Protein-coding gene in the species Homo sapiens
MAD protein is aprotein that in humans is encoded by theMXD1 gene .[ 5] [ 6]
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.[ 6]
MXD1 has been shown tointeract withHistone deacetylase 2 ,[ 7] [ 8] SMC3 ,[ 9] MLX ,[ 10] [ 11] SIN3A [ 12] [ 13] [ 14] andMAX .[ 9] [ 15] [ 16] [ 17]
^a b c GRCh38: Ensembl release 89: ENSG00000059728 –Ensembl , May 2017^a b c GRCm38: Ensembl release 89: ENSMUSG00000001156 –Ensembl , May 2017^ "Human PubMed Reference:" .National Center for Biotechnology Information, U.S. National Library of Medicine .^ "Mouse PubMed Reference:" .National Center for Biotechnology Information, U.S. National Library of Medicine .^ 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 . ^a b "Entrez Gene: MXD1 MAX dimerization protein 1" .^ 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 .89 (3). UNITED STATES:349– 56.doi :10.1016/S0092-8674(00)80215-9 .ISSN 0092-8674 .PMID 9150134 .S2CID 13490886 . ^ 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 .7 (12). UNITED STATES:1100– 4.doi :10.1038/81944 .hdl :2066/79474 .ISSN 1072-8368 .PMID 11101889 .S2CID 12451972 . ^a b 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 .16 (9). ENGLAND:1149– 59.doi :10.1038/sj.onc.1201634 .ISSN 0950-9232 .PMID 9528857 . ^ 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 .10 (6). England:617– 27.doi :10.1093/hmg/10.6.617 .ISSN 0964-6906 .PMID 11230181 . ^ 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 .19 (29). ENGLAND:3266– 77.doi :10.1038/sj.onc.1203634 .ISSN 0950-9232 .PMID 10918583 . ^ 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 .11 (8). United States:738– 46.doi :10.1038/nsmb798 .ISSN 1545-9993 .PMID 15235594 .S2CID 44324333 . ^ 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 .103 (4). UNITED STATES:655– 65.doi :10.1016/S0092-8674(00)00168-9 .ISSN 0092-8674 .PMID 11106735 .S2CID 17476603 . ^ 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 .80 (5). UNITED STATES:767– 76.doi :10.1016/0092-8674(95)90355-0 .ISSN 0092-8674 .PMID 7889570 .S2CID 8749951 . ^ 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. 99 (22). United States:14189– 94.Bibcode :2002PNAS...9914189L .doi :10.1073/pnas.232310199 .ISSN 0027-8424 .PMC 137859 .PMID 12391307 . ^ Ayer, D E; Kretzner L; Eisenman R N (January 1993). "Mad: a heterodimeric partner for Max that antagonizes Myc transcriptional activity".Cell .72 (2). UNITED STATES:211– 22.doi :10.1016/0092-8674(93)90661-9 .ISSN 0092-8674 .PMID 8425218 .S2CID 13317223 . ^ 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 .112 (2). United States:193– 205.doi :10.1016/S0092-8674(02)01284-9 .ISSN 0092-8674 .PMID 12553908 .S2CID 16142388 . 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 .S2CID 8749951 . 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 .S2CID 13317223 . 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 .S2CID 14233219 . 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 .S2CID 13490886 . 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.Bibcode :2002PNAS...9916899M .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 .S2CID 16142388 . 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.Bibcode :2005Natur.434..724H .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 . Overview of all the structural information available in thePDB forUniProt :Q05195 (Max dimerization protein 1) at thePDBe-KB .
(1) Basic domains
(1.1) Basic leucine zipper (bZIP )(1.2) Basic helix-loop-helix (bHLH )
Group A Group B Group C bHLH-PAS Group D Group E Group F bHLH-COE
(1.3) bHLH-ZIP (1.4) NF-1 (1.5) RF-X (1.6) Basic helix-span-helix (bHSH)
(2.1) Nuclear receptor (Cys4 )
subfamily 1 subfamily 2 subfamily 3 subfamily 4 subfamily 5 subfamily 6 subfamily 0
(2.2) Other Cys4 (2.3) Cys2 His2 (2.4) Cys6 (2.5) Alternating composition (2.6) WRKY
(4)β-Scaffold factors with minor groove contacts
(0) Other transcription factors