RUNX1_CAEEL
ID RUNX1_CAEEL Reviewed; 301 AA.
AC G5EFQ5;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 95.
DE RecName: Full=Runt-related transcription factor rnt-1 {ECO:0000305};
GN Name=rnt-1 {ECO:0000312|WormBase:B0414.2};
GN Synonyms=mab-2 {ECO:0000312|WormBase:B0414.2},
GN run-1 {ECO:0000312|EMBL:AAD54940.1, ECO:0000312|WormBase:B0414.2};
GN ORFNames=B0414.2 {ECO:0000312|WormBase:B0414.2};
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:AAD54940.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=10675037; DOI=10.1016/s0378-1119(99)00488-6;
RA Bae S.-C., Lee J.;
RT "cDNA cloning of run, a Caenorhabditis elegans Runt domain encoding gene.";
RL Gene 241:255-258(2000).
RN [2] {ECO:0000312|EMBL:BAA77765.1}
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Kagoshima H., Burglin T.R.;
RT "cDNA of a Homolog for Drosophila runt from C. elegans.";
RL Submitted (MAY-1999) to the EMBL/GenBank/DDBJ databases.
RN [3] {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 [4] {ECO:0000305}
RP FUNCTION, INTERACTION WITH SMA-4, AND DEVELOPMENTAL STAGE.
RX PubMed=15385167; DOI=10.1016/j.ydbio.2004.07.029;
RA Ji Y.J., Nam S., Jin Y.H., Cha E.J., Lee K.S., Choi K.Y., Song H.O.,
RA Lee J., Bae S.C., Ahnn J.;
RT "RNT-1, the C. elegans homologue of mammalian RUNX transcription factors,
RT regulates body size and male tail development.";
RL Dev. Biol. 274:402-412(2004).
RN [5] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF 39-TRP--PHE-301 AND ILE-112.
RX PubMed=16236764; DOI=10.1242/dev.02102;
RA Nimmo R., Antebi A., Woollard A.;
RT "mab-2 encodes RNT-1, a C. elegans Runx homologue essential for controlling
RT cell proliferation in a stem cell-like developmental lineage.";
RL Development 132:5043-5054(2005).
RN [6] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, AND DEVELOPMENTAL STAGE.
RX PubMed=16226243; DOI=10.1016/j.ydbio.2005.08.034;
RA Kagoshima H., Sawa H., Mitani S., Burglin T.R., Shigesada K., Kohara Y.;
RT "The C. elegans RUNX transcription factor RNT-1/MAB-2 is required for
RT asymmetrical cell division of the T blast cell.";
RL Dev. Biol. 287:262-273(2005).
RN [7] {ECO:0000305}
RP FUNCTION, INTERACTION WITH BRO-1, AND MUTAGENESIS OF ILE-112.
RX PubMed=17933794; DOI=10.1242/dev.008276;
RA Kagoshima H., Nimmo R., Saad N., Tanaka J., Miwa Y., Mitani S., Kohara Y.,
RA Woollard A.;
RT "The C. elegans CBFbeta homologue BRO-1 interacts with the Runx factor,
RT RNT-1, to promote stem cell proliferation and self-renewal.";
RL Development 134:3905-3915(2007).
RN [8] {ECO:0000305}
RP FUNCTION.
RX PubMed=18158917; DOI=10.1016/j.bbrc.2007.12.097;
RA Shim J., Lee J.;
RT "Regulation of rnt-1 expression mediated by the opposing effects of BRO-1
RT and DBL-1 in the nematode Caenorhabditis elegans.";
RL Biochem. Biophys. Res. Commun. 367:130-136(2008).
RN [9] {ECO:0000305}
RP FUNCTION, TISSUE SPECIFICITY, PHOSPHORYLATION AT SER-255, UBIQUITINATION,
RP AND MUTAGENESIS OF SER-255.
RX PubMed=22308034; DOI=10.1074/jbc.m111.314146;
RA Lee K., Shim J., Bae J., Kim Y.J., Lee J.;
RT "Stabilization of RNT-1 protein, runt-related transcription factor (RUNX)
RT protein homolog of Caenorhabditis elegans, by oxidative stress through
RT mitogen-activated protein kinase pathway.";
RL J. Biol. Chem. 287:10444-10452(2012).
RN [10] {ECO:0000305}
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=31740621; DOI=10.1242/dev.180034;
RA van der Horst S.E.M., Cravo J., Woollard A., Teapal J., van den Heuvel S.;
RT "C. elegans Runx/CBFbeta suppresses POP-1 TCF to convert asymmetric to
RT proliferative division of stem cell-like seam cells.";
RL Development 146:0-0(2019).
RN [11] {ECO:0000305}
RP FUNCTION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF 104-ARG--PHE-301.
RX PubMed=31083672; DOI=10.1371/journal.pone.0216417;
RA Robinson S.B., Refai O., Hardaway J.A., Sturgeon S., Popay T.,
RA Bermingham D.P., Freeman P., Wright J., Blakely R.D.;
RT "Dopamine-dependent, swimming-induced paralysis arises as a consequence of
RT loss of function mutations in the RUNX transcription factor RNT-1.";
RL PLoS ONE 14:e0216417-e0216417(2019).
CC -!- FUNCTION: Transcription factor (By similarity). Binds to regulatory DNA
CC sequences in order to modulate transcription; negatively autoregulates
CC its own expression, perhaps dependent upon CBF beta homolog bro-1
CC (PubMed:18158917). Promotes proliferation, and prevents
CC differentiation, of seam cells, a stem cell-like lineage, acting in
CC concert with bro-1 (PubMed:31740621). Required for controlling cell
CC proliferation in the seam cells, perhaps by repressing expression of
CC cyclin-dependent kinase inhibitor cki-1 (PubMed:16236764,
CC PubMed:17933794). Inhibition of seam cell differentiation is regulated
CC by rnt-1 and bro-1, perhaps acting upstream of pop-1, by antagonizing
CC pop-1 repressor function (PubMed:31740621). Required for asymmetrical
CC cell divisions in the lineage derived from a posterior embryonic seam
CC cell, the T blast cell, and for asymmetric expression of zinc finger
CC protein tlp-1 (PubMed:16226243). Regulates growth and male tail
CC development (PubMed:15385167, PubMed:16236764, PubMed:16226243,
CC PubMed:31083672). Involved in the oxidative stress response, perhaps
CC downstream of the p38 MAP kinase pathway, and acting as part of a
CC negative feedback loop via a transcriptional target gene, tyrosine-
CC protein phosphatase vhp-1 (PubMed:22308034). Positively modulates
CC dopaminergic signaling in a non-cell autonomous manner
CC (PubMed:31083672). May be involved in TGF-beta signaling
CC (PubMed:15385167). {ECO:0000250|UniProtKB:Q13950,
CC ECO:0000269|PubMed:15385167, ECO:0000269|PubMed:16226243,
CC ECO:0000269|PubMed:16236764, ECO:0000269|PubMed:17933794,
CC ECO:0000269|PubMed:18158917, ECO:0000269|PubMed:22308034,
CC ECO:0000269|PubMed:31083672, ECO:0000269|PubMed:31740621}.
CC -!- SUBUNIT: Interacts with CBFbeta homolog bro-1; acts to increase the
CC affinity and specificity of interaction of rnt-1 with DNA
CC (PubMed:17933794). Interacts with TGF-beta pathway protein sma-4
CC (PubMed:15385167). {ECO:0000269|PubMed:15385167,
CC ECO:0000269|PubMed:17933794}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00399,
CC ECO:0000269|PubMed:16226243, ECO:0000269|PubMed:16236764,
CC ECO:0000269|PubMed:31740621}. Note=High level of nuclear localization
CC in interphase seam cells before the symmetric larval stage L2
CC divisions, but subsequently rnt-1 disappears during mitosis, and
CC largely remains absent when the nuclei reform in telophase.
CC {ECO:0000269|PubMed:31740621}.
CC -!- TISSUE SPECIFICITY: Expressed in the intestine.
CC {ECO:0000269|PubMed:22308034}.
CC -!- DEVELOPMENTAL STAGE: Expressed in seam cells in embryos from around 260
CC minutes post fertilization and in all subsequent developmental stages
CC (PubMed:16236764, PubMed:16226243). Also expressed at the comma stage,
CC at about 400 min, in the body wall muscle cells (PubMed:16226243).
CC Expressed in males, in the descendant cells of the V5, V6, and T
CC lineages, which include all the A-type neuron, the B-type neuron, and
CC the structural cells of the male-specific sense organs, known as rays,
CC from the mid-L3 larval stage to L4 stage (PubMed:15385167). Expressed
CC in dopaminergic neurons at larval stage L4 (PubMed:31083672).
CC {ECO:0000269|PubMed:15385167, ECO:0000269|PubMed:16226243,
CC ECO:0000269|PubMed:16236764, ECO:0000269|PubMed:31083672}.
CC -!- PTM: May be ubiquitinated in order to be targeted for proteasome-
CC mediated degradation in intestinal cells.
CC {ECO:0000269|PubMed:22308034}.
CC -!- PTM: May be phosphorylated by members of the p38 MAP kinase pathway.
CC {ECO:0000269|PubMed:22308034}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes embryonic
CC lethality and missing male-specific sense organs, known as rays
CC (PubMed:16236764). In hermaphrodites, RNAi-mediated knockdown causes a
CC slight (5%) reduction in body length at adulthood (PubMed:16236764).
CC {ECO:0000269|PubMed:16236764}.
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DR EMBL; AF153275; AAD54940.1; -; mRNA.
DR EMBL; AB027412; BAA77765.1; -; mRNA.
DR EMBL; BX284601; CCD61898.1; -; Genomic_DNA.
DR PIR; T15229; T15229.
DR PIR; T37326; T37326.
DR RefSeq; NP_491679.1; NM_059278.5.
DR AlphaFoldDB; G5EFQ5; -.
DR SMR; G5EFQ5; -.
DR ELM; G5EFQ5; -.
DR IntAct; G5EFQ5; 2.
DR STRING; 6239.B0414.2; -.
DR PaxDb; G5EFQ5; -.
DR EnsemblMetazoa; B0414.2.1; B0414.2.1; WBGene00004393.
DR EnsemblMetazoa; B0414.2.2; B0414.2.2; WBGene00004393.
DR EnsemblMetazoa; B0414.2.3; B0414.2.3; WBGene00004393.
DR GeneID; 172243; -.
DR CTD; 172243; -.
DR WormBase; B0414.2; CE24772; WBGene00004393; rnt-1.
DR eggNOG; KOG3982; Eukaryota.
DR GeneTree; ENSGT00940000170974; -.
DR HOGENOM; CLU_944104_0_0_1; -.
DR InParanoid; G5EFQ5; -.
DR OMA; MIPPPWW; -.
DR OrthoDB; 1261570at2759; -.
DR Reactome; R-CEL-549127; Organic cation transport.
DR Reactome; R-CEL-8877330; RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs).
DR Reactome; R-CEL-8878166; Transcriptional regulation by RUNX2.
DR Reactome; R-CEL-8934593; Regulation of RUNX1 Expression and Activity.
DR Reactome; R-CEL-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
DR Reactome; R-CEL-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs.
DR Reactome; R-CEL-8939243; RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known.
DR Reactome; R-CEL-8939245; RUNX1 regulates transcription of genes involved in BCR signaling.
DR Reactome; R-CEL-8939246; RUNX1 regulates transcription of genes involved in differentiation of myeloid cells.
DR Reactome; R-CEL-8939247; RUNX1 regulates transcription of genes involved in interleukin signaling.
DR Reactome; R-CEL-8939902; Regulation of RUNX2 expression and activity.
DR Reactome; R-CEL-8941326; RUNX2 regulates bone development.
DR Reactome; R-CEL-8941855; RUNX3 regulates CDKN1A transcription.
DR Reactome; R-CEL-8941858; Regulation of RUNX3 expression and activity.
DR Reactome; R-CEL-8951430; RUNX3 regulates WNT signaling.
DR Reactome; R-CEL-8951671; RUNX3 regulates YAP1-mediated transcription.
DR Reactome; R-CEL-8951936; RUNX3 regulates p14-ARF.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00004393; Expressed in intestine and 4 other tissues.
DR GO; GO:0016513; C:core-binding factor complex; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IMP:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IMP:UniProtKB.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IMP:UniProtKB.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:UniProtKB.
DR GO; GO:0046332; F:SMAD binding; IPI:WormBase.
DR GO; GO:0008356; P:asymmetric cell division; IMP:UniProtKB.
DR GO; GO:0098722; P:asymmetric stem cell division; IGI:UniProtKB.
DR GO; GO:0042417; P:dopamine metabolic process; IMP:UniProtKB.
DR GO; GO:0009792; P:embryo development ending in birth or egg hatching; IMP:WormBase.
DR GO; GO:0010629; P:negative regulation of gene expression; IGI:UniProtKB.
DR GO; GO:2000737; P:negative regulation of stem cell differentiation; IGI:UniProtKB.
DR GO; GO:0045138; P:nematode male tail tip morphogenesis; IMP:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IMP:WormBase.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0090326; P:positive regulation of locomotion involved in locomotory behavior; IMP:UniProtKB.
DR GO; GO:2000648; P:positive regulation of stem cell proliferation; IGI:UniProtKB.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:UniProtKB.
DR GO; GO:0006970; P:response to osmotic stress; IMP:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; IMP:UniProtKB.
DR Gene3D; 2.60.40.720; -; 1.
DR InterPro; IPR000040; AML1_Runt.
DR InterPro; IPR008967; p53-like_TF_DNA-bd.
DR InterPro; IPR012346; p53/RUNT-type_TF_DNA-bd_sf.
DR InterPro; IPR013524; Runt_dom.
DR PANTHER; PTHR11950; PTHR11950; 1.
DR Pfam; PF00853; Runt; 1.
DR PRINTS; PR00967; ONCOGENEAML1.
DR SUPFAM; SSF49417; SSF49417; 1.
DR PROSITE; PS51062; RUNT; 1.
PE 1: Evidence at protein level;
KW Developmental protein; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..301
FT /note="Runt-related transcription factor rnt-1"
FT /id="PRO_0000453625"
FT DOMAIN 10..138
FT /note="Runt"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00399"
FT REGION 40..44
FT /note="Interaction with DNA"
FT REGION 95..103
FT /note="Interaction with DNA"
FT REGION 128..137
FT /note="Interaction with DNA"
FT REGION 237..301
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 256..274
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 283..301
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 99
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00399"
FT BINDING 130
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00399"
FT MOD_RES 255
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:22308034"
FT MUTAGEN 39..301
FT /note="Missing: In os58; embryonic lethality."
FT /evidence="ECO:0000269|PubMed:16236764"
FT MUTAGEN 104..301
FT /note="Missing: In vt34; significant (~20%) reduction in
FT body length at adulthood. Males are unable to produce
FT successful matings, as a result of abnormal tail
FT morphology. Causes robust dopamine-dependent swimming-
FT induced paralysis, as a result of changes in the expression
FT or activity of the dopamine transporter dat-1. Hundred-fold
FT reduction in dat-1 mRNA levels at larval stage L4.
FT Paralysis occurs sooner on a dat-1 mutant background."
FT /evidence="ECO:0000269|PubMed:31083672"
FT MUTAGEN 112
FT /note="I->K: In e1241; absent male-specific sense organs,
FT known as rays. Affects heterodimer formation with bro-1 and
FT therefore high affinity DNA binding."
FT /evidence="ECO:0000269|PubMed:16236764,
FT ECO:0000269|PubMed:17933794"
FT MUTAGEN 255
FT /note="S->A: Dramatically decreases the level of
FT phosphorylation."
FT /evidence="ECO:0000269|PubMed:22308034"
SQ SEQUENCE 301 AA; 33932 MW; CA0F1AC07469D03D CRC64;
MTNVFHHVRN FIEQQPAPAK TLEKSSSPNI LYTALPKHWR SNKSFQEPFY VVLLTPVPDN
TEVSIWAGND EKPCEEVRNE KAKVHRQVAK FNDLRFVGRS GRGRKFHLTI VIHSAPMMVA
TVKNVIKVTV DGPRDARIPK PQGSLKRQAE QQTIFPNDII RTPGPPMPMT MIPPPWFPLP
MTQTFPPSFF PLISPGPHPS ISAALWKIHS ESMKTPIKQK VEQENVSLNT STCLSSPSIF
ITPTSDDRKL KRPSSPRSIT KSSETSINLI QETPESVESK RRRNVSITSS NSSSPTIWRP
F
