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Reviewed, UniProtKB/Swiss-Prot Q01196 (RUNX1_HUMAN)

Last modified November 25, 2008. Version 115. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

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Names and origin

Protein namesRecommended name:
    Runt-related transcription factor 1
Alternative name(s):
    Core-binding factor subunit alpha-2
      Short name=CBF-alpha-2
    Acute myeloid leukemia 1 protein
    Oncogene AML-1
    Polyomavirus enhancer-binding protein 2 alpha B subunit
      Short name=PEBP2-alpha B
      Short name=PEA2-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
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length453 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

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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. The alpha subunit binds DNA and appears to have a role in the development of normal hematopoiesis. Isoform AML-1L interferes with the transactivation activity of RUNX1. Acts synergistically with ELF4 to transactivate the IL-3 promoter and with ELF2 to transactivate the mouse BLK promoter. Inhibits MYST4-dependent transcriptional activation.

Subunit structure

Heterodimer with CBFB. RUNX1 binds DNA as a monomer and through the Runt domain. DNA-binding is increased by heterodimerization. Isoform AML-1L can neither bind DNA nor heterodimerize. Interacts with TLE1 and THOC4. Interacts with 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 MYST3 and MYST4. Interacts with SUV39H1, leading to abrogate the transactivating and DNA-binding properties of RUNX1.

Subcellular location

Nucleus.

Tissue specificity

Expressed in all tissues examined except brain and heart. Highest levels in thymus, bone marrow and peripheral blood.

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 MYST3.

Methylated.

Involvement in disease

A chromosomal aberration involving RUNX1/AML1 is a cause of M2 type acute myeloid leukemia (AML-M2). Translocation t(8;21)(q22;q22) with RUNX1T1/MTG8/ETO.

A chromosomal aberration involving RUNX1/AML1 is a cause of therapy-related myelodysplastic syndrome (T-MDS). Translocation t(3;21)(q26;q22) with EAP, MSD1 or EVI1.

A chromosomal aberration involving RUNX1/AML1 is a cause of chronic myelogenous leukemia (CML). Translocation t(3;21)(q26;q22) with EAP, MSD1 or EVI1.

A chromosomal aberration involving RUNX1/AML1 is found in childhood acute lymphoblastic leukemia (ALL). Translocation t(12;21)(p13;q22) with TEL. The translocation fuses the 3'-end of TEL to the alternate 5'-exon of AML-1H.

Defects in RUNX1 are the cause of familial platelet disorder with associated myeloid malignancy (FPDMM) [MIM:601399]. FPDMM is an autosomal dominant disease characterized by qualitative and quantitative platelet defects, and propensity to develop acute myelogenous leukemia.

A chromosomal aberration involving RUNX1/AML1 is found in therapy-related myeloid malignancies. Translocation t(16;21)(q24;q22) that forms a RUNX1-CBFA2T3 fusion protein.

Sequence similarities

Contains 1 Runt domain.

Caution

The fusion of AML1 with EAP in T-MDS induces a change of reading frame in the latter resulting in 17 AA unrelated to those of EAP.

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Alternative products

This entry describes 11 isoforms produced by alternative splicing. [Align] [Select]

Notes: Additional isoforms seem to exist.
Isoform AML-1B (identifier: Q01196-1)

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 AML-1A (identifier: Q01196-2)

The sequence of this isoform differs from the canonical sequence as follows:
     440-453: APSARLEEAVWRPY → GGASCSRQARRDPGPWARTPSWGRGRPTDRISL
Isoform AML-1C (identifier: Q01196-3)

The sequence of this isoform differs from the canonical sequence as follows:
     242-250: DTRQIQPSP → EEDTAPWRC
     251-453: Missing.
Isoform AML-1E (identifier: Q01196-4)

The sequence of this isoform differs from the canonical sequence as follows:
     258-453: Missing.
Isoform AML-1FA (identifier: Q01196-5)

The sequence of this isoform differs from the canonical sequence as follows:
     178-224: RHRQKLDDQT...HPAPTPNPRA → SKCIHLGLVH...GWQAPVKPKS
     225-453: Missing.
Isoform AML-1FB (identifier: Q01196-6)

The sequence of this isoform differs from the canonical sequence as follows:
     178-188: RHRQKLDDQTK → NSLTWPRYPHI
     189-453: Missing.
Isoform AML-1FC (identifier: Q01196-7)

The sequence of this isoform differs from the canonical sequence as follows:
     137-242: VGRSGRGKSF...NPQPQSQMQD → VDGPREPRRH...SPSVHPATPI
     243-453: Missing.
Isoform AML-1G (identifier: Q01196-8)

The sequence of this isoform differs from the canonical sequence as follows:
     1-5: MRIPV → MASDSIFESFPSYPQCFMRECILGMNPSRDVH
Isoform AML-1H (identifier: Q01196-9)

The sequence of this isoform differs from the canonical sequence as follows:
     1-5: MRIPV → MNPSRDVH
Isoform AML-1I (identifier: Q01196-10)

The sequence of this isoform differs from the canonical sequence as follows:
     1-5: MRIPV → MPAAPRGPAQGEAAARTRSR
Isoform AML-1L (identifier: Q01196-11)

Also known as: AML1-delta N;

The sequence of this isoform differs from the canonical sequence as follows:
     1-105: Missing.

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Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 453453Runt-related transcription factor 1
PRO_0000174655

Regions

Domain50 – 178129Runt
Region80 – 845Interaction with DNA
Region135 – 1439Interaction with DNA
Region168 – 17710Interaction with DNA
Region291 – 37181Interaction with MYST3
Region307 – 40094Interaction with MYST4 By similarity
Compositional bias187 – 453267Pro/Ser/Thr-rich

Sites

Binding site1121Chloride 1
Binding site1161Chloride 1; via amide nitrogen
Binding site1391Chloride 2
Binding site1701Chloride 2; via amide nitrogen
Site177 – 1782Breakpoint for translocation to form AML1-EMV-1 (or AML1-EAP) in CML and T-MDS, to form AML1-MTG8 (ETO) in AML-M2 and to form AML1-CBFA2T3 in therapy-related myeloid malignancies
Site241 – 2422Breakpoint for translocation to form AML1-EAP in T-MDS and in CML

Amino acid modifications

Modified residue141Phosphothreonine
Modified residue211Phosphoserine

Natural variations

Alternative sequence1 – 105105Missing in isoform AML-1L.
VSP_005919
Alternative sequence1 – 55MRIPV → MASDSIFESFPSYPQCFMRE CILGMNPSRDVH in isoform AML-1G.
VSP_005917
Alternative sequence1 – 55MRIPV → MNPSRDVH in isoform AML-1H.
VSP_005916
Alternative sequence1 – 55MRIPV → MPAAPRGPAQGEAAARTRSR in isoform AML-1I.
VSP_005918
Alternative sequence137 – 242106VGRSG…SQMQD → VDGPREPRRHRQKLDDQTKP GSLSFSERLSELEQLRRTAM RVSPHHPAPTPNPRASLNHS TAFNPQPQSQMQDTRQIQPS PPWSYDQSYQYLGSIASPSV HPATPI in isoform AML-1FC.
VSP_005920
Alternative sequence178 – 22447RHRQK…PNPRA → SKCIHLGLVHPPGWYTLQAG ILRDHVSDSLGSTFPPGGWQ APVKPKS in isoform AML-1FA.
VSP_005923
Alternative sequence178 – 18811RHRQKLDDQTK → NSLTWPRYPHI in isoform AML-1FB.
VSP_005921
Alternative sequence189 – 453265Missing in isoform AML-1FB.
VSP_005922
Alternative sequence225 – 453229Missing in isoform AML-1FA.
VSP_005924
Alternative sequence242 – 2509DTRQIQPSP → EEDTAPWRC in isoform AML-1C.
VSP_005926
Alternative sequence243 – 453211Missing in isoform AML-1FC.
VSP_005925
Alternative sequence251 – 453203Missing in isoform AML-1C.
VSP_005927
Alternative sequence258 – 453196Missing in isoform AML-1E.
VSP_005928
Alternative sequence440 – 45314APSAR…VWRPY → GGASCSRQARRDPGPWARTP SWGRGRPTDRISL in isoform AML-1A.
VSP_005929
Natural variant1391R → Q in FPDMM.
VAR_012128
Natural variant1741R → Q in FPDMM.
VAR_012129
Natural variant4311S → R: dbSNP rs1055308.
VAR_013177
Natural variant4331S → R: dbSNP rs1055309.
VAR_013178

Experimental info

Mutagenesis801R → A: Strongly reduces DNA-binding
Mutagenesis831K → A: Strongly reduces DNA-binding
Mutagenesis841T → A: No effect on DNA binding
Mutagenesis1071A → T: Loss of heterodimerization
Mutagenesis1081G → R: Loss of heterodimerization
Mutagenesis1351R → A: Strongly reduces DNA-binding
Mutagenesis1391R → A: Strongly reduces DNA-binding
Mutagenesis1421R → A: Strongly reduces DNA-binding
Mutagenesis145 – 453309Missing: No DNA-binding
Mutagenesis1671K → A: Reduces DNA-binding
Mutagenesis1691T → A: Strongly reduces DNA-binding
Mutagenesis1711D → A: Strongly reduces DNA-binding
Mutagenesis1741R → A: Strongly reduces DNA-binding
Mutagenesis1771R → A: Strongly reduces DNA-binding
Sequence conflict4121S → F in AAA51720. Ref.1

Secondary structure

1 ....................... 453
Helix Strand Turn

Details...

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Sequences

Sequence LengthMass (Da)Tools
Isoform AML-1B [UniParc].

Last modified November 25, 2008. Version 3.
Checksum: 4F1F193A7CADDBAB

FASTA45348,737
        10         20         30         40         50         60 
MRIPVDASTS RRFTPPSTAL SPGKMSEALP LGAPDAGAAL AGKLRSGDRS 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 
QDTRQIQPSP PWSYDQSYQY LGSIASPSVH PATPISPGRA SGMTTLSAEL SSRLSTAPDL 

       310        320        330        340        350        360 
TAFSDPRQFP ALPSISDPRM HYPGAFTYSP TPVTSGIGIG MSAMGSATRY HTYLPPPYPG 

       370        380        390        400        410        420 
SSQAQGGPFQ ASSPSYHLYY GASAGSYQFS MVGGERSPPR ILPPCTNAST GSALLNPSLP 

       430        440        450 
NQSDVVEAEG SHSNSPTNMA PSARLEEAVW RPY

« Hide

Isoform AML-1A [UniParc].

Checksum: 13349A060DC3B793
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47250,701
Isoform AML-1C [UniParc].

Checksum: FADB4980D9FCA9D5
Show »

25027,427
Isoform AML-1E [UniParc].

Checksum: 10A5E857CB432487
Show »

25728,226
Isoform AML-1FA [UniParc].

Checksum: 08A3748CC9F566E5
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22424,049
Isoform AML-1FB [UniParc].

Checksum: D2B706A902D72B2A
Show »

18820,395