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Conserved domains on  [gi|1799905226|ref|XP_031987832|]
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1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase eta-2 isoform X2 [Corvus moneduloides]

Protein Classification

PLC family C2 domain-containing protein( domain architecture ID 11598630)

PLC (phosphoinositide-specific phospholipase C) family C2 domain-containing protein similar to C2 domain region of PLCs that are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG)

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PI-PLCc_GDPD_SF super family cl14615
Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases ...
 321-734 9.07e-159

Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases superfamily; The PI-PLC-like phosphodiesterases superfamily represents the catalytic domains of bacterial phosphatidylinositol-specific phospholipase C (PI-PLC, EC 4.6.1.13), eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11), glycerophosphodiester phosphodiesterases (GP-GDE, EC 3.1.4.46), sphingomyelinases D (SMases D) (sphingomyelin phosphodiesterase D, EC 3.1.4.41) from spider venom, SMases D-like proteins, and phospholipase D (PLD) from several pathogenic bacteria, as well as their uncharacterized homologs found in organisms ranging from bacteria and archaea to metazoans, plants, and fungi. PI-PLCs are ubiquitous enzymes hydrolyzing the membrane lipid phosphoinositides to yield two important second messengers, inositol phosphates and diacylglycerol (DAG). GP-GDEs play essential roles in glycerol metabolism and catalyze the hydrolysis of glycerophosphodiesters to sn-glycerol-3-phosphate (G3P) and the corresponding alcohols that are major sources of carbon and phosphate. Both, PI-PLCs and GP-GDEs, can hydrolyze the 3'-5' phosphodiester bonds in different substrates, and utilize a similar mechanism of general base and acid catalysis with conserved histidine residues, which consists of two steps, a phosphotransfer and a phosphodiesterase reaction. This superfamily also includes Neurospora crassa ankyrin repeat protein NUC-2 and its Saccharomyces cerevisiae counterpart, Phosphate system positive regulatory protein PHO81, glycerophosphodiester phosphodiesterase (GP-GDE)-like protein SHV3 and SHV3-like proteins (SVLs). The residues essential for enzyme activities and metal binding are not conserved in these sequence homologs, which might suggest that the function of catalytic domains in these proteins might be distinct from those in typical PLC-like phosphodiesterases.


The actual alignment was detected with superfamily member cd08633:

Pssm-ID: 472694 [Multi-domain]  Cd Length: 254  Bit Score: 485.31  E-value: 9.07e-159
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  321 NQDMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 400
Cdd:cd08633      1 NQDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  401 KYAFIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKLDLSSVHSDDSTKLPSPASLKGKILVKGKklpanisddaeeg 480
Cdd:cd08633     81 KYAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLDLSSVISNDCTRLPSPEILKGKILVKGK------------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  481 evsdedsadeidddcklmngdasanrkrveniakkkldslikeskirdcedpnnftvstlpspgkaglksdskkskledd 560
Cdd:cd08633        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  561 vetgedfsaskrhsrslmgsfskrkkkgsklkkassleegeddsdsqgnlarssvhysrvnrqkktmKLSRALSDLVKYT 640
Cdd:cd08633    148 -------------------------------------------------------------------KLSRALSDLVKYT 160

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  641 KSVGIHDVETELSSSWQVSSFSETKAHQILQQKPAQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVALNYQSE 720
Cdd:cd08633    161 KSVRVHDIETEATSSWQVSSFSETKAHQILQQKPAQYLRFNQRQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSE 240

                          410
                   ....*....|....
gi 1799905226  721 GRMLQLNRAKFSAN 734
Cdd:cd08633    241 GRMLQLNRAKFSAN 254
EFh_PI-PLCeta2 cd16221
EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also ...
 169-309 6.80e-98

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: 311.10  E-value: 6.80e-98
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  169 WLKQTFDEADKNGDGSLSISEVLQLMHKLNVNLPRQKVKQMFKEADTDANQGTLDFEEFCAFYKMMSTRRDLYLLMLTYS 248
Cdd:cd16221      1 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEADTDDNQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1799905226  249 NHKDYLDTDDLKRFLETEQKMTNVTKEHCLEIISKFEPCPENKKEGALGIDGFTNYMRSPS 309
Cdd:cd16221     81 NHKDHLDTNDLQRFLEVEQKMAGVTREHCLEIISQFEPCSENKQNGALGIDGFTNYMRSPA 141
PH_PLC_eta cd13364
Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of ...
 45-151 1.29e-53

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: 182.87  E-value: 1.29e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226   45 MQMGTQMIKLRGGSKGLVRFYYLDDHRSCIRWRPSRKN-EKAKISIDSIQEVCEGKQSEIFQRY-ADGSFDPNCCFSIYY 122
Cdd:cd13364      1 MQEGSELVKVRSNSRQYRRFFYLDEDKSSIRWKPSKKKsEKAKIPISSIREVREGKTTDIFRSCdISGDFPEECCFSIIY 80

                           90       100
                   ....*....|....*....|....*....
gi 1799905226  123 GDHMESLDLVSSSAEEARTWITGLKYLMA 151
Cdd:cd13364     81 GEEYETLDLVASSPDEANIWITGLRYLMS 109
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 764-888 3.88e-53

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: 182.36  E-value: 3.88e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  764 KKQLVLRIISGQQLPKPRDsmlgDRGEIIDPFVEVEVIGLPV-DCFKEQTRVVDDNGFNPMWEETLVFTVHMPEIALIRF 842
Cdd:cd00275      1 PLTLTIKIISGQQLPKPKG----DKGSIVDPYVEVEIHGLPAdDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRF 76

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1799905226  843 LVWDHDPIGRDFIGQRTIAFSSMMPGYRHVYL-----EGIEEASIFVHVAI 888
Cdd:cd00275     77 VVYDEDSGDDDFLGQACLPLDSLRQGYRHVPLldskgEPLELSTLFVHIDI 127
PRK07764 super family cl35613
DNA polymerase III subunits gamma and tau; Validated
 957-1111 1.73e-04

DNA polymerase III subunits gamma and tau; Validated


The actual alignment was detected with superfamily member PRK07764:

Pssm-ID: 236090 [Multi-domain]  Cd Length: 824  Bit Score: 46.52  E-value: 1.73e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  957 DTKDSSSAGAGEEQEVEAASQPRFVQEPESASPAPAPRDGAGGEAPGKGlkGKAQGSPKGPRQSCAHP---GAPFSEPLP 1033
Cdd:PRK07764   626 APAPAGAAAAPAEASAAPAPGVAAPEHHPKHVAVPDASDGGDGWPAKAG--GAAPAAPPPAPAPAAPAapaGAAPAQPAP 703

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1799905226 1034 RAHKVRLQEPQGEKQSVFARCAINSSGRIGVATNCMKCMIGSKESPDPEGPWSDHPGRPIARDPLHPEQGSSAEERVE 1111
Cdd:PRK07764   704 APAATPPAGQADDPAAQPPQAAQGASAPSPAADDPVPLPPEPDDPPDPAGAPAQPPPPPAPAPAAAPAAAPPPSPPSE 781
 
Name Accession Description Interval E-value
PI-PLCc_eta2 cd08633
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...
 321-734 9.07e-159

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: 485.31  E-value: 9.07e-159
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  321 NQDMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 400
Cdd:cd08633      1 NQDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  401 KYAFIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKLDLSSVHSDDSTKLPSPASLKGKILVKGKklpanisddaeeg 480
Cdd:cd08633     81 KYAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLDLSSVISNDCTRLPSPEILKGKILVKGK------------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  481 evsdedsadeidddcklmngdasanrkrveniakkkldslikeskirdcedpnnftvstlpspgkaglksdskkskledd 560
Cdd:cd08633        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  561 vetgedfsaskrhsrslmgsfskrkkkgsklkkassleegeddsdsqgnlarssvhysrvnrqkktmKLSRALSDLVKYT 640
Cdd:cd08633    148 -------------------------------------------------------------------KLSRALSDLVKYT 160

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  641 KSVGIHDVETELSSSWQVSSFSETKAHQILQQKPAQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVALNYQSE 720
Cdd:cd08633    161 KSVRVHDIETEATSSWQVSSFSETKAHQILQQKPAQYLRFNQRQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSE 240

                          410
                   ....*....|....
gi 1799905226  721 GRMLQLNRAKFSAN 734
Cdd:cd08633    241 GRMLQLNRAKFSAN 254
EFh_PI-PLCeta2 cd16221
EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also ...
 169-309 6.80e-98

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: 311.10  E-value: 6.80e-98
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  169 WLKQTFDEADKNGDGSLSISEVLQLMHKLNVNLPRQKVKQMFKEADTDANQGTLDFEEFCAFYKMMSTRRDLYLLMLTYS 248
Cdd:cd16221      1 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEADTDDNQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1799905226  249 NHKDYLDTDDLKRFLETEQKMTNVTKEHCLEIISKFEPCPENKKEGALGIDGFTNYMRSPS 309
Cdd:cd16221     81 NHKDHLDTNDLQRFLEVEQKMAGVTREHCLEIISQFEPCSENKQNGALGIDGFTNYMRSPA 141
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
 324-466 3.06e-83

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: 268.99  E-value: 3.06e-83
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  324 MSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINKYA 403
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1799905226  404 FIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKLDLSSVHsDDSTKLPSPASLKGKILVKG 466
Cdd:pfam00388   81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLD-DDLTELPSPEDLKGKILIKG 142
PLCXc smart00148
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...
 324-467 1.94e-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: 212.53  E-value: 1.94e-63
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226   324 MSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINKYA 403
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1799905226   404 FIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKLDLSSVHSdDSTKLPSPASLKGKILVKGK 467
Cdd:smart00148   81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTS-SLEVLPSPEQLRGKILLKVR 143
PLN02952 PLN02952
phosphoinositide phospholipase C
 211-874 2.52e-61

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 222.18  E-value: 2.52e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  211 KEADTDANQGTLDFEEFCAF---YKMMSTR--RDLYLLMLTYSNHKDYLDTDDLKRFLETEQKMTNVT----KEHCLEII 281
Cdd:PLN02952     6 KTESYNNDSGSYNYKMFNLFnrkFKITEAEppDDVKDVFCKFSVGGGHMGADQLRRFLVLHQDELDCTlaeaQRIVEEVI 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  282 SKFEPCPENKKEGaLGIDGFTNYMRSPsgDIFNPEHYQVNQDMSYPLSHYFITSSHNTYLMGDQLMSQ-SRVDMYAwVLQ 360
Cdd:PLN02952    86 NRRHHVTRYTRHG-LNLDDFFHFLLYD--DLNGPITPQVHHDMTAPLSHYFIYTGHNSYLTGNQLSSDcSEVPIVK-ALQ 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  361 SGCRCVEVDCWDGPDGEPI-VHHGYTLTSKILFKDVIETINKYAFIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKL 439
Cdd:PLN02952   162 RGVRVIELDLWPGSTKDEIlVLHGRTLTTPVPLIKCLKSIRDYAFSSSPYPVIITLEDHLTPDLQAKVAEMATQIFGQML 241

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  440 DLSsvHSDDSTKLPSPASLKGKILVKGKklPANisddaeegevsdedsadeidddcKLMNGDASANRKRVENIAKKKlds 519
Cdd:PLN02952   242 YYP--ESDSLVQFPSPESLKHRIIISTK--PPK-----------------------EYLESSGPIVIKKKNNVSPSG--- 291

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  520 liKESKIRDCEdpnnftVSTLPSPgKAGLKSDSKKSKLEDDVETGEDfsASKRHSRSLmgsfskrkkkgsklkkasslee 599
Cdd:PLN02952   292 --RNSSEETEE------AQTLESM-LFEQEADSRSDSDQDDNKSGEL--QKPAYKRLI---------------------- 338

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  600 geddsdsqgnlarsSVHysrVNRQKKTMKlsRALSDLVKYTKSVGIHDVETElssswqvsSFSETKAHQIlqqkpaqyLR 679
Cdd:PLN02952   339 --------------TIH---AGKPKGTLK--DAMKVAVDKVRRLSLSEQELE--------KAATTNGQDV--------VR 383

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  680 FNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVALNYQSEGRMLQLNRAKFSANGNCGYVLKPNCMCQGVFNPNSEDP- 758
Cdd:PLN02952   384 FTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFRANGGCGYLKKPDFLMKKGFHDEVFDPk 463

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  759 --LPgqLKKQLVLRIISGQQLPKPRDSMLGDRGEIIDPFVEVEVIGLPVDCFKEQTRVVDDNgFNPMWEETLVFTVHMPE 836
Cdd:PLN02952   464 kkLP--VKKTLKVKVYLGDGWRLDFSHTHFDSYSPPDFYTKMYIVGVPADNAKKKTKIIEDN-WYPAWNEEFSFPLTVPE 540

                          650       660       670
                   ....*....|....*....|....*....|....*....
gi 1799905226  837 IALIRFLVWDHDPIGR-DFIGQRTIAFSSMMPGYRHVYL 874
Cdd:PLN02952   541 LALLRIEVREYDMSEKdDFGGQTCLPVSELRPGIRSVPL 579
PH_PLC_eta cd13364
Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of ...
 45-151 1.29e-53

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: 182.87  E-value: 1.29e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226   45 MQMGTQMIKLRGGSKGLVRFYYLDDHRSCIRWRPSRKN-EKAKISIDSIQEVCEGKQSEIFQRY-ADGSFDPNCCFSIYY 122
Cdd:cd13364      1 MQEGSELVKVRSNSRQYRRFFYLDEDKSSIRWKPSKKKsEKAKIPISSIREVREGKTTDIFRSCdISGDFPEECCFSIIY 80

                           90       100
                   ....*....|....*....|....*....
gi 1799905226  123 GDHMESLDLVSSSAEEARTWITGLKYLMA 151
Cdd:cd13364     81 GEEYETLDLVASSPDEANIWITGLRYLMS 109
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 764-888 3.88e-53

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: 182.36  E-value: 3.88e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  764 KKQLVLRIISGQQLPKPRDsmlgDRGEIIDPFVEVEVIGLPV-DCFKEQTRVVDDNGFNPMWEETLVFTVHMPEIALIRF 842
Cdd:cd00275      1 PLTLTIKIISGQQLPKPKG----DKGSIVDPYVEVEIHGLPAdDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRF 76

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1799905226  843 LVWDHDPIGRDFIGQRTIAFSSMMPGYRHVYL-----EGIEEASIFVHVAI 888
Cdd:cd00275     77 VVYDEDSGDDDFLGQACLPLDSLRQGYRHVPLldskgEPLELSTLFVHIDI 127
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 766-874 2.01e-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: 93.71  E-value: 2.01e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226   766 QLVLRIISGQQLPKPrdsmlgDRGEIIDPFVEVEVIGLPVDCFKeqTRVVDDNGfNPMWEETLVFTVHMPEIALIRFLVW 845
Cdd:smart00239    1 TLTVKIISARNLPPK------DKGGKSDPYVKVSLDGDPKEKKK--TKVVKNTL-NPVWNETFEFEVPPPELAELEIEVY 71

                            90       100       110
                    ....*....|....*....|....*....|
gi 1799905226   846 DHDPIGRD-FIGQRTIAFSSMMPGYRHVYL 874
Cdd:smart00239   72 DKDRFGRDdFIGQVTIPLSDLLLGGRHEKL 101
C2 pfam00168
C2 domain;
766-871 3.01e-20

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 87.37  E-value: 3.01e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  766 QLVLRIISGQQLPKPrdsmlgDRGEIIDPFVEVEVIGlpvDCFKEQTRVVDdNGFNPMWEETLVFTVHMPEIALIRFLVW 845
Cdd:pfam00168    2 RLTVTVIEAKNLPPK------DGNGTSDPYVKVYLLD---GKQKKKTKVVK-NTLNPVWNETFTFSVPDPENAVLEIEVY 71

                           90       100
                   ....*....|....*....|....*..
gi 1799905226  846 DHDPIGRD-FIGQRTIAFSSMMPGYRH 871
Cdd:pfam00168   72 DYDRFGRDdFIGEVRIPLSELDSGEGL 98
EF-hand_like pfam09279
Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...
 230-314 3.67e-17

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: 78.06  E-value: 3.67e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  230 FYKMMSTRRDLYLLMLTYSNHKDYLDTDDLKRFLETEQKMTNVTKEHCLEIISKFEPCPENKKEGALGIDGFTNYMRSPS 309
Cdd:pfam09279    1 FYKMLTQREEIDEIFQEYSGDGQKLSLDELVDFLREEQREEDASPALALSLIERYEPSETAKKQHAMTKDGFLMYLCSPD 80


                   ....*
gi 1799905226  310 GDIFN 314
Cdd:pfam09279   81 GSIFN 85
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
159-230 6.56e-11

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 61.73  E-value: 6.56e-11
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1799905226  159 LSKRQRTRDQWLKQTFDEADKNGDGSLSISEVLQLMHKLNVnlPRQKVKQMFKEADTDANqGTLDFEEFCAF 230
Cdd:COG5126     60 ESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTALGV--SEEEADELFARLDTDGD-GKISFEEFVAA 128
PH_12 pfam16457
Pleckstrin homology domain;
37-150 3.34e-10

Pleckstrin homology domain;


Pssm-ID: 465123 [Multi-domain]  Cd Length: 128  Bit Score: 59.58  E-value: 3.34e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226   37 VVERCMSSMQMGTQMIKLRGGSKGL-VRFYYLDDHRSCIRW---------RPSRKNEKAKISIDSIQEVCEGKQSEIFQR 106
Cdd:pfam16457    1 VKEQRLNCLLEGAWFPKVRGRRRKKkYRFCRLSPNRKVLHYgdfeekptvDPSLESLPEKIDLSDIKEVVTGKECPHVRE 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1799905226  107 YADGSF--DPNCCFSIYYGDHM-ESLDLVSSSAEEARTWITGLKYLM 150
Cdd:pfam16457   81 SGKKSKktSSTLAFSLIYGADEyELLDFVAPSESVAAIWLDGLNMLL 127
PTZ00184 PTZ00184
calmodulin; Provisional
 171-237 2.63e-07

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 51.69  E-value: 2.63e-07
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1799905226  171 KQTFDEADKNGDGSLSISEVLQLMHKLNVNLPRQKVKQMFKEADTDANqGTLDFEEFCAfykMMSTR 237
Cdd:PTZ00184    14 KEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGN-GTIDFPEFLT---LMARK 76
PRK07764 PRK07764
DNA polymerase III subunits gamma and tau; Validated
 957-1111 1.73e-04

DNA polymerase III subunits gamma and tau; Validated


Pssm-ID: 236090 [Multi-domain]  Cd Length: 824  Bit Score: 46.52  E-value: 1.73e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  957 DTKDSSSAGAGEEQEVEAASQPRFVQEPESASPAPAPRDGAGGEAPGKGlkGKAQGSPKGPRQSCAHP---GAPFSEPLP 1033
Cdd:PRK07764   626 APAPAGAAAAPAEASAAPAPGVAAPEHHPKHVAVPDASDGGDGWPAKAG--GAAPAAPPPAPAPAAPAapaGAAPAQPAP 703

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1799905226 1034 RAHKVRLQEPQGEKQSVFARCAINSSGRIGVATNCMKCMIGSKESPDPEGPWSDHPGRPIARDPLHPEQGSSAEERVE 1111
Cdd:PRK07764   704 APAATPPAGQADDPAAQPPQAAQGASAPSPAADDPVPLPPEPDDPPDPAGAPAQPPPPPAPAPAAAPAAAPPPSPPSE 781
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 205-234 1.85e-04

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


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 40.05  E-value: 1.85e-04
                            10        20        30
                    ....*....|....*....|....*....|
gi 1799905226   205 KVKQMFKEADTDANqGTLDFEEFCAFYKMM 234
Cdd:smart00054    1 ELKEAFRLFDKDGD-GKIDFEEFKDLLKAL 29
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 47-151 5.89e-03

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 38.30  E-value: 5.89e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226    47 MGTQMIKLRGGSKGLVRFY-YLDDHRSCI---RWRPSRKNEKAKISIDSIQeVCEGKQSEifqryadgSFDPNCCFSIYY 122
Cdd:smart00233    4 EGWLYKKSGGGKKSWKKRYfVLFNSTLLYyksKKDKKSYKPKGSIDLSGCT-VREAPDPD--------SSKKPHCFEIKT 74

                            90       100
                    ....*....|....*....|....*....
gi 1799905226   123 GDHmESLDLVSSSAEEARTWITGLKYLMA 151
Cdd:smart00233   75 SDR-KTLLLQAESEEEREKWVEALRKAIA 102
 
Name Accession Description Interval E-value
PI-PLCc_eta2 cd08633
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...
 321-734 9.07e-159

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: 485.31  E-value: 9.07e-159
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  321 NQDMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 400
Cdd:cd08633      1 NQDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  401 KYAFIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKLDLSSVHSDDSTKLPSPASLKGKILVKGKklpanisddaeeg 480
Cdd:cd08633     81 KYAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLDLSSVISNDCTRLPSPEILKGKILVKGK------------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  481 evsdedsadeidddcklmngdasanrkrveniakkkldslikeskirdcedpnnftvstlpspgkaglksdskkskledd 560
Cdd:cd08633        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  561 vetgedfsaskrhsrslmgsfskrkkkgsklkkassleegeddsdsqgnlarssvhysrvnrqkktmKLSRALSDLVKYT 640
Cdd:cd08633    148 -------------------------------------------------------------------KLSRALSDLVKYT 160

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  641 KSVGIHDVETELSSSWQVSSFSETKAHQILQQKPAQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVALNYQSE 720
Cdd:cd08633    161 KSVRVHDIETEATSSWQVSSFSETKAHQILQQKPAQYLRFNQRQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSE 240

                          410
                   ....*....|....
gi 1799905226  721 GRMLQLNRAKFSAN 734
Cdd:cd08633    241 GRMLQLNRAKFSAN 254
PI-PLCc_eta cd08594
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family ...
 321-734 1.24e-133

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: 415.35  E-value: 1.24e-133
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  321 NQDMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 400
Cdd:cd08594      1 NQDMTQPLSHYFIASSHNTYLTGDQLLSQSRVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKILFRDVIETIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  401 KYAFIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKLDLSSVHSDDSTKLPSPASLKGKILVKGKKlpanisddaeeg 480
Cdd:cd08594     81 KYAFIKNEYPVILSIENHCSVQQQKKMAQYLKEILGDKLDLSSVISGDSKQLPSPQSLKGKILIKGKK------------ 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  481 evsdedsadeidddcklmngdasanrkrveniakkkldslikeskirdcedpnnFTVSTLPspgkaglksdskkskledd 560
Cdd:cd08594    149 ------------------------------------------------------WQVSSFS------------------- 155

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  561 vetgedfsaskrhsrslmgsfskrkkkgsklkkassleegeddsdsqgnlarssvhysrvnrqkktmklsralsdlvkyt 640
Cdd:cd08594        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  641 ksvgihdvetelssswqvssfsETKAHQILQQKPAQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVALNYQSE 720
Cdd:cd08594    156 ----------------------ETRAHQIVQQKAAQFLRFNQRQLSRIYPSAYRIDSSNFNPQPYWNAGCQLVALNYQTE 213

                          410
                   ....*....|....
gi 1799905226  721 GRMLQLNRAKFSAN 734
Cdd:cd08594    214 GRMLQLNRAKFRAN 227
PI-PLCc_eta1 cd08632
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily ...
 321-734 1.01e-121

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: 383.23  E-value: 1.01e-121
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  321 NQDMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 400
Cdd:cd08632      1 NQDMDQPLCNYFIASSHNTYLTGDQLLSQSKVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKITFRDVIETIN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  401 KYAFIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKLDLSSVHSDDSTKLPSPASLKGKILVKGKklpanisddaeeg 480
Cdd:cd08632     81 KYAFVKNEFPVILSIENHCSIQQQKKIAQYLKEIFGDKLDLSSVLTGDPKQLPSPQLLKGKILVKGK------------- 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  481 evsdedsadeidddcklmngdasanrkrveniakkkldslikeskirdcedpnnftvstlpspgkaglksdskkskledd 560
Cdd:cd08632        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  561 vetgedfsaskrhsrslmgsfskrkkkgsklkkassleegeddsdsqgnlarssvhysrvnrqkktmKLSRALSDLVKYT 640
Cdd:cd08632    148 -------------------------------------------------------------------KLCRDLSDLVVYT 160

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  641 KSVGIHDVETElSSSWQVSSFSETKAHQILQQKPAQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVALNYQSE 720
Cdd:cd08632    161 NSVAAQDIVDD-GSTGNVLSFSETRAHQLVQQKAEQFMTYNQKQLTRIYPSAYRIDSSNFNPLPYWNVGCQLVALNYQSE 239

                          410
                   ....*....|....
gi 1799905226  721 GRMLQLNRAKFSAN 734
Cdd:cd08632    240 GRMMQLNRAKFMVN 253
PI-PLCc_eukaryota cd08558
Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; ...
 322-734 4.21e-118

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: 371.78  E-value: 4.21e-118
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  322 QDMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 401
Cdd:cd08558      2 QDMTQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGHTLTSKILFKDVIEAIKE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  402 YAFIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKLDLSSVHSDDSTkLPSPASLKGKILVKGKklpanisddaeege 481
Cdd:cd08558     82 YAFVTSPYPVILSLENHCSLEQQKKMAQILKEIFGDKLLTPPLDENPVQ-LPSPEQLKGKILIKGK-------------- 146

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  482 vsdedsadeidddcklmngdasanrkrveniakkkldslikeskirdcedpnnftvstlpspgkaglksdskkskleddv 561
Cdd:cd08558        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  562 etgedfsasKRHSRSLmgsfskrkkkgsklkkassleegeddsdsqgnlarssvhysrvnrqkktmklsralsdlvkytk 641
Cdd:cd08558    147 ---------KYHMSSF---------------------------------------------------------------- 153

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  642 svgihdvetelssswqvssfSETKAHQILQQKPAQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVALNYQSEG 721
Cdd:cd08558    154 --------------------SETKALKLLKESPEEFVKYNKRQLSRVYPKGTRVDSSNYNPQPFWNAGCQMVALNYQTPD 213

                          410
                   ....*....|...
gi 1799905226  722 RMLQLNRAKFSAN 734
Cdd:cd08558    214 LPMQLNQGKFEQN 226
PI-PLCc_delta cd08593
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily ...
 322-734 1.06e-106

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: 340.85  E-value: 1.06e-106
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  322 QDMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 401
Cdd:cd08593      2 QDMTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDGPDGEPIIYHGHTLTSKILFKDVIQAIRE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  402 YAFIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKLdLSSVHSDDSTKLPSPASLKGKILVKGKKLpanisddaeege 481
Cdd:cd08593     82 YAFKVSPYPVILSLENHCSVEQQKVMAQHLKSILGDKL-LTQPLDGVLTALPSPEELKGKILVKGKKL------------ 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  482 vsdedsadeidddcklmngdasanrkrveniakkkldslikeskirdcedpnnftvstlpspgkaglksdskkskleddv 561
Cdd:cd08593        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  562 etgedfsaskrhsrslmgsfskrkkkgsklkkassleegeddsdsqgnlarssvhysrvnrqkktmKLSRALSDLVKYTK 641
Cdd:cd08593    149 ------------------------------------------------------------------KLAKELSDLVIYCK 162

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  642 SVGIHDVET--ELSSSWQVSSFSETKAHQILQQKPAQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVALNYQS 719
Cdd:cd08593    163 SVHFKSFEHskENYHFYEMSSFSESKALKLAQESGNEFVRHNKRQLSRIYPAGLRTDSSNYDPQEMWNVGCQIVALNFQT 242

                          410
                   ....*....|....*
gi 1799905226  720 EGRMLQLNRAKFSAN 734
Cdd:cd08593    243 PGEEMDLNDGLFRQN 257
EFh_PI-PLCeta2 cd16221
EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also ...
 169-309 6.80e-98

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: 311.10  E-value: 6.80e-98
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  169 WLKQTFDEADKNGDGSLSISEVLQLMHKLNVNLPRQKVKQMFKEADTDANQGTLDFEEFCAFYKMMSTRRDLYLLMLTYS 248
Cdd:cd16221      1 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEADTDDNQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1799905226  249 NHKDYLDTDDLKRFLETEQKMTNVTKEHCLEIISKFEPCPENKKEGALGIDGFTNYMRSPS 309
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 ...
 169-309 2.57e-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: 306.23  E-value: 2.57e-96
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  169 WLKQTFDEADKNGDGSLSISEVLQLMHKLNVNLPRQKVKQMFKEADTDANQGTLDFEEFCAFYKMMSTRRDLYLLMLTYS 248
Cdd:cd16205      1 WLKQTFEEADKNGDGLLSIGEILQLMHKLNVNLPRRKVRQMFKEADTDDNQGTLDFEEFCAFYKMMSTRRELYLLLLSYS 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1799905226  249 NHKDYLDTDDLKRFLETEQKMTNVTKEHCLEIISKFEPCPENKKEGALGIDGFTNYMRSPS 309
Cdd:cd16205     81 NKKDYLTLEDLARFLEVEQKMTNVTLEYCLDIIEKFEPSEENKKNGLLGIDGFTNYMRSPA 141
PI-PLCc_PRIP_metazoa cd08597
Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This ...
 322-734 3.11e-89

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: 291.25  E-value: 3.11e-89
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  322 QDMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 401
Cdd:cd08597      2 QDMTQPLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDGPNGEPVIYHGHTLTSKISFRSVIEAINE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  402 YAFIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKLDLSSVHSDDStKLPSPASLKGKILVKGKKLpanisddaeege 481
Cdd:cd08597     82 YAFVASEYPLILCIENHCSEKQQLVMAQYLKEIFGDKLYTEPPNEGES-YLPSPHDLKGKIIIKGKKL------------ 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  482 vsdedsadeidddcklmngdasanrkrveniakkkldslikeskirdcedpnnftvstlpspgkaglksdskkskleddv 561
Cdd:cd08597        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  562 etgedfsaskrhsrslmgsfskrkkkgsklkkassleegeddsdsqgnlarssvhysrvnrqkKTMKLSRALSDLVKYTK 641
Cdd:cd08597    149 ---------------------------------------------------------------KRRKLCKELSDLVSLCK 165

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  642 SVGIHDVETELSSSW--QVSSFSETKAHQILQQKPAQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVALNYQS 719
Cdd:cd08597    166 SVRFQDFPTSAQNQKywEVCSFSENLARRLANEFPEDFVNYNKKFLSRVYPSPMRVDSSNYNPQDFWNCGCQIVAMNYQT 245

                          410
                   ....*....|....*
gi 1799905226  720 EGRMLQLNRAKFSAN 734
Cdd:cd08597    246 PGLMMDLNTGKFLEN 260
PI-PLCc_gamma cd08592
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...
 321-734 3.68e-86

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: 281.24  E-value: 3.68e-86
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  321 NQDMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 400
Cdd:cd08592      1 PQDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGPDGMPIIYHGHTLTSKIKFMDVLKTIK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  401 KYAFIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKLDLSSVhSDDSTKLPSPASLKGKILVKGKKLpanisddaeeg 480
Cdd:cd08592     81 EHAFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDMLLTQPV-DRNADQLPSPNQLKRKIIIKHKKL----------- 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  481 evsdedsadeidddcklmngdasanrkrveniakkkldslikeskirdcedpnnftvstlpspgkaglksdskkskledd 560
Cdd:cd08592        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  561 vetgedfsasKRHSRSLmgsfskrkkkgsklkkassleegeddsdsqgnlarssvhysrvnrqkktmklsralsdlvkyt 640
Cdd:cd08592    149 ----------FYEMSSF--------------------------------------------------------------- 155

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  641 ksvgihdvetelssswqvssfSETKAHQIL-QQKPAQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVALNYQS 719
Cdd:cd08592    156 ---------------------PETKAEKYLnRQKGKIFLKYNRRQLSRVYPKGQRVDSSNYDPVPMWNCGSQMVALNFQT 214

                          410
                   ....*....|....*
gi 1799905226  720 EGRMLQLNRAKFSAN 734
Cdd:cd08592    215 PDKPMQLNQALFMLN 229
PI-PLCc_delta4 cd08631
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily ...
 322-734 1.01e-83

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: 275.29  E-value: 1.01e-83
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  322 QDMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 401
Cdd:cd08631      2 QDMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDGPNGEPIVYHGHTFTSKILFKDVVAAVAQ 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  402 YAFIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKLDLSSVHSDDSTKLPSPASLKGKILVKGKKLpanisddaeege 481
Cdd:cd08631     82 YAFQVSDYPVILSLENHCGVEQQQTMAQHLTEILGEKLLSTTLDGVLPTQLPSPEELRGKILLKGKKI------------ 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  482 vsdedsadeidddcklmngdasanrkrveniakkkldslikeskirdcedpnnftvstlpspgkaglksdskkskleddv 561
Cdd:cd08631        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  562 etgedfsaskrhsrslmgsfskrkkkgsklkkassleegeddsdsqgnlarssvhysrvnrqkktmKLSRALSDLVKYTK 641
Cdd:cd08631    150 ------------------------------------------------------------------RLSPELSDCVIYCK 163

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  642 SVG--------IHDVETELssswqvSSFSETKAHQILQQKPAQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLV 713
Cdd:cd08631    164 SVSfrsfthsrEHYHFYEI------SSFTETKARKLIREAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQEMWNAGCQMV 237

                          410       420
                   ....*....|....*....|.
gi 1799905226  714 ALNYQSEGRMLQLNRAKFSAN 734
Cdd:cd08631    238 ALNFQTAGLEMDLNDGLFRQN 258
PI-PLC-X pfam00388
Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...
 324-466 3.06e-83

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: 268.99  E-value: 3.06e-83
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  324 MSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINKYA 403
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1799905226  404 FIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKLDLSSVHsDDSTKLPSPASLKGKILVKG 466
Cdd:pfam00388   81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLD-DDLTELPSPEDLKGKILIKG 142
PI-PLCc_beta cd08591
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ...
 322-734 3.69e-82

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily corresponds to the catalytic domain present in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-beta isozymes. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PLC-beta represents a class of mammalian PI-PLC that has an N-terminal pleckstrin homology (PH) domain, an array of EF hands, a PLC catalytic core domain, a C2 domain, and a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There are four PLC-beta isozymes (1-4). They are activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. The beta-gamma subunits of heterotrimeric G proteins are known to activate the PLC-beta2 and -beta3 isozymes only. Aside from four PLC-beta isozymes identified in mammals, some eukaryotic PLC-beta homologs have been classified into this subfamily, such as NorpA and PLC-21 from Drosophila and PLC-beta from turkey, Xenopus, sponge, and hydra.


Pssm-ID: 176533 [Multi-domain]  Cd Length: 257  Bit Score: 270.75  E-value: 3.69e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  322 QDMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDG--PDGEPIVHHGYTLTSKILFKDVIETI 399
Cdd:cd08591      2 QDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGkgEDEEPIITHGKTMCTEILFKDVIEAI 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  400 NKYAFIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKL---DLSSVHSDDSTKLPSPASLKGKILVKGKKlpanisdd 476
Cdd:cd08591     82 AETAFKTSEYPVILSFENHCSSKQQAKMAEYCREIFGDLLltePLEKYPLEPGVPLPSPNDLKRKILIKNKK-------- 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  477 aeegevsdedsadeidddcklmngdasanrkrveniakkkldslikeskirdcedpnnftvstlpspgkaglksdskksk 556
Cdd:cd08591        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  557 leddvetgedfsaskrhsrslmgsfskrkkkgsklkkassleegeddsdsqgnlarssvhysrvnrqkktmklsraLSDL 636
Cdd:cd08591    154 ----------------------------------------------------------------------------LSSL 157

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  637 VKYTKSVGIH--DVETELSSSWQVSSFSETKAHQILQQKPAQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVA 714
Cdd:cd08591    158 VNYIQPVKFQgfEVAEKRNKHYEMSSFNESKGLGYLKKSPIEFVNYNKRQLSRIYPKGTRVDSSNYMPQIFWNAGCQMVA 237

                          410       420
                   ....*....|....*....|
gi 1799905226  715 LNYQSEGRMLQLNRAKFSAN 734
Cdd:cd08591    238 LNFQTPDLPMQLNQGKFEYN 257
PI-PLCc_delta1 cd08629
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily ...
 322-734 6.72e-81

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: 267.29  E-value: 6.72e-81
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  322 QDMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 401
Cdd:cd08629      2 QDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVLRAIRD 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  402 YAFIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKLdLSSVHSDDSTKLPSPASLKGKILVKGKKLpanisddaeege 481
Cdd:cd08629     82 YAFKASPYPVILSLENHCSLEQQRVMARHLRAILGPIL-LDQPLDGVTTSLPSPEQLKGKILLKGKKL------------ 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  482 vsdedsadeidddcklmngdasanrkrveniakkkldslikeskirdcedpnnftvstlpspgkaglksdskkskleddv 561
Cdd:cd08629        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  562 etgedfsaskrhsrslmgsfskrkkkgsklkkassleegeddsdsqgnlarssvhysrvnrqkktmKLSRALSDLVKYTK 641
Cdd:cd08629    149 ------------------------------------------------------------------KLVPELSDMIIYCK 162

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  642 SV---GIHDVETELSSSWQVSSFSETKAHQILQQKPAQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVALNYQ 718
Cdd:cd08629    163 SVhfgGFSSPGTSGQAFYEMASFSESRALRLLQESGNGFVRHNVSCLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQ 242

                          410
                   ....*....|....*.
gi 1799905226  719 SEGRMLQLNRAKFSAN 734
Cdd:cd08629    243 TPGPEMDVYLGCFQDN 258
PI-PLC1c_yeast cd08598
Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This ...
 321-734 1.02e-76

Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This family corresponds to the catalytic domain present in a group of putative phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) encoded by PLC1 genes from yeasts, which are homologs of the delta isoforms of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The prototype of this CD is protein Plc1p encoded by PLC1 genes from Saccharomyces cerevisiae. Plc1p contains both highly conserved X- and Y- regions of PLC catalytic core domain, as well as a presumptive EF-hand like calcium binding motif. Experiments show that Plc1p displays calcium dependent catalytic properties with high similarity to those of the mammalian PLCs, and plays multiple roles in modulating the membrane/protein interactions in filamentation control. CaPlc1p encoded by CAPLC1 from the closely related yeast Candida albicans, an orthologue of S. cerevisiae Plc1p, is also included in this group. Like Plc1p, CaPlc1p has conserved presumptive catalytic domain, shows PLC activity when expressed in E. coli, and is involved in multiple cellular processes. There are two other gene copies of CAPLC1 in C. albicans, CAPLC2 (also named as PIPLC) and CAPLC3. Experiments show CaPlc1p is the only enzyme in C. albicans which functions as PLC. The biological functions of CAPLC2 and CAPLC3 gene products must be clearly different from CaPlc1p, but their exact roles remain unclear. Moreover, CAPLC2 and CAPLC3 gene products are more similar to extracellular bacterial PI-PLC than to the eukaryotic PI-PLC, and they are not included in this subfamily.


Pssm-ID: 176540 [Multi-domain]  Cd Length: 231  Bit Score: 254.09  E-value: 1.02e-76
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  321 NQDMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETIN 400
Cdd:cd08598      1 EEDLSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDGDDGEPVVTHGYTLTSSVPFRDVCRAIK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  401 KYAFIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKLdLSSVHSDDSTKLPSPASLKGKILVKGKklpanisddaeeg 480
Cdd:cd08598     81 KYAFVTSPYPLILSLEVHCDAEQQERMVEIMKETFGDLL-VTEPLDGLEDELPSPEELRGKILIKVK------------- 146

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  481 evsdedsadeidddcklmngdasanrkrveniakkkldsliKESKirdcedPNNFTvstlpspgkaglksdskkskledd 560
Cdd:cd08598    147 -----------------------------------------KESK------TPNHI------------------------ 155

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  561 vetgedFSASkrhsrslmgsfskrkkkgsklkkassleegeddsdsqgnlarssvhysrvnrqkktmklsralsdlvkyt 640
Cdd:cd08598    156 ------FSLS---------------------------------------------------------------------- 159

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  641 ksvgihdvetelssswqvssfsETKAHQILQQKPAQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVALNYQSE 720
Cdd:cd08598    160 ----------------------ERSLLKLLKDKRAALDKHNRRHLMRVYPSGTRISSSNFNPLPFWRAGVQMVALNWQTY 217

                          410
                   ....*....|....
gi 1799905226  721 GRMLQLNRAKFSAN 734
Cdd:cd08598    218 DLGMQLNEAMFAGS 231
PI-PLCc_zeta cd08595
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family ...
 322-734 2.14e-76

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family corresponds to the catalytic domain presenting in metazoan phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11)-zeta isozyme. PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. PI-PLC-zeta represents a class of sperm-specific PI-PLC that has an N-terminal EF-hand domain, a PLC catalytic core domain, and a C-terminal C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There is one PLC-zeta isozyme (1). PLC-zeta plays a fundamental role in vertebrate fertilization by initiating intracellular calcium oscillations that trigger the embryo development. However, the mechanism of its activation still remains unclear. Aside from PI-PLC-zeta identified in mammals, its eukaryotic homologs have been classified with this family.


Pssm-ID: 176537 [Multi-domain]  Cd Length: 257  Bit Score: 254.48  E-value: 2.14e-76
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  322 QDMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 401
Cdd:cd08595      2 QDMDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDGADNEPVVYHGYTLTSKILFKEVITTVEK 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  402 YAFIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKLDLSSVHSDDSTKLPSPASLKGKILVKGKKlpanisddaeege 481
Cdd:cd08595     82 YAFEKSDYPVVLSLENHCSTEQQEIMAHYLVSILGEKLLRAPIDDPATGELPSPEALKFKILVKNKK------------- 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  482 vsdedsadeidddcklmngdasanrkrveniakkkldslikeskirdcedpnnftvstlpspgkaglksdskkskleddv 561
Cdd:cd08595        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  562 etgedfsaskrhsrslmgsfskrkkkgsklkkassleegeddsdsqgnlarssvhysrvnrqkktmKLSRALSDLVKYTK 641
Cdd:cd08595    149 ------------------------------------------------------------------KIAKALSDLVIYTK 162

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  642 SVGIHDVETELSSSWQVSSFS--ETKAHQILQQKPAQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVALNYQS 719
Cdd:cd08595    163 SEKFCSFTHSRDNQHSYENNSigENKARKLLKSSGADFVGHTQRFITRIYPKGTRASSSNYNPQEFWNVGCQMVALNFQT 242

                          410
                   ....*....|....*
gi 1799905226  720 EGRMLQLNRAKFSAN 734
Cdd:cd08595    243 LGAPMDLQNGKFLDN 257
PI-PLCc_delta3 cd08630
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily ...
 322-734 5.98e-74

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: 247.24  E-value: 5.98e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  322 QDMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 401
Cdd:cd08630      2 QDMSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVIQAVRQ 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  402 YAFIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKLDLSSVHSDDSTKLPSPASLKGKILVKGKKLpanisddaeege 481
Cdd:cd08630     82 HAFTASPYPVILSLENHCGLEQQAAMARHLQTILGDMLVTQPLDSLNPEELPSPEELKGRVLVKGKKL------------ 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  482 vsdedsadeidddcklmngdasanrkrveniakkkldslikeskirdcedpnnftvstlpspgkaglksdskkskleddv 561
Cdd:cd08630        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  562 etgedfsaskrhsrslmgsfskrkkkgsklkkassleegeddsdsqgnlarssvhysrvnrqkktmKLSRALSDLVKYTK 641
Cdd:cd08630    150 ------------------------------------------------------------------QISPELSALAVYCQ 163

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  642 SVGIHDVET--ELSSSWQVSSFSETKAHQILQQKPAQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVALNYQS 719
Cdd:cd08630    164 ATRLRTLEPapVQPQPCQVSSLSERKAKKLIREAGNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLVALNFQT 243

                          410
                   ....*....|....*
gi 1799905226  720 EGRMLQLNRAKFSAN 734
Cdd:cd08630    244 PGYEMDLNAGRFLVN 258
EFh_PI-PLCeta1 cd16220
EF-hand motif found in phosphoinositide phospholipase C eta 1 (PI-PLC-eta1); PI-PLC-eta1, also ...
 169-309 1.73e-73

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: 241.08  E-value: 1.73e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  169 WLKQTFDEADKNGDGSLSISEVLQLMHKLNVNLPRQKVKQMFKEADTDANQGTLDFEEFCAFYKMMSTRRDLYLLMLTYS 248
Cdd:cd16220      1 WVKQTFEEADKNGDGLLNIEEIYQLMHKLNVNLPRRKVRQMFQEADTDENQGTLTFEEFCVFYKMMSLRRDLYLLLLSYS 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1799905226  249 NHKDYLDTDDLKRFLETEQKMTNVTKEHCLEIISKFEPCPENKKEGALGIDGFTNYMRSPS 309
Cdd:cd16220     81 DKKDHLTVEELAQFLKVEQKMNNVTTEYCLDIIKKFEVSEENKEQNVLGIEGFTNFMRSPA 141
PI-PLCc_gamma2 cd08628
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily ...
 322-734 5.96e-73

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: 244.19  E-value: 5.96e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  322 QDMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 401
Cdd:cd08628      2 QDMNNPLSHYWISSSHNTYLTGDQLRSESSTEAYIRCLRMGCRCIELDCWDGPDGKPIIYHGWTRTTKIKFDDVVQAIKD 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  402 YAFIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKLDLSSVHSdDSTKLPSPASLKGKILVKGKKLPANisddaeegE 481
Cdd:cd08628     82 HAFVTSEYPVILSIEEHCSVEQQRHMAKVFKEVFGDKLLMKPLEA-SADQLPSPTQLKEKIIIKHKKLIAI--------E 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  482 VSDedsadeidddcklmngdasanrkrveniakkkldslikeskirdcedpnnFTVSTLPSpgkaglksdskkSKLEDDV 561
Cdd:cd08628    153 LSD--------------------------------------------------LVVYCKPT------------SKTKDNL 170

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  562 ETgEDFsaskRHSRSLMgsfskrkkkgsklkkassleegeddsdsqgnlarssvhysrvnrqkktmklsralsdlvkytk 641
Cdd:cd08628    171 EN-PDF----KEIRSFV--------------------------------------------------------------- 182

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  642 svgihdvetelssswqvssfsETKAHQILQQKPAQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVALNYQSEG 721
Cdd:cd08628    183 ---------------------ETKAPSIIRQKPVQLLKYNRKGLTRVYPKGQRVDSSNYDPFRLWLCGSQMVALNFQTAD 241

                          410
                   ....*....|...
gi 1799905226  722 RMLQLNRAKFSAN 734
Cdd:cd08628    242 KYMQLNHALFSLN 254
PI-PLCc_epsilon cd08596
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ...
 322-734 3.85e-67

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: 227.42  E-value: 3.85e-67
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  322 QDMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 401
Cdd:cd08596      2 EDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGDDGMPIIYHGHTLTTKIPFKDVVEAINR 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  402 YAFIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKLD---LSSVHSDDSTKLPSPASLKGKILVKGKKLPanisddae 478
Cdd:cd08596     82 SAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLVtkfLFESDFSDDPSLPSPLQLKNKILLKNKKAP-------- 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  479 egEVSDedsadeidddcklmngdasanrkrveniakkkLDSLIKESKIRDcedpnnftvstLPSPgkaglksdskkskle 558
Cdd:cd08596    154 --ELSD--------------------------------LVIYCQAVKFPG-----------LSTP--------------- 173

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  559 ddvetgedfsaskrhsrslmgsfskrkkkgsklkkassleegeddsdsqgnlarSSVHYSRVNrqkktmklsralsdlvk 638
Cdd:cd08596    174 ------------------------------------------------------KCYHISSLN----------------- 182

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  639 ytksvgihdvetelssswqvssfsETKAHQILQQKPAQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVALNYQ 718
Cdd:cd08596    183 ------------------------ENAAKRLCRRYPQKLVQHTRCQLLRTYPAATRIDSSNPNPLIFWLHGLQLVALNYQ 238

                          410
                   ....*....|....*.
gi 1799905226  719 SEGRMLQLNRAKFSAN 734
Cdd:cd08596    239 TDDLPMHLNAAMFEAN 254
PI-PLCc_beta4 cd08626
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily ...
 322-734 1.59e-66

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: 225.80  E-value: 1.59e-66
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  322 QDMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGP--DGEPIVHHGYTLTSKILFKDVIETI 399
Cdd:cd08626      2 QDMDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGKgeDQEPIITHGKAMCTDILFKDVIQAI 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  400 NKYAFIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKL---DLSSVHSDDSTKLPSPASLKGKILVKGKKlpanisdd 476
Cdd:cd08626     82 KDTAFVTSDYPVILSFENHCSKPQQYKLAKYCEEIFGDLLltkPLESHPLEPGVPLPSPNKLKRKILIKNKR-------- 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  477 aeegevsdedsadeidddcklmngdasanrkrveniakkkldslikeskirdcedpnnftvstlpspgkaglksdskksk 556
Cdd:cd08626        --------------------------------------------------------------------------------

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  557 leddvetgedfsaskrhsrslmgsfskrkkkgsklkkassleegeddsdsqgnlarssvhysrvnrqkktmklsraLSDL 636
Cdd:cd08626    154 ----------------------------------------------------------------------------LSSL 157

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  637 VKYTKSVGIH--DVETELSSSWQVSSFSETKAHQILQQKPAQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVA 714
Cdd:cd08626    158 VNYAQPVKFQgfDVAEERNIHFNMSSFNESVGLGYLKTSAIEFVNYNKRQMSRIYPKGTRVDSSNYMPQIFWNAGCQMVS 237

                          410       420
                   ....*....|....*....|
gi 1799905226  715 LNYQSEGRMLQLNRAKFSAN 734
Cdd:cd08626    238 LNFQTPDLGMQLNQGKFEYN 257
PI-PLCc_gamma1 cd08627
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily ...
 322-734 6.90e-65

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: 220.29  E-value: 6.90e-65
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  322 QDMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 401
Cdd:cd08627      2 EEMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  402 YAFIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKLdLSSVHSDDSTKLPSPASLKGKILVKGKKLpanisddaeege 481
Cdd:cd08627     82 HAFVTSEYPIILSIEDHCSIVQQRNMAQHFKKVFGDML-LTKPVDINADGLPSPNQLKRKILIKHKKL------------ 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  482 vsdedsadeidddcklmngdasanrkrveniakkkldslikeskIRDcedpnnftVSTLPspgkaglksdskkskleddv 561
Cdd:cd08627    149 --------------------------------------------YRD--------MSSFP-------------------- 156

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  562 etgedfsaskrhsrslmgsfskrkkkgsklkkassleegeddsdsqgnlarssvhysrvnrqkktmklsralsdlvkytk 641
Cdd:cd08627        --------------------------------------------------------------------------------

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  642 svgihdvetelssswqvssfsETKAHQILQQ-KPAQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVALNYQSE 720
Cdd:cd08627    157 ---------------------ETKAEKYVNRsKGKKFLQYNRRQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTP 215

                          410
                   ....*....|....
gi 1799905226  721 GRMLQLNRAKFSAN 734
Cdd:cd08627    216 DKPMQMNQALFMLG 229
PI-PLCc_beta2 cd08624
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily ...
 322-734 5.11e-64

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: 218.77  E-value: 5.11e-64
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  322 QDMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDG--PDGEPIVHHGYTLTSKILFKDVIETI 399
Cdd:cd08624      2 QDMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTEILFKDAIEAI 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  400 NKYAFIKNEYPVILSIENHC-SIVQQKKMAQYLTEILGDKL---DLSSVHSDDSTKLPSPASLKGKILVKGKKLPANISd 475
Cdd:cd08624     82 AESAFKTSPYPVILSFENHVdSPKQQAKMAEYCRTIFGDMLltePLEKYPLKPGVPLPSPEDLRGKILIKNKKYEEMSS- 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  476 daeegevsdedsadeidddcklmngdasanrkRVENIAKKKLDSLikeskirdcedpnnftvstlpspgkaglksdskks 555
Cdd:cd08624    161 --------------------------------LVNYIQPTKFVSF----------------------------------- 173

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  556 kleddvetgeDFSASKrhsrslmgsfskrkkkgsklkkassleegeddsdsqgnlarssvhysrvNRqkktmklSRALSD 635
Cdd:cd08624    174 ----------EFSAQK-------------------------------------------------NR-------SYVISS 187

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  636 LVkytksvgihdvetelssswqvssfsETKAHQILQQKPAQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVAL 715
Cdd:cd08624    188 FT-------------------------ELKAYDLLSKASVQFVEYNKRQMSRIYPKGTRMDSSNYMPQMFWNVGCQMVAL 242

                          410
                   ....*....|....*....
gi 1799905226  716 NYQSEGRMLQLNRAKFSAN 734
Cdd:cd08624    243 NFQTMDLPMQQNMALFEFN 261
PLCXc smart00148
Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...
 324-467 1.94e-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: 212.53  E-value: 1.94e-63
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226   324 MSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINKYA 403
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1799905226   404 FIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKLDLSSVHSdDSTKLPSPASLKGKILVKGK 467
Cdd:smart00148   81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTS-SLEVLPSPEQLRGKILLKVR 143
PLN02952 PLN02952
phosphoinositide phospholipase C
 211-874 2.52e-61

phosphoinositide phospholipase C


Pssm-ID: 178538 [Multi-domain]  Cd Length: 599  Bit Score: 222.18  E-value: 2.52e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  211 KEADTDANQGTLDFEEFCAF---YKMMSTR--RDLYLLMLTYSNHKDYLDTDDLKRFLETEQKMTNVT----KEHCLEII 281
Cdd:PLN02952     6 KTESYNNDSGSYNYKMFNLFnrkFKITEAEppDDVKDVFCKFSVGGGHMGADQLRRFLVLHQDELDCTlaeaQRIVEEVI 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  282 SKFEPCPENKKEGaLGIDGFTNYMRSPsgDIFNPEHYQVNQDMSYPLSHYFITSSHNTYLMGDQLMSQ-SRVDMYAwVLQ 360
Cdd:PLN02952    86 NRRHHVTRYTRHG-LNLDDFFHFLLYD--DLNGPITPQVHHDMTAPLSHYFIYTGHNSYLTGNQLSSDcSEVPIVK-ALQ 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  361 SGCRCVEVDCWDGPDGEPI-VHHGYTLTSKILFKDVIETINKYAFIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKL 439
Cdd:PLN02952   162 RGVRVIELDLWPGSTKDEIlVLHGRTLTTPVPLIKCLKSIRDYAFSSSPYPVIITLEDHLTPDLQAKVAEMATQIFGQML 241

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  440 DLSsvHSDDSTKLPSPASLKGKILVKGKklPANisddaeegevsdedsadeidddcKLMNGDASANRKRVENIAKKKlds 519
Cdd:PLN02952   242 YYP--ESDSLVQFPSPESLKHRIIISTK--PPK-----------------------EYLESSGPIVIKKKNNVSPSG--- 291

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  520 liKESKIRDCEdpnnftVSTLPSPgKAGLKSDSKKSKLEDDVETGEDfsASKRHSRSLmgsfskrkkkgsklkkasslee 599
Cdd:PLN02952   292 --RNSSEETEE------AQTLESM-LFEQEADSRSDSDQDDNKSGEL--QKPAYKRLI---------------------- 338

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  600 geddsdsqgnlarsSVHysrVNRQKKTMKlsRALSDLVKYTKSVGIHDVETElssswqvsSFSETKAHQIlqqkpaqyLR 679
Cdd:PLN02952   339 --------------TIH---AGKPKGTLK--DAMKVAVDKVRRLSLSEQELE--------KAATTNGQDV--------VR 383

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  680 FNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVALNYQSEGRMLQLNRAKFSANGNCGYVLKPNCMCQGVFNPNSEDP- 758
Cdd:PLN02952   384 FTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSLWLMHGMFRANGGCGYLKKPDFLMKKGFHDEVFDPk 463

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  759 --LPgqLKKQLVLRIISGQQLPKPRDSMLGDRGEIIDPFVEVEVIGLPVDCFKEQTRVVDDNgFNPMWEETLVFTVHMPE 836
Cdd:PLN02952   464 kkLP--VKKTLKVKVYLGDGWRLDFSHTHFDSYSPPDFYTKMYIVGVPADNAKKKTKIIEDN-WYPAWNEEFSFPLTVPE 540

                          650       660       670
                   ....*....|....*....|....*....|....*....
gi 1799905226  837 IALIRFLVWDHDPIGR-DFIGQRTIAFSSMMPGYRHVYL 874
Cdd:PLN02952   541 LALLRIEVREYDMSEKdDFGGQTCLPVSELRPGIRSVPL 579
PI-PLCc_beta3 cd08625
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily ...
 323-734 1.53e-58

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: 202.98  E-value: 1.53e-58
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  323 DMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDG--PDGEPIVHHGYTLTSKILFKDVIETIN 400
Cdd:cd08625      3 DMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGrpPEEEPFITHGFTMTTEIPFKDVIEAIA 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  401 KYAFIKNEYPVILSIENHC-SIVQQKKMAQYLTEILGDKLDLSSVHS---DDSTKLPSPASLKGKILVKGKKLPAnisdd 476
Cdd:cd08625     83 ESAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDKyplVPGVQLPSPQELMGKILVKNKKMST----- 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  477 aeegevsdedsadeidddckLMNgdasanrkRVENIAKKKLDslikeskirdcedpnnftvstlpspgkaglksdskksk 556
Cdd:cd08625    158 --------------------LVN--------YIEPVKFKSFE-------------------------------------- 171

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  557 leddvetgedfSASKRhsrslmgsfskrkkkgsklkkassleegeddsdsqgnlarssvhysrvnrqKKTMKLSRALsdl 636
Cdd:cd08625    172 -----------AAAKR---------------------------------------------------NKFFEMSSFV--- 186

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  637 vkytksvgihdvetelssswqvssfsETKAHQILQQKPAQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVALN 716
Cdd:cd08625    187 --------------------------ETKAMEQLTKSPMEFVEYNKKQLSRIYPKGTRVDSSNYMPQLFWNVGCQMVALN 240

                          410
                   ....*....|....*...
gi 1799905226  717 YQSEGRMLQLNRAKFSAN 734
Cdd:cd08625    241 FQTLDLAMQLNMGVFEYN 258
PLN02228 PLN02228
Phosphoinositide phospholipase C
 243-874 2.53e-57

Phosphoinositide phospholipase C


Pssm-ID: 177873 [Multi-domain]  Cd Length: 567  Bit Score: 209.51  E-value: 2.53e-57
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  243 LMLTYSnHKDYLDTDDLKRFLETEQKMTNVTKEHCLEIISKFEPCPENKKEGALGIDGFTNYMRSPSGDIFnPEHYQVNQ 322
Cdd:PLN02228    29 LFEAYS-RNGKMSFDELLRFVSEVQGERHAGLDYVQDIFHSVKHHNVFHHHGLVHLNAFYRYLFSDTNSPL-PMSGQVHH 106

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  323 DMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGPDG-EPIVHHGYTLTSKILFKDVIETINK 401
Cdd:PLN02228   107 DMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSGnAAEVRHGRTLTSHEDLQKCLNAIKD 186

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  402 YAFIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKLDLSSvhsDDSTK-LPSPASLKGKILVKGKklpanisddaeeg 480
Cdd:PLN02228   187 NAFQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGMLFRCT---SESTKhFPSPEELKNKILISTK------------- 250

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  481 evsdedsadeidddcklmngdasanrkrveniakkkldslikeskirdcedpnnftvstlpsPGKAGLKSDSKKSKLEDD 560
Cdd:PLN02228   251 --------------------------------------------------------------PPKEYLESKTVQTTRTPT 268

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  561 VETgedfSASKRHSRSlmgsfskrkkkgsklKKASSLEEGEDDSDSQGNLARSSVHYSrvNRQKKtmkLSRALSDLVKYT 640
Cdd:PLN02228   269 VKE----TSWKRVADA---------------ENKILEEYKDEESEAVGYRDLIAIHAA--NCKDP---LKDCLSDDPEKP 324

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  641 KSVGIhdvetelssswqvssfSETKAHQILQQKPAQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVALNYQSE 720
Cdd:PLN02228   325 IRVSM----------------DEQWLETMVRTRGTDLVRFTQRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFNMQGH 388

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  721 GRMLQLNRAKFSANGNCGYVLKPNCMCQ--GVFNPNSEDPLPGQLKkqlvLRIISGQ--QLPKPRDSMlgDRGEIIDPFV 796
Cdd:PLN02228   389 GKQLWIMQGMFRANGGCGYVKKPRILLDehTLFDPCKRLPIKTTLK----VKIYTGEgwDLDFHLTHF--DQYSPPDFFV 462

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  797 EVEVIGLPVDCFKEQTRVVDDNGFnPMW-EETLVFTVHMPEIALIRFLVWDHDP-IGRDFIGQRTIAFSSMMPGYRHVYL 874
Cdd:PLN02228   463 KIGIAGVPRDTVSYRTETAVDQWF-PIWgNDEFLFQLRVPELALLWFKVQDYDNdTQNDFAGQTCLPLPELKSGVRAVRL 541
PLN02222 PLN02222
phosphoinositide phospholipase C 2
 238-874 1.62e-56

phosphoinositide phospholipase C 2


Pssm-ID: 177868 [Multi-domain]  Cd Length: 581  Bit Score: 207.57  E-value: 1.62e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  238 RDLYLLMLTYSNhKDYLDTDDLKRFLETEQKMTNVTKEHCLEIISKFEPCPEnkkEGALGIDGFTNYMrspSGDIFNP-E 316
Cdd:PLN02222    25 REIKTIFEKYSE-NGVMTVDHLHRFLIDVQKQDKATREDAQSIINSASSLLH---RNGLHLDAFFKYL---FGDNNPPlA 97

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  317 HYQVNQDMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGPDGEPI-VHHGYTLTSKILFKDV 395
Cdd:PLN02222    98 LHEVHHDMDAPISHYFIFTGHNSYLTGNQLSSDCSEVPIIDALKKGVRVIELDIWPNSDKDDIdVLHGMTLTTPVGLIKC 177

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  396 IETINKYAFIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKLdLSSVHSDDSTKLPSPASLKGKILVKGKKlpanisd 475
Cdd:PLN02222   178 LKAIRAHAFDVSDYPVVVTLEDHLTPDLQSKVAEMVTEIFGEIL-FTPPVGESLKEFPSPNSLKKRIIISTKP------- 249

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  476 DAEEGEVSDedsaDEIDDDCKLMnGDasanrkrvENIAKKKLDSLIKESKIRDcedpnnftvstlpspgkaglKSDSKKS 555
Cdd:PLN02222   250 PKEYKEGKD----DEVVQKGKDL-GD--------EEVWGREVPSFIQRNKSVD--------------------KNDSNGD 296

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  556 KLEDDvetgedfsaskrhsrslmgsfskrkkkgsklkkassleeGEDDSDSQGNLARSSVHYSRVNRQKKTMKLSRALSD 635
Cdd:PLN02222   297 DDDDD---------------------------------------DDGEDKSKKNAPPQYKHLIAIHAGKPKGGITECLKV 337

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  636 LVKYTKSVGIHDVETElssswqvsSFSETKAHQILqqkpaqylRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVAL 715
Cdd:PLN02222   338 DPDKVRRLSLSEEQLE--------KAAEKYAKQIV--------RFTQHNLLRIYPKGTRVTSSNYNPLVGWSHGAQMVAF 401

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  716 NYQSEGRMLQLNRAKFSANGNCGYVLKPNCMCQG-----VFNPNSEDPLPGQLKkqLVLRIISGQQLPKPRDSMlgDRGE 790
Cdd:PLN02222   402 NMQGYGRSLWLMQGMFRANGGCGYIKKPDLLLKSgsdsdIFDPKATLPVKTTLR--VTIYMGEGWYFDFRHTHF--DQYS 477

                          570       580       590       600       610       620       630       640
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  791 IIDPFVEVEVIGLPVDCFKEQTRVVDDNgFNPMWEETLVFTVHMPEIALIRFLVWDHDPIGR-DFIGQRTIAFSSMMPGY 869
Cdd:PLN02222   478 PPDFYTRVGIAGVPGDTVMKKTKTLEDN-WIPAWDEVFEFPLTVPELALLRLEVHEYDMSEKdDFGGQTCLPVWELSQGI 556


                   ....*
gi 1799905226  870 RHVYL 874
Cdd:PLN02222   557 RAFPL 561
PI-PLCc_beta1 cd08623
Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily ...
 321-734 6.65e-55

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: 192.61  E-value: 6.65e-55
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  321 NQDMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDG--PDGEPIVHHGYTLTSKILFKDVIET 398
Cdd:cd08623      1 NEDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGrtAEEEPVITHGFTMTTEISFKEVIEA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  399 INKYAFIKNEYPVILSIENHC-SIVQQKKMAQYLTEILGDKLDLSSVHS---DDSTKLPSPASLKGKILVKGKKLpanis 474
Cdd:cd08623     81 IAECAFKTSPFPILLSFENHVdSPKQQAKMAEYCRLIFGDALLMEPLEKyplESGVPLPSPMDLMYKILVKNKKM----- 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  475 ddaeegevsdedsadeidddcklmngdasanrkrveniakkkldslikeskirdcedpNNFTVSTLPspgkagLKSDSkk 554
Cdd:cd08623    156 ----------------------------------------------------------SNLVNYIQP------VKFES-- 169

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  555 skleddvetgedFSASKRHSRSLmgsfskrkkkgsklkkassleegeddsdsqgnlarssvhysrvnrqkktmklsrALS 634
Cdd:cd08623    170 ------------FEASKKRNKSF------------------------------------------------------EMS 183

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  635 DLVkytksvgihdvetelssswqvssfsETKAHQILQQKPAQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVA 714
Cdd:cd08623    184 SFV-------------------------ETKGLEQLTKSPVEFVEYNKMQLSRIYPKGTRVDSSNYMPQLFWNAGCQMVA 238

                          410       420
                   ....*....|....*....|
gi 1799905226  715 LNYQSEGRMLQLNRAKFSAN 734
Cdd:cd08623    239 LNFQTVDLSMQINMGMYEYN 258
PH_PLC_eta cd13364
Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of ...
 45-151 1.29e-53

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: 182.87  E-value: 1.29e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226   45 MQMGTQMIKLRGGSKGLVRFYYLDDHRSCIRWRPSRKN-EKAKISIDSIQEVCEGKQSEIFQRY-ADGSFDPNCCFSIYY 122
Cdd:cd13364      1 MQEGSELVKVRSNSRQYRRFFYLDEDKSSIRWKPSKKKsEKAKIPISSIREVREGKTTDIFRSCdISGDFPEECCFSIIY 80

                           90       100
                   ....*....|....*....|....*....
gi 1799905226  123 GDHMESLDLVSSSAEEARTWITGLKYLMA 151
Cdd:cd13364     81 GEEYETLDLVASSPDEANIWITGLRYLMS 109
C2_PLC_like cd00275
C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...
 764-888 3.88e-53

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: 182.36  E-value: 3.88e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  764 KKQLVLRIISGQQLPKPRDsmlgDRGEIIDPFVEVEVIGLPV-DCFKEQTRVVDDNGFNPMWEETLVFTVHMPEIALIRF 842
Cdd:cd00275      1 PLTLTIKIISGQQLPKPKG----DKGSIVDPYVEVEIHGLPAdDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRF 76

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1799905226  843 LVWDHDPIGRDFIGQRTIAFSSMMPGYRHVYL-----EGIEEASIFVHVAI 888
Cdd:cd00275     77 VVYDEDSGDDDFLGQACLPLDSLRQGYRHVPLldskgEPLELSTLFVHIDI 127
EFh_PRIP cd16206
EF-hand motif found in phospholipase C-related but catalytically inactive proteins (PRIP); ...
 169-308 4.26e-53

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: 182.80  E-value: 4.26e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  169 WLKQTFDEADKNGDGSLSISEVLQLMHKLNVNLPRQKVKQMFKE--ADTDANQGTLDFEEFCAFYKMMSTRRDLYLLMLT 246
Cdd:cd16206      1 WLESVFEEADTNKSGFLDEEEAVQLIKQLNPGLSTSRIKQKLKElqKKKDGARGRVSSDEFVELFKELATRPEIYFLLVR 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1799905226  247 YSNHKDYLDTDDLKRFLETEQKMTNVTKEHCLEIISKFEPCPENKKEGALGIDGFTNYMRSP 308
Cdd:cd16206     81 YASNKDYLTVDDLMLFLEAEQGMTGVTKEKCLEIINKYEPSEEGREKGQLGIDGFTRYLLSE 142
PI-PLCc_plant cd08599
Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family ...
 322-492 3.22e-52

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: 183.73  E-value: 3.22e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  322 QDMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 401
Cdd:cd08599      2 HDMTAPLSHYFIFSSHNSYLTGNQLSSRSSTAPIIEALLRGCRVIELDLWPGGRGDICVLHGGTLTKPVKFEDCIKAIKE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  402 YAFIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKLDLSsvHSDDSTK-LPSPASLKGKILV--KGKKLPANISDDAE 478
Cdd:cd08599     82 NAFTASEYPVIITLENHLSPELQAKAAQILRETLGDKLFYP--DSEDLPEeFPSPEELKGKILIsdKPPVIRNSLSETQL 159

                          170
                   ....*....|....
gi 1799905226  479 EGEVSDEDSADEID 492
Cdd:cd08599    160 KKVIEGEHPTDLIE 173
PLN02230 PLN02230
phosphoinositide phospholipase C 4
 296-874 1.29e-51

phosphoinositide phospholipase C 4


Pssm-ID: 177875 [Multi-domain]  Cd Length: 598  Bit Score: 193.38  E-value: 1.29e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  296 LGIDGFTNYMRSPsgDIFNPEHYQVNQDMSYPLSHYFITSSHNTYLMGDQLMSQSRVDMYAWVLQSGCRCVEVDCWDGPD 375
Cdd:PLN02230    91 LTLDDFNYYLFST--DLNPPIADQVHQNMDAPLSHYFIFTGHNSYLTGNQLSSNCSELPIADALRRGVRVVELDLWPRGT 168

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  376 GEPIVHHGYTLTSKILFKDVIETINKYAFIKNEYPVILSIENHCSIVQQKKMAQYLTEILGDKLDLSSvhSDDSTKLPSP 455
Cdd:PLN02230   169 DDVCVKHGRTLTKEVKLGKCLDSIKANAFAISKYPVIITLEDHLTPKLQFKVAKMITQTFGDMLYYHD--SEGCQEFPSP 246

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  456 ASLKGKILVKGKK----LPANIS---DDAEEGEVSDEDsadeidddcklmngdasanrkrvenIAKKKLDSLIkeskird 528
Cdd:PLN02230   247 EELKEKILISTKPpkeyLEANDAkekDNGEKGKDSDED-------------------------VWGKEPEDLI------- 294

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  529 cedpnnftvstlpspgkaglksdSKKSKLEDDVETGEDFSASKRhsrslmgsfskrkkkgsklkkasslEEGEDDSDSQG 608
Cdd:PLN02230   295 -----------------------STQSDLDKVTSSVNDLNQDDE-------------------------ERGSCESDTSC 326

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  609 NLarSSVHYSR---VNRQKKTMKLSRALSDLVKYTKSVGIhdvetelssswqvssfsetkAHQILQQKPAQY----LRFN 681
Cdd:PLN02230   327 QL--QAPEYKRliaIHAGKPKGGLRMALKVDPNKIRRLSL--------------------SEQLLEKAVASYgadvIRFT 384

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  682 QHQLSRIYPSSYRVDSSNYNPQPFWNAGCQLVALNYQSEGRMLQLNRAKFSANGNCGYVLKPNCMC------QGVFNPNS 755
Cdd:PLN02230   385 QKNFLRIYPKGTRFNSSNYKPQIGWMSGAQMIAFNMQGYGRALWLMEGMFRANGGCGYVKKPDFLMdagpngQDFYPKDN 464

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  756 EDPlpgqlKKQLVLRIISGQQLPKPRDSMLGDRGEIIDPFVEVEVIGLPVDCFKEQTRVVDDNgFNPMWEETLVFTVHMP 835
Cdd:PLN02230   465 SCP-----KKTLKVKVCMGDGWLLDFKKTHFDSYSPPDFFVRVGIAGAPVDEVMEKTKIEYDT-WTPIWNKEFIFPLAVP 538

                          570       580       590       600
                   ....*....|....*....|....*....|....*....|
gi 1799905226  836 EIALIRFLVWDHDPIGR-DFIGQRTIAFSSMMPGYRHVYL 874
Cdd:PLN02230   539 ELALLRVEVHEHDINEKdDFGGQTCLPVSEIRQGIHAVPL 578
PI-PLC-Y pfam00387
Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to ...
 633-745 1.45e-49

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


Pssm-ID: 459794  Cd Length: 114  Bit Score: 171.49  E-value: 1.45e-49
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  633 LSDLVKYTKSVGIHDVETELSSSWQVSSF-SETKAHQILQQKPAQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQ 711
Cdd:pfam00387    1 LSDLVVYTQSVKFKSFSTPESKTPNHIFSfSESKALKLIKSSSAAFVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNCGVQ 80

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1799905226  712 LVALNYQSEGRMLQLNRAKFSANGNCGYVLKPNC 745
Cdd:pfam00387   81 MVALNWQTPDEGMQLNEGMFADNGGCGYVLKPEF 114
EFh_PI-PLCdelta cd16202
EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta ...
 169-308 3.97e-45

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: 159.70  E-value: 3.97e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  169 WLKQTFDEADKNGDGSLSISEVLQLMHKLNVNLPRQKVKQMFKEADTDANQgTLDFEEFCAFYKMMSTRRDLYLLMLTYS 248
Cdd:cd16202      1 WLKDQFRKADKNGDGKLSFKECKKLLKKLNVKVDKDYAKKLFQEADTSGED-VLDEEEFVQFYNRLTKRPEIEELFKKYS 79

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  249 NHKDYLDTDDLKRFLETEQKMTNVTKEHCLEIISKFEPCPENKKEGALGIDGFTNYMRSP 308
Cdd:cd16202     80 GDDEALTVEELRRFLQEEQKVKDVTLEWAEQLIETYEPSEDLKAQGLMSLDGFTLFLLSP 139
PLCYc smart00149
Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ...
 634-746 1.08e-44

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: 157.79  E-value: 1.08e-44
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226   634 SDLVKYTKSVGIHDVETELSSSWQVSSF--SETKAHQILQQKPAQYLRFNQHQLSRIYPSSYRVDSSNYNPQPFWNAGCQ 711
Cdd:smart00149    1 SDLVIYCAPVKFRSFESAESKNPFYEMSsfSETKAKKLLKKSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGCQ 80

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 1799905226   712 LVALNYQSEGRMLQLNRAKFSANGNCGYVLKPNCM 746
Cdd:smart00149   81 MVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115
PI-PLCc cd00137
Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This ...
 322-472 1.91e-44

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: 163.20  E-value: 1.91e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  322 QDMSYPLSHYFITSSHNTYLMGDQL-----MSQSRVDMYAWVLQSGCRCVEVDCWDGPDGEPIVHHGYTLTsKILFKDVI 396
Cdd:cd00137      2 HPDTQPLAHYSIPGTHDTYLTAGQFtikqvWGLTQTEMYRQQLLSGCRCVDIRCWDGKPEEPIIYHGPTFL-DIFLKEVI 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1799905226  397 ETINKYAFIKNEYPVILSIENHCSIV--QQKKMAQYLTEILGDKldLSSVHSDDSTKLPSPASLKGKILVKGKKLPAN 472
Cdd:cd00137     81 EAIAQFLKKNPPETIIMSLKNEVDSMdsFQAKMAEYCRTIFGDM--LLTPPLKPTVPLPSLEDLRGKILLLNKKNGFS 156
EFh_PI-PLC cd15898
EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...
 169-308 9.99e-42

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: 150.13  E-value: 9.99e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  169 WLKQTFDEADKNGDGSLSISEVLQLMHKLNVNLPRQKVKQMFKEADTDaNQGTLDFEEFCAFYKMMSTRRDLYLLMLTY- 247
Cdd:cd15898      1 WLRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVDTN-GDGTLTFDEFEELYKSLTERPELEPIFKKYa 79

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1799905226  248 SNHKDYLDTDDLKRFLETEQKMtNVTKEHCLEIISKFEPCPENKKegaLGIDGFTNYMRSP 308
Cdd:cd15898     80 GTNRDYMTLEEFIRFLREEQGE-NVSEEECEELIEKYEPERENRQ---LSFEGFTNFLLSP 136
PH_PLC_ELMO1 cd01248
Phospholipase C and Engulfment and cell motility protein 1 pleckstrin homology domain; The ...
 45-150 7.77e-36

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: 132.06  E-value: 7.77e-36
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226   45 MQMGTQMIKLRGGSKGLVRFYYLDDHRSCIRWRPSRK-NEKAKISIDSIQEVCEGKQSEIFQRY-ADGSFDPNCCFSIYY 122
Cdd:cd01248      1 LQQGTLLLKYREGSKPKERTFYLDPDGTRITWESSKKkSEKKSIDISDIKEIRPGKDTDGFKRKkKSNKPKEERCFSIIY 80

                           90       100
                   ....*....|....*....|....*...
gi 1799905226  123 GDHMESLDLVSSSAEEARTWITGLKYLM 150
Cdd:cd01248     81 GSNNKTLDLVAPSEDEANLWVEGLRALL 108
EFh_PRIP1 cd16222
EF-hand motif found in phospholipase C-related but catalytically inactive protein 1 (PRIP-1); ...
 169-308 3.82e-32

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: 123.05  E-value: 3.82e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  169 WLKQTFDEADKNGDGSLSISEVLQLMHKLNVNLPRQKVKQMFKEADTDANQGT--LDFEEFCAFYKMMSTRRDLYLLMLT 246
Cdd:cd16222      1 WLSAVFEAADVDGYGIMLEDTAVELIKQLNPGIKEAKIRLKFKEIQKSKEKLTtrVTEEEFCEAYSELCTRPEVYFLLVQ 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1799905226  247 YSNHKDYLDTDDLKRFLETEQKMTNVTKEHCLEIISKFEPCPENKKEGALGIDGFTNYMRSP 308
Cdd:cd16222     81 ISKNKEYLDAKDLMLFLEAEQGMTHITEEMCLDIIRRYEPSQEGRLKGFLGIDGFTQYLLSS 142
EFh_PRIP2 cd16223
EF-hand motif found in phospholipase C-related but catalytically inactive protein 2 (PRIP-2); ...
 169-308 4.84e-31

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: 119.63  E-value: 4.84e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  169 WLKQTFDEADKNGDGSLSISEVLQLMHKLNVNLPRQKVKQMFKEADTDANQGTLDF--EEFCAFYKMMSTRRDLYLLMLT 246
Cdd:cd16223      1 WLSQMFVEADTDNVGHITLCRAVQFIKNLNPGLKTSKIELKFKELHKSKEKGGTEVtkEEFIEVFHELCTRPEIYFLLVQ 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1799905226  247 YSNHKDYLDTDDLKRFLETEQKMTNVTKEHCLEIISKFEPCPENKKEGALGIDGFTNYMRSP 308
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, ...
 169-308 3.55e-28

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: 111.47  E-value: 3.55e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  169 WLKQTFDEADKNGDGSLSISEVLQLMHKLNVNLPRQKVKQMFKEADTdANQGTLDFEEFCAFYKMMSTRRDLYLLMLTYS 248
Cdd:cd16219      1 WIRDWFQKADKNKDGRMNFKEVRDLLKMMNVDMNEEHALRLFQMADK-SESGTLEGEEFVLFYKALTQREDVLKIFQDFS 79

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  249 NHKDYLDTDDLKRFLETEQKMTNVTKEHCLEIISKFEPCPENKKEGALGIDGFTNYMRSP 308
Cdd:cd16219     80 ADGQKLTLLEFVDFLQQEQLERENTEELAMELIDRYEPSDTAKKLHALSIDGFLMYLCSP 139
PLN02223 PLN02223
phosphoinositide phospholipase C
 301-874 3.58e-27

phosphoinositide phospholipase C


Pssm-ID: 165867 [Multi-domain]  Cd Length: 537  Bit Score: 118.59  E-value: 3.58e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  301 FTNYMRSPSGDifnpehyQV-NQDMSYPLSHYFITSSHNTYLMGDQLMSQS-RVDMYAWVLQSGCRCVEVDCWdgPDGEP 378
Cdd:PLN02223    91 FSTELNPPIGD-------QVrHHDMHAPLSHYFIHTSLKSYFTGNNVFGKLySIEPIIDALEQGVRVVELDLL--PDGKD 161

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  379 --IVHHGYTLTSKILFKDVIETINKYAFIK-NEYPVILSIENHCSIVQQKKMAQYLTEILGDKLdlssVHSDDSTKL--- 452
Cdd:PLN02223   162 giCVRPKWNFEKPLELQECLDAIKEHAFTKcRSYPLIITFKDGLKPDLQSKATQMIDQTFGDMV----YHEDPQHSLeef 237

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  453 PSPASLKGKILVKgKKLPAnisddaeegevsdedsadeidddcKLMNGDASANRKRVENiakkkldslikESKIRD-CED 531
Cdd:PLN02223   238 PSPAELQNKILIS-RRPPK------------------------ELLYAKADDGGVGVRN-----------ELEIQEgPAD 281

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  532 PNnftvstlpspgkaglksdskkskleddvetgedfsaskrhsrslmgsfskrkkkgsklkkassleegeddsdsqgnla 611
Cdd:PLN02223   282 KN------------------------------------------------------------------------------ 283

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  612 rssvhysrvnrqkktmklsralsdlvkYTKSVGIHDVETElsssWQVSSFSETKAHQIlqQKPAQYLR----FNQHQLSR 687
Cdd:PLN02223   284 ---------------------------YQSLVGFHAVEPR----GMLQKALTGKADDI--QQPGWYERdiisFTQKKFLR 330

                          410       420       430       440       450       460       470       480
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  688 IYPSSYRVDS-SNYNPQPFWNAGCQLVALNYQSEGRMLQLNRAKFSANGNCGYVLKPNCMCQ----GVFNPnSEDPLpgq 762
Cdd:PLN02223   331 TRPKKKNLLInAPYKPQRAWMHGAQLIALSRKDDKEKLWLMQGMFRANGGCGYVKKPDFLLNagpsGVFYP-TENPV--- 406

                          490       500       510       520       530       540       550       560
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  763 LKKQLVLRIISGQ-----------QLPKPrdsmlgdrgeiiDPFVEVEVIGLPVDcFKEQTRVVDDNGFNPMWEETLVFT 831
Cdd:PLN02223   407 VVKILKVKIYMGDgwivdfkkrigRLSKP------------DLYVRISIAGVPHD-EKIMKTTVKNNEWKPTWGEEFTFP 473

                          570       580       590       600
                   ....*....|....*....|....*....|....*....|....
gi 1799905226  832 VHMPEIALIRFLVWDHDPIGRD-FIGQRTIAFSSMMPGYRHVYL 874
Cdd:PLN02223   474 LTYPDLALISFEVYDYEVSTADaFCGQTCLPVSELIEGIRAVPL 517
EFh_ScPlc1p_like cd16207
EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar ...
 166-308 3.23e-23

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: 97.32  E-value: 3.23e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  166 RDQWlKQTfDEADKNGDGSLSISEVLQLMHKLNVNLPRQKVKQMFKEADTDaNQGTLDFEEFCAFYKMMSTRRDLYLLML 245
Cdd:cd16207      2 RIHW-KRA-DSKKQDGDERLDFEDVEKLCRRLHINCSESYLRELFDKADTD-KKGYLNFEEFQEFVKLLKRRKDIKAIFK 78

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1799905226  246 TY-SNHKDYLDTDDLKRFLETEQKmTNVTKEHCLEIISKFEPCPENKKEGALGIDGFTNYMRSP 308
Cdd:cd16207     79 QLtKPGSDGLTLEEFLKFLRDVQK-EDVDRETWEKIFEKFARRIDDSDSLTMTLEGFTSFLLSS 141
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 766-874 2.01e-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: 93.71  E-value: 2.01e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226   766 QLVLRIISGQQLPKPrdsmlgDRGEIIDPFVEVEVIGLPVDCFKeqTRVVDDNGfNPMWEETLVFTVHMPEIALIRFLVW 845
Cdd:smart00239    1 TLTVKIISARNLPPK------DKGGKSDPYVKVSLDGDPKEKKK--TKVVKNTL-NPVWNETFEFEVPPPELAELEIEVY 71

                            90       100       110
                    ....*....|....*....|....*....|
gi 1799905226   846 DHDPIGRD-FIGQRTIAFSSMMPGYRHVYL 874
Cdd:smart00239   72 DKDRFGRDdFIGQVTIPLSDLLLGGRHEKL 101
C2 pfam00168
C2 domain;
766-871 3.01e-20

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 87.37  E-value: 3.01e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  766 QLVLRIISGQQLPKPrdsmlgDRGEIIDPFVEVEVIGlpvDCFKEQTRVVDdNGFNPMWEETLVFTVHMPEIALIRFLVW 845
Cdd:pfam00168    2 RLTVTVIEAKNLPPK------DGNGTSDPYVKVYLLD---GKQKKKTKVVK-NTLNPVWNETFTFSVPDPENAVLEIEVY 71

                           90       100
                   ....*....|....*....|....*..
gi 1799905226  846 DHDPIGRD-FIGQRTIAFSSMMPGYRH 871
Cdd:pfam00168   72 DYDRFGRDdFIGEVRIPLSELDSGEGL 98
PI-PLCc_GDPD_SF cd08555
Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases ...
 335-440 3.39e-20

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: 89.80  E-value: 3.39e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  335 SSHNTYLMGDQlmsQSRVDMYAWVLQSGCRCVEVDCWDGPDGEPIVHHGYTLT------SKILFKDVIETINKYAFiKNE 408
Cdd:cd08555      2 LSHRGYSQNGQ---ENTLEAFYRALDAGARGLELDVRLTKDGELVVYHGPTLDrttagiLPPTLEEVLELIADYLK-NPD 77

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1799905226  409 YPVILSIENHCSIV----QQKKMAQYLTEILGDKLD 440
Cdd:cd08555     78 YTIILSLEIKQDSPeydeFLAKVLKELRVYFDYDLR 113
EFh_PI-PLCdelta1 cd16217
EF-hand motif found in phosphoinositide phospholipase C delta 1 (PI-PLC-delta1); PI-PLC-delta1, ...
 169-308 5.35e-19

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: 85.18  E-value: 5.35e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  169 WLKQTFDEADKNGDGSLSISEVLQLMHKLNVNLPRQKVKQMFKEADTdANQGTLDFEEFCAFYKMMSTRRDLYLLMLTYS 248
Cdd:cd16217      1 WIHSCLRKADKNKDNKMSFKELKDFLKEINIEVDDDYAEKLFKECDK-SKSGFLEGEEIEEFYKLLTKREEIDVIFGEYA 79

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  249 NHKDYLDTDDLKRFLETEQKmTNVTKEHCLEIISKFEPCPENKKEGALGIDGFTNYMRSP 308
Cdd:cd16217     80 KSDGTMSRNNLLNFLQEEQR-EEVAPAYALSLIEKYEPDETAKAQRQMTKDGFLMYLLSP 138
PH_PLC_plant-like cd13365
Plant-like Phospholipase C (PLC) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) was the ...
 36-151 1.49e-18

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: 83.10  E-value: 1.49e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226   36 TVVERCMSSMQMGTQMIKL--RGGSKglVRFYYLDDHRSCIRWRPSRKNEKAKISIDSIQEVCEGKQSEIFQRYADGSFD 113
Cdd:cd13365      1 RDVIEAITQLKIGSYLLKYgrRGKPH--FRYFWLSPDELTLYWSSPKKGSEKRVRLSSVSRIIPGQRTVVFKRPPPPGLE 78

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1799905226  114 pNCCFSIYYGDHMESLDLVSSSAEEARTWITGLKYLMA 151
Cdd:cd13365     79 -EHSFSIIYADGERSLDLTCKDRQEFDTWFTGLRYLLS 115
PH_PLC_delta cd13363
Phospholipase C-delta (PLC-delta) pleckstrin homology (PH) domain; The PLC-delta (PLCdelta) ...
 45-163 2.38e-18

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


Pssm-ID: 270169  Cd Length: 117  Bit Score: 82.37  E-value: 2.38e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226   45 MQMGTQMIKLRGGSKGLVRFYYLDDHRSCIrWRPSRK---NEKAKISIDSIQEVCEGKQSEIFQRYADgSFDPNCCFSIY 121
Cdd:cd13363      1 LLQGSPLLKVRSRSWKKERFYKLQEDCKTV-WHESKKtrsNSKQTFSIEDIESVREGHQSEGLRKYAE-AFPEDRCFSIV 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1799905226  122 YGDHMESLDLVSSSAEEARTWITGLKYLMAGIsdeDSLSKRQ 163
Cdd:cd13363     79 FKGRRKNLDLIAPSEEEAQRWVRGLEKLIARL---TNMSQRE 117
EF-hand_like pfam09279
Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...
 230-314 3.67e-17

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: 78.06  E-value: 3.67e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  230 FYKMMSTRRDLYLLMLTYSNHKDYLDTDDLKRFLETEQKMTNVTKEHCLEIISKFEPCPENKKEGALGIDGFTNYMRSPS 309
Cdd:pfam09279    1 FYKMLTQREEIDEIFQEYSGDGQKLSLDELVDFLREEQREEDASPALALSLIERYEPSETAKKQHAMTKDGFLMYLCSPD 80


                   ....*
gi 1799905226  310 GDIFN 314
Cdd:pfam09279   81 GSIFN 85
PH_PLC_gamma cd13362
Phospholipase C-gamma (PLC-gamma) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is ...
 45-151 4.29e-17

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: 78.86  E-value: 4.29e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226   45 MQMGTQMIKLRGGSK-----GLVRFyyldDHRSCIRWRPSRKNEKAKISIDSIQEVCEGKQSEIFQRYADGS--FDPNCC 117
Cdd:cd13362      1 LERGTVMTKFYQKKRperrtFQVKL----ETRQVVWSRGGGKRAEGAVDIREIKEIRPGKNSKDFERWPDEAkkLDPSCC 76

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 1799905226  118 FSIYYGDH--MESLDLVSSSAEEARTWITGLKYLMA 151
Cdd:cd13362     77 FVILYGTEfrLKTLSVAATSEEECDMWIKGLRYLVE 112
EFh_PI-PLCzeta cd16204
EF-hand motif found in phosphoinositide phospholipase C zeta 1 (PI-PLC-zeta1); PI-PLC-zeta1, ...
 182-307 5.49e-17

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: 79.47  E-value: 5.49e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  182 DGSLSISEVLQLMHKLNVNLPRQKVKQMFKEADTdANQGTLDFEEFCAFYKMMSTRRDLYLLMLTYSNHKDYLDTDDLKR 261
Cdd:cd16204     16 KGKINLESTLKLLEKLDIPFDYIHVKYIFKKNDS-FKAGNITIEDFRAIYRAIAHRCEIHEIFNTYSENRKILSAPNLVG 94

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1799905226  262 FLETEQKMTNVTKEHCLEIISKFEPCPENKKEGALGIDGFTNYMRS 307
Cdd:cd16204     95 FLKKEQFQDEADETIASELIAKYEPIEEVRKRKQMSFEGFIRYMTS 140
EFh cd00051
EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...
 169-235 1.20e-15

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: 72.97  E-value: 1.20e-15
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1799905226  169 WLKQTFDEADKNGDGSLSISEVLQLMHKLNVNLPRQKVKQMFKEADTDANqGTLDFEEFCafyKMMS 235
Cdd:cd00051      1 ELREAFRLFDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGD-GKIDFEEFL---ELMA 63
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 767-857 2.57e-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: 73.26  E-value: 2.57e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  767 LVLRIISGQQLPKPrdsmlgDRGEIIDPFVEVEVIGLpvdcFKEQTRVVDDNgFNPMWEETLVFTVHMPEIALIRFLVWD 846
Cdd:cd00030      1 LRVTVIEARNLPAK------DLNGKSDPYVKVSLGGK----QKFKTKVVKNT-LNPVWNETFEFPVLDPESDTLTVEVWD 69

                           90
                   ....*....|..
gi 1799905226  847 HDPIGRD-FIGQ 857
Cdd:cd00030     70 KDRFSKDdFLGE 81
EFh_PI-PLCdelta3 cd16218
EF-hand motif found in phosphoinositide phospholipase C delta 3 (PI-PLC-delta3); PI-PLC-delta3, ...
 169-308 8.63e-14

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: 70.16  E-value: 8.63e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  169 WLKQTFDEADKNGDGSLSISEVLQLMHKLNVNLPRQKVKQMFKEADTdANQGTLDFEEFCAFYKMMSTRRDLYLLMLTYS 248
Cdd:cd16218      1 WIHEYLRRADLNKDGKMSFEEIKDLLQMINIDLNEQYAYQLFKECDR-SNDDRLEEHEIEEFCRRLMQRPELEEIFHQYS 79

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  249 NHKDYLDTDDLKRFLEtEQKmTNVTKEHCLEIISKFEPCPENKKEGALGIDGFTNYMRSP 308
Cdd:cd16218     80 GEDCVLSAEELREFLK-DQG-EDASLVHAKELIQTYELNEKAKQHQLMTLDGFTMYMLSK 137
EF-hand_7 pfam13499
EF-hand domain pair;
167-232 1.01e-13

EF-hand domain pair;


Pssm-ID: 463900 [Multi-domain]  Cd Length: 67  Bit Score: 67.66  E-value: 1.01e-13
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1799905226  167 DQWLKQTFDEADKNGDGSLSISEVLQLMHKL--NVNLPRQKVKQMFKEADTDANqGTLDFEEFCAFYK 232
Cdd:pfam13499    1 EEKLKEAFKLLDSDGDGYLDVEELKKLLRKLeeGEPLSDEEVEELFKEFDLDKD-GRISFEEFLELYS 67
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
159-230 6.56e-11

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 61.73  E-value: 6.56e-11
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1799905226  159 LSKRQRTRDQWLKQTFDEADKNGDGSLSISEVLQLMHKLNVnlPRQKVKQMFKEADTDANqGTLDFEEFCAF 230
Cdd:COG5126     60 ESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTALGV--SEEEADELFARLDTDGD-GKISFEEFVAA 128
EFh_PI-PLCbeta cd16200
EF-hand motif found in metazoan phosphoinositide-specific phospholipase C (PI-PLC)-beta ...
 188-308 1.53e-10

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: 61.11  E-value: 1.53e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  188 SEVLQLMHKLNvnLPRQKVKQMFKEAdtdanqgtLDFEEFCAFYKMMSTRRDLYLLMLTYS-NHKDYLDTDDLKRFLETE 266
Cdd:cd16200     33 KRVLKALKALG--LPDGKNDEIDPED--------FTFEKFFKLYNKLCPRPDIDEIFKELGgKRKPYLTLEQLVDFLNEE 102

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1799905226  267 Q---KMTNV-----TKEHCLEIISKFEPCPENKKEGALGIDGFTNYMRSP 308
Cdd:cd16200    103 QrdpRLNEIlfpfhTKEQAKKLIDKYEPNEKNKKKGQLTLEGFLRYLMSD 152
PH_12 pfam16457
Pleckstrin homology domain;
37-150 3.34e-10

Pleckstrin homology domain;


Pssm-ID: 465123 [Multi-domain]  Cd Length: 128  Bit Score: 59.58  E-value: 3.34e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226   37 VVERCMSSMQMGTQMIKLRGGSKGL-VRFYYLDDHRSCIRW---------RPSRKNEKAKISIDSIQEVCEGKQSEIFQR 106
Cdd:pfam16457    1 VKEQRLNCLLEGAWFPKVRGRRRKKkYRFCRLSPNRKVLHYgdfeekptvDPSLESLPEKIDLSDIKEVVTGKECPHVRE 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1799905226  107 YADGSF--DPNCCFSIYYGDHM-ESLDLVSSSAEEARTWITGLKYLM 150
Cdd:pfam16457   81 SGKKSKktSSTLAFSLIYGADEyELLDFVAPSESVAAIWLDGLNMLL 127
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
158-239 1.99e-08

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 54.80  E-value: 1.99e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  158 SLSKRQRTRDQWLKQTFDEADKNGDGSLSISEVLQLMHKLNVNLPRQKVKQMFKEADTDANqGTLDFEEFCAFYKMMSTR 237
Cdd:COG5126     23 ERDDFEALFRRLWATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDTDGD-GKISADEFRRLLTALGVS 101


                   ..
gi 1799905226  238 RD 239
Cdd:COG5126    102 EE 103
EH cd00052
Eps15 homology domain; found in proteins implicated in endocytosis, vesicle transport, and ...
 171-228 4.69e-08

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: 51.45  E-value: 4.69e-08
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1799905226  171 KQTFDEADKNGDGSLSISEVLQLMhkLNVNLPRQKVKQMFKEADTDaNQGTLDFEEFC 228
Cdd:cd00052      2 DQIFRSLDPDGDGLISGDEARPFL--GKSGLPRSVLAQIWDLADTD-KDGKLDKEEFA 56
PTZ00184 PTZ00184
calmodulin; Provisional
 171-237 2.63e-07

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 51.69  E-value: 2.63e-07
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1799905226  171 KQTFDEADKNGDGSLSISEVLQLMHKLNVNLPRQKVKQMFKEADTDANqGTLDFEEFCAfykMMSTR 237
Cdd:PTZ00184    14 KEAFSLFDKDGDGTITTKELGTVMRSLGQNPTEAELQDMINEVDADGN-GTIDFPEFLT---LMARK 76
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 764-860 3.29e-07

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: 50.71  E-value: 3.29e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  764 KKQLVLRIISGQQLPKPRDSMLGDrgeiidPFVEVEVIGLPVDCFKEQTRVVDdNGFNPMWEETLVFTVHMPEIALIRFL 843
Cdd:cd04031     15 TSQLIVTVLQARDLPPRDDGSLRN------PYVKVYLLPDRSEKSKRRTKTVK-KTLNPEWNQTFEYSNVRRETLKERTL 87

                           90       100
                   ....*....|....*....|.
gi 1799905226  844 ---VWDHDPIG-RDFIGQRTI 860
Cdd:cd04031     88 evtVWDYDRDGeNDFLGEVVI 108
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 766-853 4.43e-07

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: 50.27  E-value: 4.43e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  766 QLVLRIISGQQLPkprdsmlgdrGEIIDPFVEVEVIGLpvdcfKEQTRVVDDNGfNPMWEETLVFTVHMP--EI--ALIR 841
Cdd:cd04011      5 QVRVRVIEARQLV----------GGNIDPVVKVEVGGQ-----KKYTSVKKGTN-CPFYNEYFFFNFHESpdELfdKIIK 68

                           90
                   ....*....|..
gi 1799905226  842 FLVWDHDPIGRD 853
Cdd:cd04011     69 ISVYDSRSLRSD 80
EFh_PI-PLCbeta4 cd16211
EF-hand motif found in phosphoinositide phospholipase C beta 4 (PI-PLC-beta4); PI-PLC-beta4, ...
 224-307 5.45e-07

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: 50.88  E-value: 5.45e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  224 FEEFCAFYKMMSTRRDLYLLMLTYS-NHKDYLDTDDLKRFLETEQKMTNVT--------KEHCLEIISKFEPCPENKKEG 294
Cdd:cd16211     59 FEKFYELYHKICPRTDIEELFKKINgDKKDYLTVDQLISFLNEHQRDPRLNeilfpfydRKRVMQIIETYEVDEEFKKKE 138

                           90
                   ....*....|...
gi 1799905226  295 ALGIDGFTNYMRS 307
Cdd:cd16211    139 QLSSDGFCRYLMS 151
PI-PLCc_bacteria_like cd08557
Catalytic domain of bacterial phosphatidylinositol-specific phospholipase C and similar ...
 327-464 6.22e-07

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: 52.87  E-value: 6.22e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  327 PLSHYFITSSHNTYlmgDQLMSQSRVDMYAWV----------LQSGCRCVEVDCW-DGPDGEPIVHHGYTLTSKILFKDV 395
Cdd:cd08557      8 PLSQLSIPGTHNSY---AYTIDGNSPIVSKWSktqdlsitdqLDAGVRYLDLRVAyDPDDGDLYVCHGLFLLNGQTLEDV 84

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1799905226  396 IETINkyAFIK---NEyPVILSIENHCSI---VQQKKMAQYLTEILGDKLDLSSVHSDDSTKLpspASL-KGKILV 464
Cdd:cd08557     85 LNEVK--DFLDahpSE-VVILDLEHEYGGdngEDHDELDALLRDVLGDPLYRPPVRAGGWPTL---GELrAGKRVL 154
PTZ00184 PTZ00184
calmodulin; Provisional
 170-237 2.60e-06

calmodulin; Provisional


Pssm-ID: 185504 [Multi-domain]  Cd Length: 149  Bit Score: 48.99  E-value: 2.60e-06
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1799905226  170 LKQTFDEADKNGDGSLSISEVLQLMHKLNVNLPRQKVKQMFKEADTDANqGTLDFEEFCafyKMMSTR 237
Cdd:PTZ00184    86 IKEAFKVFDRDGNGFISAAELRHVMTNLGEKLTDEEVDEMIREADVDGD-GQINYEEFV---KMMMSK 149
EFh_PI-PLCgamma cd16201
EF-hand motif found in phosphoinositide phospholipase C gamma isozymes (PI-PLC-gamma); ...
 169-268 2.89e-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: 48.72  E-value: 2.89e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  169 WLKQTFDEADKNGDGSLSISEVLQLMHKLNVNLPRQKVKQMFKEADTDaNQGTLDFEEFCAFYKmmstrrdlyllMLTYS 248
Cdd:cd16201      1 WLRKEFYSMDRTRRETVTLKDLKAFLPRVNCKISTNKLREKFQEVDTR-RRGELGFDDFAQLYH-----------KLMFD 68

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1799905226  249 NH------KDYLDTDD--------LKRFLETEQK 268
Cdd:cd16201     69 QKiiedffKKYSYSSDgqtvtledFQRFLLEEQK 102
EFh_PI-PLC21 cd16213
EF-hand motif found in phosphoinositide phospholipase PLC21 and similar proteins; The family ...
 222-307 4.28e-06

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: 48.45  E-value: 4.28e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  222 LDFEEFCAFYKMMSTRRDLYLLMLTYSN-HKDYLDTDDLKRFLETEQKMTNV--------TKEHCLEIISKFEPCPENKK 292
Cdd:cd16213     58 FTFEDFFNFYRRLTGRQEVEKIFDELGAkKKPYLTTEQFVDFLNKTQRDPRLneilypyaNPKRARDLINQYEPNKSFAK 137

                           90
                   ....*....|....*
gi 1799905226  293 EGALGIDGFTNYMRS 307
Cdd:cd16213    138 KGHLSVEGFLRYLMS 152
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 751-871 5.47e-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: 5.47e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  751 FNPNSEdplpgqlkkQLVLRIISGQQLPKPrdsmlgDRGEIIDPFVEVEVIGLPVDCFKEQTRVVDDNgFNPMWEETLVF 830
Cdd:cd00276      9 YLPTAE---------RLTVVVLKARNLPPS------DGKGLSDPYVKVSLLQGGKKLKKKKTSVKKGT-LNPVFNEAFSF 72

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1799905226  831 TV---HMPEIALIrFLVWDHDPIGRD-FIGQRTIAFSSMMPGYRH 871
Cdd:cd00276     73 DVpaeQLEEVSLV-ITVVDKDSVGRNeVIGQVVLGPDSGGEELEH 116
FRQ1 COG5126
Ca2+-binding protein, EF-hand superfamily [Signal transduction mechanisms];
170-284 8.19e-06

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


Pssm-ID: 444056 [Multi-domain]  Cd Length: 137  Bit Score: 47.09  E-value: 8.19e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  170 LKQTFDEADKNGDGSLSISEVLQLMHKLnvnlprqkVKQMFKEADTDANqGTLDFEEFCAFYKMMSTRRDLYLLMLTYS- 248
Cdd:COG5126      7 LDRRFDLLDADGDGVLERDDFEALFRRL--------WATLFSEADTDGD-GRISREEFVAGMESLFEATVEPFARAAFDl 77

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1799905226  249 ---NHKDYLDTDDLKRFLEteqkMTNVTKEHCLEIISKF 284
Cdd:COG5126     78 ldtDGDGKISADEFRRLLT----ALGVSEEEADELFARL 112
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 793-866 8.84e-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: 8.84e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1799905226  793 DPFVEVEVIGLPVDCFKEQTRVVDDNgFNPMWEETLVFTVHMPEiaLIRFL---VWDHDPIGR-DFIGQRTIAFSSMM 866
Cdd:cd04026     35 DPYVKLKLIPDPKNETKQKTKTIKKT-LNPVWNETFTFDLKPAD--KDRRLsieVWDWDRTTRnDFMGSLSFGVSELI 109
PTZ00183 PTZ00183
centrin; Provisional
 170-227 2.93e-05

centrin; Provisional


Pssm-ID: 185503 [Multi-domain]  Cd Length: 158  Bit Score: 46.22  E-value: 2.93e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1799905226  170 LKQTFDEADKNGDGSLSISEVLQLMHKLNVNLPRQKVKQMFKEADTDANqGTLDFEEF 227
Cdd:PTZ00183    19 IREAFDLFDTDGSGTIDPKELKVAMRSLGFEPKKEEIKQMIADVDKDGS-GKIDFEEF 75
EFh_NorpA_like cd16212
EF-hand motif found in Drosophila melanogaster No receptor potential A protein (NorpA) and ...
 198-307 2.94e-05

EF-hand motif found in Drosophila melanogaster No receptor potential A protein (NorpA) and similar proteins; NorpA, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase, is an eye-specific phosphoinositide phospholipase C (PI-PLC) encoded by norpA gene in Drosophila. It is expressed predominantly in photoreceptors and plays an essential role in the phototransduction pathway of Drosophila. A mutation within the norpA gene can render the fly blind without affecting any of the obvious structures of the eye. Like beta-class of vertebrate PI-PLCs, NorpA 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: 320042 [Multi-domain]  Cd Length: 153  Bit Score: 46.00  E-value: 2.94e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  198 NVNLPRQKVKQMFKEADTdanqgtldFEEFCAFYKMMSTRRDLYLLMLTYSNHK-DYLDTDDLKRFLETEQK---MTNV- 272
Cdd:cd16212     41 EMGLPSGKGDSIEKEDFT--------FEKFYALYHKICPRNDIEELFTSITKGKgEHISLAQLINFMNDKQRdprLNEIl 112

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1799905226  273 ----TKEHCLEIISKFEPCPENKKEGALGIDGFTNYMRS 307
Cdd:cd16212    113 yplyDEKRCTEIIKAYEQNEENIKNKRMSKDGFIRYLMS 151
C2_putative_Elicitor-responsive_gene cd04049
C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive ...
 792-860 4.99e-05

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: 44.63  E-value: 4.99e-05
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1799905226  792 IDPFVEVEviglpvdcFKEQTR---VVDDNGFNPMWEETLVFTVHMPEIAL---IRFLVWDHDPI-GRDFIGQRTI 860
Cdd:cd04049     22 IDPYVIIQ--------CRTQERkskVAKGDGRNPEWNEKFKFTVEYPGWGGdtkLILRIMDKDNFsDDDFIGEATI 89
EF-hand_10 pfam14788
EF hand;
185-234 6.21e-05

EF hand;


Pssm-ID: 405477  Cd Length: 50  Bit Score: 42.02  E-value: 6.21e-05
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1799905226  185 LSISEVLQLMHKLNVNLPRQKVKQMFKEADTDANqGTLDFEEFCAFYKMM 234
Cdd:pfam14788    2 MSFKELKNFLRLINIEVDDSYARKLFQKCDTSQS-GRLEGEEIEEFYKLL 50
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 767-871 8.77e-05

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: 43.86  E-value: 8.77e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  767 LVLRIISGQQLPKPrdsmlgDRGEIIDPFVEVEVigLPVDCFKEQTRVVDDNgFNPMWEETLVFTVHMPEIALIRFL--- 843
Cdd:cd08386     18 LTLKILKAVELPAK------DFSGTSDPFVKIYL--LPDKKHKLETKVKRKN-LNPHWNETFLFEGFPYEKLQQRVLylq 88

                           90       100       110
                   ....*....|....*....|....*....|....
gi 1799905226  844 VWDH------DPIGRDFIGQRTIAFSSMMPGYRH 871
Cdd:cd08386     89 VLDYdrfsrnDPIGEVSLPLNKVDLTEEQTFWKD 122
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
 170-236 1.04e-04

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


Pssm-ID: 320060 [Multi-domain]  Cd Length: 163  Bit Score: 44.51  E-value: 1.04e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1799905226  170 LKQTFDEADKNGDGSLSISEVLQLMHKLNVNLPRQKVKQMFKEADTDANqGTLDFEEFCAFYKMMST 236
Cdd:cd16185      2 LRQWFRAVDRDRSGSIDVNELQKALAGGGLLFSLATAEKLIRMFDRDGN-GTIDFEEFAALHQFLSN 67
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 766-871 1.66e-04

C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175976 [Multi-domain]  Cd Length: 133  Bit Score: 43.38  E-value: 1.66e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  766 QLVLRIISGQQLpKPRDSmlgdRGeIIDPFVEVEVigLP----VDCFKEQTRVVDDNgFNPMWEETLVFTV----HMPEI 837
Cdd:cd04009     17 SLRVEILNARNL-LPLDS----NG-SSDPFVKVEL--LPrhlfPDVPTPKTQVKKKT-LFPLFDESFEFNVppeqCSVEG 87

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1799905226  838 ALIRFLVWDHDPIGR-DFIGQRTIAFSSmMPGYRH 871
Cdd:cd04009     88 ALLLFTVKDYDLLGSnDFEGEAFLPLND-IPGVED 121
PRK07764 PRK07764
DNA polymerase III subunits gamma and tau; Validated
 957-1111 1.73e-04

DNA polymerase III subunits gamma and tau; Validated


Pssm-ID: 236090 [Multi-domain]  Cd Length: 824  Bit Score: 46.52  E-value: 1.73e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  957 DTKDSSSAGAGEEQEVEAASQPRFVQEPESASPAPAPRDGAGGEAPGKGlkGKAQGSPKGPRQSCAHP---GAPFSEPLP 1033
Cdd:PRK07764   626 APAPAGAAAAPAEASAAPAPGVAAPEHHPKHVAVPDASDGGDGWPAKAG--GAAPAAPPPAPAPAAPAapaGAAPAQPAP 703

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1799905226 1034 RAHKVRLQEPQGEKQSVFARCAINSSGRIGVATNCMKCMIGSKESPDPEGPWSDHPGRPIARDPLHPEQGSSAEERVE 1111
Cdd:PRK07764   704 APAATPPAGQADDPAAQPPQAAQGASAPSPAADDPVPLPPEPDDPPDPAGAPAQPPPPPAPAPAAAPAAAPPPSPPSE 781
EFh_PEF_ALG-2_like cd16185
EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...
 170-238 1.78e-04

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


Pssm-ID: 320060 [Multi-domain]  Cd Length: 163  Bit Score: 43.74  E-value: 1.78e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1799905226  170 LKQTFDEADKNGDGSLSISEVLQLMHKLNVNLPRQKVKQMFKEADTDaNQGTLDFEEF---CAFykMMSTRR 238
Cdd:cd16185     68 MQNGFEQRDTSRSGRLDANEVHEALAASGFQLDPPAFQALFRKFDPD-RGGSLGFDDYielCIF--LASARN 136
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 205-234 1.85e-04

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


Pssm-ID: 197492 [Multi-domain]  Cd Length: 29  Bit Score: 40.05  E-value: 1.85e-04
                            10        20        30
                    ....*....|....*....|....*....|
gi 1799905226   205 KVKQMFKEADTDANqGTLDFEEFCAFYKMM 234
Cdd:smart00054    1 ELKEAFRLFDKDGD-GKIDFEEFKDLLKAL 29
C2C_Ferlin cd04018
C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 769-890 2.24e-04

C2 domain third repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175985 [Multi-domain]  Cd Length: 151  Bit Score: 43.39  E-value: 2.24e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  769 LRIISGQQLPKPRDSML--------GDRGEIIDPFVEVEVIGLpvdcfKEQTRVVDDNgFNPMWEETLVFTVHMPEIA-L 839
Cdd:cd04018      4 FKIYRAEDLPQMDSGIManvkkaflGEKKELVDPYVEVSFAGQ-----KVKTSVKKNS-YNPEWNEQIVFPEMFPPLCeR 77

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1799905226  840 IRFLVWDHDPIGRD------FIGQRTIAFSS-------MMPGYRHVYLEGIEEASIFVHVAIND 890
Cdd:cd04018     78 IKIQIRDWDRVGNDdvigthFIDLSKISNSGdegflptFGPSFVNLYGSPREYSLLDDHQDLNE 141
EFh_PEF_Group_I cd16180
Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...
 170-232 2.72e-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: 43.29  E-value: 2.72e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1799905226  170 LKQTFDEADKNGDGSLSISEvLQLMHKLNVNLPR--QKVKQMFKEADTDANqGTLDFEEFCAFYK 232
Cdd:cd16180      2 LRRIFQAVDRDRSGRISAKE-LQRALSNGDWTPFsiETVRLMINMFDRDRS-GTINFDEFVGLWK 64
EH smart00027
Eps15 homology domain; Pair of EF hand motifs that recognise proteins containing Asn-Pro-Phe ...
 172-229 3.11e-04

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


Pssm-ID: 197477 [Multi-domain]  Cd Length: 96  Bit Score: 41.49  E-value: 3.11e-04
                            10        20        30        40        50
                    ....*....|....*....|....*....|....*....|....*....|....*...
gi 1799905226   172 QTFDEADKNGDGSLSISEVLQLMhkLNVNLPRQKVKQMFKEADTDANqGTLDFEEFCA 229
Cdd:smart00027   14 QIFRSLDKNQDGTVTGAQAKPIL--LKSGLPQTLLAKIWNLADIDND-GELDKDEFAL 68
EFh_PI-PLCepsilon cd16203
EF-hand motif found in phosphoinositide phospholipase C epsilon 1 (PI-PLC-epsilon1); ...
 258-305 3.49e-04

EF-hand motif found in phosphoinositide phospholipase C epsilon 1 (PI-PLC-epsilon1); PI-PLC-epsilon1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase epsilon-1, or pancreas-enriched phospholipase C, or phospholipase C-epsilon-1 (PLC-epsilon-1), is dominant in connective tissues and brain. It has been implicated in carcinogenesis, such as in bladder and intestinal tumor, oesophageal squamous cell carcinoma, gastric adenocarcinoma, murine skin cancer, head and neck cancer. PI-PLC-epsilon1 contains an N-terminal CDC25 homology domain with a guanyl-nucleotide exchange factor (GFF) activity, a pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core domain, a C2 domain, and at least one and perhaps two C-terminal predicted RA (Ras association) domains that are implicated in the binding of small GTPases, such as Ras or Rap, from the Ras family. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. There is only one PI-PLC-epsilon isozyme. It is directly activated by G alpha(12/13), G beta gamma, and activated members of Ras and Rho small GTPases.


Pssm-ID: 320033  Cd Length: 174  Bit Score: 43.47  E-value: 3.49e-04
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1799905226  258 DLKRFLETEQkMTNVTKEHCLEIISKFEPCPENKKEGALGIDGFTNYM 305
Cdd:cd16203    124 QLKDFLENHQ-MEHITEEEAIKIIQRHEPDPILRSKNCLSFEGFARYL 170
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
 205-234 3.54e-04

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


Pssm-ID: 425435 [Multi-domain]  Cd Length: 29  Bit Score: 39.31  E-value: 3.54e-04
                           10        20        30
                   ....*....|....*....|....*....|
gi 1799905226  205 KVKQMFKEADTDANqGTLDFEEFCAFYKMM 234
Cdd:pfam00036    1 ELKEIFRLFDKDGD-GKIDFEEFKELLKKL 29
PRK07764 PRK07764
DNA polymerase III subunits gamma and tau; Validated
 960-1138 4.54e-04

DNA polymerase III subunits gamma and tau; Validated


Pssm-ID: 236090 [Multi-domain]  Cd Length: 824  Bit Score: 45.36  E-value: 4.54e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  960 DSSSAGAGEEQEVEAASQPRFVQEP-----ESASPAPAPRDGAGGEAPGKGLKGKAQGSPKGPRQSCAHPGAPfSEPLPR 1034
Cdd:PRK07764   591 APGAAGGEGPPAPASSGPPEEAARPaapaaPAAPAAPAPAGAAAAPAEASAAPAPGVAAPEHHPKHVAVPDAS-DGGDGW 669

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226 1035 AHKVRLQEPQGEKQSVfARCAinSSGRIGVATNcmkcmigskeSPDPEGPWSDHPGRPIARDPLHPEQGSSAEERVELRT 1114
Cdd:PRK07764   670 PAKAGGAAPAAPPPAP-APAA--PAAPAGAAPA----------QPAPAPAATPPAGQADDPAAQPPQAAQGASAPSPAAD 736

                          170       180
                   ....*....|....*....|....
gi 1799905226 1115 WVVRGQPRPHSDLQPCSSPGTADD 1138
Cdd:PRK07764   737 DPVPLPPEPDDPPDPAGAPAQPPP 760
C2_Munc13_fungal cd04043
C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are ...
 769-853 4.92e-04

C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176008 [Multi-domain]  Cd Length: 126  Bit Score: 41.86  E-value: 4.92e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  769 LRIISGQQLPKPRDSmlgdrgEIIDPFVEVEVIGLPVDCFKeqTRVVDDNgFNPMWEETLVFTVHMPEIALIRFLVWDHD 848
Cdd:cd04043      5 IRIVRAENLKADSSN------GLSDPYVTLVDTNGKRRIAK--TRTIYDT-LNPRWDEEFELEVPAGEPLWISATVWDRS 75


                   ....*
gi 1799905226  849 PIGRD 853
Cdd:cd04043     76 FVGKH 80
C2_E3_ubiquitin_ligase cd04021
C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation ...
 764-865 7.16e-04

C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation mechanism responsible for controlling surface expression of membrane proteins. The sequential action of several enzymes are involved: ubiquitin-activating enzyme E1, ubiquitin-conjugating enzyme E2, and ubiquitin-protein ligase E3 which is responsible for substrate recognition and promoting the transfer of ubiquitin to the target protein. E3 ubiquitin ligase is composed of an N-terminal C2 domain, 4 WW domains, and a HECTc 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.


Pssm-ID: 175988 [Multi-domain]  Cd Length: 125  Bit Score: 41.49  E-value: 7.16e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  764 KKQLVLRIISGqqlpKPRDSMLGDRGeiiDPFVEVEVIGLPVdcfkEQTRVVDdNGFNPMWEETlvFTVHMPEIALIRFL 843
Cdd:cd04021      1 KSQLQITVESA----KLKSNSKSFKP---DPYVEVTVDGQPP----KKTEVSK-KTSNPKWNEH--FTVLVTPQSTLEFK 66

                           90       100
                   ....*....|....*....|...
gi 1799905226  844 VWDHDPIGRD-FIGQRTIAFSSM 865
Cdd:cd04021     67 VWSHHTLKADvLLGEASLDLSDI 89
EF-hand_1 pfam00036
EF hand; The EF-hands can be divided into two classes: signalling proteins and buffering ...
 170-197 7.48e-04

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


Pssm-ID: 425435 [Multi-domain]  Cd Length: 29  Bit Score: 38.54  E-value: 7.48e-04
                           10        20
                   ....*....|....*....|....*...
gi 1799905226  170 LKQTFDEADKNGDGSLSISEVLQLMHKL 197
Cdd:pfam00036    2 LKEIFRLFDKDGDGKIDFEEFKELLKKL 29
EFh_CREC cd15899
EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin ...
 171-226 9.83e-04

EF-hand, calcium binding motif, found in CREC-EF hand family; The CREC (Cab45/reticulocalbin/ERC45/calumenin)-EF hand family contains a group of six EF-hand, low-affinity Ca2+-binding proteins, including reticulocalbin (RCN-1), ER Ca2+-binding protein of 55 kDa (ERC-55, also known as TCBP-49 or E6BP), reticulocalbin-3 (RCN-3), Ca2+-binding protein of 45 kDa (Cab45 and its splice variant Cab45b), and calumenin ( also known as crocalbin or CBP-50). The proteins are not only localized in various parts of the secretory pathway, but also found in the cytosolic compartment and at the cell surface. They interact with different ligands or proteins and have been implicated in the secretory process, chaperone activity, signal transduction as well as in a large variety of disease processes.


Pssm-ID: 320021 [Multi-domain]  Cd Length: 267  Bit Score: 43.20  E-value: 9.83e-04
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1799905226  171 KQTFDE-ADKNGDGSLSISEVLQLMHKLNVNLPRQKVKQMFKEADTDANqGTLDFEE 226
Cdd:cd15899    203 KERFVElRDKDKDGKLDGEELLSWVDPSNQEIALEEAKHLIAESDENKD-GKLSPEE 258
C2A_Copine cd04048
C2 domain first repeat in Copine; There are 2 copies of the C2 domain present in copine, a ...
 771-874 1.34e-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: 40.25  E-value: 1.34e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  771 IISGQQLPKPrdsmlgDRGEIIDPFVEVEVIGLPVDCFKE--QTRVVDDNgFNPMWEETLVFTVHMPEIALIRFLVWDHD 848
Cdd:cd04048      6 SISCRNLLDK------DVLSKSDPFVVVYVKTGGSGQWVEigRTEVIKNN-LNPDFVTTFTVDYYFEEVQKLRFEVYDVD 78

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1799905226  849 PIGR-----DFIGQRTIAFSSMM--PGYRHVYL 874
Cdd:cd04048     79 SKSKdlsdhDFLGEAECTLGEIVssPGQKLTLP 111
S-100 cd00213
S-100: S-100 domain, which represents the largest family within the superfamily of proteins ...
 177-230 1.81e-03

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


Pssm-ID: 238131 [Multi-domain]  Cd Length: 88  Bit Score: 39.01  E-value: 1.81e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  177 ADKNGD-GSLSISEVLQLMHK-LNVNLPRQK----VKQMFKEADTDANqGTLDFEEFCAF 230
Cdd:cd00213     18 SGKEGDkDTLSKKELKELLETeLPNFLKNQKdpeaVDKIMKDLDVNKD-GKVDFQEFLVL 76
C2A_fungal cd04041
C2 domain first repeat; fungal group; C2 domains were first identified in Protein Kinase C ...
 786-849 2.16e-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: 2.16e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  786 GDRGEI-IDPFVEV--EVIGLPVDCfkeqTRVVDDNgFNPMWEETLVFTVHMPEIAL---IRFLVWDHDP 849
Cdd:cd04041     16 ADFGTGsSDPYVTAsfAKFGKPLYS----TRIIRKD-LNPVWEETWFVLVTPDEVKAgerLSCRLWDSDR 80
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 767-886 2.29e-03

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: 40.01  E-value: 2.29e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  767 LVLRIISGQQLPkPRDSMLGdrgeiIDPFVEVEViglpvDCFKEQTRVVDDNgFNPMWEETLVFTVHMPEIALIRFL--- 843
Cdd:cd04022      2 LVVEVVDAQDLM-PKDGQGS-----SSAYVELDF-----DGQKKRTRTKPKD-LNPVWNEKLVFNVSDPSRLSNLVLevy 69

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1799905226  844 VWDH--DPIGRDFIGQRTIAFSSMMP----GYRHVYLegiEEASIFVHV 886
Cdd:cd04022     70 VYNDrrSGRRRSFLGRVRISGTSFVPpseaVVQRYPL---EKRGLFSRV 115
C2_plant_PLD cd04015
C2 domain present in plant phospholipase D (PLD); PLD hydrolyzes terminal phosphodiester bonds ...
 769-860 2.68e-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: 40.37  E-value: 2.68e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  769 LRIISGQQLPKPRDSMLGDRGEII--DPFVEVEVIGLPVdcfkEQTRVVDDNGfNPMWEET-LVFTVHMpeIALIRFLVW 845
Cdd:cd04015     33 FSKLVGCSEPTLKRPSSHRHVGKItsDPYATVDLAGARV----ARTRVIENSE-NPVWNESfHIYCAHY--ASHVEFTVK 105

                           90
                   ....*....|....*
gi 1799905226  846 DHDPIGRDFIGQRTI 860
Cdd:cd04015    106 DNDVVGAQLIGRAYI 120
EFh smart00054
EF-hand, calcium binding motif; EF-hands are calcium-binding motifs that occur at least in ...
 170-197 2.75e-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: 36.97  E-value: 2.75e-03
                            10        20
                    ....*....|....*....|....*...
gi 1799905226   170 LKQTFDEADKNGDGSLSISEVLQLMHKL 197
Cdd:smart00054    2 LKEAFRLFDKDGDGKIDFEEFKDLLKAL 29
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 762-867 2.82e-03

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176000 [Multi-domain]  Cd Length: 123  Bit Score: 39.57  E-value: 2.82e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  762 QLKKQLVLRIISGQQLpKPRDSmlgdrGEIIDPFVEVEVIGLPVDCFKEQTRVVDdNGFNPMWEETLVFTVHMPEIA--- 838
Cdd:cd04035     12 PANSALHCTIIRAKGL-KAMDA-----NGLSDPYVKLNLLPGASKATKLRTKTVH-KTRNPEFNETLTYYGITEEDIqrk 84

                           90       100
                   ....*....|....*....|....*....
gi 1799905226  839 LIRFLVWDHDPIGRDFIGQRTIAFSSMMP 867
Cdd:cd04035     85 TLRLLVLDEDRFGNDFLGETRIPLKKLKP 113
EF-hand_5 pfam13202
EF hand;
170-194 4.16e-03

EF hand;


Pssm-ID: 433035 [Multi-domain]  Cd Length: 25  Bit Score: 36.14  E-value: 4.16e-03
                           10        20
                   ....*....|....*....|....*
gi 1799905226  170 LKQTFDEADKNGDGSLSISEVLQLM 194
Cdd:pfam13202    1 LKDTFRQIDLNGDGKISKEELRRLL 25
EF-hand_4 pfam12763
Cytoskeletal-regulatory complex EF hand; This is an efhand family from the N-terminal of actin ...
 179-228 4.57e-03

Cytoskeletal-regulatory complex EF hand; This is an efhand family from the N-terminal of actin cytoskeleton-regulatory complex END3 and similar proteins from fungi and closely related species.


Pssm-ID: 289529  Cd Length: 104  Bit Score: 38.51  E-value: 4.57e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|
gi 1799905226  179 KNGDGSLSISEVLQLMHklNVNLPRQKVKQMFKEADTDaNQGTLDFEEFC 228
Cdd:pfam12763   20 KPENNKLTGDQVSPVLK--NSRLPDDQLAKIWDLADID-SDGKLDFEEFC 66
EF-hand_6 pfam13405
EF-hand domain;
169-198 5.05e-03

EF-hand domain;


Pssm-ID: 463869 [Multi-domain]  Cd Length: 30  Bit Score: 36.00  E-value: 5.05e-03
                           10        20        30
                   ....*....|....*....|....*....|
gi 1799905226  169 WLKQTFDEADKNGDGSLSISEVLQLMHKLN 198
Cdd:pfam13405    1 ELREAFKLFDKDGDGKISLEELRKALRSLG 30
EFh_HEF_CBN cd16179
EF-hand, calcium binding motif, found in Drosophila melanogaster calbindin-32 (CBN) and ...
 178-265 5.78e-03

EF-hand, calcium binding motif, found in Drosophila melanogaster calbindin-32 (CBN) and similar proteins; CBN, the product of the cbn gene, is a Drosophila homolog to vertebrate neuronal six EF-hand calcium binding proteins. It is expressed through most of ontogenesis with a selective distribution in the nervous system and in a few small adult thoracic muscles. Its precise biological role remains unclear. CBN contains six EF-hand motifs, but some of them may not bind calcium ions due to the lack of key residues.


Pssm-ID: 320079 [Multi-domain]  Cd Length: 261  Bit Score: 40.47  E-value: 5.78e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  178 DKNGDGSLSISEVLQLM-----------HKLNVNLPRQKVKQMFKEADTDANqGTLDFEEFCAFYKmmstrrDLYLLmlt 246
Cdd:cd16179    151 DRNKDGKLQLSEMARLLpvkenflcrpiFKGAGKLTREDIDRVFALYDRDNN-GTIENEELTGFLK------DLLEL--- 220

                           90
                   ....*....|....*....
gi 1799905226  247 ysNHKDYlDTDDLKRFLET 265
Cdd:cd16179    221 --VQEDY-DEQDLEEFKEI 236
PH smart00233
Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...
 47-151 5.89e-03

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The domain family possesses multiple functions including the abilities to bind inositol phosphates, and various proteins. PH domains have been found to possess inserted domains (such as in PLC gamma, syntrophins) and to be inserted within other domains. Mutations in Brutons tyrosine kinase (Btk) within its PH domain cause X-linked agammaglobulinaemia (XLA) in patients. Point mutations cluster into the positively charged end of the molecule around the predicted binding site for phosphatidylinositol lipids.


Pssm-ID: 214574 [Multi-domain]  Cd Length: 102  Bit Score: 38.30  E-value: 5.89e-03
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226    47 MGTQMIKLRGGSKGLVRFY-YLDDHRSCI---RWRPSRKNEKAKISIDSIQeVCEGKQSEifqryadgSFDPNCCFSIYY 122
Cdd:smart00233    4 EGWLYKKSGGGKKSWKKRYfVLFNSTLLYyksKKDKKSYKPKGSIDLSGCT-VREAPDPD--------SSKKPHCFEIKT 74

                            90       100
                    ....*....|....*....|....*....
gi 1799905226   123 GDHmESLDLVSSSAEEARTWITGLKYLMA 151
Cdd:smart00233   75 SDR-KTLLLQAESEEEREKWVEALRKAIA 102
EFh_CREC_RCN2 cd16224
EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2); RCN2, also termed ...
 171-230 6.21e-03

EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2); RCN2, also termed calcium-binding protein ERC-55, or E6-binding protein (E6BP), or TCBP-49, is an endoplasmic reticulum resident low-affinity Ca2+-binding protein that has been implicated in immunity, redox homeostasis, cell cycle regulation and coagulation. It is associated with tumorigenesis, in particular with transformation of cells of the cervix induced by human papillomavirus (HPV), through binding to human papillomavirus (HPV) E6 oncogenic protein. It specifically interacts with vitamin D receptor among nuclear receptors. RCN2 contains an N-terminal signal sequence followed by six copies of the EF-hand Ca2+-binding motif, and a C-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide that is required for retention of RCN2 in the endoplasmic reticulum (ER).


Pssm-ID: 320022 [Multi-domain]  Cd Length: 268  Bit Score: 40.49  E-value: 6.21e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1799905226  171 KQTFDEADKNGDGSLSISEVLQLMHKLNVNLPRQKV----------------KQMFKEADTDANQGtLDFEEFCAF 230
Cdd:cd16224     75 KQQFPEYDKDGDGAVTWDEYNMQMYDRVIDYDEDTVlddeeeesfrqlhlkdKKRFDKANTDGGPG-LNLTEFIAF 149
EFh_CREC_RCN2_like cd16227
EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This ...
 152-257 6.86e-03

EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This family corresponds to a group of uncharacterized RCN2-like proteins, which are mainly found in protostomes. Although their biological function remains unclear, they show high sequence similarity with RCN2 (also known as E6BP or TCBP-49), which is an endoplasmic reticulum resident low-affinity Ca2+-binding protein that has been implicated in immunity, redox homeostasis, cell cycle regulation and coagulation. Members in this family contain six copies of the EF-hand Ca2+-binding motif, but may lack a C-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide that is required for retention of RCN2 in the endoplasmic reticulum (ER).


Pssm-ID: 320025 [Multi-domain]  Cd Length: 263  Bit Score: 40.38  E-value: 6.86e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  152 GISDED--SLSKRQRTRDQWL----KQTFDEADKNGDGSLSISEVLQL--------MHKLnvnlprqKVKQMFKEADTDa 217
Cdd:cd16227    100 GYDDEDneEMIKDSTEDDLKLleddKEMFEAADLNKDGKLDKTEFSAFqhpeeyphMHPV-------LIEQTLRDKDKD- 171

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1799905226  218 NQGTLDFEEFCAfYKMMSTRRDLYLLMLTysNHKDYLDTD 257
Cdd:cd16227    172 NDGFISFQEFLG-DRAGHEDKEWLLVEKD--RFDEDYDKD 208
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
 781-857 8.49e-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: 38.23  E-value: 8.49e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1799905226  781 RDSMLGDRGEIIDPFVEVEviglpvdcFKEQTR---VVDDNGFnPMWEETLVFTVHMPEIALIRFLVWDHDPIGR-DFIG 856
Cdd:cd04025     10 RDLAPKDRNGTSDPFVRVF--------YNGQTLetsVVKKSCY-PRWNEVFEFELMEGADSPLSVEVWDWDLVSKnDFLG 80


                   .
gi 1799905226  857 Q 857
Cdd:cd04025     81 K 81
EFh_CREC_RCN2_like cd16227
EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This ...
 171-231 9.79e-03

EF-hand, calcium binding motif, found in reticulocalbin-2 (RCN2) mainly from protostomes; This family corresponds to a group of uncharacterized RCN2-like proteins, which are mainly found in protostomes. Although their biological function remains unclear, they show high sequence similarity with RCN2 (also known as E6BP or TCBP-49), which is an endoplasmic reticulum resident low-affinity Ca2+-binding protein that has been implicated in immunity, redox homeostasis, cell cycle regulation and coagulation. Members in this family contain six copies of the EF-hand Ca2+-binding motif, but may lack a C-terminal His-Asp-Glu-Leu (HDEL) tetrapeptide that is required for retention of RCN2 in the endoplasmic reticulum (ER).


Pssm-ID: 320025 [Multi-domain]  Cd Length: 263  Bit Score: 39.99  E-value: 9.79e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1799905226  171 KQTFDEADKNGDGSLSISEVLQ----------LMHKLNVNLPRQKV----KQMFKEADTDaNQGTLDFEEFCAFY 231
Cdd:cd16227     75 NERFEEADEDGDGKVTWEEYLAdsfgyddednEEMIKDSTEDDLKLleddKEMFEAADLN-KDGKLDKTEFSAFQ 148
 
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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