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EGL46_CAEEL
ID   EGL46_CAEEL             Reviewed;         286 AA.
AC   G5EFY4;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   14-DEC-2011, sequence version 1.
DT   03-AUG-2022, entry version 85.
DE   RecName: Full=Transcription factor egl-46 {ECO:0000305};
DE   AltName: Full=Egg-laying defective protein 46 {ECO:0000312|WormBase:K11G9.4};
GN   Name=egl-46 {ECO:0000312|WormBase:K11G9.4};
GN   ORFNames=K11G9.4 {ECO:0000312|WormBase:K11G9.4};
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:0000312|EMBL:AAG13398.1}
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA   Wu J., Duggan A., Chalfie M.;
RT   "Inhibition of Touch Cell Fate in C. elegans.";
RL   Submitted (JUN-2000) to the EMBL/GenBank/DDBJ databases.
RN   [3] {ECO:0000305}
RP   FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP   AND MUTAGENESIS OF CYS-200.
RX   PubMed=11274062; DOI=10.1101/gad.857401;
RA   Wu J., Duggan A., Chalfie M.;
RT   "Inhibition of touch cell fate by egl-44 and egl-46 in C. elegans.";
RL   Genes Dev. 15:789-802(2001).
RN   [4] {ECO:0000305}
RP   FUNCTION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF 55-TRP--MET-286.
RX   PubMed=12954713; DOI=10.1242/dev.00678;
RA   Yu H., Pretot R.F., Burglin T.R., Sternberg P.W.;
RT   "Distinct roles of transcription factors EGL-46 and DAF-19 in specifying
RT   the functionality of a polycystin-expressing sensory neuron necessary for
RT   C. elegans male vulva location behavior.";
RL   Development 130:5217-5227(2003).
RN   [5] {ECO:0000305}
RP   FUNCTION.
RX   PubMed=20923979; DOI=10.1534/genetics.110.122879;
RA   Wang J., Schwartz H.T., Barr M.M.;
RT   "Functional specialization of sensory cilia by an RFX transcription factor
RT   isoform.";
RL   Genetics 186:1295-1307(2010).
RN   [6] {ECO:0000305}
RP   FUNCTION, INTERACTION WITH EGL-44, SUBCELLULAR LOCATION, DEVELOPMENTAL
RP   STAGE, AND MUTAGENESIS OF 101-GLN--MET-286.
RX   PubMed=23946438; DOI=10.1242/dev.098723;
RA   Feng G., Yi P., Yang Y., Chai Y., Tian D., Zhu Z., Liu J., Zhou F.,
RA   Cheng Z., Wang X., Li W., Ou G.;
RT   "Developmental stage-dependent transcriptional regulatory pathways control
RT   neuroblast lineage progression.";
RL   Development 140:3838-3847(2013).
RN   [7] {ECO:0000305}
RP   FUNCTION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF 117-ARG--MET-286.
RX   PubMed=25395666; DOI=10.1534/genetics.114.172049;
RA   Rojo Romanos T., Petersen J.G., Riveiro A.R., Pocock R.;
RT   "A novel role for the zinc-finger transcription factor EGL-46 in the
RT   differentiation of gas-sensing neurons in Caenorhabditis elegans.";
RL   Genetics 199:157-163(2015).
RN   [8] {ECO:0000305}
RP   FUNCTION.
RX   PubMed=29031632; DOI=10.1016/j.ydbio.2017.10.009;
RA   O'Brien B.M.J., Palumbos S.D., Novakovic M., Shang X., Sundararajan L.,
RA   Miller D.M. III;
RT   "Separate transcriptionally regulated pathways specify distinct classes of
RT   sister dendrites in a nociceptive neuron.";
RL   Dev. Biol. 432:248-257(2017).
RN   [9] {ECO:0000305}
RP   FUNCTION, AND INTERACTION WITH EGL-44.
RX   PubMed=30291162; DOI=10.1242/dev.168096;
RA   Zheng C., Jin F.Q., Trippe B.L., Wu J., Chalfie M.;
RT   "Inhibition of cell fate repressors secures the differentiation of the
RT   touch receptor neurons of Caenorhabditis elegans.";
RL   Development 145:0-0(2018).
CC   -!- FUNCTION: Transcription factor (PubMed:30291162). Represses expression
CC       of genes involved in differentiation of touch receptor neurons (TRN),
CC       probably acting as a heterodimer with egl-44, perhaps by occupying
CC       similar cis-regulatory elements as an unc-86/mec-3 heterodimer
CC       (PubMed:30291162). Plays a role in cell fate specification of neurons,
CC       including the hook neuron HOB, the gas-sensing neuron BAG and touch
CC       receptor neurons (PubMed:12954713, PubMed:25395666, PubMed:30291162).
CC       Plays a role in neuron differentiation by repressing the expression of
CC       zag-1 in FLP neurons, probably acting as a heterodimer with egl-44;
CC       because zag-1 represses expression of egl-46 and egl-44, together these
CC       proteins form a bistable, negative-feedback loop that regulates the
CC       choice between neuronal fates (PubMed:30291162). Acts downstream of
CC       egl-44 to prevent touch cell differentiation in FLP neurons
CC       (PubMed:11274062). Involved in male mating behavior, acting in concert
CC       with egl-44, via modulation of expression of polycystins lov-1 and pkd-
CC       2, homeodomain protein ceh-26, and neuropeptide-like protein nlp-8
CC       (PubMed:12954713). Modulates the expression of a subset of terminal
CC       differentiation genes involved in O(2)- and CO(2)-sensing, acting in
CC       parallel to ets-5 and egl-13 (PubMed:25395666). May act upstream of RFX
CC       transcription factor daf-19 to regulate gene expression specifically in
CC       the HOB neuron (PubMed:20923979). Plays a role in specifying
CC       commissural dendrites of the PVD nociceptive neurons, acting in concert
CC       with egl-44 (PubMed:29031632). In association with egl-44, regulates
CC       cell cycle exit in the neuronal Q cell lineage (PubMed:23946438).
CC       {ECO:0000269|PubMed:11274062, ECO:0000269|PubMed:12954713,
CC       ECO:0000269|PubMed:20923979, ECO:0000269|PubMed:23946438,
CC       ECO:0000269|PubMed:25395666, ECO:0000269|PubMed:29031632,
CC       ECO:0000269|PubMed:30291162}.
CC   -!- SUBUNIT: Interacts (via C-terminus) with egl-44 (via N-terminus); the
CC       interaction is direct; the interaction may regulate transcription.
CC       {ECO:0000269|PubMed:23946438, ECO:0000269|PubMed:30291162}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11274062,
CC       ECO:0000269|PubMed:23946438}. Note=Localized to nucleus during
CC       interphase and evenly distributed in the cytoplasm of dividing Q.a and
CC       Q.p neuroblasts. {ECO:0000269|PubMed:23946438}.
CC   -!- TISSUE SPECIFICITY: Expressed in touch cells, HSN cells, ventral cord
CC       motor neurons and ciliated ray neurons. {ECO:0000269|PubMed:11274062}.
CC   -!- DEVELOPMENTAL STAGE: Expressed in neuronal cells, initially in embryos
CC       after gastrulation, including ventral cord motor neurons during the L1
CC       larval stage, FLP, AVM and HSB neurons during L2, and PVM neurons
CC       during L3 (PubMed:11274062, PubMed:12954713). Expressed in the BAG
CC       neurons at the L2 and L3 stages of larval development
CC       (PubMed:25395666). Expressed in the HOB neuron beginning at the larval
CC       L4 stage and continuing throughout adulthood (PubMed:12954713).
CC       Expressed in the Q neuroblast lineage during larval development
CC       (PubMed:23946438, PubMed:11274062). {ECO:0000269|PubMed:11274062,
CC       ECO:0000269|PubMed:12954713, ECO:0000269|PubMed:23946438,
CC       ECO:0000269|PubMed:25395666}.
CC   -!- SIMILARITY: Belongs to the INSM1 family. {ECO:0000305}.
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DR   EMBL; AF283983; AAG13398.1; -; Genomic_DNA.
DR   EMBL; BX284605; CCD72926.1; -; Genomic_DNA.
DR   PIR; T29719; T29719.
DR   RefSeq; NP_504694.1; NM_072293.5.
DR   AlphaFoldDB; G5EFY4; -.
DR   STRING; 6239.K11G9.4; -.
DR   EPD; G5EFY4; -.
DR   PaxDb; G5EFY4; -.
DR   EnsemblMetazoa; K11G9.4.1; K11G9.4.1; WBGene00001210.
DR   GeneID; 179058; -.
DR   KEGG; cel:CELE_K11G9.4; -.
DR   CTD; 179058; -.
DR   WormBase; K11G9.4; CE07377; WBGene00001210; egl-46.
DR   eggNOG; KOG3993; Eukaryota.
DR   GeneTree; ENSGT00940000170254; -.
DR   HOGENOM; CLU_085484_0_0_1; -.
DR   InParanoid; G5EFY4; -.
DR   OMA; HKCPRIA; -.
DR   OrthoDB; 1194355at2759; -.
DR   PhylomeDB; G5EFY4; -.
DR   Proteomes; UP000001940; Chromosome V.
DR   Bgee; WBGene00001210; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR   GO; GO:0005634; C:nucleus; IDA:WormBase.
DR   GO; GO:0017053; C:transcription repressor complex; IBA:GO_Central.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; ISS:WormBase.
DR   GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IBA:GO_Central.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR   GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IPI:UniProtKB.
DR   GO; GO:0007411; P:axon guidance; IMP:WormBase.
DR   GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR   GO; GO:0045165; P:cell fate commitment; IMP:WormBase.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR   GO; GO:0055057; P:neuroblast division; IMP:WormBase.
DR   GO; GO:0030182; P:neuron differentiation; IMP:WormBase.
DR   GO; GO:0001764; P:neuron migration; IMP:WormBase.
DR   GO; GO:0031536; P:positive regulation of exit from mitosis; IMP:UniProtKB.
DR   GO; GO:0010564; P:regulation of cell cycle process; IBA:GO_Central.
DR   InterPro; IPR042972; INSM1/2.
DR   InterPro; IPR036236; Znf_C2H2_sf.
DR   InterPro; IPR013087; Znf_C2H2_type.
DR   PANTHER; PTHR15065; PTHR15065; 1.
DR   SUPFAM; SSF57667; SSF57667; 1.
DR   PROSITE; PS00028; ZINC_FINGER_C2H2_1; 1.
DR   PROSITE; PS50157; ZINC_FINGER_C2H2_2; 1.
PE   1: Evidence at protein level;
KW   Cell cycle; Differentiation; Metal-binding; Neurogenesis; Nucleus;
KW   Reference proteome; Repeat; Transcription; Transcription regulation; Zinc;
KW   Zinc-finger.
FT   CHAIN           1..286
FT                   /note="Transcription factor egl-46"
FT                   /id="PRO_0000454783"
FT   ZN_FING         180..200
FT                   /note="C2H2-type 1; atypical"
FT                   /evidence="ECO:0000305|PubMed:11274062"
FT   ZN_FING         208..230
FT                   /note="C2H2-type 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT   ZN_FING         248..271
FT                   /note="C2H2-type 3"
FT                   /evidence="ECO:0000305|PubMed:11274062"
FT   MUTAGEN         55..286
FT                   /note="Missing: In sy628; decreased mating efficiency in
FT                   males, as a result of deficiency in vulval location.
FT                   Abolishes expression of ceh-26, lov-1, and dramatically
FT                   reduces expression of pkd-2 and nlp-8, in the HOB neuron of
FT                   homozygous males. Has a mild egg-laying defect."
FT                   /evidence="ECO:0000269|PubMed:12954713"
FT   MUTAGEN         101..286
FT                   /note="Missing: In cas36; production of an extra neuron
FT                   from the Q lineage."
FT                   /evidence="ECO:0000269|PubMed:23946438"
FT   MUTAGEN         117..286
FT                   /note="Missing: In rp15; egg-laying defective and partial
FT                   loss of expression of guanylyl cyclase gcy-33."
FT                   /evidence="ECO:0000269|PubMed:25395666"
FT   MUTAGEN         200
FT                   /note="C->F: In n1126; defective hermaphrodite specific
FT                   neurons (HSN)."
FT                   /evidence="ECO:0000269|PubMed:11274062"
SQ   SEQUENCE   286 AA;  32473 MW;  D4CE138665A8B650 CRC64;
     MVPMNDFWVK AILSSTNPSP VPSTTSTVSN DENLDKTLDF DCSTQTVFPT LPMFWNPTLV
     QQMLALYQIQ QQQIQFSAKL APQPLFQEPT IQKEFLPFPH QSRKRPLPID PKKTKLRKLN
     EDTVTSSPVS GMFIKEEADV KSVEELQKEA DLLDETAAYV EVTEESRQKI DEIPNVIGDC
     ICRLCKVKYE DVFKLAQHKC PRIAHEEYKC PDCDKVFSCP ANLASHRRWH KPRNELGGSP
     PAQSSTIVSC STCFNSFPTK KMLKLHSSTC QRSPLQDLLS RVIPTM
 
 
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