FOXK2_XENLA
ID FOXK2_XENLA Reviewed; 642 AA.
AC Q7ZX03; Q2KHQ1;
DT 28-NOV-2006, integrated into UniProtKB/Swiss-Prot.
DT 28-NOV-2006, sequence version 2.
DT 03-AUG-2022, entry version 93.
DE RecName: Full=Forkhead box protein K2;
DE Short=FoxK2;
DE AltName: Full=Interleukin enhancer-binding factor 1;
DE Short=ILF1;
DE Short=xFoxK1 {ECO:0000303|PubMed:14986136};
GN Name=foxk2 {ECO:0000250|UniProtKB:Q01167};
GN Synonyms=foxk1 {ECO:0000303|PubMed:14986136},
GN ilf1 {ECO:0000312|EMBL:AAH46369.1};
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1] {ECO:0000312|EMBL:AAH46369.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain {ECO:0000312|EMBL:AAI12950.1}, and
RC Embryo {ECO:0000312|EMBL:AAH46369.1};
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-638, TISSUE SPECIFICITY, AND DEVELOPMENTAL
RP STAGE.
RC TISSUE=Tadpole;
RX PubMed=14986136; DOI=10.1007/s00427-004-0391-7;
RA Pohl B.S., Knoechel W.;
RT "Isolation and developmental expression of Xenopus FoxJ1 and FoxK1.";
RL Dev. Genes Evol. 214:200-205(2004).
RN [3]
RP REVIEW.
RX PubMed=15656969; DOI=10.1016/j.gene.2004.09.037;
RA Pohl B.S., Knoechel W.;
RT "Of fox and frogs: fox (fork head/winged helix) transcription factors in
RT Xenopus development.";
RL Gene 344:21-32(2005).
CC -!- FUNCTION: Transcriptional regulator involved in different processes
CC such as glucose metabolism, aerobic glycolysis and autophagy (By
CC similarity). Recognizes and binds the forkhead DNA sequence motif (5'-
CC GTAAACA-3') and can both act as a transcription activator or repressor,
CC depending on the context (By similarity). Acts as a key regulator of
CC metabolic reprogramming towards aerobic glycolysis, a process in which
CC glucose is converted to lactate in the presence of oxygen. Acts as a
CC negative regulator of autophagy in skeletal muscle: in response to
CC starvation, enters the nucleus, binds the promoters of autophagy genes
CC and represses their expression, preventing proteolysis of skeletal
CC muscle proteins (By similarity). {ECO:0000250|UniProtKB:Q01167,
CC ECO:0000250|UniProtKB:Q3UCQ1}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q01167}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q3UCQ1}.
CC -!- TISSUE SPECIFICITY: In neurula embryos, expressed strongly in the
CC future floor plate and weakly in the neural crest progenitor cells. As
CC development progresses, expression becomes stronger in neural crest
CC cells. At stage 24, expressed in the eye, brain, branchial arches and
CC in the presomitic mesoderm in the posterior embryo. At stage 29,
CC additionally expressed in the pronephric tubules. At stage 35,
CC expressed in the migrating lateral muscle precursors of the abdomen.
CC Additionally, the developing proctodeum and head structures including
CC the branchial arches, eyes and otic vesicles continue to show
CC expression. Expression also persists in the nephros.
CC {ECO:0000269|PubMed:14986136}.
CC -!- DEVELOPMENTAL STAGE: Expressed both maternally and zygotically.
CC Expressed throughout all embryonic stages. Maternal expression persists
CC during early cleavage stages. Expression levels decrease at the onset
CC of gastrulation, increase at the start of neurulation and are then
CC maintained throughout future embryonic stages.
CC {ECO:0000269|PubMed:14986136}.
CC -!- DOMAIN: The C-terminal part of the DNA-binding domain may contribute to
CC DNA recognition specificity. {ECO:0000250|UniProtKB:Q01167}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH46369.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Potential poly-A sequence.; Evidence={ECO:0000305};
CC Sequence=AAI12950.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; BC046369; AAH46369.1; ALT_SEQ; mRNA.
DR EMBL; BC112949; AAI12950.1; ALT_SEQ; mRNA.
DR AlphaFoldDB; Q7ZX03; -.
DR BMRB; Q7ZX03; -.
DR SMR; Q7ZX03; -.
DR IntAct; Q7ZX03; 1.
DR Proteomes; UP000186698; Genome assembly.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003677; F:DNA binding; NAS:UniProtKB.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:UniProtKB.
DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; ISS:UniProtKB.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISS:UniProtKB.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISS:UniProtKB.
DR GO; GO:0061621; P:canonical glycolysis; ISS:UniProtKB.
DR GO; GO:0001678; P:cellular glucose homeostasis; ISS:UniProtKB.
DR GO; GO:0010507; P:negative regulation of autophagy; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0010906; P:regulation of glucose metabolic process; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; NAS:UniProtKB.
DR GO; GO:0042594; P:response to starvation; ISS:UniProtKB.
DR CDD; cd00059; FH; 1.
DR CDD; cd00060; FHA; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR InterPro; IPR000253; FHA_dom.
DR InterPro; IPR001766; Fork_head_dom.
DR InterPro; IPR008984; SMAD_FHA_dom_sf.
DR InterPro; IPR018122; TF_fork_head_CS_1.
DR InterPro; IPR030456; TF_fork_head_CS_2.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR InterPro; IPR036390; WH_DNA-bd_sf.
DR Pfam; PF00498; FHA; 1.
DR Pfam; PF00250; Forkhead; 1.
DR PRINTS; PR00053; FORKHEAD.
DR SMART; SM00339; FH; 1.
DR SMART; SM00240; FHA; 1.
DR SUPFAM; SSF46785; SSF46785; 1.
DR SUPFAM; SSF49879; SSF49879; 1.
DR PROSITE; PS50006; FHA_DOMAIN; 1.
DR PROSITE; PS00657; FORK_HEAD_1; 1.
DR PROSITE; PS00658; FORK_HEAD_2; 1.
DR PROSITE; PS50039; FORK_HEAD_3; 1.
PE 2: Evidence at transcript level;
KW Activator; Cytoplasm; DNA-binding; Magnesium; Metal-binding; Nucleus;
KW Reference proteome; Repressor; Transcription; Transcription regulation.
FT CHAIN 1..642
FT /note="Forkhead box protein K2"
FT /id="PRO_0000262763"
FT DOMAIN 30..91
FT /note="FHA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00086"
FT DNA_BIND 219..314
FT /note="Fork-head"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT REGION 201..221
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 261..279
FT /note="DNA-binding; major groove"
FT /evidence="ECO:0000250|UniProtKB:Q01167"
FT REGION 289..293
FT /note="DNA-binding; minor groove"
FT /evidence="ECO:0000250|UniProtKB:Q01167"
FT REGION 309..314
FT /note="DNA-binding; minor groove"
FT /evidence="ECO:0000250|UniProtKB:Q01167"
FT REGION 323..359
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 589..615
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 327..356
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 271
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q01167"
FT BINDING 272
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q01167"
FT BINDING 274
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q01167"
FT BINDING 277
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:Q01167"
FT CONFLICT 266
FT /note="S -> P (in Ref. 1; AAI12950)"
FT /evidence="ECO:0000305"
FT CONFLICT 577
FT /note="A -> AA (in Ref. 1; AAI12950)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 642 AA; 68969 MW; C9DD4765003CD0E1 CRC64;
MAVAVCGAVV PVVARLEGRE FEYLMKKRSV TIGRNSSQGC VDVSMGHSSF ISRRHLEIFI
GGSGDGDDAD VGDFYLRCLG KNGVFVDGVF QRRGAPPLQL PRVCTFRFPS TNIKITFTAL
AIDKKQKLEA PESPVKPVQP QISPLTIHIP DNIAHLISPL PSPTGTISAA NSCPSSPRGA
GSSGFKFGRV IPPDLIAEAA QSENDKDASG GDSPKDDSKP PYSYAQLIVQ AITMAPDKQL
TLNGIYTHIT KNYPYYRTAD KGWQNSIRHN LSLNRYFIKV PRSQEEPGKG SFWRIDPASE
SKLVEQAFRK RRPRGVPCFR TPLGPLSSRS APASPNHSGV FSAHSSGVQT PESLSREGSP
IPLEPDASVI HPKLAVIQEA RFAQSAPGSP LSSQPVLITV QRQLPQTIKP VTYTVAAPVT
TATSQQAVMQ TVHVVHQIPA VSVTNVTGLT PINTYTVGGQ TMVAQAAVMA QPKLEHQENG
DHKEVKVKVE AIPAIGHPAL TTASRIIQTS SSAPLQTVTI VQTPLGQHQL PIKAVTQNGT
HVVPITTAIQ GQVTTANSSY SLIESPWQWR GNGTRAASPL HMLATHASAS ASLPTKRQNG
DQSEQPDIKR GKTDEREVLA MTGLDAQSEM AMAASNEQEN QK
