Single-minded homolog 1, also known as class E basic helix-loop-helix protein 14 (bHLHe14), is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

that in humans is encoded by the ''SIM1''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

Function

The ''SIM1'' and ''

SIM2 Single-minded homolog 2 is a protein that in humans is encoded by the ''SIM2'' gene. It plays a major role in the development of the central nervous system midline as well as the construction of the face and head. Function '' SIM1'' and ''SIM ...

'' genes are homologs of ''

Drosophila melanogaster ''Drosophila melanogaster'' is a species of fly (an insect of the Order (biology), order Diptera) in the family Drosophilidae. The species is often referred to as the fruit fly or lesser fruit fly, or less commonly the "vinegar fly", "pomace fly" ...

'' single-minded (''sim''), so named because cells in the midline of the sim mutant embryo fail to properly develop and eventually die, and thus the paired longitudinal axon bundles that span the anterior-posterior axis of the embryo (analogous to the embryo's spinal cord) are collapsed into a "single" rudimentary axon bundle at the midline. SIM is a

basic helix-loop-helix Basic or BASIC may refer to: Science and technology * BASIC, a computer programming language * Basic (chemistry), having the properties of a base * Basic access authentication, in HTTP Entertainment * ''Basic'' (film), a 2003 film * Basic, one ...

–

PAS domain A Per-Arnt-Sim (PAS) domain is a protein domain found in all kingdoms of life. Generally, the PAS domain acts as a molecular sensor, whereby small molecules and other proteins associate via binding of the PAS domain. Due to this sensing capabilit ...

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

that regulates gene expression in the midline cells. Because the ''sim'' gene plays an important role in ''Drosophila'' development and has peak levels of expression during the period of

neurogenesis Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells (NSCs). This occurs in all species of animals except the porifera (sponges) and placozoans. Types of NSCs include neuroepithelial cells ( ...

, it was proposed that the human ''SIM2'' gene, which resides in a critical region of chromosome 21, is a candidate for involvement in certain dysmorphic features (particularly facial and skull characteristics), abnormalities of brain development, or mental retardation of Down syndrome.

Clinical significance

Haploinsufficiency Haploinsufficiency in genetics describes a model of dominant gene action in diploid organisms, in which a single copy of the wild-type allele at a locus in heterozygous combination with a variant allele is insufficient to produce the wild-type ...

of ''SIM1'' has been shown to cause severe early-onset obesity in a human girl with a ''de novo'' balanced translocation between chromosomes 1p22.1 and 6q16.2 and has been suggested to cause a Prader-Willi-like phenotype in other cases. Additionally, studies in mice have shown that haploinsufficiency of Sim1 causes obesity that is due to hyperphagia and do not respond properly to increased dietary fat. Overexpression of ''SIM1'' protects against diet induced obesity and rescues the hyperphagia of agouti yellow mice, who have disrupted

melanocortin The melanocortins are a family of neuropeptide hormones which are the ligands of the melanocortin receptors.Ericson, M.D., et al., ''Bench-top to clinical therapies: A review of melanocortin ligands from 1954 to 2016.'' Biochim Biophys Acta Mol B ...

signaling. The obesity and hyperphagia may be mediated by impaired melanocortin activation of PVN neurons and

oxytocin Oxytocin is a peptide hormone and neuropeptide normally produced in the hypothalamus and released by the posterior pituitary. Present in animals since early stages of evolution, in humans it plays roles in behavior that include Human bonding, ...

deficiency in these mice. It has been demonstrated that modulating SIM1 levels postnatally also leads to hyperphagia and obesity, suggesting a physiological role for SIM1 separate from its role in development.

Interactions

SIM1 has been shown to interact with

aryl hydrocarbon receptor nuclear translocator The ''ARNT'' gene encodes the aryl hydrocarbon receptor nuclear translocator protein that forms a complex with ligand-bound aryl hydrocarbon receptor (AhR), and is required for receptor function. The encoded protein has also been identified as th ...

Function

Clinical significance

Interactions

References

Further reading