This entry represents the cell division protein ZapA. ZapA interacts with FtsZ, where FtsZ is part of a mid-cell cytokinetic structure termed the Z-ring that recruits a hierarchy of fission related proteins early in the bacterial cell cycle. ZapA drives the polymerisation and filament bundling of FtsZ, thereby contributing to the spatio-temporal tuning of the Z-ring. ZapA is recruited early at mid-cell but it is not essential for cell division [
]. In sporulating cells, ZapA localizes near the cell poles. The proteins in this entry belongs to the ZapA Type 2 subfamily.
BPLF1, the Epstein-Barr-virus-encoded member of this protease family, is a deneddylase that regulates virus production by modulating the activity of cullin-RING ligases. Homologues encoded by other herpesviruses share the deneddylase activity [
].
This entry represents the C-terminal domain of Circadian clock protein KaiA.Cyanobacteria are the most primitive organisms known to exhibit circadian
rhythms. KaiA, kaiB and kaiC constitute the circadian clockmachinery in cyanobacteria, and kaiA activates kaiBC expression whereas kaiC
represses 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 to
beta5) parallel β-sheet flanked by two groups of α-helices (alpha1,alpha4 and alpha2, alpha3) packed on either side of the β-sheet and an
additional 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 bacterial
response 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 activation
most likely involves direct protein-protein interactions of the N-terminal
domain 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 protein
folding motif.
DREB2A-Interacting Proteins (DRIPs) are E3 ubiquitin-protein ligases that act as negative regulators of the response to water stress. This family includes DRIP1, DRIP2 and the DRIP homologue (DRIPH) At3g23060 from Arabidopsis, which mediate ubiquitination and subsequent proteasomal degradation of the drought-induced transcriptional activator Dehydration-Responsive Element-Binding Protein 2A (DREB2A) [
,
,
]. DRIP1 and DRIP2 are functionally redundant. DREB2A regulates the expression of stress-inducible genes via the dehydration-responsive elements and requires posttranslational modification for its activation. DRIPs contain a RING finger, and a RING finger- and WD40-associated ubiquitin-like (RAWUL) domain [,
]. The RAWUL domain is responsible for the protein interaction with DREB2A.
Members of this family are radical SAM/SPASM domain proteins from a cassette restricted to the genus Geobacter. Genes always found adjacent include a non-radical SAM protein with a closely related SPASM domain and a short stretch of N-terminal homology as well to this family, and also a PqqD-like protein. The three-gene cassette is designated GeoRSP for the genus Geobacter, this radical SAM protein, the SPASM domain protein, and the PqqD family protein.
This entry represents the N-terminal domain of KaiA. Cyanobacteria are the most primitive organisms known to exhibit circadian
rhythms. KaiA, kaiB and kaiC constitute the circadian clockmachinery in cyanobacteria, and kaiA activates kaiBC expression whereas kaiC
represses it []. Apparent homologues of kaiB and kaiC are found amongnoncyanobacterial eubacteria and the archaea. However kaiA appears confined
within 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 sequence
conservation in the amino-terminal 200 residues of these proteins but a highdegree 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 to
beta5) parallel β-sheet flanked by two groups of α-helices (alpha1,alpha4 and alpha2, alpha3) packed on either side of the β-sheet and an
additional 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 bacterial
response 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 activation
most 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. It
adopts 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 protein
folding motif.
Members of this protein family are exclusive to the Bacteroidetes phylum (previously Cytophaga-Flavobacteria-Bacteroides). GldN is a protein linked to a type of rapid surface gliding motility found in certain Bacteroidetes, such as Cytophaga johnsonae (Flavobacterium johnsoniae) and Cytophaga hutchinsonii. Knockouts of GldN abolish the gliding phenotype [
]. Gliding motility appears closely linked to chitin utilization in the model species C. johnsonae. Bacteroidetes with members of this protein also include those which are not believed to express the gliding phenotype, such as Prevotella intermedia and Porphyromonas gingivalis (Bacteroides gingivalis).
The crystal structure of the unusual penicillin-binding protein (PBP) Tp47 from Treponema pallidum revealed a unique structure different to any other known PBP, and thus it appears to represent an entirely new class of PBP. Tp47 consists of four distinct domains (A-D) arranged to give the molecule a crab-like appearance. Domain D, like domain C, features an immunoglobulin fold. In contrast to domain C it contains only the characteristic seven-stranded barrel and short loops. As in domain C, a single α-helical turn is inserted between strands 2 and 3 [
]. Domain D is rather isolated as it only interacts with domain C via an ionic interaction between Arg-330 and Glu-404 in the linker region. This explains the large degree of motion observed for this domain.The abundance of hydrophobic residues and the immunoglobulin fold of domain D suggests that it mediates protein-protein interactions. In addition its location, flexibility, and relative disposition indicate a function other that PBP and beta-lactamase activities [
]. It is thought to have an haemagglutination activity.
This is the first domain in Tp47, an unusual penicillin-binding protein (PBP) from Treponema pallidum. It is mainly composed of β-strands and is sequentially non-contiguous. The first three domains in Tp47 interact with each other through intimate domain-domain interfaces. Domain A contacts domain B through its N-terminal segment. Domain A also interacts tightly with domain C. Tp47 is unusual in that it displays beta-lactamase activity, and thus it does not fit the classical structural and mechanistic paradigms for PBPs. Tp47 appears to represent a new class of PBP [
].
Sporulation-specific protein 71, N-terminal domain
Type:
Domain
Description:
This entry represents the N-terminal domain of the sporulation-specific protein 71 (Spo71) from fungi. In many members this domain is associated with a Pleckstrin-homology (PH) domain. Spo71 is required for spore wall formation during sporulation [
,
,
].
Domain C is the largest domain in this unusual penicillin-binding protein (PBP), Tp47. This domain is mainly characterised by an immunoglobulin fold with two opposing β-sheets that form the typical barrel-like structure. In contrast to the classical immunoglobulin fold, however, this has an additional β-strand inserted after strand 3. Also, the strands are connected by rather large loops. Helices are inserted between strands 2 and 3 and between strands 4 and 5. Domain C interacts with domain B via a surface that has a slightly concave, goblet-like shape in addition to interacting tightly with domain A and weakly with domain D. Tp47 is unusual in that it displays beta-lactamase activity, so it does not fit the classical structural and mechanistic paradigms for PBPs, and thus Tp47 appears to represent a new class of PBP [
].
Glutathione-regulated potassium-efflux system protein KefB
Type:
Family
Description:
The CPA2 family is a moderately large family (over 100 sequenced members) from bacteria, archaea and eukaryotes. Among the functionally well-characterised members of the family are (1) the KefB/KefC K+ efflux proteins of Escherichia coli which may be capable of catalysing both K+/H+ antiport and K+ uniport, depending on conditions [
,
], (2) the Na+/H+ antiporter of Enterococcus hirae [] and (3) the K+/H+ antiporter of Saccharomyces cerevisiae. It has been proposed that under normal physiological conditions, these proteins may function by essentially the same mechanism [].KefC and KefB of E. coli are responsible for glutathione-gated K+ efflux [
,
]. Each of these proteins consists of a transmembrane hydrophobic N-terminal domain, and a less well-conserved C-terminal hydrophilic domain. Each protein interacts with a second protein encoded by genes that overlap the gene encoding the primary transporter. The KefB ancillary protein is YheR. The ancillary proteins stimulate transport activity about 10-fold []. They are important for cell survival during exposure to toxic metabolites, possibly because they can release K+, allowing H+ uptake. Activation of the KefB or KefC K+ efflux system only occurs in the presence of glutathione and a reactive electrophile such as methylglyoxal or N-ethylmaleimide. Formation of the methylglyoxal-glutathione conjugate, S-lactoylglutathione, is catalysed by glyoxalase I, and S-lactoylglutathione activates KefB and KefC []. H+ uptake (acidification of the cytoplasm) accompanying or following K+ efflux may serve as a further protective mechanism against electrophile toxicity [,
]. Inhibition of transport by glutathione is enhanced by NADH []. This entry represents the Glutathione-regulated potassium-efflux system protein KefB.
This family of proteins is found in eukaryotes. Proteins in this family are typically around 140 amino acids in length. The human member of this family is C19orf69.
This family of proteins interacts with cannabinoid receptor 1 (CNR1). In humans, there are two isoforms, CRIP1a and CRIP1b. CRIP1a, but not CRIP1b, suppresses cannabinoid receptor CNR1-mediated tonic inhibition of voltage-gated calcium channels [
].
ADP-ribosylation factor GTPase-activating protein AGD14-like
Type:
Family
Description:
This entry represents a group of plant ADP-ribosylation factor GTPase-activating proteins, including AGD14 from Arabidopsis. Arabidopsis contains 15 proteins with ArfGAP domains (AGDs) which can be divided into four distinct classes based on phylogenetic analysis. AGD14 belongs to class 4 together with AGD15 in which the AGD comprises almost the entire open reading frames of these proteins. In AtAGD14, the AGD is followed by an apparent membrane-spanning α-helix, suggesting this ArfGAP could be an integral membrane protein [
].
This group represents a multidomain scavenger receptor-like protein only found in Apicomplexa parasites. PxSR from the malaria parasite has not only a role in sporogonic development, it may also have a multiplicity of functions [
].
TviA from Salmonella typhi is a transcriptional activator of the viaB operon [
] and regulates virulence factors outside SPI-7, including the flagellar regulon []. Gene regulation of virulence factors enables S. typhi to conceal a pathogen-induced process from being sensed by the inflammasome, a protein complex responsible for activation of inflammatory processes [,
].
Bacteria have numerous mechanisms to resist bacteriophage infection. While most are based on preventing infection in the first place, the abortive infection (Abi) systems provide protection by the abortion of an existing phage infection [
]. Typically, these Abi systems target a crucial step of phage multiplication such as replication, transcription or translation, and lead to the death of the infected cell.The AbiD protein provides resistance to phage infection by interfering with a phage-encoded endonuclease, while AbiF interferes with DNA replication [
,
,
,
].
Bacteria have numerous mechanisms to resist bacteriophage infection. While most are based on preventing infection in the first place, the abortive infection (Abi) systems provide protection by the abortion of an existing phage infection [
]. Typically, these Abi systems target a crucial step of phage multiplication such as replication, transcription or translation, and lead to the death of the infected cell.These protein sequences, found in various bacterial species, are similar to those of the AbiD and AbiF proteins from Lactococcus species [
,
]. The proteins are thought to have helix-turn-helix motifs, found in many DNA-binding proteins, allowing them to perform their function [].
This entry represents a protein that is conserved in bacteria. The function is not known, but several members are annotated as being YdgK or a homologue thereof and associated to the inner membrane. This signature also matches proteins that are described as transglutaminase-like enzymes, although this could not be confirmed.
This entry represents a group of proteins mainly found in Bacilli, including Uncharacterized protein YtmB from Bacillus subtilis. Its function is unknown.
This entry represents Sm-like protein Lsm1 and Lsm8. Lsm8 is found in the nuclear Lsm2-8 complex, which associates with multiple snRNP complexes containing the U6 snRNA (U4/U6 snRNP, U4/U6.U5 snRNP, and free U6 snRNP). The Lsm2-8 complex binds and stabilizes the 3'-terminal poly(U) tract of U6 snRNA and facilitates the assembly of U4-U6 di-snRNP and U4-U6-U5 tri-snRNP [
,
,
].Lsm1 can be found in the cytoplasmic Lsm1-7 complex, which associates with deadenylated mRNA and promotes decapping in the 5'-3' mRNA decay pathway [
,
]. The Sm and the Lsm proteins, characterised by the Sm-domain, have RNA-related functions. The Sm heptamer ring associates with four (U1, U2, U4, U5) snRNPs, while Lsm2-8 heptamer is part of the U6 snRNP. Another Lsm heptameric complex, Lsm1-7, which differs from Lsm2-8 by one Lsm protein, functions in mRNA decapping, a crucial step in the mRNA degradation pathway [
].
This entry represents small proteins with unknown function and appear to be restricted to a family of Enterobacterial proteins. It has a highly conserved sequence. Some proteins are annotated as YobF and may be involved in stress responses in E. coli.
AMP-activated protein kinase, glycogen-binding domain
Type:
Domain
Description:
This domain can be found in AMP-activated protein kinases and CRP1/MDG1 family members. The surface of this domain reveals a carbohydrate-binding pocket [
].
This is a family proteins of unknown function which includes predicted surface proteins (often lipoproteins) from Listeria monocytogenes, Listeria innocua, Enterococcus faecalis (Streptococcus faecalis), Lactobacillus plantarum, Mycoplasma spp., Helicobacter hepaticus, and other species. Eukaryotic sequences are also included in this family. Many proteins contain a tandem peptide repeat sequence of 25 or 26 residues.
This entry includes 30S ribosomal proteins from plant mitochondria and plastids, closely related to bacterial ribosomal small subunit protein bTHX (previously THX). Proteins in this entry have additional N-terminal transit peptides [
].
This entry includes Escherichia coli HscC (also called heat shock cognate protein C, Hsc62, or YbeW) and the the putative DnaK-like protein Escherichia coli ECs0689. It belongs to the heat shock protein 70 (Hsp70) family of chaperones that assist in protein folding and assembly and can direct incompetent 'client' proteins towards degradation. Typically, Hsp70s have a nucleotide-binding domain (NBD) and a substrate-binding domain (SBD). The nucleotide sits in a deep cleft formed between the two lobes of the NBD. The two subdomains of each lobe change conformation between ATP-bound, ADP-bound, and nucleotide-free states. ATP binding opens up the substrate-binding site; substrate-binding increases the rate of ATP hydrolysis [
,
].Hsp70 chaperone activity is regulated by various co-chaperones: J-domain proteins and nucleotide exchange factors (NEFs). Two genes in the vicinity of the HscC gene code for potential cochaperones: J-domain containing proteins, DjlB/YbeS and DjlC/YbeV. HscC and its co-chaperone partners may play a role in the SOS DNA damage response [
].
Protein LOW PSII ACCUMULATION 3 (LPA3) is probably located in chloroplast stroma or associated with thylakoid membranes. LPA3 works cooperatively with LPA2 as auxiliary proteins in the incorporation of psbC (also known as CP43) into PSII via interaction with cpSRP translocase ALB3. They are thought to be also involved in synthesis and assembly of psbC [
].
This entry represents the N-terminal domain of uncharacterised proteins, such as YccS, with similarities to the fusaric acid resistance protein. These proteins are lodged in the inner membrane [
].
This entry includes a group of plant proteins, such as the PWWP domain containing protein PWWP2 (At1g51745, also known SL1) from Arabidopsis thaliana [
,
]. Its exact function is not known. It is part of PEAT complexes (for PWWPs-EPCRs-ARIDs-TRBs) which mediate histone deacetylation and heterochromatin condensation to facilitate heterochromatin silencing. These complexes repress the production of small interfering RNAs (siRNAs) and DNA methylation [].
Mitochondrial phosphate carrier protein Pic2/Mir1-like
Type:
Family
Description:
This entry represents a group of mitochondrial phosphate carrier proteins, including Mir1 and Pic2 from budding yeasts. They are copper and phosphate carriers that imports copper and inorganic phosphate into mitochondria [
,
].
ER degradation-enhancing alpha-mannosidase-like protein 1/2/3
Type:
Family
Description:
This entry represents a group of alpha-1,2-specific exomannosidases that are involved in endoplasmic reticulum-associated degradation (ERAD), including EDEM1/2/3 from humans, Mnl1 from yeasts and MNS4/5 from Arabidopsis. Mnl1 forms a complex with Pdi1 to process unfolded protein-bound Man8GlcNAc2 oligosaccharides to Man7GlcNAc2, promoting degradation in unfolded protein response [
]. In humans, mannose trimming from Man8GlcNAc2 to Man7GlcNAc2 is performed mainly by EDEM3 and to a lesser extent by EDEM1, while EDEM2 catalyses the first mannose trimming step from Man9GlcNAc2 []. EDEM1 has been shown to recognise and deliver misfolded proteins to the SEL1L-containing ERAD complex []. MNS4/5 function in the formation of unique N-glycan structures that are specifically recognized by components of the endoplasmic reticulum-associated degradation (ERAD) machinery, which leads to the degradation of misfolded glycoproteins [].
This entry represents the N-terminal domain of animal Sun1 proteins. Sun1 is a nuclear envelope (NE) protein that interacts with nuclear lamin A and cytoplasmic nesprins to provide a physical connection between the nuclear lamina and the cytoskeleton [
].
Proteins in this family contains Xin repeats, which define an actin-binding motif. In humans two Xin-repeat proteins have been identified, XIRP1 and XIRP2. They are expressed during early developmental stages of cardiac and skeletal muscles [
] and have an important role in cardiac development and function []. They bind to and stabilise F-actin [].The homologues in mouse and chicken localise in the adherens junction complex of the intercalated disc in cardiac muscle and in the myotendon junction of skeletal muscle. Mouse Xin may co-localise with Vinculin which is known to attach the actin to the cytoplasmic membrane [
]. Human XIRP1 binds the EVH1 domains of Ena/VASP proteins and filamin C []. It also binds the SH3 domain of nebulin and nebulette []. The multiplicity of binding partners suggests that Xin acts as a multi-adaptor protein during myofibril development and repair [].
This entry represents a group of eukaryotic proteins that are typically between 427 and 674 amino acids in length. There are two completely conserved residues (D and I) that may be functionally important.
Human HSPA13 (also called 70kDa heat shock protein 13, STCH, or 'stress 70 protein chaperone, microsome-associated, 60kDa') belongs to the heat shock protein 70 (HSP70) family of chaperones that assist in protein folding and assembly and can direct incompetent 'client' proteins towards degradation. Typically, HSP70s have a nucleotide-binding domain (NBD) and a substrate-binding domain (SBD). The nucleotide sits in a deep cleft formed between the two lobes of the NBD. STCH contains an NBD but lacks an SBD [
]. STCH may function to regulate cell proliferation and survival, and modulate the TRAIL-mediated cell death pathway. The HSPA13 gene is a candidate stomach cancer susceptibility gene; a mutation in the NBD coding region of HSPA13 has been identified in stomach cancer cells []. The NBD of HSPA13 interacts with the ubiquitin-like proteins Chap1 and Chap2, implicating HSPA13 in regulating cell cycle and cell death events []. HSPA13 is induced by the Ca2+ ionophore A23187 [].
This entry represents the N-terminal region of the cilium assembly protein DZIP1, which acts as a molecular adapter that recruits protein complexes required for cilium assembly and function to the cilium basal body [
,
,
,
]. It also recruits the BBSome, a complex involved in cilium biogenesis, by bridging it to PCM1 at the centriolar satellites of the cilium []. DZIP1 is involved in spermatogenesis through its role in organization of the basal body and assembly of the sperm flagellum [] and it is also indirectly involved in heart development through its function in ciliogenesis []. Zebrafish Dzip1 acts as a permissive factor that is required for the proper regulation of Hedgehog (Hh) target genes in response to Hh signals []. It is required for establishment of left-right asymmetry during embryogenesis and has a role in primary cilium formation [].
This entry represents a domain found in the C-terminal region of the microcin J25-processing protein McjB from Escherichia coli. This domain is related to the transglutaminase-like domain .
Microcin J25 (MccJ25) is a lasso peptide secreted by Escherichia coli which exerts a potent antibacterial activity by blocking RNA polymerase [
]. McjB is involved in microcin maturation, which implies cleavage of McjA and head-tail linkage of the 21-residue pro-MccJ25 [,
].
Izumo sperm-egg fusion protein 1 (IZUMO1) is an essential sperm cell-surface protein required for fertilisation by acting as a ligand for IZUMO1R/JUNO receptor on eggs [
]. It is a member of an immunoglobulin superfamily and possesses a well-conserved putative N-glycosylation site. However, glycosylation is not essential for the function of IZUMO, but has a role in protecting it from fragmentation in cauda epididymis [].
This entry represents a family of proteins predominantly found in Firmicutes, including Uncharacterized protein YpeQ from Bacillus subtilis, It has no known function.
MRPL44 (54S ribosomal protein L44) is a component of the mitochondrial ribosome (mitoribosome), a dedicated translation machinery responsible for the synthesis of mitochondrial genome-encoded proteins, including at least some of the essential transmembrane subunits of the mitochondrial respiratory chain [
].
This entry represents an uncharacterised family of proteins belonging to Mycobacteria. It was previously incorrectly annotated as biofilm regulator BssS (also known as YliH).
Ran-binding protein Vid30/RanBPM/SPLA, SPRY domain
Type:
Domain
Description:
This is the B30.2/SPRY domain found in Ran binding proteins (RanBPs), such as RanBP M homologue (AtRanBPM) from Arabidopsis [
], vacuolar import and degradation protein 30 (Vid30) from Saccharomyces cerevisiae and dual specificity protein kinase splA (SPLA) from Dictyostelium discoideum.The B30.2 domain was first identified as a protein domain encoded by an exon (named B30-2) in the Homo sapiens class I major histocompatibility complex region [
], whereas the SPRY domain was first identified in a Dictyostelium discoideum kinase splA and mammalian calcium-release channels ryanodine receptors []. B30.2 domain consists of PRY and SPRY subdomains. The SPRY domains (after SPla and the RYanodine Receptor) are shorter at the N terminus than the B30.2 domains. The ~200-residue B30.2/SPRY (for B30.2 and/or SPRY) domain is present in a large number of proteins with diverse individual functions in different biological processes. The B30.2/SPRY domain in these proteins is likely to function through protein-protein interaction [].The N-terminal ~60 residues of B30.2/SPRY domains are poorly conserved and, as a consequence, a new domain name PRY was coined for a group of similar sequence segments N-terminal to the SPRY domains [
]. The B30.2/SPRY domain contains three highly conserved motifs (LDP, WEVE and LDYE) []. The B30.2/SPRY domain adopts a highly distorted, compact β-sandwich fold with two additional short β-helices at the N terminus. The β-sandwich of the B30.2/SPRY domain consists of two layers of β-sheets: sheet A composed of eight strands and sheet B composed of seven strands. All the β-strands are in antiparallel arrangement []. The 5th β-strand corresponding to WEVE motif []. Both the N- and C-terminal ends of the B30.2/SPRY domains in general are close to each other [].
This family represents a group of archaeal proteins, including HVO_2753 (also known as Small CPxCG-related zinc finger protein) from Haloferax volcanii [
]. NMR 3D structure analysis revealed the content of four C(P)XCG motifs, suggesting the presence of two zinc-binding pockets. However, only C(P)XCG motifs 2 and 4 (comprising Cys-32 to Cys-35 and Cys-50 to Cys-53) form a zinc binding pocket and binds one zinc atom, while C(P)XCG motifs 1 and 3 (comprising Cys-12 to Cys-15 and Cys-39 to Cys-42) form a four-Cys cluster that do not bind zinc. The four C(P)XCG motifs are critical for protein stability, folding and functionality [].
This entry represents PR-domain zinc finger protein PRDM5, which is a sequence-specific DNA-binding transcription factor that targets hematopoiesis-associated protein-coding and microRNA genes [
]. This entry also includes some related zinc finger proteins from animals.
PRDM4 may function as a transcription factor that recruits protein arginine methyltransferase 5 (PRMT5) to mediate histone arginine methylation and control neural stem cell proliferation and differentiation [
].
This entry represents the C-terminal substrate-domain of LysR-type transcriptional regulator NocR, which is involved in the catabolism of opines. Opines, such as octopine and nopaline, are low molecular weight compounds found in plant crown gall tumours that are produced by the parasitic bacterium Agrobacterium. There are at least 30 different opines identified so far. Opines are utilized by tumor-colonizing bacteria as a source of carbon, nitrogen, and energy. NocR positively regulates the catabolism of nopaline. Both nopaline and octopalin are arginine derivatives. In Agrobacterium tumefaciens, NocR regulates expression of the divergently transcribed nocB and nocR genes of the nopaline catabolism (noc) region [
,
]. This substrate-binding domain shows significant homology to the type 2 periplasmic binding proteins (PBP2).The PBP2 are responsible for the uptake of a variety of substrates such as phosphate, sulfate, polysaccharides, lysine/arginine/ornithine, and histidine. The PBP2 bind their ligand in the cleft between these domains in a manner resembling a Venus flytrap. After binding their specific ligand with high affinity, they can interact with a cognate membrane transport complex comprised of two integral membrane domains and two cytoplasmically located ATPase domains. This interaction triggers the ligand translocation across the cytoplasmic membrane energized by ATP hydrolysis. Besides transport proteins, the PBP2 superfamily includes the substrate- binding domains from ionotropic glutamate receptors, LysR-like transcriptional regulators, and unorthodox sensor proteins involved in signal transduction [
,
,
].
This family consists of uncharacterised proteins from Borrelia species. There is some evidence to suggest that the proteins may be outer surface proteins.
PLASTID TRANSCRIPTIONALLY ACTIVE protein 6 (PTAC6) plays an important part in plastid gene expression [
,
]. It is an essential subunit of the PEP (plastid-encoded RNA polymerase) complex. MTERF5 interacts with PTAC6, and thereby recruits the PEP complex to the transcriptionally paused region of psbEFLJ (a gene that encodes four key subunits of photosystem II) []. PTAC6 also promotes leaf greening [].
Thioredoxin-like fold domain-containing protein MRL7/MRL7L
Type:
Family
Description:
This family represents a group of plant thioredoxin-like fold domain-containing proteins, including MRL7 (Protein MESOPHYLL-CELL RNAI LIBRARY LINE 7, also known as Protein EARLY CHLOROPLAST BIOGENESIS 1 (ECB1) or Protein SUPPRESSOR OF VARIEGATION 4 SVR4) and its paralog MRL7L from Arabidopsis. These proteins are required for early chloroplast development and involved in the regulation of plastid gene expression [
,
,
,
,
]. They also mediate the degradation of two repressors of chloroplast biogenesis, PIF1 and PIF3 in nucleus []. MRL7L is a necessary component of phytochrome signalling for photosynthesis-associated plastid-encoded genes (PhAPGs) activation [].
This entry represents a group of eukaryotic proteins that are typically between 78 and 121 amino acids in length. Proteins in this entry includes human Cilia- and flagella-associated protein 141 (CFAP141, also known as C1orf189 protein). Members of this family may be microtubule inner proteins (MIP) part of the dynein-decorated doublet microtubules (DMTs) in cilia axoneme, which is required for motile cilia beating [
].
GOLIM4 (Golgi integral membrane protein 4), also known as GPP130, is a cycling Golgi membrane protein [
]. It serves as an endosome-to-Golgi trafficking receptor for the toxin [].
Ankyrin repeat domain-containing protein 53 (ANKRD53) is recruited to the mitotic spindle by DDA3 and acts as a regulator of spindle dynamics and cytokinesis [
].
TAC1 (tiller angle control 1) is involved in the regulation of inflorescence branch growth angle [
]. TAC1 belongs to a family known as IGT due to its universally conserved motif (GL(A/T)IGT) present in domain II of all sequences identified [].
This entry represents a group of eukaryotic proteins that are typically between 256 and 320 amino acids in length. There is a single completely conserved residue, phenylalanine (F), that may be functionally important.
Programmed cell death protein 1 (PDCD1), also known as PD1, is an immune-checkpoint receptor mainly expressed by T cells that negatively regulates immune response [
]. It interacts with its ligands PD-L1 and PD-L2 to inhibit T cell effector functions in an antigen-specific manner []. The PD1-mediated inhibitory pathway is exploited by some tumours to attenuate anti-tumour immunity and escape destruction by the immune system [].
This entry represents the C-terminal domain of the putative Leucine Rich Repeat Containing protein 37A or protein 37B (LRRC37A/B) found in eukaryotes. The Leucine Rich Repeats (LRR) lies in the central region. The gene that encodes this protein is found in the chromosomal position 17q11.2, and its microdeletion results in the disease, neurofibromatosis type-1 (NF1) [
]. The function of the protein, LRRC37B is unknown, however experimental data shows expression in the aorta, heart, skeletal muscle, liver and brain during gestation [].
The function of nuclear protein Sp140 is not known, though it contains several chromatin related modules such as plant homeodomain (PHD), bromodomain (BRD) and SAND domain, which suggests a role in chromatin-mediated regulation of gene expression [
]. It also harbours a nuclear localisation signal and a dimerisation domain (HSR or CARD domain). The PHD finger of Sp140 presents an atypical fold which does not bind to histone H3 tails but binds to peptidylprolyl isomerase Pin1. Pin1 catalyses the isomerisation of a phospho-Threonine-Proline bond in Sp140-PHD and thus may modulate Sp140 function [].Human Sp140 is an interferon inducible nuclear leukocyte-specific protein that may be involved in the pathogenesis of acute promyelocytic leukemia and viral infection [
]. It localises to LYSP100-associated nuclear dots and is also a component of the promyelocytic leukemia nuclear body (PML-NBs) [,
]. The Sp140 locus has been identified as a lymphocytic leukemia (CLL) risk locus []. This entry also includes protein Sp140-like (SP140L) which acts as an autoantigen in primary biliary cirrhosis patients [].
