UNC4_CAEEL
ID UNC4_CAEEL Reviewed; 252 AA.
AC P29506;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 2.
DT 03-AUG-2022, entry version 162.
DE RecName: Full=Homeobox protein unc-4;
DE AltName: Full=Homeobox protein ceh-4;
DE AltName: Full=Uncoordinated protein 4;
GN Name=unc-4; Synonyms=ceh-4; ORFNames=F26C11.2;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
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]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 37-220, AND FUNCTION.
RC STRAIN=Bristol N2;
RX PubMed=1347150; DOI=10.1038/355841a0;
RA Miller D.M. III, Shen M.M., Shamu C.E., Buerglin T.R., Ruvkun G.,
RA Dubois M.L., Ghee M., Wilson L.;
RT "C. elegans unc-4 gene encodes a homeodomain protein that determines the
RT pattern of synaptic input to specific motor neurons.";
RL Nature 355:841-845(1992).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 134-147.
RX PubMed=2571091; DOI=10.1038/341239a0;
RA Buerglin T.R., Finney M., Coulson A., Ruvkun G.;
RT "Caenorhabditis elegans has scores of homoeobox-containing genes.";
RL Nature 341:239-243(1989).
RN [4]
RP FUNCTION, INTERACTION WITH UNC-37, MUTAGENESIS OF LEU-121, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=7904971; DOI=10.1093/genetics/135.3.741;
RA Miller D.M. III, Niemeyer C.J., Chitkara P.;
RT "Dominant unc-37 mutations suppress the movement defect of a homeodomain
RT mutation in unc-4, a neural specificity gene in Caenorhabditis elegans.";
RL Genetics 135:741-753(1993).
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=7555714; DOI=10.1242/dev.121.9.2877;
RA Miller D.M. III, Niemeyer C.J.;
RT "Expression of the unc-4 homeoprotein in Caenorhabditis elegans motor
RT neurons specifies presynaptic input.";
RL Development 121:2877-2886(1995).
RN [6]
RP FUNCTION.
RX PubMed=9165118; DOI=10.1242/dev.124.9.1699;
RA Pflugrad A., Meir J.Y.-J., Barnes T.M., Miller D.M. III;
RT "The Groucho-like transcription factor UNC-37 functions with the neural
RT specificity gene unc-4 to govern motor neuron identity in C. elegans.";
RL Development 124:1699-1709(1997).
RN [7]
RP FUNCTION, INTERACTION WITH UNC-37, AND MUTAGENESIS OF PHE-174; GLY-188;
RP ARG-190 AND ARG-197.
RX PubMed=10557206; DOI=10.1101/gad.13.21.2774;
RA Winnier A.R., Meir J.Y.-J., Ross J.M., Tavernarakis N., Driscoll M.,
RA Ishihara T., Katsura I., Miller D.M. III;
RT "UNC-4/UNC-37-dependent repression of motor neuron-specific genes controls
RT synaptic choice in Caenorhabditis elegans.";
RL Genes Dev. 13:2774-2786(1999).
RN [8]
RP FUNCTION.
RX PubMed=11245684; DOI=10.1523/jneurosci.21-06-02001.2001;
RA Lickteig K.M., Duerr J.S., Frisby D.L., Hall D.H., Rand J.B.,
RA Miller D.M. III;
RT "Regulation of neurotransmitter vesicles by the homeodomain protein UNC-4
RT and its transcriptional corepressor UNC-37/groucho in Caenorhabditis
RT elegans cholinergic motor neurons.";
RL J. Neurosci. 21:2001-2014(2001).
RN [9]
RP FUNCTION.
RX PubMed=17289921; DOI=10.1101/gad.1502107;
RA Von Stetina S.E., Fox R.M., Watkins K.L., Starich T.A., Shaw J.E.,
RA Miller D.M. III;
RT "UNC-4 represses CEH-12/HB9 to specify synaptic inputs to VA motor neurons
RT in C. elegans.";
RL Genes Dev. 21:332-346(2007).
RN [10] {ECO:0000305}
RP FUNCTION.
RX PubMed=28056346; DOI=10.1016/j.neuron.2016.11.036;
RA Kerk S.Y., Kratsios P., Hart M., Mourao R., Hobert O.;
RT "Diversification of C. elegans Motor Neuron Identity via Selective Effector
RT Gene Repression.";
RL Neuron 93:80-98(2017).
CC -!- FUNCTION: Transcription factor (PubMed:1347150, PubMed:7904971,
CC PubMed:28056346). Involved in motor neuron fate determination and
CC maintenance (PubMed:28056346). In concert with unc-37, represses the
CC expression of VB-specific genes such as ceh-12, thereby preventing the
CC adoption of VB motor neuron fate (PubMed:7904971, PubMed:9165118,
CC PubMed:10557206, PubMed:11245684, PubMed:17289921). Regulates synaptic
CC specificity and the pattern of synaptic input to VA motor neurons
CC (PubMed:1347150, PubMed:7904971, PubMed:7555714). Acts as a
CC transcriptional repressor to counteract gene activation by
CC transcription factor unc-3 in a subset of motor neurons, probably by
CC binding to specific promoter elements (PubMed:28056346). Has no role in
CC axonal guidance or outgrowth (PubMed:1347150).
CC {ECO:0000269|PubMed:10557206, ECO:0000269|PubMed:11245684,
CC ECO:0000269|PubMed:1347150, ECO:0000269|PubMed:17289921,
CC ECO:0000269|PubMed:28056346, ECO:0000269|PubMed:7555714,
CC ECO:0000269|PubMed:7904971, ECO:0000269|PubMed:9165118}.
CC -!- SUBUNIT: Interacts with unc-37. {ECO:0000269|PubMed:10557206,
CC ECO:0000269|PubMed:7904971}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- TISSUE SPECIFICITY: Specifically expressed in all A-type motor neurons
CC (PubMed:7555714). The A-type motor neurons class includes 24 motor
CC neurons; 9 DA, 3 SAB motor neurons that are generated in the embryo and
CC 12 VAs arise after hatching in the first larval stage (PubMed:7555714).
CC {ECO:0000269|PubMed:7555714}.
CC -!- DEVELOPMENTAL STAGE: Most abundant during embryonic and larval
CC development. {ECO:0000269|PubMed:7555714}.
CC -!- DISRUPTION PHENOTYPE: Worms are unable to crawl backwards because VA
CC motor neurons are miswired with synaptic connections normally reserved
CC for their sister cells, the VB motor neurons.
CC {ECO:0000269|PubMed:7904971}.
CC -!- SIMILARITY: Belongs to the paired homeobox family. Unc-4 subfamily.
CC {ECO:0000305}.
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DR EMBL; Z47072; CAA87368.1; -; Genomic_DNA.
DR EMBL; X64904; CAA46108.1; -; mRNA.
DR PIR; T21388; T21388.
DR RefSeq; NP_496138.1; NM_063737.1.
DR AlphaFoldDB; P29506; -.
DR BioGRID; 39866; 1.
DR STRING; 6239.F26C11.2; -.
DR PaxDb; P29506; -.
DR EnsemblMetazoa; F26C11.2.1; F26C11.2.1; WBGene00006744.
DR GeneID; 174544; -.
DR KEGG; cel:CELE_F26C11.2; -.
DR UCSC; F26C11.2; c. elegans.
DR CTD; 32757; -.
DR WormBase; F26C11.2; CE01560; WBGene00006744; unc-4.
DR eggNOG; KOG0490; Eukaryota.
DR GeneTree; ENSGT00940000167841; -.
DR HOGENOM; CLU_084876_0_0_1; -.
DR InParanoid; P29506; -.
DR OMA; DIWNDFW; -.
DR OrthoDB; 1014909at2759; -.
DR PhylomeDB; P29506; -.
DR SignaLink; P29506; -.
DR PRO; PR:P29506; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00006744; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0030424; C:axon; IDA:WormBase.
DR GO; GO:0005634; C:nucleus; IDA:WormBase.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IMP:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0040011; P:locomotion; IMP:WormBase.
DR GO; GO:0007400; P:neuroblast fate determination; IMP:WormBase.
DR GO; GO:0050770; P:regulation of axonogenesis; IMP:WormBase.
DR GO; GO:0050803; P:regulation of synapse structure or activity; 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; IMP:UniProtKB.
DR GO; GO:0007416; P:synapse assembly; IMP:WormBase.
DR GO; GO:0008039; P:synaptic target recognition; IMP:UniProtKB.
DR GO; GO:0048489; P:synaptic vesicle transport; IMP:UniProtKB.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR Pfam; PF00046; Homeodomain; 1.
DR SMART; SM00389; HOX; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
PE 1: Evidence at protein level;
KW Developmental protein; Differentiation; DNA-binding; Homeobox;
KW Neurogenesis; Nucleus; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..252
FT /note="Homeobox protein unc-4"
FT /id="PRO_0000049347"
FT DNA_BIND 88..147
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 43..68
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 143..164
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 43..63
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 147..164
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 121
FT /note="L->F: In e2322ts; unable to crawl backwards."
FT /evidence="ECO:0000269|PubMed:7904971"
FT MUTAGEN 174
FT /note="F->E: In wdEx65; unable to crawl backwards.
FT Abolishes interaction with unc-37."
FT /evidence="ECO:0000269|PubMed:10557206"
FT MUTAGEN 188
FT /note="G->D,S: In e26/e2307; unable to crawl backwards.
FT Abolishes interaction with unc-37."
FT /evidence="ECO:0000269|PubMed:10557206"
FT MUTAGEN 190
FT /note="R->Q: In e2323; unable to crawl backwards. Abolishes
FT interaction with unc-37."
FT /evidence="ECO:0000269|PubMed:10557206"
FT MUTAGEN 197
FT /note="R->K: In e26/e2307; unable to crawl backwards.
FT Abolishes interaction with unc-37."
FT /evidence="ECO:0000269|PubMed:10557206"
SQ SEQUENCE 252 AA; 28354 MW; 89CF28B1AC69031A CRC64;
MIGALHACVD AEPKIINDIW ADFWKSQINS VLLNPSDGSE TYLASDNGKS TSSREQSTSP
DDDNLLMNED DGIALEDDND TGESAAKRRR TRTNFSGWQL EELESAFEAS HYPDVFMREA
LAMRLDLLES RVQVWFQNRR AKWRKREQNR NGSSEIKKDD GEQMETKALP TFPFSIDSIL
AVSRVPRGRR PNAKYPRVQA CKNLSPFMIP LFPITQPGGN VIREKSPPLP TQQSQIVATN
ALTTVAELLK SV
