https://www.genecards.org/cgi-bin/carddisp.pl?gene=SART3&keywords=SART3
måndag 10 november 2025
måndag 27 oktober 2025
SLC30A sinkinkuljettajat ZNT siirtävät sikkiä pois sytoplamasta ulos solusta ja erilaisiin erilaisiin organelleihin ja sinkkihomeostaasissa.
https://www.researchgate.net/publication/322712966_SLC30A_family_expression_in_the_pancreatic_islets_of_humans_and_mice_cellular_localization_in_the_b-cells ZNT perhettä on 10 ja niillä alaperheet I-IV. Tämän fylogeneettinen puu voidaan piirtää toisiaan kuin puuna, jonka lehdet tippuvat, jota ymmärretään, että suunta on poispäin tavalla tai toisella. Puun lehdestäkin teitysti luonnossa imeytyy ravinteita takaisinpäin, muta sinkillä on se homeostaasi se järki tässä ideassa. Homeostaasi näiden kahden voiman välillä. https://www.researchgate.net/figure/of-the-ZNT-family-a-phylogenetic-tree-of-the-ZNT-family-members-Amino-acid-sequences-of_fig1_322712966
Nämä ulos sytoplasman alueesta sinkkiä siirtävät ZNT(SLC39A) kuljettajat suorittavat päinvastaista toimintaa kuin ZIP (SLC39A)
ZIP (SLC39A) sinkinkuljettajaperheen alaperheet ovat neljä I, II, LIV-1 ja gufA. Vastaavat sinkinpuutteeseen ja asettavat sinkkiä tarvittaviin kohtiin sinkkitasapainossa.
SLC39A sinkinkuljettajaproteiinien ZIP alaperheet
Subfamily, Alaperhe I:
ZIP9
Alaperhe II:
ZIP1, ZIP2, ZIP3.
Alaperhe LIV-1:
ZIP4, ZIP5, ZIP6, ZIP7, ZIP8, ZIP10, ZIP13, ZIP14._
Alaperhe GufA:
ZIP11.
https://pmc.ncbi.nlm.nih.gov/articles/PMC3602797/
- Alla olevasta artikkelista löytyy ZIP (SKC39A perheen fylogeneetinen puu alaperheineen.FIGURE1.
Lintuinfluenssa nostaa päätään Ruotsissa, kertoo Aftonbladet tänään erityisen mainnan 27.10.2025
Jordbruksverket har även beslutat om högriskområden i södra Sverige från och med 27 oktober för att skydda svenska fågelbesättningar.
Det innebär att alla fjäderfän inom högriskområdet ska hållas inomhus.
Enligt myndigheten är det en ovanligt hög smittspridning av fågelinfluensa i vår omvärld nu i år.
Djurägare uppmanas därför att direkt ta kontakt med en veterinär om deras fjäderfän plötsligt dör eller blir sjuka.
DENGUE j reseptori , yksi monista: (Tigh junction- komponentti) Claudin1) CLDN1-CD81 (tetraspanin)
UniProtKB/Swiss-Prot Summary for CLDN1 Gene
Claudins function as major constituents of the tight junction complexes that regulate the permeability of epithelia. While some claudin family members play essential roles in the formation of impermeable barriers, others mediate the permeability to ions and small molecules. Often, several claudin family members are coexpressed and interact with each other, and this determines the overall permeability. CLDN1 is required to prevent the paracellular diffusion of small molecules through tight junctions in the epidermis and is required for the normal barrier function of the skin. Required for normal water homeostasis and to prevent excessive water loss through the skin, probably via an indirect effect on the expression levels of other proteins, since CLDN1 itself seems to be dispensable for water barrier formation in keratinocyte tight junctions (PubMed:23407391). ( CLD1_HUMAN,O95832 )
(Microbial infection) Acts as a co-receptor for hepatitis C virus (HCV) in hepatocytes (PubMed:17325668, 20375010, 24038151). Associates with CD81 and the CLDN1-CD81 receptor complex is essential for HCV entry into host cell (PubMed:20375010).
Acts as a receptor for dengue virus (PubMed:24074594). ( CLD1_HUMAN,O95832 ) Dengue disease is becoming a huge public health concern around the world as more than one-third of the world's population living in areas at risk of infection. In an effort to assess host factors interacting with dengue virus, we identified claudin-1, a major tight junction component, as an essential cell surface protein for dengue virus entry. When claudin-1 was knocked down in Huh 7.5 cells via shRNA, the amount of dengue virus entering host cells was reduced. Consequently, the progeny virus productions were decreased and dengue virus-induced CPE was prevented. Furthermore, restoring the expression of claudin-1 in the knockdown cells facilitated dengue virus entry. The interaction between claudin-1 and dengue viral prM protein was further demonstrated using the pull-down assay. Deletion of the extracellular loop 1 (ECL1) of claudin-1 abolished such interaction, so did point mutations C54A, C64A and I32M on ECL1. These results suggest that the interaction between viral protein prM and host protein claudin-1 was essential for dengue entry. Since host and viral factors involved in virus entry are promising therapeutic targets, determining the essential role of claudin-1 could lead to the discovery of entry inhibitors with attractive therapeutic potential against dengue disease.
- AI mainitsee että Dengue käyttää useita reseptoreita. Katson jonki artikkelin.
https://link.springer.com/article/10.1007/s40475-013-0002-7
Glycosaminoglycans (GAGs) and other attachment factors
The first molecule that was identified to participate in DENV entry into mammalian cells was heparan sulfate [20–22]. Highly sulfated GAGs are ubiquitous molecules present on the surface of several types of cells, also mediating attachment for many viruses [23]. It is documented that there are electrostatic attractions among a dengue virus E glycoprotein and the negatively charged carbohydrate moieties present in GAGs [24]. Due to the documented evidence that the GAGs-DENV interactions are stronger when the virus has been passaged in cell-culture repetitively, and due to its correlation with in vivo attenuation, it has been suggested its role is artifactual.
The most relevant attachment factor for DENV entry identified so far is the calcium-dependent lectin, dendritic cell-specific intercellular adhesion molecule 3-grabbing non-integrin (DC-SIGN) [25–27]. This receptor has high affinity for high-mannose ligands [28]. During the mosquito blood-meal, DENV is deposited in the dermis where its interaction with resident dendritic cells (Langerhans cells) has been documented [6]. Upon entry, dendritic cells migrate to draining lymph nodes where the infection is spread to immune-competent myelo-monocytic cells. Whether DC-SIGN is the only factor responsible for dengue virus entry or the virus replicates actively in dendritic cells is still unknown.
Another lectin that may play a role in dengue virus attachment is the C-type lectin domain family-5 member A (CLEC5) [29, 30]. This molecule has been documented to participate in viral attachment and release of pro-inflammatory mediators important in the pathogenesis of severe forms of dengue [31, 32]. In sum, it is clear that the first step in dengue virus entry involves attachment of the virion to the cell surface.
Cell surface chaperones
Among DENV entry factors identified thus far, there is a group that has been described by independent groups, the surface chaperones. Experimentally, these molecules have been found through binding assays using the envelope glycoprotein as a ligand. HSP-90, HSP-70 and GRP-78 are thought to be part of a receptor complex that mediates dengue entry into human cells from monocytic, neural and hepatic origin [33, 34]. It is not known whether their extracellular function is similar to their well-known intracellular, ATP-dependent protein folding activity, or how they associate with the cell membrane. It has been long been reported that lipopolysaccharide (LPS) inhibits DENV entry into monocytes [35]. This effect is dose dependent. On this regard, surface HSPs were also documented as part of an interacting cluster of plasmatic proteins mediating physiological effects of LPS sensing on cells [36]. It is tempting to propose that heat shock as an effect on DENV entry through the increase of heat-shock-responsive molecules on the surface of infected cells. This effect was documented in the infection of a monocytic cell line [37]. Another protein with chaperone function reported as a DENV receptor is the protein disulfide isomerase (PDI). This has been implicated in DENV entry into endothelial cells [38•]. Besides its important role in the endoplasmic reticulum, it has been detected on the cell surface of lymphocytes [39], platelets [40, 41], and endothelial cells [38•]. PDI has been implicated in entry of several viruses such as polyomavirus [42], New Castle disease virus [43], and the human immunodeficiency virus [39, 44, 45].
Lipid receptors
(PtdSer)rec TIM1-TAM ligands
The only gain-of-function screening in the search for DENV receptors found that phosphatydilserine (PtdSer) receptors TIM-1 (T cell immunoglobulin domain and mucin domain) directly and indirectly through TAM ligands, are relevant on DENV entry into the human 293 T cell line [46•]. These receptors mediate binding of apoptotic cells to be scavenged and immunotolerance. Therefore, an intimate interaction of cell receptors with lipids present on the virion membrane envelope suggests the structure of entering particles needs to be revisited. In any case, the lipid content present on the target cell has long been demonstrated as important to optimize DENV entry.
torsdag 23 oktober 2025
DENGUE2 infektion, P. falciparum malarian ja Borrelian invaasiota ja disseminaatiota lisää plasminogeenin pilkkoutumistuote plasmiini
https://www.uniprot.org/uniprotkb/P00747/entry#function
Olen katsomassa plasminogeenin pilkkoutuistuotteita plasmiini ja angiostatiini. Sivumennen huomaan maininnan dengue2 virustulehduksesta .
Function
function
Plasmin
dissolves the fibrin of blood clots and acts as a proteolytic factor in
a variety of other processes including embryonic development, tissue
remodeling, tumor invasion, and inflammation. In ovulation, weakens the
walls of the Graafian follicle. It activates the urokinase-type
plasminogen activator, collagenases and several complement zymogens,
such as C1, C4 and C5 (PubMed:6447255).
Cleavage of fibronectin and laminin leads to cell detachment and apoptosis. Also cleaves fibrin, thrombospondin and von Willebrand factor. Its role in tissue remodeling and tumor invasion may be modulated by CSPG4. Binds to cells
Cleavage of fibronectin and laminin leads to cell detachment and apoptosis. Also cleaves fibrin, thrombospondin and von Willebrand factor. Its role in tissue remodeling and tumor invasion may be modulated by CSPG4. Binds to cells
Angiostatin
is an angiogenesis inhibitor that blocks neovascularization and growth
of experimental primary and metastatic tumors in vivo.
(Microbial
infection) ENO/enoloase from parasite P.falciparum (strain NF54)
interacts with PLG present in the mosquito blood meal to promote the
invasion of the mosquito midgut by the parasite ookinete (PubMed:21949403).
The catalytic active form, plasmin, is essential for the invasion of the mosquito midgut (PubMed:21949403).
The catalytic active form, plasmin, is essential for the invasion of the mosquito midgut (PubMed:21949403).
(Microbial
infection) Binds to OspC on the surface of B.burgdorferi cells,
possibly conferring an extracellular protease activity on the bacteria
that allows it to traverse host tissue.
(Microbial infection) Interacts with dengue virus type 2 particles (PubMed:31726374).
Enhances dengue virus type 2 infection in Aedes aegypti mosquito midgut by increasing midgut internalization, resulting in higher infection rates and viral dissemination in mosquitoes (PubMed:31726374).
Enhances dengue virus type 2 infection in Aedes aegypti mosquito midgut by increasing midgut internalization, resulting in higher infection rates and viral dissemination in mosquitoes (PubMed:31726374).
Miscellaneous
Plasmin is inactivated by alpha-2-antiplasmin immediately after dissociation from the clot.
Catalytic activity
Preferential cleavage: Lys-|-Xaa > Arg-|-Xaa, higher selectivity than trypsin. Converts fibrin into soluble products.
)
Activity regulation
Converted
into plasmin by plasminogen activators, both plasminogen and its
activator being bound to fibrin. Activated with catalytic amounts of
streptokinase. Plasmin activity inhibited by SERPINE2.
Features
Showing features for site, binding site, active site.
måndag 13 oktober 2025
Rokotteen POXvirus VACV ilmentää immunomodulatorisia proteiineja kuten BTB-BACK-Kelch-kaltaisia(BBK) proteiineja. Muita POX viruksia ja niiden koodaamia proteiineja
1.2 LSDV cluster
28 results
Genomic Analysis of Lumpy Skin Disease Virus from
Western and Central Africa Suggests a Distinct Sub-Lineage Within the
1.2 LSDV Cluster.
Pathogens. 2025 Sep 12;14(9):922. doi: 10.3390/pathogens14090922.
PMID: 41011822
Free PMC article.
Phylogenetic evaluation revealed that LSDV strains from Nigeria and
Cameroon cluster within the classical 1.2 lineage. Furthermore, the two
sequences from this study cluster with the only publicly available
sequence from West and Central Africa, supporting earlier findings of
the presence of a West/Central African sub-lineage. Functional genomic
analysis identified mutations in genes encoding ankyrin repeat
Kelch-like proteins, and envelope proteins involved in immune evasion
and viral virulence, raising concerns about vaccine effectiveness.
Furthermore, the detection of LSDV in flesh flies (Sarcophaga
spp.) underlines their potential role in virus transmission. These
findings highlight the importance of genomic monitoring and targeted
surveillance.toistoisia KELCH-proteiinien kaltaisia
Genetic Evolutionary Analysis of Lumpy Skin Disease
Virus Strain Under Immune Pressure Exerted by Heterologous Goat Poxvirus Vaccines.
Transbound Emerg Dis. 2025 Feb 23;2025:2883245. doi: 10.1155/tbed/2883245. eCollection 2025.
PMID: 40302761
Free PMC article.
Recently, LSD has occurred frequently in Asia. The attenuated goat poxvirus
(GTPV) vaccine is widely used to prevent LSD in cattle in China;
however, sporadic cases of LSD still occur in immunized cattle. ...There
are several open reading frames (ORFs) differences between …
Genomic characterization of Lumpy Skin Disease virus
(LSDV) from India: Circulation of Kenyan-like LSDV strains with unique kelch-like proteins.
Acta Trop. 2023 May;241:106838. doi: 10.1016/j.actatropica.2023.106838. Epub 2023 Feb 15.
PMID: 36796571
Phylogenetic analysis based on complete genome sequence
suggested that LSDV-WB/IND/19 is closely related to Kenyan LSDV strains
with 10-12 variants with non-synonymous changes confined to LSD_019,
LSD_049, LSD_089, LSD_094, LSD_096, LSD_140, and LSD_144 genes. In
contrast to comp …
Emergence of a new lumpy skin disease virus variant in Kurgan Oblast, Russia, in 2018.
Arch Virol. 2020 Jun;165(6):1343-1356. doi: 10.1007/s00705-020-04607-5. Epub 2020 Apr 11.
PMID: 32279139
Due to these incongruent phylogenetic patterns, the sequences of three additional loci ORF19 (Kelch-like protein), ORF52 (putative transcriptional elongation factor), and ORF87 (mutT motif protein) were investigated. ...
Kelch-like proteins: Physiological functions and relationships with diseases.
Pharmacol Res. 2019 Oct;148:104404. doi: 10.1016/j.phrs.2019.104404. Epub 2019 Aug 20.
PMID: 31442578
Review.
Kelch-like gene family members (KLHLs) encode proteins with a bric-a-brac, tramtrack, broad complex (BTB)/poxvirus
and zinc finger (POZ) domain, a BACK domain, and six Kelch motifs,
which frequently interact with Cullin3 to form E3 ligase complexes tha …
Extended sequencing of vaccine and wild-type
capripoxvirus isolates provides insights into genes modulating virulence
and host range.
Transbound Emerg Dis. 2020 Jan;67(1):80-97. doi: 10.1111/tbed.13322. Epub 2019 Aug 30.
PMID: 31379093
The genus Capripoxvirus in the subfamily Chordopoxvirinae, family Poxviridae,
comprises sheeppox virus (SPPV), goatpox virus (GTPV) and lumpy skin
disease virus (LSDV), which cause the eponymous diseases across parts of
Africa, the Middle East and Asia. ...In particular, s …
Vaccinia Virus BBK E3 Ligase Adaptor A55 Targets Importin-Dependent NF-κB Activation and Inhibits CD8+ T-Cell Memory.
J Virol. 2019 May 1;93(10):e00051-19. doi: 10.1128/JVI.00051-19. Print 2019 May 15.
PMID: 30814284
Free PMC article.
Viral infection of cells is sensed by pathogen recognition receptors that trigger an antiviral innate immune response, and consequently viruses have evolved countermeasures. Vaccinia virus (VACV) evades the host immune response by expressing scores of immunomodulatory proteins. One family of VACV proteins are the BTB-BACK (broad-complex, tram-trac, and bric-a-brac [BTB] and C-terminal Kelch [BACK]) domain-containing, Kelch-like (BBK) family of predicted cullin-3 E3 ligase adaptors: A55, C2, and F3. Previous studies demonstrated that gene A55R encodes a protein that is nonessential for VACV replication yet affects viral virulence in vivo Here, we report that A55 is an NF-κB inhibitor acting downstream of IκBα degradation, preventing gene transcription and cytokine secretion in response to cytokine stimulation. A55 targets the host importin α1 (KPNA2), acting to reduce p65 binding and its nuclear translocation. Interestingly, while A55 was confirmed to coprecipitate with cullin-3 in a BTB-dependent manner, its NF-κB inhibitory activity mapped to the Kelch domain, which alone is sufficient to coprecipitate with KPNA2 and inhibit NF-κB signaling. Intradermal infection of mice with a virus lacking A55R (vΔA55) increased VACV-specific CD8+ T-cell proliferation, activation, and cytotoxicity in comparison to levels of the wild-type (WT) virus. Furthermore, immunization with vΔA55 induced increased protection to intranasal VACV challenge compared to the level with control viruses. In summary, this report describes the first target of a poxvirus-encoded BBK protein and a novel mechanism for DNA virus immune evasion, resulting in increased CD8+ T-cell memory and a more immunogenic vaccine.
IMPORTANCE NF-κB is a critical transcription factor in the innate immune response to infection and in shaping adaptive immunity. The identification of host and virus proteins that modulate the induction of immunological memory is important for improving virus-based vaccine design and efficacy. In viruses, the expression of BTB-BACK Kelch-like (BBK) proteins is restricted to poxviruses and conserved within them, indicating the importance of these proteins for these medically important viruses. Using vaccinia virus (VACV), the smallpox vaccine, we report that the VACV BBK protein A55 dysregulates NF-κB signaling by disrupting the p65-importin interaction, thus preventing NF-κB translocation and blocking NF-κB-dependent gene transcription. Infection with VACV lacking A55 induces increased VACV-specific CD8+ T-cell memory and better protection against VACV challenge. Studying viral immunomodulators therefore expands not only our understanding of viral pathogenesis and immune evasion strategies but also of the immune signaling cascades controlling antiviral immunity and the development of immune memory.
Keywords: BTB-Kelch; E3 ligase; NF-κB; cullin-3; importins; protein A55; vaccinia virus.
…
VARV B22R homologue as phylogenetic marker gene for Capripoxvirus classification and divergence time dating.
Virus Genes. 2019 Feb;55(1):51-59. doi: 10.1007/s11262-018-1613-9. Epub 2018 Nov 16.
PMID: 30446925
…Sheeppox disease is associated with significant losses in sheep
production world over. The sheep pox virus, the goatpox virus, and the
lumpy skin disease virus cannot be distinguished by conventional
serological tests. Identification of these pathogens needs molecular
methods. In this study, seven genes viz. EEV maturation protein-F12L,
Virion protein-D3R, RNA polymerase subunit-A5R, Virion core
protein-A10L, EEV glycoprotein-A33R, VARV B22R homologue, and Kelch like
protein-A55R that cover the start, middle, and end of the genome were
selected. These genes were amplified from Roumanian-Fanar vaccine strain
and Jaipur virulent strain, cloned, and sequenced. On analysis with the
available database sequences, VARV B22R homologue was identified as a
marker for phylogenetic reconstruction for classifying the sheeppox
viruses of the ungulates. Further, divergence time dating with VARV B22R
gene accurately predicted the sheeppox disease outbreak involving
Jaipur virulent strain.
Isolation and genetic characterization of swinepox virus from pigs in India.
Comp Immunol Microbiol Infect Dis. 2016 Jun;46:60-5. doi: 10.1016/j.cimid.2016.04.001. Epub 2016 Apr 4.
PMID: 27260812 Keywords:
Ankyrin- repeat protein; Extracellular enveloped protein; Host-range genes; Kelch-like protein; Swinepox virus.
Klhl31 attenuates β-catenin dependent Wnt signaling and regulates embryo myogenesis.
Dev Biol. 2015 Jun 1;402(1):61-71. doi: 10.1016/j.ydbio.2015.02.024. Epub 2015 Mar 19.
PMID: 25796573
Free article.
Klhl31 is a member of the Kelch-like family in vertebrates, which are characterized by an amino-terminal broad complex tram-track, bric-a-brac/poxvirus and zinc finger (BTB/POZ) domain, carboxy-terminal Kelch repeats and a central linker region (Back domain). … Klhl31 interferes with β-catenin dependent Wnt signaling. Klhl31
reduced the Wnt-mediated activation of a luciferase reporter in cultured
cells. Furthermore, Klhl31 attenuated secondary axis formation in
Xenopus embryos in response to Wnt1 or β-catenin. Klhl31 mis-expression
in the developing neural tube affected its dorso-ventral patterning and
led to reduced dermomyotome and myotome size. Co-transfection of a Wnt3a
expression vector with Klhl31 in somites or in the neural tube rescued
the phenotype and restored the size of dermomyotome and myotome. Thus,
Klhl31 is a novel modulator of canonical Wnt signaling, important for
vertebrate myogenesis. We propose that Klhl31 acts in the myotome to
support cell cycle withdrawal and differentiation.
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