RUNX1_RAT
ID RUNX1_RAT Reviewed; 450 AA.
AC Q63046;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 170.
DE RecName: Full=Runt-related transcription factor 1;
DE AltName: Full=Acute myeloid leukemia 1 protein;
DE AltName: Full=Core-binding factor subunit alpha-2;
DE Short=CBF-alpha-2;
DE AltName: Full=Oncogene AML-1;
DE AltName: Full=Polyomavirus enhancer-binding protein 2 alpha B subunit;
DE Short=PEA2-alpha B;
DE Short=PEBP2-alpha B;
GN Name=Runx1; Synonyms=Aml1, Cbfa2;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND INDUCTION.
RC STRAIN=Sprague-Dawley; TISSUE=Skeletal muscle;
RX PubMed=7969143; DOI=10.1128/mcb.14.12.8051-8057.1994;
RA Zhu X., Yeadon J.E., Burden S.J.;
RT "AML1 is expressed in skeletal muscle and is regulated by innervation.";
RL Mol. Cell. Biol. 14:8051-8057(1994).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-14 AND SER-21, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: CBF binds to the core site, 5'-PYGPYGGT-3', of a number of
CC enhancers and promoters, including murine leukemia virus, polyomavirus
CC enhancer, T-cell receptor enhancers, LCK, IL-3 and GM-CSF promoters.
CC The alpha subunit binds DNA and appears to have a role in the
CC development of normal hematopoiesis. Isoform AML-1L interferes with the
CC transactivation activity of RUNX1. Acts synergistically with ELF4 to
CC transactivate the IL-3 promoter and with ELF2 to transactivate the BLK
CC promoter. Inhibits KAT6B-dependent transcriptional activation. Controls
CC the anergy and suppressive function of regulatory T-cells (Treg) by
CC associating with FOXP3. Activates the expression of IL2 and IFNG and
CC down-regulates the expression of TNFRSF18, IL2RA and CTLA4, in
CC conventional T-cells (By similarity). Positively regulates the
CC expression of RORC in T-helper 17 cells (By similarity).
CC {ECO:0000250|UniProtKB:Q01196, ECO:0000250|UniProtKB:Q03347}.
CC -!- SUBUNIT: Heterodimer with CBFB. RUNX1 binds DNA as a monomer and
CC through the Runt domain. DNA-binding is increased by
CC heterodimerization. Interacts with TLE1 and ALYREF/THOC4. Interacts
CC with ELF1, ELF2 and SPI1. Interacts via its Runt domain with the ELF4
CC N-terminal region. Interaction with ELF2 isoform 2 (NERF-1a) may act to
CC repress RUNX1-mediated transactivation. Interacts with KAT6A and KAT6B.
CC Interacts with SUV39H1, leading to abrogation of transactivating and
CC DNA-binding properties of RUNX1. Interacts with YAP1 and HIPK2.
CC Interaction with CDK6 prevents myeloid differentiation, reducing its
CC transcription transactivation activity. Found in a complex with PRMT5,
CC RUNX1 and CBFB. Interacts with FOXP3. Interacts with TBX21. Interacts
CC with DPF2 (By similarity). {ECO:0000250|UniProtKB:Q01196,
CC ECO:0000250|UniProtKB:Q03347}.
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- TISSUE SPECIFICITY: Expressed in skeletal muscle.
CC {ECO:0000269|PubMed:7969143}.
CC -!- INDUCTION: Expression increases following denervation.
CC {ECO:0000269|PubMed:7969143}.
CC -!- DOMAIN: A proline/serine/threonine rich region at the C-terminus is
CC necessary for transcriptional activation of target genes.
CC -!- PTM: Phosphorylated in its C-terminus upon IL-6 treatment.
CC Phosphorylation enhances interaction with KAT6A (By similarity).
CC {ECO:0000250}.
CC -!- PTM: Methylated. {ECO:0000250}.
CC -!- PTM: Phosphorylated in Ser-249 Thr-272 and Ser-275 by HIPK2 when
CC associated with CBFB and DNA. This phosphorylation promotes subsequent
CC EP300 phosphorylation (By similarity). {ECO:0000250}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; L35271; AAA66191.1; -; mRNA.
DR RefSeq; NP_059021.1; NM_017325.2.
DR AlphaFoldDB; Q63046; -.
DR SMR; Q63046; -.
DR BioGRID; 248410; 1.
DR ELM; Q63046; -.
DR STRING; 10116.ENSRNOP00000002313; -.
DR iPTMnet; Q63046; -.
DR PhosphoSitePlus; Q63046; -.
DR PaxDb; Q63046; -.
DR PRIDE; Q63046; -.
DR Ensembl; ENSRNOT00000002313; ENSRNOP00000002313; ENSRNOG00000001704.
DR GeneID; 50662; -.
DR KEGG; rno:50662; -.
DR UCSC; RGD:2283; rat.
DR CTD; 861; -.
DR RGD; 2283; Runx1.
DR eggNOG; KOG3982; Eukaryota.
DR GeneTree; ENSGT00940000159255; -.
DR HOGENOM; CLU_032910_0_0_1; -.
DR InParanoid; Q63046; -.
DR PhylomeDB; Q63046; -.
DR Reactome; R-RNO-549127; Organic cation transport.
DR Reactome; R-RNO-8877330; RUNX1 and FOXP3 control the development of regulatory T lymphocytes (Tregs).
DR Reactome; R-RNO-8931987; RUNX1 regulates estrogen receptor mediated transcription.
DR Reactome; R-RNO-8934593; Regulation of RUNX1 Expression and Activity.
DR Reactome; R-RNO-8936459; RUNX1 regulates genes involved in megakaryocyte differentiation and platelet function.
DR Reactome; R-RNO-8939236; RUNX1 regulates transcription of genes involved in differentiation of HSCs.
DR Reactome; R-RNO-8939243; RUNX1 interacts with co-factors whose precise effect on RUNX1 targets is not known.
DR Reactome; R-RNO-8939245; RUNX1 regulates transcription of genes involved in BCR signaling.
DR Reactome; R-RNO-8939246; RUNX1 regulates transcription of genes involved in differentiation of myeloid cells.
DR Reactome; R-RNO-8939247; RUNX1 regulates transcription of genes involved in interleukin signaling.
DR Reactome; R-RNO-9018519; Estrogen-dependent gene expression.
DR PRO; PR:Q63046; -.
DR Proteomes; UP000002494; Chromosome 11.
DR Bgee; ENSRNOG00000001704; Expressed in thymus and 18 other tissues.
DR ExpressionAtlas; Q63046; baseline and differential.
DR Genevisible; Q63046; RN.
DR GO; GO:0005604; C:basement membrane; ISO:RGD.
DR GO; GO:0000785; C:chromatin; IDA:RGD.
DR GO; GO:0016513; C:core-binding factor complex; TAS:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR GO; GO:0003677; F:DNA binding; ISO:RGD.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:RGD.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0140297; F:DNA-binding transcription factor binding; ISO:RGD.
DR GO; GO:1990841; F:promoter-specific chromatin binding; IDA:RGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; ISO:RGD.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; IDA:RGD.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; ISO:RGD.
DR GO; GO:0001222; F:transcription corepressor binding; ISO:RGD.
DR GO; GO:0048266; P:behavioral response to pain; ISO:RGD.
DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; ISO:RGD.
DR GO; GO:0007417; P:central nervous system development; ISO:RGD.
DR GO; GO:0002062; P:chondrocyte differentiation; IBA:GO_Central.
DR GO; GO:0060216; P:definitive hemopoiesis; ISO:RGD.
DR GO; GO:0035162; P:embryonic hemopoiesis; ISO:RGD.
DR GO; GO:0031069; P:hair follicle morphogenesis; ISO:RGD.
DR GO; GO:0030097; P:hemopoiesis; ISO:RGD.
DR GO; GO:0001701; P:in utero embryonic development; ISO:RGD.
DR GO; GO:0001889; P:liver development; ISO:RGD.
DR GO; GO:0030099; P:myeloid cell differentiation; ISO:RGD.
DR GO; GO:0002573; P:myeloid leukocyte differentiation; ISO:RGD.
DR GO; GO:0002318; P:myeloid progenitor cell differentiation; ISO:RGD.
DR GO; GO:0043371; P:negative regulation of CD4-positive, alpha-beta T cell differentiation; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:RGD.
DR GO; GO:0048666; P:neuron development; ISO:RGD.
DR GO; GO:0030182; P:neuron differentiation; ISO:RGD.
DR GO; GO:0048663; P:neuron fate commitment; ISO:RGD.
DR GO; GO:0001503; P:ossification; IBA:GO_Central.
DR GO; GO:0030728; P:ovulation; IEP:RGD.
DR GO; GO:0045766; P:positive regulation of angiogenesis; ISS:UniProtKB.
DR GO; GO:0043378; P:positive regulation of CD8-positive, alpha-beta T cell differentiation; ISS:UniProtKB.
DR GO; GO:1903431; P:positive regulation of cell maturation; ISO:RGD.
DR GO; GO:0030854; P:positive regulation of granulocyte differentiation; ISS:UniProtKB.
DR GO; GO:0032729; P:positive regulation of interferon-gamma production; ISO:RGD.
DR GO; GO:0032743; P:positive regulation of interleukin-2 production; ISO:RGD.
DR GO; GO:2000872; P:positive regulation of progesterone secretion; IMP:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:RGD.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IMP:RGD.
DR GO; GO:0045595; P:regulation of cell differentiation; IBA:GO_Central.
DR GO; GO:0071336; P:regulation of hair follicle cell proliferation; ISO:RGD.
DR GO; GO:0009966; P:regulation of signal transduction; ISO:RGD.
DR GO; GO:0002667; P:regulation of T cell anergy; ISO:RGD.
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; ISO:RGD.
DR GO; GO:0014894; P:response to denervation involved in regulation of muscle adaptation; IEP:RGD.
DR GO; GO:0032526; P:response to retinoic acid; ISO:RGD.
DR GO; GO:0001501; P:skeletal system development; ISO:RGD.
DR Gene3D; 2.60.40.720; -; 1.
DR Gene3D; 4.10.770.10; -; 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; IPR027384; Runx_central_dom_sf.
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 Acetylation; Activator; DNA-binding; Methylation; Nucleus; Phosphoprotein;
KW Reference proteome; Repressor; Transcription; Transcription regulation.
FT CHAIN 1..450
FT /note="Runt-related transcription factor 1"
FT /id="PRO_0000174657"
FT DOMAIN 50..178
FT /note="Runt"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00399"
FT REGION 1..25
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 80..84
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT REGION 135..143
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT REGION 168..177
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT REGION 170..195
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 209..252
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 290..369
FT /note="Interaction with KAT6A"
FT /evidence="ECO:0000250"
FT REGION 306..398
FT /note="Interaction with KAT6B"
FT /evidence="ECO:0000250"
FT REGION 360..400
FT /note="Interaction with FOXP3"
FT /evidence="ECO:0000250|UniProtKB:Q01196"
FT REGION 410..450
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 170..186
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 222..252
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 410..438
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 112
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00399"
FT BINDING 116
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00399"
FT BINDING 139
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00399"
FT BINDING 170
FT /ligand="chloride"
FT /ligand_id="ChEBI:CHEBI:17996"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00399"
FT MOD_RES 14
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 21
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 24
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q01196"
FT MOD_RES 43
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q01196"
FT MOD_RES 193
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01196"
FT MOD_RES 212
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01196"
FT MOD_RES 249
FT /note="Phosphoserine; by HIPK2"
FT /evidence="ECO:0000250|UniProtKB:Q01196"
FT MOD_RES 266
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01196"
FT MOD_RES 267
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01196"
FT MOD_RES 272
FT /note="Phosphothreonine; by HIPK2"
FT /evidence="ECO:0000250|UniProtKB:Q01196"
FT MOD_RES 275
FT /note="Phosphoserine; by HIPK2"
FT /evidence="ECO:0000250|UniProtKB:Q01196"
FT MOD_RES 295
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q01196"
FT MOD_RES 433
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q01196"
SQ SEQUENCE 450 AA; 48556 MW; 4B53AD706D487AC3 CRC64;
MRIPVDASTS RRFTPPSTAL SPGKMSEALP LGAPDGGAAL ASKLRSGDRS MVEVLADHPG
ELVRTDSPNF LCSVLPTHWR CNKTLPIAFK VVALGDVPDG TLVTVMAGND ENYSAELRNA
TAAMKNQVAR FNDLRFVGRS GRGKSFTLTI TVFTNPPQVA TYHRAIKITV DGPREPRRHR
QKLDDQTKPG SLSFSERLSE LEQLRRTAMR VSPHHPAPTP NPRASLNHST AFNPQPQSQM
QDARQIQPSP PWSYDQSYQY LGSITSSVHP ATPISPGRAS GMTSLSAELS SRLSTAPDLT
AFGDPRQFPT LPSISDPRMH YPGAFTYSPP VTSGIGIGMS AMSSTSRYHT YLPPPYPGSS
QAQAGPFQTG SPSYHLYYGT SAGSYQFSMV GGERSPPRIL PPCTNASTGA ALLNPSLPSQ
SDVVETEGSH SNSPTNMPPA RLEEAVWRPY
