Conserved Protein Domain Family
C2_Freud-1

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cd08690: C2_Freud-1 
C2 domain found in 5' repressor element under dual repression binding protein-1 (Freud-1)
Freud-1 is a novel calcium-regulated repressor that negatively regulates basal 5-HT1A receptor expression in neurons. It may also play a role in the altered regulation of 5-HT1A receptors associated with anxiety or major depression. Freud-1 contains two DM-14 basic repeats, a helix-loop-helix DNA binding domain, and a C2 domain. The Freud-1 C2 domain is thought to be calcium insensitive and it lacks several acidic residues that mediate calcium binding of the PKC C2 domain. In addition, it contains a poly-basic insert that is not present in calcium-dependent C2 domains and may function as 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-II topology.
Statistics
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PSSM-Id: 176072
View PSSM: cd08690
Aligned: 14 rows
Threshold Bit Score: 229.886
Threshold Setting Gi: 221129069
Created: 23-Mar-2010
Updated: 2-Oct-2020
Structure
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Aligned Rows:
 
putative Ca2+
Feature 1:putative Ca2+ binding pocket [ion binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                                      #                                                 
NP_493412    632 DDVIELTIVSCRdvp-----lpSGYETHHANLFIKYTFpavvndlPQTGKTKLIAGTASPDFGESIMLNIgsGKSRNskL 706  nematode
XP_001901159 602 ENHIELTIMKIIeak-----lpAGWKASDGYLFVKYNFsfp-hdaHQTGRTKVIAATNSPEYNQKFLLTI--NRKTKq-L 672  agent of lymph...
NP_609488    661 LTDSELEIVVVRgi------syNVANPKDVDTYVRVEFpll-ndeSFKTKTNVIRDTSSPDYDERFKVDI--QRTNRq-F 730  fruit fly
CAN88230     626 LSSTDMVVVIVKgmnl---papSGVATNDLDAYVKFDFpypsseqPQKHKTAVVKNTNNPEYNQSFKLNI--NRNHRg-F 699  zebrafish
XP_001633387 629 DSHVEITIVRCLnip-----lpSGYSQKDLHCYVTYEFpypssedPQSGRTQTIKHTINPEYNEAFKVNI--DRKNRa-L 700  starlet sea an...
XP_001235393 716 LNSTEMHLLIVRginl---papPGVAPKDLDAFVKFEFhypsteqPQKSKTPVISNNNCPEYNQLFKLNI--NRNHRg-F 789  chicken
EFA03599     623 ENDLELTIVRGIs--------yTCSNPKEIDTYVKFDFpyp-qdePFSQRTATVKDTNSPEYNATYTIPI--QRNARv-C 690  red flour beetle
XP_002432574 415 DNELELTIMQGIn--------yKVSNPNDVDTYVTYEFpyp-nssPPSGRTSTVKNTNNPVYNTRLTFPI--NREASa-C 482  human body louse
NP_001079953 700 LSSTEMLLIIVRginl---papSGVAPNDLDAYVKFEFpypsseqPQKNKTLVIKNTNSPEYEQSFKLNI--NRNHRg-F 773  African clawed...
XP_002400067 643 VRAINLPGRSFGtngsiacgcrCGRKPDELDSYVRVEFpfp-ndaPQSVRTRTVKDTINPEFQETFKFEI--NRKSRs-F 718  black-legged tick
Feature 1                      # #      #  #                                                     
NP_493412    707 QRTFKRGGLKFEVFQKGGFm-rSDKLLGTCEWKLEKLEHSAEMEESLPl---KDGRKAVGGLLSAKVRIRQPigdakAQH 782  nematode
XP_001901159 673 QRVIKRNCLKFEIYQKGGFl-rSDKLIATADCKLIDLEEKVCIHKSIDl---MDGRKQTGGKLIYQVRVREPlsgkkLLM 748  agent of lymph...
NP_609488    731 QRIFKRHGVKFEIYSRGGFl-rSDTLIGTVNVKLQPLETKCEIHDTYDl---MDGRKQVGGKLEVKIRVRNPiltkqMEH 806  fruit fly
CAN88230     700 RRVIQSKGLKLEVLHKGGFl-rSDKPVGSAQIKLEKLEAQSEVREIVEl---MDGRKATGGRLEVRVRLREPlggqeLQT 775  zebrafish
XP_001633387 701 PRIFRRQALKFEIKYERGFl-kGDKALGQAQVKLAPLDSKSEIHDCVDlmdsDRGRRAVGGKVEVIIRVREPltdkdVSI 779  starlet sea an...
XP_001235393 790 RRAIRSKGIKFEVYHKGSFf-rSDKHVGTAHLKLDKLESECEVREIIEi---FDGRKPTGGKLEVKVRLREPlsgqdLQT 865  chicken
EFA03599     691 QRVFKRQSVKFEVYSKGGFf-rGDTLIGTATVKLQPLETQCELHDSFDl---LEGRKKIGGKLEVRMRLRHPivnqqVEQ 766  red flour beetle
XP_002432574 483 QRVFKRHGIKMEVWSKGGFf-hRDSSLGTVVVKLMPLGKDIKIHEAFDl---MNGRRPAGGKLEVKVRIRDPiagkkMEK 558  human body louse
NP_001079953 774 KRVIQTKGIKFEIFHKGFFlvrSDKQVGSASVKLDKLETQCEIREIVEv---FDGRKPTGGKLEIKVRLRDPlngqdLQV 850  African clawed...
XP_002400067 719 ARITKRHPIKLEVWAKRGFl-rSDAILGTVAVKFEDLETKCDLHDSYDv---FDSKRPSGGKLEVKVRVREPfvskqVEE 794  black-legged tick
Feature 1                
NP_493412    783 IAQKWLIL 790  nematode
XP_001901159 749 MQKKWLIL 756  agent of lymphatic filariasis
NP_609488    807 ITEKWLVL 814  fruit fly
CAN88230     776 VTERWVVL 783  zebrafish
XP_001633387 780 EKWKWLVI 787  starlet sea anemone
XP_001235393 866 VTENWLVL 873  chicken
EFA03599     767 LHEKWLVI 774  red flour beetle
XP_002432574 559 VTERWLII 566  human body louse
NP_001079953 851 VTEKWLVM 858  African clawed frog
XP_002400067 795 IKQRWLII 802  black-legged tick

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