Mitochondrial distribution and morphology family 33, fungi
Type:
Family
Description:
Members of this family are mitochondrial inner membrane proteins with a role in inner mitochondrial membrane organisation and biogenesis [
]. The yeast Mdm33 protein assembles into an oligomeric complex in the inner membrane where it performs homotypic protein-protein interactions. It has been suggested that Mdm33 plays a distinct role, possibly involved in fission of the mitochondrial inner membrane [].
This family from eukaryotes includes the chibby proteins and spermatid-associated protein (Spert). Chibby proteins inhibit the wingless/Wnt pathway by binding to beta-catenin and inhibiting beta-catenin-mediated transcriptional activation. Chibby is Japanese for small, and is named after the RNAi phenotype seen in Drosophila [
]. Spermatid-associated protein is expressed in the flower-like structure in spermatids and its function is unclear [].
This domain is found in Drosophila headcase protein [
] and the human headcase protein homologue. Drosophila headcase protein is involved in dendrite pruning [] and is a branching inhibitor during tracheal development []. It also promotes cell survival and niche maintenance in the Drosophila testis []. Human headcase protein may play an important role in human carcinogenesis [,
].
This family includes proteins from Poxvirus, such as Protein J1, a late protein which is a part of a large complex required for early virion morphogenesis. This complex participates in the formation of virosomes and the incorporation of virosomal contents into nascent immature virions. J1 protein is important for DNA packaging during immature virions (IV) formation [
,
,
].
This entry represents a family of prokaryotic aminoacyl-transferases, specifically aspartate/glutamate leucyltransferase.Aspartate/glutamate leucyltransferase (also known as bacterial protein transferase or Bpt) functions in the N-end rule pathway of protein degradation where it conjugates Leu from its aminoacyl-tRNA to the N-termini of proteins containing an N-terminal aspartate or glutamate. This protein shows sequence similarity to the eukaryotic N-end rule pathway component arginyl-transferase Ate1 [
].
A widespread family of GTP-binding proteins has been recently characterised
[,
]. The function of the proteins that belong to this family is not yet known. They are polypeptides of about 40 to 48kDa which contain the five small sequenceelements characteristic of GTP-binding proteins [
]. As a signature pattern wasselected the region that correspond to the ATP/GTP B motif (also called G-3 in
GTP-binding proteins).
This entry represents the C-terminal domain of GCF2 its homologues [
,
], as well as in a number of other proteins including Tuftelin-interacting protein 11 []. While the function of the domain is unknown, some of the proteins it is found in are reported to be involved in pre-mRNA splicing [,
]. This domain is also found in Sip1, a septin interacting protein [].
This entry represents a conserved domain found in a group of proteins called telomere-length regulation TEL2, or clock abnormal protein-2, which are conserved from plants to humans. These proteins regulate telomere length and contribute to silencing of sub-telomeric regions [
]. Tel2 acts at an early step of the TEL1/ATM pathway of DNA damage signaling []. In vitro the protein binds to telomeric DNA repeats.
Quinolinate synthetase catalyses the second step of the
de novobiosynthetic pathway of pyridine nucleotide formation. In particular, quinolinate synthetase is involved in the condensation of dihydroxyacetone phosphate and iminoaspartate to form quinolinic acid [
]. This synthesis requires two enzymes, an FAD-containing "B protein"and an "A protein". B protein converts L-aspartate to iminoaspartate. The A protein, NadA, converts iminoaspartate to quinolate. NadA harbours a [4Fe-4S] cluster [].
This domain of about 100 residues is found multiple (up to 35) copies in long proteins from several species of Vibrio, Colwellia, Bradyrhizobium, and Shewanella (hence the name VCBS) and in smaller copy numbers in proteins from several other bacteria. The large protein size and repeat copy numbers, species distribution, and suggested activities of several member proteins suggests a role for this domain in adhesion.
Proteins in this entry form a distinct group of helix-turn-helix proteins, which are strictly bacterial and nearly always shorter than 110 amino acids. They include the characterised member HigA, without which the killer protein HigB cannot be cloned. The hig (host inhibition of growth) system is noted to be unusual in that killer protein is encoded by the upstream member of the gene pair [
].
This LDXXLDAYM region (where X is any amino acid) is duplicated in the C terminus of chromatin target of PRMT1 protein (also known as Fop), which are chromatin-associated proteins that co-localise with facultative heterochromatin and are critical for oestrogen-dependent gene activation [
]. The region also occurs in other proteins, including THO complex subunit 4 (
) and RNA and export factor-binding protein 2 (
).
Members of this entry are encoded by genes in chlamydiaphage such as Vp3. These viruses have around eight genes and infect obligately intracellular bacterial pathogens of the genus Chlamydia. This protein is annotated as VP3 or structural protein (as if a protein of mature viral particles), however, it is displaced from procapsids as DNA is packaged, and therefore is more correctly described as a scaffolding protein.
Proteins containing this domain includes Methanocaldococcus jannaschii 7,8-dihydropterin-6-methyl-4-(beta-D-ribofuranosyl)-aminobenzene-5'-phosphate synthase (EC 2.5.1.15), a folate biosynthetic enzyme also known as dihydropteroate synthase and 7,8 dihydropteroate synthase [
]. Proteins containing this domain also include Thermoanaerobacter tengcongensis Tflp, which is a ferredoxin-like protein []. These proteins belong to the MBL-fold metallo-hydrolase superfamily which is comprised mainly of hydrolytic enzymes which carry out a variety of biological functions [].
This entry represents TrbL, a protein, which is encoded in the trb locus of Agrobacterium Ti plasmids where it is involved in the type IV secretion system for plasmid conjugative transfer [
,
]. TrbL is a homologue of the F-type TraG protein (which is believed to be a mating pair stabilisation pore-forming protein,
) as well as the vir system VirB6 protein [
].
This family of proteins has so far been found in three archaeal species: Methanothermobacter thermautotrophicus (Methanobacterium thermoformicicum), Methanocaldococcus jannaschii (Methanococcus jannaschii), and Archaeoglobus fulgidus. Proteins are homologous to phosphoribosylformimino-5-aminoimidazole carboxamide ribotide isomerase (HisA) and, with lower similarity, to the cyclase HisF, both of which are enzymes of histidine biosynthesis. Each species with this protein also encodes HisA. However, the function of proteins in this group is unknown.
This entry represents a family of proteins specific to the African swine fever virus (ASFV) known as the 110 family [
]. Proteins in this group are responsible for the redistribution of lumenal ER protein to an enlarged ERGIC compartment []. They contain a central cysteine rich region with eight conserved cysteines. Some proteins in this entry contain two copies of the cysteine rich region (e.g. ).
Triphosphoribosyl-dephospho-CoA is transferred to, and becomes the prosthetic group of, the respective acyl carrier protein subunits of both citrate lyase and malonate decarboxylase. Members of this protein family are triphosphoribosyl-dephospho-CoA synthases specifically from citrate lyase systems [
,
]. CitG sometimes occurs as a fusion protein with CitX. CitX transfers the prosthetic group 2'-(5''-triphosphoribosyl)-3'-dephospho-CoA to the citrate lyase gamma chain, an acyl carrier protein.
This family of proteins represents IPI from bacteriophage T4. This protein is a nuclease inhibitor which is injected by T4 to protect its DNA from gmrS/gmrD CT of pathogenic Escherichia coli into the infected host [
]. The structure of this protein consists of two small β-sheets flanked by N and C termini by α-helices. The protein has a gmrS/gmrD hydrophobic binding site [].
EF hands are helix-loop-helix binding motifs involved in the regulation of many cellular processes. EF hands usually bind to Ca2+ ions, which cause a major conformational change that allows the protein to interact with its designated targets. This protein corresponds to an EF hand which has partially or entirely lost its calcium-binding properties. The calcium insensitive EF hand is still able to mediate protein-protein recognition [
].
This entry represents the RNA recognition motif 1 (RRM1) of RBM14.RBM14 (also known as CoAA) is a heterogeneous nuclear ribonucleoprotein (hnRNP)-like protein identified as an activator of the receptor coactivator TRBP (thyroid-hormone-receptor-binding protein) [
]. It also regulates mRNA splicing and transcription []. RBM14 is a suppressor of ectopic assembly of centriolar protein complexes []. It contains two N-terminal RNA recognition motifs (RRMs) and a TRBP-interacting domain.
This entry represents the RNA recognition motif 2 (RRM2) of RBM14.RBM14 (also known as CoAA) is a heterogeneous nuclear ribonucleoprotein (hnRNP)-like protein identified as an activator of the receptor coactivator TRBP (thyroid-hormone-receptor-binding protein) [
]. It also regulates mRNA splicing and transcription []. RBM14 is a suppressor of ectopic assembly of centriolar protein complexes []. It contains two N-terminal RNA recognition motifs (RRMs) and a TRBP-interacting domain.
Elafin is an elastase inhibitor. It contains a flat core and a flexible N-terminal extremity, the three-dimensional structure is formed by a central twisted β-hairpin accompanied by two external segments linked by the proteinase binding loop [
]. This superfamily describes the C-terminal four-disulphide core or Whey Acidic Protein (WAP) domain, which harbours a functional motif involved in binding of proteinases and possibly other proteins [].
Anillin is a protein involved in septin organisation during cell division. It is an actin binding protein that is localised to the cleavage furrow, and it maintains the localisation of active myosin, which ensures the spatial control of concerted contraction during cytokinesis [
].This entry represents a conserved domain found in anillin and anillin-like proteins. This domain shares homology with the RhoA binding protein Rhotekin [
].
SOCS family proteins form part of a classical negative feedback system that regulates cytokine signal transduction. SOCS4 (Suppressor of cytokine signalling 4) is the substrate-recognition component of a SCF-like ECS (Elongin BC-CUL2/5-SOCS-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins [
]. SOCS4 and SOCS5 regulate epidermal growth factor receptor signaling [].This entry represents the SH3 domain of SOCS4.
This helical domain is found at the N-terminal of plant E3-ligase proteins, including PP2CA INTERACTING RING FINGER PROTEIN 2 (PIR2, also known as MND1-interacting protein 1) and its paralogues RF4 and RF298 from Arabidopsis. The function of this domain is unknown. PIR2 is the closest homologue of PIR1 (PP2CA interacting RING finger protein 1) and both positively modulate ABA signaling by targeting PP2CA for degradation [
].
This family consists of several membrane-associated protein VP24 sequences from a variety of Ebola viruses, as well as Lake Victoria marburgvirus. The VP24 protein of Ebola virus sp. is believed to be a secondary matrix protein and minor component of virions. VP24 possesses structural features commonly associated with viral matrix proteins and that VP24 may have a role in virus assembly and budding [
].
This family consists of several Cytomegalovirus UL84 proteins. The open reading frame UL84 of human cytomegalovirus encodes a multifunctional regulatory protein which is required for viral DNA replication and binds with high affinity to the immediate-early transactivator IE2-p86 [
]. This protein interacts with DNA sequences in oriLyt containing several CCAAT/enhancer binding protein (C/EBPα) transcription factor binding sites, which is essential for its amplification [].
This entry represents a domain found in cyclin-dependent kinase inhibitor 3 or kinase associated phosphatase proteins from several mammalian species. The cyclin-dependent kinase (Cdk)-associated protein phosphatase (KAP) is a human dual specificity protein phosphatase that dephosphorylates Cdk2 on threonine 160 in a cyclin-dependent manner [
,
]. This domain is also found in MAP kinase phosphatase and esterases.This entry contains both eukaryotic and bacterial proteins.
This entry represents a domain found at the N-terminal end of platelet-binding glycoprotein from Streptococcus sanguinis (SrpA), Streptococcal hemagglutinin from Streptococcus gordonii (Hsa) and other proteins from Firmicutes and Actinobacteria. These proteins are involved in hemagglutination and adherence to ghst glycoproteins [
]. This entry includes a Thr-Arg motif conserved across homologous carbohydrate-binding adhesins that may orient the sialic acid moiety of carbohydrate ligands [].
This entry represents a short N-terminal domain at the start of small glutamine-rich tetratricopeptide repeat-containing protein (SGTA), a heat-shock protein (HSP) co-chaperone involved in the targeting of tail-anchor membrane proteins to the endoplasmic reticulum. This is the homodimerisation domain that mediates the association with a single copy of Get4 or Get5 proteins, providing a link to the rest of the GET pathway [
].
This entry represents the C-terminal domain of the translation machinery-associated protein 46 (Tma46), a binding partner for the highly conserved developmentally regulated GTP-binding (DRG) GTPases. The interaction between Tma46 and Rbg1 GTPase (a DRG protein) modulates the function of the GTPase [
]. This domain is also found in ZC3H15 (zinc finger CCCH domain-containing protein 15), also known as DFRP1 (DRG family regulatory protein 1) [].
This entry includes transcription-associated protein 1 (Tra1) from yeast and TRRAP from mammals. Budding yeast Tra1 is a subunit of SAGA and NuA4 histone acetyltransferase complexes [
,
]. Human TRRAP is an adapter protein found in various multiprotein chromatin complexes with histone acetyltransferase activity (HAT) [].This entry represents part of the Tra1 protein composed of α-solenoid repeats that form a ring region [
].
The spike structure of bacteriophage PRD1 is comprised of proteins P2, P5, and P31. P5 is an elongated multidomain trimer. The C-terminal fragment of P5 appears to contain the residues responsible for the trimerization of the protein, whereas the smaller N-terminal part mediates the interaction with protein P31 [
,
].This domain is found at the N terminus of bacteriophage PRD1 spike protein P5.
Small acid-soluble spore protein, thioredoxin-like
Type:
Family
Description:
This protein family is restricted to a subset of endospore-forming bacteria such as Bacillus subtilis, all of which are in the Firmicutes (low-GC Gram-positive) lineage. Although previously designated tlp (thioredoxin-like protein), the B. subtilis protein was shown to be a minor small acid-soluble spore protein SASP, unique to spores. The motif E[VIL]XDE near the C terminus probably represents at a germination protease cleavage site.
Pyridine nucleotide-disulphide oxidoreductase family protein, N-terminal
Type:
Domain
Description:
Members of this entry include the N-terminal sequence regions of (probable) bifunctional proteins whose C-terminal sequences are SelD (selenide, water dikinase) the selenium donor protein necessary for selenium incorporation into protein (as selenocysteine), tRNA (as 2-selenouridine), or both. However, some members of this family occur in species that do not show selenium incorporation, and the function of this protein in these species is unknown.
This entry represents a small (about 30 amino acids), hydrophobic, moderately conserved transmembrane helix-containing region. It is found once per protein, but in many proteins per genome in several bacteria of the order Myxococcales. The region begins with a signature Gly-Cys motif; other features, including a hydrophobic transmembrane helix, Arg-rich cluster, and its location at the protein C terminus, resemble the PEP-CTERM proposed protein targeting domain.
This entry represents the SAM (sterile alpha motif) domain repeat 1 of liprin-alpha. Liprin-alpha proteins contain three copies (repeats) of the SAM domain, which is a protein-protein interaction domain. They may form heterodimers with liprin-beta proteins through their SAM domains. They participate in mammary gland development and in axon guidance; in particular, liprin-alpha is involved in formation of the presynaptic active zone [
,
].
This entry represents archaeal Nre proteins. While most archaeal organisms encode only a single Nre protein, some encode two, NreA and NreB.NreA is an archaeal PCNA interacting protein that works together with the UvrABC proteins in repairing DNA damage resulting from exposure to DNA damaging agent MMC. NreA contains a putative PIP motif at its C terminus that is important for its function [
].
This family contains lipoproteins from the Lyme disease spirochete Borrelia burgdorferi and related bacteria, including proteins from Paralogous family 54 (PFam54) and 60 (PFam60). The first crystal structure of B. burgdorferi PFam54 member BBA68 revealed a previously unseen novel fold, which, according to the CATH protein domain classification, was named the Bbcrasp-1 fold because of the common name used for the protein BBA68 [
,
].
This entry represents the central region of the E3 ubiquitin-protein ligase RNF220 [
]. RNF220 also interacts with beta-catenin independently of its E3 ligase activity; instead of ubiquitinating and destabilising it, RNF220 promotes beta-catenin stabilisation and canonical Wnt signaling []. Proteins containing this domain also include Drosophila Tey protein and some uncharacterised fungal proteins. Tey (Teyrha-Meyhra) is a transcription factor that suppresses Toll expression [].
This entry represents a NifS-like cysteine desulfurase, similar to the NifS protein of nitrogen-fixing bacteria, found almost exclusively within the epsilon division of the Proteobacteria. Like NifS, and unlike IscS, this protein is found as part of a system of just two proteins, a cysteine desulfurase and a scaffold, for iron-sulphur cluster biosynthesis. This protein is often annotated as NifS [
], so this designation was used.
This entry represents the member A of the E2/UBC superfamily of proteins found in several bacteria. The active site residues are very similar to the eukaryotic E2 proteins [
,
]. Members of this family are usually fused to E1 and JAB domains C-terminal to the E2 domain. The protein is usually in the gene neighbourhood of a gene encoding a distinct metallobetalactamase family protein [].
The vesicular integral protein of 36kDa (VIP36) is a type 1 transmembrane protein of the mammalian early secretory pathway that acts as a cargo receptor transporting high mannose type glycoproteins between the Golgi and the endoplasmic reticulum (ER) [
,
]. Lectins of the early secretory pathway are involved in the selective transport of newly synthesized glycoproteins from the ER to the ER-Golgi intermediate compartment (ERGIC) [].
This superfamily represents the TraM protein. TraM is a DNA-binding protein, encoded by plasmid DNA. TraM forms active tetramers to bridge the origin of transfer of the plasmid (oriT) to a TraD pore (a coupling protein) [
]. As such, TraM is essential for conjugative transfer of DNA between bacteria.Structurally, the DNA binding domain of the TraM protein is globular and dominantly helical [
].
This entry represents a group of eukaryotic proteins that are approximately 480 amino acids in length. FAM124 belongs to the Vicinial Oxygen Chelatase (VOC) superfamily of proteins and is comprised of two tandem alpha/beta domains, which might be enzymatic. Certain FAM124 domains fused to the TRADD-N domain are predicted to have secondarily lost their enzymatic activity and might be involved in protein-protein interactions [
].
Glycylpeptide N-tetradecanoyltransferase, also known as Myristoyl-CoA:protein N-myristoyltransferase (
) (Nmt), is the enzyme responsible for transferring a myristate group on the N-terminal glycine of a number of cellular eukaryotics and viral proteins [
]. Nmt is a monomeric protein of about 50 to 60kDa whose sequence appears to be well conserved. In Drosophila, this protein is critical for the developmental processes that involve cell shape changes and movement [].
The soluble ligand-binding β-grasp domain (SLBB) contains a β-grasp fold. They are found in a diverse set of proteins that include the animal vitamin B12 uptake proteins; transcobalamin, intrinsic factor and the bacterial polysaccharide export proteins [
]. Some proteins may be part of a membrane complex involved in electron transport, others are probably involved in the export of the extracellular polysaccharide colanic acid from the cell to medium.
Proteins of the Ca2+:Cation Antiporter (CaCA) family are found ubiquitously, having been identified in animals, plants, yeast, archaea and widely divergent bacteria. All of the characterised animal proteins catalyze Ca2+:Na+ exchange although some also transport K+. The NCX1 plasma membrane protein exchanges 3 Na+ for 1 Ca2+. The Escherichia coli ChaA protein catalyses Ca2+:H+ antiport but may also catalyze Na+:H+ antiport. All remaining well-characterised members of the family catalyze Ca2+:H+ exchange.
This entry represents the central domain found in the eukaryotic targeting protein for Xklp2 (TPX2) protein. TPX2 is a microtubule-associated protein that targets a plus end-directed motor (Xklp2) to the minus ends of microtubules in the mitotic spindle. This domain is close to the C-terminal of TPX2. The protein importin alpha regulates the activity of TPX2 by binding to the nuclear localisation signal in this domain [
].
The ThiI protein of Escherichia coli is a bifunctional protein in which most of the length of the protein is responsible for sulfurtransferase activity in 4-thiouridine modification to tRNA (
). This rhodanese-like C-terminal domain, by itself, is able to synthesize the thiazole moiety during thiamin biosynthesis [
]. Note that the invariant Cys residue in this domain is unusual in being required for both activities of the bifunctional ThiI protein.
The KOW domain of the KIN17 protein contributes to the RNA-binding properties of the whole protein. The KOW domain is known as an RNA-binding motif that is shared so far among some families of ribosomal proteins, the essential bacterial transcriptional elongation factor NusG, the eukaryotic chromatin elongation factor Spt5, the higher eukaryotic KIN17 proteins and Mtr4 [
]. KIN17 has functions in DNA replication, DNA repair and cell cycle control [].
Proteins in this entry include the sporulation protein YpeB from Bacillus subtilis. YpeB and the spore-cortex-lytic enzyme SleB are required for normal germination [
]. These proteins are restricted to endospore-forming species in the Firmicutes lineage of bacteria, and have been found in all such species to date except Clostridium perfringens. This protein is essential in stabilising SleB enzyme in Bacillus spores and may regulate its activity during spore germination [].
This entry represents the C-terminal region of the internal protein I (IpI) from bacteriophage T4. This protein is a nuclease inhibitor which is injected by T4 to protect its DNA from gmrS/gmrD CT of pathogenic Escherichia coli into the infected host [
]. The structure of this protein consists of two small β-sheets flanked by N and C termini by α-helices. The protein has a gmrS/gmrD hydrophobic binding site [].
Proteins in this family are multi-pass membrane proteins including SPEC3 and Stum. The Stum protein was identified in Drosophila and has orthologues in animals ranging from nematodes to mammals. It is required for transduction of mechanical stimuli [
].Purple sea urchin SPEC3 was found at the cilia and Golgi complexes of embryonic ectoderm cells. It has been suggested that this protein involves in ectodermal ciliogenesis [
,
].
The domain contains 8 conserved cysteines that may bind to zinc. In S. pombe, proteins containing the domain act as protein linkers, which link the chromatin modifying CLRC complex to RNAi by tethering it to the RITS complex. This domain has a slightly different arrangement of its CxxC pairs from the LIM domain, hence it is not part of that family [
]. The tandem zinc-finger structure could mediate protein-protein interactions.
Members of this protein family are predicted lipoproteins, exclusive to the Bacteroidetes phylum (previously Cytophaga-Flavobacteria-Bacteroides). Members include GldH, a protein linked to a type of rapid surface gliding motility found in certain Bacteroidetes, such as Cytophaga johnsonae (Flavobacterium johnsoniae) and Cytophaga hutchinsonii [
]. Gliding motility appears closely linked to chitin utilization in the model species C. johnsonae. Not all Bacteroidetes with members of this protein family may have gliding motility.
Members of this protein family are the FliI protein of bacterial flagellum systems. This protein acts to drive protein export for flagellar biosynthesis [
]. The most closely related family is the YscN family of bacterial type III secretion systems. This model represents one (of three) segment of the FliI family tree. These have been modeled separately in order to exclude the type III secretion ATPases more effectively.
The YneA protein is responsible for cell division suppression during the SOS response in Bacillus subtilis. Localization of the FtsZ protein to the cell division site was reduced in dinR-disrupted or yneA-expressing cells, further suggesting that the YneA protein suppresses cell division through the suppression of FtsZ ring formation. Interestingly, the B. subtilis YneA protein is structurally and phylogenetically unrelated to its functional counterpart in Escherichia coli, SulA [] (see ).
This family includes mammalian retrotransposon-derived proteins from the Mart family: LDOC1/Mart7, LDOC1L/Mart6, RTL1/Mart1, PEG10/Mart2, FAM127/Cxx1/Mart8, ZCCHC5/Mart3, Zcchc16/Mart4, RGAG4/Mart5 [
,
] and related retrotransposon Gag-like proteins. Sirh7/LDOC1 (sushi-ichi retrotransposon homologue 7/leucine zipper, downregulated in cancer 1), also known as mammalian retrotransposon-derived 7 (Mart7), is one of these newly acquired genes from long terminal repeat (LTR) retrotransposons in mammals []. This family also includes retrotransposon Gag-like proteins and uncharacterised proteins from fungi.
This entry represents a group of animal proteins that includes the human protein ACTMAP (actin maturation protease, also known as C19orf54), its homologues from vertebrates, and the orthologue protein CG33108 from Drosophila melanogaster. ACTMAP is responsible for the noncanonical excision of the acetylated methionine of actin molecules after translation. It seems to have a crucial effect in all cell types [
]. This protein family was previously known as UPF0692.
This entry represents the N-terminal SH3 domain found in the Saccharomyces cerevisiae protein Mti1 (Myosin tail region-interacting protein, also known as bbc1) and similar proteins. Mti1 interacts with and regulates type I myosins in yeast, Myo3 and Myo5, which are involved in actin cytoskeletal reorganization [
]. It also binds and inhibits Las17, a WASp family protein that functions as an activator of the Arp2/3 complex [,
].
This entry represents a region of about 41 amino acids found in a number of small proteins in a wide range of bacteria. The region usually begins with the initiator Met and contains two CxxC motifs separated by 17 amino acids. One protein in this entry has been noted as a putative regulatory protein, designated FmdB [
]. Most proteins in this entry have a C-terminal region containing highly degenerate sequence.
Arterivirus such as porcine reproductive and respiratory syndrome virus (PRRSV) contain four glycoproteins on the virion envelope: the major glycoprotein GP5 and minor glycoproteins GP2a, GP3, and GP4. GP5, previously known as Gl, is encoded in ORF5 and is 30- 45kDa in size [
]. Gl is heterogeneously glycosylated with N-acetyllactosamine in a cell-type-specific manner. It is the most abundant envelope glycoprotein and a key target for neutralising antibodies [,
].
The PX domain of Ypt35 binds to phosphatidylinositol 3-phosphate (PI3P). It also serves as a protein interaction domain, binding to the Yip1 protein family members, which localize to the ER and Golgi. Ypt35 is mainly associated with endosomes and together with Yip1p proteins, may be involved in a specific function in the endocytic pathway [
]. Ypt35 recruits the lipid transfer protein VPS13 to endosomal and vacuolar membranes [].
This region is found at the N terminus of the TRC8 protein (
). TRC8 is an E3 ubiquitin-protein ligase also known as RNF139. This region contains 12 transmembrane domains and has been suggested to contain a sterol sensing domain [
]. It has been found that TRC8 protein levels are sterol responsive and that it binds and stimulates ubiquitylation of the endoplasmic reticulum anchor protein INSIG [].
MIEF1-MP, also called alternative mitochondrial elongation factor 1 (MIEF1) protein (AltMIEF1), or MIEF1 upstream open reading frame protein, is involved in the regulation of mitochondrial fission mediated by dynamin-1-like protein (DNM1L). It positively regulates mitochondrial translation [
]. MIEF1-MP belongs to the Complex1_LYR-like superfamily that consists of proteins of diverse functions that are exclusively found in eukaryotes and contain the conserved tripeptide 'LYR' close to the N terminus.
G-protein metallochaperones ensure fidelity during cofactor assembly for a variety of metalloproteins, including adenosylcobalamin (AdoCbl)-dependent methylmalonyl-CoA mutase. IcmF is a natural fusion protein of AdoCbl-dependent isobutyryl-CoA mutase and its corresponding G-protein chaperone [
]. It exhibits both GTPase activity and AdoCbl-dependent isomerase activity, interconverting isobutyryl-CoA and n-butyryl-CoA. It can also interconvert pivalyl-CoA and isovaleryl-CoA, albeit with low efficiency, which has biotechnological potential [,
]. IcmF structure has been reported [,
].
The RuvB protein makes up part of the RuvABC revolvasome which catalyses the resolution of Holliday junctions that arise during genetic recombination and DNA repair. Branch migration is catalysed by the RuvB protein that is targeted to the Holliday junction by the structure specific RuvA protein [
]. This entry consists of the C-terminal region of the RuvB protein which is thought to be an helicase DNA-binding domain.
STAND proteins are signal transducing ATPases which undergo ligand-induced oligomerisation. Stand proteins typically feature an N-terminal effector domain, a central nucleotide-binding domain (NACHT) and a C-terminal ligand-binding region that is composed of several leucine-rich repeats (LRRs) [
]. Homology modelling predicts that the N-terminal region of NWD2, a STAND protein, adopts a HET-s-like fold. This entry represents the N-terminal domain on various fungal STAND proteins. Its function is not known [].
This domain is active in transferring the phophopantetheine prosthetic group to its attachment site on enzymes and carrier proteins. Many members of the family containing this domain are small proteins that act on the acyl carrier protein involved in fatty acid biosynthesis [
]. Some members are domains of larger proteins involved in specialised pathways for the synthesis of unusual molecules including polyketides, atypical fatty acids, and antibiotics.
This entry contains serine peptidases belonging to MEROPS peptidase family S68 (PIDD auto-processing protein, clan S-). These proteins are known as Pidd (short for p53-induced protein with a death domain) proteins [
]. Pidd forms a complex with Raidd and procaspase-2 that is known as the 'Piddosome'. The Piddosome forms when DNA damage occurs and either activates NF-kappaB, leading to cell survival, or caspase-2, which leads to apoptosis [,
].
The MOB kinase activator family includes MOB1, an essential Saccharomyces cerevisiae protein, identified from a two-hybrid screen, that binds Mps1p, a protein kinase essential for spindle pole body duplication and mitotic checkpoint regulation. Conditional alleles of MOB1 cause a late nuclear division arrest at restrictive temperature [
]. This family also includes the MOB-like protein phocein, an intracellular protein that interacts with striatin and may play a role in membrane trafficking [].
The Nop domain is present in various pre-RNA processing ribonucleoproteins (RNP):Eukaryotic Prp31, part of a tri-snRNP complex. It is involved in pre-mRNA
splicing.Eukaryotic Nucleolar proteins 56 and 58 (Nop56 and Nop58), components of
box C/D small nucleolar ribonucleoprotein (snoRNP) particles.Archaeal Nop5, an homologue of Nop56/Nop58.The Nop domain is a RNP binding module, exhibiting RNA and protein binding surfaces. It is oval-shaped and exclusively α-helical [
,
].This entry represents the Nop domain.
This family consists of various potassium transport proteins (Trk) and V-type sodium ATP synthase subunit J or translocating ATPase J (
). These proteins are involved in active sodium uptake utilizing ATP in the process. TrkH from Escherichia coli is a hydrophobic membrane protein and determines the specificity and kinetics of cation transport by the TrK system in this organism [
,
]. This protein interacts with TrkA and requires TrkE for transport activity [].
The ubiquinol-cytochrome C reductase complex (cytochrome bc1 complex) is a respiratory multi-enzyme complex [
], which recognises a mitochondrial targeting presequence. The bc1 complex contains 11 subunits: 3 respiratory subunits (cytochrome b, cytochrome c1 and Rieske protein), 2 core proteins and 6 low molecular weight proteins. This family represents the 9.5kDa subunit of the complex, known as subunit 8 or protein QP-C []. This subunit together with cytochrome B binds to ubiquinone.
The WWE domain is named after three of its conserved residues and is predicted to mediate specific protein-protein interactions in ubiquitin and ADP ribose conjugation systems. This domain is found as a tandem repeat at the N-terminal of Deltex, a cytosolic effector of Notch signalling thought to bind the N-terminal of the Notch receptor [
]. It is also found as an interaction module in protein ubiquination and ADP ribosylation proteins [].
Members of this family are zinc metallopeptidases with a range of specificities. The peptidase family M23 is included in this family, these are Gly-Gly endopeptidases. Peptidase family M23 are also endopeptidases. This family also includes some bacterial lipoproteins. This family also includes leukocyte cell-derived chemotaxin 2 (LECT2) proteins. LECT2 is a liver-specific protein which is thought to be linked to hepatocyte growth although the exact function of this protein is unknown [
,
].
This entry represents the steroidogenic acute regulatory protein (StAR)-related lipid transfer (START) domain of STARD2 (also known as phosphatidylcholine transfer protein/PC-TP) and related proteins [
]. STARD2 is a cytosolic phosphatidycholine (PtdCho) transfer protein, which traffics PtdCho, the most common class of phospholipids in eukaryotes, between membranes. It represents a minimal START domain structure. STARD2 plays roles in hepatic cholesterol metabolism, in the development of atherosclerosis, and may have a mitochondrial function [].
Flaviviruses are small enveloped viruses with virions comprised of three proteins called C, M and E [
,
,
]. The envelope glycoprotein M is made as a precursor, called prM. The precursor portion of the protein is the signal peptide for the proteins entry into the membrane. prM is cleaved to form M in a late-stage cleavage event. Associated with this cleavage is a change in the infectivity and fusion activity of the virus.
This entry represents a strictly archaeal putative protein-sorting motif, PGF-CTERM. It is the (predicted) recognition sequence for an exosortase homologue, archaeosortase. In some archaea, up to fifty proteins have this domain as their C-terminal region, usually preceded by a Thr-rich region likely to be heavily glycosylated. The removal of this sorting signal may be associated with a C-terminal prenyl group modification in the halobacterial major cell surface glycoprotein, an S-layer protein [
].
This entry includes Drosophila Orai and human Orai1, Orai2 and Orai3. ORAI-1 green fluorescent protein (GFP) reporters are co-expressed with STIM-1 (ER CA(2+) sensors) in the gonad and intestine. The protein has four predicted transmembrane domains with a highly conserved region between TM2 ad TM3. This conserved domain is thought to function in channel regulation. ORAI1-related proteins are required for the production of the calcium channel, CRAC, along with STIM1-related proteins [
].
This N-terminal homology domain appears to be a specialised class of signal peptide. It occurs mostly in the halophilic archaea, primarily on proteins with the C-terminal PGF-CTERM domain, including the S-layer-forming major surface glycoprotein of several species. The PGF-CTERM domain is the putative archaeosortase A recognition sequence. However, this N-terminal domain occurs also in several archaeal proteins that lack PGF-CTERM, and occurs in bacteria on a protein from Clostridium leptum DSM 753.
Flaviviruses are small enveloped viruses with virions comprised of three proteins called C, M and E [
,
,
]. The envelope glycoprotein M is made as a precursor, called prM. The precursor portion of the protein is the signal peptide for the proteins entry into the membrane. prM is cleaved to form M in a late-stage cleavage event. Associated with this cleavage is a change in the infectivity and fusion activity of the virus.
This entry represents the Nop domain superfamily.The Nop domain is present in various pre-RNA processing ribonucleoproteins (RNP):Eukaryotic Prp31, part of a tri-snRNP complex. It is involved in pre-mRNA
splicing.Eukaryotic Nucleolar proteins 56 and 58 (Nop56 and Nop58), components of
box C/D small nucleolar ribonucleoprotein (snoRNP) particles.Archaeal Nop5, an homologue of Nop56/Nop58.The Nop domain is a RNP binding module, exhibiting RNA and protein binding surfaces. It is oval-shaped and exclusively α-helical [
,
].
This entry consists of a group of proteins predominantly found in Firmicutes, including Uncharacterized protein YfhH from Bacillus subtilis and protein GK0453 from Geobacillus kaustophilus. GK0453 shows two small domains: an helix-turn-helix like motif is found in its N-terminal domain while an SH3-like β-barrel like structure is observed its C-terminal region. Its specific function is unknown [
]. Some of the members of this protein family are annotated as being transcriptional regulators (see ,
).
Members of the HesA/MoeB/ThiF family of proteins (
) include a number of members encoded in the midst of thiamine biosynthetic operons. This mix of known and putative ThiF proteins shows a deep split in phylogenetic trees. The Escherichia coli ThiF and MoeB proteins are seemingly more closely related than the E. coli ThiF and Campylobacter (for example) ThiF. This entry represents the more widely distributed clade of ThiF proteins as found in E. coli.
The ubiquinol-cytochrome C reductase complex (cytochrome bc1 complex) is a respiratory multi-enzyme complex [
], which recognises a mitochondrial targeting presequence. The bc1 complex contains 11 subunits: 3 respiratory subunits (cytochrome b, cytochrome c1 and Rieske protein), 2 core proteins and 6 low molecular weight proteins. This entry represents the 9.5kDa subunit of the complex, known as subunit 8 or protein QP-C []. This subunit together with cytochrome B binds to ubiquinone.
This entry is represented by Bacteriophage P2, GpM. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches.This family consists of several phage small terminase subunit proteins as well as some related bacterial sequences [
]. M protein is probably an endonuclease which directs cos cleavage. The Q, P and M proteins are needed to package DNA into proheads and for the conversion of proheads to capsids.
Members of this protein family are ABC transporter permease subunits as identified by
, but additionally contain the Actinobacterial insert domain described by
. Some homologues (lacking the insert) have been described as transporters of manganese or of chelated iron. Members of this family typically are found along with an ATP-binding cassette protein, a permease, and an LPXTG-anchored protein with two or three copies of the
insert that occurs just once in this protein family.
NifZ is a short protein is found in the nif (nitrogen fixation) operon. It is required for the maturation of the nitrogenase MoFe protein.
In the absence of NifZ, only one of the two P-clusters of the MoFe protein is matured to the ultimate [8Fe-7S]structure. The other P-cluster site in the protein contains a [4Fe-4S] cluster pair, suggesting that NifZ is specifically required for the formation of the second P-cluster [,
,
].
The SNF1-related protein kinase 1 (SnRK1) is a heterotrimeric eukaryotic kinase that interacts with diverse proteins and regulates their activity in response to starvation and stress signals. This entry represents a group of plant FCS-Like Zinc finger proteins, including FLZ8 and MARD1 from Arabidopsis. They may act as an adapter to facilitate the interaction of SnRK1 complex with effector proteins, conferring tissue- and stimulus-type specific differences in the SnRK1 regulation pathway [
,
].
Beta-barrel outer membrane proteins (OMP) rely on Omp85-like proteins for insertion into the outer membrane. The targeting signal for Omp85 is usually found in the C terminus of OMPs, and the target sequences differ somewhat by species. Observations in Escherichia coli mutant PhoE protein and neisserial OMPs suggest that there are alternative, less-efficient recognition sites in the protein that mediate binding to Omp85 [
].This entry represents a targeting signal for outer membrane insertion.
This entry contains proteins that have the C-terminal domain of a family of multiple membrane-spanning proteins of Gram-positive bacteria. One member was shown to be a host protein essential for phage infection, so many members of this family are called "phage infection protein". A separate model,
, represents the conserved N-terminal domain. The domains are separated by regions highly variable in both length and sequence, often containing extended heptad repeats as described in
.
This domain is found at the C terminus of proteins of the CbbQ/NirQ/NorQ family of proteins which play a role in the post-translational activation of Rubisco [
]. It is also found in the Thauera aromaticaTutH protein which is similar to the CbbQ/NirQ/NorQ family [], as well as in putative chaperones. The ATPase domain associated with various cellular activities (AAA) is found in the same bacterial and archaeal proteins as the domain described here.
The ospA and ospB genes encode the major outer membrane proteins of the Lyme disease spirochaete Borrelia burgdorferi [
]. The deduced gene products OspA and OspB, contain 273 and 296 residues respectively []. The two Osp proteins show a high degree of sequence similarity, indicating a recent evolutionary event. Molecular analysis and sequence comparison of OspA and OspB with other proteins has revealed similarity to the signal peptides of prokaryotic lipoproteins [,
].
PRE-mRNA splicing is catalysed by the spliceosome, a large dynamic complex composed of five small nuclear RNAs (snRNAs) and more than 80 proteins. Brr1 (Bad Response to Refrigeration protein 1) is a component of spliceosomal snRNPs [
]. Brr1 is a nuclear protein involved in mRNA splicing and required for snRNA accumulation and snRNP biogenesis [,
,
]. It interacts with histone protein HTA1 and associates with the spliceosome during snRNA and snRNP production [].
This entry represents RNA dependent RNA polymerases found in several types of viruses [
], especially those with a tripartite genome (RNA1, RNA2 and RNA3) and an encapsidated subgenomic RNA (RNA4) from which the coat protein is expressed, such as Cucumber mosaic virus (strain NT9) (CMV). This entry contains the following proteins:Viral RNA-directed RNA polymerase 2A (protein 2A) [
].Putative RNA dependent RNA polymerase from Tobacco mosaic virus [].Non structural polyprotein from Togavirus [
].
The N-terminal YSIRK signal domain targets proteins to the cross-wall, or septum, of dividing Gram-positive bacteria. Lipoprotein signal motifs direct a characteristic N-terminal cleavage and lipid modification for membrane anchoring. This Streptococcal-only signal peptide variant appears to be a hybrid between the two, likely directing protein targeting of nascent surface lipoproteins to the cross-wall. Nearly all members of this family have the characteristic LPXTG cell wall anchor signal at the C terminus.
This family includes UL25 proteins from human cytomelagovirus (HCMV), as well as U14 proteins from the human herpesviruses HHV-6 and HHV-7. These 85kDa phosphoproteins appear to act as structural antigens, but their precise function is otherwise unknown. This entry also includes protein M35 from Murid herpesvirus 1. M35 is released by murine cytomegalovirus immediately upon infection in order to deftly inhibit the antiviral type I IFN response by targeting NF-kappaB-mediated transcription [
].
