| GBP2 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | GBP2 , guanylate binding protein 2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 600412 MGI: 102772 HomoloGene: 10289 GeneCards: GBP2 | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Interferon-induced guanylate-binding protein 2 is a protein that in humans is encoded by the GBP2 gene. [5] [6] GBP2 is a gene related to the superfamily of large GTPases which can be induced mainly by interferon gamma. [7]
GBP2 gene is located in a various compartment in the cell: nucleus, cytosol and cytoskeleton and also the dimer GBP2-GBP5 localise to the Golgi apparatus. [8]
In addition, the Isoprenylation is required to regulate the intracellular localization and the membrane association of GBP2. [9]
The murine GBP2 gene is not just highly activated by the interferon-gamma during macrophages activation but also by the stimulation of Toll-like receptors, Tumor necrosis factor (TNF) and Interleukin 1 beta. [10]
After the stimulation of interferon gamma, GPB2 murine is expressed in the innate and adaptive immune cells. [11]
Sequence analysis of GBP2 showed the presence of an RNA binding domain which comprises a three RNA recognition motifs (RRM) and SR domain. The amino terminus of GBp2 shares a four Arg-Gly-Gly (RGG) repeat motifs and nine serine residues in the context of arginine/serine motifs. [12]
The SR domain of GBP2 is a phosphorylation site for SR specific protein kinase SRPK (sky1) which lead a nuclear localization of GBP2. [12]
The porcine GBP2 present a high similarity regarding the N-terminal which present a globular domain and contain the GTPase function. However, the C-terminal present a helical domain which is less conserved. [13]
GBP2 gene can interact with the RNA via the domain RRM1 and RRM2. The RRM2 domain can recognize the core motif GGUC present in the RNA. Besides, a new type of RRM domain are identified and can interact with THO/TREX complex. [14]
GBp2 gene can cooperate with TREX (transcription- export) complex; a multimeric complex has different transcription factor and exports factors such as Yra1 and Sub2. [14]
Interferons are cytokines that have antiviral effects and inhibit tumor cell proliferation. They induce a large number of genes in their target cells, including those coding for the guanylate-binding proteins (GBPs). GBPs are characterized by their ability to specifically bind guanine nucleotides (GMP, GDP, and GTP). The protein encoded by this gene is a GTPase that converts GTP to GDP and GMP. [6] In addition, GBP2 gene can be a relationship between cell surface receptor and intracellular effectors which can transmit extracellular information into the cells as well as an intracellular signal transduction protein. [15]
A study on the bovine GBP2 gene showed the importance of GBP2 in the regulation of cell proliferation and the resistance to the pathogen infection such as an Exhibition of antiviral activity against influenza virus. [11]
GPB2 Promote an oxidative killing and deliver antimicrobial peptides to autophagolysosoma l, providing broad host protection against different pathogen classes. During a viral infection, GBPs Family(GBP1, GBP2 and GBP5) play a vital role to activate canonical and non-canonical inflammasome to response to a pathogen infection via chlamydia muridarum. [16]
A missense mutation of the GBP2 (A907G) has been identified in patients of a migraine. In the first step can lead to vasomotor dysfunction and then headaches. [15]
GBP2 is considered as a control factor for the proliferation and spreading in the tumor cell. The high expression of GBP2 is associated with a better diagnosis of breast cancer. P53 can upregulate GBP2 and play an essential role in the tumor development by inhibition of metalloproteinase MM9 as well as NF-Kappa B and Rac protein. [17]
The transcriptional level of GBP2 is also regulated by two transcription factor STAT1 and IRF1. GBP2 expression have a strong correlation with T cell metagene which seems an association with the infiltration of T cell in the breast cancer. [17]
However, a recent study showed that GBP2 can regulate dynamin-related protein 1 (Drp1) to block the translocation of Drp1 to the mitochondria which lead to an attenuation of the Drp1 dependent mitochondrial fission and also an invasion of breast cancer cells. [18]
RNA-binding proteins are proteins that bind to the double or single stranded RNA in cells and participate in forming ribonucleoprotein complexes. RBPs contain various structural motifs, such as RNA recognition motif (RRM), dsRNA binding domain, zinc finger and others. They are cytoplasmic and nuclear proteins. However, since most mature RNA is exported from the nucleus relatively quickly, most RBPs in the nucleus exist as complexes of protein and pre-mRNA called heterogeneous ribonucleoprotein particles (hnRNPs). RBPs have crucial roles in various cellular processes such as: cellular function, transport and localization. They especially play a major role in post-transcriptional control of RNAs, such as: splicing, polyadenylation, mRNA stabilization, mRNA localization and translation. Eukaryotic cells express diverse RBPs with unique RNA-binding activity and protein–protein interaction. According to the Eukaryotic RBP Database (EuRBPDB), there are 2961 genes encoding RBPs in humans. During evolution, the diversity of RBPs greatly increased with the increase in the number of introns. Diversity enabled eukaryotic cells to utilize RNA exons in various arrangements, giving rise to a unique RNP (ribonucleoprotein) for each RNA. Although RBPs have a crucial role in post-transcriptional regulation in gene expression, relatively few RBPs have been studied systematically.It has now become clear that RNA–RBP interactions play important roles in many biological processes among organisms.
Interferon-stimulated gene 15 (ISG15) is a 17 kDA secreted protein that in humans is encoded by the ISG15 gene. ISG15 is induced by type I interferon (IFN) and serves many functions, acting both as an extracellular cytokine and an intracellular protein modifier. The precise functions are diverse and vary among species but include potentiation of Interferon gamma (IFN-II) production in lymphocytes, ubiquitin-like conjugation to newly-synthesized proteins and negative regulation of the IFN-I response.
DnaJ homolog subfamily A member 3, mitochondrial, also known as Tumorous imaginal disc 1 (TID1), is a protein that in humans is encoded by the DNAJA3 gene on chromosome 16. This protein belongs to the DNAJ/Hsp40 protein family, which is known for binding and activating Hsp70 chaperone proteins to perform protein folding, degradation, and complex assembly. As a mitochondrial protein, it is involved in maintaining membrane potential and mitochondrial DNA (mtDNA) integrity, as well as cellular processes such as cell movement, growth, and death. Furthermore, it is associated with a broad range of diseases, including neurodegenerative diseases, inflammatory diseases, and cancers.
ELAV-like protein 1 or HuR is a protein that in humans is encoded by the ELAVL1 gene.
RhoC is a small signaling G protein, and is a member of the Rac subfamily of the family Rho family of GTPases. It is encoded by the gene RHOC.
Steroid receptor RNA activator 1 also known as steroid receptor RNA activator protein (SRAP) is a protein that in humans is encoded by the SRA1 gene. The mRNA transcribed from the SRA1 gene is a component of the ribonucleoprotein complex containing NCOA1. This functional RNA also encodes a protein.
Nucleolysin TIAR is a protein that in humans is encoded by the TIAL1 gene.
Deleted in Liver Cancer 1 also known as DLC1 and StAR-related lipid transfer protein 12 (STARD12) is a protein which in humans is encoded by the DLC1 gene.
CUGBP, Elav-like family member 2, also known as Etr-3 is a protein that in humans is encoded by the CELF2 gene.
Interferon-induced guanylate-binding protein 1 is a protein that in humans is encoded by the GBP1 gene. It belongs to the dynamin superfamily of large GTPases.
N-myc-interactor also known as N-myc and STAT interactor is a protein that in humans is encoded by the NMI gene.
Tripartite motif-containing protein 25 is a protein that in humans is encoded by the TRIM25 gene.
Rnd2 is a small signaling G protein, and is a member of the Rnd subgroup of the Rho family of GTPases. It is encoded by the gene RND2.
Interferon-induced transmembrane protein 1 is a protein that in humans is encoded by the IFITM1 gene. IFITM1 has also recently been designated CD225. This protein has several additional names: fragilis, IFI17 [interferon-induced protein 17], 9-27 [Interferon-inducible protein 9-27] and Leu13.
Putative RNA-binding protein 3 is a protein that in humans is encoded by the RBM3 gene.
59 kDa 2'-5'-oligoadenylate synthetase-like protein is an enzyme that in humans is encoded by the OASL gene.
Immunity Related Guanosine Triphosphatases or IRGs are proteins activated as part of an early immune response. IRGs have been described in various mammals but are most well characterized in mice. IRG activation in most cases is induced by an immune response and leads to clearance of certain pathogens.
In molecular biology, the guanylate-binding proteins family is a family of GTPases that is induced by interferon (IFN)-gamma. GTPases induced by IFN-gamma are key to the protective immunity against microbial and viral pathogens. These GTPases are classified into three groups: the small 47-KD immunity-related GTPases (IRGs), the Mx proteins, and the large 65- to 67-kd GTPases. Guanylate-binding proteins (GBP) fall into the last class.
Stimulator of interferon genes (STING), also known as transmembrane protein 173 (TMEM173) and MPYS/MITA/ERIS is a protein that in humans is encoded by the STING1 gene.
The TREX (TRanscription-EXport) complex is a conserved eukaryotic multi-protein complex that couples mRNA transcription and nuclear export. The TREX complex travels across transcribed genes with RNA polymerase II. TREX binds mRNA and recruits transport proteins NXF1 and NXT1, which shuttle the mRNA out of the nucleus. The TREX complex plays an important role in genome stability and neurodegenerative diseases.
