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Protein

Runt-related transcription factor 3

Gene

RUNX3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

CBF binds to the core site, 5'-PYGPYGGT-3', of a number of enhancers and promoters, including murine leukemia virus, polyomavirus enhancer, T-cell receptor enhancers, lck, IL-3 and GM-CSF promoters. In association with ZFHX3, upregulates CDKN1A promoter activity following TGF-beta stimulation (PubMed:20599712).1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding
Biological processTranscription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-HSA-4411364. Binding of TCF/LEF:CTNNB1 to target gene promoters.
R-HSA-8941855. RUNX3 regulates CDKN1A transcription.
R-HSA-8941856. RUNX3 regulates NOTCH signaling.
R-HSA-8941858. Regulation of RUNX3 expression and activity.
R-HSA-8949275. RUNX3 Regulates Immune Response and Cell Migration.
R-HSA-8951430. RUNX3 regulates WNT signaling.
R-HSA-8951671. RUNX3 regulates YAP1-mediated transcription.
R-HSA-8951911. RUNX3 regulates RUNX1-mediated transcription.
R-HSA-8951936. RUNX3 regulates p14-ARF.
R-HSA-8952158. RUNX3 regulates BCL2L11 (BIM) transcription.
SIGNORiQ13761.

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
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:10473. RUNX3.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • cytosol Source: HPA
  • intracellular membrane-bounded organelle Source: HPA
  • nuclear chromatin Source: BHF-UCL
  • nucleolus Source: HPA
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Organism-specific databases

DisGeNETi864.
OpenTargetsiENSG00000020633.
PharmGKBiPA34886.

Polymorphism and mutation databases

BioMutaiRUNX3.
DMDMi17368453.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001746621 – 415Runt-related transcription factor 3Add BLAST415

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei243PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated on tyrosine residues by SRC. Phosphorylated by LCK and FYN.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ13761.
MaxQBiQ13761.
PaxDbiQ13761.
PeptideAtlasiQ13761.
PRIDEiQ13761.

PTM databases

iPTMnetiQ13761.
PhosphoSitePlusiQ13761.
SwissPalmiQ13761.

Expressioni

Tissue specificityi

Expressed in gastric cancer tissues (at protein level).1 Publication

Gene expression databases

BgeeiENSG00000020633.
CleanExiHS_RUNX3.
ExpressionAtlasiQ13761. baseline and differential.
GenevisibleiQ13761. HS.

Organism-specific databases

HPAiCAB025416.
HPA004195.
HPA059006.

Interactioni

Subunit structurei

Heterodimer of an alpha and a beta subunit. The alpha subunit binds DNA as a monomer and through the Runt domain. DNA-binding is increased by heterodimerization. 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 ZFHX3.5 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi107312. 25 interactors.
IntActiQ13761. 17 interactors.
MINTiMINT-6774046.
STRINGi9606.ENSP00000343477.

Structurei

3D structure databases

ProteinModelPortaliQ13761.
SMRiQ13761.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini54 – 182RuntPROSITE-ProRule annotationAdd BLAST129

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi23 – 27Poly-Gly5
Compositional biasi191 – 415Pro/Ser/Thr-richAdd BLAST225

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.
InParanoidiQ13761.
KOiK09279.
OMAiGPFQANP.
PhylomeDBiQ13761.
TreeFamiTF321496.

Family and domain databases

Gene3Di2.60.40.720. 1 hit.
4.10.770.10. 1 hit.
InterProiView protein in InterPro
IPR000040. AML1_Runt.
IPR008967. p53-like_TF_DNA-bd.
IPR012346. p53/RUNT-type_TF_DNA-bd.
IPR013524. Runt_dom.
IPR027384. Runx_central_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. 2 hits.
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: Q13761-1) [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 RRFTPPSPAF PCGGGGGKMG ENSGALSAQA AVGPGGRARP
60 70 80 90 100
EVRSMVDVLA DHAGELVRTD SPNFLCSVLP SHWRCNKTLP VAFKVVALGD
110 120 130 140 150
VPDGTVVTVM AGNDENYSAE LRNASAVMKN QVARFNDLRF VGRSGRGKSF
160 170 180 190 200
TLTITVFTNP TQVATYHRAI KVTVDGPREP RRHRQKLEDQ TKPFPDRFGD
210 220 230 240 250
LERLRMRVTP STPSPRGSLS TTSHFSSQPQ TPIQGTSELN PFSDPRQFDR
260 270 280 290 300
SFPTLPTLTE SRFPDPRMHY PGAMSAAFPY SATPSGTSIS SLSVAGMPAT
310 320 330 340 350
SRFHHTYLPP PYPGAPQNQS GPFQANPSPY HLYYGTSSGS YQFSMVAGSS
360 370 380 390 400
SGGDRSPTRM LASCTSSAAS VAAGNLMNPS LGGQSDGVEA DGSHSNSPTA
410
LSTPGRMDEA VWRPY
Length:415
Mass (Da):44,356
Last modified:November 1, 1999 - v2
Checksum:i593FBFB3C4639BBD
GO
Isoform 2 (identifier: Q13761-2) [UniParc]FASTAAdd to basket

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

Show »
Length:429
Mass (Da):45,922
Checksum:iE9A43E96EDF82389
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti249D → V in CAA56093 (PubMed:7835892).Curated1
Sequence conflicti253P → S in CAA56093 (PubMed:7835892).Curated1
Sequence conflicti256P → S in CAA56093 (PubMed:7835892).Curated1
Sequence conflicti259T → S in CAA56093 (PubMed:7835892).Curated1
Sequence conflicti268 – 269MH → IY in CAA56093 (PubMed:7835892).Curated2
Sequence conflicti271P → T in CAA56093 (PubMed:7835892).Curated1
Sequence conflicti297 – 298MP → IS in CAA56093 (PubMed:7835892).Curated2

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0059491 – 5MRIPV → MASNSIFDSFPTYSPTFIR in isoform 2. 1 Publication5

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
Z35278 mRNA. Translation: CAA84541.1.
X79550 mRNA. Translation: CAA56093.2.
AL023096 Genomic DNA. Translation: CAA18856.1.
AL445471, AL023096 Genomic DNA. Translation: CAC42093.2.
AL023096, AL445471 Genomic DNA. Translation: CAI20422.1.
CH471134 Genomic DNA. Translation: EAW95148.1.
BC013362 mRNA. Translation: AAH13362.1.
U14520 Genomic DNA. Translation: AAA86465.1.
CCDSiCCDS257.1. [Q13761-1]
CCDS30633.1. [Q13761-2]
PIRiB55563.
S60078.
RefSeqiNP_001026850.1. NM_001031680.2. [Q13761-2]
NP_001307601.1. NM_001320672.1. [Q13761-2]
NP_004341.1. NM_004350.2. [Q13761-1]
XP_005246081.1. XM_005246024.4. [Q13761-2]
UniGeneiHs.170019.

Genome annotation databases

EnsembliENST00000308873; ENSP00000308051; ENSG00000020633. [Q13761-1]
ENST00000338888; ENSP00000343477; ENSG00000020633. [Q13761-2]
ENST00000399916; ENSP00000382800; ENSG00000020633. [Q13761-2]
GeneIDi864.
KEGGihsa:864.
UCSCiuc001bjq.4. human. [Q13761-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiRUNX3_HUMAN
AccessioniPrimary (citable) accession number: Q13761
Secondary accession number(s): B1AJV5, Q12969, Q13760
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 2, 2001
Last sequence update: November 1, 1999
Last modified: July 5, 2017
This is version 179 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot