Search results for VAPA

Showing 16 results out of 18

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Protein (4 results from a total of 4)

Identifier: R-HSA-429677
Species: Homo sapiens
Compartment: endoplasmic reticulum membrane
Primary external reference: UniProt: VAPA: Q9P0L0
Identifier: R-HSA-6799364
Species: Homo sapiens
Compartment: azurophil granule membrane
Primary external reference: UniProt: VAPA: Q9P0L0
Identifier: R-HSA-6806269
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: VAPA: Q9P0L0
Identifier: R-HSA-9609920
Species: Homo sapiens
Compartment: cytosol
Primary external reference: UniProt: VAPA: Q9P0L0

RNA Sequence (1 results from a total of 1)

Identifier: R-HSA-8945712
Species: Homo sapiens
Compartment: cytosol
Primary external reference: ENSEMBL: ENSEMBL:ENST00000340541

Reaction (6 results from a total of 8)

Identifier: R-HSA-8948582
Species: Homo sapiens
Compartment: cytosol
MicroRNA miR-17 binds the VAPA mRNA. VAPA mRNA acts as a competing endogenous RNA (ceRNA) for PTEN, preventing binding of miR-17 microRNA to PTEN mRNA and PTEN downregulation (Tay et al. 2011).
Identifier: R-HSA-8948621
Species: Homo sapiens
Compartment: cytosol
MicroRNAs miR-20a and miR-20b bind the VAPA mRNA. VAPA mRNA acts as a competing endogenous RNA (ceRNA) for PTEN, preventing binding of miR-20 microRNAs to PTEN mRNA and PTEN downregulation (Tay et al. 2011).
Identifier: R-HSA-8948594
Species: Homo sapiens
Compartment: cytosol
MicroRNA miR-19a binds the VAPA mRNA. VAPA mRNA acts as a competing endogenous RNA (ceRNA) for PTEN, preventing binding of miR-19a microRNA to PTEN mRNA and PTEN downregulation (Tay et al. 2011).
Identifier: R-HSA-8948641
Species: Homo sapiens
Compartment: cytosol
MicroRNAs miR-106a and miR-106b bind the VAPA mRNA. VAPA mRNA acts as a competing endogenous RNA (ceRNA) for PTEN, preventing binding of miR-106 microRNAs to PTEN mRNA and PTEN downregulation (Tay et al. 2011).
Identifier: R-HSA-429732
Species: Homo sapiens
Compartment: cytosol, endoplasmic reticulum membrane
Multiphospho-CERT retains its affinity for VAPA or VAPB (VAMP-associated proteins A or B) and PPM1L (protein phosphatase 1-like) in the endoplasmic reticulum membrane, and can associate with them to form a membrane-associated complex (Kawano et al., 2006; Saito et al. 2008; reviewed by Kumagai & Hanada, 2019).
Identifier: R-HSA-429694
Species: Homo sapiens
Compartment: cytosol, endoplasmic reticulum membrane
CERT1-2 (ceramide transfer protein, isoform 2) can dissociate from its complex in the endoplasmic reticulum membrane with VAPA or VAPB (VAMP-associated proteins A or B) and PPM1L (protein phosphatase 1-like) and is released into the cytosol (Kawano et al. 2006; reviewed by Kumagai & Hanada, 2019).

Set (1 results from a total of 1)

Identifier: R-HSA-429670
Species: Homo sapiens
Compartment: endoplasmic reticulum membrane

Pathway (4 results from a total of 4)

Identifier: R-HSA-8948700
Species: Homo sapiens
Coding and non-coding RNAs can prevent microRNAs from binding to PTEN mRNA. These RNAs are termed competing endogenous RNAs or ceRNAs. Transcripts of the pseudogene PTENP1 and mRNAs transcribed from SERINC1, VAPA and CNOT6L genes exhibit this activity (Poliseno et al. 2010, Tay et al. 2011, Tay et al. 2014). SERINC1 mRNA will be annotated in this context when additional experimental details become available.
Identifier: R-HSA-8943723
Species: Homo sapiens
MicroRNAs miR-17, miR-19a, miR-19b, miR-20a, miR-20b, miR-21, miR-22, miR-25, miR 26A1, miR 26A2, miR-93, miR-106a, miR-106b, miR 205, and miR 214 and bind PTEN mRNA and inhibit its translation into protein. These microRNAs are altered in cancer and can account for changes in PTEN levels. There is evidence that PTEN mRNA translation is also inhibited by other microRNAs, such as miR-302 and miR-26B, and these microRNAs will be annotated when additional experimental details become available (Meng et al. 2007, Xiao et al. 2008, Yang et al. 2008, Huse et al. 2009, Kim et al. 2010, Poliseno, Salmena, Riccardi et al. 2010, Zhang et al. 2010, Tay et al. 2011, Qu et al. 2012, Cai et al. 2013). In addition, coding and non coding RNAs can prevent microRNAs from binding to PTEN mRNA. These RNAs are termed competing endogenous RNAs or ceRNAs. Transcripts of the pseudogene PTENP1 and mRNAs transcribed from SERINC1, VAPA and CNOT6L genes exhibit this activity (Poliseno, Salmena, Zhang et al. 2010, Tay et al. 2011, Tay et al. 2014).
Identifier: R-HSA-428157
Species: Homo sapiens
Sphingolipids are derivatives of long chain sphingoid bases such as sphingosine (trans-1,3-dihydroxy 2-amino-4-octadecene), an 18-carbon unsaturated amino alcohol which is the most abundant sphingoid base in mammals. Amide linkage of a fatty acid to sphingosine yields ceramides. Esterification of phosphocholine to ceramides yields sphingomyelin, and ceramide glycosylation yields glycosylceramides. Introduction of sialic acid residues yields gangliosides. These molecules appear to be essential components of cell membranes, and intermediates in the pathways of sphingolipid synthesis and breakdown modulate processes including apoptosis and T cell trafficking.

While sphingolipids are abundant in a wide variety of foodstuffs, these dietary molecules are mostly degraded by the intestinal flora and intestinal enzymes. The body primarily depends on de novo synthesis for its sphingolipid supply (Hannun and Obeid 2008; Merrill 2002). De novo synthesis proceeds in four steps: the condensation of palmitoyl-CoA and serine to form 3-ketosphinganine, the reduction of 3-ketosphinganine to sphinganine, the acylation of sphinganine with a long-chain fatty acyl CoA to form dihydroceramide, and the desaturation of dihydroceramide to form ceramide.

Other sphingolipids involved in signaling are derived from ceramide and its biosynthetic intermediates. These include sphinganine (dihydrosphingosine) 1-phosphate, phytoceramide, sphingosine, and sphingosine 1-phosphate.

Sphingomyelin is synthesized in a single step in the membrane of the Golgi apparatus from ceramides generated in the endoplasmic reticulum (ER) membrane and transferred to the Golgi by CERT (ceramide transfer protein), an isoform of COL4A3BP that is associated with the ER membrane as a complex with PPM1L (protein phosphatase 1-like) and VAPA or VAPB (VAMP-associated proteins A or B). Sphingomyelin synthesis appears to be regulated primarily at the level of this transport process through the reversible phosphorylation of CERT (Saito et al. 2008).

Identifier: R-HSA-6807070
Species: Homo sapiens
PTEN is regulated at the level of gene transcription, mRNA translation, localization and protein stability.

Transcription of the PTEN gene is regulated at multiple levels. Epigenetic repression involves the recruitment of Mi-2/NuRD upon SALL4 binding to the PTEN promoter (Yang et al. 2008, Lu et al. 2009) or EVI1-mediated recruitment of the polycomb repressor complex (PRC) to the PTEN promoter (Song et al. 2009, Yoshimi et al. 2011). Transcriptional regulation is also elicited by negative regulators, including NR2E1:ATN1 (atrophin-1) complex, JUN (c-Jun), SNAIL and SLUG (Zhang et al. 2006, Vasudevan et al. 2007, Escriva et al. 2008, Uygur et al. 2015) and positive regulators such as TP53 (p53), MAF1, ATF2, EGR1 or PPARG (Stambolic et al. 2001, Virolle et al. 2001, Patel et al. 2001, Shen et al. 2006, Li et al. 2016).

MicroRNAs miR-26A1, miR-26A2, miR-22, miR-25, miR-302, miR-214, miR-17-5p, miR-19 and miR-205 bind PTEN mRNA and inhibit its translation into protein. These microRNAs are altered in cancer and can account for changes in PTEN levels (Meng et al. 2007, Xiao et al. 2008, Yang et al. 2008, Huse et al. 2009, Kim et al. 2010, Poliseno, Salmena, Riccardi et al. 2010, Cai et al. 2013). In addition, coding and non-coding RNAs can prevent microRNAs from binding to PTEN mRNA. These RNAs are termed competing endogenous RNAs or ceRNAs. Transcripts of the pseudogene PTENP1 and mRNAs transcribed from SERINC1, VAPA and CNOT6L genes exhibit this activity (Poliseno, Salmena, Zhang et al. 2010, Tay et al. 2011, Tay et al. 2014).

PTEN can translocate from the cytosol to the nucleus after undergoing monoubiquitination. PTEN's ability to localize to the nucleus contributes to its tumor suppressive role (Trotman et al. 2007). The ubiquitin protease USP7 (HAUSP) targets monoubiquitinated PTEN in the nucleus, resulting in PTEN deubiquitination and nuclear exclusion. PML, via an unknown mechanism that involves USP7- and PML-interacting protein DAXX, inhibits USP7-mediated deubiquitination of PTEN, thus promoting PTEN nuclear localization. Disruption of PML function in acute promyelocytic leukemia, through a chromosomal translocation that results in expression of a fusion protein PML-RARA, leads to aberrant PTEN localization (Song et al. 2008).

Several ubiquitin ligases, including NEDD4, WWP2, STUB1 (CHIP), RNF146, XIAP and MKRN1, polyubiquitinate PTEN and target it for proteasome-mediated degradation (Wang et al. 2007, Van Themsche et al. 2009, Ahmed et al. 2011, Maddika et al. 2011, Lee et al. 2015, Li et al. 2015). The ubiquitin proteases USP13 and OTUD3, frequently down-regulated in breast cancer, remove polyubiquitin chains from PTEN, thus preventing its degradation and increasing its half-life (Zhang et al. 2013, Yuan et al. 2015). The catalytic activity of PTEN is negatively regulated by PREX2 binding (Fine et al. 2009, Hodakoski et al. 2014) and TRIM27-mediated ubiquitination (Lee et al. 2013), most likely through altered PTEN conformation.

In addition to ubiquitination, PTEN also undergoes SUMOylation (Gonzalez-Santamaria et al. 2012, Da Silva Ferrada et al. 2013, Lang et al. 2015, Leslie et al. 2016). SUMOylation of the C2 domain of PTEN may regulate PTEN association with the plasma membrane (Shenoy et al. 2012) as well as nuclear localization of PTEN (Bassi et al. 2013, Collaud et al. 2016). PIASx-alpha, a splicing isorom of E3 SUMO-protein ligase PIAS2 has been implicated in PTEN SUMOylation (Wang et al. 2014). SUMOylation of PTEN may be regulated by activated AKT (Lin et al. 2016). Reactions describing PTEN SUMOylation will be annotated when mechanistic details become available.

Phosphorylation affects the stability and activity of PTEN. FRK tyrosine kinase (RAK) phosphorylates PTEN on tyrosine residue Y336, which increases PTEN half-life by inhibiting NEDD4-mediated polyubiquitination and subsequent degradation of PTEN. FRK-mediated phosphorylation also increases PTEN enzymatic activity (Yim et al. 2009). Casein kinase II (CK2) constitutively phosphorylates the C-terminal tail of PTEN on serine and threonine residues S370, S380, T382, T383 and S385. CK2-mediated phosphorylation increases PTEN protein stability (Torres and Pulido 2001) but results in ~30% reduction in PTEN lipid phosphatase activity (Miller et al. 2002).

PTEN localization and activity are affected by acetylation of its lysine residues (Okumura et al. 2006, Ikenoue et al. 2008, Meng et al. 2016). PTEN can undergo oxidation, which affects its function, but the mechanism is poorly understood (Tan et al. 2015, Shen et al. 2015, Verrastro et al. 2016).

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