Nuclear receptor-interacting protein 1, repression domain 4
Type:
Domain
Description:
Nuclear receptor-interacting protein 1 (also known as nuclear factor RIP140) modulates transcriptional activation by steroid receptors such as NR3C1, NR3C2 and ESR1 [
]. It also modulates transcriptional repression by nuclear hormone receptors [] and clock gene expression []. It consists of four distinct autonomous repression domains [].This domain is the fourth (C-terminal) repression domain of nuclear receptor-interacting protein 1 [
,
].
Nuclear receptor-interacting protein 1, repression domain 3
Type:
Family
Description:
Nuclear receptor-interacting protein 1 (also known as nuclear factor RIP140) modulates transcriptional activation by steroid receptors such as NR3C1, NR3C2 and ESR1 [
]. It also modulates transcriptional repression by nuclear hormone receptors [] and clock gene expression []. It consists of four distinct autonomous repression domains [].This domain is the third repression domain of nuclear receptor-interacting protein 1 [
,
].
Nuclear receptor-interacting protein 1, repression domain 2
Type:
Domain
Description:
Nuclear receptor-interacting protein 1 (also known as nuclear factor RIP140) modulates transcriptional activation by steroid receptors such as NR3C1, NR3C2 and ESR1 [
]. It also modulates transcriptional repression by nuclear hormone receptors [] and clock gene expression []. It consists of four distinct autonomous repression domains [].This domain is the second repression domain of nuclear receptor-interacting protein 1 [
,
].
Nuclear receptor-interacting protein 1, repression domain 1
Type:
Domain
Description:
Nuclear receptor-interacting protein 1 (also known as nuclear factor RIP140) modulates transcriptional activation by steroid receptors such as NR3C1, NR3C2 and ESR1 [
]. It also modulates transcriptional repression by nuclear hormone receptors [] and clock gene expression []. It consists of four distinct autonomous repression domains [].This domain is the first (N-terminal) repression domain of nuclear receptor-interacting protein 1 [
,
].
Restriction of telomere capping protein 4, C-terminal
Type:
Domain
Description:
This entry represents the C-terminal domain of the RTC4 (restriction of telomere capping protein 4) protein from yeasts. In Saccharomyces cerevisiae, deletion of RTC4 affects the cell response to telomere uncapping [
]. This domain is also found in proteins that contain a DNA-binding myb domain.
ESX-1 to ESX-5 gene clusters encode proteins that are either secreted or building blocks of the actinobacterial Type 7 secretion system (T7SS) [
]. In Mycobacterium tuberculosis ESX-1 is responsible for secretion of important virulence factors such as EsxA and EsxB as well as other virulence-associated proteins, ESX-3 is involved in metal acquisition being critical for mycobacterial survival. ESX-5 is also important for the secretion of members of the PE/PPE family of proteins that play a role in virulence and cell wall integrity. The function of ESX-2 and ESX-4 is still unknown although ESX-4 seems to be the ancestral system from which ESX systems have evolved. All ESX gene clusters contain three or four ESX conserved components (Ecc), named EccB, EccC, and EccD, with EccE being present in all ESX systems, except of ESX-4. EccC is a member of the FtsK/SpoIIIE-like ATPase family and provides the energy to transport proteins across the mycobacterial membrane; EccB and EccE have N-terminal transmembrane elements and large C-terminal regions predicted to be localised in the periplasm, but their function, molecular function or interacting partners remain unknown. EccD contains an N-terminal cytoplasmic domain followed by 11 predicted transmembrane helices, which is thought to form a cytoplasmic membrane channel through which the proteins are secreted [].This entry represents the EccD family of proteins, which includes EccD1-5. EccD1, also known as Snm4, has a ubiquitin-like fold and forms a dimer, with a negatively charged groove which indicates that it likely interacts with positive charged partners and may recruit other T7SS components or secretion substrates or it may form a gating element to close the channel during inactive periods. The residues forming the negatively charged groove are not conserved in EccD1 homologs from other ESX systems, suggesting that they have a system-specific role. It is responsible for multiple suppressive effects on macrophages and required for bacterial replication after phagocytosis [
,
].
Flagellar filament outer layer protein FlaA, Spirochaetes
Type:
Family
Description:
Periplasmic flagella are the organelles of spirochete mobility, and are structurally different from the flagella of other motile bacteria. They reside inside the cell within the periplasmic space, and confer mobility in viscous gel-like media such as connective tissue [
]. The flagella are composed of an outer sheath of FlaA proteins and a core filament of FlaB proteins. Each species usually has several FlaA protein species [].
Putative abortive phage resistance protein AbiGii toxin
Type:
Family
Description:
This is a family of putative type IV toxin-antitoxin system toxins. The AbiG abortive phage resistance protein affects lactococcal bacteriophages phiP335 and phiQ30 but not the other P335 phage species. AbiGii toxin appears to confer resistance to phages by a mechanism of abortive infection that acts by interfering with phage RNA synthesis [
]. The cognate anti-toxin is found in ().
Conserved hypothetical protein CHP03883, F420 biosynthesis associated
Type:
Family
Description:
This entry represents proteins found in coenzyme F420 biosynthesizing species of the Actinobacterial, Chloroflexi and Archaeal lineages. The few organisms having genes within this family and lacking F420 biosynthesis may either have an undiscovered F420 transporter, or may represent F420-to-FMN revertants. This family includes a Chloroflexus Aurantiacus protein whose crystal structure has been determined. This has been annotated as a putative hydrolase, but there is currently no supporting evidence for this. There is no cofactor present in the structure.
Cell division control protein 4, dimerisation domain
Type:
Domain
Description:
This is the dimerisation domain (D domain) of fungal cell division control protein 4 (Cdc4) [
]. Budding yeast Cdc4 is a substrate recognition component of a SCF (SKP1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex which mediates the ubiquitination and subsequent proteasomal degradation of target proteins [].
LKB1 serine/threonine kinase interacting protein 1, N-terminal
Type:
Domain
Description:
This domain represents the N terminus of LIP1, a leucine-rich-repeat protein that interacts with kinase LKB1/STK11, implicated in Peutz-Jeghers syndrome. LIP1 (LKB1 serine/threonine kinase interacting protein 1), also known as STK11IP, interacts with the TGF-beta-regulated transcription factor SMAD4 to form a LKB1-LIP1-SMAD4 ternary complex. Mutations in SMAD4 lead to juvenile polyposis, suggesting a mechanistic link between these two diseases [
,
].
Mannosyl phosphorylinositol ceramide synthase regulatory protein Csg2
Type:
Family
Description:
Csg2 is an integral membrane protein with up to 10 transmembrane segments that, when over-expressed, localises to the endoplasmic reticulum [
,
]. It regulates mannosyl phosphorylinositol ceramide synthase and is thereby implicated in calcium homoeostasis in the cell [].
This entry includes protein 1 found in association with tubulins epsilon and delta complex. This complex is required for centriole maintenance and it has been demonstrated that it is a component of several ciliary structures. It acts as a positive regulator of ciliary hedgehog signalling which plays key roles in embryonic development and in cancers [
]. Additionally, this protein may play a role in counteracting perturbation of actin filaments, such as after treatment with the actin depolymerising microbial metabolite Chivosazole F [
].
CusB can be divided into four different domains. The first three domains of the protein are mostly β-strands. However, the fourth domain forms an all α-helical domain, which is folded into a three-helix bundle secondary structure [
]. This entry represents the first beta-domain (domain 1) of cation efflux system protein CusB from E. coli. It is formed by the N and C-terminal ends of the polypeptide (residues 89-102 and 324-385) [
]. CusB is part of the copper-transporting efflux system CusCFBA []. This domain can also be found in other membrane-fusion proteins, such as HlyD, MdtN, MdtE and AaeA. HlyD is a component of the prototypical alpha-haemolysin (HlyA) bacterial type I secretion system, along with the other components HlyB and TolC. HlyD and HlyB are inner-membrane proteins and specific components of the transport apparatus of alpha-haemolysin. HlyD is anchored in the cytoplasmic membrane by a single transmembrane domain and has a large periplasmic domain within the carboxy-terminal 100 amino acids []. HlyB and HlyD form a stable complex that binds the recombinant protein bearing a C-terminal HlyA signal sequence and ATP in the cytoplasm []. HlyD, HlyB and TolC combine to form the three-component ABC transporter complex that forms a trans-membrane channel or pore through which HlyA can be transferred directly to the extracellular medium. Cutinase has been shown to be transported effectively through this pore [].
DENN domain-containing protein 5B, second RUN domain
Type:
Domain
Description:
This entry represents the second RUN domain of DENND5B and similar proteins from vertebrates.
This entry includes DENN domain-containing protein 5B (DENND5B, also called Rab6-interacting protein 1 (Rab6IP1)-like protein) which functions in membrane trafficking at a crossroads between the Golgi and the endosomal system []. It is composed of an N-terminal DENN domain () followed by two RUN domains flanking a PLAT domain (
) [
].
DENN domain-containing protein 5B, first RUN domain
Type:
Domain
Description:
This entry represents the first RUN domain of DENND5B and similar proteins from vertebrates.
This entry includes DENN domain-containing protein 5B (DENND5B, also called Rab6-interacting protein 1 (Rab6IP1)-like protein) which functions in membrane trafficking at a crossroads between the Golgi and the endosomal system []. It is composed of an N-terminal DENN domain () followed by two RUN domains flanking a PLAT domain (
) [
].
DENN domain-containing protein 5A, first RUN domain
Type:
Domain
Description:
This entry represents the first RUN domain of DENND5A and similar proteins from vertebrates. This domain is required for Rab6-dependent recruitment of DENND5A on Golgi membranes [
]
DENND5A, also called Rab6-interacting protein 1 (Rab6IP1), is present predominantly in developing neuronal tissue, and functions in membrane trafficking at a crossroads between the Golgi and the endosomal system. It is a guanine nucleotide exchange factor (GEFs) that binds Rab6 and Rab11A in their GTP-bound conformation [,
]. It is composed of an N-terminal DENN domain () followed by two RUN domains flanking a PLAT domain (
) [
,
,
,
,
,
,
,
,
,
].
DENN domain-containing protein 5A, second RUN domain
Type:
Domain
Description:
This entry represents the second RUN domain of DENND5A and similar proteins from vertebrates.
DENND5A, also called Rab6-interacting protein 1 (Rab6IP1), is present predominantly in developing neuronal tissue, and functions in membrane trafficking at a crossroads between the Golgi and the endosomal system. It is a guanine nucleotide exchange factor (GEFs) that binds Rab6 and Rab11A in their GTP-bound conformation [,
]. It is composed of an N-terminal DENN domain () followed by two RUN domains flanking a PLAT domain (
) [
,
,
,
,
,
,
,
,
,
].
This is a family of predicted membrane glycoproteins from fungi. Proteins in this family include the yeast plasma membrane H+-ATPase Pma1. It is the major regulator of cytoplasmic pH and plasma membrane potential and the most abundant protein in the plasma membrane [
]. Exp1 (ER eXport of Pma1) and Psg1 (Pma1 Stabilization in the Golgi) are involved in Pma1 maturation process [].
DNA replication complex GINS protein SLD5, C-terminal
Type:
Domain
Description:
DNA replication complex GINS protein SLD5 is a component of the GINS tetrameric protein complex, which is involved in both initiation and elongation stages of eukaryotic chromosome replication [
,
,
,
]. It is essential for the maintenance of genomic integrity, GINS plays a central role in coordinating DNA replication with cell cycle checkpoints and is involved in cell growth. It has been associated with NK cell deficiency and neutropenia [,
,
].This entry represents the C-terminal domain of SLD5. This region is important in the assembly of the GINS complex.
T6SS bacteria employ toxic effectors to inhibit rival cells and concurrently use effector cognate immunity proteins to protect their sibling cells. The effector and immunity pairs (E-I pairs) endow the bacteria with a great advantage in niche competition. This is the C-terminal domain of Tli4. The Tle cognate immunity proteins (Tlis) can directly disable the transported Tle protein and thereby mediate the self-protection process. The Tle-Tli effector-immunity (E-I) pairs confer substantial advantage to the donor cell during interbacterial competition. Tli4 displays a two-domain structure, in which a large lobe and a small lobe form a crab claw-like conformation. Tli4 uses this crab claw to grasp the cap domain of Tle4, especially the lid2 region, which prevents the interfacial activation of Tle4 and thus causes enzymatic dysfunction of Tle4. Structural comparison indicates similarity between this C-terminal domain of Tli4 and Tsi3, which is the cognate immunity protein of the effector protein Tse3 in P. aeruginosa PDB:4n7s [
].
Toxin co-regulated pilus biosynthesis protein Q, C-terminal
Type:
Domain
Description:
The toxin-coregulated pilus (TCP) of Vibrio cholerae and the soluble TcpF protein that is secreted via the TCP biogenesis apparatus are essential for intestinal colonisation in the disease of cholera. TCP fibres are homopolymers of TcpA pilin, encoded by the first gene in the tcp biogenesis operon. TcpQ is part of an outer membrane complex of the TCP biogenesis apparatus, comprised of TcpC and TcpQ. TcpQ is required for proper localisation of TcpC to the outer membrane [
,
]. This entry represents a C-terminal domain found in TcpQ and other pilus biosynthesis proteins.
Alginate biosynthesis sensor protein KinB, sensor domain
Type:
Domain
Description:
This entry reprsents the N-terminal sensor domain of histidine kinase from Pseudomonas species. The domain is the extracellular sensing domain with four helical bundle [
,
]. It recognises inorganic phosphate (Matilla et. al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043).
This entry represents the type III secretion protein EspD. The pathogenesis of enteropathogenic Escherichia coli (EPEC) involves the translocation of effector proteins by the type III secretion system into the host cell, including translocated intimin receptor (Tir) and several E. coli secreted proteins (Esp). Secretion of virulence proteins of EPEC is tightly regulated. CesD is the type III chaperone for the translocator proteins EspB and EspD [
]. The translocation of virulence proteins into host cells results in attaching and effacing (A/E) lesions, actin rearrangements and pedestal formation []. The translocator and effector proteins facilitate colonization of the mucosal surface of the intestine via formation of attaching and effacing (A/E) lesions.
Secretion of virulence factors in Gram-negative bacteria involves transportation of the protein across two membranes to reach the cell exterior [
]. There have been four secretion systems described in animal enteropathogens, such as Salmonella and Yersinia, with further
sequence similarities in plant pathogens like Ralstonia and Erwinia.The type III secretion system is of great interest, as it is used to transport virulence factors from the pathogen directly into the host cell [
] and is only triggered when the bacterium comes into close contact with the host. The protein subunits of the system are very similar to those of bacterial flagellar biosynthesis. However, while the latter forms aring structure to allow secretion of flagellin and is an integral part of
the flagellum itself [], type III subunits in the outer membrane translocate secreted proteins through a channel-like structure.Exotoxins secreted by the type III system do not possess a secretion signal,
and are considered unique for this reason []. Certain proteobactria, including Salmonella and Shigella spp., secrete invasin protein B, which is required for internalisation of the bacterium within the host cell []. Induction of apoptosis is then carried out, by the binding of IL-1 converting enzyme to the exotoxin.This entry represents invasin protein B from various proteobacteria, including:SipB from Salmonella sp., which is required for entry into the host cell through presentation or delivery of SipC at the host cell plasma membrane. Along with SipC, SipB is necessary for the transfer of other effector proteins into the host cell. It induces macrophage apoptosis either by binding and activating the proapoptotic enzyme caspase-1 (caspase-1 dependent), resulting in the release of interleukin-1 beta active form, or by disrupting mitochondria and inducing autophagy (caspase-1 independent). The former is dependent of its membrane-fusion activity. The sipBC complex, in association with its chaperone sicA, is regulated by binding of invE [
,
,
].IpaB from Shigella sp., which forms a pore with IpaC and is inserted into the host cell membrane through the Mxi/Spa apparatus during cell contact. This pore probably allows the translocation of IpaA. IpaB has also been found to be necessary and sufficient to activate macrophage apoptosis by binding to interleukin-1 beta converting enzyme (ICE). It has also been shown to be important, along with IpaD, to block or regulate secretion through the Mxi/Spa translocon in the presence or absence of the secretion signal, respectively [
]. IpaB is secreted through the specialised type-III secretion system Mxi/Spa and is inserted into the host cell membrane. It is also secreted into the host cell cytoplasm after the escape of bacteria from phagosome, where it co-localises with ICE.BipB from Burkholderia sp., which plays a role in the bacterium-induced formation of multinucleated giant cell (MNGC), which is formed after host cell fusion, as well as in the intercellular spreading of bacteria and in the induction of apoptosis in macrophages. BipB may act in concert with other effector proteins to induce fusion of host cell membranes [
].
FERM domain-containing protein 6, FERM domain C-lobe
Type:
Domain
Description:
This entry represents the C-lobe of FERM domain found in FRMD6. The Drosophilla FRMD6 homologue, Ex, is a regulator of the Hippo/SWH (Sav/Wts/Hpo) signaling pathway, which plays a pivotal role in organ size control and is tumour suppression by restricting proliferation and promoting apoptosis [
]. However, human FRMD6 is thought to function independently of the Hippo pathway. Instead it may inhibit progression through the S phase of the cell cycle by upregulating p21(Cip1) and downregulating Cyclin A []. It has been implicated in the progression of Alzheimer disease []. FRMD6 contains a single FERM domain which has a cloverleaf tripart structure composed of: (1) FERM_N (A-lobe or F1); (2) FERM_M (B-lobe, or F2); and (3) FERM_C (C-lobeor F3). The C-lobe is a member of the PH domain superfamily. The FERM domain is found in the cytoskeletal-associated proteins such as ezrin, moesin, radixin, 4.1R, and merlin. These proteins provide a link between the membrane and cytoskeleton and are involved in signal transduction pathways. The FERM domain is also found in protein tyrosine phosphatases (PTPs) , the tyrosine kinases FAK and JAK, in addition to other proteins involved in signaling. This domain is structurally similar to the PH and PTB domains and consequently is capable of binding to both peptides and phospholipids at different sites [
,
].
ASPP1 (apoptosis-stimulating of p53 protein) is a member of the ASPP protein family (Apoptosi-Stimulating Protein of p53) that activates the p53-mediated apoptotic response. It functions as a tumour suppressor and coordinates with p53 to protect haematopoietic stem cell (HSC) pool integrity, guarding against haematological malignancies [
,
,
]. The ASPP family of proteins may be a target for cancer therapy [].This entry represents the RA domain present at the N terminus of ASSP1, which is a ubiquitin-like domain.
This domain found in PHF12 (PHD finger protein 12, also known as
Pf1) binds to the MRG domain of mortality factor 4-like protein 1 (MORF4L1, also known as MRG15) []. In mammals, the corepressor Sin3B, the histone deacetylase HDAC1, MRG15 and Pf1 form a complex that plays important roles in regulation of transcription [].
Helicobacter pylori makes use of a type IV secretion system similar in mechanism
to the conjugation machine of Agrobacterium tumefaciens []. These machinessecrete three different types of substrate: DNA conjugation intermediates,
as in A. tumefaciens; multimeric proteins such as the pertussis toxin ofBordetella pertussis; and the CagA protein of H. pylori. CagA has been
linked to the more severe forms of gastric ulcers and duodenal cancers [].Both CagA and the secretion system apparatus are encoded in the large
pathogenicity island, termed cag [], possessed by the malignant disease-causing type I bacterial strains.CagX is found on this pathogenicity island; mutants lacking the gene fail
to induce pathogenicity in an infected mouse model. CagX is thought to play a role in the process of conjugation [].
This entry represents bacterial TraL proteins. TraL is a predicted peripheral membrane protein involved in bacterial sex pilus assembly [
]. TraL is part of the type IV secretion system for conjugative plasmid transfer []. The exact function of TraL is unknown.
DNA mismatch repair protein HSM3, N-terminal domain
Type:
Domain
Description:
Hsm3 is a proteasome-dedicated chaperone that forms a base precursor, Hsm3-Rpt1-Rpt2-Rpn1 [
]. Hsm3 consists of 23 α-helices forming 11 repeats similar to the HEAT repeats. This entry includes the first 5 repeats at the N terminus.
Protein of unknown function DUF226, Borrelia species
Type:
Family
Description:
This family of proteins are found in Borrelia burgdorferi and Borrelia garinii. The proteins are about 190 amino acids long and have no known function.
Alginate biosynthesis protein AlgX, C-terminal carbohydrate-binding module
Type:
Domain
Description:
This entry represents the C-terminal domain of the alginate biosynthesis protein AlgX. This domain is a bacterial carbohydrate-binding module (CBM) frequently found at the C terminus of enzymes. The combination is not unusual as the CBMs function to bring the relevant polysaccharide into close proximity to the active site [
].
This is a family of proteins of approximately 200 residues that are conserved in fungi. Ilm1 is part of the peroxisome, a complex that is the sole site of beta-oxidation in Saccharomyces cerevisiae (Baker's yeast) and known to be required for optimal growth in the presence of fatty acid. Ilm1 may participate in the control of the C16/C18 ratio since it interacts strongly with Mga2p, a transcription factor that controls expression of Ole1, the sole fatty acyl desaturase in S. cerevisiae responsible for conversion of the saturated fatty acids stearate (C18) and palmitate (C16) to oleate and palmitoleate, respectively [
].
Mitogen-activated protein (MAP) kinase kinase kinase, MLK1-4
Type:
Family
Description:
This entry represents mitogen-activated protein kinase kinase kinase MAP3K9 (MLK1), MAP3K10 (MLK2), MAP3K11 (MLK3) and MAP3K21 (MLK4), which form part of the mixed lineage kinase (MLK) family [
].
Plasmid conjugative transfer entry exclusion protein TraS
Type:
Family
Description:
Entry exclusion (Eex) is a process which prevents redundant transfer of DNA between donor cells. TraS is a protein involved in Eex. It blocks redundant conjugative DNA synthesis and transport between donor cells, and it is suggested that TraS interferes with a signalling pathway that is required to trigger DNA transfer [
]. TraS on the recipient cell is known to form an interaction with TraG on the donor cell [].
Eukaryotic translation initiation factor 4E binding protein
Type:
Family
Description:
This entry represents a group of eIF4E binding proteins, including eIF4E transporter (eIF4E-T) from mammals, cup protein from D. melanogaster and ifet-1 from C. elegans. Protein cup functions in Smaug-mediated translational repression [
,
]. Ifet-1 is a broad-scale translational repressor in C. elegans [
,
]. eIF4E-T is the transporter protein for shuttling the mRNA cap-binding protein eIF4E protein, targeting it for nuclear import. eIF4E-T contains several key binding domains including two functional leucine-rich NESs (nuclear export signals) between residues 438-447 and 613-638 in the human protein. The other two binding domains are an eIF4E-T-binding site, between residues 27-42 in
, and a bipartite NLS (nuclear localisation signals) between 194-211, and these lie in family eIF4E-T_N. eIF4E-T is the eukaryotic translation initiation factor 4E that is the rate-limiting factor for cap-dependent translation initiation [
].
Uncharacterised protein AF_0060, NTP Pyrophosphohydrolase MazG-like domain
Type:
Domain
Description:
This domain is found in an uncharacterized protein from Archaeoglobus fulgidus (AF_0060) and its homologues from bacteria. The biological function of this protein remains unclear, however, AF_0060 shows high sequence similarity to the dimeric 2-deoxyuridine 5'-triphosphate nucleotidohydrolase (dUTP pyrophosphatase or dUTPase) and NTP-PPase MazG proteins. Members in this entry consist of a single MazG-like domain that contains a well conserved divalent ion-binding motif EXX[E/D] [].
Outer membrane lipoprotein carrier protein LolA, Proteobacteria
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 [
].
Uncharacterised conserved protein UCP011452, HNH endonuclease domain-type
Type:
Family
Description:
There is currently no experimental data for members of this group or their homologues. However, they contain a version of the HNH endonuclease domain (
).
Inactive phospholipase C-like protein 2, EF-hand domain
Type:
Domain
Description:
A group of phospholipase C-related, catalytically inactive proteins have been identified as novel inositol 1,4,5-trisphosphate binding proteins with a domain organisation similar to phospholipase C-delta, but lacking the enzymatic activity. These inactive phospholipase C-like (PLCL) proteins consists of at least two types of proteins (PLCL-1 and PLCL2).Inactive phospholipase C-like protein 1 is an inositol 1,4,5-trisphosphate binding protein with a domain organisation similar to phospholipase C-delta, but lacking the enzymatic activity. It is involved in inositol phospholipid-based intracellular signaling and it is essential for the function of GABA(A) receptors [
,
].Similar to PLCL-1, PLCL-2 may be involved in both inositol 1,4,5-trisphosphate-mediated and gamma-amino butyric acid-related signaling [
].This entry represents the EF-hand domain of PLCL-2.
KICSTOR complex protein C12orf66-like, central domain superfamily
Type:
Homologous_superfamily
Description:
This entry represents the central domain of C12orf66-like proteins. Human C12orf66 is part of the KICSTOR complex that functions in the amino acid-sensing branch of the TORC1 signaling pathway [
].
Protein-export membrane protein SecD/SecF, archaeal and bacterial
Type:
Family
Description:
Secretion across the inner membrane in some Gram-negative bacteria occurs via the preprotein translocase
pathway. Proteins are produced in the cytoplasm as precursors, and require a chaperone subunit to direct them tothe translocase component [
]. From there, the mature proteins are either targeted to the outermembrane, or remain as periplasmic proteins. The translocase protein subunits are encoded on the bacterial
chromosome. The translocase itself comprises 7 proteins, including a chaperone protein (SecB), an ATPase (SecA), an integralmembrane complex (SecCY, SecE and SecG), and two additional membrane proteins that promote the release of
the mature peptide into the periplasm (SecD and SecF) []. The chaperone protein SecB [] is a highly acidic homotetrameric protein that exists as a "dimer of dimers"in the bacterial cytoplasm.
SecB maintains preproteins in an unfolded state after translation, and targets these to the peripheral membraneprotein ATPase SecA for secretion [
]. Together with SecY and SecG, SecE forms a multimericchannel through which preproteins are translocated, using both proton motive forces and ATP-driven secretion. The
latter is mediated by SecA. The structure of theEscherichia coli SecYEG assembly revealed a sandwich of two membranes interacting through the extensive cytoplasmic
domains []. Each membrane is composed of dimers of SecYEG. The monomeric complex contains 15transmembrane helices.
The SecD and SecF equivalents of the
Gram-positive bacterium Bacillus subtilis are jointly present in one polypeptide,denoted SecDF, that is required to maintain a high capacity for protein secretion.
Unlike the SecD subunit of the pre-protein translocase of E. coli, SecDFof B. subtilis was not required for the release of a mature secretory protein from
the membrane, indicating that SecDF is involved in earlier translocation steps [].Comparison with SecD and
SecF proteins from other organisms revealed the presence of 10 conservedregions in SecDF, some of which appear to be important for SecDF function.
Interestingly, the SecDF protein of B. subtilis has 12 putative transmembranedomains. Thus, SecDF does not only show sequence similarity but also structural
similarity to secondary solute transporters [].This entry represents archaeal and bacterial SecD and SecF protein export membrane proteins and their archaeal homologues [
]. It is found in association with SecD and SecF proteins are part of the multimeric protein export complex comprising SecA, D, E, F, G, Y, and YajC [
]. SecD and SecF are required to maintain a proton motive force [].
Methionine import ATP-binding protein MetN, ATP-binding domain
Type:
Domain
Description:
MetN (also known as YusC) is an ABC-type transporter encoded by metN of the metNPQ operon in Bacillus subtilis that is involved in methionine transport. Other members of this system include the MetP permease and the MetQ substrate binding protein [
]. ABC transporters are a subset of nucleotide hydrolases that contain a signature motif, Q-loop, and H-loop/switch region, in addition to, the Walker A motif/P-loop and Walker B motif commonly found in a number of ATP- and GTP-binding and hydrolyzing proteins [].
The Arf GAPs (GTPase-activating proteins) are a family of multidomain proteins with the common function of accelerating the hydrolysis of GTP bound to Arf proteins. ASAP proteins are a subtype of Arf GAPs. ASAP3 (Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 3, also known as ACAP4, DDEFL1 (Development and Differentiation Enhancing Factor-Like 1), or centaurin beta-6), is a focal adhesion-associated Arf GAP that functions in cell migration and invasion of cancers [
,
]. It is an Arf6-specific GTPase activating protein (GAP) and is co-localized with Arf6 in ruffling membranes upon EGF stimulation []. ASAP3 promotes cell proliferation [], being implicated in the pathogenesis of hepatocellular carcinoma and plays a role in regulating cell migration and invasion [].ASAP3 (Arf-GAP with SH3 domain, ANK repeat and PH domain-containing protein 3) contains an N-terminal BAR domain, followed by a Pleckstrin homology (PH) domain, an Arf GAP domain and ankyrin (ANK) repeats. Unlike ASAP1 and ASAP2, ASAP3 do not have an SH3 domain at the C-terminal. This entry represents the N-terminal BAR domain, domains that form dimers that bind to membranes, induce membrane bending and curvature, and may also be involved in protein-protein interactions [,
,
. The BAR domain of the related protein ASAP1 mediates membrane bending, is essential for function, and auto inhibits GAP activity by interacting with the PH and/or Arf GAP domains.
In Arabidopsis, AtTPC1 mediates Ca(2+) flux and regulates germination and stomatal movement [
,
]. In tobacco cells, NtTPC1 has roles in defense responses [] and acts as the major ROS-responsive Ca2+ channel [].
Oxygenic photosynthesis uses two multi-subunit photosystems (I and II) located in the cell membranes of cyanobacteria and in the thylakoid membranes of chloroplasts in plants and algae. Photosystem II (PSII) has a P680 reaction centre containing chlorophyll 'a' that uses light energy to carry out the oxidation (splitting) of water molecules, and to produce ATP via a proton pump. Photosystem I (PSI) has a P700 reaction centre containing chlorophyll that takes the electron and associated hydrogen donated from PSII to reduce NADP+ to NADPH. Both ATP and NADPH are subsequently used in the light-independent reactions to convert carbon dioxide to glucose using the hydrogen atom extracted from water by PSII, releasing oxygen as a by-product.The photosynthetic reaction centres (RCs) of aerotolerant organisms contain a heterodimeric core, built up of two strongly homologous polypeptides each of which contributes five transmembrane peptide helices to hold a pseudo-symmetric double set of redox components. Two molecules of PscD are housed within a subunit. PscD may be involved in stabilising the PscB component since it is found to co-precipitate with FMO (Fenna-Mathews-Olson BChl a-protein) and PscB. It may also be involved in the interaction with ferredoxin [
].
Hydrogenase nickel incorporation protein HypA/HybF, conserved site
Type:
Conserved_site
Description:
Bacterial membrane-bound nickel-dependent hydrogenases require a number of accessory proteins which are involved in their maturation [
]. One of these proteins is generally known as HypA. HypA is a metallochaperone that binds nickel to bring it safely to its target. The nickel coordinates with four nitrogens within the protein. Four conserved cysteines towards the C terminus bind one zinc moiety, probably to stabilise the protein fold []. In Helicobacter pylori, HypA is involved in the maturation of both hydrogenase and urease []. Escherichia coli has two proteins that belong to this family, HypA and HybF []. A homologue, MJ0214, has also been found in a number of archaeal species, including the genome of Methanocaldococcus jannaschii (Methanococcus jannaschii).This entry represents a region from these proteins that contains two of the conserved cysteines.
A-kinase anchor protein 7, RI-RII subunit-binding domain
Type:
Domain
Description:
This entry represents the RI-RII subunit-binding domain found at the C-terminal of the cyclic AMP-dependent protein kinase A (PKA) anchor protein, AKAP7. This protein anchors PKA, for its role in regulating PKA-mediated gene transcription in both somatic cells and oocytes, by binding to its regulatory subunits, RI and RII, hence being known as a dual-specific AKAP [
]. The 25 crucial amino acids of RII-binding domains in general form structurally conserved amphipathic helices with unrelated sequences; hydrophobic amino acid residues form the backbone of the interaction and hydrogen bond- and salt-bridge-forming amino acid residues increase the affinity of the interaction []. The nuclear localisation signal-containing domain is found at the N terminus.
Protein phosphatase 1, regulatory subunit 15B, N-terminal
Type:
Domain
Description:
This entry represents the conserved N-terminal domain of the regulatory subunit (15B) of protein phosphatase 1 (also known as CReP, or the constitutive repressor of eIF2alpha phosphorylation). The CReP catalytic subunit functions in the dephosphorylation of eIF2-alpha under basal conditions in the absence of stress. In response to translation inhibition, there is reduced synthesis of the labile CReP that contributes to elevated levels of eIF2-alpha phosphorylation []. The C terminus, family PP1c, is shared with the apoptosis-associated protein Gadd34 and herpes simplex virus [].
Protein phosphatase 1, regulatory subunit 15A/B, C-terminal
Type:
Domain
Description:
This entry represents the conserved C terminus of the regulatory subunit (15A and 15B) of protein phosphatase 1. This C-terminal domain appears to be a binding region for the catalytic subunit (PP1C) of protein phosphatase-1, which may in some circumstances also be retroviral in origin since it is found in both herpes simplex virus and in mouse and man. This domain is found in Gadd-34 apoptosis-associated proteins as well as the constitutive repressor of eIF2-alpha phosphorylation/protein phosphatase 1, regulatory (inhibitor) subunit 15b, otherwise known as CReP. Diverse stressful conditions are associated with phosphorylation of the alpha-subunit of eukaryotic translation initiation factor 2 (eIF2-alpha) on serine 51. This signaling event, which is conserved from yeast to mammals, negatively regulates the guanine nucleotide exchange factor, eIF2-B and inhibits the recycling of eIF2 to its active GTP bound form. In mammalian cells eIF2-alpha phosphorylation emerges as an important event in stress signaling that impacts on gene expression at both the translational and transcriptional levels [
].
Primosomal protein N', 3' DNA-binding domain superfamily
Type:
Homologous_superfamily
Description:
Primosomal protein N', also known as ATP-dependent helicase PriA, is a component of the primosome, involved in replication, repair and recombination. PriA is a multifunctional enzyme that mediates the essential process of restarting prematurely terminated DNA replication reactions in bacteria [
,
]. PriA presents a two-domain architecture, with an N-terminal DNA-binding domain (DBD) and a C-terminal helicase domain (HD). Structural studies reveal a central helicase core surrounded by an array of DNA-binding elements. These elements include two domains within the DBD, a 3' DNA-binding domain (3'BD) and an unusual circularly permuted winged helix (WH) domain, and two domains within the HD, a Cys-rich region (CRR) that binds two Zn2+ ions and a C-terminal domain (CTD) which shows unexpected similarity to the S10 subunit of the bacterial ribosome [].This superfamily represents the 3' DNA binding domain.
F-BAR domain only protein 2 (FCHo2) belongs to the F-BAR family, whose members have been implicated in cell membrane processes such as membrane invagination, tubulation and endocytosis [
]. FCHo2 organises clathrin-coated structures and interacts with adaptor Disabled-2 for low-density lipoprotein receptor endocytosis [
,
]. The structure of the FCHo2 F-BAR domain has been solved [].This entry represents the N-terminal F-BAR (FES-CIP4 Homology and Bin/Amphiphysin/Rvs) domain of FCHo2. This domain form banana-shaped dimers with a positively-charged concave surface that binds to negatively-charged lipid membranes. These dimers can induce membrane deformation in the form of long tubules [
].
Protein phosphatase 1 regulatory subunit 35, C-terminal
Type:
Domain
Description:
This entry represents the C terminus of protein phosphatase 1 regulatory subunit 35. This protein inhibits the serine/threonine-protein phosphatase PPP1CA [
].
I-BAR domain containing protein IRSp53, Inverse-Bin/Amphiphysin/Rvs domain
Type:
Domain
Description:
IRSp53, also known as IRS-58 or BAIAP2 (brain-specific angiogenesis inhibitor 1-associated protein 2), is an I-BAR (Bin/amphipysin/Rvs) domain containing protein. BAR domain forms an anti-parallel all-helical dimer, with a curved (banana-like) shape, that promotes membrane tubulation. BAR domain proteins can be classified into three types: BAR, F-BAR and I-BAR. BAR and F-BAR proteins generate positive membrane curvature, while I-BAR proteins induce negative curvature [].IRSp53 is an adaptor protein that acts at the membrane-actin interface, coupling membrane deformation with F-actin polymerisation [
]. It is involved in the formation of filopodia and lamellipodia in cultured mesenchymal cells and contributes to assembly/maintenance of tight junctions in cultured epithelial cells []. IRSp53 contains an N-terminal I-BAR domain, followed by a partial CRIB domain and a SH3 domain. It binds to small GTPase Cdc42, Rac1 and WAVE1 []. IRSp53 binds Rac through its I-BAR domain and to WAVE through its SH3 domain, and thus contributes to membrane ruffling []. Its SH3 domain also interacts with other regulators of actin dynamics, such as WAVE2, Mena, mDia1, Dynamin1, Eps8 and N-WASP []. This protein has been associated with human breast cancer and Gilles de la Tourette syndrome [
]. This entry represents the N-terminal I-BAR domain, also known as IRSp53/MIM homology Domain (IMD), which binds and bundles actin filaments, binds membranes, and interacts with the small GTPase Rac [
].
Plasmodium falciparum erythrocyte membrane protein 1, N-terminal
Type:
Domain
Description:
This entry represents a domain found in the most variable part of the variant surface antigen family member from Plasmodium falciparum, the erythrocyte membrane protein-1 (PfEMP1) [
]. PfEMP1 is an important target for protective immunity and is implicated in the pathology of malaria through its ability to adhere to host endothelial receptors.
This entry represents the N terminus of GTSE1 proteins. GTSE-1 (G2 and S phase-expressed-1) protein is specifically expressed during S and G2 phases of the cell cycle. It is mainly localised to the microtubules and when overexpressed delays the G2 to M transition. the full protein negatively regulates p53 transactivation function, protein levels, and p53-dependent apoptosis [,
]. This domain is found in eukaryotes, and is approximately 140 amino acids in length. There is a conserved FDFD sequence motif.
Williams-Beuren syndrome chromosomal region 28 protein homologue
Type:
Family
Description:
Transmembrane protein 270, also known as WBS28, is an integral membrane protein. These proteins have been identified as being linked to Williams-Beuren syndrome, which is a neurodevelopmental and multisystemic disease that is characterised by mental retardation with unique cognitive and personality profile and multiple dysmorphic and metabolic features [
]. This family is found in eukaryotes and proteins are typically 266 amino acids in length.
This entry represents the PX domain found in ribosomal protein S6 kinase delta-1. The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others [
].Ribosomal protein S6 kinase delta-1, also known as RPK118, binds sphingosine kinase-1, a key enzyme in the synthesis of the lipid messenger sphingosine 1 phosphate (SPP). It may be involved in transmitting SPP-mediated signaling into the cell [
]. RPK118 specifically binds to phosphatidylinositol 3-phosphate []. RPK118 also binds peroxiredoxin-3 and may be involved in transporting peroxiredoxin-3 from the cytoplasm to its mitochondrial site of function via endosome trafficking []. The C terminus of RPK118 consist of a domain with conserved Ser/Thr protein kinase residues, specially resembling human ribosome protein S6 kinase [].
Autoinducer 2 ABC transporter, substrate-binding protein LsrB
Type:
Family
Description:
Autoinducers are signalling molecules secreted by bacteria to communicate with one another in a process called quorum sensing. Autoinducer 2-binding protein LsrB is part of the ABC transporter complex LsrABCD involved in autoinducer 2 (AI-2) import. It binds AI-2 and delivers it to the LsrC and LsrD permeases [
].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 [
,
].
Cattle cerebrum and skeletal muscle-specific protein 1
Type:
Family
Description:
Following a subtractive bioinformatics analysis of cattle placenta ESTs, a number of novel transcripts were identified. Gene-expression profiles and further bioinformatics analyses have indicated that the identified genes may be of evolutionary and physiological importance, with possible roles in placental adaptation [
]. Revealed by this study was so-called Cattle Cerebrum and Skeletal Muscle-Specific Transcript 1 (CCSMST1) [], whose translation product is believed to contain a signal peptide and a single transmembrane (TM) domain [].
This superfamily represents the plug domain, which consists of 6 beta strands, found
in FimD. In apo-FimD this domain sits within the translocation channel of FimD. When FimC-FimH interacts with FimD, this domain is displaced and exposes a circular channel within the translocation channel [].
Macrolide export protein MacA, alpha-hairpin domain superfamily
Type:
Homologous_superfamily
Description:
MacA is part of the MacAB-TolC complex (composed of an inner membrane transporter, MacB, a periplasmic membrane fusion protein, MacA, and an outer membrane component, TolC), which is a tripartite macrolide efflux transporter driven by hydrolysis of ATP [
]. MacA interacts with MacB and TolC []. MacA can bind rough-core lipopolysaccharide (R-LPS) specifically and with high affinity, suggesting that the complex could also transport R-LPS or a similar glycolipid []. Its protein structure has been solved [].This entry represents the α-hairpin of MacA, which is implicated to bind to TolC.
This domain is found at the N terminus of members of the general secretory system II protein E. Proteins in this subfamily are typically involved in Type IV pilus biogenesis (e.g.
), though some are involved in other processes; for instance aggregation in Myxococcus xanthus (e.g.
) [
].
Gliding motility-associated ABC transporter permease protein GldF
Type:
Family
Description:
Members of this protein family are exclusive to the Bacteroidetes phylum (previously Cytophaga-Flavobacteria-Bacteroides). GldF is believed to be a ABC transporter permease protein (along with ATP-binding subunit, GldA and a substrate-binding subunit, GldG) and is linked to a type of rapid surface gliding motility found in certain Bacteroidetes, such as Cytophaga johnsonae (Flavobacterium johnsoniae) and Cytophaga hutchinsonii. Knockouts of GldF abolish the gliding phenotype [
]. Gliding motility appears closely linked to chitin utilization in the model species C. johnsonae. Bacteroidetes with members of this protein family appear to have all of the genes associated with gliding motility.
Mitogen-activated protein (MAP) kinase kinase kinase Ssk2/Ssk22
Type:
Family
Description:
This entry includes a group of MAP kinase kinase kinase from fungi, including Ssk2/Ssk22 from budding yeasts and Win1/Wis4 from fission yeasts. They are kinases involved in a signal transduction pathway that is activated by environmental stress [
,
,
].
AlkB proteins are dioxygenases that repair alkylation damage to DNA and RNA [
]. Nine mammalian AlkB homologues exist (ALKBH1-8, FTO), but only a subset functions as DNA/RNA repair enzymes [].This entry represents AlkB homologue 3 (ALKBH3, ABH3), which has a strong preference for single-stranded DNA also demethylates 1-methyladenine (1meA) and 3-methylcytosine (3meC) in RNA [
,
,
]. ALKBH3 is overexpressed in various cancers and contributes to cancer cell survival [,
,
].
This group represents a type III secretion system apparatus protein SsaM. The product of the ssaM gene does not appear to be similar to products of other type III secretion systems [
].
Protein ACCUMULATION AND REPLICATION OF CHLOROPLASTS 6-like
Type:
Family
Description:
This family represents plant Protein ACCUMULATION AND REPLICATION OF CHLOROPLASTS 6 (ARC6) and its paralogue PARC6, components of the plastid division machinery which are essential for the chloroplast replication process [
,
]. ARC6 is evolutionarily related to the cyanobacterial cell division protein Ftn2/ZipN [], being unique to the division machineries of cyanobacteria and chloroplasts. Their sequences share about 19% identity and are quite conserved along their length. Chloroplast division implies the assembly and constriction of the tubulin-like FtsZ ring on the stromal surface of the inner envelope membrane (IEM) and the dynamin-like ARC5 ring on the cytosolic surface of the outer envelope membrane (OEM). The assembly of these structures is coordinated by a pair of paralogous proteins, ARC6 and PARC6 from the IEM, and PDV2 and PDV1 from the OEM. They contain single transmembrane (TM) domains towards their C terminus with short C-terminal regions extending into the intermembrane space (IMS) [,
,
,
,
]. Crystal structure of ARC6 showed that it comprises a chloroplast transit peptide, cleaved after chloroplast localisation, followed by a stroma-facing, a transmembrane and IMS regions. The C-terminal IMS is highly conserved in ARC6 and Ftn2 proteins [
]. ARC6 interacts with FtsZ and PDV2 through its stromal and IMS regions, respectively. ARC6-PDV2 interaction is key for PDV2 localisation to the division site and to specify the site of ARC5 recruitment []. PARC6 and PDV1 interact and function in the same way as ARC6-PDV2 [,
].This entry also includes ARC6 homologues from cyanobacteria.
Heat shock protein 70kD, peptide-binding domain superfamily
Type:
Homologous_superfamily
Description:
Members of the 70-kilodalton heat-shock protein (HSP70) family promote protein folding both constitutively and in response to stress. These proteins have two functional units: a substrate-binding unit, and an adenosine triphosphatase unit. The substrate-binding unit of DnaK consists of a β-sandwich domain followed by α-helical segments. The α-helical domain stabilises the complex, but does not contact the peptide directly [
].This superfamily represents peptide-binding β-sandwich domain from DnaK and other
HSP70 proteins.
Heat shock protein 70kD, C-terminal domain superfamily
Type:
Homologous_superfamily
Description:
Members of the 70-kilodalton heat-shock protein (HSP70) family promote protein folding both constitutively and in response to stress. These proteins have two functional units: a substrate-binding unit, and an adenosine triphosphatase unit. The substrate-binding unit of DnaK consists of a β-sandwich domain followed by α-helical segments. The α-helical domain stabilises the complex, but does not contact the peptide directly [
].This superfamily represents the C-terminal α-helical subdomain of the substrate-binding unit from DnaK and other HSP70 proteins.
[NiFe]-hydrogenase-3-type complex Eha, membrane protein EhaH, predicted
Type:
Family
Description:
This group contains membrane proteins that are predicted to be transmembrane subunits (EhaH) of multisubunit membrane-bound [NiFe]-hydrogenase Eha complexes.The energy-converting hydrogenase A (
eha) operon encodes a putative multisubunit membrane-bound [NiFe]-hydrogenase Eha in Methanobacterium thermoautotrophicum (strain Marburg / DSM 2133). Sequence analysis of the ehaoperon indicates that it encodes at least 20 proteins, including the [NiFe]-hydrogenase large subunit, the [NiFe]-hydrogenase small subunit, and two broadly conserved integral membrane proteins (one this entry). These four proteins show high sequence similarity to subunits of the Ech hydrogenase from Methanosarcina barkeri, Escherichia coli hydrogenases 3 and 4 (Hyc and Hyf), and CO-induced hydrogenase from Rhodospirillum rubrum (Coo), all of which form a distinct group of multisubunit membrane-bound [NiFe]-hydrogenases (together called hydrogenase-3-type hydrogenases). In addition to these four subunits, the ehaoperon encodes a 6[4Fe-4S] polyferredoxin, a 10[4Fe-4S]polyferredoxin, ten other predicted integral membrane proteins (
,
,
,
,
,
,
,
,
,
), and four hydrophilic subunits (
,
,
) (the latter hydrophilic subunits is a member of well-characterised enzyme family but lack the essential amino acids assumed to form the active site [
]). All of these proteins are expressed and therefore thought to be functional subunits of the Eha hydrogenase complex []. Note, however, that the ten additional predicted integral membrane proteins are absent from Ech, Coo, Hyc, and Hyf complexes (and therefore from corresponding organisms), indicating that those complexes have a simpler membrane component than Eha [].Members of this group are homologous to the N-terminal domain of EhbF, HyfF of E. coli hydrogenase 4, amongst others. Therefore, this type of membrane subunit of Eha complex is conserved across the various hydrogenase-3-type hydrogenases (that is, they are not limited to the Eha subgroup). A protein with sequence similarity to the C-terminal part of EhbF is not present in the Eha complex (not encoded by the
ehaoperon).
Based on sequence similarity and genome context analysis, other organisms such as Methanopyrus kandleri,Methanocaldococcus jannaschii, and M. thermoautotrophicum also encode Eha-like [NiFe]-hydrogenase-3-type complexes and have very similar ehaoperon structure.
The function of Kelch repeat and BTB domain-containing protein 4 (KBTBD4) is not clear. It belongs to a large family of cullin-RING ubiquitin ligase adaptors that facilitate the ubiquitination of target substrates.
Heat shock 70kDa protein 14, nucleotide-binding domain
Type:
Domain
Description:
Human HSPA14 (also known as 70kDa heat shock protein 14 or HSP70L1), is ribosome-associated and belongs to the heat shock protein 70 (HSP70) family of chaperones that assist in protein folding and assembly, and can direct incompetent 'client' proteins towards degradation. Typically, HSP70s have a nucleotide-binding domain (NBD) and a substrate-binding domain (SBD). The nucleotide sits in a deep cleft formed between the two lobes of the NBD. The two subdomains of each lobe change conformation between ATP-bound, ADP-bound, and nucleotide-free states. ATP binding opens up the substrate-binding site; substrate-binding increases the rate of ATP hydrolysis. HSP70 chaperone activity is regulated by various co-chaperones: J-domain proteins and nucleotide exchange factors (NEFs). HSPA14 interacts with the J-protein MPP11 to form the mammalian ribosome-associated complex (mRAC) [
]. HSPA14 participates in a pathway along with Nijmegen breakage syndrome 1 (NBS1, also known as p85 or nibrin), heat shock transcription factor 4b (HSF4b), and HSPA4 (belonging to a different subfamily), that induces tumor migration, invasion, and transformation []. HSPA14 is a potent T helper cell (Th1) polarizing adjuvant that contributes to antitumor immune responses [,
].
Periplasmic copper-binding protein NosD, beta helix domain
Type:
Domain
Description:
This entry represents a parallel beta helix domain found in several proteins, including NosD. NosD is a periplasmic protein which is thought to insert copper into the exported reductase apoenzyme (NosZ) [].
PHD finger protein 1 (PHF1) is a polycomb group (PcG) protein that plays a role in H3K27 methylation and Hox gene silencing [
]. The Tudor domain of human PHF1 recognises both H3K36me3 and H3tK27me3 [,
]. The interactionbetween PHF1 and H3K36me3 stabilises the nucleosome in a conformation in which the nucleosomal DNA is more accessible to DNA-binding regulatory proteins [
]. PHF1 is also involved in the response to DNA double-strand breaks [] and acts as a positive regulator of the p53 pathway [].This entry represents the first PHD finger of PHF1.
Aminoacyl tRNA synthase complex-interacting multifunctional protein 2
Type:
Family
Description:
Aminoacyl tRNA synthase complex-interacting multifunctional protein 2 (AIMP2), also known as multisynthase complex auxiliary component p38, is required for assembly and stability of the multi-tRNA synthetase complex (MSC complex) [
]. MSC is a macromolecular protein complex consisting of nine different ARSs and three ARS-interacting multifunctional proteins (AIMPs) [].
