Foxk1
entrez
17425
canonical
uniprot
P42128
canonical
ensembl
ENSMUSG00000056493
resolver
ensp
ENSMUSP00000072616
resolver
enst
ENSMUST00000072837
resolver
genesymbol
Foxk1
resolver
genesymbol_syn
Mnf
resolver
uniprot
O35939
resolver
uniprot
Q3UHI6
resolver
uniprot
Q3UN67
resolver
uniprot_entry
FOXK1_MOUSE
resolver
uniprot_sec
O35939
resolver
uniprot_sec
Q3UHI6
resolver
uniprot_sec
Q3UN67
resolver
amino_acid_sequence
MAEVGEDSGARALLALRSAPCSPVLCAAAAAAAFPATTSPPPPAQPPPGPPALPAEPGPGPVPSTVATATTTAPALVAAAAASVRQSPGPALARLEGREFEFLMRQPSVTIGRNSSQGSVDLSMGLSSFISRRHLQLSFQEPHFYLRCLGKNGVFVDGAFQRRGAPALQLPQQCTFRFPSTAIKIQFTSLYHKEEAPASPLRPLYPQISPLKIHIPEPDLRSLVSPIPSPTGTISVPNSCPASPRGAGSSSYRFVQNVTSDLQLAAEFAAKAASEQQADASGGDSPKDESKPPYSYAQLIVQAISSAQDRQLTLSGIYAHITKHYPYYRTADKGWQNSIRHNLSLNRYFIKVPRSQEEPGKGSFWRIDPASEAKLVEQAFRKRRQRGVSCFRTPFGPLSSRSAPASPTHPGLMSPRSSGLQTPECLSREGSPIPHDPDLGSKLASVPEYRYSQSAPGSPVSAQPVIMAVPPRPSNLVAKPVAYMPASIVTSQQPSGHAIHVVQQAPTVTMVRVVTTSANSANGYILASQGSTGTSHDTAGTAVLDLGNEARGLEEKPTIAFATIPAASRVIQTVASQMAPGVPGHTVTILQPATPVTIGQHHLPVRAVTQNGKHAVPTNSLTGNAYALSSPLQLLAAQASSSTPVVITRVCEVGPEEPAAAVSVAANAAPTPAASTTTSASSSGEPEVKRSRVEEPGGTATTQPTAMAATGPQGPGTGE
uniprot
proteins
function
FUNCTION: Transcriptional regulator involved in different processes such as glucose metabolism, aerobic glycolysis, muscle cell differentiation and autophagy (PubMed:25402684, PubMed:29861159, PubMed:30700909). 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:25402684, PubMed:29861159, PubMed:30700909). 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 (PubMed:30700909). 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 (PubMed:30700909). Probably plays a role in gluconeogenesis during overnight fasting, when lactate from white adipose tissue and muscle is the main substrate (PubMed:30700909). 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 (PubMed:29861159). 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 (PubMed:25402684). Acts as a transcriptional regulator of the myogenic progenitor cell population in skeletal muscle (PubMed:12446708, PubMed:22956541, PubMed:8007964, PubMed:9271401). Binds to the upstream enhancer region (CCAC box) of myoglobin (MB) gene, regulating the myogenic progenitor cell population (PubMed:8007964, PubMed:9271401). Promotes muscle progenitor cell proliferation by repressing the transcriptional activity of FOXO4, thereby inhibiting myogenic differentiation (PubMed:12446708, PubMed:22956541). Involved in remodeling processes of adult muscles that occur in response to physiological stimuli (PubMed:22956541, PubMed:9271401). Required to correct temporal orchestration of molecular and cellular events necessary for muscle repair (PubMed:10792059). Represses myogenic differentiation by inhibiting MEFC activity (PubMed:22956541). Positively regulates Wnt/beta-catenin signaling by translocating DVL into the nucleus (By similarity). Reduces virus replication, probably by binding the interferon stimulated response element (ISRE) to promote antiviral gene expression (By similarity). Accessory component of the polycomb repressive deubiquitinase (PR-DUB) complex; recruits the PR-DUB complex to specific FOXK1-bound genes (PubMed:32747411). {ECO:0000250|UniProtKB:P85037, ECO:0000269|PubMed:10792059, ECO:0000269|PubMed:12446708, ECO:0000269|PubMed:22956541, ECO:0000269|PubMed:25402684, ECO:0000269|PubMed:29861159, ECO:0000269|PubMed:30700909, ECO:0000269|PubMed:32747411, ECO:0000269|PubMed:8007964, ECO:0000269|PubMed:9271401}.
uniprot
proteins
mass_dalton
74920
uniprot
proteins
mutagenesis
MUTAGEN 333; /note="K->A: Decreases DNA-binding. No effect on transcriptional repression."; /evidence="ECO:0000269|PubMed:22956541"; MUTAGEN 340; /note="R->A: Abolishes DNA-binding. No effect on transcriptional repression."; /evidence="ECO:0000269|PubMed:22956541"; MUTAGEN 402..406; /note="SAPAS->AAPAA: Decreased phosphorylation by GSK3A and interaction with 14-3-3 proteins."; /evidence="ECO:0000269|PubMed:29861159"; MUTAGEN 427..431; /note="SREGS->AREGA: Decreased phosphorylation by GSK3A and interaction with 14-3-3 proteins."; /evidence="ECO:0000269|PubMed:29861159
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 (PubMed:29861159). In response to mTORC1 signaling, phosphorylation by GSK3 is prevented, leading to translocation to the nucleus (PubMed:29861159). {ECO:0000269|PubMed:29861159}.
uniprot
proteins
pubmed
10620510
uniprot
proteins
pubmed
10792059
uniprot
proteins
pubmed
12446708
uniprot
proteins
pubmed
12449423
uniprot
proteins
pubmed
16141072
uniprot
proteins
pubmed
16376864
uniprot
proteins
pubmed
17242355
uniprot
proteins
pubmed
17363903
uniprot
proteins
pubmed
20013826
uniprot
proteins
pubmed
21183079
uniprot
proteins
pubmed
22476904
uniprot
proteins
pubmed
22956541
uniprot
proteins
pubmed
23714736
uniprot
proteins
pubmed
24129315
uniprot
proteins
pubmed
25402684
uniprot
proteins
pubmed
29861159
uniprot
proteins
pubmed
30700909
uniprot
proteins
pubmed
32747411
uniprot
proteins
pubmed
8007964
uniprot
proteins
pubmed
9271401
uniprot
proteins
sequence_length
719
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20013826, ECO:0000269|PubMed:25402684, ECO:0000269|PubMed:29861159}. Cytoplasm {ECO:0000269|PubMed:25402684, ECO:0000269|PubMed:29861159}. 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 (PubMed:29861159). Dephosphorylation promotes translocation to the nucleus (PubMed:29861159). {ECO:0000269|PubMed:29861159}.
uniprot
proteins