P07738 (PMGE_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Bisphosphoglycerate mutase
Short name=BPGM
EC=5.4.2.4

Alternative name(s):
2,3-bisphosphoglycerate mutase, erythrocyte
2,3-bisphosphoglycerate synthase
EC=3.1.3.13
EC=5.4.2.1
2,3-diphosphoglycerate mutase
Short name=DPGM
BPG-dependent PGAM

Gene names

Name:

BPGM

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	259 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Plays a major role in regulating hemoglobin oxygen affinity by controlling the levels of its allosteric effector 2,3-bisphosphoglycerate (2,3-BPG). Also exhibits mutase (EC 5.4.2.1) and phosphatase (EC 3.1.3.13) activities.
Catalytic activity	3-phospho-D-glyceroyl phosphate = 2,3-bisphospho-D-glycerate. 2-phospho-D-glycerate = 3-phospho-D-glycerate. 2,3-bisphospho-D-glycerate + H2O = 3-phospho-D-glycerate + phosphate.
Enzyme regulation	At alkaline pH BPGM favors the synthase reaction; however, at lower pH the phosphatase reaction is dominant. Inhibited by citrate. Ref.12
Subunit structure	Homodimer.
Tissue specificity	Expressed in red blood cells. Expressed in non-erythroid cells of the placenta; present in the syncytiotrophoblast layer of the placental villi at the feto-maternal interface (at protein level). Ref.2 Ref.3 Ref.13
Post-translational modification	Glycation of Lys-159 in diabetic patients inactivates the enzyme.
Involvement in disease	Bisphosphoglycerate mutase deficiency (BPGMD) [MIM:222800]: A disease characterized by hemolytic anemia, splenomegaly, cholelithiasis and cholecystitis. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.1 Ref.18 Ref.19
Sequence similarities	Belongs to the phosphoglycerate mutase family. BPG-dependent PGAM subfamily.

Ontologies

Keywords
Biological process	Glycolysis
Disease	Disease mutation Hereditary hemolytic anemia
Molecular function	Hydrolase Isomerase
PTM	Glycation Glycoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	carbohydrate metabolic process Non-traceable author statement Ref.1. Source: ProtInc glycolysis Inferred from electronic annotation. Source: UniProtKB-KW respiratory gaseous exchange Traceable author statement Ref.1. Source: ProtInc
Molecular_function	bisphosphoglycerate 2-phosphatase activity Inferred from electronic annotation. Source: EC bisphosphoglycerate mutase activity Traceable author statement Ref.1. Source: ProtInc phosphoglycerate mutase activity Inferred from electronic annotation. Source: EC
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 259

259

Bisphosphoglycerate mutase

PRO_0000179834

Sites

Active site

11

1

Tele-phosphohistidine intermediate Ref.16

Active site

188

1

Ref.16

Site

29

1

Not glycated

Site

46

1

Not glycated

Site

62

1

Interaction with carboxyl group of phosphoglycerates

Site

143

1

Not glycated

Site

181

1

Not glycated

Site

246

1

Not glycated

Site

247

1

Not glycated

Site

253

1

Not glycated

Site

258

1

Not glycated

Site

259

1

Not glycated

Amino acid modifications

Glycosylation

3

1

N-linked (Glc) (glycation); in vitro Ref.10

Glycosylation

5

1

N-linked (Glc) (glycation); in vitro Ref.10

Glycosylation

18

1

N-linked (Glc) (glycation); in vitro Ref.10

Glycosylation

43

1

N-linked (Glc) (glycation); in vitro Ref.10

Glycosylation

159

1

N-linked (Glc) (glycation) Ref.10

Glycosylation

197

1

N-linked (Glc) (glycation); in vitro Ref.10

Natural variations

Natural variant

62

1

R → Q in BPGMD. Ref.19

VAR_065367

Natural variant

90

1

R → C in BPGMD; mutation identified at protein level; marked decrease in synthase and mutase activities; no effect on phosphatase activity. Ref.1 Ref.18

VAR_065368

Secondary structure

1

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259

Helix Strand Turn

Details...

Beta strand

4 – 10

7

Helix

15 – 18

4

Helix

32 – 47

16

Beta strand

53 – 57

5

Helix

61 – 74

14

Beta strand

81 – 83

3

Helix

85 – 87

3

Helix

93 – 95

3

Helix

100 – 107

8

Helix

109 – 117

9

Helix

133 – 137

5

Helix

140 – 142

3

Beta strand

144 – 147

4

Helix

149 – 151

3

Helix

158 – 172

15

Helix

174 – 178

5

Beta strand

183 – 187

5

Helix

189 – 200

12

Helix

206 – 209

4

Beta strand

218 – 222

5

Beta strand

228 – 230

3

Helix

238 – 250

13

Sequences

	Sequence		Length	Mass (Da)
	P07738 [UniParc]. Last modified January 23, 2007. Version 2. Checksum: A2AF1D6F2985A3B5	FASTA	259	30,005
	10 20 30 40 50 60 MSKYKLIMLR HGEGAWNKEN RFCSWVDQKL NSEGMEEARN CGKQLKALNF EFDLVFTSVL 70 80 90 100 110 120 NRSIHTAWLI LEELGQEWVP VESSWRLNER HYGALIGLNR EQMALNHGEE QVRLWRRSYN 130 140 150 160 170 180 VTPPPIEESH PYYQEIYNDR RYKVCDVPLD QLPRSESLKD VLERLLPYWN ERIAPEVLRG 190 200 210 220 230 240 KTILISAHGN SSRALLKHLE GISDEDIINI TLPTGVPILL ELDENLRAVG PHQFLGDQEA 250 IQAAIKKVED QGKVKQAKK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Isolation, characterization, and structure of a mutant 89 ArgTO: bisphosphoglycerate mutase. Implication of the active site in the mutation." Rosa R., Blouquit Y., Calvin M.C., Prome D., Prome J.C., Rosa J. J. Biol. Chem. 264:7837-7843(1989) [PubMed] [Europe PMC] [Abstract] Cited for: PARTIAL PROTEIN SEQUENCE, MASS SPECTROMETRY, IDENTIFICATION OF VARIANT BPGMD CYS-90, CHARACTERIZATION OF VARIANT BPGMD CYS-90.
[2]	"The complete amino acid sequence of human erythrocyte diphosphoglycerate mutase." Haggarty N.W., Dunbar B., Fothergill L.A. EMBO J. 2:1213-1220(1983) [PubMed] [Europe PMC] [Abstract] Cited for: PRELIMINARY PROTEIN SEQUENCE OF 2-259, TISSUE SPECIFICITY.
[3]	"Molecular cloning and sequencing of the human erythrocyte 2,3-bisphosphoglycerate mutase cDNA: revised amino acid sequence." 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. EMBO J. 5:2275-2283(1986) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[4]	"Molecular cloning of the human 2,3-bisphosphoglycerate mutase cDNA and revised amino acid sequence." Cohen-Solal M., Joulin V., Romeo P.-H., Rosa R., Valentin C., Garel M.-C., Rosa J. Biomed. Biochim. Acta 46:S126-S130(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[5]	"Isolation and characterization of the human 2,3-bisphosphoglycerate mutase gene." Joulin V., Garel M.-C., le Boulch P., Valentin C., Rosa R., Rosa J., Cohen-Solal M. J. Biol. Chem. 263:15785-15790(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[6]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Heart.
[7]	"Human chromosome 7: DNA sequence and biology." Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S. , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C. Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[9]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Colon.
[10]	"Human erythrocyte bisphosphoglycerate mutase: inactivation by glycation in vivo and in vitro." Fujita T., Suzuki K., Tada T., Yoshihara Y., Hamaoka R., Uchida K., Matuo Y., Sasaki T., Hanafusa T., Taniguchi N. J. Biochem. 124:1237-1244(1998) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-46; 144-168 AND 182-206, GLYCATION AT LYS-3; LYS-5; LYS-18; LYS-43; LYS-159 AND LYS-197, LACK OF GLYCATION AT LYS-29; LYS-46; LYS-143; LYS-181; LYS-246; LYS-247; LYS-253; LYS-258 AND LYS-259.
[11]	"The platelet-activating factor acetylhydrolase from human erythrocytes. Purification and properties." Stafforini D.M., Rollins E.N., Prescott S.M., McIntyre T.M. J. Biol. Chem. 268:3857-3865(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 104-114.
[12]	"Model of 2,3-bisphosphoglycerate metabolism in the human erythrocyte based on detailed enzyme kinetic equations: equations and parameter refinement." Mulquiney P.J., Kuchel P.W. Biochem. J. 342:581-596(1999) [PubMed] [Europe PMC] [Abstract] Cited for: ENZYME REGULATION.
[13]	"Novel placental expression of 2,3-bisphosphoglycerate mutase." Pritlove D.C., Gu M., Boyd C.A., Randeva H.S., Vatish M. Placenta 27:924-927(2006) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[14]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[15]	"Structural modeling of the human erythrocyte bisphosphoglycerate mutase." Craescu C.T., Schaad O., Garel M.-C., Rosa R., Edelstein S.J. Biochimie 74:519-526(1992) [PubMed] [Europe PMC] [Abstract] Cited for: 3D-STRUCTURE MODELING.
[16]	"Seeing the process of histidine phosphorylation in human bisphosphoglycerate mutase." Wang Y., Liu L., Wei Z., Cheng Z., Lin Y., Gong W. J. Biol. Chem. 281:39642-39648(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 1-258 IN COMPLEX WITH PHOSPHOGLYCERATE, ACTIVE SITE.
[17]	"Unliganded structure of human bisphosphoglycerate mutase reveals side-chain movements induced by ligand binding." Patterson A., Price N.C., Nairn J. Acta Crystallogr. F 66:1415-1420(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.94 ANGSTROMS), INHIBITION BY CITRATE.
[18]	"Compound heterozygosity in a complete erythrocyte bisphosphoglycerate mutase deficiency." Lemarchandel V., Joulin V., Valentin C., Rosa R., Galacteros F., Rosa J., Cohen-Solal M. Blood 80:2643-2649(1992) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BPGMD CYS-90.
[19]	"Erythrocytosis due to bisphosphoglycerate mutase deficiency with concurrent glucose-6-phosphate dehydrogenase (G-6-PD) deficiency." Hoyer J.D., Allen S.L., Beutler E., Kubik K., West C., Fairbanks V.F. Am. J. Hematol. 75:205-208(2004) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT BPGMD GLN-62.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X04327 mRNA. Translation: CAA27858.1.
M23068, M23067 Genomic DNA. Translation: AAA51840.1.
AK315439 mRNA. Translation: BAG37827.1.
CH236950 Genomic DNA. Translation: EAL24067.1.
CH471070 Genomic DNA. Translation: EAW83821.1.
BC017050 mRNA. Translation: AAH17050.1.

IPI

IPI00215979.

PIR

PMHUBM. A31999.

RefSeq

NP_001715.1. NM_001724.4.
NP_954655.1. NM_199186.2.

UniGene

Hs.198365.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1T8P	X-ray	2.50	A/B	1-259	[»]
2A9J	X-ray	2.00	A/B	1-258	[»]
2F90	X-ray	2.00	A/B	1-259	[»]
2H4X	X-ray	1.85	A/B	1-258	[»]
2H4Z	X-ray	2.00	A/B	1-258	[»]
2H52	X-ray	2.00	A/B	1-258	[»]
2HHJ	X-ray	1.50	A/B	1-258	[»]
3NFY	X-ray	1.94	A/B	1-259	[»]

ProteinModelPortal

P07738.

ModBase

Search...

Protein-protein interaction databases

IntAct

P07738. 8 interactions.

STRING

9606.ENSP00000342032.

PTM databases

PhosphoSite

P07738.

Polymorphism databases

DMDM

130350.

2D gel databases

REPRODUCTION-2DPAGE

IPI00215979.

Proteomic databases

PaxDb

P07738.

PeptideAtlas

P07738.

PRIDE

P07738.

Protocols and materials databases

DNASU

669.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000344924; ENSP00000342032; ENSG00000172331.
ENST00000393132; ENSP00000376840; ENSG00000172331.
ENST00000418040; ENSP00000399838; ENSG00000172331.

GeneID

669.

KEGG

hsa:669.

UCSC

uc003vrv.3. human.

Organism-specific databases

CTD

669.

GeneCards

GC07P134331.

HGNC

HGNC:1093. BPGM.

HPA

HPA016493.
HPA028735.

MIM

222800. phenotype.
613896. gene.

neXtProt

NX_P07738.

Orphanet

714. Hemolytic anemia due to diphosphoglycerate mutase deficiency.

PharmGKB

PA25401.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0588.

HOGENOM

HOG000221682.

HOVERGEN

HBG027528.

InParanoid

P07738.

KO

K01837.

OMA

NLHAVGP.

OrthoDB

EOG454908.

PhylomeDB

P07738.

Enzyme and pathway databases

BioCyc

MetaCyc:HS10491-MONOMER.

SABIO-RK

P07738.

Gene expression databases

ArrayExpress

P07738.

Bgee

P07738.

CleanEx

HS_BPGM.

Genevestigator

P07738.

GermOnline

ENSG00000172331. Homo sapiens.

Family and domain databases

InterPro

IPR013078. His_Pase_superF_clade-1.
IPR001345. PG/BPGM_mutase_AS.
IPR005952. Phosphogly_mut1.
[Graphical view]

PANTHER

PTHR11931. PTHR11931. 1 hit.

Pfam

PF00300. His_Phos_1. 1 hit.
[Graphical view]

SMART

SM00855. PGAM. 1 hit.
[Graphical view]

TIGRFAMs

TIGR01258. pgm_1. 1 hit.

PROSITE

PS00175. PG_MUTASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

BPGM. human.

EvolutionaryTrace

P07738.

GenomeRNAi

669.

NextBio

2738.

SOURCE

Search...

Entry information

Entry name

PMGE_HUMAN

Accession

Primary (citable) accession number: P07738
Secondary accession number(s): A4D1N9

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1988
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 142 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.