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Conserved domains on  [gi|1720407819|ref|XP_030109174|]
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phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform isoform X11 [Mus musculus]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
414-781 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: 813.90  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 414 THHMKVLMKQGEALSKLKALNDFVKVSSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVCsVEQCTFMDS 493
Cdd:cd05174     1 THHMKVLMKQGEALSKMKALNDFVKVSSQKATKPQTKEMMHVCMKQETYMEALSHLQSPLDPSIILEEVC-VDQCTFMDS 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 494 KMKPLWIMYSSEEAGsAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTI 573
Cdd:cd05174    80 KMKPLWIMYSSEEAG-AGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTI 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 574 ANIQLNKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGH 653
Cdd:cd05174   159 ANIQLNKSNMAATAAFNKDALLNWLKSKNPGDALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGH 238
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 654 FLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKD 733
Cdd:cd05174   239 FLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCSKD 318
                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*...
gi 1720407819 734 IQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 781
Cdd:cd05174   319 IQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 366
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
242-422 8.79e-87

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: 272.21  E-value: 8.79e-87
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  242 TEEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEHFPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLSALELL 321
Cdd:smart00145   4 DIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPKALPKFLLSVKWSDADEVAQALSLLLSWAPLDPEDALELL 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  322 DFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMHVPSVALR 401
Cdd:smart00145  84 DPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHVSIR 163
                          170       180
                   ....*....|....*....|.
gi 1720407819  402 FGLIMEAYCRGSTHHMKVLMK 422
Cdd:smart00145 164 FGLLLEAYLRGCGTHLKELLK 184
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
79-219 1.55e-80

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: 255.31  E-value: 1.55e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  79 LVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISVCDLPRMARLCFALYAVVEKAKKARSTK----KKSKKADC 154
Cdd:cd08693    29 VGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCFAIYEVSKKAKGKRSRKnqtkKKKKKDDN 108
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720407819 155 PIAWANLMLFDYKDQLKTGERCLYMWPSVPDEKGELLNPAGTVRGNPNTESAAALVIYLPEVAPH 219
Cdd:cd08693   109 PIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESNPNTESATALHISFPEYKPE 173
 
Name Accession Description Interval E-value
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
414-781 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: 813.90  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 414 THHMKVLMKQGEALSKLKALNDFVKVSSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVCsVEQCTFMDS 493
Cdd:cd05174     1 THHMKVLMKQGEALSKMKALNDFVKVSSQKATKPQTKEMMHVCMKQETYMEALSHLQSPLDPSIILEEVC-VDQCTFMDS 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 494 KMKPLWIMYSSEEAGsAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTI 573
Cdd:cd05174    80 KMKPLWIMYSSEEAG-AGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTI 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 574 ANIQLNKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGH 653
Cdd:cd05174   159 ANIQLNKSNMAATAAFNKDALLNWLKSKNPGDALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGH 238
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 654 FLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKD 733
Cdd:cd05174   239 FLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCSKD 318
                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*...
gi 1720407819 734 IQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 781
Cdd:cd05174   319 IQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 366
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
242-422 8.79e-87

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: 272.21  E-value: 8.79e-87
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  242 TEEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEHFPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLSALELL 321
Cdd:smart00145   4 DIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPKALPKFLLSVKWSDADEVAQALSLLLSWAPLDPEDALELL 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  322 DFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMHVPSVALR 401
Cdd:smart00145  84 DPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHVSIR 163
                          170       180
                   ....*....|....*....|.
gi 1720407819  402 FGLIMEAYCRGSTHHMKVLMK 422
Cdd:smart00145 164 FGLLLEAYLRGCGTHLKELLK 184
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
515-732 2.70e-82

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: 262.62  E-value: 2.70e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  515 IIFKNGDDLRQDMLTLQMIQLMDVLWKQE----GLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQLN----------- 579
Cdd:smart00146   1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEyrkqkgkvldl 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  580 -----------KSNMAATAAFNKDALLNWLKSKNPGEALD--RAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQL 646
Cdd:smart00146  81 rsqtatrlkklELFLEATGKFPDPVLYDWFTKKFPDPSEDyfEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  647 FHIDFGHFLGNFKTKFGiNRERVPFILTYDFVHVIqqgktNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLP 726
Cdd:smart00146 161 FHIDFGFILGNGPKLFG-FPERVPFRLTPEMVDVM-----GDSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLP 234

                   ....*.
gi 1720407819  727 ELSCSK 732
Cdd:smart00146 235 DWRSGK 240
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
79-219 1.55e-80

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: 255.31  E-value: 1.55e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  79 LVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISVCDLPRMARLCFALYAVVEKAKKARSTK----KKSKKADC 154
Cdd:cd08693    29 VGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCFAIYEVSKKAKGKRSRKnqtkKKKKKDDN 108
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720407819 155 PIAWANLMLFDYKDQLKTGERCLYMWPSVPDEKGELLNPAGTVRGNPNTESAAALVIYLPEVAPH 219
Cdd:cd08693   109 PIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESNPNTESATALHISFPEYKPE 173
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
243-413 3.53e-79

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: 251.85  E-value: 3.53e-79
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 243 EEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEhFPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLSALELLD 322
Cdd:cd00872     1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRK-KPQALPKLLLSVKWNKRDDVAQMYQLLKRWPKLKPEQALELLD 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 323 FSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMHVPSVALRF 402
Cdd:cd00872    80 CNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVSQRF 159
                         170
                  ....*....|.
gi 1720407819 403 GLIMEAYCRGS 413
Cdd:cd00872   160 GLLLEAYLRGC 170
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
513-729 1.16e-77

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


Pssm-ID: 395364 [Multi-domain]  Cd Length: 241  Bit Score: 250.32  E-value: 1.16e-77
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 513 VGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDL-RMTPYGCLPTGDRTGLIEVVLHSDTIANIQLNK--SNMAATAAF 589
Cdd:pfam00454   2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEYgeNGVPPTAMV 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 590 N-----------------------KDALLNWLKSKNPG-EALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-RESG 644
Cdd:pfam00454  82 KilhsalnypklklefesrislppKVGLLQWFVKKSPDaEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTTG 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 645 QLFHIDFGHFLGNFKTKFGINrERVPFILTYDFVHVIqqgktNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAG 724
Cdd:pfam00454 162 KLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAM-----GPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVADG 235

                  ....*
gi 1720407819 725 LPELS 729
Cdd:pfam00454 236 LPDWS 240
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
237-422 4.03e-64

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: 212.19  E-value: 4.03e-64
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 237 ERGRITEEEQLQLREILERRGSGELYEHEKDLVWKMRHEVqEHFPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLS 316
Cdd:pfam00613   1 KDLKPNEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYL-MLVPKALTKLLLSVKWSDLSEVAEALSLLLKWAPIDPVD 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 317 ALELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMHVP 396
Cdd:pfam00613  80 ALELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEIHDE 159
                         170       180
                  ....*....|....*....|....*.
gi 1720407819 397 SVALRFGLIMEAYCRGSTHHMKVLMK 422
Cdd:pfam00613 160 EVSPRFGSLLELYLRSCGTSLLGLNK 185
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
418-754 1.96e-37

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 151.86  E-value: 1.96e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  418 KVLMKQGE--ALSKLKALNDFVKVSSQKTTKPQTKEMM--HMCMRQETYMEALSH---LQSPLD-PSTLLEEVCSvEQCT 489
Cdd:COG5032   1698 KIRKKFKIdiSLLNLSRKLYISVLRSIRKRLKRLLELRlkKVSPKLLLFHAFLEIklpGQYLLDkPFVLIERFEP-EVSV 1776
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  490 FMDSKMKPLWIMYSseeaGSAGNV-GIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGL----DLRMTPYGCLPTGDRTGLI 564
Cdd:COG5032   1777 VKSHLQRPRRLTIR----GSDGKLySFIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGII 1852
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  565 EVVLHSDTIANI------QLNKS-NMAATAAFNKDALLNWLKSKNPGEALD---------------------RAIEEFTL 616
Cdd:COG5032   1853 EWVPNSDTLHSIlreyhkRKNISiDQEKKLAARLDNLKLLLKDEFFTKATLksppvlydwfsesfpnpedwlTARTNFAR 1932
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  617 SCAGYCVATYVLGIGDRHSDNIMI-RESGQLFHIDFGHFLGNFKTKFGINrERVPFILTYDFVHVIQQgktnnSEKFERF 695
Cdd:COG5032   1933 SLAVYSVIGYILGLGDRHPGNILIdRSSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAMGV-----SGVEGSF 2006
                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720407819  696 RGYCERAYTILRRHGLLFLHLFALMRAAGLPE---LSCSKDIQY-----LKDSLALGKTEEEALKHF 754
Cdd:COG5032   2007 RELCETAFRALRKNADSLMNVLELFVRDPLIEwrrLPCFREIQNneivnVLERFRLKLSEKDAEKFV 2073
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
79-145 1.23e-24

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 98.57  E-value: 1.23e-24
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720407819   79 LVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISVCDLPRMARLCFALYAVVEKAKKARST 145
Cdd:smart00142  34 LYVEIQLYHGGKLLCLPVSTSYKPFFPSVKWNEWLTFPIQISDLPREARLCITIYAVKNPSKGSEFG 100
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
79-186 8.98e-22

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: 91.66  E-value: 8.98e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  79 LVVQAGLFHGNEMLCKTVSSSEVNVCSE-PVWKQRLEFDISVCDLPRMARLCFALYAVvekakkarstkKKSKKADCPIA 157
Cdd:pfam00792   5 LYVECQLYHGGKPLCLPVSTRYVPFSNSsIKWNEWITFPIQISDLPRSARLCITIWDV-----------SGPEKSFVPIG 73
                          90       100
                  ....*....|....*....|....*....
gi 1720407819 158 WANLMLFDYKDQLKTGERCLYMWPSVPDE 186
Cdd:pfam00792  74 WVNTSLFDKKGILRQGKQKLRLWPSKSTP 102
 
Name Accession Description Interval E-value
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
414-781 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: 813.90  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 414 THHMKVLMKQGEALSKLKALNDFVKVSSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVCsVEQCTFMDS 493
Cdd:cd05174     1 THHMKVLMKQGEALSKMKALNDFVKVSSQKATKPQTKEMMHVCMKQETYMEALSHLQSPLDPSIILEEVC-VDQCTFMDS 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 494 KMKPLWIMYSSEEAGsAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTI 573
Cdd:cd05174    80 KMKPLWIMYSSEEAG-AGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTI 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 574 ANIQLNKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGH 653
Cdd:cd05174   159 ANIQLNKSNMAATAAFNKDALLNWLKSKNPGDALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGH 238
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 654 FLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKD 733
Cdd:cd05174   239 FLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCSKD 318
                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*...
gi 1720407819 734 IQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 781
Cdd:cd05174   319 IQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKDN 366
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
417-779 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: 652.78  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 417 MKVLMKQGEALSKLKALNDFVKVssQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVCsVEQCTFMDSKMK 496
Cdd:cd05165     1 LKSLSRQVEALNKLKKLSDILKE--KKKSKEKVKKLLKECLKQKFYDEALQNFQSPLNPSHKLGELI-IEKCKVMDSKKR 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 497 PLWIMYSSEE--AGSAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIA 574
Cdd:cd05165    78 PLWLVFENADplALSGEDIKIIFKNGDDLRQDMLTLQIIRIMDNIWKEEGLDLRMLPYGCLSTGDNVGLIEVVRNAKTIA 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 575 NIQLNKSNMAaTAAFNKDALLNWLKSKNP-GEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGH 653
Cdd:cd05165   158 NIQKKKGKVA-TLAFNKDSLHKWLKEKNKtGEKYDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVKENGQLFHIDFGH 236
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 654 FLGNFKTKFGINRERVPFILTYDFVHVIQQGKTN-NSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSK 732
Cdd:cd05165   237 FLGNFKKKFGIKRERVPFVLTHDFVYVIARGQDNtKSEEFQEFQELCEKAYLILRRHGNLFISLFSMMLSTGIPELTSVK 316
                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*..
gi 1720407819 733 DIQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSK 779
Cdd:cd05165   317 DIEYLRKTLALDKTEEEALKYFRKKFNEALKGSWTTKVNWFFHNVKH 363
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
417-780 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: 620.44  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 417 MKVLMKQGEALSKLKALNDFVKVSSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVcSVEQCTFMDSKMK 496
Cdd:cd05173     1 MKVLSKQVEALNKLKTLNSLIKLNAVKLSKAKGKEAMHTCLRQSAYREALSDLQSPLNPSIILSEL-NVEKCKYMDSKMK 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 497 PLWIMYSSEEAGSaGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANI 576
Cdd:cd05173    80 PLWIVYNNKLFGG-DSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVPYGCLATGDRSGLIEVVSSAETIADI 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 577 QLNKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLG 656
Cdd:cd05173   159 QLNSSNVAAAAAFNKDALLNWLKEYNSGDDLERAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILG 238
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 657 NFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQY 736
Cdd:cd05173   239 NFKSKFGIKRERVPFILTYDFIHVIQQGKTGNTEKFGRFRQYCEDAYLILRKNGNLFITLFALMLTAGLPELTSVKDIQY 318
                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....
gi 1720407819 737 LKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSKD 780
Cdd:cd05173   319 LKDSLALGKSEEEALKQFRQKFDEALRESWTTKVNWMAHTVRKD 362
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
417-763 5.43e-152

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: 446.63  E-value: 5.43e-152
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 417 MKVLMKQGEALSKLKALNDFVK-VSSQKttkpqtkemmhmcmRQETYMEALSHLQS------PLDPSTlleEVCS--VEQ 487
Cdd:cd00891     1 REELLKQVKVLDELKEIAKKIKeEPSEE--------------RKEVLEKLLQKLELpkkftlPLDPRM---EVKGliVEK 63
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 488 CTFMDSKMKPLWIMYSSEEAGsAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVV 567
Cdd:cd00891    64 CKVMDSKKLPLWLVFKNADPG-GDPIKVIFKAGDDLRQDQLTLQLLRIMDKLWKKEGLDLRMTPYKCIATGDEVGMIEVV 142
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 568 LHSDTIANIQlnKSNMAATAAFNKDALLNWLKSKNPGEA-LDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQL 646
Cdd:cd00891   143 PNSETTAAIQ--KKYGGFGAAFKDTPISNWLKKHNPTEEeYEEAVENFIRSCAGYCVATYVLGIGDRHNDNIMVTKSGHL 220
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 647 FHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIqQGKtnNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLP 726
Cdd:cd00891   221 FHIDFGHFLGNFKKKFGIKRERAPFVFTPEMAYVM-GGE--DSENFQKFEDLCCKAYNILRKHGNLLINLFSLMLSAGIP 297
                         330       340       350
                  ....*....|....*....|....*....|....*..
gi 1720407819 727 ELSCSKDIQYLKDSLALGKTEEEALKHFRVKFNEALR 763
Cdd:cd00891   298 ELQSIEDIEYLRDALQLDLSDEEAAEHFRKLIHESLN 334
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
420-777 6.51e-120

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: 365.07  E-value: 6.51e-120
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 420 LMKQGEALSKLKALNDFVKvssqkttkpQTKEmmhmCMRQETYMEALSHLQS---------PLDPSTLLEEVcSVEQCTF 490
Cdd:cd05166     4 FLKQHVLVQALTSIAEKVK---------SAKD----SARENALRRELEQLASfllensfrlPLDPALEVTGV-DVRSCSY 69
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 491 MDSKMKPLWIMYSSEEAGsAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHS 570
Cdd:cd05166    70 FNSNALPLKLVFRNADPR-AEPISVIFKVGDDLRQDMLTLQLIRIMDKIWLQEGLDLKMITFRCVPTGNKRGMVELVPEA 148
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 571 DTIANIQlnkSNMAATAAFNKDALLNWLKSKNPGE-ALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHI 649
Cdd:cd05166   149 ETLREIQ---TEHGLTGSFKDRPLADWLQKHNPSElEYEKAVENFIRSCAGYCVATYVLGICDRHNDNIMLKTSGHLFHI 225
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 650 DFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKtNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELS 729
Cdd:cd05166   226 DFGKFLGDAQMFGNFKRDRVPFVLTSDMAYVINGGD-KPSSRFQLFVDLCCQAFNIIRKNSNLLLNLLSLMLSSGIPGVT 304
                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*...
gi 1720407819 730 cSKDIQYLKDSLALGKTEEEALKHFRVKFNEALReSWKTKVNWLAHNV 777
Cdd:cd05166   305 -QDDLRYVQDALLPELTDAEATAHFTRMIEESLS-SKFTQLNFFIHNL 350
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
416-779 3.60e-111

Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kalpha plays an important role in insulin signaling. It also mediates physiologic heart growth and provides protection from stress. Activating mutations of PI3Kalpha is associated with diverse forms of cancer at high frequency. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270719 [Multi-domain]  Cd Length: 370  Bit Score: 343.19  E-value: 3.60e-111
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 416 HMKVLMKQGEALSKLKALNDFVKVSSQKTTKPQTKEMMHMCMRQETYMEALSHLQSPLDPSTLLEEVcSVEQCTFMDSKM 495
Cdd:cd05175     4 YLKHLSRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNL-RLEECRIMSSAK 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 496 KPLWIMYSSEEAGSA---GNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDT 572
Cdd:cd05175    83 RPLWLNWENPDIMSEllfQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHT 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 573 IANIQLnKSNMAATAAFNKDALLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFG 652
Cdd:cd05175   163 IMQIQC-KGGLKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFG 241
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 653 HFLGNFKTKFGINRERVPFILTYDFVHVIQQG--KTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSC 730
Cdd:cd05175   242 HFLDHKKKKFGYKRERVPFVLTQDFLIVISKGaqECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQS 321
                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*....
gi 1720407819 731 SKDIQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSK 779
Cdd:cd05175   322 FDDIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQ 370
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
467-777 1.98e-108

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: 335.68  E-value: 1.98e-108
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 467 SHLQSPLDPStLLEEVCSVEQCTFMDSKMKPLWIMYS--SEEAGSAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEG 544
Cdd:cd00894    53 ESFRVPYDPG-LRAGALVIEKCKVMASKKKPLWLEFKcaDPTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETES 131
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 545 LDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQlnKSNMAATAAFNKDALLNWLKSKNP-GEALDRAIEEFTLSCAGYCV 623
Cdd:cd00894   132 LDLCLLPYGCISTGDKIGMIEIVKDATTIAKIQ--QSTVGNTGAFKDEVLNHWLKEKCPiEEKFQAAVERFVYSCAGYCV 209
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 624 ATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSEKFERFRGYCERAY 703
Cdd:cd00894   210 ATFVLGIGDRHNDNIMITETGNLFHIDFGHILGNYKSFLGINKERVPFVLTPDFLFVMGTSGKKTSLHFQKFQDVCVKAY 289
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1720407819 704 TILRRHGLLFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNV 777
Cdd:cd00894   290 LALRHHTNLLIILFSMMLMTGMPQLTSKEDIEYIRDALTVGKSEEDAKKHFLDQIEVCRDKGWTVQFNWFLHLV 363
PI3Kc_C2_alpha cd05176
Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
458-779 8.52e-87

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: 278.79  E-value: 8.52e-87
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 458 RQETYMEALSHLQS---------PLDPSTLLEEVcSVEQCTFMDSKMKPLWI-MYSSEEAGSAGNVgiIFKNGDDLRQDM 527
Cdd:cd05176    29 RQVALQDGMERVQSffqknkcrlPLSPSLVAKEL-NIKACSFFSSNAVPLKVaLVNADPLGEEINV--MFKVGEDLRQDM 105
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 528 LTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQLNksnMAATAAFNKDALLNWLKSKNPGE-A 606
Cdd:cd05176   106 LALQMIKIMDKIWLQEGLDLRMVIFKCLSTGKDRGMVELVPSSDTLRKIQVE---YGVTGSFKDKPLAEWLRKYNPSEeE 182
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 607 LDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKT 686
Cdd:cd05176   183 YEKASENFIYSCAGCCVATYVLGICDRHNDNIMLRSTGHMFHIDFGKFLGHAQMFGSFKRDRAPFVLTSDMAYVINGGEK 262
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 687 NNSeKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEALKHFrVKFNEALRESW 766
Cdd:cd05176   263 PTI-RFQLFVDLCCQAYNLIRKHTNLFLNLLSLMLSSGLPELTGIQDLKYVFDALQPQTTDAEATIFF-TRLIESSLGSV 340
                         330
                  ....*....|...
gi 1720407819 767 KTKVNWLAHNVSK 779
Cdd:cd05176   341 ATKFNFFIHNLAQ 353
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
242-422 8.79e-87

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: 272.21  E-value: 8.79e-87
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  242 TEEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEHFPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLSALELL 321
Cdd:smart00145   4 DIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTNNPKALPKFLLSVKWSDADEVAQALSLLLSWAPLDPEDALELL 83
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  322 DFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMHVPSVALR 401
Cdd:smart00145  84 DPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHVSIR 163
                          170       180
                   ....*....|....*....|.
gi 1720407819  402 FGLIMEAYCRGSTHHMKVLMK 422
Cdd:smart00145 164 FGLLLEAYLRGCGTHLKELLK 184
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
515-732 2.70e-82

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: 262.62  E-value: 2.70e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  515 IIFKNGDDLRQDMLTLQMIQLMDVLWKQE----GLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQLN----------- 579
Cdd:smart00146   1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEyrkqkgkvldl 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  580 -----------KSNMAATAAFNKDALLNWLKSKNPGEALD--RAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQL 646
Cdd:smart00146  81 rsqtatrlkklELFLEATGKFPDPVLYDWFTKKFPDPSEDyfEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  647 FHIDFGHFLGNFKTKFGiNRERVPFILTYDFVHVIqqgktNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLP 726
Cdd:smart00146 161 FHIDFGFILGNGPKLFG-FPERVPFRLTPEMVDVM-----GDSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLP 234

                   ....*.
gi 1720407819  727 ELSCSK 732
Cdd:smart00146 235 DWRSGK 240
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
418-762 1.04e-80

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


Pssm-ID: 270628 [Multi-domain]  Cd Length: 346  Bit Score: 262.08  E-value: 1.04e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 418 KVLMKQGEALSKLKALNDFVKVSSQKTTKpQTKEMMHMCMRQETYMEALSH-LQSPLDPSTLLEEVCSvEQCTFMDSKMK 496
Cdd:cd00896     2 EALKRQQEFVDRLRSLMKEVKNEKGSRDK-KIERLRELLSDSELGLLLFFEpLPLPLDPSVKVTGIIP-EKSTVFKSALM 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 497 PLWIMYSSEEAGSagnVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANI 576
Cdd:cd00896    80 PLKLTFKTLDGGE---YKVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVPNSKALADI 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 577 qLNKSNmaataafnkdALLNWLKSKNPGEA-----LDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDF 651
Cdd:cd00896   157 -LKKYG----------SILNFLRKHNPDESgpygiKPEVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHIDF 225
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 652 GHFLGN----FKTKFGINRERVPFIltydfvhviqqGKTnNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPE 727
Cdd:cd00896   226 GYILGRdpkpFPPPMKLCKEMVEAM-----------GGA-NSEGYKEFKKYCCTAYNILRKHANLILNLFSLMVDANIPD 293
                         330       340       350
                  ....*....|....*....|....*....|....*..
gi 1720407819 728 LSCSKD--IQYLKDSLALGKTEEEALKHFRVKFNEAL 762
Cdd:cd00896   294 IALEPDkaVLKVQEKFRLDLSDEEAEQYFQNLIDESV 330
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
418-779 1.33e-80

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: 262.14  E-value: 1.33e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 418 KVLMKQGEALSKLKALNDFVKVSSqkttKPQTKEMMHMCMRQ-ETYMEALSHLQSPLDPSTLLEEVcSVEQCTFMDSKMK 496
Cdd:cd05177     2 KEFSKETKLISILIDAAEKVKTAS----DTRRKEVLKREASRlEDFFQDVVSCCLPLNPALRVKGI-DADACSYFTSNAA 76
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 497 PLWIMYSSEEAgSAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIANI 576
Cdd:cd05177    77 PLKISFINANP-LAKNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYRCLSTGKTQGLVQMVPDAVTLAKI 155
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 577 QlNKSNMAATaaFNKDALLNWLKSKNPGEA-LDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFL 655
Cdd:cd05177   156 H-RESGLIGP--LKENTIEKWFHMHNKLKEdYDKAVRNFFHSCAGWCVVTFILGVCDRHNDNIMLTHSGHMFHIDFGKFL 232
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 656 GNFKTKFGINRERVPFILTYDFVHVIQQGKtNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQ 735
Cdd:cd05177   233 GHAQTFGSIKRDRAPFIFTSEMEYFITEGG-KKPQRFQRFVELCCRAYNIVRKHSQLLLNLLEMMLHAGLPELKDIQDLK 311
                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....
gi 1720407819 736 YLKDSLALGKTEEEALKHFRVKFNEALrESWKTKVNWLAHNVSK 779
Cdd:cd05177   312 YVYNNLRPQDTDLEATSYFTKKIKESL-ECFPVKLNNLIHTLAQ 354
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
79-219 1.55e-80

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: 255.31  E-value: 1.55e-80
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  79 LVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISVCDLPRMARLCFALYAVVEKAKKARSTK----KKSKKADC 154
Cdd:cd08693    29 VGVQAGLFHGGESLCKTVKTSEVSGKNDPVWNETLEFDINVCDLPRMARLCFAIYEVSKKAKGKRSRKnqtkKKKKKDDN 108
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1720407819 155 PIAWANLMLFDYKDQLKTGERCLYMWPSVPDEKGELLNPAGTVRGNPNTESAAALVIYLPEVAPH 219
Cdd:cd08693   109 PIAWVNTMVFDYKGQLKTGDHTLYMWTYAEDQSEDLLNPLGTVESNPNTESATALHISFPEYKPE 173
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
243-413 3.53e-79

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: 251.85  E-value: 3.53e-79
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 243 EEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEhFPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLSALELLD 322
Cdd:cd00872     1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRK-KPQALPKLLLSVKWNKRDDVAQMYQLLKRWPKLKPEQALELLD 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 323 FSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMHVPSVALRF 402
Cdd:cd00872    80 CNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVSQRF 159
                         170
                  ....*....|.
gi 1720407819 403 GLIMEAYCRGS 413
Cdd:cd00872   160 GLLLEAYLRGC 170
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
513-729 1.16e-77

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


Pssm-ID: 395364 [Multi-domain]  Cd Length: 241  Bit Score: 250.32  E-value: 1.16e-77
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 513 VGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDL-RMTPYGCLPTGDRTGLIEVVLHSDTIANIQLNK--SNMAATAAF 589
Cdd:pfam00454   2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEYgeNGVPPTAMV 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 590 N-----------------------KDALLNWLKSKNPG-EALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-RESG 644
Cdd:pfam00454  82 KilhsalnypklklefesrislppKVGLLQWFVKKSPDaEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTTG 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 645 QLFHIDFGHFLGNFKTKFGINrERVPFILTYDFVHVIqqgktNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAG 724
Cdd:pfam00454 162 KLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAM-----GPSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVADG 235

                  ....*
gi 1720407819 725 LPELS 729
Cdd:pfam00454 236 LPDWS 240
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
472-779 2.63e-76

Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II beta isoform, PI3K-C2beta, contributes to the migration and survival of cancer cells. It regulates Rac activity and impacts membrane ruffling, cell motility, and cadherin-mediated cell-cell adhesion. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 119421 [Multi-domain]  Cd Length: 354  Bit Score: 251.07  E-value: 2.63e-76
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 472 PLDPSTLLEEVcSVEQCTFMDSKMKPLWIMYSSEEAgSAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTP 551
Cdd:cd00895    53 PLSPSLLVKGI-VPRDCSYFNSNAVPLKLSFQNVDP-LGENIRVIFKCGDDLRQDMLTLQMIRIMNKIWVQEGLDMRMVI 130
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 552 YGCLPTGDRTGLIEVVLHSDTIANIQLNKsnmAATAAFNKDALLNWLKSKNPGE-ALDRAIEEFTLSCAGYCVATYVLGI 630
Cdd:cd00895   131 FRCFSTGRGRGMVEMIPNAETLRKIQVEH---GVTGSFKDRPLADWLQKHNPTEdEYEKAVENFIYSCAGCCVATYVLGI 207
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 631 GDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSeKFERFRGYCERAYTILRRHG 710
Cdd:cd00895   208 CDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGNIKRDRAPFVFTSDMAYVINGGDKPSS-RFHDFVDLCCQAYNLIRKHT 286
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1720407819 711 LLFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEALKHFrVKFNEALRESWKTKVNWLAHNVSK 779
Cdd:cd00895   287 HLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQDTEADATTYF-TRLIESSLGSVATKLNFFIHNLAQ 354
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
237-422 4.03e-64

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: 212.19  E-value: 4.03e-64
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 237 ERGRITEEEQLQLREILERRGSGELYEHEKDLVWKMRHEVqEHFPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLS 316
Cdd:pfam00613   1 KDLKPNEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYL-MLVPKALTKLLLSVKWSDLSEVAEALSLLLKWAPIDPVD 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 317 ALELLDFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMHVP 396
Cdd:pfam00613  80 ALELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEIHDE 159
                         170       180
                  ....*....|....*....|....*.
gi 1720407819 397 SVALRFGLIMEAYCRGSTHHMKVLMK 422
Cdd:pfam00613 160 EVSPRFGSLLELYLRSCGTSLLGLNK 185
PI3Ka cd00864
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
244-394 4.45e-54

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: 183.57  E-value: 4.45e-54
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 244 EEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEHfPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLSALELLDF 323
Cdd:cd00864     2 WERKPLLAILLYPPFSTLTEEEKELLWKFRYYLLNV-PKALPKLLKSVNWNDDEEVSELYQLLKWWAPLSPEDALELLSP 80
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720407819 324 SFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMH 394
Cdd:cd00864    81 KYPDPVVRQYAVRVLESASDDELLLYLPQLVQALKYEPYLDSYLARFLLERALKSQRLGHQLYWNLKSEIH 151
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
516-769 2.76e-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: 178.56  E-value: 2.76e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 516 IFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSdtianiqlnKS--NMAATAAFNkda 593
Cdd:cd05167    53 IFKVGDDCRQDMLALQLISLFKNIFEEVGLDLYLFPYRVVATGPGCGVIEVIPNS---------KSrdQIGRETDNG--- 120
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 594 LLNWLKSK--NPG-EALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGhFL------GNFKTkfgi 664
Cdd:cd05167   121 LYEYFLSKygDEStPAFQKARRNFIKSMAGYSLVSYLLQIKDRHNGNIMIDDDGHIIHIDFG-FIfeispgGNLGF---- 195
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 665 nrERVPFILTYDFVHVIqqGKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPelsC--SKDIQYLKDSLA 742
Cdd:cd05167   196 --ESAPFKLTKEMVDLM--GGSMESEPFKWFVELCVRGYLAVRPYAEAIVSLVELMLDSGLP---CfrGQTIKNLRERFA 268
                         250       260
                  ....*....|....*....|....*..
gi 1720407819 743 LGKTEEEALKHFRVKFNEALrESWKTK 769
Cdd:cd05167   269 LEMSEREAANFMIKLIADSY-LKIRTK 294
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
512-769 6.61e-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: 171.29  E-value: 6.61e-48
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 512 NVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVLHSDTIAniQLNKSNMAATAAFNk 591
Cdd:cd00893    27 LVSLIVKTGDDLKQEQLALQLISQFDQIFKEEGLPLWLRPYEILSLGPDSGIIEMIKNAVSID--SLKKKLDSFNKFVS- 103
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 592 daLLNWLKSKNPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGInrERVPF 671
Cdd:cd00893   104 --LSDFFDDNFGDEAIQKARDNFLQSLVAYSLVCYFLQIKDRHNGNILLDKEGHIIHIDFGFFLSSHPGFYGF--EGAPF 179
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 672 ILTYDFVHVIqqgKTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAGLPELSCSKDIQYLKDSLALGKTEEEAL 751
Cdd:cd00893   180 KLSSEYIEVL---GGVDSELFKEFRKLFLKGFMALRKHSDKILSLVEMMYSGHGITCFGKKTIQQLKQRFNPELTEGELE 256
                         250
                  ....*....|....*...
gi 1720407819 752 KHFRVKFNEALReSWKTK 769
Cdd:cd00893   257 VYVLSLINKSLD-NWRTR 273
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
513-769 4.81e-45

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: 163.42  E-value: 4.81e-45
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 513 VGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGLIEVVlhSDTIANIQLNKSNMAATaafnkd 592
Cdd:cd05168    31 RSVIVKSGDDLRQELLAMQLIKQFQRIFEEAGLPLWLRPYEILVTSSDSGLIETI--PDTVSIDSLKKRFPNFT------ 102
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 593 ALLNWLKSK---NPGEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKTKFGInrERV 669
Cdd:cd05168   103 SLLDYFERTfgdPNSERFKEAQRNFVESLAAYSLVCYLLQIKDRHNGNILLDSEGHIIHIDFGFMLSNSPGGLGF--ETA 180
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 670 PFILTYDFVHVIqQGKtnNSEKFERFRGYCERAYTILRRHGLLFLHLFALMRAAG-LPELSCSKD--IQYLKDSLALGKT 746
Cdd:cd05168   181 PFKLTQEYVEVM-GGL--ESDMFRYFKTLMIQGFLALRKHADRIVLLVEIMQQGSkLPCFFGGGEftIEQLRERFKLNLT 257
                         250       260
                  ....*....|....*....|...
gi 1720407819 747 EEEALKHFRVKFNEALReSWKTK 769
Cdd:cd05168   258 EEECAQFVDSLIDKSLN-NWRTR 279
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
485-720 1.92e-43

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: 156.34  E-value: 1.92e-43
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 485 VEQCTFMDSKMKPLWImyssEEAGSAGN-VGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLPTGDRTGL 563
Cdd:cd00142     5 VGILKVIHSKQRPKKI----TLIGADGKtYSFLLKRRDDLRKDERSFQFMRLIQSILEKESVNLVLPPYKVIPLSENSGL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 564 IEVVLHSDTIANiqlnksnmaataafnkdaLLNWLKSKNPG-EALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRE 642
Cdd:cd00142    81 IEIVKDAQTIED------------------LLKSLWRKSPSsQSWLNRRENFSCSLAGYSVLGYIFGIGDRHPSNIMIEP 142
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720407819 643 SGQLFHIDFGHFLGNFKTKFGInrERVPFILTYDFVHVIQQGKTNNsekfeRFRGYCERAYTILRRHGLLFLHLFALM 720
Cdd:cd00142   143 SGNIFHIDFGFIFSGRKLAEGV--ETVPFRLTPMLENAMGTAGVNG-----PFQISMVKIMEILREHADLIVPILEHS 213
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
418-754 1.96e-37

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 151.86  E-value: 1.96e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  418 KVLMKQGE--ALSKLKALNDFVKVSSQKTTKPQTKEMM--HMCMRQETYMEALSH---LQSPLD-PSTLLEEVCSvEQCT 489
Cdd:COG5032   1698 KIRKKFKIdiSLLNLSRKLYISVLRSIRKRLKRLLELRlkKVSPKLLLFHAFLEIklpGQYLLDkPFVLIERFEP-EVSV 1776
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  490 FMDSKMKPLWIMYSseeaGSAGNV-GIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGL----DLRMTPYGCLPTGDRTGLI 564
Cdd:COG5032   1777 VKSHLQRPRRLTIR----GSDGKLySFIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGII 1852
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  565 EVVLHSDTIANI------QLNKS-NMAATAAFNKDALLNWLKSKNPGEALD---------------------RAIEEFTL 616
Cdd:COG5032   1853 EWVPNSDTLHSIlreyhkRKNISiDQEKKLAARLDNLKLLLKDEFFTKATLksppvlydwfsesfpnpedwlTARTNFAR 1932
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  617 SCAGYCVATYVLGIGDRHSDNIMI-RESGQLFHIDFGHFLGNFKTKFGINrERVPFILTYDFVHVIQQgktnnSEKFERF 695
Cdd:COG5032   1933 SLAVYSVIGYILGLGDRHPGNILIdRSSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAMGV-----SGVEGSF 2006
                          330       340       350       360       370       380
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720407819  696 RGYCERAYTILRRHGLLFLHLFALMRAAGLPE---LSCSKDIQY-----LKDSLALGKTEEEALKHF 754
Cdd:COG5032   2007 RELCETAFRALRKNADSLMNVLELFVRDPLIEwrrLPCFREIQNneivnVLERFRLKLSEKDAEKFV 2073
C2_PI3K_like cd08380
C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes ...
78-221 1.63e-35

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: 131.71  E-value: 1.63e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  78 WLVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISVCDLPRMARLCFALYAVvekakkarsTKKKSKKaDCPIA 157
Cdd:cd08380    29 KLYVRVQLYHGGEPLCPPQSTKKVPFSTSVTWNEWLTFDILISDLPREARLCLSIYAV---------SEPGSKK-EVPLG 98
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1720407819 158 WANLMLFDYKDQLKTGERCLYMWPSVPDEkgellNPAGTVRGNPNTESAAALVIYLPEVaPHPV 221
Cdd:cd08380    99 WVNVPLFDYKGKLRQGMITLNLWPGKKTD-----PRIACTPCNNSNENSTRLLIELPEF-SKPV 156
C2_PI3K_class_I_alpha cd08398
C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
81-205 2.23e-30

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: 117.20  E-value: 2.23e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  81 VQAGLFHGNEMLCKTVSSSEVNvCSEPVWKQRLEFDISVCDLPRMARLCFALYAVvekakkarSTKKKSKKADCPIAWAN 160
Cdd:cd08398    30 VRTGIYHGGEPLCDNVNTQRVP-CSNPRWNEWLDYDIYIPDLPRSARLCLSICSV--------KGRKGAKEEHCPLAWGN 100
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*
gi 1720407819 161 LMLFDYKDQLKTGERCLYMWPsVPDEKGELLNPAGTVRGNPNTES 205
Cdd:cd08398   101 INLFDYTDTLVSGKMALNLWP-VPHGLEDLLNPIGVTGSNPNKDT 144
PI3Ka_III cd00870
Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is ...
242-394 2.60e-29

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: 114.35  E-value: 2.60e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 242 TEEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEHfPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLSALELL 321
Cdd:cd00870     7 NSKERKELNKILKYPPTTKLTDEEKDLIWKFRFYLTNN-KKALTKFLKSVNWSDEQEVKQALELMPKWAKIDIEDALELL 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 322 DFSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESY-------LDCELTKFLLGRALANRKIGHFLFWHLRSEMH 394
Cdd:cd00870    86 SPYFTNPVVRKYAVSRLKLASDEELLLYLLQLVQALKYENLdlsplprLDSPLADFLIERALKNPKLANFLYWYLKVELE 165
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
243-394 1.49e-26

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: 106.77  E-value: 1.49e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 243 EEEQLQLREILERRGSGELYEHEKDLVWKMRHEVQEHfPEALARLLLVTKWNKHEDVAQMLYLLCSWPELPVLSALELLD 322
Cdd:cd00869     1 IETQEKLLDLIQKQSTYTLSTEDKDLLWEKRLYCTNE-PNALPLVLASAPSWDWANLMDVYQLLHQWAPLRPLIALELLL 79
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1720407819 323 FSFPDCYVGSFAIKSLRKLTDDELFQYLLQLVQVLKYESYLDCELTKFLLGRALANRKIGHFLFWHLRSEMH 394
Cdd:cd00869    80 PKFPDQEVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALD 151
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
79-145 1.23e-24

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 98.57  E-value: 1.23e-24
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1720407819   79 LVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISVCDLPRMARLCFALYAVVEKAKKARST 145
Cdd:smart00142  34 LYVEIQLYHGGKLLCLPVSTSYKPFFPSVKWNEWLTFPIQISDLPREARLCITIYAVKNPSKGSEFG 100
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
516-710 8.23e-23

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: 97.73  E-value: 8.23e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 516 IFKNGDDLRQDMLTLQMIQLMDVLWKQEG----LDLRMTPYGCLPTGDRTGLIEVVLHSDTIANIqlnksnmaataaFNK 591
Cdd:cd05164    33 LVKGDDDLRKDERVMQLFQLLNTLLEKDKetrkRNLTIRTYSVVPLSSQSGLIEWVDNTTTLKPV------------LKK 100
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 592 DAllnWLKSKNPGEALDrAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-RESGQLFHIDFGHFLGNFKTkFGINrERVP 670
Cdd:cd05164   101 WF---NETFPDPTQWYE-ARSNYTKSTAVMSMVGYIIGLGDRHLENILIdTKTGEVVHIDFGMIFNKGKT-LPVP-EIVP 174
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 1720407819 671 FILTYDFVHVIQQGKTNNSekferFRGYCERAYTILRRHG 710
Cdd:cd05164   175 FRLTRNIINGMGPTGVEGL-----FRKSCEQVLRVFRKHK 209
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
79-186 8.98e-22

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: 91.66  E-value: 8.98e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  79 LVVQAGLFHGNEMLCKTVSSSEVNVCSE-PVWKQRLEFDISVCDLPRMARLCFALYAVvekakkarstkKKSKKADCPIA 157
Cdd:pfam00792   5 LYVECQLYHGGKPLCLPVSTRYVPFSNSsIKWNEWITFPIQISDLPRSARLCITIWDV-----------SGPEKSFVPIG 73
                          90       100
                  ....*....|....*....|....*....
gi 1720407819 158 WANLMLFDYKDQLKTGERCLYMWPSVPDE 186
Cdd:pfam00792  74 WVNTSLFDKKGILRQGKQKLRLWPSKSTP 102
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
491-710 1.08e-20

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: 92.93  E-value: 1.08e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 491 MDSKMKP--LWIMysseeaGSAGNVgIIF--KNGDDLRQDMLTLQMIQLMDVLWKQE----GLDLRMTPYGCLPTGDRTG 562
Cdd:cd05169    11 ITSKQRPrkLTIV------GSDGKE-YKFllKGHEDLRLDERVMQLFGLVNTLLKNDsetsRRNLSIQRYSVIPLSPNSG 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 563 LIEVVLHSDTIA----------NIQLN--KSNMAATA-------------AFN-----------KDALlnWLKSKNPGEA 606
Cdd:cd05169    84 LIGWVPGCDTLHslirdyrekrKIPLNieHRLMLQMApdydnltliqkveVFEyalentpgddlRRVL--WLKSPSSEAW 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 607 LDRAIeEFTLSCAGYCVATYVLGIGDRHSDNIMI-RESGQLFHIDFG-------HflgnfKTKFginRERVPFILTYDFV 678
Cdd:cd05169   162 LERRT-NFTRSLAVMSMVGYILGLGDRHPSNIMLdRLTGKVIHIDFGdcfevamH-----REKF---PEKVPFRLTRMLV 232
                         250       260       270
                  ....*....|....*....|....*....|..
gi 1720407819 679 HVIQQGKTNNSekferFRGYCERAYTILRRHG 710
Cdd:cd05169   233 NAMEVSGVEGT-----FRSTCEDVMRVLRENK 259
PIKKc_DNA-PK cd05172
Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, ...
486-682 3.38e-20

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: 90.33  E-value: 3.38e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 486 EQCTFMDSKMKPLWI-MYSSEEAGSAgnvgIIFKNGDDLRQDMLTLQMIQLMDVLWKQE----GLDLRMTPYGCLPTGDR 560
Cdd:cd05172     6 PRVLVLSSKRRPKRItIRGSDEKEYK----FLVKGGEDLRQDQRIQQLFDVMNNILASDpacrQRRLRIRTYQVIPMTSR 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 561 TGLIEVVLHSDTIANIqlnksnmaataaFNKDALLNWLK--SKNPgEALDRAIEEFTLSCAGYCVATYVLGIGDRHSDNI 638
Cdd:cd05172    82 LGLIEWVDNTTPLKEI------------LENDLLRRALLslASSP-EAFLALRSNFARSLAAMSICGYILGIGDRHLSNF 148
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 1720407819 639 MI-RESGQLFHIDFGHFLGNFKTKFGINrERVPFILTYDFVHVIQ 682
Cdd:cd05172   149 LVdLSTGRLIGIDFGHAFGSATQFLPIP-ELVPFRLTRQLLNLLQ 192
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
516-709 4.29e-19

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: 88.37  E-value: 4.29e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 516 IFKNGDDLRQDMLTLQMIQLMDVLWKQEGL----DLRMTPYGCLPTGDRTGLIEVVLHSDTIANIQLNKSN--------- 582
Cdd:cd05171    33 LVKGGDDLRQDAVMEQVFELVNQLLKRDKEtrkrKLRIRTYKVVPLSPRSGVLEFVENTIPLGEYLVGASSksgaharyr 112
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 583 ------------MAATAAFNKDALLN-----------------WLKSKNPGEALDRaIEEFTLSCAGYCVATYVLGIGDR 633
Cdd:cd05171   113 pkdwtastcrkkMREKAKASAEERLKvfdeicknfkpvfrhffLEKFPDPSDWFER-RLAYTRSVATSSIVGYILGLGDR 191
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 634 HSDNIMI-RESGQLFHIDFG-HFlgnfktKFGIN---RERVPFILTYDFVHVIQQGKTNNSekferFRGYCERAYTILRR 708
Cdd:cd05171   192 HLNNILIdQKTGELVHIDLGiAF------EQGKLlpiPETVPFRLTRDIVDGMGITGVEGV-----FRRCCEETLRVLRE 260

                  .
gi 1720407819 709 H 709
Cdd:cd05171   261 N 261
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
83-217 9.17e-19

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: 84.33  E-value: 9.17e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  83 AGLFHGNEMLCKTVSSSEVNVCSE----PVWKQRLEFDISVCDLPRMARLCFALYAVVEKAKKARSTKKKSKKadcPIAW 158
Cdd:cd04012    35 CSLYHGGRLLCSPVTTKPVKITKSffprVVWDEWIEFPIPVCQLPRESRLVLTLYGTTSSPDGGSNKQRMGPE---ELGW 111
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1720407819 159 ANLMLFDYKDQLKTGERCLYMWPSvpdEKGELLNPAGTVrgNPNTESAAALVIYLPEVA 217
Cdd:cd04012   112 VSLPLFDFRGVLRQGSLLLGLWPP---SKDNPLGPAPPP--LFEQPDRVILQIDFPSSA 165
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
491-709 2.16e-16

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: 79.09  E-value: 2.16e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 491 MDSKMKPLWIMYsseeAGSAGN-VGIIFKNGDDLRQDMLTLQMIQLMDVLWKQ----EGLDLRMTPYGCLPTGDRTGLIE 565
Cdd:cd00892    11 MPSLQKPKKITL----VGSDGKkYPFLCKPKDDLRKDARMMEFNTLINRLLSKdpesRRRNLHIRTYAVIPLNEECGIIE 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 566 VVLHSDTIANIqLNKsnmaataaFNKDALLNWLKSK--NPGEALdRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMI-RE 642
Cdd:cd00892    87 WVPNTVTLRSI-LST--------LYPPVLHEWFLKNfpDPTAWY-EARNNYTRSTAVMSMVGYILGLGDRHGENILFdST 156
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1720407819 643 SGQLFHIDFGHFLGNFKTkFGInRERVPFILTYDFVHVIqqGKTnnseKFE-RFRGYCERAYTILRRH 709
Cdd:cd00892   157 TGDVVHVDFDCLFDKGLT-LEV-PERVPFRLTQNMVDAM--GVT----GVEgTFRRTCEVTLRVLREN 216
C2_PI3K_class_I_gamma cd08399
C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
79-221 1.03e-14

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: 73.02  E-value: 1.03e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  79 LVVQAGLFHGNEMLCKTVSSSEvNVCSEPVWKQRLEFDISVCDLPRMARLCFALYAV----VEKAKKARSTKKKSKKADC 154
Cdd:cd08399    32 VFVEANIQHGQQVLCQRRTSPK-PFTEEVLWNTWLEFDIKIKDLPKGALLNLQIYCGkapaLSSKKSAESPSSESKGKHQ 110
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1720407819 155 PIAWANLMLFDYKDQLKTGERCLYMW--PSVPDEKGELLNPAGTVRGNPNTESAAALVIYLPEVApHPV 221
Cdd:cd08399   111 LLYYVNLLLIDHRFLLRTGEYVLHMWqiSGKGEDQGSVNADKLTSATNPDKENSMSISILLDNYC-HPV 178
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
508-717 4.92e-09

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


Pssm-ID: 270714  Cd Length: 304  Bit Score: 58.42  E-value: 4.92e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 508 GSAGNV-GIIFKNGDDLRQDMLTLQMIQLMDVLW----KQEGLDLRMTPYGCLPTGDRTGLIEVV-------------LH 569
Cdd:cd05170    24 GSDGKRyPYLFKGLEDLHLDERIMQFLSIVNAMLasdnEHRRRRYRARHYSVTPLGPRSGLIQWVdgatplfslykrwQQ 103
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 570 SDTIANIQLNKSNMAATAA--------FNK---------------------DAL---LNWLKSKNPGEALDRAI------ 611
Cdd:cd05170   104 RRAAAQAQKNQDSGSTPPPvprpselfYNKlkpalkaagirkstsrrewplEVLrqvLEELVAETPRDLLARELwcssps 183
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 612 --------EEFTLSCAGYCVATYVLGIGDRHSDNIMIR-ESGQLFHIDF------GHFLgnfktkfginR--ERVPFILT 674
Cdd:cd05170   184 saewwrvtQRFARSLAVMSMIGYIIGLGDRHLDNILVDlSTGEVVHIDYnvcfekGKRL----------RvpEKVPFRLT 253
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 1720407819 675 YDFVHVIqqGKTNnsekFE-RFRGYCERAYTILRRHGLLFLHLF 717
Cdd:cd05170   254 QNIEHAL--GPTG----VEgTFRLSCEQVLKILRKGRETLLTLL 291
PI4Ka cd00871
Phosphoinositide 4-kinase(PI4K), accessory domain (PIK domain); PIK domain is conserved in PI3 ...
279-393 2.93e-08

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: 53.90  E-value: 2.93e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 279 HFPEALArlLLVTKWNKHEDVAQMLYLLCsWPELPVLSALELLDFSFP-DCYVGSFAIKSLRKLTDDELFQYLLQLVQVL 357
Cdd:cd00871    38 KIPEALP--FLVTGKSVDENSPDLKYLLY-WAPVSPVQALSLFTPQYPgHPLVLQYAVRVLESYPVETVFFYIPQIVQAL 114
                          90       100       110
                  ....*....|....*....|....*....|....*.
gi 1720407819 358 KYESylDCELTKFLLGRALANRKIGHFLFWHLRSEM 393
Cdd:cd00871   115 RYDK--MGYVEEYILETAKRSQLFAHQIIWNMQTNC 148
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
508-652 8.06e-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: 51.67  E-value: 8.06e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819 508 GSAGNVGIIFKNGDDlRQDMLTLQMIQLMDVLWKQEGLDLrmTPYGCLPTGDRTG----LIEVVlhsdtianiqlnksnm 583
Cdd:cd13968    14 GECTTIGVAVKIGDD-VNNEEGEDLESEMDILRRLKGLEL--NIPKVLVTEDVDGpnilLMELV---------------- 74
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1720407819 584 aataafnKDALLNWLKSKnpGEALDRAIEEFTLSCAGYCVATYV--LGIGDRHSDNIMIRESGQLFHIDFG 652
Cdd:cd13968    75 -------KGGTLIAYTQE--EELDEKDVESIMYQLAECMRLLHSfhLIHRDLNNDNILLSEDGNVKLIDFG 136
C2_PI3K_class_III cd08397
C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
79-186 5.53e-07

C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a C2 domain, a PIK domain, and a kinase catalytic domain. These are the only domains identified in the class III PI3Ks present in this cd. In addition some PI3Ks contain a Ras-binding domain and/or a p85-binding domain. Class II PI3Ks contain both of these as well as a PX domain, and a C-terminal C2 domain containing a nuclear localization signal. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176042  Cd Length: 159  Bit Score: 49.94  E-value: 5.53e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1720407819  79 LVVQAGLFHGNEMLCKTVSSSEVNVCSEPVWKQRLEFDISVCDLPRMARLCFALYAVVEKAKKarstkkkskkadCPIAW 158
Cdd:cd08397    32 LFVTCQVFDDGKPLTLPVQTSYKPFKNRRNWNEWLTLPIKYSDLPRNSQLAITIWDVSGTGKA------------VPFGG 99
                          90       100
                  ....*....|....*....|....*...
gi 1720407819 159 ANLMLFDYKDQLKTGERCLYMWPSVPDE 186
Cdd:cd08397   100 TTLSLFNKDGTLRRGRQKLRVWPDVEAD 127
PIKK_TRRAP cd05163
Pseudokinase domain of TRansformation/tRanscription domain-Associated Protein; TRRAP belongs ...
613-674 2.96e-04

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


Pssm-ID: 270707  Cd Length: 252  Bit Score: 43.28  E-value: 2.96e-04
                          10        20        30        40        50        60
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1720407819 613 EFTLSCAGYCVATYVLGIGDRHSDNIMI-RESGQLFHIDFgHFLGNFKTKFGINRERVPFILT 674
Cdd:cd05163   140 QFTLQLALSSFMTYVLSLGNRTPHRILIsRSTGNVFMTDF-LPSINSQGPLLDNNEPVPFRLT 201
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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