FOXK1 - Wikipedia

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Appearance move to sidebar hide From Wikipedia, the free encyclopedia Protein-coding gene in the species Homo sapiens

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; OMA:FOXK1 - orthologs
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 142,387,252 bp[2] End 142,447,766 bp[2]
RNA expression pattern Bgee Human Mouse (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 Species Human Mouse Entrez 221937 17425 Ensembl ENSG00000164916 ENSMUSG00000056493 UniProt P85037 P42128 RefSeq (mRNA) NM_001037165 NM_010812NM_199068 RefSeq (protein) NP_001032242 NP_951031 Location (UCSC) Chr 7: 4.68 – 4.77 Mb Chr 5: 142.39 – 142.45 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/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

[edit]

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

[edit]

• 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 PDB gallery
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

v t e Transcription factors and intracellular receptors
(1) Basic domains (1.1) Basic leucine zipper (bZIP) Activating transcription factor AATF 1 2 3 4 5 6 7 AP-1 c-Fos FOSB FOSL1 FOSL2 JDP2 c-Jun JUNB JunD BACH 1 2 BATF BLZF1 C/EBP α β γ δ ε ζ CREB 1 3 L1 CREM DBP DDIT3 GABPA GCN4 HLF MAF B sMaf F G K NFE 2 L1 L2 L3 NFIL3 NRL NRF 1 2 3 XBP1 (1.2) Basic helix-loop-helix (bHLH) Group A AS-C ASCL1 ASCL2 ATOH1 HAND 1 2 MESP2 Myogenic regulatory factors MyoD Myogenin MYF5 MYF6 NeuroD 1 2 Neurogenins 1 2 3 OLIG 1 2 Paraxis TCF15 Scleraxis SLC LYL1 TAL 1 2 Twist Group B FIGLA Myc c-Myc l-Myc n-Myc MXD4 TCF4 Group CbHLH-PAS AhR AHRR ARNT ARNTL ARNTL2 CLOCK HIF 1A EPAS1 3A NPAS 1 2 3 PER 1 2 3 Period SIM 1 2 Group D DEC 1 2 BHLHA9 Pho4 ID 1 2 3 4 Group E HES 1 2 3 4 5 6 7 HEY 1 2 L Group FbHLH-COE EBF1 (1.3) bHLH-ZIP AP-4 MAX MXD1 MXD3 MITF MNT MLX MLXIPL MXI1 Myc SREBP 1 2 USF1 (1.4) NF-1 NFI A B C X SMAD R-SMAD 1 2 3 5 9 I-SMAD 6 7 4) (1.5) RF-X RFX 1 2 3 4 5 6 ANK (1.6) Basic helix-span-helix (bHSH) AP-2 α β γ δ ε
(2) Zinc finger DNA-binding domains (2.1) Nuclear receptor (Cys4) subfamily 1 Thyroid hormone α β CAR FXR LXR α β PPAR α β/δ γ PXR RAR α β γ ROR α β γ Rev-ErbA α β VDR subfamily 2 COUP-TF (I II Ear-2 HNF4 α γ PNR RXR α β γ Testicular receptor 2 4 TLX subfamily 3 Steroid hormone Androgen Estrogen α β Glucocorticoid Mineralocorticoid Progesterone Estrogen related α β γ subfamily 4 NUR NGFIB NOR1 NURR1 subfamily 5 LRH-1 SF1 subfamily 6 GCNF subfamily 0 DAX1 SHP (2.2) Other Cys4 GATA 1 2 3 4 5 6 MTA 1 2 3 TRPS1 (2.3) Cys2His2 General transcription factors TFIIA TFIIB TFIID TFIIE 1 2 TFIIF 1 2 TFIIH 1 2 4 2I 3A 3C1 3C2 ATBF1 BCL 6 11A 11B CTCF E4F1 EGR 1 2 3 4 ERV3 GFI1 GLI family 1 2 3 REST S1 S2 YY1 HIC 1 2 HIVEP 1 2 3 IKZF 1 2 3 ILF 2 3 Sp/KLF family KLF 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 17 SP 1 2 4 7 8 MTF1 MYT1 OSR1 PRDM9 SALL 1 2 3 4 TSHZ3 WT1 Zbtb7 7A 7B ZBTB 11 16 17 20 21 32 33 40 zinc finger 3 7 9 10 19 22 24 33B 34 35 41 43 44 51 74 143 146 148 165 202 217 219 238 239 259 267 268 281 300 318 330 346 350 365 366 384 423 451 452 471 593 638 644 649 655 804A (2.4) Cys6 HIVEP1 (2.5) Alternating composition AIRE DIDO1 GRLF1 ING 1 2 4 JARID 1A 1B 1C 1D 2 JMJD1B (2.6) WRKY WRKY
(3) Helix-turn-helix domains (3.1) Homeodomain AntennapediaANTP class protoHOXHox-like ParaHox Gsx 1 2 Xlox PDX1 Cdx 1 2 4 extended Hox: Evx1 Evx2 MEOX1 MEOX2 Homeobox A1 A2 A3 A4 A5 A7 A9 A10 A11 A13 B1 B2 B3 B4 B5 B6 B7 B8 B9 B13 C4 C5 C6 C8 C9 C10 C11 C12 C13 D1 D3 D4 D8 D9 D10 D11 D12 D13 GBX1 GBX2 MNX1 metaHOXNK-like BARHL1 BARHL2 BARX1 BARX2 BSX DBX 1 2 DLX 1 2 3 4 5 6 EMX 1 2 EN 1 2 HHEX HLX LBX1 LBX2 MSX 1 2 NANOG NKX 2-1 2-2 2-3 2-5 3-1 3-2 HMX1 HMX2 HMX3 6-1 6-2 NOTO TLX1 TLX2 TLX3 VAX1 VAX2 other ARX CRX CUTL1 FHL 1 2 3 HESX1 HOPX LMX 1A 1B NOBOX TALE IRX 1 2 3 4 5 6 MKX MEIS 1 2 PBX 1 2 3 PKNOX 1 2 SIX 1 2 3 4 5 PHF 1 3 6 8 10 16 17 20 21A POU domain PIT-1 BRN-3: A B C Octamer transcription factor: 1 2 3/4 6 7 11 SATB2 ZEB 1 2 (3.2) Paired box PAX 1 2 3 4 5 6 7 8 9 PRRX 1 2 PROP1 PHOX 2A 2B RAX SHOX SHOX2 VSX1 VSX2 Bicoid GSC BICD2 OTX 1 2 PITX 1 2 3 (3.3) Fork head / winged helix E2F 1 2 3 4 5 FOX proteins A1 A2 A3 B1 B2 C1 C2 D1 D2 D3 D4 D4L1 D4L3 D4L4 D4L5 D4L6 E1 E3 F1 F2 G1 H1 I1 I2 I3 J1 J2 J3 K1 K2 L1 L2 M1 N1 N2 N3 N4 O1 O3 O4 O6 P1 P2 P3 P4 Q1 R1 R2 S1 (3.4) Heat shock factors HSF 1 2 4 (3.5) Tryptophan clusters ELF 2 4 5 EHF ELK 1 3 4 ERF ETS 1 2 ERG SPIB ETV 1 4 5 6 FLI1 Interferon regulatory factors 1 2 3 4 5 6 7 8 MYB MYBL2 (3.6) TEA domain transcriptional enhancer factor 1 2 3 4
(4) β-Scaffold factors with minor groove contacts (4.1) Rel homology region NF-κB NFKB1 NFKB2 REL RELA RELB NFAT C1 C2 C3 C4 5 (4.2) STAT STAT 1 2 3 4 5 6 (4.3) p53-like p53 p63 p73 family p53 TP63 p73 TBX 1 2 3 5 19 21 22 TBR1 TBR2 TFT MYRF (4.4) MADS box Mef2 A B C D SRF (4.6) TATA-binding proteins TBP TBPL1 (4.7) High-mobility group BBX HMGB 1 2 3 4 HMGN 1 2 3 4 HNF 1A 1B SOX 1 2 3 4 5 6 8 9 10 11 12 13 14 15 17 18 21 SRY SSRP1 TCF/LEF TCF 1 3 4 LEF1 TOX 1 2 3 4 (4.9) Grainyhead TFCP2 (4.10) Cold-shock domain CSDA YBX1 (4.11) Runt CBF CBFA2T2 CBFA2T3 RUNX1 RUNX2 RUNX3 RUNX1T1
(0) Other transcription factors (0.2) HMGI(Y) HMGA 1 2 HBP1 (0.3) Pocket domain Rb RBL1 RBL2 (0.5) AP-2/EREBP-related factors Apetala 2 EREBP B3 (0.6) Miscellaneous ARID 1A 1B 2 3A 3B 4A CAP IFI 16 35 MLL 2 3 T1 MNDA NFY A B C Rho/Sigma
see also transcription factor/coregulator deficiencies

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