Summary: Phosphoglycerate kinase

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Phosphoglycerate kinase Edit Wikipedia article

Phosphoglycerate kinase

Identifiers

Databases

PDB structures

AmiGO / EGO

Search
PMC	articles
PubMed	articles
NCBI	proteins

Phosphoglycerate kinase

Structure of yeast phosphoglycerate kinase.^[1]

Identifiers

Symbol

PGK

Available protein structures:
Pfam	structures
PDB	RCSB PDB; PDBe
PDBsum	structure summary

Phosphoglycerate kinase (EC 2.7.2.3) (PGK) is an enzyme that catalyzes the reversible transfer of a phosphate group from 1,3-bisphosphoglycerate (1,3-BPG) to ADP producing 3-phosphoglycerate (3-PG) and ATP. Like all kinases it is a transferase. PGK is a major enzyme used in glycolysis, in the first ATP-generating step of the glycolytic pathway. In gluconeogenesis, the reaction catalyzed by PGK proceeds in the opposite direction, generating ADP and 1,3-BPG.

In humans, two isozymes of PGK have been so far identified, PGK1 and PGK2. The isozymes have 87-88% identical amino acid sequence identity and though they are structurally and functionally similar, they have different localizations: PGK2, encoded by an autosomal gene, is unique to meiotic and postmeiotic spermatogenic cells, while PGK1, encoded on the X-chromosome, is ubiquitously expressed in all cells.^[2]

[edit] Biological function

Diagram showing glycolytic and gluconeogenic pathways. Note that phosphoglycerate kinase is used in both directions.

PGK is present in all living organisms as one of the two ATP-generating enzymes in glycolysis. In the gluconeogenic pathway, PGK catalyzes the reverse reaction. Under biochemical standard conditions, the glycolytic direction is favored.^[1]

In the Calvin cycle in photosynthetic organisms, PGK catalyzes the phosphorylation of 3-PG, producing 1,3-BPG and ADP, as part of the reactions that regenerate ribulose-1,5-bisphosphate.

PGK has been reported to exhibit thiol reductase activity on plasmin, leading to angiostatin formation, which inhibits angiogenesis and tumor growth. The enzyme was also shown to participate in DNA replication and repair in mammal cell nuclei.^[3]

The human isozyme PGK2, which is only expressed during spermatogenesis, was shown to be essential for sperm function in mice.^[4]

[edit] Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles. ^{[§ 1]}

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Glycolysis and Gluconeogenesis edit

^ The interactive pathway map can be edited at WikiPathways: "GlycolysisGluconeogenesis_WP534".

[edit] Structure

[edit] Overview

PGK is found in all living organisms and its sequence has been highly conserved throughout evolution. The enzyme exists as a 415-residue monomer containing two nearly equal-sized domains that correspond to the N- and C-termini of the protein.^[5] 3-phosphoglycerate (3-PG) binds to the N-terminal, while the nucleotide substrates, MgATP or MgADP, bind to the C-terminal domain of the enzyme. This extended two-domain structure is associated with large-scale 'hinge-bending' conformational changes, similar to those found in hexokinase.^[6] The two proteins of the domain are separated by a cleft and linked by two alpha-helices.^[2] At the core of each domain is a 6-stranded parallel beta-sheet surrounded by alpha helices. The two lobes are capable of folding independently, consistent with the presence of intermediates on the folding pathway with a single domain folded.^[7]^[8] Though the binding of either substrate triggers a conformational change, only through the binding of both substrates does domain closure occur, leading to the transfer of the phosphate group.^[2]

The enzyme has a tendency to exist in the open conformation with short periods of closure and catalysis, which allow for rapid diffusion of substrate and products through the binding sites; the open conformation of PGK is more conformationally stable due to the exposure of a hydrophobic region of the protein upon domain closure.^[7]

[edit] Role of magnesium

Magnesium ions are normally complexed to the phosphate groups the nucleotide substrates of PGK. It is known that in the absence of magnesium, no enzyme activity occurs. ^[9] The bivalent metal assists the enzyme ligands in shielding the bound phosphate group's negative charges, allowing the nucleophilic attack to occur; this charge-stabilization is a typical characteristic of phosphotransfer reaction.^[10] It is theorized that the ion may also encourage domain closure when PGK has bound both substrates.^[9]

[edit] Mechanism

Phosphoglycerate kinase mechanism in glycolysis.

Without either substrate bound, PGK exists in an "open" conformation. After both the triose and nucleotide substrates are bound to the N- and C-terminal domains, respectively, an extensive hinge-bending motion occurs, bringing the domains and their bound substrates into close proximity and leading to a "closed" conformation.^[11] Then, in the case of the forward glycolytic reaction, the beta-phosphate of ADP initiates a nucleophilic attack on the 1-phosphate of 1,3-BPG in an SN2 substitution reaction.^[12] The Lys219 on the enzyme guides the phosphate group to the substrate.

PGK proceeds through a charge-stabilized transition state that is favored over the arrangement of the bound substrate in the closed enzyme because in the transition state, all three phosphate oxygens are stabilized by ligands, as opposed to only two stabilized oxygens in the initial bound state. ^[13]

In the glycolytic pathyway, 1,3-BPG is the phosphate donor and has a high phosphoryl-transfer potential. The PGK-catalyzed transfer of the phosphate group from 1,3-BPG to ADP to yield ATP is powered by the energy from the carbon-oxidation reaction of the previous glycolytic step (converting glyceraldehyde 3-phosphate to 3-phosphoglycerate).

[edit] Regulation

The enzyme is activated by low concentrations of various multivalent anions, such as pyrophosphate, sulfate, phosphate, and citrate. High concentrations of MgATP and 3-PG activates PGK, while Mg2+ at high concentrations non-competitively inhibits the enzyme. ^[14]

PGK exhibits a wide specificity toward nucleotide substrates.^[15] Its activity is inhibited by salicylates, which appear to mimic the enzyme's nucleotide substrate.^[16]

Macromolecular crowding has been shown to increase PGK activity in both computer simluations and in vitro environments simulating a cell interior; as a result of crowding, the enzyme becomes more enyzmatically active and more compact.^[5]

[edit] Disease relevance

Phosphoglycerate kinase (PGK) deficiency is an X-linked recessive trait associated with hemolytic anemia, mental disorders and myopathy in humans.^[17]^[18] Since the trait is X-linked, it is usually fully expressed in males, who have one X chromosome; affected females are typically asymptomatic. ^[18]^[2] The condition results from mutations in Pgk1, the gene encoding PGK1, and twenty mutations have been identified.^[18]^[2] On a molecular level, the mutation in Pgk1 impairs the thermal stability and inhibits the catalytic activity of the enzyme.^[2] PGK is the only enzyme in the immediate glycolytic pathway encoded by an X-linked gene. In the case of hemolytic anemia, PGK deficiency occurs in the erythrocytes. Currently, no definitive treatment exists for PGK deficiency.^[19]

PGK1 overexpression has been associated with gastric cancer and has been found to increase the invasiveness of gastric cancer cells in vitro.^[20] The enzyme is secreted by tumor cells and participates in the angiogenic process, leading to the release of angiostatin and the inhibition of tumor blood vessel growth.^[3]^[21]

Due to its wide specificity towards nucleotide substrates, PGK is known to participate in the phosphorylation and activation of HIV antiretroviral drugs, which are nucleotide-based.^[15]^[22]

[edit] Human isozymes

phosphoglycerate kinase 1
Identifiers
Symbol	PGK1
Entrez	5230
HUGO	8896
OMIM	311800
RefSeq	NM_000291
UniProt	P00558
Other data
EC number	2.7.2.3
Locus	Chr. X q13.3

phosphoglycerate kinase 2
Identifiers
Symbol	PGK2
Entrez	5232
HUGO	8898
OMIM	172270
RefSeq	NM_138733
UniProt	P07205
Other data
EC number	2.7.2.3
Locus	Chr. 6 p21-q12

[edit] References

^ ^a ^b Watson HC, Walker NP, Shaw PJ, et al. (1982). "Sequence and structure of yeast phosphoglycerate kinase". EMBO J. 1 (12): 1635–40. PMC 553262. PMID 6765200.
^ ^a ^b ^c ^d ^e ^f Chiarelli LR, Morera SM, Bianchi P, Fermo E, Zanella A, Galizzi A, Valentini G (2012). "Molecular insights on pathogenic effects of mutations causing phosphoglycerate kinase deficiency". PLoS ONE 7 (2): e32065. doi:10.1371/journal.pone.0032065. PMC 3279470. PMID 22348148.
^ ^a ^b Hogg, Philip J.; Lay, Angelina J.; Jiang, Xing-Mai; Kisker, Oliver; Flynn, Evelyn; Underwood, Anne; Condron, Rosemary (14 December 2000). Nature 408 (6814): 869–873. doi:10.1038/35048596. |accessdate= requires |url= (help)
^ Danshina, Polina; GB Geyer, Q Dai, EH Goulding, WD Willis, et al (1). "Phosphoglycerate Kinase 2 (PGK2) Is Essential for Sperm Function and Male Fertility in Mice". Biology of Reproduction 82 (1): 136–145.
^ ^a ^b Dhar, A.; Samiotakis, A.; Ebbinghaus, S.; Nienhaus, L.; Homouz, D.; Gruebele, M.; Cheung, M. S. (4 October 2010). "Structure, function, and folding of phosphoglycerate kinase are strongly perturbed by macromolecular crowding". Proceedings of the National Academy of Sciences 107 (41): 17586–17591. doi:10.1073/pnas.1006760107. |accessdate= requires |url= (help)
^ Kumar S, Ma B, Tsai CJ, Wolfson H, Nussinov R (1999). "Folding funnels and conformational transitions via hinge-bending motions". Cell Biochem. Biophys. 31 (2): 141–64. doi:10.1007/BF02738169. PMID 10593256.
^ ^a ^b Yon JM, Desmadril M, Betton JM, Minard P, Ballery N, Missiakas D, Gaillard-Miran S, Perahia D, Mouawad L (1990). "Flexibility and folding of phosphoglycerate kinase". Biochimie 72 (6-7): 417–29. PMID 2124145.
^ Zerrad L, Merli A, Schröder GF, Varga A, Gráczer É, Pernot P, Round A, Vas M, Bowler MW (April 2011). "A spring-loaded release mechanism regulates domain movement and catalysis in phosphoglycerate kinase". J. Biol. Chem. 286 (16): 14040–8. doi:10.1074/jbc.M110.206813. PMC 3077604. PMID 21349853.
^ ^a ^b Varga, Andrea; Palmai, Zoltan; Gugolya, Zoltán; Gráczer, Éva; Vonderviszt, Ferenc; Závodszky, Péter; Balog, Erika; Vas, Mária (21 December 2012). "Importance of Aspartate Residues in Balancing the Flexibility and Fine-Tuning the Catalysis of Human 3-Phosphoglycerate Kinase". Biochemistry 51 (51): 10197–10207. doi:10.1021/bi301194t. |accessdate= requires |url= (help)
^ Cliff, MJ; Bowler MW, Varga A, Marston JP, et al (12). "Transition state analogue structures of human phosphoglycerate kinase establish the importance of charge balance in catalysis". J Am Chem Soc 132 (18): 6507–6516. doi:10.1021/ja100974t. PMID 20397725. Retrieved 6 March 2013.
^ Banks, R. D.; Blake, C. C. F.; Evans, P. R.; Haser, R.; Rice, D. W.; Hardy, G. W.; Merrett, M.; Phillips, A. W. (28 June 1979). "Sequence, structure and activity of phosphoglycerate kinase: a possible hinge-bending enzyme". Nature 279 (5716): 773–777. doi:10.1038/279773a0.
^ "Phosphoglycerate kinase". Mechanism, Annotation and Classification In Enzymes (MACiE). Retrieved 4 March 2013.
^ Bernstein, Bradley E; Wim G, Hol J (17). "Crystal structures of substrates and products bound to the phosphoglycerate kinase active site reveal the catalytic mechanism". Biochemistry 37 (13): 4429–4436. doi:10.1021/bi9724117. |accessdate= requires |url= (help)
^ Larsson-Raźnikiewicz M (January 1967). "Kinetic studies on the reaction catalyzed by phosphoglycerate kinase. II. The kinetic relationships between 3-phosphoglycerate, MgATP2-and activating metal ion". Biochim. Biophys. Acta 132 (1): 33–40. doi:10.1016/0005-2744(67)90189-1. PMID 6030358.
^ ^a ^b Varga, A; Chaloin K, Sagi G, Sendula R, et al (20). "Nucleotide promiscuity of 3-phosphoglycerate kinase is in focus: implications for the design of better anti-HIV analogues". Mol Biosyst 7 (6): 1863–73. doi:10.1039/c1mb05051f. PMID 21505655. |accessdate= requires |url= (help)
^ Larsson-Raźnikiewicz, Märtha; Wiksell, Eva (1 March 1978). "Inhibition of phosphoglycerate kinase by salicylates". Biochimica et Biophysica Acta (BBA) - Enzymology 523 (1): 94–100. doi:10.1016/0005-2744(78)90012-8. |accessdate= requires |url= (help)
^ Yoshida A, Tani K (1983). "Phosphoglycerate kinase abnormalities: functional, structural and genomic aspects". Biomed. Biochim. Acta 42 (11-12): S263–7. PMID 6689547.
^ ^a ^b ^c Beutler E (January 2007). "PGK deficiency". Br. J. Haematol. 136 (1): 3–11. doi:10.1111/j.1365-2141.2006.06351.x. PMID 17222195.
^ Rhodes, Melissa; Ashford, Linda; Manes, Becky; Calder, Cassie; Domm, Jennifer; Frangoul, Haydar (1 February 2011). "Bone marrow transplantation in phosphoglycerate kinase (PGK) deficiency". British Journal of Haematology 152 (4): 500–502. doi:10.1111/j.1365-2141.2010.08474.x.
^ Zieker, Derek; Königsrainer, Ingmar; Tritschler, Isabel; Löffler, Markus; Beckert, Stefan; Traub, Frank; Nieselt, Kay; Bühler, Sarah; Weller, Michael; Gaedcke, Jochen; Taichman, Russell S.; Northoff, Hinnak; Brücher BL; Königsrainer, Alfred (1). "Phosphoglycerate kinase 1 a promoting enzyme for peritoneal dissemination in gastric cancer". International Journal of Cancer: NA–NA. doi:10.1002/ijc.24835. |accessdate= requires |url= (help)
^ Hogg, Philip J.; Lay, Angelina J.; Jiang, Xing-Mai; Kisker, Oliver; Flynn, Evelyn; Underwood, Anne; Condron, Rosemary (14 December 2000). Nature 408 (6814): 869–873. doi:10.1038/35048596. |accessdate= requires |url= (help)
^ Gallois-Mantbrun, Sarah; Faraj A, Seclaman E, Sommadossi JP, et al (1). "Broad specificity of human phosphoglycerate kinase for antiviral nucleoside analogs". Biochemical Pharmacology 68 (9): 1749–1756. doi:10.1016/j.bcp.2004.06.012. PMID 15450940.

[edit] External links

-858783685 at GPnotebook
Phosphoglycerate kinase at the US National Library of Medicine Medical Subject Headings (MeSH)
Illustration at arizona.edu

Glycolysis Metabolic Pathway

Glucose	Hexokinase		Glucose 6-phosphate	Glucose-6-phosphate isomerase	Fructose 6-phosphate	phosphofructokinase-1		Fructose 1,6-bisphosphate	Fructose-bisphosphate aldolase
	ATP	ADP				ATP	ADP

Dihydroxyacetone phosphate		Glyceraldehyde 3-phosphate	Triosephosphate isomerase		Glyceraldehyde 3-phosphate	Glyceraldehyde-3-phosphate dehydrogenase			1,3-Bisphosphoglycerate
						NAD⁺ + P_i	NADH + H⁺
	+			2				2

Phosphoglycerate kinase

3-Phosphoglycerate

Phosphoglycerate mutase

2-Phosphoglycerate

Phosphopyruvate hydratase(Enolase)

Phosphoenolpyruvate

Pyruvate kinase

Pyruvate

ADP

ATP

H₂O

ADP

ATP

2

M: MET

mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m

k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon

m (A16/C10), i (k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)

Metabolism: carbohydrate metabolism: glycolysis/gluconeogenesis enzymes

Glycolysis

Hexokinase (HK1, HK2, HK3, Glucokinase)→/Glucose 6-phosphatase← · Glucose isomerase · Phosphofructokinase 1 (Liver, Muscle, Platelet)→/Fructose 1,6-bisphosphatase←

Fructose-bisphosphate aldolase (Aldolase A, B, C) · Triosephosphate isomerase

Glyceraldehyde 3-phosphate dehydrogenase · Phosphoglycerate kinase · Phosphoglycerate mutase · Enolase · Pyruvate kinase (PKLR, PKM2)

Gluconeogenesis only

to oxaloacetate: Pyruvate carboxylase · Phosphoenolpyruvate carboxykinase

from lactate (Cori cycle): Lactate dehydrogenase

from alanine (Alanine cycle): Alanine transaminase

from glycerol: Glycerol kinase · Glycerol dehydrogenase

Regulatory

Fructose 6-P,2-kinase:fructose 2,6-bisphosphatase (PFKFB1, PFKFB2, PFKFB3, PFKFB4) · Bisphosphoglycerate mutase

M: MET

mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m

k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon

m (A16/C10), i (k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)

Transferases: phosphorus-containing groups (EC 2.7)

2.7.1-2.7.4:
phosphotransferase/kinase
(PO₄)

2.7.1: OH acceptor	Hexo- Gluco- Fructo- Hepatic Galacto- Phosphofructo- 1 Liver Muscle Platelet 2 Riboflavin Shikimate Thymidine ADP-thymidine NAD⁺ Glycerol Pantothenate Mevalonate Pyruvate Deoxycytidine PFP Diacylglycerol Phosphoinositide 3 Class I PI 3 Class II PI 3 Sphingosine Glucose-1,6-bisphosphate synthase

2.7.2: COOH acceptor	Phosphoglycerate Aspartate

2.7.3: N acceptor	Creatine

2.7.4: PO₄ acceptor	Phosphomevalonate Adenylate Nucleoside-diphosphate Uridylate Guanylate Thiamine-diphosphate

2.7.6: diphosphotransferase
(P₂O₇)

2.7.7: nucleotidyltransferase
(PO₄-nucleoside)

Polymerase

DNA polymerase	DNA-directed DNA polymerase I II III IV V RNA-directed DNA polymerase Reverse transcriptase Telomerase DNA nucleotidylexotransferase/Terminal deoxynucleotidyl transferase

RNA nucleotidyltransferase	RNA polymerase/DNA-directed RNA polymerase RNA polymerase I RNA polymerase II RNA polymerase III RNA polymerase IV Primase RNA-dependent RNA polymerase PNPase

Phosphorolytic
3' to 5' exoribonuclease

Uridylyltransferase

Guanylyltransferase

mRNA capping enzyme

Other

2.7.8: miscellaneous

Phosphatidyltransferases	CDP-diacylglycerol—glycerol-3-phosphate 3-phosphatidyltransferase CDP-diacylglycerol—serine O-phosphatidyltransferase CDP-diacylglycerol—inositol 3-phosphatidyltransferase CDP-diacylglycerol—choline O-phosphatidyltransferase

Glycosyl-1-phosphotransferase	N-acetylglucosamine-1-phosphate transferase

2.7.10-2.7.13: protein kinase
(PO₄; protein acceptor)

2.7.10: protein-tyrosine	see tyrosine kinases

2.7.11: protein-serine/threonine	see serine/threonine-specific protein kinases

2.7.12: protein-dual-specificity	see serine/threonine-specific protein kinases

2.7.13: protein-histidine	Protein-histidine pros-kinase Protein-histidine tele-kinase Histidine kinase

B
enzm
1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
2.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
2.7.10
2.7.11-12
3.1
- - 3.1.3.48
- 2
- 3
- 4
  - 3.4.21
- 5
- 6
- 7
- 22
- 23
- 24
4.1
- 2
- 3
- 4
- 5
- 6
5.1
- 2
- 3
- 4
- 99
6.1-3
- 4
- 5-6

Category:EC 2.7.2 This article incorporates text from the public domain Pfam and InterPro IPR001576

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External database links

HOMSTRAD:	pgk
PANDIT:	PF00162
PROSITE:	PDOC00102
Pseudofam:	PF00162
SCOP:	3pgk
SYSTERS:	PGK

This tab holds annotation information from the InterPro database.

InterPro entry IPR001576

Phosphoglycerate kinase (EC) (PGK) is an enzyme that catalyses the formation of ATP to ADP and vice versa. In the second step of the second phase in glycolysis, 1,3-diphosphoglycerate is converted to 3-phosphoglycerate, forming one molecule of ATP. If the reverse were to occur, one molecule of ADP would be formed. This reaction is essential in most cells for the generation of ATP in aerobes, for fermentation in anaerobes and for carbon fixation in plants.

PGK is found in all living organisms and its sequence has been highly conserved throughout evolution. The enzyme exists as a monomer containing two nearly equal-sized domains that correspond to the N- and C-termini of the protein (the last 15 C-terminal residues loop back into the N-terminal domain). 3-phosphoglycerate (3-PG) binds to the N-terminal, while the nucleotide substrates, MgATP or MgADP, bind to the C-terminal domain of the enzyme. This extended two-domain structure is associated with large-scale 'hinge-bending' conformational changes, similar to those found in hexokinase [PUBMED:10593256]. At the core of each domain is a 6-stranded parallel beta-sheet surrounded by alpha helices. Domain 1 has a parallel beta-sheet of six strands with an order of 342156, while domain 2 has a parallel beta-sheet of six strands with an order of 321456. Analysis of the reversible unfolding of yeast phosphoglycerate kinase leads to the conclusion that the two lobes are capable of folding independently, consistent with the presence of intermediates on the folding pathway with a single domain folded [PUBMED:2124145].

Phosphoglycerate kinase (PGK) deficiency is associated with haemolytic anaemia and mental disorders in man [PUBMED:6689547].

This group represents a phosphoglycerate kinase.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Molecular function	phosphoglycerate kinase activity (GO:0004618)
Biological process	glycolysis (GO:0006096)

Domain organisation

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We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

	Seed (154)	Full (5701)	Representative proteomes				NCBI (4176)	Meta (4138)
	Seed (154)	Full (5701)	RP15 (516)	RP35 (944)	RP55 (1234)	RP75 (1467)	NCBI (4176)	Meta (4138)
Jalview	View	View	View	View	View	View	View	View
HTML	View		View	View	View	View
PP/heatmap	₁		View	View	View	View
Pfam viewer	View	View

¹Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: available, not generated, — not available.

Format an alignment

	Seed (154)	Full (5701)	Representative proteomes				NCBI (4176)	Meta (4138)
	Seed (154)	Full (5701)	RP15 (516)	RP35 (944)	RP55 (1234)	RP75 (1467)	NCBI (4176)	Meta (4138)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

	Seed (154)	Full (5701)	Representative proteomes				NCBI (4176)	Meta (4138)
	Seed (154)	Full (5701)	RP15 (516)	RP35 (944)	RP55 (1234)	RP75 (1467)	NCBI (4176)	Meta (4138)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download	Download
Gzipped	Download	Download	Download	Download	Download	Download	Download	Download

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation

Seed source:

Prosite

Previous IDs:

none

Type:

Domain

Author:

Sonnhammer ELL

Number in seed:

154

Number in full:

5701

Average length of the domain:

364.90 aa

Average identity of full alignment:

46 %

Average coverage of the sequence by the domain:

93.99 %

HMM information

HMM build commands:

build method: hmmbuild -o /dev/null HMM SEED

search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	19.9	19.9
Trusted cut-off	21.8	21.7
Noise cut-off	19.5	18.7

Model length:

384

Family (HMM) version:

14

Download:

download the raw HMM for this family

Species distribution

Sunburst
Tree

Sunburst controls

Show

This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

This chart is a modified "sunburst" visualisation of the species tree for this family. It shows each node in the tree as a separate arc, arranged radially with the superkingdoms at the centre and the species arrayed around the outermost ring.

How the sunburst is generated

The tree is built by considering the taxonomic lineage of each sequence that has a match to this family. For each node in the resulting tree, we draw an arc in the sunburst. The radius of the arc, its distance from the root node at the centre of the sunburst, shows the taxonomic level ("superkingdom", "kingdom", etc). The length of the arc represents either the number of sequences represented at a given level, or the number of species that are found beneath the node in the tree. The weighting scheme can be changed using the sunburst controls.

In order to reduce the complexity of the representation, we reduce the number of taxonomic levels that we show. We consider only the following eight major taxonomic levels:

superkingdom
kingdom
phylum
class
order
family
genus
species

Colouring and labels

Segments of the tree are coloured approximately according to their superkingdom. For example, archeal branches are coloured with shades of orange, eukaryotes in shades of purple, etc. The colour assignments are shown under the sunburst controls. Where space allows, the name of the taxonomic level will be written on the arc itself.

As you move your mouse across the sunburst, the current node will be highlighted. In the top section of the controls panel we show a summary of the lineage of the currently highlighed node. If you pause over an arc, a tooltip will be shown, giving the name of the taxonomic level in the title and a summary of the number of sequences and species below that node in the tree.

Anomalies in the taxonomy tree

There are some situations that the sunburst tree cannot easily handle and for which we have work-arounds in place.

Missing taxonomic levels

Some species in the taxonomic tree may not have one or more of the main eight levels that we display. For example, Bos taurus is not assigned an order in the NCBI taxonomic tree. In such cases we mark the omitted level with, for example, "No order", in both the tooltip and the lineage summary.

Unmapped species names

The tree is built by looking at each sequence in the full alignment for the family. We take the name of the species given by UniProt and try to map that to the full taxonomic tree from NCBI. In some cases, the name chosen by UniProt does not map to any node in the NCBI tree, perhaps because the chosen name is listed as a synonym or a misspelling in the NCBI taxonomy.

So that these nodes are not simply omitted from the sunburst tree, we group them together in a separate branch (or segment of the sunburst tree). Since we cannot determine the lineage for these unmapped species, we show all levels between the superkingdom and the species as "uncategorised".

Sub-species

Since we reduce the species tree to only the eight main taxonomic levels, sequences that are mapped to the sub-species level in the tree would not normally be shown. Rather than leave out these species, we map them instead to their parent species. So, for example, for sequences belonging to one of the Vibrio cholerae sub-species in the NCBI taxonomy, we show them instead as belonging to the species Vibrio cholerae.

Too many species/sequences

For large species trees, you may see blank regions in the outer layers of the sunburst. These occur when there are large numbers of arcs to be drawn in a small space. If an arc is less than approximately one pixel wide, it will not be drawn and the space will be left blank. You may still be able to get some information about the species in that region by moving your mouse across the area, but since each arc will be very small, it will be difficult to accurately locate a particular species.

Loading sunburst data...

Tree controls

Hide

The tree shows the occurrence of this domain across different species. More...

Species trees

We show the species tree in one of two ways. For smaller trees we try to show an interactive representation, which allows you to select specific nodes in the tree and view them as an alignment or as a set of Pfam domain graphics.

Unfortunately we have found that there are problems viewing the interactive tree when the it becomes larger than a certain limit. Furthermore, we have found that Internet Explorer can become unresponsive when viewing some trees, regardless of their size. We therefore show a text representation of the species tree when the size is above a certain limit or if you are using Internet Explorer to view the site.

If you are using IE you can still load the interactive tree by clicking the "Generate interactive tree" button, but please be aware of the potential problems that the interactive species tree can cause.

Interactive tree

For all of the domain matches in a full alignment, we count the number that are found on all sequences in the alignment. This total is shown in the purple box.

We also count the number of unique sequences on which each domain is found, which is shown in green. Note that a domain may appear multiple times on the same sequence, leading to the difference between these two numbers.

Finally, we group sequences from the same organism according to the NCBI code that is assigned by UniProt, allowing us to count the number of distinct sequences on which the domain is found. This value is shown in the pink boxes.

We use the NCBI species tree to group organisms according to their taxonomy and this forms the structure of the displayed tree. Note that in some cases the trees are too large (have too many nodes) to allow us to build an interactive tree, but in most cases you can still view the tree in a plain text, non-interactive representation. Those species which are represented in the seed alignment for this domain are highlighted.

You can use the tree controls to manipulate how the interactive tree is displayed:

show/hide the summary boxes
highlight species that are represented in the seed alignment
expand/collapse the tree or expand it to a given depth
select a sub-tree or a set of species within the tree and view them graphically or as an alignment
save a plain text representation of the tree

Loading...

Please note: for large trees this can take some time. While the tree is loading, you can safely switch away from this tab but if you browse away from the family page entirely, the tree will not be loaded.

Interactions

There is 1 interaction for this family. More...

PGK

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the PGK domain has been found. There are 60 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

Loading structure mapping...

Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

Family: PGK (PF00162)

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Summary: Phosphoglycerate kinase

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Phosphoglycerate kinase Edit Wikipedia article

Contents

[edit] Biological function

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[edit] Overview

[edit] Role of magnesium

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Phosphoglycerate kinase Provide feedback

External database links

InterPro entry IPR001576

Gene Ontology

Domain organisation

Alignments

Alignment types

Viewing

Reformatting

Downloading

View options

Format an alignment

Download options

External links

HMM logo

Trees

Curation and family details

Curation

HMM information

Species distribution

Sunburst controls

Weight segments by...

Change the size of the sunburst

Colour assignments

Selections

Currently selected:

How the sunburst is generated

Colouring and labels

Anomalies in the taxonomy tree

Missing taxonomic levels

Unmapped species names

Sub-species

Too many species/sequences

Tree controls

Annotation

Download tree

Selected sequences

Species trees

Interactive tree

Interactions

Structures