Search Results

Overview

Uniprot ID	P35558
Protein Name	Phosphoenolpyruvate carboxykinase, cytosolic [GTP]
Gene Name	PCK1
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
471	ATAAAEHKGKIIMHD
473	AAAEHKGKIIMHDPF
91	DVARIESKTVIVTQE

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)

Protein Sequence

10 MPPQLQNGLN 20 LSAKVVQGSL 30 DSLPQAVREF 40 LENNAELCQP 50 DHIHICDGSE 60 EENGRLLGQM 70 EEEGILRRLK 80 KYDNCWLALT 90 DPRDVARIES 100 KTVIVTQEQR 110 DTVPIPKTGL 120 SQLGRWMSEE 130 DFEKAFNARF 140 PGCMKGRTMY 150 VIPFSMGPLG 160 SPLSKIGIEL 170 TDSPYVVASM 180 RIMTRMGTPV 190 LEAVGDGEFV 200 KCLHSVGCPL 210 PLQKPLVNNW 220 PCNPELTLIA 230 HLPDRREIIS 240 FGSGYGGNSL 250 LGKKCFALRM 260 ASRLAKEEGW 270 LAEHMLILGI 280 TNPEGEKKYL 290 AAAFPSACGK 300 TNLAMMNPSL 310 PGWKVECVGD 320 DIAWMKFDAQ 330 GHLRAINPEN 340 GFFGVAPGTS 350 VKTNPNAIKT 360 IQKNTIFTNV 370 AETSDGGVYW 380 EGIDEPLASG 390 VTITSWKNKE 400 WSSEDGEPCA 410 HPNSRFCTPA 420 SQCPIIDAAW 430 ESPEGVPIEG 440 IIFGGRRPAG 450 VPLVYEALSW 460 QHGVFVGAAM 470 RSEATAAAEH 480 KGKIIMHDPF 490 AMRPFFGYNF 500 GKYLAHWLSM 510 AQHPAAKLPK 520 IFHVNWFRKD 530 KEGKFLWPGF 540 GENSRVLEWM 550 FNRIDGKAST 560 KLTPIGYIPK 570 EDALNLKGLG 580 HINMMELFSI 590 SKEFWEKEVE 600 DIEKYLEDQV 610 NADLPCEIER 620 EILALKQRIS QM

Gene Ontology

Classification	GO ID	Description
Cellular Component	GO:0005737	cytoplasm
Cellular Component	GO:0005829	cytosol
Cellular Component	GO:0005783	endoplasmic reticulum
Cellular Component	GO:0070062	extracellular exosome
Cellular Component	GO:0005739	mitochondrion
Molecular Function	GO:0031406	carboxylic acid binding
Molecular Function	GO:0005525	GTP binding
Molecular Function	GO:0000287	magnesium ion binding
Molecular Function	GO:0030145	manganese ion binding
Molecular Function	GO:0004613	phosphoenolpyruvate carboxykinase (GTP) activity
Molecular Function	GO:0106264	protein serine kinase activity (using GTP as donor)
Biological Process	GO:0071549	cellular response to dexamethasone stimulus
Biological Process	GO:0071333	cellular response to glucose stimulus
Biological Process	GO:0032869	cellular response to insulin stimulus
Biological Process	GO:0006094	gluconeogenesis
Biological Process	GO:0042593	glucose homeostasis
Biological Process	GO:0006006	glucose metabolic process
Biological Process	GO:0046166	glyceraldehyde-3-phosphate biosynthetic process
Biological Process	GO:0046327	glycerol biosynthetic process from pyruvate
Biological Process	GO:0070365	hepatocyte differentiation
Biological Process	GO:0006107	oxaloacetate metabolic process
Biological Process	GO:0018105	peptidyl-serine phosphorylation
Biological Process	GO:0046889	positive regulation of lipid biosynthetic process
Biological Process	GO:0043382	positive regulation of memory T cell differentiation
Biological Process	GO:0046890	regulation of lipid biosynthetic process
Biological Process	GO:0032868	response to insulin
Biological Process	GO:0042594	response to starvation
Biological Process	GO:0072350	tricarboxylic acid metabolic process

Reference

[1] Yang Z, Yan C, Ma J, Peng P, Ren X et al.. Lactylome analysis suggests lactylation-dependent mechanisms of metabolic adaptation in hepatocellular carcinoma.. Nat Metab 5(1):61-79. 2023 Jan. PMID: 36593272.

[2] Hong H, Chen X, Wang H, Gu X, Yuan Y et al.. Global profiling of protein lysine lactylation and potential target modified protein analysis in hepatocellular carcinoma.. Proteomics 23(9):e2200432. 2023 May. PMID: 36625413.