NCBI Conserved Domain Search

Conserved domains on [gi|14249340|ref|NP_116115|]

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1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-4 [Homo sapiens]

Protein Classification

PLC family C2 domain-containing protein; phosphoinositide-specific phospholipase C family protein( domain architecture ID 11598583)

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); phosphoinositide-specific phospholipase C (PLC) family protein is involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG)

Graphical summary

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List of domain hits

Name

Accession

Description

Interval

E-value

PI-PLCc_GDPD_SF super family

cl14615

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

289-596

0e+00

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

The actual alignment was detected with superfamily member cd08631:

Pssm-ID: 472694 [Multi-domain] Cd Length: 258 Bit Score: 543.77 E-value: 0e+00

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 289 YQDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRILFKDVVATVA 368
Cdd:cd08631   1 YQDMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDGPNGEPIVYHGHTFTSKILFKDVVAAVA 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 369 QYAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDGVLPTQLPSPEELRRKILVKGKKLtleedleyeee 448
Cdd:cd08631  81 QYAFQVSDYPVILSLENHCGVEQQQTMAQHLTEILGEKLLSTTLDGVLPTQLPSPEELRGKILLKGKKI----------- 149

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 449 eaepeleeselalesqfetepepqeqnlqnkdkkkkskpILCPALSSLVIYLKSVSFRSFTHSKEHYHFYEISSFSETKA 528
Cdd:cd08631 150 ---------------------------------------RLSPELSDCVIYCKSVSFRSFTHSREHYHFYEISSFTETKA 190

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 14249340 529 KRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQN 596
Cdd:cd08631 191 RKLIREAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQEMWNAGCQMVALNFQTAGLEMDLNDGLFRQN 258

EFh_PI-PLC super family

cl28895

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

138-277

1.19e-87

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 cd16219:

Pssm-ID: 333715 [Multi-domain] Cd Length: 140 Bit Score: 272.49 E-value: 1.19e-87

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 138 WLSDWFQRGDKNQDGKMSFQEVQRLLHLMNVEMDQEYAFSLFQAADTSQSGTLEGEEFVQFYKALTKRAEVQELFESFSA 217
Cdd:cd16219   1 WIRDWFQKADKNKDGRMNFKEVRDLLKMMNVDMNEEHALRLFQMADKSESGTLEGEEFVLFYKALTQREDVLKIFQDFSA 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 218 DGQKLTLLEFLDFLQEEQKERDCTSELALELIDRYEPSDSGKLRHVLSMDGFLSYLCSKD 277
Cdd:cd16219  81 DGQKLTLLEFVDFLQQEQLERENTEELAMELIDRYEPSDTAKKLHALSIDGFLMYLCSPE 140

PH_PLC_delta

cd13363

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

18-133

3.47e-60

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: 198.70 E-value: 3.47e-60

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  18 MQEGMPMRKVRSKSWKKLRYFRLQNDGMTVWHARQ-ARGSAKPSFSISDVETIRNGHDSELLRSLAEELPLEQGFTIVFH 96
Cdd:cd13363   1 LLQGSPLLKVRSRSWKKERFYKLQEDCKTVWHESKkTRSNSKQTFSIEDIESVREGHQSEGLRKYAEAFPEDRCFSIVFK 80

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 14249340  97 GRRSNLDLMANSVEEAQIWMRGLQLLVDLVTSMDHQE 133
Cdd:cd13363  81 GRRKNLDLIAPSEEEAQRWVRGLEKLIARLTNMSQRE 117

C2_PLC_like

cd00275

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

626-751

1.29e-51

C2 domain present in Phosphoinositide-specific phospholipases C (PLC); PLCs are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG). 1,4,5-IP3 and DAG are second messengers in eukaryotic signal transduction cascades. PLC is composed of a N-terminal PH domain followed by a series of EF hands, a catalytic TIM barrel and a C-terminal C2 domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-II topology.

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 175.81 E-value: 1.29e-51

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 626 AQTLLIQVISGQQLPKvDKTKEGSIVDPLVKVQIFGV-RLDTARQETNYVENNGFNPYWGQTLCFRVLVPELAMLRFVVM 704
Cdd:cd00275   1 PLTLTIKIISGQQLPK-PKGDKGSIVDPYVEVEIHGLpADDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVY 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 14249340 705 DYDwKSRNDFIGQYTLPWTCMQQGYRHIHLLSKDGISLRPASIFVYI 751
Cdd:cd00275  80 DED-SGDDDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHI 125

Name

Accession

Description

Interval

E-value

PI-PLCc_delta4

cd08631

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

289-596

0e+00

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: 543.77 E-value: 0e+00

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 289 YQDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRILFKDVVATVA 368
Cdd:cd08631   1 YQDMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDGPNGEPIVYHGHTFTSKILFKDVVAAVA 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 369 QYAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDGVLPTQLPSPEELRRKILVKGKKLtleedleyeee 448
Cdd:cd08631  81 QYAFQVSDYPVILSLENHCGVEQQQTMAQHLTEILGEKLLSTTLDGVLPTQLPSPEELRGKILLKGKKI----------- 149

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 449 eaepeleeselalesqfetepepqeqnlqnkdkkkkskpILCPALSSLVIYLKSVSFRSFTHSKEHYHFYEISSFSETKA 528
Cdd:cd08631 150 ---------------------------------------RLSPELSDCVIYCKSVSFRSFTHSREHYHFYEISSFTETKA 190

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 14249340 529 KRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQN 596
Cdd:cd08631 191 RKLIREAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQEMWNAGCQMVALNFQTAGLEMDLNDGLFRQN 258

EFh_PI-PLCdelta4

cd16219

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

138-277

1.19e-87

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: 272.49 E-value: 1.19e-87

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 138 WLSDWFQRGDKNQDGKMSFQEVQRLLHLMNVEMDQEYAFSLFQAADTSQSGTLEGEEFVQFYKALTKRAEVQELFESFSA 217
Cdd:cd16219   1 WIRDWFQKADKNKDGRMNFKEVRDLLKMMNVDMNEEHALRLFQMADKSESGTLEGEEFVLFYKALTQREDVLKIFQDFSA 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 218 DGQKLTLLEFLDFLQEEQKERDCTSELALELIDRYEPSDSGKLRHVLSMDGFLSYLCSKD 277
Cdd:cd16219  81 DGQKLTLLEFVDFLQQEQLERENTEELAMELIDRYEPSDTAKKLHALSIDGFLMYLCSPE 140

PI-PLC-X

pfam00388

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

292-434

2.26e-85

Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to form a single structural unit.

Pssm-ID: 459795 [Multi-domain] Cd Length: 142 Bit Score: 266.29 E-value: 2.26e-85

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340   292 MTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRILFKDVVATVAQYA 371
Cdd:pfam00388   1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 14249340   372 FQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDGvLPTQLPSPEELRRKILVKG 434
Cdd:pfam00388  81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLDD-DLTELPSPEDLKGKILIKG 142

PLN02228

Phosphoinositide phospholipase C

207-739

2.27e-83

Phosphoinositide phospholipase C

Pssm-ID: 177873 [Multi-domain] Cd Length: 567 Bit Score: 276.15 E-value: 2.27e-83

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  207 EVQELFESFSADGqKLTLLEFLDFLQEEQKERDCTSELALELIDRYEPSDSGKLRHVLSMDGFLSYLCSkDGDIFNPACL 286
Cdd:PLN02228  25 SIKRLFEAYSRNG-KMSFDELLRFVSEVQGERHAGLDYVQDIFHSVKHHNVFHHHGLVHLNAFYRYLFS-DTNSPLPMSG 102

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  287 PIYQDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSG-EPVVYHGHTLTSRILFKDVVA 365
Cdd:PLN02228 103 QVHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSGnAAEVRHGRTLTSHEDLQKCLN 182

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  366 TVAQYAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDGVlpTQLPSPEELRRKILVKGKKLTLEEDLEY 445
Cdd:PLN02228 183 AIKDNAFQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGMLFRCTSEST--KHFPSPEELKNKILISTKPPKEYLESKT 260

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  446 EEEEAEPELEESELALESQFETEPEPQEQNLQnkdkkkkskpilcpalSSLVIYLKSVSFRSFTH--------SKEHYHF 517
Cdd:PLN02228 261 VQTTRTPTVKETSWKRVADAENKILEEYKDEE----------------SEAVGYRDLIAIHAANCkdplkdclSDDPEKP 324

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  518 YEIsSFSETKAKRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQNG 597
Cdd:PLN02228 325 IRV-SMDEQWLETMVRTRGTDLVRFTQRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFNMQGHGKQLWIMQGMFRANG 403

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  598 GCGYVLKPDFLRDIQSSFHPEKPIsPFKAqTLLIQVISGQ----QLPKvDKTKEGSIVDPLVKVQIFGVRLDTARQETNY 673
Cdd:PLN02228 404 GCGYVKKPRILLDEHTLFDPCKRL-PIKT-TLKVKIYTGEgwdlDFHL-THFDQYSPPDFFVKIGIAGVPRDTVSYRTET 480

                        490       500       510       520       530       540
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 14249340  674 VENNGFnPYWG-QTLCFRVLVPELAMLRFVVMDYDWKSRNDFIGQYTLPWTCMQQGYRHIHLLSKDG 739
Cdd:PLN02228 481 AVDQWF-PIWGnDEFLFQLRVPELALLWFKVQDYDNDTQNDFAGQTCLPLPELKSGVRAVRLHDRAG 546

PLCXc

smart00148

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

292-435

2.13e-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: 216.38 E-value: 2.13e-66

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340    292 MTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRILFKDVVATVAQYA 371
Cdd:smart00148   1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 14249340    372 FQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDGVLpTQLPSPEELRRKILVKGK 435
Cdd:smart00148  81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSL-EVLPSPEQLRGKILLKVR 143

PH_PLC_delta

cd13363

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

18-133

3.47e-60

Pssm-ID: 270169 Cd Length: 117 Bit Score: 198.70 E-value: 3.47e-60

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  18 MQEGMPMRKVRSKSWKKLRYFRLQNDGMTVWHARQ-ARGSAKPSFSISDVETIRNGHDSELLRSLAEELPLEQGFTIVFH 96
Cdd:cd13363   1 LLQGSPLLKVRSRSWKKERFYKLQEDCKTVWHESKkTRSNSKQTFSIEDIESVREGHQSEGLRKYAEAFPEDRCFSIVFK 80

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 14249340  97 GRRSNLDLMANSVEEAQIWMRGLQLLVDLVTSMDHQE 133
Cdd:cd13363  81 GRRKNLDLIAPSEEEAQRWVRGLEKLIARLTNMSQRE 117

C2_PLC_like

cd00275

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

626-751

1.29e-51

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 175.81 E-value: 1.29e-51

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 626 AQTLLIQVISGQQLPKvDKTKEGSIVDPLVKVQIFGV-RLDTARQETNYVENNGFNPYWGQTLCFRVLVPELAMLRFVVM 704
Cdd:cd00275   1 PLTLTIKIISGQQLPK-PKGDKGSIVDPYVEVEIHGLpADDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVY 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 14249340 705 DYDwKSRNDFIGQYTLPWTCMQQGYRHIHLLSKDGISLRPASIFVYI 751
Cdd:cd00275  80 DED-SGDDDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHI 125

EF-hand_like

pfam09279

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

198-282

1.64e-42

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: 148.93 E-value: 1.64e-42

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340   198 FYKALTKRAEVQELFESFSADGQKLTLLEFLDFLQEEQKERDCTSELALELIDRYEPSDSGKLRHVLSMDGFLSYLCSKD 277
Cdd:pfam09279   1 FYKMLTQREEIDEIFQEYSGDGQKLSLDELVDFLREEQREEDASPALALSLIERYEPSETAKKQHAMTKDGFLMYLCSPD 80


                  ....*
gi 14249340   278 GDIFN 282
Cdd:pfam09279  81 GSIFN 85

smart00239

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

628-734

5.50e-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: 96.79 E-value: 5.50e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340    628 TLLIQVISGQQLPKVDKtkeGSIVDPLVKVQIFGVRLDTARqeTNYVENNGfNPYWGQTLCFRVLVPELAMLRFVVMDYD 707
Cdd:smart00239   1 TLTVKIISARNLPPKDK---GGKSDPYVKVSLDGDPKEKKK--TKVVKNTL-NPVWNETFEFEVPPPELAELEIEVYDKD 74

                           90       100
                   ....*....|....*....|....*..
gi 14249340    708 WKSRNDFIGQYTLPWTCMQQGYRHIHL 734
Cdd:smart00239  75 RFGRDDFIGQVTIPLSDLLLGGRHEKL 101

pfam00168

C2 domain;

627-733

6.38e-20

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 85.45 E-value: 6.38e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340   627 QTLLIQVISGQQLPKVDKTkegSIVDPLVKVQIFGvrlDTARQETNYVENNgFNPYWGQTLCFRVLVPELAMLRFVVMDY 706
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGN---GTSDPYVKVYLLD---GKQKKKTKVVKNT-LNPVWNETFTFSVPDPENAVLEIEVYDY 73

                          90       100
                  ....*....|....*....|....*..
gi 14249340   707 DWKSRNDFIGQYTLPWTCMQQGYRHIH 733
Cdd:pfam00168  74 DRFGRDDFIGEVRIPLSELDSGEGLDG 100

FRQ1

COG5126

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

126-233

1.50e-12

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

Pssm-ID: 444056 [Multi-domain] Cd Length: 137 Bit Score: 65.58 E-value: 1.50e-12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 126 VTSMDHQERLDQWLSDWFQRGDKNQDGKMSFQEVQRLLHLMNVEMDQEYAFSLFQAADTSQSGTLEGEEFVQFYKAL-TK 204
Cdd:COG5126  22 LERDDFEALFRRLWATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTALgVS 101

                        90       100       110
                ....*....|....*....|....*....|
gi 14249340 205 RAEVQELFESFSADGQ-KLTLLEFLDFLQE 233
Cdd:COG5126 102 EEEADELFARLDTDGDgKISFEEFVAAVRD 131

smart00233

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...

26-124

1.78e-08

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

Pssm-ID: 214574 [Multi-domain] Cd Length: 102 Bit Score: 52.55 E-value: 1.78e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340     26 KVRSKSWKKlRYFRLQNDGMTVWHARQARGSAKPSFSIS-DVETIRNGHDSEllrslaeELPLEQGFTIVfHGRRSNLDL 104
Cdd:smart00233  12 GGGKKSWKK-RYFVLFNSTLLYYKSKKDKKSYKPKGSIDlSGCTVREAPDPD-------SSKKPHCFEIK-TSDRKTLLL 82

                           90       100
                   ....*....|....*....|
gi 14249340    105 MANSVEEAQIWMRGLQLLVD 124
Cdd:smart00233  83 QAESEEEREKWVEALRKAIA 102

pfam00169

PH domain; PH stands for pleckstrin homology.

17-123

6.19e-07

PH domain; PH stands for pleckstrin homology.

Pssm-ID: 459697 [Multi-domain] Cd Length: 105 Bit Score: 48.33 E-value: 6.19e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340    17 LMQEGMPMRKV--RSKSWKKlRYFRLQNDGMTVWHARQARGSAKPSFSIsDVETIRNGHDSELlrslaEELPLEQGFTIV 94
Cdd:pfam00169   1 VVKEGWLLKKGggKKKSWKK-RYFVLFDGSLLYYKDDKSGKSKEPKGSI-SLSGCEVVEVVAS-----DSPKRKFCFELR 73

                          90       100       110
                  ....*....|....*....|....*....|.
gi 14249340    95 FHGRRSN--LDLMANSVEEAQIWMRGLQLLV 123
Cdd:pfam00169  74 TGERTGKrtYLLQAESEEERKDWIKAIQSAI 104

UgpQ

COG0584

Glycerophosphoryl diester phosphodiesterase [Lipid transport and metabolism];

319-354

9.21e-03

Glycerophosphoryl diester phosphodiesterase [Lipid transport and metabolism];

Pssm-ID: 440349 [Multi-domain] Cd Length: 238 Bit Score: 38.70 E-value: 9.21e-03

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 14249340 319 SVEGYIRALKRGCRCVEVDVW---DgpsGEPVVYHGHTL 354
Cdd:COG0584  19 TLAAFRAALELGADGIELDVQltkD---GVLVVFHDPTL 54

Name

Accession

Description

Interval

E-value

PI-PLCc_delta4

cd08631

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

289-596

0e+00

Pssm-ID: 176568 [Multi-domain] Cd Length: 258 Bit Score: 543.77 E-value: 0e+00

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 289 YQDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRILFKDVVATVA 368
Cdd:cd08631   1 YQDMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDGPNGEPIVYHGHTFTSKILFKDVVAAVA 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 369 QYAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDGVLPTQLPSPEELRRKILVKGKKLtleedleyeee 448
Cdd:cd08631  81 QYAFQVSDYPVILSLENHCGVEQQQTMAQHLTEILGEKLLSTTLDGVLPTQLPSPEELRGKILLKGKKI----------- 149

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 449 eaepeleeselalesqfetepepqeqnlqnkdkkkkskpILCPALSSLVIYLKSVSFRSFTHSKEHYHFYEISSFSETKA 528
Cdd:cd08631 150 ---------------------------------------RLSPELSDCVIYCKSVSFRSFTHSREHYHFYEISSFTETKA 190

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 14249340 529 KRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQN 596
Cdd:cd08631 191 RKLIREAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQEMWNAGCQMVALNFQTAGLEMDLNDGLFRQN 258

PI-PLCc_delta

cd08593

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

289-596

7.67e-179

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: 511.50 E-value: 7.67e-179

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 289 YQDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRILFKDVVATVA 368
Cdd:cd08593   1 YQDMTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDGPDGEPIIYHGHTLTSKILFKDVIQAIR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 369 QYAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDGVLpTQLPSPEELRRKILVKGKKLtleedleyeee 448
Cdd:cd08593  81 EYAFKVSPYPVILSLENHCSVEQQKVMAQHLKSILGDKLLTQPLDGVL-TALPSPEELKGKILVKGKKL----------- 148

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 449 eaepeleeselalesqfetepepqeqnlqnkdkkkkskpILCPALSSLVIYLKSVSFRSFTHSKEHYHFYEISSFSETKA 528
Cdd:cd08593 149 ---------------------------------------KLAKELSDLVIYCKSVHFKSFEHSKENYHFYEMSSFSESKA 189

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 14249340 529 KRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQN 596
Cdd:cd08593 190 LKLAQESGNEFVRHNKRQLSRIYPAGLRTDSSNYDPQEMWNVGCQIVALNFQTPGEEMDLNDGLFRQN 257

PI-PLCc_eukaryota

cd08558

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

289-596

4.37e-142

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: 416.47 E-value: 4.37e-142

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 289 YQDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRILFKDVVATVA 368
Cdd:cd08558   1 YQDMTQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGHTLTSKILFKDVIEAIK 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 369 QYAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDGvLPTQLPSPEELRRKILVKGKKltleedleyeee 448
Cdd:cd08558  81 EYAFVTSPYPVILSLENHCSLEQQKKMAQILKEIFGDKLLTPPLDE-NPVQLPSPEQLKGKILIKGKK------------ 147

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 449 eaepeleeselalesqfetepepqeqnlqnkdkkkkskpilcpalsslviylksvsfrsfthskehyhfYEISSFSETKA 528
Cdd:cd08558 148 ---------------------------------------------------------------------YHMSSFSETKA 158

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 14249340 529 KRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQN 596
Cdd:cd08558 159 LKLLKESPEEFVKYNKRQLSRVYPKGTRVDSSNYNPQPFWNAGCQMVALNYQTPDLPMQLNQGKFEQN 226

PI-PLCc_delta1

cd08629

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

289-596

5.51e-123

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: 368.59 E-value: 5.51e-123

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 289 YQDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRILFKDVVATVA 368
Cdd:cd08629   1 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVLRAIR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 369 QYAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDGVLpTQLPSPEELRRKILVKGKKLTleedleyeee 448
Cdd:cd08629  81 DYAFKASPYPVILSLENHCSLEQQRVMARHLRAILGPILLDQPLDGVT-TSLPSPEQLKGKILLKGKKLK---------- 149

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 449 eaepeleeselalesqfetepepqeqnlqnkdkkkkskpiLCPALSSLVIYLKSVSFRSFTHSKEHYH-FYEISSFSETK 527
Cdd:cd08629 150 ----------------------------------------LVPELSDMIIYCKSVHFGGFSSPGTSGQaFYEMASFSESR 189

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 14249340 528 AKRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQN 596
Cdd:cd08629 190 ALRLLQESGNGFVRHNVSCLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYLGCFQDN 258

PI-PLCc_PRIP_metazoa

cd08597

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

290-596

4.75e-122

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: 366.36 E-value: 4.75e-122

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 290 QDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRILFKDVVATVAQ 369
Cdd:cd08597   2 QDMTQPLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDGPNGEPVIYHGHTLTSKISFRSVIEAINE 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 370 YAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDGVLpTQLPSPEELRRKILVKGKKltleedleyeeee 449
Cdd:cd08597  82 YAFVASEYPLILCIENHCSEKQQLVMAQYLKEIFGDKLYTEPPNEGE-SYLPSPHDLKGKIIIKGKK------------- 147

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 450 aepeleeselalesqfetepepqeqnlqnkdkkkKSKPILCPALSSLVIYLKSVSFRSFTHSKEHYHFYEISSFSETKAK 529
Cdd:cd08597 148 ----------------------------------LKRRKLCKELSDLVSLCKSVRFQDFPTSAQNQKYWEVCSFSENLAR 193

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 14249340 530 RLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQN 596
Cdd:cd08597 194 RLANEFPEDFVNYNKKFLSRVYPSPMRVDSSNYNPQDFWNCGCQIVAMNYQTPGLMMDLNTGKFLEN 260

PI-PLCc_delta3

cd08630

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

289-596

6.53e-122

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: 365.88 E-value: 6.53e-122

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 289 YQDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRILFKDVVATVA 368
Cdd:cd08630   1 FQDMSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVIQAVR 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 369 QYAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDGVLPTQLPSPEELRRKILVKGKKltleedleyeee 448
Cdd:cd08630  81 QHAFTASPYPVILSLENHCGLEQQAAMARHLQTILGDMLVTQPLDSLNPEELPSPEELKGRVLVKGKK------------ 148

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 449 eaepeleeselalesqfetepepqeqnLQnkdkkkkskpiLCPALSSLVIYLKSVSFRSFTHSKEHYHFYEISSFSETKA 528
Cdd:cd08630 149 ---------------------------LQ-----------ISPELSALAVYCQATRLRTLEPAPVQPQPCQVSSLSERKA 190

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 14249340 529 KRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQN 596
Cdd:cd08630 191 KKLIREAGNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLVALNFQTPGYEMDLNAGRFLVN 258

PI-PLCc_zeta

cd08595

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

289-596

2.02e-120

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: 361.95 E-value: 2.02e-120

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 289 YQDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRILFKDVVATVA 368
Cdd:cd08595   1 YQDMDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDGADNEPVVYHGYTLTSKILFKEVITTVE 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 369 QYAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDGVLPTQLPSPEELRRKILVKGKKLtleedleyeee 448
Cdd:cd08595  81 KYAFEKSDYPVVLSLENHCSTEQQEIMAHYLVSILGEKLLRAPIDDPATGELPSPEALKFKILVKNKKK----------- 149

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 449 eaepeleeselalesqfetepepqeqnlqnkdkkkkskpiLCPALSSLVIYLKSVSFRSFTHSKEHYHFYEISSFSETKA 528
Cdd:cd08595 150 ----------------------------------------IAKALSDLVIYTKSEKFCSFTHSRDNQHSYENNSIGENKA 189

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 14249340 529 KRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQN 596
Cdd:cd08595 190 RKLLKSSGADFVGHTQRFITRIYPKGTRASSSNYNPQEFWNVGCQMVALNFQTLGAPMDLQNGKFLDN 257

PI-PLCc_beta

cd08591

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

289-596

4.46e-109

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: 332.77 E-value: 4.46e-109

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 289 YQDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDG--PSGEPVVYHGHTLTSRILFKDVVAT 366
Cdd:cd08591   1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGkgEDEEPIITHGKTMCTEILFKDVIEA 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 367 VAQYAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDG--VLP-TQLPSPEELRRKILVKGKKltleedl 443
Cdd:cd08591  81 IAETAFKTSEYPVILSFENHCSSKQQAKMAEYCREIFGDLLLTEPLEKypLEPgVPLPSPNDLKRKILIKNKK------- 153

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 444 eyeeeeaepeleeselalesqfetepepqeqnlqnkdkkkkskpilcpaLSSLVIYLKSVSFRSFTHSKEHYHFYEISSF 523
Cdd:cd08591 154 -------------------------------------------------LSSLVNYIQPVKFQGFEVAEKRNKHYEMSSF 184

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 14249340 524 SETKAKRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQN 596
Cdd:cd08591 185 NESKGLGYLKKSPIEFVNYNKRQLSRIYPKGTRVDSSNYMPQIFWNAGCQMVALNFQTPDLPMQLNQGKFEYN 257

PI-PLC1c_yeast

cd08598

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

289-596

6.23e-103

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: 315.73 E-value: 6.23e-103

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 289 YQDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRILFKDVVATVA 368
Cdd:cd08598   1 EEDLSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDGDDGEPVVTHGYTLTSSVPFRDVCRAIK 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 369 QYAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDGVLPtQLPSPEELRRKILVKGKKLtleedleyeee 448
Cdd:cd08598  81 KYAFVTSPYPLILSLEVHCDAEQQERMVEIMKETFGDLLVTEPLDGLED-ELPSPEELRGKILIKVKKE----------- 148

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 449 eaepeleeselalesqfetepepqeqnlqnkdkkkkskpilcpalsslviylksvsfrsfthSKEHYHFYeisSFSETKA 528
Cdd:cd08598 149 --------------------------------------------------------------SKTPNHIF---SLSERSL 163

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 14249340 529 KRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQN 596
Cdd:cd08598 164 LKLLKDKRAALDKHNRRHLMRVYPSGTRISSSNFNPLPFWRAGVQMVALNWQTYDLGMQLNEAMFAGS 231

PI-PLCc_gamma

cd08592

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

290-596

1.58e-99

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: 306.66 E-value: 1.58e-99

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 290 QDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRILFKDVVATVAQ 369
Cdd:cd08592   2 QDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGPDGMPIIYHGHTLTSKIKFMDVLKTIKE 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 370 YAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDgVLPTQLPSPEELRRKILVKGKKLtleedleyeeee 449
Cdd:cd08592  82 HAFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDMLLTQPVD-RNADQLPSPNQLKRKIIIKHKKL------------ 148

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 450 aepeleeselalesqfetepepqeqnlqnkdkkkkskpilcpalsslviylksvsfrsfthskehyhFYEISSFSETKA- 528
Cdd:cd08592 149 -------------------------------------------------------------------FYEMSSFPETKAe 161

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 14249340 529 KRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQN 596
Cdd:cd08592 162 KYLNRQKGKIFLKYNRRQLSRVYPKGQRVDSSNYDPVPMWNCGSQMVALNFQTPDKPMQLNQALFMLN 229

PI-PLCc_eta2

cd08633

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

290-596

9.11e-99

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: 305.81 E-value: 9.11e-99

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 290 QDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRILFKDVVATVAQ 369
Cdd:cd08633   2 QDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 370 YAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDGVLPTQLPSPEELRRKILVKGKKltleedleyeeee 449
Cdd:cd08633  82 YAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLDLSSVISNDCTRLPSPEILKGKILVKGKK------------- 148

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 450 aepeleeselalesqfetepepqeqnlqnkdkkkkskpiLCPALSSLVIYLKSVSFRSFthSKEHYHFYEISSFSETKAK 529
Cdd:cd08633 149 ---------------------------------------LSRALSDLVKYTKSVRVHDI--ETEATSSWQVSSFSETKAH 187

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 14249340 530 RLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQN 596
Cdd:cd08633 188 QILQQKPAQYLRFNQRQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKFSAN 254

PI-PLCc_eta

cd08594

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

289-596

2.99e-98

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: 303.26 E-value: 2.99e-98

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 289 YQDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRILFKDVVATVA 368
Cdd:cd08594   1 NQDMTQPLSHYFIASSHNTYLTGDQLLSQSRVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKILFRDVIETIN 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 369 QYAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDGVLPTQLPSPEELRRKILVKGKKltleedleyeee 448
Cdd:cd08594  81 KYAFIKNEYPVILSIENHCSVQQQKKMAQYLKEILGDKLDLSSVISGDSKQLPSPQSLKGKILIKGKK------------ 148

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 449 eaepeleeselalesqfetepepqeqnlqnkdkkkkskpilcpalsslviylksvsfrsfthskehyhfYEISSFSETKA 528
Cdd:cd08594 149 ---------------------------------------------------------------------WQVSSFSETRA 159

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 14249340 529 KRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQN 596
Cdd:cd08594 160 HQIVQQKAAQFLRFNQRQLSRIYPSAYRIDSSNFNPQPYWNAGCQLVALNYQTEGRMLQLNRAKFRAN 227

PI-PLCc_eta1

cd08632

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

289-596

3.02e-93

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: 291.55 E-value: 3.02e-93

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 289 YQDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRILFKDVVATVA 368
Cdd:cd08632   1 NQDMDQPLCNYFIASSHNTYLTGDQLLSQSKVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKITFRDVIETIN 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 369 QYAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDGVLPTQLPSPEELRRKILVKGKKltleedleyeee 448
Cdd:cd08632  81 KYAFVKNEFPVILSIENHCSIQQQKKIAQYLKEIFGDKLDLSSVLTGDPKQLPSPQLLKGKILVKGKK------------ 148

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 449 eaepeleeselalesqfetepepqeqnlqnkdkkkkskpiLCPALSSLVIYLKSVSFRSFTHSKEHYHfyeISSFSETKA 528
Cdd:cd08632 149 ----------------------------------------LCRDLSDLVVYTNSVAAQDIVDDGSTGN---VLSFSETRA 185

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 14249340 529 KRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQN 596
Cdd:cd08632 186 HQLVQQKAEQFMTYNQKQLTRIYPSAYRIDSSNFNPLPYWNVGCQLVALNYQSEGRMMQLNRAKFMVN 253

PI-PLCc_beta4

cd08626

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

289-596

3.95e-88

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: 278.19 E-value: 3.95e-88

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 289 YQDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPS--GEPVVYHGHTLTSRILFKDVVAT 366
Cdd:cd08626   1 YQDMDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGKGedQEPIITHGKAMCTDILFKDVIQA 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 367 VAQYAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDG--VLPTQ-LPSPEELRRKILVKGKKltleedl 443
Cdd:cd08626  81 IKDTAFVTSDYPVILSFENHCSKPQQYKLAKYCEEIFGDLLLTKPLEShpLEPGVpLPSPNKLKRKILIKNKR------- 153

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 444 eyeeeeaepeleeselalesqfetepepqeqnlqnkdkkkkskpilcpaLSSLVIYLKSVSFRSFTHSKEHYHFYEISSF 523
Cdd:cd08626 154 -------------------------------------------------LSSLVNYAQPVKFQGFDVAEERNIHFNMSSF 184

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 14249340 524 SETKAKRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQN 596
Cdd:cd08626 185 NESVGLGYLKTSAIEFVNYNKRQMSRIYPKGTRVDSSNYMPQIFWNAGCQMVSLNFQTPDLGMQLNQGKFEYN 257

EFh_PI-PLCdelta4

cd16219

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

138-277

1.19e-87

Pssm-ID: 320049 [Multi-domain] Cd Length: 140 Bit Score: 272.49 E-value: 1.19e-87

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 138 WLSDWFQRGDKNQDGKMSFQEVQRLLHLMNVEMDQEYAFSLFQAADTSQSGTLEGEEFVQFYKALTKRAEVQELFESFSA 217
Cdd:cd16219   1 WIRDWFQKADKNKDGRMNFKEVRDLLKMMNVDMNEEHALRLFQMADKSESGTLEGEEFVLFYKALTQREDVLKIFQDFSA 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 218 DGQKLTLLEFLDFLQEEQKERDCTSELALELIDRYEPSDSGKLRHVLSMDGFLSYLCSKD 277
Cdd:cd16219  81 DGQKLTLLEFVDFLQQEQLERENTEELAMELIDRYEPSDTAKKLHALSIDGFLMYLCSPE 140

PI-PLC-X

pfam00388

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

292-434

2.26e-85

Phosphatidylinositol-specific phospholipase C, X domain; This associates with pfam00387 to form a single structural unit.

Pssm-ID: 459795 [Multi-domain] Cd Length: 142 Bit Score: 266.29 E-value: 2.26e-85

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340   292 MTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRILFKDVVATVAQYA 371
Cdd:pfam00388   1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 14249340   372 FQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDGvLPTQLPSPEELRRKILVKG 434
Cdd:pfam00388  81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLDD-DLTELPSPEDLKGKILIKG 142

PI-PLCc_gamma2

cd08628

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

290-596

1.52e-84

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: 268.46 E-value: 1.52e-84

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 290 QDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRILFKDVVATVAQ 369
Cdd:cd08628   2 QDMNNPLSHYWISSSHNTYLTGDQLRSESSTEAYIRCLRMGCRCIELDCWDGPDGKPIIYHGWTRTTKIKFDDVVQAIKD 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 370 YAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDGVlPTQLPSPEELRRKILVKGKKltleedleyeeee 449
Cdd:cd08628  82 HAFVTSEYPVILSIEEHCSVEQQRHMAKVFKEVFGDKLLMKPLEAS-ADQLPSPTQLKEKIIIKHKK------------- 147

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 450 aepeleeselalesqfetepepqeqnlqnkdkkkkskpILCPALSSLVIYLKSVSfrSFTHSKEHYHFYEISSFSETKAK 529
Cdd:cd08628 148 --------------------------------------LIAIELSDLVVYCKPTS--KTKDNLENPDFKEIRSFVETKAP 187

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 14249340 530 RLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQN 596
Cdd:cd08628 188 SIIRQKPVQLLKYNRKGLTRVYPKGQRVDSSNYDPFRLWLCGSQMVALNFQTADKYMQLNHALFSLN 254

PI-PLCc_beta2

cd08624

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

289-586

3.84e-84

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: 267.69 E-value: 3.84e-84

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 289 YQDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDG--PSGEPVVYHGHTLTSRILFKDVVAT 366
Cdd:cd08624   1 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTEILFKDAIEA 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 367 VAQYAFQTSDYPVILSLETHC-SWEQQQTMARHLTEILGEQLLSTTLD------GVlptQLPSPEELRRKILVKGKKltl 439
Cdd:cd08624  81 IAESAFKTSPYPVILSFENHVdSPKQQAKMAEYCRTIFGDMLLTEPLEkyplkpGV---PLPSPEDLRGKILIKNKK--- 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 440 eedleyeeeeaepeleeselalesqFEtepepqeqnlqnkdkkkkskpilcpALSSLVIYLKSVSFRSFTHSKEHYHFYE 519
Cdd:cd08624 155 -------------------------YE-------------------------EMSSLVNYIQPTKFVSFEFSAQKNRSYV 184

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 14249340 520 ISSFSETKAKRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEM 586
Cdd:cd08624 185 ISSFTELKAYDLLSKASVQFVEYNKRQMSRIYPKGTRMDSSNYMPQMFWNVGCQMVALNFQTMDLPM 251

PI-PLCc_epsilon

cd08596

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

290-596

1.62e-83

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: 265.94 E-value: 1.62e-83

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 290 QDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRILFKDVVATVAQ 369
Cdd:cd08596   2 EDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGDDGMPIIYHGHTLTTKIPFKDVVEAINR 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 370 YAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTL---DGVLPTQLPSPEELRRKILVKGKKLtleedleye 446
Cdd:cd08596  82 SAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLVTKFLfesDFSDDPSLPSPLQLKNKILLKNKKA--------- 152

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 447 eeeaepeleeselalesqfetepepqeqnlqnkdkkkkskpilcPALSSLVIYLKSVSFRSFTHSKehyhFYEISSFSET 526
Cdd:cd08596 153 --------------------------------------------PELSDLVIYCQAVKFPGLSTPK----CYHISSLNEN 184

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 527 KAKRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQN 596
Cdd:cd08596 185 AAKRLCRRYPQKLVQHTRCQLLRTYPAATRIDSSNPNPLIFWLHGLQLVALNYQTDDLPMHLNAAMFEAN 254

PLN02228

Phosphoinositide phospholipase C

207-739

2.27e-83

Phosphoinositide phospholipase C

Pssm-ID: 177873 [Multi-domain] Cd Length: 567 Bit Score: 276.15 E-value: 2.27e-83

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  207 EVQELFESFSADGqKLTLLEFLDFLQEEQKERDCTSELALELIDRYEPSDSGKLRHVLSMDGFLSYLCSkDGDIFNPACL 286
Cdd:PLN02228  25 SIKRLFEAYSRNG-KMSFDELLRFVSEVQGERHAGLDYVQDIFHSVKHHNVFHHHGLVHLNAFYRYLFS-DTNSPLPMSG 102

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  287 PIYQDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSG-EPVVYHGHTLTSRILFKDVVA 365
Cdd:PLN02228 103 QVHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSGnAAEVRHGRTLTSHEDLQKCLN 182

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  366 TVAQYAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDGVlpTQLPSPEELRRKILVKGKKLTLEEDLEY 445
Cdd:PLN02228 183 AIKDNAFQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGMLFRCTSEST--KHFPSPEELKNKILISTKPPKEYLESKT 260

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  446 EEEEAEPELEESELALESQFETEPEPQEQNLQnkdkkkkskpilcpalSSLVIYLKSVSFRSFTH--------SKEHYHF 517
Cdd:PLN02228 261 VQTTRTPTVKETSWKRVADAENKILEEYKDEE----------------SEAVGYRDLIAIHAANCkdplkdclSDDPEKP 324

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  518 YEIsSFSETKAKRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQNG 597
Cdd:PLN02228 325 IRV-SMDEQWLETMVRTRGTDLVRFTQRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFNMQGHGKQLWIMQGMFRANG 403

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  598 GCGYVLKPDFLRDIQSSFHPEKPIsPFKAqTLLIQVISGQ----QLPKvDKTKEGSIVDPLVKVQIFGVRLDTARQETNY 673
Cdd:PLN02228 404 GCGYVKKPRILLDEHTLFDPCKRL-PIKT-TLKVKIYTGEgwdlDFHL-THFDQYSPPDFFVKIGIAGVPRDTVSYRTET 480

                        490       500       510       520       530       540
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 14249340  674 VENNGFnPYWG-QTLCFRVLVPELAMLRFVVMDYDWKSRNDFIGQYTLPWTCMQQGYRHIHLLSKDG 739
Cdd:PLN02228 481 AVDQWF-PIWGnDEFLFQLRVPELALLWFKVQDYDNDTQNDFAGQTCLPLPELKSGVRAVRLHDRAG 546

PI-PLCc_beta3

cd08625

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

291-596

2.33e-82

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: 263.07 E-value: 2.33e-82

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 291 DMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDG--PSGEPVVYHGHTLTSRILFKDVVATVA 368
Cdd:cd08625   3 DMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGrpPEEEPFITHGFTMTTEIPFKDVIEAIA 82

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 369 QYAFQTSDYPVILSLETHC-SWEQQQTMARHLTEILGEQLLSTTLDG--VLP-TQLPSPEELRRKILVKGKKltleedle 444
Cdd:cd08625  83 ESAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDKypLVPgVQLPSPQELMGKILVKNKK-------- 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 445 yeeeeaepeleeselalesqfetepepqeqnlqnkdkkkkskpilcpaLSSLVIYLKSVSFRSFTHSKEHYHFYEISSFS 524
Cdd:cd08625 155 ------------------------------------------------MSTLVNYIEPVKFKSFEAAAKRNKFFEMSSFV 186

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 14249340 525 ETKAKRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQN 596
Cdd:cd08625 187 ETKAMEQLTKSPMEFVEYNKKQLSRIYPKGTRVDSSNYMPQLFWNVGCQMVALNFQTLDLAMQLNMGVFEYN 258

PLN02952

phosphoinositide phospholipase C

207-749

7.85e-82

phosphoinositide phospholipase C

Pssm-ID: 178538 [Multi-domain] Cd Length: 599 Bit Score: 273.03 E-value: 7.85e-82

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  207 EVQELFESFSADGQKLTLLEFLDFLQEEQKERDCTSELALELID----------RYEpsdsgklRHVLSMDGFLSYLCSK 276
Cdd:PLN02952  39 DVKDVFCKFSVGGGHMGADQLRRFLVLHQDELDCTLAEAQRIVEevinrrhhvtRYT-------RHGLNLDDFFHFLLYD 111

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  277 DgdiFNPACLP-IYQDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPV-VYHGHTL 354
Cdd:PLN02952 112 D---LNGPITPqVHHDMTAPLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPGSTKDEIlVLHGRTL 188

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  355 TSRILFKDVVATVAQYAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDGVLptQLPSPEELRRKILVKG 434
Cdd:PLN02952 189 TTPVPLIKCLKSIRDYAFSSSPYPVIITLEDHLTPDLQAKVAEMATQIFGQMLYYPESDSLV--QFPSPESLKHRIIIST 266

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  435 KKLTLEEDLEYEEEEAEPELEESELALESQ------------FETEPEPQEQNLQNKDKKKKSKPilcPALSSLV-IYLK 501
Cdd:PLN02952 267 KPPKEYLESSGPIVIKKKNNVSPSGRNSSEeteeaqtlesmlFEQEADSRSDSDQDDNKSGELQK---PAYKRLItIHAG 343

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  502 SVSFRSFTHSKEHYHFYEISSFSETKAKRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQT 581
Cdd:PLN02952 344 KPKGTLKDAMKVAVDKVRRLSLSEQELEKAATTNGQDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFNMQG 423

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  582 AGLEMDICDGHFRQNGGCGYVLKPDFLRDI---QSSFHPEKPISPFKaqTLLIQVISGQQLpKVDKTKEG----SIVDPL 654
Cdd:PLN02952 424 YGKSLWLMHGMFRANGGCGYLKKPDFLMKKgfhDEVFDPKKKLPVKK--TLKVKVYLGDGW-RLDFSHTHfdsySPPDFY 500

                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  655 VKVQIFGVRLDTARQETNYVENNgFNPYWGQTLCFRVLVPELAMLRFVVMDYDWKSRNDFIGQYTLPWTCMQQGYRHIHL 734
Cdd:PLN02952 501 TKMYIVGVPADNAKKKTKIIEDN-WYPAWNEEFSFPLTVPELALLRIEVREYDMSEKDDFGGQTCLPVSELRPGIRSVPL 579

                        570
                 ....*....|....*
gi 14249340  735 LSKDGISLRPASIFV 749
Cdd:PLN02952 580 HDKKGEKLKNVRLLM 594

PI-PLCc_gamma1

cd08627

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

290-596

3.39e-79

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: 253.41 E-value: 3.39e-79

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 290 QDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRILFKDVVATVAQ 369
Cdd:cd08627   2 EEMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKE 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 370 YAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDgVLPTQLPSPEELRRKILVKGKKLtleedleyeeee 449
Cdd:cd08627  82 HAFVTSEYPIILSIEDHCSIVQQRNMAQHFKKVFGDMLLTKPVD-INADGLPSPNQLKRKILIKHKKL------------ 148

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 450 aepeleeselalesqfetepepqeqnlqnkdkkkkskpilcpalsslviylksvsfrsfthskehyhFYEISSFSETKAK 529
Cdd:cd08627 149 -------------------------------------------------------------------YRDMSSFPETKAE 161

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 14249340 530 RLIKEA-GNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQN 596
Cdd:cd08627 162 KYVNRSkGKKFLQYNRRQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFMLG 229

PLN02222

phosphoinositide phospholipase C 2

207-751

2.30e-73

phosphoinositide phospholipase C 2

Pssm-ID: 177868 [Multi-domain] Cd Length: 581 Bit Score: 249.56 E-value: 2.30e-73

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  207 EVQELFESFSADGQkLTLLEFLDFLQEEQKERDCTSELALELIDryePSDSGKLRHVLSMDGFLSYLCskdGDIFNPACL 286
Cdd:PLN02222  26 EIKTIFEKYSENGV-MTVDHLHRFLIDVQKQDKATREDAQSIIN---SASSLLHRNGLHLDAFFKYLF---GDNNPPLAL 98

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  287 -PIYQDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPV-VYHGHTLTSRILFKDVV 364
Cdd:PLN02222  99 hEVHHDMDAPISHYFIFTGHNSYLTGNQLSSDCSEVPIIDALKKGVRVIELDIWPNSDKDDIdVLHGMTLTTPVGLIKCL 178

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  365 ATVAQYAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEqLLSTTLDGVLPTQLPSPEELRRKILVKGKKLTLEEDLE 444
Cdd:PLN02222 179 KAIRAHAFDVSDYPVVVTLEDHLTPDLQSKVAEMVTEIFGE-ILFTPPVGESLKEFPSPNSLKKRIIISTKPPKEYKEGK 257

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  445 YEEEEAEPE-------------LEESELALESQFETEPEPQEQNLQNKDKKKKSKPilcPALSSLV-------------- 497
Cdd:PLN02222 258 DDEVVQKGKdlgdeevwgrevpSFIQRNKSVDKNDSNGDDDDDDDDGEDKSKKNAP---PQYKHLIaihagkpkggitec 334

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  498 IYLKSVSFRSFTHSKEhyhfyEISSFSETKAKRLIKeagneFVQHNtwqLSRVYPSGLRTDSSNYNPQELWNAGCQMVAM 577
Cdd:PLN02222 335 LKVDPDKVRRLSLSEE-----QLEKAAEKYAKQIVR-----FTQHN---LLRIYPKGTRVTSSNYNPLVGWSHGAQMVAF 401

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  578 NMQTAGLEMDICDGHFRQNGGCGYVLKPDFLRDIQSS---FHPEKPIsPFKAqTLLIQVISGQ----QLPKVdKTKEGSI 650
Cdd:PLN02222 402 NMQGYGRSLWLMQGMFRANGGCGYIKKPDLLLKSGSDsdiFDPKATL-PVKT-TLRVTIYMGEgwyfDFRHT-HFDQYSP 478

                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  651 VDPLVKVQIFGVRLDTARQETNYVENNgFNPYWGQTLCFRVLVPELAMLRFVVMDYDWKSRNDFIGQYTLPWTCMQQGYR 730
Cdd:PLN02222 479 PDFYTRVGIAGVPGDTVMKKTKTLEDN-WIPAWDEVFEFPLTVPELALLRLEVHEYDMSEKDDFGGQTCLPVWELSQGIR 557

                        570       580
                 ....*....|....*....|.
gi 14249340  731 HIHLLSKDGISLRPASIFVYI 751
Cdd:PLN02222 558 AFPLHSRKGEKYKSVKLLVKV 578

PI-PLCc_beta1

cd08623

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

290-596

2.34e-72

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: 236.52 E-value: 2.34e-72

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 290 QDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSG--EPVVYHGHTLTSRILFKDVVATV 367
Cdd:cd08623   2 EDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGRTAeeEPVITHGFTMTTEISFKEVIEAI 81

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 368 AQYAFQTSDYPVILSLETHC-SWEQQQTMARHLTEILGEQLLSTTLDGvLPTQ----LPSPEELRRKILVKGKKltleed 442
Cdd:cd08623  82 AECAFKTSPFPILLSFENHVdSPKQQAKMAEYCRLIFGDALLMEPLEK-YPLEsgvpLPSPMDLMYKILVKNKK------ 154

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 443 leyeeeeaepeleeselalesqfetepepqeqnlqnkdkkkkskpilcpaLSSLVIYLKSVSFRSFTHSKEHYHFYEISS 522
Cdd:cd08623 155 --------------------------------------------------MSNLVNYIQPVKFESFEASKKRNKSFEMSS 184

                       250       260       270       280       290       300       310
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 14249340 523 FSETKAKRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQN 596
Cdd:cd08623 185 FVETKGLEQLTKSPVEFVEYNKMQLSRIYPKGTRVDSSNYMPQLFWNAGCQMVALNFQTVDLSMQINMGMYEYN 258

PLN02230

phosphoinositide phospholipase C 4

206-740

6.74e-67

phosphoinositide phospholipase C 4

Pssm-ID: 177875 [Multi-domain] Cd Length: 598 Bit Score: 232.67 E-value: 6.74e-67

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  206 AEVQELFESFsADGQKLTLLEFLDFLQEEqkERDCTSELALELIDRYEPSDSGKLRHV-------LSMDGFLSYLCSKDg 278
Cdd:PLN02230  29 ADVRDLFEKY-ADGDAHMSPEQLQKLMAE--EGGGEGETSLEEAERIVDEVLRRKHHIakftrrnLTLDDFNYYLFSTD- 104

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  279 dIFNPACLPIYQDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRI 358
Cdd:PLN02230 105 -LNPPIADQVHQNMDAPLSHYFIFTGHNSYLTGNQLSSNCSELPIADALRRGVRVVELDLWPRGTDDVCVKHGRTLTKEV 183

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  359 LFKDVVATVAQYAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTtlDGVLPTQLPSPEELRRKILVKGKKLT 438
Cdd:PLN02230 184 KLGKCLDSIKANAFAISKYPVIITLEDHLTPKLQFKVAKMITQTFGDMLYYH--DSEGCQEFPSPEELKEKILISTKPPK 261

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  439 LEEDLEYEEEEAEPELEESELALEsqFETEPE---PQEQNLQ------NKDKKKKSKPILCPALSSLVIYLKSVSFRSFT 509
Cdd:PLN02230 262 EYLEANDAKEKDNGEKGKDSDEDV--WGKEPEdliSTQSDLDkvtssvNDLNQDDEERGSCESDTSCQLQAPEYKRLIAI 339

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  510 HSKEHYHFYEIS-----------SFSETKAKRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMN 578
Cdd:PLN02230 340 HAGKPKGGLRMAlkvdpnkirrlSLSEQLLEKAVASYGADVIRFTQKNFLRIYPKGTRFNSSNYKPQIGWMSGAQMIAFN 419

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  579 MQTAGLEMDICDGHFRQNGGCGYVLKPDFLRDIQSS---FHPEKPISPFKaqTLLIQVISGQQ-LPKVDKTKEGSIVDP- 653
Cdd:PLN02230 420 MQGYGRALWLMEGMFRANGGCGYVKKPDFLMDAGPNgqdFYPKDNSCPKK--TLKVKVCMGDGwLLDFKKTHFDSYSPPd 497

                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  654 -LVKVQIFGVRLDTARQETNyVENNGFNPYWGQTLCFRVLVPELAMLRFVVMDYDWKSRNDFIGQYTLPWTCMQQGYRHI 732
Cdd:PLN02230 498 fFVRVGIAGAPVDEVMEKTK-IEYDTWTPIWNKEFIFPLAVPELALLRVEVHEHDINEKDDFGGQTCLPVSEIRQGIHAV 576


                 ....*...
gi 14249340  733 HLLSKDGI 740
Cdd:PLN02230 577 PLFNRKGV 584

PLCXc

smart00148

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

292-435

2.13e-66

Pssm-ID: 197543 [Multi-domain] Cd Length: 143 Bit Score: 216.38 E-value: 2.13e-66

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340    292 MTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRILFKDVVATVAQYA 371
Cdd:smart00148   1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 14249340    372 FQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDGVLpTQLPSPEELRRKILVKGK 435
Cdd:smart00148  81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSL-EVLPSPEQLRGKILLKVR 143

PI-PLCc

cd00137

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

289-596

2.37e-66

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: 220.98 E-value: 2.37e-66

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 289 YQDMTQPLNHYFICSSHNTYLVGDQL-----CGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTsRILFKDV 363
Cdd:cd00137   1 HHPDTQPLAHYSIPGTHDTYLTAGQFtikqvWGLTQTEMYRQQLLSGCRCVDIRCWDGKPEEPIIYHGPTFL-DIFLKEV 79

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 364 VATVAQYAFQTSDYPVILSLETHCS--WEQQQTMARHLTEILGEqLLSTTLDGVlPTQLPSPEELRRKILVKGKKltlee 441
Cdd:cd00137  80 IEAIAQFLKKNPPETIIMSLKNEVDsmDSFQAKMAEYCRTIFGD-MLLTPPLKP-TVPLPSLEDLRGKILLLNKK----- 152

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 442 dleyeeeeaepeleeselaleSQFetepepqeqnlqnkdkkkkskpilcpalSSLVIYLKSVSFRSFTHSKEHYHFYEIS 521
Cdd:cd00137 153 ---------------------NGF----------------------------SGPTGSSNDTGFVSFEFSTQKNRSYNIS 183

                       250       260       270       280       290       300       310       320
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 522 SFSETKA----KRLIKEAGNEFVQHNTWQLSRVYPSGLR---------TDSSNYNPQELWN---AGCQMVAMNMQTAGLE 585
Cdd:cd00137 184 SQDEYKAyddeKVKLIKATVQFVDYNKNQLSRNYPSGTSggtawyyyaMDSNNYMPQMFWNanpAGCGIVILDFQTMDLP 263

                       330
                ....*....|.
gi 14249340 586 MDICDGHFRQN 596
Cdd:cd00137 264 MQQYMAVIEFN 274

PI-PLCc_plant

cd08599

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

289-596

5.87e-64

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: 213.00 E-value: 5.87e-64

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 289 YQDMTQPLNHYFICSSHNTYLVGDQLCGQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRILFKDVVATVA 368
Cdd:cd08599   1 HHDMTAPLSHYFIFSSHNSYLTGNQLSSRSSTAPIIEALLRGCRVIELDLWPGGRGDICVLHGGTLTKPVKFEDCIKAIK 80

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 369 QYAFQTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDgVLPTQLPSPEELRRKILVKgkkltleedleyeee 448
Cdd:cd08599  81 ENAFTASEYPVIITLENHLSPELQAKAAQILRETLGDKLFYPDSE-DLPEEFPSPEELKGKILIS--------------- 144

                       170       180       190       200       210       220       230       240
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 449 eaepeleeselalesqfeTEPePQEQNlqnkdkkkkskpilcpalsslviylksvsfrsfthskehyhfyeisSFSETKA 528
Cdd:cd08599 145 ------------------DKP-PVIRN----------------------------------------------SLSETQL 159

                       250       260       270       280       290       300
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 14249340 529 KRLI-KEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQN 596
Cdd:cd08599 160 KKVIeGEHPTDLIEFTQKNLLRVYPAGLRITSSNYDPMLAWMHGAQMVALNMQGYDRPLWLNRGKFRAN 228

EFh_PI-PLCdelta

cd16202

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

138-277

7.15e-64

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: 209.39 E-value: 7.15e-64

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 138 WLSDWFQRGDKNQDGKMSFQEVQRLLHLMNVEMDQEYAFSLFQAADTSQSGTLEGEEFVQFYKALTKRAEVQELFESFSA 217
Cdd:cd16202   1 WLKDQFRKADKNGDGKLSFKECKKLLKKLNVKVDKDYAKKLFQEADTSGEDVLDEEEFVQFYNRLTKRPEIEELFKKYSG 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 218 DGQKLTLLEFLDFLQEEQKERDCTSELALELIDRYEPSDSGKLRHVLSMDGFLSYLCSKD 277
Cdd:cd16202  81 DDEALTVEELRRFLQEEQKVKDVTLEWAEQLIETYEPSEDLKAQGLMSLDGFTLFLLSPD 140

PI-PLC-Y

pfam00387

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

493-607

2.09e-63

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

Pssm-ID: 459794 Cd Length: 114 Bit Score: 206.93 E-value: 2.09e-63

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340   493 LSSLVIYLKSVSFRSFTHsKEHYHFYEISSFSETKAKRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGC 572
Cdd:pfam00387   1 LSDLVVYTQSVKFKSFST-PESKTPNHIFSFSESKALKLIKSSSAAFVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNCGV 79

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 14249340   573 QMVAMNMQTAGLEMDICDGHFRQNGGCGYVLKPDF 607
Cdd:pfam00387  80 QMVALNWQTPDEGMQLNEGMFADNGGCGYVLKPEF 114

PLCYc

smart00149

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

494-608

1.77e-62

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: 204.78 E-value: 1.77e-62

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340    494 SSLVIYLKSVSFRSFTHSKEHYHFYEISSFSETKAKRLIKEAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQELWNAGCQ 573
Cdd:smart00149   1 SDLVIYCAPVKFRSFESAESKNPFYEMSSFSETKAKKLLKKSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGCQ 80

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 14249340    574 MVAMNMQTAGLEMDICDGHFRQNGGCGYVLKPDFL 608
Cdd:smart00149  81 MVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115

PH_PLC_delta

cd13363

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

18-133

3.47e-60

Pssm-ID: 270169 Cd Length: 117 Bit Score: 198.70 E-value: 3.47e-60

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  18 MQEGMPMRKVRSKSWKKLRYFRLQNDGMTVWHARQ-ARGSAKPSFSISDVETIRNGHDSELLRSLAEELPLEQGFTIVFH 96
Cdd:cd13363   1 LLQGSPLLKVRSRSWKKERFYKLQEDCKTVWHESKkTRSNSKQTFSIEDIESVREGHQSEGLRKYAEAFPEDRCFSIVFK 80

                        90       100       110
                ....*....|....*....|....*....|....*..
gi 14249340  97 GRRSNLDLMANSVEEAQIWMRGLQLLVDLVTSMDHQE 133
Cdd:cd13363  81 GRRKNLDLIAPSEEEAQRWVRGLEKLIARLTNMSQRE 117

C2_PLC_like

cd00275

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

626-751

1.29e-51

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 175.81 E-value: 1.29e-51

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 626 AQTLLIQVISGQQLPKvDKTKEGSIVDPLVKVQIFGV-RLDTARQETNYVENNGFNPYWGQTLCFRVLVPELAMLRFVVM 704
Cdd:cd00275   1 PLTLTIKIISGQQLPK-PKGDKGSIVDPYVEVEIHGLpADDSAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVY 79

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*..
gi 14249340 705 DYDwKSRNDFIGQYTLPWTCMQQGYRHIHLLSKDGISLRPASIFVYI 751
Cdd:cd00275  80 DED-SGDDDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHI 125

PLN02223

phosphoinositide phospholipase C

223-739

9.29e-44

phosphoinositide phospholipase C

Pssm-ID: 165867 [Multi-domain] Cd Length: 537 Bit Score: 166.35 E-value: 9.29e-44

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  223 TLLEFLDFlqeeQKERDCTSELALELIDR---YEPSDSGKLRH--VLSMDGFLSYLCSKDgdiFNPaclPI-----YQDM 292
Cdd:PLN02223  39 RFIELLDT----EKDEDGAGLNAAEKIAAelkRRKCDILAFRNlrCLELDHLNEFLFSTE---LNP---PIgdqvrHHDM 108

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  293 TQPLNHYFICSSHNTYLVGDQLCGQS-SVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLTSRILFKDVVATVAQYA 371
Cdd:PLN02223 109 HAPLSHYFIHTSLKSYFTGNNVFGKLySIEPIIDALEQGVRVVELDLLPDGKDGICVRPKWNFEKPLELQECLDAIKEHA 188

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  372 F-QTSDYPVILSLETHCSWEQQQTMARHLTEILGEQLLSTTLDGVLpTQLPSPEELRRKILVKGKKLTLEEDLEYEEEEA 450
Cdd:PLN02223 189 FtKCRSYPLIITFKDGLKPDLQSKATQMIDQTFGDMVYHEDPQHSL-EEFPSPAELQNKILISRRPPKELLYAKADDGGV 267

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  451 EPEleeselaleSQFETEPEPQEQNLQNKDKKKKSKP--ILCPALSSLVIYLKsvsfrsfthsKEHYHFYEISSFSETKA 528
Cdd:PLN02223 268 GVR---------NELEIQEGPADKNYQSLVGFHAVEPrgMLQKALTGKADDIQ----------QPGWYERDIISFTQKKF 328

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  529 KRLIKEAGNEFVqhntwqlsrvYPSglrtdssnYNPQELWNAGCQMVAMNMQTAGLEMDICDGHFRQNGGCGYVLKPDFL 608
Cdd:PLN02223 329 LRTRPKKKNLLI----------NAP--------YKPQRAWMHGAQLIALSRKDDKEKLWLMQGMFRANGGCGYVKKPDFL 390

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  609 RDIQSS--FHPEkpISPFKAQTLLIQVISGQQLPKVDKTKEGSIVDP--LVKVQIFGVRLDTARQETNyVENNGFNPYWG 684
Cdd:PLN02223 391 LNAGPSgvFYPT--ENPVVVKILKVKIYMGDGWIVDFKKRIGRLSKPdlYVRISIAGVPHDEKIMKTT-VKNNEWKPTWG 467

                        490       500       510       520       530
                 ....*....|....*....|....*....|....*....|....*....|....*
gi 14249340  685 QTLCFRVLVPELAMLRFVVMDYDWKSRNDFIGQYTLPWTCMQQGYRHIHLLSKDG 739
Cdd:PLN02223 468 EEFTFPLTYPDLALISFEVYDYEVSTADAFCGQTCLPVSELIEGIRAVPLYDERG 522

EF-hand_like

pfam09279

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

198-282

1.64e-42

Pssm-ID: 401279 [Multi-domain] Cd Length: 85 Bit Score: 148.93 E-value: 1.64e-42

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340   198 FYKALTKRAEVQELFESFSADGQKLTLLEFLDFLQEEQKERDCTSELALELIDRYEPSDSGKLRHVLSMDGFLSYLCSKD 277
Cdd:pfam09279   1 FYKMLTQREEIDEIFQEYSGDGQKLSLDELVDFLREEQREEDASPALALSLIERYEPSETAKKQHAMTKDGFLMYLCSPD 80


                  ....*
gi 14249340   278 GDIFN 282
Cdd:pfam09279  81 GSIFN 85

EFh_PI-PLCdelta1

cd16217

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

138-277

1.92e-39

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: 142.18 E-value: 1.92e-39

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 138 WLSDWFQRGDKNQDGKMSFQEVQRLLHLMNVEMDQEYAFSLFQAADTSQSGTLEGEEFVQFYKALTKRAEVQELFESFSA 217
Cdd:cd16217   1 WIHSCLRKADKNKDNKMSFKELKDFLKEINIEVDDDYAEKLFKECDKSKSGFLEGEEIEEFYKLLTKREEIDVIFGEYAK 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 218 DGQKLTLLEFLDFLQEEQKERDcTSELALELIDRYEPSDSGKLRHVLSMDGFLSYLCSKD 277
Cdd:cd16217  81 SDGTMSRNNLLNFLQEEQREEV-APAYALSLIEKYEPDETAKAQRQMTKDGFLMYLLSPE 139

EFh_PI-PLC

cd15898

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

138-277

5.24e-36

Pssm-ID: 320029 [Multi-domain] Cd Length: 137 Bit Score: 132.41 E-value: 5.24e-36

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 138 WLSDWFQRGDKNQDGKMSFQEVQRLLHLMNVEMDQEYAFSLFQAADTSQSGTLEGEEFVQFYKALTKRAEVQELFESFSA 217
Cdd:cd15898   1 WLRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVDTNGDGTLTFDEFEELYKSLTERPELEPIFKKYAG 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 14249340 218 DGQK-LTLLEFLDFLQEEQKErDCTSELALELIDRYEPSDSgklRHVLSMDGFLSYLCSKD 277
Cdd:cd15898  81 TNRDyMTLEEFIRFLREEQGE-NVSEEECEELIEKYEPERE---NRQLSFEGFTNFLLSPE 137

EFh_PI-PLCeta

cd16205

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

138-277

5.10e-34

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: 127.11 E-value: 5.10e-34

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 138 WLSDWFQRGDKNQDGKMSFQEVQRLLHLMNVEMDQEYAFSLFQAADTSQS-GTLEGEEFVQFYKALTKRAEVQELFESFS 216
Cdd:cd16205   1 WLKQTFEEADKNGDGLLSIGEILQLMHKLNVNLPRRKVRQMFKEADTDDNqGTLDFEEFCAFYKMMSTRRELYLLLLSYS 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 14249340 217 ADGQKLTLLEFLDFLQEEQKERDCTSELALELIDRYEPSDSGKLRHVLSMDGFLSYLCSKD 277
Cdd:cd16205  81 NKKDYLTLEDLARFLEVEQKMTNVTLEYCLDIIEKFEPSEENKKNGLLGIDGFTNYMRSPA 141

EFh_PI-PLCdelta3

cd16218

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

138-277

1.99e-33

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: 125.24 E-value: 1.99e-33

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 138 WLSDWFQRGDKNQDGKMSFQEVQRLLHLMNVEMDQEYAFSLFQAADTSQSGTLEGEEFVQFYKALTKRAEVQELFESFSA 217
Cdd:cd16218   1 WIHEYLRRADLNKDGKMSFEEIKDLLQMINIDLNEQYAYQLFKECDRSNDDRLEEHEIEEFCRRLMQRPELEEIFHQYSG 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 218 DGQKLTLLEFLDFLQeEQKErDCTSELALELIDRYEPSDSGKLRHVLSMDGFLSYLCSKD 277
Cdd:cd16218  81 EDCVLSAEELREFLK-DQGE-DASLVHAKELIQTYELNEKAKQHQLMTLDGFTMYMLSKD 138

EFh_PI-PLCeta1

cd16220

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

138-275

2.20e-26

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: 105.11 E-value: 2.20e-26

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 138 WLSDWFQRGDKNQDGKMSFQEVQRLLHLMNVEMDQEYAFSLFQAADTSQS-GTLEGEEFVQFYKALTKRAEVQELFESFS 216
Cdd:cd16220   1 WVKQTFEEADKNGDGLLNIEEIYQLMHKLNVNLPRRKVRQMFQEADTDENqGTLTFEEFCVFYKMMSLRRDLYLLLLSYS 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 14249340 217 ADGQKLTLLEFLDFLQEEQKERDCTSELALELIDRYEPSDSGKLRHVLSMDGFLSYLCS 275
Cdd:cd16220  81 DKKDHLTVEELAQFLKVEQKMNNVTTEYCLDIIKKFEVSEENKEQNVLGIEGFTNFMRS 139

EFh_ScPlc1p_like

cd16207

EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar ...

145-277

3.01e-24

EF-hand motif found in Saccharomyces cerevisiae phospholipase C-1 (ScPlc1p) and similar proteins; This family represents a group of putative phosphoinositide-specific phospholipase C (PI-PLC, EC 3.1.4.11) encoded by PLC1 genes from yeasts, which are homologs of the delta isoforms of mammalian PI-PLC in terms of overall sequence similarity and domain organization. Mammalian PI-PLC is a signaling enzyme that hydrolyzes the membrane phospholipids phosphatidylinositol-4,5-bisphosphate (PIP2) to generate two important second messengers in eukaryotic signal transduction cascades, inositol 1,4,5-trisphosphate (InsP3) and diacylglycerol (DAG). InsP3 triggers inflow of calcium from intracellular stores, while DAG, together with calcium, activates protein kinase C, which then phosphorylates other molecules, leading to altered cellular activity. Calcium is required for the catalysis. The prototype of this family is protein Plc1p (also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase 1) encoded by PLC1 genes from Saccharomyces cerevisiae. ScPlc1p contains both highly conserved X- and Y- regions of PLC catalytic core domain, as well as a presumptive EF-hand like calcium binding motif. Experiments show that ScPlc1p displays calcium dependent catalytic properties with high similarity to those of the mammalian PLCs, and plays multiple roles in modulating the membrane/protein interactions in filamentation control. CaPlc1p encoded by CAPLC1 from the closely related yeast Candida albicans, an orthologue of S. cerevisiae Plc1p, is also included in this group. Like SCPlc1p, CaPlc1p has conserved presumptive catalytic domain, shows PLC activity when expressed in E. coli, and is involved in multiple cellular processes. There are two other gene copies of CAPLC1 in C. albicans, CAPLC2 (also named as PIPLC) and CAPLC3. Experiments show CaPlc1p is the only enzyme in C. albicans which functions as PLC. The biological functions of CAPLC2 and CAPLC3 gene products must be clearly different from CaPlc1p, but their exact roles remain unclear. Moreover, CAPLC2 and CAPLC3 gene products are more similar to extracellular bacterial PI-PLC than to the eukaryotic PI-PLC, and they are not included in this subfamily.

Pssm-ID: 320037 [Multi-domain] Cd Length: 142 Bit Score: 98.86 E-value: 3.01e-24

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 145 RGDKNQDGKMSFQEVQRLLHLMNVEMDQEYAFSLFQAADTSQSGTLEGEEFVQFYKALTKRAEVQELFESFSADGQ-KLT 223
Cdd:cd16207  10 SKKQDGDERLDFEDVEKLCRRLHINCSESYLRELFDKADTDKKGYLNFEEFQEFVKLLKRRKDIKAIFKQLTKPGSdGLT 89

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....
gi 14249340 224 LLEFLDFLQEEQKERDCTSELAlELIDRYEPSDSGKLRHVLSMDGFLSYLCSKD 277
Cdd:cd16207  90 LEEFLKFLRDVQKEDVDRETWE-KIFEKFARRIDDSDSLTMTLEGFTSFLLSSY 142

smart00239

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

628-734

5.50e-24

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 96.79 E-value: 5.50e-24

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340    628 TLLIQVISGQQLPKVDKtkeGSIVDPLVKVQIFGVRLDTARqeTNYVENNGfNPYWGQTLCFRVLVPELAMLRFVVMDYD 707
Cdd:smart00239   1 TLTVKIISARNLPPKDK---GGKSDPYVKVSLDGDPKEKKK--TKVVKNTL-NPVWNETFEFEVPPPELAELEIEVYDKD 74

                           90       100
                   ....*....|....*....|....*..
gi 14249340    708 WKSRNDFIGQYTLPWTCMQQGYRHIHL 734
Cdd:smart00239  75 RFGRDDFIGQVTIPLSDLLLGGRHEKL 101

PI-PLCc_GDPD_SF

cd08555

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

303-408

1.56e-23

Pssm-ID: 176498 [Multi-domain] Cd Length: 179 Bit Score: 98.28 E-value: 1.56e-23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 303 SSHNTYLVGDQlcgQSSVEGYIRALKRGCRCVEVDVWDGPSGEPVVYHGHTLT------SRILFKDVVATVAQYAFqTSD 376
Cdd:cd08555   2 LSHRGYSQNGQ---ENTLEAFYRALDAGARGLELDVRLTKDGELVVYHGPTLDrttagiLPPTLEEVLELIADYLK-NPD 77

                        90       100       110
                ....*....|....*....|....*....|....*.
gi 14249340 377 YPVILSLETHCSW----EQQQTMARHLTEILGEQLL 408
Cdd:cd08555  78 YTIILSLEIKQDSpeydEFLAKVLKELRVYFDYDLR 113

EFh_PI-PLCeta2

cd16221

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

138-275

1.56e-23

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: 96.92 E-value: 1.56e-23

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 138 WLSDWFQRGDKNQDGKMSFQEVQRLLHLMNVEMDQEYAFSLFQAADTS-QSGTLEGEEFVQFYKALTKRAEVQELFESFS 216
Cdd:cd16221   1 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEADTDdNQGTLGFEEFCAFYKMMSTRRDLYLLMLTYS 80

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*....
gi 14249340 217 ADGQKLTLLEFLDFLQEEQKERDCTSELALELIDRYEPSDSGKLRHVLSMDGFLSYLCS 275
Cdd:cd16221  81 NHKDHLDTNDLQRFLEVEQKMAGVTREHCLEIISQFEPCSENKQNGALGIDGFTNYMRS 139

EFh_PRIP

cd16206

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

138-277

2.63e-21

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: 90.73 E-value: 2.63e-21

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 138 WLSDWFQRGDKNQDGKMSFQEVQRLLHLMNVEMDQ---EYAFSLFQAADTSQSGTLEGEEFVQFYKALTKRAEVQELFES 214
Cdd:cd16206   1 WLESVFEEADTNKSGFLDEEEAVQLIKQLNPGLSTsriKQKLKELQKKKDGARGRVSSDEFVELFKELATRPEIYFLLVR 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 14249340 215 FSADGQKLTLLEFLDFLQEEQKERDCTSELALELIDRYEPSDSGKLRHVLSMDGFLSYLCSKD 277
Cdd:cd16206  81 YASNKDYLTVDDLMLFLEAEQGMTGVTKEKCLEIINKYEPSEEGREKGQLGIDGFTRYLLSEE 143

EF-hand_10

pfam14788

EF hand;

153-202

9.98e-21

EF hand;

Pssm-ID: 405477 Cd Length: 50 Bit Score: 85.93 E-value: 9.98e-21

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 14249340   153 KMSFQEVQRLLHLMNVEMDQEYAFSLFQAADTSQSGTLEGEEFVQFYKAL 202
Cdd:pfam14788   1 KMSFKELKNFLRLINIEVDDSYARKLFQKCDTSQSGRLEGEEIEEFYKLL 50

EFh_PI-PLCzeta

cd16204

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

147-277

1.55e-20

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: 88.33 E-value: 1.55e-20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 147 DKNQDGKMSFQEVQRLLHLMNVEMDQEYAFSLFQAADTSQSGTLEGEEFVQFYKALTKRAEVQELFESFSADGQKLTLLE 226
Cdd:cd16204  12 DRFRKGKINLESTLKLLEKLDIPFDYIHVKYIFKKNDSFKAGNITIEDFRAIYRAIAHRCEIHEIFNTYSENRKILSAPN 91

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|.
gi 14249340 227 FLDFLQEEQKERDCTSELALELIDRYEPSDSGKLRHVLSMDGFLSYLCSKD 277
Cdd:cd16204  92 LVGFLKKEQFQDEADETIASELIAKYEPIEEVRKRKQMSFEGFIRYMTSED 142

pfam00168

C2 domain;

627-733

6.38e-20

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 85.45 E-value: 6.38e-20

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340   627 QTLLIQVISGQQLPKVDKTkegSIVDPLVKVQIFGvrlDTARQETNYVENNgFNPYWGQTLCFRVLVPELAMLRFVVMDY 706
Cdd:pfam00168   1 GRLTVTVIEAKNLPPKDGN---GTSDPYVKVYLLD---GKQKKKTKVVKNT-LNPVWNETFTFSVPDPENAVLEIEVYDY 73

                          90       100
                  ....*....|....*....|....*..
gi 14249340   707 DWKSRNDFIGQYTLPWTCMQQGYRHIH 733
Cdd:pfam00168  74 DRFGRDDFIGEVRIPLSELDSGEGLDG 100

PH_PLC_ELMO1

cd01248

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

18-123

7.94e-20

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: 85.07 E-value: 7.94e-20

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  18 MQEGMPMRKVRSKSWKKLRYFRLQNDGMTVWHARQARGSAKPSFSISDVETIRNGHDSELLRS--LAEELPLEQGFTIVF 95
Cdd:cd01248   1 LQQGTLLLKYREGSKPKERTFYLDPDGTRITWESSKKKSEKKSIDISDIKEIRPGKDTDGFKRkkKSNKPKEERCFSIIY 80

                        90       100
                ....*....|....*....|....*...
gi 14249340  96 HGRRSNLDLMANSVEEAQIWMRGLQLLV 123
Cdd:cd01248  81 GSNNKTLDLVAPSEDEANLWVEGLRALL 108

EFh_PI-PLC21

cd16213

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

193-277

3.83e-16

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: 76.19 E-value: 3.83e-16

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 193 EEFVQFYKALTKRAEVQELFESFSADGQK-LTLLEFLDFLQEEQkeRD----------CTSELALELIDRYEPSDSGKLR 261
Cdd:cd16213  61 EDFFNFYRRLTGRQEVEKIFDELGAKKKPyLTTEQFVDFLNKTQ--RDprlneilypyANPKRARDLINQYEPNKSFAKK 138

                        90
                ....*....|....*.
gi 14249340 262 HVLSMDGFLSYLCSKD 277
Cdd:cd16213 139 GHLSVEGFLRYLMSED 154

EFh_PI-PLCbeta

cd16200

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

193-277

1.42e-15

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: 74.59 E-value: 1.42e-15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 193 EEFVQFYKALTKRAEVQELFESFSADG-QKLTLLEFLDFLQEEQkeRD----------CTSELALELIDRYEPSDSGKLR 261
Cdd:cd16200  60 EKFFKLYNKLCPRPDIDEIFKELGGKRkPYLTLEQLVDFLNEEQ--RDprlneilfpfHTKEQAKKLIDKYEPNEKNKKK 137

                        90
                ....*....|....*.
gi 14249340 262 HVLSMDGFLSYLCSKD 277
Cdd:cd16200 138 GQLTLEGFLRYLMSDE 153

EFh_PRIP2

cd16223

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

138-277

1.66e-15

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: 74.17 E-value: 1.66e-15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 138 WLSDWFQRGDKNQDGKMSFQEVQRLLHLMNVEMDQ---EYAFSLFQAADTSQSGTLEGEEFVQFYKALTKRAEVQELFES 214
Cdd:cd16223   1 WLSQMFVEADTDNVGHITLCRAVQFIKNLNPGLKTskiELKFKELHKSKEKGGTEVTKEEFIEVFHELCTRPEIYFLLVQ 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 14249340 215 FSADGQKLTLLEFLDFLQEEQKERDCTSELALELIDRYEPSDSGKLRHVLSMDGFLSYLCSKD 277
Cdd:cd16223  81 FSSNKEFLDTKDLMMFLEAEQGMAHVTEEISLDIIHKYEPSKEGQEKGWLSLDGFTNYLMSPE 143

PH_PLC_eta

cd13364

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

18-124

3.01e-15

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: 72.31 E-value: 3.01e-15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  18 MQEGMPMRKVRSKSWKKLRYFRLQNDGMTV-WHARQaRGSAKPSFSISDVETIRNGHDSELLRS--LAEELPLEQGFTIV 94
Cdd:cd13364   1 MQEGSELVKVRSNSRQYRRFFYLDEDKSSIrWKPSK-KKSEKAKIPISSIREVREGKTTDIFRScdISGDFPEECCFSII 79

                        90       100       110
                ....*....|....*....|....*....|
gi 14249340  95 FHGRRSNLDLMANSVEEAQIWMRGLQLLVD 124
Cdd:cd13364  80 YGEEYETLDLVASSPDEANIWITGLRYLMS 109

cd00030

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

629-721

5.89e-15

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

Pssm-ID: 175973 [Multi-domain] Cd Length: 102 Bit Score: 71.33 E-value: 5.89e-15

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 629 LLIQVISGQQLPKVDKtkeGSIVDPLVKVQIFGVRldtaRQETNYVENNgFNPYWGQTLCFRVLVPELAMLRFVVMDYDW 708
Cdd:cd00030   1 LRVTVIEARNLPAKDL---NGKSDPYVKVSLGGKQ----KFKTKVVKNT-LNPVWNETFEFPVLDPESDTLTVEVWDKDR 72

                        90
                ....*....|...
gi 14249340 709 KSRNDFIGQYTLP 721
Cdd:cd00030  73 FSKDDFLGEVEIP 85

FRQ1

COG5126

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

126-233

1.50e-12

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

Pssm-ID: 444056 [Multi-domain] Cd Length: 137 Bit Score: 65.58 E-value: 1.50e-12

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 126 VTSMDHQERLDQWLSDWFQRGDKNQDGKMSFQEVQRLLHLMNVEMDQEYAFSLFQAADTSQSGTLEGEEFVQFYKAL-TK 204
Cdd:COG5126  22 LERDDFEALFRRLWATLFSEADTDGDGRISREEFVAGMESLFEATVEPFARAAFDLLDTDGDGKISADEFRRLLTALgVS 101

                        90       100       110
                ....*....|....*....|....*....|
gi 14249340 205 RAEVQELFESFSADGQ-KLTLLEFLDFLQE 233
Cdd:COG5126 102 EEEADELFARLDTDGDgKISFEEFVAAVRD 131

EFh_PRIP1

cd16222

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

138-277

1.00e-11

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: 63.34 E-value: 1.00e-11

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 138 WLSDWFQRGDKNQDGKMSFQEVQRLLHLMNVEMDQ---EYAFSLFQAADTSQSGTLEGEEFVQFYKALTKRAEVQELFES 214
Cdd:cd16222   1 WLSAVFEAADVDGYGIMLEDTAVELIKQLNPGIKEakiRLKFKEIQKSKEKLTTRVTEEEFCEAYSELCTRPEVYFLLVQ 80

                        90       100       110       120       130       140
                ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 14249340 215 FSADGQKLTLLEFLDFLQEEQKERDCTSELALELIDRYEPSDSGKLRHVLSMDGFLSYLCSKD 277
Cdd:cd16222  81 ISKNKEYLDAKDLMLFLEAEQGMTHITEEMCLDIIRRYEPSQEGRLKGFLGIDGFTQYLLSSE 143

EFh_PI-PLCgamma

cd16201

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

138-277

4.08e-09

EF-hand motif found in phosphoinositide phospholipase C gamma isozymes (PI-PLC-gamma); PI-PLC-gamma isozymes represent a class of metazoan PI-PLCs that hydrolyze the membrane lipid phosphatidylinositol 4,5-bisphosphate (PIP2) to propagate diverse intracellular responses that underlie the physiological action of many hormones, neurotransmitters, and growth factors. They can form a complex with the phosphorylated cytoplasmic domains of the immunoglobulin Ig-alpha and Ig-beta subunits of the B cell receptor (BCR), the membrane-tethered Src family kinase Lyn, phosphorylated spleen tyrosine kinase (Syk), the phosphorylated adaptor protein B-cell linker (BLNK), and activated Bruton's tyrosine kinase (Btk). Like other PI-PLC isozymes, PI-PLC-gamma isozymes contain a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. Unique to PI-PLC-gamma, a second PH domain, which is split by two SH2 (Src homology 2) domains, and one SH3 (Src homology 3) domain, are present within this linker. The SH2 and SH3 domains are responsible for the binding of phosphotyrosine-containing sequences and proline-rich sequences, respectively. There are two PI-PLC-gamma isozymes (1-2), both of which are activated by receptor and non-receptor tyrosine kinases due to the presence of SH2 and SH3 domains.

Pssm-ID: 320031 [Multi-domain] Cd Length: 145 Bit Score: 55.66 E-value: 4.08e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 138 WLSDWFQRGDKNQDGKMSFQEVQRLLHLMNVEMDQEYAFSLFQAADTSQSGTLEGEEFVQFYKALT-KRAEVQELFESF- 215
Cdd:cd16201   1 WLRKEFYSMDRTRRETVTLKDLKAFLPRVNCKISTNKLREKFQEVDTRRRGELGFDDFAQLYHKLMfDQKIIEDFFKKYs 80

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 14249340 216 -SADGQKLTLLEFLDFLQEEQKERDCTSELAL-ELI---------DRYEPSdsgklrhvLSMDGFLSYLCSKD 277
Cdd:cd16201  81 ySSDGQTVTLEDFQRFLLEEQKEPWANDPNAVrEFMrdflqdplrDVQEPY--------FTLDEFLDYLFSKE 145

FRQ1

COG5126

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

139-260

6.70e-09

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

Pssm-ID: 444056 [Multi-domain] Cd Length: 137 Bit Score: 54.80 E-value: 6.70e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 139 LSDWFQRGDKNQDGKMSFQEVQRLLHLMNVEmdqeyafsLFQAADTSQSGTLEGEEFVQFYKAL---TKRAEVQELFESF 215
Cdd:COG5126   7 LDRRFDLLDADGDGVLERDDFEALFRRLWAT--------LFSEADTDGDGRISREEFVAGMESLfeaTVEPFARAAFDLL 78

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 14249340 216 SADG-QKLTLLEFLDFLqeeqKERDCTSELALELIDRYEPSDSGKL 260
Cdd:COG5126  79 DTDGdGKISADEFRRLL----TALGVSEEEADELFARLDTDGDGKI 120

EFh_NorpA_like

cd16212

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

193-277

9.93e-09

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: 54.86 E-value: 9.93e-09

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 193 EEFVQFYKALTKRAEVQELFESFS-ADGQKLTLLEFLDFLQEEQKERDCTSEL--------ALELIDRYEPSDSGKLRHV 263
Cdd:cd16212  60 EKFYALYHKICPRNDIEELFTSITkGKGEHISLAQLINFMNDKQRDPRLNEILyplydekrCTEIIKAYEQNEENIKNKR 139

                        90
                ....*....|....
gi 14249340 264 LSMDGFLSYLCSKD 277
Cdd:cd16212 140 MSKDGFIRYLMSDE 153

C2B_Synaptotagmin

cd00276

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

614-731

1.14e-08

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: 54.13 E-value: 1.14e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 614 SFHPEkpispfkAQTLLIQVISGQQLPKVDktkEGSIVDPLVKVQIF--GVRLDTARqeTNyVENNGFNPYWGQTLCFRV 691
Cdd:cd00276   8 SYLPT-------AERLTVVVLKARNLPPSD---GKGLSDPYVKVSLLqgGKKLKKKK--TS-VKKGTLNPVFNEAFSFDV 74

                        90       100       110       120
                ....*....|....*....|....*....|....*....|..
gi 14249340 692 LVPELAM--LRFVVMDYDWKSRNDFIGQYTLPWTCMQQGYRH 731
Cdd:cd00276  75 PAEQLEEvsLVITVVDKDSVGRNEVIGQVVLGPDSGGEELEH 116

smart00233

Pleckstrin homology domain; Domain commonly found in eukaryotic signalling proteins. The ...

26-124

1.78e-08

Pssm-ID: 214574 [Multi-domain] Cd Length: 102 Bit Score: 52.55 E-value: 1.78e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340     26 KVRSKSWKKlRYFRLQNDGMTVWHARQARGSAKPSFSIS-DVETIRNGHDSEllrslaeELPLEQGFTIVfHGRRSNLDL 104
Cdd:smart00233  12 GGGKKSWKK-RYFVLFNSTLLYYKSKKDKKSYKPKGSIDlSGCTVREAPDPD-------SSKKPHCFEIK-TSDRKTLLL 82

                           90       100
                   ....*....|....*....|
gi 14249340    105 MANSVEEAQIWMRGLQLLVD 124
Cdd:smart00233  83 QAESEEEREKWVEALRKAIA 102

C2A_Synaptotagmin-7

cd08386

C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...

624-721

3.09e-08

C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176032 [Multi-domain] Cd Length: 125 Bit Score: 52.72 E-value: 3.09e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 624 FKAQTLLIQVISGQQLPKVDKTkeGSIvDPLVKVQIFGvrlDTARQETNYVENNGFNPYWGQTLCFRVLVPELAMLRFV- 702
Cdd:cd08386  13 FQESTLTLKILKAVELPAKDFS--GTS-DPFVKIYLLP---DKKHKLETKVKRKNLNPHWNETFLFEGFPYEKLQQRVLy 86

                        90       100
                ....*....|....*....|.
gi 14249340 703 --VMDYDWKSRNDFIGQYTLP 721
Cdd:cd08386  87 lqVLDYDRFSRNDPIGEVSLP 107

C2B_Munc13-like

cd04009

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

626-716

3.25e-08

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: 53.01 E-value: 3.25e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 626 AQTLLIQVISGQQLPKVDKTkeGSiVDPLVKVQIFGVRL--DTARQETNyVENNGFNPYWGQtlCFRVLVP------ELA 697
Cdd:cd04009  15 EQSLRVEILNARNLLPLDSN--GS-SDPFVKVELLPRHLfpDVPTPKTQ-VKKKTLFPLFDE--SFEFNVPpeqcsvEGA 88

                        90
                ....*....|....*....
gi 14249340 698 MLRFVVMDYDWKSRNDFIG 716
Cdd:cd04009  89 LLLFTVKDYDLLGSNDFEG 107

EFh_PI-PLCbeta3

cd16210

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

149-273

5.33e-08

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: 52.61 E-value: 5.33e-08

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 149 NQDGKMSFQEVQRLLHL--MNVEMDQEYAFSLFQAADTSQSGTLEGEEFVQFYKALTKRAEVQELFESFSADGQK-LTLL 225
Cdd:cd16210  12 NQDGRIPVKNILKMFSAdkKRVETALESCGLKFNRSESIKPDEFTLEIFERFLNKLCLRPDIDKILLEIGAKGKPyLTLE 91

                        90       100       110       120       130
                ....*....|....*....|....*....|....*....|....*....|....*...
gi 14249340 226 EFLDFLQeeQKERD----------CTSELALELIDRYEPSDSGKLRHVLSMDGFLSYL 273
Cdd:cd16210  92 QLMDFIN--QKQRDprlnevlyppLRPSQVRQLIEKYEPNQQFLERDQMSMEGFSRYL 147

C2A_Synaptotagmin-15-17

cd08390

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

627-725

1.10e-07

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: 51.10 E-value: 1.10e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 627 QTLLIQVISGQQLPKVDKTKEGSivDPLVKVQIFGvrlDTARQETNYVENNGFNPYWGQTLCFRVLVPEL--AMLRFVVM 704
Cdd:cd08390  14 EQLTVSLIKARNLPPRTKDVAHC--DPFVKVCLLP---DERRSLQSKVKRKTQNPNFDETFVFQVSFKELqrRTLRLSVY 88

                        90       100
                ....*....|....*....|.
gi 14249340 705 DYDWKSRNDFIGQYTLPWTCM 725
Cdd:cd08390  89 DVDRFSRHCIIGHVLFPLKDL 109

EFh

cd00051

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...

147-200

3.45e-07

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

Pssm-ID: 238008 [Multi-domain] Cd Length: 63 Bit Score: 47.93 E-value: 3.45e-07

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....
gi 14249340 147 DKNQDGKMSFQEVQRLLHLMNVEMDQEYAFSLFQAADTSQSGTLEGEEFVQFYK 200
Cdd:cd00051  10 DKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVDKDGDGKIDFEEFLELMA 63

PH_PLC_plant-like

cd13365

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

34-124

5.46e-07

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: 48.82 E-value: 5.46e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  34 KLRYFRLQNDGMTV-WhaRQARGSAKPSFSISDVETIRNGHDSELLRSLAEELPLEQGFTIVFHGRRSNLDLMANSVEEA 112
Cdd:cd13365  26 HFRYFWLSPDELTLyW--SSPKKGSEKRVRLSSVSRIIPGQRTVVFKRPPPPGLEEHSFSIIYADGERSLDLTCKDRQEF 103

                        90
                ....*....|..
gi 14249340 113 QIWMRGLQLLVD 124
Cdd:cd13365 104 DTWFTGLRYLLS 115

pfam00169

PH domain; PH stands for pleckstrin homology.

17-123

6.19e-07

PH domain; PH stands for pleckstrin homology.

Pssm-ID: 459697 [Multi-domain] Cd Length: 105 Bit Score: 48.33 E-value: 6.19e-07

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340    17 LMQEGMPMRKV--RSKSWKKlRYFRLQNDGMTVWHARQARGSAKPSFSIsDVETIRNGHDSELlrslaEELPLEQGFTIV 94
Cdd:pfam00169   1 VVKEGWLLKKGggKKKSWKK-RYFVLFDGSLLYYKDDKSGKSKEPKGSI-SLSGCEVVEVVAS-----DSPKRKFCFELR 73

                          90       100       110
                  ....*....|....*....|....*....|.
gi 14249340    95 FHGRRSN--LDLMANSVEEAQIWMRGLQLLV 123
Cdd:pfam00169  74 TGERTGKrtYLLQAESEEERKDWIKAIQSAI 104

PH_PLC_fungal

cd13360

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

18-129

7.05e-07

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: 48.72 E-value: 7.05e-07

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  18 MQEGMPMRKVRSKSwKKLRYFRLQND-GMTVWHarqaRGSAKPSFSISDVETIRNGHDSellRSLAEELPLEQGF----- 91
Cdd:cd13360   1 LRQGTPLLKVTKKK-KKRILFKLDPEsGKITWD----SKKPSKSLYIDDIKEIRTGEDA---RNYREEFGISEEFedrwi 72

                        90       100       110       120
                ....*....|....*....|....*....|....*....|....*.
gi 14249340  92 TIVFHGRRSN----LDLMANSVEEAQIWMRGLQLLV----DLVTSM 129
Cdd:cd13360  73 TIIYFVPKKNklktLHLIADTEEDFKLWTTTLEGLVklrrELMESL 118

EFh_PI-PLCbeta4

cd16211

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

193-277

1.46e-06

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: 48.57 E-value: 1.46e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 193 EEFVQFYKALTKRAEVQELFESFSADGQK-LTLLEFLDFLQEEQKERDCTSEL--------ALELIDRYEPSDSGKLRHV 263
Cdd:cd16211  60 EKFYELYHKICPRTDIEELFKKINGDKKDyLTVDQLISFLNEHQRDPRLNEILfpfydrkrVMQIIETYEVDEEFKKKEQ 139

                        90
                ....*....|....
gi 14249340 264 LSMDGFLSYLCSKD 277
Cdd:cd16211 140 LSSDGFCRYLMSDE 153

EFh_HEF_SCGN

cd16178

EF-hand, calcium binding motif, found in secretagogin (SCGN); SCGN is a six EF-hand ...

81-202

1.50e-06

EF-hand, calcium binding motif, found in secretagogin (SCGN); SCGN is a six EF-hand calcium-binding protein expressed in neuroendocrine, pancreatic endocrine and retinal cells. It plays a crucial role in cell apoptosis, receptor signaling and differentiation. It is also involved in vesicle secretion through binding to various proteins, including interacts with SNAP25, SNAP23, DOC2alpha, ARFGAP2, rootletin, KIF5B, beta-tubulin, DDAH-2, ATP-synthase and myeloid leukemia factor 2. SCGN functions as a calcium sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. It also serves as a calcium buffer in neurons. Thus, SCGN may be linked to the pathogenesis of neurological diseases such as Alzheimer's, and also acts as a serum marker of neuronal damage, or as a tumor biomarker. SCGN consists of the three globular domains each of which contains a pair of EF-hand motifs. All six EF hand motifs of SCGN in some eukaryotes, including D. rerio, X. laevis, M. domestica, G. gallus, O. anatinus, could potentially bind six calcium ions. In contrast, SCGNs from higher eukaryotes have at least one non-functional EF-hand motif due to the mutation(s) or deletions. For instance, the EF1 loop does not coordinate calcium ion due to the key residue asparagine replaced by lysine in SCGNs of many mammalian species. Moreover, the EF2 loop seems to be competent for calcium-binding in most mammalian SCGNs except for human and chimpanzee orthologs.

Pssm-ID: 320078 [Multi-domain] Cd Length: 257 Bit Score: 50.48 E-value: 1.50e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  81 LAEELPLEQGFTIVFHGRRSNLDlmaNSVEEAQIWMR----------GLQL---LVDLVT---SMDHQERLDQWLSDWFQ 144
Cdd:cd16178  67 LANIILPDDENFLLFFRREEPLD---SSVEFMRIWRKydadssgyisAAELknfLRDLFLqhkKVITEDKLDEYTDTMMK 143

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 145 RGDKNQDGKMSFQEVQRLLHL------------MNVEMDQEYAFSLFQAADTSQSGTLEGEEFVQFYKAL 202
Cdd:cd16178 144 IFDKNKDGRLDLNDMARILALqenfllqfkmdaMSEEERKRDFEKIFAHYDVSKTGALEGPEVDGFVKDM 213

C2B_Synaptotagmin-17

cd08410

C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking ...

626-717

2.41e-06

C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. 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 second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 176055 [Multi-domain] Cd Length: 135 Bit Score: 47.58 E-value: 2.41e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 626 AQTLLIQVISGQQLPKVDKTkEGSivDPLVKVQ-IFGVRLdTARQETNYVENNgFNPYWGQTLCFRVLVPEL--AMLRFV 702
Cdd:cd08410  13 AGRLNVDIIRAKQLLQTDMS-QGS--DPFVKIQlVHGLKL-IKTKKTSCMRGT-IDPFYNESFSFKVPQEELenVSLVFT 87

                        90
                ....*....|....*
gi 14249340 703 VMDYDWKSRNDFIGQ 717
Cdd:cd08410  88 VYGHNVKSSNDFIGR 102

EF-hand_7

pfam13499

EF-hand domain pair;

143-200

3.71e-06

EF-hand domain pair;

Pssm-ID: 463900 [Multi-domain] Cd Length: 67 Bit Score: 44.94 E-value: 3.71e-06

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340   143 FQRGDKNQDGKMSFQEVQRLLH--LMNVEMDQEYAFSLFQAADTSQSGTLEGEEFVQFYK 200
Cdd:pfam13499   8 FKLLDSDGDGYLDVEELKKLLRklEEGEPLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67

EFh_PI-PLCbeta2

cd16209

EF-hand motif found in phosphoinositide phospholipase C beta 2 (PI-PLC-beta2); PI-PLC-beta2, ...

195-274

4.19e-06

EF-hand motif found in phosphoinositide phospholipase C beta 2 (PI-PLC-beta2); PI-PLC-beta2, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2, or phospholipase C-beta-2 (PLC-beta2), is expressed at highest levels in cells of hematopoietic origin. It is activated by the heterotrimeric G protein alpha q subunits (G alpha(q)) through their C2 domain and long C-terminal extension. It is also activated by the beta-gamma subunits of heterotrimeric G proteins. PI-PLC-beta2 has two cellular binding partners, alpha- and gamma-synuclein. The binding of either alpha- and gamma-synuclein inhibits PI-PLC-beta2 activity through preventing the binding of its activator G alpha(q). However, the binding of gamma-synuclein to PI-PLC-beta2 does not affect its binding to G beta(gamma) subunits or small G proteins, but enhances these signals. Meanwhile, gamma-synuclein may protect PI-PLC-beta2 from protease degradation and contribute to its over-expression in breast cancer. In leukocytes, the G beta(gamma)-mediated activation of PI-PLC-beta2 can be promoted by a scaffolding protein WDR26, which is also required for the translocation of PI-PLC-beta2 from the cytosol to the membrane in polarized leukocytes. PI-PLC-beta2 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: 320039 Cd Length: 151 Bit Score: 47.18 E-value: 4.19e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 195 FVQFYKALTKRAEVQELFESFSADGQK-LTLLEFLDFLQEEQKERDCTSEL--------ALELIDRYEPSDSGKLRHVLS 265
Cdd:cd16209  60 FKTFLMQLCPRPEIDEIFTSYHAKAKPyMTKEHLTKFINKKQRDSRLNEELfpparpdqVQGLIEKYEPSGINAQRGQLS 139


                ....*....
gi 14249340 266 MDGFLSYLC 274
Cdd:cd16209 140 PEGMVWFLC 148

C2B_Synaptotagmin-7

cd08405

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

626-722

6.06e-06

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: 46.26 E-value: 6.06e-06

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 626 AQTLLIQVISGQQLPKVDKTkeGSiVDPLVKVQIF--GVRLDTARQETNYvenNGFNPYWGQTLCFRVLVPEL--AMLRF 701
Cdd:cd08405  14 ANRITVNIIKARNLKAMDIN--GT-SDPYVKVWLMykDKRVEKKKTVIKK---RTLNPVFNESFIFNIPLERLreTTLII 87

                        90       100
                ....*....|....*....|.
gi 14249340 702 VVMDYDWKSRNDFIGQYTLPW 722
Cdd:cd08405  88 TVMDKDRLSRNDLIGKIYLGW 108

C2B_Ferlin

cd04011

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

631-718

2.19e-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: 44.10 E-value: 2.19e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 631 IQVISGQQLPkvdktkeGSIVDPLVKVQIFGVRLDTARQE-TNyvenngfNPYWGQTLCFRVLVPELAM----LRFVVMD 705
Cdd:cd04011   8 VRVIEARQLV-------GGNIDPVVKVEVGGQKKYTSVKKgTN-------CPFYNEYFFFNFHESPDELfdkiIKISVYD 73

                        90
                ....*....|...
gi 14249340 706 YDWKSRNDFIGQY 718
Cdd:cd04011  74 SRSLRSDTLIGSF 86

C2A_RIM1alpha

cd04031

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

625-717

2.75e-05

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: 44.16 E-value: 2.75e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 625 KAQTLLIQVISGQQLPKVDktkEGSIVDPLVKVQIFGVRLDTARQETNYVENNgFNPYWGQTLCFRVLVPELAM---LRF 701
Cdd:cd04031  14 VTSQLIVTVLQARDLPPRD---DGSLRNPYVKVYLLPDRSEKSKRRTKTVKKT-LNPEWNQTFEYSNVRRETLKertLEV 89

                        90
                ....*....|....*.
gi 14249340 702 VVMDYDWKSRNDFIGQ 717
Cdd:cd04031  90 TVWDYDRDGENDFLGE 105

C2B_Synaptotagmin-4

cd08404

C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...

626-731

3.05e-05

C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. 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: 176049 [Multi-domain] Cd Length: 136 Bit Score: 44.34 E-value: 3.05e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 626 AQTLLIQVISGQQLPKVDKTkegSIVDPLVKVQIFGVRLDTARQETnYVENNGFNPYWGQTLCFRVLVPEL--AMLRFVV 703
Cdd:cd08404  14 TNRLTVVVLKARHLPKMDVS---GLADPYVKVNLYYGKKRISKKKT-HVKKCTLNPVFNESFVFDIPSEELedISVEFLV 89

                        90       100
                ....*....|....*....|....*...
gi 14249340 704 MDYDWKSRNDFIGQYTLPWTCMQQGYRH 731
Cdd:cd08404  90 LDSDRVTKNEVIGRLVLGPKASGSGGHH 117

EFh_HEF_CBN

cd16179

EF-hand, calcium binding motif, found in Drosophila melanogaster calbindin-32 (CBN) and ...

78-202

3.19e-05

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

Pssm-ID: 320079 [Multi-domain] Cd Length: 261 Bit Score: 46.25 E-value: 3.19e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  78 LRSLAEELPLEQGFTIVFHgRRSNLDlmaNSVEEAQIWMRG-----------------LQLLVDLVTSMDH-QERLDQWL 139
Cdd:cd16179  68 IRELAQLLPTEENFLLLFR-RDNPLD---SSVEFMKVWREYdkdnsgyieadelknflKHLLKEAKRDNDVsEDKLIEYT 143

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 14249340 140 SDWFQRGDKNQDGKMSFQEVQRLL---------------HLMNVEmDQEYAFSLFqaaDTSQSGTLEGEEFVQFYKAL 202
Cdd:cd16179 144 DTILQLFDRNKDGKLQLSEMARLLpvkenflcrpifkgaGKLTRE-DIDRVFALY---DRDNNGTIENEELTGFLKDL 217

PH_PLC_gamma

cd13362

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

21-124

4.80e-05

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: 43.42 E-value: 4.80e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  21 GMPMRKVRSKSWKKLRYFRLQNDGMTVWHARQARGSAKPSFSISDVETIRNGHDSELLRSLAEELP-LEQG--FTIvFHG 97
Cdd:cd13362   4 GTVMTKFYQKKRPERRTFQVKLETRQVVWSRGGGKRAEGAVDIREIKEIRPGKNSKDFERWPDEAKkLDPSccFVI-LYG 82

                        90       100       110
                ....*....|....*....|....*....|
gi 14249340  98 ---RRSNLDLMANSVEEAQIWMRGLQLLVD 124
Cdd:cd13362  83 tefRLKTLSVAATSEEECDMWIKGLRYLVE 112

C2_PKC_alpha_gamma

cd04026

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

629-716

5.70e-05

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.

Pssm-ID: 175992 [Multi-domain] Cd Length: 131 Bit Score: 43.40 E-value: 5.70e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 629 LLIQVISGQQLPKVDKTkegSIVDPLVKVQIFGVRLDTARQETNYVENNgFNPYWGQTLCFRvLVP--ELAMLRFVVMDY 706
Cdd:cd04026  15 LTVEVREAKNLIPMDPN---GLSDPYVKLKLIPDPKNETKQKTKTIKKT-LNPVWNETFTFD-LKPadKDRRLSIEVWDW 89

                        90
                ....*....|
gi 14249340 707 DWKSRNDFIG 716
Cdd:cd04026  90 DRTTRNDFMG 99

C2C_Ferlin

cd04018

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

650-718

7.66e-05

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

Pssm-ID: 175985 [Multi-domain] Cd Length: 151 Bit Score: 43.39 E-value: 7.66e-05

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 650 IVDPLVKVQIFGVRLDTARQETNYvenngfNPYWGQTLCFRVLVPELA-MLRFVVMDYDWKSRNDFIGQY 718
Cdd:cd04018  34 LVDPYVEVSFAGQKVKTSVKKNSY------NPEWNEQIVFPEMFPPLCeRIKIQIRDWDRVGNDDVIGTH 97

C2A_Synaptotagmin-1-5-6-9-10

cd08385

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

624-721

8.25e-05

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: 42.64 E-value: 8.25e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 624 FKAQTLLIQVISGQQLPKVDKtkeGSIVDPLVKVQIFGvrlDTARQETNYVENNGFNPYWGQTLCFRVLVPELA--MLRF 701
Cdd:cd08385  13 FQSNQLTVGIIQAADLPAMDM---GGTSDPYVKVYLLP---DKKKKFETKVHRKTLNPVFNETFTFKVPYSELGnkTLVF 86

                        90       100
                ....*....|....*....|
gi 14249340 702 VVMDYDWKSRNDFIGQYTLP 721
Cdd:cd08385  87 SVYDFDRFSKHDLIGEVRVP 106

C2B_Synaptotagmin-1

cd08402

C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...

626-720

9.46e-05

C2 domain second repeat present in Synaptotagmin 1; 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 the 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. It, like synaptotagmin-2, has an N-glycosylated N-terminus. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. 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: 176047 [Multi-domain] Cd Length: 136 Bit Score: 42.77 E-value: 9.46e-05

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 626 AQTLLIQVISGQQLPKVDKtkeGSIVDPLVKVQIFGVRLDTARQETNyVENNGFNPYWGQTLCFRVLVPELAMLRFV--V 703
Cdd:cd08402  14 AGKLTVVILEAKNLKKMDV---GGLSDPYVKIHLMQNGKRLKKKKTT-IKKRTLNPYYNESFSFEVPFEQIQKVHLIvtV 89

                        90
                ....*....|....*..
gi 14249340 704 MDYDWKSRNDFIGQYTL 720
Cdd:cd08402  90 LDYDRIGKNDPIGKVVL 106

C2B_RasA1_RasA4

cd04025

C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...

628-727

1.09e-04

C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase activating protein 1s ), Ras-specific GAP members, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both proteins contain two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 175991 [Multi-domain] Cd Length: 123 Bit Score: 42.47 E-value: 1.09e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 628 TLLIQVISGQQLPKVDKTKEGsivDPLVKVqifgvRLDTARQETNYVENNGFnPYWGQTLCFRVLVPELAMLRFVVMDYD 707
Cdd:cd04025   1 RLRCHVLEARDLAPKDRNGTS---DPFVRV-----FYNGQTLETSVVKKSCY-PRWNEVFEFELMEGADSPLSVEVWDWD 71

                        90       100
                ....*....|....*....|
gi 14249340 708 WKSRNDFIGQYTLPWTCMQQ 727
Cdd:cd04025  72 LVSKNDFLGKVVFSIQTLQQ 91

PI-PLCc_bacteria_like

cd08557

Catalytic domain of bacterial phosphatidylinositol-specific phospholipase C and similar ...

295-432

1.29e-04

Catalytic domain of bacterial phosphatidylinositol-specific phospholipase C and similar proteins; This subfamily corresponds to the catalytic domain present in bacterial phosphatidylinositol-specific phospholipase C (PI-PLC, EC 4.6.1.13) and their sequence homologs found in eukaryota. Bacterial PI-PLCs participate in Ca2+-independent PI metabolism, hydrolyzing the membrane lipid phosphatidylinositol (PI) to produce phosphorylated myo-inositol and diacylglycerol (DAG). Although their precise physiological function remains unclear, bacterial PI-PLCs may function as virulence factors in some pathogenic bacteria. Bacterial PI-PLCs contain a single TIM-barrel type catalytic domain. Its catalytic mechanism is based on general base and acid catalysis utilizing two well conserved histidines, and consists of two steps, a phosphotransfer and a phosphodiesterase reaction. Eukaryotic homologs in this family are named as phosphatidylinositol-specific phospholipase C X domain containing proteins (PI-PLCXD). They are distinct from the typical eukaryotic phosphoinositide-specific phospholipases C (PI-PLC, EC 3.1.4.11), which have a multidomain organization that consists of a PLC catalytic core domain, and various regulatory domains. The catalytic core domain is assembled from two highly conserved X- and Y-regions split by a divergent linker sequence. In contrast, eukaryotic PI-PLCXDs contain a single TIM-barrel type catalytic domain, X domain, which is closely related to that of bacterial PI-PLCs. Although the biological function of eukaryotic PI-PLCXDs still remains unclear, it may be distinct from that of typical eukaryotic PI-PLCs. This family also includes a distinctly different type of eukaryotic PLC, glycosylphosphatidylinositol-specific phospholipase C (GPI-PLC), an integral membrane protein characterized in the protozoan parasite Trypanosoma brucei. T. brucei GPI-PLC hydrolyzes the GPI-anchor on the variant specific glycoprotein (VSG), releasing dimyristyl glycerol (DMG), which may facilitate the evasion of the protozoan to the host's immune system. It does not require Ca2+ for its activity and is more closely related to bacterial PI-PLCs, but not mammalian PI-PLCs.

Pssm-ID: 176500 [Multi-domain] Cd Length: 271 Bit Score: 44.39 E-value: 1.29e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 295 PLNHYFICSSHN--TYLVGDQLCGQSSV----EGYIR-ALKRGCRCVEVDVW-DGPSGEPVVYHGHTLTSRILFKDVVAT 366
Cdd:cd08557   8 PLSQLSIPGTHNsyAYTIDGNSPIVSKWsktqDLSITdQLDAGVRYLDLRVAyDPDDGDLYVCHGLFLLNGQTLEDVLNE 87

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 14249340 367 VAQYAFQTSDYPVILSLETHCSWEQQQTMA---RHLTEILGEQLLST-TLDGVLPTqLpspEELRR-KILV 432
Cdd:cd08557  88 VKDFLDAHPSEVVILDLEHEYGGDNGEDHDeldALLRDVLGDPLYRPpVRAGGWPT-L---GELRAgKRVL 154

EFh_CREC_cab45

cd16225

EF-hand, calcium binding motif, found in 45 kDa calcium-binding protein (Cab45); Cab45, also ...

130-260

1.70e-04

EF-hand, calcium binding motif, found in 45 kDa calcium-binding protein (Cab45); Cab45, also termed stromal cell-derived factor 4 (SDF-4), is a soluble, lumenal Golgi resident low-affinity Ca2+-binding protein that contains six copies of the EF-hand Ca2+-binding motif. It is required for secretory pathway calcium ATPase1 (SPCA1)-dependent Ca2+ import into the trans-Golgi network (TGN) and plays an essential role in Ca2+-dependent secretory cargo sorting at the TGN.

Pssm-ID: 320023 [Multi-domain] Cd Length: 278 Bit Score: 44.21 E-value: 1.70e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 130 DHQERLDQWLSDWFQRGDKNQDGKMSFQEVQR-LLHLMNVEMDQ--EYAFSLFQAADTSQSGTLEGEEF-VQFYKA---- 201
Cdd:cd16225  27 DSEPKKRKKLKEIFKKVDVNTDGFLSAEELEDwIMEKTQEHFQEavEENEQIFKAVDTDKDGNVSWEEYrVHFLLSkgys 106

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 202 LTKRAEVQELFES------------------FSAD---GQKLTLLEFLDFLQEEQkERDCTSELALELIDRYEPSDSGKL 260
Cdd:cd16225 107 EEEAEEKIKNNEElkldeddkevldrykdrwSQADepeDGLLDVEEFLSFRHPEH-SRGMLKNMVKEILHDLDQDGDEKL 185

EFh_PEF_ALG-2_like

cd16185

EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...

139-219

2.06e-04

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

Pssm-ID: 320060 [Multi-domain] Cd Length: 163 Bit Score: 42.59 E-value: 2.06e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 139 LSDWFQRGDKNQDGKMSFQEVQRLLHLMNVEMDQEYAFSLFQAADTSQSGTLEGEEFVQFYKALTKraeVQELFESFSAD 218
Cdd:cd16185   2 LRQWFRAVDRDRSGSIDVNELQKALAGGGLLFSLATAEKLIRMFDRDGNGTIDFEEFAALHQFLSN---MQNGFEQRDTS 78


                .
gi 14249340 219 G 219
Cdd:cd16185  79 R 79

C2E_Ferlin

cd04037

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

633-717

2.15e-04

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: 41.77 E-value: 2.15e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 633 VISGQQLPKVDktkEGSIVDPLVKVQIFGVRLDTarqETNYVENnGFNPYWGQTLCFRVLVPELAMLRFVVMDYDWKSRN 712
Cdd:cd04037   6 VVRARNLQPKD---PNGKSDPYLKIKLGKKKIND---RDNYIPN-TLNPVFGKMFELEATLPGNSILKISVMDYDLLGSD 78


                ....*
gi 14249340 713 DFIGQ 717
Cdd:cd04037  79 DLIGE 83

EFh_PI-PLCepsilon

cd16203

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

222-277

2.50e-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: 2.50e-04

                        10        20        30        40        50
                ....*....|....*....|....*....|....*....|....*....|....*.
gi 14249340 222 LTLLEFLDFLQEEQKErDCTSELALELIDRYEPSDSGKLRHVLSMDGFLSYLCSKD 277
Cdd:cd16203 120 LTISQLKDFLENHQME-HITEEEAIKIIQRHEPDPILRSKNCLSFEGFARYLMDKD 174

EFh

cd00051

EF-hand, calcium binding motif; A diverse superfamily of calcium sensors and calcium signal ...

173-232

2.87e-04

Pssm-ID: 238008 [Multi-domain] Cd Length: 63 Bit Score: 39.45 E-value: 2.87e-04

                        10        20        30        40        50        60
                ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 14249340 173 EYAFSLFqaaDTSQSGTLEGEEFVQFYKAL---TKRAEVQELFESFSADGQ-KLTLLEFLDFLQ 232
Cdd:cd00051   3 REAFRLF---DKDGDGTISADELKAALKSLgegLSEEEIDEMIREVDKDGDgKIDFEEFLELMA 63

EFh_PEF_ALG-2_like

cd16185

EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...

133-232

4.65e-04

Pssm-ID: 320060 [Multi-domain] Cd Length: 163 Bit Score: 41.43 E-value: 4.65e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 133 ERLDQWLSDW---FQRGDKNQDGKMSFQEVQRLLHLMNVEMDQEYAFSLFQAADTSQSGTLEGEEFVQF--YKALTKRae 207
Cdd:cd16185  59 AALHQFLSNMqngFEQRDTSRSGRLDANEVHEALAASGFQLDPPAFQALFRKFDPDRGGSLGFDDYIELciFLASARN-- 136

                        90       100
                ....*....|....*....|....*
gi 14249340 208 vqeLFESFSADGQKLTLLEFLDFLQ 232
Cdd:cd16185 137 ---LFQAFDRQRTGRVTLDFNQFVY 158

EFh_PI-PLCgamma1_like

cd16216

EF-hand motif found in 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like ...

138-277

6.75e-04

EF-hand motif found in 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like proteins; This family corresponds to a small group of uncharacterized 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1-like (PI-PLC-gamma1-like) proteins. Although their biological function remains unclear, they shows high sequence similarity with other phosphoinositide phospholipase C gamma proteins. They contain a core set of domains, including an N-terminal pleckstrin homology (PH) domain, four atypical EF-hand motifs, a PLC catalytic core, and a single C2 domain. The PLC catalytic core domain is a TIM barrel with two highly conserved regions (X and Y) split by a highly degenerate linker sequence. A second PH domain, which is split by two SH2 (Src homology 2) domains, and one SH3 (Src homology 3) domain, are present within this linker.

Pssm-ID: 320046 Cd Length: 150 Bit Score: 40.69 E-value: 6.75e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 138 WLSDWFQRGDKNQDGKMSFQEVQRLLHLMNVEMDQeYAFSLFQAADTSQSGTLEGEEFVQFYKAL---TKRAEVQELFES 214
Cdd:cd16216   1 WLRKQFDGMDRSREGSITVKDLKALLPQVNYRVPN-MRFLRDKLVEVEARSELTFPHFIQFYKNLmfdAQKSIIEQLELS 79

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 14249340 215 F---SADGQKL---TLLEFLDFLQEEQKErDCTSELAL---ELIDRYEPSDSGKLRHVLSMDGFLSYLCSKD 277
Cdd:cd16216  80 FplrNVDRPELcqiSLYDFQKFLQHDQKE-SWASDVGRvrdYLCGYLKESSNEAPEPSLQLDEFLTYLFSKE 150

C2_PSD

cd04039

C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the ...

631-732

7.91e-04

C2 domain present in Phosphatidylserine decarboxylase (PSD); PSD is involved in the biosynthesis of aminophospholipid by converting phosphatidylserine (PtdSer) to phosphatidylethanolamine (PtdEtn). There is a single C2 domain present and it is thought to confer PtdSer binding motif that is common to PKC and synaptotagmin. 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: 176004 [Multi-domain] Cd Length: 108 Bit Score: 39.54 E-value: 7.91e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 631 IQVISGQQLPKV-DKTKEGSIVDPLVkVQIFGVRldTARqeTNYVENNgFNPYWGQTLCFRVLVPELAM-LRFVVMDYDW 708
Cdd:cd04039   5 MEIKSITDLPPLkNMTRTGFDMDPFV-IISFGRR--VFR--TSWRRHT-LNPVFNERLAFEVYPHEKNFdIQFKVLDKDK 78

                        90       100
                ....*....|....*....|....
gi 14249340 709 KSRNDFIGQYTLPWTCMQQGYRHI 732
Cdd:cd04039  79 FSFNDYVATGSLSVQELLNAAPQP 102

cd00821

Pleckstrin homology (PH) domain; PH domains have diverse functions, but in general are ...

20-119

8.82e-04

Pleckstrin homology (PH) 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: 275388 [Multi-domain] Cd Length: 92 Bit Score: 39.06 E-value: 8.82e-04

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340  20 EGMPMRK--VRSKSWKKlRYFRLQNDGMTVWHARQARGS-AKPSFSISDVETIRNGHDSELlrslaeelplEQGFTIVFH 96
Cdd:cd00821   2 EGYLLKRggGGLKSWKK-RWFVLFEGVLLYYKSKKDSSYkPKGSIPLSGILEVEEVSPKER----------PHCFELVTP 70

                        90       100
                ....*....|....*....|...
gi 14249340  97 GRRSnLDLMANSVEEAQIWMRGL 119
Cdd:cd00821  71 DGRT-YYLQADSEEERQEWLKAL 92

EFh_PEF_ALG-2_like

cd16185

EF-hand, calcium binding motif, found in homologs of mammalian apoptosis-linked gene 2 protein ...

147-231

1.03e-03

Pssm-ID: 320060 [Multi-domain] Cd Length: 163 Bit Score: 40.66 E-value: 1.03e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 147 DKNQDGKMSFQEVQRLlH--LMNVemdqeyaFSLFQAADTSQSGTLEGEEfvqFYKALTKRA------EVQELFESFsaD 218
Cdd:cd16185  46 DRDGNGTIDFEEFAAL-HqfLSNM-------QNGFEQRDTSRSGRLDANE---VHEALAASGfqldppAFQALFRKF--D 112

                        90
                ....*....|...
gi 14249340 219 GQKLTLLEFLDFL 231
Cdd:cd16185 113 PDRGGSLGFDDYI 125

C2_KIAA0528-like

cd08688

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the ...

631-717

1.30e-03

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the Human KIAA0528 cDNA clone. All members here contain a single C2 repeat. 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: 176070 [Multi-domain] Cd Length: 110 Bit Score: 39.21 E-value: 1.30e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 631 IQVISGQQLPKVDKTKEgsIVDPLVKVqifgvRLDTARQETNyVENNGFNPYWgQTLCFRVLVPELAM----LRFVVMDY 706
Cdd:cd08688   3 VRVVAARDLPVMDRSSD--LTDAFVEV-----KFGSTTYKTD-VVKKSLNPVW-NSEWFRFEVDDEELqdepLQIRVMDH 73

                        90
                ....*....|.
gi 14249340 707 DWKSRNDFIGQ 717
Cdd:cd08688  74 DTYSANDAIGK 84

C2A_Rasal1_RasA4

cd04054

C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 ...

628-720

2.84e-03

C2 domain first repeat present in RasA1 and RasA4; Rasal1 and RasA4 are both members of GAP1 (GTPase activating protein 1). Rasal1 responds to repetitive Ca2+ signals by associating with the plasma membrane and deactivating Ras. RasA4 suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. Both of these proteins contains two C2 domains, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.

Pssm-ID: 176018 [Multi-domain] Cd Length: 121 Bit Score: 38.27 E-value: 2.84e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 628 TLLIQVISGQQLPKVDKTkeGSiVDP--LVKVQIFGVrldtARQETNYvenNGFNPYWGQTLCFRvLVPELAMLRFVVMD 705
Cdd:cd04054   1 SLYIRIVEGKNLPAKDIT--GS-SDPycIVKVDNEVI----IRTATVW---KTLNPFWGEEYTVH-LPPGFHTVSFYVLD 69

                        90
                ....*....|....*
gi 14249340 706 YDWKSRNDFIGQYTL 720
Cdd:cd04054  70 EDTLSRDDVIGKVSL 84

C2B_Rabphilin_Doc2

cd08384

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

652-731

3.69e-03

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

Pssm-ID: 176030 [Multi-domain] Cd Length: 133 Bit Score: 38.10 E-value: 3.69e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 652 DPLVKVQIFGVRLDTARQETNyVENNGFNPYWGQTLCFRVLVPELA--MLRFVVMDYDWKSRNDFIGQYTLPWTCMQQGY 729
Cdd:cd08384  35 DPFVKLYLKPDAGKKSKHKTQ-VKKKTLNPEFNEEFFYDIKHSDLAkkTLEITVWDKDIGKSNDYIGGLQLGINAKGERL 113


                ..
gi 14249340 730 RH 731
Cdd:cd08384 114 RH 115

C2A_Rabphilin_Doc2

cd04035

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

651-721

4.99e-03

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

Pssm-ID: 176000 [Multi-domain] Cd Length: 123 Bit Score: 37.65 E-value: 4.99e-03

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 14249340 651 VDPLVKVQIFGVRLDTARQETNYVENNgFNPYWGQTLCFRVLVPE---LAMLRFVVMDYDwKSRNDFIGQYTLP 721
Cdd:cd04035  36 SDPYVKLNLLPGASKATKLRTKTVHKT-RNPEFNETLTYYGITEEdiqRKTLRLLVLDED-RFGNDFLGETRIP 107

EFh_HEF

cd15902

EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand ...

144-276

5.46e-03

EF-hand, calcium binding motif, found in the hexa-EF hand proteins family; The hexa-EF hand proteins family, also named the calbindin sub-family, contains a group of six EF-hand Ca2+-binding proteins, including calretinin (CR, also termed 29 kDa calbindin), calbindin D28K (CB, also termed vitamin D-dependent calcium-binding protein, avian-type), and secretagogin (SCGN). CR is a cytosolic hexa-EF-hand calcium-binding protein predominantly expressed in a variety of normal and tumorigenic t-specific neurons of the central and peripheral nervous system. It is a multifunctional protein implicated in many biological processes, including cell proliferation, differentiation, and cell death. CB is highly expressed in brain tissue. It is a strong calcium-binding and buffering protein responsible for preventing a neuronal death as well as maintaining and controlling calcium homeostasis. SCGN is a six EF-hand calcium-binding protein expressed in neuroendocrine, pancreatic endocrine and retinal cells. It plays a crucial role in cell apoptosis, receptor signaling and differentiation. It is also involved in vesicle secretion through binding to various proteins, including interacts with SNAP25, SNAP23, DOC2alpha, ARFGAP2, rootletin, KIF5B, beta-tubulin, DDAH-2, ATP-synthase and myeloid leukemia factor 2. SCGN functions as a Ca2+ sensor/coincidence detector modulating vesicular exocytosis of neurotransmitters, neuropeptides or hormones. Although the family members share a significant amount of secondary sequence homology, they display altered structural and biochemical characteristics, and operate in distinct fashions. CB contains six EF-hand motifs in a single globular domain, where EF-hands 1, 3, 4, 5 bind four calcium ions. CR contains six EF-hand motifs within two independent domains, CR I-II and CR III-VI. They harbor two and four EF-hand motifs, respectively. The first 5 EF-hand motifs are capable of binding calcium ions, while the EF-hand 6 is inactive. SCGN consists of the three globular domains each of which contains a pair of EF-hand motifs. Human SCGN simultaneously binds four calcium ions through its EF-hands 3, 4, 5 and 6 in one high affinity and three low affinity calcium-binding sites. In contrast, SCGNs in other lower eukaryotes, such as D. rerio, X. laevis, M. domestica, G. gallus, O. anatinus, are fully competent in terms of six calcium-binding.

Pssm-ID: 320075 [Multi-domain] Cd Length: 254 Bit Score: 39.26 E-value: 5.46e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 144 QRGDKNQDGKMSFQEVQ----------RLLHLMNVEMDQEYAFSLFQAADTSQSGTLEGEEFVQFYKALTK--------- 204
Cdd:cd15902  51 EKYDENEDGKIEIRELAnilpteenflLLFRREQPLISSVEFMKIWRKYDTDGSGFIEAKELKGFLKDLLLknkkhvspp 130

                        90       100       110       120       130       140       150       160
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 205 --RAEVQELFESFSADGQ-KLTLLEF--LDFLQEEQKERD--------CTSELAlELIDRYEPSDSGKLrHVLSMDGFLS 271
Cdd:cd15902 131 klDEYTKLILKEFDANKDgKLELDEMakLLPVQENFLLKFqilgamdlTKEDFE-KVFEHYDKDNNGVI-EGNELDALLK 208


                ....*
gi 14249340 272 YLCSK 276
Cdd:cd15902 209 DLLEK 213

EFh_PI-PLCgamma1

cd16214

EF-hand motif found in phosphoinositide phospholipase C gamma 1 (PI-PLC-gamma1); PI-PLC-gamma1, ...

138-277

6.30e-03

EF-hand motif found in phosphoinositide phospholipase C gamma 1 (PI-PLC-gamma1); PI-PLC-gamma1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase gamma-1, or PLC-148, or phospholipase C-II (PLC-II), or phospholipase C-gamma-1 (PLC-gamma-1), is abundantly expressed in embryonal cortical structures, neurons, oligodendrocytes and astrocytes, and is involved in various cellular events, including proliferation, differentiation, migration, survival, and cell death. It also associates with many diseases, including epilepsy, Huntington's disease (HD), depression, Alzheimer's disease (AD) and bipolar disorder. PI-PLC-gamma1 plays a critical role in cell migration and tumor cell invasiveness and metastasis. It can mediate the cell motility effects of growth factors, including platelet-derived growth factor (PDGF), epidermal growth factor (EGF), insulin-like growth factor (IGF) and hepatocyte growth factor (HGF), as well as adhesion receptors. Moreover, PI-PLC-gamma1 can modulate neurite outgrowth, neuronal cell migration and synaptic plasticity through the Trk receptor. PI-PLC-gamma1 contains 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. Besides, PI-PLC-gamma1 has a second PH domain, two SH2 (Src homology 2) regions, and one SH3 (Src homology 3) region, which are present within this linker. PI-PLC-gamma1 is activated by receptor and non-receptor tyrosine kinases via its two SH2 and a single SH3 domain.

Pssm-ID: 320044 Cd Length: 146 Bit Score: 37.88 E-value: 6.30e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 138 WLSDWFQRGDKNQDGKMSFQEVQRLLHLMNVEMDQeYAFSLFQAADTSQ-SGTLEGEEFVQFYKAL----TKRAEVQELF 212
Cdd:cd16214   1 WLRKQFYSVDRNREDRISVKDLKNMLSQVNYRVPN-MKFLREKLTDLELrSGDITYGQFAQLYRSLmfdaQKTMEVPFLE 79

                        90       100       110       120       130       140       150
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 14249340 213 ESFSADGQKLTLLEFLDFLQEEQKERDCTSELAL-ELIDRY--EPsdsgkLRHV----LSMDGFLSYLCSKD 277
Cdd:cd16214  80 RFEEREECKISLEDFQKFLLDYQKELWATDTNQVqEFMFNFlrDP-----LREIeepyFSLDEFLTFLFSKE 146

C2_putative_Elicitor-responsive_gene

cd04049

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

652-721

6.87e-03

C2 domain present in the putative elicitor-responsive gene; In plants elicitor-responsive proteins are triggered in response to specific elicitor molecules such as glycolproteins, peptides, carbohydrates and lipids. A host of defensive responses are also triggered resulting in localized cell death. Antimicrobial secondary metabolites, such as phytoalexins, or defense-related proteins, including pathogenesis-related (PR) proteins are also produced. There is a single C2 domain present here. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-II topology.

Pssm-ID: 176014 [Multi-domain] Cd Length: 124 Bit Score: 37.31 E-value: 6.87e-03

                        10        20        30        40        50        60        70
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 14249340 652 DPLVKVQiFGvrldTARQETNYVENNGFNPYWGQTLCFRVLVPE---LAMLRFVVMDYDWKSRNDFIGQYTLP 721
Cdd:cd04049  23 DPYVIIQ-CR----TQERKSKVAKGDGRNPEWNEKFKFTVEYPGwggDTKLILRIMDKDNFSDDDFIGEATIH 90

UgpQ

COG0584

Glycerophosphoryl diester phosphodiesterase [Lipid transport and metabolism];

319-354

9.21e-03

Glycerophosphoryl diester phosphodiesterase [Lipid transport and metabolism];

Pssm-ID: 440349 [Multi-domain] Cd Length: 238 Bit Score: 38.70 E-value: 9.21e-03

                        10        20        30
                ....*....|....*....|....*....|....*....
gi 14249340 319 SVEGYIRALKRGCRCVEVDVW---DgpsGEPVVYHGHTL 354
Cdd:COG0584  19 TLAAFRAALELGADGIELDVQltkD---GVLVVFHDPTL 54

EFh_PEF_Group_I

cd16180

Penta-EF hand, calcium binding motifs, found in Group I PEF proteins; The family corresponds ...

139-220

9.58e-03

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

Pssm-ID: 320055 [Multi-domain] Cd Length: 164 Bit Score: 37.51 E-value: 9.58e-03

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 14249340 139 LSDWFQRGDKNQDGKMSFQEVQRLL--------HLMNVEMdqeyAFSLFqaaDTSQSGTLEGEEFVQFYKALtkrAEVQE 210
Cdd:cd16180   2 LRRIFQAVDRDRSGRISAKELQRALsngdwtpfSIETVRL----MINMF---DRDRSGTINFDEFVGLWKYI---QDWRR 71

                        90
                ....*....|
gi 14249340 211 LFESFSADGQ 220
Cdd:cd16180  72 LFRRFDRDRS 81

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