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Protein

Runt-related transcription factor 2

Gene

Runx2

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

Functioni

Transcription factor involved in osteoblastic differentiation and skeletal morphogenesis. Essential for the maturation of osteoblasts and both intramembranous and endochondral ossification. 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, osteocalcin, osteopontin, bone sialoprotein, alpha 1(I) collagen, LCK, IL-3 and GM-CSF promoters. Inhibits KAT6B-dependent transcriptional activation (By similarity). In osteoblasts, supports transcription activation: synergizes with SPEN/MINT to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE).By similarity2 Publications

GO - Molecular functioni

  • ATP binding Source: InterPro
  • bHLH transcription factor binding Source: MGI
  • chromatin binding Source: MGI
  • DNA binding Source: MGI
  • DNA binding transcription factor activity Source: MGI
  • protein domain specific binding Source: MGI
  • repressing transcription factor binding Source: MGI
  • RNA polymerase II proximal promoter sequence-specific DNA binding Source: NTNU_SB
  • transcriptional activator activity, RNA polymerase II proximal promoter sequence-specific DNA binding Source: NTNU_SB
  • transcription regulatory region DNA binding Source: UniProtKB

GO - Biological processi

  • BMP signaling pathway Source: BHF-UCL
  • cell maturation Source: MGI
  • cellular response to BMP stimulus Source: BHF-UCL
  • chondrocyte development Source: MGI
  • chondrocyte differentiation Source: MGI
  • embryonic cranial skeleton morphogenesis Source: MGI
  • embryonic forelimb morphogenesis Source: MGI
  • endochondral ossification Source: MGI
  • negative regulation of smoothened signaling pathway Source: MGI
  • negative regulation of transcription, DNA-templated Source: UniProtKB
  • neuron differentiation Source: GO_Central
  • odontogenesis of dentin-containing tooth Source: MGI
  • osteoblast development Source: MGI
  • osteoblast differentiation Source: MGI
  • osteoblast fate commitment Source: MGI
  • positive regulation of cell proliferation Source: MGI
  • positive regulation of chondrocyte differentiation Source: MGI
  • positive regulation of gene expression Source: MGI
  • positive regulation of osteoblast differentiation Source: MGI
  • positive regulation of transcription, DNA-templated Source: MGI
  • positive regulation of transcription by RNA polymerase II Source: NTNU_SB
  • positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus Source: BHF-UCL
  • regulation of fibroblast growth factor receptor signaling pathway Source: MGI
  • regulation of odontogenesis of dentin-containing tooth Source: MGI
  • regulation of ossification Source: MGI
  • regulation of osteoblast differentiation Source: MGI
  • skeletal system development Source: MGI
  • skeletal system morphogenesis Source: MGI
  • stem cell differentiation Source: MGI
  • T cell differentiation Source: MGI

Keywordsi

Molecular functionDNA-binding
Biological processDifferentiation, Transcription, Transcription regulation

Enzyme and pathway databases

ReactomeiR-MMU-8878166 Transcriptional regulation by RUNX2
R-MMU-8939902 Regulation of RUNX2 expression and activity
R-MMU-8940973 RUNX2 regulates osteoblast differentiation
R-MMU-8941326 RUNX2 regulates bone development

Names & Taxonomyi

Protein namesi
Recommended name:
Runt-related transcription factor 2
Alternative name(s):
Acute myeloid leukemia 3 protein
Core-binding factor subunit alpha-1
Short name:
CBF-alpha-1
Oncogene AML-3
Osteoblast-specific transcription factor 2
Short name:
OSF-2
Polyomavirus enhancer-binding protein 2 alpha A subunit
Short name:
PEA2-alpha A
Short name:
PEBP2-alpha A
SL3-3 enhancer factor 1 alpha A subunit
SL3/AKV core-binding factor alpha A subunit
Gene namesi
Name:Runx2
Synonyms:Aml3, Cbfa1, Osf2, Pebp2a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 17

Organism-specific databases

MGIiMGI:99829 Runx2

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

Nucleus

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL1681609

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001746601 – 607Runt-related transcription factor 2Add BLAST607

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki324Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)By similarity
Modified residuei353Asymmetric dimethylarginineCombined sources1
Modified residuei537Phosphoserine; by CDK1By similarity1

Post-translational modificationi

Phosphorylated; probably by MAP kinases (MAPK). Phosphorylation by HIPK3 is required for the SPEN/MINT and FGF2 transactivation during osteoblastic differentiation. Phosphorylation at Ser-537 by CDK1 promotes endothelial cell proliferation required for tumor angiogenesis probably by facilitating cell cycle progression (By similarity).By similarity

Keywords - PTMi

Isopeptide bond, Methylation, Phosphoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ08775
PaxDbiQ08775
PeptideAtlasiQ08775
PRIDEiQ08775

PTM databases

iPTMnetiQ08775
PhosphoSitePlusiQ08775

Expressioni

Tissue specificityi

Found in thymus and testis, T-cell lines but not in B-cell lines. Isoform 2 is exclusively found in bone, particularly in osteoblasts; isoforms 3 and 4 are expressed in T-cell lines; isoforms 5, 6, 7, 8 and 9 can be found in osteoblasts and osteosarcoma cell lines.

Developmental stagei

Expression occurs early during skeletal development and is restricted to cells of the mesenchymal condensations and of the osteoblast lineage. Expression of isoform 2 in the embryo reaches a peak at 12.5 dpc.

Gene expression databases

BgeeiENSMUSG00000039153
CleanExiMM_RUNX2
ExpressionAtlasiQ08775 baseline and differential
GenevisibleiQ08775 MM

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 XRCC6 (Ku70) and XRCC5 (Ku80). Interacts with CCNB1, KAT6A and KAT6B (By similarity). Interacts with HIVEP3. Interacts with IFI204. Interaction with SATB2; the interaction results in enhanced DNA binding and transactivation by these transcription factors. Binds to HIPK3. Interacts (isoform 3) with DDX5. Interacts with FOXO1 (via a C-terminal region); the interaction inhibits RUNX2 transcriptional activity towards BGLAP. Interacts with FOXP3 (By similarity). Interacts with TMEM119 (PubMed:21239498). Interacts with OLFM2 (By similarity).By similarity7 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • bHLH transcription factor binding Source: MGI
  • protein domain specific binding Source: MGI
  • repressing transcription factor binding Source: MGI

Protein-protein interaction databases

BioGridi198518, 22 interactors
CORUMiQ08775
DIPiDIP-36316N
ELMiQ08775
IntActiQ08775, 13 interactors
MINTiQ08775
STRINGi10090.ENSMUSP00000109201

Structurei

3D structure databases

ProteinModelPortaliQ08775
SMRiQ08775
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini187 – 315RuntPROSITE-ProRule annotationAdd BLAST129

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 88Interaction with IFI2041 PublicationAdd BLAST88
Regioni242 – 258Required for interaction with FOXO11 PublicationAdd BLAST17
Regioni422 – 525Interaction with KAT6ABy similarityAdd BLAST104
Regioni460 – 554Interaction with KAT6BBy similarityAdd BLAST95

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi128 – 156Poly-GlnAdd BLAST29
Compositional biasi158 – 175Poly-AlaAdd BLAST18
Compositional biasi323 – 607Pro/Ser/Thr-richAdd BLAST285

Domaini

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

Phylogenomic databases

eggNOGiKOG3982 Eukaryota
ENOG4111J4Y LUCA
GeneTreeiENSGT00390000016964
HOVERGENiHBG060268
InParanoidiQ08775
KOiK09278
OMAiSDPRQFT
OrthoDBiEOG091G0CXB
PhylomeDBiQ08775

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_sf
IPR013524 Runt_dom
IPR027384 Runx_central_dom_sf
IPR013711 RunxI_C_dom
PANTHERiPTHR11950 PTHR11950, 2 hits
PfamiView protein in Pfam
PF00853 Runt, 1 hit
PF08504 RunxI, 1 hit
PRINTSiPR00967 ONCOGENEAML1
SUPFAMiSSF49417 SSF49417, 1 hit
PROSITEiView protein in PROSITE
PS51062 RUNT, 1 hit

Sequences (9)i

Sequence statusi: Complete.

This entry describes 9 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q08775-1) [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
MLHSPHKQPQ NHKCGANFLQ EDCKKALAFK WLISAGHYQP PRPTESVSAL
60 70 80 90 100
TTVHAGIFKA ASSIYNRGHK FYLEKKGGTM ASNSLFSAVT PCQQSFFWDP
110 120 130 140 150
STSRRFSPPS SSLQPGKMSD VSPVVAAQQQ QQQQQQQQQQ QQQQQQQQQQ
160 170 180 190 200
QQQQQQEAAA AAAAAAAAAA AAAAAVPRLR PPHDNRTMVE IIADHPAELV
210 220 230 240 250
RTDSPNFLCS VLPSHWRCNK TLPVAFKVVA LGEVPDGTVV TVMAGNDENY
260 270 280 290 300
SAELRNASAV MKNQVARFND LRFVGRSGRG KSFTLTITVF TNPPQVATYH
310 320 330 340 350
RAIKVTVDGP REPRRHRQKL DDSKPSLFSD RLSDLGRIPH PSMRVGVPPQ
360 370 380 390 400
NPRPSLNSAP SPFNPQGQSQ ITDPRQAQSS PPWSYDQSYP SYLSQMTSPS
410 420 430 440 450
IHSTTPLSST RGTGLPAITD VPRRISDDDT ATSDFCLWPS SLSKKSQAGA
460 470 480 490 500
SELGPFSDPR QFPSISSLTE SRFSNPRMHY PATFTYTPPV TSGMSLGMSA
510 520 530 540 550
TTHYHTYLPP PYPGSSQSQS GPFQTSSTPY LYYGTSSASY QFPMVPGGDR
560 570 580 590 600
SPSRMVPPCT TTSNGSTLLN PNLPNQNDGV DADGSHSSSP TVLNSSGRMD

ESVWRPY
Length:607
Mass (Da):66,205
Last modified:November 2, 2001 - v2
Checksum:iE87A4497ED19EE0E
GO
Isoform 2 (identifier: Q08775-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     47-57: Missing.

Show »
Length:596
Mass (Da):65,154
Checksum:i3365DB4F7F199BA0
GO
Isoform 3 (identifier: Q08775-3) [UniParc]FASTAAdd to basket
Also known as: PEBP2-alpha A1

The sequence of this isoform differs from the canonical sequence as follows:
     1-98: MLHSPHKQPQ...VTPCQQSFFW → MRIPV
     156-156: Missing.

Show »
Length:513
Mass (Da):55,752
Checksum:iEAF92506819B2D28
GO
Isoform 4 (identifier: Q08775-4) [UniParc]FASTAAdd to basket
Also known as: PEBP2-alpha A2

The sequence of this isoform differs from the canonical sequence as follows:
     1-98: MLHSPHKQPQ...VTPCQQSFFW → MRIPV
     156-156: Missing.
     399-400: PS → LS
     401-607: Missing.

Show »
Length:306
Mass (Da):33,599
Checksum:i0CF6BFF4B8CD4DBB
GO
Isoform 5 (identifier: Q08775-5) [UniParc]FASTAAdd to basket
Also known as: G1

The sequence of this isoform differs from the canonical sequence as follows:
     1-79: Missing.

Show »
Length:528
Mass (Da):57,417
Checksum:i1675D3EA1CB5D4EE
GO
Isoform 6 (identifier: Q08775-6) [UniParc]FASTAAdd to basket
Also known as: G2

The sequence of this isoform differs from the canonical sequence as follows:
     1-79: Missing.
     316-373: Missing.

Show »
Length:470
Mass (Da):51,032
Checksum:iE77D395B48886713
GO
Isoform 7 (identifier: Q08775-7) [UniParc]FASTAAdd to basket
Also known as: U1

The sequence of this isoform differs from the canonical sequence as follows:
     1-79: Missing.
     427-439: DDDTATSDFCLWP → GFCGTTTTTTTKL
     440-607: Missing.

Show »
Length:360
Mass (Da):39,277
Checksum:i38F2DE7E6AC8747C
GO
Isoform 8 (identifier: Q08775-8) [UniParc]FASTAAdd to basket
Also known as: Y1

The sequence of this isoform differs from the canonical sequence as follows:
     1-79: Missing.
     428-607: DDTATSDFCL...RMDESVWRPY → SEPSTLDSQS...QPVPEAPDAN

Show »
Length:548
Mass (Da):58,669
Checksum:iC05C800013B5A912
GO
Isoform 9 (identifier: Q08775-9) [UniParc]FASTAAdd to basket
Also known as: Y2

The sequence of this isoform differs from the canonical sequence as follows:
     1-79: Missing.
     316-373: Missing.
     428-607: DDTATSDFCL...RMDESVWRPY → SEPSTLDSQS...QPVPEAPDAN

Show »
Length:490
Mass (Da):52,285
Checksum:i86043D899DFA524F
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti266A → S in AAC78626 (PubMed:9651525).Curated1
Sequence conflicti280G → S in AAC78626 (PubMed:9651525).Curated1
Sequence conflicti373D → N in AAC78626 (PubMed:9651525).Curated1
Sequence conflicti375R → T in AAC78626 (PubMed:9651525).Curated1
Sequence conflicti396M → L in AAC78626 (PubMed:9651525).Curated1
Sequence conflicti459P → L in AAC78626 (PubMed:9651525).Curated1
Sequence conflicti472R → P in AAC78626 (PubMed:9651525).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0059401 – 98MLHSP…QSFFW → MRIPV in isoform 3 and isoform 4. 2 PublicationsAdd BLAST98
Alternative sequenceiVSP_0059391 – 79Missing in isoform 5, isoform 6, isoform 7, isoform 8 and isoform 9. 1 PublicationAdd BLAST79
Alternative sequenceiVSP_00594147 – 57Missing in isoform 2. 2 PublicationsAdd BLAST11
Alternative sequenceiVSP_005942156Missing in isoform 3 and isoform 4. 2 Publications1
Alternative sequenceiVSP_005943316 – 373Missing in isoform 6 and isoform 9. 1 PublicationAdd BLAST58
Alternative sequenceiVSP_005944399 – 400PS → LS in isoform 4. 2 Publications2
Alternative sequenceiVSP_005945401 – 607Missing in isoform 4. 2 PublicationsAdd BLAST207
Alternative sequenceiVSP_005946427 – 439DDDTA…FCLWP → GFCGTTTTTTTKL in isoform 7. 1 PublicationAdd BLAST13
Alternative sequenceiVSP_005947428 – 607DDTAT…VWRPY → SEPSTLDSQSSTTLFLSSEE PGPSTAALPSPSSSCEPQPF SPSPMLPPLLQPLSTASTVP APCVPRRTGLYTIVTSSPEA APHLVDWMPSCPTATSPGVR GKDHERPQTMMAPAPALASE RGHSQHAGPARDDHAEHPGT SPKPCAPPAAAATLEASVGD ILVELRTMNGHLDIIAKALT KLASSLVPQSQPVPEAPDAN in isoform 8 and isoform 9. 1 PublicationAdd BLAST180
Alternative sequenceiVSP_005948440 – 607Missing in isoform 7. 1 PublicationAdd BLAST168

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D14636 mRNA Translation: BAA03485.1
D14637 mRNA Translation: BAA03486.1
AF010284 mRNA Translation: AAB65409.1
AF005936 mRNA Translation: AAB82419.1
AF053948 Genomic DNA Translation: AAC77440.1
AF053951 mRNA Translation: AAC78623.1
AF053956 mRNA Translation: AAC78626.1
AF134836 Genomic DNA Translation: AAF22568.1
AF134836 Genomic DNA Translation: AAF22569.1
AB013129 Genomic DNA Translation: BAA85345.1
AB013129 Genomic DNA Translation: BAA85346.1
AH009404 Genomic DNA Translation: AAF73290.1
CCDSiCCDS37624.2 [Q08775-5]
PIRiA48233
RefSeqiNP_001139510.1, NM_001146038.2 [Q08775-5]
NP_001258556.1, NM_001271627.1 [Q08775-5]
NP_033950.2, NM_009820.5 [Q08775-5]
XP_006523607.1, XM_006523544.2 [Q08775-1]
XP_006523608.1, XM_006523545.2 [Q08775-2]
UniGeneiMm.391013
Mm.391017
Mm.491666

Genome annotation databases

EnsembliENSMUST00000113571; ENSMUSP00000109201; ENSMUSG00000039153 [Q08775-5]
ENSMUST00000159943; ENSMUSP00000124918; ENSMUSG00000039153 [Q08775-5]
ENSMUST00000160673; ENSMUSP00000123743; ENSMUSG00000039153 [Q08775-2]
GeneIDi12393
KEGGimmu:12393
UCSCiuc008cpy.3 mouse [Q08775-6]
uc008cqa.3 mouse [Q08775-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Entry informationi

Entry nameiRUNX2_MOUSE
AccessioniPrimary (citable) accession number: Q08775
Secondary accession number(s): O35183
, Q08776, Q9JLN0, Q9QUQ6, Q9QY29, Q9R0U4, Q9Z2J7
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 2, 2001
Last sequence update: November 2, 2001
Last modified: April 25, 2018
This is version 184 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health