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Conserved domains on  [gi|157786960|ref|NP_001099421|]
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phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta [Rattus norvegicus]

Protein Classification

phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta( domain architecture ID 10466611)

phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit beta catalyzes the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) and PtdIns4P with a preference for PtdIns

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 974-1327 0e+00

Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II beta isoform, PI3K-C2beta, contributes to the migration and survival of cancer cells. It regulates Rac activity and impacts membrane ruffling, cell motility, and cadherin-mediated cell-cell adhesion. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


:

Pssm-ID: 119421 [Multi-domain]  Cd Length: 354  Bit Score: 737.97  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  974 REEFNRQCWLVNTLAKLAQQVREATPSARQGILRAGLEEVRQFFALNGSCRLPLSPSLLVKGIVPRDCSYFNSNAVPLKL 1053
Cdd:cd00895     1 REEFDRQCWLVNVLAKLAQQVREAAPSARQGILREGLEEVKQFFSINGSCRLPLSPSLLVKGIVPRDCSYFNSNAVPLKL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1054 AFQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGKGMVEMIPNAETLRKIQVEHG 1133
Cdd:cd00895    81 SFQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMNKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEHG 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1134 VTGSFKDRPLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYILGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGN 1213
Cdd:cd00895   161 VTGSFKDRPLADWLQKHNPTEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGN 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1214 IKRDRAPFVFTSDMAYVINGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQ 1293
Cdd:cd00895   241 IKRDRAPFVFTSDMAYVINGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQ 320

                         330       340       350
                  ....*....|....*....|....*....|....
gi 157786960 1294 DTEANATTYFTRLIESSLGSVATKLNFFIHNLAQ 1327
Cdd:cd00895   321 DTEADATTYFTRLIESSLGSVATKLNFFIHNLAQ 354
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
 800-968 2.39e-91

Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, class II PI3-kinases phosphorylate phosphoinositol (PtdIns), PtdIns(4)-phosphate, but not PtdIns(4,5)-bisphosphate. They are larger, having a C2 domain at the C-terminus.


:

Pssm-ID: 238441  Cd Length: 169  Bit Score: 293.21  E-value: 2.39e-91
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  800 EEDQRKLKDITQKESLYWLSDADKKQLWEKRYYCHTEVSSLPLVLASAPSWEWACLPDIYALLQQWTHMNHQDALGLLHA 879
Cdd:cd00869     1 IETQEKLLDLIQKQSTYTLSTEDKDLLWEKRLYCTNEPNALPLVLASAPSWDWANLMDVYQLLHQWAPLRPLIALELLLP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  880 TFPDQEVRRMAVQWIGSLSDAELLDYLPQLVQALKYECYLDSPLVRFLLKRAISDLRVTHYFFWLLKDSLKDSQFSIRYQ 959
Cdd:cd00869    81 KFPDQEVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALDDCYFSSAYQ 160


                  ....*....
gi 157786960  960 YLLAALLCC 968
Cdd:cd00869   161 DLGAALRCQ 169
PX_PI3K_C2_beta cd07290
The phosphoinositide binding Phox Homology Domain of the Beta Isoform of Class II ...
 1356-1464 1.70e-74

The phosphoinositide binding Phox Homology Domain of the Beta Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II beta isoform, PI3K-C2beta, contributes to the migration and survival of cancer cells. It regulates Rac activity and impacts membrane ruffling, cell motility, and cadherin-mediated cell-cell adhesion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


:

Pssm-ID: 132823  Cd Length: 109  Bit Score: 242.52  E-value: 1.70e-74
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1356 DVFLCRHEKVFHPSKGYIYVVKVMRENAHEATYIQRTFEEFQELHNKLRLLFPSSFLPSFPSRFVIGRSRGEAVAERRKE 1435
Cdd:cd07290     1 DVFLCRHESTFNPSKGYAYVVKVQREGHKEATFVQRTFEEFQELHNKLRLLFPSSKLPSFPSRFVIGRSRGEAVAERRKE 80

                          90       100
                  ....*....|....*....|....*....
gi 157786960 1436 ELNGYIWHLIHAAPEVAECDLVYTFFHPL 1464
Cdd:cd07290    81 ELNGYIWHLIHAPPEVAECDLVYTFFHPL 109
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 609-781 4.20e-74

C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. Class II PIK3s act downstream of receptors for growth factors, integrins, and chemokines. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. 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: 175979  Cd Length: 171  Bit Score: 243.80  E-value: 4.20e-74
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  609 QEACHFSGALAFTVYGTHRIPIIWATSYEEFYLSCSLSHGGKELCSPLQTRRAHFSKYLFHLIIWDQQICFPVQVNRLPR 688
Cdd:cd04012     1 REASTVTDLLSVTVSSLHRIPPTWVQSFEDFYLSCSLYHGGRLLCSPVTTKPVKITKSFFPRVVWDEWIEFPIPVCQLPR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  689 ETLLCATLYALPIPPPGSSseaNKQKRVPEALGWVTTPLFNFRQVLTCGRKLLGLWPATQENSSARWSAPNFHQPDSVIL 768
Cdd:cd04012    81 ESRLVLTLYGTTSSPDGGS---NKQRMGPEELGWVSLPLFDFRGVLRQGSLLLGLWPPSKDNPLGPAPPPLFEQPDRVIL 157

                         170
                  ....*....|...
gi 157786960  769 QIDFPTSAFDIKF 781
Cdd:cd04012   158 QIDFPSSAFDVIF 170
C2B_PI3K_class_II cd08381
C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are ...
 1492-1614 2.35e-71

C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. 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: 176027 [Multi-domain]  Cd Length: 122  Bit Score: 234.11  E-value: 2.35e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1492 GGEVKLSISYKNNKLFIMVMHIRGLqPLQDGSDPDPYVKIYLLPDPQKATKRKTKVARKTCNPTYNEMLVYDGIPKGDLQ 1571
Cdd:cd08381     1 GGQVKLSISYKNGTLFVMVMHAKNL-PLLDGSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDGLPVEDLQ 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 157786960 1572 QRELQLSVLSEQGFWENVLLGEVHIRLRELDLAQEKTGWFALG 1614
Cdd:cd08381    80 QRVLQVSVWSHDSLVENEFLGGVCIPLKKLDLSQETEKWYPLG 122
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 363-465 6.48e-32

PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding pfam00788 domains (unpublished observation).


:

Pssm-ID: 395642  Cd Length: 106  Bit Score: 120.48  E-value: 6.48e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960   363 TVTPSPEHL--GDEVNLKVTVLCDSLREPLTFTCNCSSTVDLLIYQTLCYTHDELREVDVG-DFVLKPCGLEEFLQNKHA 439
Cdd:pfam00794    1 ASTVSPEPLpkLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVTdDYVLKVCGRDEYLLGDHP 80

                           90       100
                   ....*....|....*....|....*.
gi 157786960   440 LGSHEYIQHCRKFDINIRLQLMEQKA 465
Cdd:pfam00794   81 LGQFEYIRNCLKSGREPHLTLVEQSS 106
 
Name Accession Description Interval E-value
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 974-1327 0e+00

Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II beta isoform, PI3K-C2beta, contributes to the migration and survival of cancer cells. It regulates Rac activity and impacts membrane ruffling, cell motility, and cadherin-mediated cell-cell adhesion. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 119421 [Multi-domain]  Cd Length: 354  Bit Score: 737.97  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  974 REEFNRQCWLVNTLAKLAQQVREATPSARQGILRAGLEEVRQFFALNGSCRLPLSPSLLVKGIVPRDCSYFNSNAVPLKL 1053
Cdd:cd00895     1 REEFDRQCWLVNVLAKLAQQVREAAPSARQGILREGLEEVKQFFSINGSCRLPLSPSLLVKGIVPRDCSYFNSNAVPLKL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1054 AFQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGKGMVEMIPNAETLRKIQVEHG 1133
Cdd:cd00895    81 SFQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMNKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEHG 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1134 VTGSFKDRPLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYILGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGN 1213
Cdd:cd00895   161 VTGSFKDRPLADWLQKHNPTEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGN 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1214 IKRDRAPFVFTSDMAYVINGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQ 1293
Cdd:cd00895   241 IKRDRAPFVFTSDMAYVINGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQ 320

                         330       340       350
                  ....*....|....*....|....*....|....
gi 157786960 1294 DTEANATTYFTRLIESSLGSVATKLNFFIHNLAQ 1327
Cdd:cd00895   321 DTEADATTYFTRLIESSLGSVATKLNFFIHNLAQ 354
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
 800-968 2.39e-91

Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, class II PI3-kinases phosphorylate phosphoinositol (PtdIns), PtdIns(4)-phosphate, but not PtdIns(4,5)-bisphosphate. They are larger, having a C2 domain at the C-terminus.


Pssm-ID: 238441  Cd Length: 169  Bit Score: 293.21  E-value: 2.39e-91
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  800 EEDQRKLKDITQKESLYWLSDADKKQLWEKRYYCHTEVSSLPLVLASAPSWEWACLPDIYALLQQWTHMNHQDALGLLHA 879
Cdd:cd00869     1 IETQEKLLDLIQKQSTYTLSTEDKDLLWEKRLYCTNEPNALPLVLASAPSWDWANLMDVYQLLHQWAPLRPLIALELLLP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  880 TFPDQEVRRMAVQWIGSLSDAELLDYLPQLVQALKYECYLDSPLVRFLLKRAISDLRVTHYFFWLLKDSLKDSQFSIRYQ 959
Cdd:cd00869    81 KFPDQEVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALDDCYFSSAYQ 160


                  ....*....
gi 157786960  960 YLLAALLCC 968
Cdd:cd00869   161 DLGAALRCQ 169
PX_PI3K_C2_beta cd07290
The phosphoinositide binding Phox Homology Domain of the Beta Isoform of Class II ...
 1356-1464 1.70e-74

The phosphoinositide binding Phox Homology Domain of the Beta Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II beta isoform, PI3K-C2beta, contributes to the migration and survival of cancer cells. It regulates Rac activity and impacts membrane ruffling, cell motility, and cadherin-mediated cell-cell adhesion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


Pssm-ID: 132823  Cd Length: 109  Bit Score: 242.52  E-value: 1.70e-74
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1356 DVFLCRHEKVFHPSKGYIYVVKVMRENAHEATYIQRTFEEFQELHNKLRLLFPSSFLPSFPSRFVIGRSRGEAVAERRKE 1435
Cdd:cd07290     1 DVFLCRHESTFNPSKGYAYVVKVQREGHKEATFVQRTFEEFQELHNKLRLLFPSSKLPSFPSRFVIGRSRGEAVAERRKE 80

                          90       100
                  ....*....|....*....|....*....
gi 157786960 1436 ELNGYIWHLIHAAPEVAECDLVYTFFHPL 1464
Cdd:cd07290    81 ELNGYIWHLIHAPPEVAECDLVYTFFHPL 109
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 609-781 4.20e-74

C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. Class II PIK3s act downstream of receptors for growth factors, integrins, and chemokines. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. 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: 175979  Cd Length: 171  Bit Score: 243.80  E-value: 4.20e-74
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  609 QEACHFSGALAFTVYGTHRIPIIWATSYEEFYLSCSLSHGGKELCSPLQTRRAHFSKYLFHLIIWDQQICFPVQVNRLPR 688
Cdd:cd04012     1 REASTVTDLLSVTVSSLHRIPPTWVQSFEDFYLSCSLYHGGRLLCSPVTTKPVKITKSFFPRVVWDEWIEFPIPVCQLPR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  689 ETLLCATLYALPIPPPGSSseaNKQKRVPEALGWVTTPLFNFRQVLTCGRKLLGLWPATQENSSARWSAPNFHQPDSVIL 768
Cdd:cd04012    81 ESRLVLTLYGTTSSPDGGS---NKQRMGPEELGWVSLPLFDFRGVLRQGSLLLGLWPPSKDNPLGPAPPPLFEQPDRVIL 157

                         170
                  ....*....|...
gi 157786960  769 QIDFPTSAFDIKF 781
Cdd:cd04012   158 QIDFPSSAFDVIF 170
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 1067-1278 1.31e-73

Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in a variety of processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, and apoptosis. These homologues may be either lipid kinases and/or protein kinases: the former phosphorylate the 3-position in the inositol ring of inositol phospholipids. The ataxia telangiectesia-mutated gene produced, the targets of rapamycin (TOR) and the DNA-dependent kinase have not been found to possess lipid kinase activity. Some of this family possess PI-4 kinase activities.


Pssm-ID: 214538 [Multi-domain]  Cd Length: 240  Bit Score: 245.29  E-value: 1.31e-73
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960   1067 VIFKCGDDLRQDMLTLQMIRIMSKIWVQE----GLDMRMVIFRCFSTGRGKGMVEMIPNAETLRKIQVEH---------- 1132
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960   1133 ---------------GVTGSFKDRPLADWLQKHNPGEDE-YEKAVENFIYSCAGCCVATYILGICDRHNDNIMLKTTGHM 1196
Cdd:smart00146   81 rsqtatrlkklelflEATGKFPDPVLYDWFTKKFPDPSEdYFEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960   1197 FHIDFGRFLGHAQMFGNIKrDRAPFVFTSDMAYVINggdkPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPE 1276
Cdd:smart00146  161 FHIDFGFILGNGPKLFGFP-ERVPFRLTPEMVDVMG----DSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLPD 235


                    ..
gi 157786960   1277 LS 1278
Cdd:smart00146  236 WR 237
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 797-978 1.05e-71

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation.


Pssm-ID: 214537  Cd Length: 184  Bit Score: 237.54  E-value: 1.05e-71
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960    797 SLREEDQRKLKDITQKESLYWLSDADKKQLWEKRYYCHTEVS-SLPLVLaSAPSWEWAC-LPDIYALLQQWTHMNHQDAL 874
Cdd:smart00145    2 PLDIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPkALPKFL-LSVKWSDADeVAQALSLLLSWAPLDPEDAL 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960    875 GLLHATFPDQEVRRMAVQWIGSLSDAELLDYLPQLVQALKYECYLDSPLVRFLLKRAISDLRVTHYFFWLLKDSLKDSQF 954
Cdd:smart00145   81 ELLDPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHV 160

                           170       180
                    ....*....|....*....|....
gi 157786960    955 SIRYQYLLAALLCCCGKGLREEFN 978
Cdd:smart00145  161 SIRFGLLLEAYLRGCGTHLKELLK 184
C2B_PI3K_class_II cd08381
C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are ...
 1492-1614 2.35e-71

C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. 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: 176027 [Multi-domain]  Cd Length: 122  Bit Score: 234.11  E-value: 2.35e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1492 GGEVKLSISYKNNKLFIMVMHIRGLqPLQDGSDPDPYVKIYLLPDPQKATKRKTKVARKTCNPTYNEMLVYDGIPKGDLQ 1571
Cdd:cd08381     1 GGQVKLSISYKNGTLFVMVMHAKNL-PLLDGSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDGLPVEDLQ 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 157786960 1572 QRELQLSVLSEQGFWENVLLGEVHIRLRELDLAQEKTGWFALG 1614
Cdd:cd08381    80 QRVLQVSVWSHDSLVENEFLGGVCIPLKKLDLSQETEKWYPLG 122
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 1065-1260 2.71e-66

Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid kinase activity and are protein kinases,.


Pssm-ID: 395364 [Multi-domain]  Cd Length: 241  Bit Score: 224.52  E-value: 2.71e-66
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  1065 IRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDM-RMVIFRCFSTGRGKGMVEMIPNAETLRKIQVEHG-----VTGSF 1138
Cdd:pfam00454    2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEYGengvpPTAMV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  1139 KD-----------------------RPLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYILGICDRHNDNIML-KTTG 1194
Cdd:pfam00454   82 KIlhsalnypklklefesrislppkVGLLQWFVKKSPDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTTG 161

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 157786960  1195 HMFHIDFGRFLGHAQMFGNIKrDRAPFVFTSDMAYVINggdkPSSRFHDFVDLCCQAYNLIRKHTH 1260
Cdd:pfam00454  162 KLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAMG----PSGDEGLFRELCETAYEALRRNLN 222
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 799-977 3.23e-39

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation.


Pssm-ID: 395488  Cd Length: 185  Bit Score: 144.39  E-value: 3.23e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960   799 REEDQRKLKDITQKESLYWLSDADKKQLWEKRYYCHTEVSSLPLVLASApswEWACLPDI---YALLQQWTHMNHQDALG 875
Cdd:pfam00613    6 NEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYLMLVPKALTKLLLSV---KWSDLSEVaeaLSLLLKWAPIDPVDALE 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960   876 LLHATFPDQEVRRMAVQWIGSLSDAELLDYLPQLVQALKYECYLDSPLVRFLLKRAISDLRVTHYFFWLLKDSLKDSQFS 955
Cdd:pfam00613   83 LLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEIHDEEVS 162

                          170       180
                   ....*....|....*....|..
gi 157786960   956 IRYQYLLAALLCCCGKGLREEF 977
Cdd:pfam00613  163 PRFGSLLELYLRSCGTSLLGLN 184
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 635-775 1.43e-34

Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 domain. Outlier of pfam00168 family.


Pssm-ID: 395640  Cd Length: 136  Bit Score: 129.41  E-value: 1.43e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960   635 SYEEFYLSCSLSHGGKELCSPLQTRRAHFSKylfHLIIWDQQICFPVQVNRLPRETLLCATLYALPIPppgssseanKQK 714
Cdd:pfam00792    1 RQEDLYVECQLYHGGKPLCLPVSTRYVPFSN---SSIKWNEWITFPIQISDLPRSARLCITIWDVSGP---------EKS 68

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 157786960   715 RVPeaLGWVTTPLFNFRQVLTCGRKLLGLWPATQ-ENSSARW---------SAPNFHQPDSViLQIDFPTS 775
Cdd:pfam00792   69 FVP--IGWVNTSLFDKKGILRQGKQKLRLWPSKStPGRSNVDemnrlekllKKYERGQVSSV-DWLDFLTF 136
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 363-465 6.48e-32

PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding pfam00788 domains (unpublished observation).


Pssm-ID: 395642  Cd Length: 106  Bit Score: 120.48  E-value: 6.48e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960   363 TVTPSPEHL--GDEVNLKVTVLCDSLREPLTFTCNCSSTVDLLIYQTLCYTHDELREVDVG-DFVLKPCGLEEFLQNKHA 439
Cdd:pfam00794    1 ASTVSPEPLpkLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVTdDYVLKVCGRDEYLLGDHP 80

                           90       100
                   ....*....|....*....|....*.
gi 157786960   440 LGSHEYIQHCRKFDINIRLQLMEQKA 465
Cdd:pfam00794   81 LGQFEYIRNCLKSGREPHLTLVEQSS 106
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
1049-1328 8.88e-30

Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 129.90  E-value: 8.88e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1049 VPLKLAFQNVDplGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMR----MVIFRCFSTGRGKGMVEMIPNAET 1124
Cdd:COG5032  1783 RPRRLTIRGSD--GKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKETRRrdlwIRPYKVIPLSPGSGIIEWVPNSDT 1860

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1125 LRKI--------------------QVEHGVTG---------SFKDRP-LADWLQKHNPGEDEYEKAVENFIYSCAGCCVA 1174
Cdd:COG5032  1861 LHSIlreyhkrknisidqekklaaRLDNLKLLlkdefftkaTLKSPPvLYDWFSESFPNPEDWLTARTNFARSLAVYSVI 1940

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1175 TYILGICDRHNDNIML-KTTGHMFHIDFGRFLGhAQMFGNIKRDRAPFVFTSDMAYVING-GDKPSsrfhdFVDLCCQAY 1252
Cdd:COG5032  1941 GYILGLGDRHPGNILIdRSSGHVIHIDFGFILF-NAPGRFPFPEKVPFRLTRNIVEAMGVsGVEGS-----FRELCETAF 2014

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1253 NLIRKHTHL------FLNLLGLMLSCGIPELSD--LEDLKYVYDALRPQDTEANATTYFTRLIESSLGSVATKL-NFFih 1323
Cdd:COG5032  2015 RALRKNADSlmnvleLFVRDPLIEWRRLPCFREiqNNEIVNVLERFRLKLSEKDAEKFVDLLINKSVESLITQAtDPF-- 2092


                  ....*
gi 157786960 1324 NLAQM 1328
Cdd:COG5032  2093 QLATM 2097
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 608-709 4.14e-27

Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.


Pssm-ID: 214536  Cd Length: 100  Bit Score: 106.66  E-value: 4.14e-27
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960    608 VQEACHFSGALAFTVYGTHRIPIIWATSYEEFYLSCSLSHGGKELCSPLQTRRAHFSKYlfhlIIWDQQICFPVQVNRLP 687
Cdd:smart00142    3 IESLWDCDRNLVITIALIHGIPLNWSRDYSDLYVEIQLYHGGKLLCLPVSTSYKPFFPS----VKWNEWLTFPIQISDLP 78

                            90       100
                    ....*....|....*....|..
gi 157786960    688 RETLLCATLYALPIPPPGSSSE 709
Cdd:smart00142   79 REARLCITIYAVKNPSKGSEFG 100
PX smart00312
PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function ...
 1366-1462 9.91e-24

PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function present in phox proteins, PLD isoforms, a PI3K isoform.


Pssm-ID: 214610  Cd Length: 105  Bit Score: 97.41  E-value: 9.91e-24
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960   1366 FHPSKGYIYVVKVMRENAHEATYIQRTFEEFQELHNKLRLLFPSSFLPSFPSRFVIGRSR--GEAVAERRKEELNGYIWH 1443
Cdd:smart00312    7 IGDGKHYYYVIEIETKTGLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRLNnfSEEFIEKRRRGLEKYLQS 86

                            90
                    ....*....|....*....
gi 157786960   1444 LIHAAPEVAECDLVYTFFH 1462
Cdd:smart00312   87 LLNHPELINHSEVVLEFLE 105
C2 pfam00168
C2 domain;
1504-1613 1.23e-23

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 97.00  E-value: 1.23e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  1504 NKLFIMVMHIRGLQPLQDGSDPDPYVKIYLLpdpQKATKRKTKVARKTCNPTYNEMLVYDgIPkgDLQQRELQLSVLSEQ 1583
Cdd:pfam00168    1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLL---DGKQKKKTKVVKNTLNPVWNETFTFS-VP--DPENAVLEIEVYDYD 74

                           90       100       110
                   ....*....|....*....|....*....|
gi 157786960  1584 GFWENVLLGEVHIRLRELDLAQEKTGWFAL 1613
Cdd:pfam00168   75 RFGRDDFIGEVRIPLSELDSGEGLDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 1505-1610 3.92e-22

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 92.55  E-value: 3.92e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960   1505 KLFIMVMHIRGLQPLQDGSDPDPYVKIYLLPDPQKatKRKTKVARKTCNPTYNEMLVYDGIPkgdLQQRELQLSVLSEQG 1584
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKE--KKKTKVVKNTLNPVWNETFEFEVPP---PELAELEIEVYDKDR 75

                            90       100
                    ....*....|....*....|....*.
gi 157786960   1585 FWENVLLGEVHIRLRELDLAQEKTGW 1610
Cdd:smart00239   76 FGRDDFIGQVTIPLSDLLLGGRHEKL 101
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 363-463 1.43e-16

PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding RA domains (unpublished observation).


Pssm-ID: 197540  Cd Length: 108  Bit Score: 76.98  E-value: 1.43e-16
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960    363 TVTPSPEHLGDEV---NLKVTVLCDSLREPLTFTCNCSSTVDLLIYQTLCYTHDELREVDVG--DFVLKPCGLEEFLQNK 437
Cdd:smart00144    1 TSPSVPEPLPLKTianKILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQVDPTseDYILKVCGRDEYLLGD 80

                            90       100
                    ....*....|....*....|....*.
gi 157786960    438 HALGSHEYIQHCRKFDINIRLQLMEQ 463
Cdd:smart00144   81 HPLGSFEYIRNCLKNGTEPHLVLMTL 106
PX pfam00787
PX domain; PX domains bind to phosphoinositides.
 1389-1463 3.16e-16

PX domain; PX domains bind to phosphoinositides.


Pssm-ID: 459940  Cd Length: 84  Bit Score: 74.97  E-value: 3.16e-16
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 157786960  1389 IQRTFEEFQELHNKLRLLFPSSFLPSFPSRFVIGRSRgEAVAERRKEELNGYIWHLIHaAPEVAECDLVYTFFHP 1463
Cdd:pfam00787   11 VRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLGRYN-EEFIEKRRKGLEQYLQRLLQ-HPELRNSEVLLEFLES 83
 
Name Accession Description Interval E-value
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 974-1327 0e+00

Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II beta isoform, PI3K-C2beta, contributes to the migration and survival of cancer cells. It regulates Rac activity and impacts membrane ruffling, cell motility, and cadherin-mediated cell-cell adhesion. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 119421 [Multi-domain]  Cd Length: 354  Bit Score: 737.97  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  974 REEFNRQCWLVNTLAKLAQQVREATPSARQGILRAGLEEVRQFFALNGSCRLPLSPSLLVKGIVPRDCSYFNSNAVPLKL 1053
Cdd:cd00895     1 REEFDRQCWLVNVLAKLAQQVREAAPSARQGILREGLEEVKQFFSINGSCRLPLSPSLLVKGIVPRDCSYFNSNAVPLKL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1054 AFQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGKGMVEMIPNAETLRKIQVEHG 1133
Cdd:cd00895    81 SFQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMNKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEHG 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1134 VTGSFKDRPLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYILGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGN 1213
Cdd:cd00895   161 VTGSFKDRPLADWLQKHNPTEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGN 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1214 IKRDRAPFVFTSDMAYVINGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQ 1293
Cdd:cd00895   241 IKRDRAPFVFTSDMAYVINGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQ 320

                         330       340       350
                  ....*....|....*....|....*....|....
gi 157786960 1294 DTEANATTYFTRLIESSLGSVATKLNFFIHNLAQ 1327
Cdd:cd00895   321 DTEADATTYFTRLIESSLGSVATKLNFFIHNLAQ 354
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 974-1327 0e+00

Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. They are activated by a variety of stimuli including chemokines, cytokines, lysophosphatidic acid (LPA), insulin, and tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270710 [Multi-domain]  Cd Length: 352  Bit Score: 677.47  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  974 REEFNRQCWLVNTLAKLAQQVREATPSARQGILRAGLEEVRQFFALNgSCRLPLSPSLLVKGIVPRDCSYFNSNAVPLKL 1053
Cdd:cd05166     1 REEFLKQHVLVQALTSIAEKVKSAKDSARENALRRELEQLASFLLEN-SFRLPLDPALEVTGVDVRSCSYFNSNALPLKL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1054 AFQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGKGMVEMIPNAETLRKIQVEHG 1133
Cdd:cd05166    80 VFRNADPRAEPISVIFKVGDDLRQDMLTLQLIRIMDKIWLQEGLDLKMITFRCVPTGNKRGMVELVPEAETLREIQTEHG 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1134 VTGSFKDRPLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYILGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGN 1213
Cdd:cd05166   160 LTGSFKDRPLADWLQKHNPSELEYEKAVENFIRSCAGYCVATYVLGICDRHNDNIMLKTSGHLFHIDFGKFLGDAQMFGN 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1214 IKRDRAPFVFTSDMAYVINGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSdLEDLKYVYDALRPQ 1293
Cdd:cd05166   240 FKRDRVPFVLTSDMAYVINGGDKPSSRFQLFVDLCCQAFNIIRKNSNLLLNLLSLMLSSGIPGVT-QDDLRYVQDALLPE 318

                         330       340       350
                  ....*....|....*....|....*....|....
gi 157786960 1294 DTEANATTYFTRLIESSLGSVATKLNFFIHNLAQ 1327
Cdd:cd05166   319 LTDAEATAHFTRMIEESLSSKFTQLNFFIHNLAQ 352
PI3Kc_C2_alpha cd05176
Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 974-1327 0e+00

Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II alpha isoform, PI3K-C2alpha, plays key roles in clathrin assembly and clathrin-mediated membrane trafficking, insulin signaling, vascular smooth muscle contraction, and the priming of neurosecretory granule exocytosis. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270720 [Multi-domain]  Cd Length: 353  Bit Score: 591.18  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  974 REEFNRQCWLVNTLAKLAQQVREATPSARQGILRAGLEEVRQFFALNgSCRLPLSPSLLVKGIVPRDCSYFNSNAVPLKL 1053
Cdd:cd05176     1 REELEKQTRLVQLLGRVAEKVRQASGSARQVALQDGMERVQSFFQKN-KCRLPLSPSLVAKELNIKACSFFSSNAVPLKV 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1054 AFQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGKGMVEMIPNAETLRKIQVEHG 1133
Cdd:cd05176    80 ALVNADPLGEEINVMFKVGEDLRQDMLALQMIKIMDKIWLQEGLDLRMVIFKCLSTGKDRGMVELVPSSDTLRKIQVEYG 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1134 VTGSFKDRPLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYILGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGN 1213
Cdd:cd05176   160 VTGSFKDKPLAEWLRKYNPSEEEYEKASENFIYSCAGCCVATYVLGICDRHNDNIMLRSTGHMFHIDFGKFLGHAQMFGS 239

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1214 IKRDRAPFVFTSDMAYVINGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQ 1293
Cdd:cd05176   240 FKRDRAPFVLTSDMAYVINGGEKPTIRFQLFVDLCCQAYNLIRKHTNLFLNLLSLMLSSGLPELTGIQDLKYVFDALQPQ 319

                         330       340       350
                  ....*....|....*....|....*....|....
gi 157786960 1294 DTEANATTYFTRLIESSLGSVATKLNFFIHNLAQ 1327
Cdd:cd05176   320 TTDAEATIFFTRLIESSLGSVATKFNFFIHNLAQ 353
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 974-1312 6.81e-159

Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. Class II PI3Ks comprise three catalytic isoforms that do not associate with any regulatory subunits. They selectively use PtdIns as a susbtrate to produce PtsIns(3)P. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270624 [Multi-domain]  Cd Length: 334  Bit Score: 485.54  E-value: 6.81e-159
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  974 REEFNRQCWLVNTLAKLAQQVREATPSARQGILRAGLEEVRQFFalngSCRLPLSPSLLVKGIVPRDCSYFNSNAVPLKL 1053
Cdd:cd00891     1 REELLKQVKVLDELKEIAKKIKEEPSEERKEVLEKLLQKLELPK----KFTLPLDPRMEVKGLIVEKCKVMDSKKLPLWL 76

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1054 AFQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGKGMVEMIPNAETLRKIQVE-H 1132
Cdd:cd00891    77 VFKNADPGGDPIKVIFKAGDDLRQDQLTLQLLRIMDKLWKKEGLDLRMTPYKCIATGDEVGMIEVVPNSETTAAIQKKyG 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1133 GVTGSFKDRPLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYILGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFG 1212
Cdd:cd00891   157 GFGAAFKDTPISNWLKKHNPTEEEYEEAVENFIRSCAGYCVATYVLGIGDRHNDNIMVTKSGHLFHIDFGHFLGNFKKKF 236

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1213 NIKRDRAPFVFTSDMAYVINGGDkpSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRP 1292
Cdd:cd00891   237 GIKRERAPFVFTPEMAYVMGGED--SENFQKFEDLCCKAYNILRKHGNLLINLFSLMLSAGIPELQSIEDIEYLRDALQL 314

                         330       340
                  ....*....|....*....|
gi 157786960 1293 QDTEANATTYFTRLIESSLG 1312
Cdd:cd00891   315 DLSDEEAAEHFRKLIHESLN 334
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 974-1327 4.32e-156

Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II gamma isoform, PI3K-C2gamma, is expressed in the liver, breast, and prostate. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. It's biological function remains unknown. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270721 [Multi-domain]  Cd Length: 354  Bit Score: 479.00  E-value: 4.32e-156
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  974 REEFNRQCWLVNTLAKLAQQVREATPSARQGILRAGLEEVRQFFALNGSCRLPLSPSLLVKGIVPRDCSYFNSNAVPLKL 1053
Cdd:cd05177     1 NKEFSKETKLISILIDAAEKVKTASDTRRKEVLKREASRLEDFFQDVVSCCLPLNPALRVKGIDADACSYFTSNAAPLKI 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1054 AFQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGKGMVEMIPNAETLRKIQVEHG 1133
Cdd:cd05177    81 SFINANPLAKNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYRCLSTGKTQGLVQMVPDAVTLAKIHRESG 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1134 VTGSFKDRPLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYILGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGN 1213
Cdd:cd05177   161 LIGPLKENTIEKWFHMHNKLKEDYDKAVRNFFHSCAGWCVVTFILGVCDRHNDNIMLTHSGHMFHIDFGKFLGHAQTFGS 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1214 IKRDRAPFVFTSDMAYVINGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQ 1293
Cdd:cd05177   241 IKRDRAPFIFTSEMEYFITEGGKKPQRFQRFVELCCRAYNIVRKHSQLLLNLLEMMLHAGLPELKDIQDLKYVYNNLRPQ 320

                         330       340       350
                  ....*....|....*....|....*....|....
gi 157786960 1294 DTEANATTYFTRLIESSLGSVATKLNFFIHNLAQ 1327
Cdd:cd05177   321 DTDLEATSYFTKKIKESLECFPVKLNNLIHTLAQ 354
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 977-1327 1.28e-121

Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. In vitro, they can also phosphorylate the substrates PtdIns and PtdIns(4)P. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270709 [Multi-domain]  Cd Length: 363  Bit Score: 385.83  E-value: 1.28e-121
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  977 FNRQCWLVNTLAKLAQQVREATPSARQGILRagLEEVRQFFALNGSCR---LPLSPSLLVKGIVPRDCSYFNSNAVPLKL 1053
Cdd:cd05165     4 LSRQVEALNKLKKLSDILKEKKKSKEKVKKL--LKECLKQKFYDEALQnfqSPLNPSHKLGELIIEKCKVMDSKKRPLWL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1054 AFQNVDPL---GENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGKGMVEMIPNAETLRKIQV 1130
Cdd:cd05165    82 VFENADPLalsGEDIKIIFKNGDDLRQDMLTLQIIRIMDNIWKEEGLDLRMLPYGCLSTGDNVGLIEVVRNAKTIANIQK 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1131 EHG--VTGSFKDRPLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYILGICDRHNDNIMLKTTGHMFHIDFGRFLGHA 1208
Cdd:cd05165   162 KKGkvATLAFNKDSLHKWLKEKNKTGEKYDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVKENGQLFHIDFGHFLGNF 241

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1209 QMFGNIKRDRAPFVFTSDMAYVI-NGGDKPSS-RFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYV 1286
Cdd:cd05165   242 KKKFGIKRERVPFVLTHDFVYVIaRGQDNTKSeEFQEFQELCEKAYLILRRHGNLFISLFSMMLSTGIPELTSVKDIEYL 321

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|..
gi 157786960 1287 YDALRPQDTEANATTYFTRLIESSL-GSVATKLNFFIHNLAQ 1327
Cdd:cd05165   322 RKTLALDKTEEEALKYFRKKFNEALkGSWTTKVNWFFHNVKH 363
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
 800-968 2.39e-91

Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, class II PI3-kinases phosphorylate phosphoinositol (PtdIns), PtdIns(4)-phosphate, but not PtdIns(4,5)-bisphosphate. They are larger, having a C2 domain at the C-terminus.


Pssm-ID: 238441  Cd Length: 169  Bit Score: 293.21  E-value: 2.39e-91
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  800 EEDQRKLKDITQKESLYWLSDADKKQLWEKRYYCHTEVSSLPLVLASAPSWEWACLPDIYALLQQWTHMNHQDALGLLHA 879
Cdd:cd00869     1 IETQEKLLDLIQKQSTYTLSTEDKDLLWEKRLYCTNEPNALPLVLASAPSWDWANLMDVYQLLHQWAPLRPLIALELLLP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  880 TFPDQEVRRMAVQWIGSLSDAELLDYLPQLVQALKYECYLDSPLVRFLLKRAISDLRVTHYFFWLLKDSLKDSQFSIRYQ 959
Cdd:cd00869    81 KFPDQEVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALDDCYFSSAYQ 160


                  ....*....
gi 157786960  960 YLLAALLCC 968
Cdd:cd00869   161 DLGAALRCQ 169
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 975-1329 5.95e-86

Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kgamma signaling controls diverse immune and vascular functions including cell recruitment, mast cell activation, platelet aggregation, and smooth muscle contractility. It associates with one of two regulatory subunits, p101 and p84, and is activated by G-protein-coupled receptors (GPCRs) by direct binding to their betagamma subunits. It contains an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270627 [Multi-domain]  Cd Length: 367  Bit Score: 285.99  E-value: 5.95e-86
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  975 EEFNRQCWLVNTLAKLAQQVR----EATPSARQGI--LRAGLEEVrQFFALNGSCRLPLSPSLLVKGIVPRDCSYFNSNA 1048
Cdd:cd00894     2 HDFTQQVQVIEMLQKVTLDIKslsaEKYDVSSQVIsqLKQKLENL-QNSQLPESFRVPYDPGLRAGALVIEKCKVMASKK 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1049 VPLKLAFQNVDPLG---ENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGKGMVEMIPNAETL 1125
Cdd:cd00894    81 KPLWLEFKCADPTAlsnETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTI 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1126 RKIQVEH-GVTGSFKDRPLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYILGICDRHNDNIMLKTTGHMFHIDFGRF 1204
Cdd:cd00894   161 AKIQQSTvGNTGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHI 240

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1205 LGHAQMFGNIKRDRAPFVFTSDMAYVI-NGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDL 1283
Cdd:cd00894   241 LGNYKSFLGINKERVPFVLTPDFLFVMgTSGKKTSLHFQKFQDVCVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 320

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*..
gi 157786960 1284 KYVYDALRPQDTEANATTYFTRLIESSLGSVAT-KLNFFIHNLAQMK 1329
Cdd:cd00894   321 EYIRDALTVGKSEEDAKKHFLDQIEVCRDKGWTvQFNWFLHLVLGIK 367
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 974-1327 7.63e-81

Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. Class III PI3Ks, also called Vps34 (vacuolar protein sorting 34), contain an N-terminal lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They phosphorylate only the substrate PtdIns. They interact with a regulatory subunit, Vps15, to form a membrane-associated complex. Class III PI3Ks are involved in protein and vesicular trafficking and sorting, autophagy, trimeric G-protein signaling, and phagocytosis. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270628 [Multi-domain]  Cd Length: 346  Bit Score: 270.56  E-value: 7.63e-81
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  974 REEFNRQCWLVNTLAKLAQQVREATPSARQGI--LRAGLEE-VRQFFALNGSCRLPLSPSLLVKGIVPRDCSYFNSNAVP 1050
Cdd:cd00896     1 REALKRQQEFVDRLRSLMKEVKNEKGSRDKKIerLRELLSDsELGLLLFFEPLPLPLDPSVKVTGIIPEKSTVFKSALMP 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1051 LKLAFQNVDplGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGKGMVEMIPNAETLRKIQV 1130
Cdd:cd00896    81 LKLTFKTLD--GGEYKVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVPNSKALADILK 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1131 EHGvtgsfkdrPLADWLQKHNPGED----EYEKAVENFIYSCAGCCVATYILGICDRHNDNIMLKTTGHMFHIDFGRFLG 1206
Cdd:cd00896   159 KYG--------SILNFLRKHNPDESgpygIKPEVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHIDFGYILG 230

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1207 haqmfgnikRDRAPFV----FTSDMayvING-GDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLE 1281
Cdd:cd00896   231 ---------RDPKPFPppmkLCKEM---VEAmGGANSEGYKEFKKYCCTAYNILRKHANLILNLFSLMVDANIPDIALEP 298

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*...
gi 157786960 1282 D--LKYVYDALRPQDTEANATTYFTRLIESSLGSVATKLNFFIHNLAQ 1327
Cdd:cd00896   299 DkaVLKVQEKFRLDLSDEEAEQYFQNLIDESVNALFPAVVETIHKIAQ 346
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 1026-1327 8.13e-81

Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kdelta is mainly expressed in immune cells and plays an important role in cellular and humoral immunity. It plays a major role in antigen receptor signaling in B-cells, T-cells, and mast cells. It regulates the differentiation of peripheral helper T-cells and controls the development and function of regulatory T-cells. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270718 [Multi-domain]  Cd Length: 366  Bit Score: 271.15  E-value: 8.13e-81
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1026 PLSPSLLVKGIVPRDCSYFNSNAVPLKLAFQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFR 1105
Cdd:cd05174    59 PLDPSIILEEVCVDQCTFMDSKMKPLWIMYSSEEAGAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYG 138

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1106 CFSTGRGKGMVEMIPNAETLRKIQVEH---GVTGSFKDRPLADWLQKHNPGeDEYEKAVENFIYSCAGCCVATYILGICD 1182
Cdd:cd05174   139 CLSTGDKTGLIEVVLHSDTIANIQLNKsnmAATAAFNKDALLNWLKSKNPG-DALDQAIEEFTLSCAGYCVATYVLGIGD 217

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1183 RHNDNIMLKTTGHMFHIDFGRFLGHAQMFGNIKRDRAPFVFTSDMAYVINGGDKPSS-RFHDFVDLCCQAYNLIRKHTHL 1261
Cdd:cd05174   218 RHSDNIMIRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSeKFERFRGYCERAYTILRRHGLL 297

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 157786960 1262 FLNLLGLMLSCGIPELSDLEDLKYVYDALRPQDTEANATTYF-TRLIESSLGSVATKLNFFIHNLAQ 1327
Cdd:cd05174   298 FLHLFALMKAAGLPELSCSKDIQYLKDSLALGKTEEEALKHFrVKFNEALRESWKTKVNWLAHNVSK 364
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 1026-1327 1.72e-76

Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kbeta can be activated by G-protein-coupled receptors. Deletion of PI3Kbeta in mice results in early lethality at around day three of development. PI3Kbeta plays an important role in regulating sustained integrin activation and stable platelet agrregation, especially under conditions of high shear stress. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270717 [Multi-domain]  Cd Length: 362  Bit Score: 258.74  E-value: 1.72e-76
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1026 PLSPSLLVKGIVPRDCSYFNSNAVPLKLAFQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFR 1105
Cdd:cd05173    56 PLNPSIILSELNVEKCKYMDSKMKPLWIVYNNKLFGGDSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVPYG 135

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1106 CFSTGRGKGMVEMIPNAETLRKIQVEH---GVTGSFKDRPLADWLQKHNPGeDEYEKAVENFIYSCAGCCVATYILGICD 1182
Cdd:cd05173   136 CLATGDRSGLIEVVSSAETIADIQLNSsnvAAAAAFNKDALLNWLKEYNSG-DDLERAIEEFTLSCAGYCVATYVLGIGD 214

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1183 RHNDNIMLKTTGHMFHIDFGRFLGHAQMFGNIKRDRAPFVFTSDMAYVINGGdKP--SSRFHDFVDLCCQAYNLIRKHTH 1260
Cdd:cd05173   215 RHSDNIMVRKNGQLFHIDFGHILGNFKSKFGIKRERVPFILTYDFIHVIQQG-KTgnTEKFGRFRQYCEDAYLILRKNGN 293

                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 157786960 1261 LFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQDTEANATTYFTRLIESSLG-SVATKLNFFIHNLAQ 1327
Cdd:cd05173   294 LFITLFALMLTAGLPELTSVKDIQYLKDSLALGKSEEEALKQFRQKFDEALReSWTTKVNWMAHTVRK 361
PX_PI3K_C2_beta cd07290
The phosphoinositide binding Phox Homology Domain of the Beta Isoform of Class II ...
 1356-1464 1.70e-74

The phosphoinositide binding Phox Homology Domain of the Beta Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II beta isoform, PI3K-C2beta, contributes to the migration and survival of cancer cells. It regulates Rac activity and impacts membrane ruffling, cell motility, and cadherin-mediated cell-cell adhesion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


Pssm-ID: 132823  Cd Length: 109  Bit Score: 242.52  E-value: 1.70e-74
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1356 DVFLCRHEKVFHPSKGYIYVVKVMRENAHEATYIQRTFEEFQELHNKLRLLFPSSFLPSFPSRFVIGRSRGEAVAERRKE 1435
Cdd:cd07290     1 DVFLCRHESTFNPSKGYAYVVKVQREGHKEATFVQRTFEEFQELHNKLRLLFPSSKLPSFPSRFVIGRSRGEAVAERRKE 80

                          90       100
                  ....*....|....*....|....*....
gi 157786960 1436 ELNGYIWHLIHAAPEVAECDLVYTFFHPL 1464
Cdd:cd07290    81 ELNGYIWHLIHAPPEVAECDLVYTFFHPL 109
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 609-781 4.20e-74

C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. Class II PIK3s act downstream of receptors for growth factors, integrins, and chemokines. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. 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: 175979  Cd Length: 171  Bit Score: 243.80  E-value: 4.20e-74
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  609 QEACHFSGALAFTVYGTHRIPIIWATSYEEFYLSCSLSHGGKELCSPLQTRRAHFSKYLFHLIIWDQQICFPVQVNRLPR 688
Cdd:cd04012     1 REASTVTDLLSVTVSSLHRIPPTWVQSFEDFYLSCSLYHGGRLLCSPVTTKPVKITKSFFPRVVWDEWIEFPIPVCQLPR 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  689 ETLLCATLYALPIPPPGSSseaNKQKRVPEALGWVTTPLFNFRQVLTCGRKLLGLWPATQENSSARWSAPNFHQPDSVIL 768
Cdd:cd04012    81 ESRLVLTLYGTTSSPDGGS---NKQRMGPEELGWVSLPLFDFRGVLRQGSLLLGLWPPSKDNPLGPAPPPLFEQPDRVIL 157

                         170
                  ....*....|...
gi 157786960  769 QIDFPTSAFDIKF 781
Cdd:cd04012   158 QIDFPSSAFDVIF 170
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 1067-1278 1.31e-73

Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in a variety of processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, and apoptosis. These homologues may be either lipid kinases and/or protein kinases: the former phosphorylate the 3-position in the inositol ring of inositol phospholipids. The ataxia telangiectesia-mutated gene produced, the targets of rapamycin (TOR) and the DNA-dependent kinase have not been found to possess lipid kinase activity. Some of this family possess PI-4 kinase activities.


Pssm-ID: 214538 [Multi-domain]  Cd Length: 240  Bit Score: 245.29  E-value: 1.31e-73
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960   1067 VIFKCGDDLRQDMLTLQMIRIMSKIWVQE----GLDMRMVIFRCFSTGRGKGMVEMIPNAETLRKIQVEH---------- 1132
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960   1133 ---------------GVTGSFKDRPLADWLQKHNPGEDE-YEKAVENFIYSCAGCCVATYILGICDRHNDNIMLKTTGHM 1196
Cdd:smart00146   81 rsqtatrlkklelflEATGKFPDPVLYDWFTKKFPDPSEdYFEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960   1197 FHIDFGRFLGHAQMFGNIKrDRAPFVFTSDMAYVINggdkPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPE 1276
Cdd:smart00146  161 FHIDFGFILGNGPKLFGFP-ERVPFRLTPEMVDVMG----DSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLPD 235


                    ..
gi 157786960   1277 LS 1278
Cdd:smart00146  236 WR 237
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 797-978 1.05e-71

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation.


Pssm-ID: 214537  Cd Length: 184  Bit Score: 237.54  E-value: 1.05e-71
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960    797 SLREEDQRKLKDITQKESLYWLSDADKKQLWEKRYYCHTEVS-SLPLVLaSAPSWEWAC-LPDIYALLQQWTHMNHQDAL 874
Cdd:smart00145    2 PLDIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPkALPKFL-LSVKWSDADeVAQALSLLLSWAPLDPEDAL 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960    875 GLLHATFPDQEVRRMAVQWIGSLSDAELLDYLPQLVQALKYECYLDSPLVRFLLKRAISDLRVTHYFFWLLKDSLKDSQF 954
Cdd:smart00145   81 ELLDPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHV 160

                           170       180
                    ....*....|....*....|....
gi 157786960    955 SIRYQYLLAALLCCCGKGLREEFN 978
Cdd:smart00145  161 SIRFGLLLEAYLRGCGTHLKELLK 184
C2B_PI3K_class_II cd08381
C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are ...
 1492-1614 2.35e-71

C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. 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: 176027 [Multi-domain]  Cd Length: 122  Bit Score: 234.11  E-value: 2.35e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1492 GGEVKLSISYKNNKLFIMVMHIRGLqPLQDGSDPDPYVKIYLLPDPQKATKRKTKVARKTCNPTYNEMLVYDGIPKGDLQ 1571
Cdd:cd08381     1 GGQVKLSISYKNGTLFVMVMHAKNL-PLLDGSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDGLPVEDLQ 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 157786960 1572 QRELQLSVLSEQGFWENVLLGEVHIRLRELDLAQEKTGWFALG 1614
Cdd:cd08381    80 QRVLQVSVWSHDSLVENEFLGGVCIPLKKLDLSQETEKWYPLG 122
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 969-1327 2.34e-68

Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kalpha plays an important role in insulin signaling. It also mediates physiologic heart growth and provides protection from stress. Activating mutations of PI3Kalpha is associated with diverse forms of cancer at high frequency. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270719 [Multi-domain]  Cd Length: 370  Bit Score: 235.34  E-value: 2.34e-68
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  969 CGKGLREeFNRQCW----LVNTLAKLAQQVREATPSARQGILRAGLEEVRQFFALNGSCRlPLSPSLLVKGIVPRDCSYF 1044
Cdd:cd05175     1 CGMYLKH-LSRQVEamekLINLTDILKQEKKDETQKVQMKFLVEQMRRPDFMDALQGFLS-PLNPAHQLGNLRLEECRIM 78

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1045 NSNAVPLKLAFQNVDPLGE----NIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGKGMVEMIP 1120
Cdd:cd05175    79 SSAKRPLWLNWENPDIMSEllfqNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVR 158

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1121 NAETLRKIQVEHGVTGS--FKDRPLADWLQKHNPGEDeYEKAVENFIYSCAGCCVATYILGICDRHNDNIMLKTTGHMFH 1198
Cdd:cd05175   159 NSHTIMQIQCKGGLKGAlqFNSHTLHQWLKDKNKGEI-YDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFH 237

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1199 IDFGRFLGHAQMFGNIKRDRAPFVFTSDMAYVINGGDKPSSR---FHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIP 1275
Cdd:cd05175   238 IDFGHFLDHKKKKFGYKRERVPFVLTQDFLIVISKGAQECTKtreFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMP 317

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|...
gi 157786960 1276 ELSDLEDLKYVYDALRPQDTEANATTYFTRLI-ESSLGSVATKLNFFIHNLAQ 1327
Cdd:cd05175   318 ELQSFDDIAYIRKTLALDKTEQEALEYFMKQMnDAHHGGWTTKMDWIFHTIKQ 370
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 1065-1260 2.71e-66

Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid kinase activity and are protein kinases,.


Pssm-ID: 395364 [Multi-domain]  Cd Length: 241  Bit Score: 224.52  E-value: 2.71e-66
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  1065 IRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDM-RMVIFRCFSTGRGKGMVEMIPNAETLRKIQVEHG-----VTGSF 1138
Cdd:pfam00454    2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEYGengvpPTAMV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  1139 KD-----------------------RPLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYILGICDRHNDNIML-KTTG 1194
Cdd:pfam00454   82 KIlhsalnypklklefesrislppkVGLLQWFVKKSPDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTTG 161

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 157786960  1195 HMFHIDFGRFLGHAQMFGNIKrDRAPFVFTSDMAYVINggdkPSSRFHDFVDLCCQAYNLIRKHTH 1260
Cdd:pfam00454  162 KLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAMG----PSGDEGLFRELCETAYEALRRNLN 222
PI3Ka cd00864
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 801-951 1.38e-59

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in PI3 and PI4-kinases. Its role is unclear, but it has been suggested to be involved in substrate presentation. Phosphoinositide 3-kinases play an important role in a variety of fundamental cellular processes and can be divided into three main classes, defined by their substrate specificity and domain architecture.


Pssm-ID: 238440  Cd Length: 152  Bit Score: 201.67  E-value: 1.38e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  801 EDQRKLKDITQKESLYWLSDADKKQLWEKRYYCHTEVSSLPLVLASAPSWEWACLPDIYALLQQWTHMNHQDALGLLHAT 880
Cdd:cd00864     2 WERKPLLAILLYPPFSTLTEEEKELLWKFRYYLLNVPKALPKLLKSVNWNDDEEVSELYQLLKWWAPLSPEDALELLSPK 81

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 157786960  881 FPDQEVRRMAVQWIGSLSDAELLDYLPQLVQALKYECYLDSPLVRFLLKRAISDLRVTHYFFWLLKDSLKD 951
Cdd:cd00864    82 YPDPVVRQYAVRVLESASDDELLLYLPQLVQALKYEPYLDSYLARFLLERALKSQRLGHQLYWNLKSEIHD 152
PX_PI3K_C2 cd06883
The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases; The ...
 1356-1464 2.75e-55

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They are also involved in the regulation of clathrin-mediated membrane trafficking as well as ATP-dependent priming of neurosecretory granule exocytosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. Class II PI3Ks include three vertebrate isoforms (alpha, beta, and gamma), the Drosophila PI3K_68D, and similar proteins.


Pssm-ID: 132793  Cd Length: 109  Bit Score: 187.56  E-value: 2.75e-55
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1356 DVFLCRHEKVFHPSKGYIYVVKVMRENAHEATYIQRTFEEFQELHNKLRLLFPSSFLPSFPSRFVIGRSRGEAVAERRKE 1435
Cdd:cd06883     1 EVSVFGFQKRYSPEKYYIYVVKVTRENQTEPSFVFRTFEEFQELHNKLSLLFPSLKLPSFPARVVLGRSHIKQVAERRKI 80

                          90       100
                  ....*....|....*....|....*....
gi 157786960 1436 ELNGYIWHLIHAAPEVAECDLVYTFFHPL 1464
Cdd:cd06883    81 ELNSYLKSLFNASPEVAESDLVYTFFHPL 109
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
 1067-1318 2.02e-52

Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 4-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) to generate PtdIns(4)P, the major precursor in the synthesis of other phosphoinositides including PtdIns(4,5)P2, PtdIns(3,4)P2, and PtdIns(3,4,5)P3. Two isoforms of type III PI4K, alpha and beta, exist in most eukaryotes. PI4KIIIalpha is a 220 kDa protein found in the plasma membrane and the endoplasmic reticulum (ER). The role of PI4KIIIalpha in the ER remains unclear. In the plasma membrane, it provides PtdIns(4)P, which is then converted by PI5Ks to PtdIns(4,5)P2, an important signaling molecule. Vertebrate PI4KIIIalpha is also part of a signaling complex associated with P2X7 ion channels. The yeast homolog, Stt4p, is also important in regulating the conversion of phosphatidylserine to phosphatidylethanolamine at the ER and Golgi interface. Mammalian PI4KIIIalpha is highly expressed in the nervous system. The PI4K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270711 [Multi-domain]  Cd Length: 307  Bit Score: 187.03  E-value: 2.02e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1067 VIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGKGMVEMIPNAETLRKIqvehgvtGSFKDRPLADW 1146
Cdd:cd05167    52 AIFKVGDDCRQDMLALQLISLFKNIFEEVGLDLYLFPYRVVATGPGCGVIEVIPNSKSRDQI-------GRETDNGLYEY 124

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1147 LQKH--NPGEDEYEKAVENFIYSCAGCCVATYILGICDRHNDNIMLKTTGHMFHIDFGrFlghaqMF-----GNIKRDRA 1219
Cdd:cd05167   125 FLSKygDESTPAFQKARRNFIKSMAGYSLVSYLLQIKDRHNGNIMIDDDGHIIHIDFG-F-----IFeispgGNLGFESA 198

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1220 PFVFTSDMAYVInGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSD--LEDLKyvyDALRPQDTEA 1297
Cdd:cd05167   199 PFKLTKEMVDLM-GGSMESEPFKWFVELCVRGYLAVRPYAEAIVSLVELMLDSGLPCFRGqtIKNLR---ERFALEMSER 274

                         250       260
                  ....*....|....*....|.
gi 157786960 1298 NATTYFTRLIESSLGSVATKL 1318
Cdd:cd05167   275 EAANFMIKLIADSYLKIRTKG 295
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
 1067-1318 2.74e-52

Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 4-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) to generate PtdIns(4)P, the major precursor in the synthesis of other phosphoinositides including PtdIns(4,5)P2, PtdIns(3,4)P2, and PtdIns(3,4,5)P3. There are two types of PI4Ks, types II and III. Type II PI4Ks lack the characteristic catalytic kinase domain present in PI3Ks and type III PI4Ks, and are excluded from this family. Two isoforms of type III PI4K, alpha and beta, exist in most eukaryotes. The PI4K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270626 [Multi-domain]  Cd Length: 286  Bit Score: 185.93  E-value: 2.74e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1067 VIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGKGMVEMIPNAETLRKIQVEHGVTGSFKDrpLADW 1146
Cdd:cd00893    30 LIVKTGDDLKQEQLALQLISQFDQIFKEEGLPLWLRPYEILSLGPDSGIIEMIKNAVSIDSLKKKLDSFNKFVS--LSDF 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1147 LqKHNPGEDEYEKAVENFIYSCAGCCVATYILGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQmfGNIKRDRAPFVFTSD 1226
Cdd:cd00893   108 F-DDNFGDEAIQKARDNFLQSLVAYSLVCYFLQIKDRHNGNILLDKEGHIIHIDFGFFLSSHP--GFYGFEGAPFKLSSE 184

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1227 MAYVIngGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQDTEANATTYFTRL 1306
Cdd:cd00893   185 YIEVL--GGVDSELFKEFRKLFLKGFMALRKHSDKILSLVEMMYSGHGITCFGKKTIQQLKQRFNPELTEGELEVYVLSL 262

                         250
                  ....*....|..
gi 157786960 1307 IESSLGSVATKL 1318
Cdd:cd00893   263 INKSLDNWRTRW 274
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
 1065-1318 2.70e-48

Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 4-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) to generate PtdIns(4)P, the major precursor in the synthesis of other phosphoinositides including PtdIns(4,5)P2, PtdIns(3,4)P2, and PtdIns(3,4,5)P3. Two isoforms of type III PI4K, alpha and beta, exist in most eukaryotes. PI4KIIIbeta (also called Pik1p in yeast) is a 110 kDa protein that is localized to the Golgi and the nucleus. It is required for maintaining the structural integrity of the Golgi complex (GC), and is a key regulator of protein transport from the GC to the plasma membrane. PI4KIIIbeta also functions in the genesis, transport, and exocytosis of synaptic vesicles. The Drosophila PI4KIIIbeta is essential for cytokinesis during spermatogenesis. The PI4K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270712 [Multi-domain]  Cd Length: 292  Bit Score: 174.59  E-value: 2.70e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1065 IRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGKGMVEMIPNAETLRKIQVEHGVTGSFKDRpla 1144
Cdd:cd05168    31 RSVIVKSGDDLRQELLAMQLIKQFQRIFEEAGLPLWLRPYEILVTSSDSGLIETIPDTVSIDSLKKRFPNFTSLLDY--- 107

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1145 dWLQKH-NPGEDEYEKAVENFIYSCAGCCVATYILGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQmfGNIKRDRAPFVF 1223
Cdd:cd05168   108 -FERTFgDPNSERFKEAQRNFVESLAAYSLVCYLLQIKDRHNGNILLDSEGHIIHIDFGFMLSNSP--GGLGFETAPFKL 184

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1224 TSDMAYVINGGDkpSSRFHDFVDLCCQAYNLIRKHTHL------FLNLLGLMLSCGIPELSDLEDLKyvyDALRPQDTEA 1297
Cdd:cd05168   185 TQEYVEVMGGLE--SDMFRYFKTLMIQGFLALRKHADRivllveIMQQGSKLPCFFGGGEFTIEQLR---ERFKLNLTEE 259

                         250       260
                  ....*....|....*....|.
gi 157786960 1298 NATTYFTRLIESSLGSVATKL 1318
Cdd:cd05168   260 ECAQFVDSLIDKSLNNWRTRQ 280
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 800-970 3.09e-47

Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, PI3K class I prefer phosphoinositol (4,5)-bisphosphate as a substrate. Mammalian members interact with active Ras. They form heterodimers with adapter molecules linking them to different signaling pathways.


Pssm-ID: 238444  Cd Length: 171  Bit Score: 167.10  E-value: 3.09e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  800 EEDQRKLKDITQKESLYWLSDADKKQLWEKRYYCHTEVSSLPLVLASApswEWACLPDI---YALLQQWTHMNHQDALGL 876
Cdd:cd00872     1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRKKPQALPKLLLSV---KWNKRDDVaqmYQLLKRWPKLKPEQALEL 77

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  877 LHATFPDQEVRRMAVQWIGSLSDAELLDYLPQLVQALKYECYLDSPLVRFLLKRAISDLRVTHYFFWLLKDSLKDSQFSI 956
Cdd:cd00872    78 LDCNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVSQ 157

                         170
                  ....*....|....
gi 157786960  957 RYQYLLAALLCCCG 970
Cdd:cd00872   158 RFGLLLEAYLRGCG 171
PX_PI3K_C2_alpha cd07289
The phosphoinositide binding Phox Homology Domain of the Alpha Isoform of Class II ...
 1356-1464 4.32e-40

The phosphoinositide binding Phox Homology Domain of the Alpha Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II alpha isoform, PI3K-C2alpha, plays key roles in clathrin assembly and clathrin-mediated membrane trafficking, insulin signaling, vascular smooth muscle contraction, and the priming of neurosecretory granule exocytosis. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


Pssm-ID: 132822  Cd Length: 109  Bit Score: 144.30  E-value: 4.32e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1356 DVFLCRHEKVFHPSKGYIYVVKVMRENAHEATYIQRTFEEFQELHNKLRLLFPSSFLPSFPSRFVIGRSRGEAVAERRKE 1435
Cdd:cd07289     1 EVSVFTYHKRYNPDKHYIYVVRILREGQIEPSFVFRTFDEFQELHNKLSILFPLWKLPGFPNKMVLGRTHIKDVAAKRKV 80

                          90       100
                  ....*....|....*....|....*....
gi 157786960 1436 ELNGYIWHLIHAAPEVAECDLVYTFFHPL 1464
Cdd:cd07289    81 ELNSYIQSLMNSSTEVAECDLVYTFFHPL 109
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 799-977 3.23e-39

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation.


Pssm-ID: 395488  Cd Length: 185  Bit Score: 144.39  E-value: 3.23e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960   799 REEDQRKLKDITQKESLYWLSDADKKQLWEKRYYCHTEVSSLPLVLASApswEWACLPDI---YALLQQWTHMNHQDALG 875
Cdd:pfam00613    6 NEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYLMLVPKALTKLLLSV---KWSDLSEVaeaLSLLLKWAPIDPVDALE 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960   876 LLHATFPDQEVRRMAVQWIGSLSDAELLDYLPQLVQALKYECYLDSPLVRFLLKRAISDLRVTHYFFWLLKDSLKDSQFS 955
Cdd:pfam00613   83 LLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEIHDEEVS 162

                          170       180
                   ....*....|....*....|..
gi 157786960   956 IRYQYLLAALLCCCGKGLREEF 977
Cdd:pfam00613  163 PRFGSLLELYLRSCGTSLLGLN 184
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
 1036-1259 2.30e-38

Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family include PI3K, phosphoinositide 4-kinase (PI4K), PI3K-related protein kinases (PIKKs), and TRansformation/tRanscription domain-Associated Protein (TRAPP). PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives, while PI4K catalyze the phosphorylation of the 4-hydroxyl of PtdIns. PIKKs are protein kinases that catalyze the phosphorylation of serine/threonine residues, especially those that are followed by a glutamine. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI4Ks produce PtdIns(4)P, the major precursor to important signaling phosphoinositides. PIKKs have diverse functions including cell-cycle checkpoints, genome surveillance, mRNA surveillance, and translation control. The PI3K-like catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270621 [Multi-domain]  Cd Length: 216  Bit Score: 143.24  E-value: 2.30e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1036 IVPRDCSYFNSNAVPLKLAFqnVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMRMVIFRCFSTGRGKGM 1115
Cdd:cd00142     3 LDVGILKVIHSKQRPKKITL--IGADGKTYSFLLKRRDDLRKDERSFQFMRLIQSILEKESVNLVLPPYKVIPLSENSGL 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1116 VEMIPNAETLrkiqveHGvtgsfkdrpLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYILGICDRHNDNIMLKTTGH 1195
Cdd:cd00142    81 IEIVKDAQTI------ED---------LLKSLWRKSPSSQSWLNRRENFSCSLAGYSVLGYIFGIGDRHPSNIMIEPSGN 145

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 157786960 1196 MFHIDFGRFLGHAQMfgNIKRDRAPFVFTSDMAYVINGGDKpssrFHDFVDLCCQAYNLIRKHT 1259
Cdd:cd00142   146 IFHIDFGFIFSGRKL--AEGVETVPFRLTPMLENAMGTAGV----NGPFQISMVKIMEILREHA 203
C2C_KIAA1228 cd04030
C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins ...
 1493-1613 3.75e-35

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175996 [Multi-domain]  Cd Length: 127  Bit Score: 130.86  E-value: 3.75e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1493 GEVKLSISY--KNNKLFIMVMHIRGLqPLQDGSD-PDPYVKIYLLPDPQKATKRKTKVARKTCNPTYNEMLVYDgIPKGD 1569
Cdd:cd04030     3 GRIQLTIRYssQRQKLIVTVHKCRNL-PPCDSSDiPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFP-VSLEE 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 157786960 1570 LQQRELQLSVLSEQGF--WENVLLGEVHIRLRELDLAQEKTGWFAL 1613
Cdd:cd04030    81 LKRRTLDVAVKNSKSFlsREKKLLGQVLIDLSDLDLSKGFTQWYDL 126
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 635-775 1.43e-34

Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 domain. Outlier of pfam00168 family.


Pssm-ID: 395640  Cd Length: 136  Bit Score: 129.41  E-value: 1.43e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960   635 SYEEFYLSCSLSHGGKELCSPLQTRRAHFSKylfHLIIWDQQICFPVQVNRLPRETLLCATLYALPIPppgssseanKQK 714
Cdd:pfam00792    1 RQEDLYVECQLYHGGKPLCLPVSTRYVPFSN---SSIKWNEWITFPIQISDLPRSARLCITIWDVSGP---------EKS 68

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 157786960   715 RVPeaLGWVTTPLFNFRQVLTCGRKLLGLWPATQ-ENSSARW---------SAPNFHQPDSViLQIDFPTS 775
Cdd:pfam00792   69 FVP--IGWVNTSLFDKKGILRQGKQKLRLWPSKStPGRSNVDemnrlekllKKYERGQVSSV-DWLDFLTF 136
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 363-465 6.48e-32

PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding pfam00788 domains (unpublished observation).


Pssm-ID: 395642  Cd Length: 106  Bit Score: 120.48  E-value: 6.48e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960   363 TVTPSPEHL--GDEVNLKVTVLCDSLREPLTFTCNCSSTVDLLIYQTLCYTHDELREVDVG-DFVLKPCGLEEFLQNKHA 439
Cdd:pfam00794    1 ASTVSPEPLpkLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVTdDYVLKVCGRDEYLLGDHP 80

                           90       100
                   ....*....|....*....|....*.
gi 157786960   440 LGSHEYIQHCRKFDINIRLQLMEQKA 465
Cdd:pfam00794   81 LGQFEYIRNCLKSGREPHLTLVEQSS 106
PX_PI3K_C2_68D cd06884
The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases ...
 1363-1464 5.33e-31

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases similar to the Drosophila PI3K_68D protein; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. PI3K_68D is a novel PI3K which is widely expressed throughout the Drosophila life cycle. In vitro, it has been shown to phosphorylate PI and PI4P. It is involved in signaling pathways that affect pattern formation of Drosophila wings.


Pssm-ID: 132794  Cd Length: 111  Bit Score: 118.29  E-value: 5.33e-31
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1363 EKVFHPSKGYIYVVKVMRENAHEATYIQRTFEEFQELHNKLRLLFPSSFLPSFPSRFVIGRSRGEAVAERRKEELNGYIW 1442
Cdd:cd06884    10 QKRYDPEKYYVYVVEVTRENQASPQHVFRTYKEFLELYQKLCRKFPLAKLHPLSTGSHVGRSNIKSVAEKRKQDIQQFLN 89

                          90       100
                  ....*....|....*....|..
gi 157786960 1443 HLIHAAPEVAECDLVYTFFHPL 1464
Cdd:cd06884    90 SLFKMAEEVSHSDLVYTFFHPL 111
C2A_SLP cd08521
C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share ...
 1493-1613 2.05e-30

C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. 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: 176056 [Multi-domain]  Cd Length: 123  Bit Score: 116.97  E-value: 2.05e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1493 GEVKLSISY--KNNKLFIMVMHIRGLQPLQDGSD-PDPYVKIYLLPDPQKATKRKTKVARKTCNPTYNEMLVYDgIPKGD 1569
Cdd:cd08521     1 GEIEFSLSYnyKTGSLEVHIKECRNLAYADEKKKrSNPYVKVYLLPDKSKQSKRKTSVKKNTTNPVFNETLKYH-ISKSQ 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 157786960 1570 LQQRELQLSVLSEQGFWENVLLGEVHIRLRELDLAQEKTGWFAL 1613
Cdd:cd08521    80 LETRTLQLSVWHHDRFGRNTFLGEVEIPLDSWDLDSQQSEWYPL 123
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
1049-1328 8.88e-30

Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 129.90  E-value: 8.88e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1049 VPLKLAFQNVDplGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEGLDMR----MVIFRCFSTGRGKGMVEMIPNAET 1124
Cdd:COG5032  1783 RPRRLTIRGSD--GKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKETRRrdlwIRPYKVIPLSPGSGIIEWVPNSDT 1860

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1125 LRKI--------------------QVEHGVTG---------SFKDRP-LADWLQKHNPGEDEYEKAVENFIYSCAGCCVA 1174
Cdd:COG5032  1861 LHSIlreyhkrknisidqekklaaRLDNLKLLlkdefftkaTLKSPPvLYDWFSESFPNPEDWLTARTNFARSLAVYSVI 1940

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1175 TYILGICDRHNDNIML-KTTGHMFHIDFGRFLGhAQMFGNIKRDRAPFVFTSDMAYVING-GDKPSsrfhdFVDLCCQAY 1252
Cdd:COG5032  1941 GYILGLGDRHPGNILIdRSSGHVIHIDFGFILF-NAPGRFPFPEKVPFRLTRNIVEAMGVsGVEGS-----FRELCETAF 2014

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1253 NLIRKHTHL------FLNLLGLMLSCGIPELSD--LEDLKYVYDALRPQDTEANATTYFTRLIESSLGSVATKL-NFFih 1323
Cdd:COG5032  2015 RALRKNADSlmnvleLFVRDPLIEWRRLPCFREiqNNEIVNVLERFRLKLSEKDAEKFVDLLINKSVESLITQAtDPF-- 2092


                  ....*
gi 157786960 1324 NLAQM 1328
Cdd:COG5032  2093 QLATM 2097
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 608-709 4.14e-27

Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.


Pssm-ID: 214536  Cd Length: 100  Bit Score: 106.66  E-value: 4.14e-27
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960    608 VQEACHFSGALAFTVYGTHRIPIIWATSYEEFYLSCSLSHGGKELCSPLQTRRAHFSKYlfhlIIWDQQICFPVQVNRLP 687
Cdd:smart00142    3 IESLWDCDRNLVITIALIHGIPLNWSRDYSDLYVEIQLYHGGKLLCLPVSTSYKPFFPS----VKWNEWLTFPIQISDLP 78

                            90       100
                    ....*....|....*....|..
gi 157786960    688 RETLLCATLYALPIPPPGSSSE 709
Cdd:smart00142   79 REARLCITIYAVKNPSKGSEFG 100
C2A_SLP-1_2 cd08393
C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members ...
 1493-1613 3.17e-26

C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike Slp3 and Slp4/granuphilin which are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. 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: 176039 [Multi-domain]  Cd Length: 125  Bit Score: 105.21  E-value: 3.17e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1493 GEVKLSISY--KNNKLFIMVMHIRGLQPLQDGSD-PDPYVKIYLLPDPQKATKRKTKVARKTCNPTYNEMLVYDgIPKGD 1569
Cdd:cd08393     2 GSVQFALDYdpKLRELHVHVIQCQDLAAADPKKQrSDPYVKTYLLPDKSNRGKRKTSVKKKTLNPVFNETLRYK-VEREE 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 157786960 1570 LQQRELQLSVLSEQGFWENVLLGEVHIRLRELDLAQEKTGWFAL 1613
Cdd:cd08393    81 LPTRVLNLSVWHRDSLGRNSFLGEVEVDLGSWDWSNTQPTWYPL 124
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 1491-1598 9.33e-26

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: 103.87  E-value: 9.33e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1491 VGGEVKLSISY--KNNKLFIMVMHIRGLQPLQDGSDPDPYVKIYLLPDPQKATKRKTKVARKTCNPTYNEMLVYDGIPKG 1568
Cdd:cd04031     1 ITGRIQIQLWYdkVTSQLIVTVLQARDLPPRDDGSLRNPYVKVYLLPDRSEKSKRRTKTVKKTLNPEWNQTFEYSNVRRE 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 157786960 1569 DLQQRELQLSVLSEQGFWENVLLGEVHIRL 1598
Cdd:cd04031    81 TLKERTLEVTVWDYDRDGENDFLGEVVIDL 110
PI3Ka_III cd00870
Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is ...
 801-951 7.51e-25

Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is conserved in all PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. In general, PI3Ks class III phosphorylate phosphoinositol (PtdIns) only. The prototypical PI3K class III, yeast Vps34, is involved in trafficking proteins from Golgi to the vacuole.


Pssm-ID: 238442  Cd Length: 166  Bit Score: 102.79  E-value: 7.51e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  801 EDQRKLKDITQKESLYWLSDADKKQLWEKRYYCHTEVSSLPLVLASApswEWACLPDI---YALLQQWTHMNHQDALGLL 877
Cdd:cd00870     9 KERKELNKILKYPPTTKLTDEEKDLIWKFRFYLTNNKKALTKFLKSV---NWSDEQEVkqaLELMPKWAKIDIEDALELL 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  878 HATFPDQEVRRMAVQWIGSLSDAELLDYLPQLVQALKYECY-------LDSPLVRFLLKRAISDLRVTHYFFWLLKDSLK 950
Cdd:cd00870    86 SPYFTNPVVRKYAVSRLKLASDEELLLYLLQLVQALKYENLdlsplprLDSPLADFLIERALKNPKLANFLYWYLKVELE 165


                  .
gi 157786960  951 D 951
Cdd:cd00870   166 D 166
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
 1493-1610 2.66e-24

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175987 [Multi-domain]  Cd Length: 162  Bit Score: 100.86  E-value: 2.66e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1493 GEVKLSISY--------------KNNKLFIMVMHIRGLQPLQDGSDPDPYVKIYLLPDPQKATKRKTKVARKTCNPTYNE 1558
Cdd:cd04020     2 GELKVALKYvppesegalkskkpSTGELHVWVKEAKNLPALKSGGTSDSFVKCYLLPDKSKKSKQKTPVVKKSVNPVWNH 81

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 157786960 1559 MLVYDGIPKGDLQQRELQLSVLSEQGFWENVLLGEVHIRLRELDLAQEKTGW 1610
Cdd:cd04020    82 TFVYDGVSPEDLSQACLELTVWDHDKLSSNDFLGGVRLGLGTGKSYGQAVDW 133
C2A_SLP-4_5 cd04029
C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members ...
 1493-1613 7.01e-24

C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp4/granuphilin promotes dense-core vesicle exocytosis. The C2A domain of Slp4 is Ca2+ dependent. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. 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: 175995 [Multi-domain]  Cd Length: 125  Bit Score: 98.28  E-value: 7.01e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1493 GEVKLSISY--KNNKLFIMVMHIRGLQPLQDGSD-PDPYVKIYLLPDPQKATKRKTKVARKTCNPTYNEMLVYDgIPKGD 1569
Cdd:cd04029     2 GEILFSLSYdyKTQSLNVHVKECRNLAYGDEAKKrSNPYVKTYLLPDKSRQSKRKTSIKRNTTNPVYNETLKYS-ISHSQ 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 157786960 1570 LQQRELQLSVLSEQGFWENVLLGEVHIRLRELDLAQEKTGWFAL 1613
Cdd:cd04029    81 LETRTLQLSVWHYDRFGRNTFLGEVEIPLDSWNFDSQHEECLPL 124
PX smart00312
PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function ...
 1366-1462 9.91e-24

PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function present in phox proteins, PLD isoforms, a PI3K isoform.


Pssm-ID: 214610  Cd Length: 105  Bit Score: 97.41  E-value: 9.91e-24
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960   1366 FHPSKGYIYVVKVMRENAHEATYIQRTFEEFQELHNKLRLLFPSSFLPSFPSRFVIGRSR--GEAVAERRKEELNGYIWH 1443
Cdd:smart00312    7 IGDGKHYYYVIEIETKTGLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRLNnfSEEFIEKRRRGLEKYLQS 86

                            90
                    ....*....|....*....
gi 157786960   1444 LIHAAPEVAECDLVYTFFH 1462
Cdd:smart00312   87 LLNHPELINHSEVVLEFLE 105
C2 pfam00168
C2 domain;
1504-1613 1.23e-23

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 97.00  E-value: 1.23e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  1504 NKLFIMVMHIRGLQPLQDGSDPDPYVKIYLLpdpQKATKRKTKVARKTCNPTYNEMLVYDgIPkgDLQQRELQLSVLSEQ 1583
Cdd:pfam00168    1 GRLTVTVIEAKNLPPKDGNGTSDPYVKVYLL---DGKQKKKTKVVKNTLNPVWNETFTFS-VP--DPENAVLEIEVYDYD 74

                           90       100       110
                   ....*....|....*....|....*....|
gi 157786960  1584 GFWENVLLGEVHIRLRELDLAQEKTGWFAL 1613
Cdd:pfam00168   75 RFGRDDFIGEVRIPLSELDSGEGLDGWYPL 104
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 1493-1613 1.04e-22

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


Pssm-ID: 176032 [Multi-domain]  Cd Length: 125  Bit Score: 95.09  E-value: 1.04e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1493 GEVKLSISYKNNKLFIMVMHIRGLQ-PLQDGS-DPDPYVKIYLLPDPQKatKRKTKVARKTCNPTYNEMLVYDGIPKGDL 1570
Cdd:cd08386     3 GRIQFSVSYDFQESTLTLKILKAVElPAKDFSgTSDPFVKIYLLPDKKH--KLETKVKRKNLNPHWNETFLFEGFPYEKL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 157786960 1571 QQRELQLSVLSEQGFWENVLLGEVHIRLRELDLAQEKTGWFAL 1613
Cdd:cd08386    81 QQRVLYLQVLDYDRFSRNDPIGEVSLPLNKVDLTEEQTFWKDL 123
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 1505-1610 3.92e-22

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 92.55  E-value: 3.92e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960   1505 KLFIMVMHIRGLQPLQDGSDPDPYVKIYLLPDPQKatKRKTKVARKTCNPTYNEMLVYDGIPkgdLQQRELQLSVLSEQG 1584
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGKSDPYVKVSLDGDPKE--KKKTKVVKNTLNPVWNETFEFEVPP---PELAELEIEVYDKDR 75

                            90       100
                    ....*....|....*....|....*.
gi 157786960   1585 FWENVLLGEVHIRLRELDLAQEKTGW 1610
Cdd:smart00239   76 FGRDDFIGQVTIPLSDLLLGGRHEKL 101
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 1493-1608 4.47e-22

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


Pssm-ID: 176000 [Multi-domain]  Cd Length: 123  Bit Score: 93.12  E-value: 4.47e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1493 GEVKLSISY--KNNKLFIMVMHIRGLQPLQDGSDPDPYVKIYLLPDPQKATKRKTKVARKTCNPTYNEMLVYDGIPKGDL 1570
Cdd:cd04035     2 GTLEFTLLYdpANSALHCTIIRAKGLKAMDANGLSDPYVKLNLLPGASKATKLRTKTVHKTRNPEFNETLTYYGITEEDI 81

                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 157786960 1571 QQRELQLSVLSEQGFwENVLLGEVHIRLRELDLAQEKT 1608
Cdd:cd04035    82 QRKTLRLLVLDEDRF-GNDFLGETRIPLKKLKPNQTKQ 118
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 1493-1619 4.99e-20

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: 87.70  E-value: 4.99e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1493 GEVKLSISYKNNKLFIMVMHIRGLQPLqdgsDP----DPYVKIYLLPDPQKATKRKTKVARKTCNPTYNEMLVYDgIPKG 1568
Cdd:cd04026     2 GRIYLKISVKDNKLTVEVREAKNLIPM----DPnglsDPYVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTFD-LKPA 76

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 157786960 1569 DLQQReLQLSVLSEQGFWENVLLGEVHIRLRELdLAQEKTGWFALGSRGHG 1619
Cdd:cd04026    77 DKDRR-LSIEVWDWDRTTRNDFMGSLSFGVSEL-IKMPVDGWYKLLNQEEG 125
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
 1493-1615 1.68e-19

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis as do synaptotagmins 5, 6, and 10. It is distinguished from the other synaptotagmins by having an N-glycosylated N-terminus. Synaptotagmins 5, 6, and 10, members of class 3 synaptotagmins, are located primarily in the brain and localized to the active zone and plasma membrane. They is distinguished from the other synaptotagmins by having disulfide bonds at its N-terminus. Synaptotagmin 6 also regulates the acrosome reaction, a unique Ca2+-regulated exocytosis, in sperm. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176031 [Multi-domain]  Cd Length: 124  Bit Score: 85.78  E-value: 1.68e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1493 GEVKLSISY--KNNKLFIMVMHIRGLQPLQDGSDPDPYVKIYLLPDPQKatKRKTKVARKTCNPTYNEMLVYDgIPKGDL 1570
Cdd:cd08385     3 GKLQFSLDYdfQSNQLTVGIIQAADLPAMDMGGTSDPYVKVYLLPDKKK--KFETKVHRKTLNPVFNETFTFK-VPYSEL 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 157786960 1571 QQRELQLSVLSEQGFWENVLLGEVHIRLRELDLAQEKTGWFALGS 1615
Cdd:cd08385    80 GNKTLVFSVYDFDRFSKHDLIGEVRVPLLTVDLGHVTEEWRDLES 124
C2A_Synaptotagmin-15-17 cd08390
C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...
 1498-1613 3.12e-19

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: 85.00  E-value: 3.12e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1498 SISYKN--NKLFIMVMHIRGLQPLQDGSDP-DPYVKIYLLPDPQKAtkRKTKVARKTCNPTYNEMLVYDgIPKGDLQQRE 1574
Cdd:cd08390     6 SVQYDLeeEQLTVSLIKARNLPPRTKDVAHcDPFVKVCLLPDERRS--LQSKVKRKTQNPNFDETFVFQ-VSFKELQRRT 82

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 157786960 1575 LQLSVLSEQGFWENVLLGEVHIRLRELDLAQEKTGWFAL 1613
Cdd:cd08390    83 LRLSVYDVDRFSRHCIIGHVLFPLKDLDLVKGGVVWRDL 121
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 1493-1594 4.06e-19

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: 84.94  E-value: 4.06e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1493 GEVKLSISY--KNNKLFIMVMHIRGLQPLQDGSDPDPYVKIYLLPDPQKATKRKTKVARKTCNPTYNEMLVYDgIPKGDL 1570
Cdd:cd00276     1 GELLLSLSYlpTAERLTVVVLKARNLPPSDGKGLSDPYVKVSLLQGGKKLKKKKTSVKKGTLNPVFNEAFSFD-VPAEQL 79

                          90       100
                  ....*....|....*....|....
gi 157786960 1571 QQRELQLSVLSEQGFWENVLLGEV 1594
Cdd:cd00276    80 EEVSLVITVVDKDSVGRNEVIGQV 103
C2B_RIM1alpha cd04028
C2 domain second repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 1493-1613 1.09e-18

C2 domain second 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: 175994 [Multi-domain]  Cd Length: 146  Bit Score: 84.36  E-value: 1.09e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1493 GEVKLSISYKNNKLFIMVMHIRGLQPlQDGSD--PDPYVKIYLLPDPQKATKRKTKVARKTCNPTYNEMLVYDGIPKGdl 1570
Cdd:cd04028    18 GDIQLGLYDKKGQLEVEVIRARGLVQ-KPGSKvlPAPYVKVYLLEGKKCIAKKKTKIARKTLDPLYQQQLVFDVSPTG-- 94

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 157786960 1571 qqRELQLSVLSEQGFWEN-VLLGEVHIRLRELDLAQEKTGWFAL 1613
Cdd:cd04028    95 --KTLQVIVWGDYGRMDKkVFMGVAQILLDDLDLSNLVIGWYKL 136
C2_PI3K_like cd08380
C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes ...
 639-778 2.64e-18

C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes of PI3Ks. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. In addition some PI3Ks contain a Ras-binding domain and/or a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. 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 members with the first C2 repeat, C2A, and a type-I topology, as well as some with a single C2 repeat.


Pssm-ID: 176026  Cd Length: 156  Bit Score: 83.56  E-value: 2.64e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  639 FYLSCSLSHGGKELCSPLQTRRAHFSKYLFhliiWDQQICFPVQVNRLPRETLLCATLYAlpipppgsSSEANKQKRVPe 718
Cdd:cd08380    30 LYVRVQLYHGGEPLCPPQSTKKVPFSTSVT----WNEWLTFDILISDLPREARLCLSIYA--------VSEPGSKKEVP- 96

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 157786960  719 aLGWVTTPLFNFRQVLTCGRKLLGLWPAT-QENSSArwsAPNFHQPDSVILQIDFPTSAFD 778
Cdd:cd08380    97 -LGWVNVPLFDYKGKLRQGMITLNLWPGKkTDPRIA---CTPCNNSNENSTRLLIELPEFS 153
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 1506-1613 8.25e-17

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: 77.49  E-value: 8.25e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1506 LFIMVMHIRGLQPLQDGSDPDPYVKIYLLPDpqkaTKRKTKVARKTCNPTYNEMLVydgIPKGDLQQRELQLSVLSEQGF 1585
Cdd:cd00030     1 LRVTVIEARNLPAKDLNGKSDPYVKVSLGGK----QKFKTKVVKNTLNPVWNETFE---FPVLDPESDTLTVEVWDKDRF 73

                          90       100
                  ....*....|....*....|....*....
gi 157786960 1586 WENVLLGEVHIRLREL-DLAQEKTGWFAL 1613
Cdd:cd00030    74 SKDDFLGEVEIPLSELlDSGKEGELWLPL 102
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 363-463 1.43e-16

PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding RA domains (unpublished observation).


Pssm-ID: 197540  Cd Length: 108  Bit Score: 76.98  E-value: 1.43e-16
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960    363 TVTPSPEHLGDEV---NLKVTVLCDSLREPLTFTCNCSSTVDLLIYQTLCYTHDELREVDVG--DFVLKPCGLEEFLQNK 437
Cdd:smart00144    1 TSPSVPEPLPLKTianKILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQVDPTseDYILKVCGRDEYLLGD 80

                            90       100
                    ....*....|....*....|....*.
gi 157786960    438 HALGSHEYIQHCRKFDINIRLQLMEQ 463
Cdd:smart00144   81 HPLGSFEYIRNCLKNGTEPHLVLMTL 106
PX pfam00787
PX domain; PX domains bind to phosphoinositides.
 1389-1463 3.16e-16

PX domain; PX domains bind to phosphoinositides.


Pssm-ID: 459940  Cd Length: 84  Bit Score: 74.97  E-value: 3.16e-16
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 157786960  1389 IQRTFEEFQELHNKLRLLFPSSFLPSFPSRFVIGRSRgEAVAERRKEELNGYIWHLIHaAPEVAECDLVYTFFHP 1463
Cdd:pfam00787   11 VRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLGRYN-EEFIEKRRKGLEQYLQRLLQ-HPELRNSEVLLEFLES 83
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 1495-1579 7.59e-16

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: 75.85  E-value: 7.59e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1495 VKLSISY--KNNKLFIMVMHIRGLQPLQDGSDPDPYVKIYLLPDPQKATKRKTKVARKTCNPTYNEMLVYDgIPKGDLQQ 1572
Cdd:cd08384     2 ILVSLMYntQRRGLIVGIIRCVNLAAMDANGYSDPFVKLYLKPDAGKKSKHKTQVKKKTLNPEFNEEFFYD-IKHSDLAK 80


                  ....*..
gi 157786960 1573 RELQLSV 1579
Cdd:cd08384    81 KTLEITV 87
PIKKc_DNA-PK cd05172
Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, ...
 1068-1211 6.08e-15

Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, containing the Ku70/80 subunit, and a catalytic subunit, which contains a NUC194 domain of unknown function, a FAT (FRAP, ATM and TRRAP) domain, a catalytic domain, and a FATC domain at the C-terminus. It is part of a multi-component system involved in non-homologous end joining (NHEJ), a process of repairing double strand breaks (DSBs) by joining together two free DNA ends of little homology. DNA-PK functions as a molecular sensor for DNA damage that enhances the signal via phosphorylation of downstream targets. It may also act as a protein scaffold that aids the localization of DNA repair proteins to the site of DNA damage. DNA-PK also plays a role in the maintenance of telomeric stability and the prevention of chromosomal end fusion. DNA-PK is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The DNA-PK catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270716 [Multi-domain]  Cd Length: 235  Bit Score: 76.07  E-value: 6.08e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1068 IFKCGDDLRQDMLTLQMIRIMSKIWVQE----GLDMRMVIFRCFSTGRGKGMVEMIPNAETLRKIqvehgvtgsFKDRPL 1143
Cdd:cd05172    33 LVKGGEDLRQDQRIQQLFDVMNNILASDpacrQRRLRIRTYQVIPMTSRLGLIEWVDNTTPLKEI---------LENDLL 103

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 157786960 1144 ADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYILGICDRHNDNIML-KTTGHMFHIDFGRFLGHAQMF 1211
Cdd:cd05172   104 RRALLSLASSPEAFLALRSNFARSLAAMSICGYILGIGDRHLSNFLVdLSTGRLIGIDFGHAFGSATQF 172
C2A_SLP-3 cd08392
C2 domain first repeat present in Synaptotagmin-like protein 3; All Slp members basically ...
 1493-1603 6.51e-15

C2 domain first repeat present in Synaptotagmin-like protein 3; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. Little is known about the expression or localization of Slp3. The C2A domain of Slp3 is Ca2+ dependent. It has been demonstrated that Slp3 promotes dense-core vesicle exocytosis. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176038 [Multi-domain]  Cd Length: 128  Bit Score: 72.94  E-value: 6.51e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1493 GEVKLSISYkNNKLFIMVMHIRGLQPLQDGSDP----DPYVKIYLLPDPQKATKRKTKVARKTCNPTYNEMLVYDgIPKG 1568
Cdd:cd08392     2 GEIEFALHY-NFRTSCLEITIKACRNLAYGDEKkkkcHPYVKVCLLPDKSHNSKRKTAVKKGTVNPVFNETLKYV-VEAD 79

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 157786960 1569 DLQQRELQLSVLSEQGFWENVLLGEVHIRLRELDL 1603
Cdd:cd08392    80 LLSSRQLQVSVWHSRTLKRRVFLGEVLIPLADWDF 114
C2A_Synaptotagmin-4-11 cd08388
C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a ...
 1493-1608 6.71e-15

C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmins 4 and 11, class 4 synaptotagmins, are located in the brain. Their functions are unknown. They are distinguished from the other synaptotagmins by having and Asp to Ser substitution in their C2A domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176034 [Multi-domain]  Cd Length: 128  Bit Score: 72.77  E-value: 6.71e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1493 GEVKLSISYKNNKLFIMVMHI--RGLQPL--QDGSDpDPYVKIYLLPDpqKATKRKTKVARKTCNPTYNEMLVYDGIPKG 1568
Cdd:cd08388     3 GTLFFSLRYNSEKKALLVNIIecRDLPAMdeQSGTS-DPYVKLQLLPE--KEHKVKTRVLRKTRNPVYDETFTFYGIPYN 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 157786960 1569 DLQQRELQLSVLSEQGFWENVLLGEVHIRLRELDLAQEKT 1608
Cdd:cd08388    80 QLQDLSLHFAVLSFDRYSRDDVIGEVVCPLAGADLLNEGE 119
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
 1044-1227 9.70e-15

Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members include ATM (Ataxia telangiectasia mutated), ATR (Ataxia telangiectasia and Rad3-related), TOR (Target of rapamycin), SMG-1 (Suppressor of morphogenetic effect on genitalia-1), and DNA-PK (DNA-dependent protein kinase). PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). They show strong preference for phosphorylating serine/threonine residues followed by a glutamine and are also referred to as (S/T)-Q-directed kinases. They all contain a FATC (FRAP, ATM and TRRAP, C-terminal) domain. PIKKs have diverse functions including cell-cycle checkpoints, genome surveillance, mRNA surveillance, and translation control. The PIKK catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270708 [Multi-domain]  Cd Length: 222  Bit Score: 75.00  E-value: 9.70e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1044 FNSNAVPLKLAFQNVDplGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQEG----LDMRMVIFRCFSTGRGKGMVEMI 1119
Cdd:cd05164    11 LASLQKPKKITILGSD--GKEYPFLVKGDDDLRKDERVMQLFQLLNTLLEKDKetrkRNLTIRTYSVVPLSSQSGLIEWV 88

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1120 PNAETLRKIqvehgvtgsfkdrpLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYILGICDRHNDNIMLKT-TGHMFH 1198
Cdd:cd05164    89 DNTTTLKPV--------------LKKWFNETFPDPTQWYEARSNYTKSTAVMSMVGYIIGLGDRHLENILIDTkTGEVVH 154

                         170       180
                  ....*....|....*....|....*....
gi 157786960 1199 IDFGRFLGHAQMFGniKRDRAPFVFTSDM 1227
Cdd:cd05164   155 IDFGMIFNKGKTLP--VPEIVPFRLTRNI 181
C2A_Synaptotagmin-8 cd08387
C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...
 1493-1615 2.09e-14

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: 71.28  E-value: 2.09e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1493 GEVKLSISYKNNK--LFIMVMHIRGLQPLQDGSDPDPYVKIYLLPDpqKATKRKTKVARKTCNPTYNEMLVYdGIPKGDL 1570
Cdd:cd08387     3 GELHFSLEYDKDMgiLNVKLIQARNLQPRDFSGTADPYCKVRLLPD--RSNTKQSKIHKKTLNPEFDESFVF-EVPPQEL 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 157786960 1571 QQRELQLSVLSEQGFWENVLLGEVHIRLRELDLAQEKTGWFALGS 1615
Cdd:cd08387    80 PKRTLEVLLYDFDQFSRDECIGVVELPLAEVDLSEKLDLWRKIQS 124
C2B_Synaptotagmin-4 cd08404
C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...
 1493-1618 5.10e-14

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: 70.53  E-value: 5.10e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1493 GEVKLSISYK--NNKLFIMVMHIRGLQPLQDGSDPDPYVKIYLLPDPQKATKRKTKVARKTCNPTYNEMLVYDgIPKGDL 1570
Cdd:cd08404     2 GELLLSLCYQptTNRLTVVVLKARHLPKMDVSGLADPYVKVNLYYGKKRISKKKTHVKKCTLNPVFNESFVFD-IPSEEL 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 157786960 1571 QQRELQLSVLSeqgfWENVLLGEVHIRLREldlaqektGWFALGSRGH 1618
Cdd:cd08404    81 EDISVEFLVLD----SDRVTKNEVIGRLVL--------GPKASGSGGH 116
PX_domain cd06093
The Phox Homology domain, a phosphoinositide binding module; The PX domain is a ...
 1356-1461 1.04e-13

The Phox Homology domain, a phosphoinositide binding module; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to membranes. Proteins containing PX domains interact with PIs and have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. Many members of this superfamily bind phosphatidylinositol-3-phosphate (PI3P) but in some cases, other PIs such as PI4P or PI(3,4)P2, among others, are the preferred substrates. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction, as in the cases of p40phox, p47phox, and some sorting nexins (SNXs). The PX domain is conserved from yeast to humans and is found in more than 100 proteins. The majority of PX domain-containing proteins are SNXs, which play important roles in endosomal sorting.


Pssm-ID: 132768 [Multi-domain]  Cd Length: 106  Bit Score: 68.54  E-value: 1.04e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1356 DVFLCRHEKVFHPSKGYI-YVVKVMRENAHEATyIQRTFEEFQELHNKLRLLFPSSFLPSFPSRFVIGRSRGEaVAERRK 1434
Cdd:cd06093     1 SVSIPDYEKVKDGGKKYVvYIIEVTTQGGEEWT-VYRRYSDFEELHEKLKKKFPGVILPPLPPKKLFGNLDPE-FIEERR 78

                          90       100
                  ....*....|....*....|....*..
gi 157786960 1435 EELNGYIWHLIHaAPEVAECDLVYTFF 1461
Cdd:cd06093    79 KQLEQYLQSLLN-HPELRNSEELKEFL 104
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 1493-1600 6.17e-12

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: 64.75  E-value: 6.17e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1493 GEVKLSISYK--NNKLFIMVMHIRGLQPLQDGSDPDPYVKIYLLPDPQKATKRKTKVARKTCNPTYNEMLVYDgIPKGDL 1570
Cdd:cd08405     2 GELLLSLCYNptANRITVNIIKARNLKAMDINGTSDPYVKVWLMYKDKRVEKKKTVIKKRTLNPVFNESFIFN-IPLERL 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 157786960 1571 QQRELQLSVLSEQGFWENVLLGEVHIRLRE 1600
Cdd:cd08405    81 RETTLIITVMDKDRLSRNDLIGKIYLGWKS 110
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 1044-1201 9.04e-12

Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to as Mei-41 (Drosophila), Esr1/Mec1p (Saccharomyces cerevisiae), Rad3 (Schizosaccharomyces pombe), and FRAP-related protein (human). ATR contains a UME domain of unknown function, a FAT (FRAP, ATM and TRRAP) domain, a catalytic domain, and a FATC domain at the C-terminus. Together with its downstream effector kinase, Chk1, ATR plays a central role in regulating the replication checkpoint. ATR stabilizes replication forks by promoting the association of DNA polymerases with the fork. Preventing fork collapse is essential in preserving genomic integrity. ATR also plays a role in normal cell growth and in response to DNA damage. ATR is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The ATR catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270625 [Multi-domain]  Cd Length: 237  Bit Score: 66.76  E-value: 9.04e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1044 FNSNAVPLKLAFQNVDplGENIRVIFKCGDDLRQDMLTLQMIRIMSKIWVQ--EGLDMRMVIfRCFST---GRGKGMVEM 1118
Cdd:cd00892    11 MPSLQKPKKITLVGSD--GKKYPFLCKPKDDLRKDARMMEFNTLINRLLSKdpESRRRNLHI-RTYAViplNEECGIIEW 87

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1119 IPNAETLRKIqvehgVTGSFKDRpLADWLQKHNPGEDEYEKAVENFIYSCAGCCVATYILGICDRHNDNIML-KTTGHMF 1197
Cdd:cd00892    88 VPNTVTLRSI-----LSTLYPPV-LHEWFLKNFPDPTAWYEARNNYTRSTAVMSMVGYILGLGDRHGENILFdSTTGDVV 161


                  ....
gi 157786960 1198 HIDF 1201
Cdd:cd00892   162 HVDF 165
C2B_Synaptotagmin-1 cd08402
C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...
 1493-1594 9.28e-12

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: 63.96  E-value: 9.28e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1493 GEVKLSISY--KNNKLFIMVMHIRGLQPLQDGSDPDPYVKIYLLPDPQKATKRKTKVARKTCNPTYNEMLVYDgIPKGDL 1570
Cdd:cd08402     2 GDICFSLRYvpTAGKLTVVILEAKNLKKMDVGGLSDPYVKIHLMQNGKRLKKKKTTIKKRTLNPYYNESFSFE-VPFEQI 80

                          90       100
                  ....*....|....*....|....
gi 157786960 1571 QQRELQLSVLSEQGFWENVLLGEV 1594
Cdd:cd08402    81 QKVHLIVTVLDYDRIGKNDPIGKV 104
C2B_Synaptotagmin-3-5-6-9-10 cd08403
C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a ...
 1493-1596 9.66e-12

C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 3, a member of class 3 synaptotagmins, is located in the brain and localized to the active zone and plasma membrane. It functions as a Ca2+ sensor for fast exocytosis. It, along with synaptotagmins 5,6, and 10, has disulfide bonds at its N-terminus. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176048 [Multi-domain]  Cd Length: 134  Bit Score: 64.07  E-value: 9.66e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1493 GEVKLSISY--KNNKLFIMVMHIRGLQPLQDGSDPDPYVKIYLLPDPQKATKRKTKVARKTCNPTYNEMLVYDgIPKGDL 1570
Cdd:cd08403     1 GELMFSLCYlpTAGRLTLTIIKARNLKAMDITGFSDPYVKVSLMCEGRRLKKKKTSVKKNTLNPTYNEALVFD-VPPENV 79

                          90       100
                  ....*....|....*....|....*.
gi 157786960 1571 QQRELQLSVLSEQGFWENVLLGEVHI 1596
Cdd:cd08403    80 DNVSLIIAVVDYDRVGHNELIGVCRV 105
PX_FISH cd06888
The phosphoinositide binding Phox Homology domain of Five SH protein; The PX domain is a ...
 1354-1463 1.22e-11

The phosphoinositide binding Phox Homology domain of Five SH protein; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Five SH (FISH), also called Tks5, is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. FISH contains an N-terminal PX domain and five Src homology 3 (SH3) domains. FISH binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. This subfamily also includes proteins with a different number of SH3 domains than FISH, such as Tks4, which contains four SH3 domains instead of five. The Tks4 adaptor protein is required for the formation of functional podosomes. It has overlapping, but not identical, functions as FISH. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


Pssm-ID: 132798  Cd Length: 119  Bit Score: 63.21  E-value: 1.22e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1354 IRDVFLCRHEKVFHPSKGYIYVVKVMRENAHEATyIQRTFEEFQELHNKLRLLFP---------SSFLPSFPSRFVIGRS 1424
Cdd:cd06888     1 VKDVKVIDVEKRRAPSKHYVYIINVTWSDGSSNV-IYRRYSKFFDLQMQLLDKFPieggqkdpsQRIIPFLPGKILFRRS 79

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 157786960 1425 RGEAVAERRKEELNGYIWHLIHAAPEVAECDLVYTFFHP 1463
Cdd:cd06888    80 HIRDVAVKRLKPIDEYCKALVRLPPHISQCDEVLRFFEA 118
C2_RGS-like cd08685
C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of ...
 1493-1613 8.10e-11

C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of the regulator of G-protein signaling (RGS) family. RGS is a GTPase activating protein which inhibits G-protein mediated signal transduction. The protein is largely cytosolic, but G-protein activation leads to translocation of this protein to the plasma membrane. A nuclear form of this protein has also been described, but its sequence has not been identified. There are multiple alternatively spliced transcript variants in this family with some members having additional domains (ex. PDZ and RGS) downstream of the 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: 176067 [Multi-domain]  Cd Length: 119  Bit Score: 60.93  E-value: 8.10e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1493 GEVKLSISYKNNKLFIMVMHIRGLQPLQDGSDpDPYVKIYLLPDPQKATKRKTKVARKTCNPTYNEMLVYDgIPKGDLQQ 1572
Cdd:cd08685     1 GQLKLSIEGQNRKLTLHVLEAKGLRSTNSGTC-NSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSFD-VNERDYQK 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 157786960 1573 RELQLSVLSEQGFWENVLLGEVHIRLRELDLAQEKTGWFAL 1613
Cdd:cd08685    79 RLLVTVWNKLSKSRDSGLLGCMSFGVKSIVNQKEISGWYYL 119
C2B_Synaptotagmin-12 cd08406
C2 domain second repeat present in Synaptotagmin 12; Synaptotagmin is a membrane-trafficking ...
 1493-1579 8.42e-11

C2 domain second repeat present in Synaptotagmin 12; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 12, a member of class 6 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmins 8 and 13, do not have any consensus Ca2+ binding sites. 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: 176051 [Multi-domain]  Cd Length: 136  Bit Score: 61.35  E-value: 8.42e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1493 GEVKLSISY--KNNKLFIMVMHIRGLQPLQDGSDPDPYVKIYLLPDPQKATKRKTKVARKTCNPTYNEMLVYDgIPKGDL 1570
Cdd:cd08406     2 GEILLSLSYlpTAERLTVVVVKARNLVWDNGKTTADPFVKVYLLQDGRKISKKKTSVKRDDTNPIFNEAMIFS-VPAIVL 80


                  ....*....
gi 157786960 1571 QQRELQLSV 1579
Cdd:cd08406    81 QDLSLRVTV 89
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 1495-1601 1.20e-10

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


Pssm-ID: 175976 [Multi-domain]  Cd Length: 133  Bit Score: 60.71  E-value: 1.20e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1495 VKLSISYKNNKLFIMVMHIRGLQPLQDGSDPDPYVKIYLLPDPQ--KATKRKTKVARKTCNPTYNEMLVYDgIPKGDLQQ 1572
Cdd:cd04009     7 VKAYYRASEQSLRVEILNARNLLPLDSNGSSDPFVKVELLPRHLfpDVPTPKTQVKKKTLFPLFDESFEFN-VPPEQCSV 85

                          90       100       110
                  ....*....|....*....|....*....|.
gi 157786960 1573 RE--LQLSVLSEQGFWENVLLGEVHIRLREL 1601
Cdd:cd04009    86 EGalLLFTVKDYDLLGSNDFEGEAFLPLNDI 116
C2B_RasGAP cd08675
C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 1506-1616 1.28e-10

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: 60.85  E-value: 1.28e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1506 LFIMVMHIRGLQPLQDGSDpDPYVKIYLLpDPQKATKRKTKVARKTCNPTYNEMLVYDGI------------PKGDLQQR 1573
Cdd:cd08675     1 LSVRVLECRDLALKSNGTC-DPFARVTLN-YSSKTDTKRTKVKKKTNNPRFDEAFYFELTigfsyekksfkvEEEDLEKS 78

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|...
gi 157786960 1574 ELQLSVLSEQGFWENVLLGEVHIRLRELDLAQEKTGWFALGSR 1616
Cdd:cd08675    79 ELRVELWHASMVSGDDFLGEVRIPLQGLQQAGSHQAWYFLQPR 121
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
 1062-1202 2.41e-10

Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large family of typical PKs that includes serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins, as well as pseudokinases that lack crucial residues for catalytic activity and/or ATP binding. It also includes phosphoinositide 3-kinases (PI3Ks), aminoglycoside 3'-phosphotransferases (APHs), choline kinase (ChoK), Actin-Fragmin Kinase (AFK), and the atypical RIO and Abc1p-like protein kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to their target substrates; these include serine/threonine/tyrosine residues in proteins for typical or atypical PKs, the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives for PI3Ks, the 4-hydroxyl of PtdIns for PI4Ks, and other small molecule substrates for APH/ChoK and similar proteins such as aminoglycosides, macrolides, choline, ethanolamine, and homoserine.


Pssm-ID: 270870 [Multi-domain]  Cd Length: 136  Bit Score: 60.15  E-value: 2.41e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1062 GENIRVIFKCGDD--------LRQDMLTLQMIRIMSKIwvqegldmrmvIFRCFSTGRGKG----MVEMIPNAETLRKIQ 1129
Cdd:cd13968    16 CTTIGVAVKIGDDvnneegedLESEMDILRRLKGLELN-----------IPKVLVTEDVDGpnilLMELVKGGTLIAYTQ 84

                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 157786960 1130 vehgvtgsfkdrpladwlqkhnpGEDEYEKAVENFIYSCAGCCVATYI--LGICDRHNDNIMLKTTGHMFHIDFG 1202
Cdd:cd13968    85 -----------------------EEELDEKDVESIMYQLAECMRLLHSfhLIHRDLNNDNILLSEDGNVKLIDFG 136
PX_p40phox cd06882
The phosphoinositide binding Phox Homology domain of the p40phox subunit of NADPH oxidase; The ...
 1363-1467 2.94e-10

The phosphoinositide binding Phox Homology domain of the p40phox subunit of NADPH oxidase; The PX domain is a phosphoinositide binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. p40phox contains an N-terminal PX domain, a central SH3 domain that binds p47phox, and a C-terminal PB1 domain that interacts with p67phox. It is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. The PX domain is a phospholipid-binding module involved in the membrane targeting of proteins. The p40phox PX domain binds to PI3P, an abundant lipid in phagosomal membranes, playing an important role in the localization of NADPH oxidase. The PX domain of p40phox is also involved in protein-protein interaction.


Pssm-ID: 132792  Cd Length: 123  Bit Score: 59.37  E-value: 2.94e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1363 EKVFHPSKGYIYVVKVMRENAhEATYIQRTFEEFQELHNKLRLLFP--------SSFLPSFPSRFVIGRSRgeAVAERRK 1434
Cdd:cd06882    12 EEKRGFTNYYVFVIEVKTKGG-SKYLIYRRYRQFFALQSKLEERFGpeagssayDCTLPTLPGKIYVGRKA--EIAERRI 88

                          90       100       110
                  ....*....|....*....|....*....|...
gi 157786960 1435 EELNGYIWHLIHAAPEVAECDLVYTFFHPLPRD 1467
Cdd:cd06882    89 PLLNRYMKELLSLPVWVLMDEDVRLFFYQTESD 121
PX_p47phox cd06887
The phosphoinositide binding Phox Homology domain of the p47phox subunit of NADPH oxidase; The ...
 1354-1465 3.06e-10

The phosphoinositide binding Phox Homology domain of the p47phox subunit of NADPH oxidase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. p47phox is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal PX domain, two Src Homology 3 (SH3) domains, and a C-terminal domain that contains PxxP motifs for binding SH3 domains. The PX domain of p47phox is unique in that it contains two distinct basic pockets on the membrane-binding surface: one preferentially binds phosphatidylinositol-3,4-bisphosphate [PI(3,4)P2] and is analogous to the PI3P-binding pocket of p40phox, while the other binds anionic phospholipids such as phosphatidic acid or phosphatidylserine. Simultaneous binding in the two pockets results in increased membrane affinity. The PX domain of p47phox is also involved in protein-protein interaction.


Pssm-ID: 132797  Cd Length: 118  Bit Score: 59.08  E-value: 3.06e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1354 IRDVFLCRHEKVFHPSKGYIYVVKVMRENAHEATyIQRTFEEFQELHNKLRLLFP---------SSFLPSFPSRFVIGrs 1424
Cdd:cd06887     1 IRHIALLGFEKRFVPSQHYVYMFLVKWQDLSEKL-VYRRFTEIYEFHKTLKEMFPieagdinkeNRIIPHLPAPKWFD-- 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 157786960 1425 rGEAVAERRKEELNGYIWHLIHAAPEVAECDLVYTFFHPLP 1465
Cdd:cd06887    78 -GQRAAENRQGTLTEYCSTLLSLPPKISRCPHVLDFFKVRP 117
PX_PI3K_C2_gamma cd06896
The phosphoinositide binding Phox Homology Domain of the Gamma Isoform of Class II ...
 1366-1461 5.93e-10

The phosphoinositide binding Phox Homology Domain of the Gamma Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II gamma isoform, PI3K-C2gamma, is expressed in the liver, breast, and prostate. It's biological function remains unknown. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


Pssm-ID: 132806  Cd Length: 101  Bit Score: 58.00  E-value: 5.93e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1366 FHPSKGYIYVVKVMRENaHEATYIQRTFEEFQELHNKLRLLFPSSFLPSFPSRFVIGRSRGEavaERRKEELNGYIWHLI 1445
Cdd:cd06896     7 FSKKSSNLYLVQVTQSC-NLVSLTEKSFEQFSELHSQLQKQFPSLALPEFPHWWHLPFTDSD---HKRVRDLNHYLEQLL 82

                          90
                  ....*....|....*.
gi 157786960 1446 HAAPEVAECDLVYTFF 1461
Cdd:cd06896    83 SGSREVANSDCVLSFF 98
C2_PI3K_class_I_alpha cd08398
C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 620-745 1.06e-09

C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. The members here are class I, alpha isoform PI3Ks and contain both a Ras-binding domain and a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. 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-I topology.


Pssm-ID: 176043  Cd Length: 158  Bit Score: 59.03  E-value: 1.06e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  620 FTVYGTHRIPIIWAT-----SYEEFYLSCSLSHGGKELCSPLQTRRAHFSKYLfhliiWDQQICFPVQVNRLPRETLLCA 694
Cdd:cd08398     4 WKINSNLRIKILCATyvnvnDIDKIYVRTGIYHGGEPLCDNVNTQRVPCSNPR-----WNEWLDYDIYIPDLPRSARLCL 78

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....
gi 157786960  695 TLYALpipppgssseaNKQKRVPE---ALGWVTTPLFNFRQVLTCGRKLLGLWP 745
Cdd:cd08398    79 SICSV-----------KGRKGAKEehcPLAWGNINLFDYTDTLVSGKMALNLWP 121
C2B_Synaptotagmin-13 cd08407
C2 domain second repeat present in Synaptotagmin 13; Synaptotagmin is a membrane-trafficking ...
 1493-1598 1.65e-09

C2 domain second repeat present in Synaptotagmin 13; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 13, a member of class 6 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmins 8 and 12, does not have any consensus Ca2+ binding sites. 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: 176052 [Multi-domain]  Cd Length: 138  Bit Score: 57.68  E-value: 1.65e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1493 GEVKLSISY--KNNKLFIMVMHIRGLQP--LQDGSDPDPYVKIYLLPDPQKATKRKTKVARKTCNPTYNEMLVYDgIPKG 1568
Cdd:cd08407     2 GEVLLSISYlpAANRLLVVVIKAKNLHSdqLKLLLGIDVSVKVTLKHQNAKLKKKQTKRAKHKINPVWNEMIMFE-LPSE 80

                          90       100       110
                  ....*....|....*....|....*....|
gi 157786960 1569 DLQQRELQLSVLSEQGFWENVLLGEVHIRL 1598
Cdd:cd08407    81 LLAASSVELEVLNQDSPGQSLPLGRCSLGL 110
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 1115-1202 1.82e-09

Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic domain, and a FATC (FRAP, ATM and TRRAP, C-terminal) domain at the C-terminus. It is also called FRAP (FK506 binding protein 12-rapamycin associated protein). TOR is a central component of the eukaryotic growth regulatory network. It controls the expression of many genes transcribed by all three RNA polymerases. It associates with other proteins to form two distinct complexes, TORC1 and TORC2. TORC1 is involved in diverse growth-related functions including protein synthesis, nutrient use and transport, autophagy and stress responses. TORC2 is involved in organizing cytoskeletal structures. TOR is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The TOR catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270713 [Multi-domain]  Cd Length: 279  Bit Score: 60.57  E-value: 1.82e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1115 MVEMIPNAETLRKIQ-VE---HGVTGSfKDRPLAD--WLQKHNPgedeyEKAVE---NFIYSCAGCCVATYILGICDRHN 1185
Cdd:cd05169   116 MLQMAPDYDNLTLIQkVEvfeYALENT-PGDDLRRvlWLKSPSS-----EAWLErrtNFTRSLAVMSMVGYILGLGDRHP 189

                          90
                  ....*....|....*...
gi 157786960 1186 DNIML-KTTGHMFHIDFG 1202
Cdd:cd05169   190 SNIMLdRLTGKVIHIDFG 207
C2B_RasA3 cd04010
C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of ...
 1526-1616 2.12e-09

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: 57.79  E-value: 2.12e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1526 DPYVKIYLLPDPQKATKRKTKVARKTCNPTYNEMLVYDG------------IPKGDLQQRELQLSVLSEQGFWENVLLGE 1593
Cdd:cd04010    20 DPYASVTLIYSNKKQDTKRTKVKKKTNNPQFDEAFYFDVtidsspekkqfeMPEEDAEKLELRVDLWHASMGGGDVFLGE 99

                          90       100
                  ....*....|....*....|....
gi 157786960 1594 VHIRLRELDLAQ-EKTGWFALGSR 1616
Cdd:cd04010   100 VRIPLRGLDLQAgSHQAWYFLQPR 123
C2B_Synaptotagmin-15 cd08409
C2 domain second repeat present in Synaptotagmin 15; Synaptotagmin is a membrane-trafficking ...
 1493-1594 1.23e-08

C2 domain second repeat present in Synaptotagmin 15; 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. 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: 176054 [Multi-domain]  Cd Length: 137  Bit Score: 55.03  E-value: 1.23e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1493 GEVKLSISYKN--NKLFIMVMHIRGLQPLqDGSDPDPYVKIYLLPDPQKATKRKTKVARKTCNPTYNEMLVYdGIPKGDL 1570
Cdd:cd08409     2 GDIQISLTYNPtlNRLTVVVLRARGLRQL-DHAHTSVYVKVSLMIHNKVVKTKKTEVVDGAASPSFNESFSF-KVTSRQL 79

                          90       100
                  ....*....|....*....|....
gi 157786960 1571 QQRELQLSVLSEQGFWENVLLGEV 1594
Cdd:cd08409    80 DTASLSLSVMQSGGVRKSKLLGRV 103
C2_PI3K_class_III cd08397
C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 638-759 1.77e-08

C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. These are the only domains identified in the class III PI3Ks present in this cd. In addition some PI3Ks contain a Ras-binding domain and/or a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. 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: 176042  Cd Length: 159  Bit Score: 55.33  E-value: 1.77e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  638 EFYLSCSLSHGGKELCSPLQTRRAHFSKylfhLIIWDQQICFPVQVNRLPRETLLCATLYAlpIPPPGssseankqKRVP 717
Cdd:cd08397    31 DLFVTCQVFDDGKPLTLPVQTSYKPFKN----RRNWNEWLTLPIKYSDLPRNSQLAITIWD--VSGTG--------KAVP 96

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|..
gi 157786960  718 eaLGWVTTPLFNFRQVLTCGRKLLGLWPATQENSSARWSAPN 759
Cdd:cd08397    97 --FGGTTLSLFNKDGTLRRGRQKLRVWPDVEADGSIPTSTGK 136
PX_UP2_fungi cd06869
The phosphoinositide binding Phox Homology domain of uncharacterized fungal proteins; The PX ...
 1372-1462 2.84e-08

The phosphoinositide binding Phox Homology domain of uncharacterized fungal proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized fungal proteins containing a PX domain. PX domain harboring proteins have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction.


Pssm-ID: 132779  Cd Length: 119  Bit Score: 53.44  E-value: 2.84e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1372 YIYVVKVMRENAHEAT-YIQRTFEEFQELHNKLRLLFPSSFLPSFPSRFVIGRsrgeavaERRKEELNGYIwHLIHAAPE 1450
Cdd:cd06869    34 YEFIIRVRREGEEYRTiYVARRYSDFKKLHHDLKKEFPGKKLPKLPHKDKLPR-------EKLRLSLRQYL-RSLLKDPE 105

                          90
                  ....*....|..
gi 157786960 1451 VAECDLVYTFFH 1462
Cdd:cd06869   106 VAHSSILQEFLT 117
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 645-746 3.51e-08

C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. The members here are class I, beta and delta isoforms of PI3Ks and contain both a Ras-binding domain and a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. 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-I topology.


Pssm-ID: 176075  Cd Length: 173  Bit Score: 54.63  E-value: 3.51e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  645 LSHGGKELCSPLQTRRAhfSKYLFHliIWDQQICFPVQVNRLPRETLLCATLYALPIPPPG-SSSEANKQKRVPEA---L 720
Cdd:cd08693    35 LFHGGESLCKTVKTSEV--SGKNDP--VWNETLEFDINVCDLPRMARLCFAIYEVSKKAKGkRSRKNQTKKKKKKDdnpI 110

                          90       100
                  ....*....|....*....|....*.
gi 157786960  721 GWVTTPLFNFRQVLTCGRKLLGLWPA 746
Cdd:cd08693   111 AWVNTMVFDYKGQLKTGDHTLYMWTY 136
C2B_Synaptotagmin-14_16 cd08408
C2 domain second repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are ...
 1494-1614 5.07e-07

C2 domain second repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are membrane-trafficking proteins in specific tissues outside the brain. Both of these contain C-terminal tandem C2 repeats, but only Synaptotagmin 14 has an N-terminal transmembrane domain and a putative fatty-acylation site. 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 and this is indeed the case here. 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: 176053 [Multi-domain]  Cd Length: 138  Bit Score: 50.44  E-value: 5.07e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1494 EVKLSISYK--NNKLFIMVMHIRGLQPLQDGSDPDPYVKIYLL-PDPQKATKRKTKVARKTCNPTYNEMLVYDgIPKGDL 1570
Cdd:cd08408     3 ELLLGLEYNalTGRLSVEVIKGSNFKNLAMNKAPDTYVKLTLLnSDGQEISKSKTSIRRGQPDPEFKETFVFQ-VALFQL 81

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 157786960 1571 QQRELQLSVLSEQGfwenvllgevhiRLREldlaqEKTGWFALG 1614
Cdd:cd08408    82 SEVTLMFSVYNKRK------------MKRK-----EMIGWFSLG 108
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
 1163-1202 2.03e-06

Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA double strand breaks (DSBs) caused by radiation. It is activated at the site of a DSB and phosphorylates key substrates that trigger pathways that regulate DNA repair and cell cycle checkpoints at the G1/S, S phase, and G2/M transition. Patients with the human genetic disorder Ataxia telangiectasia (A-T), caused by truncating mutations in ATM, show genome instability, increased cancer risk, immunodeficiency, compromised mobility, and neurodegeneration. A-T displays clinical heterogeneity, which is correlated to the degree of retained ATM activity. ATM contains a FAT (FRAP, ATM and TRRAP) domain, a catalytic domain, and a FATC domain at the C-terminus. It is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The ATM catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270715 [Multi-domain]  Cd Length: 282  Bit Score: 51.39  E-value: 2.03e-06
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|.
gi 157786960 1163 NFIYSCAGCCVATYILGICDRHNDNIML-KTTGHMFHIDFG 1202
Cdd:cd05171   171 AYTRSVATSSIVGYILGLGDRHLNNILIdQKTGELVHIDLG 211
C2A_Synaptotagmin-14_16 cd08389
C2A domain first repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are ...
 1491-1613 1.42e-05

C2A domain first repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are membrane-trafficking proteins in specific tissues outside the brain. Both of these contain C-terminal tandem C2 repeats, but only Synaptotagmin 14 has an N-terminal transmembrane domain and a putative fatty-acylation site. 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 and this is indeed the case here. 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: 176035 [Multi-domain]  Cd Length: 124  Bit Score: 46.08  E-value: 1.42e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1491 VGGEVKLSISYK--NNKLFIMVMHIRGLQPLQDGSDPDPYVKIYLLPdpQKATKRKTKVaRKTCNPTYNEMLVYDGIPKG 1568
Cdd:cd08389     1 KCGDLDVAFEYDpsARKLTVTVIRAQDIPTKDRGGASSWQVHLVLLP--SKKQRAKTKV-QRGPNPVFNETFTFSRVEPE 77

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 157786960 1569 DLQQRELQLSVLSEQGFWENVLLGEVHIRLRELDLAQEKTGWFAL 1613
Cdd:cd08389    78 ELNNMALRFRLYGVERMRKERLIGEKVVPLSQLNLEGETTVWLTL 122
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
 1139-1201 1.58e-05

Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical role in the mRNA surveillance mechanism known as non-sense mediated mRNA decay (NMD). NMD protects the cells from the accumulation of aberrant mRNAs with premature termination codons (PTCs) generated by genome mutations and by errors during transcription and splicing. SMG-1 phosphorylates Upf1, another central component of NMD, at the C-terminus upon recognition of PTCs. The phosphorylation/dephosphorylation cycle of Upf1 is essential for promoting NMD. In addition to its catalytic domain, SMG-1 contains a FATC (FRAP, ATM and TRRAP, C-terminal) domain at the C-terminus. SMG-1 is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The SMG-1 catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270714  Cd Length: 304  Bit Score: 48.79  E-value: 1.58e-05
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 157786960 1139 KDRPlADWLQK----HNPGEDEYEKAVENFIYSCAGCCVATYILGICDRHNDNIMLK-TTGHMFHIDF 1201
Cdd:cd05170   166 AETP-RDLLARelwcSSPSSAEWWRVTQRFARSLAVMSMIGYIIGLGDRHLDNILVDlSTGEVVHIDY 232
PX_SNX18 cd07286
The phosphoinositide binding Phox Homology domain of Sorting Nexin 18; The PX domain is a ...
 1383-1469 1.73e-05

The phosphoinositide binding Phox Homology domain of Sorting Nexin 18; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX18, like SNX9, contains an N-terminal Src Homology 3 (SH3) domain, a PX domain, and a C-terminal Bin/Amphiphysin/Rvs (BAR) domain, which detects membrane curvature. The PX-BAR structural unit helps determine specific membrane localization. SNX18 is localized to peripheral endosomal structures, and acts in a trafficking pathway that is clathrin-independent but relies on AP-1 and PACS1.


Pssm-ID: 132819  Cd Length: 127  Bit Score: 45.82  E-value: 1.73e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1383 AHEATYIQRTFEEFQELHNKLRLLFPSSFLPSFPSRFVIGRSRGEAVAERRKeelnGYIWHLIHAA--PEVAECDLVYTF 1460
Cdd:cd07286    28 SHTGLQVHRRYKHFDWLYARLAEKFPVISVPHIPEKQATGRFEEDFISKRRK----GLIWWMDHMCshPVLARCDAFQHF 103


                  ....*....
gi 157786960 1461 FHPLPRDEK 1469
Cdd:cd07286   104 LTCPSTDEK 112
C2_PI3K_class_I_gamma cd08399
C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 628-745 2.23e-05

C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. The members here are class I, gamma isoform PI3Ks and contain both a Ras-binding domain and a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. 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-I topology.


Pssm-ID: 176044  Cd Length: 178  Bit Score: 46.83  E-value: 2.23e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960  628 IPIIWATSYEEFYLSCSLSHGGKELCSplqtRRAHfSKYLFHLIIWDQQICFPVQVNRLPRETLLCATLYAlpIPPPGSS 707
Cdd:cd08399    21 IPVLPRNTDLTVFVEANIQHGQQVLCQ----RRTS-PKPFTEEVLWNTWLEFDIKIKDLPKGALLNLQIYC--GKAPALS 93

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 157786960  708 SEANKQKRVPEA------LGWVTTPLFNFRQVLTCGRKLLGLWP 745
Cdd:cd08399    94 SKKSAESPSSESkgkhqlLYYVNLLLIDHRFLLRTGEYVLHMWQ 137
C2B_Synaptotagmin-like cd04050
C2 domain second repeat present in Synaptotagmin-like proteins; Synaptotagmin is a ...
 1522-1618 2.61e-05

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


Pssm-ID: 176015 [Multi-domain]  Cd Length: 105  Bit Score: 44.86  E-value: 2.61e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1522 GSDPDPYVKIYLlpdpQKaTKRKTKVARKTCNPTYNE---MLVYDgiPKGDlqqrELQLSVLSEqgfWENVLLGEVHIRL 1598
Cdd:cd04050    18 TKEPSPYVELTV----GK-TTQKSKVKERTNNPVWEEgftFLVRN--PENQ----ELEIEVKDD---KTGKSLGSLTLPL 83

                          90       100
                  ....*....|....*....|..
gi 157786960 1599 RELDLAQEKT--GWFALGSRGH 1618
Cdd:cd04050    84 SELLKEPDLTldQPFPLDNSGP 105
PX_NoxO1 cd06889
The phosphoinositide binding Phox Homology domain of Nox Organizing protein 1; The PX domain ...
 1365-1463 4.88e-05

The phosphoinositide binding Phox Homology domain of Nox Organizing protein 1; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Nox Organizing protein 1 (NoxO1) is a critical regulator of enzyme kinetics of the nonphagocytic NADPH oxidase Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Nox1 is expressed in colon, stomach, uterus, prostate, and vascular smooth muscle cells. NoxO1, a homolog of the p47phox subunit of phagocytic NADPH oxidase, is involved in targeting activator subunits (such as NoxA1) to Nox1. It is co-localized with Nox1 in the membranes of resting cells and directs the subcellular localization of Nox1. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. The PX domain of NoxO1 preferentially binds phosphatidylinositol-3,5-bisphosphate [PI(3,5)P2], PI5P, and PI4P.


Pssm-ID: 132799  Cd Length: 121  Bit Score: 44.30  E-value: 4.88e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1365 VFHPSKGYIYVVKVMRENAHEaTYIQRTFEEFQELHNKLRLLFPSS---------FLPSFPSRFVIGRSRGEA--VAERR 1433
Cdd:cd06889    13 VMQKRRHKTYMFSVLWSDGSE-LFVYRSLEEFRKLHKQLKEKFPVEagllrssdrVLPKFKDAPSLGSLKGSTsrSLARL 91

                          90       100       110
                  ....*....|....*....|....*....|
gi 157786960 1434 KeELNGYIWHLIHAAPEVAECDLVYTFFHP 1463
Cdd:cd06889    92 K-LLETYCQELLRLDEKVSRSPEVIQFFAP 120
C2_E3_ubiquitin_ligase cd04021
C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation ...
 1525-1601 1.74e-04

C2 domain present in E3 ubiquitin ligase; E3 ubiquitin ligase is part of the ubiquitylation mechanism responsible for controlling surface expression of membrane proteins. The sequential action of several enzymes are involved: ubiquitin-activating enzyme E1, ubiquitin-conjugating enzyme E2, and ubiquitin-protein ligase E3 which is responsible for substrate recognition and promoting the transfer of ubiquitin to the target protein. E3 ubiquitin ligase is composed of an N-terminal C2 domain, 4 WW domains, and a HECTc domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175988 [Multi-domain]  Cd Length: 125  Bit Score: 43.03  E-value: 1.74e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 157786960 1525 PDPYVKIylLPDPQKAtkRKTKVARKTCNPTYNEMLVYDGIPkgdlqQRELQLSVLSEQGFWENVLLGEVHIRLREL 1601
Cdd:cd04021    22 PDPYVEV--TVDGQPP--KKTEVSKKTSNPKWNEHFTVLVTP-----QSTLEFKVWSHHTLKADVLLGEASLDLSDI 89
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1522-1593 3.61e-04

C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 175978 [Multi-domain]  Cd Length: 111  Bit Score: 41.79  E-value: 3.61e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 157786960 1522 GSDPDPYVKIYLLPDpqkatKRKTKVARKTCNPTYNEMLVYD-GIPKGDLQQRELQLSVLSEQGFWENVLLGE 1593
Cdd:cd04011    18 GGNIDPVVKVEVGGQ-----KKYTSVKKGTNCPFYNEYFFFNfHESPDELFDKIIKISVYDSRSLRSDTLIGS 85
PX_HS1BP3 cd06868
The phosphoinositide binding Phox Homology domain of HS1BP3; The PX domain is a ...
 1389-1460 3.94e-04

The phosphoinositide binding Phox Homology domain of HS1BP3; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Hematopoietic lineage cell-specific protein-1 (HS1) binding protein 3 (HS1BP3) associates with HS1 proteins through their SH3 domains, suggesting a role in mediating signaling. It has been reported that HS1BP3 might affect the IL-2 signaling pathway in hematopoietic lineage cells. Mutations in HS1BP3 may also be associated with familial Parkinson disease and essential tremor. HS1BP3 contains a PX domain, a leucine zipper, motifs similar to immunoreceptor tyrosine-based inhibitory motif and proline-rich regions. The PX domain interacts with PIs and plays a role in targeting proteins to PI-enriched membranes.


Pssm-ID: 132778  Cd Length: 120  Bit Score: 41.63  E-value: 3.94e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 157786960 1389 IQRTFEEFQELHNKLRLLFPSSFLPSFPSRFVIgrsRGEAVAERRKEELNGYIwHLIHAAPEVAECDLVYTF 1460
Cdd:cd06868    49 VSKKYSEFEELYKKLSEKYPGTILPPLPRKALF---VSESDIRERRAAFNDFM-RFISKDEKLANCPELLEF 116
C2B_Tricalbin-like cd04052
C2 domain second repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 1524-1619 4.14e-04

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


Pssm-ID: 176017 [Multi-domain]  Cd Length: 111  Bit Score: 41.43  E-value: 4.14e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1524 DPDPYVKIYLlpDPQKAtkRKTKVARKTCNPTYN---EMLVYDgipkgdlqQR--ELQLSVLSEQGFWENVlLGEVHIRL 1598
Cdd:cd04052    12 LLSPYAELYL--NGKLV--YTTRVKKKTNNPSWNastEFLVTD--------RRksRVTVVVKDDRDRHDPV-LGSVSISL 78

                          90       100
                  ....*....|....*....|..
gi 157786960 1599 REL-DLAQEKTGWFALGSRGHG 1619
Cdd:cd04052    79 NDLiDATSVGQQWFPLSGNGQG 100
PX_RUN cd07277
The phosphoinositide binding Phox Homology domain of uncharacterized proteins containing PX ...
 1389-1454 4.18e-04

The phosphoinositide binding Phox Homology domain of uncharacterized proteins containing PX and RUN domains; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized proteins containing an N-terminal RUN domain and a C-terminal PX domain. PX domain harboring proteins have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction. The RUN domain is found in GTPases in the Rap and Rab families and may play a role in Ras-like signaling pathways.


Pssm-ID: 132810  Cd Length: 118  Bit Score: 41.56  E-value: 4.18e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 157786960 1389 IQRTFEEFQELHNKLRLLFPS--SFlpSFPSRFVIGRSRGEAVAERRKeELNGYIW----HLIHAAPEVAEC 1454
Cdd:cd07277    34 VYRRYSEFYELHKKLKKKFPVvrSF--DFPPKKAIGNKDAKFVEERRK-RLQVYLRrvvnTLIQTSPELTAC 102
C2B_Synaptotagmin-17 cd08410
C2 domain second repeat present in Synaptotagmin 17; Synaptotagmin is a membrane-trafficking ...
 1493-1579 5.59e-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: 41.80  E-value: 5.59e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1493 GEVKLSISYKNNKLFIMVMHIRGLQPLQ----DGSDPdpYVKIYLLPDPQKATKRKTKVARKTCNPTYNEMLVYDgIPKG 1568
Cdd:cd08410     1 GELLLSLNYLPSAGRLNVDIIRAKQLLQtdmsQGSDP--FVKIQLVHGLKLIKTKKTSCMRGTIDPFYNESFSFK-VPQE 77

                          90
                  ....*....|.
gi 157786960 1569 DLQQRELQLSV 1579
Cdd:cd08410    78 ELENVSLVFTV 88
PX_Bem1p cd06890
The phosphoinositide binding Phox Homology domain of Bem1p; The PX domain is a ...
 1363-1464 7.48e-04

The phosphoinositide binding Phox Homology domain of Bem1p; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Members of this subfamily bear similarity to Saccharomyces cerevisiae Bem1p, containing two Src Homology 3 (SH3) domains at the N-terminus, a central PX domain, and a C-terminal PB1 domain. Bem1p is a scaffolding protein that is critical for proper Cdc42p activation during bud formation in yeast. During budding and mating, Bem1p migrates to the plasma membrane where it can serve as an adaptor for Cdc42p and some other proteins. Bem1p also functions as an effector of the G1 cyclin Cln3p and the cyclin-dependent kinase Cdc28p in promoting vacuolar fusion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. The PX domain of Bem1p specifically binds phosphatidylinositol-4-phosphate (PI4P).


Pssm-ID: 132800  Cd Length: 112  Bit Score: 40.73  E-value: 7.48e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1363 EKVFHPSKGYIYVVKVMRENAHEaTYIQRTFEEFQELHNKLRLLFPSSFLPSFPSRfVIGRSRG-------EAVAERRKE 1435
Cdd:cd06890     6 ESVLLEDNRYWYRVRATLSDGKT-RYLCRYYQDFYKLHIALLDLFPAEAGRNSSKR-ILPYLPGpvtdvvnDSISLKRLN 83

                          90       100
                  ....*....|....*....|....*....
gi 157786960 1436 ELNGYIWHLIHAAPEVAECDLVYTFFHPL 1464
Cdd:cd06890    84 DLNEYLNELINLPAYIQTSEVVRDFFANR 112
C2B_RasA1_RasA4 cd04025
C2 domain second repeat present in RasA1 and RasA4; RasA1 and RasA4 are GAP1s (GTPase ...
 1505-1614 9.12e-04

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


Pssm-ID: 175991 [Multi-domain]  Cd Length: 123  Bit Score: 40.93  E-value: 9.12e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1505 KLFIMVMHIRGLQPLQDGSDPDPYVKIYLlpdpqKATKRKTKVARKTCNPTYNEMLvydgipkgDLQQRELQLSVLS-EQ 1583
Cdd:cd04025     1 RLRCHVLEARDLAPKDRNGTSDPFVRVFY-----NGQTLETSVVKKSCYPRWNEVF--------EFELMEGADSPLSvEV 67

                          90       100       110
                  ....*....|....*....|....*....|....*
gi 157786960 1584 GFWE----NVLLGEVHIRLRELDLAQEKTGWFALG 1614
Cdd:cd04025    68 WDWDlvskNDFLGKVVFSIQTLQQAKQEEGWFRLL 102
C2_SRC2_like cd04051
C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production ...
 1508-1601 9.99e-04

C2 domain present in Soybean genes Regulated by Cold 2 (SRC2)-like proteins; SRC2 production is a response to pathogen infiltration. The initial response of increased Ca2+ concentrations are coupled to downstream signal transduction pathways via calcium binding proteins. SRC2 contains a single C2 domain which localizes to the plasma membrane and is involved in Ca2+ dependent protein binding. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176016 [Multi-domain]  Cd Length: 125  Bit Score: 40.68  E-value: 9.99e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1508 IMVMHIRGLQPLQDGSDPDPYVKIYLLPDpqkaTKRKTKVARKT-CNPTYNEMLVYDgIPKGDLQQRELQLSV--LSEQG 1584
Cdd:cd04051     4 ITIISAEDLKNVNLFGKMKVYAVVWIDPS----HKQSTPVDRDGgTNPTWNETLRFP-LDERLLQQGRLALTIevYCERP 78

                          90
                  ....*....|....*..
gi 157786960 1585 FWENVLLGEVHIRLREL 1601
Cdd:cd04051    79 SLGDKLIGEVRVPLKDL 95
PX_SNX19_like_plant cd06872
The phosphoinositide binding Phox Homology domain of uncharacterized SNX19-like plant proteins; ...
 1369-1460 1.04e-03

The phosphoinositide binding Phox Homology domain of uncharacterized SNX19-like plant proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized plant proteins containing an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some sorting nexins (SNXs). This is the same domain architecture found in SNX19. SNX13 and SNX14 also contain these three domains but also contain a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction.


Pssm-ID: 132782  Cd Length: 107  Bit Score: 40.20  E-value: 1.04e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1369 SKGY-IYVVKVmRENAHEATYIQRTFEEFQELHNKLRlLFPSSFLpSFPSRFVIGRSRGEAVAERRKEELNGYIwHLIHA 1447
Cdd:cd06872    15 SKSFaVYSVAV-TDNENETWVVKRRFRNFETLHRRLK-EVPKYNL-ELPPKRFLSSSLDGAFIEERCKLLDKYL-KDLLV 90

                          90
                  ....*....|...
gi 157786960 1448 APEVAECDLVYTF 1460
Cdd:cd06872    91 IEKVAESHEVWSF 103
C2_Rab11-FIP_classI cd08682
C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit ...
 1510-1616 1.17e-03

C2 domain found in Rab11-family interacting proteins (FIP) class I; Rab GTPases recruit various effector proteins to organelles and vesicles. Rab11-family interacting proteins (FIPs) are involved in mediating the role of Rab11. FIPs can be divided into three classes: class I FIPs (Rip11a, Rip11b, RCP, and FIP2) which contain a C2 domain after N-terminus of the protein, class II FIPs (FIP3 and FIP4) which contain two EF-hands and a proline rich region, and class III FIPs (FIP1) which exhibits no homology to known protein domains. All FIP proteins contain a highly conserved, 20-amino acid motif at the C-terminus of the protein, known as Rab11/25 binding domain (RBD). Class I FIPs are thought to bind to endocytic membranes via their C2 domain, which interacts directly with phospholipids. Class II FIPs do not have any membrane binding domains leaving much to speculate about the mechanism involving FIP3 and FIP4 interactions with endocytic membranes. The members in this CD are class I FIPs. The exact function of the Rab11 and FIP interaction is unknown, but there is speculation that it involves the role of forming a targeting complex that recruits a group of proteins involved in membrane transport to organelles. 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: 176064 [Multi-domain]  Cd Length: 126  Bit Score: 40.51  E-value: 1.17e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1510 VMHIRGLQPLQDGSDPDPYVKIYLLPDpqkatKRKTKVARKTCNPTYNEMLVYD--GIPKGDLQQRELQLSVLSEQGFWE 1587
Cdd:cd08682     5 VLQARGLLCKGKSGTNDAYVIIQLGKE-----KYSTSVKEKTTSPVWKEECSFElpGLLSGNGNRATLQLTVMHRNLLGL 79

                          90       100       110
                  ....*....|....*....|....*....|.
gi 157786960 1588 NVLLGEVHIRLRELDLAQ--EKTGWFALGSR 1616
Cdd:cd08682    80 DKFLGQVSIPLNDLDEDKgrRRTRWFKLESK 110
C2A_C2C_Synaptotagmin_like cd08391
C2 domain first and third repeat in Synaptotagmin-like proteins; Synaptotagmin is a ...
 1526-1621 1.17e-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: 40.35  E-value: 1.17e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1526 DPYVKIYLlpdpqKATKRKTKVARKTCNPTYNEmlVYDGIPKgDLQQRELQLSVLSEQG----FwenvlLGEVHIRLREL 1601
Cdd:cd08391    29 DPYVIVRV-----GAQTFKSKVIKENLNPKWNE--VYEAVVD-EVPGQELEIELFDEDPdkddF-----LGRLSIDLGSV 95

                          90       100
                  ....*....|....*....|
gi 157786960 1602 DLAQEKTGWFALGSRGHGTL 1621
Cdd:cd08391    96 EKKGFIDEWLPLEDVKSGRL 115
C2B_MCTP_PRT cd08376
C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 1508-1621 1.39e-03

C2 domain second repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); MCTPs are involved in Ca2+ signaling at the membrane. MCTP is composed of a variable N-terminal sequence, three 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 second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 176022 [Multi-domain]  Cd Length: 116  Bit Score: 39.93  E-value: 1.39e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1508 IMVMHIRGLQPLQDGSDPDPYVKIYLlpdpqKATKRKTKVARKTCNPTYNE---MLVYDGipkgdlQQRELQLSVLSEQG 1584
Cdd:cd08376     4 IVLVEGKNLPPMDDNGLSDPYVKFRL-----GNEKYKSKVCSKTLNPQWLEqfdLHLFDD------QSQILEIEVWDKDT 72

                          90       100       110
                  ....*....|....*....|....*....|....*..
gi 157786960 1585 FWENVLLGEVHIRLRELDLAQEKTGWFALGSrGHGTL 1621
Cdd:cd08376    73 GKKDEFIGRCEIDLSALPREQTHSLELELED-GEGSL 108
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 1526-1602 1.42e-03

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


Pssm-ID: 176005 [Multi-domain]  Cd Length: 115  Bit Score: 39.86  E-value: 1.42e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1526 DPYVKIYLlpDPQKATKrkTKVARKTCNPTYNEMLVydgIPKGDLQQRELQLSVLSeqgfW----ENVLLGEVHIRLREL 1601
Cdd:cd04040    21 DPFVKFYL--NGEKVFK--TKTIKKTLNPVWNESFE---VPVPSRVRAVLKVEVYD----WdrggKDDLLGSAYIDLSDL 89


                  .
gi 157786960 1602 D 1602
Cdd:cd04040    90 E 90
C2_Kibra cd08680
C2 domain found in Human protein Kibra; Kibra is thought to be a regulator of the Salvador ...
 1495-1613 1.73e-03

C2 domain found in Human protein Kibra; Kibra is thought to be a regulator of the Salvador (Sav)/Warts (Wts)/Hippo (Hpo) (SWH) signaling network, which limits tissue growth by inhibiting cell proliferation and promoting apoptosis. The core of the pathway consists of a MST and LATS family kinase cascade that ultimately phosphorylates and inactivates the YAP/Yorkie (Yki) transcription coactivator. The FERM domain proteins Merlin (Mer) and Expanded (Ex) are part of the upstream regulation controlling pathway mechanism. Kibra colocalizes and associates with Mer and Ex and is thought to transduce an extracellular signal via the SWH network. The apical scaffold machinery that contains Hpo, Wts, and Ex recruits Yki to the apical membrane facilitating its inhibitory phosphorlyation by Wts. Since Kibra associates with Ex and is apically located it is hypothesized that KIBRA is part of the scaffold, helps in the Hpo/Wts complex, and helps recruit Yki for inactivation that promotes SWH pathway activity. Kibra contains two amino-terminal WW domains, an internal C2-like domain, and a carboxy-terminal glutamic acid-rich stretch. 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: 176062  Cd Length: 124  Bit Score: 39.91  E-value: 1.73e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1495 VKLSISY--KNNKLFIMVMHIRGLQPL--QDGSDPdpYVKIYLLP-DPQKATKRKTKVARKTCNPTYNEMLVYDgIPKGD 1569
Cdd:cd08680     3 VQIGLRYdsGDSSLVISVEQLRNLSALsiPENSKV--YVRVALLPcSSSTSCLFRTKALEDQDKPVFNEVFRVP-ISSTK 79

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 157786960 1570 LQQRELQLSV--LSEQGFWEnvLLGEVHIRLRELDLAQEK-TGWFAL 1613
Cdd:cd08680    80 LYQKTLQVDVcsVGPDQQEE--CLGGAQISLADFESSEEMsTKWYNL 124
PX_KIF16B_SNX23 cd06874
The phosphoinositide binding Phox Homology domain of KIF16B kinesin or Sorting Nexin 23; The ...
 1389-1456 2.06e-03

The phosphoinositide binding Phox Homology domain of KIF16B kinesin or Sorting Nexin 23; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. KIF16B, also called sorting nexin 23 (SNX23), is a family-3 kinesin which harbors an N-terminal kinesin motor domain containing ATP and microtubule binding sites, a ForkHead Associated (FHA) domain, and a C-terminal PX domain. The PX domain of KIF16B binds to phosphatidylinositol-3-phosphate (PI3P) in early endosomes and plays a role in the transport of early endosomes to the plus end of microtubules. By regulating early endosome plus end motility, KIF16B modulates the balance between recycling and degradation of receptors. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.


Pssm-ID: 132784  Cd Length: 127  Bit Score: 40.06  E-value: 2.06e-03
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 157786960 1389 IQRTFEEFQELHNKLRLLFPSSFLPSFPSRFVIGrSRGEAVAERRKEELNGYIWHLIHAAPEVAECDL 1456
Cdd:cd06874    34 VFRRYSRFRELHKTMKLKYPEVAALEFPPKKLFG-NKSERVAKERRRQLETYLRNFFSVCLKLPACPL 100
C2_KIAA0528-like cd08688
C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the ...
 1526-1611 2.16e-03

C2 domain found in the Human KIAA0528 cDNA clone; The members of this CD are named after the Human KIAA0528 cDNA clone. All members here contain a single C2 repeat. No other information on this protein is currently known. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176070 [Multi-domain]  Cd Length: 110  Bit Score: 39.21  E-value: 2.16e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1526 DPYVKIYLLPDPQKatkrkTKVARKTCNPTYN-EMLVYDgIPKGDLQQRELQLSVLSEQGFWENVLLGEVHIRLREL--- 1601
Cdd:cd08688    22 DAFVEVKFGSTTYK-----TDVVKKSLNPVWNsEWFRFE-VDDEELQDEPLQIRVMDHDTYSANDAIGKVYIDLNPLllk 95

                          90
                  ....*....|
gi 157786960 1602 DLAQEKTGWF 1611
Cdd:cd08688    96 DSVSQISGWF 105
C2A_RasGAP cd08383
C2 domain (first repeat) of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 1525-1615 2.57e-03

C2 domain (first 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 either a single C2 domain or 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: 176029 [Multi-domain]  Cd Length: 117  Bit Score: 39.17  E-value: 2.57e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1525 PDPYVKIYLlpDPQKATKRKTKVARktcNPTYNEMLVYDgIPKGDLQQRELQLSVLSEQGFWENVLLGEVHirLRELDLA 1604
Cdd:cd08383    18 RDPYCTVSL--DQVEVARTKTVEKL---NPFWGEEFVFD-DPPPDVTFFTLSFYNKDKRSKDRDIVIGKVA--LSKLDLG 89

                          90
                  ....*....|.
gi 157786960 1605 QEKTGWFALGS 1615
Cdd:cd08383    90 QGKDEWFPLTP 100
PX_MONaKA cd06871
The phosphoinositide binding Phox Homology domain of Modulator of Na,K-ATPase; The PX domain ...
 1374-1463 3.38e-03

The phosphoinositide binding Phox Homology domain of Modulator of Na,K-ATPase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. MONaKA (Modulator of Na,K-ATPase) binds the plasma membrane ion transporter, Na,K-ATPase, and modulates its enzymatic and ion pump activities. It modulates brain Na,K-ATPase and may be involved in regulating electrical excitability and synaptic transmission. MONaKA contains an N-terminal PX domain and a C-terminal catalytic kinase domain. The PX domain interacts with PIs and plays a role in targeting proteins to PI-enriched membranes.


Pssm-ID: 132781  Cd Length: 120  Bit Score: 39.27  E-value: 3.38e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1374 YVVKVMRENAHEATY-IQRTFEEFQELHNKLRLlfpSSFLPSFPSRFVIGRSRGEAVAERRKeELNGYiWHLIHAAPEVA 1452
Cdd:cd06871    24 YIIRVQRGPSPENSWqVIRRYNDFDLLNASLQI---SGISLPLPPKKLIGNMDREFIAERQQ-GLQNY-LNVILMNPILA 98

                          90
                  ....*....|.
gi 157786960 1453 ECDLVYTFFHP 1463
Cdd:cd06871    99 SCLPVKKFLDP 109
PX_MDM1p cd06876
The phosphoinositide binding Phox Homology domain of yeast MDM1p; The PX domain is a ...
 1374-1460 4.64e-03

The phosphoinositide binding Phox Homology domain of yeast MDM1p; The PX domain is a phosphoinositide binding (PI) module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Yeast MDM1p is a filament-like protein localized in punctate structures distributed throughout the cytoplasm. It plays an important role in nuclear and mitochondrial transmission to daughter buds. Members of this subfamily show similar domain architectures as some sorting nexins (SNXs). Some members are similar to SNX19 in that they contain an N-terminal PXA domain, a central PX domain, and a C-terminal domain that is conserved in some SNXs. Others are similar to SNX13 and SNX14, which also harbor these three domains as well as a regulator of G protein signaling (RGS) domain in between the PXA and PX domains. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.


Pssm-ID: 132786  Cd Length: 133  Bit Score: 38.83  E-value: 4.64e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1374 YVVKVMR-ENAHEAT--YIQRTFEEFQELHNKLRLLFPSSFLPSFPSRFVIGRSRGEA-VAERRKEELNGYIWHLIhAAP 1449
Cdd:cd06876    41 YLIEVQRlNNDDQSSgwVVARRYSEFLELHKYLKKRYPGVLKLDFPQKRKISLKYSKTlLVEERRKALEKYLQELL-KIP 119

                          90
                  ....*....|.
gi 157786960 1450 EVAECDLVYTF 1460
Cdd:cd06876   120 EVCEDEEFRKF 130
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 1505-1596 5.09e-03

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-II topology.


Pssm-ID: 175989 [Multi-domain]  Cd Length: 127  Bit Score: 38.86  E-value: 5.09e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 157786960 1505 KLFIMVMHIRGLQPlQDGSDP-DPYVKIYLlpDPQKatkRKTKVARKTCNPTYNEMLVYDGIPKGDLQQRELQLSVLSEQ 1583
Cdd:cd04022     1 KLVVEVVDAQDLMP-KDGQGSsSAYVELDF--DGQK---KRTRTKPKDLNPVWNEKLVFNVSDPSRLSNLVLEVYVYNDR 74

                          90
                  ....*....|....
gi 157786960 1584 GFWE-NVLLGEVHI 1596
Cdd:cd04022    75 RSGRrRSFLGRVRI 88
C2D_Ferlin cd04017
C2 domain fourth repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1514-1565 8.53e-03

C2 domain fourth 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 fourth C2 repeat, C2D, and has a type-II topology.


Pssm-ID: 175984 [Multi-domain]  Cd Length: 135  Bit Score: 38.29  E-value: 8.53e-03
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|..
gi 157786960 1514 RGLQPLQDGSDPDPYVKIYLLPDPQKatkrkTKVARKTCNPTYNEMLVYDGI 1565
Cdd:cd04017    11 RDLLAADKSGLSDPFARVSFLNQSQE-----TEVIKETLSPTWDQTLIFDEV 57
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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