TTX3_CAEEL
ID TTX3_CAEEL Reviewed; 409 AA.
AC G5EE86; B6VQ91;
DT 14-MAY-2014, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=LIM/homeobox protein ttx-3 {ECO:0000303|PubMed:9292724};
DE AltName: Full=Abnormal thermotaxis protein 3;
GN Name=ttx-3 {ECO:0000312|EMBL:CAB03956.3, ECO:0000312|WormBase:C40H5.5a};
GN ORFNames=C40H5.5;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1] {ECO:0000305, ECO:0000312|EMBL:AAB97099.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, SUBCELLULAR LOCATION,
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:AAB97099.1};
RX PubMed=9292724; DOI=10.1016/s0896-6273(00)80944-7;
RA Hobert O., Mori I., Yamashita Y., Honda H., Ohshima Y., Liu Y., Ruvkun G.;
RT "Regulation of interneuron function in the C. elegans thermoregulatory
RT pathway by the ttx-3 LIM homeobox gene.";
RL Neuron 19:345-357(1997).
RN [2] {ECO:0000312|EMBL:CAB03956.3}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:CAB03956.3};
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 [3] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF PHE-340.
RX PubMed=11493519; DOI=10.1242/dev.128.11.1951;
RA Altun-Gultekin Z., Andachi Y., Tsalik E.L., Pilgrim D., Kohara Y.,
RA Hobert O.;
RT "A regulatory cascade of three homeobox genes, ceh-10, ttx-3 and ceh-23,
RT controls cell fate specification of a defined interneuron class in C.
RT elegans.";
RL Development 128:1951-1969(2001).
RN [4] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16051801; DOI=10.1126/science.1114209;
RA Remy J.J., Hobert O.;
RT "An interneuronal chemoreceptor required for olfactory imprinting in C.
RT elegans.";
RL Science 309:787-790(2005).
RN [5] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=Bristol N2 {ECO:0000269|PubMed:21055415};
RX PubMed=21055415; DOI=10.1016/j.mad.2010.10.005;
RA Shen L., Hu Y., Cai T., Lin X., Wang D.;
RT "Regulation of longevity by genes required for the functions of AIY
RT interneuron in nematode Caenorhabditis elegans.";
RL Mech. Ageing Dev. 131:732-738(2010).
RN [6] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=24353061; DOI=10.1242/dev.099721;
RA Zhang F., Bhattacharya A., Nelson J.C., Abe N., Gordon P.,
RA Lloret-Fernandez C., Maicas M., Flames N., Mann R.S., Colon-Ramos D.A.,
RA Hobert O.;
RT "The LIM and POU homeobox genes ttx-3 and unc-86 act as terminal selectors
RT in distinct cholinergic and serotonergic neuron types.";
RL Development 141:422-435(2014).
CC -!- FUNCTION: Required for specification of the AIA and AIY interneurons
CC and the NSM neurons. Positively regulates the expression of a number of
CC genes including ceh-23, kal-1, hen-1, ser-2, unc-17 and sra-11 in AIY
CC interneurons and cat-4, flp-4, bas-1, ptps-1 and mgl-1 in NSM neurons.
CC Also acts in an autoregulatory feedback loop to maintain its own
CC expression. Plays a role in the thermotactic response, olfactory
CC imprinting, regulation of longevity, control of dauer formation and
CC axon outgrowth and pathfinding. Not required for normal chemosensory
CC behavior. {ECO:0000269|PubMed:11493519, ECO:0000269|PubMed:16051801,
CC ECO:0000269|PubMed:21055415, ECO:0000269|PubMed:24353061,
CC ECO:0000269|PubMed:9292724}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108,
CC ECO:0000269|PubMed:11493519, ECO:0000269|PubMed:9292724}. Perikaryon
CC {ECO:0000269|PubMed:11493519, ECO:0000269|PubMed:9292724}. Cell
CC projection, axon {ECO:0000269|PubMed:11493519,
CC ECO:0000269|PubMed:9292724}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=a {ECO:0000269|PubMed:9292724, ECO:0000269|PubMed:9851916};
CC IsoId=G5EE86-1; Sequence=Displayed;
CC Name=b {ECO:0000269|PubMed:9851916};
CC IsoId=G5EE86-2; Sequence=VSP_054579;
CC -!- TISSUE SPECIFICITY: Expressed in the AIA, AIN and AIY interneurons, and
CC in the NSM neurons. Expressed also in ADL and ASI sensory neurons in
CC 60-70% of L2 larvae. Expression is also detected in head muscles of
CC embryos and some early larvae but not late larvae or adults.
CC {ECO:0000269|PubMed:11493519, ECO:0000269|PubMed:24353061,
CC ECO:0000269|PubMed:9292724}.
CC -!- DEVELOPMENTAL STAGE: Expressed during embryogenesis and persists
CC through to adulthood in AIY interneurons. Expressed at L1 stage and
CC through adulthood in AIA and NSM neurons. Expression is detected in
CC head muscles of all 1.5 and 2-fold embryos, 47% of embryos just before
CC hatching and 6% of early larvae with no expression in head muscles of
CC late stage larvae or adults. {ECO:0000269|PubMed:11493519,
CC ECO:0000269|PubMed:24353061, ECO:0000269|PubMed:9292724}.
CC -!- DISRUPTION PHENOTYPE: Animals are cryophilic and move toward lower
CC temperatures irrespective of cultivation temperature in contrast to
CC wild-type animals which move toward their cultivation temperature when
CC placed on a temperature gradient. AIA and AIY interneurons display
CC defective neurite morphology. NSM neurons display loss of or reduced
CC expression of a number of terminal identity markers including cat-4,
CC flp-4, bas-1, ptps-1 and mgl-1. Reduced expression of ceh-23, kal-1,
CC C36B7.7, ser-2, unc-17 and sra-11 is observed in AIY interneurons.
CC Preexposure to odorants fails to leave an olfactory imprint. Mean
CC lifespan is reduced by 10% with decreased pharyngeal pumping and
CC increased intestinal autofluorescence caused by lysosomal deposits of
CC lipofuscin, indicative of cellular damage and aging. Formation of very
CC few dauers in starvation conditions. No defects observed in brood size,
CC egg number or chemotactic behavior toward volatile chemicals.
CC {ECO:0000269|PubMed:11493519, ECO:0000269|PubMed:16051801,
CC ECO:0000269|PubMed:21055415, ECO:0000269|PubMed:24353061,
CC ECO:0000269|PubMed:9292724}.
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DR EMBL; U72211; AAB97099.1; -; mRNA.
DR EMBL; Z81482; CAB03956.3; -; Genomic_DNA.
DR EMBL; Z81482; CAR97817.1; -; Genomic_DNA.
DR PIR; T19871; T19871.
DR RefSeq; NP_001257168.1; NM_001270239.1. [G5EE86-1]
DR RefSeq; NP_001257169.1; NM_001270240.1. [G5EE86-2]
DR AlphaFoldDB; G5EE86; -.
DR SMR; G5EE86; -.
DR BioGRID; 46265; 1.
DR STRING; 6239.C40H5.5a; -.
DR PaxDb; G5EE86; -.
DR EnsemblMetazoa; C40H5.5a.1; C40H5.5a.1; WBGene00006654. [G5EE86-1]
DR EnsemblMetazoa; C40H5.5b.1; C40H5.5b.1; WBGene00006654. [G5EE86-2]
DR GeneID; 181357; -.
DR KEGG; cel:CELE_C40H5.5; -.
DR CTD; 181357; -.
DR WormBase; C40H5.5a; CE27107; WBGene00006654; ttx-3. [G5EE86-1]
DR WormBase; C40H5.5b; CE43132; WBGene00006654; ttx-3. [G5EE86-2]
DR eggNOG; KOG0490; Eukaryota.
DR GeneTree; ENSGT00940000165771; -.
DR InParanoid; G5EE86; -.
DR OMA; MQINGRE; -.
DR OrthoDB; 1174930at2759; -.
DR PhylomeDB; G5EE86; -.
DR PRO; PR:G5EE86; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00006654; Expressed in pharyngeal muscle cell (C elegans) and 2 other tissues.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:WormBase.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:WormBase.
DR GO; GO:0008306; P:associative learning; IMP:WormBase.
DR GO; GO:0007409; P:axonogenesis; IMP:WormBase.
DR GO; GO:0040024; P:dauer larval development; IGI:WormBase.
DR GO; GO:0022401; P:negative adaptation of signaling pathway; IMP:WormBase.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0008355; P:olfactory learning; IMP:WormBase.
DR GO; GO:0061066; P:positive regulation of dauer larval development; IGI:WormBase.
DR GO; GO:1904081; P:positive regulation of transcription from RNA polymerase II promoter involved in neuron differentiation; IMP:WormBase.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:WormBase.
DR GO; GO:0030516; P:regulation of axon extension; IMP:WormBase.
DR GO; GO:1902667; P:regulation of axon guidance; IMP:WormBase.
DR GO; GO:0045664; P:regulation of neuron differentiation; IMP:WormBase.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:WormBase.
DR GO; GO:0040040; P:thermosensory behavior; IMP:WormBase.
DR GO; GO:0043052; P:thermotaxis; IMP:WormBase.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR001781; Znf_LIM.
DR Pfam; PF00046; Homeodomain; 1.
DR Pfam; PF00412; LIM; 2.
DR SMART; SM00389; HOX; 1.
DR SMART; SM00132; LIM; 2.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
DR PROSITE; PS00478; LIM_DOMAIN_1; 2.
DR PROSITE; PS50023; LIM_DOMAIN_2; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell projection; DNA-binding; Homeobox; LIM domain;
KW Metal-binding; Nucleus; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Zinc.
FT CHAIN 1..409
FT /note="LIM/homeobox protein ttx-3"
FT /id="PRO_0000428997"
FT DOMAIN 108..169
FT /note="LIM zinc-binding 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 171..232
FT /note="LIM zinc-binding 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DNA_BIND 292..351
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 245..299
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 372..409
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 245..268
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 279..293
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 1..28
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000303|PubMed:9851916"
FT /id="VSP_054579"
FT MUTAGEN 340
FT /note="F->I: In mg158; thermotaxis defects with animals
FT displaying cryophilic behavior."
FT /evidence="ECO:0000269|PubMed:11493519"
SQ SEQUENCE 409 AA; 45653 MW; 8313DB0662FFF268 CRC64;
MYFQSLSADP LDSVNTTTDF NQLAQLLLML TNSSSKETIA THVVTNSVPS AFQFDWSSHF
KEEYDLVEKL NSPQYTNLTS ISPSSSTDSN NLILRQIQIP KIEPALLNQC CLCTFAIVDK
EISVVDGKYY HNNCLRCQMC DIPFEYSDKC YVRDGVFLCR ADHAKRYQKC CRKCEIPLNR
EDMVMKAKEM IFHHACFVCF ICGIKLNPGD YYTMSPQGHL YCHAHYNAVR STVLCEEAAV
ATVPAVVAPP PPPPTTTTAP PPAAPEQPPR EASTEAEAST DEDGNGSGSQ RSKRMRTSFK
HHQLRAMKTY FALNHNPDAK DLKQLAAKTN LTKRVLQVWF QNARAKYRRE LHDGGRSSSP
LCVSAPLASM DMNPPLSSSS SGHSTDGYQL NTPPLSSEIY SPNSNYTHL
