This is a superfamily of proteins found in severe acute respiratory syndrome coronavirus (SARS-CoV), and SARS-like viruses. Protein 9b is also known as ORF-9b and accessory protein 9b. The protein has a novel fold which forms a dimeric tent-like beta structure with an amphipathic surface, and a central hydrophobic cavity that binds lipid molecules [
]. This cavity is likely to be involved in membrane attachment []. SARS-CoV ORF-9b targets mitochondrial antiviral signalling proteins (MAVS), suppressing innate immunity [,
,
].
Wings apart-like protein (WAPL) regulates heterochromatin structure [
]. It is required to hold sister chromatids of meiotic heterochromatin together and is implicated in both heterochromatin pairing during female meiosis and the modulation of position-effect variegation (PEV) []. hWAPL (), the human homologue, is found to play a role in the development of cervical carcinogenesis, and is thought to have similar functions to Drosophila wapl protein [
]. Malfunction of the hWAPL pathway is thought to activate an apoptotic pathway that consequently leads to cell death [].
This entry includes TMEM131 and TMEM131L. In humans, TMEM131L may regulate immature single-positive thymocyte proliferation arrest by acting through mixed Wnt-dependent and -independent mechanisms [
].
The small heat shock proteins of vertebrates are thought to play a major role in the cellular response to stress, and appear to play a role in a range of other physiological activities. Indeed, in response to many forms of stress, including heat, the expression of heat shock proteins is increased, and coincidentally these cells become more stress-resistant. One of these proteins is Heat Shock Protein (hsp) 27, for which 3 hypotheses currently exist to explain its mechanism of action: (i) it has chaperone-like activity, serving as a site where denatured, unfolding proteins can bind until hsp70-dependent refolding can occur; (ii) it stabilises microfilaments, strengthening the cytoskeleton; and (iii) it enhances levels of the cellular antioxidant glutathione [
]. It was hypothesised that hsp27 associates with different protein partners in order to effect its various cellular functions. Thus, a yeast two-hybrid screen was performed on a rat Sertoli cell cDNA library, which identified a novel binding protein, termed HSPB1-associated protein 1 or Protein Associated with Small Stress protein 1.
The structure of Sulfolobus spindle-shaped virus 1 (SSV1) protein D-63 reveals a helix-turn-helix motif that dimerises to form an antiparallel four-helix bundle. Its structure suggests that it may function as an adaptor protein in macromolecular assembly [
].
The fliD operon of several bacteria consists of three flagellar genes, fliD, fliS, and fliT, and is transcribed in this order [
]. In Bacillus subtilis the operon encoding the flagellar proteins FliD, FliS, and FliT is sigma D-dependent [].FliS is a flagellin-specific T3S chaperone that binds in 1:1 stoichiometry to the C-terminal region of flagellin and facilitates its export, preventing polymerization in the cytoplasm [
,
,
]. The fliS gene is necessary for flagellation. In Aeromonas, deletion of this gene (called flaJ) resulted in the complete loss of motility, flagellin expression, and adherence [].
Nta1 is an amidase that removes the amide group from N-terminal asparagine and glutamine residues to generate proteins with N-terminal aspartate and glutamate residues that are targets of ubiquitin-mediated degradation [
].
Hematopoietic lineage cell-specific protein-1 (HS1) binding protein 3 (HS1BP3) associates with HS1 proteins through their SH3 domains, suggesting a role in mediating signaling. It has been reported that HS1BP3 might affect the IL-2 signaling pathway in hematopoietic lineage cells [
]. Mutations in HS1BP3 may also be associated with familial Parkinson disease and essential tremor [,
]. HS1BP3 contains a PX domain, a leucine zipper, motifs similar to immunoreceptor tyrosine-based inhibitory motif and proline-rich regions [
].
This entry represents a group of RING-finger proteins, including Mag2 from budding yeasts and Rnf10 from animals. Rnf10 has been shown to be involved in transcriptional regulation of the myelin-associated glycoprotein gene and myelin formation in Schwann cells [
].
Calcineurin is a Ser/Thr-specific calcium and calmodulin-dependent protein phosphatase that plays an essential role in the T cell activation pathway. Calcineurin and Nuclear factor of Activated T-cell (NFAT) proteins have been shown to participate in signalling cascades that govern the development and function of the immune, nervous, cardiovascular and musculoskeletal systems [
]. Calcineurin is a heterodimeric protein consisting of: i) a catalytic subunit calcineurin A, which contains an active site dinuclear metal centre, and ii) a tightly associated, myristoylated, Ca(2+)-binding subunit, calcineurin B [].
This entry includes Rfx1 from budding yeasts, Sak1 from fission yeasts and RFX1-8 from humans [
]. They are transcription factors that contain a RFX DNA binding domain and a conserved C-terminal region [].Mutations in the RFX5 gene cause Bare lymphocyte syndrome 2 (BLS2), a severe combined immunodeficiency disease with early onset [
]. Mutations in the RFX6 gene cause Mitchell-Riley syndrome (MTCHRS), a disorder characterized by neonatal diabetes, hypoplastic or annular pancreas, duodenal and jejunal atresia, and absent gallbladder [,
].
This entry contains proteins with a C-terminal MOFRL (multi-organism fragment with rich Leucine) domain. Proteins with this domain frequently possess an N-terminal MOFRL-associated domain. The functions of these domains are not known. Proteins with these domains include:
Glycerate kinase (GLYCTK; EC 2.7.1.31), which phosphorylates D-glycerate to generate 3-phospho-D-glycerate. D-glyceric aciduria, which can lead to mental retardation or microcephaly, results from mutations in the GLYCTK gene [
,
].Glycerate 2-kinase (GCK; EC 2.7.1.165), with a similar function but generates 2-phospho-D-glycerate, is found in archaea [
] and the thermophilic bacterium Thermotoga maritima[
].Uncharacterized protein C13B9.2 from the nematode
Caenorhabditis elegans.
RALBP1, also known as RLIP76, is a Ral-binding GTPase activating protein implicated in a number of cell processes, including receptor-mediated endocytosis, cell migration, mitochondrial division and metabolite transport [
]. It transports glutathione-conjugates of electrophilic compounds and may contribute to the multidrug resistance []. It has been shown to mediate ATP-dependent transport of glutathione-conjugates and doxorubicin in human erythrocytes [].
This family includes the
TRL protein that is found in a locus that includes several tRNAs. The function of this protein is not known [
]. The proteins in this family usually have a lipoprotein attachment site at their N terminus.
The eukaryotic like-Sm (LSm) proteins assemble into a hetero-heptameric rings (LSm2-8 or LSm1-7) around a wide spectrum of RNAs. The LSm2-8 ring functions during general RNA maturation in the nucleus, while the LSm1-7 ring functions during mRNA degradation in the cytoplasm [
,
]. LSm2-8 form the core of the U6 snRNP particle that, in turn, assembles with other components to form the spliceosome which is responsible for the excision of introns and the ligation of exons [,
]. The LSm1-7 ring is involved in recognition of the 3' uridylation tag and recruitment of the decapping machinery [,
].Members of the LSm family share a highly conserved Sm fold containing an N-terminal helix followed by a strongly bent five-stranded antiparallel β-sheet [
].This entry represents LSm5.
Pre-rRNA-processing protein Esf1 is required for the biogenesis of 18S rRNA in Saccharomyces cerevisiae. It has a role in early pre-rRNA processing because it associates with U3 and U14 snoRNAs but not the SSU processome [
]. Homologues are found in other fungi, animals and plants.
Proteins in this entry contain an N-terminal F-box and a C-terminal F-box associated (FBA) domain. The F-box is a conserved domain that is present in numerous proteins with a bipartite structure [
]. Through the F-box, these proteins are linked to the Skp1 protein and the core of SCFs (Skp1-cullin-F-box protein ligase) complexes. SCFs complexes constitute a new class of E3 ligases []. They function in combination with the E2 enzyme Cdc34 to ubiquitinate G1 cyclins, Cdk inhibitors and many other proteins, to mark them for degradation. The binding of the specific substrates by SCFs complexes is mediated by divergent protein-protein interaction motifs present in F-box proteins, like WD40 repeats, leucine rich repeats [,
] or ANK repeats.
This entry contains a protein of unknown function, the hypothetical protein HI1480 from Haemophilus influenzae. Its structure has been determined (
) and consists of a beta-alpha(4)-beta-α-β fold with segregated α-helical and β-sheet subdomains and a dimeric β-sheet barrel, the helical region contains a four-helix bundle [
].
The CRISPR-Cas system is a prokaryotic defense mechanism against foreign genetic elements. The key elements of this defense system are the Cas proteins and the CRISPR RNA. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are a family of DNA direct repeats separated by regularly sized non-repetitive spacer sequences that are found in most bacterial and archaeal genomes [
]. CRISPRs appear to provide acquired resistance against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain sequences complementary to antecedent mobile elements and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA).The defense reaction is divided into three stages. In the adaptation stage, the invader DNA is cleaved, and a piece of it is selected to be integrated as a new spacer into the CRISPR locus, where it is stored as an identity tag for future attacks by this invader. During the second stage (the expression stage), the CRISPR RNA (pre-crRNA) is transcribed and subsequently processed into the mature crRNAs. In the third stage (the interference stage), Cas proteins, together with crRNAs, identify and degrade the invader [
,
,
].The CRISPR-Cas systems have been sorted into three major classes. In CRISPR-Cas types I and III, the mature crRNA is generally generated by a member of the Cas6 protein family. Whereas in system III the Cas6 protein acts alone, in some class I systems it is part of a complex of Cas proteins known as Cascade (CRISPR-associated complex for antiviral defense). The Cas6 protein is an endoribonuclease necessary for crRNA production whereas the additional Cas proteins that form the Cascade complex are needed for crRNA stability [
]. This entry is found in CRISPR-associated (cas) proteins in the genomes of Geobacter sulfurreducens PCA and Desulfotalea psychrophila LSv54 (both Desulfobacterales from the Deltaproteobacteria), Gemmata obscuriglobus (a Planctomycete), and Actinomyces naeslundii MG1 (Actinobacteria).
The CRISPR-Cas system is a prokaryotic defense mechanism against foreign genetic elements. The key elements of this defense system are the Cas proteins and the CRISPR RNA. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are a family of DNA direct repeats separated by regularly sized non-repetitive spacer sequences that are found in most bacterial and archaeal genomes [
]. CRISPRs appear to provide acquired resistance against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain sequences complementary to antecedent mobile elements and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA).The defense reaction is divided into three stages. In the adaptation stage, the invader DNA is cleaved, and a piece of it is selected to be integrated as a new spacer into the CRISPR locus, where it is stored as an identity tag for future attacks by this invader. During the second stage (the expression stage), the CRISPR RNA (pre-crRNA) is transcribed and subsequently processed into the mature crRNAs. In the third stage (the interference stage), Cas proteins, together with crRNAs, identify and degrade the invader [
,
,
].The CRISPR-Cas systems have been sorted into three major classes. In CRISPR-Cas types I and III, the mature crRNA is generally generated by a member of the Cas6 protein family. Whereas in system III the Cas6 protein acts alone, in some class I systems it is part of a complex of Cas proteins known as Cascade (CRISPR-associated complex for antiviral defense). The Cas6 protein is an endoribonuclease necessary for crRNA production whereas the additional Cas proteins that form the Cascade complex are needed for crRNA stability [
]. This entry represents tha Csx3 family of Cas proteins, which is encoded in CRISPR-associated gene cluster near CRISPR repeats in the genomes of several different thermophiles: Archaeoglobus fulgidus (archaeal), Aquifex aeolicus (Aquificae), Dictyoglomus thermophilum (Dictyoglomi), and a thermophilic Synechococcus (Cyanobacteria). It is not yet assigned to a specific CRISPR/cas subtype (hence the x designation csx3).
The CRISPR-Cas system is a prokaryotic defense mechanism against foreign genetic elements. The key elements of this defense system are the Cas proteins and the CRISPR RNA. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are a family of DNA direct repeats separated by regularly sized non-repetitive spacer sequences that are found in most bacterial and archaeal genomes [
]. CRISPRs appear to provide acquired resistance against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain sequences complementary to antecedent mobile elements and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA).The defense reaction is divided into three stages. In the adaptation stage, the invader DNA is cleaved, and a piece of it is selected to be integrated as a new spacer into the CRISPR locus, where it is stored as an identity tag for future attacks by this invader. During the second stage (the expression stage), the CRISPR RNA (pre-crRNA) is transcribed and subsequently processed into the mature crRNAs. In the third stage (the interference stage), Cas proteins, together with crRNAs, identify and degrade the invader [
,
,
].The CRISPR-Cas systems have been sorted into three major classes. In CRISPR-Cas types I and III, the mature crRNA is generally generated by a member of the Cas6 protein family. Whereas in system III the Cas6 protein acts alone, in some class I systems it is part of a complex of Cas proteins known as Cascade (CRISPR-associated complex for antiviral defense). The Cas6 protein is an endoribonuclease necessary for crRNA production whereas the additional Cas proteins that form the Cascade complex are needed for crRNA stability [
]. This entry is encoded within the CRISPR-associated RAMP module, a set of six genes found together in prokaryotic genomes [
]. This gene cluster is found only in species with CRISPR repeats, usually near the repeats themselves. Because most of the six genes (but not those encoding this entry) contain RAMP domains, and because its appearance in a genome appears to depend on other CRISPR-associated Cas genes, the set is designated the CRISPR RAMP module. This entry, typified by TM1794 from Thermotoga maritima, is designated Cmr2.
This family of proteins is involved in sporulation. In Bacillus subtilis its expression is regulated by the early mother-cell-specific transcription factor sigma-E [
].
This entry represents the Csm6 family of Cas proteins [
]. CRISPR (clustered regularly interspaced short palindromic repeat) is an adaptive immune system that provides protection against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain spacers, sequences complementary to antecedent mobile elements, and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA) [].
The CRISPR-Cas system is a prokaryotic defense mechanism against foreign genetic elements. The key elements of this defense system are the Cas proteins and the CRISPR RNA. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are a family of DNA direct repeats separated by regularly sized non-repetitive spacer sequences that are found in most bacterial and archaeal genomes [
]. CRISPRs appear to provide acquired resistance against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain sequences complementary to antecedent mobile elements and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA).The defense reaction is divided into three stages. In the adaptation stage, the invader DNA is cleaved, and a piece of it is selected to be integrated as a new spacer into the CRISPR locus, where it is stored as an identity tag for future attacks by this invader. During the second stage (the expression stage), the CRISPR RNA (pre-crRNA) is transcribed and subsequently processed into the mature crRNAs. In the third stage (the interference stage), Cas proteins, together with crRNAs, identify and degrade the invader [
,
,
].The CRISPR-Cas systems have been sorted into three major classes. In CRISPR-Cas types I and III, the mature crRNA is generally generated by a member of the Cas6 protein family. Whereas in system III the Cas6 protein acts alone, in some class I systems it is part of a complex of Cas proteins known as Cascade (CRISPR-associated complex for antiviral defense). The Cas6 protein is an endoribonuclease necessary for crRNA production whereas the additional Cas proteins that form the Cascade complex are needed for crRNA stability [
]. This entry represents the Cxs9 family of Cas proteins found in archaea. These proteins are encoded in the midst of a cas gene operon [
].
The CRISPR-Cas system is a prokaryotic defense mechanism against foreign genetic elements. The key elements of this defense system are the Cas proteins and the CRISPR RNA. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are a family of DNA direct repeats separated by regularly sized non-repetitive spacer sequences that are found in most bacterial and archaeal genomes [
]. CRISPRs appear to provide acquired resistance against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain sequences complementary to antecedent mobile elements and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA).The defense reaction is divided into three stages. In the adaptation stage, the invader DNA is cleaved, and a piece of it is selected to be integrated as a new spacer into the CRISPR locus, where it is stored as an identity tag for future attacks by this invader. During the second stage (the expression stage), the CRISPR RNA (pre-crRNA) is transcribed and subsequently processed into the mature crRNAs. In the third stage (the interference stage), Cas proteins, together with crRNAs, identify and degrade the invader [
,
,
].The CRISPR-Cas systems have been sorted into three major classes. In CRISPR-Cas types I and III, the mature crRNA is generally generated by a member of the Cas6 protein family. Whereas in system III the Cas6 protein acts alone, in some class I systems it is part of a complex of Cas proteins known as Cascade (CRISPR-associated complex for antiviral defense). The Cas6 protein is an endoribonuclease necessary for crRNA production whereas the additional Cas proteins that form the Cascade complex are needed for crRNA stability [
]. This entry represents the Cxs8 family of Cas proteins, whose funciton is unknown. These proteins are encoded in the midst of a cas gene operon [
].
Chlorosomes, which are attached to the inner surface of the cytoplasmic membrane, consist of four polypeptides and associated pigments and lipids. The principal light-harvesting pigment of the green filamentous bacterium Chloroflexus aurantiacus is bacteriochlorophyll (Bchl) c. This pigment is either bound to, or constrained by, a small approximately 80-residue polypeptide designated Bchlc-binding protein. In C. aurantiacus, a C-terminal extension is believed to play a role in proper incorporation of the protein during chlorosome assembly [
]. The protein has a high degree of similarity to Bchlc-binding proteins of other photosynthetic bacteria.
This family includes Wadjet protein JetB, a component of anti plasmid transformation system Wadjet type I, composed of JetA, JetB, JetC and JetD. Expression of Wadjet type I in B.subtilis (strain BEST7003) reduces the transformation efficiency of plasmid pHCMC05 [].
Attachment of sister chromatids to microtubules in the fission yeast Schizosaccharomyces pombe is mediated by the kinetochore complex NMS (Ndc80-MIND-Spc7). Sos7 is a component of the MIND complex and is required for kinetochore targeting of Spc7 [
]. This fungal kinetochore family represented by Sos7 is not present in yeasts belonging to the Saccharomyces complex. Instead, these organisms have proteins homologous to the S. cerevisiae Spc105 interaction partner Kre28.
SCO2 (SNOWY COTYLEDON 2) is a chloroplast protein disulphide isomerase, which is thought to be involved in protein folding [
]. It interacts with LHCB1 (light-harvesting chlorophyll binding 1) and affects chloroplast biogenesis in cotyledons []. It has been shown to have a role in leaf variegation in both Lotus japonicus and Arabidopsis thaliana [].
This family of plant proteins consists of WPP domain-associated proteins (WAPs). WAP interacts through its coiled-coil domain with several WPP-domain containing proteins and it is localized at the Golgi. It is required for complex formation of WPP-domain proteins [
].
This family remains to be characterised. It is found in eukaryotes, and includes human protein ERICH3. In this family of proteins there are two conserved sequence motifs: CCE and PCY.
Treacher Collins Syndrome (TCS) is an autosomal dominant disorder of
craniofacial development, the features of which include conductive hearing loss and cleft palate [
,
]; it is the most common of the human mandibulo-facial dysostosis disorders []. The TCS locus has been mapped to human chromosome 5q31.3-32 and the mutated gene identified (TCOF1) []. To date, 35 mutations have been reported in TCOF1, all but one of which result in the introduction of a premature-termination codon into the predicted protein, Treacle. The observed mutational spectrum supports the hypothesis that TCS results from haploinsufficiency.Treacle is a low complexity protein of 1,411 amino acids whose predicted
protein structure contains a set of highly polar repeated motifs []. These motifs are common to nucleolar trafficking proteins in other species and are predicted to be phosphorylated by casein kinase. In concert with this observation, the full-length TCOF1 protein sequence also contains putative nuclear and nucleolar localisation signals []. Throughout the openreading frame are found mutations in TCS families and several polymorphisms. It has thus been suggested that TCS results from defects in a nucleolar trafficking protein that is critically required during human craniofacial development.
The function of this family of proteins is not known. The crystal structure of the Saccharomyces cerevisiae member, YML079w, revealed a jelly-roll fold [].
This family of plant proteins includes EGG APPARATUS-1 (EA1), which is required for female fertility. It is a small protein involved in short-range signaling required for pollen tube attraction by the female gametophyte. It is exclusively expressed in the egg apparatus [
,
].
C-Jun-amino-terminal kinase (JNK)-interacting protein 3 (JIP3) and 4 (JIP4) are two highly related scaffolding proteins for MAP kinases. They are binding partners for molecular motors kinesin-1 and dynactin, as well as for the small G protein ARF6, which they bind through their leucine zipper II (LZII) region [
,
,
]. ARF6, together with JIP3 and JIP4, regulates membrane-tethered membrane type 1-matrix metalloproteinase exocytosis in cancer invasion [].The function of JIP4 has been shown to be different from that of other JIP proteins. Although JIP4 binds JNK, it does not activate JNK signaling [].
This domain is a variant of the protein kinase domain that is found in fungi (mostly in Basidiomycota and Ascomycota). Proteins containing this domain include CRN8 (crinkler effector protein 8) from Phytophthora infestans [
]. CRN8 is a secreted effector and a kinase that induces cell death when expressed in host plants [,
,
].
PGR5-like protein 1 (PGRL1) is involved in photosynthetic cyclic electron flow, which is driven by PSI (photosystem I). PGRL1 forms homodimers and PGRL1-PGR5 heterodimers. The PGR5-PGRL1 complex mediates the second photosynthetic cyclic electron transport (CET) circuit, accepting electrons from ferredoxin (Fd) and reducing the plastoquinone (PQ) pool, thus acting as an Fd-PQ reductase [
,
]. In Arabidopsis thaliana, there are two orthologues, PGRL1A and PGRLB.
The function of this family, TMEM71, is not known. However, it is predicted to be a transmembrane protein. This family of proteins is found in eukaryotes. Proteins in the family vary between 41 and 291 amino acids in length.
The CRISPR-Cas system is a prokaryotic defense mechanism against foreign genetic elements. The key elements of this defense system are the Cas proteins and the CRISPR RNA. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are a family of DNA direct repeats separated by regularly sized non-repetitive spacer sequences that are found in most bacterial and archaeal genomes [
]. CRISPRs appear to provide acquired resistance against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain sequences complementary to antecedent mobile elements and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA).The defense reaction is divided into three stages. In the adaptation stage, the invader DNA is cleaved, and a piece of it is selected to be integrated as a new spacer into the CRISPR locus, where it is stored as an identity tag for future attacks by this invader. During the second stage (the expression stage), the CRISPR RNA (pre-crRNA) is transcribed and subsequently processed into the mature crRNAs. In the third stage (the interference stage), Cas proteins, together with crRNAs, identify and degrade the invader [
,
,
].The CRISPR-Cas systems have been sorted into three major classes. In CRISPR-Cas types I and III, the mature crRNA is generally generated by a member of the Cas6 protein family. Whereas in system III the Cas6 protein acts alone, in some class I systems it is part of a complex of Cas proteins known as Cascade (CRISPR-associated complex for antiviral defense). The Cas6 protein is an endoribonuclease necessary for crRNA production whereas the additional Cas proteins that form the Cascade complex are needed for crRNA stability [
]. This entry represents the Cas4 family of proteins. Cas4 proteins resembles the RecB family of exonucleases (
) and contains a cysteine-rich motif indicative of DNA binding. As such, Cas4 proteins may function as part of a hypothetical DNA repair system [
,
]. Cas4 from the archaeon Sulfolobus solfataricus has been shown to be a 5' to 3' single stranded DNA exonuclease in vitro, and to contain an iron-sulfur cluster [].Cas4 is one of four protein families (Cas1 to Cas4) that are associated with CRISPR elements and always occur near a repeat cluster, usually in the order cas3-cas4-cas1-cas2.
The CRISPR-Cas system is a prokaryotic defense mechanism against foreign genetic elements. The key elements of this defense system are the Cas proteins and the CRISPR RNA. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are a family of DNA direct repeats separated by regularly sized non-repetitive spacer sequences that are found in most bacterial and archaeal genomes [
]. CRISPRs appear to provide acquired resistance against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain sequences complementary to antecedent mobile elements and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA).The defense reaction is divided into three stages. In the adaptation stage, the invader DNA is cleaved, and a piece of it is selected to be integrated as a new spacer into the CRISPR locus, where it is stored as an identity tag for future attacks by this invader. During the second stage (the expression stage), the CRISPR RNA (pre-crRNA) is transcribed and subsequently processed into the mature crRNAs. In the third stage (the interference stage), Cas proteins, together with crRNAs, identify and degrade the invader [
,
,
].The CRISPR-Cas systems have been sorted into three major classes. In CRISPR-Cas types I and III, the mature crRNA is generally generated by a member of the Cas6 protein family. Whereas in system III the Cas6 protein acts alone, in some class I systems it is part of a complex of Cas proteins known as Cascade (CRISPR-associated complex for antiviral defense). The Cas6 protein is an endoribonuclease necessary for crRNA production whereas the additional Cas proteins that form the Cascade complex are needed for crRNA stability [
]. This entry, typified by YPO2464 of Yersinia pestis, is a CRISPR-associated (Cas) entry strictly associated with the Ypest subtype of CRISPR/Cas locus. It is designated Csy2, for CRISPR/Cas Subtype Ypest protein 2.
The CRISPR-Cas system is a prokaryotic defense mechanism against foreign genetic elements. The key elements of this defense system are the Cas proteins and the CRISPR RNA. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are a family of DNA direct repeats separated by regularly sized non-repetitive spacer sequences that are found in most bacterial and archaeal genomes [
]. CRISPRs appear to provide acquired resistance against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain sequences complementary to antecedent mobile elements and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA).The defense reaction is divided into three stages. In the adaptation stage, the invader DNA is cleaved, and a piece of it is selected to be integrated as a new spacer into the CRISPR locus, where it is stored as an identity tag for future attacks by this invader. During the second stage (the expression stage), the CRISPR RNA (pre-crRNA) is transcribed and subsequently processed into the mature crRNAs. In the third stage (the interference stage), Cas proteins, together with crRNAs, identify and degrade the invader [
,
,
].The CRISPR-Cas systems have been sorted into three major classes. In CRISPR-Cas types I and III, the mature crRNA is generally generated by a member of the Cas6 protein family. Whereas in system III the Cas6 protein acts alone, in some class I systems it is part of a complex of Cas proteins known as Cascade (CRISPR-associated complex for antiviral defense). The Cas6 protein is an endoribonuclease necessary for crRNA production whereas the additional Cas proteins that form the Cascade complex are needed for crRNA stability [
]. This entry, typified by YPO2465 of Yersinia pestis, is a CRISPR-associated (Cas) entry strictly associated with the Ypest subtype of CRISPR/Cas locus. It is designated Csy1, for CRISPR/Cas Subtype Ypest protein 1.
The CRISPR-Cas system is a prokaryotic defense mechanism against foreign genetic elements. The key elements of this defense system are the Cas proteins and the CRISPR RNA. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are a family of DNA direct repeats separated by regularly sized non-repetitive spacer sequences that are found in most bacterial and archaeal genomes [
]. CRISPRs appear to provide acquired resistance against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain sequences complementary to antecedent mobile elements and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA).The defense reaction is divided into three stages. In the adaptation stage, the invader DNA is cleaved, and a piece of it is selected to be integrated as a new spacer into the CRISPR locus, where it is stored as an identity tag for future attacks by this invader. During the second stage (the expression stage), the CRISPR RNA (pre-crRNA) is transcribed and subsequently processed into the mature crRNAs. In the third stage (the interference stage), Cas proteins, together with crRNAs, identify and degrade the invader [
,
,
].The CRISPR-Cas systems have been sorted into three major classes. In CRISPR-Cas types I and III, the mature crRNA is generally generated by a member of the Cas6 protein family. Whereas in system III the Cas6 protein acts alone, in some class I systems it is part of a complex of Cas proteins known as Cascade (CRISPR-associated complex for antiviral defense). The Cas6 protein is an endoribonuclease necessary for crRNA production whereas the additional Cas proteins that form the Cascade complex are needed for crRNA stability [
]. This entry, typified by YPO2463 of Yersinia pestis, is a CRISPR-associated (Cas) entry strictly associated with the Ypest subtype of CRISPR/Cas locus. It is designated Csy3, for CRISPR/Cas Subtype Ypest protein 3.
The CRISPR-Cas system is a prokaryotic defense mechanism against foreign genetic elements. The key elements of this defense system are the Cas proteins and the CRISPR RNA. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are a family of DNA direct repeats separated by regularly sized non-repetitive spacer sequences that are found in most bacterial and archaeal genomes [
]. CRISPRs appear to provide acquired resistance against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain sequences complementary to antecedent mobile elements and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA).The defense reaction is divided into three stages. In the adaptation stage, the invader DNA is cleaved, and a piece of it is selected to be integrated as a new spacer into the CRISPR locus, where it is stored as an identity tag for future attacks by this invader. During the second stage (the expression stage), the CRISPR RNA (pre-crRNA) is transcribed and subsequently processed into the mature crRNAs. In the third stage (the interference stage), Cas proteins, together with crRNAs, identify and degrade the invader [
,
,
].The CRISPR-Cas systems have been sorted into three major classes. In CRISPR-Cas types I and III, the mature crRNA is generally generated by a member of the Cas6 protein family. Whereas in system III the Cas6 protein acts alone, in some class I systems it is part of a complex of Cas proteins known as Cascade (CRISPR-associated complex for antiviral defense). The Cas6 protein is an endoribonuclease necessary for crRNA production whereas the additional Cas proteins that form the Cascade complex are needed for crRNA stability [
]. This entry represents the Cse2 family of Cas proteins, which includes CT1973 from Chlorobium tepidum. These proteins are found in the CRISPR/Cas subtype Ecoli regions of many bacteria (most of which are mesophiles), and not in Archaea []. This is also known as CasB or Cse2 Type I-E [].
The CRISPR-Cas system is a prokaryotic defense mechanism against foreign genetic elements. The key elements of this defense system are the Cas proteins and the CRISPR RNA. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are a family of DNA direct repeats separated by regularly sized non-repetitive spacer sequences that are found in most bacterial and archaeal genomes [
]. CRISPRs appear to provide acquired resistance against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain sequences complementary to antecedent mobile elements and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA).The defense reaction is divided into three stages. In the adaptation stage, the invader DNA is cleaved, and a piece of it is selected to be integrated as a new spacer into the CRISPR locus, where it is stored as an identity tag for future attacks by this invader. During the second stage (the expression stage), the CRISPR RNA (pre-crRNA) is transcribed and subsequently processed into the mature crRNAs. In the third stage (the interference stage), Cas proteins, together with crRNAs, identify and degrade the invader [,
,
].The CRISPR-Cas systems have been sorted into three major classes. In CRISPR-Cas types I and III, the mature crRNA is generally generated by a member of the Cas6 protein family. Whereas in system III the Cas6 protein acts alone, in some class I systems it is part of a complex of Cas proteins known as Cascade (CRISPR-associated complex for antiviral defense). The Cas6 protein is an endoribonuclease necessary for crRNA production whereas the additional Cas proteins that form the Cascade complex are needed for crRNA stability [
]. This entry represents the Cse1 family of Cas proteins, which includes CT1972 from Chlorobium tepidum [
]. These proteins are found in the CRISPR/Cas subtype Escherichia coli regions of many bacteria (most of which are mesophiles), and not in Archaea. This is also known as CasA, or Cse1 Type I-E [].
The CRISPR-Cas system is a prokaryotic defense mechanism against foreign genetic elements. The key elements of this defense system are the Cas proteins and the CRISPR RNA. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) are a family of DNA direct repeats separated by regularly sized non-repetitive spacer sequences that are found in most bacterial and archaeal genomes [
]. CRISPRs appear to provide acquired resistance against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain sequences complementary to antecedent mobile elements and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA).The defense reaction is divided into three stages. In the adaptation stage, the invader DNA is cleaved, and a piece of it is selected to be integrated as a new spacer into the CRISPR locus, where it is stored as an identity tag for future attacks by this invader. During the second stage (the expression stage), the CRISPR RNA (pre-crRNA) is transcribed and subsequently processed into the mature crRNAs. In the third stage (the interference stage), Cas proteins, together with crRNAs, identify and degrade the invader [
,
,
].The CRISPR-Cas systems have been sorted into three major classes. In CRISPR-Cas types I and III, the mature crRNA is generally generated by a member of the Cas6 protein family. Whereas in system III the Cas6 protein acts alone, in some class I systems it is part of a complex of Cas proteins known as Cascade (CRISPR-associated complex for antiviral defense). The Cas6 protein is an endoribonuclease necessary for crRNA production whereas the additional Cas proteins that form the Cascade complex are needed for crRNA stability []. This entry represents a minor class of Cas proteins, known as Cas8b [
], found in at least five prokaryotic genomes: Methanosarcina mazei, Sulfurihydrogenibium azorense, Thermotoga maritima, Carboxydothermus hydrogenoformans, and Dictyoglomus thermophilum, the first of which is archaeal while the rest are bacterial []. Cas8b is a large subunit of the Type-I-B Cascade complex found in Clostridium thermocellum and Methanococcus maripaludis [].
Human Reticulon 4 Interacting Protein 1 is a member of the medium chain dehydrogenase/ reductase (MDR) family. Reticulons are endoplasmic reticulum associated proteins involved in membrane trafficking and neuroendocrine secretion [
,
]. The MDR/zinc-dependent alcohol dehydrogenase-like family, which contains the zinc-dependent alcohol dehydrogenase (ADH-Zn) and related proteins, is a diverse group of proteins related to the first identified member, class I mammalian ADH [
]. MDRs display a broad range of activities and are distinguished from the smaller short chain dehydrogenases (~ 250 amino acids vs. the ~ 350 amino acids of the MDR) []. The MDR proteins have 2 domains: a C-terminal NAD(P) binding-Rossmann fold domain of a beta-alpha form and an N-terminal catalytic domain with distant homology to GroES [].
Phosphatidylinositol transfer protein (PITP) is a ubiquitous cytosolic protein, thought to be involved in transport of phospholipids from their site of synthesis in the endoplasmic reticulum and Golgi to other cell membranes [
]. More recently, PITP has been shown to be an essential component of the polyphosphoinositide synthesis machinery and is hence required for proper signalling by epidermal growth factor and f-Met-Leu-Phe, as well as for exocytosis. The role of PITP in polyphosphoinositide synthesis may also explain its involvement in intracellular vesicular traffic [].
Vps Four-Associated 1, Vfa1, in yeast, is an endosomal protein that interacts with the AAA-ATPase Vps4. It would seem to be involved in regulating the trafficking of other proteins to the endocytic vacuole [
]. There is a CCCH zinc finger at the N terminus.
HIRIP3 interacts with the HIRA histone chaperone [
]. It can be phosphorylated by the serine-threonine kinase CK2 and may be involved in chromatin metabolism [].
Druantia type I is an antiviral defense system composed of DruA, DruB, DruC, DruD and DruE. Expression of Druantia in E.coli (strain MG1655) confers resistance to phage lambda, SECphi18, SECphi27 and T4. This entry represents DruA [
].
This entry represents the bifunctional protein HldE. It comprises D-beta-D-heptose 7-phosphate kinase [intenz:2.7.1.-] and D-beta-D-heptose 1-phosphate adenosyltransferase [intenz:2.7.7.-]activities.
This family of proteins is involved in sporulation. It may contribute to the formation and stability of the thick peptidoglycan layer between the two membranes of the spore, known as the cortex [
]. In Bacillus subtilis its expression is regulated by sigma-E [].
This entry includes FMC1 homologues from animals. The budding yeast Fmc1 (not included in this entry) is a nuclear protein required for the assembly/stability of yeast mitochondrial F(1)-ATPase in heat stress conditions [
].
This entry represents a predicted immunity protein, with an alpha+beta fold (mostly alpha helices). The protein is present in polymorphic toxin systems as an immediate gene neighbour of the toxin gene [
].
This entry represents a predicted immunity protein, with a mostly all-alpha fold, present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene [
].
This entry represents a predicted immunity protein, with an all-alpha fold, present in bacterial polymorphic toxin systems as an immediate neighbour of the toxin [
].
This entry represents a predicted immunity protein, with a mostly all-alpha fold, present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene [
].
Swc3 is a component of the SWR1 complex which mediates the ATP-dependent exchange of histone H2A for the H2A variant HZT1 leading to transcriptional regulation of selected genes by chromatin remodeling [
,
].It's worth noting that SWC3 has been used to refer to both SWC3/YAL011W, whose gene product is involved in chromatin remodeling and ER biogenesis, and ALR1/YOL130W, a plasma membrane transporter.
The PyrR protein from Bacillus subtilis and many other bacteria is a bifunctional protein. Its primary function is the regulation of expression of pyrimidine biosynthetic (pyr) genes by binding to specific sites on pyr mRNA in a uridine nucleotide-dependent manner and altering the folding of downstream RNA to promote termination of transcription. PyrR also catalyzes the uracil phosphoribosyltransferase (UPRTase) reaction () even though it bears little amino acid sequence similarity to other bacterial UPRTases [
].
The PrsA protein of Bacillus subtilis is an essential membrane-bound lipoprotein that is assumed to assist post-translocational folding of exported proteins and stabilise them in the compartment between the cytoplasmic membrane and cell wall. This folding activity is consistent with the homology of a segment of PrsA with parvulin-type peptidyl-prolyl cis/trans isomerases (PPIase). PrsA is a PPIase, but the essential role in vivo seems to depend on some non-PPIase activity of both the parvulin-like and flanking domains [
].
This entry represents the hypothetical protein AF_0941 from the hyperthermophilic sulphate-reducing archaeon Archaeoglobus fulgidus. The structure of this protein consists of several α-helices arranged in an orthogonal bundle.
CBP1 is regulator of transcription initiation in plants that shows no homology to animal or yeast proteins. CBP1, via interaction with CCG and the Mediator complex, connects transcription factors and the Pol II machinery to regulate pollen tube attraction [
].
This entry represents a predicted immunity protein with an alpha+beta fold and conserved tryptophan,tyrosine and an acidic residues. Proteins containing this domain are present in bacterial polymorphic toxin systems as an immediate gene neighbour of the toxin gene, which usually contains toxin domains of the ColD/E5, Tox-REase-4, Ntox49 or Ntox14 families [
]. The domain is also found in heterogeneous polyimmunity loci.
This protease is found in genome polyproteins of potyviruses. The genome polyprotein contains: N-terminal protein (P1), helper component protease
(, HC-PRO), protein P3, 6KD protein (6K1), cytoplasmic inclusion protein (CI), 6KD protein 2 (6K2), genome-linked protein (VPG), nuclear inclusion protein A (), nuclear inclusion protein B (
) and coat protein (CP).
The coat protein is at the C terminus of the polyprotein.
Hexon (also known as protein II) is a major capsid protein that self-associates to form 240 hexon trimers, each in the shape of a hexagon, building most of the pseudo T=25 capsid [
].
This is a family of immunity proteins, mainly from Bacillus spp, such as WapI. The immunity protein WapI specifically neutralizes its cognate toxin WapA to protect wapA+ cells from autoinhibition. WapA carries a C-terminal toxin domain (WapA-CT) that inhibits the growth of neighbouring cells [
].
Matrix protein (M1) of influenza virus is a bifunctional membrane/RNA-binding protein that mediates the encapsidation of RNA-nucleoprotein cores into the membrane envelope. It is therefore required that M1 binds both membrane and RNA simultaneously [
]. M1 is comprised of two domains connected by a linker sequence. The N-terminal domain has a multi-helical structure that can be divided into two subdomains []. The C-terminal domain also contains an α-helical structure.
This entry is found on Crisp proteins which contain
and has been termed the Crisp domain. It is found in the mammalian reproductive tract and the venom of reptiles, and has been shown to regulate ryanodine receptor Ca2+ signalling [
]. It contains 10 conserved cysteines which are all involved in disulphide bonds and is structurally related to the ion channel inhibitor toxins BgK and ShK [].
There are currently no experimental data for members of this group or their homologues. However, these
proteins are implicated in virulence/pathogenicity because RhuM is encoded in the SPI-3 pathogenicity island inSalmonella typhimurium [
,
].
The poxvirus F1 family members are related to Vaccinia virus protein F1L, which interacts with and inhibits NLR-mediated interleukin-1 beta/IL1B production in infected cells. F1L suppresses mitochondrial-dependent apoptosis by binding to the BH3 domain of host BAK and prevents BAK from binding active BAX [
,
].
This is a family of proteins found in viruses. Members of this family such as NS3 found in Junonia coenia have been shown to be involved in viral DNA replication. Generation of deletion mutants and replicative cycle analysis show that NS3 is required for viral DNA replication [
]. Bioinformatics analysis of Bombyx mori densovirus protein NS3, show that it has two putative zinc-finger motifs, 6 putative N glycosylation sites, and 4 putative phosphorylation sites [].
Phloem protein 2 (PP2) is one of the most abundant and enigmatic proteins in the phloem sap. PP2 is translocated in the assimilate stream where its lectin activity or RNA-binding properties can exert effects over long distances. PP2-like genes have been identified in many plant species, indicating a wide distribution of PP2 genes in the plant kingdom [
].This entry represents PP2 and PP2-like proteins.
Protein arginine methyltransferases (PRMTs) are enzymes that transfer methyl groups to the arginine residues of histones and other proteins. Arginine methylation is an important posttranslational modification process that plays functional roles in transcriptional control, splicing, DNA repair, and signaling [
,
,
]. PRMTs use S-adenosylmethionine(SAM or AdoMet)-dependent methylation to modify the guanidino nitrogens of the arginine side chain by adding one or two methyl groups [
]. According to their methylation status, the PRMT enzymes are classified into different group types. While the type-I PRMT enzymes catalyse the formation of monomethylarginine (MMA) and asymmetric dimethylarginine (aDMA), the type-II PRMT enzymes form MMA and symmetric dimethylarginine (sDMA). The enzymes PRMT1, PRMT3, PRMT4, PRMT6 and PRMT8 belong to the type-I and PRMT5, PRMT7 and PRMT9 to type-II.
Ribosomes are the particles that catalyse mRNA-directed protein synthesis in all organisms. The codons of the mRNA are exposed on the ribosome to allow tRNA binding. This leads to the incorporation of amino acids into the growing polypeptide chain in accordance with the genetic information. Incoming amino acid monomers enter the ribosomal A site in the form of aminoacyl-tRNAs complexed with elongation factor Tu (EF-Tu) and GTP. The growing polypeptide chain, situated in the P site as peptidyl-tRNA, is then transferred to aminoacyl-tRNA and the new peptidyl-tRNA, extended by one residue, is translocated to the P site with the aid the elongation factor G (EF-G) and GTP as the deacylated tRNA is released from the ribosome through one or more exit sites [
,
]. About 2/3 of the mass of the ribosome consists of RNA and 1/3 of protein. The proteins are named in accordance with the subunit of the ribosome which they belong to - the small (S1 to S31) and the large (L1 to L44). Usually they decorate the rRNA cores of the subunits. Many ribosomal proteins, particularly those of the large subunit, are composed of a globular, surfaced-exposed domain with long finger-like projections that extend into the rRNA core to stabilise its structure. Most of the proteins interact with multiple RNA elements, often from different domains. In the large subunit, about 1/3 of the 23S rRNA nucleotides are at least in van der Waal's contact with protein, and L22 interacts with all six domains of the 23S rRNA. Proteins S4 and S7, which initiate assembly of the 16S rRNA, are located at junctions of five and four RNA helices, respectively. In this way proteins serve to organise and stabilise the rRNA tertiary structure. While the crucial activities of decoding and peptide transfer are RNA based, proteins play an active role in functions that may have evolved to streamline the process of protein synthesis. In addition to their function in the ribosome, many ribosomal proteins have some function 'outside' the ribosome [
,
].The small subunit ribosomal proteins can be categorised as: primary binding proteins, which bind directly and independently to 16S rRNA; secondary binding proteins, which display no specific affinity for 16S rRNA, but its assembly is contingent upon the presence of one or more primary binding proteins; and tertiary binding proteins, which require the presence of one or more secondary binding proteins and sometimes other tertiary binding proteins. The small ribosomal subunit protein S19 contains 88-144 amino acid residues. In Escherichia coli, S19 is known to form a complex with S13 that binds strongly to 16S ribosomal RNA. Experimental evidence [
] has revealed that S19 is moderately exposed on the ribosomal surface, and is designated a secondary rRNA binding protein. S19 belongs to a family of ribosomal proteins [,
] that includes: eubacterial S19; algal and plant chloroplast S19; cyanelle S19; archaebacterial S19; plant mitochondrial S19; and eukaryotic S15 ('rig' protein).
Ribosomal protein L11 is one of the proteins from the large ribosomal subunit. In Escherichia coli, L11 is known to bind directly to the 23S rRNA and plays a significant role during initiation, elongation, and termination of protein synthesis. It belongs to a family of ribosomal proteins which, on the basis of sequence similarities [
], groups bacteria, plant chloroplast, red algal chloroplast, cyanelle and archaeabacterial L11; and mammalian, plant and yeast L12 (YL15). L11 is a protein of 140 to 165 amino-acid residues. L11 consists of a 23S rRNA binding C-terminal domain and an N-terminal domain that directly contacts protein synthesis factors. These two domains are joined by a flexible linker that allows inter-domain movement during protein synthesis. While the C-terminal domain of L11 binds RNA tightly, the N-terminal domain makes only limited contacts with RNA and is proposed to function as a switch that reversibly associates with an adjacent region of RNA [,
,
,
]. In E. coli, the C-terminal half of L11 has been shown [] to be in an extended and loosely folded conformation and is likely to be buried within the ribosomal structure.Ribosomal protein L11, together with proteins L10 and L7/L12, and 23S rRNA, form the L7/L12 stalk on the surface of the large subunit of the ribosome. The homologous eukaryotic cytoplasmic protein is also called 60S ribosomal protein L12, which is distinct from the L12 involved in the formation of the L7/L12 stalk. The C-terminal domain (CTD) of L11 is essential for binding 23S rRNA, while the N-terminal domain (NTD) contains the binding site for the antibiotics thiostrepton and micrococcin. L11 and 23S rRNA form an essential part of the GTPase-associated region (GAR). Based on differences in the relative positions of the L11 NTD and CTD during the translational cycle, L11 is proposed to play a significant role in the binding of initiation factors, elongation factors, and release factors to the ribosome. Several factors, including the class I release factors RF1 and RF2, are known to interact directly with L11. In eukaryotes, L11 has been implicated in regulating the levels of ubiquinated p53 and MDM2 in the MDM2-p53 feedback loop, which is responsible for apoptosis in response to DNA damage. In bacteria, the "stringent response"to harsh conditions allows bacteria to survive, and ribosomes that lack L11 are deficient in stringent factor stimulation [
,
,
,
,
,
,
,
,
,
,
,
].
This family represents eukaryotic protein disulphide isomerases retained in the endoplasmic reticulum (ER) and other closely related forms [
]. Some members have been assigned alternative or additional functions such as prolyl 4-hydroxylase [,
]. Members of this family have at least two protein-disulphide domains, each similar to thioredoxin but with the redox-active disulphide in the motif PWCGHCK, and an ER retention signal at the extreme C terminus (KDEL, HDEL, and similar motifs).
