MXD1

MAX dimerization protein 1
PDB rendering based on 1nlw.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1E91​, 1G1E​, 1NLW​, 1PD7​, 1S5Q​
Identifiers
Symbols	MXD1 ; BHLHC58; MAD; MAD1
External IDs	OMIM: 600021 MGI: 96908 HomoloGene: 1767 GeneCards: MXD1 Gene
Gene ontology Molecular function • RNA polymerase II core promoter proximal region sequence-specific DNA binding • transcriptional repressor activity, RNA polymerase II core promoter proximal region sequence-specific binding • transcription factor activity, sequence-specific DNA binding • transcription cofactor activity • transcription corepressor activity • protein binding • protein dimerization activity Cellular component • nucleus Biological process • negative regulation of transcription from RNA polymerase II promoter • transcription, DNA-templated • multicellular organismal development • cell proliferation Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4084	17119
Ensembl	ENSG00000059728	ENSMUSG00000001156
UniProt	Q05195	Q8K1Z8
RefSeq (mRNA)	NM_001202513	NM_010751
RefSeq (protein)	NP_001189442	NP_034881
Location (UCSC)	Chr 2: 69.9 – 69.94 Mb	Chr 6: 86.65 – 86.67 Mb
PubMed search

MAD protein is a protein that in humans is encoded by the MXD1 gene.^[1][2]

MAD-MAX dimerization protein belongs to a subfamily of MAX-interacting proteins. This protein competes with MYC for binding to MAX to form a sequence-specific DNA-binding complex, acts as a transcriptional repressor (while MYC appears to function as an activator) and is a candidate tumor suppressor.^[2] The MAD-MAX protein dimer may be a reference to the popular cult classic film Mad Max (1979).

Interactions

MXD1 has been shown to interact with Histone deacetylase 2,^[3][4] SMC3,^[5] MLX,^[6][7] SIN3A^[8][9][10] and MAX.^{[5][11][12][13]}

References

1. Shapiro DN, Valentine V, Eagle L, Yin X, Morris SW, Prochownik EV (February 1995). "Assignment of the human MAD and MXI1 genes to chromosomes 2p12-p13 and 10q24-q25". Genomics 23 (1): 282–5. doi:10.1006/geno.1994.1496. PMID 7829091.
2. "Entrez Gene: MXD1 MAX dimerization protein 1".
3. Laherty, C D; Yang W M; Sun J M; Davie J R; Seto E; Eisenman R N (May 1997). "Histone deacetylases associated with the mSin3 corepressor mediate mad transcriptional repression". Cell (UNITED STATES) 89 (3): 349–56. doi:10.1016/S0092-8674(00)80215-9. ISSN 0092-8674. PMID 9150134.
4. Spronk, C A; Tessari M; Kaan A M; Jansen J F; Vermeulen M; Stunnenberg H G; Vuister G W (December 2000). "The Mad1-Sin3B interaction involves a novel helical fold". Nat. Struct. Biol. (UNITED STATES) 7 (12): 1100–4. doi:10.1038/81944. ISSN 1072-8368. PMID 11101889.
5. Gupta, K; Anand G; Yin X; Grove L; Prochownik E V (March 1998). "Mmip1: a novel leucine zipper protein that reverses the suppressive effects of Mad family members on c-myc". Oncogene (ENGLAND) 16 (9): 1149–59. doi:10.1038/sj.onc.1201634. ISSN 0950-9232. PMID 9528857.
6. Cairo, S; Merla G; Urbinati F; Ballabio A; Reymond A (March 2001). "WBSCR14, a gene mapping to the Williams--Beuren syndrome deleted region, is a new member of the Mlx transcription factor network". Hum. Mol. Genet. (England) 10 (6): 617–27. doi:10.1093/hmg/10.6.617. ISSN 0964-6906. PMID 11230181.
7. Meroni, G; Cairo S; Merla G; Messali S; Brent R; Ballabio A; Reymond A (July 2000). "Mlx, a new Max-like bHLHZip family member: the center stage of a novel transcription factors regulatory pathway?". Oncogene (ENGLAND) 19 (29): 3266–77. doi:10.1038/sj.onc.1203634. ISSN 0950-9232. PMID 10918583.
8. Swanson, Kurt A; Knoepfler Paul S; Huang Kai; Kang Richard S; Cowley Shaun M; Laherty Carol D; Eisenman Robert N; Radhakrishnan Ishwar (August 2004). "HBP1 and Mad1 repressors bind the Sin3 corepressor PAH2 domain with opposite helical orientations". Nat. Struct. Mol. Biol. (United States) 11 (8): 738–46. doi:10.1038/nsmb798. ISSN 1545-9993. PMID 15235594.
9. Brubaker, K; Cowley S M; Huang K; Loo L; Yochum G S; Ayer D E; Eisenman R N; Radhakrishnan I (November 2000). "Solution structure of the interacting domains of the Mad-Sin3 complex: implications for recruitment of a chromatin-modifying complex". Cell (UNITED STATES) 103 (4): 655–65. doi:10.1016/S0092-8674(00)00168-9. ISSN 0092-8674. PMID 11106735.
10. Ayer, D E; Lawrence Q A; Eisenman R N (March 1995). "Mad-Max transcriptional repression is mediated by ternary complex formation with mammalian homologs of yeast repressor Sin3". Cell (UNITED STATES) 80 (5): 767–76. doi:10.1016/0092-8674(95)90355-0. ISSN 0092-8674. PMID 7889570.
11. Lee, Clement M; Onésime Djamila; Reddy C Damodara; Dhanasekaran N; Reddy E Premkumar (October 2002). "JLP: A scaffolding protein that tethers JNK/p38MAPK signaling modules and transcription factors". Proc. Natl. Acad. Sci. U.S.A. (United States) 99 (22): 14189–94. doi:10.1073/pnas.232310199. ISSN 0027-8424. PMC 137859. PMID 12391307.
12. Ayer, D E; Kretzner L; Eisenman R N (January 1993). "Mad: a heterodimeric partner for Max that antagonizes Myc transcriptional activity". Cell (UNITED STATES) 72 (2): 211–22. doi:10.1016/0092-8674(93)90661-9. ISSN 0092-8674. PMID 8425218.
13. Nair, Satish K; Burley Stephen K (January 2003). "X-ray structures of Myc-Max and Mad-Max recognizing DNA. Molecular bases of regulation by proto-oncogenic transcription factors". Cell (United States) 112 (2): 193–205. doi:10.1016/S0092-8674(02)01284-9. ISSN 0092-8674. PMID 12553908.

Further reading

• Grandori C, Cowley SM, James LP, Eisenman RN (2001). "The Myc/Max/Mad network and the transcriptional control of cell behavior.". Annu. Rev. Cell Dev. Biol. 16 (1): 653–99. doi:10.1146/annurev.cellbio.16.1.653. PMID 11031250.
• Lüscher B (2001). "Function and regulation of the transcription factors of the Myc/Max/Mad network.". Gene 277 (1-2): 1–14. doi:10.1016/S0378-1119(01)00697-7. PMID 11602341.
• Ayer DE, Lawrence QA, Eisenman RN (1995). "Mad-Max transcriptional repression is mediated by ternary complex formation with mammalian homologs of yeast repressor Sin3.". Cell 80 (5): 767–76. doi:10.1016/0092-8674(95)90355-0. PMID 7889570.
• Edelhoff S, Ayer DE, Zervos AS, et al. (1994). "Mapping of two genes encoding members of a distinct subfamily of MAX interacting proteins: MAD to human chromosome 2 and mouse chromosome 6, and MXI1 to human chromosome 10 and mouse chromosome 19.". Oncogene 9 (2): 665–8. PMID 8290278.
• Ayer DE, Kretzner L, Eisenman RN (1993). "Mad: a heterodimeric partner for Max that antagonizes Myc transcriptional activity.". Cell 72 (2): 211–22. doi:10.1016/0092-8674(93)90661-9. PMID 8425218.
• Hassig CA, Fleischer TC, Billin AN, et al. (1997). "Histone deacetylase activity is required for full transcriptional repression by mSin3A.". Cell 89 (3): 341–7. doi:10.1016/S0092-8674(00)80214-7. PMID 9150133.
• Laherty CD, Yang WM, Sun JM, et al. (1997). "Histone deacetylases associated with the mSin3 corepressor mediate mad transcriptional repression.". Cell 89 (3): 349–56. doi:10.1016/S0092-8674(00)80215-9. PMID 9150134.
• Gupta K, Anand G, Yin X, et al. (1998). "Mmip1: a novel leucine zipper protein that reverses the suppressive effects of Mad family members on c-myc.". Oncogene 16 (9): 1149–59. doi:10.1038/sj.onc.1201634. PMID 9528857.
• FitzGerald MJ, Arsura M, Bellas RE, et al. (1999). "Differential effects of the widely expressed dMax splice variant of Max on E-box vs initiator element-mediated regulation by c-Myc.". Oncogene 18 (15): 2489–98. doi:10.1038/sj.onc.1202611. PMID 10229200.
• Khan MM, Nomura T, Kim H, et al. (2001). "Role of PML and PML-RARalpha in Mad-mediated transcriptional repression.". Mol. Cell 7 (6): 1233–43. doi:10.1016/S1097-2765(01)00257-X. PMID 11430826.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Nikiforov MA, Popov N, Kotenko I, et al. (2003). "The Mad and Myc basic domains are functionally equivalent.". J. Biol. Chem. 278 (13): 11094–9. doi:10.1074/jbc.M212298200. PMID 12538578.
• Nair SK, Burley SK (2003). "X-ray structures of Myc-Max and Mad-Max recognizing DNA. Molecular bases of regulation by proto-oncogenic transcription factors.". Cell 112 (2): 193–205. doi:10.1016/S0092-8674(02)01284-9. PMID 12553908.
• Siegel PM, Shu W, Massagué J (2003). "Mad upregulation and Id2 repression accompany transforming growth factor (TGF)-beta-mediated epithelial cell growth suppression.". J. Biol. Chem. 278 (37): 35444–50. doi:10.1074/jbc.M301413200. PMID 12824180.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Hillier LW, Graves TA, Fulton RS, et al. (2005). "Generation and annotation of the DNA sequences of human chromosomes 2 and 4.". Nature 434 (7034): 724–31. doi:10.1038/nature03466. PMID 15815621.
• Zada AA, Pulikkan JA, Bararia D, et al. (2007). "Proteomic discovery of Max as a novel interacting partner of C/EBPalpha: a Myc/Max/Mad link.". Leukemia 20 (12): 2137–46. doi:10.1038/sj.leu.2404438. PMID 17082780.