NCBI Conserved Domain Search

Conserved domains on [gi|160331885|sp|P10895|]

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RecName: Full=1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase delta-1; AltName: Full=Phosphoinositide phospholipase C-delta-1; AltName: Full=Phospholipase C-III; Short=PLC-III; AltName: Full=Phospholipase C-delta-1; Short=PLC-delta-1

Protein Classification

PLC family C2 domain-containing protein; PLC-delta family PH domain-containing protein( domain architecture ID 11598547)

PLC (phosphoinositide-specific phospholipase C) family C2 domain-containing protein similar to C2 domain region of PLCs that are involved in the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PIP2) to d-myo-inositol-1,4,5-trisphosphate (1,4,5-IP3) and sn-1,2-diacylglycerol (DAG)| PLC-delta family PH (pleckstrin homology) domain-containing protein similar to PH region of phospholipase C-delta (PLC-delta) that functions as a calcium amplifier within the cell

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List of domain hits

Name

Accession

Description

Interval

E-value

PI-PLCc_delta

cd08593

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

295-596

8.64e-176

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: 503.79 E-value: 8.64e-176

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 295 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVVRAIR 374
Cdd:cd08593    1 YQDMTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDGPDGEPIIYHGHTLTSKILFKDVIQAIR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 375 DYAFKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLDRPLDGVVTSLPSPEQLrgkillkgkklgglfppggeggp 454
Cdd:cd08593   81 EYAFKVSPYPVILSLENHCSVEQQKVMAQHLKSILGDKLLTQPLDGVLTALPSPEEL----------------------- 137

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 455 eatvvsdedeaaemedeavRSQVQHKSKedKLRLAKELSDMVIYCKSVHFRGFPSSGTsGQAFYEMSSFSENRALRLLQE 534
Cdd:cd08593  138 -------------------KGKILVKGK--KLKLAKELSDLVIYCKSVHFKSFEHSKE-NYHFYEMSSFSESKALKLAQE 195

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 160331885 535 SGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRFLDN 596
Cdd:cd08593  196 SGNEFVRHNKRQLSRIYPAGLRTDSSNYDPQEMWNVGCQIVALNFQTPGEEMDLNDGLFRQN 257

EFh_PI-PLCdelta1

cd16217

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

144-283

2.54e-83

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: 260.83 E-value: 2.54e-83

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 144 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFKECDHSQTDSLEDEEIETFYKILTQRKEIDRTFEEATG 223
Cdd:cd16217    1 WIHSCLRKADKNKDNKMSFKELKDFLKEINIEVDDDYAEKLFKECDKSKSGFLEGEEIEEFYKLLTKREEIDVIFGEYAK 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 224 SKETLSVDQLVTFLQHQQREEEaGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 283
Cdd:cd16217   81 SDGTMSRNNLLNFLQEEQREEV-APAYALSLIEKYEPDETAKAQRQMTKDGFLMYLLSPE 139

PH_PLC_delta

cd13363

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

22-139

5.08e-67

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: 216.80 E-value: 5.08e-67

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885  22 LLKGGQLLKVKSNSWRRERFYKLQEDCKTIWQESRKvMRTPESQLFSIEDIQEVRMGHRTEGLEKFARDVPENRCFSIVF 101
Cdd:cd13363    1 LLQGSPLLKVRSRSWKKERFYKLQEDCKTVWHESKK-TRSNSKQTFSIEDIESVREGHQSEGLRKYAEAFPEDRCFSIVF 79

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 160331885 102 KDQRNTLDLIAPSPADAQHWVQGLGKIIHHSGSMDQQQ 139
Cdd:cd13363   80 KGRRKNLDLIAPSEEEAQRWVRGLEKLIARLTNMSQRE 117

C2_PLC_like

cd00275

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

628-755

3.09e-56

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: 188.13 E-value: 3.09e-56

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 628 PKRLNVRVISGQQLPKVNKNKNSIVDPKVTVEIHGVSRDV-ASRQTAVVTNNGFNPWWDTELEFEVAVPELALVRFVVED 706
Cdd:cd00275    1 PLTLTIKIISGQQLPKPKGDKGSIVDPYVEVEIHGLPADDsAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVYD 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 160331885 707 YDaSSKNDFIGQSTIPLKSLKQGYRHIHLLSKNGDQHPSATLFVKVALQ 755
Cdd:cd00275   81 ED-SGDDDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDIT 128

Name

Accession

Description

Interval

E-value

PI-PLCc_delta

cd08593

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

295-596

8.64e-176

Pssm-ID: 176535 [Multi-domain] Cd Length: 257 Bit Score: 503.79 E-value: 8.64e-176

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 295 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVVRAIR 374
Cdd:cd08593    1 YQDMTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDGPDGEPIIYHGHTLTSKILFKDVIQAIR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 375 DYAFKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLDRPLDGVVTSLPSPEQLrgkillkgkklgglfppggeggp 454
Cdd:cd08593   81 EYAFKVSPYPVILSLENHCSVEQQKVMAQHLKSILGDKLLTQPLDGVLTALPSPEEL----------------------- 137

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 455 eatvvsdedeaaemedeavRSQVQHKSKedKLRLAKELSDMVIYCKSVHFRGFPSSGTsGQAFYEMSSFSENRALRLLQE 534
Cdd:cd08593  138 -------------------KGKILVKGK--KLKLAKELSDLVIYCKSVHFKSFEHSKE-NYHFYEMSSFSESKALKLAQE 195

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 160331885 535 SGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRFLDN 596
Cdd:cd08593  196 SGNEFVRHNKRQLSRIYPAGLRTDSSNYDPQEMWNVGCQIVALNFQTPGEEMDLNDGLFRQN 257

EFh_PI-PLCdelta1

cd16217

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

144-283

2.54e-83

Pssm-ID: 320047 [Multi-domain] Cd Length: 139 Bit Score: 260.83 E-value: 2.54e-83

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 144 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFKECDHSQTDSLEDEEIETFYKILTQRKEIDRTFEEATG 223
Cdd:cd16217    1 WIHSCLRKADKNKDNKMSFKELKDFLKEINIEVDDDYAEKLFKECDKSKSGFLEGEEIEEFYKLLTKREEIDVIFGEYAK 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 224 SKETLSVDQLVTFLQHQQREEEaGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 283
Cdd:cd16217   81 SDGTMSRNNLLNFLQEEQREEV-APAYALSLIEKYEPDETAKAQRQMTKDGFLMYLLSPE 139

PI-PLC-X

pfam00388

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

298-432

6.77e-82

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: 257.05 E-value: 6.77e-82

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885  298 MDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVVRAIRDYA 377
Cdd:pfam00388   1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 160331885  378 FKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLDRPLDGVVTSLPSPEQLR 432
Cdd:pfam00388  81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLDDDLTELPSPEDLK 135

PLN02228

Phosphoinositide phospholipase C

213-755

2.76e-79

Phosphoinositide phospholipase C

Pssm-ID: 177873 [Multi-domain] Cd Length: 567 Bit Score: 264.98 E-value: 2.76e-79

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 213 EIDRTFEeATGSKETLSVDQLVTFLQHQQREEEAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSADGSAFDLAhR 292
Cdd:PLN02228  25 SIKRLFE-AYSRNGKMSFDELLRFVSEVQGERHAGLDYVQDIFHSVKHHNVFHHHGLVHLNAFYRYLFSDTNSPLPMS-G 102

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 293 RVYQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPN-QEPIIYHGYTFTSKILFCDVVR 371
Cdd:PLN02228 103 QVHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSgNAAEVRHGRTLTSHEDLQKCLN 182

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 372 AIRDYAFKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLdRPLDGVVTSLPSPEQLRGKILLKGKklgglfpPGGE 451
Cdd:PLN02228 183 AIKDNAFQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGMLF-RCTSESTKHFPSPEELKNKILISTK-------PPKE 254

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 452 GGPEATVVSDEDEAAEMEDEAVRSQVQHKSKEDKLRL---AKELSDMViyckSVHfrgfpsSGTSGQAFYEMSSFSENRA 528
Cdd:PLN02228 255 YLESKTVQTTRTPTVKETSWKRVADAENKILEEYKDEeseAVGYRDLI----AIH------AANCKDPLKDCLSDDPEKP 324

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 529 LR----------LLQESGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRFLDNGA 598
Cdd:PLN02228 325 IRvsmdeqwletMVRTRGTDLVRFTQRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFNMQGHGKQLWIMQGMFRANGG 404

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 599 CGYVLKPAFLRDPNSTFNSraLAHGPWWTPkrLNVRVISGQ----QLPKVNKNKNSIVDPKVTVEIHGVSRDVASRQTAV 674
Cdd:PLN02228 405 CGYVKKPRILLDEHTLFDP--CKRLPIKTT--LKVKIYTGEgwdlDFHLTHFDQYSPPDFFVKIGIAGVPRDTVSYRTET 480

                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 675 VTNNGFNPWWDTELEFEVAVPELALVRFVVEDYDASSKNDFIGQSTIPLKSLKQGYRHIHLLSKNGDQHPSATLFVKVAL 754
Cdd:PLN02228 481 AVDQWFPIWGNDEFLFQLRVPELALLWFKVQDYDNDTQNDFAGQTCLPLPELKSGVRAVRLHDRAGKAYKNTRLLVSFAL 560


                 .
gi 160331885 755 Q 755
Cdd:PLN02228 561 D 561

PLCXc

smart00148

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

298-432

4.98e-72

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: 231.02 E-value: 4.98e-72

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885   298 MDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVVRAIRDYA 377
Cdd:smart00148   1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 160331885   378 FKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLDRPLDGVVTSLPSPEQLR 432
Cdd:smart00148  81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSLEVLPSPEQLR 135

PH_PLC_delta

cd13363

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

22-139

5.08e-67

Pssm-ID: 270169 Cd Length: 117 Bit Score: 216.80 E-value: 5.08e-67

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885  22 LLKGGQLLKVKSNSWRRERFYKLQEDCKTIWQESRKvMRTPESQLFSIEDIQEVRMGHRTEGLEKFARDVPENRCFSIVF 101
Cdd:cd13363    1 LLQGSPLLKVRSRSWKKERFYKLQEDCKTVWHESKK-TRSNSKQTFSIEDIESVREGHQSEGLRKYAEAFPEDRCFSIVF 79

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 160331885 102 KDQRNTLDLIAPSPADAQHWVQGLGKIIHHSGSMDQQQ 139
Cdd:cd13363   80 KGRRKNLDLIAPSEEEAQRWVRGLEKLIARLTNMSQRE 117

C2_PLC_like

cd00275

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

628-755

3.09e-56

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 188.13 E-value: 3.09e-56

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 628 PKRLNVRVISGQQLPKVNKNKNSIVDPKVTVEIHGVSRDV-ASRQTAVVTNNGFNPWWDTELEFEVAVPELALVRFVVED 706
Cdd:cd00275    1 PLTLTIKIISGQQLPKPKGDKGSIVDPYVEVEIHGLPADDsAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVYD 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 160331885 707 YDaSSKNDFIGQSTIPLKSLKQGYRHIHLLSKNGDQHPSATLFVKVALQ 755
Cdd:cd00275   81 ED-SGDDDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDIT 128

EF-hand_like

pfam09279

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

204-288

7.04e-48

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: 163.57 E-value: 7.04e-48

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885  204 FYKILTQRKEIDRTFEEATGSKETLSVDQLVTFLQHQQREEEAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 283
Cdd:pfam09279   1 FYKMLTQREEIDEIFQEYSGDGQKLSLDELVDFLREEQREEDASPALALSLIERYEPSETAKKQHAMTKDGFLMYLCSPD 80


                  ....*
gi 160331885  284 GSAFD 288
Cdd:pfam09279  81 GSIFN 85

smart00239

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

630-735

1.01e-23

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: 96.02 E-value: 1.01e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885   630 RLNVRVISGQQLPKvnKNKNSIVDPKVTVEIHGVsrDVASRQTAVVTNNGfNPWWDTELEFEVAVPELALVRFVVEDYDA 709
Cdd:smart00239   1 TLTVKIISARNLPP--KDKGGKSDPYVKVSLDGD--PKEKKKTKVVKNTL-NPVWNETFEFEVPPPELAELEIEVYDKDR 75

                           90       100
                   ....*....|....*....|....*.
gi 160331885   710 SSKNDFIGQSTIPLKSLKQGYRHIHL 735
Cdd:smart00239  76 FGRDDFIGQVTIPLSDLLLGGRHEKL 101

pfam00168

C2 domain;

630-734

7.45e-21

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 88.14 E-value: 7.45e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885  630 RLNVRVISGQQLPkvNKNKNSIVDPKVTVEIHgvsRDVASRQTAVVtNNGFNPWWDTELEFEVAVPELALVRFVVEDYDA 709
Cdd:pfam00168   2 RLTVTVIEAKNLP--PKDGNGTSDPYVKVYLL---DGKQKKKTKVV-KNTLNPVWNETFTFSVPDPENAVLEIEVYDYDR 75

                          90       100
                  ....*....|....*....|....*
gi 160331885  710 SSKNDFIGQSTIPLKSLKQGYRHIH 734
Cdd:pfam00168  76 FGRDDFIGEVRIPLSELDSGEGLDG 100

COG5038

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

631-729

3.20e-09

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 60.54 E-value: 3.20e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885  631 LNVRVISGQQLPKVNKNKNSivDPKVTVEIHGVSrdvaSRQTAVVTNNgFNPWWDTELEFEVAVPELALVRFVVEDYDAS 710
Cdd:COG5038  1042 LTIMLRSGENLPSSDENGYS--DPFVKLFLNEKS----VYKTKVVKKT-LNPVWNEEFTIEVLNRVKDVLTINVNDWDSG 1114

                          90
                  ....*....|....*....
gi 160331885  711 SKNDFIGQSTIPLKSLKQG 729
Cdd:COG5038  1115 EKNDLLGTAEIDLSKLEPG 1133

smart00233

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

22-130

4.68e-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: 51.40 E-value: 4.68e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885    22 LLKGGQLLKVKS--NSWRRERFYKLQEDCKTIWQESRKVMRTPESQLFSIEDIQeVRMGHRTEglekfarDVPENRCFSI 99
Cdd:smart00233   1 VIKEGWLYKKSGggKKSWKKRYFVLFNSTLLYYKSKKDKKSYKPKGSIDLSGCT-VREAPDPD-------SSKKPHCFEI 72

                           90       100       110
                   ....*....|....*....|....*....|.
gi 160331885   100 VFKDqRNTLDLIAPSPADAQHWVQGLGKIIH 130
Cdd:smart00233  73 KTSD-RKTLLLQAESEEEREKWVEALRKAIA 102

PH_12

pfam16457

Pleckstrin homology domain;

19-125

7.33e-05

Pleckstrin homology domain;

Pssm-ID: 465123 [Multi-domain] Cd Length: 128 Bit Score: 43.02 E-value: 7.33e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885   19 LQALLKGGQLLKVKSNS-WRRERFYKLQEDCKTIW----QESRKVMRTPESQLFSIE--DIQEVRMGHRTE---GLEKFA 88
Cdd:pfam16457   6 LNCLLEGAWFPKVRGRRrKKKYRFCRLSPNRKVLHygdfEEKPTVDPSLESLPEKIDlsDIKEVVTGKECPhvrESGKKS 85

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 160331885   89 RDVPENRCFSIVF-KDQRNTLDLIAPSPADAQHWVQGL 125
Cdd:pfam16457  86 KKTSSTLAFSLIYgADEYELLDFVAPSESVAAIWLDGL 123

Name

Accession

Description

Interval

E-value

PI-PLCc_delta

cd08593

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

295-596

8.64e-176

Pssm-ID: 176535 [Multi-domain] Cd Length: 257 Bit Score: 503.79 E-value: 8.64e-176

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 295 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVVRAIR 374
Cdd:cd08593    1 YQDMTQPLSHYFIASSHNTYLLEDQLKGPSSTEAYIRALKKGCRCVELDCWDGPDGEPIIYHGHTLTSKILFKDVIQAIR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 375 DYAFKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLDRPLDGVVTSLPSPEQLrgkillkgkklgglfppggeggp 454
Cdd:cd08593   81 EYAFKVSPYPVILSLENHCSVEQQKVMAQHLKSILGDKLLTQPLDGVLTALPSPEEL----------------------- 137

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 455 eatvvsdedeaaemedeavRSQVQHKSKedKLRLAKELSDMVIYCKSVHFRGFPSSGTsGQAFYEMSSFSENRALRLLQE 534
Cdd:cd08593  138 -------------------KGKILVKGK--KLKLAKELSDLVIYCKSVHFKSFEHSKE-NYHFYEMSSFSESKALKLAQE 195

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 160331885 535 SGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRFLDN 596
Cdd:cd08593  196 SGNEFVRHNKRQLSRIYPAGLRTDSSNYDPQEMWNVGCQIVALNFQTPGEEMDLNDGLFRQN 257

PI-PLCc_delta1

cd08629

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

295-596

4.57e-156

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: 453.34 E-value: 4.57e-156

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 295 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVVRAIR 374
Cdd:cd08629    1 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVLRAIR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 375 DYAFKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLDRPLDGVVTSLPSPEQLRGkillkgkklgglfppggeggp 454
Cdd:cd08629   81 DYAFKASPYPVILSLENHCSLEQQRVMARHLRAILGPILLDQPLDGVTTSLPSPEQLKG--------------------- 139

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 455 eatvvsdedeaaemedeavRSQVQHKskedKLRLAKELSDMVIYCKSVHFRGFPSSGTSGQAFYEMSSFSENRALRLLQE 534
Cdd:cd08629  140 -------------------KILLKGK----KLKLVPELSDMIIYCKSVHFGGFSSPGTSGQAFYEMASFSESRALRLLQE 196

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 160331885 535 SGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRFLDN 596
Cdd:cd08629  197 SGNGFVRHNVSCLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGPEMDVYLGCFQDN 258

PI-PLCc_eukaryota

cd08558

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

295-596

3.96e-137

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: 403.37 E-value: 3.96e-137

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 295 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVVRAIR 374
Cdd:cd08558    1 YQDMTQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGHTLTSKILFKDVIEAIK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 375 DYAFKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLDRPLDGVVTSLPSPEQLRgkillkgkklgglfppggeggp 454
Cdd:cd08558   81 EYAFVTSPYPVILSLENHCSLEQQKKMAQILKEIFGDKLLTPPLDENPVQLPSPEQLK---------------------- 138

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 455 eatvvsdedeaaemedeavrsqvqHKSkedklrlakelsdmVIYCKSvhfrgfpssgtsgqafYEMSSFSENRALRLLQE 534
Cdd:cd08558  139 ------------------------GKI--------------LIKGKK----------------YHMSSFSETKALKLLKE 164

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 160331885 535 SGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRFLDN 596
Cdd:cd08558  165 SPEEFVKYNKRQLSRVYPKGTRVDSSNYNPQPFWNAGCQMVALNYQTPDLPMQLNQGKFEQN 226

PI-PLCc_delta3

cd08630

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

295-596

1.59e-130

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: 387.84 E-value: 1.59e-130

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 295 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVVRAIR 374
Cdd:cd08630    1 FQDMSQPLAHYFISSSHNTYLTDSQIGGPSSTEAYVRAFAQGCRCVELDCWEGPGGEPVIYHGHTLTSKILFRDVIQAVR 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 375 DYAFKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLDRPLDGV-VTSLPSPEQLrgkillkgkklgglfppggegg 453
Cdd:cd08630   81 QHAFTASPYPVILSLENHCGLEQQAAMARHLQTILGDMLVTQPLDSLnPEELPSPEEL---------------------- 138

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 454 peatvvsdedeaaemedeavRSQVQHKSKedKLRLAKELSDMVIYCKSVHFRGFPSSGTSGQAfYEMSSFSENRALRLLQ 533
Cdd:cd08630  139 --------------------KGRVLVKGK--KLQISPELSALAVYCQATRLRTLEPAPVQPQP-CQVSSLSERKAKKLIR 195

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 160331885 534 ESGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRFLDN 596
Cdd:cd08630  196 EAGNSFVRHNARQLTRVYPLGLRMNSANYSPQEMWNSGCQLVALNFQTPGYEMDLNAGRFLVN 258

PI-PLCc_delta4

cd08631

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

295-596

6.08e-128

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: 381.22 E-value: 6.08e-128

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 295 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVVRAIR 374
Cdd:cd08631    1 YQDMTQPLCHYFICSSHNTYLMEDQLRGQSSVEGYIRALKRGCRCVEVDVWDGPNGEPIVYHGHTFTSKILFKDVVAAVA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 375 DYAFKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLDRPLDGVV-TSLPSPEQLrgkillkgkklgglfppggegg 453
Cdd:cd08631   81 QYAFQVSDYPVILSLENHCGVEQQQTMAQHLTEILGEKLLSTTLDGVLpTQLPSPEEL---------------------- 138

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 454 peatvvsdedeaaemedeavRSQVQHKSKedKLRLAKELSDMVIYCKSVHFRGFPSSGTSGQaFYEMSSFSENRALRLLQ 533
Cdd:cd08631  139 --------------------RGKILLKGK--KIRLSPELSDCVIYCKSVSFRSFTHSREHYH-FYEISSFTETKARKLIR 195

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 160331885 534 ESGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRFLDN 596
Cdd:cd08631  196 EAGNEFVQHNTWQLSRVYPSGLRTDSSNYNPQEMWNAGCQMVALNFQTAGLEMDLNDGLFRQN 258

PI-PLCc_PRIP_metazoa

cd08597

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

296-596

5.69e-120

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: 360.58 E-value: 5.69e-120

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 296 QDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVVRAIRD 375
Cdd:cd08597    2 QDMTQPLSHYFIASSHNTYLIEDQLRGPSSVEGYVRALQRGCRCVELDCWDGPNGEPVIYHGHTLTSKISFRSVIEAINE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 376 YAFKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLDRPLDGVVTSLPSPEQLRGkillkgkklgglfppggeggpe 455
Cdd:cd08597   82 YAFVASEYPLILCIENHCSEKQQLVMAQYLKEIFGDKLYTEPPNEGESYLPSPHDLKG---------------------- 139

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 456 atvvsdedeaaemedeavrsQVQHKSKEDKLR-LAKELSDMVIYCKSVHFRGFPSSgTSGQAFYEMSSFSENRALRLLQE 534
Cdd:cd08597  140 --------------------KIIIKGKKLKRRkLCKELSDLVSLCKSVRFQDFPTS-AQNQKYWEVCSFSENLARRLANE 198

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 160331885 535 SGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRFLDN 596
Cdd:cd08597  199 FPEDFVNYNKKFLSRVYPSPMRVDSSNYNPQDFWNCGCQIVAMNYQTPGLMMDLNTGKFLEN 260

PI-PLCc_zeta

cd08595

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

295-596

1.31e-109

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: 333.83 E-value: 1.31e-109

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 295 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVVRAIR 374
Cdd:cd08595    1 YQDMDHPLSDYFISSSHNTYLVSDQLVGPSDLDGYVSALRKGCRCLEIDCWDGADNEPVVYHGYTLTSKILFKEVITTVE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 375 DYAFKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLDRPLDGV-VTSLPSPEQLRGkillkgkklgglfppggegg 453
Cdd:cd08595   81 KYAFEKSDYPVVLSLENHCSTEQQEIMAHYLVSILGEKLLRAPIDDPaTGELPSPEALKF-------------------- 140

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 454 peatvvsdedeaaemedeavRSQVQHKSKedklrLAKELSDMVIYCKSVHFRGFPSSgTSGQAFYEMSSFSENRALRLLQ 533
Cdd:cd08595  141 --------------------KILVKNKKK-----IAKALSDLVIYTKSEKFCSFTHS-RDNQHSYENNSIGENKARKLLK 194

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 160331885 534 ESGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRFLDN 596
Cdd:cd08595  195 SSGADFVGHTQRFITRIYPKGTRASSSNYNPQEFWNVGCQMVALNFQTLGAPMDLQNGKFLDN 257

PI-PLCc_beta

cd08591

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

295-593

1.38e-105

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: 323.52 E-value: 1.38e-105

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 295 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDG--PNQEPIIYHGYTFTSKILFCDVVRA 372
Cdd:cd08591    1 YQDMDQPLSHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLSGCRCIELDCWDGkgEDEEPIITHGKTMCTEILFKDVIEA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 373 IRDYAFKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLDRPLDGVV----TSLPSPEQLRGKIllkgkklgglfpp 448
Cdd:cd08591   81 IAETAFKTSEYPVILSFENHCSSKQQAKMAEYCREIFGDLLLTEPLEKYPlepgVPLPSPNDLKRKI------------- 147

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 449 ggeggpeatvvsdedeaaemedeavrsqvqhkskedkLRLAKELSDMVIYCKSVHFRGFPSSgTSGQAFYEMSSFSENRA 528
Cdd:cd08591  148 -------------------------------------LIKNKKLSSLVNYIQPVKFQGFEVA-EKRNKHYEMSSFNESKG 189

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 160331885 529 LRLLQESGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRF 593
Cdd:cd08591  190 LGYLKKSPIEFVNYNKRQLSRIYPKGTRVDSSNYMPQIFWNAGCQMVALNFQTPDLPMQLNQGKF 254

PI-PLCc_gamma

cd08592

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

296-596

1.75e-102

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: 314.36 E-value: 1.75e-102

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 296 QDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVVRAIRD 375
Cdd:cd08592    2 QDMNNPLSHYWIASSHNTYLTGDQLSSESSLEAYARCLRMGCRCIELDCWDGPDGMPIIYHGHTLTSKIKFMDVLKTIKE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 376 YAFKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLDRPLDGVVTSLPSPEQLRGkillkgkklgglfppggeggpe 455
Cdd:cd08592   82 HAFVTSEYPVILSIENHCSLPQQRNMAQAFKEVFGDMLLTQPVDRNADQLPSPNQLKR---------------------- 139

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 456 atvvsdedeaaemedeavRSQVQHKskedKLrlakelsdmviycksvhfrgfpssgtsgqaFYEMSSFSENRALRLL-QE 534
Cdd:cd08592  140 ------------------KIIIKHK----KL------------------------------FYEMSSFPETKAEKYLnRQ 167

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 160331885 535 SGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRFLDN 596
Cdd:cd08592  168 KGKIFLKYNRRQLSRVYPKGQRVDSSNYDPVPMWNCGSQMVALNFQTPDKPMQLNQALFMLN 229

PI-PLCc

cd00137

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

295-596

9.40e-98

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: 303.80 E-value: 9.40e-98

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 295 YQDMDQPLSHYLVSSSHNTYLLEDQLT-----GPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTsKILFCDV 369
Cdd:cd00137    1 HHPDTQPLAHYSIPGTHDTYLTAGQFTikqvwGLTQTEMYRQQLLSGCRCVDIRCWDGKPEEPIIYHGPTFL-DIFLKEV 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 370 VRAIRDYAFKASPYPVILSLENHCSL--EQQRVMARHLRTLLGPMLLDrPLDGVVTSLPSPEQLRGKILLKGKKLGGLFP 447
Cdd:cd00137   80 IEAIAQFLKKNPPETIIMSLKNEVDSmdSFQAKMAEYCRTIFGDMLLT-PPLKPTVPLPSLEDLRGKILLLNKKNGFSGP 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 448 PGGEGGPEAtvvsdedeaaemedeavrsqvqhkskedklrlakelsdmviycksvhfrGFPSSGTSGQAFYEMSSFSENR 527
Cdd:cd00137  159 TGSSNDTGF-------------------------------------------------VSFEFSTQKNRSYNISSQDEYK 189

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 528 ALR----LLQESGNSFVRHNVNHLSRIYPAGWR---------TDSSNYSPVEMWNG---GCQIVALNFQTPGSEMDVYQG 591
Cdd:cd00137  190 AYDdekvKLIKATVQFVDYNKNQLSRNYPSGTSggtawyyyaMDSNNYMPQMFWNAnpaGCGIVILDFQTMDLPMQQYMA 269


                 ....*
gi 160331885 592 RFLDN 596
Cdd:cd00137  270 VIEFN 274

PI-PLC1c_yeast

cd08598

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

295-593

4.99e-93

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: 289.53 E-value: 4.99e-93

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 295 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVVRAIR 374
Cdd:cd08598    1 EEDLSRPLNEYFISSSHNTYLLGRQLAGDSSVEGYIRALQRGCRCVEIDVWDGDDGEPVVTHGYTLTSSVPFRDVCRAIK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 375 DYAFKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLDRPLDGVVTSLPSPEQLRgkillkgkklgglfppggeggp 454
Cdd:cd08598   81 KYAFVTSPYPLILSLEVHCDAEQQERMVEIMKETFGDLLVTEPLDGLEDELPSPEELR---------------------- 138

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 455 eatvvsdedeaaemedeavrsqvqHKskedklrlakelsdMVIYCKsvhfrgfPSSGTsgqaFYEMSSFSENRALRLLQE 534
Cdd:cd08598  139 ------------------------GK--------------ILIKVK-------KESKT----PNHIFSLSERSLLKLLKD 169

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 160331885 535 SGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRF 593
Cdd:cd08598  170 KRAALDKHNRRHLMRVYPSGTRISSSNFNPLPFWRAGVQMVALNWQTYDLGMQLNEAMF 228

PI-PLCc_beta4

cd08626

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

295-593

8.48e-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: 277.03 E-value: 8.48e-88

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 295 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGP--NQEPIIYHGYTFTSKILFCDVVRA 372
Cdd:cd08626    1 YQDMDQPLAHYFINSSHNTYLTGRQFGGKSSVEMYRQVLLAGCRCIELDCWDGKgeDQEPIITHGKAMCTDILFKDVIQA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 373 IRDYAFKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLDRPLDGVVT----SLPSPEQLRGKIllkgkklgglfpp 448
Cdd:cd08626   81 IKDTAFVTSDYPVILSFENHCSKPQQYKLAKYCEEIFGDLLLTKPLESHPLepgvPLPSPNKLKRKI------------- 147

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 449 ggeggpeatvvsdedeaaemedeavrsqvqhkskedkLRLAKELSDMVIYCKSVHFRGFPSSGTSGQAFYeMSSFSENRA 528
Cdd:cd08626  148 -------------------------------------LIKNKRLSSLVNYAQPVKFQGFDVAEERNIHFN-MSSFNESVG 189

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 160331885 529 LRLLQESGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRF 593
Cdd:cd08626  190 LGYLKTSAIEFVNYNKRQMSRIYPKGTRVDSSNYMPQIFWNAGCQMVSLNFQTPDLGMQLNQGKF 254

PI-PLCc_gamma2

cd08628

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

296-593

1.11e-87

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: 276.55 E-value: 1.11e-87

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 296 QDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVVRAIRD 375
Cdd:cd08628    2 QDMNNPLSHYWISSSHNTYLTGDQLRSESSTEAYIRCLRMGCRCIELDCWDGPDGKPIIYHGWTRTTKIKFDDVVQAIKD 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 376 YAFKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLDRPLDGVVTSLPSPEQLRGkillkgkklgglfppggeggpe 455
Cdd:cd08628   82 HAFVTSEYPVILSIEEHCSVEQQRHMAKVFKEVFGDKLLMKPLEASADQLPSPTQLKE---------------------- 139

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 456 atvvsdedeaaemedeavRSQVQHKskedKLrLAKELSDMVIYCKSvhfRGFPSSGTSGQAFYEMSSFSENRALRLLQES 535
Cdd:cd08628  140 ------------------KIIIKHK----KL-IAIELSDLVVYCKP---TSKTKDNLENPDFKEIRSFVETKAPSIIRQK 193

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....*...
gi 160331885 536 GNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRF 593
Cdd:cd08628  194 PVQLLKYNRKGLTRVYPKGQRVDSSNYDPFRLWLCGSQMVALNFQTADKYMQLNHALF 251

EFh_PI-PLCdelta1

cd16217

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

144-283

2.54e-83

Pssm-ID: 320047 [Multi-domain] Cd Length: 139 Bit Score: 260.83 E-value: 2.54e-83

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 144 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFKECDHSQTDSLEDEEIETFYKILTQRKEIDRTFEEATG 223
Cdd:cd16217    1 WIHSCLRKADKNKDNKMSFKELKDFLKEINIEVDDDYAEKLFKECDKSKSGFLEGEEIEEFYKLLTKREEIDVIFGEYAK 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 224 SKETLSVDQLVTFLQHQQREEEaGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 283
Cdd:cd16217   81 SDGTMSRNNLLNFLQEEQREEV-APAYALSLIEKYEPDETAKAQRQMTKDGFLMYLLSPE 139

PI-PLCc_eta1

cd08632

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

295-596

4.59e-83

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: 264.58 E-value: 4.59e-83

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 295 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVVRAIR 374
Cdd:cd08632    1 NQDMDQPLCNYFIASSHNTYLTGDQLLSQSKVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKITFRDVIETIN 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 375 DYAFKASPYPVILSLENHCSLEQQRVMARHLRTLLGPML-LDRPLDGVVTSLPSPEQLrgkillkgkklgglfppggegg 453
Cdd:cd08632   81 KYAFVKNEFPVILSIENHCSIQQQKKIAQYLKEIFGDKLdLSSVLTGDPKQLPSPQLL---------------------- 138

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 454 peatvvsdedeaaemedeavRSQVQHKSKedklRLAKELSDMVIYCKSVHFRGFPSSGTSGQAFyemsSFSENRALRLLQ 533
Cdd:cd08632  139 --------------------KGKILVKGK----KLCRDLSDLVVYTNSVAAQDIVDDGSTGNVL----SFSETRAHQLVQ 190

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 160331885 534 ESGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRFLDN 596
Cdd:cd08632  191 QKAEQFMTYNQKQLTRIYPSAYRIDSSNFNPLPYWNVGCQLVALNYQSEGRMMQLNRAKFMVN 253

PI-PLCc_eta

cd08594

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

295-596

6.04e-83

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: 263.20 E-value: 6.04e-83

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 295 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVVRAIR 374
Cdd:cd08594    1 NQDMTQPLSHYFIASSHNTYLTGDQLLSQSRVDMYARVLQAGCRCVEVDCWDGPDGEPVVHHGYTLTSKILFRDVIETIN 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 375 DYAFKASPYPVILSLENHCSLEQQRVMARHLRTLLGPML-LDRPLDGVVTSLPSPEQLrgkillkgkklgglfppggegg 453
Cdd:cd08594   81 KYAFIKNEYPVILSIENHCSVQQQKKMAQYLKEILGDKLdLSSVISGDSKQLPSPQSL---------------------- 138

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 454 peatvvsdedeaaemedeavRSQVQHKSKEdklrlakelsdmviycksvhfrgfpssgtsgqafYEMSSFSENRALRLLQ 533
Cdd:cd08594  139 --------------------KGKILIKGKK----------------------------------WQVSSFSETRAHQIVQ 164

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 160331885 534 ESGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRFLDN 596
Cdd:cd08594  165 QKAAQFLRFNQRQLSRIYPSAYRIDSSNFNPQPYWNAGCQLVALNYQTEGRMLQLNRAKFRAN 227

PI-PLCc_eta2

cd08633

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

296-596

1.24e-82

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: 263.44 E-value: 1.24e-82

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 296 QDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVVRAIRD 375
Cdd:cd08633    2 QDMTQPLSHYFITSSHNTYLSGDQLMSQSRVDMYAWVLQAGCRCVEVDCWDGPDGEPIVHHGYTLTSKILFKDVIETINK 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 376 YAFKASPYPVILSLENHCSLEQQRVMARHLRTLLGPML-LDRPLDGVVTSLPSPEQLrgkillkgkklgglfppggeggp 454
Cdd:cd08633   82 YAFIKNEYPVILSIENHCSVPQQKKMAQYLTEILGDKLdLSSVISNDCTRLPSPEIL----------------------- 138

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 455 eatvvsdedeaaemedeavRSQVQHKSKedklRLAKELSDMVIYCKSVHFRGFPSSGTSGqafYEMSSFSENRALRLLQE 534
Cdd:cd08633  139 -------------------KGKILVKGK----KLSRALSDLVKYTKSVRVHDIETEATSS---WQVSSFSETKAHQILQQ 192

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 160331885 535 SGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRFLDN 596
Cdd:cd08633  193 KPAQYLRFNQRQLSRIYPSSYRVDSSNYNPQPFWNAGCQMVALNYQSEGRMLQLNRAKFSAN 254

PI-PLC-X

pfam00388

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

298-432

6.77e-82

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: 257.05 E-value: 6.77e-82

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885  298 MDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVVRAIRDYA 377
Cdd:pfam00388   1 MSQPLSHYFISSSHNTYLTGDQLTGESSVEAYIRALLRGCRCVELDCWDGPDGEPVVYHGYTLTSKIPFRDVLEAIKDYA 80

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 160331885  378 FKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLDRPLDGVVTSLPSPEQLR 432
Cdd:pfam00388  81 FVTSPYPVILSLENHCSPEQQKKMAEILKEIFGDMLYTPPLDDDLTELPSPEDLK 135

PI-PLCc_epsilon

cd08596

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

296-596

1.70e-81

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: 260.55 E-value: 1.70e-81

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 296 QDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVVRAIRD 375
Cdd:cd08596    2 EDLQYPLSYYYIESSHNTYLTGHQLKGESSVELYSQVLLTGCRCVELDCWDGDDGMPIIYHGHTLTTKIPFKDVVEAINR 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 376 YAFKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLDRPL---DGVVT-SLPSPEQLrgkillkgkklgglfppgge 451
Cdd:cd08596   82 SAFITSDYPVILSIENHCSLQQQRKMAEIFKTVFGEKLVTKFLfesDFSDDpSLPSPLQL-------------------- 141

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 452 ggpeatvvsdedeaaemedeavRSQVQHKSKEdklrlAKELSDMVIYCKSVHFRGFPSSGTsgqafYEMSSFSENRALRL 531
Cdd:cd08596  142 ----------------------KNKILLKNKK-----APELSDLVIYCQAVKFPGLSTPKC-----YHISSLNENAAKRL 189

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 160331885 532 LQESGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRFLDN 596
Cdd:cd08596  190 CRRYPQKLVQHTRCQLLRTYPAATRIDSSNPNPLIFWLHGLQLVALNYQTDDLPMHLNAAMFEAN 254

PLN02228

Phosphoinositide phospholipase C

213-755

2.76e-79

Phosphoinositide phospholipase C

Pssm-ID: 177873 [Multi-domain] Cd Length: 567 Bit Score: 264.98 E-value: 2.76e-79

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 213 EIDRTFEeATGSKETLSVDQLVTFLQHQQREEEAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSADGSAFDLAhR 292
Cdd:PLN02228  25 SIKRLFE-AYSRNGKMSFDELLRFVSEVQGERHAGLDYVQDIFHSVKHHNVFHHHGLVHLNAFYRYLFSDTNSPLPMS-G 102

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 293 RVYQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPN-QEPIIYHGYTFTSKILFCDVVR 371
Cdd:PLN02228 103 QVHHDMKAPLSHYFVYTGHNSYLTGNQVNSRSSVEPIVQALRKGVKVIELDLWPNPSgNAAEVRHGRTLTSHEDLQKCLN 182

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 372 AIRDYAFKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLdRPLDGVVTSLPSPEQLRGKILLKGKklgglfpPGGE 451
Cdd:PLN02228 183 AIKDNAFQVSDYPVVITLEDHLPPNLQAQVAKMLTKTFRGMLF-RCTSESTKHFPSPEELKNKILISTK-------PPKE 254

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 452 GGPEATVVSDEDEAAEMEDEAVRSQVQHKSKEDKLRL---AKELSDMViyckSVHfrgfpsSGTSGQAFYEMSSFSENRA 528
Cdd:PLN02228 255 YLESKTVQTTRTPTVKETSWKRVADAENKILEEYKDEeseAVGYRDLI----AIH------AANCKDPLKDCLSDDPEKP 324

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 529 LR----------LLQESGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRFLDNGA 598
Cdd:PLN02228 325 IRvsmdeqwletMVRTRGTDLVRFTQRNLVRIYPKGTRVDSSNYDPHVGWTHGAQMVAFNMQGHGKQLWIMQGMFRANGG 404

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 599 CGYVLKPAFLRDPNSTFNSraLAHGPWWTPkrLNVRVISGQ----QLPKVNKNKNSIVDPKVTVEIHGVSRDVASRQTAV 674
Cdd:PLN02228 405 CGYVKKPRILLDEHTLFDP--CKRLPIKTT--LKVKIYTGEgwdlDFHLTHFDQYSPPDFFVKIGIAGVPRDTVSYRTET 480

                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 675 VTNNGFNPWWDTELEFEVAVPELALVRFVVEDYDASSKNDFIGQSTIPLKSLKQGYRHIHLLSKNGDQHPSATLFVKVAL 754
Cdd:PLN02228 481 AVDQWFPIWGNDEFLFQLRVPELALLWFKVQDYDNDTQNDFAGQTCLPLPELKSGVRAVRLHDRAGKAYKNTRLLVSFAL 560


                 .
gi 160331885 755 Q 755
Cdd:PLN02228 561 D 561

PI-PLCc_gamma1

cd08627

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

296-596

3.59e-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: 3.59e-79

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 296 QDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVVRAIRD 375
Cdd:cd08627    2 EEMNNPLSHYWISSSHNTYLTGDQFSSESSLEAYARCLRMGCRCIELDCWDGPDGMPVIYHGHTLTTKIKFSDVLHTIKE 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 376 YAFKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLDRPLDGVVTSLPSPEQLRGkillkgkklgglfppggeggpe 455
Cdd:cd08627   82 HAFVTSEYPIILSIEDHCSIVQQRNMAQHFKKVFGDMLLTKPVDINADGLPSPNQLKR---------------------- 139

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 456 atvvsdedeaaemedeavRSQVQHKskedklrlakelsdmviycksvhfrgfpssgtsgQAFYEMSSFSENRALRLLQES 535
Cdd:cd08627  140 ------------------KILIKHK----------------------------------KLYRDMSSFPETKAEKYVNRS 167

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 160331885 536 -GNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRFLDN 596
Cdd:cd08627  168 kGKKFLQYNRRQLSRIYPKGQRLDSSNYDPLPMWICGSQLVALNFQTPDKPMQMNQALFMLG 229

PI-PLCc_beta2

cd08624

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

295-588

1.61e-77

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: 250.36 E-value: 1.61e-77

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 295 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDG--PNQEPIIYHGYTFTSKILFCDVVRA 372
Cdd:cd08624    1 HQDMTQPLNHYFINSSHNTYLTAGQFSGLSSPEMYRQVLLSGCRCVELDCWKGkpPDEEPIITHGFTMTTEILFKDAIEA 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 373 IRDYAFKASPYPVILSLENHC-SLEQQRVMARHLRTLLGPMLLDRPLD------GVvtSLPSPEQLRGkillkgkklggl 445
Cdd:cd08624   81 IAESAFKTSPYPVILSFENHVdSPKQQAKMAEYCRTIFGDMLLTEPLEkyplkpGV--PLPSPEDLRG------------ 146

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 446 fppggeggpeatvvsdedeaaemedeavRSQVQHKSKEdklrlakELSDMVIYCKSVHFRGFPSSGTSGQAfYEMSSFSE 525
Cdd:cd08624  147 ----------------------------KILIKNKKYE-------EMSSLVNYIQPTKFVSFEFSAQKNRS-YVISSFTE 190

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 160331885 526 NRALRLLQESGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTpgseMDV 588
Cdd:cd08624  191 LKAYDLLSKASVQFVEYNKRQMSRIYPKGTRMDSSNYMPQMFWNVGCQMVALNFQT----MDL 249

PI-PLCc_beta3

cd08625

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

297-593

3.80e-75

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: 243.81 E-value: 3.80e-75

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 297 DMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDG--PNQEPIIYHGYTFTSKILFCDVVRAIR 374
Cdd:cd08625    3 DMNQPLSHYFINSSHNTYLTAGQLTGLSSVEMYRQVLLTGCRCIELDCWKGrpPEEEPFITHGFTMTTEIPFKDVIEAIA 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 375 DYAFKASPYPVILSLENHC-SLEQQRVMARHLRTLLGPMLLDRPLD------GVvtSLPSPEQLRGKIllkgkklgglfp 447
Cdd:cd08625   83 ESAFKTSPYPVILSFENHVdSAKQQAKMAEYCRSIFGDALLIDPLDkyplvpGV--QLPSPQELMGKI------------ 148

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 448 pggeggpeatvvsdedeaaemedeavrsqvqhkskedkLRLAKELSDMVIYCKSVHFRGFPSSGTSGQaFYEMSSFSENR 527
Cdd:cd08625  149 --------------------------------------LVKNKKMSTLVNYIEPVKFKSFEAAAKRNK-FFEMSSFVETK 189

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 160331885 528 ALRLLQESGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRF 593
Cdd:cd08625  190 AMEQLTKSPMEFVEYNKKQLSRIYPKGTRVDSSNYMPQLFWNVGCQMVALNFQTLDLAMQLNMGVF 255

PLN02952

phosphoinositide phospholipase C

212-751

6.59e-74

phosphoinositide phospholipase C

Pssm-ID: 178538 [Multi-domain] Cd Length: 599 Bit Score: 251.46 E-value: 6.59e-74

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 212 KEIDRTFEEATGSKETLSVDQLVTFLQHQQREEEAGPALALSLIEryepsETAKAQRQMTK--------DGFLMYLLSAD 283
Cdd:PLN02952  38 DDVKDVFCKFSVGGGHMGADQLRRFLVLHQDELDCTLAEAQRIVE-----EVINRRHHVTRytrhglnlDDFFHFLLYDD 112

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 284 GSAFDLAHrrVYQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPI-IYHGYTFTS 362
Cdd:PLN02952 113 LNGPITPQ--VHHDMTAPLSHYFIYTGHNSYLTGNQLSSDCSEVPIVKALQRGVRVIELDLWPGSTKDEIlVLHGRTLTT 190

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 363 KILFCDVVRAIRDYAFKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLDRPLDGVVtSLPSPEQLR---------- 432
Cdd:PLN02952 191 PVPLIKCLKSIRDYAFSSSPYPVIITLEDHLTPDLQAKVAEMATQIFGQMLYYPESDSLV-QFPSPESLKhriiistkpp 269

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 433 ----GKILLKGKKLGGLFPPGGEGGP----EATVVSDEDEAAEMEDEAVRSQVQHKSKEDKLRLAKELSdmviyckSVHf 504
Cdd:PLN02952 270 keylESSGPIVIKKKNNVSPSGRNSSeeteEAQTLESMLFEQEADSRSDSDQDDNKSGELQKPAYKRLI-------TIH- 341

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 505 RGFPSsGTSGQAFYEMS------SFSENRALRLLQESGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALN 578
Cdd:PLN02952 342 AGKPK-GTLKDAMKVAVdkvrrlSLSEQELEKAATTNGQDVVRFTQRNILRIYPKGTRITSSNYKPLIGWMHGAQMIAFN 420

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 579 FQTPGSEMDVYQGRFLDNGACGYVLKPAFLRDP---NSTFNSR-ALAhgpwwTPKRLNVRVISGQ----QLPKVNKNKNS 650
Cdd:PLN02952 421 MQGYGKSLWLMHGMFRANGGCGYLKKPDFLMKKgfhDEVFDPKkKLP-----VKKTLKVKVYLGDgwrlDFSHTHFDSYS 495

                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 651 IVDPKVTVEIHGVSRDVASRQTAVVTNNgFNPWWDTELEFEVAVPELALVRFVVEDYDASSKNDFIGQSTIPLKSLKQGY 730
Cdd:PLN02952 496 PPDFYTKMYIVGVPADNAKKKTKIIEDN-WYPAWNEEFSFPLTVPELALLRIEVREYDMSEKDDFGGQTCLPVSELRPGI 574

                        570       580
                 ....*....|....*....|.
gi 160331885 731 RHIHLLSKNGDQHPSATLFVK 751
Cdd:PLN02952 575 RSVPLHDKKGEKLKNVRLLMR 595

PLCXc

smart00148

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

298-432

4.98e-72

Pssm-ID: 197543 [Multi-domain] Cd Length: 143 Bit Score: 231.02 E-value: 4.98e-72

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885   298 MDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVVRAIRDYA 377
Cdd:smart00148   1 MDKPLSHYFIPSSHNTYLTGKQLWGESSVEGYIQALDAGCRCVELDCWDGPDGEPVIYHGHTFTLPIKLSEVLEAIKDFA 80

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 160331885   378 FKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLDRPLDGVVTSLPSPEQLR 432
Cdd:smart00148  81 FVTSPYPVILSLENHCSPDQQAKMAQMFKEIFGDMLYTPPLTSSLEVLPSPEQLR 135

PLN02222

phosphoinositide phospholipase C 2

212-752

6.88e-71

phosphoinositide phospholipase C 2

Pssm-ID: 177868 [Multi-domain] Cd Length: 581 Bit Score: 242.63 E-value: 6.88e-71

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 212 KEIDRTFEEATgSKETLSVDQLVTFLQHQQREEEAGPALALSLIEryePSETAKAQRQMTKDGFLMYLLSADGSAfdLAH 291
Cdd:PLN02222  25 REIKTIFEKYS-ENGVMTVDHLHRFLIDVQKQDKATREDAQSIIN---SASSLLHRNGLHLDAFFKYLFGDNNPP--LAL 98

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 292 RRVYQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPI-IYHGYTFTSKILFCDVV 370
Cdd:PLN02222  99 HEVHHDMDAPISHYFIFTGHNSYLTGNQLSSDCSEVPIIDALKKGVRVIELDIWPNSDKDDIdVLHGMTLTTPVGLIKCL 178

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 371 RAIRDYAFKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLDRPLDGVVTSLPSPEQLRGKILLKGKKlgglfPPGG 450
Cdd:PLN02222 179 KAIRAHAFDVSDYPVVVTLEDHLTPDLQSKVAEMVTEIFGEILFTPPVGESLKEFPSPNSLKKRIIISTKP-----PKEY 253

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 451 EGGPEATVVSDEDEAAEMED--EAVRSQVQHKSKEDKL---------------RLAKELSDMVIYCKSVHfRGFPSSGTS 513
Cdd:PLN02222 254 KEGKDDEVVQKGKDLGDEEVwgREVPSFIQRNKSVDKNdsngddddddddgedKSKKNAPPQYKHLIAIH-AGKPKGGIT 332

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 514 GQAFYEMS-----SFSENRALRLLQESGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDV 588
Cdd:PLN02222 333 ECLKVDPDkvrrlSLSEEQLEKAAEKYAKQIVRFTQHNLLRIYPKGTRVTSSNYNPLVGWSHGAQMVAFNMQGYGRSLWL 412

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 589 YQGRFLDNGACGYVLKPAFLRDPNST---FNSRALAhgPWWTPKRLNVRVISGQ--QLPKVNKNKNSIVDPKVTVEIHGV 663
Cdd:PLN02222 413 MQGMFRANGGCGYIKKPDLLLKSGSDsdiFDPKATL--PVKTTLRVTIYMGEGWyfDFRHTHFDQYSPPDFYTRVGIAGV 490

                        490       500       510       520       530       540       550       560
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 664 SRDVASRQTAVVTNNgFNPWWDTELEFEVAVPELALVRFVVEDYDASSKNDFIGQSTIPLKSLKQGYRHIHLLSKNGDQH 743
Cdd:PLN02222 491 PGDTVMKKTKTLEDN-WIPAWDEVFEFPLTVPELALLRLEVHEYDMSEKDDFGGQTCLPVWELSQGIRAFPLHSRKGEKY 569


                 ....*....
gi 160331885 744 PSATLFVKV 752
Cdd:PLN02222 570 KSVKLLVKV 578

PH_PLC_delta

cd13363

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

22-139

5.08e-67

Pssm-ID: 270169 Cd Length: 117 Bit Score: 216.80 E-value: 5.08e-67

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885  22 LLKGGQLLKVKSNSWRRERFYKLQEDCKTIWQESRKvMRTPESQLFSIEDIQEVRMGHRTEGLEKFARDVPENRCFSIVF 101
Cdd:cd13363    1 LLQGSPLLKVRSRSWKKERFYKLQEDCKTVWHESKK-TRSNSKQTFSIEDIESVREGHQSEGLRKYAEAFPEDRCFSIVF 79

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 160331885 102 KDQRNTLDLIAPSPADAQHWVQGLGKIIHHSGSMDQQQ 139
Cdd:cd13363   80 KGRRKNLDLIAPSEEEAQRWVRGLEKLIARLTNMSQRE 117

PI-PLCc_beta1

cd08623

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

296-593

9.25e-66

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: 218.80 E-value: 9.25e-66

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 296 QDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDG--PNQEPIIYHGYTFTSKILFCDVVRAI 373
Cdd:cd08623    2 EDMSQPLSHYFINSSHNTYLTAGQLAGNSSVEMYRQVLLSGCRCVELDCWKGrtAEEEPVITHGFTMTTEISFKEVIEAI 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 374 RDYAFKASPYPVILSLENHC-SLEQQRVMARHLRTLLGPMLLDRPLD------GVvtSLPSPEQLRGKIllkgkklgglf 446
Cdd:cd08623   82 AECAFKTSPFPILLSFENHVdSPKQQAKMAEYCRLIFGDALLMEPLEkyplesGV--PLPSPMDLMYKI----------- 148

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 447 ppggeggpeatvvsdedeaaemedeavrsqvqhkskedkLRLAKELSDMVIYCKSVHFRGFPSSGTSGQAfYEMSSFSEN 526
Cdd:cd08623  149 ---------------------------------------LVKNKKMSNLVNYIQPVKFESFEASKKRNKS-FEMSSFVET 188

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 160331885 527 RALRLLQESGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRF 593
Cdd:cd08623  189 KGLEQLTKSPVEFVEYNKMQLSRIYPKGTRVDSSNYMPQLFWNAGCQMVALNFQTVDLSMQINMGMY 255

PI-PLC-Y

pfam00387

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

492-607

8.02e-64

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

Pssm-ID: 459794 Cd Length: 114 Bit Score: 208.08 E-value: 8.02e-64

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885  492 LSDMVIYCKSVHFRGFpsSGTSGQAFYEMSSFSENRALRLLQESGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGG 571
Cdd:pfam00387   1 LSDLVVYTQSVKFKSF--STPESKTPNHIFSFSESKALKLIKSSSAAFVKHNRRHLMRVYPKGTRVDSSNFNPQPFWNCG 78

                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 160331885  572 CQIVALNFQTPGSEMDVYQGRFLDNGACGYVLKPAF 607
Cdd:pfam00387  79 VQMVALNWQTPDEGMQLNEGMFADNGGCGYVLKPEF 114

PLCYc

smart00149

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

493-608

1.59e-63

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: 207.48 E-value: 1.59e-63

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885   493 SDMVIYCKSVHFRGFPSSgTSGQAFYEMSSFSENRALRLLQESGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGC 572
Cdd:smart00149   1 SDLVIYCAPVKFRSFESA-ESKNPFYEMSSFSETKAKKLLKKSPTDFVRYNQRQLSRVYPKGTRVDSSNYNPQVFWNHGC 79

                           90       100       110
                   ....*....|....*....|....*....|....*.
gi 160331885   573 QIVALNFQTPGSEMDVYQGRFLDNGACGYVLKPAFL 608
Cdd:smart00149  80 QMVALNFQTPDKPMQLNQGMFRANGGCGYVLKPDFL 115

PI-PLCc_plant

cd08599

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

295-596

4.32e-61

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: 205.30 E-value: 4.32e-61

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 295 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVVRAIR 374
Cdd:cd08599    1 HHDMTAPLSHYFIFSSHNSYLTGNQLSSRSSTAPIIEALLRGCRVIELDLWPGGRGDICVLHGGTLTKPVKFEDCIKAIK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 375 DYAFKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLDRPLDGVVTSLPSPEQLRgkillkgkklgglfppggeggp 454
Cdd:cd08599   81 ENAFTASEYPVIITLENHLSPELQAKAAQILRETLGDKLFYPDSEDLPEEFPSPEELK---------------------- 138

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 455 eatvvsdedeaaemedeavrsqvqHKskedklrlakelsdMVIYCKSVHFrgfpssgtsgqafyeMSSFSEnRALRLL-- 532
Cdd:cd08599  139 ------------------------GK--------------ILISDKPPVI---------------RNSLSE-TQLKKVie 164

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 160331885 533 QESGNSFVRHNVNHLSRIYPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRFLDN 596
Cdd:cd08599  165 GEHPTDLIEFTQKNLLRVYPAGLRITSSNYDPMLAWMHGAQMVALNMQGYDRPLWLNRGKFRAN 228

EFh_PI-PLCdelta

cd16202

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

144-283

1.15e-60

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: 200.53 E-value: 1.15e-60

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 144 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFKECDHSQTDSLEDEEIETFYKILTQRKEIDRTFEEATG 223
Cdd:cd16202    1 WLKDQFRKADKNGDGKLSFKECKKLLKKLNVKVDKDYAKKLFQEADTSGEDVLDEEEFVQFYNRLTKRPEIEELFKKYSG 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 224 SKETLSVDQLVTFLQHQQREEEAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 283
Cdd:cd16202   81 DDEALTVEELRRFLQEEQKVKDVTLEWAEQLIETYEPSEDLKAQGLMSLDGFTLFLLSPD 140

C2_PLC_like

cd00275

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

628-755

3.09e-56

Pssm-ID: 175974 [Multi-domain] Cd Length: 128 Bit Score: 188.13 E-value: 3.09e-56

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 628 PKRLNVRVISGQQLPKVNKNKNSIVDPKVTVEIHGVSRDV-ASRQTAVVTNNGFNPWWDTELEFEVAVPELALVRFVVED 706
Cdd:cd00275    1 PLTLTIKIISGQQLPKPKGDKGSIVDPYVEVEIHGLPADDsAKFKTKVVKNNGFNPVWNETFEFDVTVPELAFLRFVVYD 80

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|....*....
gi 160331885 707 YDaSSKNDFIGQSTIPLKSLKQGYRHIHLLSKNGDQHPSATLFVKVALQ 755
Cdd:cd00275   81 ED-SGDDDFLGQACLPLDSLRQGYRHVPLLDSKGEPLELSTLFVHIDIT 128

PLN02230

phosphoinositide phospholipase C 4

267-751

1.50e-54

phosphoinositide phospholipase C 4

Pssm-ID: 177875 [Multi-domain] Cd Length: 598 Bit Score: 198.01 E-value: 1.50e-54

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 267 QRQMTKDGFLMYLLSADGSAfdLAHRRVYQDMDQPLSHYLVSSSHNTYLLEDQLTGPSSTEAYIRALCKGCRCLELDCWD 346
Cdd:PLN02230  88 RRNLTLDDFNYYLFSTDLNP--PIADQVHQNMDAPLSHYFIFTGHNSYLTGNQLSSNCSELPIADALRRGVRVVELDLWP 165

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 347 GPNQEPIIYHGYTFTSKILFCDVVRAIRDYAFKASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLDRPLDGvVTSLP 426
Cdd:PLN02230 166 RGTDDVCVKHGRTLTKEVKLGKCLDSIKANAFAISKYPVIITLEDHLTPKLQFKVAKMITQTFGDMLYYHDSEG-CQEFP 244

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 427 SPEQLRGKILLKGKklgglfPP-------------GGEGG-----------PEATVVSdedeaaEMEDEAVRSQVQHKSK 482
Cdd:PLN02230 245 SPEELKEKILISTK------PPkeyleandakekdNGEKGkdsdedvwgkePEDLIST------QSDLDKVTSSVNDLNQ 312

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 483 EDKLRLAKElSDMVIYCKSVHFR-------GFPSSGTSGQAFYEMS-----SFSENRALRLLQESGNSFVRHNVNHLSRI 550
Cdd:PLN02230 313 DDEERGSCE-SDTSCQLQAPEYKrliaihaGKPKGGLRMALKVDPNkirrlSLSEQLLEKAVASYGADVIRFTQKNFLRI 391

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 551 YPAGWRTDSSNYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRFLDNGACGYVLKPAFLRDPNStfNSRALAHGPWWTPKR 630
Cdd:PLN02230 392 YPKGTRFNSSNYKPQIGWMSGAQMIAFNMQGYGRALWLMEGMFRANGGCGYVKKPDFLMDAGP--NGQDFYPKDNSCPKK 469

                        410       420       430       440       450       460       470       480
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 631 -LNVRVISGQ----QLPKVNKNKNSIVDPKVTVEIHGVSRDVASRQTAVVTNNgFNPWWDTELEFEVAVPELALVRFVVE 705
Cdd:PLN02230 470 tLKVKVCMGDgwllDFKKTHFDSYSPPDFFVRVGIAGAPVDEVMEKTKIEYDT-WTPIWNKEFIFPLAVPELALLRVEVH 548

                        490       500       510       520
                 ....*....|....*....|....*....|....*....|....*.
gi 160331885 706 DYDASSKNDFIGQSTIPLKSLKQGYRHIHLLSKNGDQHPSATLFVK 751
Cdd:PLN02230 549 EHDINEKDDFGGQTCLPVSEIRQGIHAVPLFNRKGVKYSSTRLLMR 594

EF-hand_like

pfam09279

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

204-288

7.04e-48

Pssm-ID: 401279 [Multi-domain] Cd Length: 85 Bit Score: 163.57 E-value: 7.04e-48

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885  204 FYKILTQRKEIDRTFEEATGSKETLSVDQLVTFLQHQQREEEAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 283
Cdd:pfam09279   1 FYKMLTQREEIDEIFQEYSGDGQKLSLDELVDFLREEQREEDASPALALSLIERYEPSETAKKQHAMTKDGFLMYLCSPD 80


                  ....*
gi 160331885  284 GSAFD 288
Cdd:pfam09279  81 GSIFN 85

EFh_PI-PLCdelta4

cd16219

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

144-283

6.68e-44

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: 154.62 E-value: 6.68e-44

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 144 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFKECDHSQTDSLEDEEIETFYKILTQRKEIDRTFEEATG 223
Cdd:cd16219    1 WIRDWFQKADKNKDGRMNFKEVRDLLKMMNVDMNEEHALRLFQMADKSESGTLEGEEFVLFYKALTQREDVLKIFQDFSA 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 224 SKETLSVDQLVTFLQHQQREEEAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 283
Cdd:cd16219   81 DGQKLTLLEFVDFLQQEQLERENTEELAMELIDRYEPSDTAKKLHALSIDGFLMYLCSPE 140

EFh_PI-PLCdelta3

cd16218

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

144-283

1.93e-43

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: 153.36 E-value: 1.93e-43

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 144 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFKECDHSQTDSLEDEEIETFYKILTQRKEIDRTFEEATG 223
Cdd:cd16218    1 WIHEYLRRADLNKDGKMSFEEIKDLLQMINIDLNEQYAYQLFKECDRSNDDRLEEHEIEEFCRRLMQRPELEEIFHQYSG 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 224 SKETLSVDQLVTFLQHQQreEEAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 283
Cdd:cd16218   81 EDCVLSAEELREFLKDQG--EDASLVHAKELIQTYELNEKAKQHQLMTLDGFTMYMLSKD 138

EFh_PI-PLC

cd15898

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

144-283

5.38e-38

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

Pssm-ID: 320029 [Multi-domain] Cd Length: 137 Bit Score: 138.18 E-value: 5.38e-38

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 144 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFKECDHSQTDSLEDEEIETFYKILTQRKEIDRTFEEATG 223
Cdd:cd15898    1 WLRRQWIKADKDGDGKLSLKEIKKLLKRLNIRVSEKELKKLFKEVDTNGDGTLTFDEFEELYKSLTERPELEPIFKKYAG 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 160331885 224 S-KETLSVDQLVTFLQHQQREEEAgPALALSLIERYEPSETakaQRQMTKDGFLMYLLSAD 283
Cdd:cd15898   81 TnRDYMTLEEFIRFLREEQGENVS-EEECEELIEKYEPERE---NRQLSFEGFTNFLLSPE 137

PLN02223

phosphoinositide phospholipase C

295-751

6.54e-35

phosphoinositide phospholipase C

Pssm-ID: 165867 [Multi-domain] Cd Length: 537 Bit Score: 140.16 E-value: 6.54e-35

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 295 YQDMDQPLSHYLVSSSHNTYLLEDQLTGPS-STEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFTSKILFCDVVRAI 373
Cdd:PLN02223 105 HHDMHAPLSHYFIHTSLKSYFTGNNVFGKLySIEPIIDALEQGVRVVELDLLPDGKDGICVRPKWNFEKPLELQECLDAI 184

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 374 RDYAF-KASPYPVILSLENHCSLEQQRVMARHLRTLLGPMLLDRPLDGVVTSLPSPEQLRGKILLKGKklgglfPPggeg 452
Cdd:PLN02223 185 KEHAFtKCRSYPLIITFKDGLKPDLQSKATQMIDQTFGDMVYHEDPQHSLEEFPSPAELQNKILISRR------PP---- 254

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 453 gpeaTVVSDEDEAAEMEDEAVRSQVQHKSKEDKLRlakelsdMVIYCKSVHFRGFPSSGTSGQA-------FYEMS--SF 523
Cdd:PLN02223 255 ----KELLYAKADDGGVGVRNELEIQEGPADKNYQ-------SLVGFHAVEPRGMLQKALTGKAddiqqpgWYERDiiSF 323

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 524 SENRALRLLQESGNSFvrhnvnhlsrIYPAgwrtdssnYSPVEMWNGGCQIVALNFQTPGSEMDVYQGRFLDNGACGYVL 603
Cdd:PLN02223 324 TQKKFLRTRPKKKNLL----------INAP--------YKPQRAWMHGAQLIALSRKDDKEKLWLMQGMFRANGGCGYVK 385

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 604 KPAFLRD--PNSTFNsralahgPWWTP---KRLNVRVISGQQ-LPKVNKNKNSIVDPK--VTVEIHGVSRDVASRQTAVv 675
Cdd:PLN02223 386 KPDFLLNagPSGVFY-------PTENPvvvKILKVKIYMGDGwIVDFKKRIGRLSKPDlyVRISIAGVPHDEKIMKTTV- 457

                        410       420       430       440       450       460       470
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 160331885 676 TNNGFNPWWDTELEFEVAVPELALVRFVVEDYDASSKNDFIGQSTIPLKSLKQGYRHIHLLSKNGDQHPSATLFVK 751
Cdd:PLN02223 458 KNNEWKPTWGEEFTFPLTYPDLALISFEVYDYEVSTADAFCGQTCLPVSELIEGIRAVPLYDERGKACSSTMLLTR 533

PH_PLC_ELMO1

cd01248

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

22-125

6.86e-35

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

Pssm-ID: 269952 Cd Length: 108 Bit Score: 128.21 E-value: 6.86e-35

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885  22 LLKGGQLLKVKSNSWRRERFYKLQEDCKTIWQESRKVMrtPESQLFSIEDIQEVRMGHRTEGLEKF--ARDVPENRCFSI 99
Cdd:cd01248    1 LQQGTLLLKYREGSKPKERTFYLDPDGTRITWESSKKK--SEKKSIDISDIKEIRPGKDTDGFKRKkkSNKPKEERCFSI 78

                         90       100
                 ....*....|....*....|....*.
gi 160331885 100 VFKDQRNTLDLIAPSPADAQHWVQGL 125
Cdd:cd01248   79 IYGSNNKTLDLVAPSEDEANLWVEGL 104

PI-PLCc_GDPD_SF

cd08555

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

309-579

5.87e-27

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

Pssm-ID: 176498 [Multi-domain] Cd Length: 179 Bit Score: 108.29 E-value: 5.87e-27

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 309 SSHNTYLLEDQltgPSSTEAYIRALCKGCRCLELDCWDGPNQEPIIYHGYTFT------SKILFCDVVRAIRDYAFkASP 382
Cdd:cd08555    2 LSHRGYSQNGQ---ENTLEAFYRALDAGARGLELDVRLTKDGELVVYHGPTLDrttagiLPPTLEEVLELIADYLK-NPD 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 383 YPVILSLENHCS----LEQQRVMARHLRTLLGPMLLDRpldgvvtslpspeqlrgkillkgkklgglfppggeggpeaTV 458
Cdd:cd08555   78 YTIILSLEIKQDspeyDEFLAKVLKELRVYFDYDLRGK----------------------------------------VV 117

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 459 VSDedeaaemedeavrsqvqhkskedklrlakelsdmviycksvhfrgfpssgtsgqafYEMSSFSENRALRLLQESGNS 538
Cdd:cd08555  118 LSS--------------------------------------------------------FNALGVDYYNFSSKLIKDTEL 141

                        250       260       270       280
                 ....*....|....*....|....*....|....*....|..
gi 160331885 539 FVRHNV-NHLSRIYPAGWrtdsSNYSPVEMWNGGCQIVALNF 579
Cdd:cd08555  142 IASANKlGLLSRIWTVND----NNEIINKFLNLGVDGLITDF 179

smart00239

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

630-735

1.01e-23

Pssm-ID: 214577 [Multi-domain] Cd Length: 101 Bit Score: 96.02 E-value: 1.01e-23

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885   630 RLNVRVISGQQLPKvnKNKNSIVDPKVTVEIHGVsrDVASRQTAVVTNNGfNPWWDTELEFEVAVPELALVRFVVEDYDA 709
Cdd:smart00239   1 TLTVKIISARNLPP--KDKGGKSDPYVKVSLDGD--PKEKKKTKVVKNTL-NPVWNETFEFEVPPPELAELEIEVYDKDR 75

                           90       100
                   ....*....|....*....|....*.
gi 160331885   710 SSKNDFIGQSTIPLKSLKQGYRHIHL 735
Cdd:smart00239  76 FGRDDFIGQVTIPLSDLLLGGRHEKL 101

EF-hand_10

pfam14788

EF hand;

159-208

1.14e-23

EF hand;

Pssm-ID: 405477 Cd Length: 50 Bit Score: 94.02 E-value: 1.14e-23

                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 160331885  159 KMSFKELQNFLKELNIQVDDSYARKIFKECDHSQTDSLEDEEIETFYKIL 208
Cdd:pfam14788   1 KMSFKELKNFLRLINIEVDDSYARKLFQKCDTSQSGRLEGEEIEEFYKLL 50

EFh_PI-PLCeta

cd16205

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

144-283

2.15e-22

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: 93.60 E-value: 2.15e-22

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 144 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFKECDHSQTD-SLEDEEIETFYKILTQRKEIDRTFEEAT 222
Cdd:cd16205    1 WLKQTFEEADKNGDGLLSIGEILQLMHKLNVNLPRRKVRQMFKEADTDDNQgTLDFEEFCAFYKMMSTRRELYLLLLSYS 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 160331885 223 GSKETLSVDQLVTFLQHQQREEEAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 283
Cdd:cd16205   81 NKKDYLTLEDLARFLEVEQKMTNVTLEYCLDIIEKFEPSEENKKNGLLGIDGFTNYMRSPA 141

PH_PLC_eta

cd13364

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

24-125

8.57e-22

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: 90.80 E-value: 8.57e-22

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885  24 KGGQLLKVKSNSWRRERFYKLQEDCKTI-WQESRKvmrTPESQLFSIEDIQEVRMGHRTEGLEK--FARDVPENRCFSIV 100
Cdd:cd13364    3 EGSELVKVRSNSRQYRRFFYLDEDKSSIrWKPSKK---KSEKAKIPISSIREVREGKTTDIFRScdISGDFPEECCFSII 79

                         90       100
                 ....*....|....*....|....*
gi 160331885 101 FKDQRNTLDLIAPSPADAQHWVQGL 125
Cdd:cd13364   80 YGEEYETLDLVASSPDEANIWITGL 104

EFh_ScPlc1p_like

cd16207

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

143-283

3.21e-21

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: 90.39 E-value: 3.21e-21

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 143 HWihsclRKADKNK---DNKMSFKELQNFLKELNIQVDDSYARKIFKECDHSQTDSLEDEEIETFYKILTQRKEIDRTFE 219
Cdd:cd16207    4 HW-----KRADSKKqdgDERLDFEDVEKLCRRLHINCSESYLRELFDKADTDKKGYLNFEEFQEFVKLLKRRKDIKAIFK 78

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 160331885 220 EATG-SKETLSVDQLVTFLQHQQREEEAgPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 283
Cdd:cd16207   79 QLTKpGSDGLTLEEFLKFLRDVQKEDVD-RETWEKIFEKFARRIDDSDSLTMTLEGFTSFLLSSY 142

pfam00168

C2 domain;

630-734

7.45e-21

C2 domain;

Pssm-ID: 425499 [Multi-domain] Cd Length: 104 Bit Score: 88.14 E-value: 7.45e-21

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885  630 RLNVRVISGQQLPkvNKNKNSIVDPKVTVEIHgvsRDVASRQTAVVtNNGFNPWWDTELEFEVAVPELALVRFVVEDYDA 709
Cdd:pfam00168   2 RLTVTVIEAKNLP--PKDGNGTSDPYVKVYLL---DGKQKKKTKVV-KNTLNPVWNETFTFSVPDPENAVLEIEVYDYDR 75

                          90       100
                  ....*....|....*....|....*
gi 160331885  710 SSKNDFIGQSTIPLKSLKQGYRHIH 734
Cdd:pfam00168  76 FGRDDFIGEVRIPLSELDSGEGLDG 100

EFh_PI-PLCzeta

cd16204

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

153-283

5.43e-19

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: 84.09 E-value: 5.43e-19

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 153 DKNKDNKMSFKELQNFLKELNIQVDDSYARKIFKECDHSQTDSLEDEEIETFYKILTQRKEIDRTFEEATGSKETLSVDQ 232
Cdd:cd16204   12 DRFRKGKINLESTLKLLEKLDIPFDYIHVKYIFKKNDSFKAGNITIEDFRAIYRAIAHRCEIHEIFNTYSENRKILSAPN 91

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 160331885 233 LVTFLQHQQREEEAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 283
Cdd:cd16204   92 LVGFLKKEQFQDEADETIASELIAKYEPIEEVRKRKQMSFEGFIRYMTSED 142

EFh_PI-PLC21

cd16213

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

154-283

2.97e-17

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: 79.27 E-value: 2.97e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 154 KNKDNKMSFKelqNFLKELNIQVDDSyaRKIFKECD-----HSQTDS--LEDEEIETFYKI---LTQRKEIDRTFEE-AT 222
Cdd:cd16213   11 TDKEGKIPVK---NIVKMFAQHKDDR--KRVEKALEaiglpSGKNDAidPKKFTFEDFFNFyrrLTGRQEVEKIFDElGA 85

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 160331885 223 GSKETLSVDQLVTFLQHQQREEE--------AGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 283
Cdd:cd16213   86 KKKPYLTTEQFVDFLNKTQRDPRlneilypyANPKRARDLINQYEPNKSFAKKGHLSVEGFLRYLMSED 154

EFh_PRIP

cd16206

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

144-283

3.82e-17

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: 78.79 E-value: 3.82e-17

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 144 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFKECDHSQTD---SLEDEEIETFYKILTQRKEIDRTFEE 220
Cdd:cd16206    1 WLESVFEEADTNKSGFLDEEEAVQLIKQLNPGLSTSRIKQKLKELQKKKDGargRVSSDEFVELFKELATRPEIYFLLVR 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 160331885 221 ATGSKETLSVDQLVTFLQHQQREEEAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 283
Cdd:cd16206   81 YASNKDYLTVDDLMLFLEAEQGMTGVTKEKCLEIINKYEPSEEGREKGQLGIDGFTRYLLSEE 143

EFh_PI-PLCeta1

cd16220

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

144-281

1.08e-15

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: 74.68 E-value: 1.08e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 144 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFKECDHSQTD-SLEDEEIETFYKILTQRKEIDRTFEEAT 222
Cdd:cd16220    1 WVKQTFEEADKNGDGLLNIEEIYQLMHKLNVNLPRRKVRQMFQEADTDENQgTLTFEEFCVFYKMMSLRRDLYLLLLSYS 80

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 160331885 223 GSKETLSVDQLVTFLQHQQREEEAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLS 281
Cdd:cd16220   81 DKKDHLTVEELAQFLKVEQKMNNVTTEYCLDIIKKFEVSEENKEQNVLGIEGFTNFMRS 139

cd00030

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

631-728

3.29e-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: 71.71 E-value: 3.29e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 631 LNVRVISGQQLPKVNKNKNSivDPKVTVEIHGVSRdvasRQTAVVTNNgFNPWWDTELEFEVAVPELALVRFVVEDYDAS 710
Cdd:cd00030    1 LRVTVIEARNLPAKDLNGKS--DPYVKVSLGGKQK----FKTKVVKNT-LNPVWNETFEFPVLDPESDTLTVEVWDKDRF 73

                         90
                 ....*....|....*...
gi 160331885 711 SKNDFIGQSTIPLKSLKQ 728
Cdd:cd00030   74 SKDDFLGEVEIPLSELLD 91

EFh_PI-PLCeta2

cd16221

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

144-281

8.78e-15

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: 71.89 E-value: 8.78e-15

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 144 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFKECDhsqTD----SLEDEEIETFYKILTQRKEIDRTFE 219
Cdd:cd16221    1 WLKQTFDEADKNGDGSLSIGEVLQLLHKLNVNLPRQKVKQMFKEAD---TDdnqgTLGFEEFCAFYKMMSTRRDLYLLML 77

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 160331885 220 EATGSKETLSVDQLVTFLQHQQREEEAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLS 281
Cdd:cd16221   78 TYSNHKDHLDTNDLQRFLEVEQKMAGVTREHCLEIISQFEPCSENKQNGALGIDGFTNYMRS 139

EFh_PI-PLCbeta

cd16200

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

142-283

8.47e-14

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: 69.58 E-value: 8.47e-14

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 142 RHWIHSCLrkaDKNKDNKMSFKelqNFLKELNIQVDDSYARKIFKECD--HSQTDSLEDEEI--ETFYKI---LTQRKEI 214
Cdd:cd16200    2 KLYTKLKL---SVNITGKIPVK---NIIKCFSSDKKRKRVLKALKALGlpDGKNDEIDPEDFtfEKFFKLynkLCPRPDI 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 215 DRTFEEATGSKET-LSVDQLVTFLQHQQREeeagPAL------------ALSLIERYEPSETAKAQRQMTKDGFLMYLLS 281
Cdd:cd16200   76 DEIFKELGGKRKPyLTLEQLVDFLNEEQRD----PRLneilfpfhtkeqAKKLIDKYEPNEKNKKKGQLTLEGFLRYLMS 151


                 ..
gi 160331885 282 AD 283
Cdd:cd16200  152 DE 153

EFh_NorpA_like

cd16212

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

194-283

3.56e-11

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: 61.80 E-value: 3.56e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 194 DSLEDEEI--ETFYKI---LTQRKEIDRTFEEATGSK-ETLSVDQLVTFLQHQQREEEAGPAL--------ALSLIERYE 259
Cdd:cd16212   50 DSIEKEDFtfEKFYALyhkICPRNDIEELFTSITKGKgEHISLAQLINFMNDKQRDPRLNEILyplydekrCTEIIKAYE 129

                         90       100
                 ....*....|....*....|....
gi 160331885 260 PSETAKAQRQMTKDGFLMYLLSAD 283
Cdd:cd16212  130 QNEENIKNKRMSKDGFIRYLMSDE 153

PH_PLC_plant-like

cd13365

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

19-125

4.90e-11

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: 60.38 E-value: 4.90e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885  19 LQALLKGGQLLKVKSNSWRRERFYKLQEDCKT-IWQESRKVMRTPesqlFSIEDIQEVRMGHRTEGLEKFARDVPENRCF 97
Cdd:cd13365    7 ITQLKIGSYLLKYGRRGKPHFRYFWLSPDELTlYWSSPKKGSEKR----VRLSSVSRIIPGQRTVVFKRPPPPGLEEHSF 82

                         90       100
                 ....*....|....*....|....*...
gi 160331885  98 SIVFKDQRNTLDLIAPSPADAQHWVQGL 125
Cdd:cd13365   83 SIIYADGERSLDLTCKDRQEFDTWFTGL 110

EFh_PI-PLCbeta4

cd16211

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

156-283

8.01e-11

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: 60.90 E-value: 8.01e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 156 KDNKMSFKELqnflKELNIQvddsyarkifkecdHSQTDSLEDEEI--ETFYKiLTQ----RKEIDRTFEEATG-SKETL 228
Cdd:cd16211   30 KTEKIVFQSL----KELGLP--------------SGKNDEIEPEAFtfEKFYE-LYHkicpRTDIEELFKKINGdKKDYL 90

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 160331885 229 SVDQLVTFLQHQQREEEAGPAL--------ALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 283
Cdd:cd16211   91 TVDQLISFLNEHQRDPRLNEILfpfydrkrVMQIIETYEVDEEFKKKEQLSSDGFCRYLMSDE 153

EFh_PRIP2

cd16223

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

144-283

9.73e-11

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: 60.31 E-value: 9.73e-11

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 144 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFKECDHSQ----TDSLEDEEIETFYKILTqRKEIDRTFE 219
Cdd:cd16223    1 WLSQMFVEADTDNVGHITLCRAVQFIKNLNPGLKTSKIELKFKELHKSKekggTEVTKEEFIEVFHELCT-RPEIYFLLV 79

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 160331885 220 EATGSKETLSVDQLVTFLQHQQREEEAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 283
Cdd:cd16223   80 QFSSNKEFLDTKDLMMFLEAEQGMAHVTEEISLDIIHKYEPSKEGQEKGWLSLDGFTNYLMSPE 143

EFh_PRIP1

cd16222

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

144-283

3.50e-10

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: 58.72 E-value: 3.50e-10

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 144 WIHSCLRKADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFKECDHSQ---TDSLEDEEIETFYKILTQRKEIDRTFEE 220
Cdd:cd16222    1 WLSAVFEAADVDGYGIMLEDTAVELIKQLNPGIKEAKIRLKFKEIQKSKeklTTRVTEEEFCEAYSELCTRPEVYFLLVQ 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 160331885 221 ATGSKETLSVDQLVTFLQHQQREEEAGPALALSLIERYEPSETAKAQRQMTKDGFLMYLLSAD 283
Cdd:cd16222   81 ISKNKEYLDAKDLMLFLEAEQGMTHITEEMCLDIIRRYEPSQEGRLKGFLGIDGFTQYLLSSE 143

PH_PLC_fungal

cd13360

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

22-131

1.58e-09

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: 56.04 E-value: 1.58e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885  22 LLKGGQLLKVKSNSwRRERFYKLQEDCKTIWQESRKvmrtpESQLFSIEDIQEVRMG-----HRTE-GL-EKFardvpEN 94
Cdd:cd13360    1 LRQGTPLLKVTKKK-KKRILFKLDPESGKITWDSKK-----PSKSLYIDDIKEIRTGedarnYREEfGIsEEF-----ED 69

                         90       100       110       120
                 ....*....|....*....|....*....|....*....|.
gi 160331885  95 RCFSIVFKDQRN----TLDLIAPSPADAQHWVQGLGKIIHH 131
Cdd:cd13360   70 RWITIIYFVPKKnklkTLHLIADTEEDFKLWTTTLEGLVKL 110

C2B_Munc13-like

cd04009

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

630-726

3.05e-09

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: 55.71 E-value: 3.05e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 630 RLNVRVISGQQLPKVNKNKNSivDPKVTVEI--HGVSRDVASRQTAVVTNNgFNPWWDTELEFEVAVPEL----ALVRFV 703
Cdd:cd04009   17 SLRVEILNARNLLPLDSNGSS--DPFVKVELlpRHLFPDVPTPKTQVKKKT-LFPLFDESFEFNVPPEQCsvegALLLFT 93

                         90       100
                 ....*....|....*....|...
gi 160331885 704 VEDYDASSKNDFIGQSTIPLKSL 726
Cdd:cd04009   94 VKDYDLLGSNDFEGEAFLPLNDI 116

COG5038

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

631-729

3.20e-09

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

Pssm-ID: 227371 [Multi-domain] Cd Length: 1227 Bit Score: 60.54 E-value: 3.20e-09

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885  631 LNVRVISGQQLPKVNKNKNSivDPKVTVEIHGVSrdvaSRQTAVVTNNgFNPWWDTELEFEVAVPELALVRFVVEDYDAS 710
Cdd:COG5038  1042 LTIMLRSGENLPSSDENGYS--DPFVKLFLNEKS----VYKTKVVKKT-LNPVWNEEFTIEVLNRVKDVLTINVNDWDSG 1114

                          90
                  ....*....|....*....
gi 160331885  711 SKNDFIGQSTIPLKSLKQG 729
Cdd:COG5038  1115 EKNDLLGTAEIDLSKLEPG 1133

C2B_Synaptotagmin

cd00276

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

627-732

6.49e-09

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: 54.90 E-value: 6.49e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 627 TPKRLNVRVISGQQLPKVNKNKNSivDPKVTVEIHGVSRDVASRQTAVVTNNgFNPWWDTELEFEVAVPELALV--RFVV 704
Cdd:cd00276   12 TAERLTVVVLKARNLPPSDGKGLS--DPYVKVSLLQGGKKLKKKKTSVKKGT-LNPVFNEAFSFDVPAEQLEEVslVITV 88

                         90       100
                 ....*....|....*....|....*...
gi 160331885 705 EDYDASSKNDFIGQSTIPLKSLKQGYRH 732
Cdd:cd00276   89 VDKDSVGRNEVIGQVVLGPDSGGEELEH 116

EFh_PI-PLCbeta1

cd16208

EF-hand motif found in phosphoinositide phospholipase C beta 1 (PI-PLC-beta1); PI-PLC-beta1, ...

191-279

9.85e-09

EF-hand motif found in phosphoinositide phospholipase C beta 1 (PI-PLC-beta1); PI-PLC-beta1, also termed 1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1, or PLC-154, or phospholipase C-I (PLC-I), or phospholipase C-beta-1 (PLC-beta1), is expressed at highest levels in specific regions of the brain, as well as in the cardiovascular system. It has two splice variants, PI-PLC-beta1a and PI-PLC-beta1b, both of which are present within the nucleus. Nuclear PI-PLC-beta1 is a key molecule for nuclear inositide signaling, where it plays a role in cell cycle progression, proliferation and differentiation. It also contributes to generate cell-specific Ca2+ signals evoked by G protein-coupled receptor stimulation. PI-PLC-beta1 acts as an effector and a GTPase activating protein (GAP) specifically activated by the heterotrimeric G protein alpha q subunits through their C2 domain and long C-terminal extension. It regulates neuronal activity in the cerebral cortex and hippocampus, and has been implicated for participations in diverse critical functions related to forebrain diseases such as schizophrenia. It may play an important role in maintenance of the status epilepticus, and in osteosarcoma-related signal transduction pathways. PI-PLC-beta1 also functions as a regulator of erythropoiesis in kinamycin F, a potent inducer of gamma-globin production in K562 cells. The G protein activation and the degradation of PI-PLC-beta1 can be regulated by the interaction of alpha-synuclein. As a result, it may reduce cell damage under oxidative stress. Moreover, PI-PLC-beta1 works as a new intermediate in the HIV-1 gp120-triggered phosphatidylcholine-specific phospholipase C (PC-PLC)-driven signal transduction pathway leading to cytoplasmic CCL2 secretion in macrophages. PI-PLC-beta1 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: 320038 Cd Length: 151 Bit Score: 54.88 E-value: 9.85e-09

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 191 SQTDS--LED---EEIETFYKILTQRKEIDRTFEE-ATGSKETLSVDQLVTFLQHQQREEEAG--------PALALSLIE 256
Cdd:cd16208   45 SRNDSipQEDftpEVYRVFLNNLCPRPEIDHIFSEfGAKSKPYLSVDQMTEFINSKQRDPRLNeilypplkQEQVQQLIE 124

                         90       100
                 ....*....|....*....|...
gi 160331885 257 RYEPSETAKAQRQMTKDGFLMYL 279
Cdd:cd16208  125 KYEPNSTLAKKGQISVDGFMRYL 147

smart00233

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

22-130

4.68e-08

Pssm-ID: 214574 [Multi-domain] Cd Length: 102 Bit Score: 51.40 E-value: 4.68e-08

                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885    22 LLKGGQLLKVKS--NSWRRERFYKLQEDCKTIWQESRKVMRTPESQLFSIEDIQeVRMGHRTEglekfarDVPENRCFSI 99
Cdd:smart00233   1 VIKEGWLYKKSGggKKSWKKRYFVLFNSTLLYYKSKKDKKSYKPKGSIDLSGCT-VREAPDPD-------SSKKPHCFEI 72

                           90       100       110
                   ....*....|....*....|....*....|.
gi 160331885   100 VFKDqRNTLDLIAPSPADAQHWVQGLGKIIH 130
Cdd:smart00233  73 KTSD-RKTLLLQAESEEEREKWVEALRKAIA 102

EFh_PI-PLCbeta3

cd16210

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

184-279

1.67e-07

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: 51.46 E-value: 1.67e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 184 IFKECDHSQTDSLEDEEIETFYKILTQRKEIDRTFEE-ATGSKETLSVDQLVTFLQHQQREEEAG--------PALALSL 254
Cdd:cd16210   43 KFNRSESIKPDEFTLEIFERFLNKLCLRPDIDKILLEiGAKGKPYLTLEQLMDFINQKQRDPRLNevlypplrPSQVRQL 122

                         90       100
                 ....*....|....*....|....*
gi 160331885 255 IERYEPSETAKAQRQMTKDGFLMYL 279
Cdd:cd16210  123 IEKYEPNQQFLERDQMSMEGFSRYL 147

C2D_Tricalbin-like

cd04040

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

631-726

1.81e-07

C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the fifth C2 repeat, C2E, and has a type-II topology.

Pssm-ID: 176005 [Multi-domain] Cd Length: 115 Bit Score: 50.26 E-value: 1.81e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 631 LNVRVISGQQLPKVNKNKNSivDPKVTVEIHGVSrdVAsrQTAVVTNNgFNPWWDTELEFEVAVPELALVRFVVEDYDAS 710
Cdd:cd04040    1 LTVDVISAENLPSADRNGKS--DPFVKFYLNGEK--VF--KTKTIKKT-LNPVWNESFEVPVPSRVRAVLKVEVYDWDRG 73

                         90
                 ....*....|....*.
gi 160331885 711 SKNDFIGQSTIPLKSL 726
Cdd:cd04040   74 GKDDLLGSAYIDLSDL 89

C2B_RasA1_RasA4

cd04025

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

630-728

4.52e-07

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: 49.41 E-value: 4.52e-07

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 630 RLNVRVISGQQLPKvnKNKNSIVDPKVTVEIHGvsrdvASRQTAVVTNNGFnPWWDTELEFEVAVPELALVRFVVEDYDA 709
Cdd:cd04025    1 RLRCHVLEARDLAP--KDRNGTSDPFVRVFYNG-----QTLETSVVKKSCY-PRWNEVFEFELMEGADSPLSVEVWDWDL 72

                         90
                 ....*....|....*....
gi 160331885 710 SSKNDFIGQSTIPLKSLKQ 728
Cdd:cd04025   73 VSKNDFLGKVVFSIQTLQQ 91

C2B_Synaptotagmin-7

cd08405

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

627-725

1.52e-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: 48.18 E-value: 1.52e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 627 TPKRLNVRVISGQQLPKVNKNKNSivDPKVTVEIHGVSRDVASRQTAVVTNNgFNPWWDTELEFEVAVP---ELALVrFV 703
Cdd:cd08405   13 TANRITVNIIKARNLKAMDINGTS--DPYVKVWLMYKDKRVEKKKTVIKKRT-LNPVFNESFIFNIPLErlrETTLI-IT 88

                         90       100
                 ....*....|....*....|..
gi 160331885 704 VEDYDASSKNDFIGQSTIPLKS 725
Cdd:cd08405   89 VMDKDRLSRNDLIGKIYLGWKS 110

C2B_RasGAP

cd08675

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

631-728

2.09e-06

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

Pssm-ID: 176057 [Multi-domain] Cd Length: 137 Bit Score: 47.75 E-value: 2.09e-06

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 631 LNVRVISGQQLPKVNkNKNSivDPKVTVEIHGVSRDVASRqTAVV--TNNgfnPWWDTELEFEVAVPE------------ 696
Cdd:cd08675    1 LSVRVLECRDLALKS-NGTC--DPFARVTLNYSSKTDTKR-TKVKkkTNN---PRFDEAFYFELTIGFsyekksfkveee 73

                         90       100       110
                 ....*....|....*....|....*....|....*
gi 160331885 697 -LALVRFVVEDYDAS--SKNDFIGQSTIPLKSLKQ 728
Cdd:cd08675   74 dLEKSELRVELWHASmvSGDDFLGEVRIPLQGLQQ 108

cd00821

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

24-125

1.94e-05

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: 43.69 E-value: 1.94e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885  24 KGGQLLKVKSNSWR--RERFYKLQEDCKTIWQESRKVMRTPEsQLFSIEDIQEVRMGHRTEglekfardvpENRCFSIVF 101
Cdd:cd00821    1 KEGYLLKRGGGGLKswKKRWFVLFEGVLLYYKSKKDSSYKPK-GSIPLSGILEVEEVSPKE----------RPHCFELVT 69

                         90       100
                 ....*....|....*....|....
gi 160331885 102 KDQRnTLDLIAPSPADAQHWVQGL 125
Cdd:cd00821   70 PDGR-TYYLQADSEEERQEWLKAL 92

C2_ArfGAP

cd04038

C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating ...

631-735

3.29e-05

C2 domain present in Arf GTPase Activating Proteins (GAP); ArfGAP is a GTPase activating protein which regulates the ADP ribosylation factor Arf, a member of the Ras superfamily of GTP-binding proteins. The GTP-bound form of Arf is involved in Golgi morphology and is involved in recruiting coat proteins. ArfGAP is responsible for the GDP-bound form of Arf which is necessary for uncoating the membrane and allowing the Golgi to fuse with an acceptor compartment. These proteins contain an N-terminal ArfGAP domain containing the characteristic zinc finger motif (Cys-x2-Cys-x(16,17)-x2-Cys) and C-terminal C2 domain. C2 domains were first identified in Protein Kinase C (PKC). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176003 [Multi-domain] Cd Length: 145 Bit Score: 44.62 E-value: 3.29e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 631 LNVRVISGQQLpkVNKNKNSiVDPKVTVEIhgvsrDVASRQTAVVTNNgFNPWWDTELEFEVAVPElALVRFVVEDYDAS 710
Cdd:cd04038    4 LKVRVVRGTNL--AVRDFTS-SDPYVVLTL-----GNQKVKTRVIKKN-LNPVWNEELTLSVPNPM-APLKLEVFDKDTF 73

                         90       100
                 ....*....|....*....|....*...
gi 160331885 711 SKNDFIGQSTI---PLKSLKQGYRHIHL 735
Cdd:cd04038   74 SKDDSMGEAEIdlePLVEAAKLDHLRDT 101

EFh

cd00051

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

149-189

4.49e-05

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: 41.76 E-value: 4.49e-05

                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*
gi 160331885 149 LRKA----DKNKDNKMSFKELQNFLKELNIQVDDSYARKIFKECD 189
Cdd:cd00051    2 LREAfrlfDKDGDGTISADELKAALKSLGEGLSEEEIDEMIREVD 46

C2A_Synaptotagmin-like

cd04024

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

631-726

4.99e-05

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

Pssm-ID: 175990 [Multi-domain] Cd Length: 128 Bit Score: 43.57 E-value: 4.99e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 631 LNVRVISGQQLPKVNKNKNSIVDPKVTVEIHgvsrdvASRQTAVVTNNGFNPWWDTELEFEVAVPELALVRFVVEDYDAS 710
Cdd:cd04024    3 LRVHVVEAKDLAAKDRSGKGKSDPYAILSVG------AQRFKTQTIPNTLNPKWNYWCEFPIFSAQNQLLKLILWDKDRF 76

                         90
                 ....*....|....*.
gi 160331885 711 SKNDFIGQSTIPLKSL 726
Cdd:cd04024   77 AGKDYLGEFDIALEEV 92

PH_12

pfam16457

Pleckstrin homology domain;

19-125

7.33e-05

Pleckstrin homology domain;

Pssm-ID: 465123 [Multi-domain] Cd Length: 128 Bit Score: 43.02 E-value: 7.33e-05

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885   19 LQALLKGGQLLKVKSNS-WRRERFYKLQEDCKTIW----QESRKVMRTPESQLFSIE--DIQEVRMGHRTE---GLEKFA 88
Cdd:pfam16457   6 LNCLLEGAWFPKVRGRRrKKKYRFCRLSPNRKVLHygdfEEKPTVDPSLESLPEKIDlsDIKEVVTGKECPhvrESGKKS 85

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 160331885   89 RDVPENRCFSIVF-KDQRNTLDLIAPSPADAQHWVQGL 125
Cdd:pfam16457  86 KKTSSTLAFSLIYgADEYELLDFVAPSESVAAIWLDGL 123

C2_putative_Elicitor-responsive_gene

cd04049

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

631-726

8.11e-05

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

Pssm-ID: 176014 [Multi-domain] Cd Length: 124 Bit Score: 42.70 E-value: 8.11e-05

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 631 LNVRVISGQQLpkvnKNKNSIVDPKVTVEIHGVSRDvasRQTAVVTNNGFNPWWDTELEFEVAVPELALV---RFVVEDY 707
Cdd:cd04049    3 LEVLLISAKGL----QDTDFLGKIDPYVIIQCRTQE---RKSKVAKGDGRNPEWNEKFKFTVEYPGWGGDtklILRIMDK 75

                         90
                 ....*....|....*....
gi 160331885 708 DASSKNDFIGQSTIPLKSL 726
Cdd:cd04049   76 DNFSDDDFIGEATIHLKGL 94

EFh_PI-PLCbeta2

cd16209

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

202-279

1.10e-04

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: 42.94 E-value: 1.10e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 202 ETFYKILTQRKEIDRTFEE-ATGSKETLSVDQLVTFLQHQQREEE--------AGPALALSLIERYEPSETAKAQRQMTK 272
Cdd:cd16209   61 KTFLMQLCPRPEIDEIFTSyHAKAKPYMTKEHLTKFINKKQRDSRlneelfppARPDQVQGLIEKYEPSGINAQRGQLSP 140


                 ....*..
gi 160331885 273 DGFLMYL 279
Cdd:cd16209  141 EGMVWFL 147

C2A_RIM1alpha

cd04031

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

629-723

1.19e-04

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: 42.23 E-value: 1.19e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 629 KRLNVRVISGQQLPKvnKNKNSIVDPKVTVEIHGVSRDVASRQTAVVTNNgFNPWWDTELEFEVAVPELALVRFV---VE 705
Cdd:cd04031   16 SQLIVTVLQARDLPP--RDDGSLRNPYVKVYLLPDRSEKSKRRTKTVKKT-LNPEWNQTFEYSNVRRETLKERTLevtVW 92

                         90
                 ....*....|....*...
gi 160331885 706 DYDASSKNDFIGQSTIPL 723
Cdd:cd04031   93 DYDRDGENDFLGEVVIDL 110

C2B_Synaptotagmin-17

cd08410

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

630-721

1.62e-04

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: 42.18 E-value: 1.62e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 630 RLNVRVISGQQLPKVNKNKNSivDPKVTVE-IHGVsRDVASRQTAVVTNNgFNPWWDTELEFEVAVPELALVR--FVVED 706
Cdd:cd08410   15 RLNVDIIRAKQLLQTDMSQGS--DPFVKIQlVHGL-KLIKTKKTSCMRGT-IDPFYNESFSFKVPQEELENVSlvFTVYG 90

                         90
                 ....*....|....*
gi 160331885 707 YDASSKNDFIGQSTI 721
Cdd:cd08410   91 HNVKSSNDFIGRIVI 105

C2A_Synaptotagmin-8

cd08387

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

631-726

1.72e-04

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

Pssm-ID: 176033 [Multi-domain] Cd Length: 124 Bit Score: 42.01 E-value: 1.72e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 631 LNVRVISGQQLPKvnKNKNSIVDPKVTVE-IHGVSRDVASRqtavVTNNGFNPWWDTELEFEVAVPELA--LVRFVVEDY 707
Cdd:cd08387   18 LNVKLIQARNLQP--RDFSGTADPYCKVRlLPDRSNTKQSK----IHKKTLNPEFDESFVFEVPPQELPkrTLEVLLYDF 91

                         90
                 ....*....|....*....
gi 160331885 708 DASSKNDFIGQSTIPLKSL 726
Cdd:cd08387   92 DQFSRDECIGVVELPLAEV 110

EFh_PI-PLCgamma

cd16201

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

149-243

1.74e-04

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: 42.17 E-value: 1.74e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 149 LRK----ADKNKDNKMSFKELQNFLKELNIQVDDSYARKIFKECDHSQTDSLEDEEIETFYKILTQ-RKEIDRTFEEATG 223
Cdd:cd16201    2 LRKefysMDRTRRETVTLKDLKAFLPRVNCKISTNKLREKFQEVDTRRRGELGFDDFAQLYHKLMFdQKIIEDFFKKYSY 81

                         90       100
                 ....*....|....*....|..
gi 160331885 224 SKE--TLSVDQLVTFLQHQQRE 243
Cdd:cd16201   82 SSDgqTVTLEDFQRFLLEEQKE 103

C2A_Synaptotagmin-15-17

cd08390

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

629-724

3.49e-04

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: 41.09 E-value: 3.49e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 629 KRLNVRVISGQQLPKVNKNKNSiVDPKVTVEIHGVSRDvaSRQTaVVTNNGFNPWWDTELEFEVAVPEL--ALVRFVVED 706
Cdd:cd08390   14 EQLTVSLIKARNLPPRTKDVAH-CDPFVKVCLLPDERR--SLQS-KVKRKTQNPNFDETFVFQVSFKELqrRTLRLSVYD 89

                         90
                 ....*....|....*...
gi 160331885 707 YDASSKNDFIGQSTIPLK 724
Cdd:cd08390   90 VDRFSRHCIIGHVLFPLK 107

C2_PKC_alpha_gamma

cd04026

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

626-726

3.72e-04

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

Pssm-ID: 175992 [Multi-domain] Cd Length: 131 Bit Score: 41.09 E-value: 3.72e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 626 WTPKRLNVRVISGQQLPKVNKNKNSivDPKVTVEIHGVSRDVASRQTAVVTNNgFNPWWDTELEFEVAvPELALVRFVVE 705
Cdd:cd04026   10 VKDNKLTVEVREAKNLIPMDPNGLS--DPYVKLKLIPDPKNETKQKTKTIKKT-LNPVWNETFTFDLK-PADKDRRLSIE 85

                         90       100
                 ....*....|....*....|...
gi 160331885 706 --DYDASSKNDFIGQSTIPLKSL 726
Cdd:cd04026   86 vwDWDRTTRNDFMGSLSFGVSEL 108

C2B_Munc13

cd04027

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

630-726

4.10e-04

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

Pssm-ID: 175993 [Multi-domain] Cd Length: 127 Bit Score: 41.01 E-value: 4.10e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 630 RLNVRVISGQQLpkVNKNKNSIVDPKVTVEIHGVSRdvasrQTAVVTNNgFNPWWDTELEFEV-AVPELALVRFVVEDYD 708
Cdd:cd04027    2 KISITVVCAQGL--IAKDKTGTSDPYVTVQVGKTKK-----RTKTIPQN-LNPVWNEKFHFEChNSSDRIKVRVWDEDDD 73

                         90       100
                 ....*....|....*....|....*..
gi 160331885 709 ASSK---------NDFIGQSTIPLKSL 726
Cdd:cd04027   74 IKSRlkqkftresDDFLGQTIIEVRTL 100

pfam00169

PH domain; PH stands for pleckstrin homology.

22-130

4.35e-04

PH domain; PH stands for pleckstrin homology.

Pssm-ID: 459697 [Multi-domain] Cd Length: 105 Bit Score: 40.24 E-value: 4.35e-04

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885   22 LLKGGQLLK---VKSNSWRReRFYKLQEDCKTIWQESRKVMRTPESQLFSIEDIQEVRMGHRTEGLEKFardvpenrCFS 98
Cdd:pfam00169   1 VVKEGWLLKkggGKKKSWKK-RYFVLFDGSLLYYKDDKSGKSKEPKGSISLSGCEVVEVVASDSPKRKF--------CFE 71

                          90       100       110
                  ....*....|....*....|....*....|....
gi 160331885   99 IVFKDQRN--TLDLIAPSPADAQHWVQGLGKIIH 130
Cdd:pfam00169  72 LRTGERTGkrTYLLQAESEEERKDWIKAIQSAIR 105

C2_KIAA0528-like

cd08688

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

631-726

4.90e-04

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: 40.37 E-value: 4.90e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 631 LNVRVISGQQLPKVNKNKNSiVDPKVTVEIhgvsrDVASRQTAVVTNNgFNPWWDTElEFEVAVPELAL----VRFVVED 706
Cdd:cd08688    1 LKVRVVAARDLPVMDRSSDL-TDAFVEVKF-----GSTTYKTDVVKKS-LNPVWNSE-WFRFEVDDEELqdepLQIRVMD 72

                         90       100
                 ....*....|....*....|
gi 160331885 707 YDASSKNDFIGQSTIPLKSL 726
Cdd:cd08688   73 HDTYSANDAIGKVYIDLNPL 92

C2B_Synaptotagmin-1

cd08402

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

627-732

5.02e-04

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: 40.85 E-value: 5.02e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 627 TPKRLNVRVISGQQLPKVNKNKNSivDPKVTVEIHGVSRDVASRQTAVvTNNGFNPWWDTELEFEVAVPELALVRFVVE- 705
Cdd:cd08402   13 TAGKLTVVILEAKNLKKMDVGGLS--DPYVKIHLMQNGKRLKKKKTTI-KKRTLNPYYNESFSFEVPFEQIQKVHLIVTv 89

                         90       100
                 ....*....|....*....|....*...
gi 160331885 706 -DYDASSKNDFIGQSTIPLKSLKQGYRH 732
Cdd:cd08402   90 lDYDRIGKNDPIGKVVLGCNATGAELRH 117

C2C_MCTP_PRT

cd08377

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...

631-736

5.49e-04

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. The cds in this family contain multiple C2 domains as well as a C-terminal PRT domain. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 176023 [Multi-domain] Cd Length: 119 Bit Score: 40.36 E-value: 5.49e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 631 LNVRVISGQQLPKVNKNKNSivDPKVTVEIhgvsrdVASR-QTAVVTNNgFNPWWDTELEFEV----AVPELAlvrfvVE 705
Cdd:cd08377    3 LQVKVIRASGLAAADIGGKS--DPFCVLEL------VNARlQTHTIYKT-LNPEWNKIFTFPIkdihDVLEVT-----VY 68

                         90       100       110
                 ....*....|....*....|....*....|.
gi 160331885 706 DYDASSKNDFIGQSTIPLKSLKQGYRHIHLL 736
Cdd:cd08377   69 DEDKDKKPEFLGKVAIPLLSIKNGERKWYAL 99

C2_C21orf25-like

cd08678

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

671-729

6.54e-04

C2 domain found in the Human chromosome 21 open reading frame 25 (C21orf25) protein; The members in this cd are named after the Human C21orf25 which contains a single C2 domain. Several other members contain a C1 domain downstream of the C2 domain. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 176060 [Multi-domain] Cd Length: 126 Bit Score: 40.43 E-value: 6.54e-04

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|....*....
gi 160331885 671 QTAVVTNNGfNPWWDTELEFEVAvPELALVRFVVEDYDASSKNDFIGQSTIPLKSLKQG 729
Cdd:cd08678   34 QSSTQKNTS-NPFWDEHFLFELS-PNSKELLFEVYDNGKKSDSKFLGLAIVPFDELRKN 90

PI-PLCc_bacteria_like

cd08557

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

297-417

6.98e-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: 42.08 E-value: 6.98e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 297 DMDQPLSHYLVSSSHNTY-----LLEDQLTGPSST-EAYIR-ALCKGCRCLELDCWDGPNQEPI-IYHGYTFTSKILFCD 368
Cdd:cd08557    4 LDDLPLSQLSIPGTHNSYaytidGNSPIVSKWSKTqDLSITdQLDAGVRYLDLRVAYDPDDGDLyVCHGLFLLNGQTLED 83

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|...
gi 160331885 369 VVRAIRDYAfKASPY-PVILSLENHCSLEQQRVMA---RHLRTLLGPMLLDRP 417
Cdd:cd08557   84 VLNEVKDFL-DAHPSeVVILDLEHEYGGDNGEDHDeldALLRDVLGDPLYRPP 135

C2E_Ferlin

cd04037

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

632-723

7.10e-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: 40.23 E-value: 7.10e-04

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 632 NVRVISGQQLPkvNKNKNSIVDP--KVTVEIHGVSrdvaSRQTAVVtnNGFNPWWDTELEFEVAVPELALVRFVVEDYDA 709
Cdd:cd04037    3 RVYVVRARNLQ--PKDPNGKSDPylKIKLGKKKIN----DRDNYIP--NTLNPVFGKMFELEATLPGNSILKISVMDYDL 74

                         90
                 ....*....|....
gi 160331885 710 SSKNDFIGQSTIPL 723
Cdd:cd04037   75 LGSDDLIGETVIDL 88

EF-hand_7

pfam13499

EF-hand domain pair;

144-206

8.23e-04

EF-hand domain pair;

Pssm-ID: 463900 [Multi-domain] Cd Length: 67 Bit Score: 38.39 E-value: 8.23e-04

                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 160331885  144 WIHSCLRKADKNKDNKMSFKELQNFLK--ELNIQVDDSYARKIFKECDHSQTDSLEDEEIETFYK 206
Cdd:pfam13499   3 KLKEAFKLLDSDGDGYLDVEELKKLLRklEEGEPLSDEEVEELFKEFDLDKDGRISFEEFLELYS 67

C2_Intersectin

cd08375

C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally ...

630-728

1.23e-03

C2 domain present in Intersectin; A single instance of the C2 domain is located C terminally in the intersectin protein. Intersectin functions as a scaffolding protein, providing a link between the actin cytoskeleton and the components of endocytosis and plays a role in signal transduction. In addition to C2, intersectin contains several additional domains including: Eps15 homology domains, SH3 domains, a RhoGEF domain, and a PH 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. The members here have topology I.

Pssm-ID: 176021 [Multi-domain] Cd Length: 136 Bit Score: 39.68 E-value: 1.23e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 630 RLNVRVISGQQLPKVNKNKNSivDPKVTVeihgvSRDVASRQTAVVTNNgFNPWWDTELEFEVAVPELALVRFVVEDYDA 709
Cdd:cd08375   16 RLMVVIVEGRDLKPCNSNGKS--DPYCEV-----SMGSQEHKTKVVSDT-LNPKWNSSMQFFVKDLEQDVLCITVFDRDF 87

                         90
                 ....*....|....*....
gi 160331885 710 SSKNDFIGQSTIPLKSLKQ 728
Cdd:cd08375   88 FSPDDFLGRTEIRVADILK 106

EFh_HEF_SCGN

cd16178

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

128-206

1.50e-03

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: 41.23 E-value: 1.50e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 128 IIHHSGSMDQQQKLRHWIHSCLRKADKNKDNKMSFKEL-------QNFLkeLNIQVDDSYAR-------KIFKECDHSQT 193
Cdd:cd16178  121 LFLQHKKVITEDKLDEYTDTMMKIFDKNKDGRLDLNDMarilalqENFL--LQFKMDAMSEEerkrdfeKIFAHYDVSKT 198

                         90
                 ....*....|...
gi 160331885 194 DSLEDEEIETFYK 206
Cdd:cd16178  199 GALEGPEVDGFVK 211

C2A_Ferlin

cd08373

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

635-726

1.59e-03

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

Pssm-ID: 176019 [Multi-domain] Cd Length: 127 Bit Score: 39.16 E-value: 1.59e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 635 VISGQQLPkvnkNKNSIVDPKVTVEIHGVSRdvasrQTAVVTNNGfNPWWDTELEFEVA-VPE----LALVrfvVEDYDA 709
Cdd:cd08373    2 VVSLKNLP----GLKGKGDRIAKVTFRGVKK-----KTRVLENEL-NPVWNETFEWPLAgSPDpdesLEIV---VKDYEK 68

                         90
                 ....*....|....*..
gi 160331885 710 SSKNDFIGQSTIPLKSL 726
Cdd:cd08373   69 VGRNRLIGSATVSLQDL 85

C2_NEDD4_NEDD4L

cd04033

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

631-726

1.96e-03

C2 domain present in the Human neural precursor cell-expressed, developmentally down-regulated 4 (NEDD4) and NEDD4-like (NEDD4L/NEDD42); Nedd4 and Nedd4-2 are two of the nine members of the Human Nedd4 family. All vertebrates appear to have both Nedd4 and Nedd4-2 genes. They are thought to participate in the regulation of epithelial Na+ channel (ENaC) activity. They also have identical specificity for ubiquitin conjugating enzymes (E2). Nedd4 and Nedd4-2 are composed of a C2 domain, 2-4 WW domains, and a ubiquitin ligase Hect domain. Their WW domains can bind PPxY (PY) or LPSY motifs, and in vitro studies suggest that WW3 and WW4 of both proteins bind PY motifs in the key substrates, with WW3 generally exhibiting higher affinity. Most Nedd4 family members, especially Nedd4-2, also have multiple splice variants, which might play different roles in regulating their substrates. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.

Pssm-ID: 175999 [Multi-domain] Cd Length: 133 Bit Score: 39.26 E-value: 1.96e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 631 LNVRVISGQQLPKvnKNKNSIVDP--KVTVEIHGVSRDVASRQTAVVTNNgFNPWWDTELEFEVAVPELALVrFVVEDYD 708
Cdd:cd04033    2 LRVKVLAGIDLAK--KDIFGASDPyvKISLYDPDGNGEIDSVQTKTIKKT-LNPKWNEEFFFRVNPREHRLL-FEVFDEN 77

                         90
                 ....*....|....*...
gi 160331885 709 ASSKNDFIGQSTIPLKSL 726
Cdd:cd04033   78 RLTRDDFLGQVEVPLNNL 95

C2C_MCTP_PRT_plant

cd04019

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...

631-726

2.15e-03

C2 domain third repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.

Pssm-ID: 175986 [Multi-domain] Cd Length: 150 Bit Score: 39.19 E-value: 2.15e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 631 LNVRVISGQQLpkVNKNKNSIVDPKVTVEIHGVSRdvasrQTAVVTNNGFNPWWDTELEFEVAVP-ELALVrFVVEDYDA 709
Cdd:cd04019    2 LRVTVIEAQDL--VPSDKNRVPEVFVKAQLGNQVL-----RTRPSQTRNGNPSWNEELMFVAAEPfEDHLI-LSVEDRVG 73

                         90
                 ....*....|....*..
gi 160331885 710 SSKNDFIGQSTIPLKSL 726
Cdd:cd04019   74 PNKDEPLGRAVIPLNDI 90

C2_fungal_Inn1p-like

cd08681

C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 ...

631-724

3.14e-03

C2 domain found in fungal Ingression 1 (Inn1) proteins; Saccharomyces cerevisiae Inn1 associates with the contractile actomyosin ring at the end of mitosis and is needed for cytokinesis. The C2 domain of Inn1, located at the N-terminus, is required for ingression of the plasma membrane. The C-terminus is relatively unstructured and contains eight PXXP motifs that are thought to mediate interaction of Inn1 with other proteins with SH3 domains in the cytokinesis proteins Hof1 (an F-BAR protein) and Cyk3 (whose overexpression can restore primary septum formation in Inn1Delta cells) as well as recruiting Inn1 to the bud-neck by binding to Cyk3. Inn1 and Cyk3 appear to cooperate in activating chitin synthase Chs2 for primary septum formation, which allows coordination of actomyosin ring contraction with ingression of the cleavage furrow. It is thought that the C2 domain of Inn1 helps to preserve the link between the actomyosin ring and the plasma membrane, contributing both to membrane ingression, as well as to stability of the contracting ring. Additionally, Inn1 might induce curvature of the plasma membrane adjacent to the contracting ring, thereby promoting ingression of the membrane. It has been shown that the C2 domain of human synaptotagmin induces curvature in target membranes and thereby contributes to fusion of these membranes with synaptic vesicles. 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 synaptotagmin1. 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: 176063 [Multi-domain] Cd Length: 118 Bit Score: 38.00 E-value: 3.14e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 631 LNVRVISGQQLPkvNKNKNSIVDPKVTVEIHGVSRdvasrQTAVVTNNGFNPWWDTELEFEV---AVPELALVRFVvedy 707
Cdd:cd08681    3 LVVVVLKARNLP--NKRKLDKQDPYCVLRIGGVTK-----KTKTDFRGGQHPEWDEELRFEItedKKPILKVAVFD---- 71

                         90
                 ....*....|....*..
gi 160331885 708 DASSKNDFIGQSTIPLK 724
Cdd:cd08681   72 DDKRKPDLIGDTEVDLS 88

C2B_Synaptotagmin-4

cd08404

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

627-740

3.50e-03

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: 38.56 E-value: 3.50e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 627 TPKRLNVRVISGQQLPKVNKNKNSivDPKVTVEIHGVSRDVASRQTAVvTNNGFNPWWDTELEFEVAVPEL--ALVRFVV 704
Cdd:cd08404   13 TTNRLTVVVLKARHLPKMDVSGLA--DPYVKVNLYYGKKRISKKKTHV-KKCTLNPVFNESFVFDIPSEELedISVEFLV 89

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 160331885 705 EDYDASSKNDFIGQSTIPLKSLKQGYRHIHLLSKNG 740
Cdd:cd08404   90 LDSDRVTKNEVIGRLVLGPKASGSGGHHWKEVCNPP 125

EFh_HEF

cd15902

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

139-215

5.27e-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: 5.27e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 139 QKLRHWIHSCLRKADKNKDNKMSFKEL-------QNFLKELNIQVDDSYAR----KIFKECDHSQTDSLEDEEIETFYKI 207
Cdd:cd15902  130 PKLDEYTKLILKEFDANKDGKLELDEMakllpvqENFLLKFQILGAMDLTKedfeKVFEHYDKDNNGVIEGNELDALLKD 209

                         90
                 ....*....|
gi 160331885 208 L--TQRKEID 215
Cdd:cd15902  210 LleKNKADID 219

C2_Munc13_fungal

cd04043

C2 domain in Munc13 (mammalian uncoordinated) proteins; fungal group; C2-like domains are ...

633-723

6.29e-03

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

Pssm-ID: 176008 [Multi-domain] Cd Length: 126 Bit Score: 37.63 E-value: 6.29e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 633 VRVISGQQLPKvnKNKNSIVDPKVTVEIHGVSRDVASrqTAVVTNNgFNPWWDTELEFEVAVPELALVRFVVEDYDASSK 712
Cdd:cd04043    5 IRIVRAENLKA--DSSNGLSDPYVTLVDTNGKRRIAK--TRTIYDT-LNPRWDEEFELEVPAGEPLWISATVWDRSFVGK 79

                         90
                 ....*....|.
gi 160331885 713 NDFIGQSTIPL 723
Cdd:cd04043   80 HDLCGRASLKL 90

C2B_RasA3

cd04010

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

630-728

6.87e-03

C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of GTPase activating protein 1 (GAP1), a Ras-specific GAP, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA3 contains an N-terminal C2 domain, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.

Pssm-ID: 175977 [Multi-domain] Cd Length: 148 Bit Score: 37.76 E-value: 6.87e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 630 RLNVRVISGQQLPKVNKNknsiVDPKVTVEIHGVSRDVASRQTAVV--TNNgfnPWWDTELEFEVAVPELALVR-FVVED 706
Cdd:cd04010    1 KLSVRVIECSDLALKNGT----CDPYASVTLIYSNKKQDTKRTKVKkkTNN---PQFDEAFYFDVTIDSSPEKKqFEMPE 73

                         90       100       110
                 ....*....|....*....|....*....|....*.
gi 160331885 707 YDAS--------------SKNDFIGQSTIPLKSLKQ 728
Cdd:cd04010   74 EDAEklelrvdlwhasmgGGDVFLGEVRIPLRGLDL 109

C2A_C2C_Synaptotagmin_like

cd08391

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

631-730

7.03e-03

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

Pssm-ID: 176037 [Multi-domain] Cd Length: 121 Bit Score: 37.27 E-value: 7.03e-03

                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 160331885 631 LNVRVISGQQLPKVNKNKNSIV----DPKVTVEihgvsrdVASR--QTAVVTNNgFNPWWDtELeFEVAVPELALVRFVV 704
Cdd:cd08391    3 LRIHVIEAQDLVAKDKFVGGLVkgksDPYVIVR-------VGAQtfKSKVIKEN-LNPKWN-EV-YEAVVDEVPGQELEI 72

                         90       100
                 ....*....|....*....|....*...
gi 160331885 705 EDYDAS-SKNDFIGQSTIPLKS-LKQGY 730
Cdd:cd08391   73 ELFDEDpDKDDFLGRLSIDLGSvEKKGF 100

C2B_Rabphilin_Doc2

cd08384

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

668-717

7.21e-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: 37.33 E-value: 7.21e-03

                         10        20        30        40        50
                 ....*....|....*....|....*....|....*....|....*....|..
gi 160331885 668 ASRQTAVVTNNGFNPWWDTELEFEVAVPELA--LVRFVVEDYDASSKNDFIG 717
Cdd:cd08384   49 KSKHKTQVKKKTLNPEFNEEFFYDIKHSDLAkkTLEITVWDKDIGKSNDYIG 100

PH_PLC_gamma

cd13362

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

69-125

7.53e-03

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: 37.26 E-value: 7.53e-03

                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 160331885  69 IEDIQEVRMGHRTEGLEKF---ARDVPENRCFSIVFKDQ--RNTLDLIAPSPADAQHWVQGL 125
Cdd:cd13362   46 IREIKEIRPGKNSKDFERWpdeAKKLDPSCCFVILYGTEfrLKTLSVAATSEEECDMWIKGL 107

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