Members of this family occur in Mycoplasma mycoides and two species of Spiroplasma. The protein is small and hydrophobic with two predicted transmembrane (TM) regions.
Hercynine is the betaine (trimethylated amino group) form of histidine. It is the precursor of ergothioneine, a thiourea derivative containing a sulfur atom in the imidazole ring. This small protein occurs in a conserved four-gene cyanobacterial cassette along with an EgtD, the methyltransferase that converts histidine to hercynine as in ergothioneine biosynthesis, and an EgtB homologue, likely to attach some thiol through its sulfur to the hercynine imidazole ring.
This model describes bacterial flagellar biogenesis protein fliP, which is one of the genes within the motility locus on the bacterial chromosome that is involved in structure and function of bacterial flagellum. It was demonstrated that mutants in fliP locus were non-flagellated and non-motile, while revertants were flagellated and motile. In Escherichia coli and related proteins the fliP protein probably [] plays a role in the transport of flagellar proteins. FliP is a protein of about 30 Kd which contains three or four transmembrane regions. Proteins evolutionary related to fliP have been found in a wide range of bacteria (mopC, hrcR, hrpW, spaP, yscR, etc.) and are involved in a variety of signal-peptide independent secretion systems.
Forkhead box protein M1 (FOXM1) is a forkhead transcription factor that regulates expression of cell cycle genes essential for DNA replication and mitosis during organ repair and cancer progression [
]. It is regulated by the mitotic kinase Polo-like kinase 1 (Plk1) []. It binds promoter regions with a preference for tandem repeats of a consensus 'TAAACA' recognition sequence [].
This entry includes human endonuclease III-like protein 1 (NTH1) and its homologues from animals, yeasts and plants. NTH1 is a bifunctional DNA N-glycosylase with associated apurinic/apyrimidinic (AP) lyase function that catalyses the first step in base excision repair (BER), the primary pathway for the repair of oxidative DNA damage [
]. In budding yeasts it is also known as Ntg1, which has an a paralogue, Ntg2 []. Yeast Ntg1 creates a double-strand break at mtDNA origins that stimulates replication in response to oxidative stress [].
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 [,
].This entry represents the 30S ribosomal protein S3Ae from Archaea.
Members of this family are acidic surface proteins with an N-terminal signal peptide and a variant C-terminal sortase recognition sequence, LPXTA rather than LPXTG. The N-terminal region past the signal peptide is repeated a second or third time in many members of this family. Members occur in Firmicutes, encoded next to a dedicated sortase related to SrtC that assembles pilins, suggesting that this protein serves a structural rather than enzymatic role. Processing by the neighbouring sortase may result in polymerisation as well as surface attachment.
Members of this family are proteins of unknown function, about 400 amino acids in length. Members are universal among the Myxococcales (a branch of the Deltaproteobacteria) and occur sporadically elsewhere.
Members of this family are small proteins that appear to be restricted to and yet universal in the Myxococcales. The function is unknown. Members include two tandem loci in Myxococcus xanthus DK 1622, MXAN_4361 and MXAN_4362, although members are not in tandem in other Myxococcales.
This entry represents a 27 residue domain containing features such as: 1) a short Gly/Ser-rich region that ends in an invariant Gly-Cys motif, 2) a highly hydrophobic probable transmembrane alpha helix with a nearly invariant Pro near the end, and 3) a cluster of basic residues (Arg, Lys), and then the end of the protein. This domain occurs only in species of Synergistetes. It closely resembles the MXYO-CTERM domain of the Myxococcales, a division of the Deltaproteobacteria (
). However, MXYO-CTERM domain lacks the the conserved Pro, frequently has two Cys residues instead of one, and most importantly, has a spacer region separating the Gly-Cys motif from the transmembrane segment. As with MYXO-CTERM, the enzyme presumed to recognise and cleave the sorting signal is not known. The lack of a spacer region between motif and TM segment suggests the presumed protease is located largely within the membrane, like rhombosortase and archaeosortase, rather than merely tethered to it like sortase.
Calcium-binding protein CAB45 contains EF-hand domains and may regulate calcium-dependent activities in the endoplasmic reticulum lumen or post-ER compartment [
,
].This entry represents the EF-hand, calcium binding motif of CAB45.
T cell-dependent immune processes require cell-surface interactions that
mediate the initiation, modulation and the ultimate course of the response.The specificity of T cell recognition is determined by the engagement of the
T cell receptor (TCR) on T cells with cognate peptide-MHC complexes presented by antigen presenting cells (APCs). Additional signals are
required to sustain and enhance T cell activity, the most important of whichis provided by the engagement of CD28 on T cells with its ligands B7-1
(CD80) and B7-2 (CD86). By contrast, the interaction of B7 isoformswith cytotoxic T lymphocyte-associated molecule-4 CTLA-4, a CD28 homologue
receptor on T cells (31% identity), provides inhibitory signals requiredfor down-regulation of the response, while it may also prevent T cell
activation by weak TCR signals[
,
,
,
,
].Sequence comparison between human CTLA-4 and CD28 proteins suggests they are
homologous, with the highest of degree of similarity being in the juxta-
membrane and cytoplasmic regions. In addition, the cytoplasmic domainsof human and murine CTLA-4 are identical, suggesting that this region has
important functional properties [].
Proteins in this family contain a DEP domain, which is a globular domain of about 80 residues. This entry includes GTPase-activating proteins (GAPs), such as Iml1 from fungi and GATOR complex protein DEPDC5 from mammals. In Saccharomyces cerevisiae, Iml1 is a GAP subunit of both the SEA (Seh1-associated) and Iml1 complexes (Iml1-Npr2-Npr3). SEA complex is associates dynamically with the vacuole and is involved in autophagy [
,
,
]. Iml1 complex is required for non-nitrogen-starvation (NNS)-induced autophagy []. In mammals, DEPDC5 is a component of the GATOR1 complex functions as an inhibitor of the amino acid-sensing branch of the TORC1 pathway [,
].
This entry represents a group of ACT domain-containing proteins mostly from plants, including ACR1-12 from Arabidopsis. The ACT domains s a regulatory domain that serve as amino acid-binding sites in some feedback-regulated amino acid metabolic enzymes. Plant ACR domain-containing proteins may function as novel regulatory or sensor proteins [
,
].
The function of SZRD1 is not clear. It may act as a tumour suppressor in cervical cancer [
]. Homologues are found in metazoa and fungi. Homologues contain a SUZ domain, which is a conserved RNA-binding domain enriched in positively charged amino acids and first characterised in the Caenorhabditis elegans protein SZY-20 where it has been shown to bind RNA and allow their localization to the centrosome [].
This entry includes ARHGAP11A and ARHGAP11B from humans. ARHGAP11B gene arose from partial duplication of ARHGAP11A (which encodes a Rho guanosine triphosphatase-activating protein) on the human lineage after separation from the chimpanzee lineage [
]. A lack of 55 nucleotides in ARHGAP11B mRNA leads to loss of RhoGAP activity by GAP domain truncation and addition of a human-specific C-terminal amino acid sequence []. ARHGAP11B promotes basal progenitor amplification and is implicated in neocortex expansion [].
The expression of Sushi domain-containing protein 6 (SUSD6), also known as DRAGO or KIAA0247, is regulated by p53 and may cooperate with p53 as oncosuppressor [
]. It has been shown to inhibit growth, migration, invasion of non-small-cell lung cancer through regulating the Notch pathway [] and work as a tumor suppressor in glioma [].
This entry represents a group of FAS1 domain-containing proteins, including Mug57 from S. pombe and YDR262W from S. cerevisiae. Mug57 is a meiotically
upregulated gene (mug) that may have a role in sporulation [].
This entry represents a group of integral membrane proteins of the nuclear envelope (NE), including Brl1 and Brr6 from budding yeasts [
,
]. Brl1 and Brr6 form a complex with Apq12. This complex plays an important role in membrane homeostasis regulation and nuclear pore complex biogenesis [,
].
Members of this protein family are small (typically less than 50 amino acids in length), with the first half highly hydrophobic like transmembrane alpha helices and containing a nearly invariant tyrosine residue. Members from the Desulfovibrionales appear in the position of ccmD of system I c-type cytochrome biogenesis operons (
). This family and ccmD appear very similar in sequence properties, but the very low level of actual sequence identify makes it unclear that the similarity reflects homology per se [
].
Members of this rare family are small, highly hydrophobic, and restricted so far to the genus Mycoplasma, where it appears not to be essential. All members have three hydrophobic transmembrane helical segments.
Members of this family are proteins of unknown function, about 620 amino acids in length, and universal in but restricted to the Myxococcales, an order within the Deltaproteobacteria.
Members of this family are restricted so far to the lineage Leptospira, where they may be the longest protein encoded by the genome. Two or three paralogues are often found. Sequences have significant length variability, with an intein feature most full-length members of this family share. Oddly, members closely related in sequence up to the start of the intein (
) usually show very little sequence similarity C-terminal to the end of the intein (
).
Ectodysplasin-A receptor-associated adapter protein
Type:
Family
Description:
EDARADD is a death domain-containing adaptor molecule for ectodysplasin-A receptor [
]. Mutations of the EDARADD gene has been linked to hypohidrotic ectodermal dysplasia (HED), a rare disorder characterised by deficient development of structures derived from the ectoderm including hair, nails, eccrine glands, and teeth [,
]. Homologues are known only from chordates.
RcsA is a component of the Rcs phosphorelay signaling system. Pathways regulated by the Rcs system include maintenance of cell wall integrity, cell division, motility, and virulence. The pathway involves a histidine kinase (RcsC), a response regulator (RcsB), a phospho-transfer protein (RcsD), a signal transductor (RcsF) and the auxiliary activator protein (RcsA) [
,
]. The response regulator RcsB associates with an unstable protein RcsA to bind to an RcsAB box in the promoter region of several genes, though not all genes require RcsA [,
]. RcsA and RcsB regulate the polysialic and colanic acids metabolism in Escherichia coli [].
RcsB, together with RcsC and RcsD, is a component of the Rcs signaling system. RcsC functions as a membrane-associated protein kinase that phosphorylates RcsD in response to environmental signals. The phosphoryl group is then transferred to the response regulator RcsB, which binds to regulatory DNA regions. RcsB can function as a homodimer or form a heterodimer with the auxiliary activator RcsA [
]. The system regulates expression of numerous genes, including genes involved in colanic acid capsule synthesis, biofilm formation, and growth [,
,
]. It is also involved, with GadE, in controlling glutamate-dependent acid resistance [] and, with BglJ, in derepression of the cryptic bgl operon [].
Lipopolysaccharide assembly protein B (LapB), together with LapA, is involved in assembling lipopolysaccharide [
]. E. coli LapB, also known as YciM, has been shown to act by altering LpxC, an enzyme that catalyses the first committed step of lipid A biosynthesis [].
Proteins in this entry contain a DTW domain (with the presence of a central DTXW motif). DTW domain containing protein may have a SAM-dependent acp transferase activity [
]. This entry includes DTWD2, also known as tRNA-uridine aminocarboxypropyltransferase 2, from humans, DTWD2A from Arabidopsis [] and TAPT (also known as YfiP) from Escherichia coli. TAPT is a tRNA-uridine aminocarboxypropyltransferase that catalyses the formation of 3-(3-amino-3-carboxypropyl)uridine (acp3U) at position 47 of tRNAs [,
].
This entry represents a group of plant proteins, including DIR1 (At5g48485) from Arabidopsis. AtDIR1 is an acidic lipid transfer protein essential for systemic acquired resistance (SAR), which is a defence mechanism that induces protection against a wide range of pathogens in distant, pathogen-free parts of plants after a primary inoculation [
]. Upon SAR induction, DIR1 moves from locally infected to distant uninfected leaves to activate defense priming [].
This entry represents tellurite resistance protein TehA. TehA belongs to the C4-dicarboxylate transporter/malic acid transport (TDT) protein family and is a homologue of plant Slow Anion Channel-Associated 1 (SLAC1) [
]. The tehA gene encodes an integral membrane protein that has been shown to have efflux activity on quaternary ammonium compounds. TehA protein of Escherichia coli functions as a tellurite-resistance uptake permease [,
].
This entry contains uncharacterized oxidoreductase-like domain-containing proteins including mammalian oxidoreductase-like domain-containing protein 1 (OXLD1), and the mitochondrial proteins P31B10.02 and YPL107W from the yeasts
Schizosaccharomyces pombeand
Saccharomyces cerevisiae.
This entry includes the uncharacterized zinc finger protein 511 (ZNF511) which contains C2H2-type zinc fingers. The gene for a homologue from the fruit fly
Drosophila melanogaster, known as protein lethal(2)k10201, is vital and a component of the wunen locus which guides migrating germ cells from the lumen of the developing gut towards the overlying mesoderm [
].
The protozoan parasite that causes Chagas' disease, Trypanosoma cruzi, contains a 24kDa protein that is recognised by antisera from both humans and
experimental animals infected with this organism. Near its C terminus are two regions that have sequence similarity with E-F hand Ca
2+-binding
proteins []. Indeed, the native trypanosome protein exhibits low Ca2+-binding capacity and high Ca
2+-binding affinity, consistent with binding
via E-F hand structures. Immunofluorescence assays have suggested that theprotein is localised to the trypanosome's flagellum. This observation,
coupled with the protein's Ca2+-binding properties, suggests that it may
participate in molecular processes associated with the high motility of the parasite [
]. A set of similar 24kDa proteins, termed calflagins, are contained within
the flagellum of Trypanosoma brucei. These contain three EF-hand Ca2+-
binding domains and one degenerate EF-hand motif [].
Leucine-rich repeat-containing protein 25 (LRRC25) is an inhibitor of signalling pathways. In the RLR-mediated type I interferon signaling pathway, LRRC25 targets DDX58/RIG-I for autophagic degradation [
]. Similarly, the NF-kappa-B signaling pathway and the inflammatory response are inhibited by targeting p65/RELA for degradation []. LRRC25 is a type I transmembrane protein with an N-terminal lumenal domain, a single transmembrane domain and a larger cytoplasmic domain. The leucine-rich repeats are in the N-terminal, lumenal domain.
Vesicle-associated membrane protein 4 (VAMP4) is required to maintain the ribbon structure of the Golgi apparatus [
]. It is essential for activity-dependent bulk endocytosis (ADBE) [].
Adherens junction-associated protein 1 (AJAP1, also known as shrew-1) was first discovered as a transmembrane protein of adherent junctions in epithelial cells. Later, it was found to act as a tumour suppressor in gliomas. It may affect cell motility, migration, invasion and proliferation [
,
]. Homologues are found only in chordates.
This entry includes the uncharacterized zinc finger proteins, including ZNF277 from human and C19B12.07c from the fission yeast Schizosaccharomyces pombe. ZNF277 contains a C2H2-type 1 and a C2H2-type 2 zinc finger whereas C19B12.07c contains a single C2H2-type zinc finger.
This entry represents a group of Cdc42-binding proteins known as SPECs (for small protein effector of Cdc42), including SPEC1 and SPEC2 from humans. SPECs modulate the activity of the Rho GTPase Cdc42, which plays important roles in actin polymerization and kinase signaling [
]. SPEC1 and SPEC2 play a role in F-actin accumulation in activated T lymphocytes and may play a role in early contractile events in phagocytosis [].
This entry includes proteins containing an N-terminal tripartite DENN domain, including DENND1A (also known as connecdenn 1), DENND1B (connecdenn 2) and DENND1C (connecdenn 3). These proteins act as guanine-nucleotide exchange factors for Rab35 through the DENN domain. Inactive GDP-bound RAB35 is converted into its active GTP-bound form by the exchange of GDP to GTP. The DENN domains of DENND1A and DENND1B, but not DENND1C, bind Rab35, indicating that binding and activation are separate. The C-termini of DENND1A, DENND1B and DENND1C differ significantly, but each binds to clathrin and to the clathrin adaptor AP-2. This is a means to regulate clathrin-mediated endocytosis of synaptic vesicles and exit from early endosomes [
].
SCHIP-1 is a coiled-coil protein that specifically associates with schwannomin in vitro and in vivo. The product of the neurofibromatosis type 2 (NF2) tumour suppressor gene, known as schwannomin or merlin, is involved in NF2-associated and sporadic schwannomas and meningiomas. It is closely related to the ezrin-radixin-moesin family members, which link membrane proteins to the cytoskeleton. Association with SCHIP-1 can be observed only with some naturally occurring mutants of schwannomin, or a schwannomin spliced isoform lacking exons 2 and 3, but not with the schwannomin isoform exhibiting growth-suppressive activity [
].This entry also includes IQ motif containing J-Schwannomin-Interacting Protein 1 (IQCJ-SCHIP-1), an isoform of the SCHIP-1. IQCJ-SCHIP-1 is a multipartner ankyrin- and spectrin-binding protein involved in the organization of nodes of ranvier [
].
The entry represents proteins with various designations in the seadornavirus group: VP9 in Banna virus, VP10 in Liao ning virus, and VP11 in Kadipiro virus. VP9 is a spike-forming protein that mediates virion attachment to the host cell receptors and plays a major role in cell penetration [
].
WW domain-binding protein 4 (WBP4; also known as formin-binding protein 21) is a component of the spliceosome, which is involved in pre-mRNA splicing [
]. It contains a matrin-type zinc finger and two tandem WW domains. It interacts with the splicing factor SIPP1, and its binding and activation of pre-mRNA splicing depend on the WW domains []. This entry also includes zinc finger protein ZOP1 from Arabidopsis thaliana, which is also a pre-mRNA splicing factor that associates with several typical components of the splicing machinery and promotes Pol IV-dependent siRNA accumulation, DNA methylation, and transcriptional silencing [].
This entry represents a group of proteins that contain at least two copies of a C2H2-type zinc finger, including cytoplasmic 60S subunit biogenesis factor ZNF622 from animals [
], Reh1 and Rei1 from budding yeasts, and core trichothecene cluster protein 15 (TRI15) from Fusarium.Cytoplasmic 60S subunit biogenesis factor ZNF622, Reh1 and Rei1 are involved in maturation of the large (60S) ribosomal subunit. Rei1 is required for re-importing the 60S subunit export factor Arx1 from the cytoplasm to the nucleus, and both Reh1 and Rei1 are required for cytoplasmic maturation of the 60S subunit, that the two proteins have redundant functions, but without both the 60S subunit is labile to salt [
].TRI15 is a component in the biosynthesis of trichothecene mycotoxins, although its role is unknown [
].
The flagellar hook-associated protein 2 (HAP2 or FliD) forms the distal end of the flagella, and plays a role in mucin specific adhesion of the bacteria [
].
The function of leucine-rich repeat-containing protein 56 (LRRC56) from vertebrates is not clear. However, its homologue in Chlamydomonas, also known as ODA8, is a conserved flagellar protein with a role in formation and transport of mature dynein complexes during flagellar assembly [
]. LRRC56 from Trypanosoma brucei brucei is required for the assembly of dynein arms in the distal portion of flagellum axoneme [].
WD40-repeat 47, also known as Nemitin, is a microtubule-associated protein that
is essential for brain development. It is involved in microtubule dynamics and regulation of autophagic flux for axonal outgrowth and guidance [,
].
The function of WD40-repeat (WDR)-containing proteins, one of the largest eukaryotic protein families, is largely unknown. This family represents WDR31.
The MPA1 proteins function in capsule polysaccharide and exopolysaccharide polymerisation and/or export. They possess a characteristic carboxy-terminal ATP-binding domain and one or more regions which can form coiled-coils and are located in the periplasmic domain between the two transmembrane regions of the protein [
].This entry also includes some capsular polysaccharide biosynthesis proteins from the CpsC/CapA family, including CpsC from Streptococcus pneumoniae. CpsC is required for CpsD phosphorylation and is involved in the regulation of capsular polysaccharide biosynthesis. It may be part of a complex that directs the coordinated polymerisation and export to the cell surface of the capsular polysaccharide [
].
This group of proteins are part of a large genetic locus which is associated with exopolysaccharide (EPS) biosynthesis [
,
]. This entry includes ExoP from Rhizobium meliloti and PssP from Rhizobium leguminosarum bv. trifolii. They belong to the PCP2a family involved in the synthesis of high-molecular-weight EPS []. They contain a periplasmic domain flanked by two transmembrane regions and an additional cytoplasmic domain. ExoP is involved in polymerization and secretion of succinoglycan. Mutations in the Walker A ATP-binding motif found in the cytoplasmic domain of ExoP prevented ATPase activity of the ExoP protein [].
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 [,
].This entry represents the archaeal ribosomal protein S2 family.
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 [,
].Ribosomal protein S3 is one of the proteins from the small ribosomal subunit. This family describes ribosomal protein S3 of the archaea.
SERTA domain-containing protein 4 (SERTAD4) is highly expressed in adult murine epidermal tissues and in digits. The function of the SERTA domain is unknown, but proteins containing this domain have been linked to cell cycle progression and chromatin remodelling. SERTAD4 resides predominantly in the nucleus throughout all stages of the cell cycle [
].
This small protein has a very limited distribution, being found so far only among some gamma-Proteobacteria. The member from Escherichia coli was shown to bind selenium in the absence of a working SelD-dependent selenium incorporation system [
]. Note that while the E. coli member contains a single Cys residue, a likely selenium binding site, some other members of this protein family contain two Cys residues or none.
BcsE (bacterial cellulose synthase E) or YhjS, is required for cellulose biosynthesis in Salmonella enteritidis. Its role is this process across multiple bacterial species is implied by the partial phylogenetic profiling algorithm. Members are found in the vicinity of other cellulose biosynthesis genes [
,
].BcsE contains the C-terminal GIL domain. The GIL domain, for GGDEF I-site like domain, is a c-di-GMP binding domain on the BcsE proteins of enterobacteria. It is not essential for cellulose synthesis but is critical for maximal cellulose production. Cellulose production in enterobacteria is controlled by a two-tiered c-di-GMP-dependent system involving BcsE and the PilZ domain containing glycosyltransferase BcsA. The RxGD motif of the GIL domain is required for c-di-GMP binding [
,
,
,
].
Cellulose biosynthesis protein BcsG is a component of bacterial cellulose synthase complex that plays a role in biofilm formation in bacteria [
,
,
]. It is a Zn-dependent phosphoethanolamine transferase that catalyses transfer of phosphoethanolamine residues from membrane phosphatidylethanolamine to the glucosyl residues in the nascent cellulose chain [,
,
,
].
A number of bacteria utilise urea as a nitrogen source by the urea carboxylase/allophanate hydrolase pathway, which uses biotin and consumes ATP, rather than by means of the nickel-dependent enzyme urease [
]. This entry represents one of a pair of homologous, tandem uncharacterised genes found together with the urea carboxylase and allophanate hydrolase genes.
A number of bacteria utilise urea as a nitrogen source by the urea carboxylase/allophanate hydrolase pathway, which uses biotin and consumes ATP, rather than by means of the nickel-dependent enzyme urease [
]. This entry represents one of a pair of homologous, tandem uncharacterised genes found together with the urea carboxylase and allophanate hydrolase genes.
TMX2 contain the TRX domain, an N-terminal signal peptide, a potential transmembrane domain, an Myb DNA-binding domain repeat signature, an endoplasmic reticulum (ER) membrane retention signal (KKXX-like motif), and a dileucine motif in the tail. In TMX2, the TRX domain redox active CXXC motif is replaced with SXXC [
,
]. Homologues are found only in metazoa. It is an ER and mitochondria-associated protein that may function as a regulator of cellular redox state and thereby regulates protein post-translational modification, protein folding and mitochondrial activity. It indirectly regulates neuronal proliferation, migration, and organization in the developing brain [].
RhoG is a GTPase with high sequence similarity to members of the Rac subfamily, including the regions involved in effector recognition and binding. However, RhoG does not bind to known Rac1 and Cdc42 effectors, including proteins containing a Cdc42/Rac interacting binding (CRIB) motif. Instead, RhoG interacts directly with Elmo, an upstream regulator of Rac1, in a GTP-dependent manner and forms a ternary complex with Dock180 to induce activation of Rac1 [
]. The RhoG-Elmo-Dock180 pathway is required for activation of Rac1 and cell spreading mediated by integrin, as well as for neurite outgrowth induced by nerve growth factor. Thus RhoG activates Rac1 through Elmo and Dock180 to control cell morphology []. RhoG has also been shown to play a role in caveolar trafficking [] and has a novel role in signaling the neutrophil respiratory burst stimulated by G protein-coupled receptor (GPCR) agonists []. Most Rho proteins contain a lipid modification site at the C terminus, with a typical sequence motif CaaX, where a = an aliphatic amino acid and X = any amino acid. Lipid binding is essential for membrane attachment, a key feature of most Rho proteins.
Picornaviruses are single-stranded RNA viruses. Processing of the viral polyprotein by picornains 3C and 2A generates capsid proteins VP0, VP1 and VP3, but VP0 undergoes an autolytic cleavage during virion assembly to generate capsid proteins VP2 and VP4 [
]. The autolytic cleavage was originally thought to be the action of a serine-type peptidase, but from analogy with the similar autoproteolytic cleavages that are known for capsid proteins from nodaviruses (MEROPS peptidase family N1), tetraviruses (MEROPS peptidase family N2), picobirnaviruses (MEROPS peptidase family N5) and reoviruses (MEROPS peptidase family N7), it is more likely that VP0 is an asparagine-type peptidase; autocatalytic cleavage being promoted by cyclization of a conserved asparagine. .
This entry represents the immunoglobulin-binding domain found in the Staphylococcus aureus virulence factor protein A (SpA). Protein A contains five highly homologous Ig-binding domains in tandem (designated domains E, D, A, B and C), which share a common structure consisting of three helices in a closed left-handed twist. Protein A can exist in both secreted and membrane-bound forms, and has two distinct Ig-binding activities: each domain can bind Fc-gamma (the constant region of IgG involved in effector functions) and Fab (the Ig fragment responsible for antigen recognition) [
].
This entry represents the full-length form of ribosomal protein L25, such as ribosomal protein TL5 of Thermus thermophilus. It has homology to the general stress protein Ctc of Bacillus subtilis, which has now been localised to ribosomes and can be viewed as the long form, or Ctc form, of L25 [
,
]. Ribosomal protein L25 of Escherichia coli and Haemophilus influenzae appear to be orthologous, but consist only of the N-terminal half of Ctc and TL5. Both short (L25-like) and full-length (CTC-like) forms of L15 bind the E-loop of bacterial 5S rRNA.
Chromobox protein homolog 2 (CBX2) is a polycomb protein, responsible for polycomb-repressive complex 1 (PRC1) targeting to chromatin via recognition of the repressive mark H3K27me3 [
]. CBX2 is required during sex determination to stabilize the testis fate by blocking the upregulation of bivalent ovary pathway genes []. It is overexpressed in breast cancer and plays an essential role in tumour progression [,
].
WDR73 (WD repeat-containing protein 73) contains six WD40 repeats that form a six-bladed propeller structure. It is expressed in brain and kidney, localizing to spindle poles during mitosis. Mutations of the WDR73 gene cause Galloway-Mowat syndrome, a rare autosomal-recessive condition characterised by nephrotic syndrome associated with microcephaly and neurological impairment [
,
].
This family includes Zinc finger proteins 800 and 341 from human which contain C2H2-type zinc fingers. The function of ZNF800 is not clear. ZNF341 is a transcriptional activator of STAT3 involved in the regulation of immune homeostasis. It is also able to activate STAT1 transcription [
,
].
Ferric Chelate Reductase 1 Like protein (FRRS1L) interacts with both GluA1 and GluA2 subunits of AMPA receptors (AMPARs). It plays an important role in the regulation of excitatory synaptic strength [
]. Mutations in the FRRS1L gene cause epileptic encephalopathy, early infantile, 37 (EIEE37), a form of epileptic encephalopathy, a heterogeneous group of severe childhood onset epilepsies characterised by refractory seizures, neurodevelopmental impairment, and poor prognosis [,
].
The function of CCDC170 is not clear. It may play a role in Golgi-associated microtubule organization and stabilization [
]. It has been linked to breast cancer []. Homologues are found only in metazoa.
Alpha-TIF (VP16) from Herpes Simplex virus is an essential tegument protein involved in the transcriptional activation of viral immediate early (IE) promoters (alpha genes) during the lytic phase of viral infection. VP16 associates with cellular transcription factors to enhance transcription rates, including the general transcription factor TFIIB and the transcriptional coactivator PC4. The N-terminal residues of VP16 confer specificity for the IE genes, while the C-terminal residues are responsible for transcriptional activation. Within the C-terminal region are two activation regions that can independently and cooperatively activate transcription [
]. VP16 forms a transcriptional regulatory complex with two cellular proteins, the POU-domain transcription factor Oct-1 and the cell-proliferation factor HCF-1 []. VP16 is an alpha/beta protein with an unusual fold. Other transcription factors may have a similar topology.
This entry includes human coiled-coil domain-containing protein 144A/B/C (C144A/B/C). C144A may play a role in preventing the formation of kidney stones through inhibition of calcium oxalate monohydrate (COM) crystallization, attenuating COM-induced apoptotic injury to renal epithelial cells [
]. C144A may also exhibit antilithiatic (preventing the formation of kidney stones) activity through crystal binding, hindering the crystal attachment to renal epithelial cells, a prerequisite to initiate inflammatory response [].
This entry includes Protein phosphatase PTC7 homologue fig from Drosophila, Protein phosphatase PTC7 homologue from human and related proteins. Human PTC7 is a protein phosphatase which positively regulates biosynthesis of the ubiquinone, coenzyme Q [
]. It dephosphorylates the ubiquinone biosynthesis protein COQ7 which is likely to lead to its activation []. The homologue from the fission yeast Schizosaccharomyces pombe is known as 5-azacytidine resistance protein azr1, because it suppresses sensitivity to the C5 DNA methyltransferase inhibitor 5-azacytidine [].
WDR41 is the non-catalytic component of the C9orf72-SMCR8 complex, a complex that has guanine nucleotide exchange factor (GEF) activity and regulates autophagy [
,
,
,
].
STAP1 and STAP2 are signal-transducing adaptor proteins. They contain Pleckstrin Homology (PH) and SH2 domains along with several tyrosine phosphorylation sites.STAP1 functions as a docking protein acting downstream of Tec tyrosine kinase in B cell antigen receptor signaling. It is phosphorylated by Tec and participates in a positive feedback loop, increasing Tec activity [
]. STAP-1 has been shown to interact with STAT5 []. STAP2 is a substrate of breast tumour kinase, an Src-type non-receptor tyrosine kinase that mediates the interactions linking proteins involved in signal transduction pathways [
].
Human CCDC93 is part of the COMMD/CCDC22/CCDC93 (CCC) complex that interacts with the multisubunit WASH complex, which is required for endosomal deposition of F-actin and cargo trafficking in conjunction with the retromer [
]. The CCC complex controls Notch activation by modulating its intracellular trafficking [].
RNF17, also known as Mmip-2, is a RING-finger protein that interacts with all four known Mad proteins, redistributes them to the cytoplasm, and thus enhances c-Myc function [
].
This entry includes a group of animal F-box containing proteins, including FBX25 and FBX32. FBXO32 is a substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins [
]. FBX25 is strongly expressed in human brain [].
TTC19 is involved in complex III biogenesis and the clearance of UQCRFS1 N-terminal fragments [
]. Mutations in the TTC19 gene cause mitochondrial complex III deficiency and neurological impairment in humans and flies [].
Polyadenylate-binding protein-interacting protein 2-like
Type:
Family
Description:
This entry includes Paip2 (also known as Paip2A) and related proteins, such as Paip2B. Paip2 is a transcription repressor that inhibits translation by interdicting PABP (poly(A) binding protein) function [
]. Paip2B acts in a manner similar to Paip2. However, they are expressed in different tissues and cell lines. Also, Paip2 is more highly ubiquitinated than is Paip2B and is degraded more rapidly by the proteasome [].
This regulatory protein is expressed from an immediate early gene in the cell cycle of Herpesviridae. The protein is known by various names including IE-68, US1, ICP22 and IR4. It acts as a general transcriptional regulator of cellular and viral mRNAs, through modifications on the host RNA polymerase II which inhibit host genome transcription, leading to cell cycle deregulation and loss of efficient antiviral response. IE68 also recruits cellular transcription elongation factors to viral genomes for efficient transcription elongation of viral genes [
,
]. In Herpesvirus type-2, this protein functions as a E3 ubiquitin ligase which interacts with STAT1, STAT2, IFN regulatory factor 9 (IRF9), and other ubiquitinated proteins, promoting its degradation and resulting in the blockade of ISG factor 3 (ISGF3) nuclear translocation. Through this mechanism, the production of ISG54 is inhibited and, thus, it inhibits innate immunity response during viral infection [].
This family consists of a envelope glycoprotein GP2a or ORF2 in Porcine reproductive and respiratory syndrome virus (PRRSV) [
]. Also in the family is a minor structural protein from lactate dehydrogenase-elevating virus.
This family of bacterial proteins includes DNA processing protein A (DprA) from Streptococcus pneumoniae and Smf, the Bacillus subtilis orthologue. DprA is a new member of the recombination-mediator protein family, dedicated to natural bacterial transformation [
]. In Helicobacter pylori, DprA is required for natural chromosomal and plasmid transformation []. It has now been shown that DprA binds cooperatively to single-stranded DNA (ssDNA) and interacts with RecA. In the process, DprA-RecA-ssDNA filaments are produced and these filaments catalyse the homology-dependent formation of joint molecules. While the Escherichia coli SSB protein limits access of RecA to ssDNA, DprA alleviates this barrier []. DprA has a role not only in ensuring production of transformants via interaction with RecA, it is also involved in competence shut-off via interaction with ComE [].
This family represents GGAs (Golgi-associated, gamma-adaptin homologous, ARF-interacting proteins) family which includes GGA1, GGA2 and GGA3. They are adaptor proteins that play a role in protein sorting and trafficking between the trans-Golgi network (TGN) and endosomes [
,
]. They mediate the ARF-dependent recruitment of clathrin to the TGN and binds ubiquitinated proteins and membrane cargo molecules with a cytosolic acidic cluster-dileucine (DXXLL) motif [] and they also regulate retrograde transport of phosphorylated form of BACE1 from endosomes to the trans-Golgi network []. These proteins have a multidomain structure consisting of an N-terminal VHS domain linked by a short proline-rich linker to a GAT (GGA and TOM) domain, which is followed by a long flexible linker to the C-terminal appendage, GAE (Gamma-Adaptin Ear) domain [].
MerT is an mercuric transport integral membrane protein and is responsible for transport of the Hg2+ iron from periplasmic MerP (also part of the transport system) to mercuric reductase (MerA) [
,
].
Antifreeze proteins (AFPs) are a class of proteins that are able to bind to and inhibit the growth of macromolecular ice, thereby permitting an organism to survive subzero temperatures by decreasing the probability of ice nucleation in their bodies [
]. These proteins have been characterised from a variety of organisms, including fish, plants, bacteria, fungi and arthropods. This entry represents insect AFPs of the type found in Tenebrio molitor (Yellow mealworm) and in Dendroides canadensis (Pyrochroid beetle).The structure of these AFPs consists of a right-handed β-helix with 12 residues per coil. Each 12 residue-repeat contains two cys residues that form a disulphide bridge. The β-helices of insect AFPs present a highly rigid array of threonine residues and bound water molecules that can effectively mimic the ice lattice. As such, β-helical AFPs provide a more effective coverage of the ice surface compared to the α-helical fish AFPs [
].A second insect antifreeze from Choristoneura fumiferana (Spruce budworm) (
) also consists of β-helices, however in these proteins the helices form a left-handed twist; these proteins show no sequence homology to the current entry, but may act by a similar mechanism. The β-helix motif may be used as an AFP structural motif in non-homologous proteins from other (non-fish) organisms as well.
