Search results for STIM1

Showing 16 results out of 16

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Protein (1 results from a total of 1)

Identifier: R-HSA-434675
Species: Homo sapiens
Compartment: endoplasmic reticulum membrane
Primary external reference: UniProt: STIM1: Q13586

Reaction (6 results from a total of 6)

Identifier: R-HSA-1168376
Species: Homo sapiens
Compartment: endoplasmic reticulum membrane, endoplasmic reticulum lumen, cytosol
In the resting state the luminal domain of STIM1 binds Ca2+ ions within the endoplasmic reticulum and this binding prevents dimerization of STIM1 (Luik et al. 2008). Upon depletion of Ca2+ ions from the endoplasmic reticulum, STIM1 is no longer bound to Ca2+ and forms homodimers (Muik et al. 2008, Luik et al. 2008, Park et al. 2009).
Identifier: R-HSA-434700
Species: Homo sapiens
Compartment: plasma membrane
Sustained calcium signalling in lymphocytes and platelets requires the uptake of extracellular calcium when intracellular stores are depleted. The process whereby intracellular calcium depletion stimulates calcium uptake is often referred to as Store-operated calcium entry (SOCE). Store depletion is sensed by stromal interaction molecule 1 (STIM1), which then translocates to the plasma membrane and associates with 2 dimers of Orai to form a calcium-release activated calcium (CRAC) channel.
Identifier: R-HSA-2089927
Species: Homo sapiens
Compartment: endoplasmic reticulum membrane, plasma membrane
The polybasic region of STIM1 interacts with 2 aspartate residues in the C-terminal region of TRPC1 (Zeng et al. 2008, Huang et al. 2006). The STIM1:TRPC1 complex can form a tenary complex with ORAI1 (Ong et al. 2007, Jardin et al. 2008) and ORAI participates in function of STIM1:TRPC1 channels (Cheng et al. 2008, Cheng et al. 2011). As inferred from chicken DT40 cells, TRPC1 (and possibly other TRP channels) participates in store-operated calcium influx during signaling by the B cell receptor (Mori et al. 2002).
Identifier: R-HSA-2089943
Species: Homo sapiens
Compartment: cytosol, extracellular region, plasma membrane
TRPC1 forms a channel that transports Ca2+ across the plasma membrane. TRPC1 is gated by STIM1 (Ong et al. 2007).
Identifier: R-HSA-5626270
Species: Homo sapiens
Compartment: cytosol, extracellular region, plasma membrane
The five members of the NCKX (SLC24) family are all able to exchange one Ca2+ and one K+ for four Na+. SLC24A4 encodes an exchanger protein NCKX4 which may play a role in calcium transport during amelogenesis (the process of formation of tooth enamel). SLC24A4 is upregulated in ameloblasts during the maturation stage of amelogenesis. Defects in SLC24A4 can cause hypomineralised amelogenesis imperfecta (AI), an autosomal recessive disorder in which tooth enamel formation fails. Screening of AI families identified mutations which severely diminish or abolish transport function of SLC24A4. These mutations are R339*, S499C and A146V (Parry et al. 2013, Wang et al. 2014).
Identifier: R-HSA-9626848
Species: Homo sapiens
Compartment: phagocytic vesicle membrane, cytosol
Ca(2+) flux across the phagosomal membrane influences NADPH oxidase activity and ROS production. Phagocytic engagement of Fc gamma receptor (FcγR) or complement receptor 3 (CR3) activate phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), leading to the formation of PI(3,4,5)P3. This phospholipid participates in the activation of phospholipase γ C (PLCγ) and phospholipase D (PLD)-mediated downstream signaling pathways. The generation of IP3 by PLCγ triggers Ca(2+) release from intracellular stores (endoplasmic reticulum, ER) via the opening of IP3 receptors (IP3-R). PLD is involved in the process of sphingosine kinase-produced sphingosine 1-phosphate (S1P), leading to the depletion of intracellular Ca(2+) stores. The emptying of intracellular Ca2+ stores induces the activation of the Ca(2+) sensor stromal interaction molecule-1 (STIM1), which, in turn, activates calcium release-activated calcium channel protein 1 (ORAI1) at the plasma membrane and extracellular Ca(2+) entry. The resulting elevation of Ca(2+) mediates the recruitment of the cytosolic Ca(2+)-activated regulators S100A8 (also know as migration inhibitory factor-related proteins 8 (MRP8)) and S100A9 (MRP14) to the phagosomal membrane (Berthier S et al. 2003, 2012; Steinckwich N et al. 2011; Bréchard S et al. 2013). The translocation of S100A8:S100A9 allows the transfer of S100A9-binding arachidonic acid (AA) to cytochrome b558, favoring the conformational change of cytochrome b558 and promoting intraphagosomal NADPH oxidase activation and ROS production (Berthier S et al. 2003, 2012; Doussiere J et L. 2002; Kerkhoff C et al. 2005; Steinckwich N et al. 2011; Bréchard S et al. 2013 ). S100A8 & S100A9 exist mainly as a S100A8:S100A9 heterodimer which is termed calprotectin based on its role in innate immunity (Korndorfer IP et al. 2007). Ca(2+) is also known to stimulate formation of higher order oligomers of S100 proteins, including S100A8/S100A9 tetramers (Leukert N et al. 2006; Korndörfer IP et al. 2007). In addition, calprotectin has been shown to inhibit bacterial growth through chelation of extracellular manganese Mn(2+), zinc Zn(2+) and possibly iron Fe(2+) and thus restricting metal-ion availability during infection (Damo SM et al. 2013; Hayden JA et al. 2013; Brophy MB et al. 2013; Gagnon DM et al. 2015).

Complex (3 results from a total of 3)

Identifier: R-HSA-1168370
Species: Homo sapiens
Compartment: endoplasmic reticulum membrane
Identifier: R-HSA-2089954
Species: Homo sapiens
Compartment: plasma membrane
Identifier: R-HSA-1168371
Species: Homo sapiens
Compartment: endoplasmic reticulum membrane

Interactor (1 results from a total of 1)

Identifier: Q2M3R5
Species: Homo sapiens
Primary external reference: UniProt: Q2M3R5

Pathway (5 results from a total of 5)

Identifier: R-HSA-5619055
Species: Homo sapiens
The five members of the NCKX (SLC24) family are all able to exchange one Ca2+ and one K+ for four Na+. SLC24A4 encodes an exchanger protein NCKX4 which may play a role in calcium transport during amelogenesis (the process of formation of tooth enamel). SLC24A4 is upregulated in ameloblasts during the maturation stage of amelogenesis (Hu et al. 2012). Defects in SLC24A4 can cause hypomineralised amelogenesis imperfecta (AI), an autosomal recessive disorder in which tooth enamel formation fails. Screening of AI families identified mutations which severely diminish or abolish transport function of SLC24A4 (Parry et al. 2013, Wang et al. 2014).

Genetic variants in SLC24A4 define the skin/hair/eye pigmentation variation locus 6 (SHEP6; MIM:210750). In a genomewide association scan of thousands of Icelanders and Dutch, Sulem et al. found a strong association between the T allele of a SNP in the SLC24A4 gene and blond versus brown hair and blue versus green eyes (Sulem et al. 2007).
Identifier: R-HSA-983705
Species: Homo sapiens
Compartment: cytosol, extracellular region, plasma membrane
Mature B cells express IgM and IgD immunoglobulins which are complexed at the plasma membrane with Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) to form the B cell receptor (BCR) (Fu et al. 1974, Fu et al. 1975, Kunkel et al. 1975, Van Noesel et al. 1992, Sanchez et al. 1993, reviewed in Brezski and Monroe 2008). Binding of antigen to the immunoglobulin activates phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) in the cytoplasmic tails of Ig-alpha and Ig-beta by Src family tyrosine kinases, including LYN, FYN, and BLK (Nel et al. 1984, Yamanashi et al. 1991, Flaswinkel and Reth 1994, Saouaf et al. 1994, Hata et al. 1994, Saouaf et al. 1995, reviewed in Gauld and Cambier 2004, reviewed in Harwood and Batista 2010).
The protein kinase SYK binds the phosphorylated immunoreceptor tyrosine-activated motifs (ITAMs) on the cytoplasmic tails of Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) (Wienands et al. 1995, Rowley et al. 1995, Tsang et al. 2008). The binding causes the activation and autophosphorylation of SYK (Law et al. 1994, Baldock et al. 2000, Irish et al. 2006, Tsang et al. 2008, reviewed in Bradshaw 2010).
Activated SYK and other kinases phosphorylate BLNK (SLP-65), BCAP, and CD19 which serve as scaffolds for the assembly of large complexes, the signalosomes, by recruiting phosphoinositol 3-kinase (PI3K), phospholipase C gamma (predominantly PLC-gamma2 in B cells, Coggeshall et al. 1992), NCK, BAM32, BTK, VAV1, and SHC. The effectors are phosphorylated by SYK and other kinases.
PLC-gamma associated with BLNK hydrolyzes phosphatidylinositol-4,5-bisphosphate to yield inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (Carter et al. 1991, Kim et al. 2004). IP3 binds receptors on the endoplasmic reticulum and causes release of calcium ions from the ER into the cytosol. The depletion of calcium from the ER in turn activates STIM1 to interact with ORAI and TRPC1 channels in the plasma membrane, resulting in an influx of extracellular calcium ions (Muik et al. 2008, Luik et al. 2008, Park et al. 2009, Mori et al. 2002). PI3K associated with BCAP and CD19 phosphorylates phosphatidylinositol 4,5-bisphosphate to yield phosphatidyinositol 3,4,5-trisphosphate.
Second messengers (calcium, diacylglycerol, inositol 1,4,5-trisphosphate, and phosphatidylinositol 3,4,5-trisphosphate) trigger signaling pathways: NF-kappaB is activated via protein kinase C beta, RAS is activated via RasGRP proteins, NF-AT is activated via calcineurin, and AKT (PKB) is activated via PDK1 (reviewed in Shinohara and Kurosaki 2009, Stone 2006).
Identifier: R-HSA-983695
Species: Homo sapiens
Compartment: extracellular region, plasma membrane, cytosol
Mature B cells express IgM and IgD immunoglobulins which are complexed with Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) to form the B cell receptor (BCR) (Fu et al. 1974, Fu et al. 1975, Kunkel et al. 1975, Van Noesal et al. 1992, Sanchez et al. 1993, reviewed in Brezski and Monroe 2008). Binding of antigen to the immunoglobulin activates phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) in the cytoplasmic tails of Ig-alpha and Ig-beta by Src family tyrosine kinases, including LYN, FYN, and BLK (Nel et al. 1984, Yamanashi et al. 1991, Flaswinkel and Reth 1994, Saouaf et al. 1994, Hata et al. 1994, Saouaf et al. 1995, reviewed in Gauld and Cambier 2004, reviewed in Harwood and Batista 2010). The protein kinase SYK may also be involved in phosphorylating the ITAMs.
The protein kinase SYK binds the phosphorylated immunoreceptor tyrosine-activated motifs (ITAMs) on the cytoplasmic tails of Ig-alpha (CD79A, MB-1) and Ig-beta (CD79B, B29) (Wienands et al. 1995, Rowley et al. 1995, Tsang et al. 2008). The binding causes the activation and autophosphorylation of SYK (Law et al. 1994, Irish et al. 2006, Baldock et al. 2008, Tsang et al. 2008, reviewed in Bradshaw 2010).
Activated SYK and other kinases phosphorylate BLNK (SLP-65, BASH) and BCAP. LYN and FYN phosphorylate CD19. Phosphorylated BLNK, BCAP, and CD19 serve as scaffolds which recruit effectors to the plasma membrane and assemble large complexes, the signalosomes. BCAP and CD19 recruit phosphoinositol 3-kinase (PI3K). BLNK recruits phospholipase C gamma (predominantly PLC-gamma2 in B cells, Coggeshall et al. 1992), NCK, BAM32, BTK, VAV1, and SHC. The effectors are phosphorylated by SYK and other kinases.
Phosphorylated BCAP recruits PI3K, which is phosphorylated by a SYK-dependent mechanism (Kuwahara et al. 1996) and produces phosphatidylinositol-3,4,5-trisphosphate (PIP3). Phosphorylated CD19 likewise recruits PIP3K. PIP3 recruits BAM32 (Marshall et al. 2000) and BTK (de Weers et al. 1994, Baba et al. 2001) to the plasma membrane via their PH domains. PIP3 also recruits and activates PLC-gamma1 and PLC-gamma2 (Bae et al. 1998). BTK binds phosphorylated BLNK via its SH2 domain (Baba et al. 2001). BTK phosphorylates PLC-gamma2 (Rodriguez et al. 2001), which activates phospholipase activity (Carter et al. 1991, Roifman and Wang 1992, Kim et al. 2004, Sekiya et al. 2004). Phosphorylated BLNK recruits PLC-gamma, VAV, GRB2, and NCK (Fu and Chan 1997, Fu et al. 1998, Chiu et al. 2002).
PLC-gamma hydrolyzes phosphatidylinositol-4,5-bisphosphate to yield inositol-1,4,5-trisphosphate (IP3) and diacylglycerol (Carter et al. 1991, Kim et al. 2004). IP3 binds receptors on the endoplasmic reticulum and causes release of Ca2+ ions from the ER into the cytosol. The depletion of calcium from the ER in turn activates STIM1 to interact with ORAI and TRPC1 channels (and possibly other TRP channels) in the plasma membrane, resulting in an influx of extracellular calcium ions (Mori et al. 2002, Muik et al. 2008, Luik et al. 2008, Park et al. 2009).
Identifier: R-HSA-139853
Species: Homo sapiens
Compartment: cytosol
Activation of non- excitable cells involves the agonist-induced elevation of cytosolic Ca2+, an essential process for platelet activation. It occurs through Ca2+ release from intracellular stores and Ca2+ entry through the plasma membrane. Ca2+ store release involves phospholipase C (PLC)-mediated production of inositol-1,4,5-trisphosphate (IP3), which in turn stimulates IP3 receptor channels to release Ca2+ from intracellular stores. This is followed by Ca2+ entry into the cell through plasma membrane calcium channels, a process referred to as store-operated calcium entry (SOCE). Stromal interaction molecule 1 (STIM1), a Ca2+ sensor molecule in intracellular stores, and the four transmembrane channel protein Orai1 are the key players in platelet SOCE. Other major Ca2+ entry mechanisms are mediated by the direct receptor-operated calcium (ROC) channel, P2X1 and transient receptor potential channels (TRPCs).
Identifier: R-HSA-418360
Species: Homo sapiens
Ca2+ homeostasis is controlled by processes that elevate or counter the elevation of cytosolic Ca2+. During steady state conditions, cytoplasmic Ca2+ is reduced by the accumulation of Ca2+ in intracellular stores and by Ca2+ extrusion. The primary intracellular calcium store in platelets is the dense tubular system, the equivalent of the ER system in other cell types. Ca2+ is extruded by Ca2+-ATPases including plasma membrane Ca2+ ATPases (PMCAs) and sarco/endoplasmic reticulum Ca2+ -ATPase isoforms (SERCAs).

Activation of non- excitable cells involves the agonist-induced elevation of cytosolic Ca2+, an essential process for platelet activation. It occurs through Ca2+ release from intracellular stores and Ca2+ entry through the plasma membrane. Ca2+ store release involves phospholipase C (PLC)-mediated production of inositol-1,4,5-trisphosphate (IP3), which in turn stimulates IP3 receptor channels to release Ca2+ from intracellular stores. This is followed by Ca2+ entry into the cell through plasma membrane calcium channels, a process referred to as store-operated calcium entry (SOCE). Stromal interaction molecule 1 (STIM1), a Ca2+ sensor molecule in intracellular stores, and the four transmembrane channel protein Orai1 are the key players in platelet SOCE. Other major Ca2+ entry mechanisms are mediated by the direct receptor-operated calcium (ROC) channel, P2X1 and transient receptor potential channels (TRPCs).
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