Phosphoinositide phospholipase C [Caenorhabditis elegans]
Protein Classification
List of domain hits
| Name | Accession | Description | Interval | E-value | ||||||||||
| PI-PLCc_epsilon | cd08596 | Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ... |
2585-3049 | 2.52e-133 | ||||||||||
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-epsilon isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-epsilon represents a class of mammalian PI-PLC that has an N-terminal CDC25 homology domain with a guanyl-nucleotide exchange factor (GFF) activity, a pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and two predicted RA (Ras association) domains that are implicated in the binding of small GTPases, such as Ras or Rap, from the Ras family. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There is one PI-PLC-epsilon isozyme (1). PI-PLC-epsilon is activated by G alpha(12/13), G beta gamma, and activated members of Ras and Rho small GTPases. Aside from PI-PLC-epsilon identified in mammals, its eukaryotic homologs have been classified with this family. : Pssm-ID: 176538 [Multi-domain] Cd Length: 254 Bit Score: 418.48 E-value: 2.52e-133
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| EFh_PI-PLCepsilon | cd16203 | EF-hand motif found in phosphoinositide phospholipase C epsilon 1 (PI-PLC-epsilon1); ... |
2391-2571 | 2.85e-79 | ||||||||||
EF-hand motif found in phosphoinositide phospholipase C epsilon 1 (PI-PLC-epsilon1); PI-PLC-epsilon1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1, or pancreas-enriched phospholipase C, or phospholipase C-epsilon-1 (PLC-epsilon-1), is dominant in connective tissues and brain. It has been implicated in carcinogenesis, such as in bladder and intestinal tumor, oesophageal squamous cell carcinoma, gastric adenocarcinoma, murine skin cancer, head and neck cancer. PI-PLC-epsilon1 contains an N-terminal CDC25 homology domain with a guanyl-nucleotide exchange factor (GFF) activity, a pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and at least one and perhaps two C-terminal predicted RA (Ras association) domains that are implicated in the binding of small GTPases, such as Ras or Rap, from the Ras family. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There is only one PI-PLC-epsilon isozyme. It is directly activated by G alpha(12/13), G beta gamma, and activated members of Ras and Rho small GTPases. : Pssm-ID: 320033 Cd Length: 174 Bit Score: 259.95 E-value: 2.85e-79
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| RA2_PLC-epsilon | cd01780 | Ras-associating (RA) domain 2 found in Phosphatidylinositide-specific phospholipase C (PLC) ... |
3411-3514 | 7.86e-52 | ||||||||||
Ras-associating (RA) domain 2 found in Phosphatidylinositide-specific phospholipase C (PLC)-epsilon; PLC is a signaling enzyme that hydrolyzes membrane phospholipids to generate inositol triphosphate. PLC-epsilon represents a novel forth class of PLC that has a PLC catalytic core domain, a CDC25 guanine nucleotide exchange factor domain and two RA (Ras-association) domains. RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. Although PLC RA1 and RA2 have homologous ubiquitin-like folds only RA2 can bind Ras and activate it. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and involve in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. This family corresponds to the second RA domain of PLC-epsilon. : Pssm-ID: 340478 Cd Length: 102 Bit Score: 178.29 E-value: 7.86e-52
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| RasGEF | smart00147 | Guanine nucleotide exchange factor for Ras-like small GTPases; |
1738-2009 | 1.92e-51 | ||||||||||
Guanine nucleotide exchange factor for Ras-like small GTPases; : Pssm-ID: 214539 Cd Length: 242 Bit Score: 182.83 E-value: 1.92e-51
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| PLN02952 super family | cl31960 | phosphoinositide phospholipase C |
2516-3205 | 5.29e-39 | ||||||||||
phosphoinositide phospholipase C The actual alignment was detected with superfamily member PLN02952: Pssm-ID: 178538 [Multi-domain] Cd Length: 599 Bit Score: 156.70 E-value: 5.29e-39
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| ANKYR | COG0666 | Ankyrin repeat [Signal transduction mechanisms]; |
190-338 | 4.13e-14 | ||||||||||
Ankyrin repeat [Signal transduction mechanisms]; : Pssm-ID: 440430 [Multi-domain] Cd Length: 289 Bit Score: 75.76 E-value: 4.13e-14
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| Ubl1_cv_Nsp3_N-like super family | cl28922 | first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV ... |
3245-3339 | 2.77e-11 | ||||||||||
first ubiquitin-like (Ubl) domain located at the N-terminus of coronavirus SARS-CoV non-structural protein 3 (Nsp3) and related proteins; This ubiquitin-like (Ubl) domain (Ubl1) is found at the N-terminus of coronavirus Nsp3, a large multi-functional multi-domain protein which is an essential component of the replication/transcription complex (RTC). The functions of Ubl1 in CoVs are related to single-stranded RNA (ssRNA) binding and to interacting with the nucleocapsid (N) protein. SARS-CoV Ubl1 has been shown to bind ssRNA having AUA patterns, and since the 5'-UTR of the SARS-CoV genome has a number of AUA repeats, it may bind there. In mouse hepatitis virus (MHV), this Ubl1 domain binds the cognate N protein. Adjacent to Ubl1 is a Glu-rich acidic region (also referred to as hypervariable region, HVR); Ubl1 together with HVR has been called Nsp3a. Currently, the function of HVR in CoVs is unknown. This model corresponds to one of two Ubl domains in Nsp3; the other is located N-terminal to the papain-like protease (PLpro) and is not represented by this model. The actual alignment was detected with superfamily member cd17114: Pssm-ID: 475130 Cd Length: 97 Bit Score: 62.36 E-value: 2.77e-11
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| B41 super family | cl33382 | Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ... |
1411-1588 | 1.26e-10 | ||||||||||
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in myosins, ezrin, radixin, moesin, protein tyrosine phosphatases. Plasma membrane-binding domain. These proteins play structural and regulatory roles in the assembly and stabilization of specialized plasmamembrane domains. Some PDZ domain containing proteins bind one or more of this family. Now includes JAKs. The actual alignment was detected with superfamily member smart00295: Pssm-ID: 214604 [Multi-domain] Cd Length: 201 Bit Score: 63.85 E-value: 1.26e-10
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| Name | Accession | Description | Interval | E-value | ||||||||||
| PI-PLCc_epsilon | cd08596 | Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ... |
2585-3049 | 2.52e-133 | ||||||||||
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-epsilon isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-epsilon represents a class of mammalian PI-PLC that has an N-terminal CDC25 homology domain with a guanyl-nucleotide exchange factor (GFF) activity, a pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and two predicted RA (Ras association) domains that are implicated in the binding of small GTPases, such as Ras or Rap, from the Ras family. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There is one PI-PLC-epsilon isozyme (1). PI-PLC-epsilon is activated by G alpha(12/13), G beta gamma, and activated members of Ras and Rho small GTPases. Aside from PI-PLC-epsilon identified in mammals, its eukaryotic homologs have been classified with this family. Pssm-ID: 176538 [Multi-domain] Cd Length: 254 Bit Score: 418.48 E-value: 2.52e-133
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| EFh_PI-PLCepsilon | cd16203 | EF-hand motif found in phosphoinositide phospholipase C epsilon 1 (PI-PLC-epsilon1); ... |
2391-2571 | 2.85e-79 | ||||||||||
EF-hand motif found in phosphoinositide phospholipase C epsilon 1 (PI-PLC-epsilon1); PI-PLC-epsilon1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1, or pancreas-enriched phospholipase C, or phospholipase C-epsilon-1 (PLC-epsilon-1), is dominant in connective tissues and brain. It has been implicated in carcinogenesis, such as in bladder and intestinal tumor, oesophageal squamous cell carcinoma, gastric adenocarcinoma, murine skin cancer, head and neck cancer. PI-PLC-epsilon1 contains an N-terminal CDC25 homology domain with a guanyl-nucleotide exchange factor (GFF) activity, a pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and at least one and perhaps two C-terminal predicted RA (Ras association) domains that are implicated in the binding of small GTPases, such as Ras or Rap, from the Ras family. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There is only one PI-PLC-epsilon isozyme. It is directly activated by G alpha(12/13), G beta gamma, and activated members of Ras and Rho small GTPases. Pssm-ID: 320033 Cd Length: 174 Bit Score: 259.95 E-value: 2.85e-79
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| PI-PLC-X | pfam00388 | Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ... |
2588-2724 | 1.45e-69 | ||||||||||
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to form a single structural unit. Pssm-ID: 459795 [Multi-domain] Cd Length: 142 Bit Score: 230.85 E-value: 1.45e-69
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| PLCXc | smart00148 | Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ... |
2588-2725 | 1.06e-63 | ||||||||||
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. These enzymes contain 2 regions (X and Y) which together form a TIM barrel-like structure containing the active site residues. Phospholipase C enzymes (PI-PLC) act as signal transducers that generate two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. The bacterial enzyme appears to be a homologue of the mammalian PLCs. Pssm-ID: 197543 [Multi-domain] Cd Length: 143 Bit Score: 214.07 E-value: 1.06e-63
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| RA2_PLC-epsilon | cd01780 | Ras-associating (RA) domain 2 found in Phosphatidylinositide-specific phospholipase C (PLC) ... |
3411-3514 | 7.86e-52 | ||||||||||
Ras-associating (RA) domain 2 found in Phosphatidylinositide-specific phospholipase C (PLC)-epsilon; PLC is a signaling enzyme that hydrolyzes membrane phospholipids to generate inositol triphosphate. PLC-epsilon represents a novel forth class of PLC that has a PLC catalytic core domain, a CDC25 guanine nucleotide exchange factor domain and two RA (Ras-association) domains. RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. Although PLC RA1 and RA2 have homologous ubiquitin-like folds only RA2 can bind Ras and activate it. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and involve in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. This family corresponds to the second RA domain of PLC-epsilon. Pssm-ID: 340478 Cd Length: 102 Bit Score: 178.29 E-value: 7.86e-52
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| RasGEF | smart00147 | Guanine nucleotide exchange factor for Ras-like small GTPases; |
1738-2009 | 1.92e-51 | ||||||||||
Guanine nucleotide exchange factor for Ras-like small GTPases; Pssm-ID: 214539 Cd Length: 242 Bit Score: 182.83 E-value: 1.92e-51
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| PLN02952 | PLN02952 | phosphoinositide phospholipase C |
2516-3205 | 5.29e-39 | ||||||||||
phosphoinositide phospholipase C Pssm-ID: 178538 [Multi-domain] Cd Length: 599 Bit Score: 156.70 E-value: 5.29e-39
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| C2_PLC_like | cd00275 | C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ... |
3084-3205 | 8.77e-35 | ||||||||||
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology. Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 130.74 E-value: 8.77e-35
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| RasGEF | pfam00617 | RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases. |
1745-1911 | 1.20e-20 | ||||||||||
RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases. Pssm-ID: 459872 Cd Length: 179 Bit Score: 91.88 E-value: 1.20e-20
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| RasGEF | cd00155 | Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ... |
1739-1919 | 2.06e-15 | ||||||||||
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEFs) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors. Pssm-ID: 238087 [Multi-domain] Cd Length: 237 Bit Score: 78.45 E-value: 2.06e-15
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| ANKYR | COG0666 | Ankyrin repeat [Signal transduction mechanisms]; |
190-338 | 4.13e-14 | ||||||||||
Ankyrin repeat [Signal transduction mechanisms]; Pssm-ID: 440430 [Multi-domain] Cd Length: 289 Bit Score: 75.76 E-value: 4.13e-14
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| C2 | smart00239 | Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ... |
3086-3185 | 9.96e-12 | ||||||||||
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles. Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 64.05 E-value: 9.96e-12
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| RA_PLC-epsilon | cd17114 | Ras-associating (RA) domain found in Phosphatidylinositide-specific phospholipase C (PLC) ... |
3245-3339 | 2.77e-11 | ||||||||||
Ras-associating (RA) domain found in Phosphatidylinositide-specific phospholipase C (PLC)-epsilon; PLC is a signaling enzyme that hydrolyzes membrane phospholipids to generate inositol triphosphate. PLC-epsilon represents a novel forth class of PLC that has a PLC catalytic core domain, a CDC25 guanine nucleotide exchange factor domain and two RA (Ras-association) domains. RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub). Although PLC RA1 and RA2 have homologous ubiquitin-like folds only RA2 can bind Ras and activate it. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. Pssm-ID: 340634 Cd Length: 97 Bit Score: 62.36 E-value: 2.77e-11
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| RA | smart00314 | Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ... |
3248-3340 | 3.90e-11 | ||||||||||
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Kalhammer et al. have shown that not all RA domains bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase. Predicted RA domains in PLC210 and nore1 found to bind RasGTP. Included outliers (Grb7, Grb14, adenylyl cyclases etc.) Pssm-ID: 214612 Cd Length: 90 Bit Score: 61.93 E-value: 3.90e-11
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| PLN02223 | PLN02223 | phosphoinositide phospholipase C |
2520-2703 | 4.59e-11 | ||||||||||
phosphoinositide phospholipase C Pssm-ID: 165867 [Multi-domain] Cd Length: 537 Bit Score: 68.51 E-value: 4.59e-11
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| B41 | smart00295 | Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ... |
1411-1588 | 1.26e-10 | ||||||||||
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in myosins, ezrin, radixin, moesin, protein tyrosine phosphatases. Plasma membrane-binding domain. These proteins play structural and regulatory roles in the assembly and stabilization of specialized plasmamembrane domains. Some PDZ domain containing proteins bind one or more of this family. Now includes JAKs. Pssm-ID: 214604 [Multi-domain] Cd Length: 201 Bit Score: 63.85 E-value: 1.26e-10
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| RA | smart00314 | Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ... |
3412-3514 | 2.28e-10 | ||||||||||
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Kalhammer et al. have shown that not all RA domains bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase. Predicted RA domains in PLC210 and nore1 found to bind RasGTP. Included outliers (Grb7, Grb14, adenylyl cyclases etc.) Pssm-ID: 214612 Cd Length: 90 Bit Score: 59.62 E-value: 2.28e-10
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| Ank_2 | pfam12796 | Ankyrin repeats (3 copies); |
193-328 | 1.38e-08 | ||||||||||
Ankyrin repeats (3 copies); Pssm-ID: 463710 [Multi-domain] Cd Length: 91 Bit Score: 54.74 E-value: 1.38e-08
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| PHA03100 | PHA03100 | ankyrin repeat protein; Provisional |
189-338 | 5.04e-07 | ||||||||||
ankyrin repeat protein; Provisional Pssm-ID: 222984 [Multi-domain] Cd Length: 422 Bit Score: 55.44 E-value: 5.04e-07
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| C2 | pfam00168 | C2 domain; |
3086-3179 | 2.02e-05 | ||||||||||
C2 domain; Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 46.16 E-value: 2.02e-05
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| FERM_M | pfam00373 | FERM central domain; This domain is the central structural domain of the FERM domain. |
1402-1441 | 3.81e-04 | ||||||||||
FERM central domain; This domain is the central structural domain of the FERM domain. Pssm-ID: 459788 [Multi-domain] Cd Length: 117 Bit Score: 42.64 E-value: 3.81e-04
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| RA | pfam00788 | Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ... |
3420-3516 | 1.62e-03 | ||||||||||
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase. Pssm-ID: 425871 Cd Length: 93 Bit Score: 40.39 E-value: 1.62e-03
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| EF-hand_like | pfam09279 | Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ... |
2518-2571 | 2.13e-03 | ||||||||||
Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are predominantly found in phosphoinositide-specific phospholipase C. They adopt a structure consisting of a core of four alpha helices, in an EF like fold, and are required for functioning of the enzyme. Pssm-ID: 401279 [Multi-domain] Cd Length: 85 Bit Score: 39.54 E-value: 2.13e-03
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| RA | pfam00788 | Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ... |
3263-3339 | 3.53e-03 | ||||||||||
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase. Pssm-ID: 425871 Cd Length: 93 Bit Score: 39.24 E-value: 3.53e-03
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| Name | Accession | Description | Interval | E-value | ||||||||||
| PI-PLCc_epsilon | cd08596 | Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ... |
2585-3049 | 2.52e-133 | ||||||||||
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-epsilon isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-epsilon represents a class of mammalian PI-PLC that has an N-terminal CDC25 homology domain with a guanyl-nucleotide exchange factor (GFF) activity, a pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and two predicted RA (Ras association) domains that are implicated in the binding of small GTPases, such as Ras or Rap, from the Ras family. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There is one PI-PLC-epsilon isozyme (1). PI-PLC-epsilon is activated by G alpha(12/13), G beta gamma, and activated members of Ras and Rho small GTPases. Aside from PI-PLC-epsilon identified in mammals, its eukaryotic homologs have been classified with this family. Pssm-ID: 176538 [Multi-domain] Cd Length: 254 Bit Score: 418.48 E-value: 2.52e-133
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| PI-PLCc_eukaryota | cd08558 | Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; ... |
2585-2724 | 5.85e-82 | ||||||||||
Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; This family corresponds to the catalytic domain present in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) and similar proteins. The higher eukaryotic PI-PLCs play a critical role in most signal transduction pathways, controlling numerous cellular events such as cell growth, proliferation, excitation and secretion. They strictly require Ca2+ for the catalytic activity. They display a clear preference towards the hydrolysis of the more highly phosphorylated membrane phospholipids PI-analogues, phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol-4-phosphate (PIP), to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. The eukaryotic PI-PLCs have a multidomain organization that consists of a PLC catalytic core domain, and various regulatory domains, such as the pleckstrin homology (PH) domain, EF-hand motif, and C2 domain. The catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a linker region. The catalytic mechanism of eukaryotic PI-PLCs is based on general base and acid catalysis utilizing two well conserved histidines and consists of two steps, a phosphotransfer and a phosphodiesterase reaction. The mammalian PI-PLCs consist of 13 isozymes, which are classified into six-subfamilies, PI-PLC-delta (1,3 and 4), -beta(1-4), -gamma(1,2), -epsilon, -zeta, and -eta (1,2). Ca2+ is required for the activation of all forms of mammalian PI-PLCs, and the concentration of calcium influences substrate specificity. This family also includes metazoan phospholipase C related but catalytically inactive proteins (PRIP), which belong to a group of novel inositol trisphosphate binding proteins. Due to the replacement of critical catalytic residues, PRIP does not have PLC enzymatic activity. Pssm-ID: 176501 [Multi-domain] Cd Length: 226 Bit Score: 269.71 E-value: 5.85e-82
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| EFh_PI-PLCepsilon | cd16203 | EF-hand motif found in phosphoinositide phospholipase C epsilon 1 (PI-PLC-epsilon1); ... |
2391-2571 | 2.85e-79 | ||||||||||
EF-hand motif found in phosphoinositide phospholipase C epsilon 1 (PI-PLC-epsilon1); PI-PLC-epsilon1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1, or pancreas-enriched phospholipase C, or phospholipase C-epsilon-1 (PLC-epsilon-1), is dominant in connective tissues and brain. It has been implicated in carcinogenesis, such as in bladder and intestinal tumor, oesophageal squamous cell carcinoma, gastric adenocarcinoma, murine skin cancer, head and neck cancer. PI-PLC-epsilon1 contains an N-terminal CDC25 homology domain with a guanyl-nucleotide exchange factor (GFF) activity, a pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and at least one and perhaps two C-terminal predicted RA (Ras association) domains that are implicated in the binding of small GTPases, such as Ras or Rap, from the Ras family. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There is only one PI-PLC-epsilon isozyme. It is directly activated by G alpha(12/13), G beta gamma, and activated members of Ras and Rho small GTPases. Pssm-ID: 320033 Cd Length: 174 Bit Score: 259.95 E-value: 2.85e-79
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| PI-PLCc_delta | cd08593 | Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily ... |
2586-3048 | 1.96e-78 | ||||||||||
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This CD corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Different PI-PLC-delta isozymes have different tissue distribution and different subcellular locations. PI-PLC-delta1 is mostly a cytoplasmic protein, PI-PLC-delta3 is located in the membrane, and PI-PLC-delta4 is predominantly detected in the cell nucleus. Aside from three PI-PLC-delta isozymes identified in mammals, some eukaryotic PI-PLC-delta homologs have been classified to this CD. Pssm-ID: 176535 [Multi-domain] Cd Length: 257 Bit Score: 261.12 E-value: 1.96e-78
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| PI-PLCc_beta | cd08591 | Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ... |
2585-3048 | 1.86e-74 | ||||||||||
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are four PLC-beta isozymes (1-4). They are activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. The beta-gamma subunits of heterotrimeric G proteins are known to activate the PLC-beta2 and -beta3 isozymes only. Aside from four PLC-beta isozymes identified in mammals, some eukaryotic PLC-beta homologs have been classified into this subfamily, such as NorpA and PLC-21 from Drosophila and PLC-beta from turkey, Xenopus, sponge, and hydra. Pssm-ID: 176533 [Multi-domain] Cd Length: 257 Bit Score: 249.56 E-value: 1.86e-74
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| PI-PLC-X | pfam00388 | Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ... |
2588-2724 | 1.45e-69 | ||||||||||
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to form a single structural unit. Pssm-ID: 459795 [Multi-domain] Cd Length: 142 Bit Score: 230.85 E-value: 1.45e-69
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| PI-PLC1c_yeast | cd08598 | Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This ... |
2585-2724 | 5.38e-65 | ||||||||||
Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This family corresponds to the catalytic domain present in a group of putative phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) encoded by PLC1 genes from yeasts, which are homologs of the delta isoforms of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The prototype of this CD is protein Plc1p encoded by PLC1 genes from Saccharomyces cerevisiae. Plc1p contains both highly conserved X- and Y- regions of PLC catalytic core domain, as well as a presumptive EF-hand like calcium binding motif. Experiments show that Plc1p displays calcium dependent catalytic properties with high similarity to those of the mammalian PLCs, and plays multiple roles in modulating the membrane/protein interactions in filamentation control. CaPlc1p encoded by CAPLC1 from the closely related yeast Candida albicans, an orthologue of S. cerevisiae Plc1p, is also included in this group. Like Plc1p, CaPlc1p has conserved presumptive catalytic domain, shows PLC activity when expressed in E. coli, and is involved in multiple cellular processes. There are two other gene copies of CAPLC1 in C. albicans, CAPLC2 (also named as PIPLC) and CAPLC3. Experiments show CaPlc1p is the only enzyme in C. albicans which functions as PLC. The biological functions of CAPLC2 and CAPLC3 gene products must be clearly different from CaPlc1p, but their exact roles remain unclear. Moreover, CAPLC2 and CAPLC3 gene products are more similar to extracellular bacterial PI-PLC than to the eukaryotic PI-PLC, and they are not included in this subfamily. Pssm-ID: 176540 [Multi-domain] Cd Length: 231 Bit Score: 221.35 E-value: 5.38e-65
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| PLCXc | smart00148 | Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ... |
2588-2725 | 1.06e-63 | ||||||||||
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. These enzymes contain 2 regions (X and Y) which together form a TIM barrel-like structure containing the active site residues. Phospholipase C enzymes (PI-PLC) act as signal transducers that generate two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. The bacterial enzyme appears to be a homologue of the mammalian PLCs. Pssm-ID: 197543 [Multi-domain] Cd Length: 143 Bit Score: 214.07 E-value: 1.06e-63
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| PI-PLCc_PRIP_metazoa | cd08597 | Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This ... |
2586-3049 | 1.96e-62 | ||||||||||
Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This family corresponds to the catalytic domain present in metazoan phospholipase C related, but catalytically inactive proteins (PRIP), which belong to a group of novel Inositol 1,4,5-trisphosphate (InsP3) binding protein. PRIP has a primary structure and domain architecture, incorporating a pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain with highly conserved X- and Y-regions split by a linker sequence, and a C-terminal C2 domain, similar to phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11)-delta isoforms. Due to replacement of critical catalytic residues, PRIP do not have PLC enzymatic activity. PRIP consists of two subfamilies, PRIP-1(previously known as p130 or PLC-1), which is predominantly expressed in the brain, and PRIP-2 (previously known as PLC-2), which exhibits a relatively ubiquitous expression. Experiments show both, PRIP-1 and PRIP-2, are involved in InsP3-mediated calcium signaling pathway and GABA(A)receptor-mediated signaling pathway. In addition, PRIP-2 acts as a negative regulator of B-cell receptor signaling and immune responses. Pssm-ID: 176539 [Multi-domain] Cd Length: 260 Bit Score: 215.36 E-value: 1.96e-62
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| PI-PLCc_gamma | cd08592 | Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ... |
2586-2725 | 4.58e-62 | ||||||||||
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain.The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. There are two PI-PLC-gamma isozymes (1-2). They are activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region. Aside from the two PI-PLC-gamma isozymes identified in mammals, some eukaryotic PI-PLC-gamma homologs have been classified with this subfamily. Pssm-ID: 176534 [Multi-domain] Cd Length: 229 Bit Score: 213.06 E-value: 4.58e-62
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| PI-PLCc_delta3 | cd08630 | Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily ... |
2586-3046 | 1.01e-61 | ||||||||||
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta3 isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This family corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). Unlike PI-PLC-delta 4, PI-PLC-delta1 and 3 possess a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1 and 3 from the cell nucleus. Pssm-ID: 176567 [Multi-domain] Cd Length: 258 Bit Score: 212.96 E-value: 1.01e-61
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| PI-PLCc_delta1 | cd08629 | Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily ... |
2586-3049 | 4.34e-57 | ||||||||||
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta1 isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This subfamily corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Unlike PI-PLC-delta 4, PI-PLC-delta1 and 3 possess a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1and 3 from the cell nucleus. Experiments show PI-PLC-delta1 is essential for normal hair formation. Pssm-ID: 176566 [Multi-domain] Cd Length: 258 Bit Score: 199.88 E-value: 4.34e-57
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| PI-PLCc_beta4 | cd08626 | Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily ... |
2587-3047 | 7.46e-57 | ||||||||||
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 4. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta4 is expressed in high concentrations in cerebellar Purkinje and granule cells, the median geniculate body, and the lateral geniculate nucleus. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. Pssm-ID: 176563 [Multi-domain] Cd Length: 257 Bit Score: 199.22 E-value: 7.46e-57
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| PI-PLCc_eta | cd08594 | Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family ... |
2586-2722 | 1.32e-56 | ||||||||||
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are two PI-PLC-eta isozymes (1-2), both neuron-specific enzymes. They function as calcium sensors that are activated by small increases in intracellular calcium concentrations. The PI-PLC-eta isozymes are also activated through GPCR stimulation. Aside from the PI-PLC-eta isozymes identified in mammals, their eukaryotic homologs are also present in this family. Pssm-ID: 176536 [Multi-domain] Cd Length: 227 Bit Score: 197.33 E-value: 1.32e-56
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| PI-PLCc_gamma1 | cd08627 | Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily ... |
2586-2725 | 1.14e-53 | ||||||||||
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma1, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. PI-PLC-gamma1 is ubiquitously expressed. It is activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region. Pssm-ID: 176564 [Multi-domain] Cd Length: 229 Bit Score: 188.70 E-value: 1.14e-53
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| PI-PLCc_gamma2 | cd08628 | Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily ... |
2586-3046 | 2.69e-53 | ||||||||||
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozyme 2. PI-PLC is a signaling enzyme that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma2, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. PI-PLC-gamma2 is highly expressed in cells of hematopoietic origin. It is activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region. Unlike PI-PLC-gamma1, the activation of PI-PLC-gamma2 may require concurrent stimulation of PI 3-kinase. Pssm-ID: 176565 [Multi-domain] Cd Length: 254 Bit Score: 188.73 E-value: 2.69e-53
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| PI-PLCc_eta2 | cd08633 | Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ... |
2586-2722 | 6.66e-52 | ||||||||||
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozyme 2. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-eta2 is a neuron-specific enzyme and expressed in the brain. It may in part function downstream of G-protein-coupled receptors and play an important role in the formation and maintenance of the neuronal network in the postnatal brain. Pssm-ID: 176570 [Multi-domain] Cd Length: 254 Bit Score: 184.86 E-value: 6.66e-52
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| RA2_PLC-epsilon | cd01780 | Ras-associating (RA) domain 2 found in Phosphatidylinositide-specific phospholipase C (PLC) ... |
3411-3514 | 7.86e-52 | ||||||||||
Ras-associating (RA) domain 2 found in Phosphatidylinositide-specific phospholipase C (PLC)-epsilon; PLC is a signaling enzyme that hydrolyzes membrane phospholipids to generate inositol triphosphate. PLC-epsilon represents a novel forth class of PLC that has a PLC catalytic core domain, a CDC25 guanine nucleotide exchange factor domain and two RA (Ras-association) domains. RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. Although PLC RA1 and RA2 have homologous ubiquitin-like folds only RA2 can bind Ras and activate it. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and involve in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. This family corresponds to the second RA domain of PLC-epsilon. Pssm-ID: 340478 Cd Length: 102 Bit Score: 178.29 E-value: 7.86e-52
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| PLCYc | smart00149 | Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ... |
2947-3061 | 8.74e-52 | ||||||||||
Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. These enzymes contain 2 regions (X and Y) which together form a TIM barrel-like structure containing the active site residues. Phospholipase C enzymes (PI-PLC) act as signal transducers that generate two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. The bacterial enzyme appears to be a homologue of the mammalian PLCs. Pssm-ID: 128454 [Multi-domain] Cd Length: 115 Bit Score: 178.59 E-value: 8.74e-52
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| PI-PLCc_eta1 | cd08632 | Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily ... |
2586-2722 | 1.56e-51 | ||||||||||
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-eta1 is a neuron-specific enzyme and expressed in only nerve tissues such as the brain and spinal cord. It may perform a fundamental role in the brain. Pssm-ID: 176569 [Multi-domain] Cd Length: 253 Bit Score: 183.69 E-value: 1.56e-51
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| RasGEF | smart00147 | Guanine nucleotide exchange factor for Ras-like small GTPases; |
1738-2009 | 1.92e-51 | ||||||||||
Guanine nucleotide exchange factor for Ras-like small GTPases; Pssm-ID: 214539 Cd Length: 242 Bit Score: 182.83 E-value: 1.92e-51
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| PI-PLCc_delta4 | cd08631 | Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily ... |
2586-3049 | 2.01e-51 | ||||||||||
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-delta4 isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-delta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C-terminal C2 domain. This CD corresponds to the catalytic domain which is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1,3 and 4). Unlike PI-PLC-delta 1 and 3, a putative nuclear export sequence (NES) located in the EF-hand domain, which may be responsible transporting PI-PLC-delta1 and 3 from the cell nucleus, is not present in PI-PLC-delta4. Experiments show PI-PLC-delta4 is required for the acrosome reaction in fertilization. Pssm-ID: 176568 [Multi-domain] Cd Length: 258 Bit Score: 183.61 E-value: 2.01e-51
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| PI-PLCc_zeta | cd08595 | Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family ... |
2586-3046 | 4.99e-51 | ||||||||||
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family corresponds to the catalytic domain presenting in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-zeta isozyme. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-zeta represents a class of sperm-specific PI-PLC that has an N-terminal EF-hand domain, a PLC catalytic core domain, and a C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There is one PLC-zeta isozyme (1). PLC-zeta plays a fundamental role in vertebrate fertilization by initiating intracellular calcium oscillations that trigger the embryo development. However, the mechanism of its activation still remains unclear. Aside from PI-PLC-zeta identified in mammals, its eukaryotic homologs have been classified with this family. Pssm-ID: 176537 [Multi-domain] Cd Length: 257 Bit Score: 182.44 E-value: 4.99e-51
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| PI-PLCc_beta2 | cd08624 | Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily ... |
2586-3047 | 2.13e-48 | ||||||||||
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 2. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta2 is expressed at highest levels in cells of hematopoietic origin. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It is also activated by the beta-gamma subunits of heterotrimeric G proteins. Pssm-ID: 176561 [Multi-domain] Cd Length: 261 Bit Score: 174.86 E-value: 2.13e-48
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| PI-PLCc_beta3 | cd08625 | Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily ... |
2586-3047 | 4.58e-46 | ||||||||||
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 3. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta3 is widely expressed at highest levels in brain, liver, and parotid gland. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It is also activated by the beta-gamma subunits of heterotrimeric G proteins. Pssm-ID: 176562 [Multi-domain] Cd Length: 258 Bit Score: 167.92 E-value: 4.58e-46
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| PI-PLCc_beta1 | cd08623 | Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily ... |
2586-2725 | 1.39e-43 | ||||||||||
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-beta1 is expressed at highest levels in specific regions of the brain. It is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. Pssm-ID: 176560 [Multi-domain] Cd Length: 258 Bit Score: 161.02 E-value: 1.39e-43
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| PI-PLC-Y | pfam00387 | Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to ... |
2886-3060 | 3.69e-40 | ||||||||||
Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to form a single structural unit. Pssm-ID: 459794 Cd Length: 114 Bit Score: 145.30 E-value: 3.69e-40
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| PI-PLCc_plant | cd08599 | Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family ... |
2585-2703 | 1.39e-39 | ||||||||||
Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family corresponds to the catalytic domain present in a group of phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11) encoded by PLC genes from higher plants, which are homologs of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The domain arrangement of plant PI-PLCs is structurally similar to the mammalian PLC-zeta isoform, which lacks the N-terminal pleckstrin homology (PH) domain, but contains EF-hand like motifs (which are absent in a few plant PLCs), a PLC catalytic core domain with X- and Y- highly conserved regions split by a linker sequence, and a C2 domain. However, at the sequence level, the plant PI-PLCs are closely related to the mammalian PLC-delta isoform. Experiments show that plant PLCs display calcium dependent PLC catalytic properties, although they lack some of the N-terminal motifs found in their mammalian counterparts. A putative calcium binding site may be located at the region spanning the X- and Y- domains. Pssm-ID: 176541 [Multi-domain] Cd Length: 228 Bit Score: 148.29 E-value: 1.39e-39
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| PLN02952 | PLN02952 | phosphoinositide phospholipase C |
2516-3205 | 5.29e-39 | ||||||||||
phosphoinositide phospholipase C Pssm-ID: 178538 [Multi-domain] Cd Length: 599 Bit Score: 156.70 E-value: 5.29e-39
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| PLN02222 | PLN02222 | phosphoinositide phospholipase C 2 |
2517-3204 | 7.09e-38 | ||||||||||
phosphoinositide phospholipase C 2 Pssm-ID: 177868 [Multi-domain] Cd Length: 581 Bit Score: 152.88 E-value: 7.09e-38
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| C2_PLC_like | cd00275 | C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ... |
3084-3205 | 8.77e-35 | ||||||||||
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology. Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 130.74 E-value: 8.77e-35
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| PLN02228 | PLN02228 | Phosphoinositide phospholipase C |
2517-3185 | 2.77e-34 | ||||||||||
Phosphoinositide phospholipase C Pssm-ID: 177873 [Multi-domain] Cd Length: 567 Bit Score: 141.71 E-value: 2.77e-34
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| PI-PLCc | cd00137 | Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This ... |
2587-2705 | 3.68e-34 | ||||||||||
Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This subfamily corresponds to the catalytic domain present in prokaryotic and eukaryotic phosphoinositide-specific phospholipase C (PI-PLC), which is a ubiquitous enzyme catalyzing the cleavage of the sn3-phosphodiester bond in the membrane phosphoinositides (phosphatidylinositol, PI; Phosphatidylinositol-4-phosphate, PIP; phosphatidylinositol 4,5-bisphosphate, PIP2) to yield inositol phosphates (inositol monosphosphate, InsP; inositol diphosphate, InsP2; inositol trisphosphate, InsP3) and diacylglycerol (DAG). The higher eukaryotic PI-PLCs (EC 3.1.4.11) have a multidomain organization that consists of a PLC catalytic core domain, and various regulatory domains. They play a critical role in most signal transduction pathways, controlling numerous cellular events, such as cell growth, proliferation, excitation and secretion. These PI-PLCs strictly require Ca2+ for their catalytic activity. They display a clear preference towards the hydrolysis of the more highly phosphorylated PI-analogues, PIP2 and PIP, to generate two important second messengers, InsP3 and DAG. InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. In contrast, bacterial PI-PLCs contain a single catalytic domain. Although their precise physiological function remains unclear, bacterial PI-PLCs may function as virulence factors in some pathogenic bacteria. They participate in Ca2+-independent PI metabolism. They are characterized as phosphatidylinositol-specific phospholipase C (EC 4.6.1.13) that selectively hydrolyze PI, not PIP or PIP2. The TIM-barrel type catalytic domain in bacterial PI-PLCs is very similar to the one in eukaryotic PI-PLCs, in which the catalytic domain is assembled from two highly conserved X- and Y-regions split by a divergent linker sequence. The catalytic mechanism of both prokaryotic and eukaryotic PI-PLCs is based on general base and acid catalysis utilizing two well conserved histidines, and consists of two steps, a phosphotransfer and a phosphodiesterase reaction. This superfamily also includes a distinctly different type of eukaryotic PLC, glycosylphosphatidylinositol-specific phospholipase C (GPI-PLC), an integral membrane protein characterized in the protozoan parasite Trypanosoma brucei. T. brucei GPI-PLC hydrolyzes the GPI-anchor on the variant specific glycoprotein (VSG), releasing dimyristyl glycerol (DMG), which may facilitate the evasion of the protozoan to the host#s immune system. It does not require Ca2+ for its activity and is more closely related to bacterial PI-PLCs, but not mammalian PI-PLCs. Pssm-ID: 176497 [Multi-domain] Cd Length: 274 Bit Score: 134.31 E-value: 3.68e-34
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| PLN02230 | PLN02230 | phosphoinositide phospholipase C 4 |
2550-3204 | 1.92e-33 | ||||||||||
phosphoinositide phospholipase C 4 Pssm-ID: 177875 [Multi-domain] Cd Length: 598 Bit Score: 139.84 E-value: 1.92e-33
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| PI-PLCc_eukaryota | cd08558 | Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; ... |
2971-3049 | 1.54e-32 | ||||||||||
Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; This family corresponds to the catalytic domain present in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) and similar proteins. The higher eukaryotic PI-PLCs play a critical role in most signal transduction pathways, controlling numerous cellular events such as cell growth, proliferation, excitation and secretion. They strictly require Ca2+ for the catalytic activity. They display a clear preference towards the hydrolysis of the more highly phosphorylated membrane phospholipids PI-analogues, phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol-4-phosphate (PIP), to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. The eukaryotic PI-PLCs have a multidomain organization that consists of a PLC catalytic core domain, and various regulatory domains, such as the pleckstrin homology (PH) domain, EF-hand motif, and C2 domain. The catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a linker region. The catalytic mechanism of eukaryotic PI-PLCs is based on general base and acid catalysis utilizing two well conserved histidines and consists of two steps, a phosphotransfer and a phosphodiesterase reaction. The mammalian PI-PLCs consist of 13 isozymes, which are classified into six-subfamilies, PI-PLC-delta (1,3 and 4), -beta(1-4), -gamma(1,2), -epsilon, -zeta, and -eta (1,2). Ca2+ is required for the activation of all forms of mammalian PI-PLCs, and the concentration of calcium influences substrate specificity. This family also includes metazoan phospholipase C related but catalytically inactive proteins (PRIP), which belong to a group of novel inositol trisphosphate binding proteins. Due to the replacement of critical catalytic residues, PRIP does not have PLC enzymatic activity. Pssm-ID: 176501 [Multi-domain] Cd Length: 226 Bit Score: 127.95 E-value: 1.54e-32
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| PI-PLC1c_yeast | cd08598 | Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This ... |
2975-3049 | 9.63e-24 | ||||||||||
Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This family corresponds to the catalytic domain present in a group of putative phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) encoded by PLC1 genes from yeasts, which are homologs of the delta isoforms of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The prototype of this CD is protein Plc1p encoded by PLC1 genes from Saccharomyces cerevisiae. Plc1p contains both highly conserved X- and Y- regions of PLC catalytic core domain, as well as a presumptive EF-hand like calcium binding motif. Experiments show that Plc1p displays calcium dependent catalytic properties with high similarity to those of the mammalian PLCs, and plays multiple roles in modulating the membrane/protein interactions in filamentation control. CaPlc1p encoded by CAPLC1 from the closely related yeast Candida albicans, an orthologue of S. cerevisiae Plc1p, is also included in this group. Like Plc1p, CaPlc1p has conserved presumptive catalytic domain, shows PLC activity when expressed in E. coli, and is involved in multiple cellular processes. There are two other gene copies of CAPLC1 in C. albicans, CAPLC2 (also named as PIPLC) and CAPLC3. Experiments show CaPlc1p is the only enzyme in C. albicans which functions as PLC. The biological functions of CAPLC2 and CAPLC3 gene products must be clearly different from CaPlc1p, but their exact roles remain unclear. Moreover, CAPLC2 and CAPLC3 gene products are more similar to extracellular bacterial PI-PLC than to the eukaryotic PI-PLC, and they are not included in this subfamily. Pssm-ID: 176540 [Multi-domain] Cd Length: 231 Bit Score: 102.71 E-value: 9.63e-24
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| RasGEF | pfam00617 | RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases. |
1745-1911 | 1.20e-20 | ||||||||||
RasGEF domain; Guanine nucleotide exchange factor for Ras-like small GTPases. Pssm-ID: 459872 Cd Length: 179 Bit Score: 91.88 E-value: 1.20e-20
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| PI-PLCc_gamma | cd08592 | Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ... |
2970-3048 | 2.10e-16 | ||||||||||
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain.The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. There are two PI-PLC-gamma isozymes (1-2). They are activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region. Aside from the two PI-PLC-gamma isozymes identified in mammals, some eukaryotic PI-PLC-gamma homologs have been classified with this subfamily. Pssm-ID: 176534 [Multi-domain] Cd Length: 229 Bit Score: 81.32 E-value: 2.10e-16
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| PI-PLCc_GDPD_SF | cd08555 | Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases ... |
2598-2709 | 3.80e-16 | ||||||||||
Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases superfamily; The PI-PLC-like phosphodiesterases superfamily represents the catalytic domains of bacterial phosphatidylinositol-specific phospholipase C (PI-PLC, EC 4.6.1.13), eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11), glycerophosphodiester phosphodiesterases (GP-GDE, EC 3.1.4.46), sphingomyelinases D (SMases D) (sphingomyelin phosphodiesterase D, EC 3.1.4.41) from spider venom, SMases D-like proteins, and phospholipase D (PLD) from several pathogenic bacteria, as well as their uncharacterized homologs found in organisms ranging from bacteria and archaea to metazoans, plants, and fungi. PI-PLCs are ubiquitous enzymes hydrolyzing the membrane lipid phosphoinositides to yield two important second messengers, inositol phosphates and diacylglycerol (DAG). GP-GDEs play essential roles in glycerol metabolism and catalyze the hydrolysis of glycerophosphodiesters to sn-glycerol-3-phosphate (G3P) and the corresponding alcohols that are major sources of carbon and phosphate. Both, PI-PLCs and GP-GDEs, can hydrolyze the 3'-5' phosphodiester bonds in different substrates, and utilize a similar mechanism of general base and acid catalysis with conserved histidine residues, which consists of two steps, a phosphotransfer and a phosphodiesterase reaction. This superfamily also includes Neurospora crassa ankyrin repeat protein NUC-2 and its Saccharomyces cerevisiae counterpart, Phosphate system positive regulatory protein PHO81, glycerophosphodiester phosphodiesterase (GP-GDE)-like protein SHV3 and SHV3-like proteins (SVLs). The residues essential for enzyme activities and metal binding are not conserved in these sequence homologs, which might suggest that the function of catalytic domains in these proteins might be distinct from those in typical PLC-like phosphodiesterases. Pssm-ID: 176498 [Multi-domain] Cd Length: 179 Bit Score: 79.02 E-value: 3.80e-16
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| RasGEF | cd00155 | Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of ... |
1739-1919 | 2.06e-15 | ||||||||||
Guanine nucleotide exchange factor for Ras-like small GTPases. Small GTP-binding proteins of the Ras superfamily function as molecular switches in fundamental events such as signal transduction, cytoskeleton dynamics and intracellular trafficking. Guanine-nucleotide-exchange factors (GEFs) positively regulate these GTP-binding proteins in response to a variety of signals. GEFs catalyze the dissociation of GDP from the inactive GTP-binding proteins. GTP can then bind and induce structural changes that allow interaction with effectors. Pssm-ID: 238087 [Multi-domain] Cd Length: 237 Bit Score: 78.45 E-value: 2.06e-15
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| PI-PLCc_eta | cd08594 | Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family ... |
2971-3046 | 2.35e-14 | ||||||||||
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-eta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-eta represents a class of neuron-speific PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal tail that terminates with a PDZ-binding motif, a potential interaction site for other signaling proteins. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are two PI-PLC-eta isozymes (1-2), both neuron-specific enzymes. They function as calcium sensors that are activated by small increases in intracellular calcium concentrations. The PI-PLC-eta isozymes are also activated through GPCR stimulation. Aside from the PI-PLC-eta isozymes identified in mammals, their eukaryotic homologs are also present in this family. Pssm-ID: 176536 [Multi-domain] Cd Length: 227 Bit Score: 75.22 E-value: 2.35e-14
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| PI-PLCc_plant | cd08599 | Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family ... |
2975-3046 | 2.71e-14 | ||||||||||
Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family corresponds to the catalytic domain present in a group of phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11) encoded by PLC genes from higher plants, which are homologs of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The domain arrangement of plant PI-PLCs is structurally similar to the mammalian PLC-zeta isoform, which lacks the N-terminal pleckstrin homology (PH) domain, but contains EF-hand like motifs (which are absent in a few plant PLCs), a PLC catalytic core domain with X- and Y- highly conserved regions split by a linker sequence, and a C2 domain. However, at the sequence level, the plant PI-PLCs are closely related to the mammalian PLC-delta isoform. Experiments show that plant PLCs display calcium dependent PLC catalytic properties, although they lack some of the N-terminal motifs found in their mammalian counterparts. A putative calcium binding site may be located at the region spanning the X- and Y- domains. Pssm-ID: 176541 [Multi-domain] Cd Length: 228 Bit Score: 75.10 E-value: 2.71e-14
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| PI-PLCc_gamma1 | cd08627 | Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily ... |
2973-3046 | 3.20e-14 | ||||||||||
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-gamma isozyme 1. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-gamma represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, and a C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma1, a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region is present within this linker region. PI-PLC-gamma1 is ubiquitously expressed. It is activated by receptor and non-receptor tyrosine kinases due to the presence of two SH2 and a single SH3 domain within the linker region. Pssm-ID: 176564 [Multi-domain] Cd Length: 229 Bit Score: 75.06 E-value: 3.20e-14
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| ANKYR | COG0666 | Ankyrin repeat [Signal transduction mechanisms]; |
190-338 | 4.13e-14 | ||||||||||
Ankyrin repeat [Signal transduction mechanisms]; Pssm-ID: 440430 [Multi-domain] Cd Length: 289 Bit Score: 75.76 E-value: 4.13e-14
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| RA_PLC-epsilon | cd17114 | Ras-associating (RA) domain found in Phosphatidylinositide-specific phospholipase C (PLC) ... |
3413-3511 | 1.48e-13 | ||||||||||
Ras-associating (RA) domain found in Phosphatidylinositide-specific phospholipase C (PLC)-epsilon; PLC is a signaling enzyme that hydrolyzes membrane phospholipids to generate inositol triphosphate. PLC-epsilon represents a novel forth class of PLC that has a PLC catalytic core domain, a CDC25 guanine nucleotide exchange factor domain and two RA (Ras-association) domains. RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub). Although PLC RA1 and RA2 have homologous ubiquitin-like folds only RA2 can bind Ras and activate it. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. Pssm-ID: 340634 Cd Length: 97 Bit Score: 68.91 E-value: 1.48e-13
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| ANKYR | COG0666 | Ankyrin repeat [Signal transduction mechanisms]; |
193-338 | 1.77e-13 | ||||||||||
Ankyrin repeat [Signal transduction mechanisms]; Pssm-ID: 440430 [Multi-domain] Cd Length: 289 Bit Score: 74.22 E-value: 1.77e-13
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| C2 | smart00239 | Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ... |
3086-3185 | 9.96e-12 | ||||||||||
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles. Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 64.05 E-value: 9.96e-12
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| RA_PLC-epsilon | cd17114 | Ras-associating (RA) domain found in Phosphatidylinositide-specific phospholipase C (PLC) ... |
3245-3339 | 2.77e-11 | ||||||||||
Ras-associating (RA) domain found in Phosphatidylinositide-specific phospholipase C (PLC)-epsilon; PLC is a signaling enzyme that hydrolyzes membrane phospholipids to generate inositol triphosphate. PLC-epsilon represents a novel forth class of PLC that has a PLC catalytic core domain, a CDC25 guanine nucleotide exchange factor domain and two RA (Ras-association) domains. RA domain has the beta-grasp ubiquitin-like (Ubl) fold with low sequence similarity to ubiquitin (Ub). Although PLC RA1 and RA2 have homologous ubiquitin-like folds only RA2 can bind Ras and activate it. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and are involved in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. Pssm-ID: 340634 Cd Length: 97 Bit Score: 62.36 E-value: 2.77e-11
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| RA | smart00314 | Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ... |
3248-3340 | 3.90e-11 | ||||||||||
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Kalhammer et al. have shown that not all RA domains bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase. Predicted RA domains in PLC210 and nore1 found to bind RasGTP. Included outliers (Grb7, Grb14, adenylyl cyclases etc.) Pssm-ID: 214612 Cd Length: 90 Bit Score: 61.93 E-value: 3.90e-11
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| PLN02223 | PLN02223 | phosphoinositide phospholipase C |
2520-2703 | 4.59e-11 | ||||||||||
phosphoinositide phospholipase C Pssm-ID: 165867 [Multi-domain] Cd Length: 537 Bit Score: 68.51 E-value: 4.59e-11
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| B41 | smart00295 | Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in ... |
1411-1588 | 1.26e-10 | ||||||||||
Band 4.1 homologues; Also known as ezrin/radixin/moesin (ERM) protein domains. Present in myosins, ezrin, radixin, moesin, protein tyrosine phosphatases. Plasma membrane-binding domain. These proteins play structural and regulatory roles in the assembly and stabilization of specialized plasmamembrane domains. Some PDZ domain containing proteins bind one or more of this family. Now includes JAKs. Pssm-ID: 214604 [Multi-domain] Cd Length: 201 Bit Score: 63.85 E-value: 1.26e-10
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| RA | smart00314 | Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ... |
3412-3514 | 2.28e-10 | ||||||||||
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Kalhammer et al. have shown that not all RA domains bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase. Predicted RA domains in PLC210 and nore1 found to bind RasGTP. Included outliers (Grb7, Grb14, adenylyl cyclases etc.) Pssm-ID: 214612 Cd Length: 90 Bit Score: 59.62 E-value: 2.28e-10
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| PLN02223 | PLN02223 | phosphoinositide phospholipase C |
2993-3205 | 8.58e-10 | ||||||||||
phosphoinositide phospholipase C Pssm-ID: 165867 [Multi-domain] Cd Length: 537 Bit Score: 64.66 E-value: 8.58e-10
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| Ank_2 | pfam12796 | Ankyrin repeats (3 copies); |
193-328 | 1.38e-08 | ||||||||||
Ankyrin repeats (3 copies); Pssm-ID: 463710 [Multi-domain] Cd Length: 91 Bit Score: 54.74 E-value: 1.38e-08
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| ANKYR | COG0666 | Ankyrin repeat [Signal transduction mechanisms]; |
263-338 | 3.52e-08 | ||||||||||
Ankyrin repeat [Signal transduction mechanisms]; Pssm-ID: 440430 [Multi-domain] Cd Length: 289 Bit Score: 58.04 E-value: 3.52e-08
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| EFh_PI-PLCbeta | cd16200 | EF-hand motif found in metazoan phosphoinositide-specific phospholipase C (PI-PLC)-beta ... |
2518-2571 | 1.38e-07 | ||||||||||
EF-hand motif found in metazoan phosphoinositide-specific phospholipase C (PI-PLC)-beta isozymes; PI-PLC-beta isozymes represent a class of metazoan PI-PLCs that hydrolyze the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) to propagate diverse intracellular responses that underlie the physiological action of many hormones, neurotransmitters, and growth factors (EC 3.1.4.11). They have been implicated in numerous processes relevant to central nervous system (CNS), including chemotaxis, cardiovascular function, neuronal signaling, and opioid sensitivity. Like other PI-PLC isozymes, PI-PLC-beta isozymes contain a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. Besides, they have a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are four PI-PLC-beta isozymes (1-4). PI-PLC-beta1 and PI-PLC-beta3 are expressed in a wide range of tissues and cell types, whereas PI-PLC-beta2 and PI-PLC-beta4 have been found only in hematopoietic and neuronal tissues, respectively. All PI-PLC-beta isozymes are activated by the heterotrimeric G protein alpha subunits of the Gq class through their C2 domain and long C-terminal extension. They are GTPase-activating proteins (GAPs) for these G alpha(q) proteins. PI-PLC-beta2 and PI-PLC-beta3 can also be activated by beta-gamma subunits of the G alpha(i/o) family of heterotrimeric G proteins and the small GTPases such as Rac and Cdc42. This family also includes two invertebrate homologs of PI-PLC-beta, PLC21 from cephalopod retina and No receptor potential A protein (NorpA) from Drosophila melanogaster. Pssm-ID: 320030 [Multi-domain] Cd Length: 153 Bit Score: 53.79 E-value: 1.38e-07
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| PHA03100 | PHA03100 | ankyrin repeat protein; Provisional |
189-338 | 5.04e-07 | ||||||||||
ankyrin repeat protein; Provisional Pssm-ID: 222984 [Multi-domain] Cd Length: 422 Bit Score: 55.44 E-value: 5.04e-07
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| EFh_PI-PLCdelta | cd16202 | EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta ... |
2518-2571 | 1.68e-06 | ||||||||||
EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta isozymes represent a class of metazoan PI-PLCs that are some of the most sensitive to calcium among all PLCs. Their activation is modulated by intracellular calcium ion concentration, phospholipids, polyamines, and other proteins, such as RhoAGAP. Like other PI-PLC isozymes, PI-PLC-delta isozymes contain a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are three PI-PLC-delta isozymes (1, 3 and 4). PI-PLC-delta1 is relatively well characterized. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. Different PI-PLC-delta isozymes have different tissue distribution and different subcellular locations. PI-PLC-delta1 is mostly a cytoplasmic protein, PI-PLC-delta3 is located in the membrane, and PI-PLC-delta4 is predominantly detected in the cell nucleus. PI-PLC-delta isozymes is evolutionarily conserved even in non-mammalian species, such as yeast, slime molds and plants. Pssm-ID: 320032 [Multi-domain] Cd Length: 140 Bit Score: 50.30 E-value: 1.68e-06
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| C2 | pfam00168 | C2 domain; |
3086-3179 | 2.02e-05 | ||||||||||
C2 domain; Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 46.16 E-value: 2.02e-05
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| EFh_PI-PLC | cd15898 | EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ... |
2516-2571 | 4.61e-05 | ||||||||||
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) isozymes; PI-PLC isozymes are signaling enzymes that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. This family corresponds to the four EF-hand motifs containing PI-PLC isozymes, including PI-PLC-beta (1-4), -gamma (1-2), -delta (1,3,4), -epsilon (1), -zeta (1), eta (1-2). Lower eukaryotes such as yeast and slime molds contain only delta-type isozymes. In contrast, other types of isoforms present in higher eukaryotes. This family also includes 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1 (PLC1) from fungi. Some homologs from plants contain only two atypical EF-hand motifs and they are not included. All PI-PLC isozymes except sperm-specific PI-PLC-zeta share a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. PI-PLC-zeta lacks the PH domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Most of EF-hand motifs found in PI-PLCs consist of a helix-loop-helix structure, but lack residues critical to metal binding. Moreover, the EF-hand region of most of PI-PLCs may have an important regulatory function, but it has yet to be identified. However, PI-PLC-zeta is a key exception. It is responsible for Ca2+ oscillations in fertilized oocytes and exhibits a high sensitivity to Ca2+ mediated through its EF-hand domain. In addition, PI-PLC-eta2 shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Also it appears that PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. PI-PLCs can be activated by a variety of extracellular ligands, such as growth factors, hormones, cytokines and lipids. Their activation has been implicated in tumorigenesis and/or metastasis linked to migration, proliferation, growth, inflammation, angiogenesis and actin cytoskeleton reorganization. PI-PLC-beta isozymes are activated by G-protein coupled receptor (GPCR) through different mechanisms. However, PI-PLC-gamma isozymes are activated by receptor tyrosine kinase (RTK), such as Rho and Ras GTPases. In contrast, PI-PLC-epsilon are activated by both GPCR and RTK. PI-PLC-delta1 and PLC-eta 1 are activated by GPCR-mediated calcium mobilization. The activation mechanism for PI-PLC-zeta remains unclear. Pssm-ID: 320029 [Multi-domain] Cd Length: 137 Bit Score: 45.74 E-value: 4.61e-05
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| PHA02878 | PHA02878 | ankyrin repeat protein; Provisional |
193-306 | 5.20e-05 | ||||||||||
ankyrin repeat protein; Provisional Pssm-ID: 222939 [Multi-domain] Cd Length: 477 Bit Score: 49.11 E-value: 5.20e-05
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| Ank_2 | pfam12796 | Ankyrin repeats (3 copies); |
267-358 | 9.04e-05 | ||||||||||
Ankyrin repeats (3 copies); Pssm-ID: 463710 [Multi-domain] Cd Length: 91 Bit Score: 43.95 E-value: 9.04e-05
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| PHA02874 | PHA02874 | ankyrin repeat protein; Provisional |
191-340 | 1.05e-04 | ||||||||||
ankyrin repeat protein; Provisional Pssm-ID: 165205 [Multi-domain] Cd Length: 434 Bit Score: 48.04 E-value: 1.05e-04
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| EFh_PRIP1 | cd16222 | EF-hand motif found in phospholipase C-related but catalytically inactive protein 1 (PRIP-1); ... |
2518-2571 | 1.74e-04 | ||||||||||
EF-hand motif found in phospholipase C-related but catalytically inactive protein 1 (PRIP-1); PRIP-1, also termed phospholipase C-deleted in lung carcinoma, or inactive phospholipase C-like protein 1 (PLC-L1), or p130, is a novel inositol 1,4,5-trisphosphate (InsP3) binding protein that is predominantly expressed in the brain. It is involved in InsP3-mediated calcium signaling pathway and GABA(A)receptor-mediated signaling pathway. It interacts with the catalytic subunits of protein phosphatase 1 (PP1) and protein phosphatase 2A (PP2A), and functions as a scaffold to regulate the activities and subcellular localizations of both PP1 and PP2A in phospho-dependent cellular signaling. It also promotes the translocation of phosphatases to lipid droplets to trigger the dephosphorylation of hormone-sensitive lipase (HSL) and perilipin A, thus reducing protein kinase A (PKA)-mediated lipolysis. Moreover, PRIP-1 plays an important role in insulin granule exocytosis through the association with GABAA-receptor-associated protein (GABARAP) to form a complex to regulate KIF5B-mediated insulin secretion. It also inhibits regulated exocytosis through direct interactions with syntaxin 1 and synaptosomal-associated protein 25 (SNAP-25) via its C2 domain. Furthermore, PRIP-1 has been implicated in the negative regulation of bone formation. PRIP-1 has a primary structure and domain architecture, incorporating a pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain with highly conserved X- and Y-regions split by a linker sequence, and a C-terminal C2 domain, similar to phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11)-delta isoforms. Due to replacement of critical catalytic residues, PRIP-1 does not have PLC enzymatic activity. Pssm-ID: 320052 [Multi-domain] Cd Length: 143 Bit Score: 44.47 E-value: 1.74e-04
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| C2 | cd00030 | C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ... |
3087-3164 | 2.93e-04 | ||||||||||
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Pssm-ID: 175973 [Multi-domain] Cd Length: 102 Bit Score: 42.82 E-value: 2.93e-04
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| FERM_M | pfam00373 | FERM central domain; This domain is the central structural domain of the FERM domain. |
1402-1441 | 3.81e-04 | ||||||||||
FERM central domain; This domain is the central structural domain of the FERM domain. Pssm-ID: 459788 [Multi-domain] Cd Length: 117 Bit Score: 42.64 E-value: 3.81e-04
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| EFh_PI-PLCzeta | cd16204 | EF-hand motif found in phosphoinositide phospholipase C zeta 1 (PI-PLC-zeta1); PI-PLC-zeta1, ... |
2523-2568 | 1.34e-03 | ||||||||||
EF-hand motif found in phosphoinositide phospholipase C zeta 1 (PI-PLC-zeta1); PI-PLC-zeta1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase zeta-1, or phospholipase C-zeta-1 (PLC-zeta-1), or testis-development protein NYD-SP27, is only found in the testis. The sperm-specific PI-PLC plays a fundamental role in vertebrate fertilization by initiating intracellular calcium oscillations that trigger the embryo development. However, the mechanism of its activation still remains unclear. PI-PLC-zeta1 contains an N-terminal four atypical EF-hand motifs, a PLC catalytic core domain, and a C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unlike other PI-PLCs, PI-PLC-zeta is responsible for Ca2+ oscillations in fertilized oocytes and exhibits a high sensitivity to Ca2+ mediated through its EF-hand domain. There is only one PLC-zeta isozyme. Aside from PI-PLC-zeta identified in mammals, its eukaryotic homologs have been classified with this family. Pssm-ID: 320034 [Multi-domain] Cd Length: 142 Bit Score: 41.72 E-value: 1.34e-03
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| RA2_PLC-epsilon | cd01780 | Ras-associating (RA) domain 2 found in Phosphatidylinositide-specific phospholipase C (PLC) ... |
3270-3339 | 1.54e-03 | ||||||||||
Ras-associating (RA) domain 2 found in Phosphatidylinositide-specific phospholipase C (PLC)-epsilon; PLC is a signaling enzyme that hydrolyzes membrane phospholipids to generate inositol triphosphate. PLC-epsilon represents a novel forth class of PLC that has a PLC catalytic core domain, a CDC25 guanine nucleotide exchange factor domain and two RA (Ras-association) domains. RA domain has the beta-grasp ubiquitin-like fold with low sequence similarity to ubiquitin. Although PLC RA1 and RA2 have homologous ubiquitin-like folds only RA2 can bind Ras and activate it. RA domain-containing proteins function by interacting with Ras proteins directly or indirectly and involve in several different functions ranging from tumor suppression to being oncoproteins. Ras proteins are small GTPases that are involved in cellular signal transduction. This family corresponds to the second RA domain of PLC-epsilon. Pssm-ID: 340478 Cd Length: 102 Bit Score: 40.77 E-value: 1.54e-03
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| RA | pfam00788 | Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ... |
3420-3516 | 1.62e-03 | ||||||||||
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase. Pssm-ID: 425871 Cd Length: 93 Bit Score: 40.39 E-value: 1.62e-03
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| EF-hand_like | pfam09279 | Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ... |
2518-2571 | 2.13e-03 | ||||||||||
Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are predominantly found in phosphoinositide-specific phospholipase C. They adopt a structure consisting of a core of four alpha helices, in an EF like fold, and are required for functioning of the enzyme. Pssm-ID: 401279 [Multi-domain] Cd Length: 85 Bit Score: 39.54 E-value: 2.13e-03
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| EFh_PRIP | cd16206 | EF-hand motif found in phospholipase C-related but catalytically inactive proteins (PRIP); ... |
2518-2568 | 3.39e-03 | ||||||||||
EF-hand motif found in phospholipase C-related but catalytically inactive proteins (PRIP); This family represents a class of metazoan phospholipase C related, but catalytically inactive proteins (PRIP), which belong to a group of novel inositol 1,4,5-trisphosphate (InsP3) binding protein. PRIP has a primary structure and domain architecture, incorporating a pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain with highly conserved X- and Y-regions split by a linker sequence, and a C-terminal C2 domain, similar to phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11)-delta isoforms. Due to replacement of critical catalytic residues, PRIP do not have PLC enzymatic activity. PRIP consists of two subfamilies, PRIP-1(also known as p130 or PLC-L1), which is predominantly expressed in the brain, and PRIP-2 (also known as PLC-L2), which exhibits a relatively ubiquitous expression. Experiments show both, PRIP-1 and PRIP-2, are involved in InsP3-mediated calcium signaling pathway and GABA(A)receptor-mediated signaling pathway. In addition, PRIP-2 acts as a negative regulator of B-cell receptor signaling and immune responses. Pssm-ID: 320036 [Multi-domain] Cd Length: 143 Bit Score: 40.66 E-value: 3.39e-03
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| RA | pfam00788 | Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); ... |
3263-3339 | 3.53e-03 | ||||||||||
Ras association (RalGDS/AF-6) domain; RasGTP effectors (in cases of AF6, canoe and RalGDS); putative RasGTP effectors in other cases. Recent evidence (not yet in MEDLINE) shows that some RA domains do NOT bind RasGTP. Predicted structure similar to that determined, and that of the RasGTP-binding domain of Raf kinase. Pssm-ID: 425871 Cd Length: 93 Bit Score: 39.24 E-value: 3.53e-03
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| EFh_PI-PLCdelta1 | cd16217 | EF-hand motif found in phosphoinositide phospholipase C delta 1 (PI-PLC-delta1); PI-PLC-delta1, ... |
2518-2571 | 4.21e-03 | ||||||||||
EF-hand motif found in phosphoinositide phospholipase C delta 1 (PI-PLC-delta1); PI-PLC-delta1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1 (PLCD1), or phospholipase C-III (PLC-III), or phospholipase C-delta-1 (PLC-delta-1), is present in high abundancy in the brain, heart, lung, skeletal muscle and testis. It is activated by high calcium levels generated by other PI-PLC family members, and therefore functions as a calcium amplifier within the cell. PI-PLC-delta1 is required for maintenance of homeostasis in skin and metabolic tissues. Moreover, it is essential in trophoblasts for placental development. Simultaneous loss of PI-PLC-delta1 may cause placental vascular defects, leading to embryonic lethality. PI-PLC-delta1 can be positively or negatively regulated by several binding partners, including p122/Rho GTPase activating protein (RhoGAP), Gha/Transglutaminase II, RalA, and calmodulin. It is involved in Alzheimer's disease and hypertension. Furthermore, PI-PLC-delta1 regulates cell proliferation and cell-cycle progression from G1- to S-phase by control of cyclin E-CDK2 activity and p27 levels. It can be activated by alpha1-adrenoreceptors (AR) in a calcium-dependent manner and may be important for G protein-coupled receptors (GPCR) responses in vascular smooth muscle (VSM). PI-PLC-delta1 may also be involved in noradrenaline (NA)-induced phosphatidylinositol-4,5-bisphosphate (PIP2) hydrolysis and modulate sustained contraction of mesenteric small arteries. In addition, it inhibits thermogenesis and induces lipid accumulation, and therefore contributes to the development of obesity. PI-PLC-delta1 contains a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. In addition, PI-PLC-delta1 possesses a classical leucine-rich nuclear export sequence (NES) located in the EF hand motifs, as well as a nuclear localization signal within its linker region, both of which may be responsible for translocating PI-PLC-delta1 into and out of the cell nucleus. Pssm-ID: 320047 [Multi-domain] Cd Length: 139 Bit Score: 40.11 E-value: 4.21e-03
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| EFh_PI-PLCbeta4 | cd16211 | EF-hand motif found in phosphoinositide phospholipase C beta 4 (PI-PLC-beta4); PI-PLC-beta4, ... |
2510-2568 | 4.73e-03 | ||||||||||
EF-hand motif found in phosphoinositide phospholipase C beta 4 (PI-PLC-beta4); PI-PLC-beta4, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4, or phospholipase C-beta-4 (PLC-beta4), is expressed in high concentrations in cerebellar Purkinje and granule cells, the median geniculate body, and the lateral geniculate nucleus. It may play a critical role in linking anxiety behaviors and theta rhythm heterogeneity. PI-PLC-beta4 is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It contributes to generate cell-specific Ca2+ signals evoked by G protein-coupled receptor stimulation. PI-PLC-beta4 functions as a downstream signaling molecule of type 1 metabotropic glutamate receptors (mGluR1s). The thalamic mGluR1-PI-PLC-beta4 cascade is essential for formalin-induced inflammatory pain by regulating the response of ventral posterolateral thalamic nucleus (VPL) neurons. Moreover, PI-PLC-beta4 is essential for long-term depression (LTD) in the rostral cerebellum, which may be required for the acquisition of the conditioned eyeblink response. Besides, PI-PLC-beta4 may play an important role in maintenance of the status epilepticus. The mutations of PI-PLC-beta4 has been identified as the major cause of autosomal dominant auriculocondylar syndrome (ACS). PI-PLC-beta4 contains a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. Besides, it has a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Pssm-ID: 320041 Cd Length: 153 Bit Score: 40.48 E-value: 4.73e-03
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| Ank_5 | pfam13857 | Ankyrin repeats (many copies); |
264-303 | 6.81e-03 | ||||||||||
Ankyrin repeats (many copies); Pssm-ID: 433530 [Multi-domain] Cd Length: 56 Bit Score: 37.33 E-value: 6.81e-03
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| PHA02878 | PHA02878 | ankyrin repeat protein; Provisional |
193-338 | 7.19e-03 | ||||||||||
ankyrin repeat protein; Provisional Pssm-ID: 222939 [Multi-domain] Cd Length: 477 Bit Score: 42.17 E-value: 7.19e-03
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