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Description:
Trace amines are endogenous molecules structurally related to classical biogenic amines that are linked to psychiatric conditions. A family of G-protein coupled receptors referred to as trace-amine-associated receptors (TAAR) are activated by trace amines and are present in very low levels in mammalian tissue. TaRs contain several structural features that are similar to the rhodopsin ∫-adrenergic receptor superfamily, including the positions of the seven transmembrane regions that provide common ligand-binding pockets as well as the short N- and C-terminal domains. TAAR proteins are potential targets for drugs of abuse, such as amphetamine and MDMA, as well as neuropsychiatric disorders including schizophrenia, depression, and attention deficit disorder.
Description:
With 181 million base pairs encoding around 1,000 genes, chromosome 5 is about 6% of human genomic DNA. It is associated with Cockayne syndrome through the ERCC8 gene and familial adenomatous polyposis through the adenomatous polyposis coli (APC) tumor suppressor gene. Treacher Collins syndrome is also chromosome 5 associated and is caused by insertions or deletions within the TCOF1 gene. Deletion of the p arm of chromosome 5 leads to Cri du chat syndrome. Deletion of 5q or chromosome 5 altogether is common in therapy-related acute myelogenous leukemias and myelodysplastic syndrome.
Description:
Glutamate receptors mediate most excitatory neurotransmission in the brain and play an important role in neural plasticity, neural development and neurodegeneration. Ionotropic glutamate receptors are categorized into NMDA receptors and kainate/AMPA receptors, both of which contain glutamate-gated, cation-specific ion channels. Kainate/AMPA receptors are co-localized with NMDA receptors in many synapses and consist of the structurally related subunits GluR-1 to -7, KA1 and KA2. KA1 (also designated EEA1) and KA2 (also designated EEA2) form heteromeric receptors with GluR subunits when coexpressed, forming ion channels with various properties. The kainate/AMPA receptors are primarily responsible for the fast excitatory neuro-transmission by glutamate.
Description:
This gene encodes a transmembrane signaling polypeptide which contains an immunoreceptor tyrosine-based activation motif (ITAM) in its cytoplasmic domain. The encoded protein may associate with the killer-cell inhibitory receptor (KIR) family of membrane glycoproteins and may act as an activating signal transduction element. This protein may bind zeta-chain (TCR) associated protein kinase 70kDa (ZAP-70) and spleen tyrosine kinase (SYK) and play a role in signal transduction, bone modeling, brain myelination, and inflammation. Mutations within this gene have been associated with polycystic lipomembranous osteodysplasia with sclerosing leukoencephalopathy (PLOSL), also known as Nasu-Hakola disease. Its putative receptor, triggering receptor expressed on myeloid cells 2 (TREM2), also causes PLOSL. Multiple alternative transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Mar 2010]
Description:
GLT25D1 is a 622 amino acid protein that localizes to the lumen of the endoplasmic reticulum. Ubiquitously expressed with higher levels in placenta, heart, lung and spleen, GLT25D1 is a member of the glycosyltransferase 25 family. The beta-galactosyltransferase activity of GLT25D1 allows the transfer of beta-galactose to hydroxylysine residues of collagen. GLT25D1 is considered an important target for investigating the biological significance of collagen glycosylation and the importance of posttranslational modification in the etiology of connective tissue disorders. The gene encoding GLT25D1 is located on human chromosome 19, which consists of over 63 million bases, houses approximately 1,400 genes and is recognized for having the greatest gene density of the human chromosomes.
Description:
Steroid receptors are ligand-dependent, intracellular proteins that stimulate transcription of specific genes by binding to specific DNA sequences following activation by the appropriate hormone. Glucocorticoids are a family of steroids necessary for the regulation of energy metabolism and the immune and inflammatory responses. These compounds exert their effect through their interaction with the glucocoticoid receptor (GR) and that complex's subsequent association with DNA. All normal mammalian tissues examined to date have been shown to contain glucocorticoid receptor.
Description:
In eukaryotes, it is essential to have the ability to detect and degrade transcripts that lack full coding potential. Nonsense-mediated RNA decay (NMD) protects the organism by avoiding the translation of truncated peptides with dominant negative or deleterious gain-of-function potential. Rent1, a mammalian ortholog of Upflp, is essential for embryonic viability (1–3). Rent1 (also designated regulator of nonsense transcripts and HUpf1) contains an N-terminal zinc finger-like domain, NTPase domains and a region comprised of domains that define Rent1 as a superfamily group I helicase.
Description:
Glutathione (GSH) is a tripeptide antioxidant that reduces disulfide bonds between cytoplasmic proteins. The constitutive enzyme glutathione reductase transforms glutathione into its reduced state, which ultimately can provide a measure of cellular toxicity. GSTCD (glutathione S-transferase, C-terminal domain containing) is a 633 amino acid protein belonging to the GSTCD family and contains one GST C-terminal domain. The gene encoding GSTCD maps to human chromosome 4, which represents approximately 6% of the human genome and contains nearly 900 genes. Notably, the Huntingtin gene, which is found to encode an expanded glutamine tract in cases of Huntington's disease, is on chromosome 4. FGFR-3 is also encoded on chromosome 4 and has been associated with thanatophoric dwarfism, achondroplasia, Muenke syndrome and bladder cancer. Chromosome 4 is also tied to Ellis-van Creveld syndrome, methylmalonic acidemia and polycystic kidney disease.
Description:
The GINS complex is composed of four subunits, encoded by SLD5, PSF1, PSF2, and PSF3. In S. cerevisiae, it was first identified by genetic and biochemical methods to determine factors interacting with Sld5p. Genetic interactions between these four genes also suggest that they act together. The GINS complex was independently isolated in a large scale screen for cell cycle defects. A similar complex is found in Xenopus and has a ring-like structure. In yeast, all four genes are essential and cells defective in SLD5, PSF1, or PSF2 are impaired in their ability to replicate DNA. The complex localizes to origins of DNA replication and Sld5p was previously implicated as functioning in DNA replication due to its genetic interaction with DPB11. Additional genetic and biochemical interactions of the GINS complex with Dpb11p, Dpb2p, and Sld3p suggest that it functions in some way at the replication fork during DNA synthesis.
Description:
GRAMD2 is a 354 amino acid single-pass membrane protein that contains one GRAM domain and is encoded by a gene that maps to human chromosome 15q23. Encoding more than 700 genes, chromosome 15 is made up of approximately 106 million base pairs and is about 3% of the human genome. Angelman and Prader-Willi syndromes are associated with loss of function or deletion of genes in the 15q11-q13 region. In the case of Angelman syndrome, this loss is due to inactivity of the maternal 15q11-q13 encoded UBE3A gene in the brain by either chromosomal deletion or mutation. In cases of Prader-Willi syndrome, there is a partial or complete deletion of this region from the paternal copy of chromosome 15. Tay-Sachs disease is a lethal disorder associated with mutations of the HEXA gene, which is encoded by chromosome 15. Marfan syndrome is associated with chromosome 15 through the FBN1 gene.
Description:
Myotubularin-related protein 14 (MTMR14), also known as Jumpy, is a myotubularin-related phosphoinositol-3-phosphate (PI3P) phosphatase (1). Mutations in the MTMR14 gene have been associated with centronuclear myopathy (1). MTMR14 deficiency in mice leads to altered calcium homeostasis and muscle disorders (2). MTMR14 has also been shown to play a role in autophagy, a process that is highly regulated by phosphatidylinositides through the type III PI3K, Vps34 (3). MTMR14 was localized to autophagic isolation membranes and early autophagosomes (3). In these studies, MTMR14 inhibited autophagy and mutations of MTMR14 associated with centronuclear myopathy were also defective in autophagy inhibition. In zebrafish, MTMR14 knockdown was shown to increase the number of autophagosomes, suggesting that its activity is associated with an inhibition of autophagy (4).
Description:
ATP-binding cassette (ABC) transporters are an evolutionarily conserved family of widely-expressed proteins that use ATP hydrolysis to catalyze the transport of various molecules across extracellular and intracellular membranes. Eukaryotic ABC transporters are largely responsible for trafficking hydrophobic compounds either within the cell as part of a metabolic process, outside the cell for transport to other organs, or for secretion from the body. The cholesterol-responsive transporter, ABCA7, maps to human chromosome 19 and mouse chromosome 10 and has been reported as a candidate regulator of ceramide transport in epidermal lipid reorganization. High expression levels of ABCA7 have been reported in myelolymphatic tissues, reticuloendothelial cells, peripheral leukocytes, thymus, spleen and bone marrow. This expression pattern of the two alternatively-spliced isoforms also indicates an involvement in lipid homeostasis in cells of the immune system, though the complete role of ABCA7 is not yet known. Full-length type I ABCA7 has shown plasma membrane localization, while the type II splicing variant has shown expression predominantly in the endoplasmic reticulum.
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