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Conserved domains on  [gi|5453894|ref|NP_006210|]
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phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit beta isoform isoform 1 [Homo sapiens]

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: 778.76  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   706 MKVLSKQVEALNKLKTLNSLIKLNAVKLNRAKGKEAMHTCLKQSAYREALSDLQSPLNPCVILSELYVEKCKYMDSKMKP 785
Cdd:cd05173    1 MKVLSKQVEALNKLKTLNSLIKLNAVKLSKAKGKEAMHTCLRQSAYREALSDLQSPLNPSIILSELNVEKCKYMDSKMKP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   786 LWLVYNNKVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIQL 865
Cdd:cd05173   81 LWIVYNNKLFGGDSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVPYGCLATGDRSGLIEVVSSAETIADIQL 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   866 NSSNVAAAAAFNKDALLNWLKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNF 945
Cdd:cd05173  161 NSSNVAAAAAFNKDALLNWLKEYNSGDDLERAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGNF 240

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   946 KSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYLK 1025
Cdd:cd05173  241 KSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQYCEDAYLILRKNGNLFITLFALMLTAGLPELTSVKDIQYLK 320

                        330       340       350       360
                 ....*....|....*....|....*....|....*....|..
gi 5453894  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 3.88e-96

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: 301.92  E-value: 3.88e-96
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   532 KKFLPVLKEILDRDPLSQLCENEMDLIWTLRQDCREIfPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLD 611
Cdd:cd00872    1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRKK-PQALPKLLLSVKWNKRDDVAQMYQLLKRWPKLKPEQALELLD 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   612 FNYPDQYVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALGNRRIGQFLFWHLRSEVHIPAVSVQF 691
Cdd:cd00872   80 CNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVSQRF 159

                        170
                 ....*....|.
gi 5453894   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 2.10e-90

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: 286.52  E-value: 2.10e-90
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   324 SHVWENNNPFQIVLVKGNKLNT-EETVKVHVRAGLFHGTELLCKTIVSSEVSGKNDHIWNEPLEFDINICDLPRMARLCF 402
Cdd:cd08693    1 KSLWDIEEKFSITLHKISNLNAaERTMKVGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   403 AVYAVLDKVKTkkstktINPSKYQTIRKAGKVHYPVAWVNTMVFDFKGQLRTGDIILHSWSSFPDELEEMLNPMGTVQTN 482
Cdd:cd08693   81 AIYEVSKKAKG------KRSRKNQTKKKKKKDDNPIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESN 154

                        170
                 ....*....|....*....
gi 5453894   483 PYTENATALHVKFPENKKQ 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 2.26e-43

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: 152.87  E-value: 2.26e-43
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894      180 HEPSIPENLEDKLYGGKLIVAVHFENCQDVFSFQVSPNMNPIKVNELAIQKRLTIHGKEDEVSPyDYVLQVSGRVEYVFG 259
Cdd:smart00144    1 TSPSVPEPLPLKTIANKILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQVDPTSE-DYILKVCGRDEYLLG 79

                            90       100
                    ....*....|....*....|....*....
gi 5453894      260 DHPLIQFQYIRNCVMNRALPHFILVECCK 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 8.84e-37

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


:

Pssm-ID: 197539  Cd Length: 78  Bit Score: 132.99  E-value: 8.84e-37
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 5453894       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: 778.76  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   706 MKVLSKQVEALNKLKTLNSLIKLNAVKLNRAKGKEAMHTCLKQSAYREALSDLQSPLNPCVILSELYVEKCKYMDSKMKP 785
Cdd:cd05173    1 MKVLSKQVEALNKLKTLNSLIKLNAVKLSKAKGKEAMHTCLRQSAYREALSDLQSPLNPSIILSELNVEKCKYMDSKMKP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   786 LWLVYNNKVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIQL 865
Cdd:cd05173   81 LWIVYNNKLFGGDSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVPYGCLATGDRSGLIEVVSSAETIADIQL 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   866 NSSNVAAAAAFNKDALLNWLKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNF 945
Cdd:cd05173  161 NSSNVAAAAAFNKDALLNWLKEYNSGDDLERAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGNF 240

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   946 KSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYLK 1025
Cdd:cd05173  241 KSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQYCEDAYLILRKNGNLFITLFALMLTAGLPELTSVKDIQYLK 320

                        330       340       350       360
                 ....*....|....*....|....*....|....*....|..
gi 5453894  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 3.88e-96

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: 301.92  E-value: 3.88e-96
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   532 KKFLPVLKEILDRDPLSQLCENEMDLIWTLRQDCREIfPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLD 611
Cdd:cd00872    1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRKK-PQALPKLLLSVKWNKRDDVAQMYQLLKRWPKLKPEQALELLD 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   612 FNYPDQYVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALGNRRIGQFLFWHLRSEVHIPAVSVQF 691
Cdd:cd00872   80 CNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVSQRF 159

                        170
                 ....*....|.
gi 5453894   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 2.10e-90

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: 286.52  E-value: 2.10e-90
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   324 SHVWENNNPFQIVLVKGNKLNT-EETVKVHVRAGLFHGTELLCKTIVSSEVSGKNDHIWNEPLEFDINICDLPRMARLCF 402
Cdd:cd08693    1 KSLWDIEEKFSITLHKISNLNAaERTMKVGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   403 AVYAVLDKVKTkkstktINPSKYQTIRKAGKVHYPVAWVNTMVFDFKGQLRTGDIILHSWSSFPDELEEMLNPMGTVQTN 482
Cdd:cd08693   81 AIYEVSKKAKG------KRSRKNQTKKKKKKDDNPIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESN 154

                        170
                 ....*....|....*....
gi 5453894   483 PYTENATALHVKFPENKKQ 501
Cdd:cd08693  155 PNTESATALHISFPEYKPE 173
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 526-711 2.58e-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: 395488  Cd Length: 185  Bit Score: 265.35  E-value: 2.58e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894     526 VSSRGGKKFLPVLKEILDRDPLSQLCENEMDLIWTLRqDCREIFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPRE 605
Cdd:pfam00613    1 KDLKPNEKERKELEAILAYDPLSKLTAEEKDLIWKFR-YYLMLVPKALTKLLLSVKWSDLSEVAEALSLLLKWAPIDPVD 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894     606 ALELLDFNYPDQYVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALGNRRIGQFLFWHLRSEVHIP 685
Cdd:pfam00613   80 ALELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEIHDE 159

                          170       180
                   ....*....|....*....|....*.
gi 5453894     686 AVSVQFGVILEAYCRGSVGHMKVLSK 711
Cdd:pfam00613  160 EVSPRFGSLLELYLRSCGTSLLGLNK 185
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 538-711 2.01e-80

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: 259.88  E-value: 2.01e-80
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894      538 LKEILDRDPLSQLCENEMDLIWTLRQDCREIFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLDFNYPDQ 617
Cdd:smart00145   11 LEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPKALPKFLLSVKWSDADEVAQALSLLLSWAPLDPEDALELLDPKFPDP 90

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894      618 YVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALGNRRIGQFLFWHLRSEVHIPAVSVQFGVILEA 697
Cdd:smart00145   91 FVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHVSIRFGLLLEA 170

                           170
                    ....*....|....
gi 5453894      698 YCRGSVGHMKVLSK 711
Cdd:smart00145  171 YLRGCGTHLKELLK 184
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 802-1019 2.03e-80

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: 262.23  E-value: 2.03e-80
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894      802 VIFKNGDDLRQDMLTLQMLRLMDLLWKE----AGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIQLNS---------- 867
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKdketRRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894      868 ------------SNVAAAAAFNKDALLNWLKEYNSGDDLD--RAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQL 933
Cdd:smart00146   81 rsqtatrlkkleLFLEATGKFPDPVLYDWFTKKFPDPSEDyfEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894      934 FHIDFGHILGNFKSKFGIKrERVPFILTYDFIHVIqqgktGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLP 1013
Cdd:smart00146  161 FHIDFGFILGNGPKLFGFP-ERVPFRLTPEMVDVM-----GDSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLP 234


                    ....*.
gi 5453894     1014 ELTSVK 1019
Cdd:smart00146  235 DWRSGK 240
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 799-1017 2.33e-74

Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid kinase activity and are protein kinases,.


Pssm-ID: 395364 [Multi-domain]  Cd Length: 241  Bit Score: 245.70  E-value: 2.33e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894     799 SVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDL-RMLPYGCLATGDRSGLIEVVSTSETIADIQLN--SSNVAAAAA 875
Cdd:pfam00454    1 GYGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEygENGVPPTAM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894     876 FN-----------------------KDALLNWLKEYN-SGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKK-T 930
Cdd:pfam00454   81 VKilhsalnypklklefesrislppKVGLLQWFVKKSpDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVDKtT 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894     931 GQLFHIDFGHILGNFKSKFGIKrERVPFILTYDFIHVIqqgktGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTA 1010
Cdd:pfam00454  161 GKLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAM-----GPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVAD 234


                   ....*..
gi 5453894    1011 GLPELTS 1017
Cdd:pfam00454  235 GLPDWSI 241
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 180-288 2.26e-43

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: 152.87  E-value: 2.26e-43
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894      180 HEPSIPENLEDKLYGGKLIVAVHFENCQDVFSFQVSPNMNPIKVNELAIQKRLTIHGKEDEVSPyDYVLQVSGRVEYVFG 259
Cdd:smart00144    1 TSPSVPEPLPLKTIANKILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQVDPTSE-DYILKVCGRDEYLLG 79

                            90       100
                    ....*....|....*....|....*....
gi 5453894      260 DHPLIQFQYIRNCVMNRALPHFILVECCK 288
Cdd:smart00144   80 DHPLGSFEYIRNCLKNGTEPHLVLMTLSA 108
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 180-288 1.07e-37

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: 136.65  E-value: 1.07e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894     180 HEPSIPENLEdKLYGGKLIVAVHFENCQDVFSFQVSPNMNPIKVNELAIQKRLTIHGKEDEVSpyDYVLQVSGRVEYVFG 259
Cdd:pfam00794    1 ASTVSPEPLP-KLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVTD--DYVLKVCGRDEYLLG 77

                           90       100
                   ....*....|....*....|....*....
gi 5453894     260 DHPLIQFQYIRNCVMNRALPHFILVECCK 288
Cdd:pfam00794   78 DHPLGQFEYIRNCLKSGREPHLTLVEQSS 106
PI3K_p85B smart00143
PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.
 41-118 8.84e-37

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


Pssm-ID: 197539  Cd Length: 78  Bit Score: 132.99  E-value: 8.84e-37
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 5453894       41 YIQLEVPREATISYIKQMLWKQVHNYPMFNLLMDIDSYMFACVNQTAVYEELEDETRRLCDVRPFLPVLKLVTRSCDP 118
Cdd:smart00143    1 LVTLRVLREATLSTIKHELFKQARKMPLGQLLQDESSYIFVSVNQTAEIEEFFDETRRLSDLRLFFPFLKLIEPVGNR 78
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
707-1054 1.83e-33

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 140.69  E-value: 1.83e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   707 KVLSKQVEALNK-----LKTLNSLIKLNAVKLNRAKGKEAMHTCLKQsAYREALSDLQSPLNPCVILSELYVEKCKYMDS 781
Cdd:COG5032 1701 KKFKIDISLLNLsrklyISVLRSIRKRLKRLLELRLKKVSPKLLLFH-AFLEIKLPGQYLLDKPFVLIERFEPEVSVVKS 1779

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   782 -KMKPlwlvynNKVFGEDSVG----VIFKNGDDLRQDMLTLQMLRLMDLLWKEAGL----DLRMLPYGCLATGDRSGLIE 852
Cdd:COG5032 1780 hLQRP------RRLTIRGSDGklysFIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGIIE 1853

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   853 VVSTSETIADI------QLN-SSNVAAAAAFNKDALLNWLKEY-------------------NSGDDLD--RAIEEFTLS 904
Cdd:COG5032 1854 WVPNSDTLHSIlreyhkRKNiSIDQEKKLAARLDNLKLLLKDEfftkatlksppvlydwfseSFPNPEDwlTARTNFARS 1933

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   905 CAGYCVASYVLGIGDRHSDNIMV-KKTGQLFHIDFGHILGNFKSKFGIKrERVPFILTYDFIHVIqqgktGNTEKFGRFR 983
Cdd:COG5032 1934 LAVYSVIGYILGLGDRHPGNILIdRSSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAM-----GVSGVEGSFR 2007

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   984 QCCEDAYLILRRHGNLFITLFALMLT------AGLPE--LTSVKDIQYLKDSLALGKSEEEALKQFK---QKFDEALRES 1052
Cdd:COG5032 2008 ELCETAFRALRKNADSLMNVLELFVRdpliewRRLPCfrEIQNNEIVNVLERFRLKLSEKDAEKFVDlliNKSVESLITQ 2087


                 ..
gi 5453894  1053 WT 1054
Cdd:COG5032 2088 AT 2089
PI3K_p85B pfam02192
PI3-kinase family, p85-binding domain;
44-117 1.69e-31

PI3-kinase family, p85-binding domain;


Pssm-ID: 460483  Cd Length: 74  Bit Score: 117.62  E-value: 1.69e-31
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 5453894      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 8.91e-27

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 105.12  E-value: 8.91e-27
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894      321 RIISHVWENNNPFQ--IVLVKGNKLNTEETV-KVHVRAGLFHGTELLCKTIVSSEVSGKNDHIWNEPLEFDINICDLPRM 397
Cdd:smart00142    1 VKIESLWDCDRNLVitIALIHGIPLNWSRDYsDLYVEIQLYHGGKLLCLPVSTSYKPFFPSVKWNEWLTFPIQISDLPRE 80

                            90
                    ....*....|..
gi 5453894      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 1.97e-18

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: 82.80  E-value: 1.97e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894     350 KVHVRAGLFHGTELLCKTIVSSEVSGKNDHI-WNEPLEFDINICDLPRMARLCFAVYAVLDkvktkkstktinpskyqti 428
Cdd:pfam00792    4 DLYVECQLYHGGKPLCLPVSTRYVPFSNSSIkWNEWITFPIQISDLPRSARLCITIWDVSG------------------- 64

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 5453894     429 rkAGKVHYPVAWVNTMVFDFKGQLRTGDIILHSWSSFPDELEE 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: 778.76  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   706 MKVLSKQVEALNKLKTLNSLIKLNAVKLNRAKGKEAMHTCLKQSAYREALSDLQSPLNPCVILSELYVEKCKYMDSKMKP 785
Cdd:cd05173    1 MKVLSKQVEALNKLKTLNSLIKLNAVKLSKAKGKEAMHTCLRQSAYREALSDLQSPLNPSIILSELNVEKCKYMDSKMKP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   786 LWLVYNNKVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIQL 865
Cdd:cd05173   81 LWIVYNNKLFGGDSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVPYGCLATGDRSGLIEVVSSAETIADIQL 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   866 NSSNVAAAAAFNKDALLNWLKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNF 945
Cdd:cd05173  161 NSSNVAAAAAFNKDALLNWLKEYNSGDDLERAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGNF 240

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   946 KSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYLK 1025
Cdd:cd05173  241 KSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQYCEDAYLILRKNGNLFITLFALMLTAGLPELTSVKDIQYLK 320

                        330       340       350       360
                 ....*....|....*....|....*....|....*....|..
gi 5453894  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: 647.00  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   706 MKVLSKQVEALNKLKTLNSLIKLNavKLNRAKGKEAMHTCLKQSAYREALSDLQSPLNPCVILSELYVEKCKYMDSKMKP 785
Cdd:cd05165    1 LKSLSRQVEALNKLKKLSDILKEK--KKSKEKVKKLLKECLKQKFYDEALQNFQSPLNPSHKLGELIIEKCKVMDSKKRP 78

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   786 LWLVYNN---KVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIAD 862
Cdd:cd05165   79 LWLVFENadpLALSGEDIKIIFKNGDDLRQDMLTLQIIRIMDNIWKEEGLDLRMLPYGCLSTGDNVGLIEVVRNAKTIAN 158

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   863 IQLNSSNVAAAAaFNKDALLNWLKEYN-SGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHI 941
Cdd:cd05165  159 IQKKKGKVATLA-FNKDSLHKWLKEKNkTGEKYDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVKENGQLFHIDFGHF 237

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   942 LGNFKSKFGIKRERVPFILTYDFIHVIQQGKTG-NTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKD 1020
Cdd:cd05165  238 LGNFKKKFGIKRERVPFVLTHDFVYVIARGQDNtKSEEFQEFQELCEKAYLILRRHGNLFISLFSMMLSTGIPELTSVKD 317

                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....*.
gi 5453894  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: 642.87  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   705 HMKVLSKQVEALNKLKTLNSLIKLNAVKLNRAKGKEAMHTCLKQSAYREALSDLQSPLNPCVILSELYVEKCKYMDSKMK 784
Cdd:cd05174    3 HMKVLMKQGEALSKMKALNDFVKVSSQKATKPQTKEMMHVCMKQETYMEALSHLQSPLDPSIILEEVCVDQCTFMDSKMK 82

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   785 PLWLVYNNKVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIQ 864
Cdd:cd05174   83 PLWIMYSSEEAGAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTIANIQ 162

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   865 LNSSNVAAAAAFNKDALLNWLKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGN 944
Cdd:cd05174  163 LNKSNMAATAAFNKDALLNWLKSKNPGDALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGN 242

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   945 FKSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYL 1024
Cdd:cd05174  243 FKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCSKDIQYL 322

                        330       340       350       360
                 ....*....|....*....|....*....|....*....|...
gi 5453894  1025 KDSLALGKSEEEALKQFKQKFDEALRESWTTKVNWMAHTVRKD 1067
Cdd:cd05174  323 KDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKD 365
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 706-1050 1.05e-158

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: 472.83  E-value: 1.05e-158
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   706 MKVLSKQVEALNKLKTLNSLIKlnavKLNRAKGKEAMHTCLKQSAYREALsdlQSPLNPCVILSELYVEKCKYMDSKMKP 785
Cdd:cd00891    1 REELLKQVKVLDELKEIAKKIK----EEPSEERKEVLEKLLQKLELPKKF---TLPLDPRMEVKGLIVEKCKVMDSKKLP 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   786 LWLVYNNKVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIQl 865
Cdd:cd00891   74 LWLVFKNADPGGDPIKVIFKAGDDLRQDQLTLQLLRIMDKLWKKEGLDLRMTPYKCIATGDEVGMIEVVPNSETTAAIQ- 152

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   866 nSSNVAAAAAFNKDALLNWLKEYN-SGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGN 944
Cdd:cd00891  153 -KKYGGFGAAFKDTPISNWLKKHNpTEEEYEEAVENFIRSCAGYCVATYVLGIGDRHNDNIMVTKSGHLFHIDFGHFLGN 231

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   945 FKSKFGIKRERVPFILTYDFIHVIqqgKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYL 1024
Cdd:cd00891  232 FKKKFGIKRERAPFVFTPEMAYVM---GGEDSENFQKFEDLCCKAYNILRKHGNLLINLFSLMLSAGIPELQSIEDIEYL 308

                        330       340
                 ....*....|....*....|....*.
gi 5453894  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 1.32e-116

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: 363.53  E-value: 1.32e-116
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   709 LSKQVEALNKLKTLnsliklnAVKLNRAKGKEamhtclKQSAYREALSDLQS---------PLNPCVILSELYVEKCKYM 779
Cdd:cd05166    4 FLKQHVLVQALTSI-------AEKVKSAKDSA------RENALRRELEQLASfllensfrlPLDPALEVTGVDVRSCSYF 70

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   780 DSKMKPLWLVYNNKVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSET 859
Cdd:cd05166   71 NSNALPLKLVFRNADPRAEPISVIFKVGDDLRQDMLTLQLIRIMDKIWLQEGLDLKMITFRCVPTGNKRGMVELVPEAET 150

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   860 IADIQlnsSNVAAAAAFNKDALLNWLKEYNSG-DDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDF 938
Cdd:cd05166  151 LREIQ---TEHGLTGSFKDRPLADWLQKHNPSeLEYEKAVENFIRSCAGYCVATYVLGICDRHNDNIMLKTSGHLFHIDF 227

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   939 GHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTgNTEKFGRF-RQCCEdAYLILRRHGNLFITLFALMLTAGLPELTS 1017
Cdd:cd05166  228 GKFLGDAQMFGNFKRDRVPFVLTSDMAYVINGGDK-PSSRFQLFvDLCCQ-AFNIIRKNSNLLLNLLSLMLSSGIPGVTQ 305

                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....*..
gi 5453894  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 4.82e-110

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: 346.85  E-value: 4.82e-110
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   756 SDLQSPLNPCVILSELYVEKCKYMDSKMKPLWLVY---NNKVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGL 832
Cdd:cd00894   53 ESFRVPYDPGLRAGALVIEKCKVMASKKKPLWLEFkcaDPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESL 132

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   833 DLRMLPYGCLATGDRSGLIEVVSTSETIADIQlnSSNVAAAAAFNKDALLNWLKEYNSGDD-LDRAIEEFTLSCAGYCVA 911
Cdd:cd00894  133 DLCLLPYGCISTGDKIGMIEIVKDATTIAKIQ--QSTVGNTGAFKDEVLNHWLKEKCPIEEkFQAAVERFVYSCAGYCVA 210

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   912 SYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQCCEDAYL 991
Cdd:cd00894  211 TFVLGIGDRHNDNIMITETGNLFHIDFGHILGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSLHFQKFQDVCVKAYL 290

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 5453894   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 7.85e-110

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: 346.27  E-value: 7.85e-110
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   705 HMKVLSKQVEALNKLKTLNSLIKLNAVKLNRAKGKEAMHTCLKQSAYREALSDLQSPLNPCVILSELYVEKCKYMDSKMK 784
Cdd:cd05175    4 YLKHLSRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKR 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   785 PLWLVYNN-KVFGE---DSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETI 860
Cdd:cd05175   84 PLWLNWENpDIMSEllfQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHTI 163

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   861 ADIQLNSSnVAAAAAFNKDALLNWLKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGH 940
Cdd:cd05175  164 MQIQCKGG-LKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGH 242

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   941 ILGNFKSKFGIKRERVPFILTYDFIHVIQQG--KTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSV 1018
Cdd:cd05175  243 FLDHKKKKFGYKRERVPFVLTQDFLIVISKGaqECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSF 322

                        330       340       350       360
                 ....*....|....*....|....*....|....*....|....*...
gi 5453894  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 3.88e-96

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: 301.92  E-value: 3.88e-96
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   532 KKFLPVLKEILDRDPLSQLCENEMDLIWTLRQDCREIfPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLD 611
Cdd:cd00872    1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRKK-PQALPKLLLSVKWNKRDDVAQMYQLLKRWPKLKPEQALELLD 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   612 FNYPDQYVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALGNRRIGQFLFWHLRSEVHIPAVSVQF 691
Cdd:cd00872   80 CNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVSQRF 159

                        170
                 ....*....|.
gi 5453894   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 2.10e-90

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: 286.52  E-value: 2.10e-90
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   324 SHVWENNNPFQIVLVKGNKLNT-EETVKVHVRAGLFHGTELLCKTIVSSEVSGKNDHIWNEPLEFDINICDLPRMARLCF 402
Cdd:cd08693    1 KSLWDIEEKFSITLHKISNLNAaERTMKVGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCF 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   403 AVYAVLDKVKTkkstktINPSKYQTIRKAGKVHYPVAWVNTMVFDFKGQLRTGDIILHSWSSFPDELEEMLNPMGTVQTN 482
Cdd:cd08693   81 AIYEVSKKAKG------KRSRKNQTKKKKKKDDNPIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESN 154

                        170
                 ....*....|....*....
gi 5453894   483 PYTENATALHVKFPENKKQ 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 1.13e-82

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: 272.62  E-value: 1.13e-82
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   714 EALNKLKTLNSLIKLNAVKLNRAKGKeamhtcLKQSAYREALSDLQS---------PLNPCVILSELYVEKCKYMDSKMK 784
Cdd:cd05176    2 EELEKQTRLVQLLGRVAEKVRQASGS------ARQVALQDGMERVQSffqknkcrlPLSPSLVAKELNIKACSFFSSNAV 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   785 PLWL-VYNNKVFGEDsVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIADI 863
Cdd:cd05176   76 PLKVaLVNADPLGEE-INVMFKVGEDLRQDMLALQMIKIMDKIWLQEGLDLRMVIFKCLSTGKDRGMVELVPSSDTLRKI 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   864 QLNSSnvaAAAAFNKDALLNWLKEYN-SGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHIL 942
Cdd:cd05176  155 QVEYG---VTGSFKDKPLAEWLRKYNpSEEEYEKASENFIYSCAGCCVATYVLGICDRHNDNIMLRSTGHMFHIDFGKFL 231

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   943 GNFKSKFGIKRERVPFILTYDFIHVIQQGKTgNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQ 1022
Cdd:cd05176  232 GHAQMFGSFKRDRAPFVLTSDMAYVINGGEK-PTIRFQLFVDLCCQAYNLIRKHTNLFLNLLSLMLSSGLPELTGIQDLK 310

                        330       340       350       360
                 ....*....|....*....|....*....|....*....|..
gi 5453894  1023 YLKDSLALGKSEEEALKQFKQKFDEALrESWTTKVNWMAHTV 1064
Cdd:cd05176  311 YVFDALQPQTTDAEATIFFTRLIESSL-GSVATKFNFFIHNL 351
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 526-711 2.58e-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: 395488  Cd Length: 185  Bit Score: 265.35  E-value: 2.58e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894     526 VSSRGGKKFLPVLKEILDRDPLSQLCENEMDLIWTLRqDCREIFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPRE 605
Cdd:pfam00613    1 KDLKPNEKERKELEAILAYDPLSKLTAEEKDLIWKFR-YYLMLVPKALTKLLLSVKWSDLSEVAEALSLLLKWAPIDPVD 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894     606 ALELLDFNYPDQYVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALGNRRIGQFLFWHLRSEVHIP 685
Cdd:pfam00613   80 ALELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEIHDE 159

                          170       180
                   ....*....|....*....|....*.
gi 5453894     686 AVSVQFGVILEAYCRGSVGHMKVLSK 711
Cdd:pfam00613  160 EVSPRFGSLLELYLRSCGTSLLGLNK 185
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 538-711 2.01e-80

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: 259.88  E-value: 2.01e-80
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894      538 LKEILDRDPLSQLCENEMDLIWTLRQDCREIFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLDFNYPDQ 617
Cdd:smart00145   11 LEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPKALPKFLLSVKWSDADEVAQALSLLLSWAPLDPEDALELLDPKFPDP 90

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894      618 YVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALGNRRIGQFLFWHLRSEVHIPAVSVQFGVILEA 697
Cdd:smart00145   91 FVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHVSIRFGLLLEA 170

                           170
                    ....*....|....
gi 5453894      698 YCRGSVGHMKVLSK 711
Cdd:smart00145  171 YLRGCGTHLKELLK 184
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 802-1019 2.03e-80

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: 262.23  E-value: 2.03e-80
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894      802 VIFKNGDDLRQDMLTLQMLRLMDLLWKE----AGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIQLNS---------- 867
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKdketRRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894      868 ------------SNVAAAAAFNKDALLNWLKEYNSGDDLD--RAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQL 933
Cdd:smart00146   81 rsqtatrlkkleLFLEATGKFPDPVLYDWFTKKFPDPSEDyfEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894      934 FHIDFGHILGNFKSKFGIKrERVPFILTYDFIHVIqqgktGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLP 1013
Cdd:smart00146  161 FHIDFGFILGNGPKLFGFP-ERVPFRLTPEMVDVM-----GDSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLP 234


                    ....*.
gi 5453894     1014 ELTSVK 1019
Cdd:smart00146  235 DWRSGK 240
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 761-1064 2.43e-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: 260.98  E-value: 2.43e-78
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   761 PLNPCVILSELYVEKCKYMDSKMKPLWLVYNNKVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYG 840
Cdd:cd05177   53 PLNPALRVKGIDADACSYFTSNAAPLKISFINANPLAKNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYR 132

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   841 CLATGDRSGLIEVVSTSETIADIQLNSSnvaAAAAFNKDALLNWLKEYN-SGDDLDRAIEEFTLSCAGYCVASYVLGIGD 919
Cdd:cd05177  133 CLSTGKTQGLVQMVPDAVTLAKIHRESG---LIGPLKENTIEKWFHMHNkLKEDYDKAVRNFFHSCAGWCVVTFILGVCD 209

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   920 RHSDNIMVKKTGQLFHIDFGHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTgNTEKFGRFRQCCEDAYLILRRHGNL 999
Cdd:cd05177  210 RHNDNIMLTHSGHMFHIDFGKFLGHAQTFGSIKRDRAPFIFTSEMEYFITEGGK-KPQRFQRFVELCCRAYNIVRKHSQL 288

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 5453894  1000 FITLFALMLTAGLPELTSVKDIQYLKDSLALGKSEEEALKQFKQKFDEALrESWTTKVNWMAHTV 1064
Cdd:cd05177  289 LLNLLEMMLHAGLPELKDIQDLKYVYNNLRPQDTDLEATSYFTKKIKESL-ECFPVKLNNLIHTL 352
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 707-1049 2.07e-77

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: 257.85  E-value: 2.07e-77
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   707 KVLSKQVEALNKLKTLNSLIKlnAVKLNRAKGKEAMHTCLKQSAYREALSD--LQSPLNPCVILSELYVEKCKYMDSKMK 784
Cdd:cd00896    2 EALKRQQEFVDRLRSLMKEVK--NEKGSRDKKIERLRELLSDSELGLLLFFepLPLPLDPSVKVTGIIPEKSTVFKSALM 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   785 PLWLVYNNKVFGEdsVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIq 864
Cdd:cd00896   80 PLKLTFKTLDGGE--YKVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVPNSKALADI- 156

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   865 LNssnvaaaaafNKDALLNWLKEYNsGDDLDR------AIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDF 938
Cdd:cd00896  157 LK----------KYGSILNFLRKHN-PDESGPygikpeVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHIDF 225

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   939 GHILGN----FKSKFGIKRERVPFIltydfihviqqGKTgNTEKFGRFRQ-CCEdAYLILRRHGNLFITLFALMLTAGLP 1013
Cdd:cd00896  226 GYILGRdpkpFPPPMKLCKEMVEAM-----------GGA-NSEGYKEFKKyCCT-AYNILRKHANLILNLFSLMVDANIP 292

                        330       340       350
                 ....*....|....*....|....*....|....*...
gi 5453894  1014 ELTSVKD--IQYLKDSLALGKSEEEALKQFKQKFDEAL 1049
Cdd:cd00896  293 DIALEPDkaVLKVQEKFRLDLSDEEAEQYFQNLIDESV 330
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 747-1064 3.89e-75

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: 252.23  E-value: 3.89e-75
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   747 KQSAYREALSDLQS----------PLNPCVILSELYVEKCKYMDSKMKPLWLVYNNKVFGEDSVGVIFKNGDDLRQDMLT 816
Cdd:cd00895   29 RQGILREGLEEVKQffsingscrlPLSPSLLVKGIVPRDCSYFNSNAVPLKLSFQNVDPLGENIRVIFKCGDDLRQDMLT 108

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   817 LQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIQLNSSnvaAAAAFNKDALLNWLKEYNSG-DDLD 895
Cdd:cd00895  109 LQMIRIMNKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEHG---VTGSFKDRPLADWLQKHNPTeDEYE 185

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   896 RAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTGN 975
Cdd:cd00895  186 KAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGNIKRDRAPFVFTSDMAYVINGGDKPS 265

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   976 TeKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYLKDSLALGKSEEEALKQFKQKFDEALrESWTT 1055
Cdd:cd00895  266 S-RFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQDTEADATTYFTRLIESSL-GSVAT 343


                 ....*....
gi 5453894  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 ...
 799-1017 2.33e-74

Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid kinase activity and are protein kinases,.


Pssm-ID: 395364 [Multi-domain]  Cd Length: 241  Bit Score: 245.70  E-value: 2.33e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894     799 SVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDL-RMLPYGCLATGDRSGLIEVVSTSETIADIQLN--SSNVAAAAA 875
Cdd:pfam00454    1 GYGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEygENGVPPTAM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894     876 FN-----------------------KDALLNWLKEYN-SGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKK-T 930
Cdd:pfam00454   81 VKilhsalnypklklefesrislppKVGLLQWFVKKSpDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVDKtT 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894     931 GQLFHIDFGHILGNFKSKFGIKrERVPFILTYDFIHVIqqgktGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTA 1010
Cdd:pfam00454  161 GKLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAM-----GPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVAD 234


                   ....*..
gi 5453894    1011 GLPELTS 1017
Cdd:pfam00454  235 GLPDWSI 241
PI3Ka cd00864
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 538-683 8.95e-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: 207.07  E-value: 8.95e-62
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   538 LKEILDRDPLSQLCENEMDLIWTLRQDCREiFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLDFNYPDQ 617
Cdd:cd00864    7 LLAILLYPPFSTLTEEEKELLWKFRYYLLN-VPKALPKLLKSVNWNDDEEVSELYQLLKWWAPLSPEDALELLSPKYPDP 85

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 5453894   618 YVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALGNRRIGQFLFWHLRSEVH 683
Cdd:cd00864   86 VVRQYAVRVLESASDDELLLYLPQLVQALKYEPYLDSYLARFLLERALKSQRLGHQLYWNLKSEIH 151
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
 767-1056 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 5453894   767 ILSELYVEKCKYMDSKMkplwLVYNNKVFGEDSVGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGD 846
Cdd:cd05167   21 FLVTFKVKDCGVDELEH----EGTESEATKEVWQAAIFKVGDDCRQDMLALQLISLFKNIFEEVGLDLYLFPYRVVATGP 96

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   847 RSGLIEVVstSETIADIQLNSSNVaaaaafnkdallNWLKEYNS---GDD----LDRAIEEFTLSCAGYCVASYVLGIGD 919
Cdd:cd05167   97 GCGVIEVI--PNSKSRDQIGRETD------------NGLYEYFLskyGDEstpaFQKARRNFIKSMAGYSLVSYLLQIKD 162

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   920 RHSDNIMVKKTGQLFHIDFGHIL-----GNfkskfgIKRERVPFILTYDFIHVIqqGKTGNTEKFGRFRQCCEDAYLILR 994
Cdd:cd05167  163 RHNGNIMIDDDGHIIHIDFGFIFeispgGN------LGFESAPFKLTKEMVDLM--GGSMESEPFKWFVELCVRGYLAVR 234

                        250       260       270       280       290       300
                 ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 5453894   995 RHGNLFITLFALMLTAGLPELTSvKDIQYLKDSLALGKSEEEALKQFKQKFDEALrESWTTK 1056
Cdd:cd05167  235 PYAEAIVSLVELMLDSGLPCFRG-QTIKNLRERFALEMSEREAANFMIKLIADSY-LKIRTK 294
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
 800-1056 3.15e-48

Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 4-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) to generate PtdIns(4)P, the major precursor in the synthesis of other phosphoinositides including PtdIns(4,5)P2, PtdIns(3,4)P2, and PtdIns(3,4,5)P3. There are two types of PI4Ks, types II and III. Type II PI4Ks lack the characteristic catalytic kinase domain present in PI3Ks and type III PI4Ks, and are excluded from this family. Two isoforms of type III PI4K, alpha and beta, exist in most eukaryotes. The PI4K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270626 [Multi-domain]  Cd Length: 286  Bit Score: 173.60  E-value: 3.15e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   800 VGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIQLNSsnvaaaAAFNKD 879
Cdd:cd00893   28 VSLIVKTGDDLKQEQLALQLISQFDQIFKEEGLPLWLRPYEILSLGPDSGIIEMIKNAVSIDSLKKKL------DSFNKF 101

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   880 -ALLNWLKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNFKSKFGIkrERVPF 958
Cdd:cd00893  102 vSLSDFFDDNFGDEAIQKARDNFLQSLVAYSLVCYFLQIKDRHNGNILLDKEGHIIHIDFGFFLSSHPGFYGF--EGAPF 179

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   959 ILTYDFIHVIqqgKTGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAGLPELTSVKDIQYLKDSLALGKSEEEAL 1038
Cdd:cd00893  180 KLSSEYIEVL---GGVDSELFKEFRKLFLKGFMALRKHSDKILSLVEMMYSGHGITCFGKKTIQQLKQRFNPELTEGELE 256

                        250
                 ....*....|....*...
gi 5453894  1039 KQFKQKFDEALReSWTTK 1056
Cdd:cd00893  257 VYVLSLINKSLD-NWRTR 273
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
 800-1056 1.54e-46

Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 4-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) to generate PtdIns(4)P, the major precursor in the synthesis of other phosphoinositides including PtdIns(4,5)P2, PtdIns(3,4)P2, and PtdIns(3,4,5)P3. Two isoforms of type III PI4K, alpha and beta, exist in most eukaryotes. PI4KIIIbeta (also called Pik1p in yeast) is a 110 kDa protein that is localized to the Golgi and the nucleus. It is required for maintaining the structural integrity of the Golgi complex (GC), and is a key regulator of protein transport from the GC to the plasma membrane. PI4KIIIbeta also functions in the genesis, transport, and exocytosis of synaptic vesicles. The Drosophila PI4KIIIbeta is essential for cytokinesis during spermatogenesis. The PI4K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270712 [Multi-domain]  Cd Length: 292  Bit Score: 168.81  E-value: 1.54e-46
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   800 VGVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIQLNSSNVaaaaafnkD 879
Cdd:cd05168   31 RSVIVKSGDDLRQELLAMQLIKQFQRIFEEAGLPLWLRPYEILVTSSDSGLIETIPDTVSIDSLKKRFPNF--------T 102

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   880 ALLN-WLKEY--NSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVKKTGQLFHIDFGHILGNFKSKFGIkrERV 956
Cdd:cd05168  103 SLLDyFERTFgdPNSERFKEAQRNFVESLAAYSLVCYLLQIKDRHNGNILLDSEGHIIHIDFGFMLSNSPGGLGF--ETA 180

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   957 PFILTYDFIHVIqQGKtgNTEKFGRFRQCCEDAYLILRRHGNLFITLFALMLTAG-LPELTSVKD--IQYLKDSLALGKS 1033
Cdd:cd05168  181 PFKLTQEYVEVM-GGL--ESDMFRYFKTLMIQGFLALRKHADRIVLLVEIMQQGSkLPCFFGGGEftIEQLRERFKLNLT 257

                        250       260
                 ....*....|....*....|....*.
gi 5453894  1034 EEealkQFKQKFDEALRES---WTTK 1056
Cdd:cd05168  258 EE----ECAQFVDSLIDKSlnnWRTR 279
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
 770-1008 8.98e-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: 8.98e-45
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   770 ELYVEKCKYMDSKMKPLWLvynnKVFGEDSV--GVIFKNGDDLRQDMLTLQMLRLMDLLWKEAGLDLRMLPYGCLATGDR 847
Cdd:cd00142    2 ALDVGILKVIHSKQRPKKI----TLIGADGKtySFLLKRRDDLRKDERSFQFMRLIQSILEKESVNLVLPPYKVIPLSEN 77

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   848 SGLIEVVSTSETIADiqlnssnvaaaaafnkdaLLNWLKEYN-SGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIM 926
Cdd:cd00142   78 SGLIEIVKDAQTIED------------------LLKSLWRKSpSSQSWLNRRENFSCSLAGYSVLGYIFGIGDRHPSNIM 139

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   927 VKKTGQLFHIDFGHILGNFKSKfgIKRERVPFILTYDFIHVIqqgktGNTEKFGRFRQCCEDAYLILRRHGNLFITLFAL 1006
Cdd:cd00142  140 IEPSGNIFHIDFGFIFSGRKLA--EGVETVPFRLTPMLENAM-----GTAGVNGPFQISMVKIMEILREHADLIVPILEH 212


                 ..
gi 5453894  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 2.26e-43

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: 152.87  E-value: 2.26e-43
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894      180 HEPSIPENLEDKLYGGKLIVAVHFENCQDVFSFQVSPNMNPIKVNELAIQKRLTIHGKEDEVSPyDYVLQVSGRVEYVFG 259
Cdd:smart00144    1 TSPSVPEPLPLKTIANKILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQVDPTSE-DYILKVCGRDEYLLG 79

                            90       100
                    ....*....|....*....|....*....
gi 5453894      260 DHPLIQFQYIRNCVMNRALPHFILVECCK 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 9.09e-39

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: 141.73  E-value: 9.09e-39
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   324 SHVWENNNPFQIVLVKGNKLN--TEETVKVHVRAGLFHGTELLCKTIVSSEVSGKNDHIWNEPLEFDINICDLPRMARLC 401
Cdd:cd08380    1 KSLWDINFNLRIKIHGITNINllDSEDLKLYVRVQLYHGGEPLCPPQSTKKVPFSTSVTWNEWLTFDILISDLPREARLC 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   402 FAVYAVLdkvktkkstktinpskyqtiRKAGKVHYPVAWVNTMVFDFKGQLRTGDIILHSWSSFPDEleemlNPMGTVQT 481
Cdd:cd08380   81 LSIYAVS--------------------EPGSKKEVPLGWVNVPLFDYKGKLRQGMITLNLWPGKKTD-----PRIACTPC 135

                        170
                 ....*....|....*.
gi 5453894   482 NPYTENATALHVKFPE 497
Cdd:cd08380  136 NNSNENSTRLLIELPE 151
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 180-288 1.07e-37

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: 136.65  E-value: 1.07e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894     180 HEPSIPENLEdKLYGGKLIVAVHFENCQDVFSFQVSPNMNPIKVNELAIQKRLTIHGKEDEVSpyDYVLQVSGRVEYVFG 259
Cdd:pfam00794    1 ASTVSPEPLP-KLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVTD--DYVLKVCGRDEYLLG 77

                           90       100
                   ....*....|....*....|....*....
gi 5453894     260 DHPLIQFQYIRNCVMNRALPHFILVECCK 288
Cdd:pfam00794   78 DHPLGQFEYIRNCLKSGREPHLTLVEQSS 106
PI3K_p85B smart00143
PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.
 41-118 8.84e-37

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


Pssm-ID: 197539  Cd Length: 78  Bit Score: 132.99  E-value: 8.84e-37
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 5453894       41 YIQLEVPREATISYIKQMLWKQVHNYPMFNLLMDIDSYMFACVNQTAVYEELEDETRRLCDVRPFLPVLKLVTRSCDP 118
Cdd:smart00143    1 LVTLRVLREATLSTIKHELFKQARKMPLGQLLQDESSYIFVSVNQTAEIEEFFDETRRLSDLRLFFPFLKLIEPVGNR 78
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
707-1054 1.83e-33

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 140.69  E-value: 1.83e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   707 KVLSKQVEALNK-----LKTLNSLIKLNAVKLNRAKGKEAMHTCLKQsAYREALSDLQSPLNPCVILSELYVEKCKYMDS 781
Cdd:COG5032 1701 KKFKIDISLLNLsrklyISVLRSIRKRLKRLLELRLKKVSPKLLLFH-AFLEIKLPGQYLLDKPFVLIERFEPEVSVVKS 1779

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   782 -KMKPlwlvynNKVFGEDSVG----VIFKNGDDLRQDMLTLQMLRLMDLLWKEAGL----DLRMLPYGCLATGDRSGLIE 852
Cdd:COG5032 1780 hLQRP------RRLTIRGSDGklysFIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGIIE 1853

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   853 VVSTSETIADI------QLN-SSNVAAAAAFNKDALLNWLKEY-------------------NSGDDLD--RAIEEFTLS 904
Cdd:COG5032 1854 WVPNSDTLHSIlreyhkRKNiSIDQEKKLAARLDNLKLLLKDEfftkatlksppvlydwfseSFPNPEDwlTARTNFARS 1933

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   905 CAGYCVASYVLGIGDRHSDNIMV-KKTGQLFHIDFGHILGNFKSKFGIKrERVPFILTYDFIHVIqqgktGNTEKFGRFR 983
Cdd:COG5032 1934 LAVYSVIGYILGLGDRHPGNILIdRSSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAM-----GVSGVEGSFR 2007

                        330       340       350       360       370       380       390       400
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   984 QCCEDAYLILRRHGNLFITLFALMLT------AGLPE--LTSVKDIQYLKDSLALGKSEEEALKQFK---QKFDEALRES 1052
Cdd:COG5032 2008 ELCETAFRALRKNADSLMNVLELFVRdpliewRRLPCfrEIQNNEIVNVLERFRLKLSEKDAEKFVDlliNKSVESLITQ 2087


                 ..
gi 5453894  1053 WT 1054
Cdd:COG5032 2088 AT 2089
PI3K_p85B pfam02192
PI3-kinase family, p85-binding domain;
44-117 1.69e-31

PI3-kinase family, p85-binding domain;


Pssm-ID: 460483  Cd Length: 74  Bit Score: 117.62  E-value: 1.69e-31
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 5453894      44 LEVPREATISYIKQMLWKQVHNYPMFNLLMDIDSYMFACVNQTAVYEELEDETRRLCDVRPFLPVLKLVTRSCD 117
Cdd:pfam02192    1 LRVSRNATLSEIKEELWEEAKKYPLYYLLKDPQSYVFTCINQTAEIEELYDETRRLCDVRPFFPILKLVEREGD 74
PI3Ka_III cd00870
Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is ...
 538-683 2.46e-30

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


Pssm-ID: 238442  Cd Length: 166  Bit Score: 117.82  E-value: 2.46e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   538 LKEILDRDPLSQLCENEMDLIWTLRQDCREiFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLDFNYPDQ 617
Cdd:cd00870   14 LNKILKYPPTTKLTDEEKDLIWKFRFYLTN-NKKALTKFLKSVNWSDEQEVKQALELMPKWAKIDIEDALELLSPYFTNP 92

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 5453894   618 YVREYAVGCLRQMSDEELSQYLLQLVQVLKYE-------PFLDCALSRFLLERALGNRRIGQFLFWHLRSEVH 683
Cdd:cd00870   93 VVRKYAVSRLKLASDEELLLYLLQLVQALKYEnldlsplPRLDSPLADFLIERALKNPKLANFLYWYLKVELE 165
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
 538-697 4.14e-30

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


Pssm-ID: 238441  Cd Length: 169  Bit Score: 117.17  E-value: 4.14e-30
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   538 LKEILDRDPLSQLCENEMDLIWTLRQDCREiFPQSLPKLLLSIKWNKLEDVAQLQALLQIWPKLPPREALELLDFNYPDQ 617
Cdd:cd00869    7 LLDLIQKQSTYTLSTEDKDLLWEKRLYCTN-EPNALPLVLASAPSWDWANLMDVYQLLHQWAPLRPLIALELLLPKFPDQ 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   618 YVREYAVGCLRQMSDEELSQYLLQLVQVLKYEPFLDCALSRFLLERALGNRRIGQFLFWHLRSEVHIPAVSVQFGVILEA 697
Cdd:cd00869   86 EVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALDDCYFSSAYQDLGAA 165
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
 803-1008 8.48e-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: 109.67  E-value: 8.48e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   803 IFKNGDDLRQDMLTLQMLRLMD-LLWKEAGLDLRMLP---YGCLATGDRSGLIEVVSTSETIadiqlnssnvaaaaafnK 878
Cdd:cd05164   33 LVKGDDDLRKDERVMQLFQLLNtLLEKDKETRKRNLTirtYSVVPLSSQSGLIEWVDNTTTL-----------------K 95

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   879 DALLNWLKE-YNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMV-KKTGQLFHIDFGHILGnfKSKFGIKRERV 956
Cdd:cd05164   96 PVLKKWFNEtFPDPTQWYEARSNYTKSTAVMSMVGYIIGLGDRHLENILIdTKTGEVVHIDFGMIFN--KGKTLPVPEIV 173

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|..
gi 5453894   957 PFILTYDFIHVIqqgktGNTEKFGRFRQCCEDAYLILRRHGNLFITLFALML 1008
Cdd:cd05164  174 PFRLTRNIINGM-----GPTGVEGLFRKSCEQVLRVFRKHKDKLITFLDTFL 220
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 321-409 8.91e-27

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 105.12  E-value: 8.91e-27
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894      321 RIISHVWENNNPFQ--IVLVKGNKLNTEETV-KVHVRAGLFHGTELLCKTIVSSEVSGKNDHIWNEPLEFDINICDLPRM 397
Cdd:smart00142    1 VKIESLWDCDRNLVitIALIHGIPLNWSRDYsDLYVEIQLYHGGKLLCLPVSTSYKPFFPSVKWNEWLTFPIQISDLPRE 80

                            90
                    ....*....|..
gi 5453894      398 ARLCFAVYAVLD 409
Cdd:smart00142   81 ARLCITIYAVKN 92
C2_PI3K_class_I_alpha cd08398
C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 326-495 1.68e-25

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: 103.72  E-value: 1.68e-25
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   326 VWENNNPFQIVLVKGNKLNTEETVKVHVRAGLFHGTELLCkTIVSSEVSGKNDHIWNEPLEFDINICDLPRMARLCFAVY 405
Cdd:cd08398    3 LWKINSNLRIKILCATYVNVNDIDKIYVRTGIYHGGEPLC-DNVNTQRVPCSNPRWNEWLDYDIYIPDLPRSARLCLSIC 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   406 AVldkvktkkstktinpskyQTIRKAGKVHYPVAWVNTMVFDFKGQLRTGDIILHSWsSFPDELEEMLNPMGTVQTNPyT 485
Cdd:cd08398   82 SV------------------KGRKGAKEEHCPLAWGNINLFDYTDTLVSGKMALNLW-PVPHGLEDLLNPIGVTGSNP-N 141

                        170
                 ....*....|
gi 5453894   486 ENATALHVKF 495
Cdd:cd08398  142 KDTPCLELEF 151
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
 803-1003 9.06e-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: 99.54  E-value: 9.06e-23
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   803 IFKNGDDLRQDMLTLQMLRLMDLLWKEAGL----DLRMLPYGCLATGDRSGLIEVVSTSETIADIQLNSSN--------- 869
Cdd:cd05171   33 LVKGGDDLRQDAVMEQVFELVNQLLKRDKEtrkrKLRIRTYKVVPLSPRSGVLEFVENTIPLGEYLVGASSksgaharyr 112

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   870 ------------VAAAAAFNKDALLNWLKE----------------YNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRH 921
Cdd:cd05171  113 pkdwtastcrkkMREKAKASAEERLKVFDEicknfkpvfrhfflekFPDPSDWFERRLAYTRSVATSSIVGYILGLGDRH 192

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   922 SDNIMV-KKTGQLFHIDFGHILGnfkskFGiKR----ERVPFILTYDFIHVIqqGKTGnTEkfGRFRQCCEDAYLILRRH 996
Cdd:cd05171  193 LNNILIdQKTGELVHIDLGIAFE-----QG-KLlpipETVPFRLTRDIVDGM--GITG-VE--GVFRRCCEETLRVLREN 261


                 ....*..
gi 5453894   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 1.84e-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: 1.84e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   803 IFKNGDDLRQDMLTLQMLRLMDLLWKE----AGLDLRMLPYGCLATGDRSGLIEVVSTSETIADIqlnssnvaaaaaFNK 878
Cdd:cd05172   33 LVKGGEDLRQDQRIQQLFDVMNNILASdpacRQRRLRIRTYQVIPMTSRLGLIEWVDNTTPLKEI------------LEN 100

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   879 DALLNWLKEYNSGDDLDRAIE-EFTLSCAGYCVASYVLGIGDRHSDNIMV-KKTGQLFHIDFGHILGNFKSKFGIKrERV 956
Cdd:cd05172  101 DLLRRALLSLASSPEAFLALRsNFARSLAAMSICGYILGIGDRHLSNFLVdLSTGRLIGIDFGHAFGSATQFLPIP-ELV 179

                        170
                 ....*....|...
gi 5453894   957 PFILTYDFIHVIQ 969
Cdd:cd05172  180 PFRLTRQLLNLLQ 192
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 774-996 7.77e-19

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: 86.79  E-value: 7.77e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   774 EKCKYMDSKMKPLWLVynnkVFGEDSVGVIF--KNGDDLRQDMltlqmlRLMD-------LLWKEAGLDLRMLP---YGC 841
Cdd:cd00892    6 DEVEIMPSLQKPKKIT----LVGSDGKKYPFlcKPKDDLRKDA------RMMEfntlinrLLSKDPESRRRNLHirtYAV 75

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   842 LATGDRSGLIEVVSTSETIADIqlnssnvaaAAAFNKDALLNW-LKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDR 920
Cdd:cd00892   76 IPLNEECGIIEWVPNTVTLRSI---------LSTLYPPVLHEWfLKNFPDPTAWYEARNNYTRSTAVMSMVGYILGLGDR 146

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 5453894   921 HSDNIMV-KKTGQLFHIDFGHILGNFKsKFGIKrERVPFILTYDFIHVIqqGKTGnTEkfGRFRQCCEDAYLILRRH 996
Cdd:cd00892  147 HGENILFdSTTGDVVHVDFDCLFDKGL-TLEVP-ERVPFRLTQNMVDAM--GVTG-VE--GTFRRTCEVTLRVLREN 216
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 767-1010 1.38e-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: 87.15  E-value: 1.38e-18
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   767 ILSELYVekckyMDSKMKPLWLvynnKVFGEDSVGVIF--KNGDDLRQDMLTLQMLRLMDLLWKE----AGLDLRMLPYG 840
Cdd:cd05169    4 FDPTLEV-----ITSKQRPRKL----TIVGSDGKEYKFllKGHEDLRLDERVMQLFGLVNTLLKNdsetSRRNLSIQRYS 74

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   841 CLATGDRSGLIEVVSTSETIA----------DIQLN-SSNVAAAAAFNKDAL--------LNWLKEYNSGDDLDRAI--- 898
Cdd:cd05169   75 VIPLSPNSGLIGWVPGCDTLHslirdyrekrKIPLNiEHRLMLQMAPDYDNLtliqkvevFEYALENTPGDDLRRVLwlk 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   899 ----EE-------FTLSCAGYCVASYVLGIGDRHSDNIMV-KKTGQLFHIDFG-------HilgnfKSKFgikRERVPFI 959
Cdd:cd05169  155 spssEAwlerrtnFTRSLAVMSMVGYILGLGDRHPSNIMLdRLTGKVIHIDFGdcfevamH-----REKF---PEKVPFR 226

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|.
gi 5453894   960 LTYDFIHVIQQGKTGntekfGRFRQCCEDAYLILRRHGNlfiTLFAlMLTA 1010
Cdd:cd05169  227 LTRMLVNAMEVSGVE-----GTFRSTCEDVMRVLRENKD---SLMA-VLEA 268
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 350-471 1.97e-18

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: 82.80  E-value: 1.97e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894     350 KVHVRAGLFHGTELLCKTIVSSEVSGKNDHI-WNEPLEFDINICDLPRMARLCFAVYAVLDkvktkkstktinpskyqti 428
Cdd:pfam00792    4 DLYVECQLYHGGKPLCLPVSTRYVPFSNSSIkWNEWITFPIQISDLPRSARLCITIWDVSG------------------- 64

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 5453894     429 rkAGKVHYPVAWVNTMVFDFKGQLRTGDIILHSWSSFPDELEE 471
Cdd:pfam00792   65 --PEKSFVPIGWVNTSLFDKKGILRQGKQKLRLWPSKSTPGRS 105
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 352-497 6.27e-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: 79.32  E-value: 6.27e-17
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   352 HVRAGLFHGTELLCKTIVSSEVSGKNDH----IWNEPLEFDINICDLPRMARLCFAVYAVLDkvktkkstktiNPSKYQT 427
Cdd:cd04012   32 YLSCSLYHGGRLLCSPVTTKPVKITKSFfprvVWDEWIEFPIPVCQLPRESRLVLTLYGTTS-----------SPDGGSN 100

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   428 IRKAGKVhyPVAWVNTMVFDFKGQLRTGDIILHSWSSFPDeleEMLNPMGTvqTNPYTENATALHVKFPE 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 6.88e-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: 6.88e-14
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   896 RAIEEFTLSCAGYCVASYVLGIGDRHSDNIMVK-KTGQLFHIDF------GHILgnfkskfgikR--ERVPFILTYDFIH 966
Cdd:cd05170  189 RVTQRFARSLAVMSMIGYIIGLGDRHLDNILVDlSTGEVVHIDYnvcfekGKRL----------RvpEKVPFRLTQNIEH 258

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 5453894   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 1.31e-11

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: 64.55  E-value: 1.31e-11
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   326 VWENNNPFQIVLVKGNKL----NTEETVkvHVRAGLFHGTELLCKTIVSSEVSGKnDHIWNEPLEFDINICDLPRMARLC 401
Cdd:cd08399    5 LWDCDRKFRVKILGIDIPvlprNTDLTV--FVEANIQHGQQVLCQRRTSPKPFTE-EVLWNTWLEFDIKIKDLPKGALLN 81

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   402 FAVYAVLDKVKTKKStktinpSKYQTIRKAGKVHYPVAWVNTMVFDFKGQLRTGDIILHSWS-SFPDELEEMLNP-MGTV 479
Cdd:cd08399   82 LQIYCGKAPALSSKK------SAESPSSESKGKHQLLYYVNLLLIDHRFLLRTGEYVLHMWQiSGKGEDQGSVNAdKLTS 155

                        170
                 ....*....|....
gi 5453894   480 QTNPYTENATALHV 493
Cdd:cd08399  156 ATNPDKENSMSISI 169
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
 799-939 6.05e-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: 52.44  E-value: 6.05e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   799 SVGVIFKNGDDlRQDMLTLQMLRLMDLLWKEAGLDLrmLPYGCLATGDRSG----LIEVVSTSETIADIQLNSsnvaaaa 874
Cdd:cd13968   18 TIGVAVKIGDD-VNNEEGEDLESEMDILRRLKGLEL--NIPKVLVTEDVDGpnilLMELVKGGTLIAYTQEEE------- 87

                         90       100       110       120       130       140
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 5453894   875 afnkdallnwLKEynsgddldRAIEEFTLSCAGYCVA--SYVLGIGDRHSDNIMVKKTGQLFHIDFG 939
Cdd:cd13968   88 ----------LDE--------KDVESIMYQLAECMRLlhSFHLIHRDLNNDNILLSEDGNVKLIDFG 136
C2_PI3K_class_III cd08397
C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 353-462 3.18e-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: 45.32  E-value: 3.18e-05
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   353 VRAGLFHGTELLCKTIVSSEVSGKNDHIWNEPLEFDINICDLPRMARLCFAVYAVldkvktkkstktinpskYQTIRKag 432
Cdd:cd08397   34 VTCQVFDDGKPLTLPVQTSYKPFKNRRNWNEWLTLPIKYSDLPRNSQLAITIWDV-----------------SGTGKA-- 94

                         90       100       110
                 ....*....|....*....|....*....|
gi 5453894   433 kvhYPVAWVNTMVFDFKGQLRTGDIILHSW 462
Cdd:cd08397   95 ---VPFGGTTLSLFNKDGTLRRGRQKLRVW 121
PIKK_TRRAP cd05163
Pseudokinase domain of TRansformation/tRanscription domain-Associated Protein; TRRAP belongs ...
 877-961 1.33e-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: 1.33e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   877 NKDALLNW-LKEYNSGDDLDRAIEEFTLSCAGYCVASYVLGIGDRHSDNIMV-KKTGQLFHIDFGHILGNFKSKFGIKRE 954
Cdd:cd05163  116 PETILSNYfLRTMPSPSDLWLFRKQFTLQLALSSFMTYVLSLGNRTPHRILIsRSTGNVFMTDFLPSINSQGPLLDNNEP 195


                 ....*..
gi 5453894   955 rVPFILT 961
Cdd:cd05163  196 -VPFRLT 201
PI4Ka cd00871
Phosphoinositide 4-kinase(PI4K), accessory domain (PIK domain); PIK domain is conserved in PI3 ...
 570-681 1.97e-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: 40.42  E-value: 1.97e-03
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 5453894   570 PQSLPKLllsIKW-NKLEDVAQLQALLQiWPKLPPREALELLDFNYPDQ-YVREYAVGCLRQMSDEELSQYLLQLVQVLK 647
Cdd:cd00871   40 PEALPFL---VTGkSVDENSPDLKYLLY-WAPVSPVQALSLFTPQYPGHpLVLQYAVRVLESYPVETVFFYIPQIVQALR 115

                         90       100       110
                 ....*....|....*....|....*....|....
gi 5453894   648 YEPflDCALSRFLLERALGNRRIGQFLFWHLRSE 681
Cdd:cd00871  116 YDK--MGYVEEYILETAKRSQLFAHQIIWNMQTN 147
 
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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