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Protein

Runt-related transcription factor 3

Gene

Runx3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Forms the heterodimeric complex core-binding factor (CBF) with CBFB. RUNX members modulate the transcription of their target genes through recognizing the core consensus binding sequence 5'-TGTGGT-3', or very rarely, 5'-TGCGGT-3', within their regulatory regions via their runt domain, while CBFB is a non-DNA-binding regulatory subunit that allosterically enhances the sequence-specific DNA-binding capacity of RUNX. The heterodimers bind to the core site of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, LCK, IL3 and GM-CSF promoters (Probable). May be involved in the control of cellular proliferation and/or differentiation. In association with ZFHX3, upregulates CDKN1A promoter activity following TGF-beta stimulation (By similarity). CBF complexes repress ZBTB7B transcription factor during cytotoxic (CD8+) T cell development. They bind to RUNX-binding sequence within the ZBTB7B locus acting as transcriptional silencer and allowing for cytotoxic T cell differentiation (PubMed:18258917). CBF complexes binding to the transcriptional silencer is essential for recruitment of nuclear protein complexes that catalyze epigenetic modifications to establish epigenetic ZBTB7B silencing (PubMed:23481257).By similarityCurated2 Publications

GO - Molecular functioni

  • ATP binding Source: InterPro
  • DNA binding Source: MGI
  • histone deacetylase binding Source: MGI
  • RNA polymerase II regulatory region sequence-specific DNA binding Source: BHF-UCL
  • RNA polymerase II transcription factor activity, sequence-specific DNA binding Source: BHF-UCL
  • SMAD binding Source: MGI

GO - Biological processi

  • axon guidance Source: MGI
  • cell maturation Source: MGI
  • chondrocyte differentiation Source: MGI
  • hair follicle morphogenesis Source: MGI
  • hemopoiesis Source: GO_Central
  • interferon-gamma production Source: MGI
  • mRNA transcription by RNA polymerase II Source: BHF-UCL
  • negative regulation of CD4-positive, alpha-beta T cell differentiation Source: UniProtKB
  • negative regulation of cell cycle Source: UniProtKB
  • negative regulation of epithelial cell proliferation Source: UniProtKB
  • negative regulation of transcription by RNA polymerase II Source: UniProtKB
  • neuron projection development Source: MGI
  • ossification Source: GO_Central
  • positive regulation of CD8-positive, alpha-beta T cell differentiation Source: UniProtKB
  • positive regulation of extrinsic apoptotic signaling pathway Source: MGI
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription by RNA polymerase II Source: MGI
  • protein phosphorylation Source: UniProtKB
  • regulation of cell differentiation Source: GO_Central
  • response to transforming growth factor beta Source: UniProtKB

Keywordsi

Molecular functionActivator, DNA-binding
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-MMU-8941855 RUNX3 regulates CDKN1A transcription
R-MMU-8941856 RUNX3 regulates NOTCH signaling
R-MMU-8941858 Regulation of RUNX3 expression and activity
R-MMU-8951430 RUNX3 regulates WNT signaling
R-MMU-8951671 RUNX3 regulates YAP1-mediated transcription
R-MMU-8951936 RUNX3 regulates p14-ARF

Names & Taxonomyi

Protein namesi
Recommended name:
Runt-related transcription factor 3
Alternative name(s):
Acute myeloid leukemia 2 protein
Core-binding factor subunit alpha-3
Short name:
CBF-alpha-3
Oncogene AML-2
Polyomavirus enhancer-binding protein 2 alpha C subunit
Short name:
PEA2-alpha C
Short name:
PEBP2-alpha C
SL3-3 enhancer factor 1 alpha C subunit
SL3/AKV core-binding factor alpha C subunit
Gene namesi
Name:Runx3
Synonyms:Aml2, Cbfa3, Pebp2a3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 4

Organism-specific databases

MGIiMGI:102672 Runx3

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi405 – 409Missing : Inhibits repression of ZBTB7B expression. 1 Publication5

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001746631 – 409Runt-related transcription factor 3Add BLAST409

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki193Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei241PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated on tyrosine residues by SRC. Phosphorylated by LCK and FYN (By similarity).By similarity

Keywords - PTMi

Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiQ64131
PaxDbiQ64131
PRIDEiQ64131

PTM databases

iPTMnetiQ64131
PhosphoSitePlusiQ64131

Expressioni

Gene expression databases

BgeeiENSMUSG00000070691
CleanExiMM_RUNX3
ExpressionAtlasiQ64131 baseline and differential
GenevisibleiQ64131 MM

Interactioni

Subunit structurei

Heterodimer with CBFB. RUNX3 binds DNA as a monomer and through the Runt domain. DNA-binding is increased by heterodimerization (Probable). Interacts with TLE1 and SUV39H1. The tyrosine phosphorylated form (via runt domain) interacts with SRC (via protein kinase domain). Interacts with FYN and LCK. Interacts with FOXP3. Interacts with ZFHX3. Interacts with TBX21 (PubMed:21151104).By similarity1 Publication1 Publication

GO - Molecular functioni

Protein-protein interaction databases

DIPiDIP-60276N
ELMiQ64131
IntActiQ64131, 1 interactor
STRINGi10090.ENSMUSP00000050353

Structurei

3D structure databases

ProteinModelPortaliQ64131
SMRiQ64131
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini55 – 183RuntPROSITE-ProRule annotationAdd BLAST129

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi23 – 28Poly-Gly6

Domaini

A proline/serine/threonine rich region at the C-terminus is necessary for transcriptional activation of target genes.

Phylogenomic databases

eggNOGiKOG3982 Eukaryota
ENOG4111J4Y LUCA
GeneTreeiENSGT00390000016964
HOGENOMiHOG000045616
HOVERGENiHBG060268
InParanoidiQ64131

Family and domain databases

Gene3Di2.60.40.720, 1 hit
InterProiView protein in InterPro
IPR000040 AML1_Runt
IPR008967 p53-like_TF_DNA-bd
IPR012346 p53/RUNT-type_TF_DNA-bd_sf
IPR013524 Runt_dom
IPR013711 RunxI_C_dom
IPR016554 TF_Runt-rel_RUNX
PANTHERiPTHR11950 PTHR11950, 1 hit
PfamiView protein in Pfam
PF00853 Runt, 1 hit
PF08504 RunxI, 1 hit
PIRSFiPIRSF009374 TF_Runt-rel_RUNX, 1 hit
PRINTSiPR00967 ONCOGENEAML1
SUPFAMiSSF49417 SSF49417, 1 hit
PROSITEiView protein in PROSITE
PS51062 RUNT, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q64131-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRIPVDPSTS RRFTPPSTAF PCGGGGGGKM GENSGALSAQ ATAGPGGRTR
60 70 80 90 100
PEVRSMVDVL ADHAGELVRT DSPNFLCSVL PSHWRCNKTL PVAFKVVALG
110 120 130 140 150
DVPDGTVVTV MAGNDENYSA ELRNASAVMK NQVARFNDLR FVGRSGRGKS
160 170 180 190 200
FTLTITVFTN PTQVATYHRA IKVTVDGPRE PRRHRQKIED QTKAFPDRFG
210 220 230 240 250
DLRMRVTPST PSPRGSLSTT SHFSSQAQTP IQGSSDLNPF SDPRQFDRSF
260 270 280 290 300
PTLQSLTESR FPDPRMHYPG AMSAAFPYSA TPSGTSLGSL SVAGMPASSR
310 320 330 340 350
FHHTYLPPPY PGAPQSQSGP FQANPAPYHL FYGASSGSYQ FSMAAAGGGE
360 370 380 390 400
RSPTRMLTSC PSGASVSAGN LMNPSLGQAD GVEADGSHSN SPTALSTPGR

MDEAVWRPY
Length:409
Mass (Da):43,518
Last modified:July 27, 2011 - v3
Checksum:iD2BCEBAF808A315D
GO
Isoform 2 (identifier: Q64131-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-5: MRIPV → MASNSIFDSFPQLYTNLHT

Show »
Length:423
Mass (Da):45,089
Checksum:i61F218AB7DC04D52
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti227 – 228AQ → PK in AAD38985 (PubMed:16651517).Curated2
Sequence conflicti234 – 236SSD → FLN in AAD38985 (PubMed:16651517).Curated3

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0059501 – 5MRIPV → MASNSIFDSFPQLYTNLHT in isoform 2. Curated5

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF155880 mRNA Translation: AAD38985.1
AL731718 Genomic DNA Translation: CAQ51606.1
CU459015 Genomic DNA Translation: CAQ52301.1
CU459014 Genomic DNA Translation: CAQ52315.1
CH466552 Genomic DNA Translation: EDL29993.1
S78518 Genomic DNA Translation: AAB34843.1
AF169246 Genomic DNA Translation: AAD46381.1
AF321443 Genomic DNA Translation: AAK11181.1
CCDSiCCDS18782.1 [Q64131-2]
PIRiA56842
A56843
UniGeneiMm.378894

Genome annotation databases

EnsembliENSMUST00000119564; ENSMUSP00000113159; ENSMUSG00000070691 [Q64131-1]
UCSCiuc008vgc.1 mouse [Q64131-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiRUNX3_MOUSE
AccessioniPrimary (citable) accession number: Q64131
Secondary accession number(s): B2FDG4, Q99P92, Q9R199
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 2, 2001
Last sequence update: July 27, 2011
Last modified: May 23, 2018
This is version 150 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot

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