LIM4_CAEEL
ID LIM4_CAEEL Reviewed; 355 AA.
AC G5EEA1; A0A1X7RBW0; A0A1X7RC92;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 95.
DE RecName: Full=LIM/homeobox protein lim-4 {ECO:0000305};
GN Name=lim-4 {ECO:0000312|WormBase:ZC64.4a};
GN ORFNames=ZC64.4 {ECO:0000312|WormBase:ZC64.4a};
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|EMBL:AAB17273.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM A), FUNCTION, TISSUE SPECIFICITY,
RP DEVELOPMENTAL STAGE, AND MUTAGENESIS OF ARG-243 AND 284-GLN--ASP-355.
RX PubMed=10421632; DOI=10.1101/gad.13.14.1794;
RA Sagasti A., Hobert O., Troemel E.R., Ruvkun G., Bargmann C.I.;
RT "Alternative olfactory neuron fates are specified by the LIM homeobox gene
RT lim-4.";
RL Genes Dev. 13:1794-1806(1999).
RN [2] {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 [3] {ECO:0000305}
RP FUNCTION, AND MUTAGENESIS OF 284-GLN--ASP-355.
RX PubMed=14568548; DOI=10.1016/s0012-1606(03)00447-0;
RA Tsalik E.L., Niacaris T., Wenick A.S., Pau K., Avery L., Hobert O.;
RT "LIM homeobox gene-dependent expression of biogenic amine receptors in
RT restricted regions of the C. elegans nervous system.";
RL Dev. Biol. 263:81-102(2003).
RN [4] {ECO:0000305}
RP FUNCTION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF 284-GLN--ASP-355.
RX PubMed=16168406; DOI=10.1016/j.ydbio.2005.08.013;
RA Zheng X., Chung S., Tanabe T., Sze J.Y.;
RT "Cell-type specific regulation of serotonergic identity by the C. elegans
RT LIM-homeodomain factor LIM-4.";
RL Dev. Biol. 286:618-628(2005).
RN [5] {ECO:0000305}
RP FUNCTION, AND INTERACTION WITH SOX-2.
RX PubMed=26341465; DOI=10.15252/embj.201592188;
RA Alqadah A., Hsieh Y.W., Vidal B., Chang C., Hobert O., Chuang C.F.;
RT "Postmitotic diversification of olfactory neuron types is mediated by
RT differential activities of the HMG-box transcription factor SOX-2.";
RL EMBO J. 34:2574-2589(2015).
RN [6] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF
RP 284-GLN--ASP-355.
RX PubMed=26305787; DOI=10.1371/journal.pgen.1005480;
RA Kim J., Yeon J., Choi S.K., Huh Y.H., Fang Z., Park S.J., Kim M.O.,
RA Ryoo Z.Y., Kang K., Kweon H.S., Jeon W.B., Li C., Kim K.;
RT "The Evolutionarily Conserved LIM Homeodomain Protein LIM-4/LHX6 Specifies
RT the Terminal Identity of a Cholinergic and Peptidergic C. elegans
RT Sensory/Inter/Motor Neuron-Type.";
RL PLoS Genet. 11:e1005480-e1005480(2015).
CC -!- FUNCTION: Transcription factor that binds to the promoter of target
CC genes (PubMed:26305787, PubMed:16168406, PubMed:26341465). Regulates
CC genes involved in serotonin synthesis and release in serotonergic ADF
CC neurons (PubMed:26305787, PubMed:16168406). Involved in specification
CC of neuron cell fate, olfactory receptor expression, locomotion, and
CC foraging behavior (PubMed:10421632, PubMed:26305787). Required in AWB
CC olfactory neurons to repress AWC cell fate and promote the AWB cell
CC fate during early development (PubMed:10421632). Cooperates with
CC additional factors to direct the differentiation of the olfactory
CC neurons, functioning with the transcription factor sox-2 to suppress
CC AWC terminal differentiation and promote AWB neuron differentiation
CC (PubMed:26341465). Involved in regulating terminal specification and
CC maintenance of the SMB sensory/inter/motor neurons (PubMed:26305787).
CC Plays a role in regulation of RID motor neuron differentiation, but is
CC dispensable for motor axon outgrowth in the dorsal nerve cord
CC (PubMed:14568548). May regulate its own expression (PubMed:10421632,
CC PubMed:26305787). {ECO:0000269|PubMed:10421632,
CC ECO:0000269|PubMed:14568548, ECO:0000269|PubMed:16168406,
CC ECO:0000269|PubMed:26305787, ECO:0000269|PubMed:26341465}.
CC -!- SUBUNIT: Interacts with transcription factor sox-2.
CC {ECO:0000269|PubMed:26341465}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00108,
CC ECO:0000255|RuleBase:RU000682}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=a {ECO:0000312|WormBase:ZC64.4a};
CC IsoId=G5EEA1-1; Sequence=Displayed;
CC Name=b {ECO:0000312|WormBase:ZC64.4b};
CC IsoId=G5EEA1-2; Sequence=VSP_061067;
CC Name=c {ECO:0000312|WormBase:ZC64.4c};
CC IsoId=G5EEA1-3; Sequence=VSP_061066;
CC -!- TISSUE SPECIFICITY: Expressed in the AWB sensory neurons and in one RME
CC motor neuron (RMEV), two RMD motor neurons (RMDL and RMDR), the RID,
CC RIV, SAA and SIA interneurons and the SMB sensory/inter/motor neurons.
CC {ECO:0000269|PubMed:10421632, ECO:0000269|PubMed:26305787}.
CC -!- DEVELOPMENTAL STAGE: Expressed in larvae and adults in neurons in the
CC anterior ganglia (PubMed:10421632). Expressed in the precursor of
CC serotonergic ADF neurons (PubMed:16168406). Expressed in the SMB
CC sensory/inter/motor neurons at larval stage L1 (PubMed:26305787).
CC {ECO:0000269|PubMed:10421632, ECO:0000269|PubMed:16168406,
CC ECO:0000269|PubMed:26305787}.
CC -!- CAUTION: It has been reported that lim-4 is expressed in the SIA
CC interneurons (PubMed:10421632). However, a subsequent report suggests
CC that this was a mis-identification, instead indicating that the correct
CC cell type is the SMB sensory/inter/motor neuron (PubMed:26305787).
CC {ECO:0000269|PubMed:10421632, ECO:0000269|PubMed:26305787}.
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DR EMBL; U72348; AAB17273.1; -; mRNA.
DR EMBL; BX284606; CCD71434.1; -; Genomic_DNA.
DR EMBL; BX284606; SMQ44709.1; -; Genomic_DNA.
DR EMBL; BX284606; SMQ44710.1; -; Genomic_DNA.
DR PIR; T27637; T27637.
DR RefSeq; NP_508669.1; NM_076268.1. [G5EEA1-1]
DR AlphaFoldDB; G5EEA1; -.
DR SMR; G5EEA1; -.
DR IntAct; G5EEA1; 2.
DR STRING; 6239.ZC64.4; -.
DR EPD; G5EEA1; -.
DR PaxDb; G5EEA1; -.
DR EnsemblMetazoa; ZC64.4a.1; ZC64.4a.1; WBGene00002987. [G5EEA1-1]
DR EnsemblMetazoa; ZC64.4b.1; ZC64.4b.1; WBGene00002987. [G5EEA1-2]
DR EnsemblMetazoa; ZC64.4c.1; ZC64.4c.1; WBGene00002987. [G5EEA1-3]
DR GeneID; 180672; -.
DR CTD; 180672; -.
DR WormBase; ZC64.4a; CE25675; WBGene00002987; lim-4.
DR WormBase; ZC64.4b; CE51976; WBGene00002987; lim-4.
DR WormBase; ZC64.4c; CE52031; WBGene00002987; lim-4.
DR eggNOG; KOG0490; Eukaryota.
DR GeneTree; ENSGT00940000172226; -.
DR HOGENOM; CLU_781277_0_0_1; -.
DR InParanoid; G5EEA1; -.
DR OMA; RQKKWHQ; -.
DR OrthoDB; 948890at2759; -.
DR PhylomeDB; G5EEA1; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00002987; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR ExpressionAtlas; G5EEA1; baseline and differential.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISS:WormBase.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IMP:UniProtKB.
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:0001708; P:cell fate specification; IMP:WormBase.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0045664; P:regulation of neuron differentiation; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:WormBase.
DR GO; GO:0042427; P:serotonin biosynthetic process; IMP:UniProtKB.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
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; PS50071; HOMEOBOX_2; 1.
DR PROSITE; PS00478; LIM_DOMAIN_1; 1.
DR PROSITE; PS50023; LIM_DOMAIN_2; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; DNA-binding; Homeobox; LIM domain; Metal-binding;
KW Nucleus; Reference proteome; Repeat; Transcription;
KW Transcription regulation; Zinc.
FT CHAIN 1..355
FT /note="LIM/homeobox protein lim-4"
FT /id="PRO_0000452844"
FT DOMAIN 96..155
FT /note="LIM zinc-binding 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 166..228
FT /note="LIM zinc-binding 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DNA_BIND 239..298
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 291..336
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 306..336
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 152..162
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000305"
FT /id="VSP_061066"
FT VAR_SEQ 152..160
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_061067"
FT MUTAGEN 243
FT /note="R->Q: In ky395; Abnormal expression of olfactory
FT receptor str-2 in AWB olfactory neurons, defects in
FT foraging behavior, and aberrant movements. Repulsive
FT olfactory neuron AWB is transformed into the attractive
FT olfactory neuron AWC."
FT /evidence="ECO:0000269|PubMed:10421632"
FT MUTAGEN 284..355
FT /note="Missing: In ky403; Abnormal expression of olfactory
FT receptor str-2 in AWB olfactory neurons, defects in
FT foraging behavior, and aberrant movements. Repulsive
FT olfactory neuron AWB is transformed into the attractive
FT olfactory neuron AWC. Reduced expression of tph-1 and
FT reduced serotonin immunoreactivity in serotonergic ADF
FT neurons. Expression of neuropeptide flp-12 is abolished in
FT the SMB sensory/inter/motor neurons. Expression of
FT terminally differentiated SMB markers including cholinergic
FT genes is abolished, but pan-neuronal genes such as
FT chaperone unc-119 are unchanged. Exhibits aberrant
FT expression of some but not all genes which are markers of
FT RID motorneuron differentiation."
FT /evidence="ECO:0000269|PubMed:10421632,
FT ECO:0000269|PubMed:14568548, ECO:0000269|PubMed:16168406,
FT ECO:0000269|PubMed:26305787"
SQ SEQUENCE 355 AA; 39567 MW; 854A1EC1CAE8E117 CRC64;
MDAHLVQAKK TSTASELSDS SLTFPFIGDY LSSPSLTTSD YVSDCSNLTV EGPVPANQEF
SSSDESSVYI SSALRLADYA FTPDDNIRIK PDAVIVICTQ CQHQIQDKFF LSIDGRNYHE
NCLQCSTCEN PLSNKCFYKD KTFYCKGCYF RTHVTSTASS CRELGPKCAS CDRTIQATDW
VRRARNYVYH LACFSCNQCK RQLSTGEEYA LQEGNLLCKQ HFLELVEGDS GVSSQKAKTK
RVRTTFAEDQ LSVLQTYFNR DSNPDGADLE KIASMTGLSK RVTQVWFQNS RARQKKWHQK
SEGDNGDSQR SSVGPSSPSQ KSDSSSEMMY PTSVTTSVED AIPDSIVILG SLQFD
