{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"Q01167","secondaryAccessions":["A6NEP5","Q13622","Q13623","Q13624"],"uniProtkbId":"FOXK2_HUMAN","entryAudit":{"firstPublicDate":"1993-04-01","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2006-11-28","entryVersion":241,"sequenceVersion":3},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"evidences":[{"evidenceCode":"ECO:0000305"}],"value":"Forkhead box protein K2"}},"alternativeNames":[{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"20097901"}],"value":"G/T-mismatch specific binding protein"},"shortNames":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"20097901"}],"value":"nGTBP"}]},{"fullName":{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"12402362"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"1909027"}],"value":"Interleukin enhancer-binding factor 1"}}]},"genes":[{"geneName":{"value":"FOXK2"},"synonyms":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"1339390"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"1909027"}],"value":"ILF"},{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"12402362"}],"value":"ILF1"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q3UCQ1"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1339390"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1909027"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20097901"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22083952"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24634419"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25451922"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25805136"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30664650"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38735474"}],"value":"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)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q3UCQ1"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24634419"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24748658"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25451922"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25805136"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30664650"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38735474"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"24634419"}],"value":"Component of SIN3A-, but not SIN3B-, containing multiprotein complexes (By similarity). Interacts with DVL1, DVL2 (when phosphorylated) and DVL3; the interaction induces DVL2 nuclear translocation (PubMed:25805136). Interacts with SUDS3 (PubMed:25805136). Interacts with BAP1 (when phosphorylated); leading to recruit the PR-DUB complex and repress FOXK2 target genes (PubMed:24748658, PubMed:25451922). Accessory component of the polycomb repressive deubiquitinase (PR-DUB) complex, at least composed of BAP1, one of ASXL1, ASXL2 or (probably) ASXL3 and one of MBD5 or MBD6 (PubMed:24634419, PubMed:30664650). The PR-DUB core associates with a number of accessory proteins, including FOXK1, FOXK2, KDM1B, HCFC1 and OGT (Probable) (PubMed:30664650). Interacts with FBXO24 (PubMed:38735474)"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"Q01167","intActId":"EBI-2509991"},"interactantTwo":{"uniProtKBAccession":"P14316","geneName":"IRF2","intActId":"EBI-2866589"},"numberOfExperiments":5,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"Q01167","intActId":"EBI-2509991"},"interactantTwo":{"uniProtKBAccession":"P61244","geneName":"MAX","intActId":"EBI-751711"},"numberOfExperiments":4,"organismDiffer":false}]},{"commentType":"SUBCELLULAR LOCATION","subcellularLocations":[{"location":{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20810654"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"24748658"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25805136"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38735474"}],"value":"Nucleus","id":"SL-0191"}},{"location":{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"Q3UCQ1"}],"value":"Cytoplasm","id":"SL-0086"}}]},{"commentType":"ALTERNATIVE PRODUCTS","events":["Alternative splicing"],"isoforms":[{"name":{"value":"1"},"isoformIds":["Q01167-1"],"isoformSequenceStatus":"Displayed"},{"name":{"value":"2"},"isoformIds":["Q01167-2"],"sequenceIds":["VSP_001559"],"isoformSequenceStatus":"Described"},{"name":{"value":"3"},"isoformIds":["Q01167-3"],"sequenceIds":["VSP_001560","VSP_001561"],"isoformSequenceStatus":"Described"}]},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"1339390"}],"value":"Expressed in both lymphoid and non-lymphoid cells"}],"commentType":"TISSUE SPECIFICITY"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"16624804"}],"value":"The C-terminal part of the DNA-binding domain may contribute to DNA recognition specificity"}],"commentType":"DOMAIN"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20810654"}],"value":"Hyperphosphorylated during mitosis by CDK1 and, to a lower extent, CDK2 (PubMed:20810654). Phosphorylation at Ser-373 and Ser-428 affects stability by promoting degradation (PubMed:20810654)"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"38735474"}],"value":"Ubiquitinated by the SCF-FBXO24 E3 ubiquitin ligase, leading to proteasomal degradation"}],"commentType":"PTM"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000303","source":"PubMed","id":"12402362"},{"evidenceCode":"ECO:0000303","source":"PubMed","id":"16624804"},{"evidenceCode":"ECO:0000305"}],"value":"Was initially named FOXK1a by some reports (PubMed:12402362, PubMed:16624804). 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