ID RUNX2_HUMAN Reviewed; 521 AA. AC Q13950; O14614; O14615; O95181; DT 02-NOV-2001, integrated into UniProtKB/Swiss-Prot. DT 02-NOV-2001, sequence version 2. DT 11-NOV-2015, entry version 163. DE RecName: Full=Runt-related transcription factor 2; DE AltName: Full=Acute myeloid leukemia 3 protein; DE AltName: Full=Core-binding factor subunit alpha-1; DE Short=CBF-alpha-1; DE AltName: Full=Oncogene AML-3; DE AltName: Full=Osteoblast-specific transcription factor 2; DE Short=OSF-2; DE AltName: Full=Polyomavirus enhancer-binding protein 2 alpha A subunit; DE Short=PEA2-alpha A; DE Short=PEBP2-alpha A; DE AltName: Full=SL3-3 enhancer factor 1 alpha A subunit; DE AltName: Full=SL3/AKV core-binding factor alpha A subunit; GN Name=RUNX2; Synonyms=AML3, CBFA1, OSF2, PEBP2A; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORMS 1 AND 2), VARIANT CLCD RP ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-ALA-84 INS, AND VARIANT RP 78-ALA--ALA-83 DEL. RX PubMed=9182765; DOI=10.1016/S0092-8674(00)80260-3; RA Mundlos S., Otto F., Mundlos C., Mulliken J.B., Aylsworth A.S., RA Albright S., Lindhout D., Cole W.G., Henn W., Knoll J.H.M., Owen M.J., RA Mertelsmann R., Zabel B.U., Olsen B.R.; RT "Mutations involving the transcription factor CBFA1 cause RT cleidocranial dysplasia."; RL Cell 89:773-779(1997). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORMS RP 1 AND 3). RX PubMed=9434946; DOI=10.1007/s003359900679; RA Geoffroy V., Corral D.A., Zhou L., Lee B., Karsenty G.; RT "Genomic organization, expression of the human CBFA1 gene, and RT evidence for an alternative splicing event affecting protein RT function."; RL Mamm. Genome 9:54-57(1998). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., RA Gilbert J.G.R., Clamp M.E., Bethel G., Milne S., Ainscough R., RA Almeida J.P., Ambrose K.D., Andrews T.D., Ashwell R.I.S., RA Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Barker D.J., RA Barlow K.F., Bates K., Beare D.M., Beasley H., Beasley O., Bird C.P., RA Blakey S.E., Bray-Allen S., Brook J., Brown A.J., Brown J.Y., RA Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., RA Ellington A.E., Evans K.A., Faulkner L., Francis M.D., Frankish A., RA Frankland J., French L., Garner P., Garnett J., Ghori M.J., RA Gilby L.M., Gillson C.J., Glithero R.J., Grafham D.V., Grant M., RA Gribble S., Griffiths C., Griffiths M.N.D., Hall R., Halls K.S., RA Hammond S., Harley J.L., Hart E.A., Heath P.D., Heathcott R., RA Holmes S.J., Howden P.J., Howe K.L., Howell G.R., Huckle E., RA Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., Joy A.A., RA Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., Langford C., RA Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., Lloyd D.M., RA Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., RA McMurray A., Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., RA Novik K.L., Oliver K., Overton-Larty E.K., Parker A., Patel R., RA Pearce A.V., Peck A.I., Phillimore B.J.C.T., Phillips S., Plumb R.W., RA Porter K.M., Ramsey Y., Ranby S.A., Rice C.M., Ross M.T., Searle S.M., RA Sehra H.K., Sheridan E., Skuce C.D., Smith S., Smith M., Spraggon L., RA Squares S.L., Steward C.A., Sycamore N., Tamlyn-Hall G., Tester J., RA Theaker A.J., Thomas D.W., Thorpe A., Tracey A., Tromans A., Tubby B., RA Wall M., Wallis J.M., West A.P., White S.S., Whitehead S.L., RA Whittaker H., Wild A., Willey D.J., Wilmer T.E., Wood J.M., Wray P.W., RA Wyatt J.C., Young L., Younger R.M., Bentley D.R., Coulson A., RA Durbin R.M., Hubbard T., Sulston J.E., Dunham I., Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] OF 1-19 (ISOFORM 1). RX PubMed=9651525; DOI=10.1016/S0378-1119(98)00227-3; RA Xiao Z.S., Thomas R., Hinson T.K., Quarles L.D.; RT "Genomic structure and isoform expression of the mouse, rat and human RT Cbfa1/Osf2 transcription factor."; RL Gene 214:187-197(1998). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] OF 60-521 (ISOFORM 3). RX PubMed=9233771; DOI=10.1038/sj.onc.1201352; RA Zhang Y.-W., Bae S.-C., Takahashi E., Ito Y.; RT "The cDNA cloning of the transcripts of human PEBP2alphaA/CBFA1 mapped RT to 6p12.3-p21.1, the locus for cleidocranial dysplasia."; RL Oncogene 15:367-371(1997). RN [6] RP INTERACTION WITH XRCC5 AND XRCC6. RC TISSUE=Osteoblast; RX PubMed=12145306; DOI=10.1074/jbc.M206482200; RA Willis D.M., Loewy A.P., Charlton-Kachigian N., Shao J.-S., RA Ornitz D.M., Towler D.A.; RT "Regulation of osteocalcin gene expression by a novel Ku antigen RT transcription factor complex."; RL J. Biol. Chem. 277:37280-37291(2002). RN [7] RP INTERACTION WITH KAT6A AND KAT6B, AND FUNCTION. RX PubMed=11965546; DOI=10.1038/sj.onc.1205367; RA Pelletier N., Champagne N., Stifani S., Yang X.-J.; RT "MOZ and MORF histone acetyltransferases interact with the Runt-domain RT transcription factor Runx2."; RL Oncogene 21:2729-2740(2002). RN [8] RP INTERACTION WITH CCNB1, PHOSPHORYLATION AT SER-451 BY CDK1, AND RP MUTAGENESIS OF SER-451. RX PubMed=16407259; DOI=10.1074/jbc.M508162200; RA Qiao M., Shapiro P., Fosbrink M., Rus H., Kumar R., Passaniti A.; RT "Cell cycle-dependent phosphorylation of the RUNX2 transcription RT factor by cdc2 regulates endothelial cell proliferation."; RL J. Biol. Chem. 281:7118-7128(2006). RN [9] RP INTERACTION WITH FOXP3. RX PubMed=17377532; DOI=10.1038/nature05673; RA Ono M., Yaguchi H., Ohkura N., Kitabayashi I., Nagamura Y., Nomura T., RA Miyachi Y., Tsukada T., Sakaguchi S.; RT "Foxp3 controls regulatory T-cell function by interacting with RT AML1/Runx1."; RL Nature 446:685-689(2007). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-340 (ISOFORM 3), AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18220336; DOI=10.1021/pr0705441; RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., RA Yates J.R. III; RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for RT efficient phosphoproteomic analysis."; RL J. Proteome Res. 7:1346-1351(2008). RN [11] RP INVOLVEMENT IN MDMHB. RX PubMed=23290074; DOI=10.1016/j.ajhg.2012.12.001; RG FORGE Canada Consortium; RA Moffatt P., Ben Amor M., Glorieux F.H., Roschger P., Klaushofer K., RA Schwartzentruber J.A., Paterson A.D., Hu P., Marshall C., RA Fahiminiya S., Majewski J., Beaulieu C.L., Boycott K.M., Rauch F.; RT "Metaphyseal dysplasia with maxillary hypoplasia and brachydactyly is RT caused by a duplication in RUNX2."; RL Am. J. Hum. Genet. 92:252-258(2013). RN [12] RP VARIANTS CLCD ARG-175 AND ASN-191. RX PubMed=9207800; DOI=10.1038/ng0797-307; RA Lee B., Thirunavukkarasu K., Zhou L., Pastore L., Baldini A., RA Hecht J., Geoffroy V., Ducy P., Karsenty G.; RT "Missense mutations abolishing DNA binding of the osteoblast-specific RT transcription factor OSF2/CBFA1 in cleidocranial dysplasia."; RL Nat. Genet. 16:307-310(1997). RN [13] RP VARIANTS CLCD ARG-113; ARG-118; CYS-121; ARG-123; ARG-205; GLN-225; RP TRP-225 AND SER-511. RX PubMed=10521292; DOI=10.1086/302622; RA Quack I., Vonderstrass B., Stock M., Aylsworth A.S., Becker A., RA Brueton L., Lee P.J., Majewski F., Mulliken J.B., Suri M., Zenker M., RA Mundlos S., Otto F.; RT "Mutation analysis of core binding factor A1 in patients with RT cleidocranial dysplasia."; RL Am. J. Hum. Genet. 65:1268-1278(1999). RN [14] RP VARIANTS CLCD ASN-133 DEL; GLN-169; ARG-175; GLN-190; ASN-191; RP CYS-193; PHE-199; ALA-200; ARG-209 AND GLN-225. RX PubMed=10545612; DOI=10.1093/hmg/8.12.2311; RA Zhou G., Chen Y., Zhou L., Thirunavukkarasu K., Hecht J., Chitayat D., RA Gelb B.D., Pirinen S., Berry S.A., Greenberg C.R., Karsenty G., RA Lee B.; RT "CBFA1 mutation analysis and functional correlation with phenotypic RT variability in cleidocranial dysplasia."; RL Hum. Mol. Genet. 8:2311-2316(1999). RN [15] RP VARIANT CLCD SER-197. RX PubMed=10689183; DOI=10.1016/S0378-1119(99)00558-2; RA Zhang Y.-W., Yasui N., Kakazu N., Abe T., Takada K., Imai S., Sato M., RA Nomura S., Ochi T., Okuzumi S., Nogami H., Nagai T., Ohashi H., RA Ito Y.; RT "PEBP2alphaA/CBFA1 mutations in Japanese cleidocranial dysplasia RT patients."; RL Gene 244:21-28(2000). RN [16] RP VARIANT CLCD TRP-190. RX PubMed=10980549; RX DOI=10.1002/1098-1004(200009)16:3<277::AID-HUMU25>3.0.CO;2-V; RA Giannotti A., Tessa A., Patrono C., De Florio L., Velardo M., RA Dionisi-Vici C., Bertini E., Santorelli F.M.; RT "A novel CBFA1 mutation (R190W) in an Italian family with RT cleidocranial dysplasia."; RL Hum. Mutat. 16:277-277(2000). RN [17] RP VARIANTS CLCD TRP-190; SER-197; ASN-218; ILE-220; TRP-225 AND GLN-225, RP AND CHARACTERIZATION OF VARIANTS CLCD TRP-190; SER-197; ASN-218; RP ILE-220; TRP-225 AND GLN-225. RX PubMed=12196916; DOI=10.1086/342717; RA Yoshida T., Kanegane H., Osato M., Yanagida M., Miyawaki T., Ito Y., RA Shigesada K.; RT "Functional analysis of RUNX2 mutations in Japanese patients with RT cleidocranial dysplasia demonstrates novel genotype-phenotype RT correlations."; RL Am. J. Hum. Genet. 71:724-738(2002). RN [18] RP VARIANT CLCD LEU-53. RX PubMed=12081718; DOI=10.1034/j.1399-0004.2002.610505.x; RA Machuca-Tzili L., Monroy-Jaramillo N., Gonzalez-del Angel A., RA Kofman-Alfaro S.; RT "New mutations in the CBFA1 gene in two Mexican patients with RT cleidocranial dysplasia."; RL Clin. Genet. 61:349-353(2002). RN [19] RP VARIANT CLCD PRO-169. RX PubMed=12424590; DOI=10.1007/s00431-002-0977-x; RA Morava E., Karteszi J., Weisenbach J., Caliebe A., Mundlos S., RA Mehes K.; RT "Cleidocranial dysplasia with decreased bone density and biochemical RT findings of hypophosphatasia."; RL Eur. J. Pediatr. 161:619-622(2002). RN [20] RP VARIANTS CLCD GLY-156; PRO-169; TRP-190; LYS-201; TRP-225; GLN-225 AND RP VAL-362. RX PubMed=11857736; DOI=10.1002/humu.10043; RA Otto F., Kanegane H., Mundlos S.; RT "Mutations in the RUNX2 gene in patients with cleidocranial RT dysplasia."; RL Hum. Mutat. 19:209-216(2002). RN [21] RP VARIANTS CLCD GLY-131 AND GLN-225. RX PubMed=16270353; DOI=10.1002/jcp.20552; RA Kim H.-J., Nam S.-H., Kim H.-J., Park H.-S., Ryoo H.-M., Kim S.-Y., RA Cho T.-J., Kim S.-G., Bae S.-C., Kim I.-S., Stein J.L., RA van Wijnen A.J., Stein G.S., Lian J.B., Choi J.-Y.; RT "Four novel RUNX2 mutations including a splice donor site result in RT the cleidocranial dysplasia phenotype."; RL J. Cell. Physiol. 207:114-122(2006). RN [22] RP VARIANT CLCD ILE-420. RX PubMed=20082269; DOI=10.4238/vol9-1gmr685; RA Wang G.X., Sun R.P., Song F.L.; RT "A novel RUNX2 mutation (T420I) in Chinese patients with cleidocranial RT dysplasia."; RL Genet. Mol. Res. 9:41-47(2010). RN [23] RP VARIANTS CLCD ASN-118; SER-131; CYS-131; PRO-136; ASP-156; VAL-175; RP LYS-175; SER-187; GLN-193; ILE-200; HIS-209; PRO-211; GLN-218; RP GLU-218; LEU-225; GLY-228; ARG-233; ASN-287 AND ASN-420. RX PubMed=20648631; DOI=10.1002/humu.21298; RA Ott C.E., Leschik G., Trotier F., Brueton L., Brunner H.G., RA Brussel W., Guillen-Navarro E., Haase C., Kohlhase J., Kotzot D., RA Lane A., Lee-Kirsch M.A., Morlot S., Simon M.E.H., RA Steichen-Gersdorf E., Tegay D.H., Peters H., Mundlos S., Klopocki E.; RT "Deletions of the RUNX2 gene are present in about 10% of individuals RT with cleidocranial dysplasia."; RL Hum. Mutat. 31:E1587-E1593(2010). RN [24] RP VARIANT CLCD TRP-225. RX PubMed=19744171; DOI=10.1111/j.1601-0825.2009.01623.x; RA Ryoo H.M., Kang H.Y., Lee S.K., Lee K.E., Kim J.W.; RT "RUNX2 mutations in cleidocranial dysplasia patients."; RL Oral Dis. 16:55-60(2010). CC -!- FUNCTION: Transcription factor involved in osteoblastic CC differentiation and skeletal morphogenesis. Essential for the CC maturation of osteoblasts and both intramembranous and CC endochondral ossification. CBF binds to the core site, 5'- CC PYGPYGGT-3', of a number of enhancers and promoters, including CC murine leukemia virus, polyomavirus enhancer, T-cell receptor CC enhancers, osteocalcin, osteopontin, bone sialoprotein, alpha 1(I) CC collagen, LCK, IL-3 and GM-CSF promoters. In osteoblasts, supports CC transcription activation: synergizes with SPEN/MINT to enhance CC FGFR2-mediated activation of the osteocalcin FGF-responsive CC element (OCFRE) (By similarity). Inhibits KAT6B-dependent CC transcriptional activation. {ECO:0000250, CC ECO:0000269|PubMed:11965546}. CC -!- SUBUNIT: Heterodimer of an alpha and a beta subunit. The alpha CC subunit binds DNA as a monomer and through the Runt domain. DNA- CC binding is increased by heterodimerization. Interacts with XRCC6 CC (Ku70) and XRCC5 (Ku80). Interacts with HIVEP3. Interacts with CC IFI204. Interaction with SATB2; the interaction results in CC enhanced DNA binding and transactivation by these transcription CC factors. Binds to HIPK3. Interacts (isoform 3) with DDX5. CC Interacts with FOXO1 (via a C-terminal region); the interaction CC inhibits RUNX2 transcriptional activity towards BGLAP. This CC interaction is prevented on insulin or IGF1 stimulation as FOXO1 CC is exported from the nucleus (By similarity). Interacts with CC CCNB1, KAT6A and KAT6B. Interacts with FOXP3. CC {ECO:0000250|UniProtKB:Q08775, ECO:0000269|PubMed:11965546, CC ECO:0000269|PubMed:12145306, ECO:0000269|PubMed:16407259, CC ECO:0000269|PubMed:17377532}. CC -!- INTERACTION: CC Q13526:PIN1; NbExp=7; IntAct=EBI-976402, EBI-714158; CC O43541:SMAD6; NbExp=3; IntAct=EBI-976402, EBI-976374; CC O15350:TP73; NbExp=3; IntAct=EBI-976402, EBI-389606; CC -!- SUBCELLULAR LOCATION: Nucleus. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=Cbfa1a; CC IsoId=Q13950-1; Sequence=Displayed; CC Name=2; CC IsoId=Q13950-2; Sequence=VSP_005937; CC Name=3; Synonyms=Cbfa1b; CC IsoId=Q13950-3; Sequence=VSP_005938; CC Note=Contains a phosphoserine at position 340. CC {ECO:0000244|PubMed:18220336}; CC -!- TISSUE SPECIFICITY: Specifically expressed in osteoblasts. CC -!- DOMAIN: A proline/serine/threonine rich region at the C-terminus CC is necessary for transcriptional activation of target genes and CC contains the phosphorylation sites. CC -!- PTM: Phosphorylated; probably by MAP kinases (MAPK). CC Phosphorylation by HIPK3 is required for the SPEN/MINT and FGF2 CC transactivation during osteoblastic differentiation (By CC similarity). Phosphorylation at Ser-451 by CDK1 promotes CC endothelial cell proliferation required for tumor angiogenesis CC probably by facilitating cell cycle progression. Isoform 3 is CC phosphorylated on Ser-340. {ECO:0000250, CC ECO:0000269|PubMed:16407259}. CC -!- DISEASE: Cleidocranial dysplasia (CLCD) [MIM:119600]: Autosomal CC dominant skeletal disorder with high penetrance and variable CC expressivity. It is due to defective endochondral and CC intramembranous bone formation. Typical features include CC hypoplasia/aplasia of clavicles, patent fontanelles, wormian bones CC (additional cranial plates caused by abnormal ossification of the CC calvaria), supernumerary teeth, short stature, and other skeletal CC changes. In some cases defects in RUNX2 are exclusively associated CC with dental anomalies. {ECO:0000269|PubMed:10521292, CC ECO:0000269|PubMed:10545612, ECO:0000269|PubMed:10689183, CC ECO:0000269|PubMed:10980549, ECO:0000269|PubMed:11857736, CC ECO:0000269|PubMed:12081718, ECO:0000269|PubMed:12196916, CC ECO:0000269|PubMed:12424590, ECO:0000269|PubMed:16270353, CC ECO:0000269|PubMed:19744171, ECO:0000269|PubMed:20082269, CC ECO:0000269|PubMed:20648631, ECO:0000269|PubMed:9182765, CC ECO:0000269|PubMed:9207800}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. CC -!- DISEASE: Metaphyseal dysplasia with maxillary hypoplasia with or CC without brachydactyly (MDMHB) [MIM:156510]: An autosomal dominant CC bone dysplasia characterized by metaphyseal flaring of long bones, CC enlargement of the medial halves of the clavicles, maxillary CC hypoplasia, variable brachydactyly, and dystrophic teeth. CC {ECO:0000269|PubMed:23290074}. Note=The disease is caused by CC mutations affecting the gene represented in this entry. Analysis CC for copy-number variations revealed that a 105 kb duplication CC within RUNX2 segregated with the MDMHB phenotype in a region with CC maximum linkage. Real-time PCR for copy-number variation in CC genomic DNA in eight samples, as well as sequence analysis of CC fibroblast cDNA from one subject with MDMHB confirmed that CC affected family members were heterozygous for the presence of an CC intragenic duplication encompassing exons 3 to 5 of RUNX2. These CC three exons code for the Q/A domain and the functionally essential CC DNA-binding Runt domain of RUNX2. The RUNX2 duplication found in CC individuals with MDMHB leads to a gain of function CC (PubMed:23290074). {ECO:0000269|PubMed:23290074}. CC -!- SIMILARITY: Contains 1 Runt domain. {ECO:0000255|PROSITE- CC ProRule:PRU00399}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology CC and Haematology; CC URL="http://atlasgeneticsoncology.org/Genes/RUNX2ID42183ch6p21.html"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AF001450; AAB65159.2; -; Genomic_DNA. DR EMBL; AF001443; AAB65159.2; JOINED; Genomic_DNA. DR EMBL; AF001444; AAB65159.2; JOINED; Genomic_DNA. DR EMBL; AF001445; AAB65159.2; JOINED; Genomic_DNA. DR EMBL; AF001446; AAB65159.2; JOINED; Genomic_DNA. DR EMBL; AF001447; AAB65159.2; JOINED; Genomic_DNA. DR EMBL; AF001448; AAB65159.2; JOINED; Genomic_DNA. DR EMBL; AF001449; AAB65159.2; JOINED; Genomic_DNA. DR EMBL; AF001450; AAB65158.1; -; Genomic_DNA. DR EMBL; AF001444; AAB65158.1; JOINED; Genomic_DNA. DR EMBL; AF001445; AAB65158.1; JOINED; Genomic_DNA. DR EMBL; AF001446; AAB65158.1; JOINED; Genomic_DNA. DR EMBL; AF001447; AAB65158.1; JOINED; Genomic_DNA. DR EMBL; AF001448; AAB65158.1; JOINED; Genomic_DNA. DR EMBL; AF001449; AAB65158.1; JOINED; Genomic_DNA. DR EMBL; AL161907; CAI19638.1; -; Genomic_DNA. DR EMBL; AL096865; CAI19638.1; JOINED; Genomic_DNA. DR EMBL; AL358135; CAI19638.1; JOINED; Genomic_DNA. DR EMBL; AL161907; CAI19639.1; -; Genomic_DNA. DR EMBL; AL096865; CAI19639.1; JOINED; Genomic_DNA. DR EMBL; AL358135; CAI19639.1; JOINED; Genomic_DNA. DR EMBL; AL358135; CAI13528.1; -; Genomic_DNA. DR EMBL; AL096865; CAI13528.1; JOINED; Genomic_DNA. DR EMBL; AL161907; CAI13528.1; JOINED; Genomic_DNA. DR EMBL; AL358135; CAI13531.1; -; Genomic_DNA. DR EMBL; AL096865; CAI13531.1; JOINED; Genomic_DNA. DR EMBL; AL161907; CAI13531.1; JOINED; Genomic_DNA. DR EMBL; AL096865; CAI19925.1; -; Genomic_DNA. DR EMBL; AL161907; CAI19925.1; JOINED; Genomic_DNA. DR EMBL; AL358135; CAI19925.1; JOINED; Genomic_DNA. DR EMBL; AL096865; CAI19931.1; -; Genomic_DNA. DR EMBL; AL161907; CAI19931.1; JOINED; Genomic_DNA. DR EMBL; AL358135; CAI19931.1; JOINED; Genomic_DNA. DR EMBL; AF053952; AAC78624.1; -; mRNA. DR EMBL; AF053949; AAC77441.1; -; Genomic_DNA. DR EMBL; L40992; AAA89072.1; -; mRNA. DR CCDS; CCDS43467.2; -. [Q13950-1] DR CCDS; CCDS43468.2; -. [Q13950-3] DR RefSeq; NP_001015051.3; NM_001015051.3. [Q13950-3] DR RefSeq; NP_001019801.3; NM_001024630.3. [Q13950-1] DR UniGene; Hs.535845; -. DR ProteinModelPortal; Q13950; -. DR SMR; Q13950; 103-252. DR BioGrid; 107308; 43. DR DIP; DIP-36707N; -. DR IntAct; Q13950; 6. DR MINT; MINT-219985; -. DR STRING; 9606.ENSP00000360493; -. DR PhosphoSite; Q13950; -. DR BioMuta; RUNX2; -. DR DMDM; 17368460; -. DR MaxQB; Q13950; -. DR PaxDb; Q13950; -. DR PRIDE; Q13950; -. DR DNASU; 860; -. DR Ensembl; ENST00000359524; ENSP00000352514; ENSG00000124813. [Q13950-2] DR Ensembl; ENST00000371432; ENSP00000360486; ENSG00000124813. [Q13950-3] DR Ensembl; ENST00000371436; ENSP00000360491; ENSG00000124813. [Q13950-3] DR Ensembl; ENST00000371438; ENSP00000360493; ENSG00000124813. [Q13950-1] DR Ensembl; ENST00000465038; ENSP00000420707; ENSG00000124813. [Q13950-1] DR GeneID; 860; -. DR KEGG; hsa:860; -. DR UCSC; uc003oxt.3; human. [Q13950-2] DR UCSC; uc011dvx.2; human. [Q13950-1] DR UCSC; uc011dvy.2; human. [Q13950-3] DR CTD; 860; -. DR GeneCards; RUNX2; -. DR GeneReviews; RUNX2; -. DR HGNC; HGNC:10472; RUNX2. DR HPA; CAB008374; -. DR HPA; CAB062561; -. DR HPA; CAB068226; -. DR HPA; HPA022040; -. DR MIM; 119600; phenotype. DR MIM; 156510; phenotype. DR MIM; 600211; gene. DR neXtProt; NX_Q13950; -. DR Orphanet; 1452; Cleidocranial dysplasia. DR Orphanet; 2504; Metaphyseal dysplasia - maxillary hypoplasia - brachydacty. DR PharmGKB; PA34885; -. DR eggNOG; KOG3982; Eukaryota. DR eggNOG; ENOG4111J4Y; LUCA. DR GeneTree; ENSGT00390000016964; -. DR HOGENOM; HOG000045616; -. DR HOVERGEN; HBG060268; -. DR InParanoid; Q13950; -. DR KO; K09278; -. DR OMA; XVVALGE; -. DR PhylomeDB; Q13950; -. DR TreeFam; TF321496; -. DR Reactome; R-HSA-2032785; YAP1- and WWTR1 (TAZ)-stimulated gene expression. DR SignaLink; Q13950; -. DR ChiTaRS; RUNX2; human. DR GeneWiki; RUNX2; -. DR GenomeRNAi; 860; -. DR NextBio; 3572; -. DR PRO; PR:Q13950; -. DR Proteomes; UP000005640; Chromosome 6. DR Bgee; Q13950; -. DR CleanEx; HS_RUNX2; -. DR ExpressionAtlas; Q13950; baseline and differential. DR Genevisible; Q13950; HS. DR GO; GO:0005737; C:cytoplasm; IEA:Ensembl. DR GO; GO:0000790; C:nuclear chromatin; ISS:BHF-UCL. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0005667; C:transcription factor complex; IEA:Ensembl. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. DR GO; GO:0003682; F:chromatin binding; IEA:Ensembl. DR GO; GO:0000978; F:RNA polymerase II core promoter proximal region sequence-specific DNA binding; IEA:Ensembl. DR GO; GO:0000979; F:RNA polymerase II core promoter sequence-specific DNA binding; IEA:Ensembl. DR GO; GO:0000981; F:RNA polymerase II transcription factor activity, sequence-specific DNA binding; IBA:GO_Central. DR GO; GO:0003700; F:transcription factor activity, sequence-specific DNA binding; NAS:ProtInc. DR GO; GO:0001077; F:transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding; IEA:Ensembl. DR GO; GO:0030509; P:BMP signaling pathway; ISS:BHF-UCL. DR GO; GO:0048469; P:cell maturation; IEA:Ensembl. DR GO; GO:0071773; P:cellular response to BMP stimulus; ISS:BHF-UCL. DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; IEA:Ensembl. DR GO; GO:0002063; P:chondrocyte development; IEA:Ensembl. DR GO; GO:0002062; P:chondrocyte differentiation; IBA:GO_Central. DR GO; GO:0048701; P:embryonic cranial skeleton morphogenesis; IEA:Ensembl. DR GO; GO:0035115; P:embryonic forelimb morphogenesis; IEA:Ensembl. DR GO; GO:0001958; P:endochondral ossification; IEA:Ensembl. DR GO; GO:0010467; P:gene expression; TAS:Reactome. DR GO; GO:0030097; P:hemopoiesis; IBA:GO_Central. DR GO; GO:0045879; P:negative regulation of smoothened signaling pathway; IEA:Ensembl. DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central. DR GO; GO:0042475; P:odontogenesis of dentin-containing tooth; IEA:Ensembl. DR GO; GO:0001503; P:ossification; TAS:UniProtKB. DR GO; GO:0002076; P:osteoblast development; IEA:Ensembl. DR GO; GO:0001649; P:osteoblast differentiation; IEP:UniProtKB. DR GO; GO:0002051; P:osteoblast fate commitment; IEA:Ensembl. DR GO; GO:0008284; P:positive regulation of cell proliferation; IEA:Ensembl. DR GO; GO:0032332; P:positive regulation of chondrocyte differentiation; IEA:Ensembl. DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IEA:Ensembl. DR GO; GO:1901522; P:positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus; ISS:BHF-UCL. DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB. DR GO; GO:0045595; P:regulation of cell differentiation; IBA:GO_Central. DR GO; GO:0040036; P:regulation of fibroblast growth factor receptor signaling pathway; IEA:Ensembl. DR GO; GO:0042487; P:regulation of odontogenesis of dentin-containing tooth; IEA:Ensembl. DR GO; GO:0006357; P:regulation of transcription from RNA polymerase II promoter; IBA:GO_Central. DR GO; GO:0048863; P:stem cell differentiation; IEA:Ensembl. DR GO; GO:0030217; P:T cell differentiation; IEA:Ensembl. DR GO; GO:0006367; P:transcription initiation from RNA polymerase II promoter; TAS:Reactome. DR Gene3D; 2.60.40.720; -; 1. DR Gene3D; 4.10.770.10; -; 1. DR InterPro; IPR000040; AML1_Runt. DR InterPro; IPR008967; p53-like_TF_DNA-bd. DR InterPro; IPR012346; p53/RUNT-type_TF_DNA-bd. DR InterPro; IPR013524; Runt_dom. DR InterPro; IPR027384; Runx_central_dom. DR InterPro; IPR013711; RunxI_C_dom. DR InterPro; IPR016554; TF_Runt-rel_RUNX. DR PANTHER; PTHR11950; PTHR11950; 2. DR Pfam; PF00853; Runt; 1. DR Pfam; PF08504; RunxI; 1. DR PIRSF; PIRSF009374; TF_Runt-rel_RUNX; 1. DR PRINTS; PR00967; ONCOGENEAML1. DR SUPFAM; SSF49417; SSF49417; 1. DR PROSITE; PS51062; RUNT; 1. PE 1: Evidence at protein level; KW Alternative splicing; Complete proteome; Disease mutation; KW DNA-binding; Nucleus; Phosphoprotein; Polymorphism; KW Reference proteome; Transcription; Transcription regulation. FT CHAIN 1 521 Runt-related transcription factor 2. FT /FTId=PRO_0000174659. FT DOMAIN 101 229 Runt. {ECO:0000255|PROSITE- FT ProRule:PRU00399}. FT REGION 242 258 Required for interaction with FOXO1. FT {ECO:0000250}. FT REGION 336 439 Interaction with KAT6A. {ECO:0000250}. FT REGION 374 468 Interaction with KAT6B. FT COMPBIAS 49 71 Poly-Gln. FT COMPBIAS 73 89 Poly-Ala. FT COMPBIAS 237 521 Pro/Ser/Thr-rich. FT MOD_RES 451 451 Phosphoserine; by CDK1. FT {ECO:0000269|PubMed:16407259}. FT VAR_SEQ 1 19 MASNSLFSTVTPCQQNFFW -> MRIPV (in isoform FT 2). {ECO:0000305}. FT /FTId=VSP_005937. FT VAR_SEQ 341 362 Missing (in isoform 3). FT {ECO:0000303|PubMed:9233771}. FT /FTId=VSP_005938. FT VARIANT 53 53 Q -> L (in CLCD). FT {ECO:0000269|PubMed:12081718}. FT /FTId=VAR_064081. FT VARIANT 78 83 Missing. {ECO:0000269|PubMed:9182765}. FT /FTId=VAR_012131. FT VARIANT 84 84 A -> AAAAAAAAAAA (in CLCD; the patient FT also shows brachydactyly of hands and FT feet). {ECO:0000269|PubMed:9182765}. FT /FTId=VAR_012130. FT VARIANT 113 113 L -> R (in CLCD). FT {ECO:0000269|PubMed:10521292}. FT /FTId=VAR_012132. FT VARIANT 118 118 S -> N (in CLCD). FT {ECO:0000269|PubMed:20648631}. FT /FTId=VAR_064082. FT VARIANT 118 118 S -> R (in CLCD). FT {ECO:0000269|PubMed:10521292}. FT /FTId=VAR_012133. FT VARIANT 121 121 F -> C (in CLCD). FT {ECO:0000269|PubMed:10521292}. FT /FTId=VAR_012134. FT VARIANT 123 123 C -> R (in CLCD). FT {ECO:0000269|PubMed:10521292}. FT /FTId=VAR_012135. FT VARIANT 131 131 R -> C (in CLCD). FT {ECO:0000269|PubMed:20648631}. FT /FTId=VAR_064083. FT VARIANT 131 131 R -> G (in CLCD). FT {ECO:0000269|PubMed:16270353}. FT /FTId=VAR_064084. FT VARIANT 131 131 R -> S (in CLCD). FT {ECO:0000269|PubMed:20648631}. FT /FTId=VAR_064085. FT VARIANT 133 133 Missing (in CLCD). FT {ECO:0000269|PubMed:10545612}. FT /FTId=VAR_012136. FT VARIANT 136 136 L -> P (in CLCD). FT {ECO:0000269|PubMed:20648631}. FT /FTId=VAR_064086. FT VARIANT 156 156 V -> D (in CLCD). FT {ECO:0000269|PubMed:20648631}. FT /FTId=VAR_064087. FT VARIANT 156 156 V -> G (in CLCD). FT {ECO:0000269|PubMed:11857736}. FT /FTId=VAR_064088. FT VARIANT 169 169 R -> P (in CLCD). FT {ECO:0000269|PubMed:11857736, FT ECO:0000269|PubMed:12424590}. FT /FTId=VAR_064089. FT VARIANT 169 169 R -> Q (in CLCD). FT {ECO:0000269|PubMed:10545612}. FT /FTId=VAR_012137. FT VARIANT 175 175 M -> K (in CLCD). FT {ECO:0000269|PubMed:20648631}. FT /FTId=VAR_064090. FT VARIANT 175 175 M -> R (in CLCD; abolishes DNA binding). FT {ECO:0000269|PubMed:10545612, FT ECO:0000269|PubMed:9207800}. FT /FTId=VAR_012138. FT VARIANT 175 175 M -> V (in CLCD). FT {ECO:0000269|PubMed:20648631}. FT /FTId=VAR_064091. FT VARIANT 187 187 F -> S (in CLCD). FT {ECO:0000269|PubMed:20648631}. FT /FTId=VAR_064092. FT VARIANT 190 190 R -> Q (in CLCD; abolishes DNA binding). FT {ECO:0000269|PubMed:10545612}. FT /FTId=VAR_012139. FT VARIANT 190 190 R -> W (in CLCD; has severely impaired FT DNA binding and transactivation). FT {ECO:0000269|PubMed:10980549, FT ECO:0000269|PubMed:11857736, FT ECO:0000269|PubMed:12196916}. FT /FTId=VAR_012140. FT VARIANT 191 191 S -> N (in CLCD; abolishes DNA binding). FT {ECO:0000269|PubMed:10545612, FT ECO:0000269|PubMed:9207800}. FT /FTId=VAR_012141. FT VARIANT 193 193 R -> C (in CLCD). FT {ECO:0000269|PubMed:10545612}. FT /FTId=VAR_012142. FT VARIANT 193 193 R -> Q (in CLCD). FT {ECO:0000269|PubMed:20648631}. FT /FTId=VAR_064093. FT VARIANT 197 197 F -> S (in CLCD; retains FT heterodimerization activity together with FT a trace potential for DNA binding; FT retains a low but still substantial FT transactivation activity). FT {ECO:0000269|PubMed:10689183, FT ECO:0000269|PubMed:12196916}. FT /FTId=VAR_012143. FT VARIANT 199 199 L -> F (in CLCD; abolishes DNA binding). FT {ECO:0000269|PubMed:10545612}. FT /FTId=VAR_012144. FT VARIANT 200 200 T -> A (in CLCD; mild; associated also FT with isolated dental anomalies; normal FT DNA binding). FT {ECO:0000269|PubMed:10545612}. FT /FTId=VAR_012145. FT VARIANT 200 200 T -> I (in CLCD). FT {ECO:0000269|PubMed:20648631}. FT /FTId=VAR_064094. FT VARIANT 201 201 I -> K (in CLCD). FT {ECO:0000269|PubMed:11857736}. FT /FTId=VAR_064095. FT VARIANT 205 205 T -> R (in CLCD). FT {ECO:0000269|PubMed:10521292}. FT /FTId=VAR_012146. FT VARIANT 209 209 Q -> H (in CLCD). FT {ECO:0000269|PubMed:20648631}. FT /FTId=VAR_064096. FT VARIANT 209 209 Q -> R (in CLCD). FT {ECO:0000269|PubMed:10545612}. FT /FTId=VAR_012147. FT VARIANT 211 211 A -> P (in CLCD). FT {ECO:0000269|PubMed:20648631}. FT /FTId=VAR_064097. FT VARIANT 218 218 K -> E (in CLCD). FT {ECO:0000269|PubMed:20648631}. FT /FTId=VAR_064098. FT VARIANT 218 218 K -> N (in CLCD; has severely impaired FT DNA binding and transactivation). FT {ECO:0000269|PubMed:12196916}. FT /FTId=VAR_064099. FT VARIANT 218 218 K -> Q (in CLCD). FT {ECO:0000269|PubMed:20648631}. FT /FTId=VAR_064100. FT VARIANT 220 220 T -> I (in CLCD; has severely impaired FT DNA binding and transactivation). FT {ECO:0000269|PubMed:12196916}. FT /FTId=VAR_064101. FT VARIANT 225 225 R -> L (in CLCD). FT {ECO:0000269|PubMed:20648631}. FT /FTId=VAR_064102. FT VARIANT 225 225 R -> Q (in CLCD; interferes with nuclear FT localization; abolishes DNA binding). FT {ECO:0000269|PubMed:10521292, FT ECO:0000269|PubMed:10545612, FT ECO:0000269|PubMed:11857736, FT ECO:0000269|PubMed:12196916, FT ECO:0000269|PubMed:16270353}. FT /FTId=VAR_012148. FT VARIANT 225 225 R -> W (in CLCD; interferes with nuclear FT localization; has severely impaired DNA FT binding and transactivation). FT {ECO:0000269|PubMed:10521292, FT ECO:0000269|PubMed:11857736, FT ECO:0000269|PubMed:12196916, FT ECO:0000269|PubMed:19744171}. FT /FTId=VAR_012149. FT VARIANT 228 228 R -> G (in CLCD). FT {ECO:0000269|PubMed:20648631}. FT /FTId=VAR_064103. FT VARIANT 233 233 K -> R (in CLCD). FT {ECO:0000269|PubMed:20648631}. FT /FTId=VAR_064104. FT VARIANT 287 287 D -> N (in CLCD). FT {ECO:0000269|PubMed:20648631}. FT /FTId=VAR_064105. FT VARIANT 362 362 A -> V (in CLCD). FT {ECO:0000269|PubMed:11857736}. FT /FTId=VAR_064106. FT VARIANT 420 420 T -> I (in CLCD). FT {ECO:0000269|PubMed:20082269}. FT /FTId=VAR_064107. FT VARIANT 420 420 T -> N (in CLCD). FT {ECO:0000269|PubMed:20648631}. FT /FTId=VAR_064108. FT VARIANT 511 511 G -> S (in CLCD; unknown pathological FT significance; dbSNP:rs11498198). FT {ECO:0000269|PubMed:10521292}. FT /FTId=VAR_012150. FT MUTAGEN 451 451 S->A: Reduced DNA-binding and impaired FT phosphorylation. FT {ECO:0000269|PubMed:16407259}. FT CONFLICT 16 16 N -> S (in Ref. 4; AAC77441). FT {ECO:0000305}. SQ SEQUENCE 521 AA; 56648 MW; 44C4F3867D6F3EB1 CRC64; MASNSLFSTV TPCQQNFFWD PSTSRRFSPP SSSLQPGKMS DVSPVVAAQQ QQQQQQQQQQ QQQQQQQQQQ QEAAAAAAAA AAAAAAAAAV PRLRPPHDNR TMVEIIADHP AELVRTDSPN FLCSVLPSHW RCNKTLPVAF KVVALGEVPD GTVVTVMAGN DENYSAELRN ASAVMKNQVA RFNDLRFVGR SGRGKSFTLT ITVFTNPPQV ATYHRAIKVT VDGPREPRRH RQKLDDSKPS LFSDRLSDLG RIPHPSMRVG VPPQNPRPSL NSAPSPFNPQ GQSQITDPRQ AQSSPPWSYD QSYPSYLSQM TSPSIHSTTP LSSTRGTGLP AITDVPRRIS DDDTATSDFC LWPSTLSKKS QAGASELGPF SDPRQFPSIS SLTESRFSNP RMHYPATFTY TPPVTSGMSL GMSATTHYHT YLPPPYPGSS QSQSGPFQTS STPYLYYGTS SGSYQFPMVP GGDRSPSRML PPCTTTSNGS TLLNPNLPNQ NDGVDADGSH SSSPTVLNSS GRMDESVWRP Y //