In molecular biology there are a number of

neurogenic In biology, the nervous system is the highly complex part of an animal that coordinates its actions and sensory information by transmitting signals to and from different parts of its body. The nervous system detects environmental changes ...

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...

s referred to as mastermind-like proteins (MAMLs) of which this domain is the N-terminal region. Mastermind-like proteins act as critical transcriptional co-activators for Notch signaling. The N-terminal domain of MAML proteins,

MAML1 Mastermind-like protein 1 is a protein that in humans is encoded by the ''MAML1'' gene. Function This protein is the human homolog of mastermind, a Drosophila protein that plays a role in the Notch signaling pathway involved in cell-fate deter ...

MAML2 Mastermind-like protein 2 is a protein that in humans is encoded by the ''MAML2'' gene. See also Details on the activity of the N-terminal domain Domain may refer to: Mathematics *Domain of a function, the set of input values for which the (t ...

, MAML3, is a polypeptide of up to 70 residues, numbers 15-67 of which adopt an elongated kinked

helix A helix () is a shape like a corkscrew or spiral staircase. It is a type of smooth space curve with tangent lines at a constant angle to a fixed axis. Helices are important in biology, as the DNA molecule is formed as two intertwined helic ...

that wraps around ANK and CSL forming one of the complexes in the build-up of the Notch transcriptional

complex Complex commonly refers to: * Complexity, the behaviour of a system whose components interact in multiple ways so possible interactions are difficult to describe ** Complex system, a system composed of many components which may interact with each ...

for recruiting general

transcription factor In molecular biology, a transcription factor (TF) (or sequence-specific DNA-binding factor) is a protein that controls the rate of transcription of genetic information from DNA to messenger RNA, by binding to a specific DNA sequence. The f ...

s. This N-terminal domain is responsible for its interaction with the

ankyrin repeat The ankyrin repeat is a 33-residue motif in proteins consisting of two alpha helices separated by loops, first discovered in signaling proteins in yeast Cdc10 and ''Drosophila'' Notch. Domains consisting of ankyrin tandem repeats mediate prot ...

region of the Notch proteins NOTCH1, NOTCH2, NOTCH3 and NOTCH4. It forms a DNA-binding complex with Notch proteins and RBPSUH/RBP-J kappa/CBF1, and also

bind BIND () is a suite of software for interacting with the Domain Name System (DNS). Its most prominent component, named (pronounced ''name-dee'': , short for ''name daemon''), performs both of the main DNS server roles, acting as an authoritative ...

s CREBBP/CBP and CDK8. The C-terminal region is required for transcriptional activation. Notch

receptor Receptor may refer to: * Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a ...

s are cleaved upon

ligand In coordination chemistry, a ligand is an ion or molecule ( functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's elec ...

engagement and the

intracellular This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...

domain of Notch shuttles to the

nucleus Nucleus ( : nuclei) is a Latin word for the seed inside a fruit. It most often refers to: *Atomic nucleus, the very dense central region of an atom * Cell nucleus, a central organelle of a eukaryotic cell, containing most of the cell's DNA Nucl ...

. MAMLs form a functional DNA-binding

with the cleaved Notch

and the

CSL, thereby regulating transcriptional events that are specific to the Notch pathway. MAML

s may also play roles as key transcriptional co-activators in other signal transduction pathways as well, including: muscle differentiation and myopathies (MEF2C), tumour suppressor pathway (p53) and colon carcinoma

survival Survival, or the act of surviving, is the propensity of something to continue existing, particularly when this is done despite conditions that might kill or destroy it. The concept can be applied to humans and other living things (or, hypotheti ...

(beta-catenin). MAML proteins could mediate cross-talk among the various

signaling pathways Signal transduction is the process by which a chemical or physical signal is transmitted through a cell as a series of molecular events, most commonly protein phosphorylation catalyzed by protein kinases, which ultimately results in a cellula ...

and the diverse activities of the MAML proteins converge to impact normal biological processes and

human Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, cultu ...

diseases, including

cancer Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal b ...

References

{{InterPro content, IPR019082 Protein domains