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Immunoreceptor Tyrosine-based Inhibitory Motif
An immunoreceptor tyrosine-based inhibitory motif (ITIM), is a conserved sequence of amino acids that is found intracellularly in the cytoplasmic domains of many inhibitory receptors of the non-catalytic tyrosine-phosphorylated receptor family found on immune cells. These immune cells include T cells, B cells, NK cells, dendritic cells, macrophages and mast cells.  ITIMs have similar structures of S/I/V/LxYxxI/V/L, where x is any amino acid, Y is a tyrosine residue that can be phosphorylated, S is the amino acide Serine, I is the amino acid Isoleucine, and V is the amino acid Valine. ITIMs recruit SH2 domain-containing phosphatases, which inhibit cellular activation. ITIM-containing receptors often serve to target Immunoreceptor tyrosine-based activation motif(ITAM)-containing receptors, resulting in an innate inhibition mechanism within cells. ITIM bearing receptors have important role in regulation of immune system allowing negative regulation at different levels of the immune re ...
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Amino Acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha amino acids appear in the genetic code. Amino acids can be classified according to the locations of the core structural functional groups, as Alpha and beta carbon, alpha- , beta- , gamma- or delta- amino acids; other categories relate to Chemical polarity, polarity, ionization, and side chain group type (aliphatic, Open-chain compound, acyclic, aromatic, containing hydroxyl or sulfur, etc.). In the form of proteins, amino acid '' residues'' form the second-largest component (water being the largest) of human muscles and other tissues. Beyond their role as residues in proteins, amino acids participate in a number of processes such as neurotransmitter transport and biosynthesis. It is thought that they played a key role in enabling l ...
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SHIP1
Src homology 2 (SH2) domain containing inositol polyphosphate 5-phosphatase 1 (SHIP1) is an enzyme with phosphatase activity. SHIP1 is structured by multiple domain and is encoded by the ''INPP5D'' gene in humans. SHIP1 is expressed predominantly by hematopoietic cells but also, for example, by osteoblasts and endothelial cells. This phosphatase is important for the regulation of cellular activation. Not only catalytic but also adaptor activities of this protein are involved in this process. Its movement from the cytosol to the cytoplasmic membrane, where predominantly performs its function, is mediated by tyrosine phosphorylation of the intracellular chains of cell surface receptors that SHIP1 binds. Insufficient regulation of SHIP1 leads to different pathologies. Structure and regulation of activity SHIP1 is a 145 kDa large protein and member of the inositol polyphosphate-5-phosphatase (INPP5) family. Alternate transcriptional splice variants, encoding different isoforms, ...
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Signal-regulatory Protein Alpha
Signal regulatory protein α (SIRPα) is a regulatory membrane glycoprotein from SIRP family expressed mainly by myeloid cells and also by stem cells or neurons. SIRPα acts as inhibitory receptor and interacts with a broadly expressed transmembrane protein CD47 also called the "don't eat me" signal. This interaction negatively controls effector function of innate immune cells such as host cell phagocytosis. SIRPα diffuses laterally on the macrophage membrane and accumulates at a phagocytic synapse to bind CD47 and signal 'self', which inhibits the cytoskeleton-intensive process of phagocytosis by the macrophage. This is analogous to the self signals provided by MHC class I molecules to NK cells via Ig-like or Ly49 receptors. NB. Protein shown to the right is CD47 not SIRP α. Structure The cytoplasmic region of SIRPα is highly conserved between rats, mice and humans. Cytoplasmic region contains a number of tyrosine residues, which likely act as ITIMs. Upon CD47 ligation, S ...
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CD72
CD7 (Cluster of Differentiation 7) is a protein that in humans is encoded by the ''CD7'' gene. Function This gene encodes a transmembrane protein which is a member of the immunoglobulin superfamily. This protein is found on thymocytes and mature T cells. It plays an essential role in T-cell interactions and also in T-cell/B-cell interaction during early lymphoid development. See also * Cluster of differentiation Interactions CD7 has been shown to interact with PIK3R1. Clinical significance CD7 can be aberrantly expressed in refractory anaemia with excess blasts (RAEB) and may confer a worse prognosis. Also, a lack of CD7 expression could insinuate mycosis fungoides Mycosis fungoides, also known as Alibert-Bazin syndrome or granuloma fungoides, is the most common form of cutaneous T-cell lymphoma. It generally affects the skin, but may progress internally over time. Symptoms include rash, tumors, skin lesions ... (MF) or Sezary syndrome (SS). References Further r ...
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CD22
CD22, or cluster of differentiation-22, is a molecule belonging to the SIGLEC family of lectins. It is found on the surface of mature B cells and to a lesser extent on some immature B cells. Generally speaking, CD22 is a regulatory molecule that prevents the overactivation of the immune system and the development of autoimmune diseases. CD22 is a sugar binding transmembrane protein, which specifically binds sialic acid with an immunoglobulin (Ig) domain located at its N-terminus. The presence of Ig domains makes CD22 a member of the immunoglobulin superfamily. CD22 functions as an inhibitory receptor for B cell receptor (BCR) signaling. It is also involved in the B cell trafficking to Peyer's patches in mice. In mice, it has been shown that CD22 blockade restores homeostatic microglial phagocytosis in aging brains. Structure CD22 is a transmembrane protein with a molecular weight of 140 kDa. The extracellular part of CD22 consists of seven immunoglobulin domains and the int ...
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LAIR1
Leukocyte-associated immunoglobulin-like receptor 1 is a protein that in humans is encoded by the ''LAIR1'' gene. LAIR1 has also been designated as CD305 (cluster of differentiation 305). Function The protein encoded by this gene is an inhibitory receptor found on peripheral mononuclear cells, including NK cells, T cells, and B cells. Inhibitory receptors regulate the immune response to prevent lysis of cells recognized as self. The gene is a member of both the immunoglobulin superfamily and the leukocyte-associated inhibitory receptor family. The gene maps to a region of 19q13.4 called the leukocyte receptor cluster, which contains at least 29 genes encoding leukocyte-expressed receptors of the immunoglobulin superfamily. Interactions LAIR1 has been shown to interact with PTPN11 and PTPN6 Tyrosine-protein phosphatase non-receptor type 6, also known as Src homology region 2 domain-containing phosphatase-1 (SHP-1), is an enzyme that in humans is encoded by the ''PTPN6'' ...
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Ly49
Ly49 is a family of membrane C-type lectin-like receptors expressed mainly on NK cells but also on other immune cells (some CD8+ and CD3+ T lymphocytes, intestinal epithelial lymphocytes (IELs), NKT cells, uterine NK cells (uNK) cells, macrophages or dendritic cells). Their primary role is to bind MHC-I molecules to distinguish between self healthy cells and infected or altered cells. Ly49 family is coded by Klra gene cluster and include genes for both inhibitory and activating paired receptors, but most of them are inhibitory. Inhibitory Ly49 receptors play a role in the recognition of self cells and thus maintain self-tolerance and prevent autoimmunity by suppressing NK cell activation. On the other hand, activating receptors recognise ligands from cancer or viral infected cells (induced-self hypothesis) and are used when cells lack or have abnormal expression of MHC-I molecules (missing-self hypothesis), which activate cytokine production and cytotoxic activity of NK and immune ...
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Killer-cell Immunoglobulin-like Receptor
Killer-cell immunoglobulin-like receptors (KIRs), are a family of type I transmembrane glycoproteins expressed on the plasma membrane of natural killer (NK) cells and a minority of T cells. At least 15 genes and 2 pseudogenes encoding KIR map in a 150-kb region of the leukocyte receptor complex (LRC) on human chromosome 19q13.4. They regulate the killing function of these cells by interacting with major histocompatibility (MHC) class I molecules, which are expressed on all nucleated cell types. KIR receptors can distinguish between MHC I allelic variants, which allows them to detect virally infected cells or transformed cells. KIRs are paired receptors with both activating and inhibitory functions; most KIRs are inhibitory: their recognition of MHC molecules suppresses the cytotoxic activity of their NK cell. A limited number of KIRs are activating: their recognition of MHC molecules activates the cytotoxic activity of their cell. Initial expression of KIRs on NK cell ...
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PTPN11
Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) also known as protein-tyrosine phosphatase 1D (PTP-1D), Src homology region 2 domain-containing phosphatase-2 (SHP-2), or protein-tyrosine phosphatase 2C (PTP-2C) is an enzyme that in humans is encoded by the ''PTPN11'' gene. PTPN11 is a protein tyrosine phosphatase (PTP) Shp2. PTPN11 is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains two tandem Src homology-2 domains, which function as phospho-tyrosine binding domains and mediate the interaction of this PTP with its substrates. This PTP is widely expressed in most tissues and plays a regulatory role in various cell signaling events that are important for a diversity of cell functions, such as mitogenic activation, metabolic control, transcription regulation, and cell migrati ...
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PTPN6
Tyrosine-protein phosphatase non-receptor type 6, also known as Src homology region 2 domain-containing phosphatase-1 (SHP-1), is an enzyme that in humans is encoded by the ''PTPN6'' gene. Function The protein encoded by this gene is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. N-terminal part of this PTP contains two tandem Src homolog ( SH2) domains, which act as protein phospho-tyrosine binding domains, and mediate the interaction of this PTP with its substrates. This PTP is expressed primarily in hematopoietic cells, and functions as an important regulator of multiple signaling pathways in hematopoietic cells. This PTP has been shown to interact with, and dephosphorylate a wide spectrum of phospho-proteins involved in hematopoietic cell signaling, (e.g., the LYN-CD22- SHP-1 pathway). Multiple ...
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Haematopoiesis
Haematopoiesis (, from Greek , 'blood' and 'to make'; also hematopoiesis in American English; sometimes also h(a)emopoiesis) is the formation of blood cellular components. All cellular blood components are derived from haematopoietic stem cells. In a healthy adult person, approximately – new blood cells are produced daily in order to maintain steady state levels in the peripheral circulation.Semester 4 medical lectures at Uppsala University 2008 by Leif Jansson Process Haematopoietic stem cells (HSCs) Haematopoietic stem cells (HSCs) reside in the medulla of the bone (bone marrow) and have the unique ability to give rise to all of the different mature blood cell types and tissues. HSCs are self-renewing cells: when they differentiate, at least some of their daughter cells remain as HSCs so the pool of stem cells is not depleted. This phenomenon is called asymmetric division. The other daughters of HSCs (myeloid and lymphoid progenitor cells) can follow any of the oth ...
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Shp-2
Tyrosine-protein phosphatase non-receptor type 11 (PTPN11) also known as protein-tyrosine phosphatase 1D (PTP-1D), Src homology region 2 domain-containing phosphatase-2 (SHP-2), or protein-tyrosine phosphatase 2C (PTP-2C) is an enzyme that in humans is encoded by the ''PTPN11'' gene. PTPN11 is a protein tyrosine phosphatase (PTP) Shp2. PTPN11 is a member of the protein tyrosine phosphatase (PTP) family. PTPs are known to be signaling molecules that regulate a variety of cellular processes including cell growth, differentiation, mitotic cycle, and oncogenic transformation. This PTP contains two tandem Src homology-2 domains, which function as phospho-tyrosine binding domains and mediate the interaction of this PTP with its substrates. This PTP is widely expressed in most tissues and plays a regulatory role in various cell signaling events that are important for a diversity of cell functions, such as mitogenic activation, metabolic control, transcription regulation, and cell migratio ...
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