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FKH9_CAEEL
ID   FKH9_CAEEL              Reviewed;         300 AA.
AC   Q21187; Q2L6X6; Q7Z136;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-2002, sequence version 2.
DT   03-AUG-2022, entry version 175.
DE   RecName: Full=Forkhead transcription factor fkh-9 {ECO:0000312|WormBase:K03C7.2a};
GN   Name=fkh-9 {ECO:0000312|WormBase:K03C7.2a};
GN   ORFNames=K03C7.2 {ECO:0000312|WormBase:K03C7.2a};
OS   Caenorhabditis elegans.
OC   Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC   Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC   Caenorhabditis.
OX   NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN   [1] {ECO:0000312|Proteomes:UP000001940}
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
RX   PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG   The C. elegans sequencing consortium;
RT   "Genome sequence of the nematode C. elegans: a platform for investigating
RT   biology.";
RL   Science 282:2012-2018(1998).
RN   [2] {ECO:0000305}
RP   FUNCTION.
RX   PubMed=26963674; DOI=10.1016/j.ydbio.2016.02.031;
RA   Goszczynski B., Captan V.V., Danielson A.M., Lancaster B.R., McGhee J.D.;
RT   "A 44 bp intestine-specific hermaphrodite-specific enhancer from the C.
RT   elegans vit-2 vitellogenin gene is directly regulated by ELT-2, MAB-3, FKH-
RT   9 and DAF-16 and indirectly regulated by the germline, by daf-2/insulin
RT   signaling and by the TGF-beta/Sma/Mab pathway.";
RL   Dev. Biol. 413:112-127(2016).
RN   [3] {ECO:0000305}
RP   FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP   PHENOTYPE.
RX   PubMed=26675724; DOI=10.1038/nature16483;
RA   Kaletsky R., Lakhina V., Arey R., Williams A., Landis J., Ashraf J.,
RA   Murphy C.T.;
RT   "The C. elegans adult neuronal IIS/FOXO transcriptome reveals adult
RT   phenotype regulators.";
RL   Nature 529:92-96(2016).
RN   [4] {ECO:0000305}
RP   FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF
RP   GLY-111.
RX   PubMed=30287474; DOI=10.1534/genetics.118.301450;
RA   Tillman E.J., Richardson C.E., Cattie D.J., Reddy K.C., Lehrbach N.J.,
RA   Droste R., Ruvkun G., Kim D.H.;
RT   "Endoplasmic Reticulum Homeostasis Is Modulated by the Forkhead
RT   Transcription Factor FKH-9 During Infection of Caenorhabditis elegans.";
RL   Genetics 210:1329-1337(2018).
CC   -!- FUNCTION: Transcription factor (PubMed:26963674). Binds to the
CC       regulatory elements of genes that contain the sequence motif 5'-
CC       TTGTTTCT-3' (PubMed:26963674). Involved in regulating intestinal
CC       transcription of vitellogenin vit-2, acting in concert with
CC       transcription factors elt-2, mab-3 and daf-16, and also the TGF-
CC       beta/Sma/Mab pathway (PubMed:26963674). Functions downstream of the
CC       insulin/IGF-1-like signaling (IIS) mediated pathway, in regeneration of
CC       axons after injury and in short-term memory, perhaps acting in neurons,
CC       and in modulation of longevity, perhaps acting non-neuronally
CC       (PubMed:26675724). Plays a role in the modulation of endoplasmic
CC       reticulum (ER) homeostasis during chemical and pathogen stress,
CC       including exposure to the Gram-negative bacterium P.aeruginosa
CC       (PubMed:30287474). {ECO:0000269|PubMed:26675724,
CC       ECO:0000269|PubMed:26963674, ECO:0000269|PubMed:30287474}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00089,
CC       ECO:0000269|PubMed:26675724, ECO:0000269|PubMed:30287474}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=a {ECO:0000312|WormBase:K03C7.2a};
CC         IsoId=Q21187-1; Sequence=Displayed;
CC       Name=b {ECO:0000312|WormBase:K03C7.2b};
CC         IsoId=Q21187-2; Sequence=VSP_061276;
CC       Name=c {ECO:0000312|WormBase:K03C7.2c};
CC         IsoId=Q21187-3; Sequence=VSP_061275;
CC   -!- TISSUE SPECIFICITY: Expressed in mechanosensory neurons.
CC       {ECO:0000269|PubMed:26675724}.
CC   -!- DEVELOPMENTAL STAGE: Expressed in neurons and intestinal cells in L2
CC       stage larvae. {ECO:0000269|PubMed:30287474}.
CC   -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown severely impairs axon
CC       regeneration in a daf-2 mutant background, in a daf-16-dependent-manner
CC       (PubMed:26675724). Impairs short-term associative memory in a daf-2
CC       mutant background in a daf-16-dependent-manner (PubMed:26675724).
CC       Reduces longevity in a daf-2 mutant background (PubMed:26675724).
CC       {ECO:0000269|PubMed:26675724}.
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DR   EMBL; BX284606; CCD70485.1; -; Genomic_DNA.
DR   EMBL; BX284606; CCD70486.1; -; Genomic_DNA.
DR   EMBL; BX284606; CCD70487.1; -; Genomic_DNA.
DR   PIR; T16544; T16544.
DR   RefSeq; NP_001024760.1; NM_001029589.3.
DR   AlphaFoldDB; Q21187; -.
DR   SMR; Q21187; -.
DR   STRING; 6239.K03C7.2a; -.
DR   PaxDb; Q21187; -.
DR   PeptideAtlas; Q21187; -.
DR   EnsemblMetazoa; K03C7.2a.1; K03C7.2a.1; WBGene00001441. [Q21187-1]
DR   EnsemblMetazoa; K03C7.2b.1; K03C7.2b.1; WBGene00001441. [Q21187-2]
DR   EnsemblMetazoa; K03C7.2c.1; K03C7.2c.1; WBGene00001441. [Q21187-3]
DR   EnsemblMetazoa; K03C7.2c.2; K03C7.2c.2; WBGene00001441. [Q21187-3]
DR   EnsemblMetazoa; K03C7.2c.3; K03C7.2c.3; WBGene00001441. [Q21187-3]
DR   EnsemblMetazoa; K03C7.2c.4; K03C7.2c.4; WBGene00001441. [Q21187-3]
DR   GeneID; 180670; -.
DR   KEGG; cel:CELE_K03C7.2; -.
DR   UCSC; K03C7.2a; c. elegans. [Q21187-1]
DR   CTD; 180670; -.
DR   WormBase; K03C7.2a; CE31196; WBGene00001441; fkh-9.
DR   WormBase; K03C7.2b; CE34332; WBGene00001441; fkh-9.
DR   WormBase; K03C7.2c; CE39581; WBGene00001441; fkh-9.
DR   eggNOG; KOG2294; Eukaryota.
DR   HOGENOM; CLU_998283_0_0_1; -.
DR   InParanoid; Q21187; -.
DR   OMA; LASTIQM; -.
DR   OrthoDB; 1430006at2759; -.
DR   Reactome; R-CEL-9018519; Estrogen-dependent gene expression.
DR   Proteomes; UP000001940; Chromosome X.
DR   Bgee; WBGene00001441; Expressed in larva and 3 other tissues.
DR   ExpressionAtlas; Q21187; baseline and differential.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IMP:UniProtKB.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR   GO; GO:0009653; P:anatomical structure morphogenesis; IBA:GO_Central.
DR   GO; GO:0031103; P:axon regeneration; IGI:WormBase.
DR   GO; GO:0030154; P:cell differentiation; IBA:GO_Central.
DR   GO; GO:0098542; P:defense response to other organism; IGI:UniProtKB.
DR   GO; GO:0008340; P:determination of adult lifespan; IGI:WormBase.
DR   GO; GO:0036503; P:ERAD pathway; IMP:UniProtKB.
DR   GO; GO:0007612; P:learning; IGI:WormBase.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR   GO; GO:0010498; P:proteasomal protein catabolic process; IMP:UniProtKB.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR   GO; GO:0034976; P:response to endoplasmic reticulum stress; IGI:UniProtKB.
DR   GO; GO:0007614; P:short-term memory; IGI:WormBase.
DR   CDD; cd00059; FH; 1.
DR   Gene3D; 1.10.10.10; -; 1.
DR   InterPro; IPR001766; Fork_head_dom.
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; PF00250; Forkhead; 1.
DR   PRINTS; PR00053; FORKHEAD.
DR   SMART; SM00339; FH; 1.
DR   SUPFAM; SSF46785; SSF46785; 1.
DR   PROSITE; PS00658; FORK_HEAD_2; 1.
DR   PROSITE; PS50039; FORK_HEAD_3; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; DNA-binding; Nucleus; Reference proteome.
FT   CHAIN           1..300
FT                   /note="Forkhead transcription factor fkh-9"
FT                   /id="PRO_0000454295"
FT   DNA_BIND        66..161
FT                   /note="Fork-head"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00089"
FT   REGION          153..208
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        153..179
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        180..194
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         1..206
FT                   /note="Missing (in isoform c)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_061275"
FT   VAR_SEQ         1..20
FT                   /note="Missing (in isoform b)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_061276"
FT   MUTAGEN         111
FT                   /note="G->E: In qd197; suppresses larval lethality and
FT                   defects in the endoplasmic reticulum (ER) in an xbp-1
FT                   mutant background, when exposed to the Gram-negative
FT                   bacterium P.aeruginosa. Enhances resistance to tunicamycin,
FT                   probably as a result of enhanced ER stress resistance.
FT                   Enhances sensitivity to proteasome inhibition."
FT                   /evidence="ECO:0000269|PubMed:30287474"
SQ   SEQUENCE   300 AA;  33345 MW;  EF24FBC0FB4D8FA0 CRC64;
     MCSTMTATMN QTICEKQNIT MDLLRSPIQI PSASDTIKIE TPSTISSQPS PIQTPLAAAS
     SDNFERPSLS YKDLIIEAID RSPEKRLKLN EIYQVIRLLH PYYRHRPDQW GWQNSIRHNL
     SLHDCFVKLP LKQTSASGVV GHFWTVVPEL SDKQTLRRRN RQQPRALAKK SDAGRTLSRD
     DRGSSGSGET SPSPSQPSIS PPNENPMPSV QALNVLELLS GMNDYKGTLF QNNYRTNLIQ
     DNSAVNGLQN LLTTTLMQIN PQLGALLSLA NLNNLTTNQL QIASPSLSPI KAESQSFLLQ
 
 
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