NCBI Home Page NCBI Site Search page NCBI Guide that lists and describes the NCBI resources
Conserved domains on  [gi|809281416|ref|NP_001294949|]
View 

phosphatidylinositol 3-kinase catalytic subunit type 3 isoform 2 [Homo sapiens]

Protein Classification

phosphatidylinositol 3-kinase( domain architecture ID 10170542)

phosphatidylinositol 3-kinase catalyzes 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

CATH:  1.10.510.10
EC:  2.7.1.137
Gene Ontology:  GO:0052742|GO:0016310|GO:0005524|GO:0046854|GO:0035032
PubMed:  16244704|17371248|9255069

Graphical summary

 Zoom to residue level

show extra options »

Show site features     Horizontal zoom: ×

List of domain hits

 Name Accession Description Interval E-value
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 476-820 0e+00

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: 616.47  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 476 RSLLAAQQTFVDRLVHLMKAVQRESGNRKKKNERLQALLGDNEKMNLSDVELIPLPLEPQVKIRGIIPETATLFKSALMP 555
Cdd:cd00896    1 REALKRQQEFVDRLRSLMKEVKNEKGSRDKKIERLRELLSDSELGLLLFFEPLPLPLDPSVKVTGIIPEKSTVFKSALMP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 556 AQLFFKTEDGGKYPVIFKHGDDLRQDQLILQIISLMDKLLRKENLDLKLTPYKVLATSTKHGFMQFI-QSVPVAEVLDTE 634
Cdd:cd00896   81 LKLTFKTLDGGEYKVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVpNSKALADILKKY 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 635 GSIQNFFRKYAPSENGPNGISAEVMDTYVKSCAGYCVITYILGVGDRHLDNLLLTKTGKLFHIDFGYILGRDPKPLPPPM 714
Cdd:cd00896  161 GSILNFLRKHNPDESGPYGIKPEVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHIDFGYILGRDPKPFPPPM 240

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 715 KLNKEMVEGMGGTQSEQYQEFRKQCYTAFLHLRRYSNLILNLFSLMVDANIPDIALEPDKTVKKVQDKFRLDLSDEEAVH 794
Cdd:cd00896  241 KLCKEMVEAMGGANSEGYKEFKKYCCTAYNILRKHANLILNLFSLMVDANIPDIALEPDKAVLKVQEKFRLDLSDEEAEQ 320

                        330       340
                 ....*....|....*....|....*.
gi 809281416 795 YMQSLIDESVHALFAAVVEQIHKFAQ 820
Cdd:cd00896  321 YFQNLIDESVNALFPAVVETIHKIAQ 346
PI3Ka_III cd00870
Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is ...
 220-440 1.92e-86

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: 271.51  E-value: 1.92e-86
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 220 DHDLKPNAATRDQLNIIVSYPPTKQLTYEEQDLVWKFRYYLTNQEKALTKFLKCVNWDLPQEAKQALELLGKWKPMDVED 299
Cdd:cd00870    1 DKDLKPNSKERKELNKILKYPPTTKLTDEEKDLIWKFRFYLTNNKKALTKFLKSVNWSDEQEVKQALELMPKWAKIDIED 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 300 SLELLSSHYTNPTVRRYAVARLRQADDEDLLMYLLQLVQALKYENFDDIKngleptkkdsqssvsenvsnsginsaeids 379
Cdd:cd00870   81 ALELLSPYFTNPVVRKYAVSRLKLASDEELLLYLLQLVQALKYENLDLSP------------------------------ 130

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 809281416 380 sqiitsplpsvsspppasktkevpdGENLEQDLCTFLISRACKNSTLANYLYWYVIVECED 440
Cdd:cd00870  131 -------------------------LPRLDSPLADFLIERALKNPKLANFLYWYLKVELED 166
C2_PI3K_class_III cd08397
C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 24-123 5.23e-49

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: 170.12  E-value: 5.23e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  24 WNEWLKLPVKYPDLPRNAQVALTIWDVYGPGKAVPVGGTTVSLFGKYGMFRQGMHDLKVWPNVEADGSEPTKTPgrTSST 103
Cdd:cd08397   62 WNEWLTLPIKYSDLPRNSQLAITIWDVSGTGKAVPFGGTTLSLFNKDGTLRRGRQKLRVWPDVEADGSIPTSTG--KSPD 139

                         90       100
                 ....*....|....*....|
gi 809281416 104 LSEDQMSRLAKLTKAHRQGH 123
Cdd:cd08397  140 SERDELDRLEKLLKKYERGE 159
 
Name Accession Description Interval E-value
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 476-820 0e+00

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: 616.47  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 476 RSLLAAQQTFVDRLVHLMKAVQRESGNRKKKNERLQALLGDNEKMNLSDVELIPLPLEPQVKIRGIIPETATLFKSALMP 555
Cdd:cd00896    1 REALKRQQEFVDRLRSLMKEVKNEKGSRDKKIERLRELLSDSELGLLLFFEPLPLPLDPSVKVTGIIPEKSTVFKSALMP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 556 AQLFFKTEDGGKYPVIFKHGDDLRQDQLILQIISLMDKLLRKENLDLKLTPYKVLATSTKHGFMQFI-QSVPVAEVLDTE 634
Cdd:cd00896   81 LKLTFKTLDGGEYKVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVpNSKALADILKKY 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 635 GSIQNFFRKYAPSENGPNGISAEVMDTYVKSCAGYCVITYILGVGDRHLDNLLLTKTGKLFHIDFGYILGRDPKPLPPPM 714
Cdd:cd00896  161 GSILNFLRKHNPDESGPYGIKPEVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHIDFGYILGRDPKPFPPPM 240

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 715 KLNKEMVEGMGGTQSEQYQEFRKQCYTAFLHLRRYSNLILNLFSLMVDANIPDIALEPDKTVKKVQDKFRLDLSDEEAVH 794
Cdd:cd00896  241 KLCKEMVEAMGGANSEGYKEFKKYCCTAYNILRKHANLILNLFSLMVDANIPDIALEPDKAVLKVQEKFRLDLSDEEAEQ 320

                        330       340
                 ....*....|....*....|....*.
gi 809281416 795 YMQSLIDESVHALFAAVVEQIHKFAQ 820
Cdd:cd00896  321 YFQNLIDESVNALFPAVVETIHKIAQ 346
PI3Ka_III cd00870
Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is ...
 220-440 1.92e-86

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: 271.51  E-value: 1.92e-86
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 220 DHDLKPNAATRDQLNIIVSYPPTKQLTYEEQDLVWKFRYYLTNQEKALTKFLKCVNWDLPQEAKQALELLGKWKPMDVED 299
Cdd:cd00870    1 DKDLKPNSKERKELNKILKYPPTTKLTDEEKDLIWKFRFYLTNNKKALTKFLKSVNWSDEQEVKQALELMPKWAKIDIED 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 300 SLELLSSHYTNPTVRRYAVARLRQADDEDLLMYLLQLVQALKYENFDDIKngleptkkdsqssvsenvsnsginsaeids 379
Cdd:cd00870   81 ALELLSPYFTNPVVRKYAVSRLKLASDEELLLYLLQLVQALKYENLDLSP------------------------------ 130

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 809281416 380 sqiitsplpsvsspppasktkevpdGENLEQDLCTFLISRACKNSTLANYLYWYVIVECED 440
Cdd:cd00870  131 -------------------------LPRLDSPLADFLIERALKNPKLANFLYWYLKVELED 166
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 226-467 4.80e-69

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: 225.98  E-value: 4.80e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416   226 NAATRDQLNIIVSYPPTKQLTYEEQDLVWKFR-YYLTNQEKALTKFLKCVNWDLPQEAKQALELLGKWKPMDVEDSLELL 304
Cdd:smart00145   4 DIEEREQLEAILKLDPTYELTEEEKDLIWKFRhYYLTNNPKALPKFLLSVKWSDADEVAQALSLLLSWAPLDPEDALELL 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416   305 SSHYTNPTVRRYAVARLRQADDEDLLMYLLQLVQALKYENFDDikngleptkkdsqssvsenvsnsginsaeidssqiit 384
Cdd:smart00145  84 DPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLD------------------------------------- 126

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416   385 splpsvsspppasktkevpdgenleQDLCTFLISRACKNSTLANYLYWYVIVECEDQDTQQRDPKTHEMYLNVMRRFSQA 464
Cdd:smart00145 127 -------------------------SALARFLLERALANQRLGHFFYWYLKSELHDPHVSIRFGLLLEAYLRGCGTHLKE 181


                   ...
gi 809281416   465 LLK 467
Cdd:smart00145 182 LLK 184
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 570-772 2.62e-67

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: 223.33  E-value: 2.62e-67
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416   570 VIFKHGDDLRQDQLILQIISLMDKLLRKE----NLDLKLTPYKVLATSTKHGFMQFI-QSVPVAEVLDT----------- 633
Cdd:smart00146   1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVpNSTTLHEILKEyrkqkgkvldl 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416   634 ----------------------EGSIQNFFRKYAPSengPNGISAEVMDTYVKSCAGYCVITYILGVGDRHLDNLLLTKT 691
Cdd:smart00146  81 rsqtatrlkklelfleatgkfpDPVLYDWFTKKFPD---PSEDYFEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKT 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416   692 GKLFHIDFGYILGRDPKPLPPPMKL----NKEMVEGMGgtQSEQYQEFRKQCYTAFLHLRRYSNLILNLFSLMVDANIPD 767
Cdd:smart00146 158 GHLFHIDFGFILGNGPKLFGFPERVpfrlTPEMVDVMG--DSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLPD 235


                   ....*
gi 809281416   768 IALEP 772
Cdd:smart00146 236 WRSGK 240
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 568-768 1.30e-59

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: 202.56  E-value: 1.30e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  568 YPVIFKHGDDLRQDQLILQIISLMDKLLRKENLDLK-LTPYKVLATSTKHGFMQFIQ-SVPVAEVLD------------- 632
Cdd:pfam00454   2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLRrLKPYSVIPLGPKCGIIEWVPnSETLAYILDeygengvpptamv 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  633 -----------------------TEGSIQNFFRKYAPSENGPNgisaEVMDTYVKSCAGYCVITYILGVGDRHLDNLLL- 688
Cdd:pfam00454  82 kilhsalnypklklefesrislpPKVGLLQWFVKKSPDAEEWG----EARKNFVRSCAGYSVLDYILGNGDRHLDNILVd 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  689 TKTGKLFHIDFGYILGRDPKPLPPPMKL----NKEMVEGMGgtQSEQYQEFRKQCYTAFLHLRRYSNLILNLFSLMVDAN 764
Cdd:pfam00454 158 KTTGKLFHIDFGLCLPDAGKDLPFPEKVpfrlTREMVYAMG--PSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVADG 235


                  ....
gi 809281416  765 IPDI 768
Cdd:pfam00454 236 LPDW 239
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
504-821 9.33e-56

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 209.25  E-value: 9.33e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  504 KKKNERLQALLG---DNEKMNLSDVELIPLPLE-----PQVKIRGIIPETATLFKSALMPAQLFFKTEDGGKYPVIFKHG 575
Cdd:COG5032  1725 RKRLKRLLELRLkkvSPKLLLFHAFLEIKLPGQylldkPFVLIERFEPEVSVVKSHLQRPRRLTIRGSDGKLYSFIVKGG 1804

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  576 DDLRQDQLILQIISLMDKLLRKENL----DLKLTPYKVLATSTKHGFMQFIQSV-PVAEVLDT----------------- 633
Cdd:COG5032  1805 DDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGIIEWVPNSdTLHSILREyhkrknisidqekklaa 1884

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  634 -------EGSIQNFF---RKYAP------SENGPNGISAEV-MDTYVKSCAGYCVITYILGVGDRHLDNLLLTK-TGKLF 695
Cdd:COG5032  1885 rldnlklLLKDEFFTkatLKSPPvlydwfSESFPNPEDWLTaRTNFARSLAVYSVIGYILGLGDRHPGNILIDRsSGHVI 1964

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  696 HIDFGYILGRDPKPLPPPMK----LNKEMVEGMGGTQSEQYqeFRKQCYTAFLHLRRYSNLILNLFSLMVD------ANI 765
Cdd:COG5032  1965 HIDFGFILFNAPGRFPFPEKvpfrLTRNIVEAMGVSGVEGS--FRELCETAFRALRKNADSLMNVLELFVRdpliewRRL 2042

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 809281416  766 PDIALEPDKTVKKVQDKFRLDLSDEEAVHYMQSLIDESVHALFAAVVEQIHKFAQY 821
Cdd:COG5032  2043 PCFREIQNNEIVNVLERFRLKLSEKDAEKFVDLLINKSVESLITQATDPFQLATMY 2098
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 222-466 2.31e-51

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: 177.52  E-value: 2.31e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  222 DLKPNAATRDQLNIIVSYPPTKQLTYEEQDLVWKFRYYLTNQEKALTKFLKCVNWDLPQEAKQALELLGKWKPMDVEDSL 301
Cdd:pfam00613   2 DLKPNEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYLMLVPKALTKLLLSVKWSDLSEVAEALSLLLKWAPIDPVDAL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  302 ELLSSHYTNPTVRRYAVARLRQADDEDLLMYLLQLVQALKYENFDDikngleptkkdsqssvsenvsnsginsaeidssq 381
Cdd:pfam00613  82 ELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHD---------------------------------- 127

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  382 iitsplpsvsspppasktkevpdgenleQDLCTFLISRACKNSTLANYLYWYVIVECEDQDTQQRDPKTHEMYLnvmRRF 461
Cdd:pfam00613 128 ----------------------------SYLSRFLLQRALKNRRIGHFFFWYLKSEIHDEEVSPRFGSLLELYL---RSC 176


                  ....*
gi 809281416  462 SQALL 466
Cdd:pfam00613 177 GTSLL 181
C2_PI3K_class_III cd08397
C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 24-123 5.23e-49

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: 170.12  E-value: 5.23e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  24 WNEWLKLPVKYPDLPRNAQVALTIWDVYGPGKAVPVGGTTVSLFGKYGMFRQGMHDLKVWPNVEADGSEPTKTPgrTSST 103
Cdd:cd08397   62 WNEWLTLPIKYSDLPRNSQLAITIWDVSGTGKAVPFGGTTLSLFNKDGTLRRGRQKLRVWPDVEADGSIPTSTG--KSPD 139

                         90       100
                 ....*....|....*....|
gi 809281416 104 LSEDQMSRLAKLTKAHRQGH 123
Cdd:cd08397  140 SERDELDRLEKLLKKYERGE 159
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 24-135 2.24e-38

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: 139.42  E-value: 2.24e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416   24 WNEWLKLPVKYPDLPRNAQVALTIWDVYGPGKA-VPVGGTTVSLFGKYGMFRQGMHDLKVWPnveadgsePTKTPGRtss 102
Cdd:pfam00792  36 WNEWITFPIQISDLPRSARLCITIWDVSGPEKSfVPIGWVNTSLFDKKGILRQGKQKLRLWP--------SKSTPGR--- 104

                          90       100       110
                  ....*....|....*....|....*....|...
gi 809281416  103 tLSEDQMSRLAKLTKAHRQGHMVKVDWLDRLTF 135
Cdd:pfam00792 105 -SNVDEMNRLEKLLKKYERGQVSSVDWLDFLTF 136
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 24-60 4.76e-11

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 60.05  E-value: 4.76e-11
                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 809281416    24 WNEWLKLPVKYPDLPRNAQVALTIWDVYGPGKAVPVG 60
Cdd:smart00142  64 WNEWLTFPIQISDLPREARLCITIYAVKNPSKGSEFG 100
PTZ00303 PTZ00303
phosphatidylinositol kinase; Provisional
 534-703 2.01e-04

phosphatidylinositol kinase; Provisional


Pssm-ID: 140324 [Multi-domain]  Cd Length: 1374  Bit Score: 45.08  E-value: 2.01e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  534 PQVKIRGIIPETatLFKSalMPAQLFFktedggkypvIFKHgDDLRQDQLILQIISLMDKLLRKENLDLKLTPYKVLATS 613
Cdd:PTZ00303 1032 PVTAVNGVSPES--LHDS--LPQECMF----------LYKR-ENVERDQLMCISSRLLQMLLSSEIGNAEMLDYSVLPLS 1096

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  614 TKHGFMQFIQSVPVAEVLDTEGSIQNFFRKYAPSENgpngisaevmdtYVKSCAGYCVITYILGVGDRHLDNLLLTKTGK 693
Cdd:PTZ00303 1097 CDSGLIEKAEGRELSNLDNMDIASYVLYRGTRSCIN------------FLASAKLFLLLNYIFSIGDRHKGNVLIGTNGA 1164

                         170
                  ....*....|
gi 809281416  694 LFHIDFGYIL 703
Cdd:PTZ00303 1165 LLHIDFRFIF 1174
 
Name Accession Description Interval E-value
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 476-820 0e+00

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: 616.47  E-value: 0e+00
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 476 RSLLAAQQTFVDRLVHLMKAVQRESGNRKKKNERLQALLGDNEKMNLSDVELIPLPLEPQVKIRGIIPETATLFKSALMP 555
Cdd:cd00896    1 REALKRQQEFVDRLRSLMKEVKNEKGSRDKKIERLRELLSDSELGLLLFFEPLPLPLDPSVKVTGIIPEKSTVFKSALMP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 556 AQLFFKTEDGGKYPVIFKHGDDLRQDQLILQIISLMDKLLRKENLDLKLTPYKVLATSTKHGFMQFI-QSVPVAEVLDTE 634
Cdd:cd00896   81 LKLTFKTLDGGEYKVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVpNSKALADILKKY 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 635 GSIQNFFRKYAPSENGPNGISAEVMDTYVKSCAGYCVITYILGVGDRHLDNLLLTKTGKLFHIDFGYILGRDPKPLPPPM 714
Cdd:cd00896  161 GSILNFLRKHNPDESGPYGIKPEVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHIDFGYILGRDPKPFPPPM 240

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 715 KLNKEMVEGMGGTQSEQYQEFRKQCYTAFLHLRRYSNLILNLFSLMVDANIPDIALEPDKTVKKVQDKFRLDLSDEEAVH 794
Cdd:cd00896  241 KLCKEMVEAMGGANSEGYKEFKKYCCTAYNILRKHANLILNLFSLMVDANIPDIALEPDKAVLKVQEKFRLDLSDEEAEQ 320

                        330       340
                 ....*....|....*....|....*.
gi 809281416 795 YMQSLIDESVHALFAAVVEQIHKFAQ 820
Cdd:cd00896  321 YFQNLIDESVNALFPAVVETIHKIAQ 346
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 476-805 1.36e-106

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: 330.69  E-value: 1.36e-106
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 476 RSLLAAQQTFVDRLVHLMKAVQRESGNRKKknERLQALLGdnekmNLSDVELIPLPLEPQVKIRGIIPETATLFKSALMP 555
Cdd:cd00891    1 REELLKQVKVLDELKEIAKKIKEEPSEERK--EVLEKLLQ-----KLELPKKFTLPLDPRMEVKGLIVEKCKVMDSKKLP 73

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 556 AQLFFKTED--GGKYPVIFKHGDDLRQDQLILQIISLMDKLLRKENLDLKLTPYKVLATSTKHGFMQFIQ-SVPVAEVLD 632
Cdd:cd00891   74 LWLVFKNADpgGDPIKVIFKAGDDLRQDQLTLQLLRIMDKLWKKEGLDLRMTPYKCIATGDEVGMIEVVPnSETTAAIQK 153

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 633 TEG---------SIQNFFRKYAPSENgpngISAEVMDTYVKSCAGYCVITYILGVGDRHLDNLLLTKTGKLFHIDFGYIL 703
Cdd:cd00891  154 KYGgfgaafkdtPISNWLKKHNPTEE----EYEEAVENFIRSCAGYCVATYVLGIGDRHNDNIMVTKSGHLFHIDFGHFL 229

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 704 GRDPKPLPPPMKL-----NKEMVEGMGGTQSEQYQEFRKQCYTAFLHLRRYSNLILNLFSLMVDANIPDiaLEPDKTVKK 778
Cdd:cd00891  230 GNFKKKFGIKRERapfvfTPEMAYVMGGEDSENFQKFEDLCCKAYNILRKHGNLLINLFSLMLSAGIPE--LQSIEDIEY 307

                        330       340
                 ....*....|....*....|....*..
gi 809281416 779 VQDKFRLDLSDEEAVHYMQSLIDESVH 805
Cdd:cd00891  308 LRDALQLDLSDEEAAEHFRKLIHESLN 334
PI3Ka_III cd00870
Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is ...
 220-440 1.92e-86

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: 271.51  E-value: 1.92e-86
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 220 DHDLKPNAATRDQLNIIVSYPPTKQLTYEEQDLVWKFRYYLTNQEKALTKFLKCVNWDLPQEAKQALELLGKWKPMDVED 299
Cdd:cd00870    1 DKDLKPNSKERKELNKILKYPPTTKLTDEEKDLIWKFRFYLTNNKKALTKFLKSVNWSDEQEVKQALELMPKWAKIDIED 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 300 SLELLSSHYTNPTVRRYAVARLRQADDEDLLMYLLQLVQALKYENFDDIKngleptkkdsqssvsenvsnsginsaeids 379
Cdd:cd00870   81 ALELLSPYFTNPVVRKYAVSRLKLASDEELLLYLLQLVQALKYENLDLSP------------------------------ 130

                        170       180       190       200       210       220
                 ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 809281416 380 sqiitsplpsvsspppasktkevpdGENLEQDLCTFLISRACKNSTLANYLYWYVIVECED 440
Cdd:cd00870  131 -------------------------LPRLDSPLADFLIERALKNPKLANFLYWYLKVELED 166
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 226-467 4.80e-69

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: 225.98  E-value: 4.80e-69
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416   226 NAATRDQLNIIVSYPPTKQLTYEEQDLVWKFR-YYLTNQEKALTKFLKCVNWDLPQEAKQALELLGKWKPMDVEDSLELL 304
Cdd:smart00145   4 DIEEREQLEAILKLDPTYELTEEEKDLIWKFRhYYLTNNPKALPKFLLSVKWSDADEVAQALSLLLSWAPLDPEDALELL 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416   305 SSHYTNPTVRRYAVARLRQADDEDLLMYLLQLVQALKYENFDDikngleptkkdsqssvsenvsnsginsaeidssqiit 384
Cdd:smart00145  84 DPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLD------------------------------------- 126

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416   385 splpsvsspppasktkevpdgenleQDLCTFLISRACKNSTLANYLYWYVIVECEDQDTQQRDPKTHEMYLNVMRRFSQA 464
Cdd:smart00145 127 -------------------------SALARFLLERALANQRLGHFFYWYLKSELHDPHVSIRFGLLLEAYLRGCGTHLKE 181


                   ...
gi 809281416   465 LLK 467
Cdd:smart00145 182 LLK 184
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 485-820 5.14e-68

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: 229.10  E-value: 5.14e-68
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 485 FVDRLVHLMKAVQRESgNRKKKNERLQALLGDNEKMNlSDVELIP--LPLEPQVKIRGIIPETATLFKSALMPAQLFFKT 562
Cdd:cd05166    6 KQHVLVQALTSIAEKV-KSAKDSARENALRRELEQLA-SFLLENSfrLPLDPALEVTGVDVRSCSYFNSNALPLKLVFRN 83

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 563 ED--GGKYPVIFKHGDDLRQDQLILQIISLMDKLLRKENLDLKLTPYKVLATSTKHGFmqfIQSVPVAEVL---DTE--- 634
Cdd:cd05166   84 ADprAEPISVIFKVGDDLRQDMLTLQLIRIMDKIWLQEGLDLKMITFRCVPTGNKRGM---VELVPEAETLreiQTEhgl 160

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 635 -GS-----IQNFFRKYAPSEngPNGISAevMDTYVKSCAGYCVITYILGVGDRHLDNLLLTKTGKLFHIDFGYILG---- 704
Cdd:cd05166  161 tGSfkdrpLADWLQKHNPSE--LEYEKA--VENFIRSCAGYCVATYVLGICDRHNDNIMLKTSGHLFHIDFGKFLGdaqm 236

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 705 -----RDpkplPPPMKLNKEM--VEGMGGTQSEQYQEFRKQCYTAFLHLRRYSNLILNLFSLMVDANIPDIALEpdkTVK 777
Cdd:cd05166  237 fgnfkRD----RVPFVLTSDMayVINGGDKPSSRFQLFVDLCCQAFNIIRKNSNLLLNLLSLMLSSGIPGVTQD---DLR 309

                        330       340       350       360
                 ....*....|....*....|....*....|....*....|...
gi 809281416 778 KVQDKFRLDLSDEEAVHYMQSLIDESVHALFAAVVEQIHKFAQ 820
Cdd:cd05166  310 YVQDALLPELTDAEATAHFTRMIEESLSSKFTQLNFFIHNLAQ 352
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 478-805 2.45e-67

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: 227.90  E-value: 2.45e-67
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 478 LLAAQQTFVDRLVHLMKAVQRESGNRKKKNERLQALLGDNEKMN-LSDvelIPLPLEPQVKIRGIIPETATLFKSALMPA 556
Cdd:cd05165    3 SLSRQVEALNKLKKLSDILKEKKKSKEKVKKLLKECLKQKFYDEaLQN---FQSPLNPSHKLGELIIEKCKVMDSKKRPL 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 557 QLFFKTED-----GGKYPVIFKHGDDLRQDQLILQIISLMDKLLRKENLDLKLTPYKVLATSTKHGFMQFIQ-SVPVAEV 630
Cdd:cd05165   80 WLVFENADplalsGEDIKIIFKNGDDLRQDMLTLQIIRIMDNIWKEEGLDLRMLPYGCLSTGDNVGLIEVVRnAKTIANI 159

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 631 LDTEG----------SIQNFFRKYAPSENGPNgisaEVMDTYVKSCAGYCVITYILGVGDRHLDNLLLTKTGKLFHIDFG 700
Cdd:cd05165  160 QKKKGkvatlafnkdSLHKWLKEKNKTGEKYD----RAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVKENGQLFHIDFG 235

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 701 YILGRdpkpLPPPMKLNKEMV-------------EGMGGTQSEQYQEFRKQCYTAFLHLRRYSNLILNLFSLMVDANIPD 767
Cdd:cd05165  236 HFLGN----FKKKFGIKRERVpfvlthdfvyviaRGQDNTKSEEFQEFQELCEKAYLILRRHGNLFISLFSMMLSTGIPE 311

                        330       340       350
                 ....*....|....*....|....*....|....*...
gi 809281416 768 IALEPDktVKKVQDKFRLDLSDEEAVHYMQSLIDESVH 805
Cdd:cd05165  312 LTSVKD--IEYLRKTLALDKTEEEALKYFRKKFNEALK 347
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 570-772 2.62e-67

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: 223.33  E-value: 2.62e-67
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416   570 VIFKHGDDLRQDQLILQIISLMDKLLRKE----NLDLKLTPYKVLATSTKHGFMQFI-QSVPVAEVLDT----------- 633
Cdd:smart00146   1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVpNSTTLHEILKEyrkqkgkvldl 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416   634 ----------------------EGSIQNFFRKYAPSengPNGISAEVMDTYVKSCAGYCVITYILGVGDRHLDNLLLTKT 691
Cdd:smart00146  81 rsqtatrlkklelfleatgkfpDPVLYDWFTKKFPD---PSEDYFEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKT 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416   692 GKLFHIDFGYILGRDPKPLPPPMKL----NKEMVEGMGgtQSEQYQEFRKQCYTAFLHLRRYSNLILNLFSLMVDANIPD 767
Cdd:smart00146 158 GHLFHIDFGFILGNGPKLFGFPERVpfrlTPEMVDVMG--DSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLPD 235


                   ....*
gi 809281416   768 IALEP 772
Cdd:smart00146 236 WRSGK 240
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 568-768 1.30e-59

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: 202.56  E-value: 1.30e-59
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  568 YPVIFKHGDDLRQDQLILQIISLMDKLLRKENLDLK-LTPYKVLATSTKHGFMQFIQ-SVPVAEVLD------------- 632
Cdd:pfam00454   2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLRrLKPYSVIPLGPKCGIIEWVPnSETLAYILDeygengvpptamv 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  633 -----------------------TEGSIQNFFRKYAPSENGPNgisaEVMDTYVKSCAGYCVITYILGVGDRHLDNLLL- 688
Cdd:pfam00454  82 kilhsalnypklklefesrislpPKVGLLQWFVKKSPDAEEWG----EARKNFVRSCAGYSVLDYILGNGDRHLDNILVd 157

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  689 TKTGKLFHIDFGYILGRDPKPLPPPMKL----NKEMVEGMGgtQSEQYQEFRKQCYTAFLHLRRYSNLILNLFSLMVDAN 764
Cdd:pfam00454 158 KTTGKLFHIDFGLCLPDAGKDLPFPEKVpfrlTREMVYAMG--PSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVADG 235


                  ....
gi 809281416  765 IPDI 768
Cdd:pfam00454 236 LPDW 239
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
 537-822 6.39e-57

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: 197.43  E-value: 6.39e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 537 KIRGIIPETATLFKSAL-MPAQLFFKTEDGGK-----------------YPVIFKHGDDLRQDQLILQIISLMDKLLRKE 598
Cdd:cd05167    1 VVLGIDYKSGKPLQSAAkAPFLVTFKVKDCGVdelehegteseatkevwQAAIFKVGDDCRQDMLALQLISLFKNIFEEV 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 599 NLDLKLTPYKVLATSTKHGfmqFIQSVPVAEVLD-----TEGSIQNFFR-KYAPsENGPNGISAEvmDTYVKSCAGYCVI 672
Cdd:cd05167   81 GLDLYLFPYRVVATGPGCG---VIEVIPNSKSRDqigreTDNGLYEYFLsKYGD-ESTPAFQKAR--RNFIKSMAGYSLV 154

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 673 TYILGVGDRHLDNLLLTKTGKLFHIDFGYIL----GRDPKPLPPPMKLNKEMVEGMGGT-QSEQYQEFRKQCYTAFLHLR 747
Cdd:cd05167  155 SYLLQIKDRHNGNIMIDDDGHIIHIDFGFIFeispGGNLGFESAPFKLTKEMVDLMGGSmESEPFKWFVELCVRGYLAVR 234

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 809281416 748 RYSNLILNLFSLMVDANIPDIAlepDKTVKKVQDKFRLDLSDEEAVHYMQSLIDESVHALFAAVVEQIhkfaQYW 822
Cdd:cd05167  235 PYAEAIVSLVELMLDSGLPCFR---GQTIKNLRERFALEMSEREAANFMIKLIADSYLKIRTKGYDMF----QYY 302
PI3Ka cd00864
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 227-440 9.67e-57

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: 191.27  E-value: 9.67e-57
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 227 AATRDQLNIIVSYPPTKQLTYEEQDLVWKFRYYLTNQEKALTKFLKCVNWDLPQEAKQALELLGKWKPMDVEDSLELLSS 306
Cdd:cd00864    1 AWERKPLLAILLYPPFSTLTEEEKELLWKFRYYLLNVPKALPKLLKSVNWNDDEEVSELYQLLKWWAPLSPEDALELLSP 80

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 307 HYTNPTVRRYAVARLRQADDEDLLMYLLQLVQALKYENFDDikngleptkkdsqssvsenvsnsginsaeidssqiitsp 386
Cdd:cd00864   81 KYPDPVVRQYAVRVLESASDDELLLYLPQLVQALKYEPYLD--------------------------------------- 121

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....
gi 809281416 387 lpsvsspppasktkevpdgenleQDLCTFLISRACKNSTLANYLYWYVIVECED 440
Cdd:cd00864  122 -----------------------SYLARFLLERALKSQRLGHQLYWNLKSEIHD 152
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
504-821 9.33e-56

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 209.25  E-value: 9.33e-56
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  504 KKKNERLQALLG---DNEKMNLSDVELIPLPLE-----PQVKIRGIIPETATLFKSALMPAQLFFKTEDGGKYPVIFKHG 575
Cdd:COG5032  1725 RKRLKRLLELRLkkvSPKLLLFHAFLEIKLPGQylldkPFVLIERFEPEVSVVKSHLQRPRRLTIRGSDGKLYSFIVKGG 1804

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  576 DDLRQDQLILQIISLMDKLLRKENL----DLKLTPYKVLATSTKHGFMQFIQSV-PVAEVLDT----------------- 633
Cdd:COG5032  1805 DDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGIIEWVPNSdTLHSILREyhkrknisidqekklaa 1884

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  634 -------EGSIQNFF---RKYAP------SENGPNGISAEV-MDTYVKSCAGYCVITYILGVGDRHLDNLLLTK-TGKLF 695
Cdd:COG5032  1885 rldnlklLLKDEFFTkatLKSPPvlydwfSESFPNPEDWLTaRTNFARSLAVYSVIGYILGLGDRHPGNILIDRsSGHVI 1964

                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  696 HIDFGYILGRDPKPLPPPMK----LNKEMVEGMGGTQSEQYqeFRKQCYTAFLHLRRYSNLILNLFSLMVD------ANI 765
Cdd:COG5032  1965 HIDFGFILFNAPGRFPFPEKvpfrLTRNIVEAMGVSGVEGS--FRELCETAFRALRKNADSLMNVLELFVRdpliewRRL 2042

                         330       340       350       360       370
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 809281416  766 PDIALEPDKTVKKVQDKFRLDLSDEEAVHYMQSLIDESVHALFAAVVEQIHKFAQY 821
Cdd:COG5032  2043 PCFREIQNNEIVNVLERFRLKLSEKDAEKFVDLLINKSVESLITQATDPFQLATMY 2098
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 522-820 2.30e-51

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: 184.10  E-value: 2.30e-51
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 522 LSDVELiplPLEPQVKIRGIIPETATLFKSALMPAQLFFKTED--GGKYPVIFKHGDDLRQDQLILQIISLMDKLLRKEN 599
Cdd:cd05174   53 LSHLQS---PLDPSIILEEVCVDQCTFMDSKMKPLWIMYSSEEagAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEG 129

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 600 LDLKLTPYKVLATSTKHGFMQFIQSVpvaevlDTEGSIQ---------NFFRKYA-----PSENgPNGISAEVMDTYVKS 665
Cdd:cd05174  130 LDLRMTPYGCLSTGDKTGLIEVVLHS------DTIANIQlnksnmaatAAFNKDAllnwlKSKN-PGDALDQAIEEFTLS 202

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 666 CAGYCVITYILGVGDRHLDNLLLTKTGKLFHIDFGYILGRdpkpLPPPMKLNKEMVEGM-----------GGT-QSEQYQ 733
Cdd:cd05174  203 CAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGN----FKTKFGINRERVPFIltydfvhviqqGKTnNSEKFE 278

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 734 EFRKQCYTAFLHLRRYSNLILNLFSLMVDANIPDiaLEPDKTVKKVQDKFRLDLSDEEAVHYMQSLIDESVHALFAAVVE 813
Cdd:cd05174  279 RFRGYCERAYTILRRHGLLFLHLFALMKAAGLPE--LSCSKDIQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVN 356


                 ....*...
gi 809281416 814 QI-HKFAQ 820
Cdd:cd05174  357 WLaHNVSK 364
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 222-466 2.31e-51

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: 177.52  E-value: 2.31e-51
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  222 DLKPNAATRDQLNIIVSYPPTKQLTYEEQDLVWKFRYYLTNQEKALTKFLKCVNWDLPQEAKQALELLGKWKPMDVEDSL 301
Cdd:pfam00613   2 DLKPNEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYLMLVPKALTKLLLSVKWSDLSEVAEALSLLLKWAPIDPVDAL 81

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  302 ELLSSHYTNPTVRRYAVARLRQADDEDLLMYLLQLVQALKYENFDDikngleptkkdsqssvsenvsnsginsaeidssq 381
Cdd:pfam00613  82 ELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHD---------------------------------- 127

                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  382 iitsplpsvsspppasktkevpdgenleQDLCTFLISRACKNSTLANYLYWYVIVECEDQDTQQRDPKTHEMYLnvmRRF 461
Cdd:pfam00613 128 ----------------------------SYLSRFLLQRALKNRRIGHFFFWYLKSEIHDEEVSPRFGSLLELYL---RSC 176


                  ....*
gi 809281416  462 SQALL 466
Cdd:pfam00613 177 GTSLL 181
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 499-820 4.29e-50

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: 180.09  E-value: 4.29e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 499 ESGNRKKKNERLQALLGDNEKMnLSDVELIPLPLEPQVKIRGIIPETATLFKSALMPAQLFFKTED--GGKYPVIFKHGD 576
Cdd:cd05177   22 KTASDTRRKEVLKREASRLEDF-FQDVVSCCLPLNPALRVKGIDADACSYFTSNAAPLKISFINANplAKNISIIFKTGD 100

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 577 DLRQDQLILQIISLMDKLLRKENLDLKLTPYKVLATSTKHGFMQFI-QSVPVAEVLDTEGSI----QNFFRKYAPSENGP 651
Cdd:cd05177  101 DLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYRCLSTGKTQGLVQMVpDAVTLAKIHRESGLIgplkENTIEKWFHMHNKL 180

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 652 NGISAEVMDTYVKSCAGYCVITYILGVGDRHLDNLLLTKTGKLFHIDFGYILG---------RDPKPLPPPMKLNKEMVE 722
Cdd:cd05177  181 KEDYDKAVRNFFHSCAGWCVVTFILGVCDRHNDNIMLTHSGHMFHIDFGKFLGhaqtfgsikRDRAPFIFTSEMEYFITE 260

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 723 gmGGTQSEQYQEFRKQCYTAFLHLRRYSNLILNLFSLMVDANIPDiaLEPDKTVKKVQDKFRLDLSDEEAVHYMQSLIDE 802
Cdd:cd05177  261 --GGKKPQRFQRFVELCCRAYNIVRKHSQLLLNLLEMMLHAGLPE--LKDIQDLKYVYNNLRPQDTDLEATSYFTKKIKE 336

                        330
                 ....*....|....*...
gi 809281416 803 SVHALFAAVVEQIHKFAQ 820
Cdd:cd05177  337 SLECFPVKLNNLIHTLAQ 354
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
 569-807 7.67e-50

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: 177.29  E-value: 7.67e-50
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 569 PVIFKHGDDLRQDQLILQIISLMDKLLRKENLDLKLTPYKVLATSTKHGFMQFIqsvPVAEVLDT-------EGSIQNFF 641
Cdd:cd05168   32 SVIVKSGDDLRQELLAMQLIKQFQRIFEEAGLPLWLRPYEILVTSSDSGLIETI---PDTVSIDSlkkrfpnFTSLLDYF 108

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 642 RKYAPSENGPNGISAevMDTYVKSCAGYCVITYILGVGDRHLDNLLLTKTGKLFHIDFGYILGrdpkplpppmklN---- 717
Cdd:cd05168  109 ERTFGDPNSERFKEA--QRNFVESLAAYSLVCYLLQIKDRHNGNILLDSEGHIIHIDFGFMLS------------Nspgg 174

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 718 -----------KEMVEGMGGTQSEQYQEFRKQCYTAFLHLRRYSNLILNLFSLMVDAN-IPDIALEPDKTVKKVQDKFRL 785
Cdd:cd05168  175 lgfetapfkltQEYVEVMGGLESDMFRYFKTLMIQGFLALRKHADRIVLLVEIMQQGSkLPCFFGGGEFTIEQLRERFKL 254

                        250       260
                 ....*....|....*....|..
gi 809281416 786 DLSDEEAVHYMQSLIDESVHAL 807
Cdd:cd05168  255 NLTEEECAQFVDSLIDKSLNNW 276
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 502-804 2.07e-49

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: 178.23  E-value: 2.07e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 502 NRKKKNERLQALLGDNE-KMNLSDVELiplPLEPQVKIRGIIPETATLFKSALMPAQLFFKTE--DGGKYPVIFKHGDDL 578
Cdd:cd05173   29 SKAKGKEAMHTCLRQSAyREALSDLQS---PLNPSIILSELNVEKCKYMDSKMKPLWIVYNNKlfGGDSLGIIFKNGDDL 105

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 579 RQDQLILQIISLMDKLLRKENLDLKLTPYKVLATSTKHGFMQFIQSV-PVAEV-LDT----------EGSIQNFFRKYAP 646
Cdd:cd05173  106 RQDMLTLQILRLMDTLWKEAGLDLRIVPYGCLATGDRSGLIEVVSSAeTIADIqLNSsnvaaaaafnKDALLNWLKEYNS 185

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 647 SENGPNGIsaevmDTYVKSCAGYCVITYILGVGDRHLDNLLLTKTGKLFHIDFGYILG---------RDPKPLPPPMKLN 717
Cdd:cd05173  186 GDDLERAI-----EEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGnfkskfgikRERVPFILTYDFI 260

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 718 KEMVEGMGGtQSEQYQEFRKQCYTAFLHLRRYSNLILNLFSLMVDANIPDiaLEPDKTVKKVQDKFRLDLSDEEAVHYMQ 797
Cdd:cd05173  261 HVIQQGKTG-NTEKFGRFRQYCEDAYLILRKNGNLFITLFALMLTAGLPE--LTSVKDIQYLKDSLALGKSEEEALKQFR 337


                 ....*..
gi 809281416 798 SLIDESV 804
Cdd:cd05173  338 QKFDEAL 344
C2_PI3K_class_III cd08397
C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 24-123 5.23e-49

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: 170.12  E-value: 5.23e-49
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  24 WNEWLKLPVKYPDLPRNAQVALTIWDVYGPGKAVPVGGTTVSLFGKYGMFRQGMHDLKVWPNVEADGSEPTKTPgrTSST 103
Cdd:cd08397   62 WNEWLTLPIKYSDLPRNSQLAITIWDVSGTGKAVPFGGTTLSLFNKDGTLRRGRQKLRVWPDVEADGSIPTSTG--KSPD 139

                         90       100
                 ....*....|....*....|
gi 809281416 104 LSEDQMSRLAKLTKAHRQGH 123
Cdd:cd08397  140 SERDELDRLEKLLKKYERGE 159
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
 569-804 7.35e-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: 171.68  E-value: 7.35e-48
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 569 PVIFKHGDDLRQDQLILQIISLMDKLLRKENLDLKLTPYKVLATSTKHGFMQFIQSV----PVAEVLDTEG---SIQNFF 641
Cdd:cd00893   29 SLIVKTGDDLKQEQLALQLISQFDQIFKEEGLPLWLRPYEILSLGPDSGIIEMIKNAvsidSLKKKLDSFNkfvSLSDFF 108

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 642 RKYAPSENGPNGIsaevmDTYVKSCAGYCVITYILGVGDRHLDNLLLTKTGKLFHIDFGYILGRDPKPLPPPMKLNK--- 718
Cdd:cd00893  109 DDNFGDEAIQKAR-----DNFLQSLVAYSLVCYFLQIKDRHNGNILLDKEGHIIHIDFGFFLSSHPGFYGFEGAPFKlss 183

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 719 EMVEGMGGTQSEQYQEFRKQCYTAFLHLRRYSNLILNLFSLMVDANIPDIALEpdKTVKKVQDKFRLDLSDEEAVHYMQS 798
Cdd:cd00893  184 EYIEVLGGVDSELFKEFRKLFLKGFMALRKHSDKILSLVEMMYSGHGITCFGK--KTIQQLKQRFNPELTEGELEVYVLS 261


                 ....*.
gi 809281416 799 LIDESV 804
Cdd:cd00893  262 LINKSL 267
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 530-799 5.41e-47

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: 171.59  E-value: 5.41e-47
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 530 LPLEPQVKIRGIIPETATLFKSALMPAQLFFKTEDGGKYP-----VIFKHGDDLRQDQLILQIISLMDKLLRKENLDLKL 604
Cdd:cd00894   57 VPYDPGLRAGALVIEKCKVMASKKKPLWLEFKCADPTALSnetigIIFKHGDDLRQDMLILQILRIMESIWETESLDLCL 136

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 605 TPYKVLATSTKHGFMQFIQ-SVPVAEVLDTEGSIQNFFRKYAPS----ENGPNGIS-AEVMDTYVKSCAGYCVITYILGV 678
Cdd:cd00894  137 LPYGCISTGDKIGMIEIVKdATTIAKIQQSTVGNTGAFKDEVLNhwlkEKCPIEEKfQAAVERFVYSCAGYCVATFVLGI 216

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 679 GDRHLDNLLLTKTGKLFHIDFGYILGRdpkpLPPPMKLNKEMVE------------GMGGTQSEQYQEFRKQCYTAFLHL 746
Cdd:cd00894  217 GDRHNDNIMITETGNLFHIDFGHILGN----YKSFLGINKERVPfvltpdflfvmgTSGKKTSLHFQKFQDVCVKAYLAL 292

                        250       260       270       280       290
                 ....*....|....*....|....*....|....*....|....*....|....
gi 809281416 747 RRYSNLILNLFSLMVDANIPDIALEPDktVKKVQDKFRLDLSDEEAV-HYMQSL 799
Cdd:cd00894  293 RHHTNLLIILFSMMLMTGMPQLTSKED--IEYIRDALTVGKSEEDAKkHFLDQI 344
PI3Kc_C2_alpha cd05176
Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 476-820 1.21e-43

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: 161.69  E-value: 1.21e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 476 RSLLAAQQTFVDRLVHLMKAVQRESGNRKKKN-----ERLQALLGDNEkmnlsdvelIPLPLEPQVKIRGIIPETATLFK 550
Cdd:cd05176    1 REELEKQTRLVQLLGRVAEKVRQASGSARQVAlqdgmERVQSFFQKNK---------CRLPLSPSLVAKELNIKACSFFS 71

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 551 SALMPAQLFFKTED--GGKYPVIFKHGDDLRQDQLILQIISLMDKLLRKENLDLKLTPYKVLATSTKHGFMQFIQSVPVA 628
Cdd:cd05176   72 SNAVPLKVALVNADplGEEINVMFKVGEDLRQDMLALQMIKIMDKIWLQEGLDLRMVIFKCLSTGKDRGMVELVPSSDTL 151

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 629 EVLDTE----GSIQN-----FFRKYAPSENGpngiSAEVMDTYVKSCAGYCVITYILGVGDRHLDNLLLTKTGKLFHIDF 699
Cdd:cd05176  152 RKIQVEygvtGSFKDkplaeWLRKYNPSEEE----YEKASENFIYSCAGCCVATYVLGICDRHNDNIMLRSTGHMFHIDF 227

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 700 GYILG---------RDpkPLPPPMKLNKEMVEGMGGTQSEQYQEFRKQCYTAFLHLRRYSNLILNLFSLMVDANIPDIAL 770
Cdd:cd05176  228 GKFLGhaqmfgsfkRD--RAPFVLTSDMAYVINGGEKPTIRFQLFVDLCCQAYNLIRKHTNLFLNLLSLMLSSGLPELTG 305

                        330       340       350       360       370
                 ....*....|....*....|....*....|....*....|....*....|
gi 809281416 771 EPDktVKKVQDKFRLDLSDEEAVHYMQSLIDESVHALFAAVVEQIHKFAQ 820
Cdd:cd05176  306 IQD--LKYVFDALQPQTTDAEATIFFTRLIESSLGSVATKFNFFIHNLAQ 353
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 530-820 3.76e-43

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: 160.55  E-value: 3.76e-43
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 530 LPLEPQVKIRGIIPETATLFKSALMPAQLFFKTED--GGKYPVIFKHGDDLRQDQLILQIISLMDKLLRKENLDLKLTPY 607
Cdd:cd00895   52 LPLSPSLLVKGIVPRDCSYFNSNAVPLKLSFQNVDplGENIRVIFKCGDDLRQDMLTLQMIRIMNKIWVQEGLDMRMVIF 131

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 608 KVLATSTKHGFMQFIQSVPVAEVLDTEGSIQNFFR---------KYAPSENGpngiSAEVMDTYVKSCAGYCVITYILGV 678
Cdd:cd00895  132 RCFSTGRGRGMVEMIPNAETLRKIQVEHGVTGSFKdrpladwlqKHNPTEDE----YEKAVENFIYSCAGCCVATYVLGI 207

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 679 GDRHLDNLLLTKTGKLFHIDFGYILG---------RDpkPLPPPMKLNKEMVEGMGGTQSEQYQEFRKQCYTAFLHLRRY 749
Cdd:cd00895  208 CDRHNDNIMLKTTGHMFHIDFGRFLGhaqmfgnikRD--RAPFVFTSDMAYVINGGDKPSSRFHDFVDLCCQAYNLIRKH 285

                        250       260       270       280       290       300       310
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 809281416 750 SNLILNLFSLMVDANIPDIALEPDktVKKVQDKFRLDLSDEEAVHYMQSLIDESVHALFAAVVEQIHKFAQ 820
Cdd:cd00895  286 THLFLNLLGLMLSCGIPELSDLED--LKYVYDALRPQDTEADATTYFTRLIESSLGSVATKLNFFIHNLAQ 354
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 24-135 2.24e-38

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: 139.42  E-value: 2.24e-38
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416   24 WNEWLKLPVKYPDLPRNAQVALTIWDVYGPGKA-VPVGGTTVSLFGKYGMFRQGMHDLKVWPnveadgsePTKTPGRtss 102
Cdd:pfam00792  36 WNEWITFPIQISDLPRSARLCITIWDVSGPEKSfVPIGWVNTSLFDKKGILRQGKQKLRLWP--------SKSTPGR--- 104

                          90       100       110
                  ....*....|....*....|....*....|...
gi 809281416  103 tLSEDQMSRLAKLTKAHRQGHMVKVDWLDRLTF 135
Cdd:pfam00792 105 -SNVDEMNRLEKLLKKYERGQVSSVDWLDFLTF 136
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 479-806 1.05e-36

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: 142.12  E-value: 1.05e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 479 LAAQQTFVDRLVHLMKAVQRESGNRKKKNErLQALLGDNEKMNLSD-VELIPLPLEPQVKIRGIIPETATLFKSALMP-- 555
Cdd:cd05175    8 LSRQVEAMEKLINLTDILKQEKKDETQKVQ-MKFLVEQMRRPDFMDaLQGFLSPLNPAHQLGNLRLEECRIMSSAKRPlw 86

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 556 ---------AQLFFKTEDggkypVIFKHGDDLRQDQLILQIISLMDKLLRKENLDLKLTPYKVLATSTKHGFMQFIQSVP 626
Cdd:cd05175   87 lnwenpdimSELLFQNNE-----IIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSH 161

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 627 VAEVLDTEGSIQNFFRKYAPS------ENGPNGISAEVMDTYVKSCAGYCVITYILGVGDRHLDNLLLTKTGKLFHIDFG 700
Cdd:cd05175  162 TIMQIQCKGGLKGALQFNSHTlhqwlkDKNKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFG 241

                        250       260       270       280       290       300       310       320
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 701 YIL-------GRDPKPLPPPMKLNKEMVEGMGG---TQSEQYQEFRKQCYTAFLHLRRYSNLILNLFSLMVDANIPDiaL 770
Cdd:cd05175  242 HFLdhkkkkfGYKRERVPFVLTQDFLIVISKGAqecTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPE--L 319

                        330       340       350
                 ....*....|....*....|....*....|....*.
gi 809281416 771 EPDKTVKKVQDKFRLDLSDEEAVHYMQSLIDESVHA 806
Cdd:cd05175  320 QSFDDIAYIRKTLALDKTEQEALEYFMKQMNDAHHG 355
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
 555-762 5.57e-36

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: 135.54  E-value: 5.57e-36
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 555 PAQLFFKTEDGGKYPVIFKHGDDLRQDQLILQIISLMDKLLRKENLDLKLTPYKVLATSTKHGFmqfIQSVPVAEVLdtE 634
Cdd:cd00142   17 PKKITLIGADGKTYSFLLKRRDDLRKDERSFQFMRLIQSILEKESVNLVLPPYKVIPLSENSGL---IEIVKDAQTI--E 91

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 635 GSIQNFFRKyAPSENGpngiSAEVMDTYVKSCAGYCVITYILGVGDRHLDNLLLTKTGKLFHIDFGYILGRDPKPLPPPM 714
Cdd:cd00142   92 DLLKSLWRK-SPSSQS----WLNRRENFSCSLAGYSVLGYIFGIGDRHPSNIMIEPSGNIFHIDFGFIFSGRKLAEGVET 166

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|.
gi 809281416 715 KL---NKEMVEGMGGTQSEQYqeFRKQCYTAFLHLRRYSNLILNLFSLMVD 762
Cdd:cd00142  167 VPfrlTPMLENAMGTAGVNGP--FQISMVKIMEILREHADLIVPILEHSLR 215
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 230-347 8.68e-33

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: 124.73  E-value: 8.68e-33
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 230 RDQLNIIVSYPPTKQLTYEEQDLVWKFRYYLTNQEKALTKFLKCVNWDLPQEAKQALELLGKWKPMDVEDSLELLSSHYT 309
Cdd:cd00872    4 REQLEAIIARDPLSELTEEDKELLWKLRHECRKKPQALPKLLLSVKWNKRDDVAQMYQLLKRWPKLKPEQALELLDCNFP 83

                         90       100       110
                 ....*....|....*....|....*....|....*...
gi 809281416 310 NPTVRRYAVARLRQADDEDLLMYLLQLVQALKYENFDD 347
Cdd:cd00872   84 DEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHD 121
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
 538-761 1.43e-27

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


Pssm-ID: 270708 [Multi-domain]  Cd Length: 222  Bit Score: 111.21  E-value: 1.43e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 538 IRGIIPETaTLFKSALMPAQLFFKTEDGGKYPVIFKHGDDLRQDQLILQIISLMDKLLRKEN----LDLKLTPYKVLATS 613
Cdd:cd05164    1 IASFDPRV-RILASLQKPKKITILGSDGKEYPFLVKGDDDLRKDERVMQLFQLLNTLLEKDKetrkRNLTIRTYSVVPLS 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 614 TKHGFMQFI-QSVPVAEVLDtegsiQNFFRKYAPSEngpngISAEVMDTYVKSCAGYCVITYILGVGDRHLDNLLL-TKT 691
Cdd:cd05164   80 SQSGLIEWVdNTTTLKPVLK-----KWFNETFPDPT-----QWYEARSNYTKSTAVMSMVGYIIGLGDRHLENILIdTKT 149

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 809281416 692 GKLFHIDFGYILGRDPKPLPPPMK---LNKEMVEGMGGTQSEqyQEFRKQCYTAFLHLRRYSNLILNLFSLMV 761
Cdd:cd05164  150 GEVVHIDFGMIFNKGKTLPVPEIVpfrLTRNIINGMGPTGVE--GLFRKSCEQVLRVFRKHKDKLITFLDTFL 220
PIKKc_DNA-PK cd05172
Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, ...
 544-704 3.18e-27

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: 110.74  E-value: 3.18e-27
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 544 ETATLFKSALMPAQLFFKTEDGGKYPVIFKHGDDLRQDQLILQIISLMDKLLRKE----NLDLKLTPYKVLATSTKHGFM 619
Cdd:cd05172    6 PRVLVLSSKRRPKRITIRGSDEKEYKFLVKGGEDLRQDQRIQQLFDVMNNILASDpacrQRRLRIRTYQVIPMTSRLGLI 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 620 QFIQ-SVPVAEVLdTEGSIQNFFRKYAPsengpngiSAE----VMDTYVKSCAGYCVITYILGVGDRHLDNLLL-TKTGK 693
Cdd:cd05172   86 EWVDnTTPLKEIL-ENDLLRRALLSLAS--------SPEaflaLRSNFARSLAAMSICGYILGIGDRHLSNFLVdLSTGR 156

                        170
                 ....*....|.
gi 809281416 694 LFHIDFGYILG 704
Cdd:cd05172  157 LIGIDFGHAFG 167
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
 564-754 2.39e-22

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: 98.00  E-value: 2.39e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 564 DGGKYPVIFKHGDDLRQDQLILQIISLMDKLLRKE----NLDLKLTPYKVLATSTKHGFMQFIQ-SVPVAEVLDTEGSIQ 638
Cdd:cd05171   26 DGKKYKQLVKGGDDLRQDAVMEQVFELVNQLLKRDketrKRKLRIRTYKVVPLSPRSGVLEFVEnTIPLGEYLVGASSKS 105

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 639 NFFRKYAPSENGPNGISAEVMD-------------------------------------------TYVKSCAGYCVITYI 675
Cdd:cd05171  106 GAHARYRPKDWTASTCRKKMREkakasaeerlkvfdeicknfkpvfrhfflekfpdpsdwferrlAYTRSVATSSIVGYI 185

                        170       180       190       200       210       220       230       240
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 676 LGVGDRHLDNLLL-TKTGKLFHIDFGYI----------------LGRDpkplpppmklnkeMVEGMGGTQSEqyQEFRKQ 738
Cdd:cd05171  186 LGLGDRHLNNILIdQKTGELVHIDLGIAfeqgkllpipetvpfrLTRD-------------IVDGMGITGVE--GVFRRC 250

                        250
                 ....*....|....*.
gi 809281416 739 CYTAFLHLRRYSNLIL 754
Cdd:cd05171  251 CEETLRVLRENKEALL 266
C2_PI3K_like cd08380
C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes ...
 24-123 4.66e-22

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: 93.19  E-value: 4.66e-22
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  24 WNEWLKLPVKYPDLPRNAQVALTIWDVYGPG--KAVPVGGTTVSLFGKYGMFRQGMHDLKVWPNVEADGSEPTktpgrTS 101
Cdd:cd08380   60 WNEWLTFDILISDLPREARLCLSIYAVSEPGskKEVPLGWVNVPLFDYKGKLRQGMITLNLWPGKKTDPRIAC-----TP 134

                         90       100
                 ....*....|....*....|..
gi 809281416 102 STLSEDQMSRLAKLTKAHRQGH 123
Cdd:cd08380  135 CNNSNENSTRLLIELPEFSKPV 156
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 544-762 1.07e-19

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


Pssm-ID: 270625 [Multi-domain]  Cd Length: 237  Bit Score: 89.10  E-value: 1.07e-19
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 544 ETATLFKSALMPAQLFFKTEDGGKYPVIFKHGDDLRQDQLILQIISLMDKLLRK----ENLDLKLTPYKVLATSTKHGFM 619
Cdd:cd00892    6 DEVEIMPSLQKPKKITLVGSDGKKYPFLCKPKDDLRKDARMMEFNTLINRLLSKdpesRRRNLHIRTYAVIPLNEECGII 85

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 620 QFIQ-SVPVAEVLDTEGS--IQNFFRKYAPSengpngISA--EVMDTYVKSCAGYCVITYILGVGDRHLDNLLL-TKTGK 693
Cdd:cd00892   86 EWVPnTVTLRSILSTLYPpvLHEWFLKNFPD------PTAwyEARNNYTRSTAVMSMVGYILGLGDRHGENILFdSTTGD 159

                        170       180       190       200       210       220       230
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 809281416 694 LFHIDFGYILGRDPKPLPppmklnKE---------MVEGMGGTQSEqyQEFRKQCYTAFLHLRRYSNLILN-LFSLMVD 762
Cdd:cd00892  160 VVHVDFDCLFDKGLTLEV------PErvpfrltqnMVDAMGVTGVE--GTFRRTCEVTLRVLRENRETLMSvLETFVHD 230
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 538-700 8.93e-16

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: 78.29  E-value: 8.93e-16
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 538 IRGIIPeTATLFKSALMPAQLFFKTEDGGKYPVIFKHGDDLRQDQLILQIISLMDKLLRKENL----DLKLTPYKVLATS 613
Cdd:cd05169    1 ISSFDP-TLEVITSKQRPRKLTIVGSDGKEYKFLLKGHEDLRLDERVMQLFGLVNTLLKNDSEtsrrNLSIQRYSVIPLS 79

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 614 TKHGFMQFIQ----------------SVPV-AEVLDTEGSIQNFFR----------KYApSENGPNGISAEVM------- 659
Cdd:cd05169   80 PNSGLIGWVPgcdtlhslirdyrekrKIPLnIEHRLMLQMAPDYDNltliqkvevfEYA-LENTPGDDLRRVLwlkspss 158

                        170       180       190       200
                 ....*....|....*....|....*....|....*....|....*....
gi 809281416 660 -------DTYVKSCAGYCVITYILGVGDRHLDNLLL-TKTGKLFHIDFG 700
Cdd:cd05169  159 eawlerrTNFTRSLAVMSMVGYILGLGDRHPSNIMLdRLTGKVIHIDFG 207
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
 242-343 1.21e-15

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: 75.57  E-value: 1.21e-15
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 242 TKQLTY----EEQDLVWKFRYYLTNQEKALTKFLKCV-NWDLPQEAKqALELLGKWKPMDVEDSLELLSSHYTNPTVRRY 316
Cdd:cd00869   12 QKQSTYtlstEDKDLLWEKRLYCTNEPNALPLVLASApSWDWANLMD-VYQLLHQWAPLRPLIALELLLPKFPDQEVRAH 90

                         90       100
                 ....*....|....*....|....*..
gi 809281416 317 AVARLRQADDEDLLMYLLQLVQALKYE 343
Cdd:cd00869   91 AVQWLARLSNDELLDYLPQLVQALKFE 117
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 24-60 4.76e-11

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 60.05  E-value: 4.76e-11
                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 809281416    24 WNEWLKLPVKYPDLPRNAQVALTIWDVYGPGKAVPVG 60
Cdd:smart00142  64 WNEWLTFPIQISDLPREARLCITIYAVKNPSKGSEFG 100
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
 555-699 1.69e-10

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: 63.04  E-value: 1.69e-10
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 555 PAQLFFKTEDGGKYPVIFKHGDDLRQDQLILQIISLMDKLLRKENL----DLKLTPYKVLATSTKHGFMQFIQ-SVPVAE 629
Cdd:cd05170   17 PKKLVFLGSDGKRYPYLFKGLEDLHLDERIMQFLSIVNAMLASDNEhrrrRYRARHYSVTPLGPRSGLIQWVDgATPLFS 96

                         90       100       110       120       130       140       150       160
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 630 VLDT----EGSIQNFFRKYAPSENGP------------------NGISA------------------------------- 656
Cdd:cd05170   97 LYKRwqqrRAAAQAQKNQDSGSTPPPvprpselfynklkpalkaAGIRKstsrrewplevlrqvleelvaetprdllare 176

                        170       180       190       200       210
                 ....*....|....*....|....*....|....*....|....*....|....*.
gi 809281416 657 ------------EVMDTYVKSCAGYCVITYILGVGDRHLDNLLLT-KTGKLFHIDF 699
Cdd:cd05170  177 lwcsspssaewwRVTQRFARSLAVMSMIGYIIGLGDRHLDNILVDlSTGEVVHIDY 232
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
 554-700 2.90e-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: 53.21  E-value: 2.90e-08
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 554 MPAQLFFKTEDGGKYPVIFKHGDDlRQDQLILQIISLMDKLLRKENLDLklTPYKVLATSTKHGF----MQFIQSVPVAE 629
Cdd:cd13968    5 ASAKVFWAEGECTTIGVAVKIGDD-VNNEEGEDLESEMDILRRLKGLEL--NIPKVLVTEDVDGPnillMELVKGGTLIA 81

                         90       100       110       120       130       140       150
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 809281416 630 VLDTEGSiqnffrkyapSENGPNGIsaevmdtyVKSCAGYCVITYILGV--GDRHLDNLLLTKTGKLFHIDFG 700
Cdd:cd13968   82 YTQEEEL----------DEKDVESI--------MYQLAECMRLLHSFHLihRDLNNDNILLSEDGNVKLIDFG 136
PI4Ka cd00871
Phosphoinositide 4-kinase(PI4K), accessory domain (PIK domain); PIK domain is conserved in PI3 ...
 234-360 7.95e-06

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: 46.97  E-value: 7.95e-06
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416 234 NIIVSYP---PTKQLTYEEQDLVWKFRYYLTNQEKALtKFLkcVNWDLPQEAKQALELLGKWKPMDVEDSLELLSSHY-T 309
Cdd:cd00871    7 RLAIHLPsrfPNSKLKSEVTRLVRKHPLAVVKIPEAL-PFL--VTGKSVDENSPDLKYLLYWAPVSPVQALSLFTPQYpG 83

                         90       100       110       120       130
                 ....*....|....*....|....*....|....*....|....*....|.
gi 809281416 310 NPTVRRYAVARLRQADDEDLLMYLLQLVQALKYENFDDIKNGLEPTKKDSQ 360
Cdd:cd00871   84 HPLVLQYAVRVLESYPVETVFFYIPQIVQALRYDKMGYVEEYILETAKRSQ 134
C2_PI3K_class_I_alpha cd08398
C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 24-84 1.99e-05

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: 45.55  E-value: 1.99e-05
                         10        20        30        40        50        60
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 809281416  24 WNEWLKLPVKYPDLPRNAQVALTIWDVYGPGKA----VPVGGTTVSLFGKYGMFRQGMHDLKVWP 84
Cdd:cd08398   57 WNEWLDYDIYIPDLPRSARLCLSICSVKGRKGAkeehCPLAWGNINLFDYTDTLVSGKMALNLWP 121
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 24-97 1.66e-04

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: 43.12  E-value: 1.66e-04
                         10        20        30        40        50        60        70        80
                 ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  24 WNEWLKLPVKYPDLPRNAQVALTiwdVYG-----PGKA-------VPVGGTTVSLFGKYGMFRQGMHDLKVWPNVEADGS 91
Cdd:cd04012   65 WDEWIEFPIPVCQLPRESRLVLT---LYGttsspDGGSnkqrmgpEELGWVSLPLFDFRGVLRQGSLLLGLWPPSKDNPL 141


                 ....*.
gi 809281416  92 EPTKTP 97
Cdd:cd04012  142 GPAPPP 147
PTZ00303 PTZ00303
phosphatidylinositol kinase; Provisional
 534-703 2.01e-04

phosphatidylinositol kinase; Provisional


Pssm-ID: 140324 [Multi-domain]  Cd Length: 1374  Bit Score: 45.08  E-value: 2.01e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  534 PQVKIRGIIPETatLFKSalMPAQLFFktedggkypvIFKHgDDLRQDQLILQIISLMDKLLRKENLDLKLTPYKVLATS 613
Cdd:PTZ00303 1032 PVTAVNGVSPES--LHDS--LPQECMF----------LYKR-ENVERDQLMCISSRLLQMLLSSEIGNAEMLDYSVLPLS 1096

                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 809281416  614 TKHGFMQFIQSVPVAEVLDTEGSIQNFFRKYAPSENgpngisaevmdtYVKSCAGYCVITYILGVGDRHLDNLLLTKTGK 693
Cdd:PTZ00303 1097 CDSGLIEKAEGRELSNLDNMDIASYVLYRGTRSCIN------------FLASAKLFLLLNYIFSIGDRHKGNVLIGTNGA 1164

                         170
                  ....*....|
gi 809281416  694 LFHIDFGYIL 703
Cdd:PTZ00303 1165 LLHIDFRFIF 1174
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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