FOXK1
entrez
221937
canonical
uniprot
P85037
canonical
ensembl
ENSG00000164916
resolver
ensp
ENSP00000328720
resolver
genesymbol
FOXK1
resolver
genesymbol_syn
MNF
resolver
hgnc
HGNC:23480
resolver
uniprot_entry
FOXK1_HUMAN
resolver
amino_acid_sequence
MAEVGEDSGARALLALRSAPCSPVLCAAAAAAAFPAAAPPPAPAQPQPPPGPPPPPPPPLPPGAIAGAGSSGGSSGVSGDSAVAGAAPALVAAAAASVRQSPGPALARLEGREFEFLMRQPSVTIGRNSSQGSVDLSMGLSSFISRRHLQLSFQEPHFYLRCLGKNGVFVDGAFQRRGAPALQLPKQCTFRFPSTAIKIQFTSLYHKEEAPASPLRPLYPQISPLKIHIPEPDLRSMVSPVPSPTGTISVPNSCPASPRGAGSSSYRFVQNVTSDLQLAAEFAAKAASEQQADTSGGDSPKDESKPPFSYAQLIVQAISSAQDRQLTLSGIYAHITKHYPYYRTADKGWQNSIRHNLSLNRYFIKVPRSQEEPGKGSFWRIDPASEAKLVEQAFRKRRQRGVSCFRTPFGPLSSRSAPASPTHPGLMSPRSGGLQTPECLSREGSPIPHDPEFGSKLASVPEYRYSQSAPGSPVSAQPVIMAVPPRPSSLVAKPVAYMPASIVTSQQPAGHAIHVVQQAPTVTMVRVVTTSANSANGYILTSQGAAGGSHDAAGAAVLDLGSEARGLEEKPTIAFATIPAAGGVIQTVASQMAPGVPGHTVTILQPATPVTLGQHHLPVRAVTQNGKHAVPTNSLAGNAYALTSPLQLLATQASSSAPVVVTRVCEVGPKEPAAAVAATATTTPATATTASASASSTGEPEVKRSRVEEPSGAVTTPAGVIAAAGPQGPGTGE
uniprot
proteins
function
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). {ECO:0000250|UniProtKB:P42128, ECO:0000269|PubMed:17670796, ECO:0000269|PubMed:24634419, ECO:0000269|PubMed:25805136, ECO:0000269|PubMed:25852164, ECO:0000269|PubMed:30664650, ECO:0000269|PubMed:40246981}.
uniprot
proteins
mass_dalton
75457
uniprot
proteins
mutagenesis
MUTAGEN 127; /note="R->A: Reduced interaction with BAP1."; /evidence="ECO:0000269|PubMed:25451922"; MUTAGEN 355; /note="H->A: Reduced DNA-binding and ability to repress transcription without affecting interaction with SRF. No effect on interaction with DVL2."; /evidence="ECO:0000269|PubMed:17670796, ECO:0000269|PubMed:25805136"; MUTAGEN 441; /note="S->A: Abolished phosphorylation by isoform Beta-II of PRKCB."; /evidence="ECO:0000269|PubMed:40246981
uniprot
proteins
post_translational_modification
PTM: Phosphorylation by GSK3 (GSK3A or GSK3B) promotes interaction with YWHAE/14-3-3-epsilon and retention in the cytoplasm (By similarity). In response to mTORC1 signaling, phosphorylation by GSK3 is prevented, leading to translocation to the nucleus (By similarity). Phosphorylation at Ser-441 by isoform Beta-II of PRKCB promotes expression and secretion of LGALS13 (PubMed:40246981). {ECO:0000250|UniProtKB:P42128, ECO:0000269|PubMed:40246981}.
uniprot
proteins
pubmed
12853948
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15202027
uniprot
proteins
pubmed
15289879
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
17081983
uniprot
proteins
pubmed
17670796
uniprot
proteins
pubmed
18220336
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
24634419
uniprot
proteins
pubmed
25451922
uniprot
proteins
pubmed
25805136
uniprot
proteins
pubmed
25852164
uniprot
proteins
pubmed
30664650
uniprot
proteins
pubmed
40246981
uniprot
proteins
sequence_length
733
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:25805136, ECO:0000269|PubMed:25852164}. Cytoplasm {ECO:0000269|PubMed:25805136, ECO:0000269|PubMed:25852164}. Note=Translocation to the nucleus is regulated by phosphorylation: phosphorylation by GSK3 (GSK3A or GSK3B) promotes interaction with 14-3-3 proteins and sequestration in the cytoplasm. Dephosphorylation promotes translocation to the nucleus (By similarity). Accumulates in the nucleus upon viral infection (PubMed:25852164). {ECO:0000250|UniProtKB:P42128, ECO:0000269|PubMed:25852164}.
uniprot
proteins