scholarly journals The FAM83 family of proteins: from pseudo-PLDs to anchors for CK1 isoforms

2018 ◽  
Vol 46 (3) ◽  
pp. 761-771 ◽  
Author(s):  
Polyxeni Bozatzi ◽  
Gopal P. Sapkota

The eight members of the FAM83 (FAMily with sequence similarity 83) family of poorly characterised proteins are only present in vertebrates and are defined by the presence of the conserved DUF1669 domain of unknown function at their N-termini. The DUF1669 domain consists of a conserved phospholipase D (PLD)-like catalytic motif. However, the FAM83 proteins display no PLD catalytic (PLDc) activity, and the pseudo-PLDc motif present in each FAM83 member lacks the crucial elements of the native PLDc motif. In the absence of catalytic activity, it is likely that the DUF1669 domain has evolved to espouse novel function(s) in biology. Recent studies have indicated that the DUF1669 domain mediates the interaction with different isoforms of the CK1 (casein kinase 1) family of Ser/Thr protein kinases. In turn, different FAM83 proteins, which exhibit unique amino acid sequences outside the DUF1669 domain, deliver CK1 isoforms to unique subcellular compartments. One of the first protein kinases to be discovered, the CK1 isoforms are thought to be constitutively active and are known to control a plethora of biological processes. Yet, their regulation of kinase activity, substrate selectivity and subcellular localisation has remained a mystery. The emerging evidence now supports a central role for the DUF1669 domain, and the FAM83 proteins, in the regulation of CK1 biology.

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Suresh Subramani ◽  
Saranya Jayapalan ◽  
Raja Kalpana ◽  
Jeyakumar Natarajan

HomoKinase database is a comprehensive collection of curated human protein kinases and their relevant biological information. The entries in the database are curated by three criteria: HGNC approval, gene ontology-based biological process (protein phosphorylation), and molecular function (ATP binding and kinase activity). For a given query protein kinase name, the database provides its official symbol, full name, other known aliases, amino acid sequences, functional domain, gene ontology, pathways assignments, and drug compounds. In addition, as a search tool, it enables the retrieval of similar protein kinases with specific family, subfamily, group, and domain combinations and tabulates the information. The present version contains 498 curated human protein kinases and links to other popular databases.


2014 ◽  
Vol 460 (2) ◽  
pp. 141-156 ◽  
Author(s):  
Andrea Venerando ◽  
Maria Ruzzene ◽  
Lorenzo A. Pinna

The term ‘casein kinase’ has been widely used for decades to denote protein kinases sharing the ability to readily phosphorylate casein in vitro. These fall into three main classes: two of them, later renamed as protein kinases CK1 (casein kinase 1, also known as CKI) and CK2 (also known as CKII), are pleiotropic members of the kinome functionally unrelated to casein, whereas G-CK, or genuine casein kinase, responsible for the phosphorylation of casein in the Golgi apparatus of the lactating mammary gland, has only been identified recently with Fam20C [family with sequence similarity 20C; also known as DMP-4 (dentin matrix protein-4)], a member of the four-jointed family of atypical protein kinases, being responsible for the phosphorylation of many secreted proteins. In hindsight, therefore, the term ‘casein kinase’ is misleading in every instance; in the case of CK1 and CK2, it is because casein is not a physiological substrate, and in the case of G-CK/Fam20C/DMP-4, it is because casein is just one out of a plethora of its targets, and a rather marginal one at that. Strikingly, casein kinases altogether, albeit representing a minimal proportion of the whole kinome, appear to be responsible for the generation of up to 40–50% of non-redundant phosphosites currently retrieved in human phosphopeptides database. In the present review, a short historical explanation will be provided accounting for the usage of the same misnomer to denote three unrelated classes of protein kinases, together with an update of our current knowledge of these pleiotropic enzymes, sharing the same misnomer while playing very distinct biological roles.


2012 ◽  
Vol 23 (1) ◽  
pp. 22-35 ◽  
Author(s):  
Barbara Widmann ◽  
Franziska Wandrey ◽  
Lukas Badertscher ◽  
Emanuel Wyler ◽  
Jens Pfannstiel ◽  
...  

RIO proteins form a conserved family of atypical protein kinases. Humans possess three distinct RIO kinases—hRio1, hRio2, and hRio3, of which only hRio2 has been characterized with respect to its role in ribosomal biogenesis. Here we show that both hRio1 and hRio3, like hRio2, are associated with precursors of 40S ribosomal subunits in human cells. Furthermore, we demonstrate that depletion of hRio1 by RNA interference affects the last step of 18S rRNA maturation and causes defects in the recycling of several trans-acting factors (hEnp1, hRio2, hLtv1, hDim2/PNO1, and hNob1) from pre-40S subunits in the cytoplasm. Although the effects of hRio1 and hRio2 depletion are similar, we show that the two kinases are not fully interchangeable. Moreover, rescue experiments with a kinase-dead mutant of hRio1 revealed that the kinase activity of hRio1 is essential for the recycling of the endonuclease hNob1 and its binding partner hDim2 from cytoplasmic pre-40S. Kinase-dead hRio1 is trapped on pre-40S particles containing hDim2 and hNob1 but devoid of hEnp1, hLtv1, and hRio2. These data reveal a role of hRio1 in the final stages of cytoplasmic pre-40S maturation.


2005 ◽  
Vol 391 (2) ◽  
pp. 409-415 ◽  
Author(s):  
Anna Kärkönen ◽  
Alain Murigneux ◽  
Jean-Pierre Martinant ◽  
Elodie Pepey ◽  
Christophe Tatout ◽  
...  

UDPGDH (UDP-D-glucose dehydrogenase) oxidizes UDP-Glc (UDP-D-glucose) to UDP-GlcA (UDP-D-glucuronate), the precursor of UDP-D-xylose and UDP-L-arabinose, major cell wall polysaccharide precursors. Maize (Zea mays L.) has at least two putative UDPGDH genes (A and B), according to sequence similarity to a soya bean UDPGDH gene. The predicted maize amino acid sequences have 95% similarity to that of soya bean. Maize mutants with a Mu-element insertion in UDPGDH-A or UDPGDH-B were isolated (udpgdh-A1 and udpgdh-B1 respectively) and studied for changes in wall polysaccharide biosynthesis. The udpgdh-A1 and udpgdh-B1 homozygotes showed no visible phenotype but exhibited 90 and 60–70% less UDPGDH activity respectively than wild-types in a radiochemical assay with 30 μM UDP-glucose. Ethanol dehydrogenase (ADH) activity varied independently of UDPGDH activity, supporting the hypothesis that ADH and UDPGDH activities are due to different enzymes in maize. When extracts from wild-types and udpgdh-A1 homozygotes were assayed with increasing concentrations of UDP-Glc, at least two isoforms of UDPGDH were detected, having Km values of approx. 380 and 950 μM for UDP-Glc. Leaf and stem non-cellulosic polysaccharides had lower Ara/Gal and Xyl/Gal ratios in udpgdh-A1 homozygotes than in wild-types, whereas udpgdh-B1 homozygotes exhibited more variability among individual plants, suggesting that UDPGDH-A activity has a more important role than UDPGDH-B in UDP-GlcA synthesis. The fact that mutation of a UDPGDH gene interferes with polysaccharide synthesis suggests a greater importance for the sugar nucleotide oxidation pathway than for the myo-inositol pathway in UDP-GlcA biosynthesis during post-germinative growth of maize.


2001 ◽  
Vol 21 (15) ◽  
pp. 5109-5121 ◽  
Author(s):  
Yann-Gaël Gangloff ◽  
Jean-Christophe Pointud ◽  
Sylvie Thuault ◽  
Lucie Carré ◽  
Christophe Romier ◽  
...  

ABSTRACT The RNA polymerase II transcription factor TFIID comprises the TATA binding protein (TBP) and a set of TBP-associated factors (TAFIIs). TFIID has been extensively characterized for yeast, Drosophila, and humans, demonstrating a high degree of conservation of both the amino acid sequences of the constituent TAFIIs and overall molecular organization. In recent years, it has been assumed that all the metazoan TAFIIs have been identified, yet no metazoan homologues of yeast TAFII47 (yTAFII47) and yTAFII65 are known. Both of these yTAFIIs contain a histone fold domain (HFD) which selectively heterodimerizes with that of yTAFII25. We have cloned a novel mouse protein, TAFII140, containing an HFD and a plant homeodomain (PHD) finger, which we demonstrated by immunoprecipitation to be a mammalian TFIID component. TAFII140 shows extensive sequence similarity toDrosophila BIP2 (dBIP2) (dTAFII155), which we also show to be a component of DrosophilaTFIID. These proteins are metazoan homologues of yTAFII47 as their HFDs selectively heterodimerize with dTAFII24 and human TAFII30, metazoan homologues of yTAFII25. We further show that yTAFII65 shares two domains with theDrosophila Prodos protein, a recently described potential dTAFII. These conserved domains are critical for yTAFII65 function in vivo. Our results therefore identify metazoan homologues of yTAFII47 and yTAFII65.


2021 ◽  
Author(s):  
Carsten Grupstra ◽  
Lauren I Howe-Kerr ◽  
Alex J Veglia ◽  
Reb L Bryant ◽  
Samantha R Coy ◽  
...  

Climate change-driven ocean warming is increasing the frequency and severity of bleaching events, in which corals appear whitened after losing their dinoflagellate endosymbionts (family Symbiodiniaceae). Viral infections of Symbiodiniaceae may contribute to some bleaching signs, but little empirical evidence exists to support this hypothesis. We present the first temporal analysis of a viral lineage-the Symbiodiniaceae-infecting 'dinoRNAVs'-in coral colonies exposed to a 5-day heat treatment. Throughout the experiment, all colonies were dominated by Symbiodiniaceae in the genus Cladocopium, but 124 dinoRNAV major capsid protein 'aminotypes' (unique amino acid sequences) were detected across coral genets and treatments. Seventeen dinoRNAV aminotypes were found only in heat-treated fragments, and 22 aminotypes were detected at higher relative abundances in heat-treated fragments. DinoRNAVs also exhibited higher alpha diversity and dispersion under heat stress. Together, these findings provide the first empirical evidence that exposure to high temperatures triggers some dinoRNAVs to switch from a persistent to a productive infection mode within heat-stressed corals. Over extended time frames, we hypothesize that cumulative dinoRNAV lysis of Symbiodiniaceae cells during productive infections could decrease Symbiodiniaceae densities within corals, observable as bleaching signs. This study sets the stage for reef-scale investigations of dinoRNAV dynamics during bleaching events.


Author(s):  
Najma Rachidi ◽  
Uwe Knippschild ◽  
Gerald F. Späth

Casein Kinase 1 (CK1) family members are serine/threonine protein kinases that are involved in many biological processes and highly conserved in eukaryotes from protozoan to humans. Even though pathogens exploit host CK1 signaling pathways to survive, the role of CK1 in infectious diseases and host/pathogen interaction is less well characterized compared to other diseases, such as cancer or neurodegenerative diseases. Here we present the current knowledge on CK1 in protozoan parasites highlighting their essential role for parasite survival and their importance for host-pathogen interactions. We also discuss how the dual requirement of CK1 family members for parasite biological processes and host subversion could be exploited to identify novel antimicrobial interventions.


2021 ◽  
Vol 11 ◽  
Author(s):  
Xiaowen Xu ◽  
Meifeng Li ◽  
Zeyuan Deng ◽  
Jihuan Hu ◽  
Zeyin Jiang ◽  
...  

Accumulating evidence indicates that mammalian NIMA (never in mitosis, gene A)-related kinase 6 (NEK6) plays potential roles during the course of tumorigenesis, but little is known about NEK6 in lower vertebrates. Herein, we reported a mammalian ortholog of NEK6 in grass carp (Ctenopharyngodon idellus) (CiNEK6). Multiple alignment of amino acid sequences and phylogenetic analysis showed that CiNEK6 shares a high level of sequence similarity with its counterparts in birds. CiNEK6 was ubiquitously expressed in all tested tissues, and its expression level was increased under treatment with GCRV (dsRNA virus) or poly I:C (dsRNA analog). Q-PCR and dual-luciferase assays suggested that CiNEK6 overexpression suppressed IFN I activity in CIK cells treated with poly I:C. Knockdown of CiNEK6 resulted in a higher level of IFN I expression in CIK cells treated with poly I:C compared to those which received PBS. Interestingly, analysis of subcellular localization demonstrated that CiNEK6 protein scattered throughout the cytoplasm is gradually congregated together at the edges of karyotheca upon stimulation with poly I:C. Co-IP and co-localization assays suggested that CiNEK6 interacts with CiIRF3 after poly I:C challenge. In poly I:C-treated cells, the phosphorylation of CiIRF3 was increased by CiNEK6 knockdown, but was suppressed by CiNEK6 overexpression, suggesting that CiNEK6 decreases IFN I expression through inhibiting CiIRF3 activity. Cell viability assay, crystal violet staining, and detection of Vp5 also showed that CiNEK6 plays an inhibitory role in IRF3-mediated antiviral responses.


Author(s):  
Sona. S Dev ◽  
P. Poornima ◽  
Akhil Venu

Eggplantor brinjal (Solanum melongena L.), is highly susceptible to various soil-borne diseases. The extensive use of chemical fungicides to combat these diseases can be minimized by identification of resistance gene analogs (RGAs) in wild species of cultivated plants.In the present study, degenerate PCR primers for the conserved regions ofnucleotide binding site-leucine rich repeat (NBS-LRR) were used to amplify RGAs from wild relatives of eggplant (Black nightshade (Solanum nigrum), Indian nightshade (Solanumviolaceum)and Solanu mincanum) which showed resistance to the bacterial wilt pathogen, Ralstonia solanacearumin the preliminary investigation. The amino acid sequence of the amplicons when compared to each other and to the amino acid sequences of known RGAs deposited in Gen Bank revealed significant sequence similarity. The phylogenetic analysis indicated that they belonged to the toll interleukin-1 receptors (TIR)-NBS-LRR type R-genes. Multiple sequence alignment with other known R genes showed significant homology with P-loop, Kinase 2 and GLPL domains of NBS-LRR class genes. There has been no report on R genes from these wild eggplants and hence the diversity analysis of these novel RGAs can lead to the identification of other novel R genes within the germplasm of different brinjal plants as well as other species of Solanum.


Microbiology ◽  
2009 ◽  
Vol 155 (6) ◽  
pp. 1966-1976 ◽  
Author(s):  
Jan R. van der Ploeg

Clustered regularly interspaced short palindromic repeats (CRISPR) consist of highly conserved direct repeats interspersed with variable spacer sequences. They can protect bacteria against invasion by foreign DNA elements. The genome sequence of Streptococcus mutans strain UA159 contains two CRISPR loci, designated CRISPR1 and CRISPR2. The aims of this study were to analyse the organization of CRISPR in further S. mutans strains and to investigate the importance of CRISPR in acquired immunity to M102-like phages. The sequences of CRISPR1 and CRISPR2 arrays were determined for 29 S. mutans strains from different persons. More than half of the CRISPR1 spacers and about 35 % of the CRISPR2 spacers showed sequence similarity with the genome sequence of M102, a virulent siphophage specific for S. mutans. Although only a few spacers matched the phage sequence completely, most of the mismatches had no effect on the amino acid sequences of the phage-encoded proteins. The results suggest that S. mutans is often attacked by M102-like bacteriophages, and that its acquisition of novel phage-derived CRISPR sequences goes along with the presence of S. mutans phages in the environment. Analysis of CRISPR1 of M102-resistant mutants of S. mutans OMZ 381 showed that some of them had acquired novel spacers, and the sequences of all but one of these matched the phage M102 genome sequence. This suggests that the acquisition of the spacers contributed to the resistance against phage infection. However, since not all resistant mutants had new spacers, and since the removal of the CRISPR1 array in one of the mutants and in wild-type strains did not lead to loss of resistance to infection by M102, the acquisition of resistance must be based on further elements as well.


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