Gene/Proteome Database (LMPD)
LMPD ID
LMP000512
Gene ID
Species
Homo sapiens (Human)
Gene Name
pyruvate dehydrogenase kinase, isozyme 1
Gene Symbol
Synonyms
-
Chromosome
2
Map Location
2q31.1
EC Number
2.7.11.2
Summary
Pyruvate dehydrogenase (PDH) is a mitochondrial multienzyme complex that catalyzes the oxidative decarboxylation of pyruvate and is one of the major enzymes responsible for the regulation of homeostasis of carbohydrate fuels in mammals. The enzymatic activity is regulated by a phosphorylation/dephosphorylation cycle. Phosphorylation of PDH by a specific pyruvate dehydrogenase kinase (PDK) results in inactivation. Multiple alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Jun 2013]
Orthologs
Proteins
| [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial isoform 1 precursor | |
|---|---|
| Refseq ID | NP_001265478 |
| Protein GI | 514052656 |
| UniProt ID | Q15118 |
| mRNA ID | NM_001278549 |
| Length | 456 |
| RefSeq Status | REVIEWED |
| MRLARLLRGAALAGPGPGLRAAGFSRSFSSDSGSSPASERGVPGQVDFYARFSPSPLSMKQFLDFGSVNACEKTSFMFLRQELPVRLANIMKEISLLPDNLLRTPSVQLVQSWYIQSLQELLDFKDKSAEDAKAIYERPRRTWLQVSSLCCMACKMIFTDTVIRIRNRHNDVIPTMAQGVIEYKESFGVDPVTSQNVQYFLDRFYMSRISIRMLLNQHSLLFGGKGKGSPSHRKHIGSINPNCNVLEVIKDGYENARRLCDLYYINSPELELEELNAKSPGQPIQVVYVPSHLYHMVFELFKNAMRATMEHHANRGVYPPIQVHVTLGNEDLTVKMSDRGGGVPLRKIDRLFNYMYSTAPRPRVETSRAVPLAGFGYGLPISRLYAQYFQGDLKLYSLEGYGTDAVIYIKALSTDSIERLPVYNKAAWKHYNTNHEADDWCVPSREPKDMTTFRSA | |
| [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial isoform 2 precursor | |
|---|---|
| Refseq ID | NP_002601 |
| Protein GI | 4505689 |
| UniProt ID | Q15118 |
| mRNA ID | NM_002610 |
| Length | 436 |
| RefSeq Status | REVIEWED |
| MRLARLLRGAALAGPGPGLRAAGFSRSFSSDSGSSPASERGVPGQVDFYARFSPSPLSMKQFLDFGSVNACEKTSFMFLRQELPVRLANIMKEISLLPDNLLRTPSVQLVQSWYIQSLQELLDFKDKSAEDAKAIYDFTDTVIRIRNRHNDVIPTMAQGVIEYKESFGVDPVTSQNVQYFLDRFYMSRISIRMLLNQHSLLFGGKGKGSPSHRKHIGSINPNCNVLEVIKDGYENARRLCDLYYINSPELELEELNAKSPGQPIQVVYVPSHLYHMVFELFKNAMRATMEHHANRGVYPPIQVHVTLGNEDLTVKMSDRGGGVPLRKIDRLFNYMYSTAPRPRVETSRAVPLAGFGYGLPISRLYAQYFQGDLKLYSLEGYGTDAVIYIKALSTDSIERLPVYNKAAWKHYNTNHEADDWCVPSREPKDMTTFRSA | |
| transit_peptide: 1..28 calculated_mol_wt: 2870 peptide sequence: MRLARLLRGAALAGPGPGLRAAGFSRSF mat_peptide: 29..456 product: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial isoform 1 calculated_mol_wt: 48771 peptide sequence: SSDSGSSPASERGVPGQVDFYARFSPSPLSMKQFLDFGSVNACEKTSFMFLRQELPVRLANIMKEISLLPDNLLRTPSVQLVQSWYIQSLQELLDFKDKSAEDAKAIYERPRRTWLQVSSLCCMACKMIFTDTVIRIRNRHNDVIPTMAQGVIEYKESFGVDPVTSQNVQYFLDRFYMSRISIRMLLNQHSLLFGGKGKGSPSHRKHIGSINPNCNVLEVIKDGYENARRLCDLYYINSPELELEELNAKSPGQPIQVVYVPSHLYHMVFELFKNAMRATMEHHANRGVYPPIQVHVTLGNEDLTVKMSDRGGGVPLRKIDRLFNYMYSTAPRPRVETSRAVPLAGFGYGLPISRLYAQYFQGDLKLYSLEGYGTDAVIYIKALSTDSIERLPVYNKAAWKHYNTNHEADDWCVPSREPKDMTTFRSA transit_peptide: 1..28 inference: non-experimental evidence, no additional details recorded note: Mitochondrion (Potential); propagated from UniProtKB/Swiss-Prot (Q15118.1) calculated_mol_wt: 2870 peptide sequence: MRLARLLRGAALAGPGPGLRAAGFSRSF mat_peptide: 29..436 product: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial experiment: experimental evidence, no additional details recorded note: propagated from UniProtKB/Swiss-Prot (Q15118.1) calculated_mol_wt: 46392 peptide sequence: SSDSGSSPASERGVPGQVDFYARFSPSPLSMKQFLDFGSVNACEKTSFMFLRQELPVRLANIMKEISLLPDNLLRTPSVQLVQSWYIQSLQELLDFKDKSAEDAKAIYDFTDTVIRIRNRHNDVIPTMAQGVIEYKESFGVDPVTSQNVQYFLDRFYMSRISIRMLLNQHSLLFGGKGKGSPSHRKHIGSINPNCNVLEVIKDGYENARRLCDLYYINSPELELEELNAKSPGQPIQVVYVPSHLYHMVFELFKNAMRATMEHHANRGVYPPIQVHVTLGNEDLTVKMSDRGGGVPLRKIDRLFNYMYSTAPRPRVETSRAVPLAGFGYGLPISRLYAQYFQGDLKLYSLEGYGTDAVIYIKALSTDSIERLPVYNKAAWKHYNTNHEADDWCVPSREPKDMTTFRSA | |
Gene Information
Entrez Gene ID
Gene Name
pyruvate dehydrogenase kinase, isozyme 1
Gene Symbol
Species
Homo sapiens
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0005759 | TAS:Reactome | C | mitochondrial matrix |
| GO:0005739 | TAS:ProtInc | C | mitochondrion |
| GO:0005524 | IEA:UniProtKB-KW | F | ATP binding |
| GO:0004672 | IDA:UniProtKB | F | protein kinase activity |
| GO:0004674 | IEA:UniProtKB-KW | F | protein serine/threonine kinase activity |
| GO:0004740 | IDA:UniProtKB | F | pyruvate dehydrogenase (acetyl-transferring) kinase activity |
| GO:0008283 | IMP:UniProtKB | P | cell proliferation |
| GO:0044237 | TAS:Reactome | P | cellular metabolic process |
| GO:0006006 | TAS:ProtInc | P | glucose metabolic process |
| GO:0097411 | IMP:UniProtKB | P | hypoxia-inducible factor-1alpha signaling pathway |
| GO:0008631 | IMP:UniProtKB | P | intrinsic apoptotic signaling pathway in response to oxidative stress |
| GO:0006468 | IDA:GOC | P | protein phosphorylation |
| GO:0006090 | TAS:Reactome | P | pyruvate metabolic process |
| GO:0010510 | TAS:Reactome | P | regulation of acetyl-CoA biosynthetic process from pyruvate |
| GO:0010906 | IMP:UniProtKB | P | regulation of glucose metabolic process |
| GO:0044281 | TAS:Reactome | P | small molecule metabolic process |
KEGG Pathway Links
| KEGG Pathway ID | Description |
|---|---|
| hsa04066 | HIF-1 signaling pathway |
Domain Information
UniProt Annotations
Entry Information
Gene Name
pyruvate dehydrogenase kinase, isozyme 1
Protein Entry
Q15118_HUMAN
UniProt ID
Species
Human
Comments
| Comment Type | Description |
|---|---|
| Alternative Products | Event=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q15118-1; Sequence=Displayed; Name=2; IsoId=Q15118-2; Sequence=VSP_055172; |
| Catalytic Activity | ATP + [pyruvate dehydrogenase (acetyl- transferring)] = ADP + [pyruvate dehydrogenase (acetyl- transferring)] phosphate. {ECO |
| Enzyme Regulation | Activity is enhanced by binding to the pyruvate dehydrogenase subunit DLAT. Inhibited by AZD7545; this compound interferes with DLAT binding and thereby inhibits kinase activity. Inhibited by dichloroacetate and radicicol. |
| Function | Kinase that plays a key role in regulation of glucose and fatty acid metabolism and homeostasis via phosphorylation of the pyruvate dehydrogenase subunits PDHA1 and PDHA2. This inhibits pyruvate dehydrogenase activity, and thereby regulates metabolite flux through the tricarboxylic acid cycle, down-regulates aerobic respiration and inhibits the formation of acetyl-coenzyme A from pyruvate. Plays an important role in cellular responses to hypoxia and is important for cell proliferation under hypoxia. Protects cells against apoptosis in response to hypoxia and oxidative stress. {ECO |
| Induction | Up-regulated via the HIF1A signaling pathway in response to hypoxia. |
| Interaction | Q16513:PKN2; NbExp=6; IntAct=EBI-7016221, EBI-2511350; |
| Ptm | Phosphorylated by constitutively activated ABL1, FGFR1, FLT3 and JAK2 (in vitro), and this may also occur in cancer cells that express constitutively activated ABL1, FGFR1, FLT3 and JAK2. Phosphorylation at Tyr-243 and Tyr-244 strongly increases kinase activity, while phosphorylation at Tyr-136 has a lesser effect. |
| Similarity | Belongs to the PDK/BCKDK protein kinase family. |
| Similarity | Contains 1 histidine kinase domain. |
| Subcellular Location | Mitochondrion matrix . |
| Subunit | Homodimer, and heterodimer with PDK2. Interacts with the pyruvate dehydrogenase complex subunit DLAT, and is part of the multimeric pyruvate dehydrogenase complex that contains multiple copies of pyruvate dehydrogenase (E1), dihydrolipoamide acetyltransferase (DLAT, E2) and lipoamide dehydrogenase (DLD, E3). |
| Tissue Specificity | Expressed predominantly in the heart. Detected at lower levels in liver, skeletal muscle and pancreas. |
Identical and Related Proteins
Unique RefSeq proteins for LMP000512 (as displayed in Record Overview)
| Protein GI | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| 514052656 | RefSeq | NP_001265478 | 456 | [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial isoform 1 precursor |
| 4505689 | RefSeq | NP_002601 | 436 | [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial isoform 2 precursor |
Identical Sequences to LMP000512 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:4505689 | DBBJ | BAG35578.1 | 436 | unnamed protein product [Homo sapiens] |
| GI:4505689 | DBBJ | BAI46638.1 | 436 | pyruvate dehydrogenase kinase, isozyme 1, partial [synthetic construct] |
| GI:4505689 | GenBank | ABM87667.1 | 436 | pyruvate dehydrogenase kinase, isozyme 1, partial [synthetic construct] |
| GI:4505689 | GenBank | AHD74340.1 | 436 | Sequence 13706 from patent US 8586006 |
| GI:4505689 | GenBank | AIC49358.1 | 436 | PDK1, partial [synthetic construct] |
| GI:4505689 | GenBank | AIC62542.1 | 436 | PDK1, partial [synthetic construct] |
Related Sequences to LMP000512 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:514052656 | DBBJ | BAH14173.1 | 456 | unnamed protein product [Homo sapiens] |
| GI:4505689 | GenBank | AAX43259.1 | 437 | pyruvate dehydrogenase kinase isoenzyme 1, partial [synthetic construct] |
| GI:514052656 | GenBank | ABB29979.1 | 456 | mitochondrial pyruvate dehydrogenase kinase isoenzyme 1 [Homo sapiens] |
| GI:4505689 | GenBank | ABB29979.1 | 456 | mitochondrial pyruvate dehydrogenase kinase isoenzyme 1 [Homo sapiens] |
| GI:514052656 | RefSeq | XP_001147224.2 | 456 | PREDICTED: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial isoform X2 [Pan troglodytes] |
| GI:514052656 | RefSeq | XP_003824308.1 | 456 | PREDICTED: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial isoform X1 [Pan paniscus] |
| GI:514052656 | RefSeq | XP_004032848.1 | 489 | PREDICTED: [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 1, mitochondrial isoform 2 [Gorilla gorilla gorilla] |
| GI:4505689 | RefSeq | NP_001265478.1 | 456 | [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial isoform 1 precursor [Homo sapiens] |
| GI:4505689 | RefSeq | XP_005573542.1 | 436 | PREDICTED: [Pyruvate dehydrogenase [lipoamide]] kinase isozyme 1, mitochondrial isoform X1 [Macaca fascicularis] |
| GI:514052656 | RefSeq | XP_009442041.1 | 461 | PREDICTED: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial isoform X1 [Pan troglodytes] |
| GI:4505689 | RefSeq | XP_009442042.1 | 441 | PREDICTED: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial isoform X3 [Pan troglodytes] |
| GI:4505689 | RefSeq | XP_010375891.1 | 436 | PREDICTED: [Pyruvate dehydrogenase (acetyl-transferring)] kinase isozyme 1, mitochondrial [Rhinopithecus roxellana] |