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Conserved domains on  [gi|1573060031|gb|RZC43219|]
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phosphatidylinositol 3-kinase catalytic subunit type 3 [Asbolus verrucosus]

Protein Classification

phosphatidylinositol 3-kinase( domain architecture ID 10170542)

phosphatidylinositol 3-kinase catalyzes 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

CATH:  1.10.510.10
EC:  2.7.1.137
Gene Ontology:  GO:0052742|GO:0016310|GO:0005524|GO:0046854|GO:0035032
PubMed:  16244704|17371248|9255069

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 584-927 0e+00

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: 582.57  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 584 LSQQQKFIDNLVKLVKSVLRESGNRKKKAEKLQQLLFDPtaFKFNFSNFEPIPFPLDPDIIIKGIIPEKASLFKSALMPS 663
Cdd:cd00896     4 LKRQQEFVDRLRSLMKEVKNEKGSRDKKIERLRELLSDS--ELGLLLFFEPLPLPLDPSVKVTGIIPEKSTVFKSALMPL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 664 KLHFITADNSEYVAIFKHGDDLRQDQLILQMITLMDKLLRKENLDLKLTPYKVLATSTRHGFVQFID-SVSVAEAVAAEG 742
Cdd:cd00896    82 KLTFKTLDGGEYKVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVPnSKALADILKKYG 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 743 SIHNYFRKYHPQENGPYGIAPDIMDSYVRSCAGYCVITYLLGVGDRHLDNLLLTTCGKLFHIDFGYILGRDPKPLPPPMK 822
Cdd:cd00896   162 SILNFLRKHNPDESGPYGIKPEVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHIDFGYILGRDPKPFPPPMK 241

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 823 LSKEMVEAMGGVNSEHYQEFRKQCYTAFLHLRRHANLMLNLFSLMIDASVPDIALEPDKAVRKVQDKFRLDLGEEEAVHY 902
Cdd:cd00896   242 LCKEMVEAMGGANSEGYKEFKKYCCTAYNILRKHANLILNLFSLMVDANIPDIALEPDKAVLKVQEKFRLDLSDEEAEQY 321

                         330       340
                  ....*....|....*....|....*
gi 1573060031 903 IQYLIDSSVTAVMPAIVEQFHKITQ 927
Cdd:cd00896   322 FQNLIDESVNALFPAVVETIHKIAQ 346
C2_PI3K_class_III cd08397
C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 27-186 3.31e-71

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: 232.14  E-value: 3.31e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  27 LEGKRQKPEYDKLLADPILKYSGLCQDGCSDLMVVCQIFDQNQPLALPVSTSYKAFTSRWSWNEWLTLPIQFNDLPRTAQ 106
Cdd:cd08397     1 LEGKVPLLSLSEKLEDPVLRFSGSNVSPNSDLFVTCQVFDDGKPLTLPVQTSYKPFKNRRNWNEWLTLPIKYSDLPRNSQ 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 107 LALTIYDCIGPNKLWPVGGTTISLFSKHGLFRQGMVDLRVFPNREADGNFPTeTPGKAKDQGKEQMQRLTKLTKKHRNGH 186
Cdd:cd08397    81 LAITIWDVSGTGKAVPFGGTTLSLFNKDGTLRRGRQKLRVWPDVEADGSIPT-STGKSPDSERDELDRLEKLLKKYERGE 159
PI3Ka_III cd00870
Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is ...
 283-544 4.03e-71

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: 232.22  E-value: 4.03e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 283 DKEAKPNATIRDILNTIVSYPSTKPLSNEEQDHVWKFRFYLSTQKKALAKFLKCVNWTQQNEVRQALSMMRIWVPMDVED 362
Cdd:cd00870     1 DKDLKPNSKERKELNKILKYPPTTKLTDEEKDLIWKFRFYLTNNKKALTKFLKSVNWSDEQEVKQALELMPKWAKIDIED 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 363 ALELLSPNFTHPAVRKYAISRLQQAPDEDILLYLLQLVQALKYENFKNIQEGYARvspgrdniivheekeaqlekkdske 442
Cdd:cd00870    81 ALELLSPYFTNPVVRKYAVSRLKLASDEELLLYLLQLVQALKYENLDLSPLPRLD------------------------- 135

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 443 snstitnesvmhrsssynqadqiassnansvievdvdprpaslpenilqnvytdsantdtlqdhmneeeevQDLATFLIQ 522
Cdd:cd00870   136 -----------------------------------------------------------------------SPLADFLIE 144

                         250       260
                  ....*....|....*....|..
gi 1573060031 523 RSCKNAKLANYFYWYLLIECED 544
Cdd:cd00870   145 RALKNPKLANFLYWYLKVELED 166
 
Name Accession Description Interval E-value
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 584-927 0e+00

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: 582.57  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 584 LSQQQKFIDNLVKLVKSVLRESGNRKKKAEKLQQLLFDPtaFKFNFSNFEPIPFPLDPDIIIKGIIPEKASLFKSALMPS 663
Cdd:cd00896     4 LKRQQEFVDRLRSLMKEVKNEKGSRDKKIERLRELLSDS--ELGLLLFFEPLPLPLDPSVKVTGIIPEKSTVFKSALMPL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 664 KLHFITADNSEYVAIFKHGDDLRQDQLILQMITLMDKLLRKENLDLKLTPYKVLATSTRHGFVQFID-SVSVAEAVAAEG 742
Cdd:cd00896    82 KLTFKTLDGGEYKVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVPnSKALADILKKYG 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 743 SIHNYFRKYHPQENGPYGIAPDIMDSYVRSCAGYCVITYLLGVGDRHLDNLLLTTCGKLFHIDFGYILGRDPKPLPPPMK 822
Cdd:cd00896   162 SILNFLRKHNPDESGPYGIKPEVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHIDFGYILGRDPKPFPPPMK 241

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 823 LSKEMVEAMGGVNSEHYQEFRKQCYTAFLHLRRHANLMLNLFSLMIDASVPDIALEPDKAVRKVQDKFRLDLGEEEAVHY 902
Cdd:cd00896   242 LCKEMVEAMGGANSEGYKEFKKYCCTAYNILRKHANLILNLFSLMVDANIPDIALEPDKAVLKVQEKFRLDLSDEEAEQY 321

                         330       340
                  ....*....|....*....|....*
gi 1573060031 903 IQYLIDSSVTAVMPAIVEQFHKITQ 927
Cdd:cd00896   322 FQNLIDESVNALFPAVVETIHKIAQ 346
C2_PI3K_class_III cd08397
C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 27-186 3.31e-71

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: 232.14  E-value: 3.31e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  27 LEGKRQKPEYDKLLADPILKYSGLCQDGCSDLMVVCQIFDQNQPLALPVSTSYKAFTSRWSWNEWLTLPIQFNDLPRTAQ 106
Cdd:cd08397     1 LEGKVPLLSLSEKLEDPVLRFSGSNVSPNSDLFVTCQVFDDGKPLTLPVQTSYKPFKNRRNWNEWLTLPIKYSDLPRNSQ 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 107 LALTIYDCIGPNKLWPVGGTTISLFSKHGLFRQGMVDLRVFPNREADGNFPTeTPGKAKDQGKEQMQRLTKLTKKHRNGH 186
Cdd:cd08397    81 LAITIWDVSGTGKAVPFGGTTLSLFNKDGTLRRGRQKLRVWPDVEADGSIPT-STGKSPDSERDELDRLEKLLKKYERGE 159
PI3Ka_III cd00870
Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is ...
 283-544 4.03e-71

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: 232.22  E-value: 4.03e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 283 DKEAKPNATIRDILNTIVSYPSTKPLSNEEQDHVWKFRFYLSTQKKALAKFLKCVNWTQQNEVRQALSMMRIWVPMDVED 362
Cdd:cd00870     1 DKDLKPNSKERKELNKILKYPPTTKLTDEEKDLIWKFRFYLTNNKKALTKFLKSVNWSDEQEVKQALELMPKWAKIDIED 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 363 ALELLSPNFTHPAVRKYAISRLQQAPDEDILLYLLQLVQALKYENFKNIQEGYARvspgrdniivheekeaqlekkdske 442
Cdd:cd00870    81 ALELLSPYFTNPVVRKYAVSRLKLASDEELLLYLLQLVQALKYENLDLSPLPRLD------------------------- 135

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 443 snstitnesvmhrsssynqadqiassnansvievdvdprpaslpenilqnvytdsantdtlqdhmneeeevQDLATFLIQ 522
Cdd:cd00870   136 -----------------------------------------------------------------------SPLADFLIE 144

                         250       260
                  ....*....|....*....|..
gi 1573060031 523 RSCKNAKLANYFYWYLLIECED 544
Cdd:cd00870   145 RALKNPKLANFLYWYLKVELED 166
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 678-879 2.29e-62

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: 211.00  E-value: 2.29e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  678 IFKHGDDLRQDQLILQMITLMDKLLRKE----NLDLKLTPYKVLATSTRHGFVQFI-DSVSVAE---------------- 736
Cdd:smart00146   2 IFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVpNSTTLHEilkeyrkqkgkvldlr 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  737 -----------------AVAAEGSIHNYFRKYHPQENGPYgiaPDIMDSYVRSCAGYCVITYLLGVGDRHLDNLLLTTCG 799
Cdd:smart00146  82 sqtatrlkklelfleatGKFPDPVLYDWFTKKFPDPSEDY---FEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTG 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  800 KLFHIDFGYILGRDPKPLPPPMKL----SKEMVEAMGgvNSEHYQEFRKQCYTAFLHLRRHANLMLNLFSLMIDASVPDI 875
Cdd:smart00146 159 HLFHIDFGFILGNGPKLFGFPERVpfrlTPEMVDVMG--DSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLPDW 236


                   ....
gi 1573060031  876 ALEP 879
Cdd:smart00146 237 RSGK 240
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 674-875 1.06e-56

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: 195.63  E-value: 1.06e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 674 EYVAIFKHGDDLRQDQLILQMITLMDKLLRKENLDLK-LTPYKVLATSTRHGFVQFIDSVSVA----------------- 735
Cdd:pfam00454   1 GYGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLRrLKPYSVIPLGPKCGIIEWVPNSETLayildeygengvpptam 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 736 --------------------EAVAAEGSIHNYFRKYHPQENGPYgiapDIMDSYVRSCAGYCVITYLLGVGDRHLDNLLL 795
Cdd:pfam00454  81 vkilhsalnypklklefesrISLPPKVGLLQWFVKKSPDAEEWG----EARKNFVRSCAGYSVLDYILGNGDRHLDNILV 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 796 -TTCGKLFHIDFGYILGRDPKPLPPPMKL----SKEMVEAMGgvNSEHYQEFRKQCYTAFLHLRRHANLMLNLFSLMIDA 870
Cdd:pfam00454 157 dKTTGKLFHIDFGLCLPDAGKDLPFPEKVpfrlTREMVYAMG--PSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVAD 234


                  ....*
gi 1573060031 871 SVPDI 875
Cdd:pfam00454 235 GLPDW 239
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 289-572 2.56e-56

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: 192.09  E-value: 2.56e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  289 NATIRDILNTIVSYPSTKPLSNEEQDHVWKFRFYLSTQ-KKALAKFLKCVNWTQQNEVRQALSMMRIWVPMDVEDALELL 367
Cdd:smart00145   4 DIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTNnPKALPKFLLSVKWSDADEVAQALSLLLSWAPLDPEDALELL 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  368 SPNFTHPAVRKYAISRLQQAPDEDILLYLLQLVQALKYENFKNiqegyarvspgrdniivheekeaqlekkdskesnsti 447
Cdd:smart00145  84 DPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLD------------------------------------- 126

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  448 tnesvmhrsssynqadqiassnansvievdvdprpaslpenilqnvytdsantdtlqdhmneeeevQDLATFLIQRSCKN 527
Cdd:smart00145 127 ------------------------------------------------------------------SALARFLLERALAN 140

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*.
gi 1573060031  528 AKLANYFYWYLLIECEDPEptMKQNI-LIRELYLTVMKTFSQTLAK 572
Cdd:smart00145 141 QRLGHFFYWYLKSELHDPH--VSIRFgLLLEAYLRGCGTHLKELLK 184
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
516-930 2.55e-51

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 196.93  E-value: 2.55e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  516 LATFLIQRSCKNAKLANYF--YWYLLIECEdpeptmkqNILIRELYLTVMKTFSQTLAKGSPEMQKKRLNLsqQQKFIDN 593
Cdd:COG5032   1643 LAQLLSRLSSENNKISVALliDKPLHEERE--------NFPSGLSLSSFQSSFLKELIKKSPRKIRKKFKI--DISLLNL 1712

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  594 LVKLVKSVLRESGNRKKKAEKLQQLLFDPTAFKF--NFSNFEPIPFPLDPDIIIKGIIPEKASLFKSALM-PSKLHFITA 670
Cdd:COG5032   1713 SRKLYISVLRSIRKRLKRLLELRLKKVSPKLLLFhaFLEIKLPGQYLLDKPFVLIERFEPEVSVVKSHLQrPRRLTIRGS 1792

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  671 DNSEYVAIFKHGDDLRQDQLILQMITLMDKLLRKENL----DLKLTPYKVLATSTRHGFVQFIDSVSvaeavaaegSIHN 746
Cdd:COG5032   1793 DGKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGIIEWVPNSD---------TLHS 1863

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  747 YFRKYHPQENGPY--------------GIAPDI------------------------------MDSYVRSCAGYCVITYL 782
Cdd:COG5032   1864 ILREYHKRKNISIdqekklaarldnlkLLLKDEfftkatlksppvlydwfsesfpnpedwltaRTNFARSLAVYSVIGYI 1943

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  783 LGVGDRHLDNLLLT-TCGKLFHIDFGYILGRDPKPLPPPMKL----SKEMVEAMGGVNSEhyQEFRKQCYTAFLHLRRHA 857
Cdd:COG5032   1944 LGLGDRHPGNILIDrSSGHVIHIDFGFILFNAPGRFPFPEKVpfrlTRNIVEAMGVSGVE--GSFRELCETAFRALRKNA 2021

                          410       420       430       440       450       460       470
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1573060031  858 NLMLNLFSLMIDASV------PDIALEPDKAVRKVQDKFRLDLGEEEAVHYIQYLIDSSVTAVMPAIVEQFHKITQYIR 930
Cdd:COG5032   2022 DSLMNVLELFVRDPLiewrrlPCFREIQNNEIVNVLERFRLKLSEKDAEKFVDLLINKSVESLITQATDPFQLATMYIG 2100
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 284-410 1.11e-48

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: 170.59  E-value: 1.11e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 284 KEAKPNATIRDILNTIVSYPSTKPLSNEEQDHVWKFRFYLSTQKKALAKFLKCVNWTQQNEVRQALSMMRIWVPMDVEDA 363
Cdd:pfam00613   1 KDLKPNEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYLMLVPKALTKLLLSVKWSDLSEVAEALSLLLKWAPIDPVDA 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1573060031 364 LELLSPNFTHPAVRKYAISRLQQAPDEDILLYLLQLVQALKYENFKN 410
Cdd:pfam00613  81 LELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHD 127
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 55-198 1.66e-41

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: 148.28  E-value: 1.66e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  55 CSDLMVVCQIFDQNQPLALPVSTSYKAF-TSRWSWNEWLTLPIQFNDLPRTAQLALTIYDC-IGPNKLWPVGGTTISLFS 132
Cdd:pfam00792   2 QEDLYVECQLYHGGKPLCLPVSTRYVPFsNSSIKWNEWITFPIQISDLPRSARLCITIWDVsGPEKSFVPIGWVNTSLFD 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1573060031 133 KHGLFRQGMVDLRVFPnreadgnfPTETPGkakDQGKEQMQRLTKLTKKHRNGHMTKVDWLDRLTF 198
Cdd:pfam00792  82 KKGILRQGKQKLRLWP--------SKSTPG---RSNVDEMNRLEKLLKKYERGQVSSVDWLDFLTF 136
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 22-119 2.18e-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: 2.18e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031   22 IKIGTLEG-KRQKPEYDKLLADPILKYSGLCqdgcSDLMVVCQIFDQNQPLALPVSTSYKAFTSRWSWNEWLTLPIQFND 100
Cdd:smart00142   1 VKIESLWDcDRNLVITIALIHGIPLNWSRDY----SDLYVEIQLYHGGKLLCLPVSTSYKPFFPSVKWNEWLTFPIQISD 76

                           90
                   ....*....|....*....
gi 1573060031  101 LPRTAQLALTIYDCIGPNK 119
Cdd:smart00142  77 LPREARLCITIYAVKNPSK 95
PTZ00303 PTZ00303
phosphatidylinositol kinase; Provisional
 683-810 1.58e-04

phosphatidylinositol kinase; Provisional


Pssm-ID: 140324 [Multi-domain]  Cd Length: 1374  Bit Score: 45.85  E-value: 1.58e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  683 DDLRQDQLILQMITLMDKLLRKENLDLKLTPYKVLATSTRHGFVQfidsvsvaeavAAEGsihnyfRKYHPQENgpYGIA 762
Cdd:PTZ00303  1059 ENVERDQLMCISSRLLQMLLSSEIGNAEMLDYSVLPLSCDSGLIE-----------KAEG------RELSNLDN--MDIA 1119

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1573060031  763 PDIMDSYVRSCAGYC-------VITYLLGVGDRHLDNLLLTTCGKLFHIDFGYIL 810
Cdd:PTZ00303  1120 SYVLYRGTRSCINFLasaklflLLNYIFSIGDRHKGNVLIGTNGALLHIDFRFIF 1174
 
Name Accession Description Interval E-value
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 584-927 0e+00

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: 582.57  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 584 LSQQQKFIDNLVKLVKSVLRESGNRKKKAEKLQQLLFDPtaFKFNFSNFEPIPFPLDPDIIIKGIIPEKASLFKSALMPS 663
Cdd:cd00896     4 LKRQQEFVDRLRSLMKEVKNEKGSRDKKIERLRELLSDS--ELGLLLFFEPLPLPLDPSVKVTGIIPEKSTVFKSALMPL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 664 KLHFITADNSEYVAIFKHGDDLRQDQLILQMITLMDKLLRKENLDLKLTPYKVLATSTRHGFVQFID-SVSVAEAVAAEG 742
Cdd:cd00896    82 KLTFKTLDGGEYKVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVPnSKALADILKKYG 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 743 SIHNYFRKYHPQENGPYGIAPDIMDSYVRSCAGYCVITYLLGVGDRHLDNLLLTTCGKLFHIDFGYILGRDPKPLPPPMK 822
Cdd:cd00896   162 SILNFLRKHNPDESGPYGIKPEVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHIDFGYILGRDPKPFPPPMK 241

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 823 LSKEMVEAMGGVNSEHYQEFRKQCYTAFLHLRRHANLMLNLFSLMIDASVPDIALEPDKAVRKVQDKFRLDLGEEEAVHY 902
Cdd:cd00896   242 LCKEMVEAMGGANSEGYKEFKKYCCTAYNILRKHANLILNLFSLMVDANIPDIALEPDKAVLKVQEKFRLDLSDEEAEQY 321

                         330       340
                  ....*....|....*....|....*
gi 1573060031 903 IQYLIDSSVTAVMPAIVEQFHKITQ 927
Cdd:cd00896   322 FQNLIDESVNALFPAVVETIHKIAQ 346
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 581-910 2.33e-111

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: 345.71  E-value: 2.33e-111
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 581 RLNLSQQQKFIDNLVKLVKSVLRESGNRKKkaEKLQQLLFdptafkfNFSNFEPIPFPLDPDIIIKGIIPEKASLFKSAL 660
Cdd:cd00891     1 REELLKQVKVLDELKEIAKKIKEEPSEERK--EVLEKLLQ-------KLELPKKFTLPLDPRMEVKGLIVEKCKVMDSKK 71

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 661 MPSKLHFITADNS--EYVAIFKHGDDLRQDQLILQMITLMDKLLRKENLDLKLTPYKVLATSTRHGFVQFI-DSVSVAEA 737
Cdd:cd00891    72 LPLWLVFKNADPGgdPIKVIFKAGDDLRQDQLTLQLLRIMDKLWKKEGLDLRMTPYKCIATGDEVGMIEVVpNSETTAAI 151

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 738 VAAEG---------SIHNYFRKYHPQENgPYGIApdiMDSYVRSCAGYCVITYLLGVGDRHLDNLLLTTCGKLFHIDFGY 808
Cdd:cd00891   152 QKKYGgfgaafkdtPISNWLKKHNPTEE-EYEEA---VENFIRSCAGYCVATYVLGIGDRHNDNIMVTKSGHLFHIDFGH 227

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 809 ILGRDPKPLPPPMKL-----SKEMVEAMGGVNSEHYQEFRKQCYTAFLHLRRHANLMLNLFSLMIDASVPDiaLEPDKAV 883
Cdd:cd00891   228 FLGNFKKKFGIKRERapfvfTPEMAYVMGGEDSENFQKFEDLCCKAYNILRKHGNLLINLFSLMLSAGIPE--LQSIEDI 305

                         330       340
                  ....*....|....*....|....*..
gi 1573060031 884 RKVQDKFRLDLGEEEAVHYIQYLIDSS 910
Cdd:cd00891   306 EYLRDALQLDLSDEEAAEHFRKLIHES 332
C2_PI3K_class_III cd08397
C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 27-186 3.31e-71

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: 232.14  E-value: 3.31e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  27 LEGKRQKPEYDKLLADPILKYSGLCQDGCSDLMVVCQIFDQNQPLALPVSTSYKAFTSRWSWNEWLTLPIQFNDLPRTAQ 106
Cdd:cd08397     1 LEGKVPLLSLSEKLEDPVLRFSGSNVSPNSDLFVTCQVFDDGKPLTLPVQTSYKPFKNRRNWNEWLTLPIKYSDLPRNSQ 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 107 LALTIYDCIGPNKLWPVGGTTISLFSKHGLFRQGMVDLRVFPNREADGNFPTeTPGKAKDQGKEQMQRLTKLTKKHRNGH 186
Cdd:cd08397    81 LAITIWDVSGTGKAVPFGGTTLSLFNKDGTLRRGRQKLRVWPDVEADGSIPT-STGKSPDSERDELDRLEKLLKKYERGE 159
PI3Ka_III cd00870
Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is ...
 283-544 4.03e-71

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: 232.22  E-value: 4.03e-71
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 283 DKEAKPNATIRDILNTIVSYPSTKPLSNEEQDHVWKFRFYLSTQKKALAKFLKCVNWTQQNEVRQALSMMRIWVPMDVED 362
Cdd:cd00870     1 DKDLKPNSKERKELNKILKYPPTTKLTDEEKDLIWKFRFYLTNNKKALTKFLKSVNWSDEQEVKQALELMPKWAKIDIED 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 363 ALELLSPNFTHPAVRKYAISRLQQAPDEDILLYLLQLVQALKYENFKNIQEGYARvspgrdniivheekeaqlekkdske 442
Cdd:cd00870    81 ALELLSPYFTNPVVRKYAVSRLKLASDEELLLYLLQLVQALKYENLDLSPLPRLD------------------------- 135

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 443 snstitnesvmhrsssynqadqiassnansvievdvdprpaslpenilqnvytdsantdtlqdhmneeeevQDLATFLIQ 522
Cdd:cd00870   136 -----------------------------------------------------------------------SPLADFLIE 144

                         250       260
                  ....*....|....*....|..
gi 1573060031 523 RSCKNAKLANYFYWYLLIECED 544
Cdd:cd00870   145 RALKNPKLANFLYWYLKVELED 166
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 587-927 2.46e-65

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: 223.32  E-value: 2.46e-65
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 587 QQKFIDNLVKLVKSVLRESGNRKKKAekLQQLLfDPTAFKFNFSNFEpipFPLDPDIIIKGIIPEKASLFKSALMPSKLH 666
Cdd:cd05166     7 QHVLVQALTSIAEKVKSAKDSARENA--LRREL-EQLASFLLENSFR---LPLDPALEVTGVDVRSCSYFNSNALPLKLV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 667 FITAD--NSEYVAIFKHGDDLRQDQLILQMITLMDKLLRKENLDLKLTPYKVLATSTRHGFVQFI-DSVSVAEAVAAEGS 743
Cdd:cd05166    81 FRNADprAEPISVIFKVGDDLRQDMLTLQLIRIMDKIWLQEGLDLKMITFRCVPTGNKRGMVELVpEAETLREIQTEHGL 160

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 744 --------IHNYFRKYHPQENgPYGIApdiMDSYVRSCAGYCVITYLLGVGDRHLDNLLLTTCGKLFHIDFGYILG---- 811
Cdd:cd05166   161 tgsfkdrpLADWLQKHNPSEL-EYEKA---VENFIRSCAGYCVATYVLGICDRHNDNIMLKTSGHLFHIDFGKFLGdaqm 236

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 812 -----RDpkplPPPMKLSKEMVEAM--GGVNSEHYQEFRKQCYTAFLHLRRHANLMLNLFSLMIDASVPDIALEpdkAVR 884
Cdd:cd05166   237 fgnfkRD----RVPFVLTSDMAYVIngGDKPSSRFQLFVDLCCQAFNIIRKNSNLLLNLLSLMLSSGIPGVTQD---DLR 309

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|...
gi 1573060031 885 KVQDKFRLDLGEEEAVHYIQYLIDSSVTAVMPAIVEQFHKITQ 927
Cdd:cd05166   310 YVQDALLPELTDAEATAHFTRMIEESLSSKFTQLNFFIHNLAQ 352
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 584-904 2.51e-65

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: 223.67  E-value: 2.51e-65
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 584 LSQQQKFIDNLVKLvKSVLRESGNRKKKAEKLQQLLFDPTAFKFNFSNFepiPFPLDPDIIIKGIIPEKASLFKSALMPS 663
Cdd:cd05165     4 LSRQVEALNKLKKL-SDILKEKKKSKEKVKKLLKECLKQKFYDEALQNF---QSPLNPSHKLGELIIEKCKVMDSKKRPL 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 664 KLHFITAD-----NSEYVAIFKHGDDLRQDQLILQMITLMDKLLRKENLDLKLTPYKVLATSTRHGFVQFI-DSVSVAE- 736
Cdd:cd05165    80 WLVFENADplalsGEDIKIIFKNGDDLRQDMLTLQIIRIMDNIWKEEGLDLRMLPYGCLSTGDNVGLIEVVrNAKTIANi 159

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 737 -------AVAA--EGSIHNYFRKYHPQENGpYGIApdiMDSYVRSCAGYCVITYLLGVGDRHLDNLLLTTCGKLFHIDFG 807
Cdd:cd05165   160 qkkkgkvATLAfnKDSLHKWLKEKNKTGEK-YDRA---IEEFTLSCAGYCVATYVLGIGDRHSDNIMVKENGQLFHIDFG 235

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 808 YILG---------RDPKPLPPPMKLSKEMVEAMGGVNSEHYQEFRKQCYTAFLHLRRHANLMLNLFSLMIDASVPDIALE 878
Cdd:cd05165   236 HFLGnfkkkfgikRERVPFVLTHDFVYVIARGQDNTKSEEFQEFQELCEKAYLILRRHGNLFISLFSMMLSTGIPELTSV 315

                         330       340
                  ....*....|....*....|....*.
gi 1573060031 879 PDkaVRKVQDKFRLDLGEEEAVHYIQ 904
Cdd:cd05165   316 KD--IEYLRKTLALDKTEEEALKYFR 339
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 678-879 2.29e-62

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: 211.00  E-value: 2.29e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  678 IFKHGDDLRQDQLILQMITLMDKLLRKE----NLDLKLTPYKVLATSTRHGFVQFI-DSVSVAE---------------- 736
Cdd:smart00146   2 IFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVpNSTTLHEilkeyrkqkgkvldlr 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  737 -----------------AVAAEGSIHNYFRKYHPQENGPYgiaPDIMDSYVRSCAGYCVITYLLGVGDRHLDNLLLTTCG 799
Cdd:smart00146  82 sqtatrlkklelfleatGKFPDPVLYDWFTKKFPDPSEDY---FEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTG 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  800 KLFHIDFGYILGRDPKPLPPPMKL----SKEMVEAMGgvNSEHYQEFRKQCYTAFLHLRRHANLMLNLFSLMIDASVPDI 875
Cdd:smart00146 159 HLFHIDFGFILGNGPKLFGFPERVpfrlTPEMVDVMG--DSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLPDW 236


                   ....
gi 1573060031  876 ALEP 879
Cdd:smart00146 237 RSGK 240
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 674-875 1.06e-56

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: 195.63  E-value: 1.06e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 674 EYVAIFKHGDDLRQDQLILQMITLMDKLLRKENLDLK-LTPYKVLATSTRHGFVQFIDSVSVA----------------- 735
Cdd:pfam00454   1 GYGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLRrLKPYSVIPLGPKCGIIEWVPNSETLayildeygengvpptam 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 736 --------------------EAVAAEGSIHNYFRKYHPQENGPYgiapDIMDSYVRSCAGYCVITYLLGVGDRHLDNLLL 795
Cdd:pfam00454  81 vkilhsalnypklklefesrISLPPKVGLLQWFVKKSPDAEEWG----EARKNFVRSCAGYSVLDYILGNGDRHLDNILV 156

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 796 -TTCGKLFHIDFGYILGRDPKPLPPPMKL----SKEMVEAMGgvNSEHYQEFRKQCYTAFLHLRRHANLMLNLFSLMIDA 870
Cdd:pfam00454 157 dKTTGKLFHIDFGLCLPDAGKDLPFPEKVpfrlTREMVYAMG--PSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVAD 234


                  ....*
gi 1573060031 871 SVPDI 875
Cdd:pfam00454 235 GLPDW 239
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 289-572 2.56e-56

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: 192.09  E-value: 2.56e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  289 NATIRDILNTIVSYPSTKPLSNEEQDHVWKFRFYLSTQ-KKALAKFLKCVNWTQQNEVRQALSMMRIWVPMDVEDALELL 367
Cdd:smart00145   4 DIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTNnPKALPKFLLSVKWSDADEVAQALSLLLSWAPLDPEDALELL 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  368 SPNFTHPAVRKYAISRLQQAPDEDILLYLLQLVQALKYENFKNiqegyarvspgrdniivheekeaqlekkdskesnsti 447
Cdd:smart00145  84 DPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLD------------------------------------- 126

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  448 tnesvmhrsssynqadqiassnansvievdvdprpaslpenilqnvytdsantdtlqdhmneeeevQDLATFLIQRSCKN 527
Cdd:smart00145 127 ------------------------------------------------------------------SALARFLLERALAN 140

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*.
gi 1573060031  528 AKLANYFYWYLLIECEDPEptMKQNI-LIRELYLTVMKTFSQTLAK 572
Cdd:smart00145 141 QRLGHFFYWYLKSELHDPH--VSIRFgLLLEAYLRGCGTHLKELLK 184
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
516-930 2.55e-51

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 196.93  E-value: 2.55e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  516 LATFLIQRSCKNAKLANYF--YWYLLIECEdpeptmkqNILIRELYLTVMKTFSQTLAKGSPEMQKKRLNLsqQQKFIDN 593
Cdd:COG5032   1643 LAQLLSRLSSENNKISVALliDKPLHEERE--------NFPSGLSLSSFQSSFLKELIKKSPRKIRKKFKI--DISLLNL 1712

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  594 LVKLVKSVLRESGNRKKKAEKLQQLLFDPTAFKF--NFSNFEPIPFPLDPDIIIKGIIPEKASLFKSALM-PSKLHFITA 670
Cdd:COG5032   1713 SRKLYISVLRSIRKRLKRLLELRLKKVSPKLLLFhaFLEIKLPGQYLLDKPFVLIERFEPEVSVVKSHLQrPRRLTIRGS 1792

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  671 DNSEYVAIFKHGDDLRQDQLILQMITLMDKLLRKENL----DLKLTPYKVLATSTRHGFVQFIDSVSvaeavaaegSIHN 746
Cdd:COG5032   1793 DGKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGIIEWVPNSD---------TLHS 1863

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  747 YFRKYHPQENGPY--------------GIAPDI------------------------------MDSYVRSCAGYCVITYL 782
Cdd:COG5032   1864 ILREYHKRKNISIdqekklaarldnlkLLLKDEfftkatlksppvlydwfsesfpnpedwltaRTNFARSLAVYSVIGYI 1943

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  783 LGVGDRHLDNLLLT-TCGKLFHIDFGYILGRDPKPLPPPMKL----SKEMVEAMGGVNSEhyQEFRKQCYTAFLHLRRHA 857
Cdd:COG5032   1944 LGLGDRHPGNILIDrSSGHVIHIDFGFILFNAPGRFPFPEKVpfrlTRNIVEAMGVSGVE--GSFRELCETAFRALRKNA 2021

                          410       420       430       440       450       460       470
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1573060031  858 NLMLNLFSLMIDASV------PDIALEPDKAVRKVQDKFRLDLGEEEAVHYIQYLIDSSVTAVMPAIVEQFHKITQYIR 930
Cdd:COG5032   2022 DSLMNVLELFVRDPLiewrrlPCFREIQNNEIVNVLERFRLKLSEKDAEKFVDLLINKSVESLITQATDPFQLATMYIG 2100
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 576-911 1.39e-50

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: 182.47  E-value: 1.39e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 576 EMQKKRLNLSQQQKFIDNLVKLVKSVLRESGNRKKKAEKLQQllfdpTAFKFNFSNFEPipfPLDPDIIIKGIIPEKASL 655
Cdd:cd05173     2 KVLSKQVEALNKLKTLNSLIKLNAVKLSKAKGKEAMHTCLRQ-----SAYREALSDLQS---PLNPSIILSELNVEKCKY 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 656 FKSALMPSklhFITADNSEYVA-----IFKHGDDLRQDQLILQMITLMDKLLRKENLDLKLTPYKVLATSTRHGFVQFI- 729
Cdd:cd05173    74 MDSKMKPL---WIVYNNKLFGGdslgiIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVPYGCLATGDRSGLIEVVs 150

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 730 ----------DSVSVAEAVA-AEGSIHNYFRKYHPQENGPYGIapdimDSYVRSCAGYCVITYLLGVGDRHLDNLLLTTC 798
Cdd:cd05173   151 saetiadiqlNSSNVAAAAAfNKDALLNWLKEYNSGDDLERAI-----EEFTLSCAGYCVATYVLGIGDRHSDNIMVRKN 225

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 799 GKLFHIDFGYILG---------RDPKPLPPPMKLSKEMVEAMGGvNSEHYQEFRKQCYTAFLHLRRHANLMLNLFSLMID 869
Cdd:cd05173   226 GQLFHIDFGHILGnfkskfgikRERVPFILTYDFIHVIQQGKTG-NTEKFGRFRQYCEDAYLILRKNGNLFITLFALMLT 304

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|..
gi 1573060031 870 ASVPDiaLEPDKAVRKVQDKFRLDLGEEEAVHYIQYLIDSSV 911
Cdd:cd05173   305 AGLPE--LTSVKDIQYLKDSLALGKSEEEALKQFRQKFDEAL 344
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
 678-929 2.78e-50

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: 179.21  E-value: 2.78e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 678 IFKHGDDLRQDQLILQMITLMDKLLRKENLDLKLTPYKVLATSTRHGFVQFI-DSVSV---AEAVAAEGSIHNYFRKYHP 753
Cdd:cd05168    34 IVKSGDDLRQELLAMQLIKQFQRIFEEAGLPLWLRPYEILVTSSDSGLIETIpDTVSIdslKKRFPNFTSLLDYFERTFG 113

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 754 QENGPYGIAPdiMDSYVRSCAGYCVITYLLGVGDRHLDNLLLTTCGKLFHIDFGYILGrdpkplpppmkLS--------- 824
Cdd:cd05168   114 DPNSERFKEA--QRNFVESLAAYSLVCYLLQIKDRHNGNILLDSEGHIIHIDFGFMLS-----------NSpgglgfeta 180

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 825 -----KEMVEAMGGVNSEHYQEFRKQCYTAFLHLRRHANLMLNLFSLMIDAS-VPDIALEPDKAVRKVQDKFRLDLGEEE 898
Cdd:cd05168   181 pfkltQEYVEVMGGLESDMFRYFKTLMIQGFLALRKHADRIVLLVEIMQQGSkLPCFFGGGEFTIEQLRERFKLNLTEEE 260

                         250       260       270
                  ....*....|....*....|....*....|.
gi 1573060031 899 AVHYIQYLIDSSVTAVMPAIVEQFHKITQYI 929
Cdd:cd05168   261 CAQFVDSLIDKSLNNWRTRQYDNFQYLTNGI 291
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 638-904 7.24e-50

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: 180.63  E-value: 7.24e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 638 PLDPDIIIKGIIPEKASLFKSALMPSKLHFitadNSEYVA------IFKHGDDLRQDQLILQMITLMDKLLRKENLDLKL 711
Cdd:cd05174    59 PLDPSIILEEVCVDQCTFMDSKMKPLWIMY----SSEEAGagnvgiIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRM 134

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 712 TPYKVLATSTRHGFVQFI------------DSVSVAEAVAAEGSIHNYFRKYHPQENGPYGIapdimDSYVRSCAGYCVI 779
Cdd:cd05174   135 TPYGCLSTGDKTGLIEVVlhsdtianiqlnKSNMAATAAFNKDALLNWLKSKNPGDALDQAI-----EEFTLSCAGYCVA 209

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 780 TYLLGVGDRHLDNLLLTTCGKLFHIDFGYILG---------RDPKPLPPPMKLSKEMVEAMGGvNSEHYQEFRKQCYTAF 850
Cdd:cd05174   210 TYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGnfktkfginRERVPFILTYDFVHVIQQGKTN-NSEKFERFRGYCERAY 288

                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1573060031 851 LHLRRHANLMLNLFSLMIDASVPDiaLEPDKAVRKVQDKFRLDLGEEEAVHYIQ 904
Cdd:cd05174   289 TILRRHGLLFLHLFALMKAAGLPE--LSCSKDIQYLKDSLALGKTEEEALKHFR 340
PI3Ka cd00864
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 290-410 6.17e-49

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: 170.09  E-value: 6.17e-49
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 290 ATIRDILNTIVSYPSTKPLSNEEQDHVWKFRFYLSTQKKALAKFLKCVNWTQQNEVRQALSMMRIWVPMDVEDALELLSP 369
Cdd:cd00864     1 AWERKPLLAILLYPPFSTLTEEEKELLWKFRYYLLNVPKALPKLLKSVNWNDDEEVSELYQLLKWWAPLSPEDALELLSP 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 1573060031 370 NFTHPAVRKYAISRLQQAPDEDILLYLLQLVQALKYENFKN 410
Cdd:cd00864    81 KYPDPVVRQYAVRVLESASDDELLLYLPQLVQALKYEPYLD 121
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 284-410 1.11e-48

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: 170.59  E-value: 1.11e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 284 KEAKPNATIRDILNTIVSYPSTKPLSNEEQDHVWKFRFYLSTQKKALAKFLKCVNWTQQNEVRQALSMMRIWVPMDVEDA 363
Cdd:pfam00613   1 KDLKPNEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYLMLVPKALTKLLLSVKWSDLSEVAEALSLLLKWAPIDPVDA 80

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 1573060031 364 LELLSPNFTHPAVRKYAISRLQQAPDEDILLYLLQLVQALKYENFKN 410
Cdd:pfam00613  81 LELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHD 127
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
 644-929 5.41e-48

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: 173.16  E-value: 5.41e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 644 IIKGIIPEKASLFKSA----LM----------PSKLHFITADNSEYV----AIFKHGDDLRQDQLILQMITLMDKLLRKE 705
Cdd:cd05167     1 VVLGIDYKSGKPLQSAakapFLvtfkvkdcgvDELEHEGTESEATKEvwqaAIFKVGDDCRQDMLALQLISLFKNIFEEV 80

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 706 NLDLKLTPYKVLATSTRHGFVQFI-DSVSVAE-AVAAEGSIHNYFR-KYHPQENGPYGIApdiMDSYVRSCAGYCVITYL 782
Cdd:cd05167    81 GLDLYLFPYRVVATGPGCGVIEVIpNSKSRDQiGRETDNGLYEYFLsKYGDESTPAFQKA---RRNFIKSMAGYSLVSYL 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 783 LGVGDRHLDNLLLTTCGKLFHIDFGYIL----GRDPKPLPPPMKLSKEMVEAMGG-VNSEHYQEFRKQCYTAFLHLRRHA 857
Cdd:cd05167   158 LQIKDRHNGNIMIDDDGHIIHIDFGFIFeispGGNLGFESAPFKLTKEMVDLMGGsMESEPFKWFVELCVRGYLAVRPYA 237

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1573060031 858 NLMLNLFSLMIDASVPDIAlepDKAVRKVQDKFRLDLGEEEAVHYIQYLIDSSVTAVMPAIVEQFHKITQYI 929
Cdd:cd05167   238 EAIVSLVELMLDSGLPCFR---GQTIKNLRERFALEMSEREAANFMIKLIADSYLKIRTKGYDMFQYYQNGI 306
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 584-927 1.04e-47

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: 173.92  E-value: 1.04e-47
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 584 LSQQQKFIDNLVKLVKSVLRESGNR-----KKKAEKLQQLlfdptafkfnFSNFEPIPFPLDPDIIIKGIIPEKASLFKS 658
Cdd:cd05177     4 FSKETKLISILIDAAEKVKTASDTRrkevlKREASRLEDF----------FQDVVSCCLPLNPALRVKGIDADACSYFTS 73

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 659 ALMPSKLHFITAD--NSEYVAIFKHGDDLRQDQLILQMITLMDKLLRKENLDLKLTPYKVLATSTRHGFVQFI-DSVSVA 735
Cdd:cd05177    74 NAAPLKISFINANplAKNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYRCLSTGKTQGLVQMVpDAVTLA 153

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 736 EAVAAEGSI----HNYFRKYHPQENGPYGIAPDIMDSYVRSCAGYCVITYLLGVGDRHLDNLLLTTCGKLFHIDFGYILG 811
Cdd:cd05177   154 KIHRESGLIgplkENTIEKWFHMHNKLKEDYDKAVRNFFHSCAGWCVVTFILGVCDRHNDNIMLTHSGHMFHIDFGKFLG 233

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 812 ---------RDPKPLPPPMKLSKEMVEamGGVNSEHYQEFRKQCYTAFLHLRRHANLMLNLFSLMIDASVPDIALEPDka 882
Cdd:cd05177   234 haqtfgsikRDRAPFIFTSEMEYFITE--GGKKPQRFQRFVELCCRAYNIVRKHSQLLLNLLEMMLHAGLPELKDIQD-- 309

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*
gi 1573060031 883 VRKVQDKFRLDLGEEEAVHYIQYLIDSSVTAVMPAIVEQFHKITQ 927
Cdd:cd05177   310 LKYVYNNLRPQDTDLEATSYFTKKIKESLECFPVKLNNLIHTLAQ 354
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 609-903 3.66e-46

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: 170.04  E-value: 3.66e-46
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 609 KKKAEKLQQLLFdPTAFKFnfsnfepipfPLDPDIIIKGIIPEKASLFKSALMPSKLHFITAD----NSEYVAI-FKHGD 683
Cdd:cd00894    40 KQKLENLQNSQL-PESFRV----------PYDPGLRAGALVIEKCKVMASKKKPLWLEFKCADptalSNETIGIiFKHGD 108

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 684 DLRQDQLILQMITLMDKLLRKENLDLKLTPYKVLATSTRHGFVQFI-DSVSVAE----AVAAEGSIHNYFRKYHPQENGP 758
Cdd:cd00894   109 DLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVkDATTIAKiqqsTVGNTGAFKDEVLNHWLKEKCP 188

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 759 YGIA-PDIMDSYVRSCAGYCVITYLLGVGDRHLDNLLLTTCGKLFHIDFGYILGRdpkpLPPPMKLSKEMVE-------- 829
Cdd:cd00894   189 IEEKfQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHILGN----YKSFLGINKERVPfvltpdfl 264

                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1573060031 830 ----AMGGVNSEHYQEFRKQCYTAFLHLRRHANLMLNLFSLMIDASVPDIALEPDkaVRKVQDKFRLDLGEEEAVHYI 903
Cdd:cd00894   265 fvmgTSGKKTSLHFQKFQDVCVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKED--IEYIRDALTVGKSEEDAKKHF 340
PI3Kc_C2_alpha cd05176
Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 581-927 1.12e-45

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: 168.23  E-value: 1.12e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 581 RLNLSQQQKFIDNLVKLVKSVLRESGNRKKKAekLQ------QLLFDPTAFKFnfsnfepipfPLDPDIIIKGIIPEKAS 654
Cdd:cd05176     1 REELEKQTRLVQLLGRVAEKVRQASGSARQVA--LQdgmervQSFFQKNKCRL----------PLSPSLVAKELNIKACS 68

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 655 LFKSALMPSKLHFITAD--NSEYVAIFKHGDDLRQDQLILQMITLMDKLLRKENLDLKLTPYKVLATSTRHGFVQFIDSV 732
Cdd:cd05176    69 FFSSNAVPLKVALVNADplGEEINVMFKVGEDLRQDMLALQMIKIMDKIWLQEGLDLRMVIFKCLSTGKDRGMVELVPSS 148

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 733 SVAEAVAAE----GSIHN-----YFRKYHPQENgPYGIAPDimdSYVRSCAGYCVITYLLGVGDRHLDNLLLTTCGKLFH 803
Cdd:cd05176   149 DTLRKIQVEygvtGSFKDkplaeWLRKYNPSEE-EYEKASE---NFIYSCAGCCVATYVLGICDRHNDNIMLRSTGHMFH 224

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 804 IDFGYILG---------RDpkplPPPMKLSKEMVEAMGGVN--SEHYQEFRKQCYTAFLHLRRHANLMLNLFSLMIDASV 872
Cdd:cd05176   225 IDFGKFLGhaqmfgsfkRD----RAPFVLTSDMAYVINGGEkpTIRFQLFVDLCCQAYNLIRKHTNLFLNLLSLMLSSGL 300

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1573060031 873 PDIALEPDkaVRKVQDKFRLDLGEEEAVHYIQYLIDSSVTAVMPAIVEQFHKITQ 927
Cdd:cd05176   301 PELTGIQD--LKYVFDALQPQTTDAEATIFFTRLIESSLGSVATKFNFFIHNLAQ 353
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
 677-912 3.28e-45

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: 164.36  E-value: 3.28e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 677 AIFKHGDDLRQDQLILQMITLMDKLLRKENLDLKLTPYKVLATSTRHGFVQFI-DSVSVAE------AVAAEGSIHNYFR 749
Cdd:cd00893    30 LIVKTGDDLKQEQLALQLISQFDQIFKEEGLPLWLRPYEILSLGPDSGIIEMIkNAVSIDSlkkkldSFNKFVSLSDFFD 109

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 750 KYHPQENGPYGIapdimDSYVRSCAGYCVITYLLGVGDRHLDNLLLTTCGKLFHIDFGYILG---RDPKPLPPPMKLSKE 826
Cdd:cd00893   110 DNFGDEAIQKAR-----DNFLQSLVAYSLVCYFLQIKDRHNGNILLDKEGHIIHIDFGFFLSshpGFYGFEGAPFKLSSE 184

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 827 MVEAMGGVNSEHYQEFRKQCYTAFLHLRRHANLMLNLFSLMIDASVPDIALEpdKAVRKVQDKFRLDLGEEEAVHYIQYL 906
Cdd:cd00893   185 YIEVLGGVDSELFKEFRKLFLKGFMALRKHSDKILSLVEMMYSGHGITCFGK--KTIQQLKQRFNPELTEGELEVYVLSL 262


                  ....*.
gi 1573060031 907 IDSSVT 912
Cdd:cd00893   263 INKSLD 268
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 581-927 6.63e-44

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: 162.86  E-value: 6.63e-44
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 581 RLNLSQQQKFIDNLVKLVKSVlRESGNRKKKAeKLQQLLFDPTAFkfnFSNFEPIPFPLDPDIIIKGIIPEKASLFKSAL 660
Cdd:cd00895     1 REEFDRQCWLVNVLAKLAQQV-REAAPSARQG-ILREGLEEVKQF---FSINGSCRLPLSPSLLVKGIVPRDCSYFNSNA 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 661 MPSKLHFITADN--SEYVAIFKHGDDLRQDQLILQMITLMDKLLRKENLDLKLTPYKVLATSTRHGFVQFIDSVSVAEAV 738
Cdd:cd00895    76 VPLKLSFQNVDPlgENIRVIFKCGDDLRQDMLTLQMIRIMNKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKI 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 739 AAEGSIHNYFR---------KYHPQENgPYGIApdiMDSYVRSCAGYCVITYLLGVGDRHLDNLLLTTCGKLFHIDFGYI 809
Cdd:cd00895   156 QVEHGVTGSFKdrpladwlqKHNPTED-EYEKA---VENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRF 231

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 810 LGR-----DPKPLPPPMKLSKEMVEAMGGVN--SEHYQEFRKQCYTAFLHLRRHANLMLNLFSLMIDASVPDIALEPDka 882
Cdd:cd00895   232 LGHaqmfgNIKRDRAPFVFTSDMAYVINGGDkpSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLED-- 309

                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*
gi 1573060031 883 VRKVQDKFRLDLGEEEAVHYIQYLIDSSVTAVMPAIVEQFHKITQ 927
Cdd:cd00895   310 LKYVYDALRPQDTEADATTYFTRLIESSLGSVATKLNFFIHNLAQ 354
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 55-198 1.66e-41

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: 148.28  E-value: 1.66e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  55 CSDLMVVCQIFDQNQPLALPVSTSYKAF-TSRWSWNEWLTLPIQFNDLPRTAQLALTIYDC-IGPNKLWPVGGTTISLFS 132
Cdd:pfam00792   2 QEDLYVECQLYHGGKPLCLPVSTRYVPFsNSSIKWNEWITFPIQISDLPRSARLCITIWDVsGPEKSFVPIGWVNTSLFD 81

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1573060031 133 KHGLFRQGMVDLRVFPnreadgnfPTETPGkakDQGKEQMQRLTKLTKKHRNGHMTKVDWLDRLTF 198
Cdd:pfam00792  82 KKGILRQGKQKLRLWP--------SKSTPG---RSNVDEMNRLEKLLKKYERGQVSSVDWLDFLTF 136
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 583-902 1.44e-35

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: 139.04  E-value: 1.44e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 583 NLSQQQKFIDNLVKLVKSVLREsgnRKKKAEKLQQLLFDPTAFKFNFSN-FEPIPFPLDPDIIIKGIIPEKASLFKSALM 661
Cdd:cd05175     7 HLSRQVEAMEKLINLTDILKQE---KKDETQKVQMKFLVEQMRRPDFMDaLQGFLSPLNPAHQLGNLRLEECRIMSSAKR 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 662 PSKLHFITAD--------NSEYvaIFKHGDDLRQDQLILQMITLMDKLLRKENLDLKLTPYKVLATSTRHGFVQFIDSVS 733
Cdd:cd05175    84 PLWLNWENPDimsellfqNNEI--IFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSH 161

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 734 VAEAVAAEG-----------SIHNYFRKYHPQEngpygIAPDIMDSYVRSCAGYCVITYLLGVGDRHLDNLLLTTCGKLF 802
Cdd:cd05175   162 TIMQIQCKGglkgalqfnshTLHQWLKDKNKGE-----IYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLF 236

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 803 HIDFGYIL-------GRDPKPLPPPMKLSKEMVEAMGG---VNSEHYQEFRKQCYTAFLHLRRHANLMLNLFSLMIDASV 872
Cdd:cd05175   237 HIDFGHFLdhkkkkfGYKRERVPFVLTQDFLIVISKGAqecTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGM 316

                         330       340       350
                  ....*....|....*....|....*....|
gi 1573060031 873 PDIALEPDKAVrkVQDKFRLDLGEEEAVHY 902
Cdd:cd05175   317 PELQSFDDIAY--IRKTLALDKTEQEALEY 344
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
 648-869 1.98e-33

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: 128.22  E-value: 1.98e-33
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 648 IIPEKASLFKSALMPSKLHFITADNSEYVAIFKHGDDLRQDQLILQMITLMDKLLRKENLDLKLTPYKVLATSTRHGFVQ 727
Cdd:cd00142     3 LDVGILKVIHSKQRPKKITLIGADGKTYSFLLKRRDDLRKDERSFQFMRLIQSILEKESVNLVLPPYKVIPLSENSGLIE 82

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 728 FI-DSVSVAEAVAAegsihnYFRKyHPQENGPYgiapDIMDSYVRSCAGYCVITYLLGVGDRHLDNLLLTTCGKLFHIDF 806
Cdd:cd00142    83 IVkDAQTIEDLLKS------LWRK-SPSSQSWL----NRRENFSCSLAGYSVLGYIFGIGDRHPSNIMIEPSGNIFHIDF 151

                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1573060031 807 GYILGRDPKPLPPPMKL---SKEMVEAMGGVNseHYQEFRKQCYTAFLHLRRHANLMLNLFSLMID 869
Cdd:cd00142   152 GFIFSGRKLAEGVETVPfrlTPMLENAMGTAG--VNGPFQISMVKIMEILREHADLIVPILEHSLR 215
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 292-410 1.37e-32

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: 124.35  E-value: 1.37e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 292 IRDILNTIVSYPSTKPLSNEEQDHVWKFRFYLSTQKKALAKFLKCVNWTQQNEVRQALSMMRIWVPMDVEDALELLSPNF 371
Cdd:cd00872     3 EREQLEAIIARDPLSELTEEDKELLWKLRHECRKKPQALPKLLLSVKWNKRDDVAQMYQLLKRWPKLKPEQALELLDCNF 82

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1573060031 372 THPAVRKYAISRLQQAPDEDILLYLLQLVQALKYENFKN 410
Cdd:cd00872    83 PDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHD 121
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 22-119 2.18e-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: 2.18e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031   22 IKIGTLEG-KRQKPEYDKLLADPILKYSGLCqdgcSDLMVVCQIFDQNQPLALPVSTSYKAFTSRWSWNEWLTLPIQFND 100
Cdd:smart00142   1 VKIESLWDcDRNLVITIALIHGIPLNWSRDY----SDLYVEIQLYHGGKLLCLPVSTSYKPFFPSVKWNEWLTFPIQISD 76

                           90
                   ....*....|....*....
gi 1573060031  101 LPRTAQLALTIYDCIGPNK 119
Cdd:smart00142  77 LPREARLCITIYAVKNPSK 95
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
 645-868 1.08e-24

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: 103.12  E-value: 1.08e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 645 IKGIIPEkASLFKSALMPSKLHFITADNSEYVAIFKHGDDLRQDQLILQMITLMDKLLRKEN----LDLKLTPYKVLATS 720
Cdd:cd05164     1 IASFDPR-VRILASLQKPKKITILGSDGKEYPFLVKGDDDLRKDERVMQLFQLLNTLLEKDKetrkRNLTIRTYSVVPLS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 721 TRHGFVQFIDSVsvaeaVAAEGSIHNYFRKYHPQENGPYgiapDIMDSYVRSCAGYCVITYLLGVGDRHLDNLLL-TTCG 799
Cdd:cd05164    80 SQSGLIEWVDNT-----TTLKPVLKKWFNETFPDPTQWY----EARSNYTKSTAVMSMVGYIIGLGDRHLENILIdTKTG 150

                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1573060031 800 KLFHIDFGYILGRDPKPLPPPMK---LSKEMVEAMGGVNSEhyQEFRKQCYTAFLHLRRHANLMLNLFSLMI 868
Cdd:cd05164   151 EVVHIDFGMIFNKGKTLPVPEIVpfrLTRNIINGMGPTGVE--GLFRKSCEQVLRVFRKHKDKLITFLDTFL 220
C2_PI3K_like cd08380
C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes ...
 44-183 1.22e-24

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: 100.90  E-value: 1.22e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  44 ILKYSGLCQDGCSDLMVVCQIFDQNQPLALPVSTSYKAFTSRWSWNEWLTLPIQFNDLPRTAQLALTIY--DCIGPNKLW 121
Cdd:cd08380    16 GITNINLLDSEDLKLYVRVQLYHGGEPLCPPQSTKKVPFSTSVTWNEWLTFDILISDLPREARLCLSIYavSEPGSKKEV 95

                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1573060031 122 PVGGTTISLFSKHGLFRQGMVDLRVFPNREADGNfPTETPGKakdQGKEQMQRLTKLTKKHR 183
Cdd:cd08380    96 PLGWVNVPLFDYKGKLRQGMITLNLWPGKKTDPR-IACTPCN---NSNENSTRLLIELPEFS 153
PIKKc_DNA-PK cd05172
Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, ...
 651-811 4.71e-24

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: 101.88  E-value: 4.71e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 651 EKASLFKSALMPSKLHFITADNSEYVAIFKHGDDLRQDQLILQMITLMDKLLRKE----NLDLKLTPYKVLATSTRHGFV 726
Cdd:cd05172     6 PRVLVLSSKRRPKRITIRGSDEKEYKFLVKGGEDLRQDQRIQQLFDVMNNILASDpacrQRRLRIRTYQVIPMTSRLGLI 85

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 727 QFIDSVSVAEAVAAEGSIHNYFRKyhpqengpygIAPD------IMDSYVRSCAGYCVITYLLGVGDRHLDNLLL-TTCG 799
Cdd:cd05172    86 EWVDNTTPLKEILENDLLRRALLS----------LASSpeaflaLRSNFARSLAAMSICGYILGIGDRHLSNFLVdLSTG 155

                         170
                  ....*....|..
gi 1573060031 800 KLFHIDFGYILG 811
Cdd:cd05172   156 RLIGIDFGHAFG 167
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
 662-861 5.13e-19

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: 88.37  E-value: 5.13e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 662 PSKLHFITADNSEYVAIFKHGDDLRQDQLILQMITLMDKLLRKE----NLDLKLTPYKVLATSTRHGFVQFID-SVSVAE 736
Cdd:cd05171    17 PKIITCIGSDGKKYKQLVKGGDDLRQDAVMEQVFELVNQLLKRDketrKRKLRIRTYKVVPLSPRSGVLEFVEnTIPLGE 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 737 AVAAEGSIHNYFRKYHPQENGPYGIA-------------------------------------PDIMD------SYVRSC 773
Cdd:cd05171    97 YLVGASSKSGAHARYRPKDWTASTCRkkmrekakasaeerlkvfdeicknfkpvfrhfflekfPDPSDwferrlAYTRSV 176

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 774 AGYCVITYLLGVGDRHLDNLLL-TTCGKLFHIDFGYI----------------LGRDpkplpppmklskeMVEAMG--GV 834
Cdd:cd05171   177 ATSSIVGYILGLGDRHLNNILIdQKTGELVHIDLGIAfeqgkllpipetvpfrLTRD-------------IVDGMGitGV 243

                         250       260
                  ....*....|....*....|....*..
gi 1573060031 835 NSehyqEFRKQCYTAFLHLRRHANLML 861
Cdd:cd05171   244 EG----VFRRCCEETLRVLRENKEALL 266
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 645-872 7.50e-17

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: 81.01  E-value: 7.50e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 645 IKGIIPEkASLFKSALMPSKLHFITADNSEYVAIFKHGDDLRQDQLILQMITLMDKLLRK----ENLDLKLTPYKVLATS 720
Cdd:cd00892     1 ISGFEDE-VEIMPSLQKPKKITLVGSDGKKYPFLCKPKDDLRKDARMMEFNTLINRLLSKdpesRRRNLHIRTYAVIPLN 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 721 TRHGFVQFIDSVSVAEAVAAE---GSIHNYFRKYHPQENGPYgiapDIMDSYVRSCAGYCVITYLLGVGDRHLDNLLL-T 796
Cdd:cd00892    80 EECGIIEWVPNTVTLRSILSTlypPVLHEWFLKNFPDPTAWY----EARNNYTRSTAVMSMVGYILGLGDRHGENILFdS 155

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 797 TCGKLFHIDFGYILGRDPKPLPppmklsKE---------MVEAMG--GVNSehyqEFRKQCYTAFLHLRRHAN-LMLNLF 864
Cdd:cd00892   156 TTGDVVHVDFDCLFDKGLTLEV------PErvpfrltqnMVDAMGvtGVEG----TFRRTCEVTLRVLRENREtLMSVLE 225


                  ....*...
gi 1573060031 865 SLMIDASV 872
Cdd:cd00892   226 TFVHDPLV 233
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
 304-406 5.53e-15

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: 73.65  E-value: 5.53e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 304 STKPLSNEEQDHVWKFRFYLSTQKKALAKFLKCV-NWTQQNeVRQALSMMRIWVPMDVEDALELLSPNFTHPAVRKYAIS 382
Cdd:cd00869    15 STYTLSTEDKDLLWEKRLYCTNEPNALPLVLASApSWDWAN-LMDVYQLLHQWAPLRPLIALELLLPKFPDQEVRAHAVQ 93

                          90       100
                  ....*....|....*....|....
gi 1573060031 383 RLQQAPDEDILLYLLQLVQALKYE 406
Cdd:cd00869    94 WLARLSNDELLDYLPQLVQALKFE 117
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 645-807 9.98e-12

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: 66.74  E-value: 9.98e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 645 IKGIIPeKASLFKSALMPSKLHFITADNSEYVAIFKHGDDLRQDQLILQMITLMDKLLRKENL----DLKLTPYKVLATS 720
Cdd:cd05169     1 ISSFDP-TLEVITSKQRPRKLTIVGSDGKEYKFLLKGHEDLRLDERVMQLFGLVNTLLKNDSEtsrrNLSIQRYSVIPLS 79

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 721 TRHGFVQFID----------------SVSV-AEAVAAEGSIHNY-----FRKY----HPQENGPygiAPDIMDS------ 768
Cdd:cd05169    80 PNSGLIGWVPgcdtlhslirdyrekrKIPLnIEHRLMLQMAPDYdnltlIQKVevfeYALENTP---GDDLRRVlwlksp 156

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1573060031 769 -----------YVRSCAGYCVITYLLGVGDRHLDNLLL-TTCGKLFHIDFG 807
Cdd:cd05169   157 sseawlerrtnFTRSLAVMSMVGYILGLGDRHPSNIMLdRLTGKVIHIDFG 207
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
 662-806 5.53e-11

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: 64.58  E-value: 5.53e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 662 PSKLHFITADNSEYVAIFKHGDDLRQDQLILQMITLMDKLLRKENL----DLKLTPYKVLATSTRHGFVQFIDSV----- 732
Cdd:cd05170    17 PKKLVFLGSDGKRYPYLFKGLEDLHLDERIMQFLSIVNAMLASDNEhrrrRYRARHYSVTPLGPRSGLIQWVDGAtplfs 96

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 733 -------------SVAEAVAAEGSIH------NYFRKYHP--QENG----------PYGI------------APDIM--- 766
Cdd:cd05170    97 lykrwqqrraaaqAQKNQDSGSTPPPvprpseLFYNKLKPalKAAGirkstsrrewPLEVlrqvleelvaetPRDLLare 176

                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1573060031 767 ---------------DSYVRSCAGYCVITYLLGVGDRHLDNLLLT-TCGKLFHIDF 806
Cdd:cd05170   177 lwcsspssaewwrvtQRFARSLAVMSMIGYIIGLGDRHLDNILVDlSTGEVVHIDY 232
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 60-140 1.33e-08

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: 55.06  E-value: 1.33e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  60 VVCQIFDQNQPLALPVST----SYKAFTSRWSWNEWLTLPIQFNDLPRTAQLALTIYDCIGPNKLW---------PVGGT 126
Cdd:cd04012    33 LSCSLYHGGRLLCSPVTTkpvkITKSFFPRVVWDEWIEFPIPVCQLPRESRLVLTLYGTTSSPDGGsnkqrmgpeELGWV 112

                          90
                  ....*....|....
gi 1573060031 127 TISLFSKHGLFRQG 140
Cdd:cd04012   113 SLPLFDFRGVLRQG 126
PI4Ka cd00871
Phosphoinositide 4-kinase(PI4K), accessory domain (PIK domain); PIK domain is conserved in PI3 ...
 305-429 5.80e-08

Phosphoinositide 4-kinase(PI4K), 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. PI4K phosphorylates hydroxylgroup at position 4 on the inositol ring of phosphoinositide, the first commited step in the phosphatidylinositol cycle.


Pssm-ID: 238443  Cd Length: 175  Bit Score: 53.51  E-value: 5.80e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 305 TKPLSNEEQDHVWKFRFYLSTQKKALAKFLKcvnWTQQNEVRQALSMMRIWVPMDVEDALELLSPNF-THPAVRKYAISR 383
Cdd:cd00871    18 NSKLKSEVTRLVRKHPLAVVKIPEALPFLVT---GKSVDENSPDLKYLLYWAPVSPVQALSLFTPQYpGHPLVLQYAVRV 94

                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1573060031 384 LQQAPDEDILLYLLQLVQALKYENFKNIqEGYARVSPGRDNIIVHE 429
Cdd:cd00871    95 LESYPVETVFFYIPQIVQALRYDKMGYV-EEYILETAKRSQLFAHQ 139
C2_PI3K_class_I_alpha cd08398
C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 64-148 1.76e-05

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: 45.94  E-value: 1.76e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  64 IFDQNQPLALPVSTSYKAFTSRWsWNEWLTLPIQFNDLPRTAQLALTIYDCIGPNKL----WPVGGTTISLFSKHGLFRQ 139
Cdd:cd08398    34 IYHGGEPLCDNVNTQRVPCSNPR-WNEWLDYDIYIPDLPRSARLCLSICSVKGRKGAkeehCPLAWGNINLFDYTDTLVS 112


                  ....*....
gi 1573060031 140 GMVDLRVFP 148
Cdd:cd08398   113 GKMALNLWP 121
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
 678-807 9.73e-05

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: 43.20  E-value: 9.73e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031 678 IFKHGDDlRQDQLILQMITLMDKLLRKENLDLklTPYKVLATSTRHGFvqfidSVSVAEaVAAEGSIHNYFRKYHPQENG 757
Cdd:cd13968    22 AVKIGDD-VNNEEGEDLESEMDILRRLKGLEL--NIPKVLVTEDVDGP-----NILLME-LVKGGTLIAYTQEEELDEKD 92

                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1573060031 758 PYGIapdimdsyVRSCAGYCVITYLLGV--GDRHLDNLLLTTCGKLFHIDFG 807
Cdd:cd13968    93 VESI--------MYQLAECMRLLHSFHLihRDLNNDNILLSEDGNVKLIDFG 136
PTZ00303 PTZ00303
phosphatidylinositol kinase; Provisional
 683-810 1.58e-04

phosphatidylinositol kinase; Provisional


Pssm-ID: 140324 [Multi-domain]  Cd Length: 1374  Bit Score: 45.85  E-value: 1.58e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  683 DDLRQDQLILQMITLMDKLLRKENLDLKLTPYKVLATSTRHGFVQfidsvsvaeavAAEGsihnyfRKYHPQENgpYGIA 762
Cdd:PTZ00303  1059 ENVERDQLMCISSRLLQMLLSSEIGNAEMLDYSVLPLSCDSGLIE-----------KAEG------RELSNLDN--MDIA 1119

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1573060031  763 PDIMDSYVRSCAGYC-------VITYLLGVGDRHLDNLLLTTCGKLFHIDFGYIL 810
Cdd:PTZ00303  1120 SYVLYRGTRSCINFLasaklflLLNYIFSIGDRHKGNVLIGTNGALLHIDFRFIF 1174
C2_PI3K_class_I_gamma cd08399
C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 77-187 3.51e-03

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: 39.51  E-value: 3.51e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1573060031  77 TSYKAFTSRWSWNEWLTLPIQFNDLPRTAQLALTIYdCIGPNKLWPVGGTTISLFS---KHGLFRqgMVDLRVFPNREA- 152
Cdd:cd08399    50 TSPKPFTEEVLWNTWLEFDIKIKDLPKGALLNLQIY-CGKAPALSSKKSAESPSSEskgKHQLLY--YVNLLLIDHRFLl 126

                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 1573060031 153 -DGNFPTET---PGKAKDQGKEQMQRLTKLTKKHRNGHM 187
Cdd:cd08399   127 rTGEYVLHMwqiSGKGEDQGSVNADKLTSATNPDKENSM 165
 
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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