Runt-related transcription factor 2

Details

Name
Runt-related transcription factor 2
Synonyms
  • Acute myeloid leukemia 3 protein
  • AML3
  • CBF-alpha-1
  • CBFA1
  • Core-binding factor subunit alpha-1
  • Oncogene AML-3
  • OSF-2
  • OSF2
  • Osteoblast-specific transcription factor 2
  • PEA2-alpha A
  • PEBP2-alpha A
  • PEBP2A
  • Polyomavirus enhancer-binding protein 2 alpha A subunit
  • SL3-3 enhancer factor 1 alpha A subunit
  • SL3/AKV core-binding factor alpha A subunit
Gene Name
RUNX2
Organism
Humans
Amino acid sequence
>lcl|BSEQ0052620|Runt-related transcription factor 2
MASNSLFSTVTPCQQNFFWDPSTSRRFSPPSSSLQPGKMSDVSPVVAAQQQQQQQQQQQQ
QQQQQQQQQQQEAAAAAAAAAAAAAAAAAVPRLRPPHDNRTMVEIIADHPAELVRTDSPN
FLCSVLPSHWRCNKTLPVAFKVVALGEVPDGTVVTVMAGNDENYSAELRNASAVMKNQVA
RFNDLRFVGRSGRGKSFTLTITVFTNPPQVATYHRAIKVTVDGPREPRRHRQKLDDSKPS
LFSDRLSDLGRIPHPSMRVGVPPQNPRPSLNSAPSPFNPQGQSQITDPRQAQSSPPWSYD
QSYPSYLSQMTSPSIHSTTPLSSTRGTGLPAITDVPRRISDDDTATSDFCLWPSTLSKKS
QAGASELGPFSDPRQFPSISSLTESRFSNPRMHYPATFTYTPPVTSGMSLGMSATTHYHT
YLPPPYPGSSQSQSGPFQTSSTPYLYYGTSSGSYQFPMVPGGDRSPSRMLPPCTTTSNGS
TLLNPNLPNQNDGVDADGSHSSSPTVLNSSGRMDESVWRPY
Number of residues
521
Molecular Weight
56647.37
Theoretical pI
Not Available
GO Classification
Functions
ATP binding / DNA-binding transcription factor activity / DNA-binding transcription factor activity, RNA polymerase II-specific / RNA polymerase II cis-regulatory region sequence-specific DNA binding / sequence-specific double-stranded DNA binding
Processes
BMP signaling pathway / cellular response to BMP stimulus / chondrocyte differentiation / hemopoiesis / negative regulation of transcription, DNA-templated / neuron differentiation / ossification / osteoblast differentiation / positive regulation of osteoblast differentiation / positive regulation of transcription by RNA polymerase II / positive regulation of transcription from RNA polymerase II promoter involved in cellular response to chemical stimulus / positive regulation of transcription, DNA-templated / regulation of cell differentiation / regulation of transcription by RNA polymerase II / regulation of transcription initiation from RNA polymerase II promoter
Components
chromatin / cytosol / nucleoplasm / nucleus
General Function
Transcription factor involved in osteoblastic differentiation and skeletal morphogenesis (PubMed:28505335, PubMed:28738062, PubMed:28703881). 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.
Specific Function
Atp binding
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Nucleus
Gene sequence
>lcl|BSEQ0052621|Runt-related transcription factor 2 (RUNX2)
ATGGCATCAAACAGCCTCTTCAGCACAGTGACACCATGTCAGCAAAACTTCTTTTGGGAT
CCGAGCACCAGCCGGCGCTTCAGCCCCCCCTCCAGCAGCCTGCAGCCCGGCAAAATGAGC
GACGTGAGCCCGGTGGTGGCTGCGCAACAGCAGCAGCAACAGCAGCAGCAGCAACAGCAG
CAGCAGCAGCAGCAACAGCAGCAGCAGCAGCAGGAGGCGGCGGCGGCGGCTGCGGCGGCG
GCGGCGGCTGCGGCGGCGGCAGCTGCAGTGCCCCGGTTGCGGCCGCCCCACGACAACCGC
ACCATGGTGGAGATCATCGCCGACCACCCGGCCGAACTCGTCCGCACCGACAGCCCCAAC
TTCCTGTGCTCGGTGCTGCCCTCGCACTGGCGCTGCAACAAGACCCTGCCCGTGGCCTTC
AAGGTGGTAGCCCTCGGAGAGGTACCAGATGGGACTGTGGTTACTGTCATGGCGGGTAAC
GATGAAAATTATTCTGCTGAGCTCCGGAATGCCTCTGCTGTTATGAAAAACCAAGTAGCA
AGGTTCAACGATCTGAGATTTGTGGGCCGGAGTGGACGAGGCAAGAGTTTCACCTTGACC
ATAACCGTCTTCACAAATCCTCCCCAAGTAGCTACCTATCACAGAGCAATTAAAGTTACA
GTAGATGGACCTCGGGAACCCAGAAGGCACAGACAGAAGCTTGATGACTCTAAACCTAGT
TTGTTCTCTGACCGCCTCAGTGATTTAGGGCGCATTCCTCATCCCAGTATGAGAGTAGGT
GTCCCGCCTCAGAACCCACGGCCCTCCCTGAACTCTGCACCAAGTCCTTTTAATCCACAA
GGACAGAGTCAGATTACAGACCCCAGGCAGGCACAGTCTTCCCCGCCGTGGTCCTATGAC
CAGTCTTACCCCTCCTACCTGAGCCAGATGACGTCCCCGTCCATCCACTCTACCACCCCG
CTGTCTTCCACACGGGGCACTGGGCTTCCTGCCATCACCGATGTGCCTAGGCGCATTTCA
GATGATGACACTGCCACCTCTGACTTCTGCCTCTGGCCTTCCACTCTCAGTAAGAAGAGC
CAGGCAGGTGCTTCAGAACTGGGCCCTTTTTCAGACCCCAGGCAGTTCCCAAGCATTTCA
TCCCTCACTGAGAGCCGCTTCTCCAACCCACGAATGCACTATCCAGCCACCTTTACTTAC
ACCCCGCCAGTCACCTCAGGCATGTCCCTCGGTATGTCCGCCACCACTCACTACCACACC
TACCTGCCACCACCCTACCCCGGCTCTTCCCAAAGCCAGAGTGGACCCTTCCAGACCAGC
AGCACTCCATATCTCTACTATGGCACTTCGTCAGGATCCTATCAGTTTCCCATGGTGCCG
GGGGGAGACCGGTCTCCTTCCAGAATGCTTCCGCCATGCACCACCACCTCGAATGGCAGC
ACGCTATTAAATCCAAATTTGCCTAACCAGAATGATGGTGTTGACGCTGATGGAAGCCAC
AGCAGTTCCCCAACTGTTTTGAATTCTAGTGGCAGAATGGATGAATCTGTTTGGCGACCA
TATTGA
Chromosome Location
6
Locus
6p21.1
External Identifiers
ResourceLink
UniProtKB IDQ13950
UniProtKB Entry NameRUNX2_HUMAN
HGNC IDHGNC:10472
General References
  1. Mundlos S, Otto F, Mundlos C, Mulliken JB, Aylsworth AS, Albright S, Lindhout D, Cole WG, Henn W, Knoll JH, Owen MJ, Mertelsmann R, Zabel BU, Olsen BR: Mutations involving the transcription factor CBFA1 cause cleidocranial dysplasia. Cell. 1997 May 30;89(5):773-9. doi: 10.1016/s0092-8674(00)80260-3. [Article]
  2. Geoffroy V, Corral DA, Zhou L, Lee B, Karsenty G: Genomic organization, expression of the human CBFA1 gene, and evidence for an alternative splicing event affecting protein function. Mamm Genome. 1998 Jan;9(1):54-7. doi: 10.1007/s003359900679. [Article]
  3. Mungall AJ, Palmer SA, Sims SK, Edwards CA, Ashurst JL, Wilming L, Jones MC, Horton R, Hunt SE, Scott CE, Gilbert JG, Clamp ME, Bethel G, Milne S, Ainscough R, Almeida JP, Ambrose KD, Andrews TD, Ashwell RI, Babbage AK, Bagguley CL, Bailey J, Banerjee R, Barker DJ, Barlow KF, Bates K, Beare DM, Beasley H, Beasley O, Bird CP, Blakey S, Bray-Allen S, Brook J, Brown AJ, Brown JY, Burford DC, Burrill W, Burton J, Carder C, Carter NP, Chapman JC, Clark SY, Clark G, Clee CM, Clegg S, Cobley V, Collier RE, Collins JE, Colman LK, Corby NR, Coville GJ, Culley KM, Dhami P, Davies J, Dunn M, Earthrowl ME, Ellington AE, Evans KA, Faulkner L, Francis MD, Frankish A, Frankland J, French L, Garner P, Garnett J, Ghori MJ, Gilby LM, Gillson CJ, Glithero RJ, Grafham DV, Grant M, Gribble S, Griffiths C, Griffiths M, Hall R, Halls KS, Hammond S, Harley JL, Hart EA, Heath PD, Heathcott R, Holmes SJ, Howden PJ, Howe KL, Howell GR, Huckle E, Humphray SJ, Humphries MD, Hunt AR, Johnson CM, Joy AA, Kay M, Keenan SJ, Kimberley AM, King A, Laird GK, Langford C, Lawlor S, Leongamornlert DA, Leversha M, Lloyd CR, Lloyd DM, Loveland JE, Lovell J, Martin S, Mashreghi-Mohammadi M, Maslen GL, Matthews L, McCann OT, McLaren SJ, McLay K, McMurray A, Moore MJ, Mullikin JC, Niblett D, Nickerson T, Novik KL, Oliver K, Overton-Larty EK, Parker A, Patel R, Pearce AV, Peck AI, Phillimore B, Phillips S, Plumb RW, Porter KM, Ramsey Y, Ranby SA, Rice CM, Ross MT, Searle SM, Sehra HK, Sheridan E, Skuce CD, Smith S, Smith M, Spraggon L, Squares SL, Steward CA, Sycamore N, Tamlyn-Hall G, Tester J, Theaker AJ, Thomas DW, Thorpe A, Tracey A, Tromans A, Tubby B, Wall M, Wallis JM, West AP, White SS, Whitehead SL, Whittaker H, Wild A, Willey DJ, Wilmer TE, Wood JM, Wray PW, Wyatt JC, Young L, Younger RM, Bentley DR, Coulson A, Durbin R, Hubbard T, Sulston JE, Dunham I, Rogers J, Beck S: The DNA sequence and analysis of human chromosome 6. Nature. 2003 Oct 23;425(6960):805-11. [Article]
  4. Xiao ZS, Thomas R, Hinson TK, Quarles LD: Genomic structure and isoform expression of the mouse, rat and human Cbfa1/Osf2 transcription factor. Gene. 1998 Jul 3;214(1-2):187-97. doi: 10.1016/s0378-1119(98)00227-3. [Article]
  5. Zhang YW, Bae SC, Takahashi E, Ito Y: The cDNA cloning of the transcripts of human PEBP2alphaA/CBFA1 mapped to 6p12.3-p21.1, the locus for cleidocranial dysplasia. Oncogene. 1997 Jul 17;15(3):367-71. doi: 10.1038/sj.onc.1201352. [Article]
  6. Willis DM, Loewy AP, Charlton-Kachigian N, Shao JS, Ornitz DM, Towler DA: Regulation of osteocalcin gene expression by a novel Ku antigen transcription factor complex. J Biol Chem. 2002 Oct 4;277(40):37280-91. doi: 10.1074/jbc.M206482200. Epub 2002 Jul 26. [Article]
  7. Pelletier N, Champagne N, Stifani S, Yang XJ: MOZ and MORF histone acetyltransferases interact with the Runt-domain transcription factor Runx2. Oncogene. 2002 Apr 18;21(17):2729-40. doi: 10.1038/sj.onc.1205367. [Article]
  8. Qiao M, Shapiro P, Fosbrink M, Rus H, Kumar R, Passaniti A: Cell cycle-dependent phosphorylation of the RUNX2 transcription factor by cdc2 regulates endothelial cell proliferation. J Biol Chem. 2006 Mar 17;281(11):7118-28. Epub 2006 Jan 9. [Article]
  9. Ono M, Yaguchi H, Ohkura N, Kitabayashi I, Nagamura Y, Nomura T, Miyachi Y, Tsukada T, Sakaguchi S: Foxp3 controls regulatory T-cell function by interacting with AML1/Runx1. Nature. 2007 Apr 5;446(7136):685-9. doi: 10.1038/nature05673. Epub 2007 Mar 21. [Article]
  10. Cantin GT, Yi W, Lu B, Park SK, Xu T, Lee JD, Yates JR 3rd: Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis. J Proteome Res. 2008 Mar;7(3):1346-51. doi: 10.1021/pr0705441. Epub 2008 Jan 26. [Article]
  11. Moffatt P, Ben Amor M, Glorieux FH, Roschger P, Klaushofer K, Schwartzentruber JA, Paterson AD, Hu P, Marshall C, Fahiminiya S, Majewski J, Beaulieu CL, Boycott KM, Rauch F: Metaphyseal dysplasia with maxillary hypoplasia and brachydactyly is caused by a duplication in RUNX2. Am J Hum Genet. 2013 Feb 7;92(2):252-8. doi: 10.1016/j.ajhg.2012.12.001. Epub 2013 Jan 3. [Article]
  12. Hendriks IA, Lyon D, Young C, Jensen LJ, Vertegaal AC, Nielsen ML: Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat Struct Mol Biol. 2017 Mar;24(3):325-336. doi: 10.1038/nsmb.3366. Epub 2017 Jan 23. [Article]
  13. Lee B, Thirunavukkarasu K, Zhou L, Pastore L, Baldini A, Hecht J, Geoffroy V, Ducy P, Karsenty G: Missense mutations abolishing DNA binding of the osteoblast-specific transcription factor OSF2/CBFA1 in cleidocranial dysplasia. Nat Genet. 1997 Jul;16(3):307-10. doi: 10.1038/ng0797-307. [Article]
  14. Quack I, Vonderstrass B, Stock M, Aylsworth AS, Becker A, Brueton L, Lee PJ, Majewski F, Mulliken JB, Suri M, Zenker M, Mundlos S, Otto F: Mutation analysis of core binding factor A1 in patients with cleidocranial dysplasia. Am J Hum Genet. 1999 Nov;65(5):1268-78. doi: 10.1086/302622. [Article]
  15. Zhou G, Chen Y, Zhou L, Thirunavukkarasu K, Hecht J, Chitayat D, Gelb BD, Pirinen S, Berry SA, Greenberg CR, Karsenty G, Lee B: CBFA1 mutation analysis and functional correlation with phenotypic variability in cleidocranial dysplasia. Hum Mol Genet. 1999 Nov;8(12):2311-6. doi: 10.1093/hmg/8.12.2311. [Article]
  16. Zhang YW, 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: PEBP2alphaA/CBFA1 mutations in Japanese cleidocranial dysplasia patients. Gene. 2000 Feb 22;244(1-2):21-8. doi: 10.1016/s0378-1119(99)00558-2. [Article]
  17. Giannotti A, Tessa A, Patrono C, Florio LD, Velardo M, Dionisi-Vici C, Bertini E, Santorelli FM: A novel CBFA1 mutation (R190W) in an Italian family with cleidocranial dysplasia. Hum Mutat. 2000 Sep;16(3):277. doi: 10.1002/1098-1004(200009)16:3<277::AID-HUMU25>3.0.CO;2-V. [Article]
  18. Yoshida T, Kanegane H, Osato M, Yanagida M, Miyawaki T, Ito Y, Shigesada K: Functional analysis of RUNX2 mutations in Japanese patients with cleidocranial dysplasia demonstrates novel genotype-phenotype correlations. Am J Hum Genet. 2002 Oct;71(4):724-38. doi: 10.1086/342717. Epub 2002 Aug 26. [Article]
  19. Machuca-Tzili L, Monroy-Jaramillo N, Gonzalez-del Angel A, Kofman-Alfaro S: New mutations in the CBFA1 gene in two Mexican patients with cleidocranial dysplasia. Clin Genet. 2002 May;61(5):349-53. doi: 10.1034/j.1399-0004.2002.610505.x. [Article]
  20. Morava E, Karteszi J, Weisenbach J, Caliebe A, Mundlos S, Mehes K: Cleidocranial dysplasia with decreased bone density and biochemical findings of hypophosphatasia. Eur J Pediatr. 2002 Nov;161(11):619-22. doi: 10.1007/s00431-002-0977-x. Epub 2002 Oct 9. [Article]
  21. Otto F, Kanegane H, Mundlos S: Mutations in the RUNX2 gene in patients with cleidocranial dysplasia. Hum Mutat. 2002 Mar;19(3):209-16. doi: 10.1002/humu.10043. [Article]
  22. Kim HJ, Nam SH, Kim HJ, Park HS, Ryoo HM, Kim SY, Cho TJ, Kim SG, Bae SC, Kim IS, Stein JL, van Wijnen AJ, Stein GS, Lian JB, Choi JY: Four novel RUNX2 mutations including a splice donor site result in the cleidocranial dysplasia phenotype. J Cell Physiol. 2006 Apr;207(1):114-22. doi: 10.1002/jcp.20552. [Article]
  23. Wang GX, Sun RP, Song FL: A novel RUNX2 mutation (T420I) in Chinese patients with cleidocranial dysplasia. Genet Mol Res. 2010 Jan 12;9(1):41-7. doi: 10.4238/vol9-1gmr685. [Article]
  24. Ott CE, Leschik G, Trotier F, Brueton L, Brunner HG, Brussel W, Guillen-Navarro E, Haase C, Kohlhase J, Kotzot D, Lane A, Lee-Kirsch MA, Morlot S, Simon ME, Steichen-Gersdorf E, Tegay DH, Peters H, Mundlos S, Klopocki E: Deletions of the RUNX2 gene are present in about 10% of individuals with cleidocranial dysplasia. Hum Mutat. 2010 Aug;31(8):E1587-93. doi: 10.1002/humu.21298. [Article]
  25. Ryoo HM, Kang HY, Lee SK, Lee KE, Kim JW: RUNX2 mutations in cleidocranial dysplasia patients. Oral Dis. 2010 Jan;16(1):55-60. doi: 10.1111/j.1601-0825.2009.01623.x. Epub 2009 Sep 8. [Article]
  26. Callea M, Bellacchio E, Di Stazio M, Fattori F, Bertini E, Yavuz I, Clarich G, Gunay A: A case of cleidocranial dysplasia with peculiar dental features: pathogenetic role of the RUNX2 mutation and long term follow-up. Oral Health Dent Manag. 2014 Jun;13(2):548-51. [Article]
  27. Jung YJ, Bae HS, Ryoo HM, Baek SH: A novel RUNX2 mutation in exon 8, G462X, in a patient with Cleidocranial Dysplasia. J Cell Biochem. 2018 Jan;119(1):1152-1162. doi: 10.1002/jcb.26283. Epub 2017 Aug 23. [Article]
  28. Zeng L, Wei J, Han D, Liu H, Liu Y, Zhao N, Sun S, Wang Y, Feng H: Functional analysis of novel RUNX2 mutations in cleidocranial dysplasia. Mutagenesis. 2017 Jul 1;32(4):437-443. doi: 10.1093/mutage/gex012. [Article]
  29. Zhang X, Liu Y, Wang X, Sun X, Zhang C, Zheng S: Analysis of novel RUNX2 mutations in Chinese patients with cleidocranial dysplasia. PLoS One. 2017 Jul 24;12(7):e0181653. doi: 10.1371/journal.pone.0181653. eCollection 2017. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails