This entry represents a group of plant proteins, including VASCULAR-RELATED UNKNOWN PROTEINS 1-4 (VUP1-4) from Arabidopsis. VUP1 may be involved in regulating xylem development by tissue or cell specific modulation of hormone signaling pathways [
].
This entry includes a group of plant F-box proteins, including EID1 and EDL1/2/3 from Arabidopsis. EID1 is part of the SCF (ASK-cullin-F-box) E3 ubiquitin ligase complex [
,
]. It functions as a negative regulator in far-red light signaling downstream of the phyA in Arabidopsis []. The allelic variation of the tomato homologue of the Arabidopsis EID1 has been linked to slower circadian rhythms []. EID1-like protein 3 (EDL3) is involved in the regulation of abscisic acid signalling [].
This protein family was first noted as a paralogous set in Porphyromonas gingivalis, but it is more widely distributed among the Bacteroidetes. The protein family is now renamed GLPGLI after its best-conserved motif.
The YhbY family of proteins are predicted to bind RNA on the basis of structural similarity to known RNA-binding proteins [
]. The Escherichia coli YhbY protein cosediments with free 50S ribosomal subunits, implying a role in ribosome assembly.
Members of this family of proteins, with average length of 210, have no invariant residues but five predicted transmembrane segments. Strangely, most members occur in groups of consecutive paralogous genes. A striking example is a set of eleven encoded consecutively, head-to-tail, in Staphylococcus aureus strain COL.
Mixl1 is a homeobox transcription factor essential for the patterning of axial mesendodermal structures during early embryogenesis [
,
]. It interacts with the T-box protein Brachyury and related members of the T-box family of transcription factors; this interaction negatively regulates Mixl1 transcriptional activity []. In mice, enforced expression of Mixl1 results in transplantable AML (acute myeloid leukemia), suggesting a leukemogenic potential for Mixl [].
Retroviral matrix proteins (or major core proteins) are components of envelope-associated capsids, which line the inner surface of virus envelopes and are associated with viral membranes [
]. Matrix proteins are produced as part of Gag precursor polyproteins. During viral maturation, the Gag polyprotein is cleaved into major structural proteins by the viral protease, yielding the matrix (MA), capsid (CA), nucleocapsid (NC), and some smaller peptides. Gag-derived proteins govern the entire assembly and release of the virus particles, with matrix proteins playing key roles in Gag stability, capsid assembly, transport and budding. Although matrix proteins from different retroviruses appear to perform similar functions and can have similar structural folds which predominantly consist of four closely packed α-helices that are interconnected through loops, their primary sequences can be very different []. This entry represents matrix proteins from beta-retroviruses such as Mason-Pfizer monkey virus (MPMV) (Simian Mason-Pfizer virus) and Mouse mammary tumor virus (MMTV) [
,
,
]. This entry also identifies matrix proteins from several eukaryotic endogenous retroviruses, which arise when one or more copies of the retroviral genome becomes integrated into the host genome [].
Proteins in this entry are part of the iron-mineralizing encapsulin-associated Firmicute (IMEF) system found in encapsulin nanocompartments. Encapsulins are involved in microbial iron storage and redox metabolism [
,
]. The IMEF cargo protein () from Quasibacillus thermotolerans (also known as ferritin-like protein) has been characterised as a ferritin-like iron-binding protein that may play a role in iron mineralization in the encapsulin nanocompartment. It has ferroxidase activity even when encapsulated, the rate is probably controlled by the rate of Fe flux across the nanocompartment pores [
,
].
Members of this protein family are found exclusively in the Cyanobacteria, usually encoded next to a gene encoding cyanoexosortase B (
). This relationship resembles the association of the unrelated protein family
with cyanoexosortase A (
), and of most exosortases with EpsI.
Members of this family share twin CxxC motifs near the C terminus, suggesting a DNA- or RNA-binding activity. The spacing between CxxC motifs is variable, from 11 to 16 amino acids. Members in general occur on plasmids or near other markers of lateral gene transfer (transposases, integrases, endonucleases, etc).
The complete DNA sequence of the genome of Vaccinia virus has been
determined []. 198 "major"protein-coding regions and 65 overlapping
"minor"regions have been identified, with a total of 263 potential genes. The genes are compactly organised along the genome, with few noncoding
regions []. The function of the majority of proteins encoded by these openreading frames is so far undetermined.
The D9 protein contains an evolutionarily conserved MutT domain core,
which is also found in a variety of other viral, prokaryotic and eukaryoticproteins.
This entry represents a group of conserved hypothetical proteins from a narrow range of species. In Clostridium botulinum A ATCC 19397, the gene occurs immediately after a five gene operon for biosynthesis of the natural product bacimethrin, a thiamin antivitamin antibiotic.
This domain is specific to the signalling protein dishevelled. Dishevelled (Dsh/Dvl) is a highly conserved protein family that plays an important role in mediating Wnt signaling. Wnt signal transduction pathways control a variety of developmental and homeostatic events. Dishevelled is involved in both the canonical and non-canonical (B-catenin-independent) pathways [
].This domain is found adjacent to the PDZ domain (
), often in conjunction with DEP (
) and DIX (
).
Members of this family feature an N-terminal signal sequence, small size, and two invariant Cys residues, 10-20 residues apart. One member of this family, UrcA from the aerobic bacterium Caulobacter crescentus, is expressed so highly in response to uranium, but not other heavy metals, that a genetically engineered strain expressing green fluorescent protein in place of UrcA serves as a biodetector for micromolar uranyl ion. Caulobacter crescentus tolerates high levels of UVI exposure by mineralising the uranium. UrcA and its homologues may participate in such a process [
].
This entry represents a group of plant proteins, including LORELEI (LRE) and LORELEI-like proteins (LLG1, LLG2 and LLG3) from Arabidopsis. LORELEI is a female gametophyte-specific component of the signalling pathway required for fertilization [
,
,
]. LLG1/LRE act as a chaperone and co-receptor for receptor kinase FERONIA, which is a multifunctional regulator for plant growth and reproduction [].
Alpha-haemoglobin stabilising protein (AHSP) acts a molecular chaperone for free alpha-haemoglobin, preventing the harmful aggregation of alpha-haemoglobin during normal erythroid cell development: it specifically protects free alpha-haemoglobin from precipitation. AHSP adopts a helical secondary structure consisting of an elongated antiparallel three α-helix bundle [
].
Trichohyalin-like protein 1 (TCHHL1) is a member of the fused-type S100 protein family. It contains an N-terminal E-hand domain, one trans-membrane domain and a nuclear localization signal. Its function is not clear. It is expressed in the basal layer of the normal epidermis and may be associated with the proliferation of keratinocytes [
].The fused-type S100 protein family is a group of calcium binding S100-related proteins. The 'fused' gene family includes multifunctional epidermal differentiation proteins - profilaggrin, trichohyalin, repetin [
], hornerin, and cornulin; functionally these proteins are associated with keratin intermediate filaments and partially crosslinked to the cell envelope. These 'fused' gene proteins contain N-terminal sequence with two Ca-binding EF-hands motif, which may be associated with calcium signalling in epidermal cells and autoprocessing in a calcium-dependent manner. In contrast to S100 proteins, 'fused' gene family proteins contain an extraordinary high number of almost perfect peptide repeats with regular array of polar and charged residues similar to many known cell envelope proteins [].
This entry includes the eukaryotic L30 subunit, the archaeal L7 subunit and the ribosome biogenesis protein RLP7 (ribosomal protein L7-like) from yeasts. RLP7 is required for the biogenesis of the 60S ribosomal subunit [
].Ribosomal protein L30 is one of the proteins from the large ribosomal subunit. L30 belongs to a family of ribosomal proteins which, on the basis of sequence similarities [
], groups bacteria and archaea L30, yeast mitochondrial L33, and Drosophila melanogaster, Dictyostelium discoideum (Slime mold), fungal and mammalian L7 ribosomal proteins. L30 from bacteria are small proteins of about 60 residues, those from archaea are proteins of about 150 residues, and eukaryotic L7 are proteins of about 250 to 270 residues.
Ataxin-7-like protein 3B (ATXN7L3B) interacts with ENY2, a SAGA component. It regulates histone H2Bub1 levels and SAGA deubiquitinase activity through competition for ENY2 binding [
]. It has been linked to neurodegenerative disease [].
Members of this family are FemA/FemB family proteins from a cassette that some Leptospira have in their O-antigen biosynthesis regions and share with a cassette from gamma proteobacterium IMCC1989.
This short repeat is found in multiple copies in bacterial M proteins. The M proteins bind to IgA and are closely associated with virulence.
The M protein has been postulated to be a major group A streptococcal (GAS) virulence factor because of its contribution to the bacterial resistance to opsonophagocytosis [].
Members of this family, including MG_281 of Mycoplasma genitalium, bind conserved regions of the IgG light chain sequences, blocking IgG's normal function of antigen-specific binding. They are therefore important virulence proteins. Proteins in this entry contain a domain (
) shared by many other Mycoplasma and Ureaplasma proteins [
].
Members of this family are uncharacterised proteins from the genus Mycoplasma, typically about 260 amino acids long, with a hydrophobic predicted transmembrane alpha helix toward each end. Often two family members are encoded in tandem, e.g. MG_279 and MG_280 from Mycoplasma genitalium.
The adenovirus terminal protein precursor or preterminal protein (pTP) functions as a primer for the initiation of virus DNA replication. It forms a heterodimer with Ad DNA polymerase (pol) [
,
]. pTP is processed at two sites by the virus-encoded protease to yield mature terminal protein (TP) via an intermediate (iTP) [].
This family includes Beta-catenin-interacting protein 1 (CTNNBIP1, also known as ICAT) and protein LZIC from chordates. CTNNBIP1 is a suppressor of the Wnt/beta-catenin signaling pathway. It negatively regulates beta-catenin co-transcriptional activity by competing with TCF/LEF factors in their binding to beta-catenin superhelical core [
,
,
].Protein LZIC contains a leucine zipper domain and an ICAT homologous domain, with particular conservation of residues that are used by ICAT for beta-catenin-binding [
,
].
This entry represents a group of proteins mostly from Cyanobacteria (blue-green algae) and plants, including TRIGALACTOSYLDIACYLGLYCEROL 2 (TGD2) from Arabidopsis. TGD2 is a component of a phosphatidic acid/lipid transport complex in the chloroplast envelope [
]. Proteins in this entry contain a Mce/MlaD domain.
This entry represents a group of proteins mostly from plants and Cyanobacteria (blue-green algae), including protein NEOXANTHIN-DEFICIENT 1 (NDX1) from tomato. NDX1 is involved in neoxanthin biosynthesis [
].
Proteins in this family contain SH3 and fibronectin type III (FN3) domains, with the FN3 domains inserted within the SH3 domains. Members include peripheral-type benzodiazepine receptor-associated protein 1 (PRAX-1, TSPOAP1 or RIMBP1, also known as RIMS-binding protein 1 or TSPO-associated protein 1) and RIMS-binding protein 2 (RIMBP2). PRAX-1 interacts with the peripheral benzodiazepine receptor [
]. RIMBP2 interacts with subunits of the voltage-gated Ca(2+) channels [].RIMs binding proteins (RBPs, RIM-BPs) associate with calcium channels present in photoreceptors, neurons, and hair cells; they interact simultaneously with specific calcium channel subunits, and active zone proteins, RIM1 and RIM2 [
]. RIMs are part of the matrix at the presynaptic active zone and are associated with synaptic vesicles through their interaction with the small GTPase Rab3 []. RIM-BPs play a role in regulating synaptic transmission by serving as adaptors and linking calcium channels with the synaptic vesicle release machinery []. RIM-BPs contain three SH3 domains and two to three fibronectin III repeats. Invertebrates contain one, while vertebrates contain at least two RIM-BPs, RIM-BP1 and RIM-BP2. RIM-BP1 is also called peripheral-type benzodiazapine receptor associated protein 1 (PRAX-1). Mammals contain a third protein, RIM-BP3 []. RIM-BP1 and RIM-BP2 are predominantly expressed in the brain where they display overlapping but distinct expression patterns, while RIM-BP3 is almost exclusively expressed in the testis and is essential in spermiogenesis []. The SH3 domains of RIM-BPs bind to the PxxP motifs of RIM1, RIM2, and L-type (alpha1D) and N-type (alpha1B) calcium channel subunits [].
NOBOX is an oocyte-specific transcription factor essential for folliculogenesis and expression of many germ cell-specific genes in mice [
]. It regulates the expression of Pad6, a peptidylarginine deiminase in the oocyte []. It has also been shown to function in regulation of embryonic genome activation, pluripotency gene expression, and blastocyst cell allocation in cattle []. Mutations of the NOBOX gene have been linked to primary ovarian insufficiency [,
,
].
GBX-1 and GBX-2 are homeobox proteins. The role of the mouse GBX-2 in defining the mid/hindbrain organiser has been studied extensively, but little is known about GBX-1. GBX-1 is expressed first during gastrulation and later in a dynamic pattern in the central nervous system [
].Homeobox protein unplugged (unpg) from Drosophila plays a regulatory role in neural branching of the tracheae [
]. Like vertebrate orthologue Gbx2, unplugged may also have a role in brain development. Studies indicate that Drosophila brain displays developmental genetic features similar to those observed for the midbrain/hindbrain boundary region in vertebrates [].The homeobox domain (homeodomain) is a 60-residue motif first identified in a number of Drosophila homeotic and segmentation proteins, but now known to be well-conserved in many other animals, including vertebrates [
,
]. Proteins containing homeobox domains are likely to play an important role in development - most are known to be sequence-specific DNA-binding transcription factors. The domain binds DNA through a helix-turn-helix (HTH) structure.
Proteins in this family contain a TROVE (Telomerase, Ro and Vault) domain and include RNA-binding protein RO60 (TROVE2), an RNA-binding protein that binds to misfolded non-coding RNAs, pre-5S rRNA, and several small cytoplasmic RNA molecules known as Y RNAs [
,
].
This entry represents a group of animal keratin-associated proteins, including KAP6.1/6.2/6.3 from humans. Hair keratin-associated proteins (KAP) are a major component of the hair fibre and play crucial roles in forming a strong hair shaft through a cross-linked network with keratin intermediate filaments (KIF) [
].
Plant AtJ6-like proteins are related to Escherichia coli DnaJ. Arabidopsis AtJ6 contains an N-terminal J-domain, but which lacks the G/F, and C-rich domains characteristic of DnaJ. Their function is not clear.
Insulinoma-associated protein 1 (INSM1) is a zinc-finger transcription factor exclusively expressed in the foetal pancreas and nervous system, and in tumours of neuroendocrine origin. It can recruits cyclin D1 and HDACs, which confer transcriptional repressor activity [
]. It is involved in endocrine and neuronal cell differentiation []. In pancreas, it is activated by the islet-specific endocrine factor neurogenin 3, and subsequently regulates downstream target genes NeuroD1 and insulin during beta-cell maturation [].Transcription factor egl-46 is the C. elegans orthologue from human INSM2, which is involved in neuron differentiation [
].
This entry includes a group of proteins from Dictyosteliales and Acytosteliales, including DDB_G0292248 from Dictyostelium discoideum. Their function is not clear.
This entry represents a group of plant proteins, including nodulin homeobox protein (NDX) from Arabidopsis. AtNDX associates with single-stranded DNA and inhibits COOLAIR transcription, which in turn modifies FLC (FLOWERING LOCUS C) expression [
].
The late 100kDa protein (also known as L4) inhibits host translation while promoting late viral translation by ribosome shunting [
]. It blocks host cap-dependent translation by binding to eIF4G, displacing MKNK1 from cap initiation complexes and preventing EIF4E phosphorylation [].
Circoviruses are small circular single stranded viruses. This family is the capsid protein from viruses such as Porcine circovirus [
] and Beak and feather disease virus .
Atg8-interacting proteins (ATI1 and ATI2) are unique to plants. Under conditions of carbon starvation, ATI1 and ATI2 become associated with spherical compartments that dynamically move along the ER network [
]. ATI1 is also located on bodies associating with plastids, and it seems to be involved in autophagic plastid-to-vacuole trafficking through its ability to interact with both plastid proteins and ATG8 [].
This entry represents a group of leucine zipper containing proteins from plants, including ZPR1-4 from Arabidopsis. ZPR3 is a competitive inhibitor of the HD-ZIP III transcription factors in shoot apical meristem development [
].
Protein O-mannose kinase (POMK;
) is a type II membrane protein with a large lumenal domain. It phosphorylates the 6-position of O-mannose using ATP, a crucial step in the biosynthetic pathway of O-mannose glycan [
]. Mutations in the POMK gene cause a severe congenital muscular dystrophy, Walker-Warburg syndrome [].
In bacterial chemotaxis, cellular movement is directed in response to chemical gradients. Transmembrane chemoreceptors that sense the stimuli are coupled via coupling protein CheW with a signal transduction histidine kinase (CheA) [
,
]. CheA phosphorylates response regulators CheB and CheY. The two cytoplasmic proteins, CheW and CheA, both contain homologous SH3-like domains that interact with transmembrane chemoreceptors, or methyl accepting chemotaxis proteins (MCPs). CheV is a third type of protein with a CheW-like domain.In Bacillus subtilis, CheW and CheV may be partially redundant in coupling the receptors to CheA; however, they are both necessary for efficient chemotaxis [
]. CheV is phosphorylated in vitro on a conserved aspartate as a result of phosphoryl group transfer from phosphorylated CheA (CheA-P). This reaction is slower compared with the phospho-transfer reaction between CheA-P and one other response regulator of the system, CheB. It is part of a signal transduction pathway to facilitate adaptation to attractants []. In Helicobacter pylori, CheV paralogues and CheW are not redundant and seem to have separate roles in chemotaxis []. CheV is a two-domain protein with an N-terminal CheW-like (SH3-like) domain and a C-terminal CheY-like receiver domain. It is often regarded as a version of CheW, where the CheW-like domain is fused to the receiver domain [].This group contains chemotaxis response regulator proteins CheW.
RELCH is a RAB11 effector protein that regulates intracellular cholesterol distribution from recycling endosomes to the trans-Golgi network through its interactions with RAB11 and OSBP [
].
HMBOX1 binds to 5'-TTAGGG-3' repeats in telomeric DNA and may play a role in recruitment of the telomerase complex to telomeres [
,
]. It also plays a role in the alternative lengthening of telomeres (ALT) pathway in telomerase-negative cells where it promotes formation and/or maintenance of ALT-associated promyelocytic leukemia bodies (APBs) [].
NodN (nodulation factor N) contains a single hot dog fold similar to those of the peroxisomal Hydratase-Dehydrogenase-Epimerase (HDE) protein, and the fatty acid synthase beta subunit [
]. Rhizobium and related species form nodules on the roots of their legume hosts, a symbiotic process that requires production of Nod factors, which are signal molecules involved in root hair deformation and meristematic cell division. The nodulation gene products, including NodN, are involved in producing the Nod factors, however the role played by NodN is unclear [,
,
,
].
The Arabidopsis genome contains seven GLUTAMINE DUPMER (GDU)-encoding genes. GDUs stimulate amino acid export by activating nonselective amino acid facilitators [
]. GDU1 has been shown to induce the secretion of glutamine from hydathodes and increased amino acid content in leaf apoplasm and xylem sap [].
Ras proteins are membrane-associated molecular switches that bind GTP and GDP
and slowly hydrolyze GTP to GDP []. This intrinsic GTPase activity of Ras is regulated by a family of proteins collectively known as 'GAP' or GTPase-activating proteins [,
]. RasGAP proteins are usually quite large (from 765 residues for sar1 to 3079residues for IRA2) but share only a limited (about 250 residues) region of
sequence similarity, referred to as the 'catalytic domain' or RasGAP domain.The most conserved region within this domain contains a 15 residue motif which
seems to be characteristic of this family of proteins []. Note: There are distinctly different GAPs for the Rap and Rho/Rac subfamilies of Ras-like proteins that do not share sequence similarity with Ras GAPs [
].
This entry represents YAP1-binding protein 1/2 (YBP1/2) from fungi. They are involved in cellular response to oxidative stress [
]. In Candida albicans, Ybp1 and Gpx3 mediate Cap1-dependent oxidative stress responses [].
The keratin-associated proteins (KAPs) are fundamental components of hair and wool fibres [
]. This entry represents KRTAP8-1, which is a high sulphur (HS) KAP [].
Poly(gamma-glutamic acid), or PGA, is an extracellular structural polymer found in Bacillus subtilis and a number of other species. PGA is sometimes capsule-forming, sometimes secretory, and may be produced by Gram-positive (single plasma membrane) and Gram-negative (inner and outer membranes) bacteria, so export and/or attachment machinery may differ from system to system. Members of this family occur in a subset of PGA operons, in lineages that include Francisella, Leptospira, Treponema, Thermotoga, Fusobacterium, and Clostridium, amongst others.
This three-domain protein is restricted to the spirochetes and widely distributed (excepting Borrelia). It has a conserved C-terminal SPASM domain, a 4Fe-4S binding domain shared by a number of peptide-modifying and heme-modifying radical SAM proteins. It has a central radical SAM domain, although half the members have lost the signature 4Fe-4S-binding Cys residues, fail to register with the radical SAM domain definition of model in entry
, and must be considered pseudo-SAM proteins. PSI-BLAST shows a relationship between the N-terminal domain and various predicted glycosyltransferases (e.g. Bacillus subtilis SpsF) and cytidyltransferases. In some Treponema species, this protein appears to split into two tandem genes.
Parathyroid hormone-related protein (PTH-rP) is structurally related to parathyroid hormone (PTH) [
] and seems to play a physiological role in lactation, possibly as a hormone for the mobilisation and/or transfer of calcium to the milk. It also regulates chondrocytic differentiation and bone formation [].This family also includes the zebrafish PTH family member Pth4, unique to noneutherian vertebrates, which is a regulator of bone mineral accrual acting through phosphate homeostasis []..
Human nucleolar protein 7 (NOL7) is a tumour suppressor that acts as a regulator of angiogenesis [
,
]. It has been shown to regulate thrombospondin-1 expression post-transcriptionally [
].
This entry includes CLAVATA3/ESR (CLE)-related proteins 5, 6, 7, 12, 13 and 53. CLE12 and CLE13 control the nodule numbers by interacting with the SUPER NUMERIC NODULES (SUNN)-dependent auto-regulation of nodulation [
,
].This entry also includes CLE-4A-1 and CLE-4A-3 from Globodera rostochiensis (Golden nematode worm). They mimics host plant CLE extracellular signal peptides that regulate cell fate [
].The CLE proteins share a C-terminal CLE domain with CLV3, a small secreted polypeptide that is active as a ligand and has a function in shoot apical meristem maintenance [
]. In general, the CLE-related proteins are C-terminally processed to generate an active CLE peptide []. These small secreted peptide hormones then function in a variety of developmental and physiological processes [,
]. CLV3 and other A-type CLE peptides are involved in the suppression of stem cell development in root and shoot development, in contrast to the B-type CLE peptides, CLE41 and CLE44, in the case of Arabidopsis, which are not [].
This entry represents the polymerase acidic (PA) protein from influenza virus. PA plays an essential role in viral RNA transcription and replication by forming the heterotrimeric polymerase complex together with PB1 and PB2 subunits [
,
].
L14 is an eukaryote-specific ribosomal protein from the 60S ribosomal subunit, which is conserved in some but not all archaea. In yeast, L14 assembles in the nucleolus at an early stage into pre-60S particles [
]. Auto-antibodies to RPL14 in humans have been associated with systemic lupus erythematosus [].
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 archaebacterial ribosomal protein L14e.
This entry represents a group of small, cysteine-rich plant proteins, also known as defensin-like proteins. They share sequence similarity to the PCP (pollen coat protein) family [
].
Pilin is a component of type IV pilus (T4P), a polar flexible filament, which consists of a single polypeptide chain arranged in a helical configuration of five subunits per turn, which is involved cell adhesion, microcolony formation, twitching motility and transformation [
,
]. Gram-negative bacteria produce pilin which is characterised by the presence of a very short leader peptide of 6 to 7 residues, followed by a methylated N-terminal phenylalanine residue and by a highly conserved sequence of about 24 hydrophobic residues, of the NMePhe type pilin [,
].
This entry includes SATB1/2 from animals. SATB1 is a global gene regulator that acts as a "docking site"for several chromatin remodeling enzymes and recruits corepressors (HDACs) or coactivators (HATs) directly to promoters [
]. SATB1 can bind DNA specifically to the consensus SATB1-binding sequence (CSBS) consisting of two 5'-TAATA-3' half-sites that are arranged as inverted repeats flanking a central cytosine or guanine. It can also bind DNA non-specifically []. SATB1 has been shown to bind to the nuclear matrix attachment regions (MARs) of the immunoglobulin heavy chain intronic enhancer [], while SATB2 has been shown to bind to the MARs of the endogenous immunoglobulin micro locus in pre-B cells and enhances gene expression [].SATB1 is an identified oncogene, its increased expression is associated with poor prognosis in many cancers []. Mutations in the SATB2 gene cause SATB2-associated syndrome (SAS), characterised by developmental delay/intellectual disability with absent or limited speech development, craniofacial abnormalities, behavioral problems, dysmorphic features, and palatal and dental abnormalities [,
].
CASP8-associated protein 2 (CASP8AP2), also known as FLASH, is involved in various cellular functions, such as cell cycle progression, transcriptional regulation, the regulation of apoptosis, and the regulation of histone gene expression [
]. It is an essential component of Cajal bodies and is involved in the apoptosis receptor signaling pathway [].FLASH contains the N terminus required for histone pre-mRNA processing, the C-terminal segment which forms a SANT/Myb-like domain, and a small central region which binds Ars2 essential for cell cycle progression [
]. Its N-terminal domain has been found to form a 2:1 heterotrimer with Lsm11 for histone pre-mRNA 3'-end processing [].
This entry includes beta-catenin-like protein 1 (CTNNBL1) and related proteins from animals, fungi and plants. Mammalian CTNNBL1is an AID (activation-induced cytidine deaminase)-interacting factor that is required for immunoglobulin class switch recombination [
].
This is a family of proteins from single-stranded DNA bacteriophages. Scaffold proteins B and D are required for procapsid formation. Sixty copies of the internal scaffold protein B are found in the procapsid [
].
This entry represents the Microviridae F protein family, including capsid protein F and capsid protein VP1. Capsid protein F is the major capsid component in single-stranded DNA bacteriophages. 60 copies of this protein are present in the virion [
].
Like MutT (
), MutX protein hydrolyses all canonical nucleoside
triphosphates at different rates, with a preference for dGTP, yielding nucleoside monophosphates and inorganic pyrophosphate [
]. Despite thesimilarity in enzymatic activity, the two proteins have distinct primary
and quaternary structures. Their sequences share only a small region of similarity (the MutT domain), and under the same conditions in which
MutT exists as a monomer in solution, MutX behaves as a trimer [].
This entry includes both frizzled proteins and secreted frizzled-related proteins (SFRP).Frizzleds are seven transmembrane-spanning proteins that constitute an unconventional class of G protein-coupled receptors [
]. They have important regulatory roles during embryonic development [,
].Frizzleds expose their large N terminus on the extracellular side. The N-terminal, extracellular cysteine-rich domain (CRD) has been implicated as the Wnt binding domain and its structure has been solved [
]. The cysteine-rich domain of Frizzled (Fz) is shared with other receptor tyrosine kinases that have roles in development including the muscle-specific receptor tyrosine kinase (MuSK), the neuronal specific kinase (NSK2), and ROR1 and ROR2. The cytoplasmic side of many Fz proteins has been shown to interact with the PDZ domains of PSD-95 family members and is thought to have a role in the assembly of signalling complexes. The conserved cytoplasmic motif of Fz, Lys-Thr-X-X-X-Trp, is required for activation of the beta-catenin pathway, and for membrane localisation and phosphorylation of Dsh.In Drosophila melanogaster, the frizzled locus is involved in planar cell polarity, which is the coordination of the cytoskeleton of epidermal cells to produce a parallel array of cuticular hairs and bristles [
,
]. In the wild-type wing, all hairs point towards the distal tip [], whereas in Fz mutants, the orientation of individual hairs with respect both to their neighbours and to the organism as a whole is altered. In the developing wing, Fz function is required for cells to respond to the extracellular polarity signal as well as the proximal-distal transmission of an intracellular polarity signal.In Caenorhabditis elegans, protein mom-5 is the equivalent of frizzled [
].Three main signalling pathways are activated by agonist-activated Frizzled proteins: the Fz/beta-catenin pathway, the Fz/Ca2+ pathway and the Fz/PCP (planar cell polarity) pathway [
]. The Wnt/beta-catenin pathway is the best studied signalling pathway involving Fz receptors. In the Wnt/beta-catenin pathway the first downstream cytoplasmic components activated by Fz signalling include Dishevelled (Dsh) and/or its regulatory kinases.There are secreted forms of Fz, known as soluble or secreted frizzled-related proteins (sFRPS), which function as modulators of Wnt signaling through direct interaction with Wnts [
]. They consist of only the amino-terminal cysteine rich domain (CRD), but no transmembrane segments. These secreted forms may bind to Wnt proteins in solution and thereby change the activity of Wnts. Such as FRP/FrzB, which consist of the CRD only and can act as secreted antagonists of Wnt signalling.
Members of this protein family are the pyridoxal phosphate-dependent enzyme EgtE, which catalyzes the final step in the biosynthesis of ergothioneine [
].
This entry includes poorly characterised, lipid-binding proteins containing an SCP2 sterol-binding domain. Non-specific lipid-transfer protein-like 1 (NSL-TP1 or nlt-1) from
Caenorhabditis elegansis found in the peroxisome. Protein UbiT (also known as YhbT) from
Escherichia coliis cytosolic. The oleate-induced peroxisomal protein POX18 from the yeast
Candida tropicalis, which is involved in beta-oxidation of long-chain fatty acids and nonspecific lipid-transfer activity, despite not having the catalytic cysteine conserved [
]. In vitro Arabidopsis thalianaSCP2 (AtSCP2) has been shown to enhance the transfer of lipids between membranes [
] and is localised in the peroxisome [].
Members of this protein family are restricted to the Pyrococcus and Thermococcus genera of the archaea. Member proteins have a C-terminal, Cys-containing predicted surface anchor domain, where the Cys may be the site of cleavage and lipid attachment (see domain
). Members also contain a region crowded with 10 invariant Cys in 60 residues (see domain
), possible ligands to some redox cofactor.
MIX forms an all α-helical fold comprising seven α-helices that fold into a single domain. The distribution of helices is similar to a number of scaffold proteins, namely HEAT repeats, 14-3-3, and tetratricopeptide repeat proteins, suggesting that MIX mediates protein-protein interactions [
].
Members of this protein family are restricted to members of the Actinobacteria (Mycobacterium smegmatis, Streptomyces hygroscopicus, Geodermatophilus obscurus, Pseudonocardia dioxanivorans, Saccharomonospora marina, etc) that synthesize PQQ. This small protein, 155 amino acids long on average, is found regularly next to a much larger protein, a PQQ-dependent oxidoreductase, and might be a companion subunit or an accessory protein such as chaperone involved in cofactor insertion.
Contact-dependent growth inhibition (CDI) is a widespread mechanism of bacterial competition. CDI+ bacteria deliver the toxic C-terminal region of contact-dependent inhibition A proteins (CdiA-CT) into neighbouring target bacteria and produce CDI immunity proteins (CdiI) which bind CdiA-CT domains and neutralize their toxic activity to protect against self-inhibition. CdiI immunity proteins are also variable and only neutralize their cognate CdiA-CT toxins. Structure analysis of CdiI from Escherichia coli 536 (EC536) shows that is composed of a single domain and that it blocks the interaction with substrate, strongly suggesting that the immunity protein occludes the nuclease active site [
].
CENP-P is a component of the CENPA-CAD (nucleosome distal) complex. The centromere, which is the basic element of chromosome inheritance, is epigenetically determined in mammals. CENP-A, the centromere-specific histone H3 variant, assembles an array of nucleosomes and it is this that seems to be the prime candidate for specifying centromere identity. CENP-A nucleosomes directly recruit a proximal CENP-A nucleosome associated complex (NAC) comprised of CENP-M, CENP-N and CENP-T, CENP-U(50), CENP-C and CENP-H. Assembly of the CENP-A NAC at centromeres is dependent on CENP-M, CENP-N and CENP-T. Additionally, there are seven other subunits which make up the CENP-A-nucleosome distal (CAD) centromere, CENP-K, CENP-L, CENP-O, CENP-P, CENP-Q, CENP-R and CENP-S, also assembling on the CENP-A NAC [
]. Fta7 is the equivalent component of the fission yeast Sim4 complex [].
This family of proteins is functionally uncharacterised. This family of proteins is found in chordates and includes the human integral membrane protein TMEM174 protein.
Myotubularin-related protein 14 (MTMR14, also known as Jumpy) belongs to the myotubularin family, whose members are dual-specificity phosphatases that act primarily to dephosphorylate phosphoinositides (PIs). They act specifically on PI3P and PI3,5P2, dephosphorylating them to form PIP and PI5P, respectively [
]. MTMR14 interacts with early autophagosomes and negatively regulates progression through the steps of autophagy []. It has been linked to the a congenital muscle disorder known as myopathy, centronuclear, 1 (CNM1) [].
Membrane-anchored junction protein (MAJIN) is a meiosis-specific telomere-associated protein involved in meiotic telomere attachment to the nucleus inner membrane, a crucial step for homologous pairing and synapsis. It is a component of the MAJIN-TERB1-TERB2 complex, which promotes telomere cap exchange by mediating attachment of telomeric DNA to the inner nuclear membrane and replacement of the protective cap of telomeric chromosomes: in early meiosis, the MAJIN-TERB1-TERB2 complex associates with telomeric DNA and the shelterin/telosome complex. During prophase, the complex matures and promotes release of the shelterin/telosome complex from telomeric DNA. In the complex, MAJIN acts as the anchoring subunit to the nucleus inner membrane. MAJIN shows DNA-binding activity, possibly for the stabilization of telomere attachment on the nucleus inner membrane [
].
This entry includes CENP-Q and Fta7 proteins. CENP-Q is one of the components that assembles onto the CENP-A-nucleosome distal (CAD) centromere. Fta7 is the equivalent component of the fission yeast Sim4 complex [
]. The centromere, which is the basic element of chromosome inheritance, is epigenetically determined in mammals. CENP-A, the centromere-specific histone H3 variant, assembles an array of nucleosomes and it is this that seems to be the prime candidate for specifying centromere identity. CENPA nucleosomes directly recruit a proximal CENPA-nucleosome-associated complex (NAC) comprised of CENP-M, CENP-N and CENP-T, CENP-U(50), CENP-C and CENP-H. Assembly of the CENPA NAC at centromeres is dependent on CENP-M, CENP-N and CENP-T. Additionally, there are seven other subunits which make up the CENPA-nucleosome distal (CAD) centromere, CENP-K, CENP-L, CENP-O, CENP-P, CENP-Q, CENP-R and CENP-S, also assembling on the CENP-A NAC [
]. Fta7 is the equivalent component of the fission yeast Sim4 complex [].
The centromere, which is the basic element of chromosome inheritance, is epigenetically determined in mammals. All active centromeres are characterised by the presence of long arrays of nucleosomes in which CENP-A replaces histone H3. CENP-A assembles an array of nucleosomes and it is this that seems to be the prime candidate for specifying centromere identity. CENP-A nucleosomes directly recruit a proximal CENP-A nucleosome associated complex (NAC) comprised of CENP-M, CENP-N and CENP-T, CENP-U(50), CENP-C and CENP-H. Assembly of the CENP-A NAC at centromeres is dependent on CENP-M, CENP-N and CENP-T. Additionally, there are seven other subunits which make up the CENP-A-nucleosome distal (CAD) centromere, CENP-K, CENP-L, CENP-O, CENP-P, CENP-Q, CENP-R and CENP-S, also assembling on the CENP-A NAC [
]. CENP-U is one of the components that assembles onto the CENP-A-nucleosome associated complex (NAC).
This entry represents the kinetochore-associated protein Dsn1/Mis13.In Saccharomyces cerevisiae, Dsn1 acts as essential component of the kinetochore MIND complex, which is required for the spindle checkpoint and kinetochore integrity. MIND plays a role in establishing a bipolar spindle-kinetochore interaction by joining kinetochore subunits contacting DNA to those contacting microtubules [
,
].In Schizosaccharomyces pombe, Mis13 acts as a component of the NMS (Ndc80-MIND-Spc7) super complex which has a role in kinetochore function during late meiotic prophase and throughout the mitotic cell cycle. It is required for correct segregation of chromosomes and for maintaining the inner centromere structure [
, ].
Spermatogenesis-associated protein 48 is also known as post-meiotic spermatogenesis protein 1 [
]. In humans, it is found in the chromosomal position, C7orf72.Lack of this protein leads to small testis and defective spermatogenesis in mice. SPATA48 has homologs in humans, mice, chimpanzees and macaques but these proteins have no conserved domains and their function is unclear [
].
This is a motif found only in Iroquois-class homeodomain proteins. It has unknown function. Examples include iroquois-class homeodomain protein IRX-4, and homeobox proteins caupolican and araucan, which control proneural and vein forming genesand are positive transcriptional controllers of achaete-scute. They may act as activators that interact with the transcriptional initiation complex assembled on the achaete and scute promoters.
The 43kDa postsynaptic protein is a peripheral membrane protein thought to be involved
in the anchoring or stabilisation of the nicotinic acetylcholine receptor at synaptic
sites []. It may link the receptor to the postsynaptic cytoskeleton through direct association with actin or spectrin. The 43kDa protein is
highly conserved across species. Two highly conserved regions, one encompassing the N terminus and the other near the C terminus, may be important for interaction of the
protein with other components of the postsynaptic membrane.
This entry represents the Protein SPO16 homologue (SPO16, also known as Synaptonemal complex reinforcing element SCRE), including the mammalian orthologue of budding yeast Spo16. It plays a key role in reinforcing the integrity of the central element of the synaptonemal complex (SC), resulting in the SC stabilization which ensures the progression of meiotic prophase I in male and female germ cells [
. It promotes homologous recombination and crossing-over in meiotic prophase I via its association with SHOC1 [
]. It is also required for the localization of TEX11 and MSH4 to recombination intermediates [].
RADX is an RPA-like, single-strand DNA binding proteinrecruited to replication forks to maintain genome stability [
]. It has been shown to modulate stalled fork protection by antagonizing RAD51 [].
A number of eukaryotic proteins that seem to be involved with sterol synthesis and/or its regulation have been found [
] to be evolutionary related. These include mammalian oxysterol-binding protein (OSBP), a protein of about 800 amino-acid residues that binds a variety of oxysterols (oxygenated derivatives of cholesterol) [,
]; yeast Osh1, a protein of 859 residues that also plays a role in ergosterol synthesis []; yeast proteins Hes1 and Kes1, highly related proteins of 434 residues that seem to play a role in ergosterol synthesis [,
]; Probable transporter efuK from the fungi Hormonema carpetanum, which is involved in the biosynthesis of enfumafungin []; and OSBP-related proteins (ORP) from plants such as Arabidopsis thaliana [].The core structure of OSBP has a large meander β-sheet of 12 strands wrapped around the N-terminal (distorted) alpha-hairpin. It shares some similarity with transmembrane β-barrel proteins.
This family is found in chordata. The deletion of Spata46 in mice resulted in subfertility with abnormal sperm head shape and a failure of sperm-egg fusion [
]. Spata46 has also been shown to localize to the nuclear membrane by a transmembrane region in the N-terminal.
This family includes the HopA1 effector protein from Pseudomonas syringae. Structurally this protein has an alpha + beta fold [
]. The effector protein HopA1 was shown to affect the EDS1 complex by binding EDS1 directly and activating the immune response signaling pathway.
