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Q13950

- RUNX2_HUMAN

UniProt

Q13950 - RUNX2_HUMAN

Protein

Runt-related transcription factor 2

Gene

RUNX2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 151 (01 Oct 2014)
      Sequence version 2 (02 Nov 2001)
      Previous versions | rss
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    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. In osteoblasts, supports transcription activation: synergizes with SPEN/MINT to enhance FGFR2-mediated activation of the osteocalcin FGF-responsive element (OCFRE) By similarity. Inhibits KAT6B-dependent transcriptional activation.By similarity1 Publication

    GO - Molecular functioni

    1. ATP binding Source: InterPro
    2. chromatin binding Source: Ensembl
    3. protein binding Source: UniProtKB
    4. RNA polymerase II core promoter proximal region sequence-specific DNA binding Source: Ensembl
    5. RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in positive regulation of transcription Source: Ensembl
    6. sequence-specific DNA binding transcription factor activity Source: ProtInc

    GO - Biological processi

    1. BMP signaling pathway Source: BHF-UCL
    2. cell maturation Source: Ensembl
    3. cellular response to BMP stimulus Source: BHF-UCL
    4. chondrocyte development Source: Ensembl
    5. embryonic cranial skeleton morphogenesis Source: Ensembl
    6. embryonic forelimb morphogenesis Source: Ensembl
    7. endochondral ossification Source: Ensembl
    8. gene expression Source: Reactome
    9. negative regulation of smoothened signaling pathway Source: Ensembl
    10. negative regulation of transcription, DNA-templated Source: UniProtKB
    11. odontogenesis of dentin-containing tooth Source: Ensembl
    12. ossification Source: UniProtKB
    13. osteoblast development Source: Ensembl
    14. osteoblast differentiation Source: UniProtKB
    15. osteoblast fate commitment Source: Ensembl
    16. positive regulation of cell proliferation Source: Ensembl
    17. positive regulation of chondrocyte differentiation Source: Ensembl
    18. positive regulation of osteoblast differentiation Source: Ensembl
    19. positive regulation of transcription, DNA-templated Source: UniProtKB
    20. positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus Source: BHF-UCL
    21. regulation of fibroblast growth factor receptor signaling pathway Source: Ensembl
    22. regulation of odontogenesis of dentin-containing tooth Source: Ensembl
    23. stem cell differentiation Source: Ensembl
    24. T cell differentiation Source: Ensembl
    25. transcription initiation from RNA polymerase II promoter Source: Reactome

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    DNA-binding

    Enzyme and pathway databases

    ReactomeiREACT_118713. YAP1- and WWTR1 (TAZ)-stimulated gene expression.
    SignaLinkiQ13950.

    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
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 6

    Organism-specific databases

    HGNCiHGNC:10472. RUNX2.

    Subcellular locationi

    GO - Cellular componenti

    1. cytoplasm Source: Ensembl
    2. nuclear chromatin Source: BHF-UCL
    3. nucleus Source: HPA
    4. transcription factor complex Source: Ensembl

    Keywords - Cellular componenti

    Nucleus

    Pathology & Biotechi

    Involvement in diseasei

    Cleidocranial dysplasia (CLCD) [MIM:119600]: Autosomal dominant skeletal disorder with high penetrance and variable expressivity. It is due to defective endochondral and intramembranous bone formation. Typical features include hypoplasia/aplasia of clavicles, patent fontanelles, wormian bones (additional cranial plates caused by abnormal ossification of the calvaria), supernumerary teeth, short stature, and other skeletal changes. In some cases defects in RUNX2 are exclusively associated with dental anomalies.14 Publications
    Note: The disease is caused by mutations affecting the gene represented in this entry.
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti53 – 531Q → L in CLCD. 1 Publication
    VAR_064081
    Natural varianti84 – 841A → AAAAAAAAAAA in CLCD associated with brachydactyly of hands and feet. 1 Publication
    VAR_012130
    Natural varianti113 – 1131L → R in CLCD. 1 Publication
    VAR_012132
    Natural varianti118 – 1181S → N in CLCD. 1 Publication
    VAR_064082
    Natural varianti118 – 1181S → R in CLCD. 1 Publication
    VAR_012133
    Natural varianti121 – 1211F → C in CLCD. 1 Publication
    VAR_012134
    Natural varianti123 – 1231C → R in CLCD. 1 Publication
    VAR_012135
    Natural varianti131 – 1311R → C in CLCD. 1 Publication
    VAR_064083
    Natural varianti131 – 1311R → G in CLCD. 1 Publication
    VAR_064084
    Natural varianti131 – 1311R → S in CLCD. 1 Publication
    VAR_064085
    Natural varianti133 – 1331Missing in CLCD. 1 Publication
    VAR_012136
    Natural varianti136 – 1361L → P in CLCD. 1 Publication
    VAR_064086
    Natural varianti156 – 1561V → D in CLCD. 1 Publication
    VAR_064087
    Natural varianti156 – 1561V → G in CLCD. 1 Publication
    VAR_064088
    Natural varianti169 – 1691R → P in CLCD. 2 Publications
    VAR_064089
    Natural varianti169 – 1691R → Q in CLCD. 1 Publication
    VAR_012137
    Natural varianti175 – 1751M → K in CLCD. 1 Publication
    VAR_064090
    Natural varianti175 – 1751M → R in CLCD; abolishes DNA binding. 2 Publications
    VAR_012138
    Natural varianti175 – 1751M → V in CLCD. 1 Publication
    VAR_064091
    Natural varianti187 – 1871F → S in CLCD. 1 Publication
    VAR_064092
    Natural varianti190 – 1901R → Q in CLCD; abolishes DNA binding. 1 Publication
    VAR_012139
    Natural varianti190 – 1901R → W in CLCD; has severely impaired DNA binding and transactivation. 3 Publications
    VAR_012140
    Natural varianti191 – 1911S → N in CLCD; abolishes DNA binding. 2 Publications
    VAR_012141
    Natural varianti193 – 1931R → C in CLCD. 1 Publication
    VAR_012142
    Natural varianti193 – 1931R → Q in CLCD. 1 Publication
    VAR_064093
    Natural varianti197 – 1971F → S in CLCD; retains heterodimerization activity together with a trace potential for DNA binding; retains a low but still substantial transactivation activity. 2 Publications
    VAR_012143
    Natural varianti199 – 1991L → F in CLCD; abolishes DNA binding. 1 Publication
    VAR_012144
    Natural varianti200 – 2001T → A in CLCD; mild; associated also with isolated dental anomalies; normal DNA binding. 1 Publication
    VAR_012145
    Natural varianti200 – 2001T → I in CLCD. 1 Publication
    VAR_064094
    Natural varianti201 – 2011I → K in CLCD. 1 Publication
    VAR_064095
    Natural varianti205 – 2051T → R in CLCD. 1 Publication
    VAR_012146
    Natural varianti209 – 2091Q → H in CLCD. 1 Publication
    VAR_064096
    Natural varianti209 – 2091Q → R in CLCD. 1 Publication
    VAR_012147
    Natural varianti211 – 2111A → P in CLCD. 1 Publication
    VAR_064097
    Natural varianti218 – 2181K → E in CLCD. 1 Publication
    VAR_064098
    Natural varianti218 – 2181K → N in CLCD; has severely impaired DNA binding and transactivation. 1 Publication
    VAR_064099
    Natural varianti218 – 2181K → Q in CLCD. 1 Publication
    VAR_064100
    Natural varianti220 – 2201T → I in CLCD; has severely impaired DNA binding and transactivation. 1 Publication
    VAR_064101
    Natural varianti225 – 2251R → L in CLCD. 1 Publication
    VAR_064102
    Natural varianti225 – 2251R → Q in CLCD; interferes with nuclear localization; abolishes DNA binding. 5 Publications
    VAR_012148
    Natural varianti225 – 2251R → W in CLCD; interferes with nuclear localization; has severely impaired DNA binding and transactivation. 4 Publications
    VAR_012149
    Natural varianti228 – 2281R → G in CLCD. 1 Publication
    VAR_064103
    Natural varianti233 – 2331K → R in CLCD. 1 Publication
    VAR_064104
    Natural varianti287 – 2871D → N in CLCD. 1 Publication
    VAR_064105
    Natural varianti362 – 3621A → V in CLCD. 1 Publication
    VAR_064106
    Natural varianti420 – 4201T → I in CLCD. 1 Publication
    VAR_064107
    Natural varianti420 – 4201T → N in CLCD. 1 Publication
    VAR_064108
    Natural varianti511 – 5111G → S in CLCD; unknown pathological significance. 1 Publication
    Corresponds to variant rs11498198 [ dbSNP | Ensembl ].
    VAR_012150
    Metaphyseal dysplasia with maxillary hypoplasia with or without brachydactyly (MDMHB) [MIM:156510]: An autosomal dominant bone dysplasia characterized by metaphyseal flaring of long bones, enlargement of the medial halves of the clavicles, maxillary hypoplasia, variable brachydactyly, and dystrophic teeth.1 Publication
    Note: The disease is caused by mutations affecting the gene represented in this entry. Analysis for copy-number variations revealed that a 105 kb duplication within RUNX2 segregated with the MDMHB phenotype in a region with maximum linkage. Real-time PCR for copy-number variation in genomic DNA in eight samples, as well as sequence analysis of fibroblast cDNA from one subject with MDMHB confirmed that affected family members were heterozygous for the presence of an intragenic duplication encompassing exons 3 to 5 of RUNX2. These three exons code for the Q/A domain and the functionally essential DNA-binding Runt domain of RUNX2. The RUNX2 duplication found in individuals with MDMHB leads to a gain of function (PubMed:23290074).1 Publication

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi451 – 4511S → A: Reduced DNA-binding and impaired phosphorylation. 1 Publication

    Keywords - Diseasei

    Disease mutation

    Organism-specific databases

    MIMi119600. phenotype.
    156510. phenotype.
    Orphaneti1452. Cleidocranial dysplasia.
    2504. Metaphyseal dysplasia - maxillary hypoplasia - brachydacty.
    PharmGKBiPA34885.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 521521Runt-related transcription factor 2PRO_0000174659Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei451 – 4511Phosphoserine; by CDK11 Publication

    Post-translational modificationi

    Phosphorylated; probably by MAP kinases (MAPK). Phosphorylation by HIPK3 is required for the SPEN/MINT and FGF2 transactivation during osteoblastic differentiation By similarity. Phosphorylation at Ser-451 by CDK1 promotes endothelial cell proliferation required for tumor angiogenesis probably by facilitating cell cycle progression. Isoform 3 is phosphorylated on Ser-340.By similarity1 Publication

    Keywords - PTMi

    Phosphoprotein

    Proteomic databases

    MaxQBiQ13950.
    PaxDbiQ13950.
    PRIDEiQ13950.

    PTM databases

    PhosphoSiteiQ13950.

    Expressioni

    Tissue specificityi

    Specifically expressed in osteoblasts.

    Gene expression databases

    ArrayExpressiQ13950.
    BgeeiQ13950.
    CleanExiHS_RUNX2.
    GenevestigatoriQ13950.

    Organism-specific databases

    HPAiCAB008374.
    CAB062561.
    HPA022040.

    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 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. This interaction is prevented on insulin or IGF1 stimulation as FOXO1 is exported from the nucleus By similarity. Interacts with CCNB1, KAT6A and KAT6B.By similarity3 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    PIN1Q135267EBI-976402,EBI-714158
    SMAD6O435413EBI-976402,EBI-976374

    Protein-protein interaction databases

    BioGridi107308. 43 interactions.
    DIPiDIP-36707N.
    IntActiQ13950. 5 interactions.
    MINTiMINT-219985.
    STRINGi9606.ENSP00000352514.

    Structurei

    3D structure databases

    ProteinModelPortaliQ13950.
    SMRiQ13950. Positions 103-252.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini101 – 229129RuntPROSITE-ProRule annotationAdd
    BLAST

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni242 – 25817Required for interaction with FOXO1By similarityAdd
    BLAST
    Regioni336 – 439104Interaction with KAT6ABy similarityAdd
    BLAST
    Regioni374 – 46895Interaction with KAT6BAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi49 – 7123Poly-GlnAdd
    BLAST
    Compositional biasi73 – 8917Poly-AlaAdd
    BLAST
    Compositional biasi237 – 521285Pro/Ser/Thr-richAdd
    BLAST

    Domaini

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

    Sequence similaritiesi

    Contains 1 Runt domain.PROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG123889.
    HOGENOMiHOG000045616.
    HOVERGENiHBG060268.
    InParanoidiQ13950.
    KOiK09278.
    PhylomeDBiQ13950.
    TreeFamiTF321496.

    Family and domain databases

    Gene3Di2.60.40.720. 1 hit.
    4.10.770.10. 1 hit.
    InterProiIPR000040. 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]
    PANTHERiPTHR11950. PTHR11950. 1 hit.
    PfamiPF00853. Runt. 1 hit.
    PF08504. RunxI. 1 hit.
    [Graphical view]
    PIRSFiPIRSF009374. TF_Runt-rel_RUNX. 1 hit.
    PRINTSiPR00967. ONCOGENEAML1.
    SUPFAMiSSF49417. SSF49417. 1 hit.
    PROSITEiPS51062. RUNT. 1 hit.
    [Graphical view]

    Sequences (3)i

    Sequence statusi: Complete.

    This entry describes 3 isoformsi produced by alternative splicing. Align

    Isoform 1 (identifier: Q13950-1) [UniParc]FASTAAdd to Basket

    Also known as: Cbfa1a

    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

    MASNSLFSTV TPCQQNFFWD PSTSRRFSPP SSSLQPGKMS DVSPVVAAQQ    50
    QQQQQQQQQQ QQQQQQQQQQ QEAAAAAAAA AAAAAAAAAV PRLRPPHDNR 100
    TMVEIIADHP AELVRTDSPN FLCSVLPSHW RCNKTLPVAF KVVALGEVPD 150
    GTVVTVMAGN DENYSAELRN ASAVMKNQVA RFNDLRFVGR SGRGKSFTLT 200
    ITVFTNPPQV ATYHRAIKVT VDGPREPRRH RQKLDDSKPS LFSDRLSDLG 250
    RIPHPSMRVG VPPQNPRPSL NSAPSPFNPQ GQSQITDPRQ AQSSPPWSYD 300
    QSYPSYLSQM TSPSIHSTTP LSSTRGTGLP AITDVPRRIS DDDTATSDFC 350
    LWPSTLSKKS QAGASELGPF SDPRQFPSIS SLTESRFSNP RMHYPATFTY 400
    TPPVTSGMSL GMSATTHYHT YLPPPYPGSS QSQSGPFQTS STPYLYYGTS 450
    SGSYQFPMVP GGDRSPSRML PPCTTTSNGS TLLNPNLPNQ NDGVDADGSH 500
    SSSPTVLNSS GRMDESVWRP Y 521
    Length:521
    Mass (Da):56,648
    Last modified:November 2, 2001 - v2
    Checksum:i44C4F3867D6F3EB1
    GO
    Isoform 2 (identifier: Q13950-2) [UniParc]FASTAAdd to Basket

    The sequence of this isoform differs from the canonical sequence as follows:
         1-19: MASNSLFSTVTPCQQNFFW → MRIPV

    Show »
    Length:507
    Mass (Da):55,054
    Checksum:i7228C267328DE1DC
    GO
    Isoform 3 (identifier: Q13950-3) [UniParc]FASTAAdd to Basket

    Also known as: Cbfa1b

    The sequence of this isoform differs from the canonical sequence as follows:
         341-362: Missing.

    Note: Contains a phosphoserine at position 340.

    Show »
    Length:499
    Mass (Da):54,249
    Checksum:i4BA956230C96EB2E
    GO

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti16 – 161N → S in AAC77441. (PubMed:9651525)Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti53 – 531Q → L in CLCD. 1 Publication
    VAR_064081
    Natural varianti78 – 836Missing.1 Publication
    VAR_012131
    Natural varianti84 – 841A → AAAAAAAAAAA in CLCD associated with brachydactyly of hands and feet. 1 Publication
    VAR_012130
    Natural varianti113 – 1131L → R in CLCD. 1 Publication
    VAR_012132
    Natural varianti118 – 1181S → N in CLCD. 1 Publication
    VAR_064082
    Natural varianti118 – 1181S → R in CLCD. 1 Publication
    VAR_012133
    Natural varianti121 – 1211F → C in CLCD. 1 Publication
    VAR_012134
    Natural varianti123 – 1231C → R in CLCD. 1 Publication
    VAR_012135
    Natural varianti131 – 1311R → C in CLCD. 1 Publication
    VAR_064083
    Natural varianti131 – 1311R → G in CLCD. 1 Publication
    VAR_064084
    Natural varianti131 – 1311R → S in CLCD. 1 Publication
    VAR_064085
    Natural varianti133 – 1331Missing in CLCD. 1 Publication
    VAR_012136
    Natural varianti136 – 1361L → P in CLCD. 1 Publication
    VAR_064086
    Natural varianti156 – 1561V → D in CLCD. 1 Publication
    VAR_064087
    Natural varianti156 – 1561V → G in CLCD. 1 Publication
    VAR_064088
    Natural varianti169 – 1691R → P in CLCD. 2 Publications
    VAR_064089
    Natural varianti169 – 1691R → Q in CLCD. 1 Publication
    VAR_012137
    Natural varianti175 – 1751M → K in CLCD. 1 Publication
    VAR_064090
    Natural varianti175 – 1751M → R in CLCD; abolishes DNA binding. 2 Publications
    VAR_012138
    Natural varianti175 – 1751M → V in CLCD. 1 Publication
    VAR_064091
    Natural varianti187 – 1871F → S in CLCD. 1 Publication
    VAR_064092
    Natural varianti190 – 1901R → Q in CLCD; abolishes DNA binding. 1 Publication
    VAR_012139
    Natural varianti190 – 1901R → W in CLCD; has severely impaired DNA binding and transactivation. 3 Publications
    VAR_012140
    Natural varianti191 – 1911S → N in CLCD; abolishes DNA binding. 2 Publications
    VAR_012141
    Natural varianti193 – 1931R → C in CLCD. 1 Publication
    VAR_012142
    Natural varianti193 – 1931R → Q in CLCD. 1 Publication
    VAR_064093
    Natural varianti197 – 1971F → S in CLCD; retains heterodimerization activity together with a trace potential for DNA binding; retains a low but still substantial transactivation activity. 2 Publications
    VAR_012143
    Natural varianti199 – 1991L → F in CLCD; abolishes DNA binding. 1 Publication
    VAR_012144
    Natural varianti200 – 2001T → A in CLCD; mild; associated also with isolated dental anomalies; normal DNA binding. 1 Publication
    VAR_012145
    Natural varianti200 – 2001T → I in CLCD. 1 Publication
    VAR_064094
    Natural varianti201 – 2011I → K in CLCD. 1 Publication
    VAR_064095
    Natural varianti205 – 2051T → R in CLCD. 1 Publication
    VAR_012146
    Natural varianti209 – 2091Q → H in CLCD. 1 Publication
    VAR_064096
    Natural varianti209 – 2091Q → R in CLCD. 1 Publication
    VAR_012147
    Natural varianti211 – 2111A → P in CLCD. 1 Publication
    VAR_064097
    Natural varianti218 – 2181K → E in CLCD. 1 Publication
    VAR_064098
    Natural varianti218 – 2181K → N in CLCD; has severely impaired DNA binding and transactivation. 1 Publication
    VAR_064099
    Natural varianti218 – 2181K → Q in CLCD. 1 Publication
    VAR_064100
    Natural varianti220 – 2201T → I in CLCD; has severely impaired DNA binding and transactivation. 1 Publication
    VAR_064101
    Natural varianti225 – 2251R → L in CLCD. 1 Publication
    VAR_064102
    Natural varianti225 – 2251R → Q in CLCD; interferes with nuclear localization; abolishes DNA binding. 5 Publications
    VAR_012148
    Natural varianti225 – 2251R → W in CLCD; interferes with nuclear localization; has severely impaired DNA binding and transactivation. 4 Publications
    VAR_012149
    Natural varianti228 – 2281R → G in CLCD. 1 Publication
    VAR_064103
    Natural varianti233 – 2331K → R in CLCD. 1 Publication
    VAR_064104
    Natural varianti287 – 2871D → N in CLCD. 1 Publication
    VAR_064105
    Natural varianti362 – 3621A → V in CLCD. 1 Publication
    VAR_064106
    Natural varianti420 – 4201T → I in CLCD. 1 Publication
    VAR_064107
    Natural varianti420 – 4201T → N in CLCD. 1 Publication
    VAR_064108
    Natural varianti511 – 5111G → S in CLCD; unknown pathological significance. 1 Publication
    Corresponds to variant rs11498198 [ dbSNP | Ensembl ].
    VAR_012150

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 1919MASNS…QNFFW → MRIPV in isoform 2. CuratedVSP_005937Add
    BLAST
    Alternative sequencei341 – 36222Missing in isoform 3. 1 PublicationVSP_005938Add
    BLAST

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF001450
    , AF001443, AF001444, AF001445, AF001446, AF001447, AF001448, AF001449 Genomic DNA. Translation: AAB65159.2.
    AF001450
    , AF001444, AF001445, AF001446, AF001447, AF001448, AF001449 Genomic DNA. Translation: AAB65158.1.
    AL161907, AL096865, AL358135 Genomic DNA. Translation: CAI19638.1.
    AL161907, AL096865, AL358135 Genomic DNA. Translation: CAI19639.1.
    AL358135, AL096865, AL161907 Genomic DNA. Translation: CAI13528.1.
    AL358135, AL096865, AL161907 Genomic DNA. Translation: CAI13531.1.
    AL096865, AL161907, AL358135 Genomic DNA. Translation: CAI19925.1.
    AL096865, AL161907, AL358135 Genomic DNA. Translation: CAI19931.1.
    AF053952 mRNA. Translation: AAC78624.1.
    AF053949 Genomic DNA. Translation: AAC77441.1.
    L40992 mRNA. Translation: AAA89072.1.
    CCDSiCCDS43467.2. [Q13950-1]
    CCDS43468.2. [Q13950-3]
    RefSeqiNP_001015051.3. NM_001015051.3. [Q13950-3]
    NP_001019801.3. NM_001024630.3. [Q13950-1]
    XP_006715294.1. XM_006715231.1. [Q13950-2]
    UniGeneiHs.535845.

    Genome annotation databases

    EnsembliENST00000359524; ENSP00000352514; ENSG00000124813. [Q13950-2]
    ENST00000371436; ENSP00000360491; ENSG00000124813. [Q13950-3]
    ENST00000371438; ENSP00000360493; ENSG00000124813. [Q13950-1]
    ENST00000465038; ENSP00000420707; ENSG00000124813. [Q13950-1]
    GeneIDi860.
    KEGGihsa:860.
    UCSCiuc003oxt.3. human. [Q13950-2]
    uc011dvx.2. human. [Q13950-1]
    uc011dvy.2. human. [Q13950-3]

    Polymorphism databases

    DMDMi17368460.

    Keywords - Coding sequence diversityi

    Alternative splicing, Polymorphism

    Cross-referencesi

    Web resourcesi

    Atlas of Genetics and Cytogenetics in Oncology and Haematology

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AF001450
    , AF001443 , AF001444 , AF001445 , AF001446 , AF001447 , AF001448 , AF001449 Genomic DNA. Translation: AAB65159.2 .
    AF001450
    , AF001444 , AF001445 , AF001446 , AF001447 , AF001448 , AF001449 Genomic DNA. Translation: AAB65158.1 .
    AL161907 , AL096865 , AL358135 Genomic DNA. Translation: CAI19638.1 .
    AL161907 , AL096865 , AL358135 Genomic DNA. Translation: CAI19639.1 .
    AL358135 , AL096865 , AL161907 Genomic DNA. Translation: CAI13528.1 .
    AL358135 , AL096865 , AL161907 Genomic DNA. Translation: CAI13531.1 .
    AL096865 , AL161907 , AL358135 Genomic DNA. Translation: CAI19925.1 .
    AL096865 , AL161907 , AL358135 Genomic DNA. Translation: CAI19931.1 .
    AF053952 mRNA. Translation: AAC78624.1 .
    AF053949 Genomic DNA. Translation: AAC77441.1 .
    L40992 mRNA. Translation: AAA89072.1 .
    CCDSi CCDS43467.2. [Q13950-1 ]
    CCDS43468.2. [Q13950-3 ]
    RefSeqi NP_001015051.3. NM_001015051.3. [Q13950-3 ]
    NP_001019801.3. NM_001024630.3. [Q13950-1 ]
    XP_006715294.1. XM_006715231.1. [Q13950-2 ]
    UniGenei Hs.535845.

    3D structure databases

    ProteinModelPortali Q13950.
    SMRi Q13950. Positions 103-252.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 107308. 43 interactions.
    DIPi DIP-36707N.
    IntActi Q13950. 5 interactions.
    MINTi MINT-219985.
    STRINGi 9606.ENSP00000352514.

    PTM databases

    PhosphoSitei Q13950.

    Polymorphism databases

    DMDMi 17368460.

    Proteomic databases

    MaxQBi Q13950.
    PaxDbi Q13950.
    PRIDEi Q13950.

    Protocols and materials databases

    DNASUi 860.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000359524 ; ENSP00000352514 ; ENSG00000124813 . [Q13950-2 ]
    ENST00000371436 ; ENSP00000360491 ; ENSG00000124813 . [Q13950-3 ]
    ENST00000371438 ; ENSP00000360493 ; ENSG00000124813 . [Q13950-1 ]
    ENST00000465038 ; ENSP00000420707 ; ENSG00000124813 . [Q13950-1 ]
    GeneIDi 860.
    KEGGi hsa:860.
    UCSCi uc003oxt.3. human. [Q13950-2 ]
    uc011dvx.2. human. [Q13950-1 ]
    uc011dvy.2. human. [Q13950-3 ]

    Organism-specific databases

    CTDi 860.
    GeneCardsi GC06P045295.
    GeneReviewsi RUNX2.
    HGNCi HGNC:10472. RUNX2.
    HPAi CAB008374.
    CAB062561.
    HPA022040.
    MIMi 119600. phenotype.
    156510. phenotype.
    600211. gene.
    neXtProti NX_Q13950.
    Orphaneti 1452. Cleidocranial dysplasia.
    2504. Metaphyseal dysplasia - maxillary hypoplasia - brachydacty.
    PharmGKBi PA34885.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG123889.
    HOGENOMi HOG000045616.
    HOVERGENi HBG060268.
    InParanoidi Q13950.
    KOi K09278.
    PhylomeDBi Q13950.
    TreeFami TF321496.

    Enzyme and pathway databases

    Reactomei REACT_118713. YAP1- and WWTR1 (TAZ)-stimulated gene expression.
    SignaLinki Q13950.

    Miscellaneous databases

    GeneWikii RUNX2.
    GenomeRNAii 860.
    NextBioi 3572.
    PROi Q13950.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q13950.
    Bgeei Q13950.
    CleanExi HS_RUNX2.
    Genevestigatori Q13950.

    Family and domain databases

    Gene3Di 2.60.40.720. 1 hit.
    4.10.770.10. 1 hit.
    InterProi 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.
    [Graphical view ]
    PANTHERi PTHR11950. PTHR11950. 1 hit.
    Pfami PF00853. Runt. 1 hit.
    PF08504. RunxI. 1 hit.
    [Graphical view ]
    PIRSFi PIRSF009374. TF_Runt-rel_RUNX. 1 hit.
    PRINTSi PR00967. ONCOGENEAML1.
    SUPFAMi SSF49417. SSF49417. 1 hit.
    PROSITEi PS51062. RUNT. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2), VARIANT CLCD ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-84 INS, VARIANT 78-ALA--ALA-83 DEL.
    2. "Genomic organization, expression of the human CBFA1 gene, and evidence for an alternative splicing event affecting protein function."
      Geoffroy V., Corral D.A., Zhou L., Lee B., Karsenty G.
      Mamm. Genome 9:54-57(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING (ISOFORMS 1 AND 3).
    3. "The DNA sequence and analysis of human chromosome 6."
      Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., Andrews T.D.
      , Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.
      Nature 425:805-811(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    4. "Genomic structure and isoform expression of the mouse, rat and human Cbfa1/Osf2 transcription factor."
      Xiao Z.S., Thomas R., Hinson T.K., Quarles L.D.
      Gene 214:187-197(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-19 (ISOFORM 1).
    5. "The cDNA cloning of the transcripts of human PEBP2alphaA/CBFA1 mapped to 6p12.3-p21.1, the locus for cleidocranial dysplasia."
      Zhang Y.-W., Bae S.-C., Takahashi E., Ito Y.
      Oncogene 15:367-371(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 60-521 (ISOFORM 3).
    6. "Regulation of osteocalcin gene expression by a novel Ku antigen transcription factor complex."
      Willis D.M., Loewy A.P., Charlton-Kachigian N., Shao J.-S., Ornitz D.M., Towler D.A.
      J. Biol. Chem. 277:37280-37291(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH XRCC5 AND XRCC6.
      Tissue: Osteoblast.
    7. "MOZ and MORF histone acetyltransferases interact with the Runt-domain transcription factor Runx2."
      Pelletier N., Champagne N., Stifani S., Yang X.-J.
      Oncogene 21:2729-2740(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH KAT6A AND KAT6B, FUNCTION.
    8. "Cell cycle-dependent phosphorylation of the RUNX2 transcription factor by cdc2 regulates endothelial cell proliferation."
      Qiao M., Shapiro P., Fosbrink M., Rus H., Kumar R., Passaniti A.
      J. Biol. Chem. 281:7118-7128(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CCNB1, PHOSPHORYLATION AT SER-451 BY CDK1, MUTAGENESIS OF SER-451.
    9. "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-340 (ISOFORM 3), IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    10. Cited for: INVOLVEMENT IN MDMHB.
    11. "Missense mutations abolishing DNA binding of the osteoblast-specific transcription factor OSF2/CBFA1 in cleidocranial dysplasia."
      Lee B., Thirunavukkarasu K., Zhou L., Pastore L., Baldini A., Hecht J., Geoffroy V., Ducy P., Karsenty G.
      Nat. Genet. 16:307-310(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS CLCD ARG-175 AND ASN-191.
    12. Cited for: VARIANTS CLCD ARG-113; ARG-118; CYS-121; ARG-123; ARG-205; GLN-225; TRP-225 AND SER-511.
    13. "CBFA1 mutation analysis and functional correlation with phenotypic variability in cleidocranial dysplasia."
      Zhou G., Chen Y., Zhou L., Thirunavukkarasu K., Hecht J., Chitayat D., Gelb B.D., Pirinen S., Berry S.A., Greenberg C.R., Karsenty G., Lee B.
      Hum. Mol. Genet. 8:2311-2316(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS CLCD ASN-133 DEL; GLN-169; ARG-175; GLN-190; ASN-191; CYS-193; PHE-199; ALA-200; ARG-209 AND GLN-225.
    14. "PEBP2alphaA/CBFA1 mutations in Japanese cleidocranial dysplasia patients."
      Zhang Y.-W., Yasui N., Kakazu N., Abe T., Takada K., Imai S., Sato M., Nomura S., Ochi T., Okuzumi S., Nogami H., Nagai T., Ohashi H., Ito Y.
      Gene 244:21-28(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CLCD SER-197.
    15. "A novel CBFA1 mutation (R190W) in an Italian family with cleidocranial dysplasia."
      Giannotti A., Tessa A., Patrono C., De Florio L., Velardo M., Dionisi-Vici C., Bertini E., Santorelli F.M.
      Hum. Mutat. 16:277-277(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CLCD TRP-190.
    16. "Functional analysis of RUNX2 mutations in Japanese patients with cleidocranial dysplasia demonstrates novel genotype-phenotype correlations."
      Yoshida T., Kanegane H., Osato M., Yanagida M., Miyawaki T., Ito Y., Shigesada K.
      Am. J. Hum. Genet. 71:724-738(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS CLCD TRP-190; SER-197; ASN-218; ILE-220; TRP-225 AND GLN-225, CHARACTERIZATION OF VARIANTS CLCD TRP-190; SER-197; ASN-218; ILE-220; TRP-225 AND GLN-225.
    17. "New mutations in the CBFA1 gene in two Mexican patients with cleidocranial dysplasia."
      Machuca-Tzili L., Monroy-Jaramillo N., Gonzalez-del Angel A., Kofman-Alfaro S.
      Clin. Genet. 61:349-353(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CLCD LEU-53.
    18. "Cleidocranial dysplasia with decreased bone density and biochemical findings of hypophosphatasia."
      Morava E., Karteszi J., Weisenbach J., Caliebe A., Mundlos S., Mehes K.
      Eur. J. Pediatr. 161:619-622(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CLCD PRO-169.
    19. "Mutations in the RUNX2 gene in patients with cleidocranial dysplasia."
      Otto F., Kanegane H., Mundlos S.
      Hum. Mutat. 19:209-216(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS CLCD GLY-156; PRO-169; TRP-190; LYS-201; TRP-225; GLN-225 AND VAL-362.
    20. "Four novel RUNX2 mutations including a splice donor site result in the cleidocranial dysplasia phenotype."
      Kim H.-J., Nam S.-H., Kim H.-J., Park H.-S., Ryoo H.-M., Kim S.-Y., Cho T.-J., Kim S.-G., Bae S.-C., Kim I.-S., Stein J.L., van Wijnen A.J., Stein G.S., Lian J.B., Choi J.-Y.
      J. Cell. Physiol. 207:114-122(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANTS CLCD GLY-131 AND GLN-225.
    21. "A novel RUNX2 mutation (T420I) in Chinese patients with cleidocranial dysplasia."
      Wang G.X., Sun R.P., Song F.L.
      Genet. Mol. Res. 9:41-47(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CLCD ILE-420.
    22. Cited for: VARIANTS CLCD ASN-118; SER-131; CYS-131; PRO-136; ASP-156; VAL-175; LYS-175; SER-187; GLN-193; ILE-200; HIS-209; PRO-211; GLN-218; GLU-218; LEU-225; GLY-228; ARG-233; ASN-287 AND ASN-420.
    23. "RUNX2 mutations in cleidocranial dysplasia patients."
      Ryoo H.M., Kang H.Y., Lee S.K., Lee K.E., Kim J.W.
      Oral Dis. 16:55-60(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: VARIANT CLCD TRP-225.

    Entry informationi

    Entry nameiRUNX2_HUMAN
    AccessioniPrimary (citable) accession number: Q13950
    Secondary accession number(s): O14614, O14615, O95181
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 2, 2001
    Last sequence update: November 2, 2001
    Last modified: October 1, 2014
    This is version 151 of the entry and version 2 of the sequence. [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 6
      Human chromosome 6: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3