NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|1207171262|ref|XP_021330656|]
View 

phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform isoform X1 [Danio rerio]

Protein Classification

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 739-1105 0e+00

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


:

Pssm-ID: 270627 [Multi-domain]  Cd Length: 367  Bit Score: 725.89  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  739 LQDFRKQVEITEALQKVAREIKQISAEKYDISAQVVFQLRQKLEGLQVLGLPDSFKVPYDPGLRAGALVIEQCKVMASKK 818
Cdd:cd00894      1 LHDFTQQVQVIEMLQKVTLDIKSLSAEKYDVSSQVISQLKQKLENLQNSQLPESFRVPYDPGLRAGALVIEKCKVMASKK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  819 KPLWLQFKRADPTTLSSDTIGIIFKDGDDLRQDMLILQILLIMESIWELESLDLSLLPYGCISTGNKIGMIEIVKDATTI 898
Cdd:cd00894     81 KPLWLEFKCADPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTI 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  899 ANIQQSTVGNTGAFKDEILSQWLREKCVNEDKHQQAVDRFVFSCGGYCVATYVLGIGDRHNDNIMITETGNLFHIDFGHI 978
Cdd:cd00894    161 AKIQQSTVGNTGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHI 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  979 LGNYKSFLGISKERVPFVLTPDFLYLMGTTGKKSSPNFLQFQNVCLKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 1058
Cdd:cd00894    241 LGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSLHFQKFQDVCVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 320

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*..
gi 1207171262 1059 EYIREALTVGRSEDEAKQHFLDQIEICRDKGWTVQFNWFLHLVLGIK 1105
Cdd:cd00894    321 EYIRDALTVGKSEEDAKKHFLDQIEVCRDKGWTVQFNWFLHLVLGIK 367
PIK3CG_ABD pfam19710
PIK3 catalytic subunit gamma adaptor-binding domain; This is the N-terminal domain from ...
 16-208 4.16e-118

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: 362.16  E-value: 4.16e-118
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262   16 MEQ-QASDDEPPVVRREENKRRRRRM-KAFTSASAVSMEHIAVEFVLPTTNKNSKTLDTLQLDVTGNWTVEQVKVQLWHR 93
Cdd:pfam19710    1 SEQmQLSDHEQPVVMREENRRRRRRMkKAFTSASSSSMELISIEFVLPTSNKNTKTPDTLLLEVAGNWTVEQVKAQVWLR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262   94 AVTSKLCPEFYQKYSPDYCILLYQKKGNWYEIYDKQQVFQTLDCIRYWKALRKDVGKIHLVVRQQPAEDSLQYQRFLNHL 173
Cdd:pfam19710   81 AVETNLCPDFYQKFSPDQFILLYQKKGQWYEIYDKHQVFQTLDCIRYWKALQKDVGKIHLVQRPQPSEESLQYQRQLNYL 160

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1207171262  174 IGYDVTDVSNVHDDELEFTRRKLLTPRKIELSDRD 208
Cdd:pfam19710  161 IGYDVTDVSNVHDDELEFTRRKLVTPRMIELSDRD 195
C2_PI3K_class_I_gamma cd08399
C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 366-537 9.27e-97

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: 304.53  E-value: 9.27e-97
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  366 FTISLWDCNRKFRVKILGIDIPVLPRNSELIVFVEASIFHGQQLLAQERTSSKPFTEEVIWNTWLEFNIKIKDLPKGARL 445
Cdd:cd08399      1 FTVSLWDCDRKFRVKILGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFTEEVLWNTWLEFDIKIKDLPKGALL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  446 SLQVSCGKAQTQTSKET------ECKNKSRLLYYVNLLLVDHRSLLRQGEFILHMWKMPEKSEDNSSVNADKLTSATNPD 519
Cdd:cd08399     81 NLQIYCGKAPALSSKKSaespssESKGKHQLLYYVNLLLIDHRFLLRTGEYVLHMWQISGKGEDQGSVNADKLTSATNPD 160

                          170
                   ....*....|....*...
gi 1207171262  520 KNNSMAVAILLDKYCYPV 537
Cdd:cd08399    161 KENSMSISILLDNYCHPV 178
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 559-735 3.97e-91

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: 289.21  E-value: 3.97e-91
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  559 NHLRKQFEQIIATDPLHPLTSEDKELLWHFRQECMRDPKAYPKFLSSVKWGKQEAVAITHYLLERstiwdRSVLDVGLVL 638
Cdd:cd00872      1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRKKPQALPKLLLSVKWNKRDDVAQMYQLLKR-----WPKLKPEQAL 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  639 QLLDCHFSDENVRTIAVRKLETLGDDDVLRYLLQLVQAVKFEPYHDSALARFLLKRALRSKRIGHFLFWFLRSEIAQSMH 718
Cdd:cd00872     76 ELLDCNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSV 155

                          170
                   ....*....|....*..
gi 1207171262  719 yQQRYAVILEAYLRGCG 735
Cdd:cd00872    156 -SQRFGLLLEAYLRGCG 171
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 221-327 7.08e-24

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: 97.36  E-value: 7.08e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  221 TPMPEYLLsKISNNHILMVIHKE--TTSQTIKVSIDDTPVQVLQSFFAKitnKRALLGISEdvSESDFVLRVCGREEYLY 298
Cdd:pfam00794    3 TVSPEPLP-KLINNKLLISVHLEgdQMTKTFTCNPNSTPGSLIAQALTK---KLSVHTQGD--VTDDYVLKVCGRDEYLL 76

                           90       100
                   ....*....|....*....|....*....
gi 1207171262  299 GNNAIKDFHWIRQCLKNGEEIHLVLEHPP 327
Cdd:pfam00794   77 GDHPLGQFEYIRNCLKSGREPHLTLVEQS 105
 
Name Accession Description Interval E-value
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 739-1105 0e+00

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


Pssm-ID: 270627 [Multi-domain]  Cd Length: 367  Bit Score: 725.89  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  739 LQDFRKQVEITEALQKVAREIKQISAEKYDISAQVVFQLRQKLEGLQVLGLPDSFKVPYDPGLRAGALVIEQCKVMASKK 818
Cdd:cd00894      1 LHDFTQQVQVIEMLQKVTLDIKSLSAEKYDVSSQVISQLKQKLENLQNSQLPESFRVPYDPGLRAGALVIEKCKVMASKK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  819 KPLWLQFKRADPTTLSSDTIGIIFKDGDDLRQDMLILQILLIMESIWELESLDLSLLPYGCISTGNKIGMIEIVKDATTI 898
Cdd:cd00894     81 KPLWLEFKCADPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTI 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  899 ANIQQSTVGNTGAFKDEILSQWLREKCVNEDKHQQAVDRFVFSCGGYCVATYVLGIGDRHNDNIMITETGNLFHIDFGHI 978
Cdd:cd00894    161 AKIQQSTVGNTGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHI 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  979 LGNYKSFLGISKERVPFVLTPDFLYLMGTTGKKSSPNFLQFQNVCLKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 1058
Cdd:cd00894    241 LGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSLHFQKFQDVCVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 320

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*..
gi 1207171262 1059 EYIREALTVGRSEDEAKQHFLDQIEICRDKGWTVQFNWFLHLVLGIK 1105
Cdd:cd00894    321 EYIRDALTVGKSEEDAKKHFLDQIEVCRDKGWTVQFNWFLHLVLGIK 367
PIK3CG_ABD pfam19710
PIK3 catalytic subunit gamma adaptor-binding domain; This is the N-terminal domain from ...
 16-208 4.16e-118

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: 362.16  E-value: 4.16e-118
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262   16 MEQ-QASDDEPPVVRREENKRRRRRM-KAFTSASAVSMEHIAVEFVLPTTNKNSKTLDTLQLDVTGNWTVEQVKVQLWHR 93
Cdd:pfam19710    1 SEQmQLSDHEQPVVMREENRRRRRRMkKAFTSASSSSMELISIEFVLPTSNKNTKTPDTLLLEVAGNWTVEQVKAQVWLR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262   94 AVTSKLCPEFYQKYSPDYCILLYQKKGNWYEIYDKQQVFQTLDCIRYWKALRKDVGKIHLVVRQQPAEDSLQYQRFLNHL 173
Cdd:pfam19710   81 AVETNLCPDFYQKFSPDQFILLYQKKGQWYEIYDKHQVFQTLDCIRYWKALQKDVGKIHLVQRPQPSEESLQYQRQLNYL 160

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1207171262  174 IGYDVTDVSNVHDDELEFTRRKLLTPRKIELSDRD 208
Cdd:pfam19710  161 IGYDVTDVSNVHDDELEFTRRKLVTPRMIELSDRD 195
C2_PI3K_class_I_gamma cd08399
C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 366-537 9.27e-97

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: 304.53  E-value: 9.27e-97
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  366 FTISLWDCNRKFRVKILGIDIPVLPRNSELIVFVEASIFHGQQLLAQERTSSKPFTEEVIWNTWLEFNIKIKDLPKGARL 445
Cdd:cd08399      1 FTVSLWDCDRKFRVKILGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFTEEVLWNTWLEFDIKIKDLPKGALL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  446 SLQVSCGKAQTQTSKET------ECKNKSRLLYYVNLLLVDHRSLLRQGEFILHMWKMPEKSEDNSSVNADKLTSATNPD 519
Cdd:cd08399     81 NLQIYCGKAPALSSKKSaespssESKGKHQLLYYVNLLLIDHRFLLRTGEYVLHMWQISGKGEDQGSVNADKLTSATNPD 160

                          170
                   ....*....|....*...
gi 1207171262  520 KNNSMAVAILLDKYCYPV 537
Cdd:cd08399    161 KENSMSISILLDNYCHPV 178
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 559-735 3.97e-91

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: 289.21  E-value: 3.97e-91
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  559 NHLRKQFEQIIATDPLHPLTSEDKELLWHFRQECMRDPKAYPKFLSSVKWGKQEAVAITHYLLERstiwdRSVLDVGLVL 638
Cdd:cd00872      1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRKKPQALPKLLLSVKWNKRDDVAQMYQLLKR-----WPKLKPEQAL 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  639 QLLDCHFSDENVRTIAVRKLETLGDDDVLRYLLQLVQAVKFEPYHDSALARFLLKRALRSKRIGHFLFWFLRSEIAQSMH 718
Cdd:cd00872     76 ELLDCNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSV 155

                          170
                   ....*....|....*..
gi 1207171262  719 yQQRYAVILEAYLRGCG 735
Cdd:cd00872    156 -SQRFGLLLEAYLRGCG 171
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 840-1056 3.31e-69

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: 231.42  E-value: 3.31e-69
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262   840 IIFKDGDDLRQDMLILQILLIMESIWELESLDLSL----LPYGCISTGNKIGMIEIVKDATTIANIQ------------- 902
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDKETRRRdlhlRPYKVIPTGPKSGLIEVVPNSTTLHEILkeyrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262   903 -----------QSTVGNTGAFKDEILSQWLREKcvNED---KHQQAVDRFVFSCGGYCVATYVLGIGDRHNDNIMITETG 968
Cdd:smart00146   81 rsqtatrlkklELFLEATGKFPDPVLYDWFTKK--FPDpseDYFEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTG 158

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262   969 NLFHIDFGHILGNYKSFLGIsKERVPFVLTPDFLYLMGTTGkksspNFLQFQNVCLKAYLALRHHTNLLIILFSMMLMTG 1048
Cdd:smart00146  159 HLFHIDFGFILGNGPKLFGF-PERVPFRLTPEMVDVMGDSG-----YFGLFRSLCERALRALRKNSNLIMSLLELMLYDG 232


                    ....*...
gi 1207171262  1049 MPQLTSKE 1056
Cdd:smart00146  233 LPDWRSGK 240
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 556-743 1.05e-66

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: 222.21  E-value: 1.05e-66
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  556 EMPNHLRKQFEQIIATDPLHPLTSEDKELLWHFRQECMRDPKAYPKFLSSVKWGKQEAVAITHYLLERstiWDRsvLDVG 635
Cdd:pfam00613    4 KPNEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYLMLVPKALTKLLLSVKWSDLSEVAEALSLLLK---WAP--IDPV 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  636 LVLQLLDCHFSDENVRTIAVRKLETLGDDDVLRYLLQLVQAVKFEPYHDSALARFLLKRALRSKRIGHFLFWFLRSEIAQ 715
Cdd:pfam00613   79 DALELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEIHD 158

                          170       180
                   ....*....|....*....|....*...
gi 1207171262  716 SmHYQQRYAVILEAYLRGCGEEMLQDFR 743
Cdd:pfam00613  159 E-EVSPRFGSLLELYLRSCGTSLLGLNK 185
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 561-743 7.76e-66

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: 219.82  E-value: 7.76e-66
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262   561 LRKQFEQIIATDPLHPLTSEDKELLWHFRQEC-MRDPKAYPKFLSSVKWGKQEAVAITHYLLERstiWDRsvLDVGLVLQ 639
Cdd:smart00145    7 EREQLEAILKLDPTYELTEEEKDLIWKFRHYYlTNNPKALPKFLLSVKWSDADEVAQALSLLLS---WAP--LDPEDALE 81

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262   640 LLDCHFSDENVRTIAVRKLETLGDDDVLRYLLQLVQAVKFEPYHDSALARFLLKRALRSKRIGHFLFWFLRSEIaQSMHY 719
Cdd:smart00145   82 LLDPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSEL-HDPHV 160

                           170       180
                    ....*....|....*....|....
gi 1207171262   720 QQRYAVILEAYLRGCGEEMLQDFR 743
Cdd:smart00145  161 SIRFGLLLEAYLRGCGTHLKELLK 184
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 838-1054 9.92e-61

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: 207.57  E-value: 9.92e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  838 IGIIFKDGDDLRQDMLILQILLIMESIWELESL-DLSLLPYGCISTGNKIGMIEIVKDATTIANIQQ----STVGNTGAF 912
Cdd:pfam00454    2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLdLRRLKPYSVIPLGPKCGIIEWVPNSETLAYILDeygeNGVPPTAMV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  913 KD-----------------------EILSQWLREKCVNEDKHQQAVDRFVFSCGGYCVATYVLGIGDRHNDNIMI-TETG 968
Cdd:pfam00454   82 KIlhsalnypklklefesrislppkVGLLQWFVKKSPDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTTG 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  969 NLFHIDFGHILGNYKSFLGIsKERVPFVLTPDFLYLMGTTGKksspnFLQFQNVCLKAYLALRHHTNLLIILFSMMLMTG 1048
Cdd:pfam00454  162 KLFHIDFGLCLPDAGKDLPF-PEKVPFRLTREMVYAMGPSGD-----EGLFRELCETAYEALRRNLNLLTNLLKLMVADG 235


                   ....*.
gi 1207171262 1049 MPQLTS 1054
Cdd:pfam00454  236 LPDWSI 241
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
840-1045 1.30e-34

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 144.54  E-value: 1.30e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  840 IIFKDGDDLRQDMLILQILLIMESIWELESLDLSLL----PYGCISTGNKIGMIEIVKDATTIANI-------------- 901
Cdd:COG5032   1799 FIVKGGDDLRQDELALQLIRLMNKILKKDKETRRRDlwirPYKVIPLSPGSGIIEWVPNSDTLHSIlreyhkrknisidq 1878

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  902 ----QQSTVGNTGAFKDE-----------ILSQWLREKCVNEDKHQQAVDRFVFSCGGYCVATYVLGIGDRHNDNIMITE 966
Cdd:COG5032   1879 ekklAARLDNLKLLLKDEfftkatlksppVLYDWFSESFPNPEDWLTARTNFARSLAVYSVIGYILGLGDRHPGNILIDR 1958

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  967 -TGNLFHIDFGHILGNYKSFLGIsKERVPFVLTPDFLYLMGTTGKKSSpnflqFQNVCLKAYLALRHHTNLLIILFSMML 1045
Cdd:COG5032   1959 sSGHVIHIDFGFILFNAPGRFPF-PEKVPFRLTRNIVEAMGVSGVEGS-----FRELCETAFRALRKNADSLMNVLELFV 2032
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 365-462 1.71e-25

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 101.65  E-value: 1.71e-25
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262   365 VFTISLWDCNRKFRVKILGIDIPVLPRNSELI-VFVEASIFHGQQLL-AQERTSSKPFTEEVIWNTWLEFNIKIKDLPKG 442
Cdd:smart00142    1 VKIESLWDCDRNLVITIALIHGIPLNWSRDYSdLYVEIQLYHGGKLLcLPVSTSYKPFFPSVKWNEWLTFPIQISDLPRE 80

                            90       100
                    ....*....|....*....|
gi 1207171262   443 ARLSLQVSCGKAQTQTSKET 462
Cdd:smart00142   81 ARLCITIYAVKNPSKGSEFG 100
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 221-327 7.08e-24

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: 97.36  E-value: 7.08e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  221 TPMPEYLLsKISNNHILMVIHKE--TTSQTIKVSIDDTPVQVLQSFFAKitnKRALLGISEdvSESDFVLRVCGREEYLY 298
Cdd:pfam00794    3 TVSPEPLP-KLINNKLLISVHLEgdQMTKTFTCNPNSTPGSLIAQALTK---KLSVHTQGD--VTDDYVLKVCGRDEYLL 76

                           90       100
                   ....*....|....*....|....*....
gi 1207171262  299 GNNAIKDFHWIRQCLKNGEEIHLVLEHPP 327
Cdd:pfam00794   77 GDHPLGQFEYIRNCLKSGREPHLTLVEQS 105
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 219-323 4.09e-22

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: 92.39  E-value: 4.09e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262   219 TTTPMPEYLLSKISNNHILMVIHKE--TTSQTIKVSIDDTPVQVLQSFFAKitnKRALLGiSEDVSESDFVLRVCGREEY 296
Cdd:smart00144    1 TSPSVPEPLPLKTIANKILIVVHLEkdQQTKTLKVNPNCTPDSVLAQAFTK---MLSLHD-QVDPTSEDYILKVCGRDEY 76

                            90       100
                    ....*....|....*....|....*..
gi 1207171262   297 LYGNNAIKDFHWIRQCLKNGEEIHLVL 323
Cdd:smart00144   77 LLGDHPLGSFEYIRNCLKNGTEPHLVL 103
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 397-495 1.05e-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: 60.46  E-value: 1.05e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  397 VFVEASIFHGQQLLAQ-ERTSSKPFTEEVI-WNTWLEFNIKIKDLPKGARLSLQVSCGKAQTQTSKETECKNKSrllyyv 474
Cdd:pfam00792    5 LYVECQLYHGGKPLCLpVSTRYVPFSNSSIkWNEWITFPIQISDLPRSARLCITIWDVSGPEKSFVPIGWVNTS------ 78

                           90       100
                   ....*....|....*....|.
gi 1207171262  475 nllLVDHRSLLRQGEFILHMW 495
Cdd:pfam00792   79 ---LFDKKGILRQGKQKLRLW 96
PTZ00303 PTZ00303
phosphatidylinositol kinase; Provisional
 933-986 6.12e-03

phosphatidylinositol kinase; Provisional


Pssm-ID: 140324 [Multi-domain]  Cd Length: 1374  Bit Score: 40.84  E-value: 6.12e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1207171262  933 QAVDRFVFSCGGYCVATYVLGIGDRHNDNIMITETGNLFHIDFGHILGNyKSFL 986
Cdd:PTZ00303  1128 RSCINFLASAKLFLLLNYIFSIGDRHKGNVLIGTNGALLHIDFRFIFSE-KTFV 1180
 
Name Accession Description Interval E-value
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 739-1105 0e+00

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


Pssm-ID: 270627 [Multi-domain]  Cd Length: 367  Bit Score: 725.89  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  739 LQDFRKQVEITEALQKVAREIKQISAEKYDISAQVVFQLRQKLEGLQVLGLPDSFKVPYDPGLRAGALVIEQCKVMASKK 818
Cdd:cd00894      1 LHDFTQQVQVIEMLQKVTLDIKSLSAEKYDVSSQVISQLKQKLENLQNSQLPESFRVPYDPGLRAGALVIEKCKVMASKK 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  819 KPLWLQFKRADPTTLSSDTIGIIFKDGDDLRQDMLILQILLIMESIWELESLDLSLLPYGCISTGNKIGMIEIVKDATTI 898
Cdd:cd00894     81 KPLWLEFKCADPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTI 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  899 ANIQQSTVGNTGAFKDEILSQWLREKCVNEDKHQQAVDRFVFSCGGYCVATYVLGIGDRHNDNIMITETGNLFHIDFGHI 978
Cdd:cd00894    161 AKIQQSTVGNTGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHI 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  979 LGNYKSFLGISKERVPFVLTPDFLYLMGTTGKKSSPNFLQFQNVCLKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 1058
Cdd:cd00894    241 LGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSLHFQKFQDVCVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 320

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*..
gi 1207171262 1059 EYIREALTVGRSEDEAKQHFLDQIEICRDKGWTVQFNWFLHLVLGIK 1105
Cdd:cd00894    321 EYIRDALTVGKSEEDAKKHFLDQIEVCRDKGWTVQFNWFLHLVLGIK 367
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 739-1101 1.86e-175

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: 518.34  E-value: 1.86e-175
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  739 LQDFRKQVEITEALQKVAREIKqisaEKYDISAQVVFQLRQKLEGLQVLGLPDSFKVPYDPGLRAGALVIEQCKVMASKK 818
Cdd:cd05165      1 LKSLSRQVEALNKLKKLSDILK----EKKKSKEKVKKLLKECLKQKFYDEALQNFQSPLNPSHKLGELIIEKCKVMDSKK 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  819 KPLWLQFKRADPTTLSSDTIGIIFKDGDDLRQDMLILQILLIMESIWELESLDLSLLPYGCISTGNKIGMIEIVKDATTI 898
Cdd:cd05165     77 RPLWLVFENADPLALSGEDIKIIFKNGDDLRQDMLTLQIIRIMDNIWKEEGLDLRMLPYGCLSTGDNVGLIEVVRNAKTI 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  899 ANIQQSTVGN-TGAFKDEILSQWLREKCVNEDKHQQAVDRFVFSCGGYCVATYVLGIGDRHNDNIMITETGNLFHIDFGH 977
Cdd:cd05165    157 ANIQKKKGKVaTLAFNKDSLHKWLKEKNKTGEKYDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVKENGQLFHIDFGH 236

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  978 ILGNYKSFLGISKERVPFVLTPDFLYLMGTTGKKS-SPNFLQFQNVCLKAYLALRHHTNLLIILFSMMLMTGMPQLTSKE 1056
Cdd:cd05165    237 FLGNFKKKFGIKRERVPFVLTHDFVYVIARGQDNTkSEEFQEFQELCEKAYLILRRHGNLFISLFSMMLSTGIPELTSVK 316

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*
gi 1207171262 1057 DIEYIREALTVGRSEDEAKQHFLDQIEICRDKGWTVQFNWFLHLV 1101
Cdd:cd05165    317 DIEYLRKTLALDKTEEEALKYFRKKFNEALKGSWTTKVNWFFHNV 361
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 740-1087 1.25e-166

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: 494.40  E-value: 1.25e-166
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  740 QDFRKQVEITEALQKVAREIKQISAEKydisaqvvfqlRQKL--EGLQVLGLPDSFKVPYDPGLRAGALVIEQCKVMASK 817
Cdd:cd00891      2 EELLKQVKVLDELKEIAKKIKEEPSEE-----------RKEVleKLLQKLELPKKFTLPLDPRMEVKGLIVEKCKVMDSK 70

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  818 KKPLWLQFKRADPTTlssDTIGIIFKDGDDLRQDMLILQILLIMESIWELESLDLSLLPYGCISTGNKIGMIEIVKDATT 897
Cdd:cd00891     71 KLPLWLVFKNADPGG---DPIKVIFKAGDDLRQDQLTLQLLRIMDKLWKKEGLDLRMTPYKCIATGDEVGMIEVVPNSET 147

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  898 IANIQQSTVGNTGAFKDEILSQWLREKCVNEDKHQQAVDRFVFSCGGYCVATYVLGIGDRHNDNIMITETGNLFHIDFGH 977
Cdd:cd00891    148 TAAIQKKYGGFGAAFKDTPISNWLKKHNPTEEEYEEAVENFIRSCAGYCVATYVLGIGDRHNDNIMVTKSGHLFHIDFGH 227

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  978 ILGNYKSFLGISKERVPFVLTPDFLYLMGTtgkKSSPNFLQFQNVCLKAYLALRHHTNLLIILFSMMLMTGMPQLTSKED 1057
Cdd:cd00891    228 FLGNFKKKFGIKRERAPFVFTPEMAYVMGG---EDSENFQKFEDLCCKAYNILRKHGNLLINLFSLMLSAGIPELQSIED 304

                          330       340       350
                   ....*....|....*....|....*....|
gi 1207171262 1058 IEYIREALTVGRSEDEAKQHFLDQIEICRD 1087
Cdd:cd00891    305 IEYLRDALQLDLSDEEAAEHFRKLIHESLN 334
PIK3CG_ABD pfam19710
PIK3 catalytic subunit gamma adaptor-binding domain; This is the N-terminal domain from ...
 16-208 4.16e-118

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: 362.16  E-value: 4.16e-118
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262   16 MEQ-QASDDEPPVVRREENKRRRRRM-KAFTSASAVSMEHIAVEFVLPTTNKNSKTLDTLQLDVTGNWTVEQVKVQLWHR 93
Cdd:pfam19710    1 SEQmQLSDHEQPVVMREENRRRRRRMkKAFTSASSSSMELISIEFVLPTSNKNTKTPDTLLLEVAGNWTVEQVKAQVWLR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262   94 AVTSKLCPEFYQKYSPDYCILLYQKKGNWYEIYDKQQVFQTLDCIRYWKALRKDVGKIHLVVRQQPAEDSLQYQRFLNHL 173
Cdd:pfam19710   81 AVETNLCPDFYQKFSPDQFILLYQKKGQWYEIYDKHQVFQTLDCIRYWKALQKDVGKIHLVQRPQPSEESLQYQRQLNYL 160

                          170       180       190
                   ....*....|....*....|....*....|....*
gi 1207171262  174 IGYDVTDVSNVHDDELEFTRRKLLTPRKIELSDRD 208
Cdd:pfam19710  161 IGYDVTDVSNVHDDELEFTRRKLVTPRMIELSDRD 195
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 740-1099 3.48e-112

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: 352.75  E-value: 3.48e-112
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  740 QDFRKQVEITEALQKVAREIKQISaekyDISAQVVfqLRQKLEGLQVLGLPDSFKVPYDPGLRAGALVIEQCKVMASKKK 819
Cdd:cd05166      2 EEFLKQHVLVQALTSIAEKVKSAK----DSARENA--LRRELEQLASFLLENSFRLPLDPALEVTGVDVRSCSYFNSNAL 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  820 PLWLQFKRADPttlSSDTIGIIFKDGDDLRQDMLILQILLIMESIWELESLDLSLLPYGCISTGNKIGMIEIVKDATTIA 899
Cdd:cd05166     76 PLKLVFRNADP---RAEPISVIFKVGDDLRQDMLTLQLIRIMDKIWLQEGLDLKMITFRCVPTGNKRGMVELVPEAETLR 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  900 NIQQStVGNTGAFKDEILSQWLREKCVNEDKHQQAVDRFVFSCGGYCVATYVLGIGDRHNDNIMITETGNLFHIDFGHIL 979
Cdd:cd05166    153 EIQTE-HGLTGSFKDRPLADWLQKHNPSELEYEKAVENFIRSCAGYCVATYVLGICDRHNDNIMLKTSGHLFHIDFGKFL 231

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  980 GNYKSFLGISKERVPFVLTPDFLYLMgTTGKKSSPNFLQFQNVCLKAYLALRHHTNLLIILFSMMLMTGMPQLTSkEDIE 1059
Cdd:cd05166    232 GDAQMFGNFKRDRVPFVLTSDMAYVI-NGGDKPSSRFQLFVDLCCQAFNIIRKNSNLLLNLLSLMLSSGIPGVTQ-DDLR 309

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|
gi 1207171262 1060 YIREALTVGRSEDEAKQHFLDQIEICRdKGWTVQFNWFLH 1099
Cdd:cd05166    310 YVQDALLPELTDAEATAHFTRMIEESL-SSKFTQLNFFIH 348
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 796-1101 2.65e-105

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: 335.01  E-value: 2.65e-105
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  796 PYDPGLRAGALVIEQCKVMASKKKPLWLQFkraDPTTLSSDTIGIIFKDGDDLRQDMLILQILLIMESIWELESLDLSLL 875
Cdd:cd05173     56 PLNPSIILSELNVEKCKYMDSKMKPLWIVY---NNKLFGGDSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIV 132

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  876 PYGCISTGNKIGMIEIVKDATTIANIQ--QSTVGNTGAFKDEILSQWLREkCVNEDKHQQAVDRFVFSCGGYCVATYVLG 953
Cdd:cd05173    133 PYGCLATGDRSGLIEVVSSAETIADIQlnSSNVAAAAAFNKDALLNWLKE-YNSGDDLERAIEEFTLSCAGYCVATYVLG 211

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  954 IGDRHNDNIMITETGNLFHIDFGHILGNYKSFLGISKERVPFVLTPDFLYLM--GTTGkkSSPNFLQFQNVCLKAYLALR 1031
Cdd:cd05173    212 IGDRHSDNIMVRKNGQLFHIDFGHILGNFKSKFGIKRERVPFILTYDFIHVIqqGKTG--NTEKFGRFRQYCEDAYLILR 289

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262 1032 HHTNLLIILFSMMLMTGMPQLTSKEDIEYIREALTVGRSEDEAKQHFLDQIEICRDKGWTVQFNWFLHLV 1101
Cdd:cd05173    290 KNGNLFITLFALMLTAGLPELTSVKDIQYLKDSLALGKSEEEALKQFRQKFDEALRESWTTKVNWMAHTV 359
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 796-1101 2.58e-104

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: 332.40  E-value: 2.58e-104
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  796 PYDPGLRAGALVIEQCKVMASKKKPLWLQFKRADPttlSSDTIGIIFKDGDDLRQDMLILQILLIMESIWELESLDLSLL 875
Cdd:cd05174     59 PLDPSIILEEVCVDQCTFMDSKMKPLWIMYSSEEA---GAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMT 135

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  876 PYGCISTGNKIGMIEIVKDATTIANIQ--QSTVGNTGAFKDEILSQWLREKCVNeDKHQQAVDRFVFSCGGYCVATYVLG 953
Cdd:cd05174    136 PYGCLSTGDKTGLIEVVLHSDTIANIQlnKSNMAATAAFNKDALLNWLKSKNPG-DALDQAIEEFTLSCAGYCVATYVLG 214

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  954 IGDRHNDNIMITETGNLFHIDFGHILGNYKSFLGISKERVPFVLTPDFLYLMGTTGKKSSPNFLQFQNVCLKAYLALRHH 1033
Cdd:cd05174    215 IGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRH 294

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207171262 1034 TNLLIILFSMMLMTGMPQLTSKEDIEYIREALTVGRSEDEAKQHFLDQIEICRDKGWTVQFNWFLHLV 1101
Cdd:cd05174    295 GLLFLHLFALMKAAGLPELSCSKDIQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNV 362
C2_PI3K_class_I_gamma cd08399
C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 366-537 9.27e-97

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: 304.53  E-value: 9.27e-97
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  366 FTISLWDCNRKFRVKILGIDIPVLPRNSELIVFVEASIFHGQQLLAQERTSSKPFTEEVIWNTWLEFNIKIKDLPKGARL 445
Cdd:cd08399      1 FTVSLWDCDRKFRVKILGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFTEEVLWNTWLEFDIKIKDLPKGALL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  446 SLQVSCGKAQTQTSKET------ECKNKSRLLYYVNLLLVDHRSLLRQGEFILHMWKMPEKSEDNSSVNADKLTSATNPD 519
Cdd:cd08399     81 NLQIYCGKAPALSSKKSaespssESKGKHQLLYYVNLLLIDHRFLLRTGEYVLHMWQISGKGEDQGSVNADKLTSATNPD 160

                          170
                   ....*....|....*...
gi 1207171262  520 KNNSMAVAILLDKYCYPV 537
Cdd:cd08399    161 KENSMSISILLDNYCHPV 178
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 559-735 3.97e-91

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: 289.21  E-value: 3.97e-91
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  559 NHLRKQFEQIIATDPLHPLTSEDKELLWHFRQECMRDPKAYPKFLSSVKWGKQEAVAITHYLLERstiwdRSVLDVGLVL 638
Cdd:cd00872      1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRKKPQALPKLLLSVKWNKRDDVAQMYQLLKR-----WPKLKPEQAL 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  639 QLLDCHFSDENVRTIAVRKLETLGDDDVLRYLLQLVQAVKFEPYHDSALARFLLKRALRSKRIGHFLFWFLRSEIAQSMH 718
Cdd:cd00872     76 ELLDCNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSV 155

                          170
                   ....*....|....*..
gi 1207171262  719 yQQRYAVILEAYLRGCG 735
Cdd:cd00872    156 -SQRFGLLLEAYLRGCG 171
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 739-1101 1.10e-89

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: 293.12  E-value: 1.10e-89
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  739 LQDFRKQVEITEALQKVAREIKQisaEKYDISAQVVFQ-LRQKLEGLQVLGLPDSFKVPYDPGLRAGALVIEQCKVMASK 817
Cdd:cd05175      5 LKHLSRQVEAMEKLINLTDILKQ---EKKDETQKVQMKfLVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSA 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  818 KKPLWLQFKRAD-PTTLSSDTIGIIFKDGDDLRQDMLILQILLIMESIWELESLDLSLLPYGCISTGNKIGMIEIVKDAT 896
Cdd:cd05175     82 KRPLWLNWENPDiMSELLFQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSH 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  897 TIANIQQSTvGNTGA--FKDEILSQWLREKCVNEdKHQQAVDRFVFSCGGYCVATYVLGIGDRHNDNIMITETGNLFHID 974
Cdd:cd05175    162 TIMQIQCKG-GLKGAlqFNSHTLHQWLKDKNKGE-IYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHID 239

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  975 FGHILGNYKSFLGISKERVPFVLTPDFLYLMGTTGKKSSPN--FLQFQNVCLKAYLALRHHTNLLIILFSMMLMTGMPQL 1052
Cdd:cd05175    240 FGHFLDHKKKKFGYKRERVPFVLTQDFLIVISKGAQECTKTreFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPEL 319

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*....
gi 1207171262 1053 TSKEDIEYIREALTVGRSEDEAKQHFLDQIEICRDKGWTVQFNWFLHLV 1101
Cdd:cd05175    320 QSFDDIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTI 368
PI3Kc_C2_alpha cd05176
Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 740-1099 6.42e-83

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: 273.78  E-value: 6.42e-83
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  740 QDFRKQVEITEALQKVAREIKQISAEkydiSAQVVFQlrQKLEGLQVLGLPDSFKVPYDPGLRAGALVIEQCKVMASKKK 819
Cdd:cd05176      2 EELEKQTRLVQLLGRVAEKVRQASGS----ARQVALQ--DGMERVQSFFQKNKCRLPLSPSLVAKELNIKACSFFSSNAV 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  820 PLWLQFKRADPTtlsSDTIGIIFKDGDDLRQDMLILQILLIMESIWELESLDLSLLPYGCISTGNKIGMIEIVKDATTIA 899
Cdd:cd05176     76 PLKVALVNADPL---GEEINVMFKVGEDLRQDMLALQMIKIMDKIWLQEGLDLRMVIFKCLSTGKDRGMVELVPSSDTLR 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  900 NIQQStVGNTGAFKDEILSQWLREKCVNEDKHQQAVDRFVFSCGGYCVATYVLGIGDRHNDNIMITETGNLFHIDFGHIL 979
Cdd:cd05176    153 KIQVE-YGVTGSFKDKPLAEWLRKYNPSEEEYEKASENFIYSCAGCCVATYVLGICDRHNDNIMLRSTGHMFHIDFGKFL 231

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  980 GNYKSFLGISKERVPFVLTPDFLYLMgTTGKKSSPNFLQFQNVCLKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDIE 1059
Cdd:cd05176    232 GHAQMFGSFKRDRAPFVLTSDMAYVI-NGGEKPTIRFQLFVDLCCQAYNLIRKHTNLFLNLLSLMLSSGLPELTGIQDLK 310

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|
gi 1207171262 1060 YIREALTVGRSEDEAKQHFLDQIEICRDKGWTvQFNWFLH 1099
Cdd:cd05176    311 YVFDALQPQTTDAEATIFFTRLIESSLGSVAT-KFNFFIH 349
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 740-1099 2.53e-77

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: 258.39  E-value: 2.53e-77
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  740 QDFRKQVEITEALQKVAREIKQISAEkydiSAQVVfqLRQKLEGL-QVLGLPDSFKVPYDPGLRAGALVIEQCKVMASKK 818
Cdd:cd00895      2 EEFDRQCWLVNVLAKLAQQVREAAPS----ARQGI--LREGLEEVkQFFSINGSCRLPLSPSLLVKGIVPRDCSYFNSNA 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  819 KPLWLQFKRADPTtlsSDTIGIIFKDGDDLRQDMLILQILLIMESIWELESLDLSLLPYGCISTGNKIGMIEIVKDATTI 898
Cdd:cd00895     76 VPLKLSFQNVDPL---GENIRVIFKCGDDLRQDMLTLQMIRIMNKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETL 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  899 ANIQQSTvGNTGAFKDEILSQWLREKCVNEDKHQQAVDRFVFSCGGYCVATYVLGIGDRHNDNIMITETGNLFHIDFGHI 978
Cdd:cd00895    153 RKIQVEH-GVTGSFKDRPLADWLQKHNPTEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRF 231

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  979 LGNYKSFLGISKERVPFVLTPDFLYLMgTTGKKSSPNFLQFQNVCLKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 1058
Cdd:cd00895    232 LGHAQMFGNIKRDRAPFVFTSDMAYVI-NGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDL 310

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|.
gi 1207171262 1059 EYIREALTVGRSEDEAKQHFLDQIEICRDKGWTvQFNWFLH 1099
Cdd:cd00895    311 KYVYDALRPQDTEADATTYFTRLIESSLGSVAT-KLNFFIH 350
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 740-1083 1.14e-74

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: 251.35  E-value: 1.14e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  740 QDFRKQVEITEALQKVAREIKQIS-AEKYDISAQVVFQLRQKLEGLQVLGLPdsfkvpYDPGLRAGALVIEQCKVMASKK 818
Cdd:cd05177      2 KEFSKETKLISILIDAAEKVKTASdTRRKEVLKREASRLEDFFQDVVSCCLP------LNPALRVKGIDADACSYFTSNA 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  819 KPLWLQFKRADPTtlsSDTIGIIFKDGDDLRQDMLILQILLIMESIWELESLDLSLLPYGCISTGNKIGMIEIVKDATTI 898
Cdd:cd05177     76 APLKISFINANPL---AKNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYRCLSTGKTQGLVQMVPDAVTL 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  899 ANIQQSTvGNTGAFKDEILSQWLREKCVNEDKHQQAVDRFVFSCGGYCVATYVLGIGDRHNDNIMITETGNLFHIDFGHI 978
Cdd:cd05177    153 AKIHRES-GLIGPLKENTIEKWFHMHNKLKEDYDKAVRNFFHSCAGWCVVTFILGVCDRHNDNIMLTHSGHMFHIDFGKF 231

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  979 LGNYKSFLGISKERVPFVLTPDFLYLMgTTGKKSSPNFLQFQNVCLKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 1058
Cdd:cd05177    232 LGHAQTFGSIKRDRAPFIFTSEMEYFI-TEGGKKPQRFQRFVELCCRAYNIVRKHSQLLLNLLEMMLHAGLPELKDIQDL 310

                          330       340
                   ....*....|....*....|....*
gi 1207171262 1059 EYIREALTVGRSEDEAKQHFLDQIE 1083
Cdd:cd05177    311 KYVYNNLRPQDTDLEATSYFTKKIK 335
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 840-1056 3.31e-69

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: 231.42  E-value: 3.31e-69
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262   840 IIFKDGDDLRQDMLILQILLIMESIWELESLDLSL----LPYGCISTGNKIGMIEIVKDATTIANIQ------------- 902
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDKETRRRdlhlRPYKVIPTGPKSGLIEVVPNSTTLHEILkeyrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262   903 -----------QSTVGNTGAFKDEILSQWLREKcvNED---KHQQAVDRFVFSCGGYCVATYVLGIGDRHNDNIMITETG 968
Cdd:smart00146   81 rsqtatrlkklELFLEATGKFPDPVLYDWFTKK--FPDpseDYFEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTG 158

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262   969 NLFHIDFGHILGNYKSFLGIsKERVPFVLTPDFLYLMGTTGkksspNFLQFQNVCLKAYLALRHHTNLLIILFSMMLMTG 1048
Cdd:smart00146  159 HLFHIDFGFILGNGPKLFGF-PERVPFRLTPEMVDVMGDSG-----YFGLFRSLCERALRALRKNSNLIMSLLELMLYDG 232


                    ....*...
gi 1207171262  1049 MPQLTSKE 1056
Cdd:smart00146  233 LPDWRSGK 240
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 556-743 1.05e-66

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: 222.21  E-value: 1.05e-66
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  556 EMPNHLRKQFEQIIATDPLHPLTSEDKELLWHFRQECMRDPKAYPKFLSSVKWGKQEAVAITHYLLERstiWDRsvLDVG 635
Cdd:pfam00613    4 KPNEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYLMLVPKALTKLLLSVKWSDLSEVAEALSLLLK---WAP--IDPV 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  636 LVLQLLDCHFSDENVRTIAVRKLETLGDDDVLRYLLQLVQAVKFEPYHDSALARFLLKRALRSKRIGHFLFWFLRSEIAQ 715
Cdd:pfam00613   79 DALELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEIHD 158

                          170       180
                   ....*....|....*....|....*...
gi 1207171262  716 SmHYQQRYAVILEAYLRGCGEEMLQDFR 743
Cdd:pfam00613  159 E-EVSPRFGSLLELYLRSCGTSLLGLNK 185
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 561-743 7.76e-66

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: 219.82  E-value: 7.76e-66
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262   561 LRKQFEQIIATDPLHPLTSEDKELLWHFRQEC-MRDPKAYPKFLSSVKWGKQEAVAITHYLLERstiWDRsvLDVGLVLQ 639
Cdd:smart00145    7 EREQLEAILKLDPTYELTEEEKDLIWKFRHYYlTNNPKALPKFLLSVKWSDADEVAQALSLLLS---WAP--LDPEDALE 81

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262   640 LLDCHFSDENVRTIAVRKLETLGDDDVLRYLLQLVQAVKFEPYHDSALARFLLKRALRSKRIGHFLFWFLRSEIaQSMHY 719
Cdd:smart00145   82 LLDPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSEL-HDPHV 160

                           170       180
                    ....*....|....*....|....
gi 1207171262   720 QQRYAVILEAYLRGCGEEMLQDFR 743
Cdd:smart00145  161 SIRFGLLLEAYLRGCGTHLKELLK 184
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 743-1083 1.01e-65

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: 225.87  E-value: 1.01e-65
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  743 RKQVEITEALQKVAREIKQISAEKydisAQVVFQLRQKLE--GLQVLGLPDSFKVPYDPGLRAGALVIEQCKVMASKKKP 820
Cdd:cd00896      5 KRQQEFVDRLRSLMKEVKNEKGSR----DKKIERLRELLSdsELGLLLFFEPLPLPLDPSVKVTGIIPEKSTVFKSALMP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  821 LWLQFKradptTLSSDTIGIIFKDGDDLRQDMLILQILLIMESIWELESLDLSLLPYGCISTGNKIGMIEIVKDATTIAN 900
Cdd:cd00896     81 LKLTFK-----TLDGGEYKVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVPNSKALAD 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  901 IQQstvgntgafKDEILSQWLREKcvNEDKHQ------QAVDRFVFSCGGYCVATYVLGIGDRHNDNIMITETGNLFHID 974
Cdd:cd00896    156 ILK---------KYGSILNFLRKH--NPDESGpygikpEVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHID 224

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  975 FGHILGN-YKSFLgiskerVPFVLTPDFLYLMGttGKKsSPNFLQFQNVCLKAYLALRHHTNLLIILFSMMLMTGMP--Q 1051
Cdd:cd00896    225 FGYILGRdPKPFP------PPMKLCKEMVEAMG--GAN-SEGYKEFKKYCCTAYNILRKHANLILNLFSLMVDANIPdiA 295

                          330       340       350
                   ....*....|....*....|....*....|..
gi 1207171262 1052 LTSKEDIEYIREALTVGRSEDEAKQHFLDQIE 1083
Cdd:cd00896    296 LEPDKAVLKVQEKFRLDLSDEEAEQYFQNLID 327
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
 804-1047 6.58e-65

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: 218.74  E-value: 6.58e-65
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  804 GALVIEQCKVMASKKKPLWLQFKRADpttlsSDTIGIIFKDGDDLRQDMLILQILLIMESIWELESLDLSLLPYGCISTG 883
Cdd:cd00142      1 NALDVGILKVIHSKQRPKKITLIGAD-----GKTYSFLLKRRDDLRKDERSFQFMRLIQSILEKESVNLVLPPYKVIPLS 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  884 NKIGMIEIVKDATTIaniqqstvgntgafkdEILSQWLREKCVNEDKHQQAVDRFVFSCGGYCVATYVLGIGDRHNDNIM 963
Cdd:cd00142     76 ENSGLIEIVKDAQTI----------------EDLLKSLWRKSPSSQSWLNRRENFSCSLAGYSVLGYIFGIGDRHPSNIM 139

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  964 ITETGNLFHIDFGHILGNYKSFLGisKERVPFVLTPDFLYLMGTTGKksspnFLQFQNVCLKAYLALRHHTNLLIILFSM 1043
Cdd:cd00142    140 IEPSGNIFHIDFGFIFSGRKLAEG--VETVPFRLTPMLENAMGTAGV-----NGPFQISMVKIMEILREHADLIVPILEH 212


                   ....
gi 1207171262 1044 MLMT 1047
Cdd:cd00142    213 SLRD 216
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 838-1054 9.92e-61

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: 207.57  E-value: 9.92e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  838 IGIIFKDGDDLRQDMLILQILLIMESIWELESL-DLSLLPYGCISTGNKIGMIEIVKDATTIANIQQ----STVGNTGAF 912
Cdd:pfam00454    2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLdLRRLKPYSVIPLGPKCGIIEWVPNSETLAYILDeygeNGVPPTAMV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  913 KD-----------------------EILSQWLREKCVNEDKHQQAVDRFVFSCGGYCVATYVLGIGDRHNDNIMI-TETG 968
Cdd:pfam00454   82 KIlhsalnypklklefesrislppkVGLLQWFVKKSPDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTTG 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  969 NLFHIDFGHILGNYKSFLGIsKERVPFVLTPDFLYLMGTTGKksspnFLQFQNVCLKAYLALRHHTNLLIILFSMMLMTG 1048
Cdd:pfam00454  162 KLFHIDFGLCLPDAGKDLPF-PEKVPFRLTREMVYAMGPSGD-----EGLFRELCETAYEALRRNLNLLTNLLKLMVADG 235


                   ....*.
gi 1207171262 1049 MPQLTS 1054
Cdd:pfam00454  236 LPDWSI 241
PI3Ka cd00864
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 559-713 7.36e-59

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


Pssm-ID: 238440  Cd Length: 152  Bit Score: 198.98  E-value: 7.36e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  559 NHLRKQFEQIIATDPLHPLTSEDKELLWHFRQECMRDPKAYPKFLSSVKWGKQEAVAITHYLLERstiWDRsvLDVGLVL 638
Cdd:cd00864      1 AWERKPLLAILLYPPFSTLTEEEKELLWKFRYYLLNVPKALPKLLKSVNWNDDEEVSELYQLLKW---WAP--LSPEDAL 75

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1207171262  639 QLLDCHFSDENVRTIAVRKLETLGDDDVLRYLLQLVQAVKFEPYHDSALARFLLKRALRSKRIGHFLFWFLRSEI 713
Cdd:cd00864     76 ELLSPKYPDPVVRQYAVRVLESASDDELLLYLPQLVQALKYEPYLDSYLARFLLERALKSQRLGHQLYWNLKSEI 150
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
 841-1105 6.38e-52

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


Pssm-ID: 270711 [Multi-domain]  Cd Length: 307  Bit Score: 185.10  E-value: 6.38e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  841 IFKDGDDLRQDMLILQILLIMESIWELESLDLSLLPYGCISTGNKIGMIEIVKDATTIANIQQSTVGNtgafkdeiLSQW 920
Cdd:cd05167     53 IFKVGDDCRQDMLALQLISLFKNIFEEVGLDLYLFPYRVVATGPGCGVIEVIPNSKSRDQIGRETDNG--------LYEY 124

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  921 LREKCVNEDKH--QQAVDRFVFSCGGYCVATYVLGIGDRHNDNIMITETGNLFHIDFGHIL-----GNyksfLGIskERV 993
Cdd:cd05167    125 FLSKYGDESTPafQKARRNFIKSMAGYSLVSYLLQIKDRHNGNIMIDDDGHIIHIDFGFIFeispgGN----LGF--ESA 198

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  994 PFVLTPDFLYLMGttGKKSSPNFLQFQNVCLKAYLALRHHTNLLIILFSMMLMTGMPQLTsKEDIEYIREALTVGRSEDE 1073
Cdd:cd05167    199 PFKLTKEMVDLMG--GSMESEPFKWFVELCVRGYLAVRPYAEAIVSLVELMLDSGLPCFR-GQTIKNLRERFALEMSERE 275

                          250       260       270
                   ....*....|....*....|....*....|..
gi 1207171262 1074 AKQHFLDQIEICRDKGWTVQFNWFLHLVLGIK 1105
Cdd:cd05167    276 AANFMIKLIADSYLKIRTKGYDMFQYYQNGIP 307
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
 840-1104 4.12e-48

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: 173.22  E-value: 4.12e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  840 IIFKDGDDLRQDMLILQILLIMESIWELESLDLSLLPYGCISTGNKIGMIEIVKDATTIANIQQSTvGNTGAFKDeiLSQ 919
Cdd:cd00893     30 LIVKTGDDLKQEQLALQLISQFDQIFKEEGLPLWLRPYEILSLGPDSGIIEMIKNAVSIDSLKKKL-DSFNKFVS--LSD 106

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  920 WLREKcVNEDKHQQAVDRFVFSCGGYCVATYVLGIGDRHNDNIMITETGNLFHIDFGHILGNYKSFLGIskERVPFVLTP 999
Cdd:cd00893    107 FFDDN-FGDEAIQKARDNFLQSLVAYSLVCYFLQIKDRHNGNILLDKEGHIIHIDFGFFLSSHPGFYGF--EGAPFKLSS 183

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262 1000 DFLYLMGttGKKSSPnFLQFQNVCLKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDIEYIREALTVGRSEDEAKQHFL 1079
Cdd:cd00893    184 EYIEVLG--GVDSEL-FKEFRKLFLKGFMALRKHSDKILSLVEMMYSGHGITCFGKKTIQQLKQRFNPELTEGELEVYVL 260

                          250       260
                   ....*....|....*....|....*
gi 1207171262 1080 DQIEICRDKGWTVQFNWFLHLVLGI 1104
Cdd:cd00893    261 SLINKSLDNWRTRWYDKYQYFSQGI 285
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
 836-1104 6.79e-46

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: 166.89  E-value: 6.79e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  836 DTIGIIFKDGDDLRQDMLILQILLIMESIWELESLDLSLLPYGCISTGNKIGMIEIVKDATTIANIQQSTVGNTGafkde 915
Cdd:cd05168     29 DLRSVIVKSGDDLRQELLAMQLIKQFQRIFEEAGLPLWLRPYEILVTSSDSGLIETIPDTVSIDSLKKRFPNFTS----- 103

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  916 iLSQWLREKC--VNEDKHQQAVDRFVFSCGGYCVATYVLGIGDRHNDNIMITETGNLFHIDFGHILGNYKSflGISKERV 993
Cdd:cd05168    104 -LLDYFERTFgdPNSERFKEAQRNFVESLAAYSLVCYLLQIKDRHNGNILLDSEGHIIHIDFGFMLSNSPG--GLGFETA 180

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  994 PFVLTPDFLYLMGTTGkksSPNFLQFQNVCLKAYLALRHHTNLLIILFSMMLMTG-MPQLT--SKEDIEYIREALTVGRS 1070
Cdd:cd05168    181 PFKLTQEYVEVMGGLE---SDMFRYFKTLMIQGFLALRKHADRIVLLVEIMQQGSkLPCFFggGEFTIEQLRERFKLNLT 257

                          250       260       270
                   ....*....|....*....|....*....|....
gi 1207171262 1071 EDEAKQHFLDQIEICRDKGWTVQFNWFLHLVLGI 1104
Cdd:cd05168    258 EEECAQFVDSLIDKSLNNWRTRQYDNFQYLTNGI 291
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
840-1045 1.30e-34

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 144.54  E-value: 1.30e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  840 IIFKDGDDLRQDMLILQILLIMESIWELESLDLSLL----PYGCISTGNKIGMIEIVKDATTIANI-------------- 901
Cdd:COG5032   1799 FIVKGGDDLRQDELALQLIRLMNKILKKDKETRRRDlwirPYKVIPLSPGSGIIEWVPNSDTLHSIlreyhkrknisidq 1878

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  902 ----QQSTVGNTGAFKDE-----------ILSQWLREKCVNEDKHQQAVDRFVFSCGGYCVATYVLGIGDRHNDNIMITE 966
Cdd:COG5032   1879 ekklAARLDNLKLLLKDEfftkatlksppVLYDWFSESFPNPEDWLTARTNFARSLAVYSVIGYILGLGDRHPGNILIDR 1958

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  967 -TGNLFHIDFGHILGNYKSFLGIsKERVPFVLTPDFLYLMGTTGKKSSpnflqFQNVCLKAYLALRHHTNLLIILFSMML 1045
Cdd:COG5032   1959 sSGHVIHIDFGFILFNAPGRFPF-PEKVPFRLTRNIVEAMGVSGVEGS-----FRELCETAFRALRKNADSLMNVLELFV 2032
PI3Ka_III cd00870
Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is ...
 558-713 2.91e-30

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: 117.82  E-value: 2.91e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  558 PNHLRKQFEQIIATDPLHPLTSEDKELLWHFRQECMRDPKAYPKFLSSVKWG-KQEAvaitHYLLERSTIWDRsvLDVGL 636
Cdd:cd00870      7 NSKERKELNKILKYPPTTKLTDEEKDLIWKFRFYLTNNKKALTKFLKSVNWSdEQEV----KQALELMPKWAK--IDIED 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  637 VLQLLDCHFSDENVRTIAVRKLETLGDDDVLRYLLQLVQAVKFEPYH-------DSALARFLLKRALRSKRIGHFLFWFL 709
Cdd:cd00870     81 ALELLSPYFTNPVVRKYAVSRLKLASDEELLLYLLQLVQALKYENLDlsplprlDSPLADFLIERALKNPKLANFLYWYL 160


                   ....
gi 1207171262  710 RSEI 713
Cdd:cd00870    161 KVEL 164
C2_PI3K_like cd08380
C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes ...
 368-537 1.50e-29

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: 115.15  E-value: 1.50e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  368 ISLWDCNRKFRVKILGIDIPVLPRNSELIVFVEASIFHGQQLLAQERTSSK-PFTEEVIWNTWLEFNIKIKDLPKGARLS 446
Cdd:cd08380      1 KSLWDINFNLRIKIHGITNINLLDSEDLKLYVRVQLYHGGEPLCPPQSTKKvPFSTSVTWNEWLTFDILISDLPREARLC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  447 LQVsCGKAQTQTSKE-----TECKnksrllyyvnllLVDHRSLLRQGEFILHMWkmPEKSEDNSSvnadkLTSATNPDKN 521
Cdd:cd08380     81 LSI-YAVSEPGSKKEvplgwVNVP------------LFDYKGKLRQGMITLNLW--PGKKTDPRI-----ACTPCNNSNE 140

                          170
                   ....*....|....*.
gi 1207171262  522 NSMAVAILLDKYCYPV 537
Cdd:cd08380    141 NSTRLLIELPEFSKPV 156
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
 563-729 4.07e-29

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: 114.48  E-value: 4.07e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  563 KQFEQIIATDPLHPLTSEDKELLWHFRQECMRDPKAYPKFLSSVKWGKQEAVAITHYLLERstiWdrSVLDVGLVLQLLD 642
Cdd:cd00869      5 EKLLDLIQKQSTYTLSTEDKDLLWEKRLYCTNEPNALPLVLASAPSWDWANLMDVYQLLHQ---W--APLRPLIALELLL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  643 CHFSDENVRTIAVRKLETLGDDDVLRYLLQLVQAVKFEPYHDSALARFLLKRALRSKRIGHFLFWFLRSEIAQSmHYQQR 722
Cdd:cd00869     80 PKFPDQEVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALDDC-YFSSA 158


                   ....*..
gi 1207171262  723 YAVILEA 729
Cdd:cd00869    159 YQDLGAA 165
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 365-462 1.71e-25

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 101.65  E-value: 1.71e-25
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262   365 VFTISLWDCNRKFRVKILGIDIPVLPRNSELI-VFVEASIFHGQQLL-AQERTSSKPFTEEVIWNTWLEFNIKIKDLPKG 442
Cdd:smart00142    1 VKIESLWDCDRNLVITIALIHGIPLNWSRDYSdLYVEIQLYHGGKLLcLPVSTSYKPFFPSVKWNEWLTFPIQISDLPRE 80

                            90       100
                    ....*....|....*....|
gi 1207171262   443 ARLSLQVSCGKAQTQTSKET 462
Cdd:smart00142   81 ARLCITIYAVKNPSKGSEFG 100
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
 812-1045 3.84e-24

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


Pssm-ID: 270708 [Multi-domain]  Cd Length: 222  Bit Score: 101.96  E-value: 3.84e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  812 KVMASKKKPLWLQFKRADPTTLSsdtigIIFKDGDDLRQDMLILQIL----LIMESIWELESLDLSLLPYGCISTGNKIG 887
Cdd:cd05164      9 RILASLQKPKKITILGSDGKEYP-----FLVKGDDDLRKDERVMQLFqllnTLLEKDKETRKRNLTIRTYSVVPLSSQSG 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  888 MIEIVKDATTIANIqqstvgntgafkdeiLSQWLREKCVNEDKHQQAVDRFVFSCGGYCVATYVLGIGDRHNDNIMI-TE 966
Cdd:cd05164     84 LIEWVDNTTTLKPV---------------LKKWFNETFPDPTQWYEARSNYTKSTAVMSMVGYIIGLGDRHLENILIdTK 148

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1207171262  967 TGNLFHIDFGHILGNYKSFLgiSKERVPFVLTPDFLYLMGTTGKKSspnflQFQNVCLKAYLALRHHTNLLIILFSMML 1045
Cdd:cd05164    149 TGEVVHIDFGMIFNKGKTLP--VPEIVPFRLTRNIINGMGPTGVEG-----LFRKSCEQVLRVFRKHKDKLITFLDTFL 220
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 221-327 7.08e-24

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: 97.36  E-value: 7.08e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  221 TPMPEYLLsKISNNHILMVIHKE--TTSQTIKVSIDDTPVQVLQSFFAKitnKRALLGISEdvSESDFVLRVCGREEYLY 298
Cdd:pfam00794    3 TVSPEPLP-KLINNKLLISVHLEgdQMTKTFTCNPNSTPGSLIAQALTK---KLSVHTQGD--VTDDYVLKVCGRDEYLL 76

                           90       100
                   ....*....|....*....|....*....
gi 1207171262  299 GNNAIKDFHWIRQCLKNGEEIHLVLEHPP 327
Cdd:pfam00794   77 GDHPLGQFEYIRNCLKSGREPHLTLVEQS 105
PIKKc_DNA-PK cd05172
Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, ...
 809-1006 1.75e-22

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


Pssm-ID: 270716 [Multi-domain]  Cd Length: 235  Bit Score: 97.65  E-value: 1.75e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  809 EQCKVMASKKKPlwlqfKRAdpTTLSSDTIGIIF--KDGDDLRQDMLILQILLIMESIWEL----ESLDLSLLPYGCIST 882
Cdd:cd05172      6 PRVLVLSSKRRP-----KRI--TIRGSDEKEYKFlvKGGEDLRQDQRIQQLFDVMNNILASdpacRQRRLRIRTYQVIPM 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  883 GNKIGMIEIVKDATTIANIqqstvgntgaFKDEILSQWLREKCVNEDKHQQAVDRFVFSCGGYCVATYVLGIGDRHNDNI 962
Cdd:cd05172     79 TSRLGLIEWVDNTTPLKEI----------LENDLLRRALLSLASSPEAFLALRSNFARSLAAMSICGYILGIGDRHLSNF 148

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1207171262  963 MI-TETGNLFHIDFGHILGNYKSFLGISkERVPFVLTPDFLYLMG 1006
Cdd:cd05172    149 LVdLSTGRLIGIDFGHAFGSATQFLPIP-ELVPFRLTRQLLNLLQ 192
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 219-323 4.09e-22

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: 92.39  E-value: 4.09e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262   219 TTTPMPEYLLSKISNNHILMVIHKE--TTSQTIKVSIDDTPVQVLQSFFAKitnKRALLGiSEDVSESDFVLRVCGREEY 296
Cdd:smart00144    1 TSPSVPEPLPLKTIANKILIVVHLEkdQQTKTLKVNPNCTPDSVLAQAFTK---MLSLHD-QVDPTSEDYILKVCGRDEY 76

                            90       100
                    ....*....|....*....|....*..
gi 1207171262   297 LYGNNAIKDFHWIRQCLKNGEEIHLVL 323
Cdd:smart00144   77 LLGDHPLGSFEYIRNCLKNGTEPHLVL 103
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 368-533 1.34e-17

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: 81.59  E-value: 1.34e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  368 ISLWDCNRKFRVKILGI-DIPVLPRNSEliVFVEASIFHGQQLL-AQERTSSKPFTEEVIWNTWLEFNIKIKDLPKGARL 445
Cdd:cd08693      1 KSLWDIEEKFSITLHKIsNLNAAERTMK--VGVQAGLFHGGESLcKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARL 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  446 SLQV--SCGKAQTQTSKETECKNKSRLLYY----VNLLLVDHRSLLRQGEFILHMWKMPeksEDNSSVNADKL-TSATNP 518
Cdd:cd08693     79 CFAIyeVSKKAKGKRSRKNQTKKKKKKDDNpiawVNTMVFDYKGQLKTGDHTLYMWTYA---EDQSEDLLNPLgTVESNP 155

                          170
                   ....*....|....*
gi 1207171262  519 DKNNSMAVAILLDKY 533
Cdd:cd08693    156 NTESATALHISFPEY 170
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 809-1044 2.64e-15

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


Pssm-ID: 270625 [Multi-domain]  Cd Length: 237  Bit Score: 76.78  E-value: 2.64e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  809 EQCKVMASKKKPlwlqfKRAdpTTLSSDTIGIIF--KDGDDLRQDMLILQILLIMESIWELESLDLSLL----PYGCIST 882
Cdd:cd00892      6 DEVEIMPSLQKP-----KKI--TLVGSDGKKYPFlcKPKDDLRKDARMMEFNTLINRLLSKDPESRRRNlhirTYAVIPL 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  883 GNKIGMIEIVKDATTIANIQQStvgntgaFKDEILSQWLREKCVNEDKHQQAVDRFVFSCGGYCVATYVLGIGDRHNDNI 962
Cdd:cd00892     79 NEECGIIEWVPNTVTLRSILST-------LYPPVLHEWFLKNFPDPTAWYEARNNYTRSTAVMSMVGYILGLGDRHGENI 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  963 MI-TETGNLFHIDFGHILGNYKSfLGIsKERVPFVLTPDFLYLMGTTGKKSSpnflqFQNVCLKAYLALRHHTNLLI-IL 1040
Cdd:cd00892    152 LFdSTTGDVVHVDFDCLFDKGLT-LEV-PERVPFRLTQNMVDAMGVTGVEGT-----FRRTCEVTLRVLRENRETLMsVL 224


                   ....
gi 1207171262 1041 FSMM 1044
Cdd:cd00892    225 ETFV 228
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
 818-976 4.00e-14

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


Pssm-ID: 270870 [Multi-domain]  Cd Length: 136  Bit Score: 70.55  E-value: 4.00e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  818 KKPLWLQFKradpttlsSDTIGIIFKDGDD--------LRQDMLILQILLIMEsiwelesldlsLLPYGCIST----GNK 885
Cdd:cd13968      7 AKVFWAEGE--------CTTIGVAVKIGDDvnneegedLESEMDILRRLKGLE-----------LNIPKVLVTedvdGPN 67

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  886 IGMIEIVKDATTIANIQQstvgntgafkdeilsqwlrekcvnEDKHQQAVDRFVFSCGGYCVATYV--LGIGDRHNDNIM 963
Cdd:cd13968     68 ILLMELVKGGTLIAYTQE------------------------EELDEKDVESIMYQLAECMRLLHSfhLIHRDLNNDNIL 123

                          170
                   ....*....|...
gi 1207171262  964 ITETGNLFHIDFG 976
Cdd:cd13968    124 LSEDGNVKLIDFG 136
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
 841-1040 6.38e-13

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


Pssm-ID: 270715 [Multi-domain]  Cd Length: 282  Bit Score: 70.65  E-value: 6.38e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  841 IFKDGDDLRQDMLILQILLIMESIWELESLDLSLL----PYGCISTGNKIGMIEIVKDATTIANIQQSTVGNTGA----F 912
Cdd:cd05171     33 LVKGGDDLRQDAVMEQVFELVNQLLKRDKETRKRKlrirTYKVVPLSPRSGVLEFVENTIPLGEYLVGASSKSGAharyR 112

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  913 KDEILSQWLREKCV------NEDKHQ---------QAVDRFVF----SCGG--------YC--VAT-----YVLGIGDRH 958
Cdd:cd05171    113 PKDWTASTCRKKMRekakasAEERLKvfdeicknfKPVFRHFFlekfPDPSdwferrlaYTrsVATssivgYILGLGDRH 192

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  959 NDNIMI-TETGNLFHIDFGHILGNYKsFLGISkERVPFVLTPDFLYLMGTTGKKSspnflQFQNVCLKAYLALR-HHTNL 1036
Cdd:cd05171    193 LNNILIdQKTGELVHIDLGIAFEQGK-LLPIP-ETVPFRLTRDIVDGMGITGVEG-----VFRRCCEETLRVLReNKEAL 265


                   ....
gi 1207171262 1037 LIIL 1040
Cdd:cd05171    266 LTIL 269
C2_PI3K_class_I_alpha cd08398
C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 369-536 7.66e-12

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: 64.43  E-value: 7.66e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  369 SLWDCNRKFRVKIL-GIDIPVLPRNSeliVFVEASIFHGQQLLAQERTSSKPFTEEVIWNTWLEFNIKIKDLPKGARLSL 447
Cdd:cd08398      2 SLWKINSNLRIKILcATYVNVNDIDK---IYVRTGIYHGGEPLCDNVNTQRVPCSNPRWNEWLDYDIYIPDLPRSARLCL 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  448 QVsCGKAQTQTSKETECknksrLLYYVNLLLVDHRSLLRQGEFILHMWKMPEKSEDnsSVNADKLTsATNPDKNnsmAVA 527
Cdd:cd08398     79 SI-CSVKGRKGAKEEHC-----PLAWGNINLFDYTDTLVSGKMALNLWPVPHGLED--LLNPIGVT-GSNPNKD---TPC 146


                   ....*....
gi 1207171262  528 ILLDKYCYP 536
Cdd:cd08398    147 LELEFDRFS 155
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 397-495 1.05e-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: 60.46  E-value: 1.05e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  397 VFVEASIFHGQQLLAQ-ERTSSKPFTEEVI-WNTWLEFNIKIKDLPKGARLSLQVSCGKAQTQTSKETECKNKSrllyyv 474
Cdd:pfam00792    5 LYVECQLYHGGKPLCLpVSTRYVPFSNSSIkWNEWITFPIQISDLPRSARLCITIWDVSGPEKSFVPIGWVNTS------ 78

                           90       100
                   ....*....|....*....|.
gi 1207171262  475 nllLVDHRSLLRQGEFILHMW 495
Cdd:pfam00792   79 ---LFDKKGILRQGKQKLRLW 96
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 398-501 3.93e-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: 3.93e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  398 FVEASIFHGQQLLAQERTS-----SKPFTEEVIWNTWLEFNIKIKDLPKGARLSLQVScGKAQTQTSKETECKNKSRLLY 472
Cdd:cd04012     32 YLSCSLYHGGRLLCSPVTTkpvkiTKSFFPRVVWDEWIEFPIPVCQLPRESRLVLTLY-GTTSSPDGGSNKQRMGPEELG 110

                           90       100
                   ....*....|....*....|....*....
gi 1207171262  473 YVNLLLVDHRSLLRQGEFILHMWKMPEKS 501
Cdd:cd04012    111 WVSLPLFDFRGVLRQGSLLLGLWPPSKDN 139
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
 933-1009 1.61e-07

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


Pssm-ID: 270714  Cd Length: 304  Bit Score: 54.18  E-value: 1.61e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  933 QAVDRFVFSCGGYCVATYVLGIGDRHNDNIMIT-ETGNLFHIDF------GHILgnyksflgisK--ERVPFVLTPDFLY 1003
Cdd:cd05170    189 RVTQRFARSLAVMSMIGYIIGLGDRHLDNILVDlSTGEVVHIDYnvcfekGKRL----------RvpEKVPFRLTQNIEH 258


                   ....*.
gi 1207171262 1004 LMGTTG 1009
Cdd:cd05170    259 ALGPTG 264
C2_PI3K_class_III cd08397
C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 391-449 2.21e-07

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: 51.48  E-value: 2.21e-07
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207171262  391 RNSELivFVEASIFHGQQLLA-QERTSSKPFTEEVIWNTWLEFNIKIKDLPKGARLSLQV 449
Cdd:cd08397     28 PNSDL--FVTCQVFDDGKPLTlPVQTSYKPFKNRRNWNEWLTLPIKYSDLPRNSQLAITI 85
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 950-998 9.75e-07

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


Pssm-ID: 270713 [Multi-domain]  Cd Length: 279  Bit Score: 51.71  E-value: 9.75e-07
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1207171262  950 YVLGIGDRHNDNIMI-TETGNLFHIDFGhilgnyKSFLGISK-----ERVPFVLT 998
Cdd:cd05169    180 YILGLGDRHPSNIMLdRLTGKVIHIDFG------DCFEVAMHrekfpEKVPFRLT 228
PTZ00303 PTZ00303
phosphatidylinositol kinase; Provisional
 933-986 6.12e-03

phosphatidylinositol kinase; Provisional


Pssm-ID: 140324 [Multi-domain]  Cd Length: 1374  Bit Score: 40.84  E-value: 6.12e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1207171262  933 QAVDRFVFSCGGYCVATYVLGIGDRHNDNIMITETGNLFHIDFGHILGNyKSFL 986
Cdd:PTZ00303  1128 RSCINFLASAKLFLLLNYIFSIGDRHKGNVLIGTNGALLHIDFRFIFSE-KTFV 1180
 
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.
Help | Disclaimer | Write to the Help Desk
NCBI | NLM | NIH