RUNX3_MOUSE
ID RUNX3_MOUSE Reviewed; 409 AA.
AC Q64131; B2FDG4; Q99P92; Q9R199;
DT 02-NOV-2001, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 3.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Runt-related transcription factor 3;
DE AltName: Full=Acute myeloid leukemia 2 protein;
DE AltName: Full=Core-binding factor subunit alpha-3;
DE Short=CBF-alpha-3;
DE AltName: Full=Oncogene AML-2;
DE AltName: Full=Polyomavirus enhancer-binding protein 2 alpha C subunit;
DE Short=PEA2-alpha C;
DE Short=PEBP2-alpha C;
DE AltName: Full=SL3-3 enhancer factor 1 alpha C subunit;
DE AltName: Full=SL3/AKV core-binding factor alpha C subunit;
GN Name=Runx3; Synonyms=Aml2, Cbfa3, Pebp2a3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Spleen;
RX PubMed=16651517; DOI=10.1073/pnas.0602470103;
RA Yarmus M., Woolf E., Bernstein Y., Fainaru O., Negreanu V., Levanon D.,
RA Groner Y.;
RT "Groucho/transducin-like Enhancer-of-split (TLE)-dependent and -independent
RT transcriptional regulation by Runx3.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:7384-7389(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 92-167.
RX PubMed=7607690; DOI=10.1016/0888-7543(95)80185-o;
RA Wijmenga C., Speck N.A., Dracopoli N.C., Hofker M.H., Liu P., Collins F.S.;
RT "Identification of a new murine runt domain-containing gene, Cbfa3, and
RT localization of the human homolog, CBFA3, to chromosome 1p35-pter.";
RL Genomics 26:611-614(1995).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-95 (ISOFORM 1).
RX PubMed=7607689; DOI=10.1016/0888-7543(95)80184-n;
RA Calabi F., Rhodes M., Williamson P., Boyd Y.;
RT "Identification and chromosomal mapping of a third mouse runt-like locus.";
RL Genomics 26:607-610(1995).
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-95 (ISOFORM 1).
RC STRAIN=129/Sv;
RA Negreanu V., Levanon D., Bettoun J.D., Groner Y.;
RT "The mouse AML2 gene - proximal promoter region.";
RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 2).
RX PubMed=11733147; DOI=10.1016/s0378-1119(01)00760-0;
RA Bangsow C., Rubins N., Glusman G., Bernstein Y., Negreanu V.,
RA Goldenberg D., Lotem J., Ben-Asher E., Lancet D., Levanon D., Groner Y.;
RT "The RUNX3 gene -- sequence, structure and regulated expression.";
RL Gene 279:221-232(2001).
RN [8]
RP FUNCTION.
RX PubMed=18258917; DOI=10.1126/science.1151844;
RA Setoguchi R., Tachibana M., Naoe Y., Muroi S., Akiyama K., Tezuka C.,
RA Okuda T., Taniuchi I.;
RT "Repression of the transcription factor Th-POK by Runx complexes in
RT cytotoxic T cell development.";
RL Science 319:822-825(2008).
RN [9]
RP FUNCTION, AND MUTAGENESIS OF 405-VAL--TYR-409.
RX PubMed=23481257; DOI=10.1038/emboj.2013.47;
RA Tanaka H., Naito T., Muroi S., Seo W., Chihara R., Miyamoto C.,
RA Kominami R., Taniuchi I.;
RT "Epigenetic Thpok silencing limits the time window to choose CD4(+) helper-
RT lineage fate in the thymus.";
RL EMBO J. 32:1183-1194(2013).
RN [10]
RP INTERACTION WITH TBX21.
RX PubMed=21151104; DOI=10.1038/ni.1969;
RA Lazarevic V., Chen X., Shim J.H., Hwang E.S., Jang E., Bolm A.N., Oukka M.,
RA Kuchroo V.K., Glimcher L.H.;
RT "T-bet represses T(H)17 differentiation by preventing Runx1-mediated
RT activation of the gene encoding RORgammat.";
RL Nat. Immunol. 12:96-104(2011).
CC -!- FUNCTION: Forms the heterodimeric complex core-binding factor (CBF)
CC with CBFB. RUNX members modulate the transcription of their target
CC genes through recognizing the core consensus binding sequence 5'-
CC TGTGGT-3', or very rarely, 5'-TGCGGT-3', within their regulatory
CC regions via their runt domain, while CBFB is a non-DNA-binding
CC regulatory subunit that allosterically enhances the sequence-specific
CC DNA-binding capacity of RUNX. The heterodimers bind to the core site of
CC a number of enhancers and promoters, including murine leukemia virus,
CC polyomavirus enhancer, T-cell receptor enhancers, LCK, IL3 and GM-CSF
CC promoters (Probable). May be involved in the control of cellular
CC proliferation and/or differentiation. In association with ZFHX3, up-
CC regulates CDKN1A promoter activity following TGF-beta stimulation (By
CC similarity). CBF complexes repress ZBTB7B transcription factor during
CC cytotoxic (CD8+) T cell development. They bind to RUNX-binding sequence
CC within the ZBTB7B locus acting as transcriptional silencer and allowing
CC for cytotoxic T cell differentiation (PubMed:18258917). CBF complexes
CC binding to the transcriptional silencer is essential for recruitment of
CC nuclear protein complexes that catalyze epigenetic modifications to
CC establish epigenetic ZBTB7B silencing (PubMed:23481257).
CC {ECO:0000250|UniProtKB:Q13761, ECO:0000269|PubMed:18258917,
CC ECO:0000269|PubMed:23481257, ECO:0000305}.
CC -!- SUBUNIT: Heterodimer with CBFB. RUNX3 binds DNA as a monomer and
CC through the Runt domain. DNA-binding is increased by heterodimerization
CC (Probable). Interacts with TLE1 and SUV39H1. The tyrosine
CC phosphorylated form (via runt domain) interacts with SRC (via protein
CC kinase domain). Interacts with FYN and LCK. Interacts with FOXP3.
CC Interacts with ZFHX3. Interacts with TBX21 (PubMed:21151104).
CC {ECO:0000250|UniProtKB:Q13761, ECO:0000269|PubMed:21151104,
CC ECO:0000305|PubMed:18258917}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q13761}. Cytoplasm
CC {ECO:0000250|UniProtKB:Q13761}. Note=The tyrosine phosphorylated form
CC localizes to the cytoplasm. Translocates from the cytoplasm to the
CC nucleus following TGF-beta stimulation. {ECO:0000250|UniProtKB:Q13761}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q64131-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q64131-2; Sequence=VSP_005950;
CC -!- DOMAIN: A proline/serine/threonine rich region at the C-terminus is
CC necessary for transcriptional activation of target genes.
CC -!- PTM: Phosphorylated on tyrosine residues by SRC. Phosphorylated by LCK
CC and FYN (By similarity). {ECO:0000250}.
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DR EMBL; AF155880; AAD38985.1; -; mRNA.
DR EMBL; AL731718; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CU459014; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CU459015; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH466552; EDL29993.1; -; Genomic_DNA.
DR EMBL; S78518; AAB34843.1; -; Genomic_DNA.
DR EMBL; AF169246; AAD46381.1; -; Genomic_DNA.
DR EMBL; AF321443; AAK11181.1; -; Genomic_DNA.
DR CCDS; CCDS18782.1; -. [Q64131-2]
DR CCDS; CCDS89843.1; -. [Q64131-1]
DR PIR; A56842; A56842.
DR PIR; A56843; A56843.
DR AlphaFoldDB; Q64131; -.
DR SMR; Q64131; -.
DR DIP; DIP-60276N; -.
DR ELM; Q64131; -.
DR IntAct; Q64131; 1.
DR STRING; 10090.ENSMUSP00000050353; -.
DR iPTMnet; Q64131; -.
DR PhosphoSitePlus; Q64131; -.
DR EPD; Q64131; -.
DR jPOST; Q64131; -.
DR MaxQB; Q64131; -.
DR PaxDb; Q64131; -.
DR PRIDE; Q64131; -.
DR ProteomicsDB; 256844; -. [Q64131-1]
DR ProteomicsDB; 256845; -. [Q64131-2]
DR Antibodypedia; 1124; 706 antibodies from 43 providers.
DR Ensembl; ENSMUST00000119564; ENSMUSP00000113159; ENSMUSG00000070691. [Q64131-1]
DR UCSC; uc008vgc.1; mouse. [Q64131-1]
DR MGI; MGI:102672; Runx3.
DR VEuPathDB; HostDB:ENSMUSG00000070691; -.
DR eggNOG; KOG3982; Eukaryota.
DR GeneTree; ENSGT00940000156598; -.
DR HOGENOM; CLU_032910_0_0_1; -.
DR InParanoid; Q64131; -.
DR Reactome; R-MMU-8941855; RUNX3 regulates CDKN1A transcription.
DR Reactome; R-MMU-8941856; RUNX3 regulates NOTCH signaling.
DR Reactome; R-MMU-8941858; Regulation of RUNX3 expression and activity.
DR Reactome; R-MMU-8951430; RUNX3 regulates WNT signaling.
DR Reactome; R-MMU-8951671; RUNX3 regulates YAP1-mediated transcription.
DR Reactome; R-MMU-8951936; RUNX3 regulates p14-ARF.
DR ChiTaRS; Runx3; mouse.
DR PRO; PR:Q64131; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q64131; protein.
DR Bgee; ENSMUSG00000070691; Expressed in intramembranous bone and 166 other tissues.
DR ExpressionAtlas; Q64131; baseline and differential.
DR Genevisible; Q64131; MM.
DR GO; GO:0000785; C:chromatin; IDA:BHF-UCL.
DR GO; GO:0016513; C:core-binding factor complex; TAS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0043231; C:intracellular membrane-bounded organelle; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR GO; GO:0003677; F:DNA binding; IDA:MGI.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:BHF-UCL.
DR GO; GO:0042826; F:histone deacetylase binding; ISO:MGI.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:BHF-UCL.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0001222; F:transcription corepressor binding; ISO:MGI.
DR GO; GO:0007411; P:axon guidance; IMP:MGI.
DR GO; GO:0048469; P:cell maturation; IGI:MGI.
DR GO; GO:0002062; P:chondrocyte differentiation; IGI:MGI.
DR GO; GO:0031069; P:hair follicle morphogenesis; IMP:MGI.
DR GO; GO:0030097; P:hemopoiesis; IBA:GO_Central.
DR GO; GO:0043371; P:negative regulation of CD4-positive, alpha-beta T cell differentiation; IMP:UniProtKB.
DR GO; GO:0045786; P:negative regulation of cell cycle; IMP:UniProtKB.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0031175; P:neuron projection development; IMP:MGI.
DR GO; GO:0001503; P:ossification; IBA:GO_Central.
DR GO; GO:0043378; P:positive regulation of CD8-positive, alpha-beta T cell differentiation; IMP:UniProtKB.
DR GO; GO:2001238; P:positive regulation of extrinsic apoptotic signaling pathway; IMP:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0045595; P:regulation of cell differentiation; IBA:GO_Central.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0071559; P:response to transforming growth factor beta; ISS: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 InterPro; IPR013711; RunxI_C_dom.
DR InterPro; IPR016554; TF_Runt-rel_RUNX.
DR PANTHER; PTHR11950; PTHR11950; 1.
DR Pfam; PF00853; Runt; 1.
DR Pfam; PF08504; RunxI; 1.
DR PIRSF; PIRSF009374; TF_Runt-rel_RUNX; 1.
DR PRINTS; PR00967; ONCOGENEAML1.
DR SUPFAM; SSF49417; SSF49417; 1.
DR PROSITE; PS51062; RUNT; 1.
PE 1: Evidence at protein level;
KW Activator; Alternative splicing; Cytoplasm; DNA-binding; Isopeptide bond;
KW Nucleus; Phosphoprotein; Reference proteome; Transcription;
KW Transcription regulation; Ubl conjugation.
FT CHAIN 1..409
FT /note="Runt-related transcription factor 3"
FT /id="PRO_0000174663"
FT DOMAIN 55..183
FT /note="Runt"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00399"
FT REGION 1..51
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 177..248
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 346..409
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 177..200
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 209..248
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 355..374
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 241
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q13761"
FT CROSSLNK 193
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q13761"
FT VAR_SEQ 1..5
FT /note="MRIPV -> MASNSIFDSFPQLYTNLHT (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_005950"
FT MUTAGEN 405..409
FT /note="Missing: Inhibits repression of ZBTB7B expression."
FT /evidence="ECO:0000269|PubMed:23481257"
FT CONFLICT 227..228
FT /note="AQ -> PK (in Ref. 1; AAD38985)"
FT /evidence="ECO:0000305"
FT CONFLICT 234..236
FT /note="SSD -> FLN (in Ref. 1; AAD38985)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 409 AA; 43518 MW; D2BCEBAF808A315D CRC64;
MRIPVDPSTS RRFTPPSTAF PCGGGGGGKM GENSGALSAQ ATAGPGGRTR PEVRSMVDVL
ADHAGELVRT DSPNFLCSVL PSHWRCNKTL PVAFKVVALG DVPDGTVVTV MAGNDENYSA
ELRNASAVMK NQVARFNDLR FVGRSGRGKS FTLTITVFTN PTQVATYHRA IKVTVDGPRE
PRRHRQKIED QTKAFPDRFG DLRMRVTPST PSPRGSLSTT SHFSSQAQTP IQGSSDLNPF
SDPRQFDRSF PTLQSLTESR FPDPRMHYPG AMSAAFPYSA TPSGTSLGSL SVAGMPASSR
FHHTYLPPPY PGAPQSQSGP FQANPAPYHL FYGASSGSYQ FSMAAAGGGE RSPTRMLTSC
PSGASVSAGN LMNPSLGQAD GVEADGSHSN SPTALSTPGR MDEAVWRPY
