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Conserved domains on  [gi|732170452|ref|NP_001289942|]
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1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-2 isoform 3 [Homo sapiens]

Protein Classification

PLC family C2 domain-containing protein; PLC-eta family PH domain-containing protein( domain architecture ID 11598620)

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)| PLC-eta family PH (pleckstrin homology) domain-containing protein similar to PH region of Homo sapiens inactive phospholipase C-like protein 2 (PLCL2) that may play an role in the regulation of Ins(1,4,5)P3 around the endoplasmic reticulum

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PI-PLCc_eta2 cd08633
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...
 345-747 8.76e-178

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: 517.29  E-value: 8.76e-178
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  345 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 424
Cdd:cd08633     1 NQDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  425 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSSVSSEDATTLPSPQMLKGKILVKGKklpanisedaeeg 504
Cdd:cd08633    81 KYAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLDLSSVISNDCTRLPSPEILKGKILVKGK------------- 147

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  505 evsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesge 584
Cdd:cd08633       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  585 dagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmKLSRALSDLVKYTKSVATHDIEME 664
Cdd:cd08633   148 --------------------------------------------------------KLSRALSDLVKYTKSVRVHDIETE 171

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  665 AASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKF 744
Cdd:cd08633   172 ATSSWQVSSFSETKAHQILQQKPAQYLRFNQRQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKF 251


                  ...
gi 732170452  745 SAN 747
Cdd:cd08633   252 SAN 254
EFh_PI-PLCeta2 cd16221
EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also ...
 193-333 7.17e-100

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: 309.94  E-value: 7.17e-100
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  193 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDHQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 272
Cdd:cd16221     1 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEADTDDNQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 732170452  273 NHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSPA 333
Cdd:cd16221    81 NHKDHLDTNDLQRFLEVEQKMAGVTREHCLEIISQFEPCSENKQNGALGIDGFTNYMRSPA 141
PH_PLC_eta cd13364
Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of ...
 69-175 1.28e-54

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: 184.79  E-value: 1.28e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452   69 MQEGMQMVKLRGGSKGLVRFYYLDEHRSCIRWRPSRKN-EKAKISIDSIQEVSEGRQSEVFQRYP-DGSFDPNCCFSIYH 146
Cdd:cd13364     1 MQEGSELVKVRSNSRQYRRFFYLDEDKSSIRWKPSKKKsEKAKIPISSIREVREGKTTDIFRSCDiSGDFPEECCFSIIY 80

                          90       100
                  ....*....|....*....|....*....
gi 732170452  147 GSHRESLDLVSTSSEVARTWVTGLRYLMA 175
Cdd:cd13364    81 GEEYETLDLVASSPDEANIWITGLRYLMS 109
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 777-902 1.27e-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: 176.96  E-value: 1.27e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  777 KKQLVLRIISGQQLPKPRDsmlgDRGEIIDPFVEVEIIGLPV-DCSREQTRVVDDNGFNPTWEETLVFMVHMPEIALVRF 855
Cdd:cd00275     1 PLTLTIKIISGQQLPKPKG----DKGSIVDPYVEVEIHGLPAdDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRF 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 732170452  856 LVWDHDPIGRDFIGQRTLAFSSMMPGYRHVYL-----EGMEEASIFVHVAVS 902
Cdd:cd00275    77 VVYDEDSGDDDFLGQACLPLDSLRQGYRHVPLldskgEPLELSTLFVHIDIT 128
 
Name Accession Description Interval E-value
PI-PLCc_eta2 cd08633
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...
 345-747 8.76e-178

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: 517.29  E-value: 8.76e-178
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  345 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 424
Cdd:cd08633     1 NQDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  425 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSSVSSEDATTLPSPQMLKGKILVKGKklpanisedaeeg 504
Cdd:cd08633    81 KYAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLDLSSVISNDCTRLPSPEILKGKILVKGK------------- 147

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  505 evsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesge 584
Cdd:cd08633       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  585 dagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmKLSRALSDLVKYTKSVATHDIEME 664
Cdd:cd08633   148 --------------------------------------------------------KLSRALSDLVKYTKSVRVHDIETE 171

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  665 AASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKF 744
Cdd:cd08633   172 ATSSWQVSSFSETKAHQILQQKPAQYLRFNQRQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKF 251


                  ...
gi 732170452  745 SAN 747
Cdd:cd08633   252 SAN 254
EFh_PI-PLCeta2 cd16221
EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also ...
 193-333 7.17e-100

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: 309.94  E-value: 7.17e-100
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  193 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDHQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 272
Cdd:cd16221     1 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEADTDDNQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 732170452  273 NHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSPA 333
Cdd:cd16221    81 NHKDHLDTNDLQRFLEVEQKMAGVTREHCLEIISQFEPCSENKQNGALGIDGFTNYMRSPA 141
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
 348-490 9.45e-85

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: 269.37  E-value: 9.45e-85
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452   348 MTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINKYA 427
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 732170452   428 FIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLdLSSVSSEDATTLPSPQMLKGKILVKG 490
Cdd:pfam00388   81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDML-YTPPLDDDLTELPSPEDLKGKILIKG 142
PLN02952 PLN02952
phosphoinositide phospholipase C
 262-887 1.39e-68

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 241.06  E-value: 1.39e-68
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  262 RDLYLLMLTYSNHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEpcpeNK-------SKGLLGIDGFTNYTRSPag 334
Cdd:PLN02952   38 DDVKDVFCKFSVGGGHMGADQLRRFLVLHQDELDCTLAEAQRIVEEVI----NRrhhvtryTRHGLNLDDFFHFLLYD-- 111

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  335 DIFNPEHHHVHQDMTQPLSHYFITSSHNTYLVGDQLMSQ-SRVDMYAwVLQAGCRCVEVDCWDGPDGEPI-VHHGYTLTS 412
Cdd:PLN02952  112 DLNGPITPQVHHDMTAPLSHYFIYTGHNSYLTGNQLSSDcSEVPIVK-ALQRGVRVIELDLWPGSTKDEIlVLHGRTLTT 190

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  413 KILFKDVIETINKYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSsvSSEDATTLPSPQMLKGKILVKGKK 492
Cdd:PLN02952  191 PVPLIKCLKSIRDYAFSSSPYPVIITLEDHLTPDLQAKVAEMATQIFGQMLYYP--ESDSLVQFPSPESLKHRIIISTKP 268

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  493 lPANISEDaeegevsdedsadeidddckllNGDASTNRKrventakrkldslikeskirdcedpnnfsvSTLSPSGKlgR 572
Cdd:PLN02952  269 -PKEYLES----------------------SGPIVIKKK------------------------------NNVSPSGR--N 293

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  573 KSKAEEDVESGEDAGASrrngrlvvgsfsrrkkkgsklkkAASVEEGDEGQDSPGGQSRGATRQKKTM-----KLSRALS 647
Cdd:PLN02952  294 SSEETEEAQTLESMLFE-----------------------QEADSRSDSDQDDNKSGELQKPAYKRLItihagKPKGTLK 350

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  648 DLVKYtksvathdiemeAASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVA 727
Cdd:PLN02952  351 DAMKV------------AVDKVRRLSLSEQELEKAATTNGQDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIA 418

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  728 LNYQSEGRMLQLNRAKFSANGGCGYVLKPGCMCQGVFNPNSEDP---LPgqLKKQLVLRIISGQQLPKPRDSMLGDRGEI 804
Cdd:PLN02952  419 FNMQGYGKSLWLMHGMFRANGGCGYLKKPDFLMKKGFHDEVFDPkkkLP--VKKTLKVKVYLGDGWRLDFSHTHFDSYSP 496

                         570       580       590       600       610       620       630       640
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  805 IDPFVEVEIIGLPVDCSREQTRVVDDNgFNPTWEETLVFMVHMPEIALVRFLVWDHDPIGR-DFIGQRTLAFSSMMPGYR 883
Cdd:PLN02952  497 PDFYTKMYIVGVPADNAKKKTKIIEDN-WYPAWNEEFSFPLTVPELALLRIEVREYDMSEKdDFGGQTCLPVSELRPGIR 575


                  ....
gi 732170452  884 HVYL 887
Cdd:PLN02952  576 SVPL 579
PLCXc smart00148
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...
 348-491 2.61e-63

Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. These enzymes contain 2 regions (X and Y) which together form a TIM barrel-like structure containing the active site residues. Phospholipase C enzymes (PI-PLC) act as signal transducers that generate two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. The bacterial enzyme appears to be a homologue of the mammalian PLCs.


Pssm-ID: 197543 [Multi-domain]  Cd Length: 143  Bit Score: 210.60  E-value: 2.61e-63
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452    348 MTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINKYA 427
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 732170452    428 FIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLdLSSVSSEDATTLPSPQMLKGKILVKGK 491
Cdd:smart00148   81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDML-YTPPLTSSLEVLPSPEQLRGKILLKVR 143
PH_PLC_eta cd13364
Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of ...
 69-175 1.28e-54

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: 184.79  E-value: 1.28e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452   69 MQEGMQMVKLRGGSKGLVRFYYLDEHRSCIRWRPSRKN-EKAKISIDSIQEVSEGRQSEVFQRYP-DGSFDPNCCFSIYH 146
Cdd:cd13364     1 MQEGSELVKVRSNSRQYRRFFYLDEDKSSIRWKPSKKKsEKAKIPISSIREVREGKTTDIFRSCDiSGDFPEECCFSIIY 80

                          90       100
                  ....*....|....*....|....*....
gi 732170452  147 GSHRESLDLVSTSSEVARTWVTGLRYLMA 175
Cdd:cd13364    81 GEEYETLDLVASSPDEANIWITGLRYLMS 109
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 777-902 1.27e-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: 176.96  E-value: 1.27e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  777 KKQLVLRIISGQQLPKPRDsmlgDRGEIIDPFVEVEIIGLPV-DCSREQTRVVDDNGFNPTWEETLVFMVHMPEIALVRF 855
Cdd:cd00275     1 PLTLTIKIISGQQLPKPKG----DKGSIVDPYVEVEIHGLPAdDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRF 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 732170452  856 LVWDHDPIGRDFIGQRTLAFSSMMPGYRHVYL-----EGMEEASIFVHVAVS 902
Cdd:cd00275    77 VVYDEDSGDDDFLGQACLPLDSLRQGYRHVPLldskgEPLELSTLFVHIDIT 128
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 779-887 7.85e-22

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: 91.01  E-value: 7.85e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452    779 QLVLRIISGQQLPKPrdsmlgDRGEIIDPFVEVEIIGLPVdcSREQTRVVDDNGfNPTWEETLVFMVHMPEIALVRFLVW 858
Cdd:smart00239    1 TLTVKIISARNLPPK------DKGGKSDPYVKVSLDGDPK--EKKKTKVVKNTL-NPVWNETFEFEVPPPELAELEIEVY 71

                            90       100       110
                    ....*....|....*....|....*....|
gi 732170452    859 DHDPIGRD-FIGQRTLAFSSMMPGYRHVYL 887
Cdd:smart00239   72 DKDRFGRDdFIGQVTIPLSDLLLGGRHEKL 101
C2 pfam00168
C2 domain;
779-884 5.18e-20

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 85.83  E-value: 5.18e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452   779 QLVLRIISGQQLPKPrdsmlgDRGEIIDPFVEVEIIGlpvDCSREQTRVVDdNGFNPTWEETLVFMVHMPEIALVRFLVW 858
Cdd:pfam00168    2 RLTVTVIEAKNLPPK------DGNGTSDPYVKVYLLD---GKQKKKTKVVK-NTLNPVWNETFTFSVPDPENAVLEIEVY 71

                           90       100
                   ....*....|....*....|....*..
gi 732170452   859 DHDPIGRD-FIGQRTLAFSSMMPGYRH 884
Cdd:pfam00168   72 DYDRFGRDdFIGEVRIPLSELDSGEGL 98
EF-hand_like pfam09279
Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...
 254-338 2.22e-13

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: 66.50  E-value: 2.22e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452   254 FYKMMSTRRDLYLLMLTYSNHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSPA 333
Cdd:pfam09279    1 FYKMLTQREEIDEIFQEYSGDGQKLSLDELVDFLREEQREEDASPALALSLIERYEPSETAKKQHAMTKDGFLMYLCSPD 80


                   ....*
gi 732170452   334 GDIFN 338
Cdd:pfam09279   81 GSIFN 85
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
183-254 2.20e-10

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 59.42  E-value: 2.20e-10
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 732170452  183 LARRQRTRDQWLKQTFDEADKNGDGSLSIGEVLQLLHKLNVnlPRQRVKQMFREADTdDHQGTLGFEEFCAF 254
Cdd:COG5126    60 ESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTALGV--SEEEADELFARLDT-DGDGKISFEEFVAA 128
PH_12 pfam16457
Pleckstrin homology domain;
63-174 9.64e-10

Pleckstrin homology domain;


Pssm-ID: 465123 [Multi-domain]  Cd Length: 128  Bit Score: 57.65  E-value: 9.64e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452    63 ERCMGAMQEGMQMVKLRGGSKGL-VRFYYLDEHRSCIRW---------RPSRKNEKAKISIDSIQEVSEGRQSEVF--QR 130
Cdd:pfam16457    3 EQRLNCLLEGAWFPKVRGRRRKKkYRFCRLSPNRKVLHYgdfeekptvDPSLESLPEKIDLSDIKEVVTGKECPHVreSG 82

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 732170452   131 YPDGSFDPNCCFSIYHGSH-RESLDLVSTSSEVARTWVTGLRYLM 174
Cdd:pfam16457   83 KKSKKTSSTLAFSLIYGADeYELLDFVAPSESVAAIWLDGLNMLL 127
PTZ00184 PTZ00184
calmodulin; Provisional
 183-261 4.16e-06

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 47.45  E-value: 4.16e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  183 LARRQRTRD--QWLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDhQGTLGFEEFCafyKMMST 260
Cdd:PTZ00184   73 MARKMKDTDseEEIKEAFKVFDRDGNGFISAAELRHVMTNLGEKLTDEEVDEMIREADVDG-DGQINYEEFV---KMMMS 148


                  .
gi 732170452  261 R 261
Cdd:PTZ00184  149 K 149
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 230-258 3.32e-03

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: 35.82  E-value: 3.32e-03
                            10        20
                    ....*....|....*....|....*....
gi 732170452    230 VKQMFREADTdDHQGTLGFEEFCAFYKMM 258
Cdd:smart00054    2 LKEAFRLFDK-DGDGKIDFEEFKDLLKAL 29
 
Name Accession Description Interval E-value
PI-PLCc_eta2 cd08633
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...
 345-747 8.76e-178

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: 517.29  E-value: 8.76e-178
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  345 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 424
Cdd:cd08633     1 NQDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  425 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSSVSSEDATTLPSPQMLKGKILVKGKklpanisedaeeg 504
Cdd:cd08633    81 KYAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLDLSSVISNDCTRLPSPEILKGKILVKGK------------- 147

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  505 evsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesge 584
Cdd:cd08633       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  585 dagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmKLSRALSDLVKYTKSVATHDIEME 664
Cdd:cd08633   148 --------------------------------------------------------KLSRALSDLVKYTKSVRVHDIETE 171

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  665 AASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKF 744
Cdd:cd08633   172 ATSSWQVSSFSETKAHQILQQKPAQYLRFNQRQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKF 251


                  ...
gi 732170452  745 SAN 747
Cdd:cd08633   252 SAN 254
PI-PLCc_eta cd08594
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family ...
 345-747 2.28e-148

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: 440.39  E-value: 2.28e-148
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  345 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 424
Cdd:cd08594     1 NQDMTQPLSHYFIASSHNTYLTGDQLLSQSRVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKILFRDVIETIN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  425 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSSVSSEDATTLPSPQMLKGKILVKGKKlpanisedaeeg 504
Cdd:cd08594    81 KYAFIKNEYPVILSIENHCSVQQQKKMAQYLKEILGDKLDLSSVISGDSKQLPSPQSLKGKILIKGKK------------ 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  505 evsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesge 584
Cdd:cd08594       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  585 dagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmklsralsdlvkytksvathdieme 664
Cdd:cd08594       --------------------------------------------------------------------------------

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  665 aassWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKF 744
Cdd:cd08594   149 ----WQVSSFSETRAHQIVQQKAAQFLRFNQRQLSRIYPSAYRIDSSNFNPQPYWNAGCQLVALNYQTEGRMLQLNRAKF 224


                  ...
gi 732170452  745 SAN 747
Cdd:cd08594   225 RAN 227
PI-PLCc_eta1 cd08632
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily ...
 345-747 5.17e-135

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: 406.72  E-value: 5.17e-135
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  345 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 424
Cdd:cd08632     1 NQDMDQPLCNYFIASSHNTYLTGDQLLSQSKVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKITFRDVIETIN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  425 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSSVSSEDATTLPSPQMLKGKILVKGKklpanisedaeeg 504
Cdd:cd08632    81 KYAFVKNEFPVILSIENHCSIQQQKKIAQYLKEIFGDKLDLSSVLTGDPKQLPSPQLLKGKILVKGK------------- 147

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  505 evsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesge 584
Cdd:cd08632       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  585 dagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmKLSRALSDLVKYTKSVATHDIeME 664
Cdd:cd08632   148 --------------------------------------------------------KLCRDLSDLVVYTNSVAAQDI-VD 170

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  665 AASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKF 744
Cdd:cd08632   171 DGSTGNVLSFSETRAHQLVQQKAEQFMTYNQKQLTRIYPSAYRIDSSNFNPLPYWNVGCQLVALNYQSEGRMMQLNRAKF 250


                  ...
gi 732170452  745 SAN 747
Cdd:cd08632   251 MVN 253
PI-PLCc_eukaryota cd08558
Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; ...
 345-747 3.20e-131

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: 395.67  E-value: 3.20e-131
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  345 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 424
Cdd:cd08558     1 YQDMTQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGHTLTSKILFKDVIEAIK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  425 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSSVSSEDaTTLPSPQMLKGKILVKGKKlpanisedaeeg 504
Cdd:cd08558    81 EYAFVTSPYPVILSLENHCSLEQQKKMAQILKEIFGDKLLTPPLDENP-VQLPSPEQLKGKILIKGKK------------ 147

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  505 evsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesge 584
Cdd:cd08558       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  585 dagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmklsralsdlvkytksvathdieme 664
Cdd:cd08558       --------------------------------------------------------------------------------

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  665 aassWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKF 744
Cdd:cd08558   148 ----YHMSSFSETKALKLLKESPEEFVKYNKRQLSRVYPKGTRVDSSNYNPQPFWNAGCQMVALNYQTPDLPMQLNQGKF 223


                  ...
gi 732170452  745 SAN 747
Cdd:cd08558   224 EQN 226
PI-PLCc_delta cd08593
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily ...
 345-747 9.67e-120

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: 367.05  E-value: 9.67e-120
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  345 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 424
Cdd:cd08593     1 YQDMTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDGPDGEPIIYHGHTLTSKILFKDVIQAIR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  425 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLdLSSVSSEDATTLPSPQMLKGKILVKGKKLpanisedaeeg 504
Cdd:cd08593    81 EYAFKVSPYPVILSLENHCSVEQQKVMAQHLKSILGDKL-LTQPLDGVLTALPSPEELKGKILVKGKKL----------- 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  505 evsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesge 584
Cdd:cd08593       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  585 dagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmKLSRALSDLVKYTKSVATHDIE-- 662
Cdd:cd08593   149 --------------------------------------------------------KLAKELSDLVIYCKSVHFKSFEhs 172

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  663 MEAASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRA 742
Cdd:cd08593   173 KENYHFYEMSSFSESKALKLAQESGNEFVRHNKRQLSRIYPAGLRTDSSNYDPQEMWNVGCQIVALNFQTPGEEMDLNDG 252


                  ....*
gi 732170452  743 KFSAN 747
Cdd:cd08593   253 LFRQN 257
PI-PLCc_PRIP_metazoa cd08597
Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This ...
 345-747 4.00e-100

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: 315.13  E-value: 4.00e-100
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  345 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 424
Cdd:cd08597     1 CQDMTQPLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDGPNGEPVIYHGHTLTSKISFRSVIEAIN 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  425 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSSVsSEDATTLPSPQMLKGKILVKGKKLpanisedaeeg 504
Cdd:cd08597    81 EYAFVASEYPLILCIENHCSEKQQLVMAQYLKEIFGDKLYTEPP-NEGESYLPSPHDLKGKIIIKGKKL----------- 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  505 evsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesge 584
Cdd:cd08597       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  585 dagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkKTMKLSRALSDLVKYTKSVATHDIEME 664
Cdd:cd08597   149 -----------------------------------------------------KRRKLCKELSDLVSLCKSVRFQDFPTS 175

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  665 AASS--WQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRA 742
Cdd:cd08597   176 AQNQkyWEVCSFSENLARRLANEFPEDFVNYNKKFLSRVYPSPMRVDSSNYNPQDFWNCGCQIVAMNYQTPGLMMDLNTG 255


                  ....*
gi 732170452  743 KFSAN 747
Cdd:cd08597   256 KFLEN 260
EFh_PI-PLCeta2 cd16221
EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also ...
 193-333 7.17e-100

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: 309.94  E-value: 7.17e-100
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  193 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDHQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 272
Cdd:cd16221     1 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEADTDDNQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 732170452  273 NHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSPA 333
Cdd:cd16221    81 NHKDHLDTNDLQRFLEVEQKMAGVTREHCLEIISQFEPCSENKQNGALGIDGFTNYMRSPA 141
EFh_PI-PLCeta cd16205
EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes ...
 193-333 3.09e-96

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: 300.07  E-value: 3.09e-96
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  193 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDHQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 272
Cdd:cd16205     1 WLKQTFEEADKNGDGLLSIGEILQLMHKLNVNLPRRKVRQMFKEADTDDNQGTLDFEEFCAFYKMMSTRRELYLLLLSYS 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 732170452  273 NHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSPA 333
Cdd:cd16205    81 NKKDYLTLEDLARFLEVEQKMTNVTLEYCLDIIEKFEPSEENKKNGLLGIDGFTNYMRSPA 141
PI-PLCc_gamma cd08592
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...
 346-747 9.45e-95

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: 299.73  E-value: 9.45e-95
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  346 QDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 425
Cdd:cd08592     2 QDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGPDGMPIIYHGHTLTSKIKFMDVLKTIKE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  426 YAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLdLSSVSSEDATTLPSPQMLKGKILVKGKKLpanisedaeege 505
Cdd:cd08592    82 HAFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDML-LTQPVDRNADQLPSPNQLKRKIIIKHKKL------------ 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  506 vsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesged 585
Cdd:cd08592       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  586 agasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmklsralsdlvkYTksvathdiEMea 665
Cdd:cd08592   149 ------------------------------------------------------------------FY--------EM-- 152

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  666 asswqvSSFSETKAHQIL-QQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKF 744
Cdd:cd08592   153 ------SSFPETKAEKYLnRQKGKIFLKYNRRQLSRVYPKGQRVDSSNYDPVPMWNCGSQMVALNFQTPDKPMQLNQALF 226


                  ...
gi 732170452  745 SAN 747
Cdd:cd08592   227 MLN 229
PI-PLCc_beta cd08591
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ...
 345-747 1.16e-94

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: 300.41  E-value: 1.16e-94
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  345 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDG--PDGEPIVHHGYTLTSKILFKDVIET 422
Cdd:cd08591     1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGkgEDEEPIITHGKTMCTEILFKDVIEA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  423 INKYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKL---DLSSVSSEDATTLPSPQMLKGKILVKGKKlpanise 499
Cdd:cd08591    81 IAETAFKTSEYPVILSFENHCSSKQQAKMAEYCREIFGDLLltePLEKYPLEPGVPLPSPNDLKRKILIKNKK------- 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  500 daeegevsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeed 579
Cdd:cd08591       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  580 vesgedagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmklsraLSDLVKYTKSV--A 657
Cdd:cd08591   154 ------------------------------------------------------------------LSSLVNYIQPVkfQ 167

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  658 THDIEMEAASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRML 737
Cdd:cd08591   168 GFEVAEKRNKHYEMSSFNESKGLGYLKKSPIEFVNYNKRQLSRIYPKGTRVDSSNYMPQIFWNAGCQMVALNFQTPDLPM 247

                         410
                  ....*....|
gi 732170452  738 QLNRAKFSAN 747
Cdd:cd08591   248 QLNQGKFEYN 257
PI-PLCc_delta4 cd08631
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily ...
 345-747 6.72e-94

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: 298.78  E-value: 6.72e-94
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  345 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 424
Cdd:cd08631     1 YQDMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDGPNGEPIVYHGHTFTSKILFKDVVAAVA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  425 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSSVSSEDATTLPSPQMLKGKILVKGKKLpanisedaeeg 504
Cdd:cd08631    81 QYAFQVSDYPVILSLENHCGVEQQQTMAQHLTEILGEKLLSTTLDGVLPTQLPSPEELRGKILLKGKKI----------- 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  505 evsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesge 584
Cdd:cd08631       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  585 dagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmKLSRALSDLVKYTKSVATHDIEME 664
Cdd:cd08631   150 --------------------------------------------------------RLSPELSDCVIYCKSVSFRSFTHS 173

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  665 AASS--WQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRA 742
Cdd:cd08631   174 REHYhfYEISSFTETKARKLIREAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQEMWNAGCQMVALNFQTAGLEMDLNDG 253


                  ....*
gi 732170452  743 KFSAN 747
Cdd:cd08631   254 LFRQN 258
PI-PLCc_delta1 cd08629
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily ...
 345-747 1.72e-88

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: 284.23  E-value: 1.72e-88
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  345 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 424
Cdd:cd08629     1 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVLRAIR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  425 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLdLSSVSSEDATTLPSPQMLKGKILVKGKKLpanisedaeeg 504
Cdd:cd08629    81 DYAFKASPYPVILSLENHCSLEQQRVMARHLRAILGPIL-LDQPLDGVTTSLPSPEQLKGKILLKGKKL----------- 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  505 evsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesge 584
Cdd:cd08629       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  585 dagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmKLSRALSDLVKYTKSVATHDIE-- 662
Cdd:cd08629   149 --------------------------------------------------------KLVPELSDMIIYCKSVHFGGFSsp 172

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  663 -MEAASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNR 741
Cdd:cd08629   173 gTSGQAFYEMASFSESRALRLLQESGNGFVRHNVSCLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYL 252


                  ....*.
gi 732170452  742 AKFSAN 747
Cdd:cd08629   253 GCFQDN 258
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
 348-490 9.45e-85

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: 269.37  E-value: 9.45e-85
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452   348 MTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINKYA 427
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 732170452   428 FIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLdLSSVSSEDATTLPSPQMLKGKILVKG 490
Cdd:pfam00388   81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDML-YTPPLDDDLTELPSPEDLKGKILIKG 142
PI-PLCc_zeta cd08595
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family ...
 345-747 1.67e-84

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: 273.35  E-value: 1.67e-84
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  345 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 424
Cdd:cd08595     1 YQDMDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDGADNEPVVYHGYTLTSKILFKEVITTVE 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  425 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSSVSSEDATTLPSPQMLKGKILVKGKKlpanisedaeeg 504
Cdd:cd08595    81 KYAFEKSDYPVVLSLENHCSTEQQEIMAHYLVSILGEKLLRAPIDDPATGELPSPEALKFKILVKNKK------------ 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  505 evsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesge 584
Cdd:cd08595       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  585 dagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmKLSRALSDLVKYTKSVA----THD 660
Cdd:cd08595   149 --------------------------------------------------------KIAKALSDLVIYTKSEKfcsfTHS 172

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  661 IEMEaaSSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLN 740
Cdd:cd08595   173 RDNQ--HSYENNSIGENKARKLLKSSGADFVGHTQRFITRIYPKGTRASSSNYNPQEFWNVGCQMVALNFQTLGAPMDLQ 250


                  ....*..
gi 732170452  741 RAKFSAN 747
Cdd:cd08595   251 NGKFLDN 257
PI-PLCc_delta3 cd08630
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily ...
 345-747 5.67e-84

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: 271.89  E-value: 5.67e-84
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  345 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 424
Cdd:cd08630     1 FQDMSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVIQAVR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  425 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSSVSSEDATTLPSPQMLKGKILVKGKKLpanisedaeeg 504
Cdd:cd08630    81 QHAFTASPYPVILSLENHCGLEQQAAMARHLQTILGDMLVTQPLDSLNPEELPSPEELKGRVLVKGKKL----------- 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  505 evsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesge 584
Cdd:cd08630       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  585 dagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmKLSRALSDLVKYTKSVATHDIEM- 663
Cdd:cd08630   150 --------------------------------------------------------QISPELSALAVYCQATRLRTLEPa 173

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  664 -EAASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRA 742
Cdd:cd08630   174 pVQPQPCQVSSLSERKAKKLIREAGNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLVALNFQTPGYEMDLNAG 253


                  ....*
gi 732170452  743 KFSAN 747
Cdd:cd08630   254 RFLVN 258
PI-PLCc_gamma2 cd08628
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily ...
 346-747 3.40e-81

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: 264.22  E-value: 3.40e-81
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  346 QDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 425
Cdd:cd08628     2 QDMNNPLSHYWISSSHNTYLTGDQLRSESSTEAYIRCLRMGCRCIELDCWDGPDGKPIIYHGWTRTTKIKFDDVVQAIKD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  426 YAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSSVSSEdATTLPSPQMLKGKILVKGKKLPANisedaeege 505
Cdd:cd08628    82 HAFVTSEYPVILSIEEHCSVEQQRHMAKVFKEVFGDKLLMKPLEAS-ADQLPSPTQLKEKIIIKHKKLIAI--------- 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  506 vsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesged 585
Cdd:cd08628       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  586 agasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmklsrALSDLVKYTKSVATHDIEMEA 665
Cdd:cd08628   152 -----------------------------------------------------------ELSDLVVYCKPTSKTKDNLEN 172

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  666 ASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKFS 745
Cdd:cd08628   173 PDFKEIRSFVETKAPSIIRQKPVQLLKYNRKGLTRVYPKGQRVDSSNYDPFRLWLCGSQMVALNFQTADKYMQLNHALFS 252


                  ..
gi 732170452  746 AN 747
Cdd:cd08628   253 LN 254
PI-PLC1c_yeast cd08598
Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This ...
 346-747 7.17e-81

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: 262.57  E-value: 7.17e-81
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  346 QDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 425
Cdd:cd08598     2 EDLSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDGDDGEPVVTHGYTLTSSVPFRDVCRAIKK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  426 YAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLdLSSVSSEDATTLPSPQMLKGKILVKgkklpanisedaeege 505
Cdd:cd08598    82 YAFVTSPYPLILSLEVHCDAEQQERMVEIMKETFGDLL-VTEPLDGLEDELPSPEELRGKILIK---------------- 144

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  506 vsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedvesged 585
Cdd:cd08598       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  586 agasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmklsralsdlVKYTKSVATHDIemea 665
Cdd:cd08598   145 ----------------------------------------------------------------VKKESKTPNHIF---- 156

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  666 asswqvsSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKFS 745
Cdd:cd08598   157 -------SLSERSLLKLLKDKRAALDKHNRRHLMRVYPSGTRISSSNFNPLPFWRAGVQMVALNWQTYDLGMQLNEAMFA 229


                  ..
gi 732170452  746 AN 747
Cdd:cd08598   230 GS 231
PI-PLCc_beta4 cd08626
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily ...
 345-747 2.18e-76

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: 251.22  E-value: 2.18e-76
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  345 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGP--DGEPIVHHGYTLTSKILFKDVIET 422
Cdd:cd08626     1 YQDMDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGKgeDQEPIITHGKAMCTDILFKDVIQA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  423 INKYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKL---DLSSVSSEDATTLPSPQMLKGKILVKGKKlpanise 499
Cdd:cd08626    81 IKDTAFVTSDYPVILSFENHCSKPQQYKLAKYCEEIFGDLLltkPLESHPLEPGVPLPSPNKLKRKILIKNKR------- 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  500 daeegevsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeed 579
Cdd:cd08626       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  580 vesgedagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmklsraLSDLVKYTKSV--A 657
Cdd:cd08626   154 ------------------------------------------------------------------LSSLVNYAQPVkfQ 167

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  658 THDIEMEAASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRML 737
Cdd:cd08626   168 GFDVAEERNIHFNMSSFNESVGLGYLKTSAIEFVNYNKRQMSRIYPKGTRVDSSNYMPQIFWNAGCQMVSLNFQTPDLGM 247

                         410
                  ....*....|
gi 732170452  738 QLNRAKFSAN 747
Cdd:cd08626   248 QLNQGKFEYN 257
PI-PLCc_epsilon cd08596
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ...
 346-747 1.96e-73

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: 243.22  E-value: 1.96e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  346 QDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 425
Cdd:cd08596     2 EDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGDDGMPIIYHGHTLTTKIPFKDVVEAINR 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  426 YAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLD---LSSVSSEDATTLPSPQMLKGKILVKGKKLPanisedae 502
Cdd:cd08596    82 SAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLVtkfLFESDFSDDPSLPSPLQLKNKILLKNKKAP-------- 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  503 egevsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeedves 582
Cdd:cd08596       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  583 gedagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmklsrALSDLVKYTKSVATHDie 662
Cdd:cd08596   154 --------------------------------------------------------------ELSDLVIYCQAVKFPG-- 169

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  663 MEAASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRA 742
Cdd:cd08596   170 LSTPKCYHISSLNENAAKRLCRRYPQKLVQHTRCQLLRTYPAATRIDSSNPNPLIFWLHGLQLVALNYQTDDLPMHLNAA 249


                  ....*
gi 732170452  743 KFSAN 747
Cdd:cd08596   250 MFEAN 254
PI-PLCc_beta2 cd08624
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily ...
 345-747 2.92e-72

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: 240.34  E-value: 2.92e-72
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  345 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDG--PDGEPIVHHGYTLTSKILFKDVIET 422
Cdd:cd08624     1 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTEILFKDAIEA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  423 INKYAFIKNEYPVILSIENHC-SVIQQKKMAQYLTDILGDKL---DLSSVSSEDATTLPSPQMLKGKILVKGKKLpanis 498
Cdd:cd08624    81 IAESAFKTSPYPVILSFENHVdSPKQQAKMAEYCRTIFGDMLltePLEKYPLKPGVPLPSPEDLRGKILIKNKKY----- 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  499 edaeegevsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaee 578
Cdd:cd08624       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  579 dvesgedagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmklsRALSDLVKYTKSVA- 657
Cdd:cd08624   156 -----------------------------------------------------------------EEMSSLVNYIQPTKf 170

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  658 -THDIEMEAASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRM 736
Cdd:cd08624   171 vSFEFSAQKNRSYVISSFTELKAYDLLSKASVQFVEYNKRQMSRIYPKGTRMDSSNYMPQMFWNVGCQMVALNFQTMDLP 250

                         410
                  ....*....|.
gi 732170452  737 LQLNRAKFSAN 747
Cdd:cd08624   251 MQQNMALFEFN 261
EFh_PI-PLCeta1 cd16220
EF-hand motif found in phosphoinositide phospholipase C eta 1 (PI-PLC-eta1); PI-PLC-eta1, also ...
 193-333 4.67e-72

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: 234.92  E-value: 4.67e-72
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  193 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDHQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 272
Cdd:cd16220     1 WVKQTFEEADKNGDGLLNIEEIYQLMHKLNVNLPRRKVRQMFQEADTDENQGTLTFEEFCVFYKMMSLRRDLYLLLLSYS 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 732170452  273 NHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSPA 333
Cdd:cd16220    81 DKKDHLTVEELAQFLKVEQKMNNVTTEYCLDIIKKFEVSEENKEQNVLGIEGFTNFMRSPA 141
PLN02952 PLN02952
phosphoinositide phospholipase C
 262-887 1.39e-68

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 241.06  E-value: 1.39e-68
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  262 RDLYLLMLTYSNHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEpcpeNK-------SKGLLGIDGFTNYTRSPag 334
Cdd:PLN02952   38 DDVKDVFCKFSVGGGHMGADQLRRFLVLHQDELDCTLAEAQRIVEEVI----NRrhhvtryTRHGLNLDDFFHFLLYD-- 111

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  335 DIFNPEHHHVHQDMTQPLSHYFITSSHNTYLVGDQLMSQ-SRVDMYAwVLQAGCRCVEVDCWDGPDGEPI-VHHGYTLTS 412
Cdd:PLN02952  112 DLNGPITPQVHHDMTAPLSHYFIYTGHNSYLTGNQLSSDcSEVPIVK-ALQRGVRVIELDLWPGSTKDEIlVLHGRTLTT 190

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  413 KILFKDVIETINKYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSsvSSEDATTLPSPQMLKGKILVKGKK 492
Cdd:PLN02952  191 PVPLIKCLKSIRDYAFSSSPYPVIITLEDHLTPDLQAKVAEMATQIFGQMLYYP--ESDSLVQFPSPESLKHRIIISTKP 268

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  493 lPANISEDaeegevsdedsadeidddckllNGDASTNRKrventakrkldslikeskirdcedpnnfsvSTLSPSGKlgR 572
Cdd:PLN02952  269 -PKEYLES----------------------SGPIVIKKK------------------------------NNVSPSGR--N 293

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  573 KSKAEEDVESGEDAGASrrngrlvvgsfsrrkkkgsklkkAASVEEGDEGQDSPGGQSRGATRQKKTM-----KLSRALS 647
Cdd:PLN02952  294 SSEETEEAQTLESMLFE-----------------------QEADSRSDSDQDDNKSGELQKPAYKRLItihagKPKGTLK 350

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  648 DLVKYtksvathdiemeAASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVA 727
Cdd:PLN02952  351 DAMKV------------AVDKVRRLSLSEQELEKAATTNGQDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIA 418

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  728 LNYQSEGRMLQLNRAKFSANGGCGYVLKPGCMCQGVFNPNSEDP---LPgqLKKQLVLRIISGQQLPKPRDSMLGDRGEI 804
Cdd:PLN02952  419 FNMQGYGKSLWLMHGMFRANGGCGYLKKPDFLMKKGFHDEVFDPkkkLP--VKKTLKVKVYLGDGWRLDFSHTHFDSYSP 496

                         570       580       590       600       610       620       630       640
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  805 IDPFVEVEIIGLPVDCSREQTRVVDDNgFNPTWEETLVFMVHMPEIALVRFLVWDHDPIGR-DFIGQRTLAFSSMMPGYR 883
Cdd:PLN02952  497 PDFYTKMYIVGVPADNAKKKTKIIEDN-WYPAWNEEFSFPLTVPELALLRIEVREYDMSEKdDFGGQTCLPVSELRPGIR 575


                  ....
gi 732170452  884 HVYL 887
Cdd:PLN02952  576 SVPL 579
PI-PLCc_gamma1 cd08627
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily ...
 346-747 1.41e-68

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: 228.76  E-value: 1.41e-68
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  346 QDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 425
Cdd:cd08627     2 EEMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  426 YAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLdLSSVSSEDATTLPSPQMLKGKILVKGKKLpanisedaeege 505
Cdd:cd08627    82 HAFVTSEYPIILSIEDHCSIVQQRNMAQHFKKVFGDML-LTKPVDINADGLPSPNQLKRKILIKHKKL------------ 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  506 vsdedsadeidddckllngdastnrkrventakrkldslikeskIRDcedpnnfsvstlspsgklgrkskaeedvesged 585
Cdd:cd08627   149 --------------------------------------------YRD--------------------------------- 151

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  586 agasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmklsralsdlvkytksvathdiemea 665
Cdd:cd08627       --------------------------------------------------------------------------------

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  666 asswqVSSFSETKAHQILQQ-KPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKF 744
Cdd:cd08627   152 -----MSSFPETKAEKYVNRsKGKKFLQYNRRQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALF 226


                  ...
gi 732170452  745 SAN 747
Cdd:cd08627   227 MLG 229
PI-PLCc_beta3 cd08625
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily ...
 347-747 7.69e-67

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: 224.93  E-value: 7.69e-67
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  347 DMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDG--PDGEPIVHHGYTLTSKILFKDVIETIN 424
Cdd:cd08625     3 DMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGrpPEEEPFITHGFTMTTEIPFKDVIEAIA 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  425 KYAFIKNEYPVILSIENHC-SVIQQKKMAQYLTDILGDKL---DLSSVSSEDATTLPSPQMLKGKILVKGKKLPAnised 500
Cdd:cd08625    83 ESAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALlidPLDKYPLVPGVQLPSPQELMGKILVKNKKMST----- 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  501 aeegevsdedsadeidddckLLNGDASTNRKRVENTAKRKldslikeskirdcedpnnfsvstlspsgklgrkskaeedv 580
Cdd:cd08625   158 --------------------LVNYIEPVKFKSFEAAAKRN---------------------------------------- 177

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  581 esgedagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmklsralsdlvKYtksvathd 660
Cdd:cd08625   178 ----------------------------------------------------------------------KF-------- 179

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  661 iemeaassWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLN 740
Cdd:cd08625   180 --------FEMSSFVETKAMEQLTKSPMEFVEYNKKQLSRIYPKGTRVDSSNYMPQLFWNVGCQMVALNFQTLDLAMQLN 251


                  ....*..
gi 732170452  741 RAKFSAN 747
Cdd:cd08625   252 MGVFEYN 258
PLCXc smart00148
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...
 348-491 2.61e-63

Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. These enzymes contain 2 regions (X and Y) which together form a TIM barrel-like structure containing the active site residues. Phospholipase C enzymes (PI-PLC) act as signal transducers that generate two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol. The bacterial enzyme appears to be a homologue of the mammalian PLCs.


Pssm-ID: 197543 [Multi-domain]  Cd Length: 143  Bit Score: 210.60  E-value: 2.61e-63
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452    348 MTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINKYA 427
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 732170452    428 FIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLdLSSVSSEDATTLPSPQMLKGKILVKGK 491
Cdd:smart00148   81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDML-YTPPLTSSLEVLPSPEQLRGKILLKVR 143
PLN02228 PLN02228
Phosphoinositide phospholipase C
 267-887 8.41e-63

Phosphoinositide phospholipase C


Pssm-ID: 177873 [Multi-domain]  Cd Length: 567  Bit Score: 223.76  E-value: 8.41e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  267 LMLTYSnHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNY----TRSPAgdifnPEHH 342
Cdd:PLN02228   29 LFEAYS-RNGKMSFDELLRFVSEVQGERHAGLDYVQDIFHSVKHHNVFHHHGLVHLNAFYRYlfsdTNSPL-----PMSG 102

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  343 HVHQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDG-EPIVHHGYTLTSKILFKDVIE 421
Cdd:PLN02228  103 QVHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSGnAAEVRHGRTLTSHEDLQKCLN 182

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  422 TINKYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKldLSSVSSEDATTLPSPQMLKGKILVKGKKLPANISEDA 501
Cdd:PLN02228  183 AIKDNAFQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGM--LFRCTSESTKHFPSPEELKNKILISTKPPKEYLESKT 260

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  502 EEGEVSD----------EDSADEIDDDCKLLNGDASTNRKRVENTAKRKLDSLikeskiRDC--EDPNnfsvstlspsgK 569
Cdd:PLN02228  261 VQTTRTPtvketswkrvADAENKILEEYKDEESEAVGYRDLIAIHAANCKDPL------KDClsDDPE-----------K 323

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  570 LGRKSKAEEDVEsgedagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkkTMKLSRAlSDL 649
Cdd:PLN02228  324 PIRVSMDEQWLE---------------------------------------------------------TMVRTRG-TDL 345

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  650 VKYTksvathdiemeaasswqvssfsetkahqilqqkpaqylrfnQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALN 729
Cdd:PLN02228  346 VRFT-----------------------------------------QRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFN 384

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  730 YQSEGRMLQLNRAKFSANGGCGYVLKPGCMCQ--GVFNPNSEDPLPGQLKkqlvLRIISGQ--QLPKPRDSMlgDRGEII 805
Cdd:PLN02228  385 MQGHGKQLWIMQGMFRANGGCGYVKKPRILLDehTLFDPCKRLPIKTTLK----VKIYTGEgwDLDFHLTHF--DQYSPP 458

                         570       580       590       600       610       620       630       640
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  806 DPFVEVEIIGLPVDCSREQTRVVDDNGFnPTW-EETLVFMVHMPEIALVRFLVWDHDP-IGRDFIGQRTLAFSSMMPGYR 883
Cdd:PLN02228  459 DFFVKIGIAGVPRDTVSYRTETAVDQWF-PIWgNDEFLFQLRVPELALLWFKVQDYDNdTQNDFAGQTCLPLPELKSGVR 537


                  ....
gi 732170452  884 HVYL 887
Cdd:PLN02228  538 AVRL 541
PI-PLCc_beta1 cd08623
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily ...
 346-747 1.45e-61

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: 210.32  E-value: 1.45e-61
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  346 QDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDG--PDGEPIVHHGYTLTSKILFKDVIETI 423
Cdd:cd08623     2 EDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGrtAEEEPVITHGFTMTTEISFKEVIEAI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  424 NKYAFIKNEYPVILSIENHC-SVIQQKKMAQYLTDILGDKL---DLSSVSSEDATTLPSPQMLKGKILVKGKKlpanise 499
Cdd:cd08623    82 AECAFKTSPFPILLSFENHVdSPKQQAKMAEYCRLIFGDALlmePLEKYPLESGVPLPSPMDLMYKILVKNKK------- 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  500 daeegevsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvstlspsgklgrkskaeed 579
Cdd:cd08623       --------------------------------------------------------------------------------

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  580 vesgedagasrrngrlvvgsfsrrkkkgsklkkaasveegdegqdspggqsrgatrqkktmklsraLSDLVKYTKSVATH 659
Cdd:cd08623   155 ------------------------------------------------------------------MSNLVNYIQPVKFE 168

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  660 DIEMEAA--SSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRML 737
Cdd:cd08623   169 SFEASKKrnKSFEMSSFVETKGLEQLTKSPVEFVEYNKMQLSRIYPKGTRVDSSNYMPQLFWNAGCQMVALNFQTVDLSM 248

                         410
                  ....*....|
gi 732170452  738 QLNRAKFSAN 747
Cdd:cd08623   249 QINMGMYEYN 258
PLN02222 PLN02222
phosphoinositide phospholipase C 2
 283-887 1.42e-60

phosphoinositide phospholipase C 2


Pssm-ID: 177868 [Multi-domain]  Cd Length: 581  Bit Score: 217.59  E-value: 1.42e-60
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  283 LQRFLQVEQKMAGVTLESCQDIIeqfepcpeNKSKGLLG-----IDGFTNYTrspAGDIFNP-EHHHVHQDMTQPLSHYF 356
Cdd:PLN02222   45 LHRFLIDVQKQDKATREDAQSII--------NSASSLLHrnglhLDAFFKYL---FGDNNPPlALHEVHHDMDAPISHYF 113

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  357 ITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPI-VHHGYTLTSKILFKDVIETINKYAFIKNEYPV 435
Cdd:PLN02222  114 IFTGHNSYLTGNQLSSDCSEVPIIDALKKGVRVIELDIWPNSDKDDIdVLHGMTLTTPVGLIKCLKAIRAHAFDVSDYPV 193

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  436 ILSIENHCSVIQQKKMAQYLTDILGDKLdLSSVSSEDATTLPSPQMLKGKILVKGKKlpaniseDAEEGEVSDedsaDEI 515
Cdd:PLN02222  194 VVTLEDHLTPDLQSKVAEMVTEIFGEIL-FTPPVGESLKEFPSPNSLKKRIIISTKP-------PKEYKEGKD----DEV 261

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  516 DDDCKLLnGDastnrkrvENTAKRKLDSLIKESKIRDCEDPNnfsvstlspsgklGRKSKAEEDVESGEDAGASRRNGRL 595
Cdd:PLN02222  262 VQKGKDL-GD--------EEVWGREVPSFIQRNKSVDKNDSN-------------GDDDDDDDDGEDKSKKNAPPQYKHL 319

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  596 VvgsfsrrkkkgsklkkaaSVEEGdegqdSPGGqsrgatrqkktmklsrALSDLVKytksVATHDIEMEAASSWQVSSFS 675
Cdd:PLN02222  320 I------------------AIHAG-----KPKG----------------GITECLK----VDPDKVRRLSLSEEQLEKAA 356

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  676 ETKAHQILqqkpaqylRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKFSANGGCGYVLK 755
Cdd:PLN02222  357 EKYAKQIV--------RFTQHNLLRIYPKGTRVTSSNYNPLVGWSHGAQMVAFNMQGYGRSLWLMQGMFRANGGCGYIKK 428

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  756 PGCMCQG-----VFNPNSEDPLPGQLKkqLVLRIISGQQLPKPRDSMlgDRGEIIDPFVEVEIIGLPVDCSREQTRVVDD 830
Cdd:PLN02222  429 PDLLLKSgsdsdIFDPKATLPVKTTLR--VTIYMGEGWYFDFRHTHF--DQYSPPDFYTRVGIAGVPGDTVMKKTKTLED 504

                         570       580       590       600       610
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 732170452  831 NgFNPTWEETLVFMVHMPEIALVRFLVWDHDPIGR-DFIGQRTLAFSSMMPGYRHVYL 887
Cdd:PLN02222  505 N-WIPAWDEVFEFPLTVPELALLRLEVHEYDMSEKdDFGGQTCLPVWELSQGIRAFPL 561
PI-PLC-Y pfam00387
Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to ...
 646-758 1.76e-57

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


Pssm-ID: 459794  Cd Length: 114  Bit Score: 193.06  E-value: 1.76e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452   646 LSDLVKYTKSVATHDIEM-EAASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQ 724
Cdd:pfam00387    1 LSDLVVYTQSVKFKSFSTpESKTPNHIFSFSESKALKLIKSSSAAFVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNCGVQ 80

                           90       100       110
                   ....*....|....*....|....*....|....
gi 732170452   725 MVALNYQSEGRMLQLNRAKFSANGGCGYVLKPGC 758
Cdd:pfam00387   81 MVALNWQTPDEGMQLNEGMFADNGGCGYVLKPEF 114
PLN02230 PLN02230
phosphoinositide phospholipase C 4
 263-887 1.40e-56

phosphoinositide phospholipase C 4


Pssm-ID: 177875 [Multi-domain]  Cd Length: 598  Bit Score: 206.48  E-value: 1.40e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  263 DLYLLMLTYSNHKDHLDAASLQRFLQVEQKMAGVT-LESCQDIIEQFEPCPENKSKGL---LGIDGFTNYTRSPagDIFN 338
Cdd:PLN02230   30 DVRDLFEKYADGDAHMSPEQLQKLMAEEGGGEGETsLEEAERIVDEVLRRKHHIAKFTrrnLTLDDFNYYLFST--DLNP 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  339 PEHHHVHQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKD 418
Cdd:PLN02230  108 PIADQVHQNMDAPLSHYFIFTGHNSYLTGNQLSSNCSELPIADALRRGVRVVELDLWPRGTDDVCVKHGRTLTKEVKLGK 187

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  419 VIETINKYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSsvSSEDATTLPSPQMLKGKILVKGKK----LP 494
Cdd:PLN02230  188 CLDSIKANAFAISKYPVIITLEDHLTPKLQFKVAKMITQTFGDMLYYH--DSEGCQEFPSPEELKEKILISTKPpkeyLE 265

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  495 ANISED---AEEGEVSDEDSADEIDDDCKLLNGDASTNRKRVENTAKrkldsliKESKIRDCEdpNNFSVSTLSPSGKlg 571
Cdd:PLN02230  266 ANDAKEkdnGEKGKDSDEDVWGKEPEDLISTQSDLDKVTSSVNDLNQ-------DDEERGSCE--SDTSCQLQAPEYK-- 334

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  572 rkskaeedvesgedagasrrngRLVvgsfsrrkkkgsklkkaaSVEEGdegqdSPGGQSRGATRQKKTmKLSRAlsdlvk 651
Cdd:PLN02230  335 ----------------------RLI------------------AIHAG-----KPKGGLRMALKVDPN-KIRRL------ 362

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  652 ytksvathdiemeaasswqvsSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQ 731
Cdd:PLN02230  363 ---------------------SLSEQLLEKAVASYGADVIRFTQKNFLRIYPKGTRFNSSNYKPQIGWMSGAQMIAFNMQ 421

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  732 SEGRMLQLNRAKFSANGGCGYVLKP------GCMCQGVFNPNSEDPlpgqlKKQLVLRIISGQQLPKPRDSMLGDRGEII 805
Cdd:PLN02230  422 GYGRALWLMEGMFRANGGCGYVKKPdflmdaGPNGQDFYPKDNSCP-----KKTLKVKVCMGDGWLLDFKKTHFDSYSPP 496

                         570       580       590       600       610       620       630       640
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  806 DPFVEVEIIGLPVDCSREQTRVVDDNgFNPTWEETLVFMVHMPEIALVRFLVWDHDPIGR-DFIGQRTLAFSSMMPGYRH 884
Cdd:PLN02230  497 DFFVRVGIAGAPVDEVMEKTKIEYDT-WTPIWNKEFIFPLAVPELALLRVEVHEHDINEKdDFGGQTCLPVSEIRQGIHA 575


                  ...
gi 732170452  885 VYL 887
Cdd:PLN02230  576 VPL 578
PI-PLCc_plant cd08599
Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family ...
 345-516 7.21e-55

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: 190.28  E-value: 7.21e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  345 HQDMTQPLSHYFITSSHNTYLVGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 424
Cdd:cd08599     1 HHDMTAPLSHYFIFSSHNSYLTGNQLSSRSSTAPIIEALLRGCRVIELDLWPGGRGDICVLHGGTLTKPVKFEDCIKAIK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  425 KYAFIKNEYPVILSIENHCSVIQQKKMAQYLTDILGDKLDLSSvSSEDATTLPSPQMLKGKILV--KGKKLPANISEDAE 502
Cdd:cd08599    81 ENAFTASEYPVIITLENHLSPELQAKAAQILRETLGDKLFYPD-SEDLPEEFPSPEELKGKILIsdKPPVIRNSLSETQL 159

                         170
                  ....*....|....
gi 732170452  503 EGEVSDEDSADEID 516
Cdd:cd08599   160 KKVIEGEHPTDLIE 173
PH_PLC_eta cd13364
Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of ...
 69-175 1.28e-54

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: 184.79  E-value: 1.28e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452   69 MQEGMQMVKLRGGSKGLVRFYYLDEHRSCIRWRPSRKN-EKAKISIDSIQEVSEGRQSEVFQRYP-DGSFDPNCCFSIYH 146
Cdd:cd13364     1 MQEGSELVKVRSNSRQYRRFFYLDEDKSSIRWKPSKKKsEKAKIPISSIREVREGKTTDIFRSCDiSGDFPEECCFSIIY 80

                          90       100
                  ....*....|....*....|....*....
gi 732170452  147 GSHRESLDLVSTSSEVARTWVTGLRYLMA 175
Cdd:cd13364    81 GEEYETLDLVASSPDEANIWITGLRYLMS 109
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 777-902 1.27e-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: 176.96  E-value: 1.27e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  777 KKQLVLRIISGQQLPKPRDsmlgDRGEIIDPFVEVEIIGLPV-DCSREQTRVVDDNGFNPTWEETLVFMVHMPEIALVRF 855
Cdd:cd00275     1 PLTLTIKIISGQQLPKPKG----DKGSIVDPYVEVEIHGLPAdDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRF 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 732170452  856 LVWDHDPIGRDFIGQRTLAFSSMMPGYRHVYL-----EGMEEASIFVHVAVS 902
Cdd:cd00275    77 VVYDEDSGDDDFLGQACLPLDSLRQGYRHVPLldskgEPLELSTLFVHIDIT 128
PLCYc smart00149
Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ...
 647-759 9.12e-51

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: 174.35  E-value: 9.12e-51
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452    647 SDLVKYTKSVATHDIE--MEAASSWQVSSFSETKAHQILQQKPAQYLRFNQQQLSRIYPSSYRVDSSNYNPQPFWNAGCQ 724
Cdd:smart00149    1 SDLVIYCAPVKFRSFEsaESKNPFYEMSSFSETKAKKLLKKSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGCQ 80

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 732170452    725 MVALNYQSEGRMLQLNRAKFSANGGCGYVLKPGCM 759
Cdd:smart00149   81 MVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115
PI-PLCc cd00137
Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This ...
 345-747 6.72e-47

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: 169.37  E-value: 6.72e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  345 HQDMTQPLSHYFITSSHNTYLVGDQL-----MSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTsKILFKDV 419
Cdd:cd00137     1 HHPDTQPLAHYSIPGTHDTYLTAGQFtikqvWGLTQTEMYRQQLLSGCRCVDIRCWDGKPEEPIIYHGPTFL-DIFLKEV 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  420 IETINKYAFIKNEYPVILSIENHCSVI--QQKKMAQYLTDILGDKldLSSVSSEDATTLPSPQMLKGKILVKGKKlpani 497
Cdd:cd00137    80 IEAIAQFLKKNPPETIIMSLKNEVDSMdsFQAKMAEYCRTIFGDM--LLTPPLKPTVPLPSLEDLRGKILLLNKK----- 152

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  498 sedaeegevsdedsadeidddckllngdastnrkrventakrkldslikeskirdcedpnnfsvSTLSPSGklgrkskae 577
Cdd:cd00137   153 ----------------------------------------------------------------NGFSGPT--------- 159

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  578 edvesgedagasrrngrlvvgsfsrrkkkgsklkkaasveeGDEGQDSPGGQSRGATRQKktmklsralsdlvkytksva 657
Cdd:cd00137   160 -----------------------------------------GSSNDTGFVSFEFSTQKNR-------------------- 178

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  658 thdiemeaasSWQVSSFSETKAHQI----LQQKPAQYLRFNQQQLSRIYPS---------SYRVDSSNYNPQPFWN---A 721
Cdd:cd00137   179 ----------SYNISSQDEYKAYDDekvkLIKATVQFVDYNKNQLSRNYPSgtsggtawyYYAMDSNNYMPQMFWNanpA 248

                         410       420
                  ....*....|....*....|....*.
gi 732170452  722 GCQMVALNYQSEGRMLQLNRAKFSAN 747
Cdd:cd00137   249 GCGIVILDFQTMDLPMQQYMAVIEFN 274
EFh_PRIP cd16206
EF-hand motif found in phospholipase C-related but catalytically inactive proteins (PRIP); ...
 193-332 1.18e-44

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: 157.76  E-value: 1.18e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  193 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFRE--ADTDDHQGTLGFEEFCAFYKMMSTRRDLYLLMLT 270
Cdd:cd16206     1 WLESVFEEADTNKSGFLDEEEAVQLIKQLNPGLSTSRIKQKLKElqKKKDGARGRVSSDEFVELFKELATRPEIYFLLVR 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 732170452  271 YSNHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSP 332
Cdd:cd16206    81 YASNKDYLTVDDLMLFLEAEQGMTGVTKEKCLEIINKYEPSEEGREKGQLGIDGFTRYLLSE 142
EFh_PI-PLCdelta cd16202
EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta ...
 193-332 1.13e-41

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: 149.30  E-value: 1.13e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  193 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDhQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 272
Cdd:cd16202     1 WLKDQFRKADKNGDGKLSFKECKKLLKKLNVKVDKDYAKKLFQEADTSG-EDVLDEEEFVQFYNRLTKRPEIEELFKKYS 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  273 NHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSP 332
Cdd:cd16202    80 GDDEALTVEELRRFLQEEQKVKDVTLEWAEQLIETYEPSEDLKAQGLMSLDGFTLFLLSP 139
PH_PLC_ELMO1 cd01248
Phospholipase C and Engulfment and cell motility protein 1 pleckstrin homology domain; The ...
 69-174 7.26e-40

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: 142.85  E-value: 7.26e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452   69 MQEGMQMVKLRGGSKGLVRFYYLDEHRSCIRWRPSRK-NEKAKISIDSIQEVSEGRQSEVFQRY-PDGSFDPNCCFSIYH 146
Cdd:cd01248     1 LQQGTLLLKYREGSKPKERTFYLDPDGTRITWESSKKkSEKKSIDISDIKEIRPGKDTDGFKRKkKSNKPKEERCFSIIY 80

                          90       100
                  ....*....|....*....|....*...
gi 732170452  147 GSHRESLDLVSTSSEVARTWVTGLRYLM 174
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. ...
 193-333 4.74e-38

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: 138.57  E-value: 4.74e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  193 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTdDHQGTLGFEEFCAFYKMMSTRRDLYLLMLTY- 271
Cdd:cd15898     1 WLRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVDT-NGDGTLTFDEFEELYKSLTERPELEPIFKKYa 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 732170452  272 SNHKDHLDAASLQRFLQVEQKMAgVTLESCQDIIEQFEPCPENKskgLLGIDGFTNYTRSPA 333
Cdd:cd15898    80 GTNRDYMTLEEFIRFLREEQGEN-VSEEECEELIEKYEPERENR---QLSFEGFTNFLLSPE 137
PLN02223 PLN02223
phosphoinositide phospholipase C
 345-887 1.12e-30

phosphoinositide phospholipase C


Pssm-ID: 165867 [Multi-domain]  Cd Length: 537  Bit Score: 128.22  E-value: 1.12e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  345 HQDMTQPLSHYFITSSHNTYLVGDQLMSQS-RVDMYAWVLQAGCRCVEVDCWdgPDGEP--IVHHGYTLTSKILFKDVIE 421
Cdd:PLN02223  105 HHDMHAPLSHYFIHTSLKSYFTGNNVFGKLySIEPIIDALEQGVRVVELDLL--PDGKDgiCVRPKWNFEKPLELQECLD 182

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  422 TINKYAFIK-NEYPVILSIENHCSVIQQKKMAQYLTDILGDKldlssVSSEDAT----TLPSPQMLKGKILVKgKKLPAn 496
Cdd:PLN02223  183 AIKEHAFTKcRSYPLIITFKDGLKPDLQSKATQMIDQTFGDM-----VYHEDPQhsleEFPSPAELQNKILIS-RRPPK- 255

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  497 isedaeegevsdedsadeidddcKLLNGDASTNRKRVENtakrkldslikESKIRD-CEDPNNFSV---STLSPSGKLgr 572
Cdd:PLN02223  256 -----------------------ELLYAKADDGGVGVRN-----------ELEIQEgPADKNYQSLvgfHAVEPRGML-- 299

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  573 kskaeEDVESGEDAGASRrngrlvvgsfsrrkkkgsklkkaasveegdegqdsPGGQSRgatrqkktmklsralsDLVKY 652
Cdd:PLN02223  300 -----QKALTGKADDIQQ-----------------------------------PGWYER----------------DIISF 323

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  653 TKSvathdiemeaasswqvssfsetkahQILQQKPaqylrfnQQQLSRIYPSsyrvdssnYNPQPFWNAGCQMVALNYQS 732
Cdd:PLN02223  324 TQK-------------------------KFLRTRP-------KKKNLLINAP--------YKPQRAWMHGAQLIALSRKD 363

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  733 EGRMLQLNRAKFSANGGCGYVLKPGCMCQ----GVFNPnSEDPLpgqLKKQLVLRIISGQ-----------QLPKPrdsm 797
Cdd:PLN02223  364 DKEKLWLMQGMFRANGGCGYVKKPDFLLNagpsGVFYP-TENPV---VVKILKVKIYMGDgwivdfkkrigRLSKP---- 435

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  798 lgdrgeiiDPFVEVEIIGLPVDCSREQTrVVDDNGFNPTWEETLVFMVHMPEIALVRFLVWDHDPIGRD-FIGQRTLAFS 876
Cdd:PLN02223  436 --------DLYVRISIAGVPHDEKIMKT-TVKNNEWKPTWGEEFTFPLTYPDLALISFEVYDYEVSTADaFCGQTCLPVS 506

                         570
                  ....*....|.
gi 732170452  877 SMMPGYRHVYL 887
Cdd:PLN02223  507 ELIEGIRAVPL 517
EFh_PRIP1 cd16222
EF-hand motif found in phospholipase C-related but catalytically inactive protein 1 (PRIP-1); ...
 193-332 5.33e-28

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: 110.34  E-value: 5.33e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  193 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDHQGT--LGFEEFCAFYKMMSTRRDLYLLMLT 270
Cdd:cd16222     1 WLSAVFEAADVDGYGIMLEDTAVELIKQLNPGIKEAKIRLKFKEIQKSKEKLTtrVTEEEFCEAYSELCTRPEVYFLLVQ 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 732170452  271 YSNHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSP 332
Cdd:cd16222    81 ISKNKEYLDAKDLMLFLEAEQGMTHITEEMCLDIIRRYEPSQEGRLKGFLGIDGFTQYLLSS 142
EFh_PRIP2 cd16223
EF-hand motif found in phospholipase C-related but catalytically inactive protein 2 (PRIP-2); ...
 193-332 4.86e-26

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: 104.60  E-value: 4.86e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  193 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFRE-ADTDDHQGT-LGFEEFCAFYKMMSTRRDLYLLMLT 270
Cdd:cd16223     1 WLSQMFVEADTDNVGHITLCRAVQFIKNLNPGLKTSKIELKFKElHKSKEKGGTeVTKEEFIEVFHELCTRPEIYFLLVQ 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 732170452  271 YSNHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSP 332
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, ...
 193-332 2.93e-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: 102.23  E-value: 2.93e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  193 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDhQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 272
Cdd:cd16219     1 WIRDWFQKADKNKDGRMNFKEVRDLLKMMNVDMNEEHALRLFQMADKSE-SGTLEGEEFVLFYKALTQREDVLKIFQDFS 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  273 NHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSP 332
Cdd:cd16219    80 ADGQKLTLLEFVDFLQQEQLERENTEELAMELIDRYEPSDTAKKLHALSIDGFLMYLCSP 139
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 779-887 7.85e-22

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: 91.01  E-value: 7.85e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452    779 QLVLRIISGQQLPKPrdsmlgDRGEIIDPFVEVEIIGLPVdcSREQTRVVDDNGfNPTWEETLVFMVHMPEIALVRFLVW 858
Cdd:smart00239    1 TLTVKIISARNLPPK------DKGGKSDPYVKVSLDGDPK--EKKKTKVVKNTL-NPVWNETFEFEVPPPELAELEIEVY 71

                            90       100       110
                    ....*....|....*....|....*....|
gi 732170452    859 DHDPIGRD-FIGQRTLAFSSMMPGYRHVYL 887
Cdd:smart00239   72 DKDRFGRDdFIGQVTIPLSDLLLGGRHEKL 101
PI-PLCc_GDPD_SF cd08555
Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases ...
 359-464 2.31e-21

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: 92.50  E-value: 2.31e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  359 SSHNTYLVGDQlmsQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLT------SKILFKDVIETINKYAFiKNE 432
Cdd:cd08555     2 LSHRGYSQNGQ---ENTLEAFYRALDAGARGLELDVRLTKDGELVVYHGPTLDrttagiLPPTLEEVLELIADYLK-NPD 77

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 732170452  433 YPVILSIENHCSV----IQQKKMAQYLTDILGDKLD 464
Cdd:cd08555    78 YTIILSLEIKQDSpeydEFLAKVLKELRVYFDYDLR 113
PH_PLC_delta cd13363
Phospholipase C-delta (PLC-delta) pleckstrin homology (PH) domain; The PLC-delta (PLCdelta) ...
 69-187 7.18e-21

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: 88.91  E-value: 7.18e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452   69 MQEGMQMVKLRGGSKGLVRFYYLDEHRSCIrWRPSRK---NEKAKISIDSIQEVSEGRQSEVFQRYPDgSFDPNCCFSI- 144
Cdd:cd13363     1 LLQGSPLLKVRSRSWKKERFYKLQEDCKTV-WHESKKtrsNSKQTFSIEDIESVREGHQSEGLRKYAE-AFPEDRCFSIv 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 732170452  145 YHGsHRESLDLVSTSSEVARTWVTGLRYLMAGIsdeDSLARRQ 187
Cdd:cd13363    79 FKG-RRKNLDLIAPSEEEAQRWVRGLEKLIARL---TNMSQRE 117
C2 pfam00168
C2 domain;
779-884 5.18e-20

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 85.83  E-value: 5.18e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452   779 QLVLRIISGQQLPKPrdsmlgDRGEIIDPFVEVEIIGlpvDCSREQTRVVDdNGFNPTWEETLVFMVHMPEIALVRFLVW 858
Cdd:pfam00168    2 RLTVTVIEAKNLPPK------DGNGTSDPYVKVYLLD---GKQKKKTKVVK-NTLNPVWNETFTFSVPDPENAVLEIEVY 71

                           90       100
                   ....*....|....*....|....*..
gi 732170452   859 DHDPIGRD-FIGQRTLAFSSMMPGYRH 884
Cdd:pfam00168   72 DYDRFGRDdFIGEVRIPLSELDSGEGL 98
EFh_ScPlc1p_like cd16207
EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar ...
 190-333 1.34e-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: 1.34e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  190 RDQWlKQTfDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTdDHQGTLGFEEFCAFYKMMSTRRDLYLLML 269
Cdd:cd16207     2 RIHW-KRA-DSKKQDGDERLDFEDVEKLCRRLHINCSESYLRELFDKADT-DKKGYLNFEEFQEFVKLLKRRKDIKAIFK 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 732170452  270 TY-SNHKDHLDAASLQRFLQVEQKmAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSPA 333
Cdd:cd16207    79 QLtKPGSDGLTLEEFLKFLRDVQK-EDVDRETWEKIFEKFARRIDDSDSLTMTLEGFTSFLLSSY 142
EFh_PI-PLCdelta1 cd16217
EF-hand motif found in phosphoinositide phospholipase C delta 1 (PI-PLC-delta1); PI-PLC-delta1, ...
 193-332 4.31e-16

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: 75.93  E-value: 4.31e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  193 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDhQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 272
Cdd:cd16217     1 WIHSCLRKADKNKDNKMSFKELKDFLKEINIEVDDDYAEKLFKECDKSK-SGFLEGEEIEEFYKLLTKREEIDVIFGEYA 79

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  273 NHKDHLDAASLQRFLQVEQKMAgVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSP 332
Cdd:cd16217    80 KSDGTMSRNNLLNFLQEEQREE-VAPAYALSLIEKYEPDETAKAQRQMTKDGFLMYLLSP 138
PH_PLC_plant-like cd13365
Plant-like Phospholipase C (PLC) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) was the ...
 61-175 2.01e-15

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: 73.47  E-value: 2.01e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452   61 RVERCMGAMQEGMQMVKL--RGGSKglVRFYYLDEHRSCIRWRPSRKNEKAKISIDSIQEVSEGRQSEVFQRYPDGSFDp 138
Cdd:cd13365     2 DVIEAITQLKIGSYLLKYgrRGKPH--FRYFWLSPDELTLYWSSPKKGSEKRVRLSSVSRIIPGQRTVVFKRPPPPGLE- 78

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 732170452  139 NCCFSIYHGSHRESLDLVSTSSEVARTWVTGLRYLMA 175
Cdd:cd13365    79 EHSFSIIYADGERSLDLTCKDRQEFDTWFTGLRYLLS 115
PH_PLC_gamma cd13362
Phospholipase C-gamma (PLC-gamma) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is ...
 93-175 4.94e-15

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: 72.31  E-value: 4.94e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452   93 EHRSCIRWRPSRKNEKAKISIDSIQEVSEGRQSEVFQRYPDGS--FDPNCCFSIYHGSH--RESLDLVSTSSEVARTWVT 168
Cdd:cd13362    26 ETRQVVWSRGGGKRAEGAVDIREIKEIRPGKNSKDFERWPDEAkkLDPSCCFVILYGTEfrLKTLSVAATSEEECDMWIK 105


                  ....*..
gi 732170452  169 GLRYLMA 175
Cdd:cd13362   106 GLRYLVE 112
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 780-870 7.27e-15

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: 71.33  E-value: 7.27e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  780 LVLRIISGQQLPKPrdsmlgDRGEIIDPFVEVEIIGLpvdcSREQTRVVDDNgFNPTWEETLVFMVHMPEIALVRFLVWD 859
Cdd:cd00030     1 LRVTVIEARNLPAK------DLNGKSDPYVKVSLGGK----QKFKTKVVKNT-LNPVWNETFEFPVLDPESDTLTVEVWD 69

                          90
                  ....*....|..
gi 732170452  860 HDPIGRD-FIGQ 870
Cdd:cd00030    70 KDRFSKDdFLGE 81
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 193-259 8.97e-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: 66.80  E-value: 8.97e-14
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 732170452  193 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDHqGTLGFEEFCafyKMMS 259
Cdd:cd00051     1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGD-GKIDFEEFL---ELMA 63
EF-hand_like pfam09279
Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...
 254-338 2.22e-13

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: 66.50  E-value: 2.22e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452   254 FYKMMSTRRDLYLLMLTYSNHKDHLDAASLQRFLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSPA 333
Cdd:pfam09279    1 FYKMLTQREEIDEIFQEYSGDGQKLSLDELVDFLREEQREEDASPALALSLIERYEPSETAKKQHAMTKDGFLMYLCSPD 80


                   ....*
gi 732170452   334 GDIFN 338
Cdd:pfam09279   81 GSIFN 85
EF-hand_7 pfam13499
EF-hand domain pair;
191-256 4.30e-13

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 64.97  E-value: 4.30e-13
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 732170452   191 DQWLKQTFDEADKNGDGSLSIGEVLQLLHKL--NVNLPRQRVKQMFREADTdDHQGTLGFEEFCAFYK 256
Cdd:pfam13499    1 EEKLKEAFKLLDSDGDGYLDVEELKKLLRKLeeGEPLSDEEVEELFKEFDL-DKDGRISFEEFLELYS 67
EFh_PI-PLCdelta3 cd16218
EF-hand motif found in phosphoinositide phospholipase C delta 3 (PI-PLC-delta3); PI-PLC-delta3, ...
 193-333 1.35e-12

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: 65.92  E-value: 1.35e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  193 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADT------DDHQgtlgFEEFCAfyKMMStRRDLYL 266
Cdd:cd16218     1 WIHEYLRRADLNKDGKMSFEEIKDLLQMINIDLNEQYAYQLFKECDRsnddrlEEHE----IEEFCR--RLMQ-RPELEE 73

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 732170452  267 LMLTYSNHKDHLDAASLQRFLQvEQKMAGvTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSPA 333
Cdd:cd16218    74 IFHQYSGEDCVLSAEELREFLK-DQGEDA-SLVHAKELIQTYELNEKAKQHQLMTLDGFTMYMLSKD 138
EFh_PI-PLCzeta cd16204
EF-hand motif found in phosphoinositide phospholipase C zeta 1 (PI-PLC-zeta1); PI-PLC-zeta1, ...
 206-331 7.56e-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: 64.06  E-value: 7.56e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  206 DGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDhQGTLGFEEFCAFYKMMSTRRDLYLLMLTYSNHKDHLDAASLQR 285
Cdd:cd16204    16 KGKINLESTLKLLEKLDIPFDYIHVKYIFKKNDSFK-AGNITIEDFRAIYRAIAHRCEIHEIFNTYSENRKILSAPNLVG 94

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 732170452  286 FLQVEQKMAGVTLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRS 331
Cdd:cd16204    95 FLKKEQFQDEADETIASELIAKYEPIEEVRKRKQMSFEGFIRYMTS 140
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
183-254 2.20e-10

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 59.42  E-value: 2.20e-10
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 732170452  183 LARRQRTRDQWLKQTFDEADKNGDGSLSIGEVLQLLHKLNVnlPRQRVKQMFREADTdDHQGTLGFEEFCAF 254
Cdd:COG5126    60 ESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTALGV--SEEEADELFARLDT-DGDGKISFEEFVAA 128
PH_12 pfam16457
Pleckstrin homology domain;
63-174 9.64e-10

Pleckstrin homology domain;


Pssm-ID: 465123 [Multi-domain]  Cd Length: 128  Bit Score: 57.65  E-value: 9.64e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452    63 ERCMGAMQEGMQMVKLRGGSKGL-VRFYYLDEHRSCIRW---------RPSRKNEKAKISIDSIQEVSEGRQSEVF--QR 130
Cdd:pfam16457    3 EQRLNCLLEGAWFPKVRGRRRKKkYRFCRLSPNRKVLHYgdfeekptvDPSLESLPEKIDLSDIKEVVTGKECPHVreSG 82

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 732170452   131 YPDGSFDPNCCFSIYHGSH-RESLDLVSTSSEVARTWVTGLRYLM 174
Cdd:pfam16457   83 KKSKKTSSTLAFSLIYGADeYELLDFVAPSESVAAIWLDGLNMLL 127
PI-PLCc_bacteria_like cd08557
Catalytic domain of bacterial phosphatidylinositol-specific phospholipase C and similar ...
 351-488 1.43e-08

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: 57.10  E-value: 1.43e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  351 PLSHYFITSSHNTYlvgDQLMSQSRVDMYAWV----------LQAGCRCVEVDCW-DGPDGEPIVHHGYTLTSKILFKDV 419
Cdd:cd08557     8 PLSQLSIPGTHNSY---AYTIDGNSPIVSKWSktqdlsitdqLDAGVRYLDLRVAyDPDDGDLYVCHGLFLLNGQTLEDV 84

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 732170452  420 IETINkyAFIK---NEyPVILSIENHCSVI---QQKKMAQYLTDILGDKLDLSSVSSEDATTLpSpQMLKGKILV 488
Cdd:cd08557    85 LNEVK--DFLDahpSE-VVILDLEHEYGGDngeDHDELDALLRDVLGDPLYRPPVRAGGWPTL-G-ELRAGKRVL 154
EFh_PI-PLCbeta cd16200
EF-hand motif found in metazoan phosphoinositide-specific phospholipase C (PI-PLC)-beta ...
 213-332 5.56e-08

EF-hand motif found in metazoan phosphoinositide-specific phospholipase C (PI-PLC)-beta isozymes; PI-PLC-beta isozymes represent a class of metazoan PI-PLCs that hydrolyze the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) to propagate diverse intracellular responses that underlie the physiological action of many hormones, neurotransmitters, and growth factors (EC 3.1.4.11). They have been implicated in numerous processes relevant to central nervous system (CNS), including chemotaxis, cardiovascular function, neuronal signaling, and opioid sensitivity. Like other PI-PLC isozymes, PI-PLC-beta isozymes contain a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. Besides, they have a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are four PI-PLC-beta isozymes (1-4). PI-PLC-beta1 and PI-PLC-beta3 are expressed in a wide range of tissues and cell types, whereas PI-PLC-beta2 and PI-PLC-beta4 have been found only in hematopoietic and neuronal tissues, respectively. All PI-PLC-beta isozymes are activated by the heterotrimeric G protein alpha subunits of the Gq class through their C2 domain and long C-terminal extension. They are GTPase-activating proteins (GAPs) for these G alpha(q) proteins. PI-PLC-beta2 and PI-PLC-beta3 can also be activated by beta-gamma subunits of the G alpha(i/o) family of heterotrimeric G proteins and the small GTPases such as Rac and Cdc42. This family also includes two invertebrate homologs of PI-PLC-beta, PLC21 from cephalopod retina and No receptor potential A protein (NorpA) from Drosophila melanogaster.


Pssm-ID: 320030 [Multi-domain]  Cd Length: 153  Bit Score: 53.02  E-value: 5.56e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  213 EVLQLLHKLNvnLPRQRVKQMFREADTDDHqgtlgfeeFCAFYKMMSTRRDLYLLMLTYS-NHKDHLDAASLQRFLQVEQ 291
Cdd:cd16200    34 RVLKALKALG--LPDGKNDEIDPEDFTFEK--------FFKLYNKLCPRPDIDEIFKELGgKRKPYLTLEQLVDFLNEEQ 103

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 732170452  292 ---KMAGV-----TLESCQDIIEQFEPCPENKSKGLLGIDGFTNYTRSP 332
Cdd:cd16200   104 rdpRLNEIlfpfhTKEQAKKLIDKYEPNEKNKKKGQLTLEGFLRYLMSD 152
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 777-870 9.33e-08

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: 51.86  E-value: 9.33e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  777 KKQLVLRIISGQQLPKPRDSMLGDrgeiidPFVEVEIIGLPVDCSREQTRVVDdNGFNPTWEETLVFMVHMPEIALVRFL 856
Cdd:cd04031    15 TSQLIVTVLQARDLPPRDDGSLRN------PYVKVYLLPDRSEKSKRRTKTVK-KTLNPEWNQTFEYSNVRRETLKERTL 87

                          90
                  ....*....|....*...
gi 732170452  857 ---VWDHDPIG-RDFIGQ 870
Cdd:cd04031    88 evtVWDYDRDGeNDFLGE 105
EH cd00052
Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and ...
 195-252 1.02e-06

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: 46.83  E-value: 1.02e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 732170452  195 KQTFDEADKNGDGSLSIGEVLQLLhkLNVNLPRQRVKQMFREADTdDHQGTLGFEEFC 252
Cdd:cd00052     2 DQIFRSLDPDGDGLISGDEARPFL--GKSGLPRSVLAQIWDLADT-DKDGKLDKEEFA 56
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
190-263 1.48e-06

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 48.63  E-value: 1.48e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 732170452  190 RDQWLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTdDHQGTLGFEEFCAFYKMMSTRRD 263
Cdd:COG5126    31 FRRLWATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDT-DGDGKISADEFRRLLTALGVSEE 103
EFh_PI-PLCgamma cd16201
EF-hand motif found in phosphoinositide phospholipase C gamma isozymes (PI-PLC-gamma); ...
 193-292 2.20e-06

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: 48.34  E-value: 2.20e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  193 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDdHQGTLGFEEFCAFY-------KMMSTRRDLY 265
Cdd:cd16201     1 WLRKEFYSMDRTRRETVTLKDLKAFLPRVNCKISTNKLREKFQEVDTR-RRGELGFDDFAQLYhklmfdqKIIEDFFKKY 79

                          90       100
                  ....*....|....*....|....*..
gi 732170452  266 llmlTYSNHKDHLDAASLQRFLQVEQK 292
Cdd:cd16201    80 ----SYSSDGQTVTLEDFQRFLLEEQK 102
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 764-884 3.29e-06

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: 47.58  E-value: 3.29e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  764 FNPNSEdplpgqlkkQLVLRIISGQQLPKPrdsmlgDRGEIIDPFVEVEIIGLPVDCSREQTRVVDDNgFNPTWEETLVF 843
Cdd:cd00276     9 YLPTAE---------RLTVVVLKARNLPPS------DGKGLSDPYVKVSLLQGGKKLKKKKTSVKKGT-LNPVFNEAFSF 72

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 732170452  844 MV---HMPEIALVrFLVWDHDPIGRD-FIGQRTLAFSSMMPGYRH 884
Cdd:cd00276    73 DVpaeQLEEVSLV-ITVVDKDSVGRNeVIGQVVLGPDSGGEELEH 116
PTZ00184 PTZ00184
calmodulin; Provisional
 183-261 4.16e-06

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 47.45  E-value: 4.16e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  183 LARRQRTRD--QWLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDhQGTLGFEEFCafyKMMST 260
Cdd:PTZ00184   73 MARKMKDTDseEEIKEAFKVFDRDGNGFISAAELRHVMTNLGEKLTDEEVDEMIREADVDG-DGQINYEEFV---KMMMS 148


                  .
gi 732170452  261 R 261
Cdd:PTZ00184  149 K 149
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 806-875 5.12e-06

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: 46.87  E-value: 5.12e-06
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 732170452  806 DPFVEVEIIGLPVDCSREQTRVVDDNgFNPTWEETLVFMVHMPEiaLVRFL---VWDHDPIGR-DFIGqrTLAF 875
Cdd:cd04026    35 DPYVKLKLIPDPKNETKQKTKTIKKT-LNPVWNETFTFDLKPAD--KDRRLsieVWDWDRTTRnDFMG--SLSF 103
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 779-866 6.01e-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: 46.03  E-value: 6.01e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  779 QLVLRIISGQQLPkprdsmlgdrGEIIDPFVEVEIIGlpvdcSREQTRVVDDNGfNPTWEETLVFMVHMP--EI--ALVR 854
Cdd:cd04011     5 QVRVRVIEARQLV----------GGNIDPVVKVEVGG-----QKKYTSVKKGTN-CPFYNEYFFFNFHESpdELfdKIIK 68

                          90
                  ....*....|..
gi 732170452  855 FLVWDHDPIGRD 866
Cdd:cd04011    69 ISVYDSRSLRSD 80
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 779-890 6.71e-06

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: 46.46  E-value: 6.71e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  779 QLVLRIISGQQLpKPRDSmlgdRGeIIDPFVEVEIigLP----VDCSREQTRVVDDNgFNPTWEETLVFMV----HMPEI 850
Cdd:cd04009    17 SLRVEILNARNL-LPLDS----NG-SSDPFVKVEL--LPrhlfPDVPTPKTQVKKKT-LFPLFDESFEFNVppeqCSVEG 87

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 732170452  851 ALVRFLVWDHDPIGR-DFIGQRTLAFSSmMPGYRHVYLEGM 890
Cdd:cd04009    88 ALLLFTVKDYDLLGSnDFEGEAFLPLND-IPGVEDTSSAQG 127
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
 194-262 1.35e-05

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: 46.44  E-value: 1.35e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 732170452  194 LKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTdDHQGTLGFEEF---CAFykMMSTRR 262
Cdd:cd16185    68 MQNGFEQRDTSRSGRLDANEVHEALAASGFQLDPPAFQALFRKFDP-DRGGSLGFDDYielCIF--LASARN 136
EFh_PI-PLC21 cd16213
EF-hand motif found in phosphoinositide phospholipase PLC21 and similar proteins; The family ...
 246-328 1.89e-05

EF-hand motif found in phosphoinositide phospholipase PLC21 and similar proteins; The family includes invertebrate homologs of phosphoinositide phospholipase C beta (PI-PLC-beta) named PLC21 from cephalopod retina. It also includes PLC21 encoded by plc-21 gene, which is expressed in the central nervous system of Drosophila. Like beta-class of vertebrate PI-PLCs, PLC21 contains 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.


Pssm-ID: 320043  Cd Length: 154  Bit Score: 45.76  E-value: 1.89e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  246 LGFEEFCAFYKMMSTRRDLYLLMLTYSN-HKDHLDAASLQRFLQVEQKMAGV--------TLESCQDIIEQFEPCPENKS 316
Cdd:cd16213    58 FTFEDFFNFYRRLTGRQEVEKIFDELGAkKKPYLTTEQFVDFLNKTQRDPRLneilypyaNPKRARDLINQYEPNKSFAK 137

                          90
                  ....*....|..
gi 732170452  317 KGLLGIDGFTNY 328
Cdd:cd16213   138 KGHLSVEGFLRY 149
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
 194-260 7.81e-05

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: 44.13  E-value: 7.81e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 732170452  194 LKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTdDHQGTLGFEEFCAFYKMMST 260
Cdd:cd16185     2 LRQWFRAVDRDRSGSIDVNELQKALAGGGLLFSLATAEKLIRMFDR-DGNGTIDFEEFAALHQFLSN 67
EFh_PI-PLCbeta4 cd16211
EF-hand motif found in phosphoinositide phospholipase C beta 4 (PI-PLC-beta4); PI-PLC-beta4, ...
 248-331 8.56e-05

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: 43.95  E-value: 8.56e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  248 FEEFCAFYKMMSTRRDLYLLMLTYS-NHKDHLDAASLQRFLQVEQKMAGVT--------LESCQDIIEQFEPCPENKSKG 318
Cdd:cd16211    59 FEKFYELYHKICPRTDIEELFKKINgDKKDYLTVDQLISFLNEHQRDPRLNeilfpfydRKRVMQIIETYEVDEEFKKKE 138

                          90
                  ....*....|...
gi 732170452  319 LLGIDGFTNYTRS 331
Cdd:cd16211   139 QLSSDGFCRYLMS 151
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
194-308 1.38e-04

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 42.86  E-value: 1.38e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  194 LKQTFDEADKNGDGSLSIGEVLQLLHklnvnlprQRVKQMFREADTdDHQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS- 272
Cdd:COG5126     7 LDRRFDLLDADGDGVLERDDFEALFR--------RLWATLFSEADT-DGDGRISREEFVAGMESLFEATVEPFARAAFDl 77

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 732170452  273 ---NHKDHLDAASLQRFLQVeqkmAGVTLESCQDIIEQF 308
Cdd:COG5126    78 ldtDGDGKISADEFRRLLTA----LGVSEEEADELFARL 112
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 780-884 1.47e-04

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: 42.70  E-value: 1.47e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  780 LVLRIISGQQLPKPrdsmlgDRGEIIDPFVEVEIigLPVDCSREQTRVVDDNgFNPTWEETLVFMVHMPEIALVRFL--- 856
Cdd:cd08386    18 LTLKILKAVELPAK------DFSGTSDPFVKIYL--LPDKKHKLETKVKRKN-LNPHWNETFLFEGFPYEKLQQRVLylq 88

                          90       100       110
                  ....*....|....*....|....*....|....
gi 732170452  857 VWDH------DPIGRDFIGQRTLAFSSMMPGYRH 884
Cdd:cd08386    89 VLDYdrfsrnDPIGEVSLPLNKVDLTEEQTFWKD 122
EF-hand_10 pfam14788
EF hand;
209-258 1.82e-04

EF hand;


Pssm-ID: 405477  Cd Length: 50  Bit Score: 40.09  E-value: 1.82e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 732170452   209 LSIGEVLQLLHKLNVNLPRQRVKQMFREADTdDHQGTLGFEEFCAFYKMM 258
Cdd:pfam14788    2 MSFKELKNFLRLINIEVDDSYARKLFQKCDT-SQSGRLEGEEIEEFYKLL 50
EFh_PI-PLCgamma1_like cd16216
EF-hand motif found in 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like ...
 193-294 2.03e-04

EF-hand motif found in 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like proteins; This family corresponds to a small group of uncharacterized 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like (PI-PLC-gamma1-like) proteins. Although their biological function remains unclear, they shows high sequence similarity with other phosphoinositide phospholipase C gamma proteins. They 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. 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.


Pssm-ID: 320046  Cd Length: 150  Bit Score: 42.61  E-value: 2.03e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  193 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRV---KQMFREADTDdhqgtLGFEEFCAFYK--MMSTRRDLyLL 267
Cdd:cd16216     1 WLRKQFDGMDRSREGSITVKDLKALLPQVNYRVPNMRFlrdKLVEVEARSE-----LTFPHFIQFYKnlMFDAQKSI-IE 74

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 732170452  268 MLTYSNHKDHLDAASL--------QRFLQVEQKMA 294
Cdd:cd16216    75 QLELSFPLRNVDRPELcqislydfQKFLQHDQKES 109
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
 194-256 2.96e-04

Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds to Group I PEF proteins that have been found not only in higher animals but also in lower animals, plants, fungi and protists. Group I PEF proteins include apoptosis-linked gene 2 protein (ALG-2), peflin and similar proteins. ALG-2, also termed programmed cell death protein 6 (PDCD6), is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination. Peflin is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+.


Pssm-ID: 320055 [Multi-domain]  Cd Length: 164  Bit Score: 42.52  E-value: 2.96e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 732170452  194 LKQTFDEADKNGDGSLSIGEvLQLLHKLNVNLPRQR--VKQMFREADTDDHqGTLGFEEFCAFYK 256
Cdd:cd16180     2 LRRIFQAVDRDRSGRISAKE-LQRALSNGDWTPFSIetVRLMINMFDRDRS-GTINFDEFVGLWK 64
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 780-899 4.19e-04

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. 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-II topology.


Pssm-ID: 175989 [Multi-domain]  Cd Length: 127  Bit Score: 41.17  E-value: 4.19e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  780 LVLRIISGQQLPkPRDSMLGdrgeiIDPFVEVEIiglpvDCSREQTRVVDDNgFNPTWEETLVFMVHMPEIALVRFL--- 856
Cdd:cd04022     2 LVVEVVDAQDLM-PKDGQGS-----SSAYVELDF-----DGQKKRTRTKPKD-LNPVWNEKLVFNVSDPSRLSNLVLevy 69

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 732170452  857 VWDH--DPIGRDFIGQRTLAFSSMMPGYRHVYLE-GMEEASIFVHV 899
Cdd:cd04022    70 VYNDrrSGRRRSFLGRVRISGTSFVPPSEAVVQRyPLEKRGLFSRV 115
C2_SRC2_like cd04051
C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production ...
 780-909 4.29e-04

C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production is a response to pathogen infiltration. The initial response of increased Ca2+ concentrations are coupled to downstream signal transduction pathways via calcium binding proteins. SRC2 contains a single C2 domain which localizes to the plasma membrane and is involved in Ca2+ dependent protein binding. 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: 176016 [Multi-domain]  Cd Length: 125  Bit Score: 41.06  E-value: 4.29e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  780 LVLRIISGQQL--PKPRDSMlgdrgeiiDPFVEVEIIGLpvdcSREQTRVVDDNGFNPTWEETLVFMVHMPEI----ALV 853
Cdd:cd04051     2 LEITIISAEDLknVNLFGKM--------KVYAVVWIDPS----HKQSTPVDRDGGTNPTWNETLRFPLDERLLqqgrLAL 69

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 732170452  854 RFLVWDHDPIGRD-FIGQRTLAFSSMMPGYrhvyleGMEEASIFVHVAVSDISGKVK 909
Cdd:cd04051    70 TIEVYCERPSLGDkLIGEVRVPLKDLLDGA------SPAGELRFLSYQLRRPSGKPQ 120
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 775-869 6.57e-04

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: 6.57e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  775 QLKKQLVLRIISGQQLpKPRDSmlgdrGEIIDPFVEVEIIGLPVDCSREQTRVVDdNGFNPTWEETLVFMVHMPEIA--- 851
Cdd:cd04035    12 PANSALHCTIIRAKGL-KAMDA-----NGLSDPYVKLNLLPGASKATKLRTKTVH-KTRNPEFNETLTYYGITEEDIqrk 84

                          90
                  ....*....|....*...
gi 732170452  852 LVRFLVWDHDPIGRDFIG 869
Cdd:cd04035    85 TLRLLVLDEDRFGNDFLG 102
C2A_Synaptotagmin-15-17 cd08390
C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...
 775-865 1.00e-03

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. 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: 176036 [Multi-domain]  Cd Length: 123  Bit Score: 39.93  E-value: 1.00e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  775 QLKKQLVLRIISGQQLPkPRDSMLGDRgeiiDPFVEVEIigLPVDCSREQTRVVDDnGFNPTWEETLVFMVHMPEI--AL 852
Cdd:cd08390    11 LEEEQLTVSLIKARNLP-PRTKDVAHC----DPFVKVCL--LPDERRSLQSKVKRK-TQNPNFDETFVFQVSFKELqrRT 82

                          90
                  ....*....|....*....
gi 732170452  853 VRFLVWD------HDPIGR 865
Cdd:cd08390    83 LRLSVYDvdrfsrHCIIGH 101
C2A_fungal cd04041
C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C ...
 799-862 1.21e-03

C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C (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: 176006 [Multi-domain]  Cd Length: 111  Bit Score: 39.55  E-value: 1.21e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  799 GDRGEI-IDPFVEVEI--IGLPVDCsreqTRVVDDNgFNPTWEETLVFMVHMPEIAL---VRFLVWDHDP 862
Cdd:cd04041    16 ADFGTGsSDPYVTASFakFGKPLYS----TRIIRKD-LNPVWEETWFVLVTPDEVKAgerLSCRLWDSDR 80
C2_plant_PLD cd04015
C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds ...
 782-869 1.22e-03

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: 40.75  E-value: 1.22e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  782 LRIISGQQLPKPRDSMLGDRGEII--DPFVEVEIIGLPVdcsrEQTRVVDDNGfNPTWEET-LVFMVHMpeIALVRFLVW 858
Cdd:cd04015    33 FSKLVGCSEPTLKRPSSHRHVGKItsDPYATVDLAGARV----ARTRVIENSE-NPVWNESfHIYCAHY--ASHVEFTVK 105

                          90
                  ....*....|.
gi 732170452  859 DHDPIGRDFIG 869
Cdd:cd04015   106 DNDVVGAQLIG 116
PTZ00184 PTZ00184
calmodulin; Provisional
 195-261 1.61e-03

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 40.13  E-value: 1.61e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 732170452  195 KQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDHqGTLGFEEFCAfykMMSTR 261
Cdd:PTZ00184   14 KEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGN-GTIDFPEFLT---LMARK 76
C2_putative_Elicitor-responsive_gene cd04049
C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive ...
 805-873 1.92e-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: 39.24  E-value: 1.92e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 732170452  805 IDPFVEVEiiglpvdCsREQTR---VVDDNGFNPTWEETLVFMVHMPEIALVRFL---VWDHDPI-GRDFIGQRTL 873
Cdd:cd04049    22 IDPYVIIQ-------C-RTQERkskVAKGDGRNPEWNEKFKFTVEYPGWGGDTKLilrIMDKDNFsDDDFIGEATI 89
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
 805-869 2.08e-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: 40.00  E-value: 2.08e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 732170452  805 IDPFVEVEIigLPVDC--SREQTRVVDDNGfNPTWEETLVFMVHMPE---IALVRFLVWDHDPIGR-DFIG 869
Cdd:cd04020    48 SDSFVKCYL--LPDKSkkSKQKTPVVKKSV-NPVWNHTFVYDGVSPEdlsQACLELTVWDHDKLSSnDFLG 115
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
 191-260 2.92e-03

Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds to Group I PEF proteins that have been found not only in higher animals but also in lower animals, plants, fungi and protists. Group I PEF proteins include apoptosis-linked gene 2 protein (ALG-2), peflin and similar proteins. ALG-2, also termed programmed cell death protein 6 (PDCD6), is a widely expressed calcium-binding modulator protein associated with cell proliferation and death, as well as cell survival. It forms a homodimer in the cell or a heterodimer with its closest paralog peflin. Among the PEF proteins, ALG-2 can bind three Ca2+ ions through its EF1, EF3, and EF5 hands, where it is unique in that its EF5 hand binds Ca2+ ion in a canonical coordination. Peflin is a ubiquitously expressed 30-kD PEF protein containing five EF-hand motifs in its C-terminal domain and a longer N-terminal hydrophobic domain (NHB domain) than any other member of the PEF family. The NHB domain harbors nine repeats of a nonapeptide (A/PPGGPYGGP). Peflin may modulate the function of ALG-2 in Ca2+ signaling. It exists only as a heterodimer with ALG-2, and binds two Ca2+ ions through its EF1 and EF3 hands. Its additional EF5 hand is unpaired and does not bind Ca2+ ion but mediates the heterodimerization with ALG-2. The dissociation of heterodimer occurs in the presence of Ca2+.


Pssm-ID: 320055 [Multi-domain]  Cd Length: 164  Bit Score: 39.43  E-value: 2.92e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 732170452  191 DQWlKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQRVKQMFREADTDDhQGTLGFEEF---CAFYKMMST 260
Cdd:cd16180    67 QDW-RRLFRRFDRDRSGSIDFNELQNALSSFGYRLSPQFVQLLVRKFDRRR-RGSISFDDFveaCVTLKRLTD 137
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 230-258 3.32e-03

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: 35.82  E-value: 3.32e-03
                            10        20
                    ....*....|....*....|....*....
gi 732170452    230 VKQMFREADTdDHQGTLGFEEFCAFYKMM 258
Cdd:smart00054    2 LKEAFRLFDK-DGDGKIDFEEFKDLLKAL 29
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
 194-221 3.54e-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: 35.84  E-value: 3.54e-03
                           10        20
                   ....*....|....*....|....*...
gi 732170452   194 LKQTFDEADKNGDGSLSIGEVLQLLHKL 221
Cdd:pfam00036    2 LKEIFRLFDKDGDGKIDFEEFKELLKKL 29
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
 229-258 4.90e-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: 35.45  E-value: 4.90e-03
                           10        20        30
                   ....*....|....*....|....*....|
gi 732170452   229 RVKQMFREADTdDHQGTLGFEEFCAFYKMM 258
Cdd:pfam00036    1 ELKEIFRLFDK-DGDGKIDFEEFKELLKKL 29
EF-hand_6 pfam13405
EF-hand domain;
193-222 5.06e-03

EF-hand domain;


Pssm-ID: 463869 [Multi-domain]  Cd Length: 30  Bit Score: 35.62  E-value: 5.06e-03
                           10        20        30
                   ....*....|....*....|....*....|
gi 732170452   193 WLKQTFDEADKNGDGSLSIGEVLQLLHKLN 222
Cdd:pfam13405    1 ELREAFKLFDKDGDGKISLEELRKALRSLG 30
C2A_Copine cd04048
C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
 784-870 5.48e-03

C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a protein involved in membrane trafficking, protein-protein interactions, and perhaps even cell division and growth. 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: 176013 [Multi-domain]  Cd Length: 120  Bit Score: 37.93  E-value: 5.48e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  784 IISGQQLPKPrdsmlgDRGEIIDPFVEVEIIGLPVDCSRE--QTRVVDDNgFNPTWEETLVFMVHMPEIALVRFLVWDHD 861
Cdd:cd04048     6 SISCRNLLDK------DVLSKSDPFVVVYVKTGGSGQWVEigRTEVIKNN-LNPDFVTTFTVDYYFEEVQKLRFEVYDVD 78

                          90
                  ....*....|....
gi 732170452  862 PIGR-----DFIGQ 870
Cdd:cd04048    79 SKSKdlsdhDFLGE 92
C2_Calpain cd04046
C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, ...
 800-874 7.87e-03

C2 domain present in Calpain proteins; A single C2 domain is found in calpains (EC 3.4.22.52, EC 3.4.22.53), calcium-dependent, non-lysosomal cysteine proteases. Caplains are classified as belonging to Clan CA by MEROPS and include six families: C1, C2, C10, C12, C28, and C47. 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: 176011 [Multi-domain]  Cd Length: 126  Bit Score: 37.64  E-value: 7.87e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 732170452  800 DRGEIIDPFVeveIIglpvDCSRE--QTRVVDDNgFNPTWEETLVFMVHMPEIALVrFLVWDHDPIGRDFIGQRTLA 874
Cdd:cd04046    19 DSGGGADPYV---II----KCEGEsvRSPVQKDT-LSPEFDTQAIFYRKKPRSPIK-IQVWNSNLLCDEFLGQATLS 86
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 780-880 8.55e-03

C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. 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 fifth C2 repeat, C2E, and has a type-II topology.


Pssm-ID: 176005 [Multi-domain]  Cd Length: 115  Bit Score: 37.16  E-value: 8.55e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 732170452  780 LVLRIISGQQLPKprdsmlGDRGEIIDPFVEVEIIGLPVdcsrEQTRVVDDNgFNPTWEETLVFMVHMPEIALVRFLVWD 859
Cdd:cd04040     1 LTVDVISAENLPS------ADRNGKSDPFVKFYLNGEKV----FKTKTIKKT-LNPVWNESFEVPVPSRVRAVLKVEVYD 69

                          90       100
                  ....*....|....*....|..
gi 732170452  860 HDPIGR-DFIGQRTLAFSSMMP 880
Cdd:cd04040    70 WDRGGKdDLLGSAYIDLSDLEP 91
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
 794-870 9.40e-03

C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both proteins contain two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding 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. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175991 [Multi-domain]  Cd Length: 123  Bit Score: 37.46  E-value: 9.40e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 732170452  794 RDSMLGDRGEIIDPFVEVEIIGLpvdcSREqTRVVDDNGFnPTWEETLVFMVHMPEIALVRFLVWDHDPIGR-DFIGQ 870
Cdd:cd04025    10 RDLAPKDRNGTSDPFVRVFYNGQ----TLE-TSVVKKSCY-PRWNEVFEFELMEGADSPLSVEVWDWDLVSKnDFLGK 81
C2A_Tricalbin-like cd04044
C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 784-845 9.64e-03

C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. 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-II topology.


Pssm-ID: 176009 [Multi-domain]  Cd Length: 124  Bit Score: 37.15  E-value: 9.64e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 732170452  784 IISGQQLpKPRDSMLGDrgeiIDPFVEVEIIGLPVDcsrEQTRVVDDNgFNPTWEETLVFMV 845
Cdd:cd04044     8 IKSARGL-KGSDIIGGT----VDPYVTFSISNRREL---ARTKVKKDT-SNPVWNETKYILV 60
 
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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