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Conserved domains on  [gi|1046901447|ref|XP_017451432|]
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phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform X1 [Rattus norvegicus]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 706-1067 0e+00

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: 784.15  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  706 MKVLSKQVEALNKLKTLNSLIKLNAMKLNRAKGKEAMHTCLKQSAYREALSDLQSPLNPCVILSELYVEKCRYMDSKMKP 785
Cdd:cd05173      1 MKVLSKQVEALNKLKTLNSLIKLNAVKLSKAKGKEAMHTCLRQSAYREALSDLQSPLNPSIILSELNVEKCKYMDSKMKP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  786 LWLVYSNRAFGEDAVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIQL 865
Cdd:cd05173     81 LWIVYNNKLFGGDSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVPYGCLATGDRSGLIEVVSSAETIADIQL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  866 NSSNVAATAAFNKDALLNWLKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNF 945
Cdd:cd05173    161 NSSNVAAAAAFNKDALLNWLKEYNSGDDLERAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGNF 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  946 KSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYLK 1025
Cdd:cd05173    241 KSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQYCEDAYLILRKNGNLFITLFALMLTAGLPELTSVKDIQYLK 320

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|..
gi 1046901447 1026 DSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTVRKD 1067
Cdd:cd05173    321 DSLALGKSEEEALKQFRQKFDEALRESWTTKVNWMAHTVRKD 362
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 532-702 2.95e-95

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: 299.61  E-value: 2.95e-95
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  532 KKFLAVLKEILDRDPLSQLCENEMDLIWTLRQDCReNFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLD 611
Cdd:cd00872      1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECR-KKPQALPKLLLSVKWNKRDDVAQMYQLLKRWPKLKPEQALELLD 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  612 FNYPDQYVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALDNRRIGQFLFWHLRSEVHTPAVSIQF 691
Cdd:cd00872     80 CNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVSQRF 159

                          170
                   ....*....|.
gi 1046901447  692 GVILEAYCRGS 702
Cdd:cd00872    160 GLLLEAYLRGC 170
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 324-501 1.04e-89

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: 284.59  E-value: 1.04e-89
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  324 SHVWDNNNPFQIVLVKGNKLNT-EETVKVHVRAGLFHGTELLCKTVVSSEISGKNDHIWNEQLEFDINICDLPRMARLCF 402
Cdd:cd08693      1 KSLWDIEEKFSITLHKISNLNAaERTMKVGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  403 AVYAVLDKVKTkkstktINPSKYQTIRKAGKVHYPVAWVNTMVFDFKGQLRSGDVILHSWSSFPDELEEMLNPMGTVQTN 482
Cdd:cd08693     81 AIYEVSKKAKG------KRSRKNQTKKKKKKDDNPIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESN 154

                          170
                   ....*....|....*....
gi 1046901447  483 PYAENATALHIKFPENKKQ 501
Cdd:cd08693    155 PNTESATALHISFPEYKPE 173
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 180-288 1.42e-41

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: 147.86  E-value: 1.42e-41
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447   180 HEPSVLENLEDKLYGGKLVVAVHFENSQDVFSFQVSPNLNPIKINELAIQKRLTIRGKEEEASPcDYVLQVSGRVEYVFG 259
Cdd:smart00144    1 TSPSVPEPLPLKTIANKILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQVDPTSE-DYILKVCGRDEYLLG 79

                            90       100
                    ....*....|....*....|....*....
gi 1046901447   260 DHPLIQFQYIRNCVMNRTLPHFILVECCK 288
Cdd:smart00144   80 DHPLGSFEYIRNCLKNGTEPHLVLMTLSA 108
PI3K_p85B smart00143
PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.
 41-118 3.99e-37

PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.


:

Pssm-ID: 197539  Cd Length: 78  Bit Score: 133.76  E-value: 3.99e-37
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1046901447    41 YIQLEVPREATISYIKQMLWKQVHNYPMFNLLMDIDSYMFACVNQTAVYEELEDETRRLCDVRPFLPVLKLVTRSCDP 118
Cdd:smart00143    1 LVTLRVLREATLSTIKHELFKQARKMPLGQLLQDESSYIFVSVNQTAEIEEFFDETRRLSDLRLFFPFLKLIEPVGNR 78
 
Name Accession Description Interval E-value
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 706-1067 0e+00

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: 784.15  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  706 MKVLSKQVEALNKLKTLNSLIKLNAMKLNRAKGKEAMHTCLKQSAYREALSDLQSPLNPCVILSELYVEKCRYMDSKMKP 785
Cdd:cd05173      1 MKVLSKQVEALNKLKTLNSLIKLNAVKLSKAKGKEAMHTCLRQSAYREALSDLQSPLNPSIILSELNVEKCKYMDSKMKP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  786 LWLVYSNRAFGEDAVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIQL 865
Cdd:cd05173     81 LWIVYNNKLFGGDSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVPYGCLATGDRSGLIEVVSSAETIADIQL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  866 NSSNVAATAAFNKDALLNWLKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNF 945
Cdd:cd05173    161 NSSNVAAAAAFNKDALLNWLKEYNSGDDLERAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGNF 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  946 KSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYLK 1025
Cdd:cd05173    241 KSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQYCEDAYLILRKNGNLFITLFALMLTAGLPELTSVKDIQYLK 320

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|..
gi 1046901447 1026 DSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTVRKD 1067
Cdd:cd05173    321 DSLALGKSEEEALKQFRQKFDEALRESWTTKVNWMAHTVRKD 362
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 532-702 2.95e-95

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: 299.61  E-value: 2.95e-95
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  532 KKFLAVLKEILDRDPLSQLCENEMDLIWTLRQDCReNFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLD 611
Cdd:cd00872      1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECR-KKPQALPKLLLSVKWNKRDDVAQMYQLLKRWPKLKPEQALELLD 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  612 FNYPDQYVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALDNRRIGQFLFWHLRSEVHTPAVSIQF 691
Cdd:cd00872     80 CNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVSQRF 159

                          170
                   ....*....|.
gi 1046901447  692 GVILEAYCRGS 702
Cdd:cd00872    160 GLLLEAYLRGC 170
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 324-501 1.04e-89

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: 284.59  E-value: 1.04e-89
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  324 SHVWDNNNPFQIVLVKGNKLNT-EETVKVHVRAGLFHGTELLCKTVVSSEISGKNDHIWNEQLEFDINICDLPRMARLCF 402
Cdd:cd08693      1 KSLWDIEEKFSITLHKISNLNAaERTMKVGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  403 AVYAVLDKVKTkkstktINPSKYQTIRKAGKVHYPVAWVNTMVFDFKGQLRSGDVILHSWSSFPDELEEMLNPMGTVQTN 482
Cdd:cd08693     81 AIYEVSKKAKG------KRSRKNQTKKKKKKDDNPIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESN 154

                          170
                   ....*....|....*....
gi 1046901447  483 PYAENATALHIKFPENKKQ 501
Cdd:cd08693    155 PNTESATALHISFPEYKPE 173
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 538-711 4.06e-82

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: 264.50  E-value: 4.06e-82
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447   538 LKEILDRDPLSQLCENEMDLIWTLRQDCRENFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLDFNYPDQ 617
Cdd:smart00145   11 LEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPKALPKFLLSVKWSDADEVAQALSLLLSWAPLDPEDALELLDPKFPDP 90

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447   618 YVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALDNRRIGQFLFWHLRSEVHTPAVSIQFGVILEA 697
Cdd:smart00145   91 FVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHVSIRFGLLLEA 170

                           170
                    ....*....|....
gi 1046901447   698 YCRGSVGHMKVLSK 711
Cdd:smart00145  171 YLRGCGTHLKELLK 184
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 802-1019 1.34e-81

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: 265.32  E-value: 1.34e-81
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447   802 VIFKNGDDLRQDMLTLQMLRLMDLLWKE----AGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIQLNS---------- 867
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKdketRRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447   868 ------------SNVAATAAFNKDALLNWLKEYNSGDDLD--RAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQL 933
Cdd:smart00146   81 rsqtatrlkkleLFLEATGKFPDPVLYDWFTKKFPDPSEDyfEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447   934 FHIDFGHILGNFKSKFGIKrERVPFILTYDFIHVIqqgktGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLP 1013
Cdd:smart00146  161 FHIDFGFILGNGPKLFGFP-ERVPFRLTPEMVDVM-----GDSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLP 234


                    ....*.
gi 1046901447  1014 ELTSVK 1019
Cdd:smart00146  235 DWRSGK 240
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 526-711 1.82e-81

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: 263.04  E-value: 1.82e-81
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  526 VSSRGGKKFLAVLKEILDRDPLSQLCENEMDLIWTLRqDCRENFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPRE 605
Cdd:pfam00613    1 KDLKPNEKERKELEAILAYDPLSKLTAEEKDLIWKFR-YYLMLVPKALTKLLLSVKWSDLSEVAEALSLLLKWAPIDPVD 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  606 ALELLDFNYPDQYVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALDNRRIGQFLFWHLRSEVHTP 685
Cdd:pfam00613   80 ALELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEIHDE 159

                          170       180
                   ....*....|....*....|....*.
gi 1046901447  686 AVSIQFGVILEAYCRGSVGHMKVLSK 711
Cdd:pfam00613  160 EVSPRFGSLLELYLRSCGTSLLGLNK 185
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 800-1017 2.99e-76

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: 250.71  E-value: 2.99e-76
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  800 VGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDL-RMLPYGCLATGDRSGLIEVVSTSETIADIQLN--SSNVAATAAF 876
Cdd:pfam00454    2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEygENGVPPTAMV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  877 N-----------------------KDALLNWLKEYN-SGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKK-TG 931
Cdd:pfam00454   82 KilhsalnypklklefesrislppKVGLLQWFVKKSpDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVDKtTG 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  932 QLFHIDFGHILGNFKSKFGIKrERVPFILTYDFIHVIqqgktGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAG 1011
Cdd:pfam00454  162 KLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAM-----GPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVADG 235


                   ....*.
gi 1046901447 1012 LPELTS 1017
Cdd:pfam00454  236 LPDWSI 241
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 180-288 1.42e-41

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: 147.86  E-value: 1.42e-41
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447   180 HEPSVLENLEDKLYGGKLVVAVHFENSQDVFSFQVSPNLNPIKINELAIQKRLTIRGKEEEASPcDYVLQVSGRVEYVFG 259
Cdd:smart00144    1 TSPSVPEPLPLKTIANKILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQVDPTSE-DYILKVCGRDEYLLG 79

                            90       100
                    ....*....|....*....|....*....
gi 1046901447   260 DHPLIQFQYIRNCVMNRTLPHFILVECCK 288
Cdd:smart00144   80 DHPLGSFEYIRNCLKNGTEPHLVLMTLSA 108
PI3K_p85B smart00143
PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.
 41-118 3.99e-37

PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.


Pssm-ID: 197539  Cd Length: 78  Bit Score: 133.76  E-value: 3.99e-37
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1046901447    41 YIQLEVPREATISYIKQMLWKQVHNYPMFNLLMDIDSYMFACVNQTAVYEELEDETRRLCDVRPFLPVLKLVTRSCDP 118
Cdd:smart00143    1 LVTLRVLREATLSTIKHELFKQARKMPLGQLLQDESSYIFVSVNQTAEIEEFFDETRRLSDLRLFFPFLKLIEPVGNR 78
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
707-1054 4.23e-34

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 142.61  E-value: 4.23e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  707 KVLSKQVEALNK-----LKTLNSLIKLNAMKLNRAKGKEAMHTCLKQsAYREALSDLQSPLNPCVILSELYVEKCRYMDS 781
Cdd:COG5032   1701 KKFKIDISLLNLsrklyISVLRSIRKRLKRLLELRLKKVSPKLLLFH-AFLEIKLPGQYLLDKPFVLIERFEPEVSVVKS 1779

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  782 -KMKP--LWLVYSNrafGEDaVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGL----DLRMLPYGCLATGDRSGLIEVV 854
Cdd:COG5032   1780 hLQRPrrLTIRGSD---GKL-YSFIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGIIEWV 1855

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  855 STSETIADI------QLN-SSNVAATAAFNKDALLNWLKEY-------------------NSGDDLD--RAIEEFTLSCA 906
Cdd:COG5032   1856 PNSDTLHSIlreyhkRKNiSIDQEKKLAARLDNLKLLLKDEfftkatlksppvlydwfseSFPNPEDwlTARTNFARSLA 1935

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  907 GYCVASYVLGIGDRHSDNIMV-KKTGQLFHIDFGHILGNFKSKFGIKrERVPFILTYDFIHVIqqGKTGnTEkfGRFRQC 985
Cdd:COG5032   1936 VYSVIGYILGLGDRHPGNILIdRSSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAM--GVSG-VE--GSFREL 2009

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  986 CEDAYLILRRHGNLFITLFALMLT------AGLPE--LTSVKDIQYLKDSLALGKSEEEALKQFK---QKFDEALRESWT 1054
Cdd:COG5032   2010 CETAFRALRKNADSLMNVLELFVRdpliewRRLPCfrEIQNNEIVNVLERFRLKLSEKDAEKFVDlliNKSVESLITQAT 2089
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 180-288 5.99e-33

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: 123.17  E-value: 5.99e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  180 HEPSVLENLEdKLYGGKLVVAVHFENSQDVFSFQVSPNLNPIKINELAIQKRLTIRGKEEEASpcDYVLQVSGRVEYVFG 259
Cdd:pfam00794    1 ASTVSPEPLP-KLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVTD--DYVLKVCGRDEYLLG 77

                           90       100
                   ....*....|....*....|....*....
gi 1046901447  260 DHPLIQFQYIRNCVMNRTLPHFILVECCK 288
Cdd:pfam00794   78 DHPLGQFEYIRNCLKSGREPHLTLVEQSS 106
PI3K_p85B pfam02192
PI3-kinase family, p85-binding domain;
44-117 1.38e-31

PI3-kinase family, p85-binding domain;


Pssm-ID: 460483  Cd Length: 74  Bit Score: 118.00  E-value: 1.38e-31
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1046901447   44 LEVPREATISYIKQMLWKQVHNYPMFNLLMDIDSYMFACVNQTAVYEELEDETRRLCDVRPFLPVLKLVTRSCD 117
Cdd:pfam02192    1 LRVSRNATLSEIKEELWEEAKKYPLYYLLKDPQSYVFTCINQTAEIEELYDETRRLCDVRPFFPILKLVEREGD 74
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 321-409 1.39e-27

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 107.43  E-value: 1.39e-27
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447   321 RVISHVWDNNNPFQ--IVLVKGNKLNTEETV-KVHVRAGLFHGTELLCKTVVSSEISGKNDHIWNEQLEFDINICDLPRM 397
Cdd:smart00142    1 VKIESLWDCDRNLVitIALIHGIPLNWSRDYsDLYVEIQLYHGGKLLCLPVSTSYKPFFPSVKWNEWLTFPIQISDLPRE 80

                            90
                    ....*....|..
gi 1046901447   398 ARLCFAVYAVLD 409
Cdd:smart00142   81 ARLCITIYAVKN 92
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 350-471 7.35e-19

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: 83.96  E-value: 7.35e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  350 KVHVRAGLFHGTELLCKTVVSSEISGKNDHI-WNEQLEFDINICDLPRMARLCFAVYAVLDkvktkkstktinpskyqti 428
Cdd:pfam00792    4 DLYVECQLYHGGKPLCLPVSTRYVPFSNSSIkWNEWITFPIQISDLPRSARLCITIWDVSG------------------- 64

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1046901447  429 rkAGKVHYPVAWVNTMVFDFKGQLRSGDVILHSWSSFPDELEE 471
Cdd:pfam00792   65 --PEKSFVPIGWVNTSLFDKKGILRQGKQKLRLWPSKSTPGRS 105
 
Name Accession Description Interval E-value
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 706-1067 0e+00

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: 784.15  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  706 MKVLSKQVEALNKLKTLNSLIKLNAMKLNRAKGKEAMHTCLKQSAYREALSDLQSPLNPCVILSELYVEKCRYMDSKMKP 785
Cdd:cd05173      1 MKVLSKQVEALNKLKTLNSLIKLNAVKLSKAKGKEAMHTCLRQSAYREALSDLQSPLNPSIILSELNVEKCKYMDSKMKP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  786 LWLVYSNRAFGEDAVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIQL 865
Cdd:cd05173     81 LWIVYNNKLFGGDSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVPYGCLATGDRSGLIEVVSSAETIADIQL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  866 NSSNVAATAAFNKDALLNWLKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNF 945
Cdd:cd05173    161 NSSNVAAAAAFNKDALLNWLKEYNSGDDLERAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGNF 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  946 KSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYLK 1025
Cdd:cd05173    241 KSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQYCEDAYLILRKNGNLFITLFALMLTAGLPELTSVKDIQYLK 320

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|..
gi 1046901447 1026 DSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTVRKD 1067
Cdd:cd05173    321 DSLALGKSEEEALKQFRQKFDEALRESWTTKVNWMAHTVRKD 362
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 706-1066 0e+00

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


Pssm-ID: 270709 [Multi-domain]  Cd Length: 363  Bit Score: 653.55  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  706 MKVLSKQVEALNKLKTLNSLIKlnAMKLNRAKGKEAMHTCLKQSAYREALSDLQSPLNPCVILSELYVEKCRYMDSKMKP 785
Cdd:cd05165      1 LKSLSRQVEALNKLKKLSDILK--EKKKSKEKVKKLLKECLKQKFYDEALQNFQSPLNPSHKLGELIIEKCKVMDSKKRP 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  786 LWLVYSNR---AFGEDAVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIAD 862
Cdd:cd05165     79 LWLVFENAdplALSGEDIKIIFKNGDDLRQDMLTLQIIRIMDNIWKEEGLDLRMLPYGCLSTGDNVGLIEVVRNAKTIAN 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  863 IQLNSSNVAaTAAFNKDALLNWLKEYN-SGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHI 941
Cdd:cd05165    159 IQKKKGKVA-TLAFNKDSLHKWLKEKNkTGEKYDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVKENGQLFHIDFGHF 237

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  942 LGNFKSKFGIKRERVPFILTYDFIHVIQQGKTG-NTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKD 1020
Cdd:cd05165    238 LGNFKKKFGIKRERVPFVLTHDFVYVIARGQDNtKSEEFQEFQELCEKAYLILRRHGNLFISLFSMMLSTGIPELTSVKD 317

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*.
gi 1046901447 1021 IQYLKDSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTVRK 1066
Cdd:cd05165    318 IEYLRKTLALDKTEEEALKYFRKKFNEALKGSWTTKVNWFFHNVKH 363
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 705-1067 0e+00

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: 651.73  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  705 HMKVLSKQVEALNKLKTLNSLIKLNAMKLNRAKGKEAMHTCLKQSAYREALSDLQSPLNPCVILSELYVEKCRYMDSKMK 784
Cdd:cd05174      3 HMKVLMKQGEALSKMKALNDFVKVSSQKATKPQTKEMMHVCMKQETYMEALSHLQSPLDPSIILEEVCVDQCTFMDSKMK 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  785 PLWLVYSNRAFGEDAVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIQ 864
Cdd:cd05174     83 PLWIMYSSEEAGAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTIANIQ 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  865 LNSSNVAATAAFNKDALLNWLKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGN 944
Cdd:cd05174    163 LNKSNMAATAAFNKDALLNWLKSKNPGDALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGN 242

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  945 FKSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYL 1024
Cdd:cd05174    243 FKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCSKDIQYL 322

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|...
gi 1046901447 1025 KDSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTVRKD 1067
Cdd:cd05174    323 KDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKD 365
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 706-1050 1.19e-160

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: 477.83  E-value: 1.19e-160
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  706 MKVLSKQVEALNKLKTLNSLIKlnamKLNRAKGKEAMHTCLKQSAYREALsdlQSPLNPCVILSELYVEKCRYMDSKMKP 785
Cdd:cd00891      1 REELLKQVKVLDELKEIAKKIK----EEPSEERKEVLEKLLQKLELPKKF---TLPLDPRMEVKGLIVEKCKVMDSKKLP 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  786 LWLVYSNRAFGEDAVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIQl 865
Cdd:cd00891     74 LWLVFKNADPGGDPIKVIFKAGDDLRQDQLTLQLLRIMDKLWKKEGLDLRMTPYKCIATGDEVGMIEVVPNSETTAAIQ- 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  866 nSSNVAATAAFNKDALLNWLKEYN-SGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGN 944
Cdd:cd00891    153 -KKYGGFGAAFKDTPISNWLKKHNpTEEEYEEAVENFIRSCAGYCVATYVLGIGDRHNDNIMVTKSGHLFHIDFGHFLGN 231

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  945 FKSKFGIKRERVPFILTYDFIHVIqqgKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYL 1024
Cdd:cd00891    232 FKKKFGIKRERAPFVFTPEMAYVM---GGEDSENFQKFEDLCCKAYNILRKHGNLLINLFSLMLSAGIPELQSIEDIEYL 308

                          330       340
                   ....*....|....*....|....*.
gi 1046901447 1025 KDSLALGKSEEEALKQFKQKFDEALR 1050
Cdd:cd00891    309 RDALQLDLSDEEAAEHFRKLIHESLN 334
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 709-1064 9.30e-117

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: 363.92  E-value: 9.30e-117
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  709 LSKQVEALNKLKTLnsliklnAMKLNRAKGKEamhtclKQSAYREALSDLQS---------PLNPCVILSELYVEKCRYM 779
Cdd:cd05166      4 FLKQHVLVQALTSI-------AEKVKSAKDSA------RENALRRELEQLASfllensfrlPLDPALEVTGVDVRSCSYF 70

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  780 DSKMKPLWLVYSNRAFGEDAVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSET 859
Cdd:cd05166     71 NSNALPLKLVFRNADPRAEPISVIFKVGDDLRQDMLTLQLIRIMDKIWLQEGLDLKMITFRCVPTGNKRGMVELVPEAET 150

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  860 IADIQlnsSNVAATAAFNKDALLNWLKEYNSG-DDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDF 938
Cdd:cd05166    151 LREIQ---TEHGLTGSFKDRPLADWLQKHNPSeLEYEKAVENFIRSCAGYCVATYVLGICDRHNDNIMLKTSGHLFHIDF 227

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  939 GHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTgNTEKFGRF-RQCCEdAYLILRRHGNLFITLFALMLTAGLPELTS 1017
Cdd:cd05166    228 GKFLGDAQMFGNFKRDRVPFVLTSDMAYVINGGDK-PSSRFQLFvDLCCQ-AFNIIRKNSNLLLNLLSLMLSSGIPGVTQ 305

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*..
gi 1046901447 1018 vKDIQYLKDSLALGKSEEEALKQFKQKFDEALReSWTTKVNWMAHTV 1064
Cdd:cd05166    306 -DDLRYVQDALLPELTDAEATAHFTRMIEESLS-SKFTQLNFFIHNL 350
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 756-1064 1.50e-112

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: 353.40  E-value: 1.50e-112
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  756 SDLQSPLNPCVILSELYVEKCRYMDSKMKPLWLVYS---NRAFGEDAVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGL 832
Cdd:cd00894     53 ESFRVPYDPGLRAGALVIEKCKVMASKKKPLWLEFKcadPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESL 132

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  833 DLRMLPYGCLATGDRSGLIEVVSTSETIADIQlnSSNVAATAAFNKDALLNWLKEYNSGDD-LDRAIEEFTLSCAGYCVA 911
Cdd:cd00894    133 DLCLLPYGCISTGDKIGMIEIVKDATTIAKIQ--QSTVGNTGAFKDEVLNHWLKEKCPIEEkFQAAVERFVYSCAGYCVA 210

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  912 SYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQCCEDAYL 991
Cdd:cd00894    211 TFVLGIGDRHNDNIMITETGNLFHIDFGHILGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSLHFQKFQDVCVKAYL 290

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1046901447  992 ILRRHGNLFITLFALMLTAGLPELTSVKDIQYLKDSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTV 1064
Cdd:cd00894    291 ALRHHTNLLIILFSMMLMTGMPQLTSKEDIEYIRDALTVGKSEEDAKKHFLDQIEVCRDKGWTVQFNWFLHLV 363
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 705-1066 9.80e-111

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: 348.59  E-value: 9.80e-111
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  705 HMKVLSKQVEALNKLKTLNSLIKLNAMKLNRAKGKEAMHTCLKQSAYREALSDLQSPLNPCVILSELYVEKCRYMDSKMK 784
Cdd:cd05175      4 YLKHLSRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKR 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  785 PLWLVYSNRAFGEDAV----GVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETI 860
Cdd:cd05175     84 PLWLNWENPDIMSELLfqnnEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHTI 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  861 ADIQLNSSnVAATAAFNKDALLNWLKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGH 940
Cdd:cd05175    164 MQIQCKGG-LKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGH 242

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  941 ILGNFKSKFGIKRERVPFILTYDFIHVIQQG--KTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSV 1018
Cdd:cd05175    243 FLDHKKKKFGYKRERVPFVLTQDFLIVISKGaqECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSF 322

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*...
gi 1046901447 1019 KDIQYLKDSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTVRK 1066
Cdd:cd05175    323 DDIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQ 370
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 532-702 2.95e-95

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: 299.61  E-value: 2.95e-95
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  532 KKFLAVLKEILDRDPLSQLCENEMDLIWTLRQDCReNFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLD 611
Cdd:cd00872      1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECR-KKPQALPKLLLSVKWNKRDDVAQMYQLLKRWPKLKPEQALELLD 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  612 FNYPDQYVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALDNRRIGQFLFWHLRSEVHTPAVSIQF 691
Cdd:cd00872     80 CNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVSQRF 159

                          170
                   ....*....|.
gi 1046901447  692 GVILEAYCRGS 702
Cdd:cd00872    160 GLLLEAYLRGC 170
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 324-501 1.04e-89

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: 284.59  E-value: 1.04e-89
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  324 SHVWDNNNPFQIVLVKGNKLNT-EETVKVHVRAGLFHGTELLCKTVVSSEISGKNDHIWNEQLEFDINICDLPRMARLCF 402
Cdd:cd08693      1 KSLWDIEEKFSITLHKISNLNAaERTMKVGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCF 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  403 AVYAVLDKVKTkkstktINPSKYQTIRKAGKVHYPVAWVNTMVFDFKGQLRSGDVILHSWSSFPDELEEMLNPMGTVQTN 482
Cdd:cd08693     81 AIYEVSKKAKG------KRSRKNQTKKKKKKDDNPIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESN 154

                          170
                   ....*....|....*....
gi 1046901447  483 PYAENATALHIKFPENKKQ 501
Cdd:cd08693    155 PNTESATALHISFPEYKPE 173
PI3Kc_C2_alpha cd05176
Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 714-1064 2.25e-84

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: 277.25  E-value: 2.25e-84
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  714 EALNKLKTLNSLIKLNAMKLNRAKGKeamhtcLKQSAYREALSDLQS---------PLNPCVILSELYVEKCRYMDSKMK 784
Cdd:cd05176      2 EELEKQTRLVQLLGRVAEKVRQASGS------ARQVALQDGMERVQSffqknkcrlPLSPSLVAKELNIKACSFFSSNAV 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  785 PLWLVYSNR-AFGEDaVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIADI 863
Cdd:cd05176     76 PLKVALVNAdPLGEE-INVMFKVGEDLRQDMLALQMIKIMDKIWLQEGLDLRMVIFKCLSTGKDRGMVELVPSSDTLRKI 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  864 QLNssnVAATAAFNKDALLNWLKEYN-SGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHIL 942
Cdd:cd05176    155 QVE---YGVTGSFKDKPLAEWLRKYNpSEEEYEKASENFIYSCAGCCVATYVLGICDRHNDNIMLRSTGHMFHIDFGKFL 231

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  943 GNFKSKFGIKRERVPFILTYDFIHVIQQGKTgNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQ 1022
Cdd:cd05176    232 GHAQMFGSFKRDRAPFVLTSDMAYVINGGEK-PTIRFQLFVDLCCQAYNLIRKHTNLFLNLLSLMLSSGLPELTGIQDLK 310

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|..
gi 1046901447 1023 YLKDSLALGKSEEEALKQFKQKFDEALrESWTTKVNWMAHTV 1064
Cdd:cd05176    311 YVFDALQPQTTDAEATIFFTRLIESSL-GSVATKFNFFIHNL 351
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 538-711 4.06e-82

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: 264.50  E-value: 4.06e-82
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447   538 LKEILDRDPLSQLCENEMDLIWTLRQDCRENFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLDFNYPDQ 617
Cdd:smart00145   11 LEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPKALPKFLLSVKWSDADEVAQALSLLLSWAPLDPEDALELLDPKFPDP 90

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447   618 YVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALDNRRIGQFLFWHLRSEVHTPAVSIQFGVILEA 697
Cdd:smart00145   91 FVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHVSIRFGLLLEA 170

                           170
                    ....*....|....
gi 1046901447   698 YCRGSVGHMKVLSK 711
Cdd:smart00145  171 YLRGCGTHLKELLK 184
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 802-1019 1.34e-81

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: 265.32  E-value: 1.34e-81
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447   802 VIFKNGDDLRQDMLTLQMLRLMDLLWKE----AGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIQLNS---------- 867
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKdketRRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447   868 ------------SNVAATAAFNKDALLNWLKEYNSGDDLD--RAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQL 933
Cdd:smart00146   81 rsqtatrlkkleLFLEATGKFPDPVLYDWFTKKFPDPSEDyfEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447   934 FHIDFGHILGNFKSKFGIKrERVPFILTYDFIHVIqqgktGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLP 1013
Cdd:smart00146  161 FHIDFGFILGNGPKLFGFP-ERVPFRLTPEMVDVM-----GDSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLP 234


                    ....*.
gi 1046901447  1014 ELTSVK 1019
Cdd:smart00146  235 DWRSGK 240
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 526-711 1.82e-81

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: 263.04  E-value: 1.82e-81
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  526 VSSRGGKKFLAVLKEILDRDPLSQLCENEMDLIWTLRqDCRENFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPRE 605
Cdd:pfam00613    1 KDLKPNEKERKELEAILAYDPLSKLTAEEKDLIWKFR-YYLMLVPKALTKLLLSVKWSDLSEVAEALSLLLKWAPIDPVD 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  606 ALELLDFNYPDQYVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALDNRRIGQFLFWHLRSEVHTP 685
Cdd:pfam00613   80 ALELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEIHDE 159

                          170       180
                   ....*....|....*....|....*.
gi 1046901447  686 AVSIQFGVILEAYCRGSVGHMKVLSK 711
Cdd:pfam00613  160 EVSPRFGSLLELYLRSCGTSLLGLNK 185
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 707-1049 6.79e-79

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: 262.08  E-value: 6.79e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  707 KVLSKQVEALNKLKTLNSLIKlnAMKLNRAKGKEAMHTCLKQSAYREALSD--LQSPLNPCVILSELYVEKCRYMDSKMK 784
Cdd:cd00896      2 EALKRQQEFVDRLRSLMKEVK--NEKGSRDKKIERLRELLSDSELGLLLFFepLPLPLDPSVKVTGIIPEKSTVFKSALM 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  785 PLWLVYSNRAFGEdaVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIq 864
Cdd:cd00896     80 PLKLTFKTLDGGE--YKVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVPNSKALADI- 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  865 LNssnvaataafNKDALLNWLKEYNsGDDLDR------AIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDF 938
Cdd:cd00896    157 LK----------KYGSILNFLRKHN-PDESGPygikpeVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHIDF 225

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  939 GHILGN----FKSKFGIKRERVPFIltydfihviqqGKTgNTEKFGRFRQ-CCEdAYLILRRHGNLFITLFALMLTAGLP 1013
Cdd:cd00896    226 GYILGRdpkpFPPPMKLCKEMVEAM-----------GGA-NSEGYKEFKKyCCT-AYNILRKHANLILNLFSLMVDANIP 292

                          330       340       350
                   ....*....|....*....|....*....|....*...
gi 1046901447 1014 ELTSVKD--IQYLKDSLALGKSEEEALKQFKQKFDEAL 1049
Cdd:cd00896    293 DIALEPDkaVLKVQEKFRLDLSDEEAEQYFQNLIDESV 330
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 761-1064 3.16e-78

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: 260.59  E-value: 3.16e-78
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  761 PLNPCVILSELYVEKCRYMDSKMKPLWLVYSNRAFGEDAVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYG 840
Cdd:cd05177     53 PLNPALRVKGIDADACSYFTSNAAPLKISFINANPLAKNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYR 132

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  841 CLATGDRSGLIEVVSTSETIADIQLNSsnvAATAAFNKDALLNWLKEYN-SGDDLDRAIEEFTLSCAGYCVASYVLGIGD 919
Cdd:cd05177    133 CLSTGKTQGLVQMVPDAVTLAKIHRES---GLIGPLKENTIEKWFHMHNkLKEDYDKAVRNFFHSCAGWCVVTFILGVCD 209

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  920 RHSDNIMVKKTGQLFHIDFGHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTgNTEKFGRFRQCCEDAYLILRRHGNL 999
Cdd:cd05177    210 RHNDNIMLTHSGHMFHIDFGKFLGHAQTFGSIKRDRAPFIFTSEMEYFITEGGK-KPQRFQRFVELCCRAYNIVRKHSQL 288

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1046901447 1000 FITLFALMLTAGLPELTSVKDIQYLKDSLALGKSEEEALKQFKQKFDEALrESWTTKVNWMAHTV 1064
Cdd:cd05177    289 LLNLLEMMLHAGLPELKDIQDLKYVYNNLRPQDTDLEATSYFTKKIKESL-ECFPVKLNNLIHTL 352
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 747-1064 2.69e-76

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: 255.31  E-value: 2.69e-76
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  747 KQSAYREALSDLQS----------PLNPCVILSELYVEKCRYMDSKMKPLWLVYSNRAFGEDAVGVIFKNGDDLRQDMLT 816
Cdd:cd00895     29 RQGILREGLEEVKQffsingscrlPLSPSLLVKGIVPRDCSYFNSNAVPLKLSFQNVDPLGENIRVIFKCGDDLRQDMLT 108

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  817 LQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIQLNSsnvAATAAFNKDALLNWLKEYNSG-DDLD 895
Cdd:cd00895    109 LQMIRIMNKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEH---GVTGSFKDRPLADWLQKHNPTeDEYE 185

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  896 RAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTGN 975
Cdd:cd00895    186 KAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGNIKRDRAPFVFTSDMAYVINGGDKPS 265

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  976 TeKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYLKDSLALGKSEEEALKQFKQKFDEALrESWTT 1055
Cdd:cd00895    266 S-RFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQDTEADATTYFTRLIESSL-GSVAT 343


                   ....*....
gi 1046901447 1056 KVNWMAHTV 1064
Cdd:cd00895    344 KLNFFIHNL 352
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 800-1017 2.99e-76

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: 250.71  E-value: 2.99e-76
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  800 VGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDL-RMLPYGCLATGDRSGLIEVVSTSETIADIQLN--SSNVAATAAF 876
Cdd:pfam00454    2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEygENGVPPTAMV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  877 N-----------------------KDALLNWLKEYN-SGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKK-TG 931
Cdd:pfam00454   82 KilhsalnypklklefesrislppKVGLLQWFVKKSpDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVDKtTG 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  932 QLFHIDFGHILGNFKSKFGIKrERVPFILTYDFIHVIqqgktGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAG 1011
Cdd:pfam00454  162 KLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAM-----GPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVADG 235


                   ....*.
gi 1046901447 1012 LPELTS 1017
Cdd:pfam00454  236 LPDWSI 241
PI3Ka cd00864
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 538-684 1.36e-62

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: 209.38  E-value: 1.36e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  538 LKEILDRDPLSQLCENEMDLIWTLRQDCReNFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLDFNYPDQ 617
Cdd:cd00864      7 LLAILLYPPFSTLTEEEKELLWKFRYYLL-NVPKALPKLLKSVNWNDDEEVSELYQLLKWWAPLSPEDALELLSPKYPDP 85

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1046901447  618 YVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALDNRRIGQFLFWHLRSEVHT 684
Cdd:cd00864     86 VVRQYAVRVLESASDDELLLYLPQLVQALKYEPYLDSYLARFLLERALKSQRLGHQLYWNLKSEIHD 152
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
 801-1056 7.84e-50

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: 178.94  E-value: 7.84e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  801 GVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVstSETIADIQLNSSNVaataafnkda 880
Cdd:cd05167     51 AAIFKVGDDCRQDMLALQLISLFKNIFEEVGLDLYLFPYRVVATGPGCGVIEVI--PNSKSRDQIGRETD---------- 118

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  881 llNWLKEYNS---GDD----LDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHIL-----GNfksk 948
Cdd:cd05167    119 --NGLYEYFLskyGDEstpaFQKARRNFIKSMAGYSLVSYLLQIKDRHNGNIMIDDDGHIIHIDFGFIFeispgGN---- 192

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  949 fgIKRERVPFILTYDFIHVIqqGKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSvKDIQYLKDSL 1028
Cdd:cd05167    193 --LGFESAPFKLTKEMVDLM--GGSMESEPFKWFVELCVRGYLAVRPYAEAIVSLVELMLDSGLPCFRG-QTIKNLRERF 267

                          250       260
                   ....*....|....*....|....*...
gi 1046901447 1029 ALGKSEEEALKQFKQKFDEALrESWTTK 1056
Cdd:cd05167    268 ALEMSEREAANFMIKLIADSY-LKIRTK 294
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
 795-1056 1.09e-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: 174.76  E-value: 1.09e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  795 FGEDAVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIQLNssnvaaTA 874
Cdd:cd00893     23 KGWKLVSLIVKTGDDLKQEQLALQLISQFDQIFKEEGLPLWLRPYEILSLGPDSGIIEMIKNAVSIDSLKKK------LD 96

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  875 AFNKD-ALLNWLKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNFKSKFGIkr 953
Cdd:cd00893     97 SFNKFvSLSDFFDDNFGDEAIQKARDNFLQSLVAYSLVCYFLQIKDRHNGNILLDKEGHIIHIDFGFFLSSHPGFYGF-- 174

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  954 ERVPFILTYDFIHVIqqgKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYLKDSLALGKS 1033
Cdd:cd00893    175 EGAPFKLSSEYIEVL---GGVDSELFKEFRKLFLKGFMALRKHSDKILSLVEMMYSGHGITCFGKKTIQQLKQRFNPELT 251

                          250       260
                   ....*....|....*....|...
gi 1046901447 1034 EEEALKQFKQKFDEALReSWTTK 1056
Cdd:cd00893    252 EGELEVYVLSLINKSLD-NWRTR 273
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
 798-1056 6.72e-47

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: 169.97  E-value: 6.72e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  798 DAVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIQLNSSNVAATAAFn 877
Cdd:cd05168     29 DLRSVIVKSGDDLRQELLAMQLIKQFQRIFEEAGLPLWLRPYEILVTSSDSGLIETIPDTVSIDSLKKRFPNFTSLLDY- 107

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  878 kdallnWLKEY--NSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNFKSKFGIkrER 955
Cdd:cd05168    108 ------FERTFgdPNSERFKEAQRNFVESLAAYSLVCYLLQIKDRHNGNILLDSEGHIIHIDFGFMLSNSPGGLGF--ET 179

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  956 VPFILTYDFIHVIqQGKtgNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAG-LPELTSVKD--IQYLKDSLALGK 1032
Cdd:cd05168    180 APFKLTQEYVEVM-GGL--ESDMFRYFKTLMIQGFLALRKHADRIVLLVEIMQQGSkLPCFFGGGEftIEQLRERFKLNL 256

                          250       260
                   ....*....|....*....|....*..
gi 1046901447 1033 SEEealkQFKQKFDEALRES---WTTK 1056
Cdd:cd05168    257 TEE----ECAQFVDSLIDKSlnnWRTR 279
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
 770-1008 9.33e-45

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: 160.96  E-value: 9.33e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  770 ELYVEKCRYMDSKMKPLWLvysnRAFGEDAV--GVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDR 847
Cdd:cd00142      2 ALDVGILKVIHSKQRPKKI----TLIGADGKtySFLLKRRDDLRKDERSFQFMRLIQSILEKESVNLVLPPYKVIPLSEN 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  848 SGLIEVVSTSETIADiqlnssnvaataafnkdaLLNWLKEYN-SGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIM 926
Cdd:cd00142     78 SGLIEIVKDAQTIED------------------LLKSLWRKSpSSQSWLNRRENFSCSLAGYSVLGYIFGIGDRHPSNIM 139

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  927 VKKTGQLFHIDFGHILGNFKSKfgIKRERVPFILTYDFIHVIqqgktGNTEKFGRFRQCCEDAYLILRRHGNLFITLFAL 1006
Cdd:cd00142    140 IEPSGNIFHIDFGFIFSGRKLA--EGVETVPFRLTPMLENAM-----GTAGVNGPFQISMVKIMEILREHADLIVPILEH 212


                   ..
gi 1046901447 1007 ML 1008
Cdd:cd00142    213 SL 214
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 180-288 1.42e-41

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: 147.86  E-value: 1.42e-41
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447   180 HEPSVLENLEDKLYGGKLVVAVHFENSQDVFSFQVSPNLNPIKINELAIQKRLTIRGKEEEASPcDYVLQVSGRVEYVFG 259
Cdd:smart00144    1 TSPSVPEPLPLKTIANKILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQVDPTSE-DYILKVCGRDEYLLG 79

                            90       100
                    ....*....|....*....|....*....
gi 1046901447   260 DHPLIQFQYIRNCVMNRTLPHFILVECCK 288
Cdd:smart00144   80 DHPLGSFEYIRNCLKNGTEPHLVLMTLSA 108
C2_PI3K_like cd08380
C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes ...
 324-497 4.51e-41

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: 148.28  E-value: 4.51e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  324 SHVWDNNNPFQIVLVKGNKLN--TEETVKVHVRAGLFHGTELLCKTVVSSEISGKNDHIWNEQLEFDINICDLPRMARLC 401
Cdd:cd08380      1 KSLWDINFNLRIKIHGITNINllDSEDLKLYVRVQLYHGGEPLCPPQSTKKVPFSTSVTWNEWLTFDILISDLPREARLC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  402 FAVYAVLdkvktkkstktinpskyqtiRKAGKVHYPVAWVNTMVFDFKGQLRSGDVILHSWSSFPDEleemlNPMGTVQT 481
Cdd:cd08380     81 LSIYAVS--------------------EPGSKKEVPLGWVNVPLFDYKGKLRQGMITLNLWPGKKTD-----PRIACTPC 135

                          170
                   ....*....|....*.
gi 1046901447  482 NPYAENATALHIKFPE 497
Cdd:cd08380    136 NNSNENSTRLLIELPE 151
PI3K_p85B smart00143
PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.
 41-118 3.99e-37

PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.


Pssm-ID: 197539  Cd Length: 78  Bit Score: 133.76  E-value: 3.99e-37
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1046901447    41 YIQLEVPREATISYIKQMLWKQVHNYPMFNLLMDIDSYMFACVNQTAVYEELEDETRRLCDVRPFLPVLKLVTRSCDP 118
Cdd:smart00143    1 LVTLRVLREATLSTIKHELFKQARKMPLGQLLQDESSYIFVSVNQTAEIEEFFDETRRLSDLRLFFPFLKLIEPVGNR 78
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
707-1054 4.23e-34

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 142.61  E-value: 4.23e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  707 KVLSKQVEALNK-----LKTLNSLIKLNAMKLNRAKGKEAMHTCLKQsAYREALSDLQSPLNPCVILSELYVEKCRYMDS 781
Cdd:COG5032   1701 KKFKIDISLLNLsrklyISVLRSIRKRLKRLLELRLKKVSPKLLLFH-AFLEIKLPGQYLLDKPFVLIERFEPEVSVVKS 1779

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  782 -KMKP--LWLVYSNrafGEDaVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGL----DLRMLPYGCLATGDRSGLIEVV 854
Cdd:COG5032   1780 hLQRPrrLTIRGSD---GKL-YSFIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGIIEWV 1855

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  855 STSETIADI------QLN-SSNVAATAAFNKDALLNWLKEY-------------------NSGDDLD--RAIEEFTLSCA 906
Cdd:COG5032   1856 PNSDTLHSIlreyhkRKNiSIDQEKKLAARLDNLKLLLKDEfftkatlksppvlydwfseSFPNPEDwlTARTNFARSLA 1935

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  907 GYCVASYVLGIGDRHSDNIMV-KKTGQLFHIDFGHILGNFKSKFGIKrERVPFILTYDFIHVIqqGKTGnTEkfGRFRQC 985
Cdd:COG5032   1936 VYSVIGYILGLGDRHPGNILIdRSSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAM--GVSG-VE--GSFREL 2009

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  986 CEDAYLILRRHGNLFITLFALMLT------AGLPE--LTSVKDIQYLKDSLALGKSEEEALKQFK---QKFDEALRESWT 1054
Cdd:COG5032   2010 CETAFRALRKNADSLMNVLELFVRdpliewRRLPCfrEIQNNEIVNVLERFRLKLSEKDAEKFVDlliNKSVESLITQAT 2089
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 180-288 5.99e-33

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: 123.17  E-value: 5.99e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  180 HEPSVLENLEdKLYGGKLVVAVHFENSQDVFSFQVSPNLNPIKINELAIQKRLTIRGKEEEASpcDYVLQVSGRVEYVFG 259
Cdd:pfam00794    1 ASTVSPEPLP-KLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVTD--DYVLKVCGRDEYLLG 77

                           90       100
                   ....*....|....*....|....*....
gi 1046901447  260 DHPLIQFQYIRNCVMNRTLPHFILVECCK 288
Cdd:pfam00794   78 DHPLGQFEYIRNCLKSGREPHLTLVEQSS 106
PI3Ka_III cd00870
Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is ...
 538-683 6.66e-32

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


Pssm-ID: 238442  Cd Length: 166  Bit Score: 122.44  E-value: 6.66e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  538 LKEILDRDPLSQLCENEMDLIWTLRQDCReNFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLDFNYPDQ 617
Cdd:cd00870     14 LNKILKYPPTTKLTDEEKDLIWKFRFYLT-NNKKALTKFLKSVNWSDEQEVKQALELMPKWAKIDIEDALELLSPYFTNP 92

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1046901447  618 YVREYAVGCLRQMSDEELSQYLLQLVQVLKYE-------PFLDCALSRFLLERALDNRRIGQFLFWHLRSEVH 683
Cdd:cd00870     93 VVRKYAVSRLKLASDEELLLYLLQLVQALKYEnldlsplPRLDSPLADFLIERALKNPKLANFLYWYLKVELE 165
PI3K_p85B pfam02192
PI3-kinase family, p85-binding domain;
44-117 1.38e-31

PI3-kinase family, p85-binding domain;


Pssm-ID: 460483  Cd Length: 74  Bit Score: 118.00  E-value: 1.38e-31
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1046901447   44 LEVPREATISYIKQMLWKQVHNYPMFNLLMDIDSYMFACVNQTAVYEELEDETRRLCDVRPFLPVLKLVTRSCD 117
Cdd:pfam02192    1 LRVSRNATLSEIKEELWEEAKKYPLYYLLKDPQSYVFTCINQTAEIEELYDETRRLCDVRPFFPILKLVEREGD 74
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
 538-697 4.10e-31

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


Pssm-ID: 238441  Cd Length: 169  Bit Score: 120.25  E-value: 4.10e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  538 LKEILDRDPLSQLCENEMDLIWTLRQDCrENFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLDFNYPDQ 617
Cdd:cd00869      7 LLDLIQKQSTYTLSTEDKDLLWEKRLYC-TNEPNALPLVLASAPSWDWANLMDVYQLLHQWAPLRPLIALELLLPKFPDQ 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  618 YVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALDNRRIGQFLFWHLRSEVHTPAVSIQFGVILEA 697
Cdd:cd00869     86 EVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALDDCYFSSAYQDLGAA 165
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 321-409 1.39e-27

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 107.43  E-value: 1.39e-27
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447   321 RVISHVWDNNNPFQ--IVLVKGNKLNTEETV-KVHVRAGLFHGTELLCKTVVSSEISGKNDHIWNEQLEFDINICDLPRM 397
Cdd:smart00142    1 VKIESLWDCDRNLVitIALIHGIPLNWSRDYsDLYVEIQLYHGGKLLCLPVSTSYKPFFPSVKWNEWLTFPIQISDLPRE 80

                            90
                    ....*....|..
gi 1046901447   398 ARLCFAVYAVLD 409
Cdd:smart00142   81 ARLCITIYAVKN 92
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
 803-1008 5.72e-27

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: 110.05  E-value: 5.72e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  803 IFKNGDDLRQDMLTLQMLRLMD-LLWKEAGLDLRMLP---YGCLATGDRSGLIEVVSTSETIadiqlnssnvaataafnK 878
Cdd:cd05164     33 LVKGDDDLRKDERVMQLFQLLNtLLEKDKETRKRNLTirtYSVVPLSSQSGLIEWVDNTTTL-----------------K 95

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  879 DALLNWLKE-YNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMV-KKTGQLFHIDFGHILGnfKSKFGIKRERV 956
Cdd:cd05164     96 PVLKKWFNEtFPDPTQWYEARSNYTKSTAVMSMVGYIIGLGDRHLENILIdTKTGEVVHIDFGMIFN--KGKTLPVPEIV 173

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1046901447  957 PFILTYDFIHVIqqgktGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALML 1008
Cdd:cd05164    174 PFRLTRNIINGM-----GPTGVEGLFRKSCEQVLRVFRKHKDKLITFLDTFL 220
C2_PI3K_class_I_alpha cd08398
C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 326-483 3.75e-26

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: 105.64  E-value: 3.75e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  326 VWDNNNPFQIVLVKGNKLNTEETVKVHVRAGLFHGTELLCKTVVSSEISGKNDHiWNEQLEFDINICDLPRMARLCFAVY 405
Cdd:cd08398      3 LWKINSNLRIKILCATYVNVNDIDKIYVRTGIYHGGEPLCDNVNTQRVPCSNPR-WNEWLDYDIYIPDLPRSARLCLSIC 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1046901447  406 AVldkvktkkstktinpskyQTIRKAGKVHYPVAWVNTMVFDFKGQLRSGDVILHSWsSFPDELEEMLNPMGTVQTNP 483
Cdd:cd08398     82 SV------------------KGRKGAKEEHCPLAWGNINLFDYTDTLVSGKMALNLW-PVPHGLEDLLNPIGVTGSNP 140
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
 803-1003 2.21e-23

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: 101.46  E-value: 2.21e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  803 IFKNGDDLRQDMLTLQMLRLMDLLWKEAGL----DLRMLPYGCLATGDRSGLIEVVSTSETIADIQLNSSN--------- 869
Cdd:cd05171     33 LVKGGDDLRQDAVMEQVFELVNQLLKRDKEtrkrKLRIRTYKVVPLSPRSGVLEFVENTIPLGEYLVGASSksgaharyr 112

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  870 ------------VAATAAFNKDALLNWLKE----------------YNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRH 921
Cdd:cd05171    113 pkdwtastcrkkMREKAKASAEERLKVFDEicknfkpvfrhfflekFPDPSDWFERRLAYTRSVATSSIVGYILGLGDRH 192

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  922 SDNIMV-KKTGQLFHIDFGHILGnfkskFGiKR----ERVPFILTYDFIHVIqqGKTGnTEkfGRFRQCCEDAYLILRRH 996
Cdd:cd05171    193 LNNILIdQKTGELVHIDLGIAFE-----QG-KLlpipETVPFRLTRDIVDGM--GITG-VE--GVFRRCCEETLRVLREN 261


                   ....*..
gi 1046901447  997 GNLFITL 1003
Cdd:cd05171    262 KEALLTI 268
PIKKc_DNA-PK cd05172
Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, ...
 803-969 1.82e-19

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: 88.79  E-value: 1.82e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  803 IFKNGDDLRQDMLTLQMLRLMDLLWKE----AGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIqlnssnvaataaFNK 878
Cdd:cd05172     33 LVKGGEDLRQDQRIQQLFDVMNNILASdpacRQRRLRIRTYQVIPMTSRLGLIEWVDNTTPLKEI------------LEN 100

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  879 DALLNWLKEYNSGDDLDRAIE-EFTLSCAGYCVASYVLGIGDRHSDNIMV-KKTGQLFHIDFGHILGNFKSKFGIKrERV 956
Cdd:cd05172    101 DLLRRALLSLASSPEAFLALRsNFARSLAAMSICGYILGIGDRHLSNFLVdLSTGRLIGIDFGHAFGSATQFLPIP-ELV 179

                          170
                   ....*....|...
gi 1046901447  957 PFILTYDFIHVIQ 969
Cdd:cd05172    180 PFRLTRQLLNLLQ 192
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 350-471 7.35e-19

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: 83.96  E-value: 7.35e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  350 KVHVRAGLFHGTELLCKTVVSSEISGKNDHI-WNEQLEFDINICDLPRMARLCFAVYAVLDkvktkkstktinpskyqti 428
Cdd:pfam00792    4 DLYVECQLYHGGKPLCLPVSTRYVPFSNSSIkWNEWITFPIQISDLPRSARLCITIWDVSG------------------- 64

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1046901447  429 rkAGKVHYPVAWVNTMVFDFKGQLRSGDVILHSWSSFPDELEE 471
Cdd:pfam00792   65 --PEKSFVPIGWVNTSLFDKKGILRQGKQKLRLWPSKSTPGRS 105
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 779-996 3.08e-18

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: 85.25  E-value: 3.08e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  779 MDSKMKP--LWLVysnrafGEDAVGVIF--KNGDDLRQDMltlqmlRLMD-------LLWKEAGLDLRMLP---YGCLAT 844
Cdd:cd00892     11 MPSLQKPkkITLV------GSDGKKYPFlcKPKDDLRKDA------RMMEfntlinrLLSKDPESRRRNLHirtYAVIPL 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  845 GDRSGLIEVVSTSETIADIqLNSsnvaataaFNKDALLNW-LKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSD 923
Cdd:cd00892     79 NEECGIIEWVPNTVTLRSI-LST--------LYPPVLHEWfLKNFPDPTAWYEARNNYTRSTAVMSMVGYILGLGDRHGE 149

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1046901447  924 NIMV-KKTGQLFHIDFGHILGNFKsKFGIKrERVPFILTYDFIHVIqqGKTGnTEkfGRFRQCCEDAYLILRRH 996
Cdd:cd00892    150 NILFdSTTGDVVHVDFDCLFDKGL-TLEVP-ERVPFRLTQNMVDAM--GVTG-VE--GTFRRTCEVTLRVLREN 216
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 805-1010 6.80e-18

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: 85.23  E-value: 6.80e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  805 KNGDDLRQDMLTLQMLRLMDLLWKE----AGLDLRMLPYGCLATGDRSGLIEVVSTSETIA----------DIQLN---S 867
Cdd:cd05169     35 KGHEDLRLDERVMQLFGLVNTLLKNdsetSRRNLSIQRYSVIPLSPNSGLIGWVPGCDTLHslirdyrekrKIPLNiehR 114

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  868 SNVAATAAFN------KDALLNWLKEYNSGDDLDRAI-------EE-------FTLSCAGYCVASYVLGIGDRHSDNIMV 927
Cdd:cd05169    115 LMLQMAPDYDnltliqKVEVFEYALENTPGDDLRRVLwlkspssEAwlerrtnFTRSLAVMSMVGYILGLGDRHPSNIML 194

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  928 -KKTGQLFHIDFG-------HilgnfKSKFgikRERVPFILTYDFIHVIQQGKTGntekfGRFRQCCEDAYLILRRHGNl 999
Cdd:cd05169    195 dRLTGKVIHIDFGdcfevamH-----REKF---PEKVPFRLTRMLVNAMEVSGVE-----GTFRSTCEDVMRVLRENKD- 260

                          250
                   ....*....|.
gi 1046901447 1000 fiTLFAlMLTA 1010
Cdd:cd05169    261 --SLMA-VLEA 268
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 352-497 2.54e-17

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: 80.48  E-value: 2.54e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  352 HVRAGLFHGTELLCKTVVSSEISGKNDH----IWNEQLEFDINICDLPRMARLCFAVYAVLDkvktkkstktiNPSKYQT 427
Cdd:cd04012     32 YLSCSLYHGGRLLCSPVTTKPVKITKSFfprvVWDEWIEFPIPVCQLPRESRLVLTLYGTTS-----------SPDGGSN 100

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  428 IRKAGKVhyPVAWVNTMVFDFKGQLRSGDVILHSWSSFPDeleEMLNPMGTvqTNPYAENATALHIKFPE 497
Cdd:cd04012    101 KQRMGPE--ELGWVSLPLFDFRGVLRQGSLLLGLWPPSKD---NPLGPAPP--PLFEQPDRVILQIDFPS 163
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
 896-1004 6.57e-14

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: 73.83  E-value: 6.57e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  896 RAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVK-KTGQLFHIDF------GHILgnfkskfgikR--ERVPFILTYDFIH 966
Cdd:cd05170    189 RVTQRFARSLAVMSMIGYIIGLGDRHLDNILVDlSTGEVVHIDYnvcfekGKRL----------RvpEKVPFRLTQNIEH 258

                           90       100       110
                   ....*....|....*....|....*....|....*...
gi 1046901447  967 VIqqgktGNTEKFGRFRQCCEDAYLILRRHGNLFITLF 1004
Cdd:cd05170    259 AL-----GPTGVEGTFRLSCEQVLKILRKGRETLLTLL 291
C2_PI3K_class_I_gamma cd08399
C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 326-493 7.31e-13

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: 68.01  E-value: 7.31e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  326 VWDNNNPFQIVLVKGNKL----NTEETVkvHVRAGLFHGTELLCKTVVSSEiSGKNDHIWNEQLEFDINICDLPRMARLC 401
Cdd:cd08399      5 LWDCDRKFRVKILGIDIPvlprNTDLTV--FVEANIQHGQQVLCQRRTSPK-PFTEEVLWNTWLEFDIKIKDLPKGALLN 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  402 FAVYAVLDKVKTKKStktinpSKYQTIRKAGKVHYPVAWVNTMVFDFKGQLRSGDVILHSWS-SFPDELEEMLNP-MGTV 479
Cdd:cd08399     82 LQIYCGKAPALSSKK------SAESPSSESKGKHQLLYYVNLLLIDHRFLLRTGEYVLHMWQiSGKGEDQGSVNAdKLTS 155

                          170
                   ....*....|....
gi 1046901447  480 QTNPYAENATALHI 493
Cdd:cd08399    156 ATNPDKENSMSISI 169
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
 800-939 5.44e-08

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: 52.83  E-value: 5.44e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  800 VGVIFKNGDDlRQDMLTLQMLRLMDLLWKEAGLDLrmLPYGCLATGDRSG----LIEVVSTSETIADIQLNSSNVAATAA 875
Cdd:cd13968     19 IGVAVKIGDD-VNNEEGEDLESEMDILRRLKGLEL--NIPKVLVTEDVDGpnilLMELVKGGTLIAYTQEEELDEKDVES 95

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1046901447  876 FnkdallnwlkeYNSgddldraieeftlsCAGYCVA--SYVLGIGDRHSDNIMVKKTGQLFHIDFG 939
Cdd:cd13968     96 I-----------MYQ--------------LAECMRLlhSFHLIHRDLNNDNILLSEDGNVKLIDFG 136
C2_PI3K_class_III cd08397
C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 353-455 2.65e-05

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: 45.70  E-value: 2.65e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  353 VRAGLFHGTELLCKTVVSSEISGKNDHIWNEQLEFDINICDLPRMARLCFAVYAVldkvktkkstktinpskYQTIRKag 432
Cdd:cd08397     34 VTCQVFDDGKPLTLPVQTSYKPFKNRRNWNEWLTLPIKYSDLPRNSQLAITIWDV-----------------SGTGKA-- 94

                           90       100
                   ....*....|....*....|...
gi 1046901447  433 kvhYPVAWVNTMVFDFKGQLRSG 455
Cdd:cd08397     95 ---VPFGGTTLSLFNKDGTLRRG 114
PI4Ka cd00871
Phosphoinositide 4-kinase(PI4K), accessory domain (PIK domain); PIK domain is conserved in PI3 ...
 570-684 1.15e-03

Phosphoinositide 4-kinase(PI4K), accessory domain (PIK domain); PIK domain is conserved in PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. PI4K phosphorylates hydroxylgroup at position 4 on the inositol ring of phosphoinositide, the first commited step in the phosphatidylinositol cycle.


Pssm-ID: 238443  Cd Length: 175  Bit Score: 41.19  E-value: 1.15e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  570 PQSLPKLllsIKW-NKLEDVAQLQALLQiWPKLPPREALELLDFNYPDQ-YVREYAVGCLRQMSDEELSQYLLQLVQVLK 647
Cdd:cd00871     40 PEALPFL---VTGkSVDENSPDLKYLLY-WAPVSPVQALSLFTPQYPGHpLVLQYAVRVLESYPVETVFFYIPQIVQALR 115

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1046901447  648 YEPflDCALSRFLLERALDNRRIGQFLFWHLRSEVHT 684
Cdd:cd00871    116 YDK--MGYVEEYILETAKRSQLFAHQIIWNMQTNCYK 150
PIKK_TRRAP cd05163
Pseudokinase domain of TRansformation/tRanscription domain-Associated Protein; TRRAP belongs ...
 877-961 1.29e-03

Pseudokinase domain of TRansformation/tRanscription domain-Associated Protein; TRRAP belongs to the the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. It contains a FATC (FRAP, ATM and TRRAP, C-terminal) domain and has a large molecular weight. Unlike most PIKK proteins, however, it contains an inactive PI3K-like pseudokinase domain, which lacks the conserved residues necessary for ATP binding and catalytic activity. TRRAP also contains many motifs that may be critical for protein-protein interactions. TRRAP is a common component of many histone acetyltransferase (HAT) complexes, and is responsible for the recruitment of these complexes to chromatin during transcription, replication, and DNA repair. TRRAP also exists in non-HAT complexes such as the p400 and MRN complexes, which are implicated in ATP-dependent remodeling and DNA repair, respectively. The TRRAP pseudokinase domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270707  Cd Length: 252  Bit Score: 41.74  E-value: 1.29e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1046901447  877 NKDALLNW-LKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMV-KKTGQLFHIDFGHILGNFKSKFGIKRE 954
Cdd:cd05163    116 PETILSNYfLRTMPSPSDLWLFRKQFTLQLALSSFMTYVLSLGNRTPHRILIsRSTGNVFMTDFLPSINSQGPLLDNNEP 195


                   ....*..
gi 1046901447  955 rVPFILT 961
Cdd:cd05163    196 -VPFRLT 201
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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