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Basic Helix–loop–helix
A basic helix–loop–helix (bHLH) is a protein structural motif that characterizes one of the largest families of dimerizing transcription factors. The word "basic" does not refer to complexity but to the chemistry of the motif because transcription factors in general contain basic amino acid residues in order to facilitate DNA binding. bHLH transcription factors are often important in development or cell activity. For one, BMAL1-Clock (also called ARNTL) is a core transcription complex in the molecular circadian clock. Other genes, like c-Myc and HIF-1, have been linked to cancer due to their effects on cell growth and metabolism. Structure The motif is characterized by two α-helices connected by a loop. In general, transcription factors (including this type) are dimeric, each with one helix containing basic amino acid residues that facilitate DNA binding. In general, one helix is smaller, and due to the flexibility of this loop, allows dimerization by folding and ...
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Helix-turn-helix
Helix-turn-helix is a DNA-binding protein (DBP). The helix-turn-helix (HTH) is a major structural motif capable of binding DNA. Each monomer incorporates two α helices, joined by a short strand of amino acids, that bind to the major groove of DNA. The HTH motif occurs in many proteins that regulate gene expression. It should not be confused with the helix–loop–helix motif. Discovery The discovery of the helix-turn-helix motif was based on similarities between several genes encoding transcription regulatory proteins from bacteriophage lambda and ''Escherichia coli'': Cro, CAP, and λ repressor, which were found to share a common 20–25 amino acid sequence that facilitates DNA recognition. Function The helix-turn-helix motif is a DNA-binding motif. The recognition and binding to DNA by helix-turn-helix proteins is done by the two α helices, one occupying the N-terminal end of the motif, the other at the C-terminus. In most cases, such as in the Cro repressor, the second ...
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Palindromic Sequence
A palindromic sequence is a nucleic acid sequence in a double-stranded DNA or RNA molecule whereby reading in a certain direction (e.g. 5' to 3') on one strand is identical to the sequence in the same direction (e.g. 5' to 3') on the complementary strand. This definition of palindrome thus depends on complementary strands being palindromic of each other. The meaning of palindrome in the context of genetics is slightly different from the definition used for words and sentences. Since a double helix is formed by two paired antiparallel strands of nucleotides that run in opposite directions, and the nucleotides always pair in the same way (adenine (A) with thymine (T) in DNA or uracil (U) in RNA; cytosine (C) with guanine (G)), a (single-stranded) nucleotide sequence is said to be a palindrome if it is equal to its reverse complement. For example, the DNA sequence ACCTAGGT is palindromic with its nucleotide-by-nucleotide complement TGGATCCA because reversing the order of the nuc ...
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TCF4
Transcription factor 4 (TCF-4) also known as immunoglobulin transcription factor 2 (ITF-2) is a protein that in humans is encoded by the TCF4 gene located on chromosome 18q21.2. Function TCF4 proteins act as transcription factors which will bind to the immunoglobulin enhancer mu-E5/kappa-E2 motif. TCF4 activates transcription by binding to the E-box (5’-CANNTG-3’) found usually on SSTR2-INR, or somatostatin receptor 2 initiator element. TCF4 is primarily involved in neurological development of the fetus during pregnancy by initiating neural differentiation by binding to DNA. It is found in the central nervous system, somites, and gonadal ridge during early development. Later in development it will be found in the thyroid, thymus, and kidneys while in adulthood TCF4 it is found in lymphocytes, muscles, mature neurons, and gastrointestinal system. Clinical significance Mutations in TCF4 cause Pitt-Hopkins Syndrome (PTHS). These mutations cause TCF4 proteins to not bin ...
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N-Myc
N-myc proto-oncogene protein also known as N-Myc or basic helix-loop-helix protein 37 (bHLHe37), is a protein that in humans is encoded by the ''MYCN'' gene. Function The ''MYCN'' gene is a member of the MYC family of transcription factors and encodes a protein with a basic helix-loop-helix ( bHLH) domain. This protein is located in the cell nucleus and must dimerize with another bHLH protein in order to bind DNA. N-Myc is highly expressed in the fetal brain and is critical for normal brain development. The ''MYCN'' gene has an antisense RNA, N-cym or ''MYCNOS'', transcribed from the opposite strand which can be translated to form a protein product. N-Myc and ''MYCNOS'' are co-regulated both in normal development and in tumor cells, so it is possible that the two transcripts are functionally related. It has been shown that the antisense RNA encodes for a protein, named NCYM, that has originated ''de novo'' and is specific to human and chimpanzee. This NCYM protein inhibits GSK ...
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C-myc
''Myc'' is a family of regulator genes and proto-oncogenes that code for transcription factors. The ''Myc'' family consists of three related human genes: ''c-myc'' (MYC), ''l-myc'' (MYCL), and ''n-myc'' (MYCN). ''c-myc'' (also sometimes referred to as ''MYC'') was the first gene to be discovered in this family, due to homology with the viral gene ''v-myc''. In cancer, ''c-myc'' is often constitutively (persistently) expressed. This leads to the increased expression of many genes, some of which are involved in cell proliferation, contributing to the formation of cancer. A common human translocation involving ''c-myc'' is critical to the development of most cases of Burkitt lymphoma. Constitutive upregulation of ''Myc'' genes have also been observed in carcinoma of the cervix, colon, breast, lung and stomach. Myc is thus viewed as a promising target for anti-cancer drugs. Unfortunately, Myc possesses several features that render it undruggable such that any anti-cancer drugs f ...
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MAX (gene)
''MAX'' (also known as myc-associated factor X) is a gene that in humans encodes the MAX transcription factor. Function The protein product of ''MAX'' contains the basic helix-loop-helix and leucine zipper motifs. It is therefore included in the bHLHZ family of transcription factors. It is able to form homodimers with other MAX proteins and heterodimers with other transcription factors, including Mad, Mxl1 and Myc. The homodimers and heterodimers compete for a common DNA target site (the E-box) in a gene promoter zone. Rearrangement of dimers (e.g., Mad:Max, Max:Myc) provides a system of transcriptional regulation with greater diversity of gene targets. Max must dimerise in order to be biologically active. Transcriptionally active hetero- and homodimers involving Max can promote cell proliferation as well as apoptosis. Interactions The protein product of Max has been shown to interact with: * Myc, * MNT, * MSH2, * MXD1, * MXI1, * MYCL1, * N-Myc, * SPAG9, * TEAD1, and ...
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Neurogenins
Neurogenins are a family of bHLH transcription factors involved in specifying neuronal differentiation. It is one of many gene families related to the ''atonal'' gene in Drosophila. Other positive regulators of neuronal differentiation also expressed during early neural development include NeuroD and ASCL1. In neural crest cells, the neurogenin family is essential for neurogenesis in the developing dorsal root ganglia and development of the sensory lineage. Neurogenin-1 Neurogenin 1 (Ngn1) is a Class-A basic-helix-loop-helix (bHLH) transcription factor that acts as a regulator for neuronal differentiation, and acts by binding to enhancer regulatory elements on genes that encode transcriptional regulators of neurogenesis. In order for Ngn1 to bind with high fidelity with genomic DNA, it must dimerize with another bHLH protein. Ngn1 is a proneural gene because its expression is seen prior to neural lineage determination, indicating it plays a role in neuronal differentia ...
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NeuroD
NeuroD, also called Beta2, is a basic helix-loop-helix transcription factor expressed in certain parts of brain, beta pancreatic cells and enteroendocrine cells. It is involved in the differentiation of nervous system and development of pancreas. It heterodimerizes with the products of E2A gene and controls the transcription of a variety of genes by identifying and binding E boxes in their promoter region. In rodents NeuroD is involved in the development of the retina. In mammals there are two types of this factor: *NeuroD1 Neurogenic differentiation 1 (Neurod1), also called β2, is a transcription factor of the NeuroD-type. It is encoded by the human gene NEUROD1. In mice, ''Neurod1'' expression is first seen at embryonic day 12 (E12). It is a member of the Neurod ... * NeuroD2 * NeuroD4 * NeuroD6 References Transcription factors {{biochemistry-stub ...
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P-CaMKII
CAMK, also written as CaMK or CCaMK, is an abbreviation for the Ca2+/calmodulin-dependent protein kinase class of enzymes. CAMKs are activated by increases in the concentration of intracellular calcium ions (Ca2+) and calmodulin. When activated, the enzymes transfer phosphates from ATP to defined serine or threonine residues in other proteins, so they are serine/threonine-specific protein kinases. Activated CAMK is involved in the phosphorylation of transcription factors and therefore, in the regulation of expression of responding genes. CAMK also works to regulate the cell life cycle (i.e. programmed cell death), rearrangement of the cell's cytoskeletal network, and mechanisms involved in the learning and memory of an organism. Types There are 2 common types of CAM Kinase proteins: specialized and multi-functional CAM kinases. ;Substrate-specific CAM Kinases: only have one target that they can phosphorylate, such as myosin light chain kinases. This group of proteins includes C ...
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Tal1
__NOTOC__ T-cell acute lymphocytic leukemia protein 1 (i.e. TAL1 but also termed stem cell leukemia/T-cell acute leukemia 1 .e. SCL/TAL1 is a protein that in humans is encoded by the ''TAL1'' gene. The protein encoded by TAL1 is a basic helix-loop-helix transcription factor. Interactions TAL1 has been shown to interact with: * CBFA2T3, * EP300, * GATA1, * LDB1, * LMO1, * LMO2, * SIN3A, * Sp1 transcription factor, and * TCF3 Transcription factor 3 (E2A immunoglobulin enhancer-binding factors E12/E47), also known as TCF3, is a protein that in humans is encoded by the ''TCF3'' gene. TCF3 has been shown to directly enhance Hes1 (a well-known target of Notch signaling) ex .... References Further reading * * * * * * * * * * * * * * * * * * External links * * Transcription factors {{gene-1-stub ...
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TAL1
__NOTOC__ T-cell acute lymphocytic leukemia protein 1 (i.e. TAL1 but also termed stem cell leukemia/T-cell acute leukemia 1 .e. SCL/TAL1 is a protein that in humans is encoded by the ''TAL1'' gene. The protein encoded by TAL1 is a basic helix-loop-helix transcription factor. Interactions TAL1 has been shown to interact with: * CBFA2T3, * EP300, * GATA1, * LDB1, * LMO1, * LMO2, * SIN3A, * Sp1 transcription factor, and * TCF3 Transcription factor 3 (E2A immunoglobulin enhancer-binding factors E12/E47), also known as TCF3, is a protein that in humans is encoded by the ''TCF3'' gene. TCF3 has been shown to directly enhance Hes1 (a well-known target of Notch signaling) ex .... References Further reading * * * * * * * * * * * * * * * * * * External links * * Transcription factors {{gene-1-stub ...
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NEUROD1
Neurogenic differentiation 1 (Neurod1), also called β2, is a transcription factor of the NeuroD-type. It is encoded by the human gene NEUROD1. In mice, ''Neurod1'' expression is first seen at embryonic day 12 (E12). It is a member of the Neurod family of basic helix-loop-helix (bHLH) transcription factors, composed of Neurod1, Neurod2, Neurod4, and Neurod6. The protein forms heterodimers with other bHLH proteins and activates transcription of genes that contain a specific DNA sequence known as the E-box. It regulates expression of the insulin gene, and mutations in this gene result in type II diabetes mellitus in mouse models and in human clinical patients. ''Neurod1'' is found to convert reactive glial cells into functional neurons in the mouse brain ''in vivo'' In the adult cortex, ''Neurod1'' expression is a marker of mature excitatory pyramidal neurons in the upper-most layers of the cortex. Interactions Neurod1 has been shown to interact with MAP3K10 Mitogen-activated ...
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