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https://en.wikipedia.org/wiki/CDC73 | Cell division cycle 73, Paf1/RNA polymerase II complex component, homolog (S. cerevisiae), also known as CDC73 and parafibromin, is a protein which in humans is encoded by the CDC73 gene.
Function
Parafibromin, LEO1, PAF1, and CTR9 form the PAF protein complex, which associates with the RNA polymerase II subunit POLR2A and with a histone methyltransferase complex.
Clinical significance
Mutations in the CDC73 gene are associated with hyperparathyroidism-jaw tumor syndrome (HPT-JT) and parathyroid carcinomas.
See also
Primary hyperparathyroidism
Osteitis fibrosa cystica
References
External links
GeneReviews/NCBI/NIH/UW entry on CDC73-Related Disorders
Further reading |
https://en.wikipedia.org/wiki/Golgin%20subfamily%20A%20member%202 | Golgin subfamily A member 2, also known as 130 kDa cis-Golgi matrix protein 1 (GM130) is a protein that in humans is encoded by the GOLGA2 gene.
Function
The Golgi apparatus, which participates in glycosylation and transport of proteins and lipids in the secretory pathway, consists of a series of stacked cisternae (flattened membrane sacs). Interactions between the Golgi and microtubules are thought to be important for the reorganization of the Golgi after it fragments during mitosis. The golgins are a family of proteins, of which the protein encoded by this gene is a member, that are localized to the Golgi. This encoded protein has been postulated to play roles in the stacking of Golgi cisternae and in vesicular transport. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of these variants has not been determined.
A patient with a neuromuscular disorder has been identified that is homozygous for a deletion mutation in this gene, and morpholino knockdown in zebrafish has shown similar phenotypes.
Interactions
GOLGA2 has been shown to interact with:
GORASP1,
GORASP2,
RAB1A,
RAB1B and
RAB2A.
WAC protein
References
Further reading |
https://en.wikipedia.org/wiki/HSD3B2 | HSD3B2 is a human gene that encodes for 3beta-hydroxysteroid dehydrogenase/delta(5)-delta(4)isomerase type II or hydroxy-delta-5-steroid dehydrogenase, 3 beta- and steroid delta-isomerase 2. It is expressed principally in steroidogenic tissues and is essential for steroid hormone production. A notable exception is the placenta, where HSD3B1 is critical for progesterone production by this tissue.
Mutations in the HSD3B2 gene result in the condition congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency.
References
Further reading |
https://en.wikipedia.org/wiki/Myocilin | Myocilin, trabecular meshwork inducible glucocorticoid response (TIGR), also known as MYOC, is a protein which in humans is encoded by the MYOC gene. Mutations in MYOC are a major cause of glaucoma.
Gene location
The cytogenetic location of human MYOC gene is on the long (q) arm of chromosome 1, specifically at position 24.3 (1q24.3). The gene's molecular location starts at 171,635,417 bp and ends at 171,652,63 bp on chromosome 1 (Annotation: GRCh38.p12) (assembly).
Protein characteristics
Myocilin is a protein with a weight of 55 kDa (504 amino acid) and an overall acidic property, the product of the first gene that has been linked to Primary Open Angle Glaucoma (POAG).
Protein structure
The protein is made up of the two folding domains, the leucine zipper-like domain at the N-terminal and an olfactomedin-like domain at the C-terminal. The domain at the N-terminal is known to have 77.6% homology to the myosin heavy chain of Dictyostelium discoideum and 25% homology with the cardiac β-myosin heavy chain. The gene encodes three different exons, each consisting of different structural and functional domains.
The N-terminal is encoded by exon 1 and contains the leucine zipper structural motif, which consists of 50 amino acid residues (117-169 amino acids). The motif is found on an α-helix, which enhances the binding of the protein. The name of the domain arises due to the occurrence of leucine as well as, arginine repeats periodically on the α-helix. The leucine zipper d |
https://en.wikipedia.org/wiki/PPP2R1A | Serine/threonine-protein phosphatase 2A 65 kDa regulatory subunit A alpha isoform is an enzyme that in humans is encoded by the PPP2R1A gene. In the plant Arabidopsis thaliana a similar enzyme is encoded by the RCN1 gene (At1g25490).
Function
This gene encodes a constant regulatory subunit of protein phosphatase 2. Protein phosphatase 2 is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The constant regulatory subunit A serves as a scaffolding molecule to coordinate the assembly of the catalytic subunit and a variable regulatory B subunit. This gene encodes an alpha isoform of the constant regulatory subunit A.
Interactions
PPP2R1A has been shown to interact with:
CTTNBP2NL,
FAM40A,
PPP2CB, PPP2CA, PPP4C,
PPP2R2A,
PPP2R3B,
PPP2R5A.
STK24,
STRN, and
STRN3.
Arabidopsis RCN1
RCN1 At1g25490 is one of three genes in Arabidopsis encoding Phosphoprotein Phosphatase 2A Regulatory Subunit A (PP2Aa). The association of different b subunits with a PP2Aa-PP2ac dimer is believed to determine substrate specificity.
References
Further reading |
https://en.wikipedia.org/wiki/PSMD13 | 26S proteasome non-ATPase regulatory subunit 13 is an enzyme that in humans is encoded by the PSMD13 gene.
Function
The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a non-ATPase subunit of the 19S regulator. Two transcripts encoding different isoforms have been described.
Clinical significance
The proteasome and its subunits are of clinical significance for at least two reasons: (1) a compromised complex assembly or a dysfunctional proteasome can be associated with the underlying pathophysiology of specific diseases, and (2) they can be exploited as drug targets for therapeutic interventions. More recently, more effort has been made to consider the proteasome for the development of novel diagnostic markers and strategies. An improved and comprehensive understanding of the pathop |
https://en.wikipedia.org/wiki/RAB3A | Ras-related protein Rab-3A is a protein that in humans is encoded by the RAB3A gene. It is involved in calcium-triggered exocytosis in neurons.
Interactions
RAB3A has been shown to interact with:
RIMS1,
UNC13A,
RPH3A, and
CHM.
References
Further reading |
https://en.wikipedia.org/wiki/RAB4A | Ras-related protein Rab-4A is a protein that in humans is encoded by the RAB4A gene.
Interactions
RAB4A has been shown to interact with:
CD2AP,
KIF3B,
RAB11FIP1,
RABEP1, and
STX4.
References
Further reading |
https://en.wikipedia.org/wiki/NME1 | Nucleoside diphosphate kinase A is an enzyme that in humans is encoded by the NME1 gene. It is thought to be a metastasis suppressor.
Function
This gene (NME1) was identified because of its reduced mRNA transcript levels in highly metastatic cells. Nucleoside diphosphate kinase (NDK) exists as a hexamer composed of 'A' (encoded by this gene) and 'B' (encoded by NME2) isoforms. Mutations in this gene have been identified in aggressive neuroblastomas. Two transcript variants encoding different isoforms have been found for this gene. Co-transcription of this gene and the neighboring downstream gene (NME2) generates naturally occurring transcripts (NME1-NME2), which encodes a fusion protein consisting of sequence sharing identity with each individual gene product.
A bioinformatics study published in 2023 suggested that the NME1 gene might have a prognostic role in neuroblastoma.
Interactions
NME1 has been shown to interact with:
Aurora A kinase,
CD29
NME3,
Protein SET,
RAR-related orphan receptor alpha,
RAR-related orphan receptor beta, and
TERF1.
See also
Nucleoside-diphosphate kinase
References
Further reading |
https://en.wikipedia.org/wiki/EEF1D | Elongation factor 1-delta is a protein that in humans is encoded by the EEF1D gene.
Function
This gene encodes a subunit of the elongation factor-1 complex, which is responsible for the enzymatic delivery of aminoacyl tRNAs to the ribosome. This subunit functions as guanine nucleotide exchange factor. It is reported that this subunit interacts with HIV-1 Tat, and thus it represses the translation of host-cell, but not HIV-1, mRNAs. Several alternatively spliced transcript variants have been found for this gene, however, the full length nature of only two variants has been determined.
Interactions
EEF1D has been shown to interact with Glycyl-tRNA synthetase, EEF1G and KTN1, and is predicted to interact with TMEM63A.
References
Further reading |
https://en.wikipedia.org/wiki/Gamma-aminobutyric%20acid%20receptor%20subunit%20alpha-1 | Gamma-aminobutyric acid receptor subunit alpha-1 is a protein that in humans is encoded by the GABRA1 gene.
GABA is the major inhibitory neurotransmitter in the mammalian brain where it acts at GABA-A receptors, which are ligand-gated chloride channels. Chloride conductance of these channels can be modulated by agents such as benzodiazepines that bind to the GABA-A receptor. At least 16 distinct subunits of GABA-A receptors have been identified.
The GABRA1 receptor is the specific target of the z-drug class of nonbenzodiazepine hypnotic agents and is responsible for their hypnotic and hallucinogenic effects.
See also
GABAA receptor
References
Further reading
Ion channels |
https://en.wikipedia.org/wiki/ELOB | Elongin B is a protein that in humans is encoded by the ELOB gene.
Function
Elongin B is a subunit of the transcription factor B (SIII) complex. The SIII complex is composed of elongins A/A2, B and C. It activates elongation by RNA polymerase II by suppressing transient pausing of the polymerase at many sites within transcription units. Elongin A functions as the transcriptionally active component of the SIII complex, whereas elongins B and C are regulatory subunits. Elongin A2 is specifically expressed in the testis, and capable of forming a stable complex with elongins B and C. The von Hippel-Lindau tumor suppressor protein binds to elongins B and C, and thereby inhibits transcription elongation. Two alternatively spliced transcript variants encoding different isoforms have been described for this gene.
Interactions
TCEB2 has been shown to interact with:
CUL2,
TCEB1, and
Von Hippel-Lindau tumor suppressor.
References
Further reading
External links
PDBe-KB provides an overview of all the structure information available in the PDB for Human Elongin-B |
https://en.wikipedia.org/wiki/T-cell%20lymphoma%20invasion%20and%20metastasis-inducing%20protein%201 | Rho guanine nucleotide exchange factor TIAM1 is a protein that in humans is encoded by the TIAM1 gene.
Structure
TIAM1 is tightly associate with BAIAP2 as a subunit. It contains one DH (DBL-homology) domain, one PDZ domain, two PH domains and one Ras-binding RBD domain.
Function
TIAM1 modulates the activity of Rho GTP-binding proteins and connects extracellular signals to cytoskeletal activities. In addition, TIAM1 activates Rac1, CDC42, and to a lesser extent RhoA.
Clinical significance
TIAM1 is found in virtually all tumor cell lines examined including B- and T-lymphomas, neuroblastomas, melanomas and carcinomas.
Interactions
T-cell lymphoma invasion and metastasis-inducing protein 1 has been shown to interact with ANK1, Myc, RAC1 and PPP1R9B.
Tiam1 interacts also with para-cingulin, that plays a role in recruiting Tiam1 to junctions and thus activate Rac1 at epithelial junctions.
References
Further reading
Peripheral membrane proteins |
https://en.wikipedia.org/wiki/NPHS2 | Podocin is a protein that in humans is encoded by the NPHS2 gene.
Interactions
NPHS2 has been shown to interact with Nephrin and CD2AP.
See also
Focal segmental glomerulosclerosis
References
Further reading |
https://en.wikipedia.org/wiki/NOS1 | Nitric oxide synthase 1 (neuronal), also known as NOS1, is an enzyme that in humans is encoded by the NOS1 gene.
Function
Nitric oxide synthases () (NOSs) are a family of synthases that catalyze the production of nitric oxide (NO) from L-arginine. NO is a chemical messenger with diverse functions throughout the body depending on its enzymatic source and tissue localization. In the brain and peripheral nervous system, where NOS1 is largely present, NO displays many properties of a neurotransmitter and may be involved in long term potentiation. It is implicated in neurotoxicity associated with stroke and neurodegenerative diseases, neural regulation of smooth muscle, including peristalsis and sphincter relaxation, and penile erection. NO is also responsible for endothelium-derived relaxing factor activity regulating blood pressure as produced from its related enzyme NOS3. In macrophages, NO mediates tumoricidal and bactericidal actions, as produced from its related enzyme NOS2. Various pharmacological inhibitors of NO synthases (NOS) block these effects, but further distinction of their function has been elucidated by animal models in which these specific genes have been inactivated. Neuronal NOS (NOS1), Endothelial NOS (NOS3), and Inducible NOS macrophage NOS are distinct isoforms. Both the neuronal and the macrophage forms are unusual among oxidative enzymes in requiring several electron donors: flavin adenine dinucleotide (FAD), flavin mononucleotide (FMN), NADPH, and tetr |
https://en.wikipedia.org/wiki/Tight%20junction%20protein%202 | Tight junction protein ZO-2 is a protein that in humans is encoded by the TJP2 gene.
Tight junction proteins (TJPs) belong to a family of membrane-associated guanylate kinase (MAGUK) homologs that are involved in the organization of epithelial and endothelial intercellular junctions. TJPs bind to the cytoplasmic C termini of junctional transmembrane proteins and link them to the actin cytoskeleton [supplied by OMIM].
Interactions
Tight junction protein 2 has been shown to interact with tight junction protein 1, band 4.1, occludin and USP53.
References
Further reading |
https://en.wikipedia.org/wiki/LILRB1 | Leukocyte immunoglobulin-like receptor subfamily B member 1 is a protein that in humans is encoded by the LILRB1 gene.
Function
This gene is a member of the leukocyte immunoglobulin-like receptor (LIR) family, which is found in a gene cluster at chromosomal region 19q13.4. The encoded protein belongs to the subfamily B class of LIR receptors which contain two or four extracellular immunoglobulin domains, a transmembrane domain, and two to four cytoplasmic immunoreceptor tyrosine-based inhibitory motifs (ITIMs). The receptor is expressed on immune cells where it binds to MHC class I molecules on antigen-presenting cells and transduces a negative signal that inhibits stimulation of an immune response. It is thought to control inflammatory responses and cytotoxicity to help focus the immune response and limit autoreactivity. Multiple transcript variants encoding different isoforms have been found for this gene.
See also
Cluster of differentiation
References
Further reading
External links
Clusters of differentiation
Immunoglobulin superfamily |
https://en.wikipedia.org/wiki/ACP1 | Low molecular weight phosphotyrosine protein phosphatase is an enzyme that in humans is encoded by the ACP1 gene.
The product of this gene belongs to the phosphotyrosine protein phosphatase family of proteins. It functions as an acid phosphatase and a protein tyrosine phosphatase by hydrolyzing protein tyrosine phosphate to protein tyrosine and orthophosphate. This enzyme also hydrolyzes orthophosphoric monoesters to alcohol and orthophosphate. This gene is genetically polymorphic, and three common alleles segregating at the corresponding locus give rise to six phenotypes. Each allele appears to encode at least two electrophoretically different isozymes, Bf and Bs, which are produced in allele-specific ratios. Three transcript variants encoding distinct isoforms have been identified for this gene.
Clinical significance
Clinically, increased expression of ACP1 is a biomarker for poor prognosis in prostate cancer has been linked to worse clinical behaviour of prostate cancer, possibly outperforming the widely used Gleason grading system with respect to this important parameter. Also in other cancers, e.g. colon cancer, high ACP1 protein levels are linked to aggressive disease. It has been suggested that ACP1 acts as a bona fide oncogene, but for now this notion remains unproven even if ACP1 overexpression drives cells towards a Warburg effect-like glycolytic phenotype. An alternative explanation for association between ACP1 expression and cancer progression is that tumor-der |
https://en.wikipedia.org/wiki/RAPGEF1 | Rap guanine nucleotide exchange factor 1 is a protein that in humans is encoded by the RAPGEF1 gene.
Function
The protein encoded by this gene is a human guanine nucleotide releasing protein for Ras protein. It belongs to the adaptor-type Src homology (SH)2-containing molecules. Src homology 2 domains are globular protein modules present in a large variety of functionally distinct proteins. They mediate binding events that control the activity and localization of many proteins involved in the transmission of signals from the cell surface to the nucleus. The mRNAs of these proteins are expressed ubiquitously in human adult and fetal tissues. Several alternatively spliced transcript variants of this gene have been described, but the full-length nature of some variants has not been determined.
Interactions
RAPGEF1 has been shown to interact with:
BCAR1,
CRK,
CRKL
Grb2, and
HCK.
References
Further reading
External links
RAPGEF1 Info with links in the Cell Migration Gateway |
https://en.wikipedia.org/wiki/KLK2 | Kallikrein-2 is a protein that in humans is encoded by the KLK2 gene, and is particularly associated with prostatic tissue.
References
Further reading
External links
The MEROPS online database for peptidases and their inhibitors: S01.161 |
https://en.wikipedia.org/wiki/MAP3K11 | Mitogen-activated protein kinase kinase kinase 11 is an enzyme that in humans is encoded by the MAP3K11 gene.
Function
The protein encoded by this gene is called MLK3 and it is a member of the serine/threonine kinase family. This kinase contains a SH3 domain and a leucine zipper-basic motif. This kinase preferentially activates MAPK8/JNK kinase, and functions as a positive regulator of JNK signaling pathway. This kinase can directly phosphorylate, and activates JNK and p38, and is found to be involved in the transcription activity of AP1 mediated by Rho family GTPases and CDC42.
Interactions
MAP3K11 has been shown to interact with:
AKT1,
CDC42,
MAPK8IP1,
MAPK8IP2, and
SH3RF1.
References
Further reading
EC 2.7.11 |
https://en.wikipedia.org/wiki/Homeobox%20protein%20MSX-1 | Homeobox protein MSX-1, is a protein that in humans is encoded by the MSX1 gene. MSX1 transcripts are not only found in thyrotrope-derived TSH cells, but also in the TtT97 thyrotropic tumor, which is a well differentiated hyperplastic tissue that produces both TSHß- and a-subunits and is responsive to thyroid hormone. MSX1 is also expressed in highly differentiated pituitary cells which until recently was thought to be expressed exclusively during embryogenesis. There is a highly conserved structural organization of the members of the MSX family of genes and their abundant expression at sites of inductive cell–cell interactions in the embryo suggest that they have a pivotal role during early development.
Function
This gene encodes a member of the muscle segment homeobox gene family. The encoded protein functions as a transcriptional repressor during embryogenesis through interactions with components of the core transcription complex and other homeoproteins. It may also have roles in limb-pattern formation, craniofacial development, in particular, odontogenesis, and tumor growth inhibition. There is also strong evidence from sequencing studies of candidate genes involved in clefting that mutations in the MSX1 gene may be associated in the pathogenesis of cleft lip and palate. Mutations in this gene, which was once known as homeobox 7, have also been associated with Witkop syndrome, Wolf–Hirschhorn syndrome, and autosomal dominant hypodontia. Haploinsufficiency of MSX1 prote |
https://en.wikipedia.org/wiki/OAS1 | 2'-5'-oligoadenylate synthetase 1 is an enzyme that in humans is encoded by the OAS1 gene.
This gene encodes a member of the 2-5A synthetase family, which include essential proteins involved in the innate immune response to viral infection.
The encoded protein is induced by interferons and uses adenosine triphosphate in 2'-specific nucleotidyl transfer reactions to synthesize 2',5'-oligoadenylates (2-5As). These molecules activate latent RNase L, which results in both viral and endogenous RNA degradation and the inhibition of viral replication. The three known members of this gene family are located in a cluster on chromosome 12. Hypomorphic mutations in this gene have been associated with host susceptibility to viral infection, while gain-of-function variants can cause autoinflammatory immunodeficiency. Alternatively spliced transcript variants encoding different isoforms have been described.
References
Further reading |
https://en.wikipedia.org/wiki/PPP2R2B | Serine/threonine-protein phosphatase 2A 55 kDa regulatory subunit B beta isoform is an enzyme that in humans is encoded by the PPP2R2B gene.
The product of this gene belongs to the phosphatase 2regulatory subunit B family. Protein phosphatase 2 is one of the four major Ser/Thr phosphatases, and it is implicated in the negative control of cell growth and division. It consists of a common heteromeric core enzyme, which is composed of a catalytic subunit and a constant regulatory subunit, that associates with a variety of regulatory subunits. The B regulatory subunit might modulate substrate selectivity and catalytic activity. This gene encodes a beta isoform of the regulatory subunit B55 subfamily. Defects in the 5' UTR of this gene may cause a rare form of autosomal dominant spinocerebellar ataxia 12.
References
Further reading
External links
GeneReviews/NCBI/NIH/UW entry on Spinocerebellar Ataxia Type 12 |
https://en.wikipedia.org/wiki/PSMB10 | Proteasome subunit beta type-10 as known as 20S proteasome subunit beta-2i is a protein that in humans is encoded by the PSMB10 gene.
This protein has a major role in the immune system as part of an immunoproteasome that is primarily induced upon infection and formed by replacing constitutive beta subunits with inducible beta subunits which possess specific cleavage properties that aid in the release of peptides necessary for MHC class I antigen presentation. The immunoproteasome appears to have a pivotal role in modulating NFκB signaling.
Structure
Gene
This gene PSMB10 encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. Proteolytic processing is required to generate a mature subunit. Expression of this gene is induced by gamma interferon, and this gene product replaces catalytic subunit beta2 (proteasome subunit beta type-7) in the immunoproteasome.
The human PSMB10 gene has 8 exons and locates at chromosome band 16q22.1.
Protein structure
The human protein proteasome subunit beta type-8 is 25 kDa in size and composed of 234 amino acids. The calculated theoretical pI of this protein is 6.07.
Complex assembly
Proteasome subunit beta type-10 is one of the 17 essential subunits (alpha subunits 1-7, constitutive beta subunits 1-7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex. In particular, proteasome subunit beta-2i, along wit |
https://en.wikipedia.org/wiki/PTX3 | Pentraxin-related protein PTX3 also known as TNF-inducible gene 14 protein (TSG-14) is a protein that in humans is encoded by the PTX3 gene.
Pentraxin 3 (ptx3) is a member of the pentraxin superfamily. This super family characterized by cyclic multimeric structure.
PTX3 is rapidly produced and released by several cell types, in particular by mononuclear phagocytes, dendritic cells (DCs), fibroblasts and endothelial cells in response to primary inflammatory signals [e.g., toll-like receptor (TLR) engagement, TNFα, IL-1β]. PTX3 binds with high affinity to the complement component C1q, the extracellular matrix component TNFα induced protein 6 (TNFAIP6; also called TNF-stimulated gene 6, TSG-6) and selected microorganisms, including Aspergillus fumigatus and Pseudomonas aeruginosa.
PTX3 activates the classical pathway of complement activation and facilitates pathogen recognition by macrophages and DCs.
Structure
Human and murine PTX3, localized in the syntenic region of chromosome 3 (q24-28), are highly conserved, sharing 82% identical and 92% conserved amino acids. The human PTX3 gene is organized into three exons coding for the leader peptide (which is cleaved from the mature protein), the amino-terminal domain and the pentraxin domain of the protein.
The transcribed PTX3 protein is 381 amino acids long, has a predicted molecular weight of 40,165 Da and consists of a carboxy-terminal 203 amino acid long pentraxin domain coupled with an amino-terminal 178 amino acid long do |
https://en.wikipedia.org/wiki/C1QA | Complement C1q subcomponent subunit A is a protein that in humans is encoded by the C1QA gene.
This gene encodes a major constituent of the human complement system subcomponent C1q.
C1q associates with C1r and C1s in order to yield the first component of the serum complement system. Deficiency of C1q has been associated with lupus erythematosus and glomerulonephritis. C1q is composed of 18 polypeptide chains: six A-chains, six B-chains, and six C-chains. Each chain contains a collagen-like region located near the N terminus and a C-terminal globular region. The A-, B-, and C-chains are arranged in the order A-C-B on chromosome 1. This gene encodes the A-chain polypeptide of human complement subcomponent C1q.
References
External links
Further reading |
https://en.wikipedia.org/wiki/CALM2 | Calmodulin 2 is a protein that in humans is encoded by the CALM2 gene. A member of the calmodulin family of signaling molecules, it is an intermediary between calcium ions, which act as a second messenger, and many intracellular processes, such as the contraction of cardiac muscle.
Clinical significance
Mutations in CALM2 are associated with cardiac arrhythmias. In particular, several single-nucleotide polymorphisms of CALM2 have been reported as potential causes of sudden infant death syndrome. Due to their heritability, CALM2 mutations can affect multiple children in a family, and the discovery of the deadly consequences of these mutations has led to challenges against the murder convictions of mothers of multiple deceased infants, as in the case of Kathleen Folbigg in Australia.
Interactions
CALM2 has been shown to interact with AKAP9.
References
External links
Further reading
EF-hand-containing proteins |
https://en.wikipedia.org/wiki/CBLB%20%28gene%29 | CBL-B is an E3 ubiquitin-protein ligase that in humans is encoded by the CBLB gene. CBLB is a member of the CBL gene family.
Function
CBL-B functions as a negative regulator of T-cell activation. CBL-B expression in T cells causes ligand-induced T cell receptor down-modulation, controlling the activation degree of T cells during antigen presentation.
Clinical significance
Mutation of the CBLB gene has been associated with autoimmune conditions such as type 1 diabetes.
Interactions
CBLB has been shown to interact with:
CRKL,
Epidermal growth factor receptor,
Grb2,
NEDD4,
PIK3R1, and
SH3KBP1.
References
External links
Further reading |
https://en.wikipedia.org/wiki/CLCN5 | The CLCN5 gene encodes the chloride channel Cl-/H+ exchanger ClC-5. ClC-5 is mainly expressed in the kidney, in particular in proximal tubules where it participates to the uptake of albumin and low-molecular-weight proteins, which is one of the principal physiological role of proximal tubular cells. Mutations in the CLCN5 gene cause an X-linked recessive nephropathy named Dent disease (Dent disease 1 MIM#300009) characterized by excessive urinary loss of low-molecular-weight proteins and of calcium (hypercalciuria), nephrocalcinosis (presence of calcium phosphate aggregates in the tubular lumen and/or interstitium) and nephrolithiasis (kidney stones).
The CLCN5 gene
Structure
The human CLCN5 gene (MIM#300008, reference sequence NG_007159.2) is localized in the pericentromeric region on chromosome Xp11.23. It extends over about 170 Kb of genomic DNA, has a coding region of 2,238 bp and consists of 17 exons including 11 coding exons (from 2 to 12). The CLCN5 gene has 8 paralogues (CLCN1, CLCN2, CLCN3, CLCN4, CLCN6, CLCN7, CLCNKA, CLCNKB) and 201 orthologues among jawed vertebrates (Gnathostomata).
Five different CLCN5 gene transcripts have been discovered, two of which (transcript variants 3 [NM_000084.5] and 4 [NM_001282163.1]) encode for the canonical 746 amino acid protein, two (transcript variants 1 [NM_001127899.3] and 2 [NM_001127898.3]) for the NH2-terminal extended 816 amino acid protein and one does not encode for any protein (Transcript variant 5, [NM_001272102.2]) |
https://en.wikipedia.org/wiki/RAD23A | UV excision repair protein RAD23 homolog A is a protein that in humans is encoded by the RAD23A gene.
Function
The protein encoded by this gene is one of two human homologs of Saccharomyces cerevisiae Rad23, a protein involved in nucleotide excision repair (NER). This protein was shown to interact with, and elevate the nucleotide excision activity of 3-methyladenine-DNA glycosylase (MPG), which suggested a role in DNA damage recognition in base excision repair. This protein contains an N-terminal ubiquitin-like domain, which was reported to interact with 26S proteasome, as well as with ubiquitin protein ligase E6AP, and thus suggests that this protein may be involved in the ubiquitin mediated proteolytic pathway in cells.
Interactions
RAD23A has been shown to interact with:
Ataxin 3,
PSMD4, and
Sequestosome 1.
References
Further reading
External links
Human proteins |
https://en.wikipedia.org/wiki/RHEB | RHEB also known as Ras homolog enriched in brain (RHEB) is a GTP-binding protein that is ubiquitously expressed in humans and other mammals. The protein is largely involved in the mTOR pathway and the regulation of the cell cycle.
RHEB is a recently discovered member of the Ras superfamily. Being a relative of Ras, the overexpression of RHEB can be seen in multiple human carcinomas. For this reason, ways to inhibit RHEB to control the mTOR pathway are studied as possible treatments for uncontrollable tumor cell growth in several diseases, especially in tuberous sclerosis.
Structure
Rheb is a 21 kDa protein monomer composed of 184 amino acids. The first 169 amino acids by the N-terminus make up the GTPase domain, and the remaining amino acids are part of a hypervariable region ending at the C-terminus in a CAAX motif (C – cysteine, A – aliphatic amino acid, X – C-terminus amino acid).
The protein is a lipid-anchored, cell-membrane protein with five repeats of the RAS-related GTP-binding region. Also present are “switch” regions, I and II, which undergo conformational changes when shuttling between GTP-bound(activated) and GDP-bound(inactive) forms.
RHEB is expressed by the RHEB gene in humans. Three pseudogenes have been mapped, two on chromosome 10 and one on chromosome 22.
Function
Activation of mTORC1
RHEB is vital in regulation of growth and cell cycle progression due to its role in the insulin/TOR/S6K signaling pathway. Mechanistic Target of Rapamycin Complex 1 |
https://en.wikipedia.org/wiki/The%20Power%20%28album%29 | The Power is the debut studio album by Australian pop singer Vanessa Amorosi. It was released on 3 April 2000 on CBK Produktions and Transistor Music Australia. The album debuted at number 1 on the Australian Albums Chart and was certified 4× platinum by the Australian Recording Industry Association (ARIA). An international version was released with different album art and track listing.
Critical reception
AllMusic editor Brendan Swift called The Power a "solid debut release." He found that the album has her flexing "impressive vocals among a range of standard pop, dance, and rock tracks. Her strong and soulful voice doesn't always sound at home among the more lightweight pop [...] The Power is characterized by consistency rather than standout songs – a glimpse of Vanessa Amorosi's promise, rather than the best of Vanessa Amorosi." Irene Kanaris of Melbourne radio station 3FOX-FM called the album "one of the best" Australian pop album in years. Jodie Prudames from MTV Australia found that The Power was "fresh and shows off her great voice."
Accolades
At the ARIA Music Awards of 2000, the album was nominated for two awards: Highest Selling Album and Breakthrough Release.
Track listing
Charts
Weekly charts
Year-end charts
Decade-end charts
Certifications
Release history
See also
List of number-one albums of 2000 (Australia)
List of top 25 albums for 2000 in Australia
References
Vanessa Amorosi albums
2000 debut albums
Pop albums by Australian artists |
https://en.wikipedia.org/wiki/Acidic%20leucine-rich%20nuclear%20phosphoprotein%2032%20family%20member%20A | Acidic leucine-rich nuclear phosphoprotein 32 family member A is a protein that in humans is encoded by the ANP32A gene. It is one of the targets of an oncomiR, MIRN21.
Interactions
Acidic leucine-rich nuclear phosphoprotein 32 family member A has been shown to interact with MAP1B, TAF1A and Protein SET.
See also
ANP32B, ANP32C, ANP32D, ANP32E
References
Further reading
External links |
https://en.wikipedia.org/wiki/NRIP1 | Nuclear receptor-interacting protein 1 (NRIP1) also known as receptor-interacting protein 140 (RIP140) is a protein that in humans is encoded by the NRIP1 gene.
Function
Nuclear receptor interacting protein 1 (NRIP1) is a nuclear protein that specifically interacts with the hormone-dependent activation domain AF2 of nuclear receptors. Also known as RIP140, this protein is a key regulator which modulates transcriptional activity of a variety of transcription factors, including the estrogen receptor.
RIP140 has an important role in regulating lipid and glucose metabolism, and regulates gene expression in metabolic tissues including heart, skeletal muscle, and liver. A major role for RIP140 in adipose tissue is to block the expression of genes involved in energy dissipation and mitochondrial uncoupling, including uncoupling protein 1 and carnitine palmitoyltransferase 1b.
Estrogen-related receptor alpha (ERRa) can activate RIP140 during adipogenesis, by means of directly binding to an estrogen receptor element/ERR element and indirectly through Sp1 binding to the proximal promoter.
RIP140 suppresses the expression of mitochondrial proteins succinate dehydrogenase complex b and CoxVb and acts as a negative regulator of glucose uptake in mice.
Knockout studies
Knockout mice that completely lack the RIP140 molecule are lean and stay lean, even on a rich diet.
Knockout mice (females) are also infertile because they fail to ovulate. Failure of ovulation in these mice is ca |
https://en.wikipedia.org/wiki/PICK1 | Protein Interacting with C Kinase - 1 is a protein that in humans is encoded by the PICK1 gene.
Function
The protein encoded by this gene contains a PDZ domain, through which it interacts with protein kinase C, alpha (PRKCA). This protein may function as an adaptor that binds to and organizes the subcellular localization of a variety of membrane proteins. It has been shown to interact with multiple glutamate receptor subtypes, monoamine plasma membrane transporters, as well as non-voltage gated sodium channels, and may target PRKCA to these membrane proteins and thus regulate their distribution and function. This protein has also been found to act as an anchoring protein that specifically targets PRKCA to mitochondria in a ligand-specific manner. Three transcript variants encoding the same protein have been found for this gene.
Interactions
PICK1 has been shown to interact with:
ACCN2,
BNC1,
Dopamine transporter,
GRIA2,
GRIA3,
GRIA4,
GRIK1,
GRIK2,
GRIK3,
HER2/neu,
Metabotropic glutamate receptor 3, and
Metabotropic glutamate receptor 7.
References
Further reading
External links
Genecards
MGI |
https://en.wikipedia.org/wiki/RBM8A | RNA-binding protein 8A is a protein that in humans is encoded by the RBM8A gene.
This gene encodes a protein with a conserved RNA-binding motif. The protein is found predominantly in the nucleus, although it is also present in the cytoplasm. It is preferentially associated with mRNAs produced by splicing, including both nuclear mRNAs and newly exported cytoplasmic mRNAs. It is thought that the protein remains associated with spliced mRNAs as a tag to indicate where introns had been present, thus coupling pre- and post-mRNA splicing events. Previously, it was thought that two genes encode this protein, RBM8A and RBM8B; it is now thought that the RBM8B locus is a pseudogene. Two alternative start codons result in two forms of the protein, and this gene also uses multiple polyadenylation sites.
Interactions
RBM8A has been shown to interact with IPO13, MAGOH and UPF3A.
Related gene problems
TAR syndrome
1q21.1 deletion syndrome
1q21.1 duplication syndrome
References
Further reading |
https://en.wikipedia.org/wiki/HDAC6 | Histone deacetylase 6 is an enzyme that in humans is encoded by the HDAC6 gene. HDAC6 has emerged as a highly promising candidate to selectively inhibit as a therapeutic strategy to combat several types of cancer and neurodegenerative disorders.
Function
Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromatin structure and affects transcription. The protein encoded by this gene belongs to class II of the histone deacetylase/acuc/apha family. It contains an internal duplication of two catalytic domains that appear to function independently of each other. This protein possesses histone deacetylase activity and represses transcription.
It retracts the cilium of the cell, which is necessary prior to mitosis.
HDAC encourages cell motility and catalyzes α-tubulin deacetylation. As a result the enzyme encourages cancer cell metastasis.
HDAC6 affects transcription and translation by regulating heat-shock protein 90 (Hsp90).
HDAC6 is required in the formation of stress granule (SG) proteins and is instrumental in SG formation; pharmacological inhibition or genetic removal of HDAC6 abolished SG formation.
HDAC6 bonds with high affinity to ubiquitinated proteins.
HDAC6 is involved in leptin sensitivity.
HDAC6 deacetylates tyrosine residue T178 on TAK1.
Clinical relevance
Mutations in this gene have been associated to Alzheimer's disease.
Over expression of this protein |
https://en.wikipedia.org/wiki/Delta-aminolevulinic%20acid%20dehydratase | Aminolevulinic acid dehydratase (porphobilinogen synthase, or ALA dehydratase, or aminolevulinate dehydratase) is an enzyme () that in humans is encoded by the ALAD gene. Porphobilinogen synthase (or ALA dehydratase, or aminolevulinate dehydratase) synthesizes porphobilinogen through the asymmetric condensation of two molecules of aminolevulinic acid. All natural tetrapyrroles, including hemes, chlorophylls and vitamin B12, share porphobilinogen as a common precursor. Porphobilinogen synthase is the prototype morpheein.
Function
It catalyzes the following reaction, the second step of the biosynthesis of porphyrin:
2 5-Aminolevulinic acid porphobilinogen + 2 H2O
It therefore catalyzes the condensation of 2 molecules of 5-aminolevulinate to form porphobilinogen (a precursor of heme, cytochromes and other hemoproteins). This reaction is the first common step in the biosynthesis of all biological tetrapyrroles. Zinc is essential for enzymatic activity.
Structure
The structural basis for allosteric regulation of Porphobilinogen synthase (PBGS) is modulation of a quaternary structure equilibrium between octamer and hexamer (via dimers), which is represented schematically as 6mer* ↔ 2mer* ↔ 2mer ↔ 8mer. The * represents a reorientation between two domains of each subunit that occurs in the dissociated state because it is sterically forbidden in the larger multimers.
PBGS is encoded by a single gene and each PBGS multimer is composed of multiple copies of the same protein. Ea |
https://en.wikipedia.org/wiki/C-C%20chemokine%20receptor%20type%206 | Chemokine receptor 6 also known as CCR6 is a CC chemokine receptor protein which in humans is encoded by the CCR6 gene. CCR6 has also recently been designated CD196 (cluster of differentiation 196). The gene is located on the long arm of Chromosome 6 (6q27) on the Watson (plus) strand. It is 139,737 bases long and encodes a protein of 374 amino acids (molecular weight 42,494 Da).
Function
This protein belongs to family A of G protein-coupled receptor superfamily. The gene is expressed in lymphatic and non-lymphatic tissue as spleen, lymph nodes, pancreas, colon, appendix, small intestine. CCR6 is expressed on B-cells, immature dendritic cells (DC), T-cells (Th1, Th2, Th17, Treg), natural killer T cells (NKT cells) and neutrophils. The ligand of this receptor is CCL20 or in the other name - macrophage inflammatory protein 3 alpha (MIP-3 alpha). This chemokine receptor is special because it binds only one chemokine ligand CCL20 in compare to other chemokine receptors. CCR6 has a key role in connection between immature DC an adaptive immunity. This receptor has been shown to be important for B-lineage maturation and antigen-driven B-cell differentiation, and it may regulate the migration and recruitment of dendritic cells and T cells during inflammatory and immunological responses. Alternatively spliced transcript variants that encode the same protein have been described for this gene.
Interleukin 4 (IL-4) and interferon gamma (IFNγ) suppress expression of CCR6 in langerhan |
https://en.wikipedia.org/wiki/Formyl%20peptide%20receptor%202 | N-formyl peptide receptor 2 (FPR2) is a G-protein coupled receptor (GPCR) located on the surface of many cell types of various animal species. The human receptor protein is encoded by the FPR2 gene and is activated to regulate cell function by binding any one of a wide variety of ligands including not only certain N-Formylmethionine-containing oligopeptides such as N-Formylmethionine-leucyl-phenylalanine (FMLP) but also the polyunsaturated fatty acid metabolite of arachidonic acid, lipoxin A4 (LXA4). Because of its interaction with lipoxin A4, FPR2 is also commonly named the ALX/FPR2 or just ALX receptor.
Expression
The FPR2 receptor is expressed on human neutrophils, eosinophils, monocytes, macrophages, T cells, synovial fibroblasts, and intestinal and airway epithelium.
Function
Many oligopeptides that possess an N-Formylmethionine N-terminal residue such as the prototypical tripeptide N-Formylmethionine-leucyl-phenylalanine (i.e. FMLP), are products of the protein synthesis conducted by bacteria. They stimulate granulocytes to migrate directionally (see chemotaxis) and become active in engulfing (see phagocytosis) and killing bacteria and thereby contribute to host defense by directing the innate immune response of acute inflammation to sites of bacterial invasion. Early studies suggested that these formyl oligopeptides operated by a Receptor (biochemistry) mechanism. Accordingly, the human leukocyte cell line, HL-60 promyelocytes (which do not respond to FMLP), |
https://en.wikipedia.org/wiki/GABRB3 | Gamma-aminobutyric acid receptor subunit beta-3 is a protein that in humans is encoded by the GABRB3 gene. It is located within the 15q12 region in the human genome and spans 250kb. This gene includes 10 exons within its coding region. Due to alternative splicing, the gene codes for many protein isoforms, all being subunits in the GABAA receptor, a ligand-gated ion channel. The beta-3 subunit is expressed at different levels within the cerebral cortex, hippocampus, cerebellum, thalamus, olivary body and piriform cortex of the brain at different points of development and maturity. GABRB3 deficiencies are implicated in many human neurodevelopmental disorders and syndromes such as Angelman syndrome, Prader-Willi syndrome, nonsyndromic orofacial clefts, epilepsy and autism. The effects of methaqualone and etomidate are mediated through GABBR3 positive allosteric modulation.
Gene
The GABRB3 gene is located on the long arm of chromosome 15, within the q12 region in the human genome. It is located in a gene cluster, with two other genes, GABRG3 and GABRA5. GABRB3 was the first gene to be mapped to this particular region. It spans approximately 250kb and includes 10 exons within its coding region, as well as two additional alternative first exons that encode for signaling peptides. Alternatively spliced transcript variants encoding isoforms with distinct signal peptides have been described. This gene is located within an imprinting region that spans the 15q11-13 region. Its sequenc |
https://en.wikipedia.org/wiki/Lactate%20dehydrogenase%20A | Lactate dehydrogenase A (LDHA) is an enzyme which in humans is encoded by the LDHA gene. It is a monomer of Lactate dehydrogenase, which exists as a tetramer. The other main subunit is lactate dehydrogenase B (LDHB).
Function
Lactate dehydrogenase A catalyzes the inter-conversion of pyruvate and L-lactate with concomitant inter-conversion of NADH and NAD+. LDHA is found in most somatic tissues, though predominantly in muscle tissue and tumors, and belongs to the lactate dehydrogenase family. It has long been known that many human cancers have higher LDHA levels compared to normal tissues. It has also been shown that LDHA plays an important role in the development, invasion and metastasis of malignancies. Mutations in LDHA have been linked to exertional myoglobinuria.
Interactive pathway map
Model organisms
Model organisms have been used in the study of LDHA function. A conditional knockout mouse line, called Ldhatm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty seven tests were carried out on mutant mice and five significant abnormalities were observed. Few homozygous mutant embryos were identified during gestation, and none survived until weaning. The remaining tests were carried out on hetero |
https://en.wikipedia.org/wiki/HSPB8 | Heat shock protein beta-8 is a protein that in humans is encoded by the HSPB8 gene.
Interactions
HSPB8 has been shown to interact with:
HSPB2, and
Hsp27.
Clinical importance
Mutations in this gene have been associated with an autosomal dominant rimmed vacuolar myopathy The clinical features of this condition are distal and proximal myopathy. MRI show severe relatively symmetric multifocal fatty degenerative changes within the muscles. Muscle biopsy shows rimmed vacuoles, muscle fiber atrophy and endomysial fibrosis.
References
Further reading
External links
GeneReviews/NCBI/NIH/UW entry on Charcot-Marie-Tooth Neuropathy Type 2 |
https://en.wikipedia.org/wiki/PCSK9 | Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme encoded by the PCSK9 gene in humans on chromosome 1. It is the 9th member of the proprotein convertase family of proteins that activate other proteins. Similar genes (orthologs) are found across many species. As with many proteins, PCSK9 is inactive when first synthesized, because a section of peptide chains blocks their activity; proprotein convertases remove that section to activate the enzyme. The PCSK9 gene also contains one of 27 loci associated with increased risk of coronary artery disease.
PCSK9 is ubiquitously expressed in many tissues and cell types. PCSK9 binds to and degrades the receptor for low-density lipoprotein particles (LDL), which typically transport 3,000 to 6,000 fat molecules (including cholesterol) per particle, within extracellular fluid. The LDL receptor (LDLR), on liver and other cell membranes, binds and initiates ingestion of LDL-particles from extracellular fluid into cells and targets the complex to lysosomes for destruction. If PCSK9 is blocked, the LDL-LDLR complex separates during trafficking, with the LDL digested in the lysosome, but the LDLRs instead recycled back to the cell surface and so able to remove additional LDL-particles from the extracellular fluid. Therefore, blocking PCSK9 can lower blood LDL-particle concentrations.
PCSK9 has medical importance because it acts in lipoprotein homeostasis. Agents that block PCSK9 can lower LDL particle concentrations. The first |
https://en.wikipedia.org/wiki/LIG4 | DNA ligase 4 is an enzyme that in humans is encoded by the LIG4 gene.
Function
The protein encoded by this gene is an ATP-dependent DNA ligase that joins double-strand breaks during the non-homologous end joining pathway of double-strand break repair. It is also essential for V(D)J recombination. Lig4 forms a complex with XRCC4, and further interacts with the DNA-dependent protein kinase (DNA-PK) and XLF/Cernunnos, which are also required for NHEJ. The crystal structure of the Lig4/XRCC4 complex has been resolved. Defects in this gene are the cause of LIG4 syndrome. The yeast homolog of Lig4 is Dnl4.
LIG4 Syndrome
In humans, deficiency of DNA ligase 4 results in a clinical condition known as LIG4 syndrome. This syndrome is characterized by cellular radiation sensitivity, growth retardation, developmental delay, microcephaly, facial dysmorphisms, increased disposition to leukemia, variable degrees of immunodeficiency and reduced number of blood cells.
Haematopoietic stem cell aging
Accumulation of DNA damage leading to stem cell exhaustion is regarded as an important aspect of aging. Deficiency of lig4 in pluripotent stem cells impairs Non-homologous end joining (NHEJ) and results in accumulation of DNA double-strand breaks and enhanced apoptosis. Lig4 deficiency in the mouse causes a progressive loss of haematopoietic stem cells and bone marrow cellularity during aging. The sensitivity of haematopoietic stem cells to lig4 deficiency suggests that lig4-mediated NH |
https://en.wikipedia.org/wiki/MAP4 | Microtubule-associated protein 4 is a protein that in humans is encoded by the MAP4 gene.
The protein encoded by this gene is a major non-neuronal microtubule-associated protein. This protein contains a domain similar to the microtubule-binding domains of neuronal microtubule-associated protein (MAP2) and microtubule-associated protein tau (MAPT/TAU). This protein promotes microtubule assembly, and has been shown to counteract destabilization of interphase microtubule catastrophe promotion. Cyclin B was found to interact with this protein, which targets cell division cycle 2 (CDC2) kinase to microtubules. The phosphorylation of this protein affects microtubule properties and cell cycle progression. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed, the full-length nature of three of which are supported.
uMAP4, the ubiquitous isoform of MAP4, functions in the architecture and positioning of the mitotic spindle in human cells. oMAP4 is predominantly expressed in brain and muscle and has been shown to organise microtubules into antiparallel bundles. mMAP4 is a muscle-specific isoform.
References
Further reading |
https://en.wikipedia.org/wiki/CD99 | CD99 antigen (Cluster of differentiation 99), also known as MIC2 or single-chain type-1 glycoprotein, is a heavily O-glycosylated transmembrane protein that is encoded by the CD99 gene in humans. The protein has a mass of 32 kD. Unusually for a gene present on the X chromosome, the CD99 gene does not undergo X inactivation, and it was the first such pseudoautosomal gene to be discovered in humans.
Expression
It is expressed on all leukocytes but highest on thymocytes and is believed to augment T-cell adhesion and apoptosis of double positive T cells. It has been found in endothelial cells and in the periodontium, including gingival fibroblasts and gingival epithelial cells. It also participates in migration and activation. There is also experimental evidence that it binds to cyclophilin A.
It is found on the cell surface of Ewing's sarcoma tumors and is positive in granulosa cell tumors. It is more expressed in malignant gliomas than in the brain, and such overexpression results in higher levels of invasiveness and lower rates of survival. Antibodies to CD99 are used in diagnostic immunohistochemistry to distinguish Ewing's sarcoma from other tumours of similar histological appearance, as well as for the identification of thymic tumours, and of spindle cell tumours, such as synovial sarcoma, haemangiopericytoma, and meningioma. EWS/FLI is thought to regulate CD99, but knockdown of EWS/FLI results in only a modest reduction in CD99. When CD99 expression is knocked down in |
https://en.wikipedia.org/wiki/P2RX1 | P2X purinoceptor 1, also ATP receptor, is a protein that in humans is encoded by the P2RX1 gene.
The product of this gene belongs to the family of purinoceptors for ATP. This receptor functions as a ligand-gated ion channel with relatively high calcium permeability. Expressed in smooth muscle and platelets. Binding to ATP mediates synaptic transmission between neurons and from neurons to smooth muscle, being responsible, for example, for sympathetic vasoconstriction in small arteries, arterioles and vas deferens. Mouse studies suggest that this receptor is essential for normal male reproductive function. It is possible that the development of selective antagonists for this receptor may provide an effective non-hormonal male contraceptive pill.
See also
P2X receptor
References
Further reading
External links
Ion channels |
https://en.wikipedia.org/wiki/PCBP1 | Poly(rC)-binding protein 1 is a protein that in humans is encoded by the PCBP1 gene.
This intronless gene is thought to have been generated by retrotransposition of a fully processed PCBP-2 mRNA. This gene and PCBP-2 have paralogues (PCBP3 and PCBP4) which are thought to have arisen as a result of duplication events of entire genes. The protein encoded by this gene appears to be multifunctional. It along with PCBP2 and HNRNPK corresponds to the major cellular poly(rC)-binding protein. It contains three K-homologous (KH) domains which may be involved in RNA binding. This encoded protein together with PCBP-2 also functions as translational coactivators of poliovirus RNA via a sequence-specific interaction with stem-loop IV of the IRES and promote poliovirus RNA replication by binding to its 5'-terminal cloverleaf structure.
It has also been implicated in translational control of the 15-lipoxygenase mRNA, human Papillomavirus type 16 L2 mRNA, and hepatitis A virus RNA. The encoded protein is also suggested to play a part in formation of a sequence-specific alpha-globin mRNP complex which is associated with alpha-globin mRNA stability.
References
Further reading |
https://en.wikipedia.org/wiki/PCBP2 | Poly(rC)-binding protein 2 is a protein that in humans is encoded by the PCBP2 gene.
Function
The protein encoded by this gene appears to be multifunctional. It along with PCBP-1 and hnRNPK corresponds to the major cellular poly(rC)-binding proteins. It contains three K-homologous (KH) domains which may be involved in RNA binding. This encoded protein together with PCBP-1 also functions as translational coactivators of poliovirus RNA via a sequence-specific interaction with stem-loop IV of the IRES and promote poliovirus RNA replication by binding to its 5'-terminal cloverleaf structure.
It has also been implicated in translational control of the 15-lipoxygenase mRNA, human Papillomavirus type 16 L2 mRNA, and hepatitis A virus RNA. The encoded protein is also suggested to play a part in formation of a sequence-specific alpha-globin mRNP complex which is associated with alpha-globin mRNA stability.
This multiexon structural mRNA is thought to be retrotransposed to generate PCBP-1 intronless gene which has similar functions. This gene and PCBP-1 has paralogues PCBP3 and PCBP4 which is thought to arose as a result of duplication events of entire genes. It also has two processed pseudogenes PCBP2P1 and PCBP2P2. There are presently two alternatively spliced transcript variants described for this gene.
In humans, the PCBP2 gene overlaps with TUC338, a transcribed ultra-conserved element implicated in Hepatocellular carcinoma.
Interactions
PCBP2 has been shown to interact w |
https://en.wikipedia.org/wiki/PSMB2 | Proteasome subunit beta type-2 also known as 20S proteasome subunit beta-4 (based on systematic nomenclature) is a protein that in humans is encoded by the PSMB2 gene. This protein is one of the 17 essential subunits (alpha subunits 1–7, constitutive beta subunits 1–7, and inducible subunits including beta1i, beta2i, beta5i) that contributes to the complete assembly of 20S proteasome complex. In particular, proteasome subunit beta type-2, along with other beta subunits, assemble into two heptameric rings and subsequently a proteolytic chamber for substrate degradation. The eukaryotic proteasome recognized degradable proteins, including damaged proteins for protein quality control purpose or key regulatory protein components for dynamic biological processes. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides.
Structure
Gene
The gene PSMB2 encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. The gene has 7 exons and locates at chromosome band 1p34.2.
Protein
The human protein proteasome subunit beta type-2 is 23 kDa in size and composed of 201 amino acids. The calculated theoretical pI of this protein is 6.52.
Complex assembly
The proteasome is a multicatalytic proteinase complex with a highly ordered 20S core structure. This barrel-shaped core structure is composed of 4 axially stacked rings of 28 non-identical subunits: the two end rings are each |
https://en.wikipedia.org/wiki/PSMD12 | 26S proteasome non-ATPase regulatory subunit 12 is an enzyme that in humans is encoded by the PSMD12 gene.
Function
The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a non-ATPase subunit of the 19S regulator. A pseudogene has been identified on chromosome 3.
Clinical significance
The proteasome and its subunits are of clinical significance for at least two reasons: (1) a compromised complex assembly or a dysfunctional proteasome can be associated with the underlying pathophysiology of specific diseases, and (2) they can be exploited as drug targets for therapeutic interventions. More recently, more effort has been made to consider the proteasome for the development of novel diagnostic markers and strategies. An improved and comprehensive understanding of the pathophysiology of the |
https://en.wikipedia.org/wiki/UPF1 | Regulator of nonsense transcripts 1 is a protein that in humans is encoded by the UPF1 gene.
Function
This gene encodes a protein that is part of a post-splicing multiprotein complex, the exon junction complex, involved in both mRNA nuclear export and mRNA surveillance. mRNA surveillance detects exported mRNAs with truncated open reading frames and initiates nonsense-mediated mRNA decay (NMD). When translation ends upstream from the last exon-exon junction, this triggers NMD to degrade mRNAs containing premature stop codons. This protein is located in both the cytoplasm and nucleus of the cell. When translation ends, it interacts with the protein that is a functional homolog of yeast Upf2p to trigger mRNA decapping. Use of multiple polyadenylation sites has been noted for this gene.
Interactions
UPF1 has been shown to interact with:
DCP1A,
DCP2,
SMG1,
UPF2,
UPF3A, and
UPF3B.
References
Further reading |
https://en.wikipedia.org/wiki/Adiponectin%20receptor%201 | Adiponectin receptor 1 (AdipoR1) is a protein which in humans is encoded by the ADIPOR1 gene. It is a member of the progestin and adipoQ receptor (PAQR) family, and is also known as PAQR1.
Structure
Similar to G protein-coupled receptors (GPCRs), AdipoR1 also possesses 7 transmembrane domains. However, AdipoR1 is orientated oppositely to GPCRs in the membrane (i.e., cytoplasmic N-terminus, extracellular C-terminus) and does not associate with G proteins.
Function
The adiponectin receptors, AdipoR1 and AdipoR2, serve as receptors for globular and full-length adiponectin and mediate increased AMPK and PPAR-α ligand activities, as well as fatty acid oxidation and glucose uptake by adiponectin. In 2016, the University of Tokyo announced that it would launch an investigation into claims of fabrication of AdipoR1 and AdipoR2 identification data, as accused by an anonymous person/group called Ordinary_researchers.
Ligands
Agonists
Peptide
Adiponectin
ADP-355
ADP-399
Non-peptide
AdipoRon
(–)-Arctigenin
Arctiin
Gramine
Matairesinol
Antagonists
Peptide
ADP-400
See also
Adiponectin receptor
Adiponectin receptor 2
References
External links
Further reading
7TM receptors |
https://en.wikipedia.org/wiki/CAMK4 | Calcium/calmodulin-dependent protein kinase type IV is an enzyme that in humans is encoded by the CAMK4 gene.
The product of this gene belongs to the serine/threonine protein kinase cluster, and to the Ca2+/calmodulin-dependent protein kinase (CAMK) group. This enzyme is a multifunctional serine/threonine protein kinase with limited tissue distribution, that has been implicated in transcriptional regulation in lymphocytes, neurons, and male germ cells.
References
Further reading
External links
EC 2.7.11 |
https://en.wikipedia.org/wiki/SUMO2 | Small ubiquitin-related modifier 2 is a protein that in humans is encoded by the SUMO2 gene.
Function
This gene encodes a protein that is a member of the SUMO (small ubiquitin-like modifier) protein family. It is a ubiquitin-like protein and functions in a manner similar to ubiquitin in that it is bound to target proteins as part of a post-translational modification system. However, unlike ubiquitin, which is primarily associated with targeting proteins for proteasomal degradation, SUMO2 is involved in a variety of cellular processes, such as nuclear transport, transcriptional regulation, apoptosis, and protein stability. It is not active until the last two amino acids of the carboxy-terminus have been cleaved off. Numerous pseudogenes have been reported for this gene. Alternate transcriptional splice variants encoding different isoforms have been characterized.
Interactions
SUMO2 has been shown to interact with TRIM63 and CFAP298.
Clinical significance
Deep hypothermia protects the brain from ischemic injury, which is why it's employed for major cardiovascular procedures that necessitate cardiopulmonary bypass and a period of circulatory arrest. With an experiment conducted to moderate hypothermia, small ubiquitin-like modifier (SUMO1-3) conjugation was significantly activated in the brain. The effects of hypothermia on SUMO conjugation were evaluated in this experiment using Western blot and immunohistochemistry in animals that were either normothermic (37 °C) or |
https://en.wikipedia.org/wiki/STX4 | Syntaxin-4 is a protein that in humans is encoded by the STX4 gene.
Interactions
STX4 has been shown to interact with:
Gelsolin,
NAPA,
RAB4A,
SNAP-25,
SNAP23,
STXBP1,
STXBP5,
Syntaxin binding protein 3,
TXLNB,
VAMP2,
VAMP3, and
Vesicle-associated membrane protein 8.
References
Further reading
External links |
https://en.wikipedia.org/wiki/Thymidine%20kinase%201 | Thymidine kinase 1, soluble (gene name TK1), is a human thymidine kinase.
Two forms of this protein have been identified in animal cells, one in cytosol and one in mitochondria. Activity of the cytosolic enzyme is high in proliferating cells and peaks during the S-phase of the cell cycle; it is very low in resting cells.
Interactions
Thymidine kinase 1 has been shown to interact with P21.
Interactive pathway map
Thymidine Kinase 1 in Cancer
Elevations in serum TK-1 have been found to correlate with the return of breast and other forms of cancer TK-1 can be used to detect cancer earlier, determine what stage it is in, and detect recurrence. Thymidine Kinase 1 can be measured based on its enzyme activity or using immunoassay.
References
Further reading |
https://en.wikipedia.org/wiki/Sodium-hydrogen%20exchange%20regulatory%20cofactor%202 | Sodium-hydrogen exchange regulatory cofactor NHE-RF2 (NHERF-2) also known as tyrosine kinase activator protein 1 (TKA-1) or SRY-interacting protein 1 (SIP-1) is a protein that in humans is encoded by the SLC9A3R2 (solute carrier family 9 isoform A3 regulatory factor 2) gene.
NHERF-2 is a scaffold protein that connects plasma membrane proteins with members of the ezrin/moesin/radixin family and thereby helps to link them to the actin cytoskeleton and to regulate their surface expression. It is necessary for cAMP-mediated phosphorylation and inhibition of SLC9A3. In addition, it may also act as scaffold protein in the nucleus.
Function
This regulatory protein (factor) interacts with a sodium/hydrogen exchanger NHE3 (SLC9A3) in the brush border membrane of the proximal tubule, small intestine, and colon that plays a major role in transepithelial sodium absorption. SLC9A3R2, as well as SLC9A3R1 and protein kinase A phosphorylation, may play a role in NHE3 regulation.
Interactions
Sodium-hydrogen exchange regulatory cofactor 2 has been shown to interact with SGK, Actinin alpha 4, Parathyroid hormone receptor 1, Phosphoinositide-dependent kinase-1, EZR, PODXL, Cystic fibrosis transmembrane conductance regulator and PLCB3.
See also
Solute carrier family
References
Further reading
External links
Solute carrier family
Membrane proteins |
https://en.wikipedia.org/wiki/Cytochrome%20b5%2C%20type%20A | Cytochrome b5, form A (gene name CYB5A), is a human microsomal cytochrome b5.
Cytochrome b5 is a membrane bound hemoprotein which functions as an electron carrier for several membrane bound oxygenases. It has two isoforms produced by alternative splicing. Isoform 1 is bound to the cytoplasmic side of the endoplasmic reticulum. It has a C-terminal transmembrane alpha-helix. Isoform 2 was found in cytoplasm. Defects in CYB5A are the cause of type IV hereditary methemoglobinemia.
References
Further reading
Transmembrane proteins |
https://en.wikipedia.org/wiki/Ventral%20trigeminal%20tract | The ventral trigeminal tract, ventral trigeminothalamic tract, anterior trigeminal tract, or anterior trigeminothalamic tract, is a tract composed of second order neuronal axons. These fibers carry sensory information about discriminative and crude touch, conscious proprioception, pain, and temperature from the head, face, and oral cavity. The ventral trigeminal tract connects the two major components of the brainstem trigeminal complex – the principal, or main sensory nucleus and the spinal trigeminal nucleus, to the ventral posteromedial nucleus of the thalamus.
The ventral trigeminal tract is also called the anterior trigeminal lemniscus.
Structure
The first order neurons (from the trigeminal ganglion) enter the pons and synapse in the principal (chief sensory) nucleus or spinal trigeminal nucleus. Axons of the second order neurons cross the midline and terminate in the ventral posteromedial nucleus of the contralateral thalamus (as opposed to the ventral posterolateral nucleus, as in the dorsal column medial lemniscus (DCML) system). The third order neuron in the thalamus then connects to the sensory cortex of the postcentral gyrus.
See also
Dorsal trigeminal tract
References
Sources
Anthoney, T. R. (1993). Neuroanatomy and the neurologic exam: a thesaurus of synonyms, similar-sounding non-synonyms, and terms of variable meaning. CRC Press.
Norton, N. S. (2016). Netter's head and neck anatomy for dentistry. Elsevier Health Sciences.
External links
Trigeminotha |
https://en.wikipedia.org/wiki/E2F3 | Transcription factor E2F3 is a protein that in humans is encoded by the E2F3 gene.
Function
The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a DNA binding domain, a dimerization domain which determines interaction with the differentiation regulated transcription factor proteins (DP), a transactivation domain enriched in acidic amino acids, and a tumor suppressor protein association domain which is embedded within the transactivation domain. This protein and another 2 members, E2F1 and E2F2, have an additional cyclin binding domain. This protein binds specifically to retinoblastoma protein pRB in a cell-cycle dependent manner. Alternative gene splicing is found in the mouse homolog, but has not reported in human yet.
Interactions
E2F3 has been shown to interact with TFE3 and RYBP.
See also
E2F
References
Further reading
External links
Transcription factors |
https://en.wikipedia.org/wiki/EIF4G2 | Eukaryotic translation initiation factor 4 gamma 2 (also called p97, NAT1, and DAP-5) is a protein that in humans is encoded by the EIF4G2 gene.
Function
Translation initiation is mediated by specific recognition of the cap structure by eukaryotic translation initiation factor 4F (eIF4F), which is a cap binding protein complex that consists of three subunits: eIF4A, eIF4E and eIF4G. The protein encoded by the eIF4G2 gene shares similarity with the C-terminal region of eIF4G1 that contains the binding sites for eIF4A and eIF3. eIF4G2 additionally contains a binding site for eIF4E at the N-terminus. Unlike eIF4G1, which supports cap-dependent and independent translation, the eIF4G2 gene product functions as a general repressor of translation by forming translationally inactive complexes. In vitro and in vivo studies indicate that translation of this mRNA initiates exclusively at a non-AUG (GUG) codon. Alternatively spliced transcript variants encoding different isoforms of this gene have been described.
Interactions
EIF4G2 has been shown to interact with EIF3A.
References
Further reading |
https://en.wikipedia.org/wiki/Equilibrative%20nucleoside%20transporter%201 | Equilibrative nucleoside transporter 1 (ENT1) is a protein that in humans is encoded by the SLC29A1 gene. Multiple alternatively spliced variants, encoding the same protein, have been found for this gene. Expressed on red blood cell surfaces, these variants make up the Augustine blood group system.
Function
This gene is a member of the equilibrative nucleoside transporter family. The gene encodes a transmembrane glycoprotein that localizes to the plasma and mitochondrial membranes and mediates the cellular uptake of nucleosides from the surrounding medium. The protein is categorized as an equilibrative (as opposed to concentrative) transporter that is sensitive to inhibition by nitrobenzylmercaptopurine ribonucleoside (NBMPR). Nucleoside transporters are required for nucleotide synthesis in cells that lack de novo nucleoside synthesis pathways, and are also necessary for the uptake of cytotoxic nucleosides used for cancer and viral chemotherapies.
Genomics
The gene encoding this protein is located on the short arm of chromosome 6 at 6p21.2-p21.1 on the Watson (plus) strand. It is 14,647 bases in length. The encoded protein has 456 amino acid residues with 11 predicted transmembrane domains. The predicted molecular weight is 50.219 kiloDaltons. The protein is post translationally glycosylated and expressed in all tissue with the apparent exception of skeletal muscle. The highest levels are found in the liver, heart, testis, spleen, lung, kidney and brain.
Interactive pa |
https://en.wikipedia.org/wiki/GJA5 | Gap junction alpha-5 protein (GJA5), also known as connexin 40 (Cx40) — is a protein that in humans is encoded by the GJA5 gene.
Function
This gene is a member of the connexin gene family. The encoded protein is a component of gap junctions, which are composed of arrays of intercellular channels that provide a route for the diffusion of low molecular weight materials from cell to cell. Mutations in this gene may be associated with atrial fibrillation. Alternatively spliced transcript variants encoding the same isoform have been described.
GJA5 has been identified as the gene that is responsible for the phenotypes observed with congenital heart diseases on the 1q21.1 location. In case of a duplication of GJA5 tetralogy of Fallot is more common. In case of a deletion other congenital heart diseases than tetralogy of Fallot are more common.
Related gene problems
1q21.1 deletion syndrome
1q21.1 duplication syndrome
See also
Connexin
Gap junction
References
Further reading
Connexins |
https://en.wikipedia.org/wiki/PRPF8 | Pre-mRNA-processing-splicing factor 8 is a protein that in humans is encoded by the PRPF8 gene.
Function
Pre-mRNA splicing occurs in 2 sequential transesterification steps. The protein encoded by this gene is a component of both U2- and U12-dependent spliceosomes, and found to be essential for the catalytic step II in pre-mRNA splicing process. It contains several WD repeats, which function in protein-protein interactions. This protein has a sequence similarity to yeast Prp8 protein. This gene is a candidate gene for autosomal dominant retinitis pigmentosa.
Interactions
PRPF8 has been shown to interact with WDR57 and EFTUD2.
References
Further reading
External links
GeneReviews/NIH/NCBI/UW entry on Retinitis Pigmentosa Overview
Spliceosome |
https://en.wikipedia.org/wiki/RUVBL2 | RuvB-like 2 (E. coli), also known as RUVBL2, is a human gene coding for a protein belonging to the AAA+ family of proteins.
Function
This gene encodes the second human homologue of the bacterial RuvB gene. Bacterial RuvB protein is a DNA helicase essential for homologous recombination and DNA double-strand break repair. However, the evidence for whether RUVBL2 has DNA helicase activity is contradictory. This gene is physically linked to the CGB/LHB gene cluster on chromosome 19q13.3, and is very close (55 nt) to the LHB gene, in the opposite orientation.
Interactions
RUVBL2 has been shown to interact with RuvB-like 1 and Activating transcription factor 2.
References
Further reading |
https://en.wikipedia.org/wiki/COPS6 | COP9 signalosome complex subunit 6 is a protein that in humans is encoded by the COPS6 gene.
Function
The protein encoded by this gene is one of the eight subunits of COP9 signalosome, a highly conserved protein complex that functions as an important regulator in multiple signaling pathways. The structure and function of COP9 signalosome is similar to that of the 19S regulatory particle of 26S proteasome. COP9 signalosome has been shown to interact with SCF-type E3 ubiquitin ligases and act as a positive regulator of E3 ubiquitin ligases. This protein belongs to translation initiation factor 3 (eIF3) superfamily. It is involved in the regulation of cell cycle and likely to be a cellular cofactor for HIV-1 accessory gene product Vpr.
Interactions
COPS6 has been shown to interact with EIF3S6.
References
Further reading
External links |
https://en.wikipedia.org/wiki/APLP2 | Amyloid-like protein 2, also known as APLP2, is a protein that in humans is encoded by the APLP2 gene. APLP2 along with APLP1 are important modulators of glucose and insulin homeostasis.
Gene location
The human APLP2 gene is located on the long (q) arm of chromosome 11 at region 2 band 4, from base pair 130, 069, 821 to base pair 130, 144, 811 (GRCh38.p7).
Protein structure
APLP2 consists of 763 amino acids, with 31 amino acids making up the signal peptide and 732 amino acids making up the chain of the protein.
Extracellular domain
The extracellular domain (residues 32-692) contains the E1 domain, E2 domain, and BPTI/Kunitz inhibitor domain. The E1 domain contains two independent folding units, the growth factor-like domain (GFLD) and the copper-binding domain (CuBD). GFLD has a highly charged basic surface and a highly flexible region consisting of an N-terminal loop formed by a disulphide bridge. CuBD consists of an alpha-helix that is tightly packed on a triple-stranded beta-sheet.
The E2 domain is the largest subdomain of APLP2 and consists of six alpha-helixes. The N-terminal double stranded coiled coil structure of the first monomer of E2 packs against the C-terminal triple stranded coiled coil structure of the second monomer.
The BPTI/Kunitz inhibitor domain (residues 306-364) is ‘Cys-rich’ and is capable of inhibiting several proteases.
The ectodomain of APLP2 is dimeric and contains multiple binding sites for metal ions and components of the extracellular |
https://en.wikipedia.org/wiki/HOXB7 | Homeobox protein Hox-B7 is a protein that in humans is encoded by the HOXB7 gene.
Function
This gene is a member of the Antp homeobox family and encodes a protein with a homeobox DNA-binding domain. It is included in a cluster of homeobox B genes located on chromosome 17. The encoded nuclear protein functions as a sequence-specific transcription factor that is involved in cell proliferation and differentiation. Increased expression of this gene is associated with some cases of melanoma and ovarian carcinoma.
Interactions
HOXB7 has been shown to interact with PBX1 and CREB-binding protein.
See also
Homeobox
References
Further reading
External links
Transcription factors |
https://en.wikipedia.org/wiki/Non-POU%20domain-containing%20octamer-binding%20protein | Non-POU domain-containing octamer-binding protein (NonO) is a protein that in humans is encoded by the NONO gene.
The NonO protein belongs to the Drosophila behaviour/human splicing (DBHS) family of proteins. Proteins in the DHBS family include mammalian SFPQ (splicing factor, proline- and glutamine-rich; a.k.a. PSF), NONO (Non-POU domain-containing octamer-binding protein; a.k.a. p54nrb) and PSPC1 (paraspeckle component 1; a.k.a. PSP1) and invertebrate NONA (Protein no-on-transient A) and Hrp65.
Interactions
NONO has been shown to interact with SFPQ, SPI1 and Androgen receptor.
Functions
NONO is involved with many nuclear processes and binds to both DNA and RNA.
As with all proteins of the DBHS familprotein is described as a multifunctional nuclear protein. The NONO protein has been shown to be implicated in many biological functions including, pre-mRNA splicing; activation of transcription; termination of transcription; DNA unwinding and pairing and maintaining correct circadian clock function.
NONO has been identified to bind with Rasd1 protein, resulting dimer Rasd1 may act to modulate the function of NONO to down regulate the expression of the CREB genes, NR4A1 and Nr4A2.
NONO binds to SFPQ to form a heterodimer that interacts with the MATR3 protein. The interaction of these three proteins may be part of the process in the nucleus that is responsible for the retention of RNAs that are defective, not yet mature enough to be exported or are designed to be retaine |
https://en.wikipedia.org/wiki/P2RY2 | P2Y purinoceptor 2 is a protein that in humans is encoded by the P2RY2 gene.
The product of this gene, P2Y2 belongs to the family of G-protein coupled receptors. This family has several receptor subtypes with different pharmacological selectivity, which overlaps in some cases, for various adenosine and uridine nucleotides. This receptor is responsive to both adenosine and uridine nucleotides. It may participate in control of the cell cycle of endometrial carcinoma cells. Three transcript variants encoding the same protein have been identified for this gene.
See also
P2Y receptor
Denufosol, a P2Y2 agonist
References
Further reading
External links
G protein-coupled receptors |
https://en.wikipedia.org/wiki/PPP1CC | Serine/threonine-protein phosphatase PP1-gamma catalytic subunit is an enzyme that in humans is encoded by the PPP1CC gene.
Interactions
PPP1CC has been shown to interact with PPP1R15A, SMARCB1, TLX1 and PPP1R9B.
References
Further reading |
https://en.wikipedia.org/wiki/PPP5C | Serine/threonine-protein phosphatase 5 is an enzyme that in humans is encoded by the PPP5C gene.
Model organisms
Model organisms have been used in the study of PPP5C function. A conditional knockout mouse line, called Ppp5ctm1a(EUCOMM)Wtsi was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.
Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Twenty five tests were carried out on mutant mice and five significant abnormalities were observed. Homozygous mutant males had decreased body weight, body length and respiratory quotient. Both sexes had increased T cell numbers and a range of skeletal abnormalities identified by radiography.
Interactions
PPP5C has been shown to interact with ASK1, CRY2 GNA12. and Rac1,
References
Further reading
Genes mutated in mice |
https://en.wikipedia.org/wiki/PSMB3 | Proteasome subunit beta type-3, also known as 20S proteasome subunit beta-3, is a protein that in humans is encoded by the PSMB3 gene. This protein is one of the 17 essential subunits that contribute to the complete assembly of the 20S proteasome complex. In particular, proteasome subunit beta type-2, along with other beta subunits, assemble into two heptameric rings and subsequently a proteolytic chamber for substrate degradation. The eukaryotic proteasome recognizes degradable proteins, including damaged proteins for protein quality control purpose or key regulatory protein components for dynamic biological processes.
Structure
Protein expression
The gene PSMB3 encodes a member of the proteasome B-type family, also known as the T1B family, that is a 20S core beta subunit. Pseudogenes have been identified on chromosomes 2 and 12. The gene has 6 exons and locates at chromosome band 17q12. The human protein proteasome subunit beta type-3 is 23 kDa in size and composed of 205 amino acids. The calculated theoretical pI of this protein is 6.14.
Complex assembly
The proteasome is a multicatalytic proteinase complex with a highly ordered 20S core structure. This barrel-shaped core structure is composed of 4 axially stacked rings of 28 non-identical subunits: the two end rings are each formed by 7 alpha subunits, and the two central rings are each formed by 7 beta subunits. Three beta subunits (beta1, beta2, and beta5) each contain a proteolytic active site and have distinct su |
https://en.wikipedia.org/wiki/PSMD5 | 26S proteasome non-ATPase regulatory subunit 5 is an enzyme that in humans is encoded by the PSMD5 gene.
Function
The 26S proteasome is a multicatalytic proteinase complex with a highly ordered structure composed of 2 complexes, a 20S core and a 19S regulator. The 20S core is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. The 19S regulator is composed of a base, which contains 6 ATPase subunits and 2 non-ATPase subunits, and a lid, which contains up to 10 non-ATPase subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a non-ATPase subunit of the 19S regulator base.
Clinical significance
The proteasome and its subunits are of clinical significance for at least two reasons: (1) a compromised complex assembly or a dysfunctional proteasome can be associated with the underlying pathophysiology of specific diseases, and (2) they can be exploited as drug targets for therapeutic interventions. More recently, more effort has been made to consider the proteasome for the development of novel diagnostic markers and strategies. An improved and comprehensive understanding of the pathophysiology of the proteasome should lead to clinical applicatio |
https://en.wikipedia.org/wiki/NOX4 | NADPH oxidase 4 is an enzyme that in humans is encoded by the NOX4 gene, and is a member of the NOX family of NADPH oxidases.
Function
Oxygen sensing is essential for homeostasis in all aerobic organisms. A phagocyte-type oxidase, similar to that responsible for the production of large amounts of reactive oxygen species (ROS) in neutrophil granulocytes, with resultant antimicrobial activity, has been postulated to function in the kidney as an oxygen sensor that regulates the synthesis of erythropoietin in the renal cortex.
Nox4 protects the vasculature against inflammatory stress. Nox-dependent reactive oxygen species modulation by amino endoperoxides can induce apoptosis in high Nox4-expressing cancer cells.
A study found that NOX4 facilitates certain beneficial adaptive responses to exercise mediated by ROS. Moreover, reductions in skeletal muscle NOX4 in aging and obesity was shown to contribute to the development of insulin resistance and may promote oxidative stress.
References
Further reading |
https://en.wikipedia.org/wiki/PIAS4 | E3 SUMO-protein ligase PIAS4 is one of several protein inhibitor of activated STAT (PIAS) proteins. It is also known as protein inhibitor of activated STAT protein gamma (PIASg or PIASy), and is an enzyme that in humans is encoded by the PIAS4 gene.
Interactions
PIAS4 has been shown to interact with Mothers against decapentaplegic homolog 6, Mothers against decapentaplegic homolog 7 and Lymphoid enhancer-binding factor 1.
References
Further reading |
https://en.wikipedia.org/wiki/BNIP3 | BCL2/adenovirus E1B 19 kDa protein-interacting protein 3 is a protein found in humans that is encoded by the BNIP3 gene.
BNIP3 is a member of the apoptotic Bcl-2 protein family. It can induce cell death while also assisting with cell survival. Like many of the Bcl-2 family proteins, BNIP3 modulates the permeability state of the outer mitochondrial membrane by forming homo- and hetero-oligomers inside the membrane. Upregulation results in a decrease in mitochondrial potential, an increase in reactive oxygen species, mitochondrial swelling and fission, and an increase in mitochondrial turnover via autophagy. Sequence similarity with Bcl-2 family members was not detected. Humans and other animals (Drosophila, Caenorhabditis), as well as lower eukaryotes (Dictyostelium, Trypanosoma, Cryptosporidium, Paramecium) encode several BNIP3 paralogues including the human NIP3L, which induces apoptosis by interacting with viral and cellular anti-apoptosis proteins.
Structure
The right-handed parallel helix-helix structure of the domain with a hydrogen bond-rich His-Ser node in the middle of the membrane, accessibility of the node for water, and continuous hydrophilic track across the membrane suggest that the domain can provide an ion-conducting pathway through the membrane. Incorporation of the BNIP3 transmembrane domain into an artificial lipid bilayer resulted in a pH-dependent conductivity increase. Necrosis-like cell death induced by BNIP3 may be related to this activity.
Function |
https://en.wikipedia.org/wiki/S100A2 | S100 calcium-binding protein A2 (S100A2) is a protein that in humans is encoded by the S100A2 gene and it is located on chromosome 1q21 with other S100 proteins.
Tissue and subcellular distribution
S100A2, also known as CaN19 or S100L was first isolated from bovine lung tissue. However, in human tissue it was discovered several years later, in the mammary epithelial cells. Under normal circumstances it is highly expressed in human lungs, prostate, kidneys, hair follicles and salivary and mammary glands. S100A2 is predominantly found in the nucleus, which is not very common in other S100 proteins. Moreover, it can also be found in the cytoplasm, and its distribution is rather diffuse. Its occurrence in cytoplasm is most likely dependent on calcium levels in the cell. In the extracellular environment, it can be found as a homodimer in vivo and in vitro, but it also exists in monomeric, polymeric and multimeric forms. In multimeric form, it functions as a RAGE receptor ligand.
Function
S100A2 is important in cytoskeleton organization. Also, S100A2 is induced by p53, which it interacts and participates in the transcription of p21. It also plays a role in differentiation, regeneration of tissues and healing and it was shown it attract eosinophils by chemotaxis.
Clinical significance
Its expression is reduced in many types of cancer, thereby distinguishing the cancerous expression profile of the other proteins of the S100 group. It has been reported that S100A2 is downregu |
https://en.wikipedia.org/wiki/SCP2 | Non-specific lipid-transfer protein also known as sterol carrier protein 2 (SCP-2) or propanoyl-CoA C-acyltransferase is a protein that in humans is encoded by the SCP2 gene.
Function
This gene encodes two proteins: sterol carrier protein X (SCPx) and sterol carrier protein 2 (SCP2), as a result of transcription initiation from 2 independently regulated promoters. The transcript initiated from the proximal promoter encodes the longer SCPx protein, and the transcript initiated from the distal promoter encodes the shorter SCP2 protein, with the 2 proteins sharing a common C-terminus. Evidence suggests that the SCPx protein is a peroxisome-associated thiolase that is involved in the oxidation of branched chain fatty acids, while the SCP2 protein is thought to be an intracellular lipid transfer protein. Alternative splicing of this gene produces multiple transcript variants, some encoding different isoforms. The full-length nature of all transcript variants has not been determined.
Clinical significance
This gene is highly expressed in organs involved in lipid metabolism, and may play a role in Zellweger syndrome, in which cells are deficient in peroxisomes and have impaired bile acid synthesis.
Interactions
SCP2 has been shown to interact with Caveolin 1 and peroxisomal receptor PEX5.
References
Further reading
EC 2.3.1 |
https://en.wikipedia.org/wiki/Peptide%20transporter%201 | Peptide transporter 1 (PepT 1) also known as solute carrier family 15 member 1 (SLC15A1) is a protein that in humans is encoded by SLC15A1 gene. PepT 1 is a solute carrier for oligopeptides. It functions in renal oligopeptide reabsorption and in the intestines in a proton dependent way, hence acting like a cotransporter.
Function
SLC15A1is localized to the brush border membrane of the intestinal epithelium and mediates the uptake of di- and tripeptides from the lumen into the enterocytes. This protein plays an important role in the uptake and digestion of dietary proteins. This protein also facilitates the absorption of numerous peptidomimetic drugs. Peptide transporter 1 functions in nutrient and drug transport have been studied using intestinal organoids.
See also
Solute carrier family
References
Further reading
Membrane proteins
Solute carrier family |
https://en.wikipedia.org/wiki/USH2A | Usherin is a protein that in humans is encoded by the USH2A gene.
This gene encodes the protein Usherin that contains laminin EGF motifs, a pentraxin domain, and many fibronectin type III motifs. The encoded basement membrane-associated protein may be important in development and homeostasis of the inner ear and retina. Mutations within this gene have been associated with Usher syndrome type IIa. Alternatively spliced transcript variants that encode different isoforms have been described.
References
Further reading
External links
GeneReviews/NCBI/NIH/UW entry on Usher Syndrome Type II |
https://en.wikipedia.org/wiki/ADAM12 | Disintegrin and metalloproteinase domain-containing protein 12 (previously Meltrin) is an enzyme that in humans is encoded by the ADAM12 gene. ADAM12 has two splice variants: ADAM12-L, the long form, has a transmembrane region and ADAM12-S, a shorter variant, is soluble and lacks the transmembrane and cytoplasmic domains.
Function
This gene encodes a member of the ADAM (a disintegrin and metalloprotease) protein family. Members of this family are membrane-anchored proteins structurally related to snake venom disintegrins, and have been implicated in a variety of biological processes involving cell-cell and cell-matrix interactions, including fertilization, muscle development, and neurogenesis. This gene has two alternatively spliced transcripts: a shorter secreted form and a longer membrane-bound form. The shorter form is found to stimulate myogenesis.
Clinical Significance
ADAM 12, a metalloprotease that binds insulin growth factor binding protein-3 (IGFBP-3), appears to be an effective early Down syndrome marker. Decreased levels of ADAM 12 may be detected in cases of trisomy 21 as early as 8 to 10 weeks gestation. Maternal serum ADAM 12 and PAPP-A levels at 8 to 9 weeks gestation in combination with maternal age yielded a 91% detection rate for Down syndrome at a 5% false-positive rate. When nuchal translucency data from approximately 12 weeks gestation was added, this increased the detection rate to 97%.
ADAM12 has also been implicated in the development of patholo |
https://en.wikipedia.org/wiki/CUL4A | Cullin-4A is a protein that in humans is encoded by the CUL4A gene. CUL4A belongs to the cullin family of ubiquitin ligase proteins and is highly homologous to the CUL4B protein. CUL4A regulates numerous key processes such as DNA repair, chromatin remodeling, spermatogenesis, haematopoiesis and the mitotic cell cycle. As a result, CUL4A has been implicated in several cancers and the pathogenesis of certain viruses including HIV. A component of a CUL4A complex, Cereblon, was discovered to be a major target of the teratogenic agent thalidomide.
Structure
CUL4A protein is 759 amino acids long and forms an extended, rigid structure primarily consisting of alpha-helices. At the N-terminus, CUL4A binds to the beta-propeller of the DDB1 adaptor protein which interacts with numerous DDB1-CUL4-Associated Factors (DCAFs). As a result, the N-terminus is crucial for the recruitment of substrates for the ubiquitin ligase complex. At the C-terminal end, CUL4A interacts with the RBX1/ROC1 protein via its RING domain. RBX1 is a core component of Cullin-RING ubiquitin ligase (CRL) complexes and functions to recruit E2 ubiquitin conjugating enzymes. Therefore, the C-terminus of CUL4A - along with RBX1 and activated E2 enzymes - compose the catalytic core of CRL4 complexes. CUL4A is also modified by covalent attachment of a NEDD8 molecule at a highly conserved lysine residue in the C-terminal region. This modification appears to induce conformational changes which promotes flexibility in the |
https://en.wikipedia.org/wiki/RuvB-like%201 | RuvB-like 1 (E. coli), also known as RUVBL1 and TIP49, is a human gene. RUVBL1 can form a hexamer. The hexamer can form a dodecamer with RUVBL2 protein.
Possesses single-stranded DNA-stimulated ATPase and ATP-dependent DNA helicase (3' to 5') activity; hexamerization is thought to be critical for ATP hydrolysis and adjacent subunits in the ring-like structure contribute to the ATPase activity.
Interactions
RuvB-like 1 has been shown to interact with:
ACTL6A,
Beta-catenin,
EP400,
Myc, and
RUVBL2.
References
Further reading |
https://en.wikipedia.org/wiki/ADAM15 | Disintegrin and metalloproteinase domain-containing protein 15 is an enzyme that in humans is encoded by the ADAM15 gene.
Function
The protein encoded by this gene is a member of the ADAM (a disintegrin and metalloproteinase) protein family. ADAM family members are type I transmembrane glycoproteins known to be involved in cell adhesion and proteolytic ectodomain processing of cytokines and adhesion molecules. This protein contains multiple functional domains including a zinc-binding metalloprotease domain, a disintegrin-like domain, as well as an EGF-like domain. Through its disintegrin-like domain, this protein specifically interacts with the integrin beta chain, beta 3. It also interacts with Src family protein-tyrosine kinases in a phosphorylation-dependent manner, suggesting that this protein may function in cell-cell adhesion as well as in cellular signaling. Multiple alternatively spliced transcript variants encoding distinct isoforms have been observed.
Clinical significance
Arthritis
ADAM15 has been associated with a number of diseases, most recently Rheumatoid Arthritis where it is required for the activation of the FAK and Src pathways to generate apoptosis resistance in response to apoptotic signalling or cell stress. ADAM15 also has an antiapoptotic effect in osteoarthritic chondrocytes.
Cancer
The precise role of ADAM15 in cancer is still unclear but the metalloprotein has been linked to a number of different cancerous diseases such as Breast cancer wh |
https://en.wikipedia.org/wiki/AP1M1 | AP-1 complex subunit mu-1 is a protein that in humans is encoded by the AP1M1 gene.
Function
The protein encoded by this gene is the medium chain of the trans-Golgi network clathrin-associated protein complex AP-1. The other components of this complex are beta-prime-adaptin, gamma-adaptin, and the small chain AP1S1. This complex is located at the Golgi vesicle and links clathrin to receptors in coated vesicles. These vesicles are involved in endocytosis and Golgi processing.
Interactions
AP1M1 has been shown to interact with VAMP4 and AP1G1.
References
Further reading
External links |
https://en.wikipedia.org/wiki/CD83 | CD83 (Cluster of Differentiation 83) is a human protein encoded by the gene.
Structure
The membrane-bound form of CD83 consists of an extracellular V-type immunoglobulin-like domain, a transmembrane domain and a cytoplasmic signaling tail. A free soluble form consists of the immunoglobulin-like domain alone. Membrane-bound CD83 is expected to form trimers. Soluble CD83 is able to assemble into dodecameric complexes.
Gene
The CD83 gene is located on human chromosome 6p23 and mouse chromosome 13. In humans, a promoter 261 bp upstream consists of five NF-κB and three interferon regulatory factor binding sites, reflecting the involvement of CD83 in inflammation, as well as binding sites for the aryl hydrocarbon receptor. The latter also occur in an enhancer sequence located 185 bp downstream, inside the second intron, and may suggest negative regulation of transcription by microbial metabolites produced in the gut.
Function
The transmembrane domain of membrane-bound CD83 stabilizes MHC II, costimulatory molecules and CD28 in the membrane by antagonizing MARCH-family E3 ubiquitin ligases.
Ligands
It is not clear what ligands interact with CD83, but membrane-bound CD83 may homotypically interact with the soluble form, suggesting autocrine immune regulation. However, it contrasts with differences between the single expression of soluble CD83 on monocytes and membrane-bound CD83 on activated dendritic cells seems also as their good marker. Soluble CD83 also binds to CD154, l |
https://en.wikipedia.org/wiki/Adenosine%20A3%20receptor | {{DISPLAYTITLE:Adenosine A3 receptor}}
The adenosine A3 receptor, also known as ADORA3, is an adenosine receptor, but also denotes the human gene encoding it.
Function
Adenosine A3 receptors are G protein-coupled receptors that couple to Gi/Gq and are involved in a variety of intracellular signaling pathways and physiological functions. It mediates a sustained cardioprotective function during cardiac ischemia, it is involved in the inhibition of neutrophil degranulation in neutrophil-mediated tissue injury, it has been implicated in both neuroprotective and neurodegenerative effects, and it may also mediate both cell proliferation and cell death.
Recent publications demonstrate that adenosine A3 receptor antagonists (SSR161421) could have therapeutic potential in bronchial asthma (17,18).
Gene
Multiple transcript variants encoding different isoforms have been found for this gene.
Therapeutic implications
An adenosine A3 receptor agonist (CF-101) is in clinical trials for the treatment of rheumatoid arthritis.
In a mouse model of infarction the A3 selective agonist CP-532,903 protected against myocardial ischemia and reperfusion injury.
Selective Ligands
A number of selective A3 ligands are available.
Agonists/Positive Allosteric Modulators
2-(1-Hexynyl)-N-methyladenosine
CF-101 (IB-MECA)
CF-102
2-Cl-IB-MECA
CP-532,903
Inosine
LUF-6000
MRS-3558
AST-004
Antagonists/Negative Allosteric Modulators
KF-26777
MRS-545
MRS-1191
MRS-1220
MRS-1334
MRS-1523
MRS |
https://en.wikipedia.org/wiki/CD69 | CD69 (Cluster of Differentiation 69) is a human transmembrane C-Type lectin protein encoded by the gene. It is an early activation marker that is expressed in hematopoietic stem cells, T cells, and many other cell types in the immune system. It is also implicated in T cell differentiation as well as lymphocyte retention in lymphoid organs.
Function
The activation of T lymphocytes and Natural Killer (NK) cells, both in vivo and in vitro, induces expression of CD69. This molecule, which appears to be the earliest inducible cell surface glycoprotein acquired during lymphoid activation, is involved in lymphocyte proliferation and functions as a signal-transmitting receptor in lymphocytes, including natural killer (NK) cells, and platelets (Cambiaggi et al., 1992) [supplied by OMIM].
Structure and ligands
The gene encoding CD69 is located in the NK gene complex on chromosome 6 and chromosome 12 in mice and humans respectively. Activation signaling pathways in lymphocytes, NK cells, dendritic cells and other cell types upregulate transcription factors, such as NF-κB, ERG-1 (erythroblast transformation-specific related gene-1), and AP-1 (activator protein), in order to promote the transcription of the CD69 gene. The CD69 protein is subject to post-translational modifications. Namely, it is differentially glycosylated to produce either a 28 kDa peptide or a 32 kDa peptide. Two of these peptides randomly combine to form a homodimer linked by a disulfide bond. These subunits have |
https://en.wikipedia.org/wiki/RCC1 | Regulator of chromosome condensation 1, also known as RCC1, Ran guanine nucleotide exchange factor and RanGEF, is the name for a human gene and protein.
RCC1 also functions as a guanine nucleotide exchange factor for Ran GTPase.
Interactions
RCC1 has been shown to interact with RANBP3 and Ran (biology).
References
Further reading |
https://en.wikipedia.org/wiki/DDB2 | DNA damage-binding protein 2 is a protein that in humans is encoded by the DDB2 gene.
Structure
As indicated by Rapić-Otrin et al. in 2003, the DDB2 gene is located on human chromosome 11p11.2, spans a region of approximately 24 – 26 kb and includes 10 exons. The DDB2 protein contains five putative WD40 repeats (sequences of about 40 amino acids that can interact with each other) positioned downstream from the second exon. The WD40 motif identified in DDB2 is characteristic of proteins involved in the recognition of chromatin proteins. The C-terminal region of DDB2 (a 48 kDa molecular weight protein) is essential for binding to DDB1 (a larger 127 kDa protein). Together, the two proteins form a UV-damaged DNA binding protein complex (UV-DDB).
Deficiency in humans
If humans have a mutation in each copy of their DDB2 gene, this causes a mild form of the human disease xeroderma pigmentosum, called XPE. Patients in the XPE group have mild dermatological manifestations and are neurologically unaffected. Mutation in the DDB2 gene causes a deficiency in nucleotide excision repair of DNA. This deficiency is also mild, showing 40 to 60% of normal repair capability and a modest sensitivity to UV light in comparison to the sensitivities of cells defective in the other XP genes XPA, XPB, XPC, XPD, XPF and XPG.
Function
Binding to damaged DNA
As shown by Wittschieben et al., when DDB2 is in a complex with DDB1, forming the heterodimer DDB, this complex binds strongly to DNA co |
https://en.wikipedia.org/wiki/DLG3 | Disks large homolog 3 (DLG3) also known as neuroendocrine-DLG or synapse-associated protein 102 (SAP-102) is a protein that in humans is encoded by the DLG3 gene. DLG3 is a member of the membrane-associated guanylate kinase (MAGUK) superfamily of proteins.
Interactions
DLG3 has been shown to interact with:
APC,
CRIPT,
DLG4,
EXOC3,
EXOC4,
GRIN2A,
GRIN2B,
GRIN2C,
KCNJ12
PTK2B, and
SYNGAP1.
Model organisms
Model organisms have been used in the study of DLG3 function. A conditional knockout mouse line called Dlg3tm1a(EUCOMM)Wtsi was generated at the Wellcome Trust Sanger Institute. Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion. Additional screens performed: - In-depth immunological phenotyping
References
Further reading |
https://en.wikipedia.org/wiki/DNA%20%28cytosine-5%29-methyltransferase%203A | DNA (cytosine-5)-methyltransferase 3A is an enzyme that catalyzes the transfer of methyl groups to specific CpG structures in DNA, a process called DNA methylation. The enzyme is encoded in humans by the DNMT3A gene.
This enzyme is responsible for de novo DNA methylation. Such function is to be distinguished from maintenance DNA methylation which ensures the fidelity of replication of inherited epigenetic patterns. DNMT3A forms part of the family of DNA methyltransferase enzymes, which consists of the protagonists DNMT1, DNMT3A and DNMT3B.
While de novo DNA methylation modifies the information passed on by the parent to the progeny, it enables key epigenetic modifications essential for processes such as cellular differentiation and embryonic development, transcriptional regulation, heterochromatin formation, X-inactivation, imprinting and genome stability.
DNMT3a is the gene most commonly found mutated in clonal hematopoiesis, a common aging-related phenomenon in which hematopoietic stem cells (HSCs) or other early blood cell progenitors contribute to the formation of a genetically distinct subpopulation of blood cells.
Gene
DNMT3A is a 130 kDa protein encoded by 23 exons found on chromosome 2p23 in humans. There exists a 98% homology between human and murine homologues. DNMT3A is widely expressed among mammals.
There are two main protein isoforms, DNMT3A1 and DNMT3A2 with molecular weights of about 130 kDa and 100 kDa, respectively. The DNMT3A2 protein, which lacks |
https://en.wikipedia.org/wiki/E2F2 | Transcription factor E2F2 is a protein that in humans is encoded by the E2F2 gene.
Function
The protein encoded by this gene is a member of the E2F family of transcription factors. The E2F family plays a crucial role in the control of cell cycle and action of tumor suppressor proteins and is also a target of the transforming proteins of small DNA tumor viruses. The E2F proteins contain several evolutionally conserved domains found in most members of the family. These domains include a DNA binding domain, a dimerization domain which determines interaction with the differentiation regulated transcription factor proteins (DP), a transactivation domain enriched in acidic amino acids, and a tumor suppressor protein association domain which is embedded within the transactivation domain. This protein and another 2 members, E2F1 and E2F3, have an additional cyclin binding domain. This protein binds specifically to retinoblastoma protein pRB in a cell-cycle dependent manner, and it exhibits overall 46% amino acid identity to E2F1.
Interactions
E2F2 has been shown to interact with:
BRD2,
RYBP, and
RB1.
See also
E2F
References
Further reading
External links
Transcription factors |
https://en.wikipedia.org/wiki/AKT3 | RAC-gamma serine/threonine-protein kinase is an enzyme that in humans is encoded by the AKT3 gene.
Function
The protein encoded by this gene is a member of the AKT subfamily of serine/threonine protein kinases. AKT kinases are known to be regulators of cell signaling in response to insulin and growth factors. They are involved in a wide variety of biological processes including cell proliferation, differentiation, apoptosis, tumorigenesis, as well as glycogen synthesis and glucose uptake. This kinase has been shown to be stimulated by platelet-derived growth factor (PDGF), insulin, and insulin-like growth factor 1 (IGF1). Alternatively splice transcript variants encoding distinct isoforms have been described. Mice lacking Akt3 have a normal glucose metabolism (no diabetes), have approximately normal body weight, but have a 25% reduction in brain mass. Incidentally, Akt3 is highly expressed in the brain.
Interactions
AKT3 has been shown to interact with Protein kinase Mζ.
References
Further reading
External links
EC 2.7.11
Protein kinases |
https://en.wikipedia.org/wiki/ABI1 | Abl interactor 1 also known as Abelson interactor 1 (Abi-1) is a protein that in humans is encoded by the ABI1 gene.
Function
Abl interactor 1 has been found to form a complex with EPS8 and SOS1, and is thought to be involved in the transduction of signals from Ras to Rac. In addition, the encoded protein may play a role in the regulation of EGF-induced Erk pathway activation as well as cytoskeletal reorganization and EGFR signaling. Several transcript variants encoding multiple isoforms have been found for this gene.
Abi1 is adaptor protein. It interacts with c-Abl and WAVE2 which is an actin polymerization regulator. It is known that Abi1 enhances the phosphorylation of WAVE2 by c-Abl. The phosphorylation of c-Abl promotes actin polymerization. Furthermore, Abi1 is a component of the WAVE complex. Some research has shown that knockdown of Abi1 by siRNA promoted degradation of WAVE complex proteins.
Interactions
ABI1 has been shown to interact with
ENAH, NCKAP1, EPS8, and SOS1.
References
Further reading
External links |
https://en.wikipedia.org/wiki/RAPGEF3 | Rap guanine nucleotide exchange factor 3 also known as exchange factor directly activated by cAMP 1 (EPAC1) or cAMP-regulated guanine nucleotide exchange factor I (cAMP-GEFI) is a protein that in humans is encoded by the RAPGEF3 gene.
As the name suggests, EPAC proteins (EPAC1 and EPAC2) are a family of intracellular sensors for cAMP, and function as nucleotide exchange factors for the Rap subfamily of RAS-like small GTPases.
History and discovery
Since the landmark discovery of the prototypic second messenger cAMP in 1957, three families of eukaryotic cAMP receptors have been identified to mediate the intracellular functions of cAMP. While protein kinase A (PKA) or cAMP-dependent protein kinase and cyclic nucleotide regulated ion channel (CNG and HCN) were initially unveiled in 1968 and 1985 respectively; EPAC genes were discovered in 1998 independently by two research groups. Kawasaki et al. identified cAMP-GEFI and cAMP-GEFII as novel genes enriched in brain using a differential display protocol and by screening clones with cAMP-binding motif. De Rooij and colleagues performed a database search for proteins with sequence homology to both GEFs for Ras and Rap1 and to cAMP-binding sites, which led to the identification and subsequent cloning of RAPGEF3 gene. The discovery of EPAC family cAMP sensors suggests that the complexity and possible readouts of cAMP signaling are much more elaborate than previously envisioned. This is due to the fact that the net physiological eff |
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