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Conserved domains on  [gi|1207137159|ref|XP_021323495|]
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phosphatidylinositol 4-phosphate 3-kinase C2 domain-containing subunit alpha isoform X1 [Danio rerio]

Protein Classification

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PKc_like super family cl21453
Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the ...
 1045-1397 0e+00

Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the catalytic domains of serine/threonine-specific and tyrosine-specific protein kinases. It also includes RIO kinases, which are atypical serine protein kinases, aminoglycoside phosphotransferases, and choline kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to hydroxyl groups in specific substrates such as serine, threonine, or tyrosine residues of proteins.


The actual alignment was detected with superfamily member cd05176:

Pssm-ID: 473864 [Multi-domain]  Cd Length: 353  Bit Score: 722.54  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1045 RAELEKQTRLVQLLGALAEKVRQASSSTRQVVLLEGLERVQSFFQKNSCRLPISPSLVAKELNIKVCSFFNSNAVPLKIA 1124
Cdd:cd05176      1 REELEKQTRLVQLLGRVAEKVRQASGSARQVALQDGMERVQSFFQKNKCRLPLSPSLVAKELNIKACSFFSSNAVPLKVA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1125 LVNADPLGDEINVMFKVGEDLRQDMLALQMIRIMDRIWLQEGLDLRIVNFKCISTGKDKGMVELVPSSETLRKIQVEYGV 1204
Cdd:cd05176     81 LVNADPLGEEINVMFKVGEDLRQDMLALQMIKIMDKIWLQEGLDLRMVIFKCLSTGKDRGMVELVPSSDTLRKIQVEYGV 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1205 TGSFKDKPLAEWLRKYNPAEDEYEKASENFIYTCAGCCVATYILGICDRHNDNIMLRSTGHMFHIDFGKFLGHAQMIGSF 1284
Cdd:cd05176    161 TGSFKDKPLAEWLRKYNPSEEEYEKASENFIYSCAGCCVATYVLGICDRHNDNIMLRSTGHMFHIDFGKFLGHAQMFGSF 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1285 KRDRAPFVLTSDMAYVINGGERPTSRFQLFVDLCSQAYNLIRKHSNLFLNLLSLMTQSGLPELTGVQDLKYVYDALQPQT 1364
Cdd:cd05176    241 KRDRAPFVLTSDMAYVINGGEKPTIRFQLFVDLCCQAYNLIRKHTNLFLNLLSLMLSSGLPELTGIQDLKYVFDALQPQT 320

                          330       340       350
                   ....*....|....*....|....*....|...
gi 1207137159 1365 TDAEATIFFTRLIESSLGSVATKFNFFIHNLAQ 1397
Cdd:cd05176    321 TDAEATIFFTRLIESSLGSVATKFNFFIHNLAQ 353
PX_PI3K_C2_alpha cd07289
The phosphoinositide binding Phox Homology Domain of the Alpha Isoform of Class II ...
 1428-1536 2.81e-74

The phosphoinositide binding Phox Homology Domain of the Alpha Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II alpha isoform, PI3K-C2alpha, plays key roles in clathrin assembly and clathrin-mediated membrane trafficking, insulin signaling, vascular smooth muscle contraction, and the priming of neurosecretory granule exocytosis. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


:

Pssm-ID: 132822  Cd Length: 109  Bit Score: 241.76  E-value: 2.81e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1428 DASVFSFQKRYNPDKHYTYVIRILREGQSEPQFVFRTFDEFQELHNKLTILFQLWKLPGFPSKMVLGRTHIKDVASKRKV 1507
Cdd:cd07289      1 EVSVFTYHKRYNPDKHYIYVVRILREGQIEPSFVFRTFDEFQELHNKLSILFPLWKLPGFPNKMVLGRTHIKDVAAKRKV 80

                           90       100
                   ....*....|....*....|....*....
gi 1207137159 1508 ELNSYVHNLMRSSTEVAQCDLIYTFFHPI 1536
Cdd:cd07289     81 ELNSYIQSLMNSSTEVAECDLVYTFFHPL 109
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 681-852 1.14e-71

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: 236.87  E-value: 1.14e-71
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  681 KEASGTTEHLQFTLFAVHGIPATWVSSFEKYYLMCALTHNNRNLFKPVQSKKVGTYKSFFYHIKWDELINFPISVSLLPL 760
Cdd:cd04012      1 REASTVTDLLSVTVSSLHRIPPTWVQSFEDFYLSCSLYHGGRLLCSPVTTKPVKITKSFFPRVVWDEWIEFPIPVCQLPR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  761 EAMLSLSLYGVLSQNANNspdSNKQRKGPELLGKVSMPLFDFRRVLSRGSKLLSLWTSPQALQPGAAGKGRNPTEK-IIL 839
Cdd:cd04012     81 ESRLVLTLYGTTSSPDGG---SNKQRMGPEELGWVSLPLFDFRGVLRQGSLLLGLWPPSKDNPLGPAPPPLFEQPDrVIL 157

                          170
                   ....*....|...
gi 1207137159  840 QVDFPSPAVDVLY 852
Cdd:cd04012    158 QIDFPSSAFDVIF 170
C2B_PI3K_class_II cd08381
C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are ...
 1565-1686 1.67e-70

C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


:

Pssm-ID: 176027 [Multi-domain]  Cd Length: 122  Bit Score: 231.80  E-value: 1.67e-70
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1565 EGEVKLSVSYRNSTLFIMVMHIKDLMSNDGADPNPYVKTYLLPDPHKTSKRKTKIARKTRNPTFNEMLVYSGYSKETLKQ 1644
Cdd:cd08381      1 GGQVKLSISYKNGTLFVMVMHAKNLPLLDGSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDGLPVEDLQQ 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1207137159 1645 RELQLSVLSAESLRENCYLGGITLCLKDFDLSRETVKWYKLT 1686
Cdd:cd08381     81 RVLQVSVWSHDSLVENEFLGGVCIPLKKLDLSQETEKWYPLG 122
PI3Ka super family cl00271
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 872-1038 3.70e-65

Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in PI3 and PI4-kinases. Its role is unclear, but it has been suggested to be involved in substrate presentation. Phosphoinositide 3-kinases play an important role in a variety of fundamental cellular processes and can be divided into three main classes, defined by their substrate specificity and domain architecture.


The actual alignment was detected with superfamily member cd00869:

Pssm-ID: 412275  Cd Length: 169  Bit Score: 218.48  E-value: 3.70e-65
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  872 DDRSEIEKLCARASTFGLSRADRQLLWDQRYYCREYEYSLPKILASAPSWDWGSMGEIHALLHHWPALSPVSALELLESK 951
Cdd:cd00869      2 ETQEKLLDLIQKQSTYTLSTEDKDLLWEKRLYCTNEPNALPLVLASAPSWDWANLMDVYQLLHQWAPLRPLIALELLLPK 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  952 FADTEVRKVAVSWIQSSSDDELADYLPQLVQAVKFECHLNNALVKFLLSRALGNVNIAHYLYWLLRDAVQDPAFGQRYER 1031
Cdd:cd00869     82 FPDQEVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALDDCYFSSAYQD 161


                   ....*..
gi 1207137159 1032 ILCVLLC 1038
Cdd:cd00869    162 LGAALRC 168
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 420-507 1.14e-26

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: 105.84  E-value: 1.14e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  420 GGSVKVSIEISDSQQPVTFTCDVTSPVDLLIMQALCWVHDDLNQVDI-NSYVLKVCGQEEVLQNKHSLGSHEYVQNCRKW 498
Cdd:pfam00794   14 NNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVtDDYVLKVCGRDEYLLGDHPLGQFEYIRNCLKS 93


                   ....*....
gi 1207137159  499 ESEIKLQLL 507
Cdd:pfam00794   94 GREPHLTLV 102
DUF5585 super family cl39316
Family of unknown function (DUF5585); This is a family of unknown function found in chordata.
 140-243 3.77e-04

Family of unknown function (DUF5585); This is a family of unknown function found in chordata.


The actual alignment was detected with superfamily member pfam17823:

Pssm-ID: 465521 [Multi-domain]  Cd Length: 506  Bit Score: 44.95  E-value: 3.77e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  140 HAFNPSSFHWTPTPTHAQTPIFPSAPFAKPPCSFQNGFSPAMSPFIPPTPFLSFT---PIQPPAALVYSQPAVTPEMAKL 216
Cdd:pfam17823  276 HARRLSPAKHMPSDTMARNPAAPMGAQAQGPIIQVSTDQPVHNTAGEPTPSPSNTtlePNTPKSVASTNLAVVTTTKAQA 355

                           90       100
                   ....*....|....*....|....*..
gi 1207137159  217 FDKIASTSEYLKNGRSSSMETESASVK 243
Cdd:pfam17823  356 KEPSASPVPVLHTSMIPEVEATSPTTQ 382
 
Name Accession Description Interval E-value
PI3Kc_C2_alpha cd05176
Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 1045-1397 0e+00

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: 722.54  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1045 RAELEKQTRLVQLLGALAEKVRQASSSTRQVVLLEGLERVQSFFQKNSCRLPISPSLVAKELNIKVCSFFNSNAVPLKIA 1124
Cdd:cd05176      1 REELEKQTRLVQLLGRVAEKVRQASGSARQVALQDGMERVQSFFQKNKCRLPLSPSLVAKELNIKACSFFSSNAVPLKVA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1125 LVNADPLGDEINVMFKVGEDLRQDMLALQMIRIMDRIWLQEGLDLRIVNFKCISTGKDKGMVELVPSSETLRKIQVEYGV 1204
Cdd:cd05176     81 LVNADPLGEEINVMFKVGEDLRQDMLALQMIKIMDKIWLQEGLDLRMVIFKCLSTGKDRGMVELVPSSDTLRKIQVEYGV 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1205 TGSFKDKPLAEWLRKYNPAEDEYEKASENFIYTCAGCCVATYILGICDRHNDNIMLRSTGHMFHIDFGKFLGHAQMIGSF 1284
Cdd:cd05176    161 TGSFKDKPLAEWLRKYNPSEEEYEKASENFIYSCAGCCVATYVLGICDRHNDNIMLRSTGHMFHIDFGKFLGHAQMFGSF 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1285 KRDRAPFVLTSDMAYVINGGERPTSRFQLFVDLCSQAYNLIRKHSNLFLNLLSLMTQSGLPELTGVQDLKYVYDALQPQT 1364
Cdd:cd05176    241 KRDRAPFVLTSDMAYVINGGEKPTIRFQLFVDLCCQAYNLIRKHTNLFLNLLSLMLSSGLPELTGIQDLKYVFDALQPQT 320

                          330       340       350
                   ....*....|....*....|....*....|...
gi 1207137159 1365 TDAEATIFFTRLIESSLGSVATKFNFFIHNLAQ 1397
Cdd:cd05176    321 TDAEATIFFTRLIESSLGSVATKFNFFIHNLAQ 353
PX_PI3K_C2_alpha cd07289
The phosphoinositide binding Phox Homology Domain of the Alpha Isoform of Class II ...
 1428-1536 2.81e-74

The phosphoinositide binding Phox Homology Domain of the Alpha Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II alpha isoform, PI3K-C2alpha, plays key roles in clathrin assembly and clathrin-mediated membrane trafficking, insulin signaling, vascular smooth muscle contraction, and the priming of neurosecretory granule exocytosis. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


Pssm-ID: 132822  Cd Length: 109  Bit Score: 241.76  E-value: 2.81e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1428 DASVFSFQKRYNPDKHYTYVIRILREGQSEPQFVFRTFDEFQELHNKLTILFQLWKLPGFPSKMVLGRTHIKDVASKRKV 1507
Cdd:cd07289      1 EVSVFTYHKRYNPDKHYIYVVRILREGQIEPSFVFRTFDEFQELHNKLSILFPLWKLPGFPNKMVLGRTHIKDVAAKRKV 80

                           90       100
                   ....*....|....*....|....*....
gi 1207137159 1508 ELNSYVHNLMRSSTEVAQCDLIYTFFHPI 1536
Cdd:cd07289     81 ELNSYIQSLMNSSTEVAECDLVYTFFHPL 109
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 681-852 1.14e-71

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: 236.87  E-value: 1.14e-71
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  681 KEASGTTEHLQFTLFAVHGIPATWVSSFEKYYLMCALTHNNRNLFKPVQSKKVGTYKSFFYHIKWDELINFPISVSLLPL 760
Cdd:cd04012      1 REASTVTDLLSVTVSSLHRIPPTWVQSFEDFYLSCSLYHGGRLLCSPVTTKPVKITKSFFPRVVWDEWIEFPIPVCQLPR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  761 EAMLSLSLYGVLSQNANNspdSNKQRKGPELLGKVSMPLFDFRRVLSRGSKLLSLWTSPQALQPGAAGKGRNPTEK-IIL 839
Cdd:cd04012     81 ESRLVLTLYGTTSSPDGG---SNKQRMGPEELGWVSLPLFDFRGVLRQGSLLLGLWPPSKDNPLGPAPPPLFEQPDrVIL 157

                          170
                   ....*....|...
gi 1207137159  840 QVDFPSPAVDVLY 852
Cdd:cd04012    158 QIDFPSSAFDVIF 170
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 1137-1351 1.60e-70

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: 236.43  E-value: 1.60e-70
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  1137 VMFKVGEDLRQDMLALQMIRIMDRIWLQE----GLDLRIVNFKCISTGKDKGMVELVPSSETLRKIQVEY---------- 1202
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  1203 ---------------GVTGSFKDKPLAEWLRKYNPAEDE-YEKASENFIYTCAGCCVATYILGICDRHNDNIMLRSTGHM 1266
Cdd:smart00146   81 rsqtatrlkklelflEATGKFPDPVLYDWFTKKFPDPSEdYFEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  1267 FHIDFGKFLGHAQMIGSFKrDRAPFVLTSDMAYVINggerPTSRFQLFVDLCSQAYNLIRKHSNLFLNLLSLMTQSGLPE 1346
Cdd:smart00146  161 FHIDFGFILGNGPKLFGFP-ERVPFRLTPEMVDVMG----DSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLPD 235


                    ....*
gi 1207137159  1347 LTGVQ 1351
Cdd:smart00146  236 WRSGK 240
C2B_PI3K_class_II cd08381
C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are ...
 1565-1686 1.67e-70

C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176027 [Multi-domain]  Cd Length: 122  Bit Score: 231.80  E-value: 1.67e-70
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1565 EGEVKLSVSYRNSTLFIMVMHIKDLMSNDGADPNPYVKTYLLPDPHKTSKRKTKIARKTRNPTFNEMLVYSGYSKETLKQ 1644
Cdd:cd08381      1 GGQVKLSISYKNGTLFVMVMHAKNLPLLDGSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDGLPVEDLQQ 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1207137159 1645 RELQLSVLSAESLRENCYLGGITLCLKDFDLSRETVKWYKLT 1686
Cdd:cd08381     81 RVLQVSVWSHDSLVENEFLGGVCIPLKKLDLSQETEKWYPLG 122
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
 872-1038 3.70e-65

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: 218.48  E-value: 3.70e-65
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  872 DDRSEIEKLCARASTFGLSRADRQLLWDQRYYCREYEYSLPKILASAPSWDWGSMGEIHALLHHWPALSPVSALELLESK 951
Cdd:cd00869      2 ETQEKLLDLIQKQSTYTLSTEDKDLLWEKRLYCTNEPNALPLVLASAPSWDWANLMDVYQLLHQWAPLRPLIALELLLPK 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  952 FADTEVRKVAVSWIQSSSDDELADYLPQLVQAVKFECHLNNALVKFLLSRALGNVNIAHYLYWLLRDAVQDPAFGQRYER 1031
Cdd:cd00869     82 FPDQEVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALDDCYFSSAYQD 161


                   ....*..
gi 1207137159 1032 ILCVLLC 1038
Cdd:cd00869    162 LGAALRC 168
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 1134-1348 6.62e-65

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: 220.66  E-value: 6.62e-65
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1134 EINVMFKVGEDLRQDMLALQMIRIMDRIWLQEGLDL-RIVNFKCISTGKDKGMVELVPSSETLRKIQVEYG-----VTGS 1207
Cdd:pfam00454    1 GYGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEYGengvpPTAM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1208 FKDK-----------------------PLAEWLRKYNPAEDEYEKASENFIYTCAGCCVATYILGICDRHNDNIML-RST 1263
Cdd:pfam00454   81 VKILhsalnypklklefesrislppkvGLLQWFVKKSPDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTT 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1264 GHMFHIDFGKFLGHAQMIGSFKrDRAPFVLTSDMAYVINggerPTSRFQLFVDLCSQAYNLIRKHSNLFLNLLSLMTQSG 1343
Cdd:pfam00454  161 GKLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAMG----PSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVADG 235


                   ....*
gi 1207137159 1344 LPELT 1348
Cdd:pfam00454  236 LPDWS 240
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 868-1049 1.77e-55

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: 191.32  E-value: 1.77e-55
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159   868 PLDQDDRSEIEKLCARASTFGLSRADRQLLWDQRYYC-REYEYSLPKILaSAPSWDWGS-MGEIHALLHHWPALSPVSAL 945
Cdd:smart00145    2 PLDIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYlTNNPKALPKFL-LSVKWSDADeVAQALSLLLSWAPLDPEDAL 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159   946 ELLESKFADTEVRKVAVSWIQSSSDDELADYLPQLVQAVKFECHLNNALVKFLLSRALGNVNIAHYLYWLLRDAVQDPAF 1025
Cdd:smart00145   81 ELLDPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHV 160

                           170       180
                    ....*....|....*....|....
gi 1207137159  1026 GQRYERILCVLLCLCGTGLRAELE 1049
Cdd:smart00145  161 SIRFGLLLEAYLRGCGTHLKELLK 184
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 868-1045 6.22e-40

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: 146.71  E-value: 6.22e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  868 PLDQDDRSEIEKLCARASTFGLSRADRQLLWDQRYYCREYEYSLPKILASAPswdWGSMGEIHALLHH---WPALSPVSA 944
Cdd:pfam00613    4 KPNEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYLMLVPKALTKLLLSVK---WSDLSEVAEALSLllkWAPIDPVDA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  945 LELLESKFADTEVRKVAVSWIQSSSDDELADYLPQLVQAVKFECHLNNALVKFLLSRALGNVNIAHYLYWLLRDAVQDPA 1024
Cdd:pfam00613   81 LELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEIHDEE 160

                          170       180
                   ....*....|....*....|.
gi 1207137159 1025 FGQRYERILCVLLCLCGTGLR 1045
Cdd:pfam00613  161 VSPRFGSLLELYLRSCGTSLL 181
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
1137-1384 2.61e-29

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 128.36  E-value: 2.61e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1137 VMFKVGEDLRQDMLALQMIRIMDRIWLQEGL----DLRIVNFKCISTGKDKGMVELVPSSETLRKIQVEY---------- 1202
Cdd:COG5032   1799 FIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGIIEWVPNSDTLHSILREYhkrknisidq 1878

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1203 --------------------GVTGSFKDKPLAEWLRKYNPAEDEYEKASENFIYTCAGCCVATYILGICDRHNDNIML-R 1261
Cdd:COG5032   1879 ekklaarldnlklllkdeffTKATLKSPPVLYDWFSESFPNPEDWLTARTNFARSLAVYSVIGYILGLGDRHPGNILIdR 1958

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1262 STGHMFHIDFGKFLGHAqmIGSFK-RDRAPFVLTSDMAYVI--NGGErptsrfQLFVDLCSQAYNLIRKHSNLFLNLLSL 1338
Cdd:COG5032   1959 SSGHVIHIDFGFILFNA--PGRFPfPEKVPFRLTRNIVEAMgvSGVE------GSFRELCETAFRALRKNADSLMNVLEL 2030

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1207137159 1339 M------TQSGLPELTGVQ--DLKYVYDALQPQTTDAEATIFFTRLIESSLGSV 1384
Cdd:COG5032   2031 FvrdpliEWRRLPCFREIQnnEIVNVLERFRLKLSEKDAEKFVDLLINKSVESL 2084
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 420-507 1.14e-26

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: 105.84  E-value: 1.14e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  420 GGSVKVSIEISDSQQPVTFTCDVTSPVDLLIMQALCWVHDDLNQVDI-NSYVLKVCGQEEVLQNKHSLGSHEYVQNCRKW 498
Cdd:pfam00794   14 NNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVtDDYVLKVCGRDEYLLGDHPLGQFEYIRNCLKS 93


                   ....*....
gi 1207137159  499 ESEIKLQLL 507
Cdd:pfam00794   94 GREPHLTLV 102
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 420-507 5.21e-24

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: 98.17  E-value: 5.21e-24
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159   420 GGSVKVSIEISDSQQPVTFTCDVTSPVDLLIMQALCWVHDDLNQVDINS--YVLKVCGQEEVLQNKHSLGSHEYVQNCRK 497
Cdd:smart00144   15 ANKILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQVDPTSedYILKVCGRDEYLLGDHPLGSFEYIRNCLK 94

                            90
                    ....*....|
gi 1207137159   498 WESEIKLQLL 507
Cdd:smart00144   95 NGTEPHLVLM 104
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 709-843 1.67e-22

Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 domain. Outlier of pfam00168 family.


Pssm-ID: 395640  Cd Length: 136  Bit Score: 94.74  E-value: 1.67e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  709 EKYYLMCALTHNNRNLFKPVQSKkvgtYKSF-FYHIKWDELINFPISVSLLPLEAMLSLSLYGVLSQNANNSPdsnkqrk 787
Cdd:pfam00792    3 EDLYVECQLYHGGKPLCLPVSTR----YVPFsNSSIKWNEWITFPIQISDLPRSARLCITIWDVSGPEKSFVP------- 71

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207137159  788 gpelLGKVSMPLFDFRRVLSRGSKLLSLWTSPQalQPGAAGKGR-NPTEKIILQVDF 843
Cdd:pfam00792   72 ----IGWVNTSLFDKKGILRQGKQKLRLWPSKS--TPGRSNVDEmNRLEKLLKKYER 122
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 678-771 3.27e-22

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 92.79  E-value: 3.27e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159   678 RDSKEASGTTEHLQFTLFAVHGIPATWVSSFEKYYLMCALTHNNRNLFKPVQSkkvgTYKSFFYHIKWDELINFPISVSL 757
Cdd:smart00142    1 VKIESLWDCDRNLVITIALIHGIPLNWSRDYSDLYVEIQLYHGGKLLCLPVST----SYKPFFPSVKWNEWLTFPIQISD 76

                            90
                    ....*....|....
gi 1207137159   758 LPLEAMLSLSLYGV 771
Cdd:smart00142   77 LPREARLCITIYAV 90
PX smart00312
PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function ...
 1437-1534 1.80e-20

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


Pssm-ID: 214610  Cd Length: 105  Bit Score: 88.17  E-value: 1.80e-20
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  1437 RYNPDKHYTYVIRILREGQSEPQFVFRTFDEFQELHNKLTILFQLWKLPGFPSKMVLGRT--HIKDVASKRKVELNSYVH 1514
Cdd:smart00312    6 KIGDGKHYYYVIEIETKTGLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRLnnFSEEFIEKRRRGLEKYLQ 85

                            90       100
                    ....*....|....*....|
gi 1207137159  1515 NLMRSSTEVAQCDLIYTFFH 1534
Cdd:smart00312   86 SLLNHPELINHSEVVLEFLE 105
C2 pfam00168
C2 domain;
1578-1685 1.37e-19

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 85.45  E-value: 1.37e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1578 TLFIMVMHIKDLMSNDGAD-PNPYVKTYLLpdpHKTSKRKTKIARKTRNPTFNEMLVYSGYSKEtlkQRELQLSVLSAES 1656
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNGtSDPYVKVYLL---DGKQKKKTKVVKNTLNPVWNETFTFSVPDPE---NAVLEIEVYDYDR 75

                           90       100
                   ....*....|....*....|....*....
gi 1207137159 1657 LRENCYLGGITLCLKDFDLSRETVKWYKL 1685
Cdd:pfam00168   76 FGRDDFIGEVRIPLSELDSGEGLDGWYPL 104
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 1578-1682 4.96e-15

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


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 72.52  E-value: 4.96e-15
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  1578 TLFIMVMHIKDLMSNDGAD-PNPYVKTYLLPDPHKtsKRKTKIARKTRNPTFNEMLVYSGYSKETlkqRELQLSVLSAES 1656
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGkSDPYVKVSLDGDPKE--KKKTKVVKNTLNPVWNETFEFEVPPPEL---AELEIEVYDKDR 75

                            90       100
                    ....*....|....*....|....*.
gi 1207137159  1657 LRENCYLGGITLCLKDFDLSRETVKW 1682
Cdd:smart00239   76 FGRDDFIGQVTIPLSDLLLGGRHEKL 101
PX pfam00787
PX domain; PX domains bind to phosphoinositides.
 1451-1535 2.73e-14

PX domain; PX domains bind to phosphoinositides.


Pssm-ID: 459940  Cd Length: 84  Bit Score: 69.58  E-value: 2.73e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1451 LREGQSEPQFVFRTFDEFQELHNKLTILFQLWKLPGFPSKMVLGRTHiKDVASKRKVELNSYVHNLMRSStEVAQCDLIY 1530
Cdd:pfam00787    1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLGRYN-EEFIEKRRKGLEQYLQRLLQHP-ELRNSEVLL 78


                   ....*
gi 1207137159 1531 TFFHP 1535
Cdd:pfam00787   79 EFLES 83
DUF5585 pfam17823
Family of unknown function (DUF5585); This is a family of unknown function found in chordata.
 140-243 3.77e-04

Family of unknown function (DUF5585); This is a family of unknown function found in chordata.


Pssm-ID: 465521 [Multi-domain]  Cd Length: 506  Bit Score: 44.95  E-value: 3.77e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  140 HAFNPSSFHWTPTPTHAQTPIFPSAPFAKPPCSFQNGFSPAMSPFIPPTPFLSFT---PIQPPAALVYSQPAVTPEMAKL 216
Cdd:pfam17823  276 HARRLSPAKHMPSDTMARNPAAPMGAQAQGPIIQVSTDQPVHNTAGEPTPSPSNTtlePNTPKSVASTNLAVVTTTKAQA 355

                           90       100
                   ....*....|....*....|....*..
gi 1207137159  217 FDKIASTSEYLKNGRSSSMETESASVK 243
Cdd:pfam17823  356 KEPSASPVPVLHTSMIPEVEATSPTTQ 382
Amelogenin smart00818
Amelogenins, cell adhesion proteins, play a role in the biomineralisation of teeth; They seem ...
 137-207 4.62e-04

Amelogenins, cell adhesion proteins, play a role in the biomineralisation of teeth; They seem to regulate formation of crystallites during the secretory stage of tooth enamel development and are thought to play a major role in the structural organisation and mineralisation of developing enamel. The extracellular matrix of the developing enamel comprises two major classes of protein: the hydrophobic amelogenins and the acidic enamelins. Circular dichroism studies of porcine amelogenin have shown that the protein consists of 3 discrete folding units: the N-terminal region appears to contain beta-strand structures, while the C-terminal region displays characteristics of a random coil conformation. Subsequent studies on the bovine protein have indicated the amelogenin structure to contain a repetitive beta-turn segment and a "beta-spiral" between Gln112 and Leu138, which sequester a (Pro, Leu, Gln) rich region. The beta-spiral offers a probable site for interactions with Ca2+ ions. Muatations in the human amelogenin gene (AMGX) cause X-linked hypoplastic amelogenesis imperfecta, a disease characterised by defective enamel. A 9bp deletion in exon 2 of AMGX results in the loss of codons for Ile5, Leu6, Phe7 and Ala8, and replacement by a new threonine codon, disrupting the 16-residue (Met1-Ala16) amelogenin signal peptide.


Pssm-ID: 197891 [Multi-domain]  Cd Length: 165  Bit Score: 42.85  E-value: 4.62e-04
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207137159   137 PGGHAFNPSSFHWTPTPTHAQTPIFPSAPFAKPPCSFQNGFSP--AMSPFIPPTPFLSFTPIQPPAALVYSQP 207
Cdd:smart00818   77 PGQHSMTPTQHHQPNLPQPAQQPFQPQPLQPPQPQQPMQPQPPvhPIPPLPPQPPLPPMFPMQPLPPLLPDLP 149
 
Name Accession Description Interval E-value
PI3Kc_C2_alpha cd05176
Catalytic domain of Class II Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 1045-1397 0e+00

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: 722.54  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1045 RAELEKQTRLVQLLGALAEKVRQASSSTRQVVLLEGLERVQSFFQKNSCRLPISPSLVAKELNIKVCSFFNSNAVPLKIA 1124
Cdd:cd05176      1 REELEKQTRLVQLLGRVAEKVRQASGSARQVALQDGMERVQSFFQKNKCRLPLSPSLVAKELNIKACSFFSSNAVPLKVA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1125 LVNADPLGDEINVMFKVGEDLRQDMLALQMIRIMDRIWLQEGLDLRIVNFKCISTGKDKGMVELVPSSETLRKIQVEYGV 1204
Cdd:cd05176     81 LVNADPLGEEINVMFKVGEDLRQDMLALQMIKIMDKIWLQEGLDLRMVIFKCLSTGKDRGMVELVPSSDTLRKIQVEYGV 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1205 TGSFKDKPLAEWLRKYNPAEDEYEKASENFIYTCAGCCVATYILGICDRHNDNIMLRSTGHMFHIDFGKFLGHAQMIGSF 1284
Cdd:cd05176    161 TGSFKDKPLAEWLRKYNPSEEEYEKASENFIYSCAGCCVATYVLGICDRHNDNIMLRSTGHMFHIDFGKFLGHAQMFGSF 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1285 KRDRAPFVLTSDMAYVINGGERPTSRFQLFVDLCSQAYNLIRKHSNLFLNLLSLMTQSGLPELTGVQDLKYVYDALQPQT 1364
Cdd:cd05176    241 KRDRAPFVLTSDMAYVINGGEKPTIRFQLFVDLCCQAYNLIRKHTNLFLNLLSLMLSSGLPELTGIQDLKYVFDALQPQT 320

                          330       340       350
                   ....*....|....*....|....*....|...
gi 1207137159 1365 TDAEATIFFTRLIESSLGSVATKFNFFIHNLAQ 1397
Cdd:cd05176    321 TDAEATIFFTRLIESSLGSVATKFNFFIHNLAQ 353
PI3Kc_II cd05166
Catalytic domain of Class II Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 1045-1397 0e+00

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


Pssm-ID: 270710 [Multi-domain]  Cd Length: 352  Bit Score: 646.66  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1045 RAELEKQTRLVQLLGALAEKVRQASSSTRQVVLLEGLERVQSFFQKNSCRLPISPSLVAKELNIKVCSFFNSNAVPLKIA 1124
Cdd:cd05166      1 REEFLKQHVLVQALTSIAEKVKSAKDSARENALRRELEQLASFLLENSFRLPLDPALEVTGVDVRSCSYFNSNALPLKLV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1125 LVNADPLGDEINVMFKVGEDLRQDMLALQMIRIMDRIWLQEGLDLRIVNFKCISTGKDKGMVELVPSSETLRKIQVEYGV 1204
Cdd:cd05166     81 FRNADPRAEPISVIFKVGDDLRQDMLTLQLIRIMDKIWLQEGLDLKMITFRCVPTGNKRGMVELVPEAETLREIQTEHGL 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1205 TGSFKDKPLAEWLRKYNPAEDEYEKASENFIYTCAGCCVATYILGICDRHNDNIMLRSTGHMFHIDFGKFLGHAQMIGSF 1284
Cdd:cd05166    161 TGSFKDRPLADWLQKHNPSELEYEKAVENFIRSCAGYCVATYVLGICDRHNDNIMLKTSGHLFHIDFGKFLGDAQMFGNF 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1285 KRDRAPFVLTSDMAYVINGGERPTSRFQLFVDLCSQAYNLIRKHSNLFLNLLSLMTQSGLPELTgVQDLKYVYDALQPQT 1364
Cdd:cd05166    241 KRDRVPFVLTSDMAYVINGGDKPSSRFQLFVDLCCQAFNIIRKNSNLLLNLLSLMLSSGIPGVT-QDDLRYVQDALLPEL 319

                          330       340       350
                   ....*....|....*....|....*....|...
gi 1207137159 1365 TDAEATIFFTRLIESSLGSVATKFNFFIHNLAQ 1397
Cdd:cd05166    320 TDAEATAHFTRMIEESLSSKFTQLNFFIHNLAQ 352
PI3Kc_C2_beta cd00895
Catalytic domain of Class II Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 1045-1397 0e+00

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: 546.14  E-value: 0e+00
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1045 RAELEKQTRLVQLLGALAEKVRQASSSTRQVVLLEGLERVQSFFQKN-SCRLPISPSLVAKELNIKVCSFFNSNAVPLKI 1123
Cdd:cd00895      1 REEFDRQCWLVNVLAKLAQQVREAAPSARQGILREGLEEVKQFFSINgSCRLPLSPSLLVKGIVPRDCSYFNSNAVPLKL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1124 ALVNADPLGDEINVMFKVGEDLRQDMLALQMIRIMDRIWLQEGLDLRIVNFKCISTGKDKGMVELVPSSETLRKIQVEYG 1203
Cdd:cd00895     81 SFQNVDPLGENIRVIFKCGDDLRQDMLTLQMIRIMNKIWVQEGLDMRMVIFRCFSTGRGRGMVEMIPNAETLRKIQVEHG 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1204 VTGSFKDKPLAEWLRKYNPAEDEYEKASENFIYTCAGCCVATYILGICDRHNDNIMLRSTGHMFHIDFGKFLGHAQMIGS 1283
Cdd:cd00895    161 VTGSFKDRPLADWLQKHNPTEDEYEKAVENFIYSCAGCCVATYVLGICDRHNDNIMLKTTGHMFHIDFGRFLGHAQMFGN 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1284 FKRDRAPFVLTSDMAYVINGGERPTSRFQLFVDLCSQAYNLIRKHSNLFLNLLSLMTQSGLPELTGVQDLKYVYDALQPQ 1363
Cdd:cd00895    241 IKRDRAPFVFTSDMAYVINGGDKPSSRFHDFVDLCCQAYNLIRKHTHLFLNLLGLMLSCGIPELSDLEDLKYVYDALRPQ 320

                          330       340       350
                   ....*....|....*....|....*....|....
gi 1207137159 1364 TTDAEATIFFTRLIESSLGSVATKFNFFIHNLAQ 1397
Cdd:cd00895    321 DTEADATTYFTRLIESSLGSVATKLNFFIHNLAQ 354
PI3Kc cd00891
Catalytic domain of Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 1045-1382 1.45e-155

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: 477.83  E-value: 1.45e-155
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1045 RAELEKQTRLVQLLGALAEKVRQASSSTRQVVLLEGLERVQSFfqkNSCRLPISPSLVAKELNIKVCSFFNSNAVPLKIA 1124
Cdd:cd00891      1 REELLKQVKVLDELKEIAKKIKEEPSEERKEVLEKLLQKLELP---KKFTLPLDPRMEVKGLIVEKCKVMDSKKLPLWLV 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1125 LVNADPLGDEINVMFKVGEDLRQDMLALQMIRIMDRIWLQEGLDLRIVNFKCISTGKDKGMVELVPSSETLRKIQVEYG- 1203
Cdd:cd00891     78 FKNADPGGDPIKVIFKAGDDLRQDQLTLQLLRIMDKLWKKEGLDLRMTPYKCIATGDEVGMIEVVPNSETTAAIQKKYGg 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1204 VTGSFKDKPLAEWLRKYNPAEDEYEKASENFIYTCAGCCVATYILGICDRHNDNIMLRSTGHMFHIDFGKFLGHAQMIGS 1283
Cdd:cd00891    158 FGAAFKDTPISNWLKKHNPTEEEYEEAVENFIRSCAGYCVATYVLGIGDRHNDNIMVTKSGHLFHIDFGHFLGNFKKKFG 237

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1284 FKRDRAPFVLTSDMAYVINGGErpTSRFQLFVDLCSQAYNLIRKHSNLFLNLLSLMTQSGLPELTGVQDLKYVYDALQPQ 1363
Cdd:cd00891    238 IKRERAPFVFTPEMAYVMGGED--SENFQKFEDLCCKAYNILRKHGNLLINLFSLMLSAGIPELQSIEDIEYLRDALQLD 315

                          330
                   ....*....|....*....
gi 1207137159 1364 TTDAEATIFFTRLIESSLG 1382
Cdd:cd00891    316 LSDEEAAEHFRKLIHESLN 334
PI3Kc_C2_gamma cd05177
Catalytic domain of Class II Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 1045-1397 1.18e-150

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: 465.52  E-value: 1.18e-150
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1045 RAELEKQTRLVQLLGALAEKVRQASSSTRQVVLLEGLERVQSFFQK-NSCRLPISPSLVAKELNIKVCSFFNSNAVPLKI 1123
Cdd:cd05177      1 NKEFSKETKLISILIDAAEKVKTASDTRRKEVLKREASRLEDFFQDvVSCCLPLNPALRVKGIDADACSYFTSNAAPLKI 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1124 ALVNADPLGDEINVMFKVGEDLRQDMLALQMIRIMDRIWLQEGLDLRIVNFKCISTGKDKGMVELVPSSETLRKIQVEYG 1203
Cdd:cd05177     81 SFINANPLAKNISIIFKTGDDLRQDMLVLQIVRVMDNIWLQEGLDMQMIIYRCLSTGKTQGLVQMVPDAVTLAKIHRESG 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1204 VTGSFKDKPLAEWLRKYNPAEDEYEKASENFIYTCAGCCVATYILGICDRHNDNIMLRSTGHMFHIDFGKFLGHAQMIGS 1283
Cdd:cd05177    161 LIGPLKENTIEKWFHMHNKLKEDYDKAVRNFFHSCAGWCVVTFILGVCDRHNDNIMLTHSGHMFHIDFGKFLGHAQTFGS 240

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1284 FKRDRAPFVLTSDMAYVINGGERPTSRFQLFVDLCSQAYNLIRKHSNLFLNLLSLMTQSGLPELTGVQDLKYVYDALQPQ 1363
Cdd:cd05177    241 IKRDRAPFIFTSEMEYFITEGGKKPQRFQRFVELCCRAYNIVRKHSQLLLNLLEMMLHAGLPELKDIQDLKYVYNNLRPQ 320

                          330       340       350
                   ....*....|....*....|....*....|....
gi 1207137159 1364 TTDAEATIFFTRLIESSLGSVATKFNFFIHNLAQ 1397
Cdd:cd05177    321 DTDLEATSYFTKKIKESLECFPVKLNNLIHTLAQ 354
PI3Kc_I cd05165
Catalytic domain of Class I Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 1047-1397 1.68e-111

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: 358.49  E-value: 1.68e-111
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1047 ELEKQTRLVQLLGALAEKVRQA-SSSTRQVVLLEGLERVQSffqknscrlPISPSLVAKELNIKVCSFFNSNAVPLKIAL 1125
Cdd:cd05165     13 KLKKLSDILKEKKKSKEKVKKLlKECLKQKFYDEALQNFQS---------PLNPSHKLGELIIEKCKVMDSKKRPLWLVF 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1126 VNADPL---GDEINVMFKVGEDLRQDMLALQMIRIMDRIWLQEGLDLRIVNFKCISTGKDKGMVELVPSSETLRKIQVEY 1202
Cdd:cd05165     84 ENADPLalsGEDIKIIFKNGDDLRQDMLTLQIIRIMDNIWKEEGLDLRMLPYGCLSTGDNVGLIEVVRNAKTIANIQKKK 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1203 G--VTGSFKDKPLAEWLRKYNPAEDEYEKASENFIYTCAGCCVATYILGICDRHNDNIMLRSTGHMFHIDFGKFLGHAQM 1280
Cdd:cd05165    164 GkvATLAFNKDSLHKWLKEKNKTGEKYDRAIEEFTLSCAGYCVATYVLGIGDRHSDNIMVKENGQLFHIDFGHFLGNFKK 243

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1281 IGSFKRDRAPFVLTSDMAYVI-NGGERPTS-RFQLFVDLCSQAYNLIRKHSNLFLNLLSLMTQSGLPELTGVQDLKYVYD 1358
Cdd:cd05165    244 KFGIKRERVPFVLTHDFVYVIaRGQDNTKSeEFQEFQELCEKAYLILRRHGNLFISLFSMMLSTGIPELTSVKDIEYLRK 323

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|
gi 1207137159 1359 ALQPQTTDAEATIFFTRLIESSL-GSVATKFNFFIHNLAQ 1397
Cdd:cd05165    324 TLALDKTEEEALKYFRKKFNEALkGSWTTKVNWFFHNVKH 363
PI3Kc_IA_delta cd05174
Catalytic domain of Class IA Phosphoinositide 3-kinase delta; PI3Ks catalyze the transfer of ...
 1048-1397 5.52e-84

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: 280.40  E-value: 5.52e-84
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1048 LEKQTRLVQLLGALAEKVRQASSST-------------RQVVLLEGLERVQSffqknscrlPISPSLVAKELNIKVCSFF 1114
Cdd:cd05174      7 LMKQGEALSKMKALNDFVKVSSQKAtkpqtkemmhvcmKQETYMEALSHLQS---------PLDPSIILEEVCVDQCTFM 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1115 NSNAVPLKIALVNADPLGDEINVMFKVGEDLRQDMLALQMIRIMDRIWLQEGLDLRIVNFKCISTGKDKGMVELVPSSET 1194
Cdd:cd05174     78 DSKMKPLWIMYSSEEAGAGNVGIIFKNGDDLRQDMLTLQMIQLMDVLWKQEGLDLRMTPYGCLSTGDKTGLIEVVLHSDT 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1195 LRKIQV---EYGVTGSFKDKPLAEWLRKYNPAeDEYEKASENFIYTCAGCCVATYILGICDRHNDNIMLRSTGHMFHIDF 1271
Cdd:cd05174    158 IANIQLnksNMAATAAFNKDALLNWLKSKNPG-DALDQAIEEFTLSCAGYCVATYVLGIGDRHSDNIMIRESGQLFHIDF 236

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1272 GKFLGHAQMIGSFKRDRAPFVLTSDMAYVINGGERPTS-RFQLFVDLCSQAYNLIRKHSNLFLNLLSLMTQSGLPELTGV 1350
Cdd:cd05174    237 GHFLGNFKTKFGINRERVPFILTYDFVHVIQQGKTNNSeKFERFRGYCERAYTILRRHGLLFLHLFALMKAAGLPELSCS 316

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*...
gi 1207137159 1351 QDLKYVYDALQPQTTDAEATIFF-TRLIESSLGSVATKFNFFIHNLAQ 1397
Cdd:cd05174    317 KDIQYLKDSLALGKTEEEALKHFrVKFNEALRESWKTKVNWLAHNVSK 364
PI3Kc_IB_gamma cd00894
Catalytic domain of Class IB Phosphoinositide 3-kinase gamma; PI3Ks catalyze the transfer of ...
 1046-1393 1.13e-82

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: 276.74  E-value: 1.13e-82
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1046 AELEKQTRLVQLLGALAEKVRQASSS----TRQVV--LLEGLERVQSFFQKNSCRLPISPSLVAKELNIKVCSFFNSNAV 1119
Cdd:cd00894      2 HDFTQQVQVIEMLQKVTLDIKSLSAEkydvSSQVIsqLKQKLENLQNSQLPESFRVPYDPGLRAGALVIEKCKVMASKKK 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1120 PLKIALVNADPLG---DEINVMFKVGEDLRQDMLALQMIRIMDRIWLQEGLDLRIVNFKCISTGKDKGMVELVPSSETLR 1196
Cdd:cd00894     82 PLWLEFKCADPTAlsnETIGIIFKHGDDLRQDMLILQILRIMESIWETESLDLCLLPYGCISTGDKIGMIEIVKDATTIA 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1197 KIQ-VEYGVTGSFKDKPLAEWLRKYNPAEDEYEKASENFIYTCAGCCVATYILGICDRHNDNIMLRSTGHMFHIDFGKFL 1275
Cdd:cd00894    162 KIQqSTVGNTGAFKDEVLNHWLKEKCPIEEKFQAAVERFVYSCAGYCVATFVLGIGDRHNDNIMITETGNLFHIDFGHIL 241

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1276 GHAQMIGSFKRDRAPFVLTSDMAYVI-NGGERPTSRFQLFVDLCSQAYNLIRKHSNLFLNLLSLMTQSGLPELTGVQDLK 1354
Cdd:cd00894    242 GNYKSFLGINKERVPFVLTPDFLFVMgTSGKKTSLHFQKFQDVCVKAYLALRHHTNLLIILFSMMLMTGMPQLTSKEDIE 321

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|
gi 1207137159 1355 YVYDALQPQTTDAEATIFFTRLIESSLGSVAT-KFNFFIH 1393
Cdd:cd00894    322 YIRDALTVGKSEEDAKKHFLDQIEVCRDKGWTvQFNWFLH 361
PI3Kc_IA_beta cd05173
Catalytic domain of Class IA Phosphoinositide 3-kinase beta; PI3Ks catalyze the transfer of ...
 1073-1397 3.73e-80

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: 269.14  E-value: 3.73e-80
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1073 RQVVLLEGLERVQSffqknscrlPISPSLVAKELNIKVCSFFNSNAVPLKIALVNADPLGDEINVMFKVGEDLRQDMLAL 1152
Cdd:cd05173     42 RQSAYREALSDLQS---------PLNPSIILSELNVEKCKYMDSKMKPLWIVYNNKLFGGDSLGIIFKNGDDLRQDMLTL 112

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1153 QMIRIMDRIWLQEGLDLRIVNFKCISTGKDKGMVELVPSSETLRKIQVE---YGVTGSFKDKPLAEWLRKYNPAeDEYEK 1229
Cdd:cd05173    113 QILRLMDTLWKEAGLDLRIVPYGCLATGDRSGLIEVVSSAETIADIQLNssnVAAAAAFNKDALLNWLKEYNSG-DDLER 191

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1230 ASENFIYTCAGCCVATYILGICDRHNDNIMLRSTGHMFHIDFGKFLGHAQMIGSFKRDRAPFVLTSDMAYVINGGER-PT 1308
Cdd:cd05173    192 AIEEFTLSCAGYCVATYVLGIGDRHSDNIMVRKNGQLFHIDFGHILGNFKSKFGIKRERVPFILTYDFIHVIQQGKTgNT 271

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1309 SRFQLFVDLCSQAYNLIRKHSNLFLNLLSLMTQSGLPELTGVQDLKYVYDALQPQTTDAEATIFFTRLIESSLG-SVATK 1387
Cdd:cd05173    272 EKFGRFRQYCEDAYLILRKNGNLFITLFALMLTAGLPELTSVKDIQYLKDSLALGKSEEEALKQFRQKFDEALReSWTTK 351

                          330
                   ....*....|
gi 1207137159 1388 FNFFIHNLAQ 1397
Cdd:cd05173    352 VNWMAHTVRK 361
PI3Kc_III cd00896
Catalytic domain of Class III Phosphoinositide 3-kinase; PI3Ks catalyze the transfer of the ...
 1045-1397 8.19e-80

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


Pssm-ID: 270628 [Multi-domain]  Cd Length: 346  Bit Score: 267.48  E-value: 8.19e-80
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1045 RAELEKQTRLVQLLGALAEKVRQASSSTRQVV-LLEGL---ERVQSFFQKNSCRLPISPSLVAKELNIKVCSFFNSNAVP 1120
Cdd:cd00896      1 REALKRQQEFVDRLRSLMKEVKNEKGSRDKKIeRLRELlsdSELGLLLFFEPLPLPLDPSVKVTGIIPEKSTVFKSALMP 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1121 LKIALVNADplGDEINVMFKVGEDLRQDMLALQMIRIMDRIWLQEGLDLRIVNFKCISTGKDKGMVELVPSSETLRKIQV 1200
Cdd:cd00896     81 LKLTFKTLD--GGEYKVIFKHGDDLRQDQLVLQIITLMDRLLKKENLDLKLTPYKVLATSPNDGLVEFVPNSKALADILK 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1201 EYGvtgsfkdkPLAEWLRKYNPAED----EYEKASENFIYTCAGCCVATYILGICDRHNDNIMLRSTGHMFHIDFGKFLG 1276
Cdd:cd00896    159 KYG--------SILNFLRKHNPDESgpygIKPEVMDNFVKSCAGYCVITYILGVGDRHLDNLLLTKDGHLFHIDFGYILG 230

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1277 haqmigsfkRDRAPFV----LTSDMayvING-GERPTSRFQLFVDLCSQAYNLIRKHSNLFLNLLSLMTQSGLPELTGVQ 1351
Cdd:cd00896    231 ---------RDPKPFPppmkLCKEM---VEAmGGANSEGYKEFKKYCCTAYNILRKHANLILNLFSLMVDANIPDIALEP 298

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....*...
gi 1207137159 1352 D--LKYVYDALQPQTTDAEATIFFTRLIESSLGSVATKFNFFIHNLAQ 1397
Cdd:cd00896    299 DkaVLKVQEKFRLDLSDEEAEQYFQNLIDESVNALFPAVVETIHKIAQ 346
PX_PI3K_C2_alpha cd07289
The phosphoinositide binding Phox Homology Domain of the Alpha Isoform of Class II ...
 1428-1536 2.81e-74

The phosphoinositide binding Phox Homology Domain of the Alpha Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II alpha isoform, PI3K-C2alpha, plays key roles in clathrin assembly and clathrin-mediated membrane trafficking, insulin signaling, vascular smooth muscle contraction, and the priming of neurosecretory granule exocytosis. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


Pssm-ID: 132822  Cd Length: 109  Bit Score: 241.76  E-value: 2.81e-74
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1428 DASVFSFQKRYNPDKHYTYVIRILREGQSEPQFVFRTFDEFQELHNKLTILFQLWKLPGFPSKMVLGRTHIKDVASKRKV 1507
Cdd:cd07289      1 EVSVFTYHKRYNPDKHYIYVVRILREGQIEPSFVFRTFDEFQELHNKLSILFPLWKLPGFPNKMVLGRTHIKDVAAKRKV 80

                           90       100
                   ....*....|....*....|....*....
gi 1207137159 1508 ELNSYVHNLMRSSTEVAQCDLIYTFFHPI 1536
Cdd:cd07289     81 ELNSYIQSLMNSSTEVAECDLVYTFFHPL 109
C2A_PI3K_class_II cd04012
C2 domain first repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 ...
 681-852 1.14e-71

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: 236.87  E-value: 1.14e-71
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  681 KEASGTTEHLQFTLFAVHGIPATWVSSFEKYYLMCALTHNNRNLFKPVQSKKVGTYKSFFYHIKWDELINFPISVSLLPL 760
Cdd:cd04012      1 REASTVTDLLSVTVSSLHRIPPTWVQSFEDFYLSCSLYHGGRLLCSPVTTKPVKITKSFFPRVVWDEWIEFPIPVCQLPR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  761 EAMLSLSLYGVLSQNANNspdSNKQRKGPELLGKVSMPLFDFRRVLSRGSKLLSLWTSPQALQPGAAGKGRNPTEK-IIL 839
Cdd:cd04012     81 ESRLVLTLYGTTSSPDGG---SNKQRMGPEELGWVSLPLFDFRGVLRQGSLLLGLWPPSKDNPLGPAPPPLFEQPDrVIL 157

                          170
                   ....*....|...
gi 1207137159  840 QVDFPSPAVDVLY 852
Cdd:cd04012    158 QIDFPSSAFDVIF 170
PI3Kc smart00146
Phosphoinositide 3-kinase, catalytic domain; Phosphoinositide 3-kinase isoforms participate in ...
 1137-1351 1.60e-70

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: 236.43  E-value: 1.60e-70
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  1137 VMFKVGEDLRQDMLALQMIRIMDRIWLQE----GLDLRIVNFKCISTGKDKGMVELVPSSETLRKIQVEY---------- 1202
Cdd:smart00146    1 VIFKGGDDLRQDERVLQLLRLMNKLLQKDketrRRDLHLRPYKVIPTGPKSGLIEVVPNSTTLHEILKEYrkqkgkvldl 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  1203 ---------------GVTGSFKDKPLAEWLRKYNPAEDE-YEKASENFIYTCAGCCVATYILGICDRHNDNIMLRSTGHM 1266
Cdd:smart00146   81 rsqtatrlkklelflEATGKFPDPVLYDWFTKKFPDPSEdYFEARKNFTRSCAGYSVITYILGLGDRHNDNIMLDKTGHL 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  1267 FHIDFGKFLGHAQMIGSFKrDRAPFVLTSDMAYVINggerPTSRFQLFVDLCSQAYNLIRKHSNLFLNLLSLMTQSGLPE 1346
Cdd:smart00146  161 FHIDFGFILGNGPKLFGFP-ERVPFRLTPEMVDVMG----DSGYFGLFRSLCERALRALRKNSNLIMSLLELMLYDGLPD 235


                    ....*
gi 1207137159  1347 LTGVQ 1351
Cdd:smart00146  236 WRSGK 240
C2B_PI3K_class_II cd08381
C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are ...
 1565-1686 1.67e-70

C2 domain second repeat present in class II phosphatidylinositol 3-kinases (PI3Ks); There are 3 classes of PI3Ks based on structure, regulation, and specificity. All classes contain a N-terminal C2 domain, a PIK domain, and a kinase catalytic domain. Unlike class I and class III, class II PI3Ks have additionally a PX domain and a C-terminal C2 domain containing a nuclear localization signal both of which bind phospholipids though in a slightly different fashion. PI3Ks (AKA phosphatidylinositol (PtdIns) 3-kinases) regulate cell processes such as cell growth, differentiation, proliferation, and motility. PI3Ks work on phosphorylation of phosphatidylinositol, phosphatidylinositide (4)P (PtdIns (4)P),2 or PtdIns(4,5)P2. Specifically they phosphorylate the D3 hydroxyl group of phosphoinositol lipids on the inositol ring. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176027 [Multi-domain]  Cd Length: 122  Bit Score: 231.80  E-value: 1.67e-70
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1565 EGEVKLSVSYRNSTLFIMVMHIKDLMSNDGADPNPYVKTYLLPDPHKTSKRKTKIARKTRNPTFNEMLVYSGYSKETLKQ 1644
Cdd:cd08381      1 GGQVKLSISYKNGTLFVMVMHAKNLPLLDGSDPDPYVKTYLLPDPQKTTKRKTKVVRKTRNPTFNEMLVYDGLPVEDLQQ 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|..
gi 1207137159 1645 RELQLSVLSAESLRENCYLGGITLCLKDFDLSRETVKWYKLT 1686
Cdd:cd08381     81 RVLQVSVWSHDSLVENEFLGGVCIPLKKLDLSQETEKWYPLG 122
PI3Kc_IA_alpha cd05175
Catalytic domain of Class IA Phosphoinositide 3-kinase alpha; PI3Ks catalyze the transfer of ...
 1044-1397 1.37e-65

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: 227.63  E-value: 1.37e-65
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1044 LRAELEKQTRLVQLLGALAEKVRQASSSTRQVVLLEGLERVQSFFQKNSCRLPISPSLVAKELNIKVCSFFNSNAVPLKI 1123
Cdd:cd05175      8 LSRQVEAMEKLINLTDILKQEKKDETQKVQMKFLVEQMRRPDFMDALQGFLSPLNPAHQLGNLRLEECRIMSSAKRPLWL 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1124 ALVNADPLGDEI----NVMFKVGEDLRQDMLALQMIRIMDRIWLQEGLDLRIVNFKCISTGKDKGMVELVPSSETLRKIQ 1199
Cdd:cd05175     88 NWENPDIMSELLfqnnEIIFKNGDDLRQDMLTLQIIRIMENIWQNQGLDLRMLPYGCLSIGDCVGLIEVVRNSHTIMQIQ 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1200 VEYGVTGS--FKDKPLAEWLRKYNPAEDeYEKASENFIYTCAGCCVATYILGICDRHNDNIMLRSTGHMFHIDFGKFLGH 1277
Cdd:cd05175    168 CKGGLKGAlqFNSHTLHQWLKDKNKGEI-YDAAIDLFTRSCAGYCVATFILGIGDRHNSNIMVKDDGQLFHIDFGHFLDH 246

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1278 AQMIGSFKRDRAPFVLTSDMAYVINGGER---PTSRFQLFVDLCSQAYNLIRKHSNLFLNLLSLMTQSGLPELTGVQDLK 1354
Cdd:cd05175    247 KKKKFGYKRERVPFVLTQDFLIVISKGAQectKTREFERFQEMCYKAYLAIRQHANLFINLFSMMLGSGMPELQSFDDIA 326

                          330       340       350       360
                   ....*....|....*....|....*....|....*....|....
gi 1207137159 1355 YVYDALQPQTTDAEATIFFTRLI-ESSLGSVATKFNFFIHNLAQ 1397
Cdd:cd05175    327 YIRKTLALDKTEQEALEYFMKQMnDAHHGGWTTKMDWIFHTIKQ 370
PI3Ka_II cd00869
Phosphoinositide 3-kinase (PI3K) class II, accessory domain (PIK domain); PIK domain is ...
 872-1038 3.70e-65

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: 218.48  E-value: 3.70e-65
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  872 DDRSEIEKLCARASTFGLSRADRQLLWDQRYYCREYEYSLPKILASAPSWDWGSMGEIHALLHHWPALSPVSALELLESK 951
Cdd:cd00869      2 ETQEKLLDLIQKQSTYTLSTEDKDLLWEKRLYCTNEPNALPLVLASAPSWDWANLMDVYQLLHQWAPLRPLIALELLLPK 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  952 FADTEVRKVAVSWIQSSSDDELADYLPQLVQAVKFECHLNNALVKFLLSRALGNVNIAHYLYWLLRDAVQDPAFGQRYER 1031
Cdd:cd00869     82 FPDQEVRAHAVQWLARLSNDELLDYLPQLVQALKFELYLKSALVRFLLSRSLVSLRFAHELYWLLKDALDDCYFSSAYQD 161


                   ....*..
gi 1207137159 1032 ILCVLLC 1038
Cdd:cd00869    162 LGAALRC 168
PI3_PI4_kinase pfam00454
Phosphatidylinositol 3- and 4-kinase; Some members of this family probably do not have lipid ...
 1134-1348 6.62e-65

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: 220.66  E-value: 6.62e-65
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1134 EINVMFKVGEDLRQDMLALQMIRIMDRIWLQEGLDL-RIVNFKCISTGKDKGMVELVPSSETLRKIQVEYG-----VTGS 1207
Cdd:pfam00454    1 GYGGIYKVGDDLRQDELILQVFKLMDEELSKDNLDLrRLKPYSVIPLGPKCGIIEWVPNSETLAYILDEYGengvpPTAM 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1208 FKDK-----------------------PLAEWLRKYNPAEDEYEKASENFIYTCAGCCVATYILGICDRHNDNIML-RST 1263
Cdd:pfam00454   81 VKILhsalnypklklefesrislppkvGLLQWFVKKSPDAEEWGEARKNFVRSCAGYSVLDYILGNGDRHLDNILVdKTT 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1264 GHMFHIDFGKFLGHAQMIGSFKrDRAPFVLTSDMAYVINggerPTSRFQLFVDLCSQAYNLIRKHSNLFLNLLSLMTQSG 1343
Cdd:pfam00454  161 GKLFHIDFGLCLPDAGKDLPFP-EKVPFRLTREMVYAMG----PSGDEGLFRELCETAYEALRRNLNLLTNLLKLMVADG 235


                   ....*
gi 1207137159 1344 LPELT 1348
Cdd:pfam00454  236 LPDWS 240
PI3Ka smart00145
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 868-1049 1.77e-55

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: 191.32  E-value: 1.77e-55
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159   868 PLDQDDRSEIEKLCARASTFGLSRADRQLLWDQRYYC-REYEYSLPKILaSAPSWDWGS-MGEIHALLHHWPALSPVSAL 945
Cdd:smart00145    2 PLDIEEREQLEAILKLDPTYELTEEEKDLIWKFRHYYlTNNPKALPKFL-LSVKWSDADeVAQALSLLLSWAPLDPEDAL 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159   946 ELLESKFADTEVRKVAVSWIQSSSDDELADYLPQLVQAVKFECHLNNALVKFLLSRALGNVNIAHYLYWLLRDAVQDPAF 1025
Cdd:smart00145   81 ELLDPKFPDPFVRAYAVKRLESASDEELLLYLLQLVQALKYEPYLDSALARFLLERALANQRLGHFFYWYLKSELHDPHV 160

                           170       180
                    ....*....|....*....|....
gi 1207137159  1026 GQRYERILCVLLCLCGTGLRAELE 1049
Cdd:smart00145  161 SIRFGLLLEAYLRGCGTHLKELLK 184
PI4Kc_III cd00893
Catalytic domain of Type III Phosphoinositide 4-kinase; PI4Ks catalyze the transfer of the ...
 1137-1387 1.13e-53

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: 189.78  E-value: 1.13e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1137 VMFKVGEDLRQDMLALQMIRIMDRIWLQEGLDLRIVNFKCISTGKDKGMVELVPSSETLRKIQVEYGVTGSFKDkpLAEW 1216
Cdd:cd00893     30 LIVKTGDDLKQEQLALQLISQFDQIFKEEGLPLWLRPYEILSLGPDSGIIEMIKNAVSIDSLKKKLDSFNKFVS--LSDF 107

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1217 LRKYNPAEdEYEKASENFIYTCAGCCVATYILGICDRHNDNIMLRSTGHMFHIDFGKFLGHAQmiGSFKRDRAPFVLTSD 1296
Cdd:cd00893    108 FDDNFGDE-AIQKARDNFLQSLVAYSLVCYFLQIKDRHNGNILLDKEGHIIHIDFGFFLSSHP--GFYGFEGAPFKLSSE 184

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1297 MAYVIngGERPTSRFQLFVDLCSQAYNLIRKHSNLFLNLLSLMTQSGLPELTGVQDLKYVYDALQPQTTDAEATIFFTRL 1376
Cdd:cd00893    185 YIEVL--GGVDSELFKEFRKLFLKGFMALRKHSDKILSLVEMMYSGHGITCFGKKTIQQLKQRFNPELTEGELEVYVLSL 262

                          250
                   ....*....|.
gi 1207137159 1377 IESSLGSVATK 1387
Cdd:cd00893    263 INKSLDNWRTR 273
PX_PI3K_C2 cd06883
The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases; The ...
 1428-1536 1.93e-53

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. They are also involved in the regulation of clathrin-mediated membrane trafficking as well as ATP-dependent priming of neurosecretory granule exocytosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. Class II PI3Ks include three vertebrate isoforms (alpha, beta, and gamma), the Drosophila PI3K_68D, and similar proteins.


Pssm-ID: 132793  Cd Length: 109  Bit Score: 182.17  E-value: 1.93e-53
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1428 DASVFSFQKRYNPDKHYTYVIRILREGQSEPQFVFRTFDEFQELHNKLTILFQLWKLPGFPSKMVLGRTHIKDVASKRKV 1507
Cdd:cd06883      1 EVSVFGFQKRYSPEKYYIYVVKVTRENQTEPSFVFRTFEEFQELHNKLSLLFPSLKLPSFPARVVLGRSHIKQVAERRKI 80

                           90       100
                   ....*....|....*....|....*....
gi 1207137159 1508 ELNSYVHNLMRSSTEVAQCDLIYTFFHPI 1536
Cdd:cd06883     81 ELNSYLKSLFNASPEVAESDLVYTFFHPL 109
PI4Kc_III_alpha cd05167
Catalytic domain of Type III Phosphoinositide 4-kinase alpha; PI4Ks catalyze the transfer of ...
 1134-1388 1.04e-51

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: 185.10  E-value: 1.04e-51
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1134 EINVMFKVGEDLRQDMLALQMIRIMDRIWLQEGLDLRIVNFKCISTGKDKGMVELVPSSETLRKIqveygvtGSFKDKPL 1213
Cdd:cd05167     49 WQAAIFKVGDDCRQDMLALQLISLFKNIFEEVGLDLYLFPYRVVATGPGCGVIEVIPNSKSRDQI-------GRETDNGL 121

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1214 AEW-LRKYNPAED-EYEKASENFIYTCAGCCVATYILGICDRHNDNIMLRSTGHMFHIDFGkFLGHAQMIGSFKRDRAPF 1291
Cdd:cd05167    122 YEYfLSKYGDESTpAFQKARRNFIKSMAGYSLVSYLLQIKDRHNGNIMIDDDGHIIHIDFG-FIFEISPGGNLGFESAPF 200

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1292 VLTSDMAYVInGGERPTSRFQLFVDLCSQAYNLIRKHSNLFLNLLSLMTQSGLPELTGvQDLKYVYDALQPQTTDAEATI 1371
Cdd:cd05167    201 KLTKEMVDLM-GGSMESEPFKWFVELCVRGYLAVRPYAEAIVSLVELMLDSGLPCFRG-QTIKNLRERFALEMSEREAAN 278

                          250
                   ....*....|....*..
gi 1207137159 1372 FFTRLIESSLGSVATKF 1388
Cdd:cd05167    279 FMIKLIADSYLKIRTKG 295
PI4Kc_III_beta cd05168
Catalytic domain of Type III Phosphoinositide 4-kinase beta; PI4Ks catalyze the transfer of ...
 1137-1387 4.66e-49

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: 176.90  E-value: 4.66e-49
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1137 VMFKVGEDLRQDMLALQMIRIMDRIWLQEGLDLRIVNFKCISTGKDKGMVELVPSSETLRKIQVEYGVTGSFKDkplaEW 1216
Cdd:cd05168     33 VIVKSGDDLRQELLAMQLIKQFQRIFEEAGLPLWLRPYEILVTSSDSGLIETIPDTVSIDSLKKRFPNFTSLLD----YF 108

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1217 LRKY-NPAEDEYEKASENFIYTCAGCCVATYILGICDRHNDNIMLRSTGHMFHIDFGKFLGHAQmiGSFKRDRAPFVLTS 1295
Cdd:cd05168    109 ERTFgDPNSERFKEAQRNFVESLAAYSLVCYLLQIKDRHNGNILLDSEGHIIHIDFGFMLSNSP--GGLGFETAPFKLTQ 186

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1296 DMAYVINGGERPtsRFQLFVDLCSQAYNLIRKHSNLFLNLLSLMTQS-------GLPELTgVQDLKyvyDALQPQTTDAE 1368
Cdd:cd05168    187 EYVEVMGGLESD--MFRYFKTLMIQGFLALRKHADRIVLLVEIMQQGsklpcffGGGEFT-IEQLR---ERFKLNLTEEE 260

                          250
                   ....*....|....*....
gi 1207137159 1369 ATIFFTRLIESSLGSVATK 1387
Cdd:cd05168    261 CAQFVDSLIDKSLNNWRTR 279
PI3Ka cd00864
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 872-1022 7.40e-49

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: 170.86  E-value: 7.40e-49
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  872 DDRSEIEKLCARASTFGLSRADRQLLWDQRYYCREYEYSLPKILASAPSWDWGSMGEIHALLHHWPALSPVSALELLESK 951
Cdd:cd00864      2 WERKPLLAILLYPPFSTLTEEEKELLWKFRYYLLNVPKALPKLLKSVNWNDDEEVSELYQLLKWWAPLSPEDALELLSPK 81

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1207137159  952 FADTEVRKVAVSWIQSSSDDELADYLPQLVQAVKFECHLNNALVKFLLSRALGNVNIAHYLYWLLRDAVQD 1022
Cdd:cd00864     82 YPDPVVRQYAVRVLESASDDELLLYLPQLVQALKYEPYLDSYLARFLLERALKSQRLGHQLYWNLKSEIHD 152
PI3Ka_I cd00872
Phosphoinositide 3-kinase (PI3K) class I, accessory domain ; PIK domain is conserved in all ...
 872-1041 3.06e-44

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: 158.63  E-value: 3.06e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  872 DDRSEIEKLCARASTFGLSRADRQLLWDQRYYCREYEYSLPKILASAPswdWGS---MGEIHALLHHWPALSPVSALELL 948
Cdd:cd00872      2 EEREQLEAIIARDPLSELTEEDKELLWKLRHECRKKPQALPKLLLSVK---WNKrddVAQMYQLLKRWPKLKPEQALELL 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  949 ESKFADTEVRKVAVSWIQSSSDDELADYLPQLVQAVKFECHLNNALVKFLLSRALGNVNIAHYLYWLLRDAVQDPAFGQR 1028
Cdd:cd00872     79 DCNFPDEHVREFAVRCLEKLSDDELLQYLLQLVQVLKYEPYHDSDLVRFLLKRALRNQRIGHFFFWHLRSEMHNPSVSQR 158

                          170
                   ....*....|...
gi 1207137159 1029 YERILCVLLCLCG 1041
Cdd:cd00872    159 FGLLLEAYLRGCG 171
PI3Ka pfam00613
Phosphoinositide 3-kinase family, accessory domain (PIK domain); PIK domain is conserved in ...
 868-1045 6.22e-40

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: 146.71  E-value: 6.22e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  868 PLDQDDRSEIEKLCARASTFGLSRADRQLLWDQRYYCREYEYSLPKILASAPswdWGSMGEIHALLHH---WPALSPVSA 944
Cdd:pfam00613    4 KPNEKERKELEAILAYDPLSKLTAEEKDLIWKFRYYLMLVPKALTKLLLSVK---WSDLSEVAEALSLllkWAPIDPVDA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  945 LELLESKFADTEVRKVAVSWIQSSSDDELADYLPQLVQAVKFECHLNNALVKFLLSRALGNVNIAHYLYWLLRDAVQDPA 1024
Cdd:pfam00613   81 LELLDPKFPDPEVRQYAVKCLESASDDELLFYLLQLVQALKYEPFHDSYLSRFLLQRALKNRRIGHFFFWYLKSEIHDEE 160

                          170       180
                   ....*....|....*....|.
gi 1207137159 1025 FGQRYERILCVLLCLCGTGLR 1045
Cdd:pfam00613  161 VSPRFGSLLELYLRSCGTSLL 181
PX_PI3K_C2_beta cd07290
The phosphoinositide binding Phox Homology Domain of the Beta Isoform of Class II ...
 1435-1536 1.55e-37

The phosphoinositide binding Phox Homology Domain of the Beta Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II beta isoform, PI3K-C2beta, contributes to the migration and survival of cancer cells. It regulates Rac activity and impacts membrane ruffling, cell motility, and cadherin-mediated cell-cell adhesion. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


Pssm-ID: 132823  Cd Length: 109  Bit Score: 136.98  E-value: 1.55e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1435 QKRYNPDKHYTYVIRILREGQSEPQFVFRTFDEFQELHNKLTILFQLWKLPGFPSKMVLGRTHIKDVASKRKVELNSYVH 1514
Cdd:cd07290      8 ESTFNPSKGYAYVVKVQREGHKEATFVQRTFEEFQELHNKLRLLFPSSKLPSFPSRFVIGRSRGEAVAERRKEELNGYIW 87

                           90       100
                   ....*....|....*....|..
gi 1207137159 1515 NLMRSSTEVAQCDLIYTFFHPI 1536
Cdd:cd07290     88 HLIHAPPEVAECDLVYTFFHPL 109
PI3Kc_like cd00142
Catalytic domain of Phosphoinositide 3-kinase and similar proteins; Members of the family ...
 1105-1328 5.70e-37

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: 139.39  E-value: 5.70e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1105 ELNIKVCSFFNSNAVPLKIALVNADplGDEINVMFKVGEDLRQDMLALQMIRIMDRIWLQEGLDLRIVNFKCISTGKDKG 1184
Cdd:cd00142      2 ALDVGILKVIHSKQRPKKITLIGAD--GKTYSFLLKRRDDLRKDERSFQFMRLIQSILEKESVNLVLPPYKVIPLSENSG 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1185 MVELVPSSETLRKiqveygvtgsfkdkpLAEWLRKYNPAEDEYEKASENFIYTCAGCCVATYILGICDRHNDNIMLRSTG 1264
Cdd:cd00142     80 LIEIVKDAQTIED---------------LLKSLWRKSPSSQSWLNRRENFSCSLAGYSVLGYIFGIGDRHPSNIMIEPSG 144

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207137159 1265 HMFHIDFGKFLGHAQMigSFKRDRAPFVLTSDMAYVINGGerptSRFQLFVDLCSQAYNLIRKH 1328
Cdd:cd00142    145 NIFHIDFGFIFSGRKL--AEGVETVPFRLTPMLENAMGTA----GVNGPFQISMVKIMEILREH 202
PX_PI3K_C2_68D cd06884
The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases ...
 1431-1536 1.49e-36

The phosphoinositide binding Phox Homology Domain of Class II Phosphoinositide 3-Kinases similar to the Drosophila PI3K_68D protein; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. PI3K_68D is a novel PI3K which is widely expressed throughout the Drosophila life cycle. In vitro, it has been shown to phosphorylate PI and PI4P. It is involved in signaling pathways that affect pattern formation of Drosophila wings.


Pssm-ID: 132794  Cd Length: 111  Bit Score: 134.08  E-value: 1.49e-36
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1431 VFSFQKRYNPDKHYTYVIRILREGQSEPQFVFRTFDEFQELHNKLTILFQLWKLPGFPSKMVLGRTHIKDVASKRKVELN 1510
Cdd:cd06884      6 VVGFQKRYDPEKYYVYVVEVTRENQASPQHVFRTYKEFLELYQKLCRKFPLAKLHPLSTGSHVGRSNIKSVAEKRKQDIQ 85

                           90       100
                   ....*....|....*....|....*.
gi 1207137159 1511 SYVHNLMRSSTEVAQCDLIYTFFHPI 1536
Cdd:cd06884     86 QFLNSLFKMAEEVSHSDLVYTFFHPL 111
TEL1 COG5032
Phosphatidylinositol kinase or protein kinase, PI-3 family [Signal transduction mechanisms];
1137-1384 2.61e-29

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


Pssm-ID: 227365 [Multi-domain]  Cd Length: 2105  Bit Score: 128.36  E-value: 2.61e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1137 VMFKVGEDLRQDMLALQMIRIMDRIWLQEGL----DLRIVNFKCISTGKDKGMVELVPSSETLRKIQVEY---------- 1202
Cdd:COG5032   1799 FIVKGGDDLRQDELALQLIRLMNKILKKDKEtrrrDLWIRPYKVIPLSPGSGIIEWVPNSDTLHSILREYhkrknisidq 1878

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1203 --------------------GVTGSFKDKPLAEWLRKYNPAEDEYEKASENFIYTCAGCCVATYILGICDRHNDNIML-R 1261
Cdd:COG5032   1879 ekklaarldnlklllkdeffTKATLKSPPVLYDWFSESFPNPEDWLTARTNFARSLAVYSVIGYILGLGDRHPGNILIdR 1958

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1262 STGHMFHIDFGKFLGHAqmIGSFK-RDRAPFVLTSDMAYVI--NGGErptsrfQLFVDLCSQAYNLIRKHSNLFLNLLSL 1338
Cdd:COG5032   1959 SSGHVIHIDFGFILFNA--PGRFPfPEKVPFRLTRNIVEAMgvSGVE------GSFRELCETAFRALRKNADSLMNVLEL 2030

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|....
gi 1207137159 1339 M------TQSGLPELTGVQ--DLKYVYDALQPQTTDAEATIFFTRLIESSLGSV 1384
Cdd:COG5032   2031 FvrdpliEWRRLPCFREIQnnEIVNVLERFRLKLSEKDAEKFVDLLINKSVESL 2084
PI3K_rbd pfam00794
PI3-kinase family, ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 420-507 1.14e-26

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: 105.84  E-value: 1.14e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  420 GGSVKVSIEISDSQQPVTFTCDVTSPVDLLIMQALCWVHDDLNQVDI-NSYVLKVCGQEEVLQNKHSLGSHEYVQNCRKW 498
Cdd:pfam00794   14 NNKLLISVHLEGDQMTKTFTCNPNSTPGSLIAQALTKKLSVHTQGDVtDDYVLKVCGRDEYLLGDHPLGQFEYIRNCLKS 93


                   ....*....
gi 1207137159  499 ESEIKLQLL 507
Cdd:pfam00794   94 GREPHLTLV 102
C2A_SLP cd08521
C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share ...
 1566-1685 2.74e-26

C2 domain first repeat present in Synaptotagmin-like proteins; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176056 [Multi-domain]  Cd Length: 123  Bit Score: 105.41  E-value: 2.74e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1566 GEVKLSVSYRNST--LFIMVMHIKDLMSNDGAD--PNPYVKTYLLPDPHKTSKRKTKIARKTRNPTFNEMLVYSgYSKET 1641
Cdd:cd08521      1 GEIEFSLSYNYKTgsLEVHIKECRNLAYADEKKkrSNPYVKVYLLPDKSKQSKRKTSVKKNTTNPVFNETLKYH-ISKSQ 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1207137159 1642 LKQRELQLSVLSAESLRENCYLGGITLCLKDFDLSRETVKWYKL 1685
Cdd:cd08521     80 LETRTLQLSVWHHDRFGRNTFLGEVEIPLDSWDLDSQQSEWYPL 123
C2A_SLP-1_2 cd08393
C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members ...
 1566-1685 1.58e-25

C2 domain first repeat present in Synaptotagmin-like proteins 1 and 2; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike Slp3 and Slp4/granuphilin which are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176039 [Multi-domain]  Cd Length: 125  Bit Score: 103.28  E-value: 1.58e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1566 GEVKLSVSY--RNSTLFIMVMHIKDLMSndgADP-----NPYVKTYLLPDPHKTSKRKTKIARKTRNPTFNEMLVYSgYS 1638
Cdd:cd08393      2 GSVQFALDYdpKLRELHVHVIQCQDLAA---ADPkkqrsDPYVKTYLLPDKSNRGKRKTSVKKKTLNPVFNETLRYK-VE 77

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1207137159 1639 KETLKQRELQLSVLSAESLRENCYLGGITLCLKDFDLSRETVKWYKL 1685
Cdd:cd08393     78 REELPTRVLNLSVWHRDSLGRNSFLGEVEVDLGSWDWSNTQPTWYPL 124
C2C_KIAA1228 cd04030
C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins ...
 1566-1686 7.57e-25

C2 domain third repeat present in uncharacterized human KIAA1228-like proteins; KIAA proteins are uncharacterized human proteins. They were compiled by the Kazusa mammalian cDNA project which identified more than 2000 human genes. They are identified by 4 digit codes that precede the KIAA designation. Many KIAA genes are still functionally uncharacterized including KIAA1228. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175996 [Multi-domain]  Cd Length: 127  Bit Score: 101.20  E-value: 7.57e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1566 GEVKLSVSY--RNSTLFIMVMHIKDLMSNDGAD-PNPYVKTYLLPDPHKTSKRKTKIARKTRNPTFNEMLVYSgYSKETL 1642
Cdd:cd04030      3 GRIQLTIRYssQRQKLIVTVHKCRNLPPCDSSDiPDPYVRLYLLPDKSKSTRRKTSVKKDNLNPVFDETFEFP-VSLEEL 81

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*.
gi 1207137159 1643 KQRELQLSVLSAESL--RENCYLGGITLCLKDFDLSRETVKWYKLT 1686
Cdd:cd04030     82 KRRTLDVAVKNSKSFlsREKKLLGQVLIDLSDLDLSKGFTQWYDLT 127
PI3K_rbd smart00144
PI3-kinase family, Ras-binding domain; Certain members of the PI3K family possess Ras-binding ...
 420-507 5.21e-24

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: 98.17  E-value: 5.21e-24
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159   420 GGSVKVSIEISDSQQPVTFTCDVTSPVDLLIMQALCWVHDDLNQVDINS--YVLKVCGQEEVLQNKHSLGSHEYVQNCRK 497
Cdd:smart00144   15 ANKILIVVHLEKDQQTKTLKVNPNCTPDSVLAQAFTKMLSLHDQVDPTSedYILKVCGRDEYLLGDHPLGSFEYIRNCLK 94

                            90
                    ....*....|
gi 1207137159   498 WESEIKLQLL 507
Cdd:smart00144   95 NGTEPHLVLM 104
PI3Ka_III cd00870
Phosphoinositide 3-kinase (PI3K) class III, accessory domain (PIK domain); PIK domain is ...
 872-1022 1.21e-23

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: 99.33  E-value: 1.21e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  872 DDRSEIEKLCARASTFGLSRADRQLLWDQRYYCREYEYSLPKILASApswDWGSMGEIH---ALLHHWPALSPVSALELL 948
Cdd:cd00870      9 KERKELNKILKYPPTTKLTDEEKDLIWKFRFYLTNNKKALTKFLKSV---NWSDEQEVKqalELMPKWAKIDIEDALELL 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  949 ESKFADTEVRKVAVSWIQSSSDDELADYLPQLVQAVKFE-------CHLNNALVKFLLSRALGNVNIAHYLYWLLRDAVQ 1021
Cdd:cd00870     86 SPYFTNPVVRKYAVSRLKLASDEELLLYLLQLVQALKYEnldlsplPRLDSPLADFLIERALKNPKLANFLYWYLKVELE 165


                   .
gi 1207137159 1022 D 1022
Cdd:cd00870    166 D 166
C2A_RIM1alpha cd04031
C2 domain first repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 1564-1685 5.19e-23

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


Pssm-ID: 175997 [Multi-domain]  Cd Length: 125  Bit Score: 95.78  E-value: 5.19e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1564 VEGEVKLSVSYRNST--LFIMVMHIKDL-MSNDGADPNPYVKTYLLPDPHKTSKRKTKIARKTRNPTFNEMLVYSGYSKE 1640
Cdd:cd04031      1 ITGRIQIQLWYDKVTsqLIVTVLQARDLpPRDDGSLRNPYVKVYLLPDRSEKSKRRTKTVKKTLNPEWNQTFEYSNVRRE 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1207137159 1641 TLKQRELQLSVLSAESLRENCYLGGITLCLKDFDLSRETVkWYKL 1685
Cdd:cd04031     81 TLKERTLEVTVWDYDRDGENDFLGEVVIDLADALLDDEPH-WYPL 124
C2A_SLP-4_5 cd04029
C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members ...
 1566-1685 7.82e-23

C2 domain first repeat present in Synaptotagmin-like proteins 4 and 5; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp4/granuphilin promotes dense-core vesicle exocytosis. The C2A domain of Slp4 is Ca2+ dependent. Slp5 mRNA has been shown to be restricted to human placenta and liver suggesting a role in Rab27A-dependent membrane trafficking in specific tissues. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 175995 [Multi-domain]  Cd Length: 125  Bit Score: 95.58  E-value: 7.82e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1566 GEVKLSVSYRNST--LFIMVMHIKDLMSNDGAD--PNPYVKTYLLPDPHKTSKRKTKIARKTRNPTFNEMLVYSgYSKET 1641
Cdd:cd04029      2 GEILFSLSYDYKTqsLNVHVKECRNLAYGDEAKkrSNPYVKTYLLPDKSRQSKRKTSIKRNTTNPVYNETLKYS-ISHSQ 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1207137159 1642 LKQRELQLSVLSAESLRENCYLGGITLCLKDFDLSRETVKWYKL 1685
Cdd:cd04029     81 LETRTLQLSVWHYDRFGRNTFLGEVEIPLDSWNFDSQHEECLPL 124
PI3K_C2 pfam00792
Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 ...
 709-843 1.67e-22

Phosphoinositide 3-kinase C2; Phosphoinositide 3-kinase region postulated to contain a C2 domain. Outlier of pfam00168 family.


Pssm-ID: 395640  Cd Length: 136  Bit Score: 94.74  E-value: 1.67e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  709 EKYYLMCALTHNNRNLFKPVQSKkvgtYKSF-FYHIKWDELINFPISVSLLPLEAMLSLSLYGVLSQNANNSPdsnkqrk 787
Cdd:pfam00792    3 EDLYVECQLYHGGKPLCLPVSTR----YVPFsNSSIKWNEWITFPIQISDLPRSARLCITIWDVSGPEKSFVP------- 71

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*..
gi 1207137159  788 gpelLGKVSMPLFDFRRVLSRGSKLLSLWTSPQalQPGAAGKGR-NPTEKIILQVDF 843
Cdd:pfam00792   72 ----IGWVNTSLFDKKGILRQGKQKLRLWPSKS--TPGRSNVDEmNRLEKLLKKYER 122
PI3K_C2 smart00142
Phosphoinositide 3-kinase, region postulated to contain C2 domain; Outlier of C2 family.
 678-771 3.27e-22

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


Pssm-ID: 214536  Cd Length: 100  Bit Score: 92.79  E-value: 3.27e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159   678 RDSKEASGTTEHLQFTLFAVHGIPATWVSSFEKYYLMCALTHNNRNLFKPVQSkkvgTYKSFFYHIKWDELINFPISVSL 757
Cdd:smart00142    1 VKIESLWDCDRNLVITIALIHGIPLNWSRDYSDLYVEIQLYHGGKLLCLPVST----SYKPFFPSVKWNEWLTFPIQISD 76

                            90
                    ....*....|....
gi 1207137159   758 LPLEAMLSLSLYGV 771
Cdd:smart00142   77 LPREARLCITIYAV 90
C2_PI3K_like cd08380
C2 domain present in phosphatidylinositol 3-kinases (PI3Ks); C2 domain present in all classes ...
 689-847 7.71e-22

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


Pssm-ID: 176026  Cd Length: 156  Bit Score: 93.58  E-value: 7.71e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  689 HLQFTLFAVHGIPATWVSSFE------KYYLMCALTHNNRNLFKPVQSKKVgtykSFFYHIKWDELINFPISVSLLPLEA 762
Cdd:cd08380      2 SLWDINFNLRIKIHGITNINLldsedlKLYVRVQLYHGGEPLCPPQSTKKV----PFSTSVTWNEWLTFDILISDLPREA 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  763 MLSLSLYGVlsqnannspdSNKQRKGPELLGKVSMPLFDFRRVLSRGSKLLSLWTSPQALQPGAAGKGrNPTEKIILQVD 842
Cdd:cd08380     78 RLCLSIYAV----------SEPGSKKEVPLGWVNVPLFDYKGKLRQGMITLNLWPGKKTDPRIACTPC-NNSNENSTRLL 146


                   ....*
gi 1207137159  843 FPSPA 847
Cdd:cd08380    147 IELPE 151
C2B_SLP_1-2-3-4 cd04020
C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically ...
 1566-1682 6.90e-21

C2 domain second repeat present in Synaptotagmin-like proteins 1-4; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. Slp1/JFC1 and Slp2/exophilin 4 promote granule docking to the plasma membrane. Additionally, their C2A domains are both Ca2+ independent, unlike the case in Slp3 and Slp4/granuphilin in which their C2A domains are Ca2+ dependent. It is thought that SHD (except for the Slp4-SHD) functions as a specific Rab27A/B-binding domain. In addition to Slps, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. It has been demonstrated that Slp3 and Slp4/granuphilin promote dense-core vesicle exocytosis. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175987 [Multi-domain]  Cd Length: 162  Bit Score: 91.23  E-value: 6.90e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1566 GEVKLSVSY--------------RNSTLFIMVMHIKDL-MSNDGADPNPYVKTYLLPDPHKTSKRKTKIARKTRNPTFNE 1630
Cdd:cd04020      2 GELKVALKYvppesegalkskkpSTGELHVWVKEAKNLpALKSGGTSDSFVKCYLLPDKSKKSKQKTPVVKKSVNPVWNH 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1207137159 1631 MLVYSGYSKETLKQRELQLSVLSAESLRENCYLGGITLCLKDFDLSRETVKW 1682
Cdd:cd04020     82 TFVYDGVSPEDLSQACLELTVWDHDKLSSNDFLGGVRLGLGTGKSYGQAVDW 133
PX smart00312
PhoX homologous domain, present in p47phox and p40phox; Eukaryotic domain of unknown function ...
 1437-1534 1.80e-20

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


Pssm-ID: 214610  Cd Length: 105  Bit Score: 88.17  E-value: 1.80e-20
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  1437 RYNPDKHYTYVIRILREGQSEPQFVFRTFDEFQELHNKLTILFQLWKLPGFPSKMVLGRT--HIKDVASKRKVELNSYVH 1514
Cdd:smart00312    6 KIGDGKHYYYVIEIETKTGLEEWTVSRRYSDFLELHSKLKKHFPRSILPPLPGKKLFGRLnnFSEEFIEKRRRGLEKYLQ 85

                            90       100
                    ....*....|....*....|
gi 1207137159  1515 NLMRSSTEVAQCDLIYTFFH 1534
Cdd:smart00312   86 SLLNHPELINHSEVVLEFLE 105
C2 pfam00168
C2 domain;
1578-1685 1.37e-19

C2 domain;


Pssm-ID: 425499 [Multi-domain]  Cd Length: 104  Bit Score: 85.45  E-value: 1.37e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1578 TLFIMVMHIKDLMSNDGAD-PNPYVKTYLLpdpHKTSKRKTKIARKTRNPTFNEMLVYSGYSKEtlkQRELQLSVLSAES 1656
Cdd:pfam00168    2 RLTVTVIEAKNLPPKDGNGtSDPYVKVYLL---DGKQKKKTKVVKNTLNPVWNETFTFSVPDPE---NAVLEIEVYDYDR 75

                           90       100
                   ....*....|....*....|....*....
gi 1207137159 1657 LRENCYLGGITLCLKDFDLSRETVKWYKL 1685
Cdd:pfam00168   76 FGRDDFIGEVRIPLSELDSGEGLDGWYPL 104
C2A_Synaptotagmin-7 cd08386
C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 1566-1686 1.45e-19

C2A domain first repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176032 [Multi-domain]  Cd Length: 125  Bit Score: 86.23  E-value: 1.45e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1566 GEVKLSVSY--RNSTLFIMVMHIKDLMSND-GADPNPYVKTYLLPDphKTSKRKTKIARKTRNPTFNEMLVYSGYSKETL 1642
Cdd:cd08386      3 GRIQFSVSYdfQESTLTLKILKAVELPAKDfSGTSDPFVKIYLLPD--KKHKLETKVKRKNLNPHWNETFLFEGFPYEKL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1207137159 1643 KQRELQLSVLSAESLRENCYLGGITLCLKDFDLSRETVKWYKLT 1686
Cdd:cd08386     81 QQRVLYLQVLDYDRFSRNDPIGEVSLPLNKVDLTEEQTFWKDLK 124
PIKKc_DNA-PK cd05172
Catalytic domain of DNA-dependent protein kinase; DNA-PK is comprised of a regulatory subunit, ...
 1133-1300 4.36e-18

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: 85.32  E-value: 4.36e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1133 DEINVMF--KVGEDLRQDMLALQMIRIMDRIWLQE----GLDLRIVNFKCISTGKDKGMVELVPSSETLRKIqveygvtg 1206
Cdd:cd05172     26 DEKEYKFlvKGGEDLRQDQRIQQLFDVMNNILASDpacrQRRLRIRTYQVIPMTSRLGLIEWVDNTTPLKEI-------- 97

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1207 sFKDKPLAEWLRKYNPAEDEYEKASENFIYTCAGCCVATYILGICDRHNDNIML-RSTGHMFHIDFGKFLGHA------- 1278
Cdd:cd05172     98 -LENDLLRRALLSLASSPEAFLALRSNFARSLAAMSICGYILGIGDRHLSNFLVdLSTGRLIGIDFGHAFGSAtqflpip 176

                          170       180       190
                   ....*....|....*....|....*....|.
gi 1207137159 1279 ---------QMIGSFKRDRAPFVLTSDMAYV 1300
Cdd:cd05172    177 elvpfrltrQLLNLLQPLDARGLLRSDMVHV 207
C2A_Synaptotagmin-15-17 cd08390
C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a ...
 1571-1685 1.23e-17

C2A domain first repeat present in Synaptotagmins 15 and 17; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. It is thought to be involved in the trafficking and exocytosis of secretory vesicles in non-neuronal tissues and is Ca2+ independent. Human synaptotagmin 15 has 2 alternatively spliced forms that encode proteins with different C-termini. The larger, SYT15a, contains a N-terminal TM region, a putative fatty-acylation site, and 2 tandem C terminal C2 domains. The smaller, SYT15b, lacks the C-terminal portion of the second C2 domain. Unlike most other synaptotagmins it is nearly absent in the brain and rather is found in the heart, lungs, skeletal muscle, and testis. Synaptotagmin 17 is located in the brain, kidney, and prostate and is thought to be a peripheral membrane protein. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176036 [Multi-domain]  Cd Length: 123  Bit Score: 80.38  E-value: 1.23e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1571 SVSYRNST--LFIMVMHIKDLMS--NDGADPNPYVKTYLLPDPHKTskRKTKIARKTRNPTFNEMLVYSgYSKETLKQRE 1646
Cdd:cd08390      6 SVQYDLEEeqLTVSLIKARNLPPrtKDVAHCDPFVKVCLLPDERRS--LQSKVKRKTQNPNFDETFVFQ-VSFKELQRRT 82

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1207137159 1647 LQLSVLSAESLRENCYLGGITLCLKDFDLSRETVKWYKL 1685
Cdd:cd08390     83 LRLSVYDVDRFSRHCIIGHVLFPLKDLDLVKGGVVWRDL 121
PIKKc cd05164
Catalytic domain of Phosphoinositide 3-kinase-related protein kinases; PIKK subfamily members ...
 1114-1328 1.39e-17

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: 83.47  E-value: 1.39e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1114 FNSNAVPLKIALVNADplGDEINVMFKVGEDLRQDMLALQMIRIMDRIWLQEG----LDLRIVNFKCISTGKDKGMVELV 1189
Cdd:cd05164     11 LASLQKPKKITILGSD--GKEYPFLVKGDDDLRKDERVMQLFQLLNTLLEKDKetrkRNLTIRTYSVVPLSSQSGLIEWV 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1190 PSSETLRKIqveygvtgsfkdkpLAEWLRKYNPAEDEYEKASENFIYTCAGCCVATYILGICDRHNDNIML-RSTGHMFH 1268
Cdd:cd05164     89 DNTTTLKPV--------------LKKWFNETFPDPTQWYEARSNYTKSTAVMSMVGYIIGLGDRHLENILIdTKTGEVVH 154

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1207137159 1269 IDF------GKFLGHAQMIgsfkrdraPFVLTSDMayvINGGErPTSRFQLFVDLCSQAYNLIRKH 1328
Cdd:cd05164    155 IDFgmifnkGKTLPVPEIV--------PFRLTRNI---INGMG-PTGVEGLFRKSCEQVLRVFRKH 208
PX_FISH cd06888
The phosphoinositide binding Phox Homology domain of Five SH protein; The PX domain is a ...
 1426-1535 1.57e-17

The phosphoinositide binding Phox Homology domain of Five SH protein; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. Five SH (FISH), also called Tks5, is a scaffolding protein and Src substrate that is localized in podosomes, which are electron-dense structures found in Src-transformed fibroblasts, osteoclasts, macrophages, and some invasive cancer cells. FISH contains an N-terminal PX domain and five Src homology 3 (SH3) domains. FISH binds and regulates some members of the ADAMs family of transmembrane metalloproteases, which function as sheddases and mediators of cell and matrix interactions. It is required for podosome formation, degradation of the extracellular matrix, and cancer cell invasion. This subfamily also includes proteins with a different number of SH3 domains than FISH, such as Tks4, which contains four SH3 domains instead of five. The Tks4 adaptor protein is required for the formation of functional podosomes. It has overlapping, but not identical, functions as FISH. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


Pssm-ID: 132798  Cd Length: 119  Bit Score: 80.16  E-value: 1.57e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1426 IRDASVFSFQKRYNPDKHYTYVIRILREGQSEpQFVFRTFDEFQELHNKLTILFQLWK---------LPGFPSKMVLGRT 1496
Cdd:cd06888      1 VKDVKVIDVEKRRAPSKHYVYIINVTWSDGSS-NVIYRRYSKFFDLQMQLLDKFPIEGgqkdpsqriIPFLPGKILFRRS 79

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1207137159 1497 HIKDVASKRKVELNSYVHNLMRSSTEVAQCDLIYTFFHP 1535
Cdd:cd06888     80 HIRDVAVKRLKPIDEYCKALVRLPPHISQCDEVLRFFEA 118
C2A_Rabphilin_Doc2 cd04035
C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 1566-1673 2.18e-17

C2 domain first repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176000 [Multi-domain]  Cd Length: 123  Bit Score: 80.02  E-value: 2.18e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1566 GEVKLSVSYR--NSTLFIMVMHIKDL--M-SNDGADPnpYVKTYLLPDPHKTSKRKTKIARKTRNPTFNEMLVYSGYSKE 1640
Cdd:cd04035      2 GTLEFTLLYDpaNSALHCTIIRAKGLkaMdANGLSDP--YVKLNLLPGASKATKLRTKTVHKTRNPEFNETLTYYGITEE 79

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1207137159 1641 TLKQRELQLSVLSaESLRENCYLGGITLCLKDF 1673
Cdd:cd04035     80 DIQRKTLRLLVLD-EDRFGNDFLGETRIPLKKL 111
C2A_SLP-3 cd08392
C2 domain first repeat present in Synaptotagmin-like protein 3; All Slp members basically ...
 1566-1685 6.14e-16

C2 domain first repeat present in Synaptotagmin-like protein 3; All Slp members basically share an N-terminal Slp homology domain (SHD) and C-terminal tandem C2 domains (named the C2A domain and the C2B domain) with the SHD and C2 domains being separated by a linker sequence of various length. SHD of Slp (except for the Slp4-SHD) function as a specific Rab27A/B-binding domain. In addition to Slp, rabphilin, Noc2, and Munc13-4 also function as Rab27-binding proteins. Little is known about the expression or localization of Slp3. The C2A domain of Slp3 is Ca2+ dependent. It has been demonstrated that Slp3 promotes dense-core vesicle exocytosis. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176038 [Multi-domain]  Cd Length: 128  Bit Score: 76.02  E-value: 6.14e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1566 GEVKLSVSYRNST--LFIMVMHIKDLMSNDGADP--NPYVKTYLLPDPHKTSKRKTKIARKTRNPTFNEMLVYSgYSKET 1641
Cdd:cd08392      2 GEIEFALHYNFRTscLEITIKACRNLAYGDEKKKkcHPYVKVCLLPDKSHNSKRKTAVKKGTVNPVFNETLKYV-VEADL 80

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1207137159 1642 LKQRELQLSVLSAESLRENCYLGGITLCLKDFDLSRETVK---WYKL 1685
Cdd:cd08392     81 LSSRQLQVSVWHSRTLKRRVFLGEVLIPLADWDFEDTDSQrflWYPL 127
C2_PKC_alpha_gamma cd04026
C2 domain in Protein Kinase C (PKC) alpha and gamma; A single C2 domain is found in PKC alpha ...
 1566-1685 4.23e-15

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


Pssm-ID: 175992 [Multi-domain]  Cd Length: 131  Bit Score: 73.45  E-value: 4.23e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1566 GEVKLSVSYRNSTLFIMVMHIKDLMSndgADPN----PYVKTYLLPDPHKTSKRKTKIARKTRNPTFNEMLVYsgYSKET 1641
Cdd:cd04026      2 GRIYLKISVKDNKLTVEVREAKNLIP---MDPNglsdPYVKLKLIPDPKNETKQKTKTIKKTLNPVWNETFTF--DLKPA 76

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1207137159 1642 LKQRELQLSVLSAESLRENCYLGGITLCLKdfDLSRETVK-WYKL 1685
Cdd:cd04026     77 DKDRRLSIEVWDWDRTTRNDFMGSLSFGVS--ELIKMPVDgWYKL 119
C2B_RIM1alpha cd04028
C2 domain second repeat contained in Rab3-interacting molecule (RIM) proteins; RIMs are ...
 1566-1685 4.31e-15

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


Pssm-ID: 175994 [Multi-domain]  Cd Length: 146  Bit Score: 73.96  E-value: 4.31e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1566 GEVKLSVSYRNSTLFIMVMHIKDLMSNDGAD--PNPYVKTYLLPDPHKTSKRKTKIARKTRNPTFNEMLVYsgysKETLK 1643
Cdd:cd04028     18 GDIQLGLYDKKGQLEVEVIRARGLVQKPGSKvlPAPYVKVYLLEGKKCIAKKKTKIARKTLDPLYQQQLVF----DVSPT 93

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1207137159 1644 QRELQLSVLSAESLREN-CYLGGITLCLKDFDLSRETVKWYKL 1685
Cdd:cd04028     94 GKTLQVIVWGDYGRMDKkVFMGVAQILLDDLDLSNLVIGWYKL 136
C2 smart00239
Protein kinase C conserved region 2 (CalB); Ca2+-binding motif present in phospholipases, ...
 1578-1682 4.96e-15

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


Pssm-ID: 214577 [Multi-domain]  Cd Length: 101  Bit Score: 72.52  E-value: 4.96e-15
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  1578 TLFIMVMHIKDLMSNDGAD-PNPYVKTYLLPDPHKtsKRKTKIARKTRNPTFNEMLVYSGYSKETlkqRELQLSVLSAES 1656
Cdd:smart00239    1 TLTVKIISARNLPPKDKGGkSDPYVKVSLDGDPKE--KKKTKVVKNTLNPVWNETFEFEVPPPEL---AELEIEVYDKDR 75

                            90       100
                    ....*....|....*....|....*.
gi 1207137159  1657 LRENCYLGGITLCLKDFDLSRETVKW 1682
Cdd:smart00239   76 FGRDDFIGQVTIPLSDLLLGGRHEKL 101
C2B_Rabphilin_Doc2 cd08384
C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons ...
 1567-1668 5.15e-15

C2 domain second repeat present in Rabphilin and Double C2 domain; Rabphilin is found neurons and in neuroendrocrine cells, while Doc2 is found not only in the brain but in tissues, including mast cells, chromaffin cells, and osteoblasts. Rabphilin and Doc2s share highly homologous tandem C2 domains, although their N-terminal structures are completely different: rabphilin contains an N-terminal Rab-binding domain (RBD),7 whereas Doc2 contains an N-terminal Munc13-1-interacting domain (MID). C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176030 [Multi-domain]  Cd Length: 133  Bit Score: 73.54  E-value: 5.15e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1567 EVKLSVSYRNSTLFIMVMHIKDLM---SNDGADPnpYVKTYLLPDPHKTSKRKTKIARKTRNPTFNEMLVYSgYSKETLK 1643
Cdd:cd08384      3 LVSLMYNTQRRGLIVGIIRCVNLAamdANGYSDP--FVKLYLKPDAGKKSKHKTQVKKKTLNPEFNEEFFYD-IKHSDLA 79

                           90       100
                   ....*....|....*....|....*
gi 1207137159 1644 QRELQLSVLSAESLRENCYLGGITL 1668
Cdd:cd08384     80 KKTLEITVWDKDIGKSNDYIGGLQL 104
C2B_Synaptotagmin cd00276
C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking ...
 1566-1664 1.67e-14

C2 domain second repeat present in Synaptotagmin; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. There are several classes of Synaptotagmins. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175975 [Multi-domain]  Cd Length: 134  Bit Score: 71.85  E-value: 1.67e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1566 GEVKLSVSYRNST--LFIMVMHIKDLMSNDG-ADPNPYVKTYLLPDPHKTSKRKTKIARKTRNPTFNEMLVYSgYSKETL 1642
Cdd:cd00276      1 GELLLSLSYLPTAerLTVVVLKARNLPPSDGkGLSDPYVKVSLLQGGKKLKKKKTSVKKGTLNPVFNEAFSFD-VPAEQL 79

                           90       100
                   ....*....|....*....|..
gi 1207137159 1643 KQRELQLSVLSAESLRENCYLG 1664
Cdd:cd00276     80 EEVSLVITVVDKDSVGRNEVIG 101
PX pfam00787
PX domain; PX domains bind to phosphoinositides.
 1451-1535 2.73e-14

PX domain; PX domains bind to phosphoinositides.


Pssm-ID: 459940  Cd Length: 84  Bit Score: 69.58  E-value: 2.73e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1451 LREGQSEPQFVFRTFDEFQELHNKLTILFQLWKLPGFPSKMVLGRTHiKDVASKRKVELNSYVHNLMRSStEVAQCDLIY 1530
Cdd:pfam00787    1 LPTFSLEEWSVRRRYSDFVELHKKLLRKFPSVIIPPLPPKRWLGRYN-EEFIEKRRKGLEQYLQRLLQHP-ELRNSEVLL 78


                   ....*
gi 1207137159 1531 TFFHP 1535
Cdd:pfam00787   79 EFLES 83
PIKKc_ATR cd00892
Catalytic domain of Ataxia telangiectasia and Rad3-related proteins; ATR is also referred to ...
 1107-1297 1.71e-13

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: 71.77  E-value: 1.71e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1107 NIKVcsfFNSNAVPLKIALVNADplGDEINVMFKVGEDLRQDMLALQMIRIMDRIWLQ----EGLDLRIVNFKCISTGKD 1182
Cdd:cd00892      7 EVEI---MPSLQKPKKITLVGSD--GKKYPFLCKPKDDLRKDARMMEFNTLINRLLSKdpesRRRNLHIRTYAVIPLNEE 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1183 KGMVELVPSSETLRKIQVEYgvtgsfkDKP-LAEWLRKYNPAEDEYEKASENFIYTCAGCCVATYILGICDRHNDNIMLR 1261
Cdd:cd00892     82 CGIIEWVPNTVTLRSILSTL-------YPPvLHEWFLKNFPDPTAWYEARNNYTRSTAVMSMVGYILGLGDRHGENILFD 154

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|..
gi 1207137159 1262 S-TGHMFHID----FGKflGHaqmigSFKR-DRAPFVLTSDM 1297
Cdd:cd00892    155 StTGDVVHVDfdclFDK--GL-----TLEVpERVPFRLTQNM 189
PX_domain cd06093
The Phox Homology domain, a phosphoinositide binding module; The PX domain is a ...
 1428-1533 4.97e-13

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


Pssm-ID: 132768 [Multi-domain]  Cd Length: 106  Bit Score: 67.00  E-value: 4.97e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1428 DASVFSFQKRYNPDKHYT-YVIRIlREGQSEPQFVFRTFDEFQELHNKLTILFQLWKLPGFPSKMVLGRtHIKDVASKRK 1506
Cdd:cd06093      1 SVSIPDYEKVKDGGKKYVvYIIEV-TTQGGEEWTVYRRYSDFEELHEKLKKKFPGVILPPLPPKKLFGN-LDPEFIEERR 78

                           90       100
                   ....*....|....*....|....*..
gi 1207137159 1507 VELNSYVHNLMrSSTEVAQCDLIYTFF 1533
Cdd:cd06093     79 KQLEQYLQSLL-NHPELRNSEELKEFL 104
C2A_Synaptotagmin-1-5-6-9-10 cd08385
C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a ...
 1566-1686 1.66e-12

C2A domain first repeat present in Synaptotagmins 1, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis as do synaptotagmins 5, 6, and 10. It is distinguished from the other synaptotagmins by having an N-glycosylated N-terminus. Synaptotagmins 5, 6, and 10, members of class 3 synaptotagmins, are located primarily in the brain and localized to the active zone and plasma membrane. They is distinguished from the other synaptotagmins by having disulfide bonds at its N-terminus. Synaptotagmin 6 also regulates the acrosome reaction, a unique Ca2+-regulated exocytosis, in sperm. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176031 [Multi-domain]  Cd Length: 124  Bit Score: 65.75  E-value: 1.66e-12
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1566 GEVKLSVSY--RNSTLFIMVMHIKDLMSND-GADPNPYVKTYLLPDPHKtsKRKTKIARKTRNPTFNEMLVYSGYSKEtL 1642
Cdd:cd08385      3 GKLQFSLDYdfQSNQLTVGIIQAADLPAMDmGGTSDPYVKVYLLPDKKK--KFETKVHRKTLNPVFNETFTFKVPYSE-L 79

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....
gi 1207137159 1643 KQRELQLSVLSAESLRENCYLGGITLCLKDFDLSRETVKWYKLT 1686
Cdd:cd08385     80 GNKTLVFSVYDFDRFSKHDLIGEVRVPLLTVDLGHVTEEWRDLE 123
PX_p40phox cd06882
The phosphoinositide binding Phox Homology domain of the p40phox subunit of NADPH oxidase; The ...
 1428-1534 1.23e-11

The phosphoinositide binding Phox Homology domain of the p40phox subunit of NADPH oxidase; The PX domain is a phosphoinositide binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. p40phox contains an N-terminal PX domain, a central SH3 domain that binds p47phox, and a C-terminal PB1 domain that interacts with p67phox. It is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox) which plays a crucial role in the cellular response to bacterial infection. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p40phox positively regulates NADPH oxidase in both phosphatidylinositol-3-phosphate (PI3P)-dependent and PI3P-independent manner. The PX domain is a phospholipid-binding module involved in the membrane targeting of proteins. The p40phox PX domain binds to PI3P, an abundant lipid in phagosomal membranes, playing an important role in the localization of NADPH oxidase. The PX domain of p40phox is also involved in protein-protein interaction.


Pssm-ID: 132792  Cd Length: 123  Bit Score: 63.61  E-value: 1.23e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1428 DASVFSFQKRYNPDKHYTYVIRILREGQSEpQFVFRTFDEFQELHNKLTILFQLWK--------LPGFPSKMVLGRThiK 1499
Cdd:cd06882      5 SATIADIEEKRGFTNYYVFVIEVKTKGGSK-YLIYRRYRQFFALQSKLEERFGPEAgssaydctLPTLPGKIYVGRK--A 81

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1207137159 1500 DVASKRKVELNSYVHNLMRSSTEVAQCDLIYTFFH 1534
Cdd:cd06882     82 EIAERRIPLLNRYMKELLSLPVWVLMDEDVRLFFY 116
C2 cd00030
C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed ...
 1579-1685 6.08e-11

C2 domain; The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 175973 [Multi-domain]  Cd Length: 102  Bit Score: 60.93  E-value: 6.08e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1579 LFIMVMHIKDLMSNDGAD-PNPYVKTYLLPdphkTSKRKTKIARKTRNPTFNEMLVYSGYSKETlkqRELQLSVLSAESL 1657
Cdd:cd00030      1 LRVTVIEARNLPAKDLNGkSDPYVKVSLGG----KQKFKTKVVKNTLNPVWNETFEFPVLDPES---DTLTVEVWDKDRF 73

                           90       100
                   ....*....|....*....|....*....
gi 1207137159 1658 RENCYLGGITLCLKDF-DLSRETVKWYKL 1685
Cdd:cd00030     74 SKDDFLGEVEIPLSELlDSGKEGELWLPL 102
C2_RGS-like cd08685
C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of ...
 1566-1685 8.80e-11

C2 domain of the Regulator Of G-Protein Signaling (RGS) family; This CD contains members of the regulator of G-protein signaling (RGS) family. RGS is a GTPase activating protein which inhibits G-protein mediated signal transduction. The protein is largely cytosolic, but G-protein activation leads to translocation of this protein to the plasma membrane. A nuclear form of this protein has also been described, but its sequence has not been identified. There are multiple alternatively spliced transcript variants in this family with some members having additional domains (ex. PDZ and RGS) downstream of the C2 domain. The C2 domain was first identified in PKC. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions.


Pssm-ID: 176067 [Multi-domain]  Cd Length: 119  Bit Score: 60.93  E-value: 8.80e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1566 GEVKLSVSYRNSTLFIMVMHIKDLMSNDGADPNPYVKTYLLPDPHKTSKRKTKIARKTRNPTFNEMLVYSgySKETLKQR 1645
Cdd:cd08685      1 GQLKLSIEGQNRKLTLHVLEAKGLRSTNSGTCNSYVKISLSPDKEVRFRQKTSTVPDSANPLFHETFSFD--VNERDYQK 78

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|.
gi 1207137159 1646 ELQLSVLSAESLRENC-YLGGITLCLKDFDLSRETVKWYKL 1685
Cdd:cd08685     79 RLLVTVWNKLSKSRDSgLLGCMSFGVKSIVNQKEISGWYYL 119
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
 1141-1272 4.87e-10

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: 59.38  E-value: 4.87e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1141 VGEDLRQDMLALQMIRIMDriwlqegldLRIVNFK--CISTGKDKGMVELVPSSETLRKIQVEYgvtgsfkdkplaewlr 1218
Cdd:cd13968     33 EGEDLESEMDILRRLKGLE---------LNIPKVLvtEDVDGPNILLMELVKGGTLIAYTQEEE---------------- 87

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*.
gi 1207137159 1219 kynpaedEYEKASENFIYTCAGCCVATYI--LGICDRHNDNIMLRSTGHMFHIDFG 1272
Cdd:cd13968     88 -------LDEKDVESIMYQLAECMRLLHSfhLIHRDLNNDNILLSEDGNVKLIDFG 136
C2B_Synaptotagmin-12 cd08406
C2 domain second repeat present in Synaptotagmin 12; Synaptotagmin is a membrane-trafficking ...
 1565-1635 9.39e-10

C2 domain second repeat present in Synaptotagmin 12; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 12, a member of class 6 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmins 8 and 13, do not have any consensus Ca2+ binding sites. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176051 [Multi-domain]  Cd Length: 136  Bit Score: 58.26  E-value: 9.39e-10
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207137159 1565 EGEVKLSVSYRNST--LFIMVMHIKDL-MSNDGADPNPYVKTYLLPDPHKTSKRKTKIARKTRNPTFNEMLVYS 1635
Cdd:cd08406      1 VGEILLSLSYLPTAerLTVVVVKARNLvWDNGKTTADPFVKVYLLQDGRKISKKKTSVKRDDTNPIFNEAMIFS 74
PX_UP2_fungi cd06869
The phosphoinositide binding Phox Homology domain of uncharacterized fungal proteins; The PX ...
 1442-1534 2.51e-09

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


Pssm-ID: 132779  Cd Length: 119  Bit Score: 56.52  E-value: 2.51e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1442 KHYTYVIRILREGQSEP-QFVFRTFDEFQELHNKLTILFQLWKLPGFPSKMVLGRthikdvaSKRKVELNSYVHNLMrSS 1520
Cdd:cd06869     32 HHYEFIIRVRREGEEYRtIYVARRYSDFKKLHHDLKKEFPGKKLPKLPHKDKLPR-------EKLRLSLRQYLRSLL-KD 103

                           90
                   ....*....|....
gi 1207137159 1521 TEVAQCDLIYTFFH 1534
Cdd:cd06869    104 PEVAHSSILQEFLT 117
C2_PI3K_class_III cd08397
C2 domain present in class III phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 712-821 2.89e-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: 57.64  E-value: 2.89e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  712 YLMCALTHNNRNLFKPVQSkkvgTYKSFFYHIKWDELINFPISVSLLPLEAMLSLSLYGVlsqnannspdsNKQRKgPEL 791
Cdd:cd08397     33 FVTCQVFDDGKPLTLPVQT----SYKPFKNRRNWNEWLTLPIKYSDLPRNSQLAITIWDV-----------SGTGK-AVP 96

                           90       100       110
                   ....*....|....*....|....*....|
gi 1207137159  792 LGKVSMPLFDFRRVLSRGSKLLSLWTSPQA 821
Cdd:cd08397     97 FGGTTLSLFNKDGTLRRGRQKLRVWPDVEA 126
C2A_Synaptotagmin-4-11 cd08388
C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a ...
 1569-1678 3.19e-09

C2A domain first repeat present in Synaptotagmins 4 and 11; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmins 4 and 11, class 4 synaptotagmins, are located in the brain. Their functions are unknown. They are distinguished from the other synaptotagmins by having and Asp to Ser substitution in their C2A domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176034 [Multi-domain]  Cd Length: 128  Bit Score: 56.59  E-value: 3.19e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1569 KLSVSYRNSTLFIMVMHIKDLMSNDG--ADPNPYVKTYLLPDphKTSKRKTKIARKTRNPTFNEMLVYSGYSKETLKQRE 1646
Cdd:cd08388      8 SLRYNSEKKALLVNIIECRDLPAMDEqsGTSDPYVKLQLLPE--KEHKVKTRVLRKTRNPVYDETFTFYGIPYNQLQDLS 85

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1207137159 1647 LQLSVLSAESLRENCYLGGITLCLKDFDLSRE 1678
Cdd:cd08388     86 LHFAVLSFDRYSRDDVIGEVVCPLAGADLLNE 117
PX_p47phox cd06887
The phosphoinositide binding Phox Homology domain of the p47phox subunit of NADPH oxidase; The ...
 1426-1533 3.29e-09

The phosphoinositide binding Phox Homology domain of the p47phox subunit of NADPH oxidase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. p47phox is a cytosolic subunit of the phagocytic NADPH oxidase complex (also called Nox2 or gp91phox), which plays a key role in the ability of phagocytes to defend against bacterial infections. NADPH oxidase catalyzes the transfer of electrons from NADPH to oxygen during phagocytosis forming superoxide and reactive oxygen species. p47phox is required for activation of NADH oxidase and plays a role in translocation. It contains an N-terminal PX domain, two Src Homology 3 (SH3) domains, and a C-terminal domain that contains PxxP motifs for binding SH3 domains. The PX domain of p47phox is unique in that it contains two distinct basic pockets on the membrane-binding surface: one preferentially binds phosphatidylinositol-3,4-bisphosphate [PI(3,4)P2] and is analogous to the PI3P-binding pocket of p40phox, while the other binds anionic phospholipids such as phosphatidic acid or phosphatidylserine. Simultaneous binding in the two pockets results in increased membrane affinity. The PX domain of p47phox is also involved in protein-protein interaction.


Pssm-ID: 132797  Cd Length: 118  Bit Score: 56.38  E-value: 3.29e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1426 IRDASVFSFQKRYNPDKHYTYVIRILREGQSEpQFVFRTFDEFQELHNKLTILFQL---------WKLPGFPSKMVLGRt 1496
Cdd:cd06887      1 IRHIALLGFEKRFVPSQHYVYMFLVKWQDLSE-KLVYRRFTEIYEFHKTLKEMFPIeagdinkenRIIPHLPAPKWFDG- 78

                           90       100       110
                   ....*....|....*....|....*....|....*..
gi 1207137159 1497 hiKDVASKRKVELNSYVHNLMRSSTEVAQCDLIYTFF 1533
Cdd:cd06887     79 --QRAAENRQGTLTEYCSTLLSLPPKISRCPHVLDFF 113
C2B_Synaptotagmin-7 cd08405
C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking ...
 1566-1668 3.48e-09

C2 domain second repeat present in Synaptotagmin 7; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 7, a member of class 2 synaptotagmins, is located in presynaptic plasma membranes in neurons, dense-core vesicles in endocrine cells, and lysosomes in fibroblasts. It has been shown to play a role in regulation of Ca2+-dependent lysosomal exocytosis in fibroblasts and may also function as a vesicular Ca2+-sensor. It is distinguished from the other synaptotagmins by having over 12 splice forms. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176050 [Multi-domain]  Cd Length: 136  Bit Score: 56.66  E-value: 3.48e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1566 GEVKLSVSYR--NSTLFIMVMHIKDLMSND-GADPNPYVKTYLLPDPHKTSKRKTKIARKTRNPTFNEMLVYSgYSKETL 1642
Cdd:cd08405      2 GELLLSLCYNptANRITVNIIKARNLKAMDiNGTSDPYVKVWLMYKDKRVEKKKTVIKKRTLNPVFNESFIFN-IPLERL 80

                           90       100
                   ....*....|....*....|....*.
gi 1207137159 1643 KQRELQLSVLSAESLRENCYLGGITL 1668
Cdd:cd08405     81 RETTLIITVMDKDRLSRNDLIGKIYL 106
C2B_Synaptotagmin-4 cd08404
C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking ...
 1566-1668 9.81e-09

C2 domain second repeat present in Synaptotagmin 4; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176049 [Multi-domain]  Cd Length: 136  Bit Score: 55.51  E-value: 9.81e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1566 GEVKLSVSYRNST--LFIMVMHIKDLMSNDGADP-NPYVKTYLLPDPHKTSKRKTKIARKTRNPTFNEMLVYSGYSKEtL 1642
Cdd:cd08404      2 GELLLSLCYQPTTnrLTVVVLKARHLPKMDVSGLaDPYVKVNLYYGKKRISKKKTHVKKCTLNPVFNESFVFDIPSEE-L 80

                           90       100
                   ....*....|....*....|....*.
gi 1207137159 1643 KQRELQLSVLSAESLRENCYLGGITL 1668
Cdd:cd08404     81 EDISVEFLVLDSDRVTKNEVIGRLVL 106
PIKKc_ATM cd05171
Catalytic domain of Ataxia Telangiectasia Mutated; ATM is critical in the response to DNA ...
 1139-1272 1.78e-08

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: 57.55  E-value: 1.78e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1139 FKVGEDLRQDMLALQMIRIMDrIWLQEGL-----DLRIVNFKCISTGKDKGMVELVPSSETLRKIQVEYGVTGSF----- 1208
Cdd:cd05171     34 VKGGDDLRQDAVMEQVFELVN-QLLKRDKetrkrKLRIRTYKVVPLSPRSGVLEFVENTIPLGEYLVGASSKSGAharyr 112

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1209 -KDKPLAEWLRKYNPAEDE--------YEKASENF-----------------------IYT--CAGCCVATYILGICDRH 1254
Cdd:cd05171    113 pKDWTASTCRKKMREKAKAsaeerlkvFDEICKNFkpvfrhfflekfpdpsdwferrlAYTrsVATSSIVGYILGLGDRH 192

                          170
                   ....*....|....*....
gi 1207137159 1255 NDNIML-RSTGHMFHIDFG 1272
Cdd:cd05171    193 LNNILIdQKTGELVHIDLG 211
C2A_Synaptotagmin-8 cd08387
C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking ...
 1566-1685 1.23e-07

C2A domain first repeat present in Synaptotagmin 8; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the first C2 repeat, C2A, and has a type-I topology.


Pssm-ID: 176033 [Multi-domain]  Cd Length: 124  Bit Score: 52.02  E-value: 1.23e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1566 GEVKLSVSYRNS--TLFIMVMHIKDLMSND---GADPnpYVKTYLLPDPHKTskRKTKIARKTRNPTFNEMLVYsGYSKE 1640
Cdd:cd08387      3 GELHFSLEYDKDmgILNVKLIQARNLQPRDfsgTADP--YCKVRLLPDRSNT--KQSKIHKKTLNPEFDESFVF-EVPPQ 77

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*
gi 1207137159 1641 TLKQRELQLSVLSAESLRENCYLGGITLCLKDFDLSRETVKWYKL 1685
Cdd:cd08387     78 ELPKRTLEVLLYDFDQFSRDECIGVVELPLAEVDLSEKLDLWRKI 122
PX_PI3K_C2_gamma cd06896
The phosphoinositide binding Phox Homology Domain of the Gamma Isoform of Class II ...
 1429-1533 1.39e-07

The phosphoinositide binding Phox Homology Domain of the Gamma Isoform of Class II Phosphoinositide 3-Kinases; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. The Phosphoinositide 3-Kinase (PI3K) family of enzymes catalyzes the phosphorylation of the 3-hydroxyl group of the inositol ring of phosphatidylinositol. PI3Ks play an important role in a variety of fundamental cellular processes, including cell motility, the Ras pathway, vesicle trafficking and secretion, immune cell activation and apoptosis. PI3Ks are divided into three main classes (I, II, and III) based on their substrate specificity, regulation, and domain structure. Class II PI3Ks preferentially use PI as a substrate to produce PI3P, but can also phosphorylate PI4P to produce PI(3,4)P2. They function as monomers and do not associate with any regulatory subunits. Class II enzymes contain an N-terminal Ras binding domain, a lipid binding C2 domain, a PI3K homology domain of unknown function, an ATP-binding cataytic domain, a PX domain, and a second C2 domain at the C-terminus. The class II gamma isoform, PI3K-C2gamma, is expressed in the liver, breast, and prostate. It's biological function remains unknown. The PX domain is involved in targeting of proteins to PI-enriched membranes, and may also be involved in protein-protein interaction.


Pssm-ID: 132806  Cd Length: 101  Bit Score: 51.06  E-value: 1.39e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1429 ASVFSFQKRYNpdkhYTYVIRILrEGQSEPQFVFRTFDEFQELHNKLTILFQLWKLPGFPSKMVLGRThikDVASKRKVE 1508
Cdd:cd06896      2 ATILGFSKKSS----NLYLVQVT-QSCNLVSLTEKSFEQFSELHSQLQKQFPSLALPEFPHWWHLPFT---DSDHKRVRD 73

                           90       100
                   ....*....|....*....|....*
gi 1207137159 1509 LNSYVHNLMRSSTEVAQCDLIYTFF 1533
Cdd:cd06896     74 LNHYLEQLLSGSREVANSDCVLSFF 98
C2B_Synaptotagmin-1 cd08402
C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking ...
 1566-1668 1.47e-07

C2 domain second repeat present in Synaptotagmin 1; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 1, a member of the class 1 synaptotagmins, is located in the brain and endocranium and localized to the synaptic vesicles and secretory granules. It functions as a Ca2+ sensor for fast exocytosis. It, like synaptotagmin-2, has an N-glycosylated N-terminus. Synaptotagmin 4, a member of class 4 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmin-11, has an Asp to Ser substitution in its C2A domain. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176047 [Multi-domain]  Cd Length: 136  Bit Score: 52.02  E-value: 1.47e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1566 GEVKLSVSYR--NSTLFIMVMHIKDLMSND-GADPNPYVKTYLLPDPHKTSKRKTKIARKTRNPTFNEMLVYSgYSKETL 1642
Cdd:cd08402      2 GDICFSLRYVptAGKLTVVILEAKNLKKMDvGGLSDPYVKIHLMQNGKRLKKKKTTIKKRTLNPYYNESFSFE-VPFEQI 80

                           90       100
                   ....*....|....*....|....*.
gi 1207137159 1643 KQRELQLSVLSAESLRENCYLGGITL 1668
Cdd:cd08402     81 QKVHLIVTVLDYDRIGKNDPIGKVVL 106
C2_PI3K_class_I_beta_delta cd08693
C2 domain present in class I beta and delta phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 716-819 2.28e-07

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: 52.31  E-value: 2.28e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  716 ALTHNNRNLFKPVQSKKV-GTYKSFfyhikWDELINFPISVSLLPLEAMLSLSLYGVL----SQNANNSPDSNKQRKGPE 790
Cdd:cd08693     34 GLFHGGESLCKTVKTSEVsGKNDPV-----WNETLEFDINVCDLPRMARLCFAIYEVSkkakGKRSRKNQTKKKKKKDDN 108

                           90       100
                   ....*....|....*....|....*....
gi 1207137159  791 LLGKVSMPLFDFRRVLSRGSKLLSLWTSP 819
Cdd:cd08693    109 PIAWVNTMVFDYKGQLKTGDHTLYMWTYA 137
C2B_Synaptotagmin-3-5-6-9-10 cd08403
C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a ...
 1566-1664 3.12e-07

C2 domain second repeat present in Synaptotagmins 3, 5, 6, 9, and 10; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 3, a member of class 3 synaptotagmins, is located in the brain and localized to the active zone and plasma membrane. It functions as a Ca2+ sensor for fast exocytosis. It, along with synaptotagmins 5,6, and 10, has disulfide bonds at its N-terminus. Synaptotagmin 9, a class 5 synaptotagmins, is located in the brain and localized to the synaptic vesicles. It is thought to be a Ca2+-sensor for dense-core vesicle exocytosis. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176048 [Multi-domain]  Cd Length: 134  Bit Score: 50.97  E-value: 3.12e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1566 GEVKLSVSY--RNSTLFIMVMHIKDLMSNDGAD-PNPYVKTYLLPDPHKTSKRKTKIARKTRNPTFNEMLVYSgYSKETL 1642
Cdd:cd08403      1 GELMFSLCYlpTAGRLTLTIIKARNLKAMDITGfSDPYVKVSLMCEGRRLKKKKTSVKKNTLNPTYNEALVFD-VPPENV 79

                           90       100
                   ....*....|....*....|..
gi 1207137159 1643 KQRELQLSVLSAESLRENCYLG 1664
Cdd:cd08403     80 DNVSLIIAVVDYDRVGHNELIG 101
PIKKc_TOR cd05169
Catalytic domain of Target of Rapamycin; TOR contains a rapamycin binding domain, a catalytic ...
 1185-1272 3.25e-07

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: 53.64  E-value: 3.25e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1185 MVELVPSSETLRKIQ-VE---YGVTGSfKDKPLAE--WLRKYNpAEDEYEKASeNFIYTCAGCCVATYILGICDRHNDNI 1258
Cdd:cd05169    116 MLQMAPDYDNLTLIQkVEvfeYALENT-PGDDLRRvlWLKSPS-SEAWLERRT-NFTRSLAVMSMVGYILGLGDRHPSNI 192

                           90
                   ....*....|....*
gi 1207137159 1259 ML-RSTGHMFHIDFG 1272
Cdd:cd05169    193 MLdRLTGKVIHIDFG 207
C2B_Synaptotagmin-13 cd08407
C2 domain second repeat present in Synaptotagmin 13; Synaptotagmin is a membrane-trafficking ...
 1566-1670 1.60e-06

C2 domain second repeat present in Synaptotagmin 13; Synaptotagmin is a membrane-trafficking protein characterized by a N-terminal transmembrane region, a linker, and 2 C-terminal C2 domains. Synaptotagmin 13, a member of class 6 synaptotagmins, is located in the brain. It functions are unknown. It, like synaptotagmins 8 and 12, does not have any consensus Ca2+ binding sites. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176052 [Multi-domain]  Cd Length: 138  Bit Score: 49.21  E-value: 1.60e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1566 GEVKLSVSYRNST--LFIMVMHIKDLMSN-----DGADPNpyVKTYLLPDPHKTSKRKTKIARKTRNPTFNEMLVYSgYS 1638
Cdd:cd08407      2 GEVLLSISYLPAAnrLLVVVIKAKNLHSDqlkllLGIDVS--VKVTLKHQNAKLKKKQTKRAKHKINPVWNEMIMFE-LP 78

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1207137159 1639 KETLKQRELQLSVLSAESLRENCYLGGITLCL 1670
Cdd:cd08407     79 SELLAASSVELEVLNQDSPGQSLPLGRCSLGL 110
C2B_Munc13-like cd04009
C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are ...
 1565-1630 2.50e-06

C2 domain second repeat in Munc13 (mammalian uncoordinated)-like proteins; C2-like domains are thought to be involved in phospholipid binding in a Ca2+ independent manner in both Unc13 and Munc13. Caenorabditis elegans Unc13 has a central domain with sequence similarity to PKC, which includes C1 and C2-related domains. Unc13 binds phorbol esters and DAG with high affinity in a phospholipid manner. Mutations in Unc13 results in abnormal neuronal connections and impairment in cholinergic neurotransmission in the nematode. Munc13 is the mammalian homolog which are expressed in the brain. There are 3 isoforms (Munc13-1, -2, -3) and are thought to play a role in neurotransmitter release and are hypothesized to be high-affinity receptors for phorbol esters. Unc13 and Munc13 contain both C1 and C2 domains. There are two C2 related domains present, one central and one at the carboxyl end. Munc13-1 contains a third C2-like domain. Munc13 interacts with syntaxin, synaptobrevin, and synaptotagmin suggesting a role for these as scaffolding proteins. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the third C2 repeat, C2C, and has a type-II topology.


Pssm-ID: 175976 [Multi-domain]  Cd Length: 133  Bit Score: 48.39  E-value: 2.50e-06
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1207137159 1565 EGEVKLSVSYRNS--TLFIMVMHIKDLM---SNDGADPnpYVKTYLLPdPHK---TSKRKTKIARKTRNPTFNE 1630
Cdd:cd04009      2 YGVLTVKAYYRASeqSLRVEILNARNLLpldSNGSSDP--FVKVELLP-RHLfpdVPTPKTQVKKKTLFPLFDE 72
PX_NoxO1 cd06889
The phosphoinositide binding Phox Homology domain of Nox Organizing protein 1; The PX domain ...
 1440-1535 1.34e-05

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


Pssm-ID: 132799  Cd Length: 121  Bit Score: 46.23  E-value: 1.34e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1440 PDKHYTYVIRILREGQSEpQFVFRTFDEFQELHNKLTILFQLWK---------LPGFPSKMVLGRthiKDVASKRKVE-- 1508
Cdd:cd06889     16 KRRHKTYMFSVLWSDGSE-LFVYRSLEEFRKLHKQLKEKFPVEAgllrssdrvLPKFKDAPSLGS---LKGSTSRSLArl 91

                           90       100
                   ....*....|....*....|....*....
gi 1207137159 1509 --LNSYVHNLMRSSTEVAQCDLIYTFFHP 1535
Cdd:cd06889     92 klLETYCQELLRLDEKVSRSPEVIQFFAP 120
C2B_RasA3 cd04010
C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of ...
 1598-1685 1.99e-05

C2 domain second repeat present in RAS p21 protein activator 3 (RasA3); RasA3 are members of GTPase activating protein 1 (GAP1), a Ras-specific GAP, which suppresses Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. RasA3 contains an N-terminal C2 domain, a Ras-GAP domain, a plextrin homology (PH)-like domain, and a Bruton's Tyrosine Kinase (BTK) zinc binding domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 175977 [Multi-domain]  Cd Length: 148  Bit Score: 46.24  E-value: 1.99e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1598 NPYVKTYLLPDPHKTSKRKTKIARKTRNPTFNEMLV------------YSGYSKETLKQRELQLSVLSAESLRENCYLGG 1665
Cdd:cd04010     20 DPYASVTLIYSNKKQDTKRTKVKKKTNNPQFDEAFYfdvtidsspekkQFEMPEEDAEKLELRVDLWHASMGGGDVFLGE 99

                           90       100
                   ....*....|....*....|.
gi 1207137159 1666 ITLCLKDFDLSRETVK-WYKL 1685
Cdd:cd04010    100 VRIPLRGLDLQAGSHQaWYFL 120
C2B_Synaptotagmin-14_16 cd08408
C2 domain second repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are ...
 1567-1668 4.16e-05

C2 domain second repeat present in Synaptotagmins 14 and 16; Synaptotagmin 14 and 16 are membrane-trafficking proteins in specific tissues outside the brain. Both of these contain C-terminal tandem C2 repeats, but only Synaptotagmin 14 has an N-terminal transmembrane domain and a putative fatty-acylation site. Previously all synaptotagmins were thought to be calcium sensors in the regulation of neurotransmitter release and hormone secretion, but it has been shown that not all of them bind calcium and this is indeed the case here. Of the 17 identified synaptotagmins only 8 bind calcium (1-3, 5-7, 9, 10). The function of the two C2 domains that bind calcium are: regulating the fusion step of synaptic vesicle exocytosis (C2A) and binding to phosphatidyl-inositol-3,4,5-triphosphate (PIP3) in the absence of calcium ions and to phosphatidylinositol bisphosphate (PIP2) in their presence (C2B). C2B also regulates also the recycling step of synaptic vesicles. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-I topology.


Pssm-ID: 176053 [Multi-domain]  Cd Length: 138  Bit Score: 45.05  E-value: 4.16e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1567 EVKLSVSYRNSTLFIMVMHIKDL---MSNDGADPNPYVKTYLL-PDPHKTSKRKTKIARKTRNPTFNEMLVYSgYSKETL 1642
Cdd:cd08408      3 ELLLGLEYNALTGRLSVEVIKGSnfkNLAMNKAPDTYVKLTLLnSDGQEISKSKTSIRRGQPDPEFKETFVFQ-VALFQL 81

                           90       100
                   ....*....|....*....|....*.
gi 1207137159 1643 KQRELQLSVLSAESLRENCYLGGITL 1668
Cdd:cd08408     82 SEVTLMFSVYNKRKMKRKEMIGWFSL 107
C2_PI3K_class_I_alpha cd08398
C2 domain present in class I alpha phosphatidylinositol 3-kinases (PI3Ks); PI3Ks (AKA ...
 702-843 4.95e-05

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


Pssm-ID: 176043  Cd Length: 158  Bit Score: 45.55  E-value: 4.95e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  702 ATWVS--SFEKYYLMCALTHNNRNLFKPVQSKKVGTYKSffyhiKWDELINFPISVSLLPLEAMLSLSLYGVlsqnanns 779
Cdd:cd08398     17 ATYVNvnDIDKIYVRTGIYHGGEPLCDNVNTQRVPCSNP-----RWNEWLDYDIYIPDLPRSARLCLSICSV-------- 83

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207137159  780 pdsnKQRKGPE----LLGKVSMPLFDFRRVLSRGSKLLSLWTSPQA----LQPgAAGKGRNPT-EKIILQVDF 843
Cdd:cd08398     84 ----KGRKGAKeehcPLAWGNINLFDYTDTLVSGKMALNLWPVPHGledlLNP-IGVTGSNPNkDTPCLELEF 151
PIKKc_SMG1 cd05170
Catalytic domain of Suppressor of Morphogenetic effect on Genitalia-1; SMG-1 plays a critical ...
 1213-1271 6.95e-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: 46.86  E-value: 6.95e-05
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1213 LAEWLRKynpaedeyekaSENFIYTCAGCCVATYILGICDRHNDNIMLR-STGHMFHIDF 1271
Cdd:cd05170    184 SAEWWRV-----------TQRFARSLAVMSMIGYIIGLGDRHLDNILVDlSTGEVVHIDY 232
C2B_RasGAP cd08675
C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras ...
 1598-1685 1.02e-04

C2 domain second repeat of Ras GTPase activating proteins (GAPs); RasGAPs suppress Ras function by enhancing the GTPase activity of Ras proteins resulting in the inactive GDP-bound form of Ras. In this way it can control cellular proliferation and differentiation. The proteins here all contain two tandem C2 domains, a Ras-GAP domain, and a pleckstrin homology (PH)-like domain. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. Members here have a type-I topology.


Pssm-ID: 176057 [Multi-domain]  Cd Length: 137  Bit Score: 43.90  E-value: 1.02e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1598 NPYVKTYLLpDPHKTSKRKTKIARKTRNPTFNEMLVY------------SGYSKETLKQRELQLSVLSAESLRENCYLGG 1665
Cdd:cd08675     20 DPFARVTLN-YSSKTDTKRTKVKKKTNNPRFDEAFYFeltigfsyekksFKVEEEDLEKSELRVELWHASMVSGDDFLGE 98

                           90       100
                   ....*....|....*....|
gi 1207137159 1666 ITLCLKDFDLSRETVKWYKL 1685
Cdd:cd08675     99 VRIPLQGLQQAGSHQAWYFL 118
PX_SNX13 cd06873
The phosphoinositide binding Phox Homology domain of Sorting Nexin 13; The PX domain is a ...
 1446-1535 2.65e-04

The phosphoinositide binding Phox Homology domain of Sorting Nexin 13; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX13, also called RGS-PX1, contains an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs. It specifically binds to the stimulatory subunit of the heterotrimeric G protein G(alpha)s, serving as its GTPase activating protein, through the RGS domain. It preferentially binds phosphatidylinositol-3-phosphate (PI3P) through the PX domain and is localized in early endosomes. SNX13 is involved in endosomal sorting of EGFR into multivesicular bodies (MVB) for delivery to the lysosome.


Pssm-ID: 132783  Cd Length: 120  Bit Score: 42.26  E-value: 2.65e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1446 YVIRILREGQSEPQFVFRTFDEFQELHNKLTILF-QLWKLPgFPSKMVLGRTHiKDVASKRKVELNSYVHNLMRSStEVA 1524
Cdd:cd06873     28 SVTRIYPNGQEESWHVYRRYSDFHDLHMRLKEKFpNLSKLS-FPGKKTFNNLD-RAFLEKRRKMLNQYLQSLLNPE-VLD 104

                           90
                   ....*....|....*
gi 1207137159 1525 QCD----LIYTFFHP 1535
Cdd:cd06873    105 ANPglqeIVLDFLEP 119
PX_Bem1p cd06890
The phosphoinositide binding Phox Homology domain of Bem1p; The PX domain is a ...
 1428-1535 3.46e-04

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


Pssm-ID: 132800  Cd Length: 112  Bit Score: 41.89  E-value: 3.46e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1428 DASVFSFQKRynpDKHYTYVIRILREGQSEpQFVFRTFDEFQELHNKLTILFQLWKLPGfPSKMVLG-----RTHIKD-- 1500
Cdd:cd06890      2 SASVESVLLE---DNRYWYRVRATLSDGKT-RYLCRYYQDFYKLHIALLDLFPAEAGRN-SSKRILPylpgpVTDVVNds 76

                           90       100       110
                   ....*....|....*....|....*....|....*
gi 1207137159 1501 VASKRKVELNSYVHNLMRSSTEVAQCDLIYTFFHP 1535
Cdd:cd06890     77 ISLKRLNDLNEYLNELINLPAYIQTSEVVRDFFAN 111
PX_RUN cd07277
The phosphoinositide binding Phox Homology domain of uncharacterized proteins containing PX ...
 1440-1517 3.47e-04

The phosphoinositide binding Phox Homology domain of uncharacterized proteins containing PX and RUN domains; The PX domain is a phosphoinositide (PI) binding module involved in targeting proteins to PI-enriched membranes. Members in this subfamily are uncharacterized proteins containing an N-terminal RUN domain and a C-terminal PX domain. PX domain harboring proteins have been implicated in highly diverse functions such as cell signaling, vesicular trafficking, protein sorting, lipid modification, cell polarity and division, activation of T and B cells, and cell survival. In addition to protein-lipid interaction, the PX domain may also be involved in protein-protein interaction. The RUN domain is found in GTPases in the Rap and Rab families and may play a role in Ras-like signaling pathways.


Pssm-ID: 132810  Cd Length: 118  Bit Score: 41.95  E-value: 3.47e-04
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207137159 1440 PDKHYTYVIRIlREGQSEPQfVFRTFDEFQELHNKLTILFQLWKLPGFPSKMVLGRTHIKDVASKRKvELNSYVHNLM 1517
Cdd:cd07277     15 SDAHHVYQVYI-RIRDDEWN-VYRRYSEFYELHKKLKKKFPVVRSFDFPPKKAIGNKDAKFVEERRK-RLQVYLRRVV 89
DUF5585 pfam17823
Family of unknown function (DUF5585); This is a family of unknown function found in chordata.
 140-243 3.77e-04

Family of unknown function (DUF5585); This is a family of unknown function found in chordata.


Pssm-ID: 465521 [Multi-domain]  Cd Length: 506  Bit Score: 44.95  E-value: 3.77e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159  140 HAFNPSSFHWTPTPTHAQTPIFPSAPFAKPPCSFQNGFSPAMSPFIPPTPFLSFT---PIQPPAALVYSQPAVTPEMAKL 216
Cdd:pfam17823  276 HARRLSPAKHMPSDTMARNPAAPMGAQAQGPIIQVSTDQPVHNTAGEPTPSPSNTtlePNTPKSVASTNLAVVTTTKAQA 355

                           90       100
                   ....*....|....*....|....*..
gi 1207137159  217 FDKIASTSEYLKNGRSSSMETESASVK 243
Cdd:pfam17823  356 KEPSASPVPVLHTSMIPEVEATSPTTQ 382
Amelogenin smart00818
Amelogenins, cell adhesion proteins, play a role in the biomineralisation of teeth; They seem ...
 137-207 4.62e-04

Amelogenins, cell adhesion proteins, play a role in the biomineralisation of teeth; They seem to regulate formation of crystallites during the secretory stage of tooth enamel development and are thought to play a major role in the structural organisation and mineralisation of developing enamel. The extracellular matrix of the developing enamel comprises two major classes of protein: the hydrophobic amelogenins and the acidic enamelins. Circular dichroism studies of porcine amelogenin have shown that the protein consists of 3 discrete folding units: the N-terminal region appears to contain beta-strand structures, while the C-terminal region displays characteristics of a random coil conformation. Subsequent studies on the bovine protein have indicated the amelogenin structure to contain a repetitive beta-turn segment and a "beta-spiral" between Gln112 and Leu138, which sequester a (Pro, Leu, Gln) rich region. The beta-spiral offers a probable site for interactions with Ca2+ ions. Muatations in the human amelogenin gene (AMGX) cause X-linked hypoplastic amelogenesis imperfecta, a disease characterised by defective enamel. A 9bp deletion in exon 2 of AMGX results in the loss of codons for Ile5, Leu6, Phe7 and Ala8, and replacement by a new threonine codon, disrupting the 16-residue (Met1-Ala16) amelogenin signal peptide.


Pssm-ID: 197891 [Multi-domain]  Cd Length: 165  Bit Score: 42.85  E-value: 4.62e-04
                            10        20        30        40        50        60        70
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1207137159   137 PGGHAFNPSSFHWTPTPTHAQTPIFPSAPFAKPPCSFQNGFSP--AMSPFIPPTPFLSFTPIQPPAALVYSQP 207
Cdd:smart00818   77 PGQHSMTPTQHHQPNLPQPAQQPFQPQPLQPPQPQQPMQPQPPvhPIPPLPPQPPLPPMFPMQPLPPLLPDLP 149
PX_KIF16B_SNX23 cd06874
The phosphoinositide binding Phox Homology domain of KIF16B kinesin or Sorting Nexin 23; The ...
 1441-1538 8.55e-04

The phosphoinositide binding Phox Homology domain of KIF16B kinesin or Sorting Nexin 23; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions such as cell signaling, vesicular trafficking, protein sorting, and lipid modification, among others. KIF16B, also called sorting nexin 23 (SNX23), is a family-3 kinesin which harbors an N-terminal kinesin motor domain containing ATP and microtubule binding sites, a ForkHead Associated (FHA) domain, and a C-terminal PX domain. The PX domain of KIF16B binds to phosphatidylinositol-3-phosphate (PI3P) in early endosomes and plays a role in the transport of early endosomes to the plus end of microtubules. By regulating early endosome plus end motility, KIF16B modulates the balance between recycling and degradation of receptors. SNXs make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway.


Pssm-ID: 132784  Cd Length: 127  Bit Score: 41.21  E-value: 8.55e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1441 DKHYTYVIRILREGqsEPQFVFRTFDEFQELHNKLTILF-QLWKLPgFPSKMVLGRTHiKDVASKRKVELNSYVHNLMRS 1519
Cdd:cd06874     16 DEHFEFEVKITVLD--ETWTVFRRYSRFRELHKTMKLKYpEVAALE-FPPKKLFGNKS-ERVAKERRRQLETYLRNFFSV 91

                           90
                   ....*....|....*....
gi 1207137159 1520 STEVAQCDLIYTFFHPIAR 1538
Cdd:cd06874     92 CLKLPACPLYPKVGRTLSK 110
PX_SNX22 cd06880
The phosphoinositide binding Phox Homology domain of Sorting Nexin 22; The PX domain is a ...
 1430-1518 9.54e-04

The phosphoinositide binding Phox Homology domain of Sorting Nexin 22; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX22 may be involved in recruiting other proteins to the membrane via protein-protein and protein-ligand interaction. The biological function of SNX22 is not yet known.


Pssm-ID: 132790  Cd Length: 110  Bit Score: 40.34  E-value: 9.54e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1430 SVFSFQKRYNPDK--HYTYVIRILREGQSEpqFVFRTFDEFQELHNKLTilfQLWKLPGFPSKMVlgRTHIKDVASKRKV 1507
Cdd:cd06880      4 SIPSYRLEVDESEkpYTVFTIEVLVNGRRH--TVEKRYSEFHALHKKLK---KSIKTPDFPPKRV--RNWNPKVLEQRRQ 76

                           90
                   ....*....|.
gi 1207137159 1508 ELNSYVHNLMR 1518
Cdd:cd06880     77 GLEAYLQGLLK 87
PX_CISK cd06870
The phosphoinositide binding Phox Homology Domain of Cytokine-Independent Survival Kinase; The ...
 1441-1518 2.29e-03

The phosphoinositide binding Phox Homology Domain of Cytokine-Independent Survival Kinase; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Cytokine-independent survival kinase (CISK), also called Serum- and Glucocorticoid-induced Kinase 3 (SGK3), plays a role in cell growth and survival. It is expressed in most tissues and is most abundant in the embryo and adult heart and spleen. It was originally discovered in a screen for antiapoptotic genes. It phosphorylates and inhibits the proapoptotic proteins, Bad and FKHRL1. CISK/SGK3 also regulates many transporters, ion channels, and receptors. It plays a critical role in hair follicle morphogenesis and hair cycling. N-terminal to a catalytic kinase domain, CISK contains a PX domain which binds highly phosphorylated PIs, directs membrane localization, and regulates the enzyme's activity.


Pssm-ID: 132780  Cd Length: 109  Bit Score: 39.31  E-value: 2.29e-03
                           10        20        30        40        50        60        70
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207137159 1441 DKHYTyVIRILREGQSEPQFVFRTFDEFQELHNKLTILFQLWKLPgFPSKMVLGRTHIKDVASKRKVELNSYVHNLMR 1518
Cdd:cd06870     17 KKRFT-VYKVVVSVGRSSWFVFRRYAEFDKLYESLKKQFPASNLK-IPGKRLFGNNFDPDFIKQRRAGLDEFIQRLVS 92
C2D_Tricalbin-like cd04040
C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are ...
 1579-1687 2.78e-03

C2 domain fourth repeat present in Tricalbin-like proteins; 5 to 6 copies of the C2 domain are present in Tricalbin, a yeast homolog of Synaptotagmin, which is involved in membrane trafficking and sorting. 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 fifth C2 repeat, C2E, and has a type-II topology.


Pssm-ID: 176005 [Multi-domain]  Cd Length: 115  Bit Score: 39.09  E-value: 2.78e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1579 LFIMVMHIKDLMSndgADPN----PYVKTYLlpDPHKTSKrkTKIARKTRNPTFNEMLvysgysketlkqrELQLSVLSA 1654
Cdd:cd04040      1 LTVDVISAENLPS---ADRNgksdPFVKFYL--NGEKVFK--TKTIKKTLNPVWNESF-------------EVPVPSRVR 60

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|...
gi 1207137159 1655 ESLRENCY----------LGGITLCLKDFDLSRETVKWYKLTT 1687
Cdd:cd04040     61 AVLKVEVYdwdrggkddlLGSAYIDLSDLEPEETTELTLPLDG 103
C2A_MCTP_PRT_plant cd04022
C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); ...
 1579-1685 3.08e-03

C2 domain first repeat found in Multiple C2 domain and Transmembrane region Proteins (MCTP); plant subset; MCTPs are involved in Ca2+ signaling at the membrane. Plant-MCTPs are composed of a variable N-terminal sequence, four C2 domains, two transmembrane regions (TMRs), and a short C-terminal sequence. It is one of four protein classes that are anchored to membranes via a transmembrane region; the others being synaptotagmins, extended synaptotagmins, and ferlins. MCTPs are the only membrane-bound C2 domain proteins that contain two functional TMRs. MCTPs are unique in that they bind Ca2+ but not phospholipids. 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-II topology.


Pssm-ID: 175989 [Multi-domain]  Cd Length: 127  Bit Score: 39.63  E-value: 3.08e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1579 LFIMVMHIKDLMSNDGADP-NPYVKTYLLpdphkTSKRKTKIARKTRNPTFNEMLVYSGYSKETLKQRELQLSVLSAESL 1657
Cdd:cd04022      2 LVVEVVDAQDLMPKDGQGSsSAYVELDFD-----GQKKRTRTKPKDLNPVWNEKLVFNVSDPSRLSNLVLEVYVYNDRRS 76

                           90       100       110
                   ....*....|....*....|....*....|
gi 1207137159 1658 -RENCYLGGITLCLKDF-DLSRETVKWYKL 1685
Cdd:cd04022     77 gRRRSFLGRVRISGTSFvPPSEAVVQRYPL 106
PX_SNX25 cd06878
The phosphoinositide binding Phox Homology domain of Sorting Nexin 25; The PX domain is a ...
 1443-1535 6.05e-03

The phosphoinositide binding Phox Homology domain of Sorting Nexin 25; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. The function of SNX25 is not yet known. It has been found in exosomes from human malignant pleural effusions. SNX25 shows the same domain architecture as SNX13 and SNX14, containing an N-terminal PXA domain, a regulator of G protein signaling (RGS) domain, a PX domain, and a C-terminal domain that is conserved in some SNXs.


Pssm-ID: 132788  Cd Length: 127  Bit Score: 38.51  E-value: 6.05e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1443 HYTYVIRILREGQSEPQ------FVFRTFDEFQELHNKLTILFQlW----KLPGfPSKMVLGRTHiKDVASKRKVELNSY 1512
Cdd:cd06878     28 LYVIVVHVSEVGLNEDEsissgwVVTRKLSEFHDLHRKLKECSS-WlkkvELPS-LSKKWFKSID-KKFLDKSKNQLQKY 104

                           90       100
                   ....*....|....*....|...
gi 1207137159 1513 VHNLMRSSTeVAQCDLIYTFFHP 1535
Cdd:cd06878    105 LQFILEDET-LCQSEALYSFLSP 126
PX_SNX16 cd07276
The phosphoinositide binding Phox Homology domain of Sorting Nexin 16; The PX domain is a ...
 1446-1533 6.72e-03

The phosphoinositide binding Phox Homology domain of Sorting Nexin 16; The PX domain is a phosphoinositide (PI) binding module present in many proteins with diverse functions. Sorting nexins (SNXs) make up the largest group among PX domain containing proteins. They are involved in regulating membrane traffic and protein sorting in the endosomal system. The PX domain of SNXs binds PIs and targets the protein to PI-enriched membranes. SNXs differ from each other in PI-binding specificity and affinity, and the presence of other protein-protein interaction domains, which help determine subcellular localization and specific function in the endocytic pathway. SNX16 contains a central PX domain followed by a coiled-coil region. SNX16 is localized in early and recycling endosomes through the binding of its PX domain to phosphatidylinositol-3-phosphate (PI3P). It plays a role in epidermal growth factor (EGF) signaling by regulating EGF receptor membrane trafficking.


Pssm-ID: 132809  Cd Length: 110  Bit Score: 38.16  E-value: 6.72e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1207137159 1446 YVIRILREGQsEPQFVFRTFDEFQELHNKLTILFqlwklPGF----PSKMVLGRTHIKDVASKRKVELNSYVHNLMRSSt 1521
Cdd:cd07276     23 YKIRVENKVG-DSWFVFRRYTDFVRLNDKLKQMF-----PGFrlslPPKRWFKDNFDPDFLEERQLGLQAFVNNIMAHK- 95

                           90
                   ....*....|..
gi 1207137159 1522 EVAQCDLIYTFF 1533
Cdd:cd07276     96 DIAKCKLVREFF 107
C2B_Ferlin cd04011
C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and ...
 1598-1664 9.49e-03

C2 domain second repeat in Ferlin; Ferlins are involved in vesicle fusion events. Ferlins and other proteins, such as Synaptotagmins, are implicated in facilitating the fusion process when cell membranes fuse together. There are six known human Ferlins: Dysferlin (Fer1L1), Otoferlin (Fer1L2), Myoferlin (Fer1L3), Fer1L4, Fer1L5, and Fer1L6. Defects in these genes can lead to a wide range of diseases including muscular dystrophy (dysferlin), deafness (otoferlin), and infertility (fer-1, fertilization factor-1). Structurally they have 6 tandem C2 domains, designated as (C2A-C2F) and a single C-terminal transmembrane domain, though there is a new study that disputes this and claims that there are actually 7 tandem C2 domains with another C2 domain inserted between C2D and C2E. In a subset of them (Dysferlin, Myoferlin, and Fer1) there is an additional conserved domain called DysF. C2 domains fold into an 8-standed beta-sandwich that can adopt 2 structural arrangements: Type I and Type II, distinguished by a circular permutation involving their N- and C-terminal beta strands. Many C2 domains are Ca2+-dependent membrane-targeting modules that bind a wide variety of substances including bind phospholipids, inositol polyphosphates, and intracellular proteins. Most C2 domain proteins are either signal transduction enzymes that contain a single C2 domain, such as protein kinase C, or membrane trafficking proteins which contain at least two C2 domains, such as synaptotagmin 1. However, there are a few exceptions to this including RIM isoforms and some splice variants of piccolo/aczonin and intersectin which only have a single C2 domain. C2 domains with a calcium binding region have negatively charged residues, primarily aspartates, that serve as ligands for calcium ions. This cd contains the second C2 repeat, C2B, and has a type-II topology.


Pssm-ID: 175978 [Multi-domain]  Cd Length: 111  Bit Score: 37.56  E-value: 9.49e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1207137159 1598 NPYVKTYLLPDphktsKRKTKIARKTRNPTFNEMLVYSGY-SKETLKQRELQLSVLSAESLRENCYLG 1664
Cdd:cd04011     22 DPVVKVEVGGQ-----KKYTSVKKGTNCPFYNEYFFFNFHeSPDELFDKIIKISVYDSRSLRSDTLIG 84
 
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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