Conserved Protein Domain Family
C2A_Munc13-like

?
cd08676: C2A_Munc13-like 
C2 domain first 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 second C2 repeat, C2B, and has a type-II topology.
Statistics
?
PSSM-Id: 176058
View PSSM: cd08676
Aligned: 13 rows
Threshold Bit Score: 162.541
Threshold Setting Gi: 198433362
Created: 24-Mar-2010
Updated: 2-Oct-2020
Structure
?
Aligned Rows:
 
putative Ca2+
Feature 1:putative Ca2+ binding site [ion binding site]
Evidence:

Sequence Alignment
?
Format: Row Display: Color Bits: Type Selection:
Feature 1                                                     #     #                             
BAG61353      133 YLQQVFGTSLEEHTEAIERvrkak-aptyaLKVSVMRAknllaKDPNGFSDPYCMLGIlpasdatrepraqkeqr----- 206  human
CAG12218       70 YCLQVFDMGEEEHEIILQKvqeak-rasfsLRVSVMKAknlmaKDANGYSDPYCMLGIlvgqspremeekkerkfsfr-- 146  spotted green...
XP_415627      64 YVQKAFGMDAEEHRAIMQQvqele-spifcLKATVKEAkgilgKDVSGFSDPYCLLGIesknqepahpdskr-------- 134  chicken
NP_001133321  101 YIREAFSMAEDEHQSLTDRvqnte-ppvycLMATVKEAkgilgKDVSGFSDPYCLLTIledekesktrrsrpk------- 172  Atlantic salmon
B2RUP2         83 YLQEAFQVQPEEHQQMLRRvrele-kpvfcLKATVKQAkgilgKDVSGFSDPYCLLGIeqkvgvaegspvsrr------- 154  house mouse
XP_001185038  779 YAQETLNVNPQEHEALLERvsnsl-ppaliMVVDVISAkgllaKDSNGLSDPFCVLGIvalwrentseggkhkm------ 851  purple urchin
XP_002125578   66 LAQDTFEVSNSSHKVAVEKarsqeiskkcvLRLQVIKAehlaaKDVDGTSDPYCLLGVvpasqyvn-------------- 131  Ciona intesti...
XP_002435694   73 YAQRAFNMPPESHRRLLALareek-ppipvLNVTVVEAqgleaKDPNGFSDPYCMLGIqpasprrslrklgasfkk---- 147  black-legged ...
NP_001024712   76 YVRNAFQGDAAVHNALMEKakqnk-ppsvlLNILLLEAkdliaKDVNGFSDPFAMMGVvpgtrkenqpmtdsahpekeeq 154  nematode
XP_002162220  133 YGKQVFGISASEHKTIYDEvs--------kLKVMIGAAgl-dpKDANGFSDPYCMISVidigegdvkdkskk-------- 195  green hydra
XP_002577726  402 YVKNVFDLPTKIYDDLRMEacqae-ppvvvLNVSVIEAknleaKDLNGFSDPYCILGIifgryvgnneksttpdlsintt 480  Schistosoma m...
NP_001120507   98 YLQKAFNMDPGEHEAILQRvrgle-apircLKVTVKEAkgilgKDVSGFSDPYCLLGIdhrssgrsrdsspdrk------ 170  western clawe...
NP_648096     319 HAQRAFGVNPDRHYRLLHAsaedk-pkiivLSAVVIEAdgleaKDANGFSDPYCMLGIqpdenggppvsplplpptpral 397  fruit fly
Feature 1                                                                                         
BAG61353      207 ------------------------------------------------------------------fgfrkgskrggplp 220  human
CAG12218      147 ---------------------------------------------------------------krkeklekrsstkevlp 163  spotted green...
XP_415627     135 ---------------------------------------------------------------------rlkavvkdlip 145  chicken
NP_001133321  173 ---------------------------------------------------------------------prkavvkdavs 183  Atlantic salmon
B2RUP2        155 ---------------------------------------------------------------------rqkavvkhtip 165  house mouse
XP_001185038  852 -------------------------------------------------------------------shsrhdllldhas 864  purple urchin
XP_002125578  132 ----------------------------------------------------------------------------lrss 135  Ciona intesti...
XP_002435694  148 ------------------------------------------------------------------keprsgslesatvp 161  black-legged ...
NP_001024712  155 eakspralhgk----------------------------------------kdglmhrfggsfrrkvgkkgkpqdtgtip 194  nematode
XP_002162220  196 ----------------------------------------------------------------------kkkvlrdfek 205  green hydra
XP_002577726  481 tttfspndletvqttrnvsgkkgfdnnrvtftrssfrrfsqsfnkrtnqseklnishnesfkmsgatssksvvnkeghvp 560  Schistosoma m...
NP_001120507  171 --------------------------------------------------------------------qkqkavvrntip 182  western clawe...
NP_648096     398 sadmsggfdnsatd----------------------------------spphrkhsfrlsfkrreagrreqrdslggpvp 443  fruit fly
Feature 1                                                  # #                                    
BAG61353      221 akcIQVTEVKSstlNPVWKEHFLFEiedv--stdQLHLDIWDHDddvslveacrklneviglkgtgr----------yfk 288  human
CAG12218      164 arsIQVTEVKPetlNPVWDEHFVFEiddv--nndLLHLDIWDHDddvsvaeackklnevsglrgmgr---------yfkq 232  spotted green...
XP_415627     146 edqIHRTQIISqtlNPVWDETFILEfedm--etaSFHLDMWDSDtvesvrhklgeltdlh-------------------- 203  chicken
NP_001133321  184 deeVYTTETKKqtlNPIWNQTFVLEfeet--agaSFHMEMWDRDeevslaqkleeirtnf-------------------- 241  Atlantic salmon
B2RUP2        166 eeeTHRTQVKSqtlNPVWDETFILEfedi--anaSFHLDMWDLDtvesvrqklgeltdlh-------------------- 223  house mouse
XP_001185038  865 kdsLCVTEVKEktlCPTWREQFRFDvgdv--nneQLQVEVCDVGdvnneqlqvevwdhdedssvgqlikknagdvsnlkg 942  purple urchin
XP_002125578  136 ktvTANTSVINstlTPEWNETLELFvereqisnsNLQIQVWDSDevvggngnlkkvkgvkgv------------------ 197  Ciona intesti...
XP_002435694  162 akfIRTTTVKPatlNPRWNERFRLDidd----vhADRLPSMDHDdessvfdaarklnevtglkg---------------l 222  black-legged ...
NP_001024712  195 aklIKASSVQKktlNPKWSEKFQFTvedv--qrdQFHIDIWDHDdeeqsvldavsslnqitggfk-------------gi 259  nematode
XP_002162220  206 eedIKLTKIKLktlHPEWNQHFKFVvndv--knqVLRVDIWDKDdntvvwdsnnaitaikgvkg---------------- 267  green hydra
XP_002577726  561 vgiMKSTQVKEqtlNPVWNENFRLElddi--ssdKLHLDIWDHDeetsvleavrslneirgvkq---------------l 623  Schistosoma m...
NP_001120507  183 edrMHRTQIIGqtlNPVWNETFILEiedm--ekaSFQMDMWDSDdvetvrtklgdltdlh-------------------- 240  western clawe...
NP_648096     444 aklIKATSIKPhtlTPKWNEKFKFDiddi--ntdTFHLDIWDHDdescvmdavsrlnevrgvr----------------- 504  fruit fly
Feature 1                                                                                 
BAG61353      289 qivksarangtagptedhtDDFLGCLNIPVrrdtamsqrgrsgflshllllshllrlehsaegpnsSSWRGE 360  human
CAG12218      233 iaksvrangstssgseenaDDFLGCINIPLnvsvlpqsepkprvpla---sppaifffqempvggyDTWFKL 301  spotted green pufferfish
XP_415627     204 ----glkrifkdarkdkgqDDFLGNVVLRLkdlh-----------------------------cwdDQWYQL 242  chicken
NP_001133321  242 ---hglrrmikdakklkgqDDFLGNIVLRLkdlh-----------------------------cteDNWYVL 281  Atlantic salmon
B2RUP2        224 ----glrrifkearkdkgqDDFLGNVVLRLqdlr-----------------------------creDQWFPL 262  house mouse
XP_001185038  943 mgrffkeiaqsakkdgknlDDFLGWVTIPLntis----------------------------sqglECSFPL 986  purple urchin
XP_002125578  198 --gryvkevaqsvtksedhDDFMGFSSLPLssvp----------------------------sqglERWFKL 239  Ciona intestinalis
XP_002435694  223 gryfkqiaqsaraspvdtvDDFLGCVNVALgv---------------------------------mDRWLPL 261  black-legged tick
NP_001024712  260 gryfkevtqsaransddctDDFLGCINMKLaeip----------------------------pdglEQWFTL 303  nematode
XP_002162220  268 agrflremyqsarspdsflDDFMGLVEIPLkslp----------------------------eeglDSWFQL 311  green hydra
XP_002577726  624 gryfkqvsqsarknqtgdmDDFLGCVTIDIkdip----------------------------stglDSWFKL 667  Schistosoma mansoni
NP_001120507  241 ----glkrifkearkdkgqDDFLGNVVLQLrglk-----------------------------ckeDCWYNL 279  western clawed frog
NP_648096     505 -glgrffkqvcqsarqgsqDDFLGSVNIPLseip----------------------------stglDAWFKL 547  fruit fly

| Disclaimer | Privacy statement | Accessibility |
NCBI Home NCBI Search NCBI SiteMap