Protein:HK1 |
Protein Summary |
 Gene summary |
| Gene name: HK1 | ASpdb.0 ID: 3098 | Gene | Gene symbol | HK1 | Gene ID | 3098 |
| Gene name | hexokinase 1 |
| Synonyms | HK|HK1-ta|HK1-tb|HK1-tc|HKD|HKI|HMSNR|HXK1|NEDVIBA|NMSR|RP79|hexokinase |
| Cytomap | 10q22.1 |
| Type of gene | protein-coding |
| Description | hexokinase-1Neuropathy, hereditary motor and sensory, Russe typebrain form hexokinaseglycolytic enzymehexokinase IRhexokinase type Ihexokinase-A |
| Modification date | 20240407 |
| UniProtAcc | P19367 |
| Gene ontology of this gene with evidence of Inferred from Direct Assay (IDA) from Entrez |
| Partner | Gene | GO ID | GO term | PubMed ID |
| Gene | HK1 | GO:0005739 | mitochondrion | - |
| Gene | HK1 | GO:0042834 | peptidoglycan binding | 27374331 |
AS Summary |
| Information of the canonical protein with experimentally identified structure from PDB (2023). |
| UniProt Acc | File name | PDB ID | Method | Resolution | Chain | Start | End |
| P19367-1 | P19367-1_1qha_A.pdb | 1QHA | X-ray | 2.25 | A | 12 | 914 |
| ASpdb's canonical and alternatively spliced isoform information. |
| accession_id | gene_name | canonical_id | alternative_id | canonical_length | alternative_length | canonical_start | canonical_end | type | originalSEQ | variationSEQ | alternative_start | alternative_end |
| P19367 | HK1 | P19367-1 | P19367-2 | 917 | 916 | 1 | 21 | Substitution | MIAAQLLAYYFTELKDDQVKK | MDCEHSLSLPCRGAEAWEIG | 1 | 20 |
| P19367 | HK1 | P19367-1 | P19367-3 | 917 | 921 | 1 | 21 | Substitution | MIAAQLLAYYFTELKDDQVKK | MGQICQRESATAAEKPKLHLLAESE | 1 | 25 |
| P19367 | HK1 | P19367-1 | P19367-4 | 917 | 905 | 1 | 21 | Substitution | MIAAQLLAYYFTELKDDQVKK | MAKRALHDF | 1 | 9 |
| Multiple sequence alignment of our canonical and alternatively spliced HK1 |
| Matched gene isoform IDs with Ensembl and RefSeq of our canonical and alternative spliced genes of HK1 |
| UniProt-id | ENSG | ENST | ENSP |
| P19367-1 | ENSG00000156515.25 | ENST00000359426.7 | ENSP00000352398.6 |
| P19367-2 | ENSG00000156515.25 | ENST00000298649.8 | ENSP00000298649.3 |
| P19367-3 | ENSG00000156515.25 | ENST00000436817.6 | ENSP00000415949.2 |
| P19367-3 | ENSG00000156515.25 | ENST00000643399.2 | ENSP00000494664.1 |
| UniProt-id | NM ID | NP ID |
| P19367-1 | NM_000188.2 | NP_000179.2 |
| P19367-2 | NM_033496.2 | NP_277031.1 |
| P19367-3 | NM_001322364.1 | NP_001309293.1 |
| P19367-3 | NM_033497.2 | NP_277032.1 |
| P19367-3 | NM_033498.2 | NP_277033.1 |
| P19367-4 | NM_033500.2 | NP_277035.2 |
| Amino acid sequences of our canonical and alternatively spliced HK1 |
| accession_id | Protein sequence |
| P19367-1 | MIAAQLLAYYFTELKDDQVKKIDKYLYAMRLSDETLIDIMTRFRKEMKNGLSRDFNPTATVKMLPTFVRSIPDGSEKGDFIALDLGGSSF RILRVQVNHEKNQNVHMESEVYDTPENIVHGSGSQLFDHVAECLGDFMEKRKIKDKKLPVGFTFSFPCQQSKIDEAILITWTKRFKASGV EGADVVKLLNKAIKKRGDYDANIVAVVNDTVGTMMTCGYDDQHCEVGLIIGTGTNACYMEELRHIDLVEGDEGRMCINTEWGAFGDDGSL EDIRTEFDREIDRGSLNPGKQLFEKMVSGMYLGELVRLILVKMAKEGLLFEGRITPELLTRGKFNTSDVSAIEKNKEGLHNAKEILTRLG VEPSDDDCVSVQHVCTIVSFRSANLVAATLGAILNRLRDNKGTPRLRTTVGVDGSLYKTHPQYSRRFHKTLRRLVPDSDVRFLLSESGSG KGAAMVTAVAYRLAEQHRQIEETLAHFHLTKDMLLEVKKRMRAEMELGLRKQTHNNAVVKMLPSFVRRTPDGTENGDFLALDLGGTNFRV LLVKIRSGKKRTVEMHNKIYAIPIEIMQGTGEELFDHIVSCISDFLDYMGIKGPRMPLGFTFSFPCQQTSLDAGILITWTKGFKATDCVG HDVVTLLRDAIKRREEFDLDVVAVVNDTVGTMMTCAYEEPTCEVGLIVGTGSNACYMEEMKNVEMVEGDQGQMCINMEWGAFGDNGCLDD IRTHYDRLVDEYSLNAGKQRYEKMISGMYLGEIVRNILIDFTKKGFLFRGQISETLKTRGIFETKFLSQIESDRLALLQVRAILQQLGLN STCDDSILVKTVCGVVSRRAAQLCGAGMAAVVDKIRENRGLDRLNVTVGVDGTLYKLHPHFSRIMHQTVKELSPKCNVSFLLSEDGSGKG |
| P19367-2 | MDCEHSLSLPCRGAEAWEIGIDKYLYAMRLSDETLIDIMTRFRKEMKNGLSRDFNPTATVKMLPTFVRSIPDGSEKGDFIALDLGGSSFR ILRVQVNHEKNQNVHMESEVYDTPENIVHGSGSQLFDHVAECLGDFMEKRKIKDKKLPVGFTFSFPCQQSKIDEAILITWTKRFKASGVE GADVVKLLNKAIKKRGDYDANIVAVVNDTVGTMMTCGYDDQHCEVGLIIGTGTNACYMEELRHIDLVEGDEGRMCINTEWGAFGDDGSLE DIRTEFDREIDRGSLNPGKQLFEKMVSGMYLGELVRLILVKMAKEGLLFEGRITPELLTRGKFNTSDVSAIEKNKEGLHNAKEILTRLGV EPSDDDCVSVQHVCTIVSFRSANLVAATLGAILNRLRDNKGTPRLRTTVGVDGSLYKTHPQYSRRFHKTLRRLVPDSDVRFLLSESGSGK GAAMVTAVAYRLAEQHRQIEETLAHFHLTKDMLLEVKKRMRAEMELGLRKQTHNNAVVKMLPSFVRRTPDGTENGDFLALDLGGTNFRVL LVKIRSGKKRTVEMHNKIYAIPIEIMQGTGEELFDHIVSCISDFLDYMGIKGPRMPLGFTFSFPCQQTSLDAGILITWTKGFKATDCVGH DVVTLLRDAIKRREEFDLDVVAVVNDTVGTMMTCAYEEPTCEVGLIVGTGSNACYMEEMKNVEMVEGDQGQMCINMEWGAFGDNGCLDDI RTHYDRLVDEYSLNAGKQRYEKMISGMYLGEIVRNILIDFTKKGFLFRGQISETLKTRGIFETKFLSQIESDRLALLQVRAILQQLGLNS TCDDSILVKTVCGVVSRRAAQLCGAGMAAVVDKIRENRGLDRLNVTVGVDGTLYKLHPHFSRIMHQTVKELSPKCNVSFLLSEDGSGKGA |
| P19367-3 | MGQICQRESATAAEKPKLHLLAESEIDKYLYAMRLSDETLIDIMTRFRKEMKNGLSRDFNPTATVKMLPTFVRSIPDGSEKGDFIALDLG GSSFRILRVQVNHEKNQNVHMESEVYDTPENIVHGSGSQLFDHVAECLGDFMEKRKIKDKKLPVGFTFSFPCQQSKIDEAILITWTKRFK ASGVEGADVVKLLNKAIKKRGDYDANIVAVVNDTVGTMMTCGYDDQHCEVGLIIGTGTNACYMEELRHIDLVEGDEGRMCINTEWGAFGD DGSLEDIRTEFDREIDRGSLNPGKQLFEKMVSGMYLGELVRLILVKMAKEGLLFEGRITPELLTRGKFNTSDVSAIEKNKEGLHNAKEIL TRLGVEPSDDDCVSVQHVCTIVSFRSANLVAATLGAILNRLRDNKGTPRLRTTVGVDGSLYKTHPQYSRRFHKTLRRLVPDSDVRFLLSE SGSGKGAAMVTAVAYRLAEQHRQIEETLAHFHLTKDMLLEVKKRMRAEMELGLRKQTHNNAVVKMLPSFVRRTPDGTENGDFLALDLGGT NFRVLLVKIRSGKKRTVEMHNKIYAIPIEIMQGTGEELFDHIVSCISDFLDYMGIKGPRMPLGFTFSFPCQQTSLDAGILITWTKGFKAT DCVGHDVVTLLRDAIKRREEFDLDVVAVVNDTVGTMMTCAYEEPTCEVGLIVGTGSNACYMEEMKNVEMVEGDQGQMCINMEWGAFGDNG CLDDIRTHYDRLVDEYSLNAGKQRYEKMISGMYLGEIVRNILIDFTKKGFLFRGQISETLKTRGIFETKFLSQIESDRLALLQVRAILQQ LGLNSTCDDSILVKTVCGVVSRRAAQLCGAGMAAVVDKIRENRGLDRLNVTVGVDGTLYKLHPHFSRIMHQTVKELSPKCNVSFLLSEDG |
| P19367-4 | MAKRALHDFIDKYLYAMRLSDETLIDIMTRFRKEMKNGLSRDFNPTATVKMLPTFVRSIPDGSEKGDFIALDLGGSSFRILRVQVNHEKN QNVHMESEVYDTPENIVHGSGSQLFDHVAECLGDFMEKRKIKDKKLPVGFTFSFPCQQSKIDEAILITWTKRFKASGVEGADVVKLLNKA IKKRGDYDANIVAVVNDTVGTMMTCGYDDQHCEVGLIIGTGTNACYMEELRHIDLVEGDEGRMCINTEWGAFGDDGSLEDIRTEFDREID RGSLNPGKQLFEKMVSGMYLGELVRLILVKMAKEGLLFEGRITPELLTRGKFNTSDVSAIEKNKEGLHNAKEILTRLGVEPSDDDCVSVQ HVCTIVSFRSANLVAATLGAILNRLRDNKGTPRLRTTVGVDGSLYKTHPQYSRRFHKTLRRLVPDSDVRFLLSESGSGKGAAMVTAVAYR LAEQHRQIEETLAHFHLTKDMLLEVKKRMRAEMELGLRKQTHNNAVVKMLPSFVRRTPDGTENGDFLALDLGGTNFRVLLVKIRSGKKRT VEMHNKIYAIPIEIMQGTGEELFDHIVSCISDFLDYMGIKGPRMPLGFTFSFPCQQTSLDAGILITWTKGFKATDCVGHDVVTLLRDAIK RREEFDLDVVAVVNDTVGTMMTCAYEEPTCEVGLIVGTGSNACYMEEMKNVEMVEGDQGQMCINMEWGAFGDNGCLDDIRTHYDRLVDEY SLNAGKQRYEKMISGMYLGEIVRNILIDFTKKGFLFRGQISETLKTRGIFETKFLSQIESDRLALLQVRAILQQLGLNSTCDDSILVKTV CGVVSRRAAQLCGAGMAAVVDKIRENRGLDRLNVTVGVDGTLYKLHPHFSRIMHQTVKELSPKCNVSFLLSEDGSGKGAALITAVGVRLR |
Protein Functional Features |
| Main function of this protein. (from UniProt) |
| HK1 (go to UniProt):P19367 |
| Retention analysis result of protein across 39 protein features of UniProt such as six molecule processing features, 13 region features, four site features, six amino acid modification features, two natural variation features, five experimental info features, and 3 secondary structure features. Here, because of limited space for viewing, we only show the protein feature retention information belong to the 13 regional features. All retention annotation result can be downloaded at * Minus value of BPloci means that the break pointn is located before the CDS. |
| - Retained protein feature among the 13 regional features. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| P19367 | Domain | 16 | 458 | Note=Hexokinase 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01084 | Type=Substitution;Start=1;End=21 |
| P19367 | Domain | 16 | 458 | Note=Hexokinase 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01084 | Type=Substitution;Start=1;End=21 |
| P19367 | Domain | 16 | 458 | Note=Hexokinase 1;Ontology_term=ECO:0000255;evidence=ECO:0000255|PROSITE-ProRule:PRU01084 | Type=Substitution;Start=1;End=21 |
| P19367 | Region | 1 | 10 | Note=Mitochondrial-binding peptide (MBP);Ontology_term=ECO:0000305;evidence=ECO:0000305|PubMed:1985912;Dbxref=PMID:1985912 | Type=Substitution;Start=1;End=21 |
| P19367 | Region | 1 | 10 | Note=Mitochondrial-binding peptide (MBP);Ontology_term=ECO:0000305;evidence=ECO:0000305|PubMed:1985912;Dbxref=PMID:1985912 | Type=Substitution;Start=1;End=21 |
| P19367 | Region | 1 | 10 | Note=Mitochondrial-binding peptide (MBP);Ontology_term=ECO:0000305;evidence=ECO:0000305|PubMed:1985912;Dbxref=PMID:1985912 | Type=Substitution;Start=1;End=21 |
Gene Isoform Structures and Expression Levels for HK1 |
| Gene structures of our canonical and alternative spliced genes of HK1 * Click on the image to open the UCSC genome browser with custom track showing this image in a new window. |
| Expression levels of gene isoforms across GTEx. |
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| Expression levels of gene isoforms across TCGA. |
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Protein Structures |
| PDB and CIF files of the predicted protein structures * Here we show the 3D structure of the proteins using Mol*. AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. Model confidence is shown from the pLDDT values per residue. pLDDT corresponds to the model’s prediction of its score on the local Distance Difference Test. It is a measure of local accuracy (from AlphfaFold website). To color code individual residues, we transformed individual PDB files into CIF format. |
| 3D view using mol* of P19367-1 |
| 3D view using mol* of P19367-2 |
| 3D view using mol* of P19367-3 |
| 3D view using mol* of P19367-4 |
pLDDT Score Distribution |
| pLDDT score distribution of the predicted protein structures from AlphaFold2 * AlphaFold produces a per-residue confidence score (pLDDT) between 0 and 100. |
| pLDDT distribution across the protein length of P19367-1 |
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| pLDDT distribution across the protein length of P19367-2 |
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| pLDDT distribution across the protein length of P19367-3 |
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| pLDDT distribution across the protein length of P19367-4 |
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Ramachandran Plot of Protein Structures |
| Ramachandran plot of the torsional angles - phi (φ)and psi (ψ) - of the residues (amino acids) contained in this protein peptide. |
| Ramachandran plot of P19367-1 |
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| Ramachandran plot of P19367-3 |
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| Ramachandran plot of P19367-4 |
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Potential Active Site Information |
| The potential binding sites of these proteins were identified using SiteMap, a module of the Schrodinger suite. |
| UniProt-id | Site score | Size | D score | Volume | Exposure | Enclosure | Contact | Phobic | Philic | Balance | Don/Acc | Residues |
| P19367-1 | 1.113 | 105 | 0.869 | 182.476 | 0.318 | 0.867 | 1.194 | 0.144 | 1.815 | 0.079 | 0.494 | 84,87,88,89,91,93,153,155,173,209,229,231,232,233, 413,414,415,418,446,447,448,449,450 |
| P19367-2 | 1.116 | 106 | 0.898 | 193.795 | 0.325 | 0.871 | 1.169 | 0.071 | 1.733 | 0.041 | 0.439 | 83,85,86,87,88,90,92,152,154,172,173,174,208,228,2 30,231,232,234,412,413,414,417,445,446,447,448,449 |
| P19367-3 | 1.111 | 113 | 0.819 | 188.993 | 0.327 | 0.864 | 1.156 | 0.105 | 1.962 | 0.054 | 0.513 | 88,89,91,92,93,95,97,159,177,213,233,235,236,237,4 17,418,419,422,450,451,452,453,454 |
| P19367-4 | 1.127 | 143 | 0.889 | 239.757 | 0.332 | 0.887 | 1.16 | 0.12 | 1.79 | 0.067 | 0.47 | 72,74,75,76,77,78,79,81,141,143,144,145,160,161,16 2,196,197,198,217,219,220,221,222,223,248,249,250, 279,282,401,402,403,406,434,435,436,437,438 |
Protein Structure and Feature Comparision |
| Protein Structure Comparision Using Template Modeling Scores (TM-score). |
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| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Canonical validated structure (PDB)(green) |
| 3D view using mol* of P19367-1_P19367-1_1qha_A.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical validated structure (PDB)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P19367-1_1qha_A_P19367-2.pdb |
| 3D view using mol* of P19367-1_1qha_A_P19367-3.pdb |
| 3D view using mol* of P19367-1_1qha_A_P19367-4.pdb |
| Protein Structure Comparision Visualization with mol*. between Canonical predicted structure (AF2)(orange) vs Alternative predicted structure (AF2)(green) |
| 3D view using mol* of P19367-1_P19367-2.pdb |
| 3D view using mol* of P19367-1_P19367-3.pdb |
| 3D view using mol* of P19367-1_P19367-4.pdb |
| Protein Feature Comparison of the protein sequendary structures among the protiens. |
| ./stats/secondary_structure/figure/P19367-1_vs_P19367-2.png |
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| ./stats/secondary_structure/figure/P19367-1_vs_P19367-3.png |
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| ./stats/secondary_structure/figure/P19367-1_vs_P19367-4.png |
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| Protein Feature Comparison of the relative accessible surface area (ASA) among the protiens. |
| ./stats/relative_asa/P19367-1_vs_P19367-2.png |
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| ./stats/relative_asa/P19367-1_vs_P19367-3.png |
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| ./stats/relative_asa/P19367-1_vs_P19367-4.png |
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Protein-Protein Interaction |
| Interactors from UniProt. |
| Accession_id | Subsection | Start | End | Funcitonal feature | Splicing information |
| Interactors from STRING. |
| Gene name | Interactors |
Related Drugs to HK1 |
| Drugs targeting this gene/protein. (DrugBank) |
| UniProt accession | Gene name | DrugBank ID | Drug name | Drug group | Actions |
| P19367 | HK1 | DB04395 | Phosphoaminophosphonic Acid-Adenylate Ester | experimental | |
| P19367 | HK1 | DB02007 | alpha-D-glucose 6-phosphate | experimental | |
| P19367 | HK1 | DB02379 | Beta-D-Glucose | experimental | |
| P19367 | HK1 | DB06266 | Lonidamine | investigational |
Related Diseases to HK1 |
| Previous studies relating to the alternative splicing of HK1 and disease information from the MeSH term (PubMed) |
| Gene | PMID | Title | Abstract | MeSH ID | MeSH term |
| HK1 | 19536174 | A mutation in an alternative untranslated exon of hexokinase 1 associated with hereditary motor and sensory neuropathy -- Russe (HMSNR). | Hereditary Motor and Sensory Neuropathy -- Russe (HMSNR) is a severe autosomal recessive disorder, identified in the Gypsy population. Our previous studies mapped the gene to 10q22-q23 and refined the gene region to approximately 70 kb. Here we report the comprehensive sequencing analysis and fine mapping of this region, reducing it to approximately 26 kb of fully characterised sequence spanning the upstream exons of Hexokinase 1 (HK1). We identified two sequence variants in complete linkage disequilibrium, a G>C in a novel alternative untranslated exon (AltT2) and a G>A in the adjacent intron, segregating with the disease in affected families and present in the heterozygote state in only 5/790 population controls. Sequence conservation of the AltT2 exon in 16 species with invariable preservation of the G allele at the mutated site, strongly favour the exonic change as the pathogenic mutation. Analysis of the Hk1 upstream region in mouse mRNA from testis and neural tissues showed an abundance of AltT2-containing transcripts generated by extensive, developmentally regulated alternative splicing. Expression is very low compared with ubiquitous Hk1 and all transcripts skip exon1, which encodes the protein domain responsible for binding to the outer mitochondrial membrane, and regulation of energy production and apoptosis. Hexokinase activity measurement and immunohistochemistry of the peripheral nerve showed no difference between patients and controls. The mutational mechanism and functional effects remain unknown and could involve disrupted translational regulation leading to increased anti-apoptotic activity (suggested by the profuse regenerative activity in affected nerves), or impairment of an unknown HK1 function in the peripheral nervous system (PNS). | D015417 | Hereditary Sensory and Motor Neuropathy |
Clinically important variants in HK1 |
| (ClinVar, 04/20/2024) |
| accession_id | uniprot_id | gene_name | Type | Variant | Clinical_significance |
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