FOXK1

Forkhead box protein K1 is a transcription factor of the forkhead box family that in humans is encoded by the FOXK1 gene.[5][6]

FOXK1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2A3S, 2D2W
Identifiers
Aliases	FOXK1, FOXK1L, forkhead box K1
External IDs	OMIM: 616302 MGI: 1347488 HomoloGene: 82414 GeneCards: FOXK1
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7p22.1 Start 4,682,295 bp[1] End 4,771,442 bp[1]
Gene location (Mouse) Chr. Chromosome 5 (mouse)[2] Band 5 G2|5 81.53 cM Start 142,401,497 bp[2] End 142,462,011 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001131, GO:0001151, GO:0001130, GO:0001204 DNA-binding transcription factor activity • DNA binding • sequence-specific DNA binding • RNA polymerase II regulatory region sequence-specific DNA binding • GO:0001948 protein binding • GO:0001200, GO:0001133, GO:0001201 DNA-binding transcription factor activity, RNA polymerase II-specific • transcription regulatory region sequence-specific DNA binding • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific • GO:0001078, GO:0001214, GO:0001206 DNA-binding transcription repressor activity, RNA polymerase II-specific Cellular component • cell nucleus • nucleoplasm • cytoplasm Biological process • regulation of transcription from RNA polymerase II promoter • positive regulation of transcription, DNA-templated • multicellular organism development • muscle organ development • negative regulation of transcription, DNA-templated • regulation of transcription, DNA-templated • transcription, DNA-templated • protein deubiquitination • anatomical structure morphogenesis • cell differentiation • negative regulation of transcription from RNA polymerase II promoter • positive regulation of transcription from RNA polymerase II promoter Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	221937	17425
Ensembl	ENSG00000164916	ENSMUSG00000056493
UniProt	P85037	P42128
RefSeq (mRNA)	NM_001037165	NM_010812 NM_199068
RefSeq (protein)	NP_001032242	NP_951031
Location (UCSC)	Chr 7: 4.68 – 4.77 Mb	Chr 5: 142.4 – 142.46 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

During starvation, in type 2 diabetes, in rapidly dividing cells during embryogenesis, in tumors (Warburg effect) and during T cell proliferation, aerobic glycolysis is induced to produce the building block to sustain growth. FOXK1 is one of the transcription factors managing the passage from the normal cellular respiration (complete glucose oxidation) to generating ATP and intermediaries for many other biochemical pathways.[7]

FOXK1 and its closely relate sibling FOXK2 induce aerobic glycolysis by upregulating the enzymatic machinery required for this (for example, hexokinase-2, phosphofructokinase, pyruvate kinase, and lactate dehydrogenase), while at the same time suppressing further oxidation of pyruvate in the mitochondria by increasing the activity of pyruvate dehydrogenase kinases 1 and 4. Together with suppression of the catalytic subunit of pyruvate dehydrogenase phosphatase 1 this leads to increased phosphorylation of the E1α regulatory subunit of the pyruvate dehydrogenase complex, which in turn inhibits further oxidation of pyruvate in the mitochondria—instead, pyruvate is reduced to lactate. Suppression of FOXK1 and FOXK2 induce the opposite phenotype. Both in vitro and in vivo experiments, including studies of primary human cells, show how FOXK1 and/or FOXK2 are likely to act as important regulators that reprogram cellular metabolism to induce aerobic glycolysis.[7]

References

1. GRCh38: Ensembl release 89: ENSG00000164916 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000056493 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Katoh M, Katoh M (Jun 2004). "Identification and characterization of human FOXK1 gene in silico". Int J Mol Med. 14 (1): 127–32. doi:10.3892/ijmm.14.1.127. PMID 15202027.
6. "Entrez Gene: FOXK1 forkhead box K1".
7. Sukonina, Valentina; Ma, Haixia; Zhang, Wei; Bartesaghi, Stefano; Subhash, Santhilal; Heglind, Mikael; Foyn, Håvard; Betz, Matthias J.; Nilsson, Daniel (Jan 2019). "FOXK1 and FOXK2 regulate aerobic glycolysis". Nature. 566 (7743): 279–283. Bibcode:2019Natur.566..279S. doi:10.1038/s41586-019-0900-5. ISSN 1476-4687. PMID 30700909.

Further reading

• Ewing RM, Chu P, Elisma F, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Mol. Syst. Biol. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
• Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983.
• Tsai KL, Huang CY, Chang CH, et al. (2006). "Crystal structure of the human FOXK1a-DNA complex and its implications on the diverse binding specificity of winged helix/forkhead proteins". J. Biol. Chem. 281 (25): 17400–9. doi:10.1074/jbc.M600478200. PMID 16624804.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Huang JT, Lee V (2005). "Identification and characterization of a novel human FOXK1 gene in silico". Int. J. Oncol. 25 (3): 751–7. doi:10.3892/ijo.25.3.751. PMID 15289879.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Hillier LW, Fulton RS, Fulton LA, et al. (2003). "The DNA sequence of human chromosome 7". Nature. 424 (6945): 157–64. Bibcode:2003Natur.424..157H. doi:10.1038/nature01782. PMID 12853948.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.