The cyanobacterial circadian clock protein KaiB is encoded in the kaiABC operon that controls circadian rhythms. It is a component of the KaiABC clock protein complex, which constitutes the main circadian regulator in cyanobacteria [, ]. KaiB forms homodimers, homotetramers, and multimeric complexes with KaiA and/or KaiC [, ]. KaiB-KaiC binding is accompanied by a dramatic reduction in KaiC phosphorylation and followed by dissociation of the clock protein complex [].
The cyanobacterial circadian clock protein KaiB is encoded in the kaiABC operon that controls circadian rhythms. It is a component of the KaiABC clock protein complex, which constitutes the main circadian regulator in cyanobacteria [, , ]. KaiB has homologues of unknown function in some Archaea and Proteobacteria, and paralogs of unknown function in some Cyanobacteria. KaiB forms homodimers, homotetramers, and multimeric complexes with KaiA and/or KaiC [].
The circadian clock protein KaiC, is encoded in the kaiABC operon that controls circadian rhythms and may be universal inCyanobacteria. Each member contains two copies of the KaiC domain, which is alsofound in other proteins. KaiC performs autophosphorylation and acts as its own transcriptional repressor. Kai proteins (KaiA and KaiC) appear to positively and negatively regulate kaiBC transcription which is consistent with a transcription/translation oscillatory (TTO) feedback model, believed to be at the core of all self-sustained circadian timers. However, the cyanobacterial circadian clock is able to function without de novo synthesis of clock gene mRNAs and the clock proteins, and the period is accurately determined without TTO feedback and the system is also temperature-compensated. It has been demonstrated that these three purified proteins form a temperature-compensated molecular oscillator in vitro that exhibits rhythmic phosphorylation and dephosphorylation of KaiC[].A negative-stain electron microscopy study of Synechococcus elongatus (Thermosynechococcus elongatus) and Thermosynechococcus elongatus BP-1 KaiA-KaiC complexes in combination with site-directed mutagenesis reveals that KaiA binds exclusively to the CII half of the KaiC hexamer. The EM-based model of the KaiA-KaiC complex reveals protein-protein interactions at two sites: the known interaction of the flexible C-terminal KaiC peptide with KaiA, and a second postulated interaction between the apical region of KaiA and the ATP binding cleft on KaiC. This model brings KaiA mutation sites that alter clock period or abolish rhythmicity into contact with KaiC and suggests how KaiA might regulate KaiC phosphorylation [].
Frequency (FRQ) is a key circadian clock component that is involved in the generation of biological rhythms in Neurospora crassa []. It plays a role in rhythm stability, period length, and temperature compensation. FRQ behaves as a negative element in the circadian transcriptional loop []. The protein has been shown to interact with itself via a coiled-coil [].
KaiA is a component of the kaiABC clock protein complex, which constitutes the main circadian regulator in cyanobacteria. The kaiABC complex may act as a promoter-nonspecific transcription regulator that represses transcription, possibly by acting on the state of chromosome compaction. In the complex, KaiA enhances the phosphorylation status of kaiC. In contrast, the presence of kaiB in the complex decreases the phosphorylation status of kaiC, suggesting that kaiB acts by antagonising the interaction between kaiA and kaiC. The activity of KaiA activates kaiBC expression, while KaiC represses it. The overall fold of the KaiA monomer is that of a four-helix bundle, which forms a dimer in the known structure []. KaiA functions as a homodimer. Each monomer is composed of three functional domains: the N-terminal amplitude-amplifier domain, the central period-adjuster domain and the C-termianl clock-oscillator domain. The N-terminal domain of KaiA, from cyanobacteria, acts as a psuedo-receiver domain, but lacks the conserved aspartyl residue required for phosphotransfer in response regulators []. The C-terminal domain is responsible for dimer formation, binding to KaiC, enhancing KaiC phosphorylation and generating the circadian oscillations []. The KaiA protein from Anabaena sp. (strain PCC 7120) lacks the N-terminal CheY-like domain.
This entry represents circadian clock protein kinase KaiC from bacteria and some uncharacterised KaiC-like proteins from archaea.The circadian clock protein KaiC, is encoded in the kaiABC operon that controls circadian rhythms and may be universal inCyanobacteria. Each member contains two copies of the KaiC domain, which is alsofound in other proteins. KaiC performs autophosphorylation and acts as its own transcriptional repressor. Kai proteins (KaiA and KaiC) appear to positively and negatively regulate kaiBC transcription which is consistent with a transcription/translation oscillatory (TTO) feedback model, believed to be at the core of all self-sustained circadian timers. However, the cyanobacterial circadian clock is able to function without de novo synthesis of clock gene mRNAs and the clock proteins, and the period is accurately determined without TTO feedback and the system is also temperature-compensated. It has been demonstrated that these three purified proteins form a temperature-compensated molecular oscillator in vitro that exhibits rhythmic phosphorylation and dephosphorylation of KaiC[].A negative-stain electron microscopy study of Synechococcus elongatus (Thermosynechococcus elongatus) and Thermosynechococcus elongatus BP-1 KaiA-KaiC complexes in combination with site-directed mutagenesis reveals that KaiA binds exclusively to the CII half of the KaiC hexamer. The EM-based model of the KaiA-KaiC complex reveals protein-protein interactions at two sites: the known interaction of the flexible C-terminal KaiC peptide with KaiA, and a second postulated interaction between the apical region of KaiA and the ATP binding cleft on KaiC. This model brings KaiA mutation sites that alter clock period or abolish rhythmicity into contact with KaiC and suggests how KaiA might regulate KaiC phosphorylation [].
This entry represents a rather narrowly distributed archaeal protein family in which members have a single copy of the KaiC domain. This stands in contrast to the circadian clock protein KaiC itself, with two copies of the domain. Members are expected to have weak ATPase activity, by homology to the autokinase/autophosphorylase KaiC itself.
This entry represents the C-terminal domain of Circadian clock protein KaiA.Cyanobacteria are the most primitive organisms known to exhibit circadianrhythms. KaiA, kaiB and kaiC constitute the circadian clockmachinery in cyanobacteria, and kaiA activates kaiBC expression whereas kaiCrepresses it []. Apparent homologues of kaiB and kaiC are found among noncyanobacterial eubacteria and the archaea. However kaiA appears confined within the cyanobacteria, which are the only prokaryotes with demonstrated circadian rhythms [].There are at least two types of kaiA proteins: long and short []. The long versions consist of ~300 aminoacyl residues. There is limited sequence conservation in the amino-terminal 200 residues of these proteins but a high degree of conservation in the carboxyl-terminal 100 residues. They thus appear to contain two independently folded domains, the amino and carboxyl regions, connected by a canonical linker. The short versions are essentially independent carboxyl-terminal domains.The kaiA N-terminal domain consists of a central five-stranded (beta1 tobeta5) parallel β-sheet flanked by two groups of α-helices (alpha1,alpha4 and alpha2, alpha3) packed on either side of the β-sheet and anadditional alpha helix (alpha5) lying near the amino terminus of the centralβ-strand [, ]. The structure of the N-terminal domain ofkaiA is that of a pseudo-receiver domain, similar to those found in bacterialresponse regulators. Although the fold is that of a canonical receiver domain, the primary sequence is dissimilar, and it lacks theconserved aspartate residue necessary for phosphorylation. KaiA activationmost likely involves direct protein-protein interactions of the N-terminaldomain that result in functional modulation of the C-terminal effector domain.The C-terminal kaiA domain is reponsible for dimer formation, binding to kaiC,enhancing kaiC phosphorylation and generating the circadian oscillations. Itadopts a novel all α-helical homodimeric structure[, , , ]. The kaiA C-terminal domain contains two parallel helix-hairpin-helix motifs that form a four helix bundle, which represents a new proteinfolding motif.
This entry represents the N-terminal domain of KaiA. Cyanobacteria are the most primitive organisms known to exhibit circadianrhythms. KaiA, kaiB and kaiC constitute the circadian clockmachinery in cyanobacteria, and kaiA activates kaiBC expression whereas kaiCrepresses it []. Apparent homologues of kaiB and kaiC are found amongnoncyanobacterial eubacteria and the archaea. However kaiA appears confinedwithin the cyanobacteria, which are the only prokaryotes with demonstratedcircadian rhythms [].There are at least two types of kaiA proteins: long and short []. The longversions consist of ~300 aminoacyl residues. There is limited sequenceconservation in the amino-terminal 200 residues of these proteins but a highdegree of conservation in the carboxyl-terminal 100 residues. They thus appearto contain two independently folded domains, the amino and carboxyl regions,connected by a canonical linker. The short versions are essentiallyindependent carboxyl-terminal domains.The kaiA N-terminal domain consists of a central five-stranded (beta1 tobeta5) parallel β-sheet flanked by two groups of α-helices (alpha1,alpha4 and alpha2, alpha3) packed on either side of the β-sheet and anadditional alpha helix (alpha5) lying near the amino terminus of the centralβ-strand [, ]. The structure of the N-terminal domain ofkaiA is that of a pseudo-receiver domain, similar to those found in bacterialresponse regulators. Although the fold is that of a canonical receiver domain, the primary sequence is dissimilar, and it lacks theconserved aspartate residue necessary for phosphorylation. KaiA activationmost likely involves direct protein-protein interactions of the N-terminaldomain that result in functional modulation of the C-terminal effector domain.The C-terminal kaiA domain is reponsible for dimer formation, binding to kaiC,enhancing kaiC phosphorylation and generating the circadian oscillations. Itadopts a novel all α-helical homodimeric structure[, , , ]. The kaiA C-terminal domain contains two parallel helix-hairpin-helix motifs that form a four helix bundle, which represents a new proteinfolding motif.
Protein EARLY FLOWERING 4 is a component of the central CCA1/LHY-TOC1 feedback loop in the circadian clock that promotes clock accuracy and is required for sustained rhythms in the absence of daily light/dark cycles [, ].
Members of this entry are archaeal single-domain KaiC_related proteins, homologous to the Cyanobacterial circadian clock cycle protein KaiC, an autokinase/autophosphorylase that has two copies of the domain.
Protein EARLY FLOWERING 4 is a component of the central CCA1/LHY-TOC1 feedback loop in the circadian clock that promotes clock accuracy and is required for sustained rhythms in the absence of daily light/dark cycles [, ].This domain forms an α-helical homodimer in ELF4 proteins.
Members of this family contain a single copy of the KaiC domain that occurs in two copies of the circadian clock protein kinase KaiC itself. Members occur primarily in archaea and in Thermotogales.
This entry represents a domain found in KaiC, which is a core component of the KaiBC clock protein complex that constitutes the main circadian regulator in cyanobacteria []. The circadian clock protein KaiC, is encoded in the kaiABC operon that controls circadian rhythms and may be universal in Cyanobacteria. Each member contains two copies of this domain, which is alsofound in other proteins. KaiC performs autophosphorylation and acts as its own transcriptional repressor.Proteins containing this domain also include some eukrayotic proteins.
The LNK family consists of light and clock regulated morning genes from plants. These control both the pace of circadian rhythms and the photoperiodic regulation of flowering time by promoting the expression of a subset of clock and flowering time genes in the afternoon []. The LCL domain of clock-related factor REVEILLE8 recruits LNKs to target promoters, while its MYB domain provides DNA binding specificity. In turn, LNKs interact with RNA Polymerase II and the transcript elongation FACT complex, resulting in rhythmic changes of gene expression [].
This entry represents the adaptive-response sensory-kinase sasA family which may be involved in signal transduction. This family of proteins participate in the kaiABC clock protein complex, which constitutes the main circadian regulator in cyanobacteria, via its interaction with kaiC []. The kaiABC complex has a core comprising a kaiC homohexamer, a kaiB dimer and two kaiA dimers. The adaptive-response sensory-kinase sasA is required for robustness of the circadian rhythm of gene expression and is involved in clock outputs. The proteins contain a histidine kinase domain.
Circadian-associated transcriptional repressor (Ciart or Chrono) is a negative regulatory component of the circadian clock [, , ]. It functions as a transcriptional repressor, modulating BMAL1-CLOCK activity. It also regulates metabolic pathways such as the glucocorticoid response triggered by behavioral stress [].
Nuclear receptor-interacting protein 1 (also known as nuclear factor RIP140) modulates transcriptional activation by steroid receptors such as NR3C1, NR3C2 and ESR1 []. It also modulates transcriptional repression by nuclear hormone receptors []and clock gene expression []. It consists of four distinct autonomous repression domains [].This domain is the fourth (C-terminal) repression domain of nuclear receptor-interacting protein 1 [, ].
Nuclear receptor-interacting protein 1 (also known as nuclear factor RIP140) modulates transcriptional activation by steroid receptors such as NR3C1, NR3C2 and ESR1 []. It also modulates transcriptional repression by nuclear hormone receptors []and clock gene expression []. It consists of four distinct autonomous repression domains [].This domain is the third repression domain of nuclear receptor-interacting protein 1 [, ].
Nuclear receptor-interacting protein 1 (also known as nuclear factor RIP140) modulates transcriptional activation by steroid receptors such as NR3C1, NR3C2 and ESR1 []. It also modulates transcriptional repression by nuclear hormone receptors []and clock gene expression []. It consists of four distinct autonomous repression domains [].This domain is the second repression domain of nuclear receptor-interacting protein 1 [, ].
Nuclear receptor-interacting protein 1 (also known as nuclear factor RIP140) modulates transcriptional activation by steroid receptors such as NR3C1, NR3C2 and ESR1 []. It also modulates transcriptional repression by nuclear hormone receptors []and clock gene expression []. It consists of four distinct autonomous repression domains [].This domain is the first (N-terminal) repression domain of nuclear receptor-interacting protein 1 [, ].
Clock-interacting pacemaker or clock-interacting circadian protein (CIPC) is an additional negative-feedback regulator of the circadian clock, through inhibition of CLOCK-BMAL1 activity [, , ]. Studies in knockout mice suggest that it may not be critically required for basic clock function [].
ENOX proteins are growth-related cell surface proteins that catalyse both hydroquinone or NADH oxidation and protein disulfide-thiol interchange []. The two enzymatic activities oscillate with a period length of 24 minutes and play a role in control of the ultradian cellular biological clock [, ]. ENOX proteins may play roles in cancer, cellular time-keeping, growth, aging and neurodegenerative diseases [].
These proteins are found in a wide range of eukaryotes. They are nuclear proteins, suggested to play a role in the spliceosome complex []. XAP5 from Arabidopsis thaliana has been shown to be involved in light regulation of the circadian clock and photomorphogenesis [].
This entry represents a conserved domain found in a group of proteins called telomere-length regulation TEL2, or clock abnormal protein-2, which are conserved from plants to humans. These proteins regulate telomere length and contribute to silencing of sub-telomeric regions []. Tel2 acts at an early step of the TEL1/ATM pathway of DNA damage signaling []. In vitro the protein binds to telomeric DNA repeats.
This entry represents a group of plant WD repeat-containing proteins, including RUP1/2 (or EFO1/2) from Arabidopsis. EFO2 acts as a floral repressor, while EFO1 may not be directly involved in flowering, however, they have overlapping roles in regulating other developmental processes. Moreover, both EFO1/2 genes are regulated by the circadian clock [].
UBE3A (also known as E6-AP) is an E3 ubiquitin-protein ligase which accepts ubiquitin from an E2 ubiquitin-conjugating enzyme in the form of a thioester and transfers it to its substrates. It regulates cell proliferation by promoting proteasomal degradation of p27 []. It can also serve as a molecular circadian clock through regulating the BMAL1 transcription factor [].
Cold-regulated proteins 27 and 28 are regulated by low temperature and light. They are involved in central circadian clock regulation and in flowering promotion, by binding to the chromatin of clock-associated evening genes TOC1, PRR5, ELF4 and cold-responsive genes in order to repress their transcription [, ]. They are also involved in freezing tolerance regulation.
The melanoma antigen (MAGE) protein family contains more than 25 members that share a conserved MAGE homology domain (MHD). MAGED1 plays a role in anti-tumorigenesis in a variety of cell types and is involved in regulating circadian clock functions [, ]. It also plays important roles in the central nervous system in both developmental and adult stages [].
This entry represents a group of plant zinc finger proteins, including CONSTANS and related proteins. CONSTANS is a transcription factor that acts in the long day flowering pathway and may mediate between the circadian clock and the control of flowering [, ]. This entry also includes rice Ghd7 and CO3, which also control rice flowering [, ].
Nocturnin is a poly(A)-specific 3' exonuclease that specifically degrades the 3' poly(A) tail of RNA in a process known as deadenylation. Nocturnin is expressed in the cytoplasm of Xenopus laevis retinal photoreceptor cells in a rhythmic fashion, and it has been proposed that it participates in posttranscriptional regulation of the circadian clock or its outputs, and that the mRNA target(s) of this deadenylase are circadian clock-related []. In mouse, the nocturnin gene, mNoc, is expressed in a circadian pattern in a range of tissues including retina, spleen, heart, kidney, and liver. It is highly expressed in bone-marrow stromal cells, adipocytes and hepatocytes []. In mammals, nocturnin plays a role in regulating mesenchymal stem-cell lineage allocation, perhaps through regulating PPAR-gamma (peroxisome proliferator-activated receptor-gamma) nuclear translocation []. Nocturnin expression depends on the circadian clock and nutrient status. Loss of this activity results in increased metabolic flux and reduced obesity [].
The short CCT (CO, COL, TOC1) motif is found in a number of plant proteins, including Constans (CO), Constans-like (COL) and TOC1. The CCT motif is about 45 amino acids long and contains a putative nuclear localisation signal within the second half of the CCT motif []. The CCT motif is found in the Arabidopsis circadian rhythm protein TOC1, an autoregulatory response regulator homologue the controls the photoperiodic flowering through its clock function [].
Chromobox protein homologue 3 (CBX3, also known as HP1 gamma) is a component of heterochromatin that binds histone H3 tails methylated at 'Lys-9' which leads to epigenetic repression []. By interacting with MIS12 complex, it is involved in the formation of a functional kinetochore []. It recruits NIPBL to sites of DNA damage at double-strand breaks []. It is a component of the E2F6.com-1 []and PER []complexes. The PER complex controls the circadian clock [].
This entry represents the conserved RNA recognition motif (RRM) in ECTO-NOX proteins (ENOX). ENOX proteins are growth-related cell surface proteins that catalyse both hydroquinone or NADH oxidation and protein disulfide-thiol interchange []. The two enzymatic activities oscillate with a period length of 24 minutes and play a role in control of the ultradian cellular biological clock [, ]. ENOX proteins may play roles in cancer, cellular time-keeping, growth, aging and neurodegenerative diseases [].
This entry represents the C-terminal domain of the Nck-associated protein 5 (NCKAP5), also known as the Peripheral clock protein. NCKAP5 interacts with the SH3-containing region of the adaptor protein Nck. Nck is a protein that interacts with receptor tyrosine kinases and guanine nucleotide exchange factor Sos. The role of Nck can be thought of as similar to Grb2. The role of NCKAP5 is to assist Nck with its adaptor protein role [].
This entry represents a group of plant Myb domain proteins, including LUX, BOA and MYBC1 from Arabidopsis. LUX and BOA are transcription factors and critical components of the regulatory circuit of the circadian clock [, ]. LUX also binds toELF3 and associates with ELF4 in a diurnal complex which is required for the expression of the growth-promoting transcription factors PIF4 and PIF5 and subsequent hypocotyl growth in the early evening []. MYBC1 has been shown to negatively regulate freezing tolerance in Arabidopsis [].
HES-7 is a bHLH-type repressor that is both a direct target of the Notch signalling pathway, and part of a negative feedback mechanism required to attenuate Notch signalling [, ]. It can bind to its own promoter, thereby inhibiting its own transcription. In mouse its 3'UTR is essential for somite segmentation clock []. Mutations in the HES-7 gene cause spondylocostal dysostosis, an inherited disorder characterised by the presence of extensive hemivertebrae, truncal shortening and abnormally aligned ribs [].
This entry represents the repeats found in dinoflagellate luciferases.Luciferase is involved in catalysing the light emitting reaction in bioluminescence, and luciferin binding protein (LBP) is known to bind to luciferin (the substrate for luciferase) to stop it reacting with the enzyme and therefore switching off the bioluminescence function. The expression of these two proteins is controlled by a circadian clock at the translational level, with synthesis and degradation occurring on a daily basis [].
This entry represents the C-terminal region of the iron-sulphur protein LdpA (Light dependent period), which is found in phototropic organisms. LdpA was originally identified in cyanobacteria where it is involved in light-dependent modulation of the circadian clock. The presence of iron-sulphur clusters on LdpA suggests that it may modulate the circadian clock as an indirect function of light intensity by sensing changes in cellular physiology [].
The cryptochrome and photolyase families consist of structurally related flavin adenine dinucleotide (FAD) proteins that use the absorption of blue light to accomplish different tasks. The photolyasess use the blue light for light-driven electron transfer to repair UV-damaged DNA, while the cryptochromes are blue-light photoreceptors involved in the circadian clock for plants and animals [, ].This entry represents a branch of the photolyase/cryptochrome family that is known as the cryptochrome-DASH family (Cry-DASH). The Cry-DASH family members have been shown to act as photolyases with high degree of specificity for cyclobutane pyrimidine dimers in ssDNA [].
The cryptochrome and photolyase families consist of structurally related flavin adenine dinucleotide (FAD) proteins that use the absorption of blue light to accomplish different tasks. The photolyasess use the blue light for light-driven electron transfer to repair UV-damaged DNA, while the cryptochromes are blue-light photoreceptors involved in the circadian clock for plants and animals [, ].Members of this subfamily are from plants; they appear mostly to be regulatory proteins that respond to blue light. For instance, Arabidopsis cryptochromes Cry1 and Cry2 antagonistically regulate primary root elongation [, ]. Cry2 is also reported to interact with CIB1 and regulate transcription and floral initiation [].
This entry represents a conserved domain found in a group of proteins called telomere-length regulation TEL2, or clock abnormal protein-2, which are conserved from plants to humans. These proteins regulate telomere length and contribute to silencing of sub-telomeric regions []. In vitro the protein binds to telomeric DNA repeats. Tel2 acts at an early step of the TEL1/ATM pathway of DNA damage signaling []. The structure of Tel2 consists of HEAT-like helical repeats that assemble into two separate α-solenoids []. This entry represents the C-terminal solenoid which consists of eleven helices.
This entry represents a domain within bacterial and archaeal proteins, most of which are hypothetical. More than one copy is sometimes found in each protein in this entry. These include KaiC, which is one of the Kai proteins among which direct protein-protein association may be a critical process in the generation of circadian rhythms in cyanobacteria [].The circadian clock protein KaiC, is encoded in the kaiABC operon that controls circadian rhythms and may be universal inCyanobacteria. Each member contains two copies of this domain, which is alsofound in other proteins. KaiC performs autophosphorylation and acts as its own transcriptional repressor.
This domain is found in SRR1-like proteins.SRR1 are signalling proteins thought to be involved in regulating the circadian clock input pathway, which is required for normal oscillator function. In Arabidopsis thaliana it regulates the expression of clock-regulated genes such as CCA1 and TOC1. It is also involved in both the phytochrome B (PHYB) and PHYB-independent signaling pathways []. The mouse homologue of the plant circadian-regulating protein SRR1 plays roles in heme-regulated circadian rhythms and cell proliferation [].The yeast SRR1-like protein Ber1 is involved in microtubule stability [].
The prokineticin family includes prokinectin itself and related proteins such as BM8 and the AVIToxins. The suprachiasmatic nucleus (SCN) controls the circadian rhythm of physiological and behavioural processes in mammals. It has been shown that prokineticin 2 (PK2), a cysteine-rich secreted protein, functions as an output molecule from the SCN circadian clock. PK2 messenger RNA is rhythmically expressed in the SCN, and the phase of PK2 rhythm is responsive to light entrainment. Molecular and genetic studies have revealed that PK2 is a gene that is controlled by a circadian clock [].
This family consists of several plant specific light regulated Lir1 proteins. Lir1 mRNA accumulates in the light, reaching maximum and minimum steady-state levels at the end of the light and dark period, respectively. Plants germinated in the dark have very low levels of lir1 mRNA, whereas plants germinated in continuous light express lir1 at an intermediate but constant level. It is thought that lir1 expression is controlled by light and a circadian clock []. Lir1 interacts with LEAF-TYPE Ferredoxin-NADP(+) oxidoreductase (LFNR), an essential chloroplast enzyme functioning in the last step of photosynthetic linear electron transfer, and forms a thylakoid protein complex with LFNR, TIC62 and TROL [].
This entry represents a group of arginine N-methyltransferases, including Skb1 from S. pombe [], Hsl7 from S. cerevisiae []and their homologues PRMT5 from animals [, , ]and plants []. Skb1 is a mediator of hyperosmotic stress response in Schizosaccharomyces pombe []. Plant PMRT15 is involved in the post-transcriptional regulation of the circadian clock []. Human PRMT5 is a component of multiple protein complexes and contributes to essential cellular processes, such as RNA transport and splicing, cell cycle regulation, tumour growth, and chromatin remodelling, leading to either gene silencing or activation [].
This entry includes the plant Sensitivity To Red Light Reduced proteins (SRR1), yeast SRR1-like protein Ber1 and mammalian homologue SRR1 domain containing (SRRD) protein.SRR1 are signalling proteins thought to be involved in regulating the circadian clock input pathway, which is required for normal oscillator function. In Arabidopsis thaliana it regulates the expression of clock-regulated genes such as CCA1 and TOC1. It is also involved in both the phytochrome B (PHYB) and PHYB-independent signaling pathways []. The mouse homologue of the plant circadian-regulating protein SRR1 plays roles in heme-regulated circadian rhythms and cell proliferation [].The yeast SRR1-like protein Ber1 is involved in microtubule stability [].
In plants, a photoreceptor called phytochrome B (phyB) responds to red light and regulates the ability of plants to grow. PCH1 (At2g16365) regulates photoperiod-responsive growth by integrating the plant clock with light perception pathways. PCH1 stabilizes the structure of phyB so that it remains active, even in the dark. This prolonged activity acts as a molecular memory of prior exposure to light and helps to prevent plants from growing too much in the winter, when there are fewer hours of daylight. PCH1 is also found in other species of plants [].
This entry represents a domain found in arginine-N-methyltransferase PRMT5. Proteins containing this domain include Skb1 from S. pombe [], Hsl7 from S. cerevisiae []and their homologues PRMT5 from animals [, , ]and plants [].Skb1 is a mediator of hyperosmotic stress response in Schizosaccharomyces pombe []. Plant PMRT15 is involved in the post-transcriptional regulation of the circadian clock []. Human PRMT5 is a component of multiple protein complexes and contributes to essential cellular processes, such as RNA transport and splicing, cell cycle regulation, tumour growth, and chromatin remodelling, leading to either gene silencing or activation [].
This entry represents the N-terminal TIM barrel domain of PRMT5.Proteins containing this domain includes Skb1 from S. pombe [], Hsl7 from S. cerevisiae []and their homologues PRMT5 from animals [, , ]and plants []. Skb1 is a mediator of hyperosmotic stress response in Schizosaccharomyces pombe []. Plant PMRT15 is involved in the post-transcriptional regulation of the circadian clock []. Human PRMT5 is a component of multiple protein complexes and contributes to essential cellular processes, such as RNA transport and splicing, cell cycle regulation, tumour growth, and chromatin remodelling, leading to either gene silencing or activation [].
This entry represents the C-terminal oligomerisation domain of PRMT5.Proteins containing this domain includes Skb1 from S. pombe [], Hsl7 from S. cerevisiae []and their homologues PRMT5 from animals [, , ]and plants []. Skb1 is a mediator of hyperosmotic stress response in Schizosaccharomyces pombe []. Plant PMRT15 is involved in the post-transcriptional regulation of the circadian clock []. Human PRMT5 is a component of multiple protein complexes and contributes to essential cellular processes, such as RNA transport and splicing, cell cycle regulation, tumour growth, and chromatin remodelling, leading to either gene silencing or activation [].
This superfamily represents a structural domain consisting of four helices in a bundle with a right-handed superhelix. Homologous structural domains can be found in:The C-terminal domain of the circadian clock protein KaiAThe N-terminal domain of the phosphoserine phosphatase protein RsbUThe cyanobacterial clock proteins KaiA, KaiB and KaiC are proposed as regulators of the circadian rhythm in cyanobacteria. KaiA activates the expression of the kaiBC locus, while KaiC represses it. KaiA is composed of three functional domains: the N-terminal amplitude-amplifier domain, the central period-adjuster domain and the C-terminal clock-oscillator domain. The C-terminal domain is responsible for dimer formation, binding to KaiC, enhancing KaiC phosphorylation and generating the circadian oscillations []. The KaiA protein from Anabaena sp. (strain PCC 7120) lacks the N-terminal CheY-like domain.The phosphoserine phosphatase RsbU acts as a positive regulator of the general stress-response factor of Gram-positive organisms, sigma-B. RsbU dephosphorylates rsbV in response to environmental stress conveyed from the rsbXST module. The phosphatase activity of RsbU is stimulated during the stress response by associating with the RsbT kinase. This association leads to the induction of sigmaB activity. The N-terminal domain forms a helix-swapped dimer that is otherwise similar to the KaiA domain dimer. Deletions in the N-terminal domain are deleterious to the activity of RsbU. The C-terminal domain of RsbU is similar to the catalytic domains of PP2C-type phosphatases [].
The cyanobacterial clock proteins KaiA, KaiB and SasA are proposed as regulators of the circadian rhythm in cyanobacteria [, ]. Mutations in both proteins have been reported to alter or abolish circadian rhythmicity. KaiB adopts an α-β meander motif and is found to be a dimer []. KaiB was originally discovered from the cyanobacterium Synechococcus as part of the circadian clock gene cluster, kaiABC. KaiB attenuates KaiA-enhanced KaiC autokinase activity by interacting with KaiA-KaiC complexes in a circadian fashion [, ]. KaiB is membrane-associated as well as cytosolic. The amount of membrane-associated protein peaks in the evening (at circadian time (CT) 12-16) while the cytosolic form peaks later (at CT 20). The rhythmic localization of KaiB may function in regulating the formation of Kai complexes. SasA is a sensory histidine kinase which associates with KaiC []. Although it is not an essential oscillator component, it is important in enhancing kaiABC expression and is important in metabolic growth control under day/night cycle conditions. SasA contains an N-terminal sensory domain with a TRX fold which is involved in the SasA-KaiC interaction []. This domain shows high sequence similarity with KaiB []. However, the KaiB structure does not show a classical TRX fold. The N-terminal half of KaiB shares the same beta-α-β topology as TRX, but the topology of its C-terminal half diverges.
The cryptochrome and photolyase families consist of structurally related flavin adenine dinucleotide (FAD) proteins that use the absorption of blue light to accomplish different tasks. The photolyasess use the blue light for light-driven electron transfer to repair UV-damaged DNA, while the cryptochromes are blue-light photoreceptors involved in the circadian clock for plants and animals [, ]. On the basis of the primary structure, the cryptochrome/DNA photolyase family can be grouped into two classes []. The first class contains cryptochromes and DNA photolyases from eubacteria, archaea, fungi, animals and plants. The second class contains DNA photolyases from prokaryotes, plants and animals.This entry represents a number of conserved sequence regions found in the C-terminal region of the class 1 cryptochrome/DNA photolyase.
The cryptochrome and photolyase families consist of structurally related flavin adenine dinucleotide (FAD) proteins that use the absorption of blue light to accomplish different tasks. The photolyasess use the blue light for light-driven electron transfer to repair UV-damaged DNA, while the cryptochromes are blue-light photoreceptors involved in the circadian clock for plants and animals [, ]. On the basis of the primary structure, the cryptochrome/DNA photolyase family can be grouped into two classes []. The first class contains cryptochromes and DNA photolyases from eubacteria, archaea, fungi, animals and plants. The second class contains DNA photolyases from prokaryotes, plants and animals.This entry represents the class1 cryptochrome/DNA photolyase family. Its members include cryptochromes, DNA photolyases and cryptochrome-DASH (Cry-DASH). The Cry-DASH family members have been shown to act as photolyases with high degree of specificity for cyclobutane pyrimidine dimers in ssDNA [].
In Drosophila melanogaster (Fruit fly) the preprocorazonin consists of an 19 amino acid signal peptide, the 11 amino acid corazonin sequence followed by a 39 amino acid corazonin-precursor-related peptide (CPRP) and finally the 85 amino acid propeptide, [].Corazonin is a cardioactive peptide of insects, which is probably involved in the physiological regulation of the heart beat. Drosophila clock (clk) and cycle (cyc) proteins negatively regulate Crz transcription in a cell-specific manner []. Corazonin is expressed in neurosecretory neurons of the pars lateralis of the protocerebrum and transported via nervi corporis cardiaci to the storage lobes of the corpora cardiaca. The peptide occurs with a single isoform in all insects studied so far, with the exception of the Coleoptera in which none could be detected [].
This entry represents the C-terminal catalytic domain of the deadenylase nocturnin, and related domains. Nocturnin is a poly(A)-specific 3' exonuclease that specifically degrades the 3' poly(A) tail of RNA in a process known as deadenylation. This nuclease activity is manganese dependent. Nocturnin is expressed in the cytoplasm of Xenopus laevis retinal photoreceptor cells in a rhythmic fashion, and it has been proposed that it participates in posttranscriptional regulation of the circadian clock or its outputs, and that the mRNA target(s) of this deadenylase are circadian clock-related []. In mouse, the nocturnin gene, mNoc, is expressed in a circadian pattern in a range of tissues including retina, spleen, heart, kidney, and liver. It is highly expressed in bone-marrow stromal cells, adipocytes and hepatocytes []. In mammals, nocturnin plays a role in regulating mesenchymal stem-cell lineage allocation, perhaps through regulating PPAR-gamma (peroxisome proliferator-activated receptor-gamma) nuclear translocation [].
The cryptochrome and photolyase families consist of structurally related flavin adenine dinucleotide (FAD) proteins that use the absorption of blue light to accomplish different tasks. The photolyasess use the blue light for light-driven electron transfer to repair UV-damaged DNA, while the cryptochromes are blue-light photoreceptors involved in the circadian clock for plants and animals [, ]. On the basis of the primary structure, the cryptochrome/DNA photolyase family can be grouped into two classes []. The first class contains cryptochromes and DNA photolyases from eubacteria, archaea, fungi, animals and plants. The second class contains DNA photolyases from prokaryotes, plants and animals.This entry represents a number of conserved sequence regions found in the C-terminal region of the class 2 DNA photolyases.
Proteins in this entry belong to a family of dinoflagellate luciferase and luciferin binding proteins. Luciferase is involved in catalysing the light emitting reaction in bioluminescence and luciferin binding protein (LBP) is known to bind to luciferin (the substrate for luciferase) to stop it reacting with the enzyme and therefore switching off the bioluminescence function. The expression of these two proteins is controlled by a circadian clock at the translational level, with synthesis and degradation occurring on a daily basis [].This entry consists of a presumed N-terminal domain that is conserved between dinoflagellateluciferase and luciferin binding proteins. This domain is not, however, the catalytic part of the protein. It has been suggested that this region may mediate an interaction between LBP and Luciferase or their association with the vacuolar membrane [].
The prokineticin family includes prokinectin itself and related proteins such as BM8 and the AVIToxins. The suprachiasmatic nucleus (SCN) controls the circadian rhythm of physiological and behavioural processes in mammals. It has been shown that prokineticin 2 (PK2), a cysteine-rich secreted protein, functions as an output molecule from the SCN circadian clock. PK2 messenger RNA is rhythmically expressed in the SCN, and the phase of PK2 rhythm is responsive to light entrainment. Molecular and genetic studies have revealed that PK2 is a gene that is controlled by a circadian clock [].The prokinectin domain is found in the prokinectin family and the hainantoxins, where it comprises the whole length of the protein. This domain is also found at the C terminus of some members of the Dickkopf family.
The cryptochrome and photolyase families consist of structurally related flavin adenine dinucleotide (FAD) proteins that use the absorption of blue light to accomplish different tasks. The photolyasess use the blue light for light-driven electron transfer to repair UV-damaged DNA, while the cryptochromes are blue-light photoreceptors involved in the circadian clock for plants and animals [, ]. On the basis of the primary structure, the cryptochrome/DNA photolyase family can be grouped into two classes []. The first class contains cryptochromes and DNA photolyases from eubacteria, archaea, fungi, animals and plants. The second class contains DNA photolyases from prokaryotes, plants and animals.Similar to the distantly related microbial class I photolyases, class 2 enzymes repair UV-induced cyclobutane pyrimidine dimer (CPD) lesions within duplex DNA using blue/near-UV light []. There are a number of conserved sequence regions in all known class 2 DNA photolyases, especially in the C-terminal part. The structures of the class 2 DNA photolyase from archaea and rice have been solved [, ].
This entry represents a group of WD repeat-containing proteins, including DCAF7 from animals, LWD1/2/TTG1 from Arabidopsis and YPL247C from budding yeasts. In general, WD40 repeat domain-containing proteins are scaffolding elements for the assembly of multi-subunit protein complexes. DCAF7, also known as WDR68, interacts with Dual-specificity Tyrosine Phosphorylation-Regulated Kinase 1A (DYRK1A, a Down's syndrome-associated protein kinase) []and is required for Endothelin-1 (EDN1) signalling []. It also acts as a DDB1- and CUL4-associated factor []. Mutations in the DCAF7 gene have been linked to cleft lip with or without cleft palate (CL/P) []. In Arabidopsis, LWD1 and LWD2 serve as clock proteins involved in photoperiod flowering control []. TRANSPARENT TESTA GLABRA 1 (TTG1) is a regulator of early developmental traits and is also involved in flowering time regulation [].
This entry represents the DNA damage-binding protein 1 (DDB1) family, whose members are involved in DNA repair.The fission yeast members in this family includes Rik1 and Ddb1. Rik1 is a component of the Rik1-associated E3 ubiquitin ligase complex that shows ubiquitin ligase activity and is required for histone H3K9 methylation []. Ddb1 is a component of cullin 4A ubiquitin ligases, which regulates the selective proteolysis of key proteins in DNA repair, replication and transcription [, ].Mammalian Ddb1 is apart of the CUL4-DDB1 ubiquitin E3 ligase that regulates cell-cycle progression, replication and DNA damage response. The CUL4-DDB1 ubiquitin E3 ligase interacts with multiple WD40-repeat proteins and regulates histone methylation []. This complex also regulates the circadian clock function by mediating the ubiquitination and degradation of CRY1 [].The plant Ddb1 is part of the CUL4-DDB1-DDB2 E3 ligase involved in maintaining genome integrity upon UV stress [].
This entry represents the N-terminal domain of the Timeless protein. The timeless gene in Drosophila melanogasteris involved in circadian rhythm control []. Drosophila contains two paralogs, dTIM and dTIM2, acting in clock/photoreception and chromosome integrity/photoreception respectively. The mammalian TIMELESS (TIM) protein, originally identified based on its similarity to Drosophila dTIM, interacts with the clock proteins dCRY and dPER and is essential for circadian rhythm generation and photo-entrainment in the fly []. However, phylogenetic sequence analysis has demonstrated that dTIM2 is likely to be the orthologue of mammalian TIM and other widely conserved TIM-like proteins in eukaryotes []. These proteins include Saccharomyces cerevisiae Tof1, Schizosaccharomyces pombe Swi1, and Caenorhabditis elegans TIM. These proteins are not involved in the core clock mechanism, but instead play important roles in chromosome integrity, efficient cell growth and/or development [, ], with the exception of dTIM-2, that has an additional function in retinal photoreception [].Saccharomyces cerevisiae Tof1 is a subunit of a replication-pausing checkpoint complex (Tof1-Mrc1-Csm3) that acts at the stalled replication fork to promote sister chromatid cohesion after DNA damage, facilitating gap repair of damaged DNA [, ]. Schizosaccharomyces pombe Swi1 and Swi3 form the fork protection complex that coordinates leading- and lagging-strand synthesis and stabilizes stalled replication forks []. In humans timeless forms a stable complex with its partner protein Tipin. The Timeless-Tipin complex has been reported to travel along with the replication fork during unperturbed DNA replication. Moreover, the Timeless-Tipin-Claspin complex contributes to full activation of the ATR-Chk1 signaling pathway through the recruitment of Chk1 to arrested replication forks for sufficient ATR-mediated phosphorylation. It also interacts with PARP-1, and this interaction is required for efficient homologous recombination repair [].
This entry represents the C-terminal domain found in the Timeless (TIM) proteins. This domain can be found in TIM homologues mostly from animals. This domain found in hTIM has been shown to bind to the PARP-1 catalytic domain [].The timeless gene in Drosophila melanogasteris involved in circadian rhythm control []. Drosophila contains two paralogs, dTIM and dTIM2, acting in clock/photoreception and chromosome integrity/photoreception respectively. The mammalian TIMELESS (TIM) protein, originally identified based on its similarity to Drosophila dTIM, interacts with the clock proteins dCRY and dPER and is essential for circadian rhythm generation and photo-entrainment in the fly []. However, phylogenetic sequence analysis has demonstrated that dTIM2 is likely to be the orthologue of mammalian TIM and other widely conserved TIM-like proteins in eukaryotes []. These proteins include Saccharomyces cerevisiae Tof1, Schizosaccharomyces pombe Swi1, and Caenorhabditis elegans TIM. These proteins are not involved in the core clock mechanism, but instead play important roles in chromosome integrity, efficient cell growth and/or development [, ], with the exception of dTIM-2, that has an additional function in retinal photoreception [].Saccharomyces cerevisiae Tof1 is a subunit of a replication-pausing checkpoint complex (Tof1-Mrc1-Csm3) that acts at the stalled replication fork to promote sister chromatid cohesion after DNA damage, facilitating gap repair of damaged DNA [, ]. Schizosaccharomyces pombe Swi1 and Swi3 form the fork protection complex that coordinates leading- and lagging-strand synthesis and stabilizes stalled replication forks []. In humans timeless forms a stable complex with its partner protein Tipin. The Timeless-Tipin complex has been reported to travel along with the replication fork during unperturbed DNA replication. Moreover, the Timeless-Tipin-Claspin complex contributes to full activation of the ATR-Chk1 signaling pathway through the recruitment of Chk1 to arrested replication forks for sufficient ATR-mediated phosphorylation. It also interacts with PARP-1, and this interaction is required for efficient homologous recombination repair [].
The timeless gene in Drosophila melanogasteris involved in circadian rhythm control []. Drosophila contains two paralogs, dTIM and dTIM2, acting in clock/photoreception and chromosome integrity/photoreception respectively. The mammalian TIMELESS (TIM) protein, originally identified based on its similarity to Drosophila dTIM, interacts with the clock proteins dCRY and dPER and is essential for circadian rhythm generation and photo-entrainment in the fly []. However, phylogenetic sequence analysis has demonstrated that dTIM2 is likely to be the orthologue of mammalian TIM and other widely conserved TIM-like proteins in eukaryotes []. These proteins include Saccharomyces cerevisiae Tof1, Schizosaccharomyces pombe Swi1, and Caenorhabditis elegans TIM. These proteins are not involved in the core clock mechanism, but instead play important roles in chromosome integrity, efficient cell growth and/or development [, ], with the exception of dTIM-2, that has an additional function in retinal photoreception [].Saccharomyces cerevisiae Tof1 is a subunit of a replication-pausing checkpoint complex (Tof1-Mrc1-Csm3) that acts at the stalled replication fork to promote sister chromatid cohesion after DNA damage, facilitating gap repair of damaged DNA [, ]. Schizosaccharomyces pombe Swi1 and Swi3 form the fork protection complex that coordinates leading- and lagging-strand synthesis and stabilizes stalled replication forks []. In humans timeless forms a stable complex with its partner protein Tipin. The Timeless-Tipin complex has been reported to travel along with the replication fork during unperturbed DNA replication. Moreover, the Timeless-Tipin-Claspin complex contributes to full activation of the ATR-Chk1 signaling pathway through the recruitment of Chk1 to arrested replication forks for sufficient ATR-mediated phosphorylation. It also interacts with PARP-1, and this interaction is required for efficient homologous recombination repair [].
This entry describes a narrow clade of cyanobacterial deoxyribodipyrimidine photolyase (or DNA photolyase). This group, in contrast to several closely related proteins, uses a chromophore that, in other lineages is modified further to become coenzyme F420. This chromophore is called 8-HDF in most articles on the DNA photolyase and FO in most literature on coenzyme F420. This entry includes PhrA from Synechocystis sp. strain PCC 6803. PhrA is a DNA photolyase responsible for the majority of the observed UV resistance in Synechocystis 6803 [, ]. The cryptochrome and photolyase families consist of structurally related flavin adenine dinucleotide (FAD) proteins that use the absorption of blue light to accomplish different tasks. The photolyasess use the blue light for light-driven electron transfer to repair UV-damaged DNA, while the cryptochromes are blue-light photoreceptors involved in the circadian clock for plants and animals [, ]. On the basis of the primary structure, the cryptochrome/DNA photolyase family can be grouped into two classes []. The first class contains cryptochromes and DNA photolyases from eubacteria, archaea, fungi, animals and plants. The second class contains DNA photolyases from prokaryotes, plants and animals.
Haems are metalloporphyrins that serve as prosthetic groups for a variety of biological processes, including respiration, gas sensing, xenobiotic detoxification, cell differentiation, circadian clock control, metabolic reprogramming and microRNA processing. Haem is usually synthesised by a multistep biosynthetic pathway. The cellular pathways and molecules that mediate intracellular haem trafficking are still largely unknown [].Caenorhabditis elegans and related helminths are natural haem auxotrophs that acquire environmental haem for incorporation into haemoproteins. In C.elegans, it has been shown that HRG-1 proteins are essential for haem homeostasis. In worms, depletion of hrg-1, or its paralogue hrg-4, results in the disruption of organismal haem sensing, and an abnormal response to haem analogues [].HRG-1 and HRG-4 are transmembrane (TM) proteins that reside in distinct intracellular compartments. Transient knockdown of hrg-1 in zebrafish leads to hydrocephalus, yolk tube malformations and profound defects in erythropoiesis-phenotypes that are fully rescued by worm HRG-1. Human and worm proteins have been shown to co-localise, and bind and transport haem, thus establishing an evolutionarily conserved function for HRG-1 [].Sequence analysis of HRG-1 has identified 4 predicted TM domains, and a conserved tyrosine and acidic-di-leucine-based sorting signal in the cytoplasmic C terminus. In addition, residues that could potentially either directly bind haem (H90 in TM2) or interact with the haem side chains (FARKY) are situated in the C-terminal tail [].
This entry represents a multi-helical domain, composed of two alpha subdomains, found in the C terminus of the cryptochrome proteins and DNA photolyases. It acts as a FAD-binding domain [].The cryptochrome and photolyase families consist of structurally related flavin adenine dinucleotide (FAD) proteins that use the absorption of blue light to accomplish different tasks. The photolyasess use the blue light for light-driven electron transfer to repair UV-damaged DNA, while the cryptochromes are blue-light photoreceptors involved in the circadian clock for plants and animals [, ]. DNA photolyases are DNA repair enzymes that repair mismatched pyrimidine dimers induced by exposure to ultra-violet light. They bind to UV-damaged DNA containing pyrimidine dimers and, upon absorbing a near-UV photon (300 to 500 nm), they catalyse dimer splitting, breaking the cyclobutane ring joining the two pyrimidines of the dimer so as to split them into the constituent monomers; this process is called photoreactivation. DNA photolyases require two choromophore-cofactors for their activity. All monomers contain a reduced FAD moiety, and, in addition, either a reduced pterin or 8-hydroxy-5-diazaflavin as a second chromophore. Either chromophore may act as the primary photon acceptor, peak absorptions occurring in the blue region of the spectrum and in the UV-B region, at a wavelength around 290nm [, ].
The PAS (Per, Arnt, Sim) domain [, ]is an approximately 300 amino-acid segment of sequence similarity which is conserved between the Drosophila protein period clock (PER), the Ah receptor nuclear translocator (ARNT) and the Drosophila single-minded (SIM). It is composed of two or more imperfect repeats (PAS-1, PAS-2). In addition, some proteins have another similar region of 40-45 amino acids situated carboxy-terminal to any PAS repeat and which contributes to the PAS structural domain: the PAC motif. The PAS family can be divided in two groups; the proteins that have the PAS motif followed by a PAC motif, and those that do not. It appears that these domains are directly linked, and that together they form the conserved 3D PAS fold. The division between the PAS and PAC domains is caused by major differences in sequences in the region connecting these two motifs []. Within the bHLH/PAS proteins, the PAS domain is involved in protein dimerization with another protein of the family. It has also been associated with light reception, light regulation and circadian rhythm regulators (clock).In bacteria, the PAS domain is usually associated with the input domain of a histidine kinase, or a sensor protein that regulates a histidine kinase.
This entry represents a multi-helical domain found in the C terminus of the cryptochrome proteins and DNA photolyases. It acts as a FAD-binding domain [].The cryptochrome and photolyase families consist of structurally related flavin adenine dinucleotide (FAD) proteins that use the absorption of blue light to accomplish different tasks. The photolyasess use the blue light for light-driven electron transfer to repair UV-damaged DNA, while the cryptochromes are blue-light photoreceptors involved in the circadian clock for plants and animals [, ]. DNA photolyases are DNA repair enzymes that repair mismatched pyrimidine dimers induced by exposure to ultra-violet light. They bind to UV-damaged DNA containing pyrimidine dimers and, upon absorbing a near-UV photon (300 to 500 nm), they catalyse dimer splitting, breaking the cyclobutane ring joining the two pyrimidines of the dimer so as to split them into the constituent monomers; this process is called photoreactivation. DNA photolyases require two choromophore-cofactors for their activity. All monomers contain a reduced FAD moiety, and, in addition, either a reduced pterin or 8-hydroxy-5-diazaflavin as a second chromophore. Either chromophore may act as the primary photon acceptor, peak absorptions occurring in the blue region of the spectrum and in the UV-B region, at a wavelength around 290nm [, ].
This is a family of eukaryotic proteins found in animals, plants, and yeasts that includes Atg7p (YHR171W) from Saccharomyces cerevisiae (Baker's yeast) and ATG7 from Pichia angusta. Members are about 650 to 700 residues in length and include a central domain of about 150 residues shared with the ThiF/MoeB/HesA family of proteins. A low level of similarity toubiquitin-activating enzyme E1 is described in a paper on peroxisome autophagy mediated by ATG7 [], and is the basis of the name ubiquitin activating enzyme E1-like protein. Members of the family are involved in protein lipidation events analogous to ubiquitination and required for membrane fusion events during autophagy.This protein is important for several processes. It plays a key role in the maintenance of axonal homeostasis, the prevention of axonal degeneration [], the maintenance of hematopoietic stem cells [], the formation of Paneth cell granules [[cite22291845]], as well as in adipose differentiation []. It is involved in circadian clock regulation in the liver and glucose metabolism through the autophagic degradation of CRY1 (clock repressor) in a time-dependent manner [].
CheY is a member of the response regulator family in bacterial two-component signalling systems, where CheY receives the signal from the sensor partner, usually a histidine protein kinase. Signal transduction involves phosphotransfer, whereby the histidine kinase phosphorylates a conserved aspartate in the response regulator to activate responses to environmental signals []. CheY is a single domain protein that folds into a compact globular unit with a flavodoxin-like fold consisting of three-layer alpha/beta/alpha sandwich with 21345 beta topology, where the phosphorylation region lies in a cavity.Other members of the response regulator family contain a CheY-like receiver domain, which is often found N-terminal to a DNA-binding effector domain. Examples include NarL (nitrate/nitrite response regulator), NtrC (nitrogen regulatory protein C), Spo0A and Spo0F (sporulation response) from Bacillus, PhoA and PhoB cyclin-dependent kinases from Aspergillus, among others.AmiR, the positive regulator of the amidase operon in Psuedomonas, is an unusual member of the bacterial response regulator family; AmiR is able to bind RNA and uses ligand-regulated activation rather than phopho-activation. It has a CheY-like fold at its N terminus, but contains two subdomains in a C-terminal extension, one forming a coiled-coil and the other a long alpha helix. As such AmiR may represent a new family of RNA-binding response regulators [].CheY-like domains can be found in other protein families as well. Examples include the receiver domain of the ethylene receptor (ETR1) from Arabidopsis, which is involved in ethylene detection and signal transduction []; the N-terminal wing' domain of ornithine decarboxylase from Lactobacilli, which catalyses the conversion of ornithine to putrescine at the beginning of the polyamine pathway []. The N-terminal domain of the circadian clock protein, KaiA, from cyanobacteria, acts as a psuedo-receiver domain, but lacks the conserved aspartyl residue required for phosphotransfer in response regulators [].
G protein-coupled receptors (GPCRs) constitute a vast protein family that encompasses a wide range of functions, including various autocrine, paracrine and endocrine processes. They show considerable diversity at the sequence level, on the basis of which they can be separated into distinct groups []. The term clan can be used to describe the GPCRs, as they embrace a group of families for which there are indications of evolutionary relationship, but between which there is no statistically significant similarity in sequence []. The currently known clan members include rhodopsin-like GPCRs (Class A, GPCRA), secretin-like GPCRs (Class B, GPCRB), metabotropic glutamate receptor family (Class C, GPCRC), fungal mating pheromone receptors (Class D, GPCRD), cAMP receptors (Class E, GPCRE) and frizzled/smoothened (Class F, GPCRF) [, , , , ]. GPCRs are major drug targets, and are consequently the subject of considerable research interest. It has been reported that the repertoire of GPCRs for endogenous ligands consists of approximately 400 receptors in humans and mice []. Most GPCRs are identified on the basis of their DNA sequences, rather than the ligand they bind, those that are unmatched to known natural ligands are designated by as orphan GPCRs, or unclassified GPCRs [].The rhodopsin-like GPCRs (GPCRA) represent a widespread protein family that includes hormone, neurotransmitter and light receptors, all of which transduce extracellular signals through interaction with guanine nucleotide-binding (G) proteins. Although their activating ligands vary widely in structure and character, the amino acid sequences of the receptors are very similar and are believed to adopt a common structural framework comprising 7 transmembrane (TM) helices [, , ].Adrenocorticotrophin (ACTH), melanocyte-stimulating hormones (MSH) andbeta-endorphin are peptide products of pituitary pro-opiomelanocortin.ACTH regulates synthesis and release of glucocorticoids and aldosteronein the adrenal cortex; it also has a trophic action on these cells.ACTH and beta-endorphin are synthesised and released in response tocorticotrophin-releasing factor at times of stress (heat, cold, infections,etc.) - their release leads to increased metabolism and analgesia.MSH has a trophic action on melanocytes, and regulates pigment productionin fish and amphibia. The ACTH receptor is found in high levels inthe adrenal cortex - binding sites are present in lower levels in theCNS. The MSH receptor is expressed in high levels in melanocytes,melanomas and their derived cell lines. Receptors are found in lowlevels in the CNS. MSH regulates temperature control in the septal regionof the brain and releases prolactin from the pituitary.This entry represents Melanocortin receptor 3-5 (MC3-5R) from chordates. These protein are receptors for MSH (alpha, beta and gamma) and ACTH. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. MC3R is required for expression of anticipatory patterns of activity and wakefulness during periods of limited nutrient availability and for the normal regulation of circadian clock activity in the brain []. MC4R plays a central role in energy homeostasis and somatic growth [, , ]. MC5R is a possible mediator of the immunomodulation properties of melanocortins, playing a role in immune reaction and inflammatory response as well as in the regulation of sexual behaviour, thermoregulation, and exocrine secretion [].
