241 human active and 13 inactive phosphatases in total;
194 phosphatases have substrate data;
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336 protein substrates;
83 non-protein substrates;
1215 dephosphorylation interactions;
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299 KEGG pathways;
876 Reactome pathways;
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last scientific update: 11 Mar, 2019
last maintenance update: 01 Sep, 2023
Cytoplasm Nucleusspeckle Note=In nuclear speckles Shuttlesbetween the nucleus and the cytoplasm
Function (UniProt annotation)
Plays a role in preventing exon skipping, ensuring theaccuracy of splicing and regulating alternative splicingInteracts with other spliceosomal components, via the RS domains,to form a bridge between the 5'- and 3'-splice site bindingcomponents, U1 snRNP and U2AF Can stimulate binding of U1 snRNPto a 5'-splice site-containing pre-mRNA Binds to purine-rich RNAsequences, either the octamer, 5'-RGAAGAAC-3' (r=A or G) or thedecamers, AGGACAGAGC/AGGACGAAGC Binds preferentially to the 5'-CGAGGCG-3' motif in vitro Three copies of the octamer constitutea powerful splicing enhancer in vitro, the ASF/SF2 splicingenhancer (ASE) which can specifically activate ASE-dependentsplicing Isoform ASF-2 and isoform ASF-3 act as splicingrepressors May function as export adapter involved in mRNAnuclear export through the TAP/NXF1 pathway
After transcription, eukaryotic mRNA precursors contain protein-coding exons and noncoding introns. In the following splicing, introns are excised and exons are joined by a macromolecular complex, the spliceosome. The standard spliceosome is made up of five small nuclear ribonucleoproteins (snRNPs), U1, U2, U4, U5, and U6 snRNPs, and several spliceosome-associated proteins (SAPs). Spliceosomes are not a simple stable complex, but a dynamic family of particles that assemble on the mRNA precursor and help fold it into a conformation that allows transesterification to proceed. Various spliceosome forms (e.g. A-, B- and C-complexes) have been identified.
The interleukin 17 (IL-17) family, a subset of cytokines consisting of IL-17A-F, plays crucial roles in both acute and chronic inflammatory responses. IL-17A, the hallmark cytokine of the newly defined T helper 17 (TH17) cell subset, has important roles in protecting the host against extracellular pathogens, but also promotes inflammatory pathology in autoimmune disease, whereas IL-17F is mainly involved in mucosal host defense mechanisms. IL-17E (IL-25) is an amplifier of Th2 immune responses. IL-17C has biological functions similar to those of IL-17A. The functions of IL-17B and IL-17D remain largely elusive. The IL-17 family signals via their correspondent receptors and activates downstream pathways that include NF-kappaB, MAPKs and C/EBPs to induce the expression of antimicrobial peptides, cytokines and chemokines. The receptor proximal adaptor Act1 (an NF-kappaB activator 1) is considered as the master mediator in IL-17A signaling. It is likely that Act1 is a common signal adaptor also shared by other members mediated signalings in this family.
Herpes simplex virus 1(HSV-1) is a common human pathogen, which initially infects orofacial mucosal surfaces. The virus replicates in epithelial cells at these sites, causing clinically overt disease characterized by vesicular lesions. HSV-1 then penetrates to the nervous system and establishes latency in sensory neurons. Throughout the lifetime of the host, HSV-1 may reactivate from its latent state and reinitiate a lytic infection cycle. HSV-1 has developed various mechanisms to escape its host innate immune responses and increased its capacity to replicate and to persist. ICP34.5, ICP0, ICP27, Us11 and Vhs (UL41) are the proteins involved in viral interference.
Transport of mRNA from the nucleus to the cytoplasm, where it is translated into protein, is highly selective and closely coupled to correct RNA processing. This coupling is achieved by the nuclear pore complex, which recognizes and transports only completed mRNAs
The splicing of pre-mRNA occurs within a large, very dynamic complex, designated the 'spliceosome'. The 50-60S spliceosomes are estimated to be 40-60 nm in diameter, and have molecular weights in the range of 3-5 million kDa. Small nuclear RNAs (snRNAs) U1, U2, U4, U5, and U6, are some of the best characterized components of spliceosomes, and are known to play key roles not only in spliceosomal assembly, but also in the two catalytic steps of the splicing reaction. Over 150 proteins have been detected in spliceosomes, and only a subset of these has been characterized. The characterization, and the determination of the functions of the protein components of the spliceosome, is still work in progress.
During spliceosome assembly, the snRNAs and the spliceosomal proteins assemble on the pre-mRNA in a stepwise pathway. First the E complex forms, followed by complexes A and B; the C complex forms next and contains the products of the first step of the splicing reaction. Complexes called i and D form as a consequence of the second step of the splicing reaction, which contain the excised intron and the spliced exons, respectively
The splicing of a subset of pre-mRNA introns occurs by a second pathway, designated the AT-AC or U12-dependent splicing pathway. AT-AC introns have highly conserved, non-canonical splice sites that are removed by the AT-AC spliceosome, which contains distinct snRNAs (U11, U12, U4atac, U6atac) that are structurally and functionally analogous to the major spliceosome. U5 snRNA as well as many of the protein factors appear to be conserved between the two spliceosomes
The 3' ends of eukaryotic mRNAs are generated by posttranscriptional processing of an extended primary transcript. For almost all RNAs, 3'-end processing consists of two steps: (i) the mRNA is first cleaved at a particular phosphodiester bond downstream of the coding sequence, (ii) the upstream fragment then receives a poly(A) tail of approximately 250 adenylate residues, whereas the downstream fragment is degraded. The two partial reactions are coupled so that reaction intermediates are usually undetectable. While 3' processing can be studied as an isolated event in vitro, it appears to be connected to transcription, splicing, and transcription termination in vivo.
The only known exception to the rule of cleavage followed by polyadenylation are the major histone mRNAs, which are cleaved but not polyadenylated