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FOXK1

From Wikipedia, the free encyclopedia
Protein-coding gene in the species Homo sapiens

FOXK1
Available structures
PDBOrtholog search:PDBeRCSB
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
Band7p22.1Start4,682,295bp[1]
End4,771,442bp[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 cMStart142,387,252bp[2]
End142,447,766bp[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
Cellular component
Biological process
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 atranscription factor of theforkhead box family that in humans is encoded by theFOXK1gene.[5][6]

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

FOXK1 and its closely relate siblingFOXK2 induce aerobicglycolysis by upregulating the enzymatic machinery required for this (for example,hexokinase-2,phosphofructokinase,pyruvate kinase, andlactate dehydrogenase), while at the same time suppressing further oxidation of pyruvate in themitochondria by increasing the activity of pyruvate dehydrogenase kinases 1 and 4. Together with suppression of the catalytic subunit ofpyruvate dehydrogenase phosphatase 1 this leads to increasedphosphorylation of the E1α regulatory subunit of thepyruvate dehydrogenase complex, which in turn inhibits further oxidation ofpyruvate in the mitochondria—instead,pyruvate is reduced tolactate. Suppression of FOXK1 and FOXK2 induce the oppositephenotype. Bothin vitro andin 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

[edit]
  1. ^abcGRCh38: Ensembl release 89: ENSG00000164916Ensembl, May 2017
  2. ^abcGRCm38: Ensembl release 89: ENSMUSG00000056493Ensembl, 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. ^abSukonina 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

[edit]
PDB gallery
  • 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
(1) Basic domains
(1.1) Basicleucine 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
(3.1)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
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