Conserved Protein Domain Family

cd08680: C2_Kibra 
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C2 domain found in Human protein Kibra
Kibra is thought to be a regulator of the Salvador (Sav)/Warts (Wts)/Hippo (Hpo) (SWH) signaling network, which limits tissue growth by inhibiting cell proliferation and promoting apoptosis. The core of the pathway consists of a MST and LATS family kinase cascade that ultimately phosphorylates and inactivates the YAP/Yorkie (Yki) transcription coactivator. The FERM domain proteins Merlin (Mer) and Expanded (Ex) are part of the upstream regulation controlling pathway mechanism. Kibra colocalizes and associates with Mer and Ex and is thought to transduce an extracellular signal via the SWH network. The apical scaffold machinery that contains Hpo, Wts, and Ex recruits Yki to the apical membrane facilitating its inhibitory phosphorlyation by Wts. Since Kibra associates with Ex and is apically located it is hypothesized that KIBRA is part of the scaffold, helps in the Hpo/Wts complex, and helps recruit Yki for inactivation that promotes SWH pathway activity. Kibra contains two amino-terminal WW domains, an internal C2-like domain, and a carboxy-terminal glutamic acid-rich stretch. 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: 176062
View PSSM: cd08680
Aligned: 22 rows
Threshold Bit Score: 155.467
Threshold Setting Gi: 47209418
Created: 23-Mar-2010
Updated: 2-Oct-2020
Aligned Rows:
PubMed ReferencesClick to see Conserved Features Help

Sequence Alignment
Format: Row Display: Color Bits: Type Selection:
2Z0U_A         30 TRIQIALKYDEknkqFAILIIQLsnlsal---lqqqdQKVNIRVAVLPcses-ttcLFRTRPLDasdTLVFNEVFWVSxs 105  human
XP_002598149  665 AQVQVGLKYNFtegqLSIRVEQIrnlsal---nveqgNQICVRAALLPcppn-anfTFATKPTCdlaNPVFNEVFALPvm 740  Florida lancelet
XP_001603098  651 AQVQIKLRYSIsdglLHIGIERArnlaal---yipdsMQVYIKVALLPmqap-vnqVCCTKPVIdmrKPTFGETFPIAvp 726  jewel wasp
EFA02411      874 AQVQIKLRYASgesiLNVGVERArnlgal---yiaenAQVFVKIALLPsgts-tpsVYCTKCVKdlkKPSFGDVFNISvp 949  red flour beetle
XP_001946853  586 SQVQIRLRYSIaeqvLHVCIERLrnvval---siaesWQLYIKIVLLPsnsn-tslSGCTKPISdlsKPRFGDSFAFNlp 661  pea aphid
XP_001618378   56 AQIKIGLSYDTdleaLLVSIEQGknlkelqgreapecIAINVKLQLLPgd----gvIMETNLSNdldNPTYGEQFHIPlp 131  starlet sea a...
XP_002163573  655 AQVCVGLEYENn--kLIISVEKGrhfral---yfknyKYVFVRGRLLPsnn---llQFRTIRSNvsdEQNFHEQFSFKid 726  green hydra
NP_001034055  693 AQVQIGLKYLKqegvLVVSLERAnnllalw-tasadnSQVYLRAALLPns----ltSIRTKALGdfqKPVFNDTFAVPit 767  fruit fly
CAF93108      628 PQVRLGLLWDSgsqsLRLHLLQLkglnrw---ivrdgHKVYVKVHLVPldasracaFYCCTALEpqcQMSFNEGFCIPva 704  spotted green...
XP_001869112  573 AQIQISIRYTAtdstLCITIERGrnlaal---clpegCQLFVRAILLPgta---tpFIRTNAVTdfvKPVFKTMLVAQmp 646  southern hous...
2Z0U_A        106 ypalhqkTLRVDVCTTDrs-hLEECLGGAQISLaev--crsGERSTRWYNL 153  human
XP_002598149  741 entlytkTLQMHIWALGse-qEEDCLGCAQISLadfdatcgPAGTVRWYNL 790  Florida lancelet
XP_001603098  727 lnklytkTLQVNVWCTSg--eSEECLGSAQVSLadf---spETPSVKWYNI 772  jewel wasp
EFA02411      950 ankiytkTLQLNVWSKTe--eQEKCVGCAQVSLadf---nvQQVSQKWYNI 995  red flour beetle
XP_001946853  662 snklctkTLQVNVWGLGpd-dITECLACAQVSLaefn-eteNNSWCKWYNL 710  pea aphid
XP_001618378  132 esklvckTLQVHVWAVTky-kTEELLGGSQISLaef--dtqSPIRFRWYNL 179  starlet sea anemone
XP_002163573  727 rtklsnkTLQLDLCGNLddiaTEECLGGVQISLadf--dsnECIVMKWYNL 775  green hydra
NP_001034055  768 ldklltkSLQVTVVTMTg--qKEEIIGTVQISMaef---npEDSTLKWYNV 813  fruit fly
CAF93108      705 aaplaacALQLSVCSLGpa-aQEELLGTAQVSLadc--egsAEMVYQWLRV 752  spotted green pufferfish
XP_001869112  647 lekvytkSLHVKVMIIVg--qREDWVGSAQISLaef---naADASNKWYNI 692  southern house mosquito
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