Search Results

Overview

Uniprot ID	P85037
Protein Name	Forkhead box protein K1
Gene Name	FOXK1
Organism	Homo sapiens

Kla Sites from experimental identification

Position	Flanking peptide
347	PYYRTADKGWQNSIR
375	RSQEEPGKGSFWRID
456	HDPEFGSKLASVPEY

Function

Transcriptional regulator involved in different processes such as glucose metabolism, aerobic glycolysis, muscle cell differentiation and autophagy (By similarity). 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:17670796). Together with FOXK2, 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). Involved in mTORC1-mediated metabolic reprogramming: in response to mTORC1 signaling, translocates into the nucleus and regulates the expression of genes associated with glycolysis and downstream anabolic pathways, such as HIF1A, thereby regulating glucose metabolism (By similarity). Together with FOXK2, 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). Acts as a transcriptional regulator of the myogenic progenitor cell population in skeletal muscle (By similarity). Binds to the upstream enhancer region (CCAC box) of myoglobin (MB) gene, regulating the myogenic progenitor cell population (By similarity). Promotes muscle progenitor cell proliferation by repressing the transcriptional activity of FOXO4, thereby inhibiting myogenic differentiation (By similarity). Involved in remodeling processes of adult muscles that occur in response to physiological stimuli (By similarity). Required to correct temporal orchestration of molecular and cellular events necessary for muscle repair (By similarity). Represses myogenic differentiation by inhibiting MEFC activity (By similarity). Positively regulates Wnt/beta-catenin signaling by translocating DVL into the nucleus (PubMed:25805136). Reduces virus replication, probably by binding the interferon stimulated response element (ISRE) to promote antiviral gene expression (PubMed:25852164). Accessory component of the polycomb repressive deubiquitinase (PR-DUB) complex; recruits the PR-DUB complex to specific FOXK1-bound genes (PubMed:24634419, PubMed:30664650). Acts as an indirect positive regulator of ferroptosis following phosphorylation by isoform Beta-II of PRKCB by promoting expression and subsequent secretion of LGALS13 (PubMed:40246981)

Protein Sequence

10 MAEVGEDSGA 20 RALLALRSAP 30 CSPVLCAAAA 40 AAAFPAAAPP 50 PAPAQPQPPP 60 GPPPPPPPPL 70 PPGAIAGAGS 80 SGGSSGVSGD 90 SAVAGAAPAL 100 VAAAAASVRQ 110 SPGPALARLE 120 GREFEFLMRQ 130 PSVTIGRNSS 140 QGSVDLSMGL 150 SSFISRRHLQ 160 LSFQEPHFYL 170 RCLGKNGVFV 180 DGAFQRRGAP 190 ALQLPKQCTF 200 RFPSTAIKIQ 210 FTSLYHKEEA 220 PASPLRPLYP 230 QISPLKIHIP 240 EPDLRSMVSP 250 VPSPTGTISV 260 PNSCPASPRG 270 AGSSSYRFVQ 280 NVTSDLQLAA 290 EFAAKAASEQ 300 QADTSGGDSP 310 KDESKPPFSY 320 AQLIVQAISS 330 AQDRQLTLSG 340 IYAHITKHYP 350 YYRTADKGWQ 360 NSIRHNLSLN 370 RYFIKVPRSQ 380 EEPGKGSFWR 390 IDPASEAKLV 400 EQAFRKRRQR 410 GVSCFRTPFG 420 PLSSRSAPAS 430 PTHPGLMSPR 440 SGGLQTPECL 450 SREGSPIPHD 460 PEFGSKLASV 470 PEYRYSQSAP 480 GSPVSAQPVI 490 MAVPPRPSSL 500 VAKPVAYMPA 510 SIVTSQQPAG 520 HAIHVVQQAP 530 TVTMVRVVTT 540 SANSANGYIL 550 TSQGAAGGSH 560 DAAGAAVLDL 570 GSEARGLEEK 580 PTIAFATIPA 590 AGGVIQTVAS 600 QMAPGVPGHT 610 VTILQPATPV 620 TLGQHHLPVR 630 AVTQNGKHAV 640 PTNSLAGNAY 650 ALTSPLQLLA 660 TQASSSAPVV 670 VTRVCEVGPK 680 EPAAAVAATA 690 TTTPATATTA 700 SASASSTGEP 710 EVKRSRVEEP 720 SGAVTTPAGV 730 IAAAGPQGPG TGE

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:0071889	14-3-3 protein binding
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:0000978	RNA polymerase II cis-regulatory region sequence-specific DNA binding
Molecular Function	GO:1990837	sequence-specific double-stranded DNA binding
Molecular Function	GO:0000976	transcription cis-regulatory region binding
Biological Process	GO:0061621	canonical glycolysis
Biological Process	GO:0030154	cell differentiation
Biological Process	GO:0006351	DNA-templated transcription
Biological Process	GO:0001678	intracellular glucose homeostasis
Biological Process	GO:0007517	muscle organ development
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: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] 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.

[2] 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.