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LIM/homeobox protein ttx-3 (Abnormal thermotaxis protein 3)

 TTX3_CAEEL              Reviewed;         409 AA.
G5EE86; B6VQ91;
14-MAY-2014, integrated into UniProtKB/Swiss-Prot.
14-DEC-2011, sequence version 1.
27-SEP-2017, entry version 47.
RecName: Full=LIM/homeobox protein ttx-3 {ECO:0000303|PubMed:9292724};
AltName: Full=Abnormal thermotaxis protein 3;
Name=ttx-3 {ECO:0000312|EMBL:CAB03956.3,
ECO:0000312|WormBase:C40H5.5a}; ORFNames=C40H5.5;
Caenorhabditis elegans.
Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
Rhabditoidea; Rhabditidae; Peloderinae; Caenorhabditis.
NCBI_TaxID=6239;
[1] {ECO:0000305, ECO:0000312|EMBL:AAB97099.1}
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, SUBCELLULAR
LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
PHENOTYPE.
STRAIN=Bristol N2 {ECO:0000312|EMBL:AAB97099.1};
PubMed=9292724; DOI=10.1016/S0896-6273(00)80944-7;
Hobert O., Mori I., Yamashita Y., Honda H., Ohshima Y., Liu Y.,
Ruvkun G.;
"Regulation of interneuron function in the C. elegans thermoregulatory
pathway by the ttx-3 LIM homeobox gene.";
Neuron 19:345-357(1997).
[2] {ECO:0000312|EMBL:CAB03956.3}
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=Bristol N2 {ECO:0000312|EMBL:CAB03956.3};
PubMed=9851916; DOI=10.1126/science.282.5396.2012;
The C. elegans sequencing consortium;
"Genome sequence of the nematode C. elegans: a platform for
investigating biology.";
Science 282:2012-2018(1998).
[3] {ECO:0000305}
FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL
STAGE, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF PHE-340.
PubMed=11493519;
Altun-Gultekin Z., Andachi Y., Tsalik E.L., Pilgrim D., Kohara Y.,
Hobert O.;
"A regulatory cascade of three homeobox genes, ceh-10, ttx-3 and ceh-
23, controls cell fate specification of a defined interneuron class in
C. elegans.";
Development 128:1951-1969(2001).
[4] {ECO:0000305}
FUNCTION, AND DISRUPTION PHENOTYPE.
PubMed=16051801; DOI=10.1126/science.1114209;
Remy J.J., Hobert O.;
"An interneuronal chemoreceptor required for olfactory imprinting in
C. elegans.";
Science 309:787-790(2005).
[5] {ECO:0000305}
FUNCTION, AND DISRUPTION PHENOTYPE.
STRAIN=Bristol N2 {ECO:0000269|PubMed:21055415};
PubMed=21055415; DOI=10.1016/j.mad.2010.10.005;
Shen L., Hu Y., Cai T., Lin X., Wang D.;
"Regulation of longevity by genes required for the functions of AIY
interneuron in nematode Caenorhabditis elegans.";
Mech. Ageing Dev. 131:732-738(2010).
[6] {ECO:0000305}
FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND DISRUPTION
PHENOTYPE.
PubMed=24353061; DOI=10.1242/dev.099721;
Zhang F., Bhattacharya A., Nelson J.C., Abe N., Gordon P.,
Lloret-Fernandez C., Maicas M., Flames N., Mann R.S.,
Colon-Ramos D.A., Hobert O.;
"The LIM and POU homeobox genes ttx-3 and unc-86 act as terminal
selectors in distinct cholinergic and serotonergic neuron types.";
Development 141:422-435(2014).
-!- FUNCTION: Required for specification of the AIA and AIY
interneurons and the NSM neurons. Positively regulates the
expression of a number of genes including ceh-23, kal-1, hen-1,
ser-2, unc-17 and sra-11 in AIY interneurons and cat-4, flp-4,
bas-1, ptps-1 and mgl-1 in NSM neurons. Also acts in an
autoregulatory feedback loop to maintain its own expression. Plays
a role in the thermotactic response, olfactory imprinting,
regulation of longevity, control of dauer formation and axon
outgrowth and pathfinding. Not required for normal chemosensory
behavior. {ECO:0000269|PubMed:11493519,
ECO:0000269|PubMed:16051801, ECO:0000269|PubMed:21055415,
ECO:0000269|PubMed:24353061, ECO:0000269|PubMed:9292724}.
-!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-
ProRule:PRU00108, ECO:0000269|PubMed:11493519,
ECO:0000269|PubMed:9292724}. Perikaryon
{ECO:0000269|PubMed:11493519, ECO:0000269|PubMed:9292724}. Cell
projection, axon {ECO:0000269|PubMed:11493519,
ECO:0000269|PubMed:9292724}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=a {ECO:0000269|PubMed:9292724, ECO:0000269|PubMed:9851916};
IsoId=G5EE86-1; Sequence=Displayed;
Name=b {ECO:0000269|PubMed:9851916};
IsoId=G5EE86-2; Sequence=VSP_054579;
Note=No experimental confirmation available. {ECO:0000305};
-!- TISSUE SPECIFICITY: Expressed in the AIA, AIN and AIY
interneurons, and in the NSM neurons. Expressed also in ADL and
ASI sensory neurons in 60-70% of L2 larvae. Expression is also
detected in head muscles of embryos and some early larvae but not
late larvae or adults. {ECO:0000269|PubMed:11493519,
ECO:0000269|PubMed:24353061, ECO:0000269|PubMed:9292724}.
-!- DEVELOPMENTAL STAGE: Expressed during embryogenesis and persists
through to adulthood in AIY interneurons. Expressed at L1 stage
and through adulthood in AIA and NSM neurons. Expression is
detected in head muscles of all 1.5 and 2-fold embryos, 47% of
embryos just before hatching and 6% of early larvae with no
expression in head muscles of late stage larvae or adults.
{ECO:0000269|PubMed:11493519, ECO:0000269|PubMed:24353061,
ECO:0000269|PubMed:9292724}.
-!- DISRUPTION PHENOTYPE: Animals are cryophilic and move toward lower
temperatures irrespective of cultivation temperature in contrast
to wild-type animals which move toward their cultivation
temperature when placed on a temperature gradient. AIA and AIY
interneurons display defective neurite morphology. NSM neurons
display loss of or reduced expression of a number of terminal
identity markers including cat-4, flp-4, bas-1, ptps-1 and mgl-1.
Reduced expression of ceh-23, kal-1, C36B7.7, ser-2, unc-17 and
sra-11 is observed in AIY interneurons. Preexposure to odorants
fails to leave an olfactory imprint. Mean lifespan is reduced by
10% with decreased pharyngeal pumping and increased intestinal
autofluorescence caused by lysosomal deposits of lipofuscin,
indicative of cellular damage and aging. Formation of very few
dauers in starvation conditions. No defects observed in brood
size, egg number or chemotactic behavior toward volatile
chemicals. {ECO:0000269|PubMed:11493519,
ECO:0000269|PubMed:16051801, ECO:0000269|PubMed:21055415,
ECO:0000269|PubMed:24353061, ECO:0000269|PubMed:9292724}.
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EMBL; U72211; AAB97099.1; -; mRNA.
EMBL; Z81482; CAB03956.3; -; Genomic_DNA.
EMBL; Z81482; CAR97817.1; -; Genomic_DNA.
PIR; T19871; T19871.
RefSeq; NP_001257168.1; NM_001270239.1. [G5EE86-1]
RefSeq; NP_001257169.1; NM_001270240.1. [G5EE86-2]
UniGene; Cel.19674; -.
ProteinModelPortal; G5EE86; -.
SMR; G5EE86; -.
BioGrid; 46265; 1.
STRING; 6239.C40H5.5a; -.
PaxDb; G5EE86; -.
EnsemblMetazoa; C40H5.5a; C40H5.5a; WBGene00006654. [G5EE86-1]
GeneID; 181357; -.
KEGG; cel:CELE_C40H5.5; -.
CTD; 181357; -.
WormBase; C40H5.5a; CE27107; WBGene00006654; ttx-3. [G5EE86-1]
WormBase; C40H5.5b; CE43132; WBGene00006654; ttx-3. [G5EE86-2]
eggNOG; KOG0490; Eukaryota.
eggNOG; ENOG410YIJ3; LUCA.
GeneTree; ENSGT00760000118921; -.
HOGENOM; HOG000015956; -.
InParanoid; G5EE86; -.
KO; K09373; -.
OMA; HGISGDH; -.
OrthoDB; EOG091G13BH; -.
PhylomeDB; G5EE86; -.
PRO; PR:G5EE86; -.
Proteomes; UP000001940; Chromosome X.
Bgee; WBGene00006654; -.
GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
GO; GO:0005634; C:nucleus; ISS:WormBase.
GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO; GO:0000977; F:RNA polymerase II regulatory region sequence-specific DNA binding; IDA:WormBase.
GO; GO:0008306; P:associative learning; IMP:WormBase.
GO; GO:0007409; P:axonogenesis; IMP:WormBase.
GO; GO:0040024; P:dauer larval development; IGI:WormBase.
GO; GO:0022401; P:negative adaptation of signaling pathway; IMP:WormBase.
GO; GO:0008355; P:olfactory learning; IMP:WormBase.
GO; GO:0061066; P:positive regulation of dauer larval development; IGI:WormBase.
GO; GO:1904081; P:positive regulation of transcription from RNA polymerase II promoter involved in neuron differentiation; IMP:WormBase.
GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:WormBase.
GO; GO:0030516; P:regulation of axon extension; IMP:WormBase.
GO; GO:1902667; P:regulation of axon guidance; IMP:WormBase.
GO; GO:0045664; P:regulation of neuron differentiation; IMP:WormBase.
GO; GO:0006355; P:regulation of transcription, DNA-templated; ISS:WormBase.
GO; GO:0040040; P:thermosensory behavior; IMP:WormBase.
GO; GO:0043052; P:thermotaxis; IMP:WormBase.
GO; GO:0006351; P:transcription, DNA-templated; IEA:UniProtKB-KW.
CDD; cd00086; homeodomain; 1.
InterPro; IPR009057; Homeobox-like.
InterPro; IPR017970; Homeobox_CS.
InterPro; IPR001356; Homeobox_dom.
InterPro; IPR001781; Znf_LIM.
Pfam; PF00046; Homeobox; 1.
Pfam; PF00412; LIM; 2.
SMART; SM00389; HOX; 1.
SMART; SM00132; LIM; 2.
SUPFAM; SSF46689; SSF46689; 1.
PROSITE; PS00027; HOMEOBOX_1; 1.
PROSITE; PS50071; HOMEOBOX_2; 1.
PROSITE; PS00478; LIM_DOMAIN_1; 2.
PROSITE; PS50023; LIM_DOMAIN_2; 2.
1: Evidence at protein level;
Alternative splicing; Cell projection; Complete proteome; DNA-binding;
Homeobox; LIM domain; Metal-binding; Nucleus; Reference proteome;
Repeat; Transcription; Transcription regulation; Zinc.
CHAIN 1 409 LIM/homeobox protein ttx-3.
/FTId=PRO_0000428997.
DOMAIN 108 169 LIM zinc-binding 1. {ECO:0000255|PROSITE-
ProRule:PRU00125}.
DOMAIN 171 232 LIM zinc-binding 2. {ECO:0000255|PROSITE-
ProRule:PRU00125}.
DNA_BIND 292 351 Homeobox. {ECO:0000255|PROSITE-
ProRule:PRU00108}.
VAR_SEQ 1 28 Missing (in isoform b).
{ECO:0000303|PubMed:9851916}.
/FTId=VSP_054579.
MUTAGEN 340 340 F->I: In mg158; thermotaxis defects with
animals displaying cryophilic behavior.
{ECO:0000269|PubMed:11493519}.
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


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