Summary: 6-phosphofructo-2-kinase

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This is the Wikipedia entry entitled "6-phosphofructo-2-kinase". More...

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6-phosphofructo-2-kinase Edit Wikipedia article

6-phosphofructo-2-kinase

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Databases

PDB structures

AmiGO / EGO

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PMC	articles
PubMed	articles

6PF2K

crystal structure of human liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase

Identifiers

Symbol

6PF2K

Pfam clan

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

In enzymology, a 6-phosphofructo-2-kinase (EC 2.7.1.105) is an enzyme that catalyzes the chemical reaction

ATP + beta-D-fructose 6-phosphate $\rightleftharpoons$ ADP + beta-D-fructose 2,6-bisphosphate

Thus, the two substrates of this enzyme are ATP and beta-D-fructose 6-phosphate, whereas its two products are ADP and beta-D-fructose 2,6-bisphosphate.

This enzyme belongs to the family of transferases, specifically those transferring phosphorus-containing groups (phosphotransferases) with an alcohol group as acceptor. The systematic name of this enzyme class is ATP:beta-D-fructose-6-phosphate 2-phosphotransferase. Other names in common use include phosphofructokinase 2, 6-phosphofructose 2-kinase, 6-phosphofructo-2-kinase (phosphorylating), fructose 6-phosphate 2-kinase, and ATP:D-fructose-6-phosphate 2-phosphotransferase. This enzyme participates in fructose and mannose metabolism. The enzyme is important in the regulation of hepatic carbohydrate metabolism and is found in greatest quantities in the liver, kidney and heart. In mammals, several genes often encode different isoforms, each of which differs in its tissue distribution and enzymatic activity.^[1] The family described here bears a resemblance to the ATP-driven phospho-fructokinases, however, they share little sequence similarity, although a few residues seem key to their interaction with fructose 6-phosphate.^[2]

[edit] Structural studies

As of late 2007, 8 structures have been solved for this class of enzymes, with PDB accession codes 1BIF, 1K6M, 2AXN, 2BIF, 2DWO, 2DWP, 2I1V, and 3BIF.

[edit] References

^ Heine-SuÃ±er D, DÃaz-GuillÃ©n MA, Lange AJ, RodrÃguez de CÃ³rdoba S (May 1998). "Sequence and structure of the human 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase heart isoform gene (PFKFB2)". Eur. J. Biochem. 254 (1): 10310. doi:10.1046/j.1432-1327.1998.2540103.x. PMID 9652401.
^ Wang X, Deng Z, Kemp RG (September 1998). "An essential methionine residue involved in substrate binding by phosphofructokinases". Biochem. Biophys. Res. Commun. 250 (2): 4668. doi:10.1006/bbrc.1998.9311. PMID 9753654.

Van Schaftingen E, Hers HG (1981). "Phosphofructokinase 2: the enzyme that forms fructose 2,6-bisphosphate from fructose 6-phosphate and ATP". Biochem. Biophys. Res. Commun. 101 (3): 107884. doi:10.1016/0006-291X(81)91859-3. PMID 6458291.

This article incorporates text from the public domain Pfam and InterPro IPR013079

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This is the Wikipedia entry entitled "Phosphofructokinase 2". More...

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Phosphofructokinase 2 Edit Wikipedia article

6-phosphofructo-2-kinase

Identifiers

Databases

PDB structures

AmiGO / EGO

Search
PMC	articles
PubMed	articles
NCBI	proteins

fructose-2,6-bisphosphate 2-phosphatase

Identifiers

Databases

PDB structures

AmiGO / EGO

Search
PMC	articles
PubMed	articles
NCBI	proteins

6-phosphofructo-2-kinase

Structure of PFK2. Shown: kinase domain (cyan) and the phosphatase domain (green).

Identifiers

Symbol

6PF2K

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

Phosphofructokinase 2 (PFK2) or fructose bisphosphatase 2 (FBPase2), is an enzyme responsible for regulating the rates of glycolysis and gluconeogenesis in the human body. It is a homodimer of 55 kDa subunits arranged in a head-to-head fashion, with each polypeptide chain consisting of independent kinase and phosphatase domain. When Ser-32 of the bifunctional protein is phosphorylated, the negative charge causes the conformation change of the enzyme to favor the FBPase2 activity; otherwise, PFK2 activity is favored.^[1] PFK2 domain is closely related to the superfamily of mononucleotide binding proteins including adenylate cyclase, whereas that of FBPase2 is related to a family of proteins that include phosphoglycerate mutases.

[edit] Structure

The monomers of the bifunctional protein are clearly divided into two functional domains. The kinase domain is located on the N-terminal.^[2] It consists of a central six-stranded Î² sheet, with five parallel strands and an antiparallel edge strand, surrounded by seven Î± helices.^[3] The domain contains nucleotide-binding fold (nbf) at the C-terminal end of the first Î²-strand,^[4] and thus resembles the structure of adenylate kinase.

On the other hand, the phosphatase domain is located on the C-terminal.^[5] It resembles the family of proteins that include phosphoglycerate mutases (PGMs) and acid phosphatases.^[6] The domain has a mixed Î±/ Î² structure, with a six-stranded central Î² sheet, plus an additional Î±-helical subdomain that covers the presumed active site of the molecule.^[3] Finally, N-terminal region modulates PFK2 and FBPase2 activities, and stabilizes the dimer form of the enzyme.^[6]^[7]

[edit] Function

When glucose level is low, glucagon is released into the bloodstream, triggering a cAMP signal cascade. In the liver Protein kinase A inactivates the PFK-2 domain of the bifunctional enzyme via phosphorylation, however this does not occur in skeletal muscle. The F-2,6-BPase domain is then activated which lowers fructose 2,6-bisphosphate (F-2,6-BP) levels. Because F-2,6-BP normally stimulates phosphofructokinase-1(PFK1), the decrease in its concentration leads to the inhibition of glycolysis and the stimulation of gluconeogenesis.^[8]

On the other hand, when the glucose level increases, the level of fructose 6-phosphate (F6P) subsequently rises and the molecule stimulates phosphoprotein phosphatase-1, which removes phosphoryl group from the bifunctional protein. So PFK2 domain is activated and the kinase catalyzes the formation of F-2,6-BP. Thus, glycolysis is stimulated and gluconeogenesis is inhibited.

[edit] Regulation

The allosteric regulation of PFK2 is very similar to the regulation of PFK1.^[9] High levels of AMP or phosphate group signifies low levels of glucose and thus stimulates PFK2. On the other hand, a high concentration of phosphoenolpyruvate(PEP) and citrate signifies that there is a high level of biosynthetic precursor and hence inhibits PFK2. However, unlike PFK1, PFK2 is not affected by the ATP concentration.

Glucagon inhibits PFK2 by activating Protein Kinase A, causing the FBPase activity to be favored, decreasing [F-2,6-BP], and thereby inhibiting glycolysis through the inhibition of PFK1. Insulin activates PFK2 by activating Protein Phosphatase, increasing [F-2,6-BP].

[edit] Reaction mechanism

PFK2 is likely to catalyze the "simple" transfer of Î³-phosphoryl group of ATP onto the hydroxyl present on C-2 of fructose-6-phosphate. Yet, the formation of fructose 2,6-bisphosphate could theoretically occur by a variety of mechanisms, including the intermediary formation of Fructose-6-phosphate 2-pyrophosphate.^[9]

The hydrolysis of fructose 2,6-biphosphate is likely to follow the below steps:^[10]

Histidine acts as a nucleophile and attacks the 2-phosphate of F-2,6-BP
The stabilization of pentacoordinated transition state by several salt bridges and hydrogen bonding.
The breakdown of the transition state and the release of F6P.
Histidine increases the nucleophilicity of water, which attacks phosphohistidine, generating phosphate and newly protonated histidine.

[edit] Clinical significance

The Pfkfb2 gene encoding PFK2/FBPase2 protein is linked to the predisposition to schizophrenia.^[11] Furthermore, the control of PFK2/FBPase2 activity was found to be linked to heart functioning and the control against hypoxia.^[12]

[edit] Isozymes

Five mammalian isozymes of the protein have been reported to date, difference rising by either the transcription of different enzymes or alternative splicing.^[13]^[14]^[15]The isozymes differ radically in their regulation and the discussions above are based on liver isozyme.^[3]

Humans genes encoding proteins possessing phosphofructokinase 2 activity include:

PFKFB1, PFKFB2, PFKFB3, PFKFB4

[edit] References

^ Kurland IJ, el-Maghrabi MR, Correia JJ, Pilkis SJ (March 1992). "Rat liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase. Properties of phospho- and dephospho- forms and of two mutants in which Ser32 has been changed by site-directed mutagenesis". J. Biol. Chem. 267 (7): 4416â23. PMID 1339450.
^ Kurland I, Chapman B, Lee YH, Pilkis S (August 1995). "Evolutionary reengineering of the phosphofructokinase active site: ARG-104 does not stabilize the transition state in 6-phosphofructo-2-kinase". Biochem. Biophys. Res. Commun. 213 (2): 663â72. doi:10.1006/bbrc.1995.2183. PMID 7646523.
^ ^a ^b ^c Hasemann CA, Istvan ES, Uyeda K, Deisenhofer J (September 1996). "The crystal structure of the bifunctional enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase reveals distinct domain homologies". Structure 4 (9): 1017â29. doi:10.1016/S0969-2126(96)00109-8. PMID 8805587.
^ Walker JE, Saraste M, Runswick MJ, Gay NJ (1982). "Distantly related sequences in the alpha- and beta-subunits of ATP synthase, myosin, kinases and other ATP-requiring enzymes and a common nucleotide binding fold". EMBO J. 1 (8): 945â51. PMC 553140. PMID 6329717. //www.ncbi.nlm.nih.gov/pmc/articles/PMC553140/.
^ Li L, Lin K, Pilkis J, Correia JJ, Pilkis SJ (October 1992). "Hepatic 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase. The role of surface loop basic residues in substrate binding to the fructose-2,6-bisphosphatase domain". J. Biol. Chem. 267 (30): 21588â94. PMID 1328239.
^ ^a ^b Stryer, Lubert; Berg, Jeremy Mark; Tymoczko, John L. (2008). "The Balance Between Glycolysis and Gluconeogenesis in the Liver Is Sensitive to Blood-Glucose Concentration". Biochemistry (Looseleaf). San Francisco: W. H. Freeman. pp. 466â467. ISBN 1-4292-3502-0.
^ Tominaga N, Minami Y, Sakakibara R, Uyeda K (July 1993). "Significance of the amino terminus of rat testis fructose-6-phosphate, 2-kinase:fructose-2,6-bisphosphatase". J. Biol. Chem. 268 (21): 15951â7. PMID 8393455.
^ Pilkis SJ, Claus TH, Kurland IJ, Lange AJ (1995). "6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase: a metabolic signaling enzyme". Annu. Rev. Biochem. 64: 799â835. doi:10.1146/annurev.bi.64.070195.004055. PMID 7574501.
^ ^a ^b Van Schaftingen E, Hers HG (August 1981). "Phosphofructokinase 2: the enzyme that forms fructose 2,6-bisphosphate from fructose 6-phosphate and ATP". Biochem. Biophys. Res. Commun. 101 (3): 1078â84. doi:10.1016/0006-291X(81)91859-3. PMID 6458291.
^ Lin K, Li L, Correia JJ, Pilkis SJ (April 1992). "Glu327 is part of a catalytic triad in rat liver fructose-2,6-bisphosphatase". J. Biol. Chem. 267 (10): 6556â62. PMID 1313012.
^ Stone WS, Faraone SV, Su J, Tarbox SI, Van Eerdewegh P, Tsuang MT (May 2004). "Evidence for linkage between regulatory enzymes in glycolysis and schizophrenia in a multiplex sample". Am. J. Med. Genet. B Neuropsychiatr. Genet. 127B (1): 5â10. doi:10.1002/ajmg.b.20132. PMID 15108172.
^ Wang Q, Donthi RV, Wang J, Lange AJ, Watson LJ, Jones SP, Epstein PN (June 2008). "Cardiac phosphatase-deficient 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase increases glycolysis, hypertrophy, and myocyte resistance to hypoxia". Am. J. Physiol. Heart Circ. Physiol. 294 (6): H2889â97. doi:10.1152/ajpheart.91501.2007. PMID 18456722.
^ Darville MI, Crepin KM, Hue L, Rousseau GG (September 1989). "5' flanking sequence and structure of a gene encoding rat 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase". Proc. Natl. Acad. Sci. U.S.A. 86 (17): 6543â7. doi:10.1073/pnas.86.17.6543. PMC 297880. PMID 2549541. //www.ncbi.nlm.nih.gov/pmc/articles/PMC297880/.
^ Tsuchiya Y, Uyeda K (May 1994). "Bovine heart fructose 6-P,2-kinase:fructose 2,6-bisphosphatase mRNA and gene structure". Arch. Biochem. Biophys. 310 (2): 467â74. doi:10.1006/abbi.1994.1194. PMID 8179334.
^ Sakata J, Abe Y, Uyeda K (August 1991). "Molecular cloning of the DNA and expression and characterization of rat testes fructose-6-phosphate,2-kinase:fructose-2,6-bisphosphatase". J. Biol. Chem. 266 (24): 15764â70. PMID 1651918.

[edit] Further reading

Rider MH, Bertrand L, Vertommen D, Michels PA, Rousseau GG, Hue L (August 2004). "6-Phosphofructo-2-kinase/fructose-2,6-bisphosphatase: head-to-head with a bifunctional enzyme that controls glycolysis". Biochem. J. 381 (Pt 3): 561â79. doi:10.1042/BJ20040752. PMC 1133864. PMID 15170386. //www.ncbi.nlm.nih.gov/pmc/articles/PMC1133864/.

[edit] External links

Fructose 2,6-bisphosphatase at the US National Library of Medicine Medical Subject Headings (MeSH)
6-phosphofructokinase of Arabidopsis thaliana at genome.jp

Hydrolase: esterases (EC 3.1)

3.1.1: Carboxylic ester hydrolases

Lipase

Phospholipase
- A1
- A2
- B

3.1.2: Thioesterase

3.1.3: Phosphatase

Alkaline phosphatase
- ALPI
- ALPL
- ALPP
Acid phosphatase (Prostatic)/Tartrate-resistant acid phosphatase/Purple acid phosphatases
Nucleotidase
Glucose 6-phosphatase
Fructose 1,6-bisphosphatase
- Calcineurin
Phosphoprotein phosphatase
- PP2A
OCRL
Pyruvate dehydrogenase phosphatase
Fructose 6-P,2-kinase:fructose 2,6-bisphosphatase
PTEN
Phytase
Inositol-phosphate phosphatase
- IMPA1

3.1.4: Phosphodiesterase

3.1.6: Sulfatase

Nuclease (includes
deoxyribonuclease and
ribonuclease)

3.1.11-16: Exonuclease

Exodeoxyribonuclease	RecBCD

Exoribonuclease	Oligonucleotidase

3.1.21-31: Endonuclease

Endodeoxyribonuclease	Deoxyribonuclease I Deoxyribonuclease II Deoxyribonuclease IV Restriction enzyme UvrABC endonuclease

Endoribonuclease	RNase III RNase H 1 2A 2B 2C RNase P RNase A 1 2 3 4/5 RNase T1 RNA-induced silencing complex

either deoxy- or ribo-	Aspergillus nuclease S1 Micrococcal nuclease

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

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-diacylglycerolâglycerol-3-phosphate 3-phosphatidyltransferase CDP-diacylglycerolâserine O-phosphatidyltransferase CDP-diacylglycerolâinositol 3-phosphatidyltransferase CDP-diacylglycerolâcholine 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

Metabolism: carbohydrate metabolism: glycolysis/gluconeogenesis enzymes

Glycolysis

Hexokinase (HK1, HK2, HK3, Glucokinase)â/Glucose 6-phosphataseâ Â· Glucose isomerase Â· Phosphofructokinase 1 (Liver, Muscle, Platelet)â/Fructose 1,6-bisphosphataseâ

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

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

Gluconeogenesis only

to oxaloacetate: Pyruvate carboxylase Â· Phosphoenolpyruvate carboxykinase

from lactate (Cori cycle): Lactate dehydrogenase

from alanine (Alanine cycle): Alanine transaminase

from glycerol: Glycerol kinase Â· Glycerol dehydrogenase

Regulatory

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

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

6-phosphofructo-2-kinase Provide feedback

This enzyme occurs as a bifunctional enzyme with fructose-2,6-bisphosphatase. The bifunctional enzyme catalyses both the synthesis and degradation of fructose-2,6-bisphosphate, a potent regulator of glycolysis [1]. This enzyme contains a P-loop motif.

Literature references

Hasemann CA, Istvan ES, Uyeda K, Deisenhofer J; , Structure 1996;4:1017-1029.: The crystal structure of the bifunctional enzyme 6-phosphofructo-2- kinase/fructose-2,6-bisphosphatase reveals distinct domain homologies. PUBMED:8805587 EPMC:8805587

External database links

PANDIT:	PF01591
PROSITE:	PDOC00158
Pseudofam:	PF01591
SCOP:	1bif
SYSTERS:	6PF2K

This tab holds annotation information from the InterPro database.

InterPro entry IPR013079

6-Phosphofructo-2-kinase (EC, EC) is a bifunctional enzyme that catalyses both the synthesis and the degradation of fructose-2, 6-bisphosphate. The fructose-2,6-bisphosphatase reaction involves a phosphohistidine intermediate. The catalytic pathway is: ATP + D-fructose 6-phosphate = ADP + D-fructose 2,6-bisphosphate D-fructose 2,6-bisphosphate + H₂O = 6-fructose 6-phosphate + P_i The enzyme is important in the regulation of hepatic carbohydrate metabolism and is found in greatest quantities in the liver, kidney and heart. In mammals, several genes often encode different isoforms, each of which differs in its tissue distribution and enzymatic activity [PUBMED:9652401]. The family described here bears a resemblance to the ATP-driven phospho-fructokinases, however, they share little sequence similarity, although a few residues seem key to their interaction with fructose 6-phosphate [PUBMED:9753654].

This domain forms the N-terminal region of this enzyme, while INTERPRO forms the C-terminal domain.

Gene Ontology

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

Molecular function	ATP binding (GO:0005524)
Molecular function	6-phosphofructo-2-kinase activity (GO:0003873)
Biological process	fructose metabolic process (GO:0006000)

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Pfam Clan

This family is a member of clan P-loop_NTPase (CL0023), which contains the following 198 members:

6PF2K AAA AAA-ATPase_like AAA_10 AAA_11 AAA_12 AAA_13 AAA_14 AAA_15 AAA_16 AAA_17 AAA_18 AAA_19 AAA_2 AAA_21 AAA_22 AAA_23 AAA_24 AAA_25 AAA_26 AAA_27 AAA_28 AAA_29 AAA_3 AAA_30 AAA_31 AAA_32 AAA_33 AAA_34 AAA_35 AAA_4 AAA_5 AAA_6 AAA_7 AAA_8 AAA_9 AAA_PrkA ABC_ATPase ABC_tran ABC_tran_2 Adeno_IVa2 Adenylsucc_synt ADK AFG1_ATPase AIG1 APS_kinase Arch_ATPase Arf ArgK ArsA_ATPase ATP-synt_ab ATP_bind_1 ATP_bind_2 Bac_DnaA CbiA CMS1 CoaE CobA_CobO_BtuR CobU cobW CPT CTP_synth_N Cytidylate_kin Cytidylate_kin2 DAP3 DEAD DEAD_2 DLIC DNA_pack_C DNA_pack_N DNA_pol3_delta DNA_pol3_delta2 DnaB_C dNK DUF1253 DUF1611 DUF2075 DUF2478 DUF258 DUF2791 DUF2813 DUF3584 DUF463 DUF815 DUF853 DUF87 DUF927 Dynamin_N Exonuc_V_gamma FeoB_N Fer4_NifH Flavi_DEAD FTHFS FtsK_SpoIIIE G-alpha Gal-3-0_sulfotr GBP GTP_EFTU GTP_EFTU_D2 GTP_EFTU_D4 Gtr1_RagA Guanylate_kin GvpD HDA2-3 Helicase_C Helicase_C_2 Helicase_C_4 Helicase_RecD Herpes_Helicase Herpes_ori_bp Herpes_TK IIGP IPPT IPT IstB_IS21 KaiC KAP_NTPase Kinesin Kinesin-relat_1 Kinesin-related KTI12 LpxK MCM MEDS Mg_chelatase Mg_chelatase_2 MipZ Miro MMR_HSR1 MobB MukB MutS_V Myosin_head NACHT NB-ARC NOG1 NTPase_1 ParA Parvo_NS1 PAXNEB PduV-EutP PhoH PIF1 Podovirus_Gp16 Polyoma_lg_T_C Pox_A32 PPK2 PPV_E1_C PRK Rad17 Rad51 Ras RecA ResIII RHD3 RHSP RNA12 RNA_helicase RuvB_N SbcCD_C SecA_DEAD Septin Sigma54_activ_2 Sigma54_activat SKI SMC_N SNF2_N Spore_IV_A SRP54 SRPRB Sulfotransfer_1 Sulfotransfer_2 Sulfotransfer_3 Sulphotransf T2SE T4SS-DNA_transf Terminase_1 Terminase_3 Terminase_6 Terminase_GpA Thymidylate_kin TIP49 TK TniB Torsin TraG-D_C tRNA_lig_kinase TrwB_AAD_bind UPF0079 UvrD-helicase UvrD_C UvrD_C_2 Viral_helicase1 VirC1 VirE YhjQ Zeta_toxin Zot

Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

There are various ways to view or download the sequence alignments that we store. We provide several sequence viewers and a plain-text Stockholm-format file for download.

Alignment types

We make a range of alignments for each Pfam-A family:

seed: the curated alignment from which the HMM for the family is built
full: the alignment generated by searching the sequence database using the HMM
RP15/RP35/RP55/RP75: Representative Proteomes (RPs) at 15%, 35%, 55% and 75% co-membership thresholds
NCBI: alignment generated by searching the NCBI sequence database using the family HMM
meta: alignment generated by searching the metagenomics sequence database using the family HMM

Viewing

You can see the alignments as HTML or in three different sequence viewers:

jalview: a Java applet developed at the University of Dundee. You will need Java installed before running jalview
HTML: an HTML page showing the whole alignment.Please note: full Pfam alignments can be very large. These HTML views are extremely large and often cause problems for browsers. Please use either jalview or the Pfam viewer if you have trouble viewing the HTML version
PP/Heatmap: an HTML-based representation of the alignment, coloured according to the posterior-probability (PP) values from the HMM. As for the standard HTML view, heatmap alignments can also be very large and slow to render.
Pfam viewer: an HTML-based viewer that uses DAS to retrieve alignment fragments on request

Reformatting

You can download (or view in your browser) a text representation of a Pfam alignment in various formats:

Selex
Stockholm
FASTA
MSF

You can also change the order in which sequences are listed in the alignment, change how insertions are represented, alter the characters that are used to represent gaps in sequences and, finally, choose whether to download the alignment or to view it in your browser directly.

Downloading

You may find that large alignments cause problems for the viewers and the reformatting tool, so we also provide all alignments in Stockholm format. You can download either the plain text alignment, or a gzipped version of it.

View options

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 (11)	Full (1160)	Representative proteomes				NCBI (1195)	Meta (96)
	Seed (11)	Full (1160)	RP15 (187)	RP35 (351)	RP55 (557)	RP75 (696)	NCBI (1195)	Meta (96)
Jalview	View	View	View	View	View	View	View	View
HTML	View	View	View	View	View	View
PP/heatmap	₁	View	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 (11)	Full (1160)	Representative proteomes				NCBI (1195)	Meta (96)
	Seed (11)	Full (1160)	RP15 (187)	RP35 (351)	RP55 (557)	RP75 (696)	NCBI (1195)	Meta (96)
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 (11)	Full (1160)	Representative proteomes				NCBI (1195)	Meta (96)
	Seed (11)	Full (1160)	RP15 (187)	RP35 (351)	RP55 (557)	RP75 (696)	NCBI (1195)	Meta (96)
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:

Pfam-B_717 (release 4.1)

Previous IDs:

none

Type:

Domain

Author:

Bateman A

Number in seed:

11

Number in full:

1160

Average length of the domain:

194.90 aa

Average identity of full alignment:

37 %

Average coverage of the sequence by the domain:

39.97 %

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	20.8	20.8
Trusted cut-off	20.8	20.8
Noise cut-off	20.7	20.7

Model length:

223

Family (HMM) version:

13

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 are 2 interactions for this family. More...

6PF2K His_Phos_1

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 6PF2K domain has been found. There are 13 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: 6PF2K (PF01591)

Jump to...

Summary: 6-phosphofructo-2-kinase

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Editing Wikipedia articles

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6-phosphofructo-2-kinase Edit Wikipedia article

[edit] Structural studies

[edit] References

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Phosphofructokinase 2 Edit Wikipedia article

Contents

[edit] Structure

[edit] Function

[edit] Regulation

[edit] Reaction mechanism

[edit] Clinical significance

[edit] Isozymes

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6-phosphofructo-2-kinase Provide feedback

Literature references

External database links

InterPro entry IPR013079

Gene Ontology

Domain organisation

Pfam Clan

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