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Conserved domains on  [gi|1340723175|ref|NP_997566|]
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phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit gamma isoform 1 [Mus musculus]

Protein Classification

PI3Kc_C2_gamma and PX_PI3K_C2_gamma domain-containing protein (domain architecture ID 10134000)

protein containing domains C2A_PI3K_class_II, PI3Ka, PI3Kc_C2_gamma, and PX_PI3K_C2_gamma

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 ...
886-1239 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  Cd Length: 354  Bit Score: 708.20  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  886 NEELSKEQKLVKLLGDIGEKVKSASDPQRKDVLKKEIGSLEEFFKDIKTCHLPLNPALCIKGIDRDACSYFTSNASPLKI 965
Cdd:cd05177      1 NKEFSKETKLISILIDAAEKVKTASDTRRKEVLKREASRLEDFFQDVVSCCLPLNPALRVKGIDADACSYFTSNAAPLKI 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  966 TFINANPMGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIHLHSG 1045
Cdd:cd05177     81 SFINANPLAKNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYRCLSTGKTQGLVQMVPDAVTLAKIHRESG 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1046 LIGPLKENTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQTFGG 1125
Cdd:cd05177    161 LIGPLKENTIEKWFHMHNKLKEDYDKAVRNFFHSCAGWCVVTFILGVCDRHNDNIMLTHSGHMFHIDFGKFLGHAQTFGS 240
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1126 IKRDRAPFIFTSEMEYFITEGGKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDLKYVHNNLRPQ 1205
Cdd:cd05177    241 IKRDRAPFIFTSEMEYFITEGGKKPQRFQRFVELCCRAYNIVRKHSQLLLNLLEMMLHAGLPELKDIQDLKYVYNNLRPQ 320
                          330       340       350
                   ....*....|....*....|....*....|....
gi 1340723175 1206 DTDLEATSHFTKKIKESLECFPVKLNNLIHTLAQ 1239
Cdd:cd05177    321 DTDLEATSYFTKKIKESLECFPVKLNNLIHTLAQ 354
PI3Ka super family cl00271
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
713-880 1.41e-70

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: 233.50  E-value: 1.41e-70
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  713 ECLKHIAKLSQKKSPLLLSEEKRRYLWFYRLYCNNENSSLPLVLGSAPGWDEETVSEMHAILRRWTFSHPWEALGLLTSR 792
Cdd:cd00869      2 ETQEKLLDLIQKQSTYTLSTEDKDLLWEKRLYCTNEPNALPLVLASAPSWDWANLMDVYQLLHQWAPLRPLIALELLLPK 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  793 FPDQDIREVAVQQLDTLLTDELLDCLPQLVQAVKFEWNLESPLVELLLRRSLQSIRVAHRLYWLLRDAQGEAYFKSWYQE 872
Cdd:cd00869     82 FPDQEVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALDDCYFSSAYQD 161

                   ....*...
gi 1340723175  873 LLAALQFC 880
Cdd:cd00869    162 LGAALRCQ 169
PX_PI3K_C2_gamma cd06896
The phosphoinositide binding Phox Homology Domain of the Gamma Isoform of Class II ...
1268-1368 5.60e-61

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: 203.22  E-value: 5.60e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1268 RVTILGFSKTHSNLYLMEVTCSDNRRSLTKKSFEQFYRLHSQMQKQFSSLALPEFPHWWHLPFTDSDHKRIRDLSHYVEQ 1347
Cdd:cd06896      1 RATILGFSKKSSNLYLVQVTQSCNLVSLTEKSFEQFSELHSQLQKQFPSLALPEFPHWWHLPFTDSDHKRVRDLNHYLEQ 80
                           90       100
                   ....*....|....*....|.
gi 1340723175 1348 VLRGSYEVANSDCVLSFFLSE 1368
Cdd:cd06896     81 LLSGSREVANSDCVLSFFLSE 101
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
538-698 1.48e-49

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: 173.31  E-value: 1.48e-49
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  538 HAGLQSHLSFTVCSLHNVPETWAHSYKAFSFSCWLTYAGKKLCQVKSCRPLPVTKSFSLLVNWNEIINFPLEIKSLPRES 617
Cdd:cd04012      3 ASTVTDLLSVTVSSLHRIPPTWVQSFEDFYLSCSLYHGGRLLCSPVTTKPVKITKSFFPRVVWDEWIEFPIPVCQLPRES 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  618 MLIIKLFGIDSA--------THSTNLLAWTCLPLFP-RQESVLGSRLFSVTLQSEPPIEMIAPgVWDGSQPSPLTLQIDF 688
Cdd:cd04012     83 RLVLTLYGTTSSpdggsnkqRMGPEELGWVSLPLFDfRGVLRQGSLLLGLWPPSKDNPLGPAP-PPLFEQPDRVILQIDF 161
                          170
                   ....*....|
gi 1340723175  689 PDAGWEYLKP 698
Cdd:cd04012    162 PSSAFDVIFP 171
C2 super family cl14603
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
1390-1502 1.18e-39

C2 domain; The C2 domain was first identified in PKC. 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.


The actual alignment was detected with superfamily member cd08381:

Pssm-ID: 417471 [Multi-domain]  Cd Length: 122  Bit Score: 143.20  E-value: 1.18e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1390 SPKVQLLMTYEDSRLTILVKHLKNIHLPDGSVPSAHVEIYLLPHPSEVRRKKTKCVPKCTDPTYNEIVVYDE--VLGLQG 1467
Cdd:cd08381      1 GGQVKLSISYKNGTLFVMVMHAKNLPLLDGSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDGlpVEDLQQ 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1340723175 1468 HVLMLIVKSKTVFVgaVNIQLCSVPLN---------EEKWYPLG 1502
Cdd:cd08381     81 RVLQVSVWSHDSLV--ENEFLGGVCIPlkkldlsqeTEKWYPLG 122
 
Name Accession Description Interval E-value
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
886-1239 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  Cd Length: 354  Bit Score: 708.20  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  886 NEELSKEQKLVKLLGDIGEKVKSASDPQRKDVLKKEIGSLEEFFKDIKTCHLPLNPALCIKGIDRDACSYFTSNASPLKI 965
Cdd:cd05177      1 NKEFSKETKLISILIDAAEKVKTASDTRRKEVLKREASRLEDFFQDVVSCCLPLNPALRVKGIDADACSYFTSNAAPLKI 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  966 TFINANPMGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIHLHSG 1045
Cdd:cd05177     81 SFINANPLAKNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYRCLSTGKTQGLVQMVPDAVTLAKIHRESG 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1046 LIGPLKENTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQTFGG 1125
Cdd:cd05177    161 LIGPLKENTIEKWFHMHNKLKEDYDKAVRNFFHSCAGWCVVTFILGVCDRHNDNIMLTHSGHMFHIDFGKFLGHAQTFGS 240
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1126 IKRDRAPFIFTSEMEYFITEGGKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDLKYVHNNLRPQ 1205
Cdd:cd05177    241 IKRDRAPFIFTSEMEYFITEGGKKPQRFQRFVELCCRAYNIVRKHSQLLLNLLEMMLHAGLPELKDIQDLKYVYNNLRPQ 320
                          330       340       350
                   ....*....|....*....|....*....|....
gi 1340723175 1206 DTDLEATSHFTKKIKESLECFPVKLNNLIHTLAQ 1239
Cdd:cd05177    321 DTDLEATSYFTKKIKESLECFPVKLNNLIHTLAQ 354
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
979-1193 3.60e-72

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: 241.05  E-value: 3.60e-72
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175   979 VIFKAGDDLRQDMLALQIIQVMDNAWLQE----GLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIHLHS---------- 1044
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYrkqkgkvldl 80
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  1045 ---------------GLIGPLKENTIKKWFSQHN-HLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHM 1108
Cdd:smart00146   81 rsqtatrlkklelflEATGKFPDPVLYDWFTKKFpDPSEDYFEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160
                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  1109 FHIDFGKFLGHAQTFGGIKrDRAPFIFTSEMEYFITEggknTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPE 1188
Cdd:smart00146  161 FHIDFGFILGNGPKLFGFP-ERVPFRLTPEMVDVMGD----SGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLPD 235

                    ....*
gi 1340723175  1189 LRGIE 1193
Cdd:smart00146  236 WRSGK 240
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
713-880 1.41e-70

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: 233.50  E-value: 1.41e-70
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  713 ECLKHIAKLSQKKSPLLLSEEKRRYLWFYRLYCNNENSSLPLVLGSAPGWDEETVSEMHAILRRWTFSHPWEALGLLTSR 792
Cdd:cd00869      2 ETQEKLLDLIQKQSTYTLSTEDKDLLWEKRLYCTNEPNALPLVLASAPSWDWANLMDVYQLLHQWAPLRPLIALELLLPK 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  793 FPDQDIREVAVQQLDTLLTDELLDCLPQLVQAVKFEWNLESPLVELLLRRSLQSIRVAHRLYWLLRDAQGEAYFKSWYQE 872
Cdd:cd00869     82 FPDQEVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALDDCYFSSAYQD 161

                   ....*...
gi 1340723175  873 LLAALQFC 880
Cdd:cd00869    162 LGAALRCQ 169
PX_PI3K_C2_gamma cd06896
The phosphoinositide binding Phox Homology Domain of the Gamma Isoform of Class II ...
1268-1368 5.60e-61

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: 203.22  E-value: 5.60e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1268 RVTILGFSKTHSNLYLMEVTCSDNRRSLTKKSFEQFYRLHSQMQKQFSSLALPEFPHWWHLPFTDSDHKRIRDLSHYVEQ 1347
Cdd:cd06896      1 RATILGFSKKSSNLYLVQVTQSCNLVSLTEKSFEQFSELHSQLQKQFPSLALPEFPHWWHLPFTDSDHKRVRDLNHYLEQ 80
                           90       100
                   ....*....|....*....|.
gi 1340723175 1348 VLRGSYEVANSDCVLSFFLSE 1368
Cdd:cd06896     81 LLSGSREVANSDCVLSFFLSE 101
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
977-1190 3.36e-59

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


Pssm-ID: 395364 [Multi-domain]  Cd Length: 241  Bit Score: 203.72  E-value: 3.36e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  977 ISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMI-TYGCLSTGRAQGFIEMVPDAVTLAKIHLHSG---------- 1045
Cdd:pfam00454    2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLRRLkPYSVIPLGPKCGIIEWVPNSETLAYILDEYGengvpptamv 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1046 ------------------LIGPLKENTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIML-TKSG 1106
Cdd:pfam00454   82 kilhsalnypklklefesRISLPPKVGLLQWFVKKSPDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTTG 161
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1107 HMFHIDFGKFLGHAQTFGGIKrDRAPFIFTSEMEYFITEggknTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGL 1186
Cdd:pfam00454  162 KLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAMGP----SGDEGLFRELCETAYEALRRNLNLLTNLLKLMVADGL 236

                   ....
gi 1340723175 1187 PELR 1190
Cdd:pfam00454  237 PDWS 240
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
538-698 1.48e-49

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: 173.31  E-value: 1.48e-49
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  538 HAGLQSHLSFTVCSLHNVPETWAHSYKAFSFSCWLTYAGKKLCQVKSCRPLPVTKSFSLLVNWNEIINFPLEIKSLPRES 617
Cdd:cd04012      3 ASTVTDLLSVTVSSLHRIPPTWVQSFEDFYLSCSLYHGGRLLCSPVTTKPVKITKSFFPRVVWDEWIEFPIPVCQLPRES 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  618 MLIIKLFGIDSA--------THSTNLLAWTCLPLFP-RQESVLGSRLFSVTLQSEPPIEMIAPgVWDGSQPSPLTLQIDF 688
Cdd:cd04012     83 RLVLTLYGTTSSpdggsnkqRMGPEELGWVSLPLFDfRGVLRQGSLLLGLWPPSKDNPLGPAP-PPLFEQPDRVILQIDF 161
                          170
                   ....*....|
gi 1340723175  689 PDAGWEYLKP 698
Cdd:cd04012    162 PSSAFDVIFP 171
C2B_PI3K_class_II cd08381
C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are ...
1390-1502 1.18e-39

C2 domain second 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. 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 second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176027 [Multi-domain]  Cd Length: 122  Bit Score: 143.20  E-value: 1.18e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1390 SPKVQLLMTYEDSRLTILVKHLKNIHLPDGSVPSAHVEIYLLPHPSEVRRKKTKCVPKCTDPTYNEIVVYDE--VLGLQG 1467
Cdd:cd08381      1 GGQVKLSISYKNGTLFVMVMHAKNLPLLDGSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDGlpVEDLQQ 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1340723175 1468 HVLMLIVKSKTVFVgaVNIQLCSVPLN---------EEKWYPLG 1502
Cdd:cd08381     81 RVLQVSVWSHDSLV--ENEFLGGVCIPlkkldlsqeTEKWYPLG 122
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
937-1221 8.52e-39

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 159.18  E-value: 8.52e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  937 LPLNPALCIKGIDRDACSYFTSNASPLKITFINANpmGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGL----DMQ 1012
Cdd:COG5032   1759 LLDKPFVLIERFEPEVSVVKSHLQRPRRLTIRGSD--GKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLW 1836
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1013 MITYGCLSTGRAQGFIEMVPDAVTLAKIHL---------------------HSGLIGPLK---------ENTIKKWFSQH 1062
Cdd:COG5032   1837 IRPYKVIPLSPGSGIIEWVPNSDTLHSILReyhkrknisidqekklaarldNLKLLLKDEfftkatlksPPVLYDWFSES 1916
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1063 NHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTK-SGHMFHIDFGKFLGHAQTFGGIKrDRAPFIFTSEMEY 1141
Cdd:COG5032   1917 FPNPEDWLTARTNFARSLAVYSVIGYILGLGDRHPGNILIDRsSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVE 1995
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1142 FIteGGKNTQHFqdFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDLKYVHNNLRPQDTDLeatshFTKKIKE 1221
Cdd:COG5032   1996 AM--GVSGVEGS--FRELCETAFRALRKNADSLMNVLELFVRDPLIEWRRLPCFREIQNNEIVNVLER-----FRLKLSE 2066
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
711-877 6.21e-28

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: 111.97  E-value: 6.21e-28
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175   711 PRECLKHIAKlsqKKSPLLLSEEKRRYLWFYRLYC-NNENSSLPLVLGSAPGWDEETVSEMHAILRRWTFSHPWEALGLL 789
Cdd:smart00145    7 EREQLEAILK---LDPTYELTEEEKDLIWKFRHYYlTNNPKALPKFLLSVKWSDADEVAQALSLLLSWAPLDPEDALELL 83
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175   790 TSRFPDQDIREVAVQQLDTLLTDELLDCLPQLVQAVKFEWNLESPLVELLLRRSLQSIRVAHRLYWLLRDAQGEAYFKSW 869
Cdd:smart00145   84 DPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHVSIR 163

                    ....*...
gi 1340723175   870 YQELLAAL 877
Cdd:smart00145  164 FGLLLEAY 171
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
724-858 1.09e-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: 99.71  E-value: 1.09e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  724 KKSPLL-LSEEKRRYLWFYRLYCNNENSSLPLVLGSAPGWDEETVSEMHAILRRWTFSHPWEALGLLTSRFPDQDIREVA 802
Cdd:pfam00613   18 AYDPLSkLTAEEKDLIWKFRYYLMLVPKALTKLLLSVKWSDLSEVAEALSLLLKWAPIDPVDALELLDPKFPDPEVRQYA 97
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1340723175  803 VQQLDTLLTDELLDCLPQLVQAVKFEWNLESPLVELLLRRSLQSIRVAHRLYWLLR 858
Cdd:pfam00613   98 VKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLK 153
PX smart00312
PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function ...
1274-1365 3.99e-16

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: 75.46  E-value: 3.99e-16
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  1274 FSKTHSNLYLMEVTCSDN-RRSLTKKSFEQFYRLHSQMQKQFSSLALPEFPHWWHLPFTDSD-----HKRIRDLSHYVEQ 1347
Cdd:smart00312    7 IGDGKHYYYVIEIETKTGlEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRLNNFseefiEKRRRGLEKYLQS 86
                            90
                    ....*....|....*...
gi 1340723175  1348 VLRGSYEVANSDCVLSFF 1365
Cdd:smart00312   87 LLNHPELINHSEVVLEFL 104
PX pfam00787
PX domain; PX domains bind to phosphoinositides.
1286-1368 4.79e-13

PX domain; PX domains bind to phosphoinositides.


Pssm-ID: 395635  Cd Length: 84  Bit Score: 65.73  E-value: 4.79e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1286 VTCSDNRRSLTKKSFEQFYRLHSQMQKQFSSLALPEFPHW-WHLPFTDSD-HKRIRDLSHYVEQVLRGSyEVANSDCVLS 1363
Cdd:pfam00787    1 LPTFDLEEWSVRRRYSDFVELHKQLLRKFPSLIIPPLPPKvWFGRYNEEFiEKRRKGLEQYLQRLLQHP-ELRNSEVLLE 79

                   ....*
gi 1340723175 1364 FFLSE 1368
Cdd:pfam00787   80 FLESD 84
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
543-626 3.87e-10

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 58.13  E-value: 3.87e-10
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175   543 SHLSFTVCSLHNVPETWAHSYKAFSFSCWLTYAGKKLCQVKSCRPlpvtKSFSLLVNWNEIINFPLEIKSLPRESMLIIK 622
Cdd:smart00142   11 RNLVITIALIHGIPLNWSRDYSDLYVEIQLYHGGKLLCLPVSTSY----KPFFPSVKWNEWLTFPIQISDLPREARLCIT 86

                    ....
gi 1340723175   623 LFGI 626
Cdd:smart00142   87 IYAV 90
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
569-644 9.87e-10

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: 58.15  E-value: 9.87e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  569 SCWLTYAGKKLCqvkscrpLPVT---KSFS-LLVNWNEIINFPLEIKSLPRESMLIIKLFGIDSATHSTNLLAWTCLPLF 644
Cdd:pfam00792    8 ECQLYHGGKPLC-------LPVStryVPFSnSSIKWNEWITFPIQISDLPRSARLCITIWDVSGPEKSFVPIGWVNTSLF 80
C2 pfam00168
C2 domain;
1403-1501 4.64e-09

C2 domain;


Pssm-ID: 395116 [Multi-domain]  Cd Length: 104  Bit Score: 55.40  E-value: 4.64e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1403 RLTILVKHLKNIHLPDGSVPS-AHVEIYLLphpSEVRRKKTKCVPKCTDPTYNEIVVYdEVLGLQGHVLMLIVK-----S 1476
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDLNGKSdPYVKVSLL---DGKQKKKTKVVKNTLNPVWNETFTF-SVPDPENQVLEIEVYdydrfG 77
                           90       100
                   ....*....|....*....|....*..
gi 1340723175 1477 KTVFVGAVNIQLCSVPLNE--EKWYPL 1501
Cdd:pfam00168   78 RDDFLGEVRIPLSELLLGEglDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
1403-1498 3.10e-07

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 49.79  E-value: 3.10e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  1403 RLTILVKHLKNI-HLPDGSVPSAHVEIYLLPHPSEVrrKKTKCVPKCTDPTYNEIVVYDeVLGLQGHVLMLIVKSKTV-- 1479
Cdd:smart00239    1 TLTVKIISARNLpPKDKGGKSDPYVKVSLDGDPKEK--KKTKVVKNTLNPVWNETFEFE-VPPPELAELEIEVYDKDRfg 77
                            90       100
                    ....*....|....*....|..
gi 1340723175  1480 ---FVGAVNIQLCSVPLNEEKW 1498
Cdd:smart00239   78 rddFIGQVTIPLSDLLLGGRHE 99
 
Name Accession Description Interval E-value
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
886-1239 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  Cd Length: 354  Bit Score: 708.20  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  886 NEELSKEQKLVKLLGDIGEKVKSASDPQRKDVLKKEIGSLEEFFKDIKTCHLPLNPALCIKGIDRDACSYFTSNASPLKI 965
Cdd:cd05177      1 NKEFSKETKLISILIDAAEKVKTASDTRRKEVLKREASRLEDFFQDVVSCCLPLNPALRVKGIDADACSYFTSNAAPLKI 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  966 TFINANPMGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIHLHSG 1045
Cdd:cd05177     81 SFINANPLAKNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYRCLSTGKTQGLVQMVPDAVTLAKIHRESG 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1046 LIGPLKENTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQTFGG 1125
Cdd:cd05177    161 LIGPLKENTIEKWFHMHNKLKEDYDKAVRNFFHSCAGWCVVTFILGVCDRHNDNIMLTHSGHMFHIDFGKFLGHAQTFGS 240
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1126 IKRDRAPFIFTSEMEYFITEGGKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDLKYVHNNLRPQ 1205
Cdd:cd05177    241 IKRDRAPFIFTSEMEYFITEGGKKPQRFQRFVELCCRAYNIVRKHSQLLLNLLEMMLHAGLPELKDIQDLKYVYNNLRPQ 320
                          330       340       350
                   ....*....|....*....|....*....|....
gi 1340723175 1206 DTDLEATSHFTKKIKESLECFPVKLNNLIHTLAQ 1239
Cdd:cd05177    321 DTDLEATSYFTKKIKESLECFPVKLNNLIHTLAQ 354
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
887-1239 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  Cd Length: 352  Bit Score: 579.63  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  887 EELSKEQKLVKLLGDIGEKVKSASDPQRKDVLKKEIGSLEEFFKDIKtCHLPLNPALCIKGIDRDACSYFTSNASPLKIT 966
Cdd:cd05166      2 EEFLKQHVLVQALTSIAEKVKSAKDSARENALRRELEQLASFLLENS-FRLPLDPALEVTGVDVRSCSYFNSNALPLKLV 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  967 FINANPMGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIHLHSGL 1046
Cdd:cd05166     81 FRNADPRAEPISVIFKVGDDLRQDMLTLQLIRIMDKIWLQEGLDLKMITFRCVPTGNKRGMVELVPEAETLREIQTEHGL 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1047 IGPLKENTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQTFGGI 1126
Cdd:cd05166    161 TGSFKDRPLADWLQKHNPSELEYEKAVENFIRSCAGYCVATYVLGICDRHNDNIMLKTSGHLFHIDFGKFLGDAQMFGNF 240
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1127 KRDRAPFIFTSEMEYFITEGGKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELrGIEDLKYVHNNLRPQD 1206
Cdd:cd05166    241 KRDRVPFVLTSDMAYVINGGDKPSSRFQLFVDLCCQAFNIIRKNSNLLLNLLSLMLSSGIPGV-TQDDLRYVQDALLPEL 319
                          330       340       350
                   ....*....|....*....|....*....|...
gi 1340723175 1207 TDLEATSHFTKKIKESLECFPVKLNNLIHTLAQ 1239
Cdd:cd05166    320 TDAEATAHFTRMIEESLSSKFTQLNFFIHNLAQ 352
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
887-1223 1.53e-154

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  Cd Length: 334  Bit Score: 472.06  E-value: 1.53e-154
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  887 EELSKEQKLVKLLGDIGEKVKSASDPQRKDVLKKEIGSLEEFfkdiKTCHLPLNPALCIKGIDRDACSYFTSNASPLKIT 966
Cdd:cd00891      2 EELLKQVKVLDELKEIAKKIKEEPSEERKEVLEKLLQKLELP----KKFTLPLDPRMEVKGLIVEKCKVMDSKKLPLWLV 77
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  967 FINANPMGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIHLHSG- 1045
Cdd:cd00891     78 FKNADPGGDPIKVIFKAGDDLRQDQLTLQLLRIMDKLWKKEGLDLRMTPYKCIATGDEVGMIEVVPNSETTAAIQKKYGg 157
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1046 LIGPLKENTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQTFGG 1125
Cdd:cd00891    158 FGAAFKDTPISNWLKKHNPTEEEYEEAVENFIRSCAGYCVATYVLGIGDRHNDNIMVTKSGHLFHIDFGHFLGNFKKKFG 237
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1126 IKRDRAPFIFTSEMEYFIteGGKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDLKYVHNNLRPQ 1205
Cdd:cd00891    238 IKRERAPFVFTPEMAYVM--GGEDSENFQKFEDLCCKAYNILRKHGNLLINLFSLMLSAGIPELQSIEDIEYLRDALQLD 315
                          330
                   ....*....|....*...
gi 1340723175 1206 DTDLEATSHFTKKIKESL 1223
Cdd:cd00891    316 LSDEEAAEHFRKLIHESL 333
PI3Kc_C2_alpha cd05176
Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
887-1239 5.58e-151

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  Cd Length: 353  Bit Score: 463.30  E-value: 5.58e-151
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  887 EELSKEQKLVKLLGDIGEKVKSASDPQRKDVLKKEIGSLEEFFKDIKtCHLPLNPALCIKGIDRDACSYFTSNASPLKIT 966
Cdd:cd05176      2 EELEKQTRLVQLLGRVAEKVRQASGSARQVALQDGMERVQSFFQKNK-CRLPLSPSLVAKELNIKACSFFSSNAVPLKVA 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  967 FINANPMGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIHLHSGL 1046
Cdd:cd05176     81 LVNADPLGEEINVMFKVGEDLRQDMLALQMIKIMDKIWLQEGLDLRMVIFKCLSTGKDRGMVELVPSSDTLRKIQVEYGV 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1047 IGPLKENTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQTFGGI 1126
Cdd:cd05176    161 TGSFKDKPLAEWLRKYNPSEEEYEKASENFIYSCAGCCVATYVLGICDRHNDNIMLRSTGHMFHIDFGKFLGHAQMFGSF 240
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1127 KRDRAPFIFTSEMEYFITEGGKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDLKYVHNNLRPQD 1206
Cdd:cd05176    241 KRDRAPFVLTSDMAYVINGGEKPTIRFQLFVDLCCQAYNLIRKHTNLFLNLLSLMLSSGLPELTGIQDLKYVFDALQPQT 320
                          330       340       350
                   ....*....|....*....|....*....|...
gi 1340723175 1207 TDLEATSHFTKKIKESLECFPVKLNNLIHTLAQ 1239
Cdd:cd05176    321 TDAEATIFFTRLIESSLGSVATKFNFFIHNLAQ 353
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
887-1239 2.84e-140

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: 434.81  E-value: 2.84e-140
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  887 EELSKEQKLVKLLGDIGEKVKSASDPQRKDVLKKEIGSLEEFFKDIKTCHLPLNPALCIKGIDRDACSYFTSNASPLKIT 966
Cdd:cd00895      2 EEFDRQCWLVNVLAKLAQQVREAAPSARQGILREGLEEVKQFFSINGSCRLPLSPSLLVKGIVPRDCSYFNSNAVPLKLS 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  967 FINANPMGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIHLHSGL 1046
Cdd:cd00895     82 FQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMNKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEHGV 161
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1047 IGPLKENTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQTFGGI 1126
Cdd:cd00895    162 TGSFKDRPLADWLQKHNPTEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGNI 241
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1127 KRDRAPFIFTSEMEYFITEGGKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDLKYVHNNLRPQD 1206
Cdd:cd00895    242 KRDRAPFVFTSDMAYVINGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQD 321
                          330       340       350
                   ....*....|....*....|....*....|...
gi 1340723175 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 ...
883-1239 9.45e-117

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  Cd Length: 363  Bit Score: 371.20  E-value: 9.45e-117
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  883 EALNeelskeqKLVKLLGDIgeKVKSASDPQRKDVLKKEIgSLEEFFKDIKTCHLPLNPALCIKGIDRDACSYFTSNASP 962
Cdd:cd05165      9 EALN-------KLKKLSDIL--KEKKKSKEKVKKLLKECL-KQKFYDEALQNFQSPLNPSHKLGELIIEKCKVMDSKKRP 78
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  963 LKITFINANPM---GKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAK 1039
Cdd:cd05165     79 LWLVFENADPLalsGEDIKIIFKNGDDLRQDMLTLQIIRIMDNIWKEEGLDLRMLPYGCLSTGDNVGLIEVVRNAKTIAN 158
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1040 IHLHSGL--IGPLKENTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFL 1117
Cdd:cd05165    159 IQKKKGKvaTLAFNKDSLHKWLKEKNKTGEKYDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVKENGQLFHIDFGHFL 238
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1118 GHAQTFGGIKRDRAPFIFTSEMEYFITEGGK--NTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDL 1195
Cdd:cd05165    239 GNFKKKFGIKRERVPFVLTHDFVYVIARGQDntKSEEFQEFQELCEKAYLILRRHGNLFISLFSMMLSTGIPELTSVKDI 318
                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*
gi 1340723175 1196 KYVHNNLRPQDTDLEATSHFTKKIKESL-ECFPVKLNNLIHTLAQ 1239
Cdd:cd05165    319 EYLRKTLALDKTEEEALKYFRKKFNEALkGSWTTKVNWFFHNVKH 363
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
887-1239 5.39e-91

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: 299.06  E-value: 5.39e-91
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  887 EELSKEQKLVKLLGDIGEKVKSASDPQRKDV--LKKEIGSLEEF-FKDIKTCHLPLNPALCIKGIDRDACSYFTSNASPL 963
Cdd:cd00896      2 EALKRQQEFVDRLRSLMKEVKNEKGSRDKKIerLRELLSDSELGlLLFFEPLPLPLDPSVKVTGIIPEKSTVFKSALMPL 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  964 KITFINANpmGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIhLH 1043
Cdd:cd00896     82 KLTFKTLD--GGEYKVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVPNSKALADI-LK 158
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1044 sgligplKENTIKKWFSQHNHLKED----YEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGh 1119
Cdd:cd00896    159 -------KYGSILNFLRKHNPDESGpygiKPEVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHIDFGYILG- 230
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1120 aqtfggikRD----RAPFIFTSEMeyfiTE--GGKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIE 1193
Cdd:cd00896    231 --------RDpkpfPPPMKLCKEM----VEamGGANSEGYKEFKKYCCTAYNILRKHANLILNLFSLMVDANIPDIALEP 298
                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*....
gi 1340723175 1194 D--LKYVHNNLRPQDTDLEATSHFTKKIKESL-ECFPVkLNNLIHTLAQ 1239
Cdd:cd00896    299 DkaVLKVQEKFRLDLSDEEAEQYFQNLIDESVnALFPA-VVETIHKIAQ 346
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
886-1239 8.84e-85

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  Cd Length: 366  Bit Score: 282.32  E-value: 8.84e-85
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  886 NEELSKEQKLVKLLGDIGEKvksASDPQRKDVLKKEIGSlEEFFKDIKTCHLPLNPALCIKGIDRDACSYFTSNASPLKI 965
Cdd:cd05174     11 GEALSKMKALNDFVKVSSQK---ATKPQTKEMMHVCMKQ-ETYMEALSHLQSPLDPSIILEEVCVDQCTFMDSKMKPLWI 86
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  966 TFINANPMGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIHL--- 1042
Cdd:cd05174     87 MYSSEEAGAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDTIANIQLnks 166
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1043 HSGLIGPLKENTIKKWFSQHNHlKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQT 1122
Cdd:cd05174    167 NMAATAAFNKDALLNWLKSKNP-GDALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFGHFLGNFKT 245
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1123 FGGIKRDRAPFIFTSEMEYFITEG-GKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDLKYVHNN 1201
Cdd:cd05174    246 KFGINRERVPFILTYDFVHVIQQGkTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCSKDIQYLKDS 325
                          330       340       350
                   ....*....|....*....|....*....|....*....
gi 1340723175 1202 LRPQDTDLEATSHFTKKIKESL-ECFPVKLNNLIHTLAQ 1239
Cdd:cd05174    326 LALGKTEEEALKHFRVKFNEALrESWKTKVNWLAHNVSK 364
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
936-1239 1.71e-82

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: 275.69  E-value: 1.71e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  936 HLPLNPALCIKGIDRDACSYFTSNASPLKITFINANPMGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMIT 1015
Cdd:cd05173     54 QSPLNPSIILSELNVEKCKYMDSKMKPLWIVYNNKLFGGDSLGIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVP 133
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1016 YGCLSTGRAQGFIEMVPDAVTLAKIHLHSGLI---GPLKENTIKKWFSQHNhLKEDYEKALRNFFYSCAGWCVVTFILGV 1092
Cdd:cd05173    134 YGCLATGDRSGLIEVVSSAETIADIQLNSSNVaaaAAFNKDALLNWLKEYN-SGDDLERAIEEFTLSCAGYCVATYVLGI 212
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1093 CDRHNDNIMLTKSGHMFHIDFGKFLGHAQTFGGIKRDRAPFIFTSEMEYFITEGGK-NTQHFQDFVELCCRAYNIVRKHS 1171
Cdd:cd05173    213 GDRHSDNIMVRKNGQLFHIDFGHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTgNTEKFGRFRQYCEDAYLILRKNG 292
                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1340723175 1172 QLILSLLEMMLHAGLPELRGIEDLKYVHNNLRPQDTDLEATSHFTKKIKESL-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 4.85e-78

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  Cd Length: 367  Bit Score: 262.88  E-value: 4.85e-78
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  887 EELSKEQKLVKLLGDIGEKVKSASdPQRKDVLKKEIGSLEEFFKDIKTCHLP------LNPALCIKGIDRDACSYFTSNA 960
Cdd:cd00894      2 HDFTQQVQVIEMLQKVTLDIKSLS-AEKYDVSSQVISQLKQKLENLQNSQLPesfrvpYDPGLRAGALVIEKCKVMASKK 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  961 SPLKITFINANPMG---KNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTL 1037
Cdd:cd00894     81 KPLWLEFKCADPTAlsnETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTI 160
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1038 AKIHLHS-GLIGPLKENTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKF 1116
Cdd:cd00894    161 AKIQQSTvGNTGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHI 240
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1117 LGHAQTFGGIKRDRAPFIFTSEMEYFI-TEGGKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDL 1195
Cdd:cd00894    241 LGNYKSFLGINKERVPFVLTPDFLFVMgTSGKKTSLHFQKFQDVCVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDI 320
                          330       340
                   ....*....|....*....|....*
gi 1340723175 1196 KYVHNNLRPQDTDLEATSHFTKKIK 1220
Cdd:cd00894    321 EYIRDALTVGKSEEDAKKHFLDQIE 345
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
979-1193 3.60e-72

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: 241.05  E-value: 3.60e-72
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175   979 VIFKAGDDLRQDMLALQIIQVMDNAWLQE----GLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIHLHS---------- 1044
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYrkqkgkvldl 80
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  1045 ---------------GLIGPLKENTIKKWFSQHN-HLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHM 1108
Cdd:smart00146   81 rsqtatrlkklelflEATGKFPDPVLYDWFTKKFpDPSEDYFEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160
                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  1109 FHIDFGKFLGHAQTFGGIKrDRAPFIFTSEMEYFITEggknTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPE 1188
Cdd:smart00146  161 FHIDFGFILGNGPKLFGFP-ERVPFRLTPEMVDVMGD----SGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLPD 235

                    ....*
gi 1340723175  1189 LRGIE 1193
Cdd:smart00146  236 WRSGK 240
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
885-1239 7.00e-72

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  Cd Length: 370  Bit Score: 245.35  E-value: 7.00e-72
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  885 LNEELSKEQKLVKLLGDIGEKVKSASDPQRKDVLKKEIgSLEEFFKDIKTCHLPLNPALCIKGIDRDACSYFTSNASPLK 964
Cdd:cd05175      8 LSRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQM-RRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKRPLW 86
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  965 ITFINANPMG----KNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKI 1040
Cdd:cd05175     87 LNWENPDIMSellfQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHTIMQI 166
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1041 HLHSGLIGPLKEN--TIKKWFSQHNHlKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLG 1118
Cdd:cd05175    167 QCKGGLKGALQFNshTLHQWLKDKNK-GEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGHFLD 245
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1119 HAQTFGGIKRDRAPFIFTSEMEYFITEGGK---NTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDL 1195
Cdd:cd05175    246 HKKKKFGYKRERVPFVLTQDFLIVISKGAQectKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSFDDI 325
                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*
gi 1340723175 1196 KYVHNNLRPQDTDLEATSHFTKKIKESLE-CFPVKLNNLIHTLAQ 1239
Cdd:cd05175    326 AYIRKTLALDKTEQEALEYFMKQMNDAHHgGWTTKMDWIFHTIKQ 370
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
713-880 1.41e-70

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: 233.50  E-value: 1.41e-70
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  713 ECLKHIAKLSQKKSPLLLSEEKRRYLWFYRLYCNNENSSLPLVLGSAPGWDEETVSEMHAILRRWTFSHPWEALGLLTSR 792
Cdd:cd00869      2 ETQEKLLDLIQKQSTYTLSTEDKDLLWEKRLYCTNEPNALPLVLASAPSWDWANLMDVYQLLHQWAPLRPLIALELLLPK 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  793 FPDQDIREVAVQQLDTLLTDELLDCLPQLVQAVKFEWNLESPLVELLLRRSLQSIRVAHRLYWLLRDAQGEAYFKSWYQE 872
Cdd:cd00869     82 FPDQEVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALDDCYFSSAYQD 161

                   ....*...
gi 1340723175  873 LLAALQFC 880
Cdd:cd00869    162 LGAALRCQ 169
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
975-1224 1.30e-64

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  Cd Length: 307  Bit Score: 222.08  E-value: 1.30e-64
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  975 KNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKihlhsglIGPLKENT 1054
Cdd:cd05167     48 VWQAAIFKVGDDCRQDMLALQLISLFKNIFEEVGLDLYLFPYRVVATGPGCGVIEVIPNSKSRDQ-------IGRETDNG 120
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1055 IKKWFSQH--NHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGkFLGHAQTFGGIKRDRAP 1132
Cdd:cd05167    121 LYEYFLSKygDESTPAFQKARRNFIKSMAGYSLVSYLLQIKDRHNGNIMIDDDGHIIHIDFG-FIFEISPGGNLGFESAP 199
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1133 FIFTSEMEYFItEGGKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRG--IEDLKyvhNNLRPQDTDLE 1210
Cdd:cd05167    200 FKLTKEMVDLM-GGSMESEPFKWFVELCVRGYLAVRPYAEAIVSLVELMLDSGLPCFRGqtIKNLR---ERFALEMSERE 275
                          250
                   ....*....|....
gi 1340723175 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 ...
963-1223 8.04e-62

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: 213.28  E-value: 8.04e-62
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  963 LKITFINANPMG-KNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIH 1041
Cdd:cd00893     13 IREKSPYGNLKGwKLVSLIVKTGDDLKQEQLALQLISQFDQIFKEEGLPLWLRPYEILSLGPDSGIIEMIKNAVSIDSLK 92
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1042 LHSGLIGplKENTIKKWFsQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQ 1121
Cdd:cd00893     93 KKLDSFN--KFVSLSDFF-DDNFGDEAIQKARDNFLQSLVAYSLVCYFLQIKDRHNGNILLDKEGHIIHIDFGFFLSSHP 169
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1122 tfGGIKRDRAPFIFTSemEYFITEGGKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDLKYVHNN 1201
Cdd:cd00893    170 --GFYGFEGAPFKLSS--EYIEVLGGVDSELFKEFRKLFLKGFMALRKHSDKILSLVEMMYSGHGITCFGKKTIQQLKQR 245
                          250       260
                   ....*....|....*....|..
gi 1340723175 1202 LRPQDTDLEATSHFTKKIKESL 1223
Cdd:cd00893    246 FNPELTEGELEVYVLSLINKSL 267
PX_PI3K_C2_gamma cd06896
The phosphoinositide binding Phox Homology Domain of the Gamma Isoform of Class II ...
1268-1368 5.60e-61

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: 203.22  E-value: 5.60e-61
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1268 RVTILGFSKTHSNLYLMEVTCSDNRRSLTKKSFEQFYRLHSQMQKQFSSLALPEFPHWWHLPFTDSDHKRIRDLSHYVEQ 1347
Cdd:cd06896      1 RATILGFSKKSSNLYLVQVTQSCNLVSLTEKSFEQFSELHSQLQKQFPSLALPEFPHWWHLPFTDSDHKRVRDLNHYLEQ 80
                           90       100
                   ....*....|....*....|.
gi 1340723175 1348 VLRGSYEVANSDCVLSFFLSE 1368
Cdd:cd06896     81 LLSGSREVANSDCVLSFFLSE 101
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
977-1190 3.36e-59

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


Pssm-ID: 395364 [Multi-domain]  Cd Length: 241  Bit Score: 203.72  E-value: 3.36e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  977 ISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMI-TYGCLSTGRAQGFIEMVPDAVTLAKIHLHSG---------- 1045
Cdd:pfam00454    2 YGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLRRLkPYSVIPLGPKCGIIEWVPNSETLAYILDEYGengvpptamv 81
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1046 ------------------LIGPLKENTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIML-TKSG 1106
Cdd:pfam00454   82 kilhsalnypklklefesRISLPPKVGLLQWFVKKSPDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTTG 161
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1107 HMFHIDFGKFLGHAQTFGGIKrDRAPFIFTSEMEYFITEggknTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAGL 1186
Cdd:pfam00454  162 KLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAMGP----SGDEGLFRELCETAYEALRRNLNLLTNLLKLMVADGL 236

                   ....
gi 1340723175 1187 PELR 1190
Cdd:pfam00454  237 PDWS 240
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
977-1223 6.09e-53

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: 187.69  E-value: 6.09e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  977 ISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVTLAKIHLHSGLIGPLKENTIK 1056
Cdd:cd05168     31 RSVIVKSGDDLRQELLAMQLIKQFQRIFEEAGLPLWLRPYEILVTSSDSGLIETIPDTVSIDSLKKRFPNFTSLLDYFER 110
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1057 KwFSQHNhlKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGHMFHIDFGKFLGHAQtfGGIKRDRAPFIFT 1136
Cdd:cd05168    111 T-FGDPN--SERFKEAQRNFVESLAAYSLVCYLLQIKDRHNGNILLDSEGHIIHIDFGFMLSNSP--GGLGFETAPFKLT 185
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1137 SEMEYFIteGGKNTQHFQDFVELCCRAYNIVRKHSQLILSLLEMMLHAG-LPELRG-----IEDLKyvhNNLRPQDTDLE 1210
Cdd:cd05168    186 QEYVEVM--GGLESDMFRYFKTLMIQGFLALRKHADRIVLLVEIMQQGSkLPCFFGggeftIEQLR---ERFKLNLTEEE 260
                          250
                   ....*....|...
gi 1340723175 1211 ATSHFTKKIKESL 1223
Cdd:cd05168    261 CAQFVDSLIDKSL 273
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
538-698 1.48e-49

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: 173.31  E-value: 1.48e-49
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  538 HAGLQSHLSFTVCSLHNVPETWAHSYKAFSFSCWLTYAGKKLCQVKSCRPLPVTKSFSLLVNWNEIINFPLEIKSLPRES 617
Cdd:cd04012      3 ASTVTDLLSVTVSSLHRIPPTWVQSFEDFYLSCSLYHGGRLLCSPVTTKPVKITKSFFPRVVWDEWIEFPIPVCQLPRES 82
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  618 MLIIKLFGIDSA--------THSTNLLAWTCLPLFP-RQESVLGSRLFSVTLQSEPPIEMIAPgVWDGSQPSPLTLQIDF 688
Cdd:cd04012     83 RLVLTLYGTTSSpdggsnkqRMGPEELGWVSLPLFDfRGVLRQGSLLLGLWPPSKDNPLGPAP-PPLFEQPDRVILQIDF 161
                          170
                   ....*....|
gi 1340723175  689 PDAGWEYLKP 698
Cdd:cd04012    162 PSSAFDVIFP 171
PI3Ka cd00864
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
712-858 1.04e-40

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: 147.36  E-value: 1.04e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  712 RECLKHIAKLSQKKSPLLLSEEKRRYLWFYRLYCNNENSSLPLVLGSAPGWDEETVSEMHAILRRWTFSHPWEALGLLTS 791
Cdd:cd00864      1 AWERKPLLAILLYPPFSTLTEEEKELLWKFRYYLLNVPKALPKLLKSVNWNDDEEVSELYQLLKWWAPLSPEDALELLSP 80
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1340723175  792 RFPDQDIREVAVQQLDTLLTDELLDCLPQLVQAVKFEWNLESPLVELLLRRSLQSIRVAHRLYWLLR 858
Cdd:cd00864     81 KYPDPVVRQYAVRVLESASDDELLLYLPQLVQALKYEPYLDSYLARFLLERALKSQRLGHQLYWNLK 147
C2B_PI3K_class_II cd08381
C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are ...
1390-1502 1.18e-39

C2 domain second 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. 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 second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176027 [Multi-domain]  Cd Length: 122  Bit Score: 143.20  E-value: 1.18e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1390 SPKVQLLMTYEDSRLTILVKHLKNIHLPDGSVPSAHVEIYLLPHPSEVRRKKTKCVPKCTDPTYNEIVVYDE--VLGLQG 1467
Cdd:cd08381      1 GGQVKLSISYKNGTLFVMVMHAKNLPLLDGSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDGlpVEDLQQ 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1340723175 1468 HVLMLIVKSKTVFVgaVNIQLCSVPLN---------EEKWYPLG 1502
Cdd:cd08381     81 RVLQVSVWSHDSLV--ENEFLGGVCIPlkkldlsqeTEKWYPLG 122
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
937-1221 8.52e-39

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 159.18  E-value: 8.52e-39
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  937 LPLNPALCIKGIDRDACSYFTSNASPLKITFINANpmGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGL----DMQ 1012
Cdd:COG5032   1759 LLDKPFVLIERFEPEVSVVKSHLQRPRRLTIRGSD--GKLYSFIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLW 1836
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1013 MITYGCLSTGRAQGFIEMVPDAVTLAKIHL---------------------HSGLIGPLK---------ENTIKKWFSQH 1062
Cdd:COG5032   1837 IRPYKVIPLSPGSGIIEWVPNSDTLHSILReyhkrknisidqekklaarldNLKLLLKDEfftkatlksPPVLYDWFSES 1916
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1063 NHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTK-SGHMFHIDFGKFLGHAQTFGGIKrDRAPFIFTSEMEY 1141
Cdd:COG5032   1917 FPNPEDWLTARTNFARSLAVYSVIGYILGLGDRHPGNILIDRsSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVE 1995
                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1142 FIteGGKNTQHFqdFVELCCRAYNIVRKHSQLILSLLEMMLHAGLPELRGIEDLKYVHNNLRPQDTDLeatshFTKKIKE 1221
Cdd:COG5032   1996 AM--GVSGVEGS--FRELCETAFRALRKNADSLMNVLELFVRDPLIEWRRLPCFREIQNNEIVNVLER-----FRLKLSE 2066
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
948-1182 1.22e-38

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: 144.01  E-value: 1.22e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  948 IDRDACSYFTSNASPLKITFINANpmGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQEGLDMQMITYGCLSTGRAQGF 1027
Cdd:cd00142      3 LDVGILKVIHSKQRPKKITLIGAD--GKTYSFLLKRRDDLRKDERSFQFMRLIQSILEKESVNLVLPPYKVIPLSENSGL 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1028 IEMVPDAVTLAkihlhsgligplkenTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDNIMLTKSGH 1107
Cdd:cd00142     81 IEIVKDAQTIE---------------DLLKSLWRKSPSSQSWLNRRENFSCSLAGYSVLGYIFGIGDRHPSNIMIEPSGN 145
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1340723175 1108 MFHIDFGKFLGHAQTFggIKRDRAPFIFTSEMEYFITEGGkntqHFQDFVELCCRAYNIVRKHSQLILSLLEMML 1182
Cdd:cd00142    146 IFHIDFGFIFSGRKLA--EGVETVPFRLTPMLENAMGTAG----VNGPFQISMVKIMEILREHADLIVPILEHSL 214
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
711-877 6.21e-28

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: 111.97  E-value: 6.21e-28
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175   711 PRECLKHIAKlsqKKSPLLLSEEKRRYLWFYRLYC-NNENSSLPLVLGSAPGWDEETVSEMHAILRRWTFSHPWEALGLL 789
Cdd:smart00145    7 EREQLEAILK---LDPTYELTEEEKDLIWKFRHYYlTNNPKALPKFLLSVKWSDADEVAQALSLLLSWAPLDPEDALELL 83
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175   790 TSRFPDQDIREVAVQQLDTLLTDELLDCLPQLVQAVKFEWNLESPLVELLLRRSLQSIRVAHRLYWLLRDAQGEAYFKSW 869
Cdd:smart00145   84 DPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHVSIR 163

                    ....*...
gi 1340723175   870 YQELLAAL 877
Cdd:smart00145  164 FGLLLEAY 171
PX_PI3K_C2 cd06883
The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases; The ...
1269-1368 8.02e-28

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: 108.98  E-value: 8.02e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1269 VTILGFSKTHS----NLYLMEVTCSD-NRRSLTKKSFEQFYRLHSQMQKQFSSLALPEFPHWWHLPFT---DSDHKRIRD 1340
Cdd:cd06883      2 VSVFGFQKRYSpekyYIYVVKVTRENqTEPSFVFRTFEEFQELHNKLSLLFPSLKLPSFPARVVLGRShikQVAERRKIE 81
                           90       100
                   ....*....|....*....|....*...
gi 1340723175 1341 LSHYVEQVLRGSYEVANSDCVLSFFLSE 1368
Cdd:cd06883     82 LNSYLKSLFNASPEVAESDLVYTFFHPL 109
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
724-858 1.09e-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: 99.71  E-value: 1.09e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  724 KKSPLL-LSEEKRRYLWFYRLYCNNENSSLPLVLGSAPGWDEETVSEMHAILRRWTFSHPWEALGLLTSRFPDQDIREVA 802
Cdd:pfam00613   18 AYDPLSkLTAEEKDLIWKFRYYLMLVPKALTKLLLSVKWSDLSEVAEALSLLLKWAPIDPVDALELLDPKFPDPEVRQYA 97
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1340723175  803 VQQLDTLLTDELLDCLPQLVQAVKFEWNLESPLVELLLRRSLQSIRVAHRLYWLLR 858
Cdd:pfam00613   98 VKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLK 153
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
730-858 7.87e-23

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: 97.00  E-value: 7.87e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  730 LSEEKRRYLWFYRLYCNNENSSLPLVLGSAPGWDEETVSEMHAILRRWTFSHPWEALGLLTSRFPDQDIREVAVQQLDTL 809
Cdd:cd00872     19 LTEEDKELLWKLRHECRKKPQALPKLLLSVKWNKRDDVAQMYQLLKRWPKLKPEQALELLDCNFPDEHVREFAVRCLEKL 98
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*....
gi 1340723175  810 LTDELLDCLPQLVQAVKFEWNLESPLVELLLRRSLQSIRVAHRLYWLLR 858
Cdd:cd00872     99 SDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLR 147
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
945-1183 1.32e-20

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: 91.95  E-value: 1.32e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  945 IKGIDrDACSYFTSNASPLKITFINANpmGKNISVIFKAGDDLRQDMLALQIIQVMdNAWLQ-----EGLDMQMITYGCL 1019
Cdd:cd05164      1 IASFD-PRVRILASLQKPKKITILGSD--GKEYPFLVKGDDDLRKDERVMQLFQLL-NTLLEkdketRKRNLTIRTYSVV 76
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1020 STGRAQGFIEMVPDAVTLakihlhsgligplkENTIKKWFSQHNHLKEDYEKALRNFFYSCAGWCVVTFILGVCDRHNDN 1099
Cdd:cd05164     77 PLSSQSGLIEWVDNTTTL--------------KPVLKKWFNETFPDPTQWYEARSNYTKSTAVMSMVGYIIGLGDRHLEN 142
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1100 IML-TKSGHMFHIDFGKFLGHAQTFGgiKRDRAPFIFTSEMEYFITEGGKNTQhFQDFVELCCRAYnivRKHSQLILSLL 1178
Cdd:cd05164    143 ILIdTKTGEVVHIDFGMIFNKGKTLP--VPEIVPFRLTRNIINGMGPTGVEGL-FRKSCEQVLRVF---RKHKDKLITFL 216

                   ....*
gi 1340723175 1179 EMMLH 1183
Cdd:cd05164    217 DTFLY 221
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
962-1183 9.69e-18

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  Cd Length: 282  Bit Score: 85.28  E-value: 9.69e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  962 PLKITFINANpmGKNISVIFKAGDDLRQDMLALQIIQVMdNAWLQEGL-----DMQMITYGCLSTGRAQGFIEMVPDAVT 1036
Cdd:cd05171     17 PKIITCIGSD--GKKYKQLVKGGDDLRQDAVMEQVFELV-NQLLKRDKetrkrKLRIRTYKVVPLSPRSGVLEFVENTIP 93
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1037 LAKI----HLHSGL-----IGPLKENTIKKWFSQHNHLKED-----YEK-------ALRNFFY----------------- 1078
Cdd:cd05171     94 LGEYlvgaSSKSGAharyrPKDWTASTCRKKMREKAKASAEerlkvFDEicknfkpVFRHFFLekfpdpsdwferrlayt 173
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1079 -SCAGWCVVTFILGVCDRHNDNIML-TKSGHMFHIDFGkflghaQTFGGIKR----DRAPFIFTSE----MEYFITEGgk 1148
Cdd:cd05171    174 rSVATSSIVGYILGLGDRHLNNILIdQKTGELVHIDLG------IAFEQGKLlpipETVPFRLTRDivdgMGITGVEG-- 245
                          250       260       270
                   ....*....|....*....|....*....|....*
gi 1340723175 1149 ntqhfqDFVELCCRAYNIVRKHSQLILSLLEMMLH 1183
Cdd:cd05171    246 ------VFRRCCEETLRVLRENKEALLTILEVLLY 274
PX smart00312
PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function ...
1274-1365 3.99e-16

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: 75.46  E-value: 3.99e-16
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  1274 FSKTHSNLYLMEVTCSDN-RRSLTKKSFEQFYRLHSQMQKQFSSLALPEFPHWWHLPFTDSD-----HKRIRDLSHYVEQ 1347
Cdd:smart00312    7 IGDGKHYYYVIEIETKTGlEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRLNNFseefiEKRRRGLEKYLQS 86
                            90
                    ....*....|....*...
gi 1340723175  1348 VLRGSYEVANSDCVLSFF 1365
Cdd:smart00312   87 LLNHPELINHSEVVLEFL 104
PIKKc_DNA-PK cd05172
Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, ...
956-1179 7.01e-16

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: 78.77  E-value: 7.01e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  956 FTSNASPLKITFINANpmGKNISVIFKAGDDLRQDMLALQIIQVMDNAWLQE----GLDMQMITYGCLSTGRAQGFIEMV 1031
Cdd:cd05172     11 LSSKRRPKRITIRGSD--EKEYKFLVKGGEDLRQDQRIQQLFDVMNNILASDpacrQRRLRIRTYQVIPMTSRLGLIEWV 88
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1032 PDAVTLAKIhlhsgligpLKENTIKKWFSQHNHLKEDYeKALR-NFFYSCAGWCVVTFILGVCDRHNDNIML-TKSGHMF 1109
Cdd:cd05172     89 DNTTPLKEI---------LENDLLRRALLSLASSPEAF-LALRsNFARSLAAMSICGYILGIGDRHLSNFLVdLSTGRLI 158
                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1110 HIDFGKFLGHAQTFGGIKrDRAPFIFTSEMEYFITEGGKNTQHFQDFVeLCCRAYnivRKHSQLILSLLE 1179
Cdd:cd05172    159 GIDFGHAFGSATQFLPIP-ELVPFRLTRQLLNLLQPLDARGLLRSDMV-HVLRAL---RAGRDLLLATMD 223
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
945-1183 3.10e-15

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: 76.78  E-value: 3.10e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  945 IKGIDRDAcSYFTSNASPLKITFINANpmGKNISVIFKAGDDLRQDMLALQIIQVM------DNAWLQEGLDMQmiTYGC 1018
Cdd:cd00892      1 ISGFEDEV-EIMPSLQKPKKITLVGSD--GKKYPFLCKPKDDLRKDARMMEFNTLInrllskDPESRRRNLHIR--TYAV 75
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1019 LSTGRAQGFIEMVPDAVTLAKIhlhsglIGPLKENTIKKWFsqHNHLKEDYE--KALRNFFYSCAGWCVVTFILGVCDRH 1096
Cdd:cd00892     76 IPLNEECGIIEWVPNTVTLRSI------LSTLYPPVLHEWF--LKNFPDPTAwyEARNNYTRSTAVMSMVGYILGLGDRH 147
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1097 NDNIML-TKSGHMFHIDFGKFLGHAQTFGgiKRDRAPFIFTSEMeyfI-------TEGGkntqhfqdFVELCCRAYNIVR 1168
Cdd:cd00892    148 GENILFdSTTGDVVHVDFDCLFDKGLTLE--VPERVPFRLTQNM---VdamgvtgVEGT--------FRRTCEVTLRVLR 214
                          250
                   ....*....|....*
gi 1340723175 1169 KHSQLILSLLEMMLH 1183
Cdd:cd00892    215 ENRETLMSVLETFVH 229
PI3Ka_III cd00870
Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is ...
730-857 3.21e-14

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: 71.98  E-value: 3.21e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  730 LSEEKRRYLWFYRLYCNNENSSLPLVLGSAPGWDEETVSEMHAILRRWTFSHPWEALGLLTSRFPDQDIREVAVQQLDTL 809
Cdd:cd00870     26 LTDEEKDLIWKFRFYLTNNKKALTKFLKSVNWSDEQEVKQALELMPKWAKIDIEDALELLSPYFTNPVVRKYAVSRLKLA 105
                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*
gi 1340723175  810 LTDELLDCLPQLVQAVKFE-------WNLESPLVELLLRRSLQSIRVAHRLYWLL 857
Cdd:cd00870    106 SDEELLLYLLQLVQALKYEnldlsplPRLDSPLADFLIERALKNPKLANFLYWYL 160
PX pfam00787
PX domain; PX domains bind to phosphoinositides.
1286-1368 4.79e-13

PX domain; PX domains bind to phosphoinositides.


Pssm-ID: 395635  Cd Length: 84  Bit Score: 65.73  E-value: 4.79e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1286 VTCSDNRRSLTKKSFEQFYRLHSQMQKQFSSLALPEFPHW-WHLPFTDSD-HKRIRDLSHYVEQVLRGSyEVANSDCVLS 1363
Cdd:pfam00787    1 LPTFDLEEWSVRRRYSDFVELHKQLLRKFPSLIIPPLPPKvWFGRYNEEFiEKRRKGLEQYLQRLLQHP-ELRNSEVLLE 79

                   ....*
gi 1340723175 1364 FFLSE 1368
Cdd:pfam00787   80 FLESD 84
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
1392-1501 8.68e-13

C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology and do not bind Ca2+.


Pssm-ID: 175997 [Multi-domain]  Cd Length: 125  Bit Score: 66.50  E-value: 8.68e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1392 KVQLLMTYEDSRLTILVKHLKNIHLP---DGSVPSAHVEIYLLPHPSEVRRKKTKCVPKCTDPTYNEIVVYDEVLG--LQ 1466
Cdd:cd04031      4 RIQIQLWYDKVTSQLIVTVLQARDLPprdDGSLRNPYVKVYLLPDRSEKSKRRTKTVKKTLNPEWNQTFEYSNVRRetLK 83
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1340723175 1467 GHVLMLIV----KSKT-VFVGAVNIQLCSVPLNEE-KWYPL 1501
Cdd:cd04031     84 ERTLEVTVwdydRDGEnDFLGEVVIDLADALLDDEpHWYPL 124
PX_domain cd06093
The Phox Homology domain, a phosphoinositide binding module; The PX domain is a ...
1269-1365 6.69e-11

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  Cd Length: 106  Bit Score: 60.45  E-value: 6.69e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1269 VTILGFSKTHSN-----LYLMEVTCSDNRRSLTKKSFEQFYRLHSQMQKQFSSLALPEFPHWWHLPFTDSD--HKRIRDL 1341
Cdd:cd06093      2 VSIPDYEKVKDGgkkyvVYIIEVTTQGGEEWTVYRRYSDFEELHEKLKKKFPGVILPPLPPKKLFGNLDPEfiEERRKQL 81
                           90       100
                   ....*....|....*....|....
gi 1340723175 1342 SHYVEQVLRgSYEVANSDCVLSFF 1365
Cdd:cd06093     82 EQYLQSLLN-HPELRNSEELKEFL 104
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
543-626 3.87e-10

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 58.13  E-value: 3.87e-10
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175   543 SHLSFTVCSLHNVPETWAHSYKAFSFSCWLTYAGKKLCQVKSCRPlpvtKSFSLLVNWNEIINFPLEIKSLPRESMLIIK 622
Cdd:smart00142   11 RNLVITIALIHGIPLNWSRDYSDLYVEIQLYHGGKLLCLPVSTSY----KPFFPSVKWNEWLTFPIQISDLPREARLCIT 86

                    ....
gi 1340723175   623 LFGI 626
Cdd:smart00142   87 IYAV 90
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
569-644 9.87e-10

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: 58.15  E-value: 9.87e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  569 SCWLTYAGKKLCqvkscrpLPVT---KSFS-LLVNWNEIINFPLEIKSLPRESMLIIKLFGIDSATHSTNLLAWTCLPLF 644
Cdd:pfam00792    8 ECQLYHGGKPLC-------LPVStryVPFSnSSIKWNEWITFPIQISDLPRSARLCITIWDVSGPEKSFVPIGWVNTSLF 80
C2 pfam00168
C2 domain;
1403-1501 4.64e-09

C2 domain;


Pssm-ID: 395116 [Multi-domain]  Cd Length: 104  Bit Score: 55.40  E-value: 4.64e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1403 RLTILVKHLKNIHLPDGSVPS-AHVEIYLLphpSEVRRKKTKCVPKCTDPTYNEIVVYdEVLGLQGHVLMLIVK-----S 1476
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDLNGKSdPYVKVSLL---DGKQKKKTKVVKNTLNPVWNETFTF-SVPDPENQVLEIEVYdydrfG 77
                           90       100
                   ....*....|....*....|....*..
gi 1340723175 1477 KTVFVGAVNIQLCSVPLNE--EKWYPL 1501
Cdd:pfam00168   78 RDDFLGEVRIPLSELLLGEglDGWYPL 104
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
956-1183 4.71e-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: 55.95  E-value: 4.71e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  956 FTSNASPLKITFINANpmGKNISVIFKAGDDLRQDMLALQ----IIQVMDNAWLQEGLDMQMITYGCLSTGRAQGFIEMV 1031
Cdd:cd05169     11 ITSKQRPRKLTIVGSD--GKEYKFLLKGHEDLRLDERVMQlfglVNTLLKNDSETSRRNLSIQRYSVIPLSPNSGLIGWV 88
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1032 PDAVTLAKI-----HLHSglIGPLKEN-TIKKWFSQHNHL-----KEDYEKALR-------------------------- 1074
Cdd:cd05169     89 PGCDTLHSLirdyrEKRK--IPLNIEHrLMLQMAPDYDNLtliqkVEVFEYALEntpgddlrrvlwlkspsseawlerrt 166
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1075 NFFYSCAGWCVVTFILGVCDRHNDNIML-TKSGHMFHIDFG----------KFlghaqtfggikRDRAPF----IFTSEM 1139
Cdd:cd05169    167 NFTRSLAVMSMVGYILGLGDRHPSNIMLdRLTGKVIHIDFGdcfevamhreKF-----------PEKVPFrltrMLVNAM 235
                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....
gi 1340723175 1140 EYFITEGgkntqhfqDFVELCCRAYNIVRKHSQLILSLLEMMLH 1183
Cdd:cd05169    236 EVSGVEG--------TFRSTCEDVMRVLRENKDSLMAVLEAFVH 271
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
974-1114 2.29e-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: 51.29  E-value: 2.29e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  974 GKNISVIFKAGDDlRQDMLALQIIQVMDNawLQEGLDMQMITYGCLSTGRAQGFIEMVPDAVtlakihlhSGliGPLKEN 1053
Cdd:cd13968     16 CTTIGVAVKIGDD-VNNEEGEDLESEMDI--LRRLKGLELNIPKVLVTEDVDGPNILLMELV--------KG--GTLIAY 82
                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1340723175 1054 TIKKwfsqhnhlkEDYEKALRNFFYSCAGWCVVTFILGVC--DRHNDNIMLTKSGHMFHIDFG 1114
Cdd:cd13968     83 TQEE---------ELDEKDVESIMYQLAECMRLLHSFHLIhrDLNNDNILLSEDGNVKLIDFG 136
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
1403-1498 3.10e-07

Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, protein kinases C, and synaptotagmins (among others). Some do not appear to contain Ca2+-binding sites. Particular C2s appear to bind phospholipids, inositol polyphosphates, and intracellular proteins. Unusual occurrence in perforin. Synaptotagmin and PLC C2s are permuted in sequence with respect to N- and C-terminal beta strands. SMART detects C2 domains using one or both of two profiles.


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 49.79  E-value: 3.10e-07
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  1403 RLTILVKHLKNI-HLPDGSVPSAHVEIYLLPHPSEVrrKKTKCVPKCTDPTYNEIVVYDeVLGLQGHVLMLIVKSKTV-- 1479
Cdd:smart00239    1 TLTVKIISARNLpPKDKGGKSDPYVKVSLDGDPKEK--KKTKVVKNTLNPVWNETFEFE-VPPPELAELEIEVYDKDRfg 77
                            90       100
                    ....*....|....*....|..
gi 1340723175  1480 ---FVGAVNIQLCSVPLNEEKW 1498
Cdd:smart00239   78 rddFIGQVTIPLSDLLLGGRHE 99
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
1391-1494 1.51e-06

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. There are several classes of Synaptotagmins. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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 second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175975 [Multi-domain]  Cd Length: 134  Bit Score: 48.73  E-value: 1.51e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1391 PKVQLLMTY--EDSRLTILVKHLKNIHLPDGSV-PSAHVEIYLLPHPSEVRRKKTKCVPKCTDPTYNEIVVYD-EVLGLQ 1466
Cdd:cd00276      1 GELLLSLSYlpTAERLTVVVLKARNLPPSDGKGlSDPYVKVSLLQGGKKLKKKKTSVKKGTLNPVFNEAFSFDvPAEQLE 80
                           90       100
                   ....*....|....*....|....*...
gi 1340723175 1467 GHVLMLIVKSKTVFVGAVNIQLCSVPLN 1494
Cdd:cd00276     81 EVSLVITVVDKDSVGRNEVIGQVVLGPD 108
PX_SNX27 cd06886
The phosphoinositide binding Phox Homology domain of Sorting Nexin 27; The PX domain is a ...
1293-1348 2.26e-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: 47.79  E-value: 2.26e-06
                           10        20        30        40        50
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1340723175 1293 RSLTKKSFEQFYRLHSQMQKQFSSLALPEFPHWWhlPFTDSDHK---RIRDLSHYVEQV 1348
Cdd:cd06886     31 RQLCSRRYREFANLHQNLKKEFPDFQFPKLPGKW--PFSLSEQQldaRRRGLEQYLEKV 87
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
962-1183 2.64e-06

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: 51.10  E-value: 2.64e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  962 PLKITFINANpmGKNISVIFKAGDDLRQD---MLALQIIQVM---DNAwlQEGLDMQMITYGCLSTGRAQGFIEMVPDAV 1035
Cdd:cd05170     17 PKKLVFLGSD--GKRYPYLFKGLEDLHLDeriMQFLSIVNAMlasDNE--HRRRRYRARHYSVTPLGPRSGLIQWVDGAT 92
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1036 TLAKIH-------------------------------LHSGLIGPLKENTIKK--------------------------- 1057
Cdd:cd05170     93 PLFSLYkrwqqrraaaqaqknqdsgstpppvprpselFYNKLKPALKAAGIRKstsrrewplevlrqvleelvaetprdl 172
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1058 -----WFSQHNhLKEDYEKaLRNFFYSCAGWCVVTFILGVCDRHNDNIMLT-KSGHMFHIDF------GKFLghaqtfgg 1125
Cdd:cd05170    173 larelWCSSPS-SAEWWRV-TQRFARSLAVMSMIGYIIGLGDRHLDNILVDlSTGEVVHIDYnvcfekGKRL-------- 242
                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1340723175 1126 ikR--DRAPFIFTSEMEYFI----TEGgkntqhfqDFVELCCRAYNIVRKHSQLILSLLEMMLH 1183
Cdd:cd05170    243 --RvpEKVPFRLTQNIEHALgptgVEG--------TFRLSCEQVLKILRKGRETLLTLLEAFVY 296
C2_PI3K_like cd08380
C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes ...
545-644 6.25e-06

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: 47.74  E-value: 6.25e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  545 LSFTVCSLHNVPETWAHSYKaFSFSCWLTYAGKKLCQVKSCRPLPvtksFSLLVNWNEIINFPLEIKSLPRESMLIIKLF 624
Cdd:cd08380     10 LRIKIHGITNINLLDSEDLK-LYVRVQLYHGGEPLCPPQSTKKVP----FSTSVTWNEWLTFDILISDLPREARLCLSIY 84
                           90       100
                   ....*....|....*....|.
gi 1340723175  625 GIDS-ATHSTNLLAWTCLPLF 644
Cdd:cd08380     85 AVSEpGSKKEVPLGWVNVPLF 105
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
1379-1462 7.50e-06

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. 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 second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175987 [Multi-domain]  Cd Length: 162  Bit Score: 47.70  E-value: 7.50e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1379 FVDPGENSLDKSPKVqllmtyEDSRLTILVKHLKNihLP----DGSVPSaHVEIYLLPHPSEVRRKKTKCVPKCTDPTYN 1454
Cdd:cd04020     10 YVPPESEGALKSKKP------STGELHVWVKEAKN--LPalksGGTSDS-FVKCYLLPDKSKKSKQKTPVVKKSVNPVWN 80

                   ....*...
gi 1340723175 1455 EIVVYDEV 1462
Cdd:cd04020     81 HTFVYDGV 88
C2B_RIM1alpha cd04028
C2 domain second repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
1392-1505 1.32e-05

C2 domain second repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are believed to organize specialized sites of the plasma membrane called active zones. They also play a role in controlling neurotransmitter release, plasticity processes, as well as memory and learning. RIM contains an N-terminal zinc finger domain, a PDZ domain, and two C-terminal C2 domains (C2A, C2B). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology and do not bind Ca2+.


Pssm-ID: 175994 [Multi-domain]  Cd Length: 146  Bit Score: 46.61  E-value: 1.32e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1392 KVQLLMTYEDSRLTILVKHLKN-IHLPDGSVPSA-HVEIYLLPHPSEVRRKKTKCVPKCTDPTYNEIVVYDEvlGLQGHV 1469
Cdd:cd04028     19 DIQLGLYDKKGQLEVEVIRARGlVQKPGSKVLPApYVKVYLLEGKKCIAKKKTKIARKTLDPLYQQQLVFDV--SPTGKT 96
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1340723175 1470 LMLIV------KSKTVFVGAVNIQLCSVPLNEE--KWYPLGNSI 1505
Cdd:cd04028     97 LQVIVwgdygrMDKKVFMGVAQILLDDLDLSNLviGWYKLFPTS 140
C2A_SLP-1_2 cd08393
C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members ...
1425-1501 1.35e-05

C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike Slp3 and Slp4/granuphilin which are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. 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: 176039 [Multi-domain]  Cd Length: 125  Bit Score: 45.89  E-value: 1.35e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1425 HVEIYLLPHPSEVRRKKTKCVPKCTDPTYNEIVVYD-EVLGLQGHVLMLIV-----KSKTVFVGAVNIQLCSVPLNEEK- 1497
Cdd:cd08393     40 YVKTYLLPDKSNRGKRKTSVKKKTLNPVFNETLRYKvEREELPTRVLNLSVwhrdsLGRNSFLGEVEVDLGSWDWSNTQp 119

                   ....*
gi 1340723175 1498 -WYPL 1501
Cdd:cd08393    120 tWYPL 124
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
1404-1501 1.63e-05

C2 domain; The C2 domain was first identified in PKC. 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.


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 45.14  E-value: 1.63e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1404 LTILVKHLKNIHLPD-GSVPSAHVEIYLLPHpsevRRKKTKCVPKCTDPTYNEIVVYdEVLGLQGHVLMLIVK-----SK 1477
Cdd:cd00030      1 LRVTVIEARNLPAKDlNGKSDPYVKVSLGGK----QKFKTKVVKNTLNPVWNETFEF-PVLDPESDTLTVEVWdkdrfSK 75
                           90       100
                   ....*....|....*....|....*..
gi 1340723175 1478 TVFVGAVNIQLCSV---PLNEEKWYPL 1501
Cdd:cd00030     76 DDFLGEVEIPLSELldsGKEGELWLPL 102
C2C_KIAA1228 cd04030
C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins ...
1392-1501 1.86e-05

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. 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 third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175996 [Multi-domain]  Cd Length: 127  Bit Score: 45.73  E-value: 1.86e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1392 KVQLLMTY--EDSRLTILVKHLKNIHLPDGS-VPSAHVEIYLLPHPSEVRRKKTKCVPKCTDPTYNEIVVYDEVLG-LQG 1467
Cdd:cd04030      4 RIQLTIRYssQRQKLIVTVHKCRNLPPCDSSdIPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFPVSLEeLKR 83
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1340723175 1468 HVLMLIVKSK-------TVFVGAVNIQLCSVPLNE--EKWYPL 1501
Cdd:cd04030     84 RTLDVAVKNSksflsreKKLLGQVLIDLSDLDLSKgfTQWYDL 126
PX_NoxO1 cd06889
The phosphoinositide binding Phox Homology domain of Nox Organizing protein 1; The PX domain ...
1279-1366 3.59e-05

The phosphoinositide binding Phox Homology domain of Nox Organizing protein 1; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Nox Organizing protein 1 (NoxO1) is a critical regulator of enzyme kinetics of the nonphagocytic NADPH oxidase Nox1, which catalyzes the transfer of electrons from NADPH to molecular oxygen to form superoxide. Nox1 is expressed in colon, stomach, uterus, prostate, and vascular smooth muscle cells. NoxO1, a homolog of the p47phox subunit of phagocytic NADPH oxidase, is involved in targeting activator subunits (such as NoxA1) to Nox1. It is co-localized with Nox1 in the membranes of resting cells and directs the subcellular localization of Nox1. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. The PX domain of NoxO1 preferentially binds phosphatidylinositol-3,5-bisphosphate [PI(3,5)P2], PI5P, and PI4P.


Pssm-ID: 132799  Cd Length: 121  Bit Score: 44.69  E-value: 3.59e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1279 SNLYLMEVTCSDNRRSLTKKSFEQFYRLHSQMQKQF---------SSLALPEFPHWWHLPF----TDSDHKRIRDLSHYV 1345
Cdd:cd06889     19 HKTYMFSVLWSDGSELFVYRSLEEFRKLHKQLKEKFpveagllrsSDRVLPKFKDAPSLGSlkgsTSRSLARLKLLETYC 98
                           90       100
                   ....*....|....*....|.
gi 1340723175 1346 EQVLRGSYEVANSDCVLSFFL 1366
Cdd:cd06889     99 QELLRLDEKVSRSPEVIQFFA 119
PX_PI3K_C2_beta cd07290
The phosphoinositide binding Phox Homology Domain of the Beta Isoform of Class II ...
1297-1365 1.32e-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: 42.60  E-value: 1.32e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1340723175 1297 KKSFEQFYRLHSQMQKQFSSLALPEFPHWWHLPFTDSD---HKRIRDLSHYVEQVLRGSYEVANSDCVLSFF 1365
Cdd:cd07290     35 QRTFEEFQELHNKLRLLFPSSKLPSFPSRFVIGRSRGEavaERRKEELNGYIWHLIHAPPEVAECDLVYTFF 106
PX_PI3K_C2_alpha cd07289
The phosphoinositide binding Phox Homology Domain of the Alpha Isoform of Class II ...
1298-1365 1.58e-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: 42.61  E-value: 1.58e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1340723175 1298 KSFEQFYRLHSQMQKQFSSLALPEFPHWWHLPFT---DSDHKRIRDLSHYVEQVLRGSYEVANSDCVLSFF 1365
Cdd:cd07289     36 RTFDEFQELHNKLSILFPLWKLPGFPNKMVLGRThikDVAAKRKVELNSYIQSLMNSSTEVAECDLVYTFF 106
PX_SNX17_31 cd06885
The phosphoinositide binding Phox Homology domain of Sorting Nexins 17 and 31; The PX domain ...
1300-1367 4.85e-04

The phosphoinositide binding Phox Homology domain of Sorting Nexins 17 and 31; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Members of this subfamily include sorting nexin 17 (SNX17), SNX31, and similar proteins. They contain an N-terminal PX domain followed by a truncated FERM (4.1, ezrin, radixin, and moesin) domain and a unique C-terminal region. 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. SNX17 is known to regulate the trafficking and processing of a number of proteins. It binds some members of the low-density lipoprotein receptor (LDLR) family such as LDLR, VLDLR, ApoER2, and others, regulating their endocytosis. It also binds P-selectin and may regulate its lysosomal degradation. SNX17 is highly expressed in neurons. It binds amyloid precursor protein (APP) and may be involved in its intracellular trafficking and processing to amyloid beta peptide, which plays a central role in the pathogenesis of Alzheimer's disease. The biological function of SNX31 is unknown.


Pssm-ID: 132795  Cd Length: 104  Bit Score: 40.78  E-value: 4.85e-04
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1340723175 1300 FEQFYRLHSQMQKQFSSLALPEFPHWWHLPFTDSDHKRIRD-LSHYVeQVLRGSYEVANSDCVLSFFLS 1367
Cdd:cd06885     35 YSQLHGLNEQLKKEFGNRKLPPFPPKKLLPLTPAQLEERRLqLEKYL-QAVVQDPRIANSDIFNSFLLN 102
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
1392-1460 6.88e-04

C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha and gamma. The PKC family of serine/threonine kinases regulates apoptosis, proliferation, migration, motility, chemo-resistance, and differentiation. There are 3 groups: group 1(alpha, betaI, beta II, gamma) which require phospholipids and calcium, group 2 (delta, epsilon, theta, eta) which do not require calcium for activation, and group 3 (xi, iota/lambda) which are atypical and can be activated in the absence of diacylglycerol and calcium. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 175992 [Multi-domain]  Cd Length: 131  Bit Score: 41.09  E-value: 6.88e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1340723175 1392 KVQLLMTYEDSRLTILVKHLKNihL----PDG-SVPsaHVEIYLLPHPSEVRRKKTKCVPKCTDPTYNEIVVYD 1460
Cdd:cd04026      3 RIYLKISVKDNKLTVEVREAKN--LipmdPNGlSDP--YVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTFD 72
C2A_SLP cd08521
C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share ...
1393-1501 7.31e-04

C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. 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: 176056 [Multi-domain]  Cd Length: 123  Bit Score: 41.09  E-value: 7.31e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1393 VQLLMTYED--SRLTILVKHLKNIHLPDGS--VPSAHVEIYLLPHPSEVRRKKTKCVPKCTDPTYNEIVVY----DEvlg 1464
Cdd:cd08521      3 IEFSLSYNYktGSLEVHIKECRNLAYADEKkkRSNPYVKVYLLPDKSKQSKRKTSVKKNTTNPVFNETLKYhiskSQ--- 79
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1340723175 1465 LQGHVLMLIV-----KSKTVFVGAVNIQLCSVPLN--EEKWYPL 1501
Cdd:cd08521     80 LETRTLQLSVwhhdrFGRNTFLGEVEIPLDSWDLDsqQSEWYPL 123
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
1426-1499 1.35e-03

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). 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: 176000 [Multi-domain]  Cd Length: 123  Bit Score: 39.96  E-value: 1.35e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1426 VEIYLLPHPSEVRRKKTKCVPKCTDPTYNEIVVYDEVLG--LQGHVLMLIV----KSKTVFVGAVNIQLCSVPLNEEKWY 1499
Cdd:cd04035     40 VKLNLLPGASKATKLRTKTVHKTRNPEFNETLTYYGITEedIQRKTLRLLVldedRFGNDFLGETRIPLKKLKPNQTKQF 119
C2B_Synaptotagmin-15 cd08409
C2 domain second repeat present in Synaptotagmin 15; Synaptotagmin is a membrane-trafficking ...
1393-1455 1.46e-03

C2 domain second repeat present in Synaptotagmin 15; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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 second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176054  Cd Length: 137  Bit Score: 40.40  E-value: 1.46e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1340723175 1393 VQLLMTYED--SRLTILVKHLKNIHLPDGSVPSAHVEIYLLPHPSEVRRKKTKCVPKCTDPTYNE 1455
Cdd:cd08409      4 IQISLTYNPtlNRLTVVVLRARGLRQLDHAHTSVYVKVSLMIHNKVVKTKKTEVVDGAASPSFNE 68
C2_PI3K_class_III cd08397
C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
588-644 3.54e-03

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


Pssm-ID: 176042  Cd Length: 159  Bit Score: 39.54  E-value: 3.54e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175  588 LPVT---KSFSLLVNWNEIINFPLEIKSLPRESMLIIKLFGIDSATHSTnLLAWTCLPLF 644
Cdd:cd08397     47 LPVQtsyKPFKNRRNWNEWLTLPIKYSDLPRNSQLAITIWDVSGTGKAV-PFGGTTLSLF 105
C2B_Synaptotagmin-4 cd08404
C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...
1403-1460 4.15e-03

C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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 second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176049 [Multi-domain]  Cd Length: 136  Bit Score: 38.95  E-value: 4.15e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1340723175 1403 RLTILVkhLKNIHLP--DGSVPS-AHVEIYLLPHPSEVRRKKTKcVPKCT-DPTYNEIVVYD 1460
Cdd:cd08404     16 RLTVVV--LKARHLPkmDVSGLAdPYVKVNLYYGKKRISKKKTH-VKKCTlNPVFNESFVFD 74
C2A_SLP-4_5 cd04029
C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members ...
1390-1501 5.89e-03

C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp4/granuphilin promotes dense-core vesicle exocytosis. The C2A domain of Slp4 is Ca2+ dependent. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. 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: 175995 [Multi-domain]  Cd Length: 125  Bit Score: 38.19  E-value: 5.89e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1390 SPKVQLLMTYEDSR--LTILVKHLKNIHLPDGS--VPSAHVEIYLLPHPSEVRRKKTKCVPKCTDPTYNEIVVYD----- 1460
Cdd:cd04029      1 SGEILFSLSYDYKTqsLNVHVKECRNLAYGDEAkkRSNPYVKTYLLPDKSRQSKRKTSIKRNTTNPVYNETLKYSishsq 80
                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1340723175 1461 -EVLGLQGHVLMLIVKSKTVFVGAVNIQLCSVPLN--EEKWYPL 1501
Cdd:cd04029     81 lETRTLQLSVWHYDRFGRNTFLGEVEIPLDSWNFDsqHEECLPL 124
PX_Bem1p cd06890
The phosphoinositide binding Phox Homology domain of Bem1p; The PX domain is a ...
1282-1365 6.45e-03

The phosphoinositide binding Phox Homology domain of Bem1p; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Members of this subfamily bear similarity to Saccharomyces cerevisiae Bem1p, containing two Src Homology 3 (SH3) domains at the N-terminus, a central PX domain, and a C-terminal PB1 domain. Bem1p is a scaffolding protein that is critical for proper Cdc42p activation during bud formation in yeast. During budding and mating, Bem1p migrates to the plasma membrane where it can serve as an adaptor for Cdc42p and some other proteins. Bem1p also functions as an effector of the G1 cyclin Cln3p and the cyclin-dependent kinase Cdc28p in promoting vacuolar fusion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction. The PX domain of Bem1p specifically binds phosphatidylinositol-4-phosphate (PI4P).


Pssm-ID: 132800  Cd Length: 112  Bit Score: 38.04  E-value: 6.45e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1282 YLMEVTCSDNRRSLTKKSFEQFYRLHSQMQKQFSSLA--------LPEFPhwwhLPFTDSD-----HKRIRDLSHYVEQV 1348
Cdd:cd06890     17 YRVRATLSDGKTRYLCRYYQDFYKLHIALLDLFPAEAgrnsskriLPYLP----GPVTDVVndsisLKRLNDLNEYLNEL 92
                           90
                   ....*....|....*..
gi 1340723175 1349 LRGSYEVANSDCVLSFF 1365
Cdd:cd06890     93 INLPAYIQTSEVVRDFF 109
C2A_Synaptotagmin-15-17 cd08390
C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...
1399-1498 9.01e-03

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. 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: 176036 [Multi-domain]  Cd Length: 123  Bit Score: 37.62  E-value: 9.01e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1340723175 1399 YEDSRLTILVKHLKNIHLPDGSVPSAH----VEIYLLPhpSEVRRKKTKCVPKCTDPTYNEIVVYD-EVLGLQGHVLMLI 1473
Cdd:cd08390      9 YDLEEEQLTVSLIKARNLPPRTKDVAHcdpfVKVCLLP--DERRSLQSKVKRKTQNPNFDETFVFQvSFKELQRRTLRLS 86
                           90       100       110
                   ....*....|....*....|....*....|
gi 1340723175 1474 V-----KSKTVFVGAVniqlcSVPLNEEKW 1498
Cdd:cd08390     87 VydvdrFSRHCIIGHV-----LFPLKDLDL 111
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.19
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
  • Marchler-Bauer A et al. (2015), "CDD: NCBI's conserved domain database.", Nucleic Acids Res.43(D)222-6.
  • Marchler-Bauer A et al. (2011), "CDD: a Conserved Domain Database for the functional annotation of proteins.", Nucleic Acids Res.39(D)225-9.
  • Marchler-Bauer A, Bryant SH (2004), "CD-Search: protein domain annotations on the fly.", Nucleic Acids Res.32(W)327-331.
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