FOXK1

Protein-coding gene in the species Homo sapiens

FOXK1
Available structures
PDBOrtholog search: PDBe RCSB
List of PDB id codes

2A3S, 2D2W

Identifiers
AliasesFOXK1, FOXK1L, forkhead box K1
External IDsOMIM: 616302; MGI: 1347488; HomoloGene: 82414; GeneCards: FOXK1; OMA:FOXK1 - orthologs
Gene location (Human)
Chromosome 7 (human)
Chr.Chromosome 7 (human)[1]
Chromosome 7 (human)
Genomic location for FOXK1
Genomic location for FOXK1
Band7p22.1Start4,682,295 bp[1]
End4,771,442 bp[1]
Gene location (Mouse)
Chromosome 5 (mouse)
Chr.Chromosome 5 (mouse)[2]
Chromosome 5 (mouse)
Genomic location for FOXK1
Genomic location for FOXK1
Band5 G2|5 81.53 cMStart142,387,252 bp[2]
End142,447,766 bp[2]
RNA expression pattern
Bgee
HumanMouse (ortholog)
Top expressed in
  • skin of arm

  • tendon of biceps brachii

  • cerebellar vermis

  • cardiac muscle tissue of right atrium

  • internal globus pallidus

  • pons

  • myocardium of left ventricle

  • middle temporal gyrus

  • superior vestibular nucleus

  • thalamus
Top expressed in
  • ascending aorta

  • aortic valve

  • Paneth cell

  • ciliary body

  • cumulus cell

  • gastrula

  • retinal pigment epithelium

  • supraoptic nucleus

  • secondary oocyte

  • primitive streak
More reference expression data
BioGPS


More reference expression data
Gene ontology
Molecular function
  • DNA-binding transcription factor activity
  • DNA binding
  • sequence-specific DNA binding
  • RNA polymerase II transcription regulatory region sequence-specific DNA binding
  • protein binding
  • DNA-binding transcription factor activity, RNA polymerase II-specific
  • transcription cis-regulatory region binding
  • DNA-binding transcription activator activity, RNA polymerase II-specific
  • DNA-binding transcription repressor activity, RNA polymerase II-specific
Cellular component
  • nucleus
  • nucleoplasm
  • cytoplasm
Biological process
  • regulation of transcription by RNA polymerase II
  • 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 by RNA polymerase II
  • positive regulation of transcription by RNA polymerase II
Sources:Amigo / QuickGO
Orthologs
SpeciesHumanMouse
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 MbChr 5: 142.39 – 142.45 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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

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. ^ a b c GRCh38: Ensembl release 89: ENSG00000164916 – Ensembl, May 2017
  2. ^ a b c 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 (July 2004). "Identification and characterization of human FOXK1 gene in silico". International Journal of Molecular Medicine. 14 (1): 127–132. doi:10.3892/ijmm.14.1.127. PMID 15202027.
  6. ^ "Entrez Gene: FOXK1 forkhead box K1".
  7. ^ a b Sukonina V, Ma H, Zhang W, Bartesaghi S, Subhash S, Heglind M, et al. (February 2019). "FOXK1 and FOXK2 regulate aerobic glycolysis". Nature. 566 (7743): 279–283. Bibcode:2019Natur.566..279S. doi:10.1038/s41586-019-0900-5. PMID 30700909. S2CID 59524697.

Further reading

  • Ewing RM, Chu P, Elisma F, Li H, Taylor P, Climie S, et al. (2007). "Large-scale mapping of human protein-protein interactions by mass spectrometry". Molecular Systems Biology. 3 (1): 89. doi:10.1038/msb4100134. PMC 1847948. PMID 17353931.
  • Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, et al. (November 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–648. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.
  • Tsai KL, Huang CY, Chang CH, Sun YJ, Chuang WJ, Hsiao CD (June 2006). "Crystal structure of the human FOXK1a-DNA complex and its implications on the diverse binding specificity of winged helix/forkhead proteins". The Journal of Biological Chemistry. 281 (25): 17400–17409. doi:10.1074/jbc.M600478200. PMID 16624804.
  • Huang JT, Lee V (September 2004). "Identification and characterization of a novel human FOXK1 gene in silico". International Journal of Oncology. 25 (3): 751–757. doi:10.3892/ijo.25.3.751. PMID 15289879.
  • v
  • t
  • e
  • 2a3s: Solution structure and Dynamics of DNA-Binding Domain of Myocyte Nuclear Factor
    2a3s: Solution structure and Dynamics of DNA-Binding Domain of Myocyte Nuclear Factor
  • 2d2w: Solution structure and Dynamics of the DNA-Binding Domain of Myocyte Nuclear Factor
    2d2w: Solution structure and Dynamics of the DNA-Binding Domain of Myocyte Nuclear Factor
  • v
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  • e
(1) Basic domains
(1.1) Basic leucine zipper (bZIP)
(1.2) Basic helix-loop-helix (bHLH)
Group A
Group B
Group C
bHLH-PAS
Group D
Group E
Group F
bHLH-COE
(1.3) bHLH-ZIP
(1.4) NF-1
(1.5) RF-X
(1.6) Basic helix-span-helix (bHSH)
(2) Zinc finger DNA-binding domains
(2.1) Nuclear receptor (Cys4)
subfamily 1
subfamily 2
subfamily 3
subfamily 4
subfamily 5
subfamily 6
subfamily 0
(2.2) Other Cys4
(2.3) Cys2His2
(2.4) Cys6
(2.5) Alternating composition
(2.6) WRKY
(3) Helix-turn-helix domains
(3.1) Homeodomain
Antennapedia
ANTP class
protoHOX
Hox-like
metaHOX
NK-like
other
(3.2) Paired box
(3.3) Fork head / winged helix
(3.4) Heat shock factors
(3.5) Tryptophan clusters
(3.6) TEA domain
  • transcriptional enhancer factor
(4) β-Scaffold factors with minor groove contacts
(4.1) Rel homology region
(4.2) STAT
(4.3) p53-like
(4.4) MADS box
(4.6) TATA-binding proteins
(4.7) High-mobility group
(4.9) Grainyhead
(4.10) Cold-shock domain
(4.11) Runt
(0) Other transcription factors
(0.2) HMGI(Y)
(0.3) Pocket domain
(0.5) AP-2/EREBP-related factors
(0.6) Miscellaneous
see also transcription factor/coregulator deficiencies
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