Q13761 (RUNX3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	RUNX3
Synonyms:	AML2, CBFA3, PEBP2A3

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	415 AA.
Sequence status	Complete.
Protein existence	Evidence 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.
Subunit structure	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. Ref.8 Ref.9 Ref.11
Subcellular location	Nucleus. Cytoplasm. Note: The tyrosine phosphorylated form localizes to the cytoplasm. Ref.11
Domain	A proline/serine/threonine rich region at the C-terminus is necessary for transcriptional activation of target genes.
Post-translational modification	Phosphorylated on tyrosine residues by SRC. Phosphorylated by LCK and FYN. Ref.11
Sequence similarities	Contains 1 Runt domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Ligand	DNA-binding
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	axon guidance Inferred from electronic annotation. Source: Compara cell maturation Inferred from electronic annotation. Source: Compara hair follicle morphogenesis Inferred from electronic annotation. Source: Compara induction of apoptosis Inferred from sequence or structural similarity. Source: UniProtKB interferon-gamma production Inferred from electronic annotation. Source: Compara negative regulation of cell cycle Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of epithelial cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: BHF-UCL peripheral nervous system neuron development Traceable author statement PubMed 20096094. Source: BHF-UCL protein phosphorylation Inferred from direct assay Ref.11. Source: UniProtKB
Cellular_component	cytoplasm Inferred from direct assay Ref.11. Source: UniProtKB nuclear chromatin Inferred from sequence or structural similarity. Source: BHF-UCL
Molecular_function	ATP binding Non-traceable author statement Ref.2. Source: UniProtKB RNA polymerase II regulatory region sequence-specific DNA binding Inferred from sequence or structural similarity. Source: BHF-UCL sequence-specific DNA binding RNA polymerase II transcription factor activity Inferred from sequence or structural similarity. Source: BHF-UCL
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CTNNB1	P35222	12	EBI-925990,EBI-491549
TCF7L2	Q9NQB0	14	EBI-925990,EBI-924724
TLE1	Q04724	3	EBI-925990,EBI-711424

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q13761-1)

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: Q13761-2)

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

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 415	415	Runt-related transcription factor 3		PRO_0000174662
Regions
	Domain	54 – 182	129	Runt
	Compositional bias	23 – 27	5	Poly-Gly
	Compositional bias	191 – 415	225	Pro/Ser/Thr-rich
Amino acid modifications
	Modified residue	243	1	Phosphoserine Ref.10
Natural variations
	Alternative sequence	1 – 5	5	MRIPV → MASNSIFDSFPTYSPTFIR in isoform 2.		VSP_005949
Experimental info
	Sequence conflict	249	1	D → V in CAA56093. Ref.2
	Sequence conflict	253	1	P → S in CAA56093. Ref.2
	Sequence conflict	256	1	P → S in CAA56093. Ref.2
	Sequence conflict	259	1	T → S in CAA56093. Ref.2
	Sequence conflict	268 – 269	2	MH → IY in CAA56093. Ref.2
	Sequence conflict	271	1	P → T in CAA56093. Ref.2
	Sequence conflict	297 – 298	2	MP → IS in CAA56093. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1999. Version 2. Checksum: 593FBFB3C4639BBD	FASTA	415	44,356
	10 20 30 40 50 60 MRIPVDPSTS RRFTPPSPAF PCGGGGGKMG ENSGALSAQA AVGPGGRARP EVRSMVDVLA 70 80 90 100 110 120 DHAGELVRTD SPNFLCSVLP SHWRCNKTLP VAFKVVALGD VPDGTVVTVM AGNDENYSAE 130 140 150 160 170 180 LRNASAVMKN QVARFNDLRF VGRSGRGKSF TLTITVFTNP TQVATYHRAI KVTVDGPREP 190 200 210 220 230 240 RRHRQKLEDQ TKPFPDRFGD LERLRMRVTP STPSPRGSLS TTSHFSSQPQ TPIQGTSELN 250 260 270 280 290 300 PFSDPRQFDR SFPTLPTLTE SRFPDPRMHY PGAMSAAFPY SATPSGTSIS SLSVAGMPAT 310 320 330 340 350 360 SRFHHTYLPP PYPGAPQNQS GPFQANPSPY HLYYGTSSGS YQFSMVAGSS SGGDRSPTRM 370 380 390 400 410 LASCTSSAAS VAAGNLMNPS LGGQSDGVEA DGSHSNSPTA LSTPGRMDEA VWRPY
	Isoform 2 [UniParc]. Checksum: E9A43E96EDF82389	FASTA	429	45,922
	10 20 30 40 50 60 MASNSIFDSF PTYSPTFIRD PSTSRRFTPP SPAFPCGGGG GKMGENSGAL SAQAAVGPGG 70 80 90 100 110 120 RARPEVRSMV DVLADHAGEL VRTDSPNFLC SVLPSHWRCN KTLPVAFKVV ALGDVPDGTV 130 140 150 160 170 180 VTVMAGNDEN YSAELRNASA VMKNQVARFN DLRFVGRSGR GKSFTLTITV FTNPTQVATY 190 200 210 220 230 240 HRAIKVTVDG PREPRRHRQK LEDQTKPFPD RFGDLERLRM RVTPSTPSPR GSLSTTSHFS 250 260 270 280 290 300 SQPQTPIQGT SELNPFSDPR QFDRSFPTLP TLTESRFPDP RMHYPGAMSA AFPYSATPSG 310 320 330 340 350 360 TSISSLSVAG MPATSRFHHT YLPPPYPGAP QNQSGPFQAN PSPYHLYYGT SSGSYQFSMV 370 380 390 400 410 420 AGSSSGGDRS PTRMLASCTS SAASVAAGNL MNPSLGGQSD GVEADGSHSN SPTALSTPGR MDEAVWRPY

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Cloning, mapping and expression of PEBP2 alpha C, a third gene encoding the mammalian Runt domain." Bae S.-C., Takahashi E., Zhang Y.-W., Ogawa E., Shigesada K., Namba Y., Satake M., Ito Y. Gene 159:245-248(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"AML1, AML2, and AML3, the human members of the runt domain gene-family: cDNA structure, expression, and chromosomal localization." Levanon D., Negreanu V., Bernstein Y., Bar-Am I., Avivi L., Groner Y. Genomics 23:425-432(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[3]	Groner Y. Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). Tissue: Skin.
[7]	"Identification of a new murine runt domain-containing gene, Cbfa3, and localization of the human homolog, CBFA3, to chromosome 1p35-pter." Wijmenga C., Speck N.A., Dracopoli N.C., Hofker M.H., Liu P., Collins F.S. Genomics 26:611-614(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 95-148.
[8]	"Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors." Levanon D., Goldstein R.E., Bernstein Y., Tang H., Goldenberg D., Stifani S., Paroush Z., Groner Y. Proc. Natl. Acad. Sci. U.S.A. 95:11590-11595(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH TLE1.
[9]	"RUNX1 associates with histone deacetylases and SUV39H1 to repress transcription." Reed-Inderbitzin E., Moreno-Miralles I., Vanden-Eynden S.K., Xie J., Lutterbach B., Durst-Goodwin K.L., Luce K.S., Irvin B.J., Cleary M.L., Brandt S.J., Hiebert S.W. Oncogene 25:5777-5786(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH SUV39H1.
[10]	"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis." Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-243, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[11]	"Src kinase phosphorylates RUNX3 at tyrosine residues and localizes the protein in the cytoplasm." Goh Y.M., Cinghu S., Hong E.T., Lee Y.S., Kim J.H., Jang J.W., Li Y.H., Chi X.Z., Lee K.S., Wee H., Ito Y., Oh B.C., Bae S.C. J. Biol. Chem. 285:10122-10129(2010) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, PHOSPHORYLATION, INTERACTION WITH SRC; FYN AND LCK.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	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.
IPI	IPI00004015. IPI00218386.
PIR	B55563. S60078.
RefSeq	NP_001026850.1. NM_001031680.2. NP_004341.1. NM_004350.2.
UniGene	Hs.170019.
3D structure databases
ProteinModelPortal	Q13761.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q13761. 9 interactions.
STRING	9606.ENSP00000343477.
PTM databases
PhosphoSite	Q13761.
Polymorphism databases
DMDM	17368453.
Proteomic databases
PaxDb	Q13761.
PRIDE	Q13761.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000308873; ENSP00000308051; ENSG00000020633. ENST00000338888; ENSP00000343477; ENSG00000020633. ENST00000399916; ENSP00000382800; ENSG00000020633.
GeneID	864.
KEGG	hsa:864.
UCSC	uc001bjq.3. human.
Organism-specific databases
CTD	864.
GeneCards	GC01M025226.
HGNC	HGNC:10473. RUNX3.
HPA	CAB025416.
MIM	600210. gene.
neXtProt	NX_Q13761.
PharmGKB	PA34886.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG123889.
HOGENOM	HOG000045616.
HOVERGEN	HBG060268.
KO	K09279.
OMA	FPYSATP.
OrthoDB	EOG47M1XZ.
Enzyme and pathway databases
Pathway_Interaction_DB	smad2_3nuclearpathway. Regulation of nuclear SMAD2/3 signaling.
Gene expression databases
ArrayExpress	Q13761.
Bgee	Q13761.
CleanEx	HS_RUNX3.
Genevestigator	Q13761.
GermOnline	ENSG00000020633. Homo sapiens.
Family and domain databases
Gene3D	2.60.40.720. 1 hit.
InterPro	IPR000040. AML1_Runt. IPR008967. p53-like_TF_DNA-bd. IPR012346. p53/RUNT-type_TF_DNA-bd. IPR013524. Runt_dom. IPR013711. RunxI_c_dom. IPR016554. TF_Runt-rel_RUNX. [Graphical view]
PANTHER	PTHR11950. PTHR11950. 1 hit.
Pfam	PF00853. Runt. 1 hit. PF08504. RunxI. 1 hit. [Graphical view]
PIRSF	PIRSF009374. TF_Runt-rel_RUNX. 1 hit.
PRINTS	PR00967. ONCOGENEAML1.
SUPFAM	SSF49417. P53_like_DNA_bnd. 1 hit.
PROSITE	PS51062. RUNT. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	864.
NextBio	3602.
SOURCE	Search...

Entry information

Entry name

RUNX3_HUMAN

Accession

Primary (citable) accession number: Q13761
Secondary accession number(s): B1AJV5, Q12969, Q13760

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 2, 2001
Last sequence update:	November 1, 1999
Last modified:	May 1, 2013
This is version 137 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.