MAPK-interacting and spindle-stabilising protein (MISS) is rich in prolines and has four potential MAPK-phosphorylation sites, a MAPK-docking site, a PEST sequence (PEST motif) and a bipartite nuclear localisation signal. The endogenous protein accumulates during mouse meiotic maturation and is found as discrete dots on the MII (meiosis metaphase II) spindle. MISS is the first example of a physiological MAPK-substrate that is stabilised in MII that specifically regulates MII spindle integrity during the cytostatic factor (CSF) arrest [
].
This family of uncharacterised proteins shows a low level of similarity (possibly meaningful) to the predicted membrane protein YLR220W, which is involved in calcium homeostatis. It shows no similarity to any other characterised protein.
This family is represented in three of the first four completed archaeal genomes, with two members in Archaeoglobus fulgidus.
The function of ADP-ribosylation factor-like protein 10 (ARL10) is not clear. It belongs to the Arf family of small GTPases that contains a unique structural device, known as "interswitch toggle"[
].
This entry includes ADP-ribosylation factor-like protein 8A/8B (Arl8a/Arl8b) and related proteins. In animals, Arl8a and Arl8b are small GTPases that regulate axonal transport of synaptic vesicle proteins and lysosome motility [
,
]. Human Arl8a/Arl8b (also known as GIE2/GIE1) are required for chromosome segregation [].
This entry represents a group of Arf-like small GTP-binding proteins, including ARL2/3 from animals, Cin4 from budding yeasts, Alp41 from fission yeasts and ARL2 from Arabidopsis. They are involved in microtubule-dependent processes [
]. Despite the structural similarity of ARL2 and ARL3, they have different biochemical properties and biological functions []. ARL2 plays roles in both the regulation of tubulin folding and microtubule destruction. It is also essential to a number of mitochondrial functions, including mitochondrial morphology, motility, and maintenance of ATP levels []. ARL3 is required for normal cytokinesis and cilia signaling []. Alp41 is essential for the cofactor-dependent biogenesis of microtubules [].
The epithelial membrane proteins (EMP-1, -2 and -3), peripheral myelin protein 22 (PMP22), and lens fibre membrane intrinsic protein (LMIP) comprise a protein family on the basis of sequence and structural similarities [
]. Each family member is a small hydrophobic membrane glycoprotein, ~160-170 amino acids in length, and shares a common predicted transmembrane (TM) topology of 4 TM domains, with intracellular N- and C-termini [].A role for the EMP family members in the control of cell growth has been suggested [
]. EMP-1 is expressed at high levels in proliferating cells, and at reduced levels in cells undergoing growth arrest []. In contrast, PMP22, which is co-expressed with EMP-1 in a range of tissues, displays an inverse pattern of regulation, with high levels of expression in cultured cells undergoing growth arrest []. It has therefore been proposed that these proteins may have reciprocal functions in the control of cell quiescence and proliferation.EMP-2, previously termed XMP, was identified by expressed sequence tag (EST) database searching, pursuing sequences similar to EMP-1 [
]. Mus musculus (Mouse) and Homo sapiens (Human) isoforms have been cloned. EMP-2 is expressed in a range of tissues, including ovary, heart, lung and intestine. Although its function has not been elucidated, it has been postulated that EMP-2 may be involved in the regulation of cell proliferation on the basis of its sequence similarity to EMP-1 [].
The epithelial membrane proteins (EMP-1, -2 and -3), peripheral myelin protein 22 (PMP22), and lens fibre membrane intrinsic protein (LMIP) comprise a protein family on the basis of sequence and structural similarities [
]. Each family member is a small hydrophobic membrane glycoprotein, ~160-170 amino acids in length, and shares a common predicted transmembrane (TM) topology of 4 TM domains, with intracellular N- and C-termini [].A role for the EMP family members in the control of cell growth has been suggested [
]. EMP-1 is expressed at high levels in proliferating cells, and at reduced levels in cells undergoing growth arrest []. In contrast, PMP22, which is co-expressed with EMP-1 in a range of tissues, displays an inverse pattern of regulation, with high levels of expression in cultured cells undergoing growth arrest []. It has therefore been proposed that these proteins may have reciprocal functions in the control of cell quiescence and proliferation.EMP-3, previously termed YMP, was identified by expressed sequence tag (EST) database searching, pursuing sequences similar to EMP-1 [
]. Mouse, human and rat isoforms have been cloned. EMP-3 is expressed in a range of tissues, including peripheral blood leukocytes, ovary and intestine. Although its function has not been elucidated, it has been postulated that EMP-3 may be involved in the regulation of cell proliferation on the basis of its sequence similarity to EMP-1 [].
The epithelial membrane proteins (EMP-1, -2 and -3), peripheral myelin protein 22 (PMP22), and lens fibre membrane intrinsic protein (LMIP) comprise a protein family on the basis of sequence and structural similarities [
]. Each family member is a small hydrophobic membrane glycoprotein, ~160-170 amino acids in length, and shares a common predicted transmembrane (TM) topology of 4 TM domains, with intracellular N- and C-termini [].PMP22, also termed growth-arrest specific protein (GAS3), is a structural component of compact myelin in the peripheral nervous system. Aberrant expression of the PMP22 gene, and mutations in the protein, are associated with a variety of hereditary peripheral motor and sensory neuropathies [
]. An intra-chromosomal duplication containing the PMP22 gene is found in the majority of patients suffering from the autosomal dominant demyelinating neuropathy Charcot-Marie-Tooth disease 1A (CMT1A) []. In addition, rare point mutations in PMP22 have been found in non-duplication CMT1A patients and in the severe congenital peripheral neuropathy Dejerine-Sottas syndrome [].PMP22 is also implicated in the control of cell proliferation. Its expression levels are up-regulated in cells undergoing growth arrest [
], and it has been shown that modulating PMP22 levels in cultured Schwann cells exerts a profound effect on the length of the G1 phase of the cell cycle []. It has also been demonstrated that over-expression of PMP22 in NIH 3T3 fibroblast cells induces apoptosis [].
The epithelial membrane proteins (EMP-1, -2 and -3), peripheral myelin protein 22 (PMP22), and lens fibre membrane intrinsic protein (LMIP) comprise a protein family on the basis of sequence and structural similarities [
]. Each family member is a small hydrophobic membrane glycoprotein, ~160-170 amino acids in length, and shares a common predicted transmembrane (TM) topology of 4 TM domains, with intracellular N- and C-termini [].EMP-1, previously termed tumour-associated membrane protein (TMP), was originally isolated from a mouse brain tumour [
]. Human, rat and rabbit isoforms have also been identified. EMP-1 is expressed in a wide range of tissues, including heart, placenta, lung, skeletal muscle, kidney and small intestine []. A role for the protein in the control of cell growth has been suggested []. EMP-1 is expressed at high levels in proliferating cells, and at reduced levels in cells undergoing growth arrest []. In contrast, PMP22, which is co-expressed with EMP-1 in a range of tissues, displays an inverse pattern of regulation, with high levels of expression in cultured cells undergoing growth arrest []. It has therefore been proposed that these proteins may have reciprocal functions in the control of cell quiescence and proliferation.
This entry represents the Non-structural Protein 6 (NSP6) found in coronaviruses. Coronaviruses encode large replicase polyproteins which are proteolytically processed by viral proteases to generate mature Nonstructural Proteins (NSPs) [
]. NSP6 is a membrane protein containing 6 transmembrane domains with a large C-terminal tail []. NSP6 from the avian coronavirus, infectious bronchitis virus (IBV) and the mouse hepatitis virus (MHV) have been shown to localise to the ER and to generate autophagosomes []. Coronavirus NSP6 proteins have also been shown to limit autophagosome expansion. This may favour coronavirus infection by reducing the ability of autophagosomes to deliver viral components to lysosomes for degradation []. NSP6 from IBV, MHV and severe acute respiratory syndrome coronavirus (SARS-CoV) have also been found to activate autophagy [,
].
Coronaviruses encode large replicase polyproteins which are proteolytically processed by viral proteases to generate mature Nonstructural Proteins (NSPs) [
]. NSP6 is a membrane protein containing 6 transmembrane domains with a large C-terminal tail []. NSP6 from the avian coronavirus, infectious bronchitis virus (IBV) and the mouse hepatitis virus (MHV) have been shown to localise to the ER and to generate autophagosomes []. Coronavirus NSP6 proteins have also been shown to limit autophagosome expansion. This may favour coronavirus infection by reducing the ability of autophagosomes to deliver viral components to lysosomes for degradation []. NSP6 from IBV, MHV and severe acute respiratory syndrome coronavirus (SARS-CoV) have also been found to activate autophagy [,
].This entry represents Non-structural protein 6 (NSP6) from deltacoronavirus.
This entry represents the non-structural protein 6 (NSP6) from betacoronavirus. Recently, it was reported that SARS-CoV-2 NSP6 binds TANK binding kinase 1 (TBK1) to suppress interferon regulatory factor 3 (IRF3) phosphorylation which suppresses IFN-I signalling and production more efficiently than SARS-CoV and MERS-CoV [
].Coronaviruses (CoV) redirect and rearrange host cell membranes as part of the viral genome replication and transcription machinery; they induce the formation of double-membrane vesicles in infected cells. CoV non-structural protein 6 (NSP6), a transmembrane-containing protein, together with NSP3 and NSP4, have the ability to induce double-membrane vesicles that are similar to those observed in severe acute respiratory syndrome (SARS) coronavirus-infected cells []. By itself, NSP6 can generate autophagosomes from the endoplasmic reticulum. Autophagosomes are normally generated as a cellular response to starvation to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy may provide an innate defense against virus infection, or conversely, autophagosomes can promote infection by facilitating the assembly of replicase proteins []. In addition to initiating autophagosome formation, NSP6 also limits autophagosome expansion regardless of how they were induced, i.e. whether they were induced directly by NSP6, or indirectly by starvation or chemical inhibition of MTOR signalling. This may favour coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation [].
This entry represents the non-structural protein 6 (NSP6) from gammacoronavirus.Coronaviruses (CoV) redirect and rearrange host cell membranes as part of the viral genome replication and transcription machinery; they induce the formation of double-membrane vesicles in infected cells. CoV non-structural protein 6 (NSP6), a transmembrane-containing protein, together with NSP3 and NSP4, have the ability to induce double-membrane vesicles that are similar to those observed in severe acute respiratory syndrome (SARS) coronavirus-infected cells [
]. By itself, NSP6 can generate autophagosomes from the endoplasmic reticulum. Autophagosomes are normally generated as a cellular response to starvation to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy may provide an innate defense against virus infection, or conversely, autophagosomes can promote infection by facilitating the assembly of replicase proteins []. In addition to initiating autophagosome formation, NSP6 also limits autophagosome expansion regardless of how they were induced, i.e. whether they were induced directly by NSP6, or indirectly by starvation or chemical inhibition of MTOR signalling. This may favour coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation [].
This entry represents the non-structural protein 6 (NSP6) from alphacoronavirus.Coronaviruses (CoV) redirect and rearrange host cell membranes as part of the viral genome replication and transcription machinery; they induce the formation of double-membrane vesicles in infected cells. CoV non-structural protein 6 (NSP6), a transmembrane-containing protein, together with NSP3 and NSP4, have the ability to induce double-membrane vesicles that are similar to those observed in severe acute respiratory syndrome (SARS) coronavirus-infected cells [
]. By itself, NSP6 can generate autophagosomes from the endoplasmic reticulum. Autophagosomes are normally generated as a cellular response to starvation to carry cellular organelles and long-lived proteins to lysosomes for degradation. Degradation through autophagy may provide an innate defense against virus infection, or conversely, autophagosomes can promote infection by facilitating the assembly of replicase proteins []. In addition to initiating autophagosome formation, NSP6 also limits autophagosome expansion regardless of how they were induced, i.e. whether they were induced directly by NSP6, or indirectly by starvation or chemical inhibition of MTOR signalling. This may favour coronavirus infection by compromising the ability of autophagosomes to deliver viral components to lysosomes for degradation [].
CCDC117 is a family of coiled-coil proteins found in eukaryotes. Proteins in this family are typically between 203 and 279 amino acids in length. There is a conserved MELV sequence motif. The function is not known.
RAD52 motif-containing protein 1 (RDM1) is involved in DNA damage repair pathway and the cell response to the anti-cancer drug cisplatin [
,
]. RDM1 contains a small RD motif that is shared with the recombination and repair protein RAD52, and an RNA recognition motif (RRM). The RD motif is responsible for the acidic pH-dependent DNA-binding properties of RDM1. It interacts with ss- and dsDNA, and may act as a DNA-damage recognition factor by recognizing the distortions of the double helix caused by cisplatin-DNA adducts in vitro. In addition, due to the presence of RRM, RDM1 can bind to RNA as well as DNA [].
The DNA single-strand annealing proteins (SSAPs), such as RecT, Red-beta, ERF and Rad52, function in RecA-dependent and RecA-independent DNA recombination pathways. This family includes proteins related to Rad52. These proteins contain two helix-hairpin-helix motifs [
].
This is a family of herpesvirus UL49 tegument proteins. It was shown that interactions between herpesvirus envelope and tegument proteins may play a role in secondary envelopment during herpesvirus virion maturation.
This family of proteins plays a role in the moulting cycle of nematodes, which involves the synthesis of a new collagen-rich cuticle underneath the existing cuticle and the subsequent removal of the old cuticle [
].
This family comprises the 11kDa non-structural proteins found in segment S11 of the Rotavirus genome. They may form part of a complex that is involved in the replication of the genome.
CotE is a morphogenic protein that is required for the assembly of the outer coat of the endospore [
] and spore resistance to lysozyme []. CotE also regulates the expression of cotA, cotB, cotC and other genes encoding spore outer coat proteins []. The timing of cotE expression has been shown in Bacillus subtilis to affect spore coat morphology but not lysozyme resistance [].
Curli are a class highly aggregated surface fibres that are part of a complex extracellular matrix. They promote biofilm formation in addition to other activities. CsgE is a non-structural protein involved in curli biogenesis [
]. CsgE forms an outer membrane complex with the curli assembly proteins CsgG and CsgF [].
The calcitonin-receptor-like receptor can function as either a calcitonin-gene-related peptide or an adrenomedullin receptor. The receptors function is modified by receptor activity modifying protein (RAMP). RAMPs are single-transmembrane-domain proteins [
].
This family of proteins, which contains SH3BGRL3, is functionally uncharacterised. SH3BGRL3 is a highly conserved small protein, which is widely expressed and shows a significant similarity to glutaredoxin 1 (GRX1) of Escherichia coli which is predicted to belong to the thioredoxin
superfamily. However, SH3BGRL3 lacks both conserved cysteine residues, which characterisethe enzymatic active site of GRX. This structural feature raises the possibility that SH3BGRL3 and its homologues could function as
endogenous modulators of GRX activity []. Adapter SH3BGRL from mammals is also included in this entry. This protein may function as a ubiquitin ligase-substrate adapter that bridges proteins together or proteins with mRNAs [
,
].
This entry represents the surface-adhesin protein E from Pasteurellaceae. Adhesin E plays a role in pathogenesis [
]. It binds to host proteins including plasminogen, vitronectin and laminin [].
The rat seminal vesicle contains six major androgen-dependent secretory proteins referred to as SVS I-VI. The SVS I-III proteins appear to be components of the rat copulatory plug, with the SVS II protein being the major component [
].This entry represents a repeat that is found in seminal vesical proteins.
The ribosomal proteins catalyse ribosome assembly and stabilise the rRNA, tuning the structure of the ribosome for optimal function. Evidence suggests that, in prokaryotes, the peptidyl transferase reaction is performed by the large subunit 23S rRNA, whereas proteins probably have a greater role in eukaryotic ribosomes. Most of the proteins lie close to, or on the surface of, the 30S subunit, arranged peripherally around the rRNA [
]. The small subunit ribosomal proteins can be categorised as primary binding proteins, which bind directly and independently to 16S rRNA; secondary binding proteins, which display no specific affinity for 16S rRNA, but its assembly is contingent upon the presence of one or more primary binding proteins; and tertiary binding proteins, which require the presence of one or more secondary binding proteins and sometimes other tertiary binding proteins.The small ribosomal subunit protein S17 is known to bind specifically to the 5' end of 16S ribosomal RNA in Escherichia coli (primary rRNA binding protein), and is thought to be involved in the recognition of termination codons. Experimental evidence [
] has revealed that S17 has virtually no groups exposed on the ribosomal surface.This entry represents archaeal ribosomal S17 proteins.
ACBD5 is an acyl-CoA binding protein which acts as the peroxisome receptor for pexophagy but is dispensable for aggrephagy and nonselective autophagy. It binds medium- and long-chain acyl-CoA esters [
].
GARP, or glutamic acid/alanine-rich protein, is one of a subset of major surface molecules on Trypanosoma species. They are all surface-orientated, immunodominant, and highly charged. GARP is interesting as its expression coincides with the loss and gain of variant surface glycoprotein (VSG) molecules in the tsetse vector. It has an extended helical bundle structure that is homologous to the core surface structure of VSG, suggesting that it might replace the bloodstream VSG as the trypanosomes differentiate inside the tsetse vector after a blood-meal [
].
This is a family of phage tail tube proteins including protein XkdM from phage-like element PBSX protein (
) whose structure adopts a beta barrel flanked with alpha helical regions [
].
This entry represents the transcription activators mating-type alpha1, such as HMLalpha1 and MATalpha1. Initiation of meiosis in Saccharomyces cerevisiae (Baker's yeast) is regulated by mating type and nutritional conditions that restrict meiosis to diploid cells grown under starvation conditions [
]. Saccharomyces mating-type (MAT) switching occurs by gene conversion using one of two donors, HMLalpha and HMRa [].
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. Members of this entry are mainly found in proteobacteria.
Proteins in this family include PapB, DaaA, FanA, FanB and AfaA.P pili, or fimbriae, are ~68A in diameter and 1 micron in length, the
bulk of which is a fibre composed of the main structural protein PapA [].At its tip, the pilus is terminated by a fibrillum consisting of repeating
units of the PapE protein. This, in turn, is topped by the adhesins, PapFand PapG, both of which are needed for receptor binding. The tip fibrillum
is anchored to the main PapA fibre by the PapK pilus-adaptor protein. PapH,an outer membrane protein, then anchors the entire rod in the bacterial
envelope []. A cytoplasmic chaperone (PapD) assists in assembling the monomers of the macromolecule in the membrane.
All of the functional pap genes are arranged in a cluster (operon) on the
Escherichia coli genome. It is believed that selective pressure exerted by the host's urinal and intestinal tract isoreceptors forced the spread of this
operon to other strains via lateral transfer []. PapB, encoded within the cluster, acts as a transcriptional regulator of the functional pap genes
and is located in the bacterial cytoplasm []. Its mechanism involvesdifferential binding to separate sites in the cluster, suggesting that
this protein is both an activator and repressor of pilus-adhesion transcription. The protein shares similarity with other E. coli fimbrial-
adhesion transcription regulators, such as AfaA, DaaA and FanB.
This entry includes budding yeast Rec114 protein and its homologue, Rec7, from S. pombe. They are required for meiotic intragenic recombination but not for mitotic recombination [
,
]. REC114 is one of 10 genes required for initiation of meiotic recombination in Saccharomyces cerevisiae [
]. Located on chromosome XIII, it is transcribed only in meiosis and has no detectable function in mitosis []. REC114 has been shown to possess an intron and is one of only three genes in yeast with 3' introns []. The 3' splice site utilised in REC114 is a very rare AAG sequence - only three other genes in yeast use this non-consensus sequence []. It appears that the intron is not essential for expression of REC114 and is not absolutely required for meiotic function. Nevertheless, it is conserved in evolution - two other species of yeast contain an intron at the same location in their REC114 genes [].
The UL11 gene product (also known as cytoplasmic envelopment protein 3) of herpes simplex virus is a membrane-associated tegument protein that is incorporated into the HSV virion and functions in viral envelopment [
]. UL11 is acylated, which is crucial for lipid raft association [].
CyaE belongs to the outer membrane factor (OMF) family, which forms complexes with the cytoplasmic membrane transporters that transport (export) of various solutes (heavy metal cations; drugs, oligosaccharides, proteins, etc.) across the two envelopes of the Gram-negative bacterial cell envelope in a single energy-coupled step [
]. CyaE, together with CyaB and CyaD, is necessary for transport of calmodulin-sensitive adenylate cyclase-hemolysin (cyclolysin) [].
Intraflagellar transport (IFT) particle, which consists of complex A and B, is involved in assembling and maintaining eukaryotic cilia and flagella. Intraflagellar transport protein 20 (IFT20) is a subunit of the intraflagellar transport complex B (consists of IFT172, 88, 81, 80, 74/72, 57/55, 52, 46, 27, 20) [
,
]. IFT20 is associated with the Golgi complex and may play a role in the trafficking of ciliary membrane proteins from the Golgi complex to the cilium [,
]. Besides its function in cilia, IFT20 also regulates immune synapse assembly in T cells []. In an yeast two hybrid experiment, IFT20 exhibited a strong interaction with IFT57/Hippi and the kinesin II subunit, KIF3B [].
Slx9 is required for pre-rRNA processing. In Saccharomyces cerevisiae, Slx9 is associated with the 90S pre-ribosome and 43S small ribosomal subunit precursor [
]. The early stages of ribosomes biogenesis includes processing of the 35S pre-ribosomal RNA transcript into the mature 18S, 5.8S, and 25S rRNA molecules. The 35S precursor contains external transcribed spacer elements (5' and 3'-ETS) at either end as well as internal transcribed spacers (ITS1 and ITS2) that separate the mature sequences [
]. Slx9 is implicated in the processing events that remove the ITS1 spacer sequences [].
In Saccharomyces cerevisiae, Met8 is a bifunctional dehydrogenase (
) and ferrochelatase (
) [
]. It catalyses the final two steps in the biosynthesis of sirohaem, involving a NAD(+)-dependent dehydrogenation of precorrin-2 to generate sirohydrochlorin followed by ferrochelation to yield sirohaem []. Siroheme is a heme-like prosthetic group used by sulfite and nitrite reductases []. The structure of Met8 has been resolved. A single active site, Asp141, has been shown to play an essential role in both dehydrogenase and chelatase processes []. This entry also includes precorrin-2 dehydrogenase (also known as siroheme synthase) from bacteria which catalyzes the dehydrogenation of precorrin-2 to form sirohydrochlorin, a precursor in siroheme biosynthesis and in anaerobic adenosylcobalamin biosynthesis [
].
This entry represents a domain found in actinobacterial proteins, including EspA and EspE from Mycobacteria.The ESX-1 operon is present in a number of Mycobacteria strains [
]. In Mycobacterium tuberculosis (Mtb) the type VII ESX-1 secretion apparatus is used to translocate the key virulence factors EsxA (ESAT-6) and EsxB (CFP-10). In Mtb, the EspA protein is encoded by the unlinked espACD operon [
]. The EspA protein of Mycobacterium tuberculosis is essential for the type VII ESX-1 protein secretion apparatus []. EspA, ESAT-6, and CFP-10 are each critical for virulence of pathogenic mycobacteria and secretion of these three proteins, is mutually dependent [,
]. EspA undergoes Cys138-mediated homodimerization, although the process is not required for EspA or ESAT-6 secretion []. EspE is encoded by the ESX-1 operon [
]. In M. smegmatis it has been shown to colocalise with SaeC at, or near, the cell pole []. In M. smegmatis secretion of the heterodimer of EsxAB (ESAT-6/CFP-10) is dependent on the co-secretion of proteins encoded from both esx1 (eg., EspE) and non-esx1 genes (eg., EspA) [].
Proteins in this family are multi-pass membrane proteins from eukaryotes.
Proteins in this family are typically between 94 and 119 amino acids in length.
This domain can be found in CENP-B homologue protein 1/2 (CBHP-1/2)and ARS-binding protein 1 (Abp1) from Shizosaccharomyces pombe. The domain, referred to as domain 1, is DNA-binding and makes up half of the N-terminal region [].
This is the N-terminal region found on proteins encoded by C10orf90, also known as FATS. Most of the family members carry ALMS motif on their C-terminal (
). SiRNA mediated functional analysis suggest that the C10orf90 encoded proteins have a role in centrosomal functions [
].
Spermatid-specific manchette-related protein 1 (SMRP1) interacts with alpha-tubulin and may be involved in differentiation or function of ciliated cells [
]. SMRP1 may play a role in spermatogenesis [].
This domain is found at the C terminus of BMP-2-inducible protein kinase (BMP2K) and related proteins. BMP2K may be involved in osteoblast differentiation [
,
].
This entry represents a family of proteins conserved in fungi whose function is unknown. It includes Cu(2+) suppressing and bleomycin sensitive protein 1 thought to be involved in bleomycin tolerance with links to DNA repair and/or proteasome function.
A specific region of the Influenza B virus NS1 protein, which includes part of its effector domain, blocks the covalent linkage of mouse ISG15 to its target proteins both
in vitroand in infected cells. Of the several hundred proteins induced by interferon (IFN) alpha/beta, the ubiquitin-like ISG15 protein is one of the most predominant. Influenza A virus employs a different strategy: its NS1 protein does not bind the ISG15 protein, but little or no ISG15 protein is produced during infection [
].
RXLR proteins constitute a family of phytopathogen avirulence or effector proteins. They are defined by a secretion signal peptide followed by a conserved N-terminal domain with the sequence motif RXLR (Arg-Xaa-Leu-Arg) consensus sequence. The RXLR part is required for translocation inside plant cells, although it appears to be dispensable for the biochemical activity of the effectors when expressed directly inside host cells. The effector activity resides in the C-terminal part of the family, which activate effector-triggered immunity in plants that carry a corresponding resistance (R) protein. The C-terminal region exhibits a fold appears to be able to evolve to outwit the host as the latter tries to acquire new immunity [
].
Cytokinesis in yeasts involves a family of proteins whose essential function is to bind Cdc14-family phosphatase and prevent this from being sequestered and inhibited in the nucleolus. This is the highly conserved N terminus of a family of proteins which act as cytokinesis checkpoint controls by allowing cells to cope with cytokinesis defects. These proteins are required for rDNA silencing and mini-chromosome maintenance [
].
This entry represents a C-terminal part of the head domain of the dsDNA viruses, no RNA stage, Adenovirus. This is a globular head domain with an anti-parallel β-sandwich fold formed by two four-stranded β-sheets with the same overall topology as human adenovirus fibre heads. This C-terminal domain is the receptor-binding domain of the avian adenovirus long fibre [
].
Matrix (M) protein is an important structural component of rhabdovirus virions, and also plays a number of roles during the replication cycle of the virus [
]. It is involved in condensing and targeting the ribonucleoprotein (RNP) coil to the plasma membrane. M interacts specifically with the transmembrane spike protein (G) and it is important for the incorporation of G protein into budding virions [].
The dystrophin glycoprotein complex (DGC) is a membrane-spanning complex that links the interior cytoskeleton to the extracellular matrix in muscle. The sarcoglycan complex is a subcomplex within the DGC and is composed of several muscle-specific, transmembrane proteins (alpha-, beta-, gamma-, delta- and zeta-sarcoglycan). The sarcoglycans are asparagine-linked glycosylated proteins with single transmembrane domains. This family contains beta, gamma, delta and zeta members [
,
].
This is a family of Coronavirus nonstructural protein NS2. Phosphoamino acid analysis confirmed the phosphorylated nature of NS2 and identified serine and threonine as its phosphorylated amino acid residues [
]. It was also demonstrated that the ns2 gene product is not essential for Murine hepatitis virus replication in transformed murine cells [].
This entry contains proteins of no known function. They are found predominantly in Vibrio and cyanobacterial species and are characterised by having a NKWYS sequence motif.
Protein VI is a structural protein of the adenoviral capsid. It shuttles between the nucleus and the cytoplasm and links hexon to the nuclear import machinery via an importin alpha/beta-dependent mechanism [
]. It also mediates adenovirus endosome penetration during cell entry [,
].
This entry is represented by Bacteriophage P4, Ash protein [
]. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.
This is a family of late cornified envelope proteins that are expressed in skin [
]. They are precursors of the cornified envelope of the stratum corneum, the outermost layer of the epidermis.
This entry represents ribosomal protein S6 kinase (or p70S6K). S6 kinase is a serine/threonine kinase (STK) that catalyses the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. It contains only one catalytic kinase domain, unlike p90 ribosomal S6 kinases (RSKs). S6 kinase is part of the mammalian target of rapamycin (mTOR) pathway, which is a key regulator of cell growth via the regulation of protein synthesis. Both S6 kinase and eukaryotic initiation factor 4E-binding protein 1 (4EBP-1) are key mTOR effectors of cell growth [
,
,
,
]. S6 kinase specifically phosphorylates ribosomal protein S6 in response to insulin or several classes of mitogens. S6 kinase is activated by serine/threonine phosphorylation and protein kinase C, and is inactivated by type 2A phosphatase []. S6 kinase interacts with PPP1R9A/neurabin-1 []. S6 kinase also plays a pivotal role glucose homeostasis. Its targets include the insulin receptor substrate IRS-1, among others. Mammals contain two isoforms of S6 kinase, named S6K1 and S6K2 (or S6K-beta). S6 kinase is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.
This is a family of plasmid encoded proteins involved in plasmid replication. The role of RepA in the replication process is not clearly understood [
].
TMEM201, also known as SAMP1, is a RanGTP binding transmembrane protein found in the inner nuclear membrane [
]. It is functionally associated with the LINC complex protein Sun1 and proteins of the A-type lamina network [
].This entry represents the C-terminal domain of TMEM201.
The chromosomal passenger complex of Aurora B kinase, INCENP, and Survivin has essential regulatory roles at centromeres and the central spindle in mitosis. Cell division cycle-associated protein 8, also known as Borealin, is also a member of the complex. Approximately half of Aurora B in mitotic cells is complexed with INCENP, Borealin, and Survivin [
]. Depletion of Borealin by RNA interference delays mitotic progression and results in kinetochore-spindle mis-attachments and an increase in bipolar spindles associated with ectopic asters [].
The Antirepressor protein ant from Salmonella phage P22 prevents the prophage p22 c2 repressor protein from binding to its operators. It also inhibits the action of other prophage repressor proteins, including those of phages lambda and 434. The synthesis of antirepressor is negatively regulated by the protein products of the two other immi genes, mnt and arc [
,
,
]. This entry represents the N-terminal domain of this protein and similar proteins from tailed bacteriophages (Caudovirales) and bacterial prophages mostly found in Proteobacteria.
Centrosomal protein of ~126kDa (CEP126), previously known as KIAA1377 [
], localises to the centrosome, pericentriolar satellites and the base of the primary cilium. It is an important regulator of centrosomal function. Cep126 is necessary for microtubule (MT) organisation, association of the MT array with the centrosome, and is also required for the formation of the primary cilium [].
This entry includes F-box only protein 30 (Fbxo30) [
] and F-box only protein 40 (Fbxo40) []. Fbxo30 is a ubiquitin ligase required for muscle loss, hence it is also known as muscle ubiquitin ligase of the SCF complex in atrophy-1 (MUSA1) []. Fbxo40 id an E3 ubiquitin ligase that induces IRS1 ubiquitination and breakdown specifically in skeletal muscle cells and only upon IGF1 (insulin-like growth factor 1) stimulation [].
This entry includes packaging protein 3 (also known as L1) I-leader protein from adenovirus. L1 is involved in viral genome packaging through its interaction with packaging protein 1 and 2 [
,
]. The function of I-leader protein is not clear [].
Members of this family are found in a small number of taxonomically well-separated species, yet are strongly conserved, suggesting lateral gene transfer. Members are found in Treponema denticola, Clostridium acetobutylicum, and several of the firmicutes. The function of this protein is unknown.
Peptidoglycan synthesis (PG) biosynthesis involves the formation of peptidoglycan precursor lipid II (undecaprenyl-pyrophosphate-linked N-acetyl glucosamine-N-acetyl muramic acid-pentapeptide) on the cytosolic face of the cell membrane. Lipid II is then translocated across the membrane and its glycopeptide moiety becomes incorporated into the growing cell wall mesh.MviN, renamed as MurJ, is a lipid II flippase essential for cell wall peptidoglycan synthesis [
,
]. Unlike most MviN proteins, the mycobacterial MviN orthologue possess an extended C-terminal region that contains an intracellular pseudo-kinase domain and an extracellular domain resembling carbohydrate-binding proteins [].
Junctional cadherin 5-associated protein (JCAD) is a component of VE-cadherin-based cell-cell junctions in endothelial cells [
]. The cell-cell or adherens junction is an adhesion complex that plays a crucial role in the organisation and function of epithelial and endothelial cellular sheets. These junctions join the actin cytoskeleton to the plasma membrane to form adhesive contacts between cells or between cells and extracellular matrix. The junctions also mediate both cell adhesion and cell-signalling. JCAD localises close to the apical membrane in epithelial cells.
This group represents multiphosphoryl transfer protein fruB. It is part of the phosphoenolpyruvate-dependent sugar phosphotransferase system (sugar PTS), a major carbohydrate active -transport system, catalyses the phosphorylation of incoming sugar substrates concomitantly with their translocation across the cell membrane.
Fig1 is a integral membrane protein that facilitates Ca2+ influx and cell fusion during mating of Saccharomyces cerevisiae [
]. It is required for yeast mating differentiation [].
This entry includes cell fusion protein Dni1 from fission yeasts and Fig1 from budding yeasts. Dni1 is a cell membrane protein which plays a relevant role in coordinating membrane organization and cell wall remodeling during mating [
]. Fig1 is a integral membrane protein that facilitates Ca2+ influx and cell fusion during mating of Saccharomyces cerevisiae [].
Competence is the ability of a cell to take up exogenous DNA from its environment, resulting in transformation. It is widespread among bacteria and is probably an important mechanism for the horizontal transfer of genes. DNA usually becomes available by the death and lysis of other cells. Competent bacteria use components of extracellular filaments called type 4 pili to create pores in their membranes and pull DNA through the pores into the cytoplasm. This process, including the development of competence and the expression of the uptake machinery, is regulated in response to cell-cell signalling and/or nutritional conditions [
].This group represents a competence protein D (also known as DNA transformation protein ComD) from Pasteurellaceae.
There is currently no experimental data for members of this group or their homologues, nor do they exhibit features indicative of any function. However, they possess a predicted signal peptide.
