Summary: Hexokinase

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Wikipedia: Hexokinase
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Hexokinase Edit Wikipedia article

Hexokinase

Crystal structures of hexokinase 1 from Kluyveromyces lactis.^[1]

Identifiers

Databases

PDB structures

AmiGO / EGO

Search
PMC	articles
PubMed	articles
NCBI	proteins

hexokinase 1
Identifiers
Symbol	HK1
Entrez	3098
HUGO	4922
OMIM	142600
RefSeq	NM_000188
UniProt	P19367
Other data
Locus	Chr. 10 q22

hexokinase 2
Identifiers
Symbol	HK2
Entrez	3099
HUGO	4923
OMIM	601125
RefSeq	NM_000189
UniProt	P52789
Other data
Locus	Chr. 2 p13

hexokinase 3 (white cell)
Identifiers
Symbol	HK3
Entrez	3101
HUGO	4925
OMIM	142570
RefSeq	NM_002115
UniProt	P52790
Other data
Locus	Chr. 5 q35.2

Hexokinase_1

crystal structure of human glucokinase

Identifiers

Symbol

Hexokinase_1

Pfam clan

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

Hexokinase_2

rat brain hexokinase type i complex with glucose and inhibitor glucose-6-phosphate

Identifiers

Symbol

Hexokinase_2

Pfam clan

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

A hexokinase is an enzyme that phosphorylates hexoses (six-carbon sugars), forming hexose phosphate. In most organisms, glucose is the most important substrate of hexokinases, and glucose-6-phosphate is the most important product. Scientists have discovered and demonstrated that Hexokinase possesses the ability to transfer an inorganic phosphate group from ATP to a substrate.

Hexokinases should not be confused with glucokinase, which is a specific isoform of hexokinase. While other hexokinases are capable of phosphorylating several hexoses, glucokinase acts with a 50-fold lower substrate affinity and its only hexose substrate is glucose.

Variation

Genes that encode hexokinase have been discovered in every domain of life, and exist among a variety of species that range from bacteria, yeast, and plants to humans and other vertebrates. They are categorized as actin fold proteins, sharing a common ATP binding site core that is surrounded by more variable sequences which determine substrate affinities and other properties.

Several hexokinase isoforms or isozymes that provide different functions can occur in a single species.

Reaction

The intracellular reactions mediated by hexokinases can be typified as:

Hexose-CH₂OH + MgATP2−
→ Hexose-CH₂O-PO2−
3 + MgADP−
+ H⁺

where hexose-CH₂OH represents any of several hexoses (like glucose) that contain an accessible -CH₂OH moiety.

Consequences of hexose phosphorylation

Phosphorylation of a hexose such as glucose often limits it to a number of intracellular metabolic processes, such as glycolysis or glycogen synthesis. This is because phosphorylated hexoses are charged, and thus more difficult to transport out of a cell.

In patients with essential fructosuria, metabolism of fructose by hexokinase to fructose-6-phosphate is the primary method of metabolizing dietary fructose; this pathway is not significant in normal individuals.

Size of different isoforms

Most bacterial hexokinases are approximately 50 kD in size. Multicellular organisms including plants and animals often have more than one hexokinase isoform. Most are about 100 kD in size and consist of two halves (N and C terminal), which share much sequence homology. This suggests an evolutionary origin by duplication and fusion of a 50kD ancestral hexokinase similar to those of bacteria.

Types of mammalian hexokinase

There are four important mammalian hexokinase isozymes (EC 2.7.1.1) that vary in subcellular locations and kinetics with respect to different substrates and conditions, and physiological function. They are designated hexokinases I, II, III, and IV or hexokinases A, B, C, and D.

Hexokinases I, II, and III

Hexokinases I, II, and III are referred to as "low-K_m" isozymes because of a high affinity for glucose (below 1 mM). Hexokinases I and II follow Michaelis-Menten kinetics at physiologic concentrations of substrates.^{[citation needed]} All three are strongly inhibited by their product, glucose-6-phosphate. Molecular weights are around 100 kD. Each consists of two similar 50kD halves, but only in hexokinase II do both halves have functional active sites.

Hexokinase I/A is found in all mammalian tissues, and is considered a "housekeeping enzyme," unaffected by most physiological, hormonal, and metabolic changes.
Hexokinase II/B constitutes the principal regulated isoform in many cell types and is increased in many cancers. It is the hexokinase found in muscle and heart. Hexokinase II is also located at the mitochondria outer membrane so it can have direct access to ATP.^[2]
Hexokinase III/C is substrate-inhibited by glucose at physiologic concentrations. Little is known about the regulatory characteristics of this isoform.

Hexokinase IV ("glucokinase")

Mammalian hexokinase IV, also referred to as glucokinase, differs from other hexokinases in kinetics and functions.

The location of the phosphorylation on a subcellular level occurs when glucokinase translocates between the cytoplasm and nucleus of liver cells. Glucokinase can only phosphorylate glucose if the concentration of this substrate is high enough; its Km for glucose is 100 times higher than that of hexokinases I, II, and III.

Hexokinase IV is monomeric, about 50kD, displays positive cooperativity with glucose, and is not allosterically inhibited by its product, glucose-6-phosphate.

Hexokinase IV is present in the liver, pancreas, hypothalamus, small intestine, and perhaps certain other neuroendocrine cells, and plays an important regulatory role in carbohydrate metabolism. In the beta cells of the pancreatic islets, it serves as a glucose sensor to control insulin release, and similarly controls glucagon release in the alpha cells. In hepatocytes of the liver, glucokinase responds to changes of ambient glucose levels by increasing or reducing glycogen synthesis.

Hexokinase in glycolysis

Glucose is unique in that it can be used to produce ATP by all cells in both the presence and absence of molecular oxygen (O₂). The first step in glycolysis is the phosphorylation of glucose by hexokinase.

D-Glucose	Hexokinase		α-D-Glucose-6-phosphate

	ATP	ADP

Compound C00031 at KEGG Pathway Database. Enzyme 2.7.1.1 at KEGG Pathway Database. Compound C00668 at KEGG Pathway Database. Reaction R01786 at KEGG Pathway Database.

By catalyzing the phosphorylation of glucose to yield glucose 6-phosphate, hexokinases maintain the downhill concentration gradient that favors the facilitated transport of glucose into cells. This reaction also initiates all physiologically relevant pathways of glucose utilization, including glycolysis and the pentose phosphate pathway.^[3] The addition of a charged phosphate group at the 6-position of hexoses also ensures 'trapping' of glucose and 2-deoxyhexose glucose analogs (e.g. 2-deoxyglucose, and 2-fluoro-2-deoxyglucose) within cells, as charged hexose phosphates cannot easily cross the cell membrane.

Association with mitochondria

Hexokinases I and II can associate physically to the outer surface of the external membrane of mitochondria through specific binding to a porin, or voltage dependent anion channel. This association confers hexokinase direct access to ATP generated by mitochondria, which is one of the two substrates of hexokinase. Mitochondrial hexokinase is highly elevated in rapidly growing malignant tumor cells, with levels up to 200 times higher than normal tissues. Mitochondrially bound hexokinase has been demonstrated to be the driving force^[4] for the extremely high glycolytic rates that take place aerobically in tumor cells (the so-called Warburg effect described by Otto Heinrich Warburg in 1930).

Hydropathy plot

Hydropathy plot of hexokinase

The potential transmembrane portions of a protein can be detected by hydropathy analysis. A hydropathy analysis uses an algorithm that quantifies the hydrophobic character at each position along the polypeptide chain. One of the accepted hydropathy scales is that of Kyte and Doolittle which relies on the generation of hydropathy plots. In these plots, the negative numbers represent hydrophilic regions and the positive numbers represent hydrophobic regions on the y-axis. A potential transmembrane domain is about 20 amino acids long on the x-axis.

A hydropathy analysis of hexokinase in yeast has been created by these standards. It appears as if hexokinase possesses a single potential transmembrane domain located around amino acid 400. Therefore, hexokinase is most likely not an integral membrane protein in yeast.^[5]

References

^ PDB: 3O08; Kuettner EB, Kettner K, Keim A, Svergun DI, Volke D (2010). "Crystal structure of dimeric KlHxk1 in crystal form I". doi:10.2210/pdb3o08/pdb.
^ "Hexokinase data on Uniprot". uniprot.org.
^ Robey, RB; Hay, N (2006). "Mitochondrial hexokinases, novel mediators of the antiapoptotic effects of growth factors and Akt". Oncogene. 25 (34): 4683–96. doi:10.1038/sj.onc.1209595. PMID 16892082.
^ Bustamante E, Pedersen P (1977). "High aerobic glycolysis of rat hepatoma cells in culture: role of mitochondrial hexokinase". Proc Natl Acad Sci USA. 74 (9): 3735–9. Bibcode:1977PNAS...74.3735B. doi:10.1073/pnas.74.9.3735. PMC 431708. PMID 198801.
^ Bowen, R. A. Molecular Toolkit: Protein Hydrophobicity Plots. Colorado State University, 1998. Web. 15 Nov. 2010. <http://www.vivo.colostate.edu/molkit/index.html>

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

Metabolism: carbohydrate metabolism: glycolysis/gluconeogenesis enzymes

Glycolysis

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

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 kinase

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

Nucleotidyltransferase

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

v t e Enzymes

Activity	Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Catalytically perfect enzyme Coenzyme Cofactor Enzyme catalysis

Regulation	Allosteric regulation Cooperativity Enzyme inhibitor

Classification	EC number Enzyme superfamily Enzyme family List of enzymes

Kinetics	Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics

Types	EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list)

Hexokinase deficiency is a genetic autosomal recessive disease that causes Chronic Haemolytic Anaemia. Chronic Haemolytic Anaemia is caused by a mutation in the HK gene, which codes for the HK enzyme. The mutation causes a reduction of the HK activity, which causes hexokinase deficiency. ^[1]

^ "Hexokinase deficiency". Enerca. Enerca. Retrieved 04-6-17. Check date values in: |access-date= (help)

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.

Hexokinase Provide feedback

Hexokinase ( EC:2.7.1.1) contains two structurally similar domains represented by this family and PF03727. Some members of the family have two copies of each of these domains.

Literature references

Bennett WS Jr, Steitz TA; , J Mol Biol 1980;140:211-230.: Structure of a complex between yeast hexokinase A and glucose. II. Detailed comparisons of conformation and active site configuration with the native hexokinase B monomer and dimer. PUBMED:7001032 EPMC:7001032
Steitz TA; , J Mol Biol 1971;61:695-700.: Structure of yeast hexokinase-B. I. Preliminary x-ray studies and subunit structure. PUBMED:5133118 EPMC:5133118

Internal database links

SCOOP:

OrfB_IS605

External database links

HOMSTRAD:	hexokinase
PRINTS:	PR00475
PROSITE:	PDOC00370
SCOP:	1cza

This tab holds annotation information from the InterPro database.

InterPro entry IPR022672

Hexokinase is an important enzyme that catalyses the ATP-dependent conversion of aldo- and keto-hexose sugars to the hexose-6-phosphate (H6P). The enzyme can catalyse this reaction on glucose, fructose, sorbitol and glucosamine, and as such is the first step in a number of metabolic pathways [PUBMED:1783373]. The addition of a phosphate group to the sugar acts to trap it in a cell, since the negatively charged phosphate cannot easily traverse the plasma membrane.

The enzyme is widely distributed in eukaryotes. There are three isozymes of hexokinase in yeast (PI, PII and glucokinase): isozymes PI and PII phosphorylate both aldo- and keto-sugars; glucokinase is specific for aldo-hexoses. All three isozymes contain two domains [PUBMED:1783373]. Structural studies of yeast hexokinase reveal a well-defined catalytic pocket that binds ATP and hexose, allowing easy transfer of the phosphate from ATP to the sugar [PUBMED:10749890]. Vertebrates contain four hexokinase isozymes, designated I to IV, where types I to III contain a duplication of the two-domain yeast-type hexokinases. Both the N- and C-terminal halves bind hexose and H6P, though in types I an III only the C-terminal half supports catalysis, while both halves support catalysis in type II. The N-terminal half is the regulatory region. Type IV hexokinase is similar to the yeast enzyme in containing only the two domains, and is sometimes incorrectly referred to as glucokinase.

The different vertebrate isozymes differ in their catalysis, localisation and regulation, thereby contributing to the different patterns of glucose metabolism in different tissues [PUBMED:12756287]. Whereas types I to III can phosphorylate a variety of hexose sugars and are inhibited by glucose-6-phosphate (G6P), type IV is specific for glucose and shows no G6P inhibition. Type I enzyme may have a catabolic function, producing H6P for energy production in glycolysis; it is bound to the mitochondrial membrane, which enables the coordination of glycolysis with the TCA cycle. Types II and III enzyme may have anabolic functions, providing H6P for glycogen or lipid synthesis. Type IV enzyme is found in the liver and pancreatic beta-cells, where it is controlled by insulin (activation) and glucagon (inhibition). In pancreatic beta-cells, type IV enzyme acts as a glucose sensor to modify insulin secretion. Mutations in type IV hexokinase have been associated with diabetes mellitus.

Hexokinase (EC), a fructose and glucose phosphorylating enzyme, contains two structurally similar domains represented by this family and . Some hexokinases have two copies of each of these domains. This entry represents the N-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	phosphotransferase activity, alcohol group as acceptor (GO:0016773)
Biological process	carbohydrate metabolic process (GO:0005975)

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 Actin_ATPase (CL0108), which has the following description:

The actin-like ATPase domain forms an alpha/beta canonical fold. The domain can be subdivided into 1A, 1B, 2A and 2B subdomains. Subdomains 1A and 1B share the same RNAseH-like fold (a five-stranded beta-sheet decorated by a number of alpha-helices). Domains 1A and 2A are conserved in all members of this superfamily, whereas domain 1B and 2B have a variable structure and are even missing from some homologues [1]. Within the actin-like ATPase domain the ATP-binding site is highly conserved. The phosphate part of the ATP is bound in a cleft between subdomains 1A and 2A, whereas the adenosine moiety is bound to residues from domains 2A and 2B[1].

The clan contains the following 31 members:

Acetate_kinase Actin Actin_micro AnmK BcrAD_BadFG Carbam_trans_N DDR DUF1464 DUF2229 EutA FGGY_C FGGY_N FtsA Fumble GDA1_CD39 Glucokinase Hexokinase_1 Hexokinase_2 HGD-D HSP70 Hydant_A_N Hydantoinase_A MreB_Mbl MutL Pan_kinase Peptidase_M22 PilM_2 Ppx-GppA ROK StbA T2SSL

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 (reference proteomes) using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the UniProtKB sequence database, 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
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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

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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 (436)	Full (3650)	Representative proteomes				UniProt (5706)	NCBI (8052)	Meta (7)
	Seed (436)	Full (3650)	RP15 (684)	RP35 (1715)	RP55 (2724)	RP75 (3601)	UniProt (5706)	NCBI (8052)	Meta (7)
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HTML	View	View
PP/heatmap	₁	View

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

Key: available, not generated, — not available.

Format an alignment

	Seed (436)	Full (3650)	Representative proteomes				UniProt (5706)	NCBI (8052)	Meta (7)
	Seed (436)	Full (3650)	RP15 (684)	RP35 (1715)	RP55 (2724)	RP75 (3601)	UniProt (5706)	NCBI (8052)	Meta (7)
Alignment:
Format:
Order:	Tree Alphabetical
Sequence:	Inserts lower case All upper case
Gaps:
Download/view:	Download View

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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 (436)	Full (3650)	Representative proteomes				UniProt (5706)	NCBI (8052)	Meta (7)
	Seed (436)	Full (3650)	RP15 (684)	RP35 (1715)	RP55 (2724)	RP75 (3601)	UniProt (5706)	NCBI (8052)	Meta (7)
Raw Stockholm	Download	Download	Download	Download	Download	Download	Download	Download	Download
Gzipped	Download	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.

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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:

hexokinase;

Type:

Domain

Author:

Sonnhammer ELL, Finn RD, Griffiths-Jones SR

Number in seed:

436

Number in full:

3650

Average length of the domain:

191.10 aa

Average identity of full alignment:

35 %

Average coverage of the sequence by the domain:

40.23 %

HMM information

HMM build commands:

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

search method: hmmsearch -Z 26740544 -E 1000 --cpu 4 HMM pfamseq

Model details:

Parameter	Sequence	Domain
Gathering cut-off	24.3	24.3
Trusted cut-off	24.3	24.4
Noise cut-off	24.2	24.2

Model length:

196

Family (HMM) version:

20

Download:

download the raw HMM for this family

Species distribution

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Colour assignments

Archea	Eukaryota
Bacteria	Other sequences
Viruses	Unclassified
Viroids	Unclassified sequence

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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.

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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.

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superkingdom
kingdom
phylum
class
order
family
genus
species

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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.

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Tree controls

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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

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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 3 interactions for this family. More...

Hexokinase_1 Hexokinase_2 Hexokinase_2

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 Hexokinase_1 domain has been found. There are 114 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.

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Family: Hexokinase_1 (PF00349)

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Summary: Hexokinase

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Hexokinase Edit Wikipedia article

Contents

Variation

Reaction

Consequences of hexose phosphorylation

Size of different isoforms

Types of mammalian hexokinase

Hexokinases I, II, and III

Hexokinase IV ("glucokinase")

Hexokinase in glycolysis

Association with mitochondria

Hydropathy plot

See also

References

Hexokinase Provide feedback

Literature references

Internal database links

External database links

InterPro entry IPR022672

Gene Ontology

Domain organisation

Pfam Clan

Alignments

Alignment types

Viewing

Reformatting

Downloading

View options

Format an alignment

Download options

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