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Conserved domains on  [gi|21237725|ref|NP_002640|]
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phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform [Homo sapiens]

Protein Classification

phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform( domain architecture ID 18341701)

phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform phosphorylates PtdIns(4,5)P2 (phosphatidylinositol 4,5-bisphosphate) to generate phosphatidylinositol 3,4,5-trisphosphate (PIP3)

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 729-1095 0e+00

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: 769.80  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  729 LHDFTQQVQVIEMLQKVTLDIKSLSAEKYDVSSQVISQLKQKLENLQNSQLPESFRVPYDPGLKAGALAIEKCKVMASKK 808
Cdd:cd00894    1 LHDFTQQVQVIEMLQKVTLDIKSLSAEKYDVSSQVISQLKQKLENLQNSQLPESFRVPYDPGLRAGALVIEKCKVMASKK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  809 KPLWLEFKCADPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTI 888
Cdd:cd00894   81 KPLWLEFKCADPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTI 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  889 AKIQQSTVGNTGAFKDEVLNHWLKEKSPTEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHI 968
Cdd:cd00894  161 AKIQQSTVGNTGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHI 240

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  969 LGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSPHFQKFQDICVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 1048
Cdd:cd00894  241 LGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSLHFQKFQDVCVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 320

                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....*..
gi 21237725 1049 EYIRDALTVGKNEEDAKKYFLDQIEVCRDKGWTVQFNWFLHLVLGIK 1095
Cdd:cd00894  321 EYIRDALTVGKSEEDAKKHFLDQIEVCRDKGWTVQFNWFLHLVLGIK 367
PIK3CG_ABD pfam19710
PIK3 catalytic subunit gamma adaptor-binding domain; This is the N-terminal domain from ...
 1-192 3.32e-113

PIK3 catalytic subunit gamma adaptor-binding domain; This is the N-terminal domain from PI3-kinase catalytic subunit gamma (PIK3CG, also known as p110 catalytic subunit gamma) which contains the adaptor-binding domain (ABD). This is a globular domain with an alpha/beta sandwich topology, common to all catalytic subunits of PIK3s, and it is similar to ubiquitin-like domains. This domain interacts with the regulatory subunit of the p101 type.


:

Pssm-ID: 466155  Cd Length: 195  Bit Score: 349.06  E-value: 3.32e-113
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725      1 MELENYKQPVVLREDNCRRRRRMKPRSAAASLSSMELIPIEFVLPTSQRKCKSPETALLHVAGHGNVEQMKAQVWLRALE 80
Cdd:pfam19710    4 MQLSDHEQPVVMREENRRRRRRMKKAFTSASSSSMELISIEFVLPTSNKNTKTPDTLLLEVAGNWTVEQVKAQVWLRAVE 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725     81 TSVAADFYHRLGPHHFLLLYQKKGQWYEIYDKYQVVQTLDCLRYWKATHRSPGQIHLVQRHPPSEESQAFQRQLTALIGY 160
Cdd:pfam19710   84 TNLCPDFYQKFSPDQFILLYQKKGQWYEIYDKHQVFQTLDCIRYWKALQKDVGKIHLVQRPQPSEESLQYQRQLNYLIGY 163

                          170       180       190
                   ....*....|....*....|....*....|..
gi 21237725    161 DVTDVSNVHDDELEFTRRGLVTPRMAEVASRD 192
Cdd:pfam19710  164 DVTDVSNVHDDELEFTRRKLVTPRMIELSDRD 195
C2_PI3K_class_I_gamma cd08399
C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 350-527 5.20e-113

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: 347.67  E-value: 5.20e-113
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  350 FTVSLWDCDRKFRVKIRGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFTEEVLWNVWLEFSIKIKDLPKGALL 429
Cdd:cd08399    1 FTVSLWDCDRKFRVKILGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFTEEVLWNTWLEFDIKIKDLPKGALL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  430 NLQIYCGKAPALSSKASAESPSSESKGKVQLLYYVNLLLIDHRFLLRRGEYVLHMWQISGKGEDQGSFNADKLTSATNPD 509
Cdd:cd08399   81 NLQIYCGKAPALSSKKSAESPSSESKGKHQLLYYVNLLLIDHRFLLRTGEYVLHMWQISGKGEDQGSVNADKLTSATNPD 160

                        170
                 ....*....|....*...
gi 21237725  510 KENSMSISILLDNYCHPI 527
Cdd:cd08399  161 KENSMSISILLDNYCHPV 178
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 549-725 1.96e-89

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: 284.21  E-value: 1.96e-89
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  549 NQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLARRevwdqSALDVGLTM 628
Cdd:cd00872    1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRKKPQALPKLLLSVKWNKRDDVAQMYQLLKRW-----PKLKPEQAL 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  629 QLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEIAQSRH 708
Cdd:cd00872   76 ELLDCNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSV 155

                        170
                 ....*....|....*..
gi 21237725  709 yQQRFAVILEAYLRGCG 725
Cdd:cd00872  156 -SQRFGLLLEAYLRGCG 171
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 203-312 2.17e-35

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


:

Pssm-ID: 197540  Cd Length: 108  Bit Score: 130.14  E-value: 2.17e-35
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725     203 TSKPLPEYLWKKIANNCIFIVIHRS--TTSQTIKVSPDDTPGAILQSFFTKMakkKSLMDIPESQSEqDFVLRVCGRDEY 280
Cdd:smart00144    1 TSPSVPEPLPLKTIANKILIVVHLEkdQQTKTLKVNPNCTPDSVLAQAFTKM---LSLHDQVDPTSE-DYILKVCGRDEY 76

                            90       100       110
                    ....*....|....*....|....*....|..
gi 21237725     281 LVGETPIKNFQWVRHCLKNGEEIHVVLDTPPD 312
Cdd:smart00144   77 LLGDHPLGSFEYIRNCLKNGTEPHLVLMTLSA 108
 
Name Accession Description Interval E-value
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 729-1095 0e+00

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: 769.80  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  729 LHDFTQQVQVIEMLQKVTLDIKSLSAEKYDVSSQVISQLKQKLENLQNSQLPESFRVPYDPGLKAGALAIEKCKVMASKK 808
Cdd:cd00894    1 LHDFTQQVQVIEMLQKVTLDIKSLSAEKYDVSSQVISQLKQKLENLQNSQLPESFRVPYDPGLRAGALVIEKCKVMASKK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  809 KPLWLEFKCADPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTI 888
Cdd:cd00894   81 KPLWLEFKCADPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTI 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  889 AKIQQSTVGNTGAFKDEVLNHWLKEKSPTEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHI 968
Cdd:cd00894  161 AKIQQSTVGNTGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHI 240

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  969 LGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSPHFQKFQDICVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 1048
Cdd:cd00894  241 LGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSLHFQKFQDVCVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 320

                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....*..
gi 21237725 1049 EYIRDALTVGKNEEDAKKYFLDQIEVCRDKGWTVQFNWFLHLVLGIK 1095
Cdd:cd00894  321 EYIRDALTVGKSEEDAKKHFLDQIEVCRDKGWTVQFNWFLHLVLGIK 367
PIK3CG_ABD pfam19710
PIK3 catalytic subunit gamma adaptor-binding domain; This is the N-terminal domain from ...
 1-192 3.32e-113

PIK3 catalytic subunit gamma adaptor-binding domain; This is the N-terminal domain from PI3-kinase catalytic subunit gamma (PIK3CG, also known as p110 catalytic subunit gamma) which contains the adaptor-binding domain (ABD). This is a globular domain with an alpha/beta sandwich topology, common to all catalytic subunits of PIK3s, and it is similar to ubiquitin-like domains. This domain interacts with the regulatory subunit of the p101 type.


Pssm-ID: 466155  Cd Length: 195  Bit Score: 349.06  E-value: 3.32e-113
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725      1 MELENYKQPVVLREDNCRRRRRMKPRSAAASLSSMELIPIEFVLPTSQRKCKSPETALLHVAGHGNVEQMKAQVWLRALE 80
Cdd:pfam19710    4 MQLSDHEQPVVMREENRRRRRRMKKAFTSASSSSMELISIEFVLPTSNKNTKTPDTLLLEVAGNWTVEQVKAQVWLRAVE 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725     81 TSVAADFYHRLGPHHFLLLYQKKGQWYEIYDKYQVVQTLDCLRYWKATHRSPGQIHLVQRHPPSEESQAFQRQLTALIGY 160
Cdd:pfam19710   84 TNLCPDFYQKFSPDQFILLYQKKGQWYEIYDKHQVFQTLDCIRYWKALQKDVGKIHLVQRPQPSEESLQYQRQLNYLIGY 163

                          170       180       190
                   ....*....|....*....|....*....|..
gi 21237725    161 DVTDVSNVHDDELEFTRRGLVTPRMAEVASRD 192
Cdd:pfam19710  164 DVTDVSNVHDDELEFTRRKLVTPRMIELSDRD 195
C2_PI3K_class_I_gamma cd08399
C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 350-527 5.20e-113

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: 347.67  E-value: 5.20e-113
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  350 FTVSLWDCDRKFRVKIRGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFTEEVLWNVWLEFSIKIKDLPKGALL 429
Cdd:cd08399    1 FTVSLWDCDRKFRVKILGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFTEEVLWNTWLEFDIKIKDLPKGALL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  430 NLQIYCGKAPALSSKASAESPSSESKGKVQLLYYVNLLLIDHRFLLRRGEYVLHMWQISGKGEDQGSFNADKLTSATNPD 509
Cdd:cd08399   81 NLQIYCGKAPALSSKKSAESPSSESKGKHQLLYYVNLLLIDHRFLLRTGEYVLHMWQISGKGEDQGSVNADKLTSATNPD 160

                        170
                 ....*....|....*...
gi 21237725  510 KENSMSISILLDNYCHPI 527
Cdd:cd08399  161 KENSMSISILLDNYCHPV 178
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 549-725 1.96e-89

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: 284.21  E-value: 1.96e-89
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  549 NQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLARRevwdqSALDVGLTM 628
Cdd:cd00872    1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRKKPQALPKLLLSVKWNKRDDVAQMYQLLKRW-----PKLKPEQAL 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  629 QLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEIAQSRH 708
Cdd:cd00872   76 ELLDCNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSV 155

                        170
                 ....*....|....*..
gi 21237725  709 yQQRFAVILEAYLRGCG 725
Cdd:cd00872  156 -SQRFGLLLEAYLRGCG 171
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 830-1046 6.45e-85

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: 274.95  E-value: 6.45e-85
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725     830 IIFKHGDDLRQDMLILQILRIMESIWETES----LDLCLLPYGCISTGDKIGMIEIVKDATTIAKIQ------------- 892
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDKetrrRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILkeyrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725     893 -----------QSTVGNTGAFKDEVLNHWLKEKSPTE-EKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNL 960
Cdd:smart00146   81 rsqtatrlkklELFLEATGKFPDPVLYDWFTKKFPDPsEDYFEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725     961 FHIDFGHILGNYKSFLGiNKERVPFVLTPDFLFVMGTSGkktspHFQKFQDICVKAYLALRHHTNLLIILFSMMLMTGMP 1040
Cdd:smart00146  161 FHIDFGFILGNGPKLFG-FPERVPFRLTPEMVDVMGDSG-----YFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLP 234


                    ....*.
gi 21237725    1041 QLTSKE 1046
Cdd:smart00146  235 DWRSGK 240
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 543-733 3.48e-78

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: 254.18  E-value: 3.48e-78
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725    543 VRAEMPNQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLARrevWDQsaL 622
Cdd:pfam00613    1 KDLKPNEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYLMLVPKALTKLLLSVKWSDLSEVAEALSLLLK---WAP--I 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725    623 DVGLTMQLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSE 702
Cdd:pfam00613   76 DPVDALELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSE 155

                          170       180       190
                   ....*....|....*....|....*....|.
gi 21237725    703 IaQSRHYQQRFAVILEAYLRGCGTAMLHDFT 733
Cdd:pfam00613  156 I-HDEEVSPRFGSLLELYLRSCGTSLLGLNK 185
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 828-1044 3.39e-74

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: 245.32  E-value: 3.39e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725    828 IGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLL-PYGCISTGDKIGMIEIVKDATTIAKIQQ----STVGNTGAF 902
Cdd:pfam00454    2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLRRLkPYSVIPLGPKCGIIEWVPNSETLAYILDeygeNGVPPTAMV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725    903 KD-----------------------EVLNHWLKEKSPTEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMI-TETG 958
Cdd:pfam00454   82 KIlhsalnypklklefesrislppkVGLLQWFVKKSPDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTTG 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725    959 NLFHIDFGHILGNYKSFLGINkERVPFVLTPDFLFVMGTSGkktspHFQKFQDICVKAYLALRHHTNLLIILFSMMLMTG 1038
Cdd:pfam00454  162 KLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAMGPSG-----DEGLFRELCETAYEALRRNLNLLTNLLKLMVADG 235


                   ....*.
gi 21237725   1039 MPQLTS 1044
Cdd:pfam00454  236 LPDWSI 241
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 545-732 9.57e-74

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: 241.78  E-value: 9.57e-74
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725     545 AEMPNQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLK-HPKAYPKLFSSVKWGQQEIVAKTYQLLARrevWDqsALD 623
Cdd:smart00145    1 KPLDIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTnNPKALPKFLLSVKWSDADEVAQALSLLLS---WA--PLD 75

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725     624 VGLTMQLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEI 703
Cdd:smart00145   76 PEDALELLDPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSEL 155

                           170       180
                    ....*....|....*....|....*....
gi 21237725     704 aQSRHYQQRFAVILEAYLRGCGTAMLHDF 732
Cdd:smart00145  156 -HDPHVSIRFGLLLEAYLRGCGTHLKELL 183
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
739-1085 2.59e-44

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 176.13  E-value: 2.59e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  739 IEMLQKVtldIKSLSAEKYDVSSQVISQLKQKLENLQ----------NSQLP--ESFRVPYDPGLKAGALAIEK-----C 801
Cdd:COG5032 1699 IRKKFKI---DISLLNLSRKLYISVLRSIRKRLKRLLelrlkkvspkLLLFHafLEIKLPGQYLLDKPFVLIERfepevS 1775

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  802 KVMASKKKPLWLEFKCADptalsNETIGIIFKHGDDLRQDMLILQILRIMESIW----ETESLDLCLLPYGCISTGDKIG 877
Cdd:COG5032 1776 VVKSHLQRPRRLTIRGSD-----GKLYSFIVKGGDDLRQDELALQLIRLMNKILkkdkETRRRDLWIRPYKVIPLSPGSG 1850

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  878 MIEIVKDATTIAKI------------------QQSTVGNTGAFKDE-----------VLNHWLKEKSPTEEKFQAAVERF 928
Cdd:COG5032 1851 IIEWVPNSDTLHSIlreyhkrknisidqekklAARLDNLKLLLKDEfftkatlksppVLYDWFSESFPNPEDWLTARTNF 1930

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  929 VYSCAGYCVATFVLGIGDRHNDNIMITE-TGNLFHIDFGHILGNYKSFLGINkERVPFVLTPDFLFVMGTSGKKTSphfq 1007
Cdd:COG5032 1931 ARSLAVYSVIGYILGLGDRHPGNILIDRsSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAMGVSGVEGS---- 2005

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725 1008 kFQDICVKAYLALRHHTNLLIILFSMML------------MTGMPQLTSKEDIEYIRDALTvgknEEDAKKYFL----DQ 1071
Cdd:COG5032 2006 -FRELCETAFRALRKNADSLMNVLELFVrdpliewrrlpcFREIQNNEIVNVLERFRLKLS----EKDAEKFVDllinKS 2080

                        410
                 ....*....|....
gi 21237725 1072 IEVCRdKGWTVQFN 1085
Cdd:COG5032 2081 VESLI-TQATDPFQ 2093
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 203-312 2.17e-35

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


Pssm-ID: 197540  Cd Length: 108  Bit Score: 130.14  E-value: 2.17e-35
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725     203 TSKPLPEYLWKKIANNCIFIVIHRS--TTSQTIKVSPDDTPGAILQSFFTKMakkKSLMDIPESQSEqDFVLRVCGRDEY 280
Cdd:smart00144    1 TSPSVPEPLPLKTIANKILIVVHLEkdQQTKTLKVNPNCTPDSVLAQAFTKM---LSLHDQVDPTSE-DYILKVCGRDEY 76

                            90       100       110
                    ....*....|....*....|....*....|..
gi 21237725     281 LVGETPIKNFQWVRHCLKNGEEIHVVLDTPPD 312
Cdd:smart00144   77 LLGDHPLGSFEYIRNCLKNGTEPHLVLMTLSA 108
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 203-312 2.71e-29

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


Pssm-ID: 395642  Cd Length: 106  Bit Score: 112.77  E-value: 2.71e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725    203 TSKPLPEYLwKKIANNCIFIVIH--RSTTSQTIKVSPDDTPGAILQSFFTKmakKKSLMDIPESQSeqDFVLRVCGRDEY 280
Cdd:pfam00794    1 ASTVSPEPL-PKLINNKLLISVHleGDQMTKTFTCNPNSTPGSLIAQALTK---KLSVHTQGDVTD--DYVLKVCGRDEY 74

                           90       100       110
                   ....*....|....*....|....*....|..
gi 21237725    281 LVGETPIKNFQWVRHCLKNGEEIHVVLDTPPD 312
Cdd:pfam00794   75 LLGDHPLGQFEYIRNCLKSGREPHLTLVEQSS 106
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 349-444 1.00e-27

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 107.82  E-value: 1.00e-27
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725     349 VFTVSLWDCDRKFRVKIRGIDIPVLPRNTDL-TVFVEANIQHGQQVLC-QRRTSPKPFTEEVLWNVWLEFSIKIKDLPKG 426
Cdd:smart00142    1 VKIESLWDCDRNLVITIALIHGIPLNWSRDYsDLYVEIQLYHGGKLLClPVSTSYKPFFPSVKWNEWLTFPIQISDLPRE 80

                            90
                    ....*....|....*...
gi 21237725     427 ALLNLQIYCGKAPALSSK 444
Cdd:smart00142   81 ARLCITIYAVKNPSKGSE 98
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 381-486 1.04e-09

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: 57.76  E-value: 1.04e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725    381 VFVEANIQHGQQVLCQR-RTSPKPF-TEEVLWNVWLEFSIKIKDLPKGALLNLQIYCGKAPalsskasaespssesKGKV 458
Cdd:pfam00792    5 LYVECQLYHGGKPLCLPvSTRYVPFsNSSIKWNEWITFPIQISDLPRSARLCITIWDVSGP---------------EKSF 69

                           90       100
                   ....*....|....*....|....*...
gi 21237725    459 QLLYYVNLLLIDHRFLLRRGEYVLHMWQ 486
Cdd:pfam00792   70 VPIGWVNTSLFDKKGILRQGKQKLRLWP 97
 
Name Accession Description Interval E-value
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 729-1095 0e+00

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: 769.80  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  729 LHDFTQQVQVIEMLQKVTLDIKSLSAEKYDVSSQVISQLKQKLENLQNSQLPESFRVPYDPGLKAGALAIEKCKVMASKK 808
Cdd:cd00894    1 LHDFTQQVQVIEMLQKVTLDIKSLSAEKYDVSSQVISQLKQKLENLQNSQLPESFRVPYDPGLRAGALVIEKCKVMASKK 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  809 KPLWLEFKCADPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTI 888
Cdd:cd00894   81 KPLWLEFKCADPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTI 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  889 AKIQQSTVGNTGAFKDEVLNHWLKEKSPTEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHI 968
Cdd:cd00894  161 AKIQQSTVGNTGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHI 240

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  969 LGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSPHFQKFQDICVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 1048
Cdd:cd00894  241 LGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSLHFQKFQDVCVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 320

                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....*..
gi 21237725 1049 EYIRDALTVGKNEEDAKKYFLDQIEVCRDKGWTVQFNWFLHLVLGIK 1095
Cdd:cd00894  321 EYIRDALTVGKSEEDAKKHFLDQIEVCRDKGWTVQFNWFLHLVLGIK 367
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 729-1091 0e+00

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: 602.70  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  729 LHDFTQQVQVIEMLQKVTLDIKSLSAEKydvsSQVISQLKQKLENLQNSQLPESFRVPYDPGLKAGALAIEKCKVMASKK 808
Cdd:cd05165    1 LKSLSRQVEALNKLKKLSDILKEKKKSK----EKVKKLLKECLKQKFYDEALQNFQSPLNPSHKLGELIIEKCKVMDSKK 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  809 KPLWLEFKCADPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTI 888
Cdd:cd05165   77 RPLWLVFENADPLALSGEDIKIIFKNGDDLRQDMLTLQIIRIMDNIWKEEGLDLRMLPYGCLSTGDNVGLIEVVRNAKTI 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  889 AKIQQSTVGN-TGAFKDEVLNHWLKEKSPTEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGH 967
Cdd:cd05165  157 ANIQKKKGKVaTLAFNKDSLHKWLKEKNKTGEKYDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVKENGQLFHIDFGH 236

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  968 ILGNYKSFLGINKERVPFVLTPDFLFVMGT-SGKKTSPHFQKFQDICVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKE 1046
Cdd:cd05165  237 FLGNFKKKFGIKRERVPFVLTHDFVYVIARgQDNTKSEEFQEFQELCEKAYLILRRHGNLFISLFSMMLSTGIPELTSVK 316

                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....*
gi 21237725 1047 DIEYIRDALTVGKNEEDAKKYFLDQIEVCRDKGWTVQFNWFLHLV 1091
Cdd:cd05165  317 DIEYLRKTLALDKTEEEALKYFRKKFNEALKGSWTTKVNWFFHNV 361
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 730-1077 0e+00

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: 537.15  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  730 HDFTQQVQVIEMLQKVTLDIKSLSAEKydvssqVISQLKQKLENLQnsqLPESFRVPYDPGLKAGALAIEKCKVMASKKK 809
Cdd:cd00891    2 EELLKQVKVLDELKEIAKKIKEEPSEE------RKEVLEKLLQKLE---LPKKFTLPLDPRMEVKGLIVEKCKVMDSKKL 72

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  810 PLWLEFKCADPTAlsnETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTIA 889
Cdd:cd00891   73 PLWLVFKNADPGG---DPIKVIFKAGDDLRQDQLTLQLLRIMDKLWKKEGLDLRMTPYKCIATGDEVGMIEVVPNSETTA 149

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  890 KIQQSTVGNTGAFKDEVLNHWLKEKSPTEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHIL 969
Cdd:cd00891  150 AIQKKYGGFGAAFKDTPISNWLKKHNPTEEEYEEAVENFIRSCAGYCVATYVLGIGDRHNDNIMVTKSGHLFHIDFGHFL 229

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  970 GNYKSFLGINKERVPFVLTPDFLFVMGtsGKKtSPHFQKFQDICVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDIE 1049
Cdd:cd00891  230 GNFKKKFGIKRERAPFVFTPEMAYVMG--GED-SENFQKFEDLCCKAYNILRKHGNLLINLFSLMLSAGIPELQSIEDIE 306

                        330       340
                 ....*....|....*....|....*...
gi 21237725 1050 YIRDALTVGKNEEDAKKYFLDQIEVCRD 1077
Cdd:cd00891  307 YLRDALQLDLSDEEAAEHFRKLIHESLN 334
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 730-1089 3.88e-127

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: 392.04  E-value: 3.88e-127
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  730 HDFTQQVQVIEMLQKVTLDIKSLSaekydvSSQVISQLKQKLENLQNSQLPESFRVPYDPGLKAGALAIEKCKVMASKKK 809
Cdd:cd05166    2 EEFLKQHVLVQALTSIAEKVKSAK------DSARENALRRELEQLASFLLENSFRLPLDPALEVTGVDVRSCSYFNSNAL 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  810 PLWLEFKCADPTAlsnETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTIA 889
Cdd:cd05166   76 PLKLVFRNADPRA---EPISVIFKVGDDLRQDMLTLQLIRIMDKIWLQEGLDLKMITFRCVPTGNKRGMVELVPEAETLR 152

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  890 KIQQStVGNTGAFKDEVLNHWLKEKSPTEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHIL 969
Cdd:cd05166  153 EIQTE-HGLTGSFKDRPLADWLQKHNPSELEYEKAVENFIRSCAGYCVATYVLGICDRHNDNIMLKTSGHLFHIDFGKFL 231

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  970 GNYKSFLGINKERVPFVLTPDFLFVMgTSGKKTSPHFQKFQDICVKAYLALRHHTNLLIILFSMMLMTGMPQLTSkEDIE 1049
Cdd:cd05166  232 GDAQMFGNFKRDRVPFVLTSDMAYVI-NGGDKPSSRFQLFVDLCCQAFNIIRKNSNLLLNLLSLMLSSGIPGVTQ-DDLR 309

                        330       340       350       360
                 ....*....|....*....|....*....|....*....|
gi 21237725 1050 YIRDALTVGKNEEDAKKYFLDQIEVCRdKGWTVQFNWFLH 1089
Cdd:cd05166  310 YVQDALLPELTDAEATAHFTRMIEESL-SSKFTQLNFFIH 348
PIK3CG_ABD pfam19710
PIK3 catalytic subunit gamma adaptor-binding domain; This is the N-terminal domain from ...
 1-192 3.32e-113

PIK3 catalytic subunit gamma adaptor-binding domain; This is the N-terminal domain from PI3-kinase catalytic subunit gamma (PIK3CG, also known as p110 catalytic subunit gamma) which contains the adaptor-binding domain (ABD). This is a globular domain with an alpha/beta sandwich topology, common to all catalytic subunits of PIK3s, and it is similar to ubiquitin-like domains. This domain interacts with the regulatory subunit of the p101 type.


Pssm-ID: 466155  Cd Length: 195  Bit Score: 349.06  E-value: 3.32e-113
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725      1 MELENYKQPVVLREDNCRRRRRMKPRSAAASLSSMELIPIEFVLPTSQRKCKSPETALLHVAGHGNVEQMKAQVWLRALE 80
Cdd:pfam19710    4 MQLSDHEQPVVMREENRRRRRRMKKAFTSASSSSMELISIEFVLPTSNKNTKTPDTLLLEVAGNWTVEQVKAQVWLRAVE 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725     81 TSVAADFYHRLGPHHFLLLYQKKGQWYEIYDKYQVVQTLDCLRYWKATHRSPGQIHLVQRHPPSEESQAFQRQLTALIGY 160
Cdd:pfam19710   84 TNLCPDFYQKFSPDQFILLYQKKGQWYEIYDKHQVFQTLDCIRYWKALQKDVGKIHLVQRPQPSEESLQYQRQLNYLIGY 163

                          170       180       190
                   ....*....|....*....|....*....|..
gi 21237725    161 DVTDVSNVHDDELEFTRRGLVTPRMAEVASRD 192
Cdd:pfam19710  164 DVTDVSNVHDDELEFTRRKLVTPRMIELSDRD 195
C2_PI3K_class_I_gamma cd08399
C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 350-527 5.20e-113

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: 347.67  E-value: 5.20e-113
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  350 FTVSLWDCDRKFRVKIRGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFTEEVLWNVWLEFSIKIKDLPKGALL 429
Cdd:cd08399    1 FTVSLWDCDRKFRVKILGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFTEEVLWNTWLEFDIKIKDLPKGALL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  430 NLQIYCGKAPALSSKASAESPSSESKGKVQLLYYVNLLLIDHRFLLRRGEYVLHMWQISGKGEDQGSFNADKLTSATNPD 509
Cdd:cd08399   81 NLQIYCGKAPALSSKKSAESPSSESKGKHQLLYYVNLLLIDHRFLLRTGEYVLHMWQISGKGEDQGSVNADKLTSATNPD 160

                        170
                 ....*....|....*...
gi 21237725  510 KENSMSISILLDNYCHPI 527
Cdd:cd08399  161 KENSMSISILLDNYCHPV 178
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 732-1091 2.06e-112

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: 353.50  E-value: 2.06e-112
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  732 FTQQVQVIEMLQKVTLDIK--SLSAEKYDVSSQVISQLKQK-----LENLQNsqlpesfrvPYDPGLKAGALAIEKCKVM 804
Cdd:cd05173    4 LSKQVEALNKLKTLNSLIKlnAVKLSKAKGKEAMHTCLRQSayreaLSDLQS---------PLNPSIILSELNVEKCKYM 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  805 ASKKKPLWLEFkcaDPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKD 884
Cdd:cd05173   75 DSKMKPLWIVY---NNKLFGGDSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVPYGCLATGDRSGLIEVVSS 151

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  885 ATTIAKIQ--QSTVGNTGAFKDEVLNHWLKEKSPTEEkFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFH 962
Cdd:cd05173  152 AETIADIQlnSSNVAAAAAFNKDALLNWLKEYNSGDD-LERAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFH 230

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  963 IDFGHILGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSPHFQKFQDICVKAYLALRHHTNLLIILFSMMLMTGMPQL 1042
Cdd:cd05173  231 IDFGHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQYCEDAYLILRKNGNLFITLFALMLTAGLPEL 310

                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....*....
gi 21237725 1043 TSKEDIEYIRDALTVGKNEEDAKKYFLDQIEVCRDKGWTVQFNWFLHLV 1091
Cdd:cd05173  311 TSVKDIQYLKDSLALGKSEEEALKQFRQKFDEALRESWTTKVNWMAHTV 359
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 786-1091 2.41e-112

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: 353.59  E-value: 2.41e-112
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  786 PYDPGLKAGALAIEKCKVMASKKKPLWLEFKCADPTAlsnETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLL 865
Cdd:cd05174   59 PLDPSIILEEVCVDQCTFMDSKMKPLWIMYSSEEAGA---GNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMT 135

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  866 PYGCISTGDKIGMIEIVKDATTIAKIQ--QSTVGNTGAFKDEVLNHWLKEKSPTEeKFQAAVERFVYSCAGYCVATFVLG 943
Cdd:cd05174  136 PYGCLSTGDKTGLIEVVLHSDTIANIQlnKSNMAATAAFNKDALLNWLKSKNPGD-ALDQAIEEFTLSCAGYCVATYVLG 214

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  944 IGDRHNDNIMITETGNLFHIDFGHILGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSPHFQKFQDICVKAYLALRHH 1023
Cdd:cd05174  215 IGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRH 294

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 21237725 1024 TNLLIILFSMMLMTGMPQLTSKEDIEYIRDALTVGKNEEDAKKYFLDQIEVCRDKGWTVQFNWFLHLV 1091
Cdd:cd05174  295 GLLFLHLFALMKAAGLPELSCSKDIQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNV 362
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 724-1091 4.93e-102

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: 326.24  E-value: 4.93e-102
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  724 CGTAMLHdFTQQVQVIEMLQKVTlDIksLSAEKYDVSSQVisQLKQKLENLQNSQLPES---FRVPYDPGLKAGALAIEK 800
Cdd:cd05175    1 CGMYLKH-LSRQVEAMEKLINLT-DI--LKQEKKDETQKV--QMKFLVEQMRRPDFMDAlqgFLSPLNPAHQLGNLRLEE 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  801 CKVMASKKKPLWLEFKCAD-PTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMI 879
Cdd:cd05175   75 CRIMSSAKRPLWLNWENPDiMSELLFQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLI 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  880 EIVKDATTIAKIQqSTVGNTGA--FKDEVLNHWLKEKSPTEeKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITET 957
Cdd:cd05175  155 EVVRNSHTIMQIQ-CKGGLKGAlqFNSHTLHQWLKDKNKGE-IYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDD 232

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  958 GNLFHIDFGHILGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSP--HFQKFQDICVKAYLALRHHTNLLIILFSMML 1035
Cdd:cd05175  233 GQLFHIDFGHFLDHKKKKFGYKRERVPFVLTQDFLIVISKGAQECTKtrEFERFQEMCYKAYLAIRQHANLFINLFSMML 312

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 21237725 1036 MTGMPQLTSKEDIEYIRDALTVGKNEEDAKKYFLDQIEVCRDKGWTVQFNWFLHLV 1091
Cdd:cd05175  313 GSGMPELQSFDDIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTI 368
PI3Kc_C2_alpha cd05176
Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 731-1089 3.66e-93

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: 301.51  E-value: 3.66e-93
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  731 DFTQQVQVIEMLQKVTLDIKSLSAEKYDVSsqvisqLKQKLENLQNSQLPESFRVPYDPGLKAGALAIEKCKVMASKKKP 810
Cdd:cd05176    3 ELEKQTRLVQLLGRVAEKVRQASGSARQVA------LQDGMERVQSFFQKNKCRLPLSPSLVAKELNIKACSFFSSNAVP 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  811 LWLEFKCADPTAlsnETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTIAK 890
Cdd:cd05176   77 LKVALVNADPLG---EEINVMFKVGEDLRQDMLALQMIKIMDKIWLQEGLDLRMVIFKCLSTGKDRGMVELVPSSDTLRK 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  891 IQQStVGNTGAFKDEVLNHWLKEKSPTEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHILG 970
Cdd:cd05176  154 IQVE-YGVTGSFKDKPLAEWLRKYNPSEEEYEKASENFIYSCAGCCVATYVLGICDRHNDNIMLRSTGHMFHIDFGKFLG 232

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  971 NYKSFLGINKERVPFVLTPDFLFVMgTSGKKTSPHFQKFQDICVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDIEY 1050
Cdd:cd05176  233 HAQMFGSFKRDRAPFVLTSDMAYVI-NGGEKPTIRFQLFVDLCCQAYNLIRKHTNLFLNLLSLMLSSGLPELTGIQDLKY 311

                        330       340       350
                 ....*....|....*....|....*....|....*....
gi 21237725 1051 IRDALTVGKNEEDAKKYFLDQIEVCRDKGWTvQFNWFLH 1089
Cdd:cd05176  312 VFDALQPQTTDAEATIFFTRLIESSLGSVAT-KFNFFIH 349
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 549-725 1.96e-89

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: 284.21  E-value: 1.96e-89
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  549 NQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLARRevwdqSALDVGLTM 628
Cdd:cd00872    1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRKKPQALPKLLLSVKWNKRDDVAQMYQLLKRW-----PKLKPEQAL 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  629 QLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEIAQSRH 708
Cdd:cd00872   76 ELLDCNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSV 155

                        170
                 ....*....|....*..
gi 21237725  709 yQQRFAVILEAYLRGCG 725
Cdd:cd00872  156 -SQRFGLLLEAYLRGCG 171
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 731-1073 1.26e-86

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: 284.09  E-value: 1.26e-86
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  731 DFTQQVQVIEMLQKVTLDIKSLS-AEKYDVSSQVISQLKQKLENLQnsqlpeSFRVPYDPGLKAGALAIEKCKVMASKKK 809
Cdd:cd05177    3 EFSKETKLISILIDAAEKVKTASdTRRKEVLKREASRLEDFFQDVV------SCCLPLNPALRVKGIDADACSYFTSNAA 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  810 PLWLEFKCADPTAlsnETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTIA 889
Cdd:cd05177   77 PLKISFINANPLA---KNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYRCLSTGKTQGLVQMVPDAVTLA 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  890 KIQQSTvGNTGAFKDEVLNHWLKEKSPTEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHIL 969
Cdd:cd05177  154 KIHRES-GLIGPLKENTIEKWFHMHNKLKEDYDKAVRNFFHSCAGWCVVTFILGVCDRHNDNIMLTHSGHMFHIDFGKFL 232

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  970 GNYKSFLGINKERVPFVLTPDFLFVMgTSGKKTSPHFQKFQDICVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDIE 1049
Cdd:cd05177  233 GHAQTFGSIKRDRAPFIFTSEMEYFI-TEGGKKPQRFQRFVELCCRAYNIVRKHSQLLLNLLEMMLHAGLPELKDIQDLK 311

                        330       340
                 ....*....|....*....|....
gi 21237725 1050 YIRDALTVGKNEEDAKKYFLDQIE 1073
Cdd:cd05177  312 YVYNNLRPQDTDLEATSYFTKKIK 335
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 830-1046 6.45e-85

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: 274.95  E-value: 6.45e-85
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725     830 IIFKHGDDLRQDMLILQILRIMESIWETES----LDLCLLPYGCISTGDKIGMIEIVKDATTIAKIQ------------- 892
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDKetrrRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILkeyrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725     893 -----------QSTVGNTGAFKDEVLNHWLKEKSPTE-EKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNL 960
Cdd:smart00146   81 rsqtatrlkklELFLEATGKFPDPVLYDWFTKKFPDPsEDYFEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725     961 FHIDFGHILGNYKSFLGiNKERVPFVLTPDFLFVMGTSGkktspHFQKFQDICVKAYLALRHHTNLLIILFSMMLMTGMP 1040
Cdd:smart00146  161 FHIDFGFILGNGPKLFG-FPERVPFRLTPEMVDVMGDSG-----YFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLP 234


                    ....*.
gi 21237725    1041 QLTSKE 1046
Cdd:smart00146  235 DWRSGK 240
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 731-1089 9.57e-85

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: 278.81  E-value: 9.57e-85
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  731 DFTQQVQVIEMLQKVTLDIKSLSAEkydvSSQVIsqLKQKLENL-QNSQLPESFRVPYDPGLKAGALAIEKCKVMASKKK 809
Cdd:cd00895    3 EFDRQCWLVNVLAKLAQQVREAAPS----ARQGI--LREGLEEVkQFFSINGSCRLPLSPSLLVKGIVPRDCSYFNSNAV 76

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  810 PLWLEFKCADPTAlsnETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTIA 889
Cdd:cd00895   77 PLKLSFQNVDPLG---ENIRVIFKCGDDLRQDMLTLQMIRIMNKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLR 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  890 KIQQSTvGNTGAFKDEVLNHWLKEKSPTEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHIL 969
Cdd:cd00895  154 KIQVEH-GVTGSFKDRPLADWLQKHNPTEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFL 232

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  970 GNYKSFLGINKERVPFVLTPDFLFVMgTSGKKTSPHFQKFQDICVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDIE 1049
Cdd:cd00895  233 GHAQMFGNIKRDRAPFVFTSDMAYVI-NGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLK 311

                        330       340       350       360
                 ....*....|....*....|....*....|....*....|
gi 21237725 1050 YIRDALTVGKNEEDAKKYFLDQIEVCRDKGWTvQFNWFLH 1089
Cdd:cd00895  312 YVYDALRPQDTEADATTYFTRLIESSLGSVAT-KLNFFIH 350
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
 794-1037 8.33e-82

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: 265.35  E-value: 8.33e-82
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  794 GALAIEKCKVMASKKKPLWLEFKCADptalsNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTG 873
Cdd:cd00142    1 NALDVGILKVIHSKQRPKKITLIGAD-----GKTYSFLLKRRDDLRKDERSFQFMRLIQSILEKESVNLVLPPYKVIPLS 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  874 DKIGMIEIVKDATTIakiqqstvgntgafkdEVLNHWLKEKSPTEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIM 953
Cdd:cd00142   76 ENSGLIEIVKDAQTI----------------EDLLKSLWRKSPSSQSWLNRRENFSCSLAGYSVLGYIFGIGDRHPSNIM 139

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  954 ITETGNLFHIDFGHILGNYKSFLGinKERVPFVLTPDFLFVMGTSGkktspHFQKFQDICVKAYLALRHHTNLLIILFSM 1033
Cdd:cd00142  140 IEPSGNIFHIDFGFIFSGRKLAEG--VETVPFRLTPMLENAMGTAG-----VNGPFQISMVKIMEILREHADLIVPILEH 212


                 ....
gi 21237725 1034 MLMT 1037
Cdd:cd00142  213 SLRD 216
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 734-1073 7.17e-81

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


Pssm-ID: 270628 [Multi-domain]  Cd Length: 346  Bit Score: 267.86  E-value: 7.17e-81
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  734 QQVQVIEMLQKVTLDIKSLSAEKydvsSQVISQLKQKLE--NLQNSQLPESFRVPYDPGLKAGALAIEKCKVMASKKKPL 811
Cdd:cd00896    6 RQQEFVDRLRSLMKEVKNEKGSR----DKKIERLRELLSdsELGLLLFFEPLPLPLDPSVKVTGIIPEKSTVFKSALMPL 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  812 WLEFKCADPtalsnETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTIAKI 891
Cdd:cd00896   82 KLTFKTLDG-----GEYKVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVPNSKALADI 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  892 QQSTvgntgafkDEVLNhWLKEKSPTEE----KFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGH 967
Cdd:cd00896  157 LKKY--------GSILN-FLRKHNPDESgpygIKPEVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHIDFGY 227

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  968 ILGN-YKSFLginkerVPFVLTPDFLFVMGtsGKKtSPHFQKFQDICVKAYLALRHHTNLLIILFSMMLMTGMP--QLTS 1044
Cdd:cd00896  228 ILGRdPKPFP------PPMKLCKEMVEAMG--GAN-SEGYKEFKKYCCTAYNILRKHANLILNLFSLMVDANIPdiALEP 298

                        330       340
                 ....*....|....*....|....*....
gi 21237725 1045 KEDIEYIRDALTVGKNEEDAKKYFLDQIE 1073
Cdd:cd00896  299 DKAVLKVQEKFRLDLSDEEAEQYFQNLID 327
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 543-733 3.48e-78

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: 254.18  E-value: 3.48e-78
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725    543 VRAEMPNQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLARrevWDQsaL 622
Cdd:pfam00613    1 KDLKPNEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYLMLVPKALTKLLLSVKWSDLSEVAEALSLLLK---WAP--I 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725    623 DVGLTMQLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSE 702
Cdd:pfam00613   76 DPVDALELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSE 155

                          170       180       190
                   ....*....|....*....|....*....|.
gi 21237725    703 IaQSRHYQQRFAVILEAYLRGCGTAMLHDFT 733
Cdd:pfam00613  156 I-HDEEVSPRFGSLLELYLRSCGTSLLGLNK 185
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 828-1044 3.39e-74

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: 245.32  E-value: 3.39e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725    828 IGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLL-PYGCISTGDKIGMIEIVKDATTIAKIQQ----STVGNTGAF 902
Cdd:pfam00454    2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLRRLkPYSVIPLGPKCGIIEWVPNSETLAYILDeygeNGVPPTAMV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725    903 KD-----------------------EVLNHWLKEKSPTEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMI-TETG 958
Cdd:pfam00454   82 KIlhsalnypklklefesrislppkVGLLQWFVKKSPDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTTG 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725    959 NLFHIDFGHILGNYKSFLGINkERVPFVLTPDFLFVMGTSGkktspHFQKFQDICVKAYLALRHHTNLLIILFSMMLMTG 1038
Cdd:pfam00454  162 KLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAMGPSG-----DEGLFRELCETAYEALRRNLNLLTNLLKLMVADG 235


                   ....*.
gi 21237725   1039 MPQLTS 1044
Cdd:pfam00454  236 LPDWSI 241
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 545-732 9.57e-74

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: 241.78  E-value: 9.57e-74
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725     545 AEMPNQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLK-HPKAYPKLFSSVKWGQQEIVAKTYQLLARrevWDqsALD 623
Cdd:smart00145    1 KPLDIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTnNPKALPKFLLSVKWSDADEVAQALSLLLS---WA--PLD 75

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725     624 VGLTMQLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEI 703
Cdd:smart00145   76 PEDALELLDPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSEL 155

                           170       180
                    ....*....|....*....|....*....
gi 21237725     704 aQSRHYQQRFAVILEAYLRGCGTAMLHDF 732
Cdd:smart00145  156 -HDPHVSIRFGLLLEAYLRGCGTHLKELL 183
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
 799-1095 5.49e-62

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: 213.61  E-value: 5.49e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  799 EKCKVMASKKK-PLWLEFKCADPTALSNETIGI------------IFKHGDDLRQDMLILQILRIMESIWETESLDLCLL 865
Cdd:cd05167    8 KSGKPLQSAAKaPFLVTFKVKDCGVDELEHEGTeseatkevwqaaIFKVGDDCRQDMLALQLISLFKNIFEEVGLDLYLF 87

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  866 PYGCISTGDKIGMIEIVKDATTIAKIQQSTVGNtgafkdevLNHWLKEK--SPTEEKFQAAVERFVYSCAGYCVATFVLG 943
Cdd:cd05167   88 PYRVVATGPGCGVIEVIPNSKSRDQIGRETDNG--------LYEYFLSKygDESTPAFQKARRNFIKSMAGYSLVSYLLQ 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  944 IGDRHNDNIMITETGNLFHIDFGHIL-----GNyksflgINKERVPFVLTPDFLFVMGtsGKKTSPHFQKFQDICVKAYL 1018
Cdd:cd05167  160 IKDRHNGNIMIDDDGHIIHIDFGFIFeispgGN------LGFESAPFKLTKEMVDLMG--GSMESEPFKWFVELCVRGYL 231

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 21237725 1019 ALRHHTNLLIILFSMMLMTGMPQLTsKEDIEYIRDALTVGKNEEDAKKYFLDQIEVCRDKGWTVQFNWFLHLVLGIK 1095
Cdd:cd05167  232 AVRPYAEAIVSLVELMLDSGLPCFR-GQTIKNLRERFALEMSEREAANFMIKLIADSYLKIRTKGYDMFQYYQNGIP 307
PI3Ka cd00864
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 549-703 5.47e-59

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


Pssm-ID: 238440  Cd Length: 152  Bit Score: 199.36  E-value: 5.47e-59
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  549 NQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLARREvwdqsALDVGLTM 628
Cdd:cd00864    1 AWERKPLLAILLYPPFSTLTEEEKELLWKFRYYLLNVPKALPKLLKSVNWNDDEEVSELYQLLKWWA-----PLSPEDAL 75

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 21237725  629 QLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEI 703
Cdd:cd00864   76 ELLSPKYPDPVVRQYAVRVLESASDDELLLYLPQLVQALKYEPYLDSYLARFLLERALKSQRLGHQLYWNLKSEI 150
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
 830-1094 1.66e-56

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: 197.48  E-value: 1.66e-56
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  830 IIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTIAKIQQSTvGNTGAFKDevLNH 909
Cdd:cd00893   30 LIVKTGDDLKQEQLALQLISQFDQIFKEEGLPLWLRPYEILSLGPDSGIIEMIKNAVSIDSLKKKL-DSFNKFVS--LSD 106

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  910 WLKEKSPTeEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHILGNYKSFLGInkERVPFVLTP 989
Cdd:cd00893  107 FFDDNFGD-EAIQKARDNFLQSLVAYSLVCYFLQIKDRHNGNILLDKEGHIIHIDFGFFLSSHPGFYGF--EGAPFKLSS 183

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  990 DFLFVMGtsGKKTSPhFQKFQDICVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDIEYIRDALTVGKNEEDAKKYFL 1069
Cdd:cd00893  184 EYIEVLG--GVDSEL-FKEFRKLFLKGFMALRKHSDKILSLVEMMYSGHGITCFGKKTIQQLKQRFNPELTEGELEVYVL 260

                        250       260
                 ....*....|....*....|....*
gi 21237725 1070 DQIEVCRDKGWTVQFNWFLHLVLGI 1094
Cdd:cd00893  261 SLINKSLDNWRTRWYDKYQYFSQGI 285
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
 828-1094 2.73e-55

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: 194.24  E-value: 2.73e-55
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  828 IGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTIAKIQQSTVGNTGafkdeVL 907
Cdd:cd05168   31 RSVIVKSGDDLRQELLAMQLIKQFQRIFEEAGLPLWLRPYEILVTSSDSGLIETIPDTVSIDSLKKRFPNFTS-----LL 105

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  908 NHWLKE-KSPTEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHILGNYKSflGINKERVPFV 986
Cdd:cd05168  106 DYFERTfGDPNSERFKEAQRNFVESLAAYSLVCYLLQIKDRHNGNILLDSEGHIIHIDFGFMLSNSPG--GLGFETAPFK 183

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  987 LTPDFLFVMGtsGKKtSPHFQKFQDICVKAYLALRHHTNLLIILFSMMLMTG-MPQLTS--KEDIEYIRDALTVGKNEED 1063
Cdd:cd05168  184 LTQEYVEVMG--GLE-SDMFRYFKTLMIQGFLALRKHADRIVLLVEIMQQGSkLPCFFGggEFTIEQLRERFKLNLTEEE 260

                        250       260       270
                 ....*....|....*....|....*....|.
gi 21237725 1064 AKKYFLDQIEVCRDKGWTVQFNWFLHLVLGI 1094
Cdd:cd05168  261 CAQFVDSLIDKSLNNWRTRQYDNFQYLTNGI 291
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
739-1085 2.59e-44

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 176.13  E-value: 2.59e-44
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  739 IEMLQKVtldIKSLSAEKYDVSSQVISQLKQKLENLQ----------NSQLP--ESFRVPYDPGLKAGALAIEK-----C 801
Cdd:COG5032 1699 IRKKFKI---DISLLNLSRKLYISVLRSIRKRLKRLLelrlkkvspkLLLFHafLEIKLPGQYLLDKPFVLIERfepevS 1775

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  802 KVMASKKKPLWLEFKCADptalsNETIGIIFKHGDDLRQDMLILQILRIMESIW----ETESLDLCLLPYGCISTGDKIG 877
Cdd:COG5032 1776 VVKSHLQRPRRLTIRGSD-----GKLYSFIVKGGDDLRQDELALQLIRLMNKILkkdkETRRRDLWIRPYKVIPLSPGSG 1850

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  878 MIEIVKDATTIAKI------------------QQSTVGNTGAFKDE-----------VLNHWLKEKSPTEEKFQAAVERF 928
Cdd:COG5032 1851 IIEWVPNSDTLHSIlreyhkrknisidqekklAARLDNLKLLLKDEfftkatlksppVLYDWFSESFPNPEDWLTARTNF 1930

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  929 VYSCAGYCVATFVLGIGDRHNDNIMITE-TGNLFHIDFGHILGNYKSFLGINkERVPFVLTPDFLFVMGTSGKKTSphfq 1007
Cdd:COG5032 1931 ARSLAVYSVIGYILGLGDRHPGNILIDRsSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAMGVSGVEGS---- 2005

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725 1008 kFQDICVKAYLALRHHTNLLIILFSMML------------MTGMPQLTSKEDIEYIRDALTvgknEEDAKKYFL----DQ 1071
Cdd:COG5032 2006 -FRELCETAFRALRKNADSLMNVLELFVrdpliewrrlpcFREIQNNEIVNVLERFRLKLS----EKDAEKFVDllinKS 2080

                        410
                 ....*....|....
gi 21237725 1072 IEVCRdKGWTVQFN 1085
Cdd:COG5032 2081 VESLI-TQATDPFQ 2093
C2_PI3K_like cd08380
C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes ...
 352-527 9.70e-42

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: 150.20  E-value: 9.70e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  352 VSLWDCDRKFRVKIRGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPK-PFTEEVLWNVWLEFSIKIKDLPKGALLN 430
Cdd:cd08380    1 KSLWDINFNLRIKIHGITNINLLDSEDLKLYVRVQLYHGGEPLCPPQSTKKvPFSTSVTWNEWLTFDILISDLPREARLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  431 LQIYCGKAPAlsskasaespssesKGKVQLLYYVNLLLIDHRFLLRRGEYVLHMWQISGKGEDQGsfnadklTSATNPDK 510
Cdd:cd08380   81 LSIYAVSEPG--------------SKKEVPLGWVNVPLFDYKGKLRQGMITLNLWPGKKTDPRIA-------CTPCNNSN 139

                        170
                 ....*....|....*..
gi 21237725  511 ENSMSISILLDNYCHPI 527
Cdd:cd08380  140 ENSTRLLIELPEFSKPV 156
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 203-312 2.17e-35

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


Pssm-ID: 197540  Cd Length: 108  Bit Score: 130.14  E-value: 2.17e-35
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725     203 TSKPLPEYLWKKIANNCIFIVIHRS--TTSQTIKVSPDDTPGAILQSFFTKMakkKSLMDIPESQSEqDFVLRVCGRDEY 280
Cdd:smart00144    1 TSPSVPEPLPLKTIANKILIVVHLEkdQQTKTLKVNPNCTPDSVLAQAFTKM---LSLHDQVDPTSE-DYILKVCGRDEY 76

                            90       100       110
                    ....*....|....*....|....*....|..
gi 21237725     281 LVGETPIKNFQWVRHCLKNGEEIHVVLDTPPD 312
Cdd:smart00144   77 LLGDHPLGSFEYIRNCLKNGTEPHLVLMTLSA 108
PI3Ka_III cd00870
Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is ...
 548-703 1.64e-32

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: 123.98  E-value: 1.64e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  548 PNQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLARrevWDQsaLDVGLT 627
Cdd:cd00870    7 NSKERKELNKILKYPPTTKLTDEEKDLIWKFRFYLTNNKKALTKFLKSVNWSDEQEVKQALELMPK---WAK--IDIEDA 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  628 MQLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYH-------DSALARFLLKRGLRNKRIGHFLFWFLR 700
Cdd:cd00870   82 LELLSPYFTNPVVRKYAVSRLKLASDEELLLYLLQLVQALKYENLDlsplprlDSPLADFLIERALKNPKLANFLYWYLK 161


                 ...
gi 21237725  701 SEI 703
Cdd:cd00870  162 VEL 164
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
 553-719 3.08e-31

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: 120.64  E-value: 3.08e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  553 KQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLARrevWdqSALDVGLTMQLLD 632
Cdd:cd00869    5 EKLLDLIQKQSTYTLSTEDKDLLWEKRLYCTNEPNALPLVLASAPSWDWANLMDVYQLLHQ---W--APLRPLIALELLL 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  633 CNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEIAQSrHYQQR 712
Cdd:cd00869   80 PKFPDQEVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALDDC-YFSSA 158


                 ....*..
gi 21237725  713 FAVILEA 719
Cdd:cd00869  159 YQDLGAA 165
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
 802-1035 5.82e-30

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: 118.91  E-value: 5.82e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  802 KVMASKKKPLWLEFKCadptalSNETIGI-IFKHGDDLRQDMLILQILRIMESIWETES----LDLCLLPYGCISTGDKI 876
Cdd:cd05164    9 RILASLQKPKKITILG------SDGKEYPfLVKGDDDLRKDERVMQLFQLLNTLLEKDKetrkRNLTIRTYSVVPLSSQS 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  877 GMIEIVKDATTiakiqqstvgntgaFKDeVLNHWLKEKSPTEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMI-T 955
Cdd:cd05164   83 GLIEWVDNTTT--------------LKP-VLKKWFNETFPDPTQWYEARSNYTKSTAVMSMVGYIIGLGDRHLENILIdT 147

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  956 ETGNLFHIDFGHILGNYKSFLgiNKERVPFVLTPDFLFVMGTSGKKTsphfqKFQDICVKAYLALRHHTNLLIILFSMML 1035
Cdd:cd05164  148 KTGEVVHIDFGMIFNKGKTLP--VPEIVPFRLTRNIINGMGPTGVEG-----LFRKSCEQVLRVFRKHKDKLITFLDTFL 220
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 203-312 2.71e-29

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


Pssm-ID: 395642  Cd Length: 106  Bit Score: 112.77  E-value: 2.71e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725    203 TSKPLPEYLwKKIANNCIFIVIH--RSTTSQTIKVSPDDTPGAILQSFFTKmakKKSLMDIPESQSeqDFVLRVCGRDEY 280
Cdd:pfam00794    1 ASTVSPEPL-PKLINNKLLISVHleGDQMTKTFTCNPNSTPGSLIAQALTK---KLSVHTQGDVTD--DYVLKVCGRDEY 74

                           90       100       110
                   ....*....|....*....|....*....|..
gi 21237725    281 LVGETPIKNFQWVRHCLKNGEEIHVVLDTPPD 312
Cdd:pfam00794   75 LLGDHPLGQFEYIRNCLKSGREPHLTLVEQSS 106
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 349-444 1.00e-27

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 107.82  E-value: 1.00e-27
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725     349 VFTVSLWDCDRKFRVKIRGIDIPVLPRNTDL-TVFVEANIQHGQQVLC-QRRTSPKPFTEEVLWNVWLEFSIKIKDLPKG 426
Cdd:smart00142    1 VKIESLWDCDRNLVITIALIHGIPLNWSRDYsDLYVEIQLYHGGKLLClPVSTSYKPFFPSVKWNEWLTFPIQISDLPRE 80

                            90
                    ....*....|....*...
gi 21237725     427 ALLNLQIYCGKAPALSSK 444
Cdd:smart00142   81 ARLCITIYAVKNPSKGSE 98
PIKKc_DNA-PK cd05172
Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, ...
 803-1028 9.11e-27

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: 109.97  E-value: 9.11e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  803 VMASKKKPLWLEFKCADptalsNETIGIIFKHGDDLRQDMLILQILRIMESIWETES----LDLCLLPYGCISTGDKIGM 878
Cdd:cd05172   10 VLSSKRRPKRITIRGSD-----EKEYKFLVKGGEDLRQDQRIQQLFDVMNNILASDPacrqRRLRIRTYQVIPMTSRLGL 84

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  879 IEIVKDATTIAKIqqstvgntgaFKDEVLNHWLKEKSPTEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMI-TET 957
Cdd:cd05172   85 IEWVDNTTPLKEI----------LENDLLRRALLSLASSPEAFLALRSNFARSLAAMSICGYILGIGDRHLSNFLVdLST 154

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 21237725  958 GNLFHIDFGHILGNYKSFLGInKERVPFVLTPDFLFVMGtsgkktsPHFQK--FQDICVKAYLALRHHTNLLI 1028
Cdd:cd05172  155 GRLIGIDFGHAFGSATQFLPI-PELVPFRLTRQLLNLLQ-------PLDARglLRSDMVHVLRALRAGRDLLL 219
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
 808-966 2.18e-23

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: 96.74  E-value: 2.18e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  808 KKPLWLEFKCadptalsnETIGIIFKHGDD--------LRQDMLILQILRIMEsiwetesldlcLLPYGCISTGD----K 875
Cdd:cd13968    7 AKVFWAEGEC--------TTIGVAVKIGDDvnneegedLESEMDILRRLKGLE-----------LNIPKVLVTEDvdgpN 67

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  876 IGMIEIVKDATTIAKIQqstvgntgafkdevlnhwlkekspTEEKFQAAVERFVYSCAGYCVATFV--LGIGDRHNDNIM 953
Cdd:cd13968   68 ILLMELVKGGTLIAYTQ------------------------EEELDEKDVESIMYQLAECMRLLHSfhLIHRDLNNDNIL 123

                        170
                 ....*....|...
gi 21237725  954 ITETGNLFHIDFG 966
Cdd:cd13968  124 LSEDGNVKLIDFG 136
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 799-1034 1.32e-21

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: 94.88  E-value: 1.32e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  799 EKCKVMASKKKPLWLEFKCADptalsNETIGIIFKHGDDLRQDM----LILQILRIMESIWETESLDLCLLPYGCISTGD 874
Cdd:cd00892    6 DEVEIMPSLQKPKKITLVGSD-----GKKYPFLCKPKDDLRKDArmmeFNTLINRLLSKDPESRRRNLHIRTYAVIPLNE 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  875 KIGMIEIVKDATTIAKIQQStvgntgaFKDEVLNHWLKEKSPTEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMI 954
Cdd:cd00892   81 ECGIIEWVPNTVTLRSILST-------LYPPVLHEWFLKNFPDPTAWYEARNNYTRSTAVMSMVGYILGLGDRHGENILF 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  955 -TETGNLFHIDFGHILGNYKSfLGInKERVPFVLTPDFLFVMGTSGKKTSphfqkFQDICVKAYLALRHHTNLLI-ILFS 1032
Cdd:cd00892  154 dSTTGDVVHVDFDCLFDKGLT-LEV-PERVPFRLTQNMVDAMGVTGVEGT-----FRRTCEVTLRVLRENRETLMsVLET 226


                 ..
gi 21237725 1033 MM 1034
Cdd:cd00892  227 FV 228
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 352-523 3.73e-19

C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. The members here are class I, beta and delta isoforms of PI3Ks and contain both a Ras-binding domain and a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members have a type-I topology.


Pssm-ID: 176075  Cd Length: 173  Bit Score: 85.83  E-value: 3.73e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  352 VSLWDCDRKFRVKIRGIDiPVLPRNTDLTVFVEANIQHGQQVLC-QRRTSPKPFTEEVLWNVWLEFSIKIKDLPKGALLN 430
Cdd:cd08693    1 KSLWDIEEKFSITLHKIS-NLNAAERTMKVGVQAGLFHGGESLCkTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLC 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  431 LQIY--CGKAPALSSKasaespSSESKGKVQLLYY----VNLLLIDHRFLLRRGEYVLHMWQISgkgEDQGSFNADKL-T 503
Cdd:cd08693   80 FAIYevSKKAKGKRSR------KNQTKKKKKKDDNpiawVNTMVFDYKGQLKTGDHTLYMWTYA---EDQSEDLLNPLgT 150

                        170       180
                 ....*....|....*....|
gi 21237725  504 SATNPDKENSMSISILLDNY 523
Cdd:cd08693  151 VESNPNTESATALHISFPEY 170
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
 831-1030 3.38e-16

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: 80.28  E-value: 3.38e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  831 IFKHGDDLRQDMLILQILRIMESIW----ETESLDLCLLPYGCISTGDKIGMIEIVKDATTIAKIQQSTVGNTGA----F 902
Cdd:cd05171   33 LVKGGDDLRQDAVMEQVFELVNQLLkrdkETRKRKLRIRTYKVVPLSPRSGVLEFVENTIPLGEYLVGASSKSGAharyR 112

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  903 KDEVLNH------WLKEKSPTEEKFQAAVE---------RFV----YSCAG--------YC--VAT-----FVLGIGDRH 948
Cdd:cd05171  113 PKDWTAStcrkkmREKAKASAEERLKVFDEicknfkpvfRHFflekFPDPSdwferrlaYTrsVATssivgYILGLGDRH 192

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  949 NDNIMI-TETGNLFHIDFGHILGNYKsFLGInKERVPFVLTPDFLFVMGTSGKKTSphfqkFQDICVKAYLALR-HHTNL 1026
Cdd:cd05171  193 LNNILIdQKTGELVHIDLGIAFEQGK-LLPI-PETVPFRLTRDIVDGMGITGVEGV-----FRRCCEETLRVLReNKEAL 265


                 ....
gi 21237725 1027 LIIL 1030
Cdd:cd05171  266 LTIL 269
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 802-988 8.71e-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: 67.12  E-value: 8.71e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  802 KVMASKKKPLWLEFKCADptalsnetiGIIFK-----HgDDLRQDMLILQILR----IMESIWETESLDLCLLPYGCIST 872
Cdd:cd05169    9 EVITSKQRPRKLTIVGSD---------GKEYKfllkgH-EDLRLDERVMQLFGlvntLLKNDSETSRRNLSIQRYSVIPL 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  873 GDKIGMIEIVKDATTIAKI---------------QQSTVGNTGAF-------KDEVLNH--------------WLKekSP 916
Cdd:cd05169   79 SPNSGLIGWVPGCDTLHSLirdyrekrkiplnieHRLMLQMAPDYdnltliqKVEVFEYalentpgddlrrvlWLK--SP 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  917 TEEKFqaaVER---FVYSCAGYCVATFVLGIGDRHNDNIMI-TETGNLFHIDFGhilgnyKSF-LGINK----ERVPFVL 987
Cdd:cd05169  157 SSEAW---LERrtnFTRSLAVMSMVGYILGLGDRHPSNIMLdRLTGKVIHIDFG------DCFeVAMHRekfpEKVPFRL 227


                 .
gi 21237725  988 T 988
Cdd:cd05169  228 T 228
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 381-486 1.04e-09

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: 57.76  E-value: 1.04e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725    381 VFVEANIQHGQQVLCQR-RTSPKPF-TEEVLWNVWLEFSIKIKDLPKGALLNLQIYCGKAPalsskasaespssesKGKV 458
Cdd:pfam00792    5 LYVECQLYHGGKPLCLPvSTRYVPFsNSSIKWNEWITFPIQISDLPRSARLCITIWDVSGP---------------EKSF 69

                           90       100
                   ....*....|....*....|....*...
gi 21237725    459 QLLYYVNLLLIDHRFLLRRGEYVLHMWQ 486
Cdd:pfam00792   70 VPIGWVNTSLFDKKGILRQGKQKLRLWP 97
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
 832-1033 4.34e-09

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: 59.19  E-value: 4.34e-09
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  832 FKHGDDLRQDMLILQILRI----MESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTI-----------AKIQQSTV 896
Cdd:cd05170   34 FKGLEDLHLDERIMQFLSIvnamLASDNEHRRRRYRARHYSVTPLGPRSGLIQWVDGATPLfslykrwqqrrAAAQAQKN 113

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  897 GNTGAFKDEVL-------------------------NHW----LKE--------------------KSPTEEKFQAAVER 927
Cdd:cd05170  114 QDSGSTPPPVPrpselfynklkpalkaagirkstsrREWplevLRQvleelvaetprdllarelwcSSPSSAEWWRVTQR 193

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  928 FVYSCAGYCVATFVLGIGDRHNDNIMIT-ETGNLFHIDF------GHILgnyksflginK--ERVPFVLTPDF---LFVM 995
Cdd:cd05170  194 FARSLAVMSMIGYIIGLGDRHLDNILVDlSTGEVVHIDYnvcfekGKRL----------RvpEKVPFRLTQNIehaLGPT 263

                        250       260       270
                 ....*....|....*....|....*....|....*...
gi 21237725  996 GTSGkktsphfqKFQDICVKAYLALRHHTNLLIILFSM 1033
Cdd:cd05170  264 GVEG--------TFRLSCEQVLKILRKGRETLLTLLEA 293
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 382-485 2.63e-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: 54.67  E-value: 2.63e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  382 FVEANIQHGQQVLCQRRTSP-----KPFTEEVLWNVWLEFSIKIKDLPKGALLNLQIYCGKAPALSSkasaesPSSESKG 456
Cdd:cd04012   32 YLSCSLYHGGRLLCSPVTTKpvkitKSFFPRVVWDEWIEFPIPVCQLPRESRLVLTLYGTTSSPDGG------SNKQRMG 105

                         90       100
                 ....*....|....*....|....*....
gi 21237725  457 KVQlLYYVNLLLIDHRFLLRRGEYVLHMW 485
Cdd:cd04012  106 PEE-LGWVSLPLFDFRGVLRQGSLLLGLW 133
C2_PI3K_class_I_alpha cd08398
C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 353-527 3.14e-08

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: 54.03  E-value: 3.14e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  353 SLWDCDRKFRVKIR-GIDIPVLPRNTdltVFVEANIQHGQQVLCQRRTSPKPFTEEVLWNVWLEFSIKIKDLPKGALLNL 431
Cdd:cd08398    2 SLWKINSNLRIKILcATYVNVNDIDK---IYVRTGIYHGGEPLCDNVNTQRVPCSNPRWNEWLDYDIYIPDLPRSARLCL 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  432 QIycgkapaLSSKasaespssESKGKVQ---LLYYVNLLLIDHRFLLRRGEYVLHMWQISGKGEDQgsFNADKLTsATNP 508
Cdd:cd08398   79 SI-------CSVK--------GRKGAKEehcPLAWGNINLFDYTDTLVSGKMALNLWPVPHGLEDL--LNPIGVT-GSNP 140

                        170
                 ....*....|....*....
gi 21237725  509 DKEnSMSISILLDNYCHPI 527
Cdd:cd08398  141 NKD-TPCLELEFDRFSCVV 158
C2_PI3K_class_III cd08397
C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 375-434 4.41e-06

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: 48.01  E-value: 4.41e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 21237725  375 RNTDLtvFVEANIQHGQQVLC-QRRTSPKPFTEEVLWNVWLEFSIKIKDLPKGALLNLQIY 434
Cdd:cd08397   28 PNSDL--FVTCQVFDDGKPLTlPVQTSYKPFKNRRNWNEWLTLPIKYSDLPRNSQLAITIW 86
PIKK_TRRAP cd05163
Pseudokinase domain of TRansformation/tRanscription domain-Associated Protein; TRRAP belongs ...
 891-999 5.93e-04

Pseudokinase domain of TRansformation/tRanscription domain-Associated Protein; TRRAP belongs to the the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. It contains a FATC (FRAP, ATM and TRRAP, C-terminal) domain and has a large molecular weight. Unlike most PIKK proteins, however, it contains an inactive PI3K-like pseudokinase domain, which lacks the conserved residues necessary for ATP binding and catalytic activity. TRRAP also contains many motifs that may be critical for protein-protein interactions. TRRAP is a common component of many histone acetyltransferase (HAT) complexes, and is responsible for the recruitment of these complexes to chromatin during transcription, replication, and DNA repair. TRRAP also exists in non-HAT complexes such as the p400 and MRN complexes, which are implicated in ATP-dependent remodeling and DNA repair, respectively. The TRRAP pseudokinase 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: 270707  Cd Length: 252  Bit Score: 42.89  E-value: 5.93e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21237725  891 IQQSTVGNTgafkdeVLNHWLKEKSPTEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITE-TGNLFHIDFGHIL 969
Cdd:cd05163  110 IQSKMVPET------ILSNYFLRTMPSPSDLWLFRKQFTLQLALSSFMTYVLSLGNRTPHRILISRsTGNVFMTDFLPSI 183

                         90       100       110
                 ....*....|....*....|....*....|...
gi 21237725  970 GNYKSFLGINkERVPFVLTPD---FLFVMGTSG 999
Cdd:cd05163  184 NSQGPLLDNN-EPVPFRLTPNiqhFIGPIGVEG 215
 
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.
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