atypical

ACKR1 Protein, Human, Recombinant (His) is expressed in E. coli expression system with N-10xHis tag. The predicted molecular weight is 41.1 kDa and the accession number is Q16570.

Interferon-gamma receptor beta chain (IFNgammaR2), also known as IFNGR2, belongs to the type II cytokine receptor family, whose deficiency is a cause of autosomal recessive mendelian susceptibility to mycobacterial disease (MSMD), also known as familial disseminated atypical mycobacterial infection. This accessory factor is an integral part of the IFN-gamma signal transduction pathway and is likely to interact with GAF, JAK1, and/or JAK2. IFNGR2 is a component of the IFNgamma receptor complex along with the IFNgammaR alpha chain (IFNGR1) and is a new Bax suppressor. The C-terminal fragment (cytoplasmic domain) of IFNgammaR2 is expressed in human cancer cell lines of megakaryocytic cancer (DAMI), breast cancer (MDA-MD-468), and prostate cancer (PC3 cells). The Th1 cytokine IFNgamma, acting through its heterodimeric receptors, IFNgammaR1 and IFNgammaR2, in the induction/proliferation of Th1 cells, might suppress the Th2 responses that may underlie atopic asthma. IFNGR2 has always been seen as a key mechanism for shielding T lymphocytes from the antiproliferative effects of the IFNgamma-signal transducer and activator of the transcription 1 (STAT1) pathway.

NKp80, also known as KLRF1, is an activating homodimeric C-type lectin-like receptor that is expressed on nearly all-natural killer cells and stimulates their cytotoxicity and cytokine release. NKp80 stimulates cytotoxicity upon engagement of its genetically linked ligand: myeloid-specific CTLR activation-induced C-type lectin (AICL). NKp80, but not NKp80 mutated at tyrosine 7 (NKp80/Y7F), is tyrosine phosphorylated. Accordingly, NKp80/Y7F, but not NKp80/Y3F or NKp80/Y37F, failed to induce cytotoxicity. NKp80 phosphopeptides comprising the Hemi-ITAM-like sequence surrounding tyrosine 7 bound Lck- and Syk-family kinases; accordingly, cross-linking of NKp8, but not NKp80/Y7F, induced Syk phosphorylation. Moreover, inhibition of Syk kinase, but not ZAP-7 kinase, impaired cytotoxic responses through NKp80. Atypical residues in the Hemi-ITAM-like motif of NKp80 cause an altered stoichiometry of phosphorylation but did not substantially affect NK cytotoxicity. Altogether, these results show that NKp80 uses an atypical Hemi-ITAM and Syk kinase to trigger cellular cytotoxicity.

Cell division protein kinase 5, also known as Cyclin-dependent kinase 5, Serine/threonine-protein kinase PSSALRE, Tau protein kinase II catalytic subunit, TPKII catalytic subunit and CDK5, is a cytoplasm protein which belongs to theprotein kinase superfamily, CMGC Ser/Thr protein kinase family and CDC2 / CDKX subfamily. Cyclin-dependent kinases (Cdks) are a family of proline-directed Ser/Thr kinases known for their role in the control of cell cycle progression. In 1992, this family was joined by CDK5, which is an atypical member in that it uses its own activators and is multifunctional, playing important regulatory roles in multiple cellular functions. CDK5, unlike other Cdks, is not regulated by cyclins, and its activity is primarily detected in postmitotic neurons in developing and adult nervous systems. CDK5 is activated by association with a neuron-specific activator, p35 or its isoform p39. CDK5 is probably involved in the control of the cell cycle. It interacts with D1 and D3-type G1 cyclins. CDK5 can phosphorylate histone H1, tau, MAP2 and NF-H and NF-M. It also interacts with p35 which activates the kinase. CDK5 plays important roles in various neuronal activities, including neuronal migration, synaptic activity, and neuronal cell death.

Apolipoprotein-D (ApoD) is an atypical apolipoprotein and, based on its primary structure, it also a member of the lipocalin family. ApoD is mainly associated with high density lipoproteins in human plasma. ApoD is expressed in numerous tissues having high levels of expression in spleen, testes and brain. ApoD plays a role in maintenance and repair within the central and peripheral nervous systems. ApoD occurs in the macromolecular complex with lecithin-cholesterol acyltransferase. It is a multi-ligand, multi-functional transporter and transports a ligand from 1 cell to another. ApoD is probably involved in the transport and binding of bilin, it appears to be able to transport a variety of ligands in a number of different contexts.

Factor H is the major soluble inhibitor of complement, where its binding to self markers (i.e., particular glycan structures) prevents complement activation and amplification on host surfaces. Not surprisingly, mutations and polymorphisms that affect recognition of self by factor H are associated with diseases of complement dysregulation, such as age-related macular degeneration and atypical haemolytic uremic syndrome. In addition, pathogens (i.e., non-self) and cancer cells (i.e., altered-self) can hijack factor H to evade the immune response.

Peroxisomes are essential organelles that participate in multiple important metabolic processes, including the β-oxidation of fatty acids, plasmalogen synthesis, and the metabolism of reactive oxygen species (ROS). Peroxiredoxins is overexpressed in breast cancer tissues to a great extent suggesting that they has a proliferative effect and may be related to cancer development or progression. Peroxiredoxin 5 (PRDX5) is a thioredoxin peroxidase that belongs to the atypical 2-Cys class of the TSA/ahpC family of peroxiredoxins. PRDX5 is a widely expressed mitochondrial antioxidant enzyme that reduces hydrogen peroxide, alkyl hydroperoxides, and peroxynitrite. In human cells, this enzyme is present in the cytosol, mitochondria, peroxisomes, and nucleus.

Classic Cadherins represent a family of calcium-dependent homophilic cell-cell adhesion molecules. They confer strong adhesiveness to animal cells when they are anchored to the actin cytoskeleton via their cytoplasmic binding partners, catenins. The cadherin/catenin adhesion system plays key roles in the morphogenesis and function of the vertebrate and invertebrate nervous systems. Furthermore, this system is involved in synaptic plasticity. Recent studies on the role of individual cadherin subtypes at synapses indicate that individual cadherin subtypes play their own unique role to regulate synaptic activities. Type II (atypical) cadherins are defined based on their lack of an HAV cell adhesion recognition sequence specific to type I cadherins. It has been observed that cells containing a specific cadherin subtype tend to cluster together to the exclusion of other types, both in cell culture and during development. Cadherin-12 also known as CDH12, is a type II classical cadherin from the cadherin superfamily of integral membrane proteins that mediate calcium-dependent cell-cell adhesion. Cadherin-12 appears to be expressed specifically in the brain and its temporal pattern of expression would be consistent with a role during a critical period of neuronal development, perhaps specifically during synaptogenesis.

CD46, also known as Membrane Cofactor Protein (MCP), is a complement regulatory protein. CD46 is a type 1 membrane protein that plays an important inhibitory role in the complement system. CD46 is expressed in white blood cells, platelets, epithelial cells, and fibroblasts. Human CD46 shares 5% amino acid sequence identity with mouse and rat CD46. The importance of CD46 to complement regulation is underscored by the observation that genetic loss of CD46 leads to development of atypical hemolytic-uremic syndrome (aHUS), a disease characterized by uncontrolled complement activation. CD46 is implicated in the development and/or progression of selected cancer types.

PAX8 gene is a member of the paired box (PAX) family of transcription factors. Members of this gene family typically encode proteins that contain a paired box domain, an octapeptide, and a paired-type homeodomain. PAX8 is involved in thyroid follicular cell development and expression of thyroid-specific genes. Also functions in very early stages of kidney organogenesis. Mutations in PAX8 gene have been associated with thyroid dysgenesis, thyroid follicular carcinomas and atypical follicular thyroid adenomas. Alternate transcriptional splice variants, encoding different isoforms, have been characterized.

Protein kinase C iota type, also known as Atypical protein kinase C-lambda/iota, aPKC-lambda/iota and PRKCI, is a cytoplasm, membrane and nucleus protein which belongs to the protein kinase superfamily, AGC Ser/Thr protein kinase family and PKC subfamily. PRKCI contains one AGC-kinase C-terminal domain, one OPR domain, one phorbol-ester/DAG-type zinc finger and one protein kinase domain. PRKCI is predominantly expressed in lung and brain, but also expressed at lower levels in many tissues including pancreatic islets. It is highly expressed in non-small cell lung cancers. PRKCI is a calcium-independent, phospholipid-dependent, serine- and threonine-specific kinase. It may play a role in the secretory response to nutrients. PRKCI is involved in cell polarization processes and the formation of epithelial tight junctions. It is implicated in the activation of several signaling pathways including Ras, c-Src and NF-kappa-B pathways. PRKCI functions in both pro- and anti-apoptotic pathways. It functions in the RAC1/ERK signaling required for transformed growth. PRKCI plays a role in microtubule dynamics through interaction with RAB2A and GAPDH and recruitment to vesicular tubular clusters (VTCs). PRKCI might be a target for novel lipid activators that are elevated during nutrient-stimulated insulin secretion.

Mouse Cxcl12 is a secreted and highly conserved protein which belongs to the intercrine alpha (chemokine CxC) family.CXCL12 is widely expressed in various organs including brain, kidney, skeletal muscle, heart, liver, and lymphoid organs. Cxcl12 activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions and chemotaxis. It also binds to atypical chemokine receptor ACKR3 which activates the beta-arrestin pathway and acts as a scavenger receptor for SDF-1. Cxcl12 has several critical functions during embryonic development such as B-cell lymphopoiesis, myelopoiesis in bone marrow and heart ventricular septum formation. Cxcl12 plays an important role in acting as a positive regulator of monocyte migration and a negative regulator of monocyte adhesion via the LYN kinase. It stimulates migration of monocytes and T-lymphocytes through its receptors, CXCR4 and ACKR3, and decreases monocyte adherence to surfaces coated with ICAM-1, a ligand for beta-2 integrins. SDF1A/CXCR4 signaling axis inhibits beta-2 integrin LFA-1 mediated adhesion of monocytes to ICAM-1 through LYN kinase. It also plays a protective role after myocardial infarction, induces down-regulation and internalization of ACKR3 expressed in various cells and stimulates the proliferation of bone marrow-derived b progenitor cells in the presence of IL-7 as well as growth of the stromal cell-dependent B-cell clone DW34 cells.

Complement factor H-related protein 5(FHR-5 for short), is a secreted protein which contains 9 Sushi (CCP/SCR) domains. It is expressed by the liver and secreted in plasma. The pattern of the deposits is similar to other complement components, suggesting that FHR-5 may play a role in complement activation and regulation. Defects in CFHR5 have been found in patients with atypical hemolytic uremic syndrome and may contribute to the disease. In contrast to typical hemolytic uremic syndrome, atypical forms have a poorer prognosis, with higher death rates and frequent progression to end-stage renal disease.

CD47, also known as Integrin‑Associated Protein (IAP) and OA3, is a glycosylated atypical member of the immunoglobulin superfamily. Mouse CD47 is an integral membrane protein that consists of a extracellular domain (ECD) with a single Ig‑like domain, five membrane-spanning regions with short intervening loops, and C‑terminal cytoplasmic tail. CD47 has a role in both cell adhesion by acting as an adhesion receptor for THBS1 on platelets, and in the modulation of integrins. It plays an important role in memory formation and synaptic plasticity in the hippocampus. As a receptor for SIRPA, it binding to which prevents maturation of immature dendritic cells and inhibits cytokine production by mature dendritic cells. Interaction with SIRPG mediates cellcell adhesion, it enhances superantigen-dependent T-cell-mediated proliferation and costimulates T-cell activation. It may play a role in membrane transport and/or integrin dependent signal transduction. It also prevents premature elimination of red blood cells.

Stathmin1 (STMN1) is a cytosolic phosphoprotein that regulates cellular microtubule dynamics and is known to have oncogenic activity. STMN1 is a possible biomarker for paclitaxel sensitivity and poor prognosis in GC and could be a novel therapeutic target in metastatic GC. STMN1 expression might serve as a biomarker for determining patient atypical meningioma prognosis. Stathmin1 (STMN1) is a cytosolic protein involved in microtubule dynamics through inhibition of tubulin polymerization and promotion of microtubule depolymerization, which has been implicated in carcinogenesis and aggressive behavior in multiple epithelial malignancies. Stathmin 1 (STMN1) suppression was reported to reduce cellular viability and migration potential. STMN1 may be a promising candidate for targeted therapies in PDAC.

RIOK1, also known as RIO kinase 1, is a member of the RIO family of atypical serine protein kinases first characterized in yeast. RIOK1 and RIOK2 proteins are present in organisms from Archaea to humans. RIOK1 functions as a new interactor of protein arginine methyltransferase 5 (PRMT5), competes with pICln for binding and modulates PRMT5 complex composition and substrate specificity. RioK1 and pICln bind to PRMT5 in a mutually exclusive fashion. This results in a PRMT5-WD45/MEP5 core structure that either associates with pICln or RioK1 RIOK1 in distinct complexes. RIOK1 functions in analogy to pICln as an adapter protein by recruiting the RNA-binding protein nucleolin to the PRMT5 complex for its symmetrical methylation.