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Conserved domains on  [gi|1044420535|ref|XP_017361782|]
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phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform [Cebus imitator]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 695-1064 0e+00

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


:

Pssm-ID: 270719 [Multi-domain]  Cd Length: 370  Bit Score: 769.22  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  695 CGMYLKHLNRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSS 774
Cdd:cd05175      1 CGMYLKHLSRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  775 AKRPLWLNWENPDIMSELLFQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNS 854
Cdd:cd05175     81 AKRPLWLNWENPDIMSELLFQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNS 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  855 HTIMQIQCKGGLKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDF 934
Cdd:cd05175    161 HTIMQIQCKGGLKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDF 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  935 GHFLDHKKKKFGYKRERVPFVLTQDFLIVISKGAQECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQ 1014
Cdd:cd05175    241 GHFLDHKKKKFGYKRERVPFVLTQDFLIVISKGAQECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQ 320

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|
gi 1044420535 1015 SFDDIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQ 1064
Cdd:cd05175    321 SFDDIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQ 370
C2_PI3K_class_I_alpha cd08398
C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 325-484 3.67e-108

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


:

Pssm-ID: 176043  Cd Length: 158  Bit Score: 333.30  E-value: 3.67e-108
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  325 KSLWVINSALRIKILCATYVNVNirDIDKIYVRTGIYHGGEPLCDNVNTQRVPCSNPRWSEWLNYDIYIPDLPRAARLCL 404
Cdd:cd08398      1 KSLWKINSNLRIKILCATYVNVN--DIDKIYVRTGIYHGGEPLCDNVNTQRVPCSNPRWNEWLDYDIYIPDLPRSARLCL 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  405 SICSVKGRKGAKEEHCPLAWGNINLFDYTDTLVSGKMALNLWPVPHGLEDLLNPIGVTGSNPNKETPCLELEFDWFSSVV 484
Cdd:cd08398     79 SICSVKGRKGAKEEHCPLAWGNINLFDYTDTLVSGKMALNLWPVPHGLEDLLNPIGVTGSNPNKDTPCLELEFDRFSCVV 158
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 525-696 5.06e-102

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: 317.72  E-value: 5.06e-102
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  525 ENDKEQLRAICTRDPLSEITEQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPPIKPEQAMELLDC 604
Cdd:cd00872      1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRKKPQALPKLLLSVKWNKRDDVAQMYQLLKRWPKLKPEQALELLDC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  605 NYPDPMVRGFAVRCLEKyLTDDKLSQYLIQLVQVLKYEQYLDNLLVRFLLKKALTNQRIGHFFFWHLKSEMHNKTVSQRF 684
Cdd:cd00872     81 NFPDEHVREFAVRCLEK-LSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVSQRF 159

                          170
                   ....*....|..
gi 1044420535  685 GLLLESYCRACG 696
Cdd:cd00872    160 GLLLEAYLRGCG 171
PI3K_p85B smart00143
PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.
 31-108 1.10e-34

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


:

Pssm-ID: 197539  Cd Length: 78  Bit Score: 126.83  E-value: 1.10e-34
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1044420535    31 IVTLECLREATLVTIKHELFKEARKYPLHQLLQDESSYIFVSVTQEAEREEFFDETRRLCDLRLFQPFLKVIEPVGNR 108
Cdd:smart00143    1 LVTLRVLREATLSTIKHELFKQARKMPLGQLLQDESSYIFVSVNQTAEIEEFFDETRRLSDLRLFFPFLKLIEPVGNR 78
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 173-292 1.14e-27

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


:

Pssm-ID: 197540  Cd Length: 108  Bit Score: 108.18  E-value: 1.14e-27
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535   173 SSPELPKHIYNKLDKGQIIVVIWVIvspnNDKQKYTLKINHDCVPEQVIAEAIRKKtRSMLLSSEQLKLcvleyqgKYIL 252
Cdd:smart00144    1 TSPSVPEPLPLKTIANKILIVVHLE----KDQQTKTLKVNPNCTPDSVLAQAFTKM-LSLHDQVDPTSE-------DYIL 68

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|
gi 1044420535   253 KVCGCDEYFLEKYPLSQYKYIRSCIMLGRMPNLMLMAKES 292
Cdd:smart00144   69 KVCGRDEYLLGDHPLGSFEYIRNCLKNGTEPHLVLMTLSA 108
 
Name Accession Description Interval E-value
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 695-1064 0e+00

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


Pssm-ID: 270719 [Multi-domain]  Cd Length: 370  Bit Score: 769.22  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  695 CGMYLKHLNRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSS 774
Cdd:cd05175      1 CGMYLKHLSRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  775 AKRPLWLNWENPDIMSELLFQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNS 854
Cdd:cd05175     81 AKRPLWLNWENPDIMSELLFQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNS 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  855 HTIMQIQCKGGLKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDF 934
Cdd:cd05175    161 HTIMQIQCKGGLKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDF 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  935 GHFLDHKKKKFGYKRERVPFVLTQDFLIVISKGAQECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQ 1014
Cdd:cd05175    241 GHFLDHKKKKFGYKRERVPFVLTQDFLIVISKGAQECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQ 320

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|
gi 1044420535 1015 SFDDIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQ 1064
Cdd:cd05175    321 SFDDIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQ 370
C2_PI3K_class_I_alpha cd08398
C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 325-484 3.67e-108

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


Pssm-ID: 176043  Cd Length: 158  Bit Score: 333.30  E-value: 3.67e-108
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  325 KSLWVINSALRIKILCATYVNVNirDIDKIYVRTGIYHGGEPLCDNVNTQRVPCSNPRWSEWLNYDIYIPDLPRAARLCL 404
Cdd:cd08398      1 KSLWKINSNLRIKILCATYVNVN--DIDKIYVRTGIYHGGEPLCDNVNTQRVPCSNPRWNEWLDYDIYIPDLPRSARLCL 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  405 SICSVKGRKGAKEEHCPLAWGNINLFDYTDTLVSGKMALNLWPVPHGLEDLLNPIGVTGSNPNKETPCLELEFDWFSSVV 484
Cdd:cd08398     79 SICSVKGRKGAKEEHCPLAWGNINLFDYTDTLVSGKMALNLWPVPHGLEDLLNPIGVTGSNPNKDTPCLELEFDRFSCVV 158
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 525-696 5.06e-102

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: 317.72  E-value: 5.06e-102
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  525 ENDKEQLRAICTRDPLSEITEQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPPIKPEQAMELLDC 604
Cdd:cd00872      1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRKKPQALPKLLLSVKWNKRDDVAQMYQLLKRWPKLKPEQALELLDC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  605 NYPDPMVRGFAVRCLEKyLTDDKLSQYLIQLVQVLKYEQYLDNLLVRFLLKKALTNQRIGHFFFWHLKSEMHNKTVSQRF 684
Cdd:cd00872     81 NFPDEHVREFAVRCLEK-LSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVSQRF 159

                          170
                   ....*....|..
gi 1044420535  685 GLLLESYCRACG 696
Cdd:cd00872    160 GLLLEAYLRGCG 171
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 519-704 3.75e-89

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: 283.84  E-value: 3.75e-89
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  519 RDNELRENDKEQLRAICTRDPLSEITEQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPPIKPEQA 598
Cdd:pfam00613    1 KDLKPNEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYLMLVPKALTKLLLSVKWSDLSEVAEALSLLLKWAPIDPVDA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  599 MELLDCNYPDPMVRGFAVRCLEKyLTDDKLSQYLIQLVQVLKYEQYLDNLLVRFLLKKALTNQRIGHFFFWHLKSEMHNK 678
Cdd:pfam00613   81 LELLDPKFPDPEVRQYAVKCLES-ASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEIHDE 159

                          170       180
                   ....*....|....*....|....*.
gi 1044420535  679 TVSQRFGLLLESYCRACGMYLKHLNR 704
Cdd:pfam00613  160 EVSPRFGSLLELYLRSCGTSLLGLNK 185
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 521-704 1.51e-84

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: 271.05  E-value: 1.51e-84
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535   521 NELRENDKEQLRAICTRDPLSEITEQEKDFLWSHRHYCVT-IPEILPKLLLSVKWNSRDEVAQMYCLVKDWPPIKPEQAM 599
Cdd:smart00145    1 KPLDIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTnNPKALPKFLLSVKWSDADEVAQALSLLLSWAPLDPEDAL 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535   600 ELLDCNYPDPMVRGFAVRCLEKyLTDDKLSQYLIQLVQVLKYEQYLDNLLVRFLLKKALTNQRIGHFFFWHLKSEMHNKT 679
Cdd:smart00145   81 ELLDPKFPDPFVRAYAVKRLES-ASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPH 159

                           170       180
                    ....*....|....*....|....*
gi 1044420535   680 VSQRFGLLLESYCRACGMYLKHLNR 704
Cdd:smart00145  160 VSIRFGLLLEAYLRGCGTHLKELLK 184
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 799-1017 7.08e-78

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: 255.30  E-value: 7.08e-78
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535   799 IIFKNGDDLRQDMLTLQIIRIMENIWQN----QGLDLRMLPYGCLSIGDCVGLIEVVRNSHTIMQIQC------------ 862
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKdketRRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKeyrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535   863 -----------KGGLKGALQFNSHTLHQWLKDKNK--GEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQL 929
Cdd:smart00146   81 rsqtatrlkklELFLEATGKFPDPVLYDWFTKKFPdpSEDYFEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535   930 FHIDFGHFLDHKKKKFGYKrERVPFVLTQDFLIVISkgaqectKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSG 1009
Cdd:smart00146  161 FHIDFGFILGNGPKLFGFP-ERVPFRLTPEMVDVMG-------DSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDG 232


                    ....*...
gi 1044420535  1010 MPELQSFD 1017
Cdd:smart00146  233 LPDWRSGK 240
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 799-1015 5.25e-68

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: 227.98  E-value: 5.25e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  799 IIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDL-RMLPYGCLSIGDCVGLIEVVRNSHTIMQIQCKGGLKG--------A 869
Cdd:pfam00454    4 GIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEYGENGvpptamvkI 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  870 LQFNSHT------------------LHQWLKDKNKGEI-YDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMV-KDDGQL 929
Cdd:pfam00454   84 LHSALNYpklklefesrislppkvgLLQWFVKKSPDAEeWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTTGKL 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  930 FHIDFGHFLDHKKKKFGYKrERVPFVLTQDFLIVISkgaqectKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSG 1009
Cdd:pfam00454  164 FHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAMG-------PSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVADG 235


                   ....*.
gi 1044420535 1010 MPELQS 1015
Cdd:pfam00454  236 LPDWSI 241
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 350-482 1.67e-40

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: 145.97  E-value: 1.67e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  350 DIDKIYVRTGIYHGGEPLCDNVNTQRVPCSN--PRWSEWLNYDIYIPDLPRAARLCLSICSVKGRKGAkeeHCPLAWGNI 427
Cdd:pfam00792    1 RQEDLYVECQLYHGGKPLCLPVSTRYVPFSNssIKWNEWITFPIQISDLPRSARLCITIWDVSGPEKS---FVPIGWVNT 77

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1044420535  428 NLFDYTDTLVSGKMALNLWPVPHG----LEDLLNPIGVTGSNPNKETPCLELEFDWFSS 482
Cdd:pfam00792   78 SLFDKKGILRQGKQKLRLWPSKSTpgrsNVDEMNRLEKLLKKYERGQVSSVDWLDFLTF 136
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
799-1039 3.02e-35

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 146.47  E-value: 3.02e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  799 IIFKNGDDLRQDMLTLQIIRIMENIWQNQGL----DLRMLPYGCLSIGDCVGLIEVVRNSHTIMQI-------------- 860
Cdd:COG5032   1799 FIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGIIEWVPNSDTLHSIlreyhkrknisidq 1878

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  861 --------QCKGGLKG------ALQFNSHTLHQWLKDKNKGEI-YDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMV-K 924
Cdd:COG5032   1879 ekklaarlDNLKLLLKdefftkATLKSPPVLYDWFSESFPNPEdWLTARTNFARSLAVYSVIGYILGLGDRHPGNILIdR 1958

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  925 DDGQLFHIDFGHFLDHKKKKFGYKrERVPFVLTQDFLIVISKGAQECTktreferFQEMCYKAYLAIRQHANLFINLFSM 1004
Cdd:COG5032   1959 SSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAMGVSGVEGS-------FRELCETAFRALRKNADSLMNVLEL 2030

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|...
gi 1044420535 1005 MLGS------GMPELQ--SFDDIAYIRKTLALDKTEQEALEYF 1039
Cdd:COG5032   2031 FVRDpliewrRLPCFReiQNNEIVNVLERFRLKLSEKDAEKFV 2073
PI3K_p85B smart00143
PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.
 31-108 1.10e-34

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


Pssm-ID: 197539  Cd Length: 78  Bit Score: 126.83  E-value: 1.10e-34
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1044420535    31 IVTLECLREATLVTIKHELFKEARKYPLHQLLQDESSYIFVSVTQEAEREEFFDETRRLCDLRLFQPFLKVIEPVGNR 108
Cdd:smart00143    1 LVTLRVLREATLSTIKHELFKQARKMPLGQLLQDESSYIFVSVNQTAEIEEFFDETRRLSDLRLFFPFLKLIEPVGNR 78
PI3K_p85B pfam02192
PI3-kinase family, p85-binding domain;
34-107 1.11e-33

PI3-kinase family, p85-binding domain;


Pssm-ID: 460483  Cd Length: 74  Bit Score: 123.78  E-value: 1.11e-33
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1044420535   34 LECLREATLVTIKHELFKEARKYPLHQLLQDESSYIFVSVTQEAEREEFFDETRRLCDLRLFQPFLKVIEPVGN 107
Cdd:pfam02192    1 LRVSRNATLSEIKEELWEEAKKYPLYYLLKDPQSYVFTCINQTAEIEELYDETRRLCDVRPFFPILKLVEREGD 74
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 322-418 4.29e-29

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 111.67  E-value: 4.29e-29
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535   322 TSTKSLWVINSALRIKILCATYVNVN-IRDIDKIYVRTGIYHGGEPLCDNVNTQRVPCSNPR-WSEWLNYDIYIPDLPRA 399
Cdd:smart00142    1 VKIESLWDCDRNLVITIALIHGIPLNwSRDYSDLYVEIQLYHGGKLLCLPVSTSYKPFFPSVkWNEWLTFPIQISDLPRE 80

                            90       100
                    ....*....|....*....|
gi 1044420535   400 ARLCLSICSVKGR-KGAKEE 418
Cdd:smart00142   81 ARLCITIYAVKNPsKGSEFG 100
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 173-292 1.14e-27

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


Pssm-ID: 197540  Cd Length: 108  Bit Score: 108.18  E-value: 1.14e-27
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535   173 SSPELPKHIYNKLDKGQIIVVIWVIvspnNDKQKYTLKINHDCVPEQVIAEAIRKKtRSMLLSSEQLKLcvleyqgKYIL 252
Cdd:smart00144    1 TSPSVPEPLPLKTIANKILIVVHLE----KDQQTKTLKVNPNCTPDSVLAQAFTKM-LSLHDQVDPTSE-------DYIL 68

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|
gi 1044420535   253 KVCGCDEYFLEKYPLSQYKYIRSCIMLGRMPNLMLMAKES 292
Cdd:smart00144   69 KVCGRDEYLLGDHPLGSFEYIRNCLKNGTEPHLVLMTLSA 108
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 173-292 1.94e-25

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


Pssm-ID: 395642  Cd Length: 106  Bit Score: 101.60  E-value: 1.94e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  173 SSPELPKHIYnKLDKGQIIVVIWVIvspnNDKQKYTLKINHDCVPEQVIAEAIRKKtRSMLLSSEQlklcvleyQGKYIL 252
Cdd:pfam00794    1 ASTVSPEPLP-KLINNKLLISVHLE----GDQMTKTFTCNPNSTPGSLIAQALTKK-LSVHTQGDV--------TDDYVL 66

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1044420535  253 KVCGCDEYFLEKYPLSQYKYIRSCIMLGRMPNLMLMAKES 292
Cdd:pfam00794   67 KVCGRDEYLLGDHPLGQFEYIRNCLKSGREPHLTLVEQSS 106
 
Name Accession Description Interval E-value
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 695-1064 0e+00

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


Pssm-ID: 270719 [Multi-domain]  Cd Length: 370  Bit Score: 769.22  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  695 CGMYLKHLNRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSS 774
Cdd:cd05175      1 CGMYLKHLSRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  775 AKRPLWLNWENPDIMSELLFQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNS 854
Cdd:cd05175     81 AKRPLWLNWENPDIMSELLFQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNS 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  855 HTIMQIQCKGGLKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDF 934
Cdd:cd05175    161 HTIMQIQCKGGLKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDF 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  935 GHFLDHKKKKFGYKRERVPFVLTQDFLIVISKGAQECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQ 1014
Cdd:cd05175    241 GHFLDHKKKKFGYKRERVPFVLTQDFLIVISKGAQECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQ 320

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|
gi 1044420535 1015 SFDDIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQ 1064
Cdd:cd05175    321 SFDDIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQ 370
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 699-1064 0e+00

Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. In vitro, they can also phosphorylate the substrates PtdIns and PtdIns(4)P. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270709 [Multi-domain]  Cd Length: 363  Bit Score: 660.10  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  699 LKHLNRQVEAMEKLINLTDILKQEKKDetqKVQMKFLVEQMRRPDF-MDALQGFLSPLNPAHQLGNLRLEECRIMSSAKR 777
Cdd:cd05165      1 LKSLSRQVEALNKLKKLSDILKEKKKS---KEKVKKLLKECLKQKFyDEALQNFQSPLNPSHKLGELIIEKCKVMDSKKR 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  778 PLWLNWENPDIMSeLLFQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHTI 857
Cdd:cd05165     78 PLWLVFENADPLA-LSGEDIKIIFKNGDDLRQDMLTLQIIRIMDNIWKEEGLDLRMLPYGCLSTGDNVGLIEVVRNAKTI 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  858 MQIQCKGGLKGALQFNSHTLHQWLKDKNK-GEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGH 936
Cdd:cd05165    157 ANIQKKKGKVATLAFNKDSLHKWLKEKNKtGEKYDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVKENGQLFHIDFGH 236

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  937 FLDHKKKKFGYKRERVPFVLTQDFLIVISKGAQEcTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSF 1016
Cdd:cd05165    237 FLGNFKKKFGIKRERVPFVLTHDFVYVIARGQDN-TKSEEFQEFQELCEKAYLILRRHGNLFISLFSMMLSTGIPELTSV 315

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*...
gi 1044420535 1017 DDIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQ 1064
Cdd:cd05165    316 KDIEYLRKTLALDKTEEEALKYFRKKFNEALKGSWTTKVNWFFHNVKH 363
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 702-1046 2.35e-148

Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. Class II PI3Ks comprise three catalytic isoforms that do not associate with any regulatory subunits. They selectively use PtdIns as a susbtrate to produce PtsIns(3)P. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270624 [Multi-domain]  Cd Length: 334  Bit Score: 445.86  E-value: 2.35e-148
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  702 LNRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEqmrrpdfMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKRPLWL 781
Cdd:cd00891      4 LLKQVKVLDELKEIAKKIKEEPSEERKEVLEKLLQK-------LELPKKFTLPLDPRMEVKGLIVEKCKVMDSKKLPLWL 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  782 NWENPDIMSELLFqnneIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHTIMQIQ 861
Cdd:cd00891     77 VFKNADPGGDPIK----VIFKAGDDLRQDQLTLQLLRIMDKLWKKEGLDLRMTPYKCIATGDEVGMIEVVPNSETTAAIQ 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  862 CKGGLKGALqFNSHTLHQWLKDKNKGE-IYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGHFLDH 940
Cdd:cd00891    153 KKYGGFGAA-FKDTPISNWLKKHNPTEeEYEEAVENFIRSCAGYCVATYVLGIGDRHNDNIMVTKSGHLFHIDFGHFLGN 231

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  941 KKKKFGYKRERVPFVLTQDFLIVIskGAQECTKtreFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSFDDIA 1020
Cdd:cd00891    232 FKKKFGIKRERAPFVFTPEMAYVM--GGEDSEN---FQKFEDLCCKAYNILRKHGNLLINLFSLMLSAGIPELQSIEDIE 306

                          330       340
                   ....*....|....*....|....*.
gi 1044420535 1021 YIRKTLALDKTEQEALEYFMKQMNDA 1046
Cdd:cd00891    307 YLRDALQLDLSDEEAAEHFRKLIHES 332
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 698-1064 1.34e-127

Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kdelta is mainly expressed in immune cells and plays an important role in cellular and humoral immunity. It plays a major role in antigen receptor signaling in B-cells, T-cells, and mast cells. It regulates the differentiation of peripheral helper T-cells and controls the development and function of regulatory T-cells. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). Class IA enzymes contain an N-terminal p85 binding domain, a Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. They associate with a regulatory subunit of the p85 family and are activated by tyrosine kinase receptors. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270718 [Multi-domain]  Cd Length: 366  Bit Score: 392.88  E-value: 1.34e-127
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  698 YLKHLNRQVEAMEKLINLTDILKQEKKDETqKVQMKFLVEQ-MRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAK 776
Cdd:cd05174      3 HMKVLMKQGEALSKMKALNDFVKVSSQKAT-KPQTKEMMHVcMKQETYMEALSHLQSPLDPSIILEEVCVDQCTFMDSKM 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  777 RPLWLNWENpdimSELLFQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHT 856
Cdd:cd05174     82 KPLWIMYSS----EEAGAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDT 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  857 IMQIQC-KGGLKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFG 935
Cdd:cd05174    158 IANIQLnKSNMAATAAFNKDALLNWLKSKNPGDALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDFG 237

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  936 HFLDHKKKKFGYKRERVPFVLTQDFLIVISKGaqECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQS 1015
Cdd:cd05174    238 HFLGNFKTKFGINRERVPFILTYDFVHVIQQG--KTNNSEKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSC 315

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*....
gi 1044420535 1016 FDDIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQ 1064
Cdd:cd05174    316 SKDIQYLKDSLALGKTEEEALKHFRVKFNEALRESWKTKVNWLAHNVSK 364
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 699-1064 6.08e-127

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: 391.25  E-value: 6.08e-127
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  699 LKHLNRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKRP 778
Cdd:cd05173      1 MKVLSKQVEALNKLKTLNSLIKLNAVKLSKAKGKEAMHTCLRQSAYREALSDLQSPLNPSIILSELNVEKCKYMDSKMKP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  779 LWLNWENPDIMSELLfqnnEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHTIM 858
Cdd:cd05173     81 LWIVYNNKLFGGDSL----GIIFKNGDDLRQDMLTLQILRLMDTLWKEAGLDLRIVPYGCLATGDRSGLIEVVSSAETIA 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  859 QIQC-KGGLKGALQFNSHTLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGHF 937
Cdd:cd05173    157 DIQLnSSNVAAAAAFNKDALLNWLKEYNSGDDLERAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHI 236

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  938 LDHKKKKFGYKRERVPFVLTQDFLIVISKGaqECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSFD 1017
Cdd:cd05173    237 LGNFKSKFGIKRERVPFILTYDFIHVIQQG--KTGNTEKFGRFRQYCEDAYLILRKNGNLFITLFALMLTAGLPELTSVK 314

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*..
gi 1044420535 1018 DIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTIKQ 1064
Cdd:cd05173    315 DIQYLKDSLALGKSEEEALKQFRQKFDEALRESWTTKVNWMAHTVRK 361
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 702-1064 1.81e-112

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


Pssm-ID: 270710 [Multi-domain]  Cd Length: 352  Bit Score: 352.36  E-value: 1.81e-112
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  702 LNRQVEAMEKLINLTDILKQEKKDETQKVqmkflveqMRRPdfMDALQGFLS------PLNPAHQLGNLRLEECRIMSSA 775
Cdd:cd05166      4 FLKQHVLVQALTSIAEKVKSAKDSARENA--------LRRE--LEQLASFLLensfrlPLDPALEVTGVDVRSCSYFNSN 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  776 KRPLWLNWENPDIMSELLfqnnEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSH 855
Cdd:cd05166     74 ALPLKLVFRNADPRAEPI----SVIFKVGDDLRQDMLTLQLIRIMDKIWLQEGLDLKMITFRCVPTGNKRGMVELVPEAE 149

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  856 TIMQIQCKGGLKGAlqFNSHTLHQWLKDKNKGEI-YDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDF 934
Cdd:cd05166    150 TLREIQTEHGLTGS--FKDRPLADWLQKHNPSELeYEKAVENFIRSCAGYCVATYVLGICDRHNDNIMLKTSGHLFHIDF 227

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  935 GHFLDHKKKKFGYKRERVPFVLTQDFLIVISKGAQectKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQ 1014
Cdd:cd05166    228 GKFLGDAQMFGNFKRDRVPFVLTSDMAYVINGGDK---PSSRFQLFVDLCCQAFNIIRKNSNLLLNLLSLMLSSGIPGVT 304

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|
gi 1044420535 1015 SfDDIAYIRKTLALDKTEQEALEYFMKQMNDAhHGGWTTKMDWIFHTIKQ 1064
Cdd:cd05166    305 Q-DDLRYVQDALLPELTDAEATAHFTRMIEES-LSSKFTQLNFFIHNLAQ 352
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 699-1062 1.41e-111

Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. PI3Kgamma signaling controls diverse immune and vascular functions including cell recruitment, mast cell activation, platelet aggregation, and smooth muscle contractility. It associates with one of two regulatory subunits, p101 and p84, and is activated by G-protein-coupled receptors (GPCRs) by direct binding to their betagamma subunits. It contains an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, and a C-terminal ATP-binding cataytic domain. PI3Ks can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class I PI3Ks are the only enzymes capable of converting PtdIns(4,5)P2 to the critical second messenger PtdIns(3,4,5)P3. Class I enzymes are heterodimers and exist in multiple isoforms consisting of one catalytic subunit (out of four isoforms) and one of several regulatory subunits. They are further classified into class IA (alpha, beta and delta) and IB (gamma). The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270627 [Multi-domain]  Cd Length: 367  Bit Score: 350.70  E-value: 1.41e-111
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  699 LKHLNRQVEAMEKLINLTDILKQ---EKKDETQKV--QMKFLVEQMRRPDFMDAlqgFLSPLNPAHQLGNLRLEECRIMS 773
Cdd:cd00894      1 LHDFTQQVQVIEMLQKVTLDIKSlsaEKYDVSSQVisQLKQKLENLQNSQLPES---FRVPYDPGLRAGALVIEKCKVMA 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  774 SAKRPLWLNWENPDiMSELLFQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRN 853
Cdd:cd00894     78 SKKKPLWLEFKCAD-PTALSNETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKD 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  854 SHTIMQIQ-CKGGLKGAlqFNSHTLHQWLKDKNK-GEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFH 931
Cdd:cd00894    157 ATTIAKIQqSTVGNTGA--FKDEVLNHWLKEKCPiEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFH 234

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  932 IDFGHFLDHKKKKFGYKRERVPFVLTQDFLIVIskGAQECTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMP 1011
Cdd:cd00894    235 IDFGHILGNYKSFLGINKERVPFVLTPDFLFVM--GTSGKKTSLHFQKFQDVCVKAYLALRHHTNLLIILFSMMLMTGMP 312

                          330       340       350       360       370
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1044420535 1012 ELQSFDDIAYIRKTLALDKTEQEALEYFMKQMNDAHHGGWTTKMDWIFHTI 1062
Cdd:cd00894    313 QLTSKEDIEYIRDALTVGKSEEDAKKHFLDQIEVCRDKGWTVQFNWFLHLV 363
C2_PI3K_class_I_alpha cd08398
C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 325-484 3.67e-108

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


Pssm-ID: 176043  Cd Length: 158  Bit Score: 333.30  E-value: 3.67e-108
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  325 KSLWVINSALRIKILCATYVNVNirDIDKIYVRTGIYHGGEPLCDNVNTQRVPCSNPRWSEWLNYDIYIPDLPRAARLCL 404
Cdd:cd08398      1 KSLWKINSNLRIKILCATYVNVN--DIDKIYVRTGIYHGGEPLCDNVNTQRVPCSNPRWNEWLDYDIYIPDLPRSARLCL 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  405 SICSVKGRKGAKEEHCPLAWGNINLFDYTDTLVSGKMALNLWPVPHGLEDLLNPIGVTGSNPNKETPCLELEFDWFSSVV 484
Cdd:cd08398     79 SICSVKGRKGAKEEHCPLAWGNINLFDYTDTLVSGKMALNLWPVPHGLEDLLNPIGVTGSNPNKDTPCLELEFDRFSCVV 158
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 525-696 5.06e-102

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: 317.72  E-value: 5.06e-102
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  525 ENDKEQLRAICTRDPLSEITEQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPPIKPEQAMELLDC 604
Cdd:cd00872      1 NEEREQLEAIIARDPLSELTEEDKELLWKLRHECRKKPQALPKLLLSVKWNKRDDVAQMYQLLKRWPKLKPEQALELLDC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  605 NYPDPMVRGFAVRCLEKyLTDDKLSQYLIQLVQVLKYEQYLDNLLVRFLLKKALTNQRIGHFFFWHLKSEMHNKTVSQRF 684
Cdd:cd00872     81 NFPDEHVREFAVRCLEK-LSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVSQRF 159

                          170
                   ....*....|..
gi 1044420535  685 GLLLESYCRACG 696
Cdd:cd00872    160 GLLLEAYLRGCG 171
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 519-704 3.75e-89

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: 283.84  E-value: 3.75e-89
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  519 RDNELRENDKEQLRAICTRDPLSEITEQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPPIKPEQA 598
Cdd:pfam00613    1 KDLKPNEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYLMLVPKALTKLLLSVKWSDLSEVAEALSLLLKWAPIDPVDA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  599 MELLDCNYPDPMVRGFAVRCLEKyLTDDKLSQYLIQLVQVLKYEQYLDNLLVRFLLKKALTNQRIGHFFFWHLKSEMHNK 678
Cdd:pfam00613   81 LELLDPKFPDPEVRQYAVKCLES-ASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEIHDE 159

                          170       180
                   ....*....|....*....|....*.
gi 1044420535  679 TVSQRFGLLLESYCRACGMYLKHLNR 704
Cdd:pfam00613  160 EVSPRFGSLLELYLRSCGTSLLGLNK 185
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 521-704 1.51e-84

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: 271.05  E-value: 1.51e-84
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535   521 NELRENDKEQLRAICTRDPLSEITEQEKDFLWSHRHYCVT-IPEILPKLLLSVKWNSRDEVAQMYCLVKDWPPIKPEQAM 599
Cdd:smart00145    1 KPLDIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYLTnNPKALPKFLLSVKWSDADEVAQALSLLLSWAPLDPEDAL 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535   600 ELLDCNYPDPMVRGFAVRCLEKyLTDDKLSQYLIQLVQVLKYEQYLDNLLVRFLLKKALTNQRIGHFFFWHLKSEMHNKT 679
Cdd:smart00145   81 ELLDPKFPDPFVRAYAVKRLES-ASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPH 159

                           170       180
                    ....*....|....*....|....*
gi 1044420535   680 VSQRFGLLLESYCRACGMYLKHLNR 704
Cdd:smart00145  160 VSIRFGLLLEAYLRGCGTHLKELLK 184
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 703-1064 1.35e-82

Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II gamma isoform, PI3K-C2gamma, is expressed in the liver, breast, and prostate. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. It's biological function remains unknown. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270721 [Multi-domain]  Cd Length: 354  Bit Score: 272.54  E-value: 1.35e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  703 NRQVEAMEKLIN-LTDILKQEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKRPLWL 781
Cdd:cd05177      1 NKEFSKETKLISiLIDAAEKVKTASDTRRKEVLKREASRLEDFFQDVVSCCLPLNPALRVKGIDADACSYFTSNAAPLKI 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  782 NWENPDIMSellfQNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHTIMQIQ 861
Cdd:cd05177     81 SFINANPLA----KNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYRCLSTGKTQGLVQMVPDAVTLAKIH 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  862 CKGGLKGALQFNshTLHQWLKDKNK-GEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGHFLDH 940
Cdd:cd05177    157 RESGLIGPLKEN--TIEKWFHMHNKlKEDYDKAVRNFFHSCAGWCVVTFILGVCDRHNDNIMLTHSGHMFHIDFGKFLGH 234

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  941 KKKKFGYKRERVPFVLTQDFLIVISKGAQectKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSFDDIA 1020
Cdd:cd05177    235 AQTFGSIKRDRAPFIFTSEMEYFITEGGK---KPQRFQRFVELCCRAYNIVRKHSQLLLNLLEMMLHAGLPELKDIQDLK 311

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....
gi 1044420535 1021 YIRKTLALDKTEQEALEYFMKQMNDAHHgGWTTKMDWIFHTIKQ 1064
Cdd:cd05177    312 YVYNNLRPQDTDLEATSYFTKKIKESLE-CFPVKLNNLIHTLAQ 354
PI3Kc_C2_alpha cd05176
Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 705-1064 3.72e-81

Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives. The class II alpha isoform, PI3K-C2alpha, plays key roles in clathrin assembly and clathrin-mediated membrane trafficking, insulin signaling, vascular smooth muscle contraction, and the priming of neurosecretory granule exocytosis. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They can be divided into three main classes (I, II, and III), defined by their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PtdIns as a substrate to produce PtdIns(3)P, but can also phosphorylate PtdIns(4)P. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a Phox homology (PX) domain, and a second C2 domain at the C-terminus. The PI3K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270720 [Multi-domain]  Cd Length: 353  Bit Score: 268.77  E-value: 3.72e-81
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  705 QVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRRpdfmdaLQGFLS------PLNPAHQLGNLRLEECRIMSSAKRP 778
Cdd:cd05176      3 ELEKQTRLVQLLGRVAEKVRQASGSARQVALQDGMER------VQSFFQknkcrlPLSPSLVAKELNIKACSFFSSNAVP 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  779 LWLNWENPDIMSELLfqnnEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHTIM 858
Cdd:cd05176     77 LKVALVNADPLGEEI----NVMFKVGEDLRQDMLALQMIKIMDKIWLQEGLDLRMVIFKCLSTGKDRGMVELVPSSDTLR 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  859 QIQCKGGLKGAlqFNSHTLHQWLKDKNKGEI-YDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGHF 937
Cdd:cd05176    153 KIQVEYGVTGS--FKDKPLAEWLRKYNPSEEeYEKASENFIYSCAGCCVATYVLGICDRHNDNIMLRSTGHMFHIDFGKF 230

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  938 LDHKKKKFGYKRERVPFVLTQDFLIVISKGAQectKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSFD 1017
Cdd:cd05176    231 LGHAQMFGSFKRDRAPFVLTSDMAYVINGGEK---PTIRFQLFVDLCCQAYNLIRKHTNLFLNLLSLMLSSGLPELTGIQ 307

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*..
gi 1044420535 1018 DIAYIRKTLALDKTEQEALEYFMKQMnDAHHGGWTTKMDWIFHTIKQ 1064
Cdd:cd05176    308 DLKYVFDALQPQTTDAEATIFFTRLI-ESSLGSVATKFNFFIHNLAQ 353
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 799-1017 7.08e-78

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: 255.30  E-value: 7.08e-78
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535   799 IIFKNGDDLRQDMLTLQIIRIMENIWQN----QGLDLRMLPYGCLSIGDCVGLIEVVRNSHTIMQIQC------------ 862
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKdketRRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKeyrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535   863 -----------KGGLKGALQFNSHTLHQWLKDKNK--GEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQL 929
Cdd:smart00146   81 rsqtatrlkklELFLEATGKFPDPVLYDWFTKKFPdpSEDYFEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535   930 FHIDFGHFLDHKKKKFGYKrERVPFVLTQDFLIVISkgaqectKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSG 1009
Cdd:smart00146  161 FHIDFGFILGNGPKLFGFP-ERVPFRLTPEMVDVMG-------DSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDG 232


                    ....*...
gi 1044420535  1010 MPELQSFD 1017
Cdd:smart00146  233 LPDWRSGK 240
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 754-1064 6.77e-75

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


Pssm-ID: 119421 [Multi-domain]  Cd Length: 354  Bit Score: 251.46  E-value: 6.77e-75
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  754 PLNPAHQLGNLRLEECRIMSSAKRPLWLNWENPDIMSEllfqNNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRM 833
Cdd:cd00895     53 PLSPSLLVKGIVPRDCSYFNSNAVPLKLSFQNVDPLGE----NIRVIFKCGDDLRQDMLTLQMIRIMNKIWVQEGLDMRM 128

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  834 LPYGCLSIGDCVGLIEVVRNSHTIMQIQCKGGLKGAlqFNSHTLHQWLKDKNKGEI-YDAAIDLFTRSCAGYCVATFILG 912
Cdd:cd00895    129 VIFRCFSTGRGRGMVEMIPNAETLRKIQVEHGVTGS--FKDRPLADWLQKHNPTEDeYEKAVENFIYSCAGCCVATYVLG 206

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  913 IGDRHNSNIMVKDDGQLFHIDFGHFLDHKKKKFGYKRERVPFVLTQDFLIVISKGAQECTKtreFERFQEMCYKAYLAIR 992
Cdd:cd00895    207 ICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGNIKRDRAPFVFTSDMAYVINGGDKPSSR---FHDFVDLCCQAYNLIR 283

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1044420535  993 QHANLFINLFSMMLGSGMPELQSFDDIAYIRKTLALDKTEQEALEYFMKQMnDAHHGGWTTKMDWIFHTIKQ 1064
Cdd:cd00895    284 KHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQDTEADATTYFTRLI-ESSLGSVATKLNFFIHNLAQ 354
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 700-1046 1.02e-71

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: 242.05  E-value: 1.02e-71
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  700 KHLNRQVEAMEKLINLTDILKQEKKDETQKvqMKFLVEQMRRPDFMDALQ--GFLSPLNPAHQLGNLRLEECRIMSSAKR 777
Cdd:cd00896      2 EALKRQQEFVDRLRSLMKEVKNEKGSRDKK--IERLRELLSDSELGLLLFfePLPLPLDPSVKVTGIIPEKSTVFKSALM 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  778 PLWLNWENPDIMSELlfqnneIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHTI 857
Cdd:cd00896     80 PLKLTFKTLDGGEYK------VIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVPNSKAL 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  858 MQIQCKGGlkgalqfnshTLHQWLKDKNKGE-----IYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHI 932
Cdd:cd00896    154 ADILKKYG----------SILNFLRKHNPDEsgpygIKPEVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHI 223

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  933 DFGHFLDHKKKKFgykreRVPFVLTQDFLiviskgaqEC---TKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSG 1009
Cdd:cd00896    224 DFGYILGRDPKPF-----PPPMKLCKEMV--------EAmggANSEGYKEFKKYCCTAYNILRKHANLILNLFSLMVDAN 290

                          330       340       350
                   ....*....|....*....|....*....|....*....
gi 1044420535 1010 MPELQSFDD--IAYIRKTLALDKTEQEALEYFMKQMNDA 1046
Cdd:cd00896    291 IPDIALEPDkaVLKVQEKFRLDLSDEEAEQYFQNLIDES 329
PI3Ka cd00864
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 527-677 4.11e-68

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: 224.79  E-value: 4.11e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  527 DKEQLRAICTRDPLSEITEQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPPIKPEQAMELLDCNY 606
Cdd:cd00864      3 ERKPLLAILLYPPFSTLTEEEKELLWKFRYYLLNVPKALPKLLKSVNWNDDEEVSELYQLLKWWAPLSPEDALELLSPKY 82

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1044420535  607 PDPMVRGFAVRCLEKYlTDDKLSQYLIQLVQVLKYEQYLDNLLVRFLLKKALTNQRIGHFFFWHLKSEMHN 677
Cdd:cd00864     83 PDPVVRQYAVRVLESA-SDDELLLYLPQLVQALKYEPYLDSYLARFLLERALKSQRLGHQLYWNLKSEIHD 152
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 799-1015 5.25e-68

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: 227.98  E-value: 5.25e-68
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  799 IIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDL-RMLPYGCLSIGDCVGLIEVVRNSHTIMQIQCKGGLKG--------A 869
Cdd:pfam00454    4 GIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEYGENGvpptamvkI 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  870 LQFNSHT------------------LHQWLKDKNKGEI-YDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMV-KDDGQL 929
Cdd:pfam00454   84 LHSALNYpklklefesrislppkvgLLQWFVKKSPDAEeWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTTGKL 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  930 FHIDFGHFLDHKKKKFGYKrERVPFVLTQDFLIVISkgaqectKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSG 1009
Cdd:pfam00454  164 FHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAMG-------PSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVADG 235


                   ....*.
gi 1044420535 1010 MPELQS 1015
Cdd:pfam00454  236 LPDWSI 241
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
 800-1058 7.39e-59

Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 4-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) to generate PtdIns(4)P, the major precursor in the synthesis of other phosphoinositides including PtdIns(4,5)P2, PtdIns(3,4)P2, and PtdIns(3,4,5)P3. Two isoforms of type III PI4K, alpha and beta, exist in most eukaryotes. PI4KIIIalpha is a 220 kDa protein found in the plasma membrane and the endoplasmic reticulum (ER). The role of PI4KIIIalpha in the ER remains unclear. In the plasma membrane, it provides PtdIns(4)P, which is then converted by PI5Ks to PtdIns(4,5)P2, an important signaling molecule. Vertebrate PI4KIIIalpha is also part of a signaling complex associated with P2X7 ion channels. The yeast homolog, Stt4p, is also important in regulating the conversion of phosphatidylserine to phosphatidylethanolamine at the ER and Golgi interface. Mammalian PI4KIIIalpha is highly expressed in the nervous system. The PI4K catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270711 [Multi-domain]  Cd Length: 307  Bit Score: 204.75  E-value: 7.39e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  800 IFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIG-DCvGLIEVVRNSHTIMQIqckgglkGALQFNShtLH 878
Cdd:cd05167     53 IFKVGDDCRQDMLALQLISLFKNIFEEVGLDLYLFPYRVVATGpGC-GVIEVIPNSKSRDQI-------GRETDNG--LY 122

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  879 QWLKDK---NKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGHFLD---HKKKKFgykrERV 952
Cdd:cd05167    123 EYFLSKygdESTPAFQKARRNFIKSMAGYSLVSYLLQIKDRHNGNIMIDDDGHIIHIDFGFIFEispGGNLGF----ESA 198

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  953 PFVLTQDFlIVISKGAQEctkTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPelqSF--DDIAYIRKTLALDK 1030
Cdd:cd05167    199 PFKLTKEM-VDLMGGSME---SEPFKWFVELCVRGYLAVRPYAEAIVSLVELMLDSGLP---CFrgQTIKNLRERFALEM 271

                          250       260
                   ....*....|....*....|....*....
gi 1044420535 1031 TEQEALEYFMKQMNDAHHgGWTTKM-DWI 1058
Cdd:cd05167    272 SEREAANFMIKLIADSYL-KIRTKGyDMF 299
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
 796-1054 1.04e-51

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: 183.62  E-value: 1.04e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  796 NNEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHTIMQIQCKggLKGALQFnsH 875
Cdd:cd00893     27 LVSLIVKTGDDLKQEQLALQLISQFDQIFKEEGLPLWLRPYEILSLGPDSGIIEMIKNAVSIDSLKKK--LDSFNKF--V 102

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  876 TLHQWLKDKNKGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGHFL-DHKKKkfgYKRERVPF 954
Cdd:cd00893    103 SLSDFFDDNFGDEAIQKARDNFLQSLVAYSLVCYFLQIKDRHNGNILLDKEGHIIHIDFGFFLsSHPGF---YGFEGAPF 179

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  955 VLTQDFLIVISKgaqecTKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSFDDIAYIRKTLALDKTEQE 1034
Cdd:cd00893    180 KLSSEYIEVLGG-----VDSELFKEFRKLFLKGFMALRKHSDKILSLVEMMYSGHGITCFGKKTIQQLKQRFNPELTEGE 254

                          250       260
                   ....*....|....*....|
gi 1044420535 1035 ALEYFMKQMNDAhHGGWTTK 1054
Cdd:cd00893    255 LEVYVLSLINKS-LDNWRTR 273
C2_PI3K_like cd08380
C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes ...
 325-484 2.45e-51

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: 177.55  E-value: 2.45e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  325 KSLWVINSALRIKILCATYVNVNIRDIDKIYVRTGIYHGGEPLCDNVNTQRVPC-SNPRWSEWLNYDIYIPDLPRAARLC 403
Cdd:cd08380      1 KSLWDINFNLRIKIHGITNINLLDSEDLKLYVRVQLYHGGEPLCPPQSTKKVPFsTSVTWNEWLTFDILISDLPREARLC 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  404 LSICSVKGRKgaKEEHCPLAWGNINLFDYTDTLVSGKMALNLWPVPHGLEDLLNPIgvtGSNPNKETPCLELEFDWFSSV 483
Cdd:cd08380     81 LSIYAVSEPG--SKKEVPLGWVNVPLFDYKGKLRQGMITLNLWPGKKTDPRIACTP---CNNSNENSTRLLIELPEFSKP 155


                   .
gi 1044420535  484 V 484
Cdd:cd08380    156 V 156
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
 799-1055 6.54e-48

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: 172.67  E-value: 6.54e-48
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  799 IIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHTIMQIQCKGGLKGALQfnsHTLH 878
Cdd:cd05168     33 VIVKSGDDLRQELLAMQLIKQFQRIFEEAGLPLWLRPYEILVTSSDSGLIETIPDTVSIDSLKKRFPNFTSLL---DYFE 109

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  879 QWLKDKNkGEIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGHFLDHKKKKFGYkrERVPFVLTQ 958
Cdd:cd05168    110 RTFGDPN-SERFKEAQRNFVESLAAYSLVCYLLQIKDRHNGNILLDSEGHIIHIDFGFMLSNSPGGLGF--ETAPFKLTQ 186

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  959 DFLIVIskGAQECTKtreFERFQEMCYKAYLAIRQHANLFINLFSMML-GSGMPELQSFDD--IAYIRKTLALDKTEQEa 1035
Cdd:cd05168    187 EYVEVM--GGLESDM---FRYFKTLMIQGFLALRKHADRIVLLVEIMQqGSKLPCFFGGGEftIEQLRERFKLNLTEEE- 260

                          250       260
                   ....*....|....*....|
gi 1044420535 1036 LEYFMKQMNDAHHGGWTTKM 1055
Cdd:cd05168    261 CAQFVDSLIDKSLNNWRTRQ 280
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
 769-1007 1.92e-44

Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family include PI3K, phosphoinositide 4-kinase (PI4K), PI3K-related protein kinases (PIKKs), and TRansformation/tRanscription domain-Associated Protein (TRAPP). PI3Ks catalyze the transfer of the gamma-phosphoryl group from ATP to the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives, while PI4K catalyze the phosphorylation of the 4-hydroxyl of PtdIns. PIKKs are protein kinases that catalyze the phosphorylation of serine/threonine residues, especially those that are followed by a glutamine. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI4Ks produce PtdIns(4)P, the major precursor to important signaling phosphoinositides. PIKKs have diverse functions including cell-cycle checkpoints, genome surveillance, mRNA surveillance, and translation control. The PI3K-like catalytic domain family is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270621 [Multi-domain]  Cd Length: 216  Bit Score: 160.19  E-value: 1.92e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  769 CRIMSSAKRPLW--LNWENPDIMSellfqnneIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVG 846
Cdd:cd00142      8 LKVIHSKQRPKKitLIGADGKTYS--------FLLKRRDDLRKDERSFQFMRLIQSILEKESVNLVLPPYKVIPLSENSG 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  847 LIEVVRNSHTImqiqckgglkgalqfnsHTLHQWLKDKNKG-EIYDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKD 925
Cdd:cd00142     80 LIEIVKDAQTI-----------------EDLLKSLWRKSPSsQSWLNRRENFSCSLAGYSVLGYIFGIGDRHPSNIMIEP 142

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  926 DGQLFHIDFGHFLDHKKKKFGYkrERVPFVLTQDFLIVISKGAQectktreFERFQEMCYKAYLAIRQHANLFINLFSMM 1005
Cdd:cd00142    143 SGNIFHIDFGFIFSGRKLAEGV--ETVPFRLTPMLENAMGTAGV-------NGPFQISMVKIMEILREHADLIVPILEHS 213


                   ..
gi 1044420535 1006 LG 1007
Cdd:cd00142    214 LR 215
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 325-478 1.07e-40

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


Pssm-ID: 176075  Cd Length: 173  Bit Score: 147.84  E-value: 1.07e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  325 KSLWVINSALRIKILCATYVNVNIRDiDKIYVRTGIYHGGEPLCDNVNTQRVP-CSNPRWSEWLNYDIYIPDLPRAARLC 403
Cdd:cd08693      1 KSLWDIEEKFSITLHKISNLNAAERT-MKVGVQAGLFHGGESLCKTVKTSEVSgKNDPVWNETLEFDINVCDLPRMARLC 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  404 LSICSV----KGRKGAKEE--------HCPLAWGNINLFDYTDTLVSGKMALNLWPVPH-GLEDLLNPIGVTGSNPNKE- 469
Cdd:cd08693     80 FAIYEVskkaKGKRSRKNQtkkkkkkdDNPIAWVNTMVFDYKGQLKTGDHTLYMWTYAEdQSEDLLNPLGTVESNPNTEs 159


                   ....*....
gi 1044420535  470 TPCLELEFD 478
Cdd:cd08693    160 ATALHISFP 168
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 350-482 1.67e-40

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: 145.97  E-value: 1.67e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  350 DIDKIYVRTGIYHGGEPLCDNVNTQRVPCSN--PRWSEWLNYDIYIPDLPRAARLCLSICSVKGRKGAkeeHCPLAWGNI 427
Cdd:pfam00792    1 RQEDLYVECQLYHGGKPLCLPVSTRYVPFSNssIKWNEWITFPIQISDLPRSARLCITIWDVSGPEKS---FVPIGWVNT 77

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*....
gi 1044420535  428 NLFDYTDTLVSGKMALNLWPVPHG----LEDLLNPIGVTGSNPNKETPCLELEFDWFSS 482
Cdd:pfam00792   78 SLFDKKGILRQGKQKLRLWPSKSTpgrsNVDEMNRLEKLLKKYERGQVSSVDWLDFLTF 136
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
 525-688 4.49e-37

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: 137.20  E-value: 4.49e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  525 ENDKEQLRAICTRDPLSEITEQEKDFLWSHRHYCVTIPEILPKLLLSVK-WNSRDeVAQMYCLVKDWPPIKPEQAMELLD 603
Cdd:cd00869      1 IETQEKLLDLIQKQSTYTLSTEDKDLLWEKRLYCTNEPNALPLVLASAPsWDWAN-LMDVYQLLHQWAPLRPLIALELLL 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  604 CNYPDPMVRGFAVRCLEKyLTDDKLSQYLIQLVQVLKYEQYLDNLLVRFLLKKALTNQRIGHFFFWHLKSEMHNKTVSQR 683
Cdd:cd00869     80 PKFPDQEVRAHAVQWLAR-LSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALDDCYFSSA 158


                   ....*
gi 1044420535  684 FGLLL 688
Cdd:cd00869    159 YQDLG 163
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
799-1039 3.02e-35

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 146.47  E-value: 3.02e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  799 IIFKNGDDLRQDMLTLQIIRIMENIWQNQGL----DLRMLPYGCLSIGDCVGLIEVVRNSHTIMQI-------------- 860
Cdd:COG5032   1799 FIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGIIEWVPNSDTLHSIlreyhkrknisidq 1878

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  861 --------QCKGGLKG------ALQFNSHTLHQWLKDKNKGEI-YDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMV-K 924
Cdd:COG5032   1879 ekklaarlDNLKLLLKdefftkATLKSPPVLYDWFSESFPNPEdWLTARTNFARSLAVYSVIGYILGLGDRHPGNILIdR 1958

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  925 DDGQLFHIDFGHFLDHKKKKFGYKrERVPFVLTQDFLIVISKGAQECTktreferFQEMCYKAYLAIRQHANLFINLFSM 1004
Cdd:COG5032   1959 SSGHVIHIDFGFILFNAPGRFPFP-EKVPFRLTRNIVEAMGVSGVEGS-------FRELCETAFRALRKNADSLMNVLEL 2030

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|...
gi 1044420535 1005 MLGS------GMPELQ--SFDDIAYIRKTLALDKTEQEALEYF 1039
Cdd:COG5032   2031 FVRDpliewrRLPCFReiQNNEIVNVLERFRLKLSEKDAEKFV 2073
PI3K_p85B smart00143
PI3-kinase family, p85-binding domain; Region of p110 PI3K that binds the p85 subunit.
 31-108 1.10e-34

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


Pssm-ID: 197539  Cd Length: 78  Bit Score: 126.83  E-value: 1.10e-34
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1044420535    31 IVTLECLREATLVTIKHELFKEARKYPLHQLLQDESSYIFVSVTQEAEREEFFDETRRLCDLRLFQPFLKVIEPVGNR 108
Cdd:smart00143    1 LVTLRVLREATLSTIKHELFKQARKMPLGQLLQDESSYIFVSVNQTAEIEEFFDETRRLSDLRLFFPFLKLIEPVGNR 78
PI3K_p85B pfam02192
PI3-kinase family, p85-binding domain;
34-107 1.11e-33

PI3-kinase family, p85-binding domain;


Pssm-ID: 460483  Cd Length: 74  Bit Score: 123.78  E-value: 1.11e-33
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1044420535   34 LECLREATLVTIKHELFKEARKYPLHQLLQDESSYIFVSVTQEAEREEFFDETRRLCDLRLFQPFLKVIEPVGN 107
Cdd:pfam02192    1 LRVSRNATLSEIKEELWEEAKKYPLYYLLKDPQSYVFTCINQTAEIEELYDETRRLCDVRPFFPILKLVEREGD 74
PI3Ka_III cd00870
Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is ...
 520-676 1.82e-32

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: 123.98  E-value: 1.82e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  520 DNELRENDKE--QLRAICTRDPLSEITEQEKDFLWSHRHYCVTIPEILPKLLLSVKWNSRDEVAQMYCLVKDWPPIKPEQ 597
Cdd:cd00870      1 DKDLKPNSKErkELNKILKYPPTTKLTDEEKDLIWKFRFYLTNNKKALTKFLKSVNWSDEQEVKQALELMPKWAKIDIED 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  598 AMELLDCNYPDPMVRGFAVRCLEKyLTDDKLSQYLIQLVQVLKYEQY-------LDNLLVRFLLKKALTNQRIGHFFFWH 670
Cdd:cd00870     81 ALELLSPYFTNPVVRKYAVSRLKL-ASDEELLLYLLQLVQALKYENLdlsplprLDSPLADFLIERALKNPKLANFLYWY 159


                   ....*.
gi 1044420535  671 LKSEMH 676
Cdd:cd00870    160 LKVELE 165
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 322-418 4.29e-29

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 111.67  E-value: 4.29e-29
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535   322 TSTKSLWVINSALRIKILCATYVNVN-IRDIDKIYVRTGIYHGGEPLCDNVNTQRVPCSNPR-WSEWLNYDIYIPDLPRA 399
Cdd:smart00142    1 VKIESLWDCDRNLVITIALIHGIPLNwSRDYSDLYVEIQLYHGGKLLCLPVSTSYKPFFPSVkWNEWLTFPIQISDLPRE 80

                            90       100
                    ....*....|....*....|
gi 1044420535   400 ARLCLSICSVKGR-KGAKEE 418
Cdd:smart00142   81 ARLCITIYAVKNPsKGSEFG 100
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 173-292 1.14e-27

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


Pssm-ID: 197540  Cd Length: 108  Bit Score: 108.18  E-value: 1.14e-27
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535   173 SSPELPKHIYNKLDKGQIIVVIWVIvspnNDKQKYTLKINHDCVPEQVIAEAIRKKtRSMLLSSEQLKLcvleyqgKYIL 252
Cdd:smart00144    1 TSPSVPEPLPLKTIANKILIVVHLE----KDQQTKTLKVNPNCTPDSVLAQAFTKM-LSLHDQVDPTSE-------DYIL 68

                            90       100       110       120
                    ....*....|....*....|....*....|....*....|
gi 1044420535   253 KVCGCDEYFLEKYPLSQYKYIRSCIMLGRMPNLMLMAKES 292
Cdd:smart00144   69 KVCGRDEYLLGDHPLGSFEYIRNCLKNGTEPHLVLMTLSA 108
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 173-292 1.94e-25

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


Pssm-ID: 395642  Cd Length: 106  Bit Score: 101.60  E-value: 1.94e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  173 SSPELPKHIYnKLDKGQIIVVIWVIvspnNDKQKYTLKINHDCVPEQVIAEAIRKKtRSMLLSSEQlklcvleyQGKYIL 252
Cdd:pfam00794    1 ASTVSPEPLP-KLINNKLLISVHLE----GDQMTKTFTCNPNSTPGSLIAQALTKK-LSVHTQGDV--------TDDYVL 66

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|
gi 1044420535  253 KVCGCDEYFLEKYPLSQYKYIRSCIMLGRMPNLMLMAKES 292
Cdd:pfam00794   67 KVCGRDEYLLGDHPLGQFEYIRNCLKSGREPHLTLVEQSS 106
PIKKc_DNA-PK cd05172
Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, ...
 800-961 7.51e-20

Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, containing the Ku70/80 subunit, and a catalytic subunit, which contains a NUC194 domain of unknown function, a FAT (FRAP, ATM and TRRAP) domain, a catalytic domain, and a FATC domain at the C-terminus. It is part of a multi-component system involved in non-homologous end joining (NHEJ), a process of repairing double strand breaks (DSBs) by joining together two free DNA ends of little homology. DNA-PK functions as a molecular sensor for DNA damage that enhances the signal via phosphorylation of downstream targets. It may also act as a protein scaffold that aids the localization of DNA repair proteins to the site of DNA damage. DNA-PK also plays a role in the maintenance of telomeric stability and the prevention of chromosomal end fusion. DNA-PK is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The DNA-PK catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270716 [Multi-domain]  Cd Length: 235  Bit Score: 89.94  E-value: 7.51e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  800 IFKNGDDLRQDMLTLQIIRIMENIWQN----QGLDLRMLPYGCLSIGDCVGLIEVVRNSHTIMQIQCKGGLKGALQFNSH 875
Cdd:cd05172     33 LVKGGEDLRQDQRIQQLFDVMNNILASdpacRQRRLRIRTYQVIPMTSRLGLIEWVDNTTPLKEILENDLLRRALLSLAS 112

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  876 TLHQWLKDKNKgeiydaaidlFTRSCAGYCVATFILGIGDRHNSNIMV-KDDGQLFHIDFGHfldhkkkKFGYKR----- 949
Cdd:cd05172    113 SPEAFLALRSN----------FARSLAAMSICGYILGIGDRHLSNFLVdLSTGRLIGIDFGH-------AFGSATqflpi 175

                          170
                   ....*....|...
gi 1044420535  950 -ERVPFVLTQDFL 961
Cdd:cd05172    176 pELVPFRLTRQLL 188
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
 767-1006 1.14e-19

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: 88.87  E-value: 1.14e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  767 EECRIMSSAKRPLWLNWENPDiMSELLFqnneiIFKNGDDLRQDMLTLQIIRIM----ENIWQNQGLDLRMLPYGCLSIG 842
Cdd:cd05164      6 PRVRILASLQKPKKITILGSD-GKEYPF-----LVKGDDDLRKDERVMQLFQLLntllEKDKETRKRNLTIRTYSVVPLS 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  843 DCVGLIEVVRNSHTimqiqCKGGLKGALQFNSHTLHQWLkdknkgeiydAAIDLFTRSCAGYCVATFILGIGDRHNSNIM 922
Cdd:cd05164     80 SQSGLIEWVDNTTT-----LKPVLKKWFNETFPDPTQWY----------EARSNYTKSTAVMSMVGYIIGLGDRHLENIL 144

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  923 V-KDDGQLFHIDFGHFLdHKKKKFGyKRERVPFVLTQDflIVISKGAQECTKTreferFQEMCYKAYLAIRQHANLFINL 1001
Cdd:cd05164    145 IdTKTGEVVHIDFGMIF-NKGKTLP-VPEIVPFRLTRN--IINGMGPTGVEGL-----FRKSCEQVLRVFRKHKDKLITF 215


                   ....*
gi 1044420535 1002 FSMML 1006
Cdd:cd05164    216 LDTFL 220
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 352-487 4.47e-19

C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. Class II PIK3s act downstream of receptors for growth factors, integrins, and chemokines. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 175979  Cd Length: 171  Bit Score: 85.49  E-value: 4.47e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  352 DKIYVRTGIYHGGEPLCDNVNTQRVPCSN-----PRWSEWLNYDIYIPDLPRAARLCLSI---------CSVKGRKGAKe 417
Cdd:cd04012     29 EDFYLSCSLYHGGRLLCSPVTTKPVKITKsffprVVWDEWIEFPIPVCQLPRESRLVLTLygttsspdgGSNKQRMGPE- 107

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  418 ehcPLAWGNINLFDYTDTLVSGKMALNLWPVPHgleDLLNPIGVTGSNPNKETPCLELEFDWFSSVVKFP 487
Cdd:cd04012    108 ---ELGWVSLPLFDFRGVLRQGSLLLGLWPPSK---DNPLGPAPPPLFEQPDRVILQIDFPSSAFDVIFP 171
C2_PI3K_class_I_gamma cd08399
C2 domain present in class I gamma phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 324-470 6.08e-17

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


Pssm-ID: 176044  Cd Length: 178  Bit Score: 79.96  E-value: 6.08e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  324 TKSLWVINSALRIKILCATYVNVNIRDIDKIYVRTGIYHGGEPLCDNVNTQRVPCSNPRWSEWLNYDIYIPDLPRAARLC 403
Cdd:cd08399      2 TVSLWDCDRKFRVKILGIDIPVLPRNTDLTVFVEANIQHGQQVLCQRRTSPKPFTEEVLWNTWLEFDIKIKDLPKGALLN 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  404 LSICSVKGRKGA------------KEEHCPLAWGNINLFDYTDTLVSGKMALNLWPVPHGLEDL--LNPIGVTG-SNPNK 468
Cdd:cd08399     82 LQIYCGKAPALSskksaespssesKGKHQLLYYVNLLLIDHRFLLRTGEYVLHMWQISGKGEDQgsVNADKLTSaTNPDK 161


                   ..
gi 1044420535  469 ET 470
Cdd:cd08399    162 EN 163
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 767-958 9.62e-17

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: 80.63  E-value: 9.62e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  767 EECRIMSSAKRPLWLNWENPDimsellfqNNEIIF--KNGDDLRQDM----LTLQIIRIMENIWQNQGLDLRMLPYGCLS 840
Cdd:cd00892      6 DEVEIMPSLQKPKKITLVGSD--------GKKYPFlcKPKDDLRKDArmmeFNTLINRLLSKDPESRRRNLHIRTYAVIP 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  841 IGDCVGLIEVVRNSHTIMQIqckgglkgALQFNSHTLHQWLKdKNKGEIYD--AAIDLFTRSCAGYCVATFILGIGDRHN 918
Cdd:cd00892     78 LNEECGIIEWVPNTVTLRSI--------LSTLYPPVLHEWFL-KNFPDPTAwyEARNNYTRSTAVMSMVGYILGLGDRHG 148

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1044420535  919 SNIMV-KDDGQLFHIDFGHFLDhKKKKFGYKrERVPFVLTQ 958
Cdd:cd00892    149 ENILFdSTTGDVVHVDFDCLFD-KGLTLEVP-ERVPFRLTQ 187
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
 800-961 1.18e-15

Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA double strand breaks (DSBs) caused by radiation. It is activated at the site of a DSB and phosphorylates key substrates that trigger pathways that regulate DNA repair and cell cycle checkpoints at the G1/S, S phase, and G2/M transition. Patients with the human genetic disorder Ataxia telangiectasia (A-T), caused by truncating mutations in ATM, show genome instability, increased cancer risk, immunodeficiency, compromised mobility, and neurodegeneration. A-T displays clinical heterogeneity, which is correlated to the degree of retained ATM activity. ATM contains a FAT (FRAP, ATM and TRRAP) domain, a catalytic domain, and a FATC domain at the C-terminus. It is a member of the phosphoinositide 3-kinase-related protein kinase (PIKK) subfamily. PIKKs have intrinsic serine/threonine kinase activity and are distinguished from other PKs by their unique catalytic domain, similar to that of lipid PI3K, and their large molecular weight (240-470 kDa). The ATM catalytic domain subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as the typical serine/threonine/tyrosine protein kinases (PKs), aminoglycoside phosphotransferase, choline kinase, and RIO kinases.


Pssm-ID: 270715 [Multi-domain]  Cd Length: 282  Bit Score: 78.74  E-value: 1.18e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  800 IFKNGDDLRQDmltlqiiRIMENIWQ--NQGL---------DLRMLPYGCLSIGDCVGLIEVVRNSHTIMQIQCKGGLKG 868
Cdd:cd05171     33 LVKGGDDLRQD-------AVMEQVFElvNQLLkrdketrkrKLRIRTYKVVPLSPRSGVLEFVENTIPLGEYLVGASSKS 105

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  869 AL-------QFNSHTLHQWLKDKNKG----------EIYD---------------AAIDLF------TRSCAGYCVATFI 910
Cdd:cd05171    106 GAharyrpkDWTASTCRKKMREKAKAsaeerlkvfdEICKnfkpvfrhfflekfpDPSDWFerrlayTRSVATSSIVGYI 185

                          170       180       190       200       210
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1044420535  911 LGIGDRHNSNIMV-KDDGQLFHIDFGHFLDhkkkkFGyKR----ERVPFVLTQDFL 961
Cdd:cd05171    186 LGLGDRHLNNILIdQKTGELVHIDLGIAFE-----QG-KLlpipETVPFRLTRDIV 235
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 771-957 3.72e-12

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: 67.89  E-value: 3.72e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  771 IMSSAKRP--LWLNWENPDIMSELLfqnneiifKNGDDLRQDMLTLQIIR----IMENIWQNQGLDLRMLPYGCLSIGDC 844
Cdd:cd05169     10 VITSKQRPrkLTIVGSDGKEYKFLL--------KGHEDLRLDERVMQLFGlvntLLKNDSETSRRNLSIQRYSVIPLSPN 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  845 VGLIEVVRNSHTIMQ--------------IQCKGGLKGALQFNSHTLHQ---------------------WLKDKNkGEI 889
Cdd:cd05169     82 SGLIGWVPGCDTLHSlirdyrekrkiplnIEHRLMLQMAPDYDNLTLIQkvevfeyalentpgddlrrvlWLKSPS-SEA 160

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1044420535  890 YDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDD-GQLFHIDFGhflD-----HKKKKFgykRERVPFVLT 957
Cdd:cd05169    161 WLERRTNFTRSLAVMSMVGYILGLGDRHPSNIMLDRLtGKVIHIDFG---DcfevaMHREKF---PEKVPFRLT 228
PI4Ka cd00871
Phosphoinositide 4-kinase(PI4K), accessory domain (PIK domain); PIK domain is conserved in PI3 ...
 537-675 1.24e-11

Phosphoinositide 4-kinase(PI4K), accessory domain (PIK domain); PIK domain is conserved in PI3 and PI4-kinases. Its role is unclear but it has been suggested to be involved in substrate presentation. PI4K phosphorylates hydroxylgroup at position 4 on the inositol ring of phosphoinositide, the first commited step in the phosphatidylinositol cycle.


Pssm-ID: 238443  Cd Length: 175  Bit Score: 64.30  E-value: 1.24e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  537 RDPLSEITEQEKDFLWSHRHYCVTIPEILPKLllsVKWNSRDEVAQMYCLVKDWPPIKPEQAMELLDCNYP-DPMVRGFA 615
Cdd:cd00871     15 RFPNSKLKSEVTRLVRKHPLAVVKIPEALPFL---VTGKSVDENSPDLKYLLYWAPVSPVQALSLFTPQYPgHPLVLQYA 91

                           90       100       110       120       130       140
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  616 VRCLEKYLTDDKLSqYLIQLVQVLKYEQylDNLLVRFLLKKALTNQRIGHFFFWHLKSEM 675
Cdd:cd00871     92 VRVLESYPVETVFF-YIPQIVQALRYDK--MGYVEEYILETAKRSQLFAHQIIWNMQTNC 148
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
 789-935 6.70e-09

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: 55.53  E-value: 6.70e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  789 MSELLFQNNEIIFKNGDD--------LRQDMLTLQIIRIMEniwqnqgldlrMLPYGCLSIGDC----VGLIEVVRnsht 856
Cdd:cd13968     11 WAEGECTTIGVAVKIGDDvnneegedLESEMDILRRLKGLE-----------LNIPKVLVTEDVdgpnILLMELVK---- 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  857 imqiqcKGGLKGALQfnshtlhqwlkdknKGEIYDAAIDLFTRSCAGYCVATFI--LGIGDRHNSNIMVKDDGQLFHIDF 934
Cdd:cd13968     76 ------GGTLIAYTQ--------------EEELDEKDVESIMYQLAECMRLLHSfhLIHRDLNNDNILLSEDGNVKLIDF 135


                   .
gi 1044420535  935 G 935
Cdd:cd13968    136 G 136
C2_PI3K_class_III cd08397
C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 354-447 7.36e-09

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: 55.72  E-value: 7.36e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1044420535  354 IYVRTGIYHGGEPLCDNVNTQRVPCSNPR-WSEWLNYDIYIPDLPRAARLCLSICSVKGrkGAKEehCPLAWGNINLFDY 432
Cdd:cd08397     32 LFVTCQVFDDGKPLTLPVQTSYKPFKNRRnWNEWLTLPIKYSDLPRNSQLAITIWDVSG--TGKA--VPFGGTTLSLFNK 107

                           90
                   ....*....|....*
gi 1044420535  433 TDTLVSGKMALNLWP 447
Cdd:cd08397    108 DGTLRRGRQKLRVWP 122
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
 897-960 1.78e-05

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: 48.02  E-value: 1.78e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1044420535  897 FTRSCAGYCVATFILGIGDRHNSNIMVK-DDGQLFHIDFGHFLDhKKKKFgykR--ERVPFVLTQDF 960
Cdd:cd05170    194 FARSLAVMSMIGYIIGLGDRHLDNILVDlSTGEVVHIDYNVCFE-KGKRL---RvpEKVPFRLTQNI 256
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

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