Nonstructural protein 15, middle domain, alpha/betacoronavirus
Type:
Domain
Description:
The unique coronavirus transcription/replication machinery comprised of multiple virus-encoded non structural proteins (NSP) plays a vital role during initial and intermediate phases of the viral life cycle. NSP15 forms a hexamer made of dimers of trimers which is suggested to be a functional unit, responsible for the endoribonuclease activity. The NSP15 monomer consists of three domains: N-terminal, middle and C-terminal [
,
]. The catalytic function of NSP15 resides in the C-terminal NendoU domain. The active site carries six key residues conserved among SARS-CoV-2, SARS-CoV and MERS-CoV, suggesting that its activity is important for sustained replication in the host [,
].This entry represents the non-catalytic middle domain of NSP15 from alpha and beta coronaviruses. This domain is formed by ten β-strands organised into three β-hairpins. It creates concave surfaces that may serve as interaction hubs with other proteins and RNA [
,
]. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. This middle domain harbours residues involved in hexamer formation and in trimer stability [,
]. Oligomerization of Porcine DeltaCoronavirus (PDCoV) Nsp15 differs from that of the other coronaviruses; it has been shown to exist as a dimer and a monomer in solution [].
Nonstructural protein 15, middle domain, deltacoronavirus
Type:
Domain
Description:
The unique coronavirus transcription/replication machinery comprised of multiple virus-encoded non structural proteins (NSP) plays a vital role during initial and intermediate phases of the viral life cycle. NSP15 forms a hexamer made of dimers of trimers which is suggested to be a functional unit, responsible for the endoribonuclease activity. The NSP15 monomer consists of three domains: N-terminal, middle and C-terminal [
,
]. The catalytic function of NSP15 resides in the C-terminal NendoU domain. The active site carries six key residues conserved among SARS-CoV-2, SARS-CoV and MERS-CoV, suggesting that its activity is important for sustained replication in the host [,
].This entry represents the middle domain of NSP15 from deltacoronaviruses. This domain is formed by ten beta strands organised into three beta hairpins. It creates concave surfaces that may serve as interaction hubs with other proteins and RNA [
,
]. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. This middle domain harbours residues involved in hexamer formation and in trimer stability [
,
]. Oligomerization of Porcine DeltaCoronavirus (PDCoV) Nsp15 differs from that of the other coronaviruses; it has been shown to exist as a dimer and a monomer in solution and that it inhibits type I interferon production independently of its endoribonuclease activity [,
].
Nonstructural protein 15, middle domain, gammacoronavirus
Type:
Domain
Description:
The unique coronavirus transcription/replication machinery comprised of multiple virus-encoded non structural proteins (NSP) plays a vital role during initial and intermediate phases of the viral life cycle. NSP15 forms a hexamer made of dimers of trimers which is suggested to be a functional unit, responsible for the endoribonuclease activity. The NSP15 monomer consists of three domains: N-terminal, middle and C-terminal [
,
]. The catalytic function of NSP15 resides in the C-terminal NendoU domain. The active site carries six key residues conserved among SARS-CoV-2, SARS-CoV and MERS-CoV, suggesting that its activity is important for sustained replication in the host [,
].This entry represents the non-catalytic middle domain of NSP15 from gammacoronaviruses. This domain is formed by ten beta strands organised into three beta hairpins. It creates concave surfaces that may serve as interaction hubs with other proteins and RNA [,
]. Coronavirus Nsp15 from Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV), human Coronavirus 229E (HCoV229E), and Murine Hepatitis Virus (MHV) form a functional hexamer. This middle domain harbours residues involved in hexamer formation and in trimer stability [,
]. Oligomerization of Porcine DeltaCoronavirus (PDCoV) Nsp15 differs from that of the other coronaviruses; it has been shown to exist as a dimer and a monomer in solution and that it inhibits type I interferon production independently of its endoribonuclease activity [,
].
Nonstructural protein 15, N-terminal domain, alpha/beta-coronavirus
Type:
Domain
Description:
The unique coronavirus transcription/replication machinery comprised of multiple virus-encoded non structural proteins (NSP) plays a vital role during initial and intermediate phases of the viral life cycle. NSP15 forms a hexamer made of dimers of trimers which is suggested to be a functional unit, responsible for the endoribonuclease activity. The NSP15 monomer consists of three domains: N-terminal, middle and C-terminal [
,
]. The catalytic function of NSP15 resides in the C-terminal NendoU domain. The active site carries six key residues conserved among SARS-CoV-2, SARS-CoV and MERS-CoV, suggesting that its activity is important for sustained replication in the host [,
].This entry represents the N-terminal oligomerization domain of the NSP15, which stabilises the hexamer and is critical for its formation [
]. This domain is composed of three-stranded antiparallel β-sheet and two α-helices [,
,
,
].This entry represents the N-terminal oligomerisation domain of the NSP15 from alpha and beta coronaviruses.
TRAPPC14 (also known as MAP11) is a microtubule associated protein that regulates preciliary trafficking of Rabin8 (a guanine nucleotide exchange factor for Rab8) and ciliogenesis [
]. It is a specific subunit of the TRAPP (transport protein particle) II complex, a highly conserved vesicle tethering complex that functions in late Golgi trafficking as a membrane tether [,
,
]. TRAPPC14 is dispensable for TRAPPII complex integrity but mediates Rabin8 association with the TRAPPII complex []. It also modulates YAP1 activity as transcriptional regulator []. Mutations in the MAP11 gene cause microcephaly in humans and zebrafish [].
This is a family of putative Gram-negative, largely proteobacterial, type IV (conjugal DNA-protein transfer or VirB) secretory pathway (IVSP) proteins.
This entry represents a presumed C-terminal domain of ubiquitin 3 binding proteins (But2). But2 is conserved in yeasts. It binds to Uba3 and is involved in the NEDD8 signalling pathway [
].
This entry represents the inner layer core protein VP3 from various Reoviruses, including Orbiviruses and Phytoreviruses, Reoviruses have dsRNA genomes of 10-12 linear segments [
]. VP3 proteins and their homologues are found in the Orbiviruses Epizootic hemorrhagic disease virus and Bluetongue virus (BTV) [], while the homologous VP2 protein is found in Broadhaven virus (BRD). VP3 proteins are also found in Phytoreviruses such as Rice dwarf virus (RDV).The inner layer protein VP3 is part of the virus core and makes a 'subcore' shell made up of 120 copies of the 100K protein. VP3 particles can also bind RNA and are fundamental in the early stages of viral core formation. VP3 is a large protein without apparent domain divisions, but has a number of all-alpha regions and one all-beta region near the C-terminal [
].
This family of proteins is found in eukaryotes and includes Required for drug-induced death protein 1 (RDD1) which regulates drug efflux through modulation of ABCB1 localization and activity [
,
].
Nonstructural protein 2, N-terminal domain, coronavirus
Type:
Domain
Description:
Coronavirus non-structural protein 2 (NSP2) is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. Viral-host protein interaction studies in SARS-CoV and SARS-CoV-2 found that this protein could interact with several host proteins, including prohibitin 1 (PHB1) and PHB2, which are implicated in a number of cellular functions, including cellular migration, differentiation and apoptosis [
,
]. NSP2 structure from SARS-CoV-2 has been recently solved and revealed that it has three zinc fingers, which may be involved in binding nucleic acids and regulating intracellular signalling pathways []. NSP2 has been pointed as an interesting target to develop anti-SARS-COV-2 therapies as it may play important roles during viral infection.This entry represents the N-terminal of NSP2 which covers the zinc fingers [
].
Non-structural protein 2, C-terminal domain, coronavirus
Type:
Domain
Description:
Coronavirus non-structural protein 2 (NSP2) is encoded by ORF1a/1ab and proteolytically released from the pp1a/1ab polyprotein. Viral-host protein interaction studies in SARS-CoV and SARS-CoV-2 found that this protein could interact with several host proteins, including prohibitin 1 (PHB1) and PHB2, which are implicated in a number of cellular functions, including cellular migration, differentiation and apoptosis [
,
]. NSP2 structure from SARS-CoV-2 has been recently solved and revealed that it has three zinc fingers, which may be involved in binding nucleic acids and regulating intracellular signalling pathways []. NSP2 has been pointed as an interesting target to develop anti-SARS-COV-2 therapies as it may play important roles during viral infection.This domain is found at the C-terminal of NSP2 in alpha and betacoronaviruses. It is found in two copies in some viral NSP2 proteins.
Protein of unknown function DUF2160, transmembrane
Type:
Family
Description:
The members of this family of hypothetical prokaryotic proteins have no known function. It is thought that they are transmembrane proteins, but their function has not been inferred yet.
This is the tudor domain found in DNA repair protein Crb2. Structural and functional studies of Crb2 and its mammalian homologue 53BP1 indicate that the conserved tandem-Tudor domain of 53BP1 and Crb2 preferentially interacts with H4K20me2, though it also binds to H4K20me1 [
]. Furthermore, despite low amino acid sequence similarity, Crb2 is structurally related to 53BP1 in having two tudor domains and a conserved dimethyllysine-binding pocket, and that, like 53BP1, it directly binds H4-K20me2 [].
Synaptotagmin-like protein 4 , FYVE-related domain
Type:
Domain
Description:
Synaptotagmin-like protein 4 (SYTL4, Slp4), also known as granuphilin or exophilin-2, belongs to the synaptotagmin-like protein family (Slp), which is a group of putative membrane trafficking proteins [
]. The characteristic feature of the Slp family is the N-terminal Slp homology domain (SHD), which functions as a Rab27-binding domain and C-terminal tandem C2 domains (known as the C2A domain and C2B domain), putative Ca2+-binding motifs [,
]. SHD consists of two conserved regions, designated SHD1 and SHD2, which may function as protein interaction sites. The SHD1 and SHD2 of Slp4 are separated by a putative FYVE zinc finger, which resembles a FYVE-related domain that is structurally similar to the canonical FYVE domains but lacks the three signature sequences: an N-terminal WxxD motif (x for any residue), the central basic R(R/K)HHCRxCG patch, and a C-terminal RVC motif.There are several alternatively spliced isoform of Slp4. Slp4-a (granuphilin-a) has two C2 domains, whereas Slp4-b (granuphilin-b) contains only the first C2 domain. Expression of Slp4-a inhibits regulated secretion in endocrine cells. Slp4-a binds to both the GTP- and GDP-bound forms of Rab27A and inhibits a specific GTP/GDP exchange cycle required for dense-core vesicle exocytosis [
]. Slp4 has been detected in the pancreatic islet, in particular in insulin-positive beta cells, and in pituitary []. This entry represents the FYVE-related domain of synaptotagmin-like protein 4.
ESX-1 secretion-associated protein EspB, PE domain
Type:
Domain
Description:
The ESX-1 secretion system is an important virulence determinant in Mycobacterium tuberculosis. ESX-1 secreted protein B (EspB) contains putative PE (Pro-Glu) and PPE (Pro-Pro-Glu) domains, and a C-terminal domain, which is processed by MycP1 protease during secretion. This domain represents the PE domain located at the N-terminal region of EspB which carries the conserved YxxxD/E secretion motif [
].
This phage protein family is expressed from within a cluster of tail- and base plate-producing genes [
]. It is a family of tail assembly chaperone proteins [].
Lactococcus phage single-stranded DNA binding protein
Type:
Family
Description:
This single-stranded DNA binding protein (SSB) is found in Lactococcus phage. It can stimulate RecA-mediated homologous recombination. Its structure is a variation of the typical oligonucleotide/oligosaccharide binding-fold of single-stranded DNA binding proteins [
].
Secreted frizzled-related proteins (Sfrps) are soluble proteins containing an Netrin (NTR) domain C-terminal to a cysteine-rich Frizzled domain [
]. They show diverse functions and are thought to work in Wnt signaling indirectly, as modulators or antagonists by binding Wnt ligands, and directly, via the Wnt receptor, Frizzled [].SFRP3 (also known as FRZB) regulates chondrocyte maturation and long bone development [
]. It is an antagonist of Wnt8 signalling [].
Divalent cation tolerance protein CutA, Enterobacteria
Type:
Family
Description:
This entry represents CutA, which is involved in resistance toward heavy metals [
]. It binds 1 copper ion per subunit. Similar sequences to CutA are found in several genomes. The metal binding sites are not conserved in many of the family members and their is currently unknown.
Respiratory synctial virus non-structural protein NS2
Type:
Family
Description:
The molecular structure and function of the NS2 protein is not known. However, mutants lacking the NS2 grow at
slower rates when compared to the wild-type yet NS2 is not essential for viral replication [].
The accessory gland of male insects is a genital tissue that secretes many components of the ejaculatory fluid, some of
which affect the female's receptivity to courtship and her rate of oviposition. The protein is expressed exclusively in themale accessory glands of adult Drosophila melanogaster. During copulation it is transferred to the female genital tract where it is rapidly altered [
].
Alginate O-acetyltransferase AlgI/D-alanyl transfer protein DltB
Type:
Family
Description:
The biochemically characterised members of this group are enzymes that transfer organic acids, typically fatty acids, onto hydroxyl groups of membrane-embedded targets. They contain a characteristic domain for O-acyl transferases, , in which a conserved histidine has been suggested to be the active site residue [
]. These enzymes are multispan membrane proteins involved in the modification of bacterial surface and extracellular polyliposaccharides that play a variety of roles in bacterial survival. Based on sequence similarity this family has been classified into two subgroups:1. DltB (
): DltB orthologues are present in Gram-positive bacteria. The dlt operon is responsible for D-alanine esterification of both lipoteichoic acid and wall teichoic acid. The dlt operon contains five genes, dltA-dltE; dltB codes for the enzyme that transfers D-alanine to the wall lipotechtoic acids [
].2. AlgI (
): AlgI homologues are present mainly in Gram-negative bacteria, though there are a few members from Gram-positive bacteria. The
algIgene is often linked to genes for type II membrane proteins that have the conserved amino acid motifs: P[x]K and RTD[x]HW. In Gram-negative bacteria, AlgI is involved in the synthesis of alginate (linear polymer of alpha L-gulunorate and beta-D-mannuronate linked by beta1-4 glycosidic bonds) [
]. AlgI paralogues in Pseudomonas syringae and Pseudomonas fluorescens are involved in the O-acetylation of cellulose [,
]. In the Gram-positive strain Clostridium acetobutylicum, an algIhomologue is also adjacent to the cellulose biosynthetic genes.
Synaptonemal complex protein 2, armadillo-repeat-like domain
Type:
Domain
Description:
Synaptonemal complex protein 2 (SYCP2) N-terminal region contains two separate subdomains an ARLD (armadillo-repeat-like domain) and an SLD (Spt16M-like domain). The ARLD domain belongs to the armadillo-repeat protein family. Armadillo-repeat units often form a superhelix, which typically provides a platform for many protein partners that transduce Wnt signaling, such as beta-catenin. The ARLD of mouse SYCP2 was found to associate with different protein partners, including CENP J and CENP F. ARLD structure is highly similar to that of the 'required for cell differentiation (RCD-1)' protein [
].
SLP adapter and CSK-interacting membrane protein (SCIMP) is a lipid tetraspanin-associated transmembrane adapter/mediator involved in major histocompatibility complex class II (MHC-II) signaling transduction [
]. SCIMP is expressed in B cells and other professional antigen-presenting cells (APCs) and is localised in the immunological synapse. Upon MHC-II stimulation, phosphorylated SCIMP binds to the SLP65 and to the inhibitory kinase Csk. SLP65 binding initiates the downstream signaling cascades, while Csk binding functions as a negative regulatory loop [].
This domain is found in the major vault protein.The major vault protein is the major polypeptide component of a large cellular ribonuclear protein complex found in the cytoplasm of eukaryotic cells (known as vaults). Several roles for vaults have been proposed. Vault proteins have been associated with development of multi-drug resistance [
]. They have also being implicated in the regulation of several cellular processes including transport mechanisms, signal transmission and immune responses [,
].
The Golgi to ER traffic (GET) complex is composed of Get1, Get2 and Get3. The complex is involved in the post-translational delivery of tail-anchored (TA) proteins to the endoplasmic reticulum [
]. Get1 and Get2 form a transmembrane complex and interact with Get3, an ATPase which recognises and selectively binds the transmembrane domain of TA proteins in the cytosol [,
].
Synaptonemal complex central element protein 3 (SYCE3), also known as testis-specific expressed gene 2, is a major component of the transverse central element (CE) of meiosis-specific synaptonemal complexes. SYCE3 enables chromosome loading of the other CE-specific proteins, which in turn promotes synapsis between homologous chromosomes [
]. SYCE3 may participate in the apoptosis of spermatogenic cells and the pathogenesis of cryptorchidism [].
Archaeal glycosylation protein B, peripheral domain
Type:
Domain
Description:
This domain is found in Archaeal Glycosylation B protein (AglB-Long) in A. fulgidus. When the domain, known as peripheral l (Pl), is combined with the central core (CC) and insertion (IS) sub-units, they form the C-terminal domain. It is thought that the C-terminal domain may contribute toward the increased thermal stability of the AglB proteins in the hyper-thermophilic [
].
Replication initiator protein A, C-terminal domain
Type:
Domain
Description:
This is the C-terminal domain (CTD) that can be found in the conserved replication initiator, RepA, essential for staphylococcal propagation. RepA CTD shared the strongest structural homology to the Enterococcus faecalis DnaD CTD, yet perform distinct functions. RepA CTD shows strong sequence homology between RepA_N plasmids in genus-specific clusters, suggesting that it may perform host-specific functions necessary for replication. The RepA CTD interacts with the host DnaG primase, which binds the replicative helicase. Structural data indicate that the RepA CTD exists as a monomeric entity, flexibly tethered to the DNA-bound NTD [
].
Utp8 is an essential component of the nuclear tRNA export machinery in Saccharomyces cerevisiae. It is a tRNA binding protein that acts at a step between tRNA maturation/aminoacylation, and translocation of the tRNA across the nuclear pore complex [
]. It is also co-purified with the U3 snoRNA containing complex, the small subunit (SSU) processome, which is required for the biogenesis of the 18S rRNA []. This entry also include the C1565.05 protein from Schizosaccharomyces pombe. Its function is not clear.
Torque teno virus, isolated initially from a Japanese patient with hepatitis of unknown aetiology, has since been found to infect both healthy and diseased individuals and numerous prevalence studies have raised questions about its role in unexplained hepatitis. ORF1 is a large 750 residue protein.
This entry represents the MAT Alpha1 domain, which is diverged from the MATA HMG-box domain [
]. All ascomycete MAT idiomorphs encode proteins with confirmed or putative DNA-binding motifs [,
]. The HMG-box domain can be found in a wide variety of DNA-binding proteins. In S. cerevisiae, there are two copies of Alpha1: one copy is localised at the MAT locus, the other is localised at the HML locus (MAT alpha 1). The HML locus (HML alpha 1) copy is usually silenced by the Sir2 histone deacetylase. MAT alpha 1 is a transcriptional coactivator involved in the regulation of mating-type alpha-specific gene expression. It activates mating-type alpha-specific genes with the help of the MADS-box containing Mcm1 transcription factor, which together bind cooperatively to PQ elements upstream of alpha-specific genes. The MCM1-MATalpha1 complex is required for the proper DNA-bending that is needed for transcriptional activation [
]. Alpha 1 interacts in vivo with Ste12, linking expression of alpha-specific genes to the alpha-pheromone () response pathway [
].
Microtubule-associated protein 1A/1B light chain 3C
Type:
Family
Description:
Autophagy-related protein LC3C (also known as microtubule-associated proteins 1A/1B light chain 3C) is a member of the ATG8 family, LC3 subfamily [
]. It is an ubiquitin-like modifier that plays a crucial role in antibacterial autophagy (xenophagy) through the selective binding of CALCOCO2 []. LC3C recruites all ATG8 family members to infecting bacteria such as Salmonella typhimurium [].
This entry represents the C-terminal domain of connexin 40 (Cx40). It interacts with the C-terminal and cytoplasmic loop domains of connexin 43 and with the cytoplasmic loop of another connexin 40 [
].Connexin 40 is a gap junction protein that has been linked to lone atrial fibrillation [
]. Gap junctions is composed of two hemichannels, each constituted by the oligomerisation of six connexins (Cx). This junction allows direct exchange of ions and small molecules between apposing cells [].
This is a family of ORF16 (or gp16) tail-phage P2-like proteins that forms part of the base-plate at the tip of the phage tail. The whole base-plate complex is involved in host recognition and attachment, and consists of several proteins derived from consecutive open-reading-frames. This central domain is expressed from ORF16 in the lactococcal P2-phage and forms a trimer [
].
This is the N-terminal domain of the fungal Fe-S cluster assembly protein Dre2. Yeast Dre2 has been implicated in cytosolic Fe-S protein biogenesis and in cell death regulation in response to oxidative stress [
].
This domain represents the N-terminal DNA-binding domain found in the PriA protein. This domain has been shown to bind the 3' end of the leading-strand arm of replication fork structures [
,
].Primosomal protein N', also known as ATP-dependent helicase PriA, is a component of the primosome, which is involved in replication, repair, and recombination. PriA serves as a sensor/stabiliser for an arrested replication fork and eventually promotes restart of DNA replication through assembly of a primosome. It also serves as a checkpoint protein that prevents the replicase from advancing in a strand displacement reaction on forks that do not contain a functional replicative helicase [
,
].
Paramyxovirus structural protein P/V, N-terminal domain
Type:
Domain
Description:
The replicative complex of Paramyxoviridae consists of proteins N, P and L. Transcription and replication are carried out on the N/RNA template by a RNA-dependent RNA polymerase complex, made of the phosphoprotein (P) and the large protein (L). P is organised into two moieties that are functionally and structurally distinct: a C-terminal moiety (PCT) and an N-terminal moiety (PNT). PCT is the most conserved in sequence and contains all regions required for virus transcription, whereas PNT, which is poorly conserved, provides several additional functions required for replication [
]. P protein plays a crucial role in the enzyme by positioning L onto the N/RNA template through an interaction with the C-terminal domain of N. Without P, L is not functional. The N-terminal part of P (PNT) is a chaperone for N and prevents it from binding to non-viral RNA in the infected cell [].This entry represents the PNT domain, found in several Paramyxoviridae (mainly Morbillivirus) structural protein P and V sequences [
]. V is a non-structural protein translated from an edited mRNA that contains an extra G residue.
The Hepatitis E virus (HEV) structural protein 2 (also known as ORF2) is a major viral capsid protein that encapsidates the viral genome. It has been shown to bind to the 5' end of the genomic RNA [
].Interestingly, ORF2 has an secreted isoform that inhibits antibody-mediated neutralization from the host [
].
Outer membrane lipoprotein carrier protein LolA-like
Type:
Family
Description:
In Escherichia coli, lipoproteins are anchored to the
periplasmic side of either the inner or outer membrane through N-terminal lipids, depending on the lipoprotein-sorting signal present atposition 2 [
]. Five Lol proteins are involved in the sorting and outer membrane localization of lipoproteins. LolCDE, an ATPbinding cassette (ABC) transporter, in the inner membrane releases outer membrane-directed lipoproteins from the inner membrane in an ATP-dependent manner, leading to the formation of a water-soluble complex between the lipoprotein and the molecular chaperone, LolA. The LolA-lipoprotein complex crosses the periplasm and then
interacts with outer membrane receptor LolB, which is essential for the anchoring of lipoproteins to the outer membrane [,
].E. coli lipoproteins are anchored to the inner or outer membrane depending on the residue at position 2. Aspartate at this
position makes lipoproteins specific to the inner membrane, whereas other residues cause the release of lipoproteins from the innermembrane [
].
The AML1 (also known as RUNX1) gene is rearranged by the t(8;21) translocation in acute myeloid
leukemia []. The gene is highly similar to the Drosophila melanogaster segmentation gene runt and to the mouse transcription factor PEBP2 alpha subunit gene [
].The region of shared similarity, known as the Runt domain, is responsible
for DNA-binding and protein-protein interaction. In addition to the highly-conserved Runt domain, the AML-1 gene product
carries a putative ATP-binding site (GRSGRGKS), and has a C-terminal regionrich in proline and serine residues. The protein (known as acute myeloid
leukemia 1 protein, oncogene AML-1, core-binding factor (CBF), alpha-B subunit, etc.) binds to the core site, 5'-pygpyggt-3', of a number of
enhancers and promoters. The protein is a heterodimer of alpha- and beta-subunits. The alpha-subunit
binds DNA as a monomer, and appears to have a role in the development ofnormal hematopoiesis. CBF is a nuclear protein expressed in numerous tissue
types, except brain and heart; highest levels have been found to occur in thymus, bone marrow and peripheral blood.
Conserved hypothetical protein CHP03704, protein-(glutamine-N5) methyltransferase
Type:
Family
Description:
This protein family is closely related to two different families of protein-(glutamine-N5) methyltransferase. The first is PrmB, which modifies ribosomal protein L3 in some bacteria. The second is PrmC (HemK), which modifies peptide chain release factors 1 and 2 in most bacteria and also in eukaryotes. The glutamine side chain-binding motif NPPY shared by PrmB and PrmC is N[VAT]PY in this family. The protein substrate is unknown.
CRISPR-associated protein Cas7, subtype I-B/Tneap, bacterial
Type:
Family
Description:
CRISPR (clustered regularly interspaced short palindromic repeat) is an adaptive immune system that provides protection against mobile genetic elements (viruses, transposable elements and conjugative plasmids). CRISPR clusters contain spacers, sequences complementary to antecedent mobile elements, and target invading nucleic acids. CRISPR clusters are transcribed and processed into CRISPR RNA (crRNA). This entry represents the Cas7 (DevR) protein which has a role in fruiting body development, sporulation and aggregation. Expression begins by 6 hours after starvation has initiated development and is under strong negative autoregulation [
,
].
This entry represents Rfa3 from budding yeasts. Rfa3 is a component of the replication protein A (RPA) complex, which binds to and removes secondary structure from ssDNA. The RPA complex is involved in DNA replication, repair, and recombination [
].
This entry represents Rad17 from budding yeast (the homologue of human and S. pombe Rad1). Rad17 is a component of the checkpoint clamp complex (Ddc1/Mec3/Rad17) involved in the surveillance mechanism that allows the DNA repair pathways to act to restore the integrity of the DNA prior to DNA synthesis or separation of the replicated chromosomes [
,
,
]. In S. cerevisiae, the Ddc1-Mec3-Rad17 complex associates with sites of DNA damage and modulates the Mec1 signaling pathway and the activation of Rad53 in response to DNA damage at phase G1 [
]. The complex also physically regulates DNA polymerase zeta-dependent mutagenesis by controlling the access of polymerase zeta to damaged DNA []. Contrary to its human counterpart, the 9-1-1 complex, the checkpoint clamp complex shows no detectable exonuclease activity []. It's worth noting that the name, Rad17, has been used for a different protein in human and S. pombe. The homologue of the human and S. pombe Rad17 in budding yeast is Rad24.
This entry represents a group of heavy metal-associated plant proteins, including Protein SODIUM POTASSIUM ROOT DEFECTIVE 1/2/3 (NAKR1/2/3) from Arabidopsis. NAKR1, also known as NPCC6, is necessary for phloem function and root meristem maintenance [
]. It also promotes flowering through mediating FT (FLOWERING LOCUS T) translocation from leaves to shoot apices []. It also plays an important role in the regulation of FT expression under long-day conditions []. NaKR3 is involved in the salt stress response [
].This family also includes ATX1 (also known as copper chaperone CCH) from Arabidopsis, which shows low sequence similarities with NAKR3 [
]. It plays an important role in copper homeostasis by conferring tolerance to excess of copper and subclinical copper deficiency during vegetative stage [].
This entry represents a domain is found in the protoxin portion of insecticidal proteins (parasporins, or Cry proteins) such as Cry1Ac from Bacillus thuringiensis (Bt). These proteins contain a proteolytically labile protoxin segment (in the C-terminal region) and a three-domain toxic core at the N terminus (domains I-III). This entry describes domain V, one of the four protoxin domains (domains IV-VII). Domains V and VII are β-rolls (similar to domain II or III) that closely resemble carbohydrate-binding modules found in sugar hydrolases. However, it is unclear which particular carbohydrates (if any) may serve as their ligands because residues on the putative sugar-binding interfaces are conserved neither in sequence nor in local structure. Structural analysis of Bt Cry1Ac indicates that there are putative disulfide crosslinks at the dimer interface mediated by cysteines within region 783-823 of this domain. Together with other cysteines, these create a three-dimensional network of cross-links across the crystal which may play a role in stabilizing mature Bt Cry1Ac [
].
ZCCHC4 is an rRNA N6-methyltransferase that specifically methylates the adenine in position 4220 of 28S rRNA [
]. N6-methylation of adenine(4220) in 28S rRNA is required for translation [].
This group represents cytadherence high molecular weight protein 2. It is a component of the cytoskeleton-like structure which stabilises the shape of the wall-less Mycoplasma [
,
]. This cytoskeleton-like network of accessory proteins containing HMW proteins 1 to 5 allows the proper anchoring of cytadhesin proteins in the mycoplasmal membrane at the attachment organelle [].
Ribonuclease P (Rnp) is a ubiquitous ribozyme that catalyzes a Mg2 -dependent hydrolysis to remove the 5'-leader sequence of precursor tRNA (pre-tRNA) in all three domains of life [
]. In bacteria, the catalytic RNA (typically ~120kDa) is aided by a small protein cofactor (~14kDa) []. Archaeal and eukaryote RNase P consist of a single RNA and archaeal RNase P has four or five proteins, while eukaryotic RNase P consists of 9 or 10 proteins. Eukaryotic and archaeal RNase P RNAs cooperatively function with protein subunits in catalysis [].In the hyperthermophilic archaeon Pyrococcus horikoshii OT3, RNase P is composed of the RNase P RNA (pRNA) and five proteins (PhoPop5, PhoRpp38, PhoRpp21, PhoRpp29, and PhoRpp30) [
,
]. This entry represents protein component 2 (Rnp2, also known as Pop5) of ribonuclease (RNase) P ().
Small GTPase superfamily, Uncharacterized protein MJ1339
Type:
Family
Description:
Small GTPases form an independent superfamily within the larger class of regulatory GTP hydrolases. This superfamily contains proteins that control a vast number of important processes and possess a common, structurally preserved GTP-binding domain [
,
]. Sequence comparisons of small G proteins from various species have revealed that they are conserved in primary structures at the level of 30-55% similarity [].Crystallographic analysis of various small G proteins revealed the presence of a 20kDa catalytic domain that is unique for the whole superfamily [
,
]. The domain is built of five alpha helices (A1-A5), six β-strands (B1-B6) and five polypeptide loops (G1-G5). A structural comparison of the GTP- and GDP-bound form, allows one to distinguish two functional loop regions: switch I and switch II that surround the gamma-phosphate group of the nucleotide. The G1 loop (also called the P-loop) that connects the B1 strand and the A1 helix is responsible for the binding of the phosphate groups. The G3 loop provides residues for Mg2 and phosphate binding and is located at the N terminus of the A2 helix. The G1 and G3 loops are sequentially similar to Walker A and Walker B boxes that are found in other nucleotide binding motifs. The G2 loop connects the A1 helix and the B2 strand and contains a conserved Thr residue responsible for Mg2 binding. The guanine base is recognised by the G4 and G5 loops. The consensus sequence NKXD of the G4 loop contains Lys and Asp residues directly interacting with the nucleotide. Part of the G5 loop located between B6 and A5 acts as a recognition site for the guanine base [].The small GTPase superfamily can be divided into at least 8 different families, including:Arf small GTPases. GTP-binding proteins involved in protein trafficking by modulating vesicle budding and uncoating within the Golgi apparatus.Ran small GTPases. GTP-binding proteins involved in nucleocytoplasmic transport. Required for the import of proteins into the nucleus and also for RNA export.Rab small GTPases. GTP-binding proteins involved in vesicular traffic.Rho small GTPases. GTP-binding proteins that control cytoskeleton reorganisation.Ras small GTPases. GTP-binding proteins involved in signalling pathways.Sar1 small GTPases. Small GTPase component of the coat protein complex II (COPII) which promotes the formation of transport vesicles from the endoplasmic reticulum (ER).Mitochondrial Rho (Miro). Small GTPase domain found in mitochondrial proteins involved in mitochondrial trafficking.Roc small GTPases domain. Small GTPase domain always found associated with the COR domain.This entry represents the Uncharacterized protein MJ1339 from Methanocaldococcus jannaschii, thought to be part of the wider small GTPase superfamily.
This entry represents Prohead assembly protein gp68 from Enterobacteria phage T4 (Bacteriophage T4) and similar proteins found in the viral family Myoviridae. Gp68 plays a role in the phage head size determination. About ten copies of this protein are found in the mature phage head [
]. It is predicted to have a secondary structure that consists of α-helical hairpins similar to supersecondary-structure-forming domains such as tetratricopeptide and HEAT repeats [].
DNA repair protein RAD51 homologue 2 (also known as RAD51B) is a Rad51 paralogue. The Rad51 paralogues are required for homologous recombination (HR) and the maintenance of genomic stability. RAD51B is involved in the repair of double-strand DNA breaks (DSBs) via HR [
]. It is part of the Rad51B-Rad51C-Rad51D-XRCC2 (BCDX2) complex, which acts in the BRCA1-BRCA2-dependent HR pathway [,
]. It has DNA-dependent ATPase activity and can bind single-stranded and double-stranded DNA []. Rad51B may have a specific function in Holliday junction processing in the HR pathway [].
This domain is found in proteins annotated as TonB dependent receptors, but it is also likely to be found in other membrane beta barrel proteins with other functions. It is part of a Pfam clan that includes other outer membrane protein β-barrel domains.
Zinc finger FYVE domain-containing protein 26 (ZFYVE26, also known as SPG15) is a phosphatidylinositol 3-phosphate-binding protein recruited to the midbody during cytokinesis and required for the abcission step in cytokinesis (cleaving of the midbody in two) [
]. It may also be required for efficient homologous recombination DNA double-strand break repair [].Mutations in ZFYVE26 cause spastic paraplegia 15, autosomal recessive (SPG15), which is a form of spastic paraplegia, a neurodegenerative disorder characterised by a slow, gradual, progressive weakness and spasticity of the lower limbs [
,
].
Chromodomain-helicase-DNA-binding protein 5, DEAH-box helicase domain
Type:
Domain
Description:
There are nine members of the Chromodomain, Helicase, DNA-binding (CHD) family. They are characterised by two chromodomains arranged in tandem, N-terminal to the ATPase/helicase domain. Chromodomains are comprised of a β-sheet folded against an α-helix that collectively mediates binding to methyl-lysine residues [
]. Chromodomain-helicase-DNA-binding protein 5 (CHD5) is a chromatin-remodeling protein that binds DNA through histones and regulates gene transcription. It is thought to specifically recognize and bind trimethylated 'Lys-27' (H3K27me3) and non-methylated 'Lys-4' of histone H3 and plays a role in the development of the nervous system by activating the expression of genes promoting neuron terminal differentiation [
]. In parallel, it may also positively regulate the trimethylation of histone H3 at 'Lys-27' thereby specifically repressing genes that promote the differentiation into non-neuronal cell lineages. As a tumor suppressor, it regulates the expression of genes involved in cell proliferation and differentiation [,
]. CHD5 is almost exclusively expressed in brain and testis. It probably regulates histone hyperacetylation and the replacement of histones by transition proteins in chromatin, being required for spermatogenesis and chromatin condensation []. CHD5 plays a role in the development of the nervous system [,
,
]. This domain represents the DEAH-box helicase domain which contains the ATP-binding region.
Baculovirus polyhedron envelope protein PEP, C-terminal
Type:
Domain
Description:
Polyhedra are large crystalline occlusion bodies containing nucleopolyhedrovirus virions, and surrounded by an electron-dense structure called the polyhedron envelope or polyhedron calyx. The polyhedron envelope (associated) protein PEP is thought to be an integral part of the polyhedron envelope. PEP is concentrated at the surface of polyhedra, and is thought to be important for the proper formation of the periphery of polyhedra. It is thought that PEP may stabilise polyhedra and protect them from fusion or aggregation [
].
Baculovirus polyhedron envelope protein PEP, N-terminal
Type:
Domain
Description:
Polyhedra are large crystalline occlusion bodies containing nucleopolyhedrovirus virions, and surrounded by an electron-dense structure called the polyhedron envelope or polyhedron calyx. The polyhedron envelope (associated) protein PEP is thought to be an integral part of the polyhedron envelope. PEP is concentrated at the surface of polyhedra, and is thought to be important for the proper formation of the periphery of polyhedra. It is thought that PEP may stabilise polyhedra and protect them from fusion or aggregation [
].
Nucleolar pre-ribosomal-associated protein 1, C-terminal domain
Type:
Domain
Description:
Nucleolar pre-ribosomal-associated protein 1 (Npa1) is required for ribosome biogenesis and operates in the same functional environment as Rsa3p and Dbp6p during early maturation of 60S ribosomal subunits [
]. The protein partners of Npa1p include eight putative helicases as well as the novel Npa2p factor. Npa1p can also associate with a subset of H/ACA and C/D small nucleolar RNPs (snoRNPs) involved in the chemical modification of residues in the vicinity of the peptidyl transferase centre [
]. The protein has also been referred to as Urb1.This domain is found towards the C terminus of Npa1.
Two-component sensor protein CpxA, periplasmic domain
Type:
Domain
Description:
The Cpx system is one of extracytoplasmic stress response systems (ESR) found in Gram-negative bacteria. ESRs are operated by a two-component signaling system which consists of a sensory histidine kinase (HK) and a response regulator (RR) as basal elements. In the Cpx system, CpxA is the inner membrane-spanning, sensory HK [
].This entry represents the periplasmic domain (also known as the VpCpxA-peri domain) of Vibrio parahaemolyticus CpxA. The VpCpxA-peri domain possesses a PAS fold that play a role in sensing envelope stress signals [
]. It recognises KCl and RbCl (Matilla et. al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043).
Interleukin-1 receptor-associated kinase 1-binding protein 1
Type:
Family
Description:
Interleukin-1 receptor-associated kinase 1-binding protein 1 (IRAK1BP1, also known as SIMPL) was originally identified in a yeast two-hybrid screen system [
]. In mice, IRAK1BP1 inhibits inflammation by promoting nuclear translocation of NF-kappaB p50 []. In Haliotis diversicolor, IRAK1BP1 plays an important role in the adult abalone immune system and might be essential in embryo and larval development in abalone [].
Cytoplasmic tRNA 2-thiolation protein 1, C-terminal
Type:
Domain
Description:
This entry represents the C-terminal zinc-ribbon domain of cytoplasmic tRNA adenylyltransferase 1 (CTU1, NCS6), a protein required for uridine thiolation of Gln, Lys, and Glu tRNAs [
]. CTU1 also carries an ATP-binding domain towards the N terminus.
Mtr2 is a monomeric, dual-action, RNA-shuttle protein found in yeasts. Transport across the nuclear-cytoplasmic membrane is via the macro-molecular membrane-spanning nuclear pore complex, NPC. The pore is lined by a subset of NPC members called nucleoporins that present FG (Phe-Gly) receptors, characteristically GLFG and FXFG motifs, for shuttling RNAs and proteins. RNA cargo is bound to soluble transport proteins (nuclear export factors) such as Mex67 in yeasts, and TAP in metazoa, which pass along the pore by binding to successive FG receptors. Mtr2 when bound to Mex67 maximises this FG-binding. Mtr2 also acts independently of Mex67 in transporting the large ribosomal RNA subunit through the pore [
].
V(D)J recombination-activating protein 1, Zinc finger
Type:
Domain
Description:
The development of B and T cells depends on the rearrangement of variable (V),
diversity (D), and joining (J) gene segments to produce mature Ig and T cellreceptor coding regions. This rearrangement process, known as V(D)J
recombination is initiated by the complex, multi-domain proteins RAG1 andRAG2. The RAG proteins catalyze DNA cleavage in the first phase of the
reaction using a recombination signal sequence (RSS) that flanks V, D and Jsegments [
,
,
].RAG1 contains a zinc-binding dimerization domain immediately N-terminal to the
catalytic core region, which in turn contains a putative DNA-binding domain at its N terminus. The dimerization domain consists of azinc C3HC4 RING finger and a C2H2 zinc RAG1-type finger.The C2H2 RAG1-type zinc finger contains the hallmarks of a classical zinc
finger structure with a two stranded β-sheet and an α-helix [].
Centromere protein Cenp-F, leucine-rich repeat-containing domain
Type:
Domain
Description:
Cenp-F, a centromeric kinetochore, microtubule-binding protein consisting of two 1,600-amino acid-long coils, is essential for the full functioning of the mitotic checkpoint pathway [
,
]. There are several leucine-rich repeats along the sequence of LEK1 that are considered to be zippers, though they do not appear to be binding DNA directly in this instance [].
Isocyanide synthase/Spore wall maturation protein DIT1
Type:
Family
Description:
Isocyanide synthases are required for the biosynthesis of isocyanides (or isonitriles), a class of microbial secondary metabolites that can be cytotoxic, antibacterial, and antiprotozoal [
].L-tyrosine isonitrile synthase from the Gammaproteobacteria Xenorhabdus nematophila participates in the biosynthesis of rhabduscin, a tyrosine derivative which is a potent inhibitor of phenoloxidase, a key component of the insect's innate immune system [
]. L-tryptophan isonitrile synthase AmbI1/2 from the Cyanobacteria Fischerella ambigua is involved in the biosynthesis of ambiguines, a family of hapalindole-type alkaloids [
]. This entry also includes Spore wall maturation protein DIT1 from Saccharomyces cerevisiae is involved in the synthesis of dityrosine [
]. Dityrosine is a sporulation-specific component of the Saccharomyces cerevisiae ascospore wall that is essential for the resistance of the spores to adverse environmental conditions. is involved in the biosynthesis of pyoverdine [
].
A family of a vain specific viral glycoproteins that forms a receptor-binding Gp95 polypeptide that is linked through disulphide to a membrane-spanning gp37 spike. Gp95 confers a high degree of subgroup specificity for interaction with distinct cell receptors [
].
Lantibiotics are peptide antimicrobials characterized by the unique amino acids lanthionine and methyllanthionine, which are introduced by dehydration of Ser/Thr residues and linkage of the resulting dehydrated amino acids with Cys residues. Members of this family are known generally as LanM, a multifunctional enzyme of lantibiotic biosynthesis [
]. This catalysis by LanM distinguishes the type 2 lantibiotics, such as lacticin 481, mersacidin, cinnamycin, and lichenicidin, from LanBC-produced type 1 lantibiotics such as nisin and subtilin.The N-terminal domain of LanM enzymes contains regions associated with Ser and Thr dehydration [
]. The C-terminal region is a LanC-type domain () that catalyses the formation of the lanthionine bridge [
]. In most lantibiotic-producing bacteria LanM modifies only a single lantibiotic precursor peptide. However, marine Prochlorococcus and Synechococcus contain multiple lantipeptide precursor lanA-like genes but only a single lanM-like gene [
].
SAS4 is a fungal silencing regulator. In S. cerevisiae, Sas4 is a subunit of a histone acetyltransferase complex termed SAS complex, which consists of Sas2, Sas4 and Sas5 [
]. The SAS complex acetylates both free histones and nucleosomes and is involved in transcriptional silencing. Both Sas4 and Sas5 are required for optimal Sas2 histone acetyltransferase activity []. This entry represents a domain found in Sas4 (something about silencing protein 4).
Charcot-Marie-Tooth disease type 1A (CMT1A) is the most common inherited peripheral neuropathy and one of the best-characterised examples of a submicroscopic genomic disorder. In most cases it is due to a submicroscopic duplication of the 1.4-Mb genomic region in chromosome band 17p12. This putative protein represents the product of transcript 4 in this region [
].
This entry represents the PX domain found in Rho GTPase-activating protein 32 (ARHGAP32, also known as RICS). RICS is a Rho GTPase-activating protein for cdc42 and Rac1. It is implicated in the regulation of postsynaptic signaling and neurite outgrowth. An N-terminal splicing variant of RICS containing additional PX and Src Homology 3 (SH3) domains, also called PX-RICS, is the main isoform expressed during neural development. PX-RICS is involved in neural functions including axon and dendrite extension, postnatal remodeling, and fine-tuning of neural circuits during early brain development [
]. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction []. The PX domain of PX-RICS specifically binds phosphatidylinositol 3-phosphate (PI3P), PI4P, and PI5P [].
Rhamnose ABC transporter, substrate-binding protein RhaS
Type:
Family
Description:
This sugar-binding component of ABC transporter complexes is found in rhamnose catabolism operon contexts. Mutation of the gene in Rhizobium leguminosarum [
] abolishes rhamnose transport and prevents growth on rhamnose as a carbon source.Bacterial high affinity transport systems are involved in active transport of solutes across the cytoplasmic membrane. Most of the bacterial ABC (ATP-binding cassette) importers are composed of one or two transmembrane permease proteins, one or two nucleotide-binding proteins and a highly specific periplasmic solute-binding protein. In Gram-negative bacteria the solute-binding proteins are dissolved in the periplasm, while in archaea and Gram-positive bacteria, their solute-binding proteins are membrane-anchored lipoproteins [
,
].
This superfamily corresponds to the structure of the second of the two 6-stranded beta barrels which comprise MreC, a rod shape-determining protein in E.coli. More generally, it is involved in cell shape determination of bacteria even when they are not rod shaped.
This superfamily corresponds to the structure of the first of the two 6-stranded beta barrels which comprise MreC, a rod shape-determining protein in E.coli. More generally, it is involved in cell shape determination of bacteria even when they are not rod shaped.
NKG2D is an activating receptor for triggering the NK cell cytotoxic activity [
]. It binds to a variety of cell surface glycoproteins distantly related to MHC class I molecules, termed NKG2D ligands (NKG2DL). The expression of a certain ligand or a particular allelic variant is essential to drive a proper immune response []. The NKG2D/NKG2DL axis has been shown to be the potential therapeutic candidate for anticancer immunotherapy [,
].
This family consists of general secretion pathway protein L sequences from several Gram-negative bacteria. GspL is predicted to contain a large cytoplasmic domain and has been shown to interact with the autophosphorylating cytoplasmic membrane protein GspE. It is thought that the tri-molecular complex of GspL, GspE and GspM might be involved in regulating the opening and closing of the secretion pore and/or transducing energy to the site of outer membrane translocation [
].The type II secretion system (T2SS) is one of several extracellular secretion systems in gram-negative bacteria. It delivers toxins and a range of hydrolytic enzymes including proteases, lipases and carbohydrate-active enzymes to the cell surface or extracellular space [
]. T2SS systems are composed of 11 to 15 different proteins, which are generally called GspA to GspO and GspS. The T2SS spans the two bacterial membranes and ensures secretion of folded proteins across the outer membrane pore formed by GspD. The inner membrane complex contains GspC, GspL, GspM, and GspF. The cytoplasmic domains of GspL and GspF interact with an ATPase, GspE. GspE is thought to energize the formation of a short pseudopilus by several pilin-like proteins, GspG to GspK []. GspD has been shown to interact with the inner membrane component GspC []. The T2SS pseudopilus is a periplasmic filament composed of the major pseudopilin, EpsG, and four minor pseudopilins, EpsH, EpsI, EpsJ and EpsK. Pseudopilus is assembled by the polymerization of GspG (also known as PulG) subunits. Pseudopilin proteins have a conserved N-terminal hydrophobic segment followed by a more variable C-terminal periplasmic and globular domain [
].
Coenzyme PQQ biosynthesis protein E is required for the biosynthesis of pyrrolo-quinoline-quinone (coenzyme PQQ). PqqE is also known as PqqA peptide cyclase, as it carries out, in conjunction with PqqD, the radical-mediated formation of a new carbon-carbon bond between two amino acid side chains on PqqA [
].
