Search Results

Overview

Uniprot IDQ01167
Protein NameForkhead box protein K2
Gene NameFOXK2
OrganismHomo sapiens

Kla Sites from experimental identification

Position Flanking peptide
161 FTALSSEKREKQEAS
223 GAGSSGYKVGRVMPS
300 PYYRTADKGWQNSIR
328 RSQEEPGKGSFWRID
527 DHREVKVKVEPIPAI
630 QPEQPELKRIKTEDG

Function

Transcriptional regulator involved in different processes such as glucose metabolism, aerobic glycolysis and autophagy (PubMed:38735474). Recognizes and binds the forkhead DNA sequence motif (5'-GTAAACA-3') and can both act as a transcription activator or repressor, depending on the context (PubMed:22083952, PubMed:25451922). Together with FOXK1, acts as a key regulator of metabolic reprogramming towards aerobic glycolysis, a process in which glucose is converted to lactate in the presence of oxygen (By similarity). Acts by promoting expression of enzymes for glycolysis (such as hexokinase-2 (HK2), phosphofructokinase, pyruvate kinase (PKLR) and lactate dehydrogenase), while suppressing further oxidation of pyruvate in the mitochondria by up-regulating pyruvate dehydrogenase kinases PDK1 and PDK4 (By similarity). Probably plays a role in gluconeogenesis during overnight fasting, when lactate from white adipose tissue and muscle is the main substrate (By similarity). Together with FOXK1, acts as a negative regulator of autophagy in skeletal muscle: in response to starvation, enters the nucleus, binds the promoters of autophagy genes and represses their expression, preventing proteolysis of skeletal muscle proteins (By similarity). In addition to the 5'-GTAAACA-3' DNA motif, also binds the 5'-TGANTCA-3' palindromic DNA motif, and co-associates with JUN/AP-1 to activate transcription (PubMed:22083952). Also able to bind to a minimal DNA heteroduplex containing a G/T-mismatch with 5'-TRT[G/T]NB-3' sequence (PubMed:20097901). Binds to NFAT-like motifs (purine-rich) in the IL2 promoter (PubMed:1339390). Positively regulates WNT/beta-catenin signaling by translocating DVL proteins into the nucleus (PubMed:25805136). Also binds to HIV-1 long terminal repeat. May be involved in both positive and negative regulation of important viral and cellular promoter elements (PubMed:1909027). Accessory component of the polycomb repressive deubiquitinase (PR-DUB) complex; recruits the PR-DUB complex to specific FOXK2-bound genes (PubMed:24634419, PubMed:30664650)

Protein Sequence

10 MAAAAAALSG 20 AGTPPAGGGA 30 GGGGAGGGGS 40 PPGGWAVARL 50 EGREFEYLMK 60 KRSVTIGRNS 70 SQGSVDVSMG 80 HSSFISRRHL 90 EIFTPPGGGG 100 HGGAAPELPP 110 AQPRPDAGGD 120 FYLRCLGKNG 130 VFVDGVFQRR 140 GAPPLQLPRV 150 CTFRFPSTNI 160 KITFTALSSE 170 KREKQEASES 180 PVKAVQPHIS 190 PLTINIPDTM 200 AHLISPLPSP 210 TGTISAANSC 220 PSSPRGAGSS 230 GYKVGRVMPS 240 DLNLMADNSQ 250 PENEKEASGG 260 DSPKDDSKPP 270 YSYAQLIVQA 280 ITMAPDKQLT 290 LNGIYTHITK 300 NYPYYRTADK 310 GWQNSIRHNL 320 SLNRYFIKVP 330 RSQEEPGKGS 340 FWRIDPASES 350 KLIEQAFRKR 360 RPRGVPCFRT 370 PLGPLSSRSA 380 PASPNHAGVL 390 SAHSSGAQTP 400 ESLSREGSPA 410 PLEPEPGAAQ 420 PKLAVIQEAR 430 FAQSAPGSPL 440 SSQPVLITVQ 450 RQLPQAIKPV 460 TYTVATPVTT 470 STSQPPVVQT 480 VHVVHQIPAV 490 SVTSVAGLAP 500 ANTYTVSGQA 510 VVTPAAVLAP 520 PKAEAQENGD 530 HREVKVKVEP 540 IPAIGHATLG 550 TASRIIQTAQ 560 TTPVQTVTIV 570 QQAPLGQHQL 580 PIKTVTQNGT 590 HVASVPTAVH 600 GQVNNAAASP 610 LHMLATHASA 620 SASLPTKRHN 630 GDQPEQPELK 640 RIKTEDGEGI 650 VIALSVDTPP 660 AAVREKGVQN

Gene Ontology

Classification GO ID Description
Cellular Component GO:0000785 chromatin
Cellular Component GO:0005737 cytoplasm
Cellular Component GO:0005654 nucleoplasm
Cellular Component GO:0005634 nucleus
Molecular Function GO:0001228 DNA-binding transcription activator activity, RNA polymerase II-specific
Molecular Function GO:0003700 DNA-binding transcription factor activity
Molecular Function GO:0000981 DNA-binding transcription factor activity, RNA polymerase II-specific
Molecular Function GO:0001227 DNA-binding transcription repressor activity, RNA polymerase II-specific
Molecular Function GO:0000287 magnesium ion binding
Molecular Function GO:0000978 RNA polymerase II cis-regulatory region sequence-specific DNA binding
Molecular Function GO:0043565 sequence-specific DNA binding
Molecular Function GO:0000976 transcription cis-regulatory region binding
Biological Process GO:0061621 canonical glycolysis
Biological Process GO:0006351 DNA-templated transcription
Biological Process GO:0001678 intracellular glucose homeostasis
Biological Process GO:0010507 negative regulation of autophagy
Biological Process GO:0045892 negative regulation of DNA-templated transcription
Biological Process GO:0045893 positive regulation of DNA-templated transcription
Biological Process GO:0045944 positive regulation of transcription by RNA polymerase II
Biological Process GO:0006355 regulation of DNA-templated transcription
Biological Process GO:0010906 regulation of glucose metabolic process
Biological Process GO:0006357 regulation of transcription by RNA polymerase II
Biological Process GO:0042594 response to starvation

Reference

[1] Yang D, Yin J, Shan L, Yi X, Zhang W et al.. Identification of lysine-lactylated substrates in gastric cancer cells.. iScience 25(7):104630. 2022 Jul 15. PMID: 35800753.

[2] Cheng Z, Huang H, Li M, Chen Y. Proteomic analysis identifies PFKP lactylation in SW480 colon cancer cells.. iScience 27(1):108645. 2024 Jan 19. PMID: 38155775.

[3] He C, Zhang J, Bai X, Lu C, Zhang K. Lysine lactylation-based insight to understanding the characterization of cervical cancer.. Biochim Biophys Acta Mol Basis Dis 1870(7):167356. 2024 Oct. PMID: 39025375.

[4] He J, Lai T, Zhou Z, Yang H, Lei Z et al.. Multiomics profiling reveals the involvement of protein lactylation in nonhomologous end joining pathway conferring radioresistance in lung adenocarcinoma cell.. Sci Rep 15(1):24651. 2025 Jul 9. PMID: 40634431.

[5] Wu Q, Li Z, Gong T, Zheng X, Zhou X et al.. Porphyromonas gingivalis infection induces lysine lactylation reprogramming in human umbilical vein endothelial cells.. Front Cell Infect Microbiol 16:1706727. 2026. PMID: 41696360.