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Conserved domains on  [gi|767948061|ref|XP_011514619|]
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phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X4 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
C2_PI3K_class_I_gamma cd08399
C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 350-527 2.66e-114

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: 346.51  E-value: 2.66e-114
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 350 FTVSLWDCDRKFRVKIRGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFTEEVLWNVWLEFSIKIKDLPKGALL 429
Cdd:cd08399    1 FTVSLWDCDRKFRVKILGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFTEEVLWNTWLEFDIKIKDLPKGALL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 430 NLQIYCGKAPALSSKASAESPSSESKGKVQLLYYVNLLLIDHRFLLRRGEYVLHMWQISGKGEDQGSFNADKLTSATNPD 509
Cdd:cd08399   81 NLQIYCGKAPALSSKKSAESPSSESKGKHQLLYYVNLLLIDHRFLLRTGEYVLHMWQISGKGEDQGSVNADKLTSATNPD 160

                        170
                 ....*....|....*...
gi 767948061 510 KENSMSISILLDNYCHPI 527
Cdd:cd08399  161 KENSMSISILLDNYCHPV 178
PIK3CG_ABD pfam19710
PIK3 catalytic subunit gamma adaptor-binding domain; This is the N-terminal domain from ...
 1-192 5.48e-114

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: 345.98  E-value: 5.48e-114
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061    1 MELENYKQPVVLREDNCRRRRRMKPRSAAASLSSMELIPIEFVLPTSQRKCKSPETALLHVAGHGNVEQMKAQVWLRALE 80
Cdd:pfam19710   4 MQLSDHEQPVVMREENRRRRRRMKKAFTSASSSSMELISIEFVLPTSNKNTKTPDTLLLEVAGNWTVEQVKAQVWLRAVE 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061   81 TSVAADFYHRLGPHHFLLLYQKKGQWYEIYDKYQVVQTLDCLRYWKATHRSPGQIHLVQRHPPSEESQAFQRQLTALIGY 160
Cdd:pfam19710  84 TNLCPDFYQKFSPDQFILLYQKKGQWYEIYDKHQVFQTLDCIRYWKALQKDVGKIHLVQRPQPSEESLQYQRQLNYLIGY 163

                         170       180       190
                  ....*....|....*....|....*....|..
gi 767948061  161 DVTDVSNVHDDELEFTRRGLVTPRMAEVASRD 192
Cdd:pfam19710 164 DVTDVSNVHDDELEFTRRKLVTPRMIELSDRD 195
PKc_like super family cl21453
Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the ...
 729-876 2.30e-93

Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the catalytic domains of serine/threonine-specific and tyrosine-specific protein kinases. It also includes RIO kinases, which are atypical serine protein kinases, aminoglycoside phosphotransferases, and choline kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to hydroxyl groups in specific substrates such as serine, threonine, or tyrosine residues of proteins.


The actual alignment was detected with superfamily member cd00894:

Pssm-ID: 473864 [Multi-domain]  Cd Length: 367  Bit Score: 298.70  E-value: 2.30e-93
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 729 LHDFTQQVQVIEMLQKVTLDIKSLSAEKYDVSSQVISQLKQKLENLQNSQLPESFRVPYDPGLKAGALAIEKCKVMASKK 808
Cdd:cd00894    1 LHDFTQQVQVIEMLQKVTLDIKSLSAEKYDVSSQVISQLKQKLENLQNSQLPESFRVPYDPGLRAGALVIEKCKVMASKK 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767948061 809 KPLWLEFKCADPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKI 876
Cdd:cd00894   81 KPLWLEFKCADPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKI 148
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 549-725 1.76e-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: 280.74  E-value: 1.76e-89
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 549 NQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLARRevwdqSALDVGLTM 628
Cdd:cd00872    1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRKKPQALPKLLLSVKWNKRDDVAQMYQLLKRW-----PKLKPEQAL 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 629 QLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEIAQSRH 708
Cdd:cd00872   76 ELLDCNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSV 155

                        170
                 ....*....|....*..
gi 767948061 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 1.85e-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: 1.85e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061   203 TSKPLPEYLWKKIANNCIFIVIHRS--TTSQTIKVSPDDTPGAILQSFFTKMakkKSLMDIPESQSEqDFVLRVCGRDEY 280
Cdd:smart00144   1 TSPSVPEPLPLKTIANKILIVVHLEkdQQTKTLKVNPNCTPDSVLAQAFTKM---LSLHDQVDPTSE-DYILKVCGRDEY 76

                           90       100       110
                   ....*....|....*....|....*....|..
gi 767948061   281 LVGETPIKNFQWVRHCLKNGEEIHVVLDTPPD 312
Cdd:smart00144  77 LLGDHPLGSFEYIRNCLKNGTEPHLVLMTLSA 108
 
Name Accession Description Interval E-value
C2_PI3K_class_I_gamma cd08399
C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 350-527 2.66e-114

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: 346.51  E-value: 2.66e-114
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 350 FTVSLWDCDRKFRVKIRGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFTEEVLWNVWLEFSIKIKDLPKGALL 429
Cdd:cd08399    1 FTVSLWDCDRKFRVKILGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFTEEVLWNTWLEFDIKIKDLPKGALL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 430 NLQIYCGKAPALSSKASAESPSSESKGKVQLLYYVNLLLIDHRFLLRRGEYVLHMWQISGKGEDQGSFNADKLTSATNPD 509
Cdd:cd08399   81 NLQIYCGKAPALSSKKSAESPSSESKGKHQLLYYVNLLLIDHRFLLRTGEYVLHMWQISGKGEDQGSVNADKLTSATNPD 160

                        170
                 ....*....|....*...
gi 767948061 510 KENSMSISILLDNYCHPI 527
Cdd:cd08399  161 KENSMSISILLDNYCHPV 178
PIK3CG_ABD pfam19710
PIK3 catalytic subunit gamma adaptor-binding domain; This is the N-terminal domain from ...
 1-192 5.48e-114

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: 345.98  E-value: 5.48e-114
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061    1 MELENYKQPVVLREDNCRRRRRMKPRSAAASLSSMELIPIEFVLPTSQRKCKSPETALLHVAGHGNVEQMKAQVWLRALE 80
Cdd:pfam19710   4 MQLSDHEQPVVMREENRRRRRRMKKAFTSASSSSMELISIEFVLPTSNKNTKTPDTLLLEVAGNWTVEQVKAQVWLRAVE 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061   81 TSVAADFYHRLGPHHFLLLYQKKGQWYEIYDKYQVVQTLDCLRYWKATHRSPGQIHLVQRHPPSEESQAFQRQLTALIGY 160
Cdd:pfam19710  84 TNLCPDFYQKFSPDQFILLYQKKGQWYEIYDKHQVFQTLDCIRYWKALQKDVGKIHLVQRPQPSEESLQYQRQLNYLIGY 163

                         170       180       190
                  ....*....|....*....|....*....|..
gi 767948061  161 DVTDVSNVHDDELEFTRRGLVTPRMAEVASRD 192
Cdd:pfam19710 164 DVTDVSNVHDDELEFTRRKLVTPRMIELSDRD 195
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 729-876 2.30e-93

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: 298.70  E-value: 2.30e-93
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 729 LHDFTQQVQVIEMLQKVTLDIKSLSAEKYDVSSQVISQLKQKLENLQNSQLPESFRVPYDPGLKAGALAIEKCKVMASKK 808
Cdd:cd00894    1 LHDFTQQVQVIEMLQKVTLDIKSLSAEKYDVSSQVISQLKQKLENLQNSQLPESFRVPYDPGLRAGALVIEKCKVMASKK 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767948061 809 KPLWLEFKCADPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKI 876
Cdd:cd00894   81 KPLWLEFKCADPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKI 148
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 549-725 1.76e-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: 280.74  E-value: 1.76e-89
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 549 NQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLARRevwdqSALDVGLTM 628
Cdd:cd00872    1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRKKPQALPKLLLSVKWNKRDDVAQMYQLLKRW-----PKLKPEQAL 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 629 QLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEIAQSRH 708
Cdd:cd00872   76 ELLDCNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSV 155

                        170
                 ....*....|....*..
gi 767948061 709 yQQRFAVILEAYLRGCG 725
Cdd:cd00872  156 -SQRFGLLLEAYLRGCG 171
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 543-733 5.14e-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: 251.10  E-value: 5.14e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061  543 VRAEMPNQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLARrevWDQsaL 622
Cdd:pfam00613   1 KDLKPNEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYLMLVPKALTKLLLSVKWSDLSEVAEALSLLLK---WAP--I 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061  623 DVGLTMQLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSE 702
Cdd:pfam00613  76 DPVDALELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSE 155

                         170       180       190
                  ....*....|....*....|....*....|.
gi 767948061  703 IaQSRHYQQRFAVILEAYLRGCGTAMLHDFT 733
Cdd:pfam00613 156 I-HDEEVSPRFGSLLELYLRSCGTSLLGLNK 185
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 545-732 2.77e-73

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: 238.31  E-value: 2.77e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061   545 AEMPNQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLK-HPKAYPKLFSSVKWGQQEIVAKTYQLLARrevWDqsALD 623
Cdd:smart00145   1 KPLDIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTnNPKALPKFLLSVKWSDADEVAQALSLLLS---WA--PLD 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061   624 VGLTMQLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEI 703
Cdd:smart00145  76 PEDALELLDPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSEL 155

                          170       180
                   ....*....|....*....|....*....
gi 767948061   704 aQSRHYQQRFAVILEAYLRGCGTAMLHDF 732
Cdd:smart00145 156 -HDPHVSIRFGLLLEAYLRGCGTHLKELL 183
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 203-312 1.85e-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: 1.85e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061   203 TSKPLPEYLWKKIANNCIFIVIHRS--TTSQTIKVSPDDTPGAILQSFFTKMakkKSLMDIPESQSEqDFVLRVCGRDEY 280
Cdd:smart00144   1 TSPSVPEPLPLKTIANKILIVVHLEkdQQTKTLKVNPNCTPDSVLAQAFTKM---LSLHDQVDPTSE-DYILKVCGRDEY 76

                           90       100       110
                   ....*....|....*....|....*....|..
gi 767948061   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 3.02e-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: 112.39  E-value: 3.02e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061  203 TSKPLPEYLwKKIANNCIFIVIH--RSTTSQTIKVSPDDTPGAILQSFFTKmakKKSLMDIPESQSeqDFVLRVCGRDEY 280
Cdd:pfam00794   1 ASTVSPEPL-PKLINNKLLISVHleGDQMTKTFTCNPNSTPGSLIAQALTK---KLSVHTQGDVTD--DYVLKVCGRDEY 74

                          90       100       110
                  ....*....|....*....|....*....|..
gi 767948061  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 1.02e-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: 1.02e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061   349 VFTVSLWDCDRKFRVKIRGIDIPVLPRNTDL-TVFVEANIQHGQQVLC-QRRTSPKPFTEEVLWNVWLEFSIKIKDLPKG 426
Cdd:smart00142   1 VKIESLWDCDRNLVITIALIHGIPLNWSRDYsDLYVEIQLYHGGKLLClPVSTSYKPFFPSVKWNEWLTFPIQISDLPRE 80

                           90
                   ....*....|....*...
gi 767948061   427 ALLNLQIYCGKAPALSSK 444
Cdd:smart00142  81 ARLCITIYAVKNPSKGSE 98
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 830-876 3.50e-13

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: 70.02  E-value: 3.50e-13
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 767948061   830 IIFKHGDDLRQDMLILQILRIMESIWETES----LDLCLLPYGCISTGDKI 876
Cdd:smart00146   1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDKetrrRDLHLRPYKVIPTGPKS 51
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 828-875 3.01e-12

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: 67.35  E-value: 3.01e-12
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 767948061  828 IGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLL-PYGCISTGDK 875
Cdd:pfam00454   2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLRRLkPYSVIPLGPK 50
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 381-486 9.09e-10

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: 9.09e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061  381 VFVEANIQHGQQVLCQR-RTSPKPF-TEEVLWNVWLEFSIKIKDLPKGALLNLQIYCGKAPalsskasaespssesKGKV 458
Cdd:pfam00792   5 LYVECQLYHGGKPLCLPvSTRYVPFsNSSIKWNEWITFPIQISDLPRSARLCITIWDVSGP---------------EKSF 69

                          90       100
                  ....*....|....*....|....*...
gi 767948061  459 QLLYYVNLLLIDHRFLLRRGEYVLHMWQ 486
Cdd:pfam00792  70 VPIGWVNTSLFDKKGILRQGKQKLRLWP 97
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
739-877 3.86e-08

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 57.49  E-value: 3.86e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061  739 IEMLQKVtldIKSLSAEKYDVSSQVISQLKQKLENLQ----------NSQLP--ESFRVPYDPGLKAGALAIEK-----C 801
Cdd:COG5032  1699 IRKKFKI---DISLLNLSRKLYISVLRSIRKRLKRLLelrlkkvspkLLLFHafLEIKLPGQYLLDKPFVLIERfepevS 1775

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061  802 KVMASKKKPLWLEFKCADptalsNETIGIIFKHGDDLRQDMLILQILRIMESIW----ETESLDLCLLPYGCISTGDKID 877
Cdd:COG5032  1776 VVKSHLQRPRRLTIRGSD-----GKLYSFIVKGGDDLRQDELALQLIRLMNKILkkdkETRRRDLWIRPYKVIPLSPGSG 1850
 
Name Accession Description Interval E-value
C2_PI3K_class_I_gamma cd08399
C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 350-527 2.66e-114

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: 346.51  E-value: 2.66e-114
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 350 FTVSLWDCDRKFRVKIRGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFTEEVLWNVWLEFSIKIKDLPKGALL 429
Cdd:cd08399    1 FTVSLWDCDRKFRVKILGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFTEEVLWNTWLEFDIKIKDLPKGALL 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 430 NLQIYCGKAPALSSKASAESPSSESKGKVQLLYYVNLLLIDHRFLLRRGEYVLHMWQISGKGEDQGSFNADKLTSATNPD 509
Cdd:cd08399   81 NLQIYCGKAPALSSKKSAESPSSESKGKHQLLYYVNLLLIDHRFLLRTGEYVLHMWQISGKGEDQGSVNADKLTSATNPD 160

                        170
                 ....*....|....*...
gi 767948061 510 KENSMSISILLDNYCHPI 527
Cdd:cd08399  161 KENSMSISILLDNYCHPV 178
PIK3CG_ABD pfam19710
PIK3 catalytic subunit gamma adaptor-binding domain; This is the N-terminal domain from ...
 1-192 5.48e-114

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: 345.98  E-value: 5.48e-114
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061    1 MELENYKQPVVLREDNCRRRRRMKPRSAAASLSSMELIPIEFVLPTSQRKCKSPETALLHVAGHGNVEQMKAQVWLRALE 80
Cdd:pfam19710   4 MQLSDHEQPVVMREENRRRRRRMKKAFTSASSSSMELISIEFVLPTSNKNTKTPDTLLLEVAGNWTVEQVKAQVWLRAVE 83

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061   81 TSVAADFYHRLGPHHFLLLYQKKGQWYEIYDKYQVVQTLDCLRYWKATHRSPGQIHLVQRHPPSEESQAFQRQLTALIGY 160
Cdd:pfam19710  84 TNLCPDFYQKFSPDQFILLYQKKGQWYEIYDKHQVFQTLDCIRYWKALQKDVGKIHLVQRPQPSEESLQYQRQLNYLIGY 163

                         170       180       190
                  ....*....|....*....|....*....|..
gi 767948061  161 DVTDVSNVHDDELEFTRRGLVTPRMAEVASRD 192
Cdd:pfam19710 164 DVTDVSNVHDDELEFTRRKLVTPRMIELSDRD 195
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 729-876 2.30e-93

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: 298.70  E-value: 2.30e-93
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 729 LHDFTQQVQVIEMLQKVTLDIKSLSAEKYDVSSQVISQLKQKLENLQNSQLPESFRVPYDPGLKAGALAIEKCKVMASKK 808
Cdd:cd00894    1 LHDFTQQVQVIEMLQKVTLDIKSLSAEKYDVSSQVISQLKQKLENLQNSQLPESFRVPYDPGLRAGALVIEKCKVMASKK 80

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767948061 809 KPLWLEFKCADPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKI 876
Cdd:cd00894   81 KPLWLEFKCADPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKI 148
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 549-725 1.76e-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: 280.74  E-value: 1.76e-89
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 549 NQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLARRevwdqSALDVGLTM 628
Cdd:cd00872    1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRKKPQALPKLLLSVKWNKRDDVAQMYQLLKRW-----PKLKPEQAL 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 629 QLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEIAQSRH 708
Cdd:cd00872   76 ELLDCNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSV 155

                        170
                 ....*....|....*..
gi 767948061 709 yQQRFAVILEAYLRGCG 725
Cdd:cd00872  156 -SQRFGLLLEAYLRGCG 171
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 543-733 5.14e-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: 251.10  E-value: 5.14e-78
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061  543 VRAEMPNQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLARrevWDQsaL 622
Cdd:pfam00613   1 KDLKPNEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYLMLVPKALTKLLLSVKWSDLSEVAEALSLLLK---WAP--I 75

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061  623 DVGLTMQLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSE 702
Cdd:pfam00613  76 DPVDALELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSE 155

                         170       180       190
                  ....*....|....*....|....*....|.
gi 767948061  703 IaQSRHYQQRFAVILEAYLRGCGTAMLHDFT 733
Cdd:pfam00613 156 I-HDEEVSPRFGSLLELYLRSCGTSLLGLNK 185
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 545-732 2.77e-73

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: 238.31  E-value: 2.77e-73
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061   545 AEMPNQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLK-HPKAYPKLFSSVKWGQQEIVAKTYQLLARrevWDqsALD 623
Cdd:smart00145   1 KPLDIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTnNPKALPKFLLSVKWSDADEVAQALSLLLS---WA--PLD 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061   624 VGLTMQLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEI 703
Cdd:smart00145  76 PEDALELLDPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSEL 155

                          170       180
                   ....*....|....*....|....*....
gi 767948061   704 aQSRHYQQRFAVILEAYLRGCGTAMLHDF 732
Cdd:smart00145 156 -HDPHVSIRFGLLLEAYLRGCGTHLKELL 183
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 729-876 2.50e-63

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: 217.89  E-value: 2.50e-63
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 729 LHDFTQQVQVIEMLQKVTLDIKSLSAEKydvsSQVISQLKQKLENLQNSQLPESFRVPYDPGLKAGALAIEKCKVMASKK 808
Cdd:cd05165    1 LKSLSRQVEALNKLKKLSDILKEKKKSK----EKVKKLLKECLKQKFYDEALQNFQSPLNPSHKLGELIIEKCKVMDSKK 76

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 767948061 809 KPLWLEFKCADPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKI 876
Cdd:cd05165   77 RPLWLVFENADPLALSGEDIKIIFKNGDDLRQDMLTLQIIRIMDNIWKEEGLDLRMLPYGCLSTGDNV 144
PI3Ka cd00864
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 549-703 1.65e-58

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: 196.67  E-value: 1.65e-58
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 549 NQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLARREvwdqsALDVGLTM 628
Cdd:cd00864    1 AWERKPLLAILLYPPFSTLTEEEKELLWKFRYYLLNVPKALPKLLKSVNWNDDEEVSELYQLLKWWA-----PLSPEDAL 75

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767948061 629 QLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEI 703
Cdd:cd00864   76 ELLSPKYPDPVVRQYAVRVLESASDDELLLYLPQLVQALKYEPYLDSYLARFLLERALKSQRLGHQLYWNLKSEI 150
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 730-876 2.56e-54

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: 191.63  E-value: 2.56e-54
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 730 HDFTQQVQVIEMLQKVTLDIKSLSAEKydvssqVISQLKQKLENLQnsqLPESFRVPYDPGLKAGALAIEKCKVMASKKK 809
Cdd:cd00891    2 EELLKQVKVLDELKEIAKKIKEEPSEE------RKEVLEKLLQKLE---LPKKFTLPLDPRMEVKGLIVEKCKVMDSKKL 72

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767948061 810 PLWLEFKCADPTAlsnETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKI 876
Cdd:cd00891   73 PLWLVFKNADPGG---DPIKVIFKAGDDLRQDQLTLQLLRIMDKLWKKEGLDLRMTPYKCIATGDEV 136
C2_PI3K_like cd08380
C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes ...
 352-527 5.49e-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: 150.59  E-value: 5.49e-42
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 352 VSLWDCDRKFRVKIRGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPK-PFTEEVLWNVWLEFSIKIKDLPKGALLN 430
Cdd:cd08380    1 KSLWDINFNLRIKIHGITNINLLDSEDLKLYVRVQLYHGGEPLCPPQSTKKvPFSTSVTWNEWLTFDILISDLPREARLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 431 LQIYCGKAPAlsskasaespssesKGKVQLLYYVNLLLIDHRFLLRRGEYVLHMWQISGKGEDQGsfnadklTSATNPDK 510
Cdd:cd08380   81 LSIYAVSEPG--------------SKKEVPLGWVNVPLFDYKGKLRQGMITLNLWPGKKTDPRIA-------CTPCNNSN 139

                        170
                 ....*....|....*..
gi 767948061 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 1.85e-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: 1.85e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061   203 TSKPLPEYLWKKIANNCIFIVIHRS--TTSQTIKVSPDDTPGAILQSFFTKMakkKSLMDIPESQSEqDFVLRVCGRDEY 280
Cdd:smart00144   1 TSPSVPEPLPLKTIANKILIVVHLEkdQQTKTLKVNPNCTPDSVLAQAFTKM---LSLHDQVDPTSE-DYILKVCGRDEY 76

                           90       100       110
                   ....*....|....*....|....*....|..
gi 767948061   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 4.10e-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: 122.82  E-value: 4.10e-32
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 548 PNQLRKQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLARrevWDQsaLDVGLT 627
Cdd:cd00870    7 NSKERKELNKILKYPPTTKLTDEEKDLIWKFRFYLTNNKKALTKFLKSVNWSDEQEVKQALELMPK---WAK--IDIEDA 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 628 MQLLDCNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYH-------DSALARFLLKRGLRNKRIGHFLFWFLR 700
Cdd:cd00870   82 LELLSPYFTNPVVRKYAVSRLKLASDEELLLYLLQLVQALKYENLDlsplprlDSPLADFLIERALKNPKLANFLYWYLK 161


                 ...
gi 767948061 701 SEI 703
Cdd:cd00870  162 VEL 164
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 730-875 1.95e-31

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: 126.64  E-value: 1.95e-31
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 730 HDFTQQVQVIEMLQKVTLDIKSLSaekydvSSQVISQLKQKLENLQNSQLPESFRVPYDPGLKAGALAIEKCKVMASKKK 809
Cdd:cd05166    2 EEFLKQHVLVQALTSIAEKVKSAK------DSARENALRRELEQLASFLLENSFRLPLDPALEVTGVDVRSCSYFNSNAL 75

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 767948061 810 PLWLEFKCADPTAlsnETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDK 875
Cdd:cd05166   76 PLKLVFRNADPRA---EPISVIFKVGDDLRQDMLTLQLIRIMDKIWLQEGLDLKMITFRCVPTGNK 138
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
 553-719 1.36e-30

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: 118.33  E-value: 1.36e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 553 KQLEAIIATDPLNPLTAEDKELLWHFRYESLKHPKAYPKLFSSVKWGQQEIVAKTYQLLARrevWdqSALDVGLTMQLLD 632
Cdd:cd00869    5 EKLLDLIQKQSTYTLSTEDKDLLWEKRLYCTNEPNALPLVLASAPSWDWANLMDVYQLLHQ---W--APLRPLIALELLL 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 633 CNFSDENVRAIAVQKLESLEDDDVLHYLLQLVQAVKFEPYHDSALARFLLKRGLRNKRIGHFLFWFLRSEIAQSrHYQQR 712
Cdd:cd00869   80 PKFPDQEVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALDDC-YFSSA 158


                 ....*..
gi 767948061 713 FAVILEA 719
Cdd:cd00869  159 YQDLGAA 165
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 203-312 3.02e-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: 112.39  E-value: 3.02e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061  203 TSKPLPEYLwKKIANNCIFIVIH--RSTTSQTIKVSPDDTPGAILQSFFTKmakKKSLMDIPESQSeqDFVLRVCGRDEY 280
Cdd:pfam00794   1 ASTVSPEPL-PKLINNKLLISVHleGDQMTKTFTCNPNSTPGSLIAQALTK---KLSVHTQGDVTD--DYVLKVCGRDEY 74

                          90       100       110
                  ....*....|....*....|....*....|..
gi 767948061  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 1.02e-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: 1.02e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061   349 VFTVSLWDCDRKFRVKIRGIDIPVLPRNTDL-TVFVEANIQHGQQVLC-QRRTSPKPFTEEVLWNVWLEFSIKIKDLPKG 426
Cdd:smart00142   1 VKIESLWDCDRNLVITIALIHGIPLNWSRDYsDLYVEIQLYHGGKLLClPVSTSYKPFFPSVKWNEWLTFPIQISDLPRE 80

                           90
                   ....*....|....*...
gi 767948061   427 ALLNLQIYCGKAPALSSK 444
Cdd:smart00142  81 ARLCITIYAVKNPSKGSE 98
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 724-874 8.76e-27

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: 113.23  E-value: 8.76e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 724 CGTAMLHdFTQQVQVIEMLQKVTlDIksLSAEKYDVSSQVisQLKQKLENLQNSQLPES---FRVPYDPGLKAGALAIEK 800
Cdd:cd05175    1 CGMYLKH-LSRQVEAMEKLINLT-DI--LKQEKKDETQKV--QMKFLVEQMRRPDFMDAlqgFLSPLNPAHQLGNLRLEE 74

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 767948061 801 CKVMASKKKPLWLEFKCAD-PTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGD 874
Cdd:cd05175   75 CRIMSSAKRPLWLNWENPDiMSELLFQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGD 149
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 732-875 2.76e-26

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: 111.59  E-value: 2.76e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 732 FTQQVQVIEMLQKVTLDIK--SLSAEKYDVSSQVISQLKQK-----LENLQNsqlpesfrvPYDPGLKAGALAIEKCKVM 804
Cdd:cd05173    4 LSKQVEALNKLKTLNSLIKlnAVKLSKAKGKEAMHTCLRQSayreaLSDLQS---------PLNPSIILSELNVEKCKYM 74

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767948061 805 ASKKKPLWLEFkcaDPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDK 875
Cdd:cd05173   75 DSKMKPLWIVY---NNKLFGGDSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVPYGCLATGDR 142
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 786-875 5.33e-26

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: 110.91  E-value: 5.33e-26
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 786 PYDPGLKAGALAIEKCKVMASKKKPLWLEFKCADPTAlsnETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLL 865
Cdd:cd05174   59 PLDPSIILEEVCVDQCTFMDSKMKPLWIMYSSEEAGA---GNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMT 135

                         90
                 ....*....|
gi 767948061 866 PYGCISTGDK 875
Cdd:cd05174  136 PYGCLSTGDK 145
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 734-878 1.86e-23

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: 102.61  E-value: 1.86e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 734 QQVQVIEMLQKVTLDIKSLSAEKydvsSQVISQLKQKLE--NLQNSQLPESFRVPYDPGLKAGALAIEKCKVMASKKKPL 811
Cdd:cd00896    6 RQQEFVDRLRSLMKEVKNEKGSR----DKKIERLRELLSdsELGLLLFFEPLPLPLDPSVKVTGIIPEKSTVFKSALMPL 81

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 767948061 812 WLEFKCADPtalsnETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKiDG 878
Cdd:cd00896   82 KLTFKTLDG-----GEYKVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPN-DG 142
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 731-873 1.52e-22

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: 100.35  E-value: 1.52e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 731 DFTQQVQVIEMLQKVTLDIKSLS-AEKYDVSSQVISQLKQKLENLQnsqlpeSFRVPYDPGLKAGALAIEKCKVMASKKK 809
Cdd:cd05177    3 EFSKETKLISILIDAAEKVKTASdTRRKEVLKREASRLEDFFQDVV------SCCLPLNPALRVKGIDADACSYFTSNAA 76

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767948061 810 PLWLEFKCADPTAlsnETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTG 873
Cdd:cd05177   77 PLKISFINANPLA---KNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYRCLSTG 137
PI3Kc_C2_alpha cd05176
Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 731-873 7.35e-21

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: 95.05  E-value: 7.35e-21
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 731 DFTQQVQVIEMLQKVTLDIKSLSAEKYDVSsqvisqLKQKLENLQNSQLPESFRVPYDPGLKAGALAIEKCKVMASKKKP 810
Cdd:cd05176    3 ELEKQTRLVQLLGRVAEKVRQASGSARQVA------LQDGMERVQSFFQKNKCRLPLSPSLVAKELNIKACSFFSSNAVP 76

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 767948061 811 LWLEFKCADPTAlsnETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTG 873
Cdd:cd05176   77 LKVALVNADPLG---EEINVMFKVGEDLRQDMLALQMIKIMDKIWLQEGLDLRMVIFKCLSTG 136
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
 794-876 4.19e-20

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: 89.70  E-value: 4.19e-20
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 794 GALAIEKCKVMASKKKPLWLEFKCADptalsNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTG 873
Cdd:cd00142    1 NALDVGILKVIHSKQRPKKITLIGAD-----GKTYSFLLKRRDDLRKDERSFQFMRLIQSILEKESVNLVLPPYKVIPLS 75


                 ...
gi 767948061 874 DKI 876
Cdd:cd00142   76 ENS 78
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 352-523 2.40e-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: 86.21  E-value: 2.40e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 352 VSLWDCDRKFRVKIRGIDiPVLPRNTDLTVFVEANIQHGQQVLC-QRRTSPKPFTEEVLWNVWLEFSIKIKDLPKGALLN 430
Cdd:cd08693    1 KSLWDIEEKFSITLHKIS-NLNAAERTMKVGVQAGLFHGGESLCkTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLC 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 431 LQIY--CGKAPALSSKasaespSSESKGKVQLLYY----VNLLLIDHRFLLRRGEYVLHMWQISgkgEDQGSFNADKL-T 503
Cdd:cd08693   80 FAIYevSKKAKGKRSR------KNQTKKKKKKDDNpiawVNTMVFDYKGQLKTGDHTLYMWTYA---EDQSEDLLNPLgT 150

                        170       180
                 ....*....|....*....|
gi 767948061 504 SATNPDKENSMSISILLDNY 523
Cdd:cd08693  151 VESNPNTESATALHISFPEY 170
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 731-873 2.30e-18

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: 87.75  E-value: 2.30e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 731 DFTQQVQVIEMLQKVTLDIKSLSAEkydvSSQVIsqLKQKLENL-QNSQLPESFRVPYDPGLKAGALAIEKCKVMASKKK 809
Cdd:cd00895    3 EFDRQCWLVNVLAKLAQQVREAAPS----ARQGI--LREGLEEVkQFFSINGSCRLPLSPSLLVKGIVPRDCSYFNSNAV 76

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 767948061 810 PLWLEFKCADPTAlsnETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTG 873
Cdd:cd00895   77 PLKLSFQNVDPLG---ENIRVIFKCGDDLRQDMLTLQMIRIMNKIWVQEGLDMRMVIFRCFSTG 137
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 830-876 3.50e-13

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: 70.02  E-value: 3.50e-13
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|.
gi 767948061   830 IIFKHGDDLRQDMLILQILRIMESIWETES----LDLCLLPYGCISTGDKI 876
Cdd:smart00146   1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDKetrrRDLHLRPYKVIPTGPKS 51
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
 799-873 2.38e-12

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: 68.77  E-value: 2.38e-12
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 799 EKCKVMASKKK-PLWLEFKCADPTALSNETIGI------------IFKHGDDLRQDMLILQILRIMESIWETESLDLCLL 865
Cdd:cd05167    8 KSGKPLQSAAKaPFLVTFKVKDCGVDELEHEGTeseatkevwqaaIFKVGDDCRQDMLALQLISLFKNIFEEVGLDLYLF 87


                 ....*...
gi 767948061 866 PYGCISTG 873
Cdd:cd05167   88 PYRVVATG 95
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 828-875 3.01e-12

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: 67.35  E-value: 3.01e-12
                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 767948061  828 IGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLL-PYGCISTGDK 875
Cdd:pfam00454   2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLRRLkPYSVIPLGPK 50
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 381-486 9.09e-10

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: 9.09e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061  381 VFVEANIQHGQQVLCQR-RTSPKPF-TEEVLWNVWLEFSIKIKDLPKGALLNLQIYCGKAPalsskasaespssesKGKV 458
Cdd:pfam00792   5 LYVECQLYHGGKPLCLPvSTRYVPFsNSSIKWNEWITFPIQISDLPRSARLCITIWDVSGP---------------EKSF 69

                          90       100
                  ....*....|....*....|....*...
gi 767948061  459 QLLYYVNLLLIDHRFLLRRGEYVLHMWQ 486
Cdd:pfam00792  70 VPIGWVNTSLFDKKGILRQGKQKLRLWP 97
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
 830-875 3.78e-09

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: 58.81  E-value: 3.78e-09
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*.
gi 767948061 830 IIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDK 875
Cdd:cd00893   30 LIVKTGDDLKQEQLALQLISQFDQIFKEEGLPLWLRPYEILSLGPD 75
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 382-485 2.84e-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: 54.29  E-value: 2.84e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 382 FVEANIQHGQQVLCQRRTSP-----KPFTEEVLWNVWLEFSIKIKDLPKGALLNLQIYCGKAPALSSkasaesPSSESKG 456
Cdd:cd04012   32 YLSCSLYHGGRLLCSPVTTKpvkitKSFFPRVVWDEWIEFPIPVCQLPRESRLVLTLYGTTSSPDGG------SNKQRMG 105

                         90       100
                 ....*....|....*....|....*....
gi 767948061 457 KVQlLYYVNLLLIDHRFLLRRGEYVLHMW 485
Cdd:cd04012  106 PEE-LGWVSLPLFDFRGVLRQGSLLLGLW 133
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
739-877 3.86e-08

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 57.49  E-value: 3.86e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061  739 IEMLQKVtldIKSLSAEKYDVSSQVISQLKQKLENLQ----------NSQLP--ESFRVPYDPGLKAGALAIEK-----C 801
Cdd:COG5032  1699 IRKKFKI---DISLLNLSRKLYISVLRSIRKRLKRLLelrlkkvspkLLLFHafLEIKLPGQYLLDKPFVLIERfepevS 1775

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061  802 KVMASKKKPLWLEFKCADptalsNETIGIIFKHGDDLRQDMLILQILRIMESIW----ETESLDLCLLPYGCISTGDKID 877
Cdd:COG5032  1776 VVKSHLQRPRRLTIRGSD-----GKLYSFIVKGGDDLRQDELALQLIRLMNKILkkdkETRRRDLWIRPYKVIPLSPGSG 1850
C2_PI3K_class_I_alpha cd08398
C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 353-527 4.24e-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: 53.26  E-value: 4.24e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 353 SLWDCDRKFRVKIR-GIDIPVLPRNTdltVFVEANIQHGQQVLCQRRTSPKPFTEEVLWNVWLEFSIKIKDLPKGALLNL 431
Cdd:cd08398    2 SLWKINSNLRIKILcATYVNVNDIDK---IYVRTGIYHGGEPLCDNVNTQRVPCSNPRWNEWLDYDIYIPDLPRSARLCL 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 767948061 432 QIycgkapaLSSKasaespssESKGKVQ---LLYYVNLLLIDHRFLLRRGEYVLHMWQISGKGEDQgsFNADKLTsATNP 508
Cdd:cd08398   79 SI-------CSVK--------GRKGAKEehcPLAWGNINLFDYTDTLVSGKMALNLWPVPHGLEDL--LNPIGVT-GSNP 140

                        170
                 ....*....|....*....
gi 767948061 509 DKEnSMSISILLDNYCHPI 527
Cdd:cd08398  141 NKD-TPCLELEFDRFSCVV 158
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
 828-874 6.95e-08

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: 54.79  E-value: 6.95e-08
                         10        20        30        40
                 ....*....|....*....|....*....|....*....|....*..
gi 767948061 828 IGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGD 874
Cdd:cd05168   31 RSVIVKSGDDLRQELLAMQLIKQFQRIFEEAGLPLWLRPYEILVTSS 77
C2_PI3K_class_III cd08397
C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 375-434 4.19e-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: 47.63  E-value: 4.19e-06
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 767948061 375 RNTDLtvFVEANIQHGQQVLC-QRRTSPKPFTEEVLWNVWLEFSIKIKDLPKGALLNLQIY 434
Cdd:cd08397   28 PNSDL--FVTCQVFDDGKPLTlPVQTSYKPFKNRRNWNEWLTLPIKYSDLPRNSQLAITIW 86
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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