Pck1
entrez
18534
canonical
uniprot
Q9Z2V4
canonical
ensembl
ENSMUSG00000027513
resolver
ensp
ENSMUSP00000029017
resolver
enst
ENSMUST00000029017
resolver
genesymbol
Pck1
resolver
genesymbol_syn
Pepck
resolver
uniprot
Q3UEH3
resolver
uniprot_entry
PCKGC_MOUSE
resolver
uniprot_sec
Q3UEH3
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) (By similarity). 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). 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:P07379, ECO:0000250|UniProtKB:P35558, ECO:0000269|PubMed:30193097}.
uniprot
proteins
amino_acid_sequence
MPPQLHNGLDFSAKVIQGSLDSLPQAVRKFVEGNAQLCQPEYIHICDGSEEEYGQLLAHMQEEGVIRKLKKYDNCWLALTDPRDVARIESKTVIITQEQRDTVPIPKTGLSQLGRWMSEEDFEKAFNARFPGCMKGRTMYVIPFSMGPLGSPLAKIGIELTDSPYVVASMRIMTRMGISVLEALGDGEFIKCLHSVGCPLPLKKPLVNNWACNPELTLIAHLPDRREIISFGSGYGGNSLLGKKCFALRIASRLAKEEGWLAEHMLILGITNPEGKKKYLAAAFPSACGKTNLAMMNPSLPGWKVECVGDDIAWMKFDAQGNLRAINPENGFFGVAPGTSVKTNPNAIKTIQKNTIFTNVAETSDGGVYWEGIDEPLAPGVTITSWKNKEWRPQDAEPCAHPNSRFCTPASQCPIIDPAWESPEGVPIEGIIFGGRRPEGVPLVYEALSWQHGVFVGAAMRSEATAAAEHKGKIIMHDPFAMRPFFGYNFGKYLAHWLSMAHRPAAKLPKIFHVNWFRKDKDGKFLWPGFGENSRVLEWMFGRIEGEDSAKLTPIGYIPKENALNLKGLGGVNVEELFGISKEFWEKEVEEIDRYLEDQVNTDLPYEIERELRALKQRISQM
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:11792850, PubMed:11916968, PubMed:29230018, PubMed:30193097). 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 (PubMed:29230018). The resultant phosphoenolpyruvate flows to glycogen and pentose phosphate pathway, which is essential for memory CD8(+) T-cells homeostasis (PubMed:29230018). 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:0000269|PubMed:11792850, ECO:0000269|PubMed:11916968, ECO:0000269|PubMed:29230018, ECO:0000269|PubMed:30193097}.
uniprot
proteins
mass_dalton
69355
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 (By similarity). Deacetylated by SIRT1 (PubMed:30193097). {ECO:0000250|UniProtKB:P35558, ECO:0000269|PubMed:30193097}.; PTM: Ubiquitination by UBR5 leads to proteasomal degradation. {ECO:0000250|UniProtKB:P35558}.; PTM: Phosphorylated in a GSK3B-mediated pathway; phosphorylation affects the efficiency of SIRT1-mediated deacetylation, and regulates PCK1 ubiquitination and degradation. 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. {ECO:0000250|UniProtKB:P35558}.
uniprot
proteins
protein_family
Phosphoenolpyruvate carboxykinase [GTP] family
uniprot
proteins
pubmed
10221772
uniprot
proteins
pubmed
10938127
uniprot
proteins
pubmed
11792850
uniprot
proteins
pubmed
11916968
uniprot
proteins
pubmed
16100117
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
29230018
uniprot
proteins
pubmed
30193097
uniprot
proteins
sequence_length
622
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250|UniProtKB:P35558}. Endoplasmic reticulum {ECO:0000250|UniProtKB:P35558}. Note=Phosphorylation at Ser-90 promotes translocation to the endoplasmic reticulum. {ECO:0000250|UniProtKB:P35558}.
uniprot
proteins