Molecule Information

General Information of the Molecule (ID: Mol04145)

• Name: Pyruvate kinase muscle isozyme 1 (PKM1) ,Homo sapiens
• Synonyms: Cytosolic thyroid hormone-binding protein; Opa-interacting protein 3; Pyruvate kinase 2/3; Pyruvate kinase muscle isozyme; Threonine-protein kinase PKM2; Thyroid hormone-binding protein 1; Tumor M2-PK; Tyrosine-protein kinase PKM2; p58
• Molecule Type: Protein
• Gene Name: PKM
• Gene ID: 5315
• Location: chr15:72199029-72231819[-]
• Sequence:
  MSKPHSEAGTAFIQTQQLHAAMADTFLEHMCRLDIDSPPITARNTGIICTIGPASRSVET
  LKEMIKSGMNVARLNFSHGTHEYHAETIKNVRTATESFASDPILYRPVAVALDTKGPEIR
  TGLIKGSGTAEVELKKGATLKITLDNAYMEKCDENILWLDYKNICKVVEVGSKIYVDDGL
  ISLQVKQKGADFLVTEVENGGSLGSKKGVNLPGAAVDLPAVSEKDIQDLKFGVEQDVDMV
  FASFIRKASDVHEVRKVLGEKGKNIKIISKIENHEGVRRFDEILEASDGIMVARGDLGIE
  IPAEKVFLAQKMMIGRCNRAGKPVICATQMLESMIKKPRPTRAEGSDVANAVLDGADCIM
  LSGETAKGDYPLEAVRMQHLIAREAEAAIYHLQLFEELRRLAPITSDPTEATAVGAVEAS
  FKCCSGAIIVLTKSGRSAHQVARYRPRAPIIAVTRNPQTARQAHLYRGIFPVLCKDPVQE
  AWAEDVDLRVNFAMNVGKARGFFKKGDVVIVLTGWRPGSGFTNTMRVVPVP
• 3D-structure: PDB ID: 1T5A; Classification: Transferase; Method: X-ray diffraction; Resolution: 2.80 Å
• Function: Catalyzes the final rate-limiting step of glycolysis by mediating the transfer of a phosphoryl group from phosphoenolpyruvate (PEP) to ADP, generating ATP (PubMed:15996096, PubMed:1854723, PubMed:20847263). The ratio between the highly active tetrameric form and nearly inactive dimeric form determines whether glucose carbons are channeled to biosynthetic processes or used for glycolytic ATP production (PubMed:15996096, PubMed:1854723, PubMed:20847263). The transition between the 2 forms contributes to the control of glycolysis and is important for tumor cell proliferation and survival (PubMed:15996096, PubMed:1854723, PubMed:20847263). .; [Isoform M2]: Isoform specifically expressed during embryogenesis that has low pyruvate kinase activity by itself and requires allosteric activation by D-fructose 1,6-bisphosphate (FBP) for pyruvate kinase activity (PubMed:18337823, PubMed:20847263). In addition to its pyruvate kinase activity in the cytoplasm, also acts as a regulator of transcription in the nucleus by acting as a protein kinase (PubMed:18191611, PubMed:21620138, PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661). Translocates into the nucleus in response to various signals, such as EGF receptor activation, and homodimerizes, leading to its conversion into a protein threonine- and tyrosine-protein kinase (PubMed:22056988, PubMed:22306293, PubMed:22901803, PubMed:24120661, PubMed:26787900). Catalyzes phosphorylation of STAT3 at 'Tyr-705' and histone H3 at 'Thr- 11' (H3T11ph), leading to activate transcription (PubMed:22306293, PubMed:22901803, PubMed:24120661). Its ability to activate transcription plays a role in cancer cells by promoting cell proliferation and promote tumorigenesis (PubMed:18337823, PubMed:22901803, PubMed:26787900). Promotes the expression of the immune checkpoint protein CD274 in BMAL1-deficient macrophages (By similarity). May also act as a translation regulator for a subset of mRNAs, independently of its pyruvate kinase activity: associates with subpools of endoplasmic reticulum-associated ribosomes, binds directly to the mRNAs translated at the endoplasmic reticulum and promotes translation of these endoplasmic reticulum-destined mRNAs (By similarity). Plays a role in caspase independent cell death of tumor cells (PubMed:17308100). .; [Isoform M1]: Pyruvate kinase isoform expressed in adult tissues, which replaces isoform M2 after birth (PubMed:18337823). In contrast to isoform M2, has high pyruvate kinase activity by itself and does not require allosteric activation by D-fructose 1,6-bisphosphate (FBP) for activity (PubMed:20847263). .
• Uniprot ID: KPYM_HUMAN
• Ensembl ID: ENSG00000067225
• HGNC ID: HGNC:9021

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 4 drug(s) in total

Daunorubicin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Chronic myeloid leukemia [ICD-11: 2A20.0] [1]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Chronic myeloid leukemia [ICD-11: 2A20.0]
• Resistant Drug: Daunorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: K562/ADMR cells; Blood; Homo sapiens (Human); CVCL_5950
• Experiment for Molecule Alteration: Expression profiles
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: The overexpression of PKM1 resulted in resistance of the parental cells to 5-FU and oxaliplatin.

Docetaxel

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Prostate cancer [ICD-11: 2C82.0] [1]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Resistant Drug: Docetaxel
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: PC-3/PTXR cells; Prostate; Homo sapiens (Human); CVCL_0035
• Experiment for Molecule Alteration: Expression profiles
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: The overexpression of PKM1 resulted in resistance of the parental cells to 5-FU and oxaliplatin.

Fluorouracil

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Gastric adenocarcinoma [ICD-11: 2B72.0] [1]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Resistant Drug: Fluorouracil
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MKN45 cells; Liver; Homo sapiens (Human); CVCL_0434
• In Vitro Model: MKN-45/F2R cells; Stomach; Homo sapiens (Human); CVCL_0434
• In Vitro Model: NUGC3 cells; Gastric; Homo sapiens (Human); CVCL_1612
• In Vitro Model: NUGC-3/5-FUR cells; Stomach; Homo sapiens (Human); CVCL_1612
• Experiment for Molecule Alteration: Expression profiles
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: The overexpression of PKM1 resulted in resistance of the parental cells to 5-FU and oxaliplatin.

Disease Class: Colon cancer [ICD-11: 2B90.1] [1]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Colon cancer [ICD-11: 2B90.1]
• Resistant Drug: Fluorouracil
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: DLD-1 cells; Colon; Homo sapiens (Human); CVCL_0248
• In Vitro Model: DLD-1/5-FUR cells; Colon; Homo sapiens (Human); CVCL_0248
• In Vitro Model: HT-29 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vitro Model: HT-29/5-FUR cells; Colon; Homo sapiens (Human); CVCL_0320
• Experiment for Molecule Alteration: Expression profiles
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: The overexpression of PKM1 resulted in resistance of the parental cells to 5-FU and oxaliplatin.

Disease Class: Prostate cancer [ICD-11: 2C82.0] [1]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Resistant Drug: Fluorouracil
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: PC-3 cells; Bone; Homo sapiens (Human); CVCL_0035
• Experiment for Molecule Alteration: Expression profiles
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: The overexpression of PKM1 resulted in resistance of the parental cells to 5-FU and oxaliplatin.

Disease Class: Chronic myeloid leukemia [ICD-11: 2A20.0] [1]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Chronic myeloid leukemia [ICD-11: 2A20.0]
• Resistant Drug: Fluorouracil
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: DLD-1 cells; Colon; Homo sapiens (Human); CVCL_0248
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• Experiment for Molecule Alteration: Expression profiles
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: The overexpression of PKM1 resulted in resistance of the parental cells to 5-FU and oxaliplatin.

Oxaliplatin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Gastric adenocarcinoma [ICD-11: 2B72.0] [1]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Gastric adenocarcinoma [ICD-11: 2B72.0]
• Resistant Drug: Oxaliplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: MKN45 cells; Liver; Homo sapiens (Human); CVCL_0434
• In Vitro Model: NUGC3 cells; Gastric; Homo sapiens (Human); CVCL_1612
• Experiment for Molecule Alteration: Expression profiles
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: The overexpression of PKM1 resulted in resistance of the parental cells to 5-FU and oxaliplatin.

Disease Class: Colon cancer [ICD-11: 2B90.1] [1]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Colon cancer [ICD-11: 2B90.1]
• Resistant Drug: Oxaliplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: DLD-1 cells; Colon; Homo sapiens (Human); CVCL_0248
• In Vitro Model: HT-29 cells; Colon; Homo sapiens (Human); CVCL_0320
• Experiment for Molecule Alteration: Expression profiles
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: The overexpression of PKM1 resulted in resistance of the parental cells to 5-FU and oxaliplatin.

Disease Class: Prostate cancer [ICD-11: 2C82.0] [1]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Prostate cancer [ICD-11: 2C82.0]
• Resistant Drug: Oxaliplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: PC-3 cells; Bone; Homo sapiens (Human); CVCL_0035
• Experiment for Molecule Alteration: Expression profiles
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: The overexpression of PKM1 resulted in resistance of the parental cells to 5-FU and oxaliplatin.

Disease Class: Chronic myeloid leukemia [ICD-11: 2A20.0] [1]

• Metabolic Type: Mitochondrial metabolism
• Resistant Disease: Chronic myeloid leukemia [ICD-11: 2A20.0]
• Resistant Drug: Oxaliplatin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: DLD-1 cells; Colon; Homo sapiens (Human); CVCL_0248
• In Vitro Model: DLD-1/OxR cells; Blood; Homo sapiens (Human); CVCL_0248
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• Experiment for Molecule Alteration: Expression profiles
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: The overexpression of PKM1 resulted in resistance of the parental cells to 5-FU and oxaliplatin.

References

• Ref 1: PKM1 is involved in resistance to anti-cancer drugs. Biochem Biophys Res Commun. 2016 Apr 22;473(1):174-180.