NCBI Conserved Domain Search

Conserved domains on [gi|167900458|ref|NP_001108135|]

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inactive phospholipase C-like protein 1 [Mus musculus]

Protein Classification

PLC family C2 domain-containing protein( domain architecture ID 11598664)

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_PRIP_metazoa

cd08597

Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This ...

399-689

1.41e-166

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: 490.78 E-value: 1.41e-166

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  399 QDMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGPDNEPILCNRNNMAMHLSFRSVLEVINK 478
Cdd:cd08597     2 QDMTQPLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDGPNGEPVIYHGHTLTSKISFRSVIEAINE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  479 FAFVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYTEAPLSSESYLPSPEKLKNMIIVKGKKLpsesdllegevtd 558
Cdd:cd08597    82 YAFVASEYPLILCIENHCSEKQQLVMAQYLKEIFGDKLYTEPPNEGESYLPSPHDLKGKIIIKGKKL------------- 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  559 edeeaemsrrmsgdyngeqKHIWLCRELSDLVSICKSVQHRDFELSMKTQNYWEMCSFSETEASRIANEYPEDFVNYNKK 638
Cdd:cd08597   149 -------------------KRRKLCKELSDLVSLCKSVRFQDFPTSAQNQKYWEVCSFSENLARRLANEFPEDFVNYNKK 209

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 167900458  639 FLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQN 689
Cdd:cd08597   210 FLSRVYPSPMRVDSSNYNPQDFWNCGCQIVAMNYQTPGLMMDLNTGKFLEN 260

EFh_PI-PLC super family

cl28895

EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...

244-386

3.36e-81

EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) isozymes; PI-PLC isozymes are signaling enzymes that hydrolyze the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, Inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which goes on to phosphorylate other molecules, leading to altered cellular activity. Calcium is required for the catalysis. This family corresponds to the four EF-hand motifs containing PI-PLC isozymes, including PI-PLC-beta (1-4), -gamma (1-2), -delta (1,3,4), -epsilon (1), -zeta (1), eta (1-2). Lower eukaryotes such as yeast and slime molds contain only delta-type isozymes. In contrast, other types of isoforms present in higher eukaryotes. This family also includes 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1 (PLC1) from fungi. Some homologs from plants contain only two atypical EF-hand motifs and they are not included. All PI-PLC isozymes except sperm-specific PI-PLC-zeta share a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. PI-PLC-zeta lacks the PH domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Most of EF-hand motifs found in PI-PLCs consist of a helix-loop-helix structure, but lack residues critical to metal binding. Moreover, the EF-hand region of most of PI-PLCs may have an important regulatory function, but it has yet to be identified. However, PI-PLC-zeta is a key exception. It is responsible for Ca2+ oscillations in fertilized oocytes and exhibits a high sensitivity to Ca2+ mediated through its EF-hand domain. In addition, PI-PLC-eta2 shows a canonical EF-loop directing Ca2+-sensitivity and thus can amplify transient Ca2+ signals. Also it appears that PI-PLC-delta1 can regulate the binding of PH domain to PIP2 in a Ca2+-dependent manner through its functionally important EF-hand domains. PI-PLCs can be activated by a variety of extracellular ligands, such as growth factors, hormones, cytokines and lipids. Their activation has been implicated in tumorigenesis and/or metastasis linked to migration, proliferation, growth, inflammation, angiogenesis and actin cytoskeleton reorganization. PI-PLC-beta isozymes are activated by G-protein coupled receptor (GPCR) through different mechanisms. However, PI-PLC-gamma isozymes are activated by receptor tyrosine kinase (RTK), such as Rho and Ras GTPases. In contrast, PI-PLC-epsilon are activated by both GPCR and RTK. PI-PLC-delta1 and PLC-eta 1 are activated by GPCR-mediated calcium mobilization. The activation mechanism for PI-PLC-zeta remains unclear.

The actual alignment was detected with superfamily member cd16222:

Pssm-ID: 333715 [Multi-domain] Cd Length: 143 Bit Score: 260.95 E-value: 3.36e-81

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  244 WLKTVFEAADVDGNGIMLEDTSVELIKQLNPTLKESKIRLKFKEIQKSKEKLTTRVTEEEFCEAFCELCTRPEVYFLLVQ 323
Cdd:cd16222     1 WLSAVFEAADVDGYGIMLEDTAVELIKQLNPGIKEAKIRLKFKEIQKSKEKLTTRVTEEEFCEAYSELCTRPEVYFLLVQ 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 167900458  324 ISKNKEYLDANDLMLFLEAEQGVTHITEDMCLDIIRRYELSEDGRQKGFLAIDGFTQYLLSPE 386
Cdd:cd16222    81 ISKNKEYLDAKDLMLFLEAEQGMTHITEEMCLDIIRRYEPSQEGRLKGFLGIDGFTQYLLSSE 143

C2_PLC_like

cd00275

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...

721-849

1.73e-59

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: 199.69 E-value: 1.73e-59

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  721 PLVLHIKIISGQNFPKPKGAcaKGDVIDPYVCVEIHGIPA-DCCEQRTKTVQQNSDNPIFDETFEFQVNLPELTMVRFVI 799
Cdd:cd00275     1 PLTLTIKIISGQQLPKPKGD--KGSIVDPYVEVEIHGLPAdDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVV 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 167900458  800 LDDDYIGDEFIGQYTIPFECLQPGYRHVPLRSFVGDIMEHVTLFVHIAIT 849
Cdd:cd00275    79 YDEDSGDDDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDIT 128

PH_PLC_eta

cd13364

Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of ...

116-224

1.65e-57

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: 193.27 E-value: 1.65e-57

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  116 MQAGCELKKVRPNSRIYNRFFTLDTDLQALRWEPSKKDLEKAKLDISAIKEIRLGKNTETFRNNGLADQICEDCAFSILH 195
Cdd:cd13364     1 MQEGSELVKVRSNSRQYRRFFYLDEDKSSIRWKPSKKKSEKAKIPISSIREVREGKTTDIFRSCDISGDFPEECCFSIIY 80

                          90       100
                  ....*....|....*....|....*....
gi 167900458  196 GENYESLDLVANSADVANIWVSGLRYLVS 224
Cdd:cd13364    81 GEEYETLDLVASSPDEANIWITGLRYLMS 109

Name

Accession

Description

Interval

E-value

PI-PLCc_PRIP_metazoa

cd08597

Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This ...

399-689

1.41e-166

Pssm-ID: 176539 [Multi-domain] Cd Length: 260 Bit Score: 490.78 E-value: 1.41e-166

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  399 QDMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGPDNEPILCNRNNMAMHLSFRSVLEVINK 478
Cdd:cd08597     2 QDMTQPLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDGPNGEPVIYHGHTLTSKISFRSVIEAINE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  479 FAFVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYTEAPLSSESYLPSPEKLKNMIIVKGKKLpsesdllegevtd 558
Cdd:cd08597    82 YAFVASEYPLILCIENHCSEKQQLVMAQYLKEIFGDKLYTEPPNEGESYLPSPHDLKGKIIIKGKKL------------- 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  559 edeeaemsrrmsgdyngeqKHIWLCRELSDLVSICKSVQHRDFELSMKTQNYWEMCSFSETEASRIANEYPEDFVNYNKK 638
Cdd:cd08597   149 -------------------KRRKLCKELSDLVSLCKSVRFQDFPTSAQNQKYWEVCSFSENLARRLANEFPEDFVNYNKK 209

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 167900458  639 FLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQN 689
Cdd:cd08597   210 FLSRVYPSPMRVDSSNYNPQDFWNCGCQIVAMNYQTPGLMMDLNTGKFLEN 260

EFh_PRIP1

cd16222

EF-hand motif found in phospholipase C-related but catalytically inactive protein 1 (PRIP-1); ...

244-386

3.36e-81

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: 260.95 E-value: 3.36e-81

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  244 WLKTVFEAADVDGNGIMLEDTSVELIKQLNPTLKESKIRLKFKEIQKSKEKLTTRVTEEEFCEAFCELCTRPEVYFLLVQ 323
Cdd:cd16222     1 WLSAVFEAADVDGYGIMLEDTAVELIKQLNPGIKEAKIRLKFKEIQKSKEKLTTRVTEEEFCEAYSELCTRPEVYFLLVQ 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 167900458  324 ISKNKEYLDANDLMLFLEAEQGVTHITEDMCLDIIRRYELSEDGRQKGFLAIDGFTQYLLSPE 386
Cdd:cd16222    81 ISKNKEYLDAKDLMLFLEAEQGMTHITEEMCLDIIRRYEPSQEGRLKGFLGIDGFTQYLLSSE 143

PI-PLC-X

pfam00388

Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...

401-542

9.16e-71

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: 232.01 E-value: 9.16e-71

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458   401 MTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGPDNEPILCNRNNMAMHLSFRSVLEVINKFA 480
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 167900458   481 FVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYTEAPLSSESYLPSPEKLKNMIIVKG 542
Cdd:pfam00388   81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLDDDLTELPSPEDLKGKILIKG 142

PLCXc

smart00148

Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...

401-543

1.73e-66

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: 219.84 E-value: 1.73e-66

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458    401 MTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGPDNEPILCNRNNMAMHLSFRSVLEVINKFA 480
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 167900458    481 FVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYTEAPLSSESYLPSPEKLKNMIIVKGK 543
Cdd:smart00148   81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSLEVLPSPEQLRGKILLKVR 143

PLN02228

Phosphoinositide phospholipase C

331-851

4.74e-66

Phosphoinositide phospholipase C

Pssm-ID: 177873 [Multi-domain] Cd Length: 567 Bit Score: 233.77 E-value: 4.74e-66

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  331 LDANDLMLFLEAEQGVTHITEDMCLDIIRRYELSEDGRQKGFLAIDGFTQYLLSpECDIFDPEQKKVAQDMTQPLSHYYI 410
Cdd:PLN02228   39 MSFDELLRFVSEVQGERHAGLDYVQDIFHSVKHHNVFHHHGLVHLNAFYRYLFS-DTNSPLPMSGQVHHDMKAPLSHYFV 117

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  411 NASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGPD-NEPILCNRNNMAMHLSFRSVLEVINKFAFVASEYPLI 489
Cdd:PLN02228  118 YTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSgNAAEVRHGRTLTSHEDLQKCLNAIKDNAFQVSDYPVV 197

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  490 LCLGNHCSLPQQKVMAQQMKKVFGEKLYTEAPLSSESYlPSPEKLKNMIIVKGK--KLPSESDLLEGEVTDEDEEAEMSR 567
Cdd:PLN02228  198 ITLEDHLPPNLQAQVAKMLTKTFRGMLFRCTSESTKHF-PSPEELKNKILISTKppKEYLESKTVQTTRTPTVKETSWKR 276

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  568 RMSGdyngEQKhiwLCRELSDLVSIckSVQHRDFeLSMKTQNY---WEMC-----------SFSETEASRIANEYPEDFV 633
Cdd:PLN02228  277 VADA----ENK---ILEEYKDEESE--AVGYRDL-IAIHAANCkdpLKDClsddpekpirvSMDEQWLETMVRTRGTDLV 346

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  634 NYNKKFLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQNGGCGYVLRPSIMRDEVSYFSANTK 713
Cdd:PLN02228  347 RFTQRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFNMQGHGKQLWIMQGMFRANGGCGYVKKPRILLDEHTLFDPCKR 426

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  714 giVPGVSPLVLHIKIISGQNFPKPKGACAKGDVIDPYVCVEIHGIPADCCEQRTKTvQQNSDNPIF-DETFEFQVNLPEL 792
Cdd:PLN02228  427 --LPIKTTLKVKIYTGEGWDLDFHLTHFDQYSPPDFFVKIGIAGVPRDTVSYRTET-AVDQWFPIWgNDEFLFQLRVPEL 503

                         490       500       510       520       530       540
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  793 TMVRFVILD-DDYIGDEFIGQYTIPFECLQPGYRHVPLRSFVGDIMEHVTLFVHIAITNR 851
Cdd:PLN02228  504 ALLWFKVQDyDNDTQNDFAGQTCLPLPELKSGVRAVRLHDRAGKAYKNTRLLVSFALDPP 563

C2_PLC_like

cd00275

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...

721-849

1.73e-59

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 199.69 E-value: 1.73e-59

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  721 PLVLHIKIISGQNFPKPKGAcaKGDVIDPYVCVEIHGIPA-DCCEQRTKTVQQNSDNPIFDETFEFQVNLPELTMVRFVI 799
Cdd:cd00275     1 PLTLTIKIISGQQLPKPKGD--KGSIVDPYVEVEIHGLPAdDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVV 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 167900458  800 LDDDYIGDEFIGQYTIPFECLQPGYRHVPLRSFVGDIMEHVTLFVHIAIT 849
Cdd:cd00275    79 YDEDSGDDDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDIT 128

PH_PLC_eta

cd13364

Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of ...

116-224

1.65e-57

Pssm-ID: 270170 Cd Length: 109 Bit Score: 193.27 E-value: 1.65e-57

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  116 MQAGCELKKVRPNSRIYNRFFTLDTDLQALRWEPSKKDLEKAKLDISAIKEIRLGKNTETFRNNGLADQICEDCAFSILH 195
Cdd:cd13364     1 MQEGSELVKVRSNSRQYRRFFYLDEDKSSIRWKPSKKKSEKAKIPISSIREVREGKTTDIFRSCDISGDFPEECCFSIIY 80

                          90       100
                  ....*....|....*....|....*....
gi 167900458  196 GENYESLDLVANSADVANIWVSGLRYLVS 224
Cdd:cd13364    81 GEEYETLDLVASSPDEANIWITGLRYLMS 109

PH_12

pfam16457

Pleckstrin homology domain;

111-224

1.66e-29

Pleckstrin homology domain;

Pssm-ID: 465123 [Multi-domain] Cd Length: 128 Bit Score: 113.89 E-value: 1.66e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458   111 DCISFMQAGCELKKVRPNSR-IYNRFFTLDTDLQALRWE---------PSKKDLEkAKLDISAIKEIRLGKNTETFRNNG 180
Cdd:pfam16457    4 QRLNCLLEGAWFPKVRGRRRkKKYRFCRLSPNRKVLHYGdfeekptvdPSLESLP-EKIDLSDIKEVVTGKECPHVRESG 82

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 167900458   181 -LADQICEDCAFSILHGE-NYESLDLVANSADVANIWVSGLRYLVS 224
Cdd:pfam16457   83 kKSKKTSSTLAFSLIYGAdEYELLDFVAPSESVAAIWLDGLNMLLG 128

smart00239

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...

723-829

5.46e-24

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: 97.17 E-value: 5.46e-24

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458    723 VLHIKIISGQNFPKPKgacaKGDVIDPYVCVEIHGipADCCEQRTKTVQqNSDNPIFDETFEFQVNLPELTMVRFVILDD 802
Cdd:smart00239    1 TLTVKIISARNLPPKD----KGGKSDPYVKVSLDG--DPKEKKKTKVVK-NTLNPVWNETFEFEVPPPELAELEIEVYDK 73

                            90       100
                    ....*....|....*....|....*...
gi 167900458    803 DYIG-DEFIGQYTIPFECLQPGYRHVPL 829
Cdd:smart00239   74 DRFGrDDFIGQVTIPLSDLLLGGRHEKL 101

pfam00168

C2 domain;

723-826

5.08e-19

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 83.14 E-value: 5.08e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458   723 VLHIKIISGQNFPKPKGacakGDVIDPYVCVEIHGipadcCEQRTKT-VQQNSDNPIFDETFEFQVNLPELTMVRFVILD 801
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDG----NGTSDPYVKVYLLD-----GKQKKKTkVVKNTLNPVWNETFTFSVPDPENAVLEIEVYD 72

                           90       100
                   ....*....|....*....|....*.
gi 167900458   802 DDYIG-DEFIGQYTIPFECLQPGYRH 826
Cdd:pfam00168   73 YDRFGrDDFIGEVRIPLSELDSGEGL 98

EF-hand_like

pfam09279

Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...

311-391

3.86e-12

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: 63.03 E-value: 3.86e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458   311 LCTRPEVYFLLVQISKNKEYLDANDLMLFLEAEQGVTHITEDMCLDIIRRYELSEDGRQKGFLAIDGFTQYLLSPECDIF 390
Cdd:pfam09279    5 LTQREEIDEIFQEYSGDGQKLSLDELVDFLREEQREEDASPALALSLIERYEPSETAKKQHAMTKDGFLMYLCSPDGSIF 84


                   .
gi 167900458   391 D 391
Cdd:pfam09279   85 N 85

COG5038

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];

724-823

1.14e-04

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 46.29 E-value: 1.14e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  724 LHIKIISGQNFPkpkgACAKGDVIDPYVCVEIHGIPAdcceQRTKTVQQNSdNPIFDETFEFQVNLPELTMVRFVILDDD 803
Cdd:COG5038  1042 LTIMLRSGENLP----SSDENGYSDPFVKLFLNEKSV----YKTKVVKKTL-NPVWNEEFTIEVLNRVKDVLTINVNDWD 1112

                          90       100
                  ....*....|....*....|.
gi 167900458  804 YIG-DEFIGQYTIPFECLQPG 823
Cdd:COG5038  1113 SGEkNDLLGTAEIDLSKLEPG 1133

PLN03008

Phospholipase D delta

748-873

7.42e-04

Phospholipase D delta

Pssm-ID: 178585 [Multi-domain] Cd Length: 868 Bit Score: 43.54 E-value: 7.42e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  748 DPYVCVeihgIPADCCEQRTKtVQQNSDNPIFDETFEFQVNLPeLTMVRFVILDDDYIGDEFIGQYTIPFECLQPGYR-- 825
Cdd:PLN03008   78 DPYVTV----VVPQATLARTR-VLKNSQEPLWDEKFNISIAHP-FAYLEFQVKDDDVFGAQIIGTAKIPVRDIASGERis 151

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 167900458  826 -HVPLRSFVGDIMEHVT-LFVHIAITN-------RSG-GGKPQKRSLS-----VRMGKKVREY 873
Cdd:PLN03008  152 gWFPVLGASGKPPKAETaIFIDMKFTPfdqihsyRCGiAGDPERRGVRrtyfpVRKGSQVRLY 214

Name

Accession

Description

Interval

E-value

PI-PLCc_PRIP_metazoa

cd08597

Catalytic domain of metazoan phospholipase C related, but catalytically inactive protein; This ...

399-689

1.41e-166

Pssm-ID: 176539 [Multi-domain] Cd Length: 260 Bit Score: 490.78 E-value: 1.41e-166

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  399 QDMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGPDNEPILCNRNNMAMHLSFRSVLEVINK 478
Cdd:cd08597     2 QDMTQPLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDGPNGEPVIYHGHTLTSKISFRSVIEAINE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  479 FAFVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYTEAPLSSESYLPSPEKLKNMIIVKGKKLpsesdllegevtd 558
Cdd:cd08597    82 YAFVASEYPLILCIENHCSEKQQLVMAQYLKEIFGDKLYTEPPNEGESYLPSPHDLKGKIIIKGKKL------------- 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  559 edeeaemsrrmsgdyngeqKHIWLCRELSDLVSICKSVQHRDFELSMKTQNYWEMCSFSETEASRIANEYPEDFVNYNKK 638
Cdd:cd08597   149 -------------------KRRKLCKELSDLVSLCKSVRFQDFPTSAQNQKYWEVCSFSENLARRLANEFPEDFVNYNKK 209

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 167900458  639 FLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQN 689
Cdd:cd08597   210 FLSRVYPSPMRVDSSNYNPQDFWNCGCQIVAMNYQTPGLMMDLNTGKFLEN 260

PI-PLCc_eukaryota

cd08558

Catalytic domain of eukaryotic phosphoinositide-specific phospholipase C and similar proteins; ...

399-689

4.02e-128

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: 389.12 E-value: 4.02e-128

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  399 QDMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGPDNEPILCNRNNMAMHLSFRSVLEVINK 478
Cdd:cd08558     2 QDMTQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGHTLTSKILFKDVIEAIKE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  479 FAFVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYTEAPLSSESYLPSPEKLKNMIIVKGKKlpsesdllegevtd 558
Cdd:cd08558    82 YAFVTSPYPVILSLENHCSLEQQKKMAQILKEIFGDKLLTPPLDENPVQLPSPEQLKGKILIKGKK-------------- 147

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  559 edeeaemsrrmsgdyngeqkhiwlcrelsdlvsicksvqhrdfelsmktqnyWEMCSFSETEASRIANEYPEDFVNYNKK 638
Cdd:cd08558   148 ----------------------------------------------------YHMSSFSETKALKLLKESPEEFVKYNKR 175

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 167900458  639 FLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQN 689
Cdd:cd08558   176 QLSRVYPKGTRVDSSNYNPQPFWNAGCQMVALNYQTPDLPMQLNQGKFEQN 226

PI-PLCc_delta

cd08593

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta; This subfamily ...

399-689

1.02e-115

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: 357.80 E-value: 1.02e-115

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  399 QDMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGPDNEPILCNRNNMAMHLSFRSVLEVINK 478
Cdd:cd08593     2 QDMTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDGPDGEPIIYHGHTLTSKILFKDVIQAIRE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  479 FAFVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYTEAPLSSESYLPSPEKLKNMIIVKGKKLPsesdllegevtd 558
Cdd:cd08593    82 YAFKVSPYPVILSLENHCSVEQQKVMAQHLKSILGDKLLTQPLDGVLTALPSPEELKGKILVKGKKLK------------ 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  559 edeeaemsrrmsgdyngeqkhiwLCRELSDLVSICKSVQHRDFELSMKTQNYWEMCSFSETEASRIANEYPEDFVNYNKK 638
Cdd:cd08593   150 -----------------------LAKELSDLVIYCKSVHFKSFEHSKENYHFYEMSSFSESKALKLAQESGNEFVRHNKR 206

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 167900458  639 FLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQN 689
Cdd:cd08593   207 QLSRIYPAGLRTDSSNYDPQEMWNVGCQIVALNFQTPGEEMDLNDGLFRQN 257

PI-PLCc_delta4

cd08631

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta4; This subfamily ...

399-689

1.95e-91

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: 293.39 E-value: 1.95e-91

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  399 QDMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGPDNEPILCNRNNMAMHLSFRSVLEVINK 478
Cdd:cd08631     2 QDMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDGPNGEPIVYHGHTFTSKILFKDVVAAVAQ 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  479 FAFVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYT-----EAPLSsesyLPSPEKLKNMIIVKGKKlpsesdlle 553
Cdd:cd08631    82 YAFQVSDYPVILSLENHCGVEQQQTMAQHLTEILGEKLLSttldgVLPTQ----LPSPEELRGKILLKGKK--------- 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  554 gevtdedeeaemsrrmsgdyngeqkhIWLCRELSDLVSICKSVQHRDFELSMKTQNYWEMCSFSETEASRIANEYPEDFV 633
Cdd:cd08631   149 --------------------------IRLSPELSDCVIYCKSVSFRSFTHSREHYHFYEISSFTETKARKLIREAGNEFV 202

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 167900458  634 NYNKKFLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQN 689
Cdd:cd08631   203 QHNTWQLSRVYPSGLRTDSSNYNPQEMWNAGCQMVALNFQTAGLEMDLNDGLFRQN 258

PI-PLCc_delta1

cd08629

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta1; This subfamily ...

399-689

2.05e-90

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: 290.40 E-value: 2.05e-90

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  399 QDMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGPDNEPILCNRNNMAMHLSFRSVLEVINK 478
Cdd:cd08629     2 QDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVLRAIRD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  479 FAFVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYTeAPLS-SESYLPSPEKLKNMIIVKGKKLPsesdllegevt 557
Cdd:cd08629    82 YAFKASPYPVILSLENHCSLEQQRVMARHLRAILGPILLD-QPLDgVTTSLPSPEQLKGKILLKGKKLK----------- 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  558 dedeeaemsrrmsgdyngeqkhiwLCRELSDLVSICKSVQHRDFELSMKT-QNYWEMCSFSETEASRIANEYPEDFVNYN 636
Cdd:cd08629   150 ------------------------LVPELSDMIIYCKSVHFGGFSSPGTSgQAFYEMASFSESRALRLLQESGNGFVRHN 205

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 167900458  637 KKFLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQN 689
Cdd:cd08629   206 VSCLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYLGCFQDN 258

PI-PLCc_gamma

cd08592

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma; This family ...

399-689

3.56e-87

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: 280.47 E-value: 3.56e-87

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  399 QDMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGPDNEPILCNRNNMAMHLSFRSVLEVINK 478
Cdd:cd08592     2 QDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGPDGMPIIYHGHTLTSKIKFMDVLKTIKE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  479 FAFVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYTEAPLSSESYLPSPEKLKNMIIVKGKKLpsesdllegevtd 558
Cdd:cd08592    82 HAFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDMLLTQPVDRNADQLPSPNQLKRKIIIKHKKL------------- 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  559 edeeaemsrrmsgdyngeqkhiwlcrelsdlvsicksvqhrdfelsmktqnYWEMCSFSETEASRIANE-YPEDFVNYNK 637
Cdd:cd08592   149 ---------------------------------------------------FYEMSSFPETKAEKYLNRqKGKIFLKYNR 177

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 167900458  638 KFLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQN 689
Cdd:cd08592   178 RQLSRVYPKGQRVDSSNYDPVPMWNCGSQMVALNFQTPDKPMQLNQALFMLN 229

PI-PLCc_delta3

cd08630

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-delta3; This subfamily ...

399-689

2.63e-85

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: 276.52 E-value: 2.63e-85

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  399 QDMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGPDNEPILCNRNNMAMHLSFRSVLEVINK 478
Cdd:cd08630     2 QDMSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVIQAVRQ 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  479 FAFVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYTEaPLSSES--YLPSPEKLKNMIIVKGKKLPsesdllegev 556
Cdd:cd08630    82 HAFTASPYPVILSLENHCGLEQQAAMARHLQTILGDMLVTQ-PLDSLNpeELPSPEELKGRVLVKGKKLQ---------- 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  557 tdedeeaemsrrmsgdyngeqkhiwLCRELSDLVSICKSVQHRDFELSMKTQNYWEMCSFSETEASRIANEYPEDFVNYN 636
Cdd:cd08630   151 -------------------------ISPELSALAVYCQATRLRTLEPAPVQPQPCQVSSLSERKAKKLIREAGNSFVRHN 205

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 167900458  637 KKFLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQN 689
Cdd:cd08630   206 ARQLTRVYPLGLRMNSANYSPQEMWNSGCQLVALNFQTPGYEMDLNAGRFLVN 258

PI-PLCc_beta

cd08591

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta; This subfamily ...

399-689

5.47e-84

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: 273.06 E-value: 5.47e-84

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  399 QDMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDG--PDNEPILCNRNNMAMHLSFRSVLEVI 476
Cdd:cd08591     2 QDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGkgEDEEPIITHGKTMCTEILFKDVIEAI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  477 NKFAFVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYTEA----PLSSESYLPSPEKLKNMIIVKGKKlpsesdll 552
Cdd:cd08591    82 AETAFKTSEYPVILSFENHCSSKQQAKMAEYCREIFGDLLLTEPlekyPLEPGVPLPSPNDLKRKILIKNKK-------- 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  553 egevtdedeeaemsrrmsgdyngeqkhiwlcreLSDLVSICKSVQHRDFELSMKTQNYWEMCSFSETEASRIANEYPEDF 632
Cdd:cd08591   154 ---------------------------------LSSLVNYIQPVKFQGFEVAEKRNKHYEMSSFNESKGLGYLKKSPIEF 200

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 167900458  633 VNYNKKFLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQN 689
Cdd:cd08591   201 VNYNKRQLSRIYPKGTRVDSSNYMPQIFWNAGCQMVALNFQTPDLPMQLNQGKFEYN 257

PI-PLCc_zeta

cd08595

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-zeta; This family ...

399-689

1.81e-83

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: 271.42 E-value: 1.81e-83

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  399 QDMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGPDNEPILCNRNNMAMHLSFRSVLEVINK 478
Cdd:cd08595     2 QDMDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDGADNEPVVYHGYTLTSKILFKEVITTVEK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  479 FAFVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYTeAPLS--SESYLPSPEKLKNMIIVKGKKLpsesdllegev 556
Cdd:cd08595    82 YAFEKSDYPVVLSLENHCSTEQQEIMAHYLVSILGEKLLR-APIDdpATGELPSPEALKFKILVKNKKK----------- 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  557 tdedeeaemsrrmsgdyngeqkhiwLCRELSDLVSICKSVQHRDFELSMKTQNYWEMCSFSETEASRIANEYPEDFVNYN 636
Cdd:cd08595   150 -------------------------IAKALSDLVIYTKSEKFCSFTHSRDNQHSYENNSIGENKARKLLKSSGADFVGHT 204

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 167900458  637 KKFLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQN 689
Cdd:cd08595   205 QRFITRIYPKGTRASSSNYNPQEFWNVGCQMVALNFQTLGAPMDLQNGKFLDN 257

PI-PLCc_eta2

cd08633

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta2; This subfamily ...

399-689

7.07e-83

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: 269.99 E-value: 7.07e-83

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  399 QDMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGPDNEPILCNRNNMAMHLSFRSVLEVINK 478
Cdd:cd08633     2 QDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  479 FAFVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYTEAPLSSES-YLPSPEKLKNMIIVKGKKLPsesdllegevt 557
Cdd:cd08633    82 YAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLDLSSVISNDCtRLPSPEILKGKILVKGKKLS----------- 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  558 dedeeaemsrrmsgdyngeqkhiwlcRELSDLVSICKSVQHRDFElsMKTQNYWEMCSFSETEASRIANEYPEDFVNYNK 637
Cdd:cd08633   151 --------------------------RALSDLVKYTKSVRVHDIE--TEATSSWQVSSFSETKAHQILQQKPAQYLRFNQ 202

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 167900458  638 KFLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQN 689
Cdd:cd08633   203 RQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKFSAN 254

PI-PLC1c_yeast

cd08598

Catalytic domain of putative yeast phosphatidylinositide-specific phospholipases C; This ...

399-689

1.32e-81

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

Pssm-ID: 176540 [Multi-domain] Cd Length: 231 Bit Score: 265.26 E-value: 1.32e-81

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  399 QDMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGPDNEPILCNRNNMAMHLSFRSVLEVINK 478
Cdd:cd08598     2 EDLSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDGDDGEPVVTHGYTLTSSVPFRDVCRAIKK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  479 FAFVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYTEAPLSSESYLPSPEKLKNMIIVKGKKLPsesdllegevtd 558
Cdd:cd08598    82 YAFVTSPYPLILSLEVHCDAEQQERMVEIMKETFGDLLVTEPLDGLEDELPSPEELRGKILIKVKKES------------ 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  559 edeeaemsrrmsgdyngeqkhiwlcrelsdlvsicKSVQHrdfelsmktqnyweMCSFSETEASRIANEYPEDFVNYNKK 638
Cdd:cd08598   150 -----------------------------------KTPNH--------------IFSLSERSLLKLLKDKRAALDKHNRR 180

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|.
gi 167900458  639 FLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQN 689
Cdd:cd08598   181 HLMRVYPSGTRISSSNFNPLPFWRAGVQMVALNWQTYDLGMQLNEAMFAGS 231

PI-PLCc_eta

cd08594

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta; This family ...

399-689

2.18e-81

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: 264.74 E-value: 2.18e-81

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  399 QDMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGPDNEPILCNRNNMAMHLSFRSVLEVINK 478
Cdd:cd08594     2 QDMTQPLSHYFIASSHNTYLTGDQLLSQSRVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKILFRDVIETINK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  479 FAFVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYTEAPLSSESY-LPSPEKLKNMIIVKGKKlpsesdllegevt 557
Cdd:cd08594    82 YAFIKNEYPVILSIENHCSVQQQKKMAQYLKEILGDKLDLSSVISGDSKqLPSPQSLKGKILIKGKK------------- 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  558 dedeeaemsrrmsgdyngeqkhiwlcrelsdlvsicksvqhrdfelsmktqnyWEMCSFSETEASRIANEYPEDFVNYNK 637
Cdd:cd08594   149 -----------------------------------------------------WQVSSFSETRAHQIVQQKAAQFLRFNQ 175

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 167900458  638 KFLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQN 689
Cdd:cd08594   176 RQLSRIYPSAYRIDSSNFNPQPYWNAGCQLVALNYQTEGRMLQLNRAKFRAN 227

EFh_PRIP1

cd16222

EF-hand motif found in phospholipase C-related but catalytically inactive protein 1 (PRIP-1); ...

244-386

3.36e-81

Pssm-ID: 320052 [Multi-domain] Cd Length: 143 Bit Score: 260.95 E-value: 3.36e-81

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  244 WLKTVFEAADVDGNGIMLEDTSVELIKQLNPTLKESKIRLKFKEIQKSKEKLTTRVTEEEFCEAFCELCTRPEVYFLLVQ 323
Cdd:cd16222     1 WLSAVFEAADVDGYGIMLEDTAVELIKQLNPGIKEAKIRLKFKEIQKSKEKLTTRVTEEEFCEAYSELCTRPEVYFLLVQ 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 167900458  324 ISKNKEYLDANDLMLFLEAEQGVTHITEDMCLDIIRRYELSEDGRQKGFLAIDGFTQYLLSPE 386
Cdd:cd16222    81 ISKNKEYLDAKDLMLFLEAEQGMTHITEEMCLDIIRRYEPSQEGRLKGFLGIDGFTQYLLSSE 143

PI-PLCc_eta1

cd08632

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-eta1; This subfamily ...

399-689

3.15e-79

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: 259.96 E-value: 3.15e-79

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  399 QDMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGPDNEPILCNRNNMAMHLSFRSVLEVINK 478
Cdd:cd08632     2 QDMDQPLCNYFIASSHNTYLTGDQLLSQSKVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKITFRDVIETINK 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  479 FAFVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYTEAPLSSES-YLPSPEKLKNMIIVKGKKLpsesdllegevt 557
Cdd:cd08632    82 YAFVKNEFPVILSIENHCSIQQQKKIAQYLKEIFGDKLDLSSVLTGDPkQLPSPQLLKGKILVKGKKL------------ 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  558 dedeeaemsrrmsgdyngeqkhiwlCRELSDLVSICKSVQHRDFELSMKTQNyweMCSFSETEASRIANEYPEDFVNYNK 637
Cdd:cd08632   150 -------------------------CRDLSDLVVYTNSVAAQDIVDDGSTGN---VLSFSETRAHQLVQQKAEQFMTYNQ 201

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 167900458  638 KFLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQN 689
Cdd:cd08632   202 KQLTRIYPSAYRIDSSNFNPLPYWNVGCQLVALNYQSEGRMMQLNRAKFMVN 253

PI-PLCc_gamma2

cd08628

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma2; This subfamily ...

399-689

9.54e-75

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: 247.66 E-value: 9.54e-75

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  399 QDMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGPDNEPILCNRNNMAMHLSFRSVLEVINK 478
Cdd:cd08628     2 QDMNNPLSHYWISSSHNTYLTGDQLRSESSTEAYIRCLRMGCRCIELDCWDGPDGKPIIYHGWTRTTKIKFDDVVQAIKD 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  479 FAFVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYTEAPLSSESYLPSPEKLKNMIIVKGKKLpsesdllegevtd 558
Cdd:cd08628    82 HAFVTSEYPVILSIEEHCSVEQQRHMAKVFKEVFGDKLLMKPLEASADQLPSPTQLKEKIIIKHKKL------------- 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  559 edeeaemsrrmsgdyngeqkhiwLCRELSDLVSICK-SVQHRDfelSMKTQNYWEMCSFSETEASRIANEYPEDFVNYNK 637
Cdd:cd08628   149 -----------------------IAIELSDLVVYCKpTSKTKD---NLENPDFKEIRSFVETKAPSIIRQKPVQLLKYNR 202

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 167900458  638 KFLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQN 689
Cdd:cd08628   203 KGLTRVYPKGQRVDSSNYDPFRLWLCGSQMVALNFQTADKYMQLNHALFSLN 254

PI-PLCc_epsilon

cd08596

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-epsilon; This family ...

399-689

1.77e-72

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: 241.29 E-value: 1.77e-72

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  399 QDMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGPDNEPILCNRNNMAMHLSFRSVLEVINK 478
Cdd:cd08596     2 EDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGDDGMPIIYHGHTLTTKIPFKDVVEAINR 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  479 FAFVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYT----EAPLSSESYLPSPEKLKNMIIVKGKKLPsesdlleg 554
Cdd:cd08596    82 SAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLVTkflfESDFSDDPSLPSPLQLKNKILLKNKKAP-------- 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  555 evtdedeeaemsrrmsgdyngeqkhiwlcrELSDLVSICKSVQHRDFelsmKTQNYWEMCSFSETEASRIANEYPEDFVN 634
Cdd:cd08596   154 ------------------------------ELSDLVIYCQAVKFPGL----STPKCYHISSLNENAAKRLCRRYPQKLVQ 199

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 167900458  635 YNKKFLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQN 689
Cdd:cd08596   200 HTRCQLLRTYPAATRIDSSNPNPLIFWLHGLQLVALNYQTDDLPMHLNAAMFEAN 254

PI-PLC-X

pfam00388

Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to ...

401-542

9.16e-71

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: 232.01 E-value: 9.16e-71

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458   401 MTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGPDNEPILCNRNNMAMHLSFRSVLEVINKFA 480
Cdd:pfam00388    1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 167900458   481 FVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYTEAPLSSESYLPSPEKLKNMIIVKG 542
Cdd:pfam00388   81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLDDDLTELPSPEDLKGKILIKG 142

PI-PLCc_beta4

cd08626

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta4; This subfamily ...

398-689

1.35e-70

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: 236.20 E-value: 1.35e-70

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  398 AQDMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGP--DNEPILCNRNNMAMHLSFRSVLEV 475
Cdd:cd08626     1 YQDMDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGKgeDQEPIITHGKAMCTDILFKDVIQA 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  476 INKFAFVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYTEA----PLSSESYLPSPEKLKNMIIVKGKKlpsesdl 551
Cdd:cd08626    81 IKDTAFVTSDYPVILSFENHCSKPQQYKLAKYCEEIFGDLLLTKPleshPLEPGVPLPSPNKLKRKILIKNKR------- 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  552 legevtdedeeaemsrrmsgdyngeqkhiwlcreLSDLVSICKSVQHRDFELSMKTQNYWEMCSFSETEASRIANEYPED 631
Cdd:cd08626   154 ----------------------------------LSSLVNYAQPVKFQGFDVAEERNIHFNMSSFNESVGLGYLKTSAIE 199

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 167900458  632 FVNYNKKFLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQN 689
Cdd:cd08626   200 FVNYNKRQMSRIYPKGTRVDSSNYMPQIFWNAGCQMVSLNFQTPDLGMQLNQGKFEYN 257

EFh_PRIP

cd16206

EF-hand motif found in phospholipase C-related but catalytically inactive proteins (PRIP); ...

244-386

8.10e-68

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: 223.63 E-value: 8.10e-68

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  244 WLKTVFEAADVDGNGIMLEDTSVELIKQLNPTLKESKIRLKFKEIQKSKEKLTTRVTEEEFCEAFCELCTRPEVYFLLVQ 323
Cdd:cd16206     1 WLESVFEEADTNKSGFLDEEEAVQLIKQLNPGLSTSRIKQKLKELQKKKDGARGRVSSDEFVELFKELATRPEIYFLLVR 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 167900458  324 ISKNKEYLDANDLMLFLEAEQGVTHITEDMCLDIIRRYELSEDGRQKGFLAIDGFTQYLLSPE 386
Cdd:cd16206    81 YASNKDYLTVDDLMLFLEAEQGMTGVTKEKCLEIINKYEPSEEGREKGQLGIDGFTRYLLSEE 143

PI-PLCc_gamma1

cd08627

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-gamma1; This subfamily ...

399-689

1.59e-66

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: 223.75 E-value: 1.59e-66

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  399 QDMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGPDNEPILCNRNNMAMHLSFRSVLEVINK 478
Cdd:cd08627     2 EEMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  479 FAFVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYTEAPLSSESYLPSPEKLKNMIIVKGKKLpsesdllegevtd 558
Cdd:cd08627    82 HAFVTSEYPIILSIEDHCSIVQQRNMAQHFKKVFGDMLLTKPVDINADGLPSPNQLKRKILIKHKKL------------- 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  559 edeeaemsrrmsgdyngeqkhiwlcrelsdlvsicksvqhrdfelsmktqnYWEMCSFSETEASRIANEYP-EDFVNYNK 637
Cdd:cd08627   149 ---------------------------------------------------YRDMSSFPETKAEKYVNRSKgKKFLQYNR 177

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 167900458  638 KFLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQN 689
Cdd:cd08627   178 RQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFMLG 229

PLCXc

smart00148

Phospholipase C, catalytic domain (part); domain X; Phosphoinositide-specific phospholipases C. ...

401-543

1.73e-66

Pssm-ID: 197543 [Multi-domain] Cd Length: 143 Bit Score: 219.84 E-value: 1.73e-66

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458    401 MTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGPDNEPILCNRNNMAMHLSFRSVLEVINKFA 480
Cdd:smart00148    1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                            90       100       110       120       130       140
                    ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 167900458    481 FVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYTEAPLSSESYLPSPEKLKNMIIVKGK 543
Cdd:smart00148   81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSLEVLPSPEQLRGKILLKVR 143

PLN02228

Phosphoinositide phospholipase C

331-851

4.74e-66

Phosphoinositide phospholipase C

Pssm-ID: 177873 [Multi-domain] Cd Length: 567 Bit Score: 233.77 E-value: 4.74e-66

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  331 LDANDLMLFLEAEQGVTHITEDMCLDIIRRYELSEDGRQKGFLAIDGFTQYLLSpECDIFDPEQKKVAQDMTQPLSHYYI 410
Cdd:PLN02228   39 MSFDELLRFVSEVQGERHAGLDYVQDIFHSVKHHNVFHHHGLVHLNAFYRYLFS-DTNSPLPMSGQVHHDMKAPLSHYFV 117

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  411 NASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGPD-NEPILCNRNNMAMHLSFRSVLEVINKFAFVASEYPLI 489
Cdd:PLN02228  118 YTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSgNAAEVRHGRTLTSHEDLQKCLNAIKDNAFQVSDYPVV 197

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  490 LCLGNHCSLPQQKVMAQQMKKVFGEKLYTEAPLSSESYlPSPEKLKNMIIVKGK--KLPSESDLLEGEVTDEDEEAEMSR 567
Cdd:PLN02228  198 ITLEDHLPPNLQAQVAKMLTKTFRGMLFRCTSESTKHF-PSPEELKNKILISTKppKEYLESKTVQTTRTPTVKETSWKR 276

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  568 RMSGdyngEQKhiwLCRELSDLVSIckSVQHRDFeLSMKTQNY---WEMC-----------SFSETEASRIANEYPEDFV 633
Cdd:PLN02228  277 VADA----ENK---ILEEYKDEESE--AVGYRDL-IAIHAANCkdpLKDClsddpekpirvSMDEQWLETMVRTRGTDLV 346

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  634 NYNKKFLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQNGGCGYVLRPSIMRDEVSYFSANTK 713
Cdd:PLN02228  347 RFTQRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFNMQGHGKQLWIMQGMFRANGGCGYVKKPRILLDEHTLFDPCKR 426

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  714 giVPGVSPLVLHIKIISGQNFPKPKGACAKGDVIDPYVCVEIHGIPADCCEQRTKTvQQNSDNPIF-DETFEFQVNLPEL 792
Cdd:PLN02228  427 --LPIKTTLKVKIYTGEGWDLDFHLTHFDQYSPPDFFVKIGIAGVPRDTVSYRTET-AVDQWFPIWgNDEFLFQLRVPEL 503

                         490       500       510       520       530       540
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  793 TMVRFVILD-DDYIGDEFIGQYTIPFECLQPGYRHVPLRSFVGDIMEHVTLFVHIAITNR 851
Cdd:PLN02228  504 ALLWFKVQDyDNDTQNDFAGQTCLPLPELKSGVRAVRLHDRAGKAYKNTRLLVSFALDPP 563

PI-PLCc_beta3

cd08625

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta3; This subfamily ...

400-689

9.96e-66

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: 222.62 E-value: 9.96e-66

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  400 DMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDG--PDNEPILCNRNNMAMHLSFRSVLEVIN 477
Cdd:cd08625     3 DMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGrpPEEEPFITHGFTMTTEIPFKDVIEAIA 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  478 KFAFVASEYPLILCLGNHC-SLPQQKVMAQQMKKVFGEKLYTEA----PLSSESYLPSPEKLKNMIIVKGKKlpsesdll 552
Cdd:cd08625    83 ESAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPldkyPLVPGVQLPSPQELMGKILVKNKK-------- 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  553 egevtdedeeaemsrrmsgdyngeqkhiwlcreLSDLVSICKSVQHRDFELSMKTQNYWEMCSFSETEASRIANEYPEDF 632
Cdd:cd08625   155 ---------------------------------MSTLVNYIEPVKFKSFEAAAKRNKFFEMSSFVETKAMEQLTKSPMEF 201

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 167900458  633 VNYNKKFLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQN 689
Cdd:cd08625   202 VEYNKKQLSRIYPKGTRVDSSNYMPQLFWNVGCQMVALNFQTLDLAMQLNMGVFEYN 258

PI-PLCc_beta2

cd08624

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta2; This subfamily ...

399-681

3.00e-63

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: 215.69 E-value: 3.00e-63

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  399 QDMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDG--PDNEPILCNRNNMAMHLSFRSVLEVI 476
Cdd:cd08624     2 QDMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTEILFKDAIEAI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  477 NKFAFVASEYPLILCLGNHCSLP-QQKVMAQQMKKVFGEKLYTEA----PLSSESYLPSPEKLKNMIIVKGKKLpsesdl 551
Cdd:cd08624    82 AESAFKTSPYPVILSFENHVDSPkQQAKMAEYCRTIFGDMLLTEPlekyPLKPGVPLPSPEDLRGKILIKNKKY------ 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  552 legevtdedeeaemsrrmsgdyngeqkhiwlcRELSDLVSICKSVQHRDFELSMKTQNYWEMCSFSETEASRIANEYPED 631
Cdd:cd08624   156 --------------------------------EEMSSLVNYIQPTKFVSFEFSAQKNRSYVISSFTELKAYDLLSKASVQ 203

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|
gi 167900458  632 FVNYNKKFLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTpgpmMDL 681
Cdd:cd08624   204 FVEYNKRQMSRIYPKGTRMDSSNYMPQMFWNVGCQMVALNFQT----MDL 249

PLCYc

smart00149

Phospholipase C, catalytic domain (part); domain Y; Phosphoinositide-specific phospholipases C. ...

587-701

6.19e-60

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: 200.54 E-value: 6.19e-60

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458    587 SDLVSICKSVQHRDFELSMKTQNYWEMCSFSETEASRIANEYPEDFVNYNKKFLSRVYPSAMRIDSSNLNPQDFWNCGCQ 666
Cdd:smart00149    1 SDLVIYCAPVKFRSFESAESKNPFYEMSSFSETKAKKLLKKSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGCQ 80

                            90       100       110
                    ....*....|....*....|....*....|....*
gi 167900458    667 IVAMNFQTPGPMMDLHTGWFLQNGGCGYVLRPSIM 701
Cdd:smart00149   81 MVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115

C2_PLC_like

cd00275

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in ...

721-849

1.73e-59

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 199.69 E-value: 1.73e-59

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  721 PLVLHIKIISGQNFPKPKGAcaKGDVIDPYVCVEIHGIPA-DCCEQRTKTVQQNSDNPIFDETFEFQVNLPELTMVRFVI 799
Cdd:cd00275     1 PLTLTIKIISGQQLPKPKGD--KGSIVDPYVEVEIHGLPAdDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVV 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 167900458  800 LDDDYIGDEFIGQYTIPFECLQPGYRHVPLRSFVGDIMEHVTLFVHIAIT 849
Cdd:cd00275    79 YDEDSGDDDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDIT 128

PI-PLCc_beta1

cd08623

Catalytic domain of metazoan phosphoinositide-specific phospholipase C-beta1; This subfamily ...

399-689

4.74e-58

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: 200.69 E-value: 4.74e-58

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  399 QDMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDG--PDNEPILCNRNNMAMHLSFRSVLEVI 476
Cdd:cd08623     2 EDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGrtAEEEPVITHGFTMTTEISFKEVIEAI 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  477 NKFAFVASEYPLILCLGNHCSLP-QQKVMAQQMKKVFGEKLYTEA----PLSSESYLPSPEKLKNMIIVKGKKlpsesdl 551
Cdd:cd08623    82 AECAFKTSPFPILLSFENHVDSPkQQAKMAEYCRLIFGDALLMEPlekyPLESGVPLPSPMDLMYKILVKNKK------- 154

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  552 legevtdedeeaemsrrmsgdyngeqkhiwlcreLSDLVSICKSVQHRDFELSMKTQNYWEMCSFSETEASRIANEYPED 631
Cdd:cd08623   155 ----------------------------------MSNLVNYIQPVKFESFEASKKRNKSFEMSSFVETKGLEQLTKSPVE 200

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 167900458  632 FVNYNKKFLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQN 689
Cdd:cd08623   201 FVEYNKMQLSRIYPKGTRVDSSNYMPQLFWNAGCQMVALNFQTVDLSMQINMGMYEYN 258

PH_PLC_eta

cd13364

Phospholipase C-eta (PLC-eta) pleckstrin homology (PH) domain; PLC-eta (PLCeta) consists of ...

116-224

1.65e-57

Pssm-ID: 270170 Cd Length: 109 Bit Score: 193.27 E-value: 1.65e-57

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  116 MQAGCELKKVRPNSRIYNRFFTLDTDLQALRWEPSKKDLEKAKLDISAIKEIRLGKNTETFRNNGLADQICEDCAFSILH 195
Cdd:cd13364     1 MQEGSELVKVRSNSRQYRRFFYLDEDKSSIRWKPSKKKSEKAKIPISSIREVREGKTTDIFRSCDISGDFPEECCFSIIY 80

                          90       100
                  ....*....|....*....|....*....
gi 167900458  196 GENYESLDLVANSADVANIWVSGLRYLVS 224
Cdd:cd13364    81 GEEYETLDLVASSPDEANIWITGLRYLMS 109

PLN02952

phosphoinositide phospholipase C

316-844

1.80e-57

phosphoinositide phospholipase C

Pssm-ID: 178538 [Multi-domain] Cd Length: 599 Bit Score: 209.85 E-value: 1.80e-57

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  316 EVYFLLVQISKNKEYLDANDLMLFLEAEQGVTHIT----EDMCLDII-RRYELSEDGRQKgfLAIDGFTQYLLSPecDIF 390
Cdd:PLN02952   39 DVKDVFCKFSVGGGHMGADQLRRFLVLHQDELDCTlaeaQRIVEEVInRRHHVTRYTRHG--LNLDDFFHFLLYD--DLN 114

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  391 DPEQKKVAQDMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGPDNEPILC-NRNNMAMHLSF 469
Cdd:PLN02952  115 GPITPQVHHDMTAPLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPGSTKDEILVlHGRTLTTPVPL 194

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  470 RSVLEVINKFAFVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYTEaplSSESYL--PSPEKLKNMIIVKGKKlPS 547
Cdd:PLN02952  195 IKCLKSIRDYAFSSSPYPVIITLEDHLTPDLQAKVAEMATQIFGQMLYYP---ESDSLVqfPSPESLKHRIIISTKP-PK 270

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  548 EsdLLEG-----------------EVTDEDEEA----------EMSRRMSGDYNGEQKHIWLCRELSDLVSICKSVQHRD 600
Cdd:PLN02952  271 E--YLESsgpivikkknnvspsgrNSSEETEEAqtlesmlfeqEADSRSDSDQDDNKSGELQKPAYKRLITIHAGKPKGT 348

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  601 FELSMKTQ-NYWEMCSFSETEASRIANEYPEDFVNYNKKFLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMM 679
Cdd:PLN02952  349 LKDAMKVAvDKVRRLSLSEQELEKAATTNGQDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQGYGKSL 428

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  680 DLHTGWFLQNGGCGYVLRPSIM-----RDEVsyFSANTKGIVPGvsplVLHIKIISGQNFpKPKGACAKGDVIDP---YV 751
Cdd:PLN02952  429 WLMHGMFRANGGCGYLKKPDFLmkkgfHDEV--FDPKKKLPVKK----TLKVKVYLGDGW-RLDFSHTHFDSYSPpdfYT 501

                         490       500       510       520       530       540       550       560
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  752 CVEIHGIPADCCEQRTKTVQQNSdNPIFDETFEFQVNLPELTMVRFVILDDDYI-GDEFIGQYTIPFECLQPGYRHVPLR 830
Cdd:PLN02952  502 KMYIVGVPADNAKKKTKIIEDNW-YPAWNEEFSFPLTVPELALLRIEVREYDMSeKDDFGGQTCLPVSELRPGIRSVPLH 580

                         570
                  ....*....|....
gi 167900458  831 SFVGDIMEHVTLFV 844
Cdd:PLN02952  581 DKKGEKLKNVRLLM 594

PI-PLC-Y

pfam00387

Phosphatidylinositol-specific phospholipase C, Y domain; This associates with pfam00388 to ...

586-699

5.01e-56

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

Pssm-ID: 459794 Cd Length: 114 Bit Score: 189.21 E-value: 5.01e-56

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458   586 LSDLVSICKSVQHRDFELSmKTQNYWEMCSFSETEASRIANEYPEDFVNYNKKFLSRVYPSAMRIDSSNLNPQDFWNCGC 665
Cdd:pfam00387    1 LSDLVVYTQSVKFKSFSTP-ESKTPNHIFSFSESKALKLIKSSSAAFVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNCGV 79

                           90       100       110
                   ....*....|....*....|....*....|....
gi 167900458   666 QIVAMNFQTPGPMMDLHTGWFLQNGGCGYVLRPS 699
Cdd:pfam00387   80 QMVALNWQTPDEGMQLNEGMFADNGGCGYVLKPE 113

EFh_PRIP2

cd16223

EF-hand motif found in phospholipase C-related but catalytically inactive protein 2 (PRIP-2); ...

244-387

1.13e-55

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: 189.35 E-value: 1.13e-55

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  244 WLKTVFEAADVDGNGIMLEDTSVELIKQLNPTLKESKIRLKFKEIQKSKEKLTTRVTEEEFCEAFCELCTRPEVYFLLVQ 323
Cdd:cd16223     1 WLSQMFVEADTDNVGHITLCRAVQFIKNLNPGLKTSKIELKFKELHKSKEKGGTEVTKEEFIEVFHELCTRPEIYFLLVQ 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 167900458  324 ISKNKEYLDANDLMLFLEAEQGVTHITEDMCLDIIRRYELSEDGRQKGFLAIDGFTQYLLSPEC 387
Cdd:cd16223    81 FSSNKEFLDTKDLMMFLEAEQGMAHVTEEISLDIIHKYEPSKEGQEKGWLSLDGFTNYLMSPEC 144

PI-PLCc_plant

cd08599

Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family ...

399-689

3.21e-54

Catalytic domain of plant phosphatidylinositide-specific phospholipases C; This family corresponds to the catalytic domain present in a group of phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11) encoded by PLC genes from higher plants, which are homologs of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The domain arrangement of plant PI-PLCs is structurally similar to the mammalian PLC-zeta isoform, which lacks the N-terminal pleckstrin homology (PH) domain, but contains EF-hand like motifs (which are absent in a few plant PLCs), a PLC catalytic core domain with X- and Y- highly conserved regions split by a linker sequence, and a C2 domain. However, at the sequence level, the plant PI-PLCs are closely related to the mammalian PLC-delta isoform. Experiments show that plant PLCs display calcium dependent PLC catalytic properties, although they lack some of the N-terminal motifs found in their mammalian counterparts. A putative calcium binding site may be located at the region spanning the X- and Y- domains.

Pssm-ID: 176541 [Multi-domain] Cd Length: 228 Bit Score: 188.73 E-value: 3.21e-54

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  399 QDMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGPDNEPILCNRNNMAMHLSFRSVLEVINK 478
Cdd:cd08599     2 HDMTAPLSHYFIFSSHNSYLTGNQLSSRSSTAPIIEALLRGCRVIELDLWPGGRGDICVLHGGTLTKPVKFEDCIKAIKE 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  479 FAFVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYTEAPLSSESYLPSPEKLKNMIIVKgKKLPSesdllegevtd 558
Cdd:cd08599    82 NAFTASEYPVIITLENHLSPELQAKAAQILRETLGDKLFYPDSEDLPEEFPSPEELKGKILIS-DKPPV----------- 149

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  559 edeeaemsrrmsgdyngeqkhiwlcrelsdlvsicksvqhrdfelsmktqnywEMCSFSET-EASRIANEYPEDFVNYNK 637
Cdd:cd08599   150 -----------------------------------------------------IRNSLSETqLKKVIEGEHPTDLIEFTQ 176

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|..
gi 167900458  638 KFLSRVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQN 689
Cdd:cd08599   177 KNLLRVYPAGLRITSSNYDPMLAWMHGAQMVALNMQGYDRPLWLNRGKFRAN 228

PLN02222

phosphoinositide phospholipase C 2

373-846

1.08e-53

phosphoinositide phospholipase C 2

Pssm-ID: 177868 [Multi-domain] Cd Length: 581 Bit Score: 198.33 E-value: 1.08e-53

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  373 LAIDGFTQYLLSpecDIFDP-EQKKVAQDMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKMGCRSIELDVSDGP 451
Cdd:PLN02222   79 LHLDAFFKYLFG---DNNPPlALHEVHHDMDAPISHYFIFTGHNSYLTGNQLSSDCSEVPIIDALKKGVRVIELDIWPNS 155

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  452 DNEPI-LCNRNNMAMHLSFRSVLEVINKFAFVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYTeaPLSSESY--L 528
Cdd:PLN02222  156 DKDDIdVLHGMTLTTPVGLIKCLKAIRAHAFDVSDYPVVVTLEDHLTPDLQSKVAEMVTEIFGEILFT--PPVGESLkeF 233

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  529 PSPEKLKNMIIVK----------------------------GKKLPS--------ESDLLEGEVTDEDEEAEMSRRMSGD 572
Cdd:PLN02222  234 PSPNSLKKRIIIStkppkeykegkddevvqkgkdlgdeevwGREVPSfiqrnksvDKNDSNGDDDDDDDDGEDKSKKNAP 313

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  573 ynGEQKHiwlcrelsdLVSICKSVQHRDFELSMKTQ-NYWEMCSFSETEASRIANEYPEDFVNYNKKFLSRVYPSAMRID 651
Cdd:PLN02222  314 --PQYKH---------LIAIHAGKPKGGITECLKVDpDKVRRLSLSEEQLEKAAEKYAKQIVRFTQHNLLRIYPKGTRVT 382

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  652 SSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQNGGCGYVLRPS-IMRDEVSYFSANTKGIVPGVSPLVLHIKIIS 730
Cdd:PLN02222  383 SSNYNPLVGWSHGAQMVAFNMQGYGRSLWLMQGMFRANGGCGYIKKPDlLLKSGSDSDIFDPKATLPVKTTLRVTIYMGE 462

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  731 GQNFPKPKGACAKGDVIDPYVCVEIHGIPADCCEQRTKTVQQNSDnPIFDETFEFQVNLPELTMVRFVILDDDYI-GDEF 809
Cdd:PLN02222  463 GWYFDFRHTHFDQYSPPDFYTRVGIAGVPGDTVMKKTKTLEDNWI-PAWDEVFEFPLTVPELALLRLEVHEYDMSeKDDF 541

                         490       500       510
                  ....*....|....*....|....*....|....*..
gi 167900458  810 IGQYTIPFECLQPGYRHVPLRSFVGDIMEHVTLFVHI 846
Cdd:PLN02222  542 GGQTCLPVWELSQGIRAFPLHSRKGEKYKSVKLLVKV 578

PLN02230

phosphoinositide phospholipase C 4

359-829

7.89e-47

phosphoinositide phospholipase C 4

Pssm-ID: 177875 [Multi-domain] Cd Length: 598 Bit Score: 177.97 E-value: 7.89e-47

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  359 RRYELSEDGRQKgfLAIDGFTQYLLSpeCDIFDPEQKKVAQDMTQPLSHYYINASHNTYLIEDQFRGPADINGYVRALKM 438
Cdd:PLN02230   79 RKHHIAKFTRRN--LTLDDFNYYLFS--TDLNPPIADQVHQNMDAPLSHYFIFTGHNSYLTGNQLSSNCSELPIADALRR 154

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  439 GCRSIELDVSDGPDNEPILCNRNNMAMHLSFRSVLEVINKFAFVASEYPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYT 518
Cdd:PLN02230  155 GVRVVELDLWPRGTDDVCVKHGRTLTKEVKLGKCLDSIKANAFAISKYPVIITLEDHLTPKLQFKVAKMITQTFGDMLYY 234

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  519 EAPLSSESYlPSPEKLKNMIIVKGKKlPSEsdLLEGEVTDEDEEAEMSRRMSGDYNGEQKHIWLCRElSDLVSICKSVQ- 597
Cdd:PLN02230  235 HDSEGCQEF-PSPEELKEKILISTKP-PKE--YLEANDAKEKDNGEKGKDSDEDVWGKEPEDLISTQ-SDLDKVTSSVNd 309

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  598 -----------HRDFELSMKTQNYWEMC-------------------------SFSETEASRIANEYPEDFVNYNKKFLS 641
Cdd:PLN02230  310 lnqddeergscESDTSCQLQAPEYKRLIaihagkpkgglrmalkvdpnkirrlSLSEQLLEKAVASYGADVIRFTQKNFL 389

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  642 RVYPSAMRIDSSNLNPQDFWNCGCQIVAMNFQTPGPMMDLHTGWFLQNGGCGYVLRPSIMRDEvsyfSANTKGIVP---G 718
Cdd:PLN02230  390 RIYPKGTRFNSSNYKPQIGWMSGAQMIAFNMQGYGRALWLMEGMFRANGGCGYVKKPDFLMDA----GPNGQDFYPkdnS 465

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  719 VSPLVLHIKIISGQ----NFPKpkgacAKGDVIDP---YVCVEIHGIPADCCEQRTKtVQQNSDNPIFDETFEFQVNLPE 791
Cdd:PLN02230  466 CPKKTLKVKVCMGDgwllDFKK-----THFDSYSPpdfFVRVGIAGAPVDEVMEKTK-IEYDTWTPIWNKEFIFPLAVPE 539

                         490       500       510
                  ....*....|....*....|....*....|....*....
gi 167900458  792 LTMVRFVILDDDY-IGDEFIGQYTIPFECLQPGYRHVPL 829
Cdd:PLN02230  540 LALLRVEVHEHDInEKDDFGGQTCLPVSEIRQGIHAVPL 578

PI-PLCc

cd00137

Catalytic domain of prokaryotic and eukaryotic phosphoinositide-specific phospholipase C; This ...

398-689

8.81e-46

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: 166.29 E-value: 8.81e-46

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  398 AQDMTQPLSHYYINASHNTYLIEDQF-----RGPADINGYVRALKMGCRSIELDVSDGPDNEPILCNRNNMaMHLSFRSV 472
Cdd:cd00137     1 HHPDTQPLAHYSIPGTHDTYLTAGQFtikqvWGLTQTEMYRQQLLSGCRCVDIRCWDGKPEEPIIYHGPTF-LDIFLKEV 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  473 LEVINKFAFVASEYPLILCLGNHCSLP--QQKVMAQQMKKVFGEkLYTEAPLSSESYLPSPEKLKNMIIVKGKKLPSesd 550
Cdd:cd00137    80 IEAIAQFLKKNPPETIIMSLKNEVDSMdsFQAKMAEYCRTIFGD-MLLTPPLKPTVPLPSLEDLRGKILLLNKKNGF--- 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  551 llEGEVTDEDEEAEMSRRMSGdyngeqkhiwlcrelsdlvsicksvqhrdfelsMKTQNYwEMCSFSETEASRIAN---- 626
Cdd:cd00137   156 --SGPTGSSNDTGFVSFEFST---------------------------------QKNRSY-NISSQDEYKAYDDEKvkli 199

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 167900458  627 EYPEDFVNYNKKFLSRVYPSAMRI---------DSSNLNPQDFWN---CGCQIVAMNFQTPGPMMDLHTGWFLQN 689
Cdd:cd00137   200 KATVQFVDYNKNQLSRNYPSGTSGgtawyyyamDSNNYMPQMFWNanpAGCGIVILDFQTMDLPMQQYMAVIEFN 274

PLN02223

phosphoinositide phospholipase C

368-829

5.02e-39

phosphoinositide phospholipase C

Pssm-ID: 165867 [Multi-domain] Cd Length: 537 Bit Score: 153.64 E-value: 5.02e-39

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  368 RQKGFLAIDGFTQYLLSPECDifDPEQKKVA-QDMTQPLSHYYINASHNTYLI-EDQFRGPADINGYVRALKMGCRSIEL 445
Cdd:PLN02223   76 RNLRCLELDHLNEFLFSTELN--PPIGDQVRhHDMHAPLSHYFIHTSLKSYFTgNNVFGKLYSIEPIIDALEQGVRVVEL 153

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  446 DVSdgPDNEPILCNRN--NMAMHLSFRSVLEVINKFAFVASE-YPLILCLGNHCSLPQQKVMAQQMKKVFGEKLYTEAPL 522
Cdd:PLN02223  154 DLL--PDGKDGICVRPkwNFEKPLELQECLDAIKEHAFTKCRsYPLIITFKDGLKPDLQSKATQMIDQTFGDMVYHEDPQ 231

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  523 SSESYLPSPEKLKNMIIVKgKKLPSE---SDLLEGEVTDEDEeAEMsRRMSGDYNGEQkhiwlcrelsdLVSIcKSVQHR 599
Cdd:PLN02223  232 HSLEEFPSPAELQNKILIS-RRPPKEllyAKADDGGVGVRNE-LEI-QEGPADKNYQS-----------LVGF-HAVEPR 296

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  600 DFELSMKTqnywemcsfseTEASRIANE--YPEDFVNYNKKFLSRVYPSAMRIDS-SNLNPQDFWNCGCQIVAMNFQTPG 676
Cdd:PLN02223  297 GMLQKALT-----------GKADDIQQPgwYERDIISFTQKKFLRTRPKKKNLLInAPYKPQRAWMHGAQLIALSRKDDK 365

                         330       340       350       360       370       380       390       400
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  677 PMMDLHTGWFLQNGGCGYVLRPSIMrdevsyFSANTKGIV-PGVSPLV---LHIKIISGQ----NFPKPKGACAKGDVid 748
Cdd:PLN02223  366 EKLWLMQGMFRANGGCGYVKKPDFL------LNAGPSGVFyPTENPVVvkiLKVKIYMGDgwivDFKKRIGRLSKPDL-- 437

                         410       420       430       440       450       460       470       480
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  749 pYVCVEIHGIPADCCEQRTkTVQQNSDNPIFDETFEFQVNLPELTMVRFVILDDDY-IGDEFIGQYTIPFECLQPGYRHV 827
Cdd:PLN02223  438 -YVRISIAGVPHDEKIMKT-TVKNNEWKPTWGEEFTFPLTYPDLALISFEVYDYEVsTADAFCGQTCLPVSELIEGIRAV 515


                  ..
gi 167900458  828 PL 829
Cdd:PLN02223  516 PL 517

PH_PLC_ELMO1

cd01248

Phospholipase C and Engulfment and cell motility protein 1 pleckstrin homology domain; The ...

116-223

4.83e-33

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: 123.59 E-value: 4.83e-33

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  116 MQAGCELKKVRPNSRIYNRFFTLDTDLQALRWEPSKKDLEKAKLDISAIKEIRLGKNTETFRNNGLADQICEDCAFSILH 195
Cdd:cd01248     1 LQQGTLLLKYREGSKPKERTFYLDPDGTRITWESSKKKSEKKSIDISDIKEIRPGKDTDGFKRKKKSNKPKEERCFSIIY 80

                          90       100
                  ....*....|....*....|....*...
gi 167900458  196 GENYESLDLVANSADVANIWVSGLRYLV 223
Cdd:cd01248    81 GSNNKTLDLVAPSEDEANLWVEGLRALL 108

EFh_PI-PLCeta

cd16205

EF-hand motif found in phosphoinositide phospholipase C eta (PI-PLC-eta); PI-PLC-eta isozymes ...

244-386

5.40e-31

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: 118.64 E-value: 5.40e-31

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  244 WLKTVFEAADVDGNGIMLEDTSVELIKQLNPTLKESKIRLKFKEIQKSKEKLTtrVTEEEFCEAFCELCTRPEVYFLLVQ 323
Cdd:cd16205     1 WLKQTFEEADKNGDGLLSIGEILQLMHKLNVNLPRRKVRQMFKEADTDDNQGT--LDFEEFCAFYKMMSTRRELYLLLLS 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 167900458  324 ISKNKEYLDANDLMLFLEAEQGVTHITEDMCLDIIRRYELSEDGRQKGFLAIDGFTQYLLSPE 386
Cdd:cd16205    79 YSNKKDYLTLEDLARFLEVEQKMTNVTLEYCLDIIEKFEPSEENKKNGLLGIDGFTNYMRSPA 141

PH_12

pfam16457

Pleckstrin homology domain;

111-224

1.66e-29

Pleckstrin homology domain;

Pssm-ID: 465123 [Multi-domain] Cd Length: 128 Bit Score: 113.89 E-value: 1.66e-29

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458   111 DCISFMQAGCELKKVRPNSR-IYNRFFTLDTDLQALRWE---------PSKKDLEkAKLDISAIKEIRLGKNTETFRNNG 180
Cdd:pfam16457    4 QRLNCLLEGAWFPKVRGRRRkKKYRFCRLSPNRKVLHYGdfeekptvdPSLESLP-EKIDLSDIKEVVTGKECPHVRESG 82

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 167900458   181 -LADQICEDCAFSILHGE-NYESLDLVANSADVANIWVSGLRYLVS 224
Cdd:pfam16457   83 kKSKKTSSTLAFSLIYGAdEYELLDFVAPSESVAAIWLDGLNMLLG 128

EFh_PI-PLC

cd15898

EF-hand motif found in eukaryotic phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4. ...

244-386

1.44e-26

Pssm-ID: 320029 [Multi-domain] Cd Length: 137 Bit Score: 105.83 E-value: 1.44e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  244 WLKTVFEAADVDGNGIMLEDTSVELIKQLNPTLKESKIRLKFKEIQKSKeklTTRVTEEEFCEAFCELCTRPEVYFLLVQ 323
Cdd:cd15898     1 WLRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVDTNG---DGTLTFDEFEELYKSLTERPELEPIFKK 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 167900458  324 ISK-NKEYLDANDLMLFLEAEQGVThITEDMCLDIIRRYELSEDGRQkgfLAIDGFTQYLLSPE 386
Cdd:cd15898    78 YAGtNRDYMTLEEFIRFLREEQGEN-VSEEECEELIEKYEPERENRQ---LSFEGFTNFLLSPE 137

EFh_PI-PLCdelta

cd16202

EF-hand motif found in phosphoinositide phospholipase C delta (PI-PLC-delta); PI-PLC-delta ...

244-386

2.99e-26

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: 105.39 E-value: 2.99e-26

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  244 WLKTVFEAADVDGNGIMLEDTSVELIKQLNPTLKESKIRLKFKEIQKSKEkltTRVTEEEFCEAFCELCTRPEVYFLLVQ 323
Cdd:cd16202     1 WLKDQFRKADKNGDGKLSFKECKKLLKKLNVKVDKDYAKKLFQEADTSGE---DVLDEEEFVQFYNRLTKRPEIEELFKK 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 167900458  324 ISKNKEYLDANDLMLFLEAEQGVTHITEDMCLDIIRRYELSEDGRQKGFLAIDGFTQYLLSPE 386
Cdd:cd16202    78 YSGDDEALTVEELRRFLQEEQKVKDVTLEWAEQLIETYEPSEDLKAQGLMSLDGFTLFLLSPD 140

EFh_PI-PLCeta2

cd16221

EF-hand motif found in phosphoinositide phospholipase C eta 2 (PI-PLC-eta2); PI-PLC-eta2, also ...

244-385

2.64e-24

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: 99.62 E-value: 2.64e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  244 WLKTVFEAADVDGNGIMLEDTSVELIKQLNPTLKESKIRLKFKEIQKSKEKLTtrVTEEEFCEAFCELCTRPEVYFLLVQ 323
Cdd:cd16221     1 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEADTDDNQGT--LGFEEFCAFYKMMSTRRDLYLLMLT 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 167900458  324 ISKNKEYLDANDLMLFLEAEQGVTHITEDMCLDIIRRYELSEDGRQKGFLAIDGFTQYLLSP 385
Cdd:cd16221    79 YSNHKDHLDTNDLQRFLEVEQKMAGVTREHCLEIISQFEPCSENKQNGALGIDGFTNYMRSP 140

EFh_PI-PLCeta1

cd16220

EF-hand motif found in phosphoinositide phospholipase C eta 1 (PI-PLC-eta1); PI-PLC-eta1, also ...

244-385

3.21e-24

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: 99.33 E-value: 3.21e-24

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  244 WLKTVFEAADVDGNGIMLEDTSVELIKQLNPTLKESKIRLKFKEIQKSKEKLTtrVTEEEFCEAFCELCTRPEVYFLLVQ 323
Cdd:cd16220     1 WVKQTFEEADKNGDGLLNIEEIYQLMHKLNVNLPRRKVRQMFQEADTDENQGT--LTFEEFCVFYKMMSLRRDLYLLLLS 78

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 167900458  324 ISKNKEYLDANDLMLFLEAEQGVTHITEDMCLDIIRRYELSEDGRQKGFLAIDGFTQYLLSP 385
Cdd:cd16220    79 YSDKKDHLTVEELAQFLKVEQKMNNVTTEYCLDIIKKFEVSEENKEQNVLGIEGFTNFMRSP 140

smart00239

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...

723-829

5.46e-24

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 97.17 E-value: 5.46e-24

                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458    723 VLHIKIISGQNFPKPKgacaKGDVIDPYVCVEIHGipADCCEQRTKTVQqNSDNPIFDETFEFQVNLPELTMVRFVILDD 802
Cdd:smart00239    1 TLTVKIISARNLPPKD----KGGKSDPYVKVSLDG--DPKEKKKTKVVK-NTLNPVWNETFEFEVPPPELAELEIEVYDK 73

                            90       100
                    ....*....|....*....|....*...
gi 167900458    803 DYIG-DEFIGQYTIPFECLQPGYRHVPL 829
Cdd:smart00239   74 DRFGrDDFIGQVTIPLSDLLLGGRHEKL 101

pfam00168

C2 domain;

723-826

5.08e-19

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 83.14 E-value: 5.08e-19

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458   723 VLHIKIISGQNFPKPKGacakGDVIDPYVCVEIHGipadcCEQRTKT-VQQNSDNPIFDETFEFQVNLPELTMVRFVILD 801
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDG----NGTSDPYVKVYLLD-----GKQKKKTkVVKNTLNPVWNETFTFSVPDPENAVLEIEVYD 72

                           90       100
                   ....*....|....*....|....*.
gi 167900458   802 DDYIG-DEFIGQYTIPFECLQPGYRH 826
Cdd:pfam00168   73 YDRFGrDDFIGEVRIPLSELDSGEGL 98

PH_PLC_delta

cd13363

Phospholipase C-delta (PLC-delta) pleckstrin homology (PH) domain; The PLC-delta (PLCdelta) ...

116-227

1.10e-17

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: 80.06 E-value: 1.10e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  116 MQAGCELKKVRPNSRIYNRFFTLDTDLQALrWEPSKKDLEKAK--LDISAIKEIRLGKNTETFRNngLADQICEDCAFSI 193
Cdd:cd13363     1 LLQGSPLLKVRSRSWKKERFYKLQEDCKTV-WHESKKTRSNSKqtFSIEDIESVREGHQSEGLRK--YAEAFPEDRCFSI 77

                          90       100       110
                  ....*....|....*....|....*....|....
gi 167900458  194 LHGENYESLDLVANSADVANIWVSGLRYLVSRSK 227
Cdd:cd13363    78 VFKGRRKNLDLIAPSEEEAQRWVRGLEKLIARLT 111

PH_PLC_plant-like

cd13365

Plant-like Phospholipase C (PLC) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) was the ...

111-224

1.74e-17

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

Pssm-ID: 270171 Cd Length: 115 Bit Score: 79.25 E-value: 1.74e-17

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  111 DCISFMQAGCELKKVRPNSRIYNRFFTLDTDLQALRWEPSKKDLEKaKLDISAIKEIRLGKNTETFRNNGLADqiCEDCA 190
Cdd:cd13365     5 EAITQLKIGSYLLKYGRRGKPHFRYFWLSPDELTLYWSSPKKGSEK-RVRLSSVSRIIPGQRTVVFKRPPPPG--LEEHS 81

                          90       100       110
                  ....*....|....*....|....*....|....
gi 167900458  191 FSILHGENYESLDLVANSADVANIWVSGLRYLVS 224
Cdd:cd13365    82 FSIIYADGERSLDLTCKDRQEFDTWFTGLRYLLS 115

cd00030

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...

724-816

3.29e-16

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: 75.18 E-value: 3.29e-16

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  724 LHIKIISGQNFPKPKgacaKGDVIDPYVCVEIHGIpadcCEQRTKTVQqNSDNPIFDETFEFQVNLPELTMVRFVILDDD 803
Cdd:cd00030     1 LRVTVIEARNLPAKD----LNGKSDPYVKVSLGGK----QKFKTKVVK-NTLNPVWNETFEFPVLDPESDTLTVEVWDKD 71

                          90
                  ....*....|....
gi 167900458  804 YIG-DEFIGQYTIP 816
Cdd:cd00030    72 RFSkDDFLGEVEIP 85

EF-hand_like

pfam09279

Phosphoinositide-specific phospholipase C, efhand-like; Members of this family are ...

311-391

3.86e-12

Pssm-ID: 401279 [Multi-domain] Cd Length: 85 Bit Score: 63.03 E-value: 3.86e-12

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458   311 LCTRPEVYFLLVQISKNKEYLDANDLMLFLEAEQGVTHITEDMCLDIIRRYELSEDGRQKGFLAIDGFTQYLLSPECDIF 390
Cdd:pfam09279    5 LTQREEIDEIFQEYSGDGQKLSLDELVDFLREEQREEDASPALALSLIERYEPSETAKKQHAMTKDGFLMYLCSPDGSIF 84


                   .
gi 167900458   391 D 391
Cdd:pfam09279   85 N 85

PH_PLC_gamma

cd13362

Phospholipase C-gamma (PLC-gamma) pleckstrin homology (PH) domain; PLC-gamma (PLCgamma) is ...

116-224

8.50e-12

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: 63.06 E-value: 8.50e-12

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  116 MQAGCELKKVRPNSRIYNRFFTLDTDLQALRWEPSKKDLEKAKLDISAIKEIRLGKNTETF-RNNGLADQICEDCAFSIL 194
Cdd:cd13362     1 LERGTVMTKFYQKKRPERRTFQVKLETRQVVWSRGGGKRAEGAVDIREIKEIRPGKNSKDFeRWPDEAKKLDPSCCFVIL 80

                          90       100       110
                  ....*....|....*....|....*....|..
gi 167900458  195 HGENY--ESLDLVANSADVANIWVSGLRYLVS 224
Cdd:cd13362    81 YGTEFrlKTLSVAATSEEECDMWIKGLRYLVE 112

EFh_PI-PLCdelta3

cd16218

EF-hand motif found in phosphoinositide phospholipase C delta 3 (PI-PLC-delta3); PI-PLC-delta3, ...

244-386

1.41e-10

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: 60.14 E-value: 1.41e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  244 WLKTVFEAADVDGNGIMLEDTSVELIKQLNPTLKESKIRLKFKEIQKSKeklTTRVTEEEFCEAFCELCTRPEVYFLLVQ 323
Cdd:cd16218     1 WIHEYLRRADLNKDGKMSFEEIKDLLQMINIDLNEQYAYQLFKECDRSN---DDRLEEHEIEEFCRRLMQRPELEEIFHQ 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 167900458  324 ISKNKEYLDANDLMLFLEaEQGvthitEDMCL----DIIRRYELSEDGRQKGFLAIDGFTQYLLSPE 386
Cdd:cd16218    78 YSGEDCVLSAEELREFLK-DQG-----EDASLvhakELIQTYELNEKAKQHQLMTLDGFTMYMLSKD 138

EFh_PI-PLCbeta

cd16200

EF-hand motif found in metazoan phosphoinositide-specific phospholipase C (PI-PLC)-beta ...

311-386

2.98e-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: 59.57 E-value: 2.98e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  311 LCTRPEVYFLLVQIS-KNKEYLDANDLMLFLEAEQG--------VTHITEDMCLDIIRRYELSEDGRQKGFLAIDGFTQY 381
Cdd:cd16200    69 LCPRPDIDEIFKELGgKRKPYLTLEQLVDFLNEEQRdprlneilFPFHTKEQAKKLIDKYEPNEKNKKKGQLTLEGFLRY 148


                  ....*
gi 167900458  382 LLSPE 386
Cdd:cd16200   149 LMSDE 153

EFh_PI-PLCdelta4

cd16219

EF-hand motif found in phosphoinositide phospholipase C delta 4 (PI-PLC-delta4); PI-PLC-delta4, ...

244-386

4.35e-10

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: 59.09 E-value: 4.35e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  244 WLKTVFEAADVDGNGIMLEDTSVELIKQLNPTLKESKIRLKFKEIQKSKeklTTRVTEEEFCEAFCELCTRPEVYFLLVQ 323
Cdd:cd16219     1 WIRDWFQKADKNKDGRMNFKEVRDLLKMMNVDMNEEHALRLFQMADKSE---SGTLEGEEFVLFYKALTQREDVLKIFQD 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 167900458  324 ISKNKEYLDANDLMLFLEAEQGVTHITEDMCLDIIRRYELSEDGRQKGFLAIDGFTQYLLSPE 386
Cdd:cd16219    78 FSADGQKLTLLEFVDFLQQEQLERENTEELAMELIDRYEPSDTAKKLHALSIDGFLMYLCSPE 140

C2B_Munc13-like

cd04009

C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...

723-838

6.00e-10

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: 58.40 E-value: 6.00e-10

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  723 VLHIKIISGQNF--PKPKGACakgdviDPYVCVEIhgIP----ADCCEQRTKtVQQNSDNPIFDETFEFQVN----LPEL 792
Cdd:cd04009    17 SLRVEILNARNLlpLDSNGSS------DPFVKVEL--LPrhlfPDVPTPKTQ-VKKKTLFPLFDESFEFNVPpeqcSVEG 87

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 167900458  793 TMVRFVILDDDYIG-DEFIGQYTIPFECLqPGYRHVPLRSFVGDIME 838
Cdd:cd04009    88 ALLLFTVKDYDLLGsNDFEGEAFLPLNDI-PGVEDTSSAQGFGPLPQ 133

C2_cPLA2

cd04036

C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is ...

723-823

1.58e-09

C2 domain present in cytosolic PhosphoLipase A2 (cPLA2); A single copy of the C2 domain is present in cPLA2 which releases arachidonic acid from membranes initiating the biosynthesis of potent inflammatory mediators such as prostaglandins, leukotrienes, and platelet-activating factor. 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 of this cd have a type-II topology.

Pssm-ID: 176001 [Multi-domain] Cd Length: 119 Bit Score: 56.50 E-value: 1.58e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  723 VLHIKIISGQNFPKpkgacakGDVI---DPYVcvEIHgIP-ADCCEQRTKTVQqNSDNPIFDETFEFQV-----NLPELT 793
Cdd:cd04036     1 LLTVRVLRATNITK-------GDLLstpDCYV--ELW-LPtASDEKKRTKTIK-NSINPVWNETFEFRIqsqvkNVLELT 69

                          90       100       110
                  ....*....|....*....|....*....|
gi 167900458  794 MvrfviLDDDYIGDEFIGQYTIPFECLQPG 823
Cdd:cd04036    70 V-----MDEDYVMDDHLGTVLFDVSKLKLG 94

PH_PLC_fungal

cd13360

Fungal Phospholipase C (PLC) pleckstrin homology (PH) domain; Fungal PLC have mostly been ...

116-223

2.83e-08

Fungal Phospholipase C (PLC) pleckstrin homology (PH) domain; Fungal PLC have mostly been characterized in the yeast Saccharomyces cerevisiae via deletion studies which resulted in a pleiotropic phenotype, with defects in growth, carbon source utilization, and sensitivity to osmotic stress and high temperature. Unlike Saccharomyces several other fungi including Neurospora crassa, Cryphonectria parasitica , and Magnaporthe oryzae (Mo) have several PLC proteins, some of which lack a PH domain, with varied functions. MoPLC1-mediated regulation of Ca2+ level is important for conidiogenesis and appressorium formation while both MoPLC2 and MoPLC3 are required for asexual reproduction, cell wall integrity, appressorium development, and pathogenicity. The fungal PLCs in this hierarchy contain an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves, 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). 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: 241514 Cd Length: 118 Bit Score: 52.95 E-value: 2.83e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  116 MQAGCELKKVRPNSRIyNRFFTLDTDLQALRWEPSKKdleKAKLDISAIKEIRLGKNTETFRNN-GLADQIcEDCAFSIL 194
Cdd:cd13360     1 LRQGTPLLKVTKKKKK-RILFKLDPESGKITWDSKKP---SKSLYIDDIKEIRTGEDARNYREEfGISEEF-EDRWITII 75

                          90       100       110
                  ....*....|....*....|....*....|...
gi 167900458  195 ----HGENYESLDLVANSADVANIWVSGLRYLV 223
Cdd:cd13360    76 yfvpKKNKLKTLHLIADTEEDFKLWTTTLEGLV 108

C2A_Rabphilin_Doc2

cd04035

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...

724-822

3.93e-08

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: 52.67 E-value: 3.93e-08

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  724 LHIKIISGQNFPkpkgACAKGDVIDPYVcvEIHGIP--ADCCEQRTKTVQqNSDNPIFDETFEFQVNLPE---LTMVRFV 798
Cdd:cd04035    17 LHCTIIRAKGLK----AMDANGLSDPYV--KLNLLPgaSKATKLRTKTVH-KTRNPEFNETLTYYGITEEdiqRKTLRLL 89

                          90       100
                  ....*....|....*....|....
gi 167900458  799 ILDDDYIGDEFIGQYTIPFECLQP 822
Cdd:cd04035    90 VLDEDRFGNDFLGETRIPLKKLKP 113

C2_C21orf25-like

cd08678

C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The ...

724-831

1.04e-07

C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The members in this cd are named after the Human C21orf25 which contains a single C2 domain. Several other members contain a C1 domain downstream of the C2 domain. No other information on this protein is currently known. 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: 176060 [Multi-domain] Cd Length: 126 Bit Score: 51.60 E-value: 1.04e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  724 LHIKIIsgqnfpKPKGACAKGDVIDPYVCVEIHGIPadcceQRTKT-VQQNSDNPIFDETFEFQVNlPELTMVRFVILDD 802
Cdd:cd08678     1 LLVKNI------KANGLSEAAGSSNPYCVLEMDEPP-----QKYQSsTQKNTSNPFWDEHFLFELS-PNSKELLFEVYDN 68

                          90       100       110
                  ....*....|....*....|....*....|...
gi 167900458  803 DYIGDE-FIGQYTIPFECL--QPGYRHV-PLRS 831
Cdd:cd08678    69 GKKSDSkFLGLAIVPFDELrkNPSGRQIfPLQG 101

EFh_PI-PLCdelta1

cd16217

EF-hand motif found in phosphoinositide phospholipase C delta 1 (PI-PLC-delta1); PI-PLC-delta1, ...

244-386

1.23e-07

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: 52.05 E-value: 1.23e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  244 WLKTVFEAADVDGNGIMLEDTSVELIKQLNPTLKESKIRLKFKEIQKSKeklTTRVTEEEFCEAFCELCTRPEVYFLLVQ 323
Cdd:cd16217     1 WIHSCLRKADKNKDNKMSFKELKDFLKEINIEVDDDYAEKLFKECDKSK---SGFLEGEEIEEFYKLLTKREEIDVIFGE 77

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 167900458  324 ISKNKEYLDANDLMLFLEAEQGvTHITEDMCLDIIRRYELSEDGRQKGFLAIDGFTQYLLSPE 386
Cdd:cd16217    78 YAKSDGTMSRNNLLNFLQEEQR-EEVAPAYALSLIEKYEPDETAKAQRQMTKDGFLMYLLSPE 139

PI-PLCc_GDPD_SF

cd08555

Catalytic domain of phosphoinositide-specific phospholipase C-like phosphodiesterases ...

411-516

1.28e-07

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: 52.82 E-value: 1.28e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  411 NASHNTYLIEDQfrgPADINGYVRALKMGCRSIELDVSDGPDNEPIL-----CNRNNMAMH-LSFRSVLEVINKFAFvAS 484
Cdd:cd08555     1 VLSHRGYSQNGQ---ENTLEAFYRALDAGARGLELDVRLTKDGELVVyhgptLDRTTAGILpPTLEEVLELIADYLK-NP 76

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 167900458  485 EYPLILCLGNHCS----LPQQKVMAQQMKKVFGEKL 516
Cdd:cd08555    77 DYTIILSLEIKQDspeyDEFLAKVLKELRVYFDYDL 112

C2B_Synaptotagmin

cd00276

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...

724-826

1.74e-07

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: 51.43 E-value: 1.74e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  724 LHIKIISGQNFPKPKGacakGDVIDPYVCVEIHgipadCCEQRTK----TVQQNSDNPIFDETFEFQVN---LPELTMVr 796
Cdd:cd00276    16 LTVVVLKARNLPPSDG----KGLSDPYVKVSLL-----QGGKKLKkkktSVKKGTLNPVFNEAFSFDVPaeqLEEVSLV- 85

                          90       100       110
                  ....*....|....*....|....*....|.
gi 167900458  797 FVILDDDYIG-DEFIGQYTIPFECLQPGYRH 826
Cdd:cd00276    86 ITVVDKDSVGrNEVIGQVVLGPDSGGEELEH 116

EFh_PI-PLC21

cd16213

EF-hand motif found in phosphoinositide phospholipase PLC21 and similar proteins; The family ...

311-386

7.46e-07

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: 49.99 E-value: 7.46e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  311 LCTRPEVYFLLVQIS-KNKEYLDANDLMLFLEAEQ---GVTHI-----TEDMCLDIIRRYELSEDGRQKGFLAIDGFTQY 381
Cdd:cd16213    70 LTGRQEVEKIFDELGaKKKPYLTTEQFVDFLNKTQrdpRLNEIlypyaNPKRARDLINQYEPNKSFAKKGHLSVEGFLRY 149


                  ....*
gi 167900458  382 LLSPE 386
Cdd:cd16213   150 LMSED 154

C2A_Synaptotagmin-15-17

cd08390

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...

723-820

1.36e-06

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176036 [Multi-domain] Cd Length: 123 Bit Score: 48.41 E-value: 1.36e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  723 VLHIKIISGQNFPKPKGACAkgdVIDPYVcvEIHGIPADCCEQRTKtVQQNSDNPIFDETFEFQVNLPELT--MVRFVIL 800
Cdd:cd08390    15 QLTVSLIKARNLPPRTKDVA---HCDPFV--KVCLLPDERRSLQSK-VKRKTQNPNFDETFVFQVSFKELQrrTLRLSVY 88

                          90       100
                  ....*....|....*....|....*
gi 167900458  801 DddyiGDEF-----IGQYTIPFECL 820
Cdd:cd08390    89 D----VDRFsrhciIGHVLFPLKDL 109

C2B_RasA3

cd04010

C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of ...

724-821

2.56e-06

C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of GTPase activating protein 1 (GAP1), a Ras-specific GAP, 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. RasA3 contains an N-terminal C2 domain, 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: 175977 [Multi-domain] Cd Length: 148 Bit Score: 48.16 E-value: 2.56e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  724 LHIKIISGQNFPKPKGACakgdviDPYVCVEIHGIPADCCEQRTKtVQQNSDNPIFDETFEFQVNLPELTMVRFVILDDD 803
Cdd:cd04010     2 LSVRVIECSDLALKNGTC------DPYASVTLIYSNKKQDTKRTK-VKKKTNNPQFDEAFYFDVTIDSSPEKKQFEMPEE 74

                          90       100       110
                  ....*....|....*....|....*....|....
gi 167900458  804 YI----------------GDEFIGQYTIPFECLQ 821
Cdd:cd04010    75 DAeklelrvdlwhasmggGDVFLGEVRIPLRGLD 108

C2B_RasGAP

cd08675

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...

724-821

8.69e-06

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress 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. The proteins here all contain two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like 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-I topology.

Pssm-ID: 176057 [Multi-domain] Cd Length: 137 Bit Score: 46.60 E-value: 8.69e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  724 LHIKIISGQN-FPKPKGACakgdviDPYVCVEIHGiPADCCEQRTKtVQQNSDNPIFDETFEFQVNLP------------ 790
Cdd:cd08675     1 LSVRVLECRDlALKSNGTC------DPFARVTLNY-SSKTDTKRTK-VKKKTNNPRFDEAFYFELTIGfsyekksfkvee 72

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 167900458  791 ---ELTMVRFVILDDDYIG-DEFIGQYTIPFECLQ 821
Cdd:cd08675    73 edlEKSELRVELWHASMVSgDDFLGEVRIPLQGLQ 107

C2_putative_Elicitor-responsive_gene

cd04049

C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive ...

722-830

9.37e-06

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: 46.17 E-value: 9.37e-06

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  722 LVLHIKIISGQNFPKPkgacakgdvIDPYVcvEIHgipadcC---EQRTKTVQQNSDNPIFDETFEFQVNLPE---LTMV 795
Cdd:cd04049     6 LLISAKGLQDTDFLGK---------IDPYV--IIQ------CrtqERKSKVAKGDGRNPEWNEKFKFTVEYPGwggDTKL 68

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 167900458  796 RFVILDDDYI-GDEFIGQYTIPFECL-----QPGYRHVPLR 830
Cdd:cd04049    69 ILRIMDKDNFsDDDFIGEATIHLKGLfeegvEPGTAELVPA 109

C2A_Tricalbin-like

cd04044

C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...

723-789

1.08e-05

C2 domain first repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.

Pssm-ID: 176009 [Multi-domain] Cd Length: 124 Bit Score: 46.01 E-value: 1.08e-05

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 167900458  723 VLHIKIISGQNFpkpKGACAKGDVIDPYVCVEIHGIPADcceQRTKTVQqNSDNPIFDETFEFQVNL 789
Cdd:cd04044     3 VLAVTIKSARGL---KGSDIIGGTVDPYVTFSISNRREL---ARTKVKK-DTSNPVWNETKYILVNS 62

EFh_PI-PLCzeta

cd16204

EF-hand motif found in phosphoinositide phospholipase C zeta 1 (PI-PLC-zeta1); PI-PLC-zeta1, ...

263-386

1.12e-05

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: 46.34 E-value: 1.12e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  263 DTSVELIKQLNPTLKESKIRLKFKEIQKSKEKlttRVTEEEFCEAFCELCTRPEVYFLLVQISKNKEYLDANDLMLFLEA 342
Cdd:cd16204    22 ESTLKLLEKLDIPFDYIHVKYIFKKNDSFKAG---NITIEDFRAIYRAIAHRCEIHEIFNTYSENRKILSAPNLVGFLKK 98

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 167900458  343 EQGVTHITEDMCLDIIRRYELSEDGRQKGFLAIDGFTQYLLSPE 386
Cdd:cd16204    99 EQFQDEADETIASELIAKYEPIEEVRKRKQMSFEGFIRYMTSED 142

C2B_Ferlin

cd04011

C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...

725-813

1.65e-05

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: 44.87 E-value: 1.65e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  725 HIKIISGQnfpkpkgaCAKGDVIDPYVCVEihgipadCCEQRTKTVQQNSDN-PIFDETFEFQVNLPELTM----VRFVI 799
Cdd:cd04011     7 RVRVIEAR--------QLVGGNIDPVVKVE-------VGGQKKYTSVKKGTNcPFYNEYFFFNFHESPDELfdkiIKISV 71

                          90
                  ....*....|....*
gi 167900458  800 LDDDYIG-DEFIGQY 813
Cdd:cd04011    72 YDSRSLRsDTLIGSF 86

C2_NEDD4_NEDD4L

cd04033

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated ...

723-816

1.93e-05

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42); Nedd4 and Nedd4-2 are two of the nine members of the Human Nedd4 family. All vertebrates appear to have both Nedd4 and Nedd4-2 genes. They are thought to participate in the regulation of epithelial Na+ channel (ENaC) activity. They also have identical specificity for ubiquitin conjugating enzymes (E2). Nedd4 and Nedd4-2 are composed of a C2 domain, 2-4 WW domains, and a ubiquitin ligase Hect domain. Their WW domains can bind PPxY (PY) or LPSY motifs, and in vitro studies suggest that WW3 and WW4 of both proteins bind PY motifs in the key substrates, with WW3 generally exhibiting higher affinity. Most Nedd4 family members, especially Nedd4-2, also have multiple splice variants, which might play different roles in regulating their substrates. 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: 175999 [Multi-domain] Cd Length: 133 Bit Score: 45.42 E-value: 1.93e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  723 VLHIKIISGQNFPKPK--GACakgdviDPYVCVEIHGIPAD--CCEQRTKTVQQnSDNPIFDETFEFQVNLPELTMVrFV 798
Cdd:cd04033     1 ILRVKVLAGIDLAKKDifGAS------DPYVKISLYDPDGNgeIDSVQTKTIKK-TLNPKWNEEFFFRVNPREHRLL-FE 72

                          90
                  ....*....|....*....
gi 167900458  799 ILDDDYIG-DEFIGQYTIP 816
Cdd:cd04033    73 VFDENRLTrDDFLGQVEVP 91

C2B_Tricalbin-like

cd04052

C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...

742-831

3.29e-05

C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 176017 [Multi-domain] Cd Length: 111 Bit Score: 44.13 E-value: 3.29e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  742 AKGDVIDPYVCV-----EIHgipadcceqRTKTVQQNSdNPIFDETFEFQVNLPELTMVRFVILDDDYIGDEFIGQYTIP 816
Cdd:cd04052     8 SKTGLLSPYAELylngkLVY---------TTRVKKKTN-NPSWNASTEFLVTDRRKSRVTVVVKDDRDRHDPVLGSVSIS 77

                          90
                  ....*....|....*....
gi 167900458  817 ----FECLQPGYRHVPLRS 831
Cdd:cd04052    78 lndlIDATSVGQQWFPLSG 96

C2A_Synaptotagmin-8

cd08387

C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...

723-818

4.52e-05

C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. 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: 176033 [Multi-domain] Cd Length: 124 Bit Score: 43.93 E-value: 4.52e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  723 VLHIKIISGQNFpKPK---GACakgdviDPYVCVEIhgIPADCCEQRTKtVQQNSDNPIFDETFEFQV---NLPELTmVR 796
Cdd:cd08387    17 ILNVKLIQARNL-QPRdfsGTA------DPYCKVRL--LPDRSNTKQSK-IHKKTLNPEFDESFVFEVppqELPKRT-LE 85

                          90       100
                  ....*....|....*....|...
gi 167900458  797 FVILD-DDYIGDEFIGQYTIPFE 818
Cdd:cd08387    86 VLLYDfDQFSRDECIGVVELPLA 108

PH_14

pfam17787

PH domain; This entry corresponds to the PH domain found at the N-terminus of phospholipase C ...

114-224

5.30e-05

PH domain; This entry corresponds to the PH domain found at the N-terminus of phospholipase C enzymes.

Pssm-ID: 465506 Cd Length: 131 Bit Score: 43.91 E-value: 5.30e-05

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458   114 SFMQAGCELKKVRPNSRIY--NRFFTLDTDLQALRWEPSKKDLEKakLDISAIKEIRLGKNTET-----FRN----NGLA 182
Cdd:pfam17787    4 EKLQKGELFIKWDEESTVAepNVLLKVDPKGFFLYWKSQGKEGEV--LEITSIRDTRLGKFAKIpkdpkLREvlsmGGSD 81

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 167900458   183 DQIcEDCAFSILHGENYESLD---LVANSADVANIWVSGLRYLVS 224
Cdd:pfam17787   82 NSL-EDKTLTVVSGTDMVNINfhnFVASNSEVAKNWAEGLRALAH 125

C2E_Ferlin

cd04037

C2 domain fifth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...

726-818

6.28e-05

C2 domain fifth 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 fifth C2 repeat, C2E, and has a type-II topology.

Pssm-ID: 176002 [Multi-domain] Cd Length: 124 Bit Score: 43.69 E-value: 6.28e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  726 IKIISGQNFPK--PKGACakgdviDPYVCVEI--HGIpadccEQRTKTVQQNSdNPIFDETFEFQVNLPELTMVRFVILD 801
Cdd:cd04037     4 VYVVRARNLQPkdPNGKS------DPYLKIKLgkKKI-----NDRDNYIPNTL-NPVFGKMFELEATLPGNSILKISVMD 71

                          90
                  ....*....|....*...
gi 167900458  802 DDYIG-DEFIGQYTIPFE 818
Cdd:cd04037    72 YDLLGsDDLIGETVIDLE 89

C2A_Ferlin

cd08373

C2 domain first repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...

722-822

7.84e-05

C2 domain first 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 first C2 repeat, C2A, and has a type-II topology.

Pssm-ID: 176019 [Multi-domain] Cd Length: 127 Bit Score: 43.40 E-value: 7.84e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  722 LVLHIKIISGQnfpKPKGacakgdviDPYVCVEIHGIPadcceQRTKTVQqNSDNPIFDETFEFQV-NLPELTMVRFVIL 800
Cdd:cd08373     1 LVVSLKNLPGL---KGKG--------DRIAKVTFRGVK-----KKTRVLE-NELNPVWNETFEWPLaGSPDPDESLEIVV 63

                          90       100
                  ....*....|....*....|....
gi 167900458  801 DDDY-IG-DEFIGQYTIPFECLQP 822
Cdd:cd08373    64 KDYEkVGrNRLIGSATVSLQDLVS 87

PH_ELMO1_CED-12

cd13359

Engulfment and cell motility protein 1 pleckstrin homology (PH) domain; DOCK2 (Dedicator of ...

148-222

1.05e-04

Engulfment and cell motility protein 1 pleckstrin homology (PH) domain; DOCK2 (Dedicator of cytokinesis 2), a hematopoietic cell-specific, atypical GEF, controls lymphocyte migration through Rac activation. A DOCK2-ELMO1 complex s necessary for DOCK2-mediated Rac signaling. DOCK2 contains a SH3 domain at its N-terminus, followed by a lipid binding DHR1 domain, and a Rac-binding DHR2 domain at its C-terminus. ELMO1, a mammalian homolog of C. elegans CED-12, contains the N-terminal RhoG-binding region, the ELMO domain, the PH domain, and the C-terminal sequence with three PxxP motifs. The C-terminal region of ELMO1, including the Pro-rich sequence, binds the SH3-containing region of DOCK2 forming a intermolecular five-helix bundle along with the PH domain of ELMO1. Autoinhibition of ELMO1 and DOCK2 is accomplished by the interactions of the EID and EAD domains and SH3 and DHR2 domains, respectively. The interaction of DOCK2 and ELMO1 mutually relieve their autoinhibition and results in the activation of Rac1. The PH domain of ELMO1 does not bind phosphoinositides due to the absence of key binding residues. It more closely resembles the FERM domain rather than other PH domains. 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: 270166 [Multi-domain] Cd Length: 126 Bit Score: 43.07 E-value: 1.05e-04

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 167900458  148 EPSKKDLEKAKLDISAIKEIRLGKN----TETFRNNGLADqicedCAFSILHGENyESLDLVANSADVANIWVSGLRYL 222
Cdd:cd13359    51 QPAPLEELPEKLPVADIKALVTGKDcphmKELKKNKSVAS-----LAFSILYDSD-ESLDFVAPNETVFDIWTDGLNAL 123

COG5038

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];

724-823

1.14e-04

Ca2+-dependent lipid-binding protein, contains C2 domain [General function prediction only];

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 46.29 E-value: 1.14e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  724 LHIKIISGQNFPkpkgACAKGDVIDPYVCVEIHGIPAdcceQRTKTVQQNSdNPIFDETFEFQVNLPELTMVRFVILDDD 803
Cdd:COG5038  1042 LTIMLRSGENLP----SSDENGYSDPFVKLFLNEKSV----YKTKVVKKTL-NPVWNEEFTIEVLNRVKDVLTINVNDWD 1112

                          90       100
                  ....*....|....*....|.
gi 167900458  804 YIG-DEFIGQYTIPFECLQPG 823
Cdd:COG5038  1113 SGEkNDLLGTAEIDLSKLEPG 1133

EFh_PI-PLCbeta4

cd16211

EF-hand motif found in phosphoinositide phospholipase C beta 4 (PI-PLC-beta4); PI-PLC-beta4, ...

311-386

1.59e-04

EF-hand motif found in phosphoinositide phospholipase C beta 4 (PI-PLC-beta4); PI-PLC-beta4, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4, or phospholipase C-beta-4 (PLC-beta4), is expressed in high concentrations in cerebellar Purkinje and granule cells, the median geniculate body, and the lateral geniculate nucleus. It may play a critical role in linking anxiety behaviors and theta rhythm heterogeneity. PI-PLC-beta4 is activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It contributes to generate cell-specific Ca2+ signals evoked by G protein-coupled receptor stimulation. PI-PLC-beta4 functions as a downstream signaling molecule of type 1 metabotropic glutamate receptors (mGluR1s). The thalamic mGluR1-PI-PLC-beta4 cascade is essential for formalin-induced inflammatory pain by regulating the response of ventral posterolateral thalamic nucleus (VPL) neurons. Moreover, PI-PLC-beta4 is essential for long-term depression (LTD) in the rostral cerebellum, which may be required for the acquisition of the conditioned eyeblink response. Besides, PI-PLC-beta4 may play an important role in maintenance of the status epilepticus. The mutations of PI-PLC-beta4 has been identified as the major cause of autosomal dominant auriculocondylar syndrome (ACS). PI-PLC-beta4 contains a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. Besides, it has a unique C-terminal coiled-coil (CT) domain necessary for homodimerization. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence.

Pssm-ID: 320041 Cd Length: 153 Bit Score: 43.18 E-value: 1.59e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  311 LCTRPEVYFLLVQISKN-KEYLDANDLMLFLEAEQGVTHITEDM--------CLDIIRRYELSEDGRQKGFLAIDGFTQY 381
Cdd:cd16211    69 ICPRTDIEELFKKINGDkKDYLTVDQLISFLNEHQRDPRLNEILfpfydrkrVMQIIETYEVDEEFKKKEQLSSDGFCRY 148


                  ....*
gi 167900458  382 LLSPE 386
Cdd:cd16211   149 LMSDE 153

C2B_Synaptotagmin-7

cd08405

C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...

724-816

1.80e-04

C2 domain second 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 second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176050 [Multi-domain] Cd Length: 136 Bit Score: 42.79 E-value: 1.80e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  724 LHIKIISGQNFpKPKGACAKGDvidPYVCVEIHgIPADCCEQRTKTVQQNSDNPIFDETFEFQVNLPELTMVRFVI--LD 801
Cdd:cd08405    17 ITVNIIKARNL-KAMDINGTSD---PYVKVWLM-YKDKRVEKKKTVIKKRTLNPVFNESFIFNIPLERLRETTLIItvMD 91

                          90
                  ....*....|....*.
gi 167900458  802 DDYIG-DEFIGQYTIP 816
Cdd:cd08405    92 KDRLSrNDLIGKIYLG 107

C2A_Synaptotagmin-like

cd04024

C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...

722-818

2.01e-04

C2 domain first repeat present in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. 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: 175990 [Multi-domain] Cd Length: 128 Bit Score: 42.41 E-value: 2.01e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  722 LVLHIKIISGQNF-PKPKGACAKGDvidPYVCVeihgipaDCCEQRTKT-VQQNSDNPIFDETFEFQVNLPELTMVRFVI 799
Cdd:cd04024     1 GVLRVHVVEAKDLaAKDRSGKGKSD---PYAIL-------SVGAQRFKTqTIPNTLNPKWNYWCEFPIFSAQNQLLKLIL 70

                          90       100
                  ....*....|....*....|
gi 167900458  800 LD-DDYIGDEFIGQYTIPFE 818
Cdd:cd04024    71 WDkDRFAGKDYLGEFDIALE 90

C2C_KIAA1228

cd04030

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins ...

705-792

2.84e-04

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. 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: 175996 [Multi-domain] Cd Length: 127 Bit Score: 41.87 E-value: 2.84e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  705 VSYFSANTKGIVpgvsplVLHikiiSGQNFPkpkgACAKGDVIDPYVcvEIHGIPADCCEQRTKT-VQQNSDNPIFDETF 783
Cdd:cd04030     9 IRYSSQRQKLIV------TVH----KCRNLP----PCDSSDIPDPYV--RLYLLPDKSKSTRRKTsVKKDNLNPVFDETF 72


                  ....*....
gi 167900458  784 EFQVNLPEL 792
Cdd:cd04030    73 EFPVSLEEL 81

C2_PKC_alpha_gamma

cd04026

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...

724-788

2.92e-04

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: 41.86 E-value: 2.92e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 167900458  724 LHIKIISGQNFP--KPKGacakgdVIDPYVCVEIHGIPADCCEQRTKTVQQNSdNPIFDETFEFQVN 788
Cdd:cd04026    15 LTVEVREAKNLIpmDPNG------LSDPYVKLKLIPDPKNETKQKTKTIKKTL-NPVWNETFTFDLK 74

C2A_C2C_Synaptotagmin_like

cd08391

C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...

723-816

3.38e-04

C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. 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 either the first or third repeat in Synaptotagmin-like proteins with a type-I topology.

Pssm-ID: 176037 [Multi-domain] Cd Length: 121 Bit Score: 41.51 E-value: 3.38e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  723 VLHIKIISGQN----------FPKPKGacakgdviDPYVCVEIHGIpadccEQRTKTVQQNSdNPIFDETFEFQVNLPEL 792
Cdd:cd08391     2 VLRIHVIEAQDlvakdkfvggLVKGKS--------DPYVIVRVGAQ-----TFKSKVIKENL-NPKWNEVYEAVVDEVPG 67

                          90       100
                  ....*....|....*....|....
gi 167900458  793 TMVRFVILDDDYIGDEFIGQYTIP 816
Cdd:cd08391    68 QELEIELFDEDPDKDDFLGRLSID 91

PH_PLC_beta

cd13361

Phospholipase C-beta (PLC-beta) pleckstrin homology (PH) domain; PLC-beta (PLCbeta) is ...

145-224

3.73e-04

Phospholipase C-beta (PLC-beta) pleckstrin homology (PH) domain; PLC-beta (PLCbeta) is regulated by heterotrimeric G protein-coupled receptors through their C2 domain and long C-terminal extension which forms an autoinhibitory helix. There are four isoforms: PLC-beta1-4. The PH domain of PLC-beta2 and PLC-beta3 plays a dual role, much like PLC-delta1, by binding to the plasma membrane, as well as the interaction site for the catalytic activator. However, PLC-beta binds to the lipid surface independent of PIP2. PLC-beta1 seems to play unspecified roles in cellular proliferation and differentiation. PLC-beta consists of an N-terminal PH domain, a EF hand domain, a catalytic domain split into X and Y halves, a C2 domain and a C-terminal PDZ. Members of the Rho GTPase family (e.g., Rac1, Rac2, Rac3, and cdc42) have been implicated in their activation by binding to an alternate site on the N-terminal PH domain. A basic amino acid region within the enzyme's long C-terminal tail appears to function as a Nuclear Localization Signal for import into 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.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: 270167 Cd Length: 127 Bit Score: 41.40 E-value: 3.73e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  145 LRWEPSKKDLEKakLDISAIKEIRLGKNT-------ETFRNNGLADQICEDCAFSILHGENYESLD---LVANSADVANI 214
Cdd:cd13361    31 LYWKSEGKETEV--LDLSLIRDVRTGKYPkdpkdlkEREVNVGGSDEDLEDRTLTIVSGTDLVNISfinFVAESEEVAKI 108

                          90
                  ....*....|
gi 167900458  215 WVSGLRYLVS 224
Cdd:cd13361   109 WTEGLFKLAH 118

EFh_PI-PLCepsilon

cd16203

EF-hand motif found in phosphoinositide phospholipase C epsilon 1 (PI-PLC-epsilon1); ...

331-386

4.40e-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: 42.31 E-value: 4.40e-04

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 167900458  331 LDANDLMLFLEAEQGvTHITEDMCLDIIRRYELSEDGRQKGFLAIDGFTQYLLSPE 386
Cdd:cd16203   120 LTISQLKDFLENHQM-EHITEEEAIKIIQRHEPDPILRSKNCLSFEGFARYLMDKD 174

PLN03008

Phospholipase D delta

748-873

7.42e-04

Phospholipase D delta

Pssm-ID: 178585 [Multi-domain] Cd Length: 868 Bit Score: 43.54 E-value: 7.42e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  748 DPYVCVeihgIPADCCEQRTKtVQQNSDNPIFDETFEFQVNLPeLTMVRFVILDDDYIGDEFIGQYTIPFECLQPGYR-- 825
Cdd:PLN03008   78 DPYVTV----VVPQATLARTR-VLKNSQEPLWDEKFNISIAHP-FAYLEFQVKDDDVFGAQIIGTAKIPVRDIASGERis 151

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 167900458  826 -HVPLRSFVGDIMEHVT-LFVHIAITN-------RSG-GGKPQKRSLS-----VRMGKKVREY 873
Cdd:PLN03008  152 gWFPVLGASGKPPKAETaIFIDMKFTPfdqihsyRCGiAGDPERRGVRrtyfpVRKGSQVRLY 214

EFh_PI-PLCbeta3

cd16210

EF-hand motif found in phosphoinositide phospholipase C beta 3 (PI-PLC-beta3); PI-PLC-beta3, ...

311-382

1.02e-03

EF-hand motif found in phosphoinositide phospholipase C beta 3 (PI-PLC-beta3); PI-PLC-beta3, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3, or phospholipase C-beta-3 (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. PI-PLC-beta3 associates with CXC chemokine receptor 2 (CXCR2) and Na+/H+ exchanger regulatory factor-1 (NHERF1) to form macromolecular complexes at the plasma membrane of pancreatic cancer cells, which functionally couple chemokine signaling to PI-PLC-beta3-mediated signaling cascade. Moreover, PI-PLC-beta3 directly interacts with the M3 muscarinic receptor (M3R), a prototypical G alpha-q-coupled receptor that promotes PI-PLC-beta3 localization to the plasma membrane. This binding can alter G alpha-q-dependent PLC activation. Furthermore, PI-PLC-beta3 inhibits the proliferation of hematopoietic stem cells (HSCs) and myeloid cells through the interaction of SH2-domain-containing protein phosphatase 1 (SHP-1) and signal transducer and activator of transcription 5 (Stat5), and the augment of the dephosphorylating activity of SHP-1 toward Stat5, leading to the inactivation of Stat5. It is also involved in atopic dermatitis (AD) pathogenesis via regulating the expression of periostin in fibroblasts and thymic stromal lymphopoietin (TSLP) in keratinocytes. In addition, PI-PLC-beta3 mediates the thrombin-induced Ca2+ response in glial cells. PI-PLC-beta3 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: 320040 Cd Length: 151 Bit Score: 40.67 E-value: 1.02e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  311 LCTRPEVYFLLVQI-SKNKEYLDANDLMLFLEAEQGVTHITE--------DMCLDIIRRYELSEDGRQKGFLAIDGFTQY 381
Cdd:cd16210    67 LCLRPDIDKILLEIgAKGKPYLTLEQLMDFINQKQRDPRLNEvlypplrpSQVRQLIEKYEPNQQFLERDQMSMEGFSRY 146


                  .
gi 167900458  382 L 382
Cdd:cd16210   147 L 147

C2A_Synaptotagmin-1-5-6-9-10

cd08385

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...

724-816

1.15e-03

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis as do synaptotagmins 5, 6, and 10. It is distinguished from the other synaptotagmins by having an N-glycosylated N-terminus. Synaptotagmins 5, 6, and 10, members of class 3 synaptotagmins, are located primarily in the brain and localized to the active zone and plasma membrane. They is distinguished from the other synaptotagmins by having disulfide bonds at its N-terminus. Synaptotagmin 6 also regulates the acrosome reaction, a unique Ca2+-regulated exocytosis, in sperm. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. 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: 176031 [Multi-domain] Cd Length: 124 Bit Score: 39.94 E-value: 1.15e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  724 LHIKIISGQNFPkpkgacAK--GDVIDPYVCVEIhgIPADCCEQRTKtVQQNSDNPIFDETFEFQVNLPELT--MVRFVI 799
Cdd:cd08385    18 LTVGIIQAADLP------AMdmGGTSDPYVKVYL--LPDKKKKFETK-VHRKTLNPVFNETFTFKVPYSELGnkTLVFSV 88

                          90
                  ....*....|....*...
gi 167900458  800 LD-DDYIGDEFIGQYTIP 816
Cdd:cd08385    89 YDfDRFSKHDLIGEVRVP 106

EFh_NorpA_like

cd16212

EF-hand motif found in Drosophila melanogaster No receptor potential A protein (NorpA) and ...

311-386

1.34e-03

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: 40.61 E-value: 1.34e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  311 LCTRPEVYFLLVQISKNK-EYLDANDLMLFLEAEQGVTHI--------TEDMCLDIIRRYELSEDGRQKGFLAIDGFTQY 381
Cdd:cd16212    69 ICPRNDIEELFTSITKGKgEHISLAQLINFMNDKQRDPRLneilyplyDEKRCTEIIKAYEQNEENIKNKRMSKDGFIRY 148


                  ....*
gi 167900458  382 LLSPE 386
Cdd:cd16212   149 LMSDE 153

C2A_RIM1alpha

cd04031

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...

724-816

1.80e-03

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: 39.54 E-value: 1.80e-03

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 167900458  724 LHIKIISGQNFPkpkgACAKGDVIDPYVCVEIHGIPADCCEQRTKTVQqNSDNPIFDETFEFQVNLPELTMVRF--VIL- 800
Cdd:cd04031    18 LIVTVLQARDLP----PRDDGSLRNPYVKVYLLPDRSEKSKRRTKTVK-KTLNPEWNQTFEYSNVRRETLKERTleVTVw 92

                          90
                  ....*....|....*..
gi 167900458  801 D-DDYIGDEFIGQYTIP 816
Cdd:cd04031    93 DyDRDGENDFLGEVVID 109

C2B_Munc13

cd04027

C2 domain second repeat in Munc13 (mammalian uncoordinated) proteins; C2-like domains are ...

748-815

4.26e-03

C2 domain second repeat in Munc13 (mammalian uncoordinated) 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 second C2 repeat, C2B, and has a type-II topology.

Pssm-ID: 175993 [Multi-domain] Cd Length: 127 Bit Score: 38.32 E-value: 4.26e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 167900458  748 DPYVCVEIHGIpadccEQRTKTVQQNSdNPIFDETFEFQV-NLPELTMVRFVILDDDYIG----------DEFIGQYTI 815
Cdd:cd04027    23 DPYVTVQVGKT-----KKRTKTIPQNL-NPVWNEKFHFEChNSSDRIKVRVWDEDDDIKSrlkqkftresDDFLGQTII 95

C2A_Synaptotagmin-4-11

cd08388

C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a ...

748-816

7.62e-03

C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmins 4 and 11, class 4 synaptotagmins, are located in the brain. Their functions are unknown. They are distinguished from the other synaptotagmins by having and Asp to Ser substitution in their C2A domains. 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: 176034 [Multi-domain] Cd Length: 128 Bit Score: 37.72 E-value: 7.62e-03

                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 167900458  748 DPYVCVEIhgIPADccEQRTKT-VQQNSDNPIFDETFEF----QVNLPELTMvRFVILD-DDYIGDEFIGQYTIP 816
Cdd:cd08388    39 DPYVKLQL--LPEK--EHKVKTrVLRKTRNPVYDETFTFygipYNQLQDLSL-HFAVLSfDRYSRDDVIGEVVCP 108

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