P17710 · HXK1_MOUSE
- ProteinHexokinase-1
- GeneHk1
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids974 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Catalyzes the phosphorylation of various hexoses, such as D-glucose, D-glucosamine, D-fructose, D-mannose and 2-deoxy-D-glucose, to hexose 6-phosphate (D-glucose 6-phosphate, D-glucosamine 6-phosphate, D-fructose 6-phosphate, D-mannose 6-phosphate and 2-deoxy-D-glucose 6-phosphate, respectively). Does not phosphorylate N-acetyl-D-glucosamine (By similarity).
Mediates the initial step of glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-phosphate (By similarity).
Involved in innate immunity and inflammation by acting as a pattern recognition receptor for bacterial peptidoglycan. When released in the cytosol, N-acetyl-D-glucosamine component of bacterial peptidoglycan inhibits the hexokinase activity of HK1 and causes its dissociation from mitochondrial outer membrane, thereby activating the NLRP3 inflammasome (PubMed:27374331).
Mediates the initial step of glycolysis by catalyzing phosphorylation of D-glucose to D-glucose 6-phosphate (By similarity).
Involved in innate immunity and inflammation by acting as a pattern recognition receptor for bacterial peptidoglycan. When released in the cytosol, N-acetyl-D-glucosamine component of bacterial peptidoglycan inhibits the hexokinase activity of HK1 and causes its dissociation from mitochondrial outer membrane, thereby activating the NLRP3 inflammasome (PubMed:27374331).
Catalytic activity
- a D-hexose + ATP = a D-hexose 6-phosphate + ADP + H+This reaction proceeds in the forward direction.
Activity regulation
Hexokinase is an allosteric enzyme inhibited by its product D-glucose 6-phosphate. Hexokinase activity is inhibited by N-acetyl-D-glucosamine.
Pathway
Carbohydrate metabolism; hexose metabolism.
Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 1/4.
Features
Showing features for binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 86 | ATP 1 (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 140-145 | ATP 1 (UniProtKB | ChEBI) | ||||
Sequence: DLGGSS | ||||||
Binding site | 140-147 | D-glucose 6-phosphate 1 (UniProtKB | ChEBI) | ||||
Sequence: DLGGSSFR | ||||||
Binding site | 211 | D-glucose 1 (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 228-229 | D-glucose 1 (UniProtKB | ChEBI) | ||||
Sequence: TK | ||||||
Binding site | 264-265 | D-glucose 1 (UniProtKB | ChEBI) | ||||
Sequence: ND | ||||||
Binding site | 265 | D-glucose 6-phosphate 1 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 288 | D-glucose 6-phosphate 1 (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 291 | D-glucose 1 (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 316 | D-glucose 1 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 347-350 | D-glucose 1 (UniProtKB | ChEBI) | ||||
Sequence: QLFE | ||||||
Binding site | 469-471 | D-glucose 6-phosphate 1 (UniProtKB | ChEBI) | ||||
Sequence: DGS | ||||||
Binding site | 481-482 | ATP 1 (UniProtKB | ChEBI) | ||||
Sequence: RR | ||||||
Binding site | 505 | D-glucose 6-phosphate 1 (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 588-592 | D-glucose 6-phosphate 2 (UniProtKB | ChEBI) | ||||
Sequence: DLGGT | ||||||
Binding site | 588-593 | ATP 2 (UniProtKB | ChEBI) | ||||
Sequence: DLGGTN | ||||||
Binding site | 659-660 | D-glucose 2 (UniProtKB | ChEBI) | ||||
Sequence: SF | ||||||
Binding site | 676-677 | D-glucose 2 (UniProtKB | ChEBI) | ||||
Sequence: TK | ||||||
Binding site | 712-713 | D-glucose 2 (UniProtKB | ChEBI) | ||||
Sequence: ND | ||||||
Binding site | 713 | D-glucose 6-phosphate 2 (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 736 | ATP 2 (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 736 | D-glucose 6-phosphate 2 (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 738-739 | D-glucose 2 (UniProtKB | ChEBI) | ||||
Sequence: SN | ||||||
Binding site | 764 | D-glucose 2 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 798 | D-glucose 2 (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 803-804 | ATP 2 (UniProtKB | ChEBI) | ||||
Sequence: GM | ||||||
Binding site | 840-844 | ATP 2 (UniProtKB | ChEBI) | ||||
Sequence: TKFLS | ||||||
Binding site | 917-919 | D-glucose 6-phosphate 2 (UniProtKB | ChEBI) | ||||
Sequence: DGT | ||||||
Binding site | 919-923 | ATP 2 (UniProtKB | ChEBI) | ||||
Sequence: TLYKL | ||||||
Binding site | 953 | D-glucose 6-phosphate 2 (UniProtKB | ChEBI) | ||||
Sequence: S |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameHexokinase-1
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionP17710
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Mitochondrion outer membrane ; Peripheral membrane protein
Note: The mitochondrial-binding peptide (MBP) region promotes association with the mitochondrial outer membrane (By similarity).
Dissociates from the mitochondrial outer membrane following inhibition by N-acetyl-D-glucosamine, leading to relocation to the cytosol (PubMed:27374331).
Dissociates from the mitochondrial outer membrane following inhibition by N-acetyl-D-glucosamine, leading to relocation to the cytosol (PubMed:27374331).
Isoform HK1
Mitochondrion outer membrane ; Peripheral membrane protein
Isoform HK1-SC
Note: Isoform HK1-SC is an integral membrane protein.
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 67 | Disrupts targeting to membrane; when associated with N-68; Q-70; P-73; A-74 and Q-75. | ||||
Sequence: P → A | ||||||
Mutagenesis | 68 | Disrupts targeting to membrane; when associated with A-67; Q-70; P-73; A-74 and Q-75. | ||||
Sequence: K → N | ||||||
Mutagenesis | 70 | Disrupts targeting to membrane; when associated with A-67; N-68; P-73; A-74 and Q-75. | ||||
Sequence: R → Q | ||||||
Mutagenesis | 73 | Disrupts targeting to membrane; when associated with A-67; N-68; Q-70; A-74 and Q-75. | ||||
Sequence: L → P | ||||||
Mutagenesis | 74 | Disrupts targeting to membrane; when associated with A-67; N-68; Q-70; P-73 and Q-75. | ||||
Sequence: T → A | ||||||
Mutagenesis | 75 | Disrupts targeting to membrane; when associated with A-67; N-68; Q-70; P-73 and A-74. | ||||
Sequence: E → Q |
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000013399 | 1-974 | Hexokinase-1 | |||
Sequence: MGWGAPLLSRMLHGPGQAGETSPVPERQSGSENPASEDRRPLEKQCSHHLYTMGQNCQRGQAVDVEPKIRPPLTEEKIDKYLYAMRLSDEILIDILTRFKKEMKNGLSRDYNPTASVKMLPTFVRSIPDGSEKGDFIALDLGGSSFRILRVQVNHEKSQNVSMESEVYDTPENIVHGSGSQLFDHVAECLGDFMEKRKIKDKKLPVGFTFSFPCRQSKIDEAVLITWTKRFKASGVEGADVVKLLNKAIKKRGDYDANIVAVVNDTVGTMMTCGYDDQQCEVGLIIGTGTNACYMEELRHIDLVEGDEGRMCINTEWGAFGDDGSLEDIRTEFDRELDRGSLNPGKQLFEKMVSGMYMGELVRLILVKMAKESLLFEGRITPELLTRGKFTTSDVAAIETDKEGVQNAKEILTRLGVEPSHDDCVSVQHVCTIVSFRSANLVAATLGAILNRLRDNKGTPRLRTTVGVDGSLYKMHPQYSRRFHKTLRRLVPDSDVRFLLSESGSGKGAAMVTAVAYRLAEQHRQIEETLSHFRLSKQALMEVKKKLRSEMEMGLRKETNSRATVKMLPSYVRSIPDGTEHGDFLALDLGGTNFRVLLVKIRSGKKRTVEMHNKIYSIPLEIMQGTGDELFDHIVSCISDFLDYMGIKGPRMPLGFTFSFPCKQTSLDCGILITWTKGFKATDCVGHDVATLLRDAVKRREEFDLDVVAVVNDTVGTMMTCAYEEPSCEIGLIVGTGSNACYMEEMKNVEMVEGNQGQMCINMEWGAFGDNGCLDDIRTDFDKVVDEYSLNSGKQRFEKMISGMYLGEIVRNILIDFTKKGFLFRGQISEPLKTRGIFETKFLSQIESDRLALLQVRAILQQLGLNSTCDDSILVKTVCGVVSKRAAQLCGAGMAAVVEKIRENRGLDHLNVTVGVDGTLYKLHPHFSRIMHQTVKELSPKCTVSFLLSEDGSGKGAALITAVGVRLRGDPTNA | ||||||
Modified residue | 393 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Isoform HK1-SC
Tyrosine-phosphorylated.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
In rapidly growing tumor cells exhibiting high glucose catabolic rates, isoform HK1 is markedly elevated. Isoform HK1-SA, isoform HK1-SB and isoform HK1-SC are found only in spermatogenic cells. Isoform HK1-SC is detected in round spermatids, condensing spermatids and mature sperm where it is found in the head membranes, mitochondria of the midpiece and the fibrous sheath of the flagellum. Expressed within the principal piece and midpiece of sperm tail (at protein level).
Developmental stage
Isoform HK1-SA: First expressed during meiosis and continues to be present in postmeiotic germ cells (PubMed:8396993, PubMed:9450953).
Isoform HK1-SB: Present only in postmeiotic germ cells (PubMed:8396993).
Isoform HK1-SB: Present only in postmeiotic germ cells (PubMed:8396993).
Gene expression databases
Interaction
Subunit
Monomer (By similarity).
Interacts with RABL2/RABL2A; binds preferentially to GTP-bound RABL2 (PubMed:23055941).
Interacts with VDAC1. The HK1-VDAC1 complex interacts with ATF2 (By similarity).
Interacts (via N-terminal spermatogenic cell-specific region) with PFKM isoform 2 and isoform 3 (via C-terminus) (PubMed:19889946).
Interacts with SMAD5 (By similarity).
Interacts with RABL2/RABL2A; binds preferentially to GTP-bound RABL2 (PubMed:23055941).
Interacts with VDAC1. The HK1-VDAC1 complex interacts with ATF2 (By similarity).
Interacts (via N-terminal spermatogenic cell-specific region) with PFKM isoform 2 and isoform 3 (via C-terminus) (PubMed:19889946).
Interacts with SMAD5 (By similarity).
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-42 | Disordered | ||||
Sequence: MGWGAPLLSRMLHGPGQAGETSPVPERQSGSENPASEDRRPL | ||||||
Region | 57-66 | Mitochondrial-binding peptide (MBP) | ||||
Sequence: CQRGQAVDVE | ||||||
Domain | 72-514 | Hexokinase 1 | ||||
Sequence: PLTEEKIDKYLYAMRLSDEILIDILTRFKKEMKNGLSRDYNPTASVKMLPTFVRSIPDGSEKGDFIALDLGGSSFRILRVQVNHEKSQNVSMESEVYDTPENIVHGSGSQLFDHVAECLGDFMEKRKIKDKKLPVGFTFSFPCRQSKIDEAVLITWTKRFKASGVEGADVVKLLNKAIKKRGDYDANIVAVVNDTVGTMMTCGYDDQQCEVGLIIGTGTNACYMEELRHIDLVEGDEGRMCINTEWGAFGDDGSLEDIRTEFDRELDRGSLNPGKQLFEKMVSGMYMGELVRLILVKMAKESLLFEGRITPELLTRGKFTTSDVAAIETDKEGVQNAKEILTRLGVEPSHDDCVSVQHVCTIVSFRSANLVAATLGAILNRLRDNKGTPRLRTTVGVDGSLYKMHPQYSRRFHKTLRRLVPDSDVRFLLSESGSGKGAAMVTA | ||||||
Region | 129-263 | Hexokinase small subdomain 1 | ||||
Sequence: DGSEKGDFIALDLGGSSFRILRVQVNHEKSQNVSMESEVYDTPENIVHGSGSQLFDHVAECLGDFMEKRKIKDKKLPVGFTFSFPCRQSKIDEAVLITWTKRFKASGVEGADVVKLLNKAIKKRGDYDANIVAVV | ||||||
Region | 264-503 | Hexokinase large subdomain 1 | ||||
Sequence: NDTVGTMMTCGYDDQQCEVGLIIGTGTNACYMEELRHIDLVEGDEGRMCINTEWGAFGDDGSLEDIRTEFDRELDRGSLNPGKQLFEKMVSGMYMGELVRLILVKMAKESLLFEGRITPELLTRGKFTTSDVAAIETDKEGVQNAKEILTRLGVEPSHDDCVSVQHVCTIVSFRSANLVAATLGAILNRLRDNKGTPRLRTTVGVDGSLYKMHPQYSRRFHKTLRRLVPDSDVRFLLSES | ||||||
Domain | 520-962 | Hexokinase 2 | ||||
Sequence: AEQHRQIEETLSHFRLSKQALMEVKKKLRSEMEMGLRKETNSRATVKMLPSYVRSIPDGTEHGDFLALDLGGTNFRVLLVKIRSGKKRTVEMHNKIYSIPLEIMQGTGDELFDHIVSCISDFLDYMGIKGPRMPLGFTFSFPCKQTSLDCGILITWTKGFKATDCVGHDVATLLRDAVKRREEFDLDVVAVVNDTVGTMMTCAYEEPSCEIGLIVGTGSNACYMEEMKNVEMVEGNQGQMCINMEWGAFGDNGCLDDIRTDFDKVVDEYSLNSGKQRFEKMISGMYLGEIVRNILIDFTKKGFLFRGQISEPLKTRGIFETKFLSQIESDRLALLQVRAILQQLGLNSTCDDSILVKTVCGVVSKRAAQLCGAGMAAVVEKIRENRGLDHLNVTVGVDGTLYKLHPHFSRIMHQTVKELSPKCTVSFLLSEDGSGKGAALITA | ||||||
Region | 577-711 | Hexokinase small subdomain 2 | ||||
Sequence: DGTEHGDFLALDLGGTNFRVLLVKIRSGKKRTVEMHNKIYSIPLEIMQGTGDELFDHIVSCISDFLDYMGIKGPRMPLGFTFSFPCKQTSLDCGILITWTKGFKATDCVGHDVATLLRDAVKRREEFDLDVVAVV | ||||||
Region | 712-951 | Hexokinase large subdomain 2 | ||||
Sequence: NDTVGTMMTCAYEEPSCEIGLIVGTGSNACYMEEMKNVEMVEGNQGQMCINMEWGAFGDNGCLDDIRTDFDKVVDEYSLNSGKQRFEKMISGMYLGEIVRNILIDFTKKGFLFRGQISEPLKTRGIFETKFLSQIESDRLALLQVRAILQQLGLNSTCDDSILVKTVCGVVSKRAAQLCGAGMAAVVEKIRENRGLDHLNVTVGVDGTLYKLHPHFSRIMHQTVKELSPKCTVSFLLSED |
Domain
The N- and C-terminal halves of this hexokinase contain a hexokinase domain. The catalytic activity is associated with the C-terminus while regulatory function is associated with the N-terminus. Each domain can bind a single D-glucose and D-glucose 6-phosphate molecule.
Sequence similarities
Belongs to the hexokinase family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoforms
- Sequence statusComplete
This entry describes 4 isoforms produced by Alternative splicing & Alternative initiation.
P17710-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- NameHK1-SA
- Length974
- Mass (Da)108,303
- Last updated2011-07-27 v3
- Checksum6122505622F7BA3D
P17710-2
- NameHK1-SB
- NoteProduced by alternative splicing and alternative initiation at Met-53 of isoform HK1-SA.
P17710-3
- NameHK1
- NoteProduced by alternative splicing and alternative initiation at Met-53 of isoform HK1-SA.
- Differences from canonical
- 1-76: MGWGAPLLSRMLHGPGQAGETSPVPERQSGSENPASEDRRPLEKQCSHHLYTMGQNCQRGQAVDVEPKIRPPLTEE → MIAAQLLAYYFTELKDDQVK
P17710-4
- NameHK1-SC
- NoteProduced by alternative initiation at Met-53 of isoform HK1-SA.
- Differences from canonical
- 1-52: Missing
Computationally mapped potential isoform sequences
There are 6 potential isoforms mapped to this entry
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_018747 | 1-52 | in isoform HK1-SB and isoform HK1-SC | |||
Sequence: Missing | ||||||
Alternative sequence | VSP_007327 | 1-76 | in isoform HK1 | |||
Sequence: MGWGAPLLSRMLHGPGQAGETSPVPERQSGSENPASEDRRPLEKQCSHHLYTMGQNCQRGQAVDVEPKIRPPLTEE → MIAAQLLAYYFTELKDDQVK | ||||||
Alternative sequence | VSP_007328 | 400 | in isoform HK1-SB | |||
Sequence: T → TGWELSPDRRWYQAYMRCTQDTHR | ||||||
Sequence conflict | 870 | in Ref. 1; AAA37804 | ||||
Sequence: D → S | ||||||
Sequence conflict | 899 | in Ref. 2; AAB57759 | ||||
Sequence: E → Q |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
J05277 EMBL· GenBank· DDBJ | AAA37804.1 EMBL· GenBank· DDBJ | mRNA | ||
L16948 EMBL· GenBank· DDBJ | AAB57760.1 EMBL· GenBank· DDBJ | mRNA | ||
L16949 EMBL· GenBank· DDBJ | AAB57759.1 EMBL· GenBank· DDBJ | mRNA | ||
L16950 EMBL· GenBank· DDBJ | AAA53036.1 EMBL· GenBank· DDBJ | mRNA | ||
AC126428 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AC145297 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. |