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Q03347 (RUNX1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 142. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Runt-related transcription factor 1
Alternative name(s):
Acute myeloid leukemia 1 protein
Core-binding factor subunit alpha-2
Short name=CBF-alpha-2
Oncogene AML-1
Polyomavirus enhancer-binding protein 2 alpha B subunit
Short name=PEA2-alpha B
Short name=PEBP2-alpha B
SL3-3 enhancer factor 1 alpha B subunit
SL3/AKV core-binding factor alpha B subunit
Gene names
Name:Runx1
Synonyms:Aml1, Cbfa2, Pebp2ab
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length451 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Essential for the development of normal hematopoiesis. Isoform 4 shows higher binding activities for target genes and binds TCR-beta-E2 and RAG-1 target site with threefold higher affinity than other isoforms. It is less effective in the context of neutrophil terminal differentiation. Acts synergistically with ELF4 to transactivate the IL-3 promoter and with ELF2 to transactivate the BLK promoter. Inhibits KAT6B-dependent transcriptional activation By similarity. Ref.7 Ref.9

Subunit structure

Heterodimer with CBFB. RUNX1 binds DNA as a monomer and through the Runt domain. DNA-binding is increased by heterodimerization. Interacts with TLE1 and ALYREF/THOC4. Interacts with HIPK2, ELF1, ELF2 and SPI1. Interacts via its Runt domain with the ELF4 N-terminal region. Interaction with ELF2 isoform 2 (NERF-1a) may act to repress RUNX1-mediated transactivation. Interacts with KAT6A and KAT6B. Interacts with SUV39H1, leading to abrogation of transactivating and DNA-binding properties of RUNX1 By similarity. Interacts with YAP1. Interaction with CDK6 prevents myeloid differentiation, reducing its transcription transactivation activity By similarity. Found in a complex with PRMT5, RUNX1 and CBFB. Ref.8 Ref.10

Subcellular location

Nucleus.

Tissue specificity

Isoform 4 is expressed at high levels in thymus, spleen and T-cell lines and at lower levels in myeloid cell lines and nonhematopoietic cells. Isoform 5 is expressed ubiquitously in lumbar vertebrae, brain, kidney, heart, muscle, ovary and osteoblast-like cell line MC3T3-E1.

Developmental stage

Differentially expressed during hematopoietic differentiation. Isoform AML1-Bis readily detectable in undifferentiated embryonic stem (es) cells and peak expression is seen on day 6 of differentiation, followed by a gradual decline thereafter. Isoform AML1-Cis undetectable in undifferentiated es cells, but is gradually up-regulated along with differentiation and reaches its highest levels on day 8 and this expression is maintained through day 12. Isoform 5 is expressed at high levels at 6-8 dpc and then levels decrease on 12 dpc. Isoform 4 expression is high throughout T-cell development, declines with natural killer cell maturation, and appears to be transiently reduced and then restored during B-cell development.

Domain

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

Post-translational modification

Phosphorylated in its C-terminus upon IL-6 treatment. Phosphorylation enhances interaction with KAT6A By similarity. Ref.10

Methylated By similarity.

Phosphorylated in Ser-249 Thr-273 and Ser-276 by HIPK2 when associated with CBFB and DNA. This phosphorylation promotes subsequent EP300 phosphorylation. Ref.10

Involvement in disease

Mice with an Runx1 lacking the DNA-binding region are found to die between embryonic days 11.5 to 12.5 due to hemorrhaging in the central nervous system. This hemorrhaging is preceded by necrosis and hematopoiesis is blocked.

Sequence similarities

Contains 1 Runt domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   LigandDNA-binding
   PTMAcetylation
Methylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processbehavioral response to pain

Inferred from mutant phenotype PubMed 16446141. Source: MGI

central nervous system development

Inferred from mutant phenotype PubMed 16174759. Source: MGI

definitive hemopoiesis

Inferred from mutant phenotype PubMed 10207104. Source: MGI

embryonic hemopoiesis

Inferred from mutant phenotype PubMed 16174759. Source: MGI

hair follicle morphogenesis

Inferred from mutant phenotype PubMed 17011173. Source: MGI

hemopoiesis

Traceable author statement PubMed 10207087. Source: UniProtKB

in utero embryonic development

Inferred from mutant phenotype PubMed 16174759. Source: MGI

liver development

Inferred from mutant phenotype PubMed 16174759. Source: MGI

myeloid progenitor cell differentiation

Inferred from mutant phenotype PubMed 19182774. Source: MGI

neuron development

Inferred from mutant phenotype PubMed 16446141. Source: MGI

neuron differentiation

Inferred from mutant phenotype PubMed 15240886. Source: MGI

positive regulation of angiogenesis

Inferred from mutant phenotype PubMed 10943840. Source: UniProtKB

positive regulation of granulocyte differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription from RNA polymerase II promoter

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of transcription, DNA-templated

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of hair follicle cell proliferation

Inferred from mutant phenotype PubMed 21464233. Source: MGI

regulation of signal transduction

Inferred from mutant phenotype PubMed 21464233. Source: MGI

regulation of transcription, DNA-templated

Inferred from direct assay PubMed 12807883. Source: MGI

response to retinoic acid

Inferred from direct assay PubMed 18439490. Source: BHF-UCL

skeletal system development

Inferred from mutant phenotype PubMed 15389629. Source: MGI

transcription, DNA-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentbasement membrane

Inferred from direct assay PubMed 17011173. Source: MGI

nucleus

Inferred from direct assay PubMed 21464233. Source: MGI

   Molecular_functionATP binding

Inferred from electronic annotation. Source: InterPro

DNA binding

Inferred from direct assay PubMed 7774816. Source: UniProtKB

repressing transcription factor binding

Inferred from physical interaction PubMed 12551949. Source: MGI

sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 12807883. Source: MGI

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

Tbx21Q9JKD83EBI-3863873,EBI-3863870

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q03347-1)

Also known as: AML1-B; PEB2-alpha B1;

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.
Isoform 2 (identifier: Q03347-2)

Also known as: PEB2-alpha B2;

The sequence of this isoform differs from the canonical sequence as follows:
     178-178: R → N
     179-242: Missing.
Isoform 3 (identifier: Q03347-3)

The sequence of this isoform differs from the canonical sequence as follows:
     92-182: VALGDVPDGT...PREPRRHRQK → LLPEEGGGRS...ASEVSKREFF
     183-451: Missing.
Isoform 4 (identifier: Q03347-4)

Also known as: AML1-C;

The sequence of this isoform differs from the canonical sequence as follows:
     1-5: MRIPV → MASDSIFESFPSYPQCFMR
Isoform 5 (identifier: Q03347-5)

The sequence of this isoform differs from the canonical sequence as follows:
     242-303: DARQIQPSPP...LSTAPDLTAF → KNPTEPTTLC...EYLYSEKCGC
     304-451: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 451451Runt-related transcription factor 1
PRO_0000174656

Regions

Domain50 – 178129Runt
Region80 – 845Interaction with DNA By similarity
Region135 – 1439Interaction with DNA By similarity
Region168 – 17710Interaction with DNA By similarity
Region291 – 37080Interaction with KAT6A By similarity
Region307 – 39993Interaction with KAT6B By similarity
Compositional bias187 – 451265Pro/Ser/Thr-rich

Sites

Binding site1121Chloride 1 By similarity
Binding site1161Chloride 1; via amide nitrogen By similarity
Binding site1391Chloride 2 By similarity
Binding site1701Chloride 2; via amide nitrogen By similarity

Amino acid modifications

Modified residue141Phosphothreonine By similarity
Modified residue211Phosphoserine By similarity
Modified residue241N6-acetyllysine By similarity
Modified residue431N6-acetyllysine By similarity
Modified residue2491Phosphoserine; by HIPK2 Ref.10
Modified residue2661Phosphoserine By similarity
Modified residue2681Phosphoserine By similarity
Modified residue2731Phosphothreonine; by HIPK2 By similarity
Modified residue2761Phosphoserine; by HIPK2 Ref.10

Natural variations

Alternative sequence1 – 55MRIPV → MASDSIFESFPSYPQCFMR in isoform 4.
VSP_005930
Alternative sequence92 – 18291VALGD…RHRQK → LLPEEGGGRSRWRSADGQSE PRGQRLRRLLKGAACSRSLW SFSLSLGWGGDAALPWRPSG GSASEVSKREFF in isoform 3.
VSP_005931
Alternative sequence1781R → N in isoform 2.
VSP_005932
Alternative sequence179 – 24264Missing in isoform 2.
VSP_005933
Alternative sequence183 – 451269Missing in isoform 3.
VSP_005934
Alternative sequence242 – 30362DARQI…DLTAF → KNPTEPTTLCLCWSPRRRKH RGCQAFLGALRELLKPRSIS WEPNEENAVPSAEYLYSEKC GC in isoform 5.
VSP_005935
Alternative sequence304 – 451148Missing in isoform 5.
VSP_005936

Experimental info

Mutagenesis801R → A: Interferes with DNA-binding. Ref.12
Mutagenesis1091N → A: Interferes with heterodimerization. Ref.12
Mutagenesis1131Y → A: Interferes with heterodimerization. Ref.12
Mutagenesis1421R → A: Interferes with DNA-binding. Ref.12
Mutagenesis1441K → M: Interferes with DNA-binding. Ref.12
Mutagenesis1491T → A: Interferes with heterodimerization. Ref.12
Mutagenesis1701V → A: No effect. Ref.12
Mutagenesis1711D → A: Interferes with DNA-binding. Ref.12
Mutagenesis1741R → A: Interferes with DNA-binding. Ref.12
Mutagenesis1771R → A: Interferes with DNA-binding. Ref.12
Mutagenesis2491S → A: Reduced phosphorylation. Ref.10
Mutagenesis2761S → A: Reduced phosphorylation. Ref.10
Sequence conflict37 – 382GP → A in CAA65976. Ref.3

Secondary structure

............................... 451
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (AML1-B) (PEB2-alpha B1) [UniParc].

Last modified November 1, 1996. Version 1.
Checksum: 06B9E9BA01A6469C

FASTA45148,610
        10         20         30         40         50         60 
MRIPVDASTS RRFTPPSTAL SPGKMSEALP LGAPDGGPAL ASKLRSGDRS MVEVLADHPG 

        70         80         90        100        110        120 
ELVRTDSPNF LCSVLPTHWR CNKTLPIAFK VVALGDVPDG TLVTVMAGND ENYSAELRNA 

       130        140        150        160        170        180 
TAAMKNQVAR FNDLRFVGRS GRGKSFTLTI TVFTNPPQVA TYHRAIKITV DGPREPRRHR 

       190        200        210        220        230        240 
QKLDDQTKPG SLSFSERLSE LEQLRRTAMR VSPHHPAPTP NPRASLNHST AFNPQPQSQM 

       250        260        270        280        290        300 
QDARQIQPSP PWSYDQSYQY LGSITSSSVH PATPISPGRA SGMTSLSAEL SSRLSTAPDL 

       310        320        330        340        350        360 
TAFGDPRQFP TLPSISDPRM HYPGAFTYSP PVTSGIGIGM SAMSSASRYH TYLPPPYPGS 

       370        380        390        400        410        420 
SQAQAGPFQT GSPSYHLYYG ASAGSYQFSM VGGERSPPRI LPPCTNASTG AALLNPSLPS 

       430        440        450 
QSDVVETEGS HSNSPTNMPP ARLEEAVWRP Y 

« Hide

Isoform 2 (PEB2-alpha B2) [UniParc].

Checksum: CB505325F9D4ED81
Show »

FASTA38741,299
Isoform 3 [UniParc].

Checksum: AE48F53C5FF9A096
Show »

FASTA16317,571
Isoform 4 (AML1-C) [UniParc].

Checksum: 8C7E357BAA92E2E5
Show »

FASTA46550,238
Isoform 5 [UniParc].

Checksum: ED89962B59A0EC94
Show »

FASTA30333,485

References

[1]"Isolation of PEBP2 alpha B cDNA representing the mouse homolog of human acute myeloid leukemia gene, AML1."
Bae S.-C., Yamaguchi-Iwai Y., Ogawa E., Maruyama M., Inuzuka M., Kagoshima H., Shigesada K., Satake M., Ito Y.
Oncogene 8:809-814(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Fibroblast.
[2]"PEBP2 alpha B/mouse AML1 consists of multiple isoforms that possess differential transactivation potentials."
Bae S.-C., Ogawa E., Maruyama M., Oka H., Satake M., Shigesada K., Jenkins N.A., Gilbert D.J., Copeland N.G., Ito Y.
Mol. Cell. Biol. 14:3242-3252(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Fibroblast.
[3]Calabi F.
Submitted (APR-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3).
Strain: BALB/c.
Tissue: Thymus.
[4]"Identification and expression of a novel 3'-exon of mouse Runx1/Pebp2alphaB/Cbfa2/AML1 gene."
Tsuji K., Noda M.
Biochem. Biophys. Res. Commun. 274:171-176(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
[5]"Identification of an alternatively spliced form of the mouse AML1/RUNX1 gene transcript AML1c and its expression in early hematopoietic development."
Fujita Y., Nishimura M., Taniwaki M., Abe T., Okuda T.
Biochem. Biophys. Res. Commun. 281:1248-1255(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4).
Strain: 129/Ola.
Tissue: Embryo.
[6]"Expression and function of a stem cell promoter for the murine CBFalpha2 gene: distinct roles and regulation in natural killer and T cell development."
Telfer J.C., Rothenberg E.V.
Dev. Biol. 229:363-382(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORM 4).
Strain: C57BL/6.
Tissue: Thymus.
[7]"AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis."
Okuda T., van Deursen J., Hiebert S.W., Grosveld G., Downing J.R.
Cell 84:321-330(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN LIVER HEMATOPOIESIS.
[8]"The histone- and PRMT5-associated protein COPR5 is required for myogenic differentiation."
Paul C., Sardet C., Fabbrizio E.
Cell Death Differ. 19:900-908(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH PRMT5; RUNX1 AND CBFB.
[9]"Disruption of the Cbfa2 gene causes necrosis and hemorrhaging in the central nervous system and blocks definitive hematopoiesis."
Wang Q., Stacy T., Binder M., Marin-Padilla M., Sharpe A.H., Speck N.A.
Proc. Natl. Acad. Sci. U.S.A. 93:3444-3449(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN NECROSIS AND HEMORRHAGING.
[10]"Roles of HIPK1 and HIPK2 in AML1- and p300-dependent transcription, hematopoiesis and blood vessel formation."
Aikawa Y., Nguyen L.A., Isono K., Takakura N., Tagata Y., Schmitz M.L., Koseki H., Kitabayashi I.
EMBO J. 25:3955-3965(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HIPK2, PHOSPHORYLATION AT SER-249 AND SER-276 BY HIPK2, MUTAGENESIS OF SER-249 AND SER-276.
[11]"Crystallization and preliminary X-ray analyses of quaternary, ternary and binary protein-DNA complexes with involvement of AML1/Runx-1/CBFalpha Runt domain, CBFbeta and the C/EBPbeta bZip region."
Tahirov T.H., Inoue-Bungo T., Sasaki M., Shiina M., Kimura K., Sato K., Kumasaka T., Yamamoto M., Kamiya N., Ogata K.
Acta Crystallogr. D 57:850-853(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 62-177 IN COMPLEX WITH CEBPB; CBFB AND DNA.
[12]"Structural analyses of DNA recognition by the AML1/Runx-1 Runt domain and its allosteric control by CBFbeta."
Tahirov T.H., Inoue-Bungo T., Morii H., Fujikawa A., Sasaki M., Kimura K., Shiina M., Sato K., Kumasaka T., Yamamoto M., Ishii S., Ogata K.
Cell 104:755-767(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.65 ANGSTROMS) OF 60-182 IN COMPLEX WITH CEBPB; CBFB AND DNA, MUTAGENESIS OF ARG-80; ASN-109; TYR-113; ARG-142; LYS-144; THR-149; VAL-170; ASP-171; ARG-174 AND ARG-177.
[13]"The RUNX1 Runt domain at 1.25A resolution: a structural switch and specifically bound chloride ions modulate DNA binding."
Baeckstroem S., Wolf-Watz M., Grundstroem C., Haerd T., Grundstroem T., Sauer U.H.
J. Mol. Biol. 322:259-272(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) OF 60-173.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
D26532 mRNA. Translation: BAA05535.1.
D13802 mRNA. Translation: BAA02960.1.
X97306 mRNA. Translation: CAA65976.1.
AB046930 mRNA. Translation: BAB08105.1.
AF345649 mRNA. Translation: AAK29784.1.
AF193030 Genomic DNA. Translation: AAG32957.1.
PIRA56017.
UniGeneMm.4081.
Mm.470227.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1EANX-ray1.70A46-185[»]
1EAOX-ray1.40A/B46-185[»]
1EAQX-ray1.25A/B46-185[»]
1HJBX-ray3.00C/F60-182[»]
1HJCX-ray2.65A/D60-182[»]
1IO4X-ray3.00C60-182[»]
2J6WX-ray2.60A/B46-185[»]
ProteinModelPortalQ03347.
SMRQ03347. Positions 60-173, 319-345.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid198519. 37 interactions.
DIPDIP-40723N.
IntActQ03347. 3 interactions.
MINTMINT-91306.

PTM databases

PhosphoSiteQ03347.

Proteomic databases

PaxDbQ03347.
PRIDEQ03347.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

KEGGmmu:12394.

Organism-specific databases

CTD861.
MGIMGI:99852. Runx1.

Phylogenomic databases

eggNOGNOG123889.
HOGENOMHOG000045616.
HOVERGENHBG060268.
InParanoidQ03347.
KOK08367.
PhylomeDBQ03347.

Gene expression databases

CleanExMM_RUNX1.
GenevestigatorQ03347.

Family and domain databases

Gene3D2.60.40.720. 1 hit.
4.10.770.10. 1 hit.
InterProIPR000040. 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.
[Graphical view]
PANTHERPTHR11950. PTHR11950. 1 hit.
PfamPF00853. Runt. 1 hit.
PF08504. RunxI. 1 hit.
[Graphical view]
PIRSFPIRSF009374. TF_Runt-rel_RUNX. 1 hit.
PRINTSPR00967. ONCOGENEAML1.
SUPFAMSSF49417. SSF49417. 1 hit.
PROSITEPS51062. RUNT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ03347.
NextBio281140.
PROQ03347.
SOURCESearch...

Entry information

Entry nameRUNX1_MOUSE
AccessionPrimary (citable) accession number: Q03347
Secondary accession number(s): O08598 expand/collapse secondary AC list , Q62049, Q9ESB9, Q9ET65
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: November 1, 1996
Last modified: April 16, 2014
This is version 142 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MGD cross-references

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