Reactome | UniProt:P19367 HK1

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UniProt:P19367 HK1 Show undefined attributes

chain	chain:1-917
checksum	F29A6837531C0594
comment	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) (PubMed:1637300, PubMed:25316723, PubMed:27374331). Does not phosphorylate N-acetyl-D-glucosamine (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 (PubMed:27374331). 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(+)CATALYTIC ACTIVITY D-fructose + ATP = D-fructose 6-phosphate + ADP + H(+)CATALYTIC ACTIVITY D-glucose + ATP = D-glucose 6-phosphate + ADP + H(+)CATALYTIC ACTIVITY D-mannose + ATP = D-mannose 6-phosphate + ADP + H(+)CATALYTIC ACTIVITY D-glucosamine + ATP = D-glucosamine 6-phosphate + ADP + H(+)ACTIVITY REGULATION Hexokinase is an allosteric enzyme inhibited by its product D-glucose 6-phosphate (PubMed:1637300). Hexokinase activity is inhibited by N-acetyl-D-glucosamine (PubMed:27374331).PATHWAY Carbohydrate metabolism; hexose metabolism.PATHWAY Carbohydrate degradation; glycolysis; D-glyceraldehyde 3-phosphate and glycerone phosphate from D-glucose: step 1/4.SUBUNIT Monomer (PubMed:10686099). Interacts with RABL2/RABL2A; binds preferentially to GTP-bound RABL2 (By similarity). Interacts with VDAC1 (PubMed:22304920). The HK1-VDAC1 complex interacts with ATF2 (PubMed:22304920). Interacts (via N-terminal spermatogenic cell-specific region) with PFKM (via C-terminus) (By similarity). Interacts with SMAD5 (PubMed:28675158).INTERACTION The mitochondrial-binding peptide (MBP) region promotes association with the mitochondrial outer membrane (Probable). Dissociates from the mitochondrial outer membrane following inhibition by N-acetyl-D-glucosamine, leading to relocation to the cytosol (PubMed:27374331).ALTERNATIVE PRODUCTS Isoform 2: Erythrocyte specific (Ref.6). Isoform 3: Testis-specific (PubMed:10978502). Isoform 4: Testis-specific (PubMed:10978502).DOMAIN The N- and C-terminal halves of this hexokinase contain a hexokinase domain (PubMed:10574795, PubMed:9493266, PubMed:9735292). The catalytic activity is associated with the C-terminus while regulatory function is associated with the N-terminus (PubMed:10574795, PubMed:9493266, PubMed:9735292). Each domain can bind a single D-glucose and D-glucose 6-phosphate molecule (PubMed:9493266).DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the hexokinase family.CAUTION Hexokinase is known to act as a monomer (PubMed:10686099). It however homodimerizes at elevated protein concentrations used for crystallizations (PubMed:10574795, PubMed:9493266).ONLINE INFORMATION Hexokinase entry
crossReference	[DatabaseIdentifier:12221129] PDB:4F9O [DatabaseIdentifier:12341790] RefSeq:NP_277032.1 [DatabaseIdentifier:12341798] RefSeq:NP_001309293.1 [DatabaseIdentifier:12341796] RefSeq:XP_047281092.1 [DatabaseIdentifier:12341791] RefSeq:NP_277031.1 [DatabaseIdentifier:12341793] RefSeq:XP_054221663.1 [DatabaseIdentifier:12341795] RefSeq:NP_000179.2 [DatabaseIdentifier:12341792] RefSeq:XP_054221662.1 [DatabaseIdentifier:12341794] RefSeq:XP_024303737.1 [DatabaseIdentifier:12341797] RefSeq:XP_047281093.1 [DatabaseIdentifier:12341789] RefSeq:XP_054221661.1 [DatabaseIdentifier:12341787] RefSeq:NP_277035.2 [DatabaseIdentifier:12341786] RefSeq:NP_001345192.1 [DatabaseIdentifier:12341788] RefSeq:NP_277033.1 [DatabaseIdentifier:12291957] Pharos - Targets:P19367 [DatabaseIdentifier:12254097] PRO:P19367 [DatabaseIdentifier:12221136] PDB:1CZA [DatabaseIdentifier:12221137] PDB:1QHA [DatabaseIdentifier:12221135] PDB:4FPB [DatabaseIdentifier:12221132] PDB:1HKC [DatabaseIdentifier:12221134] PDB:4FPA [DatabaseIdentifier:12221131] PDB:4FOI [DatabaseIdentifier:12221133] PDB:1HKB [DatabaseIdentifier:11460713] ENSEMBL:ENSG00000156515 [DatabaseIdentifier:11553684] ENSEMBL:ENSP00000494664 [DatabaseIdentifier:11553685] ENSEMBL:ENSP00000415949 [DatabaseIdentifier:11553683] ENSEMBL:ENSP00000352398 [DatabaseIdentifier:11553682] ENSEMBL:ENSP00000298649 [DatabaseIdentifier:11676383] ENSEMBL:ENST00000298649 [DatabaseIdentifier:11676381] ENSEMBL:ENST00000643399 [DatabaseIdentifier:11676382] ENSEMBL:ENST00000436817 [DatabaseIdentifier:11676384] ENSEMBL:ENST00000359426 [DatabaseIdentifier:11794122] GeneCards:HK1 [DatabaseIdentifier:11810054] GlyGen:P19367 [DatabaseIdentifier:11830994] HMDB Protein:HMDBP00215 [DatabaseIdentifier:11847105] HPA:ENSG00000156515-HK1 [DatabaseIdentifier:12131773] OpenTargets:ENSG00000156515 [DatabaseIdentifier:12136033] Orphanet:HK1 [DatabaseIdentifier:12221130] PDB:4FOE [DatabaseIdentifier:12221128] PDB:1DGK
databaseName	UniProt
dbId	56894
description	recommendedName: fullName evidence="27"Hexokinase-1 ecNumber evidence="8"2.7.1.1 alternativeName: fullName evidence="25"Brain form hexokinase alternativeName: fullName evidence="26"Hexokinase type I shortName evidence="26"HK I alternativeName: fullName evidence="1"Hexokinase-A
displayName	UniProt:P19367 HK1
geneName	HK1
identifier	P19367
isSequenceChanged	false
keyword	3D-structure Acetylation Allosteric enzyme Alternative splicing ATP-binding Charcot-Marie-Tooth disease Cytoplasm Direct protein sequencing Disease variant Glycolysis Hereditary hemolytic anemia Immunity Inflammatory response Innate immunity Intellectual disability Kinase Membrane Mitochondrion Mitochondrion outer membrane Neurodegeneration Neuropathy Nucleotide-binding Phosphoprotein Proteomics identification Reference proteome Repeat Retinitis pigmentosa Transferase
modified	[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
moleculeType	Protein
name	HK1
otherIdentifier	11718291_a_at 11718292_s_at 11731491_a_at 11752103_a_at 16705577 200697_PM_at 200697_at 3098 3250279 3250280 3250281 3250282 3250284 3250285 3250288 3250289 3250290 3250294 3250295 3250296 3250297 3250298 3250302 3250303 3250304 3250307 3250308 3250309 3250310 3250311 3250312 3250313 3250314 3250323 3250324 3250325 3250326 3250327 3250329 3250331 3250341 3250342 3250343 3250344 3250346 3250347 3250348 3250349 3250350 3250351 3250352 3250353 3250354 3250355 3250356 3250357 3250359 3250360 3250361 47648_at 7928019 A_14_P123703 A_23_P217958 A_24_P367965 GE58076 GE60467 GO:0000166 GO:0001678 GO:0002376 GO:0002720 GO:0003824 GO:0004340 GO:0004396 GO:0005515 GO:0005524 GO:0005536 GO:0005737 GO:0005739 GO:0005741 GO:0005829 GO:0005975 GO:0006002 GO:0006006 GO:0006013 GO:0006091 GO:0006096 GO:0006954 GO:0008865 GO:0009298 GO:0016020 GO:0016301 GO:0016740 GO:0016773 GO:0019158 GO:0019318 GO:0019637 GO:0031966 GO:0032731 GO:0042834 GO:0045087 GO:0045121 GO:0046835 GO:0047931 GO:0051156 GO:0055086 GO:0061621 GO:0061728 GO:0072655 GO:0072656 GO:0098542 GO:1901135 HMNXSV003053862 ILMN_1755548 ILMN_1761829 ILMN_2382990 M75126_at PH_hs_0006537 TC10000419.hg TC10002109.hg U38227_s_at g4504390_3p_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-70395] HK1 [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5621861] HK1 L529S [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5621873] HK1 H577_C672del [cytosol] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-5621880] HK1 T680S [cytosol] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000156515] ENSEMBL:ENSG00000156515 HK1 [ReferenceDNASequence:12678635] UCSC:P19367 HK1 [ReferenceDNASequence:11325262] BioGPS Gene:3098 HK1 [ReferenceDNASequence:11391952] COSMIC - genes:HK1 HK1 [ReferenceDNASequence:11422794] CTD Gene:3098 HK1 [ReferenceDNASequence:11427680] dbSNP Gene:3098 HK1 [ReferenceDNASequence:11825817] HGNC:4922 HK1 [ReferenceDNASequence:11867689] KEGG:hsa:3098 HK1 [ReferenceDNASequence:11955051] Monarch:3098 HK1 [ReferenceDNASequence:12039144] NCBI Gene:3098 HK1 [ReferenceDNASequence:12116202] OMIM:142600 HK1
referenceTranscript	[ReferenceRNASequence:12523673] RefSeq:XM_054365687.1 HK1 [ReferenceRNASequence:12523677] RefSeq:NM_033497.3 HK1 [ReferenceRNASequence:12523667] RefSeq:NM_033500.2 HK1 [ReferenceRNASequence:12523670] RefSeq:XM_047425137.1 HK1 [ReferenceRNASequence:12523669] RefSeq:NM_001322364.2 HK1 [ReferenceRNASequence:12523674] RefSeq:NM_001358263.1 HK1 [ReferenceRNASequence:12523679] RefSeq:XM_024447969.2 HK1 [ReferenceRNASequence:12523676] RefSeq:NM_033498.3 HK1 [ReferenceRNASequence:12523675] RefSeq:XM_054365686.1 HK1 [ReferenceRNASequence:12523668] RefSeq:NM_000188.3 HK1 [ReferenceRNASequence:12523678] RefSeq:NM_033496.3 HK1 [ReferenceRNASequence:12523671] RefSeq:XM_047425136.1 HK1 [ReferenceRNASequence:12523672] RefSeq:XM_054365688.1 HK1
schemaClass	ReferenceGeneProduct
secondaryIdentifier	HXK1_HUMAN E9PCK0 O43443 O43444 O75574 Q5VTC3 Q96HC8 Q9NNZ4 Q9NNZ5
sequenceLength	917
species	[Species:48887] Homo sapiens
stId	uniprot:P19367
url	http://purl.uniprot.org/uniprot/P19367

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-70395] HK1 [cytosol] [EntityWithAccessionedSequence:R-HSA-5621861] HK1 L529S [cytosol] [EntityWithAccessionedSequence:R-HSA-5621873] HK1 H577_C672del [cytosol] [EntityWithAccessionedSequence:R-HSA-5621880] HK1 T680S [cytosol]
(referenceSequence)	[ReplacedResidue:5621841] L-leucine 529 replaced with L-serine [FragmentDeletionModification:5621917] Deletion of residues 577 to 672 [ReplacedResidue:5621842] L-threonine 680 replaced with L-serine
(interactor)	[UndirectedInteraction:11148599] UniProt:P13569 <-> UniProt:P19367 (IntAct) [UndirectedInteraction:11156453] UniProt:P05480 <-> UniProt:P19367 (IntAct) [UndirectedInteraction:11165251] UniProt:P19367 <-> UniProt:P15336 (IntAct) [UndirectedInteraction:11165253] UniProt:P19367 <-> UniProt:P21796 (IntAct) [UndirectedInteraction:11165255] UniProt:P19367 <-> UniProt:P19367 (IntAct) [UndirectedInteraction:11165255] UniProt:P19367 <-> UniProt:P19367 (IntAct) [UndirectedInteraction:11165257] UniProt:P19367 <-> UniProt:Q03135 (IntAct) [UndirectedInteraction:11165259] UniProt:P19367 <-> UniProt:P52790 (IntAct) [UndirectedInteraction:11165261] UniProt:P19367 <-> UniProt:P52789 (IntAct) [UndirectedInteraction:11165263] UniProt:P19367 <-> UniProt:Q2TB90 (IntAct) [UndirectedInteraction:11165265] UniProt:P19367 <-> UniProt:P12931 (IntAct) [UndirectedInteraction:11165267] UniProt:P19367 <-> UniProt:Q15388 (IntAct) [UndirectedInteraction:11165269] UniProt:P19367 <-> UniProt:P15056 (IntAct)