Fanconi anemia-associated protein of 24kDa (FAAP24) plays a role in DNA repair through recruitment of the FA core complex to damaged DNA. It regulates FANCD2 monoubiquitination upon DNA damage. When repressed, it induces chromosomal instability as well as hypersensitivity to DNA cross-linking agents. It targets FANCM/FAAP24 complex to the DNA, preferentially to single strand DNA [
].Fanconi anemia (FA) is a human disorder characterized by cancer susceptibility and cellular sensitivity to DNA crosslinks and other damages. The FA complex repairs the interstrand cross-linking (ICL) lesions and coordinates activities of the downstream DNA repair pathway including nucleotide excision repair, translesion synthesis, and homologous recombination. It is required for the monoubiquitylation of FANCD2 and FANCI heterodimer. The FA core complex consists of FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL, FANCM, FANCT (UBET2), FAAP100 and FAAP24 [
,
].
This entry represents a family of uncharacterised bacterial proteins. One member,
, shows significant structural similarity to TNF-like jelly roll fold, which may indicate an immunomodulatory function [
] or a bioadhesion role [].
PRDA1 is a chloroplast nucleoid protein that is involved in the regulation of plastid gene expression and is required for early chloroplast development. It may positively regulate plastid-encoded RNA polymerase (PEP) activity through its interaction with two other proteins known to be essential for PEP-related chloroplast development, MRL7 and FSD2 [
].
Transcriptionally active chromosome (TAC) is a fraction of protein/DNA complexes with RNA polymerase activity in the plastid. It consists of the multisubunit plastid-encoded polymerase (PEP) and several non-rpo subunits. PTAC7/TAC7 is a TAC component. It has a role in regulating PEP-dependent chloroplast gene expression and chloroplast development [
].
This entry includes a group of bacterial proteins, including EipB from Brucella. EipB is a periplasmic protein that functions as part of a system required for cell envelope homeostasis. It adopts a β-spiral fold, consisting of 14 β-strands and 2 α-helices [
].
ATPase expression protein 2 (also known as ATP13 in some species) is necessary for the expression of subunit 9 of mitochondrial ATPase. The protein has a basic amino terminal signal sequence that is cleaved upon import into mitochondria [
].
Pathovars of Pseudomonas syringae interact with their plant hosts via the action of Hrp outer protein (Hop) effector proteins, injected into plant cells by the type III secretion system. The proteins are called HopJ after the original member HopPmaJ [
].
This entry represents a group of plant proteins, including OEP37 from Arabidopsis. OEP37 may constitute a novel peptide-sensitive ion channel in the outer envelope of plastids [
].
This entry is represents Phage-like element PBSX protein XkdN from Bacillus subtilis (strain 168) and similar proteins predominantly found in Firmicutes and some tailed bacteriophages. The characteristics of the protein distribution suggest prophage matches in addition to the phage matches. Members of this group of proteins are chaperones involved in phage tail assembly [
,
] and have been predicted to form a spiral structure [].
This group of proteins are functionally uncharacterised. The C terminus contains a cluster of cysteines that are similar to the iron-sulphur cluster found at the N terminus of
.
This family includes the Deinococcus DdrB protein, a ssDNA binding protein induced by ionizing radiation which has a role in genome reconstitution [
]. The structure of DdrB is known []. This family also includes some possibly distantly related cyanobacterial proteins.
This entry includes a group of bacterial proteins, including EipB from Brucella. EipB is a periplasmic protein that functions as part of a system required for cell envelope homeostasis. It adopts a β-spiral fold, consisting of 14 β-strands and 2 α-helices [
].
This entry includes a group of bacterial proteins, including EipB from Brucella. EipB is a periplasmic protein that functions as part of a system required for cell envelope homeostasis. It adopts a β-spiral fold, consisting of 14 β-strands and 2 α-helices [
].
This entry includes a group of bacterial proteins, including EipB from Brucella. EipB is a periplasmic protein that functions as part of a system required for cell envelope homeostasis. It adopts a β-spiral fold, consisting of 14 β-strands and 2 α-helices [
].
This entry includes a group of bacterial proteins, including EipB from Brucella. EipB is a periplasmic protein that functions as part of a system required for cell envelope homeostasis. It adopts a β-spiral fold, consisting of 14 β-strands and 2 α-helices [
].
This protein is also referred to as Gp7. The protein contains a DNA-binding function and may have a role in mediating the structural transition from prohead to mature virus and also scaffold release [
].Gp7 is arranged within the capsid as a series of concentric shells [].
This entry contains viral proteins that are involved in virion envelopment and egress. It includes Epstein-Barr virus (EBV) BBLF1 protein (also known as cytoplasmic envelopment protein 3 and Herpesvirus UL11 homologue), which is present in the tegument layer of EBV and is involved in virion maturation. BBLF1 also participates in viral entry at the fusion step probably by regulating the core fusion machinery. BBLF1 has been shown to localize to the trans-Golgi network along with gp350/220, a site where final envelopment of EBV particles takes place. BBLF1 shares 13 to 15% amino acid sequence identity with the herpes simplex virus 1 UL11 and cytomegalovirus UL99 tegument proteins, and like these it is a myristoylated and palmitoylated protein [
].
Fungal immunomodulatory protein FIP-Fve superfamily
Type:
Homologous_superfamily
Description:
FIP-Fve (Fungal Immunomodulatory Protein Fve) is a major fruiting body protein from Flammulina velutipes, a mushroom possessing immunomodulatory activity [
]. It stimulates lymphocyte mitogenesis, suppresses systemic anaphylaxis reactions and oedema, enhances transcription of IL-2, IFN-gamma and TNF-alpha, and haemagglutinates red blood cells. It appears to be a lectin with specificity for complex cell-surface carbohydrates. Fve adopts a tertiary structure consisting of an immunoglobulin-like β-sandwich, with seven strands arranged in two beta sheets, in a Greek-key topology. It forms a non-covalently linked homodimer containing no Cys, His or Met residues; dimerisation occurs by 3-D domain swapping of the N-terminal helices and is stabilised predominantly by hydrophobic interactions [].
This entry represents proteins of unknown function found primarily in Bacteroides species. The B. thetaiotaomicron gene appears to be upregulated in the presence of host or other bacterial species compared to growth in pure culture [
,
].
Non-structural protein NSP3, N-terminal, betacoronavirus
Type:
Domain
Description:
The multi-domain non-structural protein NSP3 is the largest protein encoded by the coronavirus (CoV) genome, with an average molecular mass of about 200 kD. While some of the domains differ between CoV genera, eight domains of NSP3 exist in all known CoVs: the ubiquitin-like domain 1 (Ubl1), the Glu-rich acidic domain (also called "hypervariable region"), a macrodomain (also named "X domain"), the ubiquitin-like domain 2 (Ubl2), the papain-like protease 2 (PL2pro), the NSP3 ectodomain (3Ecto, also called "zinc-finger domain"), as well as the domains Y1 and CoV-Y of unknown functions. There are also two transmembrane regions, TM1 and TM2, which exist in all CoVs [
].This entry corresponds to the N-terminal domain of NSP3 found in betacoronavirus. This includes the NSP3a domain which has the ubiquitin-like 1 (UB1) and glutamic acid-rich acidic (AC) hypervariable domains [
]. NSP3a interacts with numerous other proteins involved in replication and transcription and may serve as a scaffolding protein for these processes. The N-terminal NSP3a domain interacts with N protein to co-localise genomic RNA with the nascent replicase-transcriptase complex at the earliest stages of infection, essential for the virus []. The C-terminal Glu-rich subdomain is best described as a flexible tail attached to the globular UB1 subdomain [].
Conjugative transposon protein TraQ, bacteroidetes
Type:
Family
Description:
This entry represents the conjugative transposon protein TraQ from Bacteroides thetaiotaomicron and similar sequences from Bacteroides species. TraQ shares structural similarity to other proteins involved in pili production for bacterial cell attachment [
]. The gene coding for this protein, located in a conjugate transposon, appears to be upregulated in the presence of host or other bacterial species compared to growth in pure culture [,
].
This entry represents a family of uncharacterised proteins found primarily in Bacteroides species. The Bacteroides thetaiotaomicron gene appears to be upregulated in the presence of host or other bacterial species compared to growth in pure culture [
,
].
Members of this family which have been characterised, belong to the small multidrug/metabolite transporter family and are integral membrane proteins. They confer resistance to a wide range of toxic compounds by removing them for the cells. The efflux is coupled to an influx of protons. It includes 4-amino-4-deoxy-L-arabinose-phosphoundecaprenol flippase subunit ArnE and ArnF, which are components of the undecaprenyl-phosphate-alpha-L-Ara4N flippase that translocates 4-amino-4-deoxy-L-arabinose-phosphoundecaprenol from the cytoplasmic to the periplasmic side of the inner membrane during lipopolysaccharide biosynthesis and is involved in polymyxin resistance [
]. Another example is Escherichia coli EmrE which confers resistance to a wide range of toxic compounds, including ethidium, methyl viologen [
,
], benzalkonium, propidium, dequalinium and different aromatic cation antibiotics and it is also involved in ethidium bromide efflux [,
]. It simultaneously binds and cotransports proton and drug [,
].
Gp28 is a structural component of the central part of the bacteriophage T4 baseplate. The membrane-bound protein forms a complex with an another baseplate structural component, Gp27 [
]. This complex may function as an initiator of the central hub assembly.
SAS4 is a fungal silencing regulator. In S. cerevisiae, Sas4 is a subunit of a histone acetyltransferase complex termed SAS complex, which consists of Sas2, Sas4 and Sas5 [
]. The SAS complex acetylates both free histones and nucleosomes and is involved in transcriptional silencing. Both Sas4 and Sas5 are required for optimal Sas2 histone acetyltransferase activity [].
Members of this family of actinobacterial proteins are described as putative PhiRv1/PhiRv2 prophage proteins, however their function is unknown. This two prophages have been detected in the genome sequence of Mycobacterium tuberculosis [
].
High potential iron-sulphur proteins (HiPIP) [
,
] are a specific class of high-redox potential 4Fe-4S ferredoxins that functions in anaerobic electron transport and which occurs commonly in purple photosynthetic bacteria and in other bacteria, such as Paracoccus denitrificans and Thiobacillus ferrooxidans [].HiPIPs seem to react by oxidation of [4Fe-4S]2+ to [4Fe-4S]3+The HiPIPs are small proteins which show significant variation in their sequences, their sizes (from 63 to 85 amino acids), and in their oxidation- reduction potentials. As shown in the following schematic representation the iron-sulphur cluster is bound by four conserved cysteine residues.[4Fe-4S cluster]
| | | |xxxxxxxxxxxxxxxxxxxCxCxxxxxxxCxxxxxCxxxx
'C': conserved cysteine involved in the binding of the iron-sulphur cluster.
These archaeal and bacterial proteins have no known function. Members of this family contain seven conserved cysteines and may also be an integral membrane protein [
].
This family includes a group of functionally uncharacterized hypothetical proteins from archaea and their bacterial homologs. These proteins contain a putative GIY-YIG domain that shows sequence homology with bacterial UvrC DNA repair proteins. Meanwhile, all of them share a C-terminal extension with semi-conserved Cys and His residues, which suggests that the extended region may be a zinc-binding nucleic acid interaction domain. Although the majority of family members have a standalone GIY-YIG domain composition, some of them do have additional endonulcease III domain or sugar fermentation stimulation protein domain, both of which are N-terminally fused to the GIY-YIG domain. As a result, those proteins could perform some other role by cooperating with different domains, which remains to be determined in the future [
].In Methanocaldococcus jannaschii (Methanococcus jannaschii) it occurs with an endonuclease domain
.
This entry includes uncharacterised archaebacterial proteins. Sequence and structure analysis to identify RNase H-like superfamily members, has clustered this family in endonuclease Clade V, thus suggesting endonuclease activity of these proteins [].
This entry represents a group of plant proteins, including protein modifier of SNC1 1 (MOS1) from Arabidopsis. MOS1 regulates the expression of suppressor of npr1-1, constitutive1 (SNC1), which encodes a Toll/interleukin receptor-nucleotide binding site-leucine-rich repeat type of resistance protein. It may function in regulation of gene expression at chromatin level [
].
Kelch-like protein 25 (KLHL25, also known as ENC-2) serves as a substrate-specific adapter in the Cul3-dependent ubiquitin ligase complex that targets hypophosphorylated 4E-BP1 (4E-binding protein 1) for degradation [
]. 4E-BPs regulate the activity of eIF4E, a mRNA 5' cap-binding protein and a major target for translational control [].The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding [
], while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins []. In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins []. Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases [,
].This entry represents the BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain found in KLHL25.
The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding [
], while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins [
]. In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins []. Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases [,
].Kelch-like protein 23 (KLHL23) belongs to the KLHL family [
]. KLHL23 overexpression is associated with increased cell proliferation and invasion in gastric cancer. Downregulation of KLHL23 is associated with invasion, metastasis, and poor prognosis of hepatocellular carcinoma and pancreatic cancer [,
,
]. This entry represents the BTB/POZ domain, a common protein-protein interaction motif of about 100 amino acids.
The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding [
], while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins []. In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins []. Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases [,
].Kelch-like protein 32 (KLHL32), also called BTB and kelch domain-containing protein 5 (BKLHD5) [
], contains a BTB domain and kelch repeats, characteristics of a kelch family protein. Its function remains unclear. Deletion of KLHL32 may be associated with Tourette syndrome and obsessive-compulsive disorder [,
]. Its function is not clear.This entry represents the BTB/POZ domain of KLHL32, a common protein-protein interaction module of about 100 amino acids.
The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding [
], while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins []. In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins []. Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases [,
].Kelch-like protein 41 (KLHL41), also known as sarcosin or Krp1, is involved in skeletal muscle development and differentiation [
,
]. KLHL41 binds to Nebulin, an actin-binding protein that regulates the actin filament length. It also binds Nebulin-related anchoring protein (N-RAP), an actin-binding protein expressed in skeletal and cardiac muscle tissues [,
]. KLHL41 is localised between laterally fusing myofibrils in adult skeletal muscle and plays an important role for the correct functioning of adult skeletal muscle cells [
]. Mutations in its gene lead to nemaline myopathy-9 (NEM9), a muscle disorder characterized by onset of muscle weakness in early infancy [].This group of proteins also includes the orthologue from fish Kelch-like protein 41b (KL41B), which is involved in skeletal muscle development and maintenance [
]. This entry represents the N-terminal BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain of mammal KLHL41, fish KL41B and related proteins from vertebrates.
The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding [
], while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins []. In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins []. Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases [,
].Kelch-like protein 21 (KLHL21) is a substrate adaptor protein in the Cul3-KLHL21 E3 ubiquitin ligase complex required for efficient chromosome alignment and cytokinesis. During cytokinesis, it localises to midzone microtubules in anaphase and recruits aurora B and Cul3 to this region [
]. KLHL21 also targets IkappaB kinase-beta to regulate nuclear factor kappa-light chain enhancer of activated B cells (NF-kappaB) signaling negatively [,
,
,
]. This entry represents the BTB/POZ domain.
The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding [
], while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins []. In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins []. Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases [,
].Kelch-like protein 14 (KLHL14) belongs to the KLHL family [
]. Its is also known as Printor (protein interactor of torsinA). It selectively binds to the ATP-free form, but not to the ATP-bound form of torsinA, suggesting a role for Printor as a cofactor rather than a substrate of the AAA+ protein torsinA and is implicated in dystonia pathogenesis [
,
,
].This entry represents the BTB/POZ domain of KLHL14, a common protein-protein interaction module of about 100 amino acids.
The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding [
], while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins []. In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins []. Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases [,
].Kelch-like protein 26 (KLHL26) is encoded by the klhl26 gene, which is regulated by p53 via fuzzy tandem repeats. It contains a BTB domain and kelch repeats, characteristics of a kelch family protein [
]. This entry represents the BTB/POZ domain, a common protein-protein interaction module of about 100 amino acids [].
The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding [
], while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins []. In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins []. Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases [,
].Kelch-like protein 24 (KLHL24, also known as kainate receptor-interacting protein for GluR6 (KRIP6) or protein DRE1) belongs to the KLHL family [
]. is necessary to maintain the balance between intermediate filament stability and degradation, a process that is essential for skin integrity. KLHL24 is a component of a BCR (BTB-CUL3-RBX1) E3 ubiquitin ligase complex that mediates ubiquitination of KRT14 and controls its levels during keratinocyte differentiation [,
,
,
,
. KLHL24 binds to and regulates the GluR6a kainate receptor [
]. It also modulates the interaction of PICK1 with GluR6 kainate receptors [,
,
]. Kainate receptors (KAR) are ionotropic receptors that respond to the neurotransmitter glutamate and have been implicated in epilepsy, stroke, Alzheimer's and neuropathic pain [].This entry represents the BTB/POZ domain.
The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding [
], while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins []. In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins []. Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases [,
].Kelch-like protein 15 (KLHL15) is a substrate-specific adaptor for the Cullin3 E3 ubiquitin-protein ligase complex that targets the serine/threonine-protein phosphatase 2A (PP2A) subunit PPP2R5B for ubiquitination and subsequent proteasomal degradation, thus promoting exchange with other regulatory subunits [
,
]. It also plays a key role in DNA damage response, favoring DNA double-strand repair through error-prone non-homologous end joining (NHEJ) over error-free, RBBP8-mediated homologous recombination (HR), by targeting the DNA-end resection factor RBBP8/CtIP for ubiquitination and subsequent proteasomal degradation. KLHL15 contains a BTB domain and kelch repeats, characteristics of a kelch family protein [,
,
].This entry represents the BTB/POZ domain of KLHL15, a common protein-protein interaction module of about 100 amino acids.
The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding [
], while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins []. In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins []. Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases [,
].Kelch-like protein 7 (KLHL7) belongs to the KLHL family [
]. It serves as a substrate-specific adapter in the Cul3-dependent ubiquitin ligase complex and is linked to autosomal dominant retinitis pigmentosa (adRP) []. This entry represents the BTB/POZ domain.
The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding [
], while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins []. In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins []. Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases [,
].Kelch-like protein 35 (KLHL35) belongs to the KLHL family [
]. Its function is not clear. Significant differences in the DNA methylation pattern of the KLHL35 gene have been associated with abdominal aortic aneurysm (AAA) and hepatocellular carcinoma [,
].This entry represents the N-terminal BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain of KLHL35 and similar proteins from vertebrates.
This entry represents the BTB/POZ domain found in Kelch-like protein 18 (KLHL18), which belongs to the KLHL family [
].The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding [
], while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins []. In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins []. Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases [,
].
The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding [
], while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins []. In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins []. Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases [,
].Kelch-like protein 31 (KLHL31) is also called BTB and kelch domain-containing protein 6 (BKLHD6), Kelch repeat and BTB domain-containing protein 1 (KBTBD1) []. It is a transcriptional repressor in the MAPK/JNK signaling pathway to regulate cellular functions []. Its overexpression inhibits the transcriptional activities of both the TPA-response element (TRE) and serum response element (SRE). It is linked to skeletal myogenesis and its expression is regulated by myogenic signals and Myf-5 [,
,
].This entry represents the BTB/POZ domain of KLHL31, a common protein-protein interaction module of about 100 amino acids.
This entry represents the BTB/POZ domain found in Kelch-like protein 5 (KLHL5), which belongs to the KLHL family [
]. The function of KLHL5 is not clear [].The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding [
], while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins []. In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins []. Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases [,
].
Kelch-like protein 40 (KLHL40, also known as Kbtbd5) belongs to the KLHL family [
]. Mutations in the KLHL40 gene cause severe autosomal-recessive nemaline myopathy, which is a congenital myopathy that can result in lethal muscle dysfunction [,
]. Kbtbd5 may serve as an adapter in the Cul3-dependent ubiquitin ligase complex during myogenic differentiation [].The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding [
], while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins []. In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins []. Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases [,
].This entry represents the BTB (Broad-Complex, Tramtrack and Bric a brac)/POZ (poxvirus and zinc finger) domain of KLHL40.
Kelch-like protein 10 (KLHL10) belongs to the KLHL family [
]. It may serve as an adapter in the Cul3-dependent ubiquitin ligase complex during spermatogenesis. It is required for male fertility in mice [,
].The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding [
], while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins []. In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins []. Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases [,
].
The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding [
], while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins []. In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins []. Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases [,
].Kelch-like protein 6 (KLHL6) is involved in B-lymphocyte antigen receptor signalling and germinal centre formation [
]. Mutations in KLHL6 gene have been linked to chronic lymphocytic leukaemia (CLL) []. This entry represents the BTB/POZ domain.
The KLHL (Kelch-like) proteins generally have a BTB/POZ domain, a BACK domain, and five to six Kelch motifs. They constitute a subgroup at the intersection between the BTB/POZ domain and Kelch domain superfamilies. The BTB/POZ domain facilitates protein binding [
], while the Kelch domain (repeats) form β-propellers. The Kelch superfamily of proteins can be subdivided into five groups: (1) N-propeller, C-dimer proteins, (2) N-propeller proteins, (3) propeller proteins, (4) N-dimer, C-propeller proteins, and (5) C-propeller proteins. KLHL family members belong to the N-dimer, C-propeller subclass of Kelch repeat proteins []. In addition to BTB/POZ and Kelch domains, the KLHL family members contain a BACK domain, first described as a 130-residue region of conservation observed amongst BTB-Kelch proteins []. Many of the Kelch-like proteins have been identified as adaptors for the recruitment of substrates to Cul3-based E3 ubiquitin ligases [,
].IPP (also known as Kelch-like protein 27) belongs to the KLHL family. It binds to actin through its kelch repeat domain [
]. It may play a role in organizing the actin cytoskeleton, however, its exact function is not clear. This entry represents the BTB/POZ domain.
This entry consists of the suppressor APC domain-containing protein 1 and 2 (SAPCD1 and SAPCD2). SAPCD2 is expressed in many primary gastric carcinoma. It is expressed preferentially in M and G1 phases, compared to S and G2 phases [
].
This entry represents the structural accessory protein ORF7a from SARS-CoV-like virus, including SARS-CoV, SARS-CoV-2 and bat SARS-like coronavirus.
This entry includes the structural accessory protein ORF7a, also called NS7a, X4 and U122, of Severe Acute Respiratory Syndrome Coronaviruses (SARS-CoV) from betacoronavirus subgenera Sarbecovirus (lineage B), including SARS-CoV-2. ORF7a/NS7a from betacoronavirus in the subgenera Sarbecovirus (B lineage) are not related to NS7a proteins from other coronavirus lineages. The structure of the structural accessory protein ORF7a, shows similarities to the immunoglobulin-like fold with some features resembling those of the Dl domain of ICAM-1 and suggests a binding activity to integrin I domains [
]. In SARS-CoV-infected cells, ORF7a is expressed and retained intracellularly within the Golgi network []. ORF7a is thought to play an important role during the SARS-CoV replication cycle []. Expression studies of ORF7a have shown that biological functions include induction of apoptosis through a caspase-dependent pathway, activation of the p38 mitogen-activated protein kinase signaling pathway, inhibition of host protein translation, and suppression of cell growth progression. These results collectively suggested that ORF7a protein may be involved in virus-host interactions [
]. Studies in SARS-CoV-2 revealed that ORF7a plays a role as antagonist of host tetherin (BST2), disrupting its antiviral effect. ORF7a binds to BST2 and sequesters it to the perinuclear region, thereby preventing its antiviral function at cell membrane [].
Structural accessory protein ORF7a, SARS-CoV-2-like
Type:
Family
Description:
SARS-CoV contains a number of open reading frames that code for a total of eight accessory proteins, namely ORFs 3a, 3b, 6, 7a, 7b, 8a, 8b, and 9b. These ORFs are specific for SARS-CoV and do not show significant homology to accessory proteins of other coronaviruses. This entry represents the structural accessory protein ORF7a, also called NS7a, of Severe Acute Respiratory Syndrome Coronaviruses (SARS-CoV) from betacoronavirus subgenera Sarbecovirus (lineage B), including SARS-CoV-2. ORF7a/NS7a from betacoronavirus in the subgenera Sarbecovirus (B lineage) are not related to NS7a proteins from other coronavirus lineages.
Structurally, ORF7a possesses a distinctive immunoglobulin (Ig)-like domain which is related to extracellular metazoan Ig domains that are involved in adhesion, such as ICAM; it also contains a 15-aa signal peptide sequence at its N terminus, an 81-aa luminal domain, a 21-aa transmembrane domain, and a short C-terminal tail. Coexpression of SARS-CoV ORF7a with S, M, N, and E proteins resulted in production of virus-like particles (VLPs) carrying ORF7a protein, indicating that ORF7a is a viral structural protein. Expression studies of ORF7a have shown that biological functions include induction of apoptosis through a caspase-dependent pathway, activation of the p38 mitogen-activated protein kinase signaling pathway, inhibition of host protein translation, and suppression of cell growth progression. These results collectively suggested that ORF7a protein may be involved in virus-host interactions []. Studies in SARS-CoV-2 revealed that ORF7a plays a role as antagonist of host tetherin (BST2), disrupting its antiviral effect. ORF7a binds to BST2 and sequesters it to the perinuclear region, thereby preventing its antiviral function at cell membrane [].
This family of proteins is functionally uncharacterised. Proteins in this family are approximately 140 amino acids in length and share two CXXC motifs suggesting these are zinc binding proteins. In clostridia proteins are found in an operon with three signalling proteins, suggesting that they are involved in DNA-binding transcription regulator downstream of an as yet unknown signalling pathway.
This is a family of uncharacterised bacterial proteins. However, structural-similarity searches indicate the family takes on an actin-like ATPase fold.
This entry represents a family of functionally uncharacterised proteins that are found in bacteria. Proteins in this family are approximately 190 amino acids in length.
This entry represents a family of proteins mainly found in Bacillus, including Uncharacterized protein YizC from Bacillus subtilis (strain 168). YizC might be involved in sporulation [
].
The small integral membrane protein 9 (Smim9) is an uncharacterized, membrane protein. It has a signal peptide, a small extracellular domain, a single transmembrane region, and a short cytoplasmic tail. It is known from mammals and birds.
This family of proteins is functionally uncharacterised. Proteins in this family are approximately 60 amino acids in length and contain a conserved TAAW sequence motif that may be functionally important.
Cilia- and flagella-associated protein 157 (CFAP157) has been characterized as a component on the flagellum from the green alga Chlamydomonas reinhardtii by mass spectroscopy [
]. Related proteins are found in animals. In mouse, CFAP157 is required for sperm motility and flagellum morphogenesis [].
Members of this family include the Bacillus subtilis spore coat protein H (CotH). Assembly of CotH requires both CotE and GerE and is required for the correct assembly of both inner and outer layers of the coat. CotH appears to be a structural component of the coat being localised at the interface of the 2 coat layers [
,
,
]. Furthermore, CotH has been shown to be an atypical protein kinase. CotH-dependent phosphorylation of CotB and CotG is required for the efficient germination of B. subtilis spores [].This entry also includes CotH2/3/7 from Rhizopus delemar (mucormycosis agent), which promote invasion of host epithelial cells by adhering to receptors on the host cell surface to facilitate endocytosis of the pathogen into host cells [
,
].
This entry includes cell division cycle-associated protein 3 (CDCA3; also known as trigger of mitotic entry protein 1 or TOME-1), which is required for entry into mitosis. The protein is found at high levels during the G2 and M phases of mitosis, but declines rapidly during the G2 phase. Entry into mitosis requires the relocalization to the nucleus and activation of cyclin-dependent kinase 1 (cdk1) by association with cyclin B, and exit from mitosis occurs when cyclin B is degraded and the kinase activity decreases. Anaphase promoting complex (APC) is an E3 ligase active during anaphase and G1, and is required for the degradation of cyclin B. CDCA3 is a cytosolic protein and a substrate of APC. It associates with Skp-1 and is required for the degradation of the cdk1 inhibitor wee1, a tyrosine kinase. Degradation of CDCA3 leads to an accumulation of wee1 during interphase [
]. The CDCA3 protein contains an F-box-like region and a KEN box; the latter is required for association with the APC complex.
This entry represents a group of plant proteins, including shortage in chiasmata 1 (SHOC1) from Arabidopsis. SHOC1 is essential for the formation of class I meiotic crossovers [
,
].
This entry represents functionally uncharacterised proteins that are found in bacteria. They are typically between 247 and 417 amino acids in length. Most of the proteins in this entry have an N-terminal lipoprotein attachment site. These proteins have distant similarity to periplasmic ligand binding families suggesting that this family has a similar role.
This family of proteins is functionally uncharacterised. This family of proteins is found in bacteria. Proteins in this family are approximately 120 amino acids in length.
CFAP61/FAP61 is part of the calmodulin and spoke-associated complex (CSC) required for wild-type motility and for the stable assembly of a subset of radial spokes in motile cilia [
].
