MAX (gene)

MAX
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1AN2, 1HLO, 1NKP, 1NLW, 1R05
Identifiers
Aliases	MAX, bHLHd4, max, MYC associated factor X
External IDs	MGI: 96921 HomoloGene: 1786 GeneCards: MAX
Gene ontology Molecular function • DNA binding • sequence-specific DNA binding • protein dimerization activity • protein homodimerization activity • transcription factor activity, sequence-specific DNA binding • protein complex binding • transcription coactivator activity • transcription cofactor activity • transcription factor activity, RNA polymerase II core promoter sequence-specific • RNA polymerase II core promoter proximal region sequence-specific DNA binding • protein binding • protein heterodimerization activity Cellular component • PML body • cell projection • nucleoplasm • MLL1 complex • dendrite • cytoplasm • nucleus Biological process • neuron apoptotic process • regulation of transcription, DNA-templated • protein complex assembly • regulation of transcription from RNA polymerase II promoter • cellular response to starvation • transcription from RNA polymerase II promoter • negative regulation of gene expression • transcription, DNA-templated • response to insulin • cellular response to peptide hormone stimulus • retina development in camera-type eye • response to axon injury • response to organonitrogen compound Sources:Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	4149	17187
Ensembl	ENSG00000125952	ENSMUSG00000059436
UniProt	P61244 Q8TAX8	P28574
RefSeq (mRNA)	NM_001271068 NM_001271069 NM_002382 NM_145112 NM_145113 NM_145114 NM_145116 NM_197957 NM_001320415	NM_001146176 NM_008558
RefSeq (protein)	NP_001257997.1 NP_002373.3 NP_660087.1 NP_660088.1 NP_660089.1 NP_932061.1 NP_002373.3 NP_660087.1 NP_660088.1 NP_001307344.1	n/a
Location (UCSC)	Chr 14: 65.01 – 65.1 Mb	Chr 12: 76.94 – 76.96 Mb
PubMed search	[1]	[2]
Wikidata

Protein max also known as myc-associated factor X is a protein that in humans is encoded by the MAX gene.^[3][4]

Function

The protein max is a member of the basic helix-loop-helix leucine zipper (bHLHZ) family of transcription factors. It is able to form homodimers and heterodimers with other family members, which include Mad, Mxl1 and Myc. Myc is an oncoprotein implicated in cell proliferation, differentiation and apoptosis. The homodimers and heterodimers compete for a common DNA target site (the E-box) and rearrangement among these dimer forms provides a complex system of transcriptional regulation. Multiple alternatively spliced transcript variants have been described for this gene but the full-length nature for some of them is unknown.^[4]

Max binds to itself and to other transcription factors through its leucine zipper to form homo- and hetero-dimers respectively. Max itself lacks a transactivation domain so that Max homodimers have a repressive function. In contrast, Myc contains a transactivation domain but cannot homodimerize. However Myc can heterodimerize with Max to form heterodimers that can both bind DNA and transactivate. The transcriptionally active Max/Myc dimer promotes cell proliferation as well as apoptosis.^[5]

Interactions

MAX (gene) has been shown to interact with:

• Myc,^{[6][7][8][9][10][11][12][13][14][15][16][17][18]}
• MNT,^[15]
• MSH2,^[10]
• MXD1,^{[12][14][16][19]}
• MXI1,^{[13][15][17][20]}
• MYCL1,^[11][17]
• N-Myc,^[11][17]
• SPAG9,^[12]
• TEAD1,^[21] and
• Transformation/transcription domain-associated protein.^[7][8]

Clinical relevance

This gene has been shown mutated in cases of hereditary pheochromocytoma.^[22] More recently the MAX gene has been shown to be mutated also in small cell lung cancer (SCLC). This is mutually exclusive with alterations at MYC and BRG1, the latter coding for an ATPase of the SWI/SNF complex. It was demonstrated that BRG1 regulates the expression of MAX through direct recruitment to the MAX promoter, and that depletion of BRG1 strongly hinders cell growth, specifically in MAX-deficient cells, heralding a synthetic lethal interaction. Furthermore, MAX required BRG1 to activate neuroendocrine transcriptional programs and to up-regulate MYC-targets, such as glycolytic-related genes.^[23]

References

Further reading

External links

• MAX protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
• FactorBook Max

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

PDB gallery
1an2: RECOGNITION BY MAX OF ITS COGNATE DNA THROUGH A DIMERIC B/HLH/Z DOMAIN  1hlo: THE CRYSTAL STRUCTURE OF AN INTACT HUMAN MAX-DNA COMPLEX: NEW INSIGHTS INTO MECHANISMS OF TRANSCRIPTIONAL CONTROL  1nkp: Crystal structure of Myc-Max recognizing DNA  1nlw: Crystal structure of Mad-Max recognizing DNA  1r05: Solution Structure of Max B-HLH-LZ