaad O., Garel M.-C., Rosa R., Edelstein S.J.;
RT "Structural modeling of the human erythrocyte bisphosphoglycerate
RT mutase.";
RL Biochimie 74:519-526(1992).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 1-258 IN COMPLEXES WITH
RP 3-PHOSPHO-D-GLYCERATE AND 2,3-BISPHOSPHO-D-GLYCERATE, SUBUNIT, AND
RP ACTIVE SITE.
RX PubMed=17052986; DOI=10.1074/jbc.M606421200;
RA Wang Y., Liu L., Wei Z., Cheng Z., Lin Y., Gong W.;
RT "Seeing the process of histidine phosphorylation in human
RT bisphosphoglycerate mutase.";
RL J. Biol. Chem. 281:39642-39648(2006).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS), AND ENZYME REGULATION.
RX PubMed=21045285; DOI=10.1107/S1744309110035475;
RA Patterson A., Price N.C., Nairn J.;
RT "Unliganded structure of human bisphosphoglycerate mutase reveals
RT side-chain movements induced by ligand binding.";
RL Acta Crystallogr. F 66:1415-1420(2010).
RN [19]
RP VARIANT BPGMD CYS-90.
RX PubMed=1421379;
RA Lemarchandel V., Joulin V., Valentin C., Rosa R., Galacteros F.,
RA Rosa J., Cohen-Solal M.;
RT "Compound heterozygosity in a complete erythrocyte bisphosphoglycerate
RT mutase deficiency.";
RL Blood 80:2643-2649(1992).
RN [20]
RP VARIANT BPGMD GLN-62.
RX PubMed=15054810; DOI=10.1002/ajh.20014;
RA Hoyer J.D., Allen S.L., Beutler E., Kubik K., West C., Fairbanks V.F.;
RT "Erythrocytosis due to bisphosphoglycerate mutase deficiency with
RT concurrent glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.";
RL Am. J. Hematol. 75:205-208(2004).
CC -!- FUNCTION: Plays a major role in regulating hemoglobin oxygen
CC affinity by controlling the levels of its allosteric effector 2,3-
CC bisphosphoglycerate (2,3-BPG). Also exhibits mutase (EC 5.4.2.1)
CC and phosphatase (EC 3.1.3.13) activities.
CC -!- CATALYTIC ACTIVITY: 3-phospho-D-glyceroyl phosphate = 2,3-
CC bisphospho-D-glycerate.
CC -!- CATALYTIC ACTIVITY: 2-phospho-D-glycerate = 3-phospho-D-glycerate.
CC -!- CATALYTIC ACTIVITY: 2,3-bisphospho-D-glycerate + H(2)O = 3-
CC phospho-D-glycerate + phosphate.
CC -!- ENZYME REGULATION: At alkaline pH BPGM favors the synthase
CC reaction; however, at lower pH the phosphatase reaction is
CC dominant. Inhibited by citrate.
CC -!- SUBUNIT: Homodimer.
CC -!- TISSUE SPECIFICITY: Expressed in red blood cells. Expressed in
CC non-erythroid cells of the placenta; present in the
CC syncytiotrophoblast layer of the placental villi at the feto-
CC maternal interface (at protein level).
CC -!- PTM: Glycation of Lys-159 in diabetic patients inactivates the
CC enzyme.
CC -!- DISEASE: Bisphosphoglycerate mutase deficiency (BPGMD)
CC [MIM:222800]: A disease characterized by hemolytic anemia,
CC splenomegaly, cholelithiasis and cholecystitis. Note=The disease
CC is caused by mutations affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the phosphoglycerate mutase family. BPG-
CC dependent PGAM subfamily.
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DR EMBL; X04327; CAA27858.1; -; mRNA.
DR EMBL; M23068; AAA51840.1; -; Genomic_DNA.
DR EMBL; M23067; AAA51840.1; JOINED; Genomic_DNA.
DR EMBL; AK315439; BAG37827.1; -; mRNA.
DR EMBL; CH236950; EAL24067.1; -; Genomic_DNA.
DR EMBL; CH471070; EAW83821.1; -; Genomic_DNA.
DR EMBL; BC017050; AAH17050.1; -; mRNA.
DR PIR; A31999; PMHUBM.
DR RefSeq; NP_001715.1; NM_001724.4.
DR RefSeq; NP_954655.1; NM_199186.2.
DR RefSeq; XP_005250602.1; XM_005250545.1.
DR UniGene; Hs.198365; -.
DR PDB; 1T8P; X-ray; 2.50 A; A/B=1-259.
DR PDB; 2A9J; X-ray; 2.00 A; A/B=1-259.
DR PDB; 2F90; X-ray; 2.00 A; A/B=1-259.
DR PDB; 2H4X; X-ray; 1.85 A; A/B=1-259.
DR PDB; 2H4Z; X-ray; 2.00 A; A/B=1-259.
DR PDB; 2H52; X-ray; 2.00 A; A/B=1-259.
DR PDB; 2HHJ; X-ray; 1.50 A; A/B=1-259.
DR PDB; 3NFY; X-ray; 1.94 A; A/B=1-259.
DR PDBsum; 1T8P; -.
DR PDBsum; 2A9J; -.
DR PDBsum; 2F90; -.
DR PDBsum; 2H4X; -.
DR PDBsum; 2H4Z; -.
DR PDBsum; 2H52; -.
DR PDBsum; 2HHJ; -.
DR PDBsum; 3NFY; -.
DR ProteinModelPortal; P07738; -.
DR SMR; P07738; 2-256.
DR IntAct; P07738; 8.
DR STRING; 9606.ENSP00000342032; -.
DR PhosphoSite; P07738; -.
DR DMDM; 130350; -.
DR REPRODUCTION-2DPAGE; IPI00215979; -.
DR PaxDb; P07738; -.
DR PeptideAtlas; P07738; -.
DR PRIDE; P07738; -.
DR DNASU; 669; -.
DR Ensembl; ENST00000344924; ENSP00000342032; ENSG00000172331.
DR Ensembl; ENST00000393132; ENSP00000376840; ENSG00000172331.
DR Ensembl; ENST00000418040; ENSP00000399838; ENSG00000172331.
DR GeneID; 669; -.
DR KEGG; hsa:669; -.
DR UCSC; uc003vrv.3; human.
DR CTD; 669; -.
DR GeneCards; GC07P134331; -.
DR HGNC; HGNC:1093; BPGM.
DR HPA; HPA016493; -.
DR HPA; HPA028735; -.
DR MIM; 222800; phenotype.
DR MIM; 613896; gene.
DR neXtProt; NX_P07738; -.
DR Orphanet; 714; Hemolytic anemia due to diphosphoglycerate mutase deficiency.
DR PharmGKB; PA25401; -.
DR eggNOG; COG0588; -.
DR HOGENOM; HOG000221682; -.
DR HOVERGEN; HBG027528; -.
DR InParanoid; P07738; -.
DR KO; K01837; -.
DR OMA; NLHAVGP; -.
DR OrthoDB; EOG7XM2ZV; -.
DR PhylomeDB; P07738; -.
DR BioCyc; MetaCyc:HS10491-MONOMER; -.
DR SABIO-RK; P07738; -.
DR ChiTaRS; BPGM; human.
DR EvolutionaryTrace; P07738; -.
DR GenomeRNAi; 669; -.
DR NextBio; 2738; -.
DR PRO; PR:P07738; -.
DR ArrayExpress; P07738; -.
DR Bgee; P07738; -.
DR CleanEx; HS_BPGM; -.
DR Genevestigator; P07738; -.
DR GO; GO:0004083; F:bisphosphoglycerate 2-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004082; F:bisphosphoglycerate mutase activity; TAS:ProtInc.
DR GO; GO:0004619; F:phosphoglycerate mutase activity; IEA:InterPro.
DR GO; GO:0005975; P:carbohydrate metabolic process; NAS:ProtInc.
DR GO; GO:0006096; P:glycolysis; IEA:UniProtKB-KW.
DR GO; GO:0007585; P:respiratory gaseous exchange; TAS:ProtInc.
DR InterPro; IPR013078; His_Pase_superF_clade-1.
DR InterPro; IPR001345; PG/BPGM_mutase_AS.
DR InterPro; IPR005952; Phosphogly_mut1.
DR PANTHER; PTHR11931; PTHR11931; 1.
DR Pfam; PF00300; His_Phos_1; 1.
DR SMART; SM00855; PGAM; 1.
DR TIGRFAMs; TIGR01258; pgm_1; 1.
DR PROSITE; PS00175; PG_MUTASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome;
KW Direct protein sequencing; Disease mutation; Glycation; Glycolysis;
KW Glycoprotein; Hereditary hemolytic anemia; Hydrolase; Isomerase;
KW Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 259 Bisphosphoglycerate mutase.
FT /FTId=PRO_0000179834.
FT REGION 23 24 2,3-bisphospho-D-glycerate binding.
FT REGION 89 92 2,3-bisphospho-D-glycerate binding.
FT REGION 116 117 2,3-diphosphoglyceric acid binding.
FT REGION 188 190 2,3-bisphospho-D-glycerate binding.
FT ACT_SITE 11 11 Tele-phosphohistidine intermediate.
FT ACT_SITE 188 188
FT BINDING 17 17 2,3-bisphospho-D-glycerate.
FT BINDING 62 62 2,3-bisphospho-D-glycerate.
FT BINDING 100 100 2,3-bisphospho-D-glycerate.
FT SITE 29 29 Not glycated.
FT SITE 46 46 Not glycated.
FT SITE 143 143 Not glycated.
FT SITE 181 181 Not glycated.
FT SITE 246 246 Not glycated.
FT SITE 247 247 Not glycated.
FT SITE 253 253 Not glycated.
FT SITE 258 258 Not glycated.
FT SITE 259 259 Not glycated.
FT MOD_RES 2 2 N-acetylserine.
FT CARBOHYD 3 3 N-linked (Glc) (glycation); in vitro.
FT CARBOHYD 5 5 N-linked (Glc) (glycation); in vitro.
FT CARBOHYD 18 18 N-linked (Glc) (glycation); in vitro.
FT CARBOHYD 43 43 N-linked (Glc) (glycation); in vitro.
FT CARBOHYD 159 159 N-linked (Glc) (glycation).
FT CARBOHYD 197 197 N-linked (Glc) (glycation); in vitro.
FT VARIANT 62 62 R -> Q (in BPGMD).
FT /FTId=VAR_065367.
FT VARIANT 90 90 R -> C (in BPGMD; mutation identified at
FT protein level; marked decrease in
FT synthase and mutase activities; no effect
FT on phosphatase activity).
FT /FTId=VAR_065368.
FT STRAND 4 10
FT HELIX 15 18
FT HELIX 32 47
FT STRAND 53 57
FT HELIX 61 74
FT STRAND 81 83
FT HELIX 85 87
FT HELIX 93 95
FT HELIX 100 107
FT HELIX 109 117
FT HELIX 133 137
FT HELIX 140 142
FT STRAND 144 147
FT HELIX 149 151
FT HELIX 158 172
FT HELIX 174 178
FT STRAND 183 187
FT HELIX 189 200
FT HELIX 206 209
FT STRAND 218 222
FT STRAND 228 230
FT HELIX 238 250
SQ SEQUENCE 259 AA; 30005 MW; A2AF1D6F2985A3B5 CRC64;
MSKYKLIMLR HGEGAWNKEN RFCSWVDQKL NSEGMEEARN CGKQLKALNF EFDLVFTSVL
NRSIHTAWLI LEELGQEWVP VESSWRLNER HYGALIGLNR EQMALNHGEE QVRLWRRSYN
VTPPPIEESH PYYQEIYNDR RYKVCDVPLD QLPRSESLKD VLERLLPYWN ERIAPEVLRG
KTILISAHGN SSRALLKHLE GISDEDIINI TLPTGVPILL ELDENLRAVG PHQFLGDQEA
IQAAIKKVED QGKVKQAKK
//
ID PMGE_HUMAN Reviewed; 259 AA.
AC P07738; A4D1N9;
DT 01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 2.
DT 22-JAN-2014, entry version 147.
DE RecName: Full=Bisphosphoglycerate mutase;
DE Short=BPGM;
DE EC=5.4.2.4;
DE AltName: Full=2,3-bisphosphoglycerate mutase, erythrocyte;
DE AltName: Full=2,3-bisphosphoglycerate synthase;
DE EC=3.1.3.13;
DE EC=5.4.2.11;
DE AltName: Full=2,3-diphosphoglycerate mutase;
DE Short=DPGM;
DE AltName: Full=BPG-dependent PGAM;
GN Name=BPGM;
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 PARTIAL PROTEIN SEQUENCE, MASS SPECTROMETRY, IDENTIFICATION OF VARIANT
RP BPGMD CYS-90, AND CHARACTERIZATION OF VARIANT BPGMD CYS-90.
RX PubMed=2542247;
RA Rosa R., Blouquit Y., Calvin M.C., Prome D., Prome J.C., Rosa J.;
RT "Isolation, characterization, and structure of a mutant 89 ArgTO:
RT bisphosphoglycerate mutase. Implication of the active site in the
RT mutation.";
RL J. Biol. Chem. 264:7837-7843(1989).
RN [2]
RP PRELIMINARY PROTEIN SEQUENCE OF 2-259, CLEAVAGE OF INITIATOR
RP METHIONINE, AND TISSUE SPECIFICITY.
RX PubMed=6313356;
RA Haggarty N.W., Dunbar B., Fothergill L.A.;
RT "The complete amino acid sequence of human erythrocyte
RT diphosphoglycerate mutase.";
RL EMBO J. 2:1213-1220(1983).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RX PubMed=3023066;
RA Joulin V., Peduzzi J., Romeo P.-H., Rosa R., Valentin C., Dubart A.,
RA Lapeyre B., Blouquit Y., Garel M.-C., Goossens M., Rosa J.,
RA Cohen-Solal M.;
RT "Molecular cloning and sequencing of the human erythrocyte 2,3-
RT bisphosphoglycerate mutase cDNA: revised amino acid sequence.";
RL EMBO J. 5:2275-2283(1986).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3036106;
RA Cohen-Solal M., Joulin V., Romeo P.-H., Rosa R., Valentin C.,
RA Garel M.-C., Rosa J.;
RT "Molecular cloning of the human 2,3-bisphosphoglycerate mutase cDNA
RT and revised amino acid sequence.";
RL Biomed. Biochim. Acta 46:S126-S130(1987).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2844822;
RA Joulin V., Garel M.-C., le Boulch P., Valentin C., Rosa R., Rosa J.,
RA Cohen-Solal M.;
RT "Isolation and characterization of the human 2,3-bisphosphoglycerate
RT mutase gene.";
RL J. Biol. Chem. 263:15785-15790(1988).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Heart;
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 [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12690205; DOI=10.1126/science.1083423;
RA Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K.,
RA Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R.,
RA Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A.,
RA Kanematsu E., Gentles S., Christopoulos C.C., Choufani S.,
RA Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z.,
RA Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C.,
RA Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J.,
RA Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F.,
RA Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F.,
RA Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H.,
RA Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G.,
RA Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P.,
RA Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J.,
RA Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F.,
RA Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B.,
RA Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H.,
RA Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W.,
RA Mural R.J., Adams M.D., Tsui L.-C.;
RT "Human chromosome 7: DNA sequence and biology.";
RL Science 300:767-772(2003).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton 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].
RC TISSUE=Colon;
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 PROTEIN SEQUENCE OF 2-46; 144-168 AND 182-206, GLYCATION AT LYS-3;
RP LYS-5; LYS-18; LYS-43; LYS-159 AND LYS-197, AND LACK OF GLYCATION AT
RP LYS-29; LYS-46; LYS-143; LYS-181; LYS-246; LYS-247; LYS-253; LYS-258
RP AND LYS-259.
RX PubMed=9832630; DOI=10.1093/oxfordjournals.jbchem.a022243;
RA Fujita T., Suzuki K., Tada T., Yoshihara Y., Hamaoka R., Uchida K.,
RA Matuo Y., Sasaki T., Hanafusa T., Taniguchi N.;
RT "Human erythrocyte bisphosphoglycerate mutase: inactivation by
RT glycation in vivo and in vitro.";
RL J. Biochem. 124:1237-1244(1998).
RN [11]
RP PROTEIN SEQUENCE OF 104-114.
RX PubMed=8440681;
RA Stafforini D.M., Rollins E.N., Prescott S.M., McIntyre T.M.;
RT "The platelet-activating factor acetylhydrolase from human
RT erythrocytes. Purification and properties.";
RL J. Biol. Chem. 268:3857-3865(1993).
RN [12]
RP ENZYME REGULATION.
RX PubMed=10477269; DOI=10.1042/0264-6021:3420581;
RA Mulquiney P.J., Kuchel P.W.;
RT "Model of 2,3-bisphosphoglycerate metabolism in the human erythrocyte
RT based on detailed enzyme kinetic equations: equations and parameter
RT refinement.";
RL Biochem. J. 342:581-596(1999).
RN [13]
RP TISSUE SPECIFICITY.
RX PubMed=16246416; DOI=10.1016/j.placenta.2005.08.010;
RA Pritlove D.C., Gu M., Boyd C.A., Randeva H.S., Vatish M.;
RT "Novel placental expression of 2,3-bisphosphoglycerate mutase.";
RL Placenta 27:924-927(2006).
RN [14]
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 [15]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
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 [16]
RP 3D-STRUCTURE MODELING.
RX PubMed=1387804; DOI=10.1016/0300-9084(92)90149-9;
RA Craescu C.T., Schaad O., Garel M.-C., Rosa R., Edelstein S.J.;
RT "Structural modeling of the human erythrocyte bisphosphoglycerate
RT mutase.";
RL Biochimie 74:519-526(1992).
RN [17]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 1-258 IN COMPLEXES WITH
RP 3-PHOSPHO-D-GLYCERATE AND 2,3-BISPHOSPHO-D-GLYCERATE, SUBUNIT, AND
RP ACTIVE SITE.
RX PubMed=17052986; DOI=10.1074/jbc.M606421200;
RA Wang Y., Liu L., Wei Z., Cheng Z., Lin Y., Gong W.;
RT "Seeing the process of histidine phosphorylation in human
RT bisphosphoglycerate mutase.";
RL J. Biol. Chem. 281:39642-39648(2006).
RN [18]
RP X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS), AND ENZYME REGULATION.
RX PubMed=21045285; DOI=10.1107/S1744309110035475;
RA Patterson A., Price N.C., Nairn J.;
RT "Unliganded structure of human bisphosphoglycerate mutase reveals
RT side-chain movements induced by ligand binding.";
RL Acta Crystallogr. F 66:1415-1420(2010).
RN [19]
RP VARIANT BPGMD CYS-90.
RX PubMed=1421379;
RA Lemarchandel V., Joulin V., Valentin C., Rosa R., Galacteros F.,
RA Rosa J., Cohen-Solal M.;
RT "Compound heterozygosity in a complete erythrocyte bisphosphoglycerate
RT mutase deficiency.";
RL Blood 80:2643-2649(1992).
RN [20]
RP VARIANT BPGMD GLN-62.
RX PubMed=15054810; DOI=10.1002/ajh.20014;
RA Hoyer J.D., Allen S.L., Beutler E., Kubik K., West C., Fairbanks V.F.;
RT "Erythrocytosis due to bisphosphoglycerate mutase deficiency with
RT concurrent glucose-6-phosphate dehydrogenase (G-6-PD) deficiency.";
RL Am. J. Hematol. 75:205-208(2004).
CC -!- FUNCTION: Plays a major role in regulating hemoglobin oxygen
CC affinity by controlling the levels of its allosteric effector 2,3-
CC bisphosphoglycerate (2,3-BPG). Also exhibits mutase (EC 5.4.2.1)
CC and phosphatase (EC 3.1.3.13) activities.
CC -!- CATALYTIC ACTIVITY: 3-phospho-D-glyceroyl phosphate = 2,3-
CC bisphospho-D-glycerate.
CC -!- CATALYTIC ACTIVITY: 2-phospho-D-glycerate = 3-phospho-D-glycerate.
CC -!- CATALYTIC ACTIVITY: 2,3-bisphospho-D-glycerate + H(2)O = 3-
CC phospho-D-glycerate + phosphate.
CC -!- ENZYME REGULATION: At alkaline pH BPGM favors the synthase
CC reaction; however, at lower pH the phosphatase reaction is
CC dominant. Inhibited by citrate.
CC -!- SUBUNIT: Homodimer.
CC -!- TISSUE SPECIFICITY: Expressed in red blood cells. Expressed in
CC non-erythroid cells of the placenta; present in the
CC syncytiotrophoblast layer of the placental villi at the feto-
CC maternal interface (at protein level).
CC -!- PTM: Glycation of Lys-159 in diabetic patients inactivates the
CC enzyme.
CC -!- DISEASE: Bisphosphoglycerate mutase deficiency (BPGMD)
CC [MIM:222800]: A disease characterized by hemolytic anemia,
CC splenomegaly, cholelithiasis and cholecystitis. Note=The disease
CC is caused by mutations affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the phosphoglycerate mutase family. BPG-
CC dependent PGAM subfamily.
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DR EMBL; X04327; CAA27858.1; -; mRNA.
DR EMBL; M23068; AAA51840.1; -; Genomic_DNA.
DR EMBL; M23067; AAA51840.1; JOINED; Genomic_DNA.
DR EMBL; AK315439; BAG37827.1; -; mRNA.
DR EMBL; CH236950; EAL24067.1; -; Genomic_DNA.
DR EMBL; CH471070; EAW83821.1; -; Genomic_DNA.
DR EMBL; BC017050; AAH17050.1; -; mRNA.
DR PIR; A31999; PMHUBM.
DR RefSeq; NP_001715.1; NM_001724.4.
DR RefSeq; NP_954655.1; NM_199186.2.
DR RefSeq; XP_005250602.1; XM_005250545.1.
DR UniGene; Hs.198365; -.
DR PDB; 1T8P; X-ray; 2.50 A; A/B=1-259.
DR PDB; 2A9J; X-ray; 2.00 A; A/B=1-259.
DR PDB; 2F90; X-ray; 2.00 A; A/B=1-259.
DR PDB; 2H4X; X-ray; 1.85 A; A/B=1-259.
DR PDB; 2H4Z; X-ray; 2.00 A; A/B=1-259.
DR PDB; 2H52; X-ray; 2.00 A; A/B=1-259.
DR PDB; 2HHJ; X-ray; 1.50 A; A/B=1-259.
DR PDB; 3NFY; X-ray; 1.94 A; A/B=1-259.
DR PDBsum; 1T8P; -.
DR PDBsum; 2A9J; -.
DR PDBsum; 2F90; -.
DR PDBsum; 2H4X; -.
DR PDBsum; 2H4Z; -.
DR PDBsum; 2H52; -.
DR PDBsum; 2HHJ; -.
DR PDBsum; 3NFY; -.
DR ProteinModelPortal; P07738; -.
DR SMR; P07738; 2-256.
DR IntAct; P07738; 8.
DR STRING; 9606.ENSP00000342032; -.
DR PhosphoSite; P07738; -.
DR DMDM; 130350; -.
DR REPRODUCTION-2DPAGE; IPI00215979; -.
DR PaxDb; P07738; -.
DR PeptideAtlas; P07738; -.
DR PRIDE; P07738; -.
DR DNASU; 669; -.
DR Ensembl; ENST00000344924; ENSP00000342032; ENSG00000172331.
DR Ensembl; ENST00000393132; ENSP00000376840; ENSG00000172331.
DR Ensembl; ENST00000418040; ENSP00000399838; ENSG00000172331.
DR GeneID; 669; -.
DR KEGG; hsa:669; -.
DR UCSC; uc003vrv.3; human.
DR CTD; 669; -.
DR GeneCards; GC07P134331; -.
DR HGNC; HGNC:1093; BPGM.
DR HPA; HPA016493; -.
DR HPA; HPA028735; -.
DR MIM; 222800; phenotype.
DR MIM; 613896; gene.
DR neXtProt; NX_P07738; -.
DR Orphanet; 714; Hemolytic anemia due to diphosphoglycerate mutase deficiency.
DR PharmGKB; PA25401; -.
DR eggNOG; COG0588; -.
DR HOGENOM; HOG000221682; -.
DR HOVERGEN; HBG027528; -.
DR InParanoid; P07738; -.
DR KO; K01837; -.
DR OMA; NLHAVGP; -.
DR OrthoDB; EOG7XM2ZV; -.
DR PhylomeDB; P07738; -.
DR BioCyc; MetaCyc:HS10491-MONOMER; -.
DR SABIO-RK; P07738; -.
DR ChiTaRS; BPGM; human.
DR EvolutionaryTrace; P07738; -.
DR GenomeRNAi; 669; -.
DR NextBio; 2738; -.
DR PRO; PR:P07738; -.
DR ArrayExpress; P07738; -.
DR Bgee; P07738; -.
DR CleanEx; HS_BPGM; -.
DR Genevestigator; P07738; -.
DR GO; GO:0004083; F:bisphosphoglycerate 2-phosphatase activity; IEA:UniProtKB-EC.
DR GO; GO:0004082; F:bisphosphoglycerate mutase activity; TAS:ProtInc.
DR GO; GO:0004619; F:phosphoglycerate mutase activity; IEA:InterPro.
DR GO; GO:0005975; P:carbohydrate metabolic process; NAS:ProtInc.
DR GO; GO:0006096; P:glycolysis; IEA:UniProtKB-KW.
DR GO; GO:0007585; P:respiratory gaseous exchange; TAS:ProtInc.
DR InterPro; IPR013078; His_Pase_superF_clade-1.
DR InterPro; IPR001345; PG/BPGM_mutase_AS.
DR InterPro; IPR005952; Phosphogly_mut1.
DR PANTHER; PTHR11931; PTHR11931; 1.
DR Pfam; PF00300; His_Phos_1; 1.
DR SMART; SM00855; PGAM; 1.
DR TIGRFAMs; TIGR01258; pgm_1; 1.
DR PROSITE; PS00175; PG_MUTASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Complete proteome;
KW Direct protein sequencing; Disease mutation; Glycation; Glycolysis;
KW Glycoprotein; Hereditary hemolytic anemia; Hydrolase; Isomerase;
KW Reference proteome.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 259 Bisphosphoglycerate mutase.
FT /FTId=PRO_0000179834.
FT REGION 23 24 2,3-bisphospho-D-glycerate binding.
FT REGION 89 92 2,3-bisphospho-D-glycerate binding.
FT REGION 116 117 2,3-diphosphoglyceric acid binding.
FT REGION 188 190 2,3-bisphospho-D-glycerate binding.
FT ACT_SITE 11 11 Tele-phosphohistidine intermediate.
FT ACT_SITE 188 188
FT BINDING 17 17 2,3-bisphospho-D-glycerate.
FT BINDING 62 62 2,3-bisphospho-D-glycerate.
FT BINDING 100 100 2,3-bisphospho-D-glycerate.
FT SITE 29 29 Not glycated.
FT SITE 46 46 Not glycated.
FT SITE 143 143 Not glycated.
FT SITE 181 181 Not glycated.
FT SITE 246 246 Not glycated.
FT SITE 247 247 Not glycated.
FT SITE 253 253 Not glycated.
FT SITE 258 258 Not glycated.
FT SITE 259 259 Not glycated.
FT MOD_RES 2 2 N-acetylserine.
FT CARBOHYD 3 3 N-linked (Glc) (glycation); in vitro.
FT CARBOHYD 5 5 N-linked (Glc) (glycation); in vitro.
FT CARBOHYD 18 18 N-linked (Glc) (glycation); in vitro.
FT CARBOHYD 43 43 N-linked (Glc) (glycation); in vitro.
FT CARBOHYD 159 159 N-linked (Glc) (glycation).
FT CARBOHYD 197 197 N-linked (Glc) (glycation); in vitro.
FT VARIANT 62 62 R -> Q (in BPGMD).
FT /FTId=VAR_065367.
FT VARIANT 90 90 R -> C (in BPGMD; mutation identified at
FT protein level; marked decrease in
FT synthase and mutase activities; no effect
FT on phosphatase activity).
FT /FTId=VAR_065368.
FT STRAND 4 10
FT HELIX 15 18
FT HELIX 32 47
FT STRAND 53 57
FT HELIX 61 74
FT STRAND 81 83
FT HELIX 85 87
FT HELIX 93 95
FT HELIX 100 107
FT HELIX 109 117
FT HELIX 133 137
FT HELIX 140 142
FT STRAND 144 147
FT HELIX 149 151
FT HELIX 158 172
FT HELIX 174 178
FT STRAND 183 187
FT HELIX 189 200
FT HELIX 206 209
FT STRAND 218 222
FT STRAND 228 230
FT HELIX 238 250
SQ SEQUENCE 259 AA; 30005 MW; A2AF1D6F2985A3B5 CRC64;
MSKYKLIMLR HGEGAWNKEN RFCSWVDQKL NSEGMEEARN CGKQLKALNF EFDLVFTSVL
NRSIHTAWLI LEELGQEWVP VESSWRLNER HYGALIGLNR EQMALNHGEE QVRLWRRSYN
VTPPPIEESH PYYQEIYNDR RYKVCDVPLD QLPRSESLKD VLERLLPYWN ERIAPEVLRG
KTILISAHGN SSRALLKHLE GISDEDIINI TLPTGVPILL ELDENLRAVG PHQFLGDQEA
IQAAIKKVED QGKVKQAKK
//
MIM
222800
*RECORD*
*FIELD* NO
222800
*FIELD* TI
#222800 BISPHOSPHOGLYCERATE MUTASE DEFICIENCY
;;BISPHOSPHOGLYCEROMUTASE DEFICIENCY;;
read moreBPGM DEFICIENCY;;
DIPHOSPHOGLYCERATE MUTASE DEFICIENCY OF ERYTHROCYTE;;
DPGM DEFICIENCY
*FIELD* TX
A number sign (#) is used with this entry because erythrocyte
bisphosphoglycerate mutase deficiency can be caused by compound
heterozygous mutation in the BPGM gene (613896), which encodes a
multifunctional enzyme, on chromosome 7q31-q34.
CLINICAL FEATURES
Schroter (1965) described severe hemolytic anemia in an infant. Although
the proband's blood could not be studied because of multiple
transfusions, the erythrocytes of the consanguineous parents, the sister
and the father's mother showed activity of 2,3-diphosphoglycerate mutase
about half of normal. The family of Bowdler and Prankerd (1964) is
puzzling in that father and son had hemolytic anemia for which
splenectomy was performed. In father and son, Labie et al. (1970) found
a decrease in DPGM by about 50%. An increase in oxygen affinity of
hemoglobin was observed. Schroter (1965) observed heterozygotes in 3
generations including both parents of a homozygous child with hemolytic
anemia.
Rosa et al. (1978) described a French family in which a man and his 3
sisters had erythrocytosis and complete deficiency of
bisphosphoglycerate mutase. As a consequence, the affinity of his red
cells for oxygen was increased. Hemoglobin concentration was 19.0 g per
dl. The morphology of his red cells was normal and there was no evidence
of hemolysis. Low levels of red cell 2,3-DPG prompted assay of the
enzyme.
Scott and Wright (1982) found DPGM to be polymorphic in 4 Alaskan ethnic
groups. Hemoglobin and hematocrit were elevated in all deficient
persons. Thus, both hemolytic anemia and polycythemia have been observed
with deficiency of DPGM.
Galacteros et al. (1984) reported 2 families; in one, 3 sisters and a
brother were homozygotes and all 3 offspring of 2 of them were
heterozygotes with male-to-male transmission. Diphosphoglycerate
phosphatase activity paralleled DPGM activity in all subjects.
MOLECULAR GENETICS
In a patient with complete deficiency of erythrocyte BPGM reported by
Rosa et al. (1978), Rosa et al. (1989) identified a heterozygous
missense mutation in the BPGM gene (613896.0001). Lemarchandel et al.
(1992) studied further the family originally reported by Rosa et al.
(1978). They found that the affected individuals were, in fact, compound
heterozygous for the R89C mutation and a deletion of nucleotide 205C or
206C (amino acid 19) (613896.0002).
*FIELD* SA
Lohr and Waller (1963); Rosa et al. (1973)
*FIELD* RF
1. Bowdler, A. J.; Prankerd, T. A. J.: Studies in congenital non-spherocytic
haemolytic anaemias with specific enzyme defects. Acta Haemat. 31:
65-78, 1964.
2. Galacteros, F.; Rosa, R.; Prehu, M. O.; Najean, Y.; Calvin, M.
C.: Deficit en diphosphoglycerate mutase: nouveaux cas associes a
une polyglobulie. Nouv. Rev. Franc. Hemat. 26: 69-74, 1984.
3. Labie, D.; Leroux, J.-P.; Najman, A.; Reyrolle, C.: Familial diphosphoglycerate
mutase deficiency: influence on the oxygen affinity curves of hemoglobin. FEBS
Lett. 9: 37-40, 1970.
4. Lemarchandel, V.; Joulin, V.; Valentin, C.; Rosa, R.; Galacteros,
F.; Rosa, J.; Cohen-Solal, M.: Compound heterozygosity in a complete
erythrocyte bisphosphoglycerate mutase deficiency. Blood 80: 2643-2649,
1992.
5. Lohr, G. W.; Waller, H. D.: Zur Biochemie einiger angeborener
haemolytischer Anaemien. Folia Haemat. 8: 377-397, 1963.
6. Rosa, R.; Audit, I.; Rosa, J.: Diphosphoglycerate mutase and 2,3-diphosphoglycerate
phosphatase activities of red cells: comparative electrophoretic study. Biochem.
Biophys. Res. Commun. 51: 536-542, 1973.
7. Rosa, R.; Blouquit, Y.; Calvin, M.-C.; Prome, D.; Prome, J.-C.;
Rosa, J.: Isolation, characterization, and structure of a mutant
89 arg-to-cys bisphosphoglycerate mutase: implication of the active
site in the mutation. J. Biol. Chem. 264: 7837-7843, 1989.
8. Rosa, R.; Prehu, M.-O.; Beuzard, Y.; Rosa, J.: The first case
of a complete deficiency of diphosphoglycerate mutase in human erythrocytes. J.
Clin. Invest. 62: 907-915, 1978.
9. Schroter, W.: Kongenitale nichtsphaerocytaere haemolytische Anaemie
bei 2,3-Diphosphoglyceratmutasemangel der Erythrocyten im fruehen
Saeuglingsalter. Klin. Wschr. 43: 1147-1153, 1965.
10. Scott, E. M.; Wright, R. C.: An alternate method for demonstration
of bisphosphoglyceromutase (DPGM) on starch gels. Am. J. Hum. Genet. 34:
1013-1015, 1982.
*FIELD* CS
Skin:
Jaundice
GI:
Splenomegaly;
Cholelithiasis;
Cholecystitis
Heme:
Nonspherocytic hemolytic anemia;
Normocytic anemia;
Normochromic anemia;
Normal osmotic fragility
Lab:
Diphosphoglycerate mutase deficiency
Inheritance:
Autosomal recessive
*FIELD* CN
Carol A. Bocchini - reorganized: 4/13/2011
*FIELD* CD
Victor A. McKusick: 6/3/1986
*FIELD* ED
carol: 04/13/2011
terry: 4/13/2011
carol: 4/13/2011
carol: 4/8/2011
terry: 6/9/2005
alopez: 3/17/2004
mark: 6/16/1997
warfield: 3/11/1994
mimadm: 2/19/1994
carol: 1/28/1993
carol: 1/5/1993
supermim: 3/16/1992
carol: 3/3/1992
*RECORD*
*FIELD* NO
222800
*FIELD* TI
#222800 BISPHOSPHOGLYCERATE MUTASE DEFICIENCY
;;BISPHOSPHOGLYCEROMUTASE DEFICIENCY;;
read moreBPGM DEFICIENCY;;
DIPHOSPHOGLYCERATE MUTASE DEFICIENCY OF ERYTHROCYTE;;
DPGM DEFICIENCY
*FIELD* TX
A number sign (#) is used with this entry because erythrocyte
bisphosphoglycerate mutase deficiency can be caused by compound
heterozygous mutation in the BPGM gene (613896), which encodes a
multifunctional enzyme, on chromosome 7q31-q34.
CLINICAL FEATURES
Schroter (1965) described severe hemolytic anemia in an infant. Although
the proband's blood could not be studied because of multiple
transfusions, the erythrocytes of the consanguineous parents, the sister
and the father's mother showed activity of 2,3-diphosphoglycerate mutase
about half of normal. The family of Bowdler and Prankerd (1964) is
puzzling in that father and son had hemolytic anemia for which
splenectomy was performed. In father and son, Labie et al. (1970) found
a decrease in DPGM by about 50%. An increase in oxygen affinity of
hemoglobin was observed. Schroter (1965) observed heterozygotes in 3
generations including both parents of a homozygous child with hemolytic
anemia.
Rosa et al. (1978) described a French family in which a man and his 3
sisters had erythrocytosis and complete deficiency of
bisphosphoglycerate mutase. As a consequence, the affinity of his red
cells for oxygen was increased. Hemoglobin concentration was 19.0 g per
dl. The morphology of his red cells was normal and there was no evidence
of hemolysis. Low levels of red cell 2,3-DPG prompted assay of the
enzyme.
Scott and Wright (1982) found DPGM to be polymorphic in 4 Alaskan ethnic
groups. Hemoglobin and hematocrit were elevated in all deficient
persons. Thus, both hemolytic anemia and polycythemia have been observed
with deficiency of DPGM.
Galacteros et al. (1984) reported 2 families; in one, 3 sisters and a
brother were homozygotes and all 3 offspring of 2 of them were
heterozygotes with male-to-male transmission. Diphosphoglycerate
phosphatase activity paralleled DPGM activity in all subjects.
MOLECULAR GENETICS
In a patient with complete deficiency of erythrocyte BPGM reported by
Rosa et al. (1978), Rosa et al. (1989) identified a heterozygous
missense mutation in the BPGM gene (613896.0001). Lemarchandel et al.
(1992) studied further the family originally reported by Rosa et al.
(1978). They found that the affected individuals were, in fact, compound
heterozygous for the R89C mutation and a deletion of nucleotide 205C or
206C (amino acid 19) (613896.0002).
*FIELD* SA
Lohr and Waller (1963); Rosa et al. (1973)
*FIELD* RF
1. Bowdler, A. J.; Prankerd, T. A. J.: Studies in congenital non-spherocytic
haemolytic anaemias with specific enzyme defects. Acta Haemat. 31:
65-78, 1964.
2. Galacteros, F.; Rosa, R.; Prehu, M. O.; Najean, Y.; Calvin, M.
C.: Deficit en diphosphoglycerate mutase: nouveaux cas associes a
une polyglobulie. Nouv. Rev. Franc. Hemat. 26: 69-74, 1984.
3. Labie, D.; Leroux, J.-P.; Najman, A.; Reyrolle, C.: Familial diphosphoglycerate
mutase deficiency: influence on the oxygen affinity curves of hemoglobin. FEBS
Lett. 9: 37-40, 1970.
4. Lemarchandel, V.; Joulin, V.; Valentin, C.; Rosa, R.; Galacteros,
F.; Rosa, J.; Cohen-Solal, M.: Compound heterozygosity in a complete
erythrocyte bisphosphoglycerate mutase deficiency. Blood 80: 2643-2649,
1992.
5. Lohr, G. W.; Waller, H. D.: Zur Biochemie einiger angeborener
haemolytischer Anaemien. Folia Haemat. 8: 377-397, 1963.
6. Rosa, R.; Audit, I.; Rosa, J.: Diphosphoglycerate mutase and 2,3-diphosphoglycerate
phosphatase activities of red cells: comparative electrophoretic study. Biochem.
Biophys. Res. Commun. 51: 536-542, 1973.
7. Rosa, R.; Blouquit, Y.; Calvin, M.-C.; Prome, D.; Prome, J.-C.;
Rosa, J.: Isolation, characterization, and structure of a mutant
89 arg-to-cys bisphosphoglycerate mutase: implication of the active
site in the mutation. J. Biol. Chem. 264: 7837-7843, 1989.
8. Rosa, R.; Prehu, M.-O.; Beuzard, Y.; Rosa, J.: The first case
of a complete deficiency of diphosphoglycerate mutase in human erythrocytes. J.
Clin. Invest. 62: 907-915, 1978.
9. Schroter, W.: Kongenitale nichtsphaerocytaere haemolytische Anaemie
bei 2,3-Diphosphoglyceratmutasemangel der Erythrocyten im fruehen
Saeuglingsalter. Klin. Wschr. 43: 1147-1153, 1965.
10. Scott, E. M.; Wright, R. C.: An alternate method for demonstration
of bisphosphoglyceromutase (DPGM) on starch gels. Am. J. Hum. Genet. 34:
1013-1015, 1982.
*FIELD* CS
Skin:
Jaundice
GI:
Splenomegaly;
Cholelithiasis;
Cholecystitis
Heme:
Nonspherocytic hemolytic anemia;
Normocytic anemia;
Normochromic anemia;
Normal osmotic fragility
Lab:
Diphosphoglycerate mutase deficiency
Inheritance:
Autosomal recessive
*FIELD* CN
Carol A. Bocchini - reorganized: 4/13/2011
*FIELD* CD
Victor A. McKusick: 6/3/1986
*FIELD* ED
carol: 04/13/2011
terry: 4/13/2011
carol: 4/13/2011
carol: 4/8/2011
terry: 6/9/2005
alopez: 3/17/2004
mark: 6/16/1997
warfield: 3/11/1994
mimadm: 2/19/1994
carol: 1/28/1993
carol: 1/5/1993
supermim: 3/16/1992
carol: 3/3/1992
MIM
613896
*RECORD*
*FIELD* NO
613896
*FIELD* TI
*613896 BISPHOSPHOGLYCERATE MUTASE; BPGM
;;2,3-@BISPHOSPHOGLYCERATE PHOSPHATASE;;
2,3-@BPG PHOSPHATASE;;
read more2,3-@DIPHOSPHOGLYCERATE MUTASE; DPGM
*FIELD* TX
DESCRIPTION
The level of 2,3-dephosphoglycerate (DPG), the allosteric ligand of
hemoglobin, is controlled by bisphosphoglycerate mutase (BPGM; EC
5.4.2.4; formerly EC 2.7.5.4.), a multifunctional enzyme specifically
found in the red blood cells of humans and of several animal species.
BPGM synthesizes DPG through its synthase activity and degrades it
through its phosphatase activity. In addition, BPGM has a minor activity
that catalyzes 5% of the reversible conversion of 3-phosphoglycerate, a
reaction mainly catalyzed by a distinct enzyme, phosphoglycerate mutase
(PGAM; see 172250) (summary by Lemarchandel et al., 1992).
CLONING
Chen et al. (1971) described a genetically determined electrophoretic
variant of 2,3-diphosphoglycerate mutase in a Canadian Eskimo family.
The findings in heterozygotes were consistent with the view that the
protein is a dimer of 2 identical subunits.
Rosa et al. (1973, 1978) showed that the DPGM and
2,3-bisphosphoglycerate phosphatase activities of red cells are due to a
single enzyme, bisphosphoglycerate mutase.
Joulin et al. (1986) cloned and sequenced cDNA for human red cell
2,3-bisphosphoglycerate mutase. They presented a revised amino acid
sequence of human BPGM based on the nucleotide sequence data.
BPGM shows some phosphoglycerate mutase activity (Sasaki et al., 1975);
nevertheless, the major portion of PGAM activity in the red cells is
expressed by PGAM (see 172250), a protein genetically distinct from BPGM
but structurally related to it. Both amino acid and cDNA sequence
studies show that BPGM is homologous to PGAM (Joulin et al., 1986;
Yanagawa et al., 1986).
MAPPING
Using a cDNA clone for human BPGM in in situ hybridization experiments,
Joulin et al. (1987) and Barichard et al. (1987) mapped the BPGM gene to
chromosome 7q22-q34.
GENE STRUCTURE
Joulin et al. (1988) isolated the 2,3-bisphosphoglycerate mutase gene
from genomic libraries. By Southern blots and DNA sequencing, they
determined that it extends over 22 kb and contains 3 exons. The second
exon correlates with a functional subdomain of the protein. No GC-rich
sequence or GC box was found in the 5-prime flanking region of the gene.
MOLECULAR GENETICS
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
In a patient with complete deficiency of erythrocyte BPGM (222800)
reported by Rosa et al. (1978), Rosa et al. (1989) identified a
heterozygous missense mutation in the BPGM gene (613896.0001).
Lemarchandel et al. (1992) studied further the family originally
reported by Rosa et al. (1978). They found that the affected individuals
were, in fact, compound heterozygous for the R89C mutation and a
deletion of nucleotide 205C or 206C (amino acid 19) (613896.0002).
*FIELD* AV
.0001
BISPHOSPHOGLYCERATE MUTASE DEFICIENCY, ERYTHROCYTOSIS DUE TO
BPGM, ARG89CYS
Rosa et al. (1989) reported the purification, characterization, and
structural study of an abnormal form of the BPGM enzyme isolated from a
patient, previously reported by Rosa et al. (1978), with erythrocytosis
and undetectable levels of bisphosphoglycerate mutase and
bisphosphosphoglycerate synthase in erythrocytes (222800). The abnormal
enzyme, present at 50% of the level of the normal enzyme as estimated by
immunologic methods, showed elevated electrophoretic mobility. It was
unstable at 55 degrees C. Specific activity of the synthase was 0.57% of
normal and that of the mutase 4.1%. By contrast, the specific
phosphatase activity was not affected by the mutation. However, the
phosphatase activity of the mutated protein was markedly less stimulated
by glycolate-2-phosphate than that of the control. Amino acid sequence
and mass spectrographic analysis demonstrated the substitution of
cysteine for arginine at position 89 (R89C). The data suggested that
arg89 is located at or near the active site of bisphosphoglycerate
mutase and that this residue is probably involved in the binding of
monophosphoglycerates. Rosa et al. (1989) designated this mutation BPGM
Creteil I.
Lemarchandel et al. (1992) studied further the family originally
reported by Rosa et al. (1978). They found that the affected individuals
in this family were, in fact, compound heterozygous for the R89C
mutation and a deletion of nucleotide 205C or 206C (amino acid 19)
(613896.0002). The latter frameshift mutation induced an abnormal coding
sequence that ended prematurely 84 nucleotides downstream and
corresponded to a theoretical abnormal protein sequence of 46 amino
acids, 19 of the amino terminal sequence of BPGM, and an extra sequence
of 27 amino acids. They designated the frameshift mutation BPGM Creteil
II.
.0002
BISPHOSPHOGLYCERATE MUTASE DEFICIENCY
BPGM, 1-BP DEL, 205C
See 613896.0001 and Lemarchandel et al. (1992).
*FIELD* SA
Chen et al. (1977); Scott and Wright (1982)
*FIELD* RF
1. Barichard, F.; Joulin, V.; Henry, I.; Garel, M.-C.; Valentin, C.;
Rosa, R.; Cohen-Solal, M.; Junien, C.: Chromosomal assignment of
the human 2,3-bisphosphoglycerate mutase gene (BPGM) to region 7q34-7q22. Hum.
Genet. 77: 283-285, 1987.
2. Chen, S.-H.; Anderson, J. E.; Giblett, E. R.: Human red cell 2,3-diphosphoglycerate
mutase and monophosphoglycerate mutase: genetic evidence for two separate
loci. Am. J. Hum. Genet. 29: 405-407, 1977.
3. Chen, S.-H.; Anderson, J. E.; Giblett, E. R.: 2,3-Diphosphoglycerate
mutase: its demonstration by electrophoresis and the detection of
a genetic variant. Biochem. Genet. 5: 481-486, 1971.
4. Joulin, V.; Barichard, F.; Henry, I.; Garel, M. C.; Valentin, C.;
Rosa, R.; Cohen-Solal, M.; Junien, C.: Chromosomal assignment of
the human 2,3-bisphosphoglycerate mutase gene (BPGM) to region 7q22-7q34.
(Abstract) Cytogenet. Cell Genet. 46: 635 only, 1987.
5. Joulin, V.; Garel, M.-C.; Le Boulch, P.; Valentin, C.; Rosa, R.;
Rosa, J.; Cohen-Solal, M.: Isolation and characterization of the
human 2,3-bisphosphoglycerate mutase gene. J. Biol. Chem. 263: 15785-15790,
1988.
6. Joulin, V.; Peduzzi, J.; Romeo, P.-H.; Rosa, R.; Valentin, C.;
Dubart, A.; Lapeyre, B.; Blouquit, Y.; Garel, M.-C.; Goossens, M.;
Rosa, J.; Cohen-Solal, M.: Molecular cloning and sequencing of the
human erythrocyte 2,3-bisphosphoglycerate mutase cDNA: revised amino
acid sequence. EMBO J. 5: 2275-2283, 1986.
7. Lemarchandel, V.; Joulin, V.; Valentin, C.; Rosa, R.; Galacteros,
F.; Rosa, J.; Cohen-Solal, M.: Compound heterozygosity in a complete
erythrocyte bisphosphoglycerate mutase deficiency. Blood 80: 2643-2649,
1992.
8. Rosa, R.; Audit, I.; Rosa, J.: Diphosphoglycerate mutase and 2,3-diphosphoglycerate
phosphatase activities of red cells: comparative electrophoretic study. Biochem.
Biophys. Res. Commun. 51: 536-542, 1973.
9. Rosa, R.; Blouquit, Y.; Calvin, M.-C.; Prome, D.; Prome, J.-C.;
Rosa, J.: Isolation, characterization, and structure of a mutant
89 arg-to-cys bisphosphoglycerate mutase: implication of the active
site in the mutation. J. Biol. Chem. 264: 7837-7843, 1989.
10. Rosa, R.; Prehu, M.-O.; Beuzard, Y.; Rosa, J.: The first case
of a complete deficiency of diphosphoglycerate mutase in human erythrocytes. J.
Clin. Invest. 62: 907-915, 1978.
11. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.
12. Sasaki, R.; Ikura, K.; Sugimoto, E.; Chiba, H.: Purification
of bisphosphoglyceromutase, 2,3-bisphosphoglycerate phosphatase and
phosphoglyceromutase from human erythrocytes. Europ. J. Biochem. 50:
581-593, 1975.
13. Scott, E. M.; Wright, R. C.: An alternate method for demonstration
of bisphosphoglyceromutase (DPGM) on starch gels. Am. J. Hum. Genet. 34:
1013-1015, 1982.
14. Yanagawa, S.; Hitomi, K.; Sasaki, R.; Chiba, H.: Isolation and
characterization of cDNA encoding rabbit reticulocyte 2,3-bisphosphoglycerate
synthase. Gene 44: 185-191, 1986.
*FIELD* CD
Carol A. Bocchini: 4/12/2011
*FIELD* ED
carol: 04/13/2011
carol: 4/13/2011
*RECORD*
*FIELD* NO
613896
*FIELD* TI
*613896 BISPHOSPHOGLYCERATE MUTASE; BPGM
;;2,3-@BISPHOSPHOGLYCERATE PHOSPHATASE;;
2,3-@BPG PHOSPHATASE;;
read more2,3-@DIPHOSPHOGLYCERATE MUTASE; DPGM
*FIELD* TX
DESCRIPTION
The level of 2,3-dephosphoglycerate (DPG), the allosteric ligand of
hemoglobin, is controlled by bisphosphoglycerate mutase (BPGM; EC
5.4.2.4; formerly EC 2.7.5.4.), a multifunctional enzyme specifically
found in the red blood cells of humans and of several animal species.
BPGM synthesizes DPG through its synthase activity and degrades it
through its phosphatase activity. In addition, BPGM has a minor activity
that catalyzes 5% of the reversible conversion of 3-phosphoglycerate, a
reaction mainly catalyzed by a distinct enzyme, phosphoglycerate mutase
(PGAM; see 172250) (summary by Lemarchandel et al., 1992).
CLONING
Chen et al. (1971) described a genetically determined electrophoretic
variant of 2,3-diphosphoglycerate mutase in a Canadian Eskimo family.
The findings in heterozygotes were consistent with the view that the
protein is a dimer of 2 identical subunits.
Rosa et al. (1973, 1978) showed that the DPGM and
2,3-bisphosphoglycerate phosphatase activities of red cells are due to a
single enzyme, bisphosphoglycerate mutase.
Joulin et al. (1986) cloned and sequenced cDNA for human red cell
2,3-bisphosphoglycerate mutase. They presented a revised amino acid
sequence of human BPGM based on the nucleotide sequence data.
BPGM shows some phosphoglycerate mutase activity (Sasaki et al., 1975);
nevertheless, the major portion of PGAM activity in the red cells is
expressed by PGAM (see 172250), a protein genetically distinct from BPGM
but structurally related to it. Both amino acid and cDNA sequence
studies show that BPGM is homologous to PGAM (Joulin et al., 1986;
Yanagawa et al., 1986).
MAPPING
Using a cDNA clone for human BPGM in in situ hybridization experiments,
Joulin et al. (1987) and Barichard et al. (1987) mapped the BPGM gene to
chromosome 7q22-q34.
GENE STRUCTURE
Joulin et al. (1988) isolated the 2,3-bisphosphoglycerate mutase gene
from genomic libraries. By Southern blots and DNA sequencing, they
determined that it extends over 22 kb and contains 3 exons. The second
exon correlates with a functional subdomain of the protein. No GC-rich
sequence or GC box was found in the 5-prime flanking region of the gene.
MOLECULAR GENETICS
Data on gene frequencies of allelic variants were tabulated by
Roychoudhury and Nei (1988).
In a patient with complete deficiency of erythrocyte BPGM (222800)
reported by Rosa et al. (1978), Rosa et al. (1989) identified a
heterozygous missense mutation in the BPGM gene (613896.0001).
Lemarchandel et al. (1992) studied further the family originally
reported by Rosa et al. (1978). They found that the affected individuals
were, in fact, compound heterozygous for the R89C mutation and a
deletion of nucleotide 205C or 206C (amino acid 19) (613896.0002).
*FIELD* AV
.0001
BISPHOSPHOGLYCERATE MUTASE DEFICIENCY, ERYTHROCYTOSIS DUE TO
BPGM, ARG89CYS
Rosa et al. (1989) reported the purification, characterization, and
structural study of an abnormal form of the BPGM enzyme isolated from a
patient, previously reported by Rosa et al. (1978), with erythrocytosis
and undetectable levels of bisphosphoglycerate mutase and
bisphosphosphoglycerate synthase in erythrocytes (222800). The abnormal
enzyme, present at 50% of the level of the normal enzyme as estimated by
immunologic methods, showed elevated electrophoretic mobility. It was
unstable at 55 degrees C. Specific activity of the synthase was 0.57% of
normal and that of the mutase 4.1%. By contrast, the specific
phosphatase activity was not affected by the mutation. However, the
phosphatase activity of the mutated protein was markedly less stimulated
by glycolate-2-phosphate than that of the control. Amino acid sequence
and mass spectrographic analysis demonstrated the substitution of
cysteine for arginine at position 89 (R89C). The data suggested that
arg89 is located at or near the active site of bisphosphoglycerate
mutase and that this residue is probably involved in the binding of
monophosphoglycerates. Rosa et al. (1989) designated this mutation BPGM
Creteil I.
Lemarchandel et al. (1992) studied further the family originally
reported by Rosa et al. (1978). They found that the affected individuals
in this family were, in fact, compound heterozygous for the R89C
mutation and a deletion of nucleotide 205C or 206C (amino acid 19)
(613896.0002). The latter frameshift mutation induced an abnormal coding
sequence that ended prematurely 84 nucleotides downstream and
corresponded to a theoretical abnormal protein sequence of 46 amino
acids, 19 of the amino terminal sequence of BPGM, and an extra sequence
of 27 amino acids. They designated the frameshift mutation BPGM Creteil
II.
.0002
BISPHOSPHOGLYCERATE MUTASE DEFICIENCY
BPGM, 1-BP DEL, 205C
See 613896.0001 and Lemarchandel et al. (1992).
*FIELD* SA
Chen et al. (1977); Scott and Wright (1982)
*FIELD* RF
1. Barichard, F.; Joulin, V.; Henry, I.; Garel, M.-C.; Valentin, C.;
Rosa, R.; Cohen-Solal, M.; Junien, C.: Chromosomal assignment of
the human 2,3-bisphosphoglycerate mutase gene (BPGM) to region 7q34-7q22. Hum.
Genet. 77: 283-285, 1987.
2. Chen, S.-H.; Anderson, J. E.; Giblett, E. R.: Human red cell 2,3-diphosphoglycerate
mutase and monophosphoglycerate mutase: genetic evidence for two separate
loci. Am. J. Hum. Genet. 29: 405-407, 1977.
3. Chen, S.-H.; Anderson, J. E.; Giblett, E. R.: 2,3-Diphosphoglycerate
mutase: its demonstration by electrophoresis and the detection of
a genetic variant. Biochem. Genet. 5: 481-486, 1971.
4. Joulin, V.; Barichard, F.; Henry, I.; Garel, M. C.; Valentin, C.;
Rosa, R.; Cohen-Solal, M.; Junien, C.: Chromosomal assignment of
the human 2,3-bisphosphoglycerate mutase gene (BPGM) to region 7q22-7q34.
(Abstract) Cytogenet. Cell Genet. 46: 635 only, 1987.
5. Joulin, V.; Garel, M.-C.; Le Boulch, P.; Valentin, C.; Rosa, R.;
Rosa, J.; Cohen-Solal, M.: Isolation and characterization of the
human 2,3-bisphosphoglycerate mutase gene. J. Biol. Chem. 263: 15785-15790,
1988.
6. Joulin, V.; Peduzzi, J.; Romeo, P.-H.; Rosa, R.; Valentin, C.;
Dubart, A.; Lapeyre, B.; Blouquit, Y.; Garel, M.-C.; Goossens, M.;
Rosa, J.; Cohen-Solal, M.: Molecular cloning and sequencing of the
human erythrocyte 2,3-bisphosphoglycerate mutase cDNA: revised amino
acid sequence. EMBO J. 5: 2275-2283, 1986.
7. Lemarchandel, V.; Joulin, V.; Valentin, C.; Rosa, R.; Galacteros,
F.; Rosa, J.; Cohen-Solal, M.: Compound heterozygosity in a complete
erythrocyte bisphosphoglycerate mutase deficiency. Blood 80: 2643-2649,
1992.
8. Rosa, R.; Audit, I.; Rosa, J.: Diphosphoglycerate mutase and 2,3-diphosphoglycerate
phosphatase activities of red cells: comparative electrophoretic study. Biochem.
Biophys. Res. Commun. 51: 536-542, 1973.
9. Rosa, R.; Blouquit, Y.; Calvin, M.-C.; Prome, D.; Prome, J.-C.;
Rosa, J.: Isolation, characterization, and structure of a mutant
89 arg-to-cys bisphosphoglycerate mutase: implication of the active
site in the mutation. J. Biol. Chem. 264: 7837-7843, 1989.
10. Rosa, R.; Prehu, M.-O.; Beuzard, Y.; Rosa, J.: The first case
of a complete deficiency of diphosphoglycerate mutase in human erythrocytes. J.
Clin. Invest. 62: 907-915, 1978.
11. Roychoudhury, A. K.; Nei, M.: Human Polymorphic Genes: World
Distribution. New York: Oxford Univ. Press (pub.) 1988.
12. Sasaki, R.; Ikura, K.; Sugimoto, E.; Chiba, H.: Purification
of bisphosphoglyceromutase, 2,3-bisphosphoglycerate phosphatase and
phosphoglyceromutase from human erythrocytes. Europ. J. Biochem. 50:
581-593, 1975.
13. Scott, E. M.; Wright, R. C.: An alternate method for demonstration
of bisphosphoglyceromutase (DPGM) on starch gels. Am. J. Hum. Genet. 34:
1013-1015, 1982.
14. Yanagawa, S.; Hitomi, K.; Sasaki, R.; Chiba, H.: Isolation and
characterization of cDNA encoding rabbit reticulocyte 2,3-bisphosphoglycerate
synthase. Gene 44: 185-191, 1986.
*FIELD* CD
Carol A. Bocchini: 4/12/2011
*FIELD* ED
carol: 04/13/2011
carol: 4/13/2011