Pck1
entrez
362282
canonical
uniprot
P07379
canonical
ensembl
ENSRNOG00000028616
resolver
ensembl
ENSRNOG00055000874
resolver
ensp
ENSRNOP00000030913
resolver
ensp
ENSRNOP00055001188
resolver
enst
ENSRNOT00055001468
resolver
genesymbol
Pck1
resolver
uniprot_entry
PCKGC_RAT
resolver
activity_regulation
ACTIVITY REGULATION: Phosphoenolpyruvate carboxykinase activity is regulated by acetylation and glucose levels (PubMed:30193097). The anaplerotic conversion of phosphoenolpyruvate to oxaloacetate is improved by PCK1 acetylation on Lys-91 (K91ac), Lys-473 (K473ac) and Lys-521 (K521ac) (PubMed:30193097). High glucose concentrations favor PCK1 anaplerotic activity by triggering acetylation on Lys-91 (K91ac). At low glucose levels, SIRT1-mediated deacetylation of Lys-91 promotes the cataplerotic conversion of oxaloacetate to phosphoenolpyruvate (By similarity). Phosphoenolpyruvate carboxykinase activity is inhibited by 3-mercaptopicolinate (PubMed:26322521). Phosphoenolpyruvate carboxykinase activity is inhibited by 3-[(carboxymethyl)thio]picolinate (CMP), which acts as a competitive inhibitor at the oxaloacetate/phosphoenolpyruvate-binding site (PubMed:31461616). Phosphorylation at Ser-90 reduces the binding affinity to oxaloacetate and converts the enzyme into an atypical protein kinase using GTP as donor (By similarity). {ECO:0000250|UniProtKB:P35558, ECO:0000269|PubMed:26322521, ECO:0000269|PubMed:30193097, ECO:0000269|PubMed:31461616}.
uniprot
proteins
amino_acid_sequence
MPPQLHNGLDFSAKVIQGSLDSLPQEVRKFVEGNAQLCQPEYIHICDGSEEEYGRLLAHMQEEGVIRKLKKYDNCWLALTDPRDVARIESKTVIITQEQRDTVPIPKSGQSQLGRWMSEEDFEKAFNARFPGCMKGRTMYVIPFSMGPLGSPLAKIGIELTDSPYVVASMRIMTRMGTSVLEALGDGEFIKCLHSVGCPLPLKKPLVNNWACNPELTLIAHLPDRREIISFGSGYGGNSLLGKKCFALRIASRLAKEEGWLAEHMLILGITNPEGKKKYLAAAFPSACGKTNLAMMNPTLPGWKVECVGDDIAWMKFDAQGNLRAINPENGFFGVAPGTSVKTNPNAIKTIQKNTIFTNVAETSDGGVYWEGIDEPLAPGVTITSWKNKEWRPQDEEPCAHPNSRFCTPASQCPIIDPAWESPEGVPIEGIIFGGRRPAGVPLVYEALSWQHGVFVGAAMRSEATAAAEHKGKVIMHDPFAMRPFFGYNFGKYLAHWLSMAHRPAAKLPKIFHVNWFRKDKNGKFLWPGFGENSRVLEWMFGRIEGEDSAKLTPIGYVPKEDALNLKGLGDVNVEELFGISKEFWEKEVEEIDKYLEDQVNADLPYEIERELRALKQRISQM
uniprot
proteins
ec_number
2.7.11.-
uniprot
proteins
ec_number
4.1.1.32
uniprot
proteins
function
FUNCTION: Cytosolic phosphoenolpyruvate carboxykinase that catalyzes the reversible decarboxylation and phosphorylation of oxaloacetate (OAA) and acts as the rate-limiting enzyme in gluconeogenesis (PubMed:26322521, PubMed:26709450, PubMed:28345895, PubMed:30193097, PubMed:31461616, PubMed:4186849). Regulates cataplerosis and anaplerosis, the processes that control the levels of metabolic intermediates in the citric acid cycle (PubMed:30193097). 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 (PubMed:30193097). At high glucose levels, it catalyzes the anaplerotic conversion of phosphoenolpyruvate to oxaloacetate (PubMed:30193097). Acts as a regulator of formation and maintenance of memory CD8(+) T-cells: up-regulated in these cells, where it generates phosphoenolpyruvate, via gluconeogenesis (By similarity). The resultant phosphoenolpyruvate flows to glycogen and pentose phosphate pathway, which is essential for memory CD8(+) T-cells homeostasis (By similarity). 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 (By similarity). 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 (By similarity). {ECO:0000250|UniProtKB:P35558, ECO:0000250|UniProtKB:Q9Z2V4, ECO:0000269|PubMed:26322521, ECO:0000269|PubMed:26709450, ECO:0000269|PubMed:28345895, ECO:0000269|PubMed:30193097, ECO:0000269|PubMed:31461616, ECO:0000269|PubMed:4186849}.
uniprot
proteins
mass_dalton
69416
uniprot
proteins
mutagenesis
MUTAGEN 89; /note="E->A,D,Q: Abolished phosphoenolpyruvate carboxykinase activity; decreased affinity for oxaloacetate."; /evidence="ECO:0000269|PubMed:26709450"; MUTAGEN 90; /note="S->A: Decreased phosphorylation and increased acetylation levels."; /evidence="ECO:0000269|PubMed:30193097"; MUTAGEN 91; /note="K->Q: 3-fold decrease of affinity for phosphoenolpyruvate."; /evidence="ECO:0000269|PubMed:30193097"; MUTAGEN 477; /note="H->R: Destabilization of the closed state of the omega-loop, resulting in decreased capture rates for the weaker binding substrates associated with catalysis in the phosphoenolpyruvate to oxaloacetate direction."; /evidence="ECO:0000269|PubMed:28345895
uniprot
proteins
pathway_participation
PATHWAY: Carbohydrate biosynthesis; gluconeogenesis. {ECO:0000269|PubMed:30193097}.
uniprot
proteins
post_translational_modification
PTM: Acetylated (PubMed:30193097). Lysine acetylation by p300/EP300 is increased on high glucose conditions and promotes ubiquitination by UBR5; acetylation is enhanced in the presence of BAG6. Deacetylated by SIRT2. Deacetylation of Lys-91 is carried out by SIRT1 and depends on PCK1 phosphorylation levels (By similarity). {ECO:0000250|UniProtKB:P35558, ECO:0000269|PubMed:30193097}.; PTM: Phosphorylated in a GSK3B-mediated pathway; phosphorylation affects the efficiency of SIRT1-mediated deacetylation, and regulates PCK1 ubiquitination and degradation (PubMed:30193097). Phosphorylation at Ser-90 by AKT1 reduces the binding affinity to oxaloacetate and promotes the protein kinase activity: phosphorylated PCK1 translocates to the endoplasmic reticulum, where it phosphorylates INSIG1 and INSIG2 (By similarity). {ECO:0000250|UniProtKB:P35558, ECO:0000269|PubMed:30193097}.; PTM: Ubiquitination by UBR5 leads to proteasomal degradation. {ECO:0000250|UniProtKB:P35558}.
uniprot
proteins
protein_family
Phosphoenolpyruvate carboxykinase [GTP] family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17685635
uniprot
proteins
pubmed
18197707
uniprot
proteins
pubmed
18335579
uniprot
proteins
pubmed
18772387
uniprot
proteins
pubmed
20476774
uniprot
proteins
pubmed
22673903
uniprot
proteins
pubmed
23127136
uniprot
proteins
pubmed
24863970
uniprot
proteins
pubmed
26322521
uniprot
proteins
pubmed
26709450
uniprot
proteins
pubmed
28345895
uniprot
proteins
pubmed
2909519
uniprot
proteins
pubmed
2993287
uniprot
proteins
pubmed
30193097
uniprot
proteins
pubmed
31461616
uniprot
proteins
pubmed
4186849
uniprot
proteins
pubmed
6096365
uniprot
proteins
sequence_length
622
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000305|PubMed:4186849}. Endoplasmic reticulum {ECO:0000250|UniProtKB:P35558}. Note=Phosphorylation at Ser-90 promotes translocation to the endoplasmic reticulum. {ECO:0000250|UniProtKB:P35558}.
uniprot
proteins