Search results for CHIA

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Protein (1 results from a total of 1)

Identifier: R-HSA-6786395
Species: Homo sapiens
Compartment: extracellular region
Primary external reference: UniProt: CHIA: Q9BZP6

Reaction (6 results from a total of 23)

Identifier: R-HSA-6786421
Species: Homo sapiens
Compartment: extracellular region
Chitin is a linear polymer made up of repeating units of the sugar N-acetylglucosamine (GlcNAc) and is the second most abundant polysaccharide in nature after cellulose. It is found in the cell walls of bacteria and fungi, the exoskeleton of crustaceans and insects, and the microfilarial sheath of parasitic nematodes. Chitinases are evolutionarily ancient enzymes that hydrolyse the chitin polymer into di- and trisaccharides. This process produces differentially sized chitin fragments that can trigger the release of type 2 cytokines, including interleukin IL-4, IL-5, IL-13 by CD4 T helper (Th2) and other immune cells which play critical roles in the pathogenesis of asthma and allergic responses. Humans express two active chitinases; acidic mammalian chitinase (CHIA, AMCase) and chitotriosidase (CHIT1) . CHIA is a secreted enzyme that can randomly hydrolyse chitin (and chitotriose, not shown here) (Boot et al. 2001, Chou et al. 2006, Harti et al. 2008, Olland et al. 2009, Seibold et al. 2009).
Identifier: R-HSA-6814674
Species: Homo sapiens
Compartment: trans-Golgi network membrane
RAB9 positive vesicles from the late endosomes are tethered at the trans-Golgi network (TGN) through interaction with the GARP complex, the TGN-specific Golgin GCC2 and a t-SNARE complex consisting of STX10, STX16 and VTI1A (Hayes et al, 2009; Derby et al, 2007; Reddy et al, 2006; Ganley et al, 2008; Perez-Victoria et al, 2009; Lombardi et al, 1993; Lieu et al, 2007; reviewed in Chia and Gleeson, 2014)
Identifier: R-HSA-1112609
Species: Homo sapiens
Compartment: nucleoplasm
POU5F1 (OCT4), SOX2, and NANOG bind distinct sites in the promoter of the POU5F1 gene (Boyer et al. 2005, Chew et al. 2005, Rodda et al. 2005, Jin et al. 2007, Lister et al. 2009, Jung et al. 2010, Goke et al. 2011). The set of target genes of POU5F1, SOX2, and NANOG includes POU5F1, SOX2, and NANOG themselves, thus their expression is a component of an autoregulatory loop . Activin/Nodal signaling also regulates POU5F1 transcription via SMAD2 and SMAD3 (Brown et al. 2011). PRDM14 binds the POU5F1 promoter and regulates transcription (Chia et al. 2010).
Identifier: R-HSA-8876191
Species: Homo sapiens
Compartment: trans-Golgi network membrane, cytosol
RAB9 plays a role in the retrograde traffic of cargo such as the mannose-6-phosphate receptors (M6PR) from the late endosome to the trans-Golgi network (TGN). Vesicles are recruited to the TGN through interaction of RAB9 with the atypical RHO GTPase RHOBTB3, and tethered by virtue of interaction with TGN-localized Golgins and the GARP complex (Perez-Victoria et al, 2008; Perez-Victoria et al, 2009; Diaz et al, 1999; Espinosa et al, 2009; reviewed in Pfeffer, 2011; Chia and Gleeson, 2014). Interaction of RAB9:GDP with its GEFs promotes release of GDP, allowing GTP to bind, and precludes the interaction of RAB9 with GDI and CHM proteins. DENND2 family members have been shown to be RAB9 specific GEFs, and HeLa cells depleted of RAB9 or DENND2A show reduced staining of M6PR and a loss of M6PR-positive structures in the cell periphery (Yoshimura et al, 2010).
Identifier: R-HSA-452392
Species: Homo sapiens
Compartment: nucleoplasm, cytosol
The POU5F1 (OCT4) gene is transcribed to yield mRNA and the mRNA is translated to yield protein (Rao et al. 2004, Richards et al. 2004, Cauffman et al. 2005, Tai et al. 2005, Gerrard et al. 2005, Li et al. 2006, Adewumi et al. 2007,Assou etal. 2007). POU5F1 mRNA and protein are found in the cytoplasm of oocytes and cleavage-stage embryos (Cauffman et al. 2005). POU5F1 protein becomes nuclear during compaction, and protein and mRNA are present in inner cell mass and trophectoderm (Cauffman et al. 2005). Transcripts are also detectable in some differentiated tissues (Cauffman et al. 2005). POU5F1 is expressed in adult stem cells and cancers (Tai et al. 2005). POU5F1, SOX2, NANOG, SALL4, and SF-1(NR5A1) bind the promoter of the POU5F1 gene and enhance transcription (Matin et al. 2004, Chew et al. 2005, Boyer et al. 2005, Babaie et al. 2007, Greber et al. 2007, Wang et al. 2007, Yang et al. 2010, Chia et al. 2010). POU5F1 and SOX2 bind adjacent sites at the promoter and form a heterodimer on the DNA. SALL4 binds the promoter of the POU5F1 gene and activates transcription of POU5F1 (Yang et al. 2010). POU5F1 activates SALL4 expression thus forming a self-reinforcing loop. Activation-induced cytidine deaminase (AID) binds the methylated promoter of the POU5F1 gene, demethylates it, and enhances expression of POU5F1 (Bhutani et al. 2009). Hypoxia acts via HIF3A and EPAS1 (HIF2A) to enhance expression of POU5F1 (Forristal et al. 2010). LIN28 binds the POU5F1 mRNA and increases translation (Qiu et al. 2009).
Identifier: R-HSA-480204
Species: Homo sapiens
Compartment: nucleoplasm
KLF4, PBX1, POU5F1 (OCT4), SOX2, and NANOG bind the promoter of the NANOG gene and enhance expression of NANOG (Rodda et al. 2005, Boyer et al. 2005, Babaie et al. 2007, Jin et al. 2007, Chan et al. 2009, Vallier et al. 2009, Jung et al. 2011). In mouse Nanog has been shown to repress its own expression (Fidalgo et al. 2012, Navarro et al. 2012). ZIC3, a NANOG target, also positively regulates NANOG expression, possibly by binding the NANOG promoter and activating transcription (Lim et al. 2007). Activin/Nodal signaling regulates NANOG via SMAD2 and SMAD3 (Brown et al. 2011)

Person (1 results from a total of 1)

Authored Pathways: 0
Reviewed Pathways: 1
Authored Reactions: 0
Reviewed Reactions: 26

Pathway (6 results from a total of 7)

Identifier: R-HSA-6811438
Species: Homo sapiens
The mammalian Golgi consists of at least three biochemically distinct cisternae, cis-, medial- and trans (reviewed in Szul and Sztul, 2011; Day et al, 2013). The structure and function of the Golgi are tightly interconnected, such that proteins that are required for protein transport through the Golgi are often also required for the organization of the Golgi stacks, and vice versa (reviewed in Liu and Storrie, 2012; Liu and Storrie, 2015; Chia and Gleeson, 2014; Munro, 2011). Newly synthesized proteins from the ER and ERGIC are received at the cis face of the Golgi and flow through to the trans-Golgi before being released to the trans-Golgi network (TGN) for further secretion to the endolysosomal system, plasma membrane or extracellular region. Retrograde flow from the trans- to cis-cisternae moves endocytosed cargo from the extracellular region, the plasma membrane and the endolysosomal system back towards the ER. Intra-Golgi retrograde traffic also returns resident Golgi proteins to their appropriate cisternae, in this way facilitating cisternal remodeling or maturation (reviewed in Boncompain and Perez, 2013; Day et al, 2013). Intra-Golgi traffic in both directions is mediated by COPI carriers, with specificity of transport being determined at least in part by the complement of SNAREs, RABs and tethering proteins involved (reviewed in Szul and Sztul, 2011; Spang 2013; Willet et al, 2013; Chia and Gleeson, 2014).
Identifier: R-HSA-6811440
Species: Homo sapiens
The trans-Golgi network is the docking site for retrograde cargo from the endolysosomal system and the plasma membrane. Typical cargo includes recycling resident TGN proteins such as TGOLN2 (also known as TGN46), receptors such as the mannose-6-phosphate receptors and toxins like Shiga, cholera and ricin which use the retrograde trafficking machinery to 'hitchhike' back through the secretory system for release into the cytoplasm (reviewed in Johannes and Popoff, 2008; Pfeffer, 2011; Sandvig et al, 2013). These cargo are trafficked from the endocytic system in a clathrin- and AP1-dependent manner that is described in more detail in the "Trans-Golgi network budding pathway" (just not yet). In general, it appears that vesicles are uncoated prior to their tethering and fusion at the TGN. At the TGN, at least 2 distinct tethering pathways exist. A RAB6-dependent pathway contributes to the fusion and docking of vesicles from the early endocytic pathway. These vesicles, which carry cargo such as TGOLN2 and toxins, dock at the TGN through interactions with TGN-localized Golgin tethers and with the multisubunit tethering complexes COG and GARP (reviewed in Bonafacino and Rojas, 2006; Bonafacino and Hierro, 2011; Pfeffer, 2011). In contrast, mannose-6-phosphate receptors appear to traffic from late endosomes to the TGN through a RAB9- and PLIN3-dependent pathway. Vesicles are recruited to the TGN through interaction of RAB9 with the atypical RHO GTPase RHOBTB3, and tethered by virtue of interaction with TGN-localized Golgins and the GARP complex (Perez-Victoria et al, 2008; Perez-Victoria et al, 2009; Diaz et al, 1999; reviewed in Pfeffer, 2011; Chia and Gleeson, 2014)
Identifier: R-HSA-6811442
Species: Homo sapiens
The mammalian Golgi complex, a central hub of both anterograde and retrograde trafficking, is a ribbon of stacked cisterna with biochemically distinct compartments (reviewed in Glick and Nakano, 2009; Szul and Sztul, 2011). Anterograde cargo from the ERGIC and ER is received at the cis-Golgi, trafficked through the medial- and trans-Golgi and released through the trans-Golgi network (TGN) to the endolysosomal system and the plasma membrane. Although still under debate, current models of Golgi trafficking favour the cisternal maturation model, where anterograde cargo remain associated with their original lipid membrane during transit through the Golgi and are exposed to sequential waves of processing enzymes by the retrograde movement of Golgi resident proteins. In this way, cis-cisterna mature to medial- and trans-cisterna as the early acting Golgi enzymes are replaced by later acting ones (reviewed in Pelham, 2001; Storrie, 2005; Glick and Nakano, 2009; Szul and Sztul, 2011). More recently. a kiss-and-run (KAR) model for intra-Golgi trafficking has been proposed, which marries aspects of the cisternal maturation model with a diffusion model of transport (reviewed in Mironov et al, 2103).
Like the anterograde ERGIC-to Golgi transport step, intra-Golgi trafficking between the cisterna appears to be COPI-dependent (Storrie and Nilsson, 2002; Szul and Sztul, 2011). Numerous snares and tethering complexes contribute to the targeting and fusion events that are required to maintain the specificity and directionality of these trafficking events (reviewed in Chia and Gleeson, 2014). Golgi tethers include long coiled coiled proteins like the Golgins, as well as multisubunit tethers like the COG complex. These tethers make numerous interactions with other components of the secretory system including RABs, SNAREs, motor and coat proteins as well as components of the cytoskeleton (reviewed in Munro, 2011; Willet et al, 2013).
Retrograde traffic from the cis-Golgi back to the ERGIC and ER depends on both the COPI-dependent pathway, which appears to be important for recyling of KDEL receptors, and a more recently described COPI-independent pathway that relies on RAB6 (reviewed in Szul and Sztul, 2011; Heffernan and Simpson, 2014). RAB6 and RAB9 also play roles at the TGN side of the Golgi, where they are implicated in the docking of vesicles derived from the endolysosomal system and the plasma membrane (reviewed in Pfeffer, 2011)
Identifier: R-HSA-2122948
Species: Homo sapiens
Compartment: plasma membrane, cytosol, nucleoplasm
Mature NOTCH1 heterodimer on the cell surface is activated by one of its ligands: DLL1 (Cordle et al. 2008, Jarriault et al. 1998), DLL4 (Benedito et al. 2009), JAG1 (Li et al. 1998, Benedito et al. 2009) or JAG2 (Luo et al. 1997, Shimizu et al. 2000), expressed in trans on a neighboring cell. Thus, a ligand-expressing cell is a signal-sending cell, while the NOTCH1 expressing cell is a signal-receiving cell. If NOTCH1 has undergone Fringe modification in the Golgi, it is preferentially activated by Delta ligands (Yang et al. 2005), DLL1 and DLL4.


Upon binding to NOTCH1 on a neighboring cell, NOTCH ligands are ubiquitinated by Mindbomb (MIB1 and MIB2) and/or Neuralized (NEURL and NEURL1B) E3 ubiquitin ligases and endocytosed (Koo et al. 2007, Koo et al. 2005, Itoh et al. 2003, Lai et al. 2001, Koutelou et al. 2008, Song et al. 2006). Endocytosis of ubiquitinated ligands is thought to mechanically stretch the bound NOTCH1 receptor, exposing a cleavage site S2 that is recognized by ADAM10 and/or ADAM17 metalloprotease (van Tetering et al. 2009, Brou et al. 2000, Hartmann et al. 2002, Pan et al. 1997). S2 cleavage of NOTCH1 produces the NEXT1 fragment which is further cleaved at an S3 cleavage site by the gamma-secretase complex, resulting in release of the NOTCH1 intracellular domain (NICD1) into the cytosol (de Strooper et al. 1999, Schroeter et al. 1998, Huppert et al. 2000). NICD1 produced by activation of NOTCH1 in response to in trans presented Delta and Jagged ligands (DLL/JAG) traffics to the nucleus where it acts as a transcription regulator.


NOTCH1 signaling can also be activated by ligands other than DLL1, DLL4, JAG1 and JAG2. CNTN1 (Contactin-1), transiently expressed during central and peripheral nervous system development, activates NOTCH1 and NOTCH2 in trans, promoting oligodendrocyte maturation and myelination (Hu et al. 2003). DNER (Delta and Notch-like epidermal growth factor-related receptor) is a transmembrane protein specifically expressed in dendrites and cell bodies of postmitotic neurons. Activation of NOTCH1 by DNER in trans may play an important role in development of the central nervous system by influencing differentiation of astrocytes (Eiraku et al. 2005). Activation of NOTCH1 by both CNTN1 and DNER is Deltex (DTX)-dependent and results in gamma-secretase mediated release of NICD1. Three members of the Deltex protein family: DTX1, DTX2 and DTX4 possess a domain involved in binding cdc10/ankyrin repeats of NOTCH. DTX proteins are considered as positive regulators of NOTCH signaling, although the exact mechanism has not been elucidated (Matsuno et al. 1998, Kishi et al. 2001).In addition, DTX can mediate downregulation of NOTCH signaling by recruiting non-visual beta-arrestins to NOTCH (Mukherjee et al. 2005), thereby trigerring NOTCH ubiquitination. DTX proteins are negatively regulated by ITCH (AIP4) ubiquitin ligase (Chastagner et al. 2006).

NOTCH1 signaling in the signal-receiving cell can be turned off in cis by expression of NOTCH ligands DLL/JAG (Cordle et al. 2008, Sprinzak et al. 2010), as well as DLK1 (Baladron et al. 2005, Bray et al. 2008). Formation of NOTCH1:ligand complexes in cis prevents interaction of NOTCH1 with ligands expressed in trans, resulting in the inhibition of NOTCH signaling. In the signal-sending cell, NOTCH signaling can be negatively regulated by the protein NUMB, which is asymmetrically distributed during cell division (Rhyu et al. 1994). NUMB recruits ITCH ubiquitin ligase to NOTCH1 and promotes sorting of NOTCH1 through late endosomes for degradation (McGill et al. 2009, Chastagner et al. 2008).
Identifier: R-HSA-1980143
Species: Homo sapiens
Compartment: plasma membrane, cytosol, nucleoplasm
NOTCH1 functions as both a transmembrane receptor presented on the cell surface and as a transcriptional regulator in the nucleus.

NOTCH1 receptor presented on the plasma membrane is activated by a membrane bound ligand expressed in trans on the surface of a neighboring cell. In trans, ligand binding triggers proteolytic cleavage of NOTCH1 and results in release of the NOTCH1 intracellular domain, NICD1, into the cytosol.

NICD1 translocates to the nucleus where it associates with RBPJ (also known as CSL or CBF) and mastermind-like (MAML) proteins (MAML1, MAML2 or MAML3; possibly also MAMLD1) to form NOTCH1 coactivator complex. NOTCH1 coactivator complex activates transcription of genes that possess RBPJ binding sites in their promoters.

Identifier: R-HSA-2979096
Species: Homo sapiens
Similar to NOTCH1, NOTCH2 is activated by Delta-like and Jagged ligands (DLL/JAG) expressed in trans on a neighboring cell (Shimizu et al. 1999, Shimizu et al. 2000, Hicks et al. 2000, Ji et al. 2004). The activation triggers cleavage of NOTCH2, first by ADAM10 at the S2 cleavage site (Gibb et al. 2010, Shimizu et al. 2000), then by gamma-secretase at the S3 cleavage site (Saxena et al. 2001, De Strooper et al. 1999), resulting in the release of the intracellular domain of NOTCH2, NICD2, into the cytosol. NICD2 subsequently traffics to the nucleus where it acts as a transcription regulator.

While DLL and JAG ligands are well established, canonical NOTCH2 ligands, there is limited evidence that NOTCH2, similar to NOTCH1, can be activated by CNTN1 (contactin 1), a protein involved in oligodendrocyte maturation (Hu et al. 2003). MDK (midkine), which plays an important role in epithelial to mesenchymal transition, can also activate NOTCH2 signaling and is able to bind to the extracellular domain of NOTCH2, but the exact mechanism of MDK-induced NOTCH2 activation has not been elucidated (Huang et al. 2008, Gungor et al. 2011).

Complex (4 results from a total of 4)

Identifier: R-HSA-480463
Species: Homo sapiens
Compartment: nucleoplasm
KLF4, PBX1, OCT4 (POU5F1), SOX2, and NANOG bind the promoter of the NANOG gene.
Identifier: R-HSA-1112611
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-2889033
Species: Homo sapiens
Compartment: nucleoplasm
Identifier: R-HSA-2889014
Species: Homo sapiens
Compartment: nucleoplasm
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