Phosphoenolpyruvate carboxykinase, cytosolic [GTP]
Details
- Name
- Phosphoenolpyruvate carboxykinase, cytosolic [GTP]
- Kind
- protein
- Synonyms
- 4.1.1.32
- PEPCK-C
- PEPCK1
- Serine-protein kinase PCK1
- Gene Name
- PCK1
- UniProtKB Entry
- P35558Swiss-Prot
- Organism
- Humans
- NCBI Taxonomy ID
- 9606
- Amino acid sequence
>lcl|BSEQ0001805|Phosphoenolpyruvate carboxykinase, cytosolic [GTP] MPPQLQNGLNLSAKVVQGSLDSLPQAVREFLENNAELCQPDHIHICDGSEEENGRLLGQM EEEGILRRLKKYDNCWLALTDPRDVARIESKTVIVTQEQRDTVPIPKTGLSQLGRWMSEE DFEKAFNARFPGCMKGRTMYVIPFSMGPLGSPLSKIGIELTDSPYVVASMRIMTRMGTPV LEAVGDGEFVKCLHSVGCPLPLQKPLVNNWPCNPELTLIAHLPDRREIISFGSGYGGNSL LGKKCFALRMASRLAKEEGWLAEHMLILGITNPEGEKKYLAAAFPSACGKTNLAMMNPSL PGWKVECVGDDIAWMKFDAQGHLRAINPENGFFGVAPGTSVKTNPNAIKTIQKNTIFTNV AETSDGGVYWEGIDEPLASGVTITSWKNKEWSSEDGEPCAHPNSRFCTPASQCPIIDAAW ESPEGVPIEGIIFGGRRPAGVPLVYEALSWQHGVFVGAAMRSEATAAAEHKGKIIMHDPF AMRPFFGYNFGKYLAHWLSMAQHPAAKLPKIFHVNWFRKDKEGKFLWPGFGENSRVLEWM FNRIDGKASTKLTPIGYIPKEDALNLKGLGHINMMELFSISKEFWEKEVEDIEKYLEDQV NADLPCEIEREILALKQRISQM
- Number of residues
- 622
- Molecular Weight
- 69193.975
- Theoretical pI
- 6.05
- GO Classification
- Functionsprotein serine kinase activity (using GTP as donor)Processescellular hyperosmotic salinity response / cellular hypotonic salinity response / cellular response to cAMP / cellular response to dexamethasone stimulus / cellular response to fructose stimulus / cellular response to glucagon stimulus / cellular response to glucose stimulus / cellular response to hypoxia / cellular response to insulin stimulus / cellular response to interleukin-1 / cellular response to phorbol 13-acetate 12-myristate / cellular response to raffinose / cellular response to retinoic acid / cellular response to tumor necrosis factor / glyceraldehyde-3-phosphate biosynthetic process / hepatocyte differentiation / peptidyl-serine phosphorylation / positive regulation of lipid biosynthetic process / positive regulation of memory T cell differentiation / positive regulation of transcription by RNA polymerase II / propionate catabolic process / regulation of lipid biosynthetic process / response to interleukin-6 / response to lipopolysaccharide / response to methionine / response to starvation / tricarboxylic acid metabolic processComponentsendoplasmic reticulum
- General Function
- Cytosolic phosphoenolpyruvate carboxykinase that catalyzes the reversible decarboxylation and phosphorylation of oxaloacetate (OAA) and acts as the rate-limiting enzyme in gluconeogenesis (PubMed:24863970, PubMed:26971250, PubMed:28216384, PubMed:30193097). Regulates cataplerosis and anaplerosis, the processes that control the levels of metabolic intermediates in the citric acid cycle (PubMed:24863970, PubMed:26971250, PubMed:28216384, 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 (PubMed:32322062). 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 (PubMed:32322062)
- Specific Function
- carboxylic acid binding
- Pfam Domain Function
- Signal Regions
- Not Available
- Transmembrane Regions
- Not Available
- Cellular Location
- Cytoplasm, cytosol
- Gene sequence
>lcl|BSEQ0016245|Phosphoenolpyruvate carboxykinase, cytosolic [GTP] (PCK1) ATGCCTCCTCAGCTGCAAAACGGCCTGAACCTCTCGGCCAAAGTTGTCCAGGGAAGCCTG GACAGCCTACCCCAGGCAGTGAGGGAGTTTCTCGAGAATAACGCTGAGCTGTGTCAGCCT GATCACATCCACATCTGTGACGGCTCTGAGGAGGAGAATGGGCGGCTTCTGGGCCAGATG GAGGAAGAGGGCATCCTCAGGCGGCTGAAGAAGTATGACAACTGCTGGTTGGCTCTCACT GACCCCAGGGATGTGGCCAGGATCGAAAGCAAGACGGTTATCGTCACCCAAGAGCAAAGA GACACAGTGCCCATCCCCAAAACAGGCCTCAGCCAGCTCGGTCGCTGGATGTCAGAGGAG GATTTTGAGAAAGCGTTCAATGCCAGGTTCCCAGGGTGCATGAAAGGTCGCACCATGTAC GTCATCCCATTCAGCATGGGGCCGCTGGGCTCGCCTCTGTCAAAGATCGGCATCGAGCTG ACGGATTCACCCTACGTGGTGGCCAGCATGCGGATCATGACGCGGATGGGCACGCCCGTC CTGGAAGCAGTGGGCGATGGGGAGTTTGTCAAATGCCTCCATTCTGTGGGGTGCCCTCTG CCTTTACAAAAGCCTTTGGTCAACAACTGGCCCTGCAACCCGGAGCTGACGCTCATCGCC CACCTGCCTGACCGCAGAGAGATCATCTCCTTTGGCAGTGGGTACGGCGGGAACTCGCTG CTCGGGAAGAAGTGCTTTGCTCTCAGGATGGCCAGCCGGCTGGCCAAGGAGGAAGGGTGG CTGGCAGAGCACATGCTGATTCTGGGTATAACCAACCCTGAGGGTGAGAAGAAGTACCTG GCGGCCGCATTTCCCAGCGCCTGCGGGAAGACCAACCTGGCCATGATGAACCCCAGCCTC CCCGGGTGGAAGGTTGAGTGCGTCGGGGATGACATTGCCTGGATGAAGTTTGACGCACAA GGTCATTTAAGGGCCATCAACCCAGAAAATGGCTTTTTCGGTGTCGCTCCTGGGACTTCA GTGAAGACCAACCCCAATGCCATCAAGACCATCCAGAAGAACACAATCTTTACCAATGTG GCCGAGACCAGCGACGGGGGCGTTTACTGGGAAGGCATTGATGAGCCGCTAGCTTCAGGT GTCACCATCACGTCCTGGAAGAATAAGGAGTGGAGCTCAGAGGATGGGGAACCTTGTGCC CACCCCAACTCGAGGTTCTGCACCCCTGCCAGCCAGTGCCCCATCATTGATGCTGCCTGG GAGTCTCCGGAAGGTGTTCCCATTGAAGGCATTATCTTTGGAGGCCGTAGACCTGCTGGT GTCCCTCTAGTCTATGAAGCTCTCAGCTGGCAACATGGAGTCTTTGTGGGGGCGGCCATG AGATCAGAGGCCACAGCGGCTGCAGAACATAAAGGCAAAATCATCATGCATGACCCCTTT GCCATGCGGCCCTTCTTTGGCTACAACTTCGGCAAATACCTGGCCCACTGGCTTAGCATG GCCCAGCACCCAGCAGCCAAACTGCCCAAGATCTTCCATGTCAACTGGTTCCGGAAGGAC AAGGAAGGCAAATTCCTCTGGCCAGGCTTTGGAGAGAACTCCAGGGTGCTGGAGTGGATG TTCAACCGGATCGATGGAAAAGCCAGCACCAAGCTCACGCCCATAGGCTACATCCCCAAG GAGGATGCCCTGAACCTGAAAGGCCTGGGGCACATCAACATGATGGAGCTTTTCAGCATC TCCAAGGAATTCTGGGAGAAGGAGGTGGAAGACATCGAGAAGTATCTGGAGGATCAAGTC AATGCCGACCTCCCCTGTGAAATCGAGAGAGAGATCCTTGCCTTGAAGCAAAGAATAAGC CAGATGTAA
- Chromosome Location
- 20
- Locus
- 20q13.31
- External Identifiers
Resource Link UniProtKB ID P35558 UniProtKB Entry Name PCKGC_HUMAN GenBank Protein ID 189945 GenBank Gene ID L05144 GeneCard ID PCK1 GenAtlas ID PCK1 HGNC ID HGNC:8724 PDB ID(s) 1KHB, 1KHE, 1KHF, 1KHG, 1M51, 1NHX, 2GMV KEGG ID hsa:5105 NCBI Gene ID 5105 - General References
- Stoffel M, Xiang KS, Espinosa R 3rd, Cox NJ, Le Beau MM, Bell GI: cDNA sequence and localization of polymorphic human cytosolic phosphoenolpyruvate carboxykinase gene (PCK1) to chromosome 20, band q13.31: PCK1 is not tightly linked to maturity-onset diabetes of the young. Hum Mol Genet. 1993 Jan;2(1):1-4. [Article]
- Ting CN, Burgess DL, Chamberlain JS, Keith TP, Falls K, Meisler MH: Phosphoenolpyruvate carboxykinase (GTP): characterization of the human PCK1 gene and localization distal to MODY on chromosome 20. Genomics. 1993 Jun;16(3):698-706. [Article]
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- Foley LH, Wang P, Dunten P, Ramsey G, Gubler ML, Wertheimer SJ: X-ray structures of two xanthine inhibitors bound to PEPCK and N-3 modifications of substituted 1,8-dibenzylxanthines. Bioorg Med Chem Lett. 2003 Nov 3;13(21):3871-4. [Article]
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Associated Data
- Drug Relations
Drug Drug group Pharmacological action? Type Actions Details Phosphoenolpyruvate experimental unknown target Details 1-(2-Fluorobenzyl)-3-Butyl-8-(N-Acetyl-4-Aminobenzyl)-Xanthine experimental unknown target Details 1-Allyl-3-Butyl-8-(N-Acetyl-4-Aminobenzyl)-Xanthine experimental unknown target Details 5'-Guanylylmethylenebisphosphonate experimental unknown target Details Mersalyl experimental unknown enzyme inhibitor Details