Conserved Protein Domain Family
C2A_PI3K_class_II

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cd04012: C2A_PI3K_class_II 
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.
Statistics
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PSSM-Id: 175979
View PSSM: cd04012
Aligned: 24 rows
Threshold Bit Score: 115.148
Threshold Setting Gi: 189541561
Created: 11-Jan-2005
Updated: 2-Oct-2020
Structure
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Aligned Rows:
PubMed ReferencesClick to see Conserved Features Help

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
NP_001128289  679 KEArtsPDHLQFTIFAAHGIPTGWvscfEKYYLVCSLIHNGKDK--FKPVQSKKVGTYKSFf-----yLVKWDELIIFPI 751  western clawe...
O70173        535 RDHaglHSHLSFTVCSLHNVPETWahsyKAFSFSCWLTYAGKKL--CQVKSCRSLPVTKSFs-----fSVNWNEIINFPL 607  Norway rat
XP_002168892  308 IDPrtlTDNFSIRIMSVHRIPSNWksefTEFELEVSLYYGGKLL--CPKRKCSPCNIVYGFf-----dHLKVCEVIELEI 380  green hydra
CAA63485      844 IPIscvSKPIVVCISCLHRPLPNWk--fDDYSLCVQIVYGTRLLskPNVLTCSNDTSGGLFp------RLNFSAWLTFDQ 915  fruit fly
XP_002423453  353 KSIlefQDTILVNIGSLHRLQPTWt--hTAYVVSAQIYYGARAIkeTSICLTDVAKTSTSFy-----nRVVFDSWLNLKG 425  human body louse
XP_002404927  291 RRTvdaNELFSPKVEMLVQLQKAWvq-nYDSYSVDCALTYGERL--FSYQTTRRLYVTQRIf-----qCVNFDEYISFKN 362  black-legged ...
XP_396869     652 LISsevLDTILVRVGALHRLPGSWk--hDDYIIAAQIFHGTRPV--GTPVLSEPMAVSSNFy-----pRILFNAWLEFRG 722  honey bee
XP_001237042  933 ISIcniSQAVMVNVSCLHRPPLHWr--hDEYNLGVQIYHGARYI--SEPYVVQCSNELSGIy-----pRLTFNSWIMFRN 1003 Anopheles gam...
XP_001748498  589 VEVtnvEECLCITVSALHRLPLLWqqrhHHFRAEVSIYCGGTLL--SPSISIATTKSNSTLdfatwfeTIFFTETSTLEM 666  Monosiga brev...
XP_001952370  649 LSSk-vPDNVVIYVSCLHRLFSSWs--hDEYLIAAQIYHGTRPI--GNTVLSKAVIAEHSIy-----kRVVFESWLEFEN 718  pea aphid
NP_001128289  752 Qisql--plesILQLTLYGILnpnsggspd-----------ankqrkgpEMLGRVSLPLFtfrrMLIGGTKLLHLWtsfh 818  western clawe...
O70173        608 Eiksl--presMLVIKLFGIDsat----------------------hsaNLLAWTCLPLFpk-eKSPLGSRLLSMTlqse 662  Norway rat
XP_002168892  381 Avkqi--preaKVAISLFGCNqpkrs-------------------sdgkTMLGWVSANVYdyqgFLLSGSKLLGLLsnve 439  green hydra
CAA63485      916 Hpictl-preaRLTFVLYGKQaasegepnad---------qngerrqvtTELGWCSIQLFdfkrVMICGPYLLSLWppmt 985  fruit fly
XP_002423453  426 Vtiacl-presRLVLTLYGLTllppdheqsk--------anpgqpqyeqIELGWSAIQFFnyegKLTQGSFLLSLWppia 496  human body louse
XP_002404927  363 Iqirsl-pretRMYLTVVGHRdg------------------------adHVLGWTGLNIFadreHFNGGEFLLGLWspe- 416  black-legged ...
XP_396869     723 Isvcqv-preaRLVLVLYGRTlqptehesn----------ssaenimqkEELGWGAIQFFdyegIMSQGSFFLSLWpaia 791  honey bee
XP_001237042 1004 Pvctl--preaRLVVVLYGCVrepvdgggtsdgapgvndpggsegrmtkVELGWSSLQFFdferKMVQGSYLLPMWpptt 1081 Anopheles gam...
XP_001748498  667 KtplkqlpkesRIVIQLLASTadri---------------------mtwDPLGWVALRVYdhrgRLNSGWHLLGLWlepq 725  Monosiga brev...
XP_001952370  719 Mslcll-presRLVLVVYGRTfntegqd--------------tsatvsqTELGWGSIQFFnvegEFSQGKHLLSLWppca 783  pea aphid
NP_001128289  819 tgpapagt-----------trktnqmqrivlQVDFPLPAFDIVYI 852  western clawed frog
O70173        663 ppiemmapg----------vwdgsqptpltlQIDFPAATWEYVKP 697  Norway rat
XP_002168892  440 fnpvaica-----------tnniehretvivKIDFQAYHTEVIFP 473  green hydra
CAA63485      986 dkmlgpapargchpqpdfcpvlsievppyggRIEFPEHQEVPKPA 1030 fruit fly
XP_002423453  497 nkrfspapv----------pgthplqnhsvlYINLPYYGGTVEFP 531  human body louse
XP_002404927  417 -----------------------------mlSTRGPVSASEQNKG 432  black-legged tick
XP_396869     792 dkrlgpapa---------pgihphgdthaiiGVELPDYGGRVLFP 827  honey bee
XP_001237042 1082 dkffgpaps---------kgtypiggsfpilSIEIPSYGGAVVFP 1117 Anopheles gambiae str. PEST
XP_001748498  726 pnpt-------------------gtcgnnlyAPDSPSIMVRLGPD 751  Monosiga brevicollis MX1
XP_001952370  784 dkrlgpapa---------pgthpyshshpvlSIEIQEFDFKILFP 819  pea aphid
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