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PSEN2
Presenilin-2 is a protein that (in humans) is encoded by the ''PSEN2'' gene. Function Alzheimer's disease (AD) patients with an inherited form of the disease carry mutations in the presenilin proteins ( PSEN1; PSEN2) or the amyloid precursor protein (APP). These disease-linked mutations result in increased production of the longer form of amyloid-beta (main component of amyloid deposits found in AD brains). Presenilins are postulated to regulate APP processing through their effects on gamma-secretase, an enzyme that cleaves APP. Also, it is thought that the presenilins are involved in the cleavage of the Notch receptor, such that they either directly regulate gamma-secretase activity or themselves are protease enzymes. Two alternative transcripts of PSEN2 have been identified. In melanocytic cells PSEN2 gene expression may be regulated by MITF. Interactions PSEN2 has been shown to interact with: * BCL2-like 1, * CAPN1, * CIB1, * Calsenilin, * FHL2, * FLNB, * KCN ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Presenilin
Presenilins are a family of related multi-pass transmembrane proteins which constitute the catalytic subunits of the gamma-secretase intramembrane protease protein complex. They were first identified in screens for mutations causing early onset forms of familial Alzheimer's disease by Peter St George-Hyslop. Vertebrates have two presenilin genes, called '' PSEN1'' (located on chromosome 14 in humans) that codes for presenilin 1 (PS-1) and '' PSEN2'' (on chromosome 1 in humans) that codes for presenilin 2 (PS-2). Both genes show conservation between species, with little difference between rat and human presenilins. The nematode worm ''C. elegans'' has two genes that resemble the presenilins and appear to be functionally similar, sel-12 and hop-1. Presenilins undergo cleavage in an alpha helical region of one of the cytoplasmic loops to produce a large N-terminal and a smaller C-terminal fragment that together form part of the functional protein. Cleavage of presenilin 1 can be ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
BCL2-like 1 (gene)
Bcl-2-like protein 1 is a protein encoded in humans by the ''BCL2L1'' gene. Through alternative splicing, the gene encodes both of the human proteins Bcl-xL and Bcl-xS. Function The protein encoded by this gene belongs to the Bcl-2 protein family. Bcl-2 family members form hetero- or homodimers and act as anti- or pro-apoptotic regulators that are involved in a wide variety of cellular activities. The proteins encoded by this gene are located at the outer mitochondrial membrane, and have been shown to regulate outer mitochondrial membrane channel (voltage-dependent anion channels (VDACs) opening. VDACs regulate mitochondrial membrane potential, and thus controls the production of reactive oxygen species and release of cytochrome C by mitochondria, both of which are the potent inducers of cell apoptosis. Two alternatively spliced transcript variants, which encode distinct isoforms, have been reported. The longer isoform (Bcl-xL) acts as an apoptotic inhibitor and the shorter ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Alzheimer's Disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term memory, remembering recent events. As the disease advances, symptoms can include primary progressive aphasia, problems with language, Orientation (mental), disorientation (including easily getting lost), mood swings, loss of motivation, self-neglect, and challenging behaviour, behavioral issues. As a person's condition declines, they often withdraw from family and society. Gradually, bodily functions are lost, ultimately leading to death. Although the speed of progression can vary, the typical life expectancy following diagnosis is three to nine years. The cause of Alzheimer's disease is poorly understood. There are many environmental and genetic risk factors associated with its development. The strongest genetic risk factor is from an alle ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
PSEN1
Presenilin-1 (PS-1) is a presenilin protein that in humans is encoded by the ''PSEN1'' gene. Presenilin-1 is one of the four core proteins in the gamma secretase complex, which is considered to play an important role in generation of amyloid beta (Aβ) from amyloid-beta precursor protein (APP). Accumulation of amyloid beta is associated with the onset of Alzheimer's disease. Structure Presenilin possesses a 9 transmembrane domain topology, with an extracellular C-terminus and a cytosolic N-terminus. Presenilin undergoes endo-proteolytic processing to produce ~27-28 kDa N-terminal and ~16-17 kDa C-terminal fragments in humans. Furthermore, presenilin exists in the cell mainly as a heterodimer of the C-terminal and N-terminus fragments. When presenilin 1 is overexpressed, the full length protein accumulates in an inactive form. Based on evidence that a gamma-secretase inhibitor binds to the fragments, the cleaved presenilin complex is considered to be the active form. Function ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
UBQLN1
Ubiquilin-1 is a protein that in humans is encoded by the ''UBQLN1'' gene. Ubiquilins contain two domains, an N-terminal ubiquitin-like domain and a C-terminal ubiquitin-associated domain. They physically associate with both proteasomes and ubiquitin ligases, and thus are thought to functionally link the ubiquitination machinery to the proteasome to effect ''in vivo'' protein degradation. Functions Ubiquilin-1 is associated with protein degradation and aggregation of misfolded proteins, and may be involved in neurodegenerative diseases. Ubiquilin-1 has been reported to act as a molecular chaperone for amyloid precursor protein (APP), a protein associated with Alzheimer's disease. * Ubiquilin-1 was first identified through its interactions with presenilins. Two transcript variants encoding different isoforms have been found for this gene. Related proteins Human UBQLN1 shares a high degree of similarity with related ubiquilins including UBQLN2 and UBQLN4. Interactions UBQL ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Nicastrin
Nicastrin, also known as NCSTN, is a protein that in humans is encoded by the ''NCSTN'' gene. Function Nicastrin (abbreviated NCT) is a protein that is part of the gamma secretase protein complex, which is one of the proteases involved in processing amyloid precursor protein (APP) to the short Alzheimer's disease-associated peptide amyloid beta. The other proteins in the complex are PSEN1 (presenilin-1), which is the catalytically active component of the complex, APH-1 (anterior pharynx-defective 1), and PEN-2 (presenilin enhancer 2). Nicastrin itself is not catalytically active, but instead promotes the maturation and proper trafficking of the other proteins in the complex, all of which undergo significant post-translational modification before becoming active in the cell. Nicastrin has also been identified as a regulator of neprilysin, an enzyme involved in the degradation of amyloid beta fragment. History The protein was named after the Italian country Nicastro, reflecting th ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
KCNIP4
Kv channel-interacting protein 4 is a protein that in humans is encoded by the ''KCNIP4'' gene. This gene encodes a member of the family of voltage-gated potassium (Kv) channel-interacting proteins (KCNIPs), which belong to the recoverin branch of the EF-hand superfamily. Members of the KCNIP family are small calcium binding proteins. They all have EF-hand-like domains, and differ from each other in the N-terminus. They are integral subunit components of native Kv4 channel complexes. They may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium. This protein member also interacts with presenilin. Multiple alternatively spliced transcript variants encoding distinct isoforms have been identified for this gene. Interactions KCNIP4 has been shown to interact with PSEN2. See also * Voltage-gated potassium channel Voltage-gated potassium channels (VGKCs) are transmembrane channels specific for potassium and sensitive to volt ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FLNB
Filamin B, beta (FLNB), also known as Filamin B, beta (truncated actin binding protein 278 homolog), is a cytoplasmic protein which in humans is encoded by the ''FLNB'' gene. FLNB regulates intracellular communication and signalling by cross-linking the protein actin to allow direct communication between the cell membrane and cytoskeletal network, to control and guide proper skeletal development. Mutations in the FLNB gene are involved in several lethal bone dysplasias, including boomerang dysplasia and atelosteogenesis type I. Interactions FLNB has been shown to interact with GP1BA, Filamin, FBLIM1, PSEN1, CD29 and PSEN2. See also * Larsen syndrome Larsen syndrome (LS) is a congenital disorder discovered in 1950 by Larsen and associates when they observed dislocation of the large joints and face anomalies in six of their patients.Mitra, N., Kannan, N., Kumar, V.S., Kavita, G. "Larsen Syndrome ... References External links GeneReview/NIH/UW entry on FLNB-Related Disorders ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
FHL2
Four and a half LIM domains protein 2 also known as FHL-2 is a protein that in humans is encoded by the ''FHL2'' gene. LIM proteins contain a highly conserved double zinc finger motif called the LIM domain. Function FHL-2 is thought to have a role in the assembly of extracellular membranes and may function as a link between presenilin-2 and an intracellular signaling pathway. Family The Four-and-a-half LIM (FHL)-only protein subfamily is one of the members of the LIM-only protein family. Protein members within the group might be originated from a common ancestor and share a high degree of similarity in their amino acid sequence. These proteins are defined by the presence of the four and a half cysteine-rich LIM homeodomain with the half-domain always located in the N-terminal. The name LIM was derived from the first letter of the transcription factors LIN-11, ISL-1 and MEC-3, from which the domain was originally characterized. No direct interactions between LIM domain and ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
Calsenilin
Calsenilin is a protein that in humans is encoded by the ''KCNIP3'' gene. Function This gene encodes a member of the family of voltage-gated potassium (Kv) channel-interacting proteins, which belong to the neuronal calcium sensor family of proteins. Members of this family are small calcium binding proteins containing EF-hand-like domains. They are integral subunit components of native Kv4 channel complexes that may regulate A-type currents, and hence neuronal excitability, in response to changes in intracellular calcium. The encoded protein also functions as a calcium-regulated transcriptional repressor, and interacts with presenilins. In addition, the protein has been shown to transcriptionally repress A20 (TNFAIP3) expression and thus modulate the anti-inflammatory signaling. Alternatively spliced transcript variants encoding different isoforms have been described. Interactions Calsenilin has been shown to interact with PSEN1 and PSEN2 Presenilin-2 is a protein that ( ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CIB1
Calcium and integrin-binding protein 1 is a protein that in humans is encoded by the ''CIB1'' gene. The protein encoded by this gene is a member of the calcium-binding protein family. The specific function of this protein has not yet been determined; however this protein is known to interact with DNA-dependent protein kinase and may play a role in kinase-phosphatase regulation of DNA end-joining. This protein also interacts with integrin alpha(IIb)beta(3), which may implicate this protein as a regulatory molecule for alpha(IIb)beta(3). Interactions CIB1 has been shown to interact with RAC3, PSEN2, DNA-PKcs, UBR5 and CD61 Integrin beta-3 (β3) or CD61 is a protein that in humans is encoded by the ''ITGB3'' gene. CD61 is a cluster of differentiation found on thrombocytes. Structure and function The ITGB3 protein product is the integrin beta chain beta 3. Integrins .... References Further reading * * * * * * * * * * * * * * * * * * External links * EF-hand-containin ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
CAPN1
Calpain-1 catalytic subunit (CANP 1) is a protein that in humans is encoded by the ''CAPN1'' gene. Function The calpains, calcium-activated neutral proteases, are nonlysosomal, intracellular cysteine proteases. The mammalian calpains include ubiquitous, stomach-specific, and muscle-specific proteins. The ubiquitous enzymes consist of heterodimers with distinct large, catalytic subunits associated with a common small, regulatory subunit. This gene encodes the large subunit of the ubiquitous enzyme, calpain 1. Interactions CAPN1 has been shown to interact with PSEN2. References Further reading * * * * * * * * * * * * * * * * * External links * The MEROPS MEROPS is an online database for peptidases (also known as proteases, proteinases and proteolytic enzymes) and their inhibitors. The classification scheme for peptidases was published by Rawlings & Barrett in 1993, and that for protein inhibitor ... online database for peptidases and their inhi ... [...More Info...] [...Related Items...] OR: [Wikipedia] [Google] [Baidu] |
