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Conserved domains on  [gi|2124530590|ref|XP_044631125|]
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phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit gamma isoform X5 [Equus asinus]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 887-1239 0e+00

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: 697.41  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  887 DEFSKEKKLIKILGDIGEKVKSASDPQRQEVLKKEIGRLEEFFQHINTCHLPLNPALCIKGIDRDACSYFRSNALPLKIT 966
Cdd:cd05177      2 KEFSKETKLISILIDAAEKVKTASDTRRKEVLKREASRLEDFFQDVVSCCLPLNPALRVKGIDADACSYFTSNAAPLKIS 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  967 FLNANPMGKNISVIFKAGDDLRQDMLVLQIIQVMDNIWLQEGLDMQMIIYRCLSTGKGQGLVQLVPDAVTLAKIHRRSGL 1046
Cdd:cd05177     82 FINANPLAKNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYRCLSTGKTQGLVQMVPDAVTLAKIHRESGL 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1047 IGPLKENTIKKWFSRHNHLKVDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQTFGGI 1126
Cdd:cd05177    162 IGPLKENTIEKWFHMHNKLKEDYDKAVRNFFHSCAGWCVVTFILGVCDRHNDNIMLTHSGHMFHIDFGKFLGHAQTFGSI 241

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1127 KRDRAPFIFTSEMEYFITEGGKNPQHFQDFVELCCRAYNIVRRHSRLLLNLLEMMLHAGLPELSGIQDLRYVYNNLRPQD 1206
Cdd:cd05177    242 KRDRAPFIFTSEMEYFITEGGKKPQRFQRFVELCCRAYNIVRKHSQLLLNLLEMMLHAGLPELKDIQDLKYVYNNLRPQD 321

                          330       340       350
                   ....*....|....*....|....*....|...
gi 2124530590 1207 TDLEATSHFTKKIKESLECFPVKLNNLIHTLAQ 1239
Cdd:cd05177    322 TDLEATSYFTKKIKESLECFPVKLNNLIHTLAQ 354
PI3Ka super family cl00271
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 712-880 3.80e-76

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.


The actual alignment was detected with superfamily member cd00869:

Pssm-ID: 412275  Cd Length: 169  Bit Score: 249.30  E-value: 3.80e-76
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  712 KECLKHIARLSQKQSPLLLSEEKRRYLWFYRFYCNNENCSLPLVLGSAPGWDERTVSEMHDISRRWKFSHPLEALGLLTS 791
Cdd:cd00869      1 IETQEKLLDLIQKQSTYTLSTEDKDLLWEKRLYCTNEPNALPLVLASAPSWDWANLMDVYQLLHQWAPLRPLIALELLLP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  792 SFPDQEIRKVAVQQLDNLLNDELLEFLPQLVQAVKFEWNLESPLVQLLLHRSLQSIQIAHRLYWLLKDAQNEAYFKSWYQ 871
Cdd:cd00869     81 KFPDQEVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALDDCYFSSAYQ 160


                   ....*....
gi 2124530590  872 KLLAALQFC 880
Cdd:cd00869    161 DLGAALRCQ 169
PX_domain super family cl02563
The Phox Homology domain, a phosphoinositide binding module; The PX domain is a ...
 1268-1361 4.93e-50

The Phox Homology domain, a phosphoinositide binding module; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to membranes. Proteins containing PX domains interact with PIs and have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. Many members of this superfamily bind phosphatidylinositol-3-phosphate (PI3P) but in some cases, other PIs such as PI4P or PI(3,4)P2, among others, are the preferred substrates. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction, as in the cases of p40phox, p47phox, and some sorting nexins (SNXs). The PX domain is conserved from yeast to humans and is found in more than 100 proteins. The majority of PX domain-containing proteins are SNXs, which play important roles in endosomal sorting.


The actual alignment was detected with superfamily member cd06896:

Pssm-ID: 470617  Cd Length: 101  Bit Score: 172.02  E-value: 4.93e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1268 KATILGFSKKTSNLYLIQVTHSNDETSLTEKSFDQFSKLHSQLQKHFASLSLPEFPHWWHLPFTNSDHNRFRDLNRYMEQ 1347
Cdd:cd06896      1 RATILGFSKKSSNLYLVQVTQSCNLVSLTEKSFEQFSELHSQLQKQFPSLALPEFPHWWHLPFTDSDHKRVRDLNHYLEQ 80

                           90
                   ....*....|....
gi 2124530590 1348 ILNGSYEVANNEVV 1361
Cdd:cd06896     81 LLSGSREVANSDCV 94
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 540-695 5.45e-46

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: 163.30  E-value: 5.45e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  540 GLHSHLSFTVYAAHNIPETWVHSYKAFSFSCRLTYAGKKLCQVRNYRNIPVKKLFFFLVNWDETINFPLEIKSLPRESML 619
Cdd:cd04012      5 TVTDLLSVTVSSLHRIPPTWVQSFEDFYLSCSLYHGGRLLCSPVTTKPVKITKSFFPRVVWDEWIEFPIPVCQLPRESRL 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  620 TIKLFGI----IHASN----TANLLAWTCLPLFP-KDKSIPGPVLFSMTSQSEPPIEMIAPgVWDISQPSPVILQIDFPA 690
Cdd:cd04012     85 VLTLYGTtsspDGGSNkqrmGPEELGWVSLPLFDfRGVLRQGSLLLGLWPPSKDNPLGPAP-PPLFEQPDRVILQIDFPS 163


                   ....*
gi 2124530590  691 TKWEY 695
Cdd:cd04012    164 SAFDV 168
PI3K_rbd super family cl02484
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 273-367 1.39e-04

PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding pfam00788 domains (unpublished observation).


The actual alignment was detected with superfamily member pfam00794:

Pssm-ID: 413336  Cd Length: 106  Bit Score: 42.67  E-value: 1.39e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  273 STTTAFPYQLLSNTKFHVNIFTDNSTQVLHFMPYANYLVKDLIAETlhFCKNDQLFPK-----DHLLSVCGYEEFLQNNY 347
Cdd:pfam00794    2 STVSPEPLPKLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQA--LTKKLSVHTQgdvtdDYVLKVCGRDEYLLGDH 79

                           90       100
                   ....*....|....*....|...
gi 2124530590  348 SLGSH---RIFQKDKSVIQLNLQ 367
Cdd:pfam00794   80 PLGQFeyiRNCLKSGREPHLTLV 102
 
Name Accession Description Interval E-value
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 887-1239 0e+00

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: 697.41  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  887 DEFSKEKKLIKILGDIGEKVKSASDPQRQEVLKKEIGRLEEFFQHINTCHLPLNPALCIKGIDRDACSYFRSNALPLKIT 966
Cdd:cd05177      2 KEFSKETKLISILIDAAEKVKTASDTRRKEVLKREASRLEDFFQDVVSCCLPLNPALRVKGIDADACSYFTSNAAPLKIS 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  967 FLNANPMGKNISVIFKAGDDLRQDMLVLQIIQVMDNIWLQEGLDMQMIIYRCLSTGKGQGLVQLVPDAVTLAKIHRRSGL 1046
Cdd:cd05177     82 FINANPLAKNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYRCLSTGKTQGLVQMVPDAVTLAKIHRESGL 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1047 IGPLKENTIKKWFSRHNHLKVDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQTFGGI 1126
Cdd:cd05177    162 IGPLKENTIEKWFHMHNKLKEDYDKAVRNFFHSCAGWCVVTFILGVCDRHNDNIMLTHSGHMFHIDFGKFLGHAQTFGSI 241

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1127 KRDRAPFIFTSEMEYFITEGGKNPQHFQDFVELCCRAYNIVRRHSRLLLNLLEMMLHAGLPELSGIQDLRYVYNNLRPQD 1206
Cdd:cd05177    242 KRDRAPFIFTSEMEYFITEGGKKPQRFQRFVELCCRAYNIVRKHSQLLLNLLEMMLHAGLPELKDIQDLKYVYNNLRPQD 321

                          330       340       350
                   ....*....|....*....|....*....|...
gi 2124530590 1207 TDLEATSHFTKKIKESLECFPVKLNNLIHTLAQ 1239
Cdd:cd05177    322 TDLEATSYFTKKIKESLECFPVKLNNLIHTLAQ 354
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
 712-880 3.80e-76

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: 249.30  E-value: 3.80e-76
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  712 KECLKHIARLSQKQSPLLLSEEKRRYLWFYRFYCNNENCSLPLVLGSAPGWDERTVSEMHDISRRWKFSHPLEALGLLTS 791
Cdd:cd00869      1 IETQEKLLDLIQKQSTYTLSTEDKDLLWEKRLYCTNEPNALPLVLASAPSWDWANLMDVYQLLHQWAPLRPLIALELLLP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  792 SFPDQEIRKVAVQQLDNLLNDELLEFLPQLVQAVKFEWNLESPLVQLLLHRSLQSIQIAHRLYWLLKDAQNEAYFKSWYQ 871
Cdd:cd00869     81 KFPDQEVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALDDCYFSSAYQ 160


                   ....*....
gi 2124530590  872 KLLAALQFC 880
Cdd:cd00869    161 DLGAALRCQ 169
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 979-1193 9.82e-64

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: 216.78  E-value: 9.82e-64
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590   979 VIFKAGDDLRQDMLVLQIIQVMDNIWLQE----GLDMQMIIYRCLSTGKGQGLVQLVPDAVTLAKIHRRS---------- 1044
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  1045 ---------------GLIGPLKENTIKKWFSRHN-HLKVDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHM 1108
Cdd:smart00146   81 rsqtatrlkklelflEATGKFPDPVLYDWFTKKFpDPSEDYFEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  1109 FHIDFGKFLGHAQTFGGIKrDRAPFIFTSEMEYFITEGGknpqHFQDFVELCCRAYNIVRRHSRLLLNLLEMMLHAGLPE 1188
Cdd:smart00146  161 FHIDFGFILGNGPKLFGFP-ERVPFRLTPEMVDVMGDSG----YFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLPD 235


                    ....*
gi 2124530590  1189 LSGIQ 1193
Cdd:smart00146  236 WRSGK 240
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 977-1190 2.15e-52

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: 184.46  E-value: 2.15e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  977 ISVIFKAGDDLRQDMLVLQIIQVMDNIWLQEGLDMQMI-IYRCLSTGKGQGLVQLVPDAVTLAKIHR--RSGLIGPLKEN 1053
Cdd:pfam00454    2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLRRLkPYSVIPLGPKCGIIEWVPNSETLAYILDeyGENGVPPTAMV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1054 TIKKWFSRHNHLKV--------------------------DYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIML-TKSG 1106
Cdd:pfam00454   82 KILHSALNYPKLKLefesrislppkvgllqwfvkkspdaeEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTTG 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1107 HMFHIDFGKFLGHAQTFGGIKrDRAPFIFTSEMEYFITEGGknpqHFQDFVELCCRAYNIVRRHSRLLLNLLEMMLHAGL 1186
Cdd:pfam00454  162 KLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAMGPSG----DEGLFRELCETAYEALRRNLNLLTNLLKLMVADGL 236


                   ....
gi 2124530590 1187 PELS 1190
Cdd:pfam00454  237 PDWS 240
PX_PI3K_C2_gamma cd06896
The phosphoinositide binding Phox Homology Domain of the Gamma Isoform of Class II ...
 1268-1361 4.93e-50

The phosphoinositide binding Phox Homology Domain of the Gamma Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. 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. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. 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 PX domain, and a second C2 domain at the C-terminus. The class II gamma isoform, PI3K-C2gamma, is expressed in the liver, breast, and prostate. It's biological function remains unknown. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


Pssm-ID: 132806  Cd Length: 101  Bit Score: 172.02  E-value: 4.93e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1268 KATILGFSKKTSNLYLIQVTHSNDETSLTEKSFDQFSKLHSQLQKHFASLSLPEFPHWWHLPFTNSDHNRFRDLNRYMEQ 1347
Cdd:cd06896      1 RATILGFSKKSSNLYLVQVTQSCNLVSLTEKSFEQFSELHSQLQKQFPSLALPEFPHWWHLPFTDSDHKRVRDLNHYLEQ 80

                           90
                   ....*....|....
gi 2124530590 1348 ILNGSYEVANNEVV 1361
Cdd:cd06896     81 LLSGSREVANSDCV 94
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 540-695 5.45e-46

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: 163.30  E-value: 5.45e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  540 GLHSHLSFTVYAAHNIPETWVHSYKAFSFSCRLTYAGKKLCQVRNYRNIPVKKLFFFLVNWDETINFPLEIKSLPRESML 619
Cdd:cd04012      5 TVTDLLSVTVSSLHRIPPTWVQSFEDFYLSCSLYHGGRLLCSPVTTKPVKITKSFFPRVVWDEWIEFPIPVCQLPRESRL 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  620 TIKLFGI----IHASN----TANLLAWTCLPLFP-KDKSIPGPVLFSMTSQSEPPIEMIAPgVWDISQPSPVILQIDFPA 690
Cdd:cd04012     85 VLTLYGTtsspDGGSNkqrmGPEELGWVSLPLFDfRGVLRQGSLLLGLWPPSKDNPLGPAP-PPLFEQPDRVILQIDFPS 163


                   ....*
gi 2124530590  691 TKWEY 695
Cdd:cd04012    164 SAFDV 168
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
871-1171 1.01e-31

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 135.68  E-value: 1.01e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  871 QKLLAALQFCAGKALSDEFSKEKKLIKILGDI-GEKVKSASD--PQRQEVLKKEIGRLEEFFQHINTCHLPL-----NPA 942
Cdd:COG5032   1685 SSFLKELIKKSPRKIRKKFKIDISLLNLSRKLyISVLRSIRKrlKRLLELRLKKVSPKLLLFHAFLEIKLPGqylldKPF 1764

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  943 LCIKGIDRDACSYFRSNALPLKITFLNANpmGKNISVIFKAGDDLRQDMLVLQIIQVMDNIWLQEGL----DMQMIIYRC 1018
Cdd:COG5032   1765 VLIERFEPEVSVVKSHLQRPRRLTIRGSD--GKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKV 1842

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1019 LSTGKGQGLVQLVPDAVTLAKIHR---------------------RSGLIGPLK---------ENTIKKWFSRHNHLKVD 1068
Cdd:COG5032   1843 IPLSPGSGIIEWVPNSDTLHSILReyhkrknisidqekklaarldNLKLLLKDEfftkatlksPPVLYDWFSESFPNPED 1922

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1069 YEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTK-SGHMFHIDFGKFLGHAQTFGGIKrDRAPFIFTSEMEYFI---- 1143
Cdd:COG5032   1923 WLTARTNFARSLAVYSVIGYILGLGDRHPGNILIDRsSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAMgvsg 2001

                          330       340
                   ....*....|....*....|....*...
gi 2124530590 1144 TEGGknpqhfqdFVELCCRAYNIVRRHS 1171
Cdd:COG5032   2002 VEGS--------FRELCETAFRALRKNA 2021
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 706-889 4.43e-29

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: 115.05  E-value: 4.43e-29
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590   706 DLEEPPKECLKHIARlsqKQSPLLLSEEKRRYLWFYRFYC--NNENCsLPLVLgSAPGWDERT-VSEMHDISRRWKFSHP 782
Cdd:smart00145    2 PLDIEEREQLEAILK---LDPTYELTEEEKDLIWKFRHYYltNNPKA-LPKFL-LSVKWSDADeVAQALSLLLSWAPLDP 76

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590   783 LEALGLLTSSFPDQEIRKVAVQQLDNLLNDELLEFLPQLVQAVKFEWNLESPLVQLLLHRSLQSIQIAHRLYWLLKDAQN 862
Cdd:smart00145   77 EDALELLDPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELH 156

                           170       180
                    ....*....|....*....|....*..
gi 2124530590   863 EAYFKSWYQKLLAALQFCAGKALSDEF 889
Cdd:smart00145  157 DPHVSIRFGLLLEAYLRGCGTHLKELL 183
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 724-865 3.58e-23

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: 98.17  E-value: 3.58e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  724 KQSPLL-LSEEKRRYLWFYRFYCNNENCSLPLVLGSAPGWDERTVSEMHDISRRWKFSHPLEALGLLTSSFPDQEIRKVA 802
Cdd:pfam00613   18 AYDPLSkLTAEEKDLIWKFRYYLMLVPKALTKLLLSVKWSDLSEVAEALSLLLKWAPIDPVDALELLDPKFPDPEVRQYA 97

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2124530590  803 VQQLDNLLNDELLEFLPQLVQAVKFEWNLESPLVQLLLHRSLQSIQIAHRLYWLLK-DAQNEAY 865
Cdd:pfam00613   98 VKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKsEIHDEEV 161
PX smart00312
PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function ...
 1274-1362 1.40e-14

PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function present in phox proteins, PLD isoforms, a PI3K isoform.


Pssm-ID: 214610  Cd Length: 105  Bit Score: 70.84  E-value: 1.40e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  1274 FSKKTSNLYLIQVTHS-NDETSLTEKSFDQFSKLHSQLQKHFASLSLPEFPHWWHLPFTNSDHNRF-----RDLNRYMEQ 1347
Cdd:smart00312    7 IGDGKHYYYVIEIETKtGLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRLNNFSEEFiekrrRGLEKYLQS 86

                            90
                    ....*....|....*
gi 2124530590  1348 ILNGSYEVANNEVVK 1362
Cdd:smart00312   87 LLNHPELINHSEVVL 101
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 543-627 6.94e-12

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 63.13  E-value: 6.94e-12
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590   543 SHLSFTVYAAHNIPETWVHSYKAFSFSCRLTYAGKKLCQVRNYRNIPvkklFFFLVNWDETINFPLEIKSLPRESMLTIK 622
Cdd:smart00142   11 RNLVITIALIHGIPLNWSRDYSDLYVEIQLYHGGKLLCLPVSTSYKP----FFPSVKWNEWLTFPIQISDLPREARLCIT 86


                    ....*
gi 2124530590   623 LFGII 627
Cdd:smart00142   87 IYAVK 91
PX pfam00787
PX domain; PX domains bind to phosphoinositides.
 1286-1362 1.35e-10

PX domain; PX domains bind to phosphoinositides.


Pssm-ID: 459940  Cd Length: 84  Bit Score: 58.79  E-value: 1.35e-10
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2124530590 1286 VTHSNDETSLTEKSFDQFSKLHSQLQKHFASLSLPEFPHW-WHLPFTNSD-HNRFRDLNRYMEQILNGSyEVANNEVVK 1362
Cdd:pfam00787    1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSVIIPPLPPKrWLGRYNEEFiEKRRKGLEQYLQRLLQHP-ELRNSEVLL 78
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 569-648 1.90e-09

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: 57.38  E-value: 1.90e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  569 SCRLTYAGKKLCQVRNYRNIPVKKLFFflvNWDETINFPLEIKSLPRESMLTIKLFGIIHASNTANLLAWTCLPLFPKDK 648
Cdd:pfam00792    8 ECQLYHGGKPLCLPVSTRYVPFSNSSI---KWNEWITFPIQISDLPRSARLCITIWDVSGPEKSFVPIGWVNTSLFDKKG 84
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 273-367 1.39e-04

PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding pfam00788 domains (unpublished observation).


Pssm-ID: 395642  Cd Length: 106  Bit Score: 42.67  E-value: 1.39e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  273 STTTAFPYQLLSNTKFHVNIFTDNSTQVLHFMPYANYLVKDLIAETlhFCKNDQLFPK-----DHLLSVCGYEEFLQNNY 347
Cdd:pfam00794    2 STVSPEPLPKLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQA--LTKKLSVHTQgdvtdDYVLKVCGRDEYLLGDH 79

                           90       100
                   ....*....|....*....|...
gi 2124530590  348 SLGSH---RIFQKDKSVIQLNLQ 367
Cdd:pfam00794   80 PLGQFeyiRNCLKSGREPHLTLV 102
 
Name Accession Description Interval E-value
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 887-1239 0e+00

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: 697.41  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  887 DEFSKEKKLIKILGDIGEKVKSASDPQRQEVLKKEIGRLEEFFQHINTCHLPLNPALCIKGIDRDACSYFRSNALPLKIT 966
Cdd:cd05177      2 KEFSKETKLISILIDAAEKVKTASDTRRKEVLKREASRLEDFFQDVVSCCLPLNPALRVKGIDADACSYFTSNAAPLKIS 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  967 FLNANPMGKNISVIFKAGDDLRQDMLVLQIIQVMDNIWLQEGLDMQMIIYRCLSTGKGQGLVQLVPDAVTLAKIHRRSGL 1046
Cdd:cd05177     82 FINANPLAKNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYRCLSTGKTQGLVQMVPDAVTLAKIHRESGL 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1047 IGPLKENTIKKWFSRHNHLKVDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQTFGGI 1126
Cdd:cd05177    162 IGPLKENTIEKWFHMHNKLKEDYDKAVRNFFHSCAGWCVVTFILGVCDRHNDNIMLTHSGHMFHIDFGKFLGHAQTFGSI 241

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1127 KRDRAPFIFTSEMEYFITEGGKNPQHFQDFVELCCRAYNIVRRHSRLLLNLLEMMLHAGLPELSGIQDLRYVYNNLRPQD 1206
Cdd:cd05177    242 KRDRAPFIFTSEMEYFITEGGKKPQRFQRFVELCCRAYNIVRKHSQLLLNLLEMMLHAGLPELKDIQDLKYVYNNLRPQD 321

                          330       340       350
                   ....*....|....*....|....*....|...
gi 2124530590 1207 TDLEATSHFTKKIKESLECFPVKLNNLIHTLAQ 1239
Cdd:cd05177    322 TDLEATSYFTKKIKESLECFPVKLNNLIHTLAQ 354
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 888-1239 0e+00

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: 551.51  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  888 EFSKEKKLIKILGDIGEKVKSASDPQRQEVLKKEIGRLEEFFQHiNTCHLPLNPALCIKGIDRDACSYFRSNALPLKITF 967
Cdd:cd05166      3 EFLKQHVLVQALTSIAEKVKSAKDSARENALRRELEQLASFLLE-NSFRLPLDPALEVTGVDVRSCSYFNSNALPLKLVF 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  968 LNANPMGKNISVIFKAGDDLRQDMLVLQIIQVMDNIWLQEGLDMQMIIYRCLSTGKGQGLVQLVPDAVTLAKIHRRSGLI 1047
Cdd:cd05166     82 RNADPRAEPISVIFKVGDDLRQDMLTLQLIRIMDKIWLQEGLDLKMITFRCVPTGNKRGMVELVPEAETLREIQTEHGLT 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1048 GPLKENTIKKWFSRHNHLKVDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQTFGGIK 1127
Cdd:cd05166    162 GSFKDRPLADWLQKHNPSELEYEKAVENFIRSCAGYCVATYVLGICDRHNDNIMLKTSGHLFHIDFGKFLGDAQMFGNFK 241

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1128 RDRAPFIFTSEMEYFITEGGKNPQHFQDFVELCCRAYNIVRRHSRLLLNLLEMMLHAGLPELSgIQDLRYVYNNLRPQDT 1207
Cdd:cd05166    242 RDRVPFVLTSDMAYVINGGDKPSSRFQLFVDLCCQAFNIIRKNSNLLLNLLSLMLSSGIPGVT-QDDLRYVQDALLPELT 320

                          330       340       350
                   ....*....|....*....|....*....|..
gi 2124530590 1208 DLEATSHFTKKIKESLECFPVKLNNLIHTLAQ 1239
Cdd:cd05166    321 DAEATAHFTRMIEESLSSKFTQLNFFIHNLAQ 352
PI3Kc_C2_alpha cd05176
Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 887-1239 1.91e-144

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: 443.65  E-value: 1.91e-144
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  887 DEFSKEKKLIKILGDIGEKVKSASDPQRQEVLKKEIGRLEEFFQHiNTCHLPLNPALCIKGIDRDACSYFRSNALPLKIT 966
Cdd:cd05176      2 EELEKQTRLVQLLGRVAEKVRQASGSARQVALQDGMERVQSFFQK-NKCRLPLSPSLVAKELNIKACSFFSSNAVPLKVA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  967 FLNANPMGKNISVIFKAGDDLRQDMLVLQIIQVMDNIWLQEGLDMQMIIYRCLSTGKGQGLVQLVPDAVTLAKIHRRSGL 1046
Cdd:cd05176     81 LVNADPLGEEINVMFKVGEDLRQDMLALQMIKIMDKIWLQEGLDLRMVIFKCLSTGKDRGMVELVPSSDTLRKIQVEYGV 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1047 IGPLKENTIKKWFSRHNHLKVDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQTFGGI 1126
Cdd:cd05176    161 TGSFKDKPLAEWLRKYNPSEEEYEKASENFIYSCAGCCVATYVLGICDRHNDNIMLRSTGHMFHIDFGKFLGHAQMFGSF 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1127 KRDRAPFIFTSEMEYFITEGGKNPQHFQDFVELCCRAYNIVRRHSRLLLNLLEMMLHAGLPELSGIQDLRYVYNNLRPQD 1206
Cdd:cd05176    241 KRDRAPFVLTSDMAYVINGGEKPTIRFQLFVDLCCQAYNLIRKHTNLFLNLLSLMLSSGLPELTGIQDLKYVFDALQPQT 320

                          330       340       350
                   ....*....|....*....|....*....|...
gi 2124530590 1207 TDLEATSHFTKKIKESLECFPVKLNNLIHTLAQ 1239
Cdd:cd05176    321 TDAEATIFFTRLIESSLGSVATKFNFFIHNLAQ 353
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 888-1223 1.56e-142

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: 437.77  E-value: 1.56e-142
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  888 EFSKEKKLIKILGDIGEKVKSASDPQRQEVLKKEIGRLEEFfqhiNTCHLPLNPALCIKGIDRDACSYFRSNALPLKITF 967
Cdd:cd00891      3 ELLKQVKVLDELKEIAKKIKEEPSEERKEVLEKLLQKLELP----KKFTLPLDPRMEVKGLIVEKCKVMDSKKLPLWLVF 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  968 LNANPMGKNISVIFKAGDDLRQDMLVLQIIQVMDNIWLQEGLDMQMIIYRCLSTGKGQGLVQLVPDAVTLAKIHRRSG-L 1046
Cdd:cd00891     79 KNADPGGDPIKVIFKAGDDLRQDQLTLQLLRIMDKLWKKEGLDLRMTPYKCIATGDEVGMIEVVPNSETTAAIQKKYGgF 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1047 IGPLKENTIKKWFSRHNHLKVDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQTFGGI 1126
Cdd:cd00891    159 GAAFKDTPISNWLKKHNPTEEEYEEAVENFIRSCAGYCVATYVLGIGDRHNDNIMVTKSGHLFHIDFGHFLGNFKKKFGI 238

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1127 KRDRAPFIFTSEMEYFIteGGKNPQHFQDFVELCCRAYNIVRRHSRLLLNLLEMMLHAGLPELSGIQDLRYVYNNLRPQD 1206
Cdd:cd00891    239 KRERAPFVFTPEMAYVM--GGEDSENFQKFEDLCCKAYNILRKHGNLLINLFSLMLSAGIPELQSIEDIEYLRDALQLDL 316

                          330
                   ....*....|....*..
gi 2124530590 1207 TDLEATSHFTKKIKESL 1223
Cdd:cd00891    317 SDEEAAEHFRKLIHESL 333
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 887-1239 2.79e-137

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: 424.41  E-value: 2.79e-137
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  887 DEFSKEKKLIKILGDIGEKVKSASDPQRQEVLKKEIGRLEEFFQHINTCHLPLNPALCIKGIDRDACSYFRSNALPLKIT 966
Cdd:cd00895      2 EEFDRQCWLVNVLAKLAQQVREAAPSARQGILREGLEEVKQFFSINGSCRLPLSPSLLVKGIVPRDCSYFNSNAVPLKLS 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  967 FLNANPMGKNISVIFKAGDDLRQDMLVLQIIQVMDNIWLQEGLDMQMIIYRCLSTGKGQGLVQLVPDAVTLAKIHRRSGL 1046
Cdd:cd00895     82 FQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMNKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEHGV 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1047 IGPLKENTIKKWFSRHNHLKVDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQTFGGI 1126
Cdd:cd00895    162 TGSFKDRPLADWLQKHNPTEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGNI 241

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1127 KRDRAPFIFTSEMEYFITEGGKNPQHFQDFVELCCRAYNIVRRHSRLLLNLLEMMLHAGLPELSGIQDLRYVYNNLRPQD 1206
Cdd:cd00895    242 KRDRAPFVFTSDMAYVINGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQD 321

                          330       340       350
                   ....*....|....*....|....*....|...
gi 2124530590 1207 TDLEATSHFTKKIKESLECFPVKLNNLIHTLAQ 1239
Cdd:cd00895    322 TEADATTYFTRLIESSLGSVATKLNFFIHNLAQ 354
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 894-1239 2.65e-106

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: 341.54  E-value: 2.65e-106
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  894 KLIKILGDIGEKVKSAsdpqRQEVLKKEigRLEEFFQHIntcHLPLNPALCIKGIDRDACSYFRSNALPLKITFLNANPM 973
Cdd:cd05165     19 DILKEKKKSKEKVKKL----LKECLKQK--FYDEALQNF---QSPLNPSHKLGELIIEKCKVMDSKKRPLWLVFENADPL 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  974 ---GKNISVIFKAGDDLRQDMLVLQIIQVMDNIWLQEGLDMQMIIYRCLSTGKGQGLVQLVPDAVTLAKIHRRSGL--IG 1048
Cdd:cd05165     90 alsGEDIKIIFKNGDDLRQDMLTLQIIRIMDNIWKEEGLDLRMLPYGCLSTGDNVGLIEVVRNAKTIANIQKKKGKvaTL 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1049 PLKENTIKKWFSRHNHLKVDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQTFGGIKR 1128
Cdd:cd05165    170 AFNKDSLHKWLKEKNKTGEKYDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVKENGQLFHIDFGHFLGNFKKKFGIKR 249

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1129 DRAPFIFTSEMEYFITEGGK--NPQHFQDFVELCCRAYNIVRRHSRLLLNLLEMMLHAGLPELSGIQDLRYVYNNLRPQD 1206
Cdd:cd05165    250 ERVPFVLTHDFVYVIARGQDntKSEEFQEFQELCEKAYLILRRHGNLFISLFSMMLSTGIPELTSVKDIEYLRKTLALDK 329

                          330       340       350
                   ....*....|....*....|....*....|....
gi 2124530590 1207 TDLEATSHFTKKIKESL-ECFPVKLNNLIHTLAQ 1239
Cdd:cd05165    330 TEEEALKYFRKKFNEALkGSWTTKVNWFFHNVKH 363
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 890-1239 2.95e-81

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: 270.94  E-value: 2.95e-81
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  890 SKEKKLIKILGDIGEKVKSASD--PQRQEVLKKEIGRLEEFFQHINT-CHLPLNPALCIKGIDRDACSYFRSNALPLKIT 966
Cdd:cd00896      5 KRQQEFVDRLRSLMKEVKNEKGsrDKKIERLRELLSDSELGLLLFFEpLPLPLDPSVKVTGIIPEKSTVFKSALMPLKLT 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  967 FLNANpmGKNISVIFKAGDDLRQDMLVLQIIQVMDNIWLQEGLDMQMIIYRCLSTGKGQGLVQLVPDAVTLAKIHRrsgl 1046
Cdd:cd00896     85 FKTLD--GGEYKVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVPNSKALADILK---- 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1047 igplKENTIKKWFsRHNHLKVDYEK-----ALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGhaq 1121
Cdd:cd00896    159 ----KYGSILNFL-RKHNPDESGPYgikpeVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHIDFGYILG--- 230

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1122 tfggikRD----RAPFIFTSEMeyfiTE--GGKNPQHFQDFVELCCRAYNIVRRHSRLLLNLLEMMLHAGLPELSGIQD- 1194
Cdd:cd00896    231 ------RDpkpfPPPMKLCKEM----VEamGGANSEGYKEFKKYCCTAYNILRKHANLILNLFSLMVDANIPDIALEPDk 300

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*..
gi 2124530590 1195 -LRYVYNNLRPQDTDLEATSHFTKKIKESL-ECFPVkLNNLIHTLAQ 1239
Cdd:cd00896    301 aVLKVQEKFRLDLSDEEAEQYFQNLIDESVnALFPA-VVETIHKIAQ 346
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 891-1239 7.27e-79

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: 264.99  E-value: 7.27e-79
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  891 KEKKLIKILGDIGEKVKSASD----PQRQEVLKKEIgRLEEFFQHINTCHLPLNPALCIKGIDRDACSYFRSNALPLKIT 966
Cdd:cd05174      9 KQGEALSKMKALNDFVKVSSQkatkPQTKEMMHVCM-KQETYMEALSHLQSPLDPSIILEEVCVDQCTFMDSKMKPLWIM 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  967 FLNANPMGKNISVIFKAGDDLRQDMLVLQIIQVMDNIWLQEGLDMQMIIYRCLSTGKGQGLVQLVPDAVTLAKIHR---R 1043
Cdd:cd05174     88 YSSEEAGAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTIANIQLnksN 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1044 SGLIGPLKENTIKKWFSRHNHLKVdYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQTF 1123
Cdd:cd05174    168 MAATAAFNKDALLNWLKSKNPGDA-LDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKTK 246

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1124 GGIKRDRAPFIFTSEMEYFITEG-GKNPQHFQDFVELCCRAYNIVRRHSRLLLNLLEMMLHAGLPELSGIQDLRYVYNNL 1202
Cdd:cd05174    247 FGINRERVPFILTYDFVHVIQQGkTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCSKDIQYLKDSL 326

                          330       340       350
                   ....*....|....*....|....*....|....*...
gi 2124530590 1203 RPQDTDLEATSHFTKKIKESL-ECFPVKLNNLIHTLAQ 1239
Cdd:cd05174    327 ALGKTEEEALKHFRVKFNEALrESWKTKVNWLAHNVSK 364
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
 712-880 3.80e-76

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: 249.30  E-value: 3.80e-76
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  712 KECLKHIARLSQKQSPLLLSEEKRRYLWFYRFYCNNENCSLPLVLGSAPGWDERTVSEMHDISRRWKFSHPLEALGLLTS 791
Cdd:cd00869      1 IETQEKLLDLIQKQSTYTLSTEDKDLLWEKRLYCTNEPNALPLVLASAPSWDWANLMDVYQLLHQWAPLRPLIALELLLP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  792 SFPDQEIRKVAVQQLDNLLNDELLEFLPQLVQAVKFEWNLESPLVQLLLHRSLQSIQIAHRLYWLLKDAQNEAYFKSWYQ 871
Cdd:cd00869     81 KFPDQEVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALDDCYFSSAYQ 160


                   ....*....
gi 2124530590  872 KLLAALQFC 880
Cdd:cd00869    161 DLGAALRCQ 169
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 936-1239 4.21e-72

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: 245.64  E-value: 4.21e-72
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  936 HLPLNPALCIKGIDRDACSYFRSNALPLKITFLNANPMGKNISVIFKAGDDLRQDMLVLQIIQVMDNIWLQEGLDMQMII 1015
Cdd:cd05173     54 QSPLNPSIILSELNVEKCKYMDSKMKPLWIVYNNKLFGGDSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVP 133

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1016 YRCLSTGKGQGLVQLVPDAVTLAKIHRRSGLI---GPLKENTIKKWFSRHNhLKVDYEKALRNFFYSCAGWCVVTFILGV 1092
Cdd:cd05173    134 YGCLATGDRSGLIEVVSSAETIADIQLNSSNVaaaAAFNKDALLNWLKEYN-SGDDLERAIEEFTLSCAGYCVATYVLGI 212

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1093 CDRHNDNIMLTKSGHMFHIDFGKFLGHAQTFGGIKRDRAPFIFTSEMEYFITEGGK-NPQHFQDFVELCCRAYNIVRRHS 1171
Cdd:cd05173    213 GDRHSDNIMVRKNGQLFHIDFGHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTgNTEKFGRFRQYCEDAYLILRKNG 292

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2124530590 1172 RLLLNLLEMMLHAGLPELSGIQDLRYVYNNLRPQDTDLEATSHFTKKIKESL-ECFPVKLNNLIHTLAQ 1239
Cdd:cd05173    293 NLFITLFALMLTAGLPELTSVKDIQYLKDSLALGKSEEEALKQFRQKFDEALrESWTTKVNWMAHTVRK 361
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 887-1220 6.46e-72

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: 245.16  E-value: 6.46e-72
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  887 DEFSKEKKLIKILGDIGEKVKSASDPQ-----------RQEVLKKEIGRLEEFFQhintchLPLNPALCIKGIDRDACSY 955
Cdd:cd00894      2 HDFTQQVQVIEMLQKVTLDIKSLSAEKydvssqvisqlKQKLENLQNSQLPESFR------VPYDPGLRAGALVIEKCKV 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  956 FRSNALPLKITFLNANPMG---KNISVIFKAGDDLRQDMLVLQIIQVMDNIWLQEGLDMQMIIYRCLSTGKGQGLVQLVP 1032
Cdd:cd00894     76 MASKKKPLWLEFKCADPTAlsnETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVK 155

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1033 DAVTLAKIHRRS-GLIGPLKENTIKKWFSRHNHLKVDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHI 1111
Cdd:cd00894    156 DATTIAKIQQSTvGNTGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHI 235

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1112 DFGKFLGHAQTFGGIKRDRAPFIFTSEMEYFI-TEGGKNPQHFQDFVELCCRAYNIVRRHSRLLLNLLEMMLHAGLPELS 1190
Cdd:cd00894    236 DFGHILGNYKSFLGINKERVPFVLTPDFLFVMgTSGKKTSLHFQKFQDVCVKAYLALRHHTNLLIILFSMMLMTGMPQLT 315

                          330       340       350
                   ....*....|....*....|....*....|
gi 2124530590 1191 GIQDLRYVYNNLRPQDTDLEATSHFTKKIK 1220
Cdd:cd00894    316 SKEDIEYIRDALTVGKSEEDAKKHFLDQIE 345
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 979-1193 9.82e-64

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: 216.78  E-value: 9.82e-64
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590   979 VIFKAGDDLRQDMLVLQIIQVMDNIWLQE----GLDMQMIIYRCLSTGKGQGLVQLVPDAVTLAKIHRRS---------- 1044
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  1045 ---------------GLIGPLKENTIKKWFSRHN-HLKVDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHM 1108
Cdd:smart00146   81 rsqtatrlkklelflEATGKFPDPVLYDWFTKKFpDPSEDYFEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  1109 FHIDFGKFLGHAQTFGGIKrDRAPFIFTSEMEYFITEGGknpqHFQDFVELCCRAYNIVRRHSRLLLNLLEMMLHAGLPE 1188
Cdd:smart00146  161 FHIDFGFILGNGPKLFGFP-ERVPFRLTPEMVDVMGDSG----YFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLPD 235


                    ....*
gi 2124530590  1189 LSGIQ 1193
Cdd:smart00146  236 WRSGK 240
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 883-1239 2.39e-63

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: 220.70  E-value: 2.39e-63
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  883 KALSDEFSKEKKLIKILGDIGEKVKSASDPQRQEVLKKEIgRLEEFFQHINTCHLPLNPALCIKGIDRDACSYFRSNALP 962
Cdd:cd05175      6 KHLSRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQM-RRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKRP 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  963 LKITFLNANPMG----KNISVIFKAGDDLRQDMLVLQIIQVMDNIWLQEGLDMQMIIYRCLSTGKGQGLVQLVPDAVTLA 1038
Cdd:cd05175     85 LWLNWENPDIMSellfQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHTIM 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1039 KIHRRSGLIGPLKEN--TIKKWFSRHNHLKVdYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKF 1116
Cdd:cd05175    165 QIQCKGGLKGALQFNshTLHQWLKDKNKGEI-YDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGHF 243

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1117 LGHAQTFGGIKRDRAPFIFTSEMEYFITEGGK---NPQHFQDFVELCCRAYNIVRRHSRLLLNLLEMMLHAGLPELSGIQ 1193
Cdd:cd05175    244 LDHKKKKFGYKRERVPFVLTQDFLIVISKGAQectKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSFD 323

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*..
gi 2124530590 1194 DLRYVYNNLRPQDTDLEATSHFTKKIKESLE-CFPVKLNNLIHTLAQ 1239
Cdd:cd05175    324 DIAYIRKTLALDKTEQEALEYFMKQMNDAHHgGWTTKMDWIFHTIKQ 370
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
 975-1224 3.71e-56

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: 3.71e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  975 KNISVIFKAGDDLRQDMLVLQIIQVMDNIWLQEGLDMQMIIYRCLSTGKGQGLVQLVPDAVTLAKIHRrsgligpLKENT 1054
Cdd:cd05167     48 VWQAAIFKVGDDCRQDMLALQLISLFKNIFEEVGLDLYLFPYRVVATGPGCGVIEVIPNSKSRDQIGR-------ETDNG 120

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1055 IKKWFSRH--NHLKVDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGkFLGHAQTFGGIKRDRAP 1132
Cdd:cd05167    121 LYEYFLSKygDESTPAFQKARRNFIKSMAGYSLVSYLLQIKDRHNGNIMIDDDGHIIHIDFG-FIFEISPGGNLGFESAP 199

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1133 FIFTSEMEYFItEGGKNPQHFQDFVELCCRAYNIVRRHSRLLLNLLEMMLHAGLPELSG--IQDLRyvyNNLRPQDTDLE 1210
Cdd:cd05167    200 FKLTKEMVDLM-GGSMESEPFKWFVELCVRGYLAVRPYAEAIVSLVELMLDSGLPCFRGqtIKNLR---ERFALEMSERE 275

                          250
                   ....*....|....
gi 2124530590 1211 ATSHFTKKIKESLE 1224
Cdd:cd05167    276 AANFMIKLIADSYL 289
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
 975-1223 1.41e-52

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: 186.31  E-value: 1.41e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  975 KNISVIFKAGDDLRQDMLVLQIIQVMDNIWLQEGLDMQMIIYRCLSTGKGQGLVQLVPDAVTLAKIHRRSGLIGplKENT 1054
Cdd:cd00893     26 KLVSLIVKTGDDLKQEQLALQLISQFDQIFKEEGLPLWLRPYEILSLGPDSGIIEMIKNAVSIDSLKKKLDSFN--KFVS 103

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1055 IKKWFsRHNHLKVDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQtfGGIKRDRAPFI 1134
Cdd:cd00893    104 LSDFF-DDNFGDEAIQKARDNFLQSLVAYSLVCYFLQIKDRHNGNILLDKEGHIIHIDFGFFLSSHP--GFYGFEGAPFK 180

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1135 FTSemEYFITEGGKNPQHFQDFVELCCRAYNIVRRHSRLLLNLLEMMLHAGLPELSGIQDLRYVYNNLRPQDTDLEATSH 1214
Cdd:cd00893    181 LSS--EYIEVLGGVDSELFKEFRKLFLKGFMALRKHSDKILSLVEMMYSGHGITCFGKKTIQQLKQRFNPELTEGELEVY 258


                   ....*....
gi 2124530590 1215 FTKKIKESL 1223
Cdd:cd00893    259 VLSLINKSL 267
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 977-1190 2.15e-52

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: 184.46  E-value: 2.15e-52
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  977 ISVIFKAGDDLRQDMLVLQIIQVMDNIWLQEGLDMQMI-IYRCLSTGKGQGLVQLVPDAVTLAKIHR--RSGLIGPLKEN 1053
Cdd:pfam00454    2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLRRLkPYSVIPLGPKCGIIEWVPNSETLAYILDeyGENGVPPTAMV 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1054 TIKKWFSRHNHLKV--------------------------DYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIML-TKSG 1106
Cdd:pfam00454   82 KILHSALNYPKLKLefesrislppkvgllqwfvkkspdaeEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTTG 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1107 HMFHIDFGKFLGHAQTFGGIKrDRAPFIFTSEMEYFITEGGknpqHFQDFVELCCRAYNIVRRHSRLLLNLLEMMLHAGL 1186
Cdd:pfam00454  162 KLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAMGPSG----DEGLFRELCETAYEALRRNLNLLTNLLKLMVADGL 236


                   ....
gi 2124530590 1187 PELS 1190
Cdd:pfam00454  237 PDWS 240
PX_PI3K_C2_gamma cd06896
The phosphoinositide binding Phox Homology Domain of the Gamma Isoform of Class II ...
 1268-1361 4.93e-50

The phosphoinositide binding Phox Homology Domain of the Gamma Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. 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. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. 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 PX domain, and a second C2 domain at the C-terminus. The class II gamma isoform, PI3K-C2gamma, is expressed in the liver, breast, and prostate. It's biological function remains unknown. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


Pssm-ID: 132806  Cd Length: 101  Bit Score: 172.02  E-value: 4.93e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1268 KATILGFSKKTSNLYLIQVTHSNDETSLTEKSFDQFSKLHSQLQKHFASLSLPEFPHWWHLPFTNSDHNRFRDLNRYMEQ 1347
Cdd:cd06896      1 RATILGFSKKSSNLYLVQVTQSCNLVSLTEKSFEQFSELHSQLQKQFPSLALPEFPHWWHLPFTDSDHKRVRDLNHYLEQ 80

                           90
                   ....*....|....
gi 2124530590 1348 ILNGSYEVANNEVV 1361
Cdd:cd06896     81 LLSGSREVANSDCV 94
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 540-695 5.45e-46

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: 163.30  E-value: 5.45e-46
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  540 GLHSHLSFTVYAAHNIPETWVHSYKAFSFSCRLTYAGKKLCQVRNYRNIPVKKLFFFLVNWDETINFPLEIKSLPRESML 619
Cdd:cd04012      5 TVTDLLSVTVSSLHRIPPTWVQSFEDFYLSCSLYHGGRLLCSPVTTKPVKITKSFFPRVVWDEWIEFPIPVCQLPRESRL 84

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  620 TIKLFGI----IHASN----TANLLAWTCLPLFP-KDKSIPGPVLFSMTSQSEPPIEMIAPgVWDISQPSPVILQIDFPA 690
Cdd:cd04012     85 VLTLYGTtsspDGGSNkqrmGPEELGWVSLPLFDfRGVLRQGSLLLGLWPPSKDNPLGPAP-PPLFEQPDRVILQIDFPS 163


                   ....*
gi 2124530590  691 TKWEY 695
Cdd:cd04012    164 SAFDV 168
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
 977-1170 1.05e-45

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


Pssm-ID: 270712 [Multi-domain]  Cd Length: 292  Bit Score: 166.89  E-value: 1.05e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  977 ISVIFKAGDDLRQDMLVLQIIQVMDNIWLQEGLDMQMIIYRCLSTGKGQGLVQLVPDAVTLAKIHRRSGLIGPLKENTIK 1056
Cdd:cd05168     31 RSVIVKSGDDLRQELLAMQLIKQFQRIFEEAGLPLWLRPYEILVTSSDSGLIETIPDTVSIDSLKKRFPNFTSLLDYFER 110

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1057 KWFSRHNHlkvDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQtfGGIKRDRAPFIFT 1136
Cdd:cd05168    111 TFGDPNSE---RFKEAQRNFVESLAAYSLVCYLLQIKDRHNGNILLDSEGHIIHIDFGFMLSNSP--GGLGFETAPFKLT 185

                          170       180       190
                   ....*....|....*....|....*....|....
gi 2124530590 1137 SEMEYFIteGGKNPQHFQDFVELCCRAYNIVRRH 1170
Cdd:cd05168    186 QEYVEVM--GGLESDMFRYFKTLMIQGFLALRKH 217
PI3Ka cd00864
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 712-858 6.17e-42

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: 150.83  E-value: 6.17e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  712 KECLKHIARLSQKQSPLLLSEEKRRYLWFYRFYCNNENCSLPLVLGSAPGWDERTVSEMHDISRRWKFSHPLEALGLLTS 791
Cdd:cd00864      1 AWERKPLLAILLYPPFSTLTEEEKELLWKFRYYLLNVPKALPKLLKSVNWNDDEEVSELYQLLKWWAPLSPEDALELLSP 80

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2124530590  792 SFPDQEIRKVAVQQLDNLLNDELLEFLPQLVQAVKFEWNLESPLVQLLLHRSLQSIQIAHRLYWLLK 858
Cdd:cd00864     81 KYPDPVVRQYAVRVLESASDDELLLYLPQLVQALKYEPYLDSYLARFLLERALKSQRLGHQLYWNLK 147
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
 948-1171 3.50e-34

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: 130.92  E-value: 3.50e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  948 IDRDACSYFRSNALPLKITFLNANpmGKNISVIFKAGDDLRQDMLVLQIIQVMDNIWLQEGLDMQMIIYRCLSTGKGQGL 1027
Cdd:cd00142      3 LDVGILKVIHSKQRPKKITLIGAD--GKTYSFLLKRRDDLRKDERSFQFMRLIQSILEKESVNLVLPPYKVIPLSENSGL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1028 VQLVPDAVTLAkihrrsgligplkenTIKKWFSRHNhlkVDYEKAL---RNFFYSCAGWCVVTFILGVCDRHNDNIMLTK 1104
Cdd:cd00142     81 IEIVKDAQTIE---------------DLLKSLWRKS---PSSQSWLnrrENFSCSLAGYSVLGYIFGIGDRHPSNIMIEP 142

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 2124530590 1105 SGHMFHIDFGKFLGHAQTFggIKRDRAPFIFTSEMEYFITEGGknpqHFQDFVELCCRAYNIVRRHS 1171
Cdd:cd00142    143 SGNIFHIDFGFIFSGRKLA--EGVETVPFRLTPMLENAMGTAG----VNGPFQISMVKIMEILREHA 203
PX_PI3K_C2 cd06883
The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases; The ...
 1269-1361 7.26e-32

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. 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 are also involved in the regulation of clathrin-mediated membrane trafficking as well as ATP-dependent priming of neurosecretory granule exocytosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. 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 PX domain, and a second C2 domain at the C-terminus. Class II PI3Ks include three vertebrate isoforms (alpha, beta, and gamma), the Drosophila PI3K_68D, and similar proteins.


Pssm-ID: 132793  Cd Length: 109  Bit Score: 120.54  E-value: 7.26e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1269 ATILGFSKKTS----NLYLIQVTHSN-DETSLTEKSFDQFSKLHSQLQKHFASLSLPEFPHWWHLPFTN---SDHNRFRD 1340
Cdd:cd06883      2 VSVFGFQKRYSpekyYIYVVKVTRENqTEPSFVFRTFEEFQELHNKLSLLFPSLKLPSFPARVVLGRSHikqVAERRKIE 81

                           90       100
                   ....*....|....*....|.
gi 2124530590 1341 LNRYMEQILNGSYEVANNEVV 1361
Cdd:cd06883     82 LNSYLKSLFNASPEVAESDLV 102
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
871-1171 1.01e-31

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 135.68  E-value: 1.01e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  871 QKLLAALQFCAGKALSDEFSKEKKLIKILGDI-GEKVKSASD--PQRQEVLKKEIGRLEEFFQHINTCHLPL-----NPA 942
Cdd:COG5032   1685 SSFLKELIKKSPRKIRKKFKIDISLLNLSRKLyISVLRSIRKrlKRLLELRLKKVSPKLLLFHAFLEIKLPGqylldKPF 1764

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  943 LCIKGIDRDACSYFRSNALPLKITFLNANpmGKNISVIFKAGDDLRQDMLVLQIIQVMDNIWLQEGL----DMQMIIYRC 1018
Cdd:COG5032   1765 VLIERFEPEVSVVKSHLQRPRRLTIRGSD--GKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKV 1842

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1019 LSTGKGQGLVQLVPDAVTLAKIHR---------------------RSGLIGPLK---------ENTIKKWFSRHNHLKVD 1068
Cdd:COG5032   1843 IPLSPGSGIIEWVPNSDTLHSILReyhkrknisidqekklaarldNLKLLLKDEfftkatlksPPVLYDWFSESFPNPED 1922

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1069 YEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTK-SGHMFHIDFGKFLGHAQTFGGIKrDRAPFIFTSEMEYFI---- 1143
Cdd:COG5032   1923 WLTARTNFARSLAVYSVIGYILGLGDRHPGNILIDRsSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAMgvsg 2001

                          330       340
                   ....*....|....*....|....*...
gi 2124530590 1144 TEGGknpqhfqdFVELCCRAYNIVRRHS 1171
Cdd:COG5032   2002 VEGS--------FRELCETAFRALRKNA 2021
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 706-889 4.43e-29

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: 115.05  E-value: 4.43e-29
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590   706 DLEEPPKECLKHIARlsqKQSPLLLSEEKRRYLWFYRFYC--NNENCsLPLVLgSAPGWDERT-VSEMHDISRRWKFSHP 782
Cdd:smart00145    2 PLDIEEREQLEAILK---LDPTYELTEEEKDLIWKFRHYYltNNPKA-LPKFL-LSVKWSDADeVAQALSLLLSWAPLDP 76

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590   783 LEALGLLTSSFPDQEIRKVAVQQLDNLLNDELLEFLPQLVQAVKFEWNLESPLVQLLLHRSLQSIQIAHRLYWLLKDAQN 862
Cdd:smart00145   77 EDALELLDPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELH 156

                           170       180
                    ....*....|....*....|....*..
gi 2124530590   863 EAYFKSWYQKLLAALQFCAGKALSDEF 889
Cdd:smart00145  157 DPHVSIRFGLLLEAYLRGCGTHLKELL 183
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 724-865 3.58e-23

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: 98.17  E-value: 3.58e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  724 KQSPLL-LSEEKRRYLWFYRFYCNNENCSLPLVLGSAPGWDERTVSEMHDISRRWKFSHPLEALGLLTSSFPDQEIRKVA 802
Cdd:pfam00613   18 AYDPLSkLTAEEKDLIWKFRYYLMLVPKALTKLLLSVKWSDLSEVAEALSLLLKWAPIDPVDALELLDPKFPDPEVRQYA 97

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 2124530590  803 VQQLDNLLNDELLEFLPQLVQAVKFEWNLESPLVQLLLHRSLQSIQIAHRLYWLLK-DAQNEAY 865
Cdd:pfam00613   98 VKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKsEIHDEEV 161
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 730-858 2.12e-21

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: 92.76  E-value: 2.12e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  730 LSEEKRRYLWFYRFYCNNENCSLPLVLGSAPgWDERT-VSEMHDISRRWKFSHPLEALGLLTSSFPDQEIRKVAVQQLDN 808
Cdd:cd00872     19 LTEEDKELLWKLRHECRKKPQALPKLLLSVK-WNKRDdVAQMYQLLKRWPKLKPEQALELLDCNFPDEHVREFAVRCLEK 97

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 2124530590  809 LLNDELLEFLPQLVQAVKFEWNLESPLVQLLLHRSLQSIQIAHRLYWLLK 858
Cdd:cd00872     98 LSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLR 147
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
 945-1147 5.83e-18

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: 84.25  E-value: 5.83e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  945 IKGIDrDACSYFRSNALPLKITFLNANpmGKNISVIFKAGDDLRQDMLVLQIIQVMDNIWLQEG----LDMQMIIYRCLS 1020
Cdd:cd05164      1 IASFD-PRVRILASLQKPKKITILGSD--GKEYPFLVKGDDDLRKDERVMQLFQLLNTLLEKDKetrkRNLTIRTYSVVP 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1021 TGKGQGLVQLVPDAVTLakihrrsgligplkENTIKKWFSRHNHLKVDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNI 1100
Cdd:cd05164     78 LSSQSGLIEWVDNTTTL--------------KPVLKKWFNETFPDPTQWYEARSNYTKSTAVMSMVGYIIGLGDRHLENI 143

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*...
gi 2124530590 1101 ML-TKSGHMFHIDFGKFLGHAQTFGgiKRDRAPFIFTSEMEYFITEGG 1147
Cdd:cd05164    144 LIdTKTGEVVHIDFGMIFNKGKTLP--VPEIVPFRLTRNIINGMGPTG 189
PIKKc_DNA-PK cd05172
Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, ...
 956-1120 1.19e-15

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: 78.00  E-value: 1.19e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  956 FRSNALPLKITFLNANpmGKNISVIFKAGDDLRQDMLVLQIIQVMDNIWLQE----GLDMQMIIYRCLSTGKGQGLVQLV 1031
Cdd:cd05172     11 LSSKRRPKRITIRGSD--EKEYKFLVKGGEDLRQDQRIQQLFDVMNNILASDpacrQRRLRIRTYQVIPMTSRLGLIEWV 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1032 PDAVTLAKIhrrsgligpLKENTIKKWFSRhnhLKVDYE--KALR-NFFYSCAGWCVVTFILGVCDRHNDNIML-TKSGH 1107
Cdd:cd05172     89 DNTTPLKEI---------LENDLLRRALLS---LASSPEafLALRsNFARSLAAMSICGYILGIGDRHLSNFLVdLSTGR 156

                          170
                   ....*....|...
gi 2124530590 1108 MFHIDFGKFLGHA 1120
Cdd:cd05172    157 LIGIDFGHAFGSA 169
PI3Ka_III cd00870
Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is ...
 710-858 1.24e-15

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: 75.83  E-value: 1.24e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  710 PPKECLKHIARLSQKQSPLLLSEEKRRYLWFYRFYCNNENCSLPLVLGSAPGWDERTVSEMHDISRRWKFSHPLEALGLL 789
Cdd:cd00870      6 PNSKERKELNKILKYPPTTKLTDEEKDLIWKFRFYLTNNKKALTKFLKSVNWSDEQEVKQALELMPKWAKIDIEDALELL 85

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 2124530590  790 TSSFPDQEIRKVAVQQLDNLLNDELLEFLPQLVQAVKFE-------WNLESPLVQLLLHRSLQSIQIAHRLYWLLK 858
Cdd:cd00870     86 SPYFTNPVVRKYAVSRLKLASDEELLLYLLQLVQALKYEnldlsplPRLDSPLADFLIERALKNPKLANFLYWYLK 161
PX smart00312
PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function ...
 1274-1362 1.40e-14

PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function present in phox proteins, PLD isoforms, a PI3K isoform.


Pssm-ID: 214610  Cd Length: 105  Bit Score: 70.84  E-value: 1.40e-14
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  1274 FSKKTSNLYLIQVTHS-NDETSLTEKSFDQFSKLHSQLQKHFASLSLPEFPHWWHLPFTNSDHNRF-----RDLNRYMEQ 1347
Cdd:smart00312    7 IGDGKHYYYVIEIETKtGLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRLNNFSEEFiekrrRGLEKYLQS 86

                            90
                    ....*....|....*
gi 2124530590  1348 ILNGSYEVANNEVVK 1362
Cdd:smart00312   87 LLNHPELINHSEVVL 101
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
 961-1114 3.13e-14

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: 74.88  E-value: 3.13e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  961 LPLKITFLNANpmGKNISVIFKAGDDLRQDMLVLQIIQVMdNIWLQEGL-----DMQMIIYRCLSTGKGQGLVQLVPDAV 1035
Cdd:cd05171     16 LPKIITCIGSD--GKKYKQLVKGGDDLRQDAVMEQVFELV-NQLLKRDKetrkrKLRIRTYKVVPLSPRSGVLEFVENTI 92

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1036 TLAKI----HRRSGL-----IGPLKENTIKKWFSRHNHLKVD-----YEK-------ALRNFFY---------------- 1078
Cdd:cd05171     93 PLGEYlvgaSSKSGAharyrPKDWTASTCRKKMREKAKASAEerlkvFDEicknfkpVFRHFFLekfpdpsdwferrlay 172

                          170       180       190
                   ....*....|....*....|....*....|....*....
gi 2124530590 1079 --SCAGWCVVTFILGVCDRHNDNIML-TKSGHMFHIDFG 1114
Cdd:cd05171    173 trSVATSSIVGYILGLGDRHLNNILIdQKTGELVHIDLG 211
PX_domain cd06093
The Phox Homology domain, a phosphoinositide binding module; The PX domain is a ...
 1265-1362 1.38e-12

The Phox Homology domain, a phosphoinositide binding module; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to membranes. Proteins containing PX domains interact with PIs and have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. Many members of this superfamily bind phosphatidylinositol-3-phosphate (PI3P) but in some cases, other PIs such as PI4P or PI(3,4)P2, among others, are the preferred substrates. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction, as in the cases of p40phox, p47phox, and some sorting nexins (SNXs). The PX domain is conserved from yeast to humans and is found in more than 100 proteins. The majority of PX domain-containing proteins are SNXs, which play important roles in endosomal sorting.


Pssm-ID: 132768 [Multi-domain]  Cd Length: 106  Bit Score: 65.46  E-value: 1.38e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1265 SIQKATILGFSKKTSNLYLIQVTHSNDETSLTEKSFDQFSKLHSQLQKHFASLSLPEFPHWWHLPFTNSD--HNRFRDLN 1342
Cdd:cd06093      3 SIPDYEKVKDGGKKYVVYIIEVTTQGGEEWTVYRRYSDFEELHEKLKKKFPGVILPPLPPKKLFGNLDPEfiEERRKQLE 82

                           90       100
                   ....*....|....*....|
gi 2124530590 1343 RYMEQILNgSYEVANNEVVK 1362
Cdd:cd06093     83 QYLQSLLN-HPELRNSEELK 101
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 543-627 6.94e-12

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 63.13  E-value: 6.94e-12
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590   543 SHLSFTVYAAHNIPETWVHSYKAFSFSCRLTYAGKKLCQVRNYRNIPvkklFFFLVNWDETINFPLEIKSLPRESMLTIK 622
Cdd:smart00142   11 RNLVITIALIHGIPLNWSRDYSDLYVEIQLYHGGKLLCLPVSTSYKP----FFPSVKWNEWLTFPIQISDLPREARLCIT 86


                    ....*
gi 2124530590   623 LFGII 627
Cdd:smart00142   87 IYAVK 91
PX pfam00787
PX domain; PX domains bind to phosphoinositides.
 1286-1362 1.35e-10

PX domain; PX domains bind to phosphoinositides.


Pssm-ID: 459940  Cd Length: 84  Bit Score: 58.79  E-value: 1.35e-10
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 2124530590 1286 VTHSNDETSLTEKSFDQFSKLHSQLQKHFASLSLPEFPHW-WHLPFTNSD-HNRFRDLNRYMEQILNGSyEVANNEVVK 1362
Cdd:pfam00787    1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSVIIPPLPPKrWLGRYNEEFiEKRRKGLEQYLQRLLQHP-ELRNSEVLL 78
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 945-1113 1.55e-10

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: 62.91  E-value: 1.55e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  945 IKGIDRDAcSYFRSNALPLKITFLNANpmGKNISVIFKAGDDLRQDMLVLQIIQVMDNIWLQ--EGLDMQMII--YRCLS 1020
Cdd:cd00892      1 ISGFEDEV-EIMPSLQKPKKITLVGSD--GKKYPFLCKPKDDLRKDARMMEFNTLINRLLSKdpESRRRNLHIrtYAVIP 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1021 TGKGQGLVQLVPDAVTLAKIhrrsglIGPLKENTIKKWFSRHNHLKVDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNI 1100
Cdd:cd00892     78 LNEECGIIEWVPNTVTLRSI------LSTLYPPVLHEWFLKNFPDPTAWYEARNNYTRSTAVMSMVGYILGLGDRHGENI 151

                          170
                   ....*....|....
gi 2124530590 1101 ML-TKSGHMFHIDF 1113
Cdd:cd00892    152 LFdSTTGDVVHVDF 165
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 569-648 1.90e-09

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: 57.38  E-value: 1.90e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  569 SCRLTYAGKKLCQVRNYRNIPVKKLFFflvNWDETINFPLEIKSLPRESMLTIKLFGIIHASNTANLLAWTCLPLFPKDK 648
Cdd:pfam00792    8 ECQLYHGGKPLCLPVSTRYVPFSNSSI---KWNEWITFPIQISDLPRSARLCITIWDVSGPEKSFVPIGWVNTSLFDKKG 84
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 982-1114 7.47e-08

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: 55.57  E-value: 7.47e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  982 KAGDDLRQDMLVLQ----IIQVMDNIWLQEGLDMQMIIYRC--LSTGkgQGLVQLVPDAVTLAKI---HRRSGLIGPLKE 1052
Cdd:cd05169     35 KGHEDLRLDERVMQlfglVNTLLKNDSETSRRNLSIQRYSVipLSPN--SGLIGWVPGCDTLHSLirdYREKRKIPLNIE 112

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1053 N-TIKKWFSRHNHL----KVD-YEKALR--------------------------NFFYSCAGWCVVTFILGVCDRHNDNI 1100
Cdd:cd05169    113 HrLMLQMAPDYDNLtliqKVEvFEYALEntpgddlrrvlwlkspsseawlerrtNFTRSLAVMSMVGYILGLGDRHPSNI 192

                          170
                   ....*....|....*
gi 2124530590 1101 ML-TKSGHMFHIDFG 1114
Cdd:cd05169    193 MLdRLTGKVIHIDFG 207
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
 974-1114 1.14e-07

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


Pssm-ID: 270870 [Multi-domain]  Cd Length: 136  Bit Score: 52.06  E-value: 1.14e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  974 GKNISVIFKAGDDlRQDMLVLQIIQVMDNiwLQEGLDMQMIIYRCLSTGKGQGLVQLVPDAVtlakihrrSGliGPLKEN 1053
Cdd:cd13968     16 CTTIGVAVKIGDD-VNNEEGEDLESEMDI--LRRLKGLELNIPKVLVTEDVDGPNILLMELV--------KG--GTLIAY 82

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 2124530590 1054 TIKKWFSrhnhlkvdyEKALRNFFYSCAGWCVVTFILGVC--DRHNDNIMLTKSGHMFHIDFG 1114
Cdd:cd13968     83 TQEEELD---------EKDVESIMYQLAECMRLLHSFHLIhrDLNNDNILLSEDGNVKLIDFG 136
C2_PI3K_like cd08380
C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes ...
 545-690 6.43e-07

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: 50.44  E-value: 6.43e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  545 LSFTVYAAHNIPETWVHSYKaFSFSCRLTYAGKKLCQVRNYRNIPvkklFFFLVNWDETINFPLEIKSLPRESMLTiklF 624
Cdd:cd08380     10 LRIKIHGITNINLLDSEDLK-LYVRVQLYHGGEPLCPPQSTKKVP----FSTSVTWNEWLTFDILISDLPREARLC---L 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2124530590  625 GIIHASNTAN----LLAWTCLPLFP-KDKSIPGPVLFSM-TSQSEPPIEMIAPGVwdISQPSPVILQIDFPA 690
Cdd:cd08380     82 SIYAVSEPGSkkevPLGWVNVPLFDyKGKLRQGMITLNLwPGKKTDPRIACTPCN--NSNENSTRLLIELPE 151
PX_SNX27 cd06886
The phosphoinositide binding Phox Homology domain of Sorting Nexin 27; The PX domain is a ...
 1295-1348 4.79e-06

The phosphoinositide binding Phox Homology domain of Sorting Nexin 27; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX27 contains an N-terminal PDZ domain followed by a PX domain and a Ras-Associated (RA) domain. It binds G protein-gated potassium (Kir3) channels, which play a role in neuronal excitability control, through its PDZ domain. SNX27 downregulates Kir3 channels by promoting their movement in the endosome, reducing surface expression and increasing degradation. SNX27 also associates with 5-hydroxytryptamine type 4 receptor (5-HT4R), cytohesin associated scaffolding protein (CASP), and diacylglycerol kinase zeta, and may play a role in their intracellular trafficking and endocytic recycling. The SNX27 PX domain preferentially binds to phosphatidylinositol-3-phosphate (PI3P) and is important for targeting to the early endosome.


Pssm-ID: 132796  Cd Length: 106  Bit Score: 46.63  E-value: 4.79e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 2124530590 1295 LTEKSFDQFSKLHSQLQKHFASLSLPEFPHWWhlPFTNSDHN---RFRDLNRYMEQI 1348
Cdd:cd06886     33 LCSRRYREFANLHQNLKKEFPDFQFPKLPGKW--PFSLSEQQldaRRRGLEQYLEKV 87
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
 962-1113 1.07e-04

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: 45.71  E-value: 1.07e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  962 PLKITFLNANpmGKNISVIFKAGDDLRQD---MLVLQIIQVMdniwLQ--EGLDMQMIIYRCLST---GKGQGLVQLVPD 1033
Cdd:cd05170     17 PKKLVFLGSD--GKRYPYLFKGLEDLHLDeriMQFLSIVNAM----LAsdNEHRRRRYRARHYSVtplGPRSGLIQWVDG 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1034 AVTLAKIHRR-------------------------------SGLIGPLKENTIKKWFSRH----NHLKVDYE-------- 1070
Cdd:cd05170     91 ATPLFSLYKRwqqrraaaqaqknqdsgstpppvprpselfyNKLKPALKAAGIRKSTSRRewplEVLRQVLEelvaetpr 170

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 2124530590 1071 ------------------KALRNFFYSCAGWCVVTFILGVCDRHNDNIMLT-KSGHMFHIDF 1113
Cdd:cd05170    171 dllarelwcsspssaewwRVTQRFARSLAVMSMIGYIIGLGDRHLDNILVDlSTGEVVHIDY 232
PX_PI3K_C2_beta cd07290
The phosphoinositide binding Phox Homology Domain of the Beta Isoform of Class II ...
 1274-1361 1.15e-04

The phosphoinositide binding Phox Homology Domain of the Beta Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. 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. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. 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 PX domain, and a second C2 domain at the C-terminus. 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. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


Pssm-ID: 132823  Cd Length: 109  Bit Score: 42.99  E-value: 1.15e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1274 FSKKTSNLYLIQVTHSN-DETSLTEKSFDQFSKLHSQLQKHFASLSLPEFPHWWHLPFTNSD---HNRFRDLNRYMEQIL 1349
Cdd:cd07290     11 FNPSKGYAYVVKVQREGhKEATFVQRTFEEFQELHNKLRLLFPSSKLPSFPSRFVIGRSRGEavaERRKEELNGYIWHLI 90

                           90
                   ....*....|..
gi 2124530590 1350 NGSYEVANNEVV 1361
Cdd:cd07290     91 HAPPEVAECDLV 102
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 273-367 1.39e-04

PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding domains in their N-termini. These regions show some similarity (although not highly significant similarity) to Ras-binding pfam00788 domains (unpublished observation).


Pssm-ID: 395642  Cd Length: 106  Bit Score: 42.67  E-value: 1.39e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590  273 STTTAFPYQLLSNTKFHVNIFTDNSTQVLHFMPYANYLVKDLIAETlhFCKNDQLFPK-----DHLLSVCGYEEFLQNNY 347
Cdd:pfam00794    2 STVSPEPLPKLINNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQA--LTKKLSVHTQgdvtdDYVLKVCGRDEYLLGDH 79

                           90       100
                   ....*....|....*....|...
gi 2124530590  348 SLGSH---RIFQKDKSVIQLNLQ 367
Cdd:pfam00794   80 PLGQFeyiRNCLKSGREPHLTLV 102
PX_PI3K_C2_alpha cd07289
The phosphoinositide binding Phox Homology Domain of the Alpha Isoform of Class II ...
 1268-1361 4.38e-04

The phosphoinositide binding Phox Homology Domain of the Alpha Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. 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. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. 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 PX domain, and a second C2 domain at the C-terminus. 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. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


Pssm-ID: 132822  Cd Length: 109  Bit Score: 41.07  E-value: 4.38e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 2124530590 1268 KATILGFSKKTSN----LYLIQVTHS-NDETSLTEKSFDQFSKLHSQLQKHFASLSLPEFPHWWHLPFTNSDH---NRFR 1339
Cdd:cd07289      1 EVSVFTYHKRYNPdkhyIYVVRILREgQIEPSFVFRTFDEFQELHNKLSILFPLWKLPGFPNKMVLGRTHIKDvaaKRKV 80

                           90       100
                   ....*....|....*....|..
gi 2124530590 1340 DLNRYMEQILNGSYEVANNEVV 1361
Cdd:cd07289     81 ELNSYIQSLMNSSTEVAECDLV 102
PX_UP2_fungi cd06869
The phosphoinositide binding Phox Homology domain of uncharacterized fungal proteins; The PX ...
 1275-1324 1.70e-03

The phosphoinositide binding Phox Homology domain of uncharacterized fungal proteins; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized fungal proteins containing a PX domain. PX domain harboring proteins have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction.


Pssm-ID: 132779  Cd Length: 119  Bit Score: 39.57  E-value: 1.70e-03
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|..
gi 2124530590 1275 SKKTSNLYLIQVTHSNDE--TSLTEKSFDQFSKLHSQLQKHFASLSLPEFPH 1324
Cdd:cd06869     29 RSKHHYEFIIRVRREGEEyrTIYVARRYSDFKKLHHDLKKEFPGKKLPKLPH 80
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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