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Conserved domains on  [gi|1952584647|ref|XP_038678315|]
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1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-2a isoform X5 [Scyliorhinus canicula]

Protein Classification

PLC family C2 domain-containing protein( domain architecture ID 11598667)

PLC (phosphoinositide-specific phospholipase C) family C2 domain-containing protein similar to C2 domain region of PLCs that 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)

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PI-PLCc_GDPD_SF super family cl14615
Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases ...
 294-723 1.38e-146

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.


The actual alignment was detected with superfamily member cd08633:

Pssm-ID: 472694 [Multi-domain]  Cd Length: 254  Bit Score: 449.11  E-value: 1.38e-146
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  294 NQDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFRDVIETIN 373
Cdd:cd08633      1 NQDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  374 KYAFAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKLDVTSVHEEDMTQLPSPESLKGKILVKGKklpanisddaeeg 453
Cdd:cd08633     81 KYAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLDLSSVISNDCTRLPSPEILKGKILVKGK------------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  454 evsdedsadeieddcklmngdwkamanrkhvesvakkkldsllkeskirdredpdsfsvnaipqagkmcrkadskkkcss 533
Cdd:cd08633        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  534 gsvstvekpvsktedgtdsgedptsnkrhsrsfigsfskrkkktvkmkksssleddeedhdhqaaagrttvhmmrsgrqk 613
Cdd:cd08633        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  614 ktmKLSRALSDLVKYTKSVGMYDTDSEVMCSWQVSSYSETKTHQLLQQKPQQFVRMNQQQLSRIYPSSYRVDSSNFNPQP 693
Cdd:cd08633    148 ---KLSRALSDLVKYTKSVRVHDIETEATSSWQVSSFSETKAHQILQQKPAQYLRFNQRQLSRIYPSSYRVDSSNYNPQP 224

                          410       420       430
                   ....*....|....*....|....*....|
gi 1952584647  694 FWNAGCQLVALNYQSEGRVLQLNRAKFSSN 723
Cdd:cd08633    225 FWNAGCQMVALNYQSEGRMLQLNRAKFSAN 254
EFh_PI-PLC super family cl28895
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
 142-282 1.03e-91

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.


The actual alignment was detected with superfamily member cd16221:

Pssm-ID: 333715 [Multi-domain]  Cd Length: 141  Bit Score: 292.99  E-value: 1.03e-91
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  142 WLKQTFAEADKNGDGCLSVGEVLQLMHKLNVNLPRQKVKQMFKEADTDENQGTLDFEEFCAFYKMMSTRRDLYLLMLMYS 221
Cdd:cd16221      1 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEADTDDNQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1952584647  222 NHKDQLDTDDLKRFLEVEQKMKGVMKEHCLEIVDKFEPCLENQKQGVLGIDGFTNYMRSPA 282
Cdd:cd16221     81 NHKDHLDTNDLQRFLEVEQKMAGVTREHCLEIISQFEPCSENKQNGALGIDGFTNYMRSPA 141
PH_PLC_eta cd13364
Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of ...
 18-124 1.18e-52

Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of two enzymes, PLCeta1 and PLCeta2. They hydrolyze phosphatidylinositol 4,5-bisphosphate, are more sensitive to Ca2+ than other PLC isozymes, and involved in PKC activation in the brain and neuroendocrine systems. PLC-eta consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves by a variable linker, a C2 domain, and a C-terminal PDZ domain. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.involved in targeting proteins to the plasma membrane, but only a few (less than 10%) display strong specificity in binding inositol phosphates. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinases, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, cytoskeletal associated molecules, and in lipid associated enzymes.


:

Pssm-ID: 270170  Cd Length: 109  Bit Score: 180.17  E-value: 1.18e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647   18 MQSGTQMVKLRGGSKGLVRFYYLDEHKTCIRWRPSRKN-EKAKISIDAIREVCEGKQSEIFQRYP-DGSFDPNCCFSIYY 95
Cdd:cd13364      1 MQEGSELVKVRSNSRQYRRFFYLDEDKSSIRWKPSKKKsEKAKIPISSIREVREGKTTDIFRSCDiSGDFPEECCFSIIY 80

                           90       100
                   ....*....|....*....|....*....
gi 1952584647   96 GDHMESLDLVSSNGEEARTWITGLKYLMA 124
Cdd:cd13364     81 GEEYETLDLVASSPDEANIWITGLRYLMS 109
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 753-877 1.04e-51

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: 178.12  E-value: 1.04e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  753 KKQLVLRIISGQQLPKPKDsmlgDRGEIIDPFVEVEIIGL-AVDCFKEQTRVVDDNGFNPMWEETLVFTLYMPNLALVRF 831
Cdd:cd00275      1 PLTLTIKIISGQQLPKPKG----DKGSIVDPYVEVEIHGLpADDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRF 76

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1952584647  832 LVWDHDPIGRDFIGQRTLAFTSMMPGYRHVYL-----EGMEEASIFVHVAV 877
Cdd:cd00275     77 VVYDEDSGDDDFLGQACLPLDSLRQGYRHVPLldskgEPLELSTLFVHIDI 127
 
Name Accession Description Interval E-value
PI-PLCc_eta2 cd08633
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...
 294-723 1.38e-146

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: 449.11  E-value: 1.38e-146
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  294 NQDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFRDVIETIN 373
Cdd:cd08633      1 NQDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  374 KYAFAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKLDVTSVHEEDMTQLPSPESLKGKILVKGKklpanisddaeeg 453
Cdd:cd08633     81 KYAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLDLSSVISNDCTRLPSPEILKGKILVKGK------------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  454 evsdedsadeieddcklmngdwkamanrkhvesvakkkldsllkeskirdredpdsfsvnaipqagkmcrkadskkkcss 533
Cdd:cd08633        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  534 gsvstvekpvsktedgtdsgedptsnkrhsrsfigsfskrkkktvkmkksssleddeedhdhqaaagrttvhmmrsgrqk 613
Cdd:cd08633        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  614 ktmKLSRALSDLVKYTKSVGMYDTDSEVMCSWQVSSYSETKTHQLLQQKPQQFVRMNQQQLSRIYPSSYRVDSSNFNPQP 693
Cdd:cd08633    148 ---KLSRALSDLVKYTKSVRVHDIETEATSSWQVSSFSETKAHQILQQKPAQYLRFNQRQLSRIYPSSYRVDSSNYNPQP 224

                          410       420       430
                   ....*....|....*....|....*....|
gi 1952584647  694 FWNAGCQLVALNYQSEGRVLQLNRAKFSSN 723
Cdd:cd08633    225 FWNAGCQMVALNYQSEGRMLQLNRAKFSAN 254
EFh_PI-PLCeta2 cd16221
EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also ...
 142-282 1.03e-91

EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-2, or phosphoinositide phospholipase C-like 4, or phospholipase C-like protein 4 (PLC-L4), or phospholipase C-eta-2 (PLC-eta2), is a neuron-specific PI-PLC that is most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. It is also expressed in the pituitary gland, pineal gland, retina, and lung, as well as in neuroendocrine cells. PI-PLC-eta2 has been implicated in the regulation of neuronal differentiation/maturation. It is required for retinoic acid-stimulated neurite growth. It may also 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. Moreover, PI-PLC-eta2 acts as a Ca2+ sensor that shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Its activation can be triggered either by intracellular calcium mobilization or by G beta-gamma signaling. PI-PLC-eta2 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, 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. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases.


Pssm-ID: 320051 [Multi-domain]  Cd Length: 141  Bit Score: 292.99  E-value: 1.03e-91
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  142 WLKQTFAEADKNGDGCLSVGEVLQLMHKLNVNLPRQKVKQMFKEADTDENQGTLDFEEFCAFYKMMSTRRDLYLLMLMYS 221
Cdd:cd16221      1 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEADTDDNQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1952584647  222 NHKDQLDTDDLKRFLEVEQKMKGVMKEHCLEIVDKFEPCLENQKQGVLGIDGFTNYMRSPA 282
Cdd:cd16221     81 NHKDHLDTNDLQRFLEVEQKMAGVTREHCLEIISQFEPCSENKQNGALGIDGFTNYMRSPA 141
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
 297-439 3.02e-81

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: 263.21  E-value: 3.02e-81
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  297 MTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFRDVIETINKYA 376
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1952584647  377 FAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKLDVTSVhEEDMTQLPSPESLKGKILVKG 439
Cdd:pfam00388   81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPL-DDDLTELPSPEDLKGKILIKG 142
PLCXc smart00148
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...
 297-440 4.02e-62

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: 208.29  E-value: 4.02e-62
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647   297 MTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFRDVIETINKYA 376
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1952584647   377 FAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKLdVTSVHEEDMTQLPSPESLKGKILVKGK 440
Cdd:smart00148   81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDML-YTPPLTSSLEVLPSPEQLRGKILLKVR 143
PLN02952 PLN02952
phosphoinositide phospholipase C
 184-863 7.63e-54

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 199.84  E-value: 7.63e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  184 KEADTDENQGTLDFEEFCAF---YKMMSTR--RDLYLLMLMYSNHKDQLDTDDLKRFLEVEQKMKGVMKEHCLEIVDKfe 258
Cdd:PLN02952     6 KTESYNNDSGSYNYKMFNLFnrkFKITEAEppDDVKDVFCKFSVGGGHMGADQLRRFLVLHQDELDCTLAEAQRIVEE-- 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  259 pcLENQKQGV-------LGIDGFTNYMRSPagDIFNPEHYKVNQDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWV 331
Cdd:PLN02952    84 --VINRRHHVtrytrhgLNLDDFFHFLLYD--DLNGPITPQVHHDMTAPLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKA 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  332 LQTGCRCVEVDCWDGPDGEPI-VHHGYTLTSKILFRDVIETINKYAFAKSEYPVILSVENHCSVPQQKKMAQGLCEILGD 410
Cdd:PLN02952   160 LQRGVRVIELDLWPGSTKDEIlVLHGRTLTTPVPLIKCLKSIRDYAFSSSPYPVIITLEDHLTPDLQAKVAEMATQIFGQ 239

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  411 KLDVTsvHEEDMTQLPSPESLKGKILVKGKK-----LPANISDDAEEGEVS--DEDSADEIEDdcklmngdwkamanrkh 483
Cdd:PLN02952   240 MLYYP--ESDSLVQFPSPESLKHRIIISTKPpkeylESSGPIVIKKKNNVSpsGRNSSEETEE----------------- 300

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  484 vesvaKKKLDSLLKESKIRDREDPDsfsvnaipqagkmcrkadskkkcssgsvstvekpvsktedgtdsgedptsnkrhs 563
Cdd:PLN02952   301 -----AQTLESMLFEQEADSRSDSD------------------------------------------------------- 320

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  564 rsfigsfskrkkktvkmkkssslEDDEEDHDHQAAAGR--TTVHmmrSGRQKKTMKlsRALSDLVKYTKSVGMYDTDSEV 641
Cdd:PLN02952   321 -----------------------QDDNKSGELQKPAYKrlITIH---AGKPKGTLK--DAMKVAVDKVRRLSLSEQELEK 372

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  642 MCSwqvssysetkTHQllqqkpQQFVRMNQQQLSRIYPSSYRVDSSNFNPQPFWNAGCQLVALNYQSEGRVLQLNRAKFS 721
Cdd:PLN02952   373 AAT----------TNG------QDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFR 436

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  722 SNGNCGYVLKPKCMTQGTLNPTAEDLLTGQP-KKQLVLRIISGQQLPKPKDSMLGDRGEIIDPFVEVEIIGLAVDCFKEQ 800
Cdd:PLN02952   437 ANGGCGYLKKPDFLMKKGFHDEVFDPKKKLPvKKTLKVKVYLGDGWRLDFSHTHFDSYSPPDFYTKMYIVGVPADNAKKK 516

                          650       660       670       680       690       700
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1952584647  801 TRVVDDNgFNPMWEETLVFTLYMPNLALVRFLVWDHDPIGR-DFIGQRTLAFTSMMPGYRHVYL 863
Cdd:PLN02952   517 TKIIEDN-WYPAWNEEFSFPLTVPELALLRIEVREYDMSEKdDFGGQTCLPVSELRPGIRSVPL 579
PH_PLC_eta cd13364
Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of ...
 18-124 1.18e-52

Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of two enzymes, PLCeta1 and PLCeta2. They hydrolyze phosphatidylinositol 4,5-bisphosphate, are more sensitive to Ca2+ than other PLC isozymes, and involved in PKC activation in the brain and neuroendocrine systems. PLC-eta consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves by a variable linker, a C2 domain, and a C-terminal PDZ domain. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.involved in targeting proteins to the plasma membrane, but only a few (less than 10%) display strong specificity in binding inositol phosphates. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinases, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, cytoskeletal associated molecules, and in lipid associated enzymes.


Pssm-ID: 270170  Cd Length: 109  Bit Score: 180.17  E-value: 1.18e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647   18 MQSGTQMVKLRGGSKGLVRFYYLDEHKTCIRWRPSRKN-EKAKISIDAIREVCEGKQSEIFQRYP-DGSFDPNCCFSIYY 95
Cdd:cd13364      1 MQEGSELVKVRSNSRQYRRFFYLDEDKSSIRWKPSKKKsEKAKIPISSIREVREGKTTDIFRSCDiSGDFPEECCFSIIY 80

                           90       100
                   ....*....|....*....|....*....
gi 1952584647   96 GDHMESLDLVSSNGEEARTWITGLKYLMA 124
Cdd:cd13364     81 GEEYETLDLVASSPDEANIWITGLRYLMS 109
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 753-877 1.04e-51

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: 178.12  E-value: 1.04e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  753 KKQLVLRIISGQQLPKPKDsmlgDRGEIIDPFVEVEIIGL-AVDCFKEQTRVVDDNGFNPMWEETLVFTLYMPNLALVRF 831
Cdd:cd00275      1 PLTLTIKIISGQQLPKPKG----DKGSIVDPYVEVEIHGLpADDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRF 76

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1952584647  832 LVWDHDPIGRDFIGQRTLAFTSMMPGYRHVYL-----EGMEEASIFVHVAV 877
Cdd:cd00275     77 VVYDEDSGDDDFLGQACLPLDSLRQGYRHVPLldskgEPLELSTLFVHIDI 127
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 755-863 5.50e-20

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: 86.39  E-value: 5.50e-20
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647   755 QLVLRIISGQQLPKPkdsmlgDRGEIIDPFVEVEIIGlaVDCFKEQTRVVDDNGfNPMWEETLVFTLYMPNLALVRFLVW 834
Cdd:smart00239    1 TLTVKIISARNLPPK------DKGGKSDPYVKVSLDG--DPKEKKKTKVVKNTL-NPVWNETFEFEVPPPELAELEIEVY 71

                            90       100       110
                    ....*....|....*....|....*....|
gi 1952584647   835 DHDPIGRD-FIGQRTLAFTSMMPGYRHVYL 863
Cdd:smart00239   72 DKDRFGRDdFIGQVTIPLSDLLLGGRHEKL 101
C2 pfam00168
C2 domain;
755-860 2.11e-18

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 81.98  E-value: 2.11e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  755 QLVLRIISGQQLPKPkdsmlgDRGEIIDPFVEVEIIGlavDCFKEQTRVVDdNGFNPMWEETLVFTLYMPNLALVRFLVW 834
Cdd:pfam00168    2 RLTVTVIEAKNLPPK------DGNGTSDPYVKVYLLD---GKQKKKTKVVK-NTLNPVWNETFTFSVPDPENAVLEIEVY 71

                           90       100
                   ....*....|....*....|....*..
gi 1952584647  835 DHDPIGRD-FIGQRTLAFTSMMPGYRH 860
Cdd:pfam00168   72 DYDRFGRDdFIGEVRIPLSELDSGEGL 98
EF-hand_like pfam09279
Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...
 203-287 1.72e-14

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: 70.35  E-value: 1.72e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  203 FYKMMSTRRDLYLLMLMYSNHKDQLDTDDLKRFLEVEQKMKGVMKEHCLEIVDKFEPCLENQKQGVLGIDGFTNYMRSPA 282
Cdd:pfam09279    1 FYKMLTQREEIDEIFQEYSGDGQKLSLDELVDFLREEQREEDASPALALSLIERYEPSETAKKQHAMTKDGFLMYLCSPD 80


                   ....*
gi 1952584647  283 GDIFN 287
Cdd:pfam09279   81 GSIFN 85
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
132-203 2.82e-10

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 59.81  E-value: 2.82e-10
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1952584647  132 LSKRQRTRDQWLKQTFAEADKNGDGCLSVGEVLQLMHKLNVnlPRQKVKQMFKEADTDENqGTLDFEEFCAF 203
Cdd:COG5126     60 ESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTALGV--SEEEADELFARLDTDGD-GKISFEEFVAA 128
PH_12 pfam16457
Pleckstrin homology domain;
12-123 1.41e-09

Pleckstrin homology domain;


Pssm-ID: 465123 [Multi-domain]  Cd Length: 128  Bit Score: 57.65  E-value: 1.41e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647   12 ERCMSLMQSGTQMVKLRGGSKGL-VRFYYLDEHKTCIRW---------RPSRKNEKAKISIDAIREVCEGKQSEIF--QR 79
Cdd:pfam16457    3 EQRLNCLLEGAWFPKVRGRRRKKkYRFCRLSPNRKVLHYgdfeekptvDPSLESLPEKIDLSDIKEVVTGKECPHVreSG 82

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1952584647   80 YPDGSFDPNCCFSIYYGDHM-ESLDLVSSNGEEARTWITGLKYLM 123
Cdd:pfam16457   83 KKSKKTSSTLAFSLIYGADEyELLDFVAPSESVAAIWLDGLNMLL 127
PTZ00184 PTZ00184
calmodulin; Provisional
 144-210 6.87e-06

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 47.45  E-value: 6.87e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1952584647  144 KQTFAEADKNGDGCLSVGEVLQLMHKLNVNLPRQKVKQMFKEADTDENqGTLDFEEFCAfykMMSTR 210
Cdd:PTZ00184    14 KEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGN-GTIDFPEFLT---LMARK 76
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 178-207 2.98e-04

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 39.28  E-value: 2.98e-04
                            10        20        30
                    ....*....|....*....|....*....|
gi 1952584647   178 KVKQMFKEADTDENqGTLDFEEFCAFYKMM 207
Cdd:smart00054    1 ELKEAFRLFDKDGD-GKIDFEEFKDLLKAL 29
 
Name Accession Description Interval E-value
PI-PLCc_eta2 cd08633
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...
 294-723 1.38e-146

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: 449.11  E-value: 1.38e-146
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  294 NQDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFRDVIETIN 373
Cdd:cd08633      1 NQDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  374 KYAFAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKLDVTSVHEEDMTQLPSPESLKGKILVKGKklpanisddaeeg 453
Cdd:cd08633     81 KYAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLDLSSVISNDCTRLPSPEILKGKILVKGK------------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  454 evsdedsadeieddcklmngdwkamanrkhvesvakkkldsllkeskirdredpdsfsvnaipqagkmcrkadskkkcss 533
Cdd:cd08633        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  534 gsvstvekpvsktedgtdsgedptsnkrhsrsfigsfskrkkktvkmkksssleddeedhdhqaaagrttvhmmrsgrqk 613
Cdd:cd08633        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  614 ktmKLSRALSDLVKYTKSVGMYDTDSEVMCSWQVSSYSETKTHQLLQQKPQQFVRMNQQQLSRIYPSSYRVDSSNFNPQP 693
Cdd:cd08633    148 ---KLSRALSDLVKYTKSVRVHDIETEATSSWQVSSFSETKAHQILQQKPAQYLRFNQRQLSRIYPSSYRVDSSNYNPQP 224

                          410       420       430
                   ....*....|....*....|....*....|
gi 1952584647  694 FWNAGCQLVALNYQSEGRVLQLNRAKFSSN 723
Cdd:cd08633    225 FWNAGCQMVALNYQSEGRMLQLNRAKFSAN 254
PI-PLCc_eta1 cd08632
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily ...
 294-723 1.08e-117

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: 370.51  E-value: 1.08e-117
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  294 NQDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFRDVIETIN 373
Cdd:cd08632      1 NQDMDQPLCNYFIASSHNTYLTGDQLLSQSKVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKITFRDVIETIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  374 KYAFAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKLDVTSVHEEDMTQLPSPESLKGKILVKGKklpanisddaeeg 453
Cdd:cd08632     81 KYAFVKNEFPVILSIENHCSIQQQKKIAQYLKEIFGDKLDLSSVLTGDPKQLPSPQLLKGKILVKGK------------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  454 evsdedsadeieddcklmngdwkamanrkhvesvakkkldsllkeskirdredpdsfsvnaipqagkmcrkadskkkcss 533
Cdd:cd08632        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  534 gsvstvekpvsktedgtdsgedptsnkrhsrsfigsfskrkkktvkmkksssleddeedhdhqaaagrttvhmmrsgrqk 613
Cdd:cd08632        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  614 ktmKLSRALSDLVKYTKSVGMYD-TDSEVMCSwqVSSYSETKTHQLLQQKPQQFVRMNQQQLSRIYPSSYRVDSSNFNPQ 692
Cdd:cd08632    148 ---KLCRDLSDLVVYTNSVAAQDiVDDGSTGN--VLSFSETRAHQLVQQKAEQFMTYNQKQLTRIYPSAYRIDSSNFNPL 222

                          410       420       430
                   ....*....|....*....|....*....|.
gi 1952584647  693 PFWNAGCQLVALNYQSEGRVLQLNRAKFSSN 723
Cdd:cd08632    223 PYWNVGCQLVALNYQSEGRMMQLNRAKFMVN 253
PI-PLCc_eta cd08594
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family ...
 294-723 7.54e-115

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: 361.43  E-value: 7.54e-115
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  294 NQDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFRDVIETIN 373
Cdd:cd08594      1 NQDMTQPLSHYFIASSHNTYLTGDQLLSQSRVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKILFRDVIETIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  374 KYAFAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKLDVTSVHEEDmtqlpspeslkgkilvkGKKLPAnisddaeeg 453
Cdd:cd08594     81 KYAFIKNEYPVILSIENHCSVQQQKKMAQYLKEILGDKLDLSSVISGD-----------------SKQLPS--------- 134

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  454 evsdedsadeieddcklmngdwkamanrkhvesvakkkldsllkeskirdredPDSFSvnaipqaGKMcrkadskkkcss 533
Cdd:cd08594    135 -----------------------------------------------------PQSLK-------GKI------------ 142

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  534 gsvstvekpvsktedgtdsgedptsnkrhsrsfigsfskrkkktvkmkksssleddeedhdhqaaagrttvhmmrsgrqk 613
Cdd:cd08594        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  614 ktmklsralsdLVKYTKsvgmydtdsevmcsWQVSSYSETKTHQLLQQKPQQFVRMNQQQLSRIYPSSYRVDSSNFNPQP 693
Cdd:cd08594    143 -----------LIKGKK--------------WQVSSFSETRAHQIVQQKAAQFLRFNQRQLSRIYPSAYRIDSSNFNPQP 197

                          410       420       430
                   ....*....|....*....|....*....|
gi 1952584647  694 FWNAGCQLVALNYQSEGRVLQLNRAKFSSN 723
Cdd:cd08594    198 YWNAGCQLVALNYQTEGRMLQLNRAKFRAN 227
PI-PLCc_eukaryota cd08558
Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; ...
 295-723 3.00e-111

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: 351.37  E-value: 3.00e-111
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  295 QDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFRDVIETINK 374
Cdd:cd08558      2 QDMTQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGHTLTSKILFKDVIEAIKE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  375 YAFAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKLdVTSVHEEDMTQLPSPESLKGKILVKGKKlpanisddaeege 454
Cdd:cd08558     82 YAFVTSPYPVILSLENHCSLEQQKKMAQILKEIFGDKL-LTPPLDENPVQLPSPEQLKGKILIKGKK------------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  455 vsdedsadeieddcklmngdwkamanrKHVESVAKKKLDSLLKEskirdredpdsfsvnaipqagkmcrkadskkkcssg 534
Cdd:cd08558    148 ---------------------------YHMSSFSETKALKLLKE------------------------------------ 164

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  535 svstvekpvsktedgtdsgedptsnkrhsrsfigsfskrkkktvkmkksssleddeedhdhqaaagrttvhmmrsgrqkk 614
Cdd:cd08558        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  615 tmklsralsdlvkytksvgmydtdsevmcswqvssysetkthqllqqKPQQFVRMNQQQLSRIYPSSYRVDSSNFNPQPF 694
Cdd:cd08558    165 -----------------------------------------------SPEEFVKYNKRQLSRVYPKGTRVDSSNYNPQPF 197

                          410       420
                   ....*....|....*....|....*....
gi 1952584647  695 WNAGCQLVALNYQSEGRVLQLNRAKFSSN 723
Cdd:cd08558    198 WNAGCQMVALNYQTPDLPMQLNQGKFEQN 226
PI-PLCc_delta cd08593
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily ...
 295-723 1.51e-108

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: 345.09  E-value: 1.51e-108
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  295 QDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFRDVIETINK 374
Cdd:cd08593      2 QDMTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDGPDGEPIIYHGHTLTSKILFKDVIQAIRE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  375 YAFAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKLdVTSVHEEDMTQLPSPESLKGKILVKGKKLpanisddaeege 454
Cdd:cd08593     82 YAFKVSPYPVILSLENHCSVEQQKVMAQHLKSILGDKL-LTQPLDGVLTALPSPEELKGKILVKGKKL------------ 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  455 vsdedsadeieddcklmngdwkamanrkhvesvakkkldsllkeskirdredpdsfsvnaipqagkmcrkadskkkcssg 534
Cdd:cd08593        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  535 svstvekpvsktedgtdsgedptsnkrhsrsfigsfskrkkktvkmkksssleddeedhdhqaaagrttvhmmrsgrqkk 614
Cdd:cd08593        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  615 tmKLSRALSDLVKYTKSVGmYDTDSEVMCSW---QVSSYSETKTHQLLQQKPQQFVRMNQQQLSRIYPSSYRVDSSNFNP 691
Cdd:cd08593    149 --KLAKELSDLVIYCKSVH-FKSFEHSKENYhfyEMSSFSESKALKLAQESGNEFVRHNKRQLSRIYPAGLRTDSSNYDP 225

                          410       420       430
                   ....*....|....*....|....*....|..
gi 1952584647  692 QPFWNAGCQLVALNYQSEGRVLQLNRAKFSSN 723
Cdd:cd08593    226 QEMWNVGCQIVALNFQTPGEEMDLNDGLFRQN 257
EFh_PI-PLCeta2 cd16221
EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also ...
 142-282 1.03e-91

EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-2, or phosphoinositide phospholipase C-like 4, or phospholipase C-like protein 4 (PLC-L4), or phospholipase C-eta-2 (PLC-eta2), is a neuron-specific PI-PLC that is most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. It is also expressed in the pituitary gland, pineal gland, retina, and lung, as well as in neuroendocrine cells. PI-PLC-eta2 has been implicated in the regulation of neuronal differentiation/maturation. It is required for retinoic acid-stimulated neurite growth. It may also 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. Moreover, PI-PLC-eta2 acts as a Ca2+ sensor that shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Its activation can be triggered either by intracellular calcium mobilization or by G beta-gamma signaling. PI-PLC-eta2 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, 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. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases.


Pssm-ID: 320051 [Multi-domain]  Cd Length: 141  Bit Score: 292.99  E-value: 1.03e-91
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  142 WLKQTFAEADKNGDGCLSVGEVLQLMHKLNVNLPRQKVKQMFKEADTDENQGTLDFEEFCAFYKMMSTRRDLYLLMLMYS 221
Cdd:cd16221      1 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEADTDDNQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1952584647  222 NHKDQLDTDDLKRFLEVEQKMKGVMKEHCLEIVDKFEPCLENQKQGVLGIDGFTNYMRSPA 282
Cdd:cd16221     81 NHKDHLDTNDLQRFLEVEQKMAGVTREHCLEIISQFEPCSENKQNGALGIDGFTNYMRSPA 141
PI-PLCc_PRIP_metazoa cd08597
Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This ...
 295-723 1.66e-91

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: 297.41  E-value: 1.66e-91
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  295 QDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFRDVIETINK 374
Cdd:cd08597      2 QDMTQPLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDGPNGEPVIYHGHTLTSKISFRSVIEAINE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  375 YAFAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKLdVTSVHEEDMTQLPSPESLKGKILVKGKKLpanisddaeege 454
Cdd:cd08597     82 YAFVASEYPLILCIENHCSEKQQLVMAQYLKEIFGDKL-YTEPPNEGESYLPSPHDLKGKIIIKGKKL------------ 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  455 vsdedsadeieddcklmngdwkamanrkhvesvakkkldsllkeskirdredpdsfsvnaipqagkmcrkadskkkcssg 534
Cdd:cd08597        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  535 svstvekpvsktedgtdsgedptsnkrhsrsfigsfskrkkktvkmkksssleddeedhdhqaaagrttvhmmrsgrqkK 614
Cdd:cd08597    149 -------------------------------------------------------------------------------K 149

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  615 TMKLSRALSDLVKYTKSVGMYD--TDSEVMCSWQVSSYSETKTHQLLQQKPQQFVRMNQQQLSRIYPSSYRVDSSNFNPQ 692
Cdd:cd08597    150 RRKLCKELSDLVSLCKSVRFQDfpTSAQNQKYWEVCSFSENLARRLANEFPEDFVNYNKKFLSRVYPSPMRVDSSNYNPQ 229

                          410       420       430
                   ....*....|....*....|....*....|.
gi 1952584647  693 PFWNAGCQLVALNYQSEGRVLQLNRAKFSSN 723
Cdd:cd08597    230 DFWNCGCQIVAMNYQTPGLMMDLNTGKFLEN 260
EFh_PI-PLCeta cd16205
EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes ...
 142-282 1.41e-88

EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes represent a class of neuron-specific metazoan PI-PLCs that are most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. They are phosphatidylinositol 4,5-bisphosphate-hydrolyzing enzymes that are more sensitive to Ca2+ than other PI-PLC isozymes. They function as calcium sensors activated by small increases in intracellular calcium concentrations. They are also activated through G-protein-coupled receptor (GPCR) stimulation, and further mediate GPCR signalling pathways. PI-PLC-eta isozymes contain an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, 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. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases. There are two PI-PLC-eta isozymes (1-2). Aside from the PI-PLC-eta isozymes identified in mammals, their eukaryotic homologs are also present in this family.


Pssm-ID: 320035 [Multi-domain]  Cd Length: 141  Bit Score: 283.89  E-value: 1.41e-88
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  142 WLKQTFAEADKNGDGCLSVGEVLQLMHKLNVNLPRQKVKQMFKEADTDENQGTLDFEEFCAFYKMMSTRRDLYLLMLMYS 221
Cdd:cd16205      1 WLKQTFEEADKNGDGLLSIGEILQLMHKLNVNLPRRKVRQMFKEADTDDNQGTLDFEEFCAFYKMMSTRRELYLLLLSYS 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1952584647  222 NHKDQLDTDDLKRFLEVEQKMKGVMKEHCLEIVDKFEPCLENQKQGVLGIDGFTNYMRSPA 282
Cdd:cd16205     81 NKKDYLTLEDLARFLEVEQKMTNVTLEYCLDIIEKFEPSEENKKNGLLGIDGFTNYMRSPA 141
PI-PLCc_delta4 cd08631
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily ...
 295-723 7.59e-86

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: 281.07  E-value: 7.59e-86
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  295 QDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFRDVIETINK 374
Cdd:cd08631      2 QDMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDGPNGEPIVYHGHTFTSKILFKDVVAAVAQ 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  375 YAFAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKLDVTSVHEEDMTQLPSPESLKGKILVKGKKLpanisddaeege 454
Cdd:cd08631     82 YAFQVSDYPVILSLENHCGVEQQQTMAQHLTEILGEKLLSTTLDGVLPTQLPSPEELRGKILLKGKKI------------ 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  455 vsdedsadeieddcklmngdwkamanrkhvesvakkkldsllkeskirdredpdsfsvnaipqagkmcrkadskkkcssg 534
Cdd:cd08631        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  535 svstvekpvsktedgtdsgedptsnkrhsrsfigsfskrkkktvkmkksssleddeedhdhqaaagrttvhmmrsgrqkk 614
Cdd:cd08631        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  615 tmKLSRALSDLVKYTKSVGM--YDTDSEVMCSWQVSSYSETKTHQLLQQKPQQFVRMNQQQLSRIYPSSYRVDSSNFNPQ 692
Cdd:cd08631    150 --RLSPELSDCVIYCKSVSFrsFTHSREHYHFYEISSFTETKARKLIREAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQ 227

                          410       420       430
                   ....*....|....*....|....*....|.
gi 1952584647  693 PFWNAGCQLVALNYQSEGRVLQLNRAKFSSN 723
Cdd:cd08631    228 EMWNAGCQMVALNFQTAGLEMDLNDGLFRQN 258
PI-PLCc_delta1 cd08629
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily ...
 295-723 3.54e-82

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: 270.75  E-value: 3.54e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  295 QDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFRDVIETINK 374
Cdd:cd08629      2 QDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVLRAIRD 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  375 YAFAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKLdVTSVHEEDMTQLPSPESLKGKILVKGKKLpanisddaeege 454
Cdd:cd08629     82 YAFKASPYPVILSLENHCSLEQQRVMARHLRAILGPIL-LDQPLDGVTTSLPSPEQLKGKILLKGKKL------------ 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  455 vsdedsadeieddcklmngdwkamanrkhvesvakkkldsllkeskirdredpdsfsvnaipqagkmcrkadskkkcssg 534
Cdd:cd08629        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  535 svstvekpvsktedgtdsgedptsnkrhsrsfigsfskrkkktvkmkksssleddeedhdhqaaagrttvhmmrsgrqkk 614
Cdd:cd08629        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  615 tmKLSRALSDLVKYTKSV---GMYDTDSEVMCSWQVSSYSETKTHQLLQQKPQQFVRMNQQQLSRIYPSSYRVDSSNFNP 691
Cdd:cd08629    149 --KLVPELSDMIIYCKSVhfgGFSSPGTSGQAFYEMASFSESRALRLLQESGNGFVRHNVSCLSRIYPAGWRTDSSNYSP 226

                          410       420       430
                   ....*....|....*....|....*....|..
gi 1952584647  692 QPFWNAGCQLVALNYQSEGRVLQLNRAKFSSN 723
Cdd:cd08629    227 VEMWNGGCQIVALNFQTPGPEMDVYLGCFQDN 258
PI-PLCc_beta cd08591
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ...
 295-723 9.46e-82

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: 269.59  E-value: 9.46e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  295 QDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDG--PDGEPIVHHGYTLTSKILFRDVIETI 372
Cdd:cd08591      2 QDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGkgEDEEPIITHGKTMCTEILFKDVIEAI 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  373 NKYAFAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKLDVTSVHE---EDMTQLPSPESLKGKILVKGKKlpanisdd 449
Cdd:cd08591     82 AETAFKTSEYPVILSFENHCSSKQQAKMAEYCREIFGDLLLTEPLEKyplEPGVPLPSPNDLKRKILIKNKK-------- 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  450 aeegevsdedsadeieddcklmngdwkamanrkhvesvakkkldsllkeskirdredpdsfsvnaipqagkmcrkadskk 529
Cdd:cd08591        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  530 kcssgsvstvekpvsktedgtdsgedptsnkrhsrsfigsfskrkkktvkmkksssleddeedhdhqaaagrttvhmmrs 609
Cdd:cd08591        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  610 grqkktmklsraLSDLVKYTKSVGM--YDTDSEVMCSWQVSSYSETKTHQLLQQKPQQFVRMNQQQLSRIYPSSYRVDSS 687
Cdd:cd08591    154 ------------LSSLVNYIQPVKFqgFEVAEKRNKHYEMSSFNESKGLGYLKKSPIEFVNYNKRQLSRIYPKGTRVDSS 221

                          410       420       430
                   ....*....|....*....|....*....|....*.
gi 1952584647  688 NFNPQPFWNAGCQLVALNYQSEGRVLQLNRAKFSSN 723
Cdd:cd08591    222 NYMPQIFWNAGCQMVALNFQTPDLPMQLNQGKFEYN 257
PI-PLCc_gamma cd08592
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...
 294-723 2.74e-81

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: 266.98  E-value: 2.74e-81
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  294 NQDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFRDVIETIN 373
Cdd:cd08592      1 PQDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGPDGMPIIYHGHTLTSKIKFMDVLKTIK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  374 KYAFAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKLdVTSVHEEDMTQLPSPESLKGKILVKGKKLpanisddaeeg 453
Cdd:cd08592     81 EHAFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDML-LTQPVDRNADQLPSPNQLKRKIIIKHKKL----------- 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  454 evsdedsadeieddCKLMngdwkamanRKHVESVAKKKLdsllkeskirdredpdsfsvnaipqagkmcrkadskkkcss 533
Cdd:cd08592    149 --------------FYEM---------SSFPETKAEKYL----------------------------------------- 164

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  534 gsvstvekpvsktedgtdsgedptsNKRHSRSFIgsfskrkkktvkmkksssleddeedhdhqaaagrttvhmmrsgrqk 613
Cdd:cd08592    165 -------------------------NRQKGKIFL---------------------------------------------- 173

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  614 ktmklsralsdlvKYtksvgmydtdsevmcswqvssysetkthqllqqkpqqfvrmNQQQLSRIYPSSYRVDSSNFNPQP 693
Cdd:cd08592    174 -------------KY-----------------------------------------NRRQLSRVYPKGQRVDSSNYDPVP 199

                          410       420       430
                   ....*....|....*....|....*....|
gi 1952584647  694 FWNAGCQLVALNYQSEGRVLQLNRAKFSSN 723
Cdd:cd08592    200 MWNCGSQMVALNFQTPDKPMQLNQALFMLN 229
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
 297-439 3.02e-81

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: 263.21  E-value: 3.02e-81
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  297 MTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFRDVIETINKYA 376
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1952584647  377 FAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKLDVTSVhEEDMTQLPSPESLKGKILVKG 439
Cdd:pfam00388   81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPL-DDDLTELPSPEDLKGKILIKG 142
PI-PLCc_delta3 cd08630
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily ...
 295-723 4.79e-79

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: 261.88  E-value: 4.79e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  295 QDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFRDVIETINK 374
Cdd:cd08630      2 QDMSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVIQAVRQ 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  375 YAFAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKLDVTSVHEEDMTQLPSPESLKGKILVKGKKLpanisddaeege 454
Cdd:cd08630     82 HAFTASPYPVILSLENHCGLEQQAAMARHLQTILGDMLVTQPLDSLNPEELPSPEELKGRVLVKGKKL------------ 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  455 vsdedsadeieddcklmngdwkamanrkhvesvakkkldsllkeskirdredpdsfsvnaipqagkmcrkadskkkcssg 534
Cdd:cd08630        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  535 svstvekpvsktedgtdsgedptsnkrhsrsfigsfskrkkktvkmkksssleddeedhdhqaaagrttvhmmrsgrqkk 614
Cdd:cd08630        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  615 tmKLSRALSDLVKYTKSVGM--YDTDSEVMCSWQVSSYSETKTHQLLQQKPQQFVRMNQQQLSRIYPSSYRVDSSNFNPQ 692
Cdd:cd08630    150 --QISPELSALAVYCQATRLrtLEPAPVQPQPCQVSSLSERKAKKLIREAGNSFVRHNARQLTRVYPLGLRMNSANYSPQ 227

                          410       420       430
                   ....*....|....*....|....*....|.
gi 1952584647  693 PFWNAGCQLVALNYQSEGRVLQLNRAKFSSN 723
Cdd:cd08630    228 EMWNSGCQLVALNFQTPGYEMDLNAGRFLVN 258
PI-PLC1c_yeast cd08598
Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This ...
 294-723 1.45e-76

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: 253.32  E-value: 1.45e-76
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  294 NQDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFRDVIETIN 373
Cdd:cd08598      1 EEDLSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDGDDGEPVVTHGYTLTSSVPFRDVCRAIK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  374 KYAFAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKLdVTSVHEEDMTQLPSPESLKGKILVKGKKLPANISddaeeg 453
Cdd:cd08598     81 KYAFVTSPYPLILSLEVHCDAEQQERMVEIMKETFGDLL-VTEPLDGLEDELPSPEELRGKILIKVKKESKTPN------ 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  454 evsdedsadeieddcklmngdwkamanrkHVESVAKKKLDSLLKESKirdredpdsfsvnaipqagkmcrkadskkkcss 533
Cdd:cd08598    154 -----------------------------HIFSLSERSLLKLLKDKR--------------------------------- 171

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  534 gsvstveKPVSKtedgtdsgedptsnkrHSRSfigsfskrkkktvkmkksssleddeedhdhqaaagrttvHMMrsgrqk 613
Cdd:cd08598    172 -------AALDK----------------HNRR---------------------------------------HLM------ 183

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  614 ktmklsralsdlvkytksvgmydtdsevmcswqvssysetkthqllqqkpqqfvrmnqqqlsRIYPSSYRVDSSNFNPQP 693
Cdd:cd08598    184 --------------------------------------------------------------RVYPSGTRISSSNFNPLP 201

                          410       420       430
                   ....*....|....*....|....*....|
gi 1952584647  694 FWNAGCQLVALNYQSEGRVLQLNRAKFSSN 723
Cdd:cd08598    202 FWRAGVQMVALNWQTYDLGMQLNEAMFAGS 231
PI-PLCc_zeta cd08595
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family ...
 295-723 1.75e-76

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: 254.48  E-value: 1.75e-76
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  295 QDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFRDVIETINK 374
Cdd:cd08595      2 QDMDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDGADNEPVVYHGYTLTSKILFKEVITTVEK 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  375 YAFAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKLDVTSVHEEDMTQLPSPESLKGKILVKGKKlpanisddaeege 454
Cdd:cd08595     82 YAFEKSDYPVVLSLENHCSTEQQEIMAHYLVSILGEKLLRAPIDDPATGELPSPEALKFKILVKNKK------------- 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  455 vsdedsadeieddcklmngdwkamanrkhvesvakkkldsllkeskirdredpdsfsvnaipqagkmcrkadskkkcssg 534
Cdd:cd08595        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  535 svstvekpvsktedgtdsgedptsnkrhsrsfigsfskrkkktvkmkksssleddeedhdhqaaagrttvhmmrsgrqkk 614
Cdd:cd08595        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  615 tmKLSRALSDLVKYTKsvgmydtdSEVMCSWQVS----------SYSETKTHQLLQQKPQQFVRMNQQQLSRIYPSSYRV 684
Cdd:cd08595    149 --KIAKALSDLVIYTK--------SEKFCSFTHSrdnqhsyennSIGENKARKLLKSSGADFVGHTQRFITRIYPKGTRA 218

                          410       420       430
                   ....*....|....*....|....*....|....*....
gi 1952584647  685 DSSNFNPQPFWNAGCQLVALNYQSEGRVLQLNRAKFSSN 723
Cdd:cd08595    219 SSSNYNPQEFWNVGCQMVALNFQTLGAPMDLQNGKFLDN 257
EFh_PI-PLCeta1 cd16220
EF-hand motif found in phosphoinositide phospholipase C eta 1 (PI-PLC-eta1); PI-PLC-eta1, also ...
 142-282 1.21e-71

EF-hand motif found in phosphoinositide phospholipase C eta 1 (PI-PLC-eta1); PI-PLC-eta1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-1, or phospholipase C-eta-1 (PLC-eta-1), or phospholipase C-like protein 3 (PLC-L3), is a neuron-specific PI-PLC that is most abundant in the brain, particularly in the hippocampus, habenula, olfactory bulb, cerebellum, and throughout the cerebral cortex. It is also expressed in the zona incerta and in the spinal cord. PI-PLC-eta1 may perform a fundamental role in the brain. It may also act in synergy with other PLC subtypes. For instance, it is activated via intracellular Ca2+ mobilization and then plays a role in the amplification of GPCR (G-protein-coupled receptor)-mediated PLC-beta signals. In addition, its activity can be stimulated by ionomycin. PI-PLC-eta1 contains an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, 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. The C-terminal tail harbors a number of proline-rich motifs which may interact with SH3 (Src homology 3) domain-containing proteins, as well as many serine/threonine residues, suggesting possible regulation of interactions by protein kinases/phosphatases.


Pssm-ID: 320050 [Multi-domain]  Cd Length: 141  Bit Score: 235.69  E-value: 1.21e-71
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  142 WLKQTFAEADKNGDGCLSVGEVLQLMHKLNVNLPRQKVKQMFKEADTDENQGTLDFEEFCAFYKMMSTRRDLYLLMLMYS 221
Cdd:cd16220      1 WVKQTFEEADKNGDGLLNIEEIYQLMHKLNVNLPRRKVRQMFQEADTDENQGTLTFEEFCVFYKMMSLRRDLYLLLLSYS 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1952584647  222 NHKDQLDTDDLKRFLEVEQKMKGVMKEHCLEIVDKFEPCLENQKQGVLGIDGFTNYMRSPA 282
Cdd:cd16220     81 DKKDHLTVEELAQFLKVEQKMNNVTTEYCLDIIKKFEVSEENKEQNVLGIEGFTNFMRSPA 141
PI-PLCc_gamma2 cd08628
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily ...
 295-723 4.58e-71

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: 238.80  E-value: 4.58e-71
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  295 QDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFRDVIETINK 374
Cdd:cd08628      2 QDMNNPLSHYWISSSHNTYLTGDQLRSESSTEAYIRCLRMGCRCIELDCWDGPDGKPIIYHGWTRTTKIKFDDVVQAIKD 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  375 YAFAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKLdVTSVHEEDMTQLPSPESLKGKILVKGKKLPANisddaeegE 454
Cdd:cd08628     82 HAFVTSEYPVILSIEEHCSVEQQRHMAKVFKEVFGDKL-LMKPLEASADQLPSPTQLKEKIIIKHKKLIAI--------E 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  455 VSDedsadeieddcklmngdwkamanrkhvesvakkkldsllkeskirdredpdsfsvnaipqagkmcrkadskkkcssg 534
Cdd:cd08628    153 LSD----------------------------------------------------------------------------- 155

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  535 sVSTVEKPVSKTEDGTdsgEDPTSnkRHSRSFIgsfskrkkktvkmkksssleddeedhdhqaaagrttvhmmrsgrqkk 614
Cdd:cd08628    156 -LVVYCKPTSKTKDNL---ENPDF--KEIRSFV----------------------------------------------- 182

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  615 tmklsralsdlvkytksvgmydtdsevmcswqvssysETKTHQLLQQKPQQFVRMNQQQLSRIYPSSYRVDSSNFNPQPF 694
Cdd:cd08628    183 -------------------------------------ETKAPSIIRQKPVQLLKYNRKGLTRVYPKGQRVDSSNYDPFRL 225

                          410       420
                   ....*....|....*....|....*....
gi 1952584647  695 WNAGCQLVALNYQSEGRVLQLNRAKFSSN 723
Cdd:cd08628    226 WLCGSQMVALNFQTADKYMQLNHALFSLN 254
PI-PLCc_epsilon cd08596
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ...
 295-723 8.56e-69

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: 232.05  E-value: 8.56e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  295 QDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFRDVIETINK 374
Cdd:cd08596      2 EDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGDDGMPIIYHGHTLTTKIPFKDVVEAINR 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  375 YAFAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKLDVTSVHEEDMT---QLPSPESLKGKILVKGKKLPanisddae 451
Cdd:cd08596     82 SAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLVTKFLFESDFSddpSLPSPLQLKNKILLKNKKAP-------- 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  452 egevsdedsadeieddcklmngdwkamanrkhvesvakkkldsllkeskirdredpdsfsvnaipqagkmcrkadskkkc 531
Cdd:cd08596        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  532 ssgsvstvekpvsktedgtdsgedptsnkrhsrsfigsfskrkkktvkmkksssleddeedhdhqaaagrttvhmmrsgr 611
Cdd:cd08596        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  612 qkktmklsrALSDLVKYTKSVgMYDTDSEVMCsWQVSSYSETKTHQLLQQKPQQFVRMNQQQLSRIYPSSYRVDSSNFNP 691
Cdd:cd08596    154 ---------ELSDLVIYCQAV-KFPGLSTPKC-YHISSLNENAAKRLCRRYPQKLVQHTRCQLLRTYPAATRIDSSNPNP 222

                          410       420       430
                   ....*....|....*....|....*....|..
gi 1952584647  692 QPFWNAGCQLVALNYQSEGRVLQLNRAKFSSN 723
Cdd:cd08596    223 LIFWLHGLQLVALNYQTDDLPMHLNAAMFEAN 254
PI-PLCc_beta4 cd08626
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily ...
 295-723 5.38e-65

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: 221.18  E-value: 5.38e-65
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  295 QDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGP--DGEPIVHHGYTLTSKILFRDVIETI 372
Cdd:cd08626      2 QDMDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGKgeDQEPIITHGKAMCTDILFKDVIQAI 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  373 NKYAFAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKL---DVTSVHEEDMTQLPSPESLKGKILVKGKKlpanisdd 449
Cdd:cd08626     82 KDTAFVTSDYPVILSFENHCSKPQQYKLAKYCEEIFGDLLltkPLESHPLEPGVPLPSPNKLKRKILIKNKR-------- 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  450 aeegevsdedsadeieddcklmngdwkamanrkhvesvakkkldsllkeskirdredpdsfsvnaipqagkmcrkadskk 529
Cdd:cd08626        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  530 kcssgsvstvekpvsktedgtdsgedptsnkrhsrsfigsfskrkkktvkmkksssleddeedhdhqaaagrttvhmmrs 609
Cdd:cd08626        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  610 grqkktmklsraLSDLVKYTKSVGM--YDTDSEVMCSWQVSSYSETKTHQLLQQKPQQFVRMNQQQLSRIYPSSYRVDSS 687
Cdd:cd08626    154 ------------LSSLVNYAQPVKFqgFDVAEERNIHFNMSSFNESVGLGYLKTSAIEFVNYNKRQMSRIYPKGTRVDSS 221

                          410       420       430
                   ....*....|....*....|....*....|....*.
gi 1952584647  688 NFNPQPFWNAGCQLVALNYQSEGRVLQLNRAKFSSN 723
Cdd:cd08626    222 NYMPQIFWNAGCQMVSLNFQTPDLGMQLNQGKFEYN 257
PI-PLCc_beta2 cd08624
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily ...
 295-723 3.52e-62

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: 213.38  E-value: 3.52e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  295 QDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDG--PDGEPIVHHGYTLTSKILFRDVIETI 372
Cdd:cd08624      2 QDMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTEILFKDAIEAI 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  373 NKYAFAKSEYPVILSVENHC-SVPQQKKMAQGLCEILGDKLDVTSVHEEDM---TQLPSPESLKGKILVKGKKlpanisd 448
Cdd:cd08624     82 AESAFKTSPYPVILSFENHVdSPKQQAKMAEYCRTIFGDMLLTEPLEKYPLkpgVPLPSPEDLRGKILIKNKK------- 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  449 daeegevsdedsadeieddcklmngdWKAMANrkhvesvakkkLDSLLKESKIrdredpDSFSVNAipqagkmcrkadsk 528
Cdd:cd08624    155 --------------------------YEEMSS-----------LVNYIQPTKF------VSFEFSA-------------- 177

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  529 kkcssgsvstvekpvsktedgtdsgedptsnkRHSRSFIgsfskrkkktvkmkksssleddeedhdhqaaagrttvhmmr 608
Cdd:cd08624    178 --------------------------------QKNRSYV----------------------------------------- 184

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  609 sgrqkktmklsralsdlvkytksvgmydtdsevmcswqVSSYSETKTHQLLQQKPQQFVRMNQQQLSRIYPSSYRVDSSN 688
Cdd:cd08624    185 --------------------------------------ISSFTELKAYDLLSKASVQFVEYNKRQMSRIYPKGTRMDSSN 226

                          410       420       430
                   ....*....|....*....|....*....|....*
gi 1952584647  689 FNPQPFWNAGCQLVALNYQSEGRVLQLNRAKFSSN 723
Cdd:cd08624    227 YMPQMFWNVGCQMVALNFQTMDLPMQQNMALFEFN 261
PLCXc smart00148
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...
 297-440 4.02e-62

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: 208.29  E-value: 4.02e-62
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647   297 MTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFRDVIETINKYA 376
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1952584647   377 FAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKLdVTSVHEEDMTQLPSPESLKGKILVKGK 440
Cdd:smart00148   81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDML-YTPPLTSSLEVLPSPEQLRGKILLKVR 143
PI-PLCc_beta3 cd08625
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily ...
 296-723 3.16e-60

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: 207.60  E-value: 3.16e-60
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  296 DMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDG--PDGEPIVHHGYTLTSKILFRDVIETIN 373
Cdd:cd08625      3 DMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGrpPEEEPFITHGFTMTTEIPFKDVIEAIA 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  374 KYAFAKSEYPVILSVENHC-SVPQQKKMAQGLCEILGDKLDVTSVHEEDM---TQLPSPESLKGKILVKGKKLPAnisdd 449
Cdd:cd08625     83 ESAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDKYPLvpgVQLPSPQELMGKILVKNKKMST----- 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  450 aeegevsdedsadeieddckLMNgdwkamanrkHVESVAKKKLDSllkeskirdredpdsfsvnaipqagkmcrkADSKK 529
Cdd:cd08625    158 --------------------LVN----------YIEPVKFKSFEA------------------------------AAKRN 177

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  530 KCssgsvstvekpvsktedgtdsgedptsnkrhsrsfigsfskrkkktvkmkksssleddeedhdhqaaagrttvhmmrs 609
Cdd:cd08625    178 KF------------------------------------------------------------------------------ 179

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  610 grqkktmklsralsdlvkytksvgmydtdsevmcsWQVSSYSETKTHQLLQQKPQQFVRMNQQQLSRIYPSSYRVDSSNF 689
Cdd:cd08625    180 -----------------------------------FEMSSFVETKAMEQLTKSPMEFVEYNKKQLSRIYPKGTRVDSSNY 224

                          410       420       430
                   ....*....|....*....|....*....|....
gi 1952584647  690 NPQPFWNAGCQLVALNYQSEGRVLQLNRAKFSSN 723
Cdd:cd08625    225 MPQLFWNVGCQMVALNFQTLDLAMQLNMGVFEYN 258
PI-PLCc_gamma1 cd08627
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily ...
 295-451 3.60e-59

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: 203.72  E-value: 3.60e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  295 QDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFRDVIETINK 374
Cdd:cd08627      2 EEMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKE 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1952584647  375 YAFAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKLdVTSVHEEDMTQLPSPESLKGKILVKGKKLPANISDDAE 451
Cdd:cd08627     82 HAFVTSEYPIILSIEDHCSIVQQRNMAQHFKKVFGDML-LTKPVDINADGLPSPNQLKRKILIKHKKLYRDMSSFPE 157
PI-PLCc_plant cd08599
Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family ...
 295-465 1.91e-54

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: 189.89  E-value: 1.91e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  295 QDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFRDVIETINK 374
Cdd:cd08599      2 HDMTAPLSHYFIFSSHNSYLTGNQLSSRSSTAPIIEALLRGCRVIELDLWPGGRGDICVLHGGTLTKPVKFEDCIKAIKE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  375 YAFAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKLDVTSVHEEdMTQLPSPESLKGKILV--KGKKLPANISDDAEE 452
Cdd:cd08599     82 NAFTASEYPVIITLENHLSPELQAKAAQILRETLGDKLFYPDSEDL-PEEFPSPEELKGKILIsdKPPVIRNSLSETQLK 160

                          170
                   ....*....|...
gi 1952584647  453 GEVSDEDSADEIE 465
Cdd:cd08599    161 KVIEGEHPTDLIE 173
PLN02952 PLN02952
phosphoinositide phospholipase C
 184-863 7.63e-54

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 199.84  E-value: 7.63e-54
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  184 KEADTDENQGTLDFEEFCAF---YKMMSTR--RDLYLLMLMYSNHKDQLDTDDLKRFLEVEQKMKGVMKEHCLEIVDKfe 258
Cdd:PLN02952     6 KTESYNNDSGSYNYKMFNLFnrkFKITEAEppDDVKDVFCKFSVGGGHMGADQLRRFLVLHQDELDCTLAEAQRIVEE-- 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  259 pcLENQKQGV-------LGIDGFTNYMRSPagDIFNPEHYKVNQDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWV 331
Cdd:PLN02952    84 --VINRRHHVtrytrhgLNLDDFFHFLLYD--DLNGPITPQVHHDMTAPLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKA 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  332 LQTGCRCVEVDCWDGPDGEPI-VHHGYTLTSKILFRDVIETINKYAFAKSEYPVILSVENHCSVPQQKKMAQGLCEILGD 410
Cdd:PLN02952   160 LQRGVRVIELDLWPGSTKDEIlVLHGRTLTTPVPLIKCLKSIRDYAFSSSPYPVIITLEDHLTPDLQAKVAEMATQIFGQ 239

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  411 KLDVTsvHEEDMTQLPSPESLKGKILVKGKK-----LPANISDDAEEGEVS--DEDSADEIEDdcklmngdwkamanrkh 483
Cdd:PLN02952   240 MLYYP--ESDSLVQFPSPESLKHRIIISTKPpkeylESSGPIVIKKKNNVSpsGRNSSEETEE----------------- 300

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  484 vesvaKKKLDSLLKESKIRDREDPDsfsvnaipqagkmcrkadskkkcssgsvstvekpvsktedgtdsgedptsnkrhs 563
Cdd:PLN02952   301 -----AQTLESMLFEQEADSRSDSD------------------------------------------------------- 320

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  564 rsfigsfskrkkktvkmkkssslEDDEEDHDHQAAAGR--TTVHmmrSGRQKKTMKlsRALSDLVKYTKSVGMYDTDSEV 641
Cdd:PLN02952   321 -----------------------QDDNKSGELQKPAYKrlITIH---AGKPKGTLK--DAMKVAVDKVRRLSLSEQELEK 372

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  642 MCSwqvssysetkTHQllqqkpQQFVRMNQQQLSRIYPSSYRVDSSNFNPQPFWNAGCQLVALNYQSEGRVLQLNRAKFS 721
Cdd:PLN02952   373 AAT----------TNG------QDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFR 436

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  722 SNGNCGYVLKPKCMTQGTLNPTAEDLLTGQP-KKQLVLRIISGQQLPKPKDSMLGDRGEIIDPFVEVEIIGLAVDCFKEQ 800
Cdd:PLN02952   437 ANGGCGYLKKPDFLMKKGFHDEVFDPKKKLPvKKTLKVKVYLGDGWRLDFSHTHFDSYSPPDFYTKMYIVGVPADNAKKK 516

                          650       660       670       680       690       700
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1952584647  801 TRVVDDNgFNPMWEETLVFTLYMPNLALVRFLVWDHDPIGR-DFIGQRTLAFTSMMPGYRHVYL 863
Cdd:PLN02952   517 TKIIEDN-WYPAWNEEFSFPLTVPELALLRIEVREYDMSEKdDFGGQTCLPVSELRPGIRSVPL 579
PH_PLC_eta cd13364
Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of ...
 18-124 1.18e-52

Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of two enzymes, PLCeta1 and PLCeta2. They hydrolyze phosphatidylinositol 4,5-bisphosphate, are more sensitive to Ca2+ than other PLC isozymes, and involved in PKC activation in the brain and neuroendocrine systems. PLC-eta consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves by a variable linker, a C2 domain, and a C-terminal PDZ domain. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.involved in targeting proteins to the plasma membrane, but only a few (less than 10%) display strong specificity in binding inositol phosphates. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinases, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, cytoskeletal associated molecules, and in lipid associated enzymes.


Pssm-ID: 270170  Cd Length: 109  Bit Score: 180.17  E-value: 1.18e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647   18 MQSGTQMVKLRGGSKGLVRFYYLDEHKTCIRWRPSRKN-EKAKISIDAIREVCEGKQSEIFQRYP-DGSFDPNCCFSIYY 95
Cdd:cd13364      1 MQEGSELVKVRSNSRQYRRFFYLDEDKSSIRWKPSKKKsEKAKIPISSIREVREGKTTDIFRSCDiSGDFPEECCFSIIY 80

                           90       100
                   ....*....|....*....|....*....
gi 1952584647   96 GDHMESLDLVSSNGEEARTWITGLKYLMA 124
Cdd:cd13364     81 GEEYETLDLVASSPDEANIWITGLRYLMS 109
PI-PLC-Y pfam00387
Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to ...
 622-734 3.26e-52

Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to form a single structural unit.


Pssm-ID: 459794  Cd Length: 114  Bit Score: 178.81  E-value: 3.26e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  622 LSDLVKYTKSVGMYD-TDSEVMCSWQVSSYSETKTHQLLQQKPQQFVRMNQQQLSRIYPSSYRVDSSNFNPQPFWNAGCQ 700
Cdd:pfam00387    1 LSDLVVYTQSVKFKSfSTPESKTPNHIFSFSESKALKLIKSSSAAFVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNCGVQ 80

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1952584647  701 LVALNYQSEGRVLQLNRAKFSSNGNCGYVLKPKC 734
Cdd:pfam00387   81 MVALNWQTPDEGMQLNEGMFADNGGCGYVLKPEF 114
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 753-877 1.04e-51

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: 178.12  E-value: 1.04e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  753 KKQLVLRIISGQQLPKPKDsmlgDRGEIIDPFVEVEIIGL-AVDCFKEQTRVVDDNGFNPMWEETLVFTLYMPNLALVRF 831
Cdd:cd00275      1 PLTLTIKIISGQQLPKPKG----DKGSIVDPYVEVEIHGLpADDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRF 76

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1952584647  832 LVWDHDPIGRDFIGQRTLAFTSMMPGYRHVYL-----EGMEEASIFVHVAV 877
Cdd:cd00275     77 VVYDEDSGDDDFLGQACLPLDSLRQGYRHVPLldskgEPLELSTLFVHIDI 127
PI-PLCc_beta1 cd08623
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily ...
 294-723 1.01e-50

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: 180.28  E-value: 1.01e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  294 NQDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDG--PDGEPIVHHGYTLTSKILFRDVIET 371
Cdd:cd08623      1 NEDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGrtAEEEPVITHGFTMTTEISFKEVIEA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  372 INKYAFAKSEYPVILSVENHCSVP-QQKKMAQGLCEILGDKLDVTSVHE---EDMTQLPSPESLKGKILVKGKKlpanis 447
Cdd:cd08623     81 IAECAFKTSPFPILLSFENHVDSPkQQAKMAEYCRLIFGDALLMEPLEKyplESGVPLPSPMDLMYKILVKNKK------ 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  448 ddaeegevsdedsadeieddcklmngdwkamanrkhvesvakkkldsllkeskirdredpdsfsvnaipqagkmcrkads 527
Cdd:cd08623        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  528 kkkcssgsvstvekpvsktedgtdsgedptsnkrhsrsfigsfskrkkktvkmkksssleddeedhdhqaaagrttvhmm 607
Cdd:cd08623        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  608 rsgrqkktmklsraLSDLVKYTKSVGM--YDTDSEVMCSWQVSSYSETKTHQLLQQKPQQFVRMNQQQLSRIYPSSYRVD 685
Cdd:cd08623    155 --------------MSNLVNYIQPVKFesFEASKKRNKSFEMSSFVETKGLEQLTKSPVEFVEYNKMQLSRIYPKGTRVD 220

                          410       420       430
                   ....*....|....*....|....*....|....*...
gi 1952584647  686 SSNFNPQPFWNAGCQLVALNYQSEGRVLQLNRAKFSSN 723
Cdd:cd08623    221 SSNYMPQLFWNAGCQMVALNFQTVDLSMQINMGMYEYN 258
PLN02228 PLN02228
Phosphoinositide phospholipase C
 225-863 1.14e-50

Phosphoinositide phospholipase C


Pssm-ID: 177873 [Multi-domain]  Cd Length: 567  Bit Score: 189.86  E-value: 1.14e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  225 DQLDTDDLKRFLEVEQKMKGVMKEHCLEIVDKFEPCLENQKQGVLGIDGFTNYMRSPagdiFN---PEHYKVNQDMTQPM 301
Cdd:PLN02228    37 GKMSFDELLRFVSEVQGERHAGLDYVQDIFHSVKHHNVFHHHGLVHLNAFYRYLFSD----TNsplPMSGQVHHDMKAPL 112

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  302 SDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGPDG-EPIVHHGYTLTSKILFRDVIETINKYAFAKS 380
Cdd:PLN02228   113 SHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSGnAAEVRHGRTLTSHEDLQKCLNAIKDNAFQVS 192

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  381 EYPVILSVENHCSVPQQKKMAQGLCEILGDKLdvTSVHEEDMTQLPSPESLKGKILVKGKKlpaniSDDAEEGEVSDEDS 460
Cdd:PLN02228   193 DYPVVITLEDHLPPNLQAQVAKMLTKTFRGML--FRCTSESTKHFPSPEELKNKILISTKP-----PKEYLESKTVQTTR 265

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  461 ADEIEDDcklmngDWKAMANRKhvESVAKKKLDslLKESKIRDRedpDSFSVNAipqagkmCRKADSKKKCSSGsvstve 540
Cdd:PLN02228   266 TPTVKET------SWKRVADAE--NKILEEYKD--EESEAVGYR---DLIAIHA-------ANCKDPLKDCLSD------ 319

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  541 kpvsktedgtdsgeDPTSNKRHSRSfigsfskrkkktvkmkkSSSLEddeedhdhqaaagrttvhmmrsgrqkkTMKLSR 620
Cdd:PLN02228   320 --------------DPEKPIRVSMD-----------------EQWLE---------------------------TMVRTR 341

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  621 AlSDLVKYTksvgmydtdsevmcswqvssysetkthqllqqkpqqfvrmnQQQLSRIYPSSYRVDSSNFNPQPFWNAGCQ 700
Cdd:PLN02228   342 G-TDLVRFT-----------------------------------------QRNLVRIYPKGTRVDSSNYDPHVGWTHGAQ 379

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  701 LVALNYQSEGRVLQLNRAKFSSNGNCGYVLKPKC-MTQGTLNPTAEDLLTgqpKKQLVLRIISGQ--QLPKPKDSMlgDR 777
Cdd:PLN02228   380 MVAFNMQGHGKQLWIMQGMFRANGGCGYVKKPRIlLDEHTLFDPCKRLPI---KTTLKVKIYTGEgwDLDFHLTHF--DQ 454

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  778 GEIIDPFVEVEIIGLAVDCFKEQTRVVDDNGFnPMW-EETLVFTLYMPNLALVRFLVWDHDP-IGRDFIGQRTLAFTSMM 855
Cdd:PLN02228   455 YSPPDFFVKIGIAGVPRDTVSYRTETAVDQWF-PIWgNDEFLFQLRVPELALLWFKVQDYDNdTQNDFAGQTCLPLPELK 533


                   ....*...
gi 1952584647  856 PGYRHVYL 863
Cdd:PLN02228   534 SGVRAVRL 541
PLN02222 PLN02222
phosphoinositide phospholipase C 2
 211-863 1.68e-50

phosphoinositide phospholipase C 2


Pssm-ID: 177868 [Multi-domain]  Cd Length: 581  Bit Score: 189.47  E-value: 1.68e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  211 RDLYLLMLMYSNhKDQLDTDDLKRFLEVEQKMKGVMKEHCLEIVDKFEPCLenQKQGvLGIDGFTNYMrspAGDIFNP-E 289
Cdd:PLN02222    25 REIKTIFEKYSE-NGVMTVDHLHRFLIDVQKQDKATREDAQSIINSASSLL--HRNG-LHLDAFFKYL---FGDNNPPlA 97

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  290 HYKVNQDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGPDGEPI-VHHGYTLTSKILFRDV 368
Cdd:PLN02222    98 LHEVHHDMDAPISHYFIFTGHNSYLTGNQLSSDCSEVPIIDALKKGVRVIELDIWPNSDKDDIdVLHGMTLTTPVGLIKC 177

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  369 IETINKYAFAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKLdVTSVHEEDMTQLPSPESLKGKILVKGKKlpanisd 448
Cdd:PLN02222   178 LKAIRAHAFDVSDYPVVVTLEDHLTPDLQSKVAEMVTEIFGEIL-FTPPVGESLKEFPSPNSLKKRIIISTKP------- 249

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  449 DAEEGEVSDedsaDEIEDDCKLMnGDwkamanrkhvESVAKKKLDSLLKESKIRDREDpdsfsvnaipqagkmcrkadsk 528
Cdd:PLN02222   250 PKEYKEGKD----DEVVQKGKDL-GD----------EEVWGREVPSFIQRNKSVDKND---------------------- 292

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  529 kkcssgsvstvekpvsktEDGTDSGEDptsnkrhsrsfigsfskrkkktvkmkkssslEDDEEDHDHQAAAGRTTVHMMR 608
Cdd:PLN02222   293 ------------------SNGDDDDDD-------------------------------DDGEDKSKKNAPPQYKHLIAIH 323

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  609 SGRQKKtmklsrALSDLVKytksvgmYDTDSEvmcswQVSSYSETKTHQLLQQKPQQFVRMNQQQLSRIYPSSYRVDSSN 688
Cdd:PLN02222   324 AGKPKG------GITECLK-------VDPDKV-----RRLSLSEEQLEKAAEKYAKQIVRFTQHNLLRIYPKGTRVTSSN 385

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  689 FNPQPFWNAGCQLVALNYQSEGRVLQLNRAKFSSNGNCGYVLKPKCMTQGTLNPTAEDLLTGQP-KKQLVLRIISGQQLP 767
Cdd:PLN02222   386 YNPLVGWSHGAQMVAFNMQGYGRSLWLMQGMFRANGGCGYIKKPDLLLKSGSDSDIFDPKATLPvKTTLRVTIYMGEGWY 465

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  768 KPKDSMLGDRGEIIDPFVEVEIIGLAVDCFKEQTRVVDDNgFNPMWEETLVFTLYMPNLALVRFLVWDHDPIGR-DFIGQ 846
Cdd:PLN02222   466 FDFRHTHFDQYSPPDFYTRVGIAGVPGDTVMKKTKTLEDN-WIPAWDEVFEFPLTVPELALLRLEVHEYDMSEKdDFGGQ 544

                          650
                   ....*....|....*..
gi 1952584647  847 RTLAFTSMMPGYRHVYL 863
Cdd:PLN02222   545 TCLPVWELSQGIRAFPL 561
PLCYc smart00149
Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ...
 623-735 6.06e-46

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: 160.87  E-value: 6.06e-46
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647   623 SDLVKYTKSV--GMYDTDSEVMCSWQVSSYSETKTHQLLQQKPQQFVRMNQQQLSRIYPSSYRVDSSNFNPQPFWNAGCQ 700
Cdd:smart00149    1 SDLVIYCAPVkfRSFESAESKNPFYEMSSFSETKAKKLLKKSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGCQ 80

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 1952584647   701 LVALNYQSEGRVLQLNRAKFSSNGNCGYVLKPKCM 735
Cdd:smart00149   81 MVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115
EFh_PRIP cd16206
EF-hand motif found in phospholipase C-related but catalytically inactive proteins (PRIP); ...
 142-281 7.56e-46

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: 161.99  E-value: 7.56e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  142 WLKQTFAEADKNGDGCLSVGEVLQLMHKLNVNLPRQKVKQMFKE-ADTDENQ-GTLDFEEFCAFYKMMSTRRDLYLLMLM 219
Cdd:cd16206      1 WLESVFEEADTNKSGFLDEEEAVQLIKQLNPGLSTSRIKQKLKElQKKKDGArGRVSSDEFVELFKELATRPEIYFLLVR 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1952584647  220 YSNHKDQLDTDDLKRFLEVEQKMKGVMKEHCLEIVDKFEPCLENQKQGVLGIDGFTNYMRSP 281
Cdd:cd16206     81 YASNKDYLTVDDLMLFLEAEQGMTGVTKEKCLEIINKYEPSEEGREKGQLGIDGFTRYLLSE 142
PLN02230 PLN02230
phosphoinositide phospholipase C 4
 269-863 3.53e-45

phosphoinositide phospholipase C 4


Pssm-ID: 177875 [Multi-domain]  Cd Length: 598  Bit Score: 174.12  E-value: 3.53e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  269 LGIDGFTNYMRSPagDIFNPEHYKVNQDMTQPMSDYYIASSHNTYLMGDQLMSQSRVDMYAWVLQTGCRCVEVDCWDGPD 348
Cdd:PLN02230    91 LTLDDFNYYLFST--DLNPPIADQVHQNMDAPLSHYFIFTGHNSYLTGNQLSSNCSELPIADALRRGVRVVELDLWPRGT 168

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  349 GEPIVHHGYTLTSKILFRDVIETINKYAFAKSEYPVILSVENHCSVPQQKKMAQGLCEILGDKLdvtSVHE-EDMTQLPS 427
Cdd:PLN02230   169 DDVCVKHGRTLTKEVKLGKCLDSIKANAFAISKYPVIITLEDHLTPKLQFKVAKMITQTFGDML---YYHDsEGCQEFPS 245

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  428 PESLKGKILVKGKK----LPANIS---DDAEEGEVSDEDS-ADEIEDdcklmngdwkAMANRKHVESVAKkkldsllkes 499
Cdd:PLN02230   246 PEELKEKILISTKPpkeyLEANDAkekDNGEKGKDSDEDVwGKEPED----------LISTQSDLDKVTS---------- 305

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  500 kirdredpdsfSVNAIPQagkmcrKADSKKKCSSGSVSTVEKPVSKTEDGTDSGEdPTSNKRHSrsfigsfskrkkktvk 579
Cdd:PLN02230   306 -----------SVNDLNQ------DDEERGSCESDTSCQLQAPEYKRLIAIHAGK-PKGGLRMA---------------- 351

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  580 mkksssLEDDEEdhdhqaaagrttvhmmrsgrQKKTMKLSRALSDlvkytKSVGMYDTDsevmcswqvssysetkthqll 659
Cdd:PLN02230   352 ------LKVDPN--------------------KIRRLSLSEQLLE-----KAVASYGAD--------------------- 379

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  660 qqkpqqFVRMNQQQLSRIYPSSYRVDSSNFNPQPFWNAGCQLVALNYQSEGRVLQLNRAKFSSNGNCGYVLKPK-CMTQG 738
Cdd:PLN02230   380 ------VIRFTQKNFLRIYPKGTRFNSSNYKPQIGWMSGAQMIAFNMQGYGRALWLMEGMFRANGGCGYVKKPDfLMDAG 453

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  739 TLNPTAEDLLTGQPKKQLVLRIISGQQLPKPKDSMLGDRGEIIDPFVEVEIIGLAVDCFKEQTRVVDDNgFNPMWEETLV 818
Cdd:PLN02230   454 PNGQDFYPKDNSCPKKTLKVKVCMGDGWLLDFKKTHFDSYSPPDFFVRVGIAGAPVDEVMEKTKIEYDT-WTPIWNKEFI 532

                          570       580       590       600
                   ....*....|....*....|....*....|....*....|....*.
gi 1952584647  819 FTLYMPNLALVRFLVWDHDPIGR-DFIGQRTLAFTSMMPGYRHVYL 863
Cdd:PLN02230   533 FPLAVPELALLRVEVHEHDINEKdDFGGQTCLPVSEIRQGIHAVPL 578
PI-PLCc cd00137
Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This ...
 295-445 2.15e-41

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: 153.96  E-value: 2.15e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  295 QDMTQPMSDYYIASSHNTYLMGDQL-----MSQSRVDMYAWVLQTGCRCVEVDCWDGPDGEPIVHHGYTLTsKILFRDVI 369
Cdd:cd00137      2 HPDTQPLAHYSIPGTHDTYLTAGQFtikqvWGLTQTEMYRQQLLSGCRCVDIRCWDGKPEEPIIYHGPTFL-DIFLKEVI 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1952584647  370 ETINKYAFAKSEYPVILSVENHCSVP--QQKKMAQGLCEILGDKLdvTSVHEEDMTQLPSPESLKGKILVKGKKLPAN 445
Cdd:cd00137     81 EAIAQFLKKNPPETIIMSLKNEVDSMdsFQAKMAEYCRTIFGDML--LTPPLKPTVPLPSLEDLRGKILLLNKKNGFS 156
EFh_PI-PLCdelta cd16202
EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta ...
 142-281 4.52e-38

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: 139.67  E-value: 4.52e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  142 WLKQTFAEADKNGDGCLSVGEVLQLMHKLNVNLPRQKVKQMFKEADTDENQgTLDFEEFCAFYKMMSTRRDLYLLMLMYS 221
Cdd:cd16202      1 WLKDQFRKADKNGDGKLSFKECKKLLKKLNVKVDKDYAKKLFQEADTSGED-VLDEEEFVQFYNRLTKRPEIEELFKKYS 79

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  222 NHKDQLDTDDLKRFLEVEQKMKGVMKEHCLEIVDKFEPCLENQKQGVLGIDGFTNYMRSP 281
Cdd:cd16202     80 GDDEALTVEELRRFLQEEQKVKDVTLEWAEQLIETYEPSEDLKAQGLMSLDGFTLFLLSP 139
PH_PLC_ELMO1 cd01248
Phospholipase C and Engulfment and cell motility protein 1 pleckstrin homology domain; The ...
 18-123 3.34e-35

Phospholipase C and Engulfment and cell motility protein 1 pleckstrin homology domain; The C-terminal region of ELMO1, the PH domain and Pro-rich sequences, binds the SH3-containing region of DOCK2 forming a intermolecular five-helix bundle allowing for DOCK mediated Rac1 activation. ELMO1, a mammalian homolog of C. elegans CED-12, contains an N-terminal RhoG-binding region, a ELMO domain, a PH domain, and a C-terminal sequence with three PxxP motifs. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). All PLCs, except for PLCzeta, have a PH domain which is for most part N-terminally located, though lipid binding specificity is not conserved between them. In addition PLC gamma contains a split PH domain within its catalytic domain that is separated by 2 SH2 domains and a single SH3 domain. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 269952  Cd Length: 108  Bit Score: 130.13  E-value: 3.34e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647   18 MQSGTQMVKLRGGSKGLVRFYYLDEHKTCIRWRPSRK-NEKAKISIDAIREVCEGKQSEIFQRY-PDGSFDPNCCFSIYY 95
Cdd:cd01248      1 LQQGTLLLKYREGSKPKERTFYLDPDGTRITWESSKKkSEKKSIDISDIKEIRPGKDTDGFKRKkKSNKPKEERCFSIIY 80

                           90       100
                   ....*....|....*....|....*...
gi 1952584647   96 GDHMESLDLVSSNGEEARTWITGLKYLM 123
Cdd:cd01248     81 GSNNKTLDLVAPSEDEANLWVEGLRALL 108
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
 142-282 1.98e-34

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: 128.94  E-value: 1.98e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  142 WLKQTFAEADKNGDGCLSVGEVLQLMHKLNVNLPRQKVKQMFKEADTDeNQGTLDFEEFCAFYKMMSTRRDLYLLMLMY- 220
Cdd:cd15898      1 WLRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVDTN-GDGTLTFDEFEELYKSLTERPELEPIFKKYa 79

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1952584647  221 SNHKDQLDTDDLKRFLEVEQKMKgVMKEHCLEIVDKFEPCLENqkqGVLGIDGFTNYMRSPA 282
Cdd:cd15898     80 GTNRDYMTLEEFIRFLREEQGEN-VSEEECEELIEKYEPEREN---RQLSFEGFTNFLLSPE 137
EFh_PRIP1 cd16222
EF-hand motif found in phospholipase C-related but catalytically inactive protein 1 (PRIP-1); ...
 142-281 2.77e-29

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: 114.57  E-value: 2.77e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  142 WLKQTFAEADKNGDGCLSVGEVLQLMHKLNVNLPRQKVKQMFKEADTDENQGT--LDFEEFCAFYKMMSTRRDLYLLMLM 219
Cdd:cd16222      1 WLSAVFEAADVDGYGIMLEDTAVELIKQLNPGIKEAKIRLKFKEIQKSKEKLTtrVTEEEFCEAYSELCTRPEVYFLLVQ 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1952584647  220 YSNHKDQLDTDDLKRFLEVEQKMKGVMKEHCLEIVDKFEPCLENQKQGVLGIDGFTNYMRSP 281
Cdd:cd16222     81 ISKNKEYLDAKDLMLFLEAEQGMTHITEEMCLDIIRRYEPSQEGRLKGFLGIDGFTQYLLSS 142
EFh_PRIP2 cd16223
EF-hand motif found in phospholipase C-related but catalytically inactive protein 2 (PRIP-2); ...
 142-281 1.20e-27

EF-hand motif found in phospholipase C-related but catalytically inactive protein 2 (PRIP-2); PRIP-2, also termed phospholipase C-L2, or phospholipase C-epsilon-2 (PLC-epsilon-2), or inactive phospholipase C-like protein 2 (PLC-L2), is a novel inositol 1,4,5-trisphosphate (InsP3) binding protein that exhibits a relatively ubiquitous expression. It functions as a novel negative regulator of B-cell receptor (BCR) signaling and immune responses. PRIP-2 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-2 does not have PLC enzymatic activity.


Pssm-ID: 320053 [Multi-domain]  Cd Length: 144  Bit Score: 110.00  E-value: 1.20e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  142 WLKQTFAEADKNGDGCLSVGEVLQLMHKLNVNLPRQKVKQMFKEADTDENQGTLDF--EEFCAFYKMMSTRRDLYLLMLM 219
Cdd:cd16223      1 WLSQMFVEADTDNVGHITLCRAVQFIKNLNPGLKTSKIELKFKELHKSKEKGGTEVtkEEFIEVFHELCTRPEIYFLLVQ 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1952584647  220 YSNHKDQLDTDDLKRFLEVEQKMKGVMKEHCLEIVDKFEPCLENQKQGVLGIDGFTNYMRSP 281
Cdd:cd16223     81 FSSNKEFLDTKDLMMFLEAEQGMAHVTEEISLDIIHKYEPSKEGQEKGWLSLDGFTNYLMSP 142
EFh_PI-PLCdelta4 cd16219
EF-hand motif found in phosphoinositide phospholipase C delta 4 (PI-PLC-delta4); PI-PLC-delta4, ...
 142-281 2.50e-25

EF-hand motif found in phosphoinositide phospholipase C delta 4 (PI-PLC-delta4); PI-PLC-delta4, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 (PLCD4), or phospholipase C-delta-4 (PLC-delta-4), is expressed in various tissues with the highest levels detected selectively in the brain, skeletal muscle, testis and kidney. It plays a significant role in cell growth, cell proliferation, tumorigenesis, and in an early stage of fertilization. PI-PLC-delta4 may function as a key enzyme in the regulation of PtdIns(4,5)P2 levels and Ca2+ metabolism in nuclei in response to growth factors, and its expression may be partially regulated by an increase in cytoplasmic Ca2+. Moreover, PI-PLC-delta4 binds glutamate receptor-interacting protein1 (GRIP1) in testis and is required for calcium mobilization essential for the zona pellucida-induced acrosome reaction in sperm. Overexpression or dysregulated expression of PLCdelta4 may initiate oncogenesis in certain tissues through upregulating erbB1/2 expression, extracellular signal-regulated kinase (ERK) signaling pathway, and proliferation in MCF-7 cells. PI-PLC-delta4 contains an N-terminal pleckstrin homology (PH) domain, 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 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.


Pssm-ID: 320049 [Multi-domain]  Cd Length: 140  Bit Score: 103.00  E-value: 2.50e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  142 WLKQTFAEADKNGDGCLSVGEVLQLMHKLNVNLPRQKVKQMFKEADTDENqGTLDFEEFCAFYKMMSTRRDLYLLMLMYS 221
Cdd:cd16219      1 WIRDWFQKADKNKDGRMNFKEVRDLLKMMNVDMNEEHALRLFQMADKSES-GTLEGEEFVLFYKALTQREDVLKIFQDFS 79

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  222 NHKDQLDTDDLKRFLEVEQKMKGVMKEHCLEIVDKFEPCLENQKQGVLGIDGFTNYMRSP 281
Cdd:cd16219     80 ADGQKLTLLEFVDFLQQEQLERENTEELAMELIDRYEPSDTAKKLHALSIDGFLMYLCSP 139
PLN02223 PLN02223
phosphoinositide phospholipase C
 274-863 5.15e-21

phosphoinositide phospholipase C


Pssm-ID: 165867 [Multi-domain]  Cd Length: 537  Bit Score: 98.94  E-value: 5.15e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  274 FTNYMRSPAGDIFNpehykvNQDMTQPMSDYYIASSHNTYLMGDQLMSQS-RVDMYAWVLQTGCRCVEVDCWdgPDGEP- 351
Cdd:PLN02223    91 FSTELNPPIGDQVR------HHDMHAPLSHYFIHTSLKSYFTGNNVFGKLySIEPIIDALEQGVRVVELDLL--PDGKDg 162

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  352 -IVHHGYTLTSKILFRDVIETINKYAFAKSE-YPVILSVENHCSVPQQKKMAQGLCEILGDKldvtsVHEED----MTQL 425
Cdd:PLN02223   163 iCVRPKWNFEKPLELQECLDAIKEHAFTKCRsYPLIITFKDGLKPDLQSKATQMIDQTFGDM-----VYHEDpqhsLEEF 237

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  426 PSPESLKGKILVKGKKLPANISDDAEEGEVSdedsadeieddcklmngdwkamanrkhvesvakkkldsllkeskirdre 505
Cdd:PLN02223   238 PSPAELQNKILISRRPPKELLYAKADDGGVG------------------------------------------------- 268

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  506 dpdsfsvnaipqagkmcrkadskkkcssgsvstvekpvskTEDGTDSGEDPTsnkrhsrsfigsfskrkkktvkmkksss 585
Cdd:PLN02223   269 ----------------------------------------VRNELEIQEGPA---------------------------- 280

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  586 leddeeDHDHQAAAGRTTVhmmrsgrQKKTMkLSRALSDLVKYTKSVGMYDTDsevmcswqVSSYSETKthqLLQQKPQQ 665
Cdd:PLN02223   281 ------DKNYQSLVGFHAV-------EPRGM-LQKALTGKADDIQQPGWYERD--------IISFTQKK---FLRTRPKK 335

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  666 FVRMnqqqlsrIYPSsyrvdssnFNPQPFWNAGCQLVALNYQSEGRVLQLNRAKFSSNGNCGYVLKPKCM----TQGTLN 741
Cdd:PLN02223   336 KNLL-------INAP--------YKPQRAWMHGAQLIALSRKDDKEKLWLMQGMFRANGGCGYVKKPDFLlnagPSGVFY 400

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  742 PTAEDLLTgqpkKQLVLRIISGQ-----------QLPKPkdsmlgdrgeiiDPFVEVEIIGLAVDcFKEQTRVVDDNGFN 810
Cdd:PLN02223   401 PTENPVVV----KILKVKIYMGDgwivdfkkrigRLSKP------------DLYVRISIAGVPHD-EKIMKTTVKNNEWK 463

                          570       580       590       600       610
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1952584647  811 PMWEETLVFTLYMPNLALVRFLVWDHDPIGRD-FIGQRTLAFTSMMPGYRHVYL 863
Cdd:PLN02223   464 PTWGEEFTFPLTYPDLALISFEVYDYEVSTADaFCGQTCLPVSELIEGIRAVPL 517
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 755-863 5.50e-20

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: 86.39  E-value: 5.50e-20
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647   755 QLVLRIISGQQLPKPkdsmlgDRGEIIDPFVEVEIIGlaVDCFKEQTRVVDDNGfNPMWEETLVFTLYMPNLALVRFLVW 834
Cdd:smart00239    1 TLTVKIISARNLPPK------DKGGKSDPYVKVSLDG--DPKEKKKTKVVKNTL-NPVWNETFEFEVPPPELAELEIEVY 71

                            90       100       110
                    ....*....|....*....|....*....|
gi 1952584647   835 DHDPIGRD-FIGQRTLAFTSMMPGYRHVYL 863
Cdd:smart00239   72 DKDRFGRDdFIGQVTIPLSDLLLGGRHEKL 101
PI-PLCc_GDPD_SF cd08555
Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases ...
 308-414 1.28e-18

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: 85.18  E-value: 1.28e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  308 SSHNTYLMGDQlmsQSRVDMYAWVLQTGCRCVEVDCWDGPDGEPIVHHGYTLT------SKILFRDVIETINKYAFAkSE 381
Cdd:cd08555      2 LSHRGYSQNGQ---ENTLEAFYRALDAGARGLELDVRLTKDGELVVYHGPTLDrttagiLPPTLEEVLELIADYLKN-PD 77

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1952584647  382 YPVILSVENHCSVP----QQKKMAQGLCEILGDKLDV 414
Cdd:cd08555     78 YTIILSLEIKQDSPeydeFLAKVLKELRVYFDYDLRG 114
PH_PLC_delta cd13363
Phospholipase C-delta (PLC-delta) pleckstrin homology (PH) domain; The PLC-delta (PLCdelta) ...
 18-136 1.47e-18

Phospholipase C-delta (PLC-delta) pleckstrin homology (PH) domain; The PLC-delta (PLCdelta) consists of three family members, delta 1, 2, and 3. PLC-delta1 is the most well studied. PLC-delta is activated by high calcium levels generated by other PLC family members, and functions as a calcium amplifier within the cell. PLC-delta consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves, and a C-terminal C2 domain. The PH domain binds PIP2 and promotes activation of the catalytic core as well as tethering the enzyme to the plasma membrane. The C2 domain has been shown to mediate calcium-dependent phospholipid binding as well. The PH and C2 domains operate in concert as a "tether and fix" apparatus necessary for processive catalysis by the enzyme. Its leucine-rich nuclear export signal (NES) in its EF hand motif, as well as a Nuclear localization signal within its linker region allow PLC-delta 1 to actively translocate into and out of the nucleus. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270169  Cd Length: 117  Bit Score: 82.75  E-value: 1.47e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647   18 MQSGTQMVKLRGGSKGLVRFYYLDEHKTCIrWRPSRK---NEKAKISIDAIREVCEGKQSEIFQRYPDgSFDPNCCFSIY 94
Cdd:cd13363      1 LLQGSPLLKVRSRSWKKERFYKLQEDCKTV-WHESKKtrsNSKQTFSIEDIESVREGHQSEGLRKYAE-AFPEDRCFSIV 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1952584647   95 YGDHMESLDLVSSNGEEARTWITGLKYLMAGIsdeDSLSKRQ 136
Cdd:cd13363     79 FKGRRKNLDLIAPSEEEAQRWVRGLEKLIARL---TNMSQRE 117
EFh_ScPlc1p_like cd16207
EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar ...
 158-282 1.68e-18

EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar proteins; This family represents 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 family is protein Plc1p (also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1) encoded by PLC1 genes from Saccharomyces cerevisiae. ScPlc1p 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 ScPlc1p 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 SCPlc1p, 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: 320037 [Multi-domain]  Cd Length: 142  Bit Score: 83.45  E-value: 1.68e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  158 LSVGEVLQLMHKLNVNLPRQKVKQMFKEADTDeNQGTLDFEEFCAFYKMMSTRRDLYLLMLMY-SNHKDQLDTDDLKRFL 236
Cdd:cd16207     19 LDFEDVEKLCRRLHINCSESYLRELFDKADTD-KKGYLNFEEFQEFVKLLKRRKDIKAIFKQLtKPGSDGLTLEEFLKFL 97

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1952584647  237 EVEQKMKgvMKEHCLE-IVDKFEPCLENQKQGVLGIDGFTNYMRSPA 282
Cdd:cd16207     98 RDVQKED--VDRETWEkIFEKFARRIDDSDSLTMTLEGFTSFLLSSY 142
C2 pfam00168
C2 domain;
755-860 2.11e-18

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 81.98  E-value: 2.11e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  755 QLVLRIISGQQLPKPkdsmlgDRGEIIDPFVEVEIIGlavDCFKEQTRVVDdNGFNPMWEETLVFTLYMPNLALVRFLVW 834
Cdd:pfam00168    2 RLTVTVIEAKNLPPK------DGNGTSDPYVKVYLLD---GKQKKKTKVVK-NTLNPVWNETFTFSVPDPENAVLEIEVY 71

                           90       100
                   ....*....|....*....|....*..
gi 1952584647  835 DHDPIGRD-FIGQRTLAFTSMMPGYRH 860
Cdd:pfam00168   72 DYDRFGRDdFIGEVRIPLSELDSGEGL 98
PH_PLC_plant-like cd13365
Plant-like Phospholipase C (PLC) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) was the ...
 11-124 7.53e-17

Plant-like Phospholipase C (PLC) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) was the second class of PLC discovered. PLC-gamma consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves internal to which is a PH domain split by two SH2 domains and a single SH3 domain, and a C-terminal C2 domain. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). This cd contains PLC members from fungi and plants. PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270171  Cd Length: 115  Bit Score: 78.09  E-value: 7.53e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647   11 MERCMSLMQSGTQMVKL--RGGSKglVRFYYLDEHKTCIRWRPSRKNEKAKISIDAIREVCEGKQSEIFQRYPDGSFDpN 88
Cdd:cd13365      3 VIEAITQLKIGSYLLKYgrRGKPH--FRYFWLSPDELTLYWSSPKKGSEKRVRLSSVSRIIPGQRTVVFKRPPPPGLE-E 79

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1952584647   89 CCFSIYYGDHMESLDLVSSNGEEARTWITGLKYLMA 124
Cdd:cd13365     80 HSFSIIYADGERSLDLTCKDRQEFDTWFTGLRYLLS 115
PH_PLC_gamma cd13362
Phospholipase C-gamma (PLC-gamma) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is ...
 21-124 1.60e-16

Phospholipase C-gamma (PLC-gamma) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is activated by receptor and non-receptor tyrosine kinases due to the presence of its SH2 and SH3 domains. There are two main isoforms of PLC-gamma expressed in human specimens, PLC-gamma1 and PLC-gamma2. PLC-gamma consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves internal to which is a PH domain split by two SH2 domains and a single SH3 domain, and a C-terminal C2 domain. Only the first PH domain is present in this hierarchy. PLCs (EC 3.1.4.3) play a role in the initiation of cellular activation, proliferation, differentiation and apoptosis. They are central to inositol lipid signalling pathways, facilitating intracellular Ca2+ release and protein kinase C (PKC) activation. Specificaly, PLCs catalyze the cleavage of phosphatidylinositol-4,5-bisphosphate (PIP2) and result in the release of 1,2-diacylglycerol (DAG) and inositol 1,4,5-triphosphate (IP3). These products trigger the activation of protein kinase C (PKC) and the release of Ca2+ from intracellular stores. There are fourteen kinds of mammalian phospholipase C proteins which are are classified into six isotypes (beta, gamma, delta, epsilon, zeta, eta). PH domains have diverse functions, but in general are involved in targeting proteins to the appropriate cellular location or in the interaction with a binding partner. They share little sequence conservation, but all have a common fold, which is electrostatically polarized. Less than 10% of PH domains bind phosphoinositide phosphates (PIPs) with high affinity and specificity. PH domains are distinguished from other PIP-binding domains by their specific high-affinity binding to PIPs with two vicinal phosphate groups: PtdIns(3,4)P2, PtdIns(4,5)P2 or PtdIns(3,4,5)P3 which results in targeting some PH domain proteins to the plasma membrane. A few display strong specificity in lipid binding. Any specificity is usually determined by loop regions or insertions in the N-terminus of the domain, which are not conserved across all PH domains. PH domains are found in cellular signaling proteins such as serine/threonine kinase, tyrosine kinases, regulators of G-proteins, endocytotic GTPases, adaptors, as well as cytoskeletal associated molecules and in lipid associated enzymes.


Pssm-ID: 270168  Cd Length: 121  Bit Score: 77.32  E-value: 1.60e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647   21 GTQMVKLRGGSKglvrfyylDEHKT-CIR--------WRPSRKNEKAKISIDAIREVCEGKQSEIFQRYPDGS--FDPNC 89
Cdd:cd13362      4 GTVMTKFYQKKR--------PERRTfQVKletrqvvwSRGGGKRAEGAVDIREIKEIRPGKNSKDFERWPDEAkkLDPSC 75

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1952584647   90 CFSIYYGDH--MESLDLVSSNGEEARTWITGLKYLMA 124
Cdd:cd13362     76 CFVILYGTEfrLKTLSVAATSEEECDMWIKGLRYLVE 112
EFh_PI-PLCdelta1 cd16217
EF-hand motif found in phosphoinositide phospholipase C delta 1 (PI-PLC-delta1); PI-PLC-delta1, ...
 142-281 1.05e-14

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: 72.46  E-value: 1.05e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  142 WLKQTFAEADKNGDGCLSVGEVLQLMHKLNVNLPRQKVKQMFKEADTdENQGTLDFEEFCAFYKMMSTRRDLYLLMLMYS 221
Cdd:cd16217      1 WIHSCLRKADKNKDNKMSFKELKDFLKEINIEVDDDYAEKLFKECDK-SKSGFLEGEEIEEFYKLLTKREEIDVIFGEYA 79

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  222 NHKDQLDTDDLKRFLEVEQKMKgVMKEHCLEIVDKFEPCLENQKQGVLGIDGFTNYMRSP 281
Cdd:cd16217     80 KSDGTMSRNNLLNFLQEEQREE-VAPAYALSLIEKYEPDETAKAQRQMTKDGFLMYLLSP 138
EF-hand_like pfam09279
Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...
 203-287 1.72e-14

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: 70.35  E-value: 1.72e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  203 FYKMMSTRRDLYLLMLMYSNHKDQLDTDDLKRFLEVEQKMKGVMKEHCLEIVDKFEPCLENQKQGVLGIDGFTNYMRSPA 282
Cdd:pfam09279    1 FYKMLTQREEIDEIFQEYSGDGQKLSLDELVDFLREEQREEDASPALALSLIERYEPSETAKKQHAMTKDGFLMYLCSPD 80


                   ....*
gi 1952584647  283 GDIFN 287
Cdd:pfam09279   81 GSIFN 85
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 142-208 2.39e-14

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal modulators; most examples in this alignment model have 2 active canonical EF hands. Ca2+ binding induces a conformational change in the EF-hand motif, leading to the activation or inactivation of target proteins. EF-hands tend to occur in pairs or higher copy numbers.


Pssm-ID: 238008 [Multi-domain]  Cd Length: 63  Bit Score: 69.11  E-value: 2.39e-14
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1952584647  142 WLKQTFAEADKNGDGCLSVGEVLQLMHKLNVNLPRQKVKQMFKEADTDENqGTLDFEEFCafyKMMS 208
Cdd:cd00051      1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGD-GKIDFEEFL---ELMA 63
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 756-846 7.97e-14

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: 69.02  E-value: 7.97e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  756 LVLRIISGQQLPKPkdsmlgDRGEIIDPFVEVEIIGLavdcFKEQTRVVDDNgFNPMWEETLVFTLYMPNLALVRFLVWD 835
Cdd:cd00030      1 LRVTVIEARNLPAK------DLNGKSDPYVKVSLGGK----QKFKTKVVKNT-LNPVWNETFEFPVLDPESDTLTVEVWD 69

                           90
                   ....*....|..
gi 1952584647  836 HDPIGRD-FIGQ 846
Cdd:cd00030     70 KDRFSKDdFLGE 81
EF-hand_7 pfam13499
EF-hand domain pair;
140-205 2.59e-12

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 63.43  E-value: 2.59e-12
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1952584647  140 DQWLKQTFAEADKNGDGCLSVGEVLQLMHKL--NVNLPRQKVKQMFKEADTDENqGTLDFEEFCAFYK 205
Cdd:pfam13499    1 EEKLKEAFKLLDSDGDGYLDVEELKKLLRKLeeGEPLSDEEVEELFKEFDLDKD-GRISFEEFLELYS 67
EFh_PI-PLCzeta cd16204
EF-hand motif found in phosphoinositide phospholipase C zeta 1 (PI-PLC-zeta1); PI-PLC-zeta1, ...
 155-280 4.61e-12

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: 65.22  E-value: 4.61e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  155 DGCLSVGEVLQLMHKLNVNLPRQKVKQMFKEADTdENQGTLDFEEFCAFYKMMSTRRDLYLLMLMYSNHKDQLDTDDLKR 234
Cdd:cd16204     16 KGKINLESTLKLLEKLDIPFDYIHVKYIFKKNDS-FKAGNITIEDFRAIYRAIAHRCEIHEIFNTYSENRKILSAPNLVG 94

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1952584647  235 FLEVEQKMKGVMKEHCLEIVDKFEPCLENQKQGVLGIDGFTNYMRS 280
Cdd:cd16204     95 FLKKEQFQDEADETIASELIAKYEPIEEVRKRKQMSFEGFIRYMTS 140
EFh_PI-PLCdelta3 cd16218
EF-hand motif found in phosphoinositide phospholipase C delta 3 (PI-PLC-delta3); PI-PLC-delta3, ...
 142-282 1.43e-11

EF-hand motif found in phosphoinositide phospholipase C delta 3 (PI-PLC-delta3); PI-PLC-delta3, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-3 (PLCD3), phospholipase C-delta-3 (PLC-delta-3), is expressed abundantly in brain, skeletal muscle and heart. PI-PLC-delta3 gene expression is down-regulation by cAMP and calcium. PI-PLC-delta3 acts as anchoring of myosin VI on plasma membrane, and further modulates Myosin IV expression and microvilli formation in enterocytes. It negatively regulates RhoA expression, inhibits RhoA/Rho kinase signaling, and plays an essential role in normal neuronal migration by promoting neuronal outgrowth in the developing brain. Moreover, PI-PLC-delta3 is essential in trophoblasts for placental development. Simultaneous loss of PI-PLC-delta3 may cause placental vascular defects, leading to embryonic lethality. PI-PLC-delta3 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. In addition, PI-PLC-delta3 possesses a classical leucine-rich nuclear export sequence (NES) located in the EF hand motifs, which may be responsible transporting PI-PLC-delta3 from the cell nucleus.


Pssm-ID: 320048 [Multi-domain]  Cd Length: 138  Bit Score: 63.61  E-value: 1.43e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  142 WLKQTFAEADKNGDGCLSVGEVLQLMHKLNVNLPRQKVKQMFKEADTdENQGTLDFEEFCAFYKMMSTRRDLYLLMLMYS 221
Cdd:cd16218      1 WIHEYLRRADLNKDGKMSFEEIKDLLQMINIDLNEQYAYQLFKECDR-SNDDRLEEHEIEEFCRRLMQRPELEEIFHQYS 79

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1952584647  222 NHKDQLDTDDLKRFLEvEQKMKGVMkEHCLEIVDKFEPCLENQKQGVLGIDGFTNYMRSPA 282
Cdd:cd16218     80 GEDCVLSAEELREFLK-DQGEDASL-VHAKELIQTYELNEKAKQHQLMTLDGFTMYMLSKD 138
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
132-203 2.82e-10

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 59.81  E-value: 2.82e-10
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1952584647  132 LSKRQRTRDQWLKQTFAEADKNGDGCLSVGEVLQLMHKLNVnlPRQKVKQMFKEADTDENqGTLDFEEFCAF 203
Cdd:COG5126     60 ESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTALGV--SEEEADELFARLDTDGD-GKISFEEFVAA 128
PH_12 pfam16457
Pleckstrin homology domain;
12-123 1.41e-09

Pleckstrin homology domain;


Pssm-ID: 465123 [Multi-domain]  Cd Length: 128  Bit Score: 57.65  E-value: 1.41e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647   12 ERCMSLMQSGTQMVKLRGGSKGL-VRFYYLDEHKTCIRW---------RPSRKNEKAKISIDAIREVCEGKQSEIF--QR 79
Cdd:pfam16457    3 EQRLNCLLEGAWFPKVRGRRRKKkYRFCRLSPNRKVLHYgdfeekptvDPSLESLPEKIDLSDIKEVVTGKECPHVreSG 82

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1952584647   80 YPDGSFDPNCCFSIYYGDHM-ESLDLVSSNGEEARTWITGLKYLM 123
Cdd:pfam16457   83 KKSKKTSSTLAFSLIYGADEyELLDFVAPSESVAAIWLDGLNMLL 127
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
131-231 5.06e-08

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 53.26  E-value: 5.06e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  131 SLSKRQRTRDQWLKQTFAEADKNGDGCLSVGEVLQLMHKLNVNLPRQKVKQMFKEADTDENqGTLDFEEFCAFYKMMSTR 210
Cdd:COG5126     23 ERDDFEALFRRLWATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDTDGD-GKISADEFRRLLTALGVS 101

                           90       100
                   ....*....|....*....|.
gi 1952584647  211 RDLYLLMLmysnhkDQLDTDD 231
Cdd:COG5126    102 EEEADELF------ARLDTDG 116
EH cd00052
Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and ...
 144-201 1.16e-07

Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and signal transduction. The alignment contains a pair of EF-hand motifs, typically one of them is canonical and binds to Ca2+, while the other may not bind to Ca2+. A hydrophobic binding pocket is formed by residues from both EF-hand motifs. The EH domain binds to proteins containing NPF (class I), [WF]W or SWG (class II), or H[TS]F (class III) sequence motifs.


Pssm-ID: 238009 [Multi-domain]  Cd Length: 67  Bit Score: 50.30  E-value: 1.16e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1952584647  144 KQTFAEADKNGDGCLSVGEVLQLMhkLNVNLPRQKVKQMFKEADTDeNQGTLDFEEFC 201
Cdd:cd00052      2 DQIFRSLDPDGDGLISGDEARPFL--GKSGLPRSVLAQIWDLADTD-KDGKLDKEEFA 56
EFh_PI-PLCbeta cd16200
EF-hand motif found in metazoan phosphoinositide-specific phospholipase C (PI-PLC)-beta ...
 157-281 2.51e-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: 51.86  E-value: 2.51e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  157 CLSVGE----VLQLMHKLNvnLPRQKVKQMFKEAdtdenqgtLDFEEFCAFYKMMSTRRDLY-LLMLMYSNHKDQLDTDD 231
Cdd:cd16200     25 CFSSDKkrkrVLKALKALG--LPDGKNDEIDPED--------FTFEKFFKLYNKLCPRPDIDeIFKELGGKRKPYLTLEQ 94

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1952584647  232 LKRFLEVEQ---KMKGVM-----KEHCLEIVDKFEPCLENQKQGVLGIDGFTNYMRSP 281
Cdd:cd16200     95 LVDFLNEEQrdpRLNEILfpfhtKEQAKKLIDKYEPNEKNKKKGQLTLEGFLRYLMSD 152
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 753-846 6.03e-06

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). 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-I topology and do not bind Ca2+.


Pssm-ID: 175997 [Multi-domain]  Cd Length: 125  Bit Score: 47.24  E-value: 6.03e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  753 KKQLVLRIISGQQLPKPKDSMLGDrgeiidPFVEVEIIGLAVDCFKEQTRVVDdNGFNPMWEETLVFT-LYMPNLaLVRF 831
Cdd:cd04031     15 TSQLIVTVLQARDLPPRDDGSLRN------PYVKVYLLPDRSEKSKRRTKTVK-KTLNPEWNQTFEYSnVRRETL-KERT 86

                           90
                   ....*....|....*....
gi 1952584647  832 L---VWDHDPIG-RDFIGQ 846
Cdd:cd04031     87 LevtVWDYDRDGeNDFLGE 105
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 755-842 6.59e-06

C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. 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. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 175978 [Multi-domain]  Cd Length: 111  Bit Score: 46.42  E-value: 6.59e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  755 QLVLRIISGQQLPkpkdsmlgdrGEIIDPFVEVEIIGLavdcfKEQTRVVDDNGfNPMWEETLVFTLYMPNLAL----VR 830
Cdd:cd04011      5 QVRVRVIEARQLV----------GGNIDPVVKVEVGGQ-----KKYTSVKKGTN-CPFYNEYFFFNFHESPDELfdkiIK 68

                           90
                   ....*....|..
gi 1952584647  831 FLVWDHDPIGRD 842
Cdd:cd04011     69 ISVYDSRSLRSD 80
PTZ00184 PTZ00184
calmodulin; Provisional
 144-210 6.87e-06

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 47.45  E-value: 6.87e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1952584647  144 KQTFAEADKNGDGCLSVGEVLQLMHKLNVNLPRQKVKQMFKEADTDENqGTLDFEEFCAfykMMSTR 210
Cdd:PTZ00184    14 KEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGN-GTIDFPEFLT---LMARK 76
PTZ00184 PTZ00184
calmodulin; Provisional
 143-210 1.39e-05

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 46.68  E-value: 1.39e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1952584647  143 LKQTFAEADKNGDGCLSVGEVLQLMHKLNVNLPRQKVKQMFKEADTDeNQGTLDFEEFCafyKMMSTR 210
Cdd:PTZ00184    86 IKEAFKVFDRDGNGFISAAELRHVMTNLGEKLTDEEVDEMIREADVD-GDGQINYEEFV---KMMMSK 149
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 741-860 1.54e-05

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. There are several classes of Synaptotagmins. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175975 [Multi-domain]  Cd Length: 134  Bit Score: 46.04  E-value: 1.54e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  741 NPTAEdlltgqpkkQLVLRIISGQQLPKPkdsmlgDRGEIIDPFVEVEIIGLAVDCFKEQTRVVDDNgFNPMWEETLVF- 819
Cdd:cd00276     10 LPTAE---------RLTVVVLKARNLPPS------DGKGLSDPYVKVSLLQGGKKLKKKKTSVKKGT-LNPVFNEAFSFd 73

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1952584647  820 --TLYMPNLALVrFLVWDHDPIGRD-FIGQRTLAFTSMMPGYRH 860
Cdd:cd00276     74 vpAEQLEEVSLV-ITVVDKDSVGRNeVIGQVVLGPDSGGEELEH 116
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 758-842 2.40e-05

C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. 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. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175985 [Multi-domain]  Cd Length: 151  Bit Score: 46.09  E-value: 2.40e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  758 LRIISGQQLPKPKDSML--------GDRGEIIDPFVEVEIIGLavdcfKEQTRVVDDNgFNPMWEETLVFTLYMPNLA-L 828
Cdd:cd04018      4 FKIYRAEDLPQMDSGIManvkkaflGEKKELVDPYVEVSFAGQ-----KVKTSVKKNS-YNPEWNEQIVFPEMFPPLCeR 77

                           90
                   ....*....|....
gi 1952584647  829 VRFLVWDHDPIGRD 842
Cdd:cd04018     78 IKIQIRDWDRVGND 91
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
143-257 4.10e-05

Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 45.17  E-value: 4.10e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  143 LKQTFAEADKNGDGCLSVGEVLQLMHKLnvnlprqkVKQMFKEADTDeNQGTLDFEEFCAFYKMMSTRRDLYLLMLMYS- 221
Cdd:COG5126      7 LDRRFDLLDADGDGVLERDDFEALFRRL--------WATLFSEADTD-GDGRISREEFVAGMESLFEATVEPFARAAFDl 77

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1952584647  222 ---NHKDQLDTDDLKRFLEVeqkmKGVMKEHCLEIVDKF 257
Cdd:COG5126     78 ldtDGDGKISADEFRRLLTA----LGVSEEEADELFARL 112
EFh_PI-PLCgamma cd16201
EF-hand motif found in phosphoinositide phospholipase C gamma isozymes (PI-PLC-gamma); ...
 142-241 5.09e-05

EF-hand motif found in phosphoinositide phospholipase C gamma isozymes (PI-PLC-gamma); PI-PLC-gamma 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. They can form a complex with the phosphorylated cytoplasmic domains of the immunoglobulin Ig-alpha and Ig-beta subunits of the B cell receptor (BCR), the membrane-tethered Src family kinase Lyn, phosphorylated spleen tyrosine kinase (Syk), the phosphorylated adaptor protein B-cell linker (BLNK), and activated Bruton's tyrosine kinase (Btk). Like other PI-PLC isozymes, PI-PLC-gamma 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. 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, which is split by two SH2 (Src homology 2) domains, and one SH3 (Src homology 3) domain, are present within this linker. The SH2 and SH3 domains are responsible for the binding of phosphotyrosine-containing sequences and proline-rich sequences, respectively. There are two PI-PLC-gamma isozymes (1-2), both of which are activated by receptor and non-receptor tyrosine kinases due to the presence of SH2 and SH3 domains.


Pssm-ID: 320031 [Multi-domain]  Cd Length: 145  Bit Score: 44.87  E-value: 5.09e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  142 WLKQTFAEADKNGDGCLSVGEVLQLMHKLNVNLPRQKVKQMFKEADTdENQGTLDFEEFCAFY-------KMMSTRRDLY 214
Cdd:cd16201      1 WLRKEFYSMDRTRRETVTLKDLKAFLPRVNCKISTNKLREKFQEVDT-RRRGELGFDDFAQLYhklmfdqKIIEDFFKKY 79

                           90       100
                   ....*....|....*....|....*..
gi 1952584647  215 llmlMYSNHKDQLDTDDLKRFLEVEQK 241
Cdd:cd16201     80 ----SYSSDGQTVTLEDFQRFLLEEQK 102
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 782-851 9.99e-05

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. 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-I topology.


Pssm-ID: 175992 [Multi-domain]  Cd Length: 131  Bit Score: 43.79  E-value: 9.99e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1952584647  782 DPFVEVEIIGLAVDCFKEQTRVVDDNgFNPMWEETLVFTLYMPNLAlvRFL---VWDHDPIGR-DFIGqrTLAF 851
Cdd:cd04026     35 DPYVKLKLIPDPKNETKQKTKTIKKT-LNPVWNETFTFDLKPADKD--RRLsieVWDWDRTTRnDFMG--SLSF 103
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
 143-274 1.87e-04

EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein (ALG-2); The family includes some homologs of mammalian apoptosis-linked gene 2 protein (ALG-2) mainly found in lower eukaryotes, such as a parasitic protist Leishmarua major and a cellular slime mold Dictyostelium discoideum. These homologs contains five EF-hand motifs. Due to the presence of unfavorable residues at the Ca2+-coordinating positions, their non-canonical EF4 and EF5 hands may not bind Ca2+. Two Dictyostelium PEF proteins are the prototypes of this family. They may bind to cytoskeletal proteins and/or signal-transducing proteins localized to detergent-resistant membranes named lipid rafts, and occur as monomers or weak homo- or heterodimers like ALG-2. They can serve as a mediator for Ca2+ signaling-related Dictyostehum programmed cell death (PCD).


Pssm-ID: 320060 [Multi-domain]  Cd Length: 163  Bit Score: 43.74  E-value: 1.87e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  143 LKQTFAEADKNGDGCLSVGEVLQLMHKLNVNLPRQKVKQMFKEADTDENqGTLDFEEFCAFYKmmstrrdlyLLMLMYS- 221
Cdd:cd16185      2 LRQWFRAVDRDRSGSIDVNELQKALAGGGLLFSLATAEKLIRMFDRDGN-GTIDFEEFAALHQ---------FLSNMQNg 71

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1952584647  222 -NHKDQ-----LDTDDLKRFLE------VEQKMKGVMKehcleivdKFEPclenQKQGVLGIDGF 274
Cdd:cd16185     72 fEQRDTsrsgrLDANEVHEALAasgfqlDPPAFQALFR--------KFDP----DRGGSLGFDDY 124
EF-hand_10 pfam14788
EF hand;
158-207 1.94e-04

EF hand;


Pssm-ID: 405477  Cd Length: 50  Bit Score: 40.48  E-value: 1.94e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1952584647  158 LSVGEVLQLMHKLNVNLPRQKVKQMFKEADTDENqGTLDFEEFCAFYKMM 207
Cdd:pfam14788    2 MSFKELKNFLRLINIEVDDSYARKLFQKCDTSQS-GRLEGEEIEEFYKLL 50
PI-PLCc_bacteria_like cd08557
Catalytic domain of bacterial phosphatidylinositol-specific phospholipase C and similar ...
 300-481 2.11e-04

Catalytic domain of bacterial phosphatidylinositol-specific phospholipase C and similar proteins; This subfamily corresponds to the catalytic domain present in bacterial phosphatidylinositol-specific phospholipase C (PI-PLC, EC 4.6.1.13) and their sequence homologs found in eukaryota. Bacterial PI-PLCs participate in Ca2+-independent PI metabolism, hydrolyzing the membrane lipid phosphatidylinositol (PI) to produce phosphorylated myo-inositol and diacylglycerol (DAG). Although their precise physiological function remains unclear, bacterial PI-PLCs may function as virulence factors in some pathogenic bacteria. Bacterial PI-PLCs contain a single TIM-barrel type catalytic domain. Its catalytic mechanism is based on general base and acid catalysis utilizing two well conserved histidines, and consists of two steps, a phosphotransfer and a phosphodiesterase reaction. Eukaryotic homologs in this family are named as phosphatidylinositol-specific phospholipase C X domain containing proteins (PI-PLCXD). They are distinct from the typical eukaryotic phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11), which have a multidomain organization that consists of a PLC catalytic core domain, and various regulatory domains. The catalytic core domain is assembled from two highly conserved X- and Y-regions split by a divergent linker sequence. In contrast, eukaryotic PI-PLCXDs contain a single TIM-barrel type catalytic domain, X domain, which is closely related to that of bacterial PI-PLCs. Although the biological function of eukaryotic PI-PLCXDs still remains unclear, it may be distinct from that of typical eukaryotic PI-PLCs. This family 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: 176500 [Multi-domain]  Cd Length: 271  Bit Score: 45.16  E-value: 2.11e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  300 PMSDYYIASSHNTYlmgDQLMSQSRVDMYAWV----------LQTGCRCVEVDCW-DGPDGEPIVHHGYTLTSKILFRDV 368
Cdd:cd08557      8 PLSQLSIPGTHNSY---AYTIDGNSPIVSKWSktqdlsitdqLDAGVRYLDLRVAyDPDDGDLYVCHGLFLLNGQTLEDV 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  369 IETINkyAFAK---SEyPVILSVENHCSV---PQQKKMAQGLCEILGDKLDVTSVHEEDMtqlpsP---ESLKGKILVkg 439
Cdd:cd08557     85 LNEVK--DFLDahpSE-VVILDLEHEYGGdngEDHDELDALLRDVLGDPLYRPPVRAGGW-----PtlgELRAGKRVL-- 154

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|..
gi 1952584647  440 kklpANISDDAEEGEVSDEDSADeIEDDCKLMNGDWKAMANR 481
Cdd:cd08557    155 ----LFYFGGDDSSGGYDWGSLN-IQDPYANGTDKLESLKAF 191
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 178-207 2.98e-04

EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in pairs. Links between disease states and genes encoding EF-hands, particularly the S100 subclass, are emerging. Each motif consists of a 12 residue loop flanked on either side by a 12 residue alpha-helix. EF-hands undergo a conformational change unpon binding calcium ions.


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 39.28  E-value: 2.98e-04
                            10        20        30
                    ....*....|....*....|....*....|
gi 1952584647   178 KVKQMFKEADTDENqGTLDFEEFCAFYKMM 207
Cdd:smart00054    1 ELKEAFRLFDKDGD-GKIDFEEFKDLLKAL 29
C2_plant_PLD cd04015
C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds ...
 738-845 3.27e-04

C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds in diester glycerophospholipids resulting in the degradation of phospholipids. In vitro PLD transfers phosphatidic acid to primary alcohols. In plants PLD plays a role in germination, seedling growth, phosphatidylinositol metabolism, and changes in phospholipid composition. There is a single Ca(2+)/phospholipid-binding C2 domain in PLD. 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: 175982 [Multi-domain]  Cd Length: 158  Bit Score: 43.06  E-value: 3.27e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  738 GTLNPT---AEDLLTGQPKKQLVLRIIS---GQQLPKPKDSMLGDRGEII--DPFVEVEIIGLAVdcfkEQTRVVDDNGf 809
Cdd:cd04015      7 GTLDVTiyeADNLPNMDMFSEKLRRFFSklvGCSEPTLKRPSSHRHVGKItsDPYATVDLAGARV----ARTRVIENSE- 81

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1952584647  810 NPMWEETlvFTLYMPNLAL-VRFLVWDHDPIGRDFIG 845
Cdd:cd04015     82 NPVWNES--FHIYCAHYAShVEFTVKDNDVVGAQLIG 116
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
 178-207 4.30e-04

EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo calcium dependent conformational changes.


Pssm-ID: 425435 [Multi-domain]  Cd Length: 29  Bit Score: 38.92  E-value: 4.30e-04
                           10        20        30
                   ....*....|....*....|....*....|
gi 1952584647  178 KVKQMFKEADTDENqGTLDFEEFCAFYKMM 207
Cdd:pfam00036    1 ELKEIFRLFDKDGD-GKIDFEEFKELLKKL 29
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
 143-211 4.68e-04

EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein (ALG-2); The family includes some homologs of mammalian apoptosis-linked gene 2 protein (ALG-2) mainly found in lower eukaryotes, such as a parasitic protist Leishmarua major and a cellular slime mold Dictyostelium discoideum. These homologs contains five EF-hand motifs. Due to the presence of unfavorable residues at the Ca2+-coordinating positions, their non-canonical EF4 and EF5 hands may not bind Ca2+. Two Dictyostelium PEF proteins are the prototypes of this family. They may bind to cytoskeletal proteins and/or signal-transducing proteins localized to detergent-resistant membranes named lipid rafts, and occur as monomers or weak homo- or heterodimers like ALG-2. They can serve as a mediator for Ca2+ signaling-related Dictyostehum programmed cell death (PCD).


Pssm-ID: 320060 [Multi-domain]  Cd Length: 163  Bit Score: 42.59  E-value: 4.68e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1952584647  143 LKQTFAEADKNGDGCLSVGEVLQLMHKLNVNLPRQKVKQMFKEADTDeNQGTLDFEEF---CAFykMMSTRR 211
Cdd:cd16185     68 MQNGFEQRDTSRSGRLDANEVHEALAASGFQLDPPAFQALFRKFDPD-RGGSLGFDDYielCIF--LASARN 136
PTZ00183 PTZ00183
centrin; Provisional
 143-200 7.40e-04

centrin; Provisional


Pssm-ID: 185503 [Multi-domain]  Cd Length: 158  Bit Score: 41.98  E-value: 7.40e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1952584647  143 LKQTFAEADKNGDGCLSVGEVLQLMHKLNVNLPRQKVKQMFKEADTDENqGTLDFEEF 200
Cdd:PTZ00183    19 IREAFDLFDTDGSGTIDPKELKVAMRSLGFEPKKEEIKQMIADVDKDGS-GKIDFEEF 75
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 755-866 8.65e-04

C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. 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. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175976 [Multi-domain]  Cd Length: 133  Bit Score: 41.07  E-value: 8.65e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  755 QLVLRIISGQQLPKPKDSMLGDrgeiidPFVEVEII--GLAVDCFKEQTRVVDDNgFNPMWEETLVFTL----YMPNLAL 828
Cdd:cd04009     17 SLRVEILNARNLLPLDSNGSSD------PFVKVELLprHLFPDVPTPKTQVKKKT-LFPLFDESFEFNVppeqCSVEGAL 89

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1952584647  829 VRFLVWDHDPIGR-DFIGQRTLAFTSmMPGYRHVYLEGM 866
Cdd:cd04009     90 LLFTVKDYDLLGSnDFEGEAFLPLND-IPGVEDTSSAQG 127
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 776-845 1.04e-03

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). 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. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176000 [Multi-domain]  Cd Length: 123  Bit Score: 40.73  E-value: 1.04e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1952584647  776 DRGEIIDPFVEVEIIGLAVDCFKEQTRVVDdNGFNPMWEETLVF---TLYMPNLALVRFLVWDHDPIGRDFIG 845
Cdd:cd04035     31 DANGLSDPYVKLNLLPGASKATKLRTKTVH-KTRNPEFNETLTYygiTEEDIQRKTLRLLVLDEDRFGNDFLG 102
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 756-860 1.11e-03

C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176032 [Multi-domain]  Cd Length: 125  Bit Score: 40.78  E-value: 1.11e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  756 LVLRIISGQQLPKPkdsmlgDRGEIIDPFVEVEIigLAVDCFKEQTRVVDDNgFNPMWEETLVF-----------TLYMP 824
Cdd:cd08386     18 LTLKILKAVELPAK------DFSGTSDPFVKIYL--LPDKKHKLETKVKRKN-LNPHWNETFLFegfpyeklqqrVLYLQ 88

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1952584647  825 NLALVRFLvwDHDPIGRDFIGQRTLAFTSMMPGYRH 860
Cdd:cd08386     89 VLDYDRFS--RNDPIGEVSLPLNKVDLTEEQTFWKD 122
EFh_PI-PLCbeta4 cd16211
EF-hand motif found in phosphoinositide phospholipase C beta 4 (PI-PLC-beta4); PI-PLC-beta4, ...
 197-280 1.65e-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: 40.87  E-value: 1.65e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  197 FEEFCAFYKMMSTRRDLYLLML-MYSNHKDQLDTDDLKRFLEVEQK---MKGVM-----KEHCLEIVDKFEPCLENQKQG 267
Cdd:cd16211     59 FEKFYELYHKICPRTDIEELFKkINGDKKDYLTVDQLISFLNEHQRdprLNEILfpfydRKRVMQIIETYEVDEEFKKKE 138

                           90
                   ....*....|...
gi 1952584647  268 VLGIDGFTNYMRS 280
Cdd:cd16211    139 QLSSDGFCRYLMS 151
S-100 cd00213
S-100: S-100 domain, which represents the largest family within the superfamily of proteins ...
 150-203 2.07e-03

S-100: S-100 domain, which represents the largest family within the superfamily of proteins carrying the Ca-binding EF-hand motif. Note that this S-100 hierarchy contains only S-100 EF-hand domains, other EF-hands have been modeled separately. S100 proteins are expressed exclusively in vertebrates, and are implicated in intracellular and extracellular regulatory activities. Intracellularly, S100 proteins act as Ca-signaling or Ca-buffering proteins. The most unusual characteristic of certain S100 proteins is their occurrence in extracellular space, where they act in a cytokine-like manner through RAGE, the receptor for advanced glycation products. Structural data suggest that many S100 members exist within cells as homo- or heterodimers and even oligomers; oligomerization contributes to their functional diversification. Upon binding calcium, most S100 proteins change conformation to a more open structure exposing a hydrophobic cleft. This hydrophobic surface represents the interaction site of S100 proteins with their target proteins. There is experimental evidence showing that many S100 proteins have multiple binding partners with diverse mode of interaction with different targets. In addition to S100 proteins (such as S100A1,-3,-4,-6,-7,-10,-11,and -13), this group includes the ''fused'' gene family, a group of calcium binding S100-related proteins. The ''fused'' gene family includes multifunctional epidermal differentiation proteins - profilaggrin, trichohyalin, repetin, hornerin, and cornulin; functionally these proteins are associated with keratin intermediate filaments and partially crosslinked to the cell envelope. These ''fused'' gene proteins contain N-terminal sequence with two Ca-binding EF-hands motif, which may be associated with calcium signaling in epidermal cells and autoprocessing in a calcium-dependent manner. In contrast to S100 proteins, "fused" gene family proteins contain an extraordinary high number of almost perfect peptide repeats with regular array of polar and charged residues similar to many known cell envelope proteins.


Pssm-ID: 238131 [Multi-domain]  Cd Length: 88  Bit Score: 38.62  E-value: 2.07e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  150 ADKNGDGC-LSVGEVLQLMHK-LNVNLPRQK----VKQMFKEADTDENqGTLDFEEFCAF 203
Cdd:cd00213     18 SGKEGDKDtLSKKELKELLETeLPNFLKNQKdpeaVDKIMKDLDVNKD-GKVDFQEFLVL 76
C2_putative_Elicitor-responsive_gene cd04049
C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive ...
 781-849 4.20e-03

C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive proteins are triggered in response to specific elicitor molecules such as glycolproteins, peptides, carbohydrates and lipids. A host of defensive responses are also triggered resulting in localized cell death. Antimicrobial secondary metabolites, such as phytoalexins, or defense-related proteins, including pathogenesis-related (PR) proteins are also produced. There is a single C2 domain present here. 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 have a type-II topology.


Pssm-ID: 176014 [Multi-domain]  Cd Length: 124  Bit Score: 38.85  E-value: 4.20e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1952584647  781 IDPFVEVEiiglavdcFKEQTR---VVDDNGFNPMWEETLVFTLYMPNLALVRFL---VWDHDPI-GRDFIGQRTL 849
Cdd:cd04049     22 IDPYVIIQ--------CRTQERkskVAKGDGRNPEWNEKFKFTVEYPGWGGDTKLilrIMDKDNFsDDDFIGEATI 89
EH smart00027
Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe ...
 145-202 5.07e-03

Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe (NPF) sequences.


Pssm-ID: 197477 [Multi-domain]  Cd Length: 96  Bit Score: 38.03  E-value: 5.07e-03
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*...
gi 1952584647   145 QTFAEADKNGDGCLSVGEVLQLMhkLNVNLPRQKVKQMFKEADTDeNQGTLDFEEFCA 202
Cdd:smart00027   14 QIFRSLDKNQDGTVTGAQAKPIL--LKSGLPQTLLAKIWNLADID-NDGELDKDEFAL 68
EF-hand_8 pfam13833
EF-hand domain pair;
154-206 5.53e-03

EF-hand domain pair;


Pssm-ID: 404678 [Multi-domain]  Cd Length: 54  Bit Score: 36.52  E-value: 5.53e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1952584647  154 GDGCLSVGEVLQLMHKLNVN-LPRQKVKQMFKEADTDeNQGTLDFEEFCAFYKM 206
Cdd:pfam13833    1 EKGVITREELKRALALLGLKdLSEDEVDILFREFDTD-GDGYISFDEFCVLLER 53
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
 798-845 5.70e-03

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. 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. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175987 [Multi-domain]  Cd Length: 162  Bit Score: 39.23  E-value: 5.70e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1952584647  798 KEQTRVVDDNGfNPMWEETLVFTLYMP---NLALVRFLVWDHDPIGR-DFIG 845
Cdd:cd04020     65 KQKTPVVKKSV-NPVWNHTFVYDGVSPedlSQACLELTVWDHDKLSSnDFLG 115
C2_Munc13_fungal cd04043
C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are ...
 758-849 7.47e-03

C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. 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. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176008 [Multi-domain]  Cd Length: 126  Bit Score: 38.40  E-value: 7.47e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1952584647  758 LRIISGQQLPKPKDSmlgdrgEIIDPFVEVEIIGLAVDCFKeqTRVVDDNgFNPMWEETLVFTLYMPNLALVRFLVWDHD 837
Cdd:cd04043      5 IRIVRAENLKADSSN------GLSDPYVTLVDTNGKRRIAK--TRTIYDT-LNPRWDEEFELEVPAGEPLWISATVWDRS 75

                           90
                   ....*....|...
gi 1952584647  838 PIGR-DFIGQRTL 849
Cdd:cd04043     76 FVGKhDLCGRASL 88
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
 143-170 8.79e-03

EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering/transport proteins. The first group is the largest and includes the most well-known members of the family such as calmodulin, troponin C and S100B. These proteins typically undergo a calcium-dependent conformational change which opens a target binding site. The latter group is represented by calbindin D9k and do not undergo calcium dependent conformational changes.


Pssm-ID: 425435 [Multi-domain]  Cd Length: 29  Bit Score: 35.07  E-value: 8.79e-03
                           10        20
                   ....*....|....*....|....*...
gi 1952584647  143 LKQTFAEADKNGDGCLSVGEVLQLMHKL 170
Cdd:pfam00036    2 LKEIFRLFDKDGDGKIDFEEFKELLKKL 29
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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