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155  structures 1517  species 0  interactions 9183  sequences 117  architectures

Family: Hexokinase_1 (PF00349)

Summary: Hexokinase

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Hexokinase". More...

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

  1. 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

  2. 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

External database links

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.

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 34 members:

Acetate_kinase Actin Actin_micro ALP_N 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 HypF_C MreB_Mbl MutL Pan_kinase PilM_2 Ppx-GppA RACo_C_ter ROK StbA T2SSL TsaD

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 and the UniProtKB sequence database. More...

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
(379)
Full
(9183)
Representative proteomes UniProt
(14965)
RP15
(1125)
RP35
(3489)
RP55
(7079)
RP75
(9782)
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PP/heatmap 1            

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

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(379)
Full
(9183)
Representative proteomes UniProt
(14965)
RP15
(1125)
RP35
(3489)
RP55
(7079)
RP75
(9782)
Alignment:
Format:
Order:
Sequence:
Gaps:
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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
(379)
Full
(9183)
Representative proteomes UniProt
(14965)
RP15
(1125)
RP35
(3489)
RP55
(7079)
RP75
(9782)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download  
Gzipped 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.

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 View help on the curation process

Seed source: Prosite
Previous IDs: hexokinase;
Type: Domain
Sequence Ontology: SO:0000417
Author: Sonnhammer ELL , Finn RD , Griffiths-Jones SR
Number in seed: 379
Number in full: 9183
Average length of the domain: 188.20 aa
Average identity of full alignment: 38 %
Average coverage of the sequence by the domain: 40.54 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 57096847 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 24.3 24.3
Trusted cut-off 24.4 24.4
Noise cut-off 24.2 24.0
Model length: 200
Family (HMM) version: 23
Download: download the raw HMM for this family

Species distribution

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Archea Archea Eukaryota Eukaryota
Bacteria Bacteria Other sequences Other sequences
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Viroids Viroids Unclassified sequence Unclassified sequence

Selections

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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 155 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 sequence.

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AlphaFold Structure Predictions

The list of proteins below match this family and have AlphaFold predicted structures. Click on the protein accession to view the predicted structure.

Protein Predicted structure External Information
A0A0R0GN50 View 3D Structure Click here
A0A0R0J250 View 3D Structure Click here
A0A0R0JZ56 View 3D Structure Click here
A0A1D6MAK9 View 3D Structure Click here
A0A1D6N1P8 View 3D Structure Click here
A0A1D6NCX2 View 3D Structure Click here
A0A2R8QAA9 View 3D Structure Click here
A0A2R8QAA9 View 3D Structure Click here
A4HZB1 View 3D Structure Click here
A4HZB2 View 3D Structure Click here
B4FB85 View 3D Structure Click here
B6UBW9 View 3D Structure Click here
B7ZYX4 View 3D Structure Click here
B8JKC9 View 3D Structure Click here
B8JKC9 View 3D Structure Click here
C0HF79 View 3D Structure Click here
C6KT76 View 3D Structure Click here
F1RC38 View 3D Structure Click here
I1J4I1 View 3D Structure Click here
I1J4I4 View 3D Structure Click here
I1JAF6 View 3D Structure Click here
I1K5Z4 View 3D Structure Click here
I1KJB0 View 3D Structure Click here
I1KPW6 View 3D Structure Click here
I1KV15 View 3D Structure Click here
I1L3C1 View 3D Structure Click here
I1LG62 View 3D Structure Click here
I1LIM1 View 3D Structure Click here
I1MVG1 View 3D Structure Click here
I1MY29 View 3D Structure Click here
K7LSL4 View 3D Structure Click here
K7VX77 View 3D Structure Click here
K7W1K3 View 3D Structure Click here
M0R3X7 View 3D Structure Click here
O08528 View 3D Structure Click here
O08528 View 3D Structure Click here
P04806 View 3D Structure Click here
P04807 View 3D Structure Click here
P05708 View 3D Structure Click here
P05708 View 3D Structure Click here
P17709 View 3D Structure Click here
P17710 View 3D Structure Click here
P17710 View 3D Structure Click here
P17712 View 3D Structure Click here
P19367 View 3D Structure Click here
P19367 View 3D Structure Click here
P27881 View 3D Structure Click here
P27881 View 3D Structure Click here
P27926 View 3D Structure Click here
P27926 View 3D Structure Click here
P35557 View 3D Structure Click here
P50521 View 3D Structure Click here
P52789 View 3D Structure Click here
P52789 View 3D Structure Click here
P52790 View 3D Structure Click here
P52790 View 3D Structure Click here
P52792 View 3D Structure Click here
P83776 View 3D Structure Click here
P93834 View 3D Structure Click here
Q04409 View 3D Structure Click here
Q06204 View 3D Structure Click here
Q09756 View 3D Structure Click here
Q19440 View 3D Structure Click here
Q1WM15 View 3D Structure Click here
Q1WM16 View 3D Structure Click here
Q2KNB4 View 3D Structure Click here
Q2KNB5 View 3D Structure Click here
Q2KNB7 View 3D Structure Click here
Q2KNB9 View 3D Structure Click here
Q2TB90 View 3D Structure Click here
Q2TB90 View 3D Structure Click here
Q3TRM8 View 3D Structure Click here
Q3TRM8 View 3D Structure Click here
Q42525 View 3D Structure Click here
Q4D3P5 View 3D Structure Click here
Q4DQ27 View 3D Structure Click here
Q56XE8 View 3D Structure Click here
Q59RR7 View 3D Structure Click here
Q59RW5 View 3D Structure Click here
Q59TZ8 View 3D Structure Click here
Q5W676 View 3D Structure Click here
Q6NX09 View 3D Structure Click here
Q6NX09 View 3D Structure Click here
Q6Z398 View 3D Structure Click here
Q7JYW9 View 3D Structure Click here
Q8LH82 View 3D Structure Click here
Q8LQ68 View 3D Structure Click here
Q91W97 View 3D Structure Click here
Q91W97 View 3D Structure Click here
Q9FZG4 View 3D Structure Click here
Q9LPS1 View 3D Structure Click here
Q9N4A5 View 3D Structure Click here
Q9NFT7 View 3D Structure Click here
Q9NFT9 View 3D Structure Click here
Q9T071 View 3D Structure Click here
Q9W330 View 3D Structure Click here
Q9XU15 View 3D Structure Click here