UniProtKB - P85037 (FOXK1_HUMAN)
Forkhead box protein K1
FOXK1
Functioni
Transcriptional regulator involved in different processes such as glucose metabolism, aerobic glycolysis, muscle cell differentiation and autophagy (By similarity).
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:17670796).
Together with FOXK2, 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).
Involved in mTORC1-mediated metabolic reprogramming: in response to mTORC1 signaling, translocates into the nucleus and regulates the expression of genes associated with glycolysis and downstream anabolic pathways, such as HIF1A, thereby regulating glucose metabolism (By similarity).
Together with FOXK2, 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).
Acts as a transcriptional regulator of the myogenic progenitor cell population in skeletal muscle (By similarity).
Binds to the upstream enhancer region (CCAC box) of myoglobin (MB) gene, regulating the myogenic progenitor cell population (By similarity).
Promotes muscle progenitor cell proliferation by repressing the transcriptional activity of FOXO4, thereby inhibiting myogenic differentiation (By similarity).
Involved in remodeling processes of adult muscles that occur in response to physiological stimuli (By similarity).
Required to correct temporal orchestration of molecular and cellular events necessary for muscle repair (By similarity).
Represses myogenic differentiation by inhibiting MEFC activity (By similarity).
Positively regulates Wnt/beta-catenin signaling by translocating DVL into the nucleus (PubMed:25805136).
Reduces virus replication, probably by binding the interferon stimulated response element (ISRE) to promote antiviral gene expression (PubMed:25852164).
By similarity3 PublicationsRegions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
DNA bindingi | 305 – 400 | Fork-headPROSITE-ProRule annotationAdd BLAST | 96 |
GO - Molecular functioni
- 14-3-3 protein binding Source: UniProtKB
- DNA-binding transcription factor activity Source: UniProtKB
- DNA-binding transcription factor activity, RNA polymerase II-specific Source: NTNU_SB
- DNA-binding transcription repressor activity, RNA polymerase II-specific Source: UniProtKB
- RNA polymerase II cis-regulatory region sequence-specific DNA binding Source: GO_Central
- sequence-specific double-stranded DNA binding Source: ARUK-UCL
- transcription cis-regulatory region binding Source: UniProtKB
GO - Biological processi
- canonical glycolysis Source: UniProtKB
- cell differentiation Source: UniProtKB-KW
- cellular glucose homeostasis Source: UniProtKB
- muscle organ development Source: UniProtKB-KW
- negative regulation of autophagy Source: UniProtKB
- negative regulation of transcription, DNA-templated Source: UniProtKB
- positive regulation of transcription, DNA-templated Source: UniProtKB
- regulation of glucose metabolic process Source: UniProtKB
- regulation of transcription by RNA polymerase II Source: GO_Central
- response to starvation Source: UniProtKB
Keywordsi
Molecular function | Activator, Developmental protein, DNA-binding, Repressor |
Biological process | Differentiation, Host-virus interaction, Myogenesis, Transcription, Transcription regulation |
Enzyme and pathway databases
PathwayCommonsi | P85037 |
Reactomei | R-HSA-5689603, UCH proteinases |
SignaLinki | P85037 |
Names & Taxonomyi
Protein namesi | Recommended name: Forkhead box protein K12 PublicationsAlternative name(s): Myocyte nuclear factor1 Publication Short name: MNF1 Publication |
Gene namesi | |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:23480, FOXK1 |
MIMi | 616302, gene |
neXtProti | NX_P85037 |
VEuPathDBi | HostDB:ENSG00000164916 |
Subcellular locationi
Nucleus
- Nucleus 2 Publications
Cytoplasm and Cytosol
- Cytoplasm 2 Publications
Note: Translocation to the nucleus is regulated by phosphorylation: phosphorylation by GSK3 (GSK3A or GSK3B) promotes interaction with 14-3-3 proteins and sequestration in the cytoplasm. Dephosphorylation promotes translocation to the nucleus (By similarity). Accumulates in the nucleus upon viral infection (PubMed:25852164).By similarity1 Publication
Nucleus
- nucleoplasm Source: Reactome
- nucleus Source: UniProtKB
Other locations
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 127 | R → A: Reduced interaction with BAP1. 1 Publication | 1 | |
Mutagenesisi | 355 | H → A: Reduced DNA-binding and ability to repress transcription without affecting interaction with SRF. No effect on interaction with DVL2. 2 Publications | 1 |
Organism-specific databases
DisGeNETi | 221937 |
OpenTargetsi | ENSG00000164916 |
PharmGKBi | PA134978307 |
Miscellaneous databases
Pharosi | P85037, Tbio |
Genetic variation databases
BioMutai | FOXK1 |
DMDMi | 118572324 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Initiator methioninei | RemovedCombined sources | |||
ChainiPRO_0000261667 | 2 – 733 | Forkhead box protein K1Add BLAST | 732 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 2 | N-acetylalanineCombined sources | 1 | |
Modified residuei | 101 | PhosphoserineCombined sources | 1 | |
Modified residuei | 161 | Omega-N-methylarginineCombined sources | 1 | |
Modified residuei | 191 | Omega-N-methylarginineCombined sources | 1 | |
Modified residuei | 213 | PhosphoserineCombined sources | 1 | |
Modified residuei | 223 | PhosphoserineCombined sources | 1 | |
Modified residuei | 239 | PhosphoserineCombined sources | 1 | |
Modified residuei | 243 | PhosphoserineCombined sources | 1 | |
Modified residuei | 245 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 247 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 253 | PhosphoserineCombined sources | 1 | |
Modified residuei | 257 | PhosphoserineCombined sources | 1 | |
Modified residuei | 295 | PhosphoserineBy similarity | 1 | |
Modified residuei | 299 | PhosphoserineCombined sources | 1 | |
Modified residuei | 416 | PhosphoserineCombined sources | 1 | |
Modified residuei | 420 | PhosphoserineCombined sources | 1 | |
Modified residuei | 422 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 428 | PhosphoserineCombined sources | 1 | |
Modified residuei | 436 | PhosphothreonineCombined sources | 1 | |
Modified residuei | 441 | PhosphoserineCombined sources | 1 | |
Modified residuei | 445 | PhosphoserineCombined sources | 1 | |
Modified residuei | 459 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Keywords - PTMi
Acetylation, Methylation, PhosphoproteinProteomic databases
EPDi | P85037 |
jPOSTi | P85037 |
MassIVEi | P85037 |
MaxQBi | P85037 |
PaxDbi | P85037 |
PeptideAtlasi | P85037 |
PRIDEi | P85037 |
ProteomicsDBi | 57762 [P85037-1] 57763 [P85037-2] |
PTM databases
GlyGeni | P85037, 28 sites, 2 O-linked glycans (28 sites) |
iPTMneti | P85037 |
PhosphoSitePlusi | P85037 |
Expressioni
Tissue specificityi
Gene expression databases
Bgeei | ENSG00000164916, Expressed in cerebellar vermis and 226 other tissues |
ExpressionAtlasi | P85037, baseline and differential |
Genevisiblei | P85037, HS |
Organism-specific databases
HPAi | ENSG00000164916, Low tissue specificity |
Interactioni
Subunit structurei
Interacts with SIN3A and SIN3B (via PAH2) to form a complex which represses transcription (By similarity).
Component of SIN3A-, but not SIN3B-, containing multiprotein complexes (By similarity).
Interacts with FOXO4 and MEF2C; both interactions inhibit FOXO4 and MEF2C transactivation activity (By similarity).
Interacts (when phosphorylated) with YWHAE/14-3-3-epsilon; promotes sequestration in the cytoplasm and leads to impaired ability to bind DNA (By similarity).
Interacts with FHL2 (By similarity).
Interacts with SRF (PubMed:17670796).
Interacts with DVL2 and DVL3; the interaction induces DVL2 nuclear translocation (PubMed:25805136).
Interacts with BAP1 (when phosphorylated) (PubMed:25451922).
By similarity3 PublicationsBinary interactionsi
GO - Molecular functioni
- 14-3-3 protein binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 128769, 183 interactors |
IntActi | P85037, 111 interactors |
MINTi | P85037 |
STRINGi | 9606.ENSP00000328720 |
Miscellaneous databases
RNActi | P85037, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 123 – 175 | FHAPROSITE-ProRule annotationAdd BLAST | 53 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 2 – 40 | Interaction with SIN3A and SIN3BBy similarityAdd BLAST | 39 | |
Regioni | 36 – 79 | DisorderedSequence analysisAdd BLAST | 44 | |
Regioni | 95 – 420 | Required for interaction with FOXO4 and MEF2CBy similarityAdd BLAST | 326 | |
Regioni | 287 – 306 | DisorderedSequence analysisAdd BLAST | 20 | |
Regioni | 413 – 436 | DisorderedSequence analysisAdd BLAST | 24 | |
Regioni | 676 – 733 | DisorderedSequence analysisAdd BLAST | 58 |
Compositional bias
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Compositional biasi | 36 – 64 | Pro residuesSequence analysisAdd BLAST | 29 | |
Compositional biasi | 679 – 700 | Polar residuesSequence analysisAdd BLAST | 22 |
Phylogenomic databases
eggNOGi | KOG2294, Eukaryota |
GeneTreei | ENSGT00940000159507 |
HOGENOMi | CLU_022344_0_0_1 |
InParanoidi | P85037 |
OMAi | VTIGQHH |
OrthoDBi | 1270467at2759 |
PhylomeDBi | P85037 |
TreeFami | TF325718 |
Family and domain databases
CDDi | cd00059, FH, 1 hit cd00060, FHA, 1 hit |
Gene3Di | 1.10.10.10, 1 hit |
InterProi | View protein in InterPro IPR000253, FHA_dom IPR001766, Fork_head_dom IPR008984, SMAD_FHA_dom_sf IPR018122, TF_fork_head_CS_1 IPR030456, TF_fork_head_CS_2 IPR036388, WH-like_DNA-bd_sf IPR036390, WH_DNA-bd_sf |
Pfami | View protein in Pfam PF00498, FHA, 1 hit PF00250, Forkhead, 1 hit |
PRINTSi | PR00053, FORKHEAD |
SMARTi | View protein in SMART SM00339, FH, 1 hit SM00240, FHA, 1 hit |
SUPFAMi | SSF46785, SSF46785, 1 hit SSF49879, SSF49879, 1 hit |
PROSITEi | View protein in PROSITE PS50006, FHA_DOMAIN, 1 hit PS00657, FORK_HEAD_1, 1 hit PS00658, FORK_HEAD_2, 1 hit PS50039, FORK_HEAD_3, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
: The displayed sequence is further processed into a mature form. Sequence processingi
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MAEVGEDSGA RALLALRSAP CSPVLCAAAA AAAFPAAAPP PAPAQPQPPP
60 70 80 90 100
GPPPPPPPPL PPGAIAGAGS SGGSSGVSGD SAVAGAAPAL VAAAAASVRQ
110 120 130 140 150
SPGPALARLE GREFEFLMRQ PSVTIGRNSS QGSVDLSMGL SSFISRRHLQ
160 170 180 190 200
LSFQEPHFYL RCLGKNGVFV DGAFQRRGAP ALQLPKQCTF RFPSTAIKIQ
210 220 230 240 250
FTSLYHKEEA PASPLRPLYP QISPLKIHIP EPDLRSMVSP VPSPTGTISV
260 270 280 290 300
PNSCPASPRG AGSSSYRFVQ NVTSDLQLAA EFAAKAASEQ QADTSGGDSP
310 320 330 340 350
KDESKPPFSY AQLIVQAISS AQDRQLTLSG IYAHITKHYP YYRTADKGWQ
360 370 380 390 400
NSIRHNLSLN RYFIKVPRSQ EEPGKGSFWR IDPASEAKLV EQAFRKRRQR
410 420 430 440 450
GVSCFRTPFG PLSSRSAPAS PTHPGLMSPR SGGLQTPECL SREGSPIPHD
460 470 480 490 500
PEFGSKLASV PEYRYSQSAP GSPVSAQPVI MAVPPRPSSL VAKPVAYMPA
510 520 530 540 550
SIVTSQQPAG HAIHVVQQAP TVTMVRVVTT SANSANGYIL TSQGAAGGSH
560 570 580 590 600
DAAGAAVLDL GSEARGLEEK PTIAFATIPA AGGVIQTVAS QMAPGVPGHT
610 620 630 640 650
VTILQPATPV TLGQHHLPVR AVTQNGKHAV PTNSLAGNAY ALTSPLQLLA
660 670 680 690 700
TQASSSAPVV VTRVCEVGPK EPAAAVAATA TTTPATATTA SASASSTGEP
710 720 730
EVKRSRVEEP SGAVTTPAGV IAAAGPQGPG TGE
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketU3KQ26 | U3KQ26_HUMAN | Forkhead box protein K1 | FOXK1 | 109 | Annotation score: |
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 144 | I → V in CB959941 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 154 – 155 | QE → KS in CB959941 (PubMed:15489334).Curated | 2 | |
Sequence conflicti | 159 | Y → S in CB959941 (PubMed:15489334).Curated | 1 | |
Sequence conflicti | 217 | P → A in AW206906 (Ref. 4) Curated | 1 | |
Sequence conflicti | 232 | P → T in AW206906 (Ref. 4) Curated | 1 | |
Sequence conflicti | 437 – 445 | Missing in AK122663 (PubMed:14702039).Curated | 9 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_052239 | 1 – 163 | Missing in isoform 2. 2 PublicationsAdd BLAST | 163 | |
Alternative sequenceiVSP_052240 | 164 – 187 | GKNGV…QLPKQ → MAYCLGVNFVPSRFCYQLHR LLLR in isoform 2. 2 PublicationsAdd BLAST | 24 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK122663 mRNA No translation available. AC072054 Genomic DNA No translation available. AC092428 Genomic DNA No translation available. AC092610 Genomic DNA No translation available. BC038434 mRNA No translation available. CB959941 mRNA No translation available. AW206906 mRNA No translation available. |
CCDSi | CCDS34591.1 [P85037-1] |
RefSeqi | NP_001032242.1, NM_001037165.1 [P85037-1] XP_011513493.1, XM_011515191.2 |
Genome annotation databases
Ensembli | ENST00000328914.5; ENSP00000328720.4; ENSG00000164916.11 |
GeneIDi | 221937 |
KEGGi | hsa:221937 |
MANE-Selecti | ENST00000328914.5; ENSP00000328720.4; NM_001037165.2; NP_001032242.1 |
UCSCi | uc003snc.2, human [P85037-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AK122663 mRNA No translation available. AC072054 Genomic DNA No translation available. AC092428 Genomic DNA No translation available. AC092610 Genomic DNA No translation available. BC038434 mRNA No translation available. CB959941 mRNA No translation available. AW206906 mRNA No translation available. |
CCDSi | CCDS34591.1 [P85037-1] |
RefSeqi | NP_001032242.1, NM_001037165.1 [P85037-1] XP_011513493.1, XM_011515191.2 |
3D structure databases
AlphaFoldDBi | P85037 |
BMRBi | P85037 |
SMRi | P85037 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 128769, 183 interactors |
IntActi | P85037, 111 interactors |
MINTi | P85037 |
STRINGi | 9606.ENSP00000328720 |
PTM databases
GlyGeni | P85037, 28 sites, 2 O-linked glycans (28 sites) |
iPTMneti | P85037 |
PhosphoSitePlusi | P85037 |
Genetic variation databases
BioMutai | FOXK1 |
DMDMi | 118572324 |
Proteomic databases
EPDi | P85037 |
jPOSTi | P85037 |
MassIVEi | P85037 |
MaxQBi | P85037 |
PaxDbi | P85037 |
PeptideAtlasi | P85037 |
PRIDEi | P85037 |
ProteomicsDBi | 57762 [P85037-1] 57763 [P85037-2] |
Protocols and materials databases
Antibodypediai | 11250, 221 antibodies from 30 providers |
DNASUi | 221937 |
Genome annotation databases
Ensembli | ENST00000328914.5; ENSP00000328720.4; ENSG00000164916.11 |
GeneIDi | 221937 |
KEGGi | hsa:221937 |
MANE-Selecti | ENST00000328914.5; ENSP00000328720.4; NM_001037165.2; NP_001032242.1 |
UCSCi | uc003snc.2, human [P85037-1] |
Organism-specific databases
CTDi | 221937 |
DisGeNETi | 221937 |
GeneCardsi | FOXK1 |
HGNCi | HGNC:23480, FOXK1 |
HPAi | ENSG00000164916, Low tissue specificity |
MIMi | 616302, gene |
neXtProti | NX_P85037 |
OpenTargetsi | ENSG00000164916 |
PharmGKBi | PA134978307 |
VEuPathDBi | HostDB:ENSG00000164916 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2294, Eukaryota |
GeneTreei | ENSGT00940000159507 |
HOGENOMi | CLU_022344_0_0_1 |
InParanoidi | P85037 |
OMAi | VTIGQHH |
OrthoDBi | 1270467at2759 |
PhylomeDBi | P85037 |
TreeFami | TF325718 |
Enzyme and pathway databases
PathwayCommonsi | P85037 |
Reactomei | R-HSA-5689603, UCH proteinases |
SignaLinki | P85037 |
Miscellaneous databases
BioGRID-ORCSi | 221937, 98 hits in 1117 CRISPR screens |
ChiTaRSi | FOXK1, human |
GeneWikii | FOXK1 |
GenomeRNAii | 221937 |
Pharosi | P85037, Tbio |
PROi | PR:P85037 |
RNActi | P85037, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000164916, Expressed in cerebellar vermis and 226 other tissues |
ExpressionAtlasi | P85037, baseline and differential |
Genevisiblei | P85037, HS |
Family and domain databases
CDDi | cd00059, FH, 1 hit cd00060, FHA, 1 hit |
Gene3Di | 1.10.10.10, 1 hit |
InterProi | View protein in InterPro IPR000253, FHA_dom IPR001766, Fork_head_dom IPR008984, SMAD_FHA_dom_sf IPR018122, TF_fork_head_CS_1 IPR030456, TF_fork_head_CS_2 IPR036388, WH-like_DNA-bd_sf IPR036390, WH_DNA-bd_sf |
Pfami | View protein in Pfam PF00498, FHA, 1 hit PF00250, Forkhead, 1 hit |
PRINTSi | PR00053, FORKHEAD |
SMARTi | View protein in SMART SM00339, FH, 1 hit SM00240, FHA, 1 hit |
SUPFAMi | SSF46785, SSF46785, 1 hit SSF49879, SSF49879, 1 hit |
PROSITEi | View protein in PROSITE PS50006, FHA_DOMAIN, 1 hit PS00657, FORK_HEAD_1, 1 hit PS00658, FORK_HEAD_2, 1 hit PS50039, FORK_HEAD_3, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | FOXK1_HUMAN | |
Accessioni | P85037Primary (citable) accession number: P85037 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 28, 2006 |
Last sequence update: | November 28, 2006 | |
Last modified: | May 25, 2022 | |
This is version 152 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- Human chromosome 7
Human chromosome 7: entries, gene names and cross-references to MIM - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot