General Information of Target

Target ID LDTP03760
Target Name Phosphoenolpyruvate carboxykinase, cytosolic [GTP] (PCK1)
Gene Name PCK1
Gene ID 5105
Synonyms
PEPCK1; Phosphoenolpyruvate carboxykinase, cytosolic [GTP]; PEPCK-C; EC 4.1.1.32; Serine-protein kinase PCK1; EC 2.7.11.-
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Sequence
MPPQLQNGLNLSAKVVQGSLDSLPQAVREFLENNAELCQPDHIHICDGSEEENGRLLGQM
EEEGILRRLKKYDNCWLALTDPRDVARIESKTVIVTQEQRDTVPIPKTGLSQLGRWMSEE
DFEKAFNARFPGCMKGRTMYVIPFSMGPLGSPLSKIGIELTDSPYVVASMRIMTRMGTPV
LEAVGDGEFVKCLHSVGCPLPLQKPLVNNWPCNPELTLIAHLPDRREIISFGSGYGGNSL
LGKKCFALRMASRLAKEEGWLAEHMLILGITNPEGEKKYLAAAFPSACGKTNLAMMNPSL
PGWKVECVGDDIAWMKFDAQGHLRAINPENGFFGVAPGTSVKTNPNAIKTIQKNTIFTNV
AETSDGGVYWEGIDEPLASGVTITSWKNKEWSSEDGEPCAHPNSRFCTPASQCPIIDAAW
ESPEGVPIEGIIFGGRRPAGVPLVYEALSWQHGVFVGAAMRSEATAAAEHKGKIIMHDPF
AMRPFFGYNFGKYLAHWLSMAQHPAAKLPKIFHVNWFRKDKEGKFLWPGFGENSRVLEWM
FNRIDGKASTKLTPIGYIPKEDALNLKGLGHINMMELFSISKEFWEKEVEDIEKYLEDQV
NADLPCEIEREILALKQRISQM
Target Bioclass
Enzyme
Family
Phosphoenolpyruvate carboxykinase [GTP] family
Subcellular location
Cytoplasm, cytosol
Function
Cytosolic phosphoenolpyruvate carboxykinase that catalyzes the reversible decarboxylation and phosphorylation of oxaloacetate (OAA) and acts as the rate-limiting enzyme in gluconeogenesis. Regulates cataplerosis and anaplerosis, the processes that control the levels of metabolic intermediates in the citric acid cycle. At low glucose levels, it catalyzes the cataplerotic conversion of oxaloacetate to phosphoenolpyruvate (PEP), the rate-limiting step in the metabolic pathway that produces glucose from lactate and other precursors derived from the citric acid cycle. At high glucose levels, it catalyzes the anaplerotic conversion of phosphoenolpyruvate to oxaloacetate. Acts as a regulator of formation and maintenance of memory CD8(+) T-cells: up-regulated in these cells, where it generates phosphoenolpyruvate, via gluconeogenesis. The resultant phosphoenolpyruvate flows to glycogen and pentose phosphate pathway, which is essential for memory CD8(+) T-cells homeostasis. In addition to the phosphoenolpyruvate carboxykinase activity, also acts as a protein kinase when phosphorylated at Ser-90: phosphorylation at Ser-90 by AKT1 reduces the binding affinity to oxaloacetate and promotes an atypical serine protein kinase activity using GTP as donor. The protein kinase activity regulates lipogenesis: upon phosphorylation at Ser-90, translocates to the endoplasmic reticulum and catalyzes phosphorylation of INSIG proteins (INSIG1 and INSIG2), thereby disrupting the interaction between INSIG proteins and SCAP and promoting nuclear translocation of SREBP proteins (SREBF1/SREBP1 or SREBF2/SREBP2) and subsequent transcription of downstream lipogenesis-related genes.
Uniprot ID
P35558
Ensemble ID
ENST00000319441.6
HGNC ID
HGNC:8724
ChEMBL ID
CHEMBL2911

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
A549 SNV: p.Q352K .
HEC1 SNV: p.L218I .
IGR37 SNV: p.V305A .
IGR39 SNV: p.V305A .
KMS27 SNV: p.A313S .
MOLT4 SNV: p.G546E .
NCIH2286 SNV: p.G302V .
NCIH2291 SNV: p.T382S .
NCIH23 SNV: p.P509H .
NCIH358 SNV: p.A251G .
NUGC3 SNV: p.E375D .
PEO1 SNV: p.K353E .
RL952 SNV: p.A78T .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 2 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
IPM
 Probe Info 
C288(0.00); C307(0.00)  LDD0241  [1]
DBIA
 Probe Info 
C288(1.34)  LDD3407  [2]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0022  KB02 A101D C288(2.23)  LDD2250  [2]
 LDCM0023  KB03 A101D C288(2.13)  LDD2667  [2]
 LDCM0024  KB05 RKO C288(1.34)  LDD3407  [2]

The Interaction Atlas With This Target

The Drug(s) Related To This Target

Approved
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Acyclovir Small molecular drug DB00787
Investigative
Click To Hide/Show 5 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Phosphoenolpyruvate Small molecular drug DB01819
1-(2-fluorobenzyl)-3-butyl-8-(N-acetyl-4-aminobenzyl)-xanthine . DB02008
1-allyl-3-butyl-8-(N-acetyl-4-aminobenzyl)-xanthine . DB03267
5'-guanylylmethylenebisphosphonate . DB03725
Mersalyl . DB09338

References

1 Oxidant-Induced Bioconjugation for Protein Labeling in Live Cells. ACS Chem Biol. 2023 Jan 20;18(1):112-122. doi: 10.1021/acschembio.2c00740. Epub 2022 Dec 21.
2 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840