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Gene Review

MAX  -  MYC associated factor X

Homo sapiens

Synonyms: BHLHD4, Class D basic helix-loop-helix protein 4, Myc-associated factor X, Protein max, bHLHd4, ...
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Disease relevance of MAX

  • Detectable levels of MAX messenger RNA were found in a set of human neuroblastoma tumors and established cell lines [1].
  • Fitness as measured by VO2 MAX increased in both control (33.8 +/- 1.7 to 43.2 +/- 3.5 ml/min/kg) and diabetic (38.7 +/- 3.3 to 46.5 +/- 3.6 ml/min/kg) (P less than 0.05) subjects although body weight remained unchanged [2].
  • Neither the fall in maximal QT nor rise in [Hb] with chronic hypoxia therefore appear to affect VO2 MAX [3].
  • The performance of the OIA MAX test did not depend on the severity of pharyngitis [4].
  • Only during allograft rejection were infiltrating macrophages found to express MAX antigens but not at sites of "non-specific" inflammation or granuloma formation [5].

Psychiatry related information on MAX


High impact information on MAX

  • The nucleotide sequence of L1 elements includes an A-rich 3' end and two long open reading frames (orf-1 and orf-2), the second of which encodes a potential polypeptide having sequence homology with the reverse transcriptases [7].
  • The USF b/HLH cocrystal structure resembles the structure of the b/HLH/Z domain of the homologous protein Max and reveals (i) that the truncated, b/HLH DNA binding domain homodimerizes, forming a parallel, left-handed four-helix bundle, and (ii) that the basic region becomes alpha-helical on binding to the major groove of the DNA sequence CACGTG [8].
  • Third, we found that an allele of SNP4 (rs4950928), the tagging SNP of CCC, impaired the MYC/MAX-regulated transcriptional activation of CHI3L1 by altering the transcriptional-factor consensus sequences, and this may be responsible for the decreased expression of the CCC haplotype [9].
  • MNT, a MAX-binding antagonist of c-MYC function, was up-regulated, implying a negative feedback loop [10].
  • The MAX 1-26-termed markers failed to increase on EDMs, in contrast to plastic-cultured monocytes [11].

Chemical compound and disease context of MAX


Biological context of MAX


Anatomical context of MAX

  • Hemizygosity of the MAX gene locus in HL60 cells [18].
  • M phi matured in vivo and isolated from body fluids were positive with some but not all MAX mAbs [19].
  • NGF-beta protein levels were low in normal chondrocytes, increased in MIN osteoarthritic cartilage and further enhanced in MAX osteoarthritic cartilage [20].
  • Articular cartilage was split into two zones showing macroscopically and histologically the lowest (MIN) and highest (MAX) degree of osteoarthritic damage [20].
  • The diagnostic value of the band count as an indicator for ID was evaluated in comparison to the WBC count, the neutrophil count, and the left-shift indicators of two automated hematologic analyzers, H*1 Technicon (Bayer Technicon Instruments, Tarrytown, NY) and Coulter MAX M (Coulter Electronics, Hialeah, Fla) [21].

Associations of MAX with chemical compounds

  • Plasma glucose increased from similar resting values to a peak in the early recovery period at 7.2 +/- 0.44 in MAX and 6.8 +/- 0.37 in P, but only 5.2 +/- 0.3 mmol/L in C [22].
  • To clarify the effects of multivitamin supplements, several large randomized clinical trials are underway, including the Physicians' Health Study II, the Selenium and Vitamin E Cancer Prevention Trial, and a European study, Suppl??mentation en Vitamines et Min??raux Antioxydants (SU.VI. MAX) [23].
  • Furthermore, a novel dual-step SPE procedure was developed for the pre-concentration and purification of cytokinin nucleotides using Oasis HLB and Oasis MAX cartridges [24].
  • The phenols adsorbed on Oasis MAX as phenolate ions were desorbed after derivatization with pentafluoropyridine [25].
  • Fourteen phenols including chlorophenols and alkylphenols, could be efficiently adsorbed on a strong anion-exchange solid phase, Oasis MAX [25].

Physical interactions of MAX

  • The protein Max binds to c-Myc and the heterodimer c-Myc/Max seems to be the active form in vivo [26].
  • The MYC/MAX complexes transactivate a number of MYC-target genes in a sequence-specific manner [17].
  • Repression of transcription at the human T-cell receptor Vbeta2.2 segment is mediated by a MAX/MAD/mSin3 complex acting as a scaffold for HDAC activity [27].

Other interactions of MAX

  • We further demonstrate that the heterodimeric partner of c-MYC, MAX, interacts with a different MMR protein, MSH2, both in vitro and in vivo [28].
  • MYCN is a member of the myc family of proto-oncogenes which encode nuclear proteins that form heterodimers with MAX protein through their conserved HLHZip domains [17].
  • This region contains a CAAT motif sequence and consensus binding sites for Sp1, heat-shock factor, and MYC-MAX, which are conserved in the rabbit FKBP4 promoter and, when deleted, dramatically reduced promoter activity in T-47D cells [29].
  • Analysis by reverse transcriptase polymerase chain reaction and hybridization to specific oligodeoxynucleotide probes revealed approximately equal amounts of two MAX transcripts in all cases analyzed [1].
  • IL-10 protein intracellular levels were significantly higher in MAX than in MIN osteoarthritic cartilage or in healthy cartilage [30].

Analytical, diagnostic and therapeutic context of MAX

  • Immunoprecipitations with a specific antibody to MAX detected two proteins of M(r) 21,000 and 22,000 in approximately equal amounts in all neuroblastoma lines regardless of N-myc amplification and/or expression [1].
  • We have now found, by fluorescence in situ hybridization and quantified Southern blot analyses, that the MAX gene has been reduced to hemizygosity in HL60 cells [18].
  • Using fairly simple statistics we have written algorithms for estimating the diversity in libraries generated by the most commonly used protocols, including error-prone PCR, DNA shuffling, StEP PCR, oligonucleotide-directed randomization, MAX randomization, synthetic shuffling, DHR, ADO and SISDC [31].
  • At maximum, treadmill running resulted in a lower SaO2 (88.6+/-2% versus 92.6+/-2.0%) a lower ventilatory equivalent for carbon dioxide (VE/VCO2; 28.8+/-0.6 versus 31.2+/-0.9), and a higher maximal oxygen consumption (VO2, MAX; 4.83+/-0.11 l x min(-1) versus 4.61+/-0.14 l x min(-1) when compared to cycle ergometry [32].
  • The equation F=F MAX-P TIP/R was used to graph flow values (F) from the maximum measured flow (F MAX), the calculated resistance to air flow offered by the colonoscope (R), and the air pressure observed at the colonoscope tip (P TIP ) [33].


  1. Lack of correlation between N-myc and MAX expression in neuroblastoma tumors and in cell lines: implication for N-myc-MAX complex formation. Raschella, G., Romeo, A., Negroni, A., Pucci, S., Dominici, C., Castello, M.A., Bevilacqua, P., Felsani, A., Calabretta, B. Cancer Res. (1994) [Pubmed]
  2. Comparison of the acute and long-term effects of exercise on glucose control in type I diabetes. Zinman, B., Zuniga-Guajardo, S., Kelly, D. Diabetes Care (1984) [Pubmed]
  3. A theoretical analysis of factors determining VO2 MAX at sea level and altitude. Wagner, P.D. Respiration physiology. (1996) [Pubmed]
  4. Effect of using 2 throat swabs vs 1 throat swab on detection of group A streptococcus by a rapid antigen detection test. Ezike, E.N., Rongkavilit, C., Fairfax, M.R., Thomas, R.L., Asmar, B.I. Archives of pediatrics & adolescent medicine. (2005) [Pubmed]
  5. Human macrophage maturation and heterogeneity: restricted expression of late differentiation antigens in situ. Andreesen, R., Gadd, S., Costabel, U., Leser, H.G., Speth, V., Cesnik, B., Atkins, R.C. Cell Tissue Res. (1988) [Pubmed]
  6. Noise-induced hearing loss: a possible marker for high blood pressure in older noise-exposed populations. Talbott, E.O., Findlay, R.C., Kuller, L.H., Lenkner, L.A., Matthews, K.A., Day, R.D., Ishii, E.K. Journal of occupational medicine. : official publication of the Industrial Medical Association. (1990) [Pubmed]
  7. Haemophilia A resulting from de novo insertion of L1 sequences represents a novel mechanism for mutation in man. Kazazian, H.H., Wong, C., Youssoufian, H., Scott, A.F., Phillips, D.G., Antonarakis, S.E. Nature (1988) [Pubmed]
  8. Structure and function of the b/HLH/Z domain of USF. Ferré-D'Amaré, A.R., Pognonec, P., Roeder, R.G., Burley, S.K. EMBO J. (1994) [Pubmed]
  9. Functional Variants in the Promoter Region of Chitinase 3-Like 1 (CHI3L1) and Susceptibility to Schizophrenia. Zhao, X., Tang, R., Gao, B., Shi, Y., Zhou, J., Guo, S., Zhang, J., Wang, Y., Tang, W., Meng, J., Li, S., Wang, H., Ma, G., Lin, C., Xiao, Y., Feng, G., Lin, Z., Zhu, S., Xing, Y., Sang, H., St Clair, D., He, L. Am. J. Hum. Genet. (2007) [Pubmed]
  10. Characterization of the c-MYC-regulated transcriptome by SAGE: identification and analysis of c-MYC target genes. Menssen, A., Hermeking, H. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  11. Monocyte long-term cultivation on microvascular endothelial cell monolayers: morphologic and phenotypic characterization and comparison with monocytes cultured on tissue culture plastic. Schumann, R.R., van der Bosch, J., Rüller, S., Ernst, M., Schlaak, M. Blood (1989) [Pubmed]
  12. Cloning, sequencing and mutagenesis of the genes for aromatic amine dehydrogenase from Alcaligenes faecalis and evolution of amine dehydrogenases. Chistoserdov, A.Y. Microbiology (Reading, Engl.) (2001) [Pubmed]
  13. The small MbtH-like protein encoded by an internal gene of the balhimycin biosynthetic gene cluster is not required for glycopeptide production. Stegmann, E., Rausch, C., Stockert, S., Burkert, D., Wohlleben, W. FEMS Microbiol. Lett. (2006) [Pubmed]
  14. Sequential expression of the MAD family of transcriptional repressors during differentiation and development. Quéva, C., Hurlin, P.J., Foley, K.P., Eisenman, R.N. Oncogene (1998) [Pubmed]
  15. Mapping of MAX to human chromosome 14 and mouse chromosome 12 by in situ hybridization. Gilladoga, A.D., Edelhoff, S., Blackwood, E.M., Eisenman, R.N., Disteche, C.M. Oncogene (1992) [Pubmed]
  16. Commonly occurring loss and mutation of the MXI1 gene in prostate cancer. Prochownik, E.V., Eagle Grove, L., Deubler, D., Zhu, X.L., Stephenson, R.A., Rohr, L.R., Yin, X., Brothman, A.R. Genes Chromosomes Cancer (1998) [Pubmed]
  17. The MYCN oncoprotein as a drug development target. Lu, X., Pearson, A., Lunec, J. Cancer Lett. (2003) [Pubmed]
  18. Hemizygosity of the MAX gene locus in HL60 cells. Ryan, K.M., al-Mulla, F., Jamieson, T., Birnie, G.D. Cancer Genet. Cytogenet. (1998) [Pubmed]
  19. Human macrophage maturation and heterogeneity: analysis with a newly generated set of monoclonal antibodies to differentiation antigens. Andreesen, R., Bross, K.J., Osterholz, J., Emmrich, F. Blood (1986) [Pubmed]
  20. Increased expression of nerve growth factor (NGF) and high affinity NGF receptor (p140 TrkA) in human osteoarthritic chondrocytes. Iannone, F., De Bari, C., Dell'Accio, F., Covelli, M., Patella, V., Lo Bianco, G., Lapadula, G. Rheumatology (Oxford, England) (2002) [Pubmed]
  21. The diagnostic value of the neutrophil left shift in predicting inflammatory and infectious disease. Seebach, J.D., Morant, R., Rüegg, R., Seifert, B., Fehr, J. Am. J. Clin. Pathol. (1997) [Pubmed]
  22. Glucoregulation during and after intense exercise: effects of beta-blockade. Sigal, R.J., Purdon, C., Bilinski, D., Vranic, M., Halter, J.B., Marliss, E.B. J. Clin. Endocrinol. Metab. (1994) [Pubmed]
  23. Clinical trials of vitamin and mineral supplements for cancer prevention. Greenwald, P., Anderson, D., Nelson, S.A., Taylor, P.R. Am. J. Clin. Nutr. (2007) [Pubmed]
  24. Analysis of cytokinin nucleotides in coconut (Cocos nucifera L.) water using capillary zone electrophoresis-tandem mass spectrometry after solid-phase extraction. Ge, L., Yong, J.W., Tan, S.N., Yang, X.H., Ong, E.S. Journal of chromatography. A. (2006) [Pubmed]
  25. High performance solid-phase analytical derivatization of phenols for gas chromatography-mass spectrometry. Kojima, M., Tsunoi, S., Tanaka, M. Journal of chromatography. A. (2004) [Pubmed]
  26. Differential regulation of Max and role of c-Myc during erythroid and myelomonocytic differentiation of K562 cells. Delgado, M.D., Lerga, A., Cañelles, M., Gómez-Casares, M.T., León, J. Oncogene (1995) [Pubmed]
  27. Repression of transcription at the human T-cell receptor Vbeta2.2 segment is mediated by a MAX/MAD/mSin3 complex acting as a scaffold for HDAC activity. Font, M.P., Cubizolles, M., Dombret, H., Cazes, L., Brenac, V., Sigaux, F., Buckle, M. Biochem. Biophys. Res. Commun. (2004) [Pubmed]
  28. Interactions of the DNA mismatch repair proteins MLH1 and MSH2 with c-MYC and MAX. Mac Partlin, M., Homer, E., Robinson, H., McCormick, C.J., Crouch, D.H., Durant, S.T., Matheson, E.C., Hall, A.G., Gillespie, D.A., Brown, R. Oncogene (2003) [Pubmed]
  29. Organization of the human FK506-binding immunophilin FKBP52 protein gene (FKBP4). Scammell, J.G., Hubler, T.R., Denny, W.B., Valentine, D.L. Genomics (2003) [Pubmed]
  30. Interleukin-10 and interleukin-10 receptor in human osteoarthritic and healthy chondrocytes. Iannone, F., De Bari, C., Dell'Accio, F., Covelli, M., Cantatore, F.P., Patella, V., Lo Bianco, G., Lapadula, G. Clinical and experimental rheumatology. (2001) [Pubmed]
  31. Statistics of protein library construction. Firth, A.E., Patrick, W.M. Bioinformatics (2005) [Pubmed]
  32. The effect of exercise modality on exercise-induced hypoxemia. Gavin, T.P., Stager, J.M. Respiration physiology. (1999) [Pubmed]
  33. A retrospective analysis of cecal barotrauma caused by colonoscope air flow and pressure. Woltjen, J.A. Gastrointest. Endosc. (2005) [Pubmed]
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