2RD0,3HHM,3HIZ


Conserved Protein Domain Family
C2_PI3K_class_I_alpha

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cd08398: C2_PI3K_class_I_alpha 
Click on image for an interactive view with Cn3D
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.
Statistics
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PSSM-Id: 176043
View PSSM: cd08398
Aligned: 9 rows
Threshold Bit Score: 278.213
Threshold Setting Gi: 170595983
Created: 12-Oct-2009
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
p110alpha-p85..
Conserved site includes 9 residues -Click on image for an interactive view with Cn3D
Feature 1:p110alpha-p85alpha complex
Evidence:
  • Structure:2RDO; Human p110alpha and a polypeptide containing the p110alpha-binding domains of p85alpha, contacts calculated at 3.5A
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                             ##                                                          
2RD0_A        353 KSLWVINSALRIKILCATYVNVnirDIDKIYVRTGIYHGgepLCDNVNTQRVpc-sNPRWNEWLNYDIYipdlpraaRLC 431  human
3HHM_A        348 KSLWVINSALRIKILCATYVNVnirDIDKIYVRTGIYHGgepLCDNVNTQRVpc-sNPRWNEWLNYDIYipdlpraaRLC 426  human
3HIZ_A        353 KSLWVINSALRIKILCATYVNVnirDIDKIYVRTGIYHGgepLCDNVNTQRVpc-sNPRWNEWLNYDIYipdlpraaRLC 431  human
AAF15300      242 KSLWAINSTLRIKILWATYVNVtirDIDKIYVRTGIYHGvepLCDNVNTQRVpc-sNPRWNEWLLYDMFipdlpraaRVC 320  African clawe...
CAF97548      325 KALWTINGSLRIKILCATYVNVnirDIDKIYVRTGIYHGgeqLCDNVNTQRVpc-sNPRWNEWLSYDMYipdvpraaRLC 403  spotted green...
NP_001004410  325 KSLWTINSALRIRILCATYVNVnirDIDKIYVRTGIYHGgepLCDNVNTQRVpc-sNPRWNEWLSYDMYipdlpraaRLC 403  chicken
XP_001181136   50 SCVWEVEENLRVKINFATYVNVk--ELDKIYVRTGIYHGeepLCPIVSTEQVpw-sNPRWNEWLTYDIKvndiprsaRWC 126  purple urchin
XP_001902593  189 CSLWKVDDNLKLRIHSASHLSIl--DFDKIYVKASLYHGi-dLIANRESACVspsnPRWSDGWIDFDVHlkdlapsvQLC 265  agent of lymp...
XP_002602300  323 RCIYDIQSPLRIKILCATYVNVk--EHDKIYVRSGVYHGgepLCTPVNTNRVqc-sNPLWTEWLEYEIMipdiprsaRLC 399  Florida lancelet
Feature 1               #                                    #### #                #              
2RD0_A        432 LSICSVKgrkgakeehCPLAWGNINLFdytdTLVSGKMALNLWPVPHGLEDLLNPigvtgsNPNKETPCLELEFDWFSSV 511  human
3HHM_A        427 LSICSVKgrkgakeehCPLAWGNINLFdytdTLVSGKMALNLWPVPHGLEDLLNPigvtgsNPNKETPCLELEFDWFSSV 506  human
3HIZ_A        432 LSICSVKgrkgakeehCPLAWGNINLFdytdTLVSGKMALNLWPVPHGLEDLLNPigvtgsNPNKETPCLELEFDWFSSV 511  human
AAF15300      321 LSICSVKgrkgakeehCPLAWGNINLFdytdTLVSGKMALNLWPVPHGLEDLLNPigvsgsNPNKETPCLELEFDCFSSP 400  African clawe...
CAF97548      404 LSICSVKgrkgakeehCPLAWGNINMFdythTLVAGKMALNLWPVPHGLEDLLNPigvtgsNPNKETPCLELEFEHFGCP 483  spotted green...
NP_001004410  404 LSICSVKgrkgakeehCPLAWGNINMFdytdTLVSGKMALNLWAVPHGLEDLLNPigvtgsNPNKETPCLELEFDWFSNP 483  chicken
XP_001181136  127 VSICSSEkrkgkkeggFAIPWGNINLFdfttRLQMANMRLYLWPPPKGNDDLLNPfgqtgpNPNKDAPCLELEFYRYPHS 206  purple urchin
XP_001902593  266 LSLVAVKqkkk--eeySGIGWVNIRLFdcdeKLIQGKFMLYLWPFPKYCTELLYPsgqvgsNDNHDTVRIEVEFEDYGCV 343  agent of lymp...
XP_002602300  400 LSICSVNrkkgkkedhCCLAWGNINLFdyqgNLQNGKYQLNMWSVPHGMDDLLNPigstgsNPSKDTPCLDLEFDRFAHV 479  Florida lancelet
Feature 1          
2RD0_A        512 V 512  human
3HHM_A        507 V 507  human
3HIZ_A        512 V 512  human
AAF15300      401 V 401  African clawed frog
CAF97548      484 V 484  spotted green pufferfish
NP_001004410  484 V 484  chicken
XP_001181136  207 L 207  purple urchin
XP_001902593  344 E 344  agent of lymphatic filariasis
XP_002602300  480 V 480  Florida lancelet

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